A Study of Some 2,3-Dioxopyrrolidines and Derived Bipyrrolidines¹

Abstract

A one-step procedure is described for the preparation of l-substituted-4-carbethoxy-2,3-dioxopyrrolidines from ethyl acrylate, a primary aliphatic amine, and ethyl oxalate as starting materials. Three of the products so obtained have been acetylated to yield 3-acetoxy-4-carbethoxy-2-oxo-3-pyrrolines, and seven have been hydrolyzed and decarboxylated to yield l-substituted-2,3-dioxopyrrolidines. Among the latter substances four have been reduced to 3-hydroxy-2-oxopyrrolidines and two further reduced to 3-hydroxypyrrolidines. All of these conversions can be achieved in fair to good yield and may be considered of preparative value.The l-substituted-2,3-dioxopyrrolidines are readily converted into a variety of derivatives by reaction with carbonyl reagents. They also undergo self-condensations of the aldol type with great facility to yield products which contain the 3,3 '-bipyrrolidine system.Recent investigations in this laboratory have led to the development of a new and convenient method of synthesis for 4-carboalkoxy-2,3-dioxopyrrolidines (I) from readily available starting materials. The method is based upon the condensation of alkyl HO-G=C-C02C2H6 !

Synthetic approaches and pharmaceutical applications of chloro-containing molecules for drug discovery: A critical review

“…In 2018, Hangeland and co-workers synthesized potent lipase inhibitors from starting material Ethyl 1-ethyl-4-hydroxy-5-oxo-2,5-dihydro-1H-pyrrole-3-carboxylate 356 [121,122]. Compound 356 was first o-methylated with trimethylsilyldiazomethane in the presence of DIPEA [123], followed by saponification of the ester.…”

Some pyrrolidone derivatives

“…identical with a sample prepared according to Southwick et al (6). he nitrile hydrolysis may follow the same course as that outlined recently by Stephenson et al (7).…”

“…he nitrile hydrolysis may follow the same course as that outlined recently by Stephenson et al (7). Several investigators (4)(5)(6)8) have reported on the keto-en01 tautomerism of pyrrolidine-2,3-diones. The presence of a 4-substituent is stated to result in complete enolization as estimated from n.m.r.…”

Pyrrolidine‐2,3‐diones: Synthesis, reactions and biological activity

“…The most convenient method for the synthesis of 1‐substituted‐4‐carboethoxypyrrolidine‐2,3‐diones ( 11 ) is based upon the condensation of dimethyl or diethyl oxalate with N ‐alkyl or N ‐aryl‐ β ‐aminopropionic acid esters ( 10 ), in the presence of sodium alkoxides 8,17,18,19,20,21,22 (Scheme 3).…”