Solvent-Free Syntheses of 1,5-Benzodiazepines Using HY Zeolite as a Green Solid Acid Catalyst

Abstract

1,5-Benzodiazepines are synthesized from 1,2-diamines and ketones catalyzed by HY zeolite at 50 °C under solvent-free conditions. This process offers an easy and efficient synthesis of substituted 1,5-benzodiazepines in high yields. The advantages of this protocol are operational simplicity, nontoxicity, low cost, easy recovery, and an environmentally benign nature. The catalyst is recovered by filtration and reused six times without significant loss in its catalytic activity. A plausible mechanism is also proposed.

Enhanced Catalytic Properties of Carbon supported Zirconia and Sulfated Zirconia for the Green Synthesis of Benzodiazepines

“…Thus, when using 6a it was observed the exclusive formation of the corresponding benzodiazepine 7 in 76 %, after 3 h of reaction time, as unique reaction product, and in good agreement with data previously reported using other catalytic systems (Figure ); in this case, the lower conversion values are attributed to the steric hindrance of the corresponding carbonyl compound regarding to acetone 3 . On the other hand, the reaction in the presence of ethyl acetoacetate 6b led to the total transformation of o ‐phenylendiamine 2 yielding a mixture of the intermediate 8 , resulting of the imination reaction between reagents and subsequent tautomerization, and of 2‐methylbenzoimidazole 9 (compounds 8/9 ratio=77 : 23 after 15 min of reaction time), instead of the corresponding benzodiazepine.…”

“…1 H chemical shifts in [D 6 ]DMSO are referenced to internal tetramethylsilane. Characterization data of benzodiazepines 1 and 7 and 2‐methyl benzoimidazole 9 are in good agreement with those previously reported using other catalytic systems ,…”

“…[10,11] Benzodiazepines are considered as relevant nitrogen heterocyclic systems and their importance is related to diverse pharmacological activities: anti-inflammatory, antiviral, analgesic, anti-microbial, sedative, hypnotic, anti-depressive, anti- tumor, anti-HIV, and also effective on cardiovascular disorders, etc. [12] Different homogeneous catalysts, mainly consisting of metal transition salts, and also heterogeneous ones, operating under a great variety of reaction conditions have been applied in the synthesis of benzodiazepines from o-phenylendiamine and ketones [13] Among the most important heterogeneous catalytic systems, it can be cited: zeolites, Al-MCM-41 and Cu(BDC), [14] H-MCM-22, [15] SiO 2 supporting H 2 SO 4 [16] and HClO 4 , [17] clays [18][19][20] and even SZ. [21] The goal of this paper is, therefore, to perform a comparative study of Zr and SZr catalytic properties with those found for supported carbon with Zr and SZr.…”

Synthesis of 2,2,4-Trimethyl-2,3-dihydro-1H-1,5-benzodiazepine using Treated Natural Zeolite Catalyst

“…This 1,5-Benzodiazepine, an important class of biologically active N-containing heterocyclic compound, shows various pharmacological properties for example antidepressive, antiallergic, antiinflammatory, antipyretic, analgesic, anticonvulsant, hypnotic, antianxiety, antiulcerative, antihistaminic [1]. Along with the appliances in medical treatment such as cardiovascular diseases, schizophrenia, and cancer [2,3], the application of 1,5 benzodiazepine de-in some cases, homogenous catalysts have some limitations such as difficult to remove from the reaction mixture, unrecyclable, requiring tedious workup procedures for the elimination of transition metal contaminants from the synthesized product which thus causing a concern to ecological and economic issues [15][16][17]. These problems have led some researchers to focus on synthesizing 1,5-benzodizepine and its derivatives through green chemical processes, i.e.…”

“…These problems have led some researchers to focus on synthesizing 1,5-benzodizepine and its derivatives through green chemical processes, i.e. performing the reaction under solvent-free condition and developing heterogeneous catalyst [15].…”