Detection and identification of side reactions of halogenated hydrocarbon solvents with amines of pharmaceutical interest by secondary processes to the neutralizations of sulphonphthaleinic dyes with these amines

Article abstract of DOI:10.1002/jps.2600830223

The neutralization reactions between amines and diprotic acid dyes in organic solvents generate {dye^-, amineH⁺} and {dye^2-, (amineH⁺)₂} ion associates that show two absorption bands in the visible spectrum. An unidentified third absorption band; which appears with a high amine concentration, proves that halogenated hydrocarbon solvents (dichloromethane, chloroform, 1,2-dichloroethane, and carbon tetrachloride) give side reactions with amines (atropine, tropine, quinine, ephedrine, and ajmaline) that generate a quaternary ammonium salt, N-halogenalkylammonium halide ({N⁺- RX,X^-}). The molecular weight of the quaternary ammonium salt is the sum of the amine and that of the solvent. The {N⁺-RX,X^-} ion associated reacts with {dye^2-, (amineH⁺)₂} by substitution reactions, forming {dye^2-, amineH⁺, N⁺-RX} and {dye^2-, (N⁺-RX)₂} ion associates that justify the third absorption band. The amine-solvent side reactions are of first order with respect to the amine, being very slow processes with rate constant values from 399.4 h^-1 (tropine-dichloromethane reaction) to 15.8 h^-1 (atropine-1,2-dichloroethane reaction). Rate constants increase with the basicity of the amine measured in the halogenated hydrocarbons employed. Rate constants also increase with a reduction in the number of the halogen atoms present in the halogenated solvent. The new visible absorption band that appears in the amine-dye neutralization gives a quick colorimetric test to bring to light this kind of side reaction in these solvents.