Synthesis and alkylation of 1-substituted 3-thioxo-2,3,5,6,7,8-hexahydroisoquinoline-4-carbonitriles

The condensation of cyclohexylidene(cyano)thioacetamides with aldehydes or of 2-acyl-1-(morpholin-4-yl)cycloalkenes with dithiomalonamide gave 1-alkyl(aryl)-3-thioxo-2,3,5,6,7,8-hexahydroisoquinoline-4-carbonitriles. Reactions of the latter with various alkylating agents selectively produced the corresponding isoquinolin-3-yl sulfides or products of their subsequent Thorpe cyclization, thieno[2,3-c]isoquinolines.     

Indole derivatives CXV. Synthesis and some transformations of 5-(3-indolyl)isoxazole-3-carboxylic acid

5-(3-Indolyl)isoxazole-3-carboxylic acid and its amide and hydrazide were obtained from ethyl 5-(3-indolyl)isoxazole-3-carboxylate. When 5-(3-indolyl)isoxazole-3-carboxylate is heated, it undergoes decarboxylation with isomerization to 3-(-cyanoacetyl)indole; when it is heated in alcohol with hydrazine and phenylhydrazine in the presence of copper, it undergoes isomerization to 5-(3-indolyl)pyrazole-3-carboxylic and 1-phenyl-5-(3-indolyl)-pyrazole-3-carboxylic acids. 5-(3-Indolyl)pyrazole-3-carboxylic acid hydrazide is formed when a solution of ethyl 5-(3-indolyl)isoxazole-3-carboxylate is refluxed with hydrazine in 96% alcohol.See [1] for communication CXIV.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 936–938, July, 1978.     

Synthesis of 1-(9-butylcarbazol-3-yl)-5-oxopyrrolidine-3-carboxylic acid derivatives

A series of condensation products of 1-(9-butylcarbazol-3-yl)-5-oxopyrrolidine-3-carbohydrazide with 2-propanone, 2-butanone, 2,4-pentanedione, 2,5-hexanedione, ethyl 3-oxobutanoate, and aromatic aldehydes was obtained. Substituted oxadiazoles were synthesized from carbohydrazide or the corresponding hydrazone. Spectral properties of the synthesized compounds were examined. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1009–1017, July, 2008.     

Synthesis and hydrolytic cleavage of 1-aryl-5-cyano-6-(2-dimethylaminovinyl)-4-oxo(thioxo)-1,4-dihydropyrimidines

1-Aryl-5-cyano-6-(2-dimethylaminovinyl)-4-oxo-1,4-dihydropyrimidines and their 4-thioxo analogs, which were prepared in three steps from cyanoacetamide and cyanothioacetamide, respectively, were subjected to hydrolysis. In aqueous AcOH, hydrolysis of N-(dimethylaminomethylene)-2-cyano-5-dimethylamino-2,4-pentadieneamide derivatives containing amino groups at position 3 afforded formylpyridones. The reaction of 2-cyano-3-dimethylaminothiocrotonamide with DMF dimethyl acetal gave rise to 3-cyano-4-dimethylamino-2-methylthiopyridine.     

Synthesis and transformations of derivatives of 2-aryl-5-(3,5-dimethyl-1H-pyrazol-1-yl)-1,3-oxazole-4-carboxylic acid

On the basis of methyl esters of 2-aryl-5-hydrazino-1,3-oxazole-4-carboxylic acids the earlier unknown methyl esters of 2-aryl-5-(3,5-dimethyl-1H-pyrazol-1-yl)-1,3-oxazole-4-carboxylic acids as well as their functional derivatives were synthesized. The latter were used for further transformations, in particular, for introducing the residues of highly basic aliphatic amines into the 5 position of oxazole, and the oxazol-2-yl moiety into the 4 position of the oxazole ring.     

Synthesis and antimycobacterial screening of new 4-(4-(1-benzyl-1H-1,2,3-triazol-4-yl)-1-phenyl-1H-pyrazol-3-yl)quinoline derivatives

A new series of 4-(4-(1-benzyl-1H-1,2,3-triazol-4-yl)-1-phenyl-1H-pyrazol-3-yl)quinoline ( 6a-t ) have been synthesized by a click reaction of 4-(4-ethynyl-1-phenyl-1H-pyrazol-3-yl)quinoline ( 4a-d ) with a substituted benzyl azide ( 5a-e ). The starting alkyne derivatives 4a-d are obtained from Bestmann-Ohira reaction of 1-phenyl-3-(quinolin-4-yl)-1H-pyrazole-4-carbaldehyde and dimethyl(1-diazo-2-oxopropyl)phosphonate. The newly synthesized compounds are screened against M. tuberculosis H37Ra dormant and active, Escherichia coli, Pseudomonas fluorescence, Staphylococcus aureus and Bacillus subtilis strains at 30 μg/mL concentration. Most of the screened compounds showed good to moderate antibacterial activity against S. aureus, B. subtilis, and Mycobacterium tuberculosis H37Ra strains. The synthesized derivatives of quinolinyl-pyrazole-4-carbaldehyde and quinolinyl-pyrazole-4-ethyne reportd good to moderate activity against both strains of M. tuberculosis H37Ra. Ten derivatives of quinolinyl-pyrazole presented good activity against B. subtilis. These results suggested that further optimization and development of quinolinyl-pyrazolyl-1,2,3-triazole moeity could serve as lead compounds for antimycobacterial activity.     

基于2-(4-二羟基硼烷)苯基喹啉-4-羧酸的二硼酸化合物的合成

以4-溴苯乙酮、靛红及常见试剂为起始原料,通过Pfitzinger reaction、羧基酯化、钯催化、水解等反应合成2-(4-二羟基硼烷)苯基喹啉-4-羧酸(PBAQA).二胺化合物经二碳酸二叔丁酯单保护、酰胺缩合、盐酸脱保护基,再与另一端苯基硼酸化合物酰胺缩合,合成了3个含有PBAQA结构的二硼酸新化合物,考察了溶剂选择、反应温度、活化反应时间以及反应中羧基化合物与1,3-二环己基碳化二亚胺(DCC)和1-羟基苯并三唑(HOBT)物质的量之比对二硼酸类化合物收率的影响.通过IR、~1H NMR、~(13)C NMR、HRMS对新化合物的结构进行表征.结果表明最佳反应条件为以N,N-二甲基甲酰胺(DMF)作溶剂,反应温度20℃,活化反应60 min,反应中羧基化合物与DCC和HOBT的物质的量之比在1∶20∶20的条件下,收率可达82%,纯度90%.该合成路线具有操作步骤简便,经济适用,副产物少易于纯化等特点,对二硼酸化合物衍生化研究具有重要实用和经济价值.     

New 4-quinaldinol derivatives XVII. 2-Methyl-3-(3-chloro-2-buten-1-yl)-4-hydroxyquinoline-6-carboxylic acid and some of its transformations

1-(2-Methyl-4-hydroxy-6-carboxy-3-quinolinyl)-3-butanone and 1-(2-methyl-4-chloro-6-carboxy-3-quinolinyl)-3-butanone were obtained by the acid hydrolysis of 2-methyl-3-(3-chloro-2-buten-1-yl)-4-hydroxy(chloro)quinoline-6-carboxylic acids and their esters.See [6] for communication XVI.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1681–1682, December, 1971.     

Synthesis and properties of derivatives of 4-aminofuroxan-3-carboxylic acid

4-Amino-3-cyanofuroxan, obtained by the oxidation of aminocyanoglyoxime, reacts with hydrazine and hydroxylamine to form the amidrazone and amidoxime respectively of 4-aminofuroxan-3-carboxylic acid. The reaction of the amidoxime with triethyl orthoformate can lead to closure of both the pyrimidine and the 1,2,4-oxadiazole ring.Latvian Institute of Organic Synthesis, Riga. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1115–1119, August, 1997.     

Synthesis of new derivatives of 6-(1-adamantylmethyl)-4(3H)-pyrimidinone

Russian Journal of Organic Chemistry -     

Synthesis of some new pyrazolyl-thiazolidinone derivatives starting from 1-(3-chlorophenyl)-3-(4-methoxyphenyl)-1H-pyrazole-4-carboxaldehyde

Russian Journal of General Chemistry - A novel synthetic approach to (E)-1-{[1-(3-chlorophenyl)-3-[(4-methoxyphenyl-1H-pyrazol-4-yl)- methylene]hydrazono}-3-phenylthiazolidin-4-one starting from...     

Synthesis and structure of [2-oxo(thioxo)tetrahydropyrimidin-4-yl]calix[4]arenes

Cone-shaped di- and tetrapropoxycalix[4]arenes functionalized at the upper rim with one or two 2-oxo(thioxo)tetrahydropyrimidine residues were synthesized by the Biginelli reaction of formylcalixarenes with urea (thiourea) and methyl acetoacetate. The steric structure of the products was studied by NMR and X-ray diffraction. The Biginelli reaction with dipropoxyformylcalixarene was diastereoselective, and it quantitatively produced the corresponding meso form. Tetrapropoxydiformylcalixarenes under analogous conditions gave rise to equimolar mixtures of racemic and meso compounds. The macrocyclic skeleton of the synthesized pyrimidine-containing calixarenes in crystal and in solution has a flattened cone conformation. (5-Methoxycarbonyl-2-oxotetrahydropyrimidin-4-yl)calixarene molecules in crystal undergo self-organization to form infinite chains via repeated inclusion of the methoxy group into the cavity of the neighboring macrocycle. Selforganization of bis(5-methoxycarbonyl-2-oxotetrahydropyrimidin-4-yl)calixarene with formation of analogous chains involves intermolecular hydrogen bonding NH ... O=C.     

A study of the Claisen rearrangement of 7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one derivatives

Summary The Claisen rearrangement of 7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (2 a) gave 7-hydroxy-8-(1-phenyl-2-propenyl)-3-phenyl-(4H)-1-benzopyran-4-one (3 a) and 2,3-dihydro-2,6-diphenyl-3-methyl-(7H)furo[2,3-h]-1-benzopyran-7-one (7 a). 2-Methyl-7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (2 b) afforded4 b and7 b. 8-Methyl-7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (12) gave only the alkali soluble product 7-hydroxy-8-methyl-6-(1-phenyl-2-propenyl)-3-phenyl-(4H)-1-benzopyran-4-one (13).3 a,4 b, and13 were further cyclized in acidic medium to9 a,10 b, and14 followed by dehydrogenation.This paper is dedicated to Dr. F. M. Dean, Department of Organic Chemistry, Robert Robinson Laboratories, University of Liverpool, Liverpool, U. K., on his retirement     

5-(4-氯苯基)-1-(2,4-二氯苯基)-4-甲基吡唑-3-羧酸的合成

对氯苯丙酮经三甲基氯硅烷保护后与草酸单乙酯单酰氯缩合制得4-(4-氯苯基)-3-甲基-2,4-二氧代丁酸乙酯(4);4与2,4-二氯苯肼盐酸盐缩合成腙、再经分子内环合、水解合成了制备利莫那班的关键中间体——5-(4-氯苯基)-1-(2,4-二氯苯基)-4-甲基吡唑-3-羧酸,总收率30.3%,其结构经1HNMR和MS确证。     

Synthesis of new acridine-9-carboxylic acid derivatives

New 1,3-dihydroxyacridine-9-carboxylic acids were obtained by Pfitzinger reaction from 2,4,6-trihydroxytoluene (methylphloroglucinol). Their bromination and azo-coupling reactions were studied. Computer simulation was used to determine potential pharmacokinetic and toxic properties of the synthesized compounds.