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A simple route to 2,3-benzodiazepines from substituted indenes
Ekaterina S Tarasova1, Olga V Shurupova1, Sergey A Rzhevskiy1
1A.V. Topchiev Institute of Petrochemical Synthesis, Russian Academy of Sciences, Leninsky Prospect 29, Moscow, 119991, Russia. aasachenko@ips.ac.ru.
Organic & Biomolecular Chemistry
|April 16, 2025
Summary
This study introduces a new two-step synthesis for 2,3-benzodiazepines from indenes. The method efficiently produces various compounds, including the anxiolytic tofisopam, with a detailed reaction mechanism elucidated.
Area of Science:
- Organic Chemistry
- Medicinal Chemistry
Background:
- 2,3-Benzodiazepines are a class of psychoactive compounds with significant pharmacological applications.
- Existing synthetic routes may lack efficiency or versatility for diverse substitutions.
Purpose of the Study:
- To develop an optimized, two-step synthetic strategy for 2,3-benzodiazepines starting from substituted indenes.
- To investigate the scope and limitations of the developed method for synthesizing a range of substituted 2,3-benzodiazepines.
- To elucidate the reaction mechanism of the key cyclization step.
Main Methods:
- Oxidation of substituted indenes to the corresponding 1,5-diketones.
- Cyclocondensation of 1,5-diketones with hydrazine hydrate under optimized conditions.
- Reaction mechanism investigation using 1H NMR kinetic experiments.
Main Results:
- Successful synthesis of various substituted 2,3-benzodiazepines, including tofisopam.
- Optimization of reaction conditions leading to high yields and purity.
- Detailed mechanistic insights into the cyclization process were obtained.
Conclusions:
- The presented two-step approach provides an efficient and versatile route to substituted 2,3-benzodiazepines.
- The study offers a valuable synthetic methodology for accessing pharmacologically relevant benzodiazepine derivatives.
- Mechanistic understanding facilitates further optimization and development of related synthetic strategies.
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