Preparation method of bisindolyl phenylethane compounds

Abstract

The invention belongs to the technical field of synthesis of organic compounds, and particularly relates to a preparation method of bisindolyl phenylethane compounds. According to the preparation method of the bisindolyl phenylethane compounds, the acetophenone compound and the indole compound are used as raw materials, dihalogen hydantoin is used as a catalyst for catalytic reaction, the problem that the acetophenone compound is large in steric hindrance and difficult to react, and consequently the product yield is low is effectively solved, and under the mild reaction condition, high-efficiency and high-yield preparation of the bisindolyl phenylethane compound is realized; and moreover, the components of the whole reaction system are relatively simple, so that the post-treatment step is facilitated.

Description

technical field [0001] The invention belongs to the technical field of organic compound synthesis, and in particular relates to a preparation method of bisindole phenylethane compounds. Background technique [0002] Indole compounds are a large class of compounds with benzo five-membered nitrogen heterocyclic structural units, which widely exist in nature. Indole compounds are an important class of heterocyclic derivative alkaloids, which show a variety of biological activities in vivo. At present, a large number of drugs containing indole structures have been listed on the market, which has played a very important role in the treatment of human diseases; at the same time, indole compounds have been widely used in medicines, pesticides, spices, dyes, and intermediates of other fine chemical products. field. [0003] Bisindole derivatives are an important class of indole compounds, and their structural units are fully reflected in many natural products and drugs. In recent...

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Problems solved by technology

For example, Liu Liangxian et al reported the synthesis of 3,3'-(benzylidene)bisindole by using a protonic acid catalyst such as p-toluenesulfonic acid to catalyze the reaction of benzaldehyde and indole at room temperature. After 0.5h of reaction, 90 % yield (Chen Zhengwang, Liu Liangxian, Chemical Bulletin, 2014,77,922-924); Another example, Xia Chengcai etc. have developed a kind of catalyzed by strongly acidic ion exchange resin that benzaldehyde and indole are converted into bis-indolylmethanes An effective synthesis method of derivatives, which uses water as a solvent, realizes that the catalyst can be recycled for 6 times, and obtains various bis-indolylmethane compounds with higher yields (Zhang Ruize, Wang Guodong, Li Hongshuang, Duan Guiyun, Wang Kai, Xia Chengcai, Organic Chemistry, 2019, 39, 1429-1435); another example, Wangs research group found that Ln(OTf) 3 Such Lewis acid catalysts can catalyze the reaction of indole with aldehydes or ketones in the aqueous phase, and produce bis-indolylmethane-type compounds in high yields. However, when ketones are used as raw materials for the reaction, there is a problem that the reaction is obviously slow , the product yield is also low (D.P.Chen, L.B.Yu,; P.G.Wang, Tetrahydron Letts., 1996,37,4467); even for the bis-indolation of acetophenone, it does not react at all (Xing Ye, Jie Zhengfeng, Liu Fangming, Applied Chemistry, 2009, 26(3), 352-354); Another example, Tang Min used tribromopyridine in his master's thesis to catalyze the synthesis of bisindole alkane compounds in aqueous phase, wherein, for aldehydes For the reaction raw material system, after 2 hours of reaction, the yield of most compounds can be greater than 80%; however, there is a problem of low reactivity for the aromatic ketone reaction principle system, such as when reacting with acetophenone and indole, The reaction was very slow, and after about 72 hours, the yield of the product was only 32% (Tang Min, master's thesis of Jiangxi Normal University, 2009); Shao's research group used potassium hydrogen sulfate as a catalyst to catalyze acetophenone and The bis-indole reaction of indole, the yield of its product 5-nitrobis-indole phenylethane is also only 42% (L.Wang, W.Wei, Y.Guo, J.Xu, S.Shao, Spectrochimica Acta Part A,2011,78,726–731); Adivireddy et al prepared bisindole-p-nitrophenylethane, bisindole-p-methylphenylethane and bisindole in acetonitrile using organic strong acid benzenesulfonic acid as a catalyst M-methylphenylethane, the yield is about 70%, only when the auxiliary frequency is 35kHz ultrasonic intervention, the yield of the three products can reach 88-90% (P.R.Simha, M.S.Mangali, D.K.Gari, P. .Venkatapuram, P.Adivireddy, Journal of Heterocyclic Chemistry, 2017, 54(5), 2717-2724), however, the intervention of ultrasonic instruments greatly limits its application in industrial production

[0005] In summary, the preparation of bisindole compounds in the prior art mostly focuses on the bisindolation of benzaldehyde and indole to realize the synthesis of bisindolylmethane derivatives. However, for bisindoleethane compounds, However, there are few reports on related synthesis processes, and the application is more difficult.

Especially when using acetophenone compounds as raw materials to carry out the bis-indole reaction, due to the existence of methyl groups in the acetophenone structure, its steric hindrance is significantly increased, resulting in low reaction efficiency, or even no reaction (Khaligh, N.G.; Mihankhah, T.; Johan, M.R.; Ching, J.J.J. Mol. Liq. 2018, 259, 260–273; Kalla, R.M.N.; Hong, S.C.; Kim, I. ACS Omega. 2018, 3, 2242-2253)

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