Methyl benzoates, alkaline hydrolysis

Example 4.3. The p value for alkaline saponification of methyl esters of substituted benzoic acids is 2.38, and the rate constant for saponification of methyl benzoate under the conditions of interest is 2 x 10 s . Calculate the rate constant for the hydrolysis... 

The intermediates 74 and 76 can now lose OR to give the acid (not shown in the equations given), or they can lose OH to regenerate the carboxylic ester. If 74 goes back to ester, the ester will still be labeled, but if 76 reverts to ester, the 0 will be lost. A test of the two possible mechanisms is to stop the reaction before completion and to analyze the recovered ester for 0. This is just what was done by Bender, who found that in alkaline hydrolysis of methyl, ethyl, and isopropyl benzoates, the esters had lost 0. A similar experiment carried out for acid-Catalyzed hydrolysis of ethyl benzoate showed that here too the ester lost However, alkaline hydrolysis of substimted benzyl benzoates showed no loss. This result does not necessarily mean that no tetrahedral intermediate is involved in this case. If 74 and 76 do not revert to ester, but go entirely to acid, no loss will be found even with a tetrahedral intermediate. In the case of benzyl benzoates this may very well be happening, because formation of the acid relieves steric strain. Another possibility is that 74 loses OR before it can become protonated to 75. Even the experiments that do show loss do not prove the existence of the tetrahedral intermediate, since it is possible that is lost by some independent process not leading to ester hydrolysis. To deal with this possibility. Bender and Heck measured the rate of loss in the hydrolysis of ethyl trifluorothioloacetate- 0 ... 

Figure 20. Relations between AG and between E values for two related reactions alkaline hydrolysis of substituted methyl and ethyl benzoates (188, 228).

Flutolanil and its metabolites containing the 2-(trifluoromethyl)benzanilide moiety are converted to methyl 2-(trifluoromethyl)benzoate (2-TFBA Me-ester) by alkaline hydrolysis and methylation for GC/MS analyses. 

The observation of lsO-exchange between the carbonyl oxygen atom of an ester and solvent is evidence for the formation of a tetrahedral addition compound, but not proof that this actually lies on the reaction pathway. But the behaviour of the exchange and hydrolysis reactions is so similar that there can be little doubt that this is, in fact, the case. The evidence is most complete for alkaline hydrolysis (see p. 163). One further piece of evidence obtained under acidic conditions is the observation47 that there is no exchange between the solvent and the carbonyl-lsO-labelled ester when methyl 2,4,6-trimethyl-benzoate is hydrolyzed in 3.09,5.78 and 11.5 M sulphuric acid. Other evidence makes it clear that this ester is hydrolyzed by the Aac1 mechanism, and that no reversible addition of water is expected. 

The effects of polar substituents on the alkaline hydrolysis of esters are well-established. Since the rate of the reaction is determined largely by the rate of addition of hydroxide ion to the carbonyl group of the ester, any substituent which withdraws electrons from the carbonyl group will increase the reactivity of the ester. The most accessible quantitative measure of the effect is the Hammett or Taft reaction constant, and a large number of measurements are available. Taft et al.2i0 found p = 2.53 for the base-catalyzed methanolysis of meta- and para-substituted (/)-menthyl benzoates, closely similar to the known value of p = 2.37 for the alkaline hydrolysis of substituted ethyl benzoates. Jones and Sloane s value239, obtained with five esters, of p = 2.41 for the methoxyl exchange reaction of substituted methyl benzoates in methanol, is almost identical. 

For more remote substitution p is expected to be smaller. Thus Hay and Porter-28 found p = 0.6 for the alkaline hydrolysis of the methyl esters of a-amino acids, RCH(NH2)COOCH.3 in water at 25°C. However, higher sensitivities are possible if the geometry of the system is such that the direct transmission of polar effects becomes more important. For example, Roberts and Moreland245 found that the effects of substituents in the 4 position of ethyl bicyclo-[2.2.2]octane-l-carboxylates (28) on the hydrolysis in 88% ethanol at 30°C are comparable to those observed for meta- anti para-substituted benzoates (p = 2.24), and a similar, though smaller, effect, is observed for methyl rrarts-4-substituted cyclohexanecarboxylates (29). 

Dimethyl-L-arabinose (XXXIX) has been synthesized as follows.48 Methyl 3,4-isopropylidene-/3-L-arabopyranoside (XXXVII) was converted into the 2-benzoate and the isopropylidene residue eliminated from the product with methanolic hydrogen chloride to give methyl 2-benzoyl-/J-L-arabopyranoside (XXXVIII) from which on methylation, removal of the benzoyl residue by alkaline hydrolysis and of the glycosidic residue by acid hydrolysis, 3,4-dimethyl-L-arabinose was obtained. 

The lifetime of the tetrahedral intermediate formed during the alkaline hydrolysis of -substituted methyl benzoates has been shown to be very short, of the order of 10 seconds or shorter (Bender and Thomas, 1961b). The experimental evidence for this conclusion comes from measurements of the substituent effect on It would be ex-... 

The rates of alkaline hydrolysis of methyl pyridazine-3- and -4-carboxylate were correlated with those of pyridinecarboxylates and benzoates. Diethyl pyridazine-4,5-dicarboxylate (214) reacts with 1,3-diphenylguanidine in the presence of sodium hydride to give the spiro compounds 215, the structure of which was determined by X-ray analysis. Related spiro compounds were obtained from the above ester and esters of glutaric or acetonedicar-boxylic acids. 5-Aminopyridazine-4-carboxylic acid is simply synthesized from the 5-carboxamido analog by Hofmann rearrangement. ... 

The alkaline hydrolysis of methyl 2,4,6-trimethylbenzoate (33 R = R = CH3) (Bender and Dewey, 1956) and of methyl 2,4,6-triphenyl-benzoate (33 R = C6Hb R = CH3) (Bunton et al., 1955a) are both found to proceed via acyl-oxygen fission, accompanied by some oxygen exchange indicating the formation of a tetrahedral intermediate. 

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