1,2,4-oxadiazóis: síntese, desenvolvimento denovas metodologias sintéticas e avaliação daatividade antiinflamatória
This work describes the obtainment of many novel 3,5-disubstituted 1,2,4-oxadiazoles. First,the synthesis of ten previously unknown 3-aryl-5-tridecyl- and 3-aryl-5-heptadecyl-1,2,4-oxadiazoles 40a-g, 40h-j, starting from arylamidoximes 12a-g and tetradecanoic as well asheptadecanoic acids 38a and 38b is reported. Second, seven new 3-aryl-5-(cis-heptadec-13-ene)-1,2,4-oxadiazoles 43a-g derived from arylamidoximes (12a-f,h) and oleic acid (oroleolyl chloride) have been prepared employing conventional and microwave irradiationmethodologies. Molecular orbital calculations of heterocycles 43a-g using semi-empirical andab initio (HF/6-31G) methods gave interesting information regarding the geometry andmolecular conformation of these molecules. Third, the reaction of arylamidoximes (12a,c-f,h)and propioloyl chloride (44) unexpectedly furnished bis-aryl-1,2,4-oxadiazoles (47a-g). Themechanism of formation of these compounds is suggested for the first time. Fourth, anunusual production of 3-aryl-5-methyl-1,2,4-oxadiazoles (64a-g from arylamidoximes (12af,h) and 2,3-butanedione (57) has also been unravelled in the present work. Next, newmethodologies for the synthesis of 1,2,4-oxadiazoles using either mesyl chloride or ethylchloroformate with acids (38d-j) and arylamidoximes (12a,d,h), in an one pot procedure,were described herein. All the above-mentioned syntheses gave good to excellent yields ofoxadiazoles. Finally, antiinflamatory property of compounds 40b-d has been evaluated usingthe acute peritonitis procedure. All these oxadiazoles caused 40-52% inflammation reductionin mice.
Advisor:Rajendra Mohan Srivastava
School:Universidade Federal de Pernambuco
Source Type:Master's Thesis
1,2,4-oxadiazoles, fatty acids, acyl chlorides, 2,3-butanedione, antiinflammatoryactivity
Date of Publication:09/26/2007