From 2-acetyl-indan-1,3-dione to 2H-1,5-benzodiazepines and their versatile applied features

TL;DR

This paper presents a new method to synthesize 2H-1,5-benzodiazepines from 2-acetyl-indan-1,3-dione, which are important compounds in pharmaceuticals for treating central nervous system disorders.

Contribution

A novel synthetic pathway for 2H-1,5-benzodiazepines using 2-acetyl-indan-1,3-dione and various benzaldehydes is introduced.

Findings

The reaction of 2-acetyl-indan-1,3-dione with benzaldehydes forms cinnamoyl derivatives.

These cinnamoyl derivatives further react with 1,2-diaminobenzene to produce 2H-1,5-benzodiazepines.

The solid-state structures of the precursors and final products were analyzed and discussed.

Abstract

Benzodiazepines (seven-membered heterocyclic compounds having two nitrogen atoms at different positions; BZDs) are ruling scaffolds in the area of the pharmaceutical industry for preparing various drugs having biological activity on central nervous system (antidepressant, anticonvulsant, muscle relaxant, anxiolytic, antiepileptic, hypnotic, and sedative functions). The most common synthesis of BZDs involves the condensation of o-phenylenediamine (OPD) with various carbonyl compounds (such as 1,3-dicarbonyls) in the presence of various catalysts or catalyst- free systems.

The reaction of 2-acetyl-1,3-indanedione (Scheme 1.; I) with various benzaldehydes (Scheme 1.; II) results in the cinnamoyl derivatives formation (Scheme 1; III) which upon condensation with 1,2-diaminobenzene (OPD) form the series of 2H-1,5-benzodiazepines.

(II: 1, benzaldehyde; 2, p-fluoro-benzaldehyde; 3, p-chloro-benzaldehyde; 4, p-methyl-benzaldehyde; 5, p-cyano- benzaldehyde; 6, p-methoxy-benzaldehyde; 7, p-dimethylamino-benzaldehyde)

Scheme 1. Reaction scheme from 2-acetyl-1,3-indanedione (I) to cinnamoyl derivatives (III) The solid-state structural features of the aforementioned precursors as well as of the 2H-1,5-benzodiazepine derivative (Scheme 1., Fig.1.) prepared by us, will be discussed.