Five-membered 2,3-dioxoheterocycles: LXVII. Pyrroledione-pyrroledion recyclization of isopropyl 2-(1-aryl-4,5-dioxo-2-phenyl-4,5-dihydro-1H-pyrrol-3-yl)-2-oxoacetates under the action of arylamines. Crystal and molecular structure of (z)-isopropyl 2-hydroxy-4,5-dioxo-1-phenyl-3-[phenyl(phenylamino)-methylene]pyrrolidine-2-carboxylate

Reactions of isopropyl 2-(1-aryl-4,5-dioxo-2-phenyl-4,5-dihydro-1H-pyrrol-3-yl)-2-oxoacetates with aromatic amines involve a pyrroledione-pyrroledione recyclization to form isopropyl 1-aryl-2-hydroxy-4,5-dioxo-3-[phenyl(arylamino)methylene]pyrrolidine-2-carboxylates. The crystal and molecular structure of (Z)-isopropyl 2-hydroxy-4,5-dioxo-1-phenyl-3-[phenyl(phenylamino)methylene]pyrrolidine-2-carboxylate was proved by XRD analysis.     

3-溴-1-(3-氯-2-吡啶基)-1H-吡唑-5-甲酸的合成

以2,3-二氯吡啶为起始原料,通过水合肼亲核取代、马来酸二乙酯环合制得2-(3-氯-2-吡啶基)-5-氧-3-吡唑烷甲酸乙酯(5);5经苯磺酰氯酯化、溴化氢溴化制得3-溴-1-(3-氯-2-吡啶基)-4,5-二氢-1H-吡唑-5-甲酸乙酯(7);7经脱氢、水解合成了用于制备氯虫酰胺的关键中间体--3-溴-1-(3-氯-2-吡啶基)-1H-吡唑-5-甲酸,总收率39.5%,其结构经~1H NMR和MS确证.     

Five-membered 2,3-dioxo heterocycles: LXXII. Recyclization of isopropyl 2-(1-aryl-4,5-dioxo-2-phenyl-4,5-dihydro-1H-pyrrol-3-yl)-2-oxoacetates by the action of aliphatic amines

Reactions of isopropyl 2-(1-aryl-4,5-dioxo-2-phenyl-4,5-dihydro-1H-pyrrol-3-yl)-2-oxoacetates with alkylamines involve pyrroledione-pyrroledione recyclization with formation of isopropyl 1-aryl-2-hydroxy-4,5-dioxo-3-[phenyl(alkylamino)methylidene]pyrrolidine-2-carboxylates.     

Synthesis of 1-alkyl-2,3-dihydro-2-(4-pyridinyl)-1H-isoindoles as potential selective serotonin reuptake inhibitors

Two 2,3-dihydro-2-(4-pyridinyl)-1H-isoindoles 2a,b have been synthesized by the reaction of isoindoline with 4-chloropyridines. In addition, a number of 1-alkyl-2,3-dihydro-2-(4-pyridinyl)-1H-isoindoles 2c-h were obtained from 2-(4-pyridinyl)phthalimide (5). The addition of alkyl Grignard reagents to 5 gave 1-alkylhydroxyisoindolones 6a-f which, in two cases 6a,b , were dehydrated and subjected to three separate reductions to give targets 2c,d . In three cases, the intermediate hydroxyisoindolones 6c-e were reduced in one step to the target compounds 2c-g with lithium aluminum hydride-aluminum chloride. When 6f , the product of the addition of phenyl Grignard to 5 , was subjected to these conditions, a hydroxyisoindoline 7 was obtained which was further reduced to 2h with triethylsilane-trifluoroacetic acid. The lithium aluminum hydride-aluminum chloride conditions were successfully applied to the synthesis of a 1-benzyl-4-piperidine derivative 21.     

Reactions of 2-Amino-4-methyl-6-(2-pyridyl)- and 2-Amino-4-methyl-6-phenyl-7,8-dihydroindazolo[4,5-d]thiazoles with Aldehydes

The reaction of 2-amino-4-methyl-6-(2-pyridyl)-7,8-dihydroindazolo[4,5-d]thiazole, obtained by treating 3-methyl-4-oxo-1-(2-pyridyl)-4,5,6,7-tetrahydroindazole with pyridinium bromide perbromide and then with thiourea, and 2-amino-4-methyl-6-phenyl-7,8-dihydroindazolo[4,5-d]thiazole with 4-bromo-, 4-fluoro-, 4-dimethylamino-, 4-methoxy-, 3,4-dimethoxy-, and 3,4-methylenedioxybenzaldehydes, furfural, pyridinecarbaldehyde, and thiophenecarbaldehyde gave the corresponding Schiff bases. The products of the condensation of these aminothiazoles with cinnamaldehyde, 1-(2-pyridyl)- and 4-chloro-1-(2,4-difluorophenyl)-5-formyl-3-methyl-6,7-dihydroindazoles, 2-formyl-dimedone, and 2-formyl-1,3-indanedione were also obtained.     

Synthesis of pyrido[1,2-a]pyrimido[4,5-d]pyrimidin-5-ones. Cyclization reaction of 4-[(3-hydroxy-2-pyridyl)amino]-2-phenyl-5-pyrimidinecarboxylic acid with acetic anhydride

Treatment of 4-[(3-hydroxy-2-pyridyl)amino]-2-phenyl-5-pyrimidinecarboxylic acid (X) with acetic anhydride under refluxing conditions afforded 10-hydroxy-2-phenyl-5H-pyrido[1,2-a]-pyrimido[4,5-d]pyrimidin-5-one acetate (IX). The intermediate X was prepared from 4-chloro-2-phenyl-5-pyrimidinecarboxylic acid ethyl ester (V). The reaction of V with the sodium salt of 2-amino-3-hydroxypyridine at room temperature gave 4-(2-amino-3-pyridyloxy)-2-phenyl-5-pyrimidinecarboxylic acid ethyl ester (VI). Treatment of VI with a hot aqueous sodium hydroxide solution and subsequent acidification gave X. Involvement of 4-[(3-hydroxy-2-pyridyl)amino]-2-phenyl-5-pyrimidinecaroboxylic acid ethyl ester (VIII) (Smiles rearrangement product) as an intermediate in the above alkaline hydrolysis reaction of VI to X was demonstrated by the isolation of VIII and its subsequent conversion into X under alkaline hydrolysis conditions. Acetylation of VIII with acetic anhydride in pyridine solution gave 4-[(3-hydroxy-2-pyridyl)amino]-2-phenyl-5-pyrimidinecarboxylic acid ethyl ester acetate (XI), which afforded IX on fusion at 220°. This alternative synthesis of IX from XI supported the structural assignment of IX. Fusion of VI gave 10-hydroxy-2-phenyl-5H-pyrido[1,2-a]pyrimido]4,5-d]pyrimidin-5-one (VII). The latter was also obtained when VIII was fused at 210°. Acetylation of VII with acetic anhydride afforded IX.     

Reactions of 2-phenyl-4,4-bis(trifluoromethyl)-4,5-dihydro-1,3,2-benzodioxaphosphepin-5-one with phenanthrenequinone and dibenzoyl

Reactions of 2-phenyl-4,4-bis(trifluoromethyl)-4,5-dihydro-1,3,2-benzodioxaphosphepin-5-one with 9,10-phenanthrenequinone and dibenzoyl gave hydrolytically unstable spirophosphoranes with five- and seven-membered rings, 2-phenyl-4,4-bis(trifluoromethyl)-4,5-dihydrospiro[[1,3,2]benzodioxaphosphepine-2,2′-phenanthro[9,10-d][1,3,2]dioxaphosphol]-5-one and 2,4′,5′-triphenyl-4,4-bis(trifluoromethyl)-4,5-dihydrospiro[[1,3,2]benzodioxaphosphepine-2,2′-[1,3,2]dioxaphosphol]-5-one. The structure of the first of these was proved by X-ray analysis.     

5-[5-(3-吡啶)-2H-四唑亚甲基]-2-芳酰氨基-1,3,4-噻二唑的合成

本文首先用5-(3-吡啶)-2H-四唑乙酰基酰肼与芳酰基异硫氰酸盐反应制备成化合物1-[5-(3-吡啶)-2H-四唑乙酰基]-4-芳酰氨基硫脲化合物1a～j, 然后用冰醋酸回流处理1a～j得到一系列化合物5-[5-(3-吡啶)-2H-四唑亚甲基]-2-芳酰氨基-1,3,4-噻二唑2a～j . 化合物1a～b在强碱介质中首先发生降解, 然后进行环化反应 .     

Thermolysis of hexasubstituted-4,5-dihydro-3H-pyrazoles: Synthesis of 1-alkoxy- and 1-acetoxy-1,2,2,3,3-pentasubstituted-cyclopropanes

A series of 5-alkoxy- and 5-acetoxy-4,4-dimethyl-3,3,5-trisubstituted-4,5-dihydro-3H-pyrazoles 2a-f (hexasubstituted pyrazolines) was synthesized by oxidation of the corresponding 3,4-dihydro-2H-pyrazoles with lead tetraacetate in the appropriate solvents. The 5-acetoxy compounds were produced when the oxidations were carried out in methylene chloride. Oxidation with lead tetraacetate in dry alcoholic solvents resulted in the formation of the 5-alkoxy derivatives as the major products. Thermolysis of the hexasubstituted-4,5-dihydro-3H-pyrazoles 2a-f in cyclohexane or as the melt at high temperature yielded the 1-alkoxy- and 1-acetoxy-1,2,2,3,3-pentasubstituted cyclopropanes 3a-f in good yields. Trace amounts of alkene products were formed in several reactions. No products attributable to cycloreversion pathways were detected. The product distributions were consistent with extrusion of nitrogen gas from 2a-f to yield the singlet 1,3-diradical, closure of which resulted in cyclopropane formation with partial retention of stereochemistry.     

Efficient synthesis of 3,4- and 4,5-dihydroxy-2-amino-cyclohexanecarboxylic acid enantiomers

An efficient method for the synthesis of (1S,2R,4R,5S)- and (1R,2R,4R,5S)-2-amino-4,5-dihydroxycyclohexanecarboxylic acids (?)-6 and (?)-9 and (1R,2R,3S,4R)- and (1S,2R,3S,4R)-2-amino-3,4-dihydroxycyclohexanecarboxylic acids (?)-15 and (?)-18 was developed by using the OsO₄-catalyzed oxidation of Boc-protected (1S,2R)-2-aminocyclohex-4-enecarboxylic acid (+)-2 and (1R,2S)-2-aminocyclohex-3-enecarboxylic acid (+)-11. Good yields were obtained. The stereochemistry of the synthesized compounds was proven by NMR spectroscopy.     

Synthesis and Alkylation of Piperidinium 4,5-trans-3-Cyano-6-hydroxy-4-(2-iodophenyl)-6-methyl-5-(2-methylphenyl)carbamoyl-1,4,5,6-tetrahydropyridine-2-thiolate. Molecular and Crystal Structure of 3-(2-Iodophenyl)-2-(4-phenyl-2-thiazolyl)acrylonitrile

The reaction of o-iodobenzaldehyde, cyanothioacetamide, and N-acetoacetyl-o-toluidine in the presence of piperidine gave piperidinium 4,5-trans-3-cyano-6-hydroxy-4-(2-iodophenyl)-6-methyl-5-(2-methylphenyl)carbamoyl-1,4,5,6-tetrahydropyridine-2-thiolate used in the synthesis of substituted 4,5-trans-2-alkylthiotetrahydropyridines and 2-(2-thiazolyl)acrylonitriles. The structure of 3-(2-iodophenyl)-2-(4-phenyl-2-thiazolyl)acrylonitrile was studied using X-ray diffraction structural analysis.     

Eine überraschende Ringerweiterung von 3-(Dimethylamino)-2,2-dimethyl-2H-azirin zu 4,5-Dihydropyridin-2(3H)-on-Derivaten

An Unexpected Ring Enlargement of 3-(Dimethylamino)-2,2-dimethyl-2H-azirine to 4,5-Dihydropyridin-2(3H)-one Derivatives The reaction of 3-(dimethylamino)-2,2-dimethyl-2H-azirine ( 1a ) and 4,4-disubstituted 2-(trifluoromethyl)-1,3-oxazol-5(4H)-ones 7 in MeCN at 70° afforded 5-(dimethylamino)-3,6-dihydropyrazin-2(1H)-ones 10 (Scheme 4), whereas no reaction could be observed between 1a and 2-allyl-4-phenyl-2-(trifluoromethyl)-1,3-oxazol-5(2H)-one ( 8a ) or 4,4-dibenzyl-2-phenyl-1,3-oxazol-5(4H)-one ( 9 ). The formation of 10 is rationalized by a mechanism via nucleophilic attack of 1a onto 7 . The failure of a reaction with 9 shows that only activated 1,3-oxazol-5(4H)-ones bearing electron-withdrawing substituents do react as electrophiles with 1a . The amino-azirine 1a and 2,4-disubstituted 1,3-oxazol-5(4H)-ones 2b – e in refluxing MeCN undergo a novel ring enlargement to 4,5-dihydropyridin-2(3H)-ones 11 (Scheme 5). Several side products were observed in these reactions. Two different reaction mechanisms for the formation of 11 are proposed: either 1a undergoes a nucleophilic addition onto the open-chain ketene tautomer of 2 (Scheme 6), or 2 reacts as CH-acidic compound (Scheme 7).     

4,5-Dihydropyrazolo[3,4-f]quinazolines

By reaction of 6-dimethylamino-5-oxo-2-phenyl-5,6,7,8-tetrahydroquinazoline with hydrazine, phenylhydrazine, 4-bromo-, 4-chlorophenylhydrazines, and also reaction of 6-dimethylaminomethylene-5-oxo-2-(4-pyridyl)-5,6,7,8-tetrahydroquinazoline with hydrazine, 4-methoxy- and 2-carboxyphenylhydrazines, we have obtained the corresponding 7-phenyl(4-pyridyl)-substituted 1H(2H)- or 1-aryl-4,5-dihydropyrazolo[3,4-f]quinazolines. Methylation of 7-phenyl-4,5-dihydro-1(2H)-pyrazolo[3,4-f]quinazoline by methyl iodide led to its 2-methyl derivative.     

5-Aryl-1-[pyrimidin-2(4)-yl]-3-phenyl-4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrazoles. Synthesis from substituted 2(4)-hydrazinopyrimidines and fragmentation under positive electrospray ionization

Reaction of substituted 2(4)-hydrazinopyrimidines with 3-aryl-1-phenyl-2-propen-1-ones in the presence of a base results prevailingly in 5-aryl-1-[pyrimidin-2(4)-yl]-3-phenyl-4,5-dihydro-1H-pyrazoles. The fragmentation path of these compounds under positive electrospray ionization consists in simultaneous decomposition of their heterocyclic fragments.     

Investigations in the benzazole and naphthazole series

1-[4(7)-Benzimidazolyl]-5-phenyl- and 1-[4(7)-benzimidazolyl]-5-(2-benzimidazolyl)formazans, which are isomers of the previously obtained 1-(2-benzimidazolyl)-5-phenyl- and 1,5-di(2-benzimidazolyl)formazans, were synthesized. Structural problems (tautomerism and hydrogen bonding) of the new formazans are discussed.See [1] for communication XXXV.Translated from Khimiya Geterotsiklicheskikh Soedinenii,,No. 8, pp. 1138–1140, August, 1972.     

5-[5-(3-吡啶)-2H-四唑亚甲基]-2-芳酰氨基-1,3,4-噻二唑的合成

正如前文报道,l,3,4—噻二唑类杂环之所以有除草,植物生长调节,驱虫以及消炎等多种生物活性,无疑起因于噻唑母核。尽管母核上取代基不起主导作用,但它作为辅助基,在改善分子溶解性以及药效方面所产生的影响是不能忽略的。因而深入研究各种生物活性基团导入噻二唑环母核以制得多结构单元聚集于同一分子中的噻二唑新衍生物,对于开发多功能新药具有一定的理论意义和实际价值。     

Microwave Assisted Synthesis of 5-[4-(3-Phenyl-4,5-dihydro-1H-pyrazol-5-yl)phenyl]-1H-tetrazole Derivatives and Their Antimicrobial Activity

Russian Journal of General Chemistry - In the present study, we report the synthesis of 5-[4-(3-phenyl-4,5-dihydro-1H-pyrazol-5-yl)phenyl]-1H-tetrazole derivatives by the Michael addition of...     

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.     

Amidrazones 11. Rearrangement of 1-allyl-substituted-4,5-dihydro-1-methyl-1H-pyrazolium bromides

1-Methyl-2-(2-propenyl)-3-pyrazolidinimine ( 5 ) was obtained by treatment of 3-amino-4,5-dihydro-1-methyl- 1-(2-propenyl)-1H-pyrazolium bromide ( 4 ) with ethanolic sodium ethoxide. Similar treatment of the analogous 2-(2-butenyl) and 2-(3-phenyl-2-propenyl)-substituted salts 12 and 15 gave 1-methyl-2-(1-methyl-2-propenyl)-3- pyrazolidinimine ( 13 ) and 1-methyl-2-(1-phenyl-1-propenyl)-3-pyrazolidinimine ( 16 ) respectively.     

1,1-二(2-苯并咪唑基)-2-苯基乙烯衍生物荧光受体的合成与阳离子识别

合成了3种新型1,1-二(2-苯并咪唑基)-2-苯基乙烯衍生物——1,1-二(2-苯并咪唑基)-2(4-氰基苯基)乙烯(1)、1,1-二(2-苯并咪唑基)-2(4-甲氧羰基苯基)乙烯(2)和1,1-二(2-苯并咪唑基)-4-苯基-1,3-丁二烯(3),通过核磁共振氢谱和碳谱(1H、13C NMR)、质谱(MS)对它们进行了结构表征。用紫外可见吸收光谱(UV-V is)和荧光发射光谱测定了该阳离子受体与不同金属离子(Zn2 、Cd2 、Hg2 和Cu2 )的络合选择性。结果表明:该荧光受体对Zn2 、Cd2 、Hg2 和Cu2 均具有较高的选择性和荧光响应。