2-取代硫醚-5-(5,7-二甲基-1,2,4-三唑并[1,5-a]嘧啶基)-1,3,4-噁二唑/噻二唑类化合物的合成及生物活性

以5-氨基-1H-1,2,4-三唑-3-羧酸乙酯为起始原料, 设计合成了11个新型的2-取代硫醚-5-(5,7-二甲基-1,2,4-三唑并[1,5-a]嘧啶基)-1,3,4-噁二唑类化合物(5)和6个新型的2-取代硫醚-5-(5,7-二甲基-1,2,4-三唑并[1,5-a]嘧啶基)-1,3,4-噻二唑类化合物(8). 通过¹H NMR, MS和元素分析对所合成的化合物进行了结构表征. 初步的生物活性测试结果表明, 所合成的化合物均表现出不同程度的除草及杀菌活性, 其中化合物5k和8f的活性最好, 在50 mg/L浓度下对水稻纹枯病菌的抑制率达90%以上.     

7-取代苯氧基-4,5-二氢-1,2,4-三唑并[4,3-a]喹啉和喹啉-1(2H)-酮衍生物的合成及抗惊厥活性

合成了7-取代苯氧基-4,5-二氢-1,2,4-三唑并[4,3-a]喹啉(3a～3g)和7-取代苯氧基-4,5-二氢-1,2,4-三唑并[4,3-a]喹表明啉-1(2H)-酮(4a～4g)类衍生物. 以最大电惊厥法和戊四唑法测定了抗惊厥活性, 以旋转棒法测定了神经毒性. 结果表明, 化合物7-(4-氟苯氧基)-4,5-二氢-1,2,4-三唑并[4,3-a]喹啉-1(2H)-酮(4c)显示最强的抗惊厥作用和低的神经毒性, 其抗电惊厥ED₅₀为6.8 mg/kg, 神经毒性TD₅₀为88.0 mg/kg, 保护指数PI为12.9, 明显优于对照药苯妥英钠.     

2-甲硫基-7(5)-取代-3-吡唑并[1,5-a]嘧啶甲酸乙酯的区域选择性合成与2D NMR 研究

利用3-甲硫基-4-乙氧羰基-5-氨基-1H-吡唑分别与甲基/芳基烯胺酮反应, 合成了8种新的化合物2-甲硫基-7-取代-3-吡唑并[1,5-a]嘧啶甲酸乙酯(3a～3g)和2-甲硫基-5-甲基-3-吡唑并[1,5-a]嘧啶甲酸乙酯(4a). 化合物的结构均经元素分析, IR, ¹H NMR, MS所证实, 异构体3a和4a的结构进一步由¹³C NMR, HMQC和HMBC确认. 同时, 探讨了区域选择性合成吡唑并[1,5-a]嘧啶类化合物可能的反应机理, 并对部分化合物杀菌活性进行了测试.     

含噁二唑杂环取代的新型三唑并嘧啶衍生物的合成及其生物活性

2-肼羰基亚甲硫基-5,7-二甲基-1,2,4-三唑并[1,5-a]嘧啶与二硫化碳在乙醇溶液中回流制得化合物2-(5-巯基-1,3,4-噁二唑-2-亚甲硫基)-5,7-二甲基-1,2,4-三唑并[1,5-a]嘧啶, 后者在碱性环境中与卤化苄反应得到17种新型双杂环化合物. 对所得化合物结构均经元素分析, ¹H NMR和MS确认. 初步生物活性测试表明这些化合物具有一定的杀菌活性.     

三组分“一锅煮”合成4,5-二氢吡唑并[1,5-a]嘧啶

以芳香醛、5-氨基-1H-吡唑和丙二腈为原料, 三组分“一锅煮”合成4,5-二氢吡唑并[1,5-a]嘧啶类化合物. 所有化合物均经IR, ¹H NMR和元素分析检测. 该法是一种操作简单, 产率较高的方法.     

新型1,2,4-三唑[3,4-b]-1,3,4-噻二嗪的合成及表征

以3-(2-苯基-1,2,3-三唑-4-基)-4-氨基-5-巯基-1,2,4-三唑(1)为原料分别与ω-溴代芳基乙酮、ω-溴代-ω-(1H-1,2,4-三 唑-1-基)芳基乙酮反应, 合成了一系列新的1,2,4-三唑[3,4-b]-1,3,4-噻二嗪类化合物2a～2e和3a～3e. 其结构经IR, ¹H NMR和MS及元素分析确证.     

在离子液体中一步法合成吡唑[5,4-b]-γ-吡喃衍生物

芳醛、丙二腈与4,5-二氢-3-甲基-5-氧代-1-苯基吡唑在离子液体[bmim][BF₄]中反应, 合成了2-氨基-4-芳基-3-氰基-5-甲基-7-苯基吡唑[5,4-b]-γ-吡喃衍生物, 该法快速、高效, 是一种洁净的合成方法. 产物的结构通过红外光谱、核磁共振氢谱和元素分析进行表征.     

含三唑基的新型咪唑[2,1-b]-1,3,4-噻二唑的合成及表征

以2-(2-苯基-1,2,3-三唑-4-基)-5-氨基-1,3,4-噻二唑(1)为原料分别与ω-溴代芳基乙酮、ω-溴代-ω-(1H-1,2,4-三唑-1-基)芳基乙酮反应, 合成了一系列新型咪唑[2,1-b]-1,3,4-噻二唑类化合物2a～2e和3a～3e. 其结构经IR, ¹H NMR和MS及元素分析确证.     

微波辐射下合成5-(2-甲基/三氟甲基-苯并咪唑-1-亚甲基)-3-(苯基/p-取代苯基)-2H-1',2',4'-三唑[3,4-b]-1

分别采用微波辐射法和加热回流的常规方法, 将1-氨基-2-(2-甲基/三氟甲基-苯并咪唑-1-亚甲基)-5-巯基-1,3,4-三唑与α-溴代芳基乙酮3a～3e反应, 合成了一系列未见文献报道的1,2,4-三唑[3,4-b]-1',3',4'-噻二嗪类化合物4a～4e 和5a～5e. 微波辐射法具有反应时间短、产率高、副反应少等优点. 标题化合物经元素分析, IR, ¹H NMR, MS确证结构.     

微波促进下3-(2-苯并呋喃基)-4-氨基-5-巯基-1,2,4-三唑

微波辐射条件下, 首先由2-苯并呋喃甲酰肼依次与二硫化碳和水合肼反应合成3-(2-苯并呋喃基)-4-氨基-5-巯基- 1,2,4-三唑, 进一步在微波辐射条件下由4-氨基-5-巯基-1,2,4-三唑分别与芳甲酸/芳氧基乙酸、α-溴代苯乙酮及芳醛反应以较高产率制得了相应的1,2,4-三唑并[3,4-b]-1,3,4-噻二唑、1,2,4-三唑并[3,4-b]-1,3,4-噻二嗪及4-芳亚甲基亚胺基-5-巯基-1,2,4-三唑. 产物结构经IR, ¹H NMR, MS及元素分析进行了表征.     

A synthesis of 6-functionalized 4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidines

6-Unsubstituted 7-R-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidines (R = H or Me) were synthesized via two pathways: (a) deacylation of the corresponding 5-acetyl Biginelli-like precursors in KOH/H₂O and (b) reduction of the corresponding 1,2,4-triazolo[1,5-a]pyrimidines using LiAlH₄. The products could be easily formylated at position 6, which is promising for the further synthesis of functionalized 6-substituted derivatives of 4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidines. In contrast, 6-acetyl-7-(4-(N,N-dimethylaminophenyl))-5-methyl-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine undergoes a cascade process in KOH/H₂O, leading to the formation of a 4,5,8,9-tetrahydro[1,2,4]triazolo[5,1-b]quinazoline derivative.     

NMR study on the tautomeric equilibria between the hydrazone imine and diazenyl enamine forms in side chained quinoxalines: Solvent effects and temperature dependence

The reaction of 7-chloro-4-ethoxycarbonylmethylene-4,5-dihydro-1,2,4-triazolo[4,3-a]quinoxaline 6 with 4-ethoxycarbonyl-1-methyl-1H-pyrazole-5-diazonium chloride or 4-cyano-1,3-dimethyl-1H-pyrazole-5-diazonium chloride gave 7-chloro-4-[α-(4-ethoxycarbonyl-1-methyl-1H-pyrazol-5-ylhydrazono)-ethoxycarbonylmethyl]-1,2,4-triazolo[4,3-a]quinoxaline 8a or 7-chloro-4-[α-(4-cyano-1,3-dimethyl-1H-pyrazol-5-ylhydrazono)ethoxycarbonylmethyl]-1,2,4-triazolo[4,3-a]quinoxaline 8b , respectively, while the reaction of 7-chloro-4-ethoxycarbonylmethylene-4,5-dihydrotetrazolo[1,5-a]quinoxaline 7 with 4-ethoxycarbonyl-1-methyl-1H-pyrazole-5-diazonium chloride or 4-cyano-1,3-dimethyl-1H-pyrazole-5-diazomum chloride provided 7-chloro-4-[α-(4-ethoxycarbonyl-1-methyl-1H-pyrazol-5-ylhydrazono)ethoxycarbonylmethyl]tetrazolo[1,5-a]quinoxaline 9a or 7-chloro-4-[α-(4-cyano-1,3-dimethyl-1H-pyrazol-5-ylhydrazono)ethoxycarbonylmethyl]tetrazolo[1,5-a]quinoxaline 9b , respectively. Compounds 8a,b and 9a,b showed the tautomeric equilibria between the hydrazone imine C and diazenyl enamine D forms in dimethyl sulfoxide and/or trifluoroacetic acid, and the effects of solvent and temperature on the tautomer ratios of C to D were studied by the nmr measurements in a series of mixed trifluoroacetic acid/dimethyl sulfoxide media (compounds 8a,b and 9a,b ) and at various temperatures (compounds 8a,b ).     

A facile synthesis of enol type acyl cyanides via a 1,3-dipolar cycloaddition reaction and a cyano group migration

The reaction of 7-chlorotetrazolo[1,5-a]quinoxaline 5-oxide 4a or 7-chloro-1,2,4-triazolo[4,3-a]quinoxaline 5-oxide 4b with 2-chloroacrylonitrile gave 7-chloro-4-(2-cyano-2-hydroxyvinyl)tetrazolo[1,5-a]quinoxaline 5a or 7-chloro-4-(2-cyano-2-hydroxyvinyl)-1,2,4-triazolo[4,3-a]quinoxaline 5b , respectively. Alcoholysis of compound 5a or 5b afforded 7-chloro-4-ethoxycarbonylmethylene-4,5-dihydrotetrazolo[1,5-a]quinoxaline 6a or 7-chloro-4-ethoxycarbonylmethylene-4,5-dihydro-1,2,4-triazolo[4,3-a]quinoxaline 6b , respectively. Compounds 5a,b were found to exist as a syn and anti mixture of the enol form, while compounds 6a,b occurred as the enamine and methylene imine forms. The tautoraeric character and/or D-H exchange of the vinyl protons are described for compounds 5a,b and 6a,b .     

On triazoles XXIII [1]. The reaction of 5-amino-1,2,4-triazoles with thiacyclohexane β-oxo esters [2]

Six novel isomeric ring systems, namely the thiopyrano[4,3-d]-1,2,4-triazolo[1,5-a]pyrimidine, the thiopyrano[3,4-e]-1,2,4-triazolo[1,5-a]pyrimidine, the thiopyrano[3,4-d]-1,2,4-triazolo[1,5-a]pyrimidine, the thiopyrano[4,3-e]-1,2,4-triazolo[1,5-a]pyrimidine, the thiopyrano[3,2-d]-1,2,4-triazolo[1,5-a]pyrimidine and the thiopyrano[2,3-e]-1,2,4-triazolo[1,5-a]pyrimidine were synthesised. Spectroscopical evidence was given for the structure of compounds obtained.     

The synthesis of 11H-1,2,4-triazolo[4,3-b]pyridazino[4,5-b]indoles,11H-tetrazolo[4,5-b]pyridazino[4,5-b]indoles and 1,2,4-triazolo[3,4-f]-1,2,4-triazino[4,5-a]indoles

This paper describes the synthesis of the previously unknown 11H-1,2,4-triazolo[4,3-b]pyridazino[4,5-b]indoles (2) and 11H-tetrazolo[4,5-b]pyridazino[4,5-b]indoles (3) from 4-hydrazino-5H-pyridazino[4,5-b]indoles (1) , as well as the synthesis of 1,2,4-triazolo[3,4-f]-1,2,4-triazino-[4,5-a]indoles (10) from 2-indolecarbohydrazide (4) . Compounds 2 were obtained by acylation of compounds 1 , followed of thermal cyclization and compounds 3 by treating compounds 1 with nitrous acid. The reactions of compound 4 with formic acid or ethyl orthoformiate gave 1,2-dihydro-1-oxo-1,2,4-triazino[4,5-a]indole (6) . Treating this last compound with phosphorus oxychloride or phosphorus pentasulfide, followed by hydrazine, gave 1-hydrazino-1,2,4-triazino-[4,5-a]indole (9) . Acylation of this last compound, followed of cyclization gave compounds 10 . All the compounds were characterized by elemental analysis and ir and ¹H-nmr spectra.     

Heterocyclic β-Enamino esters. 28. The reaction of heterocyclic β-Enamino esters and nitriles with cyclic amidines. A simple route to azolopyrimidines

Whereas 2-amino-3-ethoxycarbonyl-4,5-dihydrofurans Ia-c condense with 5-membered amidine derivatives, via elimination of ethanol to afford the azolopyrimidines IIIa,b, XI, and XIVa,b, the 2-amino-3-cyano-4,5-dihydrofurans Id,e give with the same reagents, under elimination of ammonia, the novel ring systems of furo-azolopyrimidines XVIII and XXa,b. 2-Amino-3-ethoxycarbonyl-5,6-dihydro-4H-thiopyrane (XXI) reacts with 5-amino-1,2,4-triazole (II) to yield the triazolo[1,5-a]pyrimidine XXII, and with 2-aminobenzimidazole to XXIII. The mechanism of these reactions is discussed. XIVb and VIIb are cyclized in a secondary step to give the novel furo[2,3-d]benzimidazo[1,2-a]pyrimidine XXVI, and furo[2,3-d]-1,2,4-triazolo[1,5-a]pyrimidine XXVIII respectively, besides the acetoxy derivatives XVII and XXIX.     

Cyclocondensation of 6-acetyl-4,7-dihydro-5-methyl-7-phenyl[1,2,4]triazolo[1,5-a]pyrimidine with hydroxylamine and hydrazine

The cyclocondensation of 6-acetyl-4,7-dihydro-5-methyl-7-phenyl[1,2,4]triazolo[1,5-a]pyrimidine (3) with hydroxylamine or hydrazine leads to 3a,4,9,9a-tetrahydro-3,9a-dimethyl-4-phenylisoxazolo-[5,4-d][1,2,4]triazolo[1,5-a]pyrimidine ( 4a ) and 3a,4,9,9a-tetrahydro-3,9a-dimethyl-4-phenyl-1H-pyrazolo[3,4-d][1,2,4]triazolo[1,5-a]pyrimidine ( 4b ), respectively. In the presence of methanolic hydrogen chloride, 4b undergoes a cleavage of the pyrimidine ring to yield (5-amino-1,2,4-triazol-1-yl)(3,5-dimethylpyrazol-4-yl)phenylmethane ( 5 ). The structure determination of the compounds obtained is based on ¹H and ¹³C nmr spectra including NOE measurements.     

Recherches en série triazépine-1,2,4: II — Etude de la réaction de l'acétylacétate d'éthyle avec les diamino-3,4 oxo-5 dihydro-4,5 triazines-1,2,4

The reaction of 3,4-diamino-5-oxo-4,5-dihydro-l,2,4-triazine or its 6-methyl or 6-phenyl substituted derivatives and ethyl acetoacetate gave three compounds: 4,7-dioxo-9-methyl-1,4,6,7-tetrahydro-as-triazino[4,3-b]-1,2,4-triazepine in poor yield, isomeric 4,9-dioxo-7-methyl-1,4,8,9-tetrahydro-as -triazino[4,3-b]-1,2,4-triazepine and by competitive cyclisation, 2-methyl-7-oxo-3,7-dihydro-s-triazolo[3,2-c]-1,2,4-triazine. By condensation of 3-methylamino-4-amino-5-oxo-4,5-dihydro-1,2,4-triazine with ethyl acetoacetate, the formation of 4,9-dioxo-7,10-dimethyl-4,8,9,10-tetrahydro-as-triazino[4,3-b]-1,2,4-triazepine was strongly favored.     

Five-membered 2,3-dioxo heterocycles: LXXX. Recyclization of 1H-pyrrole-2,3-diones into pyrazolo[1,5-a]pyrimidines by the action of pyrazolamine. Crystalline and molecular structure of substituted pyrazolo[1,5-a]pyrimidine

Methyl 1-aryl-3-aroyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with 3-methyl-4-phenyl-1H-pyrazol-5-amine to give methyl 7-arylcarbamoyl-6-aroyl-2-methyl-3-phenylpyrazolo[1,5-a]-pyrimidine-5-carboxylates. The molecular and crystalline structures of methyl 6-benzoyl-7-(4-chlorophenylcarbamoyl)-2-methyl-3-phenylpyrazolo[1,5-a]pyrimidine-5-carboxylate were studied by X-ray analysis.     

Synthesis and chemical transformations of partially hydrogenated [1,2,4]triazolo[5,1-b]quinazolines

The reaction of 5-methyl-7-phenyl-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine with α,β-unsaturated carbonyl compounds in MeOH in the presence of MeONa affords partially hydrogenated aryl-substituted [1,2,4]triazolo[5,1-b]quinazolines. Hydrolysis, oxidation, reduction, and alkylation of 5,6,8-triphenyl-5,6,7,10-tetrahydro[1,2,4]triazolo[5,1-b]quinazoline were studied. The structure of one oxidation product, viz., 7-hydroxy-5,6,8-triphenyl-6,7-dihydro[1,2,4]triazolo[5,1-b]quinazoline, was established by X-ray diffraction. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 335—340, February, 2006.