Synthesis of 4-Pyridyl-2,3-dihydro-1H-1,5-benzodiazepin-2-ones

4-Pyridyl-2,3-dihydro-1H-1,5-benzodiazepin-2-ones were obtained by the condensation of ethyl nicotinoyl- or isonicotinoylacetates with o-phenylenediamine. Alkylation of the pyridylbenzodiazepinones with ethyl iodide under phase-transfer catalysis conditions occurred at the amide nitrogen of the heterocycle, whereas in nitromethane it occurred at the nitrogen of the pyridine substituent. Bromination with N-bromosuccinimide occurred at position 3 of the heterocycle. Pyridyldibenzodiazepinones underwent thermal rearrangement to derivatives of vinylbenzimidazole.     

Michael Additions on 2H-1,4-Benzothiazin-3-ones

Michael addition on 2H-1,4-benzothiazin-3-ones is studied in this communication. An approach towards the regioselective synthesis of Michael adducts is shown.     

Synthesis of 2-Benzylidene and 2-Hetarylmethyl Derivatives of 2H-1,4-Benzoxazin-3-(4H)-ones as Neuroprotecting Agents

A wide variety of the title compounds were synthesized by conventional and microwave methods in which the main step is a condensation of an aldehyde with a 1,4-benzoxazin-3-(4H)-one. In all cases, the Z diasteromers were the major products. Of particular importance is the synthesis of novel 2-(3,5-dibromo-4-hydroxy) and 2-(4-acetoxy-3,5-dibromobenzylidene derivatives of 2H-1,4-benzoxazin-3-(4H)-ones, four of which were shown in a previous publication to exhibit potent neuroprotecting properties. The yields of titled compounds ranged from 25 to 83%.     

Synthesis and structure of 1-substituted 1-Oxo-1,2-dihydro-4H-3,1-benzoxaphosphorins

1-X-1-Oxo-1,2-dihydro-4H-3,1-benzoxaphosphorins (X = CH₂Cl, Ph, and OH) were obtained by reacting ortho-(butoxymethoxymethyl)phenylmagnesium bromide with derivatives of chloromethylphosphonic and chloromethylphosphinic acids, followed by intramolecular alkylation. X-Ray diffraction was used to study the molecular and crystalline structure of one of these compounds (with X = OH).Institute of Physiologically Active Substances, Russian Academy of Sciences, 142432 Chernogolovka. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 9, pp. 2174–2180, September, 1992.     

A Short and Efficient Synthesis of Novel N-(2,3-dihydro-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl)-2-carboxamides

Summary.  Several novel N-(2,3-dihydro-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl)-2-carboxamides were prepared by acyl coupling of 2-aminobenzophenones with α-(benzotriazol-1-yl)-N-acylglycines followed by displacement of the benzotriazole ring with ammonia and cyclization of the resulting monoacyl aminals. In addition to high yields and shorter reaction sequences due to avoiding deprotection and acylation of the protected 3-amino-1,4-benzodiazepin-2-one intermediates, the present approach did not involve the use of toxic and odoriferous materials as is the case with other methods. Received September 20, 2000. Accepted (revised) November 29, 2000     

Ab initio molecular orbital study of energies and conformers of 3,4-dihydro-1,2-dithiin, 3,6-dihydro-1,2-dithiin, 4H-1,3-dithiin,and 2,3-dihydro-1,4-dithiin

Optimized geometries and energies for 3,4-dihydro-1,2-dithiin ( 1 ), 3,6-dihydro-1,2-dithiin ( 2 ), 4H-1,3-dithiin ( 3 ), and 2,3-dihydro-1,4-dithiin ( 4 ) were calculated using ab initio 6-31G* and MP2/6-31G*//6-31G* methods. At the MP2/6-31G*//6-31G* level, the half-chair conformer of 4 is more stable than those of 1 , 2 , and 3 by 2.5, 3.5, and 3.6 kcal/mol, respectively. The half-chair conformers of 1 , 2 , 3 , and 4 are 2.9, 7.1, 2.0, and 5.6 kcal/mol, respectively, more stable than their boat conformers. The calculated half-chair structures of 1 – 4 are compared with the calculated chair conformer of cyclohexane and the half-chair structures for cyclohexene, 3,4-dihydro-1,2-dioxin ( 5 ), 3,6-dihydro-1,2-dioxin ( 6 ), 4H-1,3-dioxin ( 7 ), and 2,3-dihydro-1,4-dioxin ( 8 ). © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 1064–1071, 1998     

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.     

Synthesis of 5-mercapto-1,2-dithiole-3-thiones and their transformation into 5-chloro-1,2-dithiol-3-ones

A number of 4-dialkylamino-5-mercapto-1,2-dithiole-3-thiones were synthesized by reactions of alkyl(diisopropyl)amines with S₂Cl₂. Their reactions with S₂Cl₂—DABCO unexpectedly gave 5-chloro-4-dialkylamino-1,2-dithiol-3-ones. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 143–147, January, 2006.     

Synthesis and Properties of 1,3-Diaryl-5,6-dihydro-8H-imidazo[2,1-c]-1,4-oxazinium Bromides

It has been established that the condensation of 3-(4-methoxyphenylamino)-5,6-dihydro-2H-1,4-oxazine with substituted phenacyl bromides occurs at the exocyclic nitrogen atom with formation of 3-aryl-3-hydroxy-1-(4-methoxyphenyl)-2,5,6,8-tetrahydro-3H-imidazo[2,1-c]-1,4-oxazinium bromides. By treatment of the latter with acetic anhydride 3-aryl-1-(4-methoxyphenyl)-5,6-dihydro-8H-imidazo[2,1-c]-1,4-oxazinium bromides are formed. The structures of the compounds synthesized were determined via ¹H NMR spectroscopy and X-ray diffraction.     

Selective synthesis of bis[1,2]dithiolo[1,4]thiazines from 4-isopropylamino-5-chloro-1,2-dithiole-3-ones

Reaction of 4-isopropylamino-5-chloro-1,2-dithiole-3-ones 3 and S₂Cl₂ in acetonitrile gave selectively 3-oxo-bis[1,2]dithiolo[1,4]thiazine-5-thiones 1 by the addition of triethylamine and bis[1,2]dithiolo[1,4]thiazine-3,5-diones 5 under the action of formic acid. 3,5-Diones 5 were also obtained by intramolecular cyclization of N,N-bis(5-chloro-3-oxo[1,2]dithiol-4-yl)amines 6 with S₂Cl₂ in the presence of Et₃N.     

Interaction of 3-p-toluoyl-1,2-dihydro-4H-pyrrolo-[2,1-c][1,4]benzoxazine-1,2,4-trione with benzylamine. Synthesis and crystal and molecular structure ofZ-3-(1-benzyl-2-hydroxy-4,5-dioxo-2-p-tolyltetrahydropyrrol-3-idene)-3,4-dihydro-2H-1,4-benzoxazin-2-one

3-p-Toluoyl-1,2-dihydro-4H-pyrrolo-[2,1-c][1,4]benzoxazine-1,2,4-trione reacts with benzylamine to yieldZ-3-(1-benzyl-2-hydroxy-4,5-dioxo-2-p-tolyltetrahydropyrrol-3-idene)-3,4-dihydro-2H-1,4-benzoxazin-2-one. The crystal and molecular structure of the latter compound was studied by X-ray structural analysis. Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 3, pp. 566–569, March, 1997.     

Synthesis of 4-Amino-6-R-4,5-dihydro-3-phenacylthio-1,2,4-triazin-5-ones and 8H-3-R-7-Aryl-1,2,4-triazino[3,4-b][1,3,4]thiadiazin-4-ones

A study was carried out on the reaction of 4-amino-6-R-2,3,4,5-tetrahydro-3-thioxo-1,2,4-triazin-5-ones with halo ketones in alkaline media to yield 4-amino-6-R-4,5-dihydro-3-phenacylthio-1,2,4-triazin-5-ones, which then convert to 8H-3-R-7-aryl-1,2,4-triazino[3,4-b][1,3,4]thiadiazin-4-ones.     

Synthesis of 5-Formyl and 5-Acyl-1,2-dithiole-3-ones

The preparation of new 5-formyl-, 5-acetyl- and 5-propionyl-1,2-dithiole-3-ones by oxidation of the corresponding 1,2-dithiole-3-thiones with mercuric acetate is described.     

A Simple Indirect Route for the Synthesis of N-Alkyl-4-imino-1,4-dihydro-2H-3,1-benzoxazin-2-ones

Summary. Novel N-alkyl-4-imino-1,4-dihydro-2H-3,1-benzoxazin-2-ones were synthesized in a single step by Baeyer–Villiger oxidation of N-alkyl-3-imino-2-indolinone derivatives in high yields. The structures of the products were determined by spectral data and by X-ray diffraction. Besides their novel structures, these compounds may have important biological activities and industrial applications.     

Reactions of 2H-3,4-dihydro-1,4-benzoxazin-6(8aH)-ones with 2,4,6-trimethylbenzonitrile oxide,III

Summary Regio-, stereo- and siteselectivity of the cycloadditions of trimethylbenzonitrile oxide with 2H-3,4-Dihydro-1,4-benzoxazin-6(8aH)-ones have been investigated. The structures of the obtained products were elucidated by means of homonuclear NOE difference spectroscopy and HMQC and HMBC spectra. The structure of 6-Benzyl-9a-methoxy-3-mesityl-9b-methyl-7,8,9a,9b-tetrahydro-3aH-1,2-oxazolo-[4,5-h]1,4-benzoxazin-4(6H)-on5 was elucidated from a single crystal X-ray structure analysis at ambient temperature: C₂₇H₃₀N₂O₄, M=446.55g/mol, monoclinic, P2₁/c,a=10.372 (34) Å,b=11.908 (21) Å,c=20.040 (34) Å, =97.16 (17)°,V=2455.8 (1.9)ų,Z=4,d _c=1.208g/cm³, =0.08mm^–1,R=0.0546.Dedicated to Prof. Ott with best wishes for his 70^th birthday     

Synthesis and Crystal Structure of 5-Amino-7-benzylseleno-8-cyano-3-ethoxycarbonyl-4-(2-furyl)-1,2-dimethyl-1,4-dihydro-1,6-naphthyridine

5-Amino-7-benzylseleno-8-cyano-3-ethoxycarbonyl-4-(2-furyl)-1,2-dimethyl-1,4-dihydro-1,6-naphthyridine was obtained by N-alkylation. X-ray crystallography showed the presence of two symmetrically conformers in the crystal.     

Synthesis of 4-Arylhydrazono-3-arylthiomethyl-4,5-dihydro-1H-1-R-5-pyrazolones

It has been established that interacting ethyl 2-arylhydrazono-4-arylthio-3-oxobutyrates with hydrazine, methylhydrazine, and phenylhydrazine forms 4-arylhydrazono-3-arylthiomethyl-4,5-dihydro-1H-1-R-pyrazolones.