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Practical demethylation of aryl methyl ethers using an odorless thiol reagent

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Abstract

A highly practical method for demethylation of aryl methyl ethers employing a long-chain thiol has been developed. Under the conditions described herein, clean and fast conversions to the desired phenolic compounds have been achieved with a broad range of substrates. Unlike other thiolate-mediated methods, this newly developed protocol features in-situ generation of sodium alkylthiolate using NaOH, and is almost free from foul smells and potentially harmful gases. It therefore provides an attractive option for the demethylation of aryl methyl ethers.

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References

  • Dodge, J. A., Stocksdale, M. G., Fahey, K. J., and Jones, C. D., Regioselectivity in the alkaline thiolate deprotection of aryl methyl ethers. J. Org. Chem., 60, 739–741 (1995).

    Article  CAS  Google Scholar 

  • Fernandes, P. B., Mailman, R. B., and Nichols, D. E., Preparation of hexahydrobenzo-phenanthridines as dopamine receptor agonists for treatment of pulmonary edema. PCT Int. Appl., WO 2006012640 (2006).

  • Frey, L. F., Marcantonio, K. M., Chen, C. Y., Wallace, D. J., Murry, J. A., Tan, L., Chen, W., Dolling, U. H., and Grabowski, E. J. J., Practical synthesis of a highly functionalized thiazole ketone. Tetrahedron, 59, 6363–6373 (2003).

    Article  CAS  Google Scholar 

  • Ko, H. M., Lee, D. G., Kim, M. A., Kim, H. J., Park, J., Lah, M. S., and Lee, E., Total synthesis of (-)-blepharocalyxin D. Org. Lett., 9, 141–144 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Magano, J., Chen, M. H., and Clark, J. D., Nussbaumer, T., 2-(Diethylamino)ethanethiol, a new reagent for the odorless deprotection of aromatic methyl ethers. J. Org. Chem., 71, 7103–7105 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Nakatani, M., Nakamura, M., Suzuki, A., Inoue, M., and Katoh, T., A new strategy toward the total synthesis of stachyflin, a potent anti-influenza a virus agent: Concise route to the tetracyclic core structure. Org. Lett., 4, 4483–4486 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Newman, M. S., Sankaran, V., and Olson, D. R., Phenolic and ketonic tautomers in polycyclic aromatic hydrocarbons. J. Am. Chem. Soc., 98, 3237–3242 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Nishide, K., Ohsugi, S., Miyamoto, T., Kumar, K., and Node, M., Development of odorless thiols and sulfides and their applications to organic synthesis. Monstshefte fûr chime., 135, 189–200 (2004).

    CAS  Google Scholar 

  • Node, M., Kumar, K., Nishide, K., Ohsugi, S-. I., and Miyamoto, T., Odorless substitutes for foul-smelling thiols: syntheses and applications. Tetrahedron Lett., 42, 9207–9210 (2001).

    Article  CAS  Google Scholar 

  • Renaud, J., Bischoff, S. F., Buhl, T., Floersheim, P., Fournier, B., Geiser, M., Halleux, C., Kallen, J., Keller, H., and Ramage, P., Selective estrogen receptor modulators with conformationally restricted side chains. Synthesis and structure-activity relationship of ERα-Selective tetrahydroisoquinoline ligands. J. Med. Chem., 48, 364–379 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Weissman, S. A. and Zewge, D., Recent advances in ether dealkylation. Tetrahedron, 61, 7833–7863 (2005).

    Article  CAS  Google Scholar 

  • Wuts, P. G. M. and Greene, T. W., Protective Groups in Organic Synthesis, John Wiley & Sons, Hoboken, NJ, pp. 370–382 (2007).

    Google Scholar 

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Correspondence to Junghyun Chae.

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Chae, J. Practical demethylation of aryl methyl ethers using an odorless thiol reagent. Arch. Pharm. Res. 31, 305–309 (2008). https://doi.org/10.1007/s12272-001-1156-y

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  • DOI: https://doi.org/10.1007/s12272-001-1156-y

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