Carboxylic acid derivatives esterifications

In studies directed towards the synthesis of pseurotin A, the unsaturated acetal 3 has been used as a common starting material to prepare two different C-2-branched intermediates. In one route, 3 was 0-benzylated, the aldehyde im-masked with hydrochloric acid and oxidized to its carboxylic acid derivative. Esterification, dihydroxylation of the alkene then dimethylsulfoxide-thionyl chloride oxidation, addition of ethylmagnesium chloride and removal of the isopropylidene group gave compounds 4. In an alternative route, 3 was first epoxidized then treated sequentially with hydroxide, benzyl bromide-base and hydrochloric acid to give compounds 5. ... 

As noted in the preceding section, one of the most general methods of synthesis of esters is by reaction of alcohols with an acyl chloride or other activated carboxylic acid derivative. Section 3.2.5 dealt with two other important methods, namely, reactions with diazoalkanes and reactions of carboxylate salts with alkyl halides or sulfonate esters. There is also the acid-catalyzed reaction of carboxylic acids with alcohols, which is called the Fischer esterification. 

There are several examples of dehydrations of chemicals derived by renewable resources by use of heteregeneous catalytic approaches in the literature. These can be categorized into three types of reactions (a) reactions in which one (or more) molecule(s) of water is eliminated from a single substrate molecule, (b) reactions in which one (or more) molecule(s) of water is generated as the result of an esterification reaction between an alcohol and a carboxylic acid or carboxylic acid derivative and (c) reactions in which one (or more) molecule(s) of water is generated due to an etherification reaction between two alcohol functionalities. 

Generally pyrazolo[4,3-d]pyrimidines are prepared from pyrazole-5-carboxylic acid derivatives 180 via nitration to yield 181, which on esterification and reduction affords 184 (72CCC2786 78M11 79BCJ208 80MI35 ... 

The most important reactions of carboxylic acids are the conversions to various carboxylic acid derivatives, e.g. acid chlorides, acid anhydrides and esters. Esters are prepared by the reaction of carboxylic acids and alcohols. The reaction is acid catalysed and is known as Fischer esterification (see Section 5.5.5). Acid chlorides are obtained from carboxylic acids by the treatment of thionyl chloride (SOCI2) or oxalyl chloride [(COCl)2], and acid anhydrides are produced from two carboxylic acids. A summary of the conversion of carboxylic acid is presented here. All these conversions involve nucleophilic acyl substitutions (see Section 5.5.5). 

For most cases, common fluoroacyl derivatives are sufficiently reactive and selective Thus conversion of perfluoroglutaric dichloride to a monomethyl ester by methanol proceeds smoothly under the appropriate reaction conditions [17] (equation 9) Perfluorosuccinic acid monoester fluoride, on the other hand, is prepared most conveniently from perfluorobutyrolacetone [IS] (equation 10) Owing to the strong acidity of a fluonnated carboxylic acids, Fischer esterification with most aliphatic alcohols proceeds autocatalytically [79 20]... 

This procedure offers a convenient method for the esterification of carboxylic acids with alcohols2 and thiols2 under mild conditions. Its success depends on the high efficiency of 4-dialkylaminopyridines as nucleophilic catalysts 1n group transfer reactions. The esterification proceeds without the need of a preformed, activated carboxylic acid derivative, at room temperature, under nonacidic, mildly basic conditions. In addition to dichloromethane other aprotic solvents of comparable polarity such as diethyl ether, tetrahydrofuran, and acetonitrile can be used. The reaction can be applied to a wide variety of acids and alcohols, including polyols,2 6 a-hydroxycarboxylic acid esters,7 and even very acid labile... 

Esters are carboxylic acid derivatives in which the hydroxyl group (—OH) is replaced by an alkoxy group (—OR). An ester is a combination of a carboxylic acid and an alcohol, with loss of a molecule of water. We have seen that esters can be formed by the Fischer esterification of an acid with an alcohol (Section 20-10). 

A particularly attractive starting material is the homochi-ral carboxylic acid derivative, obtained by conventional resolution. Esterification and then simple amine addition and oxidative decomplexation produces a precursor of (—)-gabacuUne (Scheme 33). 

Formation of Esters. One frequently used approach to the formation of diastereomeric derivatives of carboxylic acids is esterification with an optically active alcohol (Eq, 9)... 

Obtained by exposure of the carboxylic acid derived from the Claisen rearrangement to the esterification conditions (OH, OH,SOCl,), resulting in loss of the MOM protecting group. 

A review of the synthesis and chemistry of nitroxide spin labels includes a number of steroid derivatives. Novel spin-labelled steroids have been prepared by esterification with the nitroxyl carboxylic acid derivative (17),for use in spin immunoassays (SIA) as an alternative to radioactive labelling. The prednisolone ester (18), for example, exhibits an e.s.r. spectrum with narrow lines when it is in a free state in solution, but when bound to antibody the rate of tumbling is reduced, and linewidths are broad. Signals from bound and unbound derivatives are easily distinguished and measured, so SIA of antibody-bound prednisolone provides a potentially useful serum assay method. 

The most frequently used approaches for derivatizing carboxylic acids are esterification with a variety of single-enantiomer alcohols, or formation of amides with single-enantiomer amines [234,252]. The formation of amide derivatives requires activation of the carboxylic acid by formation of the acid chloride with thionyl chloride, mixed anhydrides with chloroformates, N-acylimidazoles with 1,1 -carbonyldiimidazole or N-acylureas with dicyclohexylcarbodiimide. Esterification reactions generally re-... 

Acyl Isethionates are ester-type anionic surfactants formed by monocarboxylic acids and isethionic acid HOCH2CH2SO3H. The latter is formed by reaction of 30 % aqueous sodium bisulphite and ethylene oxide at 70 C [66]. All commercial isethionates (as sodium cocoyl isethionate) are esters derived from natural carboxylic acids by esterification of the acids or acyl chlorides with sodium isethionate ... 

The carboxylation of optically active a-lithiated-a, 3-unsaturated sulfoxides has been reported. For example, Posner and coworkers have performed a one-pot a-lithiation followed by carboxylation and esterification of the a,p-unsaturated sulfoxide (58) to give enantiomerically pure a-methoxycarbonyl-a,P-unsaturated sulfoxide (59) in 80% yield (Scheme 5.19) [52,58]. Protonation rather than methylation leads to the corresponding carboxylic acid in >95% yield. This methodology has been utilized in the synthesis of enantiomerically pure (5)-(-i-)-2-(p-tolylsulfinyl)-2-buten-4-olide (62) from the a,P-unsaturated sulfoxide (6()) via the carboxylic acid derivative (61) (Scheme 5.19) [59]. An efficient route to nonracemic 2-(p-tolylsulfinyl)-2-buten-4-olides employing carboxylation of an a-lithio-a,p-unsaturated sulfoxide has also been developed by Holton and Kim [60]. 

Carbonyl addition-elimination n. The single most important type of reaction mechanism which has been applied to the preparation of step-growth polymers is the addition-elimination reaction of the carbonyl double bond of carboxylic acids and carboxylic acid derivatives included in this general type of reaction are esterification amidation and anhydride formation from carboxylic acids, esters, amides, anhydrides and acid halides. 

Carboxylic acid esters of xylan are prepared under typical conditions used for polysaccharide esterification, i.e., activated carboxylic acid derivatives are allowed to react >vith the polymer both heterogeneously and homogeneously (Figure 1). The heterogeneous esterification of oakwood sawdust and wheat bran... 

The reaction of a carboxylic add with a phenol (Section 19-9) to form a phenyl ester is endothermic. Therefore, esterification requires an activated carboxylic acid derivative, such as an acyl halide or a carboxyUc anhydride. 

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