Synthesis of pyridine and 2,2′-bipyridine derivatives from the aza Diels-Alder reaction of substituted 1,2,4-triazines

Amidrazone 1a and the tricarbonyl derivatives 2b-d reacted in boiling ethanol in the presence of 2,5-norbornadiene 5 giving the pyridine derivatives 6b-d respectively (59-72%) and in the presence of 2,3-dihydrofuran 7 yielding the lactones 10b-d (39-44%). The 2,2′-bipyridine derivatives 6e-g were similarly obtained in good yield (81-87%) from the reaction of amidrazone 1b and tricarbonyl derivatives 2b-d in the presence of 2,5-norbornadiene 5.     

Synthesis of 6-[4-(allyl/phenyl)-5-thioxo-1,2,4-triazol-3-yl]pyrimidine-2,4-diones and their reaction with electrophiles

Cyclization of 1-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-6-yl)carbonyl-4-R-thiosemicarbazides in basic medium gave 6-(4-R-5-thioxo-1,2,4-triazol-3-yl)pyrimidine-2,4-diones (R = Allyl, Ph). Alkylation of the latter with iodomethane occurred at the sulphur atom to give the corresponding methylsulfanyl derivatives. Acetylation using acetyl chloride occurred at the N₍₁₎ atom of the triazole ring to the corresponding acetyl derivative when R = Ph but for R = Allyl the acetylation did not occur under the same conditions. In the presence of bromine in refluxing methanol the indicated allyl-substituted compound cyclizes to 6-bromomethyl-3-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-6-yl)-5,6-dihydrothiazolo[2,3-c]-1,2,4-triazole. Under Mannich and bromination conditions the methylsulfanyl derivatives prepared form derivatives at the 5 position of the uracil ring: 5-methylmorpholino-(piperidino)-and 5-bromo-(4-R-5-thioxo-1,2,4-triazol-3-yl)pyrimidine-2,4-diones respectively. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 906–912, June, 2006.     

Reaction of 4-Amino-3-methylthio-5-oxo-6-R-4,5-dihydro-1,2,4-triazines with Sulfonylacetic Acid Nitriles

The reactions of 4-amino-3-methylthio-5-oxo-6-R-4,5-dihydro-1,2,4-triazines with arylsulfonylacetonitriles and with dinitriles of sulfonyldiacetic acid and methylenebis(sulfonylacetic) acid have been studied. 7-Amino-3-R-8-(R'-sulfonyl)-1,4-dihydropyrazolo[5,1-c][1,2,4]triazin-4-ones have been synthesized and these are the first representatives of geminal sulfones in which the heterocyclic ring is bound directly to the sulfur atoms of the sulfonyl groups.     

1,2,4-Triazines in Organic Synthesis. 9. Synthesis of 3-(3-Ethylindol-2-yl)-5,6,7,8-tetrahydroisoquinoline Using the Fischer Reaction under the Usual Conditions and with Microwave Irradiation

The nucleophilic substitution of hydrogen in 3-methylthio-1,2,4-triazine by the carbanions of nitrobutane and 4-nitrobut-1-ene gave oximes, the selective fission of which using sodium dithionite gave ketones in the case of compounds with a saturated carbon chain. Ketones in Diels-Alder reaction with 1-pyrrolidinocyclohex-1-ene gave 3-acyl-1-methylthio-5,6,7,8-tetrahydroisoquinolines. Phenylhydrazones of the compounds obtained underwent Fischer reaction under usual conditions and also when using microwave irradiation on a solid support. The final 3-(3-ethylindol-2-yl)-5,6,7,8-tetrahydroisoquinoline was obtained via reductive desulfuration using Raney nickel in ethanol.     

微波作用下1-苯基-5-[5-(芳胺羰基甲硫基)-4-苯基-1,2,4-三唑-3-甲硫基]四唑的合成及生物活性

采用微波和相转移催化法通过1-苯基-5-(4-苯基-1,2,4-三唑-5-巯基-3-甲硫基)四唑(2)与2-氯乙酰芳胺(3)反应高效、快速地合成了10种尚未见文献报道的1-苯基-5-[5-(芳胺羰基甲硫基)-4-苯基-1,2,4-三唑-3-甲硫基]四唑. 其结构经 IR, ¹H NMR, ¹³C NMR 和元素分析表征. 生物活性实验结果表明, 该类化合物在较低浓度下部分化合物对小麦芽有很好的促进作用.     

The Reactions of 6-(tert-Butyl)-3-hydrazino-1,2,4-triazin-5(2H)-one with Carbonyl Compounds

The reaction of 6-(tert-butyl)-3-hydrazino-1,2,4-triazin-5(2H)-one with acetone and benzaldehyde yields the corresponding hydrazones. In the presence of thionyl chloride the benzaldehyde hydrazone is converted to 3-(tert-butyl)-6-phenyl-1,2,4-triazolo[4,3-b]-1,2,4-triazin-2(1H)-one and this can also be formed via the acylation of the starting hydrazinotriazinone using benzoyl chloride.     

Synthesis and opening of the thiadiazine ring in 6,7-dihydro-5H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines

A reaction of 3-benzylthiotriazole-4-amines with aromatic aldehydes leads to the formation of 6,7-dihydro-5H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines. A dihydrothiadiazine ring opening along the N-N bond occurs by the action of strong bases. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1249–1252, June, 2008.     

An MEDT study of the mechanism and selectivities of the [3+2] cycloaddition reaction of tomentosin with benzonitrile oxide

The [3+2] cycloaddition (32CA) reaction of tomentosin with benzonitrile oxide yielding a spiro-isoxazoline has been studied within the Molecular Electron Density Theory at the B3LYP/6-31(d,p) computational level. Given the multifunctionality of tomentosin, this 32CA reaction can take place along 16 competitive reaction paths. The chemo-, regio-, and stereoisomeric reaction paths involving the two C C double bonds of tomentosin have been studied. Density functional theory (DFT) calculations account for the total chemo- and regioselectivity, in complete agreement with the experimental outcomes, being suggestive of low diastereofacial selectivity. Analysis of the conceptual DFT indices accounts for the nonpolar character of this 32CA reaction. On the other hand, the topological analysis of the electron localization function of the selected points of the intrinsic reaction coordinate associated with the formation of the C C and C O single bonds emphasizes the zw-type reactivity of the phenyl nitrile oxide; the reaction taking place through a non-concerted two-stage one-step mechanism initialized with the formation of the C C single bond involving the β-conjugated carbon of tomentosin.     

An efficient one-pot synthesis of pyrazolyl-[1,2,4]triazolo[3,4-b][1,3,4] thiadiazin-6-yl)-2H-pyran-2-one derivatives via multicomponent approach and their potential antimicrobial and nematicidal activities

A series of simple or/and aryl, heteryl hydrazono pyrazolyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-6-yl)-2H-pyran-2-one derivatives have been efficiently synthesized in excellent yields via one-pot, multi-component approach. The importance of this methodology is that in a one-pot operation four new bonds (3C–N and 1C–S) are generated. The structure of compound 5a was confirmed by single-crystal X-ray diffraction. The newly synthesized compounds were evaluated for their in vitro antimicrobial activity against gram-positive bacteria (Staphylococcusaureus and Bacillussubtilis), gram-negative bacteria (Escherichiacoli andKlebsiellapneumoniae), antifungal activity against Candida albicans, and nematicidal activity against Meloidogyneincognita. Among all the compounds 6f showed excellent antimicrobial and nematicidal activity against tested bacteria, fungi, and nematodes.     

New synthetic approach to substituted isoindolo[2,1-a]quinoline carboxylic acids via intramolecular Diels-Alder reaction of 4-(N-furyl-2)-4-arylaminobutenes-1 with maleic anhydride

Acylation of substituted 4-(furyl-2)-4-arylaminobut-1-enes with maleic anhydride provided 2-allyl-6-carboxy-4-oxo-3-aza-10-oxatricyclo[5.2.1.0^1,5]dec-8-enes in high yield under mild reaction conditions. The Diels-Alder adducts are formed via an initial amide formation followed by a stereoselective intramolecular [4+2] exo-cycloaddition reaction. Treatment of the tricyclic compounds with phosphoric acid at high temperatures (70-120 °C) promoted cyclic ether opening, intramolecular cyclization and aromatization to give the corresponding tetracyclic compounds, 5,6,6a,11-tetrahydro-10-carboxyisoindolo[2,1-a]quinolines, in moderate yields. The influence of the acid and the reaction temperature on the cyclization reactions are also discussed.     

AlCl3-mediated tandem Friedel-Crafts reactions of vinylidenecyclopropanes with acyl chlorides: a facile synthetic method for the construction of 1-[2-(2,2-diarylvinyl)-1-phenyl-3H-inden-5-yl]ethanone derivatives

AlCl₃-mediated tandem Friedel-Crafts reaction of vinylidenecyclopropanes with acyl chlorides produced the corresponding 1-[2-(2,2-diarylvinyl)-1-phenyl-3H-inden-5-yl]ethanone derivatives in moderate to good yields under mild conditions within short reaction time.     

Synthesis,Structure and Cytotoxicity Testing of Novel 7-(4,5-Dihydro-1H-imidazol-2-yl)-2-aryl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-Imine Derivatives

The appropriate 1-arylhydrazinecarbonitriles 1a–c are subjected to the reaction with 2-chloro-4,5-dihydro-1H-imidazole (2), yielding 7-(4,5-dihydro-1H-imidazol-2-yl)-2-aryl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-imines 3a–c, which are subsequently converted into the corresponding amides 4a–e, 8a–c, sulfonamides 5a–n, 9, ureas 6a–I, and thioureas 7a–d. The structures of the newly prepared derivatives 3a–c, 4a–e, 5a–n, 6a–i, 7a–d, 8a–c, and 9 are confirmed by IR, NMR spectroscopic data, as well as single-crystal X-ray analyses of 5e and 8c. The in vitro cytotoxic potency of these compounds is determined on a panel of human cancer cell lines, and the relationships between structure and antitumor activity are discussed. The most active 4-chloro-N-(2-(4-chlorophenyl)-7-(4,5-dihydro-1H-imidazol-2-yl)-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)benzamide (4e) and N-(7-(4,5-dihydro-1H-imidazol-2-yl)-2-(p-tolyl)-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)-[1,1′-biphenyl]-4-sulfonamide (5l) inhibits the growth of the cervical cancer SISO and bladder cancer RT-112 cell lines with IC₅₀ values in the range of 2.38–3.77 μM. Moreover, N-(7-(4,5-dihydro-1H-imidazol-2-yl)-2-phenyl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)-4-phenoxybenzenesulfonamide (5m) has the best selectivity towards the SISO cell line and induces apoptosis in this cell line.     

Synthesis of 1H-pyrrolo[3,2-c]quinoline derivatives via palladium-catalyzed heteroannulation of 2-aryl-3-iodo-4-(phenylamino)quinolines and 4-(N,N-allylphenylamino)-2-aryl-3-iodoquinolines

Palladium(0)/copper iodide catalyzed Sonogashira cross-coupling of 2-aryl-3-iodo-4-(phenylamino)quinolines with terminal alkynes afforded series of 1,2,4-trisubstituted 1H-pyrrolo[3,2-c]quinolines in a single-step operation. Conversely, the 4-(N,N-allylphenylamino)-2-aryl-3-iodoquinoline derivatives were found to undergo PdCl₂(PPh₃)₂/CuI catalyzed intramolecular Heck reaction to yield the corresponding 1,3,4-trisubstituted 1H-pyrrolo[3,2-c]quinolines.     

Domino reaction of 3-nitro-2-(trifluoromethyl)-2H-chromenes with 2-(1-phenylalkylidene)malononitriles: synthesis of functionalized 6-(trifluoromethyl)-6H-dibenzo[b,d]pyrans and a rare case of [1,5] sigmatropic shift of the nitro group

A variety of functionalized 6-(trifluoromethyl)-6H-dibenzo[b,d]pyrans were easily synthesized in good yields under mild conditions by a domino reaction of 3-nitro-2-(trifluoromethyl)-2H-chromenes with 2-(1-phenylethylidene)- and 2-(1-phenylpropylidene)malononitriles. In the latter case, intermediate 7-amino-10-methyl-10-nitro-9-phenyl-6-(trifluoromethyl)-10,10a-dihydro-6H-benzo[c]chromene-8-carbonitriles were isolated as a result of a rare [1,5] sigmatropic shift of the nitro group.     

N,N'-二-[3-羟基-4-(2-苯并噻唑)苯基]脲的光谱实验与密度泛函理论研究

利用实验观测与密度泛函理论(DFT)计算方法考察了新化合物N, N'-二-[3-羟基-4-(2-苯并噻唑)苯基]脲(4-DHBTU)的红外、核磁与紫外吸收光谱性质.与单体2-(4-氨基-2-羟苯基)苯并噻唑(4-AHBT)相比, 4-DHBTU的实验紫外吸收强度显著增强,最大吸收峰发生了明显红移,并呈现出双吸收峰特征.结合实验光谱数据与密度泛函理论计算分析表明, 4-DHBTU分子最稳定的基态异构体为cis-C₁₁和trans-C₁₁,而导致上述紫外光谱差异的主要原因是4-DHBTU样品中cis-C₁₁, trans-C₁₁, cis-C₂₂, trans-C₂₂等多种异构体共存.此外, 4-DHBTU与溶剂二甲基亚砜(DMSO)间氢键作用使得核磁实验中4-DHBTU的15H、16H氢谱化学位移显著增大.     

Michael reaction of indoles with 3-(2′-nitrovinyl)indole under solvent-free conditions and in solution. An efficient synthesis of 2,2-bis(indolyl)nitroethanes and studies on their reduction

Michael reaction of 3-(2′-nitrovinyl)indole with eight 3-unsubstituted indoles on TLC-grade silica gel furnished unsymmetrical bis(indolyl)nitroethanes in 7-12 min under microwave irradiation and in 8-14 h at rt. In contrast, the p-TsOH-catalysed reaction of the nitrovinylindole with the 3-unsubstituted and two 3-substituted indoles in solution under reflux furnished both unsymmetrical and symmetrical bis(indolyl)nitroethanes, the latter resulting from novel tandem Michael addition-elimination-Michael addition reactions. The synthesis of a 2′,3″-bis(indolyl)nitroethane, the precursor core structure of two bioactive marine metabolites, and the reduction of 2,2-bis(3′-indolyl)nitroethane to the corresponding ethylamine, isolated as its N-acetyl derivative, have been achieved. Significantly, attempted hydrolysis of three nitronates, derived from the corresponding bis(indolyl)nitroethanes, with buffered aqueous TiCl₃ has led to the first isolation of oximes (syn/anti-mixture) as the only products.     

Synthesis and Properties of Derivatives of the new Heterocyclic System Benz[4,5]imidazo[1,2-c]pyrido[3',2';4,5]thieno[2,3-e]pyrimidine

Derivatives of a new heterocyclic system - benz[4,5]imidazo[1,2-c]pyrido[3',2';4,5]thieno[2,3-e]pyrimidine have been obtained by successive reactions in three stages - alkylation of 3-cyanopyridine-2(1H)-thiones with 2-chloromethylbenzylimidazole to give 2-benzimidazolylmethylthio-3-cyanopyridines, closing the thiophene ring in the latter to form 3-amino-2-(benzimidazolyl-2)thieno[2,3-b]pyridines, and cyclization of the pyrimidine ring by acylation with carboxylic acid anhydrides or chlorides.     

1-(5-萘酚-7-磺酸)-3-[4-(苯基偶氮)苯基]-三氮烯-溴化十六烷基吡啶-阴离子表面活性剂显色反应研究

合成了新试剂1 (5 萘酚 7 磺酸) 3 [4 (苯基偶氮)苯基] 三氮烯(NASA PAPT)。研究了在三乙醇铵介质中,阳离子表面活性剂溴化十六烷基吡啶(CPB)存在下,NASAPAPT与阴离子表面活性剂(AS)的显色反应。NASAPAPT与AS形成1∶3的紫红色络合物,络合物最大吸收位于588nm,表观摩尔吸光系数为1.06×104～1.14×104L·mol-1·cm-1。研究检测AS的新方法应用于废水分析,测定结果与经典分析结果吻合。     

Synthesis of 2-hydroxy-3-methylbut-3-enyl substituted coumarins and xanthones as natural products. Application of the Schenck ene reaction of singlet oxygen with ortho-prenylphenol precursors

Application of our original photooxidation-reduction methodology to prenylated dihydroxycoumarin and trihydroxyxanthone compounds led to the corresponding ortho-(2-hydroxy-3-methylbut-3-enyl)phenol derivatives with yields ranging from 8 to 65%. In most of the reported experiments, the oxidation products distribution, after the photooxygenation step, was controlled by the competition between the large group effect and the stabilising phenolic assistance effect. We also showed that ortho-(3-hydroxy-3-methylbut-1-enyl)phenol derivatives could be considered as biogenetic precursors of 2,2-dimethylbenzopyranic structures.     

Reactions of trimethinecyanines of the 1,3-dioxenium series with nucleophiles. The structures of the parent carbocation and of a product of its reaction with methanol

The chemistry and the regioselectivity of alcoholysis, aminolysis, and hydrolysis of symmetrical trimethinecyanine carbenium ions in 4-[3-(2,2-diorganyl-6-phenyl-4H-1,3-dioxen-4-ylidene) prop-1-enyl]-2,2-diorganyl-6-phenyl-1,3-dioxenium perchlorates (4a,b) were investigated. The structures of trimethinecyanine 4,5:4′,5′-bisannelated at the methine chain (3) and of a product of the reaction of nonannelated trimethinecyanine with the methoxide anion were established by X-ray diffraction analysis,¹H NMR spectroscopy, and quantum-chemical calculations (PM3). The nucleophile attacks the mesomeric π-conjugated system of the trimethinecyanine cation selectivily at the C(6) atom of one of the dioxenium fragrments, the second dioxenium ring being deactivated. Alcoholysis affords products of addition of the methoxy group to trimethinecyamines. In the course of aminolysis and hydrolysis, the dioxenium ring that is subjected to the attack eliminates acetone to form 1,3-dioxenylidenepropenylic derivatives of 1,3-enaminoketones and 1,3-ketoenols, respectively. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 521–529, March. 1999.