Reduction of (<Emphasis Type="Italic">E</Emphasis>)-3-aryl-2-(thiazol-2-yl)acrylonitriles with lithium aluminum hydride

Reduction of (E)-3-aryl-2-(4-arylthiazol-2-yl)acrylonitriles with lithium aluminum hydride in dry ether afforded (Z)-1-amino-3-aryl-2-(thiazol-2-yl)prop-1-ene derivatives in 15 to 40% yields. The structure of (Z)-1-amino-3-(2-chlorophenyl)-2-[4-(4-methylphenyl)thiazol-2-yl]prop-1-ene was confirmed by X-ray diffraction analysis. Dedicated to Academician N. K. Kochetkov on the occasion of his 90th birthday. __________ Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1301–1303, May, 2005.     

Synthesis of 3-[4-(1-Benzofuran-2-yl)-1,3-thiazol-2-yl]-2-(4-aryl)-1,3-thiazolidin-4-one Derivatives as Biological Agents

A protocol for the synthesis of 3-[4-(1-benzofuran-2-yl)-1,3-thiazol-2-yl]-2-(4-aryl)-1,3-thiazolidin-4-one derivatives (5a–e) has been developed from 1-(1-benzofuran-2-yl)-2-bromoethanone (2),which served as a key intermediate for the synthesis of the title compounds. The reaction of compound 2 with thiourea furnished 4-(1-benzofuran-2-yl)-1,3-thiazol-2-amine 3, which upon further reaction with various aromatic aldehydes, gave Schiff bases 4a–e. These Schiff bases, when treated with thioacetic acid in the presence of catalytic amount of anhydrous ZnCl₂, yielded thiazolidinone derivatives 5a–e. All the newly synthesized compounds have been characterized by analytical and spectral data and screened for their antimicrobial and analgesic activity.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Reactions of N,N-Disubstituted 5-Arylmethylidene-2-amino-thiazol-4(5H)-ones with CH Acids

Summary.  N,N-Disubstituted 5-arylmethylidene-2-aminothiazol-4(5H)-ones reacted with diethyl malonate, ethyl benzoylacetate, acetylacetone, or cyclopentadiene in refluxing toluene and in presence of powdered sodium to give the respective 5-arylmethylidene-2′-amino-2,5′-bithiazolylidene-4,4′-dione derivatives in moderate yields. 5-Benzylidene-2-morpholin-4-yl-2-thiazol-4(5H)-one reacted with malononitrile in toluene and in presence of powdered sodium under mild conditions to afford the 1:1 adduct, benzylmalononitrile, and 2-morpholin-4-yl-2-thiazol-4(5H)-one. However, similar treatment of 5-(4-methoxyphenylmethylidene)-2-morpholin-4-yl-2-thiazol-4(5H)-one with malononitrile yielded the 2,5′-bithiazolylidene-4,4′-dione derivative together with 4-methoxyphenylmethylidene malononitrile. Treatment of 5-benzylidene- and 5-(4-methoxyphenylmethylidene)-2-morpholin-4-yl-2-thiazol-4(5H)-ones with 3-phenyl-4-oxo-2-thioxo-1,3-thiazolidine in refluxing toluene and in presence of powdered sodium produced 5-arylmethylidene-3-phenyl-4-oxo-2-thioxo-1,3-thiazolidines in good yields. The structures of all products were deduced from microanalytical and spectroscopic data, mechanistic details are discussed. Corresponding author. E-mail: kamalkandeel@hotmail.com Received November 5, 2001. Accepted (revised) December 17, 2001     

Synthesis and structures of 5(3H)-oxotetrahydro-1H-imidazo[4,5-c][1,2,5]thiadiazole 2,2-dioxides

The reactions of sulfamides with 4,5-dihydroxyimidazolidin-2-ones were studied at ambient and high pressure. The previously unknown derivatives of 5(3H)-oxotetrahydro-1H-imidazo-[4,5-c][1,2,5]thiadiazole 2,2-dioxide, viz., sulfo analogs of tetrahydroimidazo[4,5-d]imidazole-2,5-(1H,3H) diones (glycolurils), were synthesized. The structures of some of these compounds were established by X-ray diffraction. The high-pressure reactions performed under conditions of solvent phase transitions afforded also N-(1,3-diethyl-5-hydroxy-2-oxoimidazolidin-4-yl)-N,N′-dialkylsulfamides. Among these compounds, a new conglomerate was found. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1711–1719, May, 2008.     

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.     

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     

Alternative products in one-pot reaction of benzylidenemalononitrile,N-methyl-2-thiocarbamoylacetamide,and ω-bromoacetophenone

N-Methyl-2-benzoylmethylsulfanyl-4-phenylnicotinamide and N-methyl-2-(4-phenyl-1,3-thiazol-2-yl)-acetamide have been obtained as alternative products to the desired N-methyl-2,3-dihydro-7H-thiazolo[3,2-a]pyridine-8-carboxamide by a one-pot cyclocondensation of benzylidenemalononitrile, N-methyl-2-thiocarbamoylacetamide, piperidine, and ω-bromoacetophenone. 2-Amino-1-methyl-6-oxo-4-phenyl-5-(4-phenyl-1,3-thiazol-2-yl)-1,6-dihydropyridine-3-carbonitrile has been obtained as main product by treatment of benzylidenemalononitrile with N-methyl-2-(1,3-thiazol-2-yl)acetamide. Dedicated to Professor I. Kalvinsh on his 60th birthday __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 777–781, May, 2007.     

Synthese und Reaktionsverhalten von 3-(Bis(alkylthio)methylen)-3H-isobenzofuran-1-on-und 2-(Bis(alkylthio)methylen)-3(2H)-benzofuranon-Derivaten

Summary 3(Bis(alkylthio)methylene)-3H-isobenzofuran-1-ones2a–e and 2-(bis(alkylthio)methylene)-3(2H)-benzofuranone derivatives4a–c are obtained by reaction of phthalides1a–d or 3(2H)-benzofuranone (coumaranone3), respectively, with carbon disulfide under basic conditions followed by alkylation. The reaction behaviour of the new compounds2 and4 is investigated. 2-((2-Dimethylthio-1-oxo)ethyl)benzoic acid N,N-dimethylamide (7a) and 2-((2-dimethylthio-1-oxo)ethyl)-benzoic acid 2-methylpiperidide (7b) are surprisingly formed instead of the methylthio substitution products by treatment of2a with the corresponding amine in the presence of aluminum chloride.

Herrn Professor Dr. Dr. h. c.Waldemar Adam zum 60. Geburtstag gewidmet     

4-(3-Cyanopyridin-2-ylthio)acetoacetates in synthesis of heterocycles

Substituted 2-amino-4-aryl-3-cyano-5-oxo-5,6-dihydro-4H-pyrano[2,3-d]pyrido[3",2":4,5]thieno[3,2-b]pyridines were synthesized by the reactions of 4-hydroxy-1H-thieno[2,3-b;4,5-b]dipyridin-2-ones with arylidenemalononitriles or by the three-component reactions of hydroxythienodipyridinones with aldehydes and malononitrile in DMF in the presence of triethylamine. Methods for syntheses of substituted 3-alkoxycarbonyl-6-amino-4-aryl-2-(3-cyanopyridin-2-ylthiomethyl)-4H-pyrans were developed on the basis of the reactions of 4-(3-cyanopyridin-2-ylthio)acetoacetates and arylidenemalononitriles or aldehydes and malononitrile. Ethyl 4-(3-cyanopyridin-2-ylthio)acetoacetate and 4-methoxybenzylidenecyanothioacetamide were used for the synthesis of 6-(pyridin-2-ylthiomethyl)-3-cyanopyridine-2(1H)-thione.     

The reactions of aroylpyruvic acids and their derivatives witho-aminophenyldiphenylmethanol

Aroylpyruvic acids and their methyl esters react witho-aminophenyldiphenylmethanol to form 4-aryl-2-[2-(1-hydroxydiphenylmethyl)phenylamino]-4-oxobut-2-enoic acids and their esters. The α-enamino acids obtained undergo intramolecular heterocyclization in the presence of Ac₂O to affort substituted 4,5-dihydrobenzo[e][1,4]oxazepin-3(1H)-ones. The reaction of 5-arylfuran-2,3-diones witho-aminophenyldiphenylmethanol leads to products of decyclization, 2-(1-hydroxydiphenylmethyl)phenylamides of 4-aryl-2-hydroxy-4-oxobut-2-enoic acid, which upon heating in AcOH or Ac₂O yield 3-aroylacetyl-1,1-diphenyl-1H-benzo[d][1,3]oxazines. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2317–2319, November, 1998.     

A convenient and new approach to the synthesis of ω-heterocyclic amino acids from carboxy lactams through ring-chain-transformation. Part 2: Synthesis of (2R)-/(2S)-2-aminomethyl-3-(1-aryl-/1,5-diaryl-1H-pyrazol-3-yl)-propionic acid

Making use of amide activation, a convenient and short path synthesis of optically pure ω-heterocyclic-β-amino acids has been achieved from (1R,3R)- and (1R,3S)-5-oxo-1-(1-phenyl-ethyl)-pyrrolidine-3-carboxylic acid methyl ester. The key step of the synthesis involves a regiospecific ring-chain-transformation of the enaminones when subjected to 1,2-binucleophilic attacks. The method is illustrated by the synthesis of (2R)-/(2S)-2-aminomethyl-3-(1-aryl-/1,5-diaryl-1H-pyrazol-3-yl)-propionic acid.     

Guanidine and amidine mediated synthesis of bridgehead triazaphenalenes, pyrimidines and pyridines through domino reactions

An efficient and concise synthesis of 8-amino-2,5-diaryl-1,9,9b-triazaphenalene-4-carbonitriles has been delineated through two successive base catalyzed heteroaromatic annulations of 6-aryl-4-(piperidin-1-yl)-2H-pyran-2-one-3-carbonitriles by guanidine hydrochloride in moderate yield. This reaction was further explored through the ring transformation of 4 with amidines 8 and 11 to afford (2,6-diarylpyrimidin-4-yl)acetonitriles and 6-aryl-4-(piperidine-1-yl)nicotinonitriles in excellent yields.     

Synthesis and fungicidal activities of 1-[(2,2-diaryl-1,3-dioxolan-4-yl)methyl]-1H-azoles

Ketalization of benzophenones with epichlorohydrin or 3-chloropropane-1,2-diol gave 2,2-diaryl-4-chloromethyl-1,3-dioxolanes, which were used to alkylate sodium salts of imid-azole or 1,2,4-triazole. The resulting 1-[(2,2-diaryl-1,3-dioxolan-4-yl)methyl]-1H-azoles exhibit high fungicidal activities. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 940–944, May, 2007.     

The (E)/(Z)-ratio in the reaction of 5-(2-aryl-2-oxoethyl)-2-thioxo-4-oxo-1,3-thiazolidines with bromine

Summary 3-Aryl-, 3-benzyl-, and 3H-5-(2-aryl-2-oxoethyl)-2-thioxo-4-oxo-1,3-thiazolidines3a–h react with bromine in acetic acid solution to give mixtures of the respective 5-aroylmethylene (E) and (Z) diastereomeric derivatives5 and6. They contain more than 85% of the (E)-diastereomers along with some pure isomers. The intermediacy of the 5-bromo derivatives4 is proven and a plausible route of the reaction is presented. Structures of compounds3–6 are evidenced by analytical and spectral data.

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Das Verhältnis von (E)- und (Z)-Isomeren bei der Reaktion von 5-(2-Aryl-2-oxomethyl)-2-thioxo-4-oxo-1,3-thiazolidinen mit Brom

Zusammenfassung 3-Aryl-, 3-Benzyl- und 3H-5-(2-Aryl-2-oxoethyl)-2-thioxo-4-oxo-1,3-thiazolidine3a–h reagieren mit Brom in essigsaurer Lösung zu Gemischen der entsprechenden diastereomeren 5-Arylmethylen-Derivate ((E) und (Z))5 und6. Sie enthalten mehr als 85% des (E)-Diastereomeren. Die intermediäre Natur der 5-Brom-Derivate4 wird bewiesen; ein Reaktionsweg wird vorgeschlagen. Die Strukturen der Verbindungen3–6 werden durch analytische und spektroskopische Daten abgesichert.

     

Synthesis of 5-Amino-1-aryl-4-(4-aryl-1,3-thiazol-2-yl)- 2,3-dihydro-1H-pyrrol-3-ones*

Reactions of 2-(4-aryl-1,3-thiazol-2-yl)-3-oxo-4-chlorobutyronitriles with primary aromatic amines result in nucleophilic substitution of the chlorine atom by amino group, followed by intramolecular addition of the secondary amino group to the cyano group. The products are 5-amino-1-aryl-4-(4-aryl-1,3-thiazol-2-yl)- 2,3-dihydro-1H-pyrrol-3-ones which are structurally related to the known antiischemic drugs.     

Synthesis of 3-(trifluoromethyl)indeno[2,1-c]pyran-1,9-diones from 4-aryl-3-carbethoxy-6-(trifluoromethyl)-2-pyrones and their reaction with sodium azide leading to new carbostyril derivatives

Treatment of ethyl 4-aryl-6-(trifluoromethyl)-2-oxo-2H-pyran-3-carboxylates, prepared from 4,4,4-trifluorobutane-1,3-diones, PCl₅ and sodium diethyl malonate, with sulfuric acid afforded the intramolecular Friedel–Crafts acylation products, 3-(trifluoromethyl)indeno[2,1-c]pyran-1,9-diones, from which 2-(trifluoromethyl)-6H-pyrano[3,4-c]quinoline-4,5-diones were obtained via the Schmidt reaction in moderate yields. The latter reacted with sodium azide to give 2-oxo-4-(5-trifluoromethyl-1,2,3-triazol-4-yl)-1,2-dihydroquinoline-3-carboxylic acids in good yields.     

Synthesis of 1H-1,2,3-triazole derivatives by the cyclization of aryl azides with 2-benzothiazolylacetonone, 1,3-benzo-thiazol-2-ylacetonitrile,and (4-aryl-1,3-thiazol-2-yl)acetonitriles

The cyclization of aryl azides with 2-benzothiazolylacetone, 1,3-benzothiazol-2-ylacetonitrile, and (4-aryl-1,3-thiazol-2-yl)acetonitriles in methanol in the presence of sodium methylate gives high yields of new products, 2-(5-methyl(amino)-1-aryl-1H-1,2,3-triazol-4-yl)-1,3-benzothiazoles and 1-aryl-(4-aryl-1,3-thiazol-2-yl)-1H-1,2,3-triazole-5-amines. 1,3-Benzothiazol-2-ylacetonitrile undergoes an anionic domino reaction with methyl 2-azidobenzoate or 2-azidobenzonitrile to give [1,2,3]triazolo[1,5-a]quinazoline derivatives. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 612–618, April, 2009.     

Tri-component reaction of 2-alkyl-4,5-dichloropyridazin-3(2H)-ones: synthesis of 5-cyano-5-(pyrimidin-2-yl)-2,7-dialkyl-5H-dipyridazino-[4,5-b:4,5-e]-4H-thiopyran-1,6-dione and 2-(4-cyanophenoxy) pyrimidine

Reaction of 2-alkyl-4,5-dichloropyridazin-3(2H)-ones with p-cyanophenol and 2-mercaptopyrimidine in the presence of base gave 2,4,5-trisubstituted-pyridazin-3(2H)-ones 4-9, 2-(4-cyanophenoxy)pyrimidine (10) and 5-cyano-5-(pyrimidin-2-yl)-2,7-dialkyl-5H-dipyridazino[4,5-b:4,5-e]-4H-thiopyran-1,6-diones 11 as a novel heterocycle.     

A novel and facile synthesis of 2-(cyclohexylamino)-6,7-dihydro-3-aryl-1H-indole-4(5H)-ones via a one-pot multi-component reaction

A simple and efficient synthesis of 2-(cyclohexylamino)-6,7-dihydro-3-aryl-1H-indole-4(5H)-ones was achieved via a one-pot multi-component reaction of cyclohexyl isocyanide, an aldehyde, a 1,3-dicarbonyl compound, and ammonium acetate in the presence of a catalytic amount of KHSO₄ in acetonitrile.     

Facile Synthesis of 6-Aryl-3-cyanopyridine-2-(1H)-thiones from Aryl Ketones

An improved synthesis of 6-aryl-3-cyanopyridine-2-(1H)-thiones utilizing enaminones as starting materials catalyzed by 1,4-diazabicyclo[2.2.2]octane (DABCO) was described. Moreover, a convenient one-pot conversion of aryl ketones to 6-aryl-3-cyanopyridine-2-(1H)-thiones was also developed in moderate to good yields (up to 80%).