Syntheses and CD Studies of New Optically Active Substituted 1,5-Benzodiazepine Derivatives

✍ Scribed by Malik, Farnaz ;Hasan, Mashooda ;Khan, Khalid Mohammed ;Perveen, Shahnaz ;Snatzke, Günther ;Voelter, Wolfgang ;Duddeck, Helmut

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 955 KB
• Volume: 1996
• Category: Article
• ISSN: 0947-3440
• DOI: 10.1002/jlac.199619960121

✦ Synopsis

Abstract

Seventeen optically active substituted 1,3,4,5‐tetrahydro‐2__H__‐1,5‐benzodiazepine‐2‐thiones (1a to 1d, 2a to 2d, 3d to 3d, 4b to 4d and 5b to 5d) were synthesized by treating the corresponding optically active substituted 1,3,4,5‐tetrahydro‐2__H__‐1,5‐benzodiazepin‐2‐ones with Lawesson's reagent (L. R.). The thioamide 1a was alkylated with methyl iodide to obtain 4‐methyl‐2‐methylmercaptodihydro‐1,5‐benzodiazepine (6a) and 4,5‐dimethyl‐2‐methylmercaptodihydro‐1,5‐benzodiazepine‐2‐thione (6b). Twelve optically active substituted 1,3,4,5‐tetrahydro‐2__H__‐1,5‐benzodiazepines (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‐2__H__‐1,5‐benzodiazepin‐2‐ones. 4‐Methyl‐1,5‐diacetyl‐(7e) and 1,4,5‐trimethyl‐ (7d), 1,3,4,5‐tetrahydro‐2__H__‐1,5‐benzodiazepines were synthesized by treating 7a with acetic anhydride and methyl iodide separately as given in the experimental 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 → π* transition can be detected via the chiroptical methods only. Sign changes of Cotton effects upon N‐5 methylation strongly suggest a conformational change of the 7‐membered ring.