Preparation method of 3-methoxy-4-hydroxybenzylamine hydrochloride

Abstract

The invention provides a preparation method of 3-methoxy-4-hydroxybenzylamine hydrochloride. According to the method, 3-methoxy-4-hydroxybenzaldehyde reacts with liquid ammonia and hydrogen at the reaction temperature of 45-50 DEG C with a methanol solvent and a raney nickel catalyst, a product 3-methoxy-4-hydroxybenzylamine is obtained and dissolved in a methanol solvent, the mixture reacts with hydrogen chloride at the room temperature, and 3-methoxy-4-hydroxybenzylamine hydrochloride is obtained. Hydroxylamine hydrochloride in the traditional synthetic process of 3-methoxy-4-hydroxybenzylamine hydrochloride is replaced with the liquid ammonia, the product yield is increased, the adopted raw materials are easy to obtain, the methanol solvent can be recycled, and the raw material cost is reduced.

Description

technical field

[0001] The invention belongs to the technical field of chemical reagent synthesis technology, and in particular relates to a preparation method of 3-methoxy-4-hydroxybenzylamine hydrochloride. Background technique

[0002] 3-Methoxy-4-hydroxybenzylamine hydrochloride is a pharmaceutical intermediate, a key intermediate for the synthesis of natural capsaicinoids and their analogues, and can also be used as a food additive.

[0003] The traditional 3-methoxyl-4-hydroxybenzylamine hydrochloride preparation process mainly contains the following two kinds: one is to synthesize by Leuckart (Leuckart) reaction, but this reaction needs to be carried out under high temperature conditions, and the reaction conversion rate is low The second is to use 3-methoxy-4-hydroxybenzaldehyde to react with hydroxylamine hydrochloride, then through catalytic hydrogenation reaction, and then refine, the synthesis process has low yield and high cost. Contents of the invention [0...

Examples

Embodiment 1

[0021] The present embodiment provides a kind of preparation method of 3-methoxyl-4-hydroxybenzylamine hydrochloride specifically comprising the following steps:

[0022] 1) Dissolve 75g (0.49mol) of 3-methoxy-4-hydroxybenzaldehyde in 200g of anhydrous methanol in advance for later use.

[0023] 2) Pump the 3-methoxy-4-hydroxybenzaldehyde solution ready for use in step 1) into a 1L autoclave, start stirring, add 8g of Raney nickel catalyst, add 220g of anhydrous methanol, and close For all valves in the autoclave, first use vacuum to take away most of the air, and then introduce nitrogen until the pressure in the autoclave reaches 3kg / c㎡, and the pressure does not change. After confirming that the autoclave is well sealed, the nitrogen is discharged, and the operation is repeated 2 to 3 times. , replace all the air in the autoclave with nitrogen.

[0024] 3) Turn on the cooling water in the jacket of the autoclave, control the temperature in the autoclave to below 35°C, add 1...

Embodiment 2

[0033] The present embodiment provides a kind of preparation method of 3-methoxyl-4-hydroxybenzylamine hydrochloride specifically comprising the following steps:

[0034] 1) Dissolve 75g (0.49mol) of 3-methoxy-4-hydroxybenzaldehyde in 150g of anhydrous methanol in advance for later use.

[0035] 2) Pump the 3-methoxyl-4-hydroxybenzaldehyde solution ready for use in step 1) into a 1L autoclave, start stirring, add 6.25g of Raney nickel catalyst, and then add 220g of anhydrous methanol , close all the valves of the autoclave, first take away most of the air with vacuum, and then introduce nitrogen until the pressure in the autoclave reaches 3kg / c㎡, and there is no change in the pressure, confirm that the seal of the autoclave is intact, and then discharge the nitrogen, repeat the operation 2~ Three times, all the air in the autoclave was replaced with nitrogen.

[0036] 3) Turn on the cooling water in the jacket of the autoclave, control the temperature in the autoclave to belo...

Embodiment 3

[0042] 1) Dissolve 75g (0.49mol) of 3-methoxy-4-hydroxybenzaldehyde in 300g of anhydrous methanol in advance for later use.

[0043] 2) Pump the 3-methoxyl-4-hydroxybenzaldehyde solution ready for use in step 1) into a 1L autoclave, start stirring, add 9.4g of Raney nickel catalyst, and then add 220g of anhydrous methanol , close all the valves of the autoclave, first take away most of the air with vacuum, and then introduce nitrogen until the pressure in the autoclave reaches 3kg / c㎡, and there is no change in the pressure, confirm that the seal of the autoclave is intact, and then discharge the nitrogen, repeat the operation 2~ Three times, all the air in the autoclave was replaced with nitrogen.

[0044] 3) Turn on the cooling water in the jacket of the autoclave, control the temperature in the autoclave to below 35°C, add 225g (13.2mol) of liquid ammonia to the autoclave, and the rate of adding liquid ammonia is to control the temperature in the autoclave to below 50°C.

...

technical field

[0001] The invention belongs to the technical field of chemical reagent synthesis technology, and in particular relates to a preparation method of 3-methoxy-4-hydroxybenzylamine hydrochloride. Background technique

[0002] 3-Methoxy-4-hydroxybenzylamine hydrochloride is a pharmaceutical intermediate, a key intermediate for the synthesis of natural capsaicinoids and their analogues, and can also be used as a food additive.

[0003] The traditional 3-methoxyl-4-hydroxybenzylamine hydrochloride preparation process mainly contains the following two kinds: one is to synthesize by Leuckart (Leuckart) reaction, but this reaction needs to be carried out under high temperature conditions, and the reaction conversion rate is low The second is to use 3-methoxy-4-hydroxybenzaldehyde to react with hydroxylamine hydrochloride, then through catalytic hydrogenation reaction, and then refine, the synthesis process has low yield and high cost. Contents of the invention [0...

Examples

Embodiment 1

[0021] The present embodiment provides a kind of preparation method of 3-methoxyl-4-hydroxybenzylamine hydrochloride specifically comprising the following steps:

[0022] 1) Dissolve 75g (0.49mol) of 3-methoxy-4-hydroxybenzaldehyde in 200g of anhydrous methanol in advance for later use.

[0023] 2) Pump the 3-methoxy-4-hydroxybenzaldehyde solution ready for use in step 1) into a 1L autoclave, start stirring, add 8g of Raney nickel catalyst, add 220g of anhydrous methanol, and close For all valves in the autoclave, first use vacuum to take away most of the air, and then introduce nitrogen until the pressure in the autoclave reaches 3kg / c㎡, and the pressure does not change. After confirming that the autoclave is well sealed, the nitrogen is discharged, and the operation is repeated 2 to 3 times. , replace all the air in the autoclave with nitrogen.

[0024] 3) Turn on the cooling water in the jacket of the autoclave, control the temperature in the autoclave to below 35°C, add 1...

Embodiment 2

[0033] The present embodiment provides a kind of preparation method of 3-methoxyl-4-hydroxybenzylamine hydrochloride specifically comprising the following steps:

[0034] 1) Dissolve 75g (0.49mol) of 3-methoxy-4-hydroxybenzaldehyde in 150g of anhydrous methanol in advance for later use.

[0035] 2) Pump the 3-methoxyl-4-hydroxybenzaldehyde solution ready for use in step 1) into a 1L autoclave, start stirring, add 6.25g of Raney nickel catalyst, and then add 220g of anhydrous methanol , close all the valves of the autoclave, first take away most of the air with vacuum, and then introduce nitrogen until the pressure in the autoclave reaches 3kg / c㎡, and there is no change in the pressure, confirm that the seal of the autoclave is intact, and then discharge the nitrogen, repeat the operation 2~ Three times, all the air in the autoclave was replaced with nitrogen.

[0036] 3) Turn on the cooling water in the jacket of the autoclave, control the temperature in the autoclave to belo...

Embodiment 3

[0042] 1) Dissolve 75g (0.49mol) of 3-methoxy-4-hydroxybenzaldehyde in 300g of anhydrous methanol in advance for later use.

[0043] 2) Pump the 3-methoxyl-4-hydroxybenzaldehyde solution ready for use in step 1) into a 1L autoclave, start stirring, add 9.4g of Raney nickel catalyst, and then add 220g of anhydrous methanol , close all the valves of the autoclave, first take away most of the air with vacuum, and then introduce nitrogen until the pressure in the autoclave reaches 3kg / c㎡, and there is no change in the pressure, confirm that the seal of the autoclave is intact, and then discharge the nitrogen, repeat the operation 2~ Three times, all the air in the autoclave was replaced with nitrogen.

[0044] 3) Turn on the cooling water in the jacket of the autoclave, control the temperature in the autoclave to below 35°C, add 225g (13.2mol) of liquid ammonia to the autoclave, and the rate of adding liquid ammonia is to control the temperature in the autoclave to below 50°C.

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