Multiple 1,2,3-thiadiazoles

A series of compounds 3a-d,i-n with two or three 1,2,3-thiadiazole rings, useful for photocrosslinking processes, was prepared from the di- or triketones 1a-d,i-n via the corresponding hydrazones 2a-d,i-n by applying the Hurd-Mori method. A special synthetic sequence, 1e, 2e, 3e, 3f/3g , was elaborated for the olefinic system 3h.     

The Synthesis of 4-Carbalkoxy-5-thioalkyl-1,2,3-thiadiazoles

The reaction of 1,1-dithiomalonates 2 with p-toluenesulfonyl azide provided 1,2,3-thiadiazoles 4 in excellent yield.     

Anomalous rearrangement of 1,2,3-thiadiazoles to 1,2,3-triazoles

The rearrangement of 5-amino-1,2,3-thiadiazoles under the influence of halogen-containing oxidizing to bis(triazolyl) disulfides was observed. Ammonia reduces the disulfides obtained to 5-mercapto-1,2,3-triazoles.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 840–846, June, 1993.     

Nucleophilic substitution in 1,2,3-thiadiazoles

By reactions of nucleophilic substitution of the halogen atom in 5-halo-1,2,3-thiadiazoles (IV), we have obtained 5-amino- (I, V), hydrazino-(VI, VII, IX, X), and mercapto- (VIII) 1, 2, 3-thiadiazoles. We show that upon reaction with amines, a mixture of 5-amino-1, 2, 3-thiadiazoles (I) and 5-mercapto-1, 2, 3-triazoles (II) is formed, and also the reaction product of compounds I and IV,: the selectivity of this process depends only on the type of solvent.Organic Synthesis Technology Department, Urals State Technical University—UPI, Ekaterinburg 620002. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 554–559, April, 1994. Original article submitted February 28, 1994.     

Selenium-sulfur analogs 2. Synthesis and characterization of 4-aralkyl-1,2,3-selenadiazoles and -1,2,3-thiadiazoles

1 The3-diketones 5 and 8 were alkylated with methyl iodide to give the nonenolizable diketones 6 and 9 which condensed with semicarbazide hydrochloride yielding the monosemicarbazones 7 and 10 . Cyclization with selenous acid or with thionyl chloride led to the corresponding 1,2,3-selenadiazoles 3a , 4a , and 1,2,3-thiadiazoles 3b , 4b .     

Synthesis of 4-thioacetyl-1,2,3-thiadiazoles. Reversible rearrangement of N-Substituted 5-methyl-1,2,3-thiadiazole-4-carbothioamides

The equilibrium in the reversible rearrangement of 5-methyl-1,2,3-thiadiazole-4-carbothioamides into 5-amino-4-thioacetyl-1,2,3-thiadiazoles is displaced toward the former, and polar solvents favor increased fraction of the thioketone.     

Dimroth rearrangement of 5-hydrazino-1,2,3-thiadiazoles

The reversible isomerization of 5-hydrazino-1,2,3-thiadiazoles and 1-amino-5-mercapto-1,2,3-triazoles has been established for an ester function at the 4-position ( 4a ? 5a ). Thus, 4a was isolated by reacting 3a with two equivalents of hydrazine, whereas 5a resulted when an excess of hydrazine was used. Acid treatment of 5a yielded 4a again, and its hydrazone 8 was obtained from 5a and benzaldehyde. Compound 5a was also converted into the derivatives 6a, 7, 9 and 10a-c. The less reactive 5-chloro-1,2,3-thiadiazoles 3b,c afforded the bis-heterocycles 6b,c on heating with hydrazine.     

N-15 NMR analysis of 1,2,3-thiadiazoles

The ¹⁵N nmr spectra of a series of 1,2,3-thiadiazoles reveal the strong influence of substituents at C-5 on the N-2 resonance. Upon methylation, the two thiadiazole nitrogen resonances are shielded, but the most dramatic shift is observed for the methylated nitrogen, Δδ > 140 ppm. The ¹⁵N chemical shifts of some mesoionic thiadiazoles were also determined and explained by the dual effect of 5-substitution and salt formation. By disconnecting these effects, the ¹⁵N chemical shifts of 10 and 11 were found to be unusual and to reflect a thiapentalene character.     

Carbon-13 Nmr spectra of 1,2,3-thiadiazoles

Natural abundance ¹³C nmr spectra are reported for 1,2,3-thiadiazole and nine derivatives. The spectra are discussed in terms of α- and β-effects of substituent groups and compared with corresponding spectra of alkene and benzene derivatives. ¹³C nmr spectra of four 1,3,4-thiadiazoles are presented. Spectral data indicate that in dimethylsulfoxide solution 2-mercapto-5-methyl-1,3,4-thiadiazole exists predominantly as the thione tautomer.     

Mass spectra of 4,5-disubstituted 1,2,3-thiadiazoles

The schemes of the fragmentation of 4-substituted 5-arylamino-1,2,3-thiadiazoles were established on the basis of electron-impact mass spectra and high-resolution mass-spectrometric data, and the effect of substituents on the fragmentation pathways was analyzed. It is shown that the cyclization of the [M-N₂]⁺ ions formed in the fragmentation of compounds that contain a thiocarboxamido group in the 4 position proceeds with the participation of the most nucleophilic heteroatom.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 118–122, January, 1988.     

Recent trends in the synthesis of 1,2,3-thiadiazoles

Abstract

1,2,3-Thiadiazoles, structurally active pharmacophores have attracted significant attention of synthetic chemists, medicinal and pharmaceutical researchers because of their versatile biological activities against various diseases such as herbicidal, insecticidal, antiviral, antitumor, antimicrobial, anticancer, plants activator and anti-amoebic activities. A literature survey of the last decade presented in this review article summarizes the major synthetic approaches, methodologies and strategies adopted for the synthesis of 1,2,3-thiadiazole scaffolds which will be help for medicinal chemists and pharmacists in future synthesis and development of novel therapeutic agents.     

Reaction of 5-halo-1,2,3-thiadiazoles with aliphatic diamines. Synthesis and intramolecular cyclization of bis(1,2,3-triazolyl-1,2,3-thiadiazolyl)sulfides

Bis[1,2,3]triazolo[1,5-f:5',1'-b][1,3,6]thiadiazepine and [1,5-g:5',1'-b][1,3,7]thiadiazocine ring systems have been synthesized from 5-halo-1,2,3-thiadiazoles and aliphatic diamines. We have found that the last step of the process is the cyclization of initially formed bis(1,2,3-triazolyl-1,2,3-thiadiazolyl)sulfides. The structures of the intermediates and products were supported by different NMR spectroscopic methods (1H coupled 13C NMR, 2D HETCOR, HMBC and 1D INADEQUATE experiments) and mass spectrometry. Differences in the reaction pathway for aliphatic and less nucleophilic aromatic diamines were determined.     

Mass-spectrometric study of isomeric 5-amino-1,2,3-thiadiazoles and 5-mercapto-1,2,3-triazoles

The behavior of the isomeric 5-amino-1,2,3-thiadiazoles and 5-mercapto-1,2,3-triazoles under electron impact was studied. It was shown that mass spectrometry can serve as a rapid and reliable method for the identification of these compounds. Key factors in the assignment of a compound to one or the other class are the peaks of the [M-N₂]⁺ ions, which are more intense in the case of the thiadiazoles, and the ions determined by the decomposition of the prototropic forms of the triazoles. The compositions of the ions were determined by the high-resolution mass spectra.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 681–689, May, 1987.     

1,2,3-thiadiazoles. I. Synthesis of sodium (or potassium) 1,2,3-thiadiazole-4-thiolates via thiocarbazonate esters and N-acylthiohydrazonate esters

A general synthesis of 1,2,3-thiadiazole-4-thiolates 1 and their derivatives 2–3 by an extension of the Hurd-Mori 1,2,3-thiadiazole synthesis is described. Treatment of methyl (or ethyl) [1-(alkylthio)alkylidene]hydrazinocarboxylates 11 (thiocarbazonate esters) or other N-acylthiohydrazonate esters [Y = ureido ( 12 ) or arenesulfonyl ( 13 )] with thionyl chloride affords 2–3 efficiently. Intermediates 11–13 are readily obtained from the N²-thioacylcarbazates 8 , N³-thioacylsemicarbazides 9 , or N²-thioacyl-N¹-(p-toluenesulfonyl)hydrazides 10 , respectively, by S-alkylation. Physicochemical properties of the 1,2,3-thiadiazoles 1–3 and N-acylthiohydrazonate esters 11–13 are also described.     

Acylation of 2-aryl-5-imino-2,5-dihydro-1,2,3-thiadiazoles

A large series of new 5-acyl-and 5-sulfonylthiadiazolimines was prepared by acylation of 2-aryl-5-imino-2,5-dihydro-1,2,3-thiadiazoles. Compounds obtained are more stable than the initial substances and do not transform into 1,2,4-thiadiazoles.