Citation: Zhang Zishu, Zhao Yulong, Geng Huiling. Chlorosulfonation of Acetanilide in a Dual-Temperature-Zone Silicon Carbide Microchannel Reactor and Synthesis of Sulfasalazine[J]. Chinese Journal of Organic Chemistry, ;2020, 40(8): 2387-2393. doi: 10.6023/cjoc202003053 shu

Chlorosulfonation of Acetanilide in a Dual-Temperature-Zone Silicon Carbide Microchannel Reactor and Synthesis of Sulfasalazine

a.
College of Chemistry＆Pharmacy, Northwest Agriculture and Forestry University, Yangling, Shaanxi 712100
b.
Shandong Jinde New Material Company Ltd., Linshu, Shandong 262700

Corresponding author: Geng Huiling, genghuiling@nwsuaf.edu.cn
Received Date: 23 March 2020
Revised Date: 7 May 2020
Available Online: 8 June 2020
Fund Project: National Training Program of Innovation and Entrepreneurship for Undergraduates 2019-4Project supported by the National Natural Science Foundation of China (No. 31572038) and the National Training Program of Innovation and Entrepreneurship for Undergraduates (No. 2019-4)National Natural Science Foundation of China 31572038

Figures(5)

Chlorosulfonation of acetanilide was accomplished within 10 min in up to 96% yield via a highly thermoconductive and corrosion-resistant dual-temperature-zone silicon carbide microchannel reactor. The yield of pilot production was up to 92%. In the first stage, low reaction temperature (40℃) was employed to effect a high sulfonation selectivity at the para position of acetanilide. In the second stage, a higher reaction temperature (100℃) led to a faster formation of chlorosulfonation product. To illustrate the application of this reaction, sulfasalazine with antimicrobial and anti-inflammatory activities was synthesized in total yield of 75% via chlorosulfonation, sulfamide formation, hydrolysis under base conditions, diazotization and coupling with salicylic acid. The two-step continuous reaction helped to solve the problems in batch reactor, such as low temperature leading to slow reaction and high temperature resulting byproducts and/or temperature runaway, the safety concern aroused by heat accumulation, and the polution caused by the use of large excess of chlorosulfonic acid in batch production. The above research provides technical support for the large-scale industrial production of p-acetylaminobenzenesulfonyl chloride and its sulfonamides.
- acetanilide,
- chlorosulfonation,
- microchannel reactor,
- intrinsic safety
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