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 substituted 4H-thiazolo[4,5-b][1]benzothiopyran-4-ones as possible schistosomicidal agents

Summary Interaction of ethyl 2-acetamido-5-bromothiazole-4-carboxylate (2) with 2-methyl-5-chlorothiophenol (3) afforded the thioether4, which was hydrolysed to the corresponding carboxylic acid5. Attempted cyclization of5 to6 yielded the decarboxylated product7. On the other hand, interaction of 2-acetamido-5-bromothiazole (9) with thiosalicylic acid (10) yielded the thioether11, which was cyclized to compound12. Acid hydrolysis of12 yielded the amino derivative13, which was reacted with certain selected alkyl halides using sodium hydride to afford compounds14–18.

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Synthese von substituierten 4H-Thiazolo[4,5-b][1]benzothiopyran-4-onen als mögliche schistosomicide Wirkstoffe

Zusammenfassung Die Reaktion von Ethyl 2-Acetamido-5-bromthiazol-4-carboxylat (2) mit 2-Methyl-5-chlorthiophenol (3) ergab den Thioether4, der zur entsprechenden Carbonsäure5 hydrolysiert wurde. Die versuchte Cyclisierung von5 zu6 ergab das Decarboxylierungsprodukt7. Andererseits ergab die Reaktion von 2-Acetamido-5-bromthiazol (9) mit Thiosalizylsäure (10) den Thioether11, der zu Verbindung12 cyclisiert werden konnte. Saure Hydrolyse von12 ergab das Aminoderivat13, das mit geeigneten Alkylhalogeniden unter Verwendung von Natriumhydrid zu den Verbindungen14–18 führte.

     

Synthesis of 2-Aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-ones and 7-Aryl-2,3,6,7-tetrahydro-5H-imidazo[2,1-b]-1,3-thiazin-5-ones

The reaction of 2-mercaptobenzimidazole, 5-ethoxy-2-mercaptobenzimidazole, and 2-mercaptoimidazoline with cinnamoyl chloride, its derivatives, and heteroanalogs was studied. Convenient methods were found for the synthesis of 2-aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-ones and 7-aryl-2,3,6,7-tetrahydro-5H-imidazo[2,1-b]-1,3-thiazin-5-ones.     

1,3,4-均三唑并[2,1-b]-1,3,4-噻二唑衍生物的合成及生物活性

以5-对甲苯基-1-氨基-2-巯基-1,3,4-均三唑和取代苯氧乙酰异硫氰酸酯为原料, 合成了10个未见文献报道的5-对甲苯基-2-取代苯氧乙酰氨基均三唑并[2,1-b]-1,3,4-噻二唑类化合物, 通过元素分析, 1H NMR, IR和MS确定化合物的结构, 初步生物活性测试表明目标化合物具有较好的除草活性.     

Synthesis of substituted 4H-thieno[2,3-b][1]benzothiopyran-4-ones as possible schistosomicidal agents

Summary A new series of thiophenic isosters of thioxanthones, namely: 2-substituted-4H-thieno[2,3-b][1]benzothiopyran-4-ones and 5-substituted-2-nitro-8-methyl-4H-thieno[2,3-b][1]benzothiopyran-4-ones were synthesized as potential schistosomicidal agents. The synthesized compounds were characterized by their¹H-NMR data.

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Synthese von substituierten 4H-Thieno[2,3-b][1]benzothiopyran-4-onen als mögliche schistosomicide Wirkstoffe

Zusammenfassung Es wurde eine neue Serie von thiophenischen Isosteren des Thioxanthons, nämlich 2-substituierte 4H-Thieno[2,3-b][1]benzothiopyran-4-one und 5-substituierte 2-Nitro-8-methyl-4H-thieno[2,3-b][1]benzothiopyran-4-one als potentielle schistosomicide Wirkstoffe synthetisiert. Die synthetisierten Verbindungen wurden mittels ihrer¹H-NMR Daten charakterisiert.

     

Deoxypegan-1-one derivatives. synthesis and borohydride reduction of 3-[(E)-arylmethylidene]-3,9-dihydropyrrolo[2,1-b]quinazolin-1(2H)-ones

3-[(E)-Arylmethylidene]-3,9-dihydropyrrolo[2,1-b]quinazolin-1(2H)-ones were prepared by reaction of quinazolyl-2-propionic acid hydrochloride with aromatic aldehydes in acetic anhydride in the presence of Et₃N. 3-[(E)-Arylmethylidene]-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazolin-1-ols were formed by reduction of the 3-arylidene derivatives with sodium borohydride in methanol, readily lost water when heated with acids, and were converted into 3-[(E)-arylmethylidene]-3,9-dihydropyrrolo[2,1-b]quinazolines. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 463–467, September–October, 2006.     

New 6-(4-Bromophenyl)-imidazo[2,1-b]thiazole Derivatives: Synthesis and Antimicrobial Activity

Summary.  New 4-alkyl/aryl-1-((6-(4-bromophenyl)-imidazo[2,1-b]thiazol-3-yl)-acetyl)-3-thiosemicarbazides and 3-alkyl/aryl-2-(((6-(4-bromophenyl)-imidazo[2,1-b]thiazol-3-yl)-acetyl)-hydrazono)-4-thiazolidinones were synthesized from 6-(4-bromophenyl)-imidazo[2,1-b]thiazole-3-acetic acid hydrazide. Their structures were elucidated by elemental analyses and spectroscopic data. All compounds were tested for antibacterial and antifungal activities. The antimicrobial activities of the compounds were assessed by the microbroth dilution technique. The compounds were also evaluated for antituberculosis activity against Mycobacterium tuberculosis H₃₇Rv (ATCC 27294); they exhibited varying degrees of inhibition in the in vitro primary screening at 6.25 μg · cm⁻³. The most active compound was 3-(4-nitrophenyl)-2-(((6-(4-bromophenyl)-imidazo[2,1-b]thiazol-3-yl)-acetyl)-hydrazono)-4-thiazolidinone. Corresponding author. E-mail: nurayulusoy@yahoo.com Received December 10, 2001. Accepted (revised) March 1, 2002     

纳米TiO_2催化一锅法合成喹唑啉酮并酞嗪酮及3-酰胺基异吲哚酮并喹唑啉酮类化合物

以纳米TiO_2为催化剂,靛红酸酐、2-甲酰基苯甲酸、不同芳香肼或酰肼类化合物为原料,在乙醇/水溶液为溶剂的条件下一锅法合成,高产率得到6个喹唑啉酮并酞嗪酮类化合物及10个3-酰胺基取代的异吲哚酮并喹唑啉酮类化合物.该方法简洁高效,反应条件温和,为喹唑啉酮并杂环类化合物的合成提供了一条新途径.     

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.     

p-Toluenesulfonic acid-catalyzed one-pot synthesis of 2-amino-4-substituted-1,4-dihydrobenzo[4,5]imidazolo[1,2-a]pyrimidine-3-carbonitriles under neat conditions

A simple, efficient, and green procedure for the preparation of 2-amino-4-substituted-1,4-dihydrobenzolo[4,5]imidazolo[1,2-a]pyrimidine-3-carbonitriles has been developed by multi-component condensation of 2-aminobenzimidazole with aldehydes and malononitrile in the presence of a catalytic amount of p-toluenesulfonic acid, affording excellent yields under neat conditions. The protocol avoids the use of expensive catalysts, toxic solvents, and chromatographic separation. We believe that this new environmentally metal-free procedure, combined to a solvent-free reaction, would be of importance in the search of green laboratory-scale synthesis.     

Synthesis of 3-acetyl-4-amino-6-arylpyran-2-ones and ethyl 7-aryl-4,5(1H,5H )-dioxopyrano[4,3-b]pyridine-2-carboxylates

The reactions of aroylacetonitriles with the nickel chelate of ethyl acetoacetate afforded new block heterocyclic reagents, viz., 3-acetyl-4-amino-6-arylpyran-2-ones. The reactions of the latter with diethyl oxalate gave rise to ethyl 7-aryl-4,5(1H,5H)-dioxopyrano[4,3-b]pyridine-2-carboxylates.     

Structure and Spectroscopic Studies of 4,8-bis(2-Hydroxybenzyl)-cis-octahydro[1,4]-oxazino [3,2-b]-1,4-oxazine

The title compound 4,8-bis(2-Hydroxybenzyl)-cis-octahydro [1,4]-oxazino [3,2-b]-1,4-oxazine (1) has been synthesized by the reaction of N-(2-hydroxybenzyl)-2-amino-1-ethanol with glyoxal. This novel compound was characterized by elemental analysis, IR, and ¹H NMR. The structure was also confirmed by a single crystal X-ray study. The compound crystallizes in monoclinic C2/C space group with unit cell dimensions: a = 18.318(4), b = 8.6110(17), c = 13.267(3) Å, = 119.90(3), V = 1814.1(6) ų, Z = 4. The two fused six-membered rings in 1 adopt chairlike conformations slightly flattened around the nitrogen atoms. In the central fusion bond, the geometry is a staggered conformation, with the two angular hydrogen atoms in the cis positions with respect to the rings, the nitrogen atoms antiperiplanar to each other, while the oxygen atoms remain gauche to each other and antiperiplanar to the hydrogen atoms. The ring conformations in 1 have been discussed on the basis of the anomeric effects and the presence of two strong intramolecular hydrogen bonds between the phenolic hydrogens and the amino groups.     

Synthesis and study of some properties of 1-aryl-2-oxo-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole 4-oxides

A number of 1-aryl-2-oxo-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole 4-oxides were synthesized based on 3-[N-aryl-N-(chloroacetyl)amino]-2-formylindoles. The nature of the substituent in the 1-aryl fragment has a pronounced influence on the course of reactions throughout the whole sequence of transformations during the synthesis of diazepinoindoles. The reduction of 4-oxides by formamidinosulfinic acid, hydrogen in the presence of Pd/C, and sodium bisulfite was studied. The structures of the reaction products were confirmed using IR and ¹H NMR spectroscopy and mass spectrometry.     

Synthesis and Structure Elucidation of Pyrimidobenzimidazoles and Fused Derivatives II [1]. Dodecahydrobenzimidazo-[2,1-b]quinazolines and Decahydrobenzimidazo-[2,1-b]benzo[h]quinazolines [2]

Summary.  The cyclization reactions of trans-3a-hexahydro-2-benzimidazolamine with 2-alkylidene- and 2-benzylidenecyclohexanones and α-tetralones, respectively, yield mixtures of two isomeric condensates each. Thorough high resolution NMR analyses (¹H and ¹³C NMR, HH-COSY, gs-HSQC, gs-HMBC, 1D TOCSY, and 1D NOE difference spectra) revealed that the corresponding isomers are in all cases linearly fused diastereomeric 12α- and 12β-substituted trans-6aα-dodecahydrobenzimidazo[2,1-b]quinazolines and 7α-substituted trans-8aβ- and trans-8aα-decahydrobenzimidazo[2,1-b]benzo[h]quinazolines, respectively. The formation of corresponding angularly fused regioisomers was not observed so far. The stereochemistry and the tautomerism of some bases and their hydrochlorides as well as the regiospecific course of the cyclization reactions are discussed. Biological tests showed that the novel compounds don’t exert remarkable antibacterial and antimycotic effects. Received November 3, 1999. Accepted November 30, 1999     

Synthesis and study of the mutagenic activity of di(indeno[2,1-b]indolyl)- and di(indeno[2,1-b]pyrrolyl)methanes and -dimethylsilanes

Dihetaryldimethylsilanes and dihetarylmethanes containing indeno[2,1-b]indolyl and indeno[2,1-b]pyrrolyl fragments were synthesized. Their mutagenic activity was tested according to Ames with standard test strains Salmonella typhimurium TA 1537, TA 98, and TA 100.     

Solid Phase Synthesis of 4H-Pyrimido[2,1-b] Benzothiazol-4-ones from Resin-Bound Cyclic Malonic Ester

The solid phase synthesis of 4H-pyrimido[2,1-6] benzothizaol-4-ones has been reported.     

Reaction of 6-methoxybenzo[b]furan-3(2H)-one and benzo[b]thiophen-3(2H)-one with 2-aryl-1,1-dicyanoethylenes as a convenient synthetic route to substituted 2-amino-4-aryl-1,3-dicyano-7-methoxydibenzo[b,d]furans and 2-amino-4-aryl-3-cyano-4H-benzothieno[3,2-b]pyrans

The reactions of 6-methoxybenzo[b]furan-3(2H)-one with 2-aryl-1,1-dicyanoethylenes and malononitrile or with aromatic aldehyde and two moles of malononitrile afford 2-amino-4-aryl-1,3-dicyano-7-methoxydibenzo[b,d]furans. The reactions of benzo[b]thiophen-3(2H)-one with 2-aryl-1,1-dicyanoethylenes or with aromatic aldehyde and one mole of malononitrile produce 2-amino-4-aryl-3-cyano-4H-benzothieno[3,2-b]pyrans.     

Synthesis of dibenzo[b,f][1,4]oxazepin-11(10H)-ones from 2-nitrobenzoic acids

Base-catalyzed intramolecular nucleophilic substitution for the 2-nitro group in 2-hydroxyanilides of 2-nitrobenzoic acids gave dibenzo[b,f][1,4]oxazepin-11(10H)-ones. In particular, 3-nitrodibenzo[b, f][1,4]oxazepin-11(10H)-one was obtained from N-(2-hydroxyphenyl)-2,4-dinitrobenzamide. The nitro group in the product could also be replaced under the action of O- and S-nucleophiles. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 529–533, March, 2006.