4 Reaction Mechanisms Part (ii) Polar Reactions By D. G. MORRIS Department of Chemistry University of Glasgow Glasgow G12 8QQ 1 Introduction In the present Report there are sections on substitution on which much relevant work has appeared eliminations ester hydrolyses micellar reactions and miscel- laneous topics. A review entitled ‘How does a reaction choose its mechanism?’ has appeared’ and other relevant reviews include ‘Enolisation of simple carbonyl compounds’,* ‘Degenerate Carbocation rearrangements’,’ and ‘Mechanisms of nitro~ation’.~ 2 Substitution Reactions At very low concentrations (5 x 10-3moldm-3) in benzene (1) is transformed into (2) by an intramolecular endocyclic SNmechanism to the extent of 16%;the balance of the reaction is made up of an intermolecular component.’ The proportion of intramolecular reaction decreased regularly with increase in the initial concentra- tion of (1).In the case of the lower homologue (3) however the reaction was intermolecular at all concentrations.The authors note that the intramolecular substitution undergone by (1)defines a minimum ring-size for the transition state in this type of process as nine Nucleophilic attack on sp2 and sp3 hybridized carbon by pyridines and imidazoles between 0-2 a-methyl groups has been examined6 in the light of a theory that ‘conesof trajectory’ are permitted for most reactions with each trajectory associated with a particular degree of formation and of cleavage of bonds. A single methyl produced a relatively minor retardation of the reaction whereas a second methyl W.P. Jencks Chem. SOC.Rev. 1981,10 345. ’J. Toullec Adv. Phys. Org. Chem. 1982 18 1. P.Ahlberg G. Jonsell and C. Engdahl Adv. Phys. Org. Chem. 1983,19 223. ‘D.L.H. Williams Ado. Phys. Org. Chem. 1983 19 381. ’J. F.King and M.J. McGarrity J. Chem. SOC.,Chem. Commun. 1982,175. F. M. Menger and D. Y. Williams Tetrahedron Lett. 1982,23,3879. D. G. Morris was much more effective in accord with expectations based on a fairly wide angular window for reaction. The observed changes had their origins principally in AHf effects. In the synthesis of dl-coriolin A the transformation of (4) into (5)with potassium superoxide under the conditions indicated proceeded in over 82% yield at the neopentylic position.7 (i) 5 equiv.dibenzo-18-crown-6 ether _____) DMSO DME at r.t. for 48 h H (ii) H,O NaBH H The first unambiguous SN2reaction at a cyclopropane carbon was observed in the conversion of (6)into (7) by Bu'OK in dimethyl sulphoxide.8 CI Rate constants for displacements of exo-and endo-2-norbornyl brosylate by azide ion in toluene are ~imilar.~ Substantial though not excessive steric congestion is indicated by the fact that these substrates react ca 500 times faster than the seriously encumbered 2-adamantyl brosylate. By means of a rapid-injection n.m.r. technique in 95% aqueous CF,COOD and in the temperature range 5-65 "C it was found that CF3S03- is a better leaving group from MeOS02CF3 than is dimethyl ether from Me,O' BF4- when allowance is made for the statistical factor of three in the latter case." Pyramidal inversion at three-co-ordinate nitrogen and inversion of configuration at saturated carbon respond inversely to substituent and angular-constraint effects." In particular the enhancement of rate that is brought about by introduction of an a-carbony1 substituent is related to the presence of a stabilizing orbital interaction 'of a new type' in the transition state.From application of a configuration-mixing model it was found that the extent of development of charge in an SN2transition state is not a function of the position of the transition state along the reaction co-ordinate. l2 'F. Ito N.Tomiyoshi K. Nakamura S. Azuma M. Izawa F. Marnyama M. Yanagiya H. Shirahama and T.Matsumoto Tetrahedron Lett. 1982,23 1721. * L. A. M. Turkenburg W. H. de Wolf F. Bickelhaupt C. H. Stam and M. Koniju J. Am. Chem. Soc. 1982,104,3471. K. Bauert and W. Kirmse J. Am. Chem. SOC.,1982,104,3766. lo J. F. McGarrity and J. W. Prodolliet Tetrahedron Lett. 1982 23 417. S. Wolfe D. J. Mitchell and H. B. Schlegel Can. J. Chem. 1982 60 1291. l2 A. Pross and S. S. Shaik Tetrahedron Lett. 1982,23. 5467. Reaction Mechanisms -Part (ii) Polar Reactions The activation barrier for sN2 reactions in the gaseous phase has been attributed to an avoided crossing of two curves which contain the reactant- and product-like Heitler-London valence-bond forms R=R=X and N=R=X-.l3 The reaction barrier was shown to be a fraction 3f the energy gap (IN:-A& where IN:equals the ionization energy of the nucleophile and ARXis the electron affinity of the substrate.The size of the fraction depends on the slopes of the two curves which in turn are influenced by inter alia the extent of delocalization of three-electron- bonds and differences in strength between C-X and N-C. In the reaction between para-substituted benzyl chlorides and 3Ar electron- withdrawing substituents in the chloromethyl-bonded aromatic ring lead to a transition state with a shorter S--C bond and less conjugation between the aromatic ring and the a-carbon.14 When conjugation is important in the transition state the secondary a-deuterium kinetic isotope effects are appreciably lower. U-shaped Hammett plots in these reactions have been attributed to a variation in the importance of resonance and polar effects rather than to a change in mechanism.McLennan and Martin15 have noted that multiple equilibria involving the solvent accompany substitution processes at saturated carbon in solution; thus the observa- tion of curved Arrhenius plots is in order. Accordingly attempts to rationalize this behaviour in terms of ion-pair return in all cases are ill-advised. The s01id-state'~C n.m.r. spectrum of the 2-norbornyl cation has been determined in the range 77-200 K using cross-polarization magic-angle spinning.'6 Although the results 'do not remove contentious issues' no evidence was adduced for a classical norbornyl cation; from analysis of the lineshapes of a chemical exchange process that was observed in the solid state the value E = 5.9 f0.2 kcal mol-' was found for the 6,1,2 hydride shift.If the norbornyl cation is classical then the barrier for degenerate Wagner-Meerwein rearrangement is <ca 3 kcal mol-'. At O'C in methylene chloride in the presence of TiC14-HCI for 8 hours the [2.2]paracyclophanes (8) and (9) were converted into (lo) which was stable to the (8) R' = R2 = Me,R3 = H (10) R = Me (9) R' = R3 = Me,R2 = H l3 S. S. Shaik and A. Pross,J. Am. Chem. SOC.,1982 104 2708. l4 K. C. Westaway and Z. Waszczylo Can. J. Chem. 1982,60,2500. D. J. McLennan and P. L. Martin J. Chem. SOC.,Perkin Trans. 2 1982 1099. C. S. Yannoni V. Macho and P. C. Myhre. J. Am. Chem. SOC.,1982,104,907. D.G. Morris reaction conditions. ' ' The reaction proceeds by way of intramolecular migration of a methyl group from one deck of the paracyclophane to the other. The key steps the methyl migrations are exemplified when (8)is the starting material by the conversion of (11)into (12). In this instance (12) was not directly observable although evidence for its intermediacy was obtained when the initial substrate was (9). The first example of a 1,2 intramolecular migration of a -COOH group towards an electron-deficient centre has been reported,'' occurring as a consequence of the subjection of PhCH(OH)CMe,COOH that is doubly labelled with 13C at C-1 and C-3 to HS03F and SO2C1F (1:3) at -100 "C followed by warming to 0 "C. The preference for migration of COOH to give PhC(COOH)=CMe, is accounted for on the basis of the stability of the carbo-cation precursor.At -2O"C in the presence of AgSbF6 in benzene-methylene chloride the a-bromo-ketone (13) gave mainly (i.e. >95%) (14) whose formation was rationalized in terms of the highly stereoselective cyclopropylmethyl-cyclopropyl-methyl rearrangement that is depicted in Scheme l.19 H +,-COPh /O PhH D-yH-C,, -Ir -PhCH2 Br H'A'Coph H (13) (14) Scheme 1 The pentamethoxyallyl cation (16) which has been generated from (15) under a variety of conditions at -30 "C shows variable-temperature n.m.r. spectra. These have been attributed to equilibration of inner and outer terminal methoxy-groups brought about by rapid rotation around the C-1-C-2 (or C-2-C-3) bonds; this process is associated with AGS = 11kcal mo1-'.20 Me0 OMe OMe MeOyOMe CI OMe (15) (16) The major (>8O%) product that is formed from hydrolysis of either the cyclopro- pylcarbinyl (17) or the homoallyl (18) derivatives was the alcohol (19).2' The enhancement of rate that is associated with the formation of the purported carbo- cation intermediate (20) is 2 x lo4with respect to the 4-homoadamantyl analogue (21); that for (22) is very high i.e.3 x lo' for an asymmetric double-bond with respect to the epimer (23). The ratio of rate constants of (23) in which participation of a double bond is precluded to (21) uiz 0.1 provides the best estimate yet of the inductive destabilization of a developing carbo-cation centre by a homoallylic double-bond.J. Kleinschroth S. El-tamany and H. Hopf TetrahedronLert. 1982 23 3345. D. Berner D. P. Cox and H. Dahn J. Am. Chem. SOC.,1982,104 2631. l9 C. Pardo and M. Charpentier-Morize J. Chem. SOC.,Chem. Commun. 1982 1037. 'O R. A. Moss W. Guo A. Hagedorn and R. Beveridge J. Chem. SOC.,Chem. Commun. 1982 1102. " J. M. Harris J. R. Moffatt M. G. Case F. W. Clarke J. S. Polley T. K. Morgan T. M. Ford and R. K. Murray J. Org. Chem. 1982,47,2740. Reaction Mechanisms -Part (ii) Polar Reactions (17) X = DNB (18) X = C1,Y = H (20) (19) X = H (22) X = OTs,Y = H (23) X = H,Y = OTs The similarity of the 13C n.m.r. spectra of the 2-hydroxytropylium ion (24) in the solid state and in solution in methylene chloride indicates that there are no substantial differences in structure or in distribution of charge.*' X-Ray crystal structure analysis has revealed a shallow boat for the seven-membered component of this ring with the 'bridging' C-8 carbon held over the ring.The C-1-C-7 separation [1.626(8) A] is greater than that for a free cyclopropane ring (1.510 A) whereas the C-1-C-8 bond [1.488(7) A] is shorter; the respective lengthening and shortening of these bonds is in accord with delocalization which affects only the internal 'cyclopropane' bond. Direct observation of the special salt effect originally proposed on the basis of kinetic analysis of acetolyses of sulphonate esters has been provided by analysis of the photoreduction of benzophenone by NN-diethylaniline in acetonitrile in the presence of NaC104.Irradiation in the absence of salt gave after rapid electron transfer a solvent-separated ion-pair within 300 ps; after diffusion together a contact ion-pair whose components were the amine radical cation and a benzo- phenone radical anion was formed. In the time interval between 500 ps and 10ns A,, shifts to 645 nm in the presence of sodium perchlorate to give a sodium contact ion-pair with a rate which depends on [NaC104].23 The limiting rate of formation of this ion-pair was determined by photolysis of (25) which is so constructed that the methylene bridge precludes formation of an amine contact ion-pair although a charge-transfer intermediate analogous to an amine-solvent-separated ion-pair is formed initially.Rate constants for formation of the sodium contact ion-pair are 7.2 x 108mol-'s-' for both (25) and NN-diethylaniline; this accords with the conclusion that NaC104 intercepts both the inter- and intra-molecular systems at the same stage namely the solvent-separated ion-pair. A somewhat smaller rate constant that was observed for (25) and NaI has been attributed to the need to effect solvent separation of the component inorganic ions. 22 R. F. Childs A. Varadajan C. J. L. Lock,R. Faggiani C. A. Fyfe and R. E. Wasylishen J. Am. Chem. SOC.,1982,104,2452. 23 J. D. Simon and K. S. Peters 1.Am. Chem. SOC.,1982 104,6142. D. G.Morris The specific rates for solvolysis of (26) respond to changes in the solvent in the same way inter afia,as exo-norbornyl tosylate; accordingly (26)is taken to solvolyse via a kAprocess with assistance provided by the strained carbon-carbon bond in common with the lower cyclopropylcarbinyl hom01ogue.~~ However cyclopentyl- methyl brosylate reacts by way of competitive kA and k processes whose ratio varies with nucleophilicity of the solvent In the weakly nucleophilic solvents formic acid trifluoroethanol and hexafluoroisopropyl alcohol there is a significant increase in 1,3-shift of hydride during the solvolysis of (27) as the nucleophilicity of the solvent decrease^.^' No detectable (<O.S0/o) 1,3-shift of hydride was observed in the case of (28) in which there is no tertiary carbo-cation to provide a driving force; this work clarifies earlier cited reports.TsO@R2 R' (27) R' = H R2.= Me (28) R' = D,R2 = H Attribution of lower a-deuterium kinetic isotope effects than the limiting value of ca 1.22 to steric effects in the initial state during the solvolyses of 1-(1-adamanty1)ethyl sulphonates prompted a more detailed investigation; this revealed in particular that the lowest a-D kinetic isotope effect i.e.1.111 in 97% CF3CH,0H-3 O/O H20 corresponds to the greatest proportion of substitution with rearrangement.26 A rearranged or partially rearranged transition-state structure is proposed. It is calculated that replacement of the oxygen of the leaving group by a transition-state bond to carbon would lead to an a-D kinetic isotope effect of ca 1.07. Conversion of [1-'*0,8,9-14C]geranyl pyrophosphate (29) into d-bornyl pyrophosphate (30)by the enzyme system from Salvia officinalis was effected with essentially no positional exchange of oxygen isotope; 32Plabelling indicated that two ends of the pyrophosphate do not become equivalent during this interconver- ion.'^ The very tight restriction on the motion of the transiently generated inorganic pyrophosphate is unexpected.The mechanism is indicated in Scheme 2. The same precursor (29) was converted into the enantiomeric 1-bornyl pyrophosphate by the supernatant of whole leaf homogenates in Tanacetum vulgare. 24 D. D. Roberts J. Org. Chem. 1982,47 561. 25 H.-J. Scheider and R. Busch J. Org. Chem. 1982.47 1766. 26 V. J. Shiner T. E. Neumann and R. D. Fisher J. Am. Chem. SOC.,1982,104,354.*' D. E. Cane A. Saito R. Croteau J. Shaskus and M. Felton J. Am. Chem. SOC.,1982 104 5831. Reaction Mechanisms -Part (ii) Polar Reactions (30) Scheme 2 The question of whether the nortricyclylcarbinyl cation (3 1) has an enhanced vinyl-bridged 2-norbornyl character (32) has been addressed by both MIND0 and STO-3G calculations; these methods indicate an enhanced contribution of (32) to the structure with respect to the simple unbridged case. Experimental methods were indecisive in assessing the relative weighting of (31) and (32) to the stru~ture.~~*~~ 3 Elimination Reactions Solvolyses of 1-[*Hl]cyclo-octyl brosylate in a variety of solvents have shown that elimination is favoured from the C-1 site rather than from C-5 by a factor of 1.5 to 3.2.30 This indicates that a tightly paired counter-ion is the principal base in the E 1 reaction leading to cyclo-octene; there is appreciably less preference between the two sites in substitution reactions which take place via more dissociated intermediates.*' L. R. Schrnitz and T. S. Sorensen J; Am. Chem. SOC.,1982,104 2605. 29 L. R.Schmitz and T. S. Sorensen J. Am. Chem. SOC.,1982,104,2601. 30 J. E. Nordlander P. Ownor D. J. Cabral and J. E. Haky J. Am. Chem. SOC.,1982,104 201. D. G.Morris In the conversion of (33) into (36) the Elcb mechanism shown in Scheme 3 was propo~ed,~' in which deprotonation is not rate-determining; (34) and (35) gave the diene at least lo3 times faster than did (33).The increased rate of elimination brought about by relief of ring strain is estimated to be >lo" by comparison with acyclic analogues.S02Ph ,S02Ph ,S02Ph S02Ph PhS02-PhSOl Scheme 3 The same group3' noted that carbon leaving groups (i.e.those in which the leaving group is bonded to C through carbon) exhibit very low nucleofugality in elimination reactions; thus the formation of (38)from (37) as shown in Scheme 4 is associated with kobs= 1.5 x 10-9dm3mol-1s-'. EtOH A PhS02 N 0 2 +'OEt PhSOz (37) 1 )-NO2 + PhS02- (38) Scheme 4 With (39),an enhancement of kobsby 4 X 10" is observed and for this substrate in which incorporation of the leaving group into a cyclopropane ring has generated an excellent nucleofuge the mechanism is now E2 rather than Elcb.@& \ / PhSO,aNO' H27 NMe3 (39) MeOMe (40) 3' G. Griffiths S. Hughes and C. J. M. Stirling J. Chem. SOC..Chem. Commun. 1982 236. 32 P. P. Piras P. J. Thomas. and C. J. M. Stirling J. Chem. Soc. Chem. Commun. 1982 658. Reaction Mechanisms -Part (ii) Polar Reactions At 50.6"C in chloroform alkene is formed exclusively from (40) with a rate constant kl = 128 x 10-3s-'. The driving force for this El mechanism support for which is provided by Hammett p values and p deuterium kinetic isotope effects is relief of a steric interaction between the relatively poor leaving group and the ortho substituents of the benzyl group.33 By means of a qualitative valence-bond method the E2C-E2H mechanistic spectrum of elimination reactions has been j~stified.~~ The authors claim that the E2C transition state is 'looser' with respect to B-C approach (B = base) and hence less sensitive to steric influences than the tighter sN2 transition state.Accor- dingly a cited test case which provided evidence against the E2C mechanism is not considered appropriate. Nevertheless rate constants for bimolecular elimination of cyclohexyl bromide with thiophenoxide naphthoxide carbazole and fluorene nitranions were com- pared at the same basicity by means of Bronsted correlation^^^ and found to give a markedly different sequence to that exhibited for sN2 reactions. In particular oxanions and nitranions promote elimination much more readily whereas S,2 reactions are favoured much more by carbanions.Apparent correlations previously observed between SN2and E2 rate constants are considered to be fortuitous and the authors3' consider that 'there is no reason to believe that in some E2 transition states the anion is bonded to carbon as well as to hydrogen'. This study does not concern itself with bromide the archetypal E2C reagent however. Pross and Shaik34 have also proposed a mechanism for elimination depicted in Scheme 5 in which an electron is transferred from B to the C-X moiety leading to (41)and thence to olefin. I \ -C-C/ \> -+ H-BB+ + ,C=C + X-I X- Scheme 5 4 Ester Hydrolyses and Related Reactions The stereochemistries of methanolyses of phenyl phosphate monoanion (pK of the leaving group is 9.9) and of 2,4-dinitrophenylphosphatedianion (pK of the leaving group 4.1) have been investigated with both phosphates labelled as R-[l60 I7O '*O],in the light of the mechanism shown in Scheme 6.36Both reactions R-0-PO3H-$ R-6-P032-+ ROH + PO3-I H 1 H2PO4-Scheme 6 33 J.Pradham and P. J. Smith Tetrahedron Lett. 1982,23 611. 34 A. Pross and S. S. Shaik J. Am. Chem.SOC.,1982 104 187. 35 F. G. Bordwell and S. R. Mrozack J. Urg. Chem. 1982,47,4813. 36 S. L. Buchwald and J. R. Knowles J. Am. Chem. Soc. 1982. 104. 1438. D. G.Morris proceed with complete inversion of configuration at phosphorus. The results require that if metaphosphate forms it is not symmetrically solvated but is captured exclusively by nucleophilic attack from the side opposite to the leaving group.A pre-associative mechanism involving (42),where A is a nucleophilic acceptor is also feasible. Staphylococcal nuclease catalyses the hydrolysis of one of the diastereoisomers of thymidine 5'-(4-r1itrophenyl)['~O,~*O]phosphate in isotopically normal water to yield 4-nitr0phenyl['~O,'~O,~~O]phosphate with inversion of configuration at phosphorus (Scheme 7).37The most probable mechanism involves direct attack of water on phosphorus general-base-catalysed by glutamate with displacement of thymidine (which is the poorer leaving group) taking place. 170 170 180. I 02N~o~P-ovThy H2'hO) I OH Scheme 7 Hydrolysis of (43)takes place via allylic substitution under specific conditions to give (44),as shown in Scheme 8.38 H C02Ar2 H C02Ar2 \/ \ -/ -HO-C-C Ar' ,c=c \CN Ar '/ 'CN C02H 1 / HO-CH-CH HO-CH-C=C=O I I Ar' 'CN Ar' &bJ Ar'= O O M e H c02-\/ c=c Ar I/ 'CN (44) Scheme 8 37 S.Mehdi and J. A. Gerit J. Am. Chem. Soc. 1982,104 3223. '' M. Inoue and T. C. Bruice J. Am. Chem. SOC., 1982 104 1644. Reaction Mechanisms -Part (ii) Polar Reactions In the pH range 8-12 the rate constant for the hydrolysis of ester (45) shows a plateau and the reaction is characteri~ed~~ by a rate-determining unimolecular decomposition of the conjugate base (46)in a process with AS' = +40 kJ mol-' K-'. This dissociative mechanism thus operates in a carboxylic ester that is devoid of a-protons and is mediated by the para-oxoketen (47). OH 0-8CO Ar product CII 0 (47) Scheme 9 In aqueous acetonitrile acid-catalysed hydrolysis of inter alia (48) is a minimum at 20-25 mol dm-3 water; the rate increases at lower concentrations in contrast to that of the corresponding carboxamide.Nucleophilic catalysis was shown not to be imp~rtant.~' The mechanism shown in Scheme 10 (in which S is H20or MeCN) 0 OH--S I1 +I S--H-b-H--S + R'2P-NR22 $ R12 P-NR22 I Jr (49) 0 H--S s It + I products + R12P-NR22 Scheme 10 is considered to account for the observed results with the rate increase attributed to the increased concentration of the reactive intermediate (49); in addition desolvation of the ground state at higher concentrations of water may also contribute to the increase in the rate.This result is possibly relevant to enzymic catalysis where media with low aqueous content might lead to catalytic effects; it is proposed that any acidic functional group on the enzyme could therefore have stronger acidity and that desolvation of the substrate could render it more basic. 39 S. Thea G. Guanti G. Petrillo A. Hopkins and A. Williams J. Chem. SOC.,Chem. Commun. 1982 577. 40 J. M. Bonicamp and P. Haake Tetrahedron Lett. 1982 23 3127. D. G.Morris 5 Carbonyl Compounds The zero-order component in -OH which was present in the rate equation for the chlorination of ketones by hypochlorous acid and which probably represents the reaction of enolate with hypochlorous acid has provided a method for determination of pKa values of ketones in aqueous media.41 For acetone a value of ca 19 was determined.In the case of isobutyraldehyde Kresge's group4* has found a pK of 15.53 in aqueous solution; the derived enol of this aldehyde had pKa 11.63.The formation of the carbonyl compound from this enol was subject to general acid catalysis with kH+/kD+ = 2.83. Perrin and Arrheniu~~~ showed that the hemiorthoamide (51)that is formed during the hydrolysis of (50)gave only the amino-amide (52),with no (53) although this was formed subsequently under thermodynamic control. This is claimed to be the first definitive support for Deslongchamps' proposal that preferential cleavage of a tetrahedral intermediate occurs when two lone pairs are anti-periplanar to the leaving group;43a however it is pointed that the original work featured lactones which are less stable than esters and whose absence from the product(s) lessens the conviction of any mechanistic argument.(50) (51) (52) (53) The original data of De~longcharnps~~" have been revised; thus hydrolysis of 2,2-diethoxytetrahydropyrangave 2040% of 6-valerolactone shown to be a primary product and 60-80% of ethyl S-hydr~xyvalerate.~~ Conformational inver- sion of (54) is sufficiently rapid that reaction via another conformation must be allowed for. (54) Hydrolysis of the bicyclic ketal (55) has been attempted but this compound is inert in 50% aqueous dioxan at 390C.45The reason for this behaviour lies in the fact that the leaving group is fixed in an equatorial configuration by the geometry of the ring system; accordingly the lone pairs of the ring oxygen are syn-clinal to the C-OAr bond thereby minimizing n + u*overlap.The model tetrahydropyran ketal (56) is too reactive and decomposes with an estimated rate constant of 600 s-'; under the same conditions (55) is inert thereby making (56)lo'* times more reactive than (55). J. P. Guthrie J. Cossar and A. Klym J. Am. Chem. Soc. 1982 104,895. 42 Y. Chiang A. J. Kresge and P. A. Walsh J. Am. Chem. Soc. 1982,104 6122. 43 C. L. Perrin and G. M. L. Arrhenius J. Am. Chem. Soc. 1982 104,2839. P.Deslongchamps Tetrahedron 1975 31 2463. '' B. Capon and D. McL. A. Grieve Tetrahedron Lett. 1982,23,4823. 45 C. M. Evans R. Glean and A. J. Kirby J. Am. Chem. SOC.,1982,104,4706.Reaction Mechanisms -Part (ii) Polar Reactions cQo OAr OAr (55) (56) Ar = 2,4-dinitrophenyl 6 MiceUar Reactions A number of interesting papers concerned with micelles have recently appeared; and these are conveniently collected here rather than under reaction type. Nucleophilic aromatic substitution of (57) by azide ion has been found to be much faster in the micellar pseudophase than in water and is the only known reaction to behave The cationic micelles are considered to be affecting the free energy of the transition state only; in the absence of micelles the azide ion is very unreactive in this reaction. Hydrolyses of benzyl halides in particular are fas-x in sodium lauryl sulphate micelles than in their cationic counterparts where Coulombic repulsions between the micelle and the incipient carbo-cation centre are rate-retarding.47 Surfactants are known to aggregate in apolar aprotic solvents; the aggregates reversed or inverted micelles are stabilized by dipole-dipole and ion-pair interac- tions and can solubilize considerable quantities of water within their hydrophilic cavity.@ These water pools constitute a unique environment for substrates.In cyclohexane (58) exists with an aggregation number of ca 16 over a wide concentration range. Solutions of (58) and picric acid separately in chloroform or cyclohexane are colourless; however a yellow colour indicative of dissociation of the picric acid was construed as ion-pair formation and was found to occur even at very low concentrations of s~rfactant.~~ In the presence of anilino surfactants e.g.(59) the dediazoniation of simple aromatic diazonium ions proceeds via rate-determining formation of AT+ even in the positively charged Stern layer of a cationic micelle in the presence of bromide 46 C. A. Bunton J. R. Moffatt and E. Radenas J. Am. Chem. SOC.,1982,104,2653. 47 H. Al-Lohedan C. A. Bunton andM. M. Mhala J. Am. Chem. SOC.,1982,104,6654. 48 N. W. Fadnavis and J. B. F.N. Engberts J. Org. Chem.. 1982,47,2923. D. G.Morris ions.49 The product from (59),however consisted of >95% of the aromatic bromide with very little phenol; these values are typically inverted for (60). The selectivity enhancement of >380 that is experienced by (59) in favour of the formation of bromide by (59) arises since the micellar aryl cation selectively reacts with the bromide ions that are concentrated in the micellar Stern layer.A much greater rate of consumption (ca 1 x 10’) of (61) was observed during hydroxymercuration in sodium lauryl sulphate (SLS) solution as compared with aqueous tetrahydrofuran.” Moreover the ratio of rate constants k,/kb was 1.5 in aqueous tetrahydrofuran and 2.5 X 10’ in SLS [k,and k refer to the rate constants for the reaction of (61) and the monofunctionalized substrate i.e. the mono-011. a. This micelle-ind,uced chemoselectivity is considered to arise from anisotropic solubilization of the monofunctionalized substrate in the micellar site with varying degrees of penetration by water and/or the water-soluble reagent.This potentially very useful selectivity is achieved without any intrinsic difference in reactivity of the two sites. Aromatic molecules are solubilized in a relatively more polar micellar region than are simple hydrocarbons. Thus oxymercuration of p -diallylbenzene with one equivalent of mercuric acetate in the presence of SLS was essentially non-selecti~e.~’ Catalyses by reversed micelles are relevant to enzymic processes since active sites of proteolytic and lipolytic enzymes contain regions in which the polarity resembles that of micellar pools of water. Substrates usually concentrate in micellar cones of hydrophilic groups where enhanced reactivities for proton transfer and favourable entropies of activation contribute to ~atalysis.~~ With dodecylammonium propionate (62) aminolysis by these reversed micelles indicated a charge-relay mechanism similar to that for enzymic catalysis (Scheme 11).G 0-Me -C -0Ar I L .-Me-C-OAr + EtC0,H R-N-AP0,CEt I H RNH (62) J MeCONHR +OAr Scheme 11 Lower diastereoselectivities were observed when functional vesicular systems exemplified by (n-C16H33)2N+(Me)CH2CH2SH C1- were employed in the cleavage of dipeptide and tripeptide p -nitrophenyl esters such as N-carbobenzyloxy-(D or O9 R. A. Moss F. M.Dix and L. Rornsted J. Am. Chem. SOC.,1982 104 5048. J. K. Sutter and C. N. Sukenik J. Org. Chem. 1982,47,4175. ’* M.I. El Seoud R. C. Vieira and 0.A. El Seoud J. Org. Chem. 1982,47,5137. Reaction Mechanisms -Part (ii) Polar Reactions L)-Trp-(L)-Pro-PNP than when comparable micelles were used.52 The enhanced molecular restriction that is obtainable in vesicular systems does not necessarily induce greater stereoselectivity which is a function of the particular reaction mechanism.7 Miscellaneous By the use of zinc tosylate diethyl azodicarboxylate and triphenylphosphine in tetrahydrofuran alcohols are each converted into the corresponding tosylate with inversion of c~nfiguration.~~ This is exemplified by the formation of (64)from (63); one exception is however reported. The dilatometric method of determining the rate constant of hydrolysis of methylal H,C(OMe), was attended by serious kinetic complications when the initial concentration of substrate was 0.2 mol dm-3.54 Significant changes were noted in both the product composition and the acidity of the medium during a kinetic run.Reversible formation of an oxocarbo-cation was also noted from exchange experiments between H,C(OMe)2 and CD30H during hydrolysis. Proton transfers between acidic and basic centres are generally diffusion- controlled although they can be rate-determining when ApK = 0. In an investiga- tion of proton transfer between p-nitrophenol (pK is 7.16) and imidazole (pK of the conjugate acid is 6.99) it is possible to work at pH = 7 where contributions to relaxation times 7 from proton transfer uia protolysis or hydrolysis reactions are at a minimum.5s In aqueous solution at 25"C the kinetic isotope effect is kH/kD= 2.8 in accord with the maximum values previously measured between normal acid-base centres in complex systems.Phenolate oxygen adds to a neighbouring mono-alkylalkene when the two groups are juxtaposed in a system exhibiting high effective molarity. Thus at pH = 10 t1I2 for (65) is 82 s at 39 0C.56 Proton transfer is thought to be only weakly coupled with the formation of C-0 bonds and substantial carbanion character is indicated in the transition state of the reaction indicated in Scheme 12. Electrophilic aromatic bromination of activated compounds has been carried out with a new reagent hexabromocyclopentadiene in e.g. acetonitrile in the presence of Et,N (1 1).The reagent is considered to be a source of Br+ although in its 52 R. A. Moss T. Taguchi and G.0.Bizzigotti Tetrahedron Lett. 1982 23 1985. 53 I. Galynker and W. C. Still Tetrahedron Lett. 1982 23 4461. '' W. M. Schubert and D. W. Brownawell I. Am. Chem. SOC.,1982,104,3487. 55 Y. Chiang A. J. Kresge and J. F. Holzwarth,J. Chem. Soc.. Chem. Commun. SOC.,1982 1203. 5b C. M. Evans and A. J. Kirby J. Am. Chem. SOC., 1982,104,4705. D. G.Morris (65) Scheme 12 reaction with NN-dimethylaniline to give the p -bromoderivative an intense blue- green colour is attributed to a complex (66)between the amine and the undissociated hexabromo-compound.57 -BrSBr Br Br Acid-catalysed proton exchange in N-methylated amides may occur via proton-ation on oxygen (Scheme 13) which is the more basic site. A plot of the rate constants for exchange kH+,for ZCHzCONHMe versus the pK values for the corresponding carboxylic acids gives a slope of 0.43 for electron-withdrawing substituents rising to +1.84 when Z is less electron-~ithdrawing;’~ this latter value RCONHMe f H+ $ RC(OH)=hHMe + RC(OH)=NMe + H+ Scheme 13 signifies an N-protonation mechanism.In the case of N-acetylglycine methylamide which most closely resembles peptides and proteins the N-protonation exchange route is followed only to the extent of 6%; accordingly these classes of compound undergo proton exchange predominantly via the imidic acid mechanism. The diastereoisomeric complex (67)that is formed by the reaction of the ketone (68) with the chiral compound lithium (S,S)-a,a’-dimethylbenzylamide leads to (67) (68) ’’ B.Fuchs Y. Belsky E. Tartakovsky J. Zizuashvili and S. Weinman J. Chem. Soc. Chem. Commun. 1982,778. C. L. Perrin and G. M. L. Arrhenius J. Am. Chem. Soc. 1982,104,6693. Reaction Mechanisms -Part (ii)Polar Reactions the regeneration of optically active ketone (68) with an enantiomeric excess of 48% after reaction with water.59 Potassium in liquid ammonia (inter alia ) reduces racemic camphor to isoborneol (69) and borneol (70) in a ratio of 18:82 whereas when enantiomerically pure camphor is used the corresponding ratio is 62 38. The solution to this tailor-made seminar problem is given in reference 60. ’’ H. Hogeveen and L. Zwart Tetrahedron Lett. 1982 23 105. 6o V. Rautenstrauch Helv. Chim. Acta 1982,65,403.