Process for preparing azetidinone derivatives

Details Process for preparing azetidinone derivatives Process for preparing azetidinone derivatives

1984-05-01

1986-11-11

Berch, Mark L.

Organic compounds -- part of the class 532-570 series

Organic compounds

Unsubstituted hydrocarbyl chain between the ring and the -c-...

546187, 546193, 546194, 546198, 546199, 546209, 546210, 546208, 546256, 546270, 546275, 546276, 546277, 540355, C07D20508, C07D40312, C07D40112, C07D40114

Patent

active

046221786

DESCRIPTION:

BRIEF SUMMARY
TECHNICAL FIELD

This invention relates to a process for preparing azetidinone derivatives and more particularly to a process for preparing azetidinone derivatives represented by the formula ##STR2## wherein R.sup.1 represents a straight-chain or branched-chain lower alkyl group, substituted or unsubstituted aryl group, substituted or unsubstituted phenylmethyl group or substituted or unsubstituted phenyloxymethyl group, R.sup.2 represents hydrogen atom, an optionally substituted hydrocarbon residue or protective group for amino group selected from the class consisting of acyl, silyl, sulfonyl and phosphonyl derived from organic or inorganic acid, and R.sup.3 represents a substituted or unsubstituted aryl group or the residue of substituted or unsubstituted heterocyclic ring.
The azetidinone derivatives of the formula (I) are important compounds as intermediates for synthesizing cephalosporin-type antibiotics.
Conventional processes for preparing the azetidinone derivatives of the formula (I) include those which involve the reaction between thiol and sulfenic acid formed by thermal decomposition of penicillin sulfoxide, for example, the reaction of penicillin G-S-oxide with 2-mercaptobenzothiazole [T. Kamizya et al., Tetrahedron Lett., 3001 (1973)]. With this process, however, the amino-protecting group R.sup.2 of the compound (I) is restricted by the substituents of the penicillin which is one of the reactants. Processes are known for synthesizing the compounds (I) having various amino-protecting groups R.sup.2 for amino which processes comprise reacting a thiazolinoazetidinone derivative having the corresponding amino-protecting groups R.sup.2 with a sulphenyl halide in a hydrous organic solvent [S. Torii et al., Tetrahedron Lett., 2495 (1982)]. However, this process involves the preparation of a sulfenyl halide by reacting the corresponding disulfide or thiol with a halogen such as chlorine or bromine and thus entails complicated reaction operation. Further the process requires an excess amount of a sulfenyl halide because of its decomposition in a hydrous solution and involves a cumbersome treatment for separating the decomposed sulfenyl halide. For these reasons, the process poses problems in terms of commercial mass production.
We have conducted extensive research to develop a process using disulfide serving as an agent for converting the starting material to sulfenyl without employing halogen and found that the contemplated compound can be prepared by a simple procedure of reacting a compound having the skeleton of 7-oxo-4-thia-2,6-diazabicyclo[3,2,0]hepto-2-ene with an acid in a hydrous organic solvent in the presence of dibenzothiazolyldisulfide. The invention has been accomplished based on this novel finding.


DISCLOSURE OF THE INVENTION

This invention provides a process for preparing an azetidinone derivative represented by the formula ##STR3## wherein R.sup.1 represents a straight-chain or branched-chain lower alkyl group, substituted or unsubstituted aryl group, substituted or unsubstituted phenylmethyl group or substituted or unsubstituted phenyloxymethyl group, R.sup.2 represents hydrogen atom, an optionally substituted hydrocarbon residue or amino-protecting group selected from the class consisting of acyl, silyl, sulfonyl and phosphonyl derived from inorganic or organic acid, and R.sup.3 represents a substituted or unsubstituted aryl group or the residue of substituted or unsubstituted heterocyclic ring, the process comprising reacting a thiazolinoazetidinone derivative represented by the formula ##STR4## wherein R.sup.1 and R.sup.2 are as defined above with a sulphur-containing compound represented by the formula ##STR5## (in which R.sup.3 is as defined above and R.sup.4 and R.sup.5 each represent a cyclic or acyclic amine residue or imido residue) in the presence of an acid in a hydrous organic solvent.
The process of this invention eliminates the need to use a sulfenyl halide which requires special care in handling and gives the contemplated compound in a high yield by carrying out a

REFERENCES:
Bennett, "Concise Chemical & Technical Dictionary", 3rd Edition 1974, p. 559.
Micetich et al, Can J. Chem 59, 1020 (1981).

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