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Quaternization of 2‐aziridino‐5‐chlorobenzophenone, an efficient synthesis of medazepam
Author(s) -
Mihalić M.,
Šunjić V.,
Kajfež F.,
Žinić M.
Publication year - 1977
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.5570140545
Subject(s) - chemistry , methanol , yield (engineering) , methyl iodide , iodide , medicinal chemistry , stereochemistry , organic chemistry , materials science , metallurgy
Quaternization of 2‐aziridino‐5‐chlorobenzophenone (1) with methyl iodide resulted in formation of 2‐( N ‐β‐iodoethyl‐ N ‐methyl)aminobenzophenone ( 2 ), via an unstable quaternary compound. Rate constants for 1 → 2 conversion, as determined by an nmr method at 35 ± 0.1°, varied between 0.22 × 10 −3 sec −1 in DMSO‐d 6 , and 0.95 × 10 −6 sec −1 in methanol‐d 4 . Ammonolysis with hexamine, and subsequent cyclization afforded 7‐chloro‐l‐methyl‐5‐phenyl‐2,3‐dihydro‐l H ‐1,4‐benzodiazepine (3, generic name medazepam) in 92% over‐all yield.