Alumina/Phosphorus Pentoxide (APP) as an Efficient Reagent for the Synthesis of 1,5-Benzodiazepines under Microwave Irradiation

Abstract

Alumina-supported phosphorus pentoxide was found to be an efficient reagent for the synthesis of 1,5-benzodiazepine derivatives from phenylenediamine and ketones in the solvent-free condition under microwave irradiation. This method is an easy, rapid, and high-yielding reaction for the synthesis of 1, 5-bezodiazepines.Heterocyclic compounds hold a special place among pharmaceutically important natural and synthetic materials. The remarkable ability of heterocyclic nuclei to serve both as biomimetics and active pharmacophores has largely been contributed to their unique value as traditional key elements of numerous drugs. 1 The benzodiazepine nucleus is a well-studied traditional pharmacophoric scaffold that has emerged as a core structural unit of various sedative hypnotic, muscle relaxant, anxiolytic, antistaminic, and anticonvulsant agents. 2 Although the first benzodiazepine was introduced as a drug nearly 30 years ago the research in this area is still very active and is directed toward the synthesis of compounds of enhanced pharmacological activity. Several methods, not generally applicable, have been reported in the literature for synthesis of 1,5-benzodiazepines. 3-7 Unfortunately, many of these processes suffer limitations, such as drastic reaction conditions, low yields, tedious work-up procedures and cooccurrence of several side reactions. Recently we found that the mixture of magnesium oxide with phosphorus oxychloride is a new reagent for the synthesis of 1,5-benzodiazepines. 8 However, treatment

Thermal decomposition of ethylenediaminetetraacetic acid in the presence of 1,2-phenylenediamine and hydrochloric acid

“…Although the rearranged intermediates have not been directly detected in the EDTA decomposition, some potential fragments can still be proposed. It is reported that compound 1 could be prepared by condensation of o-PDA with 4-methyl-3-penten-2-one, 25 acetone, [26][27][28][29][30][31] acetonedicarboxylic acid, 32 or 2, 4, 4-trichloro-2-metylpentane 33 under different conditions ( Figure 5). These facts suggest that the rearranged intermediates might be one or some of these reactants.…”

“…[38][39][40][41][42] Several methods for preparing these compounds have been reported in the literature. [25][26][27][28][29][30][31][32] To our knowledge, the formation of the 1,5-benzodiazepine skeleton by the reaction of EDTA with o-PDA in strong acidic medium has not been reported so far. Although this reaction may not be an economic route for the preparation of compound 1, it helps us to sketch a new potential thermal decomposition mechanism for EDTA.…”

Two Step One-Pot Synthesis of Novel 5-(4-Fluorophenyl)-1<i>H</i>-Beno[e][1,4]Diazepin-2(3<i>H</i>)-One and it’s Base Catalyzed Transformation to <i>N</i>-Alkyl and C-3 Arylidene Derivatives

“…Owing to their versatile applications, various methods for the synthesis of benzodiazepines have been reported in the literature. These include condensation reactions of o-phenylenediamines with α,β-unsaturated carbonyl compounds [9] in the presence of various kind of catalysts [10][11][12][13][14][15][16][17][18] . The most extensively used methods for preparing 1,4-benzodiazepines begins with an 2-aminobenzophenone.…”

Sodium tetrachloroaurate(III) dihydrate-catalyzed efficient synthesis of 1,5-benzodiazepine and quinoxaline derivatives

“…To date, several methods for the preparation of 1,5-benzodiazepines have been reported in the literatures, including condensation reactions of o-phenylenediamine with α,β-unsaturated carbonyl compounds (Ried and Stahlofen, 1957), β-haloketones (Ried and Torinus, 1959) or ketones promoted by BF 3 ·Et 2 O (Herbert and Suschitzky, 1974), NaBH 4 (Morales et al, 1986), polyphosphoric acid or SiO 2 , (Jung et al, 1999), MgO/POCl 3 (Balakrishna and Kaboudin, 2001), Yb(OTf) 3 (Curini et al, 2001), Al 2 O 3 /P 2 O 5 or AcOH under microwave (Kaboudin and Navaee, 2001), ionic liquid (Jarikote et al, 2003), SmI 2 (Luo et al, 2005), HBF 4 -SiO 2 (Bandgar et al, 2006), dodecyl sulfonic acid (Sharma et al, 2007), AgNO 3 (Kumar et al, 2006) (Heravi et al, 2007a), polyanilinesulfate salt (Srinivas et al, 2007), and 2,4,6-trichloro-1,3,5-triazine (Kuo et al, 2008). Meanwhile, a number of methods have also been developed for the synthesis of quinoxalines, involving condensation of 1,2-diamines with 1,2-dicarbonyl compounds (Kaupp and Naimi-Jamal, 2002;More et al, 2005;Bhosale et al, 2005;Heravi et al, 2007b), 1,4-addition of 1,2-diamines with 1,2-diaza-1,3-butadienes (Aparicio et al, 2006), oxidation-trapping of α-hydroxy ketones with 1,2-diamine (Raw et al, 2004;Kim et al, 2005;Robinson and Taylor, 2005), cyclization-oxidation of polymer-linked 2-nitrophenyl carbamate with α-bromo ketones (Singh et al, 2003), and oxidativecoupling of epoxides with o-phenylenediamine (Antoniotti and Duñach, 2002).…”