阅读说明：本技术 一种制备n-芳基吡咯化合物的方法 (Method for preparing N-aryl pyrrole compound ) 是由 黄耀兵 罗雨佳 姜飞燕 于 2020-06-04 设计创作，主要内容包括：本发明涉及一种制备N-芳基吡咯化合物的方法。将含有不同取代基的呋喃,不同取代基的芳香胺和固体路易斯酸催化剂混合置于密闭反应器中,在一定催化条件下,制得具有不同取代基的N-芳基吡咯化合物。催化反应条件的反应温度140-210 <Sup>o</Sup>C。所述固体路易斯酸催化剂采用溶胶-凝胶法制备获得,其中以Hf为核心金属元素,介孔分子筛SBA-15为载体。该方法中催化剂制备简单、成本低,反应活性高,耐水性和结构稳定性好,催化反应产率高；同时,该类路易斯酸型催化剂不产生酸质子,避免高温下催化剂对设备腐蚀,反应后处理方便,催化剂可再生,对环境友好。(The present invention relates to a process for the preparation of N-arylpyrrole compounds. Furan containing different substituents, aromatic amine containing different substituents and a solid Lewis acid catalyst are mixed and placed in a closed reactor, and N-aryl pyrrole compounds with different substituents are prepared under certain catalytic conditions. Reaction temperature of catalytic reaction conditions 140- o C. The solid Lewis acid catalyst is prepared by adopting a sol-gel method, wherein Hf is used as a core metal element, and a mesoporous molecular sieve SBA-15 is used as a carrier. The catalyst in the method has the advantages of simple preparation, low cost, high reaction activity, good water resistance and structural stability and high catalytic reaction yield; meanwhile, the Lewis acid type catalyst does not generate acid protonsThe catalyst is free from corroding equipment at high temperature, the treatment after reaction is convenient, and the catalyst is renewable and environment-friendly.)

1. The method for preparing the N-aryl pyrrole compound is characterized in that the N-aryl pyrrole compound is shown as a general formula C, furan compound shown as a general formula A and aromatic amine shown as a general formula B are used as raw materials, and the raw materials react under the catalysis of a solid Lewis acid catalyst to generate the N-aryl pyrrole compound;

。

2. the method of claim 1, wherein:

R¹，R²，R³，R⁴each independently selected from one of hydrogen, aryl, alkoxy having 1 to 3 carbon atoms, alkyl having 1 to 3 carbon atoms and haloalkyl having 1 to 3 carbon atoms.

3. The method of claim 1, wherein:

R⁵，R⁶，R⁷，R⁸，R⁹each independently selected from one of hydrogen, alkyl, alkoxy, nitro, cyano, carboxyl and halogen.

4. The method of claim 1, wherein the solid lewis catalyst is Hf/SBA-15 catalyst comprising hafnium metal supported on a mesoporous molecular sieve SBA-15 support.

5. The method of claim 4, wherein the molar ratio of the Si and Hf elements in the catalyst is 15:1 to 30: 1.

6. The method of claim 5, wherein the molar ratio of the Si and Hf elements in the catalyst is 20: 1.

7. The method of claim 1, wherein: the reaction condition is the reaction temperature of 140-^oAnd C, the reaction time is not less than 6 hours.

8. The method of claim 1, wherein: the molar ratio of the aromatic amine to the furan compound is 1: 3-1: 500.

9. The method of claim 1, wherein: the solid Lewis acid catalyst is prepared by adopting the following sol-gel method:

weighing a certain mass of polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer P123 in hydrochloric acid, and stirring for a certain time; weighing a certain mass of tetraethyl orthosilicate and a certain mass of hafnium tetrachloride, respectively serving as a silicon source and a hafnium source, adding the tetraethyl orthosilicate and the hafnium tetrachloride into the solution, and continuously stirring for a certain time to obtain a suspension; transferring the obtained suspension into a reaction kettle, and standing at the temperature of 100 ℃ for 24 hours; taking out the reaction kettle, cooling to room temperature, filtering, and washing and filtering with deionized water for three times; and drying the washed filter product in an oven overnight to obtain a catalyst precursor, and calcining the catalyst precursor at the temperature of 450-900 ℃ to obtain the Hf/SBA-15 catalyst.

Technical Field

The invention relates to synthesis of an N-aryl pyrrole compound, in particular to a method for preparing the N-aryl pyrrole compound.

Background

Pyrrole is one of the most important heterocyclic compounds in organic chemistry and material science. Pyrrole structural fragments are present in many biologically and pharmaceutically active compounds. Among them, the N-aryl substituted pyrrole compounds exhibit unique biological activities including antibacterial, antiviral, anti-inflammatory and antitumor properties. Therefore, the construction of N-arylpyrrole compounds is a key problem in the field of organic synthesis and pharmaceutical synthesis.

Currently, the main routes for constructing N-arylpyrroles include aza-Wittig reactions [ J. org. chem.1994,59,4551 ], Hantzsch reactions [ Tetrahedron 2001, 57, 1961 ], Paal-Knorr reactions [ J. mol. Cat. A: chem., 2012, 363-. Patent document CN103288701A discloses a 1, 5-diaryl pyrrole derivative which is obtained by using a 1, -4-dicarbonyl compound and an aromatic amine under the catalytic action of a protonic acid, and the yield of most examples is about 40-60%. Patent document US8642640B2 discloses an N-phenylpyrrole compound, also prepared using a 1, 4-dicarbonyl compound and an aromatic amine. In summary, the substrates used in these reactions are usually substituted ketones, aldehydes or amines, which are mostly derived from petrochemical resources, and the yield of the reaction is low. On the background of global resource scarcity and green development, it is more important to explore resources based on renewable resources to construct pyrrole derivatives. On the other hand, the reaction system has very strict requirements on the water content in the reaction raw materials and the solvent, the reaction yield can be greatly reduced due to the extremely small water content, the side reactions are increased, and the requirements on industrial production are not facilitated.

Early studies found that amines were added to furan and that pyrrole products could be detected in the presence of alumina [ j. gen. chem. (USSR) 1937, 7,2945 ] or titania catalyst [ Tetrahedron lett. 1990, 31, 2991 ], but with lower reaction efficiency. Recently, it has been reported that the use of a solid acid H-type zeolite Y catalyst allows the preparation of pyrrole by condensation of aniline with furan under mild conditions [ ACS cat No. 2017, 7, 959 ]. Studies have demonstrated that bronsted acid sites (protonic acids) are the key catalytic sites for the catalyst and that the reaction proceeds through the classical Paal-Knorr reaction pathway. In addition, catalytic reactions of arylamines and furans have been rarely reported. It is known that the protonic acid catalyst has its own limitations in the application process, such as easy deactivation, poor water resistance and easy corrosion to the reactor. Therefore, the development of a novel method for catalytically converting arylamine and furan is of great significance for the development of efficient synthesis of pyrrole.

This patent reports a new process for the synthesis of pyrroles from aromatic amines and furans. The Lewis acid type metal doped molecular sieve catalyst is utilized for the first time, so that the high efficiency and the high selectivity of the reaction are realized. The Lewis acid catalyst has simple synthesis steps, good stability and high substrate compatibility, and can still exert good catalytic effect in the presence of water. Research on the reaction mechanism shows that under the catalysis of Lewis acid, the reaction does not occur according to the classical Paal-Knorr mechanism, but the direct nucleophilic substitution mechanism of amine on furan ring. In principle, it is also a good complement to the existing bronsted acidic catalytic systems. The development of the method provides a new scheme for constructing green and viable furan synthesis.

Disclosure of Invention

The invention aims to provide a high-efficiency solid Lewis acid catalyst Hf/SBA-15 for catalyzing the condensation reaction of furan compounds and aromatic amines to obtain high-yield N-arylpyrrole.

A method for preparing an N-aryl pyrrole compound is disclosed, wherein the N-aryl pyrrole compound is shown as a general formula C, and a furan compound shown as a general formula A and aromatic amine shown as a general formula B are used as raw materials to react under the catalysis of a solid Lewis acid catalyst to generate the N-aryl pyrrole compound;

。

wherein R is¹，R²，R³，R⁴Each independently selected from one of hydrogen, alkoxy having 1 to 3 carbon atoms, alkyl having 1 to 3 carbon atoms and aryl.

Wherein R is⁵，R⁶，R⁷，R⁸，R⁹Each independently selected from one of hydrogen, alkyl, alkoxy, nitro, cyano, carboxyl and halogen.

Wherein the reaction conditions are as follows: reaction temperature 140-^oAnd C, the reaction time is not less than 6 hours. The molar ratio of the aromatic amine to the furan compound is 1: 3-1: 500, and the reaction is solvent-free reaction or mesitylene is used as a solvent.

The solid Lewis acid catalyst is prepared by adopting a sol-gel method.

The preparation method of the solid Lewis acid catalyst comprises the following steps: weighing a certain mass of polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer P123 in hydrochloric acid, and stirring for a certain time; weighing a certain mass of tetraethyl orthosilicate and a certain mass of hafnium tetrachloride, respectively serving as a silicon source and a hafnium source, adding the tetraethyl orthosilicate and the hafnium tetrachloride into the solution, and continuously stirring for a certain time to obtain a suspension; transferring the obtained suspension into a reaction kettle, and standing at the temperature of 100 ℃ for 24 hours; taking out the reaction kettle, cooling to room temperature, filtering, and washing and filtering with deionized water for three times; and drying the washed filter product in an oven overnight to obtain a catalyst precursor, and calcining the catalyst precursor at the temperature of 450-900 ℃ to obtain the Hf/SBA-15 catalyst.

The solid Lewis acid catalyst Hf/SBA-15 means that because Si in the mesoporous molecular sieve has strong electronegativity, electrons can be transferred from Hf metal center to O and then to silicon, so that the Hf metal center is positively charged, and Lewis acidity of the Hf center is improved.

The invention has the advantages that: the Lewis acidic Hf/SBA-15 catalyst prepared by the sol-gel method can catalyze the amination reaction of furan molecules under mild conditions and obtain the yield of N-arylpyrrole with very high yield, which is the first time that the Lewis acidic catalyst is successfully used in the reaction under such mild conditions, and the mechanism research shows that the reaction is direct nucleophilic substitution of arylamine on furan ring, which is different from the traditional Paal-Knorr reaction observed by using a Bronsted acidic catalyst. Therefore, the invention is a good complement to the existing Bronsted acidic system. On the other hand, compared with the Bronsted acid catalyst, the catalyst shows good water resistance, so that the catalytic system can meet the requirement of industrial production of the N-aryl pyrrole compound, and the economic value of the catalytic system disclosed by the invention is greatly improved.

Drawings

FIG. 1 is a nuclear magnetic characterization chart of the product obtained in example 1 of the present invention.

FIG. 2 shows the ammonia adsorption and desorption (NH) of the catalyst Hf/SBA-15(20) synthesized by the present invention₃-TPD) map.

Detailed Description

The present invention will be further described with reference to the following examples.

The preparation process of the catalyst is as follows: 2g of polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer P123 were weighed out into 75mL of 1.6 mol/L hydrochloric acid and stirred at 40 ℃ for 3 h. 4.25g tetraethylorthosilicate TEOS and several grams HfCl were weighed₄Adding the mixed solution as a silicon source and a hafnium source respectively into the mixed solution, wherein the molar ratio of Si/Hf is (15-30): 1, and continuously stirring the mixed solution for 24 hours at 40 ℃. The resulting suspension was transferred to a reaction kettle and left at 100 ℃ for 24 h. And taking the reaction kettle out of the oven, cooling to room temperature, filtering, and washing with deionized water for three times to obtain the catalyst precursor. The catalyst precursor obtained after the filtration washing was dried overnight in an oven at 100 ℃. The dried catalyst precursor was thoroughly ground and calcined at 550 ℃ for 6h to obtain the Hf/SBA-15 catalyst.

Wherein the Si/Hf ratio of the catalyst with the most excellent catalytic effect is 20:1, and the amount of added hafnium tetrachloride is 0.326g, thereby preparing Hf/SBA-15(20), where 20 in parentheses represents the Si/Hf molar ratio. FIG. 1 shows the ammonia adsorption-desorption diagram of the catalyst Hf/SBA-15(20), from which peaks at 164 ℃ and 313 ℃ can be seen, respectively indicating that the catalyst contains weak acid sites and part of strong acid sites.

Catalysts containing different Si/Hf ratios prepared according to the above method are used to catalyze the reaction of furan compounds with aromatic amines to produce N-arylpyrrole compounds.