阅读说明：本技术 多取代烯酮亚胺及其合成方法 (Polysubstituted ketene imine and synthetic method thereof ) 是由 李健 黄洁 李峰 崔雷 贾学顺 于 2019-09-18 设计创作，主要内容包括：本发明涉及一种多取代烯酮亚胺及其合成方法,该化合物的结构为：<Image he="185" wi="277" file="DEST_PATH_IMAGE001.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>。本发明4-溴-2,6-二甲基苯基异腈和烯炔酮的插入反应,该反应由钯激活炔基三键从而促进了羰基氧的分子内亲核进攻；然后环化生成一个有活性的共振稳定体在此机制下与异腈发生插入反应,可以合成结构较为复杂的多取代烯酮亚胺。该反应条件温和,反应时间短,操作简便,具有良好的原子经济性。本方法为复杂多取代烯酮亚胺的合成提供了一条新的合成路线,在有机合成中具有潜在的应用价值。(The invention relates to a polysubstituted ketene imine and a synthesis method thereof, wherein the compound has the structure as follows: . The insertion reaction of 4-bromo-2, 6-dimethylphenyliisonitrile and alkenone in the invention activates alkynyl triple bond by palladium to promote intramolecular nucleophilic attack of carbonyl oxygen; then cyclizing to generate an active resonance stabilizer which is subjected to insertion reaction with isonitrile under the mechanism, and synthesizing the multi-substituted ketene imine with a complex structure. The method has the advantages of mild reaction conditions, short reaction time, simple and convenient operation and good atom economy. The method provides a new synthetic route for the synthesis of the complex multi-substituted ketene imine, and has potential application value in organic synthesis.)

1. A polysubstituted ketene imine, characterized in that the structure of the compound is:

wherein R is H, methyl, methoxyl, halogen element or trifluoromethyl.

2. A process for the preparation of a polysubstituted alkenone imine according to claim 1, characterized in that the process has the following steps: dissolving 4-bromo-2,6-dimethylphenyl isonitrile and eneynone in tetrahydrofuran according to a molar ratio of 3:1-2:1, stirring at room temperature until the reaction is finished, removing the solvent, and separating and purifying to obtain the multi-substituted ketene imine; the structural formula of the enynone is as follows:(ii) a The structural formula of the 4-bromo-2,6-dimethylphenyl isonitrile is as follows:。

Technical Field

The invention relates to a polysubstituted ketene imine and a synthesis method thereof.

Background

The polysubstituted ketene imine is a compound with a structure similar to allene, and shows high reaction activity in nucleophilic addition reaction, cycloaddition reaction, free radical reaction, migration rearrangement reaction and other reactions. Therefore, the multi-substituted ketene imine is a very important compound and reaction intermediate in organic synthesis, and has important application in heterocyclic compound synthesis and natural product total synthesis, for example, some multi-substituted ketene imine structures are applied to the total synthesis of a drug molecule (S) -Verapamul.

The polysubstituted ketene imines have important research and application values, and people are also continuously dedicated to researching a simple method for synthesizing the ketene imine framework compound. The following methods for constructing the polysubstituted ketene imines have been reported in the literature in recent years:

chang teaches a novel method for producing N-sulfonyl ketene imines based on the reaction of sulfonyl azides with CuAAC of terminal alkynes. According to the method, in the presence of monovalent copper and alkali, sulfonphthalein azide and terminal alkyne undergo CuAAC reaction to obtain an intermediate, and then the intermediate is further isomerized to obtain polysubstituted ketene imine (Scheme 1). See references: bae, L.; Han, H.; Chang, S. high hly efficiency One-Point Synthesis of N-sulfo-aminodinesby Cu-Catalyzed Three-Component of sulfo Azide, Alkyne, and Amine [ J]. J. Am. Chem. Soc. 2005, 127 : 2038.

Scheme 1

Katagiri et al reported a method for synthesizing β -trifluoromethylenone imine. In the method, under the action of triethylamine, one molecule of HCl is removed from chloro imine to obtain ketene imine, and the author further reacts the obtained ketene imine with electrophilic reagents under the action of alkali to obtain other more stable multi-substituted ketene imine (Scheme 2). See references: katagiri, T.T., Handa, M., Asano, H., Asanuma, T.]. Fluorine Chem. 2009, 130 (8): 714.

Scheme 2

Yang et al reported the palladium-catalyzed reaction of isonitriles with alpha-halophosphoric acid vinegates to ketene imines. The reaction has high atom utilization rate and wide substrate application range, and can obtain polysubstituted ketene imine (Scheme3) with moderate to good yield. See references: yang, Q.; Li, C.; Cheng, M. -X.; Yang, S. -D.Palladium-catalysis Migratory Insertion of Isocynides for Synthesis of C-phospheno keenimines [ J. ]]. ACS Catal. 2016, 6 (7) :4715.

Scheme 3

Qiu et al, using an α, α -disubstituted α -isocyanoacetate and an allyl carbonate under Pd catalysis, obtained a polysubstituted ketene imine, which had regioselectivity and better functional group compatibility (Scheme 4). See references: qiu, G.; Sornay, C.; Savary, D.; Zheng, S.; Qian, W.; Zhu, J.; From isonitrile vitamin a ketotenamine intermediate: Palladium-catalyzed 1, 1-carbocyanamide of allyl carbonate by α -isocyanoacetate [ J. ]]. Tetrahedron2018, 74, 6966.

Scheme 4

In the above methods for selectively constructing the multi-substituted ketene imine, the catalyst is expensive, the reaction time is long, the yield is low, and the like. Therefore, the method for synthesizing the polysubstituted ketene imine derivative has important significance, and has the advantages of easily obtained raw materials, mild reaction conditions and simple operation.

Disclosure of Invention

One of the objects of the present invention is to provide a polysubstituted ketene imine.

The invention also aims to provide a synthetic method of the compound.

To achieve the above object, the reaction equation of the present invention is:

according to the reaction mechanism, the invention adopts the following technical scheme:

according to the reaction mechanism, the invention adopts the following technical scheme:

a polysubstituted ketene imine, characterized in that the structure of the compound is:

wherein R is H, methyl, methoxyl, halogen element or trifluoromethyl.

A method for preparing the multi-substituted ketene imine is characterized by comprising the following steps: dissolving 4-bromo-2, 6-dimethylphenyliisonitrile, eneynone and tetrakis (triphenylphosphine) palladium in tetrahydrofuran according to the molar ratio of 3:1-2:1, stirring at room temperature until the reaction is finished, removing the solvent, and separating and purifying to obtain the multi-substituted ketene imine; the structural formula of the enynone is as follows:(ii) a The structural formula of the 4-bromo-2,6-dimethylphenyl isonitrile is as follows:。

the multi-substituted ketene imine contains furyl, the compound containing furyl is an intermediate for synthesizing furan medicaments, the medicament containing furyl plays an important role in treating microbial infection, ulcer, arrhythmia and the like, and the specific compound containing furyl can also regulate the growth of plants.

The invention provides a method for efficiently synthesizing multi-substituted ketene imine with 5 different functional groups, which has the advantages of mild reaction conditions, short reaction time, simple and convenient operation and good atom economy. The invention has important application in organic synthesis, natural products and drug molecule synthesis, is the skeleton of a plurality of chiral ligands, and is also used for synthesizing nitrile compounds containing quaternary carbon centers.

Drawings

FIG. 1 is a single crystal diagram of Compound 3 a.

FIGS. 2-11 show nuclear magnetic hydrogen and carbon spectra of compounds 3a-3e, respectively.

Detailed Description

The synthesis of the polysubstituted ketene imines according to the present invention is illustrated in detail below with reference to the accompanying drawings, but the present invention is not limited to the following examples. Preferred embodiments of the present invention have been described in detail for the purpose of providing a thorough understanding of the present invention.