Synthesis ofβ-chloroethylamino derivatives in the 1,3,4-thiadiazole series. I

A study is made of the hydroxyethylation of some 2-amino-5-aryl-1,3,4-thiadiazoles and replacement of the hydroxyl group in the hydroxyethylation products by chlorine, as well as of condensation of p-[di(β-chloroethyl)amino]phenylacetyl chloride with the 2-amino-5-aryl-1,3,4-thiadiazoles.     

The synthesis and cyclisation of thioacylated diaminoguanidines

The thiobenzoylation of 1,2-diaminoguanidine yields 1-amino-2-thioaroylamidoguanidines which are isolable as their stable hydrazones. They are unaffected by alkalis, but are cyclised by mineral acids, with loss of ammonia, to hydrazones of 2-aryl-5-hydrazino-1,3,4-thiadiazoles, or with elimination of hydrazine, to the appropriate 2-amino-5-aryl-1,3,4-thiadiazoles. The action of acetic anhydride effects the same ring-closures, yielding the corresponding acetylated products. 1,2-Diamino-3-phenylguanidine undergoes a comparable series of reactions.     

Synthesis of 2-amino-5-aryl-1,3,4-thiadiazoles and their condensed analogs with the use of aromatic nitrites

Aromatic nitrites are found to readily react with thiosemicarbazide and 4-amino-3-methyl-1,2,4-triazol-5-thione in a solution of polyphosphoric acid to give corresponding 2-amino-5-aryl-1,3,4-thiadiazoles.     

A convenient and general synthesis of 2-amino-1,3,4-thiadiazoles. Dehydration of acylthiosemicarbazides with methanesulfonic acid

2-Amino-5-alkyl and 2-amino-5-aryl-1,3,4-thiadiazoles were prepared by the dehydration of 2-acylthiosemicarbazides with molar equivalents of methanesulfonic acid in refluxing toluene. The synthesis appears to be general.     

Synthesis of 5-fluoro-2-methyl-3-(2-trifluoromethyl-1,3,4-thiadiazol-5-yl)-4(3H)-quinazolinone and related compounds with potential antiviral and anticancer activity

The synthesis of ten new substituted 1,3,4-thiadiazolyl-4(3H)-quinazolinones 8–11, 13, 17 , and 20–23 is reported. Compounds 8–11 were prepared by condensation of 5-fluoro-2-methyl-3,1-benzoxazin-4-one (3) and 5-substituted 2-amino-1,3,4-thiadiazoles 4–7. Compound 13 was obtained by condensation of 5-fluoro-2-methyl-3,1-benzoxazin-4-one (3) with DL-α-amino-?-caprolactam (12) . Compound 17 was synthesized by condensation of 6-bromo-2-methyl-3,1-benzoxazin-4-one (16) and 2-amino-5-t-butyl-1,3,4-thiadiazole (5) . Compounds 20–23 were obtained by condensation of 5-chloro-6,8-dibromo-2-methyl-3,1-benzoxazin-4-one (19) and 5-substituted 2-amino-1,3,4-thiadiazoles 4–7, respectively. The substituted 3,1-benzoxazin-4-ones 3, 16, and 19 were obtained in good yield by refluxing the appropriate anthranilic acid, 1,15 , and 18 with acetic anhydride (2) .     

Reactivity of 2-amino-1,3,4-thiadiazoles. Nucleophilic behaviour of some 2-amino-1,3,4-thiadiazoles: Model compounds

The ambident nucleophilic behaviour of some 2-amino-5-H-1,3,4-thiadiazoles in alkylation, acylation and nitrosation reaction has been verified. The structures assigned to the 2-amino-1,3,4-thiadiazoles ( 1a-i ) and to the Δ²-1,3,4-thiadiazolines ( 2a-e ) agree with the spectral data.     

Concerning the “synthesis of 2-amino-5-aryl-5H-thiazolo[4,3-b]-1,3,4-thiadiazoles”

Compounds described previously as 2-amino-5-aryl-5H-thiazolo[4,3-b]-1,3,4-thiadiazoles were found to be thiosemicarbazones of aromatic aldehydes. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya No. 6, pp. 1228–1229, June, 1997.     

3-芳基-6-对甲苯甲酰氨基均三唑并[3,4-b]-1,3,4-噻二唑的合成及生物活性

利用3-芳基-4-氨基-5-巯基-1,2,4-均三唑和对甲苯甲酰异硫氰酸酯在乙腈中反应, 得到一系列3-芳基-6-对甲苯甲酰氨基均三唑并[3,4-b]-1,3,4-噻二唑, 用¹H NMR, IR, MS和元素分析确定了其结构, 并对其进行了抗菌活性测试.     

Syntheses of arylsulfonyl-1,3,4-thiadiazoles

Reaction of sodium arylsulfinate with 2-aryl-5-chloro-1,3,4-thiadiazole gave 2-aryl-5-arylsulfonyl-1,3,4-thiadiazole (3) in good yield. Starting from readily available 2-amino-5-benzylmercapto-1,3,4-thiadiazole compound 7 was obtained in three steps in moderate yield. Reaction of compound 7 with sodium arylsulfinate afforded 2,5-diarylsulfonyl-1,3,4-thiadiazole ( 11 ). Oxidation of compound 10 with hydrogen peroxide in acetic acid gave 2-arylsulfonyl-5-benzylsulfonyI-1,3,4-thiadiazole ( 12 ), in high yield.     

Synthesis of 6-aryl substituted 3-(5''''-phenyl-2H-tetrazole-2''''-methylene)-S-triazolo[3,4-b]-1,3,4-thiadiazoles

In this paper , 10 novel 6-aryl-3-(5'-phenyl-2H-tetrazole-2'-methylene)-S-triazolo[3, 4-b]-1,3,4-thiadiazoles have been synthesized by the condensation of 3-(5'-phenyl-2H-tetrazole-2'-methylene)-4-amino-5-mercapto-1,2,4-triazole with various aromatic carboxylic acids in the presence of phosphorus oxychloride. The structure of these compounds was determined by elemental analysis , UV, IR, 1H NMR and MS. Their spectral properties were also discussed.     

One-pot synthesis of 2-amino- 5-aryl -5H-thiazolo[4,3-b]-1,3,4-thiadiazoles

Equimolar mixtures of aromatic aldehydes with thioglycolic acid and thiosemicarbazide in H₂SO₄ transform into 2-amino-5-aryl-5H-thiazolo[4,3-b]-1,3,4-thiadiazoles.Translated fromIzvestiya Akademioi Nauk. Seriya Khimicheskaya, No. 3, pp. 763–764, March, 1996.     

3-芳基-6-对氯苯甲酰氨基均三唑并[3,4-b]-1,3,4-噻二唑的 合成及生物活性

利用3-芳基-4-氨基-5-巯基-1,2,4-均三唑和对氯苯甲酰异硫氰酸酯在乙腈中反应, 得到一系列3-芳基-6-对氯苯甲酰氨基均三唑并[3,4-b]-1,3,4-噻二唑, 用1H NMR, IR, MS和元素分析确定了其结构, 并对其进行了抑菌活性测试.     

The reaction of N-R-2-cyanothioacetamides with ethyl[(aryl)hydrazono]chloroacetates

Depending on the nature of the substituents in the starting reagents and the basicity of the medium the cyclization of N-R-2-cyanothioacetamides with ethyl [(aryl)hydrazono]chloroacetates gives 3-aryl-2-cyanomethylidene-5-ethoxycarbonyl-1,3,4-thiadiazoles, 5-arylhydrazono-2-cyanomethylidene-3-phenyl-thiazolidin-4-ones, di[(aryl)hydrazono](ethoxycarbonylmethyl) sulfides, and 5-amino-3-cyano-2-phenyl-amino-4-(N-phenylaminothiocarbonyl)thiophene. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp 109–114, January, 2007.     

Studies on Condensed Heterocyclic Compounds XVII. Synthesis of 6-(1-Aryl-5-methyl-1,2,3-triazol-4-yl)-3-phenyl-s-triazolo[3,4-b]-1,3,4-thiadiazoles

Treatment of 4-amino-5-mercapto-3-phenyl-1,2,4-triazole 2 with 1-aryl-4-carboxy-5-methyl-1,2,3-triazoles 1a-1j in a one-step reaction yielded several 6-(1-aryl-5-methyl-1,2,3-triazol-4-yl)-3-phenyl-s-triazolo[3,4-b]-1,3,4-thiadiazoles 3a-3j . The structures of all the products were established on the basis of elemental analyses and spectral data. The fragmentation of the mass spectra of 3a-3j under electron impact was discussed.     

Anodic formation of 3,6-diaryl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles and 2(3-aryl-5-methyl-1H-[1,2,4]triazol-1-yl)-5-aryl-1,3,4-thiadiazoles

3,6-Disubstituted 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles together with the unknown systems 2-(3-aryl-5-methyl-1H-[1,2,4]triazol-1-yl)-5-aryl-1,3,4-thiadiazoles were obtained by anodic oxidation, under aprotic conditions, of aryl aldehyde N-(5-aryl-1,3,4-thiadiazol-2-yl) hydrazones. Mechanistic proposals are given.     

Syntheses of 3-[5-Methyl-1-(4-Methylphenyl)-1,2,3-Triazol-4-yl]-6-Substituted-s-Triazolo[3,4-b]-1,3,4-Thiadiazoles

1,2,3-Triazole derivatives have been reported as inhibiting tumor proliferation, invasion, and metastasis^[1]. The fused l,3,4-triazolo[3,4-b]-1,3,4-thiadiazoles derivatives show various biological effects such as antifungal^[2], antibacterial, hypotensive and CNS depressant activities^[3]. We have reported several 6-aryl-3-[5-methyl-1-(4-methylphenyl)-1,2,3-triazol-4-yl]-s-triazolo[3,4-b]-1,3,4-thiadiazoles in the previous paper^[4]. The novel 6-aryl-3-[5-methyl-1-(4-methylphenyl)-1,2,3-triazol-4-yl]-s-triazolo[2,4-b]-1,3,4-thiadiazoles 6a-j have been synthesized by the condensation of 4-amino-5-mercapto-3-[5-methyl-1-(4-methylphenyl)-1,2,3-triazol-4-yl]-s-triazole 5 with various aromatic carboxylic acids in the presence of phosphorus oxychloride. The mercaptotriazole 5 was prepared from 4,the latter being prepared from 1 throng 2 and 3. The title compounds 6 were depicted in scheme 1. The structures of these compounds were established by elemental analysis, NMR, MS and IR techniques.     

SYNTHESIS OF 2-AROYLAMINO-5-ARYLOXYMETHYL-1,3,4-THIADIAZOLES UNDER LIQUID-LIQUID PHASE TRANSFER CATALYSIS

2-Aroylamino-5-aryloxymethyl-1,3,4-thiadiazoles (I _1–20 ) are synthesized by the condensation of 2-amino-5-aryloxymethyl-1,3,4-thiadiazoles with aroyl chlorides in the presence of PEG-400 phase transfer catalyst.     

Basicity and mechanism of transmission of electronic effects of substituents in the series of 2-amino-5-aryl-1,3,4-thiadiazoles

The basicity of 2-amino-5-aryl-1,3,4-thiadiazoles was studied. A correlation was obtained between the pK_BH+ values of the compounds and the constants of the substituents. It was shown that the electronic effects of the substituents in the phenyl ring are transmitted both on account of conjugation and by an induction mechanism.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 267–270, February, 1987.     

2-Azido-1,3,4-thiadiazoles, 2-Azido-1,3-thiazoles,and Aryl Azides in the Synthesis of 1,2,3-Triazole-4-carboxylic Acids and Their Derivatives

Diazotization of 2-amino-1,3,4-thiadiazoles gave 1,3,4-thiadiazole-2-diazonium sulfates which were converted to 2-azido-1,3,4-thiadiazoles. The latter reacted with ethyl acetoacetate in the presence of sodium methoxide in methanol to produce 1-(5-R¹-1,3,4-thiadiazol-2-yl)-5-R²-1H-1,2,3-triazole-4-carboxylic acid derivatives. The reactions of 2-azido-5-methyl-1,3,4-thiadiazole and 2-azido-1,3-thiazole with ethyl 3-(1,3-benzodioxol-5-yl)-3-oxopropanoate led to the formation of 1,2,3-triazole ring under milder conditions (K₂CO₃, DMSO). Various 1,2,3-triazole-4-carboxylic acid derivatives were synthesized.