ISSN:0069-3030    

DOI:10.1039/OC96865FX001

出版商:RSC    

年代:1968

数据来源: RSC

ISSN:0069-3030    

DOI:10.1039/OC96865BX003

出版商:RSC    

年代:1968

数据来源: RSC

摘要:

2 PHYSICAL METHODS Part (i) Mass Spectroscopy By John M. Wilson (Department of Chemistry The University of Manchester Manchester 13) DURING 1968 there has been a further increase in the number of papers on this topic in the chemical literature. A large number of these are concerned mostly with either simple descriptions of spectra or with necessarily speculative inter- pretations of fragmentation patterns of specific groups of organic compounds for reasons of space these cannot all be discussed here. The popular acceptance of orbital symmetry correlations in the explanation of photochemical and pyrolytic reaction mechanisms has led to their appli- cation to mass spectral problems. The early results look promising particularly with regard to problems of skeletal rearrangements.There is also a greater interest in a more detailed treatment of the kinetic aspects of mass spectro- metry which this reporter welcomes. General Methods of Interpretation.-A general approach involving correlation of molecular orbitals of the decomposing ion and the products has been sugges- ted.' According to this approach the butadiene ion should be formed in an excited state by the retro-Diels-Alder reaction on the cyclohexene molecular ion. The disadvantages of this approach are that it assumes a concerted process and that as yet only 7c orbitals are considered for ionisation. Decomposition of ions of the type (1)to produce (3) can go by a single-step process with elimina- tion of hydrogen when X = CH:CH (stilbene) or by a successive elimination of two hydrogen atoms when X = NH (diphenylamine).If this.difference is the r 1+. (1) (2) CO,Me R0- (3) (4) ' R.C. Dougherty J. Arner. Chern. SOC.,1968,90 pp. 5780 5788. John M. Wilson result of cis-and trans-arrangements of the hydrogen atoms in (2)then we have dis- and con-rotatory ring closures respectively which can only result from the excited states of the molecular ions.2 A different MO approach to mass spectra is used in the calculation of fragmentation probabilities in cyclic hydrocarbon^.^ In this case the authors make the assumption that the majority offragmentations take place within one vibration after impact a rather bold generalisation but the results are in accord with measured spectra.Much more detailed calculations have been carried out on the molecular ion of eth~lamine.~ The calculated potential-energy surface shows that it is much easier for the C-C bond vibra- tion to be transformed into a reaction co-ordinate than for the C-N.4 Previous studies of mass spectra which involved Hammett relationships have been criticised mainly on two grounds. If a molecular ion decomposes by metastable transitions the abundance measured at the collector may not be accurately ‘representative of ion concentrations in the ion source.’ The second objection is that the substituent affects not only the activation energy of the decomposition process but also the internal energy distribution in the decom- posing ion.6 Such effects can be seen in a study of the mass spectra of 4-phenyl-butyrates of the general type (4).’ The loss of a methoxy-radical from the mole- cular ion is decelerated by electron-donating substituents because of the in- creasing number of low-energy electronic states of the molecular ion below the fragmentation threshold.Such criticism does not imply any great restrictions on the value of such studies but shows that one must take all these factors into consideration in the interpreation of data.8 The spectra of ring-substituted anisoles exhibit two important primary processes the elimination of a methyl radical which is accelerated by electron-releasing substituents and the loss of formaldehyde which is decelerated by such sub~tituents.~ The results to- gether with metastable-ion data are in agreement with the proposal of the four-membered ring transition-state (5) for the latter process.The approach of Johnstone has been to use in the Hammett-plot activation energies rather R. A. W. Johnstone and S. D. Ward J. Chem. SOC.(C),1968,1805. K. Hiroto and Y. Niwa J. Phys. Chem. 1968,72 5. J. C. Lorquet A. J. Lorquet and J. C. Leclerc in ‘Advances in Mass Spectrometry’ vol. 4 ed. E. Kendrick Inst. Petroleum London 1968. I. Howe and D. H. Williams Chem. Comm. 1968,220;J. Chem. SOC.(B) 1968,1213. R. G. Cooks R. S. Ward I. Howe and D. H. Williams Chem. Comm. 1968 837. ’ D. G. I. Kingston and H. P. Tannenbaum Chem. Comm. 1968,444. * F. W. McLafferty Chem. Comm. 1968 957. F. W. McLafferty and M. M. Bursey J. Org. Chem. 1968,33 124.Mass Spectrometry than ion abundances.'O These are measured by taking the difference between the appearance potential of the fragment ion and the ionisation potential of the molecule and have the advantage that there are no complications due to the kinetics of the process and that since the method is comparative the usual errors in absolute appearance potential measurements are avoided. The plot for the process (6) -+ (7) gives different slopes for meta-and para-substituents suggesting that an excited state of the molecular ion is involved. There has also been some more detailed study of metastable-ion igtensities. Although in general the shape and intensity of peaks corresponding to decom- positions of the same ion from different sources are similar there are small differences which can be interpreted.The peak due to the transition C6H5CO+ -+ C6H5+ in the spectra of a series of substituted benzophenones has an in- tensity which varies with the internal energy distribution in the molecular ion.'' The same metastable peak in the spectra of compounds PhCOR with a wide variety of R-groups is similarly affected,12 particularly by the number of vibrational degrees of freedom in R reflecting its ability to remove excess energy from the molecular ion in the decomposition. The ions C12HloO+' in the mass spectra of diphenyl ether and diphenyl carbonate decompose at different rates. In the latter case the average internal energy of the molecular ion will be greater and the carbon dioxide molecule eliminated cannot remove much of the excess of energy.The ion formed therefore decomposes faster than the molecular ion of diphenyl ether although there is also the possibility that an intermediate (8) of different structure may be involved.' Similar behaviour lo R. A. W. Johnstone and D. W. Payling Chem. Comm. 1968. 601. 'I M. L. Gross and F. W. McLafferty Chem. Comm. 1968 254. R. G. Cooks and D. H. Williams Chem. Comm. 1968 627. l3 D. H. Williams. S. W. Tam. and R. G. Cooks. J. her. Chem. SOC.. 1968.90.2150. 10 John M. Wilson is found in the mass spectra of phenol phenetole and tropolone where a C,H,O'+' ion is found which is considered to have the phenol structure. The ion from tropolone decomposes faster than the molecular ion of phenol; in this case the neutral fragment is carbon monoxide.In the case of phenetole where the neutral fragment is ethylene the C6H,0+' ion decomposes more slowly than phenol because there is a high probability of the excess of vibrational energy being removed by eth~1ene.I~ The controversy centring round the concept of a fixed charge location con- tinues. Compound (9) does not undergo typical ketone fragmentations when R = NH,.15 as reported last year. This was taken as an indication that the positive charge was located in the arylamine ring and did not migrate to the other ring. In the compound (lo),however fragmentations of the acyl group can be observed when R = NH, and the behaviour of (9) is explained in terms of more favourable competing processes e.g.fission of the benzylic bond.16 It is reported however that the ion (11) in the mass spectra of some amino- steroids does not undergo elimination of acetic acid.I7 The implication here is that the charge cannot migrate from ring A to ring D. Fragmentation and Rearrangement Processes.-Last year's report of random hydrogen migrations in aromatic molecules' has been followed by similar studies of deuteriated systems. In furan and thiophen where elimination of C2H2 from the molecular ion can be observed scrambling of hydrogen and and deuterium atoms in the ion is incomplete i.e. fragmentation can compete with the randomisation proce~s.'~ In the elimination of HCN from the mole- cular ion of a-and P-cyanonaphthalenes randomisation over the two rings appears to be complete.20 In the mass spectrum of 2-deuteriothiazole elimina- tion of DCN takes place and is 98 % specific.In the case of the analogous benzo- thiazole the same process is 92% specific but the corresponding metastable ions show a random loss of HCN and DCN.20 In the spectra of tris-(2,4,6- trideuteriopheny1)phosphine and its oxide there are completely specific losses of a deuterium atom.21a There is therefore a hydrogen randomisation process which can take place in all aromatic systems but in order to be observed it must be able to compete kinetically with the fragmentation process which is being observed. In the mass spectrum of diphenylmethanol there is in addition a slow process of hydrogen exchange between the two aromatic Hydrogen scrambling processes can also be observed in the spectra of some ali- phatic compounds.The production of acyl ions from aliphatic ketones is a specific single-bond cleavage at high electron energies.22 In the spectrum of l4 D. H. Williams R. G. Cooks I. Howe J. Amer. Chem. SOC.,1968,90 6759. l5 T. J. Wachs and F. W. McLafferty. J. Amer. Chem. SOC.,1967,89 5054. l6 A. Mandelbaum and K. Biemann J. Amer. Chem. SOC. 1968,90,2975. I' H. Bruderer W. Richter and W. Vetter Helu. Chim. Acta 1967 50 1917. l* J. M. Wilson Ann. Reports (B),1967 64 59. l9 D. H. Williams R. G. Cooks J. Ronayne and S. W. Tam Tetrahedron Letters 1968 1777. R.G. Cooks I. Howe S. W. Tam and D. H. Williams J. Amer. Chem. SOC. 1968,90,4064. (a) D. H. Williams R. S. Ward and R. G.Cooks J. Amer. Chem. SOC. 1968 966; (b) D. H. Williams R. S. Ward and R. G. Cooks J. Chem. SOC.(B) 1968 522 22 M. Kraft and G. Spiteller Annalen 1968,712 28. Mass Spectrometry [2,2,4,4-2H4]octan-3-one the C6H ion contains two deuterium atoms at 70 ev but at 12 ev analogous ions containing three and four deuterium atoms appear.23 Such randomisation has been confirmed in the spectra of other deuteri- ated ketones.24 Random rearrangements are also common in the mass spectra of olefins. A study of ionisation potentials and appearance potentials of the isomeric methylcyclohexenes and methylenecyclohexane shows that although ground states of the molecular ions reflect the differences in structure most of the fragments appear to be formed from a common intermediate.25 An examination of the spectra of various deuteriated derivatives of 3-phenyl- propanol shows that prior to fragmentation an exchange of hydrogen atoms takes place between the hydroxy-group and the aromatic ring.26 An interesting long-range hydrogen migration takes place in the mass spectrum of the steroidal alkaloid (12).27One of the fragmentation processes leads to an ion for which the structure (13 ;R = H) has been suggested and this ion decomposes further by loss of amonia.If the compound is fully deuteriated on nitrogen the ion (13; R = 2H) is formed and this decomposes by loss of N2H3.The author suggests that this ion is formed after a process involving transfer of hydrogen atoms between two ions. The reason for this suggestion is the conceptual diffi- culty involved in envisaging a specific hydrogen transfer from the C-3 to the C-20 amino-group.Whether such an interionic process is allowed by simple electrostatic considerations is open to question. The question of ring expansion in aromatic systems continues to provoke discussion. The mass spectrum of [l,a-13C2] toluene has provided us with further information on the tropylium ion. In the decomposition C,H,+ + C5H5+the decomposing ion appears to have the 13Catoms randomly mixed with the I2C atoms.28 The simple picture in which the a-carbon atom is in- serted between C-1 and C-2 is not valid. This is in agreement with the original work of Meyerson on 2H labelled compounds.29 By using a method which 23 W. Carpenter A. M.Duftield and C. Djerassi J. Amer. Chem. SOC.,1968 90,160. 24 A. N. H. Yeo R. G. Cooks and D. H. Williams Chem. Comm. 1968 1269. 25 R. E. Winters and J. H. Collins J. Amer. Chem. SOC.,1968,90 1235. 26 N. M. M. Nibbering and Th. J. deBoer Tetrahedron 1968 1415. 27 P. Longevialle Chem. Comm. 1968 545. ’* K. L. Rinehart jun. A. C. Buchholtz G. F. Vanlear and H. L. Cantrill J. Amer. Chem. SOC. 1968,90,2983. 29 H. M. Grubb and S. Meyerson in ‘Mass Spectrometry of Organic Ions’ ed F. W. McLafferty Academic Press New York 1963. 12 John M. Wilson involves the examination of substituent effects at different electron energies,30" Brown has suggested that substituted toluenes may initially form a benzyl ion which later rearranges to tropyli~m.~~' He comes to a similar conclusion from an examination of Hammett plots of formation of substituted benzyl ions from substituted benzyl phenyl ethers.31 From deuterium labelling results on diphenylmethane it would appear that the C7H7+ ion produced from this molecule has a tropylium-ion structure and is formed without extensive randomisation of the hydrogen atoms taking place.In this respect it differs from the corresponding ion formed from biben~yl.~~ Djerassi has examined a series of N- and C-methyl derivatives of isoquinoline pyrrole and indole. The prominent process in the spectra of all these compounds is loss of a hydrogen atom from the methyl group followed by elimination of HCN.33 By I3C labelling he has shown that in the N-methyl compounds the + Me SiOSiMe N (14) (151 [M -HI + ion has not undergone ring expansion [e.g.(14) -+(15)]. The results in the C-methyl series are not unambiguous but are consistent with ring expan- sion. The elimination of HCN from the molecular ion of aniline takes place from an ion in which the carbon skeleton is the same as in the parent mole- ~~le.~~*~~ The same elimination takes place from the C6H6N+ fragment ion from aniline and the 13C labelling evidence suggests that this may have the azatropylium structure although the rearrangement may not be ~omplete.~ The same is true of the C,H,N+ ion from ~ulphanilimide.~~ Skeletal rearrangements of various types continue to be reported in large numbers. A number of trimethylsilyl ethers of glycols undergo rearrangements which produce the ion (16).36*37 It can be formed by long-range migrations as in the case of the trimethylsilyl ether of de~ane-l,lO-diol.~~ Other long-range migration processes have been observed in the spectra of trimethylsilyl ethers of aliphatic hydroxy-ester~.~~ Nevertheless these derivatives provide useful structural information.The simplest approach so far to the solution of the problem of the determination of double-bond positions in unsaturated hydro- carbons and esters is the process which entails oxidation with osmium tetroxide followed by trimethylsilylation of the glycol. In the spectrum of the bistrimethyl- silyl ether there are two abundant fragment ions which are formed by simple 30 P. Brown J. Amer. Chem. SOC.,1968,90 (a) p.4459; (b)p. 4461. 31 P. Brown J. Amer. Chem. SOC. 1968,90 2694. 32 S. Meyerson H. Hart and L. C. Leitch J. Amer. Chem. Soc. 1968,90 3419. 33 M. Marx and C. Djerassi J. Amer. Chem. SOC.,1968 90 678. 34 A. V. Robertson M. Marx and C. Djerassi Chem. Comm. 1968,414. 3s K. L. Rinehart jun. A. C. Buchholtz and G. E. VanLear J. Amer. Chem. SOC.,1968,90 1073. 36 J. Diekman J. B. Thomson and C. Djerassi J. Org. Chem. 1968,33,2271. 37 J. A. McCloskey R. N. Stillwell and A. M. Lawson Analyt. Chem. 1968,40,233. 38 W. J. Richter and A. L. Burlinghame Chem. Comm. 1968 1159. Mass Spectrometry 13 fission of the bond between the two oxygen-bearing carbon atoms.37*39 Interpretation of such spectra may sometimes be simplified by the use of deuterium labelling in the trimethylsilyl t.RL CO-N-C0-R3 I RZ (19) (17) Elimination of carbon dioxide from substituted maleimides is expected to proceed by initial rearrangement of the imide (17) to the isoimide (18). Calcula- tions suggest that an electronically excited state of the molecular ion may be in~olved.~' The interconversion is not thermal.41 Acyclic imides of the general formula (19) undergo carbon monoxide elimination from their molecular ions.42 A large number of skeletal rearrangements of ions can be described by the general scheme (20) +(21) 4(22).43 In this scheme the three-atom zc Z--c &z=c I +* II +.I or A-B A=B A~BA%B (20) (211 (22) group must have a p, orbital system and the migrating group Z must have either a pn orbital or a vacant p-orbital.A typical example is (6)+ (7). Some other migrations appear to take place by five-membered ring transition-states. Examples are the transition (23) 4 (24) detected by "0 labelling44 and the +S/CH2 \c + S=CH2 I %-I dI CH,-0 'R R (25) (26) 39 P. Capella and C. M. Zorzut A'nalyt. Chem. 1968,40 1458. 'O T. W. Bentley and R. A. W. Johnstone J. Chem. SOC.(C),1968,2354. '' C. M. Anderson R. N. Warrener and C. S. Barnes Chem. Cornm. 1968 166. '' C. Nolde S.-0. Lawesson J. H. Bowie and R. G. Cooks,Tetrahedron 1968 1051. 43 T. W. Bentley R. A. W. Johnstone and D. W. Payling Chem. Comm. 1968 1154. "T.H.Kinstle. 0.L. Chapman. and M. Sung J. her. Chem. Soc. 1968.90 1227. John M. Wilson elimination of carbon monoxide from ions in the spectrum of thioglycollic esters (25) -+ (26).45 Aryl migrations are found in the spectra of nitrone~~~ and azine~.~~ A number of heterocyclic compounds which have two phenyl groups on adjacent carbon atoms exhibit the ion C13H9' in their spectra.It is considered that formation of a C-C bond between the two benzene rings takes place prior to fragmentation in a manner analogous to (2).48In cyclic ~ulphones~~ the migration of a group from sulphur to oxygen takes place as was found with simple diary1 s~lphones.~' Other unusual rearrangements include the loss of hydrogen followed by nitrous oxide from dibenzylnitros- amine5' and the elimination of carbon dioxide from the molecular ion of (27).52 The structure of the ion produced by loss of carbon monoxide from 2-pyrone is still in doubt but it appears certain that those C4H40+' ions which have enough energy to decompose further do not have the furan structure.53 The molecular ions of enol acetates decompose by elimination of keten to produce ions of the same molecular weight as the parent ketones.54 Examination of further decompositions shows that they cannot have the same structure and it is suggested that the enols are formed.The C4R4+*ion formed from the molecular ion of substituted tetraphenylcyclopentadienones(28) appears to have a distorted tetrahedral rather than square symmetry.55 In an exhaustive study of the mass spectra of methyl esters of long-chain monocarboxylic acids using both I3Cand 2Hlabelling Dinh-Nguyen has shown that ions ofthe general formula CH,OCO[CH,],+ are formed by two processes partly by direct fission of the C-C bonds but mostly by a skeletal rearrangement pro- c~ss.~~ In the spectra of methyl esters of dicarboxylic acids ions of the general formula CH,OCO[CH,]~ decompose by loss of keten probably through an intermediate such as (29).5' 45 J.0.Madsen S.-0. Lawesson J. H. Bowie and R. G. Cooks Chem. Comm. 1968,698. 46 T. H. Kinstle and J. G. Stam Chem. Comm. 1968 185. 47 S. E. Schappele R. D. Grigsby E. D. Mitchell D. W. Miller and G. R. Waller,J. Amer. Chem. Soc. 1968,90 3521. 48 J. H. Bowie P. F. Donaghue H. J. Rodda and B. K. Simons Tetrahedron 1968,3965. 49 D. S. Weinberg C. Stafford and M. W. Scoggins Tetrahedron 1968,24 5409.50 S. Meyerson H. Drews and E. K. Fields Analyt. Chern.. 1964,36 1294. 51 T. Axenrod and G. W. A. Milne Chem. Comm. 1968,67. 52 J. Dekker and D. P. Venter J. Amer. Chem. Soc. 1968,90 1225. 53 W. H. Pirkle and M. Dines J. Amer. Chem. Soc. 1968 90,2318. 54 D. G. B. Boocock and E. S. Waight J. Chem. Soc (B) 1968,258. 55 M. M. Bursey D. Rieke T. A. Elwood and L. R. Dusold J. Amer. Chem. Soc. 1968,90 1557. 56 N. Dinh-Nguyen Arkzv Kemi 1968,28,289. 57 I. Howe and D. H. Williams J. Chem. SOC.(C) 1968,202. Mass Spectrometry 15 Ion intensities are difficult to correlate with structure in monoterpene mass spectra and a study of metastable ions in this series also suggests that such compounds may often decompose uia common intermediate^.^ * Theoretical calculations on C3H + ions indicate that the edge-protonated cyclopropane ion is stable with respect to C,HZ' + Applications of Various Techniques.-The problem of the determination of molecular formulae of compounds which have unstable molecular ions has been attacked by the use of three different techniques.The metastable-ion focussing technique has been used with some success.6o It has been possible to detect the transition CCl," + CCL; but in some cases it proved impossible to detect transitions of very unstable molecular ions. Negative-ion spectra have also been used. A report on such spectra for some sulphur compounds shows that some of these have stable negative molecular ions but those with acidic functions tend to have only the [M -HI -ion.61 The compound (30)is repor- ted to have a stable negative molecular ion.62 It has been shown that in the Me Me C.a:]' Me Me (31) (30) H-2u-H Me Me (33) (3 4) presence of a moderate pressure of a non-reacting gas e.g nitrogen there will be an increase in the flux of low-energy secondary electrons in the ion source which will increase the probability of electron attachment processes.63 The most successful method for dealing with the above problem has been field-ion mass spe~trometry.~~ Good spectra have been obtained for terpene~,~ but the most impressive results are the spectra of a series of unstable compounds all of which exhibited molecular ions the most spectacular being pentaery- thritol tetranitrate.66 Improvements in field-ionisation techniques have made H.C. Hill R. I. Reed and M. T. Robert-Lopes J. Chem. SOC. (C) 1968,93. 59 J. D. Petke and J. L. Whitten J. Amer. Chem. SOC.,1968 90 3338. 6o L. A. Shadoff Analyt. Chem. 1967,39 1902. 61 R. Mayer P. Rosmus M. von Ardenne K. Steinfelder and R. Tummler Z. Naturforsch. 1967 22B,1291. 62 R. S. Gohlke J. Amer. Chem. SOC. 1968 90 2713. 63 R. C. Dougherty and C. R. Weisenberger J. Amer. Chem. SOC. 1968,90 6570. 64 H. D. Beckey Internat. J. Mass Spectrometry Ion Phys. 1968 1 93. " H. D. Beckey and H. Hey Org. Mass Spectrometry 1968 1,49. 66 C. Brunee G. Kappus and K.-H. Maurer Z. Analyt. Chem. 1967,232 17. 16 John M. Wilson it possible to obtain high-resolution measurements on unstable ions,67 and to obtain sensitivities sufficiently reproducible for paraffin wax analysix6 Field-induced fragmentation is producing surprising results.The fragment ions produced from but-1-ene and but-2-ene are quite different.69 The technique of analysing the 14C content of fragment ions by measuring the radioactivity of photographic plates from a mass photograph7' has been applied to the problem of the fragmentation of salicyclic acid.7 The ion (3 1) decomposes by elimination of carbon monoxide from C-2 and not from the original carbonyl group. The structure of the product ion may be (32). A tech-nique for obtaining pure metastable mass spectra has been described in which kinetic-energy selection takes place between the magnetic analyser and the collector.72 By using such a system it has been possible to detect differences between the spectra of cis-and trans-but-2-ene.Williams has noted that since molecules containing functional groups with low ionisation potentials e.g. p-or rn-anisyl often show abundant molecular ions it should be possible to use such groups in the preparation of suitable derivatives for the determination of molecular weight^.^ Although in the interpretation of the spectra of saturated hydrocarbons the intensity of even- electron alkyl ions is usually considered it has been shown that odd-electron CnH2"+' ions are useful in the analysis of the spectra of multiply branched hydrocarbon^.'^ Although many examples of stereochemical effects on mass spectra have been reported the first case has been recorded of a difference in spectra between two compounds in which the stereochemical difference is due to the presence of deuterium atoms.The ratio [M-2HC1] [M -HCl] + [M -2HCl] is significantly greater for (33) than (34).75The mass spectra of cis-and trans-cyclic sulphites and carbonates are different at high temperatures but are quite similar at low temperatures. In these cases the pyrolytic processes are affected by stereochemistry but not the electron impact-induced decomposition^.^^ 67 E. M. Chait T. W. Shannon J. W. Amy and F. W. McLafferty Analyt. Chem. 1968,40 743. 68 W. L. Mead Analyt. Chem. 1968,40 743. 69 M. J. Weiss and D. A. Hutchinson J. Chern. Phys. 1968,48,4386. 70 H. Knoppel and W. Beyrich Tetrahedron Letters 1967 291. 71 J.L. Occolowitz Chem. Comm. 1968 1226. '' N. R. Daly A. McCormick and R. E. Powell Org. Mass. Spec. 1968 1 167. 73 A. N. H. Yeo and D. H. Williams J. Chem. SOC.,1968,2660. l4 E. D. McCarthy J. Han and M. Calvin Analyt. Chem. 1968 40,1475. l5 M. M. Green J. Amer. Chem. SOC.,1968,90 3872. 76 P. Brown and C. Djerassi. Tetrahedron. 1968,24,2949.

ISSN:0069-3030    

DOI:10.1039/OC9686500007

出版商:RSC    

年代:1968

数据来源: RSC

摘要:

2 (Part ii) ELECTRON SPIN RESONANCE SPECTROSCOPY By Colin Thomson (Department of Chemistry The University,St. Andrews Fife Scotland) THEuse of electron spin resonance spectroscopy (e.s.r.) in chemistry con- tinues to increase and two important books summarise the present state of this subject. The book by Ayscough provides an extensive survey of the chemical aspects of e.s.r.,’ whilst in ‘Radical Ions’,’ a series of authors review in detail electron spin densities ion-pair equilibria semidione anions aromatic anions and cations ions containing sulphur and Group IV elements orbital de- generacy inorganic radicals complex ions and various aspects of radical ions in radiation chemistry. This book is of immense value to the researcher in e.s.r. This report makes no attempt to cover all aspects of e.s.r.and the references cited are those which seem to the reporter to be of particular significance. Among reviews of interest are the use of 170in e.~.r.,~ a series of reviews in a Discussion of the Royal S~ciety,~ the use of e.s.r. in kinetic^,^ e.s.r. of the triplet state,6 and some more general reviews of e.~.r.~-’ The present report does not deal in detail with irradiated solids polymer e.s.r. gas-phase e.s.r. nor biological applications but concentrates on e.s.r. studies of radicals in solution and their relationship to valence theory. General Theory Hyperfiie Interactions and Spin Density Calculations.- The relationship between the observed hyperfine splitting (h.f.s.) constants a and the spin density distribution in the radical continues to be of interest.For n-electron radicals the McConnell relation :lo between proton splittings (aH)and the spin density (pc) on the contiguous carbon atom or the Karplus-Fraenkel” relationship (for 3C,1’N etc.) have continued to be used. However two recent papers have examined the approxi- mations involved in the McConnell derivation. Malrieu” has extended the P. B. Ayscough ‘Electron Spin Resonance in Chemistry,’ Methuen London 1967. E. T. Kaiser and L. Kevan ‘Radical Ions,’ Interscience New York 1968. B. L. Silver and Z. Luz Quart. Rev. 1967,21,458. Proc. Roy. SOC.,1968 A 302,287-365. Ya.S. Lebedev. UsprXhi. Khini.. 1968,37 934. C. Thomson Quart. Rev. 1968. 1968 22,45 ’ D. H. Eargie jun. Analyt. Chem.1968,40 303R. * G. A. Russell Science 1968,161 423. F. Gerson Chimia (Switz) 1968,22 293. lo H. M. McConnell J. Chem. Phys. 1956,24 764. M. Karplus and G. K. Fraenkel J. Chem. Phys. 1961,35 1312. l2 J.-P. Malrieu J. Chem. Phys. 1967. 46. 1654. 18 Colin Thomson original first-order perturbation theory treatment to second-order. The addi- tional contributions are at least 25% of the first-order and this is of the same order of magnitude as the corrections proposed by Colpa and B01ton.l~ A very detailed study by Davidson and co-~orkers'~ on the C-H fragment is similar to that of Malrieu but numerical calculations were carried out for various basis sets. The authors conclude that Q" depends on both first- and second-order effects and is very sensitive to the orbital exponent of the H atomic orbital.Calculated values of QF. lie in the range -25 < Q,!& < -50 G. These authors conclude that Bolton's13 calculation may be in error. Murrell and Hinchliffe' have calculated fluorine coupling constants uF by use of the Karplus-Fraenkel' ' approach and find reasonable correlations between observed and calculated uF for a series of fluoronitrobenzene anions if the n-electron spin densities are calculated by means of SCF-CI theory. Analysis of the results shows that uF is related to the Q factors by equation 2 i.e. the splitting also depends on the overlap spin densities pCF(these are very small for hydrogen splittings). A similar calculation of QENand Q& has been carried out.l6 Spin polarization mechanisms in aliphatic fragments have been investigated by Luz" using the Dirac vector model. Vincow18 has examined the use of the Colpa-Boltonl and Giacometti Nordio Pavan' relationships in deriving an expression for the total splittings in the cyclic ions C,H,* and the radicals C,HA. An unsatisfactory feature of correlations between h.f.s. and n-electron spin densities has been the semi-empirical nature of the Q factors in view of the difficulty of accurate calculations. The influence of a-electrons has recently been taken explicitly into account in all valence electron calculations which although semi-empirical should provide a more realistic picture of the spin distribution particularly in radicals containing heteroatoms.The extended Huckel Theory2' (EHT) has been used by Drago and Petersen2 in calculations on a-radicals such as vinyl cyclopropyl etc. The calculated coupling constants are in excellent agreement with experiment. A later paper22 has considered nitrogen and proton splittings in the o-radicals Hc0,H2cN and those derived from syn-and anti-acetaldoxime benzaldoxime and 2-pyridyl. For this type of radical EHT is a considerable improvement over Hiickel theory and it has also been applied to long-range couplings in ~emidiones.~~ A related but more l3 J. P. Colpa and J. R. Bolton Mol. Phys. 1963,6 273. l4 S. Y. Chang E. R. Davidson and G. Vincow J. Chem. Phys. 1968,49,529. A. Hinchcliffe and J. N. Murrell Mol. Phys. 1968 14 147. J. C. M. Henning Chem.Phys. Letters 1968 1 678. l7 Z. Luz J. Chem. Phys. 1968,48,4186. G. Vincow J. Chem. Phys. 1967,47,2714. l9 G. Giacometti P. L. Nordio and M. V. Pavan Theor. Chzm. Acta. 1963,l. 404. 'O R. Hoffman J. Chem. Phys. 1963,39 1397. " R. S. Drago and H. Petersen jun. J. Amer. Chem. SOC. 1967,89 3978 5774. 22 R. E. Cramer and R. S. Drago J. Amer. Chem. SOC.,1968,90,4790. 23 G. R. Underwood and R. S. Givens J. Amer. Chem. SOC.,1968,90,3713. Electron Spin Resonance Spectroscopy 19 rigorous theory based on the SCF formalism is Pople’s CND0/2 25 which has been applied to fluoronitrobenzene anions26 but it is also better suited to o-radicals. This disadvantage of both EHT and CND0/2 is that they neglect the 0-n exchange integrals which are involved in the spin polarization mecha- nism in n-electron radicals i.e.in the Q factor. The most notable advance in 1968 has been the application of an extension of the CND0/2 method including such integrals (INDO meth~d),~’ to hyperfine splitting calculations. The split- ting constant is calculated directly and agreement with experiment is very good for N 0,C H and F splittings in a large variety of radicals.28 The observed differences in geometry between eH3 and eF3are accounted for by use of this method.29 Further work with this method should be of great interest. Of the numerous n-electron spin-density calculations which have been reported the use of the unrestricted Hartree-Fock (UHF) theory has in- creased and has been applied to thiophen pyrrole and furan anions,3o and to alkyl radical^.^' Since this method is based on a wavefunction which is not an eigenfunction of S2 most authors have projected out the unwanted spin components after minimisation (PUHF method).Harriman and Sando have. however reported the first n-electron calculations using the Spin Extended HF method (in which projection is carried out before energy minimisation) for allyl pentadienyl benzyl and the anions and cations of naphthalene anthracene and a~ulene.~~ Despite the greater complexity of the method the results appear to be intermediate between those given by the UHF and PUHF methods. Linewidths and Relaxation Theory.-The extensive work on linewidths by Freed and Fraenke133 has been continued by Freed,34 by means of a new method due to K~bo.~’ This method should be of use in studying rotational effects on the g-tensor.Sille~cu~~ has examined quadrupole relaxation which is believed to be important in iodine-substituted iminoxy radicals. He obtained good ON* I 24 J. A. Pople D. P. Santry and G. A. Segal J. Chem. Phys. 1965,43 S129 S136. 25 J. A. Pople and G. A. Segal J. Chem. Phys. 1966,44,3289. 26 D. W. Davies Mol. Phys. 1967 13,465. 27 J. A. Pople D. L. Beveridge and P. A. Dobosh J. Chem. Phys. 1967,47,2026. 28 J. A. Pople D. L. Beveridge and P. A. Dobosh J. Amer. Chem. SOC. 1968,90 4201. 29 D. L. Beveridge P. A. Dobosh and J. A. Pople J. Chem. Phys. 1968,48,4802. 30 N. K. Ray and P. T. Narasimhan Theor. Chim. Acta. 1968,11 156. 31 N. K. Ray and P. T.Narisimhan Chem. Phys. Letters 1968,2 101. 32 J. E. Harriman and K. M. Sando J. Chem. Phys. 1968,48,5138. 33 J. H. Freed and G. K. Fraenkel J. Chem. Phys. 1963,39 326. 34 J. H. Freed J. Chem. Phys. 1968,49 376. ” R. Kubo J. Phys. SOC.Japan 1962,17,1100. 36 H. Sillescu Mol. Phys. 1968 14 381. Colin Thomson agreement between the theoretical and experimental linewidths for the radical (1). Sillescu and Kivelson have studied relaxation theory by use of a classical model for The use of Monte Carlo methods for calculating lineshapes has been further e~plored.~' In experimental work on linewidths the 2,2'- dinitrobiphenyl anion (2)has been studied.39 This anion. produced by reduction with sodium in dimethoxyethane shows linewidth alternation in the spectrum.Different metal cations exchange at different rates between the nitro groups and give rise to linewidth effects which are dependent on the metal solvent and temperature. a;X=O b;X=S 2,2'-Dinitrobiphenyl ether (3a) and sulphide (3b) ions were also studied.40 In the first case the two rings are magnetically equivalent with respect to the protons but not with respect to nitrogen. This is the first case reported where the exchange rate is fast with respect to one coupling constant and slow with respect to the other. A technique for improving the resolution of hyperfine structure in solid-state spectra has been described which is based on Fourier transform technique^.^^ Hydrocarbon Radicals Anions and Cations.-Triphenylmethyl Ph3C has recently been studied by electron nuclear double resonance (ENDOR).42 The ring splitting constants obtained from this study are a, = -2.609 G.a = -1.143G,and up = -2.857 G and were assigned on the basis of McLachlan calculation^^^ and observed and calculated e.s.r. spectra. Several chlorine- and fluorine-substituted derivatives have also been ~tudied.~~9 44 The diphenyl- methyl radical Ph,eH45 has been reported during thermolysis of various compounds which give diphenylmethylene when the reaction is carried out in solvents with abstractable hydrogen. The value of uHfor the C-H fragment is 8.36 G which Vin~ow~~ concludes is much lower than expected on the basis of his work on the structurally similar xanthyls. Further confirmation of this work 37 H.Sillescu and D. Kivelson J. Chem. Phys. 1968,48 3493. 38 M. Saunders and C. S.Johnson jun. J. Chem. Phys. 1968,48,534. 39 J. Subramanian and P. T. Narasimhan J. Chem. Phys. 1968,48 3757. 40 R. K. Gupta and P. T. Narasimhan J. Chem. Phys. 1968,48,2453. 41 A. Hedberg and A. Ehrenberg. J. Chern. Phys.. 1968.48.4822. 42 A. H. Maki. R. D. Allendoerfer. J. C. Danner. and R. T. Keys J. Anw. Chem. SOC.. 1968. 90. 4225. 43 A. D. McLachlan Mol. Phys. 1960,3,233. 44 J. Sinclair and D. Kivelson J. Amer. Chem. SOC. 1968,90 5074. 45 D. R. Dalton S. A. Liebman H. Waldman and R. S. Sheinson Tetrahedron Letters 1968,145. 46 M. D. Sevilla and G. Vincow J. Phys. Chem. 1968,72 3635. Electron Spin Resonance Spectroscopy is needed. Vincow has extended his earlier work on tropenyl radicals C7H7m4’ to the mono- and tri- t- butyltr~penyls.~~~~~ These substituents remove the degeneracy of the unpaired electron orbital and give spectra whose hyperfine splittings are very temperature-dependent.For the tri- t-butyltropenyl the linewidth and g-value are also temperature-dependent. A very detailed analysis is given of the vibronic near-degeneracy problem in these radicals. An interesting but unexplained spectrum is obtained by treating azulene with periodic acid.” The radical is very stable and analysis of the solid indicates that the azulene rings are present. Anion radicals derived from hydrocarbons con- tinue to be of interest. Smentowski’’ has succeeded in obtaining very well- resolved spectra by use of sodium in liquid ammonia as reducing agent.Care must be taken that reduction does not proceed to the dianion. Although C6H; could not be prepared several other hydrocarbon anions such as the anions of anthracene and naphthalene were stable at temperatures -= O”c and the benzophenone anion was stable up to +40°c. A detailed study of deuterium-substituted benzene anions has a~peared.’~ The degeneracy of the benzene molecular orbitals is lifted by deuterium substitution except where the radical has a three-fold or higher symmetry as in the case of [1,3,5-2H3]benzene. The temperature dependence of the split- tings was different from that observed in C6H; and the results were analysed in terms of perturbations of the benzene orbitals as a result of substitution.Radicals ions from several unusual hydrocarbons have been described. Monohomocyclo-octatetraene anion (4)has been re-inve~tigated’~ and the results show that the early work of Katz and TalcotP4 was correct but that the splitting constants of Winstein and co-workers” were in error. (4) (5) A very different spectrum is produced from the related species bicyclo[6,1,0]- nona-2,4,6-triene (3,which agrees with calculations based on structure (5).56 The azupyrene anion (dicyclopenta[ef,kl]heptalene anion) (6)has been observed and the splitting constants a = 0.64 G a3 = -4.23 G and a4 = 0.94 G are 47 G. Vincow M. L. Morrell W. V. Volland H. J. Dauben jun. and F. R. Hunter J. Amer. Chem. SOC.,1965,87 3527. 48 G. Vincow M. L. Morrell F. R.Hunter and H. J. Dauben jun. J. Chem. Phys. 1968,48,2876. 49 w. V. Volland and G. Vincow J. Chem. Phys. 1968,48,5589. 50 A. T. Fatiadi Chem. Comm. 1968,456. ” F. J. Smentowski and G. R. Stevenson J. Amer. Chem. SOC.,1968,90,4661. ’’ R. G. Lawler and G. K. Fraenkel J. Chem. Phys. 1968,49 1126. ” F. J. Smentowski R. M. Owens and B. D. Faubion J. Amer. Chem Soc. 1968,90 1537. s4 T. J. Katz and C. Talcott J. Amer. Chem. SOC. 1966,88,4732. 55 R. Rieke M. Ogliaruso R. McLung and S. Winstein J. Amer. Chem. SOC.,1966,88,4729. 56 G. Moshuk G. PetrowskYi and S. Winstein J. Amer. Chem. SOC.,1968,90,2179. Colin Thomson in good agreement with theoretical calculations.’ An interesting reaction occurs during the alkali-metal reduction of l,l’-binaphthyl(7).The binaphthyl 12 anion initially produced undergoes further reaction to give perylene anion (via the perylene dianion).’* The naphthacene trianion spectrum reported earlier,59 has been re-studied and shown to be due to the 5,12-naphthacene- semiquinone ion,60* 61 which emphasises the important of purity and the ex- clusion of oxygen from these systems. A large number of papers on ion-pair interactions have appeared including two very detailed studies of ion pairing in the naphthalene and anthracene anion-metal cation system^.^^-^^ These papers deal with the structure and stability of the ion-pairs. The various models differentiate between the strong and weak ion-pairs which are observed and the field as a whole has been reviewed by Sym~ns.~’ The pairing theorem for alternant hydrocarbons has been further studied by use of the biphenylene cation and anion66 (8).13C Splittings indicate that the theorem is valid in this case also as it was for anthracene ions,67 but there are large differences in Q“ at the 2-position in the cation and anion which are as yet unexplained. ” A. G. Anderson jun. A. A. MacDonald and A. F. Montana J. Amer. Chem. SOC. 1968 90 2994. S. P. Solodnikov S. T. Ioffe Yu. B. Zaks and M. I. Kabachnik Zzvest. Akad. Nauk S.S.S.R. Ser. khim 1968,442. 59 K. Mobius and M. Plato 2.Naturforsch 1964,199 1240. E. T. Seo J. M. Fritsch and R. F. Nelson J. Phys. Chem. 1968,72 1829. 61 K. Mobius and M. Plato J. Phys. Chem. 1968,72 1830. 62 N. Hirota J. Amer. Chem. SOC. 1968,90 3603.N. Hirota R. Carraway and W. Schook J. Amer. Chem. SOC.,1968,90 3611. 64 C. L. Dodson and A. H. Reddoch J. Chem. Phys. 1968,48,3226. 65 J. Burgess and M. C. R. Symons Quart. Rev. 1968,22,276. 66 P. R. Hindle J. dos Santos Veiga and J. R. Bolton J. Chem. Phys. 1968,48,4703. J. R. Bolton and G. K. Fraenkel J. Chem. Phys.. 1964,40. 3307. Electron Spin Resonance Spectroscopy 23 Cation dimers first observed for naphthalene by Lewis and Singer,68 have been produced from coronene and pyrene by use of the BF3-S02 oxidising 70 An excess of reagent gives the monomer but an excess of hydro- carbon gives the dimer. Other oxidising systems have also been reported to give the cation dimer of coronene such as BF3-CH2C12 S03-S02 AlC1,-MeN02.70 The hyperfine structure is well resolved and the splitting constant is temperature-dependent.There is also a species present in this system which may be the cation trimer.70 There have been several investigations of substituted hydrocarbons. An extensive study of alkoxy bezene anions has shown that vibronic mixing is small in these ions.7’ The metal splittings observed have been used to obtain in- formation on the structure of ion-pairs. The cation radicals of p-bis(methy1thio) benzene and p-bis(ethy1thio)benzene have been prepared by reaction with A1C1,-MeN02.72 The spectra were interpreted in terms of a superposition of spectra due to the cis-(9)and truns-(10) isomers with the splitting constants shown. /Me 5.30 G /Me 5.44G S S 0 1*03G \ 1.79 G S Me/s ‘Me (9) (10) McLachlan spin-density calculations support this assignment and different g-values are observed for the two species.72 The radical PhCOi- can be produced in a flow system by reaction of benzoic acid with sodium in liquid ammonia.73 The use of this technique for other systems should be interest.Radicals Containing Halogens.-The perfluoro-analogues of aliphatic and aromatic hydrocarbons have been prepared and extensively studied in recent and in view of the interest in the mechanism of fluorine hyperfine interactions the preparation of the anions and cations of perfluoro-species is of considerable interest. This year has seen the first studies of this type of radical. Although naphthalene does not give CloH; on oxidation only the dimer cation,68 perfluoronaphthalene CloFg can be oxidised to C,,F;.Bazhin et al. reported that this cation was formed in oleum SO3,or SbF,-(Me0)2S02 but their analysis of the spectrum was in error owing to the failure to observe I. C. Lewis and L. S. Singer J. Chem. Phys. 1965,43 2712. 69 J. T. Cooper and W. F. Forbes Canad. J. Chem. 1968,46,1158. 70 H. van Willigen E. de Boer J. T. Cooper and W. F. Forbes J. Chem Phys. 1968,49 1190. J. K. Brown and D. R. Burnham Mol. Phys. 1968,15 173. ’’ W. F. Forbes and P. D. Sullivan Canad. J. Chem. 1968,46,317. 73 A. R. Buick T. J. Kemp G. T. Neal and T. J. Stone Chem. Comm.. 1968. 1331. 74 R. E. Bank ‘Fluorocarbons and their derivatives,’ Oldbourne Press London 1964. Colin Thomson the outside lines.’ Independently Thomson and MacC~lloch~~ observed a strong 21-line spectrum by use of the new oxidising medium SbClS-SO2 with splitting constants uorF= 19.0 G ugF= 4-75 G i.e. uaF -4ugP The analysis of these spectra in terms of theory and of the pronounced linewidth effects which are observed should hopefully shed more light on fluorine hyperfine interactions. Several perfluoro-anions have been observed despite the tendency of such species to lose fluoride ion F-. The ketyls of (CF,),CO perfluorodimethyl keten and trifluoroacetophenone have been studied by Russian and (CF&CO independently by Jan~en.~~ Second-order splittings and y-fluorine h.f.s. are observed in hexafluorocyclobutanone.79The anions of several fluoro- and difluoro-benzophenones have been prepared electrolytically but decafluorobenzophenone does not give the simple anion.80 Correlations with Hiickel and McLachlan spin densities have been made for fluorine splittings in fluoro benzosemiquinones.However the above results all show that the relationship between uF and pc is not of the simple McConnell type aspredicted by Murrell and Hinchcliffe.” The anion radical from perfluorobenzoselenadiazole (11) and its H-analogue have been studied.82 In this case uF is twice a for the corresponding position in the benzoselenadiazole anion. The anion radicals of several difluoro- F 0. 0-II C Fi-N -N -C F3 biphenyls have been prepared by alkali-metal reduction. 83 Various fluoro- nitroaromatic radicals have been studied by Brown and Williams,84 who also reported that perfluoroaromatic hydrocarbons could not be reduced to the anion radicals because of loss of F-.Other workers have studied fluorine splittings from CF groups in several substituted nitro benzene^.^' An interest- ing reaction occurs during electrolysis of CF,NO and CF,N02.86The radical ” N.M. Bazhin N. E. Akhmetova L. V. Orlova V. D. Shteingarts L. N. Shchegoleva and G. G. Yakobson Tetrahedron Letters 1968 4449. l6 C. Thomson and W. J. MacCulloch Tetrahedron Letters 1968 5899. l7 V. V. Bukhtiyarov and N. N. Bubnov Teor. i. eksp. Khim. 1968,4,413. l8 E. G. Janzen and J. L. Gerlock J. Phys. Chem. 1967,71,4577. 79 J. L. Gerlock J. Phys. Chem. 1968,72 1832. 8o P. H. H. Fischer and H. Zimmerman Z.Naturforsch 1968,239 1339. 81 P. H. H. Fischer and H. Zimmerman 2.Naturforsch 1968,239 1399. 82 J. Fajer B. H. J. Bielski and R. H. Felton J. Phys. Chem. 1968 72 1281. 83 A. L. Allred and L. W. Bush Tetrahedron 1968,24,6883. 84 J. K. Brown and W. G. Williams Trans. Faruday SOC. 1968,64,298. ” J. W. Rogers and W. H. Watson J. Phys. Chem. 1968,72 68. 86 J. L. Gerlock and E. G. Janzen. J. Amer. Chem. SOC..1968.90. 1652. Electron Spin Resonance Spectroscopy produced is the bis(trifluoromethy1)semidiazoxide (12).Of considerable interest is the report that Cl,’ is produced on dissolving ClF in SbF or in Olah’s ‘magic acid’ FS03H-SbF,-S02. A seven-line spectrum characteristic of two equivalent I = 3/2 nuclei is observed with a = 2.5 G. The reaction mechanism is not clear but Cll is in equilibrium with another paramagnetic species (with may be ClF;) at higher temperature.This is the first observation of a diatomic radical cation in solution.87 Radicals Containing S Se Si Ge Sn and P.-Among recent Lvork on ring compounds containing S and Se we have mentioned perfluorobenzoselena- diazole82. In an attempt to assess the dependence of sulphur x-bonding on molecular geometry the non-planar molecule dibenzo[b,f]thiepin (13) was reduced to the anion by potassium in dimethoxyethane.88 The spin distribution is similar to that in the stilbene anion8’ and the authors conclude that conjugation through S is weaker than conjugation through the vinyl residue. The natural abundance of 33S(0.74%) is low but 33Sh.f.s.can be observed in some systems if the linewidths are small. The A1C13-MeN02 oxidising system has been used to study the 33S splittings (as)in the thianthrene (14) cation.g0 Linewidth studies show that the sign of a is positive. Sullivan has extended his studies to 33S splitting in several cations of thiepin (15) 1,4-benzothiepin (16) and phenoxathiin (17).9’ The theory of the 33Ssplittings is similar to the Karplus-Fraenkel theory of 3C splittings. Shineg2 has studied the oxidation of aromatic sulphides with persulphuric acid. Radicals are ob- tained whose g-values indicate that they are not the simple cation radicals but may be hydroxylated molecules. The trithienyl radicals (18) and (19) have been prepared and their solution e.s.r.spectra recorded although not completely analy~ed.’~ ’’ G. A. Olah and M. B. Comisarow,J. Amer. Chem. SOC.,1968,90 5033 88 M. M. Urberg and E. T. Kaiser J. Amer. Chem. SOC.,1967,89 5931. 89 C. S. Johnson,jun. and R. Chang,J. Chem. Phys. 1964,41,3272. H. J. Shine and P. D. Sullivan,J. Phys. Chem. 1968,72 1390. 91 P. D. Sullivan,J. Amer. Chem. SOC.,1968,90 3618. 92 H. J. Shine M. Rahman H. Nicholson and K.K. Gupta Tetrahedron Letters 1968,5255. 93 A. Mangini. G. F. Pedulli. and M. Tiecco. Tetrahedron Letters. 1968 4941. Colin Thomson R2 I An interesting recent observation of a small radica in solution is tile electro-lytic generation of In radicals containing Group IV elements several Ph,Si- substituted polyenes benzenes and naphthalenes have been prepared.95 Many of these are very stable and 29Si hyperfine structure (4.7% natural abundance) can be observed. The results provide some evidence for carbon n-orbital to silicon delocalisation. An independent study of Ph,Si- and Ph,Ge-substituted anions has appeared.96 Dimroth has extended his earlier work on cation radicals derived from 2,4,6-trisubstituted phosphor in^^^ with the preparation of 1,l-dialkoxy- and 1,l-diaryloxy-phosphorincations and anions (20).98An impor- tant recent report of the observations of PC12 and PCl radicals in u.v.-irradiated PC1 and MePC1299 at 77°K. has appeared. These small radicals should be of interest to theoreticians concerned with phosphorus hyperfine splittings. In a similar study U.V. irradiated triethyl phosphite at 77"~ gives (EtO),PO radicals.loo Radicals Containing Nitrogen.-(a) a-radicals.The carbamoyl radical (2 1) has been produced by reaction of H*CO*NH with OH in a flow system.''' These authors differ in their conclusions from earlier work,lo2 in which the radical was believed to be H-CONH and support their assignment with EHT calculations which give very good agreement with experiment. 94 K. P. Dinse and K. Mobius Z. Naturforsch. 1968,239,695. 95 F. Gerson J. Heinzer H. Bock H. Alt and H. Seidl Helv. Chim. Acta. 1968 51 707. 96 A. L. Allred and L. W. Bush J. Amer. Chem. SOC.,1968,90,3352. 97 K. Dimroth N. Grief W. Stade and F. W. Steuber Angew. Chem. Internat. Edn. 1967,7 711. 98 K. Dimroth and W. Stade Angew. Chem. Internat. Edn.1968,7 881. 99 G. F. Kokoszka and F. E. Brinkman Chem. Comm. 1968,349. loo K. Terauchi and H. Sakurai LW.Chem. SOC.Japan 1968,41 1736. T. Yonezawa I. Noda and T. Kawamura &ll. Chem. SOC. Japan 1968,41,766. lo' P. Smith and P. B. Wood Canad. J. Chem. 1966,41 3085. Electron Spin Resonance Spectroscopy 27 Electrochemical oxidation of nitrosobenzene and its derivative^"^ gives the radical cations (22) which are o-radicals since the splitting constants shown are typical of such species i.e. a large nitrogen coupling (aN= 37.0 G) and one large proton coupling (rneta) and other smaller proton splittings due to inter- action with one or three protons. Iminoxy radicals derived from halogen-substi- tuted acetophenones exhibit halogen splittings which are very dependent on temperature and solvent.'04 1,3-Dicarbonyl compounds react with C(NO,) to give various iminoxy radicals.' O5 (b) Nitrogen heterocyclic ions.The use of Pb(OAc) as an oxidising agent has been studied in the production of cation radicals of carbazole derivatives.'06 In the presence of acids as catalysts N-methyl- N-isopropyl- and N-phenyl- carbazole give stable radicals believed to be (23) although the spectra were not resolved. L R R J (23) (24) The behaviour of acridine (24) during reduction with sodium in tetrahydro- furan is complex but a thorough study of the species involved has detected the acridine anion which had not been reported previously. '07 Reaction of formazans (RN=NCR=NNHR) with tetrazolium salts (25) results in stable tetrazolinyl radicals (25a).'08 logA variety of derivatives were (25 ) (25d studied and McLachlan spin-density calculations were carried out.The results are consistent only with the cyclic structure (25a). Several new stable nitroxides have been reported e.g. (26),'" and the a-nitronylnitroxides (27)." '* 'l2 These radicals can be readily protonated with lo3 G. Cauquis M. Gemies H. Lemaire A. Rassat and J. P. Ravet J. Chem. Phys. 1967,47,4642. '04 B. C. Gilbert and R. 0.C. Norman J. Chem. SOC.(B),1968 123. lo' C. Lagercrantz and K. Torssell Arkiv. Kemi 1968 29,203. lo6 D. H. Iles and A. Ledwith Chem. Comm. 1968,498. lo' S. Niizuma M. Okuda and M. Koizumi hll. Chem. SOC.Japan 1968,41,795. F. A. Neugebauer Tetrahedron Letters 1968,2129.F. A. Neugebauer and G. A Russell J. Org. Chem. 1968,33,2744. L. B. Volodarsky G. A. Kutikova R. Z. Sagdeev and Yu. N. Molin Tetrahedron Letters 1968 1065. J. H. Osiecki and E. F. Ullman J. Amer. Chem. SOC. 1968 90,1078. 'I2 D. G. B. Boocock R. Davey and E. F. Ullman J. Amer. Chem. SOC. 1968,90 5945. Colin Thomson 0-+I I :0>: -b-0 CF,CO,H in benzene. Nitroxides (28) from binitrones have been described,' and a large number of azomethin nitroxides (29).l l4 A series of papers by Hudson and Hussain have examined the use of hydrogen peroxide to oxidise amines to nitroxides.' '-'l8 Very stable aliphatic nitroxides such as Me,NO can be produced and a large number of nitroxides derived from aliphatic amines cyclic amines etc.have been studied. In the latter case for instance with pyrrolidine nitroxide (30),interesting linewidth effects and strong temperature dependence of the spectra yield details of the conformation of the radicals. 2-Monosubstituted 1.3-dicarbonyl compounds react with I 0' C(NO,) to give nitroxides but the unsubstituted compounds give iminoxy radicals. Photolysis of alkyl nitrites in hydrocarbon solvents gives dialkyl nitroxides and alkoxy-alkyl nitroxides.' 2o However several interesting reactions occur in these systems by use of different solvents.'21 '13 A. R. Forrester R. H. Thomson and G. R. Luckhurst J. Chem. SOC.(B),1968 1311. '14 H. G. Aurich and F. Baer Chem. Eer. 1968,101 1770. A. Hudson and H. A. Hussain J. Chem. SOC.(B),1967 1299.A. Hudson and H. A. Hussain J. Chem. SOC.(B),1968 351. A. Hudson and H. A. Hussain J. Chem. SOC.(B),1968,953. '18 A. Hudson and H. A. Hussain J. Chem. SOC. (B),1968,1346. 'I9 C. Lagercrantz and K. Torssell Acta. Chem. Scand. 1968,22 1935. 120 A. Mackor Th. A. J. W. Wajer and Th. J. de Boer Tetrahedron 1968,24 1623. 12' S. Shih. R. J. Pritchett. and J. M. Rivero. Tetrahedron Letters. 1968. 4897. Electron Spin Resonance Spectroscopy (c) Nitro-and NH,-substituted radicals. Interest in nitroanions has centred on the study of ion-pair interactions particularly in 0-,rn- and p-dinitrobenzene anions reduced with alkali metals in a variety of solvents.'22* 123 The dependence of uN on counter ions temperature and solvent yields interesting information on solvent effects and ion-pair equilibria.Other systems of this type which exhibit interesting linewidth effects are 3,5dinitrobenzoate anions' 24 and s-trinitroben~ene.'~~ Fessenden has extended his in situ irradiation technique'26 with 2-8 Mev electrons (previously applied to alkanes and fluoroalkanes) to the study of nitroalkanes.' 27 Nitroalkane anions are produced and their spectra were interpreted. Tertiary nitroaliphatics can be reduced electrolytically to their anions' 28 which further react to give dialkyl nitroxides. An investigation into the photolysis of various substituted nitrobenzenes in tetrahydrofuran has shown that Ward's',' original interpretation of the radical as Phfi0,H is probably in~orrect.'~' The radical is believed to be (31) an adduct of nitrobenzene and a solvent radical.6 R' I I R = alkyl or H Ph'-N-0-C-R I Ph' = substituted phenyl Solvent = R1R2HCOR3 (31) R2 Several nitrobenzenes enriched with "0 have been studied and the signs of' Qo and of the splitting constant are negati~e.'~' Most nitro-compounds will not give the cation radical ; an exception is N,N-dimethyl-p-nitroaniline where both anion and cation have been studied.'32 Aryldinitromethanes can be reduced to divalent radical anions,'33 as well as to the dinitromethane radical (32) which results from secondary reactions. NO* H-C' 'NO (32) "' R. F. Adams and N. M. Atherton Trans. Faraday Soc. 1968,64 7. J. Oakes and M. C. R. Symons Chem. Comm. 1968,294. 124 W. E. Griffiths C.J. W. Gutch G. F. Longster J. Myatt and P. F. Todd J. Chem. SOC.(B) 1968,795. 125 R. K. Gupta J. Subramanion N. K. Ray and P. T. Narasimhan Chem. Phys. Letters 1968,2 150. R. W. Fessenden and R. H. Schuler J. Chem. Phys. 1963,39,2147. 127 K. Eiben and R. W. Fessenden J. Phys. Chem. 1968,72 3387. 12' H. Say0 and M. Masui Tetrahedron 1968,24,5075. R. L. Ward J. Chem. Phys. 1963,38 2588. 130 D. J. Cowley and L. H. Sutcliffe Chem. Comm. 1968,201. 13' W. M. Gulick jun, W. E. Geiger jun. and D. H. Geske J. Amer. Chem SOC.,1968,90,4218. 13' R. F. Nelson and R. N. Adams J. Phys. Chem. 1968,72,740. 133 K. Torssell C. Lagercrantz and S. Wold Arkiv. Kemi 1968,29 219. Colin Thomson (d) Other nitrogen-containing radicals. Diphenylpicrylhydrazyl has been re-investigated at K band and the most probable coupling constants (deter- mined by computer simulation) indicate that both nitrogens are equivalent.' 34 A number of studies of the oxidation of aniline have appeared.In basic solution PhNO- is formed.' 35 Oxidation by copper(I1) acetate however gives a complex species.' 36 Different radicals are produced under acid and basic conditions when amino- acids react with TiCl,-H,O,. In basic solutions glycine gives NH,cHCO; but a different species is produced at pH 3 which was not positively identified.' 37 A thorough study has appeared of the different methods of preparing azo- type radical anions.' 38 Several stable free radicals derived from thermolysis of aliphatic diazo compounds have been reported.These are believed to be biradicals or biradical polymers resulting from secondary reactions of the initially formed carbene.' 39 Radicals Containing Oxygen.-A detailed study of a variety of xanthyl radicals (33)by Sevilla and Vincow' 4"-1 42 indicates weak conjugation through the oxygeq. H The 9-phenyl xanthyl is non-planar and 9-alkyl xanthyls exhibit considerable hindered rotation. These are structurally related to diphen~lmethyl.~~ Ketyl radical ions well known in solution have also been prepared in the solid state by use of the rotating cryostat method.'43 Linewidth effects in semi- quinone anion system^'^^'^^ have been studied by several authors and like the nitrobenzenes (refs. 122 and 123) have yielded interesting information on 134 Z.Haniotis and Hs. H. Gunthard Helv. Chim. Acta. 1968,51 561. 13' R.Konaka K. Kuruma and S. Terabe J. Amer. Chem. SOC.,1968,90,1801. 136 A. van Heuvelen and L. Goldstein J. Phys. Chem. 72,481. 137 R. Poupko B. L. Silver and A. Lowenstein Chem. Comm. 1968,453. 138 G. A. Russell R. Konaka E. T. Strom W. C. Danen K. Y. Chang and G. Kaupp J. Amer. Chem. SOC.,1968,90,4646. lJ9 L. S. Singer and I. C. Lewis J. Amer. Chern. SOC., 1968,90,4212. 140 M. D. Sevilla and G. Vincow. J. Phys. Chern.. 1968.72. 3635. 14' M. D. Sevilla and G. Vincow. J. Phys. Chem.. 1968 72. 3641. M. D. Sevilla and G. Vincow J. Phys. Chem. 1968,72,3647. 143 J. E. Bennett B. Mile and A. Thomas J. Chem. SOC.(A),1968,298. 144 P. S. Gill and T. E. Gough Trans. Faraday SOC.,1968,64 1997.145 P. S Gill and T. E. Gough Canad. J. Chem. 1968,46 656. 146 T. A. Claxton J. Oakes and M. C. R. Symons Trans. Faraday SOC. 1968,64 59. 14' T. A. Claxton and J. Oakes Trans. Faruday SOC. 1968,64 607. 148 J. Oakes and M. C. R. Symons Trans. Faraday SOC.,1968,64,2579. 149 D. H. Chen E. Warhurst and A. M. Wilde Trans. Faraday SOC.,1968,64,2561. A. W. Rutter and E. Warhurst Trans. Faraday SOC.,1968,64,2338. Electron Spin Resonance Spectroscopy the structure and properties of the ions and ion pairs. Activation energies for the two-site jumping process involving the cation have also been determined.' 5' The AlC13-MeN02 system has been used to prepare the cation radicals of several dimethylhydroquinones. These can exist in both cis and transforms.' 52 Russell has extended his detailed studies of the radical anions of diketones the semidiones.' Of particular interest is his study of 7Ohyperfine structure' 54 in which the results indicate an equation of the type ao = Q%o which describes the results quite well if Qg = -40 & 4 G.The parameter Q" has been determined from the spectrum of the semidione (34) and is (0.4) G.lS5 The value of this parameter has been in dispute for some time. (34) Radicals in Flow Systems.-The Ti3+-H202 system for generating 'OH' radicals continues to be widely used although the controversy over the nature of the oxidising radical is still not resolved. Florin et conclude from kinetic data that OH is not present but that the species involved is an ionized complex of Ti3+ with H6,.This interpretation differs from that of Takakura' 57 who concludes that 6H and OH are present both co-ordinated with Ti" The organic radicals produced are however usually well defined. Amino- acids undergo abstraction from C-H bonds distant from the -fiH3 group.'58 Ti3+ together with t-butylhydroperoxide gives eH3 which reacts with added organic and inorganic molecules.' A potentially useful reaction is the production of R6 radicals during photo- lysis of di-t-butylhydroperoxide in iso-octane containing alcohols.' 6o Alcohol radicals ReHOH are produced as in the usual experiments but this reaction can be carried out in non-polar organic solvents and should be readily extended to other molecules. Reaction of Ti3+-H202 with anisole and acetanilides does not result in the expected OH adducts although C,H,F does add OH like benzene and 15' J.C. Chippendale and E. Warhurst Trans. Faraday SOC..1968 64 2332. lS2 P. D. Sullivan and J. R. Bolton J. Amer. Chem. SOC. 1968,90 5366. Ref. 2 p. 87. G. A. Russell and G. R. Underwood J. Phys. Chem. 1968,72 1074. 15' G. A. Russell J. McDonnell and C. Myers J. Phys. Chem. 1968,72 1386. lS6 R. E. Florin F. Sicilio and L. A. Wall J. Phys. Chem. 1968,72 3154. 15' K. Takakura and B. Ranby J. Phys. Chem. 1968,72 164. H. Taniguchi,K. Fukui S. Ohnishi H. Hatano H. Hasegawa and T. Maruyama J. Phys. Chem. 1968,72 1926. D. Mickewich and J. Turkevich 1.Phys. Chem. 1968,72,2703. 160 J. Q. Adams J. Amer. Chem. SOC. 1968,90 5363. 32 Colin Thomson phenols.'61 An interesting reaction occurs during addition of Grignard reagent to quinobromides in that phenoxy radicals (35)are formed'62 i.e.RQR RMgX RQR R (35) Radicals Produced by Photolysis in Solution.-Several interesting photo- chemical studies have appeared. The n + n* triplet state of biacetyl has been used to test electrophilic and radical-like properties of the carbonyl n -+ n* states with benzenoid compounds.163 With benzene at pH 0-5,the protonated semidione is produced. Nitrobenzene gives the protonated derivative PhN0,H. In a similar study of benzophenone and ben~aldehyde'~~ H abstraction occurs and Ph2t0H and PheHOH are observed. No solvent radicals were detected. Zeldes and Livingston have continued their earlier work on liquids during photolysis and have examined the radicals from acid amides imide~,'~~ and aliphatic nitroanions.'66 Triplet States.-The study of organic triplet states in both glasses and single crystals continues to be of interest.The observed spectra give the parameters D and E which can be calculated from the electronic wavefunction. Several such calculations have appeared including zero field splitting in polyphenyl- benzenes,'67 and an extensive calculation on the C1,H triplet including accurate two- three- and four-centre integrals.'68 The results are not much better than for more approximate calculations and the desirability of all- electron calculations remains. In experimental work on triplet states several nitrogen heterocyclics biphenyl acenaphthene and tetramethylpyrazine have been ~tudied.'~' The latter is a n + n* state unlike the pyrazine triplet which is n -+ n*.Benzene has been investigated in a single crystal'70 and the non-trigonal symmetry was confirmed.Usually the low-field transition (Am= 2) do not show hyperfine structure. An exception is found with 1-and 2-fluoronaphthalene where aPrFcan be mea~ured.'~'The value is close to that reported for C,,F; in solution.76 16' C. R. E. Jefcoate and R. 0.C. Norman J. Chem. SOC.(B) 1968,48. 16' A. A. Volod'khin M. V. Tarkhanova A. L. Buchachenko and V. V. Ershov Izvest. Akad. Nauk S.S.S.R. Ser. khim 1968 57. 163 E. J. Baum and R. 0.C. Norman J. Chem. SOC.(4,1968,227. 164 R. Wilson J. Chem. SOC.(4,1968,84.R. Livingston and H. Zeldes J. Chem. Phys. 47,4173. 166 H. Zeldes and R. Livingston J. Amer. Chem. SOC.,1968,90,4540. M. K. Orloff and J. S. Brinen J. Chem. Phys. 1968,47,3999. 16* C.Thomson Theor. Chim. Acta. 1968 11 165. 16' Y. Gondo and A. H. Maki J. Phys. Chem. 1968,72,3215. 170 M. S. de Groot I. A. M. Hesselmann and J. H. van der Waals Mol. Phys. 1968 13 583. "' P. H. H. Fischer and K. H. Hawser Chem. Phys. Letters 1968,1 665. Electron Spin Resonance Spectroscopy 33 An interesting observation on the triplet dianions of 1,3,5-triphenylbenzene has been re~0rted.I~~ The spectra show that three triplet states are present and these are believed to be due to unperturbed dianion and to two new species in which successive solvation of the dianion by alkali-metal counter-ions occurs.The important technique of optical spin polarisation has been success- fully used in the study of the emissive e.s.r. lines from the naphthalene tri~1et.I~~ Miscellaneous.-Quintet states,' 74 quartet states,' 75 and even a septet state (in a nitrene) have been detected by e.~.r.'~~ Many papers have appeared dealing with radicals produced by high-energy radiation but two seem to be of particular importance. Pulse radiolysis techniques have been used to study radical formation and decay in systems where the radical half life is of the order of mse~.'~~ Using a similar technique Avery et al. have reported the e.s.r. spectrum of H30+ (lifetime ca. 10 msec.) in aqueous methan01.l~~ Radicals whose lifetime in solution is too short for them to be observed directly may be trapped and identified by reaction with nitroso-compounds' 79 or phenyl-t-butyl nitrone.180 Both these give stable nitroxides and from the spectrum the nature of the short-lived radical may be inferred.Finally two recent papers have described methods by which high-resolution e.s.r. spectra of radicals with lifetimes of ca. 1 msec. may be observed.18',182 "' J. A. M. van Brockhoven H. van Willigen and E. de Boer Mol. Phys. 1968,15 101. 173 M. Schwoerer and H. C. Wolf Chem. Phys. Letters 1968,2 14. 174 K. Itoh H. Konishi and N. Mataga J. Chem. Phys. 1968,48.4789. 17' E. Wasserman K. Schueller and W. A. Yager Chem. Phys. Letters 1968 2 259. 176 G. R. Luckhurst and E. R. Rozantsev Izvest.Akad. Nauk S.S.S.R. Ser. khim 1968 1708. 177 R. Hirasawa T. Mukaibo H. Hasegawa N. Odan and T. Maruyama J. Phys. Chem. 1968 72 2541. 17' E. C. Avery J. R. Remko and B. Smaller J. Chem. Phys. 1968,49,951. 179 C. Lagercrantz and S. Forschult Nature 1968,218 1247. E. G. Janzen and B. J. Blackburn J. Amer. Chem. Soc. 1968,90,5909. P. W. Atkins K. A. McLauchlan and A. F. Simpson Chem. Comm. 1968 179. lS2 P. W. Atkins K. A. McLauchlan and A. F. Simpson Nature 1968,219 927.

ISSN:0069-3030    

DOI:10.1039/OC9686500017

出版商:RSC    

年代:1968

数据来源: RSC

摘要:

2 Part (iii) OPTICAL ROTATORY DISPERSION AND CIRCULAR DICHROISM by P. M. Scopes ( Westfield College Hampstead London N.W.3.) THEchiroptical techniques,’ optical rotatory dispersion (0.r.d.) and circular dichroism (c.d.) are increasingly finding a place as routine tools in organic chemistry particularly for natural products from the smallest molecule to biopolymers. Applications of 0.r.d. and c.d. to stereochemical problems increased by more than 50% this year by comparison with 1967 and there was also a large increase in published work concerned primarily with the development of the two techniques ; three have been published and also a French edition of CrabbC’s valuable book? At present virtually all measurements of 0.r.d. and c.d. are made on liquid samples but advances have been made this year towards work in the gaseous and solid phases.The c.d. of ( +)-3-methylcyclopentanone vapour has been examined6 in the vacuum U.V. region down to 167 nm; three optically active absorption bands were noted below 200 nm as well as the usual carbonyl n -,x* transition at ca. 300 nm. In order to measure the c.d. of a crystalline solid the sample must be suspended in a disc of chemically inert optically transparent and non-iso- tropic medium. Kahn and Beychok’ have used a mull of a silicon polyether with hexagonal crystals of L-cystine to investigate the relationship between the solid phase c.d. and the chirality of the disulphide bond Ollis Mason and V. Paelog K. Ned. Akad. Von Wetenschappen 1968 B71 108 c$ also U.Wheis Experientia 1968 24 1088. G. Snatzke Angew. Chem. 1968,80 15. S. Beychok Ann. Rev. Biochem. 1968,37,437. J. A. Schellman Accounts Chem. Res. 1968 1 144. P. Crabbe ‘Applications de la Dispersion Rotatoire Optique et du Dichroisme Circulaire Optique en Chimie Organique,’ Gauthier-Villair Paris 1968. S. Feinleib and F. A. Bovey Chem. Comm. 1968,978. ’ P. C. Kahn and S. Beychok J. Amer. Chem. SOC.,1968,90,4168. P.M. Scopes their collaborators* have used a similar technique with KCl discs to establish the chirality (M)for the propeller conformation adopted by ( +)-tri-o-thymotide in the solid state (I).The molecule was shown to adopt the same conformation in ethereal solution at -78". in general the development of low temperature c.d.has been disappointingly slow hampered by the lack of suitable commercially-available jacketed cells. The potential use of this method for conformational studies is very great as illustrated this year by work on acyclic ketones (acylated steroid^)^ and on unsaturated steroid ketones." Practical methods and instrumentation have been reviewed by Gervais.' ' Symmetry Rules.-Curbonyl chrornophore. There has been considerable controversy in the past over theoretical treatments of the origin of Cotton effects and over the symmetry rules which relate the sign and magnitude of a Cotton effect to the geometry of the dissymmetric surroundings of a symmetrical chromophore (cf previous Ann. Reports). The present theoretical situation has been well reviewed by S~hellman,~ who stated that the three mechanisms which have been proposed to explain the origin of optical activity i.e.the one- electron mechanism the coupling of two electric transition moments and the coupling of one electric and one magnetic moment should be regarded as complementary and not as alternatives. In particular Schellman discusses the symmetry rules for the peptide and carbonyl groups and cites further evidenceI2 which supports an octant (as opposed to quadrant) rule for ketones. c$ also the important paper by Hohn and Weigang on electron correlation models which deals in great detail with the carbonyl group.I3 The octant rule has been further explored by Djera~si'~" and by Snatzke14' who have synthesised a series of conformationally rigid adamantanones with substituents in specific selected positions.Equatorial substituents a-to a carbonyl group in a cyclohexanone ring have been shown to make small but measurable contributions to the carbonyl Cotton effect.' P-Substituted adamantanones have been investigated in detailI4 and some substituents e.g. CO,H have been shown to be anti-octant in their behaviour when substituted axially but to follow the normal rule when substituted equatorially. Previous workers have reported a 'reverse octant rule' for the n -+ x* Cotton effect of a-cyclopropyl- and a-epoxy-ketones. A thorough c.d. investiga- tion of about twenty such ketonesf5 has shown that the sign of the n + 7c* * A. P. Downing W. D. Ollis 1. 0.Sutherland J. Mason and S.F. Mason Chem. Comm. 1968 329. G. Snatzke D. M. Piatak and E. Caspi Tetrahedron 1968,24,2899. lo G. Snatzke and K. Schaffner Helu. Chim. Acta 1968,51 986. H. P. Gervais Compt. rend. 1967,264 B 1192. l2 T. D. Bouman and A. Moscowitz J. Chem. Phys. 1968,48,3115 Cf also R. M. Lynden-Bell and V. R. Saunders J. Chem. SCC.(A),1967,2061. l3 E. G. Hohn and 0.E. Weigang J. Chem. Phys. 1968,48 1127. I4O W. S. Briggs M. Suchy and C. Djerassi Tetrahedron Letters 1968 1097. 14* G. Snatzke and G. Eckhardt Tetrahedon 1968,24 4543. l5 K. Kuriyama H. Tada Y. K. Sawa S. It8 and I. Itoh Tetrahedron Letters 1968 2539; cf W. Reusch and P. Mattison Tetrahedron 1968,24 4933; F. K. Butcher R. A. Coombs and M. T. Davies Tetrahedron 1968.24 4041. Optical Rotatory Dispersion and Circular Dichroism 37 Cotton effect is determined by the octant in which the -CH2-group (cyclo- propylketones) or -0-group (epoxyketones) lies; the sign follows the normal and reversed octant rules respectively; An important study of a$-unsaturated ketones has appeared16 and also detailed reports on the 0.r.dJc.d.of the limonoids’ and on steroid-3-ethylene-dithio-4-ketones;’ the absolute configuration of twistane has been assigned from an 0.r.d. study of related ket0nes.l’ Aromatic chromophores. An account has appeared2’ of the allotment of absolute configuration to twenty representative members of the tetracyclin group. N.m.r. was used to establish the relative configuration of the chiral centres within each compound and the absolute configuration was established by empirical comparison of the c.d.curves with those of daunomycin of known absolute stereochemistry.2 ’ The conformation of the tetracyclins in solution has also been studied by c.d.22 Much interest has been shown in fla~ans,~~.~~ isoflavans2’*26 and related compo~nds.~ Many detailed investigations among alkaloids include those in the yohim- bane28 and eburnane2’ series and of the keto-indo1e3O pr~toberberine~’ and ly~orine~~ types. Other work includes that on small conformationally-labile aromatic mole- cules and on large inherently dissymmetric helical compounds. 34 Sulphur and phosphorus chromophores. There has been a remarkable surge of interest in sulphur chromophores during the past year. The inherent chirality of the disulphide bond in L-cystine has been discussed l6 H.Ziffer and C. H. Robinson Tetrahedron 1968,24,5803. l7 D. L. Dreyer Tetrahedron 1968,24,3273. C. H. Robinson L. Milewich G. Snatzke W. Klyne and S.R. Wallis J. Chem SOC. (C) 1968 1245. l9 K. Adachi K. Naemura and M. Nakazaki Tetrahedron Letters 1968 5467. 2o H. Brockmann H. Brockmann Jun. and J. Niemeyer Tetrahedron Lezters 1968 4719 preliminary work H. Brockmann Jun. and M. Legrand Tetrahedron 1963 19 395. 21 F. Arcamone G. Cassinelli G. Franceschi P. Orezzi and R. Mondelli Tetrahedron Letters 1968 3353. 22 L. A. Mitscher A. C. Bonacci and T. D. Sokoloski Tetrahedron Letters 1968,5361. 23 W. Gafield and A. C. Waiss Chem. Comm. 1968,29. 24 K. R. Markham and T. J. Mabry Tetrahedron 1968,24 823.25 L. Verbit and J. W. Clark-Lewis Tetrahedron 1968 24 5519. K. Kurosawa W. D. Ollis B. T. Redman I. 0. Sutherland 0.R. Gottlieb and H. Magalhaes Alves Chem. Comm. 1968 1265. ” W. D. Ollis C. A. Rhodes and I. 0.Sutherland Tetrahedron 1967,23,4741. *’ J. Trojanek Z. Koblikova and K. Blaha Coll. Czech. Chem. Comm. 1968,33,2950. 29 K. Blaha K. Kakova Z. Koblikova and J. Trojanek Coll. Czech. Chem. Comm. 1968,33 3833. 30 W. Klyne R. J. Swan A. A. Gorman A. Guggisberg and H. Schmid Helv. Chim. Act4 1968 51. 1168. 31 T. Kametani and M. Ihara .I.Chm. SOC.(C) 1968 1305. K. Kotera Y. Hamada and R. Mitsui Tetrahedron 1968,24,2463. 33 H. E. Smith M. E. Warren and L. I. Katzin Tetrahedron 1968 24 1327; L. Verbit and P. J. Heffron Tetrahedron 1968,24 123 1 ; L.Verbit A. S. Rao and J. W. Clark-Lewis Tetrahedron 1968 24,5839. 34 R. H. Martin M. F. Barbieux J. P. Cosyn and M. Gelbcke Tetrahedron Letters 1968 3507; H. Wynberg and M. B. Groen J. Amer. Chem. SOC. 1968 90. 5339; H. Musso and W. Steckelberg Ber. 1968 1510. 38 P.M. scopes in an important paper by Coleman and Blo~t.~~ Computer analysis resolved the observed c.d. curve into three separate maxima including a very strong negative maximum at 187 nm. This band is attributed to the dissymmetry of the disulphide group and corresponds to the anomolously large rotations which have been observed previously at cu. 200 nm for cystine and proteins containing cystine (cf other work on di~ulphides~~). Papers have appeared on several types of compound where the asymmetry arises from different configurations at a hetero-atom.The empirical rule which relates the sign of the Cotton effect at cu. 200 nm to the absolute configuration at the sulphur atom in methy1a1ky1su1phoxides3’has been clarified by Mislow and his colleagues ;38 steroidal sulphoxides have also been explored in detail.39 An intriguing correlation the ‘inter-system matching of Cotton effects’ has been noted by Mislow4’ for the c.d. curves of three aryl sulphoxides and three closely related phosphine oxides. Each pair of compounds was known from external evidence to have the same absolute configuration and to differ I I only in the replacement of O=S by O=P-Me and by one methyl group at I I a remote position in one aromatic ring (11) and (111).The c.d. curves of the sulphoxides corresponded very closely in sign and shape to those of the phosphine oxides. This sort of agreement would normally be regarded as fortuitous but in this case seems to provide a dramatic confirmation of the independently-assigned absolute configurations. For other work on asym- metric phosphorus derivatives see ref. 41. A major difficulty of the chiroptical techniques is made evident in a study by Djerassi et of steroid thiocyanates having an optically active weak absorption band at ca. 250 nm. On the assumption that this transition for 35 D. L. Coleman and E. R. Blout J. Amer. Chem. SOC.,1968,90,2405. 36 M. Carmack and L. A Neubert J. Amer. Chem SOC.,1967,89,7134;A. F. Beecham J.W. Loder and G. B. Russell. Tetrahedron Letters 1968. 1785. 37 K. Mislow M. M. Green P. Law. J. T. Melillo. T. Simmons. and A. L. Ternay. J. Anier. Chem. SOC.,1965,87 1958. 38 M. Axelrod P. Bickart M. L. Goldstein M. M. Green A. Kjaer and K. Mislow Tetrahedron Letters 1968 3249. 39 D. N. Jones M. J. Green and R. D. Whitehouse Chem. Comm. 1968 1634; D. N. Jones D. Mundy and R. D. Whitehouse ibid. 1636; D. N. Jones. M. J. Green M. A. Saeed and R. D. White- house J. Chem. SOC.(C) 1968 1362. 40 F. D. Saeva D. R. Rayner and K. Mislow J. Amer. Chem. SOC.,1968,90,4176. 41 W. D. Balzer Tetrahedron Letters 1968 1189; C. Donninger and D. H. Hutson Tetrahedron Letters 1968,4871. 42 C. Djerassi D. A. Lightner D. A. Schooley K. Takeda T. Komeno and K.Kuriyama Tetra-hedron 1968,24,6913. Optical Rotatory Dispersion and Circular Dichroism 39 thiocyanates is qualitatively analogous to the n -+ n* transition of a~ides,~~ the authors suggest that an octant rule should be obeyed. In the absence of rigid -SCN derivatives this cannot be rigorously tested ;instead the observed c.d. and the proposed rule are used to suggest the preferred conformations of the thiocyanate group with respect to the steroid mucleus. This work serves to emphasise the need for detailed studies wherever possible on compounds of rigid geometry and also the fact that in our present state of knowledge the chiroptical techniques answer only one question at a time. Chromophoric derivatives. The azide octant has been used to study the preferred conformation around the C-N bond in azidosugars ;44 further work has also appeared on benzimidazole and quinoxaline derivatives of carbohydrate^.^^ Dimedone derivatives of amines have been investigated in and it has been shown that derivatives of aliphatic amines have the R or S configuration give positive or negative Cotton effects respectively at ca.280 nm. The solvent dependence of the c.d. for some N-thiobenzoylamino- acids and peptides has been examined.47 Carboxyl chromoyhores. There has been much interest in attempts to define a symmetry rule for the carboxyl chromophore (cJ:previous Ann. Reports); an apparent anomaly in the early treatment of the lactone Sector rule has now been discussed fully.48 Beecham has suggested that the fundamental factor determining the sign of a lactone Cotton effect is the chirality of the lactone ring itself and that more remote parts of the molecule make only negligible contributions to the r~tation.~’ The Cotton effects observed in some 7-ace- toxyrosenono lactone derivatives are so strong as to suggest interaction between the lactone and acetate chromoph~res.~~ Detailed studies have been made on several quite distinct groups of carboxylic acids and esters including diterpene acids,51 and an homologous series of steroid-17~-carboxylicesters.52 A comparative study of the u.v./o.r.d./c.d.behaviour of many common hydroxy- and amino-acids has been made by Katzin and GulyasS3 over a wide pH range ; three studies of arylamino-acids have been made.54 The interest in amino-acids is typical of the general attention being given to those small molecules which are the building blocks for biologically im- portant macromolecules.It is outside the scope of this review to discuss in 43 C Djerassi. A. Moscowitz. K. Ponsold and G. Steiner. J. Anier. Cheni. Sac.. 1967. 89. 347. 44 H. Paulson. Chrni. &r. 1Y6X. 101. 1571. 45 W.S. Chilton and R. C. Krahn J. Aniei-. Chetn. Soc. 1968 90,1318. ’’ P. Crabbe B. Halpern and E. Santos Tetrahedron 1968 24 4299. 4315. 47 G. C. Barrett Chem. Comm. 1968 40. 48 W. Klyne. P. M. Scopes. R. C. Sheppard. and S. Turner. J. Chem. SOC.(C) 1968 1954. 4’) A. F. Beecham. Trtrtrlirdr-or1 Lcrtrr-.j. 196X. 2355. 35Y 1. 5o C. W. Holzapfel and P. S. Steyn. Tetrrrhrrlron.196X. 24,3321. J. D. Renwick and P. M. Scopes J. Chem SOC.(C) 1968,1949. 52 J. D. Renwick and P. M. Scopes J. Chem. SOC.(C) 1968,2574. 53 L.I. Katzin and E. Gulyas J. Amer. Chem. SOC.,1968,90 241. 54 1. Frif. V. Spiro and K. Blaha. Coll. Czech. Chem. Comm.. 1968,33. 4008 cf also H. Wyler and J. Chiovini. Hek. Chini. Acru. 1Y68. 51 1476 and Y. P. Myer and L. H. MacDonald. J. .Amer. Cheni. Soc... 1967 89 7142. P.M. Scopes detail the 0.r.dJc.d. of macromolecules but significant work has appeared on monosaccharide^,^^ small pep tide^,'^ and mononucleosides.57 A fascinating paper by Gabbay” describes the c.d. induced in an optically inactive aromatic amine added to RNA or to DNA. The ‘reporter’ molecule exhibits a positive maximum near 360 nm when added to RNA and a negative maximum when added to DNA.These results may be compared with the 0.r.d. and c.d. associated with charge-transfer bands and observed for intra- and inter-molecular electron-donor-acceptor complexes of amino-acids and peptides,” and suggest a potential method for studying helix topography. Magnetic Optical Rotatory Dispersion and Magnetic Circular Dichroism (m.0.r.d. and m.c.d.).-Recently a number of important papers have appeared on m.0.r.dJm.c.d. (chiefly the latter) and it is hoped that this subject may be reviewed in Ann. Reports in the near future. These techniques are not dependent on the presence of a chiral structure and their applications in structural chemistry are mainly concerned with studying the nature of the electronic transitions corresponding to a particular absorption.As spectroscopic tech- niques m.0.r.dJm.c.d. are particularly sensitive but almost inevitably equipment will be of great expense. A review of this work has appeared,60 and the variety of compounds which may be studied by the technique is illustrated by papers on chlorins,6 lU annulenes,61b and nucleosides,61C on aliphatiP2 and on aromatic hydrocarbon^.^^ 55 I. Listowsky G. Avigad and S. Englard Carbohydrate Rex 1968 8 205; I. Listowsky and S. Englard Biochem. Biophys. Res. Corn. 1968,30 329. ” D. R. Dunstan and P. M. Scopes J. Chem SOC. (C) 1968 1585. ’’ D. W. Miles S. J. Hahn R. K. Robins M. J. Robins and H. Eyring J. Phvs. Chem.. 1968 72 1483 and preceding papers. 58 E. J.Gabbay J. Amer. Chem SOC. 1968,90 6574. 59 P. Moser Helu. Chim. Act4 1968,51 1831. ‘O B. Briat and C. Djerassi Nature 1968,217 918. 61 B. Briat D. A. Schooley R. Records E. Bunnenberg and C. Djerassi J. Amer. Chem. SOC. 1967 89 (a) 6170; (b) 7062; (c) W. Voelter R. Records E. Bunnenberg and C. Djerassi ibid. 1968 90 6163. 62 H. K. Wipf J. T. Clerc and W. Simon Helu. Chim. Acta 1968,51 1051 1162. 63 P. J. Stephens P. N. Schatz A. B. Ritchie and A. J. McCaffery J. Chem. Phys. 1968,48 132.

ISSN:0069-3030    

DOI:10.1039/OC9686500035

出版商:RSC    

年代:1968

数据来源: RSC

摘要:

2 Part (iv) X-RAY CRYSTALLOGRAPHY By George Ferguson (Department of Chemistry The University of Glasgow Glasgow W.2 Scotland) OF the new text books which reflect the growing interest of organic chemists in crystal structure determination that of G. H. Stout and L. H. Jensen’ is noteworthy for its clear and detailed description of organic crystal structure determination. A new monograph by L. V. Azaroff2 also deals thoroughly with the theory and practice ofcrystal structure determination and in its later chapters gives a careful account of powder diffraction methods. A feature of an in- creasing number of papers is that ‘direct’ methods of phase determination which do not depend on the presence of a ‘heavy’ atom are being used for the analysis of both centrosymmetric and non-centrosymmetric crystals.Absolute configuration determination is also receiving attention and a second reference list of organic structures whose absolute configurations have been determined by X-ray methods has a~peared.~ Limitations on space have made it impossible to report all crystallographic papers published in 1968 and many have had to be left out of this report or given limited coverage. As in the 1967 Annual Report papers which give only brief details of constitution of e.g. natural products will be reported in other chapters and have been omitted here. In the account that follows details of bond lengths etc. are given where these are differences from ‘accepted’ values ;4 estimated standard deviations are given where appropriate in parentheses in units of the least significant digit of the quantity to which they refer.Carboxylic Acids and Related Compounds.-The geometry of hydrogen bonding in carboxylic acids which do not form centrosymmetric dimers has been surveyed’ and four main features are pointed out. (i) The identification of the carboxy oxygen atoms as to which is carbonyl and which is hydroxy is A usually unambiguous on the basis of reo < rCOH and C-C-OH < C-O. (ii) Deviations of acceptor oxygen atoms from the mean planes of the carboxy-groups lie between 0.051 and 0.379 8,;none is as large as the 0-549 8 reported for a centrosymmetric dimer by Jeffrey and Sax.6 The largest rotation of the 0* -* 0vector out of the carboxy-plane is only 8”.(iii) The acceptor oxygen atoms in the synplanar O=C-OH..-O system have C-OH...O G.H. Stout and L. H. Jensen ‘X-Ray Determination-A Practical Guide,’ Macmillan New York 1968. L. V. Azaroff ‘Elements of X-Ray Crystallography,’ McGraw-Hill New York 1968. F. H. Allen S. Neidle and D. Rogers Chem. Comm. 1968,308. Chem. Soc. Special Publ. No. 18 1963 41. J. Donohue Acta Cryst. 1968,24 B,1558. ‘G. A. Jeffrey and M. Sax Acta Cryst. 1963 16,430. George Ferguson angles in the range 1085 to 131.9".(iv) There is no apparent regularity with regard to the positions of the donor OH groups most of which are not even approximately synplanar and the angles C=O.*.HO range from 118.8 to 168". It follows that invocation of sp2 hybridization and localised electron pairs to explain the planarity of centrosymmetric carboxylic acid dimers is unnecessary and that in the case of some acids which do not form dimers this theory leads to the wrong prediction.The hydrocarbon chain of DL-2-methyl-7-oxododecanoicacid7 is bent at C(2) and the methyl group forms a continuation of the zig-zag backbone; conformations of this type are common in methyl branched fatty acids. The chain is also twisted 7"at the keto-group. The mean C-C distance 1-51l(11) 8 and C-C-C angle 114.2(7)"are systematically shorter and larger respectively than normal and are explicable in terms of thermal anisotropy and rotatory oscillations of the chains about their long axis. The structure of the cr-form of brassylic acid CO,H(CH,) 1C02H has been determined' and compared with the structure ofpirnelic(C,) azelaic (C9) and undecanoic (C dicarboxylic acids.These acids have a constancy of molecular conformation in particular of the carboxy-groups and hydrogen bonds and a characteristic form of packing. Interest in systems with 'very short" hydrogen bonds continues. Hydrazinium hydrogen oxalate has been studied by X-ray" and neutron" diffraction and the results are in good agreement ;the hydrogen oxalate ions are linked end-to- end by short hydrogen-bonds determined as 2.450(4)A by X-rays and 2.448(7) 8 by neutrons. These bonds are either truly symmetrical or have statistically disordered hydrogen atoms. Other X-ray analyses of acid salts also thought to contain genuinely symmetrical 0* * H - - - 0 bonds include potassium hydrogen bisphenylacetate [O-.H...02-443(4)A],12 potassium hydrogen di-p-hydroxy- benzoate hydrate [2.458(6) potassium hydrogen malonate [2.459(7) 8,],14 and potassium hydrogen di-p-methoxybenzoate [2.476( 18) A].' In all these examples the oxygen atoms involved in the O..-H..-Obonds are crystallo- graphically equivalent being related by either two-fold axes or centres of symmetry. In potassium hydrogen diformate however,' two crystallographic- ally non-equivalent formate groups are linked into a dimer by a short possibly symmetrical hydrogen-bond with 0.* 0 2-447(6)A. There are no short sym- metrical hydrogen-bonds in the crystal structure of potassium hydrogen gly- collate. The absolute configuration of the biologically active isomer ( +)-isocitric ' A.M. O'Connel Acta Cryst. 1968,24 B 1399. * J. Housty Acta Cryst. 1968 24 B 486. J. C. Speakman Chem. Comm. 1967,32. lo N. A. K. Ahmed R. Liminga and I. Olovsson Acta Chem. Scad. 1968,22,88. A. Nilsson R. Liminga and I. Olovsson Acta Chem. Scad. 1968,22 719. L. ManojloviC and J. C. Speakman Acta Cryst. 1968,24 B 323. l3 L. ManojloviC Acta Cryst. 1968 24 B 326. l4 G. Ferguson J. G. Sime J. C. Speakman and R. Young Chem. Comm. 1968,162. l5 D. R. McGregor and J. C. Speakman J. Chem. SOC.(A),1968,2106. l6 G. Larsson and I. Nahringbauer Acta Cryst. 1968,24 B 666. R. F. Mayers E. T. Keve and A. C. Skapski J. Chem. SOC.(A),1968 2258. X-Ray Crystallography acid has been determined as (1R :2S)-l-hydroxy-1,2,3-propanetricarboxylic acid from an investigation of its potassium dihydrogen salt.'* The ion is fully extended and it is the central carboxy-group which is ionised.Three tartrates odium,'^ calcium and strontium,20 have been examined as part of a study of the conformation of the tartrate ion in the crystalline state; the two halves of the ions each consisting of a carboxy-group a tetrahedral carbon and a hydroxy oxygen atom are individually planar. Two crystalline modifications of DL-a-aminobutyric acid have been studied.2 In the monoclinic form the y-carbon atom is distributed mainly among three positions corresponding to the three rotational isomers trans gauche (I) and gauche (II) with respect to the nitrogen atom; in the tetragonal form the y-carbon is located only at the trans-position.The conformation of the a-form of a-glycylglycine kH3 CH CO NH -CH -COY is different from that found for the p-form;22 there is an angle of 22" between the plane of the amide group and that of the carboxy-group in the a-form whereas in the p-form these groups are coplanar. The distortion in the a-form presumably permits better packing and stronger hydrogen-bonds and van der Waals interactions. In the asym- metric unit of crystals of L-cysteine there are two independent molecules which NH.PO,H, I C=NH I CH,-N-CH2COOH l8 D. van der Helm J. P. Glusker C. K. Johnson J. A. Minkin N. E. Burow and A. L. Patterson Acta Cryst. 1968 24 B 578. l9 G. K. Ambady and G. Kartha Acta Cryst. 1968,24 B 1540.2o G. K. Ambady Acta Cryst. 1968,24 B 1548. 21 T. Ichikawa and Y. Iitaka Acta Cryst. 1968,24 B 1488. T. Ichikawa Y. Iitaka and M. Tsuboi Bull. Chem. SOC.Japan 1968,41 1027. 22 A. B. Biswas E. W. Hughes B. D. Sharma and J. N. Wilson Acta Cryst. 1968 24 B 40; E. W Hupheq. Actn Crw. 1968. 24. B. 1 128 George Ferguson occur as zwitterions HSCH *CHNH3*CO; .23 The bond lengths and angles are not significantly different from each other or from accepted values but their conformations differ by twists of 118" around the C(a)-C(p) bond and 33" around the C-C(a) bond. In L-aspartic acid the ionised and non-ionised carboxy-groups can be clearly distinguished showing the zwitterion to be O,C* CHhH CH C02H.24Thetrans-isomerof4-aminomethylcyclohexane-carboxylic acid which exhibits strong antifibrinolytic activity.has the zwitterion in the di-equatorial c~nformation.~' N-Phosphoryl creatine (11 a biological high-energy phosphate serves as an energy reservoir in vertebrate muscles and crystals of its disodium salt have been examined.26 The guanidino-group is planar and all hydrogen atoms available for hydrogen bonding are used. Observed differences between bond distances found in (1)and in creatine are not significant and the structural basis of the instability of (1) remains unresolved. 0-Carbamoylhydroxylamine OC(NH,)*ONH, is planar with the exception of the hydrogen atoms of the 0-bonded amino-gr~up.~~ The amide group of NN-diphenylacetamide is planar and the two phenyl rings are inclined at 62" (ring nearest oxygen) and 77" to the amide plane.28 The atoms of the ester groups of the centrosymmetric molecule 1,1,2,2-tetracarbomethoxyethaneare planar in the crystalline state in agreement with vapour and liquid-phase investigation^.^^ The octabutyrate C,4H,4Br40 obtained from condensation of resorcinol and p-bromo- benzaldehyde and acylation of the phenolic product has structure (2).30The four carbon atoms linking the aromatic rings are nearly coplanar and the bromo- phenyl groups are all directed to the same side of that plane.The carbanion in potassium 4,4-dinitro-2-butenamide is essentially planar and the NCN bond angle is 120" in spite of an O...O distance of only 2.51 8 between the nitro- groups.31 Chloro- and bromo-cyanoacetylene form linear chain structures with N C1 and N --Br distances of 2.970(8)and 2-956(18) A re~pectively.~~ Bonded distances for the chloro- and bromo-compounds are respectively :C-halogen 1.634(9) 1*766(15); CsC 1*176(12) 1*190(21); =C& 1.382(13) 1*399(22); -C=N 1.133(13) 1.113(24)A.The shortening of the C=N distances from the value 1.158(1) for gaseous cyanides appears to be real when compared with similar non-metallic cyanides where the nitrogen is involved in donor-acceptor interaction. Molecules of bigeranyl tetrahydrochloride (2,6,11,1S-tetrachloro-2,6,11,15-tetramethylhexadecane)are almost planar centro~ymmetric.~~ The carbon chain is bent at the tertiary carbon atoms thereby achieving a pro- *' M. M. Hardincg and H. A. Long. Acta Cryst..1968. 24. B. 1096. 24 J. L. Derissen H. J. Endeman and A. F. Peerdeman Acta Cryst. 1968,24 B 1349. 25 P. Groth Acta Chem. Scad. 1968,22 143. 26 J. R. Herriott and W. E. Love Acta Cryst. 1968,24 B 1014. 27 1. K. Larsen. Actn Chm. Scnnd.. 1968. 22. 843. 28 W. R. Kngbaum R.-J. Roe and J. D. Woods. Acra Crvr.. 1968. 24. B. 1.704. 29 J. P. Schaefer and C. R. Costin J. Org. Chern. 1968,33,1677. 30 B. Nilsson Acta Chem. Scad. 1968,22 732. 31 J. R. Holden and C. Dickinson J. Amer. Chem. SOC. 1968,90,1975. 32 T. Bjorvatten Acta Chem. Scad. 1968,22,410. 33 F. Mo and H. Serrum Acta Cryst. 1968,24. B 605. X-Ray Crystallography 45 nounced Z-shape. The C-Cl bonds pointing out of this plane are abnormally long [mean 1-857(7) A] ;the main reason for this is believed to be short intra- molecular Cl-H approach distances.The C1-C-C angles are in the range 105.3-107.6(4)". Substituted Benzene and Polycyclic Aromatic Compounds.-The carboxy-group in rn-bromobenzoic acid is almost exactly coplanar with the benzene ring34 unlike that of the ortho-substituted derivative. The crystal structure of o-aminobenzoic acid contains two non-equivalent molecules one neutral and the other a zwitterion. In both the carboxy-group is rotated about the exocyclic C-C bond.35 The nitro-group in 3-nitroperchlorylbenzeneNO2 C6H4 C10 is rotated 13" from the plane of the aromatic ring and decreased. resonance interaction contributes to a long C-N distance of 1.497(10) A; the C-C1 distance 1*786( 10) A is also long compared with that for a C-Cl bond where the chlorine is uns~bstituted.~~ Another effect noted is that the C-C-C angles [124.1 and 126-1(6)"] at substituted carbon atoms are significantly greater than 120".2,6-Dimethyl-4-methoxylbenzonitrile N-oxide is planar apart from the methoxy-carbon atom with the C-N-0 bond angle reported as 178.3(6)". The bond lengths in the C-C-N-0 chain are 1.435 1.147 and 1-249(8) A respectively and compare with MO predi~tion.~'The catechol moiety in the hydrochloride of dopamine 3,4-dihydroxyphenylethylamine is planar and the C-N distance agrees well with the average value 1.503 A for C-GH bonds in a-amino-a~ids.~~ When pale yellow crystals of 2-(2',4'-dinitrobenzyl) Br Ph (3) (4 1 pyridine (3) are irradiated with light of 4000 A or less a deep blue substance is produced by what is believed to be a reversible tautomeric reaction.The methylene hydrogen atoms in (3)are presumably the most acidic in the structure and the most likely to be involved in the tautomerisation reaction. In crystals of (3) the intramolecular C-C-C angle between the two aromatic rings is 114" and the closest approach of a methylene hydrogen atom to an electronegative atom is intramolecular to an oxygen (at 2.4 A) on the o-nitro-group. This nitro- group is rotated 32" and the other through 12" from the benzyl plane. It is suggested that the tautomerisation is probably intramolecular and begins 34 N. Tanaka T. Ashida Y. Sasada and M. Kakudo Bull. Chem. SOC.Japan 1967,40,2717. 35 C. J. Brown Proc.Roy. SOC. 1968 A 302,185. 36 G. J. Palenik J. Donohue and K. N. Trueblood Acta Cryst. 1968,24 B 1139. 37 M. Shiro M. Yamakawa T. Kubota and H. Koyama Chem. Comm. 1968,1409. R.Bergin and D. Carlstrom Acta Cryst. 1968,24 B 1506. George Ferguson with the transfer of a methylene hydrogen atom to an oxygen of the o-nitro- group leaving the two rings interconjugated. This hydrogen atom might then be transferred intramolecularly to the pyridine nitrogen atom.39 Complete details of the structure of 2,4,6-trinitrophenetole have appeared4' and also those of its complexes with caesium and potassium ethoxide4' (Meisenheimer salts) M+[C,H,(NO,),(OEt),] -. In both complexes the two equivalent alkoxy-groups are attached to the same carbon atom which attains tetrahedral configuration with mean C-C-C angle 107" ; the six-membered ring retains planarity.The intramolecular strain in 1,2,4,5-tetra-t-butylbenzene is relieved by angle deformation rather than out-of-plane distortion of the ring.42 The molecule has a crystallographic centre of symmetry and mutual repulsion of the o-butyl groups increases the appropriate angles e.g. C(2)-C(l)-C(butyl) at C(1)and C(2) to ca. 130". Since the aromatic ring stays planar the internal angle at C(3) is also increased to 130". The bonds connecting the t-butyl groups to the ring are long (1.567 A) compared with similar bonds in other compounds and this may also be an overcrowding effect. Crystals of chloropentamethylbenzene exhibit an orientational disorder the chlorine atom and methyl groups being distributed in six possible positions.43 All benzene rings in hexaphenylbenzene are essentially planar but the molecule is distorted as a result of out-of-plane bending of exocyclic The non-centrosymmetric molecule adopts a propeller like conformation with approximate six-fold symmetry ; the peri- pheral rings are not perpendicular to the central ring but are twisted about 25" from this position and the CLC bridge distances vary from 1.473 to 1-531(13) A).Another polyphenylbenzene slightly less overcrowded is obtained on dimerisation of the 3-bromo-2,4,6-triphenylphenoxyl radical and has structure (4).45 HO 39 K. Seff and K. N. Trueblood,Acta Cryst. 1968,24 B 1406. 40 C. M. Gramaccioli,R. Destro and M. Simonetta,Acta Cryst.1968 24 B 129; Chem. Comm. 1967. 331 ;Ann. Reports. (B),1967 72. 41 R. Destro C. M. Gramaccioli and M. Simonetta,Acta Cryst. 1968 24 B 1369; c$ H. Ueda N. Sakabe J. Tanaka and A. Furusaki Nature 1967,215,956; Ann Reports (B),1967,72. 42 k van Bruijnsvoort L. Eilermann H. van der Meer and C. H. Stam Tetrahedron Letters 1968,2527. " G.-P. Charbonneau and J. Trotter J. Chem SOC.(A) 1968 1267. 44 J. C. J. Bart Acta Cryst. 1968 24 B 1277. 45 R. Allmann and E. Hellner Chem. Ber. 1968,101,2522. X-Ray Crystallography Me Me The structures of 2'-fl~0r0-~~ and 2'-chlor0-4-acetyl-biphenyl~~have been reported. The angles between the phenyl rings are 51 and 49" respectively and the C(sp2)-C(sp2) single bonds are 1.479(10) and 1.490(10) A.Although no major o-substituents are present in 3,3'-dimeth~l-~~ and 3,3'-dichloro-4,4'- diamino-bipheny14' the phenyl rings are not coplanar but are inclined at 41 and 21" respectively. The C(sp2)-C(sp2)bonds are 1.504(13) and 1.515(24) A. In addition in each molecule each phenyl ring is bent through ca. 3" away from the line of C(1)-C(1'). Ellagic acid (5) the (centrosymmetric) dilactone of 2,2'-dicarboxy-4,S,6,4',S',6'-hexahydroxybiphenylis essentially planar only the lactone carbonyl groups being slightly tilted (3.6")from molecular plane." 8,16-0xido-cis-[2.2]metacyclophane (6)has the m symmetry demanded by its space group but the molecule has nearly mm symmetry and is folded to a dihedral form with an angle of 99-6" between the slightly boat-shaped benzene rings.51 The bond angle at the oxygen atom is 1014(4)O while the mean value of those in the methylene bridges is 119.0(5)".The strain implied by these values is consistent with the tendency of the compound to eject the hetero-atom and transform into the corresponding pyrene. A centre of symmetry is required of 4,12-di(bromomethyl)[2,2]metacyclophane (7) by its space group and the two benzene rings are displaced stepwise and slightly distorted to a boat-shape to accommodate the intramolecular overcrowding effects in this molecule52 as in 46 D. W. Young P. Tollin and H. H. Sutherland Acta Cryst. 1968,24 B 161. 47 H. H. Sutherland and T. G. Hoy Acta Cryst. 1968,24 B 1207. 48 S. A. Chawdhury A. Hargreaves and R. A. L. Sullivan Acta Cryst.1968,24 B 1222. 49 S. A. Chawdhury A. Hargreaves and S. H. Rizvi Acta Cryst. 1968,24 B 1633. 50 A. McL. Mathieson and B. J. Poppleton Acta Cryst. 1968,24 B 1456. 51 M. Mathew and A. W. Hanson Acta Cryst. 1968,24 B 1680. 52 M. Mathew. Acra Crvst.. 1968.24. B,530. 48 George Ferguson the parent 4,12-dimethyl deri~ative.’~ The CH,-CH bond length is 1.568(8) A which is comparable with 1-573 A in the parent and is also indicative of molecular strain. 9-Dicyano-2,7-dinitrofluorene (8) has two-fold (crystallographic) symmetry; the fluorene moiety is planar and the nitro-groups are rotated 17.6” b~t-of-plane.’~ The dicyanomethylene portion is rotated 2.3” about the formal double-bond almost exactly the same conformation as found in 9-dicyano-2,4,7-trinitrofluorene’’(which in addition has the fluorene moeity in a slight propeller conformation because of overcrowding at the 4-nitro-group).The seven-membered ring of dibenzo[b,f]tropone (9) is in boat conformation similar to that in cycloheptatriene with the two benzene rings inclined to each other at an angle of 39°.56 The serendipitous synthesis of (10) from a-phenyl- cinnamoyl chloride and its X-ray analysis have been rep~rted.’~ The novel reaction results in the formation of four new carbon-to-carbon bonds and structure (10) can be defined by two planes intersecting along the Ph-C-CH bond. Molecules of 9-anthraldehyde dimer lie on symmetry centres and hence the CHO groups are in the trans-configuration with respect to the anthracene ~keleton.’~ Each half-molecule is bent through an angle of 46” similar to that found in di-p-anthra~ene.’~ Tricarbonylchromium complexes of a number of aromatic hydrocarbons or their derivatives have been prepared and studied crystallographically including those of l-aminonaphthalene,60 anthracene,61 phenanthrene,62 and 9,lO-dih~drophenanthrene.~~ In the 1-aminonaphthalene complex the tricarbonylchromium moiety is located over the unsubstituted ring and the orientation of the carbonyl groups in all four complexes resembles the staggered conformation of benzenetricarbonylchromium.The anthracene phenan- threne and dihydrophenanthrene complexes have the chromium atom bonded to a side ring and small but significant lengthening of the C-C bonds in this ring is found ;there is however no suggestion of alternation of long and short bonds as a result of the complexing to chromium.3,5,8,10-Tetramethylaceheptalene(1 l) a hydrocarbon with a 14 x-electron system is planar except for the methyl hydrogen atoms;64 the bond distances and angles are in good agreement with quantum-mechanical predictions. Non-aromatic Carbocyclic Molecules-Bicyclopropyl adopts the trans con-53 A. W. Hanson Acta Cryst. 1962,15,956. 54 J. Silverman A. P. Krukonis and N. F. Yannoni Acta Cryst. 1968,24,8 1481. 55 J. Silverman A. P. Krukonis and N. F. Yannoni Acta Cryst. 1967,23 1057. 56 H. Shimanouchi T. Hata and Y. Sasada Tetrahedron Letters 1968,3573. 57 A. L. Bednowitz W. C. Hamilton R Brown L. G. Donaruma P. L. Southwick R Kropf and R k Stanfield J.Amer. Chem. SOC.,1968,90,291. 58 M. Ehrenberg Acta Cryst. 1968,24 B 1123. 59 M. Ehrenberg Acta Cryst. 1966,20 177. 6o 0.L. Carter A. T. McPhail and G. A. Sim J. Chem. Soc. (A),1968,1866. 61 F. Hank and 0.S. Mills J. Organometallic Chem. 1968 11 151. 62 K. W. Muir G. Ferguson and G. A. Sim J. Chem. SOC. (B),1968,467. 63 K. W. Muir and G. Ferguson J. Chem. Soc. (B) 1968,476. 64 E. Carstensen-Oeser and G. Habermehl Angew. Chem. 1968,80,564. X-Ray Crystallography formation in the crystal with 2/m symmetry; the average cyclopropyl C-C bond-length is 1.506(4)8 and the central bond 1-487(4) The C-C bonds in the cyclopropane ring of tri-isopropylidenecyclopropane(12) have length 1.44(1) 8, shorter than in bicyclopropyl because of the three ethylenic bonds radiating from the ring., Me Me 0 0 (16) (15) Cyclobutane rings occur in planar and puckered conformations in the solid state.Planar molecules are invariably found in centrosymmetric space groups with the molecular and crystallographic centres of symmetry coinciding. In the puckered conformation dihedral angles commonly range from 145 to 160" and there are positions analogous to the equatorial and axial positions of cyclohexane; in the planar conformation all positions are equivalent.,' The disodium salt of trans-1,3-cyclobutanedicarboxylicacid crystallises with two neutral acid molecules of crystahation Na,+C4H,(C0,),,2C4H,(C0,H), and the surprising result of an X-ray is that the neutral acid molecule which has a planar centrosymmetric ring when crystallized by itself,,* has a puckered ring with dihedral angle 155" while the dianion occupies a centre of 65 J.Eraker and C. Rsmming Actu Chem. Scad. 1967,21,2721. 66 H. Dietrich and H. Dierks Angew. Chem. 1968,80,487. 67 E. Adman and T. N. Margulis J. Amer. Chem SOC. 1968,90,4517. T. N. Margulis and M. S. Fischer J. Amer. Chem. SOC 1967,89,223. 50 George Ferguson symmetry and is therefore planar. The C-C single-bonds in the dianion average 1-563(9) A while those of the di-acid average 1.552(9) A. Tetra~yano-~' and octahydroxy-cyclobutane70molecules lie on symmetry centres in their crystals and are planar. The tetracyano-derivative is the cis-trans-cis isomer with ring bond-lengths 1.561(3) and 1.547(3) A the longer bond being between the atoms with a czs-arrangement of cyano-groups.In the octahydroxy- derivative the mean C-C bond-length is 1-562(4) A. The dihedral angles of the strained cyclobutane derivative (13) are 120" and the C-C-C angles are 87" at the bridgeheads and 75" at the other two carbon The conformations of the three cis-1,2-dihalogenobenzocyclobutenes(14) (X = C1 Br or I) are essentially similar with the cyclobutene ring planar rather than skewed and coplanar with the benzene ring plane within l.S".72 The brominated photo- dimer of 1,4-naphthoquinone 1,2,3,4-tetrabromo-1,2,3,4-diphthaloylcyclo-butane (15) has the anti-conformation in the solid state. A crystallographic two-fold axis coincides with the molecular two-fold axis (through the mid- points of the bonds linking the two halves of the molecule) and the cyclobutane ring is puckered.73 In the solid state 4,4-diphenylcyclohexanoneadopts a chair conformation in which the carbonyl end of the molecule is severely flattened ;74 the angle be- tween the planes C(2)C(l)C(6) and C(3)C(4)C(5) is 14" (in undistorted cyclo- hexane it is zero).The six-membered ring of cyclohexane-1,4-dione dioxime has the 'twisted boat' conformation and the molecule has nearly two-fold sym- metr~.~ Moleculesof 2,3-bis-( cis-4-chloro- l-methylcyclohexyl)-trans-but-2-ene (16) in the crystalline state present a case of intramolecular conformational isomerism in as much as the two cyclohexane rings exhibit chair conformations of opposite type in one ring the chlorine is equatorial whilst in the other it is axial.G (17) Me 2 69 B. Greenberg and B. Post Acta Cryst. 1968,24 B 918. 'O C. M. Bock J. Amer. Chem. Soc. 1968,90,2748. " A. Padwa E. Shefter and E. Alexander J. Amer. Chem. Soc. 1968,90,3717. '' G. L. Hardgrove L. K. Templeton and D. H. Templeton J. Phys. Chem. 1968,72,668. 73 G.J. Kruger and J. C. A. Boeyens J. Phys. Chem. 1968,72,2120. 74 J. B. Lambert R. E. Carhart P. W. R. Corfield and J. H. Enemark Chem. Comm. 1968,999. 75 P. Groth Actu Chem. Scud. 1968,22 128. 76 D. Mootz Acta Cryst. 1968 24 B 839. 51 X-Ray Crystallography c1 c1 R' Br :() 4 R2 (20) (21) In racemic crystals of geijereneesilver nitrate CI2H,8r 2AgN0 (17) the cyclohexene ring has a half-chair conformation with one carbon atom on each side of the planar four carbon (CHR-CH=CH-CH2) segment.The iso- propyl group is not planar and is trans to the vinyl group. Both groups associate with the same silver atom; another silver atom is associated with the cyclo- hexene double bond.77 The polyene canthaxanthin 4,4'-diketo-P-carotene (18),has a crystallographic centre of symmetry at the middle of the C(15)-C( 15') double-bond and the all-trans configuration of the conjugated bond system is interrupted at the cyclohexenone rings. The dihedral angles between the planes of the rings and the chains are 43" from s-ci.~.~~ When the central double-bond in (18) is converted to a triple bond to give 15,15'-dehydrocanthaxanthin,with the exception of the approximate s-cis orientation about the single bond from the chain to the cyclohexene rings the double-bond system again retains the all- trans configuration.The dihedral angle between the planes of the ring and chain is 28°.79 The eight-membered ring of trans-syn-trans-1,2,5,6-tetrabromocyclo-octane possesses a twisted crown conformation one of the predicted favoured con- formations for eight-membered rings. The C-C-C bond angles are all sig- nificantly greater than tetrahedral (mean value 118"). Results of dipole moment and n.m.r. investigations are in accord with the predominance in solution of one conformer and are compatible with this being the twisted crown found in the solid state." From a consideration of space-group symmetry requirements and unit-cell parameters it has been deduced'' that cis,cis-cyclo-3,8-diene-1,6-dione must possess a chair conformation (19) in the solid state.This is an example unfortunately all too rare in which useful information can be deduced without recourse to intensity measurements and extensive calculations. The conformation of 6-oxononanolide (oxycyclodeca-2,7-dione)82is similar to that observed in several cyclodecane derivatives' with the ring oxygen and carbonyl groups so situated as to minimise the number oftransannular H... H contacts. In " D. J. Robinson and C. H. L. Kennard Chem. Comm. 1968,914. 78 J. C. J. Bart and C. H. MacGillavry,Acta Cryst. 1968,24 B,1587. 79 J. C. J. Bart and C. H. MacGillavry,Acta Cryst. 1968,24 B 1569.G. Ferguson D. D. MacNicol W. E. Oberhansli,R. A. Raphael and J. A. Zabkiewicz Chem. Comm. 1968 103. H. L. Carrell B. W. Roberts J. Donohue and J. J. Vollmer J. Amer. Chem Soc. 1968,90,5263. 82 W. Fedeli and J. D. Dunitz Helv. Chim. Acta 1968 51,445. *' J. D. Dunitz and H. P. Weber Helo. Chirn. Acra 1964,47.951. and refs. therein. 52 George Ferguson large rings opportunities for transannular interaction are decreased and in cyclotetratriacontane [CH,] 34 the conformation is made up basically of two parallel zig-zag chains of 15 atoms linked at each end by two closure atoms conforming to a path traceable in the diamond lattice. Small twists and bond distortions occur in the side chains as a result of steric hindrance at the closure atoms.84 The pyrolytic reaction of perchloro-3,4-dimethylenecyclobutene gives at least four isomeric compounds of formula C12C11285 and yet another compound has been isolated from the reaction but this time with formula Cl2Cll4 (20).The molecule has two-fold crystallographic symmetry (the two-fold axis runs through the two ClC-CCl portions of the ring) and the cyclo-octatriene ring has a somewhat distorted tub conformation. Any two adjacent double-bonds out of the five do not lie in a plane and hence there will be no strong conjugation between them.86 Five isomerides of perhydroanthra-cene have been predicted two of which can be centrosymmetric. The isomer of m.p. 121"c is one of these and the configuration is cis-cis as referred to the single hydrogen atoms on the central ring.87 The mean value of the C-C-C bond angle is 111.5(2)".Two derivatives of bicyclo[2,2,2]octane (21) have been examined in an attempt to determine the preferred conformation of this system (crystals of the parent molecule are disordered). In the derivative (21; R' = p-BrC6H,-S02*CH2,R2= H)88 the carbon skeleton conforms to D symmetry with the group of atoms C(2)C(7)C(6) rotated 3" about the C(l) to C(4) axis with respect to the C(3)C(S)C(S) group. This has the effect of increasing the torsional angles at the C(2)-C(3) type bonds to 5" whereas with an eclipsed D, model a zero value would hold. In the disubstituted derivative (21; R' =R2 = C02H),89 however a non-twisted carbon skeleton with D, symmetry is found. 1-Bromotriptycene (22) has three-fold symmetry but there is also probably some disorder in its crystals.The C-Br distance is 1.97 A and the bridging C-C bonds have length 1.53 A at the bromine end and 1.51 A at the hydrogen indicating no conjugation between the aromatic rings." Ph. CO I (23) 84 H. F. Kay and B. A. Newman Acta Cryst. 1968,24 B 615. A. Furusaki Bull. Chem. SOC. Japan 1967,40,2518. 86 A. Furusaki and I. Nitta Tetrahedron Letters 1968 1379. 87 K. E. Hjortaas Acta Chem. Scad. 1967,21,2261. A. F. Cameron G. Ferguson and D. G. Morns Chem. Comm. 1968 316; J. Chem. SOC. (B) 1968,1249. 89 0.Ermer and J. D. Dunitz Chem. Comm. 1968,567. 90 K. J. Palmer and D. H. Templeton Acta Cryst.. 1968,24 B. 1048. X-Ray Crystallography 53 Whereas simple bicyclo[3,3,l]nonanes lacking substituents at positions 3 and 7 adopt flattened twin-chair conformations the derivative (23) is an example with a boat-chair conformation ;the distortion from ideal cyclohexane geometry is less than that in the twin-chair bicycl0[3,3,l]nonanes.~~The tri- cyclo[5,3,1,12~ 6]dodecane derivative (24) adopts a distorted double-chair conformation in spite of the exo-hydroxy-group at C( 12); however the hydroxy- hydrogen is held well clear of the methylene hydrogen at C(11) by an inter- molecular O-H...0bond to the carbonyl oxygen ofaneighbouring molecule.92 A short note9 andaf~llpaper~~ on the structure ofbullvalene(25) have appeared but a& by different research groups. In contrast to its behaviour in solution bullvalene shows no valence-isomerization in the solid state.Mean molecular dimensions from the full report94 are C-C(cyc1opropane) 1.539(7) C(sp')- C(cyc1opropane) 1.452(7) C=C 1-3 19(7) and C(sp')-C(apex) 1*508(7)A. Structure (26) for the novel cage molecule 3,4,5-trichlorotetracyclo[4,4,0,03~ 9 049 *]decan-2-one has been confirmed and the stereochemistry at C(5) de- termined. The cyclobutane ring is planar but the cyclopentane rings are puckered with internal angles varying between 97 and 106". The two cyclohexane rings are in boat form with internal angles close to tetrahedral (108-111") except for those at C(2). C(3 C(7) and C(l0)which are close to Nitrogen- Sulphur- and Oxygen-containing Hetero-compounds and Sugars.- A refinement of the structure of "'-dinitroethylenediamine reveals that the C-N distance is normal [1.463(4)A] but the N-N distance is abnormally short [1.301(4)A].Strong dipole-dipole interactions are suggested as the predominant crystal binding force.96 Methylglyoxalbisguanylhydrazone NH -C(NH). NH.C(CH,).CH -N.NH-C(NH)*NH,. which has marked activity toward human acute myelocytic leukaemia has been studied by X-ray and neutron diffraction in the form of the dihydrochloride monohydrate C5H12N8,2HCl,H20.97 The results are in good agreement with respect to the parameters of the non-hydrogen atoms. The hydrogen atoms were located precisely by the neutron diffraction study and the average apparent C-H N-H and 0-H bond-lengths are 0.1 A longer than those found in the X-ray study.In the crystals the dipositive ion C5H14Ng+ is planar and has a com- pletely trans-configuration of the chain. Methanesulphonanilide C6H NH SO2 CH, is related to a series of compounds with blood-pressure control activity. The aminohydrogen clearly sticks out alone on one side of the phenyl ring while the methylsulphone group is on the opposite side of the plane. The amino-hydrogen ofthe monomer is thus readily available to a receptor molecule during biological action.98 91 C. Tamura and G. A. Sim J. Chem. SOC. (B),1968,1241. 92 G. Ferguson and W. D. K. Macrosson J. Chem. SOC.(B) 1968,242. "S. M. Johnson J. S. McKechnie B. T.-S. Lin and I. C. Paul J. Amer. Chem Soc. 1967 89 7123. 94 k Amit R. Huber and W. Hoppe Acta Cryst. 1968,24 B 865. 95 D.Schwarzenbach Actu Cryst. 1968,24 B 238. 96 J. W. Turley Actu Cryst. 1968,24 B 942. 97 W. C. Hamilton and S. J. La Placa Actu Cryst. 1968,24 B 1147. 98 H P.Klug Actu Cryst. 1968 24 B,792. George Ferguson Intermolecular distances N...C2-98 and N...S 3.22 A in crystals of tetra-cyanothiophen suggests weak donor-acceptor bonding between the mole- cule~.~~ The paper also gives a reference list of bond lengths and angles reported in various thiophen derivatives. The structures of three isomeric dithienyls C8HhS2and of P-thiophenic acid have been examined. 2,2'-Dithionyl (27) 0 II c1 (28) decomposes in the X-ray beam while 2,3'- and 3,3'-dithienyl and P-thiophenic acid (28) are disordered with the sulphur atom effectively occupying two sites because of rotation of the thionyl groups about the exocyclic C-C bond.'OO This situation is not at all uncommon with molecules of this type.Dibenzo- thiophen sulphone (29) has two-fold (crystallographic) symmetry and conforms closely to Czvsymmetry experimentally the C-S-C and 0-S-0 angles are 92 and 120" respectively. lo' 2,2'-Dichlorotrimethylenesulphite has con- formation (30) with the S=O group axial and the molecule has C,symmetry within the limits of error.Io2 Thiepin 1,l-dioxide exists in the flattened boat- conformation (31). The C(p)-C(y) type bonds are abnormally short (1.429 (31) 99 V. Rychnovsky and D. Britton Acta Cryst. 1968,24 B 725. loo G. J. Visser G. J. Heeres J. Wolters and A. Vos Acta Cryst. 1968 24 B 467. lo' L.R. Kronfeld and R. L. Sass Acta Cryst. 1968,24 B 981. lo2 J. W. L. van Oyen R. C. D. E. Hasekamp. G. C. Verschoor and C. Romers Acta Cryst. 1968 24 B 1471. 55 X-Ray Crystallography Me Me (35) 1.438 A),as are the C-S bonds (1-723,1.716 A) and suggest that some unusual bonding effects are being observed resulting in a flattening of the hydrocarbon portion of the ring. In agreement with this the internal bond-angles are some- what enlarged (C-%-C values range from 122-8-129.4" and C-C is 103.3°).103 The meso-ionic structure is found for the thiabenzene derivative (32)and the C-H adjacent to the sulphur atom is involved in an intermolecular hydrogen bond,C-H.-O=C /of3~12~.104Thefirstcrystal-structureanalysis \ of a bithiazole ring system shows that the molecule (33) is nearly ~1anar.l'~ The structure of the antibiotic anisomycin has been determined from an analysis of a N-acetylbromo-derivative.The molecule is the substituted pyrroli- dine (34) and an analysis of stereoelectronic factors governing ring-opening reactions of cyclopentane derivatives is also presented.Io6 The calcium salt of 2,6-pyridinedicarboxylicacid is found as the tri- and sesqui-hydrate. The crystal structure of the trihydrate (a bacterial spore metabolite) is built up of planar calcium dipicolinate dimers linked by water molecules. One of the hydrogen atoms of the pyridine ring forms a hydrogen bond to the carbonyl group of another dipicolinate ion [CH-..O 3-15(1) A],linking the ions into an infinite 103 H.L. Ammon P. H. Watts jun. J. M. Stewart and W. L. Mock J. Amer. Chem. SOC.,1968,90. 4501. Io4 C. Tamura S. Sato and Y. Kishida Tetrahedron Letters 1968 2739. G. Koyama H. Nakamura Y. Muraoka T. Takita K. Maeda H. Umezawa and Y. Iitaka. Tetrahedron Letters 1968,4635. J. P. Schaefer and P. J. Wheatley J. Org. Chem. 1968,33 166. George Ferguson ribbon by a ten-membered centrosymmetric ring with sequence ~H.-occcH.-oC~.~~~ Two structures (35)'" and (36),lo9 which are stable nitroxide radicals have been reported. The NLO bond-lengths are 1.26(4) and 1.31(2) A in (35) and (36) respectively and in both molecules the angles which the NIO bond makes with the C-N-C plane are comparable (21 and 24" respectively). In the tri-p- nitrophenylmethyl free-radical the C-C bond-lengths at the central carbon atom are 1.47(4) A.110 Ph Ph"3ph (37) (38) ph (39) 0I R (40) (41) (42) 'CI H (431 (44) (45 1 Interesting features of (37) include an intramolecular C-H ...N hydrogen bond (H...N is 2.15 and C.-.N 2-91 A) and a C-C-N angle of 81" within the four-membered ring.' l1 The pyrazoline ring in (38) is non-planar and N-N is 1.336 and N=C 1.333(7%; the dihedral angle between the planes of the phenyl rings is 1l0.ll2 The imidazoline ring of the hydrobromide of (39) is also sig- nificantly non-planar with C(17) lying 0.15 A out of the plane of the other four atoms.' 1,3-Diazepine-2-thione has conformation (40) with valency angles of 117" at the methylene carbon atoms and 131" at the nitrogen atoms; the lo' G.Strahs and R E. Dickerson Acta Cryst. 1968,24 B 571. Io8 J. LajzCrowicz-Bonneteau,Acta Cryst. 1968,24 B 196. Io9 D. M. Hawley G. Ferguson and J. M. Robertson J. Chem SOC.(B),1968,1253. P. Andersen and B. Klewe Acta Chem Scad. 1967,21 2599. 111 C. J. Fritchie jun. and J. L. Wells Chem. Comm. 1968,917. B. Duffin Acta Cryst. 1968 24 B,1256. J. S. McKechnie and I. C. Paul J. Chem. SOC.(B),1968.984. X-Ray Crystallography 57 dihedral angle between the [CH,] group and the CH,NNCH group is 127".l14A study of 1H-azepine in the free (41; R = SO2C6H4Br) and com- plexed (41; with Fe(CO) and R = C0,Me) state reveals that the free form and presumably closely related 1H-azepines are true polyenes.' ' The anti- biotic myxin has been confirmed as 1-hydroxy-6-methoxyphenazine5,lO-dioxide by a very precise analysis at -160"~~~~ A combination of bond- stretching and angle-bending is found in the overcrowded region of o-di-t-butylquinoxaline (42); the C(2)-C(3) bond is 1-475(6) A and angles of type C(2)-C(3)-C(15) are 130".'l7 In a paper on quaternisation reactions Lund and Gruhn describe a compound to which they ascribe formula (43) and this has been confirmed by X-ray analysis which reveals that the molecule is nearly planar.l1 A tetrazolopurine prepared from 6-hydrazinopurine by treatment with HNO has been shown to be (44),which is planar and packs with other molecules in planes 3-35 A apart. There is a close intermolecular C-H-a-N packing distance between molecules with C-..N 3.23 and H.-N 2-19 There are significant and symmetrical in-plane distortions of the benzene ring in saccharin o-6,H4SO2NH -CO and strain in the five-membered ring results in large angular distortions.The molecules are held in the crystal by strong N-H.-.O hydrogen-bonds 2.79 A.12o Dihydrouracil12' and dihydrothymine122 adopt half-chair conformations with the hydrogenated carbon atoms 0.3 to 0.35A out of the plane of the other ring atoms. In dihydrothymine the methyl group is equatorial. Both uracil and dimethylthymine dimers can be isolated from irradiated frozen solutions of the appropriate monomer. In the cis-syn-isomer of uracil (45)' 23 the cyclobutane ring has a dihedral angle of 155" and the heterocyclic rings are also not planar. Atoms C(5)and C(6) in each ring are -0.13 and +0-15A out of the ring plane and the rings are in addition twisted relative to one another by 24".Essentially the same type of structure is obtained on irradiation of dimethylthymine; the cyclobutane ring is markedly puckered (each carbon atom being 0.6 A out of the plane of the other three) and the two thymine residues are rotated relative to each other by 28G.124 Preliminary details of the structures of the 3',5'-cyclic phosphates of adenosine'25 and uridine' 26 have been given. M. Mammi A. del Pra and C. di Bello Ricerca sci. 1967,37 766. I. C. Paul S. M. Johnson L. A. Paquette,J. H. Barrett and R J. Haluska J. Amer. Chem Soc. 1968,90,5023. A. W. Hanson Acta Cryst. 1968,24 B,1084. G. J. Visser A. Vos A.de Groot and H. Wynberg J. Amer. Chem. SOC.,1968,90,3253. M. S. Lehmann and S. E. Rasmussen Acta Chem. Scad. 1968,22 1297. J. P. Glusker D. van der Helm W. E. Love J. A. Minkin and A. L. Patterson Acta Cryst. 1968,24,B,359;cf ref 111. lz0 J. C. J. Bart J. Chem. SOC.(B),1968 376. 12' D.Rohrer and M. Sundaralingam Chem. Comm. 1968 746. 12' S.Furberg and L. H. Jensen J. Amer. Chem. SOC.,1968,90,470. 123 E.Adman h4. P. Gordon and L. H. Jensen Chem Comm. 1968 1019. N.Camerman and A. Camerman Science 1968,160 1451. 125 K.Watenpaugh J. Dcw L. H. Jensen and S. Furberg Science 1968 159,206. lZ6 C.L.Coulter,Science 1968 159 888. George Ferguson The dimensions of the peroxide bond in various organic molecules including 4,4'-dibromo- and 4,4'-dichlorodibenzoyl peroxide have been compared.Six independent determinations of the peroxide bond-length have a mean value 1-47A. The peroxide dihedral angle by contrast appears strongly dependent upon its environment and values from 81 to 139" have been As part of a study of the geometry of cyclic organic peroxides the structures of (46),128 Y OH OH 0 -CH OH I OH OMe (49) (50) and (47; n = 5-7),12' have been described. The 0-0 distances lie between 1-47 and 1-48 A. In(47) the environment of the spiro-carbon atoms is asymmetric probably caused by intramolecular repulsion between hydrogen and oxygen atoms. In (47; n = 6)130 the cycloheptylidene rings have the chair form w mean C-C-C angle 115-3" while in (47; n = 7)131 the cyclo-octylidene ri conformation corresponds to 'boat-chair' and the average C-C-C angle is 116.5".The carboxy-groups in furan-a,a'-dicarboxylic acid are twisted 4" out of the furan-ring plane.132 The structure of a compound C12H200,derived from methoxyacetylene has been determined as the dioxa-admantane (48). The molecule has a two-fold crystallographic axis through the 0x3-oxygen atoms and the geometry of the skeleton is very similar to that of adamantane.133 L-Ascorbic acid 'vitamin C' (49) has been investigated by X-ray134 and neutron135 diffraction. The enediol group is planar and the average C-0-H 12' S. Caticha-Ellisand S. C. Abrahams Acta Cryst. 1968 24 B 277. P' Groth Acta Chem. Scad. 1967,21,2711. 129 P. Groth Acta Chem. Scad. 1967,21,2608.P. Groth Acta Chem. Scad. 1967,21,2631. 13' P. Groth Acta Chem. Scad. 1967,21,2695. E. Martuscelli and C. Pedone Acta Cryst. 1968,24 B 175. J. A. Kanters and J. B. Hulscher Rec. Trav. chim. 1968,87,201. 134 J. Hvoslef Acta Cryst. 1968 24 B 23. J. Hvoslef Acta Cryst. 1968,24 B 1431. X-Ra y Crystallography 59 angle in it is 113-9" while the alcohol C-0-H angle is 109.2"; the average C-C-H and 0-C-H angle is also 109.2". Molecules of DL-arabinitol C,H,(OH),136 and galactitol C,H,(OH),13' have planar zig-zag carbon chains with oxygen atoms above and below the plane; all oxygen atoms are involved in hydrogen bonding. The A'-and B- forms of D-mannitol have essen- tially the same conformation in their crystals with approximate two-fold symmetry and a planar carbon chain.The dimorphism is due to different systems of hydrogen bonding.' ''Another form of D-mannitol labelled K was obtained accidentally and it transpires that it has the same conformation as the B-form with a carbon chain planar to within 0.09 8 and a two-fold axis within 0.01 The B-and K-polymorphs have similar system of hydrogen bonds in different steric arrangements. The crystal structures of P-D-glucose and of cello- biose have been refined with new data.'40 The equatorial glycosidic C(l)-O(l) bonds are significantly short [1.383(4) and 1-397(4) 8 respectively] in agreement with observations in other sy~terns.'~' Methyl a-D-glucopyranoside is in the trans-C(1) chair-conformation. The C(1)-0( 1) bond 1.41 l(4) A is slightly shortened and there is a significant difference between C-0 bonds in the pyranose ring[C(1)-0(5) 1.414; 0(5)-C(5) 1.434(4) 8,].'" The absolute configuration of methyl-4,6-dichloro-4,6-dideoxy-a-~-glucopyranoside has been determined as (50);the molecule is in the normal chair-conf~rmation.'~~ Molecular Complexes.-In crystals of NNN'W-tetramethyl-p-diaminoben-zene iodide [tmpd] -t I-the cation has crystallographic 2/m ~yrnrnetry'~~ and in the bromide of the NN-dimethyl derivative [dmpd] 'Br- m ~yrnrnetry'~ is demanded for the cation.In both cations there is considerable quinonoid character as judged by the bond lengths. The 1:2 complex of tmpd with 7,7,8,8-tetracyanoquinodimethane[tcnq]; [tmpd] consists of columns of + tmq ions which overlap in characteristic fashion and are held together by hpd ions.The average spacing between tcnq ions is 3.24 Similarly in e 2 1 complex oftcnq with tetraphenylphosphonium ion [tpp]+[t~nq],,'~' dimer pairs of tcnq ions are found about an inversion centre sharing a single negative charge and overlapping in characteristic fashion. There is good agreement between the analyses on the geometry of the (tcnq))- ion and the distances are intermediate between these of (tcnq)" and (tcnq)-'. The mean perpendicular separation of the molecules in the 1 1 complex tcnq :anthracene is 3-50 A and in conjunction with the structural geometry implies only weak 136 F. D. Hunter and R. D. Rosenstein Acta Cryst. 1968,24 B 1652. 13' H. M. Berman and R. D. Rosenstein Acta Cryst.1968,24 B 435. 13* H. M. Berman G..A. Jeffrey and R. D. Rosenstein Acta Cryst. 1968,24 B 442. 139 H. S. Kim G. A. Jeffrey andR. D. Rosenstein Acta Cryst. 1968,24 B 1449. S. S. C. Chu and G. A. Jeffrey Acta Cryst. 1968,24 B 830. 141 S. S. C. Chu and G. A. Jeffrey Acta Cryst. 1967,23 1028. H. M. Berman and S. H. Kim Acta Cryst. 1968,24 B 897. 143 R. Hoge and J. Trotter J.Chem. SOC. (A) 1968,267. 144 J. L. de Boer A. Vos and K. Hume Acta Cryst. 1968,24 B 542. 14' J. Tanaka and N. Sakabe Acta Cryst. 1968,24 B 1345. 146 A. W. Hanson Acta Cryst. 1968,24 B 768. 14' P. Goldstein K. Seff and K. N. Trueblood Acta Cryst. 24 B 778. 60 George Ferguson charge-transfer interaction betwen molecules. The central six-membered rings of the two types of molecule are oriented at 30" to one another to ensure maximum 0ver1ap.l~~ Each molecule in the tmpd:chloranil complex lies in a mirror plane has symmetry 2/m and the short distance between the rings (b/2 = 3.284 A)indicates a strong intermolecular intera~ti0n.l~~ There is a mean separation of 3.32 A between the molecular planes in the pyrene :tetracyano-ethylene and some of the bond lengths in the pyrene molecule differ by 0.1 A from these found in the pyrene :tetramethyluric acid complex.' ' The structures of quinhydrone C6H402,C6H4(OH)2 and phenoquinone C6H,02,2C6H,0H have been refined.' 52 A striking example of virtually identical packing of molecules in a one-component crystal and in one of its addition compounds is provided by tetrabromoethylene and its 1 :1 pyrazine adduct.Similar but not identical behaviour is found in the tetraiodoethylene pyrazine system.' The 1:1 complex of 5-bromouridine and dimethylsul- phoxide (dmso) has hydrogen bonds between the DMSO oxygen and two hydroxyl-groups of the 5-bromouridine molecules. A comparison is made between the 5-bromouridine molecule in this structure and those found in two other related ~tructures.'~~ Natural Products.-The determination of the structure of a p-bromobenzoyl- urethane derivative of dihydrofomannosin establishes the structure of foman- nosin a biologically active metabolite of the fungus Fumes annosus. The deriva- tive (51) contains a puckered cyclobutane ring with a dihedral angle of 22" (158') and a cyclopentanone ring in an envelope conformation.' 55 Structure (52)has been determined for humulene bromohydrin; thus during its formation attack on the 1,2 double-bond in humulene is cis.The eight-membered ring has boat-chair conformation distorted from m symmetry by the ring fusion ; the mean C-C-C angle in the ring is 117-4(6)". The cyclobutane ring has a dihedral angle of 151" and the geometry of cyclobutane and cyclo-octane rings in a number of molecules is discussed.' 56 Caryophyllene 'iodonitrosite' a stable nitroxide radical has structure (36). The four-membered ring is buckled (dihedral angle 145") and the seven- and six-membered rings have chair conformations but with enlarged C-C-C angles because of intramolecular overcrowding effects.lo9 Structure (53) has been assigned to the 2-bromo- derivative of lumisantonin a photo-irradiation product of a-santonin.The configuration at the asymmetric carbon atoms confirms the now accepted stereochemistry of cc-santonin.' 57 148 R. M. Williams and S. C. Wallwork. Acta Cryst.. 1968. 24. B. 168. 149 J. L. de Boer and A. Vos Acta Cryst. 1968,24 B 720. 150 I. Ikemoto and H. Kuroda Acta Cryst. 1968,24 B 383. 15' A. Damiani P. de Santis E. Giglio A. M. Liquori R. Puliti and A. Ripamonti Acta Cryst. 1965,19 340. 152 T. Sakurai Acta Cryst. 1968,24 B 403. 153 T. D. Ah1 and 0.Hassel Acta Chem. Scad. 1968,22 715. 154 J. Iball C. H. Morgan and H. R Wilson Proc. Roy. Soc. 1968 A 302 225. 155 A. T. McPhail and G. A. Sim J. Chem. Soc. (B) 1968,1104. F. H. Allen and D. Rogers J.Chern. SOC.(B),1968,1047. 15' C P Huber and K. J Watson. J Chem. Soc (CI. 1968. 2441. X-Ray Crystallography Isoeremolactone has structure (54). Some of the C--C bonds are longer than expected and are associated with a high degree of substitution at these atoms ;similarly the bond angles at these atoms also differ from tetrahedral."' Details of the crystal structures of P-bromopicrotoxinin'59 and phorbol bromo- furoate'6o have been reported and preliminary details of the structures of OAc 15' Y. L. Oh and E. N. Maslen Acta Cryst,24 B 883. ls9 B. Jersley E. J. Rayn-Jonsen and J. Danielsen Acta Cryst. 1968 1968,24 B,1156. I6O R. C. Pettersen G. I. Birnbaum G. Ferguson K. M. S.Islam and J. G. Sime,J. Chem. SOC.(B) 1968.980. 62 George Ferguson eunicellin a diterpenoid of the gorgonian Eunicella stricta16' and ryanodol from Ryania speciosa Vahl,' 62 have been published.The configuration at C(13) in labdanolic and eperuic acids has been established as (S) (Prelog's notation) by an analysis of a p-bromophenacyl ester of labdanolic acid.'63 A considerable number of crystallographic papers have dealt with steroid structures in the past year. One of the most discusses the geometry and conformation of ring D in a number of steroids and some empirical rules that may serve as a basis for discussion of ring D conformation are recognised. To a first approximation the nature of the C(17) or C(16) P-substituent (except keto) has no discernible influence and extreme deformations of rings A B and/or c do not affect ring D.(A quantitative description of the conformation of the A B and c rings in steroids was published earlier.'65) Full details of the crystal and molecular structures of the steroid derivatives 3P-acetoxy-17a- hydroxy-16~-brorno-5~t-pregnan-l1,20-dione,'~~2l-bromo-3P 17a-dihy- . dro~y-5a-pregnan-ll,20-dione,'~~and 12a-bromo-l lP-hydroxyprog-esterone'68 have been published and also of the 2 1 complex of testosterone and mercuric ~hloride,'~' 3~,6~-dimethoxy-5~,19-cycloandrostan-17-one N-acetyl-p-brosylhydrazone,' o 9a-bromo- 17 P-hydrox y-17a-methylandrost-4-ene-3,l l-dione,17 fusidic acid methyl ester 3-p-brornoben~oate,'~~ withaferin A acetate p-bromobenzoate (55),' 73 and 3-methoxy-5~,19-cyclo-5,l0-seco-androsta-l( 10),-2,4-trien-17P-y1 p-bromobenzoate (56) which has ring A in a tub conf~rmation.'~~ The unusual structure (57) results from the benzilic acid rearrangement of 3a,l7P-diacetoxy- 1 1 -hydroxy-12-oxo-5P-androst-9( 1 1)-ene ; severe steric compression results from the cis fusion of the three five-membered rings.'75 Preliminary details have been announced of the structures of 8,13- diaza-18-noroestrone methyl ether,'76 the principal aglycon of horse chestnut saponin (58),177 the p-bromobenzoate of 6-oxoleucotylin (59),'78 and hirun- digen and anhydrohirundigen two natural 15-0xasteroids.'~~ 16' 0.Kennard D.G. Watson L. Riva di Sanseverino B. Tursch R Bosmans and C. Djerassi Tetrahedron Letters 1968,2879. 16' S. N. Srivastava and M. Przybylska Canad.J. Chem. 1968,46 795. 163 K. Bjamer G. Ferguson and R. D. Melville Acta Cryst. 1968,24 B 855. 164 C. Altona H. J. Geise and C. Romers Tetrahedron 1968,24 13. H. J. Geise C. Altona and C. Romers Tetrahedron 1967,23 439. 166 J. M. Ohrt B. A. Haner A. Cooper and D. A. Norton Acta Cryst. 1968,24 B 312. 167 J. M. Ohrt A. Cooper G. Kartha and D. A. Norton Acta Cryst. 1968 24 B 824. A. Cooper and D. A. Norton Acta Cryst. 1968,24 B 811. A. Cooper E. M. Gopalakrishna and D. A. Norton Acta Cryst. 1968,24 B 935. 170 C. Tamura and G. A. Sim J. Chem. SOC.(B),1968 8. 17' A. Cooper C. T. Lu and D. A. Norton J. Chern. SOC. (B),1968 1228. 17' A. Cooper and D. C. Hodgkin Tetrahedron 1968,24,909. 173 A. T. McPhail and G. A. Sim J. Chem. SOC.(B),1968,962. H. Hope and A.T. Christensen Acta Cryst. 1968 24 B 375. 175 J. S. McKechnie and I. C. Paul J. Amer. Chem. Soc. 1968,90 2144. 176 J. H. Burckhalter H. N. Abramson J. G. MacConnell R J. Thill A. J. Olson J. C. Hanson and C. E. Nordman Chem. Comm. 1968 1274. "' W. Hoppe A. Gieren N. Brodherr R Tsechesche and G. Wulff Angew. Chem. 1968,80 563. T. Nakanishi T. Fujiwara and K. Tomita Tetrahedron Letters 1968,1491. 17' 0.Kennard J. K. Fawcett D. G. Watson K. A. Kerr K. Stockel,W. Stocklin and T. Reich-stein Tetrahedron Letters 1968 3799. X-Ray Crystallography Precise details of the molecular geometry of the alkaloid reserpine (60)have been reported.18' The structure was solved by a combination of the symbolic (60) addition procedure for non-centrosymmetric space groups,' 81 a recycling procedure,ls2 and use of the tangent formula.'83 The authors note that 'the facility with which the structure was obtained for this molecule possessing 44 atoms exclusive of hydrogens and without a heavy atom indicates that the limit of the method has not been reached' ! In reserpine the trimethoxybenzoxy- group is nearly perpendicular to the remainder of the molecule and steric effects prevent all three methoxy-groups being in or near the plane of the benzene ring.The indole group is planar and only C(7)and N(8) are out of the plane in the adjacent ring. The next two rings are in chair conformation. Atom N(8) is pyramidal with bond angles near 111". Structure (61) has been determined for the alkaloid haloxine. Although this is a natural product with asymmetric carbon atoms its hydrobromide crystallises in a centrosymmetric space group so that it must be racemic.The three six-membered rings are in chair conforma- tion.la4 The structure of acutumine (62) an alkaloid containing chlorine is I. L. Karle and J. Karle Acta Cryst. 1968 24 B 81. la' J. Karle and I. L. Karle Acta Cryst. 1966 21 849. J. Karle Acta Cryst. 1968,24 B 182. la3 J. Karle and H. Hauptman Acta Cryst. 1956,9 635. lB4B. Nilsson Acta Cryst. 1968 24. B 252. George Ferguson Me0 Me0 (61) OMe OMe HO 0 HO closely related to that of hasubanonine but has a spiran-type juncture of two five- membered rings. Ring A is planar but the other two five-membered rings are puckered and the six-membered ring is in the boat conformation.' The structure and absolute configuration of coclaurine have been determined as (63). The (+)-enantiomer has D-configuration and the chirality of the molecular structure is correlated with circular dichroism measurements.' 86 The ten-membered ring in bothprotopine(64;R' = R2 = CH2)187andcryptopine(64;R'= R2 = Me)188 is severely buckled with the nitrogen atom well buried within it and held very close to the carbonyl carbon atom C(14); N-sC(14) is only 2-57(1) A. The three C-N bonds and the N..-C(14) 'bond' across the ring are nearly tetrahedrally arranged around the nitrogen atom. Consequently in the formation of a deriva- tive with tetravalent nitrogen inversion at the nitrogen atom would be required unless the fourth bond formed was N-C( 14).Alkaloid derivatives which have been the subject of preliminary communications include sparteine N( 16)-oxide [ions of which are held in the crystal by a short symmetrical O...H*-O lS5 M. Nishikawa K. Kamiya M. Tomita Y. Okamato T. Kikuchi K. Osaki Y. Tomiie I. Nitta and K. Goto J. Chem SOC.(B) 1968,652. ls6 J. Fridrichsons and A. McL. Mathieson Tetrahedron 1968,24 5785. lS7 S. R Hall and F. R Ahmed Acta Cryst. 1968 24 B 337. ''* S. R. Hall and F. R. Ahmed Acta Cryst. 1968 24 B 346. X-Ray Crystallography hydrogen bond 2.479(8)A],' 89 daphmacrine,' coulteropine,' 9' kreysiginine and morphine,lg2 vallesamidine,' 93 capaurimine and capaurine,lg4 (-)-kopsanone,l 95 oxotuberostemonine,' 96 batrachotoxinin A a novel steroid alkaloid from the Colombian poison-arrow frog,' 97 and beratrobasine.' 98 Duclauxin one of the metabolites of PeniciIIium Duclauxi Delacroix has been established as (65; R = H) by an analysis of a monobromo-derivative (65; R = Br).It consists of two nearly planar rings one containing an iso- coumarin and the other a dihydroisocoumarin nucleus ;these are joined through the five-membered ring to form a hinge-like structure.lg9 The structure and absolute configuration of the fungus metabolite ophiobolin has been established as (66). The derivative used was the methoxybromide.200 This structure is closely related to those of ceroplasteric acid (67; R = C02H) and ceroplastol I (67; R = CH,*OH). whose structure have also been determined by X-ray methods.'* lS9 S.N. Srivastava and M. Przybylska Tetrahedron Letters 1968 2697. T. Nakano Y. Saeki C. S. Gibbons and J. Trotter Chem. Comm. 1968,600. 19' F. R Stermitz R M. Coomes and D. R. Harris Tetrahedron Letters 1968. 3915. 19' J. Fridrichsons M. F. Mackay and A. McL. Mathieson Tetrahedron Letters 1968 2887. 193 S. H. Brown C. Djerassi and P. G. Simpson J. Amer. Chem. SOC.,1968,90 2445. 194 T. Kametani M. Ihara K. Fukumoto H. Yagi H. Shimanouchi and Y. Sasada Tetrahedron Letters 1968 4251. 19' B. M. Craven B. Gilbert and L. A. P. Leme Chem. Comm. 1968,955. 196 C. P. Huber S. R Hall and E. N. Maslen Tetrahedron Letters 1968,4081. 19' T. Tokuyama J. Daly B. Witkop I. L. Karle and J. Karle J. Amer. Chem. SOC. 1968 90 1917. 19* G. N. Reeke jun.R L. Vincent and W. N. Lipscomb J. Amer. Chem. SOC. 1968,90 1663. 199 Y. Ogihara Y.Iitaka and S. Shibata Acta Cryst. 1968,24 B 1037. 'O0 M. Morisaki S. Nozoe and Y. Iitaka Acta Cryst. 1968 24 B 1293. 201 Y. Iitaka I. Watanabe I. T. Harrison and S. Harrison J. Amer. Chem. Soc. 1968,90 1092. George Ferguson Vanadyl deoxophylloerythroetioporphyrin,C,,H 34N4V0,(68),an analogue of chlorophyll has the shape of a very shallow saucer. The four nitrogens are coplanar with the vanadium atom 0-48A from this plane. The strain introduced by ring E is not localised but transmitted throughout the molecule :the four-fold symmetry characteristic of many porphyrins and porphines has vanished. Another effect of the E ring is that it appears to have ‘pushed’ the nitrogen atom of ring c in towards the vanadium as the V-N distance (1.97 A) is significantly shorter than the other three V-N distances (mean 2-11 A$).2o2 ’O’ R C.Pettersen and L. E. Alexander J. Amer. Chem SOC.,1968,90 3873.

ISSN:0069-3030    

DOI:10.1039/OC9686500041

出版商:RSC    

年代:1968

数据来源: RSC

摘要:

3 (Part i) REACTION MECHANISMS By J. G. TiUett (Chemistrv Department Universitv of Essex Colchester) This year an extensive coverage of acid-base catalysis is included since this has not been fully reported recently. Similarly since deuterium isotope effects were dealt with comprehensively last year this topic is covered only briefly on this occasion. Acidity Functions and Molecular Basicity.-New acidity-function data reported this year includes values of H for HClO in aqueous 2-butoxyethanol,' H for aqueous H2S0,,2 and HR for constant ionic-strength solutions of HC104 in aqueous di~xan.~ Good agreement between calculated and experi- mental values of H for iodic acid have been obtained4 by using Wyatt's proton hydration model.' H-Scales for aqueous alkali hydroxides have come under criticism.6 The observed trend in basicity for solutions of equal concentration H-(LiOH) < H-(NaOH) < H-(KOH)is thought to be only apparent when due allowance is made for ion-pair formation,6 attention being drawn to the danger of correlating reaction rates with uncorrected H-values.The protonation in acetonitrile of water alcohols and diethyl ether has been ~tudied.~ The protonation of a number of aromatic and a,P-unsaturated aldehydes ketones and carboxylic acids in sulphuric acid has been shown to follow the HA acidity function rather than H,.8 The basicity of some sulphoxides in aqueous sulphuric acid has been determined by measurements of chemical shifts.' An n.m.r. study of the protonation equilibria of carbamic acid esters reveals similar protonation behaviour to that of amides and in- dicates pK values intermediate between structurally similar amides and esters.lo A detailed study of the protonation of azulene-1-carboxylic acid over a wide pH range has eliminated some of the previous inconsistencies." At low pH it decarboxylates slowly.Above 5.0-~acid however the conjugate acid (I) is formed ' J. G. Tillett and R. C. Young J. Chem. SOC. (B) 1968,209. ' P. Vetesinki J. Bielavsky and M. Vecera Coll. Czech. Chem. Comm. 1968,33 1687. H. Nicholson and P. A. Wyatt J. Chem. SOC. (B) 1968 198. 'J. G. Dawber J. Chem. SOC.(A),1968,1532. ' M. Oyeda and P. A. H. Wyatt J. Phys. Chem. 1964,68,1857. J. R. Jones Chem. Comm. 1968,513. ' I. M. Kolthoff and M.K. Chantooni J. Amer. Chem. SOC. 1968,90 3320. * R. I. Zalewski and G. E. Dunn Canad. J. Chem. 1968,46,2469. P. Haake and R. D. Cook Tetrahedron Letters 1968 427. lo V. C. Armstrong and R. B. Moodie J. Chem. SOC. (B) 1968,275. 'I J. L. Langridge and F. A. Long. J Anier. Cheni. Snc.. 1968.90. 3088. J. G. Tillett HH The slope of the indicator plot (1.1) is similar to that expected for a Hammett base rather than a carbon acid. This is attributed to extensive solvation of (I) compared to the conjugate acid of azulene itself. A study of several acid-base equilibria involving hydrocarbons in Me,SO shows that rates of proton exchange are greater in Me,SO than in methanol for reactions with the same equilibrium constant in both solvents.'2 Acid-Base Catalysis.-Carboxylic Esters Ethers Acetals and Related Compounds.The realisation that the Zucker-Hammett hypothesis can no longer be regarded as a reliable criterion of mechanism has led to a search for other criteria. Bunton and his co-workers have suggested13 that the effect of added electrolytes can be used for this purpose and have pointed out that for A-1 reactions the catalytic effects of added acids decreases in the sequence HC104 > HCl -H,SO, whereas for typical A-2 reactions the relative order is H,S04 > HCl -HBr > HClO,. Thus the hydrolyses of methyl 2,4,6-trimethylbenzoate t-butyl acetate and t-butyl benzoate show the former sequence whilst the hydrolyses of methyl benzoate and ethyl acetate show the latter order.Anions with low charge-density seem to preferentially stabilise transition-states with carbonium-ion character whereas the opposite is true for A-2 reactions where there is considerable hydrogen bonding between the solvent and transition state. Studies of the acid-catalysed hydrolyses of methyl pseudo-2-benzoyl- ben~oate,'~ a-methylallyl acetate,I5 1-arylcyclopropyl acetates,I6 t-butyl acetate," vinyl esters,18 nitroalkanes," amides,,' carbamates,,' and ureas2' have all been reported. The mechanism of hydrolysis of ethyl carbamate changes from A-2 to A-1 with increasing acidity.,' Further kinetic studies of the hydrolyses of ethyl vinyl ether have been reported.21,22 The effect of substituents on the rate of the acid-catalysed C. D. Ritchie and R.E. Unchold J. Amer. Chem. SOC. 1968,90 3415. l3 C. A. Bunton J. H. Crabtree and L. Robinson J. Amer. Chem. SOC. 1968,90 1258. l4 D.P.Weeks A. Grodski and R. Fanucci J. Amer. Chem. SOC. 1968,90,4958. l5 R.A.Fredlen and I. Lauder Austral. J. Chem. 1968,21,1727. l6 J. A. Landgrebe and W. L. Bosche J. Org. Chem. 1968,33 1460. l7 H.Sadek and F. Y. Khalil Z. phys. Chem. (Frankfurt),1968,57 306. L.F. Kulish and 0.I. Kovol Ukrain.khim. Zhur. 1968,34,495. l9 R.B. Cundall and A. W. Locke J. Chem. SOC.(B),1968,98. 'O V.C. Armstrong D. W. Farlow and R. B. Moodie J. Chem. SOC.(B),1968 1099. M. M. Kreevoy and R. Elliason J. Phys. Chem. 1968,72,1313. '' A. J. Kresge and Y. Chiang J. Amer. Chem. SOC..1968.90.5309. Reaction Mechanisms 69 hydrolysis of phenyl vinyl ether is compatible with rate-determining protona- tion at the P-carbon atom.23 (Scheme 1).Hi0 + CH,=CH*OAr CH,-CH*OAr H20 CH,*CHO + HOAr SCHEME 1 The acid-catalysed hydrolysis of ethyl vinyl ether in dimethyl sulphoxide is also controlled by a rate-determining proton transfer to carbon.24 The rate has been divided into components arising from the dimethyl sulphoxide-solvated proton and the monohydrated proton the former being about twice as large as the latter. This shows that direct proton transfer from strong acid to a carbon atom is possible without an intervening water molecule. It is suggested that this mechanism predominates even when water is the solvent. Thus n = 0 in the generalised scheme for proton transfer from an aqueous acid to an organic substrate (S) (Scheme 2).I p-8 . 0- I SCHEME 2 A similar inference has been drawn for the protonation of nitro-alkane anions.” Kinetic studies of the acid-catalysed hydration of phenylacetylene,26 phenylbenzoylacetylene’’~ and 1-phenylpropyne2’ have been reported. The rate of hydration correlates with H, is very sensitive to substituents in the ring and exhibits an inverse kinetic deuterium-isotope effect [k(H,O)/ k(D,O) -21. This is attributed to rate-determining proton transfer which leads to the formation of a vinylic carbonium ion. The acid-catalysed isomerisa- tion of stilbene is also thought to proceed by way of a rate-determining proton transfer.30 The acid-catalysed dehydration of 1,2-diarlyethanols3 32 involves ‘9 reversible formation of a 1,2diarylethyl cation followed by rate-determining proton loss to give trans-stilbene.23 T. Fueno I. Matsumura J. 0.Kuyama and J. Furukawa Bull. Chem. Soc. Japan 1968,41,818. 24 M. M. Kreevoy and J. M. Williams J. Amer. Chem. SOC. 1968,90 6809. 25 D. M. Goodall and F. A. Long J. Amer. Chem. SOC. 1968,90,238. 26 D. S. Noyce and M. D. Schiavilli J. Amer. Chem. SOC.,1968,90,1023. 27 D. S. Noyce and M. D. Schiavilli J. Amer. Chem. SOC. 1968,90 1020. 28 D. S. Noyce and K. E. De Bruin J. Arner. Chern. SOC.,1968,90,372. 29 D. S. Noyce and M. D. Schiavilli J. Org. Chem. 1968,33 845. ’O D. S. Noyce D. R. Hartter and F. B. Miles J. Amer. Chem. SOC.,1968,90,4633. D. S. Noyce D. R. Hartter and R. M. Pollack J. Amer. Chem.SOC.,1968,90 3791. 32 D. S. Noyce. D. R.Hartter. and F. B. Miles. J. Amer. Chem. SOC..1968.90.3794. 70 J. G. Tillett The hydrolyses of l-cyano-2,2-dimethoxyethylene(2) and 2-dichloro-methylene-1,3-dioxalan (3) are both subject to general acid catalysis. 33 CH2-Y NC\ PMe I C=Cl* HF=YOMe CH,-d (2) (3) HlO Has a lower catalytic-constant than predicted from the Brsnsted plot for weaker acids. At high concentrations of carboxylic acid buffers there is a fall-off in the rate of hydrolysis which was attributed to dimerisation of the undissociated acids or association between carboxylic acid and carboxylate anion. For compound (3) the hydrogen atom added in the formation of 2- hydroxyethyl dichloroacetate does not exchange with the solvent so that the product isotope effect could be determined.Taken in conjunction with the isotopic-rate ratio this permitted an evaluation of the transfer contribution to the solvent isotope effect. A systematic study of the effect of leaving group on the mechanism of acetal hydrolysis have been reported.34 The p-value for a series of 2-(para-substituted phen0xy)tetrahydropyrans is -0.92.The deuterium solvent effect decreases with increasing electron-withdrawal in the leaving group. The value of k(D,O)/ k(H,O) = 2-82 found for 2ethoxytetrahydropyran is in the range usually associated with an A-1 mechanism and is in agreement with values for other simple acetals. The solvent isotope effect however For 2+-nitrophenoxy)- tetrahydropyran of 1.33 indicates some solvent participation in the rate- determining step.A mechanism involving partial rate-determining protonation of oxygen (4) is consistent with this view. (4) The values of ASS (+7.9 e.u and -7-6 e.u respectively) provide further confirmation of this change. The extent of proton transfer decreases along the series as electron-withdrawal increases. As might be expected general acid catalysis by formate buffers was observed for the hydrolysis of 2+-nitro- phenoxy)- and 2-(p-~hlorophenoxy)-tetrahydropyran. The hydrolyses of tetramethylene glycol acetals proceed much more slowly 33 V. Gold and D. C. A. Waterman J. Chem. SOC. (B),1968,839,849 34 T. H. Fife and L. K. Jao J. Amer. Chem. Soc. 1968.90.4081. Reaction Mechanisms 71 in comparison with other types of acetals.”’ The AS value for the hydrolysis of 4,4,5,5,-tetramethyl-2-(p-nitrophenyl)-l,3dioxolanein aqueous HCl is -15.8 e.u.This suggests that the presence of methyl substituents in the 1,3- dioxolane ring inhibits the normal A-1 reaction and that attack by a solvent molecule (5)is the ratedetermining step. The AS$ value however of 2,4,4,5,5,-pentamethyl-2-phenyl-1,3-dioxalaneis similar to that observed for ethylene glycol acetals and ketals and it is likely that the transition state for hydrolysis of ths compound may have considerably more unimolecular character than the tetramethylene glycol acetals unsubstituted at the acetal carbon. The kinetics of hydrolysis of 2-alkoxytetrahydrofurans and pyrans have also been reported by other workers.36 The hydrolysis of 3,4-O-benzylidenelincomycin acetal is thought to proceed through the usual A-1 pathway in spite of an atypical ASf value (-13.6 e.u.) which is attributed to the unusual structure of this particular a~etal.~~ Con-formational effects in the hydrolysis of other cyclic acetals have also been in~estigated.~~ A kinetic study of the hydrolysis of the tetramethyl acetal of p-benzoquinone showed surprisingly that the diacetal (6) is about an order of magnitude less reactive than 2,2-dimethoxypropane. 39 Me0 OMe 0 A kinetic study of the acid-catalysed hydrolysis of some indolyl-P-D-gluco- pyranosides has been rep~rted.~’ The kinetic deuterium isotope effect indicates a rapid pre-equilibrium protonation and application of the Zucker-Hammett and Bunnett criteria suggests an A-1 mechanism for hydrolysis.Values of AS* in the range 0.4to 2.2 were obtained. The possibility of an ‘open-chain’ mechanism still cannot be definitely excluded. Studies of the acid-catalysed hydrolyses of a variety of other glycosides have also been reported.4145 The pH-rate profiles for the hydrolyses of both o-carboxyphenyl-P-D- glucopyranoside and o-carboxyphenyl-2-acetamido-2-deoxy-~-~-glucopyrano-35 T. H. Fife and L. H. Brod J. Org. Cheni. 1968,33 4136. 36 A. Kankaanpera and K. Mukki Suomen Kem. 1968,41 B 42. 37 M. J. Taraszka and W. Morozowich J. Org. Chem. 1968,33,2349. 38 P. Watts J. Chem. SOC.(B),1968 543. 39 R. K. Chatwoerdi J. Adams and E. H. Cordes J. Org. Chem. 1968,33 1652.40 J. P. Horwitz C. V. Easwaren and L. S. Kowaleszyk J. Org. Chem. 1968,33 3174. 41 J. Szeytli Acta. Chim. Acad. Sci.Hung. 1968,56 175. 42 M. D. Saunders and T. E. Timell Carbohydrate Res. 1968,6 12 121. 43 C. K. De Bruyne and F. Van Vitnendaele Carbohydrate Res. 1968,6 367. 44 N. Roy and T. E. Timell. Carhohrdrate Res.. 1968. 6.475 7. 17. ‘’ D. Piszkiawicz and T. C. Bruice. J. Anier. Chem. Soc.. 1968. 90.2156. J G. Tillett side show a plateau rate followed by a decreasing slope of ca. -10 above pH 4.46 The plateau and descending rate are ascribed to intramolecular carboxy-group participation rather than specific hydrogen-ion catalysis of the glycoside carboxylate anion. The additional rate enhancement found for the acetamido-deoxypyranoside is attributed to concerted intramolecular carboxy-group general acid catalysis and intramolecular acetamido-group nucleophilic catalysis (Scheme 3).I Me products I Me SCHEME3 Intramolecular nucleophilic attack by the neutral acetamido-group was considered to be more likely than intramolecular nucleophilic attack of the ionized acetamide group on the protonated glycoside site. By analogy it was suggested that spontaneous hydrolysis of o-carboxyphenyl-P-D-gluco-pyranoside involves intramolecular carboxy-group general acid catalysis (7). 0 There was no evidence of intramolecular acetamido-participation in the specific hydrogen-ion-catalysed hydrolysis of 2-acetamido-2-deoxy-~-~-g~uco-pyranosides. Specific hydrogen-ion catalysis has also been observed in the hydrolyses of methyl and pyranosyl glycosides of glucose and N-acetyl- glucosamine.46 When log k,+ values for P-D-glycosides of N-acetylghcosamine are plotted against the k + values for the corresponding P-D-glucopuranosides a linear relationship is obtained.The point corresponding to the methyl glycosides however deviates significantly from the line and corresponds to a 50-fold rate enhancement over that expected. This is attributed to intra- 46 D. Piszkiewicz and T. C. Bruice J. Amer. Chem. SOC.,1968,W.5844. Reaction Mechanisms 73 molecular nucleophilic displacement by the 2-acetamido-group at the proto- nated glycoside bond (Scheme 4). bJOMe HN OHMe I c =o c EO I I Me Me 1 H2O fast b HN / o + *C C=O I I Me Me SCHEME 4 Intramolecular acetamido-participation in the specific acid-catalysed hydrolyses of methyl-P-N-acetylglucosamineis considered to compete favourably with the normal path through an oxocarbonium ion intermediate because the small methyl aglycone does not inhibit the formation of the trans-diaxial conformation most favourable to acetamido-participation.Several other investigations of neighbouring carboxyl-group participation have been reported. The reactions of acetylsalicylic acid and some related phenyl esters with the weak bases nicotinamide semicarbazide and methoxy- amine occur predominantly with the acidic uncharged species of acetyl- salicylic acid and show rate accelerations which are ascribed to intramolecular general acid catalysis (8).47 Rate enhancement of similar magnitude for the reaction of the acetylsalicylate anion with e.g.semicarbazide are attributed to general-base catalysis by the o-carboxylate anion (9). The formation of an anhydride intermediate by intramolecular nucleophilic attack of the carboxylate group on the ester function was discounted. RNH "\ /Me oo-c*3 ' c11-u OIH 0 (8) (9) 47 T. St. Pierre and W. P. Jencks J. Amer. Chem. SOC. 1968,90 3817. 74 J. G. Tillett Bruice and Bradb~ry~~ have studied the related hydrolysis of the p-bromo- phenyl esters of glutaric acid. The rate acceleration caused by 3,3disubstitution in this reaction which is thought to proceed by way of intramolecular nucleo- philic catalysis (Scheme 5)with the formation of a cyclic anhydride intermediate is due almost entirely to a more favourable AS term.R' CH,-CO,H R' CH2-CO; \/ \/ R1 CH,.CO,H \/ c-k 'CH,. C02H SCHEME 5 By comparison with the previous example this suggests the possibility of a change in mechanism from intramolecular nucleophilic attack for those substrates where a cyclic anhydride can be formed to intramolecular general- base assisted attack of water when a cyclic anhydride cannot be formed. Gold and his co-worker~,~~ were able to distinguish between these two mechanisms in the acetate-catalysed hydrolyses of aryl acetates by trapping the acetic anhydride intermediate by reaction with added aniline. The choice between general-base catalysis and intramolecular nucleophilic displacement depends significantly on the relative basicities of the nucleophile and the leaving group.Thus acetate does not catalyse the hydrolysis of substituted phenyl acetates if the leaving group is more than 3-4 pK units more basic than the catalyst5' In the case of acetylsalicylic acid the leaving group is at least 6-7 pK units more basic than the carboxylate group. Incorporation of two nitro-groups ortho and para to the phenolic oxygen should reduce its basicity markedl~.~' Oxygen-18 is incorporated into the 3,5-dinitrosalicylic acid formed on hydrolysis of acetyl-3,5-dinitrosalicylate in an enriched solvent This evidence and the kinetic data is consistent with a mechanism (Scheme 6)involving intramolecular displacement by carboxylate ion with the formation of a mixed salicylic acetic anhydride intermediate.T. C. Bruice and W. C. Bradbury J. Amer. Chem. SOC.,1968,90 3808. 49 V. Gold D. G. Oakenfull and T. Riley J. Chem. SOC.(B) 1968,515. 50 D.G. Oakenfull T. Riley and V. Gold Chem. Comm. 1966,385. 51 A. R.Fersht and A. J. Kirby J. Amer. Chem. SOC. 1968.90. 5818. Reuction Mechanisms 16 J. G. Tillett The slow step is the decomposition of the anhydride intermediate although this is itself subject to intramolecular general-base catalysis. Intermolecular reactions with oxyanion nucleophiles however involve uncatalysed nucleophilic attack on the ester. The hydrolysis of acetyl-3,5-dinitrosalicylicacid is faster than its anion.52 Solvolysis in 50 ”/ aqueous methanol produces significant quantities of methyl 3,5-dinitrosalicylate indicating that intramolecular catalysis and anhydride formation is involved in this case also.Nucleophilic catalysis seems to be favoured for the hydrolysis of acetylsalicylic acids because of a more favourable equilibrium-constant for the formation of the protonated form rather than the anion of the mixed anhydride intermediate. A further striking example of this principle is found when a second carboxy- group is introduced into the 6-position of acetylsalicylic acid.’ This accelerates the rate of hydrolysis by a factor of ca. 6000. This acceleration is attributed to ‘series’ nucleophilic catalysis in which the acetyl group is first transferred to the adjacent carboxy-group and then displaced from it by the second carboxy- group (Scheme 7).CO-H O=y’ -\-,!J OH v ‘OH SCHEME 7 The acetate ion-catalysed methanolysis of p-nitrophenyl acetate also involves an acetic anhydride intermediate.54 The hydrolysis of 4-(2-acetoxyphenyl)imidazolealso proceeds by way of a general-base mechanism (10)rather than by nucleophilic catalysis. This is in accord with the fact that th.= imidazoyl nitrogen atom is a poorer nucleophile (pK,, 5-5)in this compound than in imidazole (pK,, 7.0). Solvolysis under alkaline conditions of 4(5)-(2-amino-3-bromopropyl)-imidazole forms the aziridine (1 1) 52 A. R. Fersht and A. J. Kirby J. Amer. Chem. SOC. 1968,90 5826. 53 A. R. Fersht and A. J. Kirby J. Amer.Chem. SOC.,1968,90 5833. 54 R. L. Schowen and C. G. Bohm J. Amer. Chem. SOC.,1968,90,5835. 55 S. M. Felton and T. C. Bruice Chem. Comm. 1968 907. 5h D. A. Usher. J. Amer. Chem. SOC..1968.90. 363. Reaction Mechanisms Me H II Simple displacement of bromide can however be effected by external nucleo- philes after chelation with copper (11) ions (12).57A complex pH-rate dependence involving three imidazole-dependent terms is obtained for the hydrolysis of y-methyl- 1,-chloro- and p-nitro-benzoylimidazole in H,O -imidazole buffer solutions. The imidazole-catalysed hydrolysis of N-acetylserinamide is only moderately affected by steric effects in the catalysing base.59 This is consistent with classical base catalysis (13) since nucleophilic catalysis would be strongly retarded by large groups in the 2-position.Oh-NHAc I! I Me C-O.CH,CH.C .NH 1 I I II 0 /Ox*. HH Aminolysis and Related Reactions. Evidence continues to accumulate for the existence of tetrahedral intermediates in the hydrolysis of both cyclic and acylic irnidates6’ The hydrolysis of ethyl N-phenylacetimidate and methyl (+)-N-(a-methylphenylethy1)acetimidate yields amines and esters in acid solution and amides at alkaline pH. At constant pH bifunctional catalysis diverts the breakdown of tetrahedral intermediates from the formation of amides to the explusion of amines.61 The kinetics of hydrolysis of 2,2,2-5’ D. A. Usher J. Amer. Chem. Soc. 1968,90,367. ’13 J. P. Klinman and E. R. Thornton J. Amer.Chem. SOC.,1968,90,4390. 59 J. B.Milstien and T. H. Fife J. Amer. Chem. SOC.,1968,90,2164. 6o G.L. Schmir J. Amer. Chem. SOC. 1968,90,3478. R.K. Chaturvedi and G. L. Schmir. J. Amer. Chem. Soc.. 1968.90.4413. 78 J. G. Tillett trifluoroethyl- 2-methoxyethyl- and ethyl N-methylacetimidate are also consistent with the formation of a tetrahedral intermediate.62 The aminolysis of methyl formate by amines in aqueous solution proceeds predominantly by general base catalysed attack of free amine at high pH.63 The rate-determining step for the reaction of morpholine with methyl formate changes from being the formation of the addition intermediate at high pH to its decomposition at low pH. A comprehensive investigation of the sensitivity of aminolysis reactions to the basicity of amines for a series of acetate esters has been reported.64 The kinetics of the reactions of trifluoroacetanilide with hydroxylamine and hydrazine have been studied.65 The first direct observation of a tetrahedral intermediate in amidine hydrolysis has recently been reported.66 Spectroscopic and kinetic evidence were obtained for the existence of both forms (14 and 15) of the intermediate in the hydrolysis of diphenylimidazolium chloride. n PhNONPh PhN NPh v HXOH U CHO Diazo-compounds. Zwanenburg and his co-workers have reported a further study of the acid-catalysed hydrolysis of aryl- and alkyl-sulphonyldiazo- rnethane~.~~ The reactions shows specific hydrogen-ion catalysis as indicated by the kinetic solvent-isotope effect.Fast H-D exchange of the methine proton observed by n.m.r. spectroscopy shows that carbon protonation occurs as the first step. The effectiveness of added acids is in the order HBr > HC1 > HC104. This different catalytic efficiency is attributed to specific anion or nucleophilic catalysis by the anion of the acid in which anions possessing nucleophilic properties compete with the solvent for the conjugate acid thereby providing an alternative route to that followed in the absence of such nucleophiles (Scheme 8). In perchloric acid containing added chloride ions the rate enhancement as compared with solutions containing the same concentration of added perchlorate could be directly correlated to the amount of chloro-product formed.Such a correlation implies that the water reaction also proceeds by an A-2 mechanism since in an A-1 process with water and 62 T. C. Pletcher S. Kochler and E. H. Cordes J. Amer. Chem. SOC. 1968,90 7072. 63 G. M. Blackburn and W. P. Jencks J. Amer. Chem. SOC. 1968,90,2638. 64 W. P. Jencks and M. Gilchrist J. Amer. Chem. Soc. 1968,90,2622. 65 S. 0.Eriksson Acta Chem. Scad. 1968,22,892. 66 D. R. Robinson Tetrahedron Letters 1968 5007. 67 J. B. F. N. Engbeits and B. Zwanenburg Tetrahedron 1968.24. 1737. Reaction Mechanisms 79 halide ions competing for a carbonium ion additional chloro-product would be formed. + + Ar,SO,CHN + H,O + ArS0,*CH2N2+ H20 + +H,O ArSO,*CH,N ArSO,CH,OH sly' Ar SO,CH,X (X = Br or C1) SCHEME 8 The hydrolysis of ethyl diazoacetate also shows specifichalide-ion catalysis.6 The rate enhancement by halide ions correlates with the amount of halo-genoacetate produced suggesting a similar mechanism of hydrolysis to that postulated for the diazosulphones halide ions again competing with water for the conjugate acid of the substrate in the rate-determining step.A re-investigation of the acid-catalysed hydrolysis of dia~o-ketones~~ suggests that the earlier assignment7' of an A-1 mechanism to this reaction is incorrect. The earlier conclusion was based mainly on an analysis of the kinetic data in terms of the Zucker-Hammett criterion and on entropy of activation data. It has been shown recently,67however that the acidity criterion is not valid for the analogous diazo-sulphone system and this must throw doubt on its use in this case.Evidence has now been presented which shows that for the acid-catalysed hydrolyses of diazo-ketones both the water and halide-ion reactions proceed by an A-2 mechanism.69 The diazo-ketones -sulphones and -esters all hydrolyse therefore by the same mechanism. Several other kinetic studies of diazo-compounds have also been reported. 71-74 Other reactions reported to exhibit nucleophilic catalysis are the acid-catalysed hydrolyses of ethylene sulphoxide7 and 3-phenylsydnone.76 Other Reactions. Kice and his co-workers have published further details of their studies on the reactions of the sulphur-sulphur bond.77Both electro-philic and nucleophilic catalysis either individually or concomitantly can be observed in these systems.Thus the kinetic equation of the halide-and acetate-ion catalysed hydrolysis of sulphinyl sulphones is of the f~rm,~~,~' kobs - kxo[X-] + k,,[X-] [H']. The first term represents solely nucleophilic '' W. J. Albery J. C. E. Hutchins. R. M. Hyde. and R. H. Johnson J. Chenz. Soc. (B),1968 219. 69 S. Aziz and J. G. Tillett Tetrahedron Letters 1968 2321 ;J. Chem. Soc. (B) 1968 1302. 70 H. Dahn and H. Gold Helu. Chim. Actn. 1963,46 983. W. Jugelt and D. Schmidt Tetrahedron 1968,24,59. 72 A. J. Harget K. I). Warren and J. R. Yandle J. Chem. Soc. (B),1968,214. l3 W. Jugelt and L. Berseck Tetrahedron Letters 1968 2659 2665. 74 D. Bethel1 and R. D. Howard J. Chem. Soc. (B),1968,430. 75 G. E. Manser.A. D. Mesure and J. G. Tillett Tetrahedron Letters 1968 3153. 76 S. Aziz A. F. Cockerill and J. G. Tillett Tetrahedron Letters 1968,5479. 7' J. L. Kice Accounts Chem. Res. 1968 1 58. '' J. L. Kice and G. Guaraldi J. Org. Chem. 1968,33 793. 79 J. L. Kice and G. Guaraldi. J. Amer. Cheni. Snc.. 1968.90.4076. 80 J. G.TiIlett catalysis (Scheme 9) whereas the second term involves both electrophilic and nucleophilic assistance (Scheme 10). 0 II X-+ Ar-S-S-Ar ArS-X + Ar*SO II II 00 products (X = C1 Ar = p-MeC,H,) SCHEME 9 0 II kxl X-+ ArS-SAr + H,O ArS-X + ArS0,H + H,O II II "I1 I 00 1 H,O fast products SCHEME 10 The kinetics of the acid-catalysed thiolsulphinate-sulphide reaction have also been investigated.8o The mechanisms of the halide-ion and acid-catalysed racemisation of phenyl benzylthiosulphinate,81 rn-chlorophenyl methyl sul- phoxide,82 and 3-benzylsulphinylbutyricacid83 have also been investigated. The hydrolysis of ethyl thioacetate is catalysed by cyanide ion and by hydrogen cyanide whereas the hydrolysis of ethyl benzoate and ethyl p-nitrobenzoate are not. 84 The kinetic form of the rate equation for the hydrolysis of ethyl thiolacetate in cyanide buffers is k, = ko,-[OH-] 4-kCN-[CN-] + k,m[HCN] The second term represents nucleophilic catalysis by cyanide ion (Scheme 1l) the deuterium solvent effect (k -)Hzo/(k -)D20 -1.25precluding general-base catalysis. slow CN-+ MeCOOSEt -MeCO-CN + EtS-fast MeCO-CN + H20 -MeC0,H + HCN SCHEME 11 8o J.L. Kice and G. B. Large J. Org.Chem. 1968,33 1940. 81 J. L. Kice and G. B. Large J. Amer. Chem. Soc. 1968,90,4069. " D. Landini F. Montanari G. Modena and G. Scorrano Chem. Comm. 1968 86. 83 S. Allenmark and C-E. Hayberg Acta Chem. Scund. 1968,22,1694. 84 F. Hibbert and D. P. N. Satchell. J. Chem. Soc. (B). 1968. 565. 568. Reaction Mechanisms The hydrogen cyanide catalysis represents an unusual acid-catalysed nucleo- philic catalysis of ester hydrolysis for which a number of possible mechanisms may be envisaged. The kinetics of the addition of carboxylic acids to dimethyl- keten in ether and to diphenyl- -and mesitylphenyl-keten in o-dichlorobenzene are consistent with two alternative rnechanism~.~~ In ether solution the addition of weak carboxylic acids involves a cyclic transition-state (16) with nucleophilic attack by the acid on the carboxy-carbon of the keten R’,CX=O R’ 25=C 7 -R’,CH .C02.COR2 + R’CO~H -H\a&? \R2 The preferred mechanism for stronger carboxylic acids is thought to involve carbon protonation (Scheme 12). R;C==C=O + R2*C02H-[RiCH-CH=O]+ [R2C02]-I R~H-co 00 COR~ SCHEME12 The kinetics of the addition of water and alcohols to dimethylketen have also been measured.86 Both the spontaneous and acid-catalysed addition of nucleophiles proceed by way of cyclic transition states analogous to that discussed above. The addition of hydrogen chloride to dimethylketene involves carbonyl addition followed by a prototropic rearrangement.”Further studies of bifunctional catalysis on the mutarotation of glucoseg8* 89 and in esterolytic reaction^,'^ have been reported. The catalytic effect of micelles on the hydrolyses of ester.^^'-^^ and on the addition of cyanide ion to N-substituted 3-carbonyl- pyridinium ions9’ have also been reported. Esters of Inorganic Oxy-acids.-( a) Phosphorus ucids. Bun ton has reviewed ‘’ J. M. Broidy P. J. Lillford and D. P. N. Satchell J. Chem. SOC.(B),1968 885. 86 P. J. Lillford and D. P. N. Satchell J. Chem. SOC.(B) 1968 889. 87 P. J. Lillford and D. P. N. Satchell J. Chem. SOC.(B) 1968 897. 88 A. Kerzomard and M. Renard Tetrahedron Letters 1968 769. 89 P. R. Rony J. Amer. Chem. SOC. 1968,90,2824. R. F. Pratt and J. M. Lawler Chem. Comm.1968,522. L. R. Romstead and E. H. Cordes J. Amer. Chem. Soc. 1968,90,4404. 92 T. C. Bruice J. Katzhemtler and L. R. Fedor J. Amer. Chem. SOC. 1968,90 1333. 93 R. B. Dunlop and E. H. Cordes J. Amer. Chem. SOC.,1968,90,4395. 94 C. Gitier and A. Ochoa-Solama J. Amer. Chem. SOC. 1968,90 5004. 9s R. N. Lindquist and E. H. Cordes. J. .4nirv. Chem. Soc.. 1968.90. 1269. 82 J. G.Tillett the mechanisms of hydrolysis of mono-alkyl and aryl derivatives of ortho- phosphoric acid,96 and Westheimer has discussed the significance of pseudo- rotation in the hydrolysis of phosphate esters and related corn pound^.^^ The rate of the acid-catalysed hydrolysis of p-nitrophenyl diphenyl phosphate in aqueous dioxan goes through a maximum as a function of acid concen- trati~n.~~ This is not due to complete protonation of the substrate but is another example of a reaction for which negative salt-effects outweigh positive catalysis by protons.The rates of hydrolysis of a series of acyl phosphates with varying steric bulk in the acyl group have been studied as a function of acid and temperat~re.'~ The hydrolysis proceeds by an A-2 mechanism involving attack of solvent on the protonated acyl phosphate. The effect of variation of both nucleophile and leaving group on the reactivity of phosphate monoesters has been examined. loo The reactivity of the dianions depend strongly on the nature of the leaving group but only weakly on the bacicity of the nucleophile. For a sufficiently good leaving-group the Brsnsted co- efficient is zero and pyridines differing in basicity by several powers of ten attack the dianion of 2,4-dinitrophenyl phosphate at the same rate.The reactions of monoanions are very sensitive to nucleophile basicity and to the leaving- group as is consistent with an S,2 (P) mechanism. A reaction between an amine and a simple phosphate monoanion was demonstrated for the first time. Nucleophilic attack by fluoride ion on the monoanion of 2,4dinitro- phenyl phosphate was also observed. Both steric and polar substituent effects influence the rates of hydrolysis of 2,4-dichlorophenyl methyl N-alkylphosphoramidates.lo' The initial rapid pre-equilibrium protonation may occur at both oxygen and nitrogen. A variety of tentative mechanisms of hydrolysis are proposed.The hydrolysis of isopropyl methylphosphonofluoridate is catalysed by magnesium ions.'02 The active species is a magnesium hydroxo-complex which is slightly more active than the equivalent concentration of HO-. The catalytic effect could be due to either a 'super-acid' effect (17) or to hydrogen bonding (18). \ /.%PH2 Y N-o-H-~ II -Lo R-C -CH,-O-P< I 0-H Me y6 C. A. Bunton J. Chem. Educ. 1968,45,21. y7 F. H. Westheimer Accounts Chem. Res. 1968,1 70. C. A. Bunton S. J. Farber and E. J. Fendler J. Org.Chem. 1968,33 29. 99 D. R. Phillips and T. H. Fife J. Amer. Chem. SOC.,1968,90 6803. loo A. J. Kirby and A. G. Vargolis J. Chem. SOC.(B) 1968 135. lo' A. W. Garrison and C. E. Boozer J. Amer. Chem. SOC.,1968,90 3486. '02 J.Epstein and W. A. Mosler. J. Phvs. Chem. 1968. 72. 622. Reaction Mechanisms Neighbouring oxime-group participation has been reported" for the hydrolysis of p-nitrophenyl phenacyl methyl phosphonate oxime the rate- determining transition state (19) involving an oximate anion-catalysed water- mediated reaction. Whereas the hydrolysis of methyl N-cyclohexylphosphor- amidothioc chloride proceeds stereospecifically under neutral condition^,'^^ alkaline solvolysis gives a racemic product suggesting the existence of the planar intermediate (20). Me0 S Me0 'P' +HO-+ RNH/\C1 RN' 'Cl1 slow Me0 \ (racemic) product -!??-% /p=s RN (20) The concept of pseudorotation has been used to rationalise the observation of kinetic acceleration in cyclic phosphates and related compounds not only for ring-opening saponification but also for reactions not involving ring fission such as oxygen exchange and hydrolysis of groups external to the ring.97 Such reactions are considered to proceed through bipyramidal intermediates which can undergo pseudorotation.Thus ring strain in a five-membered cyclic phosphate is reduced without ring-opening in a transition state that has a naturally small 0-P-0 bond angle. Such a hypothesis explains the lack of kinetic acceleration in simple five-membered cyclic phosphinates which would require a trigonal-bipyramidal intermediate with an alkyl group in an energetically unfavourable apical position. '"9 Highly strained cyclic phosphinates for which an exceptionally large diminution in ring-strain accompanies the formation of the transition state do show the expected large rate-differences.lo Under alkaline conditions 1,2,2,3,4,4,-hexamethyl-l-phenylphosphetanium iodide"' (21; R' = R2= Me) and bromidelO'~''O undergo ring expansion to the five-membered phosphorus heterocycle (22).C. N. Lieske J. W. Hovance G. M. Steinberg and P. Blumberg Chem. Comm. 1968. 13. lo4 A. F. Gerrard and N. K. Hamer J. Chem. SOC.(B),1968 539. lo' G. A. Aksnes and K. Bergeson Acta. Chem. Scand. 1966,20,2508. E. A. Dennis and F. H. Westheimer J. Amer. Chem. SOC. 1966,88,3431. lo7 R. Kluger F. Kerst D. G. Lee E. A. Dennis and F. H. Westheimer J. Amer. Chem. SOC.,1967 89,3918. lo* S. E. Fishwick J. A. Flint W. Hawes and S. Trippett Chem.Comm. 1967 1113. log S. E. Cremer and R. J. Chorvat Tetrahedron Letters 1968,418. 'lo S. E. Cremer. Cheni. Comm.. 1968. 1132. J. G. Tillett H RZ MeUR' Me& Me D Me HH The alkaline hydrolysis of however 1,2,2,3-tetramethylphosphetaniurniodide (21 ; R' = Me RZ = H) forms the open-chain phosphme oxide (23).'" 0 Me Me I1 I I Ph-P-C-C-H I l l Me Me Me The formation of the acylic phosphine oxide is attributed to opening of the four-membered ring by fission of the P-CH bond in the trigonal-bipyramidal intermediate (24) rather than the P-CMe bond in (25) It is suggested that the CH carbanion from (24) can separate and add a proton but the less-stable CMe carbanion which is the only possible carbanion in the pentamethyl case attacks the phenyl group to give the rearranged product.The alkaline hydrolysis of 1-benzylphosphetanium bromide (21 ; R' = CH,Ph R2 = Me) proceeds with retention of configuration at phosphorus. ''' This is consistent with the view adopted above that the four-membered ring occupies an equatorial-apical position in the hydrolysis of phosphetanium salts. Usually the apical group opposed to 0-is expelled as the anion leading to inversion at phosphorus (26). 'I' S. E. Fishwick and J. A. Flint Chem. Comm. 1968 182. 'I2 W. Hawes and S. Trippett. Chem. Comm.. 1968. 295. Reaction Mechanisms H H H Me Me H In the benzyl case however the ring blocks loss of the benzyl anion from an apical position opposite to 0-.Loss of the benzyl anion must then occur either from an equatorial position of (27) or after pseudorotation to a new trigonal- bipyramidal intermediate (28) from an apical position.Both of these alternatives will lead to the observed retention of configuration at phosphorus. The four-membered cyclic phosphinate ester (29) hydrolyses in alkaline solution at about the same rate as triethyl phosphite,l13 whereas the relief of steric strain in a trigonal-bipyramidal intermediate in which the four- membered ring occupied an apical equatorial position would be expected to lead to rapid hydrolysis. Such a 'normal' rate of hydrolysis could arise from a combination of steric strain and retardation due to steric hindrance. One t-butyl group attached to phosphorus produces little steric hindrance to attack of OH-.However in the series of phosphinate esters RP(:O)*OEt there is a sharp fall-off in the rate of hydrolysis between R = Pr' and R = But 114 With two t-butyl groups attached to phosphorus one must occupy an equatorial position in the initial trigonal bipyramid (30). Bu* Me x \OMe Bu' But I 0;P-Y x x 'I3 K. Bergeson Acta. Chem. Sand.. 1967,21 1587. 'I4 W. Hawes and S. Trippett. C'heni. Comm.. 1968. 577 0' J. G. Tillett Due to the 'equatorial' t-butyl group there is substantial steric hindrance in the transition state leading to the formation of this intermediate to the approach of the nucleophile. With only one t-butyl on phosphorus ths can occupy an apical position as in (32).Pseudorotation to (33) then occurs before expulsion of the group Y from an apical position. Final confirmation of the view that the rates of alkaline hydrolysis of cyclic phosphinates are effected by competing steric acceleration and retardation comes from the observation of kinetic acceleration in (31) where the relief of steric strain is not accompanied by steric hindrance. (b) Sulphur Acids. The pH-rate profiles for the hydrolysis of nitrophenyl and dinitrophenyl sulphates are characterised by a plateau in the pH 4-12 region,' ''which is associated with a 'neutral' rate (k,). A linear free-energy plot of log ko against the pK of the corresponding phenol gave a slope of -1.2. A similar correlation for the acid-catalysed rate of hydrolysis (k& gave slopes in the range 0-22-0.26 indicating the relative insensitivity of the reaction to the electron-withdrawing power of the leaving group.The catalytic efficiency of the acids studied was in the order H,SO >HCIO >HCl. This differential behaviour was attributed to specific electrolyte effects. Plots of log k +H against aN were curved but a good linear correlation was obtained for the sulphates studied by plot.ting log k +H against H +C,+. The 4 values so obtained corresponded to little or no water participation in the rate- determining step. The solvolyses of 0-and p-carboxyphenyl sulphates in aqueous methanol have also been examined. 'The data suggests transition states of considerable sulphur trioxide character for catalysis by hydroxonium ions and the o-carboxy-group.The possibility of Lewis acid-base interactions influencing the product composition is also considered. As part of a study of kinetic acceleration in cyclic esters of sulphur-containing acids Kaiser and his group have shown"7 by oxygen-18 studies that the hydrolyses of the SS-dioxides of benzo[d][ 1,3,2]-dioxathiole (34) benzo[d- [1,2]oxathiole (35) and benzo[e][ 1,2]oxathiin (36) in alkaline solution proceed entirely with S-0 bond fission. mso* \ There was no evidence of reversible incorporation of l80 in the unchanged starting material. It has been suggested .that the 5-nitro-derivative of (34) is a convenient reagent for the 'titration' of a-chymotrypsin in the pH range 'I5 E. J. Fendler and J. H. Fendler J.Org. Chem. 1968,33 3852. S. J. Benkovic and P. A. Benkovic J. Amer Chem. SOC.,1968,90 2646. 'I7 E. T. Kaiser and 0.R. Zaborsky. J. Amer. Chem. SOC. 19hS. 90. 4626. Reaction Mechanisms 7-8. * The effect of structure variation on the hydrolysis of sultones has also been investigated. l9 Kaiser and his co-workers12' have recently reported on the extraordinary reactivity of vinylene sulphate compared to ethylene and dimethyl sulphate. It is of considerable interest to note that crystallographic determinations show that whilst the 0-SO bond angle in ethylene sulphate is 98.4" the corresponding angle in vinylene sulphate has the extremely 'low' value of 93.6" and so is therefore very close indeed to the 90"required to achieve a trigonal-bipyramidal transition state for alkaline hydrolysis.Analysis of the kinetic data for the alkaline hydrolysis of aliphatic and aromatic organic sulphites shows that kinetic acceleration in cyclic sulphites is due almost entirely to the differences in the entropies of activation of the cyclic esters and their open-chain analogues. 21 The acid-catalysed hydrolyses of cholesteryl methyl menthyl methyl dibornyl and 2-dinorbornyl sulphites all proceed by the well documented A-2 mechanism as indicated by kinetic acidity dependence and entropy of activation data.lz2 The order of effectiveness of mineral acids is HClO < H,SO < HCl which is attributed to concomitant acid and specific anion catalysis. Substituent Effects and Linear Free-energy Relationships.-Several attempts have been made to determine the relative importance of the direct and field effect components of the inductive effect.It has proved difficult however to provide an unambiguous answer to this important question because the two effects often act in the same direction. Wilson and Le~ng'~~ have attempted to obviate some of the difficulties by comparing the pK values of 4-substituted bicyclo[2.2.2]octane (37) and bicyclo[2.2.l]heptane-l-carboxylic acids (38) in which the direct effects would be expected to be very similar and the inductive effects different but calculable. (37) ''*J. H. Heidema and E. T. Kaiser Chem. Comm. 1968 300. '' E. M. Philbin. Chem. and Ind. 1968 688. F. P.Boer J. J. Flynn E. T. Kaiser 0.R. Zaborsky D.A. Tomalin A. E. Young and Y. C. Tong J. Amer. Chern. SOC.,1968,90 2970. 12' P. A. Bristow J. G. Tillett and D. E. Wiggins J. Chem. SOC.(B),1968 1360. 122 G. E. Manser A. D. Mesure J. G. Tillett and R. C. Young J. Chem. SOC.(B),1968,267. 123 C. F. Wilson and C. Leung J. Amer. Chem. SOC.,1968,90,336. J. G.Tillett The inductive model with a constant fall-off factorf with account of all three chains yields a substituent effect ratio p given by P = (2/f3) + (l/f2)/3/f3= (2 +f)/3 For a range offvalues of 2.0-3.0 the corresponding p-values are 1-33-1.67. The most realistic value forfwas assumed to be 2.7 to give a p-value of 1.57 which is independent of substituent. Use of the cavity model gives a predicted value of p = 1.20. The experimentally determined value of 1.175 suggests that transmission by the inductive effect occurs predominantly by the field effect and only to a small extent by inductive transmission.There is a growing interest in reversed dipolar substituent effects. From the following pK values of a series of 8-substituted 1-naphthoic acids124 in 80 % 2-methoxyethanol it can be seen that normally acid-strengthening substituents here have decreasing acidity H 6.40 C1 6-04 Br 6.16 NO2 6.00 and Me 5.99. Similar substituent effects were observed on the pK values of some cis-ortho-substituted a-phenylcinnamic acids. This decrease in acidity was attributed to decrease in the stability of the corresponding carboxylate anions (39) and (40) by a reversed dipolar effect. H/\ Ph The relative rates of reaction of these acids with diazodiphenylmethane support this interpretation.&war has critici~ed'~' Bowden and Parkin's work on the grounds that it is inconclusive since hydrogen-bonding in both 8-substituted 1-naphthoic acids and in o-substituted a-phenyl-cis-cinnamic acids could account for the observed effects. This could stabilise the acids relative to their conjugate bases and hence lower acidity. Clearly further experimental data is needed on this point. Another group of workers however have also produced independent evidence for a reversed dipolar effect in ths system.126 A plot of the pK values of a series of 8-substituted-1-naphthoic acids against (T has a p-value of -0.06. The corresponding values for substituents in the 5- 6- and 7-positions are 0.76,0.67 and 0.63 respectively.This abnormally low slope for substituents in the 8-position indicating an apparent absence of electronic effects on acidity is attributed to the almost exact cancellation of the normal polar effects of substituents by the reverse polar substituent effect. K. Bowden and D. C. Parkin Chem. Comm. 1968 75. M. J. S. Dewar Ckem. Comm. 1968 547. M. Hojo. K. Katsurakawa. and Z. Yoshida. Tetrahedron Letters 1968 1497. Reaction Mechanisms 89 A kinetic study of the alkaline ring-fission of substituted coumarins (Scheme 13) shows that electronic transmission to the reaction site occurs by way of both the cis-ethylenic and oxygen links.'27 + OH -pco; R R OH SCHEME 13 Substituent effects on fluorine-19 chemical-shifts in saturated systems have been analysed in terms of a n-inductive effect."* The relatively minor role of this latter effect has also been pointed out.129 The transmission of polar effects through the piperidine' 30 and quinoline' 31 rings has been investigated.Substituent effects on the ionization of rneta-substituted phenols,' 32 picric acids' 33 and monoalkylhydrazines' 34 have also been studied. The effect of ortho-substituents on the entropy of activation for the esterifica- tion of substituted benzoic acids by methanol has been analysed in terms of a 'bulk effect' which tends to decrease AS and steric inhibition of solvation of the transition state which tends to increase AS:. 35 Decrease of the enthalpy of activation by substituents was attributed to both a secondary steric effect of ortho-substituents and a steric inhibition of 'ring solvation' of the initial state which may be brought about by substituents in any position in the ring.The retarding effect of ortho-alkyl substituents is less marked in the analogous reaction of substituted phenyl acetic acids.136 This is attributed to a smaller primary steric effect in this system. The influence of solvents on the reaction of substituted benzoic acids with diazodiphenylmethane has been in~estigated.'~~ For a variety of solvents the rate correlation with dielectric constant has the form log k = 0.98 -(2.60)/(0.9 16 + 0.084~). The Hammett p-value correlated with dielectric constant in a similar manner p = 0.60 + 2.40/(0*75 + 0.2%).Specific inter- actions were observed for both correlations particularly in aprotic solvents. Liotta' 38 has reported an attempt to determine a,-parameters which are free from steric and solvation effects. A plot of log KOagainst log K from earlier data' ''for the extent of ion-pair formation of a series of substituted benzoic "-K. Bowden M. J. Hanson and G. R. Taylor. J. Chrnt. SOC.(B),1968 174. M. J. S. Dewar and T. G. Squires J. Amer. Chern. SOC.,1968,90,210. lZ9 C. W. L. Bevan T. A. Eucokpae and J. Hirst J. Chem. SOC. (B),1968,238. '30 T. D. Sotolova S. V. Bogatkov Yu. F. Malina B. V. Unkovski and E. M. Cherkasova Reakts. spos. org. Soedinenii 1968 5 160. 13' C. W. Donaldson and M. M. Joullic J. Org. Chem.1968,33 1504. 13' P. D. Bolton F. M. Hall and J. Kudryuski Austral. J. Chem. 1968 21 1541. 133 P. J. Pearce and R. J. J. Simkins Canud. J.Chem. 1968,46,241. 134 R. Pollet and H. vanden Eynde Bull. SOC. chim. belge. 1968,77,341. 135 N. B. Chapman M. G. Rodgers and J. Shorter J. Chem. SOC.(B),1968 157. N. B. Chapman M. G. Rodgers and J. Shorter J. Chem. SOC. (B) 1968 164. 131 A. Buckley N. B. Chapman M. R. J. Dack J. Shorter and H. M. Wall J. Chem. Soc. (B) 1968 631. C. L. Liotta Chem. Comm. 1968 338. 139 M. M. Davis and H. B. Hetzer. J. Rey. Nut. Bur. Siontl. 1958. 60.569. 90 J. G.Tillett acids towards 1,3-dihexylguanidine gave excellent correlation even for sub- stituents of widely differing steric bulk. This suggests that both primary and secondary steric effects are absent and that only polar effects are operative.Values of the parameter 0,"given by the correlation log (KX/K& = 1.41 log (K,/H& =o:,are as follows :H (OW) F (0-51), C1(0.82) Br (0.91) I (0-96) Me (-0.32) NO (2.18). Taft's o,*parameters are not a linear function of the values listed here which is a further indication that a values are not com- pletely free from steric effects. The rates of alkaline hydrolysis of a series of phenyl benzoates substituted in both the acyl and aryl moities have been measured.I4' A good o-p plot was obtained when the aryl group was kept constant. A poorer correlation obtained when the aryl group was varied could be improved if the p-nitrophenyl group was allocated a o-value of 0.89.Swain and Lupton14' have suggested that any set of substituent constants may be expressed in terms of a simple two-parameter equation of the form o =fF +rR where F and R are the field and resonance constants different for each substituent and f and r are empirical weighting factors independent of substituent but different for each set of substituent constants (om,op,a; o' etc.). It is assumed that r = 0 for 0'(from ionization of 4-substituted bicyclo- [2,2,2]octanecarboxylic acids) and R = 0 for the Me,N substituent. The assumption that the field effects of a particular substituent in both rneta-and para-positions are equal is shown to be incorrect. Weighting factors have been calculated for various reaction sets by computer analysis the average correlation coefficient being 0.96'7.It is interesting to note that this correlation is not significantly increased by the use of an additional variable. The correla- tion is exceptionally high for both the ionization of 4-substituted bicyclo- [2,2,2]octane-l-carboxylic acids (0.990) and the alkaline hydrolysis of ethyl arylacetates (0.992). A further example of the way in which linear free-energy relationships sometimes disperse into separate lines characteristic of different types of substituent is illustrated by the reaction of trivalent phosphorus compounds with phenyl azide.142 The log k versus a* points lie on two parallel straight lines. The introduction of an oxygen atom changing from Ar,P to Ar,POR causes a sharp discontinuity whereas second and third oxygens [on going to ArP(OR) and P(OR),] do not.Hammett o' -values have been calc~lated'~~ by an extension of the localised- orbital model for the determination of substituent electronic effects on 7c-electron systems. An inductive parameter model of substituent effects has been adopted for HMO theory for monosubstituted anthraquinones. 144 An approach to linear free-energy relationships by non-equilibrium thermodynamics has also been re~0rted.l~~ I4O J. F. Krisch W. Clewell and A. Simon J. Org. Chem. 1968,33 127. 14' C.G. Swain and E. C. Lupton J. Amer. Chem. SOC.,1968,90,4328. 14' R.D.Temple and J. E. Leffler Tetrahedron Letters 1968 1893. 143 M.Godfrey J. Chem. SOC. (B) 1968,75. 144 W.Kemula and M. T. Krygowski. Bull. Acad. polon.Sci. Ser. Sci. chim.. 1967.15.479. Reaction Mechanisms 91 Further correlations of mass-spectral ion intensities with o-values have been reported. 146-149 The earlier assumption that a precise o-correlation implied that decomposition of e.g. substituted benzophenones (PhCO C6H4Y+*+PhCO+ + C6H4Y0) produces C7H50+ ions that are identical in average internal energies has been shown to be incorrect.”’ The Hammett relationship has also been applied to enzyme kinetics’” and in heterogeneous catalysis.’ 52 Electrophilic Substitution.-Another monograph on aromatic substitution reactions” and a review of electrophilic substitution in heteroaromatic compounds154 were published during 1968. Ridd and his co-workers have published further details of their work on the substituent effect of positive + poles.The rates of meta-nitration of ions Ph[CH,],NMe (n = 0 1 2 or 3) in aqueous sulphuric acid are consistent with the transmission of polar effects mainly by a direct-field effect rather than by the classical inductive mechanism. The variation of the enthalpy and entropy of activation with the number of + methylene groups is also consistent with this view. The reactivity of PhXMe, where X = N P As or Sb towards nitration in sulphuric acid increases steadily with atomic weight of the atom bearing the positive charge.ls6 The amount of para-substitution is greater for the AMe group than for SbMei and passes through a minimum with phosphorus and arsenic poles. In contrast the amount of ortho-substitution is much greater for the antimony pole than for nitrogen.These differences are attributed to the effect of p- and d-orbital interactions on the mesomeric effect. A kinetic study of the silver ion-catalysed chlorination and bromination of dimethyl-sulphonium and -selenonium ions157 shows that whilst the meta :para ratio for chlorination bromination and nitration are very similar the ortho :para ratios for chlorination and bromination are much higher than for nitration Even in highly electron-demanding situations such as the nitration in 98 :< H2S04 of the 4-alkylphenyltrimethylammoniumions alkyl groups influence nitration by electron release in the inductive order. The rates of nitration by nitronium ion of benzene and other reactive species reach a limiting value in both sulphuric and perchloric acids.lS9 This limiting 14’ T.Suzuki M. Seno and T. Yamabe J. Chem. SOC. Japan 1968,89 136. 146 R. A. W. Johnstone and D. W. Payling Chem. Comm. 1968 601. 147 M. M. Bursey J. Org. Mass. Spec. 1968 1,31. 148 F. W. McLafferty and M. M. Bursey J. Org. Chem. 1968,33 124. 149 M. M. Bursey and E. S. Wolfe J. Org. Mass Spec. 1968,-1 543. 150 M. L. Cross and F. W. McLafferty Chem. Comm. 1968 254. E. A. Zeller P. F. Palmberg and B. H. Babu Biochem. J. 1967 105,41. T. Hishida T. Uchijuma and Y. Yoneda J. Catalysis. 1968 11 71. L. M. Stock ‘Aromatic Substitution Reactions,’ Prentice-Hall New Jersey 1968. J. H. Ridd 2.Chem. 1968 (I 201. T. A. Modro and J. H. Ridd J. Chem. SOC. (B) 1968,528. A.Grastraminza T. A. Modro J. H. Ridd and J. H. P. Utley J. Chem. SOC.(E) 1968 534. 157 H. M. Gilow R. B. Camp and E. C. Clifton J. Org. Chem. 1968,33 230. J. H. P. Utley and T. A. Vaughan J. Chem. SOC. (B),1968 196. 159 R. G. Coombes. R. B. Moodie. and K. Schofield. J. Chem. SOC.(B).1968. 800. D J. G. Tillett rate is ascribed to the rate of encounter of nitronium ions and aromatic sub- strate (k3in Scheme 14) HNO + H+ k NO; + H20 k2 k3 NO; + Ar ====(encounter pair) k k5 (e.p.) -products SCHEME 14 If the encounter pair is treated as a transient intermediate steady-state treat- ment leads to the expression For highly reactive substrates k5 is large and k2(obs) is determined only by the concentration ratio and by the encounter rate k,.In sulphuric acid up to 68% the rate of nitration of benzene is less than a fortieth of the theoretical limit set by the encounter rate whilst in 80% sulphuric acid the observed rate approaches to within a sixth of the encounter rate. This suggests that meaningful comparisons of the reactivity of deactivated substrates can be made in sulphuric acid up to 68% but above this such comparisons may well be open to question. The rates of nitration with anhydrous nitric acid in carbon tetrachloride of benzene toluene p-xylene and mesitylene are all very similar.16* The reaction is zero order in aromatic substrate and of order 6 in nitric acid. This latter feature suggests that the rate-determining step involves desolvation of a solvated ionic or polar species and is the same for all the substrates studied.Consistent with this view is the observation that the rate of nitration of mesity- lene shows a substantial increase in going from 40"to O" since solvation phenomena are known to be very sensitive to temperature. Both 2-phenylpyridine and 2-phenylpyridine-N-oxideundergo nitration as their conjugate acids (41) and (42).16' I I H OH lh0 T. G. Bonner R. A. Hancock and F. R. Rolle Tetrahedron Letters 1968 1665. 16' A. R. Katritzky and M. Kingsland. J. Chem. Soc. (B). 1968. 862. React ion Mechanisms 93 The partial rate factors show overall similarity to those of the benzyltrimethyl- ammonium cation suggesting that the inductive effect is again more important than the mesomeric effect.Comparison of the rates of nitration of cinnoline and 2-methylcinnolinium perchlorate suggest that the former compound also undergoes nitration as the 2-cinnolinium cation. 162 The nitration of cinnoline 2-oxide occurs through both neutral and conjugate acid species. 163 Reaction through the cation leads mainly to 5-and 8-nitrocinnoline whilst nitration of the neutral species leads mainly to the 6-nitro-derivative. The kinetics of the two processes involved in the nitration of quinoline 1-oxide leading to the formation of the 5-and 8-nitro-compounds at lower temperature and to the 4-nitro-compound at higher temperature have been separated and have been shown to be due to involve the 1-hydroxyquinolinium cation and the free base respectively.Studies of the nitration of substituted pyri- dines164,165 have also been reported. The nitration of acetanilides with mixed acids results in attack para to the acetamido-group whereas the use of acetyl nitrate or nitronium fluoroborate produces predominantly the ortho-substituted product. 166 It is suggested that ortho-substitution results from S,2 displacement by an electron pair (on nitrogen or on carbonyl oxygen) on the species N02X (X = BF or OAc) leading to formation of the most readily accessible o-complex (Scheme 15) while the para-substituent favoured in mixed acids results from attack on the conjugated acid of acetanilide. No clear distinction between the two S,2 mechanisms can be made at present. Part of the driving force for ortho-nitration is thought to be the strong hydrogen- bonding interaction between the nitro-group and the acetamide hydrogen atom.This is supported by the observation that the major product in the acetyl nitrate nitration of N-methylacetamide-where such hydrogen bonding is absent-is 4-nitro-N-methylacetanilide. A variety of N-nitropyridinium tetrafluoroborates have been used to effect nitration of aromatic substrates under mild conditions in homogeneous solution.167 Thus a-picolinium tetrafluoroborate nitrates toluene readily and quantitatively at room temperature. The 2,6-lutidine salt is even more reactive. These salts show considerable substrate selectivity k(toluene)/ k(benzene) being 36.5 and 39-0for the picolinium and lutidine salts respectively.The kinetic isotope effect for the nitro-deprotonation of a series of 1-sub- stituted-2,4,6-tri-t-butylbenzenesvaries' 68 with the substituent as follows H(k,/k 1.0). F (2-3) NO (3.0) and CH (3-7). This suggests that there can be R. B. Moodie E. A. Qureshi K. Schofield and J. T. Cleghorn J. Chem. Soc. (B) 1968 312. 163 R. B. Moodie E. A. Qureshi and K. Schofield J. Chem. SOC.(B),1968 316. 164 R. C. de Selms J. Org. Chem. 1968,33,478. L. D. Smirnov V. P. Lezina B. E. Zaitsev and K. M. Dyumaev Zzoest. Akad. Nauk. SSSR Ser. khim. 1968 1652. B. M. Lynch C. M. Chen and Yak-Yung Wigfield Canad. J. Chem. 1968,46 1141. C. A. Cupas and R. L. Pearson J. Amer. Chem. SOC.,1968,90,4742. 16' P. C. Myhre. M. Beng. and L. L. James. J. Amer. Chem. SOC.. 1968.90.2105.J. G. Tillett / Me I SCHEME 15 a change-over from the rapid proton transfer envisaged in the usual two-stage mechanisms of nitration to a slow rate-determining proton transfer 702 k2 ArH + NO; kl Ar’ -ArNO + H+ k-1 \ slow H The observed isotope effect is attributed to differential increase of k compared to k- by steric repulsion effects at C-1. The electron-releasing effect of the 5-acetamido-group is insufficient to overcome the deactivating influence of the 2-phenyl group of the pyrimidine ring169 and the only product of nitration is the rn-nitro-derivative (43). The nitration of various polycylic compounds has been rep~rted.”~-’~~ (43) M. P. L. Caton and J. F. W. McOmie J. Chem. SOC.(C),1968 836. A. Davies and K.D. Warren J. Chem. SOC.(B),1968 1337. 17’ V. V. Zverev G. P. Shronin and I. D. Morocova Zhur. org. Khim. 1968,4 148 1236. 17’ C. C. Cook and F. K. Sutcliffe J. Chem. SOC.(C),1968,957. H. F. Andrew N. Campbell J. T. Craig and K. J. Nichol J. Chem. SOC.(C),1968 1761. 174 I. L. Klundt and W. K. Hoya J. Org. Chem. 1968,33 3327. Reaction Mechanisms OH 9 6+ HNO 0 - - 6 Qo NOH The nitration of alkyl substituted 2,3-dihydro-1,4-diazepiniumsalts is the unusual example of a cation reacting with another positive species.'75 The radiation-induced nitration of benzene with anhydrous potassium nitrate under heterogeneous conditions gives a 95 % yield of nitrobenzene. 176 The primary isotope effect (k,/k ca. 3.8) observed for the nitrosation of phenol and the acidity dependence for this reaction are consistent with the formation of a dienone intermediate (44) which can undergo decomposition spontaneously or by an acid-catalysed pathway.177 A further example of transannular directive influences has been reported. l7* The bromination of a 4-bromo [2,2]paracyclophane results in seven times more pseudo-ortho and pseudo-para than pseudo-meta compound and the ortho-and para-positions of the starting material carry more negative charge than the rneta-positions C(45) and (46)l. The resonance form (47) is clearly unimportant. The observed products suggest that the product-determining step is proton transfer to an acceptor site on the originally substituted ring. On the approach of the electrophile a proton is transferred from ring to ring and a proton then departs from the face of the unsubstituted ring.The reaction sequence leading to the formation of the pseudo-para-product is shown in Scheme 16. De la Mare and his co-workers have recently shown that chlorination of naphthalene leads to products of both substitution and addition. 179 Similarly the chlorination of 2,4dichloro-l-naphthol leads to the formation of (48) and (49). 175 A. M. Gorringe D. Lloyd D. R. Marshall and L. A. Mulligan Chem. and Ind. 1968 130. 17' W. W. Epstein R. N. Kurt and D. MacGregor Chem. Comm. 1968 1190. 177 B. C. Challis and A. J. Lawson Chem. Comm. 1968 818. 178 H. T. Reich and D. J. Cram J. Amer. Chem. Soc. 1968,90 1365. 179 P. B. D. de la Mare M.D. Johnson J. S. Lomas and V. Sanchez del Olmo J. Chem. SOC.(B) 1966,827. 180 P. B. D. de la Mare and H. Suzuki. J. Chem. SOC.(C),1968.648. J. G Tillett E+ fast Br@ H SCHEME 16 The side-chain chlorination of 2,3-dirnethylbenzothiopher1~'~has been considered to involve the formation of either the ion-pair (50) or the adduct (51)where chlorine adds across a double-bond. A tetrachloride adduct is also formed in the chlorination of 1-iodo-2-naph- thol. 82 The products of the bromination of trihydroxynaphthalene are thought to arise from initial addition across the carbon-carbon double-bond. The bromination of 2-phenanthrol has also been investigated. The rates of chlorination of some substituted rn-dimethoxybenzenes correlate with o+-values.185 The high p-value confirms the heterolytic nature of the rate-determining step.The reactive chlorinating species in the sulphenyl chloride chlorination of a number of alkylbenzenes is shown to be molecular E. Baciocchi and L. Mandolini J. Chem. SOC. (B),1968,397. H. Suzuki Bull. Chem. SOC. Japan 1968,41 1265. lE3 B. S. Balgir and R. H. Prager Austral. J. Chem. 1968,21 2327. E. Ota and K. Iwamoto J. Synthetic Org. Chem. Japan 1968,26 161. lS5 R. Bo1ton.J. Chem. SOC.(B).1968. 712. Reaction Mechanisms 97 sulphuryl chloride. 186 Molecular chlorine formed by dissociation of the reagent however provides a second minor chlorination pathway. The kinetics of bromination of alkybenzenes,' 87 1,5-dimethylnaphthalene,' 88 and some aromatic amine~'~~.have also been recorded. The acid-catalysed bromination of some aromatic compounds has also been studied. 19'* 192 The rates of iodination of nitrobenzene and benzoic acid with the tri-iodide cation have been investigated. l9 A two-stage mechanism is proposed to explain the observation of a kinetic isotope effect (k,/k ca. 3.2). Katritzky and his co-workers have reported studies of the acid-catalysed hydrogen exchange of 4-substituted anilines,lg4 3,5-dimethylphen01,'~~ and some pyridazine derivatives. lY6 The rates of detritiation of some substituted tritionaphthalenes' 97 and thiophens198 have also been reported. Kinetic studies of aprotic diazotisation of arylamine~'~~~~~~ and a further study of the mechanism of aromatic sulphonation201 have also been carried out.Nucleophilic Aromatic Substitution.-Several investigations reported this year provide further evidence for the existence of Meisenheimer complexes as intermediates in nucleophilic aromatic displacement reactions. The complex (52) obtained by the attack of methoxide ion on l-methoxy-2,4-dinitronaph-thalene is more stable than that formed with 3.4-dinitroanisole but less stable than the corresponding picryl complex.202. 203 CN (53) The crystalline salt isolatedZVs after the addition of methoxide ion to 4-CyanO- 2,4-dinitroanisole was shown to have the structure (53). The stability of Meisenheimer complexes clearly depends significantly on the ability of the 186 R. Bolton J. Chem. SOC.(B),1968 714. J.E. Dubois P. Alcais and F. Rottenberg J. Org. Chern. 1968,33 439. E. Berliner J. B. Kim and M. Link J. Org. Chem. 1968,33 1160. 189 J. E. Dubois. P. Alcais. and G. Barbeis. Bull. Soc. chinr. Frrrnce. 1968. 605. 61 1. I9O J. E. Dubois R. Uzan and P. Alcais Bull. Soc. chim. France 1968 617. 19' Y. Furaya A. Morita and I. Urasaki Bull. Chem. SOC.Japan 1968,41,957. 192 R. M. Kellogg A. P. Schaags E. T. Harper and H. Wynberg J. Org. Chem. 1968 33 2902. 193 J. Arotsky A. C. Darby and J. B. A. Hamilton J. Chem. SOC.(B),1968 739. 194 G. P. Bean and A. R. Katritzky J. Chem. SOC.(B),1968,864. 19' P. Bellingham C. D. Johnson and A. R. Katritzky J. Chem. SOC.,1968 866. 196 A. R. Katritzky and I. Pojarlieff J. Chem. SOC.(B),1968 873. 19' C. Eaborn P. Golborn R.E. Spillett and R. Taylor J. Chem. SOC.(B),1968 1112. 198 A. R. Butler and C. Eaborn J. Chem. SOC.(B),1968,370. 199 L. Friedman and J. F. Chlebowski J. Org. Chem. 1968,33 1633 1636. 2oo 0.Sziman and A. Messmer Tetrahedron Letters 1968 1625. 201 C. W. F. Kort and H. Cerfontain Rec. Trav. chim. 1968,87 24. 202 J. H. Fendler E. H. Fendler W. E. Bryne and C. E. Griffin J. Org. Chem. 1968 33 977. 203 C. F. Bernasconi J. Amer. Chem. SOC.,1968,90,4982. 204 J. E. Dickerson L. K. Dyall. and V. A. Pickles Austral. J. Chem.. 1968,21. 1267. J. G. Tillett ring substituents to accept a negative charge. Servis showed205 that the reaction of methyl picrate with methoxide ion in dimethyl sulphoxide initially yields the 1,3-dimethoxycyclohexadienylide (54).This undergoes a rapid conversion to the thermodynamically more stable complex (55). OMe NO2 OMe Crampton and Gold206 had earlier suggested that the reason for this isomerisa- tion is that whilst (55) is a less strained structure than methyl picrate the transition state leading to its formation is more strained than for (54).It should prove possible to find other examples which illustrate this interplay between kinetic and thermodynamic control. Until this year however no further examples of 1,3complex formation have been reported. Fendler et al.,207followed the course of the reaction of 2-cyano-4,6-dimethoxyanisole with methoxide ion by 'H n.m.r. spectroscopy. The spectrum of the known complex (56) was observed together with that of the 1,3-complex (57) which had a half-life of approximately 1 hr.OMe Similar observations were made in studies of the reactions of methoxide ion with 4-cyano-2,6-dinitroanisoleand 2,4-dicyano-6-nitroanisole. In both cases the 1,3-complexes are again formed initially and then undergo conversion to the isomeric 1,l-complexes. The isolation of the 1,l-complex of the former compound has also been reported by other workers (see above).204 The bright red colour formed on the addition of sodium hydroxide to an acetone solution of l-(~-hydroxyethoxy)-2,4-dinitrobenzene20s was thought to be due to the formation of a spiro-Meisenheimer complex (58). 205 K. L. Servis J. Amer. Chem. SOC. 1967,89 1508. 206 M. R. Crampton and V. Gold J. Chem. SOC.(B),1966 893. 207 E.J. Fendler C. E. Griffin and J. H. Fendler Tetrahedron Letters 1968 5631. 208 F. J. Pollitt and B. C. Saunders J. Chem. Soc. 1964 1132. Reaction Mechanisms Subsequently the analogous trinitro-Meisenheimer complex (59) was isolated from the reaction mixtures of 1-(P-hydroxyethoxy)2,4,6-trinitrobenzeneand sodium gly~ollate.~'~ The rate of decomposition of (59) in aqueous sodium hydroxide was shown to be several orders of magnitude slower than for noncyclic 1,l-dialkoxy-Meisenheimer complexes [e.g. (53)l. Fendler et al.21 have now reported the synthesis and isolation of the crystalline complexes (58),(60),and (61). N (60) (61) (62) The i.r. and 'H n.m.r. spectra substantiate the postulated structures. This provides compelling evidence of sp3-hybridization at C-1 of the cyclohexa- dienyl system of Meisenheimer complexes because the existence of spiro- complexes requires such hybridisation.Several investigators have reported evidence for the formation of Meisen-heimer complexes in nucleophilic displacement reactions of N-heteroaromatic substrates e.g. for the reaction of sodium methoxide with 4-methoxy-3,5- 3,5-dinitro~yridine,~'~ dinitr~pyridine,~~~-~" and 2-dimethylamino-3,5-di-nitropyridine.212 Fyffe2 l2 has also postulated the formation of a spiro Meisen- heimer complex (62) formed from the reaction between sodium methoxide and 2-(2' -hydroxyethoxy)-3,5-dini tropyridine. Kinetic studies of the effects of base catalysts on nucleophilic aromatic displacement have led to the adoption of a two-step mechanism for such reactions involving the formation of an addition intermediate which can decompose either spontaneously (k2)or by a base-catalysed pathway2 l3 (kB).'09 R. Foster C. A. Fyffe and J. W. Morris Rec. Trav. chim. 1965,84,516. *lo E. J. Fendler J. H. Fendler W. E. Bryne and C. E. Griffin J. Org.Chem. 1968,33,4141. '11 G.Illuminati and F. Stegel Tetrahedron Letters 1968,4169. '"C. A. Fyffe Tetrahedron Letters 1968 659. '13 J. F. Bunnett and R. H. Garst J. Amer. Chem. SOC.,1965,87 3875. 100 J. G. Tillett SCHEME 17 Most studies of the effect of steric hindrance on the entering and leaving group have been carried out in aprotic solvents. A recent of the reaction of various amines with halogeno-nitrobenzenes in a protic solvent (methanol) in which the formation step (k,) is thought to be rate-determining indicates that steric effects are much less important than with aliphatic sub- strates.The kinetics of the reversible reaction of piperidine with 2,4-dinitroani- sole have also been studied215 in this solvent. The relative reactivities in dimethyl sulphoxide of a series of substituted amines towards various fluoro- and chloro-nitroaromatics do not vary greatly with change of substrate.2 The ortho:para ratio also changes little with nucleophile. The facts are in- terpreted in terms of a nearly tetrahedral transition-state in which steric inhibition of resonance of the ortho-nitro-group is not pronounced. The kinetic form of the rate equation for the catalysis by added phenol on the reaction between piperidine and 1-fluoro-2,4-dinitrobenzene in benzene as solvent is given by:217 Rate/"ArF] CPi~l,ree = ko + kpip[Pi~lfree+ khOH[ArOHlfree + ksa,tCSaltl (where salt = piperidino-phenoxide).The first term (k,) represents the uncatalysed decomposition of the addition intermediate and the last three terms its decomposition catalysed by base phenol and salt. In contrast the reaction of piperidine with l-chloro-2,4- dinitrobenzene for which the rate-determining step is thought to be formation of the addition intermediate is not catalysed by either phenols or salts. The term which is first-order in amine concentration is attributed to intramolecular catalysis of the reaction by the ortho-nitro-group. Catalysis by free phenol is almost independent of any substituent which suggests that phenols act as a bifunctional catalyd3 for piperidino-defluorination.Powerful catalysis of the rate by tetra-n-butylammonium chloride and the complete absence of any effect with the corresponding perchlorate indicate G. Bartoli L. Di Nunno and P. E. Todesco Tetrahedron Letters 1968 2369. 215 J. F. Bunnett and R. Xi.Garst J. Org. Chem. 1968,33,2320 F. Pietra and F. Del Cima J. Org. Chem. 1968,33 1411. *" F. Pietra and D. Vitali J. Chern. Sac. (B). 1968. 1318. Reaction Mechanisms that the ‘salt’ is involved in catalysing decomposition of the intermediate. The analogous reaction with l-chloro-2,4-dinitrobenzene is not affected by the addition of added chloride.The anion of the salt must be jnvolved in proton abstraction because of the lack of this effect with non-basic anions like per- chlorate. It is interesting to compare the catalytic effect of quaternary ammonium salts on this reaction with that on the mutarotation of glucose in benzene (loc. cit). An alternative mechanism for base catalysis in nucleophilic aromatic displacements has recently been A study of the relative activating + + powers of the NMe,O NMe, and NO groups towards displacement of fluorine by methoxide ion in fluoroaromatics has led to the conclusion that electron displacement through the aromatic ring is indeed partly transmitted by a small 7c-inductive effect.129 The first account of the displacement of a nitro-group from an unactivated nitro-compound has been reported.Triethyl phosphite will displace the nitro-group from p-nitrotoluene. This is not considered however to involve direct displacement of the nitro-group but to be initiated by nucleophilic attack on an oxygen atom of the nitro-group. Photochemically induced nucleophilic displacements continue to be reported. The first example of the displacement of a dianionic species from an aromatic ring is provided by the displacement of the sulphoxylate anion (SO,’-) from sodium toluene-p-sulphinate with methyl lithium.220 Values of the kinetic solvent isotope effect for the reaction of 2,4-dinitro- chlorobenzene with ethoxide ion and pyridine”’ [k(EtOD)/k(EtOH)] = 1-84 and 1.30 for EtO- and pyridine respectively) were in reasonable accord with those predicted by the Bunton-Shiner treatment.222 Molecular orbital calculations have been used in an attempt to interpret the kinetics of aromatic replacement reaction^."^ An attempt has also been made to correlate the reactivity of aromatic and aliphatic substrates towards nucleophiles in dipolar aprotic solvents.224 ’’’ S.D. Ross Tetrahedron Letters 1968,4699. 2’9 J. I. G. Cadogan D. J. Sears and D. M. Smith Chem. Comm. 1968 1107. 220 R. H. Shapiro and K. Tomer Chem. Comm. 1968,460. 221 1. R. Bellobono P. Beltrame M. G. Cattanla and M. Sunonetta Tetrahedron Letters 1968 2673. 222 C. A. Bunton and V. J. Shiner J. Amer. Chem. SOC.,1961,83,42,3207. 223 P. Beltrame P. L. Beltrame and M. Simonetta Tetrahedron 1968,24,3043. 224 G.Bartoli and P. E. Todesco Tetrahedron Letters 1968,4867.

ISSN:0069-3030    

DOI:10.1039/OC9686500067

出版商:RSC    

年代:1968

数据来源: RSC

摘要:

3 (Part ii) REACTION MECHANISMS By N. S. Isaacs (Department of Chemistry The University Whiteknights Park Reading) Stable Carbonium Ions.-Rates of reaction of the tris-(p-methoxypheny1)- carbonium ion with water hydroxide ion and ammonia have been measured by a stopped-flow technique. The second-order rate constants are 0.28 4-6 x lo3 and 2.1 x lo3 1. mole-1 set.-' respectively and a negative salt effect was observed. The spectroscopic properties of a large number of sub-stituted and bridged trityl cations have been recorded2 and resolution of the first asymmetric carbonium ion (1)(by virtue of restricted rotation) has been achieved. The n.m.r. spectra of some diphenyl (2-and 3-pyridinium)methyl dications (2) have shown that the heterocyclic ring protons are more deshielded than the phenyl proton^.^ Among new aromatic cations are the ditropylium dication (3) which exhibits a singlet n.m.r.spectrum at z 0.05 (cf:the tropylium ion at z 1-31) and is assumed to be twisted about the central bond.5 The tri-t-butylcyclopropenium ion appears to be less stable (pKR+ = 6.1) than the tri-isopropyl analogue (pKR+= 7.0) as measured by titration against sodium hydroxide in 50% aqueous acetonitrile.6 How much this is due to steric crowding and how much to a reduction in electron release by the t-butyl group is difficult to assess but it may be relevant that the heptaphenyltropylium ion is less stable than ' E. A. Hill and W. J. Mueller Tetrahedron Letters 1968 2565. R Breslow S.Garratt L. Kaplan and D. La Follette J.Amer. Chem. Soc. 1968 90 4051 ; R. Breslow L. Kaplan and D. La Follette ibid. p. 4056. B. L. Murr and L. W. Feller J. Amer. Chem. SOC.,1968,90,2966. G. A. Olah and M. Calin J. Amer. Chem. SOC.,1968,90,943. I. S. Akhrem E. I. Fedin B. A Kvasov and M. E. Vol'pin Tetrahedron Letters 1967 5265. J. Ciabat'toni and E. C. Nathan J. Arner. Chem. SOC.,1968,90,4495. 104 N. S. Isaacs the corresponding hexaphenyl compound which is almost certainly due to crowding and lack of coplanarity of the rings.7 The n.m.r. spectra of the benzo-(4)* and dibenzo-homotropylium ions' have been recorded for sul- phuric acid solutions at room temperature. The em-and endu-methylene -73 HO.70 0.80 H .1.29 protons are quite distinct being shielded and deshieIded respectively by the aromatic ring current.At 0" slow deuterium exchange of the latter is observed in deuteriosulphuric acid but only at quite elevated temperatures does general deuterium exchange occur. The stable carboxonium ion (5) has been reported.'O The all-trans-retinene cation (A,,, 600 nm.) was observed to be stable for several minutes in aqueous acidic solution at 4" its low reactivity being at- tributable to the sharing of the charge by the 11 carbon atoms of the con- jugated chain. '' The i.r. spectra of the acetylium and trideuteroacetylium ions (as hexafluoroantimonates) show a carbonyl-stretching frequency in the vicinity of 2300 cm.- l2 indicating considerable triple-bond character (oxonium character) of this species; this was confirmed by X-ray diffraction measurements of the bond lengths.A number of 3-phenyl-3-benzocyclo-butenyl cations (6) have been observed by n.m.r. spectroscopy in sulphuric acid. From a consideration of the pK,+ values these ions appear to be more stable than the analogous benzhydryl cations possibly because one ring at least and perhaps both are coplanar with the positive centre.13 7.7 Me 1.5-2.0 Cl Me (6) ' M. A. Battiste and T. J. Barton Tetrahedron Letters 1968,2951. W. Merk and R. Pettit J. Amer. Chem. SOC. 1968,90 814. R. F. Childs and S. Winstein J. Amer. Chem. SOC.,1967,89 6348. lo K. Dimroth and W. Mach Angew. Chem. Internat. Edn 1968,7,461. l1 P. E. Blatz and D. L. Pippert,J. Amer. Chem. SOC. 1968,90 1296. l2 P. N. Gates and D. Steele J.Mol. Struct. 1968 1 349. l3 H. Hart and J. A. Hartlage,J. Amer. Chem. Soc. 1967,W. 6672. Reaction Mechanisms 105 Allylic cations are greatly stabilised by substituent chlorine. Pentachloroallyl tetrachl~roaluminate'~has been isolated as bronze crystals (hmax 435 nm.) and the n.m.r. spectrum of the 1,2,3-trichloroallyl cation has been observed in solution (7).15 The n.q.r. spectrum of the trichlorocyclopropenium ion has been studied'6 and has been interpreted as showing 16% n-character in each C-CI bond and from 50-75% of the excess positive charge carried on chlorine. Strong electrolyte character is exhibited by trityl hexachloroant- imonate in dichloromet hane solution as judged by conductance measure-ment~.~~ The i.r. spectrum of the benzoyl cation1* has been reported and crystalline acetyl- and thiobenzoyl-hexafluoroantimonatesl9 have been iso- lated and have been shown to be ionic.The latter compound is a highly reactive electrophile and with benzene gives thiobenzophenone in a rare example of a Friedel-Crafts thione synthesis (8). A significant volume of new work has PhC=S + -g+PhCSPh (8) appeared concerning the properties of highly acidic solvents such as antimony pentafluoride-fluorosulphonic acid ; the subject has been reviewed by Gilles- pie.20 Cyclopropane at -100" in this system shows an n.m.r. spectrum con- sisting of two closely spaced doublets (z 7.7 and 7.9) and a septuplet (T 3.6). These signals were tentatively assigned to a protonated cyclopropane.2 At higher temperatures decomposition to the 1-methylethyl cation and various C-4 and C-5 cations occurs.Cyclobutane under the same conditions undergoes a hydride loss to give a cyclobutyl (or cyclopropylmethyl) cation also unstable above -loo" while the same behaviour is shown by cyclopentane up to -10". The greater stability of this ion compared with cyclobutyl would be expected on grounds of ring strain. The cyclopropyl cation can be generated and shows only a singlet n.m.r. signal. This evidently indicates that rapid hydride migration around the ring is taking place. However above -lo",ring-opening and alkylation leads to the pentyl cation. The same stable cation is formed when either norbornane norborenene tricyclane or norbonyl halides are dissolved in SbF,-HF-FSO 3H.22 The structure suggested for this species is (9) on the grounds that the Raman spectrum shows similarities to that of tricyclane (lo) the n.m.r.spectrum being in agreement. Halogenocyclopro- panes are pr~tonated~~ at -78" but rearrange to halogenium ions (1l),species l4 K. Kirchhoff F. Boberg D. Friedemann and G. R. Schultze Tetrahedron Letters 1967 3861 P. T. Kwitowski Diss Abs. 1967,28B 583. K. Kirchhoff F. Boberg and D. Friedemann Tetrahedron Letters 1968,2935. l6 E. A. C. Lucken and C. Mazeline J. Chem. Soc. (A),1968 153. N. Kalfoglou and M. Szwarc J. Phys. Chem. 1968,72 2233. H. Perkampus and W. Weiss Angew. Chem. 1968,80,40. l9 (a)F. P. DeBoer J. Amer. Chem Soc. 1968,90,6706;(b)E. Linder and H. G. Karmann Angew. Chem. Internat.Edn. 1968 548. 2o R. J. Gillespie Accounts Chem. Res. 1968 1 202. 21 G. A. Olah and J. Lukas J. Amer. Chem. SOC.,1968,90,933,938. 22 G. A. Olah A. Commeyras and C. Y. Liu J. Amer. Chem. SOC.,1968,90,3882. 23 G. A. Olah and J. M. Bollinger,J. Amer. Chem. Soc. 1968,90,6082. 106 N. S. Isaacs Me Me H (9) 00) (11) observed previo~sly,'~ which in turn above -10" eliminate Hhal to give a species the spectrum of which is compatible with the 2,3-dimethylbut-3- enyl cation (12). This appears to have a localised structure which indicates that an allylic interaction provides less stabilisation than a tertiary position. The n.m.r. spectra of a number of ally1 cations have been studied over a range of temperatures and the energy and entropy barriers to rotation about the carbonxarbon bonds have been estimated to be in the range E = 4-6 kcal.mole- and ASs = ca -30 e.u. ;this is due apparently to the resonance energy of the allylic cation rather than to nonbonded interactions. Halo- genium ions (13;Z = C1 Br I) have been prepared by ionisation of the fluoro- compounds (14),in SbF,-HF the stereochemistry has been shown to be that Me Me SbF -Me CH derived from rearside displacement of fluoride only for the iodidesz5 Both threo-and erythro-(15; Z = C1 or Br) lead to the same mixtures of cis-and trans-halogenium ions.24 Evidently the cyclic ion is in equilibrium with an open carbonium form in which rotation can occur. The 1,l-dimethyl-2- chloroethyl cation is more stable than the corresponding chloronium ion form from which the n.m.r.spectrum readily distinguishes it. Five- and six- + threo or Erythro (15) cis + trans (16) membered halogenium compounds (16) have also been recognized and can be formed by dissolution of the 1,6-dihalogenohexane or 5-halogenohex-1 -ene in SbF5-HS03F at low temperatures.26 A variety of hydroxycarbonium ions have now been shown to be stable in these strong acid solutions. Carboxylic 24 G. A. Olah J. M. Bollinger and J. Brinich J. Amer. Chem. Soc. 1968,90,2587 25 G. A. Olah and J. M. Bollinger J. Amer. Chem. SOC.,1968,90,947. 26 G. A. Olah and P. E. Peterson,J. Amer. Chem. SOC..1968,90,4675. Reaction Mechanisms 107 acids,27 dialkyl carbonates and hydrogen carbonates2* protonate to give (17) and (18) respectively ; protonated carbonic acid (trihydroxycarbonium OR' 4,-R3-C:.+ \-OR' (17) R' = RZ = H (19) X = Y = Z = OH SH NHZ (18) R' = R3.R' = H X = Y = OH,Z = SH,NH' R' = RZ = R3 X = OH,Y = Z = SH,NH (20) X = OH;Y,Z =OH,OR ion) is stable to 0". The complete series of sulphur and nitrogen analogues have also been observed2' (19) (formed from thiocarbonic and carbamic acids urea and guanidine). Hydrogen cyanide and aliphatic nitriles protonate on nitrogen3' but carbamates protonate on oxygen (20). It is of great interest to observe such species many of which are implicated in acid-catalysed hydrolyses as transient intermediates. Dialkoxycarbonium ions (isolable as the tetrafluoroborates) behave as oxygen analogues of the ally1 cation and show a considerable rotation barrier about the C-0 bonds (21).31 At -30" R' I I I R' (21) RZ the alkyl groups R2 are distinguishable pointing to a preferred configuration but the separate signals collapse to a single one above 0" when rapid rotation brings both groups into a time-averaged identical environment.Protonation of methane to CHZ has been suggested to account for the isotopic exchange which takes place between CD and SbF,-HSO,F although an alternative route via the methyl cation might also be considered parallel to the behaviour of ethane. At higher temperatures (80-140") telomerisation of methane to t-butyl and di-isopropylmethyl cations occurs. 32 In superacid solutions diketones give rise to the bis-carboxonium ions3 (22) while at low temperatures diprotonated glycols can be observed and *' (a) G.A. Olah and A M. White J. Amer. Chem SOC.,1967,89 7072; (b)G. A. Olah and M. Calin J. Amer. Chem. SOC. 1968,90,405. 28 G. A. Olah and A. M. White J. Amer. Chem. SOC.,1968,90,1884. 29 G. A. Olah and A. M. White J. Amer. Chem SOC.,1968,90,6087. 30 (a) G. A. Olah and T. E. Kiovsky J. Amer. Chem. SOC. 1968 90 4666; G. A. Olah and M. Calin ibid. p. 4672; (b)G. A. Olah and M. Calin J. Amer. Chem. SOC.,1968,90,401. " R. F. Borch J. Amer. Chem. SOC.,1%8,90,5303. 32 G. A. Olah and R. Schlosberg,J. Amer. Chem. SOC.,1958,90,2726. 33 D. M. kouwer Rec. Trav. chim. 1968,87,225. 108 N. S. Isaacs undergo pinacolic rearrangements at higher temperatures.34 35 Brouwer has observed the n.m.r. spectra of some hydroxyallyl cations e.g. (24).36A temperature-dependent study of the n.m.r. spectrum of the t-pentyl cation37 has revealed the occurrence of Wagner-Meerwein rearrangements of methyl groups and hydride ions which retain their integrity throughout (25). Hexa-1,5-diene is converted to the methylcyclopentyl cation. 38 Further studies of benzenonium ions have included the crystal structure of heptamethylbenzenonium tetrachloroaluminate (26),39which shows bond lengths fairly close to those predicted from simple HMO theory (26 ;bracketed figures). Fluorot oluenes protonate in superacid media to give methylfluoro- Me \+ C-CH,-Me/Me Me\ ++ Me-C-CH-Me H / \/+ C-C-Me H’ \Me HMe + .+MeCH,-C Me + Me / \ (25) 1.536 1-497-,MeMe> 1.489 H H I7 (27) -Hf(40%) +0.092 +0.01 9 (281 benzenonium ions.“ Brouwer has observed and analysed the mixtures of isomeric benzenonium ions4’ produced by protonation at different sites in halogenotoluenes [e.g.(27)l. The same author has studied the kinetics of methyl migration among methylated benzenes in SbF,-HF by direct n.m.r. spectral observation^.^^ The 1,2-and 1,4-dimethylbenzenonium ions are transformed into the corresponding I,3-dimethyl ions at unimolecular rates of80 and 335 set.-at 25 ; 1.2.3,4-tetramethylbenzenoniumion gives 1.2.3.5- 34 G. A. Olah and J. Sommer J. Amer. Chem. Soc. 1968,90,927. ” G. A. Olah and J. Sommer J. Amer. Chem. Soc. 1968,90,4323. 36 D. M. Brouwer Tetrahedron Letters 1968,453.37 M. Saunders and E. L. Hagen J. Amer. Chem. SOC.,1968,90,2436. 38 D. M. Brouwer Rec. Trav. chim. 1968,87,702. 39 N. C. Baenziger and A. D. Nelson J. Amer. Chem. Soc. 1968,90,6602. 40 G. A. Olah and T. E. Kiovsky J. Amer. Chem. SOC.,1968,90,2583. 41 D. M. Brouwer Rec. Trav. chim. 1968,87,335. 42 D. M. Brouwer Rec. Trac. chim. 1968,87 611. Reaction Mechanisms 109 (155 sec ') and 1,2,3-trimethylbenzenoniumion is slowly converted to 1,2,4- trimethyl (8-9 sec ') and very slowly in turn into 1,3,5-trimethyl (lo-' sec '). Enthalpies and entropies of activation are in the range 19-23 kcal. mole-' and ca. -3 e.u. respectively. It will be of interest to compare these values with computed stabilities of the benzenonium ions. From l3C-n.m.r. data the charge- densities on each carbon of the 2,4,6-trimethylbenzenoniumand trityl cations have been measured and have been compared with theoretical values obtained by simple HMO and by SCF theories (28).43*44The superiority of the latter values are evident but still tend to exaggerate the values.CNDO (Complete Neglect of Differential Overlap) calculations on some simple carbonium ions have been reported and give a plausible account of the geometries and charge distributions although energies are not well reprod~ced.~' Reasonable agreement with experimental ionization potentials has been obtained by an SCF technique and calculated electronic structures of carbonium ions and protonated hydrocarbons have been reported.46 Calorimetric determination of the heats of formation of benzenonium ions has shown that their stabilities increase with increasing alkyl s~bstitution~~ as predicted.The pentamethylbenzenonium ion has been observed to be formed from the pentamethylcyclopentadienylmethylcation in FS03H (29a) rearranges to (29b) which undergoes a degenerate scrambling of the ring carbons.48 Transient Carbonium Ions.-Methods used for the generation of carbonium ions have included the oxidation of radicals by and the transfer of NO; from tetranitromethane to an olefin. The decomposition of N-nitroso- (or N-nitro-)-N-alkylamides and carbamates (30) gives rise to alkyl carbonium ions recognizable from the products5'* 52 of their subsequent reactions. The 43 G. J. Ray A. K. Colter D. G. Davies D. E.Wisnosky and R J. Kurland Chem Comm. 1968 815. 44 V. Koptyug A. Rezvukhin E. Lippmaa and T. Pehk Tetrahedron Letters 1968 4009. " K. Wiberg J. Amer. Chem. SOC.,1968,90,59. 46 T. Youezawa H. Nakatsuji and H. Kato J. Amer. Chem. SOC.,1968,90 1239. 47 E. M. Arnett and J. W. Larsen J. Amer. Chem. SOC.,1968,90 791 792. 48 R F. Childs M. Sakai and S. Winstein J. Amer. Chem SOC. 1968 90 7146; R F. Childs and S. Winstein J. Amer. Chem. SOC.,1968,90 7146. 49 (a) J. K. Kochi and A. Bemis .I.Amer. Chem. SOC. 1968,90 4038; (b) A. B. Evnin and A. Y. Lam Chem. Comm. 1968,1184. 50 S. Penczek J. Jagur-Grodzinski and M. Sczwarc J. Amer. Chem. SOC. 1968,90,2174. 51 E. H. White H. P. Tiwari and M. J. Todd J. Amer. Chem. SOC. 1968,90,4734. 52 E. R. Stedronsky J. Gal.R. A. M. O'Ferrall and S. I. Miller J. Amer. Chern. SOC.,1968.90.993. 110 N. S. Isaacs N2NHAr / Ar C=C -H+ Ar,C=&Ar ‘Ar + N2+ ArNH2 (31) (32) anodic oxidation of radicals (the ‘abnormal’ Kolbe reaction from carboxylate ions) has been used to generate the pinacolyl cation53 and the neopentyl cation.54 In both cases a mixture of rearranged and unrearranged products was obtained. Triaryltriazenes (3 1) undergo acid-catalysed cleavage to vinyl cations (32).55 A primary vinyl cation is also formed by addition of the ada- mantyl cation to a~etylene.’~ It rearranges to the (presumably) more stable secondary vinyl cation by a hydride shift the products on hydrolysis being acetyladamantane and adamantylacetaldehyde. A good correlation was observed between solvolytic rates of formation of benzylic cations in the polynuclear hydrocarbon series and changes in the Huckel x-energies from which may be deduced a resemblance between the transition state for the reaction and the carbonium ion.57 Arylsilylcarbonium ions have been generated e.g. (33); silicon appears to be less ready totransfer aphenyl group thandoescar- bon but the reaction can be achieved.58* ’’It is possible that greater stabilisation f Ar,Si-CHAr R$iH + Ri6 + R$i+ + RiCH (33) (34) of the positive charge occurs when adjacent to the silicon atom thus permitting back-donation through d-orbital participation. This however cannot mean that carbonium ions are more stable than their silicon analogues since trityl cations are readily reduced by triarylsilanes and silyl cations are formed (34).6o The solvolysis of ferrocenylethyl acetates bearing substituents in the second cyclopentadienide ring (35) shows a general correlation of rates with q,,or 0,values (rather a better one with the combination (om+ op/3))and a 103-fold difference in rates between (35; R = Me) and (35; R = CN).6’ It is clear that substituent effects are transmitted interannularly in the ferrocenyl Fe 53 P.S. Skell and P. H. Reichenbacher J. Amer. Chem. SOC.,1968,90,3436. 54 P. S.Skell and P. H. Reichenbacher J. Amer. Chem. SOC.,1968,90,2309. 55 F.W. Miller Diss. Abs. 1967 BB 1857. 56 T. Sasaki S. Eguchi and T. Toru Chem. Comm. 1968 780. 57 G.J. Gleicher J. Amer. Chem. SOC.,1968,90 3397.58 K.H.Pannell Diss.Abs. 1968,BB 4505. 59 A. G.Brook K. H. Pannell and D. G. Anderson J. Amer. Chem. SOC.,1968,90,4374. 6o F.A.Carey and H. S. Tremper J. Amer. Chem. SOC.,1968,90,2578. 61 D.W.Hall E. A. Hill and J. H. Richards J. Amer. Chem. SOC.,1968,90,4972. Reaction Mechanisms 111 system but the mechanism by which this occurs is not certain. The acid-catalysed hydrolysis of vinyl ethers,62 which occurs much more readily than with the saturated analogues proceeds via the oxocarbonium ions (36); the stability of these ions and hence rate of formation falls in the order R' R2 = H > R' = H R2 = Me > R1,R2= Me. The ease of formation of highly branched tertiary carbonium ions increases very rapidly as the relief of steric strain becomes increasingly important (37a-e).6 Rearranged products were not +PNB $\PNI3 krcl 1 13,000 19,000 68,000 560 PNB = -0.C O O NOz obtained and alkyl participation seems to be unimportant. However a high degree of configurational retention was observed in the deamination of [l *HI neopentylamine to account for which methyl participation has been The formation of the alkyl-migration product (in ca. 3% yield) during the deamination of (38) is claimed65 to be due to the rather unfavourable 0 geometry for the preferred phenyl migration which indeed occurs to give the large majority of products; the plane of the ring is inclined however at ca. + 60"to the C(a)-CH bond instead of the 90"usually assumed most favourable. The result is suggestive but needs more definitive evidence to support this interpretation.Ion-pair return in the acetolysis of arylsulphonates has been 62 T. Okuyama T. Fueno T. Nakatsuji and J. Furukawa J. Amer. Chem. SOC.,1967,89,5826. 63 P. D. Bartlett and T. T. Tidwell J. Amer. Chem. SOC., 1968,90,4421. 64 R. D. Guthrie,J. Amer. Chem. SOC. 1967,89,6718. 65 W. E. Parkham and L. J. Czuba J. Amer. Chem. SOC.,1968.90.4030. 112 N. S. Isaacs studied using '*O-labelled substrates.66 The label originally placed specific- ally accumulates in the singly bound oxygen due to return from the symmetrical sulphonate ion (39) at a rate amounting to 5-100/ of the acetolysis rate. 18 0 +1 R 1 .,\ -':S-ORz ,;/ co+ 6o (39) (40) (4 1) Bridgehead acyl cations such as (40) are more stable towards decarbonylation than those which may give rise to a planar carbonium In such cases acylated products may be obtained.The carbonium ions produced from cis-and trans-9-chlorodecalins and from 4-cyclohex-1 -enylbutyl toluene-p- sulphonate are apparently different as judged from the different proportions of produ~ts-A'(~)- and A'-octalins and cis-and trans-decal-9-01s-which are cbtained on hydrolysis under otherwise identical conditions.68 The results suggest that the presumed common intermediate the 9-decalyl cation (41) or an ion-pair exists as different conformers or in different solvation states although alternative explanations could include the incursion of different amounts of bimolecular substitution and elimination reactions and in the latter case 71-assistance.The cyclohexyl cation generated by the reaction between the acetyl cation and cyclohexane rearranges to the more stable methylcyclopentyl cation from which the majority of the products are derived.69 The solvolyses of 4,4'-disubstituted benzhydryl halides were observed to show (42) 66 A. F. Diaz I. Lazdins and S. Winstein J. Amer. Chem. SOC.,1968,90 1904. 67 D. G. Pratt and E. Rothstein J. Chem. SOC.(C),1968 2548. A. F. Boschung M. Giesel and C. A. Grob Tetrahedron Letters 1968 5169. 6q 1. Tabushi. K. Fujita and R. Oda Tetrahedron Letters. 1968.4247. Reaction Mechanisms rather poor obedience to the additivity rule of substituent effects.70 A thorough survey of the products of solvolysis of some classical secondary carbon- ium ions (4-octyl 4-t-butylcyclohexyl and 2-decalyl) has been published.' Products derived by an initial hydride shift are shown to be significant and provide a clearer insight into the fate of these ions i~ a variety of solvent. The ease of ionisation of bridgehead halogen substituents in bicyclic systems appears to be governed by the amount of steric strain which the carbonium ion can accommodate. A good linear plot was obtained relating calculated strain differences between halide and cation with log k for the systems (42a- f).72-74Relief of ring-strain is apparently responsible for the great enhance- ment of solvolytic rates of bicyclo[2,2,0]hexylmethyl p-nitrobenzoate (43) (to form bicyclo[2,2,l]heptyl derivative^)^^ compared with the neopentyl (44):X =-OCO.C,H,.CH compound.A factor of 7 x lo6 was recorded. A good correlation between rates of solvolysis and strain-energy release was found for six l-bicycloalkyl- methyl compounds (43,Ua-e). Changes in strain energy in forming a trigonal carbon may be implicated in the ob~ervation~~ that (45) solvolyses some 6.5 times more rapidly than (46) but the fact that the isomer (47) reacts some ten times more readily than (45) suggests that perhaps the relief of 1,3-diaxial 'O E. Berliner and M. Q. Malter J. Org. Chem. 1968,33,2595. N. C. G. Campbell D. M. Muir R R Hill J. H. Parish R M. Southam and M. C. Whiting J. Chem. SOC.(B),1968 355. 72 P. v. R. Schleyer P. R. Isele and R. C. Bingham J. Org. Chem. 1968,33 1239.73 W. G. Dauben and C. D. Poulter J. Org. Chem. 1968,33 1237. 74 W. G. Dauben J. L. Chitwood and K. V. Sherer J. Amer. Chem. SOC.,1968,90 1014. 75 C. W. Jefford D. T. Hill and J. Gunsher J. Amer. Chem. SOC. 1967,89,6881. 114 N. S. Isaacs interactions may be more important. Curiously the ratio of exo-to endo-reactivities is the reverse of that found in the 2-norbornyl system. (45) X = OTOS,Y= H (47) X = H Y = OTOS In the present case observed rates were not too dissimilar from values calculated by the Halford-Foote-Schleyer relations hi^^^ but as in all such studies more certain energetic relationships would be obtained by comparison of free energies of activation rather than relative rates. A combination of strain release and enhanced conjugation is probably responsible for the isomerisation of protonated he~amethyldewarbenzene~~ (48) to the hexa- methylbenzenonium ion in very strong acid medium.Two indirect pathways are postulated. A 1,3-hydrogen shift in (49) competes almost equally with 1,Zcarbon migration the products being (50)and (51)respectively.78 However at -78" in SbF,-HSO,F both hexamethyl Dewar benzene and hexamethyl- prismane protonate to a species with four distinct methyl groups in their n.m.r. spectrum which was identified as (51a).79 &-ax H / 76 C. S. Foote J. Amer. Chem. Soc. 1964,86 1853; P. von R. Schleyer ibid. pp. 1854 1856. 77 H. Hogeveen and H. C. Volger Rec. Trau. chim. 1968,87,385. 7B R. A. Appletoq J. C. Fairlie R. McCrindle and W.Parker J. Chem. SOC. (C) 1968 1716. 79 L. A. Paquette G. R Krow J. M. Bollinger and G. A. Olah J. Amer. Chem Soc. 1968 90 7 147. Reaction Mechanisms "on-Classical' Carbonium Ions and IT-Assisted Ionization.-Two contro-versial systems continue to stimulate a considerable volume of work namely derivatives of bicyclo[2,2 llheptane (norbornane) and cyclopropylmethyl cations. It has been long established that the cyclopropyl group together with other similarities to the ethylenic double bond acts as a carbonium ion stabilising group and carbon scrambling occurs between the ring- and exocyclic atoms. Extended Hiickel calculations" suggest that the classical cyclopropylmethyl structure (52) is more stable than the symmetrical nonclassical representation (53),but should readily undergo a degenerate rearrangement by a suprafacial methide migration via the bent cyclobutonium species (54)" The same authors support this hypothesis by studies on a rigid cyclopropylmethyl cation that is formed by solvolysis of 9,lO-dehydroadamantyl toluene-p- sulphonate (55).82 The reaction occurs faster than that of adamantyl toluene-p- sulphonate by a factor of 5 x 10' and deuterium initially in position 2 is distributed equally in positions 2 9 and 10 in the products.The scheme (55) -+(56) is consistent with the facts. Wiberg and S~iemies*~ have attempted to distinguish between mechanisms for the cyclopropylmethyl rearrangement by a stereochemical argument. Rearrangement of an unsymmetrically sub- stituted ion such as (57) could occur by overlap of the vacant p-orbital with either the interior or exterior lobes of the opposite o-bond with different stereochemical consequences [(58) and (59)].The product (59) also be formed by transformation through a bent cyclobutonium ion but a mixture of (58) and (59) would result from a planar cyclobutonium ion.The hypothesis was examined by analysis of the products of acetolysis of bicyclobutane in acetic 8o L. C. Allen and J. D. Russell J. Chem. Phys. 1967,46 1029 (ref. 81 J. E. Baldwin and W. D. Fogelsong J. Amer. Chem. SOC.,1968,90,4311. '* J. E. Baldwin and W. D. Fogelsong J. Amer. Chem. SOC.,1968,90,4303. 83 K.B. Wiberg and G. Szeimies J. Amer. Chem. SOC.,1968,90,4195. 116 N. S.Isaacs 1+3% (60) [2H]acid when the product cyclopropylmethyl acetate had the isotopic composition denoted in (60).Almost all the deuterium is found in the carbinyl and trans-2-positions which indicates that the cyclopropylmethyl-cyclo-propylmethyl rearrangement is occurring and the specificity of this labelling must result from the regeneration of the same labelling pattern at each re- arrangement either by process (59b) or via the nonplanar cyclobutonium ion.The solvolytic fate of the cation (61) has been interpreted as follows.84 It was found that the product (62) contained no deuterium in the vinylic positions from which the initial shift was deduced to lead to a cyclopropylethyl-type (63) of ion which then rearranges to the presumably more stable cyclopropyl- methyl type (64).It seems curious that this is not produced initially although possibly the answer lies in the relative bond strengths of the C(lkC(7) and C(4)-C(7) bonds. Some sort of interaction between a cyclopropane ring and a + & (6 1) OAc (62) OBs Kos' -+ bAC AcOH (65) (653) (66) (67) 84 J. M. Berson G. M. Clarke. D. Wege. and R.G. Bergrnan. J Amer. Chem. SOC.. 1968.90 3238. Reaction Mechanisms P-carbonium ion centre may be inferred from the enhanced reactivity of (65a) compared to (65).85 A factor of only ten is involved but racemisation of (65a) is four times faster than solvolysis which leads to rearranged products (66) and (67). The cyclopropane ring in 2-bicyclo[ 3,1,0] hexyl chloride (68) brings a rate enhancement by a factor of lo4compared to cyclopentyl chloride which seems too large to ascribe to steric factors.86 It would be interesting to examine possible scrambling of the carbons in the five-membered ring during this reaction.Triarylbicyclo[3,1,0] hexan-3-01s ionise in concentrated sulphuric acid or in the presence of Lewis acids to give coloured species8' (hmax -500nm.) clearly not due to simple benzyl cations but possibly trishomocyclopropenyl cations (69).Further information on these interesting species would be welcome for instance from the n.m.r. equivalence or nonequivalence of the methylene protons and by observation of migration of the hydroxyl-group after hydrolysis. However only very slight rate enhancement was noted for the hydrolysis of 2-cyclopropylethyl p-bromobenzenesulphonate compared with the ring- opened analogue whereas in the 7-norbornyl series a 103-fold rate increase is brought about by the endo,anti-cyclopropano-group.88* 89 There are many observations which are still poorly understood concerning these systems.A method for obtaining estimates of relative lifetimes of carbonium ions employs their generation from the diazotate (70) in *O-enriched water. Short-lived ions tend to capture the diazotate oxygen (l60)by internal return. while longer-lived species are assumed to react more with water to give a labelled alcohol (71). From such studies the cyclopropylcarbonium ion appears to have a longer lifetime than the 2-octyl cation." Two neighbouring spiro- cyclopropane rings are highly effective in promoting ionization although not 'CH \ (7 O) OTos n = 2,3,4 (72) 85 J.A. Berson D. Wege G. M. Clarke and R G. Bergman J. Amer. Chem. SOC. 1968,90,3240. 86 P. R. Brook R. M. Ellam and A. S. Bloss Chem. Comm. 1968,425. 87 W. Broser and D. Rahn Chem. Ber. 1967,100,3472. 88 M.J. S. Dewar and J. M. Harris J. Amer. Chem. SOC.,1968,90,4468. 89 Y. E. Rhodes and T. Takino J. Amer. Chem. SOC.,1968,90,4469. 90 R. A. Moss F. C. Shulman. and E. Emery J. Amer. Chem. SOC..1968,90,2731. 118 N. S. Isaacs as effective as when the cyclopropane rings are fused and occupy a more coplanar situation relative to the vacant p-orbital of the carbonium ion.g' Related studies show that a major factor which governs solvoly$ic rates in the spiran series (72) is the ring strain imposed in generating the carbonium 93 The series of exo-bicyclo[n,l,O]alkylmethyl toluene-p-sulphonates (n = 1-7) has been prepared and their solvolytic reactivities have been mea~ured.~~,~~* 96 A sharp maximum in rate appears for the n = 4 compound and the authors interpret the reactions as going initially through a cyclo-propylmethyl cation after which numerous rearrangements occur.No assist- ance to ionisation was evident in the compound (73) which could be ascribed to the three-membered ring." The compound (74) was designed as an example in which reversible heterolysis to (75) might occur in a polar solvent. It was (CH ) OTos Me ?;?r"02ph MASO,Ph= Me COzMe Me CO Me observed that the rate of racemization exceeded the rate of solvolysis in metha- mol at 150" by a factor of 9 which was interpreted as evidence for the dipolar intermediate (75).98 It was noticed that," of the four stereoisomeric bicyclo- [4,2,0]octyl toluene-p-sulphonates two the cis,exo-(76) and the trans,exo- (77)give single product types on acetolysis.It was postulated that the rearrange- ments of cyclobutyl cations are subject to orbital symmetry control and in these cases are further limited by steric factors. The trans-cyclo-octenol produced from (77) was trapped as its adduct with phenyl azide. 91 P. Krapcho R. C. H. Peters and J-M.Conia Tetrahedron Letters 1968 4827. 92 D. Applequist and W. A. Bernett Tetrahedron Letters 1968 3005. 93 K. W. Wiberg and J.E. Hiatt Tetrahedron Letters 1968 3009. 94 A. J. Ashe Diss.Abs. 1967,27B 4298. 95 K. B. Wiberg and A. J. Ashe J. Amer. Chem. SOC.,1968,90,63. 96 P. v. Schleyer and G. W. Van Dine J. Amer. Chem. SOC.,1966,88,2321. 97 G. D. Sargent R. L. Taylor and W. H. Demisch Tetrahedron Letters 1968,2275. 98 D. J. Cram and A. Ratajczak J. Amer. Chem. SOC.,1968,90,2198. 99 K. B. Wiberg and J. G. Pfeiffer J. ,4mer. Chem. Soc.. 1968,90,5324. Reaction Mechanisms x Y X X ce Gpi I J. The norbornane system is still providing great scope for experimental work. It has been long known that startlingly large rate enhancements are observed in the 7-norbornyl series when double-bonds are placed in the 2,3- (anti) and 5,6-positions (78a-d). loo Explanations which have been put forward include x-participation either by way of a homoallylic (78e) or symmetrical non- classical ions (780 and steric considerations in particular the widening of the C(l)-C(7)-C(4) angle whose constraint in (78a) is primarily responsible for its greatly depressed solvolytic activity.Since major structural changes bring about alterations in both steric and electronic factors recent work has con- centrated on systems in which independent control of the variables could be realised. A search for 'bridge-flipping' (79) in the norbornadienyl cation has revealed by the n.m.r. spectrum of this stable cation that such a rearrangement does not occur rapidly at -78" in fluorosulphonic acid."' Two separate kinds of vinyl protons are observed a 'bound' pair resonating at z 2.54 considered due to a bishomocyclopropenium system and a 'free' pair at z 3.90 more nearly R R (7 9) (801 normal.The 7-hydrogen resonates at T 6.77 from which it appears that a great deal of positive charges has been removed from the 7-carbon atom (compare the %hydrogen in the 2-propyl cation at T -3-5).At higher tempera- loo H. Tanida Accoultts Chem. Res. 1968,1,239. lo' R. K. Lustgarten M. Brookhart and S. Winstein J. Amer. Chem. Soc. 1967,89 6350. 120 N. S. Isaacs tures the two types of vinyl proton do not merge but a degenerate rearrangement sets in as shown by deuterium-labelling experiments. Scrambling of deuterium from the unbound vinyl position to all carbons except the bound vinyl is observed at -47" (80).It is possible that bridge flipping occurs at higher temperatures but a lower limit of 19.5 kcal. mole-' is estimated for the activa- tion energy. 7-Methylnorbornadienyl however,lo2 exhibits two types of vinyl signal at low temperatures which coalesce above -14" while the methyl signal remains sharp. This is interpreted as due to the equilibrium (79; R = Me) (AF* = 12-4 kcal. mole-') while 7-phenylnorbornadienyl (79; R = Ph) is rapidly interchanging even at -70" '03 giving an upper limit of AF* for the equilibrium of 7.6 kcal. mole- '. It is much less easy to obtain definite evidence for the existence of o-participation in the solvolysis of 7-norbornyl deriva- tives. Miles'04 has shown that predominant retention of configuration in the solvolysis of the isotopically labelled compound (8 1) occurs.The configura- tion-holding effect could conceivably arise from o-participation or from a front-side solvent interaction such as (81b). These results have been confirmed by other workers'05 who have also isolated a small (ca.3 %) amount of bicyclo- [3,2,0]heptyl acetate which was shown to consist of the isomers (82) and (83) in the ratio of 20 :1. The former can arise from a rearside 1,Zshift on the intimate ion-pair (81b) but the latter requiring a frontside 1,Zshift is unlikely to be derived immediately from (81 b) for steric reasons. Considering the small amount of (83) formed however it seems unnecessary to abandon the ion-pair intermediate entirely but for the formation of the major product some special configuration-retaining situation occurs.The energetics of the epimerisation of the bicyclo[2,2,l]heptan-2-ols (84) have been studied both from the view- point of racemisation and isomerisation rates. '07 The difference in activa- tion enthalpy for formation of the intermediate ion from either epimer (AH2-AHl) amounts to 4.3 kcal. mole-' for R = H but 7.8 kcal. mole-' for R = Me. The authors interpret this greater reactivity of (84) R = H as due to a contribu- tion from o-participation whereas the methyl analogue (84); R = Me) is supposed to ionise to an essentially classical tertiary carbonium ion. An '02 M. Brookhart R. K. Lustgarten and S. Winstein J. Amer. Chem. SOC. 1967,89,6352. M. Brookhart R. K. Lustgarten and S. Winstein J.Amer. Chem. SOC.,1967,89,6354. lo4 F. B. Miles J. Amer. Chem. SOC.,1968,90 1265. lo5 P. G. Gassman J. M. Hornback and J. L. Marshall J. Amer. Chem. SOC.,1968,90,6238. lo6 H. Goering and K. Humski J. Amer. Chem. SOC.,1968,90,6213 lo' H. L. Goering C. Brown and C. B. Schwene J. Amer. Chem. SOC.,1968,90,6214. Reaction Mechanisms alternative interpretation of this work views solvolyses of the exo-compounds as being normal whilst the endo-isomers as retarded by a steric factor,Io8 a further example of the dichotomy of viewpoint regarding nonclassical car- R (84) a; K = H OPNB b R =Me (85) (86) bonium ions. Steric hindrance to ionisation as an explanation of these rate differences has also been stressedlog on the grounds that high exo :endo rate ratios are also observed in the compounds (85) and (86) where similar steric environments of each isomer are found to the corresponding ones in the nor- bornyl series but a suitable situation for o-participation is absent.Interesting studies were reported concerning substituent effects in benzonorbornenes. The solvolyses of 6(7)-substituted benzonorbornene-anti-9-brosylatesshow great dependence on the electronic nature of the substituent.”’ A Hammett plot is linear with p = -4-8 [based on substituent effects assessed as gop+ op’)] or -5.1 [based on ~op’+ a,‘)],an extremely large dependence on electron availability. This may be emphasised by comparison of the rates for extreme cases (Z = OMe and Z = NOz) for the benzonorbornyl system (87) and the 3,4-benzocyclopentane system (88).In the former case koMe/kN02= 368,000 and in the latter 8. Less clear is the mechanism of participation of the aromatic ring in the reactions of 5-substituted benzo-2-norbornenes (89). Here the exo:endo rate ratio is lo4 and the introduction of methoxy-groups has very little effect from any position with the exception of the 6 (‘homo-para’) where a rather large enhancement is observed for the exo-isomer. The nonclassical view of this effect would regard the cation formed (90), as being ‘homobenzilic’. Y + lo’ H. C. Brown and M. Rei J. Amer. Chem. SOC. 1968,90,6216. lo9 H. C. Brown. I. Rothberg and D. L. Van der Jagt J. Amer. Chem. Soc. 1967,89.6380 122 N. S. Isaacs These results have been confirmed qualitatively but with somewhat different values for the relative rates.110-113 .As anticipated the 6-nitro-derivative is deactivating the em :endo rate ratio dropping to 10'. These effects have been treated theoretically by the method of bond superdelocalisabilities and general agreement with experimental values has been reported. 'I4 Even when the reaction centre is removed by a further two carbons (91) similar though attenuated effects are observed.'15 The syn:anti rate ratio drops to 20 and kMeO/kNO2= 150 for syn-compounds but zero for the anti-isomers. Such effects could result from conformations such as (91) and the interaction be- tween aromatic ring and positive centre amount to a charge-transfer interac- tion. Dewar has reported the existence of such charge-transfer com-plexes from spectroscopic evidence.A p-methoxyphenyl group on the same carbon atom as the leaving group. (92). satisfies the electronic demands of the ionisation such that a-participation (in the norbornyl system) and even x-participation (in exo-norbornenyl) is redundant .' 16* 'I7 The I OMe (93) (92) decarbonylation of (93) (forming tropilidine) is greatly facilitated by an endo- cyclopropane ring compared to the em while the benzo-analogue is very resistant to decarbonylation on account of the loss of aromaticity which this entails.'18 The system (94) exhibits what is probably the largest driving force H. Tanida T. Tsugi and S. Terataki J. Org. Chem. 1967,32,4121. '" D. V. Braddon G. A. Wiley J. Dirlam and S.Winstein J. Amer. Chem. SOC.,1968,90 1901. H. Tanida H. Ishitobi and T. Irie J. Amer. Chem. SOC.,1968,90,2688. H. C. Brown and G. L. Tritle,J. Amer. Chem. SOC.,1968,90,2689. 'l4 H. Tanida and T. Tsushima J. Chem. SOC.(Japan),1968,89,14. R. Muneyaki and H. Tanida J. Amer. Chem. SOC. 1968,90,656. '" H. C. Brown and K. Takeuchi,J. Amer. Chem. SOC. 1968,90,2691. 'I' P. G. Gassman J. Zeller and J. T. Lumb. Chem. Comm.. 1968. 69. Reaction Mechanisms to ionisation yet discovered."* The effect may be described in terms of a nonclassical ion (93 and perhaps as a n-butressing effect. The compound (96) is also extraordinarily reactive. A related subject of great interest at present is the identification of homoallylic and more distant n-participation.Homoallenyl systems seem to be considerably more reactive than homoallylic which in turn are more reactive than the saturated analogues (97a-c).' 19,I2O However the optically active allenic compound (98) in a polar medium undergoes racemization and also ring closure to the cyclopropane (99). It seems likely that the former originates by dissociation of (98) to a classical car- bonium ion followed by return of the anion while the latter involves rearside attack on the asymmetric carbon atom by the n-electrons thus retaining optical activity. An impressive demonstration of the involvement of at least three carbons of a homoallylic system is provided by the nucleophilic sub- stitutions with homoallylic rearrangement of (100) and its enantiomer which Ac Me 118 (a)B.Halton M. A. Battiste R Rehberg C. L. Deyrup and M. E. Brennan J. Amer. Chem. SOC. 1967,89 5964; (b)E. L. Allred and J. C. Hinshaw Tetrahedron Letters 1968 1293. T. L. Jacobs and R Macomber Tetrahedron Letters 1967,4877. '*' R. T. Swindell Diss Abs. 1967,28B 120. 124 N. S. Isaacs proceed in a completely stereospecific manner12 (ie. C~S-CCH, cyclopropyl-H -+ cis-olefins and also the reverse reaction. The reaction has potential pre- parative value. Stereospecific double homoallylic ring-expansions were also reported,'22 e.g. (101). OTos 101 The formation of 2-cyclopropyltetrahydrofuran (102) by the action of silver on 7-iodohept-4-en01 is suggested as having occurred by the internal trapping of a homoallylic cation (103)'24 and a similar interpretation may be put on the reaction (104) which proceeds with retention of optical activity,'25 although an alternative interpretation with good precedent involves rearside attack on the episulphonium ion (105).f-7 f +ArScl D-0 >-\7c + SAr (102) SAr Further information on the nature of the phenethyl cation of phenonium ion formed in the solvolysis of P-arylethyl toluene-p-sulphonates has been sought by Bentley and Dewar.'26 They argue that the rate of formation of the n-complex representation (106) should correlate with the n-energy dif- ference between ArH and (106) which is isoconjugate with ArCH; ;the rate of formation of the phenonium ion representation (107) however should correlate with the n-energy difference between ArH and the benzenonium ion (pentadienyl cation).A moderate correlation between log k for solvolysis and the nonbonding orbital coefficient for the benzyl cation is held to support 12' M. Bertrand and M. Santelli Chem Comm. 1968 718. 122 M. Gasic D. Whalen B. Johnson and S. Winstein J. Amer. Chem. SOC.,1967,89,6382. 123 D. Whalen M. Gasic B. Johnson H. Jones and S. Winstein J. Amer. Chem. SOC.,1967 89 6384. 124 L. A. Paquette and R. W. Begland J. Amer. Chem. SOC.,1968,90,5159. 125 T. L. Jacobs R. Macomber and D. Zunker J. Amer. Chem. SOC.,1967,89,7001. M. D. Bentley and M. J. S. Dewar J. Amer. Chem. SOC..1968,90. 1075. 125 Reaction Mechanisms (10 8) the former postulate a positive slope confirming the assistance towards ionization of the aryl group.On this latter point an observation by Cram and Thomson is re1e~ent.l~’ The solvolysis products of both erythro-and threo-(108; Z = H) have a largely retained configuration but inversion occurs for (108; Z = NO2).It is suggested that phenyl-assisted ionisation (accompanied by retention) can no longer be supported by the p-nitrophenyl group. It has been shown that the intermediate carbonium ion if indeed the reaction pro- ceeds via a carbonium ion produced from the tricyclyl toluene-p-sulphonate (109) is unsymmetrical and leads to products of retained configuration.128 Intermediates such as (1 10)are therefore ruled out and a plausible mechanism seems to be a nucleophilic attack at C-3 more or less concerted with ring- enlargement the driving force for this reaction over a straightforward attack at the primary carbon being the release of steric strain.However in a somewhat similar situation the intermediate cation or transition state appears to be symmetrical as judged by the loss of optical activity on solvolysis of (111). A possible structure is suggested as being (ll2).I2’ A new type of fluxional system (1 13) has been observed.130 0 II 0 / NHC Mes It o=c PhC[CH,],-Cl. 6”- (113 (1 14) (115) (1 16) 12’ D. J. Cram and J. A. Thompson J. Amer. Chem. SOC. 1967,89,6766. 12’ J. A. Berson R G. Bergman G. M. Clarke and D. Wege J. Amer. Chem. SOC. 1968,90 3236. lZ9 H. J. Goering and G. N. Fickes J. Amer. Chem. SOC. 1968,90,2848,2856,2862. M. J. Goldstein and B.G. Odell J. Amer. Chem. SOC.,89 1967,6356. 126 N. S. Isaacs Participation by Unshared Pairs.-Considerable interest in neighbouring- group participation by the carbonyl group has been shown. Thus the displace- ment of halide from the compounds (114;n = 1-5) shows a sharp rate maximum at n = 4 (a 700-fold enhancement over the phenacyl compound) due to (C=O; 5) participation the product in this case being a tetrahydrofuran.13' In the hydrolysis of aspirin esters general intramolecular acid catalysis by the ortho-carboxylic acid group and general intramolecular base catalysis by the carboxylate ion have been identified. '32-' 36 The acetamide group participates in the hydrolysis of the ester group in (115) as shown by the isolation of the intermediate imide (116) which hydrolyses to mesitoamide;' 37 similar effects are reported to occur' 38 in the hydrolysis of 2-acetamidoglycosides.N.m.r. line broadening has been used to detect amide participation in glycoside hydrolysis catalysed by lysozyme ;140 the following scheme was proposed (117). Ester participation in the hydrolysis of the 1 -phenethyl bromide derivatives (118) was inferred from the considerable ortho-effect kortho/kpora = 7.7. 14' enzyme Me H QC02Me X Y Z krd c1 c1 1 b; H CO2Ek CO2Et 2 c; c1 C1 H 1 d; CO2Et CO2Et H 120 Me z I 13' H. R. Ward and P. D. Sherman J. Amer. Chem. SOC.,1968,90,3812. lJZ A. R. Fersht and A. J. Kirby J. her. Chem. SOC.,1968,90 5818. '33 A. R. Fersht and A. J. Kirby J.Amer.Chem. SOC.,1968,90,5826. 134 A. R. Fersht and A. J. Kirby J. Amer. Chem. SOC.,1968,90,5833. lJ5 T. St. Pierre and W. P. Jencks J. Amer. Chem. SOC.,1968,90,3817. 136 A. R. Fersht and A. J. Kirby J. Amer. Chem. SOC.,1967,89,5960 5961. 13' R. M. Topping and D. E. Tutt J. Chem. SOC.(B) 1967,1346. 13* D. Piszkiewicz and T. C. Bruice J. Amer. Chem. SOC.,1968,90,5844. lJ9 D. Piszkiewicz and T. C. Bruice J. Amer. Chem. SOC. 1967,89,6237. G. Lowe and G. Sheppard Chem. Comm. 1968 529. 14' M. J. Straws L. J. Andrews R M. Keefer and I. Horman J. Org. Chem. 1968,33,2194. Reaction Mechanisms This factor however is quite moderate compared to many participation effects and since strain release probably accounts for at least a part of it the mechanism is not unambiguous.In a similar fashion the acceleration of the hydrolysis of the benzyl bromides (119) by two neighbouring carbonyl groups is suggestive of nucleophilic assistance; it is however difficult to assess contri- butions from steric and electronic factors. 142 The racemization of the sulphoxide (120) appears to be assisted by a carboxyl f~ncti0n.l~~ With a variety of substituent groups at the bridgehead position em-2-bromo-norbornanes solvolyse with a wide range of rates; 1-methoxycarbonyl and acetyl groups are retarding while the amino-group and to a lesser extent the carboxylate anion are accelerating. 144 Competition between inductive retardation and anchi- BrI 0 II Fe ‘0 (122) D I H (125) (1 26) 14’ M. J. Strauss L.J. Andrews and R M. Keefer J. Amer. Chem. SOC. 1968,90 3473. 143 S. Allenmark and C-E. Hagberg Acta Chem. Scand. 1968,22 1461 1694. 128 N. S. Isaacs meric assistance is evident the latter being deduced as operating on the amino- substituted compound by the loss of ammonia (121). Thus an ethyleniminium ion (121a) is not involved. Other interesting examples of neighbouring group effects include the transfer of oxygen from nitrogen to carbon during the hydro- lysis of o-nitrobenzhydryl bromide (122) with an ortho:para rate ratio of 83 ;145 and the nucleophilic displacement of cyanide by neighbouring hydroxy- group in the ferrocenyl series (123). 14' The 2-paracyclophanyl group is apparently an efficient configuration-retaining group since the toluene-p- sulphonate (124) solvolyses with complete retention of configuration.147 A rearside interaction between the aromatic system and the vacant p-orbital of the cation may be responsible or the bulk of the substituent may both prevent rearside attack by a nucleophile and hinder rotation of the carbon-carbon bond. Neighbouring oxime groups are effective in the catalysis of phosphate ester hydrolysis. 14' Six-centre transition states in the elimination of hydrogen halide from but-2-enyl halides have been suggested (124a).14' No participation of methoxyl in the solvolysis of (125) was observed. 150One would suppose that for reasons of geometry the interaction of the syn-7-methoxyl-group would only be effective in the endo-series. Sulphamate esters hydrolyse with internal return of the 0-alkyl group to give the zwitterion (126).Alkyl exchange also occurs giving crossed products from mixed esters.15' Substitution at Saturated Carbon.-In a re-examination of the Hughes- Ingold' 52 relationship concerning steric and polar factors in the S,2 reaction it has been concluded153 that observed and calculated values of rates and acti- vation energies and entropies agree well for the exchange reaction between alkyl halides and tetraethylammonium bromide in dimethylformamide. The reagent is known to be a moderately strong electrolyte and counters criticism1 54 Me (4 (b) (4 (4 (127) 144 J. W. Wilt and W. J. Wagner J. Amer. Chem. SOC.,1968,90,6135. 145 A. D. Mease M.J. Strauss I. Horman L. .f. Andrews and R M.Keefer J. Amer. Chem SOC. 1968,90,1797. J. H. Peet and B. W. Rockett Chem. Comm. 1968 120. 14' F. L. Harris Diss.Abs. 1967,27B 4306. 14* C. N. Lieske J. W. Havanec G. M. Steinberg and P. Blumberg Chem. Comm. 1968 13. 149 C. J. Harding A. G. Loudon A. Maccoll P. G. Rodgers R A. Ross S. K. Won& J. Shapiro E. S. Swinbourne,V. R Stimson and P. J. Thomas Chem. Comm. 1967 1187. 150 P. G. Gassman and J. L. Marshall Tetrahedron Letters 1968 2433. 15' P. F. Ziegler and M. Orchin J. Org. Chem. 1968,33 443. P. B. D. De LaMare E. S. Hughes C. K. Ingold L. Fowden and J. D. H. Mackie J. Chem Soc. 1955,3200. lS3 D. Cook and A. J. Parker J. Chem. SOC.(B),1968 142. 154 S. Winstein S. G. Smith and D. Darwish Tetrahedron Letters 1959 24; S. Winstein L.G. Savedoff S. G. Smith I. D. R. Stevens and J. S. Gall ibid.. 1960 24. Reaction Mechanisms that previous tests of the theory were invalidated by the weak electrolyte nature of the reagent (lithium halide in acetone for example). A careful study of the hydrolysis of the allylic chlorides (127a-d) has yielded evidence from the detailed kinetic expressions and from the variation with temperature of AFf for a gradation of mechanisms ranging from SN1-like for the secondary chloride (127a) through mixed SN1-sN2 for (127b) and (127c) and to purely sN2 for compound (127d). 155 If carbonium-ion stabilities are responsible for this behaviour then second-order effects must be considered in (127b4). Competitive studies on the relative reactivities of hydroxide methoxide ethoxide and allyloxide ions towards displacement of halogen from n-butyl benzyl and trityl bromides have shown that hydroxide ion is a comparatively weak nucleophile.'s6 This is most pronounced with the primary halide and presumably sN2 reaction (relative rates for OH- OMe- OEt- OC3HF were 1 10,37,42) and least for trityl (1 1,2,7,2 respectively).However concentrations of the nucleophiles present were estimated from acidities of the solvent com- ponents (aqueous alcohol mixtures) and are doubtless approximate. Nucleo- philicities of some stabilised nitrogen anions have shown that sulphonamide ions are somewhat less reactive than methoxide and succinimide and phthal- imide ions more reactive in the reactions with methyl iodide.'56 The hydrolysis of t-butyl chloride in aqueous alcohol in the presence of added salts (LiBr and NaBr) up to 2~ in concentration shows complex effects not alone attributable to changes in the activity coefficients of the salts as measured independently.A non-uniformly increasing rate is characteristic of increasing lithium bromide concentration while sodium bromide causes an initial increase (up to IM) beyond which the rate is depressed.'57 Such studies high-light our lack of knowledge of reagent interaction with the medium and indicate the need for further research. The nitro-group of a-nitrobenzhydryl chloride unlike that in 1-methyl-2-nitroethyl chloride is not sufficiently electron-withdrawing to suppress ionisation in a polar solvent so the hydrolysis proceeds by an S,1 mechanism.The hydrolysis of chloromethyl methyl ether has been shown to be a unimolecular reaction by its kinetics and by a substantial secondary isotope effect (kH/kD= 1-24) for MeOCD,Cl characteristic of hydrogen attached to carbon whch is undergoing a change in hybridisation in the rate-determining step.159A remarkable study of the rates of reaction of methyl iodide with several series of amines has pointed to a balance between inductive effects and steric requirements in determining rates. Many of these reactions however are reported to be slower in methanol than in benzene even quaternizations such as between methyl iodide and triethylamine or tri-n-butylamine. This is attributed to a higher solvation energy of the amine than of the (polar) transition state but is clearly at variance with the results of for instance 15' L.J. Brubacher L. Treindl and R.E. Robertson,J. Amer. Chem. SOC.,1968,90,4611. lS6 W. Reeve and P. F. Aluotto Tetrahedron Letters 1968,2557. 15' J-Y. Conan and A. Nattaghe Bull. SOC.chim. France 1968 1177. D. G. Norten and C. D. Slater Tetrahedron Letters 1968 3699. lS9 T. C. Jones Diss. Abs. 1967,28B 106. 160 K. Okamoto S. Fukui I. Nitta and H. Shingu Bull. Chem. SOC.Japan 1967,40 2350 2354. 130 N. S. Isaacs Muchin et ~2.'~'Very low activation entropies (down to -47 e.u.) and low Arrhenius activation energies (e.g. 7.3 kcal.mole-') were quoted. When heated in dichloromethane allylbenzylmethylphenylammonium iodide displacement undergoes at the benzylic carbon-mild conditions for such a reaction,162 the basic hydrolysis of tetranitromethane evidently occurs by displacement of the trinitromethyl anion from nitrogen by OH-and also by NO,.'63 The + N-Me /u Me decomposition of NN-dimethylpiperidinium ions of fixed conformation (e.g.tropine camphidine derivatives) by thiophenoxide involves preferred attack at the axial methyl group [see (128)l. 164 The bridgehead halogen in 1-adamantyl bromide is by no means inert towards hydrolysis in aqueous dimethyl sul- phoxide (k = 1.25 x 10-' 1.nole-'set.-' at 50" AH' = 20.4 k~al.mole-').'~~ A 2-phenyl group activates cyclopropyl chloride towards acetolysis by a factor of 104,166and vinylic halides containing a P-aryl substituent have also been shown to undergo substitution by strong nucleophiles such as thiophenoxide and methoxide.Such displacements on PP-diary1 halides show a Hammett p value of 5.1 indicating a high degree of carbanion character in the reaction. 16' The strong carbon-nucleophile thiophenoxide forms substitution products with both cis-and trans-p-nitro-P-bromostyrenes (possibly by addition-elimination) whereas the strong base methoxide brings about a considerable proportion of elimination to the acetylene.168* 169 R Et,Sn + Hg1,-EtHgI + Et,SnI R ' (129) .'Hi1 % HgI 16' G. Muchin R. Ginsberg and S. Moissieva Ukrain Chem. J. 1926 2 136; Chem. Zentr. 1926 2376. 16' K. T. Leffek and F. H. C. Tsao Canad. J. Chem. 1968,46 1215. 163 D. J. Glover J. Phys. Chem. 1968,72 1402.164 B. G. Hutley J. McKenna and J. M. Stuart J. Chem. SOC.(B),1967 1199. 16' J. Delhoste G. Gomez and G. Lamaty Compt. rend. 1968,266 C 1468. 166 J. W. Hausser and N. J. Penkowski J. Amer. Chem. SOC.,1967,89,6981. P. Beltrame D. Pitea and M. Simonetta J. Chem. SOC.(B),1967 1108. G. Marchese F. Naso and G. Modena J. Chem. SOC.(B) 1968,958. 169 G. Marchese G. Modena and F. Naso Tetrahedron 1968,24,663. Reaction Mechanisms 131 Several new electrophilic substitution reactions have been studied ;l70-’ 72 the activation parameters of the metal-exchange reaction (129) (AS* = -30e.u. AH* = 11.7 kcal.mole-’) indicate a tightly bound transition state such as (130) but the presence of a large positive kinetic salt effect suggests that (130b) is a better representation.1737 174 Possibly rigidity could be conferred on the latter by virtue of its crowded nature and the Coulombic forces present. Electro- philic displacements on allenyltin compounds have been shown to lead to allenic and acetylenic products by SE2 and SETmechanisms respectively,’ 75 the rates being somewhat greater than those of allylic analogues. Orbital overlap considerations have been suggested as responsible for the stereo- chemistry of bimolecular displacement reactions. Salem 176 has suggested that overlap of the lone-pair orbital in the nucleophile with the rearside lobe of the C-X antibondingo* orbital (being energetically and sterically most accessible) accounts for inversion while an attacking electrophile will need to approach the filled C-X a-orbital from the front leading to the often-observed retention of configuration.An attempt has been made to account for the stereochemistry of S,’ and S,’ reactions in molecular orbital terms. For nucleophilic displace- A ments new orbitals are constructed by mixing of the lowest vacant orbital of the allyl cation (the nonbonding orbital $J with 2s atomic orbitals on each carbon leading to the situation (131). Maximum overlap in the SN2 reaction required to be bonding to both N and X is achieved by an anti- geometry while for the SN1’transition state requiring bonding overlap to N :and antibonding overlap to X:the syn-geometry is most favourable. Similar arguments apply to SE reactions with the allyl anion now as basis.177 Such predictions should be amenable to experimental test.Carbaniom.-Hydrocarbon acidity has been reviewed.’ 78 The kinetic and thermodynamic acidities of some di- and tri-arylmethanes have been compared and shown to correlate in a nonlinear rnanner.l7’ In particular it appears that D. J. Cram and W. D. Kollmeyer J. Amer. Chem. SOC.,1968,90,1779 1784 1791 171 D. J. Cram W. T. Ford and L. Gosser J. Amer. Chem. SOC.,1968,90,2598. ’’’ W. T. Ford and D. J. Cram J. Amer. Chem. SOC., 1968,90,2606,2612. M. H. Abraham and T. R. Spalding J. Chem. SOC.(A),1968,2530. M. H. Abraham and T. R. Spalding Chem. Comm. 1968,46. 175 H. G. Kuivila and J. C. Cochrane J. Amer. Chem. SOC. 1967,89,7152. L. Salem J. Amer. Chem. SOC. 1968,90 543 553. 177 N. T. Anh Chem. Comm.1968 1089. H. Fischer and D.Rewicki Prog. Org. Chem. 1968,7,116. 179 D. J. Cram and W. D. Kollmeyer J. Amer. Chem. SOC. 1968,90,1784. 132 N. S. Isaacs isotopic exchange for the weaker carbon acids goes on at a higher rate than would be expected from their dissociation equilibria. The stereochemistry of carb- anions depends upon substituent groups. Highly conjugating substituents (and perhaps also crystal lattice requirements) can induce planar geometry as in the dinitrobutenamide ion (132) the crystal structure of which has been 0 0 H' reported. 8o The observation that deuterium exchange occurs at the carbon a to the carboxy-group rather than that a to the sulphonyl group in (133) (although the latter should be more acidic) has been explained by supposing that the latter carbanion if formed would be pyramidal and unable to invert on account of the methylene bridge hence bringing no relief of steric interac- tions between the two endo-groups.The carboxyl carbanion which forms in the basic medium is planar and hence can relieve steric strain.181 Also Streitweiser and Mares have shown that whereas two a-fluorine atoms greatly enhance the kinetic acidity of toluene (by a factor of lo4) a 9-fluorine atom diminishes the acidity of fluorene. This has been explained in terms of the conjugative destabilisation of the planar 9-fluorenyl anion in contrast to the inductive stabilisation of the pyramidal benzylic anion. 182 The allylic anion (134) shows restricted rotation about the C(lFC(2) bond as manifest by the collapse at go" of the multiplet absorption due to H2 coupled to H and H,.The enthalpy of activation is 19.8 kcal.mole-'. Rotation about.the C(3)-phenyl bond is also observable since at low temperatures the two phenyl Ar 'H H (134) (135) ortho-protons become distinct AH* for this process is 13-9 kcal.mole-1.'83 Vinyl carbanions are stabilised by adjacent sulphur. The compound (135) J. R. Holden and C. Dickinson J. Amer. Chem. SOC.,1968,90 1975. '13' G. Maccagnani F. Montanori and F. Taddei J. Chem. SOC.(B),1968,453. A. Streitwieser and F. Mares J. Amer. Chem. SOC.,1968,90 2444. V. R. Sandel S. V. McKinley and H. H. Freedman J. Amer. Chem. SOC.,1968,90,495. Reaction Mechanisms exchanges the 2-vinyl proton in NaOD-D,O without cis-trans isomerization and the sulphoxide and sulphone (136; X = SO SO,) also give carbanions of high conformational stability.'84 The emphasis upon C-H ionisation as a rate-determining step in the Favorskii rearrangement shifts towards greater carbanion character in the transition state as the leaving group varies from C1-to Br- to I- as judged by the increasingly large primary isotope effects (4-0,4-2 and 5.1 respectively)' 85 while 4,4-diaryl-2-chlorocyclohexanones react in the Favorskii rearrangement much more slowly than 2-chlorocyclo- hexanone but show a greater propensity towards "-deuterium exchange. Apparently reversible formation of a more stabilised carbanion occurs in the former case.'86 On the other hand 1 -bromobicyclo[3,3,1]nonan-9-one 0 0 c1 C02H >"=H +b-undergoes rearrangement with no deuterium exchange with solvent while 1-bromobicyclo[5,3,1]undecan-l1 -one incorporates one atom of deuterium per molecule during rearrangement.It is suggested that the former reacts by a semi-pinacolic mechanism rather than via the more usual cyclopropanone '" even though it possesses an a-hydrogen atom. If so the reason is presumably steric such as the strain imposed in forming a tricycl0[3,3,1,0~*~]nonane system. This observation can also be taken as evidence in favour of the normal cyclo- propane intermediate (137) rather than a dipolar ion (138) which would pre- sumably have less steric requirements than are shown. '88 The base-catalysed 1,3-proton-migration in 1,3-dimethylindene is stereospecific and leads to racemization with deuterium exchange.Amines however lead to exchange rates considerably in excess of racemization rates,' 89 suggesting a component of either rear-face attack of D+ at C-3 or front-face attack at C-1 (139). A number of new studies have been made of carbanion formation by base- catalysed proton exchange. Exchange and other accompanying reactions in olefins has been reviewed.lgO Strongly (-I +M) groups such as OMe de- activate a-hydrogens towards ionisation and exchange. Whereas a-hydrogen G. Maccagnani and F. Taddei Boll. sci. Fac. Chim. ind. Bologna 1968,26 71 83. la' H. R. Nace and B. A. Olsen J. Org. Chem. 1967,32,3438. la6 F. G. Bordwell R R Frame R G. Scamehorn J. G.Strong and S. Meyerson J. Amer. Chem. SOC.,1967,89,6704. la7 E. W. Warnhoff C. M. Wong and W. T. Tai J. Amer. Chem. SOC.,1968,90,514. la' G. Bergson and A. Weidler Acta Chem. Scand. 1963,17 1798. la9 J. Almy R. T. Uyeda and D. J. Cram J. Arner. Chem. SOC.,1967,89,6768. 190 C. D. Broaddus Accounts Chem. Res. 1968 1,231. 134 N. S. Isaacs exchange rates in compounds XYCH*CO,Rfor a wide variety of substituent groups X Y correlate quite well by the Taft (o*, p*) equation with a p*-value of 1.78,the compounds with an a-methoxy or fluorine substituent (X Y = MeO H ; F,H ; Me0,MeO ; F,F)are less active than predicted by the linear free-energy relationship by factors 104.7,lo7,and lo1 respe~tively.'~' These large disagreements must indicate that the factors measured by the Taft equation are not the most important in these cases.Possibly repulsive interactions between adjacent unshared pairs of electrons on carbon and on oxygen or fluorine account for these discrepancies. The effect is evidently a short-range one since fluorine in an aromatic ring labilises the benzilic hydrogen. 192* Exchange studies on sulphones have shown that the acidity of the a-hydrogen is diminished by an a-alkyl or alkenyl group and this to a greater degree than in ketones and nitro-alkanes. Ally1 sulphones exchange hydrogen only at the a-position (CH,). The acidity of the proton in a series of alkyldinitromethanes varies over two pK units according to the nature of the alkyl group. It appears that the bulk of the group is the factor most influencing acidity perhaps by affecting the planarity of theC(NO,) group by which the carbanion achieves stability.Hydrogen exchange in (140)occurs more rapidly by a factor of lo4 than in the cyclopropenyl analogue (141).'96Presumably the anion derived from the latter Ph Ph Ph Ph compound is destabilised by the antiaromatic 4n system. It has been pointed out that H-scales have a considerable dependence on the nature of the metal- ion associated with the base used on account of ion-pair association and that therefore correlations of rates with these acidity scales should be made and 19' J. Hine L. G. Mahone and C. L. Liotta .I. Amer. Chem. SOC.,1967,89 5911 19' R. Filler and C. S. Wang Chem. Comm. 1968 287. 193 A. Streitwieser and F.Mares J. Amer. Chem. SOC. 1968,90 644,648. lg4 C. D. Broaddus J. Arner. Chem. SOC. 1968,90,5504. lg5 M. E. Sitzmann H. G. Adolph and M. J. Kamiet J. Amer. Chem. SOC.,1968,90 2815. 196 R. Breslow and M. Douek J. Amer. Chem. SOC. 1968,90,2698. Reaction Mechanisms 135 interpreted with caution. lg7 The rate of proton exchange of acetophenone in the presence of OD-decreases with the cation present according to the order Mg2+ > Ca2+ > Ba2+ > Li' > Na' > K+,lg8 the order expected for decreasing coulombic association. Exchange in isopropyl methyl ketone occurs preferentially at the methyl hydrogen the methyl :methine rate ratio being 21 :1; in the structurally analogous methyl cyclopropyl ketone this rztio is 2225:l mainly due to diminished reactivity at the cyclopropane ring.lg9-'01 Diamines appear to enhance the reactivity of dimethylmagnesium towards the carbonyl group; a possible interpretation allows the amine to co-ordinate to the metal thus loosening the Mg4 bond (142).202 The enolate anion of benzocyclobutanone is very reactive towards C-C bond-cleavage and leads to dimeric pr~ducts.~"~ Ring-cleavage of the cyclo-octatetraenyl dianion is accomplished by acetyl chloride leading to the all-cis-dodecatetraene- 2,l l,-dione.'04 Nonclassical structures have been proposed for some carbanions. The monohomocyclo-octatetraene anion-radical has been prepared and its electron resonance spectrum has been recorded ;'05 the enhanced acidity (by a factor of lo4) of (143) compared to the mono-01efm,206 is considered due to n-participation in the 6n-structure [see (144)l.The n.m.r. spectrum of the 1,4-dianion of 1,1,4,4-tetraphenylbut~ne,~~~ shows the resonances of the three types of aromatic protons well separated on account of their differing inter- actions with the negative carbon atom (ortho z 2-9 meta 53 and para 4-3). The tetraphenylethylene anion-radical disproportionates reversibly to olefin and dicarbanion in ether although in hexamethylphosphoramide solution the equilibrium favours the anion-radical. '08 Coupling between radicals and carbanions has been demonstrated [e.g. (145)] a reaction which could prove useful ~ynthetically.~~~~ 'lo A base-catalysed rearrangement pathway from y2 Me / -Ph OzN-c-+ Q -e \ Me Me (146) 197 J.R. Jones Chem. Comm. 1968,513. 19' J. R. Jones Trans. Faraday SOC. 1968,64,440. 199 C. Rappe and W. H. Sachs Tetrahedron 1968,24,6287. 2oo C. Rappe and W. H. Sachs J. Org. Chem. 1967,32,4127. 201 J. Warkentin and C. Barnett J. Amer. Chem. SOC.,1968,90,4629. 202 H. 0.House and J. E. Oliver J. Org. Chem. 1968,33,929. 203 D. J. Bertelli and P. Crews J. Amer. Chem. SOC.,1968,90,3389. 204 T. S. Contrell and H. Shechter J. Amer. Chem. SOC.,1967,89 5868 5877. 205 F. J. Smentowski R. M. Owens and B. D. Faubian,J. Aver. Chem. SOC. 1968,90,1537. '06 J. M. Brown and L. V. Occolowitz J. Chem. SOC.(B),1968,411. 207 K. Takahashi and R. Asami Bull. Chem. SOC.Japan 1968,41,231. A. Cserhegyi J. Chandhuri E. Franta J. Jagur-Gradzinski and M.Szwarc J. Amer. Chem. SOC. 1967 89 7129. 209 G. A. Russell and W. C. Danen J. Amer. Chem. SOC.,1968,90,347. 'lo W. C. Danen Diss. Abs. 1968,28 B. 3639. 136 N. S. Isaacs epoxide to carbonyl compound (cfithe acid-catalysed reaction) has been shown to operate via the carbanion of (146).211 Reactions at the Carbonyl and Related Groups.-The complex interplay of steric and inductive effects among reagents and solvents continues to invite investigation. Esterification and ester hydrolysis are among the most common reactions studied for this purpose. The esterification by diphenyldiazomethane of meta-substituted benzoic acids in 14 mainly polar solvents has been studied and rate data have been recorded. Linear free-energy relationships were ob- served and the dependence of the rates on solvent followed moderately well a dielectric constant function.212 There is a problem in correlating rates with solvent properties however since proportions of monomeric and dimeric carboxylic acids change from solvent to solvent each form presumably having a different reactivity; more information would be welcome on the solvent de- pendence of these equilibria.A mechanism supported by kinetic evidence has been suggested for the esterification of benzoic acid by diphenyldiazomethane in toluene in which the reagents form an initial 1 :1 complex which is decom- posed by three routes uncatalysed and catalysed by monomeric and dimeric acid forms. The effects of trans-4-substituents on the esterification of cyclohexane- carboxylic acids shows a considerable increase in rate with increasing -I character of the substituent-a 10-fold rate increase from the 4-H to 4-OH compounds.l4 Steric factors are evidently of prime importance in the hydrolysis of trans-decalincarboxylic esters to judge from the greater reactivity of the 2-compared with the 1-esters and of equatorial over axial isomers.215 However it is unwise to make such generalizations since other factors may intervene. For instance the relative reactivities of cyclohexanecarboxylic esters and their 4-t-butyl analogues change with solvent the former being hydrolysed more readily in aqueous media and the latter in alcoholic. Although these effects may be explained in terms of changes in the axial :equatorial ratio especially of the unsubstituted esters their correct interpretation may be more subtle.From the acid-catalysed esterification of ortho-substituted benzoic acids two effects upon the variation of ASs with substituent have been suggested;216 an increase due to steric inhibition of solvation in the transition state is offset by a decrease due to the bulk of the substituent itself directed against the reac- tion site. All ortho-substituents depress AHS relative to hydrogen. Isotopic tracers have been used to show that the acid-catalysed ester exchange reaction,2 l7 involves alkyl-oxygen fission at the ester and the acetate-catalysed methanolysis of aryl acetates proceeds by a symmetrical intermediate presumably acetic an- "' G. R Treves H.Stanger and R. A. Olafson J. Amer. Chem. SOC., 1967,89,6257. '"A. Buckley N. B. Chapman M. R J. Dack J. Shorter and H. M. Wall J. Chem. SOC.(B),1968 631. 213 N. B. Chapman A. Ehsan J. Shorter and K. J. Toyne Tetrahedron Letters 1968 1049. '14 N. B. Chapman A. Ehsan J. Shorter and K. J. Toyne J. Chem SOC.(B),1968 931. '15 N. B. Chapman A. Ehsan J. Shorter and K. J. Toyne J. Chem. SOC.(B),1968 178. 2'6 N. B. Chapman M. G. Rodgers and J. Shorter J. Chem SOC.(B) 1968,157. 217 V. D. Parker and A. W. Baker. Chprn. Cornrn. 1968,691. Reaction Mechanisms hydride.2’8 This postulate was confirmed by Gold et al. by trapping this inter- mediate as acetanilide by addition of aniline to the reaction.219 The effects of different acids on several types of acid-catalysed ester hydrolysis have been studied by Bunton and his co-workers.220 For methyl 2,4,6-trimethylbenzoate (reacting by the AA,l mechanism) and t-butyl esters (AA1l) the catalytic order is HClO > H2S04 > HCl whereas in A,2 reactions the order is reversed.It was concluded that the anions play a part in the stabilisation of the transition state and that anions of a low charge-density stabilise best a transi-tion state with carbonium character while the opposite applies to transition states (such as the AA,2) in which there is considerable hydrogen-bonding to solvent. It was found that the salt effects upon the stability of the tri-p-methoxy- benzyl carbonium ion were in the order NaClO > LiClO > NaS0,Me > NaBr > NaCl > LiCl.The Reformatsky reaction between (+)-methyl-a- bromobutyrate and benzaldehyde has been reported to give optically active methyl a-ethyl-P-hydroxyhydrocinnamate.* Elimination.-An examination of the distribution of elimination products from the reaction of methoxide on 2-halogenohexanes (hex-1-ene cis and tram-hex-2-enes) has been made with a view to examining the validity of the theory222 that steric factors are primarily responsible for the direction of elimination. It was found that under E2 conditions the amount of hex-1-ene steadily decreased and the hex-2-enes increased as the leaving group was increased in size from fluoride to chloride bromide and iodide the reverse of what might be expected from a consideration of steric factors.223 Moreover the rates of formation of terminal olefin were accurately related to the rates of formation of cis-and tram-2-olefi11 separately suggesting that all three arise from the same transition state.These observations were interpreted by donsider- ation of a continuum of mechanistic types within the scope of the E2 mechanism varying from the ‘nearly El’ (147) through an intermediate type (148) to a ‘nearly carbanion’ type (149) with some degree of carbanion character on the P-carbon. The orientation of elimination is governed by the nature of the R. L. Schowen and C. G. Behn J. Amer. Chem. SOC.,1968,90,5839. V. Gold D. G. Oakenfull and T. Riley J. Chem. SOC.(B) 1968,515. 220 C. A. Bunton J. H. Crabtree. and L Robinson. J. Amer. Chem. SOC.,1968 m1258.221 J. Canceill. J. Gabard. and J. Jacsues. Bull. SOC.chim. France. 1968. 231. 222 H. C. Brown and I. Moritani J. Amer. Chem. SOC.,1956,78,2203. 223 R. A. Bartsch and J. H. Bunnett J. Amer. Chem. SOC. 1968,90,408. 138 N. S. Isaacs transition state ;thus since an a-alkyl group stabilises the intermediate and ‘nearly El’ transition states more than the ‘nearly carbanion’ one where the latter prevails Hoffman elimination will be preferred. The leaving group has an effect on the nature of the transition state which in the sequence from iodo to fluoro show a trend towards the ‘nearly carbanion’ as the electronegativity of the leaving group increases. The elimination of hydrogen halide from 3-halogenopropanes shows different values of the hydrogen isotope effect for the formation of cis-and tr~ns-pent-2-enes.’~~ However depending on the solvent used either may be the larger which suggests that this (rather small) isotope effect is bound up with solvation of the transition state rather than fundamental differences in mechanism for the two modes of elimination.Further evidence which envisages a continuum of mechanisms for elimination has been presented B6+ H I J__--It I * X6- 6‘B H’ I 7/.--‘v I I X6- I I H B;--1cI X6 - Y Ye Me-C -CH/\ CN Me E2H Intermediate E2C (150) (151) by Parker et ~1.~~~9 226 who suggest a shift in emphasis of attack by the base from the P-hydrogen (E,H-mechanism) through a transitional type to attack on the a-carbon (E,C) though the latter is distinct from an S,2 transition state (150).The evidence comes from correlations observed between elimination rates and either carbon nucleophilicities or bacicities (hydrogen nucleophilicities) of the base in a Brqhsted plot. Thus cyclohexyl toluene-p-sulphonate in aqueous medium correlates best with the carbon nucleophilicity and is deduced to follow an E2C path. It is concluded that the mechanism is affected by the nature of the leaving group ; weakly nucleophilic leaving groups prefer E,C mechanisms while stronger ones tend to react by E,H routes. Two eliminations with the characteristics of a prior reversible dissociation (E,cb mechanism) have been described first the trans-elimination of erythro-4,4’-dichlorochalconedi-chloride in ethanol is inhibited by acids2” while conditions suggested228 as being most likely to result in E,cb elimination-a strongly acidic P-hydrogen strong base and a poor leaving group-are met in compound (151) which shows the expected kinetic form in elimination of HCN.Carbanion mechanisms of elimination have been reviewed. 229 El -Mechanisms for acid-catalysed 224 D. L. Grifith and B. Singerman Chem. Comm.,1968,438. 225 A. J. Parker M. Ruane G. Biale and S.Winstein Tetrahedron Letters 1968 2113. 226 D. J. Lloyd and A. J. Parker Tetrahedron Letters 1968,5183. 227 T.I. Crowell R. T. Kemp R. E. Lutz and A. A. Wall J. Amer. Chem. Soc. 90,4638. 228 Z. Rappoport Tetrahedron Letters 1968,3601. 229 D. J. McLennan Quart. Rev. 1967,21,490. Reaction Mechanisms I39 dehydrations of benzyl alcohols are indicated by two lines of research.A positive p-value of considerable magnitude is characteristic of dehydrations of 1-methyl-2-aryl-2-hydroxypropionicacids’ 30 while eliminations from 1,2-diphenylethanols substituted in both rings are best correlated by a com- pound Hammett expression involving a function of 0’ for the adjacent group showing conjugation and 0 for the nonadjacent group showing only an in- ductive interaction. 31 It has been pointed out that isomerization of terminal to nonterminal olefins may occur in the presence of strong bases,232 a process which is not always examined in studies of the orientation of base-catalysed elimination. Although E reactions have hitherto been assumed to proceed by an anti-geometry several authors have provided evidence that considerable proportions of syn-elimination can occur especially in medium-ring compounds.Sicher’s group in Prague have studied eliminations in medium- and large-ring cycloalkanes from which both cis- and trans-olefins are formed. They conclude that the cis-isomers arise from anti-elimination but the trans-olefins mainly by a syn-pro~ess.’~~ These conclusions rest on two lines of evidence firstly on the isotope effects and olefin isotope content of stereospecifically labelled p-deuterio-compounds and secondly on the more equivocal conclusions drawn from rate-profile measurements-the charactwistic and different dependence of cis-and trans-olefin formation rates as a function of ring size. These rates are equated with anti- and syn-elimination rates by the isotopic labelling technique in certain cases.The results show that the rate of trans-olefm formation from cycloalkylammonium hydroxides reaches a maximum at the Clo ring while cis-olefin formation maximises at C12.The effects of different leaving groups bases and solvents were studied. Very high stereospecificity was reported for elimination of ammonium ions (Hofmann elimination) under a wide variety of conditions and similarly for some toluene-p-sulphonate. The bromides elimi- nated in a stereospecific manner in t-butoxide-t-butyl alcohol but in more polar media (ethoxide-ethanol or t-butoxide-dimethylformamide) anti-elimination geometries were reported to give both cis-and trans- olefins. The evident nonequivalence of the P-protons may be rationalised in terms of the supposed preferred conformations of the macrocyclic rings although little unequivocal evidence on this is available.The deuterium-labelling technique was also used to demonstrate that cyclo-ostyltrimethylammonium bromide gives 35 % cis-cyclo-octene by a mixture of 85 % anti- and 15% syn-elimination routes while the 65 % trans-cyclo-octene formed originated by an entirely syn-mechanism. 34 Varying proportions of syn-elimination were reported 230 D. S. Noyce and S. K. Brauman J. Org. Chem. 1968,33,843. 231 D. S. Noyce D. R. Hartter and F. B. Miles J. Amer. Chem. SOC. 1968,90 3794. 232 B. Blouri C. Cerceay and P. Rumpf Ann. Chim. (France) 1968,3 127. 233 J. Sicher and J. Zavada Coll. Czech. Chem Comm.1967 32 2115 2122; J. Zavada and J. Sicher ibid. 3701; M. Pankova J. Zavada and J. Sicher Chem. Comm. 1968 1142; J. Zavada M. Pankova and J. Sicher ibid. 1145; J. Sicher J. Zaved and M. Pankova ibid. 1147 J. Sicher and J. Zavada Coll. Czech. Chem. Comm. 1968 33 1278; J. Zavada J. Krupicka and J. Sicher ibid. p. 1393. M. Svoboda J. Zavada and J. Sicher ibid. 1415; M. Havel J. KrupiEka M. Svoboda J. Zavada and J. Sicher ibid. p. 1429; J. Sicher M. Tichy J. Zaved and J. KrupiEka ibid. p. 1438. 234 J. L. Coke M. P. Cooke and M. C. Mourning Tetrahedron Letters 1968 2247. 140 N. S. Isaacs from cyclobutyl(90 %) cyclopentyl(46 %) cyclohexyl(4 %) cycloheptyl(35 %) 3,3-dimethylcyclopentyl (76 %) and norbornyl (100 %) trimethylammonium-hydroxides using specifically labelled compound^.^ 5-2 37 It seems likely that both processes require coplanar arrangements of the leaving group P-proton and two carbon atoms.The compounds which give the most syn- transition state but not a planar anti-transition state. Where both planar syn- and anti-conformations are equally possible the latter seems favoured as oox X = CS*SMe (1 52) (153) cis (154) trans shown in the elimination of the toluene-p-sulphonate (152) from which hardly any syn-product was discernable. '38 More information of the thermodynamics of these two processes would be welcome and also whether the results are affected by the incursion of an El component with subsequent hydride (deuteride) migration. The elimination of the xanthates (153) and (154) gives A'-and A'- olefins with k,/k = 1.5.A syn-mechanism (six-centre transition state) is indicated but the A'-olefin derived from the cis-xanthate still contains up to 44% of the deuterium.239 It would appear that when an anti-elimination is forced carbonium ion-pair mechanism is favoured. Rapid hydride (deuteride) shift then occurs giving a tertiary carbonium ion which then eliminates a proton or deuteron statistically. The methide shift which occurs during the elimination from ( +)-[2H)neopentyl toluene-p-sulphonate does so stereo-specifically the ['HI isopentene produced having retained c~nfiguration.~~' The elimination of halogen halide from cla-dimethylphenethyl halides which occurs by an E mechanism with considerable carbonium character (p = -1.5) gives quite large amounts (20%) of nonconjugated ~lefin.~~~ Di- and tri- chloroethanes have been found to eliminate hydrogen chloride at very high rates on molecular seive the products being mixtures of cis- and trans-1,Z and 1,l-dichloroethylenes from the latter.242 The very high primary isotope effects observed during the elimination by alkyl lithium of cis- and trans-1-chloro- [2H]~tyrene'~~ (kdkD = 8 and 15 respectively,) is explained by an E,cb 235 M. P. Cooke and J. L. Coke J. Amer. Chem. SOC. 1968,90,5556; J. L.Coke and M. C. Mourn- ing ibid. 5561. 236 J. L. Coke and M. P. Cooke Tetrahedron Letters 1968 2253. 237 J. L.Coke and M. P. Cooke J. Amer. Chem SOC. 1967,89,6701. 238 D. H.Froemsdorf W. Dowd W. A. Gifford and S.Meyerson Chem. Cornm. 1968,449. 239 W.S.Briggs and C. Djerassi J. Org. Chem. 1968,33 1625. 240 G. Sollaide M. Muskatirovic and H. S. Mosher Chem Comm. 1968 809. 241 L. F.Blackwell A. Fischer and J. Vaughan J. Chem. SOC.(B),1967 1084. 242 I. Mochida and Y. Youeda J. Org. Chem. 1968,33,2161. 243 M. Schlosser and V. Ladenberger,Chem. Ber. 1967,100,3877,3893,3901. Reaction Mechanisms 141 mechanism-the first instance of such a process (155). The Cope elimination of the asymmetric amine oxide (Ma) leads to optically active 4-methylcyclo- hexene. 44 Polar Additions.-The carbonium ion-like transition state for polar additions receives support from several lines of work. The hydroxymercuration of olefins shows a Taft p*-value of -3.3 from the linear correlation of log k with o*.~~’ The acid-catalysed hydration of phenylbenzoylacetylenes in strongly acid solution shows a dependence of log k on H with p = -4.2 and a correlation witho+.246 The hydrolysis of phenyl vinyl ethers has p = -2.21 but now log k correlates with o rather than 0’ since the substituent and positive centre are separated by oxygen.247 Stereochemical investigations include the report that bromine addition to 1 -phenylpropene and to trans-anethole occurs non-stereospecifically presumably by way of a carbonium rather than a bromonium ion.24 The substituted bicyclo[2,1,0]pentane (156) undergoes cis-catalytic hydrogenation mainly on the exo-side ;249 bicyclo[2,1,1] hex-2-ene adds mer- curic acetate DCI and deuterioacetic acid in cis-fashion but benzenesulphinyl chloride in a trans.250 @-Unsaturated acids have been shown to be less reactive towards bromide addition than their conjugate bases which presumably are able to stabilise positive charge on the a-carbon atom.251 By simple fickel MO theory it has been calculated (in agreement with experiment) that 1,2- hydrohalogenation of butadiene and isoprene is kinetically favoured as is 1,4:addition to chloroprene ; 1,4-addition is thermodynamically favoured by each diene.252 Fluorine diluted with fluorocarbon at -78”will add smoothly to acetylenes to yield 1,2,2,2,-tetrafluorohydrocarbons ;253 iodine nitrate generated from silver nitrate and iodine adds to cholestene with the formation of 2-ct-nitrato-3,P-iodocholestane.254 The metallation products of cyclic olefins depends on both ring size and base;255 either the vinyl or allylic metal derivative may be formed according to the conditions.A bromonium ion intermediate is implicated in the addition of bromine to unsaturated esters as judged by the trans-stereochemistry ;2 56 a charge-transfer complex inter- mediate has also been proposed for this rea~tion.~” An interesting observation of steric inhibition of resonance has come from bromination on studies on (157) and (1 58) for the former the rate of bromine addition is a function of the 244 F. L. Lam Diss.Abs. 1967,27B 4266. 245 J. Halpern and H. B. Tinker J. Amer. Chem. SOC.,1967,89,6427. 246 D.S.Noyce and K. E. deBruin J. Amer. Chem. SOC.,1968,90,372. 247 T.Fueno I.Matsumura T. Okuyama and J. Furukawa Bull. Chem SOC.Japan 1968,41,818. 248 R.C.Fahey and H-J. Schneider J. Amer. Chem. SOC.,1968,90,4429. 249 M.~J. Jorgenson Tetrahedron Letters 1968,4577. 250 F.T.Bond J. Amer. Chem. SOC.,1968,90,5326. 251 R.P.Bell and D. Dolman J. Chem. SOC.(B),1968,500. 252 M.D. Jordan and F. L. Pilar Theor. Chim. Acta 1968 10,325. 253 F.Merritt J. Org. Chem. 1967,32,4124. 254 J. E.Kropp A. Hassner and G. J. Kent Chem. Comm. 1968,906. 255 C. D.Broaddus and D. L. Muck J. Amer. Chem. SOC., 1967,89,6533. 256 G.Hueblin and R. Steudel Z. Chem. 1968,8 108. ’” F.Gamier and J-E. Dubois Bull. SOC.chim. France 1968,3797. 142 N. S. Isaacs Ph LI L H Ph- E- Li Ph Ph Me’ Ni‘CH,C(Me) 0- (156) x (158) Hammett constant 0,while for the latter of the polar constant o+.258 Thus considerable carbonium-character of the transition state must reside on the benzilic carbon which can only become co-planar with the phenyl group in (158).The chlorination of ap-unsaturated carbonyl compounds in acetic acid has been interpreted as partaking of a variety of mechanisms:chloronium-ion attack especially on rather electron-poor double-bonds ion-pair formation from molecular chlorine addition to more nucleophilic double-bonds and some cis-addition. 59 258 A. F. Hegarty and J-E. Dubois Tetrahedron Letters 1968,4839. 259 M. D. Johnson and E. N. Trachtenberg J. Chem. SOC.(B),1968. 1018; M. C. Cabaleiro M. D. Johnson B. E. Swedlund. and J. G. Williams. ihid.. 1022; M C.Cabaleiro. C. J. Cooksey M. D. Johnson B. E. Swedlund and J. G. Williams ibid.,p. 1026.

ISSN:0069-3030    

DOI:10.1039/OC9686500103

出版商:RSC    

年代:1968

数据来源: RSC

摘要:

3 (Part iii) REACTION MECHANISMS By A. Ledwith (Donnan Laboratories University of Liverpool) Orbital Symmetry Correlations.-‘Orbital symmetry controls in an easily discernible manner the feasibility and ,stereochemical consequences of every concerted reaction’. Conservation of orbital symmetry as exemplified in the Woodward-Hoffman rules’ for organic reactions occurring in a concerted manner has now become an established landmark in the interpretation of reaction mechanisms. Appli- cation of Woodward-Hoffman rules to the most common types of cycloaddi- tion cycloelimination electrocyclic reactions and sigmatropic rearrangements has been further reviewed by Woodward and Hoffman,’ by Volmer and Ser~is,~ and more exhaustively by Gill4 and by Miller.5 The last review is particularly stimulating on two counts.It attempts to place orbital symmetry correlation in perspective with respect to the general development of theories relating to organic reaction mechanisms and it demonstrates clearly defined correspond- ence between the Woodward-Hoffman approach’v ’ and the more theoretical treatments of Longuet-Higgins and Abrahamson6 and Fukui.’ In addition to these general review articles application of orbital symmetry correlation to the simplest example of an electrocyclic reaction-the cyclopropyl -+ ally1 cation rearrangement-has been surveyed by DePuy. An important new application of orbital symmetry correlation has been deduced by McCapra’ for some reactions displaying chemiluminescence. Previous work has demonstrated that chemiluminescence in biochemical systems results from decomposition of four-membered cyclic peroxides.McCapra’ suggests that if decomposition of the peroxide is concerted then conservation of’ orbital symmetry in this electrocyclic reaction ensures the formation of an excited (luminescent) state of one of the carbonyl fragments. -. . ,C-0 ==C-=O -C = 0 bonding -7 ’ j-+ + >LA >c-:o ;C = O* antibonding R. Hoffmann and R. B. Woodward Accounts Chem. Res. 1968,1 17. ’ R. B. Woodward and R. Hoffmann J. Amer. Chem. Soc. 1965,87,395,2046,2511 4388,4389. J. J. Volmer and K. L. Servis J. Chem. Educ. 1968,45,214. G. B. Gill Quart. Rev. 1968,22 338. ’ S. I. Miller Adu. Phys. Org. Chem. 1968 6 185. H. C. Longuet-Higgins and E.W. Abrahamson .I.Amer. Chem. Soc. 1965,87,2045. ’ K. Fukui Tetrahedron Letters 1965. 2009 2427; Bull. Chem. Soc. Japan 1966 39 498; K. Fukui and H. Fujimoto Tetrahedron Letters 1966 251 (see also L. Salem J. Amer. Chem. SOC. 1968,90 543 553). * C. H. DePuy Accounts Chem. Res. 1968,1 33. F. McCapra Chem. Comm. 1968 155. 144 A. Ledwith In essence the Woodward-Hoffman rules predict 'allowed' pathways for concerted reactions having activation energies substantially lower than corres- ponding 'forbidden' pathways. It is not surprising therefore that estimates of the difference in activation energy between these pathways should have attemp- ted where sufficient data exist The first estimate by Braumann and Golden" predicted that the allowed conrotatory mode for isomerisation of bicyclo-[2,1,0]pent-2-ene (1) to cyclopentadiene (2) was favoured by a difference in activation energy of approximately 15 kcal.mole- '.This value was based on estimates of ground and transition state strain energies and some of the assump- (1) (2) tions were later challenged," leading to a revised estimate of approximately 10 kcal.mole-l. A second estimate of the relative rates of conrotatory versus disrotatory ring opening was made by Doorakian and FreedmanI2 from kinetic measurements on the reaction of 1,4-dimethyl-1,2,3,4-tetraphenyl butadienes. Thus for the allowed conrotatory isomerisation (3) +(4)the predicted pathway was shown to be favoured by an absolute minimum of 7 kcal.mole-'. Ph Ph Ph Ph 25"- Phn M e Me Ph (3) (4) cis-cis'trans-In addition to providing a theoretical basis for many well known concerted reactions the Woodward-Hoffman rules make predictions concerning stereo- chemistry ofproducts resulting from sigmatropic rearrangements.The latter are defined as transformations in which a o-bonded atom or group migrates from one end of a conjugated chain to the other. When the highest occupied molecular orbital of the conjugated system across which migration occurs is antisym- metric conservation of orbital symmetry in a concerted reaction requires that the migrating groups must also undergo an antisymmetric transformation. The group either transverses the nodal plane of the skeleton (antarafacial motion) or suffers an inversion of configuration above the nodal plane (supra- facial motion); e.g.for a rl,51 shift of hydrogen lo J. I. Braumann and D. M. Golden J. Amer. Chem. Soc. 1968,90 1920. E. C. Lupton jun. Tetrahedron Letters 1968,4209. l2 G. A. Doorakian and H. H. Freedman J. Amer. Chem. SOC..1968.90.5310 6896. Reaction Mechanisms D suprafacial antarafacial These predictions have stimulated experimental work; that of Berson and his collaborators on [1,3] and [1,5] sigmatropic rearrangements was referred to briefly in last year’s Report13 and has now been reviewed in detail by Berson.14 Particularly impressive is a completed and extensive experimental study of the thermal rearrangement of endo-bicyclo[3,2,0]hept-2-en-6-y1 acetate (5) to exo-norbornenyl acetate (6).Because of the fixed geometry the [1,3] signatropic transformation demonstrated to occur is necessarily suprafacial and in accord with prediction occurs with complete inversion of the configuration of the migrating group. Additional confirmation of the predictive powers of orbital symmetry correlations comes from the work of Brennan and Hill,” who have demonstrated inversion of configuration at migrating carbon in the [1,4] sigmatropic re- arrangement of bicyclo[3,l,0]hexan-3-ones (7) to bicyclo[3,1,O]hex-3-en-2-ones (8). Cycloaddition Reactions.-In recent years this topic has become increasingly important from both a theoretical and a synthetic viewpoint The growing volume of publications on cycloadditions indicates that ths general type of reaction merits a place beside the better known substitutions eliminations and additions.Prompted by this line of reasoning Huisgen16 l7 has recently published a cogently reasoned consideration of definition classification l3 H. M. R. Hoffman Ann. Reports 1967 4 159. l4 J. A. Berson Accounts Chem. Rex 1968 1 152. l5 T. M. Brennan and R. K. Hill J. Amer. Chem. Soc. 1968,90 5614. l6 R. Huisgen Angew. Chem. Internat. Edn. 1968 7 321. R. Huisgen R. Crashey and J. Sauer in S. Patai ‘The Chemistry of Alkenes,’ Interscience New York 1964 p. 739. 146 A. Ledwith Br cleavaw (7) /of bond a (8) (inversion) (retention) and characterisation of cycloadditions. Accordingly cycldadditions should be defined as inter- or intra-molecular reactions in which the total number of o-bonds increases without elimination of small molecules or ions and in which there is no cleavage of existing o-bonds.Intermolecular processes leading to the formation of four- five and six- membered rings are very common1’ (see later) but the corresponding intra- molecular reactions are not so well characterised. Recent examples include the transformations (9) -+ (10)l8 and those involving (11)” and (12).20 C,H40Me -P C,H40Me -P H H (12) A. Ledwith and D. Parry J. Chem. SOC. R 1967 41; D. W. Adamson and J. W. Kenner J. Chem. SOC. 1935,286; C. D. Hurd and S. C. Lui J. Amer. Chem. SOC.,1935,57,2656. l9 R. Huisgen W. Scheer and H. Huber J. Amer. Chem SOC. 1967 89 1753. *’ A.C. Cope A. C. Haven F. L. Ramp and E. R. Trumbull J. Amer. Chem. SOC. 1952,74,4867. Reaction Mechanisms In further extension of his argument HuisgenI6 has suggested that the pre- vious habit of classfying intermolecular cycloadditions as 1,2-or 1,4- etc. be discontinued. Instead the reaction should be classified according to the numbers of atoms or groups participating in the formation of the new ring. Thus the formation of cyclopropanes (13) from carbenes and olefins is classified as a 2 + 1 (+3) cycloaddition. RCHSH + CBr -+ RCH-CH, \/ CBr (13) Cyclobutanes (14) arise from 2 + 2 (+4) reactions and pyrazolines (15) from 3 + 2 (+5) systems. 2 CF,--CFz + CFZ-CF LF,-LF CH,=CH.CO,Me CH,=N=N++ - (14) C0,Me-0 (15) The new definition and classifications are completely independent of mecha- nism i.e.as to whether the reactions are concerted or multistep processes or whether singlet or triplet excited states are involved in photochemical reactions. For example the most common cycloaddition is the Diels-Alder reaction involving formation of six-membered rings [e.g.(16)]. Diels-Alder additions (‘1,4-cycloadditions’) are undoubtedly concerted in mechanism2’ and would be defined as 4 + 2 (+6) reactions. Six-membered rings (17) may also arise however from the recently discoveredZZ ‘1,4-dipolar additions’ which involve two steps but are also classified as 4 + 2 (-6) reactions. This latter class of cycloadditions has already proved of synthetic value23 J. Sauer Angew. Chem.Internat. Edn. 1967 6 16. ” R. Huisgen K. Herbig and M. Morikawa Chem. kr. 1967 100 1107; R. Huisgen 2. Chem. 1968,8 290. 23 H. Ulrich B. Tucker and A. A. R. Sayigh J. Amer. Chem. SOC. 1968 90 528. 148 A. Ledwith I PhN=C=O -NPh PhNYN'ph (17) 0 in the reactions between sulphonyl isocyanates (18) and carbodi-imides (19). It seems likely that the classification proposed by Huisgen will meet with widespread approval. 2 + 2 +4 Reactions. According to Woodward-Hoffmann rules concerted thermal 2 + 2 cycloadditions are forbidden whereas the corresponding photochemical reactions are allowed.' There are however two main types of 2 + 2 cycloaddition which occur thermally under comparatively mild con- ditions. Cyclobutane formation from halogenated alkene~~~? 25 constitutes one such class of 'forbidden' reaction and addition reactions of ketens the other.26-28 Considerable effort has been expended in mechanistic studies of these types of cycloaddition and a clearer picture of some of the intermediates is beginning to emerge.Bartlett and his collaborators have studied extensively the (gas phase) cycloaddition reactions of halogenated alkene~.~~~ 25 Thus the addition of 1,l- dichloro-2,2-difluoroethylene (20) to butadiene yields the cyclobutane (21) and not (22) suggestjng the intermediate diradical(23). Diradical(23) is about 8 kcal.mole-' lower in energy than (24) and at least 21 kcal.mole-' lower than (25). These energy differences between possible diradical structures if present in the transition states for their formation are great enough to guarantee that as little as 0.001 % of the product will have the reverse orientation if the diradical is an intermediate.Accordingly Bartlett has concluded24 that exclusive head-to- head orientation should result for almost all substituted olefins reacting via diradical intermediates.. Stepwise reactions are not subject to the rules relating to orbital symmetry' and so in this case the apparent anomaly is removed. 24 P. D. Bartlett Science 1968 159 833. 25 P. D. Bartlett G. E. H. Wallbillich A. S. Wingrove J. S. Swenton L. K. Montgomery and B. D. Kramer J. Amer. Chem. Soc. 1968,90,2049;J. S. Swenton and P. D. Bartlett J. Amer. Chem. Soc. 1968,90,2056. 26 R. Huisgen L. A. Feiler and P.Otto. Tetrahedron Letters 1968 4485. 27 R. Huisgen and P. Otto Tetrahedron Letters 1968 4491. 28 G. Binsch L. A. Feiler and R. Huisgen Tetrahedron Letters 1968 4497. Reaction Mechanisms CF2 It CCI P Further evidence for the stepwise diradical nature of cycloadditions in- volving (20) was obtained by a study of its reactions with cis-and trans-double bonds of the isomeric 2,4-hexadiene~.~~~ a stepwise mechanism the 29 In intermediate diradical or dipolar ion may have a lifetime long enough for internal rotation to compete with ring closure. For example in the reactions of (20)with hexadienes (26-28) the cyclobutane products show stereoisomerisa- R jiF2 + CCl CF, II + CCI (2 8) R=Me or C1 29 L. K. Montgomery K.Schueller and P. D. Bartlett J. Amer. Chem. SOC. 1964,86 622. 150 A. Ledwith tion at that double bond which becomes part of the four-membered ring and not at the other one. Stereoquilibration is incomplete and allows a measurement of the competition between rotation and ring closure. The relative rates of these two competing processes were shown to be consistent with reasonable values assigned on the basis of known rotational barriers and known rate constants for the combination of analogous free radicals. In marked contrast to the diradical reactions of halogenated olefins cyclo- additions involving ketens display mechanistic features which in some in- parallel those to be expected for concerted processes (forbidden in this case) and at other times show evidence of dipolar reaction inter- mediates.30*31 Concerted cycloadditions normally have low enthalpies of activation (5-15 kcal.mole-') and very large negative entropies of activation (-25 to -45 e.u.).17 For the reaction between n-butylvinyl ether (29) with diphenylketen (30) to give cyclobutanone (31) the Eyring parameters in benzo- nitrile (31.4") were AH* 9.3 kcal.mole-l AS* -40 e.u. strongly suggesting that the addition was concerted.26 BUT Ph,C=C=O + (3--CH -H' Concerted cycloadditions yield products in which the cis tram-stereochemistry of the reacting double bond is completely retained. In agreement with this cri- terion Huisgen and his collaborators have demonstrated that cycloadducts of diphenylketen and dimethylketen with cis-and trans-propenylpropyl ether (MeCHSH-OPr) are formed with predominant retention of the olefin stereochemistry.28 On the other hand cycloadditions do not normally show regular dependence of rate on solvent polarity.For the reaction between (29) and (30)it was foundz6 that the rate varied linearly with solvent polarity para- meter ET,32although there was only a factor of 50 difference between cyclo- hexane and acetonitrile. Ths rate difference is very small however in com- parison with the corresponding rate ratio of 63,000 for the effect of changing from cyclohexane to acetonitrile for the stepwise cycloaddition of tetracyanoethylene (32) to p-methoxystyrene (33) (CN),C=C( CN) + p-MeO-C,H,-CHSH -+(CN),C-C(CN), II (32) (33) ArCH-CH 'O H.B. Kagan and J. L. Luche Tetrahedron Letters 1968 3093. 31 W. T. Brady and E. D. Dorsey Chem. Comm. 1968 1638. 32 K. Dimroth C. Reichardt T. Siepmann and F. Bohlman Annulen 1963 661 1. 33 D. W. Wiley personal communication quoted by R. Huisgen (ref. 26). Reaction Mechanisms 151 Because of the observed solvent dependence it can be shown26 that the transi- tion state for reaction between (29) and (30) must have a dipole moment greater than that (3.02 D) of the cyclobutanone product (31). Huisgen has suggested26 that all these observations may be rationalised by assuming that reactions of ketens with olefins are concerted but have transition states in which the two new bonds are not formed to the same extent and which have a considerable polarity e.g.(34). Woodward-Hoffmann rules’ would appear to be violated by this interpre- tation of the reaction mechanism and Huisgen has indicated briefly28 how this may be overcome by theoretical reasoning. Full details of the theoretical treat- ment are eagerly awaited especially since there is clear evidence of a two-step procesi for the related cycloadditions of diphenylketen (30) with benzylidene- aniline3’ (35) and with carbodi-imide~~’ (36). PhCH=N-Ph + Ph,C=C===O + PhCH=NPh (35) + I * Ph6H-Tph I I PhEM‘ H-NPh PhCH-NPh A‘ PhZCH-Phz -C=O (37) (39) A particular feature of both the latter reactions is that the dipolar intermediates may be trapped by addition of water or methanol to yield stable adducts (37) and (38) differing from the cycloadducts (39) and (40).3 + 2 -+ 5 Reactions. Cycloadducts of diazoalkanes [e.g. (15)] have been known many years but it was not until the early 1960’s that the classification ‘lY3-dipolar cy~loaddition’~~ 35 became generally accepted. This followed a series of outstanding studies by Huisgen and his collaborator^^^ in which diazoalkanes were shown to represent just one example of a wider class of 1,3-dipolar molecules (abc) which undergo 1,3-cycloadditions and are des- cribed by zwitterionic octet structures e.g. 34 R.Huisgen Angew. Chem. Internat. Edn. 1963,2 565. 35 R. Huisgen. Angew. Chern. Internat. Edn. 1963,2 633. 152 A. Ledwith + +-+-a=b -c i-+a = b = c (b = N) +-+ a = b -~+-+a -b = c (b = NRorO) +-Specific classes of molecular 1,3-dipoles include diazoalkanes (R,C=N=N) nitrile oxides (Arc=&-0) azides (ArN=k=N) nkrones (ArCH=N+ Me- +-0),nitrile imines (ArC=N-N-Ar) sydnones (fkN=CR-CO-0-N) and a great many others.1,3-Dipolar cycloadditions exhibit common mechanistic features :36 they are not markedly influenced as to rate or stereochemistry by solvent polarity they show low enthalpies of activation (5-15 kcal. mole-l) and large negative entropies of activation ( -25 to -45 e.u.) they produce five-membered cyclic compounds in which the stereochemistry of the reacting olefin (dipolarophile) is maintained and finally reaction rates are markedly increased by conjugation of the reacting site in the dipolarophile but reduced by the steric effect of all types of substituent.The synthetic value of 1,3-dipolar cycloadditions has been extensively reviewed by H~isgen,~~ and full experimental details of his nitrile and sydnone~~~ work with nitr~nes,~~ has now been published. Other recent synthetic developments involve use of fluorinated diazoalkanes3' (41) and vinyl diazomethane4' (7) and the formation of high polymers from a variety of 1,3-dipole~.~' For the first time since the conception of concerted dipolar cycloadditions by H~isgen,~~ the reaction mechanism has been challenged in a reasoned and stimulating manner by Fire~tone.~~ Basically the dispute between Fire- stone4 and Hui~gen~~?~~ relates to whether a two-step or concerted addition mode is demanded by experimental observations i.e.jb R. Huisgen R. Grashey H. Hauck and H. Seidl Chem. hr. 1968,101 2043. 3'7 M. Christl and R. Huisgen Tetrahedron Letters 1968 5209. 38 R. Huisgen H. Gotthardt and R. Grashey Chem. hr 1968 101 536; R. Huisgen and H. Gotthardt ibid. pp. 552 1059. 39 J. H. Atherton and R. Fields J. Chem SOC.C,1968 1507. 40 G. Manecke and H. U. Schenck Tetrahedron Letters 1968,2061. 41 J. K. Stille and L. D. Gotter J. Polymer Sci. 4 1968 6 11. 42 R. A. Firestone,J. Org. Chem. 1968,33,2285. 43 R. Huisgen J. Org. Chem. 1968,33,2291. Reaction Mechanisms 153 CH2-CH CF3.CHN + CH2==CH2 I I F3C-CH N .-yq+ (41) R1 R2 +-3, CH,=CH-CH=N=N + R1C=CR2 + c CH N 1\N/ CH I CH2= CH 11 H CH i b ad \c-concerttda/ \c Huisgen I mechanism d===e !\ \,b a c-/ Firestone mechanism d-e.(42) Firestone suggests that the observed independence of rate on solvent polarity is better explained by assuming diradical intermediates (42) as indicated. The observed stereospecific addition would then arise because the energy barrier to rotation around the bond d-e in the diradical(42) is much greater than the activation energy for ring closure or for reversion of (42) to the react- ants. Thus all biradicals (42) which are not formed in the correct conformation for ring closure will revert to starting materials. As noted by Hui~gen,~~ however this premise is in marked contradiction to the high degree of stereo- equilibration observed24 in very similar diradical intermediates formed during reaction of (20) with hexadienes (26-28) (see previous section).Nevertheless workers in other fields44 have previously demonstrated (by calculation) that in free radical polymerisation of methyl methacrylate radicals such as (43) 21' it' -CH2 -CH2-* &O,Me AO,Me (43) have very high barriers to rotation around the CH,-C bond so much so that rotation is energetically less favourable than reaction of the free radical with another molecule of methyl methacrylate. Since similar radicals would be 44 C. E. H. Bawn. W. H. Janes and A. M. North J. Polymer Sci. C 1963.4 427. 154 A. Ledwith involved in dipolar additions via the Firestone mechanism the suggestion that ring closure of diradicals is more rapid than bond rotation would have independent support for at least some systems.If diradical intermediates were involved in 3 + 2 cycloadditions it would be anticipated that the reactivity of typical dipolarophiles towards free radicals would parallel their reactivity in cycloadditions. From studies on copolymerisation of n-butyl maleimide (44;R = Bun) and maleic anhydride (45) with methyl metha~rylate~~ it can CH=CH CH=CH Lo Lo Lo Lo \/ N ‘O/ R (44) (45) be deduced that the double bond in the maleimide is at least one order of magnitude greater in reactivity than that in the anhydride. N-arylmalemides are even more reactive.46 The Firestone mechanism predicts therefore that N-phenylmaleimide should be more reactive than maleic anhydride towards a common 1,3-dipole as found e~perimentally~~ for reactions with aryl +-azides (ArN=N=N).On the other hand for reactions with diphenyl diazo- methane (Ar,C=N=N) maleic anhydride displays a higher reactivity than maleimide N-methylmaleimide or N-~henylmaleimide,~’ arguing against radical intermediates. Firestone suggests4’ that transition states for 3 + 2 dipolar cycloadditions should be coplanar [e.g.(46)]and not having ‘two planes’ [e.g. (47)] as required for an orbital symmetry-allowed concerted process.43 The ‘two planes’ orientation complex (47) was proposed by Hui~gen~~ before orbital symmetry conservation had been recognised as a controlling factor in 45 G. E. Ham ‘Copolymerisation,’ Interscience London 1964. 46 R. C. P. Cubbon Polymer 1965,6,419.‘’ A. Ledwith and A. C. White. unpublished results. Reaction Mechanisms concerted organic reactions and is amply supported by the well established reactivity of sydnones (48) in 1,3-dipolar cycloadditions. Sydnones (48) are R C planar aromatic molecules and only an orientation complex such as (49) is possible. Consideration of the electron distribution in (47) shows that the 1,3-dipolar addition involves interaction of a 4x-electron system with a 2x-electron system-as in the Diels Alder reaction. All aspects of 1,3-dipolar cycloadditions have been surveyed in a spirited defence of the concerted mechanism by H~isgen,~’ although it was admitted that the question of orientation i.e. whether /b\ /b\ a C a C I I I Or I7 d---e e d is not adequately predicted by either concerted or diradical mechanisms.For ths author the experimental evidence points clearly to the Huisgen concerted mechanism for 3 +2 cycloadditions but the challenge by Firestone should stimulate much activity in this area and is all the more welcome. NC CN 6 0 C-C \/ +(NC),C_/\C(CN) *(NC,? \C(CN) NC/\/‘CN 0 (51) 156 A. Ledwith Tetracyanoethylene oxide (50) reacts as a 1,3dip0le,~* via a so called ‘active form’ (51) which may be diradical or dipolar in nature to give mainly tetra- cyano tetrahydrofurans [e.g. (52)l. Although the reaction is one of the most fascinating of 3 + 2 cycloadditions with electron rich olefins and condensed aromatics (2,3-dihydropyran anthra- cene) there is a side reaction involving oxygen transfer e.g.The relative importance of dipolar addition and oxygen transfer has been surveyed by Brown and Cook~on.~’ A novel 1,3dipole has recently been characterised by Turro and his col- laborator~,~~ stimulated by the predictions of Woodward-Hoffman rules. By analogy with ‘active’ tetracyanoethylene oxide (5l) cyclopropanones (53) should react as 1,3dipoles (54) giving rise to concerted 3 + 2 + 5 cyclo-additions or as allylic cations (see later) yielding 3 + 4 + 7 cycloadditions. The former possibility was confirmed for the reaction of chloral (55) with 2,2-dimethylcyclopropanone (53). 0 0-+ \p7 (53) (54) 4 + 2 + 6 Reactions. Diels-Alder cycloadditions are the most important of all cycloadditions and are correctly classified under this heading.From time to time there have been many attempts to explain the stereospecificity lack of clearly defined solvent dependence absence of catalysis etc. by other than a concerted addition process but after carefully considering all the evidence 48 W. J. Linn and R. E. Benson J. Amer. Chem. SOC.,1965,87,3651. 49 P. Brown and R. C. Cookson Tetrahedron 1968,24,2551. N. J. Turro S. S. Edelson J. R. Williams and T. R. Darling J. Amer. Chem. SOC 1968 90 1926. Reaction Mechanisms available Sauer21 was led to favour strongly the concerted mode. The con- certed mechanism is allowed by Woodward-Hoffman rules as a thermal process but forbidden photochemically. Bryce-Smith and Gilbert’ have recently reported an apparent striking exception to these rules.Addition of trans-stilbene to tetrachloro-o-benzoquinoneat 120” gave exclusively the trans-[4 + 21 adduct (56). Photochemically the same reagents reacted in benzene at 15” (under nitrogen) to give 88% of trans- (56) and only 12% of the corresponding cis-isomer (57). It was concluded that although the photoreaction was a two-step process steric control was similar to that in the concerted mode of addition because of dipolar resonance forms of the singlet diradical intermediate (58). It is highly likely that this interesting observation in a 4 + 2 system is directly related to the ‘forbidden’ concerted 2 + 2 reactions of ketens26-28 discussed in the preceding sections and also to the effect of solvent polarity in orientation in some 2 + 2 photochemical reactions.” 4 + 3 Reactions.Cycloaddition reactions of allylic cations with dienes have recently been demonstrated by Hoffman and J0y.53954 In general terms the reaction may be represented as 0 Electron distribution in the transition state relates to that of the tropylium cation in a manner analogous to the relationship between states for Diels-Alder reactions and benzene. ’’ The experimental approach and typical products are adequately described by the following Scheme.53 D. Bryce-Smith and A. Gilbert Chem. Comm. 1968 1701. ” B. D. Challand and P. de Mayo Chem Comm 1968 982. 53 H. M. R. Hoffman and D. R. Joy J. Chem SOC.(B) 1968 1182. s4 H. M. R. Hoffman D. R. Joy and A. K.Suter J. Chem. SOC.(B) 1968 57. ” M. G. Evans 7’rans.Faraday SOC. 1939,35 824; M. G. Evans and E. Warhurst ibid. 1938,34 614. 158 A. Ledwith solvent-separated ion-pair chair-like T.S. CH, / \ 0 SCHEME Cycloaddition of allylic cations could become an important synthetic route to cycloheptane derivatives. Consequently the need to devise reaction conditions which will permit cycloaddition rather than simple cation addition presents a stimulating area for further development. Cationic polymerisation of diene~~~ is normally considered to involve a mixture of 1,2-and 1,4-addition processes e.g. + + R + CH,--CH.CH=CH + RCH,-CH-CH=CH, 1 C4H6 RCH,-CH=CH-CH,-CH,-CH-CH-rH + RCH,-CH-CH=CH, I+ CH,-CH-CH=CH 56 W. Cooper “The Chemistry of Cationic Polymerisation,” ed P.H. Plesch Pergamon London 2-coCCI Reaction Mechanisms 159 Conditions under which cationic polymerisations are made involve solvents of low dielectric ion-pairing of propagating cations complex ion-pairs formed from Lewis acid catalyst fragments and low temperatures. It seems to the author that conditions for cycloaddition of allylic cations will exist during polymerisation of dienes and might explain the well established deficiency in double bond content of the polymers.56 Plausible intermediates would be similar to (59) and (60).Recent studies of cationic polymerisation of diene~~~ have established the presence of saturated six-membered rings in the polymer chain and mechanisms have been suggested for their formation.In the light of the experimental results of Hoffman and 54 a reinterpretation of both polymer structures and reaction mechanism may be necessary. CH;CH*CH= CH (6 0) Carbenes.-During the past 15 years previously uncharacterised divalent carbon derivatives have become commonplace intermediates in a wide variety of useful organic reactions.58’ 59 This enormous growth in interest and applica- tion stems very largely from pioneering work of the research groups led by 1963 p. 351. 57 N. G. Gaylord I. Kossler and M. Stolka A.C.S. Polymer Preprints 1968 9 No. 2 p. 1254; N. G. Gaylord 1. Kossler M. Stolka J. Vodehnal J. Polymer Sci. 1964 A2 3969; B. Matyska K. Mach J. Vodehnal and I. Kossler Coll. Czech. Chem. Comm. 1965 30 2569; N.G. Gaylord B. Matyska K. Mach and J. Vodehnal J. Polymer Sci. 1966 Al 4 2493. 58 W. Kirmse “Carbene Chemistry,” Academic Press London 1964. 59 ‘4.Ledwith “The Chemistry of Carbenes,” R.I.C. Lecture Series of Monographs. 1964. No. 5. 160 A. Ledwith Doering6’ and Skel16’ during the early 1950’s. Carbenes are generated by two main types of reaction (a) photolysis or thermolysis of reactive molecules such +-as diazoalkanes (R,C=N=N) and ketens (R,==C==C=O) and (b) 1,l-elimination (frequently base-induced) from molecules R,CXY where X and Y are halogens. Considering carbene (CH :) as the simplest example the presence of four low-energy bonding orbitals on the carbon atom automatically makes it an electron-deficient species. Two orbitals are used for bond formation with the hydrogen atoms leaving two orbitals for occupation by the remaining two non-bonding electrons.In triplet carbene the two non-bonding electrons are unpaired in degenerate orbitals whereas in singlet carbene these electrons are paired. Spectroscopic studies62 suggest that carbene has a linear triplet ground state which in the gas phase is rapidly formed by collisional quenching of the initial higher energy bent singlet state. In the liquid phase singlet carbene reacts essentially on collision with its nearest neighbour molecules giving rise to random insertion and addition products. Carbenes have been shown to react with C-H 0-H N-H S-H C-Cl C=C C=O C=N and CkC bonds but apart from the obvious synthetic value of these reactions mechanistic studies in carbene chemistry centre on correlation of reactivity and stereochemistry with the spin multi- plicity and excess energy content of the divalent carbon unit.58* 59 63 In addition the correlation between geometrical structure and spin multiplicity of carbenes has been of great interest to theoretical chemists.The electronic structures of carbenes have recently been discussed at length by Hoffman Zeiss and Van Dine.64 Extended Huckel calculations were used to predict geometries of lowest singlet and triplet states. Some of this work has also been included in a timely review by C10ss~~ whch comprehensively surveys carbene structures and the stereochemistry of 2 + 1 carbene cycloadditions. From a consideration of the early experimental results Skell proposed6’ that singlet carbenes react stereospecifically with ethylenic bonds and insert directly into carbon-hydrogen linkages.Triplet carbene on the other hand should react with alkanes by a typical radical abstraction process and yield isomerised products from cis trans-olefins. Skell further concluded that singlet carbenes were electrophilic reagents and would thus react with olefins in a manner similar to that of carbonium ions resulting in an unsymetrical n-approach of the vacant carbene orbital i.e. (62) rather than the more symetrical approach (61). It is significant 6o W. von E. Doering and A. K. Hoffmann,J. Amer. Chem. SOC.,1954,76,6162;W. Von E. Doering and L. H. Knox ibid. p. 4947. 61 P. S. Skell and R.C. Woodworth J. Amer. Chem SOC.,1956,78,4496;P. S.Skell and A. Y.Garner ibid. p. 3409. G. Hertzberg Proc. Roy. SOC. 1961 A262,291; G. Hertzberg and J. W. C. Johns ibid. 1967 A295,107. 63 H. M. Frey. Prop. Reaction Kinetics. 1964. 2. 131 W. Kirmse. Angew Chem. Internal. Edn. 1965 4 1; G. Kobrich ibid. 1967 6 41. 64 R. Hoffman G. D. Zeiss. and G. W. Van Dine. J. Amer. Chem. SOC..1968.90 1485. 65 G. L. Closs “Topics in Stereochemistry,” ed. N. L. Allinger and E. L. Eliel Interscience 1968 vol. 11 p. 193. Reaction Mechanisms therefore that this early intuititive prediction is fully borne out by theoretical calculations and construction of level and state correlation diagrams.66 \ 1 ' ' =< ,C =c =c top view 'C=C / / I' However it is now suggested66 that singlet carbene ('A ') adds stereospecifically not because it is a singlet but because it can correlate with the lowest singlet configuration of a trimethylene and thus with the ground state of a cyclo- propane.Triplet carbene (3B,) adds non-stereospecifically not because it is a triplet but because its complex with a ground state ethylene must correlate with a triplet state of an excited configuration of the trimethylene one in which there are no barriers to rotation around terminal bonds. Symetrical addition of singlet carbene is allowed provided that the carbene is in an excited linear c~nfiguration.~'Calculations and spectroscopic information place the lowest linear singlet of carbene ('Ag) between 10 and 20 kcal. mole-' above the lowest bent singlet ('A').Reacting carbene generated by photolysis (3660 A) of diazomethane is estimated68 to carry approximately 15 kcal. mole-' excess energy. Consequently photolysis of diazomethane could produce excited linear singlet carbene ('Ag) and hence react stereospecifically with olefins oia a symetrical approach.67 Further theoretical consideration of carbene struc- tures has led to the conclusion69 that singlet ground states are to be expected when the carbene carries a substituent having high-energy occupied orbitals [e.g. :CF, :CCl, :C(NR,),] or when it is conjugated with a polyene system having the aromatic grouping of (4n + 2) x-electrons (e.g. cyclopropenediyl or cyclo heptatrienedi yl). Photolysis of diazomethane or keten in the gas phase yields a mixture of singlet and triplet carbene and permits simultaneous investigation of their relative reactivities." Work in this area continues unabated ; carbene from " R.Hoffman J. Amer. Chetn. Soc. 1968 90 1475. " A. G. Anastassiou Chrni. Conini. 1968 991. 68 H. M. Frey ref. 58 p. 221. 69 R. Gleiter and R. Hoffmann. J. Amer. Chem. SOC.. 1968,M. 5457. lo J. A. Bell Progr. Phys. Org. Chem. 1964,2,1; W. B. de More and S. W. Benson Adti. Photochrm.. 1964 2. 219. 162 A. Ledwith photolysis of diazomethane reacts with cyclobutene7 to give (initially) (63)444). The cyclobutane derivatives (63H65) are thought to arise from singlet carbene and undergo further isomerisation (because of excess of vibrational energy) to a mixture of olefins.Vinylcyclopropane (66) is thought to be the major product of reaction with triplet carbene. Gas phase reaction of carbene with alkyl ethers has e~tablished~~ that singlet carbene inserts into the various C-H bonds in random fashion whereas triplet carbene reacts predominantly at the C-H bond alpha to the oxygen atom. With methyl alkyl ethers singlet carbene appears to undergo a displacement reaction producing dimethyl ether and an olefin. By use of nitrogen-15 it has now been demonstrated that carbene (from a variety of precursors) reacts with nitrogen to regenerate diazomethane.’ Photolysis of keten in hydrogen gives rise to a chain reaction in which methane ethane and ethylene are produced.74 From a detailed kinetic analysis it was concluded that methane is not formed by a direct insertion process.The gas phase reactions of triplet carbene with simple alkanes have been studied in detail by Ring and Rabin~vitch.’~ Primary secondary and tertiary C-H bonds undergo hydrogen abstraction by triplet carbene at the relative rates 1:14 150. The same C-H bonds react with triplet methylene by insertion at the relative rates 1 :2 7. Addition of 3CH2 to the double bond in ethylene occurs 3.5 times faster than abstraction from a tertiary C-H bond. For abstraction from primary C-H 3CH2 shows a primary kinetic isotope effect k,/k = 3.9 whereas insertion by 3CH2 into the same bond shows kH/kD = 2. Reaction between carbene (from photolysis of keten) and ethyl chloride appears to occur exclusively by a radical chain process involving the following abstraction reactions.76 :CH2 + CH,.CH,Cl+ CH2C1 + CH3.CH2* :CH + CH3.CH,C1+ CH,. + *CH2*CH2Cl :CH2 + CH3*CH2C1-+ CH3*+ CH3*cHCI ” C. S. Elliott and H. M. Frey Trans. Faraday SOC. 1968 64 2352. 72 H. M. Frey and M. A. Voisey Trans. Faraday SOC. 1968,64 954. 73 A. E. Shilov A. A. Shteinman and M. B. Tjabin Tetrahedron Letters 1968,4177. ” J. W. Powell-Wiffen and R. P. Wayne Photochem. and PhotobioL 1968,8 131. 75 D. F. Ring and B. S. Rabinovitch Canad. J. Chem. 1968 46 2435. ’‘ C. H. Bamford J. E. Casson and A. N. Hughes Proc. Roy. SOC. 1968 A306 135. Reaction Mechanisms All the expected radical combination and disproportionation products were identified and from the effect of added diluents (N and CO) it was concluded that singlet carbene abstracts chlorine preferentially whereas triplet carbene discriminates in favour of hydrogen abstraction.Singlet fluorocarbene (:CFH)77 and chlorocarbene (:CHC1)78 are formed by recoil reactions of energetic tritium atoms with CH,F and CH,Cl respectively. CH2X2+ T* -+ [CHTX,*] + :CTX + HX Both :CHF and :CHCl react stereospecifically with cis-and trans-but-2-ene but do not insert into C-H bonds. Similar reduced activity of :CHC1 over :CH was previously reported for liquid phase reactions of :CHCl generated by photolysis of chlorodiazomethane.79 Phenylcarbene (PhCH :) may be generated by photolysis of three different precursors (67-69)80 but the relative rates of insertion into the various C-H (iii ) H Ph .yak H Ph (67) (68) linkages of n-pentane are independent of precursor.It was concluded therefore that the initially formed singlet PhCH is rapidly equilibrated to a common vibrational level prior to reaction with the alkane. Phenylcyanocarbene (PhC-CN)81 is produced on photolysis of the oxiran (70) but a more efficient and simpler preparation involves photolysis of the 1,3,2-dioxaphosph(v)olan (71).81 This particular carbene is novel in being a canonical form of the nitrene (73) and is also produced by photolysis of the aide (72).81 -N* PhCd-N -PhCg-N +-+ PhC-C=N l7 Yi-Noo Tang and F. S. Rowland J. Am. Chem. SOC. 1967,89,6420. YI-NooTang and F. S. Rowland J. Amer. Chem. SOC. 1968,90 574. 79 G. L. Closs and J.J. Coyle J. Amer. Chem. SOC.,1962,Sq 4350; 1965,87,4270. *' H. Dietrich G. V. Griffin and R. C. Petterson Tetrahedron Letters 1968 153. P Petrellis and G W Griffin Chem Comm . 1968. 1099 E. Schmitz Angew. Chem. 1964 76 197; H. M. Frey and 1. D. R. Stevens Proc. Chem. SOC. 1362. 79; J. Amer. Chem. SOC. 1962,84 2647. 164 A. Ledwith Diazirines are isomeric forms of diazoalkanes and may be used as carbene precursors although not so conveniently as the corresponding diazoalkane. 82 It has now been reported83 that phenylbromodiazirine is a particularly convenient (photochemical) source of phenylbromocarbene (PhCBr) and photolysis of the diazirine in olefins gives essentially quantitative yields of cyclopropanes with retention of configuration.Thermal decomposition of bromodichloromethylphenylmercury (PhHgCBrCl,) in refluxing benzene has proved to be one of the most convenient method for generating dichlorocarbene. 84 The corresponding mercurial PhHgCC1,F reacts in a similar manner to generate chlorofluorocarbene in the most convenient synthesis yet reported for this reactive intermediate.85 A new synthesis of unsaturated carbenes 86 [e.g. (75)] involves the reaction of bases with nitro-oxazolidinones (74). The corresponding unsaturated diazo- alkane is first formed and the carbene demonstrated to be an intermediate by trapping with cyclohexene or alkyl vinyl ethers. Carbenes and carbonium ions may be regarded as base and conjugate acid respectively i.e. R,C + H+ f R2CH+ Recently a novel and most interesting carbene synthesis has been developed (MeS),kH BF h(MeS),C (76) (MeO),kH BF; a(Me0)2C (77) 83 R.A.Moss Tetrahedron Letters 1967,4905. 84 D.Seyferth and J. M. Burlitch J. Amer. Chem. SOC.,1963,85 2667. 85 D.Seyferth and K. V. Darragh J. Organometallic Chem. 1968,11 9. 86 M.S.Newman and A. 0.M. Okorodudu J. Amer. Chem. SOC. 1968,90,4189. Reaction Mechanisms 165 based on tlus eq~ilibrium.~~ The stable cations (76 and 77) were treated with bases to yield corresponding bisalkylthio- and dialkoxy-carbenes. Neighbouring group participation is now well documented as a contributing factor in the formation and reactivity of electrophilic reagents particularly carbonium ions.88 In a recent publication Robson and Shlechtersg have reported perhaps the first clear case of a similar phenomenon during rearrange- ment to a divalent carbon species.Thermolysis of diazolkanes (78) yields beta-substituted styrenes (79) by rearrangement of initial carbene fragment. A ArIz-CH,X rN+ Are-CH,X +ArCH==CHX 2 (78) (79) X = OMe or NMe In contrast the corresponding mercapto-derivative (80) yields a carbene which rearranges by exclusive (SEt) shift to give the corresponding alpha-substituted styrene (82) A -+ ArC-CH,.SEt + -N2 (80) The authors suggest that increased migratory aptitude of RS (over RO and R2N)results from an 'ylide' transition state (81) involving 3d orbitals of sulphur. Many years ago Chattgo suggested that the adduct of ethylene with platinous chloride was a methylcarbene complex of platinum e.g.[CH,-CH :PtClJ-. Later work made this proposal untenable and led to the presently accepted theory of metal-olefin complexes.9' At that time carbenes were not recognised as reaction intermediates but recent workg2 has shown that carbene-metal complexes may be obtained having a structure similar-to that originally suggested by Chatt.go Carbenes of the type MeOCR and HOCR form crystalline derivatives with carbonyl derivatives of chromium tungsten molybdenum and manganese e.g. Ph(Me0)C :W(CO), Ph(Me0)C :Cr(CO), R(Me0)C Mn(C,H,)(CO),. Crystal structures for some of these complexes have been determinedg3 and it is interesting that for Ph(Me0)C :Cr(CO) the carbene unit is bent with a Ph-C-OMe angle of 104".This compares favourably with the value of 103"for the corresponding angle in singlet carbene.62 '' R.A. Olofson S. W. Walinsky J. P. Marino and J. L. Jernow J. Amer. Chem. SOC. 1968,90 6554. B. Capon Quart. Rev. 1964,28 45. *' J. H. Robson and H. Shechter J. Amer. Chem. SOC. 1967,89 7112. J. Chatt Research 1951 4 180. J. Chatt and L. A. Duncanson J. Chem SOC.,1953,2939. " E. 0.Fischer and A. Riedel Chem Ber. 1968 101 151. 93 0.S. Mills and A. D. Redhouse J. Chem. SOC.(A) 1968 642. 166 A. Ledwith Nitrenes.-Nitrenes (RN :) are isoelectronic with carbenes (R,C :) but have only been recognised as discrete intermediates since the early 1960’s. Like carbenes they possess close-lying singlet and triplet electronic states which control their reactivity.For example singlet ethoxycarbonylnitrene (EtOCON :) undergoes selective and stereospecific insertion into C-H bonds producing amines and adds stereospecifically to olefins to give aziridines. Triplet ethoxy- carbonylnitrene however does not undergo insertion into C-H bonds and adds to olefins with complete loss of the geometric c~nfiguration.’~ Carbenes are generated by photolysis of diazoalkanes (R,CN,)58v 59 and by analogy nitrenes are most conveniently obtained by photolysis of azides (RN,). 94 Similarity between carbenes and nitrenes is most marked in their carbonyl derivatives. Carbonylcarbenes are produced from diazo-ketones and yield ketens by concerted (Wolff) rearrangement. Similarly nitrenes from carbonyl azides yield isocyanates by concerted (Curtius) rearrangement,94 e.g.RCO-CHN -RCO*CH -RCH=C=O -N RCON3 -RCO-N -RN=C=O -N For pivaloylnitrene (83),95 rearrangement to t-butyl isocyanate (84)competes favourably with trapping of the nitrene by cyclohexene Me,C.CON Me,C.CON + Me,C-N=C=O (83) (84) (45 %) Aromaticg6 and heterocyclicg7 nitrenes readily undergo ring contraction to the corresponding nitrile e.g. Cyanonitrene (NCN) is generated by thermolysisg8 or photolysisg9 of solutions of cyanogen azide (N,CN). The rules of spin conservation demand 94 W. Lwowski Angew Chem. Internut. Edn. 1967,6 897. 95 G. T. Tisue S. Linke and W. Lwowski J. Amer. Chem. SOC.,1967,89,6303. 96 E. Hedaya M. E. Kent D. W. McNeil F. P. Lossing and T. McAllister Tetrahedron Letters 1968,3415.97 W. D. Crow and C. Wentrup Chem. Comm. 1968 1082 1026. 98 A. G. Anastassiou and H. E. Simmons. J. Amer. Chem. SOC.. 1967.89 3177. 9y H. W. Kroto J. Cheni. Phys. 1966 44 831. Reaction Mechanisms that initially produced cyanonitrene should be in a singlet electronic (excited) state but there has been some confusion over this point since irradiation of N3CN through a Pyrex filter was reported"' to give triplet cyanonitrene. A more recent and detailed investigation of the photolysis of cyanogen azide in the presence of cis-and trans-1,2-dimethylcyclohexane(insertion into the tertiary C-H bonds) has now demonstrated unambiguously that photolysis of cyanogen azide with light ranging from 2100 to 3000 A produces exclusively singlet NCN.''l The earlier results had led to a suggestion1" that the 2750 8 band in the spectrum of N3CN represents a singlet-to-triplet transition and hence photolysis with light of this wavelength yielded triplet NCN directly- a conclusion now shown to be erroneous.1o1 Further studies with cyanogen azide have shownlo2 that three distinct processes occur during thermal reaction with cyclo-octatetrarene (cot).These are a bimolecular reaction leading to alkylidenecyanamide (85) a 2 + 1 cycloaddition of singlet cyanonitrene yielding aziridine (86) and 4 + 1 (stepwise) cycloaddition of triplet cyanonitrene yielding the adduct (87). N3CN cot c -N cot NCN I collisional deactivation I A major difference between carbenes and nitrenes is that the latter readily undergo collisional deactivatioii from excited singlet states to ground triplet states in solution.Consequently there are marked solvent effects on products arising from reactions of nitrenes according to the relative rates of solvent loo L. J. Schoen J. Chem. Phys. 1966,45 2773. lo' A. G. Anastassiou and J. N. Shepelavy J. Amer. Chem. SOC.,1968,90 492. A. G. Anastassiou,J. Amer. Chem. SOC.,1968. 90.1527. 168 A. Ledwith deactivation to triplet electronic states and direct (stereospecific) insertion and addition reactions of the singlet state. Io3 Beckwith and Redm~ndl"~ have evaluated these effects for reactions between ethoxycarbonylnitrene with cis-and trans-but-2-ene. It was found that solvent deactivation of singlet EtO CON was temperature-dependent with an activation energy greater than that for stereospecific reaction with the olefin.In a similar study using anthracene,lo5 the same authors demon- strated a dichotomy of mechanism involving direct substitution (b)with triplet nitrene and intermediate aziridine formation (a)from the singlet derivative. NH*C02 Et a-@JJ \ // H The nature of the stereospecific insertion reactions of nitrenes into C-H bonds continues to be of some interest. A detailed investigation of the reactivity of ethoxycarbonylnitrene towards the various positions of cyclohexane norbornane bicyclo[2,2,2]octane and adamantane led to the conclusionlo6 that both free-radical and nitrene insertion reactivities are governed similarly by structural variations.Benzene reacts with singlet methylsulphonylnitrene to give mainly the sulphonamide (88). Detailed studies by Abramovitch and Uma107 have established that the reaction involves equilibrating intermediates (89) and (90) and a minor product (91). At 120" the reaction yields predominantly (88) via (90). The azepine (91) was trapped (in low yield) as an adduct with tetra- cyanoethylene. '03 J. H. Hall J. W. Hill and J. M. Fargher J. Amer. Chem SOC.,1968,W 5313; A. Mishra S. N. Rice and W. Lwowski J. Org. Chem. 1968,33,481;J. E. Baldwin and R. A. Smith ibid. 1967,32,3506. A. L. J. Beckwith and J. W. Redmond J. Amer. Chem SOC. 1968,90 1351. lo5 A. L. J. Beckwith and J. W. Redmond Chem Comm. 1967 165. lo6 D.S. Breslow E. I. Edwards R. Leone and P. von R. Schleyer J. Amer. Chem. SOC. 1968,90 7097. R. A. Abramovitch and V. Uma Chem. Comm. 1968 797. Reaction Mechanisms 169 0"'"""'"' Nitrenes appear likely to become important synthetic intermediates as demonstrated recently lo8 by the reaction between porphyrins and ethoxy- carbonylnitrene (as shown on p. 170). Aziridines formed by reaction of nitrenes with olefines frequently isomerise to open chain amines during the reaction. With the aminonitrene (92)"' stable a'ziridines are formed by (stereospecific) reaction with a variety of olefins. A main difficulty when using nitrenes as synthetic intermediates lies in the elevated temperatures required to decompose the organic azide precursor.It is highly significant therefore that Dekker and Knox'" report that nitrenes result from metal carbonyl-catalysed decomposition of several precursors. Thus nonacarbonyldi-iron reacts rapidly at room temperature with azido- benzene methyl isocyanate and nitromethane to give the complex adducts (93H95) respectively. (co)~ ,Me\\\//./;;, /Fe (CO) 0 :grR R\yX > /R (CO),Fe --.Fe(CO) (CO)$e--(93) (C0)ff Fe(CO)3 (94) Me' (95) There would be obvious synthetic potential if this type of catalysis could be modified to allow trapping of the nitrene by independent reactants. lo' R. Grigg Chem. Comm. 1967 1238. log R. S. Atkinson and C. W. Rees Chem. Comm. 1967 1230. 'lo M. Dekker and G. R. Knox Chem. Comm. 1967 1243. 170 A.Ledwith

ISSN:0069-3030    

DOI:10.1039/OC9686500143

出版商:RSC    

年代:1968

数据来源: RSC

摘要:

4 FREE-RADICAL REACTIONS By M. J. Perkins (Department of Chemistry King’s College Strand London W.C.2 ) THISis the first Annual Report for several years in which the organic chemistry of free radicals has been allocated separate space.’ In view of this and the independent publication recently of an annual survey of free-radical reactions which valiantly strives after comprehensive coverage as a prime objective,* it seems apposite to include in the present review some of the more significant developments in the subject during the past 2-3 years. The discussion will be restricted almost entirely to results obtained in the liquid phase. The enormous volume of research publication in this field has recently been paralleled by the growth of an extensive review literature and numerous books3 and reviews4 have appeared during 1968.One of the outstanding problems in radical chemistry concerns the preferred geometry of alkyl radicals. The bulk of experimental data can be accommodated equally well by a planar structure or by one which is pyramidal but rapidly inverting. One approach to this problem has been to investigate the ease of production of bridgehead radicals in cage molecules. For example from a ’ See G. H. Williams Ann Reports 1958 55 156. See B. Capon M. J. Perkins and C. W. Rees ‘Organic Reaction Mechanisms 1965 1966 and 1967,’ Interscience London and New York 1966 1967 and 1968. ‘Advances in Free-radical Chemistry’ ed. G. H. Williams Logos and Academic Press London and New York 1968 vol. 3; A. R.Forrester J. M. Hay and R. H. Thompson Organic Chemistry of Stable Free Radicals,’ Academic Press London and New York 1968; ‘Oxidative Coupling of Phenols,’ eds. W. I. Taylor and A. R Battersby M. Dekker New York 1967; ‘Yuriki no Kagaku’ (Chemistry of Free Radicals) eds. H. Sakurai and K. Tokumaru Nankodo Tokyo 1967; ‘Radical lons,’ eds. E. T. Kaiser and L. Kevan Interscience New York 1968; ‘Organosulphur Chemistry,’ ed. M. J. Janssen Interscience New York 1967; ‘Oxidation of Organic Compounds-1,’ ed. R. F. Gould Advances in Chemistry Series 75 Amer. Chem. SOC. Washington 1968. Introductory Review W. A. Pryor Chem Eng. News Jan. 15 1968 p. 70; Study of Reaction Intermediates by E.S.R. Proc. Roy. SOC. 1968,302 A 287-361; see also G. A. Russell Science 1968 161 423 N.M. Atherton Science Progr. 1968 56 179 Y. S. Lebedev. Uspekhi Khimii 1968 37 934 F. Gerson Chima 1968,22,293 and C. Thompson Quart. Rev. 1968,22,45; Aromatic Substitu- tion D. H. Hey Bull. SOC.chim. France 1968 1591; Radical cyclisation M. Julia and M. Maumy ibid. p. 1603; Reactions of Alkoxy Radicals C. Walling ibid. p. 1609 and K. Heusler Chimia 1967 21 557; Radical Ions M. Szwarc Prog. Phys. Org. Chem. 1968 6 323; Aromatic Radical Anions P. Rempp Bull. SOC. chim. France 1968 1605; Phenoxyl Radicals V. D. Pokhodenko V. A. Khiznyi and V. k Bidzilya Uspekhi Khimii 1968 37 998; Aspects of Autoxidation F. R. Mayo Accounts Chem. Research 1968; 1 193; Photolysis of Aryl Iodides R. K. Sharma and N. Kharasch Angew. Chem. Intern Ed. 1968 7 36; Anode Processes B.E. Conway Pure Appl. Chem. 1968 18 105 N. L. Weinberg and H. R Weinberg Chem. Rev. 1968 68 449 A. K. Vijh and B. E. Conway ibid. 1967 67 623; Biradicals I. D. Morozova and M. E. Dyatkina Uspekhi Khimii 1968 37 865; Tri- alkyltin Hydrides in Radical Reactions Accounts Chem. Research 1968 1 299; Nitro-aromatic Radical Anions E. Buncel A. R Norris and K. E. Russell Quart. Rev. 1968 22 144; Solvent Effects in Radical Abstraction H. Sakurai and A. Hosomi Yuki Gosei Kagaku Kyokai Shi 1967 25 1108; See also the reviews on stereoselection in organic reactions by S. I. Miller Adv. Phys. Org. Chem. 196%8 p. 185; K. Fukui Kyoto Daigaku Nippon Kagakusem Kenkyusho Koenshu. 1966 23 75. 172 M. J. Perkins series of experiments' with bridgehead carbaldehydes in which the relative stability of the radical R* was inferred from the competition between processes (1) and (2); the order of radical stability CCl, RCO* -RCOCl -co CCl RCO.-R* --% RCl adamantan-1-yl > t-butyl -1-bicyclo[2,2,2]octy1 9 norbornan-1-yl was found. Although it is clear from this that a bridgehead norbornyl radical is particularly unstable the remaining data are inconclusive and assumptions implicit in the interpretation of the competition between paths (1) and (2) may not be valid. More reliable information comes from three independent studies6 of perester (RC0,OBu') decomposition. Peresters with the four R-groups mentioned above were studied. All four appeared to decompose by a concerted two-bond scission RC020But + R* + C02 + *OBut After allowing for differences in inductive effects the rates of decomposition followed the order R = t-butyl > adamantan-1-yl > l-bicycl0[2,2,2]octyl > l-norbornyl(1~0,0~4,0~05,0~004). It was concluded that the preferred geometry of an alkyl radical is planar but that distortion from planarity imposes much less strain than is the case for carbonium ions.In contrast however is the observation that the decomposition of 1,l'-azoadamantane requires an activa- tion energy 20 kcal. greater than does 2,2'-azisobutane ! Hydrogen abstraction from adamantane also yields interesting information,* for whilst the bridgehead position is more prone than is the 2-position towards hydrogen abstraction the bridgehead radical (A') once formed appears to be unusually indiscriminate in subsequent reactions with halogen donors.R* + A'H -+ A'* + RH (3) A'. + RHal+ A'Hal + R* (4) In interpreting these results it was suggested that the transition state for reaction (4)might reasonably have much more adamantanyl-radical character than the transition state for reaction (3). Manifestation of any abnormality in the bridgehead radical due to conformation strain should therefore be more pronounced in the halogen transfer (4). D. E. Applequist and L. E. Kaplan J. Amer. Chem. SOC. 1965 87 2194. J. P. Lorand S. D. Chodroff and R W. Wallace J. Amer. Chem. SOC. 1968 90,5266; R C. Fort and R. E. Franklin ibid.,5267; L. B. Humphrey B. Hodgson and R E. Pincock Canad. J. Chem. 46,3099. ' M. Prochazka 0.Ryba and D.Lim Coll. Czech. Chem. Comm. 1968,33,3387;cf:W. Theilacker and K.-H. Beyer Chem Ber. 1961,94,2968. I. Tabushi J. Hamuro and R. Oda J. Amer. Chem. SOC. 1967 89 7127. Free-radical Reactions Two other interesting studies on radical conformation examine the 9-decalyl radi~al.~ A second stereochemical point which has aroused considerable recent interest is the geometry of vinyl radicals. Radical additions to acetylenes are well documented. lo However when stereoisomeric products are possible these are as a rule both observed. There may be stereoselection in the addition step leading preferentially to one or other vinyl radical but these invert more rapidly than the chain transfer (6)to give olefin. The sides of the equilibrium R'.+ HC=CR2 R' R2 >C* / H R1 R' H \ /R2 )c=c< ,C=C \ H H H R2 R' R2 \/ ,c=c \ (5) may be approached independently using appropriate radical precursors such as the peroxides (lc) and (It).From several studies of this kind" it has become clear that equilibration [equation (5)] is indeed rapid similar product mixtures being obtained from both precursors. The relative proportions of the olefinic products appear to be controlled largely by steric factors in the chain- transfer steps (6).'"In the discussion of these effects Kopchic and Kampmeier" were led to the conclusion that the P-phenylstyryl radical might differ from P. D. Bartlett R E. Pincock J. H. Rolston W. G. Schindel and L. A. Singer J. Amer. Chem. Soc. 1965,87,2590; F.D. Greene and N. N. Lowry J. Org. Chem. 1967,32 875 882. For a recent example see R. M. Kopchik and J. A. Kampmeier J. Amer. Chem. Soc. 1968,w 6733. l1 L. A. Singer and N. P. Kong J. Amer. Chem. Soc. 1966,88,5213,1967,89,5251; J. A. Kampmeier and R.M. Fantazier ihid.. 1966 88 5219 G. D. Sargent and M. W. Browne ibid. 1967. 89 2788 0.Sirnamura. K. Tokumaru and H. Yui Trrrohedron Lcqrm. 1966. 5141. 174 M. J. Perkins other vinyl radicals studied by preferring the linear structure (2);however this conflicts with some recent Japanese work in which considerable (>80%) retention of stereochemistry is observed in the stilbenes derived from decom- positions of both (lc) and (It) (R' = R2 = Ph) in cumene or chloroform at 6OO.l An attempt to generate acetylenic radicals' was unsuccessful but it did reveal a new mode of induced-peroxide decomposition Re + PhC=C*CO,OBu'+ PhC==CR*C02*OBu' + PhC=CR + C02 + *OBu' A similar process was demonstrated for cinnamoyl peroxides.Reactions involving the radical (3) on the other hand occur without rupture of the peroxide bond.14 Me Et Et dMe Et \Me Attempts to observe chemical effects of spin correlation in the geminate pairs of radicals produced in azo-compound decompositions have until recently been unsuccessful. Now Bartlett and his colleagues have discovered that attempts to produce triplet-radical pairs reported in the literature,' had systematically failed. This was because sensitized decompositions had proceeded exclusively by singlet-energy transfer.Triplet-energy transfer leads only to isomerisation about the nitrogen-nitrogen double-bond.16 In the cyclic azo-compound (4)[meso or (i-)I where such isomerisation is not possible triplet-sensitized photodecomposition gives a mixture of almost equal parts of meso- and (+)-cyclobutanes (3.''Thermolysis or direct photolysis on the other hand give cyclobutane in which there is substantial retention of the geometry of the precursor. This is entirely consistent with a much longer life- time for the biradical intermediate in the triplet process. Recent work which shows spin-correlation effects in 1,3-biradicals has also been described.' There is an extensive literature detailing kinetic isotope effects in azo-compound decompositions.Seltzer and Mylonakis have now correlated primary nitrogen-15 effects with data on secondary deuterium effects in the l2 K. Tokumaru in 'Yuriki no Kagaku' p. 123. (see ref. 3). l3 N. Muramoto T. Ochiai 0.Simamura and M. Yoshida Chem. Comm. 1968 717 l4 M. M. Schwartz and J. E. Leffler J. Amer. Chem. SOC. 1968,90 1368. l5 P. D. Bartlett and J. M. McBnde Pure Appl. Chem. 1967 15 89. P. D. Bartlett and P. S. Engel J. Amer. Chem. SOC.,1968,90,2960. l7 P. D. Bartlett and N.A. Porter J. Amer. Chem. SOC.,5317. l8 P. Scheiner J. Amer. Chem. SOC.,1968,90 988. Free-radical Reactions pyrolyses of azo-compounds which decompose by one-bond scission or by symmetrical or unsymmetrical two-bond scission.' Other secondary isotope effects have been reported,20 including the demonstration of an increased cage recombination of radicals from perdeuterioazisobutyronitrile compared with those from the non-deuteriated species.21 Cage effects in general have come in for close scrutiny in particular their variation with pressure and vis~osity.2~-~~ An analysis of the viscosity de- pendence was fitted by Pryor and Smith22 to rate data for the decomposition of acetyl peroxide25 and of p-nitrophenylazotriphenylmethanein a range of solvents.Both reactions had scission of only one bond in the rate-determining step; it was argued that cage effects in reactions exhibiting multiple-bond homolysis in the rate-determining step should not lead to reconstitution of the starting material. This is illustrated schematically single-bond scission R1N=NR2 [R'N=N* + R2] +products concerted two-bond scission R'N=NR2 + [R' + N2 + R2] +products Indeed the dependence of decomposition rate on viscosity could be utilised to distinguish between single- and multiple-bond homolyses.In very viscous solvents much more cage recombination occurs than the Pryor-Smith analysis would predict.26 In recent examples of disproportionation of geminate pairs of radicals in a solvent cage,24. 27 an example has been found in which asym- metry at the radical centre is retained in the disproportionation pr~duct.~' Several groups have sought and occasionally found evidence for neigh- bouring-group effects in homolytic reactions. Of course intramolecular (6) (7) S. Seltzer and S.G. Mylonakis J. Amer. Chem SOC.,1967,89 6586. 2o (a) S. E. Scheppele and S. Seltzer J. Amer. Chem. SOC.,1968 90 358; (b) S. G. Mylonakis and S. Seltzer ibid. 5487; S. Rummel H. Hubner and P. Krumbiegel Z. Chem. 1967,7 351. 21 S. Rummel H. Hubner and P. Krumbiegel Z. Chem. 1967 7 392. 22 W. A. Pryor and K. Smith J. Amer. Chem. SOC.,1967,89 1741. 23 C. Walling and H. P. Waits J. Phys. Chem. 1967 71 2361; 0.Dobis J. M. Pearson and M. Szwarc J. Amer. Chem. SOC.,1968,90,278; K. Chakravorty J. M. Pearson and M. Szwarc ibid. 283. 24 R C. Neuman and J. V. Behar Tetrahedron Letters 1968,3281. 25 Cage effects in acetyl peroxide decomposition have been discussed in detail J. W. Taylor and J. C. Martin J. Amer. Chem SOC.,1967,89,6904; see also J. C. Martin J. W. Taylor and E.H. Drew ibid. 129. " H. Kiefer and T. G. Traylor J. Amer. Chem SOC., 6667. " H. M. Walborsky and C. J. Chen J. Amer. Chem. SOC.,1967,89 5499. 176 M. J. Perkins reactions are well known in radical chemistry as for example in functionalisa- tion of steroidal angular methyl groups in the Barton reaction and related processes.2 However kinetic effects which actually assist initial homolysis are less well documented. Examples in which neighbouring double-bonds appear to facilitate peroxide2' and hypochlorite3* decompositions have appeared ; neighbouring sulphur too can assist peroxide decomp~sition,~ though no evidence for intramolecular stabilisation by sulphur could be found in radical (6).32 Reaction of both syn-and anti-7-bromonorbornene with tributyltin deuteride gives ~nti-7-deuterionorbornene.~ This stereospecificity has led to the postula- tion of a possible nonclassical intermediate (7).However alkyl bridging is not normally encountered in radicals as there is no low-lying orbital available to accommodate the unpaired electron. For this reason 1,2-alkyl shifts are almost unknown in radical chemistry. Vinyl migrations,34- 35 on the other hand like phenyl migrations are well documented. The simplest case the rearrangement of allylcarbinyl itself has been probed by isotopic labelling. Experiments 28 For recent examples see E. Wenkert and B. L. Mylori J. Amer. Chem SOC.,1967,89 174; D. H. R Barton R H. Hesse R. E. O'Brien and M. M. Pechet J. Org. Chem. 33 1562; J. E.Baldwin D. H. R Barton I. Dainis and J. L. C. Pereira J. Chem SOC.(C),1968 2283. 29 R C. Lamb L. P. Spadafino R G. Webb E. B. Smith W. E. McNew and J. G. Pacifici J. Org. Chem. 1966,31 147. 'O J. M. Surzur P. Cozzone and M. P. Bertrand Compt. Rend. 1968,267 C 908. 31 T. H. Fisher and J. C. Martin J. Amer. Chem SOC.,1966,88 3382. 32 J. S. Hyde R Breslow and C. DeBoer J. Amer. Chem. SOC.,1966,88,4763. 33 J. Warkentin and E. Sanford J. Amer. Chem SOC.,1968,90,1667. 34 See for example C. K. Alden D. I. Davies and P. J. Rowley J. Chem. SOC.(C) 1968 705 and preceding papers in this series; D. C. Neckers Tetrahedron Letters 1965 1889; L. H. Slaugh J. Amer. Chem SOC.,1965 87 1522; T. A. Halgren M. E. H. Howden M. E. Medof and J. D. Roberts ibid. 1967 89 3051; S.J. Cristol and R V. Barbour ibid. 1968 90 2832; I. S. Lishanskii A. M. Guliev A. G. Zak 0.S. Fomina and A. S. Khachaturov Doklady. Akad. Nauk SSSR 1966,170,1084. 3s L. K Montgomery J. W. Matt and J. R Webster J. Amer. Chem SOC.,1967 89 923; L. K. Montgomery and J. W. Matt ibid. p. 934 3050. Free-radical React ions 177 involving the radical-chain decarbonylation of the aldehyde (8) confirmed that rearrangement was taking place and the isolation of both cis-and trans-[l-2H]but-l-ene from decarbonylation of (9) implies that the cyclo- propylcarbinyl intermediate (10) is sufficiently long-lived for rotation about the carbon-carbon bond to occur.35 An oxygen analogue of the cyclopropyl- carbinyl to allylcarbinyl rearrangement implicit in the above vinyl migrations has been noted [( 11)+ ( and similar behaviour is found in the decompo- sition of cyclopropyl nitrites [e.g.(13)].37 In these reactions however great instability coupled with the effects of substituents point to rearrangement being concerted with the decomposition. At the other extreme examples have come to light of stabilization of radicals by cyclopropyl substituents which do not ring-open in the course of reaction.38 Me/*\ -Me CH=CH Me CH; (13) (nitroso-dimer) Radical bridging is also possible where the bridging group contains a low-lying d-orbital which can accommodate the unpaired electron as for example in the bromine-bridged structures encountered when bromine atoms add to a double bond.39 Evidence for bridging by sulphur4' and tin4' atoms and a 1,Zshift of a silyl can similarly be rationalised in terms of d-orbital participation.Fragmentation of alkoxy-radicals is well known.43 However the reverse process radical 'addition to a carbonyl group is seldom observed. Examples have been encountered in a further analogue of the allylcarbinyl rearrange- ment,44 in additions to perfluoroalkyl ketones,45 and more recently in the 36 S. K. Pradhan and V. M. Girijaballabhan Tetrahedron Letters 1968 3103. 31 C. H. DePuy H. L. Jones and D. H. Gibson J. Amer. Chem. SOC. 1968,90,5306. J. C. Martin J. E. Schultz and J. W. Timberlake Tetrahedron Letters 1967,4629. 39 See for example P. D. Readio and P. S. Skell J. Org. Chem. 1966 31 753 759; for bromine bridging in a radical elimination see D.M. Singleton and J. K Kochi ibid. 1968 33 1027; J. Amer. Chem SOC.,1968,W 1582; Tetrahedron 1968,24 3503. 40 H. H. Szmant and J. J. Rigau Tetrahedron Letters 1967 3337; N. A. Lebel and A. DeBoer J. Amer. Chem. SOC.,1967,89 2784. *' R H. Fish H. G. Kuivila and I. J. Tyminski J. Amer. Chem. SOC.,1967,89,5861. 42 C. G. Pitt and M. S. Fowler J. Amer. Chem. SOC. 1968,90 1928. 43 A recent discussion is given by K. Maruyama and K. Murakami Bull. Chem. SOC.Japan 1968 41 1401. 44 W. Reusch C. K. Johnson and J. A. Manuer J. Amer. Chem. SOC.,1966,88 2803. 45 E. G. Howard P. B. Sargeant and C. G. Krespan J. Amer. Chem. Soc. 1967 89 1422 178 M. J. Perkins reactions of biacetyl as in the synthesis of acetylcyclohexane outlined below.46 0.There have been numerous investigations of polar effects in radical reactions particularly in hydrogen abstraction^.^^-'^ The selectivity exhibited in reac- tions of aminium cation radicals is particularly dramatic. For example radical chlorination of methyl decanoate with N-chlorodialkylamines in strongly acidic media occurs predominantly (ca. 50%) at C-9. Attack by the aminium cation radical is clearly directed away from the protonated ester function by charge repulsion ; however a similar preference for attack at the penultimate carbon atom found with long-chain hydrocarbons may reflect chain-coiling in the highly polar medium; this would render the internal methylene units relatively inac~essible.~~ The ease of chlorination of substituted toluenes under comparable conditions shows an unexpectedly small substituent de- pendence with p = -1.36 (against a+).48This value for p is comparable with the figure for abstraction by Br*.Hydrogen abstraction from 1-substituted adamantanes by trichloromethyl radicals occurs predominantly (ca. 80 %) from the remainining bridgehead positions. By means of competition studies it was possible to determine variations in bridgehead reactivity as a function of the s~bstituent.~~ In this the first study of polar effects on radical reactions in a rigid aliphatic system correlation with Taft a*-values was excellent (p* = -0.4). The importance of bridged intermediates in radical additions has already been noted. Another topic of current interest in radical-addition reactions is the extension to ring synthesis by intramolecular addition.” 52 In particular Julia’s group has recently succeeded in closing two rings by a combination of radical addition and aromatic substitution [( 141 +(15)]?’ The first cyclisation the addition of the resonance-stabilised cyanoacetate radical to the double- bond is reversible.This allows formation of the thermodynamically preferred six-membered ring. Under conditions of kinetic control cyclopentane forma- tion is commonly preferred.’ Two somewhat different conformational arguments have now been advanced to rationalise this. In the first,54 trans- annular overcrowding is considered responsible. In the second,” a stereo- 46 W. G. Bentrude and K. R Darnall J. Amer. Chem. SOC.1968,90,3588;Chem. Comm. 1968,810. 47 R Bernardi R Galli and F. Minisci J. Chem. SOC. (B) 1968 324. 48 R S. Neale and E. Gross J. Amer. Chem. SOC. 1967,89,6579. 49 P. D. Owens G. J. Gleicher and L. M. Smith J. Amer. Chem. SOC. 1968,90,4122. 50 R. D. Gilliom and J. R Howles Canad. J. Chem. 1968 46 2752; G. J. Gleicher J. Ory.Chem. 1968,33 332; E. S. Huyser and K. L. Johnson ibid. 3952; K. H. Lee Tetrahedron 1968,24,4793. 51 M. Julia and J. C. Chottard Bull. SOC. Chim. France 1968 3691 3700. ’* A recent example is given by J. I. G. Cadogan M. Grunbaum D. H. Hey A. S. H. Ong and J. T. Sharp Chem. and Ind. 1968,422; see also refs. 30 and 55. 53 E.y.B. Capon and C. W. Rees Ann Reports 1964 61 261. 54 M. Julia and M. Maumy see ref. 4. ” D. L. Struble A.L. J. Beckwith and G. E. Gream Tetrahedron Letters 1968? 3701. Free-radical Reactions 179 electronic requirement for approach of the adding radical perpendicularly to one end of the double-bond is assumed; this is shown to be more favourable for cyclopentane formation. The cyclisation of farnesyl acetate by benzoyl peroxide and copper ions,56 possibly typifies a synthetically useful procedure ;however in the opinion of the writer the assignment of a radical mechanism to the cyclisation steps of this reaction is open to question. d;'a/cH2 (PhCO,& OAC f Cu'/Cu" Ph CO "H Intramolecular aromatic substitution by the copper-catalysed decomposition of appropriate diazonium salts has long been considered to involve radical intermediates.However compelling evidence'' has only recently been forthcoming. For example,58 the formation of the dimer (18) from (16) can reasonably be envisaged only as following a radical pathway. Cuprous oxide has proved to be a very much more eficient catalyst for effecting similar cyclisations ;furthermore conditions have been found for diverting the radical either by oxidation to phenol or by hydrogen abstraction from the solvent both in excellent yield." Pyrolysis of the dimer (1 8) gives N-methylphenanthridone almost quan- titatively. Presumably this involves dissociation back to (17) followed by rearrangement to (19) and loss of hydrogen.60 The behaviour of derivatives of (18) clearly demonstrates that an aryl group migrates rather than nitrogen.This rearrangement may have a bearing on the mechanism of intermolecular aromatic substitution by aryl radicals. It is known that competition between pathways (7) and (8) open to the cyclohexadienyl radical (20) is essentially independent of the position of the substituent X.Thus if the yizld of biaryls 56 R Breslow S. S. Olin and J. T. Groves Tetrahedron Letrers 1966 4717; ibid. 1968 1837. " R A.Abramovitch and k Robson J. Chem. SOC.(C),1967 1101. " D.H. Hey C. W. Rees and A. R. Todd J. Chem. SOC.(C) 1518. 59 A. H.Lewin and T. Cohen J. Org. Chem. 1967,32 3844. 6o D.Collington D. H. Hey and C. W.Rees,J. Chem SOC.(C) 1968 1017 1026; D.Collington D. H. Hey C. W. Rees and E. le R. Bradley ibid. 1021. 180 M. J. Perkins 9px 4 \o O5 \/ h r-5 4 -", 0 s \ Free-radical Rwetions 181 Ar (7) X I x + other products (21) is increased at the expense of other products by carrying out the reaction in the presence of an oxidising agent [favouring path (7)] the isomer distribu- tion of the biaryls is unaffected.61 One possible explanation of this (a priori unlikely) result could involve a series of relatively rapid intramolecular aryl shifts [equation (9)].X X X The reaction of benzoyl peroxide with benzene has often been quoted as the typical example of radical substitution. It now seems that it may in fact be somewhat exceptional. In this reaction bimolecular interaction of two cyclohexadienyl radicals [path (8) above] is very important. However this does not occur with other familiar phenylating agents because of the build-up in the reaction system of relatively high concentrations of some oxidising species which efficiently divert the cyclohexadienyl radicals to biaryls or other products with phenylazotriphenylmethane it is the trityl radical,62 with N-nitrosoacetanilide it is the nitroxide (22),63and a nitroxide assumes the same role even with benzoyl peroxide if a nitroaromatic is present.64 Ph*+ N=O PhNO-__L -I I PhNAc PhNAc (22) 61 R T.Morrison J. Cazes N. Samkoff and C. A. Howe J. Amer. Chem. SOC.,1962 84 4152; D. H. Hey M. J. Perkins and G. H. Williams Chem and Ind. 1963 83; D. H. Hey K. S. Y. Liang and M. J. Perkins Tetrahedron Letters 1967 1477; however see H. J. M. Dou G.Vernin and J. Metzger ibid. 1968 953. M. J. Perkins J. Chem. SOC.,1964,5932. 63 G. R Chalfont and M. J. Perkins J. Amer. Chem SOC.,1967,89 3054; A. R Forrester Chem. and Id. 1968 1483; for new data on the rearrangement of nitrosoacylarylamines see C. Ruchardt C. C. Tan and B. Freudenberg Tetrahedron Letters 1968,4019. 64 G. R Chalfont D. H. Hey K. S. Y.Liang and M. J. Perkins Chem Comm. 1967 367. 182 M. J. Perkins The homolysis of benzoyl peroxide in benzene initially produces two benzoyloxy-radicals. It has only recently been fully appreciated that these may add reversibly to the benzene before suffering decarboxylation though an excellent analogy has been in the literature for many years.65 The benzoyl- oxycyclohexadienyl radical can be intercepted by oxygen66 or copper (11) ions67 (to give phenyl benzoate) or by coupling with trityl radicals.68 In the last example,.subsequent elimination of benzoic acid gives tetraphenylmethane (the Wieland tritylation reaction).Ever since Gomberg’s pioneering work nearly 70 years ago the hexaphenyl- ethane structure has been written for the dimer of the trityl radical. This now appears to have been mistaken evidence for the para-coupled alternative (23) having been ~ecured.~’ This type of structure rationalises the steric effects Ar,CH*CHAr (24) I2000 Me displayed by meta-substituents on the dimerisation of hindered diarylmethyl radical^.^' In the same work the normal tetra-arylethane (24) was shown to possess high kinetic stability.However (24) when heated to 200” and then cooled gave an equilibrium mixture of (25)and (26). The field of nitroxide radical chemistry is growing so rapidly as almost to merit a review of its own. Indeed excellent cover.age is available in the volume on stable radical^.^ The relative stability of these radicals coupled with an in- creasing range of reactions whereby they may be produced means that they are particularly well suited for spectroscopic study. They are also however turning up as key intermediates in a growing list of homolytic reactions (e.g. refs. 63 and 64).Nitroxides are readily obtained by radical addition to nitrones” 65 D. B. Denney and P. P. Klemchuk J. Amer. Chem SOC.,1958,80 3289. 66 T. Nakata K. Tokumaru and 0.Simamura Tetrahedron Letters 1967,3303.67 M. E. Kurz P. Kovacic A. K. Bose and I. Kugajevsky J. Amer. Chem Soc. 1968,90 1818; M. E. Kurz and P. Kovacic J. Org. Chem 1968,33 266 1950. 68 T. Suehiro A. Kanoya T. Yamauchi T. Komori and S. I. Igeta Tetrahedron 1968,24 1551. 69 H. Lankamp W. T. Nauta and C. MacLean Tetrahedron Letters 1968 249. ’O W. Theilacker and F. Koch Angew. Chem. Internat. Edn. 1966,5 246. ’’ M. Iwamura and N. Inamoto Bull. Chem SOC. Japan 1967,40 703. Free-radical Reactions 183 and to C-nitroso-compounds.7 The latter reaction has been ingeniously applied to probing y-radiation damage in crystals by allowing the irradiated solid to dissolve in a solution of 2-methy1-2-nitro~opropane.~~ Radical fragments from the crystal were trapped by the nitroso-compound to give a nitroxide the e.s.r spectrum of a solution of which was easily interpreted and the structure of the fragment inferred.Use of the same nitroso-compound has been suggested for mechanistic For example in styrene polymerisation by varying the scavenger concentration it was possible to intercept as nitroxides initiator radical 1:1-adduct of this with styrene and growing polymer radicals. These nitroxides were easily distinguishable by their e.s.r. spectra. Use of nitrones for somewhat similar purposes has also been pr~posed.~’ Another e.s.r. technique holds great promise for direct observation of many reactive radicals in solution high-intensity U.V. irradiation of solutions of t-butyl peroxide in hydrogen-donor solvents at low temperatures has been found to give excellent spectra of solvent-derived radicals.76 The nitronylnitroxides (27),77 and the radicals (28)78 and (29)79provide new examples of particularly stable free-radicals and a revised structure (30) has been demonstrated for Banfield and Kenyon’s radical.80 0 Ph I (30) O‘ There has recently been an extensive literature on reactions involving both radicals and compounds of metals which show variable valence.For example oxidative decarboxylations of carboxylic acids (RC0,H) by lead tetra-acetate are though perhaps not invariably,82 believed to proceed uia radicals (R 0). The reactions ofthis oxidant with a wide range of other compounds have also been e~amined.8~ In many instances of carboxylic acid oxidation 72 E.g.A. Mackor,T. A. J. W. Wajer andT. J. de Boer Tetrahedron 1968,24,1623;G. A. Abakumov and G. k Razuvaev Doklady Akad. Nauk. SSSR 1968,187,95. 73 E. Lagercrantz and S. Forshult Nature 1968,218 1247. 74 G. R Chalfont M. J. Perkins and k Horsfield J. Amer. Chem SOC.,1968,90 7141. ’’ E. G. Janzen and B. J. Blackburn ibid. 5909. 76 P. J. Krusic and J. K. Kochl J. Amer. Chem. Sac. 1968,90 7155; J. K. Kochi and P. J. Krusic ibid. p. 7157; J. Q. Adams ibid. p. 5363. 77 J. H. Osiecki and E. F. Ullman J. Amer. Chem. SOC.,1968,90,1078; D. G. B. Boocock R. Darcy and E. F. Ullman ibid. p. 5945; D. G. B. Boocock and E. F. Ullman ibid. p. 6873; k T. Balaban P. J. Halls and A. R Katritzky Chem and Ind. 1968,651;see also L. B. Volodarsky G.A. Kutikova R Z Sagdeev and Y.N. Molin Tetrahedron Letters 1968 1065. ” H.M. Blatter and H. Lukaszewski Tetrahedron Letters 1968 2701. 79 A. T. Balaban P. T. Frangopol M. Frangopol and N. Negoita Tetrahedron 1967,23,4661. R. Foster J. Iball and R. Nash Chem. Comrn. 1968 1414. J. K. Kochi J. Amer. Chem. SOC.,1965,87 3609; J. K. Kochi J. D. Bacha and T. W. Bethea ibid. 1967,89 6538; D. I. Davies and C. Waring J. Chem. SOC.(C),1968 1865. 82 D. I. Davies and C. Waring J. Chem. SOC.(C),1968 2332 2337. 184 M. J. Perkins the intermediate radical may be intercepted by copper@) in a process of oxida- tive eliminati~n.~~ Thus cyclobutanecarboxylic acid is efficiently oxidised by lead tetra-acetate and copper(r1) ions in acetic acid to give cyclobutene. The elimination appears to involve concerted collapse of a cyclobutylcopper species.Similar behaviour is found for the Cu" oxidation of cyclobutyl radicals formed in the Cu'-induced decomposition of bis(cyclobutylformyl)peroxide? Oxidative bis-decarboxylation of a vicinal dicarboxylic acid to an olefin commonly effected by lead tetra-acetate may often be carried out in superior yield by anodic oxidation.86 In this brief survey an attempt has been made to highlight some of the areas of recent or current interest in free-radical chemistry. In such a short space many topics have inevitably not been touched upon. One of these of immense commercial significance is autoxidation. This is mentioned now because a feature evident in more recent radical chemistry is the increasing proportion of work in which absolute rate constants for radical reactions have been esti- mated:' and this exemplified in many studies related to autoxidation notably by Howard and Ingold and their colleagues.88 One final point on autoxidation concerns chain-termination.It has been known for some time that chain termination between pairs of primary or secondary peroxy-radicals is much faster than with tertiary ones. A mechanism proposed by Russell8' to accommodate this involving the electrocyclic process indicated should generate singlet oxygen. That this indeed occurs has been demonstrated by a successful trapping experimentg' 0,(Singlet) 2R2CHO0. R2Co HOCHR CHR 83 E. I. Heiba R M. Dessau and W. J. Koehl J. Amer. Chem SOC.,1968,90 1028 2706; W.H. Starnes ibid. p. 1807; R 0.C. Norman and C. B. Thomas J. Chem SOC.(B) 1967 771; 1968 994; B. C. Gilbert and R 0.C. Norman ibid. 1968 123; R 0.C. Norman and R A. Watson ibid. p. 184; W. H. Starnes J. Org. Chem. 1968 33 2767; G. Just and K. Dahl Tetrahedron 1968 24 5251 ;J. Lhomme and G. Ourisson ibid. pp. 3167 3177 3201; M. L. Mihailovic Z Cekovic V.Andrejevic, R Matic and D. Jeremy ibid. p. 4947; J. B. Aylward and R 0.C. Norman J. Chem. SOC.(C) 1968 2399. 84 J. D. Bacha and J. K. Kochi Tetrahedron 1968,24,2215;J. Org. Chem. 1968,33,2746. 85 J. K. Kochi and A. Bemis J. Amer. Chem SOC. 1968,90,4038; see also J. K. Kochi A. Bemis and C. J. Jenkins ibid. p. 4616. 86 P. Radlick R Klem S. Spurlock J. J. Sims E. E. van Tamelen and T. Whitesides Tetrahedron Letters 1968 5117; H.H. Westberg and H. J. Dauben ibid. p. 5123. 87 A useful compendium of estimated absolute rate constants was given by D. F. DeTar J. Amer. Chem. SOC. 1967,89,4058. ** See for example J. A. Howard and K. U. Ingold Cad. J. Chem. 1967,45 785 793; 1968,46 2655 2661; J. A. Howard K U. Ingold and M. Symonds ibid. 1968,46 1017. 89 G. A. Russell J. Amer. Chem. SOC.,1957 79 3871. Free-radical Reactions Other topics not reviewed here include the chemistry of the monovalent carbon species (:&O,Et) generated recently,” y-radiolysis studies radical ions electron-transfer processes solvent .effects and many aspects of the appli- cation of magnetic resonance techniques. It is hoped that emphasis on some of these topics may be possible in future reports.J. k Howard and K. U. Ingold J. Amer. Chem SOC. 1968,90,1056,1058. 91 T. DoMinh H. E. Gunning and 0.P. Strausz,J. Amer. Chem SOC.,1967,89,6785;0.P.Straw T. DoMihn and J. Font ibid. 1968,90 1930.

ISSN:0069-3030    

DOI:10.1039/OC9686500171

出版商:RSC    

年代:1968

数据来源: RSC