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.     

4,5-Dihydro-7,8-dimethoxy-1-phenyl-3H-2,3-benzodiazepin-4-one

The title compound, C₁₇H₁₆N₂O₃, is an antagonist for AMPA/kainate receptors. The mol­ecule has its seven-membered oxa­diazo­le ring in a boat conformation. Asymmetry of the two methoxy bond angles is evident, with (Me)O—C—C angles of 115.45 (12) and 124.78 (13)°, and 114.67 (12) and 125.31 (12)°. A centrosymmetric dimer involving the HN—CO moieties, with an N⃛O distance of 2.876 (2) Å, graph set R(8), is further linked into chains through methoxy Csp³—H⃛N hydrogen bonds, with a C⃛N distance of 3.418 (2) Å.     

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.     

Bromo derivatives of 4-phenyl-2,3-dihydro-1h-1,5-benzodiazepin-2-one

Monobromo and dibromo derivatives were synthesized by bromination of 4-phenyl-2,3-dihydro-1H-1,5-benzodiazepin-2-one with bromine under various conditions and with N-bromosuccinimide in CCl₄. 7-Bromo- and 8-bromo-4-phenyl-2,3-dihydro-1H-1,5-benzodiazepin-2-ones were obtained by condensation of 4-bromo-o-phenylenediamine with benzoylacetic ester in refluxing xylene. The UV and PMR spectra of the products are discussed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 411–415, March, 1978.     

Molecular-crystal structure of 5-methyl-1,2-dihydro-3H-1,4-benzodiazepin-2-one

5-Methyl-1,2-dihydro-3H-1,4-benzodiazepin-2-one, which is an antagonist of 5-aryl-1,2-dihydro-3H-1,4-benzodiazepin-2-ones, was subjected to a complete x-ray diffraction study. The crystals have monoclinic syngony witha = 11.456(5), b = 8.195(3), c = 9.257(4) Å, = 93.10(3) °, and space group P2₁/b. The nonplanar molecules (with a boat conformation) form cyclic dimers by means of NH...O hydrogen bonds (2.937 Å) in the vicinity of the center of symmetry (0, 0, 1/2). Replacement of the phenyl ring in the 5 position by a less bulky methyl group does not lead to appreciable changes in the geometry and conformation of the heteroring. It is assumed that the substituent in the 5 position plays a role in determining the character of the pharmacological action of 1,4-benzodiazepines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 985–988, July, 1982.     

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.     

Structure of 1-phenyl-1-thioxo-2,5-dimethyl-3-morpholinomethyl-phosphorinan-4-one

Chemical Sciences Institute, Kazakh Academy of Sciences. Institute for Heteroorganic Compounds, USSR Academy of Sciences. Translated from Zhurnal Strukturnoi Khimii, Vol. 31, No. 1, pp. 184–186, January–February, 1990.     

Synthesis and nitration of 4-phenyl-2,3-dihydro-1H-1,5-benzodiazepin-2-one

Analysis of the UV spectra of the reaction products shows that in the nitration of 4-phenyl-2,3-dihydro-1H-1,5-benzodiazepin-2-one the nitro group is directed to the benzodiazepine ring rather than to the phenyl ring to give a 7-nitro derivative.Translated from Khimiya Geterotsiklieheskikh Soedinenii, No. 4, pp. 525–528, April, 1977.     

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.     

Methylation of 5-Phenyl-1,4-benzodiazepin-2-one derivatives with N,N-dimethylformamide-dimethyl acetal

A novel method for N-methylation of the cyclic amide in the 1,4-benzodiazepine ring system is presented. Methods traditionally used involve treatment of the 1,4-benzodiazepinone anion with an alkyl halide. It has been demonstrated that these derivatives can be methylated on the amide nitrogen atom by use of dimethyl-formamide dimethyl acetal which acts as both reagent and solvent for the reaction.     

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.