Kinetics Research and Process Development for the Intensification of the Fully Continuous Flow Synthesis of 3-Amino-1-Adamantanol
Corresponding Author
Jiadi Zhou
Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou No.18 Chaowang Road, Hangzhou, 310014 P. R. China
E-mail: [email protected]; [email protected]
Search for more papers by this authorWeilong Zhang
Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou No.18 Chaowang Road, Hangzhou, 310014 P. R. China
Search for more papers by this authorShangkun Bai
Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou No.18 Chaowang Road, Hangzhou, 310014 P. R. China
Search for more papers by this authorYinghui Shao
Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou No.18 Chaowang Road, Hangzhou, 310014 P. R. China
Search for more papers by this authorYuanyuan Tang
Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou No.18 Chaowang Road, Hangzhou, 310014 P. R. China
Search for more papers by this authorMengqian Jing
Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou No.18 Chaowang Road, Hangzhou, 310014 P. R. China
Search for more papers by this authorCorresponding Author
Zhiqun Yu
Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou No.18 Chaowang Road, Hangzhou, 310014 P. R. China
E-mail: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Jiadi Zhou
Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou No.18 Chaowang Road, Hangzhou, 310014 P. R. China
E-mail: [email protected]; [email protected]
Search for more papers by this authorWeilong Zhang
Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou No.18 Chaowang Road, Hangzhou, 310014 P. R. China
Search for more papers by this authorShangkun Bai
Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou No.18 Chaowang Road, Hangzhou, 310014 P. R. China
Search for more papers by this authorYinghui Shao
Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou No.18 Chaowang Road, Hangzhou, 310014 P. R. China
Search for more papers by this authorYuanyuan Tang
Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou No.18 Chaowang Road, Hangzhou, 310014 P. R. China
Search for more papers by this authorMengqian Jing
Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou No.18 Chaowang Road, Hangzhou, 310014 P. R. China
Search for more papers by this authorCorresponding Author
Zhiqun Yu
Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou No.18 Chaowang Road, Hangzhou, 310014 P. R. China
E-mail: [email protected]; [email protected]
Search for more papers by this authorAbstract
3-Amino-1-adamantanol (3AA) is an important intermediate of vildagliptin. In this work, a fully continuous flow synthesis of 3-amino-1-adamantanol has been proposed. Selecting amantadine sulfate (AS) as the starting material, the effects of process parameters were systematically investigated, such as the molar ratio of reactants, the amount of sulfuric acid and reaction temperature. The kinetics of nitration reaction were carried out in both batch and continuous flow processes to explain the relationship between the amount of sulfuric acid and the reaction rate constant. Based on the apparent reaction rate constants and thermodynamic parameters, a fully continuous flow synthesis of 3AA combining nitration, hydrolysis and neutralization reaction has been realized. Compared with the batch method, the reaction time was shortened from 8 h to 36 min, the side reactions were significantly inhibited, and the yield increased from 87.8 % to 95.2 % by continuous flow strategy.
Supporting Information
| Filename | Description |
|---|---|
| ceat70022-sup-0001-SuppMat.docx1.1 MB | Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1D. Kumar, A. Gautam, S. Rohatgi, P. P. Kundu, Int. J. Biol. Macromol. 2022, 208, 82–93. DOI: https://doi.org/10.1016/j.ijbiomac.2022.07.066
- 2J. J. Holst, Diabetes Obes. Metab. 2008, 10 (3), 14–21. DOI: https://doi.org/10.1111/j.1463-1326.2008.00920.x
- 3K. Lian, H. Feng, S. Liu, K. Wang, Q. Liu, L. Deng, G. Wang, Y. Chen, G. Liu, Biosens. Bioelectron. 2022, 203, 114029. DOI: https://doi.org/10.1016/j.bios.2022.114029
- 4Y. Wang, F. Zhang, H. Diao, R. Wu, ACS Catalysis. 2019, 9 (3), 2292–2302. DOI: https://doi.org/10.1021/acscatal.8b05051
- 5C. F. Deacon, Diabetes Obes. Metab. 2011, 13 (1), 7–18. DOI: https://doi.org/10.1111/j.1463-1326.2010.01306.x
- 6M. Zhang, X. Jin, Z. Zhang, B. Li, G. Yang, Biomed. Pharmacother. 2018, 108, 1790–1796. DOI: https://doi.org/10.1016/j.biopha.2018.09.148
- 7M. Castaldi, M. Baratella, I. G. Menegotto, G. Castaldi, G. B. Giovenzana, Tetrahedron Lett. 2017, 58, 3426–3428. DOI: https://doi.org/10.1016/j.tetlet.2017.07.062
- 8V. Rathod, P. Saini, R. Kaur, S. Marimganti, K. J. Ranbhan, Org. Process Res. Dev. 2023, 27 (11), 1880–1899. DOI: https://doi.org/10.1021/acs.oprd.3c00048
- 9A. Donetti, E. Bellora, Synthetic Commun 1973, 3 (2), 165–166. DOI: https://doi.org/10.1080/00397917308062027
- 10G. Asensio, M. E. Gonzalez-Nunez, C. B. Bernardini, R. Mello, W. Adam, J. Am. Chem. Soc. 1993, 115, 7250–7253. DOI: https://doi.org/10.1002/chin.199350113
- 11R. I. Khusnutdinov, N. A. Shchadneva, L. F. Mukhametshina, U. M. Dzhemilev, Russ. J. Org. Chem. 2009, 45, 1137–1142. DOI: https://doi.org/10.1134/s1070428009080041
- 12L. Zhang, L. Jiang, X. Guan, L. Cai, J. Wang, P. Xiang, J. Pan, X. Hu, J. Chem. Res. 2021, 45, 305–309. DOI: https://doi.org/10.1177/1747519820967123
- 13X. N. Hu, Q. Liao, H. Zhang, Y. F. Li, CN 201810093838.8, 2018.
- 14S. M. Zhao, L. Li, S. L. Han, CN201410411933.X, 2014.
- 15Y.-C. Liu, J.-C. Jiang, A.-C. Huang, Y. Tang, Y.-P. Yang, H.-L. Zhou, J. Zhai, Z.-X. Xing, C.-F. Huang, C.-M. Shu, Process Saf. Environ. Prot. 2022, 160, 91–101. DOI: https://doi.org/10.1016/j.psep.2022.02.004
- 16J. Huang, F. Ding, P. Rojsitthisak, F.-S. He, J. Wu, Org. Chem. Front. 2020, 18, 2873–2898. DOI: https://doi.org/10.1039/d0qo00563k
- 17T. Yang, X. Li, S. Deng, X. Qi, H. Cong, H.-G. Cheng, L. Shi, Q. Zhou, L. Zhuang, JACS Au. 2022, 2 (9), 2152–2161. DOI: https://doi.org/10.1021/jacsau.2c00413
- 18V. R. L. J. Bloemendal, M. A. C. H. Janssen, J. C. M. Van Hest, F. P. J. T. Rutjes, React. Chem. Eng. 2020, 5 (7), 1186–1197. DOI: https://doi.org/10.1039/d0re00087f
- 19P. P. De Castro, G. M.F. Batista, G. W. Amarante, T. J. Brocksom, K. T. De Oliveira, Curr. Top. Med. Chem. 2023, 23 (11), 970–989. DOI: https://doi.org/10.2174/1568026623666230331083734
- 20D. L. Hughes, Org. Process Res. Dev. 2020, 24 (10), 1850–1860. DOI: https://doi.org/10.1021/acs.oprd.0c00156
- 21B. Marcus, S. M. Thomas, S. Megan, W. Scott, Org. Process Res. Dev. 2020, 24 (10), 1802–1813. DOI: https://doi.org/10.1021/acs.oprd.9b00524
10.1021/acs.oprd.9b00524 Google Scholar
- 22Y. Wang, L. Ni, J. Wang, F. Xu, J. Jiang, Z. Chen, G. Fu, Y. Pan, Chem. Eng. Process. 2022, 170, 108705. DOI: https://doi.org/10.1016/j.cep.2021.108705
- 23N. Zaquen, M. Rubens, N. Corrigan, J. Xu, P. B. Zetterlund, C. Boyer, T. Junkers, Prog. Polym. Sci. 2020, 107, 101256. DOI: https://doi.org/10.1016/j.progpolymsci.2020.101256
- 24F. Florit, V. Busini, G. Storti, R. Rota, Chem. Eng. J. 2018, 354, 1007–1017. DOI: https://doi.org/10.1016/j.cej.2018.08.044
- 25M. A. Bezerra, V. A. Lemos, D. M. De Oliveira, C. G. Novaes, J. A. Barreto, J. P. S. Alves, U. M. F. D. M. Cerqueira, Q. O. D. Santos, S. A. Araújo, Microchem. J. 2020, 155 (1), 104731. DOI: https://doi.org/10.1016/j.microc.2020.104731
- 26Q. L. Xu, H. C. Fan, H. M. Yao, D. H. Wang, H. W. Yu, B. B. Chen, Z. Q. Yu, W. K. Su, Chem. Eng. J. 2020, 398 (1), 125584. DOI: https://doi.org/10.1016/j.cej.2020.125584
- 27Z. Yu, M. Ren, P. Li, J. Zhou, N. Li, X. Li, H. Fan, Chem. Eng. Sci. 2023, 271, 118565. DOI: https://doi.org/10.1016/j.ces.2023.118565
- 28S. Guo, Z. Yu, C. Yu, Org. Process Res. Dev. 2018, 22 (2), 252–256. DOI: https://doi.org/10.1021/acs.oprd.7b00358
- 29Z. Yu, J. Chen, J. Liu, Z. Wu, W. Su, Org. Process Res. Dev. 2018, 22 (12), 1828–1834. DOI: https://doi.org/10.1021/acs.oprd.8b00362
- 30J. Chen, X. Xie, J. Liu, Z. Yu, W. Su, React. Chem. Eng. 2022, 7 (6), 1247–1275. DOI: https://doi.org/10.1039/D2RE00001F
- 31F. Xu, J. Chen, X. Xie, P. Cheng, Z. Yu, W. Su, Org. Process Res. Dev. 2020, 24 (10), 2252–2259. DOI: https://doi.org/10.1021/acs.oprd.0c00302
- 32X. Xie, S. Xie, H. Yao, X. Ye, Z. Yu, W. Su, React. Chem. Eng. 2019, 4, 927–931. DOI: https://doi.org/10.1039/C9RE00084D
- 33G. A. Olah, H. C. H. Lin, J. Am. Chem. Soc. 1971, 93 (5), 1259–1261. DOI: https://doi.org/10.1021/ja00734a039
- 34H. G. M. Edwards, J. M. C. Turner, V. Fawcett, J. Chem. Soc. 1995, 91, 1439–1443. DOI: https://doi.org/10.1039/FT9959101439
- 35D. Russo, L. Onotri, R. Marotta, R. Andreozzi, I. Di Somma, Chem. Eng. J. 2017, 307, 1076–1083. DOI: https://doi.org/10.1016/j.cej.2016.09.034
- 36J. Song, Y. Cui, L. Sheng, Y. Wang, C. Du, J. Deng, G. Luo, Chem. Eng. Sci. 2022, 247, 117041. DOI: https://doi.org/10.1016/j.ces.2021.117041
- 37L. Li, C. Yao, F. Jiao, M. Han, G. Chen, Chem. Eng. Processing. 2017, 117, 179–185. DOI: https://doi.org/10.1016/j.cep.2017.04.005
- 38I. Di Somma, R. Marotta, R. Andreozzi, V. Caprio, Org. Process Res. Dev. 2012, 16 (12), 2001–2007. DOI: https://doi.org/10.1021/op300043x
- 39R. Andreozzi, M. Canterino, V. Caprio, I. Di Somma, R. Sanchirico, Org. Process Res. Dev. 2006, 10 (6), 1199–1204. DOI: https://doi.org/10.1021/op060148o
- 40K. Miyabe, R. Isogai, J. Chromatogr. A 2011, 1218 (38), 6639–6645. DOI: https://doi.org/10.1016/j.chroma.2011.07.018
- 41R. C. Reid, J. M. Prausnitz, T. K. Sherwood, The Properties of Gases and Liquids, McGraw-Hill, New York 1977.
- 42H. Song, D. Cabooter, Chromatographia 2017, 80, 651–663. DOI: https://doi.org/10.1007/s10337-016-3204-z
- 43W. Schotte, Chem. Eng. J. 1992, 48 (3), 167–172. DOI: https://doi.org/10.1016/0300-9467(92)80032-6
- 44P. R. Cox, A. N. Strachan, Chem. Eng. J. 1972, 4 (3), 253–261. DOI: https://doi.org/10.1016/0300-9467(72)80022-4
- 45G. Li, M. Shang, Y. Song, Y. Su, AIChE J. 2018, 64 (3), 1106–1116. DOI: https://doi.org/10.1002/aic.15973
- 46X. D. Chen, Engineering 2019, 5 (3), 576–579. DOI: https://doi.org/10.1016/j.eng.2018.09.013
- 47S. R. L. Gobert, S. Kuhn, L. Braeken, L. C. J. Thomassen, Org. Process Res. Dev. 2017, 21 (4), 531–542. DOI: https://doi.org/10.1021/acs.oprd.6b00359
- 48R. K. Thakur, C. Vial, K. D. P. Nigam, E. B. Nauman, G. Djelveh, Chem. Eng. Res. Des. 2003, 81 (A7), 787–826. DOI: https://doi.org/10.1205/026387603322302968
- 49M. Regner, K. Östergren, C. Trägårdh, Chem. Eng. Sci. 2006, 61 (18), 6133–6141. DOI: https://doi.org/10.1016/j.ces.2006.05.044
- 50A. Ghanem, T. Lemenand, D. Della Valle, H. Peerhossaini, Chem. Eng. Res. Des. 2014, 92 (2), 205–228. DOI: https://doi.org/10.1016/j.cherd.2013.07.013
- 51D. M. Hobbs, P. D. Swanson, F. J. Muzzio, Chem. Eng. Sci. 1998, 53 (8), 1565–1584. DOI: https://doi.org/10.1016/S0009-2509(97)00132-2
- 52S. Armbruster, O. Cheong, J. Lölsberg, S. Popovic, S. Yüce, M. Wessling, J. Membr. Sci. 2018, 554, 156–163. DOI: https://doi.org/10.1016/j.memsci.2018.02.015
