title: 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.
abstract: The neutralization reactions between amines and diprotic acid dyes in organic solvents generate (dye-, amineH+) and [dye2-, (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 [dye2-, (amineH+)2] by substitution reactions, forming (dye2-, amineH+, N(+)-RX) and (dye2-, (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.
authors.affiliation: Departamento de Química-Física, Facultad de Farmacia, Universidad de Granada, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Hernandez Gainza
authors.forename: R I
authors.initials: RI
authors.lastname: Konyeaso
authors.forename: R A
authors.initials: RA
authors.lastname: Asenjo
mesh_terms: D000588:Amines / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D004396:Coloring Agents; D006846:Hydrocarbons, Halogenated / Q000737:chemistry*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008970:Molecular Weight; D012997:Solvents; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000588:Amines; D004396:Coloring Agents; D006846:Hydrocarbons, Halogenated; D012997:Solvents