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A novel method for N-alkylation of aliphatic amines with ethers over γ-Al2O3

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Abstract

A novel and simple method for the N-alkylation of amines with different ethers as alkylating reagents has been developed, using cheap γ-Al2O3 as the catalyst at atmospheric pressure in the temperature range of 260–320°C. For example, the reaction of equimolar amounts of morpholine and diethyl ether gave N-ethylmorpholine quantitatively. The present catalytic system is applicable to the N-alkylation of both primary and secondary amines. Since only water is generated as byproduct, the protocol proved to be eco-friendly and atom-economic.

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References

  • Adima, A., Bied, C., Moreau, J. J. E., & Man, M. W. C. (2004) Facile cleavage of Si.C bonds during the sol-gel hydrolysis of aminomethyltrialkoxysilanes - a new method for the methylation of primary amines. European Journal of Organic Chemistry, 2004, 2582–2588. DOI: 10.1002/ejoc.200400079.

    Article  CAS  Google Scholar 

  • Baiker, A., & Kijenski, J. (1985) Catalytic synthesis of higher aliphatic amines from the corresponding alcohols. Catalysis Reviews: Science and Engineering, 27, 653–697. DOI: 10.1080/01614948508064235.

    Article  CAS  Google Scholar 

  • Baiker, A., & Richarz, W. (1977) Synthesis of long chain aliphatic amines from the corresponding alcohols. Tetrahedron Letters, 18, 1937–1938. DOI: 10.1016/S0040-4039(01)83646-7.

    Article  Google Scholar 

  • Brown, A. B., & Reid, E. E. (1924) Catalytic alkylation of aniline. Journal of the American Chemical Society, 46, 1836–1839. DOI: 10.1021/ja01673a011

    Article  CAS  Google Scholar 

  • Chiappe, C., & Pieraccini, D. (2003) Direct mono-N-alkylation of amines in ionic liquids. chemoselectivity and reactivity. Green Chemistry, 5, 193–197. DOI: 10.1039/b211340f.

    Article  CAS  Google Scholar 

  • Dobereiner, G. E., & Crabtree, R. H. (2010) Dehydrogenation as a substrate-activating strategy in homogeneous transition-metal catalysis. Chemical Reviews, 110, 682–703. DOI: 10.1021/cr900202j.

    Article  CAS  Google Scholar 

  • Gawande, M. B., Deshpande, S. S., Satam, J. R., & Jayaram, R. V. (2007) A novel N-alkylation of amines by alkyl halides on mixed oxides at room temperature. Catalysis Communications, 8, 576–582. DOI: 10.1016/j.catcom.2006.08.011.

    Article  CAS  Google Scholar 

  • Guillena, G., Ramon, D. J., & Yus, M. (2010) Hydrogen autotransfer in the N-alkylation of amines and related compounds using alcohols and amines as electrophiles. Chemical Reviews, 110, 1611–1641. DOI: 10.1021/cr9002159.

    Article  CAS  Google Scholar 

  • Guillena, G., Ramon, D. J., & Yus, M. (2007) Alcohols as electrophiles in C-C bond-forming reaction: The hydrogen autotransfer process. Angewandte Chemie International Edition, 46, 2358–2364. DOI: 10.1002/anie.200603794.

    Article  CAS  Google Scholar 

  • Hamid, M. H. S. A., Slatford, P. A., & Williams, J. M. J. (2007) Borrowing hydrogen in the activation of alcohols. Advanced Synthesis & Catalysis, 349, 1555–1575. DOI: 10.1002/adsc.200600638.

    Article  CAS  Google Scholar 

  • Hamid, M. H. S. A., & Williams, J. M. (2007) Ruthenium catalyzed N-alkylation of amines with alcohols. Chemical Communications, 7, 725–727. DOI: 10.1039/b616859k.

    Article  CAS  Google Scholar 

  • Hargis, D. C. (1990). U.S. Patent No. 4,929,764. Washington, D.C.: U.S. Patent and Trademark Office.

    Google Scholar 

  • Heydari, A., Khaksar, S., Esfandyari, M., & Tajbakhsh, M. (2007) A novel one-pot reductive amination of aldehydes and ketones with lithium perchlorate and zirconium borohydride-piperazine complexes. Tetrahedron, 63, 3363–3366. DOI: 10.1016/j.tet.2007.02.026.

    Article  CAS  Google Scholar 

  • Kawaguchi, M., Ohashi, J., Kawakami, Y., Yamamoto, Y., & Oda, J. C. (1985) Facile synthesis of morpholines and azacrown ethers by ozonolysis of cylic olefins and reductive N-alkylation. Synthesis, 1985, 701–703.

    Article  Google Scholar 

  • Ko, A.-N., Yang, C.-L., Zhu, W.-D., & Lin, H.-E. (1996) Selective N-alkylation of aniline with methanol over γ-alumina. Applied Catalysis A: General, 134, 53–66. DOI: 10.1016/0926-860X(95)00209-X.

    Article  CAS  Google Scholar 

  • Lai, J. T. (1980) Hindered amines. Synthesis of hindered acylic α-aminoacetamides. Journal of Organic Chemistry, 45, 3671–3673. DOI: 10.1021/jo01306a025.

    Article  CAS  Google Scholar 

  • Li, K.-T., & Peng, Y.-C. (1994) Methylation of n-butylamine over solid-acid catalysts. Applied Catalysis A: General, 109, 225–233. DOI: 10.1016/0926-860X(94)80120-7.

    Article  CAS  Google Scholar 

  • Marsella, J. A. (1987) Homogeneously catalyzed synthesis of β-amino alcohols and vicinal diamines from ethylene glycol and 1,2-propanediol. Journal of Organic Chemistry, 52, 467–468. DOI: 10.1021/jo00379a035.

    Article  Google Scholar 

  • Martínez, R., Ramon, D. J., & Yus, M. (2009) Selective N-monoalkylation of aromatic amines with benzylic alcohols by a hydrogen autotransfer process catalyzed by unmodified magnetite. Organic & Biomolecular Chemistry, 7, 2176–2181. DOI: 10.1039/b901929d.

    Article  CAS  Google Scholar 

  • Nacario, R., Kotakonda, S., Fouchard, D. M. D., Tillekeratne, L. M. V., & Hudson, R. A. (2005) Reductive monoalkylation of aromatic and aliphatic nitro compounds and the corresponding amines with nitriles. Organic Letters, 7, 471–474. DOI: 10.1021/ol047580f.

    Article  CAS  Google Scholar 

  • Narayanan, S., & Deshpande, K. (2000) Aniline alkylation over solid acid catalysts. Applied Catalysis A: General, 199, 1–31. DOI: 10.1016/S0926-860X (99)00540-2.

    Article  CAS  Google Scholar 

  • Nixon, T. D., Whittlesey, M. K., & Williams, J. M. J. (2009) Transition metal catalysed reactions of alcohols using borrowing hydrogen methodology. Dalton Transactions, 39, 753–762. DOI: 10.1039/b813383b.

    Article  CAS  Google Scholar 

  • Ouk, S., Thiebaud, S., & Borredon, E. (2005) N-Methylation of nitrogen-containing heterocycles with dimethyl carbonate. Synthetic Comunications, 35, 3021–3026. DOI: 10.1080/00397910500278578.

    Article  CAS  Google Scholar 

  • Romera, J. L., Cid, J. M., & Trabanco, A. A. (2004) Potassium iodide catalysed monoalkylation of anilines under microwave irradiation. Tetrahedron Letters, 45, 8797–8800. DOI: 10.1016/j.tetlet.2004.10.002

    Article  CAS  Google Scholar 

  • Salvatore, R. N., Yoon, C. H., & Jung, K. W. (2001) Synthesis of secondary amines. Tetrahedron, 57, 7785–7811. DOI: 10.1016/S0040-4020(01)00722-0.

    Article  CAS  Google Scholar 

  • Suzuki, K., Okano, K., Nakai, K., Terao, Y., & Sekiya, M. (1983) Reductive rearrangement of 2-chloroalkanamides with lithium aluminum hydride leading to α-methyl-branched aliphatic amines. Synthesis, 1983, 723–725.

    Article  Google Scholar 

  • Takasaki, M., Motoyama, Y., Higashi, K., Yoon, S.-H., Mochida, I., & Nagashima, H. (2007) Ruthenium nanoparticles on nano-level-controlled carbon supports as highly effective catalysts for arene hydrogenation. Chemistry - An Asian Journal, 2, 1524–1533. DOI: 10.1002/asia.200700175.

    Article  CAS  Google Scholar 

  • Valot, F., Fache, F., Jacquot, R., Spagnol, M., & Lemaire, M. (1999) Gas-phase selective N-alkylation of amines with alcohols over γ-alumina. Tetrahedron Letters, 40, 3689–3692. DOI: 10.1016/S0040-4039(99)00588-2.

    Article  CAS  Google Scholar 

  • Watanabe, Y., Tsuji, Y., & Ohusugi, Y. (1981) The ruthenium catalyzed N-alkylation and N-heterocyclization of aniline using alcohols and aldehydes. Tetrahedron Letters, 22, 2667–2670. DOI: 10.1016/S0040-4039(01)92965-X.

    Article  CAS  Google Scholar 

  • Winans, C. F., & Adkins, H. (1932) The alkylation of amines as catalyzed by nickel. Journal of the American Chemical Society, 54, 306–312. DOI: 10.1021/ja01340a046.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Chemical and Biochemical Engineering, Zhejiang University, Hangzhou, 310027, China

    Hangeng Chen, Tao Zhang, Chao Qian & Xinzhi Chen

  2. SINOPEC Jinling Company, Nanjing, 210033, China

    Hangeng Chen

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  1. Hangeng Chen
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  2. Tao Zhang
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  3. Chao Qian
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  4. Xinzhi Chen
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Correspondence to Chao Qian.

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Chen, H., Zhang, T., Qian, C. et al. A novel method for N-alkylation of aliphatic amines with ethers over γ-Al2O3 . Chem. Pap. 64, 537–540 (2010). https://doi.org/10.2478/s11696-010-0033-7

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  • DOI: https://doi.org/10.2478/s11696-010-0033-7

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