Abstract: 1-[.alpha.-(Carboxy)-4-hydroxybenzyl]-3.beta.-aminoazetidin-2-one esters are prepared by converting 2-acyl-3,3-dialkyl-7-oxo-.alpha.-[4-(benzyloxy)phenyl]-4-thia-2,6-diazabic yclo[3.2.0]-heptane-6-acetic acid esters with mercuric acetate in an aqueous organic solvent mixture, e.g., in aqueous methanol, to 7-oxo-3-phenyl-.alpha.-[4-benzyloxy)phenyl]-4-oxa-2,6-diazabicyclo[3.2.0]h ept-2-ene-1-acetic acid esters and the latter are reacted with PCl.sub.5 and pyridine to provide the monocyclic 1-[.alpha.-(carboxy)-4-benzyloxybenzyl]-3.beta.-(.alpha.-chlorobenzylidene amino)-4-chloroazetidin-2-one esters. Reduction of the dichloro azetidin-2-one with an organo tin hydride and azobisisobutyronitrile affords the deschloro, 1-[.alpha.-(carboxy)-4-benzyloxybenzyl]-3.beta.-benzylideneaminoazetidin-2 -one ester. The latter is hydrolyzed and the 4-benzyloxy group is cleaved via catalytic hydrogenolysis to yield an ester of 1-[.alpha.-(carboxy)-4-hydroxybenzyl]-3.beta.-aminoazetidin-2-one. The 3.beta.

Abstract: Process for 1-[.alpha.-(carboxy)-4-hydroxy or protected-hydroxybenzyl]-3-acylamidoazetidin-2-one esters, useful intermediates for preparing antibiotic FR 1923, comprising the ring opening of a 2-acyl-3,3-dialkyl-7-oxo-.alpha.-[4-(protected-hydroxyphenyl]-4-thia-2,6-d iazabicyclo[3.2.0]heptane-6-acetic acid, ester sulfoxide with a sulfonic acid and heat to provide a 3-acylamido-4-(2-oxaalkylthio)azetidin-2-one ester which on treatment with sulfuryl chloride affords a reaction product mixture that is then reduced with an organo tin hydride, e.g., tri(n-butyl)tin hydride, to the product. N-Deacylation of the 3-acylamido group followed by acylation with the 3-acyl portion of FR 1923, deblocking of the amino-protecting group and deesterification affords FR 1923.

Abstract: Monocyclic .beta.-lactam antibiotics of the formula ##STR1## WHEREIN R is amino or acylamino, e.g., phenylacetylamino, phenylglycylamino and 2-[4-(3-amino-3-carboxypropoxy)phenyl]-2-hydroximinoacetylamino; R.sub.1 is H or ester forming group; R.sub.2 is H, --OCH.sub.3, --SCH.sub.3, or --CH.sub.3 ; and R.sub.3 is H or acetoxy; are useful antibacterials for controlling .beta.-lactamase producing gram-negative bacteria and other pathogens. Intermediates useful in the preparation of the antibiotics and a novel process for preparing 4.alpha.-acetoxy substituted azetidin-2-ones are provided.

Abstract: 1-[.alpha.-(Carboxy)-4-hydroxybenzyl]-3.beta.-aminoazetidin-2-one esters are prepared by converting 2-acyl-3,3-dialkyl-7-oxo-.alpha.-[4-(benzyloxy)phenyl]-4-thia-2,6-diazabic yclo[3.2.0]-heptane-6-acetic acid esters with mercuric acetate in an aqueous organic solvent mixture, e.g., in aqueous methanol, to 7-oxo-3-phenyl-.alpha.-[4-(benzyloxy)phenyl]-4-oxa-2,6-diazabicyclo[3.2.0] hept-2-ene-1-acetic acid esters and the latter are reacted with PCl.sub.5 and pyridine to provide the monocyclic 1-[.alpha.-(carboxy)-4-benzyloxybenzyl]-3.beta.-(.alpha.-chlorobenzylidene amino)-4-chloroazetidin-2-one esters. Reduction of the dichloro azetidin-2-one with an organo tin hydride and azobisisobutyronitrile affords the deschloro, 1-[.alpha.-(carboxy)-4-benzyloxybenzyl]-3.beta.-benzylideneaminoazetidin-2 -one ester. The latter is hydrolyzed and the 4-benzyloxy group is cleaved via catalytic hydrogenolysis to yield an ester of 1-[.alpha.-(carboxy)-4-hydroxybenzyl]-3.beta.-aminoazetidin-2-one. The 3.beta.

Abstract: 7-Alkoxy-3-bromomethyl-3-cephems are provided by reacting a 3-methylenecepham with an alkali metal salt of a lower primary alcohol in the presence of a positive brominating agent at a temperature ranging from about -80.degree. to about 0.degree. C. The 3-bromomethylcephems provided by this invention are useful intermediates for the preparation of known cephalosporin antibiotics.

Abstract: 7-Alkoxy-3-chloromethyl-3-cephems are provided by reacting a 3-methylenecepham with an alkali metal salt of a lower primary alcohol in the presence of tert-butyl hypochlorite at a temperature ranging from about -80.degree. to about 0.degree. C. The 3-chloromethylcephems provided by this invention are useful intermediates for the preparation of known cephalosporin antibiotics.

Abstract: Reaction of 3-hydroxy cephalosporins with alkylfluorosulfonates in the presence of a base provides 3-alkoxy cephalosporins which are useful as intermediates for cephalosporin antibiotic preparation.

Abstract: 6-Alkoxylated-6-acylamidopenicillanic acids and 7-alkoxylated-7-acylamidocephalosporin acids and esters thereof, are provided by reacting a 6-acylamidopenicillanic acid ester or a 7-acylamidocephalosporin ester under anhydrous conditions at -90.degree. C. to -15.degree. C. with an alkali metal salt of a lower alkyl alcohol in the presence of an excess of the corresponding alcohol to produce, in situ, the anionic form of the antibiotic which on halogenation with a positive halogen compound, e.g. t-butyl hypochlorite, yields the compound of the invention. Compounds of the invention, e.g. 6-methoxy-6-phenoxy-acetamidopenicillanic acid and 7-methoxy-7-[2-(2-thienyl)acetamido]cephalosporanic acid are useful antibiotics.

Abstract: 3-Halomethyl-3-cephems are provided by reacting a 3-methylenecepham with an alkali metal salt of a lower alcohol or a bicyclic amidine base in the presence of a positive halogenating agent at a temperature ranging from -80.degree. to about 20.degree. C. The 3-halomethylcephems provided by this invention are useful intermediates for the preparation of known cephalosporin antibiotics.

Abstract: 3-Hydroxymethyl-2-cephems are provided by (1) reacting a 2-halomethylcephem compound with a .gamma.-hydroxycarboxylic acid salt or a .delta.-hydroxycarboxylic acid salt and (2) reacting the novel .gamma. or .delta.-hydroxy esters thereby obtained with a protic acid. The 3-hydroxymethylcephems provided by the process of this invention are useful intermediates for the preparation of known cephalosporin antibiotics.

Abstract: A 3-exomethylenecepham sulfoxide ester is reacted with a mixture of a carboxylic acid of the formula ##STR1## and the corresponding anhydride of said carboxylic acid at a temperature of from about 70.degree. C. to about 130.degree. C. to produce the corresponding 3-acyloxymethyl-.DELTA..sup.2 -cephem. This product is useful as an intermediate in the preparation of antibiotically active cephalosporins.

Abstract: 6-acylamido-6-methoxypenicillanic acids are obtained by reacting a 6-acylamidopenicillanic acid with mercuric acetate in methanol to yield a methyl .alpha.-methoxypenicilloate. Esterification of the latter with isobutylene affords the methyl, t-butyl diester of the methoxypenicilloic acid which undergoes selective hydrolysis in base to provide the free .alpha.-carboxylic acid half t-butyl ester of the penicilloic acid. The latter on reaction with dicyclohexylcarbodiimide affords an oxazolone-thiazolidine of the formula ##STR1## WHICH WITH 98% FORMIC ACID PROVIDES A COMPOUND OF THE INVENTION.

Abstract: 3-Hydroxycephalosporins are prepared by treating a 3-hydroxy-4-bromo-2-(2-formylthio-4-oxo-3-amido or imido-1-azetidinyl)-2-butenoate ester with mercuric acetate and contacting the resulting reaction mixture with a mercuric ion precipitator.

Abstract: 6-Alkoxylated-6-acylamidopenicillanic acids and 7-alkoxylated-7-acylamidocephalosporin acids and esters thereof, are provided by reacting a 6-acylamidopenicillanic acid ester or a 7-acylamidocephalosporin ester under anhydrous conditions at -90.degree. C. to -15.degree. C. with an alkali metal salt of a lower alkyl alcohol in the presence of an excess of the corresponding alcohol to produce, in situ, the anionic form of the antibiotic which on halogenation with a positive halogen compound, e.g. t-butyl hypochlorite, yields the compound of the invention. Compounds of the invention, e.g. 6-methoxy-6-phenoxyacetamidopenicillanic acid and 7-methoxy-7-[2-(2-thienyl)acetamido]cephalosporanic acid are useful antibiotics.

Abstract: 7-Acylamido-3-cephem-4-carboxylic acid antibiotics directly substituted in the 3-position of the cephem ring system with a sulfur atom bonded to a 5- or 6-membered heterocyclic ring, a lower alkyl group, or a phenyl or substituted phenyl group are prepared with the corresponding 3-halo-3-cephem esters. For example, p-nitrobenzyl 7-[2-(2-thienyl)acetamido]-3-chloro-3-cephem-4-carboxylate reacts with 1-methyl-1H-tetrazol-5-ylthiol to provide p-nitrobenzyl 7-[2-(2-thienyl)acetamido]-3-[(1-methyl-1H-tetrazol-5-yl)thio]-3-cephem-4- carboxylate. The p-nitrobenzyl ester group is removed by catalytic hydrogenolysis to provide the antibiotic carboxylic acid compound. Alternatively, the antibiotics are prepared by reacting a 3-alkylsulfonyloxy, or 3-arylsulfonyloxy-3-cephem, for example, 3-methanesulfonyloxy-3-cephem, or a 3-p-toluenesulfonyloxy-3-cephem with the heterocyclic thiol, the phenyl or substituted phenylthiol, or with the lower alkylthiol.

Abstract: 7.beta.-acylamido-7.alpha.-methoxycephalosporin compounds in which the acylamido group has the formula ##SPC1##In which R is carboxy, protected carboxy, phosphono, protected phosphono, sulfo, or protected sulfo. The compounds exhibit antibiotic activity, in particular against Pseudomonas and Serratia type microorganisms.

Abstract: Reaction of 3-hydroxy cephalosporins with alkylfluorosulfonates in the presence of a base provides 3-alkoxy cephalosporins which are useful as intermediates for cephalosporin antibiotic preparation.