Reaction of amino-acid esters with sodium in liquid ammonia: cleavage of the proline ring

Abstract

The reduction of esters by sodium in liquid ammonia solutions has been investigated in some detail by Kharasch et al.. From an analysis of the products obtained, it was concluded by these authors that aliphatic esters were converted to a mixture of the corresponding alcohol, amide and acid, in addition to varying amounts of unidentified substances. There have been very few investigations of the reaction of amino-acid esters with sodium in liquid ammonia solutions. McChesney and Miller treated glycine ethyl ester hydrochloride with sodium in liquid ammonia and obtained some of the glycine ester and an unidentified product. Benzyl esters of amino-acids and peptides are known to be cleaved to form the corresponding amino-acid or peptide. With the availability of the t-butyloxycarbonyl group for masking ammo functions and the t-butyl group for protecting carboxyl groups and hydroxyl groups, it became important to know whether these groups were resistant to the reductive action of sodium in liquid ammonia. This treatment readily removes other protecting groups such as the p-toluene sulphonyl and the carbobenzoxy groups. Anderson and McGregor found that the t-butyloxy-carbonyl group is resistant to treatment with sodium in liquid ammonia. The effects of this reductive treatment on amino-acid and peptide t-butyl esters have been investigated. Results of the reaction of proline t-butyl ester with sodium in liquid ammonia are presented here.