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Synthesis and Characterization of a Butenafine Analogue | Chapter 07 | Theory and Applications of Chemistry Vol. 3

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-tert-butylbenzylamine, 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.

Author(s) Details

M. A. Muhammad
Department of Chemistry, Ibrahim Badamasi Babangida University, P.M.B 11, Lapai, Niger State, Nigeria.

A. M. Jimoh
Department of Chemistry, Ibrahim Badamasi Babangida University, P.M.B 11, Lapai, Niger State, Nigeria.

A. Awwal
Department of Chemistry, Ibrahim Badamasi Babangida University, P.M.B 11, Lapai, Niger State, Nigeria.

View Volume: http://bp.bookpi.org/index.php/bpi/catalog/book/104

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