Tramadol hydrochloride (T), (±)-cis-2-[(dimethylamino)-
methyl]-1-(3-methoxyphenyl)cyclohexanol (1) [1-7] is a
centrally acting analgesic agent used in the treatment of
moderate to severe pain and as an alternative to opiates [8].
The sensitive analysis for drugs of abuse in seized materials
or biological fluids has become important for forensic and
toxicological laboratories. High performance liquid chromatography
(HPLC) with ultraviolet (UV) [9-13] is one of the
methods of choice for the analysis of drugs in biological
samples. Tramadol contains a weakly absorping chromophore
in its molecule [14]. Subsequently, UV detection is not suitable
for the determination of low tramadol concentrations. Therefore,
the development of a derivatization procedure that
improves both chromatographic detection (sensitivity) and
separation is an area of major interest in the analysis of
tramadol. Usually, highly conjugated aromatic compounds
such as acid chlorides are used in UV-visible derivatization
[15-18]. In view of the previous applications and in continuation
of our interest in synthesis of some fused and spiroheterocycles
[19-26], the aim of this work was to synthesize
new tramadol derivatives to improve their sensitivity for
detection with HPLC.