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.     

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.     

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.     

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.     

液质联用同时测定大鼠尿液中6种苯二氮卓类药物

建立高效液相色谱串联质谱法同时测定大鼠尿液中的6种苯二氮卓类药物(BZDs).以乙酸乙酯为萃取溶剂,经液-液萃取前处理后检测.以地西泮为内标,流动相为甲醇-0.01％甲酸+5 mmol/L甲酸铵,梯度洗脱,柱温为40℃;流速为0.3 mL/min;进样量为2 μL,质谱采用电喷雾离子源正离子模式(ESI+).8-溴-1...     

Peculiarities of inclusion complex formation in the 1,4-benzodiazepine-benzene system

5-Phenyl-1-methyl-7-bromo-3-hydroxy-1,2-dihydro-3H-1,4-benzodiazepin-2-one and its 5-(o-chloro)-phenyl analog form 2:1 (host:guest) inclusion compounds with benzene. The crystal structures of the compounds were studied by the single-crystal XRD method and were interpreted as host (H) (benzodiazepine) — guest (G) (benzene solvent molecule) complexes. The studied structures, revealing H-H and H-G interactions as both typical hydrogen bonds and π-π, C-H?π weak interactions, may serve as models for ligand-receptor binding.     

A novel conversion of acetylenic 1,2,4-triazoles into 3-alkyl-5-arylpyridazines

Bromination of 2-aryl-1-[1,2,4]triazol-1-ylalk-3-yn-2-ols gives 6-bromo-7-hydroxy-5-alkyl-7-aryl-7,8-dihydro-[1,2,4]triazolo[1,2-a]pyridazin-4-ylium salts, which are converted by treatment with strong alkali into novel 3-alkyl-5-arylpyridazines.     

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 .     

Palladium-catalyzed heteroannulation leading to heterocyclic structures with two heteroatoms: a highly regio- and stereoselective synthesis of (Z)-4-alkyl-2-alkyl(aryl)idene-3,4-dihydro-2H-1,4-benzoxazines and (Z)-3-alkyl(aryl)idene-4-tosyl-3,4-dihydro-2H-1,4-benzoxazines.

A highly convenient method has been developed for the synthesis of (Z)-4-alkyl-2-alkyl(aryl)idene-3,4-dihydro-2H-1,4-benzoxazines 9 and (Z)-3-alkyl(aryl)idene-4-tosyl-3,4-dihydro-2H-1,4-benzoxazines 34-38 through palladium-copper-catalyzed reactions. Aryl halides 7 reacted with 2-[N-alkyl(benzyl)-N-prop-2'-ynyl]aminophenyl tosylate 6 in the presence of (PPh3)2PdCl2 (3 mol %), CuI(5 mol %) in triethylamine at room temperature to yield 2-[N-alkyl(benzyl)-N-(3-aryl-prop-2'-ynyl)]-aminophenyl tosylates 8 in extremely good yields (72-96%). The latter could then be cyclized with KOH in ethanol-water to Z-9 in a highly regio- and stereoselective manner. Similarly, palladium-copper-catalyzed reaction of 2-(prop-2'-ynyloxy)aniline (21) with aryl iodides 7 led to 22-26 which after tosylation and cyclization with cuprous iodide in CH3CN in the presence of K2CO3 and Bu4-NBr led to the (Z)-3-alkyl(aryl)idene-4-tosyl 3,4-dihydro-2H-1,4-benzoxazines 34-38 in good overall yields. The Z-stereochemistry of the products was established from 1H NMR spectra, 3JCH values (between vinylic proton and methylenic carbon of the heterocyclic ring), NOE experiments, and X-ray analysis. The method was also found to be suitable for the synthesis of bis(benzoxazinylated) derivatives 17, 39, and 2-alkyl-3,4-dihydro-2H-1,4-benzoxazines 18. Our method for the synthesis of 3,4-dihydro-2H-1,4-benzoxazines is highly efficacious, using easily available starting materials under very mild conditions. Also the synthesis of some novel 5-substituted uracil derivatives 40 and 41 containing the benzoxazinyl moiety and of potential biological interest is being reported.     

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.     

1,4-Benzodiazepines and their derivatives

A series of compounds of the merocyanine dye type was obtained by the reaction of 1-acetyl-1,3-dihydro-2H-1,4-benzodiazepin-2-ones and 1,3-dihydro-2H-1,4-benzodiazepine-2-thiones with 2-methylmercapto-3-ethylbenzothiazolium tosylate, 2-methylmercapto-3,4,5-trimethylthiazolium bromide, 2-methylmercapto-3-methyl-5-phenyloxazolium methosulfate, and 1,3,3-trimethyl-2-formylmethyleneindoline. The hydrogen atoms of the methylene group of the 1-unsubstituted and 1-alkyl-substituted 1,3-dihydro-2H-1,4-benzodiazepin-2-ones are of low mobility, and the indicated compounds do not undergo condensation reactions with electrophilic agents.See [6] for communication VI.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 992–994, July, 1971.     

An anomalous reaction of 7-chloro-2-hydrazono-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepine with sodium acetate and 1,1′-carbonyldiimidazole

The addition of 7-chloro-2-hydrazono-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepine 3 to a mixture of sodium acetate and 1,1′-carbonyldiimidazole 1 at room temperature gave, in moderate yields, carbonyl-1,1′-bis[7-chloro-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-ylidene hydrazone] 7 instead of the expected 2-acetylhydrazono-7-chloro-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepine 4 .     

1,4-benzodiazepines and their cyclic homdlogs and analogs

The transformations (acylation, condensation with aldehydes, and diazotization) of 7- and 3-amino-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-ones are examined. It is shown that the action of P₂S₅ on 3-acetamidobenzodiazepinone leads to replacement of the oxygen atom of the acetyl group by a sulfur atom. The polarographic reduction of 7-arylideneamino-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-ones was studied.See [8] for communication 29.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No, 4, pp. 545–549, April, 1979.     

1,2,4-Triazines – products of reaction of thiocarbohydrazide and its alkyl(aryl)-substituted derivatives with 1,2-dicarbonyl compounds

The reaction of a series of 1,2-dicarbonyl compounds with thiocarbohydrazide and its 1- and 1,4-alkyl-(aryl)-substituted analogs has been studied. Treatment of diacetyl with the polynucleophiles indicated gives monohydrazones and/or 5-methylene-4,5-dihydro-2H-[1,2,4]triazine-3-thiones. Reaction of phenylglyoxal and benzil with thiocarbohydrazide yields 5-hydroxy- or 5-alkoxy-4,5-dihydro-2H-[1,2,4]triazine-3-thiones depending on the nature of the solvent. The products of condensation with 1,1-dimethylthiocarbohydrazide showed a thiocarbonohydrazone – 5-hydroxy-4,5-dihydro-2H-[1,2,4]tri-azine-3-thione ring-chain type equilibrium.     

Rearrangement of 1,4-benzodiazepin-2,4-diones to 3,l-benzoxazin-4-ones

Treatment of 7-chloro-3,4-dihydro-1H-1,4-benzodiazepin-2,5-dione (Ia) with refluxing acetic anhydride in the presence of pyridine afforded 6-chloro-2-methyl-4H-3,1-benzoxazin-4-one (IIa). A plausible reaction path for this novel rearrangement reaction is described: Ia → 4-acetyl-7-chloro-3,4-dihydro-lH-1,4-benzodiazepin-2,5-dione → 7-chloro-1,4-diacetyl-3,4-dihydro-lH-1,4-benzodiazepin-2,4-dione → IIa. When 7-chloro-3,4-dihydro-4-methyl-lH-1,4-benzodiazepin-2,5-dione (Ib), 3,4-dihydro-4-methyl-1H-1,4-benzodiazepin-2,5-dione (Id) and 3,4-dihydro-1-methyl-1H-1,4-benzodiazepin-2,5-dione (Ie) were allowed to react with acetic anhydride under conditions similar to those used for the rearrangement reaction, only acetylation occurred.     

Convenient synthesis of some optically active 1,4-benzodiazepin-2,5-diones

Isatoic anhydride was reacted with several L-amino acids to give the corresponding （2S）-N-（o-aminobenzoyl）-2-alkylaminoacetic acids. The latter compounds were treated with phosphoryl chloride under reflux temperature to afford the cyclized products, （3S）-3-alkyl-3,4-dihydro- 1 H- 1,4-benzodiazepin-2,5-diones. 2007 M. Bakavoli. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.     

Preparation and biological properties of inclusion compounds of calix[4]arene and 1,4-benzodiazepinone derivatives

The possibility of enhancing the oral bioavailability of certain 1,4-benzodiazepinones by using them as complexes with a series of calix[4]arene derivatives was examined. All the inclusion compounds prepared exhibit anticonvulsant activity by antagonism with Corazol spasmodic agent. Complexes with 25,27-bis[(hydrazinocarbonyl)methoxy]-26,28-dihydroxy-p-tert-butylcalix[4]arene exhibit higher pharmacological activity compared to the starting 7-bromo-5-(o-chloro)phenyl-and 1-hydrazinocarbonylmethyl-7-bromo-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-ones.     

Molecular and crystal structure of 1,2-dihydro-3H-1,3,4-benzotriazepines

Three novel 1,2-dihydro-3H-1,3,4-benzotriazepines have been synthesized: 7-bromo-5-phenyl-3-phenylcarbamoyl-1,2-dihydro-3H-1,3,4-benzotriazepin-2-one, 7-bromo-5-phenyl-1,2-dihydro-3H-1,3,4-benzotriazepin-2-thione, and 7-methyl-5-phenyl-1,2-dihydro-3H-1,3,4-benzotriazepin-2-one. Their crystal structures have been determined using X-ray analysis. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1048–1056, July, 2006.     

A new course of the Perkin cyclization of 2-(2-formyl-6-methoxyphenoxy)alkanoic acids. Synthesis of 2-alkyl-7-methoxy-5-nitrobenzo[b]furans

2-Alkyl-7-methoxy-5-nitrobenzo[b]furan, 2-alkyl-9-methoxy-7-nitro-3-oxo-2,3-dihydro-5H-benzo[e][1,4]-dioxepin-5-yl acetate and 2-alkyl-5-hydroxy-9-methoxy-7-nitro-5H-benzo[e][1,4]-dioxepin-3-one were formed as a result of the cyclization of 2-(2-formyl-6-methoxy-4-nitrophenoxy)alkanoic acids under classical Perkin reaction conditions. The products were characterized by spectroscopic methods and the mechanism of the cyclization is discussed.