Synthesis of polyheterocyclic compounds derived from 6-amino- 4-aryl-2-r-4h-furo[2,3-<Emphasis Type="Italic">b</Emphasis>]pyran-5-carbonitriles

Syntheses were developed for 4-aryl-6-ethoxy-2-R-furo[2,3-b]pyridine-5-carbonitriles and ethyl esters of 5-amino-4-aryl-7-methyl-2-R-1,9-dioxa-8-azacyclopenta[b]naphthalene-6-carboxylic acids based on the reaction of 6-amino-4-aryl-2-R-4H-furo[2,3-b]pyran-5-carbonitriles with ethyl acetoacetate and nucleophilic recyclization. The mechanisms of these reactions are considered.     

Synthesis of heterocycles. Part VI. Synthesis and antimicrobial activity of some 4-amino-5-aryl-1,2,4-triazole-3-thiones and their derivatives

4-Amino-5-aryi-1,2,4-triazole-3-thiones I react with acid chlorides to yield 4-acylamino-5-aryl-1,2,4-triazole-3-thiones II. Compounds I also react with methylene iodide, chloroacetonitrile and methyl bromoacetate to give bis-(4-amino-5-aryl-1,2,4-triazol-3-ylthio)methanes III, 4-amino-5-aryl-3-cyanomethylthio-1,2,4-triazoles IV and 4-amino-5-aryl-3-carbomethoxymethylthio-1,2,4-triazoles V, respectively. Compounds V react with hydrazine hydrate to give the corresponding acid hydrazides VI which in turn condenses with acid chlorides and aldehydes to afford respectively 1-[(4-amino-5-aryl-1,2,4-triazol-3-ylthio)acetyl]-2-aroylhydrazines VII and aryl methylene (4-amino-5-aryl-1,2,4-triazol-3-ylthio)acethydrazones VIII. The antimicrobial activities of the above compounds were screened against different strains of bacteria and fungi.     

Potassium phthalimide promoted green multicomponent tandem synthesis of 2-amino-4H-chromenes and 6-amino-4H-pyran-3-carboxylates

A one-pot efficient, green, practical, and environmentally friendly multicomponent synthesis of 5-oxo-4-aryl-5,6,7,8-tetrahydro-4H-chromenes, ethyl-6-amino-4-aryl-5-cyano-2-methyl-4H-pyran-3-carboxylates as well as 2-amino-4-aryl-7-hydroxy-4H-chromene-3-carbonitriles via tandem the Knoevenagel-cyclocondensation has been described in the presence of a green, low-cost, mild, efficient, and commercially available potassium phthalimide as the organocatalyst. This technique is a safe and ecofriendly approach to the synthesis of different 4H-chromens and 4H-pyrans that offers many merits including short reaction times, high yields, straightforward work-up, and no use of hazardous organic solvents.     

微波辐射一步法合成吡喃和吡喃[2, 3-c]吡唑衍生物

芳醛、丙二腈与5,5-二甲基-1,3-环己二酮或3-甲基-1-苯基-2-吡唑啉-5-酮在乙醇溶剂中用哌啶作催化剂,经微波辐射一步合成了2-氨基-3-氰基-4-芳基-7,7-二甲基-5-氧代-5,6,7,8-四氢苯并吡喃和6-氨基-5-氰基-4-芳基-1,4-二氢吡喃[2,3-c]吡唑,反应在2～12min内完成,产率53%～91%。     

Synthesis of 1,4,5-trisubstituted-1,2,3-triazoles via coupling reaction of diaminomaleonitrile with aromatic diazonium salts

A mild procedure for the preparation of 2-(5-amino-1-aryl-1H-1,2,3-triazol-4-yl)-2-iminoacetonitriles and 2-(5-amino-1-aryl-1H-1,2,3-triazol-4-yl)-2-oxoacetonitriles was achieved by the reaction of diaminomaleonitrile and phenyl/substituted phenyl diazonium chlorides. 4-Nitrophenyl diazonium chloride afforded 2-amino-3-(3-(4-nitrophenyl)triaz-1-en-1-yl)maleonitrile. Triazole iminoacetonitrile and maleonitrile derivatives were reacted further with excess acetone and benzaldehyde with a catalytic amount of 1,8-diazabicyclo[5.4.0]undec-7-ene to yield 5-(5-imino-2,2-dimethyl-2,5-dihydrooxazol-4-yl)-3-aryl-3H-1,2,3-triazol-4-amine and (E)-N-benzylidene-5-(5-imino-2-aryl-2,5-dihydrooxazol-4-yl)-3-aryl-3H-1,2,3-triazol-4-amine, respectively. Two competitive reactions, i.e., nucleophilic substitution and nucleophilic addition, were observed when triazole oxoacetonitrile and maleonitrile derivatives were reacted with hydroxylamine hydrochloride in the presence of sodium acetate.     

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.     

2-Acyl(aroyl)-1,1,3,3-tetracyanopropenides: VI. Reaction with hydrogen halides

Reactions of 2-aroyl-1,1,3,3-tetracyanopropenides with hydrogen halides in solvents of low dielectric permittivity result in the formation of 6-amino-2-aroyl-2-halopyridine-3,5-dicarbonitriles. 2-Acyl-1,1,3,3-tetracyanopropenides under similar conditions afford 2-(2-alkylidene-5-amino-4-cyano-2,3-dihydrofuran-3-ylidene)propanedinitriles. In solvents of high dielectric permittivity the result of the reaction depends on the nature of the hydrogen halide and the acyl(aroyl) substituent: With HCl and HBr 2-aroyl-1,1,3,3-tetracyanopropenides form 2-(5-amino-2-aryl-2-halo-4-cyano-2,3-dihydrofuran-3-ylidene)-propanedinitriles, and 2-acyl-1,1,3,3-tetracyanopropenides give 2-(2-alkylidene-5-amino-4-cyano-2,3-dihydrofuran-3-ylidene)propanedinitriles; with HI depending on the reaction conditions and the structure of the acyl substituent 2-(5-amino-2-aryl-4-cyano-2,3-dihydrofuran-3-ylidene)propanedinitriles, 2-(5-amino-4-cyano-2,3-dihydrofuran-3-ylidene) propane-dinitrile, 2-amino-4-(dimethoxybenzyl)-6-iodo-5-cyanonicotinamide, 4-amino-6-iodo-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-7-carbonitrile, or 4-amino-6-iodo-3-oxo-1-ethylidene-1,3-dihydrofuro[3,4-c]pyridine-7-carbonitrile are obtained.     

Reactions of 1-aryl-2-bromo-3,4,4-trichlorobut-3-en-1-ones with some nucleophilic reagents

Reactions of 2-bromo-1-phenyl- and 2-bromo-1-(4-methylphenyl)-3,4,4-trichlorobut-3-en-1-ones with morpholine and diethylamine are accompanied by prototropic allylic rearrangement, leading to 3-amino-1-aryl-2-bromo-4,4-dichlorobut-2-en-1-ones as mixtures of E and Z isomers. The title compounds react with hydrazine, hydroxylamine, and thiourea to give the corresponding 5-aroyl-4-methoxypyrazoles, 3-aryl-5-hydroxyiminomethyl-4-methoxyisoxazoles, and 2-amino-4-aryl-5-trichlorovinylthiazoles.     

Palladium-catalyzed reaction of methyl 5-amino-4-chloro-2-methylthiopyrrolo[2,3-<Emphasis Type="Italic">d</Emphasis>]-pyrimidine-6-carboxylate with arylboronic acids. Synthesis of 1,3,4,6-tetraazadibenzo[<Emphasis Type="Italic">cd,f</Emphasis>]-azulene heterocyclic system

Densely substituted methyl 5-amino-4-aryl-7-methyl-2-methylthio-7H-pyrrolo[2,3-d]pyrimidine-6-carboxy- lates were synthesized by the palladium-catalyzed cross-coupling reaction of methyl 5-amino-4-chloro-7-methyl-2-methylthio-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate with arylboronic acids using Pd(OAc)₂/dicyclohexyl(2-biphenyl)phosphine/K₃PO₄ as a catalyst system. Reaction of methyl 5-amino-4-chloro-7-methyl-2-methylthio-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate with 2-formylphenyl- boronic acid led to a novel heterocyclic system – 1,3,4,6-tetraazadibenzo[cd,f]azulene.     

Piperidine-mediated synthesis of thiazolyl chalcones and their derivatives as potent antimicrobial agents

A series of new thiazolyl chalcones, 1-[2-amino-4-methyl-1,3-thiazol-5-yl]-3-aryl-prop-2-en-1-one were prepared by piperidine mediated Claisen-Schmidt condensation of thiazolyl ketone with aromatic aldehyde. These chalcones on cyclisation gave 2-amino-6-(2-amino-4-methyl-1,3-thiazol-5-yl)-4-aryl-4H-pyridine-3-carbonitrile and 2-amino-6-(2-amino-4-methyl-1,3-thiazol-5-yl)-4-aryl-4H-pyran-3-carbonitrile. The result showed that the compounds exhibited marked potency as antimicrobial agents.     

稠杂环化合物的研究(Ⅳ)——5-醛胺基-1-芳基-1,2,3-连三唑[2,3-d]嘧啶-4-酮类衍生物的合成及抗菌性能

我们已报道了1-芳基-4-乙氧羰基-5-氨基-1,2,3-连三唑类衍生物(1)的合成及抗菌活性,为研究药物构效关系,我们利用1的酰肼3同甲酸反应,制得了尚未报道的5-醛胺基-1-芳基-1,2,3-连三唑[2,3-d]嘧啶-4-酮(4_(a-c))及5-氨基-6-羟基-7H-1-(间硝基)苯基-1,2,3-连三唑[2,3-d]嘧啶-4-酮(5_d).并观察了它们对枯草杆菌,金黄色葡萄球菌等繁殖的抑制作用。     

Synthesis of heterocycles based on arylation products of unsaturated compounds: XVII. Arylation of 2-acetylfuran and synthesis of 3-R-6-(5-aryl-2-furyl)-7<Emphasis Type="Italic">H</Emphasis>-[1,2,4]triazolo[3,4-<Emphasis Type="Italic">b</Emphasis>][1,3,4]thiadiazines

Reaction of 2-acetylfuran with arenediazonium chlorides under Meerwein reaction conditions led to the formation of 5-aryl-2-acetylfurans. The bromination of these compounds gave 2-bromo-1-(5-aryl-2-furyl)-ethanones that reacted with 4-amino-4H-5-R-1,2,4-triazole-3-thiols to form 3-R-6-(5-aryl-2-furyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines.     

Reaction of 4-thioxo-1,3-benzothiazines with thiocarbohydrazine: Synthesis and reactivity of 1,3,4-triazolo[3,2-c]quinazoline derivatives

2-Aryl-4-thioxo-1,3-benzothiazines react with thiocarbohydrazide to give the new mesoionic compounds an-hydro 1-amino-5-aryl-2-mercapto-1,3,4-triazolo[3,2-c]quinazolin-4-ium hydroxides. These compounds react with methyl iodide, aldehydes and phenacyl bromides to give 1-amino-5-aryl-2-methylthio-1,3,4-triazolo-[3,2-c]quinazolin-4-ium iodides, 4-arylidenamino-3-(o-aroylamino)phenyl-1H-1,2,4-triazolin-5-thiones and 3-(o-aroylamino)phenyl-6-aryl-7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines, respectively. These latter compounds by sequential treatment with methyl trifluoromethanesulphonate and triethylamine lead to 3-(o-aroylamino)-phenyl-6-aryl-1-methyl-7-mercapto-1H-pyrazolo[5,1-c]-1,2,4-triazoles.     

Synthesis of aminonicotinonitriles and diaminopyridines through base-catalyzed ring transformation of 2H-pyran-2-ones

An efficient and convenient synthesis of 2-amino-6-aryl-4-methylsulfanylnicotinonitriles (2), 2-amino-6-aryl-4-substituted-aminonicotinonitriles (4), and 2-amino-6-aryl-4-substituted-aminopyridines (6) has been delineated and illustrated through base-catalyzed ring transformation of 6-aryl-3-cyano-4-methylsulfanyl/substituted-amino-2H-pyran-2-ones (1, 3, and 5) with cyanamide and ammonium carbonate separately.     

Synthesis of 6-aryl-1,3-dimethyl-6,7-dihydro-6-azalumazin-7-(6H)ones and their conversion into 2-aryl-1,2,4-triazine-3,5-(2H,4H)odiones. A new synthesis of 1-aryl-6-azauracils

Treatment of 6-amino-5-arylazo-1,3-dimethyluracils with urea or N,N′-carbonyldiimidazole gave the respective 6-aryl-1,3-dimethyl-6,7-dihydro-6-azalumazin-7-(6H)ones, which were hydrolyzed with alkali to afford 2-aryl-2,3,4,5-tetrahydro-3,5-dioxo-1,2,4-triazine-6-carboxylic acids (1-aryl-6-azauracil-5-carboxylic acids). Thermal decomposition of these carboxylic acids gave the corresponding 2-aryl-1,2,4-triazine-3,5-(2H,4H)diones (1-aryl-6-azauracils). Methylation of the latter with methyl iodide gave the corresponding 2-aryl-4-methyl-1,2,4-triazine-3,5-(2H,4H)diones (1-aryl-3-methyl-6-azauracils).     

A novel and efficient synthesis of pyrazolo[3,4-d]pyrimidine derivatives and the study of their anti-bacterial activity

In this work 4-amino-6-aryl-2-phenyl pyrimidine-5-carbonitrile derivatives were synthesized through a one-pot,three-component reaction of an aldehyde,malononitrile and benzamidine hydrochloride,in the presence of magnetic nano Fe₃O₄ particles as a catalyst under solvent-free conditions.3-Amino-6-aryl- 2-phenylpyrazolo[3,4-d]pyrimidine derivatives were prepared through an efficient and environmentally friendly reaction between 4-amino-6-aryl-2-phenylpyrimidine-5-carbonitrile derivatives and hydrazine hydrate and their antibacterial activity has been evaluated.     

Research on nitrogen and sulfur-containing heterocycles

2-Mercapto-3-amino-5-chloropyridine reacts with phenacyl halides to yield 2-phenacylmercapto-3-amino-5-chloropyridines and 2-aryl-7-chloro-3H-pyrido[2, 3-b][1, 4]thiazines.For part V, See [11].     

Synthesis and chemical properties of 8-aryl-7-acyl-1-6-dimethyl-6-hydroxy-4-cyano-5,6,7,8-tetrahydro-3(2H)-isoquinolinones and isoquinolinethiones

8-Aryl-7-acetyl-1, 6-dimethyl-6-hydroxy-4-cyano-5, 6, 7, 8-tetrahydro-3(2H)-isoquinolinones and -isoquinolinethiones and their sodium salts were obtained by the reaction of cyanoacetamide and cyanothioacetamide with 3-aryl-2, 4-diacetyl-5-methyl-5-hydroxycyclohexanonesinbasicrnedium. 8-Aryl-7-acetyl-6-methoxycarbonyl-1, 6-dimethyl-4-cyano-5, 6, 7, 8-tetrahydro-3(2H)-isoquinolinones were obtained by the reaction of acetyl chloride and the above isoquinolinone sodium salts. The reaction of iodoacetamide and the above isoquinolinethione sodium salts yielded 8-aryl-7-acetyl-3-carbamoylmethylthio-1, 6-dimethyl-4-cyano-5, 6, 7, 8-tetra-hydroisoquinolines, which were cyclized into 1-amino-6-aryl-7-acetyl-2-carbamoyl-5, 8-dimethyl-8-hydroxy-6, 7, 8, 9-tetrahydrothiophene[2,3-c]isoquinolines in basic medium.     

Exploratory chemistry of 3-aroylformamido-4-aryl-1,2,5-thiadiazoles

Apart from the previous report, the reaction of 3-(4-nitrobenzoylformamido)-4-(4-nitrophenyl)-1,2,5-thiadiazole ( 2a ) with m-chloroperbenzoic acid in chloroform at room temperature did not proceed, whereas at reflux temperature the same reaction gave 4-nitrobenzoic acid ( 5 ) (86%) and a minute amount of a mixture of 4-nitrobenzoylformamide ( 6 ) and 3-amino-4-(4-nitrophenyl)-1,2,5-thiadiazole ( 7a ). On the other hand the same reaction in a mixture of ethanol and chloroform (1:4) at room temperature gave 3-ethoxycarbamoyl-4-(4-nitrophenyl)-1,2,5-thiadiazole ( 8a ) (24%) as an isolable product. When 3-aroylformamido-4-aryl-1,2,5-thiadiazoles 2 in tetrahydrofuran were treated with various alkoxides in the corresponding alcohols at room temperature, 3-amino-4-aryl- 7 , 3-alkoxycarbamoyl-4-aryl- 8 , and 3-aryl-4-(aryl)(hydroxy)acetamido-1,2,5-thiadiazoles 9 were isolated. The ratios of which were dependent on the kind of bases and the solvent employed. Selected compounds 2 were allowed to react with phosphorus pentasulfide in the presence of pyridine at reflux to give 3-aryl-4-arylacetarnido-1,2,5-thiadiazoles 17 (55–64%), which were also produced by the reaction of 2 with either Lawesson's reagent or hydrogen sulfide gas in the presence of pyridine at reflux.     

Compounds in the pyrrolo[3,4-d]pyrimidine series. derivatives with 6-aryl substituents

Methods are described for the synthesis of 6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidines having an aryl substituent in the 6-position. 4-Hydroxy-, 4-amino, 2-amino-4-hydroxy and 2,4-diamino derivatives were obtained. The synthetic route involved the preparation of 1-aryl-4-cyano- or 4-carboalkoxy-3-pyrrolidinones and 1-aryl-4-cyano- or 4-carboalkoxy-3-amino-3-pyrrolines as key intermediates.