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Synthesis 2022; 54(23): 5261-5272
DOI: 10.1055/s-0042-1751357
paper

Optimization of Methyl Anthranilate Synthesis Process by Response Surface Methodology and Its Reaction Mechanism

Ben Wang
a   College of Environment and Safety Engineering, Qingdao University of Science and Technology, Qingdao, Shandong, SD 532, P. R. of China
,
Yanwei Diao
a   College of Environment and Safety Engineering, Qingdao University of Science and Technology, Qingdao, Shandong, SD 532, P. R. of China
,
Jinqiu Yuan
b   College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, Shandong, SD 532, P. R. of China
,
Fuyue Zhang
b   College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, Shandong, SD 532, P. R. of China
,
Haoyu Zhou
b   College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, Shandong, SD 532, P. R. of China
,
Lei Du∗
c   College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, Shandong, SD 532, P. R. of China
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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 mechanism


Publication History

Received: 22 April 2022

Accepted after revision: 08 July 2022

Article published online:
11 August 2022

© 2022. Thieme. All rights reserved

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