Use of Tetramethylthiuram Disulfide in Synthesis of Nitrogen-containing Heterocyclic Compounds

We have developed a method for synthesis of aryl isothiocyanates by means of thiocarbamoylation of aromatic amines by tetramethylthiuram disulfide followed by degradation of the intermediate N₍₁₎-aryl-N,N-dimethylthiourea by concentrated HCl. We have shown that thiocarbamoylation of 4-amino-5-ethyl-4H-1,2,4-triazole-3-thiol occurs at the 2 position of the triazole ring, while thiocarbamoylation of 4-amino-3-methyl-6-phenyl-4,5-dihydro-1,2,4-triazin-5-one leads to the dihetaryl-substituted thiourea. We consider the possibility of using N₍₁₎-aryl-N,N-dimethylthioureas as analogs of isothiocyanates in reactions with N-nucleophiles.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 775–780, May, 2005.     

Synthesis and Pesticidal Properties of Thio and Seleno Analogs of Some Common Urea Herbicides

Thio and seleno analogs of fenuron, isoproturon, chlorotoluron, metoxuron, monuron, and diuron were synthesized from the corresponding aryl amines. Their reaction with thiophosgene leads to isothiocyanates. Aryl amines were also converted (via isocyanides) to isoselenocyanates. The reaction of both isothio- and isoselenocyanates with dimethylamine affords the corresponding thio and seleno analogs of the above-mentioned urea herbicides. Herbicidal activity of the synthesized compounds was slightly lower than the activity of the parent urea herbicides. The thio and seleno analogs as well as the parent ureas showed good fungicidal activity at a concentration of 200 ppm against selected fungi.     

TMEDA-CATALYZED SYNTHESIS OF N-ARYL-N′-ETHOXYCARBONYL THIOUREA AND ARENE (OR POLYMETHYLENE)-BIS-ETHOXYCARBONYLTHIOUREA DERIVATIVES

A novel and efficient method for synthesis ethoxycarbonyl isothiocyanate and ethoxycarbonyl thioureas catalyzed by TMEDA is reported. A series of N-aryl-N′-ethoxycarbonyl thioureas and arene (or polymethylene)-bis-ethoxycarbonyl thiourea derivatives have been synthesized in good-to-excellent yields via this method at room temperature.     

Efficient Method of Synthesis of N,N′-Disubstituted Ureas/Thioureas by a Zinc Chloride Catalyzed Thermal Reaction

Symmetrically N,N′-disubstituted ureas/thioureas were synthesized by heating amines or phenyl hydrazine and urea/thiourea on a preheated hot plate at 80–85°C under solvent-free conditions in the presence of a catalytic amount of ZnCl₂ as a catalyst. The protocol has the advantages of not using toxic phosgene and other hazardous substrates or organic solvents. Increased reaction rate, good yield, and a simple workup procedure are involved.     

Sultam Thioureas Synthesized via an Alternative Ring-Forming Reaction

A method for the synthesis of sultam thioureas via a different 1,4,2-dithiazolidine 1,1-dioxide ring-forming reaction is presented here. The syntheses of nine sultam thioureas were achieved in 53–81% yield by reacting N-substituted chloromethanesulfonamides with thiocarbamoyl isothiocyanates, which were formed in situ from the reaction of 5-(disubstituted amino)-3H-1,2,4-dithiazole-3-thiones with triphenylphosphine. Importantly, this method successfully allowed the substituent of the ring nitrogen atom to be varied. Additionally, the structures of four sultam thioureas were confirmed by x-ray diffraction.     

Hydrogen Peroxide–Promoted Transformation of Thioureas/Thiosemicarbazides to Related Ureas/Semicarbazides at Room Temperature via Grinding

A novel and environmentally benign synthetic method for ureas through hydrogen peroxide–promoted desulfurization of thioureas at room tepemperature via grinding is reported. As compared with the traditional method, this one is manipulatively simple and the oxidant is low cost, highly active, and environmentally friendly.     

Regioselective synthesis of thiophene fused sultam derivatives via iodocyclization approach and their application towards triazole linker

An efficient regioselective synthesis of 4-iodo-2,3-disubstituted-2H-thieno[3,2-e][1,2]thiazine-1,1-dioxide derivatives via iodocyclization approach using iodine under mild reaction condition described herein. This coupling–iodocyclization strategy tolerated a variety of functional groups such as alkyl, cycloalkyl, phenyl producing the six-membered heterocyclic ring selectively. The resulting 4-iodo-2,3-disubstituted-2H-thieno[3,2-e][1,2]thiazine-1,1-dioxide was coupled with a variety of boronic acids (Suzuki coupling) and activated alkenes (Heck coupling). The iodo group was utilized for Sonogashira coupling followed by efficient transformation to azido precursor, which was used for the synthesis of various thieno-sultam linked with triazole.     

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.     

相转移催化法合成双3－苯丙烯酰基取代硫脲及双3－苯丙烯酰基取代胺衍生物

以3－苯丙烯酸为原料，经酰氯化，得到3－苯丙烯酰氯，在PEG－400为催化剂 的固液相转移催化条件下与硫氰酸铵及二胺类反应，一锅法制得双3－苯丙烯酰基 取代硫脲化合物。3－苯丙烯酰氯在PEG－600为催化剂的液液相转移催化条件下和 二胺类反应得到双－苯丙烯酰基取代胺化合物。反应条件温和、产率高。化合物经 元素分析、IR及^1H NMR证实。初步的生理活性研究表明，部分化合物具有良好的 抗炎活性。     

莰烷磺内酰胺法合成（R）和（S）黄粉虫性引诱信息素

不对称烷基化反应;莰烷磺内酰胺法合成（R）和（S）黄粉虫性引诱信息素