An Efficient Synthesis of N-Alkyl-1,4-Dihydro-4-Oxo-3-Quinolinecarboxylic Acid via 2-(2',2',2'-Tri-Chloro)Ethylidene-3-Oxo-3-(2'-Chlorophenyl)Propionate

A clay catalyzed synthesis of 2-(2',2',2'-trichloro)ethylidene-3-oxo-3-(2''-chlorophenyl)propionate (2) and its application for the preparation of various N-alkyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids (5a-e) has been described.     

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.     

Some derivatives of 3-aryl-2H-1,4-benzoxazine

Arylacyl esters of o-acetamidophenol, which are cyclized to 3-aryl-2H-1,4-benzoxazines by a saponification of the acetamido group, are obtained by the reaction of -bromomethyl aryl ketones with potassium o-acetamidophenoxide.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 164–166, February, 1971.     

Facile Synthesis of 2H-1,4-Benzothiazin-3(4H)-ketoximes and 2H-1,4-Benzoselenazin-3(4H)-ketoximes Promoted by SmI2

Abstract

2H-1,4-Benzothiazin-3(4H)-ketoximes and 2H-1,4-benzoselenazin-3(4H)-ketoximes were synthesized by the reductive cyclization of bis(o-nitrophenyl) disulfides or diselenides with aromatic or aliphatic β-nitroethylenes using SmI₂ in moderate to good yields under mild conditions.     

Hypervalent Iodine Oxidation of 2-Aryl-1,2,3,4-tetrahydro-4-quinolones: An Easy Access to 2-Aryl-4-quinolones

Oxidation of 2-aryl-1,2,3,4-tetrahydro-4-quinolones (1a-e) using iodobenzene diacetate in methanolic potassium hydroxide leads to dehydrogenation of 1 thereby providing an easy access to 2-aryl-4-quinolones (2a-e).     

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.     

Synthesis of some new 4,5-substituted-4H-1,2,4-triazole-3-thiol derivatives

In this study appropriate hydrazide compounds, furan-2-carboxylic acid hydrazide (1) and phenylacetic acid hydrazide (2) were converted into 1,4-substituted thiosemicarbazides 4a-e and 5a-e and 4-amino-5-(furan-2-yl or benzyl)-4H-1,2,4-triazole-3-thiols 7 and 10. The 1,4-substituted thiosemicarbazides were then converted into 5-(furan-2-yl or benzyl)-4-(aryl)-4H-1,2,4-triazole-3-thiols 8a-e and 9a-e. In addition, the azomethines 11a-d and 12a-d were prepared from the corresponding arylaldehydes and the 4-amino-5-(furan-2-yl or benzyl)-4H-1,2,4-triazole-3-thiols 7 and 10. The structures of all the synthesized compounds were confirmed by elemental analyses, IR, (1)H-NMR and(13) C-NMR spectra.     

Oxidative behaviour of 3-aryl-2H-1,4-benzoxazines

Autoxidation of 3 - phenyl - 2H - 1,4-benzoxazine 8 gives 2 - hydroxy -3 - phenyl - 2H - 1,4-benzoxazine 13, 3 - phenyl - 2H - 1,4-benzoxazin - 2 - one 11, and 2 - phenylbenzoxazole 10 according to the conditions. Oxidation of 8 with DDQ in the presence of air gave mainly the bisacetal 17 but in the absence of air the major product was trans-Δ^2,2′-bi-(3-phenyl-2H-1,4-benzoxazine) 21a. Corresponding dimers were obtained from the 3-p-bromophenylbenzoxazine 9. The trans-isomers 21a and 22a are photochromic and change into their cis-isomers on exposure in solution to direct sunlight.     

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.     

Efficient Synthesis of Novel 3-[5-(1H-Benzimidazol-2-Ylmethanesulfonyl)-4-Phenyl-4H-(1,2,4)Triazol-3-Yl]-1H-(1,8)Naphthyridin-4-One Derivatives

Abstract

of 1,4-dihydro-4-oxo-1,8-naphthyridine-3-carbohydrazide (4) with substituted phenyl isothiocyanates (5) in ethanol under reflux for 30 min gave thiosemicarbazide derivatives 6, which on cyclization in 2N NaOH under refluxing conditions for 1 h resulted in 3-(5-mercapto- 4-phenyl-4H-1,2,4-triazol-3-yl)-1,8-naphthyridin-4(1H)-one (7). Alternatively, 7 could also be prepared from following sequence of reactions, i.e., 4 → 8 → 7. In another sequence of reactions, condensation of 7 with chloroacetic acid in dimethylformamide (DMF) and K₂CO₃ as a mild base at 120 °C for 2 h resulted in 2-((5-(1,4-dihydro-4-oxo-1,8-naphthyridin-3-yl)-4-phenyl-4H-1,2,4-triazol-3-yl)sulfanyl)acetic acid (10). The latter, on reaction with substituted o-phenylenediamine (11) in 6N HCl for 4 h yielded 3-(5-((1H-benzo[d]imidazol-2-yl)methylthio)-4-phenyl-4H-1,2,4-triazol-3-yl)-1,8-naphthyridin-4(1H)-one (12). Alternatively, 12 could also be prepared by reacting 7 with 13 in DMF and K₂CO₃ as a mild base at 120 °C for 2 h, followed by oxidation with H₂O₂ resulting in the corresponding sulfonyl derivatives 14.     

Synthesis of 2-acetyl-3-methyl-4H-1,4-benzothiazine and its derivatives

Summary 2-Aminothiophenol (1) reacts with 3-chloro-2,4-pentanedione (2) in the presence of pyridine to form 2-acetyl-3-methyl-4H-1,4-benzothiazine (3) in high yields. Reaction of3 with hydrazine gives 4-(2-aminophenylthio)-3,5-dimethylpyrazole (5). Condensation of3 with 4-nitrobenzaldehyde yields the corresponding Schiff base7. Hydroxylamine with benzothiazine3 affords 3,9a-dimethyl-3a, 9a-dihydro-9H-isoxazolo[4,5-b][1,4]benzothiazine (8).

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Synthese von 2-Acetyl-3-methyl-4H-1, 4-benzothiazin und seinen Derivaten

Zusammenfassung 2-Aminothiophenol (1) reagiert mit 3-Chlor-2,4-pentandion (2) in Anwesenheit von Pyridin unter Bildung von 2-Acetyl-3-methyl-4H-1,4-benzothiazin (3) in sehr hoher Ausbeute. Benzothiazin3 kondensiert mit Hydrazin zu 4-(2-Aminophenylthio)-3,5-dimethylpyrazol (5), dessen Aminogruppe reagiert mit 4-Nitrobenzaldehyd zu einer Schiffschen Base (7), die spektroskopisch charakterisiert wurde. Benzothiazin3 mit Hydroxylamin ergibt 3,9a-Dimethyl-3a,9a-dihydro-9H-isoxazolo[4,5-b][1,4]benzothiazin (8). Die Stereochemie der letztgenannten Verbindung wurde ermittelt.

     

Synthesis of 4-acyl-2,3-dihydro-4H-1,4-oxazines

The synthesis of 4-acyl-2,3-dihydro-4H-1,4-oxazines ( 6a-h ) via acid dehydration of 4-acyl 2- and 3-morpholinols is described. During dehydration of 2-morpholinols 3d,e , N-alkylisoquinolones 7a-e were also isolated.     

Synthesis of Fluorine-Containing 2-(1-Aryl-4-oxo-1,4-dihydrocinnolin-3-yl)-2-oxoacetic Acids

Acid hydrolysis of ethyl 2-(1-aryl-5,6,7,8-tetrafluoro-4-oxo-1,4-dihydrocinnolin-3-yl)-2-oxoacetates gives 2-(1-aryl-5,6,7,8-tetrafluoro-4-oxo-1,4-dihydrocinnolin-3-yl)-2,2-dihydroxyacetic acids which undergo dehydration on heating in toluene to afford 2-(1-aryl-5,6,7,8-tetrafluoro-4-oxo-1,4-dihydrocinnolin-3-yl)-2-oxoacetic acids. Reactions of the latter with excess morpholine result in replacement of two fluorine atoms in positions 5 and 7 by the amine residues.     

Studies on the chemistry of 1,4-oxazines,XV: Synthesis of ethyl 3,4-dihydro-4-tosyl-2H-1,4-benzoxazine-3-carboxylate

A four step synthesis of ethyl 3,4-dihydro-4-tosyl-2H-1,4-benzoxazine-3-carboxylate (4) from the acetal5 is described.

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Studien zur Chemie der 1,4-Oxazine, 15. Mitt.: Synthese des 3,4-Dihydro-4-tosyl-2H-1,4-benzoxazin-3-carbonsäureethylesters (Kurze Mitteilung)

Zusammenfassung Eine Synthese des 3,4-Dihydro-4-tosyl-2H-1,4-benzoxazin-3-carbon-säureethylesters (4) über vier Stufen wird, ausgehend vom Acetal5, beschrieben.

     

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.     

Bioglycerol-Based Sulfonic Acid-Functionalized Carbon Catalyst as an Efficient and Reusable Catalyst for One-Pot Synthesis of 3- Substituted-2H-1,4-Benzothiazines

Abstract

A simple and efficient synthetic protocol has been developed for the synthesis of 3-substituted-2H-1,4-benzothiazines by using bioglycerol-based sulfonic acid-functionalized carbon catalyst, devoid of corrosive acidic and basic reagents. The developed method has the advantages of good to excellent yields, short reaction times, operational simplicity, and a recyclable catalyst.     

Synthesis and some conversions of 4-aryl-6-methyl-2-methoxy(phenyl)-5-nitro-1,4-dihydropyrimidines

The reaction of 1-arylidene-1-nitropropan-2-ones with O-methylisourea (or benzamidine) in the presence of aluminum oxide gave 4-aryl-6-methyl-2-methoxy(phenyl)-5-nitro-1,4-dihydropyrimidines. It was shown that the reactions of the compounds synthesized with electrophilic agents proceed at the exocyclic methyl group, as well as at the N₍₁₎, N₍₃₎, and C₍₅₎ atoms of the 1,4-dihydropyrimidine fragment of the molecule.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1398–1404, October, 1993.     

A PTC ASSISTED THIONATION: SYNTHESIS OF 2H-1,4- BENZOXAZINE-3(4H)-THIONES & 2h-1,4-BENZOTHIAZINE- 3(4H)-THIONES

A facile method for the conversion of 2H-1,4-benzoxa/thiazine-3(4H)-ones to their respective thiones under PTC (P₂S₅/K₂CO₃/TEBA) conditions is reported.     

Reaction of 1-Aryl-1H-1,2,3-Triazole-4-Carbonyl Chlorides/Isothiocyanates with 3-Amino-5-Methylisoxazole

Abstract

1-Aryl-1H-1,2,3-triazole-4-carbonyl chlorides were selected as starting materials for the Boulton–Katritzky rearrangement. When 3-amino-5-methylisoxazole was acylated by 1-aryl-1H-1,2,3-triazole-4-carbonyl chlorides, 1-aryl-5-methyl-N-(5-methylisoxazol-3-yl)-1H-1,2,3-triazole-4-carboxamides 5 were obtained and no further rearrangement occurred. On the other hand, when 1-aryl-1H-1,2,3-triazole-4-carbonyl chlorides were first converted into isothiocyanates by the reaction with KSCN and then were allowed to react with 3-amino-5-methylisoxazole 4 in one pot, intermediate thioureas were formed and spontaneously transformed in statu nascendi into 1,2,4-thiadiazole derivatives 6.

GRAPHICAL ABSTRACT