Secondary systems, solvolysis

Use of other methods has contributed further to the emerging picture of solvolysis of most secondary systems as being solvent-assisted. For example, the solvolysis rate acceleration on substituting a-hydrogen by CH3 in 2-adamantyl bromide is 107 5, much larger than that found for other secondary—tertiary pairs such as isopropyl-/-butyl. In molecules less hindered than 2-adamantyl, the secondary substrate is accelerated by nucleophilic attack of solvent.100 Rate accelerations and product distributions found on adding azide ion to solvolysis mixtures (Problem 4) also provide confirmatory evidence for these conclu-... 

Solvent Dependence of Reactivity. Solvolysis reactions were investigated to obtain structure-reactivity relationships, but these studies were complicated by the solvent dependence of relative rates (Table I). These results show a 1010 variation in relative rates of solvolyses of methyl and 2-adamantyl tosylates (2-AdOTs) in trifluoroacetic acid (TFA) compared with those of ethanolysis. Even for two secondary systems, relative rates for 2-AdOTs-(CH3)2CHOTs vary from 36 in trifluoroacetic acid to 0.0011 in ethanol (4). Hence, separate intrinsic structural effects must be separated from solvent-induced effects. 

Table 5 shows that for tertiary systems the exo endo rate ratio predicted only with steric factors agrees with experiments in the case of secondary systems there is no such accordance. Thus the difference in activation ener for the solvolysis of secondary exo- and endo-derivatives which is due to the a-participation upon solvolysis of exo isomer coincides by chance with the difference for tertiary systems due to a steric strain decrease in the transition state for exo isomers owing to the removal of 2-endo-alkyl from 6-endo-hydrogen The relief of the steric strain in the transition state of solvolysis of 2-exo-esters makes it necessary to correct for the steric accelerating effect in tertiary systems in comparing tertiary and secondary substrates. 

To elucidate the formation of the nonclassical 2-norbornyl ion 5 in secondary systems the effect of the substituents at CS C and C on the solvolysis rate of 2-norbomyl derivatives was widely studied. Since on solvolysis of... 

In contrast to Brown s assertions and in accord with Winstein s and Trifan s assumption, the solvolysis of these secondary systems proceeds with anchimeric acceleration. This is concluded from the following facts a) the exo endo rate ratio for 2-norbomyl systems is 10 -10 as the reaction rate of the endo isomer is not anomalous (see above), hende the exo isomer reacts at an elevated rate b) the rate of solvolysis of exo isomers is 10 to 10 times as high as that calculated according to the semiempirical scheme from only steric effects c) the ratio of the reaction rate of secondary 2-exo-norbomyl systems to the solvolysis rate of secondary cyclopentyl analogues is 100 times as great as that of tert-2-exo-norbomyl derivatives and tert-cyclopentyl analogues since tert-2-norbomyl derivatives are solvolyzed without anchimeric assistance, the factor of 100 characterizes tentatively the amount of anchimeric assistance in the secondary 2-exo-norbornyl systems d) exo- and endo-6-substituents decrease the solvolysis rate of 2-exo-norbomyl tosylate this cannot be accounted for without participation of the electrons of the 1,6 bond in the transition state their participation increases the non-bonded interaction due to a decrease in the C -C distance. 

Nucleophilic substitution reactions that occur under conditions of amine deamination often differ significantly in stereochemistry, compared with that seen in halide or arenesulfonate solvolysis. The results of four key substrates are summarized in Table 5.13. It can be seen (entry 1) that displacement of nitrogen on the 1-butyldiazonium ion is much less stereospecific than the 100% inversion observed on acetolysis of the corresponding brosylate. Similarly, the secondary system (entry 2) affords 2-butyl acetate with only 28% inversion of configuration. Furthermore, a crossover to net retention of configuration is observed as the alkyl group becomes better able to stabilize a carbonium ion. The small net retention (10%) observed in deamination of 1-phenylethylamine increases to 28% retention in the tertiary benzylic system 2-phenyl-2-butylamine. 

Another method " for predicting the rates of cyclic secondary systems (17) has recently become available. The method is a refinement of the a-Me/H ratio method of estimating the magnitude of solvent and anchi-meric assistance. Since a linear or plot (Taft plot) is observed for the solvolysis of acyclic tertiary derivatives (18) in various solvents, by placing... 

An excellent review of the use of secondary a and isotope effects in the norbomyl system has recently been written by Scheppele (1972). We shall briefly summarize a few of the factors and conclusions arrived at because of their relevance to the interpretation of other solvolysis data, but the interested reader should turn to that article and the original sources quoted for a more extensive discussion. 

The behaviour of the butyl system provides important information on the nature of the intermediate formed during the rearrangement of the isobutyl to the 2-butyl cation. Thus, from the observation that isobutyl chloride yields n-butane which has exchanged one proton with the acid, while the solvolysis of 2-butyl chloride in the same acid (2% HjO), yields unexchanged n-butane one might deduce that an intermediate was formed during the former s solvolysis which exchanged one proton with the acid before it converted to a secondary butyl ion. A reasonable mechanism is shown in Scheme 1. 

In contrast to typical mono- or acyclic substrates (e. g.,isopropyl), 2-adaman-tyl derivatives are also found to be insensitive to changes in solvent nucleophilicity. A variety of criteria, summarized in Table 13, establish this point. In all cases, the behavior of 2-adamantyl tosylate is comparable to that observed for its tertiary isomer but quite unlike that observed for the isopropyl derivative. Significant nucleophilic solvent participation is indicated in the solvolysis reactions of the isopropyl system. The 2-adamantyl system, on the other hand, appears to be a unique case of limiting solvolysis in a secondary substrate 296). The 2-adamantyl/ isopropyl ratios in various solvents therefore provide a measure of the minimum rate enhancement due to nucleophilic solvent assistance in the isopropyl system 297). 

The slightly lower r value for the solvolysis of system [15] than for the a-methyl analogue [14], is presumably due to incomplete coplanarity of the aryl group with the cationic p-orbital in the transition state of [15] (Tsuji et al., 1990). In the solvolysis of 2,2-dimethylindan-l-yl chlorides (cf. Table 3), the vacant p-orbital developed at the benzylic position is in a proper stereoelectronic conformation to overlap the benzene ir-system and the r value is practically identical with that observed for the solvolysis of [14]-C1 (Fujio et al., 1992c). Consequently, the resonance demand for the SnI solvolysis of secondary a-alkylbenzyl systems must be appreciably and intrinsically higher than that for the solvolysis of tertiary a,a-dialkylbenzyl systems. 

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