Microwave-accelerated Synthesis Of Novel Thiocarbohydrazide Derivatives

Microwave irradiation as an efficient thermal energy source has become a standard technique in various fields of chemistry, especially in organic chemistry. Synthesis of chemical compounds which normally require long reflux time can be achieved conveniently and very rapidly in a microwave oven. Compared to the classical heating methods, microwave irradiation has the advantages of short reaction time, high yields, pure products and easy workup. The use of microwave energy to activate organic reactions has been taking a new dimension very recently.Thiocarbohydrazide derivatives are widely used in medicinal research, analytical chemistry and so on. Furthermore, thiocarbohydrazide and its derivatives are important intermediates in organic synthesis. In addition, acylthiosemicarbazides, 1,3,4-thiadiazoles, 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles have extensive biological activities. Therefore they have also been applied to many fields, for instance, medicine, agronomy, biology, etc.In this thesis, thiocarbohydrazide derivatives, 1, 5-diacyl thiocarbohydrazides were first eco-friendly synthesized using phase transfer catalyst. Then, a series of new compounds and their heterocyclic derivatives were further synthesized using thiocarbohydrazide or 1, 5-diacyl thiocarbohydrazides as intermediates. In all of these new compounds, active groups such as acylthiosemicarbazide, 1,3, 4-thiadiazole, 1, 2, 4-triazolo[3,4-b]-1,3,4-thiadiazole are included respectively. The structures of all compounds were confirmed by IR, ~1H NMR, MS and elemental analysis. The experimental methodologies, results and possible mechanism were also proposed in this thesis.This thesis includes five chapters:Chapter 1: Introduction.In the beginning, synthesis of thiocarbohydrazide was introduced briefly. And then, the properties of thiocarbohydrazide and its applications in chemical synthesis and industry were introduced. Finally, the applied progress of MWI in chemistry synthesis was summarized simply.Chapter 2: Synthesis of 1, 5-bis(aroyIcarbamothioyI)thiocarbohydrazides. Eleven new 1, 5-bis(aroylcarbamothioyl)thiocarbohydrazides were synthesized at room temperature under phase transfer catalysis condition in high yield by two-step reactions: a variety of aroyl chlorides first reacted with ammonium thiocyanate, then with thiocarbohydrazide. The structures of all compounds were confirmed by IR, ~1H NMR, MS and elemental analyses.Chapter 3: Microwave-promoted Synthesis of 2-aryl-5-acylhydrazino-1, 3, 4-thiadiazoles.Thiocarbohydrazide readily reacted with a variety of aroyl chlorides at room temperature under phase transfer catalysis condition to afford ten 1, 5-diaroylthiocarbohydrazides in high yield. Furthermore, A concise and rapid synthetic route to 2-aryl-5-acylhydrazino-l,3,4-thiadiazoles by the cyclization of 1,5-diaroylthiocarbohydrazides under microwave irradiation is described, and the structures of all compounds were confirmed by IR, ~1H NMR, MS and elemental analyses. This strategy has features of mild condition, short reaction period, and simple work-up procedure.Chapter 4: Microwave-promoted Synthesis of 3, 6-disubstituted-1, 2, 4-triazolo[3,4-b]-1,3,4-thiadiazoles.A series of 3, 6-disubstituted-1, 2, 4-triazolo[3,4-b]-1,3,4-thiadiazoles was synthesized under microwave irradiation by one-step reaction: substituted benzoic acid directly reacted with thiocarbohydrazide using silica supported dichlorophosphate as dehydrating agent. The structures of all compounds were confirmed by IR, ~1H NMR, MS and elemental analyses. Compared to the traditional method, this strategy has features of short reaction period, benign to environment and simple work-up procedure.Chapter 5: Rapid microwave-promoted synthesis of l-arylidene-2-(5-aryl-1, 3,4-thiadiazol- 2-yl)hydrazines.Eleven new 1-arylidene-2-(5-aryl-1, 3, 4-thiadiazol-2-yl)hydrazines were synthesized under microwave irradiation using silica supported dichlorophosphate as dehydrating agent. The structures of all compounds were confirmed by IR, ~1H NMR, MS and elemental analyses.