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7a-Aniinophenylacetamido-~3-cephalosporin esters cyclize to 3-dihydrothiazinyl-6-phenylpiperazine-2,5-diones by an intramolecular nucleophilic attack of the side-chain a-amino-function while under the same conditions the analogous Ga-aminophenylacetamidopenicillin ester does not cyclize, because of steric hindrance to intramolecular attack.THE a-aminophenylacetamido-/3-lactam compounds cephalexin (la), cephaloglycin (lb), and ampicillin (5a) are clinically useful broad spectrum antibiotics, effective orally against both Gram-positive and Grani-negative bacteria. The p-lactam part of penicillins and cephalosporins is readily susceptible to attack by a variety of nucleophiles. The penicillins ring-open to penicilloic acids1 (esters, amides, or polymers) ,2 while the cephalosporins form the analogous unstable "cephalosporoates" which rapidly fragment in aqueous s o l ~t i o n . ~tThe intramolecular nucleophilic attack of a side chain a-amino-function has not been demonstrated but was suggested as a decomposition mechanism for cephaloglycin by Hoover and Stedniad and for ampicillin by Jusko.6 We now report results that demonstrate intramolecular nucleophilic attack of the a-aminophenylacetamido-side chain on cephalexin trichloroethyl (lc) and p-nitrobenzyl (Id) esters and cephaloglycin lactone (3). The analogous reaction does not occur with the corresponding penicillin system, i.e. ampicillin trichloroethyl ester (5b).zCompounds (2a) (decomp. 179"), (2b) (decomp. 165"), and (4) (decomp. 145') were obtained by heating the corresponding @-lactams in dilute benzene under reflux overnight and recovering the resulting crystalline piperazinediones by filtration. The yields ranged from 10-49%.

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Beim Erwärmen der β‐Lactame (I) und (III) in siedendem Benzol erhält man durch einen intramolekularen nucleophilen Angriff die Piperazin‐dione (II) bzw. (IV).