Synthesis of 5-substituted 1-aryl-1H-pyrazole-4-acetonitriles, 4-methyl-1-phenyl-1H-pyrazole-3-carbonitriles and pharmacologically active 1-aryl-1H-pyrazole-4-acetic acids

Lithium aluminum hydride reduction of 5-substituted or unsubstituted ethyl or methyl 1-aryl-1H-pyrazole-4-carboxylates gave, generally in excellent yields, 5-substituted or unsubstituted 1-aryl-1H-pyrazole-4-methanols which afforded the corresponding 1-aryl-4-(bromomethyl)-1H-pyrazoles with hydrobromic acid in acetic acid solution. These crude intermediates gave by reaction with potassium cyanide in dimethylsulfoxide solution 1-aryl-1H-pyrazole-4-acetonitriles only in the case of 5-unsubstituted compounds, otherwise mixtures of 5-substituted 1-aryl-1H-pyrazole-4-acetonitriles and 4-methyl-1-phenyl-1H-pyrazole-3-carbonitriles were generally obtained. Acetonitriles IIIa,b,i,l gave in excellent yields the corresponding 1-aryl-1H-pyrazole-4-acetic acids Va,b,i,l by alkaline hydrolysis. Compounds Vb,i,l showed in the writhing test appreciable analgesic properties, associated with low acute toxicity; moreover, compound VI exhibited a statistically significant antiinflammatory activity in the carrageenan-induced edema assay.     

Polyfunctional imidazoles: VI. Synthesis of 2-amino-1-aryl-4-chloro-1H-imidazole-5-carboxylic acids derivatives

Aryl-2,4-dichloro-5-formylimidazoles by a successive treatment with hydroxylamine and thionyl chloride were converted into 1-aryl-2,4-dichloroimidazole-5-carbonitriles which by the action of sodium azide and tin(II) chloride were transformed into 2-amino-1-aryl-4-chloroimidazole-5-carbonitriles. The consecutive reactions of 2-azido-1-aryl-4-chloro-5-formylimidazoles with N-bromosuccinimide, methanol, or amides led to the formation of methyl esters and amides of 2-azido-1-aryl-4-chloroimidazole-5-carboxylic acids. The reduction of the latter with tin(II) chloride resulted in the corresponding derivatives of 2-amino-1-aryl-4-chloroimidazole-5-carboxylic acids, and the reduction of 2-azido-1-aryl-4-chloroimidazole-5-carboxylic acids was accompanied with decarboxylation and yielded 2-amino-1-aryl-4-chloroimidazoles.     

Synthesis of 4-aryl-6-indolylpyridine-3-carbonitriles and evaluation of their antiproliferative activity

A novel class of 6-indolypyridine-3-carbonitrile derivatives were synthesized and evaluated for antiproliferative activities to establish structure–activity relationship. The synthesis was carried out through one-pot multicomponent reaction of 3-acetylindole, aromatic aldehydes, ethyl cyanoacetate, and ammonium acetate in the presence of piperidine as a catalyst, using a microwave irradiation method or a traditional thermal method. This was followed by chlorination for compounds 13a–e and subsequent nucleophilic substitution of the chlorine group by ethylenediamine at C₂ position of the pyridine ring. The antiproliferative activity of these new nicotinonitriles was evaluated against human ovarian adenocarcinoma (SK-OV-3), breast adenocarcinoma (MCF-7), and cervix adenocarcinoma (HeLa) cells. Among all compounds, 2-((2-aminoethyl)amino)-4-aryl-6-indolylnicotinonitriles series (15a, 15b, 15d, and 15e) exhibited higher antiproliferative activity on the three cancer cell lines with IC₅₀ values of 4.1–13.4 μM.     

1-(2-氨基-3,5-二氰基-4-芳基-4H-吡喃-6-基)愈创兰烃薁的合成

在醋酸铵作用下,通过1-氰乙酰基愈创兰烃薁、芳香醛、丙二腈的三组分反应,一锅法合成了一系列1-(2-氨基-3,5-二氰基-4-芳基-4H-吡喃-6-基)愈创兰烃薁衍生物.该反应操作简单、条件温和、收率良好.产物结构经NMR,MS,IR及元素分析等得以证实.     

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.     

Convenient Ultrasound-Promoted Regioselective Synthesis of Fused 6-Amino-3-methyl-4-aryl-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile

A multicomponent, catalyst-free reaction for the synthesis of fused 6-amino-3-methyl-4-aryl-1H-pyrazolo [3,4-b] pyridine-5-carbonitrile from 3-amino-5-methylpyrazole, malononitrile, and substituted aldehydes under ultrasound irradiation in short reaction times (8–10 min) with good yields (85–98%) is reported.

热敏共聚物负载的2-氨基-3-氰基-4-取代苯基-5-甲氧羰基-4H-吡喃化合物的合成

以具有热敏性能的N-异丙基丙烯酰胺及其衍生物的共聚物作载体,利用温度为相分离的控制手段,在水介质中合成了2-氨基-3-氰基-4-取代苯基-5-甲氧羰基-4H-喃化合物,其结构经^1H NMR,IR和元素分析确证。     

微波促进下6-氨基-4-芳基-5-氰基-3-甲基-1-苯基吡啶[2,3-c]并吡唑的合成

5-氨基-3-甲基-1-苯基吡唑与芳亚甲基丙二腈在少量乙二醇中, 经微波辐射得到6-氨基-4-芳基-5-氰基-3-甲基-1-苯基吡啶[2,3-c]并吡唑衍生物, 反应4～8 min完成, 产率为71%～90%, 产物结构通过红外、核磁共振、元素分析及单晶X射线分析表征.     

5-Amino-4,5-dihydroisoxazoles. Part I. 5-Amino-3-aryl-4-methylene-4,5-dihydroisoxazoles and 4-aminomethyl-3-arylisoxazoles from 5-amino-4-aminomethyl-3-aryl-4,5-dihydroisoxazoles

5-Amino-4-aminomethyl-3-aryl-4,5-dihydroisoxazoles 2 were obtained by cycloaddition of nitrile oxides to 1,3-diaminopropenes 1. On reaction with methyl iodide the corresponding 4-(quaternary)-ammoniomethyl iodides 3 were formed. These compounds, on reaction with bases, afforded 5-amino-3-aryl-4-methylene-4,5-dihydroisoxazoles 4. The acid-catalyzed deamination of compounds 2 afforded 4-aminomethyl-3-arylisoxa-zoles 5 and 3-arylisoxazoles as retro-Mannich products. The deamination of 2 to yield 5 was also obtained by base catalysis.     

Synthesis of 6-amino-4-aryl-3-methyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitriles by heterogeneous reusable catalysts

A new, efficient and environmentally benign protocol for the one-pot, four-component synthesis of 1,4-dihydropyrano[2,3-c]pyrazoles by reaction of hydrazine monohydrate, ethyl acetoacetate, arylaldehydes and malononitrile in the presence of a green catalytic amount of P₂O₅/SiO₂, H₃PO₄/Al₂O₃, cellulose sulfuric acid and starch sulfuric acid is described. The use of non-toxic and inexpensive materials, simple and clean work-up, short reaction times and good yields of the products are the advantages of this method.     

微波促进下2-氨基-3-氰基-4-芳基-4H- 吡喃化合物的一锅法合成

标题化合物可在微波辐射下以良好的产率经一锅法合成，为2-氨基-4H-吡哺类化合物的制备提供了一种快速便捷的有效方法。     

Synthesis and Antibacterial Activities of 4-Amino-3-(1-aryl-5-methyl-1,2,3-triazol-4-yl)-5-mercapto-1,2,4-triazoles/2-Amino-5-(1-aryl-5-methyl-1,2,3-triazol-4-yl)-1,3,4-thiadiazoles and Their Derivatives

ＩｎｔｒｏｄｕｃｔｉｏｎＳｃｈｉｆｆｂａｓｅｓ ,ａｍｉｄｅｓ ,ｉｍｉｄａｚｏｌｏ[2 ,1 ｂ] 1,3,4 ｔｈｉａｄｉａｚｏｌｅｓ,ａｎｄ 7Ｈ ｓ ｔｒｉａｚｏｌｏ[3,4 ｂ] 1,3,4 ｔｈｉａｄｉ ａｚｉｎｅｓｃｏｎｔａｉｎｉｎｇｈｅｔｅｒｏｃｙｃｌｅｓｈａｖｅｂｅｅｎａｔｔｒａｃｔｉｎｇｍｕｃｈａｔｔｅｎｔｉｏｎａｓｐｏｔｅｎｔｉａｌａｎｔｉｆｕｎｇａｌａｇｅｎｔｓ .1 51,2 ,3 ｔｒｉａ ｚｏｌｅ ,6 7ｍｅｒｃａｐｔｏ 1,2 ,4 ｔｒｉａｚｏｌｅ ,81,3,4 ｔｈｉａｄｉａｚｏｌｅ9 10ａｎｄｔｈｅｉｒｒｅｌａｔｅｄｃｏ…     

Synthesis of 5-Amino-4-(4-aryl-2-thiazolyl)-2,3-Dihydro-2-Pyrrolones

A method was developed for preparation of 5-amino-4-(4-aryl-2-thiazolyl)-2,3-dihydro-2-pyrrolones by alkylation of 4-aryl-2-thiazolylacetonitriles by N-substituted chloroacetamides in the presence of K₂CO₃. In 1-(1-naphthyl)-substituted pyrrolones atropoisomerism was observed.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 2, 2005, pp. 266–269.Original Russian Text Copyright © 2005 by Resnyanskaya, Tverdokhlebov, Tolmachev, Volovenko.     

微波辐射下一步合成3-氨基-4-氰基-1-芳基-5,6,7,8-四氢异苯并吡喃

亚环己基马来腈与芳醛在哌啶催化下,经微波辐射一步合成3-氨基-4-氰基-1-芳基-5,6,7,8-四氢异苯并吡喃,反应7～11min,产率57%～94%.     

Reactions of Ethyl 2-Amino-5-(2-aryl-2-oxoethylidene)- 4-oxo-4,5-dihydrofuran-3-carboxylates and 2-Amino-5-(2-aryl- 2-oxoethylidene)-4-oxo-4,5-dihydrofuran-3-carbonitriles with Alcohols

Ethyl 2-amino-5-(2-aryl-2-oxoethylidene)-4-oxo-1H-4,5-dihydrofuran-3-carboxylates and 2-amino- 5-(2-aryl-2-oxoethylidene)-4-oxo-1H-4,5-dihydrofuran-3-carbonitriles reacted with alcohols in the presence of a catalytic amount of concentrated aqueous HCl to give the corresponding 5-alkoxy-2-amino-5-(2-aryl-2- oxoethyl)-4-oxo-1H-4,5-dihydrofuran-3-carboxylic acid derivatives. A probable reaction mechanism was proposed on the basis B3LYP/6-311G(d) quantum chemical calculations.     

Synthesis and structure of 3-allenyl-4-aryl-7,7-dimethyl-5-oxo-2-thioxo-1,2,3,4,5,6,7,8-octahydroquinoline-3-carbonitriles

3-Allenyl-4-aryl-7,7-dimethyl-5-oxo-2-thioxo-1,2,3,4,5,6,7,8-octahydroquinoline-3-carbonitriles were synthesized via [3,3]-sigmatropic rearrangement of 4-aryl-7,7-dimethyl-5-oxo-2-(prop-2-yn-1-ylsulfanyl)-1,4,5,6,7,8-hexahydroquinoline-3-carbonitriles. The structure of 3-allenyl-7,7-dimethyl-4-(2-nitrophenyl)-5-oxo-2-thioxo-1,2,3,4,5,6,7,8-octahydroquinolin-3-carbonitrile was determined by X-ray analysis.     

Microwave-Assisted One-Pot Synthesis of 3-Amino-1-aryl-8-bromo-2,4-dicyano-9H-fluorenes in Water

A series of novel 3-amino-1-aryl-8-bromo -2,4-dicyano-9H-fluorenes derivatives were prepared using arylaldehyde, 4-bromo-indanone, malononitrile, and sodium hydroxide as the reactants in water via one-pot synthesis under microwave irradiation. A green and efficient method was successfully developed via microwave irradiation. The method possesses several advantages, such as environmental friendliness, shorter reaction time, and simple workup procedure.      

Efficient and Facile Synthesis of 3-Amino-1-aryl-9H-fluorene-2,4-dicarbonitrile Under Solvent-Free Conditions

A versatile and efficient route to 3-amino-1-aryl-9H-fluorene-2,4-dicarbonitrile via multicomponent reactions of 1-indanone, aromatic aldehydes, and malononitrile under solvent-free conditions using NaOH as the catalyst is described. This method provides several advantages over alternative procedures such as mild, solvent-free conditions at ambient temperature and direct isolation of the products in good yields.