Synthesis and Antitumor Activity of Benzoheterocyclic Aryl Sulfide

doi:10.6023/cjoc202401006

Chinese Journal of Organic Chemistry ›› 2024, Vol. 44 ›› Issue (9): 2854-2861.DOI: 10.6023/cjoc202401006 Previous Articles Next Articles

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含苯并杂环芳基硫醚的合成及其抗肿瘤活性研究

杨媛, 牛丽君, 闫泽宇, 叶姗姗, 张变香^*()

山西大学化学化工学院太原 030006

收稿日期:2024-01-07 修回日期:2024-04-26 发布日期:2024-05-16
通讯作者: 张变香
基金资助:
山西省重点研发计划(202202040201009); 中央引导地方科技发展基金(YDZJSX2021C001)

Synthesis and Antitumor Activity of Benzoheterocyclic Aryl Sulfide

Yuan Yang, Lijun Niu, Zeyu Yan, Shanshan Ye, Bianxiang Zhang()

School of Chemistry and Chemical Engineering, Shanxi University, Taiyuan, 030006

Received:2024-01-07 Revised:2024-04-26 Published:2024-05-16
Contact: Bianxiang Zhang
Supported by:
Key Research and Development Plan of Shanxi Province(202202040201009); Central Government Guides Local Science and Technology Development Fund Projects(YDZJSX2021C001)

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Abstract

Aryl thioethers containing benzene heterocycles were synthesized from reaction of 2-mercaptobenzazoles with cyclic diaryl iodonium salts by CuI catalyst. The target products were characterized by ¹H NMR, ¹³C NMR and UV-Vis spectroscopies. The optimum reaction conditions were discussed, and the highest yield of the target product reached 95%. The optical properties and physiological activities of the products were also tested and analyzed. At the same time, anti-tumor activity tests were conducted on the products, and some products showed good anti-tumor activity. Compared with linear diaryliodonium salts, the iodobenzene by-product generated in the reaction is immobilized in the product, which improves the atom economy, and the C—I bond in the molecular structure provides a reaction site for subsequent reactions or applications.

Key words: 2-mercaptobenzazoles, cyclic diaryl iodonium salts, arylsulfide, benzohybrid ring

Cite this article

Yuan Yang, Lijun Niu, Zeyu Yan, Shanshan Ye, Bianxiang Zhang. Synthesis and Antitumor Activity of Benzoheterocyclic Aryl Sulfide[J]. Chinese Journal of Organic Chemistry, 2024, 44(9): 2854-2861.

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Fig. & Tab. 10

Figure 1. Structures of heterocyclic aromatic sulfides

Scheme 1. Synthesis strategies of C—S bond

Scheme 2. Synthesis route of compound 3

Entry	Base	Temp./℃	Solvent	Catalyst	Time/h	Yield/%
1	K₂CO₃	130	DMF	—	12	34
2	K₂CO₃	130	TCE^b	—	12	23
3	K₂CO₃	130	DMF	CuI	12	76
4	K₂CO₃	130	TCE	CuI	12	37
5	Et₃N	130	DMF	CuI	12	21
6	—	130	DMF	CuI	12	17
7	Et₃N	130	TCE	CuI	12	14
8	K₂CO₃	80	DMF	CuI	12	47
9	K₂CO₃	140	DMF	CuI	12	69
10	K₂CO₃	130	DMF	CuI	6	59
11	K₂CO₃	130	DMF	CuI	24	72

Table 1. Optimization of reaction conditions

Entry	3 (yield)	λ_max/nm	ε/(L•mol^－1•cm^－1)
1		235	8.08×10⁴
2		229	8.15×10⁴
3		231	8.24×10⁴
4		232	7.74×10⁴
5		231	7.86×10⁴
6		229	8.36×10⁴
7		229	7.83×10⁴
8	+	235	8.03×10⁴
8		229	8.15×10⁴

Table 2. Reaction of mercaptoazoles 1 and cyclic diphenyl iodonium salts

Figure 2. UV absorption spectra of products 3a~3i

Scheme 3. Possible reaction mechanism

Figure 3. X-ray single crystal diffraction patterns of 3a and 3f

Figure 4. Effect of products 3a~3i on cell activity

Figure 5. Fluorescence staining images of compound 3i on L-O2 and Hela cells Calcein-AM fluorescent dye labels live cells (green), PI dye labels dead cells (red), scale bar: 50 μm.

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含苯并杂环芳基硫醚的合成及其抗肿瘤活性研究

Synthesis and Antitumor Activity of Benzoheterocyclic Aryl Sulfide

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Fig. & Tab. 10

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