Skip to main content
SpringerLink
Log in

New synthesis of 4-methoxyisophthalic acid

  • Published:
Russian Journal of Organic Chemistry Aims and scope Submit manuscript

Abstract

A new synthetic route to 4-methoxyisophthalic acid, the key intermediate in the synthesis of Picotamide, is reported. The new protocol starts from commercially available and cheap 4-methylphenol and includes four steps: esterification, Fries rearrangement, methylation, and oxidation; the overall yield is 49%. Unlike the traditional Blanc chloromethylation/oxidation scheme, the proposed procedure avoids using volatile and corrosive hydrochloric acid.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Milani, M., Longoni, A., and Maderna, M., Br. J. Clin. Pharmacol., 1996, vol. 42, p. 782.

    Article  CAS  Google Scholar 

  2. Modesti, P.A., Cardiovasc. Drug Rev., 1995, vol. 13, p. 353.

    Article  CAS  Google Scholar 

  3. Celestini, A. and Violi, F., Vasc. Health Risk Manage., 2007, vol. 3, p. 93.

    CAS  Google Scholar 

  4. Sartori, E., Camy, F., Teulon, J.M., Caussade, F., Virone-Oddos, A., and Cloarec, A., Eur. J. Med. Chem., 1993, vol. 28, p. 625.

    Article  CAS  Google Scholar 

  5. Liu, X.J., Shao, Y.L., Wang, C., He, X., Si, H.Q., and Wang, S.J., Chin. J. Med. Chem., 2007, vol. 17, p. 354.

    CAS  Google Scholar 

  6. Liu, X.J., Shi, X.X., Zhong, Y.L., Liu, N., Liu, K., Bioorg. Med. Chem. Lett., 2012, vol. 22, p. 6591.

    Article  CAS  Google Scholar 

  7. Deng, N., Liu, X.J., Shi, C.L., Zhang, F.X., and Liu, L.Z., Chin. J. Med. Chem., 2012, vol. 22, p. 191.

    Google Scholar 

  8. Liu, X.J., He, X., Shi, C.L., Meng, J., Shao, Y.L., Si, H.Q., and Hu, T., Chin. Chem. Lett., 2011, vol. 22, p. 1139.

    CAS  Google Scholar 

  9. Sprengling, G.R. and Freeman, J.H., J. Am. Chem. Soc., 1950, vol. 72, p. 1982.

    Article  CAS  Google Scholar 

  10. Gray, R. and Bonner, J., J. Am. Chem. Soc., 1948, vol. 70, p. 1249.

    Article  CAS  Google Scholar 

  11. Shaikh, M.H., Subhedar, D.D., Khedkar, V.M., Jha, P.C., Khan, F.A.K., Sangshetti, J.N., and Shingate, B.B., Chin. Chem. Lett., 2016, vol. 27, p. 1058.

    Article  CAS  Google Scholar 

  12. Buchwald, S.L., Watson, B.T., Lum, R.T., and Nugent, W.A., J. Am. Chem. Soc., 1987, vol. 109, p. 7137.

    Article  Google Scholar 

  13. Rao, K.V.J. and Row, L.R., J. Org. Chem., 1960, vol. 25, p. 981.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin, 300384, P.R. China

    X. J. Liu, Y. N. Yan, X. Li & X. G. Liu

  2. School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, P.R. China

    S. Q. Wang

Authors
  1. X. J. Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y. N. Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Q. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. X. Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. X. G. Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to X. J. Liu or X. G. Liu.

Additional information

The text was submitted by the authors in English.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, X.J., Yan, Y.N., Wang, S.Q. et al. New synthesis of 4-methoxyisophthalic acid. Russ J Org Chem 53, 459–461 (2017). https://doi.org/10.1134/S1070428017030241

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1070428017030241

Search

Navigation