Process for manufacture of in vivo stain composition

Abstract

A process for synthesizing 2-amino-5-dimethlyaminophenyl thiosulfonic acid comprises the step of oxidizing N,N′-dimethyl-ρ-phenylene-diamine in the presence of a source of thiosulfate ions, while maintaining the temperature of the reaction mixture not higher than about 10° C. This compound is useful as an intermediate in the synthesis of toluidine blue ∘. A process for manufacturing toluidine blue ∘ with improved yield, includes the step of preparing the intermediate 2-amino-5-diethylaminopropyl thiosulfonic acid according to the above described procedure.

1 . In a process for manufacturing toluidine blue ∘ (“TBO”), which process includes the steps of 
 oxidizing N,N″-dimethly-ρ-phenylene diamine in a first reaction mixture,  
 introducing a source of thiosulfate ions into said first reaction mixture, to form a first intermediate, 2-amino-5-dimethylaminophenyl thiosulfonic acid,  
 further oxidizing and condensing said first intermediate with o-toluidine, to form a second intermediate, indamine-thiosulfonic acid,  
 further oxidizing said second intermediate to close the indamine ring thereof, to form a TBO-containing reaction product in a third reaction mixture, and  
 separating the TBO-containing reaction product from the third reaction mixture,  
 the improvement for improving the overall yield of TBO from said process, comprising the steps of introducing said source of thiosulfate ions into said first reaction mixture, while maintaining the temperature of said first reaction mixture at a temperature not higher than about 100° C.  
 
     
     
         2 . A process for synthesizing 2-amino-5-dimethlyaminophenyl thiosulfonic acid, comprising the step of oxidizing N,N″-dimethyl-ρ-phenylene-diamine in the presence of a source of thiosulfate ions, while maintaining the temperature of the reaction mixture not higher than about 10° C.