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Continuous diazotization of aromatic amines with high acid and sodium nitrite concentrations in microreactors

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Abstract

We design a new continuous diazotization microreaction process in which concentrated acid and sodium nitrite solutions are used. We form oil in water (O/W) microdroplets by mixing amine with sodium nitrite aqueous solution, which react with mineral acid to make the diazotization. In this way, the formed particles are dispersed in the aqueous phase, which can flow with the main stream, and consequently are consumed. Then the fluid can smoothly flow without clogging in the microchannels and we can achieve continuous operation. We use aniline, o-methylaniline, m-methylaniline, and o-ethylaniline as the raw materials, 6 M HCl and 6.5 M H2SO4 as the acid as well as sodium nitrite to demonstrate the feasibility. The resulting diazonium salts are converted to iodo-substitute aromatic compounds to measure the yield. The results show that, SIMM-V2 micromixer is efficient to form the emulsion. Mixing the microdroplets with acid in a co-axial flow way can prevent clogging. In hydrochloric acid medium, high reaction yield can be obtained when the reaction temperature is 4 °C and the residence time is 13–15 s. In sulfuric acid medium, high conversion of aromatic amine of up to 99% and yield of approximately 90% can be achieved at the reaction temperature of 9 °C and the residence time of 14–16 s. This process provides efficient continuous diazotization reactions using concentrated acid and sodium nitrite solutions, minimizing the production of waste water.

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References

  1. Wu YB, Lu GP, Zhou BJ, Bu MJ, Wan L, Cai C (2016) Visible-light-initiated difluoromethylation of arene diazonium tetrafluoroborates. Chem. Commun. 52(35):5965–5968

    Article  CAS  Google Scholar 

  2. Jiang HZ, Chen YR, Chen B, Xu H, Wan W, Deng HM, Ma KS, Wu SX, Hao J (2017) Ag-initiated gem-Difluoromethylenation of the nitrogen Center of Arenediazonium Salts to gem-Difluoromethylene azo compounds. Org. Lett. 19(9):2406–2409

    Article  CAS  Google Scholar 

  3. Roglans A, Pla-Quintana A, Moreno-Manas M (2006) Diazonium salts as substrates in palladium-catalyzed cross-coupling reactions. Chem. Rev. 106(11):4622–4643

    Article  CAS  Google Scholar 

  4. Akwi FM, Watts P (2016) The in situ generation and reactive quench of diazonium compounds in the synthesis of azo compounds in microreactors. Beilstein J. Org. Chem. 12(1):1987–2004

    Article  CAS  Google Scholar 

  5. Fortt R, Wootton RCR, de Mello AJ (2003) Continuous-flow generation of anhydrous Diazonium species: monolithic microfluidic reactors for the chemistry of unstable intermediates. Org. Process. Res. Dev. 7(5):762–768

    Article  CAS  Google Scholar 

  6. Mo FY, Dong GB, Zhang Y, Wang JB (2013) Recent applications of arene diazonium salts in organic synthesis. Org Biomol Chem 11(10):1582–1593

    Article  CAS  Google Scholar 

  7. Koziakov D, Wu GJ, von Wangelin AJ (2018) Aromatic substitutions of arenediazonium salts via metal catalysis, single electron transfer, and weak base mediation. Org Biomol Chem 16(27):4942–4953

    Article  CAS  Google Scholar 

  8. Yu ZQ, Ye X, Xu QL, Xie XX, Dong H, Su WK (2017) A fully continuous-flow process for the synthesis of p-cresol: impurity analysis and process optimization. Org. Process. Res. Dev. 21(10):1644–1652

    Article  CAS  Google Scholar 

  9. Gutmann B, Cantillo D, Kappe CO (2015) Continuous-flow technology--a tool for the safe manufacturing of active pharmaceutical ingredients. Angew Chem Int Edit 54(23):6688–6728

    Article  CAS  Google Scholar 

  10. Malet-Sanz L, Madrzak J, Ley SV, Baxendale IR (2010) Preparation of arylsulfonyl chlorides by chlorosulfonylation of in situ generated diazonium salts using a continuous flow reactor. Org Biomol Chem 8(23):5324–5332

    Article  CAS  Google Scholar 

  11. Oger N, Le Grognec E, Felpin FX (2015) Handling Diazonium salts in flow for organic and material chemistry. Org Chem Front 46(29):590–614

    Article  Google Scholar 

  12. Yu ZQ, Tong G, Xie XX, Zhou PC, Lv YW, Su WK (2015) Continuous-flow process for the synthesis of 2-Ethylphenylhydrazine hydrochloride. Org. Process. Res. Dev. 19(7):892–896

    Article  CAS  Google Scholar 

  13. Chernyak N, Buchwald SL (2012) Continuous-flow synthesis of Monoarylated acetaldehydes using Aryldiazonium salts. J. Am. Chem. Soc. 134(30):12466–12469

    Article  CAS  Google Scholar 

  14. Li B, Widlicka D, Boucher S, Hayward C, Lucas J, Murray JC, O'Neil BT, Pfisterer D, Samp L, VanAlsten J, Xiang YQ, Young J (2012) Telescoped flow process for the syntheses of N-aryl Pyrazoles. Org. Process. Res. Dev. 16(12):2031–2035

    Article  CAS  Google Scholar 

  15. Yu ZQ, Lv YW, Yu CM, Su WK (2013) Continuous flow reactor for Balz-Schiemann reaction: a new procedure for the preparation of aromatic fluorides. Tetrahedron Lett. 54(10):1261–1263

    Article  CAS  Google Scholar 

  16. Wootton RCR, Fortt R, de Mello AJ (2002) On-chip generation and reaction of unstable intermediates-monolithic nanoreactors for diazonium chemistry: azo dyes. Lab Chip 2(1):5–7

    Article  CAS  Google Scholar 

  17. Wu H, Wang CQ, Zeng CF, Zhang LX (2013) Preparation of barium sulfate nanoparticles in an Interdigital Channel configuration micromixer SIMM-V2. In Eng Chem Res 52(15):5313–5320

    Article  CAS  Google Scholar 

  18. Khaligh NG (2017) Telescopic synthesis of azo compounds via, stable arenediazonium bis ( trifluoromethane ) sulfonimide salts by using tert-butyl nitrite. Dyes Pigments 139:556–560

    Article  CAS  Google Scholar 

  19. Chamoulaud G (2007) Belanger D. spontaneous derivatization of a copper electrode with in situ generated Diazonium cations in aprotic and aqueous media. J. Phys. Chem. C 111(20):7501–7507

    Article  CAS  Google Scholar 

  20. Erickson AE, Spoerri PE (1946) Syntheses in the pyrazine series; the preparation and properties of the pyrazyl halides. J. Am. Chem. Soc. 68(3):400–402

    Article  CAS  Google Scholar 

  21. Titinchi SJJ, Kamounah FS, Abbo HS, Hammerich O (2008) The synthesis of mono- and diacetyl-9H-fluorenes. Reactivity and selectivity in the Lewis acid catalyzed Friedel-crafts acetylation of 9H-fluorene. Arkivoc 2008(13):91–105

    Article  Google Scholar 

  22. Chen J, Lu MM, Liu B, Chen Z, Li QB, Tao LJ, Hu GY (2012) Synthesis and structure-activity relationship of 5-substituent-2(1H)-pyridone derivatives as anti-fibrosis agents. Bioorg. Med. Chem. Lett. 22(6):2300–2302

    Article  CAS  Google Scholar 

  23. Krasnokutskaya EA, Semenischeva NI, Filimonov VD, Knochel P (2007) A new, one-step, effective protocol for the iodination of aromatic and heterocyclic compounds via aprotic diazotization of amines. Synthesis-Stuttgart 38(17):81–84

    Article  Google Scholar 

  24. Piatkivskyi A, Osburn S, Jaderberg K, Grzetic J, Steill JD, Oomens J, Zhao JF, Lau JKC, Verkerk UH, Hopkinson AC, Siu KWM, Ryzhov V (2013) Structure and reactivity of the Distonic and aromatic radical cations of tryptophan. J Am Soc Mass Spectr 24(4):513–523

    Article  CAS  Google Scholar 

  25. Hajipour AR, Seddighi M (2011) Application of [Hcpy]HSO4 Bronsted acidic ionic liquid for the synthesis of aryl iodides from aromatic amines. Org Prep and Proced Int 43(3):292–296

    Article  CAS  Google Scholar 

  26. Eshghi H, Bakavoli M, Ghasemzadeh M, Seyedi SM (2015) Ionic liquids bis(2-N-methylimidazoliumethyl)ether dichloroiodate/dibromochlorate as an efficient halogenating reagent for the synthesis of α-haloketones. Res Chem Intermediat 41(3):1673–1682

    Article  CAS  Google Scholar 

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Acknowledgements

We are grateful for financial support from the National Science and Technology Support Program of China (2015BAD15B07), and Priority Academic Program Development of Jiangsu Higher Education Institutions.

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Authors and Affiliations

  1. State Key Laboratory of Materials-Oriented Chemical Engineering and College of Chemical Engineering, Nanjing Tech University, Nanjing, 210009, People’s Republic of China

    Yang Liu, Chongqing Wang & Lixiong Zhang

  2. College of Mechanical and Power Engineering, Nanjing Tech University, No. 5 Xin Mofan Rd, Nanjing, 210009, People’s Republic of China

    Changfeng Zeng

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  1. Yang Liu
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  2. Changfeng Zeng
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  4. Lixiong Zhang
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Correspondence to Lixiong Zhang.

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Liu, Y., Zeng, C., Wang, C. et al. Continuous diazotization of aromatic amines with high acid and sodium nitrite concentrations in microreactors. J Flow Chem 8, 139–146 (2018). https://doi.org/10.1007/s41981-018-0018-1

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  • DOI: https://doi.org/10.1007/s41981-018-0018-1

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