Synthesis and characterization of novel azo-morphine derivatives for possible use in abused drugs analysis

A new simple and fast spectroscopic method was presented as a new marker for heroin use. Novel azo-morphine derivatives with spectroscopic absorption peaks ranging from 330–470 nm, were synthesized by the coupling of morphine (M) and 6-acetyl morphine (6-AM) with freshly prepared diazonium salt of aniline hydrochloride at 0 °C. However, no reaction was observed with codeine under the same reaction conditions. Separation of azo dyes was performed by TLC using tetrahydrofuran and dichloromethane in the ratio 1:1. The chemical structure of the products was established by their microanalysis, NMR, IR, UV–vis, and mass spectroscopies. Electronic absorption and excitation spectra of the dyes were measured in solvents of different polarities. The dyes exhibited positive solvatochromism, i.e., a bathochromic band shift as the solvent polarity is increased. Also, the fluorescence quantum yield was sensitive to the polarity and the pH of the medium. The UV–vis spectroscopy of spiked compounds in human urine samples was also reported. The drugs (M, 6-AM and mixture of both) were coupled with freshly prepared diazonium salt even at very low concentration of the drugs 10−9 M.

Graphical abstractAzo compounds were synthesized by first reacting aniline hydrochloride with nitrous acid (HNO2) to produce an aryldiazonium ion. This ion can couple with a nucleophilic morphine (M) or 6-acetyl morphine (6-AM) in basic solution to produce the azo-M (phenyl-2-azo-morphine 1, 76% and phenyl-2-azo-morphine sodium salt 2, 24%) and azo-6-AM (phenyl-2-azo-6-acetyl morphine 3, 77% and phenyl-2-azo-6-acetyl morphine sodium salt 4, 23%) in reasonable yields. The resulting azo compounds were highly fluorescent in most of the organic solvents and water.Figure optionsDownload full-size imageDownload as PowerPoint slide