An expedient synthesis of 3-amino-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one

Racemic 3-amino-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one, 2, was prepared in four steps utilizing a novel mercuric ion assisted ammonia displacement of an N-acyl alkylthioglycine amide 5.     

Synthesis and crystalline and molecular structure of hydrochloride of 1-[2(2,3-dihydro-1,3,4-oxadiazolyl-5-one)]methyl-7-bromo-5-prenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-one

By the interaction of 1-hydrazinocarbonylinethyl-7-bromo-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-one with phosgene, the compound 1-[2(2,3-dihydro-1, 3,4-oxadiazolyl-5-one)jmethyl-7-bromo-5-phenyl-1, 2-dihydro-3H-1, 4-benzodiazepin-2-one has been synthesized. Spectroscopic methods and x-ray structure analysis have been used to establish the crystalline and molecular structure of this new derivative of 1, 4-benzodiazepine.A. V. Bogatskii Physicochemical Institute, National Academy of Sciences of Ukraine, Odessa 270080. Institute of Applied Chemistry, Academy of Sciences of the Republic of Moldova, Kishinev 277028. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 689–693, May, 1995. Original article submitted March 17, 1995.     

Microbiological synthesis of 7-bromo-5-(o-chlorophenyl)-3-hydroxy-1,2-dihydro-3H-1,4-benzodiazepin-2-one by immobilized actinomycetes

It has been shown that the highest yields (15%) of 7-bromo-5-(o-chlorophenyl)-3-hydroxy-1,2-dihydro-3H-1,4-benzodiazepin-2-one are obtained by the use of the cells of actinomycetes immobilized in poly(vinyl alcohol) in the presence of the cosubstrate 7-bromo-5-(o-chlorophenyl)-3-methyl-1,2-dihydro-3H-1,4-benzodiazepin-2-one.     

Microbiological synthesis of 7-bromo-5-(o-chlorophenyl)-3-hydroxy-1,2-dihydro-3H-1,4-benzodiazepin-2-one by immobilized actinomycetes

It has been shown that the highest yields (15%) of 7-bromo-5-(o-chlorophenyl)-3-hydroxy-1,2-dihydro-3H-1,4-benzodiazepin-2-one are obtained by the use of the cells of actinomycetes immobilized in poly(vinyl alcohol) in the presence of the cosubstrate 7-bromo-5-(o-chlorophenyl)-3-methyl-1,2-dihydro-3H-1,4-benzodiazepin-2-one.Physicochemical Institute, Academy of Sciences of the Ukrainian SSR, Odessa. Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 779–783, November–December, 1981.     

7-Bromo-5-phenyl-1,2-dihydro-3H-1,3,5-benztriazepin-2-one

7-Bromo-5-phenyl-1,2-dihydro-3H-1,4-benztriazepin-2-one was obtained by thermolysis of the syn-4-phenylsemicarbazone of 2-aminobenzophenone. Its molecular and crystal structure were established by X-ray crystallography. The nature of the hydrogen bonds between molecules of the compound in solution and in the crystalline state was determined by IR spectroscopy and X-ray crystallography.     

Nitration products of substituted 1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-ones

Highly substituted, novel, 1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-ones were obtained by direct nitration of the corresponding mono- or di-substituted 5-phenyl-1,4-benzodiazepines. Substituent effects and the orientation of aromatic substituents in the nitration products are discussed. The single-crystal X-ray structural data for one of these products, 18 , is given.     

Mass spectra of 3-arylidene-1H-2,3-dihydro-1,4-benzodiazepin-2-ones

The scheme of the fragmentation of arylidene derivatives of 5-phenyl-1,4-benzodiazepin-2-ones was established by means of high-resolution mass spectrometry. One of the principal fragmentation pathways of these compounds is cleavage of the 2C-3C and 4N-5C bonds to give two fragments. Depending on the substituents in the arylidene portion of the molecule, the charge is localized primarily on one or the other of these fragments. The mechanism of the formation of the [ArCH₂]⁺ ions observed in the mass spectra of all of the investigated compounds was established on the basis of the mass spectrum of the 1N-deuterium-labeled compound. The specific fragmentation pathways due to the ortho effect of the nitro group are discussed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1690–1696, December, 1976.     

Synthesis and structure of 3-arylidene and 3-hetarylidene-1,2-dihydro-3H-1,4-benzodiazepin-2-ones and their affinity toward CNS benzodiazepine receptors

The condensation of 5-aryl-7-bromo-1,2-dihydro-3H-1,4-benzodiazepin-2-ones with aromatic aldehydes gives 5-aryl-3-arylidene-and 5-aryl-7-bromo-3-hetarylidene-1,2-dihydro-3H-1,4-benzodiazepin-2-ones. X-ray diffraction structural analysis yielded the molecular and crystal structures of 7-bromo-3-(4′-methoxybenzylidene)-5-phenyl-1,2-dihydro-3H-1,4-diazepin-2-one and showed that this compound has cis configuration. Radioligand analysis was used to study the affinity of these products toward central nervous system and peripheral benzodiazepine receptors. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1213–1225, August, 2007.     

Reactions of 7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2,2-dioxide in Various pH Solutions

Diazepam ( 1 ) is a frequently prescribed hypnotic/anxiolytic drug worldwide. 7-Chloro-1,3-dihydro-l-methyl-5-phenyl-2H-1,4-benzodiazepin-2,2-dioxide ( 2 ) is an initial alkaline hydrolysis product of 1. The mechanisms in the conversion of 2 to 2-methylamino-5-chloro-α-(phenylbenzylidene)glycinate ( 3 ), 2-methylamino-5-chlorobenzophenone ( 4 ), and 1 in aqueous solutions with pH ranging from 0 to 12.2 is the subject of this report. Results of temperature-dependent hydrolysis kinetics and product identification indicated that: (1) in solutions with pH between 7 and 12.2, 2 underwent a ring-opening reaction to form 3; the rate decreased with increasing pH. (2) In solutions with pH between 2 and 7, 2 was rapidly converted to 3, followed by a pH-dependent conversion to 4 ; the rate increased with decreasing pH and became less sentitive to pH at pH ≤ 4.5. (3) In solutions with pH between 0 and 2, 2 was rapidly converted to 4 and 1; the percentage of 1 increased with decreasing pH. (4) A 2 containing one oxygen-18 atom lost 50% of its oxygen-18 following conversion to 1 in 1 M HCl. In addition to understanding the mechanism in the transformations of 2 in various pH solutions, this study established a simple and efficient method in the quantitative conversion of 1 to 4 and in the preparation of an oxygen-18-containing 1 at C2 position.     

New synthesis of 7-bromo-1, 3-dihydro-3-hydroxy-5-(2′-pyridyl)-2H-1,4-benzodiazepin-2-one

A new synthesis of 7-bromo-1,3-dihydro-3-hydroxy-5-(2′-pyridyl)-2H-1,4-benzodiazepin-2-one ( 5 ) is described. Starting from bromazepam ( 3 ), C(3) acylation with lead tetraacetate/potassium iodide in acetic acid affords 4 , while its mild hydrolysis according to our recently described method (5) gives 5 . Improved hexamine cyclization of 1 into 3 , via quaternary hexaminium salt 2 , is discussed, and identification of the intermediates 7 and 8 is performed. Compound 5 undergoes on melting, or on brief heating in glacial acetic acid, the thermal rearrangement into quinazolin-2-aldehyde ( 13 ), the structure of which is confirmed by oxidation into the ester 14 , which in turn was hydrolyzed to the acid 15 . The same compound ( 5 ) rearranges on heating with manganese(III) acetate in acetic acid into the 3-amino-2-quinolone derivative 6 . On heating in glacial acetic acid in the presence of lead tetraacetate/potassium iodide (or iodine), compound 4 , in addition to giving the aldehyde 13 , ester 14 and acid 15 rearrangement products, affords 1,2-dihydroquinazolin-2-carboxylic acid 16 .     

Basic hydrolysis of 3-acetoxy-7-bromo-5-(o-chlorophenyl)-1-ethoxycarbonylmethyl-1,2-dihydro-3H-1,4-benzadiazepin-2-one

The selective basic hydrolysis of 3-acetoxy-7-bromo-5-(o-chlorophenyl)-1-ethoxycarbonylmethyl-1,2-dihydro-3H-1,4-benzdiazepin-2-one has been carried out, resulting in the sequential formation of 3-hydroxy-1-ethoxycarbonylmethyl-, 3-hydroxy-1-methoxycarbonylmethyl-, and 3-hydroxy-1-carboxymethyl derivatives. The structure of the 1-methoxycarbonylmethyl derivatives has been established by x-ray structural analysis.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 685–690, May, 1990.     

Chloro derivatives of 4-phenyl-2,3-dihydro-1H-1,5-benzodiazepin-2-one

The chlorination of 4-phenyl-2,3-dihydro-1H-1,5-benzodiazepin-2-one with N-chlorosuccinimide takes place at the methylene group to give mono and diehloro derivatives. In the reaction of the diazepinone with sulfuryl chloride chlorine is incorporated in the 1 or 3 position or in both the 1 and 3 positions, as well as in the para position of the phenyl substituent; in the presence of anhydrous aluminum chloride substitution takes place in the methylene group of the heteroring and in the 8 position of the annelated benzene ring.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 405–409, March, 1982.     

Vilsmeier reaction with 4-phenyl-2,3-dihydro-1H-1,5-benzodiazepin-2-one

4-Phenyl-2,3-dihydro-1H-1,5-benzodiazepin-2-one reacts with the Vilsmeier reagent to give a 3-dimethylaminomethylidene derivative, the hydrolysis of which leads to 3-formyl-4-phenyl-2,3-dihydro-1H-1,5-benzodiazepinone.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 223–225, February, 1984.