A kind of synthetic method of hydroxybenzylamine

Abstract

A method for synthesizing hydroxybenzylamine belongs to the technical field of organic synthesis. The method principle is: the demethylation reaction of methoxybenzylamine under the action of hydrobromic acid, and the characteristics of the present invention are: under reflux state, methoxybenzylamine and hydrobromic acid are distilled to remove excess moisture to Increase the temperature of reaction, increase the concentration of hydrobromic acid in the reaction mixture, thereby strengthen the demethylation of hydrobromic acid to methoxybenzylamine, and then shorten the reaction time, improve the conversion rate; when no more methyl bromide gas is observed to produce Continue distillation afterward, reclaim excessive hydrobromic acid to further improve temperature of reaction, improve conversion ratio, reduce the consumption of raw material hydrobromic acid simultaneously, can reduce the processing capacity of follow-up step and the consumption of raw material sodium hydroxide again, so the present invention It has the advantages of simple process, short reaction time, easy purification of products, less consumption of raw materials, high reaction yield and the like.

Description

technical field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a synthesis method of hydroxybenzylamine. Background technique

[0002] Hydroxybenzylamine: also known as aminomethylphenol, is an important organic intermediate used in many fields, such as: 2-hydroxybenzylamine has been used in silk dyeing in recent years to treat atherosclerosis and hypertension, etc. Drug research; 3-hydroxybenzylamine is used in the research of hair dyes, antibacterial agents and anti-tumor drugs; 4-hydroxybenzylamine is an important intermediate of the digestive system drug itopride.

[0003] The existing synthetic method of hydroxybenzylamine roughly has the hydroxybenzaldehyde method from raw material; Disadvantages, such as: need high pressure; expensive catalyst; product is not easy to separate and purify, etc. In the methoxybenzylamine method, some people use boron tribromide demethylation method to synthesize hydroxybenzylamine,...

Examples

Embodiment 1

[0040] Embodiment 1: the synthesis of 2-hydroxybenzylamine

[0041] Drop into 252.8 grams (1.5 mole) 48% hydrobromic acid in 0.5L reactor with thermometer, dropping funnel, adjustable power heating mantle, stirrer and distillation unit, utilize dropping funnel under the stirring of stirrer to slowly Add 68.6 grams (0.5 moles) of 2-methoxybenzylamine dropwise, after the dropwise addition, heat up and distill to remove excess water until the top temperature of the distillation reaches more than 120°C (at this time, the temperature in the reactor reaches more than 126°C), and then Reduce the heating rate, make it into a reflux state or distill it out at a very slow rate, keep the temperature in the reactor above 126°C, absorb the generated gas with a solvent or recover it by freezing to protect the environment, until no further gas is observed When the gas is generated, increase the heating rate again, continue distillation, recover excess hydrobromic acid, until the temperature ...

Embodiment 2

[0043] Embodiment 2: the synthesis of 3-hydroxybenzylamine

[0044] Put 708.0 grams (3.5 moles) of 40% hydrobromic acid into a 1L reactor with a thermometer, dropping funnel, adjustable power heating mantle, stirrer and distillation device, and slowly drop it using the dropping funnel under the stirring of the stirrer. Add 137.2 grams (1.0 moles) of 3-methoxybenzylamine, after the dropwise addition, heat up and distill to remove excess water until the distillation temperature reaches above 120°C (at this time, the temperature in the reactor reaches above 126°C), and the heating rate is reduced , make it into a reflux state or distill it off at a very slow rate, keep the temperature in the reactor above 126°C, absorb the generated gas with a solvent or recover it by freezing to protect the environment, until no more gas is observed , increase the heating rate again, continue distillation, reclaim excess hydrobromic acid, stop when the temperature in the reactor reaches more tha...

Embodiment 3

[0046] Embodiment 3: the synthesis of 4-hydroxybenzylamine

[0047] Put 970.9 grams (3.0 moles) of 25% hydrobromic acid into a 1L reactor with a thermometer, dropping funnel, adjustable power heating mantle, stirrer and distillation device, and slowly drop it using the dropping funnel under the stirring of the stirrer. Add 103.7 grams (0.7558 moles) of 4-methoxybenzylamine, after the dropwise addition, heat up and distill to remove excess water until the distillation temperature reaches more than 120°C (at this time, the temperature in the reactor reaches more than 126°C), reduce the heating rate , make it into a reflux state or distill it off at a very slow rate, keep the temperature in the reactor above 126°C, absorb the generated gas with a solvent or recover it by freezing to protect the environment, until no more gas is observed , increase the heating rate again, continue distillation, reclaim excess hydrobromic acid, stop when the temperature in the reactor reaches above...

technical field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a synthesis method of hydroxybenzylamine. Background technique

[0002] Hydroxybenzylamine: also known as aminomethylphenol, is an important organic intermediate used in many fields, such as: 2-hydroxybenzylamine has been used in silk dyeing in recent years to treat atherosclerosis and hypertension, etc. Drug research; 3-hydroxybenzylamine is used in the research of hair dyes, antibacterial agents and anti-tumor drugs; 4-hydroxybenzylamine is an important intermediate of the digestive system drug itopride.

[0003] The existing synthetic method of hydroxybenzylamine roughly has the hydroxybenzaldehyde method from raw material; Disadvantages, such as: need high pressure; expensive catalyst; product is not easy to separate and purify, etc. In the methoxybenzylamine method, some people use boron tribromide demethylation method to synthesize hydroxybenzylamine,...

Examples

Embodiment 1

[0040] Embodiment 1: the synthesis of 2-hydroxybenzylamine

[0041] Drop into 252.8 grams (1.5 mole) 48% hydrobromic acid in 0.5L reactor with thermometer, dropping funnel, adjustable power heating mantle, stirrer and distillation unit, utilize dropping funnel under the stirring of stirrer to slowly Add 68.6 grams (0.5 moles) of 2-methoxybenzylamine dropwise, after the dropwise addition, heat up and distill to remove excess water until the top temperature of the distillation reaches more than 120°C (at this time, the temperature in the reactor reaches more than 126°C), and then Reduce the heating rate, make it into a reflux state or distill it out at a very slow rate, keep the temperature in the reactor above 126°C, absorb the generated gas with a solvent or recover it by freezing to protect the environment, until no further gas is observed When the gas is generated, increase the heating rate again, continue distillation, recover excess hydrobromic acid, until the temperature ...

Embodiment 2

[0043] Embodiment 2: the synthesis of 3-hydroxybenzylamine

[0044] Put 708.0 grams (3.5 moles) of 40% hydrobromic acid into a 1L reactor with a thermometer, dropping funnel, adjustable power heating mantle, stirrer and distillation device, and slowly drop it using the dropping funnel under the stirring of the stirrer. Add 137.2 grams (1.0 moles) of 3-methoxybenzylamine, after the dropwise addition, heat up and distill to remove excess water until the distillation temperature reaches above 120°C (at this time, the temperature in the reactor reaches above 126°C), and the heating rate is reduced , make it into a reflux state or distill it off at a very slow rate, keep the temperature in the reactor above 126°C, absorb the generated gas with a solvent or recover it by freezing to protect the environment, until no more gas is observed , increase the heating rate again, continue distillation, reclaim excess hydrobromic acid, stop when the temperature in the reactor reaches more tha...

Embodiment 3

[0046] Embodiment 3: the synthesis of 4-hydroxybenzylamine

[0047] Put 970.9 grams (3.0 moles) of 25% hydrobromic acid into a 1L reactor with a thermometer, dropping funnel, adjustable power heating mantle, stirrer and distillation device, and slowly drop it using the dropping funnel under the stirring of the stirrer. Add 103.7 grams (0.7558 moles) of 4-methoxybenzylamine, after the dropwise addition, heat up and distill to remove excess water until the distillation temperature reaches more than 120°C (at this time, the temperature in the reactor reaches more than 126°C), reduce the heating rate , make it into a reflux state or distill it off at a very slow rate, keep the temperature in the reactor above 126°C, absorb the generated gas with a solvent or recover it by freezing to protect the environment, until no more gas is observed , increase the heating rate again, continue distillation, reclaim excess hydrobromic acid, stop when the temperature in the reactor reaches above...

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