Solvolysis internal return

We have previously discussed the possibilities of racemization or inversion of the product RS of a solvolysis reaction. However, the formation of an ion pair followed by internal return can also affect the stereochemistry of the substrate molecule RX. Cases have been found where internal return racemizes an original optically active RX, an example being solvolysis in aqueous acetone of a-p-anisylethyl p-nitrobenzoate, while in other cases partial or complete retention is found, for example, solvolysis in aqueous acetone of p-chloro benzhydryl p-nitrobenzoate. the pathway RX R+X some cases where internal return involves racemization, it has been shown that such racemization is faster than solvolysis. For example, optically active p-chlorobenzhydryl chloride racemizes 30 times faster than it solvolyzes in acetic acid. ... 

Another detectable example of internal return is afforded by the solvolysis of xo-norborriylbromobenzenesulfonate (XL) it racemizes from 40 to 240% faster than it produces bromobenzenesulfonic acid, yet both reactions are strictly first order. The racemization reaction is kinetically independent of bulk bromobenzenesulfonate concentration but its rate is dependent on the nature of the solvent, pyridine being less effective than alcohol, acetic acid, or aqueous acetone.238 The behavior of 3-phenyl-2-butyl- -toluenesulfonate is similar.250... 

A Global scheme for solvolysis 2 Clocks for reactions of ion pairs 3 Addition of solvent to carbocation-anion pairs i Protonation of a carbocation-anion pair 11 Isomerization of ion pair reaction intermediates Reorganization of ion pairs in water 13 Internal return of isotopically labeled ion pairs Racemization of ion pairs 22 Concluding remarks 24 Acknowledgements 24 References 24... 

We have examined the competing isomerization and solvolysis reactions of 1-4-(methylphenyl)ethyl pentafluorobenzoate with two goals in mind (1) We wanted to use the increased sensitivity of modern analytical methods to extend oxygen-18 scrambling studies to mostly aqueous solutions, where we have obtained extensive data for nucleophilic substitution reactions of 1-phenylethyl derivatives. (2) We were interested in comparing the first-order rate constant for internal return of a carbocation-carboxylate anion pair with the corresponding second-order rate constant for the bimolecular combination of the same carbocation with a carboxylate anion, in order to examine the effect of aqueous solvation of free carboxylate anions on their reactivity toward addition to carbocations. 

Scheme 5 depicts Winstein s complete solvolysis mechanism.29 Ion-pair return can be from the intimate ion pair (ion-pair return or internal return), from the external ion pair (external ion-pair return), or from the free ions (external ion return). The term external return refers to the sum of external ion-pair return and external ion return. The special salt effect operates by diversion of the external.ion pair, probably through the mechanism shown in Equation 519, so that it can no longer... 

Solvolysis of (44) gives the doubly destabilized cation (45), which shows a preference for internal return.89 Compound (44) is 109 times less reactive than is (46), of which 106 is attributed to the antiaromaticity of (45) and 103 to the presence of the electron-withdrawing CF3.89 The similarity of the destabilized cation (47) and the doubly protonated species (48) is demonstrated by the similar electrophilic cyclizations that these species undergo.90 Double-bond protonation was not observed.90 Compound (49) undergoes aniline-catalysed ring closure as shown to give (50), rather than the expected isomer (51).91... 

Many alkyl halides and arenesulfonates (R—X) undergo first-order solvolysis in ionising solvents (SOH) and the essential experimental features maybe accommodated by the generic mechanism shown in Scheme 4.4. The mechanism includes reversible ionisation of the covalent substrate to give a contact (intimate) ion pair, R+ X-, which undergoes internal return or nucleophilic capture by the solvent (in some cases, there is evidence for the intervention of solvent-separated ion pairs, and even fully dissociated ion pairs, but the minimalist mechanism of Scheme 4.4 serves our present purpose adequately) [13]. 

When R—X is enantiomerically enriched exo-2-norbornyl 4-bromobenzenesulfonate (brosylate), 1 in Fig. 4.5, and SOH is aqueous ethanol, for example, solvolysis is accompanied by racemisation. However, the rate of racemisation is faster than the rate of product formation, and starting material isolated before completion of the solvolysis is partially racemised [14]. The most economical interpretation of these results (and much other evidence, see Chapter 7) is that R+ X- includes the achiral nonclassical carbenium ion (3 in Fig. 4.5), and the ion pair undergoes internal return faster than nucleophilic capture. In other words, k- > k2 in Scheme 4.4, the precise value of the ratio k- lk2 depending upon the particular solvent, and the greater this ratio, the closer the initial reversible process approaches a pre-equilibrium. 

In contrast, when R—X in Scheme 4.4 is enantiomerically enriched endo-2-norbornyl brosylate (2 in Fig. 4.5) under the same reaction conditions, solvolysis is still accompanied by racemisation, but the rate of racemisation is identical with that of product formation [14]. The achiral carbocation in this reaction, therefore, is captured by solvent much faster than it can undergo internal return, i.e. k2 i in Scheme 4.4. In this case, therefore, the initial ionisation is the rate-determining step. 

A detailed and elegant study of the SnI solvolysis reactions of several substituted 1-phenylethyl tosylates in 50% aqueous TEE has enabled the rates of (1) separation of the carbocation-ion pair to the free carbocation, (2) internal return with the scrambling of oxygen isotopes in the leaving group, (3) racemization of the chiral substrate that formed the carbocation-ion pair, and (4) attack by solvent to be determined.122... 

It may be argued that the evidence for ion pair intermediates is too indirect, since it has not been established that the ion pairs undergoing 18 O-scrambling or interned return are the same as those undergoing solvolysis. Evidence for ion pairs would then be explained by side-reactions and the solvolytic reactions for which nucleophilic solvent assistance is greater... 

Winstein (1957c). They argued that during solvolysis of neophyl substrates [46, X = Cl, Br] internal return from the proposed phenonium ion-pair intermediate [47] would yield the tertiary derivative [48] (Fig. 13) and this would solvolyse rapidly. Thus, the titrimetric rate constants should correspond to the ionization rate constant k j (Fig. 2). Later neophyl tosylate [46, X = OTs] and its p-methoxy derivative were used (Smith et al., 1961 Diaz et al., 1968b Yamataka et al., 1973), and recently Schadt et al. (1976) defined as a scale of solvent ionizing power for tosylates, designated F2-AdOTs or Yqt, using eqn (5) but based on 2-adamantyl tosylate [6] instead of t-butyl chloride. A correlation of the rates of solvolysis of neophyl tosylate with F0 Xs (Fig. 14) is satisfactory (correlation coefficient... 

The large amounts of five- and six-membered cyclic tosylates, products of internal return (49% yield in one case 12a of Table 3) points also to a highly selective intermediate, although the reason for such a remarkable selectivity towards external nucleophiles is not clear. On the other hand, acetolysis of 6-phenyl-5-hexynyl brosylate, which is apparently anchimerically assisted by the triple bond (4>bs./ caic. = 1 6) yields only the five-membered ring product in addition to open-chain solvolysis products (13 of Table 3). The effect of the phenyl group in orienting the oyclization reaction would indicate that intermediate species like 43 may become important when R =Ph. 

The overall consumption rate of the covalent precursor (ks) is determined by HPLC and/or titration measurements this correlates with monomer consumption in propagation. The rate of racemization of optically active 1-phenylethyl chloride (ka) is determined by polarimetric measurements, Racemization is usually faster than solvolysis, confirming that activation is reversible and that internal return may occur before the carbenium ion reacts with an external nucleophile, Racemization requires not only that the C—Cl bond of the covalent precursor is broken, but that the lifetime of the ion pair is long enough for the flat carbenium ion to rotate, such that both sides of the carbenium ion are completely equivalent as shown in Eq. 18. 

The recovered tosylates on the other hand contained more D at C(9) than the isolated acetates (approximately twice as much in the recovered tosylate from the solvolysis of [395] compared with that recovered from the solvolysis of the mixture). These results indicated stereospecific rearrangement via internal return of the tosylate ion pair. 

For (58) and (60) keq was found to equal krac80,82. Thus it appears that internal return in allylic systems results in racemization and complete oxygen equilibration. However, this result is also consistent with an ion pair (63) which retains coordination of the ether oxygen to the carbon atom from which it departed. (63) would produce an equimolar mixture of (62a) and (62b). Determination of the 180 distributions of both recovered enantiomers from the solvolysis of (60) revealed identical scrambling, i.e. rapid interconversion of ion pairs (63) and (64)S2 With (55), however, predominant product formation from (63) was indicated by excess carbonyl-180 in the inverted ester and excess ether-180 in the ester of retained configuration80. ... 

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