J. Knabe et S. Bender, 1,5-BENZODIAZEPINES, .1. RACEMATES AND ENANTIOMERS OF 3,3-DIALKYL-1,5-BENZODIAZEPINE-2,4-DIONES - SYNTHESIS, CONFIGURATION, AND ENANTIOMERIC PURITY, Archiv der pharmazie, 326(9), 1993, pp. 551-558
The syntheses of the rac. and the enantiomeric 3,3-dialkyl-1,5-benzodi
aze-pine-2,4-diones 1-3 were performed as shown in Scheme 5, starting
from 4- resp. 5-chloro-2-nitro-N-methylaniline (10/11) and the rac. or
enantiomeric dialkylcyanoacetic acid chlorides 6a/6b. The enantiomers
of ethylmethylcyanoacetic acid (5a) are known. From butylmethylcyanoa
cetic acid (5b) the (S)-(-)-enantiomer was obtained using codeine as r
esolving agent. By ring closure of 14/15 the benzodiazepines 16/17 wer
e obtained, but the main products were the benzimidazoles 18/19. The y
ield of 16/17 could be increased to 62-80 % when the conditions of the
reaction were modified. The N-phenylation of 16/17 according to a mod
ified Ullmann reaction gave the rac. and the enantiomeric 1,5-benzodia
zepines 1-3 in high yields. - The absol. configurations of the new ena
ntiomeric compounds are compiled in Tab. 1. The enantiomeric purities
(e/e) of the 1,5-benzodiazepines 1 and 3 and of all intermediates are
> 95 %. The enantiomeric purities of (R)-(-)-2 and the corresponding i
ntermediates were not determined.