Skip to main content
SpringerLink
Log in

Conversion of 2,4-difluoroaniline to 1,3-difluorobenzene using a continuous-flow reactor

  • Communications
  • Published:
Journal of Flow Chemistry Aims and scope Submit manuscript

Abstract

An expeditious and highly efficient process for the synthesis of 1,3-difluorobenzene via a continuous-flow reactor was developed. The main steps included diazotization of 2,4-difluoroaniline and hydro-de-diazotization of intermediate diazonium salt. The continuous diazotization reactor was operated at 20 °C with a residence time of 10 s, and then diazonium salt reacted with NaH2PO2 at 25 °C with a residence time of 40 min. The total reaction time could be brought down to about 40 min, the yield of 1,3-difluorobenzene reached 90%, and the throughput of 2,4-difluoroaniline was 245 g/h.

á…Ÿ

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

Scheme 1
Scheme 2
Scheme 3
Fig. 1
Scheme 4
Fig. 2

References

  1. Bumagin NA, Zelenkovskii VM, Kletskov AV, Petkevich SK, Dikusar EA, Potkin VI (2016). Russ J Gen Chem 86:68–81

    Article  CAS  Google Scholar 

  2. Wang JX (2006). Chin J Mod Appl Pharm 23:35–37

    Google Scholar 

  3. Qiao LJ (2007). Orano-fluorine Industry 1:41–47

    Google Scholar 

  4. Pauluth D, Tarumi K (2004). J Mater Chem 14:1219–1227

    Article  CAS  Google Scholar 

  5. Nobori T WO 01081274, 2001.

    Google Scholar 

  6. Janmanchi KM, Dolbier WR (2008). Org Process Res Dev 12:349–354

    Article  CAS  Google Scholar 

  7. Milner DJ (1992). Synth Commun 22:73–82

    Article  CAS  Google Scholar 

  8. Yu ZQ; Liu JM; Su WK CN 106242939, 2016.

    Google Scholar 

  9. Tokemu (1991). Product, K. K. JP 9134944

  10. Mercier; Claude; Scott; Graham, V. US 0663379, 1995.

  11. Wedlich RC (2001). Chem Eng Prog 97:60–61

    CAS  Google Scholar 

  12. Partington S, Waldram S (2002). Process Saf Environ Prot 80:33–39

    Article  CAS  Google Scholar 

  13. Sandmeyer T (1884). Ber Dtsch Chem Ges 17:1633–1635

    Article  Google Scholar 

  14. Roglans A, Pla-Quintana A, Moreno-Man͂as (2006). M Chem Rev 106:4622–4643

    Article  CAS  Google Scholar 

  15. Mo F, Dong G, Zhang Y, Wang J (2013). Org Biomol Chem 11:1582–1593

    Article  CAS  PubMed  Google Scholar 

  16. Newman SG, Jensen KF (2013). Green Chem 15:1456–1472

    Article  CAS  Google Scholar 

  17. Browne DL, Pastre JC (2013). Org Process Res Dev 17:1192–1208

    Article  CAS  Google Scholar 

  18. Jensen KF, Reizman BJ, Newman SG (2014). Lab Chip 14:3206–3212

    Article  CAS  PubMed  Google Scholar 

  19. Jense AB, Lindhard AT (2014). J Org Chem 79:1174–1183

    Article  CAS  Google Scholar 

  20. Gutmann B, Cantillo D, Kappe CO (2015). Angew Chem Int Ed 54:6688–6728

    Article  CAS  Google Scholar 

  21. Nagaki A, Nakahara YC (2016). Org Process Res Dev 20:1377–1382

    Article  CAS  Google Scholar 

  22. Lidia CA, Carles RE (2016). ACS Catal 6:7647–76651

    Article  CAS  Google Scholar 

  23. Goldbach M, Danieli E, Perlo J (2016). Tetrahedron Lett 57:122–125

    Article  CAS  Google Scholar 

  24. Borukhova S, Noël T, Methen B (2016). Green Chem 18:4947–4953

    Article  CAS  Google Scholar 

  25. Laudadio G, Gemoets HPL, Noël T, Hessel V (2017). J Org Chem 82:11735–11741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Vega JA, Alonso JM (2017). Org Lett 19:938–941

    Article  CAS  PubMed  Google Scholar 

  27. Chen YS, Hone CA, Kappe CO (2017). Org Process Res Dev 21:1080–1087

    Article  CAS  Google Scholar 

  28. Zhang L, Hessel V, Peng J (2018). Chem Eng J 332:131–139

    Article  CAS  Google Scholar 

  29. Hessel V (2009). Chem Eng Technol 32:1655–1681

    Article  CAS  Google Scholar 

  30. Wahab B, Ellames G, Passey S, Watts P (2010). Tetrahedron 66:3861–3865

    Article  CAS  Google Scholar 

  31. Riva E, Gagliardi S, Mazzoni C, Passarella D, Rencurosi A, Vigo D (2010). Tetrahedron 66:3242–3247

    Article  CAS  Google Scholar 

  32. Wegner J, Ceylan S, Kirschning A (2012). Adv Synth Catal 354:17–57

    Article  CAS  Google Scholar 

  33. Wiles C, Watts P (2012). Green Chem 14:38–54

    Article  CAS  Google Scholar 

  34. Cooper CGF, Lee ER (2012). Org Process Res Dev 16:1090–1097

    Article  CAS  Google Scholar 

  35. Patel D, Mehrvar M (2013). Chem Eng Res Des 91:1223–1234

    Article  CAS  Google Scholar 

  36. Wiles C, Watts P (2014). Green Chem 16:55–62

    Article  CAS  Google Scholar 

  37. Su Y, Hessel V, Noël T (2015). AIChE J 61:2215–2227

    Article  CAS  Google Scholar 

  38. Wootton RCR, Fortt R, de Mello AJ (2002). Lab Chip 2:5–7

    Article  CAS  PubMed  Google Scholar 

  39. Malet-Sanz B, Madrzak J, Ley SV, Baxendale IR (2010). Org Biomol Chem 8:5324–5332

    Article  CAS  PubMed  Google Scholar 

  40. Mueller STR, Wirth T (2015). ChemSusChem 8:245–250

    Article  CAS  Google Scholar 

  41. Deadman BJ, Collins SG, Maguire AR (2015). Chem Eur J 21:2298–2308

    Article  CAS  PubMed  Google Scholar 

  42. Yu ZQ, Lv YW, Yu CM (2012). Org Process Res Dev 16:1669–1672

    Article  CAS  Google Scholar 

  43. Yu ZQ, Lv YW, Yu CM, Su WK (2013). Tetrahedron Lett 54:1261–1263

    Article  CAS  Google Scholar 

  44. Yu ZQ, Tong G, Xie XX, Zhou PC, Lv YW, Su WK (2015). Org Process Res Dev 19:892–896

    Article  CAS  Google Scholar 

  45. Yu ZQ, Xie XX, Dong H, Liu JM, Su WK (2016). Org Process Res Dev 20:774–779

    Article  CAS  Google Scholar 

  46. Yu ZQ, Dong H, Xie XX, Liu JM, Su WK (2016). Org Process Res Dev 20:2116–2123

    Article  CAS  Google Scholar 

  47. Yu ZQ, Ye X, Xu QL, Xie XX, Dong H, Su WK (2017). Org Process Res Dev 21:1644–1652

    Article  CAS  Google Scholar 

  48. Hogan PJ, Cox BG (2009). Org Process Res Dev 13:875–879

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are grateful to the Public Projects of Zhejiang Province (No. 2016C33071) and the National Natural Science Foundation of China (No. 21406203) for financial support.

Author information

Authors and Affiliations

  1. National Engineering Research Center for Process Development of Active Pharmaceutical Ingredients, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, 310014, People’s Republic of China

    Zhiqun Yu, Guangjie Lu, Shitian Xie & Weike Su

  2. Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, 310014, People’s Republic of China

    Jianyang Chen & Weike Su

Authors
  1. Zhiqun Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guangjie Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jianyang Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shitian Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Weike Su
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Weike Su.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yu, Z., Lu, G., Chen, J. et al. Conversion of 2,4-difluoroaniline to 1,3-difluorobenzene using a continuous-flow reactor. J Flow Chem 8, 51–57 (2018). https://doi.org/10.1007/s41981-018-0009-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s41981-018-0009-2

Keywords

Search

Navigation