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DOI: 10.1055/s-0042-1751357
Optimization of Methyl Anthranilate Synthesis Process by Response Surface Methodology and Its Reaction Mechanism
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Abstract
In this paper, a unique process for the production of methyl anthranilate (MA) was investigated. The factors of the phthalimide/sodium hypochlorite/methanol molar ratio, reaction temperature, hydrolysis temperature, and water consumption on the yield and purity of MA were analyzed. Response surface methodology (RSM) was used to optimize conditions for the semi-batch synthesis process of MA. The best synthetic conditions for the formation of MA were reaction temperature 0.5 °C, hydrolysis temperature 70 °C and n(phthalimide)/n(sodium hypochlorite)/n(methanol) = 1:2.03:5.87, and water consumption m(H2O)/m(phthalimide) = 7.16:1. The yield of MA could reach 90% under the optimal conditions, which is more than 10% higher than that of the previous semi-batch process. Furthermore, the reaction mechanism was investigated by infrared spectroscopy analysis, and the mechanism of ester group formation and the structure of intermediate products are proposed. The byproduct of the reaction was studied by GC-MS analysis, a byproduct called 2-cyanobenzoic acid has been discovered. Therefore, an unprecedented reaction mechanism of the whole synthesis process is proposed.
Key words
methyl anthranilate - Hofmann reaction - response surface methodology - reaction mechanismPublikationsverlauf
Eingereicht: 22. April 2022
Angenommen nach Revision: 08. Juli 2022
Artikel online veröffentlicht:
11. August 2022
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References
- 1 Tonne P, Hagen J. US 4,464,537, 1984
- 2 Sommer S, Fraatz MA, Büttner J, Salem AA, Rühl M, Zorn H. J. Agric. Food Chem. 2021; 69: 14222
- 3 Li T, Sun X, Chen H, He B, Mei Y, Wang D, Li J. Food Microbiol. 2020; 86: 103356
- 4 Bernklau E, Hibbard B, Norton A, Bjostad L. J. Econ. Entomol. 2016; 109: 1683
- 5 Chambers AH, Evans SA, Folta KM. J. Agric. Food Chem. 2013; 61: 12625
- 6 Rodrigues N. dN, Cebrián J, Montané A, Mendez S. AppliedChem 2021; 1: 50
- 7 Yadav G, Krishnan M. Org. Process Res. Dev. 1998; 2: 86
- 8 Li M, Pu S, Zhang W. Guangdong Chem. Ind. 2007; 34: 70
- 9 Zhu XH. Contemp. Chem. Ind. 2012; 41: 913
- 10 Hofmann AW. Ber. Deutsch. Chem. Ges. 1881; 14: 2725
- 11 Kilpper G, Grimmer J, Tonne P, Horn HC, Hetzel E. US 4,328,339, 1982
- 12 Li F, Huang C.-H, Xie L.-N, Qu N, Shao J, Shao B, Zhu B.-Z. Sci. Rep. 2016; 6: 39207 org/10.1038/srep39207
- 13 Heyman DA. J. Heterocycl. Chem. 1978; 15: 1131
- 14 Mohammed IY, Abakr YA, Yusup S, Kazi FK. J. Cleaner Prod. 2017; 142: 1848
- 15 Ranic M, Nikolic M, Pavlovic M, Buntic A, Siler-Marinkovic S, Dimitrijevic-Brankovic S. J. Cleaner Prod. 2014; 80: 69
- 16 Ghafarzadeh M, Abedini R, Rajabi R. J. Cleaner Prod. 2017; 150: 361
- 17 Wu Y, Yi L, Li E, Li Y, Lu Y, Wang P, Zhou H, Liu J, Hu Y, Wang D. Int. J. Biol. Macromol. 2017; 102: 68
- 18 Ferreira SL, Bruns RE, Ferreira HS, Matos GD, David JM, Brandao GC, da Silva EG, Portugal LA, dos Reis PS, Souza AS, dos Santos WN. Anal. Chim. Acta 2007; 597: 179
- 19 Nhan NP. T, Hien TT, Nhan LT. H, Anh PN. Q, Huy LT, Nguyen TC. T, Nguyen DT, Bach LG. Solid State Phenom. 2018; 279: 235
- 20 Wang T, Zhou Y, Cao S, Lu J, Zhou Y. Ecotoxicol. Environ. Saf. 2019; 172: 334
- 21 Huang J, Huang D, Wang F, Xu J. CIESC J. 2020; 72: 158
- 22 Gu JY. Sci. Technol. Eng. 2003; 5: 462
- 23 Liu Y, Zhao H, Li G. Isocyanate, 1st ed. Academic Press/Chemical Industry Press,; ISBN: 7-5025-5122-0, 2004: 39-40
- 24 Ferstandig L, Scherrer RA. J. Am. Chem. Soc. 1959; 81: 4838
- 25 Wolf ME, Vandezande JE, Schaefer HF. Phys. Chem. Chem. Phys. 2021; 23: 18535
- 26 Shi F, Ren M, Li R. Anhui Chem. Ind. 2018; 5: 70
- 27 Wang WL. Inorg. Chem. Ind. 2007; 39: 12
- 28 Zhong K, Wang Q. Carbohydr. Polym. 2010; 80: 19
- 29 Elfghi FM. Chem. Eng. Res. Des. 2016; 113: 264
- 30 Yuan Y, Zhang Y, Liu T, Hu P, Zheng Q. J. Cleaner Prod. 2019; 234: 494
- 31 Morero B, Groppelli ES, Campanella EA. J. Cleaner Prod. 2017; 141: 978
- 32 Alipanahpour Dil E, Ghaedi M, Ghezelbash GR, Asfaram A, Purkait MK. J. Ind. Eng. Chem. 2017; 48: 162
- 33 Zhang H.-Z, Fang S.-P, Liu Z.-W, Zhang X.-Q. J. Mater. Cycles Waste Manage. 2021; 23: 976
- 34 Zou Y, Zhang T, Wang G, Zhou M, Xiong Y, Huang S, Li H, Liu X. J. Ind. Eng. Chem. 2020; 82: 113
- 35 Huang J, Geng Y, Wang Y, Xu J. Ind. Eng. Chem. Res. 2019; 58: 16389
- 36 He P, Wen X, Li W. Chem. Res. 2017; 28: 421