Claims
- 1. A process for preparing a cis sulfinyl chloride of the formula ##STR35## which comprises the step of reacting a penicillin sulfoxide of the formula ##STR36## with an N-chloro halogenating agent at a temperature of from about 75.degree. C. to about 135.degree. C. in an inert solvent and under anhydrous conditions; in which, in the above formulae, R.sub.1 is a carboxylic acid protecting group; and R is (1) an imido group of the formula ##STR37## in which Rhd 2 is C.sub.2 -C.sub.4 alkenylene or 1,2-phenylene; (2) an amido group of the formula ##STR38## in which R.sub.3 is (a) hydrogen, C.sub.1 -C.sub.3 alkyl, halomethyl, cyanomethyl benzyloxy, 4-nitrobenzyloxy, t-butyloxy, 2,2,2-trichloroethoxy, 4-methoxybenzyloxy, 3-(2-chlorophenyl)-5-methylisoxazol-4-yl;
- (b) the group R' in which R' is phenyl or phenyl substituted with 1 or 2 halogens, protected hydroxy, nitro, cyano, trifluoromethyl, C.sub.1 -C.sub.4 alkyl, or C.sub.1 -C.sub.4 alkoxy;
- (c) a group of the formula R"-(Q).sub.m -CH.sub.2 - in which R" is R' as defined above, 1,4-cyclohexadienyl, 2-thienyl, or 3-thienyl; m is 0 or 1; and Q is O or S; subject to the limitation that when m is l, R" is R'; or
- (d) a group of the formula ##STR39## in which R" is as defined above, and W is protected hydroxy or protected amino;
- (3) an imidazolidinyl group of the formula ##STR40## in which R" is as defined above and U is nitroso or acetyl; or R is (4) an imido group of the formula ##STR41## in which R' is as defined above, m is 0 or 1, and R.sub.7 is C.sub.1 -C.sub.3 alkyl, C.sub.1 -C.sub.3 haloalkyl, C.sub.1 -C.sub.3 alkoxy, or 2,2,2-trichloroethoxy.
- 2. Process of claim 1, in which R is
- (1) an imido group of the formula ##STR42## in which R.sub.2 is C.sub.2 -C.sub.4 alkenylene or 1,2-phenylene; (2) an amido group of the formula ##STR43## in which R.sub.3 is (a) hydrogen, C.sub.1 -C.sub.3 alkyl, halomethyl, cyanomethyl, benzyloxy, 4-nitrobenzyloxy, t-butoxyloxy, 2,2,2-trichloroethoxy, 4-methoxybenzyloxy, 3-(2-chlorophenyl)-5-methylisoxazol-4-yl;
- (b) the group R' in which R' is phenyl or phenyl substituted with 1 or 2 halogens, protected hydroxy, nitro, cyano, trifluoromethyl, C.sub.1 -C.sub.4 alkyl, or C.sub.1 -C.sub.4 alkoxy; or
- (c) a group of the formula R"-(Q).sub.m -CH.sub.2 - in which R" is R' as defined above, 1,4-cyclohexadienyl, 2-thienyl, or 3-thienyl; m is 0 or 1; and Q is O or S; subject to the limitation tht when m is 1, R" is R';
- (3) an imidazolidinyl group of the formula ##STR44## in which R" is as defined above and U is nitroso or acetyl; or R is (4) an imido group of the formula ##STR45## in which R' is as defined above, m is 0 or 1, and R.sub.7 is C.sub.1 -C.sub.3 alkyl, C.sub.1 -C.sub.3 haloalkyl, C.sub.1 -C.sub.3 alkoxy, or 2,2,2-trichloroethyl.
- 3. Process of claim 2, in which R is a group of the formula ##STR46##
- 4. Process of claim 3, in which R" is R'.
- 5. Process of claim 4, in which R' is phenyl.
- 6. Process of claim 5, in which m is 0.
- 7. Process of claim 5, in which m is 1.
- 8. Process of claim 7, is which Q is oxygen.
- 9. Process of claim 3, in which R" is 2-thienyland m is zero.
- 10. Process of claim 1, in which R.sub.1 is C.sub.1 -C.sub.4 alkyl, 2,2,2-trihaloethyl, 2-iodoethyl, benzyl, p-nitrobenzyl, succinimidomethyl, phthalimidomethyl, p-methoxybenzyl, benzhydryl, C.sub.2 -C.sub.6 alkanoyloxymethyl, dimethylallyl, phenacyl, or p-halophenacyl.
- 11. Process of claim 10, in which R.sub.1 is methyl, benzyl, p-nitrobenzyl, p-methoxybenzyl, benzhydryl, or 2,2,2-trichloroethyl.
- 12. Process of claim 1, in which the reaction is carried out in the presence of a non-alkaline acid scavenger.
- 13. Process of claim 1, in which the non-alkaline acid scavenger is propylene oxide.
- 14. Process of claim 1, in which the reaction is carried out in the presence of toluene as solvent.
- 15. Process of claim 1, in which the N-chloro halogenating agent is a compound of the formula ##STR47## in which R.sub.4 is hydrogen, chloro, C.sub.1 -C.sub.3 alkyl, cyclohexyl, phenyl, or phenyl substituted with chloro, bromo, methyl, or nitro, and R.sub.5 is R.sub.6 -X- in which R.sub.6 is C.sub.1 -C.sub.3 alkyl, cyclohexyl, phenyl, or phenyl substituted with chloro, bromo, methyl, or nitro, and X is ##STR48## or --SO.sub.2 --; or R.sub.4 and R.sub.5 taken together with the nitrogen to which they are bonded define a heterocyclic structure of the formula ##STR49## in which Y is o-phenylene, or --(CH.sub.2).sub.n -- in which n is 2 or 3; or a structure of the formula ##STR50## in which Z is Y as hereinbefore defined or a group of the formula ##STR51## in which A is hydrogen or methyl.
- 16. Process of claim 15, in which the N-chloro halogenating agent has the formula ##STR52## in which Y is o-phenylene or --CH.sub.2 --C.sub.2 --.
- 17. Process of claim 16, in which the N-chloro halogenating agent is N-chlorosuccinimide.
- 18. Process of claim 16, in which the N-chloro halogenating agent is N-chlorophthalimide.
- 19. Process of claim 15, in which the N-chloro halogenating agent is ethyl dichlorourethane.
CROSS REFERENCE
This is a division, of application Ser. No. 673,017 filed Apr. 2, 1976, now U.S. Pat. 4,081,440 which is a continuation-in-part of application Ser. No. 632,732 filed Nov. 19, 1975, and now abandoned, which is a continuation-in-part of application Ser. No. 536,273 filed Dec. 24, 1974, and now abandoned.
Non-Patent Literature Citations (2)
Entry |
ishimaru et al., Bul. Chem. Soc., Japan 48, 2989-2990. |
Chou et al., J. Amer. Chem. Soc. 96, 1609-1610 (1974). |
Divisions (1)
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Number |
Date |
Country |
Parent |
673017 |
Apr 1976 |
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Continuation in Parts (2)
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Number |
Date |
Country |
Parent |
632732 |
Nov 1975 |
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Parent |
536273 |
Dec 1974 |
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