الفهرس 
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Abstract
CHEMISTRY OF MERCAPTO- AND THIONE-
SUBSTITUTED 1,2,4-TRIAZOLES
Introduction:
There are three fundamental mercapto- and thione- substituted 1,2,4-triazole ring systems A-C1.
Mercapto-1,2,4-triazoles exist in two tautomeric forms, because the labile hydrogen may be attached either to the nitrogen or the sulfur atom. It exhibits thione- thiol tautomeric forms2,3 as shown above (system A).
The mercapto- and thione- substituted 1,2,4-triazole ring systems have been well studied and a variety of biological activities have been reported for a large number of their derivatives, such as antiproliferative4, antimicrobial4-7, antifungal4,8-17, antimalarial18, antibacterial19-25, antitubercular12,26, antimycobacterial27, anticancer4,28-30, diuretic31,32, hypoglycaemic33,34, antioxidant35, antiulcerogenic36, antidepressant37-39, anticonvulsant40-42, antiinflammatory43-46, antitumor47 and vasoconstriction48 activities.
Fused triazoles were also reported to possess significant biological activities49-53. For examples, 4-amino-5-cinchophenyl-3-thiol 1 and its fused thiatriazoles 2 and thiadiazoles 3 were exhibited good inhibitory effect against certain strains of pathogenic bacteria54, the triazolo-1,3,4-thiadiazoles 4 and the triazolo-1,3,4-thiadiazines 5 showed marked antibacterial and antifungal activities55.
Synthesis of Mercapto- and Thione-
Substituted 1,2,4-Triazoles
The main methods for synthesis of mercapto- and thione substituted 1,2,4-triazoles are the following:
1. from oxadiazole nucleus
The replacement of oxygen of oxadiazole nucleus with nitrogen atom yields triazole analogue56. Thus, 5-substituted-2-mercapto-1,3,4-oxadiazoles 6 were converted into 4-amino-3-mercapto-5-substituted-1,2,4-triazoles 7 upon heating with hydrazine hydrate57 or under microwave irradiation58.
The reaction may proceed by the nucleophilic attack of hydrazine on α-carbon atom of oxadiazole ring followed by dehydration59 as follows:
2. from acid hydrazides
2.1. By reaction with carbon disulfide
The condensation of the carboxylic acid hydrazides 8 with carbon disulfide in the presence of ethanolic potassium hydroxide yields the corresponding potassium 3-acyldithiocarbazates 9, which are converted to the corresponding 4-amino-5-substituted-3-mercapto-1,2,4-triazoles 7 via reaction with hydrazine upon heating57 or under microwave irradiation58. Alternatively, the cyclization of the 3-acyldithiocarbazates 9 via heating with aqueous potassium hydroxide yields the corresponding 5-substituted-2-mercapto-1,3,4-oxadiazoles 6, which yield the corresponding 4-amino-5-substituted-3-mercapto-1,2,4-triazoles 7 upon heating with hydrazine57.
Similarly, the triazoles 1060, 1161, 1262 and 1363 were prepared from the corresponding heterocyclic hydrazides which agitated with ethanolic potassium hydroxide and carbon disulfide to yield potassium 3-aroyldithiocarbazate salts which refluxed with hydrazine hydrate to give the corresponding 1,2,4-triazoles.
In addition, 5-substituted-3-mercapto-4H-1,2,4-triazoles 14 were prepared by the same method but the potassium salts 9 were refluxed with ammonia12.
2.2. By reaction with ammonium or potassium thiocyanate
The reaction of acid hydrazides 8 with ammonium or potassium thiocyanate in the presence of dilute hydrochloric acid led to the formation of the corresponding thiosemicarbazides 15 which were cyclized in alkaline media to yield the corresponding mercapto/thione-1,2,4-triazoles 1460,61,64,65.
Also, the reaction of acid hydrazide 16 with ammonium thiocyanate without solvent underwent cyclization to 1,2,4-triazole-5-thione 1766.
The 1,2,4-triazole derivatives 19 were synthesized from substituted hydrazide.