Solvolysis reactions substrates

A scale for solvent ionizing power, K+, applicable in solvolysis reactions of cationic substrates, has been developed. For example,... 

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. ... 

The normal effect of NO2 on S l solvolysis of substrates such as benzhydryl chloride is to retard reaction. Thus in the ethanolysis of XQdLjCIIPhCI, logfc values (first-order rate coefficients, s 1) are as follows (50 °C) H, —3.05 m-N()2, —5.64 p-NCT. —5.99198. The p value for this reaction is about —3.7, so the logfc values for the m-NCT and p-NCT derivatives correspond fairly closely to the a values of 0.71 (or 0.73) and 0.78, respectively (Section III.B). This reaction is, of course, strongly accelerated by —R para-substituents through cross-conjugation in the carbocationic transition state (Section n.A). 

This reaction proceeds via the transition state illustrated in Fig. 10.2. An Sn2 reaction (second order nucleophilic substitution) in the rate limiting step involves the attack of the nucleophilic reagent on the rear of the (usually carbon) atom to which the leaving group is attached. The rate is thus proportional to both the concentration of nucleophile and substrate and is therefore second order. On the other hand, in an SnI reaction the rate limiting step ordinarily involves the first order formation of an active intermediate (a carbonium ion or partial carbonium ion, for example,) followed by a much more rapid conversion to product. A sampling of a and 3 2° deuterium isotope effects on some SnI and Sn2 solvolysis reactions (i.e. a reaction between the substrate and the solvent medium) is shown in Table 10.2. The... 

The addition of water to a free carbocation intermediate of solvolysis can be distinguished from addition to an ion-pair intermediate by an examination of common ion inhibition of solvolysis. Common leaving group inhibition of solvolysis is observed when the leaving group ion (X ) acts, by mass action, to convert the free carbocation (R , Scheme 5A) to substrate (R-X). This results in a decrease in the steady-state concentration of R that leads directly to a decrease in the velocity of solvolysis. Some fraction of the solvolysis reaction products form by direct addition of solvent to the carbocation-anion pair intermediate. The external... 

The situation is different for solvolysis reactions in most other solvents, where the intermolecular interactions between ions at an ion pair are stronger than the compensating interactions with solvent that develop when the ion pair separates to free ions. This favors the observation of racemization during solvolysis. There are numerous reports from studies on solvolysis in solvents with relatively low dielectric constant such as acetic acid, of polarimetric rate constants (fe , s ) for racemization of chiral substrates that greatly exceed the titrimetric rate constant (fet, s ) for formation of acid from the solvolysis reaction. ... 

There is an ongoing controversy about whether there is any stabilization of the transition state for nucleophilic substitution at tertiary aliphatic carbon from interaction with nucleophilic solvent." ° This controversy has developed with the increasing sophistication of experiments to characterize solvent effects on the rate constants for solvolysis reactions. Grunwald and Winstein determined rate constants for solvolysis of tert-butyl chloride in a wide variety of solvents and used these data to define the solvent ionizing parameter T (Eq. 3). They next found that rate constants for solvolysis of primary and secondary aliphatic carbon show a smaller sensitivity (m) to changes in Y than those for the parent solvolysis reaction of tert-butyl chloride (for which m = 1 by definition). A second term was added ( N) to account for the effect of changes in solvent nucleophilicity on obsd that result from transition state stabilization by a nucleophilic interaction between solvent and substrate. It was first assumed that there is no significant stabilization of the transition state for solvolysis of tert-butyl chloride from such a nucleophilic interaction. However, a close examination of extensive rate data revealed, in some cases, a correlation between rate constants for solvolysis of fert-butyl derivatives and solvent nucleophicity. " ... 

Stabilization conferred by aromatic hyperconjugation resolves a puzzle concerning the relative stabilities of arenonium ions. As judged by rates of solvolysis reactions, normally a phenyl group is more effective than vinyl in stabilizing a carbocation center.166 This difference is moderated for cycloalkyl substrates, so that benzoannelation has little effect, for example, on the rate of hydrolysis of 3-chlorocyclohexene (Cagney H, Kudavalli JS, More O Ferrall... 

Since the solvolysis reactions of bridgehead substrates are mechanistically uncomplicated (i.e. competing elimination is highly unlikely187 ns-H9) an(j backside solvent participation is impossible), they provide ideal models for limiting carbonium ion behavior. Adamantyl derivatives have become the substrates of choice for this purpose due to their availability and convenient reactivity. 

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). 

A final example of the utility of adamantyl substrates as model systems in mechanistic investigations is provided by 1-adamantylcarbinyl derivatives. Detailed product and rate constant determinations of 1-adamantylcarbinyl solvolyses have been interpreted relative to the mechanism of the solvolysis reactions of neopentyl systems in general. 

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... 

The stereochemical course of solvolysis of a diastereomeric /3-bromo-silane, which was found to be trans elimination, as well as the observation of 1,2-silyl group migration in a process of substitution at the 0 carbon 143) are evidence of anchimeric assistance of the silyl group in ionization of the bond to the /3 carbon. It was further noticed 144) that after quenching the solvolysis reaction of /3-bromo-/3-dideuterioethylsilane the substrate recovered is a mixture of a and /3 deuterated isomers [Eq. (33)]. These... 

The correlation of two alternative measures of selectivity has recently been proposed as a mechanistic tool in solvolysis reactions (Pross and Koren, 1975). Thus a plot of the selectivities for a series of substrates measured both by competition between azide ion and water ( N /kw ), and by ethanol and water ( E/AW ) was found to be linear and of unit slope. This result strongly reinforces the view that... 

Traditionally, relative stabilities of carbocations have been derived from the comparison of the rates of solvolysis reactions following the SN1 mechanism, for which the designation Dm + An has recently been proposed [36], The comparison of solvolytic rate constants for substrates of a large structural variety is hampered by the fact that the published solvolysis rates refer to different solvents, different temperatures, and precursors with different leaving groups. Dau-Schmidt has, therefore, converted solvolysis rates of a manifold of alkyl chlorides and bromides to standard conditions, i.e., soiv of RC1 in 100% EtOH at 25° C (Scheme 6) [37]. Although from a theoretical point of view, ethanol is not an ideal solvent for observing unassisted SN 1-type reactions (nucleophilic solvent participation), it has been selected as the reference solvent because most available experimental data have been collected in solvents of comparable nucleophilicity, a fact which made conversions to 100% ethanol relatively unproblematic [38],... 

Another interesting example is a study on rate data in solvolysis reactions.[19]. It was found that exo substituted norbomane systems were classified to belong to the same class as substrates which were known to give rise to stabilized carbocations. 

The sialic acid structure incorporates a carboxylate at the anomeric centre, which can be inductively electron donating in its deprotonated form and inductively electron withdrawing when protonated, as well as deoxygenation of the position next to the anomeric centre. These features make sialosyl cations more stable than simple aldopyranosyl cations, and hydrolysis and solvolysis reactions have been investigated using the substrates shown in Figure 3.24. 

Solvolysis reactions of vinylic substrates in binary protic solvents are numerous (69), but in the majority of cases, the distribution of the two products is not useful for evaluating the relative reactivities of the two solvents. The main reason is that the vinyl ethers formed in H20-R0H mixtures, the vinyl formates, and sometimes the vinyl acetates formed in HCOOH-AcOH or AcOH-H20 mixtures are frequently unstable under the solvolytic conditions. Their hydrolysis to the ketones will give erroneous capture ratios. In addition, in most cases the nature of the product-forming intermediate is not clear and it is frequently the ion pair. 

Other reaction substrate variations that will not be covered in this chapter include the NaBHt/TFA reductive cleavage of 1,4-epoxy-1,4-dihydronaphthalenes25 and benzylic ozonides,26 the tandem solvolysis-reduction of triarylmethyl chlorides,27 the cleavage of ferrocenyl ketone hydrazines,28 and the reduction of benzophenones to diarylmethanols ( ).29... 

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