Practical Chemoselective Aromatic Substitution: Highly Efficient Dinitrification of N-Phenylbenzenesulfonamide for Synthesis of N-(2,4-dinitrophenyl)benzenesulfonamide

doi:10.6023/cjoc202402008

Chinese Journal of Organic Chemistry ›› 2024, Vol. 44 ›› Issue (9): 2915-2923.DOI: 10.6023/cjoc202402008 Previous Articles Next Articles

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实用的化学选择性芳香取代: N-苯基苯磺酰胺的高效双硝基化合成N-(2,4-二硝基苯基)苯磺酰胺

徐小波^a, 于晓^a, 夏成才^b^,^*(), 冀亚飞^a^,^*()

a 华东理工大学药学院制药过程化学工程研究中心上海 200237
b 山东第一医科大学(山东省医学科学院)药学院济南 250117

收稿日期:2024-02-09 修回日期:2024-04-01 发布日期:2024-04-30
通讯作者: 夏成才, 冀亚飞
基金资助:
泰安市科技发展规划(2019GX015); 山东第一医科大学学术推广计划(2019LJ003)

Practical Chemoselective Aromatic Substitution: Highly Efficient Dinitrification of N-Phenylbenzenesulfonamide for Synthesis of N-(2,4-dinitrophenyl)benzenesulfonamide

Xiaobo Xu^a, Xiao Yu^a, Chengcai Xia^b(), Yafei Ji^a()

a Engineering Research Center of Pharmaceutical Process Chemistry; School of Pharmacy, East China University of Science and Technology, Shanghai 200237
b School of Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117

Received:2024-02-09 Revised:2024-04-01 Published:2024-04-30
Contact: Chengcai Xia, Yafei Ji
Supported by:
Science and Technology Development Plan of Tai'an City(2019GX015); Academic Promotion Program of Shandong First Medical University(2019LJ003)

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Abstract

A novel route for dinitrification of N-phenylbenzenesulfonamide to synthesize N-(2,4-dinitrophenyl)benzenesul- fonamide has been developed. The method features convenient operation and good functional group tolerance. This reaction may go through a nitrogen dioxide radical (NO₂•) intermediate, which is generated by the thermal reaction process of sodium nitrate and ammonium persulfate. In addition, it provides direct approach for the preparation of 2,4-dinitroaniline derivatives which are crucial intermediate for the synthesis of benzimidazoles and quinoxaline derivatives.

Key words: N-phenylbenzenesulfonamide, dinitrification, N-(2,4-dinitrophenyl)benzenesulfonamide

Cite this article

Xiaobo Xu, Xiao Yu, Chengcai Xia, Yafei Ji. Practical Chemoselective Aromatic Substitution: Highly Efficient Dinitrification of N-Phenylbenzenesulfonamide for Synthesis of N-(2,4-dinitrophenyl)benzenesulfonamide[J]. Chinese Journal of Organic Chemistry, 2024, 44(9): 2915-2923.

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Fig. & Tab. 7

Figure 1. Biologically active 2,4-dinitroaniline derivatives

Scheme 1. Synthetic Sstrategies of 2,4-dinitroanilines

Entry	Variation from standard conditions	Yield^b/%
1	None	91
2	No (NH₄)₂S₂O₈	nr
3^c	DTPB instead of (NH₄)₂S₂O₈	nr
4^d	TBPB instead of (NH₄)₂S₂O₈	nr
5	K₂S₂O₈ instead of (NH₄)₂S₂O₈	nr
6	NH₄NO₃instead of NaNO₃	66
7	NaNO₂instead of NaNO₃	31
8	CH₃CN instead of DCE	55
9	THF instead of DCE	nr
10	100 ℃/150 ℃ instead of 130 ℃	36/81
11	2 h/4 h instead of 3 h	57/88
12	Under N₂/O₂	85/42

Table 1. Optimization of the reaction conditionsa

Scheme 2. Substrate scope of N-phenylbenzenesulfonamides Reaction conditions: N-phenylbenzenesulfonamides (0.2 mmol), NaNO3 (0.6 mmol), (NH4)2S2O8 (0.8 mmol), DCE (2 mL), air atmosphere, 130 ℃, 3 h, isolated yield. a Rate of recovery.

Scheme 3. Synthetic applications of N-(2,4-dinitrophenyl)benzenesulfonamide Reaction conditions: Step A: 1 (20 mmol), NaNO3 (60 mmol), (NH4)2S2O8 (80 mmol), and DCE (200 mL), air atmosphere, 130 ℃, 6 h; Step B: 2 (15 mmol), TfOH (45 mmol), and DCE (60 mL), argon atmosphere, 100 ℃, 10 h; Step C: 2 (10 mmol), SnCl2 (100 mmol), i-PrOH (60 mmol) and CH3CN (80 mL), air atmosphere, 100 ℃, 12 h.

Scheme 4. Mechanistic studies and control experiments

Scheme 5. Proposed reaction mechanism

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实用的化学选择性芳香取代: N-苯基苯磺酰胺的高效双硝基化合成N-(2,4-二硝基苯基)苯磺酰胺

Practical Chemoselective Aromatic Substitution: Highly Efficient Dinitrification of N-Phenylbenzenesulfonamide for Synthesis of N-(2,4-dinitrophenyl)benzenesulfonamide

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Fig. & Tab. 7

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