2-methylalkanoic acid esterification

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]. 

Table 4.4 Resolution of 2-methylalkanoic acids by esterification in an organic solvent. In cases where immobilized CRL was used, it was immobilized on Accurel EP100 (350-1000 ) [136].

The resolution of 2-methylalkanoic acid by enzymatic esterification is quite efficient using a long-chained alcohol. ... 

Scheme 17 Candida rugosa lipase-catalyzed esterifications of 2-methylalkanoic acids [133, 134]. The E value is higher at a low concentration of alcohol.

SchGine 7 Resolution of racemic 2-methylalkanoic and -arylalkanoic acids by esterification. 

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