Jeffrey E. Rowe

Investigation of the impurities found in methamphetamine synthesised from pseudoephedrine by reduction with hydriodic acid and red phosphorus

The synthesis of methamphetamine from pseudoephedrine via the reduction with hydriodic acid and red phosphorus was studied and the impurities which were generated, along with the methamphetamine, were investigated. Some of the impurities found have been reported previously, while the diastereoisomers of N-methyl-N-(alpha- methylphenethyl)amino-1-phenyl-2-propanone and the cis-cinnamoyl derivative of methamphetamine are reported here for the first time. Further work on the sequence of reactions occurring in this reduction is also reported.

Differentiation of side chain isomers of methamphetamine using gas chromatography, high performance liquid chromatography and mass spectrometry

Abstract Eleven side chain positional isomers of methamphetamine can be distinguished from methamphetamine using a combination of the Marquis colour test, gas chromatography (GC), high performance liquid chromatography (HPLC) and mass spectrometry (MS). Many of the compounds gave identical colour tests, and several had similar mass spectral fragmentation patterns, but the combined technique of GC MS unequivocally differentiates all the isomers.

The preparation of methyl (E)- and (Z)-O-methylbenzothiohydroximates

A series of methyl (Z)-O-methylbenzothiohydroximates were prepared either by reaction of the corresponding (Z)-N-methoxybenzenecarboximidoyl bromides with potassium fluoride in dimethyl sulfoxide, or by reaction of N-methoxybenzamides with Lawesson’s reagent followed by alkylation. Irradiation of the Z isomers led to a photostationary equilibrium containing mixtures of approx. 40% E and 60% Z, from which the E isomers were isolated.

Nucleophilic attack on the carbon-nitrogen double bond leading to tetrahedral intermediates with conformationally restricted stereochemistry.

Methoxide ion substitution on 4-chloro-1H-2,3-benzoxazine 4 has been investigated. The rates of cyclization have been measured for (Z)- and (E)-O-(2-hydroxyethyl)benzohydroximoyl halides (PhC(X)=NOCH2CH2OH; X = Cl or Br) using potassium t-butoxide to generate alkoxide ions from the alcohols. The element effect for the Z and E isomers are kZBr/kZCl = 3.08 and kEBr/kECl = 2.38. The Z-to-E rate ratios are 0.25 (chlorides) and 0.33 (bromides). These reactions are proceeding by rate-determining nucleophilic attack by the alkoxide ion on the carbon–nitrogen double bond (AN# + DN). The restricted stereochemistry of the tetrahedral intermediates suggests that the E-hydroximoyl bromide and chloride may be undergoing unassisted ionization to form a zwitterionic intermediate that leads to product. Alternatively, the chair conformation of the tetrahedral intermediate may be undergoing a ring flip to a boat conformation in which there are antiperiplanar electron pairs that assist in the ionization of the bromide or chloride ion.