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.     

Special features of the alkylation of 7-bromo-5-(2-chlorophenyl)- 3-hydroxy-1,2-dihydro-3h-1,4-benzo- diazepin-2-one with alkyl tosylates

On interacting 7-bromo-5-(2-chlorophenyl)-3-hydroxy-1,2-dihydro-3H-1,4-benzodiazepin-2-one with methyl, hexyl, dodecyl, and cetyl tosylates, 1-alkyl-7-bromo-5-(2-chlorophenyl)-1,2,4,5-tetrahydro-3H-1,4-benzodiazepin-2,3-diones, and 1-alkyl-7-bromo-5-(2-chlorophenyl)-3-hydroxy-1,2-dihydro-3H-1,4-benzodiazepin- 2-ones were obtained. Only the dione was formed in the case of hexyl tosylate. On alkylating with methyl tosylate only the 3-hydroxy derivative was formed. It was shown that at pH 14 the 1-cetyl and 1-dodecyl-3-hydroxy derivatives were completely converted into the corresponding diones. The molecular and crystal structures of the compounds were established by X-ray structural analysis.     

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.     

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.     

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.     

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...     

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.     

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.     

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.     

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.     

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.     

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.     

A NOVEL SERIES OF PALLADIUM(II) AND PLATINUM(II) COMPLEXES WITH 1,4-BENZODIAZEPINES AS LIGANDS

Abstract

The complexing behaviour towards palladium(II) and platinum(II) halides of some 1,4-benzodiazepines is reported. The ligands used in this study are 7-chloro-2-methylamino-5-phenyl-3H-1,4-benzodiazepin-4-oxide, 1,3-dihydro-7-nitro-5-phenyl-2H-1,4-benzodiazepin-2-one and 7-chloro-1-methyl-5-phenyl-3H-1,4-benzodiazepin-2-one. The complexes have been studied by means of magnetic susceptibility measurements, infrared and far infrared spectra, electronic spectra and conductivity measurements. The most convincing structural evidence for these complexes is a square planar stereochemistry with bridging ligands joining two metal ions and terminal halides in the 1:1 complexes and terminal ligands and terminal halides in the 1:2 derivatives. Assignments for the metal-ligand and metal-halide bands have also been made.     

Nucleophilic Substitution in 1,5-Benzodiazepin-2-ones

The reaction of 3-bromo-4-phenyl-2,3-dihydro-1H-1,5-benzodiazepin-2-one with cyclic amines gives 3-aminoalkyl-4-phenyl-2,3-dihydro-1H-1,5-benzodiazepin-2-one. Thiazolo[4,5-b][1,5]benzodiazepine was isolated along with the substitution product when thiourea was used.     

Quinazolines and 1,4-benzodiazepines. XLVI. Photochemistry of nitrones and oxaziridines

The cyclic nitrones 7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one 4-oxide ( 5a ) and 1,3-dihydro-7-methylthio-5-phenyl-2H-1,4-benzodiazepin-2-one 4-oxide ( 5b ) are photoisomerized to readily isolable oxaziridines, 7-chloro-4,5-epoxy-5-phenyl-1,3,4–5-tetrahydro-2H-1,4-benzodiazepin-2-one ( 6a ) and 4,5-epoxy-5-phenyl-1,3,4,5-tetrahydro-7-methylthio-2H-1,4-benzo-diazepin-2-one ( 6b ). Oxaziridine 6b upon further irradiation gave ring expansion and ring contraction products, 4,6-dihydro-2-phenyl-9-methylthio-5H-1,3,6-benzoxadiazocin-5-one ( 7b ) and 4-benzoyl-3,4-dihydro-6-methylthioquinoxalin-2(1H)-one ( 8b ) respectively. The ring contraction product, 4-benzoyl-6-chloro-3,4-dihydroquinoxalin-2(1H)-one ( 8a ), was obtained from irradiation of oxaziridine 6a .     

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 .     

Synthesis of 3,7—Disubstituted 1,4—Benzodiazepin—2—one

A series of 3-methoxycarbonylpropoxy-7-(imidazol-4-ylpropinamide)-1,3-dihydrogen-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-ones,as farnesyltransferase(Ftase) inhibitors,were synthesized. The preparation of the key intermediate,7-amino-3-methoxycabonylpropoxy-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one,was improved.     

2-Quinazolinones and their cyclic homologs (review)

Methods for the synthesis of 2-quinazolinones, 1,2-dihydro-3H-1,4-benzodiazepin-2-ones, 1,2,3,4-tetrahydro-1,5-benzodiazocin-2-ones, and 1,2,3,4-tetrahydro-5H-1,6-benzodiazonin-2-ones are examined along with the peculiarities of their structure, their tautomerism, their chemical properties, and their biological activity.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 723–738, June, 1979.     

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 .     

Reaction of o-phenylenediamine with acetoacetic and α-chloroacetoacetic esters

The reactivities of acetoacetic and -chloroacetoacetic esters in the reaction with o-phenylenediamine are compared. In contrast to the available data, it was established that in polyphosphoric aicd (PPA) acetoacetic ester is converted to 4-methyl-2,3-dihydro-1H-1,5-benzodiazepin-2-one and ethyl 3-(2-aminoanilino)-crotonate, while chloroacetoacetic ester is converted to 2-methylbenzimidazole. At 20 °C chloroacetoacetic ester is converted to ethyl 2-chloro-3-(2-aminoanilino)crotonate. The conversion of this ester to 2-methyl-3-ethoxy-2,3-dihydro-1H-1,5-benzodiazepin-2-one was studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1255–1259, September, 1981.