화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Journal of Industrial and Engineering Chemistry, Vol.82, 113-121, February, 2020
DOI10.1016/j.jiec.2019.10.002  Export Citation
Microfluidic continuous flow synthesis of 1,5-ditosyl-1,5-diazocane-3,7-dione using response surface methodology
Yang Zou, Tao Zhang, Guannan Wang, Mengwen Zhou, Yabo Xiong, Shaoyun Huang, Houbin Li†, and Xinghai Liu†
  • School of Printing and Packaging, Wuhan University, Wuhan, 430079, China
E-mail:,
3,3,7,7-tetrakis(difluoroamino) octahydro-1,5-dinitro-1,5-diazocine (HNFX) is a high-density energetic oxidizer with four difluoroamino groups (-NF2). In this study, 1,5-ditosyl-1,5-diazocane-3,7-dione, as an important intermediate for synthesis of HNFX, was successfully synthesized using Swern oxidation in a traditional batch reactor and a continuous flow microreactor, respectively. 1,5-dotosyl-1,5-diazocane-3,7-dione was characterized by HPLC, FTIR, 1H NMR, 13C NMR, Mass spectrometry, and X-ray crystal diffraction. Compared with the traditional batch reactor, the microreactor showed several advantages, including less reaction time, milder reaction temperature, higher yield and selectivity for 1,5-ditosyl-1,5-diazocane-3,7-dione. Moreover, the microreactor could ensure the safer and large-scale industrial production of 1,5-ditosyl-1,5-diazocane-3,7-dione. However, some solids produced in Swern oxidation which might block the channels (diameter of 0.3 mm) in the microreactor. To overcome the challenges, the experimental device was modified to suit for Swern oxidation, contributing to wider application of the microreactor. Besides, response surface methodology (RSM) was introduced and an appropriate mathematical model was built to optimize experimental conditions. The optimum experimental parameters were recommended as 7.8 °C for the reaction temperature, 7.7 mL/min for the flow rate, and 6% for the concentration of oxalyl chloride. The actual yield of 1,5-ditosyl-1,5-diazocane-3,7-dione was 89.7%, which was in great agreement with the highest predicted yield (90.1%).
Keywords:High-density energetic oxidizers;1,5-Ditosyl-1,5-diazocane-3,7-dione;HNFX;Continuous;flow microreactor;Response surface methodology
  1. Gayathri S, Reshmi S, Polym. Adv. Technol., 28, 1539 (2017)
  2. Cheng T, Des. Monomers Polym., 22, 54 (2019)
  3. Trache D, Klapotke TM, Maiz L, Abd-Elghany M, DeLuca LT, Green Chem., 19, 4711 (2017)
  4. Kumar P, Def. Technol., 14, 661 (2018)
  5. Ye C, Gao H, Shreeve JNM, J. Fluorine Chem., 128, 1410 (2007)
  6. Degirmenbasi N, Peralta-Inga Z, Olgun U, Gocmez H, Kalyon DM, J. Energ. Mater., 24, 103 (2006)
  7. Peralta-Inga Z, Degirmenbasi N, Olgun U, Gocmez H, Kalyon DM, J. Energ. Mater., 24, 69 (2006)
  8. Weck PF, Gobin C, Kim E, Pravica MG, J. Raman Spectrosc., 40, 964 (2009)
  9. Chapman RD, Gilardi RD, Welker MF, Kreutzberger CB, J. Org. Chem., 64, 960 (1999)
  10. Chapman RD, Welker MF, Kreutzberger CB, J. Org. Chem., 63, 1566 (1998)
  11. Zou Y, Fei J, Chen L, Dong Q, Li H, Curr. Org. Synth., 16, 398 (2019)
  12. Mancuso AJ, Brownfain DS, Swern D, J. Org. Chem., 44, 4148 (1979)
  13. Mancuso AJH, Swern SLD, J. Org. Chem., 43, 2480 (1978)
  14. Choe J, Lee H, Kim YJ, Lee SM, Song KH, J. Ind. Eng. Chem., 14(1), 66 (2008)
  15. Galy N, Nguyen R, Blach P, Sambou S, Luart D, Len C, J. Ind. Eng. Chem., 51, 312 (2017)
  16. Huang H, du Toit H, Besenhard MO, Ben-Jaber S, Dobson P, Parkin I, Gavriilidis A, Chem. Eng. Sci., 189, 422 (2018)
  17. Tang Z, Kim WS, Yu TK, J. Ind. Eng. Chem., 66, 411 (2018)
  18. Tanimu A, Jaenicke S, Alhooshani K, Chem. Eng. J., 327, 792 (2017)
  19. Suhadolnik L, Pohar A, Novak U, Likozar B, Mihelic A, Ceh M, J. Ind. Eng. Chem., 72, 178 (2019)
  20. Shi HH, Nie KX, Dong B, Long MQ, Xu H, Liu ZC, Chem. Eng. J., 361, 635 (2019)
  21. Suryawanshi PL, Gumfekar SP, Bhanvase BA, Sonawane SH, Pimplapure MS, Chem. Eng. Sci., 189, 431 (2018)
  22. McQuade DT, Seeberger PH, J. Org. Chem., 78, 6384 (2013)
  23. Yoshida J, Takahashi Y, Nagaki A, Chem. Commun., 49, 9896 (2013)
  24. Bleie O, Roberto MF, Dearing TI, Branham CW, Kvalheim OM, Marquardt BJ, J. Flow Chem., 5, 183 (2015)
  25. Kawaguchi T, Miyata H, Ataka K, Mae K, Yoshida J, Angew. Chem.-Int. Edit., 44, 2413 (2005)
  26. Nieuwland PJ, Koch K, van Harskamp N, Wehrens R, van Hest JCM, Rutjes FPJT, Chem. Asian J., 5, 799 (2010)
  27. Amiri S, Shakeri A, Sohrabi MR, Khalajzadeh S, Ghasemi E, Food Chem., 271, 762 (2019)
  28. Hou F, Mu T, Ma M, Blecker C, Food Chem., 278, 136 (2019)
  29. Taghipour T, Karimipour G, Ghaedi M, Asfaram A, Ultrason. Sonochem., 41, 389 (2018)
  30. Sadeghfar F, Ghaedi M, Asfaram A, Jannesar R, Javadian H, Pezeshkpour V, J. Ind. Eng. Chem., 65, 349 (2018)
  31. Mazaheri H, Ghaedi M, Azqhandi MHA, Asfaram A, Phys. Chem. Chem. Phys., 19, 11299 (2017)
  32. Dil EA, Ghaedi M, Asfaram A, Mehrabi F, Sadeghfar F, J. Ind. Eng. Chem., 74, 55 (2019)
  33. Behbahani ES, Ghaedi M, Asfaram A, Eur. Polym. J., 118, 661 (2019)
  34. Asfaram A, Ghaedi M, Dashtian K, Ghezelbash GR, ACS Sustain. Chem. Eng., 6, 4549 (2018)
  35. Asfaram A, Ghaedi M, Agarwal S, Tyagi I, Gupta VK, RSC Adv., 5, 18438 (2015)
  36. Asfaram A, Sadeghi H, Goudarzi A, Kokhdan EP, Salehpour Z, Analyst, 144, 1923 (2019)
  37. Asfaram A, Ghaedi M, Javadian H, Goudarzi A, Ultrason. Sonochem., 47, 1 (2018)
  38. Chapman RD, Gilardi RD, Welker MF, Kreutzberger CB, J. Org. Chem., 64, 960 (1999)
  39. Zhu L, Xu X, Zheng F, Turk. J. Chem., 42, 75 (2018)