阅读说明：本技术 一种间甲氧基苯乙胺的制备方法 (Preparation method of m-methoxyphenethylamine ) 是由 唐保清 付志雄 于 2021-08-12 设计创作，主要内容包括：本发明公开一种间甲氧基苯乙胺的制备方法,涉及有机合成制备化学领域。本发明公开的一种间甲氧基苯乙胺的制备方法为：将间甲氧基氯苄加入到氰化物的水溶液中,升温至60～95℃下进行氰化反应,生成间甲氧基氰苄,然后在丙酮中冷却结晶,得到间甲氧基氰苄晶体；再将间甲氧基氰苄晶体和催化剂加入到溶剂中,先通入适量氨气,再通入氢气,在温度110～160℃下进行催化氢化反应,氢化后的产物经减压蒸馏,得到间甲氧基苯乙胺。本发明提供的间甲氧基苯乙胺的制备方法简单,原料易得,过程易控制,成本低廉,并具有收率高、纯度高、环保等特点,适合工业化生产。(The invention discloses a preparation method of m-methoxyphenethylamine, and relates to the field of organic synthesis preparation chemistry. The invention discloses a preparation method of m-methoxyphenethylamine, which comprises the following steps: adding m-methoxy benzyl chloride into an aqueous solution of cyanide, heating to 60-95 ℃ for cyanidation reaction to generate m-methoxy benzyl cyanide, and then cooling and crystallizing in acetone to obtain m-methoxy benzyl cyanide crystals; and adding the m-methoxy cyanobenzyl crystal and a catalyst into a solvent, introducing a proper amount of ammonia gas, introducing hydrogen gas, performing catalytic hydrogenation reaction at the temperature of 110-160 ℃, and distilling the hydrogenated product under reduced pressure to obtain m-methoxy phenylethylamine. The preparation method of m-methoxyphenethylamine provided by the invention is simple, the raw materials are easy to obtain, the process is easy to control, the cost is low, and the method has the characteristics of high yield, high purity, environmental protection and the like, and is suitable for industrial production.)

1. A preparation method of m-methoxyphenethylamine is characterized by comprising the following steps:

(1) adding m-methoxy benzyl chloride into an aqueous solution of cyanide, heating to 60-95 ℃ for cyanidation reaction to generate m-methoxy benzyl cyanide, and then cooling and crystallizing in acetone to obtain m-methoxy benzyl cyanide crystals;

(2) adding the m-methoxy cyanobenzyl crystal and a catalyst into a solvent, introducing a proper amount of ammonia gas, introducing hydrogen gas, performing catalytic hydrogenation reaction at the temperature of 110-160 ℃, and distilling the hydrogenated product under reduced pressure to obtain m-methoxy phenylethylamine.

2. The method for preparing m-methoxyphenethylamine according to claim 1, wherein the reaction temperature during the cyanation reaction is 70 to 85 ℃.

3. The method of claim 1, wherein the molar ratio of the m-methoxybenzyl chloride to the cyanide is 1: 1.01 to 1.1.

4. The method of claim 3, wherein the cyanide is one of sodium cyanide and potassium cyanide.

5. The method of claim 1, wherein the catalyst is one of raney nickel or palladium on carbon.

6. The method for preparing m-methoxyphenethylamine according to claim 1, wherein the solvent is one or two of methanol, toluene and xylene.

7. The method for preparing m-methoxyphenethylamine according to claim 1, wherein the temperature during the hydrogenation reaction is 130 to 140 ℃.

8. The method for preparing m-methoxyphenethylamine according to claim 1, wherein the reaction pressure during the hydrogenation reaction is 0.5 to 4.0 MPa.

9. The method for preparing m-methoxyphenethylamine according to claim 8, wherein the reaction pressure during the hydrogenation reaction is 0.8 to 1.5 MPa.

Technical Field

The invention belongs to the field of organic synthesis preparation chemistry, and particularly relates to a preparation method of m-methoxyphenethylamine.

Background

M-methoxyphenethylamine, chemical name: 3-methoxyphenethylamine. The m-methoxyphenethylamine is used for the Pictet-Spengler reaction catalyzed by perfluorooctane sulfonic acid and is also used for synthesizing 1, 3-oxazepine through the palladium-catalyzed intramolecular coupling reaction. The 1, 3-oxazepine is an important active new medicament and has the effects of resisting convulsion, resisting tumor, improving cerebral ischemia and the like. The market demand of m-methoxyphenethylamine as an indispensable raw material for synthesizing 1, 3-oxazepine is getting larger and larger. At present, no literature report on a synthetic method of m-methoxyphenethylamine exists.

Disclosure of Invention

The invention mainly aims to provide a preparation method of m-methoxyphenethylamine, which has the advantages of low cost, high purity and high yield, and the method has the advantages of simple and easily obtained raw materials, easy operation and suitability for mass production.

In order to realize the purpose of the invention, the invention provides a preparation method of m-methoxyphenethylamine, which specifically comprises the following steps:

(1) adding m-methoxy benzyl chloride into an aqueous solution of cyanide, heating to 60-95 ℃ for cyanidation reaction to generate m-methoxy benzyl cyanide, and then cooling and crystallizing in acetone to obtain m-methoxy benzyl cyanide crystals;

(2) adding the m-methoxy cyanobenzyl crystal and a catalyst into a solvent, introducing a proper amount of ammonia gas, introducing hydrogen gas, performing catalytic hydrogenation reaction at the temperature of 110-160 ℃, and distilling the hydrogenated product under reduced pressure to obtain m-methoxy phenylethylamine.

Further, the reaction temperature in the cyanidation reaction process is 70-85 ℃.

Further, the molar ratio of the m-methoxy benzyl chloride to the cyanide is 1: 1.01 to 1.1.

Further, the cyanide is one of sodium cyanide and potassium cyanide.

Further, the catalyst is one of raney nickel or palladium carbon.

Further, the solvent is one or two of methanol, toluene and xylene.

Further, the temperature in the hydrogenation reaction process is 130-140 ℃.

Further, the reaction pressure in the hydrogenation reaction process is 0.5-4.0 MPa.

Further, the reaction pressure in the hydrogenation reaction process is 0.8-1.5 MPa.

The invention achieves the following beneficial effects:

the method comprises the steps of carrying out cyanidation reaction on m-methoxy benzyl chloride and cyanide to generate m-methoxy benzyl cyanide, then cooling and crystallizing in acetone to obtain m-methoxy benzyl cyanide crystals, and carrying out catalytic hydrogenation reaction on the m-methoxy benzyl cyanide crystals in a solvent to obtain m-methoxy phenethylamine. The preparation method is simple, the raw materials are easy to obtain, the process is easy to control, the cost is low, and the method has the characteristics of high yield (the yield can reach more than 92%), high purity (the purity can reach more than 99.1%), environmental protection and the like, and is suitable for industrial production.

Drawings

FIG. 1 is a schematic diagram of the cyanidation reaction of the process for producing m-methoxyphenethylamine of the present invention;

FIG. 2 is a schematic diagram showing the procedure of the hydrogenation reaction in the process for producing m-methoxyphenethylamine according to the present invention.

Detailed Description

The technical solutions in the embodiments of the present invention are clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

A preparation method of m-methoxyphenethylamine, the reaction process of which is schematically shown in figure 1 and figure 2, comprises the following steps:

(1) cyanation reaction, as shown in FIG. 1: adding water into sodium cyanide or potassium cyanide, then adding m-methoxy benzyl chloride, heating to 60-95 ℃ for cyanidation, cooling and layering, taking the lower oil layer, adding acetone, cooling, crystallizing and centrifuging to obtain m-methoxy benzyl cyanide crystals.

(2) And (2) performing hydrogenation reaction, as shown in figure 2, mixing the m-methoxy cyanobenzyl crystal, a catalyst Raney nickel or palladium carbon and a solvent, introducing a proper amount of ammonia gas, introducing hydrogen gas, performing catalytic hydrogenation reaction at the temperature of 110-160 ℃ and the pressure of 0.5-4.0 MPa, and performing reduced pressure distillation on a hydrogenated product to obtain the m-methoxy phenylethylamine.

The solvent is one or two of methanol, toluene and xylene.

The process for producing m-methoxyphenethylamine according to the present invention will be described below with reference to specific examples.

Example 1:

the preparation method of m-methoxyphenethylamine comprises the following steps:

(1) cyanidation reaction

Adding 49.5g (1.01mol) of sodium cyanide into a 500ml four-neck flask with a condenser and stirring, adding 110g of water, heating to 70 ℃, dropwise adding 156.6g (1.0mol) of m-methoxy benzyl chloride into the flask for 2 hours, after the addition is finished, heating to 70-80 ℃, preserving the temperature for 4 hours, cooling to about 50 ℃, layering, adding 90g of acetone into a lower oil layer, cooling to-5-2 ℃, crystallizing, and centrifuging to obtain 135.3g of m-methoxy benzyl cyanide crystals with the product yield of 92%. The acetone mother liquor is distilled and recycled for reuse. Collecting and barreling the upper cyanide water layer, adding the upper cyanide water layer into a high-pressure reaction kettle, adding a proper amount of sodium hydroxide, heating to 130-140 ℃, keeping the temperature for 8-10 hours, detecting the concentration of cyanide, and cooling and discharging after reaching the standard.

(2) Hydrogenation reaction

294g (2.0mol) of m-methoxy cyanobenzyl crystals, 850ml of methanol and 35g of Raney nickel catalyst are put into a 2000ml high-pressure reaction kettle, 210g of ammonia gas is introduced, the temperature is raised to 130 ℃, hydrogen gas is slowly introduced for about 12 hours, the pressure in the reaction kettle is maintained at 0.8MPa, when the pressure in the reaction kettle is not reduced, the temperature and the pressure are maintained for 2 hours, the reaction is finished, the reaction is cooled, the pressure is relieved, the catalyst is removed by suction filtration, and after the methanol solvent is removed, the reduced pressure distillation is carried out to obtain 278.3g of m-methoxy phenylethylamine with the content of 99.2 percent and the product yield of 92 percent.

Example 2

The preparation method of m-methoxyphenethylamine comprises the following steps:

(1) cyanidation reaction

Adding 51.5g (1.05mol) of sodium cyanide into a 500ml four-neck flask with a condenser and stirring, adding 110g of water, heating to 70 ℃, dropwise adding 156.6g (1.0mol) of m-methoxy benzyl chloride into the flask for 2 hours, after the addition is finished, heating to 75-85 ℃, preserving the temperature for 4 hours, cooling to about 50 ℃, layering, adding 90g of acetone into a lower oil layer, cooling to-5-2 ℃, crystallizing, and centrifuging to obtain 136g of m-methoxy benzyl cyanide crystals, wherein the product yield is 92.5%. The acetone mother liquor is distilled and recycled for reuse. Collecting and barreling the upper cyanide water layer, adding the upper cyanide water layer into a high-pressure reaction kettle, adding a proper amount of sodium hydroxide, heating to 130-140 ℃, keeping the temperature for 8-10 hours, detecting the concentration of cyanide, and cooling and discharging after reaching the standard.

(2) Hydrogenation reaction

294g (2.0mol) of m-methoxy cyanobenzyl crystals, 900ml of toluene and 35g of Raney nickel catalyst are put into a 2000ml high-pressure reaction kettle, 200g of ammonia gas is introduced, the temperature is raised to 140 ℃, hydrogen gas is slowly introduced for about 12 hours, the pressure in the reaction kettle is maintained at 1.2MPa, when the pressure in the reaction kettle is not reduced, the temperature and the pressure are maintained for 2 hours, the reaction is finished, the reaction is cooled, the pressure is relieved, the catalyst is removed by suction filtration, and after the toluene solvent is removed, the reduced pressure distillation is carried out to obtain 280.4g of m-methoxy phenylethylamine with the content of 99.3 percent and the product yield of 92.7 percent.

Example 3

The preparation method of m-methoxyphenethylamine comprises the following steps:

(1) cyanidation reaction

Adding 53.9g (1.1mol) of sodium cyanide into a 500ml four-neck flask with a condenser and stirring, adding 115g of water, heating to 75 ℃, dropwise adding 156.6g (1.0mol) of m-methoxy benzyl chloride into the flask for 2 hours, after the addition is finished, heating to 75-85 ℃, preserving the temperature for 4 hours, cooling to about 50 ℃, layering, adding 90g of acetone into a lower oil layer, cooling to-5-2 ℃, crystallizing, and centrifuging to obtain 135.5g of m-methoxy benzyl cyanide crystals, wherein the product yield is 92.2%. The acetone mother liquor is distilled and recycled for reuse. Collecting and barreling the upper cyanide water layer, adding the upper cyanide water layer into a high-pressure reaction kettle, adding a proper amount of sodium hydroxide, heating to 130-140 ℃, keeping the temperature for 8-10 hours, detecting the concentration of cyanide, and cooling and discharging after reaching the standard.

(2) Hydrogenation reaction

294g (2.0mol) of m-methoxy cyanobenzyl crystals, 850ml of xylene and 35g of Raney nickel catalyst are put into a 2000ml high-pressure reaction kettle, 210g of ammonia gas is introduced, the temperature is raised to 130 ℃, hydrogen gas is slowly introduced for about 12 hours, the pressure in the reaction kettle is maintained at 1.5MPa, the pressure in the reaction kettle is kept for 3 hours after the pressure in the reaction kettle is not reduced, the reaction is finished, the reaction is cooled, the pressure is relieved, the catalyst is removed by suction filtration, and after the xylene solvent is removed, 278.2g of m-methoxy phenylethylamine with the content of 99.1 percent and the product yield of 92.1 percent is obtained by reduced pressure distillation.

Example 4

The preparation method of m-methoxyphenethylamine comprises the following steps:

(1) cyanidation reaction

Adding 51.5g (1.05mol) of sodium cyanide into a 500ml four-neck flask with a condenser and stirring, adding 110g of water, heating to 70 ℃, dropwise adding 156.6g (1.0mol) of m-methoxy benzyl chloride into the flask for 2 hours, after the addition is finished, heating to 70-80 ℃, preserving the temperature for 4 hours, cooling to about 50 ℃, layering, adding 90g of acetone into a lower oil layer, cooling to-5-2 ℃, crystallizing, and centrifuging to obtain 135.2g of m-methoxy benzyl cyanide crystals, wherein the product yield is 92%. The acetone mother liquor is distilled and recycled for reuse. Collecting and barreling the upper cyanide water layer, adding the upper cyanide water layer into a high-pressure reaction kettle, adding a proper amount of sodium hydroxide, heating to 130-140 ℃, keeping the temperature for 8-10 hours, detecting the concentration of cyanide, and cooling and discharging after reaching the standard.

(2) Hydrogenation reaction

294g (2.0mol) of m-methoxy cyanobenzyl crystals, 850ml of methanol and 3.5g of 5% palladium-carbon catalyst are put into a 2000ml high-pressure reaction kettle, 200g of ammonia gas is introduced, the temperature is raised to 140 ℃, hydrogen gas is slowly introduced for about 12 hours, the pressure in the reaction kettle is maintained at 1.3MPa, the pressure in the reaction kettle is not reduced, the temperature and the pressure are maintained for 3 hours again after the pressure in the reaction kettle is not reduced, the reaction is finished, the reaction is cooled, the pressure is relieved, the catalyst is removed by suction filtration, and the reduced pressure distillation is carried out after the methanol solvent is removed, so that 278.3g of m-methoxy phenylethylamine with the content of 99.2% and the product yield of 92% are obtained.

Example 5

The preparation method of m-methoxyphenethylamine comprises the following steps:

(1) cyanidation reaction

Adding 65.7g (1.01mol) of potassium cyanide into a 500ml four-neck flask with a condenser and stirring, adding 110g of water, heating to 75 ℃, dropwise adding 156.6g (1.0mol) of m-methoxy benzyl chloride into the flask for 2 hours, after the addition is finished, heating to 70-80 ℃, preserving the temperature for 4 hours, cooling to about 50 ℃, layering, adding 90g of acetone into a lower oil layer, cooling to-5-2 ℃, crystallizing, and centrifuging to obtain 136g of m-methoxy benzyl cyanide crystals, wherein the product yield is 92.5%. The acetone mother liquor is distilled and recycled for reuse. Collecting and barreling the upper cyanide water layer, adding the upper cyanide water layer into a high-pressure reaction kettle, adding a proper amount of sodium hydroxide, heating to 130-140 ℃, keeping the temperature for 8-10 hours, detecting the concentration of cyanide, and cooling and discharging after reaching the standard.

(2) Hydrogenation reaction

294g (2.0mol) of m-methoxy cyanobenzyl crystals, 850ml of methanol and 3.5g of 5% palladium-carbon catalyst are put into a 2000ml high-pressure reaction kettle, 200g of ammonia gas is introduced, the temperature is raised to 130 ℃, hydrogen gas is slowly introduced for about 12 hours, the pressure in the reaction kettle is maintained at 0.8MPa, the pressure in the reaction kettle is kept constant for 3 hours after the pressure in the reaction kettle is not reduced, the reaction is finished, the reaction is cooled, the pressure is relieved, the catalyst is removed by suction filtration, and after the methanol solvent is removed, the reduced pressure distillation is carried out to obtain 278.5g of m-methoxy phenethylamine with the content of 99.3% and the product yield of 92.2%.

Example 6

The preparation method of m-methoxyphenethylamine comprises the following steps:

(1) cyanidation reaction

Adding 68.2g (1.05mol) of potassium cyanide into a 500ml four-neck flask with a condenser and stirring, adding 110g of water, heating to 75 ℃, dropwise adding 156.6g (1.0mol) of m-methoxy benzyl chloride into the flask for 2 hours, after the addition is finished, heating to 75-85 ℃, preserving the temperature for 4 hours, cooling to about 50 ℃, layering, adding 90g of acetone into a lower oil layer, cooling to-5-2 ℃, crystallizing, and centrifuging to obtain 135.7g of m-methoxy benzyl cyanide crystals, wherein the product yield is 92.3%. The acetone mother liquor is distilled and recycled for reuse. Collecting and barreling the upper cyanide water layer, adding the upper cyanide water layer into a high-pressure reaction kettle, adding a proper amount of sodium hydroxide, heating to 130-140 ℃, keeping the temperature for 8-10 hours, detecting the concentration of cyanide, and cooling and discharging after reaching the standard.

(2) Hydrogenation reaction

294g (2.0mol) of m-methoxy cyanobenzyl crystals, 900ml of toluene and 3.5g of 5% palladium-carbon catalyst are put into a 2000ml high-pressure reaction kettle, 210g of ammonia gas is introduced, the temperature is raised to 140 ℃, hydrogen is slowly introduced for about 13 hours, the pressure in the reaction kettle is maintained at 1.2MPa, the pressure in the reaction kettle is kept for 3 hours when the pressure is not reduced, the reaction is finished, the reaction is cooled, the pressure is relieved, the catalyst is removed by suction filtration, and after the toluene solvent is removed, the reduced pressure distillation is carried out to obtain 279.4g of m-methoxy phenylethylamine with the content of 99.5% and the product yield of 92.5%.

Example 7

The preparation method of m-methoxyphenethylamine comprises the following steps:

(1) cyanidation reaction

Adding 71.5g (1.1mol) of potassium cyanide into a 500ml four-neck flask with a condenser and stirring, adding 110g of water, heating to 70 ℃, dropwise adding 156.6g (1.0mol) of m-methoxy benzyl chloride into the flask for 2 hours, after the addition is finished, heating to 70-80 ℃, preserving the temperature for 4 hours, cooling to about 50 ℃, layering, adding 90g of acetone into a lower oil layer, cooling to-5-2 ℃, crystallizing, and centrifuging to obtain 135.5g of m-methoxy benzyl cyanide crystals, wherein the product yield is 92.2%. The acetone mother liquor is distilled and recycled for reuse. Collecting and barreling the upper cyanide water layer, adding the upper cyanide water layer into a high-pressure reaction kettle, adding a proper amount of sodium hydroxide, heating to 130-140 ℃, keeping the temperature for 8-10 hours, detecting the concentration of cyanide, and cooling and discharging after reaching the standard.

(2) Hydrogenation reaction

294g (2.0mol) of m-methoxy cyanobenzyl crystals, 900ml of xylene and 3.5g of 5% palladium-carbon catalyst are put into a 2000ml high-pressure reaction kettle, 210g of ammonia gas is introduced, the temperature is raised to 130 ℃, hydrogen gas is slowly introduced for about 13 hours, the pressure in the reaction kettle is maintained at 1.5MPa, the pressure in the reaction kettle is not reduced, the temperature and the pressure are maintained for 3 hours again after the pressure in the reaction kettle is not reduced, the reaction is finished, the reaction is cooled, the pressure is relieved, the catalyst is removed by suction filtration, and after a toluene solvent is removed, the reduced pressure distillation is carried out to obtain 278.3g of m-methoxy phenylethylamine with the content of 99.3%, and the product yield is 92%.

The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope of the present invention are included in the scope of the present invention.