磁性纳米负载对甲苯磺酸催化串联合成稠合多环的1,5-苯并氧氮杂䓬类化合物

doi:10.6023/cjoc202304002

摘要/Abstract

1,5-苯并氧氮杂䓬化合物是药物研发过程中发现的一类重要活性物质, 具有抗惊厥、抗肿瘤、改善脑缺血等性质. 开发了一种新颖、高效、绿色的三组分串联反应. 即以取代的邻氨基苯酚、β-环状二酮和活性羰基化合物为原料, 以自制的磁性纳米负载对甲苯磺酸(CoFe₂O₄@SiO₂-PTSA)为催化剂, 无水乙醇为溶剂, 室温条件下一锅法合成了37个未见文献报道、结构多样的稠合1,5-苯并氧氮杂䓬化合物, 并提出了催化串联合成反应机理. 该方法摒弃了传统芳香卤化物强碱脱卤化氢偶联方法, 具有合成方法新颖、反应条件温和、反应过程绿色、高效、时间短、磁性纳米催化剂可回收利用等优势, 为该类化合物的有效合成提供了方法学参考.

关键词: 1,5-苯并氧氮杂䓬, 多组分串联反应, 绿色合成

1,5-Benzoxazepine is an important active substance found in the development of new drugs. It has the properties of anticonvulsant, anti-tumor and improving cerebral ischemia. In this work, novel, efficient and green three-component domino reactions were developed, which used substituted o-aminophenol, β-cyclic diketones and active carbonyl compounds as raw materials, self-made magnetic nano-supported p-toluenesulfonic acid (CoFe₂O₄@SiO₂-PTSA) as catalyst, anhydrous ethanol as solvent, at room temperature. 37 fused 1,5-benzoxazepines with diverse structures were synthesized in one pot, and the mechanism of catalytic domino synthesis was proposed. This method abandons the traditional strong base dehalogenation hydrogen coupling method of aromatic halides, and has the advantages of novel synthesis method, mild reaction conditions, green reaction process, high efficiency, short time, and recyclable magnetic nanocatalyst, which provides a methodological reference for the effective synthesis of such compounds.

Key words: 1,5-benzoxazepine, multicomponent domino reaction, green synthesis

引用此文

李硕, 王明亮, 周来运, 王兰芝. 磁性纳米负载对甲苯磺酸催化串联合成稠合多环的1,5-苯并氧氮杂䓬类化合物[J]. 有机化学, 2023, 43(11): 3977-3988.

Shuo Li, Mingliang Wang, Laiyun Zhou, Lanzhi Wang. Magnetic Nano-Supported p-Toluenesulfonic Acid Catalyzed Synthesis of Fused Polycyclic 1,5-Benzoxazepines via Domino Reactions[J]. Chinese Journal of Organic Chemistry, 2023, 43(11): 3977-3988.

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图/表 8

图1. 1,5-苯并氧氮杂?化合物的医药应用

Figure 1. Pharmaceutical applications of 1,5-benzoxazepines

图式1. 合成方法探究

Scheme 1. Research on synthesis method

Entry	Solvent	Temp./℃	Catalyst^b	Time/h	Yield^d/%
1	EtOH	r.t.^d	—	14.0	—
2	EtOH	r.t.	CeCl₃	12.0	23
3	EtOH	r.t.	CoCl₂	12.0	26
4	EtOH	r.t.	PTA(磷钨酸)	6.5	34
5	EtOH	r.t.	PMA(磷钼酸)	6.5	33
6	EtOH	r.t.	AcOH(乙酸)	6.0	67
7	EtOH	r.t.	PTSA(对甲苯磺酸)	6.0	73
8	EtOH	r.t.	CoFe₂O₄	12.0	25
9	EtOH	r.t.	CoFe₂O₄@SiO₂-PTSA^e	7.0	80
10	EtOH	0	CoFe₂O₄@SiO₂-PTSA	10.0	47
11	EtOH	50	CoFe₂O₄@SiO₂-PTSA	6.0	55
12	EtOH	75	CoFe₂O₄@SiO₂-PTSA	6.0	49
13	MeOH	r.t.	CoFe₂O₄@SiO₂-PTSA	7.0	78
14	PhMe	r.t.	CoFe₂O₄@SiO₂-PTSA	7.0	37
15	MeCN	r.t.	CoFe₂O₄@SiO₂-PTSA	7.0	41
16	DCE	r.t.	CoFe₂O₄@SiO₂-PTSA	7.0	46
17	DCM	r.t.	CoFe₂O₄@SiO₂-PTSA	7.0	42
18	THF	r.t.	CoFe₂O₄@SiO₂-PTSA	7.0	25

表1. 多组分串联反应最优条件的筛选a

Table 1. Selection of optimal conditions for multi-component series reaction

图2. CoFe2O4@SiO2-PTSA的FT-IR (A)、XRD (B)、VSM (C)和BET (D)

Figure 2. FT-IR (A), XRD (B), VSM (C) and BET (D) of CoFe2O4@SiO2-PTSA

图3. CoFe2O4@SiO2-PTSA的SEM (a)、TEM (b)和EDS (c)

Figure 3. SEM (a), TEM (b) and EDS (c) of CoFe2O4@SiO2-PTSA

表2. 苯并氧氮杂?类化合物的底物范围a

Table 2. Substrate range of benzoxazepines compounds

图式2. 1,5-苯并氧氮杂?化合物的反应机理

Scheme 2. Reaction mechanism of 1,5-benzoxazepines

图4. CoFe2O4@SiO2-PTSA的重复使用数

Figure 4. Reusability of CoFe2O4@SiO2-PTSA Reusability of CoFe2O4@SiO2-PTSA

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