Hydrolysis ortho substituent effect

In Eq. 14, the reference of is shifted to that of H. The proximity effects of ortho substituents are well separated by Es and F terms according to Eq. 5. The coefficient values of Es and F terms, 0.17 and 0.77, are close enough to those for the alkaline hydrolysis of -substituted phenyl acetates 15). Thus, in support of the above discussion, the proximity effects of o-substituents are considered to be those on formation of the tetrahedral intermediate. 

Substituent effects on the A,u I reaction have been studied by Bender and Chen55. These authors measured the rates of hydrolysis of a series of 4-substituted 2,6-dimethylbenzoates in 9.70 M sulphuric acid at 25°C, and found that the values for the first-order coefficients with 4-methoxy, 4-methyl, 4-unsubstituted and 4-bromo-compounds (5.0, 0.37, 0.033 and 0.01 x I0 4 sec-1, respectively) are satisfactorily correlated by the Hammett equation, following cr+ with a slope p = —3.22. Since the esters are not fully protonated in 9.70 M H2SOj, part of this factor is due to the effects of the 4-substituent on the protonation equilibrium, p for the protonation of substituted benzoic acids is about — l35, but is likely to be considerably smaller for di-ortho-substituted compounds, since the conjugative interaction of the p-substituents with the protonated carboxyl group requires coplanarity with the ring. 

Orf/io-substituents in general reduce the rates of acid-catalyzed ester formation and hydrolysis. Some typical data are collected in Table 20. In each series the rate coefficient decreases as the size of the ortho substituent increases. Only the smallest substituent of all, the fluorine atom, does not have a marked effect. 

The ortho substituent constants, s°, on the other hand, gave no significant correlation with van der Waal s radii. The effects of groups in the ortho position are fully accounted for in terms of o-, and steric effects of groups in the ortho position are constant, negligible, or non-existent251. This result was confirmed by an analysis of the data for acid-catalyzed ester hydrolysis and formation, including those of Tables 20 and 22. 

Generally, the rate of alkaline hydrolysis of a series of substituted phenyl benzoates was decreased in the presence of 0.5 m BiuNBr, the retardation being larger for esters with electron-donating substituents. The data from 22 esters were fitted to a multiparameter equation, the results showing that solvent electrophilicity was the main factor responsible for changes in the ortho, para and meta polar substituent effects with medium.15... 

Rates of the alkaline hydrolysis of 12 ortho-, meta- and ) ara-X-substituted phenyl tosylates, 4-MeC6H4S02C6H4X, in aqueous 0.5 m Bu4NBr over a wide temperature range have been analysed using the modified Fujita-Nishioka multi-parameter equation. It was concluded from both these and previously reported data by the same group that solvent electrophilicity was the main factor responsible for changes in the ortho, meta and para polar substituent effects with medium.60... 

Sotomatsu, T. and Fujita, T. (1989). The Steric Effect of Ortho Substituents on the Acidic Hydrolysis of Benzamides. J. Org. Chem., 54,4443-4448. 

The rate determining step is the formation of a carbonium ion and as expected, substituents that are able to stabilize the carbonium ion will strongly accelerate the hydrolysis reaction. This effect is shown in Table 1. However, as also shown in Table 1, this is not true for ortho esters where substituent effects are much smaller than would be predicted by analogy with acetal or ketal hydrolysis, and in some cases are in the opposite direction. These data are consistent with the hypothesis that in ortho ester hydrolysis, there is very little carbonium ion character in the transition state and that in the hydrolysis of ortho esters, addition of a proton is concerted with the breaking of a C-O bond. 

The polar effects of most m(a and para substituents on the second-order rates of hydrolysis of aromatic esters have demonstrated the marked influence on the energy of activation with little affect to the entropy term. In contrast, ortho substituents alter both the activation energy and the entropy factor. As a general rule, the alkaline hydrolysis of aromatic carboxylic esters is accelerated by substituents with —I, —R effects and is retarded by substituents with +/, +R effects. 

The effect of a substituent may be substantially modified by fast, concurrent, reversible addition of the nucleophile to an electrophilic center in the substituent. Ortho- and para-CS.0 and pam-CN groups have been found by Miller and co-workers to have a much reduced activating effect on the displacement of halogen in 2-nitrohaloben-zenes with methoxide ion [reversible formation of hemiacetal (143) and imido ester anions (144)] than with azide ion (less interaction) or thiocyanate (little, if any, interaction). Formation of 0-acyl derivatives of 0x0 derivatives or of A-oxides, hydrogen bonding to these moieties, and ionization of substituents are other examples of reversible and often relatively complete modifications under reaction conditions. If the interaction is irreversible, such as hydrolysis of a... 

If we compare the acid strengths Ka) of a series of substituted benzoic acids with the strength of benzoic acid itself (Table 26-4), we see that there are considerable variations with the nature of the substituent and its ring position, ortho, meta, or para. Thus all three nitrobenzoic acids are appreciably stronger than benzoic acid in the order ortho para > meta. A methoxy substituent in the ortho or meta position has a smaller acid-strengthening effect, and in the para position decreases the acid strength relative to benzoic acid. Rate effects also are produced by different substituents, as is evident from the data in Table 26-5 for basic hydrolysis of some substituted ethyl benzoates. A nitro substituent increases the rate, whereas methyl and methoxy substituents decrease the rate relative to that of the unsubstituted ester. 

In the hydrolysis of diethylphenyl orthoformate no general base catalysis is observed. The steric effects of substituents on the imidazole catalyst are very small, and the activation parameters have been shown to have large negative entropies. These observations, in conjunction with a solvent isotope effect, point to participation of water molecules in the transition state, i.e., at least one water molecule intervenes between imidazolium ion and the ortho ester (see (66)). General acid catalysis is assumed <87JCS(P2)669>. 

It is difficult to replace aromatically bound halogen by a hydroxyl group. Hydrolysis of halobenzenes has been effected under pressure in the presence of alkali or after addition of catalytically active substances.526 There are numerous patents describing, e.g., the conversion of chlorobenzene into phenol 527 and phenols have been obtained from bromobenzene derivatives in an autoclave in the presence of copper catalysts.528 Hydrolysis of halo-benzene derivatives is easier if they contain electron-attracting substituents in the ortho- or /wra-position to the halogen. 

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