Synthesis and characterization of methylsalicylate and acetaminophen silyl ether canditates for prodrugs

Abstract

Some silyl ethers of acetaminophen and methylsalicylate of general formula ArOSiRR′R″ ArOH = parahydroxyacetanilide or 2-hydroxybenzoic acid methyl ester; SiRR′R″ = trimethylsilyl, triethylsilyl, dimethyltert(Bu)silyl, triphenylsilyl, dimethylsilyl, tris(trimethylsilyl)silyl (sisyl) or dimethylvinylsilyl have been prepared and fully characterized. The compounds were prepared from the combination of either acetaminophen or methylsalicylate with the silyl chloride of these groups. Two methods were employed. In the first Et₃N was used in THF to remove HCl in coupling the silyl group to the organic substrate. In the other method imidazole as a base in dimethylformamide (DMF) were used. The effect of the silyl groups in providing stability to the compounds preventing or enhancing hydrolysis of the silicon-containing group was determined. The compounds were characterized by: NMR, IR, mass spectroscopy and elemental analysis (CHN) methods.