CN-116574043-B - Preparation method of 2, 5-dimethyl-N-aryl pyrrole

Abstract

The invention discloses a preparation method of 2, 5-dimethyl-N-aryl pyrrole, which takes 2, 5-hexanedione and nitroarene as raw materials, and the 2, 5-dimethyl-N-aryl pyrrole is prepared by reaction in a reaction solvent under the action of a supported double-metal double-function catalyst in a hydrogen atmosphere. The supported bi-metal bi-functional catalyst comprises a carrier and an effective active ingredient supported on the carrier, wherein the carrier is one of silicon dioxide (SiO 2 ), titanium oxide (TiO 2 ) and Active Carbon (AC), and the effective active ingredient comprises oxides of nickel and manganese. The yield of the 2, 5-dimethyl-N-aryl pyrrole synthesized by the method is more than 90 percent. The method has the advantages of simple process, recoverable catalyst, high reaction selectivity, high product yield and obvious industrial production advantage.

Inventors

• LIU YINGXIN
• WU HAIMEI
• WANG JIALE
• WANG JUN
• WEI ZUOJUN

Assignees

• 浙江工业大学

Dates

Publication Date

20260505

Application Date

20230428

Claims (9)

1. 1. The preparation method of the 2, 5-dimethyl-N-aryl pyrrole is characterized in that 2, 5-hexanedione and nitroarene are used as raw materials, and the 2, 5-dimethyl-N-aryl pyrrole is prepared by utilizing a one-pot cascade reaction in a reaction solvent under the action of a supported double-metal double-function catalyst in a hydrogen atmosphere; The supported bi-metal bi-functional catalyst comprises a carrier and an effective active ingredient supported on the carrier, wherein the carrier is one of alumina, silica or titania, and the effective active ingredient comprises oxides of nickel metal and manganese; in the supported bi-metal bi-functional catalyst, the molar ratio of nickel to manganese is 1:1 or 2:1; The nickel metal loading capacity of the supported bi-metal bi-functional catalyst is 1-3wt%; The mass ratio of the nitroarene to the supported bimetallic bifunctional catalyst is 1:0.01-0.6; the reaction solvent is methanol, ethanol, toluene, water or tetrahydrofuran, and the volume dosage of the solvent is 2-50 mL/g based on the mass of 2, 5-hexanedione.
2. 2. The preparation method of 2, 5-dimethyl-N-aryl pyrrole according to claim 1, wherein the mass ratio of nitroarene to supported double-metal bifunctional catalyst is 1:0.02-0.5.
3. 3. The method for preparing 2, 5-dimethyl-N-aryl pyrrole according to claim 1, wherein the molar ratio of 2, 5-hexanedione to nitroaromatic hydrocarbon is 3:1-1:1.
4. 4. The method for preparing 2, 5-dimethyl-N-aryl pyrrole according to claim 1, wherein the volume amount of the solvent is 5-30 mL/g based on the mass of 2, 5-hexanedione.
5. 5. The method for preparing 2, 5-dimethyl-N-aryl pyrrole according to claim 1, wherein the reaction conditions are that the hydrogen pressure is 0.2-5 MPa and the reaction is carried out for 0.1-15 h at 50-180 ℃.
6. 6. The method for preparing 2, 5-dimethyl-N-arylpyrrole according to claim 5, wherein the reaction condition is that the hydrogen pressure is 0.3-3.0 MPa, the reaction temperature is 70-120 ℃, and the reaction time is 8-15 h.
7. 7. The preparation method of the 2, 5-dimethyl-N-aryl pyrrole according to claim 1 is characterized in that after the reaction is finished, the post-treatment is further carried out, the method comprises the steps of carrying out suction filtration on a reaction liquid, recovering and reusing a filter cake which is a supported double-function catalyst, removing a solvent from filtrate by distillation, and separating residues by column chromatography to obtain the product 2, 5-dimethyl-N-aryl pyrrole.
8. 8. The preparation method of the 2, 5-dimethyl-N-arylpyrrole is characterized by comprising the steps of roasting a carrier at 300-600 ℃ for 3-8 hours, immersing the roasted carrier in a mixed aqueous solution of manganese salt and nickel salt, drying at 80-150 ℃ after soaking, and introducing reducing gas at 200-800 ℃ for reduction, so that the supported bimetal bifunctional catalyst is prepared.
9. 9. The method for preparing 2, 5-dimethyl-N-aryl pyrrole according to claim 8, wherein the nickel salt is one of nickel nitrate, nickel acetate or nickel chloride, and the manganese salt is one of manganese acetate or manganese nitrate.

Description

Preparation method of 2, 5-dimethyl-N-aryl pyrrole Technical Field The invention relates to the technical field of pharmaceutical chemicals, in particular to a method for preparing N-aryl pyrrole by one-pot cascade reaction of 2, 5-hexanedione and nitroaromatic hydrocarbon. Background N-aryl pyrrole is an important nitrogen heterocyclic compound, and has various biological activities and important medicinal values. Therefore, there is a great interest in developing synthetic methods for accurately constructing pyrrole rings. The current synthesis methods of N-aryl pyrrole mainly comprise a Hantzsch method, a Clauson-Kaas method, a Paal-Knorr method and the like. Among them, the Paal-Knorr method is considered one of the most attractive and efficient synthetic methods. The Paal-Knorr method is to prepare N-aryl pyrrole through condensation reaction of 1, 4-dicarbonyl compound and aniline compound. It is well known that aniline compounds can be prepared from the corresponding nitroaromatics by catalytic hydrogenation. Therefore, in the reaction of constructing the N-aryl pyrrole by adopting the Paal-Knorr method, nitroarene is used as a starting material to replace aniline, and the N-aryl pyrrole is prepared by one-pot hydrogenation/condensation cascade reaction of the 1, 4-dicarbonyl compound and the nitroarene, so that the N-aryl pyrrole is more economical and environment-friendly. The other raw material 1, 4-dicarbonyl compound for preparing the N-aryl pyrrole by adopting the method can select 2, 5-hexanedione (2, 5-HD). The 2,5-HD can be obtained by converting lignocellulose which is a renewable resource, and can realize sustainable preparation of N-aryl pyrrole by taking the lignocellulose as a starting material, thereby being more in line with the requirements of green chemistry. The key to realizing the accurate synthesis of N-aryl pyrrole by the one-pot cascade reaction of 2,5-HD and nitroarene is the design and preparation of the efficient bifunctional catalyst. In the reaction, the metal catalyst is required to hydrogenate and reduce the nitroarene into the aniline compound, and the acid catalyst is required to promote the condensation reaction of the 2,5-HD and the generated aniline compound to finally obtain the N-aryl pyrrole. Literature (CHEMCATCHEM 2013,5,538-549) reports the synthesis of N-aryl pyrroles by the reaction of 2,5-HD with nitroarenes using a bifunctional MOF material containing both a metal active center Pd (or Pt) and a lewis acid Cr 3+ site as a catalyst. Toluene is used as a solvent, and the yield of the 2, 5-dimethyl-N-phenylpyrrole is 99% after the reaction for 5h under the hydrogen pressure of 110 ℃ and 0.5 MPa. However, pd (or Pt) is expensive and scarce in source and is not suitable for large-scale use. Literature (angel. Chem. Int. Ed.2020,59,18679-18685 ) reports that the cobalt/cobalt oxide core-shell particles (Co/NGr-c@sio 2 -L) coated with nitrogen doped graphene supported on SiO 2 are used as catalysts to prepare 2, 5-dimethyl-N-arylpyrrole by a one-pot cascade reaction of 2,5-HD with nitroarene, the highest yield of 24H,2, 5-dimethyl-N-arylpyrrole is 88% at 120 ℃ under 4MPa hydrogen pressure, but in this system the reaction temperature is higher, the pressure of H 2 used is greater and the yield is lower. Literature (j.catalyst.2022,416, 39-46) reports the preparation of 2, 5-dimethyl-N-arylpyrrole by one-pot cascade of 2,5-HD and nitroaromatic hydrocarbons with fe@nsic as catalyst and HCOOH as reducing agent, with a maximum yield of 87% for 2, 5-dimethyl-N-arylpyrrole at 100 ℃. However, the system still has the defects of long reaction time and low yield. Disclosure of Invention Aiming at the technical problems existing in the prior art, the invention aims to provide a preparation method of 2, 5-dimethyl-N-aryl pyrrole. The invention provides an environment-friendly method for precisely synthesizing 2, 5-dimethyl-N-aryl pyrrole by using H 2 as a reducing agent and adopting a one-pot cascade reaction of 2, 5-hexanedione (2, 5-HD) and nitroarene under the action of a supported bimetal bifunctional catalyst. The method for preparing 2, 5-dimethyl-N-aryl pyrrole by cascade reaction of 2, 5-hexanedione and nitroarene in one pot comprises the steps of taking 2,5-HD shown in a formula I and nitroarene shown in a formula II as starting materials, reacting in a reaction solvent under the action of a supported double-metal bifunctional catalyst in a hydrogen atmosphere, and performing post-treatment after the reaction is finished to obtain the 2, 5-dimethyl-N-aryl pyrrole shown in a formula III, wherein the reaction formula is shown as follows: in the formula II and the formula III, the substituent R is C1-C4 alkyl, C1-C4 alkoxy or halogen. Further, the supported bi-metal bi-functional catalyst comprises a carrier and an effective active ingredient supported on the carrier, wherein the carrier is one of active carbon, mesoporous carbon, diatomite, ZSM-5, alumina, silica or t