CN109180497B

CN109180497B - Preparation method of N-alkylation product

Info

Publication number: CN109180497B
Application number: CN201811027523.XA
Authority: CN
Inventors: 桑欣欣; 王大伟; 王利魁; 石刚; 倪才华
Original assignee: Jiangnan University
Current assignee: Jiangnan University
Priority date: 2018-09-04
Filing date: 2018-09-04
Publication date: 2020-04-10
Anticipated expiration: 2038-09-04
Also published as: CN109180497A

Abstract

The invention discloses a preparation method of an N-alkylation product, which uses Ni-MOFs material to catalyze aromatic alcohol to react with aniline derivatives to generate the N-alkylation product. The method of the invention does not need solvent, shows high activity and selectivity in the reaction process, and the catalyst is stable in a catalytic system and convenient for recovery and reuse, and the catalytic activity is not obviously reduced after 5 times of reaction.

Description

Preparation method of N-alkylation product

Technical Field

The invention relates to a preparation method of an N-alkylation product, in particular to a method for synthesizing the N-alkylation product by using Ni-MOFs material, belonging to the field of catalysis.

Background

Nitrogen-containing organic substances are one of the essential compounds for life processes, and are important components of living bodies, such as amino acids and nucleotides. Meanwhile, organic nitrogen compounds also hold an important position in pharmaceutical chemistry and organic chemistry. Among nitrogen-containing compounds, amine compounds and derivatives thereof are also important parts, and are widely applied to various industrial and agricultural productions such as pesticides, medicines, dyes, high molecular materials, food additives and the like. The N-alkylation reaction method of alcohol and amine has great superiority from the point of view of atom economy and environmental protection.

Early N-alkylation of alcohols with amines often required very high reaction temperatures and pressures and did not yield very high yields. With the development of metal organic chemistry and alcohol oxidation processes, transition metal catalyzed processes are increasingly being used in the dehydration of N-alkyl alcohols with amines to achieve more desirable reaction results. The transition metal catalyst can greatly reduce the reaction temperature, simplify the experimental operation, effectively accelerate the reaction rate and improve the selectivity of the product. However, most of the transition metals for catalyzing the reaction are noble metals, the preparation process of the catalyst is complex, the cost is high, the catalyst is a homogeneous catalysis system, the used organic solvent is easy to pollute the environment, and the treatment of waste liquid can increase the reaction cost. For example, it has been reported that the Rh complex is a homogeneous catalyst, toluene is used as a solvent, and the yield of the target product is up to 86% (D1: Murat)

Nevin Gürbüz,David Sémeril,and

Eur.j.inorg.chem.2018, 1236-1243). Therefore, there is a need for a process for the preparation of N-alkylated products with green environmental protection, high yield and conversion instead of the existing processes.

Disclosure of Invention

In order to achieve the purpose, the invention provides a preparation method of an N-alkylation product, which takes Ni-MOFs as a catalyst and aromatic alcohol and aniline derivatives as raw materials to react to obtain the N-alkylation product, wherein the reaction formula is as follows:

wherein R1 and R2 are hydrogen, C₁-C₃Alkyl, C substituted by halogen₁-C₃Alkyl, halogen, C₁-C₃Alkoxy, phenyl, and the like; r1 and R2 are preferably hydrogen, methyl, ethyl, n-propyl, n-butyl, trifluoromethyl, F, Cl, Br.

Specifically, the reaction steps are as follows:

(1) aromatic alcohol and aniline derivative in a molar ratio of 2: 1-1: 1, adding Ni-MOFs, adding alkali, and reacting at 80-150 ℃ for 5-24 hours.

(2) And (2) filtering the reaction liquid obtained in the step (1), purifying by using a silica gel column, eluting the product by using petroleum ether, eluting by using an eluent, and removing the solvent to obtain the N-alkylated product. Filtering after the reaction technology, and recovering the catalyst.

The base is a base commonly used in the art, preferably cesium carbonate, potassium hydroxide. The dosage of the alkali is 1 to 1.5 times of the molar ratio of the dosage of the aromatic alcohol. The leacheate is a commonly used leacheate in the field, and the preferred mass ratio is 1: 10 ethyl acetate and petroleum ether.

In the step (1), the reaction temperature is 80-150 ℃, preferably 100-120 ℃.

In the step (1), the reaction time is 5 to 24 hours, preferably 10 to 15 hours.

The Ni-MOFs are crystalline porous framework materials formed by terephthalic acid, trimesic acid, 2-amino terephthalic acid, 2, 5-dihydroxy terephthalic acid and metal nickel salt as ligands, and can be obtained by known literature or a commercially available mode.

In the step (1), the amount of the Ni-MOFs accounts for 1-5% of the mass of the aromatic alcohol.

The method for preparing the N-alkylated product has high yield and conversion rate, and the reaction is carried out under the solvent-free condition, so that the use and the discharge of an organic solvent are reduced compared with the prior art. Meanwhile, the Ni-MOFs material has high cycle stability when used for catalyzing the N-alkylation reaction of the alcohol amine, the catalyst still has high activity after being mechanically applied for 5 times, and the Ni-MOFs material can continuously catalyze the reactions even if mechanical loss is not supplemented and has the same effect.

Detailed Description

The present invention is further illustrated by the following specific examples, which are not to be construed as limiting the invention. All of the starting materials in the examples are commercially available.

Example 1:

to a 50ml Schlenk tube were added benzyl alcohol and aniline 2mmol each, Ni-BDC (H)₂BDC ═ terephthalic acid) 15mg, potassium hydroxide 2mmol, the reaction solution was reacted at 120 ℃ for 10 hours, the mixture was centrifuged, and the centrifuged solution was separated with 200-mesh 300-mesh silica gel column (eluent 1: 10 ethyl acetate/petroleum ether), removing the solvent to obtain the product with the structural formula:

washing the catalyst obtained by centrifuging with ethanol for 3-5 times, drying, repeating the catalytic reaction for 5 times, and ensuring that the product yield is not obviously changed, thereby indicating that the catalyst has good circulation stability.

Example 2:

the catalyst in example 1 was treated with Ni-BTC (H)₃BTC ═ trimesic acid) 15mg, the rest of the conditions being unchanged.

Example 3:

the catalyst of example 1 was treated with Ni-BDC-NH₂(H₂BDC-NH₂2-amino terephthalic acid) 15mg, the remaining conditions being unchanged.

Example 4:

the reaction of 4-methylbenzyl alcohol with aniline, as in example 1, gave the product of the formula:

example 5:

the 4-fluorobenzyl alcohol is reacted with aniline, and the structural formula of the product is obtained in the same way as in example 1:

example 6:

the 2-fluorobenzyl alcohol is reacted with aniline, the catalyst is the catalyst recovered in the embodiment 1, and the structural formula of the product is as follows in the rest embodiment 1:

example 7:

the structural formula of the product is obtained by reacting 2-bromobenzyl alcohol with aniline in the same way as in example 6:

example 8:

4-trifluoromethyl benzyl alcohol is reacted with aniline, and the rest is the same as example 6, to obtain the product with the structural formula:

example 9:

the benzyl alcohol is reacted with 4-methoxyaniline, and the structure formula of the product is obtained in the same manner as in example 6:

example 10:

benzyl alcohol was reacted with 4-fluoroaniline and the remainder of the procedure was as in example 6 to give a product having the formula:

comparative example 1:

the catalyst in example 1 was replaced with 15mg of commercial NiO, with the remainder of the conditions unchanged.

Comparative example 2:

the catalyst in example 1 was replaced with commercial Ni 15mg, with the remainder of the conditions unchanged.

The yields and conversions of the products of the examples, comparative examples and prior art D1 are shown in the table below.

	Yield%	Conversion rate%	Waste liquid
				Example 1	92	100	Is free of
Example 2	85	100	Is free of
				Example 3	95	100	Is free of
Example 4	88	100	Is free of
				Example 5	82	100	Is free of
Example 6	80	100	Is free of
				Example 7	90	100	Is free of
Example 8	87	100	Is free of
				Example 9	81	100	Is free of
Example 10	85	100	Is free of
				Comparative example 1	50	90	Is free of
Comparative example 2	60	90	Is free of
				D1	86	--	Toluene

Claims

1. A method for preparing N-alkylation product, which takes aromatic alcohol and aniline derivative as raw materials to obtain N-alkylation product by catalytic reaction, and is characterized in that: the method takes Ni-MOFs as a catalyst and comprises the following reaction steps:

(1) aromatic alcohol and aniline derivative in a molar ratio of 2: 1-1: 1, adding the mixture into a reaction vessel, adding Ni-MOFs, adding alkali, and reacting for 5-24 hours under the heating condition of 80-150 ℃;

(2) filtering the reaction liquid obtained in the step (1), purifying by using a silica gel column, eluting the product by using petroleum ether, eluting by using an eluent, and removing the solvent to obtain an N-alkylated product;

the reaction formula is as follows:

wherein R1 and R2 are hydrogen, methyl, ethyl, n-propyl, trifluoromethyl, F, Cl, Br;

the alkali is one of cesium carbonate, potassium carbonate or potassium hydroxide, and the dosage of the alkali is 1-1.5 times of the molar ratio of the dosage of the aromatic alcohol; the leacheate is prepared from the following raw materials in a mass ratio of 1: 10 mixtures of ethyl acetate and petroleum ether;

the Ni-MOFs is a crystalline porous framework material formed by terephthalic acid, trimesic acid, 2-amino terephthalic acid or 2, 5-dihydroxy terephthalic acid and metal nickel salt as a ligand;

the amount of the Ni-MOFs accounts for 1-5% of the mass of the aromatic alcohol.