CN-116332979-B - 3-Indole-o-carborane methanol derivative and green synthesis method thereof

Abstract

The invention discloses a 3-indole-o-carborane methanol derivative and a green synthesis method thereof, which comprise the steps of taking 1-aldehyde-o-carborane as a raw material, adding no catalyst or solvent, and synthesizing the 3-indole-o-carborane methanol derivative efficiently through nucleophilic addition reaction of C 3 -H of indole on aldehyde groups in an air atmosphere. The method has the advantages of simple operation, high yield, wide substrate application range and the like. The preparation method of the 3-indole-o-carborane methanol derivative is simple to operate, only needs to add 1-aldehyde-o-carborane and indole into a container, does not need to add a solvent and a metal catalyst in the reaction process, has high reaction yield, does not generate extra waste in the reaction process, and is environment-friendly. The invention provides a green, economical and efficient method for the selective functionalization of o-carborane, lays a technical foundation for further designing the synthesis of o-carborane-heterocyclic derivatives, and provides a new thought for the synthesis of monoindole methanol compounds.

Inventors

• CAO KE
• ZHANG LINGEN
• ZHANG CAIYAN
• Zou Menjin
• YANG KESHENG
• YE YULU
• SUN XIAOYU

Assignees

• 西南科技大学

Dates

Publication Date

20260505

Application Date

20230404

Claims (3)

1. 1. A green synthesis method of a 3-indole-o-carborane methanol derivative, which is characterized by comprising the following steps: To be used for And Is prepared from the raw materials through the steps of C 3 -H pair of (C) The nucleophilic addition reaction of the aldehyde group of the formula (I) efficiently synthesizes the 3-indole-o-carborane methanol derivative, wherein the structural general formula of the 3-indole-o-carborane methanol derivative is as follows: ; Wherein R 1 is any one of alkyl, alkoxy and halogen, R 2 is any one of methyl, n-butyl, benzyl, phenyl and hydrogen, R 3 is any one of methyl, phenyl and substituted phenyl; The said The preparation method of the (C) comprises the following steps: step one, adding into a dry reaction vessel Under the protection of argon, adding dry diethyl ether as a solvent, then placing the reaction system at-78 ℃, slowly dropwise adding n-butyllithium by using a dry injector, reacting the system at-78 ℃ for 1h, adding methyl formate, continuously reacting at-78 ℃ for 2 hours, and monitoring the reaction progress by using a TLC plate; Step two, after the reaction is finished and the system is warmed to room temperature, hydrochloric acid is added for quenching reaction, then ethyl acetate is used for extraction reaction, an organic phase is respectively washed three times by saturated NaHCO 3 solution and saturated NaCl aqueous solution, and the organic phase is collected and dried by anhydrous sodium sulfate; Removing the organic solvent by reduced pressure distillation, and separating by column chromatography with petroleum ether and ethyl acetate as eluent to obtain white solid as 。
2. 2. The green synthesis method of the 3-indole-o-carborane methanol derivative according to claim 1, wherein the certain temperature is 25-60 ℃.
3. 3. A green synthesis method of 3-indole-o-carborane methanol derivative according to claim 1, wherein the following is adopted Wherein R 3 is any one of methyl, phenyl and substituted phenyl.

Description

3-Indole-o-carborane methanol derivative and green synthesis method thereof Technical Field The invention belongs to the technical field of organic synthesis chemical synthesis, and relates to a 3-indole-o-carborane methanol derivative and a green synthesis method thereof. Background The o-carborane is a cluster compound which consists of three elements of carbon, boron and hydrogen and has a regular icosahedron structure, the substituent effect of the o-carborane can be transferred through a three-dimensional cage-shaped surface, electrophilic substitution reaction is easy to occur, and the o-carborane has certain similarity with benzene rings with two-dimensional aromaticity. Since the discovery in the 60 s of the 20 th century, o-carborane and its derivatives have been receiving more and more attention due to their unique photoelectric and biochemical properties, and have shown great application prospects in the fields of rubber industry, nonlinear optics, supermolecular chemistry, coordination chemistry, pharmaceutical chemistry, and the like. Thus, research into the synthetic methodology of o-carborane derivatives is of great importance in promoting the development of carborane chemistry and related material disciplines. As heterocyclic compounds most widely distributed in nature, indole and its derivatives are widely used in the fields of medicines, pesticides, functional materials, and the like. Due to its structural specificity and diversity, it also provides a sense of dexterity for the development of modern synthetic methods, including the construction of the indole skeleton and the functionalization of the indole ring. Research results show that the introduction of different modification groups into indole structures is expected to further improve the biological activity of the compounds and find several potential properties and uses. Indole can undergo nucleophilic addition reaction with aromatic aldehyde under the catalysis of Lewis acid, so as to synthesize indole modified aromatic alcohol skeleton. However, for aromatic aldehydes, most of the reaction products are bisindolomethane compounds, the selective single addition reaction of indole and aromatic aldehyde needs to be carried out under the condition of strong alkali, while o-carborane molecules are resistant to acid and alkali and are easy to remove boron and even degrade under the condition of alkali, so that the selective single addition reaction of o-carborane and indole is a challenging problem, and 3-indole-o-carborane methanol derivatives cannot be obtained in the prior researches. Disclosure of Invention Based on the research foundation of the prior art in the aspect of the selective functionalization of o-carborane and the important application prospect of o-carborane derivatives in the fields of medicine, materials and the like, the invention aims to provide the preparation method of the 3-indole-o-carborane methanol derivatives, which is simple to operate, mild in synthesis condition, wide in application range, green and efficient. Based on the research basis in the selective functionalization of o-carborane, the present invention envisages that 1-aldehyde-o-carborane with three-dimensional aromaticity may undergo nucleophilic addition reactions with the 3-C-H bond of indole. Meanwhile, by utilizing the steric hindrance effect and the electronic effect of the 1-aldehyde-o-carborane, the selective single nucleophilic addition reaction of the 1-aldehyde-o-carborane and the 3-site C-H bond of indole is hopeful to be realized, so that the 3-indole-o-carborane methanol derivative which cannot be obtained in the prior research is obtained. According to the invention, the steric effect and the electronic effect of the 1-aldehyde-o-carborane are utilized, and the selective single addition reaction of the 1-aldehyde-o-carborane and an indole 3-site C-H bond is realized under the condition of no solvent and no catalyst, so that the 3-indole-o-carborane methanol derivative which cannot be obtained in the previous research is obtained. It is an object of the present invention to address at least the above problems and/or disadvantages and to provide at least the advantages described below. To achieve these objects and other advantages and in accordance with the purpose of the invention, there is provided a 3-indole-o-carborane methanol derivative having the general structural formula: Wherein R 1 is any one of alkyl, alkoxy and halogen, R 2 is any one of methyl, n-butyl, benzyl, phenyl and hydrogen, and R 3 is any one of methyl, phenyl and substituted phenyl. The invention also provides a green synthesis method of the 3-indole-o-carborane methanol derivative, which comprises the following steps: To be used for Is prepared from the raw materials through the steps ofC 3 -H pair of (C)The nucleophilic addition reaction of the aldehyde group of the formula (I) efficiently synthesizes the 3-indole-o-carborane methanol derivative, wherein R 1 is