Divergent Regioselective Synthesis of 2,5,6,7-Tetrahydro-1H-1,4-diazepin-2-ones and 5H-1,4-Benzodiazepines

Abstract

A novel and simple one-pot synthesis of 3-substituted 2,5,6,7-tetrahydro-1H-1,4-diazepin-2-ones from 1,2-diaza-1,3-dienes (DDs) and N-unsubstituted aliphatic 1,3-diamines is described. Here we also report a procedure to selectively obtain alkyl 5H-1,4-benzodiazepine-3-carboxylates from the DDs and 2-aminobenzylamine. Both processes occur by means of sequential 1,4-conjugated addition followed by regioselective 7-exo cyclization. The behavior of N-methyl- and N,N'-dimethyl-1,3-diaminopropanes toward the DDs furnished pyrazol-3-ones and bis-α-aminohydrazones, respectively.

Transition metal-free one-pot synthesis of nitrogen-containing heterocycles

“…As an extension to their study on 1,2-diaza-1,3-dienes, Crescentini et al [261] have reported the divergent behavior of two different nucleophilic substrates toward 1,2-diaza-1,3-dienes (DDs) in the synthesis of 1,4-diazepines from DDs and 2-aminobenzylamine 447 or N-unsubstituted aliphatic1,3-diamines 448 via 1,4-conjugate addition and exo-cyclization. When DDs were treated with aliphatic 1,3-diamines in alcohol, the corresponding 3-substituted 2,5,6,7-tetrahydro-1H-1,4-diazepin-2-ones 449 were obtained, and when 1,3-diamines were employed in ethyl acetate, 5H-1,4-benzodiazepine-3-carboxylates 450 were furnished in overall good yields.…”

Expedient Synthesis of 1,4‐Benzodiazepines via a Tandem Condensation/[1,5]‐Hydride Transfer/Cyclization Process

“…Benzodiazepines (BDZs), particularly 1,4‐benzodiazepines, are present in many natural alkaloids and have long been the center of attention because of their diverse array of pharmacological activities (Figure ), which make them potential candidates for use in anti‐cancer, anti‐infective,, antihypertensive, anxiolytic, hypnotic, and anti‐HIV drugs. Furthermore, the application of benzodiazepines has been extended to the treatment of bipolar disorder– and chronic back pain .…”

“…Because of the significance of benzodiazepines, much effort has been devoted to accessing this class of compounds via, for example, the Ugi condensation, Friedel‐Crafts reaction, click chemistry,, carboamination, ring expansion reactions,, and aza‐Michael cyclization . While each of these methods affords a series of benzodiazepines and has great potential utility in the new drug discovery, preparative difficulties and complex operations have restricted their extensive application . Thus, the development of efficient methods for the construction of the benzodiazepine skeleton still remains a highly desirable yet challenging task.…”

A simple and one-pot synthesis of 2,3,4,5-tetrasubstituted 4,5-dihydro-3H-1,4-benzodiazepines

“…7 Another 1,4-benzodiazepines were obtained from Pd-catalyzed coupling of N-allyl-2-aminobenzylamine derivatives with aryl bromides, 8 or by the reaction of 2-aminobenzylamine with 1,2-diaza-1,3-dienes. 9 Although much effort has been directed toward the construction of 1,4-benzodiazepines, fewer methods for the synthesis of 4,5-dihydro-3H-1,4-benzodiazepines have been developed. To further discover molecules with potent and selective biological activity, it is of importance to explore new methodology for the synthesis of novel 4,5-dihydro-3H-1,4-benzodiazepine entities.…”