Synthesis and Characterization of a Butenafine Analogue

Aims: The study aims: (I) To synthesise N-(4-(tert-butyl) benzyl)-1-(4-tert-butyl) phenyl)-N-methyl
methanaminium chloride, an analogue of butenafine from tertiary-butyl benzyl derivatives, (II) to
compare the solvent actions of Tetrahydrofuran (THF), acetonitrile, methanol and 1,2-dichloroethane
(DCE), and the reducing efficiencies of NaBH4 and sodium triacetoxyborohydride (STAB) during the
synthesis.
Study Design: The study involved laboratory experiments leading to the synthesis of the target
compound by varying the non-aqueous solvents used, the reducing agent and the temperature of the
operations. Silica chloride catalyst was used to speed up the reaction in one of the syntheses and in
each synthesis, Thin Layer Chromatography was used to monitor the progress of the reaction. The
time taken by each reaction and the yield were used as the basis for determining the solvent action
and the reducing efficiency.
Place and Duration of Study: M.Sc. Access controlled Teaching Laboratory, School of Chemistry,
Newcastle University, New castle upon Tyne, United Kingdom from June to August 2012.
Methodology: Reductive amination was carried out by reacting 4-tert-butylbenzaldehyde and 4-tertbutylbenzylamine,
using the direct and then the indirect approaches. This was followed by methylation
using the Eschweiler-Clarke reaction in each of the two approaches. The time taken by each reaction
was monitored and the product of each approach was characterised by EIS-MS, 1H NMR, 13C NMR
and FTIR.
Results: 1,2-dichloroethane gave the best solvent action at 40°C (Yield: 75%) and NaBH4 gave the
best-reducing action with silica chloride catalyst at 25°C (Yield: 50%). At the end of each synthesis, in
all obtained products, 1H NMR spectrum gave a single peak of 18 hydrogen atoms at 1.3 -1.5 ppm for
the existence of 6 methyl groups in the two tertiary-butyl substituents, the 13C NMR spectrum also
showed a peak at 31-32 ppm for the six methyl carbon atoms in the two tertiary-butyl substituents,
the FTIR spectrum showed a strong band at 2460 cm-1 for the presence of a tertiary ammonium ion
and finally the EIS-MS gave a mass to charge ratio of 324.2693 as a confirmation of the relative
molecular mass of the compound.
Conclusion: The target compound can be synthesised by both direct and the indirect approaches of
reductive amination in any of the solvents tested with/without a catalyst at room or elevated
temperature using NaBH4 or STAB as a reducing agent but the best solvent action can be achieved
with DCE at 40°C and the best-reducing action can be achieved with NaBH4 in the presence of silica
chloride.