Carboxylic acid esters alkaline hydrolysis

Carbon-11 labelled calcium channel antagonists C-nifedipine, C-nisoldipine, C-nitrendipine and C-CFj-nifedipine possessing vasodilating and hypotensive properties have been synthesized using a modified Hantzsch-type cyclocondensation proce-dure . Condensation of aldehydes 242, 243 and 244 with 3-aminocrotonic acid esters 245, 246, 247 and with acetoacetic ester 248 produced in one pot after 12 hours reflux in dry ethanol the methyl sulphonylethyl protected dihydropyridines 249-252. Deprotection of the carboxylic acids by alkaline hydrolysis followed by conversion into the dihydropyridine monocarboxylic acids 253-256 gave potassium salts in situ, and subsequent methylation with CH3I produced the corresponding labelled title compounds 257-260 (equation 102),... 

The first term, representing acid-"catalyzed" hydrolysis, is important in reactions of carboxylic acid esters but is relatively unimportant in loss of phosphate triesters and is totally absent for the halogenated alkanes and alkenes. Alkaline hydrolysis, the mechanism indicated by the third term in Equation (2), dominates degradation of pentachloroethane and 1,1,2,2-tetrachloroethane, even at pH 7. Carbon tetrachloride, TCA, 2,2-dichloropropane, and other "gem" haloalkanes hydrolyze only by the neutral mechanism (Fells and Molewyn-Hughes, 1958 Molewyn-Hughes, 1953). Monohaloalkanes show alkaline hydrolysis only in basic solutions as concentrated as 0.01-1.0 molar OH- (Mabey and Mill, 1978). In fact, the terms in Equation(2) can be even more complex both elimination and substitution pathways can operate, leading to different products, and a true unimolecular process can result from initial bond breaking in the reactant molecule. 

Nitriles undergo both acid and alkaline hydrolysis to give the corresponding amide first, and then the carboxylic acid ester and ammonia (equations (13) and (14)) ... 

Collette (1992) proposed a novel approach to developing and applying QSARs for the alkaline hydrolysis of carboxylic acid esters using infrared (IR) spectroscopic data. The concept is to extend QSARs to a larger and more diverse group of organic compounds by including the structural information encoded in IR spectra. Such data are available from spectral data bases, but even in the absence of literature data, IR frequencies are readily measurable. 

Log of the alkaline hydrolysis rate constant vs. difference in carbon-oxygen stretching frequency for 12 carboxylic acid esters. 

Butyl benzyl phthalate is a mixed carboxylic acid ester formed by the condensation of phthalic acid with two different alcohols. No literature values could be found nor any directly applicable QSARs. Based on known reactivity of carboxylic acid esters, any acid hydrolysis should be very slow. Neutral hydrolysis, while reported in the literature for certain reactive esters, is not likely for the phthalate esters. The carboxylic acid esters are most labile to alkaline hydrolysis (Mabey and Mill, 1978). 

Method E, which assumes the N(7)-C(7a) bond formation in the cyclization step, is also rarely used in the synthesis of thienopyridines. For example, the method (1997H255, 1998JMC(E)33, 1998PS21) for the preparation of 4-oxo-4,7-di-hydrothieno[2,3-Z>]pyridine-5-carboxylic acid esters 54 is based on intramolecular /V-nucleophilic substitution of (E/Z)-aminomethylene derivatives of (2,5-dichloro-3-thenoyl)acetic acid esters 52 in the presence of a strong base. Esters 52 and products of their alkaline hydrolysis 56 have an antibacterial action the influence of the substituents on the biological activity of the resulting compounds was studied. 

C. G. Zhan, D. W. Landry and R. L. Orstein, Energy barriers for alkaline hydrolysis of carboxylic acid esters in aqueous solution by reaction field calculations, J. Phys. Chem. A, 104 (2000) 7672-7678. 

The Darzens reaction of isatin with ethyl chloroacetate yields glycidic esters. Alkaline hydrolysis of the glycidic esters yields indole-2,3-dicarboxylic and indole-3-carboxylic acids in a 6 1 proportion. The isolation of two isomeric glycidic esters, and the fact that both produce the indolecarboxylic acids in the same proportion led to a mechanistic proposal for the formation of the later through a common intermediate439 (Scheme 101). 

Derivatives of the 2-phenyl-1,3,4-oxadiazole-5-carboxylic acids give the usual reactions of acids on careful treatment.103 Thus the alcoholysis of the 5-acid chlorides with methanol or ethanol leads to the corresponding ester. Alkaline hydrolysis at 30° produces the carboxylic acid which on warming is decarboxylated to 2-phenyl-1,3,4-oxadiazole. Even a slight increase in the severity of the reaction conditions produces ring cleavage.103 The alkaline hydrolysis of 2-phenyl-5-(p-cyanophenyl)-1,3,4-oxadiazole with addition of H202 leads to 2-phenyl-5-(p-carboxamidophenyl)-1,3,4-oxadiazole.23... 

Thermal decarboxylation of l-methyl-2-oxo-l,2-dihydro-l,4,5-tri-azanaphthalene-3-carboxylic acid is accompanied by the formation of a red compound as a by-product, to which the dimeric structure 180b has been assigned.261 Acid or alkaline hydrolysis of the ethyl ester of the monomer yields the same dimer. 

Sulfur analogs of 5-oxo-3-pyrazolin-4-carboxylic acids, esters and amides are known. The usual synthesis of both thio and dithio acids is by alkaline hydrolysis of the dithioesters,109,831 as shown in eq. 234. 

Decarboxylation of the 3,6-diamino-2-carboxylic acid is readily achieved by heating with copper and quinoline. Simple heating above the melting point serves to decarboxylate various 3-oxo-2-carboxylic acids.During the decarboxylation of the acid 112 a red by-product was formed. This was also isolated from acid or alkaline hydrolysis of the ethyl ester of the acid 112. This product was formulated as 113 by analogy with indigo. A similar product was obtained from the 2-oxo-3-carboxylic acid. " ... 

Carboxylic acid ester, carbamate, organophosphate, and urea hydrolysis are important acid/base-catalyzed reactions. Typically, pesticides that are susceptible to chemical hydrolysis are also susceptible to biological hydrolysis the products of chemical vs biological hydrolysis are generally identical (see eqs. 8, 11,13, and 14). Consequendy, the two types of reactions can only be distinguished based on sterile controls or kinetic studies. As a general rule, carboxylic acid esters, carbamates, and organophosphates are more susceptible to alkaline hydrolysis (24), whereas sulfonylureas are more susceptible to acid hydrolysis (25). 

The first was proposed by Iraoto and Otsuji (511) and Otsuji et al (512) and concerned the pK of substituted 2-, 4-, and 5-carboxylic acids and the alkaline hydrolysis rate k of their respective ethyl esters (259, 260, and 261, where Y = Et). When Hammett cr , values were used for... 

In fact, most pyrimidinecarboxylic acids are made by hydrolysis of the corresponding esters, nitriles or sometimes amides, many of which can be made more easily by primary synthesis than can the acids themselves. Thus, pyrimidine-5-carboxylic acid may be made by alkaline hydrolysis of its ethyl ester (62JOC2264) and pyrimidin-5-ylacetic acid (789 ... 

Only in the case of the pyruvic acid condensation product was it possible to isolate the corresponding ethyl ester under these conditions. This, on mild hydrolysis, reverted to 1-methyl-1,2,3,4-tetrahydro-j8-carbohne-1-carboxylic acid, identical with the starting material, which therefore had the assigned structure 26 (R = CH3) and was not the SchiflF s base 25 (R = CH3). Alkaline hydrolysis of the ester was accompanied by decarboxylation. ... 

To set the stage for the crucial aza-Robinson annulation, a reaction in which the nucleophilic character of the newly introduced thiolactam function is expected to play an important role, it is necessary to manipulate the methyl propionate side chain in 19. To this end, alkaline hydrolysis of the methyl ester in 19, followed by treatment of the resulting carboxylic acid with isobutyl chlorofor-mate, provides a mixed anhydride. The latter substance is a reactive acylating agent that combines smoothly with diazomethane to give diazo ketone 12 (77 % overall yield from 19). 

Compared to the lithium enolates of l and 5, the higher stereoselectivity obtained by the Mukaiyama variation is, in general, accompanied by reduced chemical yields. The chiral alcoholic moieties of the esters 3 and 7 can be removed either by reduction with lithium aluminum hydride (after protection of the earbinol group) or by aqueous alkaline hydrolysis with lithium hydroxide to afford the corresponding carboxylic acid. In both cases, the chiral auxiliary reagent can be recovered. 

When a carbonyl group is bonded to a substituent group that can potentially depart as a Lewis base, addition of a nucleophile to the carbonyl carbon leads to elimination and the regeneration of a carbon-oxygen double bond. Esters undergo hydrolysis with alkali hydroxides to form alkali metal salts of carboxylic acids and alcohols. Amides undergo hydrolysis with mineral acids to form carboxylic acids and amine salts. Carbamates undergo alkaline hydrolysis to form amines, carbon dioxide, and alcohols. 

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