阅读说明：本技术 2,5-二芳基-3-氰基吡咯化合物的制备方法 (The preparation method of 2,5- diaryl -3- cyanopyrrole compound ) 是由 章国林 王紫娟 俞永平 于 2019-08-19 设计创作，主要内容包括：本发明公开了一种2,5-二芳基-3-氰基吡咯化合物的制备方法,包括以下步骤：在溶剂中,2-苯乙酰基丙二腈类化合物在醋酸钯的催化下,与取代苯硼酸化合物发生反应,反应温度为95～105℃,反应时间为20～30小时；所得的反应液经后处理,得2,5-二芳基-3-氰基吡咯化合物。本发明使用易得的原料,通过串联反应在环合构建吡咯环的同时,在2,5-位引入了两个芳基,从而得到2,5-二芳基-3-氰基吡咯化合物。(The invention discloses one kind 2; the preparation method of 5- diaryl -3- cyanopyrrole compound; the following steps are included: in a solvent; 2- phenylacetyl group malononitrile derivative is under the catalysis of palladium acetate; it reacts with substituted benzene boronic acid compounds; reaction temperature is 95~105 DEG C, and the reaction time is 20~30 hours；Resulting reaction solution is post-treated, obtains 2,5- diaryl -3- cyanopyrrole compound.The present invention introduces two aryl at 2,5- through tandem reaction while cyclization constructs pyrrole ring using the raw material being easy to get, so that 2 are obtained, 5- diaryl -3- cyanopyrrole compound.)

The preparation method of 1.2,5- diaryl -3- cyanopyrrole compounds, it is characterized in that the following steps are included:

1), in a solvent, the 2- phenylacetyl group malononitrile derivative as shown in formula I is under the catalysis of palladium acetate, with II institute of formula The substituted benzene boronic acid compounds shown react, 2- phenylacetyl group malononitrile derivative, substituted benzene boronic acid compounds, palladium acetate Molar ratio be 1:1.5:0.2, reaction temperature be 95~105 DEG C, the reaction time be 20~30 hours；

In formula, Ar₁For phenyl, 4- aminomethyl phenyl, 4- chlorphenyl, 3- chlorphenyl, 4- methoxyphenyl；Ar₂For phenyl, 4- methyl Phenyl, 4- chlorphenyl, 3- chlorphenyl, 2- chlorphenyl, 4- methoxyphenyl；

2), the resulting reaction solution of step 1) is post-treated, obtains 2,5- diaryl -3- cyanopyrrole compound.

2. the preparation method of 2,5- diaryl -3- cyanopyrrole compound according to claim 1, it is characterized in that:

The post-processing of the step 2) are as follows: by the resulting reaction solution of step 1) after suction filtered through kieselguhr, Rotary Evaporators are spin-dried for removing Remove solvent；Gained concentrate carries out silica gel column chromatography, obtains 2,5- diaryl -3- cyanopyrrole compound.

3. the preparation method of 2,5- diaryl -3- cyanopyrrole compound according to claim 1 or 2, it is characterized in that:

The solvent is toluene.

4. the preparation method of 2,5- diaryl -3- cyanopyrrole compound according to claim 2, it is characterized in that:

The solvent of 12.0~18.0ml of 2- phenylacetyl group malononitrile derivative adapted of every 1mmol.

Technical field

The present invention relates to the preparation method of one kind 2,5- diaryl -3- cyanopyrrole compound, i.e. 2- phenylacetyl group the third two Nitrile compounds react to obtain 2,5- diaryl -3- cyanopyrrole with substituted benzene boronic acid compounds under the catalysis of palladium acetate Compound.

Background technique

Azole derivatives are a kind of important penta azacyclo compounds, and are widely present in natural products and bioactivity In molecule, for example, ferroheme, chlorophyll, bile pigment, certain amino acid, certain alkaloids and some enzymes basic structure list Member.Azole derivatives show multiple biological activities, including antioxidant activity, the inhibitory activity to amine oxidase, antibiotic property, resist Tumour and anti-inflammatory etc. are therefore widely used in numerous aspects such as medicine, pesticide, food, daily-use chemical industry, coating, weaving.

Azoles usually pass through 1,4- dicarbonyl compound and synthesize with the condensation reaction of amine.Due to regioselectivity Difference, pyrroles are easier to the disadvantages of being oxidized, and cause the yield for synthesizing polysubstituted pyrrole usually lower, therefore, develop polysubstituted pyrrole The synthetic method coughed up is particularly important.Document report 2,5- diaryl -3- cyanopyrrole compound synthesis method (Chieh- Kai, ChanYi-Ling, ChanYu-Lin, et al.Journal of Organic Chemistry, 2016,81 (17), 8112-8120): using 2- cyano-Isosorbide-5-Nitrae-cyclohexadione compounds and ammonium acetate as raw material, using methanol as solvent, reflux obtains 2,5- Diaryl -3- cyanopyrrole compound (formula 1).But there are raw material 2- cyano -1,4- cyclohexadione compounds to be not easy to obtain for this reaction The disadvantages of obtaining.

In this method, 2- cyano-Isosorbide-5-Nitrae-cyclohexadione compounds: the molar ratio of ammonium acetate is 1:2.1；Solvent for use is first Alcohol；It is reacted under counterflow condition, reaction time 2h；Yield is 83.08%-87.11%.

Summary of the invention

The technical problem to be solved in the present invention is to provide a kind of raw materials to be easy to get, the 2,5- diaryl -3- cyano pyrrole of high income Cough up the preparation method of compound.

In order to solve the above technical problem, the present invention provides the preparations of one kind 2,5- diaryl -3- cyanopyrrole compound Method, comprising the following steps:

1), in a solvent, the 2- phenylacetyl group malononitrile derivative as shown in formula I is under the catalysis of palladium acetate, with formula Substituted benzene boronic acid compounds shown in II react, 2- phenylacetyl group malononitrile derivative, substituted benzene boronic acid compounds, vinegar The molar ratio of sour palladium is 1:1.5:0.2, and reaction temperature is 95~105 DEG C (preferably 100 DEG C), and the reaction time is 20~30 hours (preferably 24 hours)；

In formula, Ar₁For phenyl, 4- aminomethyl phenyl, 4- chlorphenyl, 3- chlorphenyl, 4- methoxyphenyl；Ar₂For phenyl, 4- Aminomethyl phenyl, 4- chlorphenyl, 3- chlorphenyl, 2- chlorphenyl, 4- methoxyphenyl；

2), the resulting reaction solution of step 1) is post-treated, obtains 2,5- diaryl -3- cyanopyrrole compound.

The improvement of preparation method as 2,5- diaryl -3- cyanopyrrole compound of the invention: the step 2) Post-processing are as follows: by the resulting reaction solution of step 1) after suction filtered through kieselguhr, Rotary Evaporators are spin-dried for removing solvent；Gained concentrate Silica gel column chromatography is carried out, 2,5- diaryl -3- cyanopyrrole compound is obtained.

The further improvement of preparation method as 2,5- diaryl -3- cyanopyrrole compound of the invention: described molten Agent is toluene.

The further improvement of preparation method as 2,5- diaryl -3- cyanopyrrole compound of the invention: every 1mmol 2- phenylacetyl group 12.0~18.0ml of malononitrile derivative adapted (for example, 15.0ml) solvent.

The present invention is with Pd (OAc)₂For catalyst, 2,5- diaryl -3- cyanopyrrole chemical combination has been synthesized by tandem reaction Object, as shown in Equation 2.

2,5- diaryl -3- cyanopyrrole compound synthesis method provided by the invention has the following characteristics that

(1) this method is easy to operate, and yield is higher；

(2) raw material of the present invention is simple and easy to get, and synthetic method is novel, has no document report.

In conclusion the present invention is using the raw material that is easy to get, through tandem reaction while cyclization constructs pyrrole ring, 2, 5- introduce two aryl and obtain 2,5- diaryl -3- cyanopyrrole compound, and literature method raw material can be overcome to be not easy to obtain The disadvantages of obtaining, this method is there is not yet pertinent literature is reported.

Specific embodiment

It below will the present invention is further illustrated by embodiment.Wherein m2 and m3 is known compound.