Issue in Honor of Prof. Eusebio Juaristi ARKIVOC 2005 (vi) 287-292
In summary, we have demonstrated an efficient and general synthesis of tertiary amines by direct N-alkylation of secondary amines with alkyl halides in the presence of Huenig’s base. The reaction is applicable to aliphatic halides and aliphatic amines and is suitable for use in the presence of other functional groups without the need for protecting them. Short reaction times, high product yields, scalability, absence of quaternary ammonium salt formation and operationally convenient conditions are some of the advantages that render this method favorable over other previously reported methods.
Experimental Section
General Procedures. Secondary amine (0.500 g, 1 mol eq.), N,N-diisopropylethylamine (1.5 mol eq.), alkyl halide (1.1 mol eq.) and 10 mL acetonitrile were placed in a round bottom flask and stirred at room temperature under nitrogen. After completion of the reaction (monitored by TLC) the reaction mixture was evaporated to dryness under reduced pressure. The residue was dissolved in 5 mL of CH2Cl2 and washed with 5 mL of distilled water. The aqueous layer was washed with 3 x 5 mL fractions of CH2Cl2. The collected organic fractions were dried over MgSO4 and the solvent was removed under reduced pressure to yield the crude product.
Compound characterization. 1H NMR spectra acquired on a Varian 300 NMR spectrometer (300 MHz) at 295K in CDCl3 containing TMS as internal standard. 1H NMR spectra for the reported compounds were consistent with literature data.3a,3d,11a-e
Acknowledgements
This work was supported by the start-up fund provided by the University of Oklahoma, Department of Chemistry and Biochemistry. J.L.M. thanks the University of Oklahoma, Department of Chemistry and Biochemistry, the University of Oklahoma Alumni Fellowship, and the U.S. Department of Education GAANN Fellowship for financial support. S.M.T. thanks the University of Oklahoma, Honors College and UROP program for financial support.
References
1. Seayad, A.; Ahmed, M.; Klein, H.; Jackstell, R.; Gross, T.; Beller, M. Science 2002, 297, 1676. 2. (a) Bradshaw, J. S.; Krakowiak, K. E.; Izatt, R. M. Tetrahedron 1992, 48, 4475. (b) Blagbrough, I. S.; Carrington, S.; Geall, A. J. Pharm. Sci. 1997, 3, 223. (c) Bergeron, R. J.; Feng, Y.; Weimer, W. R.; McManis, J. S.; Dimova, H.; Porter, C.; Raisler, B.; Phanstiel, O. J. Med. Chem. 1997, 40, 1475. ISSN 1424-6376 Page 291 ©ARKAT USA, Inc
