Synthesis And Study Of The Derivatives Of 2-Benzo[b]furan Carboxylic Acid Under Microwave Irradiation

Thiosemicarbazides and their cyclic derivatives have extensive biological activities, such as antibactery, antihypertension, anticonvulsive, antidepressant, fugicide, insecticide, herbicide and plant growth regulator activities. Therefore they have been applied to many fields, for instance, medicine, agronomy, biology, etc. Substituted 1,3,4-oxadiazoles have been of great interest to the medicinal chemists for many years because of their antimicrobial, antimitotic, antiinflammatory, psychotropic, antiaflatoxigenic, and anticonvulsant activities. In addition, 1,2,4-triazolo [3,4-6] [1,3,4] thiadiazole or 1,2,4-triazolo [3,4-6] [ 1,3,4] thiadiazine derivatives have represented an interesting class of compounds possessing a wide spectrum of biological activities, since they combined two bioactive sub-structure, 1,2,4-triazole and 1,3,4-thiadiazole (or thiadiazine). Meanwhile, benzo[6]furan derivatives are of interest because of their frequent occurrence in nature and their wide range of biological effects.To our best knowledge, there are few literatures that reported the synthesis of the compounds containing 2-benzo[b]furan and thiourea, thiadiazole or oxadiazole.In this thesis, we designed and synthesized 68 heteroatom compounds fused 2-benzo[b]furan of three series derived from 2-benzo[b]furan carboxylic acid, under the condition of phase transfer catalyst, microwave irradiation or under the condition of solid state.Series I: Microwave-promoted synthesis of l-aroyl-4-[2 -benzo(b)furan-carbonyl] -thiosemicarbazides and their cyclic derivatives. 7 New l-aroyl-4-[2 -benzo(b)furancar-bonyl]-thiosemicarbazides were synthesized by the reactions of 2-benzofurancabonyl chloride with ammonium thiocyanate and arylcarboxylic acid hydrazides under phase transfer catalysis and microwave irradiation. Treatment of the resulting thiosemicarbazides with potassium iodate, acetic acid and mercuric acetate, under microwave irradiation gaves 7 l-aroyl-4-[2 -benzo(b)furancarbonyl]-semicarbazides, 7 new 2-aryl-5-[2-benzo(b)furancarboxamide]-1,3,4-thiadiazoles and 6 new2-aryl-5-[2 -benzo(b)furancarboxamide]-l,3,4-oxadiazoles in high yields, respectively. And we also achieved the transformation of the C=S in l-aroyl-4-[2 -benzo(b)furan-carbonyl]-thiosemicarbazides into C=O by HIO4 2H2O.Series II: Microwave-accelerated one-step synthesis of 2-aroyl/aryloxymethylene -5-[2 -benzo(b)furyl]-l,3,4-oxadiazole. Therefore 2-benzo(b)furancarboxylic acid react with equivalent of arylhydrazines and aryloxyacetyl hydrazines, respectively, in the presence of phosphorus oxychloride under microwave irradiation to afford 18 compounds of 2,5-disubstituted 1,3,4-oxadiazoles in good to high yield.Series III: Synthesis of 4-amino-3-[2 -benzo(b)furyl]-5-mercapto-s-triazole and its derivatives. The key synthon 4-amino-3-[2 -benzo(b)furyl]-5-mercapto-s-triazole was prepared by two-step reaction derived from 2-benzofurancarboxylic acid hydrazide under microwave irradiation. The reactions of 4-amino-3-[2 -benzo(b)furyl]-5-mercapto-s-triazole with arylcarboxylic acid, aryloxyacetic acid and w-bromo-acetophenone to afford 12 new 6-aryl-3-[2 -benzo(b)furyl]-s-triazolo[3,4,-b]-l,3,4-thiadiazoles, 8 new 6-aryloxy-methylene-3-[2 -benzo(b)furyl]-s-triazolo[3,4-b]-l,3,4-thiadiazoles and 3 new 6-aryl-3-[2 -benzo(b)furyl]-s-triazolo[3,4-b]-l,3,4-thiadiazines, are researched, respectively. Considerable increase in reaction rate has been observed with improved yields under microwave irradiation.The structures of all the compounds were conformed by Elemental Analysis, IR and 1H NMR.