Patent GB-1269997-A (GB)
Title: Alkenylmercapto compounds and process for their manufacture
Inventor: HEUSLER K
IPC: C07D499/00
Filed: 1969-07-16
Abstract: 1,269,997. Azetidinones, azetidino[3,2-d] thiazolidinones and pencillins. CIBA-GEIGY A.G. 16 July, 1969 [23 July, 1968; 11 Dec., 1968 (2)], No. 35886/69. Headings C2A and C2C. Novel compounds I (including optical isomers thereof) wherein Ac signifies acyl and R 2  is H or CHO, are obtained by thermally decomposing compounds II (obtained by opening the 5-membered ring of suitable penicillins utilizing, e.g. lead tetra-acetate; R 1  is an organic radical; II heated with tris-triphenyl-phosphino-rhodium chloride affords a rhodium complex as well as I) and, if desired, in a resulting compound I a formyl group R 2  is eliminated, and/or in a compound I with an acyl radical containing protected functional groups these groups are liberated, and/or a mixture of isomers is resolved. Hydrogenation of I affords the corresponding isopropyl-mercapto compounds. 4,4- Dimethyl - azetidino[3,2 - d]thiazolidin - 2 - one (obtained from I in which R 2  is H and Ac is tert.-butyloxy-carbonyl utilizing trifluoroacetic acid) is converted into compound III by interaction with phosgene; the corresponding tert.-butyl ester is obtained by treating III with tert.-butanol-in general, this process can be applied to compounds I wherein Ac is an acyl residue capable of being removed under acidic conditions utilizing a strong oxygen-containing acid and, if desired, in a resulting bicyclic compound an unsubstituted N-atom is acylated, optionally stepwise, e.g. as described in connection with III. 2 - α - (2 - Hydroxymethyl - 2 - propylmercapto)- 3 - α - (N - phenoxyacetylamino) - azetidin - 4 - one is obtained by treating 2-hydroxy-3,3-dimethyl- 6 - (N - phenoxyacetylamino)- 4 - thia - 1 - azabicyclo [3.2.0] heptan-7-one hydrate with sodium borohydride. The following penicillin reaction sequences are described: penicillin-V treated with sodium azide affords the corresponding acid azide which is heated to yield the corresponding isocyanate-the isocyanate group is reacted with 2,2,2 - trichloroethanol to afford the corresponding 2 - NH - CO 2 CH 2 CCl 3  compound which is converted into the corresponding 2-OH- compound (the hydrate thereof is also described) utilizing zinc in the presence of dimethylformamide and aqueous acetic acid (the 2-NHCO 2  CH 2 CHCl 2  compound is also described); similarly the sequence: penicillin-G, penicillin-G azide (via the triethylammonium salt of penicillin- G), penicillin-G isocyanate and the corresponding 2 - NH.CO 2 CH 2 CCl 3  (can be obtained directly from the azide) and 2-OH compounds; also the sequence: 6-amino-penicillanic acid, 6-NHCO 2 . tert. - butyl - penicillanic acid (utilizing tert.- butyl fluoroformate in the presence of triethylamine and hexamethyldisilazane) and the triethylammonium salt thereof, 6-NHCO 2 .tert-butylpenicillanic acid azide, isocyanate and 2-NHCO 2  CH 2 CCl 3  (a dicarbamate) and 2-OH compounds. Pharmaceutical preparations showing, in particular, activity against gram-positive bacteria, e.g. Staphylococcus aureus, contain as active ingredient compounds I; administration is, e.g. as tablets, dragees, capsules, suppositories, solutions, suspensions or emulsions.