Green protocol for synthesis of the 3,5-disubstituted 1,2,4-thiadiazoles using N-benzyl-DABCO-tribromide in aqueous media

A novel and simple method for rapid conversion of thioamides to the corresponding 1,2,4-thiadiazole derivatives was developed. It was shown that, thioamides undergo clean and efficient oxidation and cyclization in their conversion to 1,2,4-thiadiazoles using N-benzyl-DABCO-tribromide in wet solid-solid conditions.     

Reaction of primary thioamides withp-toluenesulfinic acid

The conversion of thioamides to the corresponding 1,2,4-thiadiazoles occurs upon heating primary thioamides with formaldehyde andp-toluenesulfinic acid in water instead of the formation of N-(tosylmethyl)thioamides.M. V. Lomonosov State Academy for Fine Chemical Technology, 117571 Moscow, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 412–415, Marhc, 1997.     

An unexpected synthesis of 3,5-diaryl-1,2,4-thiadiazoles from thiobenzamides and methyl bromocyanoacetate

Aryl thioamides undergo very rapid condensation in the presence of methyl bromocyanoacetate to provide quantitative yields of 3,5-diaryl-1,2,4-thiadiazoles with an easy work-up and a high degree of product purity. The method can be scaled up with no loss in efficiency.     

tert-Butyl nitrite induced radical dimerization of primary thioamides and selenoamides at room temperature

A simple and efficient method for the dimerization of primary thioamides into 1,2,4-thiadiazoles using tert-butyl nitrite is described. The optimized condition was also found to be suitable for the dimerization of benzoselenoamides into 1,2,4-selenadiazoles. All the reactions proceed smoothly at room temperature and gave the desired products in excellent yields in a short span of time.     

Heterocyclization of derivatives of thioncarboxylic acids to 1,3,4-thiadiazoles under the action of tert-butyl hypochlorite

A method for synthesis of 2-alkyl-5-aryl- and 2,5-diaryl-1,3,4-thiadiazoles by successive reaction of thioamides with tert-butyl hypochlorite and benzothiohydrazides was developed. The first step in the formation of 1,3,4-thiadiazoles consists of oxidation of thioamides with tert-butyl hypochlorite with O atom transfer to the S atom, which was established by transformation of N-methyl-thiobutanamide into N-(methylimino)butanesulfenic acid.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 8, pp. 1843–1848, August, 1989.     

Regioselectivity of Alkylation of 3-Substituted 5-Amino-1,2,4-thiadiazoles

We have synthesized 3-substituted 4-alkyl-5-imino-4,5-dihydro-1,2,4-thiadiazoles by reaction of 3-alkyl(benzyl)thio-5-amino-1,2,4-thiadiazoles with methyl iodide or ethylene chlorohydrin. In the reaction with epichlorohydrin, addition of an oxirane molecule occurs with formation of tetrahydropyrimido[2,1-b]-1,2,4-thiadiazoles.     

Neue acetonylsubstituierte Azole II. 3-Acetonyl-1,2,4-oxadiazole, 2-Acetonyl-1,3,4-oxadiazole und 5-Acetonyl-1,2,4-thiadiazole

3-Acetonyl-1,2,4-oxadiazoles and 2-acetonyl-1,3,4-oxadiazoles are accessible starting with the ketal of acetoacetamide oxime and the ketal of acetoacetic acid hydrazide, respectively. 5-Acetonyl-1,2,4-thiadiazoles are obtained from 5-chloro-1,2,4-thiadiazoles andtert.-butyl acetoacetate. These Acetonyl-azoles are starting materials for three series of azolylvinyl phosphates and phosphonates.

Herrn Prof. Dr.Klaus Weissermel zu seinem 60. Geburtstag.     

Copper-catalyzed synthesis of 3-substituted-5-amino-1,2,4-thiadiazoles via intramolecular N–S bond formation

A copper-catalyzed N–S bond formation was utilized to produce 3-substituted-5-amino-1,2,4-thiadiazoles from imidoyl thioureas obtained by reaction of amidine hydrochlorides with isothiocyanates. Moreover, the 1,2,4-thiadiazoles were generated through a one-pot protocol without the isolation of the intermediates. This new method is highly efficient and convenient because it employs the cheap and environmentally friendly copper salt and can be conducted under air.     

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.     

Reactions of tetrasulfur tetranitride with bromomethyl ketones. One pot synthesis of 3,5-diaroyl- and 3,5-diacyl-1,2,4-thiadiazoles

Reactions of tetrasulfur tetranitride (S⁴N⁴) with aryl and alkyl bromomethyl ketones 1 in chlorobenzene at reflux temperature gave 3,5-diaroyl- and 3,5-diacyl-1,2,4-thiadiazoles 2 in 17-60% yields. No 1,2,5-thiadiazoles were detected. By heating of the two reactants at 115° without the solvent were also obtained 2 in 5-13% yields. Hydrolysis of 2 with sodium hydroxide in a mixture of ethanol, ethyl acetate, and water (v:v, 4:2:1) at 75° to 85° afforded the heretofore inaccessible 3-aroyl- and 3-acyl-1,2,4-thiadiazoles 3 in 17-79% yields.     

Thionation using fluorous Lawesson's reagent

[reaction: see text] Thionation of amides, 1,4-diketones, N-(2-oxoalkyl)amides, N,N'-acylhydrazines, and acyl-protected uridines with the use of a fluorous analogue of the Lawesson's reagent leads to thioamides, thiophenes, 1,3-thiazoles, 1,3,4-thiadiazoles, and acyl-protected 4-thiouridines. The isolation of the final products in high yields is achieved in most cases by a simple filtration (fluorous solid-phase extraction).     

An efficient one-pot synthesis of 3-substituted-5-amino-1,2,4-thiadiazoles from isothiocyanates and amidines

An efficient one-pot synthesis of 3-substituted-5-amino-1,2,4-thiadiazoles from isothiocyanates and amidines is described.     

Selenium heterocycles. XLIII. Syntheses of 3,5-Diaryl-1,2,4-thiadiazoles and 3,5-Diaryl-1,2,4-selenadiazoles

Starting from readily available α-arylsulfonyl-α-bromoacetophenones 2 a series of 3,5-diaryl-1,2,4-thiadiazoles and 3,5-diaryl-1,2,4-selenadiazoles were prepared in moderate yield. Reaction of compounds 2 with thiourea or selenourea gave 2-amino-5-arylsulfonyl-4-phenylthiazole or selenazole in good yield.     

Synthesis of 3-methyl-6-r-6h-thiazolo-[4,3-<Emphasis Type="Italic">b</Emphasis>]-1,2,4-triazolo[4,3-<Emphasis Type="Italic">d</Emphasis>]-1,3,4-thiadiazoles

A one-reactor method has been developed for the synthesis of 3-methyl-6-R-6H-thiazolo[4,3-b]-1,2,4-triazolo[4,3-d]-1,3,4-thiadiazoles by the condensation of aromatic aldehydes, thioglycolic acid, and 4-amino-5-methyl-1,2,4-triazole-3(2H)-thione in a sulfuric acid medium.     

Synthesis of 5,5′[[[3-(dimethylamino)propyl]imino]]bis[3-(trichloromethyl)-1,2,4-thiadiazole] and related thiadiazoles as antimalarial agents

The condensation of 5-chloro-3-(trichloromethyl)-1,2,4-thiadiazole (VIII) with N,N-dimelhyl-1,3-propanediamine gave 5-¶ [3-(dimethylammo)propyl]amino¶-3-(trichloromethyl)-1,2,4-thia-diazole(5) and 5,5′-¶[3-(dimethylamino)propyl]imino)¶bis[3-(triehloromethyl)-1,2,4-tliiadiazole] (14), together with 5,5′-[(3-¶ methyl[ 3-(trichloromethyl)-1,2,4-thiadiazol-5-yl ]amino Jpropyl)-imino]bis[3-(trichloromethyl)-1,2,4-thiadiazole] ( 17 ) which was formed via an unusual displacement of the distal methyl group of 14. The remarkable antimalarial activity of 14 prompted the synthesis of an array of 5-amino-3-(trichloromethyl, methyl, and 3,4-dichlorophenyl)-1,2,4-thiadiazoles and 5,5′-¶[(dialkylamino)alkyl]imino¶bis[3-(trichloromethyl, methyl, and 3,4-dichlorophenyl)-1,2,4-thiadiazoles] from an amine and the requisite 5-chloro-3-substituted-1,2,4-thiadiazoles, which were prepared from the appropriate amidine and trichloromethylsull'enyl chloride. 5-¶3-[(Diethylamino)methyl]-p-anisidino ¶-3-(triehloromethyl)-1,2,4-thiadiazole ( 13 ) was active against a chloroquine-resistant line of Plasrnodium berghei in the mouse, and compound 14 , the most promising member of the series overall, was designated for expanded antimalarial and toxicological studies. Structure-activity relationships against P. berghei in mice and P. gallinaceum in chicks are discussed.     

Synthesis of New Substituted 1,2,4-Triazoles and 1,3,4-Thiadiazoles and Their Effects on DNA Methylation Level

Russian Journal of General Chemistry - Continuing the search for biologically active compounds among functionally substituted azoles, new 1,2,4-triazole-3-thiols and 1,3,4-thiadiazoles derivatives...     

A Novel Route to 1,2,4-Triazoles

A novel synthetic method for the synthesis of 1,2,4-triazoles have been described starting from 1,3,4-thiadiazoles by adsorbing on acidic alumina under microwave irradiations (MWI).     

1,2,4-Thiadiazoles as promising multifunctional agents for treatment of neurodegenerative diseases

Detailed studies of properties of new 3-substituted 5-anilino-1,2,4-thiadiazoles containing different substituents at position 3 of the thiadiazole ring were carried out, in particular, their esterase profile and antioxidant properties. It was found that the presence in the molecule of 2-aminopropyl fragment determines an efficient and selective inhibition of butyrylcholinesterase as compared to acetylcholinesterase and carboxylesterase, with radical-scavenging activity being weak. The compounds containing a 2-aminopropenyl fragment possess a high radicalscavenging activity, weakly inhibit cholinesterases, and exhibit anticarboxylesterase activity. A wide spectrum of activity of 3-substituted 5-anilino-1,2,4-thiadiazoles as inhibitors of cholinesterases and highly efficient scavengers of free radicals gives a basis for the optimization of structure and development in this series of original agents for therapy of neurodegenerative diseases.     

Design,Synthesis, and Anti-Proliferative Activity of Some New Quinoxaline Containing 1,2,4-Thiadiazoles Amide Hybrids

Russian Journal of General Chemistry - A series of new quinoxaline-1,2,4-thiadiazoles amide hybrids has been synthesized and evaluated for their anti-proliferative activity on four different human...     

Annelation of the thiazole ring to 1,2,4-triazines by tandem AN—AN or SN H—SN H reactions

The reactions of 3-aryl-1,2,4-triazines with aromatic thioamides and 4-arylthiosemicarbazides in acetic anhydride at room temperature afforded cyclic products of the tandem nucleophilic addition reactions, viz., tetrahydrothiazolo[4,5-e]-annelated 1,2,4-triazines, in good yields. The latter underwent aromatization in the presence of potassium permanganate.