SYNTHESES AND CD STUDIES OF NEW OPTICALLY-ACTIVE SUBSTITUTED 1,5-BENZODIAZEPINE DERIVATIVES

Seventeen optically active substituted 1,3,4,5-tetrahydro-2H-1,5-benzo diazepine-2-thiones (1a to 1d, 2a to 2d, 3b to 3d, 4b to 4d and 5b to 5d) were synthesized by treating the corresponding optically active su bstituted 1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-ones with Lawesson 's reagent (L. R.). The thioamide la was alkylated with methyl iodide to obtain -methyl-2-methylmercaptodihydro-1,5-benzodiazepine (6a) and -methylmercaptodihydro-1,5-benzodiazepine-2-thione (6b). Twelve optica lly active substituted 1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (7a to 7c, 8a to 8d, 9a to 9d and 10d) were synthesized by the reduction of the corresponding substituted 1,3,4,5-tetrahydro-2H-1,5-benzodiazepin- 2-ones. 4-Methyl-1,5-diacetyl- (7e) and 1,4,5-trimethyl- (7d), 1,3,4,5 -tetrahydro-2H-1,5-benzodiazepine were synthesized by treating 7a with acetic anhydride and methyl iodide separately as given in the experim ental part. The UV and CD spectra of the parent chiral benzodiazepines 7a to 7d and benzodiazepine-2-thiones 1a to 1d are discussed, showing that especially several n --> pi transitions can be detected via the chiroptical methods only. Sign changes of Cotton effects upon N-5 met hylation strongly suggest a conformational change of the 7-membered ri ng.