Preparation and reactions of 3-[3-(aryl)-1,2,4-oxadiazol-5-yl]: propionic acids

Journal of the Brazilian Chemical Society

Srivastava, R.M¹  Universidade Federal de Pernambuco, Recife, Brazil¹  Seabra, G.M¹ 

关键词: arylamidoximes;    bis-1;    2;    4-oxadiazoles;    diaryl-1;    2;    4-oxadiazoles;    ab-initio sto-3g calculations     Introduction Although the synthesis of acids 3a-g have been described;    their yields were rather low2-4. In an attempt to improve the yields of these acids;    we discovered that heating a mixture of arylamidoximes 1a-f and succinic anhydride 2 in a domestic microwave oven for 10 min provides 3a-f in high yield (Scheme 1). These acids are important because 3-[3-(phenyl)-1;    2;    4-oxadiazol-5-yl] propionic acid (3a) has been found to possess significant peripheral analgesic and anti-inflammatory properties5. Compounds 3b-e;    in a preliminary screening;    showed some analgesic property;    in fact;    3b and 3d have slightly better activity than dipyrone. Acid 3b also showed anti-inflammatory property but 30 percent less than indomethacine6. During the preparation of 3a-g;    we carefully investigated two minor products and identified them as 4a-f and 5a-f respectively. We synthesised 4a-f from 3a-f in order to verify their identities. The literature reports the synthesis of only 4a;    from benzamidoxime and succinic anhydride7;    and its spectroscopic properties8;    9. Besides this;    no more information was available on this class of compounds. Next we transformed acids;    3a-g to their methyl esters;    6a-g. None of the methyl esters were known. Therefore;    this paper describes the improved synthesis of 3a-f and the preparations of 4a-f from 3a-f;    and of 6a-g from 3a-g;    respectively.   Results and Discussion The reaction of arylamidoximes 1a-f with succinic anhydride 2 was reported to yield 3a-f in poor to moderate yields4. Repeating this method under improved conditions and examining the products carefully by thin layer chromatography (TLC);    we detected two fast running minor components. Their separation was achieved on a silica gel column. The products were identified as 3a-f (Rf = 0;    1);    4a-f (Rf = 0;    5) and 5a-f (Rf = 0;    8) respectively. Acids 3a-f were the major products (70-75%) whereas 4a-f and 5a-f were the minor ones. If the quantities of all three products are summed up;    a yield of 85% was obtained. Table 1 lists the yields of 3a-f obtained by heating 1 and 2 in a preheated oil bath (GPA);    in dioxane (GPB) or in a microwave oven (GPC). ;   

DOI  :  10.1590/S0103-50531997000400013

学科分类：化学（综合）

来源: SciELO

【 摘 要 】

Although the synthesis of acids 3a-g have been described, their yields were rather low2-4. In an attempt to improve the yields of these acids, we discovered that heating a mixture of arylamidoximes 1a-f and succinic anhydride 2 in a domestic microwave oven for 10 min provides 3a-f in high yield (Scheme 1). These acids are important because 3-[3-(phenyl)-1,2,4-oxadiazol-5-yl] propionic acid (3a) has been found to possess significant peripheral analgesic and anti-inflammatory properties5. Compounds 3b-e, in a preliminary screening, showed some analgesic property; in fact, 3b and 3d have slightly better activity than dipyrone. Acid 3b also showed anti-inflammatory property but 30 percent less than indomethacine6. During the preparation of 3a-g, we carefully investigated two minor products and identified them as 4a-f and 5a-f respectively. We synthesised 4a-f from 3a-f in order to verify their identities. The literature reports the synthesis of only 4a, from benzamidoxime and succinic anhydride7, and its spectroscopic properties8,9. Besides this, no more information was available on this class of compounds. Next we transformed acids, 3a-g to their methyl esters, 6a-g. None of the methyl esters were known. Therefore, this paper describes the improved synthesis of 3a-f and the preparations of 4a-f from 3a-f, and of 6a-g from 3a-g, respectively.   Results and Discussion The reaction of arylamidoximes 1a-f with succinic anhydride 2 was reported to yield 3a-f in poor to moderate yields4. Repeating this method under improved conditions and examining the products carefully by thin layer chromatography (TLC), we detected two fast running minor components. Their separation was achieved on a silica gel column. The products were identified as 3a-f (Rf = 0,1), 4a-f (Rf = 0,5) and 5a-f (Rf = 0,8) respectively. Acids 3a-f were the major products (70-75%) whereas 4a-f and 5a-f were the minor ones. If the quantities of all three products are summed up, a yield of 85% was obtained. Table 1 lists the yields of 3a-f obtained by heating 1 and 2 in a preheated oil bath (GPA), in dioxane (GPB) or in a microwave oven (GPC).   The yields of acids 3a-f have been slightly improved by refluxing the arylamidoxime and succinic anhydride in dioxane (GPB). This experiment also gave the two minor products. Another fast and efficient synthesis of 3a-f was found. When an intimate mixture of an appropriate arylamidoxime and succinic anhydride was heated in a domestic microwave oven (80% potency) for 10 min (GPC), compound 3 was obtained as the major product and 4 and 5 as the minor products. Separation by column chromatography provided pure acids in high yields except in the

【 授权许可】

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