Improving the reaction efficiency of condensation amidation of piperazine with benzoic acid based on kinetics study in microreactors

Journal of Flow Chemistry - Tập 11 - Trang 855-866 - 2021
Qilin Xu1, Shuqing Zhang2, Jinyang Zhao2, Zhikuo Wang2, Linchang Liu3, Pengcheng Zhou3, Zhiqun Yu2, Weike Su1,2
1Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, People’s Republic of China
2National 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, People’s Republic of China
3Zhejiang Tiannuo Pharmaceutical Technology Co., Ltd., Huzhou, People’s Republic of China

Tóm tắt

Here we developed a continuous flow microreactor system to synthesis N-benzoylpiperazine, which is an important intermediate of novel nootropic Sunifiram. And the kinetics of the condensation amidation of piperazine and benzoic acid using HATU as coupling reagent was revealed in microreactor. A kinetic model was established, all the reactions kinetics parameters, including the reaction order of each reactant, rate constants, pre-exponential factors and activation energies were acquired. With this model the selectivity vs. reaction temperature/molar flow ratio were obtained to help understand this kind of reaction and further optimize operating conditions. Under the condition of using equivalent piperazine, 95.6% of selectivity and 91.2% of yield were obtained in microreactor with 50 s. To further expand the scope of carboxylic acid, cyclopropanecarboxylic acid was tried as acylating agent, and 92.8% of selectivity and 86.1% of yield were obtained in microreactor.

Tài liệu tham khảo

Lundberg H, Tinnis F, Selander N, Adolfsson H (2014) Catalytic amide formation from non-activated carboxylic acids and amines. Chem. Soc. Rev. 43(8):2714–2742. https://doi.org/10.1039/c3cs60345h Du Y, Barber T, Lim SE, Rzepa HS, Baxendale IR, Whiting A (2019) A solid-supported arylboronic acid catalyst for direct amidation. Chem. Commun. 55(20):2916–2919. https://doi.org/10.1039/c8cc09913h Lubberink M, Schnepel C, Citoler J, Derrington SR, Finnigan W, Hayes MA, Turner NJ, Flitsch SL (2020) Biocatalytic monoacylation of symmetrical diamines and its application to the synthesis of pharmaceutically relevant amides. ACS Catal. 10(17):10005–10009. https://doi.org/10.1021/acscatal.0c02228 Bandgar BP, Pandit SS (2003) Highly rapid and direct synthesis of monoacylated piperazine derivatives from carboxylic acids under mild conditions. Tetrahedron Lett. 44(19):3855–3858. https://doi.org/10.1016/s0040-4039(03)00684-1 Zhang Z, Yin Z, Meanwell NA, Kadow JF, Wang T (2003) Selective monoacylation of symmetrical diamines via prior complexation with boron. Org. Lett. 5:3399–3402. https://doi.org/10.1002/chin.200403043 Verma SK, Acharya BN, Kaushik MP (2010) Imidazole-catalyzed monoacylation of symmetrical diamines. Org. Lett. 12:4232–4235. https://doi.org/10.1021/ol101604q Verma SK, Ghorpade R, Pratap A, Kaushik MP (2012) CDI-mediated monoacylation of symmetrical diamines and selective acylation of primary amines of unsymmetrical diamines. Green Chem. 14(2):326–329. https://doi.org/10.1039/c1gc16314k Jursic BS, Zdravkovski Z (1993) A simple preparation of amides from acids and amines by heating of their mixture. Synth. Commun. 23(19):2761–2770. https://doi.org/10.1080/00397919308013807 Gooßen L, Ohlmann D, Lange P (2009) The thermal amidation of carboxylic acids revisited. Synthesis 1:160–164. https://doi.org/10.1055/s-0028-1083277 Varma RS (1999) Solvent-free organic syntheses using supported reagents and microwave irradiation. Green Chem. 1:43–55. https://doi.org/10.1039/A808223E Perreux L, Loupy A, Volatron F (2002) Solvent-free preparation of amides from acids and primary amines under microwave irradiation. Tetrahedron 58:2155–2162. https://doi.org/10.1016/S0040-4020(02)00085-6 Dunetz JR, Magano J, Weisenburger GA (2016) Large-scale applications of amide coupling reagents for the synthesis of pharmaceuticals. Org. Process. Res. Dev. 20(2):140–177. https://doi.org/10.1021/op500305s Carey JS, Laffan D, Thomson C, Williams MT (2006) Analysis of the reactions used for the preparation of drug candidate molecules. Org. Biomol. Chem. 4(12):2337–2347. https://doi.org/10.1039/b602413k Hartman RL, McMullen JP, Jensen KF (2011) Deciding whether to go with the flow: evaluating the merits of flow reactors for synthesis. Angew. Chem. Int. Ed. 50(33):7502–7519. https://doi.org/10.1002/anie.201004637 Gutmann B, Cantillo D, Kappe CO (2015) Continuous-flow technology-a tool for the safe manufacturing of active pharmaceutical ingredients. Angew. Chem. Int. Ed. 54(23):6688–6728. https://doi.org/10.1002/anie.201409318 Gemoets HP, Su YH, Shang M, Hessel V, Luque R, Noel T (2016) Liquid phase oxidation chemistry in continuous-flow microreactors. Chem. Soc. Rev. 45(1):83–117. https://doi.org/10.1039/c5cs00447k Guidi M, Seeberger PH, Gilmore K (2020) How to approach flow chemistry. Chem. Soc. Rev. 49(24):8910–8932. https://doi.org/10.1039/c9cs00832b Sui JS, Yan JY, Liu D, Wang K, Luo GS (2020) Continuous synthesis of nanocrystals via flow chemistry technology. Small 16(16):1902828–1902850. https://doi.org/10.1002/smll.201902828 Liu YY, Chen GW, Yue J (2020) Manipulation of gas-liquid-liquid systems in continuous flow microreactors for efficient reaction processes. J. Flow. Chem. 10(1):103–121. https://doi.org/10.1007/s41981-019-00062-9 Yoshida J, Kim H, Nagaki A (2011) Green and sustainable chemical synthesis using flow microreactors. ChemSusChem 4(3):331–340. https://doi.org/10.1002/cssc.201000271 Baumann M, Moody TS, Smyth M, Wharry S (2020) A perspective on continuous flow chemistry in the pharmaceutical industry. Org. Process. Res. Dev. 24(10):1802–1813. https://doi.org/10.1021/acs.oprd.9b00524 Qiu L, Wang K, Zhu S, Lu YC, Luo GS (2016) Kinetics study of acrylic acid polymerization with a microreactor platform. Chem. Eng. J. 284:233–239. https://doi.org/10.1016/j.cej.2015.08.055 Wen ZH, Yang M, Zhao SN, Zhou F, Chen GW (2018) Kinetics study of heterogeneous continuous-flow nitration of trifluoromethoxybenzene. React. Chem. Eng. 3(3):379–387. https://doi.org/10.1039/c7re00182g Rehman A, López Fernández AM, Resul MFMG, Harvey A (2018) Kinetic investigations of styrene carbonate synthesis from styrene oxide and CO2 using a continuous flow tube-in-tube gas-liquid reactor. J. CO2 Util. 24:341–349. https://doi.org/10.1016/j.jcou.2018.02.001 Li GX, Liu S, Dou XY, Wei HL, Shang MJ, Luo ZH, Su YH (2020) Synthesis of adipic acid through oxidation of K/a oil and its kinetic study in a microreactor system. AICHE J. 66(9):16289–16300. https://doi.org/10.1002/aic.16289 Ładosz A, Kuhnle C, Jensen KF (2020) Characterization of reaction enthalpy and kinetics in a microscale flow platform. React. Chem. Eng. 5(11):2115–2122. https://doi.org/10.1039/d0re00304b Yu ZQ, Xu QL, Liu LC, Wu ZK, Huang JJ, Lin JY, Su WK (2020) Dinitration of o-toluic acid in continuous-flow: process optimization and kinetic study. J. Flow. Chem. 10(2):429–436. https://doi.org/10.1007/s41981-020-00078-6 Zhang CY, Zhang JS, Luo GS (2020) Kinetics determination of fast exothermic reactions with infrared thermography in a microreactor. J. Flow. Chem. 10(1):219–226. https://doi.org/10.1007/s41981-019-00071-8 Dong C, Wang K, Zhang JS, Luo GS (2015) Reaction kinetics of cyclohexanone ammoximation over TS-1 catalyst in a microreactor. Chem. Eng. Sci. 126:633–640. https://doi.org/10.1016/j.ces.2015.01.006 Hartman RL, Jensen KF (2009) Microchemical systems for continuous-flow synthesis. Lab. Chip. 9(17):2495–2507. https://doi.org/10.1039/b906343a Wiles C, Watts P (2012) Continuous flow reactors: a perspective. Green Chem. 14(1):38–54. https://doi.org/10.1039/c1gc16022b Jensen KF (2017) Flow chemistry-microreaction technology comes of age. AICHE J. 63(3):858–869. https://doi.org/10.1002/aic.15642 Wang PJ, Wang K, Zhang JS, Luo GS (2015) Kinetic study of reactions of aniline and benzoyl chloride in a microstructured chemical system. AICHE J. 61(11):3804–3811. https://doi.org/10.1002/aic.14891 Zhang H, Yu ZY, Gu T, Xiang L, Shang MJ, Shen C, Su YH, (2020) Continuous synthesis of 5-hydroxymethylfurfural using deep eutectic solvents and its kinetic study in microreactors. Chem. Eng. J. 391. https://doi.org/10.1016/j.cej.2019.123580 Xu QL, Fan HC, Yao HM, Wang DH, Yu HW, Chen BB, Yu ZQ, Su WK (2020) Understanding monoacylation of symmetrical diamines: a kinetic study of acylation reaction of m-phenylenediamine and benzoic anhydride in microreactor. Chem. Eng. J. 398:125584–125593. https://doi.org/10.1016/j.cej.2020.125584 Manetti D, Ghelardini C, Bartolini A, Dei S, Galeotti N, Gualtieri F, Romanelli MN, Teodori E (2000) Molecular simplification of 1,4-diazabicyclo[4.3.0]nonan-9-ones gives piperazine derivatives that maintain high nootropic activity. J. Med. Chem. 43(23):4499–4507. https://doi.org/10.1021/jm000972h Moriguchi S, Tanaka T, Tagashira H, Narahashi T, Fukunaga K (2013) Novel nootropic drug sunifiram improves cognitive deficits via CaM kinase II and protein kinase C activation in olfactory bulbectomized mice. Behav. Brain Res. 242:150–157. https://doi.org/10.1016/j.bbr.2012.12.054 Guandalini L, Martino MV, Di Cesare ML, Bartolucci G, Melani F, Malik R, Dei S, Floriddia E, Manetti D, Orlandi F, Teodori E, Ghelardini C, Romanelli MN (2015) Substituted piperazines as nootropic agents: 2- or 3-phenyl derivatives structurally related to the cognition-enhancer DM235. Bioorg. Med. Chem. Lett. 25(8):1700–1704. https://doi.org/10.1016/j.bmcl.2015.03.009 Martino MV, Guandalini L, Di Cesare ML, Menicatti M, Bartolucci G, Dei S, Manetti D, Teodori E, Ghelardini C, Romanelli MN (2017) Piperazines as nootropic agents: new derivatives of the potent cognition-enhancer DM235 carrying hydrophilic substituents. Bioorg. Med. Chem. 25(6):1795–1803. https://doi.org/10.1016/j.bmc.2017.02.019 Carpino LA (1993) 1-Hydroxy-7-azabenzotriazole. An efficient peptide coupling additive. J. Am. Chem. Soc. 115(10):4397–4398. https://doi.org/10.1021/ja00063a082 Albericio F, Bofill JM, El-Faham A, Kates SA (1998) Use of onium salt-based coupling reagents in peptide synthesis. J. Org. Chem. 63(26):9678–9683. https://doi.org/10.1021/jo980807y Valeur E, Bradley M (2009) Amide bond formation: beyond the myth of coupling reagents. Chem. Soc. Rev. 38(2):606–631. https://doi.org/10.1039/b701677h Wilson KL, Murray J, Jamieson C, Watson AJB (2018) Cyrene as a bio-based solvent for HATU mediated amide coupling. Org. Biomol. Chem. 16(16):2851–2854. https://doi.org/10.1039/c8ob00653a Lheureux S, Oza AM (2014) Olaparib for the treatment of ovarian cancer. Expert Opin Orphan Drugs 2(5):497–508. https://doi.org/10.1517/21678707.2014.899147 Deeks ED (2015) Olaparib: first global approval. Drugs 75(2):231–240. https://doi.org/10.1007/s40265-015-0345-6