Hydrolysis of aromatic ester

Reaction centre not conjugated with Ar group transition state has less demand for electrons than reactant. Example hydrolysis of aromatic esters by bases... 

Table 1. Spontaneous and catalysed hydrolysis of aromatic esters in water 20.2 C.pH 8.10 1/15 M phosphate buffer selected illustrative examples from...

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. 

Vera, S., Rodenas, E. Inhibiting effect of cationic micelles on the basic hydrolysis of aromatic esters. Tetrahedron 1986, 42(1), 143-149. 

Under basic conditions, the o-nitrotoluene (5) undergoes condensation with ethyl oxalate (2) to provide the a-ketoester 6. After hydrolysis of the ester functional group, the nitro moiety in 7 is then reduced to an amino function, which reacts with the carbonyl group to provide the cyclized intermediate 13. Aromatization of 13 by loss of water gives the indole-2-carboxylic acid (9). 

The typical metabolic reactions of pyrethroids are hydrolysis of an ester linkage and oxidation of an alkyl group or an aromatic ring in either acid or alcohol moiety, as shown in Fig. 6. The oxidative cleavage of the C=C bond of the prop-l-enyl... 

Mammalian esterases have been classified into three groups according to specificity for substates and inhibitors (110). In terms of overall hydrolytic activity in mammals, the most important class of esterases is that of the B-esterases, which are principally active with aliphatic esters and amides. A-Esterases are important for aromatic esters and organophosphorus esters, and C-esterases are active with acetyl esters. In general, the specificity of mammalian esterases is determined by the nature of substituent groups (acetyl, alkyl, or aryl) rather than the heteroatom (O, N, or S) that is adjacent to the carboxy group. That is, the same esterase would likely catalyze hydrolysis of an ester, amide, or thioester as long as the substituents were identical except for the heteroatom (110). 

FIGURE 6.2 Examples of the relative rates of hydrolysis of an ester, the amide of an aromatic amine, and the amide of an aliphatic amine. 

Fig. 11.9. Mechanisms and products of hydrolysis of aromatic N-sulfonyl imidates (11.66) as potential prodrugs of drugs containing sulfonamide or ester moieties [101] [102]...

Twenty-five acidic pesticides, most of which resulted from the rapid hydrolysis of the ester formulations, were isolated from the two pits. Thirty-nine substituted aromatic acids and phenols were also isolated from the pits. The source of these components was most likely the degradation of aromatic pesticides and the... 

The hydrolysis of such esters is not always possible, especially if they are sterically hindered, or if the carboxylic acid involved is aromatic, and the carbonyl group conjugated, Esters of benzoic acid, for example are very difficult to hydrolyse. 

A crude mixture of enzymes isolated from Rhodococcus sp. is used for selective hydrolysis of aromatic and aliphatic nitriles and dinitriles (117). Nitrilase accepts a wide range of substrates (Table 8). Even though many of them have low solubility in water, such as (88), the yields are in the range of 90%. Carboxylic esters are not susceptible to the hydrolysis by the enzyme so that only the cyano group of (89) is hydrolyzed. This mode of selectivity is opposite to that observed upon the chemical hydrolysis at alkaline pH, esters are more labile than nitriles. Dinitriles (90,91) can be hydrolyzed regioselectively resulting in cyanoacids in 71—91% yield. Hydrolysis of (92) proceeds via the formation of racemic amide which is then hydrolyzed to the acid in 95% ee (118). Prochiral 3-substituted glutaronitriles (93) are hydrolyzed by Phodococcus butanica in up to 71% yield with excellent selectivity (119). 

MeO-PEG-modified DPP and PYR ligands 23 and 24 were introduced by Bolm [68]. Whereas 23 showed the expected excellent enantioselectivities in the oxidation of various aromatic olefins (eemax = 99%), the catalysis of 24 gave an efficient conversion of terminal aliphatic olefins into their respective diols (eemax = 90% for 3,3-dimethyl-1-butene). As with the corresponding silica gel-bound ligand 21, sequential use of 23a led to a slight decrease in enantioselectivity in consecutive runs. This result was again attributed to partial hydrolysis of the ester moiety. After replacement of the ester by an ether function, the enantiomeric excess of the product remained constant over a period of several runs [69]. 

A quantitative assessment of the effects of head group bulk on, S k2 and E2 reactions in cationic micelles has been made.148 The kinetics of the acid-catalysed hydrolysis of methyl acetate in the presence of cationic, anionic, and non-ionic surfactants has been reported on.149 The alkaline hydrolysis of -butyl acetate with cetyltrimethylammonium bromide has also been investigated.150 The alkaline hydrolysis of aromatic and aliphatic ethyl esters in anionic and non-ionic surfactants has been studied.151 Specific salting-in effects that lead to striking substrate selectivity were observed for the hydrolysis of /j-nitrophenyl alkanoates (185 n = 2-16) catalysed by the 4-(dialkylamino)pyridine-fimctionalized polymer (186) in aqueous Tris buffer solution at pH 8 and 30 °C. The formation of a reactive catalyst-substrate complex, (185)-(186), seems to be promoted by the presence of tris(hydroxymethyl)methylammonium ion.152... 

The following are examples of other generation methods of the same kind of reactive sp2 carbon-centered radicals. Treatment of aromatic diazocarboxylate ester (11) at pH 7.2 forms the phenyl radical, through hydrolysis of the ester, decarboxylation to the phenyldiimide, and finally, reaction with molecular oxygen (eq. 11.9a). Electron transfer reduction of 1,4-diazonium (12) with Cu+ generates the corresponding /7-phenylene biradical (probably step-by-step formation) (eq. 11.9b). These simple sp2 carbon-centered radicals also destroy DNA plasmid at pH 7.6, under living-body conditions, like esperamicin [37-39]. 

The third case is in many ways the most interesting. We have seen that the alkaline hydrolysis of ethyl esters of benzoic acids (ArCC Et) has a p value of +2.6 and that this is a reasonable value for a reaction involving nucleophilic attack on a carbonyl group conjugated with the aromatic ring. The hydrolysis of the same esters in acid solution, which also involves nucleophilic attack on the same carbonyl group, has a p value of+0.1. In other words, all these esters hydrolyse at the same rate in acid solution. Neither of the previous explanations will do. We need to see the full mechanism to explain this remarkable result. 

Alkylation of potassium enolates is not always fruitful, and so counterion exchange with lithium bromide prior to addition of the electrophile has been recommended. Reduction of aromatic esters instead of acids provides a number of potential advantages. The esters tend to be more soluble than carboxylate salts, hydrogenolysis of 2-alkoxy substituents does not appear to present the s me problem, and the products are more stable. This can be important when enol ether functions are generated, allowing the necessarily acidic work-up procedures for carboxylic acids to be avoided. Indeed, the hydrolysis of enol ether functions may be very slow in aqueous acid and is best achieved through catalysis by mercury(II) nitrate. ... 

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