Synthesis of 5-Amino-2-pyrrolidinone and Its Derivatives

Abstract

Two routes to a new type of 2-pyrrolidinones having various nitrogen functions at the 5-position were described.The modified Curtius reaction of pyroglutamic acid derivatives(& and -4 ) with diphenylphosphoryl azide(DPPA) gave 5-alkoxycarbonylamino-2-pyrrolidinones(2 and e) in one step.Furthermore, the substitution reaction of 5-ethoxy-2-pyrrolidinone(12) with nucleophiles(amines, carbamates, amide, indole, and diethylaniline) was found to be a preferable synthetic method to 5-substituted-2pyrrolidinones(z, 14, 15, and 16).The synthesis of 5-amino-2pyrrolidinone(8). a simple one, was also mentioned.A s a series of studies on the chemistrv of 2-pyrrolidinones1', we are now interested in the synthesis of 2-pyrrolidinones having nitrogen functions such as amino, amide, or carbamate groups at the 5-position, since few attempts to synthesize 5-amino-2-pyrrolidinones.especially having no substituent at the 1-position (naked NH), have been reported, and 5-amino-2-pyrrolidinones would be expected to have pharmacological activities.In this paper, we wish to n report a convenient synthesis of 5-amino-2-pyrrolidinones starting with pyroglutamic acid derivatives or with succin-H imide. 5-Amino-2-pyrrolidinonesOur initial studies were with the Curtius type rearrangement of pyroglutamic acid derivatives.Shioiri et a1.2) reported that the reaction of N-benzoxycarbonylproline with diphenylphosphoryl azide(DPPA) in the presence of carbamate gave the rearrangement product(L) in good yield.This modified Curtius reaction involved