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Cephalosporin C (I), the amine (11), and derived cephalosporanic acids (111; R1 = H) are converted into new derivatives by replacing the acetoxygroup with various sulphur, nitrogen, and carbon nucleophiles.7-Aminocephalosporanic acid ( 11) is produced by the action of thiourea on 7-chloroacetamidocephalosporanic acid or spontaneously from 4'-chlorobutanamido-or 5'-chloropentanamidocephalosporanic acids as a result of intramolecular displacement.CONVERSION of the antibiotic cephalosporin C (I) into 7-aminocephalosporanic acid (11) and subsequent acylation to give a series of 7-acylaminocephalosporanic acids (111 ; R1 = H) have been de~cribed.l-~ We have converted such acids into their methyl esters (111; R1 = Me), lactones (IV), and I-oxides (VIII; Y = OAC).~ The stereochemistry of the oxides has not been studied. Hale, Newton, and Abraham described 5 the transformation of cephalosporin C (I) into the pyridinium betaine (VI; X = C,H5N+) and showed that a range of substituted pyridines formed similar derivatives (C, compounds) by replacing the acetoxy-group. The formation of a Bunte salt ( I X ; Y = S,O,Na R = [CH,],*CH(NH,)*CO,H), when cephalosporin C is treated with sodium thiosulphate was proposed 6 to account for the resulting increase in antibacterial activity. We have studied the substitution of the acetoxy-group in salts of 7-acylaminocephalosporanic acids (I11 ; R1 = H) by azide, NN-dimethyldithiocarbamate, thiobenzoate, and

The combined action of bases and acid anhydrides on 7-acylamidocephalosporanic acids, and the action of bases on their esters, set up equilibria in which the corresponding A2-isomers predominate. The isomerisation represents a prototropic shift probably favoured by the sulphur atom in the dihydrothiazine ring. The acetoxy-group in the A2-compounds can be replaced by nucleophiles.Treatment of methyl 3-acetoxymethyl-7~-phenylacetamidoceph-3-em-4-carboxylate 1 [-oxide with a base res u I ts i n d eca rboxy I a t i o n . Attempts to prepare 7 pp he n y I a ceta m i d o ce p h -2 -em -45car boxy I i c acid 1 toxi d e resulted in formation of its A3-isomer and some carbon dioxide.

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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