Alkanoic acids, esterification

XRD samples 638 f alignment defects, displays 756 alignment materials, displays 732 aliphatic chains 125,395 alkanes, solvents 883 alkanoic acids, esterification alkanols, esterification 106 alkenes, solvents 883 alkenyl, terminal substituents alkyl functionalization, arenes alkyl groups... 

Most aliphatic acid.s enter the process easily, but more vigorous reaction conditions are necessary for aryl carboxylic acids or for sterically hindered alkanoic acids. Increased pressure can help counteract such problems, e.g. 2,2-dimethylpropanoic acid heated at 112°C in ethanol with o-phenylenediamine dihydrochloride for 24 h at 8kbar pressure gives a 48% yield of 2-l-butylbenzimidazolc 76. Care has to be taken, though, that the ethanol concentration is not too high, as esterification of the carboxylic acid becomes a competing reaction DMSO appears to be a suitable alternative... 

The direct esterification reaction (Scheme 6) has found many applications in organic synthesis, although the esterification is in competition with the reverse reaction of hydrolysis [73]. The esterifications are more conveniently performed in nonaqueous media in order to displace the equilibrium in favor of the synthesis. In this case, parameters such as the amount of water and the nature of organic solvents have to be carefully considered [74]. Several 2-methyl alkanoic acids can be resolved using esterification with alcohols of various chain length, in the presence of various lipases (Scheme 7) such as immobilised C. antarctica lipase (more than 95% e.e. for both unreacted acid and ester) [75], C. rugosa lipase in cyclohexane 913% e.e. for the ester and 78% e.e. for the acid) [76], crosslinked C. r go5 a lipase in heptane (99.5% e.e. for the ester and 89.4% e.e. for the acid) [77]. In some cases, the alcohol that reacts with the acid is the solvent of the reaction [76], but the esterification process may be carried out in organic solvents [75,77]. 

Resolution of branched alkanoic adds. Hydrolase-catalyzed esterification of 2-methylalkanoic acids can be fairly efficient, especially for acids with long chains, provided that the conditions are carefully adjusted by immobilization of the enzyme (in some cases), by control of the water activity, and by proper choice of the appropriate alcohol as nucleophile as well as the correct solvent [134]. The alcohol concentration does also influence the E-value [133]. It is important to note that the esterifications are reversible, thus preventing easy access to the remaining substrate in high ees. Some representative examples are given in Table 4.4. A procedure based on iterative resolutions can be used to provide both enantiomers of 2-methyloctanoic acid in high ees (>99%) and reasonable yields (25% for S- and 43% for R-acid based on the starting racemic acid) [137]. 

Esterification of glycerol with acids 324a-324e provided a series of mono-, di- and trisubstituted triacylglycerols (325) in 70-99% radiochemical yields labelled with 125I, Cholesteryl-c< -(3-amino-2,4,6-triiodophenyl)alkanoates have been 125I-labelled in pivalic acid, also in high 94-98% yields. 

Another class of esterification reagents are halogenated compounds (alkyl iodides, substituted benzyl, and phena-cyl bromides), which need basic media for their reaction [K2CO3 or DMFA (dimethyl formamide) is normally used for the neutralization of HHal as acid by-product]. For methy-lation of carboxylic acids, some tetra-substituted ammonium hydroxides or halides can be used, e.g., tetramethylammo-nium hydroxide (in aqueous solutions) or trimethylanilinium hydroxide (in methanol solution). The intermediate ammonium carboxylates are thermally unstable and produce methyl alkanoates when the reaction mixtures are heated or when the carboxylates are introduced into the hot injector of the gas chromatograph (flash or on-column methylation) ... 

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