Reductions of Carboxylic Acids and Esters with NaBH₄ in Diglyme at 162°C

Abstract

Aromatic esters, including the extremely sterically hindered ester: t-amyl 2-chlorobenzoate, are readily reduced to the corresponding benzyl alcohols in high yield with NaBH₄ in refluxing diglyme (162°C). In sharp contrast, aliphatic esters usually gave only low yields of alcohols. Instead, diglyme fragmentation products are formed which undergo transesterification reactions, producing complex product mixtures including products such as RCOOCH₂CH₂OCH₃. The mechanism of this process involves sodium borohydride-induced S_N2 cleavage of diglyme (hydride attack) at high temperatures. However, when the extremely electron rich, 3,4,5-trimethoxybenzoic acid is treated with NaBH₄/diglyme at 162°C (with or without an equivalent of LiCl), no 3,4,5-trimethyoxybenzyl alcohol is formed. The electron rich and hindered ester, t-amyl-3,4,5-trimethoxybenzoate, also does not reduce under these conditions (with or without LiCl). However, both methyl and isopropyl 3,4,5-trimethoxybenzoate esters were converted into 3,4,5-trimethyoxybenzyl alcohol in good yields in NaBH₄/diglyme/LiCl at 162°C. These reductions did not occur unless LiCl was present, illustrating the electron releasing effect of the three methoxy functions which reduce the carbonyl group's reactivity.

Keywords:

• Sodium borohydride
• Reductions
• Diglyme
• Transesterification
• Carboxylic acids
• Esters

Acknowledgments

The work was supported, in part, by the Morton Division of Rohm and Haas and the Grant Division of Ferro Corp.