Some 5-unsubstituted acetylenic and vinylic 1,2,4-oxadiazoles

Abstract

3-trans-Styryl-l.2.4-oxadiazoles(2) have been prepared by treating unsaturated amide oximes with trialkyl orthoformates or dimethylformamide dimethyl acetal, and from 1,2,4-oxadiazol-3-ylmethylene(triphenyl)phosphonium chloride (1 2). Phenylpropiolamide oxime with formyl fluoride gives 3-phenylethynyl-1.2.4-oxadiazole which, on nitration, gives as the main product 3-p-nitrophenylethynyl-l.2.4-oxadiazole (4; R = NO2). This compound has been converted into (4 ; R = CI). p-Chlorophenylpropiolonitrile gives only 3-amino-5-p-chlorophenylisoxazole (1 5) when treated with hydroxylamine. trans-3-(2-and -3-Thienyl)acrylonitrile react more readily with hydroxylamine than do the cis-acrylonitriles. Some cis-3-styryl-l.2.4-oxadiazoles have been obtained from the corresponding trans-compounds by photoisomerization.IT has been reportedl~2 that many 3-substituted 1,2,4oxadiazoles, particularly 3-$-chlorophenyl-l,2,4-oxadiazole, are effective against helminths in small animals. The high anthelminthic activity reported for ' Pyrantel ' (1) led us to prepare some 3-styryl-1,2,4-oxadiazoles (2) Me(and similar compounds with heterocyclic groups attached to vinyl side-chains), some related 4,5-dihydro-1,2,4-0xadiazoles (3), and some 3-arylethynyl-l,2,4o xadiazoles (4).Of the compounds in the Table, some were made by treating the appropriate amide oxirnes with triethyl or trimethyl orthoformate in the presence of boron trifluoride? and some by the Wittig reaction (see below) from the phosphorane (5). Several other compounds were made by the reduction of appropriate nitrocompounds, with subsequent Sandmeyer reactions.We first obtained 9-methylthiocinnarnonitrile (6) by the Meerwein reaction; diazotized P-methylthioaniline reacted with acrylonitrile to give the expected chloronitrile, which was dehydrochlorinated by triethylamine, but the overall yield seldom exceeded 4y0, and o-and wt-methylthioaniline gave even lower yields. However, p-methylsulphinylaniline, prepared by oxidizing pinethylthioaniline with hydrogen peroxide in acetone (a procedure reported' t o be hazardous), or, better, in methylene chloride, gave the nitrile (7) in 25% overall yield from the amine, and we obtained from (7) the corresponding amide oxime (see Scheme 1). This amide osime did not react readily with formyl fluoride. It was decomposed by triethyl orthoformate, but it gave the oxadiazole (2; R = p-MeSO*C6H4) when treated with dimethylformamide dimethylacetal (see later). Reduction of the nitrile (7) with titanium(Ir1) chloride gave

Pentafluorobenzaldehyde and its utilizing in organic synthesis

“…In the reaction of the PFBA with 2,3,4-methylene-oxadiazolyltriphenylphosphorane (52) is formed pentafluorostyrene (53), which is substituted with heterocycle (Scheme 34 [306]). …”

“…The Wittig reactions of pentafluorobenzaldehyde were researched widely [274,[305][306][307][308][309][310][311][312][313][314][315][316][317][318][319]. The PFBA reacts easily with fluoromethylene triphenylphosphorane (50) in toluene and this reaction gives (E)-, (Z)-isomer fluorovinyl benzene (51a, 51b, Scheme 33 [305]).…”

Design and Synthesis of N1,N5-bis[4-(5-Alkyl-1,2,4-oxadiazol-3-yl)phenyl]glutaramides as Potential Antifungal Prodrugs

“…General synthesis oxadiazoles involve the transformation of an amidoxime into an O -acyl- amidoxime by the reaction of an acid chloride [25], anhydride [26], ester [27] or an orthoester [28]. The O -acylamidoxime undergoes cyclization under the influence of a strong base [29] or by heating to 85 °C in 2-methoxyethyl ether [30] or by heating the sample slightly above its melting point [31].…”

ChemInform Abstract: New NO Donors with Antithrombotic and Vasodilating Activities. Part 26. Amidoximes and Their Prodrugs.

“…Compound 2a was purchased from Aldrich. The synthesis of 2b [8] , 2c [9], 2d [10] , 2e [11] , 2f [12] , 2g [13] , 2h [14] , 2i [15] , 2j [16] , 2l [17] , 2m [18] , 2o [19] , 2p [20] , 2q [21] , 3e [22] , 3f [12] , 3j [23] , 4e [22] and 4j [23] already has been reported.…”

“…From 7.81 g (50 mmol) 3-indolylmethane carbonitrile by the method of Claisse et al [17] . Beige neddles (methanol/chloroform), mp 143 °C, yield 3.79 g (40%).…”