Study On The Synthesis Of 2-Amino-5-aryloxymethylene-1, 3, 4-thiadiazole And Its Derivatives Under Microwave Irradiation

During the last two decades years, microwave irradiation as an efficient thermal energy source has become a standard technique in various fields of chemistry, especially in the application 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.The typical organic synthesis has long been carried out in organic solvents because reactions in solvents proceed homogeneously and exchange energy smoothly. However, most of organic solvents are volatile, flammable, toxic and unrecoverable. In order to prevent environmental pollution, in the most recent years, chemists have begun investigating the possibility of using water as solvent for organic reactions. The use of water as a medium in organic reaction has received considerable attention due to its several advantages, for example, it is the cheapest solvent available on earth, avoiding extensive drying of reactants, catalysts and solvents, non-hazardous to the environment and isolation of the organic products can be performed simply by phase separation. To use water as reaction media is also beneficial to reaction rates and selectivity of important organic transformations. Moreover, solvent-free reactions avoiding the use of organic solvents, are clean, effective and economical, in which the safety is largely increased, workup procedure is considerably simplified and the cost is greatly reduced. Therefore, solvent-free organic reactions have attracted many interests in chemical industry. Indeed, most of solvent-free organic reactions occur in solid state, the tightly and regularly arranged structures of solids make the reactions proceed more efficiently and selectively than solution ones. Furthermore, due to the simplicity in process and handling, solvent-free reactions can be accelerated by means of grinding, microwave irradiation and ultrasonic irradiation.2-Amino-1,3,4-thiadiazole and their derivatives have extensive biological activities, such as antibacterial, anticancer, antitubercular, antihypertension and herbicidal activities. Therefore they have been applied to many fields, for instance, medicine, agronomy, biology and so on. In this thesis, we designed and synthesized three series of thiadiazole derivatives from 2-amino-5-aryloxymethylene-1,3,4-thiadiazole under microwave irradiation. It is expected that synthesis of the aimed products which have more efficient biological activities under mild condition from commercially available materials and expand the application of microwave irradiation in aqueous media or solvent-free organic synthesis.The thesis includes seven chapters:Chapter one: This part covered the new advance of eco-friendly synthesis of heterocyclic compounds under microwave irradiation under solvent-free condition and the reactions in aqueous media under microwave irradiation, we also reviewed the new compounds of imidazo[2,1-b]-1,3,4-thiadiazole and their pharmacological activities reported in recent years.Chapter two: A series of 2-aryloxymethylene-6-arylimidazo[2,1-b]-1,3,4-thiadiazoles were synthesized by condensation reaction of2-amino-5-aryloxymethylene-1,3,4-thiadiazole withω-bromoacetophenone in ethanol solvent under microwave irradiation without any catalyst. We also studied the different affects of varies conditions (ratios, solvent, irradiation power and time) on the reaction and afforded 36 new compounds of 2,6-disubstituted imidazo[2,1-b]-1,3,4-thiadiazoles.Chapter three: We studied the method for the synthesis of 2-aryloxymethylene-6-arylimidazo-[2,1-b]-1,3,4-thiadiazole in aqueous media under microwave irradiation.Chapter four: We studied the method for the synthesis of 2-aryloxymethylene-6-arylimidazo-[2,1-b]-1,3,4-thiadiazole under microwave irradiation in solvent-free condition.Chapter five: N,N'-Disubstituted ureas have extensive biological and physiological activities. Therefore they have been applied to many fields, for instance, medicine, agronomy, biology and so on. The new synthesis methods and their pharmacological activities of these compounds are reviewed in this chapter.Chapter six: Under microwave irradiation conditions via one-pot procedure, the reaction of 2-Amino-5-aryloxymethylene-l,3,4-thiadiazoles with N-substituted trihaloacetamides in the presence of powder NaOH in DMSO solvent afforded 13 new N-(5-aryloxymethylene-1,3,4-thiadiazole-2-yl)-iV'-arylureas in excellent yields. We also studied the different affects of varies conditions (ratios, solvent, irradiation power and time) on the reaction.Chapter seven: An efficient one-pot condensation method for the preparation of 5-alkyl-1-(5-aryloxymethylene-1,3,4-thiadiazole-2-yl)-3-aryl-1,3,5-triazine-2-ones isdescribed. The synthesis was based on a Mannich condensation among readily available starting materials N,N′-disubstituted ureas, aqueous formaldehyde and primary amines in aqueous media under microwave irradiation and afforded 16 new compounds in excellent yields. We also studied the affects of varies conditions (ratios, solvent, irradiation power and time) on the reaction.The structures of all the compounds were confirmed by elemental analyses, IR and ~1H NMR and 13C NMR.