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Synthesis of 1,3,4‐thiadiazol‐2‐ylacetic acid derivatives
Author(s) -
Saito Toshinori,
Saheki Norio,
Hatanaka Minoru,
Ishimaru Toshiyasu
Publication year - 1983
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570200117
Subject(s) - chemistry , diethyl malonate , halogenation , nucleophile , organic chemistry , medicinal chemistry , catalysis
Abstract 1,3,4‐Thiadiazol‐2‐ylacetic acids 4 were prepared by lithiation of 2‐methyl‐1,3,4‐thiadiazoles 1 , followed by treatment with carbon dioxide. Diethyl 1,3,4‐thiadiazol‐2‐ylmalonates 6 were prepared by nucleophilic displacement reaction of the corresponding bromides 5 with diethyl malonate. Introduction of the amino group at the a‐position of 4 or 6 was carried out via oximation or bromination to give the amino ester 9 or 4 . Attempts to prepare DL‐α‐amino‐1,3,4‐thiadiazol‐2‐ylacetic acids from 9 or 4 were unsuccessful because the amino acids were decarboxylated too rapidly to be isolated in the free form.