GB1291850A - Process for preparing penicillin derivatives - Google Patents

Abstract

1291850 Amino-penicillin arylsulphonates AMERICAN HOME PRODUCTS CORP 24 Dec 1969 [24 Dec 1968] 62867/69 Headings C2A and C2C Novel acid-addition salts of amino-penicillins and arylsulphonic acids, having the general Formula 1 or an ester or amide thereof, wherein R is an amino-containing aliphatic or aromatic residue, R<SP>9</SP> is a substituted or unsubstituted aryl group, R<SP>10</SP> is an oxygen atom or a direct bond and R<SP>11</SP> is phenylene or alkylene, are prepared by treating an aqueous solution of a corresponding amino penicillin or a salt, ester or amide thereof, with a sulphonic acid of formula or a salt thereof, at pH 0À5 to 3À5 and isolating the resulting precipitate of the acid-addition salt. The amides or esters may then be hydrolysed to the sulphonate of the free penicillanic acid, e.g. enzymically or chemically. Aminopenicillins may be those wherein R is optionally substituted α-aminobenzyl, α-aminocycloalkyl, α - aminocycloalkenyl, or α - amino - 1- or 2- indanyl. The amino group may be primary, secondary or tertiary, and may be linked to the 6-nitrogen atom of the penicillin by a group -CR<SP>16</SP>R<SP>17</SP>-, wherein R<SP>16</SP> and R<SP>17</SP> separately are H, alkyl or phenyl or together with the carbon atom form a cycloalkyl ring, such compounds being adducts of ketones of formula R<SP>16</SP>.CO.R<SP>17</SP> with the ammo-penicillin. R<SP>9</SP> may be, e.g., phenyl, biphenyl, naphthyl, phenylcarbamylphenyl or phenylcarbamyl naphthyl. The sulphonic acid or its salt is preferably added as an aqueous solution, and the reaction mixture may contain a water-immiscible solvent, e.g. esters, ketones, or aromatic or aliphatic hydrocarbons which may be halogenated. The preparation of the acid-addition salts is useful as a means for purifying amino-penicillins formed, e.g., by acylation of 6-APA, from byproducts and starting materials, the acidaddition salt being precipitated from the crude reaction mixture and subsequently converted to the amino-penicillin, e.g. by hydrolysis with an amine or an inorganic base. Biphenylsulphonic acid monohydrate and diphenylethersulphonic acid monohydrate are prepared by reacting biphenyl, and diphenylether respectively, with chlorosulphonic acid. The following compounds are each reacted with propane-sultone in alcoholic NaOH: salicylanide, -naphthol #-naphthol, 2-hydroxydiphenyl, 4-hydroxydiphenyl, and 2- hydroxy-1-naphthoic anilide to give sodium 3- substituted propanesulphonates wherein the substituent group is: 2-carbanilidophenoxy, 1- naphthoxy, 2-naphthoxy, 2-phenylphenoxy, 4-phenylphenoxy, and 1-carbanilido-2-naphthoxy respectively. Pharmaceutical compositions having antibiotic activity against Gram-positive and Gramnegative bacteria comprise an amino-penicillin acid-addition salt of Formula 1 as previously defined herein in association with a pharmaceutically acceptable carrier.