Monatshefte fu ¨r Chemie 139, 153–159 (2008) DOI 10.1007/s00706-007-0764-5 Printed in The Netherlands Heterocyclic Synthesis with 4-Benzoyl-1-cyanoacetylthiosemicarbazide: Selective Synthesis of Some Thiazole, Triazole, Thiadiazine, Pyrrylthiazole, and Pyrazolo[1,5-a]triazine Derivatives Samir Bondock  , Abd El-Gaber Tarhoni, and Ahmed A. Fadda Department of Chemistry, Faculty of Science, Mansoura University, Mansoura, Egypt Received June 26, 2007; accepted July 5, 2007; published online January 11, 2008 # Springer-Verlag 2008 Summary. 4-Benzoyl-1-cyanoacetylthiosemicarbazide un- dergoes coupling reaction with aromatic diazonium chloride to afford (arylhydrazono)thiosemicarbazide, which was reacted with phenacyl bromide regioselectivity to afford the thia- zoline. The (arylhydrazono)thiosemicarbazide could be trans- formed into the pyrazolo[1,5-a]triazine. Heterocyclization of 4-benzoyl-1-cyanoacetylthiosemicarbazide with -haloke- tones (bromoacetone and phenacyl bromide), ethyl iodide, and ethyl bromoacetate furnished the pyrrylthiazoles, 1,2,4- triazole, and 1,3,4-thiadiazine. The latter was coupled with aromatic diazonium chloride to give the bis(arylhydrazono)- thiadiazine. The mechanism for the formation of the title compounds was suggested and discussed. Keywords. Thiosemicarbazide; -Haloketones; Thiazoline; Triazole; Thiadiazine. Introduction The cyclization of thiosemicarbazides has been shown to be an excellent strategy for the synthesis of sev- eral heterocycles like 1,2,4-triazoles, 1,3,4-thiadi- azoles, 1,3,4-oxadiazoles, and (or) 1,3,4-triazines [1–4]. For instance, the cyclization of 1,4-disubsti- tuted thiosemicarbazides resulted in the formation of 1,3,4-thiadiazoles in acidic media [5, 6]. On the oth- er hand, the same thiosemicarbazides underwent a cyclization to yield 1,2,4-triazole derivatives in the presence of sodium hydroxide [7, 8]. Alkylation of thiosemicarbazides with -halocar- bonyl compounds may result in the formation of five- and six-membered isomeric heterocycles [9]. Although a large number of papers [10–13] deals with the reactions of thiosemicarbazide with -halo- ketones, it is rather difficult to predict the structure of the condensation products when new thiosemicar- bazides as well as -haloketones are used. The anal- ysis of literature data shows that in such reactions possible products are thiadiazines, thiazoles, thiazo- lines, pyrazoles, and other compounds, depending on the nature of the substituent both in the -halocar- bonyl compound and in thiosemicarbazide, as well as on the reaction conditions, i.e. the pH of the medium, temperature, solvent, reagent addition or- der, etc. [14–17]. As a part of our program aimed at the develop- ment of new simple and efficient procedures for the synthesis of some important heterocyclic systems from thiosemicarbazide derivatives, we have recent- ly reported different successful approaches for the synthesis of thiazole, thiadiazole, and thiobarbituric acid derivatives [18–20]. In continuation of our interest in the synthesis of novel heterocycles of potential biological importance, we report here a facile one-pot selective synthesis of the title compounds via reaction of 4-benzoyl-1- cyanoacetylthiosemicarbazide (1) with -halocar- bonyl compounds and ethyl iodide.  Corresponding author. E-mail: Bondock@mans.edu.eg