ORGANIC CHEMISTRY1. INTRODUCTIONBy W. I). Ollis(Department of Chemistry, Ufiiversity of She$Leld)and J. H . Ridd(Department of Chemistry, University College London, London W.C. 1)No major changes have been made in the form of this year’s Report, butthe size has been considerably increased and this has permitted a furthersub-division of certain topics. Thus, the section on Physical Methods ofStructure Determination is now discussed under the headings (a) NuclearMagnetic Resonance, (b) Electron Spin Resonance, ( c ) Optical RotatoryDispersion and Circular Dichroism, and (d) Mass Spectrometry. In general,the content of these and other sections of the Report will be apparent fromthe titles, but some comments on the division of the material may be helpful.The section on Reaction Mechanisms includes quantitative studies of sub-atituent effects and material bearing on the detailed structure of inter-mediates or transition states.Many papers dealing with more qualitativeaspects of reaction mechanism are discussed in the other sections. Aslast year, the section on Organometallic Compounds deals mainly withorganic derivatives of the non-transition metals with carbon-metal bonds ;the organic chemistry of ligands attached to transition metals is describedin the Inorganic Chemistry Report.The wide range of the Organic Chemistry Report and the large amountof material included in it always make it difficult to pick out the moreimportant advances of the year, but the following survey indicates somerecent developments of novelty or general interest.Important developments in the computerised interpretation of massspectral information have been reported and further progress has beenmade in the application of nuclear magnetic resonance spectroscopy tostereochemical problems and the study of conformational equilibria.Thedifferences in the nuclear magnetic resonance spectra of enantiomers inchiral solvents can provide a criterion of optical purity. Abnormally largelong-range coupling constants in certain bicyclic and tricyclic rings havebeen related to particular stereochemical situations.A considerable amount of work has already appeared which has beenstimulated by the theory put forward last year by Woodward and Hoffmannto account for the facility and stereochemistry of certain concerted cyclo-additions, eliminations, and rearrangements.The new work, in particularthat on fragmentation reactions in cyclic systems, accords with the theoryand extends the range of application. There is much interest in photo-chemical cycloadditions involving reactions which, on considerations oforbital symmetry, are thermally forbidden. Many other references reflectingthe current interest in photochemical reactions will be found throughou$the Report, the rationalisation of the photochemical reactions of benzen240 ORGANIC CHEMISTRYby Bryce-Smith and Longuet-Higgins being particularly noteworthy.Their approach, and that of Woodward and Hoffmann referred to above,relies on symmetry correlations between all of the relevant molecular orbitalsin the reactants and products.The success of such arguments suggeststhat the chemical intuition of the future organic chemist will have to begrounded in a sound appreciation of orbital symmetry.Other recent work in physical organic chemistry has served to definefurther the significance of such mechanistic criteria as acidity functionsand isotope effects. The substituent effects on the 19F chemical shifts inbiphenyls and terphenyls suggest that the earlier interpretation of suchsubstituent effects in benzene derivatives needs to be reconsidered. Someelegant studies are now available concerning the saturation of substituenteffects in the stabilisation of carbonium ions and carbanions.The preparation and properties of the annulenes continue to provideresults of great interest.The evidence for paramagnetic ring currentsin the non-aromatic annulenes with 4n n-electrons accords with the quantummechanical treatment of these systems. Some bridged annulenes have nowbeen prepared. Other novel compounds prepared during the year includeorganometallic compounds with bonds between dissimilar metals, as exempli-fied by novel structures associated with germanium-lead and tin-zincbonds.Interesting investigations on tropilidene rearrangements, the photo-chemical rearrangements of diphenylcyclohexadienones, and cyclopropyl-ally1 transformations of carbanions and cations have been reported. Thisyear it has been found necessary to provide a separate section on terpenoidsand steroids and, in addition to the many interesting examples of structuredetermination which are reviewed, the isolation, proof of structure, andsynthesis of the insect moulting hormones should be separately mentioned.The detailed understanding of the mechanism of the cyclisation of squalenein its biosynthetic transformation into lanosterol and cholesterol is extendedby the demonstration that squalene-l,2-epoxide functions as a genuineintermediate; on this basis the cyclisation of several terminal epoxidesmay be regarded as examples of biogenetic type syntheses.Activities associated with the chemistry of heterocyclic compoundscover a tremendous range, but undoubtedly the outstanding achievementof the year in this area was the total synthesis of cephalosporin-C. Consider-able interest in the study of the photochemical rearrangements of hetero-cyclic compounds is now beginning to develop.Novel observations includethe elucidation of the constitution of a marine antibiotic containing over70% bromine and the thermal stability of thiiren-1,l-dioxides. The decisiontaken last year to include a discussion of the chemistry of the monosaccharidesin the heterocyclic compounds section has been continued, and it may benoted that there is still considerable interest in the effect of polar substituentsupon the conformational equilibria of cyclic carbohydrate derivatives. Itis, however, questionable whether special terms are still required to referto this effect (the anomeric effect) and to describe carbohydrate conforma-tions since these studies belong to the continuing general study of theconformational behaviour of cyclic compounds.The reactions of carboOLLIS AND RIDD: INTRODUCTION 241hydrates have provided a large number of interesting examples of neigh-bouring-group participation and this year the isolation of several stable1,2-dioxolenium hexachloroantimonates has been described. This is ofinterest in relation to earlier postulates that these cations were intermediatesin many reactions of carbohydrates.X-Ray crystallographic methods for structure determination have beenextensively used this year in the alkaloid field, which is perhaps not toosurprising in view of the remarkable complexity of many natural productsof this type that have been recently isolated. The discovery that severalnew alkaloids appear to be effective against leukaemia and other forms ofcancer is bound to provide a further powerful stimulus to alkaloid chemistry.Undoubtedly the most striking advance in technique in peptide chemistrywhich has taken place recently is the discovery of solid-phase synthesis,and the application of this technique and the search for new coupling re-actions has continued.The syntheses of the hormone secretin and the beevenom substances mellitin and neben-mellitin are particularly noteworthyand full details of the outstanding total synthesis of the adrenocortico-trophic hormone announced two years ago have now been published.The chemical synthesis of the sixty-four isomeric trinucleoside di-phosphates has been achieved by Khorana, and he has used polynucleotidesof known sequence as messengers for protein synthesis, thus providingadditional confirmation of the genetic code.This code has also been con-firmed using proflavin mutants in a remarkably elegant and satisfyingmanner. Progress with the determination of the primary structure ofpolynucleotides is exemplified by the announcement of complete nucleotideaequences for several s-RNAs. One wonders how long it will be beforethese chemical studies are complemented by X-ray crystallographicalresults.Last year a new section dealing with biosynthesis was created andnew results continue to justify this. Progress continued with the studyof the biosynthesis of polyketides and polyacetylenes, and it has beenshown that C-3 oxidation can occur after cyclisation to the triterpenoidskeleton has taken place.The suggestion that the C1, or C, fragments ofa number of indole alkaloids were derived from two molecules of mevalonicacid has been confirmed and knowledge regarding these biosyntheses hasbeen extended by the incorporation of the labelled monoterpenoids geranioland loganin, during several alkaloid biosyntheses. The elucidation byCornforth and Popjhk of the stereochemical detail of the biosynthesis ofsqualene from mevalonate is clearly an outstanding achievement. Thedetails of this investigation have been published recently and the resultsprovide a beautiful example of the stereospecificity of biosynthetic processesinvolving prochiral centres2.PHYSICAL METHODS OF STRUCTURE DETERMINATIONPart (i) Nuclear Magnetic Resonance SpectroscopyBy J. Feeney( Variam Research Laboratory, Walton-on- Thames, Surrey)0 R G AN I c chemists involved in problems of molecular structure are nowfully exploiting the technique of nuclear magnetic resonance spectroscopy(n.m.r.). It has been estimated that one in six of all papers in chemistryjournals published in 1966, contains some reference to the subject. In theliterature of the past year, there is evidence that the amount of fundament-ally new n.m.r. data is not increasing dramatically. However, use of thesophisticated application of n.m.r. to molecular structure determination isbecoming even more widespread, particularly in the detailed study of intra-molecular dynamic processes.In this Report, no attempt has been made topresent a comprehensive survey of the numerous n.m.r. publications.Several textbooks and review articles on the subject have appeared in thecurrent year.lChemical-shifts.-Attempts to calculate chemical shifts in terms ofspecific models (such as those based on anisotropic effects, or electric-fieldeffects) continue to be made. Whilst recognising the shortcomings of anyapproach of this type, it is clear that the effects on shielding of electric fieldshave been underestimated in the past.Yonemoto 2 has described a perturbation method to calculate the effectsof electric interactions on proton shielding. In another publication thecontribution to lH, l9F, and 13C, chemical shifts from intramolecular electricfields has been e~aluated.~ Where the examined nucleus is in close spatialproximity to polarisable groups such effects are important.The contribu-tion t o the shielding is given byBelectric = --AAEz - B(AE2 + A<B2>)where A and B are constants, E is the electric field produced a t the nucleusby a point dipole at the centre of any polar bond, Ez is electric field com-1 R. H. Bible, “Guide to the N.M.R. Empirical Method,” Plenum Press, New York,1966; J. W. Emsley, J. F:mey, and L. H. Sutcliffe, “High Resolution Nuclear MagneticResonance Spectroscopy, vols. I and 11, Pergamon Press, London, 1966; “Progress inNuclear Magnetic Resonance Spectroscopy,” vol. I, ed.J. W. Emsley, J. Feeney, andL. H. Sutcliffe, Pergamon Press, London, 1966; I. V. Aleksandrov, “The Theory ofNuclear Magnetic Resonance,” Academic Press, London, 1966; D. Chapman and P. D.Magnus, “Introduction to Practical High Resolution Nuclear Magnetic ResonanceSpectroscopy,” Academic Press, London, 1966; “N.M.R. for Organic Chemists,” ed.D. W. Mathieson, Academic Press, London, 1967; Koji Nakanishi, Lois Durham, andM. C. Woods, “A Guide to the Interpretation of N.M.R. Spectra,” Holden-Day Inc,New York, 1966; “Formula Index to N.M.R. Literature Data,” vols I and 11, ed. M. G.Howell, A. S. Kende, and J. S. Webb, Plenum Press, New York, 1966. Sadtler ResearchLaboratories N.M.R. Spectra Catalogue, Philadelphia; G. Mavel, ‘‘Theories Molkculariesde la Resonance Magnbtique Nuclhaire, Applications a 1% Chhie Structurale,” ed. Dunod,Paris, 1966; “Molecular Relaxation Processes,” Academic Press, London, 1966; R.C.Cookson, T. A. Crabb, J. J. Frankel, and J. Hudie, Tetrahedron, 1966, 7, 355.2 T. Yonemoto, Canad. J. Chem., 1966, 44, 223.3 5. Feeney, L. H. Sutcliffe, and S. M. Walker, Mol. P h p . , 1966, 11, 117FEENEY : NUCLEAR MAONETIC RESONANCE SPECTROSCOPY 243ponent along bond direction, < E2 > is the time averaged square of theelectric fields produced at the nucleus by fluctuating dipoles. This latterterm often dominates the effect.3, 4 Hruska and co-workers have pointedout a linear correlation between lH and 191F shifts in conjugated hydrocarbonsand an empirical parameter Q given byQ = P/Ir3where P is polarisability of C-X bond, I is first ionisation potential of X andr is the G-X bond length.A review of diamagnetic anisotropy effects has been written,g and papersdealing with such effects for C=O,' GC, G-H, and C=C8 bonds haveappeared.The chemical shifts for a, proton in a steroid on going from anunsubstituted to a substituted molecule can be predicted from the algebraicsum of the screening constants for all the bonds displaced, together with allthe bonds introduced.* Abraham and Thomas have considered criticallythe determination of ring currents in aromatic molecules from observedproton chemical-shifts. For such effects, Musher lo has pointed out the factthat the shielding contributions in aromatic systems, which are normallyattributed to n-electron ring currents, can be equally well represented ascoming from the sum of contributions from localised n- and a-electrons.Theoretical studies on the observed chemical shifts in conjugated mono-cyclic polyenes have been carried out by Pople and Untch.ll From con-siderations of the ring currents it is predicted that both paramagnetic (for4n z-electron systems) and diamagnetic (for 4n + 2 systems) shieldingcontributions are possible, By applying the results of the calculations t oan extensive collect'ion of data for annulenes and dehydroannulenes, theydemonstrated the validity of their approach.For molecules with 4n n-elec-tron systems, protons outside the ring are displaced to high field and thoseinside to low field, which is opposite to the beliaviour found in normalaromatic rings.The n.m.r. spectrum of a typical 4n n-electron system, suchas bisdehydro[l6]annulene provides evidence for such paramagnetic ringcurrents.13C chemical shifts have been calculated using a SCB-MO calculation.12Many interesting and useful empirical correlations involving chemicalshifts have been pointed out. For example, linear relationships are foundbetween proton shifts and calculated n-electron densities in nitrogen hetero-c y c l i c ~ , ~ ~ and between proton shifts and Hammett o-constants in aromaticcornpounds.l4 Katrit'zky and co-workers fbd that the change in chemicalG. L. Caldow, Mol. Phys., 1966, 11, 71.F. Hruska, H. M. Hutton, and T.Schaefer, Cunad. J . Chem., 1965, 43, 2392.J.-L. Pierre, An%. Chim., 1966, 1, 187.D. L. Eooper and R. Kaiser, Cunad. J . Chern., 1965, 43, 2363.J. W. Apsimon, W. G. Craig, P. V. Demarco, D. W. Mathieson, L. Saunders, andR J. Abraham and W. A. Thomas, J . Chem. SOC. ( B ) , 1966, 127.lo J. I. Musher, J . Chem. Phys., 1965, 43, 4081.l1 J. A. Pople and K. G. Untch, J . Amer. Chem. Soc., 1966, 88, 4811.l2 S. Forsen and T. Alm, Atta Chem. Scand., 1965, 19, 2027.l3 B. M. Lynch and H. J. M. Don, Tetrahedron Letters, 1966, 23, 2627.l4 S. H. Marcus, W. F. Reynolds, and S. T. Miller, J. Org. Chem., 1966, 31, 1872;W. B. Whalley, Chem. Comm.., 1966, 359.J. G . Traynham and G. A. Knesel, ibid., p. 3350244 ORGANIC CHEMISTRYshift AS of an aromatic ring proton at position a by a substituent X at anortho position b is related linearly to the orth-coupling constant Ja,a betweenthe protons in these positions in the corresponding unsubstituted compound.15Pascual and co-workers l6 have provided a very useful rule for estimatingthe chemical shifts of vinylic protons.Useful chemical-shift data hasappeared for formyl protons in aliphatic l7 (RC€€,*CHO, dCHO = 9.71 & 0.02p.p.m.; R,C-CHO, 6 ~ ~ 0 = 9.36 5 0.03 p.p.m.) and aromatic aldehydes,l*cyclohexanols,ls the OH- ion 2o (6 = 2.12 p.p.m.), thioaldehydes 21 (6 = 10.69p.p.m.) and methylene protons adjacent to C-C multiple bonds.,, Evaluationof the effects on ring proton shielding of methyl- 23 and nitro-substitution 24of aromatic rings has been made.It is well-known that protons attachedto the a-carbon atom of the alcohol moiety of esters are deshielded appreci-ably compared with the same protons in free alcohols (this is referred toas the acylation shift). Culvenor 25 has used these shifts in the conformationalanalysis of esters and lists those for several alcohols.By comparing the n.m.r. shifts of an absorption in the presence of adouble bond with that in the saturated analogue, the proton can sometimesbe assigned if it is spatially near t o the double bond.26 This approach hasbeen used to assign configurations in four membered rings of some tricyclo-[4,2,2,0]-7-decenes.13C shifts in benzaldehydes 27 and methylbenzenes 2* have been reported;when two aromatic methyl groups are ortho to each other, the methyl 1SCshifts are influenced by steric interactions and the methyl conformationscan be characterised by the observed chemical shifts.30 benzenes,31and cyclohexanes.In 1 -substituted 2-chloro- 1,1,2-trifluoro-ethanes,CF,QCFHCl, the geminal F-I? coupling constant shows a linear relationshipwith the reciprocal of the electronegativity of Q.29Coupling Constants.- In 1965, Pople and co-workers 33 successfullyexplained observed trends in geminal H-H and other coupling constantsusing a MO approach. They have shown that for geminal H-C-H couplingconstants the coupling becomes more positive as the carbon s-character16 A. R. Katritzky, B. Ternai, and G. J. T. Tiddy, Tetrahedron Letters, 1966, 16,1713.18 C. PascuaI, J. Meier, and W.Simon, Helv. Chim. Acta, 1966, 49, 164.1 7 R. E. Klinck and J. B. Stothers, Canad. J . Chem., 1966, 44, 45.18 M. Anteunis and Y. Rommelaere, Bull. SOC. chim. belges., 1966, 75, 89.l9 E. L. Eliel and F. J. Biros, J . Amer. Chem. SOC., 1966, 88, 3334.2 0 G. M. Sheldrick, Chem. Comm., 1966, 673.21 S. McKenzie and D. H. Reid, Chem. Comm., 1966, 401.22 M. van. Gorkom and G. E. Hall, Spectrochim. Acta, 1966, 22, 990.%3 G. S. Reddy, 2. Naturforsch., 1966, 21a, 609.24 R. W. Franck and M. A. Williamson, J . Org. Chem., 1966, 31, 2420.25 C. C. J. Culvenor, Tetrahedron Letters, 1966,10, 1091.26 J. P. Snyder and D. G. Farum, J . Org. Chem., 1966,31, 1699.27 A. Mathias, Tetrahedron, 1966, 22, 217.28 W. R. Woolfenden and D. M. Grant, J. Amer.Chem. SOC., 1966, 88, 1496.29 J. Dyer and J. Lee, Trans. Faraday Soc., 1966, 62, 257.30 J. Jullien and H. Stahl-Lariviere, Bull. SOC. chim. France, 1966, 1, 420.3 1 J. Homer and L. F. Thomas, J. Ch,em. SOC., ( B ) 1966, 141.92 J. A. Martin, M. Chauvin, and J. Levisalles, Tetrahedron Letters, 1966, 25, 2879.83 J. A. Pople and D. P. Santry, MoZ. Phys., 1964, 8, 1; J. A. Pople and A. A.19F chemical shifts have been measured forBothner-By, J . Chern. Phys., 1965, 42, 1339FEENEY : NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY 245increases. In addition, if electrons are withdrawn from the carbon orbitalsby inductive effects the positive contribution to the coupling increases whilehyperconjugative withdrawal leads to negative contributions. Using thisapproach, van Duijneveldt and co-workers 34 have calculated couplingconstants between directly bonded 13GH and 13C-13C nuclei in simplemolecules (alkanes, alkenes, alkynes, benzene, and pyridine) ; other workershave calculated 13C-H values in vinyl halide~.~5 Several 13C-G-H couplingconstants have also been rationalised in this way 36 and Jones and Murrell 37have used a MO approach to calculate the ring proton coupling constants inp - benzoquinone.A one-parameter alternant molecular orbital method has been successfdin predicting negative signs for geminal H-H coupling constants and couplingconstants of either sign for the vicinal coupling con~tants,~8 assuming theFermi Contact term to be the dominant contribution.Similarly, results insemiquantitative agreement with observed values for direct 13GH couplingconstants have been cal~ulated.~~ Sackmann *O has used a Dirac vectormodel to calculate such coupling constants in hydrocarbons.A relationship between dihedral angle 4 and vicinal H-H coupling con-stants has been calculated using perturbation theory.41where A = -0-2033, B = -0.6275 and C = 8-4869Anteunis 42 has considered the effects of non-bonding orbitals from oxygenand nitrogen atoms on geminal and vicinal proton coupling constants.An example of where the Karplusrelationship cannot be used to discriminate between a cis-transdiastereoiso-meric pair, is provided by the 3-methylproline derivatives 43 (1) and (2):the J2,3 vicinal H-H coupling constants in the two isomers are almostidentical (7.8 c./sec.).Jn,Eod~ = A + B COB + C coa s+Vicinal H-H coupling constants..MeIn furanose compounds where there is a flexible ring system, JH(l)H(B) valuesrange from 3*5--8.0 c./sec. for cis- and 0-0-8*0 c./sec. for trans-hydrogens,thus allowing diagnostic use of the coupling constants only when J < 1 c./sec.(trans H,H,). Cushley and co-workers 44 have reported a method for assigning3 4 F. B. van Duijneveldt, V. M. S. Gil, and J. N. Murrell, Theor. Chim. Ada, 1965,4, 85.36 V. S . Watts and J. H. Coldstein, Theor. Chim. Acta, 1966, 4, 265.36 K. A. McLauchlan and T. Schaefer, Canud. J. Chem., 1966,44, 321.37 G. T. Jones and J. N. Murrell, J . Chem. Xoc. (A), 1966, 1421.58 M. Barfield, J . Chem. Phys., 1966, 44, 1836.39 R.C. Fahey, G. C. Graham, and R. L. Piccioni, J . Amer. Chem. Soc., 1966,88,193.40 E. Sackman, Ber. Bunsengesellschaft, Phys. Chem., 1965, 69, 919.41 P. Chandra and P. T . Narasimhan, Mol. Phys., 1966, 11, 189.42 M. Anteunis, Bull. SOC. chim. belges, 1966, 75, 413.43 J. Kollonitsch, A. N. Scott, and G. A. Doldouras, J . Amer. Chem. SOC., 1966, 88,44 R. J. Cushley, K. A. Watanabe, and J. J. Fox, Chern. Comm., 1966, 598.3624246 ORGANIC CHEMISTRYanomeric configurations in pentofuranosyl pyrimidine nucleosides whichrequires only one anomer and which is based on removal of anisotropiceffects on hydrogenating double bonds. However, it is possible to dis-tinguish between isomeric 2’- and 3’-ribonucleoside derivatives of type (3)and because JIp, 2’ is less in (3) than in (4) and H(1’) is a t lower field in(3) than in (4).R ’0 - C HZ4 ’HO OR (3) RO OH (4)Coupling constants in the a-(5) and ,946) isomers of 4-benzoyloxyflavanshave been reported;46 the values can be used to determine configuratiomof related molecules.a-isomer Ja,sc = 3.0, Ja,sa = 11.9, J3e,4 = 3.0, J3aJ4 = 3.0, J3e,30 = 13.0 c./aec./I-isomer JaJSc = 2.2, J2,3e = 11.5, J3+ = 6.2, J3a,4 = 10-2, J3e,3a = 13-3 C./WCIn a large series of 4,6-O-benzylidene-aldohexopyranosides,47 the equatorialHL-equatorial H, couplings are 0-6-1.7 c./sec., whereas equatorial HI-axialH, couplings are 3-3-34 c./sec.In -C,HX-C2H < fragments, v i c h l33-H coupling constants decrease as the electronegativity of X increases, afact which has been explained in terms of rehybridisation and inductiveeffects.Such effects would be expected to decrease in a monotonic fashion asone increases the length of the fragment XC1H-C,H-C,H-C4H. However,Cohen and Schaefer 48 have correlated J2,5v*c and J3,4uic from many com-pounds with electronegativity and find that J2.3Dfc values increase withelectronegativity and J3.4u*c values decrease. Although the changes aresmall, it does suggest that hyperconjugative effects on J2,3u2c coupling mightbe important. In monosubstituted aromatic compounds (7), the vicinalcoupling Jl,a increases with electronegativity of the substituent X, whichis also inconsistent with current ideas explaining Pic in CH-CHX fragmentsin terms of rehybridisation and inductive effects which would have predictedthe opposite behavi0ur.4~Tetrahedron, 1966, 22, 705.Lillya, Tetrahedron, 1966, 22, 621.I6 H.P. M. Fromageot, B. E. Griffin, C. B. Reese, J. E. Sulston, and D. R. Trentham,‘ 8 B. J. Bolger, A. w e , K. 0. Marathe, E. M. Philbin, M. A. Vickars, and C. P.B. Coxon, Tetrahedron, 1965,21, 3481.A. D. Cohen and T. Schaefer, MoZ. Phys., 1966, 10, 209.S. Castellano and C. Sun, J . Amer. Chem. SOC., 1966, 88, 4741FEENEY : NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY 247Coupling constants involving l 3 ~ r b o n . Directly bonded 13CH couplingconstants in methyl derivatives have been linearly correlated with G-Hstretching frequencies 5O and with electronegativity of substituents for eachatomic period.51 13C-H coupling constants should become increasingly moreimportant in structural studies as the amount of available data increases(see ref.52 on cyclic and heterocyclic molecules).Observation of J ( l3C-C-C-H) values at various temperatures could wellprovide an additional method for following rotational isomerism; in pro-pionaldehyde-3-13C the trans J ( 13C-C-C-H) value (3.5 c./sec.) is larger thanthe gauche value (0.2 c . / s ~ c . ) . ~ ~Coupling constants involving Fluorine. JmetaFF and Jpa7$F values in fluoro-benzenes have not been easily distinguished in the past because of the over-lap of the possible range of their values. However, sufficient JmetzF valueshave now been measured to indicate that these couplings can be predictedon the basis of additive substituent contributions.54 Extensive lQF couplingconstants data have been published for perfluorovinyl derivatives 55 (JgemFFdepends on the conjugating ability of X) and for acyclic and cyclic fluoro-rtlkene~.~~Long-range coupling constants. With the more widespread use of n.m.r.spectrometers of high resolution and stability, long-range coupling constantsbetween nuclei separated by four or more bonds are being frequently re-ported. These coupling constants can provide an extra parameter for usein structural determinations since the couplings are usually strongly stereo-specific. To measure coupling constants of less than 0.2 c./sec., it isnecessary to de-gas the samples rigorously and to sweep the spectrum slowly(4.1 c./sec.-2). In unsaturated systems long-range coupling is promotedby c-n interactions, while in both saturated and unsaturated systems thelargest couplings are invariably observed when the bonds between the inter-acting nuclei have a zig-zag configuration (sometimes referred to as a Wconfiguration).Thus a large long-range coupling constant (J = 2.3 c./sec.)over five single bonds is observed in the proton spectrum of endo-tricyclo-[3,2,1,0,29 4]oct-6-ene (8).T. L. Brown and J. C. Puclrett, J . Chem. Phya., 1966, 44, 2238.61 A. W. Douglas, J . Chem. Phys., 1966, 45, 3465.P. Laszlo, Bull. SOC. chim. France, 1966, 2, 558; E. J. Vincent and J. Metzger,ibid., p. 491.5s G. J. Karabatsos, C. E. Orzech, and E. N. Hsi, J . Amer. Chem. Soc., 1966,88,1817.54 R. J. Abraham, D.B. MacDonald, and E. S. Pepper, Chem. Cornm., 1966, 642;A. Peake and L. F. Thomas, ibid., p. 529.6 5 C. G. Moreland and W. S. Brey, J . Chem. Phys,, 1966, 45, 803.66 M. G. Barlow, Chem. Comm., 1966,703; J. Reuben and A. Demiel, J . Chem. Phys.,1966, 44, 2216; A. B. Clayton, R. Staphens, and J. C. Tatlow, J . Chem. Soc., 1965,7370248 ORGANIC CHEMISTRYThis large value is attributed to the double zig-zag path of o-bonds betweenthe interacting protons.57 A collection of large long-range coupling con-stants extracted from the literature was similarly explained. Long-rangecoupling across the oxygen atoms of lY3-dioxans has also been reported,589 59e.g., for 4-phenyl-1,3-dioxan (9) we obtain 59 Jze, eS = 1.5, J2e, 6e = 0.9,The largest values are again observed for nuclei connected by zig-zag bondpaths (2e, 6e and Ze, 5e). Long-range coupling features in the protonspectra of bicyclo[3,2,0]-hepta-3,6-dienes (10).60Long-range coupling constants have been reported in 1,4-benzo- quinones,61bicyclo - [ 2,2,1]- heptan-4,5-diones, 13 napht hoquinolines, benzaldehydes,64thionaphthenes (J2.6 = 0.5 c ./ s ~ c . ) , ~ ~ and cyclobutanes.66 It is possibleto use long-range coupling constants as an aid to spectral assignment,67, 6% 69by assuming that four-bond long-range couplings are largest when the inter-acting nuclei have a zig-zag W configuration.Line widths of angular methyl groups in a large number of cis- and truns-decalins and steroids are always larger in the truns-fused isomer, because oflong-range four-bond coupling between the methyl and ring protons whichwill be larger in the trans-fused compounds because more of the interactingnuclei can adopt the favourable coplanar W configuration.6s Calculationsof long-range coupling constants have been made by E'rischleder and co-w0rkers.7~ Long range five-bond H-F coupling in alkyl fluorobenzeneshave led Myhre and co-workers 71 to postulate a " through-space " mech-anism for H-F long-range coupling.In 3-bromo-2,4,6-tri-isopropylfluorobenzene, a value of JHp5 = 1-8 c./sec.is observed for coupling between the ring fluorine and the methyl protonsof the adjacent isopropyl group.Novel Applications.-By using 13C labelled acetate in the biosynthesisof griseofulvin, it is possible to observe, from the 13CH satellites in theproton spectrum of the labelled compound, where the 13C atoms are located:'%the 1% labelling procedure would require degrading the labelled compoundto identify the specifically labelled carbon atoms by their radioactivity.Enantiomers are in different average environments when they are dissolvedJ2c,6a = 0.5, J6e,4a 0.5, J6e,2a = 0.4, J60,4a == 0.4, J6.2, = 0.3 C./SeC.5 7 K.Tori and M. Ohtsuru, Chem. Comm., 1966, 886.68 J. Delmau and J. Duplan, Tetrahedron Letters, 1966, 6, 559.6 9 K. C. Ramey and J. Messick, Tetrahedron Letters, 1965, 49, 4423.6 1 R. K. Norria and S. Sternhell, Austral. J . Chem., 1966, 19, 617.8 8 G. Chalier, A. Rassat, and A. Rousseau, Bull. SOC. chim. Frame, 1966, 1, 428.63 R.H. Martin, N. Defay, and F. Geerts-Evrard, Chimia, 1966, 20, 117.64 S. Forsen and R. A. Hoffman, J . MoZ. Spectroscopy, 1966, 20, 168.65 K. Takahashi, T. Kanda, F. Shoji, and Y. Matsuki, Bull. Res. Inst. Non-Aqu.6 6 R. Steinmetz, W. Hartmann, and G. 0. Schenck, Chem. Ber., 1965, 98, 3854.67 K, Tori, A. Aono, Y. Hata, T. Tsuji, R. Muneyuki, and H. Tanida, Tetrahedron68 K. L. Williamson, T. Howell, and T. A. Spencer, J . Amer. Chem. SOC., 1966, 88,G 9 A. Dieffenbacher and W. Von Philipsborn, Helv. Chim. Acta, 1966, 49, 897.70 H. Frischleder and G. Biir, MoZ. Phys., 1966, 11, 359.71 P. C. Myhre, J. W. Edmunds, and J. D. Kruger, J . Amer. Chem. SOC., 1966, 88,72 M. Tanabe and G. Detre, J . Amer. Chem. SOC., 1966, 88, 4515.L. A. Paquette and J.H. Barrett, J . Amer. Chern. Soc., 1966, 88, 1718.Sol. Tohoku University, 1965, 15, 1.Letters, 1966, 1, 9.325.2459FEENEY : NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY 249in an optically active solvent and this difference can be observed in theirn.m.r. spectra.73, 7 4 Thus, when a racemic mixture of 2,2,2-trifluoro-l-phenylethanol (11) is examined in an optically active solvent the fluorineRresonances appear as two doublets of equal intensity each doublet beingassociated with an enantiomer.73 The optical purity of compounds whichare dissymmetric, as airesult of deuterium substitution, has been e~tirnated.'~By examining asymmetrically diastereomeric deuteriated molecules, one canfollow the course of substitution reactions at carb0n.7~ Useful methods ofcharacterising alcohols have been suggested.For example, alcohols havebeen classified by conversion to their trifiuoroacetyl derivatives and thenexamining the 19F spectra of the trifluoroacetate esters which have shiftscharacteristic of the alcohol considered.77 Phenolic groups can be detectedby observing the disappearance of their proton absorption when the smallwater impurity band in the spectrum is irradiated in a frequency sweepdouble resonance experiment .78 Absolute signs of coupling constants havebeen determined by solvent effects 79 and by relaxation-time measurements.80Solid cyclohexyl chloride with the chloro-substituent in the equatorialposition has been separated out by slowly cooling through its melting point.Examination of its n.m.r.spectrum at - 151 O in pre-cooled CD,CDCI demon-strates the isolation of a single conformer.8lExperimental Techniques.-The method of time-averaging usingspectrum accumulation for sensitivity enhancement has been considered indetail;82 only in special cases is the signal to noise ratio improved by afactor exactly equal to the square root of the number of scans. Successfuln.m.r. investigation of a gas-chromatograph single pass fraction usingspectrum accumulation techniques has been rep0rted.8~ Frost and Hallhave studied the problems encountered in using external spherical referencecells.84 A capillary filled with a mixture of water, methanol, and hydro-chloric acid can be used for accurate n.m.r. temperature calibration (&0.2")over the temperature range -25 to Richards and co-workers have73 W.H. Pirkle, J . Amer. Chem. SOC., 1966, 88, 1837.7 4 T. G. Burlingame and W. H. Pirkle, J . Amer. Chem. SOC., 1966, 88, 4294.75 M. Ravan and K. Mislow, Tetruhedron Letters, 1966, 33, 3961.7 6 C. A. Kingsbury and W. B. Thornton, J . Amer. Chem. SOC., 1966, 88, 3159.7 7 S. L. Manatt, J . Amer. Chem. Soc., 1966, 88, 1323.78 J. Feeney and A. Heinrich, Chem. Corm., 1966, 295.78 C. L. Bell and S. S. Danyluk, J . Amer,Chem. SOC., 1966, 88, 2344,E. L. Mackor and C . Maclean, J . Chem. Phys., 1966, 44; 64.F. R. Jensen and C. H. Bushweller, J . Amer. Chem. SOC., 1966, 88, 4279.R. R. Ernat, Rev. Sci. Instr., 1965, 36, 1689.83 R. E. Lundin, R. H. Elsken, R. A. Flath, N. Henderson, T.R. Mon, and R.84 D. J. Frost and G. E. Hall, Mol. Phys., 1966, 10, 191.85 R. Duerst and A. Merbach, Rev. Sci. Instr., 1965, 36, 1896.Teranishi, Analyt. Chem., 1966, 38, 291250 ORQANIC CHEMISTRYinvestigated the possibility of increasing signal to noise by using nuclear-electron Overhauser effects ; in solutions containing free radicals (such astri-t-butylphenoxyl radicals) when the electron resonance is saturated,dramatic changes in the signal to noise in the nuclear resonance spectrum ofthe solvent may be observed, as a result of the nuclear relaxation processbeing influenced by scalar or dipolar coupling between the nuclei andelectrons.86 [19F (ref. 87), 13C (ref. 88), 31P (ref. 89).] Overhauser studieshave been reported with signal to noise improvements of up to 35 : 1.Therehas been a report of a new double resonance method for detecting connectedtransitions in complex spectra in which a monitoring radio frequency (r.f.)is held at exact resonance for a chosen line, q, in the spectrum, while a,second r.f. field is swept through the complete spectrum, both fields beinghigher than the saturation value.9* When the swept frequency passesthrough a transition with an energy level in common with the line v1 then atransient nutation of the swept transition is observed and hence all transitionsconnected with v1 can be observed. Successful homonuclear INDOR experi-ments have also been reported by Kowalewski and co-w0rkers.~1 1 5 N enrich-ment ( l 5 N has a spin value I = $) is becoming more widely used.92 Byexamining a keto-enol equilibria mixture of substituted anilides, theobserved 15N-H coupling provided a lower limit to the residence time ofthe proton on the nitr0gen.~3 In the low temperature lH resonance spectrumof highly purified liquid ammonia, one can detect the l5NH satellite spectrumfrom the 0.365% ofPartial deuteriation of compounds continues to be a popular means ofsimplifying their proton spectra by removing H-H spin splittings, particu-larly in kinetic studies where one is aided considerably if the observed lineshape variations can be made on simple absorptions.Thus the ring proton spectrum in p-nitrosodimethylanilhe 95 is con-Biderably simplified by examining the deuteriated compound (12) to facilitatethe investigation of the rotation about the C-NO bond.containing molecules in natural abundance.s486 R.A. Dwek, J. G. Kenworthy, D. F. S. Natusch, R. E. Richards, and D. J.Shields, Proc. Roy. SOC., 1966, A , 291,487; D. F. S. Natusch and R. E. Richards, Chem.Comm., 1966, 185; R. A. Dwek, J. G. Kenworthy and R. E. Richards, MoZ. Phys., 1966,87 E. H. Poindexter, J. R. Stewart, R. J. Runge, andD. D. Thornson, J . Chem. Phya.,88 D. F. S. Natusch and R. E. Richards, Chem. Comm., 1966, 579.89 R. A. Dwek and R. E. Richards, Chem. Comm., 1966, 580.J. A. Ferretti and R. Freeman, J . Chem. Phys., 1966, 44, 2054.91 V. J. Kowalewski, D. G. de Kowalewski, and E. C. Ferra, J. MoZ. Spectroscopy,1966, 20, 203.oa A. K. Bose and I. Kugajevsky, J . Arne?. Chem.SOC., 1966, $8,2325; E. D. Becker,H. T. Miles, and R. B. Bradley, ibid., 1965,87,5575; D. T. Clark and J. D. Roberts, ibid.,1966, 88, 745.93 G. 0. Dudek and E. P. Dudek, J . Amer. Chem. SOC., 1966, 88, 2407.94 T. J. Swift, S. B. Marks, and W. G. Sayre, J. Chm. Phys., 1966, 44, 2797.D5 P. K. Korver, P. J. Van der Haak, and Th. J. De Boer, Tetrahedron, 1966, 22,10, 539.1966, 44,4059.3157FEENEY: NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY 251b e t and co-workers 96 have further extended the technique by irradiatingat the deuterium frequency to remove unwanted small H-D splittings inthe proton spectrum, which then lends itself to a more exact kinetic analysis.The two [2H,,]cyclo-octane molecules (13) and (14) have been examined inthis way a t low temperatures.At about -140", both compounds give A13 proton spectra and the resultsare consistent with the boat-chair and/or the twist boat-chair, being themajor conformations for cyclo-octane.Similar conclusions have beenreached for mono-substituted cyclo-octanes.9~ Piperidine (15) and N-methylpiperidine, deuteriated as indicated in (15) have been investigateda t low temperature^.^^For piperidine, at --80", the a- and yprotons show a separate AB spectrumand similar results are obtained for the N-methylpiperidine. However thea-equatorial resonance for the N-methylpiperidine is 0.5 p.p.m. to higherfield than in pipsridine, which is taken as evidence that the nitrogen lonepair prefers an equatorial conformation in piperidine, but an axial conforma-tion in N-methylpiperidine. The methylene protons in benzyhethyl-sulphoxide, under conditions of H-D exchange, have been shown to exchangea t unequal rates.99studies of Intramolecular Dynamic Processes.-A great deal ofattention has been given to the study of rotation about bonds, interconver-sion in cyclic systems and inversion a t nitrogen atoms.In many instancesall the kinetic and thermodynamic parameters have been extracted fromthe n.m.r. results. The factors which can influence the accuracy of the deter-mination of rat4es of chernical exchange by high resolution and spin echon.m.r. measurements, have been critically considered.lW A method forfollowing rotational isomerism in molecules of type XCH,CHYZ has beensuggested ;lo1 by assuming (1) that the angular dependence of vicinal con-stants is given by J = Jo cos2 $, where $ is the dihedral angle, (2) that theequilibrium dihedral angle between gauche substituents in trisubstitutedacyclics is 65", and (3) that the small mole fraction of the conformer with Xgauche to both Y and Z is negligible then the ratio of the other two con-former populations is given by n/n' = [(J/J') - O.lSO]/[l - O*lSO(J/J')]where J and J' are the measured vicinal coupling constants.Numerous studies of rotation about the N-CO bond in amides and86 F.A. L. Anet and M. St. Jacques, J. Amer. Chem. SOC., 1966, 88, 2585.F. A. L. Anet and M. St. Jacques, J . Amer. Chem. SOC., 1966, 88, 2586.Q 8 J. B. Lambert and R. G. Keske, J. Amer. Chem. SOC., 1966, 88, 620.S.Wolfe and A. Rauk, Chem. Comm., 1966, 778.l o o A. Allerhand, H. S. Gutowsky, J. Jones, and R. A. Moinzer, J . Amer. Chew. Soc.,1966,88,3185.E. I. Snyder, J . Amer. Chem. SOC., 1966, 88, 1165.252 ORGANIC CHEMISTRYrelated compounds have been reported.102 Murray a'nd co-workers 10s haveprovided a very detailed and elegant example of conformational inter-conversion in their study of acetone diperoxide (16).On cooling to - 16-5", two sharp absorption bands for axial and equatorialmethyl groups are observed. The activation free energy, enthalpy, andentropy for the interconversion are calculated from the spectral temperaturedependence. Other studies of conformational interconversion in cyclicmolecules have been made by observing the temperature dependence of then.m.r.spectra of substituted cycl0hexanes,~0~ cis-decalins,lo5 perfluorocyclo-octane 106 (a rigid or slowly interconverting distorted-crown structure ispostulated), perfluorocyclobutane lo7 (very low-energy barrier to inter-conversion), cyclic trisulphides,lo8 N,O and S heterocyclic compo~nds,~0~and 3,5,7-cyclo- octatrienone . loInversion a t a nitrogen atom has been studied in dihydroquinolines,llIbenzylamines,ll2 and 2,2,3,3-tetrsmethylaziridine (17).l13Me7 (16)MeAt temperatures below 52" two different CH, absorptions are observed for(17); a t 52" the inversion rate is 25 sec.-l.lo* B. J. Price, R. V. Smallman, and I. 0. Sutherland, Chem. Comm., 1966, 319;T . H. Siddall, W. E. Stewart, and M. L.Good, ibid., p. 612; T. H. Siddall and R. H.Garner, Tetrahedron Letters, 1966,30, 3513; T . H. Siddall and C. A. Prohaska, J. Amer.Chem. Soc., 1966,88,1172; D. G. Gehring, W. A. Mosher, and G. S. Reddy, J. Org. Chem.,1966, 31, 3436; S. R. Johns, J. A. Lamberton, and A. A. Sioumis, Chem. Cmm., 1966,480; R. M. Hammaker and B. A. Gugler, J. Mol. Spectroscopy, 1965, 17, 356; G. R.Bedford, D. Greatbanks, and D. B. Rogers, Chem. Comm., 1966, 330; T. H. Siddall andR. H. Garner, Canad. J . Chem., 1966, 44, 2387; A. Mannschreck, Angew. Chem., 1965,77, 1032; L. F. Johnson, A. V. Robertson, W. R. J. Simpson, and B. Witkop, Azcstral.J. Chem., 1966,19, 116.lo3 R. W. Murray, P. R. Story and M. L. Kaplan, J . Amer. Chem. SOC., 1966,88, 526.lo4 S. Kabuss, A.Luttringhaus, H. Friebolin, H. G. Schmid, and R. Mecke, Tetra-hedron Letters, 1966,7, 719; R. J. Abraham and D. B. MacDonald, Chem. Comm., 1966,188; W. Reusch and D. F. Anderson, Tetrahedron, 1966, 22, 583; H. Friebolin, W.Faibt, and H. G. Schmid, Tetrahedron Letters, 1966, 12, 1317.lo5 J. T. Gerig and J. D. Roberts, J . Amer. Chem. SOC., 1966, 88, 2791.log A. Peake, J. A. Wyer, and L. F. Thomas, Chem. Cmm., 1966, 94.lo' R. P. Bauman and B. J. Bulkin, J. Chem. Phys., 1966, 45, 496.lo8 S. Kabuss, A. Luttringhaus, H. Friebolin, and R. Mecke, 2. Naturforsch., 1966,21b, 320.log J. M. Lehn and F. G. Riddell, Chem. Comm., 1966, 803; R. F. Farmer and J.Hamer, ibid., p. 866; P. J. Brignell, A. R. Katritzky, and P. L. Russell, ibid., p. 723;J. E. Anderson and J.C. D. Brand, Trane. Paraday SOC., 1966, 62, 39; R. Daniels andK. A. Roseman, Chem. Comm., 1966, 429; F. C. Riddell and J. M. fiehn, ibid., p. 376;W. D. Ollis and I. 0. Sutherland, ibid., p. 402.l 1 0 C. Canter, S. M. Pokras, and J. D. Roberts, J. Amer. Chem. SOC., 1966, 88, 4235.111 W. N. Speckamp, U. K. Pandit, P. K. Korver, P. J. Van der Haak, and H. 0.Huiman, Tetrahedron, 1966, 22, 2413.112 D. L. Griffitli and J. D. Roberts, J . Amer. Chem. Soc., 1966, 87, 4089.113 T. J. Bardos, C. Szantay, and C. K. Navada, J. Amer. Chem. SOC., 1965,87,5797FEENEY : NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY 253Solvent Ef€ects.-Dimethyl sulphoxide is enjoying increasing popularityas a solvent for hydroxyl containing compounds, because it suppresses theexchange rate and often allows the OH protons to participate in spincoupling.l14 However, this is not the case for alcohols with strongly electro-negative substitutents (e.g., 2,2,2-tri~hloroefhanol).~~~ For ortho-nitro-anilines, one observes a 0.5 p.p.m.downfield shift for the H-3 proton onchanging from DMSO to CDC1, solvent,ll6 this is because the solute isnormally intramolecularly hydrogen bonded, but the DMSO competes withthe nitro-group for the hydrogen bonding site, resulting in rotation of boththe amine and nitro-groups from the plane of the ring. Abraham and co-workers n' have shown how to calculate the solvent dependence of con-formational equilibria in substituted ethanes. Effects on spectra caused bychanging the solvent from an inert solvent to benzene have been measuredfor 6-lactones,ll8 methoxybenzenes 119 (benzene causes upfield shift ofCH30 resonance), quinones l2O and ll-oxo-steroids 1 2 1 and other com-pounds.122 Mechanisms for solvent-induced shifts have been ~0nsidered.l~~The usefulness of examining steroids in deuteriopyridine rather thandeuteriochloroform has been confirmed.124Conformational Studies.-By far the most outstanding advancemade in this field is the discovery that 13C resonance studies can provideuseful conformational information. The 13C shifts of the carbinol carbonsin cyclohexanol derivatives depend markedly on the orientation of theoxygen function ; in cis- and trans-4-t-butylcyclohexanols, the carbon withan axial OH group is 4.9 p.p.m.more shielded than that with an equatorialOH g r 0 ~ p .l ~ ~ DMSO is a popular solvent for conformational studies ofcyclohexanols.126 In this solvent a series of cis- and trans-isomers indicatedthat the axial OH protons are shielded more than those in equatorial positionsand H-C-OH spin coupling constants are larger for the OH equatorialsysterns.lz6 Booth127 has provided an extensive and useful summary ofeffects of alkyl substituents on the shielding of cyclohexanc ring protons.Conformational studies of cyclohexanes,12* 9 129 aldosesY130 deoxyhex~ses,~~~114 0. L. Chapman and R. W. King, J . Amer. Chem. SOC., 1964,86, 1256.115 J. G. Traynham and G. A. Knesel, J. Anzer. Chem. SOC., 1966, 87, 4220.116 I. D. Rae, Chem. Comm., 1966, 519.11' R.J. Abraham and M. A. Cooper, Chem. Comm., 1966, 588; R. J. Abraham andG. Di Maio, P. A. Tardelia, and C. Iavarone, Tetrahedron Letters, 1966, 2!5, 2826.119 J. H. Bowie, J. Ronayne, and D. H. Williams, J. Chem. Soc. ( B ) , 1966, 785.lZo J. H. Bowie, D. W. Cameron, P. E. Schutz, D. H. Williams, and N. S. Bhacca.121 D. H. Williams and D. A. Wilson, J. Chem. SOC. ( B ) , 1966, 144.122 T. Ledaal, Tetrahedron Letters, 1966, 15, 1653.lZs J. Ronayne and D. H. Williams, Chem. Comm., 1966, 712; P. Laszlo, Bull. SOC.lZ6 G. W. Buchanan, D. A. Ross, and J. B. Stothers, J. Arner. Chem. SOC., 1966, 88,126 C. P. Rader, J. Amer. Chem. SOC., 1966, 88, 1713.lZ7 H. Booth, Tetrahedron, 1966, 22, 615.128 N. C. Franklin and H. Feltkamp, Tetrahedron, 1966, 22, 2801.129 J.Reisse, J. C. Celotti, and R. Ottinger, Tetrahedron Letters, 1966, 19, 2167.13* R. U. Lemieux and J. D. Stevens, Camd. J. Chem., 1966, 44, 249,131 T. D. Inch, J. R. Plimmer, and H. 0. Fletcher, J. Org. Chm., 1966, 31, 1825.K. G. R. Pachler, and L. CavaUi, Mol. Phys., 1966, 11, 471.Tetrahedron, 1966, 22, 1771.chirn. France, 1966, 3, 1131.B. Hampel, and J. M. Kraemer, Tetrahedron, 1966, 22, 1601.4301254 ORGANIC CHEMISTRY~arbohydrates~l3~ cyclic sulphites,l33 N-methyl la~tams,’~~ 1,3- and 1,4-dioxans 135 and various diastereoisomers 136 with phenylethyl skeletons (theerythro-isomer usually has the larger JHHufC value).An&& of Spectra.-The use of computers in helping to analysesecond-order high resolution spectra is becoming more widespread.l57 Theten-spin system A,X,X’,A’, ( CF,CF,CF,CF,) has been analysed using aniterative approach with a computer.lS7 Analysis of spectra from X,AA’X’,systems has been extended to cases where the long-range coupling Jx,x# isn o n - ~ e r o .~ ~ ~ Sub-spectral analysis procedures have also been used exten-sively to analyse spectra: thus the lH and 19F resonance spectra of 1,2,3,5-tetrafluorobenzene have been analysed as an AA’XX’MR spin ~ystem,1~~and 2,6-dichlorofiuorobenzene and 1 -chloro-2,3-butadiene have been analysedas A,BX, spin systems.140 Group theoretical methods for analysingX,AA’X,’ systems have been shown to be more time consuming than thecomposite particle method of ana1y~is.l~~ A simplified method for analysingAA’BB’ spectra more directly has been described 142 which is also effectivewhen the spectrum contains overlapping lines. Snyder 14, has described aconvenient method for analysing high-resolution spectra of solutes dissolvedin liquid crystals in the nematic phase.Elegant examples of virtual couplingare provided in the lH spectra of geminal ethoxycyclotriphosphazati.ienes.144For example, in the proton spectrum of the tetraethoxydiphenyl compound(18) the methylene absorption is a triplet of quartets./ \Ph PhOn irradiation of the CH, absorption in a double resonance experiment, themethylene band becomes a triplet. The separation between the outer linesof the triplet gives [JPR + JPtH]; Thus we have virtual coupling involvingthe cross ring long-range coupling (JP)= w 0) because P and P‘ are stronglycoupled.132 G.E. McCasland, M. A. Naumann, and Lois J. Durham. J . Org. Chem., 1966,133 C. G. Overberger, T. Icurtz, and S. Yaroslavsky, J. Org. Chem., 1966, 21, 4363.134 R. M. Moriarty and J. M. Kliegman, Tetrahedron Letters, 1966, 9, 891.lS6 G. Pfundt and S. Farid, Tetrahedron, 1966, 22, 2237; G. Altona and E. Tavinga,ibid., p. 2275; J. Delmnu and J. Duplan, Tetrahechon Letters, 1966, 24, 2693; C. Y.Chen and R. J. W. Le FGvre, J . Chem. Soc. ( B ) , 1966, 544; M. Anto-mis, D. Tavernier,and F. Borremans, Bull. SOC. chim. belges, 196G, 75, 396.136 C. A. Kingsbury and W. B. Thornton, J . Org. Chem., 1966, 31, 1000.13’ W. D. Keller, T. R. Lusebrink, and C. H. Sederholm, J . Chem. Phys., 1966, 44,782; R.C. Hopkins, J . Mol. Spectroscopy, 1966, 20, 321.13* R. K. Harris and C. M. Woodman, MoZ. Phys., 1966,10,437.139 E. Lustig and P. Diehl, J . Chem. Phys., 1966, 44, 2974.140 R. C. Hirst, D. M. Grant, and E. G. Paul, J. Chem. Phys., 1966, 44, 4305.141 C. M. Woodman, Mol. Phys., 1966, 11, 109.1 4 2 T. K. Lim, A. Taurins, and M. A. Whitehead, Canad. J . Chem., 1966, 44, 1211.*33 L. C. Snyder, J . Chem. Phys., 1965, 43, 4041.114 C. Hewlett and It. A. Shaw, J . Chem. SOC. ( A ) , 1966, 56.31, 3079FEENEY : NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY 255Magnetic Non-equivalence Resulting from Molecdlar Asm-me@.-A review of magnetic I non-equivalence has andfurther examples of magnetic non-equivalence in methylene 146 and iso-propyl 147 groups attached to asymmetric centres have been cited.When ametbylene group is attached to an asymmetric centre [see (19)J the twomethylene protons will always be geometrically non-equivalent, even in thepresence of free rotation (equally populated rotamer states). This is becauseof the intrinsic asymmetry in the molecule.Snyder 146 has shown this chemical shift difference to be very solventdependent. Raban 148 has attempted to estimate the contribution to theshift difference arising from molecular asymmetry (as opposed to thatarising from non-equal rotamer populations) by examining the low temper-ature 19F spectra of CF,BrCHBrCl, where the rotamera can be frozen out.The contribution from molecular asymmetry was estimated to be about1 p.p.m.Mkcellaneons Strrdies.-From the many n.m.r.investigations carriedout, the following have been selected because they contain a substantialamount of useful n.m.r. data on general classes of compounds: aliphaticesters,lg9 amines,150 di- and tri-azanaphthalenes,l51 azophenols and quinonehy~hazones,~~~ cyclic-@-keto e~ters,l5~ cyclopropanes,l54 9,lO-dihydroanthra-cenes,l 55 fulvenes, 56 imidazo[ 1,2-u]pyrimidines,l57 2-indanones,f58 naphtha-lenes, 159 naphthoquinones and naphthazarins,l60 NN-dimethylcarbamates,161N-niltrosourethans,lG2 AT-substituted methylamines,163 N-substituted piper-idines, pentadiynes, lG5 phenazines, 66 piperidin-4-ols,l87 pteridines,146 L. Martin and J. Martin, Bull. SOC. chim. France, No. 6, 1966, 2117.146 E. I. Snyder, J .Amer. Chem. SOC., 1966, 88, 1155.14' H. J. Jalrobsen, P. Madsen, and S. 0. Lawesson, Tetrahedron, 1966, 22, 1851.lP8 M. Raban, Tetrahedron Letters, 1966, 27, 3105.14* 0. Rosado-Lojo, C. I<. Hancock, and A. Danti, J. Org. Chem., 1966, 31,lSo William R. Anderson, jun., and Robert M. Silverstein, Analyt. Chem., 1965,161 W. L. F. Armarlgo and T. J. Batterham, J. Chern. SOC. ( B ) , 1966, 751.15* B. L. Kaul, P. M. Nair, A. F. R. Rao, and K. Venkataraman, Tetrahedrm Letters,lSa S. J. Ehoads, J. Org. Chem., 1966, 31, 171.lS4 C. H. de Puy, F. W. Breitbeil, and K. R. d0 Bruin, J . Amer. Chem. Soc., 1966,166 W. Carruthers and G. E. Hall, J . Chem. Soc., ( B ) 1966, 861.lS6 A. S. Kende, P. T. Izzo, and P. T. MacGregor, J . Amer. Chem. Soc., 1966, 88,16' W.W. Paudler and J. E. Kuder, J . Org. Chem., 1966, 31, 809.158 E. J. Moriconi, J. P. St. George, and W. F. Forbes, Canad. J . Chern., 19G6,44,759.lfi9 F. Bell and K. R. Buck, J . Chem. SOC. (C), 1966, 904.16* R. E. Moore and P. J. Scheuer, J . Org. Chem., 1966, 31, 3272.161 T. M. Valega, J. Org. Chem., 2966, 31, 1150.16* R. A. Moss, [retrahedron Letters, 1966, 7, 711.l b S M. Freifelder, R. W. Mattoon, and R. W. Kriesse, J . Org. Chem., 1966, 31,lU4 C. M. Lee, A. H. Beckett, and J. I<. Sugdea, Tetrahedron, 1966, 22, 2721.H. Taniguichi, I. M. Mathai, and S. I. Miller, Tetrahedron, 1966, 22, 867.166 Yutaka Morita, Chem. Pharm. Bull. (Tokyo), 1966, 14, 419.16' A. F. Caay, Tetrahedron, 1966, 22, 2711.166 A. Dieffenbacher, R. Mondelli, and W.von Philipsborn, Helv. Chim. Acta, 1966,1899.37, 1417; I. D. Rae, Austral. J . Chem., 196G,19, 409.1966, 32, 3897.88, 3347.3369; M. Rabinovitz, I. Agranat, and E. D. Bergrnann, Tetrahedron, 1966, 22, 225.1196.49, 1355256 ORGANIC CEEMISTRYpyrazoles, 169 pyrroIes, 70 quinazolines, l 7 1 steroids, lq2 styrenimines, 1'3 taxin-ine and derivatives,l7* tetracyclic diterpenoids, l75 tetracyclines l 7 6 andtetranortriterpenoids,1'7 triterpene~,~'~ urethanes 179 and unsaturated mono-and polycyclic compounds.~~O-18~Interesting n.m.r. studies have also been carried out on isomers of bisde-hydro[ 12lannulene and biphenylene,lS4 trimethyltropilidenes,186 bridgedpolycyclic compounds,186 and paracyclophane~.~~~ lH resonance studies on7-substituted 7J2-dihydropleiadenes 188 (20) indicate that the substituentprefers the axial conformation. Studies of the conformational interconver-sion in the 7-membered 'boat' ring have been carried out.H OAc -LCarbonium Ions.-J9F resonance measurements have been used tocharacterise the recently prepared phenylfluorocarbonium ion (2l).lS9.In thelow-temperature 19F resonance spectrum of (21), a triplet (JHB = 1 c./sec.)IBS L. G. Tensmeyer and C. Ainsworth, J. Org. Chem., 1966, 31, 1878.170 K. J. Morgan and D. P. Morrey, Tetrahedron, 1966, 22, 57.171 A. R. Katritzky, R. E. Reavill, and F. J. Swinbourne, J. Chem. SOC. (B), 1966,351.17* A. T. Glen, W. Lawrie, and J. McLean, J . Chem. SOC. (C), 1966, 661; G. Nathan-sohn, G. Winters, and A. Vigevani, Uazzetta, 1965, 95, 1338; C.H. Robinson and P .Hofer, Chem. and Ind., 1966, 9, 377; G. F. H. Green, J. E. Page, and S. E. Staniforth,J . Chem. Soc., 1965, 7328; K. K. Pivnitsky, I. V. Torgov, Tetrahedron, 1966,22, 1407;B. Hampel and J. M. Kraemer, ibid., p. 1601.178 S . J. Brois and G. P. Beardsley, Tetrahedron Letters, 1966, 42, 6113.174 M. C. Woods, K. Nakanishi, and N. S. Bhacca, Tetrahedron, 1966, 22, 243.176 J. R. Hanson, Tetrahedron, 1966, 22, 1701.M. S. Von Wittenau and R. K. Blackwood, J. Org. Chem., 1966, 31, 613.J. D. Connolly, R. McCrindle, K. H. Overton, and J. Feeney, Tetrahedron, 1966,178 B. Tursch, R. Savoir, and G. Chiurdoglu, Bull. SOC. chim. belges., 1966, 75, 107;17s A. J. Bloodworth and A. G. Davies, J. Chem. SOC.(B), 1966, 125.180 J. I. Brauman, L. E. Ellis, and E. D. van Tamelen, J. Amer. Chem. SOC., 1966,lslK. G. Untch and D. C. Wysocki, J. Amer. Chem. SOC., 1966, 88, 2610.lg2 S. Castellano and K. G. Untch, J . Amer. Chem. SOC., 1966, 88, 4238.lS3 I. C. Calder and F. Sondheimer, Chem. Comm., 1966, 904.22, 891.J. C. Mani, Ann. Chim. (France), 1966, 11 12, 533.88, 848.R. Wolovsky and F. Sondheimer, J. AM. Chem. SOC., 1965, 87, 5720.J. A. Berson and M. R. Willcott, J. Amer. Chem. SOL, 1966, 88, 2494.lS6 S. J. Cristol, T. W. Russell, J. R. Mohrig, and D. E. Plorde, J. Org. Chem., 1966,1 8 ' D. J. Cram and R. C. Helgeson, J. Amm. Chem. Soc., 1966, 88, 3515.188 P. T. Lansbury, J. F. Bieron, and A. J. Lacher, J. Amr. Chem. SOC., 1966, 88,18s G. A. Olah, C.A. Cupas, and M. B. Cornimrow, J. Amer. Chem. Soc., 1966, 88,21, 581.1477; 1482.362HORSFIELD : ELECTRON SPIN RESONANCE 257deshielded by 61 p.p.m. compared with the fluorine nuclei in C,H,CF,Cl;this deshielding probably arises from the positive charge residing mainly onthe fluorine as indicated in structure (22). N.m.r. has been used t o obtainrelative stabilisation energies for several carbonium ions,lgO and to charac-terise their structures.l91 It is possible to follow the protonation of indolizinesby n.m.r. When the indolizines are unsubstituted at the 3-position, onlythe H-3 cation (23) is formed.lg2MeEquilibria Studies.-Such studies have been made in several systems,for example, keto-enol tautomerism in &diketonesy1Q3 cis-trans-isomerismin diazoketones 194 and N-alkylformanilidesy195 and hydrogen bonding inalcohols lg6 and thi01s.l~~2. Part (ii).Electron Spin ResonanceBy A. Bornfield(Varian Associates La., Molemy Road, Wdton-on- Thaws, Surrey)A NUMBER of books 1, 2 and reviews3*4 on e.s.r. have appeared.has covered the literature from August 1963 to July 1965. Russell and co-workers 6 have reviewed the application of e.s.r. to structural and con-formational problems, with special reference to aliphatic semidiones.Schoffa has summarised applications of e.s.r. in biochemistry.Fkee Radicais in Solution.-The study of free radicals in solution con-tinues to attract attention and space does not permit a complete reviewof this work. Many new radicals and radical-ions have been observed andin most cases there is satisfactory agreement between the theoreticaln-unpaired-spin-density distribution, calculated by molecular orbital (MO)theory, and experimental n-spin densities derived from the hyperfinesplitting constants.lgO A.E. Young, V. R. Sandel, and H. H. Freedman, J . Amer. Chem. SOC., 1966,88,4632.lS1 G. A. Olah and M. B. Comisarow, J . Amer. Chem. SOC., 1966, 88, 4442.lea M. Frazer, S. McKenzie, and D. H. Reid, J . Chem. SOC. ( B ) , 1966, 44.IS3 G. Allan and R. A. Dwek, J . Chem. SOC. ( B ) , 1966, 161.l g P F. Kaplan and 0. K. Meloy, J . Amer. Chem. SOC., 1966, 88, 950.lgS A. J. R. Bourne, D. G. Gillies, and E. W. Randall, Tetrahedron, 1966, 22, 1825.lg6 J. Feeney and S. M. Walker, J . Chem.SOC. (A), 1966, 1149.lg7 S. H. Marcus and S. I. Miller, J . AMT. Chm. SOC., 1966, 88, 3719.EargleM. Bersohn and J. C. Baird, “An Introduction to Electron Paramagnetic Reso-a C. P. Poole, jun., “ Experimental Techniques in Electron Spin Resonance,” Wiley‘ M. T. Jones and W. D. Phillips, Ann. Rev. Phys. Chem., 1966,17, 323.CI (3. Schoffa, Chimia (Switz.), 1966, 20, 165.nance, w. A. Benjamin, New York, 1966.and Sons, London, 1966.D. R. Eargle, jun., Ann. Rev. Analyt. Chm., 1966, 371.G. A. Russell, E. T. Strom, E. R. Talttty, K. Y. Chang, R. D. Stephens, and M. C.Young, Rec. Chm. Progr., 1966, 27, 3258 ORGANIC CHEMISTRYSeveral free radicals containing phosphorus have been prepared 7 andthe phosphorus splittings reported and discussed.A series of neutralradicals in which boron is stabilised in unusual oxidation states by chelationhave been made.* The neutral radical and cation-radical of phenothiazinehave been obtained and Lhoste and Tonnard lo suggest that the observedhyperfine structure of the cations, of phenothiazine and phenoxazine areconsistent with a planar structure. The major triplet, with a splitting of5.4 Q, in the e.s.r. spectrum of hexamethylbenzene dissolved in sulphuricacid, suggests that radical produced is the hexamethylbenzyl cation.11Several dianion radicals have been observed.l2A number of semiquinone ions related to pyracycloquinone have beenmade, which demonstrate the existence of the pyracyclocyclone aromaticsystem.13 The bridged cyclodecapentaenes, 1,6-methano- and l,g-oxido-cyclodecapentaene give stable radical-anions and the experimental unpaired-spin distribution is in essential agreement with predictions based upon MOtheory.14Russell and his co-workers have continued their work on semidionesin solution, reporting the e.s.r.spectra from aryl and heterocyclic sub-stituted semidiones. They have shown that the spectrum originally attri-buted to acetophenone ketyl is probably due to l-phenylpropane-P,2-semidione. l5 Allendorfer and Rieger have identified the radicals obtainedby electrolytic reduction of tri- and di-nitromesitylene and dinitrodureneas nitroamine anions corresponding to the reduction of one nitro-group.The complete analyBis of their hyperke structure is reported.16The e.s.1.spectrum of l'o-enriched p-benzosemiquinone has been re-ported. The 170 hyperfine splitting, of about 9 Q, is solvent dependentand its sign, determined from hyperfine linewidth variations, is found to bsnegative.17 The transfer of spin density across oxygen l 8 and nitrogen l9bridges in p-substituted phenoxy-radicals has been confirmed from thehyperfine structure, and spin density on the bridge oxygen atom has beenobserved by Rieker by l7O substitution.lsA number of nitroxide radicals have been studied, particularly by Rassat7 A. H. Comley and M. H. Hnoosh, J. dmer. Ckern. Soc., 1966, 88, 2595; W. M.M. A. Kuck and G. Urry, J . Amer. Chem. Soc., 1966, 88, 426.B. C. Gilbert, P. Hanson, R. 0. C. Norman, and B. T. Sutcliffe, Chem. Cornm.,Gulick, jun., and D.H. Goske, ibid,, p. 2928.1966, 161.lo J. N. Lhwte and F. Tonnard, J. China. phys., 1966, 63, 678.l1 R. Hulme and M. C. R. Symons, J. Chem. SOC. ( A ) , 1966, 446.la R. I. Shapiro, V. M. Kazakova, and G. M. Lipkind, Zhur. strukl. Kkirn., 1966,7, 612; E. G. Janzen and J. G. Pacifici, J . Anper. Chem. SOC., 1985, $7, 5504; E. G.Jmzen, J. G. Pacifici, and J. L. Gerlock, J. Phys. Chem., 1966, 'SO, 3021.l3 B. M. Trost and S. F. Nelson, J. Amer. Chem. SOC., 1966, 88, 2876.l4 F. Gerson, E. Heilbronner, W. A. Boll, and E. Vogel, Helv. China. dcta., 1965,l6 0. A. Russell, E. T. Strom, E. R. Talaty, and S. A. Weiner, J. Amer. Chmn. SOC.,l6 R. D. Allendorfer and P. H. Rieger, J. Anter. Chent. Soc., 1966, $8, 3711.l7 W. M. Gulick, jun., and D.H. Geske, J. Amer. Chem. Xoc., 1966, 88, 4119; B. L.la A. Bieker, 2. Natzlrforsch., 1966,21b, 647; D. A. Bolon,J. Amm. Chem.Soc., 1966,A. Rieker, K. Sheffler, R. Mayer, B. Nm, and E. Miiller, Annalen, 1966,693,lO.48,1494.1966, $8, 1998; E. T. Strom, 0. A. Russell, and J. H. Schoeb, ibid., p. 2004.Silver, Z. Luz, and C. Eden, J. Chem. Phys., 1966, 44, 4258.88, 3148HORSFIELD : ELECTRON SPIN RESONANCE 259and his co-workers,20 who show that the hyperhe structure from protons Bto the NO group gives information about the conformation of the radicals.Blackley 2 1 has suggested that nitroxide radicals with two difluoromethylenegroups bonded to the nitrogen atom form a general class of stableradicals.Accurate measurements of the g-factors of 20 aromatic free-radicalshave been made22 and agreement with Stone's theory 23 is good exceptfor radicals where Jahn-Teller distortions are expected.Norman andPritchett have used g-factors to distinguish between radicals with similarhyperfine structure. Using g-factors they have shown that the radicalobtained by the reaction of OH radicals with butane-2,3-diol in a flowsystem is CH,COfiHCH, and not CH,6(OH)CH(OH)CH,.24McKinney and Geske 25 have observed conformational isomers of thetetraisopropyhitrobenzene anions, which are in thermodynamic equilibriumin solution. These conformers arise from two angular orientations of thenitro-group with respect to the plane of the benzene ring, manifested bytwo distinct nitrogen coupling constants.A useful summary of previouse.s.r. work on coilformational isomerism is given in this Paper.25 Variationin the coupling constant of the 4-substituent, depending on the conformationof the radical, has been noted in a series of 4-substituted 2,6-di-t-butylphen-oxy radicals.26 The spectra of 9,lO-diphenylanthracene anion and cationradicals have been examined ; the best fit between experimental and theore-tical coupling constants is obtained by assuming angles of twist of about.60" between the phenyl groups and the anthracene plane.27 Similar re-lationships between the unpaired-spin-density distribution and the con-formation have been noted in diarylmethyl radicals and diary1 ketyls. 28With the 1,2 : 5,6-dibenzocyclo-octatetraene and tetraphenylene radical-anions, however, Garst has found that non-planar and planar models givesimilar values for the calculated proton-coupling constants.29 The measuredhyparfine-splitting constants of the hexamethyl-3-radialene anion 30 arein agreement with those calculated on the basis of the structure in (1).The anion-radical of monohomocyclo-octatetraene is a homoaromatic ninen-electron system 31 and the observed hyperfine structure is consistentwith the structure in (2), with splittings of 16.8 G and 2.0 G for the twoprotons at C-9.2o G. Chapelet-Letourneux, H. Lemaire, and A. Rassat, Bull. Soc. chim. France,1965, 3283; R. M. Dupeyre and A. Rassat, J. Amer. Chem. SOC., 1966, 88, 3180; A. B.Sullivan, J. Org. Chem., 1966, 81, 2811.21 W. D. Blacklcy, J.Amer. Chem. Soc., 1966, 88, 480.22 B. G. Segal, M. Kaplan, and G. K. Fraenlrel, J . Chem. Phys., 1965, 43, 4191.2s A. J. Stone, Mol. Phys., 1963, 6, 509; 19G4, 7, 311.24 R. 0. C. Norman and R. J. Pritchett, Chem. and Ind., 1965, 2040.25 T. M. McKinney and D. H. Geske, J . Chenz. Phys., 1966, 44, 2277.e e R. W. Kreilick, J. Amer. Clmn. Soc., 1966, $8, 5284.L. 0. Wheeler, K. S. V. Santhanam, and A. J. Bard, J . Phys. Chent., 1966,70,404.ea J . de Jong, K. H. Fleurke, and R. van Hardeveld, Rec. T n ~ v . china., 1966,85,284;2B J. F. Garst, Mol. Phys., 1966, 10, 207.F. Garson, E. Heilbronner, and G. Kobrich, He7v. Chim. Ach., 1965, 48, 1525.31 R. Rieke, M. Ogliaruso, R. McClung, and S. Winstein, J. Amer. Chem. Soc., 1966,H. R. Falle and F.C. Adam, Canad. J. Chem., 1966,44, 1387.88, 4729260 ORGANIC CHEMISTRYHTransient radical studies. Relatively little work has been done on photo-chemical reactions because the stationary concentration of radical-inter-mediates during photolysis is often too small to be detected by e.s.r. Living-ston and Zeldes have overcome this limitation by combining the use ofan intense U.V. source with a flow system for continuously replenishing thereactants inside the e.s.r. cavity.32, 33 Radicals of the type RbHOH fromirradiated alcohols and aqueous alcohols, both containing small amountsof hydrogen peroxide, have been observed in large concentration. Theradicals are formed by a-hydrogen abstraction by OH radicals from thephotolysed hydrogen peroxide, as observed in Dixon and Norman’s work 34where the OH radicals were generated by reaction between Ti3+ and hydrogenperoxide.With irradiated aqueous alcohols,33 the concentration of radicalsformed by abstraction of p-hydrogens is enhanced. Photolysis of ally1alcohol gives rise to two radicals which are geometric isomers, with relativeabundances depending on temperature. 32 With acetone, 32 in the presenceof a hydrogen donor, both radicals were observed.hvCH,-CO-CH, + RH --+ (cH,),~oH + iiA number of transient radicals generated in flow systems have beenreported. Lucken has observed abstraction of hydrogen atoms by OHradicals from the carbon adjacent to the oxygen in methyl- and ethyl-estersof phosphoric and phosphinic a~ids.~5 In the 1-electron oxidation of somediols, radicals of the type HO-C-h-X where X is a good anionic leavinggroup, undergo elimination to give O=C- C< radicals.This reactionIaccounts for the formation of 6H,CHO from the reaction of OH with ethyleneglyco1.36 E.s.r. provides information about the conformational preferencesof iminoxy-radicals, formed by 1 -electron oxidation of benzaldoximes andoximes by ceric sulphate in a flow system, since the values of the hyperhesplittings are strongly dependent on the geometry of the radical.37 Theoxidation of aryl sulphinic acids with ceric sulphate gives rise to short-’ . ‘3a R. Livingston and H. Zeldea, J . Chena. Phys., 1966, 44, 1245; 1966, 45, 1946.33 R. Livingston and H. Zeldes, J . Amber. Chenz. Soc., 1966, 88, 4333.34 W.T. Dixon and R. 0. C. Norman, J . Chem. Sm., 1963, 3119.36 E. A. C. Lucken, J . Chem. SOC. (A), 1966, 1354 and 1357.s6 A L. Buley, R. 0. C. Norma, and R. J. Pritchett, J. Chcrn. SOC. (B), 1966, 849.37 B. C. Gilbert and R. 0. C. Norman, J . CIwm. SOC. (B), 1966, 722HORSFIELD : ELECTRON SPIN RESONANCE 261lived arylsulphonyl radicals, RSb,, which show only weak hyperfine splittingfrom the ortb-hydrogens.S8Binsch and Ruckhardt 39 have observed the radical C,H&“N, asexpected in phenylations with N-nitrosoacetanilides which are thought toproceed via the diazoanhydride intermediate, according to the reaction :HNitroxide radicals have been detected by reaction of NO with diazo-com-pounds and oximes in acetone solution, confirming their role as intermediatesin the formation of nitrimines and azine-bis-oxides by this reaction.40Nitroso-compounds often give e.s.r.signals characteristic of nitroxidea,especially on irradiation, and it has been shown that these are probablydue to dialkyl nitroxides.*lIon-pairing between radicalanions and their alkali gegen-ions is well-established. From alternatingline broadening in the hyperfine structure for certain ion-pair systems suchas potassium-p-benzosemiquinone, it has been concluded that two kinds ofion-pairs, which differ in their degree of solvation and metal-moleculeproximity, can exist in eq~ilibrium.4~ An alternating line-width effect inthe trinitromethyl dianion spectrum has been attributed to rapid inter-change between three equivalent non-planar conformations which modulatesthe 14N hyperfine-splitting constant.The temperature dependence oflinewidth gives an activation energy of 6.5 kcal./mole for the dynamicprocess.4s Electron exchange between p-dinitrobenzene and its negativeion has been examined a t low concentrations where broadening of thehyperfine lines is observed and a t high concentrations where “exchange-narrowing ” causes the spectrum to collapse to a single line; quantitativeagreement for the rate constant of exchange is obtained in both cases.44N.m.r. of free ~ a d i ~ a l s . The conditions under which n.m.r. spectra oforganic free-radicals can be observed, have been discussed. N.m.r. spectra areuseful for determining small hyperfine-coupling constants which are below thelimit of resolution of an e.s.r.spectrometer and the sign as well as the magni-tude of the coupling is obtained.45 Electron-transfer reactions betweena diamagnetic molecule and its paramagnetic anion modifies the n.m.r.Line width eflects in hyperfine structure.38 M. McMillan and W. A. Waters, J. Chem. SOC. ( B ) , 1966, 422.30 G. Binsch and C. Ruckhardt, J. Amer. Chem. Soc., 1966,88, 173.40 0. L. Chapman and D. C. Herbert, Chm. Comm., 1966, 242.42 M. P. Khakhar, B. S. Prabhananda, and 31, R. Das, J. Chem. Phys., 1966, 45,2327; P. B. Ayscough and F. B. Sargent, J. Chem. SOC. ( B ) , 1966, 900; N. Hirota andR. Kreiliclr, J. dmer. Chem. Soc., 1966, 88, 614.4s A. Hudson, C. Lagercrantz, and G. R. Luckhurst, MoZ.Phys., 1966, 11, 321.44 T. A. Miller, R. N. Adam, and P. M. Richards, J . Chem. Phys., 1966, 44, 4022.45 K. H. Hausser, H. Brunner, and J. C. J o c h h , MoZ. Phys., 1966, 10, 253.E. T. Strom and A. L. Bluhm, Chem. Cmm., 1966, 115262 ORGANIC CHEMISTRYspectrum of the molecule; line broadening provides information about therate of electron exchange and the line shift is related to the unpaired spindensity a t the proton. The theory has been developed and applied to electronexchange between p-xylene and p-diethylbmzene and their radical-anions.46Free Radicals in Solids.-Many studies of radicals formed by high-energy irradiation of compounds in rigid glasses at 77 O K have been reported.With pyridine, the radical cation is produced. The spectrum is dominatedby a triplet splitting of 30 a from the nitrogen atom.As the temperatureis raised, a second radical is formed by addition of a hydrogen atom to~yridine.~' In X-irradiated mixtures of benzene and methyl or ethylalcohol, the hyperfine structure of the radicals has been analyscd by selectivedeuteriation. It has been shown that irradiation liberates the hydroxylhydrogen from the alcohol, which either adds to benzene forming the cyclo-hexadienyl radical or abstracts an a-hydrogen from the alcohol formingthe corresponding radi~al.~g The formation of phenylcyclohexadienyl frombiphenyl, however, is slow a t 7 7 " ~ . * ~ In the y-irradiation of aliphatic andaromatic ketones in alcohol glasses,50 it is thought that their negative ionsare formed and these react with the substrate forming radicals of the typeIn U.V.irradiated polyolefins a t 7 7 " ~ ~ allryl radicals are observed butnone remain when the sample is warmed to room temperature. The radicalsgenerally correspond to the pendant group where side chains are present,such as -CH2CH(CH2)CH2- in poly~ropylene.~~ The main effect ofionising radiation on polytetrafluoroethylene oxide is scission of the main chainto give -CF2CF,6 radicals, although other species such as -06FCF20-are observed.52 Peroxy-radicals are identified on admission of air to thesample.When 1 ,l-diphenyl-2-picrylydrazyl (DPBH) is mixed with apparentlyinert materials such as magnesium carbonate, there is a loss of unpairedspins dependent on the material and the method of mi~ing.5~ This showsthat the use of dilute DPPH mixtures as standard samples for measuringunpaired-spin concentrations by e.8.r.is questionable.Free radicals have been identified in y-irradiated single crystals ofsubstituted malonic acids RCH( C02H),. In general two radical speciesare observed.54 The stable radical product is Rb(CO,H),, but RkH(C0,H)formed by loss of a carboxyl group is alsc formed initially in high concentra-tion and other radicals are observed which are unstable at room temperature.R$OHR,.4 8 E. de Boer and C. MacLean, J . Chem. Phys., 1966, 44, 1334.4 7 K. Tsuji, H. Yoshida, and K. Hayashi, J. G'hem. Phya., 1966, 45, 2894; C. David,48 J. A. Leone and W. S . Koski, J . Amer. Chem. Soc., 1966, 88, 224.4 8 T.Shida and W. H. Hamill, J . Amr. Chem. SOC., 1966, 88, 3689.5 0 T. Shida and TV. H. Hsmill, J . Arne?. Chem. SOC., 1966,88, 3683.5 1 H. L. Browning, H. D. Ackerman, and H. W. Patton, J . Polymer Sci., A-1, 1966,52 P. Barnaba, D. Cordischi, A. Delle Site, and A. Mele, J . Chem. Phys., 1966, 44,5 3 K. H. Bar-Eli and K. Weiss, J . Phys. Chem., 1966, 70, 1677.5 4 N. Tamura, M. A. Collins, and D. H. Whiffen, Trans. Paraday Soc., 1966, 62,G. Gouskens, A. Verhasselt, P. Jung, and J. F. M. Oth, Mol. Phys., 1966, 11, 257.4, 1433.3672.2434HORSFIELD ELECTRON SPIN RESONANCE 263At 77'9, new radical species are formed in substituted malonic acids and inglycine by irradiation. These change irreversibly on warming up and are saidto be the negative ions of the molecules.5*~ 55 High-energy irradiation of fum-aric acid trapped in urea crystals produces the radical ( C02H)CH2CH(C02H)by addition of a hydrogen atom to the double bond.Analysis of the e.s.r.spectrum indicates restricted torsional motion about the Ccc-Cb bond witha torsional barrier of 2 k~al./mole.~~Using single crystals of pentafluoropropionamide, it is found thatCF,6FCONH2 is the radical resulting from radiation Thefluoromethyl group is freely rotating a t room temperature, but it assumesa non-rotating configuration by cooling to 77°K. The data for the couplingtensors of the a- and p-fluorines are consistent with previous work.58 Asimilar radical C126C0NH2 has been observed in irradiated dichloroacetamideand the chlorine hyperfhe-coupling tensors have been measured.59Oriented free-radicals have recently been examined in solution in liquidcrystals such as p-azoxyanisole. The advantage of this is that the hyper-fine lines remain sharp so that the hyperfine structure of oriented aromaticradicals, which normally cannot be resolved in single crystals because o fdipolar line broadening, can be studied. The perinaphthenyl radical hasbeen observed in the isotropic phase and nematic mesophass of p-azoxy-anisole. From the change in the splitting constants on passing into thenematic liquid-crystal phase, the signs of the hyperfine-splitting constantsof the protons and 13C can be obtained. The g-tensor and hyperfine-splittingtensors have been derived and these are in agreement with theoreticalestimates.60 The e.8.r.spectrum of Coppinger's free radical (3) has beeninterpreted by assuming that the phenyl rings are twisted 19" out of themolecular plane. The shifts in the proton coupling constants on passingfrom the isotropic to the nematic phases of p-azoxyanisole are consistentwith this interpretation.61Biradi~als and the triplet state.-Several Papers on biradicals haveappeared. Ryzhmanov and co-workers have synthesised biradicals withtwo hydrazyl groups and have studied the e.s.r. hyperfine structure for thecases corresponding to strong exchange and weak exchange between the twounpaired electrons. 62 Rassat and co-workers have synthesised nitroxidebiradicals and illustrated the spectral cases for strong and weak exchangeand also intermediate cases where the exchange coupling J is of the sameorder as the hyperfine coupling of the nitroxide nitrogen atom.63 The55 M.A. Collins and D. H. Whiffen, illol. Phys., 1966, 10, 317.6G C. Corvajja, J . Chem. Phys., 1966, 44, 1958.6 7 R. J. Lontz, J. Chem. Phys., 10G6, 45, 1339.6a F. Srygley and W. Gordy, Bull. Amer. Phys. Soc., 1965, 10, 507; M. T. Rogersand D. H. Whiffon, J . Chem. Phys., 1984, 40, 2662.5 9 RI. Rashiwagi, Bull. Chem. SOC. Japan, 1966, 39, 2051.6o H. R. Fnllo and G. R. Luckhurst, MoZ. Phys., 1966, 11, 299; S. H. Glarum andJ. H. Marshall, J . Chcm. Phys., 1966, 44, 2884.61 G. R Luckhurst, Mo2 Phys., 1966, 11, 205.6 2 Yu. M. Ryzhmanov, Yu. V. Yablokov, B. M. Kozyrev, R. 0. Matevosyan, andL.I. Stashkov, DokEady Akad. Nauk S.S.S.R., 1965,164, 1073.63 R. Briore, R. M. Dubeyre, H. Lemaire, C. Morat, A. Rassat, and P. Rey, BUZZ.SOC. chim. France, 1965, 3290264 ORGANIC CHEMISTRYexistence of biradicals can be positively demonstrated by e.8.r. observationsof the radicals dissolved in the nematic mesophase of a liquid crystal;each of the hyperfine lines is split into two because of the unaveraged zero-field 8plitting. No such effect is observed for m~noradicals.~~ Luckhursthas shown that an alternating linewidth effect observed with several ni-troxide biradicals, showing strong spin exchange, can be understood if thedominant relaxation mechanism is a modulation of the exchange couplingbetween the unpaired electrons.65Excited triplet states for phenyl-s-triazines have been demonstrated.The phosphorescence spectra and zero-field splitting parameters leads to theassignment (n,n*) for the lowest triplet state of phenyltriazines.ge Theexcited triplet-state of the azulenium cation, dissolved in a glass of tri-fluoracetic acid, has been observed.67 The phosphorescent states of severalpositive ions in orbitally-degenerate states have been proved.68 Phenal-enylium and triphenylcyclopropenylium cations are shown from theirzero-field splitting parameters to be distorted. The symmetrical propellerstructure which has been proposed for the triphenylmethyl cation is notconsistent with the electron resonance spectrum of the excited triplet stateat 77 The phosphorescent state of mesitylene, incorporated in orientedB-trimethylborazole crystals, also exists in three isomeric conformationswith lower than three-fold symmetry at 77 The coronene &-negativeion exists as a thermally excited triplet-state with a singlet-triplet excitationenergy of about 0.1 ev.The splitting parameter D of 580 a is about halfthat observed for the neutral coronene molecule.70Rabald and Piette, irradiating solvent glasses with plane polarisedlight, have demonstrated that orientation of the triplets of a number ofaromatic molecules occurs with respect to the main magnetic field H,.They have further shown that in triplet-triplet energy transfer from benzo-phenone to naphthalene in glasses, there is no orientation requirementbetween donor and acceptor.71 Photoselective excitation of triplet moleculesin rigid glasses with polarised light can be used to determine the orientationof the molecular-transition moments.72Triplet nitrenes have been generated in single crystals of organic azidesby photolysis, which produces the nitrene RN by elimination of molecularnitrogen. For p-fluorobenzenesulphonylnitrene, hyperfine structure fromnitrogen is 0bserved.7~The triplet state zero-field splitting parameters have been calculated for6 4 H.R. FalIe, G. R. Luckhurst, H. Lemaire, Y. Marechal, A. Rassat, and P. Rey,6 5 G. R. Luckhurst, MoZ. Phys., 1966, 10, 543.66 J. S. Brinen, J. G. Koren, and W. G. Hodgson, J. C h m . Phya., 1966, 44, 3095.67 D. J. Blears and S. S. Danyluk, J. Amer. Chem. Soc., 1966, 88, 3162.66 M.S. de Groot, I. A. 31. Hesselmann, and J. H. van der Waals, Mol. Phys., 1966,68 M. S. de Groot, I. A. M. Hesselmann, and J. H. van der Waals, Mol. Phys., 1966,70 M. Glasbeek, J. D. W. van Voorst, and G. J. Hoijtink, J . Chem. Phys., 1965, 45,7 1 G. P. Rabold and L. H. Piette, Photochem. and Pfwtobiol., 1966, 5, 733.7 2 J. M. Lhoste, A. Hang, and M. Ptak, J. Chem. Phys., 1966, 44, 648 and 654.73 R. M. Moriarty, M. Rahman, and G. J. King, J . Amer. Chem. SOC., 1966, 88, 842.0 .No1. Phys., 1966, 11, 49.10, 241.10, 91.1852SCOPES : OPTICAL ROTATORY DISPERSION 265several molecules.74 Murrell and HinchliEe have calculated triplet ground-states for the di-negative ions of decacyclene and triphenylben~ene.~~Excited triplet-states have been investigated for molecules of biologicalimportance, such as DNA75 and p0rphyrins.7~ It is shown that photo-reactions in ethanol solution of porphyrins and aromatic aminoacids at77 O K proceed via an excited triplet-~tate.~~Biological Applications.-A new technique for investigating biologicalmolecules by e.s.r.has been devised by McConnell. By attaching syntheticorganic free radicals ( I c spin labels ”) to biomolecules, chemical, structuraland kinetic information may be obtained from changes observed in thehyperhe structure of the attached radical.77 Various nitroxide radicalshave been used as spin labels.78 The method has been used to investigatestructural changes in haemoglobin on oxygenation V9 and in poly-L-lysineand bovine serum albumin 77, 78 which are related to variations in pH.2.Part (iii). Optical Rotatory Dispersion and Circular DichroismBy P. M. Scopes(Westfield College, London, N . W.3)THIS year has seen a large increase in the number of publications on opticalrotatory dispersion (0.r.d.) and circular dichroism (c.d.); more than 250papers have appeared and this section is necessarily selective. Detailedstudies have been made of chromophores absorbing below 280 mp, parti-cularly in aromatic and carboxyl compounds, and in addition there has beena marked increase in the use of 0.r.d. or c.d., with other physical methods,as a general tool in structural and stereochemical studies of natural products.More than 60% of these general applications have utilised ketones, since thecarbonyl chromophore has been studied more thoroughly than any other todate.Reviews have appeared on the applications of these techniques toorganic compounds and co-ordination compounds 2 and on magnetic opticala ~ t i v i t y ; ~ three symposia on 0.r.d. and c.d. have been held recently? Animportant note has appeared on the problem of artifacts in 0.r.d. curves.574M. Godfrey, C. W. Kern, and M. Karplus, J. Chrn. Phys., 1966, 44, 4459; C.Thomson, MoZ. Phys., 1966, 10, 309; 1966, 11, 19’7; J. N. Murrell and A. Hinchliffe,ibid., 1966, 11, 101.7s R. 0. Rahn, R. G. Xhulman, and J. W. Longworth, J. Chern. Phys., 1966, 45,2955.76 0. A. Azizova, Z. P. Gribova, L. P. Kayushin, and M. K. Pulatova, Photochem.and Photobiol., 1966, 5, 763.7 7 T.J. Stone, T. Buckman, P. L. Nordio, and 1%. M. McConnell, Proc. Nat. Acad.Sci. U.S.A., 1965, 54, 1010.78 0. H. GrifEth and H. M. Mcconnell, Proc. Nat. Acad. Sci. U.S.A., 1966, 55, 8.7g J. C. A. Boeyens and H. M. McConnell, Proc. Nat. Acad. Sci. U.S.A., 1966,56,22.P. CrabbB, I n d . chirn. belge, 1966, 31, 131; H. Ripperger, 2. Chem., 1966, 6, 161.R. D. Gillard, Progr. Inorg. Chem., 1966, 7, 215.A. D. Buckingham and P. J. Stephens, Ann. Rev. Phys. Chem., 1966, 17, 399.cf. Proc.Roy. SOC., 1967, A, 297, 1.R. A. Reanik and K. Yammka, Biopolynaers, 1966, 4, 242; cf. also H. Wynberg,(3. L. Hekkert, J. P. H. Houbiers, and H. W. Bosch, J. Amsr. Chem. SOC., 1965,87, 2635,on accuracy266 ORaANIC CHEMISTRYA cell has been designed for the measurement of low temperature o.r.d.,Band an alternative method has been suggested for the determination of c.d.7has been widely applied tothe study of saturated carbonyl compounds but considerable differences ofopinion have been expressed as to the precise shape and position of the nodalsurfaces.The present situation has been clearly discussed by Wagni6re.QIf the carbonyl compound is regarded as being a symmetric chromophoreperturbed by an asymmetric environment, then either an octant 8 , 10 orquadrant rule l1 may be derived. Approximate self-consistent field mole-cular orbital theory lo applied to methylcyclohexanones confirms the exis-tence and position of three nodal planes as originally suggested,* but on itgroup theory basis, and without recourse to particular models, Schellman l1has suggested that the fundamental regional rule for the carbonyl groupshould be quadrant. A quadrant rule is also favoured if a ketone is con-sidered to be inherently dissymmetric on account of charge-transfer inter-actions.12 An unambiguous theoretical answer to this problem requiresmore accurate wave functions than those a t present a~ailable,~ and detailedexperimental study of ketones perturbed in front octants would be of value.Two approaches l3,14 have been made to the theoretical calculation ofthe sign and magnitude of ketone Cotton effects.Amplitudes have beenpredicted for alkylated cyclohexanones in both stable (chair) and unstable(boat) conformations lS and show moderate agreement with experimentalvalues.For cyclopentanone rings the possible conformations have beendivided into three groups to which standard amplitudes may be ascribed.For a given cyclopentanone derivative calculated energy values are used todeduce the percentage of the molecules in each preferred conformation.14With one exception, the calculated amplitudes are in good agreement withthose determined experimentally. The same compounds have been studied l5by c.d. a t low temperature and here the conformation of least energy is morestrongly preferred.The conformation of ring A in various substituted steroids has beenclosely studied 16 and 0.r.d. has been used to establish the configuration ofketones derived from columbin,l7 from the eremophilane and rosane l9Carbonyl Chromophore.-The octant ruleG.Horsman and C. A. Emeis, Tetrahedron, 1966, 22, 167.W. Moffitt, R. B. Woodward, A. Moscowitz, W. Iuyne, and C. Djerassi, J . A w .G. Wagnii.re, J . Anaer. Chem. SOC., 1966, 88, 3937.' P. F. Arvedson and E. M. Larson, Inorg. Chem., 1966, 5, 779.Chem. SOC., 1961, 83, 4013.lo Y. H. Pao and D. P. Santry, J . Ainer. C h m SOC., 1966,88,4167.l1 J. Schellman, J. Chew+. Phys., 19G6, 44, 55.la 0. E. Weigang and E. G. Hiihn, J . Amer. Cliem. SOC., 1966, 88, 3673.la J. C. Tai and N. L. Allinger, J. Amer. Chem. SOC., 1966, 88, 2179.l4 C. Ouannes and J. Jacques, Bull. SOC. chim. Pmme, 1965, 3611.l5 C. Djerassi, R. Records, C. Ouannes, and J. Jacques, Bull. SOC. chim. France,1966, 2378.l6 35. Fhtizon, M.Golfier, and P. Laszlo, Bull. Soo. chim. Frunce, 1965, 3486; M.Gorodetsky, A. Yogev, and Y. Mazur, J . Org. Chm., 1966,31, 699; J . Joska, J. FajkoB,and F. germ, Coll. Czech. Chem. Comm., 1966,31, 2745.1 7 K. H. Overton, N. G. Weir, and A. Wylie, J . Chem. SOC. (C), 1966, 1482.1* L. H. Zalkow, A. M. Shaligram, S. Hu, and C. Djerassi, Tetrahedron, 1966,22,337.l9 C . Djerassi, B. Green, W. €3. Whalley, and C. G. de Grazia, J. C l m . SOC. (C),1966, 624SCOPES : OPTICAL ROTATORY DISPERSION 267skeletons, and from photodimerisation of piperitone. 2O The 0.r.d. of cyclo-butanone derivatives has been used to determine the absolute stereochemistryof the sesquiterpenes u- and p-bourbonene.21The c.d. curves of 5-oxofenchone and certain of its derivatives show twomaxima of opposite sign a t about 300 mp in polar solvents.22 The twomaxima cannot be due to conformational isomers since the ring system isrigid and it has been suggested that the maximum a t shorter wavelengthmay be attributed to a solvated complex.(The maximum a t longer wave-length is always of the same sign as that of the same compound in a non-polar solvent and may be attributed to the free carbonyl group.)Aromatic Chromophores.-The sign and magnitude of the aromatic Cottoneffect in simple flexible compounds 23 depends on the separation of thechromophore from the nearest asymmetric centre and the magnitude isenhanced if a particular conformation is stabilised by hydrogen bonding.The longer wavelengthlk, (260-270 mp) aromatic Cotton effects of somel-substituted indanes (1) have been compared 24 with those of the corres-ponding acyclic (2) compounds; benzylidene compounds (with the styrenechromophore) 25 have also been examined.The absolute configuration of (+ )-1 -fluoro- 12-methylbenzo[c]phenan-threne has been determined 26 by comparison of its c.d.spectrum withcalculated values of the rotational strength. The molecule is a segment of aright-handed helix when viewed in the direction of the mean molecular plane(3). The absolute configuration of the alkaloid calycanthine (4) has beendetermined by the coupled oscillator method 27 which promises to be ofconsiderable general value for natural products.Me HH Me(4)ao H. ZifTer, N. E. Sharpless, and R .0. Kan, Tetrahedron, 1966, 22, 3011.a1 J. Kfepinsbjr, Z. Samek, and F. germ, Tetrahedron Letters, 1966, 3209.2 2 D. E. Bays, G. W. Cannon, and R. C. Cookson, J . Chem. SOC. (B), 1966, 885.23M. Legrand and R. Viennet, Bull. SOC. chim. France, 1966, 2798; L. Verbit,24 J. H. Brewster and J. G. Buta, J. Amer. Cherra. SOC., 1966, 88, 2233.26 J. H. Brewster and J. E Privett, J Amer. Chem. SOC., 1966, 88, 1419.8e C. M. Kemp and S. P. Mason, Tetrahedron, 1966, 22, 629.a7 S. F. Mason and G. W. Vane, J. Chem. SOC. ( B ) , 1966, 370.S. Mitsui, and Y. Sende, Tetrahedron, 1966, 22, 753268 ORGANIC CHEMISTRYFurther Papers have appeared on 1 - benzyl-tetrahydroisoquinolines andaporphine alkaloids,28 and the relationships between the c.d. of these com-pounds and of linearisine (5) and the pro-aporphine type have been dis-cussed by Snatzke.2s The signs of the Cotton effects at m.240 mp and 290 mpmay be used to assign absolute configurations in this series. The absoluteconfigurations of some indole alkaloids have been correlated with the 0.r.d.of their N-acyl-derivatives,m and among the corynoxine (oxindole) group theconfigurations of the spiro-atom may be determined.sl Two Papers haveappeared on absolute configurations in lycorine and related compounds 32and on alkaloids of the heteroyohimbine 33 and morphine series.34Porphyrim give extremely complex 0.r.d. curves ; an empirical correlationhas been made 35 between the 0.r.d. curves and the nature and position of thesubstituents on the aromatic system.Unsaturated Compounds.-An important note 36 has been published onthe c.d.of gliotoxin in which the cisoid diene system is known (X-ray) to be ina left-handed helix (chirality H).37 Gliotoxin gives a positive c.d. maximumat 270 mp and thus appears to contradict Moscowitz' rule 38 concerning thec.d. and helicity of skewed dienes. Low temperature c.d. has been used tostudy the conformational equilibrium in a-phellandrene. 39Three Papers on the 0.r.d. or c.d. of isolated olefinic double bonds havealso appeared. 40Chromophoric Derivatives.-For chromophores absorbing below 200 mp(-OH, -NH2) it is generally necessary to study derivatives having Cottoneffects in the accessible wavelength region. N-Salicylidene derivatives ofamines, 41 and the N-thiobenzoyl derivatives of a-amino-acids 42 have beenstudied extensively.A very detailed account of the low temperature c.d.of various chromophoric derivatives of alcohols and amines has appeared. 43Sulphur Compounds.-A study of steroid episulphides and other sulphurderivatives has given rise to a generalised sector rule relating the sign andJ. C. Craig, M. Martin-Smith, S . K. Roy, and J. B. Stenlake, Tetrahedron, 1966,22, 1335; N. S . Bhacca, J. C. Craig, R. €3. F. Manske, S. K. Roy, M. Shamma, andW. A. Slusarchyk, ibid., p. 1467; S. M. Albonico, J. C o d , A. M. Kuck, E. Sanchez,P. M. Scopes, R. J. Swan, and M. J. Vernengo, J . Cheno. SOC. (C), 1966, 1340.29 G. Snatzke and G. Wollenberg, J . Chem. SOC. (C), 1966, 1681.W. Klyne, R. 5.Swan, B. W. Bycroft, and H. Schmidt, Helv. Chim. Acta, 1966,49, 833.31 J. L. Pousset, J. Poisson, and M. Legrand, Tetrahedron Letters, 1966, 6283.32 K. Kotera, Y . Hamada, K. Tori, K. Aono, and K. Kuriyama, Tetrahedron Letters,1966, 2009; K. Kotera, Y. Hamada, and R. Mitsui, ibid., p. 6273.33 N. Finch, W. I. Taylor, T. R. Emerson, W. Klyne, and R. J. Swan, Tetrahedron,1966,22,1327; cf. W. F. Trager, C. M. Lee, and A. H. Beckett, ibid., 1967, 23, 365, 375.34 U. Weiss and T. Rull, Bull. SOC. china. France, 1965, 3707.s6 H. Wolf, Annalen, 1966, 695,98.s6 A. F. Beecham and A. McL. Mathieson, Tetrahedron Letters, 1966, 3139.37 R. S. Cahn, C. K. Ingold, and V. Prelog, Angew. C M . , 1966, 78, 413.38 A. Moscowitz, E. Charney, U. We&, and H. Ziffer, J.AM. Chem. SOC., 1961,83, 4661.39 G. Snatzke, E. Sz. Kovats, and G. Ohloff, Tetrahedron Letters, 1966, 4551.40 M. Legrand and R. Viennet, Compt. rend., 1966, 262C, 1290; A. Y O ~ V and Y.Mazur, Tetrahedron, 1966, 22, 1317; C. R. Enzell and S. R. Wallis, Tetrahedron Letters,1966, 243.4 1 H. E. Smith and R. Records, Tetrahedron, 1966, 22, 813.43 G. C. Barrett, J . Chm. SOC. (C), 1966, 1771.4 3 W. Scott-Briggs and C. Djerassi, Tetrahedron, 1965, 21, 3455SCOPES : OPTICAL ROTATORY DISPERSION 269amplitude of the sulphide Cotton effects to the disposition of the moleculearound the episulphide ring.44Carboxyl Chromophore.-The carboxyl chromophore, rigidified as inlactones, has been intensively studied45-47 over a wide range of stereo-chemical types.Two different attempts have been made to correlate theobserved sign and magnitude of the lactone Cotton effect with the geometryof the asymmetric environment of the chromophore. Snatzke's approach 45stresses the difference between the two oxygen atoms (formally doubly andsingly bonded), while the carboxyl sector rule 47 stresses the similaritybetween the two oxygen atoms and treats the carboxyl group, as a Grstapproximation, as syrrimetric about the plane bisecting the OCO angle. Thesector rule has been applied to asymmetric esters, particularly steroidacetates. 48 The conformation 49 and absolute configuration 5O of variousacids has also been studied by 0.r.d.Considerable interest has been shown in the 0.r.d. and c.d. of smallpeptides 51-54 and related compounds,55 which contain the carboxyl chromo-phore as both free acid and as amide and which may be considered as non-helical model systems for larger peptides, polyamino-acids and proteins.Small peptides have been studied in which a single asymmetric leucine 5l orproline 5 2 residue is inserted in a chain of glycine residues, and the effect ofthe terminal groups has been particularly studied in dipeptide~.~~ The 0.r.d.of all possible diastereoisomeric tri- and tetra-peptides of alanine and serinehas been used to deduce contributions for each individual chromophore in them0lecule.5~Carbohydrates,-Most oligosaccharides give plain 0.r.d.curves down to200 mp but Cotton effects have been reported for a number of acylatedamino-sugars.44 K.Kuriyama, T. Komeno, and K. Takeda, Tetrahedron, 1966, 22, 1039.45 G. Snatzke, H. Ripperger, C. Horstmami, and K. Schreiber, Tetrahedron, 1966,46 H. Wolf, Tetrahedron Letters, 1966, 5151.4 7 J. P. Jennings, W. Klyne, and P. M. Scopes, J. Chem. SOC., 1965, 7211, 7229;W. Klyne, P. M. Scopes, and A. Williams, ibid., p. 7237; C . G. do Grazia, W. Klyne,P. M. Scopes, D. R. Sparrow, and W. B. Whalloy, J . Chem. SOC. (C), 1966, 896.48 J. P. Jennings, W. Klyne, W. P. Mose, and P. M. Scopes, Chem. Comm., 1966,553.48 W. Gaffield, A. G. Waiss, and J. Corse, J . Chem. SOC. (C), 1966, 1885.50 J. C. Craig, S. K. Roy, R. G. Powell, and C. R. Smith, J. Org. Chem., 1965, 30,4342; J. C. Craig, R. J. Dummel, E. Kun, and S. K. Roy, Biochemistry, 1965, 4, 2547;H. Yonehara and N.Otake, Tetrahedron Letters, 1966, 3785.61 A. F. Beecham, Tetrahedron Letters, 1965, 4757; ibid., 1966, 957.6 2 P. J. Oriel and E. R. Blout, J . Arner. Chem. SOC., 1966, 88, 2041.63 M. Legrand and R. Viennet, Compt. rend., 1966, 262C, 943.64 J. Beacham, V. T. Ivanov, P. M. Scopes, and D. R. Sparrow, J . Chem. SOC. ( C ) ,6 5 D. Balasubramanian and D. B. Wetlaufer, J . Amer. Chem. SOC., 1966, 88, 3449.s6 S. Beychok and E. A. Kabat, Biochemistry, 1965, 4, 2565.22, 3103.1966, 14492. Part (iv). Mass SpectroscopyBy John M. Wilson(Department of Chemistry, University of Munchester, Manchester, 13)General Methods of Interpretation.-The most interesting advance in maasspectrometry in the past year has been the rapid development of automaticmethods for the interpretation of ~pectra.l-~ Three groups have producedcomputer programs for the structure determination of peptides from theirmass spectra.The most versatile of these will distinguish between linear,cyclic, and depsi-peptides. In an attempt to develop programs of a moregeneral appli~ability,~ the nomenclature system of ‘‘ ion types ” has beenpr~posed.~ This system classifies an ion according to its hetero-atom contentand degree of saturation. Another scheme of fragmentation types has beenproposed. tiThe argument about the nature of the fragmentation processes and theimportance of charge localisation continues. Proponents of various viewsemphasise the importance of product stability 7 and of the “odd or evenelectron ” status of ions.8 Ionisation-potential measurements on somesubstitutcd ureas and thioureas suggest that the charge is localised in thesemolecidar ions, if only at energies close to the ionisation threshold.Therehave been two important attempts to provide new methods for the criticalstudy of fragmentation processes : the examination of substituent effects loand the identification of ions by observation of the metastable transitionsthey can undergo.ll The former method has been widely used in the study ofionisation and appearance potentials,12 but a recent study on the fragmenta-tion of substituted methyl benzoate esters shows that the abundance of the(C0,CH3) + ion can be correlated with substituent constants, whereas theabundance of the fragment ions containing the substituents cannot be sorelated.l3There has been an increase in the study of metastable ions, partly due toK.Biemann, C. Cone, B. R. Webster, and G. P. Arsenault, J . A w . c’hm. SOC.,2 M. Senn, R. Venkataraghavan, and F. W. McLafferty, J. Amw. Chem. Soo., 1966,3 M. Barber, P. Powers, M. J. Wallington, and W. A. Wolstenholme, Nature, 1960,4 K. Biemann and JV. J. RlcMurray, Tetrahedron Letters, 1965, 647.6 K. Bismann, W. J. McMurray, and P. IT. Fonnessey, Tetrahedron Letters, 1966,6 P. Longevialle, Bull. SOC. chim. France, 1966, 437.7 G. Spiteller and M. Spitellsr-Friedmann, A n n a h , 1965, 890, 1.8 F. W. McLafferty, Chem. Comm., 1966, 78.Q M. Baldwin, A. Kirkien-Konasiewicz, A. G. Loudon, A.Maccoll, and D. Smith,1966,88, 5598.88, 5593.184.3997.Chern. Conam., 196G, 574.10 F. W. McLafferty and M. M. Burssy, J . Amer. Chm. SOC., 1966, 88, 529.11 T. W. Shannon and F. W. McLafferty, J. Amer. C h . SOC., 1966, 88, 5021.12 A. G. Harrison, P. Kebarle, and F. P. Lossing, J . Amer. Chem. SOC., 1961, 83,777; J. M. Tait, T. W. Shannon, and A. G. Harrison, ibid., 1962, 84, 4 ; R. W. Tdt,R. H. Martin, and F. W. Lampe, ibid., 1965, 87, 2490.13 J. L. Mateos and C. PBrez G., Bol. Inst. Quim. Univ. Nao. Auton. Mex., 1966,17, 202WILSON: MASS SPECTROSCOPY 271the increased sensitivity of detection of transitions in the &st field-freeregion of a double-focusing mass spectrometer.14 This effect has been used toproduce evidence for the participation of substituted tropylium ions in thedecomposition of substituted toluenes.15 The other major application ofmetastable ions has been in the study of decompositions which involverelease of kinetic energ~.14(~), 1 6 The value of the kinetic energy release forthe processC6HaS+ --+ C,H,+ + CH,+is used as evidence for an acyclic structure for doubly charged benzene ions.''Consecutive metastable transitions for the processC,H,+ + C,H,+ + C,R,+have been found using both field-free regions of a double-focusing massspectrometer.18 Computer programs have been described for the analysisof metastable ions lga, and of spectra involving elements with complicatedisotope patterns .mbIon Sowces.-T'here has been a resurgence of interest in spectra obtainedusing modified ion-sources.The simplest method, that of using a con-ventional electron-impact source a t temperatures lower than normal, has theeffect of increasing the abundance of the molecular ion and producing aspectrum with more specific fragmentation than is found a t higher tem-peratures.20 This effect is most pronounced for diphatic compounds, buthas been applied to other systerns.2l The USB of a low-tempcrature sampleholder for direct inlet systems allows the measurement of pure electronimpact mass spectra of volatile, thermally unstable compounds.23 With theadvent of high-efficiency photoionisation sources it has become possible toobtain spectra a t room te~nperature.~~ With such a source the spectra ofcis- and trans-4-t-butyl-cyclohexanol showed much greater differences 24 thanwere found using electron impact a t higher temperatures.All these methodsattempt to improve the spectra because of better control over the energytransferred to the molecule being ionised. Two methods which go further inthis direction both involve the use of ion-molecule reactions. One group use8a tandem mass spectrometer in which the sample is bombarded with lowvelocity ArD+ i0ns.25 The energy transferred is mostly the recombinationenergy of the projectile ions. Using this method striking differences havel4 ( a ) K. Ryan, L. W. Sieck, and J. H. Futrell, J . Chem. Phys., 1965, 43, 1832;( b ) K. R. Jennings, ibid., p. 4176.1 5 K. R. Jennings and J. H. Futrell, J . Chem. Phys., 1966, 44,4315.l6 J.H. Beynon, R. A. Seunders, and A. E. Williams, 2. Naturforsch., 1965, 20s,180; T. W. Shannon, F. W. McLafferty, and C . R. McKinney, Chem. Cornm., 1966,478.l7 J. H. Beynon and A. E. Fontaine, Chem. Comm., 1966, 717.l s K . R. Jennings, Chem. Comm., 1966, 283.l9 (a) R. E. Rhodes, M. Barber, and R. L. Anderson, Analyt. C h . , 1966, 38, 48;N. R. Nancuso, S. Tsunakawa and K. Biernann, ibid., p. 1775; ( b ) J. I. Brauman,ibid., p. 607.2 0 G. Spiteller, M. Spiteller-Friedmann, and R. Houriet, Monatsh., 1966, 97, 121.22 W. F. Haddon, E. M. Chait, and F. W. McLafferty, Analyt. Chem., 196G, 88, 1968.2s C. E. Brion, Analyt. Client., 1965, 37, 1706; 1966, 38, 1941.24 C. E. Rrion and L. D. Hall, J . Amr. C h . Xoc., 1966, 88, 3661.4 6 L.Friedman, J. J. Leventhal, and T. F. Moran, J . Amer. Chem. SOC., 1966, 88,G. Spiteller and M. Spiteller-Friedmann, Angew. Chem., 1966, 78, 494.5060272 ORGANIC CHEMISTRYbeen found between the mass spectra of cyclopropane and propylene. Theother method uaed is chemical ionisation,26 in which the sample is introducedas an additive in a high pressure (ca. 1 Torr.) of methane in the ionisationchamber. The ions produced from methane under these conditions, CH,+,C2H5+, and C3H,+ react with the additive sample to give a characteristicspectrum. The principal processes are hydride abstraction [equation (A)]and proton addition [equation (B)] and most spectra show very abundantM-1 ions and M + 1 ions where the sample is a proton acceptor. The(4(B)fragmentation processes involved appear to be more specific than thosefound under normal electron-impact conditions, e.g., in the case of esters.*’A comparative study has been made of chemical ionisation and field ioni-sation spectra of some hydrocarbons.28Fragmentation Me&anisms.-There has been much active work in thisfield.In particular the work of the Stanford group has disconcerted thosewho have believed for some time that site-specific hydrogen-rearrangementprocesses are general. It has been shown, however, that the McLaffertyrearrangement equation (C) is site-specific for esters,29 ket~nes,~O oximes,MIRCK,R’ + CH,+ --+ RCHR‘ $- H, + CH,H+ R-0-R’ + CH,+ + R-0-R’ + CH,semicarba~ones,~~ and azornethine~,~~ although it may be suppressed in even-electron ions.34 In the double McLafferty rearrangement of ketones,=both hydrogen atoms are transferred specifically from y-carbon atomB.The isotope effect for such hydrogen transfers, defined as the ratio of deu-terium to protium transferred from a site where equal numbers of deuteriumand protium atoms are available, can vary from 0*50-0.98.s5In other systems the hydrogen-abstraction process is not so site-specifio.In the elimination of HC1 from l-chloropentane, 73% of the hydrogen isremoved from the 3-p0sition,~~ i.e., this is predominantly a 1,3-elimination, asopposed to the behaviour of aliphatic alcohols, which undergo a 1,4-elimina-26 M.S. B. Munson and F. H. Field, J . Amer. Chm. SOC., 1966, 88, 2621.27 M. S.B. Munson and F. H. Field, J . Amer. Chem. SOC., 1966, 88, 4337.28 H. D. Beckey, J. Arner. Chem. Xoc., 1966, 88, 5333.49 K. Biemann, “ Mass Spectrometry,” McGraw-Kill, New York, 1962, p. 121.*O H. Budzikiewicz, C, Fenselau, and C. Djerassi, Tetrahedron, 1966, 1391; E. Fritz,31 D. Goldsmit.h, D. Becher, S. Sample, and C. Djerassi, Tetrahedron, 1966, Sup-3a D. Becher, S. Sample, and C. Djerassi, Chem. Ber., 1966, 99, 2284.34 C. Djerassi, M. Fischer, and J. B. Thomson, Chem. Comm., 1966, 12.3s J. K. MacLeod and C. Djerassi, Tetrahedron Letters, 1966, 2183.36 A. M. Duffield, S. Sample, and C. Djerassi, Glwm. Comm., 1966, 193.H. Budzikiewicz, and C. Djerassi, Chem. Ber., 1966, 99, 35.plement No. 7, 145.M. Fischer and C. Djerassi, Chem. Ber., 1966, 99, 1541WILSON: MASS SPECTROSCOPY 273tion of water.37 In the mass spectra of n-butyl propionate and benzoate therearrangement products( 1) and (2) are formed largely by transfer of hydrogen,O-ti ( I ; R = Et 1R-CC(+ OH (2; R = Ph)from C-2 and C-3 of the butyl group, but C-1 and C-4 also contribute appre-ciably.38 In the mass spectra of dibutyl ether the formation of the ion (3)involves abstraction of hydrogen from all positions in the alkyl chain.39The behaviour of aliphatic amines is completely analog~us.~O A similar lackC,H90C4H, -+ C4H,0 = CH, + HO = CH,of specificity in hydrogen abstraction is found in the elimination of an" olefin " fragment from the molecular ion of n-butyl ~henylether.~~ Theion formed (4; R = H) is considered to be the phenol molecular ion, but the3.' + +(3)+-examination of substituent effects on the formation of this ion from variousaryl ethylethers suggests 42 that a skeletal rearrangement may be involved.Other studies on hydrogen rearrangement processes include work on esters,43steroidal ketone~,~4 and on the formation of CH,+ in the spectrum of 2-methoxyethanol.45The study of skeletal rearrangements has been the subject of muchresearch. A systematic study of some aromatic compounds did not yield anyalkyl migration analogous to the well-known processes involving hydrogen,46but the ion C,H,+ found in the spectrum of ethyl phenyl sulphide wasshown to be derived by elimination of sulphur from the ion (5) probablythrough the intermediate (6).Other sulphur compounda which showW. Benz and K. Biemann, J . Amer. Chmn. SOC., 1964,86,2375.C. Djerassi and C. Fenselau, J . Amer. C h . SOC., 1966, 87, 5756. ** C. Djerassi and C. Fenselau, J . A m . C h m . Soc., 1966, 87, 5747.40 C. Djerassi and C. Fenmlau, J . A m . Chem. SOC., 1966, 87, 5752.41 J. K. MacLeod and C. Djerassi, J. Amer. Chem. SOC., 1966, 88, 1840.4* F. W. McLafferty, M. M. Bursey, and S. M. Kimball, J . Amr. Chm. SOC., 1966,43 R. Ryhage and E. Stenhagen, Arkiv Kemi, 1965,23, 167.44 C. Djerassi and L. Tokes, J . A w . Chm. SOC., 1966, 88, 536.45 K. R. Way and M. E. Russell, J . Phys. Chm., 1965, 69, 4420.46 M. Fischer and C. Djerassi, C M . Bm., 1966, 9, 750.88, 5022274 ORGANIC CHEMISTRYskeletal rearrangements include thioethers,*' sulphoxides and sulphones,**di~ulphides,~~ and sulphonylhydrazones.5O In the mass spectra of sulphoxidesand sulphones some fragments are fermed after migration of an aryl groupfrom sulphur to oxygen, e.g., (7)+(8), a process analogous to the nitrogen tooxygen migration found in the mass spectra of aromatic nitro-compounds. 51The elimination of carbon dioxide from organic carbonates s2 has been welldocumented. In the case of methyl phenyl carbonate this must involve afour-centre transition state as in (9) because of the similarity between itsspectrum and that of anisole. The process is general for carbonates but notalways for thiocarbonates and thio~arbarnates.~~ One of the major fragmentions from N-methylphthalimide 54 and N-arylphthalimides 55 is formed byelimination of carbon dioxide from the molecular ion.The elimination ofstable neutral molecules has, of course, been recognised for some time to be apossible driving-force for many fragmentation processes. As anotherexample of this a wide variety of acyclic carbonyl compounds have beenfound to eliminate carbon monoxide from their molecular ions.56O = m (J?. (9)A process involving migration of an oxygen function is operathe in thedecomposition of the molecular ion of 4-hydroxy- and 4-methoxy-cyclo-hexanone.5' The suggested route is (10) +( 11) +( 12), which is analogous tothe methoxyl transfers found in the mass spectra of perrnethylated glyco-0- OR4 7 J. IT. Bowie, S . - 0 . Lawesson, J. 0. Madsen, G. Schroll, and D.R. Williams,J. Chcm. SOC. (B), 1966, 951; A. Tatematsu, S. Inoue, and T. Goto, Tetrahedron Letter8,1966, 4609.48 J. 0. Madsen, C. Nolde, S . - 0 . Lawesson, C. Schroll, J. H. Bowie, and D. H.Williams, Tetrahedron Letters, 1966, 4377.49 J. H. Bowie, S.-0. Lawesson, J. 0. Madsen, C. Nolde, G. Schroll, and D. H.Williams, J. Chem. SOC. (B), 1966, 946.6o A. Bhati, R. A. W. Johnstone, and B. J. Millard, J. Chem. SOC. (C), 1966, 358.61 S. Meyerson, I. Puskas, and E. K. Fields, J. Amer. Chem. Soc., 1966, 88, 4974.6a P. Brown and C. Djerassi, J. Amer. Chern. SOC., 1966, 88, 2469.69 J. B. Thornson, P. Brown, and C. Djerassi, J. Amer. Chew%. SOC., 1966, 88, 4049.64 R. A. W. Johnstone, B. J. Millard, and D. 8. Millington, Chem. C o r n . , 1966,600.66 J.L. Cotter and R. A. Dinehart, Chem. Comm., 1966, 809.66 J. I€. Bowie, R. G. Cooks, S.-0. Lawesson, P. Jakobsen, and G. Schroll, Chem.ti7 M. M. Green, D. S. Weinberg, and C. Djerassi, J . A m . Chem. Soc., 1966, 88,C m . , 1966, 539.3883WILSON: MASS SPECTROSCOPY 276sides.58 Alkoxy-migrations are also reported for glycidic esters,6Q theneutral species eliminated being HCOCO. or CO + CHO.involve migration of anaryl group followed by a predictable fragmenta.tion of the intermediateketone ion, e.g., (13). The metal atoms in organometallic compounds areRearrangement processes of aromatic epoxides+*Ph,C-COPhPh, ,O<' / Ph,c-c \Ph (13) Phoften involved in migration processes. The compound (14) producM anabundant ion C,,F,,Fe+ by a process in which an iron atom is eliminated.g1Analogous behaviour is found when the metal atom or the bridging groupsare changed and when carbonyl is replaced by nitrosyl.62 Other skeleta,lrearrangements have been found in the mass spectra of cyanoacetate~,~~dimethyl metals and methyl orthoformate,6* and benzyloxycarbonyl deri-vatives of peptides.65Bdiscellaneous.-The Russian group are continuing their work on the effectaof the stereochemistry of steroid systems on their mass spectra,.66 Thiscompletely empirical approach is highly successful.Other stereochemicaleffects observed involve steroid^,^' unsaturated alcohols,68 ferro~enes,~~norbornyl bromides,"J and t-butylcyclohexanols.2* Work continues on theuse of mass spectrometry to provide an insight into p,yrolytic proce~ses.~lAliphatic compounds which differ only in the position of a double bond oftena8K.Heyns and D. Muller, Tetrahedron, 1965, 65; N. K. Kochetkov and 0. 15.69 J. Baldas and Q. N. Porter, Chm. Comm., 1966, 571.6o H. Audier, J. F. Dupin, M. Fetizon, and Y. Hoppillard, T e t r W r o n LBttsrs,J. Lewis, A. R. Manning, J. R. Miller, and J. M. Wilson, J . Chem. SOC. (A), 1966,6 2 P. J. Preston and R. I. Reed, Chem. C o r n . , 1966, 51.63 J. H. Bowie, R. Grigg, S.-0. Lawesson, P. Madsen, G. Schroll, and D. H. Williams,64 M. J. Rix, A. J. C. Wakefield, and B. R. Webster, Chem. C o r n . , 1966, 748.66 R. T. Aplin, J. H. Jones, and B. Liberek, Chern. Comm., 1966, 794.e6 N. S. Wulfson, V. I. Zaretskii, V. L. Sadovskaya, A.V. Semenovaky, W. A. Smit.,and V. F. Kucherov, Tetrahedron, 1966, 22, 603; V. I. Zaretskii, N. S. Wulfson andV. L. Sadovskaya, Tetrahedron Letters, 1966, 3879; N. S. Wulfson, V. I. Zaretskii,V. L. Sadovskaye, S. N. Ananchenko, V. M. Rzhozhnikov and I. V. Torgov, Tetrahedron,1966, 22, 1885.e7 K. Egger, Monatsh., 1966, 9'9, 1290.68 H. E. Audier, H. Felkin, M. Fetizon, and W. Vetter, Bull. SOC. chim. France,69 H. Egger and H. Falk, Tetrahedron Letters, 1966, 437.7 0 D. C. de Jongh and S. R. Shrader, J . Amer. Chem. SOC., 1966, 88, 3881.71 R. F. C. Brown and R. K. Solly, Austral. J . Chem., 1966, 19, 1045; S. MeyeraonChizhov, ibid., p. 2029.1966, 2077.1663.J . A m r . Chem. SOC., 1966, 88, 1G99.1965, 3236.and E. K. Fields, J .Chem. SOC. (B), 1966, 1001276 ORGANIC CHEMISTRYgive almost indistinguishable mass spectra. Conversion to a suitable deri-vative is necessary for structure determination and so far the most convenientprocess involves oxidation to a diol and formation of an a~etonide,~~ whichundergoes specific fragmentation. This derivative is particularly suitable forthe g.1.c.-mass spectrometer combination.Other classes of compounds studied include p-ket~-esters,7~ semicarba-zones,74 nitrophenylhydra~ones,~5 methylcy~lopentadienes,~ coumt~rins,~~1,d-dicarbonyl cornpounds,78 and Schiff 79 Natural product massspectra are generally outside the scope of this article, but as a note of cautionthe spectrum of voacamine (1 8) 80 deserves mention. The heaviest ion is 14mass units above the molecular ion and is a result of intermolecular trans-methylation which takes place on heating prior to volatilisation of the sample.COzMeIJ.A. McCloskey and M. J. McClelland, J . Amer. Chem. Soc., 1965, 87, 5890.I* J. H. Bowie, S . - 0 . Lawesson, G. Schroll, and D. H. Williams, J . A m . Chem.7 4 D. Becher, S. Sample, and C. Djerassi, Chem. Ber., 1966, 99, 2284.76 A. G. Harrison, P. Haynes, S. McLean, and F. Meyer, J . Amer. Chern. Soc., 1965,7 7 R. A. W. Johnstone, B. J. Millard, F. M. Dean, and A. W. Hill, J . Chem. SOC. (C),78 S.-0. Lawesson, J. 0. Madsen, 0. Schroll, J. H. Bowie, R. Grigg, and D. H.E. Schumacher and R. Taubenest, Heh. Chim. Acta, 1966,49,1455.8o D. W. Thomas and K. Biemann, J . Amer. Chem.SOC., 1965, 87, 5447.SOC., 1E65, 87, 5742.C. Djerassi and S. D. Sample, Nature, 1965, 208, 1314.87, 5099.1966, 1712.Williams, Actu. Chem. Sculzd., 1966, 20, 11293. REACTION MECHANISMSPart (i). By B. C. Challis(Department of Chemiatry, St. Salvator's College, St. Andrews, Fife)Acidity Functions and Molecular Basicity.-Last year's Report emphasisedthe conviction that acidity function values depend on the indicator structure.Arnett and Mach 1 now h d that the order Ha (carbinol indicators) > HE'(aromatic olefins) > H,,"' (tertiary amines) > H i (primary amines) isgenerally followed, but differences between the various functions are notindependent of the solvent acid. However, the equilibrium protonation ofionic azobenzenes,2 aliphatic carboxylic acids,3 and substituted benzo-phenones? all follow the H,' function fairly closely.Also values of Hotfor aqueous sulphuric acid have been slightly modified again.sDifficulties prevail in understanding the causes of the different proto-nation behaviour of the various indicators. The almost linear dependenceof H,' on hydronium ion concentration for constant ionic-strength solutionsof HClO,,6 the observation that H,' values for H,SeO,, HClO,, and H,SO,are a single function of aH,0, and the negligible effect of the NH,+ group(compared to m e , + ) on the n.m.r. chemical-shifts of aromatic hydrogens inaidinium ions,8 have all been cited as evidence for the overwhelming im-portance of indicator ion hydration. This view has been questioned byArnett and co-w~rkers,~,~ however, because solvation entropies for primary,secondary, and tertiary amines in H,SO, (10-70y0) are nearly equal andrespond similarly to changes in acid concentrati~n.~ They also note that thecorrelation between the numerical magnitude of the acidity function and thephysical size of the indicator suggests that salt effects on the neutral indi-cator may be as important as those on its conjugate acid.l The protonationof benzophenones also indicates that salt effects on the neutral species can besignificant .4The breakdown of the acidity-function concept has led to a search both foralternative mechanistic criteria for acid-catalysed reactions and for solventsin which activity-coefficient behaviour is more predictable.Arnett andMach have championed the use of Setchenow equations and conclude thatthe sensitivity of protonation phenomena to substrate structure is greater insulphuric and perchloric acid than in hydrochloric acid. Also, Bunnett andOlsen lo have published full details of their linear free-energy (4) treatmentfor both equilibria loa and rates.lob This is intended to succeed the earlier wl E. M. Arnett and G. W. Mach, J . Amer. Chem. SOC., 1966, 88, 1177.R. L. Reeves, J . Amer. Chem. SOC., 1966, 88, 2240.S. Hoshino, H. Hosoya, and S. Nagakura, Canad. J . Chem., 1966, 44, 1961.T. G. Bonner and J. Phillips, J . Chem. SOC. ( B ) , 1966, 650.R. S. Ryabova, I. M. Medvetskaya, and M. I. Vinnik, Zhur. $2. Khirn., 1966,J. S. Day and P. A.H. Wyatt, J . Chem. SOC. ( B ) , 1966, 343; cf. B. C. Challis andD. H. McDaniel and L. K. Steinert, J . Amer. Chem. SOC., 1966, 88, 4826.G. Fraenkel and J. P. Kim, J . Asner. Chena. Soc., 1966, 88, 4203.E. M. Arnett and J. J. Burke, J . Amer. Chem. SOC., 1966, 88, 2340.40, 339.J. H. Ridd, J . Chem. SOC., 1962, 5208.lo (a) J. F. Bunnett and F. P. Olsen, Canad. J . Chem., 1966, 44, 1899; (a) ibid.,p. 1917278 ORGANIC CHEMISTICYand W* treatments and differs from the latter in that no a priori assumption ismade that substrates protonate in accordance with H,. Their approach,which bears some similarity to the Setchenow equation, seems useful fordetermining pR values directly from kinetic and equilibrium data loa and thecorrelation parameter (+) is also discussed in terms of hydration changes andthe function of water in reactions,lob along the lines developed earlier for wand w*. The development of acidity functions in sulpholane has progressedfurther; ions are poorly solvated in this solvent and different types of in-dicators may behave in a simpler fashion than in aqueous solutions.llThe heats of ionisation of weakly-basic amines jn 96.5% R,SO, show thatpK values determined by the '' Hammett overlap method " are probablyquite reliable l2 and some long-standing disagreements over the basicity ofseveral organic nitro-compounds,13u n i t r i l e ~ , l ~ ~ and acetone 13e have beenresolved by n.m.r.and distribution studies. The basicities of aliphaticalcohols and ethers have been confirmed by solubility measurements 14 andrecent reviews summarise current information on the base 15 and scid16strengths of aromatic hydrocarbons.Recent developments (until 1965) in acidity-function measurements inbasic solutions have been covered in excellent reviews l7 and further measure-ments of the H - functions have been reported.la Additional evidence to thatnoted last year shows the H - function for di-o-substituted phenol indicatorsdepends on the size of the o-substituents, suggesting that indicator anion sol-vation is important in basic so1utions.lsa The H2- function, based on theionisation of anionic acids [equation (l)]HA- + H+ + A3- (1)is numerically similar to the H - function in four aqueous solvent systems.l@These measurements show that aqueous dimethyl sulphoxide is a parti-cularly basic rnedium.19 Mechanistic implications of acidity function corre-lations in basic media have been discussed in connection with both base-catalysed elimination and proton-abstraction reactions.20Deuterium Isotope Eff ects.-These are discussed under three sub-headings, as for last year, and attention is drawn to two comprehensivereviews dealing with kinetic aSpects,2l one in particular with those relatingto E2 elimination reactions.21aPrimary isotope eflects.Further studies by Bell's group 22 on the ionisa-11 R. W. Alder, 0. R. Chalkey, andM. C. Whiting, Chem. Comm., 1966, 405.1s E. M. Arnett rand J. J. Burke, J . Amer. Chem. SOC., 1966, 88, 4309.13 ( a ) N. C. Deno, R. W. Gaugler, and T. Schulze, J .Org. Chem., 1966, 31, 1968;(b) N. C. Deno, C. W. Gaugler, and M. J. Wisotsky, ibid., p. 1967; (c) P. Salomaa andH. Kiesala, Acta C h m . Scand., 1966, 20, 902.14 N. C. Deno and J. 0. Turner, J . Org. Chem., 1966, 31, 1969.1 5 H.-H. Perkampus, Adu. Phys. Org. Chem., 1966, 4, 195.16 A. Streitwieser and J. H. Hammons, Prog. Phys. Org. Chem., 1965, 3, 41.1 7 K. Bowden, Chew". Rev., 1066,66,119; C . H. Rochester, Quart. Rev., 1966,20,511.1% (a) C. H. Rochester, J . C h m . SOC. ( B ) , 1966, 121; ( b ) D. Bethell and A. F.Cockerill, ibid., p, 913; ( c ) F. Terrier and R. Schaal, Compt. rend., 1966, 263, c, 476.10 K. Bowden, A. Buckley, and R. Stewart, J . Amr. Chem. Soc., 1966, 88, 947.20 D. Bethell and A. F. Cockerill, J . Chem.SOC. ( B ) , 1966, 920.21 ( a ) H. Simon and D. Palm, Alzgew. Chem., Internat. Edn., 1966,5,920; ( b ) W. H.z 2 R. P. Bell and D. 35. Goodall, Proc. Roy. SOC., 1966, A , 294, 273.Saunders, Surv. Prog. Chem., 1966, 3, 109CHALLIS : REACTION MECHANISMS 279tion ratio of pseudo-acids clearly demonstrate that symmetry of the trami-tion state is an important factor determining the magnitude of primaryeffects. The Xigure which plots log,,,(E~kD) against the difference in basestrengths of the reactants (ApK), shows a maximum for proton transferbetween bases of approximately equal strength (dpK = 0), as predictedearlier by Westheimer.23 The above results suggest that maximum primary-isotope effects will also accompany intramolecular proton-transfer reactionsand large kTi/kD ratios have been noted for the isomerisation of both5,8-dideuteriocyclo-octa-l,3,6-triene 24 and 1 -deuterio- 1 -methylindene, 25 be-lieved t o rearrange via transition states (1) and (2), respectively.Furtherconsideration of these rearrangements may elucidate other factors suspectedof reducing kH/kD ratios below their maximum value. A theoretical re-appraisal of some of these factors has been made recently.2s A resultdifficult to understand in view of these findings is the low kinetic ratio(kH/kD = 1.77 at 27 ") reported for proton exchange between 2,6,2',6'-tetra-t-butylindophenol and its phenoxy-radical and the reaction is probably morecomplex than superficial considerations suggest. 27 Substrate-dependentprimary-isotope effects have been recorded for E2 elimination in 2,2-diphenyIethylbenzenesulphonate,28 for proton abstraction from aliphaticketones by t-butoxy-radicals 29 and in the gas-phase McLafferty rearrange-ment; 30 the mechanistic implications are discussed in each case.In accord with earlier measurements,31 Bell and Goodall 22 also report thatproton abstraction from 2-nitropropane by 2,6-lutidine exhibits an abnor-mally large primary-effect (ICH/kD 21 20) and appreciable proton tunnelling istherefore suspected.Tunnelling has also been cited in the acid cleavage ofallylmercuric iodide 32 and in the E2 elimination of 9-bromo-9,9'-bifluor-e n ~ l ; ~ ~ however, tunnelling is not important in the E2 elimination of 2,2-diphenylethyl benzenesulphonate,34 as was suggested by earlier work with 2-phenylpropyl bromide.35Several recent studies have been concerned with hydrogen abstraction by23 F.H. Westheimer, Chem. Rev., 1961, 61, 265.24 H. Kloosterzoil and A. P. Ter Borg, Rec. Trav. chim., 1965, 84, 1305.2 5 L. Ohlsson, I. Wallmark and G. Bergson, Acta Chem. Scand., 1966, 20, 760;cf. G. Bergson and A.-M. Weidler, ibid., 1964, 18, 1498.26 W. H. Saunders, Chern. and Ind., 1966, 663.2 7 R. W. Ifieilick and S. I. Weissman, J. Amer. Chem. Soc., 1966, 88, 3646.28 A. V. Willi, Helv. Chirn. Acta, 1966, 49, 1725.2s K. Schwetlick and R. Spitz, J. prakt. Chem., 1965, 30, 218.30 J. K. Macleod and C. Djerassi, Tetrahedron Letters, 1966, 2183.ar E. S. Lewis and J. D. Allen, J. Amer. Chem. Soc., 1964, 88, 2022; E.S. Lewis32 M. M. Kreevoy and P. J. Steinwald, J. Amer. Chern. Soc., 1966, 88, 124.33 D. Bethel1 and A. F. Cockerill, J. Chem. SOC. ( B ) , 1966, 917.3 4 A. V. Willi, J. Phys. Chem., 1966, 70, 2705.3 5 V. J. Shiner and M. L. Smith, J. Amer. Chm. SOC., 1961, 83, 593.and L. Funderburk, ibid., p. 2531280 ORGANIC CHEMISTRYmethyl radicals and generally the isotopic rate ratios are those expected fromzero-point energy difference^.^^ An unexpected result, however, is thatabstraction from [ZHB]isobutane at 310" is normal for methyl radicals(k&-, = 10.4) but not for methylene radicals kH/kD = 0.84).37 The reasonfor this difference is not clear.Secondary isotope effects. An interesting development is the forcefuladvocation of Brown and his co-workers 38 that most secondary effects arisefrom differences in non-bonded rather than electronic (i.e., inductive andhyperconjugative) interactions.The isotope effect can then be understood interms of smaller steric requirements for the deuteriated species, along thelines suggested earlier by Bartell. 3B Thornton,40 however, has emphasisedthat steric and inductive interpretations are not fundamentally different.The conclusions of Brown and his co-workers come from studies of the reac-tion of methylpyridines with alkylhalides, in which a rate increase ondeuteriation of the %methyl substituent is ascribed to reduced sterichindrance, whereas the negligible effects accompanying deuteriation ofeither 3- or 4-methyl groups indicates that neither hyperconjugative norinductive electron release can be important (v.Table).380 Similar Itrendsare found in the heats of reaction of methyl pyridines with BF,, but not withKinetic isotope effects for reaction of methylpyridines and theirdeuteriomethyl analogues with CH,I at 25"Pyridine k H P D4-Me 1 .oo 13 -Me 1.0092 -Me 1 *0302,6-Me, 1.095the smaller BH3 reagent.38b Independent evidence from the preparation ofoptically pure sulphinate esters also shows that CH, is effectively larger thanCD3,41 and the importance of steric, as opposed to inductive, differences hasbeen stressed in connection with E l eliminations 42 and the stability of olefin-iodine c~mplexes.~~~ 38b N-Deuteriation raises the activation energy(AEA = 3.2 kcal./mole) for the inversion of 2,2',3,3'-tetrarnethylaziridine 44and this, too, may partly arise from a reduction of non-bonded interactions inthe ground state.Relief of non-bonded interactions accompanying the change from sp3 to8p2 hybridisation can also be used to explain the rate reduction arising from36 R.Shaw and J. C. J. Thynne, Trans. Paraday SOC., 1966, 62, 104; P. Gray andA. Jones, ibid., 1965, 61, 2161; ibid., 1966, 62, 112.37 M. L. Halberstadt and 5. R. McNesby, J . Chem. Phys., 1966, #, 1666.88 (a) H. C. Brown and Gr. J. McDonald, J. Amer. Chem. SOL, 1966, 88, 2514;(a) H. C. Brown, M. E. Azzaro, J. G. Koelling, and G. J. McDonald, ibid., p. 2520.XI L. S. Bartell, J . Arner. Chem. SOC., 1961, 88, 3567.4O E. R. Thornton, Ann.Rev. Phys. Chm., 1966, 17, 349.4 1 M. M. Green, M. Axelrod, and K. &low, J . Amer. Chem. SOC., 1966, a, 86L;A. Horeau, A. Nouaille, and K. Mislow, {bid., 1965,87, 4957.42 G. H. Cooper and J. McKenna, Chem. Comm., 1966, 734.43 R. J. Cvetanovic, F. J. Duncan, W. E. Falconer, and W. A. Saunders, J . Arne?.Chem. Soc., 1966, 88, 1602; cf. R. J. Cvetanovic, F. J. Duncan, W. E. Falconer, andR. S. Irwin, ibid., 1965, 87, 1827.44 T. J. Bardos, C. Szantay, and C. K. Navada, J . Amer. Chem. Soc., 1965,87, 5796CHALLIS : REACTION MECHANISMS 281a-deuteriation in limiting ( XN1) solvolyses 45 and another temperaturedependent isotope effect for such reactions is reported for cyclopropylcar-binyl chloride.46 The same arguments predict a rate increase (kE/k~ < 1)when the hybridisation changes from qP to spa, and such have been ob-served in radical addition to cyclic dienes 47 and in the polymerisation of~tyrene.~8 The absence of a similar effect in the hydration of styrene mayindicate a more complex mechanism than that proposed.49 Other studies thisyear include the effect of a-deuteriation on dipole moments 6o and &2solvolysis of methyl iodide,51 and a redetermination of the acidity of tri-deuterioacetic acid.52Secondary /?-deuterium effects in the thermal decomposition of azobis-or-phenylethane 530 and a-phenylperpropionate (kH/kD 21 1-01 per D atom)have been regarded as evidence for hyperconjugative stabilisation of thea-phenethyl radical.This retardation is about one-fourth of the corres-ponding effect in the a-phenethylcarbonium ion, suggesting that the phenylgroup dominates stabilisation of the radical.s3a The observed kR/kD ratio,however, would not be inconsistent with a steric interpretation and anopposite effect (kH/kD = 0.99 per D atom) results from an indirect measure-ment in connection with the polymerisation of styrene.48Different potential barriers for the rotation of CH, and CD, groups weresuggested some time ago to account for temperature independent p-deuterium-isotope effe~ts.5~ A similar effect may explain the preference of dideuterio-methylene for the exo-position of methylene-cyclopropane in the pyrolysis of(3), arising from the larger preponderal effect of the CD, rotation (k, < kH)into the ring configuration.55A useful summary of recent investigations 56 and a critical review of thetheoretical interpretations of secondary isotope effects 40 were published in1966.46 A.Streitwieser, “ Solvolytic Displacement Reactions,” McGraw-Hill, New York,1962, p. 172.4 6 C. Y. Wu and R. E. Robertson, Chem. and Ind., 1966, 195.4 7 A. Ekstrom and J. L. Garnett, Chem. Comm., 1966, 290.48 W. A. Pryor, R. W. Henderson, R. A. Patsiga, and N. Carroll, J . Amer. Chem.49 W. M. Schubert and B. L a m , J . Anzer. Chem. SOC., 1966, 88, 120.bo V. W. Laurie and J. S. Muenter, J . Amer. Chem. SOC., 1966, 88, 2883.61 A. V. Willi, Canad. J. Chem., 1966, 44, 1889.62 M. Paabo, R. G. Bates, and R. A. Robinson, J . Phys. Chem., 1966,70,540, 2073.aa (a) 8. Seltzer and E.J. Hamilton, J . Amer. Chem. SOC., 1966, 88, 3775; ( b ) T. W.64 K. T. Leffek, R. E. Robertson, and 5. Sugamori, Canad. J . Chem., 1961, 39,66 R. J. Crawford and D. M. Cameron, J . Anzer. Chem. Soc., 1960, 88, 2589.66 P. Laszlo and Z. Welvart, Bdl. SOC. chim. France, 1966, 2412.SOC., 1966, 88, 1199.Koenig and W. D. Brewer, Tetrahedron Letters, 1965, 2773.1989282 ORQANIC CHEMISTRYSolvent isotope eflects. Two recent reviews also deal with solvent isotope-effects 66, 40 and, in one, Thornton 40 refines the case for the importance oftransition-state as opposed to initial-state solvation in solvolysis reactions.Measurements of ion partial molar volumes s7a and heats of solution 573 alsobear on this problem and tentatively support the importance of initial statesolvation. Although the conductance of ions in H20 and D20 has beenrationalised on the basis of Swain and Bader’s 68 treatment of solventisot~pe-effects,~g investigations of both heats of dilution 6o and solution 67bof alkali-metal salts indicate their theory requires modification, and this, inturn, may resolve the differences over solvent isotope-effects in solvolysisreactions. Also pertinent to this question are the many recent studies show-ing that D20 has more structure than H20 (or, as far as an organic chemist isconcerned, that D-bonds are stronger than H-bonds),6I and the measurementof heat capacities of activation for solvolysis in H20.62 The Swain and Badertreatment 58 has also been extended to H20-T20 mixtures.63Recent fears that isotopic partition function ratios do not accord with therule of the geometric mean have been substantiated by Friedman andShiner’s 6 4 experimental measurement of the equilibrium constant (R = 3.76)for the fractionation of hydrogen isotopes in H20 and D20 [equation (2))This means that changes will be necessary in the theory and numericalcalculations for reactions in H20-D20 mixtures. Other studies on the dis-sociation of periodic acid indicate that transfer effects for species from H,Oto D20 do not always cancel, as most current theories ass~me,~5Details of Gold and Kessick’s 66 study of isobutene hydration in H20 andD20 have now appeared and the data have been elegantly used to codinn themechanism of hydrogen exchange between t-butyl alcohol and the solvent.67Both the hydration of isobutane and styrene 40 appear to involve slowproton transfer from H30+.Solvent isotope-effects have proved useful inelucidating the hydrolysis mechanism for imidazolium ions,68 amide~,~gIT (a) R. E. Robertson, S. E. Sugarmori, R. Tse, and C. Y. Wu, Canad. J . Chm.,1966, 44, 487; (6) D. H. Davies and G. C. Benaon, ibid., 1965, 43, 3100.68 C. G. Swain and R. F. W. Bader, Tetrahedron, 1960,10,182; C. G. Swain, R. F. W.Bader, and E. R. Thornton, ibid., p. 200.69 C. G. Swain and D. F. Evans, J . Amer. @hem. SOC., 1966,88, 383.60 C. Y. W u and H. L. Friedman, J . Phys. Chem., 1966, 70, 166.O1 R. L. Kay and D. F. Evans, J . Phys. Chem., 1966, 70,2336; E . E. Schrier, R. L.Loewinger, and A.H. Diamond, ibid., p. 686; M. R. Thomas, H. A. Scheraga, andE. E. Schrier, ibid., 1965, 69, 3722.82 A. Queen and R. E. Robertson, J . Anzer. Chem. Soc., 1966, 88, 1363; C. Y. Wuand R. E. Robertson, ibid., p. 2666.G3 M. Salomon, Canad. J . Chem., 1966, 44, 689.64 L. Friedman and V. J. Shiner, J . Chem. Phys., 1966, 44, 4639.65 P. Salomas and A. Vesala, Acta @hem. Scand., 1966, 20, 1414.V. Gold and M. A. Kessick, J . Chem. SOC., 1965,6718; B. Capon and C. W. Ress,V. Gold and L. C. Gruen, J . Chem. SOC. ( B ) , 1966, 600.68 J. A. Fee and T. H. Fife, J . Org. Chem., 1966, 31,2343.eS R. L. Schowen, H. Jayamman, L. Kershner, and G. W. Zuorick. J . Amr. Chcm.Ann. Reports, 1964, 61, 272.Soc., 1966, 88,4008CHALLIS : REACTION MECHANISMS 283tetrabenzyl pyropho~phates,~O and diox0lones,7~ and in establishing intra-molecular hydrogen-bonding in dicarboxylicLinear Free Energy Relationship.-The topic has not been specificallyreported in previous years.Currently there is considerable interest in thedevelopment of quantitative relationships in organic chemistry, and a newone, based on the coherence between carbonium-ion stabilities and theirselectivity, is claimed to detect the intermediate formation of ion-pairs insolvolysis reactions.73 The utility of iso-kinetic plots has also been dis-cussed further.74 Most attention, however, is focused on Hammett andTaft-Ingold equations, and the related interpretation of substituent effects.As excellent reviews dealing with all aspects of these equations have beenpublished,75 only recent developments will be considered.Aromatic substitwnt efects.The origin of inductive effects continues to bestrongly debated. Some of the conclusions drawn from 19F n.m.r. data forsubstituted benzenes have been seriously questioned by Dewar and Mar-chand,Y6 who now find that 3’-substituents in 4-fluorobiphenyls (4) producelarger 19F chemical-shifts than 3-substituents in fluorobenzene (5). Whenconsidered with comparable data for substituted terphenyls (6), the resultsmggest that the Taft 77 division of substituent effects into a-inductive (aI)and resonance (aa) contributions is incorrect, but they support the two-parameter treatment of Dewar and Grisdale 78 based on resonance and direct-field effects.It is also stressed that a more refbed treatment must include\ \ \ 8” Ox F 8”at least the resonance-field and n-inductive interactions as well.76 Partialsupport for these conclusions comes from the effect of 2’-, 3‘- a,nd 4’-sub-stituents on the dissociation of biphenyl-4-carboxylic acids and 4-ammoniumions, which cannot be easily rationalised on the basis of classical a-inductiveand resonance effects. It is interesting to note, however, that Dewar and70 R. Blakeley, F. Kerst, and F. H. Westheher, J . Amer. Chern. Soc., 1966,88,112.71 P. Salomaa, Ada Chem. Scancl., 1966, 20, 1263.7 a E. Eyring and J. L. Haslam, J . Phys. Chem., 1966, 70, 293; M. H. Miles, E. M.Eyring, W. E. Epstein, and M. T. Anderson, ibid., p. 3490.7 s R. A. Sneen, J.V. Carter, and P. S. Kay, J . Amer. Chem. Soc., 1966, 88, 2595.74 J. E. Leffler, J . Org. Chem., 1966, 31, 533.7 5 S. Ehrenson, Prog. Phys. Org. Chem., 1965,3,195; C. D. Ritchie and W. F. Sager,ibid., p. 323; H. H. Jaff6 and H. L. Jones, Adu. Heterocyclic Chem., 1964, 3, 209.76 M. J. S. Dewar and A. P. Marchand, J . Amer. Chem. SOC., 1966, 88, 3318.p7 R. W. Taft, J . Phys. Chem., 1960, 64, 1805.78 M. J. S . Dewar and P. J. Grisdale, J . Amer. Chem. SOC., 1962, 84, 3548.284 ORQANIC CHEMISTRYGrisdale CT,',~ and constants do not produce a significantly better corre-lation than Hammett cr parameters, and steric interaction with the n-elec-trons rather than direct-field effects are invoked to account for the generalbase-strengthening by 2'-substit~ents.7~The nature of inductive effects has been discussed further by Dewar andMarchand, who conclude that CF, substituents operate mainly by direct-field rather than n-inductive interaction, and powerful electron withdrawalby the C(CN), substituent (a, = 1.00) has been explained similarly.81However, the correspondence of both lQI? (ref.82) and 13C chemical-shifts e3for several substituted benzenes with n-electron densities calculated by con-sideration of only n-inductive interactions suggests the situation is notcompletely understood.Other recent studies of mbstituent effects include several involvingl9l? n.m.r. measurements in pentafl~orobenzenes.8~ A relationship betweenthe chemical-shift of p-fluorine and the o-fluorine-p-fluorine coupling con-stant is claimed to distinguish between n-electron donation and withdrawalby substituents in pentafluorophenylphosphines 84d and similar deductionshave been made from 1QF chemical-shifts in metal-organic c0mpounds.8~Some of these conclusions may need revision in the light of Dewar andMarchand's 76 findings.The 15N chemical-shifts for p-substituted nitro-benzenes correlate with corresponding l3C and 1QF data.86The separation of substituent parameters into their resonance (ox) and Q-inductive ( aI) components [equations (3) and (4)] continues to attractsupport. The general concordancy between oRo parameters derived from theintensities of aromatic C-H stretching vibrations with those from 1QF and13C n.m.r. data,87 and the observation that aR0 values are directly related todeviations from the plot of a, against op for substituted benzoic acids,*8have both been regarded as validation of Taft's 77 two parameter treatment.However, other workers have correlated aromatic G-H stretching vibrationintensities with aI parameters.89 The separation of substituent effects has7 9 D.J. Byron, G. W. Gray, and R. C. Wilson, J . Chem. SOC. (C), 1966, 831, 837.81 J. K. Williams, E. L. Martin, and W. A. Sheppard, J. Org. Chem., 1966, 31, 919.a2 G. L. Caldow, Mol. Phyt?., 1966, 11, 71.83 D. T. Clark, Chem. Comm., 1966, 390.84 ( a ) J. Homer and L. F. Thomas, J . Chem. SOC. ( B ) , 1966, 141; ( 5 ) A. Peake andL. F. Thomas, Chem. Comm., 1966, 629; (c) R. J. Abraham, D. B. MacDonald andE.S. Pepper, ibid., p. 542; (d) M. G. Hogben, R. S. Gray, and W. A. G. Graham, J . Amer.Chem. SOC., 1966, 88, 3458.85 0. W. Parshall, J . Amer. Chem. SOC., 1966,88,704; R. W. Taft and J. W. Rakshya,ibid., 1965, 87, 4387.a6 D. T. Clark and J. D. Roberts, J . Amer. Chem. Soc., 1966, 88, 745.137 R. T. C. Brownlee, A. R. Katritzky, and R. D. Topsom, J . Amer. Chem. Soc.,1966, 88, 1413.8 8 R. Pollett and R. Van Pouke, Tetrahedron Letters, 1965, 4741.89 E. D. Schmid, V. Hoffman, R. Joeckle, and F. Lagenbucher, Spectrochim. Ado,1966, 22, 1615; E. D. Schmid and F. Lagenbucher, ibid., p. 1621; E. D. Schmid andV. Hoffman, ibid., p. 1633; E. D. Schmid and R. Joeckle, ibid., p. 1645; E. D. Schmid,ibid., p. 1659.M. J. S. Dewar and A. P. Marchand, J . Amer.Chem. SOC., 1966, 88, 354CHALLIS : REACTION MECHANISMS 285been studied further by Exner 90 and the results support a two-parametertreatment, although its interpretation is questioned. Yukawa and Tsuno 91have also discussed their extended Hammett relationship in terms of reso-nance and inductive interactions.There is more evidence for the " saturation " of n-resonance stabilisationeffects, this time in connection with both electron withdrawal from thetrityl anion 92 and electron-donation to methyl cations.g3 This leads.McKeever and Taft 92 to conclude that the formulation of a set of resonance-enhanced substituent parameters (G+, 0-, etc.) of universal applicability willnever be possible.Substituent parameters have been measured for several phosphorus-containing groups 94 and there is evidence that conjugation in arylphosphinesinvolves 3d orbitals,g5 as reported recently for silicon-96 and sulphur-con-taking 97 substituents. A similar conclusion has been reached from studieswith phosphonium ylides, although in this case substituents other thancarbanions appear to interact with the phosphorus only by 0- and n-inductivemechanisms and not by resonance.98 Dipole-moment measurements suggestthat the direction of the CH, inductive effect may depend on its attachment tosaturated and unsaturated residues.50 Other recent work has been con-cerned with ortho-effects in the ionisation of anilines 99 and phenols; theacid-weakening by o-CH, groups in phenols is now attributed to sterichindrance to solvation of the phenolate ion rather than inductive electronrelease.looThe Harnmett rektionship. The usual assumption made in applying theHammett equation is that p values are independent of the substituentsposition. Recent hydrolysis studies of 6- and 7-substituted methyl 2-naphthoates now show this assumption is incorrect (as anticipated by Hine lolsome time ago), although pm = pp for benzene derivatives so long as resonanceinteractions between the aromatic system and the reacting side-chain do notchange during the reaction. It is also apparent that p values for reactionsin substituted benzenes are poor approximations to p values for the samereactions in other aromatic systems.lO2The applicability of the Hammett relationship to rates and equilibria in0.Exner, Coll. Czech. Chem. Comm., 1966, 31, 65.91 Y. Yukawa and Y. Tsuno, Mem. Inst. Sci. Ind. Res., Osaka Univ., 1966, 23,ga L. D. McKeever and R. W. Taft, J . Amer. Chm. Soc., 1966, 88,4544.g3 R. H. Martin, F. W. Lampe, and R. W. Taft, J . Amer. Chem. SOC., 1966, 88,g4 H. L. Retcofsky and C. E. Griffin, Tetrahedron Letters, 1966, 1975; G. P. Schie-g5 J. E. Bissey and H. Goldwhite, Tetrahedron Letters, 1966, 3247.g6 L. Goodman, A. H. Kohnstam, and L. H. Sommer, J . Amer. Chem. Soc., 1965,97 L. Goodman and R. W. Taft, J . Amer. Chem. SOC., 1965, 87, 4385.g* A. W. Johnson, S. Y. Lee, R. A. Swor, and L. D. Royer, J . Amer. Chem. SOC.,gg J. 0. Schreck, C. K. Hancock, and R. M. Hedges, J . Org. Chem., 1965, 30, 3504.loo C.L. de Ligny, H. J. M. Kreutzer, and G. F. Visserman, Rec. Trav. chim., 1966,lol J. Hine, J . Amer. Chem. SOC., 1959, 81, 1126.lo2 P. R. Wells and W. Adcock, Austral. J . Chem., 1966, 19, 221.71; Y. Yukawa and Y. Tsuno, J . Chem. SOC. Japan, 1965, 86, 873.1353.menz, Angew. Chem., Internat. Edn., 1966, 5, 731.87, 1012.1966, 88, 1953.85, 5286 OBQANIC CHEMISTRYfree-radical reactions has never been clear and Walter lo3 has now developeda structural criterion for predicting the nature of substituent effects in stablefree-radicals. This criterion has been justified theoreti~ally,1~~~ and thehyperfine-splitting constants of radical anions derived from l-phenyl- 13-propanediones are in accord with its predictions.lo4 Ion intensities in themass spectra of substituted benzo- and aceto-phenones correlate with cr-constants.lo5 It is therefore suggested that linear free-energy relationshipswill be as useful for elucidating mechanism and predicting spectra in gas-phase unimolecular ion-decompositions as in solution reactions,105u and thetechnique is applied successfully to prove the existence of two pathways forthe formation of C6H,+ and C,H,+ in the decomposition of benzo- andbutyro-phenones. 105bTwo recent reviews have summarised organic acid and base strengths andthe application of both the Hammett and Ingold-Taft relationships to theprediction of dissociation constants is discussed in detail. lo6 Charton 107has continued his extensive analysis of substi tuent effects in Diels-Alderreactions,107u on n-donors in charge-transfer complexes,107b and on theionisation constants of quinolines, i~oquinolines~~07~ imidazoles, l*Vd and1,lO-phenanthrolines all these results are fitted to modified forms of theHammett equation consisting of linear combinations of substituent para-meters and analysed in terms of special interactions occurring in thesesystems.Another interesting investigation concerns the use of cr+ parameters todifferentiate between SNl and mixed (SN1 and 5,2) mechanisms of solvolysisof benzhydryl thiocyanates.lo8 A linear combination of cr and cr- valueg,directly analogous to that developed by Yukawa and Tsuno lo9 for aromaticelectrophilic substitution, is more effective than the Hammett relationship incorrelating substituent effects on the rate of alkaline hydrolysis of arylacetates.ll0The Ingold-Tuft relationship.The Taftlll separation of polar and stericeffects has been criticised by a number of workers 112 and alternative methodsof estimating Es parameters have been proposed:113 one involves an inter-esting calculation of substituent volumes using the CH, group as a refer-ence.ll3u There is also evidence, from the alkaline hydrolysis of alkylesters, that steric infiuences of substituents in the alkyl component areloa (a) R. I. Walter, J . Amer. Chem. SOC., 1966, 88, 1923; ( b ) ibid., p. 1930.lo4 E. T. Strom, J . Amer. Qhem. SOC., 1966, 88, 2065.lo6 (a) M. M. Bursey and F. W. McLafferty, J . Amer. Chem. SOC., 1966, 88, 629;106 G. B. Barlin and D.D. Perrin, Quart. Rev., 1966,20,74; J. Clark and D. D. Perrin,107 (a) M. Charton, J . Org. Chem., 1966, 31, 3745; ( b ) ibid., p. 2991, 2996; (c) ibid.,108 A. Ceccon, I. Papa, and A. Fava, J . Amer. Chem. SOC., 1966, 88, 4643.log Y. Yukawa and Y. Tsuno, Bull. Chern. SOC. Japan, 1959,32, 971.110 5. J. Ryan y d A. A. Humffray, J . Chem. SOC. ( B ) , 1966, 842.111 R. W. Taft, Steric Effects in Organic Chemistry,” ed. M. S. Newman, ChapmanI l a K. Bowden, Ganad. J . Chem., 1966, 44, 661; P. A. Ten Thije and M. J. Ja;nssen,113 (a) V . I . Kodolov, Zhur.$z. Khim., 1966, 40, 56; (b) M. Friedman and J. S. Wan,( b ) ibid., p. 4484.ibid., 1964, 18, 295.1965, 30, 3341; ( d ) ibid., p. 3346; ( e ) ibid., 1966, 31, 3739.and Hall, London, 1956, p.566.Rec. Trav. chim., 1965, 84, 1169.J . Org. Chem., 1966, 31, 2888CHALLIS : REACTION MECHANISMS 287different from those exerted by the same species in the acyl component ofesters.ll4 In the absence of experimental data, it appears that groupelectronegativities calculated by the method of electronegativity equalisa-tion,ll5 can be used to estimate CT* parameters.ll6 A reassuring note comesfrom a new investigation of C-H stretching vibrations in substituted cyclo-propanes, which shows, contrary to recent conclusions, that their frequenciescorrelate better with o*- than a-parameters.l17Electrophilic Aromatic Substitution.-A recent review summarises thepresent position in regard to various reactivity indices and discusses theirapplication to aromatic substitution ;I18 also free-electron MO calculationshave been carried out for electrophilic and radical substitution and theresults are compared with the Huckel MO method.ll9 The mechanisticutility of kinetic isotope-effects in aromatic substitutions has been discussedfurther by Olah.12*On the experimental side, mercuration of arenes in triffuoroacetic acidseems to be free of the many complications found in acetic acid:121 partialrate factors correlate well with CT+ giving p = -5.6S.l2lC The rates of photo-catalysed protodemercuration of aromatic mercury chlorides also correlatewith cr+ parameters and the initial proton-transfer is slow.However, C1-facilitates ejection of HgCl, in the second fast step, and transition-statesolvation must also be important as the rates are entropy cont,rolled.lZ2The heterogeneous exchange between metallic mercury and mercury diarylsfollows an X E ~ mechanism involving the symmetrical transition-state ( 7).123Aromatic sulphonation has been examined in connection with kineticisotope-effects for substitution in ben~ene,l~4~ orientation in t-butylben-zenes 124b and dealkylation in t-butylbenzenesulphonic acids; the latter is athree-step process involving desulphonation, dealkylation, and resulphona-tion of the benzene residue, in that order.12&There has been considerable interest in various aspects of aromatichydroxylation. Nuclear substitution by arylsulphonyl peroxide appears to114 R.W. A. Jones and J. D. R. Thomas, J . Chem. SOC. ( B ) , 1966, 661.116 J.E. Huheey, J . Phys. Chem., 1966, 70, 2087; ibid., 1965, 69, 3284.11* J. E. Huheey, J . Org. Chem., 1966,31, 2365.11' P. G. Grassman and F. V. Zalar, J. Org. Chern., 1966, 31, 166.11* H. H. Greenwood and R. McWeeny, Adv. Phys. Org. Chem., 1966,4, 73.llB J. I. Fernhdez-Alonso, A. Llinares, and R. Domingo, Anales real SOC. espaii. 3%.18* G. A. Olah, J . Tenn. Acad. Sci., 1965, 40, 77.( a ) H. C. Brown and R. A. Wirkkala, J . Amer. Chem. SOC., 1966,88,1447; ( b ) ibid.,122 R. D. Brown, A. S. Buchanan, and A. A. Humffray, Austral. J . Chem., 1965,laa D. R. Pollard and J. V. Westwood, J . Amer. Chem. SOC., 1966, 88, 1404.( a ) H. Cerfontajn and A. Telder, Rec. Trav. chim., 1965, 84, 1613; ( b ) J. 11.Quim., 1965, 61, 13,1059.p.1453; (c) ibid., p. 1456.18, 1607, 1513.Arends and H. Cerfontain, ibid., 1966, 85, 93; (c) ibid., p. 358288 ORGANIC CHEMISTRYbe a heterolytic process,125 and is therefore similar to the reaction of dialkyl-peroxydicarbonates under Friedel-Crafts conditions : 26 however, in theabsence of Friedel-Crafts catalysts, the latter may react by way of a free-radical process.127 Hydroxylation by hydrogen peroxide occurs readily inthe presence of Fes+ and catechol catalysts, probably via a complex homolyticpath rather than a straightforward attack by the OH radical.12* Unlikeother tetramethylbenzene isomers that form phenols, durene reacts withacidic peroxides to form the dienone (8),129 and therefore resembles hexa-alkylbenzenes .l 30The expected smooth electrophilic substitution of tetracyanopentadienylanions has been examined by several workers.131Alkylation and acylation.The ready reactions of transient carboniumions produced by the deamination of aliphatic amines are well documented.An interesting variation of this process has been discovered by Olah’sgroup, who find that alkylation occurs readily with either N-alkylsul-phinylamines or alkyl isocyanates in the presence of nitrosonium salts.ArH + RNSO + NO+X-+ArR + N, + SO, + HXArH + RNCO + NO+X- + ArR + N, + CO, + HXAcylation occurs similarly when the reaction is carried out with the correscponding acyl compounds. The isomer distributions generally are typical ofan electrophilic reaction ( p > o >> m) and there is evidence for theformation of free carbonium The isopropylation of toluene, how-ever, gives > 90% of 0-cymene,13~ and this unusual result is attributed torearrangement of intermediate dimethylarylcarbonium ions formed fromthe normal products under the experimental conditions. 133Further studies of arene alkylation by amines under diazotisation con-ditions show that substrate reactivities (ktoluenJkbmene = 1.5) are verysimilar to those observed in Friedel-Crafts reactions 134 and there is noArH + RNH, + NO+X-+ArR + N, + H,O + HXevidence for the special solvent cage effects suggested re~ent1y.l~~ Substratereactivities and isomer distributions in these reactions have also been deter-mined by independent kinetic-measurements ;I36 the results stand in good125 R.L. Dannley and G. E. Corbett, J . Org. Chm., 1966,31, 163.146 P. Kovacic and M. E. Kurz, J. Org. Chem., 1966, 81, 2011, 2459.1%’ P. Kovacic and M. E. Kurz, J . Amer. Chem. SOC., 1966, 88,2068; cf. J. c. ~TELI~O,128 G. A. Hamilton, J. P. Friedman, and P. M. Campbell, J. Amer. Chern. ~ o c . ,1 2 9 H. Hart, P. M. Collins, and A. J. Waring, J . Amer. Chem. SOC., 1966, 88, 1005.130 H. Hart and R. M. Lange, J. Org. Chem., 1966, 31, 3776.131 R. C. Cookson and K. R. Friedrich, J . Chem. SOC. ( C ) , 1966,1641 ; K. R. Friedrich,Angew. Chem., Internat. Edn., 1966, 5, 420; cf. 0. W. Webster, J. Amer. Chem. SOC.,1966, 88, 3046.134 G. A. Olah, N. Friedman, J. M. Bollinger, and J. Lukas, J . Amer. Chern. SOC.,J . Org. Chem., 1966, 31, 3615.1966, aa, 6266,6268.1966, 88, 5328.5785; A.T. Jurewicz, J. H. Bayless, and L. Friedman, ibid., p. 5788.lS3 G. A. Olah and N. Friedman, J. Amer. Chm. SOC., 1966, 88, 6330.13* G. A. Olah, N. A. Overchuck, and J. C. Lapiere, J. Arner. Chem. SOC., 1966, 87,136 D. E. Pearson, Ch. V. Breder, and J. C. Craig, J. Amer. Chem. Soc., 1964, 86,5054.136 G. A. Olah and N. A. Overchuck, J. Amer. Chem. SOC., 1966, 88, 6786CHALLIS BEACTION MECHANISMS 289agreement with data obtained from competitive experiments showing thelatter are reliable a t least for alkylation (however, see p. 291). The simi-larities between alkyl chloroformate-&+ catalysed and Friedel-Craftsakylation have also been noted.137Several investigators have inquired into alkylation under Friedel-Crafts conditions.Kinetic studies support last year's spectral evidencefor the formation of oriented n-complexes (9) a t low temperature. Sub-stitution arising from decomposition of this n-complex is quite selective(k,,,,,,/k,,,, = 9.4), thus the reagent must be the weakly electrophilicdonor-acceptor complex rather than any form of carbonium ion. Formationof the a-complex is slow to give 100% p-t-butyltoluene; steric factors pre-vent substitution in the o-position.13* Other studies have been concernedwith substitution by but adiene ,139 isoprene, 140 and gem- dihalo cyclopro-panes;l41 the latter react via an allylic ion, which attacks the aromatic ringand then undergoes cyclisation to form an indene.14l Cycloalkylation withvarious alkyl chlorides has also been examined further.142 Crystallinezeolites catalyse the alkylation of simple aromatic compounds giving pre-dominantly o- and p-orientation and these substitutions have all the characterof Friedel-Crafts reactions.lP3Kinetic studies of the tritylation of phenol and its alkyl ethers againshow that electron release by OH is anomalously high compared tothe invocation of hydrogen-bonding with the solvent, rather than simplehyperconjugation,lg5 to explain this result, receives support from relatedstudies with catechol and its monoethers.In this case substitution isalways para to the OH group, suggesting extensive hydrogen bonding withthe ether oxygenThe solvent appears to be an important factor controlling orientation forFriedel-Crafts acylation in phenant hrene, 146a 1,3,5- triphenylbenzene , 146b 2-methoxy-,l4& and Z-bromonaphthalene.146d Logarithmic rates for the18? P.Beak, R. J. Trancik, J. B. Mooberry, and P. Y. Johnson, J . Amer. Chm. SOC.,Is8 R. Nakane and A. Natsubori, J . Amer. Chem. SOC., 1966, 88, 3011.189 T. Inukai, J . Org. Chem., 1966, 31, 1124.14* E. A. Vdovtsova, Zhur. org. Khim., 1965, 1, 2192.141 L. Skattebd and B. Boulette, J . Org. Chem., 1966, 31, 81.lo= A. A. K,haIuf and R. M. Roberts, J . Org. Chem., 1966, 31, 89; D. L. Ramsey,ibid., p. 3595.la3P. B. Venuto, L. A. Hamilton, P. S. Landis, and J. J. Wise, J . Catalysis, 1966,5, 81.144 (a) G. Chuchani, H. Dlaz, and J. Zabicky, J . Org. Chm., 1966, 31, 1573; ( b ) N.Barroeta, G.Chuchani, and J. Zabicky, ibid., p. 2330.lr6B. C. Challis, Ann. Reports, 1965, 62, 258.(a) N. P. Buu-HOT, P. Mabille, and Do-Cao-Thang, BUZZ. Soc. china. France,1966, 180; ( b ) G. E. Lewis, J . Org. Chem., 1966, 31, 749; (c) R. B. Girder, P. H. Gore,and J. A. Hoskins, J . Chern. SOC. (C), 1966, 181; ( d ) ibid., p. 618.i 9 6 6 , w , 4288290 ORGANIC CHEMISTRYreaction of toluene with substituted benzoyl chlorides correlate better with0 +- than a-parameters, suggesting that the reagent under Friedel-Craftsconditions may be the benzoyl cation.147Hydrogen isotope exchunge. An interesting feature of A-&2 hydrogenexchange in substituted NN'-dimethylanilines is that AS# varies from +27e.u. for o-C1 to -17.5 e.u. for p-Br substituents.These large differences em-phasise the improbability of correlating AS# with changes in the integralnumber of solvating water molecules,148 although they roughly correspondwith the acidity of the methylene hydrogens in the transition state.149An important comparative kinetic study of hydrogen exchange in[4- 3H]-m-xylene and desilation in p-chlorophenyltrimethylsilane by Eaborn andco-workers I5O shows the response of both reactions to medium changes inCI?,CO,H is remarkably similar, suggesting a common A-SB2 mechanism.This conclusion finally eliminates 4-centre transition states as a possibility indesilation rea~ti0ns.l~~ However, substituent effects in the two reactions arequite different (Pdetritistion/PdesII&ion = 1*7), probably because of the in-cidence of pn-dn bonding stabilising the initial state of the silane (11).Acid-catalysed hydrogen exchange in azulenes has been studied further 163and the reactivity of various nuclear po~itionsl5~a is compared with otherrelated non-benzenoid compounds ;152b exchange rates for 3-substituted[ l-2H]azulenes correlate with benzene a,-parameters giving p = -4.35.lS2cAnother example of acid-catalysed exchange in cationic species has beenreported, this time for the conjugate acid (12) of diarylethylene~.~~~The investigations of Streitwieser and his co-workers 154 into themechanism of base-catalysed aromatic-hydrogen exchange in solvent cyclo-hexylamine are of related interest.Fairly large differences in the primaryisotope-effects for lithium cyclohexylamide ( 7cD/kT = 1.5) 154a and cesiumcyclohexylamide ( kD/kT = 2.5) 154c catalysts are not completely understood,but it is suggested that, whereas a direct proton-abstraction is rate-determining for cesium cyclohexylamide, a two step process (Scheme 1)in which internal return is important (k-l > k,) operates for the lithiumbase.Rates of exchange for both bases, however, appear to reflect therelative acidities of the C-H bonds.154b.d147P. J. Slootmakeers, A. Rasschaert, and W. Janssens, BulZ. SOC. chim. beZges,1966, 75, 199.148 L. L. Schaleger and F. A. Long, Adv. Phgs. Org. Chem., 1963, 1, 1.149 I. Lee and F. R. Kendall, J . Arner. Chem. Soc., 1966, 88, 3813.160 C. Eaborn, P. M. Jackson, and R. Taylor, J . Chem. SOC.( B ) , 1966, 613.151 See ref. 145, p. 256.162 (a) C. Weiss, Tetrahedron, 1966, 22, 145; (b) C. W e k and D. Schonfeld, ibid.,153 C. A. Kingsbury, Tetrahedron Letters, 1966, 2539.1 5 4 (a) A. Streitwieser, R. G. Lawler, and C. Perrin, J. Amer. Ch.em. SOC., 1965, 87,p. 2611; (c) C. Weiss, W. Engewald, and H. MiiUer, ibid., p. 825CEIALLIS : REACTION MECHANISMS 291SCHEME 1Attention recently has also focused on metal-catalysed aromatic-hydro-gen exchange, and a review covers progress up until 1964.lS5 These reactionshave been discussed by Garnett and his co-workers in terms of two alterna-tive n-complex mechanisms for platinum catalysts 156 and other Group VIIImetals ;I5‘ platinum appears to be themost efficient catalyst,157 althoughnickelis more selective.15s Recent work has included catalysed exchange in anilineY159anisole,16* and t-butylbenzenes,161 as well as interchange of hydrogenbetween deuteriated and normal arenes.162 The partial rate factors forplatinum-catalysed exchange in mono-substituted benzenes show largesteric but negligible electronic effects,l63 supporting the ‘dissociative’ ex-change mechanism (Scheme 2) of Garnett.156 The overall reactivity,however, lies in the order usually observed in electrophilic substitution (k,NH,> F > C1 > CN etc.and this is taken to indicate that step (b) is ratecontrolling.163P tYPt P t P t P t P t Pt PtSCHEME 2Nitration. A review on the mechanism of nitration in organic solvents isone of many interesting articles in a recent tribute to Sir Christopher Ingold.This review cites further convincing evidence, from studies with dibenzyl,that partial diffusion control of the reaction rates is responsible for the lowsubstrate selectivities obtained for nitronium salt nitration in competitiveexperiments.16*Details of kinetic studies on the nitration of aniline and some N-methy-5383; (b) A.Streitwieser and R. G. Lawler, ibid., p. 5388; (c) A. Streitwieser and R. A.Caldwell, ibid., p. 5394; ( d ) A. Streitwieser, R. A. Caldwell, R. G. Lawler, and G. R.Ziegler, ibid., p. 5399.166 J. L. Garnett and W. A. Sollich-Baumgartner, Adv. Catalysis, 1966, 16, 95.166 J. L. Garnett and W. A. Sollich-Baumgartner, J . Phys. Chem., 1965, 69, 1860;cf., Austral. J . Chem., 1961, 14, 441.lS7 J.L. Garnett and W. A. Sollich-Baumgartner, Austral. J. Clwn., 1965, 18, 1003.ls* P. J. Collin and C. G. MacDonald, Austral. J . Chem., 1966, 19, 513.159 H. Hagiwara and E. Echigoya, Bull. Chem. SOC. Japan, 1966, 39, 1683.180 R. B. Anderson and C. Kernball, J . Catalysis, 1966, 6, 82.161 R. J. Harper, S. Siegel, and C. Kemball, J. Catalysis, 1966, 6, 72.163 J. L. Garnett and W. A. Sollich-Baumgartner, J. Catalysis, 1966, 5, 244.16* R. F. Fraser and R. G. Renaud, J . Amer. Chem. Soc., 1966,88,4365.164 J. H. Ridd, “ Studies on Chemical Structure and Reactivity,” ed. J. H. Ridd,Methuen, London, 1966, p. 133292 OBQANIC CHEMISTRYlated derivatives in 90-100% sulphuric acid clearly show that the mainreaction is between the nitronium and anilinium i 0 n ~ .l 6 5 An estimation ofthe partial rate factors [fm/fp = 0-83 for hNH,+] demonstrates thatinductive electron-withdrawal by the positive poles deactives themeta- and para-positions almost equally,lesb in contrast to the nitro-group um/f.. = 22 for ArN02]le6 in which resonance interaction is alsoimportant. However, overall deactivation decreases along the seriesme,+> NMe,H+> NMeH,+> N€€,+, and this is attributed to differencesin solvation.l65* A similar conclusion has been reached from independentn.m.r. studies (see p. 277).8 Recognition of electrophilic substitution incationic species becomes increasingly common, and another example has beencited to account for the unusual orientation in the nitration of 3-toluene-p-~ulphonamidoveratrole.~~7 Also substituent effects in the N-nitrosation ofprimary and secondary aromatic amines in concentrated acids stronglysuggest that these reactions involve the conjugate acid of the amines, inaccord with earlier conclusions.le8Rearrangement of the t-butyl side-chain accompanies the nitration of2,4,6-tri-t-butylnitrobenzene and leads to several unexpected products[(14) to (17)].lSg The formation of the toluene derivatives (16) and (17) sug-gests that the intermediate alkylcyclohexadienyl cation has sufficientFrom (13) 58.9% 4.6% 34.3% 2-2y0From (13)-[3,5-aHa] 32.2% 6.4% 58.3% 3.1%stability for rearrangement [ (18) +( 19 J and elimination of the isopropyliumion to O C C W .~ ~ ~ = The higher percentage of rearranged products with ring-deuteriated reactant is consistent with this interpretation and a primarykinetic isotope-effect (kE/kD = 1.8) indicates that proton loss from (19) isslow.169bNO2(13) f NO,++ B u ' ~ NO2 7 . B u t ~ ~ ~ z + (16)But M e(a) M. Brickrnann and J. H. Ridd, J . Chem. SOC., 1965, 6845; ( b ) M. Brickmann,J. H. P. Utley, and J. H. Ridd, a i d . , p. 6851.166 A. D. M6sure and J. G. Tillett, J. C h m . SOC. ( B ) , 1966, 669.16' F. Bell and A. S. Millar, J. Chm. SOC. (C), 1966, 375.168 E. Kalatzis and J. H. Ridd, J. Chem. SOC. ( B ) , 1966, 529; E. C. R. de Fabrizio,E. Kalatzis, and J. H. Ridd, ibid., p. 533; cf. M. N. Hughes, T. D. B. Morgan, andG. Stedman, Chem. Comm., 1966,241.169 (a) P. C. Myhre and R. A. Beug, J . Amer.Chem. SOC., 1966, 88, 1568; (b) ibid.,p. 1569CHALLIS : REACTION MECHANISMS 293Anomalously high and solvent dependent o : p ratios for the nitration ofbiphenyl have always been difficult to understand and it is now suggestedthat a n-complex between NO2+ and biphenyl forms initially, which thenrearranges to the most accessible a-complex at the ortho-position of the secondaromatic nucleus.l70 This mechanism resembles the recent propositions toaccount for high o : p ratios in aromatic ethers and anilides.171 However,the solvent dielectric may also be important in determining o : p ratios.172The reactions between nitric acid and alkylbenzenes in CF,CO,€€ do notfollow complex kinetics, as observed in solvent CH3C02H, and substratereactivity is normal ( ktoluene/kbenzene = 28) .121a Other recent investigationshave been concerned with orientation in 1,2,di-t-butylbenzene 173 and dial-kylphenoIs,l7* and the effect of added salts on nitration rates in anhydroussulphuric acid ; added salts cause the rate to pass through a maximum and thisis not due to changes in the activity coefficient of the neutral sub~trate.l7~The third-order dependence on nitric acid concentration for the nitration ofN-methyl-N-nitrosoaniline in carbon tetrachloride has been tentativelyrationalised by a complex mechanism involving intermolecular nitrosation.17*Hubgemtion.Aromatic bromination with bromine is an uncomplicatedaecond-order process in CF,C02H (unlike the reaction in CH,CO,H) and thissolvent will be ideal for detailed mechanistic studies.121as Substituenteffects appear to be accentuated in CF3C02H and the reactivity ratioktoluene/kbenzene = 2580 is the highest recorded for electrophilic substitutionin these substrates.However, the relative rates for monoalkylbenzenes donot steadily decrease with increased branching in the alkyl substituent, as isusual, but lie in the order CH, < C2H,< CH(CH,),> C(CH,),. This sug-gests that a fine balance exists between inductive and hyperconjugativeinteractions, facilitating n- and a-complex formation, respectively. Thepartial rate factors for toluene (below) show that reaction rates are fasterCF,CO,H 136 : 1 : 1270CH,CO,H 109 : 1 : 440fo : fm : f*with less o-substitution in CF,C02H compared to CH,CO,H.The diminishedo-substitution would be consistent with some form of solvated molecularhalogen being the reagent. Further results are awaited with interest.121bAn elegant kinetic study by Baliga and Bourns 177 of the effect of addedbromide ion on the molecular bromination of sodium-p-methoxybenzene170 R. Taylor, J . Chem. SOC. ( B ) , 1966, 727; Tetrahedron Letters, 1966, 6093.171P. Kovacic and J. Hiller, J . Org. Chem., 1965, 30, 2871; cf., R. 0. C. Normanand G. K. Radda, J. Chem. SOC., 1961, 3030; J. R. Knowles and R. 0. C. Norman,ibid., p. 3888.17* A. K. Sparks, J . Org. Chem., 1966, 31, 2299.178 B. Van de Grad and B. M. Wepster, Rec. Trav. chim., 1966, 85, 619.17' G. A. Zlobina and V. V. Ershov, Izvest. Akad. Nauk S.S.S.R., Ser.Kh;m., 1966,176 T. G. Bonner and F. Brown, J . Chem. SOC. ( B ) , 1966, 658; cf. B. Surfleet and176 T. G. Bonner and R. A. Hancock, J . Chem. SOC. ( B ) , 1966, 972; T. G. Bonner,177 B. T. Baliga and A. N. Bourns, Canad. J . Chem., 1966, 44, 379.189.P. A. H. Wyatt, J . Chem. SOC., 1965, 6524.R. A. Hancock, R. L. Williams, and J. C. Wright, Chem. Comm., 1966, 109294 ORGIANIC CHEMISTRYsulphonate and its o-deuteriated analogue provides firm evidence for a twostep process (Scheme 3). The ratio kH3/kD, = 7.0 indicates that breakdownof the intermediate is slow; surprisingly, there is a negligible secondaryisotope-effect on formation of the intermediate (kHl/kD1 = 1.00 & 042).L, ArH + Br, &<:r + Br- + ArBr + H+k,SCHEME 3Related studies with 34S-1abelled substrates show that elimination ofsulphonic acid is also rate-determining in the accompanying bromodesul-phonation reaction.178 Substantial primary deuterium isotope-effects havealso been noted for the reaction of bromine with 2,4-dibromo- ( kH/kD = 4-76)and 2-bromo-1,3,5-trimethoxybenzene (kH/kD = 3-57), but not for tri-methoxybenzene, itself.79 These results again indicate that steric conges-tion in the transition state causes a shift in the rate-determining step.ls0Considerable dealkylation (up to 50%) occurs in the substitution of1,4-di-t-butylbenzene with bromine in carbon tetrachloride ;181 bromination of4-acetamido-3-nitroanisole produces 2,3,4,5-tetrabromoanisole and elimina-tion of the acetamido- and nitro- groups may be concerted.lS2The partial rate factors for the chlorination of several diphenylalkanesand 4,5,9,10-tetrahydropyrene have been related to the way in which theinductive effect of phenyl is transmitted through the saturated side-chain inbridged biphenyls.The results are consistent with considerable electronwithdrawal from the neighbouring aromatic nucleus l S s and this bears onrecent discussions on the nature of inductive interactions. (see p. 283).Other recent investigations demonstrate that partial rate factors for chlorina-tion in m- and p-chloroacetanilides conform with the additivity principle,ls4whereas those for polyalkylbenzenes and biphenyls do not, presumablybecause of steric interactions.183 Orientation in several naphthalene deri-vatives has been examined,l85 and in one instance leads to unexpectedre~ults.18~CRecent work has also provided definitive evidence €or the long-suspectedN-chloramine intermediary in nuclear chlorination of aromatic amines bycalcium hypochlorite, and it is evident that N-chloro-N-methylamine issurprisingly stable in carbon tetrachloride.186Direct molecular iodination of substituted benzenes has also been178 B.T. Baliga and A. N. Bourns, Canud. J . Chem., 1966, 44, 363.lT9 E. Helgstrand, Acta Chm. Scand., 1965, 19, 1683.lB0 See ref. 145, p. 259.181 J. M. A. Baas and B. M. Wepster, Rec. Truv. chim., 1966, 85, 457.18s C. R. Harrison and J. F. W. McOmie, J . Chem. SOC. (C), 1966, 997.188 P. B. D. de la Mare, E. A. Johnson, and J.S. Lomas, J . Chem. Soc., 1965, 6893.164 0. M. H. el Dusouqui and M. Hasaan, J. Chem. SOC. ( B ) , 1966, 374.18s (a) E. R. Ward and A. Hardy, J . Chem. SOC. ( C ) , 1966, 1038; ( b ) J.-C. Richer andY. P6pin, Canad. J . Chem., 1965, 45, 3443; (c) W. Adcock, M. J. S. Dewar, and G. R.Johnson, Tetrahedron Letters, 1966, 5307; (d) L. I. Denisove, N. A. Morozova, V. A.Plakhov, and A. I. Tochilkin, Zhw. org. Khim., 1966,2,30; ( e ) G. P. Petrenko and A. N.Tel’nyuk, ibid., p. 722.186 P. Haberfield and D. Paul, J . Amer. Chem. SOC., 1965, 87, 5502CHALLIS : REACTION MECHANISMS 295studied,187 and in 20% oleum the product orientation is consistent witha reaction of the I,+ reagent.187~ The iodination of aniline by iodine mono-chloride in aqueous HC1 leads to complex kinetics, but these rationalise witha slow proton loss from the a-bonded intermediate,lg8 consistent withdeductions recently made in connection with protodeiodination.Furtherinformation has been presented on the reaction of iodine monochloride withpolyinethylbenzenes and the most important reactions are nuclear iodinationand side-chain chlorination. Both are believed to be polar in nature andprobably proceed via a common intermediate.lgOThe mechanisms of addition reactions that often accompany halogenationin condensed aromatics have been thoroughly discussed in a recent review lQ1a8nd the stereochemistry of these additions to naphthalene lg20 and cyclo-octatetraene 192b under various conditions has now been reported.Nucleophilic Aromatic Substitution.-Two of the most rapidly develop-ing areas of aromatic substitution concern bimolecular and aryne nucleophilicdisplacements, and these, together with the formation of Meisenheimercomplexes and substitution in polyfhoro-aromatics, are discussed separatelybelow.The number of nucleophilic displacements either catalysed or induced bylight grows rapidly and substitutions by CN- (ref.193), OH- (ref. 194) andprimary and secondary amines 195 have been reported for nitroanisoles. Themechanism(s) of these reactions is not understood, but generally it is believedthat the nueleophile interacts directly with the photo-excited aromatic~pecies.~g~~ It is of interest to note, however, that in the flash-photolysis ofanisoles in aqueous solution photoionisation with the formation of eaq- andphenoxymethyl radicals (PhOCH,.) appears to be the primary photo-chemical process.lg6 The structure of the nucleophile must be important, too,8s methoxide is displaced more readily from para- than meta-nitroanisole byamines, but the reactivity is reversed with OH-.lQ5 For the displacement ofmethoxide from m-nitroanisole, 1 8 0 experiments establish that cleavage ofthe aryl-oxygen bond occurs,194b unlike the thermal reaction in alkalinemedia,lg7 and there is evidence for the formation of several intermediatesin the related hydrolysis of 3,5-dinitroanisole.lg8 A somewhat different18' (a) J.Arotsky, R. Butler, and A. C. Darby, Chem. Comm., 1966, 650; ( b ) H.lE8 F. M. Vainstein, E. I. Tomilenko, and E. A.Shilov, Kinetiku i Kataliz, 1966,lSg See ref. 145, p. 256.lgo R. M. ICeefer and L. S. Andrews, J. Org. Chem., 1966, 31, 541.lgl P. B. D. de la Mare, J. S. Lomas, and V. del Olmo, Bull. SOC. chim. France, 1966,1157.lea (a) P. B. D. de la Mare, M. D. Johnson, J. S. Lomas, and V. S. del Olmo, J . Chern.SOC. ( B ) , 1966, 837; (b) R. Huisgen, G. Boche, W. Hechtl, and H. Huber, Angew. Chem.,Internat. Edn., 1966, 5, 585.lg3 R. L. Letsinger and J. H. McCain, J. Amer. Chem. SOC., 1966, 88, 2884.lQ4 (a) D. F. Nijnoff and E. Havinga, Tetrahedron Letfers, 1965, 4199; (a) R. 0. deJongh and E. Havinga, Rec. Traw. chim., 1966, 85, 275.lg6 M. E. Kronenberg and A. Van der Heyden, Bec. Trav. china., 1966, 85, 56.lg6 H. I. Joschek and L.I. Grossweiner, J . Amer. Chem. SOC., 1966, 88, 3261; H. I.Joschek and S. I. Miller, ibid., p. 3273.lg7 V. A. Ignatov and S. M. Shein, Zhw. orq. Khim., 1965, 1, 1951.lQ8 J. Cornelisse and E. Havinga, Tetrahedron Letters, 1966, 1609.Suzuki, K. Nakamura, and R. Goto, Bull. Chm. SOC. Japan, 1966, 39, 128.7, 33296 ORGANIC CHEMISTRYreaction has been reported by Letsinger and Wubbels lg9 for several nitroarenesin concentrated HC1, where reduction of the nitrogroup (to NH,) and dis-plaoement of three aromatic hydrogens by chlorine (Scheme 4) is the mainNO2 0 __f $jc, + CI c16.' \ ciOH OH OHSCHEME 4(7 1 Yo) (16%)reaction on irradiation with U.V. light of greater than 290 mp. The rate ofsubstitution depends on both H+ and C1- concentrations, and nucleophilicattack by C1- on the photoexcited protonated nitrobenzene is suggested lQ9by analogy to the photoinduced conversion of azobenzene in acetyl chlorideto NN'-diacetyl-4-chlorohydrazobenzene.200 However, another clue to themechanism may lie in the photochemical reduction of nitrobenzene itself.20'Full details have now been published of the photoinduced substitution byCN-, N3-, and OCN- in polyhalogenated clovoboranes ; photoinducedheterolysis of the boron-halogen bond occurs, followed by addition of theanion.202 The early work on nucleophilic photo-substitutions has beenreviewed by Havinga .SO3Further details have also been given of the novel amination with trichlor-arnines under Friedel-Crafts conditions.,04 The mechanism is still tentative(Scheme 5 ) , but the relative reactivities of alkylbenzenes 20** are consistentwith a rate-determining initial electrophilic attack by Clf [step (a)], and thepredominant formation of m-alkylanhes suggests the second step involvesan unidentified arnino-species (written as NH,-) in a nucleophilic addition-elimination sequence [step (b)].With halogenobenzsnes, considerable dis-placement of the residual halogen also occurs, presumably via a similarnucleophilic displacement [step (c)] .204c These studies have been extended toX+ CI+ % slowCISCHEME 5lg9 R. L. Letsinger and G. G. Wubbels, J . Amer. Chem. SOC., 1966, 88, 5041.201 R. Hurley and A. C. Testa, J . Amer. Chem. SOC., 1966, 88, 4330.202 S. Trohenko, J . Amer. Chem. Soc.,,1966, 88, 1899.203 E.Havinga, 13th Solvay Congress of Chemistry, Brussels, 1965.204 (a) P. Kovacic, J. A. Levisky, and C. T. Goralski, J . Amer. Chem. SOC., 1966, 88,100; ( b ) P. Kovacic and J. A. Levisky, ibid., p. 1000; (c) P. Kovacic and J. F. Gormish,ibid., p. 3819.G. E. Lewis and R. J. Mayfleld, Tetrahedron Letters, 1966, 269CHALLIS : REACTION MECHANISMS 297consider substitution by dialkylhaloamines 205 and the formation of t-alkyl-amines by the reaction of trichloroamine with either methylcyclohexane orp-cymene.206 In the absence of Friedel-Crafts catalysts, nuclear aminationby N-haloamines appears to be a homolytic process, and these reactions arediscussed on page 304.As a result of n.m.r. studies,207 doubt has been cast on Insole and Lewis’claim 208 that scrambling of the nitrogen atoms [Ar15NiN+] -+ [Ar Ni15N+]accompanies decomposition of arenediazonium ions.However, the isotopeexchange experiments have been repeated and these new results support theoriginal claim.209 The decomposition of o-halogenobenzenediazonium ionsin %-sodium methoxide proceeds vk anion intermediates, although a freeradical process operates in mildly alkaline methanol,21*a and the formation ofbiphenyls as a minor product from the decomposition of benzenediazoniumborofluoride in aromatic solvents may involve phenyl diradical cation inter-mediates.210b An interesting reaction results in the displacement of thenitro-group by chloride when p-substituted o-nitrobenzenediazonium ionsare heated in concentrated hydrochloric acid ; the substituent effects areconsistent with nucleophilic attack by Cl-.211Other recent work includes further studies of the Ullmann reaction,212 inwhich a similarity to copper-catalysed decarboxylation has been noted.a12cSeveral workers have reported on smooth nucleophilic alkylation of aromaticcompounds with dimethyloxosulphonium methylide [( CH,),SO CH,-] 21and with methylsulphinyl carbanions [CH,SO CH2-1, generated fromdimethyl sulphoxide by the addition of several bases.214Last year’s Report referred to convincingevidence for the formation of tetrahedral intermediates in these reactions.Confirmation of their formation now comes from the decrease in the leavinggroup oxygen isotope effect for the reaction of 2,4-dinitrophenyl phenyl etherwith pyridine in aqueous dioxan (Scheme 6), as the rate-determining stepBimolecuhr displacements.[NaOH] M. k16/k1*0.005 1.01090.033 1.00700.149 14024changes from k, to kl with increasing concentration of the hydroxide ioncatalyst.215 There is also further evidence that the experimental hydrogen205 V.L. Heasley, P. Kovacic, and R. M. Lange, J. Org. Chem., 1966, 31, 3050.206 P. Kovacic, R. J. Hopper, S. S. Chaudhary, J. A. Levisky, and V. A. Liepkalns,207 A. K. Bose and I. Kugajevsky, J . Amer. Chem. Soc., 1966, $8, 2325.208 J. M. Insole and E. S. Lewis, J. Amer. Chem. SOC., 1964, $6, 32.209 E. S. Lewis and R. E. Holliday, J. Amer. Chem. SOC., 1966, $8, 6043.210 ( a ) J. F. Bunnett, D. A. R. Happer, and H.Takayama, Chem. Comm., 1966, 367;(b) R. A. Abramovitch and J. G. Saha, Canad. J . Chem., 1965, 43, 3269.211 Z. J. Allen and J. Podstata, Coll. Czech. Chem. Comm., 1966, 31, 3418.21* ( a ) C. Bjorklund and M. Nilsson, Tetrahedron Letters, 1966, 675; ( b ) A. H. Lewkand T. Cohon, ibid., 1965, 4531; (c) M. Nilsson, Acta Chem. Scud., 1966, 20, 423.218 V. J. Traynelis and J. V. McSweeney, J . Org. Chem., 1966, 31, 243.21c (a) G. A. Russell and S. A. Wiener, J. Org. Chem., 1966, 81, 248; (b) H. Nozaki,Y. Tammoto, and R. Noyori, Tetrahedron Letters, 1966, 1123.215 C. R. Hart and A. N. Bourns, Tetrahedron Letters, 1966, 2995.Chem. Comm., 1966, 232298 ORGANIU CHEMISTRYisotope effects associated with the catalysing base in both solvent benzene 216and water 215 are a function of the catalyst concentration, as required by thetwo-step mechanism.Although these isotope effects are best regarded asprimary (kR3/ED, N 2), their precise origin, and therefore the mechanism ofthe base catalysis also, is still open to question. Three possibilities have beensuggested.215 This uncertainty has long been apparent for base catalysis insolvent benzene, and Bernasconi and Zollinger 2 l 7 now regard the abstruseeffects of various catalysts on the reaction of piperidine with 2,4-dinitro-fluorobenzene to arise from a combination of medium effects and general base-catalysis, along the lines suggested by Bunnett and his co-workers: 218tertiary amines, such as triethylamine, are ineffective for steric reasons andelectrophilic catalysis is only important for methanol.This interpretationis not inconsistent with the primary hydrogen-isotope effect for the analogousreaction of 4-chlor0-3-nitrobenzenetrifluoride.~~~Further support for the two-sta,ge mechanism in bimolecular displace-ments has come from kinetic studies of halogen exchange in 2,4,6-trihalo-genobenzenediazonium ions,219 analyses of solvent effects,220 the incidence ofacid and metal-ion electrophilic catalysis in the reaction of various nucleo-philes with 2,4-dinitrofluorobenzene,221 and the reactivity of amines in halidedisplacement reactions.222 It is also claimed that the tetrahedral inter-mediate formed in the reaction of ethyl malonate with 2,4-dinitrofluoro-benzene is stable in aprotic s0lvents.22~ Miller and his co-workers 224 haveshown that both nucleophilic reactivity and halogen mobility for anion sub-stitution in halogenobenzenes can be predicted quantitatively from thermo-chemical data on the basis of a two-stage reaction.2240 These arguments havebeen extended to a general treatment of nucleophilicity and basicity forseveral reagents 224b and they demonstrate that an extremely fine balanceexists between rate-determining formation and decomposition of the tetra-216 R.L. Toranzo, R. V. Caneda, and J. A. Brieux, J. Amer. Chem. SOC., 1966, 88,3651.21' C. Bernasconi and H. Zollinger, Helv. Chim. Acta, 1966, 49, 103.218 J. F. Bunnett and R. H. Garst, J . Amer. Chem. Soc., 1965,87,3875; J . F. Bunnett219 B. L a m and B.Andersson, Arkiv Kemi., 1966, 25, 367.220 B. 0. Coniglio, D. E. Giles, W. R. McDonald, and A. J. Parker, J . Chem. SOC. (B),221 K. B. L a m and J. Miller, Chem. Comm., 1966, 642.233 H. Suhr, Annalem, 1965, 689, 109; H. Suhr and H. Grub, Ber. Bunsen Gessell-i23P. Baudet, Helv. Chim. Actcc, 1966, 49, 645; cf. J. Bourdais and C. Mahieu,224 (a) K. C. KO, J. Miller, and I<. W. Wang, J. Chem. SOC. ( B ) , 1966, 310; ( b ) D. L.and C. Bernasconi, ibid., p. 5209.1966, 152; R. G. Burns and B. D. England, ibid., p. 864.echnft Phys. Chem., 1966, 70, 544.C m p t . Rend., 1966, 263, C, 84.Hill, K. C. Ho, and J. Miller, ibid., p. 299CHALLIS : REACTION MECHANISMS 290hedral intermediate, which depends on the leaving group, the nucleophile,the ring substituents, and the solvent in accord with experimental hdings.Other theoretical approaches, also based on the two-stage mechanism, havecorrelated activation energies with n-delocalisation energies, 225 and Patai andGotshal,226 also, have discussed the relative strengths of various nucleo-philes in aromatic substitution.Several investigations clearly indicate that the steric effects of o-substi-tuents are not appreciable in bimolecular displacements,227 and in oneinstance this is regarded as evidence for the tetrahedral nature of the tran-sition ~tate.~~'U The studies of Crampton and Gold 228 on the formation ofMeisenheimer complexes (see below) also bear on this issue.Other recentpapers have reported extensive kinetic studies of the hydrolysis and methano-lysis of picryl ethers and halides,229 including the effect of pressure on thesereactions.229uMeisenheimer and related complexes.This topic has been reviewed withspecial emphasis on recent structural assignments from n.m.r. and otherspectral data.230 Crampton and Gold's preliminary account clearlyshows that primary and secondary aliphatic amines form 1 : 2 complexes (20)rather than 1 : 1 zwitterions with 1,3,5-trinitrobenzene in anyhdrous di-methyl sulphoxide. With secondary amines in solvent acetone, however,further slow reactions involving o-bonded intermediates occur and even-tually lead to the formation of NN'-dialky1-4-nitr0aniline.2~~ Tertiaryamines cannot form equivalent 1 : 2 complexes and therefore do not reactin anhydrous dimethyl ~ulphoxide,23~ but in ketonic solvents they catalysethe formation of o-complexes (21) arising from nucleophilic attack of theketo-anion on 1,3,5-trinitroben~ene.23~N.m.r.studies of the interactiom between nitroarylamines and variousbases have confirmed many previous deductions from U.V. spectral data andthe results have an important bearing on the interpretation of acidity-function measurements in basic media (see ref. 17). Dinitroanilines ionise225 S . CarrB, M. Raimondi, and M. Simonetta, Tetrahedron, 1966, 22, 2673; cf. J.Murto, Suomen Kem., 1965, 38, B, 246.226 S. Patai and Y . Gotshal, Israel J . Chem., 1966, 3, 223.2p7 (a) F. Pietra and F. Del Cima, Tetrahedron Letters, 1966, 4453; (b) A. M. Porto,L. Altieri, A. J. Castro, and J.A. Brieux, J . Chem. SOC. (B), 1966, 963; (c) N. E. Sbarbati,J . Org. Chem., 1965, 30, 3365.229 (a) J. Murto and Bf. Kiuttu, Suomen Kern., 1966, 39, B, 14; (b) J. Murto andM.-L. Murto, Acta Chem. Scan&., 1966, 20, 297; ( c ) J. Murto, ibid., p. 303; ( d ) h i d . ,p. 310.230 R. Foster and C. A. Fyfe, Rev. Pure Appl. Chem. (Australia), 1966, 16, 61.Z 3 l M. R. Crampton and V. Gold, Chem. Comm., 1965, 549.232 R. Foster and C . A. Fyfe, Tetrahedron, 1966, 22, 1831.233 R. Foster and C. A. Fyfe, J . Chem. Soc. ( B ) , 1966, 53.M. P,. Crampton and V. Gold, J . Chern. SOC. ( B ) , 1966, 893300 ORGANIC CHEMISTRYonly by proton loss from nitrogen; however, with trinitroanilines bothproton loss and base addition occurs (Scheme 7). The two ions (22) and (23)are in equilibrium and their relative concentrations depend on the solvent,on the basic species and, to some extent, on the character of the N-substi-tuents.228, 234 The addition of alkoxide ions is always at an unsubstitutednuclear position for both trinitroarylamines and polynitroanisoles, but , forthe latter, rearrangement to stable Meisenheimer complexes quicklyo c ~ u r s ; ~ ~ ~ ~ 234 with an excess of methoxide ion, further addition takes place a tunsubstituted nuclear sites in the Meisenheimer complex.235 The relativeease of formation and stabilities of the various complexes has been dis-cussed, and it is concluded that Meisenheimer complexes are poor models forthe transition states of nucleophilic substitutions in substrates containingo-substituents.228The kinetics of Meisenheimer complex formation and decomposition havebeen examined further 236 and full details have been given for the sym-metrical exchange of methoxide ion with nitroaromatic ethers 237. Theresults are interpreted in terms of a two-stage reaction in which tetrahedralcomplex formation is fast for 2,4,&trinitroanisole, but slow for 2,4-dini-troanisole and 4-methoxypyridine- l-oxide. 237 This interpretation needsslight modification in view of Crampton and Gold's 228 results.0 t her related investigations have concerned base - ca t a1 y sed isotopic -hydrogen exchange in polynitrobenzenes. The coloured species formed inthese solutions is identified as the addition complex (24), which exists insolution with small amounts of other ions: of these, (25) is the reactiveintermediate for nucleophilic displacement of NO,, and only the anion (26)leads to hydrogen exchange.238234 K.L. Semis, J . Amer. Chem. SOC., 1965, 87, 5495.2a6 T. Abe, Bull. Chem. SOC. Japan, 1966, 39, 627.T. Abe, T. Kumai, and H. Arai, Bull. Chem. SOC. Japan, 1965,38,1626; J. Murtoand E. Kohvekka, Sumen Kern., 1966, 39, B, 128; J. Murto and J. Vainionpaa, ibid.,p. 133; J. Murto and A. Vitala, ibid., p. 138.237 J. H. Fendler, J . Amer. Chem. Soc., 1966, 88, 1237.288 (a) M. R. Crampton and V. Gold, J . Chem. SOC. (B), 1966, 498; (6) E. Bunceland E. A. Symons, Canad. J . Chem., 1966, 44, 771CHALLIS : REACTION MECHANISMS 301PerJluoroarornutic comlpounds. Isomer distributions for substitution byvarious nucleophilic reagents in pentafluoro- 239a and tetrafluoro-halogeno-benzenes 239b are consistent with Burdon's 240 explanation (reported lastyear) in terms of n-inductive electron repulsion by the halogens destabilisingWheland-type intermediates in the transition state, although steric factorscan also be important.It is dScult, however, to rationalise in this way thepreferential displacement of fluorine (as opposed to chlorine para to hydrogen)in 2,3,4,6- tetrachlorofluoro benzene. 41 Pol yfluoro benzenes yield severalproducts with metal cyanides in methanol and $he orientation is consistentwith substitution fist by CN- and then by methoxide i0n.242An unusual reaction in sulpholane between perfluoro-compounds andhexafluoropropene in the presence of added potassium fluoride results in theSCHEME 8displacement of fluorine by -CF(CF,), (Scheme 8). The reagent is hexa-fluoroisopropyl carbanion formed by the addition of F- to the olefin, and thedisplacement can be regarded as the nucleophilic equivalent of a Friedel-Crafts reaction.243 Other recent studies have examined the fluorination ofpolychlorobenzenes with potassium fluoride 244 and the decomposition offluoroformates.245 Both orientation and reactivity in polyhalogen com-pounds has been discussed, in a somewhat different way from Burrdon's 240approach, on the basis of extensive kinetic data.246Benzyne and related intermediates.A substantial decrease in the p : rnratio with increasing methoxide ion concentration for the formation ofchloroanisole from methanol and 4-chlorobenzyne shows that methoxide ion ismore reactive than methanol towards the aryne.The orientational controlby chlorine arises from a greater stabilisation of negative charge in thetransition state a t the meta (27) than the para (28) position, and this stabilisa-tion should be more important for the weaker, and therefore more selective,H1Me-Y'S-(J- (27)Cl239 (a) J. Burdon, P. L. Coe, C. R. Marsh, and J. C. Tatlow, Tetrahedron, 1966, 22,240 J. Burdon, Tetrahedron, 1965, 21, 3373.241 L. S. Kobrina and G. G. Yakobson, Zhur. obshchei. K h h , 1965, 35, 2055.242 E. Fehlstead, H. C. Fielding, and B. J. Wakefield, J . Chem. SOC. (C), 1966, 708.243 R.D. Chambers, R. A. Storey, and W. R. K. Musgrave, Chem. Comm., 1966,384.244 G. W. Holbrook, L. A. Loree, and 0. R. Pierce, J . Org. Chem., 1966, 31, 1259.245 K. 0. Christie and A. E. Pavlath, J . Org. Chem., 1966, 31, 559; ibid., 1965, 80,&46 K. C. Ho and J. Miuer, Austral. J . Chrn., 1966, 19, 423.1183; ( b ) J. Burdon, D. R. King, and J. C. Tatlow, ibid., p. 2541.4104302 ORGANIC CHEMISTRYmethanol nucleophile. This argues that the addition of methanol is a step-wise and not a concerted process.247Further examination of substituent effects on the ratio of proton captureto halide ion loss ( l ~ + ~ / k - ~ ) , this time for substituted o-bromophenol anionsin methanol, substantiates the results obtained last year. All substituentsincrease the ( l ~ + ~ / k - ~ ) ratio regardless of the direction of their electronicinteraction, and this is explained, as before, in terms of an aryne-like and ananion-like transition state for halide loss and proton capture, re~pectively.2~~Other investigations have mainly been concerned with new ways ofgenerating arynes.Following up last year's communication on the formationof benzyne in the pyrolytic decomposition of phthalic anhydride (29),249similar intermediates are suspected from the pyrolysis of o-sulphobenzoicanhydride (30) Z5O and several polychlorophthalic a n y h d r i d e ~ , ~ ~ ~ and alsofrom the related electron impact (mass spectrometer) decomposition ofbenzo-2,1,3-selenodiazole (31)-the latter despite its known chemicalstability.252 Full details have also been given of the formation of benzynein the mass-spechral and pyrolytic decomposition of indanetrione (32),253 anda free-radical pathway to benzyne has baen suggested in the decomposition ofo-iodo-N-nitrosoanilides.25* The aprotic diazotisation of 2,5 di-t-butylani-line (33) 255 and o-aminophenylboronic acid 256 both yield products con-sistent with aryne intermediates.The former is believed to react via ahindered carbonium ion (34), which can either lose a proton to give thearyne or react with the s0lvent.2~5247 J. F. Bunnett, D. A. R. Happer, M. Patch, C. Pyun, and H. Takayama, J . Amer.248 J. F. Bunnett and D. A. R. Happer, J . Org. Chem., 1966, 31, 2369.249 E. K. Fields and S. Myerson, Chem. Comm., 1965, 474.250 S.Myerson and E. K. Fields, Chem. Cmm., 1966, 275.251 R. F. C. Brown, D. V. Gardner, J. F. W. McOmie, and R. K. Solly, Chem. Comrn.,Chem. SOC., 1966, 88, 5250.1966, 407.862 N. I?. Buu-Hoi, P. Jacquignon, and M. Mangane, Chem. Comm., 1965, 624.268 R. F. C. Brown and R. K. Solly, Awtra2. J . Chmn., 1966, 19, 1045.264 J. A. Kampmeier and A. B. Rubin, Tetrahedron Letters, 1966,2863; D. L. Brydon266 R. W. Franck and K. Yanagi, Tetrahedron Letters, 1966, 2905.L. Verbit, J. S. Levy, H. Rabitz, and W. Kwalwasser, Tetrahedron Letters, 1966,and J. I. G. Cadogan, Chem. Comm., 1966, 744.1053CHALLIS : REACTION MECHANISMS 303Tetrahalobenzynes have been prepared in several ways, including viathe diazotisation of tetrachloroanthranilic acid,257 the elimination of metalhalides from pentahalophenyl-Grignard and -lithium reagents 258 and, asmentioned above, from the pyrolysis of tetrachlorophthalic anh~dride.2~~In some instances, these arynes show high reactivity in the formation ofDiels-Alder adducts with aromatic substrates : 2580, c, for example, tetra-fluorobenzyne from pentafluorophenyl-lithium will react with thiophen at 25 'to give 40% of 1,2,3,4-tetrafluoronaphthalene. 25&The cycloaddition of benzyne to various aromatic substrates a t hightemperature (690') has also been investigated 259 and the results tentativelyindicate that the ratio of 1,4- to 1,2-addition is 7 : 1;Zs9a at 45", the sameratio is 1 : 4.260 These investigations also suggest that chlorobenzene, itself,may eliminate hydrogen chloride a t high temperatures to form benzyne 259band that the formation of biphenyl from the pyrolysis of benzene involvesphenylcyclohexadiene intermediates.259c Other recent studies have ex-amined the cycloaddition of benzyne to several aromatic dienes 261 andto bicyclobutane.262 The chemistry of arynes has been reviewed agah2G3Homolytic Aromatic Substitution.-Partial rate factors for substi-tution by cyclohexyl radicals (from the decomposition of di-t-butyl peroxidein the presence of cyclohexane) in mono-substituted arenes correlate withHammett a-parameters giving p = +1.1 and it is evident that radicalnucleophilicity decreases in the order cyclohexyl > methyl > phenyl.Theinvocation of trifluoromethyl hyperconjugation (or, perhaps, a, direct field-effect) rather than steric interaction to explain the negligible amount ofortho-substitution in benzotrifluoride is consistent with extensive para-activation (fm = 3-1; fp = 5-0).264 Alkylation has also been examinedfurther with radicals generated by the photolysis of alkyl mercuric iodides :toluene, for example, undergoes about 25% nuclear methylation witho : m : p = 59 : 29 : 12.265 Related studies show that nuclear substituentsbarely influence the rate of a-hydrogen abstraction from alkyl side-chains.266Several investigators have reported on substitution by phenyl radicals.With benzenediazonium fluoroborate in the presence of one equivalent ofpyridine, the partial rate factors for several arenes indicate reaction byphenyl radicals, probably formed via decomposition of an intermediate N -phenylazopyridinium ion :267 in the absence of pyridine, however, phenyla-tion may involve diradical cations.210b Partial rate factors for the Meerwein257 R.Howe, J . Chem. SOC. (C), 1966, 478.t 6 8 ( a ) J. P. N. Brewer and H. Heaney, Tetrahedron letter.^, 1965, 4709; ( b ) D. D.Callander, P. L. Coe, and J. C. Tatlow, Tetrahedron, 1966, 22, 419; ( c ) Chem. Comm.,1966, 143; ( d ) H. Heaney and J. M. Jablonski, Tetrahedron Letters, 1966, 4529.26s ( a ) S . Meyerson and E. I<. Fields, Chem. and Id., 1966, 1230; (a) E. K. Fieldsand S. Meyereon, J. Amer. Chem. SOC., 1966, 88, 3388; (c) ibid., p. 21.280 R. G. Miller and M. Stiles, J . Amer. Chem. SOC., 1963, 85, 1798.281 T.G. Corbett and Q. N. Porter, Austral. J . Chem., 1965, 18, 1781; S. F. Dyke,A. R. Marshall, and J. P. Watson, Tetrahedron, 1966, 22, 2515; R. Muneyuki andH. Tanida, J . Org. Chem., 1966, 31, 1988.263 M. Pomerantz, J . Amer. Chem. SOC., 1966, 88, 5349.a6s R. W. Hoffman, Natumoks., 1965, 52, 656.365 G. E. Corbett and G. H. Williams, J . Chena.. SOC. ( B ) , 1966, 877.268 E. Kalatzis and G. H. Williams, J . Chern. SOC. ( B ) , 1966, 1112.2b7 R. A. Abrsmovitch and J. G. Saha, Tetrahedron, 1965, 21, 3297.J. R. SheIton and C. W. Uzelmeier, J . Amr. Chem. Soc., 1966, 88, 5222304 ORGANIC CHEMISTRYphenylation of biphenyl correlate with localisation energies but not with freevalencies, and the data are discussed in relation to electrophilic isotopic-hydrogen exchange .268 Other investigations have concerned substitution byphenyl radicals in several heterocyclic and bicyclic species 269 includingindene.70Evidence from several sources clearly suggests that photoionisation (withthe ejection of eaq-) is a primary photochemical process for many aromaticcompounds, and the incidence of these reactions has been discussed in detailby Joschek and his co-~orkers.~~6,~71 Aryl radicals resulting from thephotolysis of halogenated compounds react in aqueous solution to form poly-hydroxybenzenes and dihydroxybiphenyls 2 7 l ~ 2 7 ~ or in benzene to yieldbia1yls.2~ Phenoxyphenols produce phenyl and phenoxy-radicals on irradia-tionY27l but other substituted benzenes appear to lose hydrogen from thes u b s t i t ~ e n t .~ ~ ~The reactivities of aryl radicals, measured from the rates of either substi-tution in ~ y r i d i n e , ~ ~ ~ or the abstraction of hydrogen and chlorine fromvarious donor molecules,a75 generally accord with the concept of polarisedradicals in that electron-withdrawing substituents increase the electrophili-city of the radical and vice-versa. There is also evidence, from the thermolysisof phenylazotriphenylmethane , that ground-state solvation in radical formingreactions may be as important as in heterolytic processes.276The isomer distribution ratios for arene substitution by heterocyclicradicals (produced by the photolysis of iodopyridine and iodothiophen) areclosely similar to those for homolytic phenylation.277 Kinetic studies alsoshow that the reaction rates of substituted benzenes and benzoate ions withthe OH radical correlate with Hammett a-constants giving p = -0.41.This suggests that substitution rather than hydrogen abstraction occurs,and the results are discussed in relation to substitution by hydrogen and thesolvated electron.278Although nuclear amination with N-chloramine reagents is thought to bea, heterolytic process in the presence of AlC1, (see page 296), a homolyticexplanation is favoured under redox conditi0ns.2~~ Thus dialkyl-N-chlor-amines with Fe2+ in organic solvents react via amino-radicals, which appear tobe electrophilic giving mainly ortho and para orientation with anis0le.~7~~R,NCl + Fea+ + R,N* + Fes+ + C1-Under acidic conditions, where side-chain chlorination competes with268 S.C. Dickerman, N. Milstein, and J. F. W. McOmie, J . Amer. Chem. SOC., 1965,$7, 6621.26s R. A. Abramovitch and M. Saha, Canad. J . Chem., 1966, 44,1765; H. J. M. DouandB. M. Lynch, Conapt. rend., 1966, 262, C, 1537.270 K. C. Bass and P. Nababsing, J . Chem. SOC. (C), 1966, 2019.2 7 1 H. I. Joschek and S. I. Miller, J . Amer. Chem. SOC., 1966, 88, 3269.872 T. Latowski, E. Latowski, and M. Brudka, Zeszyty Nauk., Mat., Fiz., Chem.,1964, 4, 95; cf. T. Latowski, Roczniki Chem., 1966, 40, 231.27a T. Matsuura and K. Omura, Bull. Chem. SOC. Japan., 1966, 39, 944; cf., N.Kharasch, R. K. Sharma, and H. B. Lewis, Chem. Comm., 1966, 418.274 R. A. Abramovitch and M. Saha, J . Chem. SOC.( B ) , 1966, 733.275 W. A. Pryor, J. T. Echols, and K. Smith, J . Amer. Chm. SOC., 1966, 88, 1189.276 W. G, Bentrude and A. K. MacKnight, Tetrahedron Letters, 1966, 3147.277 L. Benati and M. Tiecco, Boll. sCi. Fac. Chim. kd. Bologna, 1966, 24, 45.278 M. Anbar, D. Myerstah, and P. Netrt, J . Phys. Chem., 1966, 70, 2660CHALLIS : REACTION MECHANISMS 305nuclear amination, it is suggested that radical cations are f0rmed.~7~~* C TheR,NHCl+ + Fez+ --3 R,N+ + Fe3+ + C1-predominance of metu-substitution in toluene and m-xylene is attributed tosteric effects at the ortho-position, and there is evidence of increased side-chain chlorination as the size of the N-chloramine increases:279c however, anentirely different explanation has been advanced to account for meta-orientation under Friedel-Crafts conditions (see page 296.).These studieshave been extended to the amination of na~hthalene,~‘~ biphenyl andfluorene :27gS an interesting reaction with the N-chloro-derivatives of N-methyl-2-phenylethylamine and N-methyl-3-phenylpropylamine under redoxconditions leads to cyclic products (Scheme 9), and an intramolecular addi-tion of the amino-radical cation may be invol~ed.~7~f.CI + H+ + re’+SCHEME 9Following last year’s communication (the first) of a free-radical dis-placement of fluorine from hexafluorobenzene,280 similar displacements havebeen suggested for the photo c y clisation of 3 -pent afluorophenylanthranil(the reagent may be a nitrene, as in the cyclisation reactions of nitroso- andnitro-compounds in the presence of triethyl phosphite 282) and for the photo-catalysed reactions of trichloro- and trimethyl-silane with hexafluorobenzeneto yield mainly C,F,SiFa, and C,F,SiMe,, respectively.283 However, thereaction of SiF, with arenes bears some resemblance to carbene addition:with hexafluorobenzene, 1 : 2 addition followed by rearrangement leads toc,E’,siF3, but complex reactions occur with benzene involving 1 : 4 additionof SiF, p01ymers.~8~Other recent work has disclosed two interesting alternatives to theSandmeyer rea~tion.~g~ In one, direct substitution by halide results whenthe arylamine reacts with pressurised nitric oxide in the presence of cuprichalide catalysts,285b and diazonium ions are likely intermediates.286 There170 (a) F.Minisci, R. Galli, and M. Cecere, Tetrahedron Letter4 1965,4663; F. Minisci,R. Bernardi, L. Grippa, and V. Trabucchi, Chimica e Industria, 1966, 48, 264; ( b ) F.Minisci and R. Galli, Tetrahedron Letters, 1965, 433; (c) F. Minisci, R. Galli, and R.Bernardi, ibid., 1966, 699; ( d ) F. Minisci, V . Trabucchi, R. Galli, and R. Bernardi,Chhica e I%dustrk, 1966, 48, 845; ( e ) F. Minimi, V. Trabucchi, and R. Galli, ibid.,p. 716; (f) F. Minisci and R. Galli, Tetrahedron Letters, 1966, 2531.P. A. Claret, J. Coulson, and G. €3. Williams, Chem. and Ind., 1965, 228.281 P. L. COB, A. E. Jukea, and J. C. Tatlow, J . Chem. SOC. (C), 1966, 2020.288 G. Smolinsky and B. L. Feuer, J . Org. Chem., 1966, 31, 3882.J. M. Birchall, W. M. Daniewski, R.N. Haszeldine, and L. S. Holden, J . Chem.284 P. L. Timms, D. D. Stump, R. A. Kent, and J. L. Margrave, J . Amer. Chem. Soc.,(a) J. I. G. Cadogan, D. A. Roy, and D. M. Smith, J . Chem. SOC. (C), 1966, 1249;SOC., 1965, 6702.1966, 88, 940.( b ) W. Brackman and P. J. Srnit, Rec. Truv. chim., 1966, 85, 857.886 J. Rigaudy and J. C. Vernieres, Cmpt. rend., 1965, 261, 5516306 ORGANIC CHEMISTRYis also defbitive evidence (from e.s.r. spectra) for the formation of phenyl-diazotate radicals (35) from the decomposition of diazohydrides, postulatedas a common intermediate in Reuchardts 287 recent elucidation of homolyticphenylation by the Gomberg reaction and by the decomposition of N-nitro-soacetanilides.288 Consideration of many other interesting aspects of homo-lytic substitution is not possible this year, but the reader's attention is drawnto a recent text289 and to the Gst volume of an annual revie~.~~OC&Cs-N=N-O-N=N-CpH, ---+ CsHS.+ N, + C,H,-N=N-Om(35)Aromatic Rearrangements.-The elusive carbon analogue of the Claisenrearrangement of phenyl allyl ether has finally been realised. Under stronglybasic conditions at 350°, the five isomeric l-phenylbutenes are in thermalc ; s - trans cis- truns3 5 0 4 I ButOKcis-transSCHEME 10equilibrium with the three isomeric l-(o-toly1)propenes in the ratio 93 : 7(Scheme 10) ; isomerisation in the reactants and products arises becausedouble-bond migration in the side-chain is faster than the rearrangementitself. The strongly basic conditions are believed to facilitate re-aroma-tisation of the intermediate allylic triene, although rearrangement via aphenide ion is also considered p0ssible.2~1 Further studies of the thermalrearrangement of aryl allyl sulphides (thio-Claisen) show that the thia-chroman and thiacoumaran products do not readily interconvert under theexperimental conditions.This requires a revised mechanism, possiblyinvolving a thiiran intermediate.292 Other related investigations have con-cerned the formation of 'abnormal' Claisen products from various ethers : 2g3with y-ethylallyl phenyl ether both the normal and the abnormal productsare formed in equilibrium, but the latter is ~redominant.2~~~287 See C. Ruchardt, B. Freudenberg, and E. Merz, Chem. SOC. Special Publ.No. 19,1965, p. 168; C. Ruchardt, Angew. Chem., Internat. Edn., 1965, 4, 964.288 G. Binsch and,&C. Ruchardt, J . Amer. Chem. Soc., 1966, 88, 173.289 W. A. Pryor, Free Radicals," McGraw-Hill, New York, 1966.*90 "Advances in Free Radical Chemistry," Vol. I, ed. Or. H. Williams, Logos2D2 H. Kwart and E. R. Evans, J . Org. Chem., 1966,31,413.z93 (a) R. 33, Roberts and R. G. Landolt, J . Org. Chem., 1966,31,2699; ( b ) A. Jefferson(Academic) Press, London, 1966.E. von E. Doering and R. A. Bragole, Tetrahedron, 1966, 22, 385.and F. Scheinmann, Chem. Comm., 1966,239HOFFMANN : REACTION MECHANISMS 307Isomerisatuion of fluoro- and chloro-t-butylbenzenes 294a and the cor-responding halo-cumenes 294b under Friedel-Crafts conditions results onlyfrom migration of the alkyl groups; for the bromo-derivatives, however,both alkyl groups and bromine atoms migrate as positively charged speciesby intra- and inter-molecular processes.294 The rearrangement of methyl-biphenyls takes place at relatively low temperatures (50”) mainly by 1 : 2methyl- rather than phenyl-shifts as in related compounds.295Recent investigations of the benzidine rearrangement have been con-cerned mainly with the influence of experimental conditions on reaction ratesand product ~ i e l d s .2 ~ ~ Further studies of the acid-catalysed N-nitroaminerearrangement, this time with N-nitro-l-naphthylamines, support earliermechanistic proposals for a direct N-nitro- to C-nitrate shift.2974 This samemechanism, rather than a n-complex or radical-cage alternative, is akofavoured for the related thermal and photolytic rearrangements.297bA recent monograph gives an excellent summary of aromatic rearrange-rnent~.~~8Part (ii) By H.1. R. Hoffmann(Department of Chemistry, University College, Uower Street, London, W.C. 1)SEVERAL books dealing wholly or partly with organic reaction mechanismswere published in late 1965 and 1966.Carbonium Ions. Nucleophilic Substitution at Saturated Carbon.-Following the pioneering work of Meerwein20 a great number of alkoxy-and dialkoxy-carbonium ions has been prepared and identified spectro-scopically. Mass spectrometric appearance potentials as well as spectro-scopic studies in solution confirm the large stabilisation energies 3a of thesespecies 3b (see also Table 1).For example, the gaseous stabilkation energy2*4 ( a ) G. A. Olah, J. C. Lapierre, and U. H. Schreier, J . Org. Chem., 1966, 31, 1268;( b ) G. A. Olah, J. C. Lapierre, and G. J. McDonald, ibid., p. 1262.z96 G. A. Olah and J. C. Lapierre, J . Org. Chem., 1966, 31, 1271.*06 V. &hba and M. VeEei.a, Coll. Czech. Chem. Comm., 1966, 31, 3486; Z. J. Allanand J. RakuBan, ibid., p. 3555; J . Rakugan and Z. J. Allan, Tetvahedron Letters, 1966,4955.297 ( a ) D. V. Banthorpe and J. A. Thomas, J . Chem. SOC., 1965, 7149; (b) ibid.,p. 7158.208 V. A. Koptyug, ‘‘ Isomerisation of Aromatic Compounds,” 0d. N. N. Vorozhtsov,Oldbourne Press, London, 1965.(a) B. Capon, M. J. Perkins, and C. W. Rees, “ Organic Reaction Mechanism1965,” Interscience, London, 1966 ; ( b ) P.D. Bartlet>t, “ Nonclassical Ions,” Benjamin,New York, 1965; (c) P. B. D. de la Mar0 and R. Bolton, “ Electrophilic Additions toUnsaturated Systems,” Elsevier, London, 1966; ( d ) “ Studies on Chemical Structureand Reactivity, Presented to Sir Christopher Ingold,” ed. J. H. Ridd, Methuen, London,1966; ( e ) Progr. Phys. Org. Chem., 1066, 3 ; (f) J. G. Calvert and J. N. Pitts, jun.,“Photochemistry,” Wiley, New York, 1966; (9) N. J. Turro, “Molecular Photo-chemistry,” Benjamin, New York, 1965; (h) R. 0. Kan, “ Organic Photochemistry,”McGraw-Hill, New Yorlr, 1966.a ( a ) R. Criegee, “ The Scientific Work of Hans Meerwein,” Angew. Chem., Internat.Edn., 1966,5,333; see also Chem. Ber., 1967,100, pp.lv-xciv; ( b ) H. Meerwein, “ Metho-den der Organischen Chemie,” Houben-Weyl, Vol. 6/3, Thieme, Stuttgart, 1965, p. 326.(a) Defined as the difference between the appearance potential of CH,+ and+CH,X; ( b ) R. H. Martin and R. W. Taft, J . Anaer. Chem. Soc., 1966, 88, 1353308 ORGANIC CHEMISTRYof (1) is 68 kcal. as compared with 35 kcal. for (2), and successive replacementof the phenyl groups by methoxy-groups in (3) leads to increased 19F n.m.r.shieldings. The latter result confirms the earlier iindings of Meerwein 2b whoshowed that the reaction,Ph,C+ + (MeO),C --+ Ph,COMe + (MeO),C+proceeds to essential completion. Rotation about the C-OMe bonds in(4a) is restricted and requires 11 & 4 kcal./mole of activation energy.Observations on cationR(40: R=H( 4 b : R=CH,)(4b) suggest a higher energy of activation.4 - AR=alkyl or aryl( 5 ) ( 6 )detailed n.m.r.examination of 2-alkyl and 2-aryl substituted dioxoleniumions (5) has3 appeared and dioxolenium ions of sugars have been prepared vianeighbouring acetoxy participation.s The dialkoxycarbonium ion (6) mustbe one of the strongest alkylating agents known so far, since unlike trialkyl-oxonium salts, it alkylates benzophenone, benzaldehyde, and even esters ofhigher carboxylic acids. Other dialkoxycarbonium salts have beendescribed.8a In contrast, solvolytic work on alkoxymethyl derivatives h aremained scarce-an omission, for which the relative reactivity of thesecompounds may be blamed only partly.8bWith the use of Olah's new medium there seems to be almost no limit forstudying carbonium ions a t equilibrium.Stable cycloalkyloxocarboniumions (7), which have been obtained from the corresponding carbonyl halideprecursors,10 show strong absorption around 2200-2500 cm.-l. These ionsas well aa the acyl dications l1 ( 8 ) appear to be useful acylating and diacylatingagents, respectively, for C (in arenes), 0, N, and S. While reaction ofB. G. Ramsey and R. W. Taft, J . Amer. Chem. Soc., 1966, 88, 3058.D. A. Tomalia and H. Hart, Tetrahedron Letters, 1966, 3389; H. Hart and D. A.ti H. Paulsen, W.-P. Trautwein, F. G. Espinosa, and K. Heyns, Tetrahedron Letters,S . Kabuss, Angew. Chem., Internat. Edn., 1966, 5, 675.(a) K. Dimroth and P. Heinrich, Angew. Chem., Internat.Edn., 1966, 5, 676;9 cf. T. Birchall and R. J. Gillespie, Canad. J . Chem., 1965,43,1045; 1964,42,502.Tomalia, &bid., p. 3383.1966, 4131.(a) see also ref. 24, footnote 9.10 GI. A. Olah and M. B. Comisarow, J . Amer. Chem. SOC., 1966,88, 4442.11 G. A. Olah and M. B. Comisarow, J . Amer. Chem. SOC., 1966,88,3313HOFFMANN : EEACTION MECHANISMS 309l-adamantyloxocarbonium hexafluoroantimonate with benzene yields pre-dominantly l-phenyladamantane (with loss of CO), 2-exo-norbornyloxo-carbonium ion acylates benzene without any alkylation.1° The crystalstructure of (9) has been determined and shows the expected linear array ofthe organic moiety.l2The first stable fluorocarbonium ions, phenyldifhorocarbonium ion (10)and diphenylfluorocarbonium ion (11) have been observed by Olah and hisco-workers.13 The large downfield shifts of the 19F n.m.r.of these ionsPhY - FPh(12) (13)relative to their precursors demonstrate appreciable resonance according to(lOa)w(lOb) and recall the comparative stability of singlet difluorocarbenev i s - h i s singlet methylene l 4 (which both have a vacant carbon 2p orbital).The electron-donating ability of fluorine attached to carbonium carbon hasalso been inferred from solvolytic studies on various a-halogenated benzylchlorides.16 Trifluoromethylcarbonium ions (12) have been prepared fromthe corresponding alcohols in FS0,H-SbF5--S0, solution a t low temperature.Bis(triftuoromethy1)methanols (12; R = CF3), on the other hand, do notform bis(trifluoromethy1)carbonium ions.lS The dichlorophenylcarboniumion (13) has been 0bserved.l‘A welcome complement to these studies in solution are the determinationsof &abilisation energies 3a by mass spectrometry 3b (Table 1).While all theTABLE 1 Stabilkation energy (SE) (relative to Car,+) of s+tituted &hq-methyl and halomethgl cations (ref. 3)Ion SE (kcal./mole)CH3+ (0)CH,CH,+ 37 f 3FCH,+ 27 f 3F,CH+ 26 f 3F3C+ 14 & 3ClCH,+ 30 f 4CH,OCH,+ 66 f 385 f 3BrCH, + 37 f 5(CH,O),C + 90 f 3(CH,O) ,CH +l2 F. P. Boer, J . Amer. Chem. SOC., 1966,88, 1572.C. A. Cupas, M. B. Comisarow, and G. A. Oleh, J . Amer. Chem. SOC., 1966,88,361.See, e.g., W. Kirmse, Angew. Chem., Internat. Edn., 1965,4,1; J . Hine, ‘‘ DivalentG. A.Olah and C. U. Pittman, jun., J. Arner. Chem. SOC., 1966, 88, 3310.Carbon,” Ronald Press, New York, 1964; see also ref. 15.l6 G. Kohnstam, D. Routledge, and D. L. H. Williams, Chem. Comm., 1966, 113.l7 H. Volz and W. D. Wyer, Tetrahedron Lettera, 1966, 5249310 ORGANIC CHEMISTBYspecies listed are more stable than methyl cation, ion F3C+ appears to bedestabilised relative to F,CH+ and FCH,+. It is also interesting that there ishardly any additional stabilisation for the (CH,O),C+ cation relative to the(CH,O),CH+ ion. This suggests that '' saturation " has been reached withthe attachment of two methoxy-groups to Ca (see also ref. 91).The benzyl cation cannot be isolated at -60°, since it undergoes rapidpolymerisation at this temperature.17, lS However, a number of poly-alkylated derivatives (14) have been prepared by adding the correspondingbenzyl chlorides to SbF5-S0, solutions l8 a t -75". The supposed prepara-tion of the l-phenethyl cation, which has been retracted,ls provides anotherexample for the potential pitfalls of assigning carbonium ion structures from(14a R=H.R'=CH, or B u t )( I4 b : R = CH, , R = CH,,CH2CI. Br, OCH,) (161U.V. spectral data without supporting n.m.r. evidence. Simple alkylcar-bonium ions like protonated alkyl ketones and trialkylboranes do not absorbin the U.V. above 210 mp.20" The new spectral data for the cations andcarbanions (as measured for the organolithiums) of even and odd alternanthydrocarbons are in reasonable agreement, as expected from simple HMO andSCF-MO considerations.20"Primary aliphatic alcohols (e-g., methanol, ethanol, n-propanol), but alsoisopropyl alcohol can beobserved as the protonated species in FS0,H-SbF,-SO,at -60". The exchange rates of the protons are comparatively slow underthese conditions. 20b N.m.r. spectra for twenty-four cyclopropylcarboniumions have been reported.21 Species (15) is a stable tricarbonium ion. ItsU.V. spectrum suggests only little interaction between the carbonium carboncentres and HMO calculations indicate charge densities similar to the tritylcation.22 The triazidocarbonium ion has been prepared by the route,233SbCl,N, + CCI, -3 [C(N,)3]+SbCl,-l8 C. A. Cupas, M. B. Comisarow, and G. A. Olah, J . Amer. Chem. SOC., 1966,88,362.!ao (a) G.A. Olah, C. U. Pittman, jun., R. Waack, and M. Doran, J . Amer. Chm. Roc.,V. Bertoli and P. H. Plesch, Chem. Cmrn., 1966, 626.1986, 88, 1488; (b) G. A. Olah and E. Namanworth, ibid., p. 5327.T. J. Sekuur and P. Kranenburg, Tetrahedron Letters, 1966, 4769.H. Volz and M. J. Vole de Lecea, Tetrahedron Lettera, 1966, 4676, 4683.ta U. Miiller and K. Dehnicke, Aragew. Chern., Internat. Edn., 1966, 5, 841HOFFMANN : REACTION MECHANISMS 311Solvolysis of optically active phenylbiphenyl-cc-naphthylmethyl benzoatein aqueous acetone and dioxan entails high net retention of configuration.24It has been suggested that the observed stereoselectivity results from solventcapture of the free carbonium ion (16), which can be asymmetric because thenaphthalene nucleus does not lie in the same place as the two other aromaticgroups and rotation is restricted. Murr and Santiago's work presents thechallenge to isolate such optically active carbonium ions, carbanions, andradicals.The pentachloroallyl cation (17) (prepared from hexachloropropene andaluminium trichloride) appears to be less stable 25a than the trichloro-cyclopropenyl cation ( 18) (obtained from tetrachlorocyclopropene andaluminium trichloride) .2Sb Kuhn and Sondermann 26 have reported bothCl(17) (18)[Ar-CH-(CH=CH),-Ar]+BF,- (n = 0-4)(19)experimental and theoretical studies of the polyenyl cations (19).Penta-dienyl cations can be observed readily in FS0,H-SbF, at low temperaturesand there is the prospect that the stereochemical course of the consecutivering-closure to cyclopentenyl cation may soon be el~cidated.~' The depen-dence of conformational and isomer stability on the number of electrons inextended n-systems has been discussed by Hoffmann and Olofson.28All four epimeric thuj yl toluene-p-sulphonates (20) rearrange extensivelyin 96% sulphuric acid yielding, however, one final product (21) 0nly.2~The homocyclopropenyl cation (22) has also been prepared.30A number of stable aliphatic diazonium cations RN2+, in which the non-terminal nitrogen atom is attached to sp2 hybridised carbon have been(21) (22) (201SCHEME 124 B.L. Murr and C. Santiago, J . Amer. Chem. Soc.: 1966, 88, 1826.25 (a) R. West and P. T. Kwitowski, J . Amer. Chem. SOC., 1966,88,5280; ( b ) R.West,26 J. Sondermann and H. Kuhn, Chem. Ber., 1966, 99, 2491. *' C. A. Olah, C. U. Pittman, jun., and T. S. Sorenson, J . Amer. Chem. Soc., 1966,28 R. Hoffmann and R. A. Olofson, J . Amer. Chem. SOC., 1966, 88, 943.2Q S . Forsen and T. Norin, Tetrahedron Letters, 1966, 4283.30 E. H. Cold and T. J. Katz, J . Org. Chem., 1966, 31, 372.A. SadB, and S. W. Tobey, ibid., p. 2488.88, 233312 ORGANIC CHEMISTRYdescribed.31 A preparative use of carbonium ions consists of their electro-philic addition to 1 ,l-dichloroethylene (Scheme 1) yielding substitutedpropionic acids.32The carbonylation of carbonium ions (Koch synthesis) :R+ + CO + RCO+has been reviewed 33 and extended to the preparation of secondary carboxylicacib.34, The deaminative formation of carbonium ions by the routes:has also been described.34bThe cyclobufadienyliron tricarbonyl methyl carbinyl cation has beenprepared as the hexachloroantimonate salt.The proton H, appears atlowest field (~3.48, sinslet) and it has been suggested 35 that this particularfeature favours formulation (23) over (24). For the ferrocenylcarbonium ion(25) there is disagreement between Richards and co-w~rkers,~~ who originallysuggested metal participation as in (25b), and Traylor 37a and Rosenblum 37b(23)GyHR FcHwho prefer structure (25a) with an exocyclic double bond. Whatever theMooberry, and P. Y. Johnson, J . Amer. Chem. SOC., 1966,88, 4288.s1 K. Bott, Tetrahedron, 1966, 22, 1251; see also P. Beak, R. 5. Trancik, J. B.K. Bott, Angew. Chem., Internat. Bh., 1965, 4, 956; K. Bott and H. Hellmann,33 Y. Mayor, Ind. chim. belge., 1966, 53, 213.s4 W. Hartf, Chem. Ber., 1966, 99, 1149; (b) 0. A. Olah, N. Friedman, J. M. Bol-lhger, and J. Lukas, J . Amer. Chem. SOC., 1966, 88, 5328.36 J. D. Fitzpatrick, L. Watts, and R. Pettit, Tetrahedron Letters, 1966, 1299.m M. Cais, J. J. Dannenberg, A. Ekemtadt, M. I. Levenstein, and J. H. Richards,Tetrahedron Letters, 1966, 1695; see also A. N. Nesmeyanov, E. G. Perevalova, S. P.Uubin, K. I. Grandberg, and A. G. Kozlovaky, ibid., p. 2381.8' (a) T. T. Tidwell aad T. G. Traylor, J . Amer. Chem. SOC., 1966, 88, 3442; ( b ) M.Roeenblum and F. W. Abbate, ibid., p. 4178.w., 1966, B, 870HOFFMANN : REACTION MECHANISMS 313better description, it would appear that the contested dserence is subtle andcan only be detected by determining the crystal structure of, say, the hexa-chloroantimonate salt.The ion C8H,+ from protonation of cyclo-octatetraene (26) is the 6n 7cmonohomotropylium ion (27a).38 The large chemical shift (5.8 p.p.m.)between the highfield ‘‘ inside ” proton (27 ; X = H) and the outside protonrules out the suggested 39 cyclopropylcarbonium ion formulation (29).38Likewise, the position of ultraviolet maxima and HMO calculations supportstructure (27a).380 Deuteration with D,SO, of (26) at -10” is stereoselectivewith 80% of the deuterium “inside” (27b). If the equilibration(27b) + (27c) is visualised to proceed by ring inversion through the classicalX vH(20) (27a:X =H 1(27b: X=D)planar cyclo-octatrienyl cation (28), then the free energy of (28) is 22.3kcal./mole above that of the homoaromatic counterpart (27).a8a At lowtemperature the chlorination and bromination of (26) are also stereospecific,yielding exclusively the bicyclic valence tautomer (30) with cisoid halogens.40At the time of writing no mechanistic interpretation of these facts hadappeared.An excellent commentary and collection of reprints I* on nonch8icubcarbonium iana and three (!) further reviews 41 (Sargent’s 41a pro andBrown’s 41b contra) have been published. In an important reinvestigation ofthe n.m.r. spectrum of the stable norbornyl cation in liquid sulphur dioxidea t -80” Jensen and Beck 42a have now observed fine structure due to spin-spin splitting. Their results are not consistent with the classical ion (31)38 ( a ) S. Winstein, C. G. Kreiter, and J. I. Brauman, J . Amer. Chem. SOC., 1966,88, 2047; ( b ) C. E. Keller and R. Pettit, ibid., pp. 604, 606.39 N. C. Deno, Progr. Phys. Org. Chem., 1964, 2, 157.R. Huisgen, G. Boche, W. Hechtl, and H. Huber, Angew. Chem., Internat. Edn.,1966, 5, 585; R. Huisgen and G. Boche, Tetrahedron. Letters, 1965, 1769.41 ( a ) G. D. Sargent, Quart. Rev., 1966, 20, 299; ( b ) H. C. Brown, Chem. Brit.,1966, 199; see also H. C. Brown and G. L. TritIe, J . Amer. Chem. SOC., 1966, 88, 1320;(c) Q. E. Gream, Rev. Pure Appl. Chem. (Australia), 1966, 16, 25.ra (a) F. R. Jensen and B. H. Beck, Tetrahedron Letters, 1966,4287; ( b ) M. SaundersP. von R. Schleyer, and G. A. Olah, J . Arner. Chem. Soc., 1964, 80, 5680314 ORGANIC CIHEMISTRYtibeing the stable species under the cited conditions. However, it has beensuggested that 3,a-hydride shifts (which had been known to proceedslowly 42b) do involve classical ions, which are present in low concentrationwith more stable nonclassical species. Most likely, these nonclassical ions areeither stable alkyl-bridged (33a-c) and hydrogen-bridged (32a-c) ions oralternatively, the alkyl-bridged ions, while edge-protonated cyclopropanes(32a-c) serve merely as transition state~.~20The situation regarding a number of substituted norbornyl cationsremains to be clarified. While a 2-methoxy-substituent produces the trulyclassical 2-methoxynorbornyl cation 43a (a fact which is not surprising inview of what was said above about alkoxycarbonium ions), Brown andRei 48b have further urged the adoption of the classical description for thetertiary 2-methylnorbornyl cation. Acid-catalysed equilibration (with1-75~x-perchloric acid in 60% aqueous dioxan) of the 2-methylnorbornanolsindicates that the ground-state energies for the ex0 and endo tertiary isomersare approximately equal under the cited conditions, and it has been con-cluded that the observed high exo : endo ratios (in the solvolysis of Z-methyl-norbornyl derivatives) cannot result from a fortuitous cancellation of in-creasing steric assistance with decreasing nonclassical participation by the1,6-electron pair, as had been suggested by von Schleyer.The rate retardation by C-6 substituents in exo-norbornyl solvolyses 44ahas been further investigated by Berson and collaborators.44b These authorshave studied the microscopic reverse to the solvolysis of (34) and haveagreed that a steric effect (presumably nonbonding repulsion) specific to thetransition state (35) accounts for part of the observed rate retardati~n. etc etc.Various Compounds Derived from Phenylalanine and Tyrosine.-Grisebachand his colleagues have continued their studies on flavanoid biosynthesis.The tritiated dihydroflavonol, dihydrokaempferol (89), was transformed inbuckwheat seedlings into quercetin (90) and cyanidin. [ l-14C]Phenylalaninewas mixed with the tritiated precursor to serve as an internal standard formeasuring incorporations.76 Insignificant incorporation into isoflavones,for example biochanin A (91), was observed.77 However, the optically-active flavanone (92) was incorporated into both quercetin (90) and bio-71B. Franck, F. Huper, D. GrGger, and D. Erge, Angew. Chem. Internat. Edn.,1966, 5, 728.J. W. Apsimon, J. A. Corran, N. G. Creasey, W. Marlow, W. B. Whalley, and(in part) K. Y. Sim, J . Chem. Soc., 1966, 4144.73 U. Sankawa, H. Taguchi, Y. Ogihara, and S. Shibata, Tetrahedron Letters, 1966,2883.7* R. D. Hill, A. M. Unrau, and D. T. Canvin, Canad. J. Chem., 1966, 44,2077.V s E. Leete, “Biogenesis of Natural Products”, ed. P. Bernfeld, Pergctmon Pres8,Oxford, 1963, p. 752.713 W. Barz, L. Patschke, and H. Grisebach, Ckem. Comm., 1965, 400; L. Patschke,W. Barz, and H. Grisebach, 2. Naturforsch., 1966, Zlb, 45; see also W. Barz and H.Grisebach, ibid., p. 1113.7 7 W. Barz and H. Grisebach, 2. Naturforsch., 1966, Zlb, 47; cf., H. Imaeeki, R. E.Wheeler, and T. A. Geissman, Tetrahedron Letters, 1965, 1785KIRBY: BIOSYNTHESIS 575chanin A (91) much more efficiently than its enantiomer.'S The smallincorporation of the " wrong " enantiomer may have resulted from race-misation via the chalcone (93; R = OH). Wong and Moustafa 79 found thatisoliquiritigenin (93 ; R = H) was converted by a crude enzyme system fromsoybean seedlings into the corresponding optically active flavanone, liquiriti-genin [configuration as in (92)]. Incorporation of the glucoside (94) intoskimmin (95) in Hydrangea mcrophylla has been studied.80 The precursorwas labelled with 14C both at C-2 and, uniformly, in the glucose residue. Itwas found that the ratio of activities in the coumarin and glucose moietiesof skimmin varied with the time allowed for metabolism. The authorsdiscuss the difficulties sometimes encountered in interpreting results fromexperiments with multiply labelled precursors. The beetle, Eleodes Zongi-coZZis, produces several benzoquinones (96; R = H, Me, or Et).sl Tyrosineand phenylalanine were incorporated into benzoquinone itself but not intothe methyl and ethyl derivatives. It was shown that the substitutedquinones were derived from acetate, propionate, and malonate, prtmrnablyby the usual polyketide pathway. For example, [1-l4C]propionate gaveethyl-benzoquinone labelled as shown (96; R = Et). [15N,U-14C] Tyrosinewas converted by Sorghum vuZgare into the glucoside, dhurrin (97; R = H,R' = Glu.), with retention of nitrogen.S2. Tyrosine was also a precursor forthe isomeric cyanohydrin (97; R = Glu., R' = H).8s Experiments withNasturtium oflcinale have shown84 that conversion of the homologue ofphenylalanine, L-y-phenylbutyrine (98), into gluconasturtiin (99) occurs withretention of nitrogen. Similarly, 14C and 15N labelled specimens of homo-methionine (100) have been used to demonstrate intact incorporation intosinigrin (101) in Armoracia Z~pathifolia.~~ Tyrosine provides the aromaticC6--C2 unit of the modd metabolite, anisomycin (102),s6 and S-dimethyl-amino-3-phenylpropanoic acid is formed in the yew tree from phenylala-nine.87M. Matsuo and M. Yamazaki, Biochem. and Biophyt?. Rear. Cmm., 1966, 24, 786.86 K. Butler, J. Org. Chem., 1966, 31, 317. *' E. Leete and G. B. Bodem, Tetrahedron Letters, 1966, 3926