Synthesis of stable isotope labelled cathinone derivatives as internal standards for forensic and pharmaceutical analysis.

Abstract

The synthetic work presented in this thesis has focused on identifying efficient routes towards stable isotope labelled cathinone derivatives. These compounds will act as internal standards for forensic and pharmaceutical analysis. A series of eighteen pure synthetic cathinone derivatives 1-13 have been synthe- sized by using known methods, or extrapolation of known methods. Seventeen of these, including five deuterated compounds (3b, 4b, 11b, 12b and 13), have been prepared following the general two- or three-step process depicted in Scheme 1. The desired amine products have been conveniently isolated as their corresponding hydrochloride salts to high purity (97-99.9% UHPLC). The process rely on common starting materials and use certain common intermediates and similar reaction steps, thus allowing for a wide series of pure cathinone derivatives to be prepared rapidly and economically. Furthermore, a three-step process for the preparation of [13C6]-4-methylmethcathinone (3c) from [13C6]-toluene (24b) has been developed (see Scheme 2). The reported procedure involves an initial AlCl3-mediated Friedel Crafts acylation of 24b with propionic anhydride.