1,5-Benzodiazepine derivatives were synthesized by the condensation reactions of
The synthesis of 1,5-benzodiazepines and their derivatives have attracted considerable attention of researchers, including pharmaceutical and organic synthetic chemists, in recent years because of their medicinal properties namely antianxiety, hypnotic, antidepressive, tranquilizing, antiinflammatory, anticonvulsant, antifeedant, antibacterial, and analgesic agents [
Due to their wide range of pharmacological activities and industrial and synthetic applications, the development of practical and green protocols continues to be a challenging endeavour in synthetic chemistry. In recent years, many methods for their preparation are reported in the literature. These include condensation reactions of
Bismuth (III) salts have emerged in the recent years as “eco-friendly” reagents suitable for green chemistry. They have received considerable attention as mild Lewis acids [
Thus, considering the advantages and applications of bismuth (III) salts and ionic liquid, and as part of our ongoing project to explore the catalytic activities of bismuth (III) salts in organic transformations [
In order to investigate the catalytic efficiency of bismuth (III) salts and compare it with different acid catalysts, the condensation of
Influence of catalysts on preparation of 1,5-benzodiazepines from o-phenylendiamine and acetonea.
Entry | Catalyst | Time | Yieldb |
---|---|---|---|
1 | — | 20 h | trace |
2 | HCl | 3 h | 79 |
3 | SiO2 | 3 h | 91 |
4 | YbCl3 | 1.5 h | 85 |
5 | [HMIm]BF4 | 3 h | 43 |
6 | Amberlyst-15 | 3.5 h | 90 |
7 | Polyphosphoric acid | 3 h | 83 |
8 | Bismuth (III) salts | 1 h | 95 |
aReaction condition:
The results mentioned in Table
Encouraged by the results obtained in the above reaction and in order to prove the generality and scope of this new protocol, a wide verity of ketones were evaluated and the results are summarised in Table
Bismuth (III) salts catalysed condensation of
Entry | Ketone | Product | Yielda | Mp (°C) |
---|---|---|---|---|
1 | Acetone | 95 | 125 | |
2 | 2-butanone | 90 | 137 | |
3 | 2-pentanone | 89 | 140 | |
4 | 3-pentanone | 92 | 143 | |
5 | 4-methyl-2-pentanone | 91 | 118 | |
6 | 3-methyl-2-butanone | 93 | 119 | |
7 | Cyclopentanone | 94 | 135 | |
8 | Cyclohexanone | 88 | 138 | |
9 | Acetophenone | 89 | 151 |
aReaction conditions:
Further, we extended this protocol to substituted
In conclusion, we have demonstrated here a new and efficient procedure for the synthesis of 1,5-benzodiazepine derivatives catalyzed by bismuth (III) salts in ionic liquid. The advantages of our protocol are easy workup, fast reaction rate, and mild reaction condition with good yield, which make the method an attractive and a useful contribution to the present methodologies.
All commercial reagents were used as received without purification, and all solvents were reagent grade. The reaction was monitored by TLC using on 0.25 mm E-Merck silica gel 60 F254 precoated plates, which were visualized with UV light. Melting points were taken in open capillaries. The IR spectra were recorded on a PerkinElmer 257 spectrometer using KBr discs. 1H NMR and 13C NMR spectra were recorded on a VXR-300 MHz instrument using TMS as an internal standard.
A mixture of
3290 (NH), 1642 (C=N), 1592 (Ar) cm−1; M+ 188. Mp 125 °C.
The authors greatly appreciate the financial support of University Grand Commission, New Delhi, and University of Mumbai. They are thankful to Dr. S. T. Gadade, Principal, C. K. Thakur College, for their generous support.