电化学条件下由二苄胺合成N-亚苄基苄胺及衍生化研究

doi:10.6023/A24040119

摘要/Abstract

N-亚苄基苄胺及其衍生物是化学和制药工业中的重要功能分子, 已被广泛应用在药物化学、材料科学和天然产物合成等, 如合成抗癌和抗炎剂. 本工作发展了一种电化学条件下, 以碳棒(＋)和铂片(－)作为电极、乙酸乙酯为溶剂、四丁基高氯酸铵(n-Bu₄NClO₄)为电解质, 室温下由二苄胺合成N-亚苄基苄胺的方法, GC产率高达96%, 并利用“一锅法”串联反应对其进行衍生化, 制备得到结构更为复杂的N-苄基苄胺类化合物. 该方法条件温和、具有较好的底物普适性、无需氧化还原剂、对空气和水分不敏感、后处理简单等特点, 为制备结构复杂的N-亚苄基苄胺衍生物提供了一种高效、简便且经济的合成策略.

关键词: 二苄胺, N-亚苄基苄胺, 一锅串联反应, 有机电化学合成

N-benzylidene benzylamine and its derivatives are common functional molecules in organic intermediates, fine chemicals and pharmaceuticals, and have been widely used in medicinal chemistry, materials science and natural product synthesis, such as the synthesis of anticancer and anti-inflammatory agents. Electrochemistry has become a powerful tool in organic synthesis to avoid the use of expensive and toxic oxidants or reductants to reduce the production of harmful and toxic by-products. Therefore, In this paper, we report a method for the synthesis of N-benzylidene benzylamine from dibenzylamine under electrochemical conditions, and its derivatization is studied by a one-pot tandem reaction. N-benzylidene benzylamines were electrolyzed at room temperature with graphite rod (Φ=6 mm) and Pt plate (10 mm×10 mm×0.2 mm) as electrode, ethyl acetate as solvent, and tetrabutylammonium perchlorate (n-Bu₄NClO₄) as electrolyte. Sixteen N-benzylidene benzylamines compounds were successfully prepared by this method, and the GC yield was as high as 96%. The “one-pot method” tandem reaction is a simple, fast and environment-friendly synthesis and preparation method, which uses simple, easy-to-obtain and inexpensive raw materials to prepare complex structures and high-value organic compounds through this “one-pot method” series reaction, without the separation and purification of intermediate products to obtain the required products, especially suitable for reaction systems with unstable intermediate products, which has the advantages of simple operation, simple post-treatment, less product loss, and less waste. In order to highlight the application value of N-benzylidene benzylamines, the derivatization reaction of N-benzylidene benzylamine by one-pot tandem method was further explored. And 15 derivatization products were prepared, isolated yield up to 86%. Finally, through control experiments, salt bridge experiments, cyclic voltammetry experiments and related literature reports, we speculated the possible reaction mechanism of this reaction. The reaction has the characteristics of mild conditions, wide range of substrates, good tolerance of functional groups, without redox agents and insensitivity to air and moisture. This study provides an efficient and economical synthesis strategy for the preparation of N-benzylidene benzylamines derivatives.

Key words: dibenzylamine, N-benzylidene benzylamine, one-pot tandem reaction, organic electrosynthesis

引用此文

热孜古丽•玉努斯, 卡迪尔亚•阿布都外力, 罗时玮, 阿布都热西提•阿布力克木. 电化学条件下由二苄胺合成N-亚苄基苄胺及衍生化研究[J]. 化学学报, 2024, 82(8): 843-848.

Yunusi Reziguli, Abuduwaili Kadierya, Shiwei Luo, Abudu Rexit Abulikemu. Synthesis of N-Benzylidene Benzylamine from Dibenzylamine and Derivatization under Electrochemical Conditions[J]. Acta Chimica Sinica, 2024, 82(8): 843-848.

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图/表 8

图1. 苄基胺氧化转化为N-亚苄基苄胺

Figure 1. Oxidation of benzylamine to N-benzylidene benzylamine

Entry	Various of standard conditions	2a Yield^b/%
1	None	96%
2	CH₃CH₂OH as solvent	92%
3	CH₃CN as solvent	92%
4	DCE as solvent	81%
5	THF as solvent	82%
6	DMF as solvent	80%
7	TBAB instead of n-Bu₄NClO₄	92%
8	n-Bu₄NPF₆ instead of n-Bu₄NClO₄	77%
9	TBAF instead of n-Bu₄NClO₄	77%
10	TBAI instead of n-Bu₄NClO₄	32%
11	n-Bu₄NHSO₄ instead of n-Bu₄NClO₄	15%
12	n-Bu₄NBF₄ instead of n-Bu₄NClO₄	trace
13	C(＋)/C(－)	83%
14	Pt(＋)/Pt(－)	74%
15	Pt(＋)/C(－)	61%
16	8 mA instead of 10 mA	91%
17	12 mA instead of 10 mA	91%
18	n-Bu₄NClO₄ (0.02 mol/L)	90%
19	n-Bu₄NClO₄ (0.1 mol/L)	95%
20	without electrolyte (24 h)	trace

表1. 合成N-亚苄基苄胺的反应条件筛选a

Table 1. Optimization of reaction conditions for the synthesis of N-benzylidene benzylamine

表2. N-亚苄基苄胺合成底物扩展a,b

Table 2. Substrates scope for the synthesis of N-benzylidene benzylamine

Entry	Various of standard conditions	4a Yield^b/%
1	None	86%
2	1,4-DCB (1.2 equiv.)	51%
3	1,4-DCB (1.3 equiv.)	72%
4	1,4-DCB (1.6 equiv.)	79%
5	Et₃N (3.0 equiv.)	61%
6	Et₃N (1.0 equiv.)	69%
7	no Et₃N (24 h)	53%

表3. N-亚苄基苄胺的衍生化反应条件优化a

Table 3. Optimization of reaction conditions for derivatization of N-benzylidene benzylamine

表4. N-亚苄基苄胺的衍生化反应底物扩展a,b

Table 4. Substrates expansion for derivatization reaction of N-benzylidene benzylamine

图2. 控制实验

Figure 2. Control experiments

图3. 循环伏安法实验. 条件: 0.1 mol/L n-Bu4NPF6溶解于乙腈中. 以石墨碳为工作电极, Ag/AgCl (3 mol/L KCl)为参比电极, 铂片为对电极, 扫速为100 mV/s. (a) 1a (1 mmol/L); (b) 2a (1 mmol/L); (c) 3 (1 mmol/L)

Figure 3. Cyclic voltammograms. Conditions: a graphite rod working electrode, Ag/AgCl (3 mol/L KCl) reference electrode, and a platinum counter electrode, n-Bu4NPF6 (0.1 mol/L in MeCN), 100 mV/s scan rate. (a) 1a (1 mmol/L); (b) 2a (1 mmol/L); (c) 3 (1 mmol/L)

图4. 可能的反应机理

Figure 4. Proposed reaction mechanism

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