High-efficiency and safe synthesis of tonalid via two Friedel-Crafts reactions in continuous-flow microreactors

doi:10.1016/j.cjche.2021.09.028

Abstract

Abstract: Tonalid, an important fragrance ingredient with widespread application, was synthesized via two Friedel-Crafts reactions, which were catalyzed by AlCl₃. The traditional tonalid production was conducted in batch stirring tank reactors, suffering from low production capacity and the safety hazard of temperature runaway. To solve these problems, the continuous-flow technologies were developed for the high-efficiency and intrinsically safe synthesis of tonalid in microreactors. Catalyst AlCl₃ was neatly homogenized in proper solvents by forming complex with reactant, which was a necessary step for the continuous synthesis in microreactors. Several reaction conditions, including reactant molar ratio, catalyst concentration, temperature, and microchannel hydrodynamic diameter, were investigated for the two Friedel-Crafts reactions in microreactors. At optimized conditions, the yields of the two Friedel-Crafts reactions were 44.15% and 97.55%, respectively. In comparison with the batch reactors, the reaction times of these two reactions could both be reduced by nearly two thirds in microreactors at the similar yield.

Key words: Microreactor, Continuous synthesis, Process intensification, Tonalid, Friedel-Crafts reaction

摘要： Tonalid, an important fragrance ingredient with widespread application, was synthesized via two Friedel-Crafts reactions, which were catalyzed by AlCl₃. The traditional tonalid production was conducted in batch stirring tank reactors, suffering from low production capacity and the safety hazard of temperature runaway. To solve these problems, the continuous-flow technologies were developed for the high-efficiency and intrinsically safe synthesis of tonalid in microreactors. Catalyst AlCl₃ was neatly homogenized in proper solvents by forming complex with reactant, which was a necessary step for the continuous synthesis in microreactors. Several reaction conditions, including reactant molar ratio, catalyst concentration, temperature, and microchannel hydrodynamic diameter, were investigated for the two Friedel-Crafts reactions in microreactors. At optimized conditions, the yields of the two Friedel-Crafts reactions were 44.15% and 97.55%, respectively. In comparison with the batch reactors, the reaction times of these two reactions could both be reduced by nearly two thirds in microreactors at the similar yield.

关键词: Microreactor, Continuous synthesis, Process intensification, Tonalid, Friedel-Crafts reaction

Yang Han, Yuanyuan Liu, Shiwei Wang, Xuehui Ge, Xiaoda Wang, Ting Qiu. High-efficiency and safe synthesis of tonalid via two Friedel-Crafts reactions in continuous-flow microreactors[J]. Chinese Journal of Chemical Engineering, 2022, 52(12): 126-135.

References

[1] C. Sommer, The role of musk and musk compounds in the fragrance industrySer. Anthropog. Compd. (2004). DOI:10.1007/b14130
[2] C.S. Sell, Chemistry and the sense of smell[M]. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2014
[3] É. Morin, J. Sosoe, M. Raymond, B. Amorelli, R.M. Boden, S.K. Collins, Synthesis of a renewable macrocyclic musk: evaluation of batch, microwave, and continuous flow strategies, Org. Process Res. Dev. 23 (2) (2019) 283–287
[4] A. Lenormand, L. Reyes Méndez, J. Coulomb, Relay-heck cross-coupling between alkenyl halides and unsaturated alcohols in the synthesis of open-chain analogues of musk odorant vulcanolide, Chemistry 27 (36) (2021) 9276–9280
[5] A. Sytniczuk, A. Leszczyńska, A. Kajetanowicz, K. Grela, Preparation of musk-smelling macrocyclic lactones from biomass: Looking for the optimal substrate combination, ChemSusChem 11 (18) (2018) 3157–3166
[6] EIR Institute, Detailed Project Report (DPR) on nitro musk. https://www.eiriindia.org/project-report-handbook-nitro-musk-with-formulation-technology-8431.
[7] L. Xu, Y. Cao, Native musk and synthetic musk ketone strongly induced the growth repression and the apoptosis of cancer cells, BMC Complement Altern Med 16 (1) (2016) 511
[8] Y.P. Gao, G.Y. Li, Y.X. Qin, Y.M. Ji, B.X. Mai, T.C. An, New theoretical insight into indirect photochemical transformation of fragrance nitro-musks: Mechanisms, eco-toxicity and health effects, Environ Int 129 (2019) 68–75
[9] K.M. Taylor, M. Weisskopf, J. Shine, Human exposure to nitro musks and the evaluation of their potential toxicity: an overview, Environ. Heal. 13 (1) (2014) 1–7
[10] C.L. D'Andrea, Psychophysical characterization of musk chemicals, Chem. Senses 1 (3) (1975) 359–369
[11] Homem V, Silva JA, Ratola N, Santos L, Alves A, Long lasting perfume: a review of synthetic musks in WWTPs, J Environ Manage 149 (2015) 168–192
[12] T.F. Wood, E. Heilweil, Process for producing 1,1,3,4,4,6-hexamethyl-1,2,3,4- tetrahydronapthalene (HMT), US Pat., 3856875 (1974).
[13] H. Sato, K. Fujisawa, H. Tojima, S. Yasui, Process for preparing hexamethyltetrahydronaphthalenes, US Pat., 4284818 (1981).
[14] G. Suzukamo, Y. Sakito, Tetrahydronaphthalene derivatives and their production, US Pat., 4767882 (1988).
[15] W.C. Frank, Process for preparing 1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene, US Pat., 4877912[P] (1989).
[16] W.C. Frank, D.M. Miller, Hexamethyltetralin preparations. effect of methyltrioctylammonium chloride on solvent/olefin interdependency, Bull. Chem. Soc. Jpn. 66 (1) (1993) 125–129
[17] A. Madhawan, A. Arora, J. Das, A. Kuila, V. Sharma, Microreactor technology for biodiesel production: A review, Biomass Convers. Biorefinery 8 (2) (2018) 485–496
[18] A. Tanimu, S. Jaenicke, K. Alhooshani, Heterogeneous catalysis in continuous flow microreactors: A review of methods and applications, Chem. Eng. J. 327 (2017) 792–821
[19] B.A. Wilhite, Unconventional microreactor designs for process intensification in the distributed reforming of hydrocarbons: A review of recent developments at Texas A&M University, Curr. Opin. Chem. Eng. 17 (2017) 100–107
[20] X.D. Wang, J.N. Xia, D.Y. Liu, Z.X. Huang, X.H. Ge, S.L. Zhang, T. Qiu, Asymmetric behaviors of interface-stabilized slug pairs in a T-junction microchannel reactor, Chem. Eng. Sci. 240 (2021) 116668
[21] S.Z. Zhang, C.Y. Zhu, H.S. Feng, T.T. Fu, Y.G. Ma, Intensification of gas-liquid two-phase flow and mass transfer in microchannels by sudden expansions, Chem. Eng. Sci. 229 (2021) 116040
[22] M.M. Huang, C.Y. Zhu, T.T. Fu, Y.G. Ma, Enhancement of gas-liquid mass transfer by nanofluids in a microchannel under Taylor flow regime, Int. J. Heat Mass Transf. 176 (2021) 121435
[23] X.D. Wang, Y.M. Wang, F. Li, L. Li, X.H. Ge, S.L. Zhang, T. Qiu, Scale-up of microreactor: Effects of hydrodynamic diameter on liquid-liquid flow and mass transfer, Chem. Eng. Sci. 226 (2020) 115838
[24] X.D. Wang, X. Xu, Q.L. Wang, Z.X. Huang, J.Y. He, T. Qiu, Fatty acid methyl ester synthesis through transesterification of palm oil with methanol in microchannels: Flow pattern and reaction kinetics, Energy Fuels 34 (3) (2020) 3628–3639
[25] G.X. Li, X. Pu, M.J. Shang, L. Zha, Y.H. Su, Intensification of liquid-liquid two-phase mass transfer in a capillary microreactor system, Aiche J. 65 (1) (2019) 334–346
[26] K. Wang, L.T. Li, P. Xie, G.S. Luo, Liquid–liquid microflow reaction engineering, React. Chem. Eng. 2 (5) (2017) 611–627
[27] H.C. Liu, C.Q. Yao, Y.C. Zhao, G.W. Chen, Desorption of carbon dioxide from aqueous MDEA solution in a microchannel reactor, Chem. Eng. J. 307 (2017) 776–784
[28] P. Zhang, C.Q. Yao, H.Y. Ma, N. Jin, X.L. Zhang, H. Lü, Y.C. Zhao, Dynamic changes in gas-liquid mass transfer during Taylor flow in long serpentine square microchannels, Chem. Eng. Sci. 182 (2018) 17–27
[29] C.Y. Zhang, J.S. Zhang, G.S. Luo, Kinetics determination of fast exothermic reactions with infrared thermography in a microreactor, J. Flow Chem. 10 (1) (2020) 219–226
[30] H.L. Zhao, S.E. Liu, M.J. Shang, Y.H. Su, Direct oxidation of benzene to phenol in a microreactor: Process parameters and reaction kinetics study, Chem. Eng. Sci. 246 (2021) 116907
[31] C.S. Lee, C. Vorwerk, N.Y. Azudin, N.A. Ahmad, S.R.A. Shukor, Kinetics modelling of uncatalyzed esterification of acetic anhydride with isoamyl alcohol in a microreactor system, J. Environ. Chem. Eng. 9 (3) (2021) 105219
[32] D. Cantillo, C.O. Kappe, Halogenation of organic compounds using continuous flow and microreactor technology, React. Chem. Eng. 2 (1) (2017) 7–19
[33] G. Laudadio, N.J.W. Straathof, M.D. Lanting, B. Knoops, V. Hessel, T. Noël, An environmentally benign and selective electrochemical oxidation of sulfides and thiols in a continuous-flow microreactor, Green Chem. 19 (17) (2017) 4061–4066
[34] G. Li, S. Liu, X. Dou, H. Wei, M. Shang, Z.H. Luo, Y. Su, Synthesis of adipic acid through oxidation of K/A oil and its kinetic study in a microreactor system, AIChE J. 66 (9) (2020) e16289
[35] D. Russo, G. Tomaiuolo, R. Andreozzi, S. Guido, A.A. Lapkin, I. Di Somma, Heterogeneous benzaldehyde nitration in batch and continuous flow microreactor, Chem. Eng. J. 377 (2019) 120346
[36] S.N. Zhao, C.Q. Yao, Q. Zhang, G.W. Chen, Q. Yuan, Acoustic cavitation and ultrasound-assisted nitration process in ultrasonic microreactors: The effects of channel dimension, solvent properties and temperature, Chem. Eng. J. 374 (2019) 68–78
[37] F.J. Wang, A. Chen, S.D. Ling, J.H. Xu, Continuous-flow diazotization of red base KD hydrochloride suspensions in a microreaction system, React. Chem. Eng. 6 (8) (2021) 1462–1474
[38] Y. Liu, C.F. Zeng, C.Q. Wang, L.X. Zhang, Continuous diazotization of aromatic amines with high acid and sodium nitrite concentrations in microreactors, J. Flow Chem. 8 (3) (2018) 139–146
[39] J.S. Zhang, K. Wang, X.Y. Lin, Y.C. Lu, G.S. Luo, Intensification of fast exothermic reaction by gas agitation in a microchemical system, AIChE J. 60 (7) (2014) 2724–2730
[40] J.S. Zhang, K. Wang, Y.C. Lu, G.S. Luo, Beckmann rearrangement in a microstructured chemical system for the preparation of ε-caprolactam, AIChE J. 58 (3) (2012) 925–931
[41] A. Nagaki, M. Togai, S. Suga, N. Aoki, K. Mae, J. Yoshida, Control of extremely fast competitive consecutive reactions using micromixing. Selective Friedel-Crafts aminoalkylation, J Am Chem Soc 127 (33) (2005) 11666–11675
[42] S. Suga, A. Nagaki, J.I. Yoshida, Highly selective Friedel-Crafts monoalkylation using micromixing, Chem Commun (Camb) (3) (2003) 354–355
[43] J.J. Heiland, R. Warias, C. Lotter, L. Mauritz, P.J. Fuchs, S. Ohla, K. Zeitler, D. Belder, On-chip integration of organic synthesis and HPLC/MS analysis for monitoring stereoselective transformations at the micro-scale, Lab Chip 17 (1) (2016) 76–81
[44] Z. Fang, W. He, T. Tu, N. Lv, C.H. Qiu, X. Li, N. Zhu, L. Wan, K. Guo, An efficient and green pathway for continuous Friedel-Crafts acylation over α-Fe₂O₃ and CaCO₃ nanoparticles prepared in the microreactors, Chem. Eng. J. 331 (2018) 443–449
[45] G.A. Olah, Friedel-Crafts and related reactions: Acylation and related reactions. Interscience Publishers (1963)
[46] C. Reichardt, T. Welton, Solvents and solvent effects in organic chemistry[M]. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA, 2010
[47] B.S. Furniss, Vogel's textbook of practical organic chemistry. World Scientific (2004)