Synthesis of oxindoles from anilines and intermediates therein

Abstract

Preparing oxindoles and intermediates therefor by reacting an N-haloaniline with β-thio ester or β-thio amides to form an azasulfonium halide, reacting the azasulfonium halide with a base to form an ortho[thio-ether (hydrocarbonoxycarbonyl) alkyl]aniline, or a [thio-ether (aminocarbonyl) alkyl]aniline, reacting the ortho-substituted aniline with an acid to form a 3-thio-ether-2-oxindole, and then reducing the 3-thio-ether-2-oxindole with Raney Nickel to form the 2-oxindole.

I claim: 
     
       1. A process for preparing 2-oxindoles which comprises a. reacting an N-haloaniline with a β-thio compound selected from the group consisting of a lower-alkyl β-thioalkanoate ester and a lower-alkyl β-thioalkanoyl acylamide in organic liquid diluent under substantially anhydrous conditions at a temperature of from about -78° C to about 10° C to form an azasulfonium salt;   b. reacting the azasulfonium salt from step (a) with a substantially anhydrous base which will cause formation of an ylid intermediate to form an .[.ortho-[(thioalkyl) (alkylthiocarbonyl)methyl]-aniline,.]. .Iadd.ortho-[1-(thioalkyl) (lower-alkyloxycarbonyl)-methyl]-aniline, when the β-thio compound of step (a) is a lower-alkyl β-thioalkanoate ester, and an ortho [1-(thioalkyl) (lower-alkylaminocarbonyl) methyl]-aniline when the β-thio compound of step (a) is a lower-alkyl β-thioalkanoyl acylamide, .Iaddend.   c. heating the ortho-substituted aniline from step (b) to from about 50° C to about 150° C or acidifying the substituted aniline from step (b) to form a 3-thioalkyl-2-oxindole, and   d. desulfurizing the 3-thioalkyl-2-oxindole from step (c) to form the 2-oxindole.   
     
     
       2. A process as defined in claim 1 wherein an N-chlorobenzocaine is converted to a 5-carboethoxy-2-oxindole. 
     
     
       3. A process as defined in claim 1 wherein an N-chlorotoluidine is converted to a methyl-substituted-2-oxindole. 
     
     
       4. A process as defined in claim 1 wherein an N-chloronitroaniline is converted to a nitro-substituted-2-oxindole. 
     
     
       5. Process as defined in claim 1 wherein the desulfurization is .[.carrieid.]. .Iadd.carried .Iaddend.out with the employment of Raney nickel.