CN105061231A - Preparation method of 3-methoxy-4-hydroxybenzylamine hydrochloride - Google Patents
Preparation method of 3-methoxy-4-hydroxybenzylamine hydrochloride Download PDFInfo
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- CN105061231A CN105061231A CN201510494807.XA CN201510494807A CN105061231A CN 105061231 A CN105061231 A CN 105061231A CN 201510494807 A CN201510494807 A CN 201510494807A CN 105061231 A CN105061231 A CN 105061231A
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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
The invention belongs to chemical reagent synthesis technology field, be specifically related to the preparation method of a kind of 3-methoxyl group-4-Hydrobenzylamine hydrochloride.
Background technology
3-methoxyl group-4-Hydrobenzylamine hydrochloride is medicine intermediate, is the key intermediate of synthesis of natural Capsaicinoids and analogue thereof, also can be used as foodstuff additive simultaneously.
It is by Liu Kate (Leuckart) Reactive Synthesis that traditional 3-methoxyl group-4-Hydrobenzylamine hydrochloride preparation technology mainly contains following two kinds: one, but this reaction needed is carried out under the high temperature conditions, and reaction conversion ratio is low; Two is adopt Vanillin and oxammonium hydrochloride to react, and then through catalytic hydrogenation reaction, re-refines, and this synthesis technique yield is low, and cost is high.
Summary of the invention
The object of the invention is to overcome the problem that existing 3-methoxyl group-4-Hydrobenzylamine hydrochloride synthesis technique yield is low, cost is high.
For this reason, the invention provides the preparation method of a kind of 3-methoxyl group-4-Hydrobenzylamine hydrochloride, by Vanillin at solvent methanol, catalyzer Raney's nickel, obtain product 3-methoxyl group-4-Hydrobenzylamine with liquefied ammonia, hydrogen reaction under temperature of reaction 45 ~ 50 DEG C of conditions, then product 3-methoxyl group-4-Hydrobenzylamine is dissolved in methanol solvate and at room temperature obtains 3-methoxyl group-4-Hydrobenzylamine hydrochloride with hcl reaction.
The preparation method of this 3-methoxyl group-4-Hydrobenzylamine hydrochloride specifically comprises the steps:
1) be dissolved in anhydrous methanol by Vanillin, the mass ratio of Vanillin and anhydrous methanol is 1:4 ~ 1:2;
2) by step 1) in dissolve Vanillin solution suction autoclave in, stirring adds Raney's nickel catalyst, the Raney's nickel catalyst added and the mass ratio of Vanillin are 1:12 ~ 1:8, go out the air in autoclave with nitrogen replacement;
3) control below high pressure temperature in the kettle to 35 DEG C, in autoclave, add liquefied ammonia, the quality of liquefied ammonia is 1 ~ 3 times of Vanillin;
4) after liquefied ammonia adds, in autoclave, pass into hydrogen, open hydrogen recycle machine, be warming up to 45 ~ 50 DEG C of reactions, until Vanillin reacts completely;
5) high pressure temperature in the kettle is down to less than 40 DEG C, the material that pressure release is taken out in autoclave is dissolved in methyl alcohol, and the mass ratio of methyl alcohol and Vanillin is 2:1 ~ 3:1, crosses and filters Raney's nickel catalyst;
6) by step 5) filtrate be down to room temperature, in filtrate, pass into hydrogen chloride gas to pH=1, filter and collect solids and dries to obtain 3-methoxyl group-4-Hydrobenzylamine hydrochloride finished product.
Above-mentioned Raney's nickel catalyst be activated after Raney's nickel.
Above-mentioned steps 2) in nitrogen replacement autoclave the detailed process of air for closing all valves of autoclave, first take away most of air by vacuum, then pass into nitrogen and reach 3kg/c ㎡ to autoclave internal pressure, and pressure unchanged after by nitrogen discharge, repetitive operation 2 ~ 3 times.
Above-mentioned steps 3) in the interpolation speed control high pressure temperature in the kettle of liquefied ammonia be less than 50 DEG C.
Beneficial effect of the present invention:
(1) preparation method of this 3-methoxyl group-4-Hydrobenzylamine hydrochloride provided by the invention adopts liquefied ammonia to substitute oxammonium hydrochloride in traditional 3-methoxyl group-4-Hydrobenzylamine hydrochloride synthesis technique, adopts Raney's nickel to make catalyzer, improves yield.
(2) raw material adopted in the preparation method of this 3-methoxyl group-4-Hydrobenzylamine hydrochloride provided by the invention is cheap and easy to get, and the recyclable recycling of methanol solvate, reduces raw materials cost.
(3) preparation method of this 3-methoxyl group-4-Hydrobenzylamine hydrochloride provided by the invention is simple to operate, and the by product of generation is conveniently separated removing, and Product Precision is high.
Embodiment
Embodiment 1:
The preparation method present embodiments providing a kind of 3-methoxyl group-4-Hydrobenzylamine hydrochloride specifically comprises the steps:
1) Vanillin of 75g (0.49mol) is dissolved in the anhydrous methanol of 200g for subsequent use in advance.
2) by step 1) in the autoclave of Vanillin solution for standby material suction 1L that dissolved, start to stir, add the Raney's nickel catalyst of 8g, add 220g anhydrous methanol, close all valves of autoclave, first take away most of air by vacuum, then pass into nitrogen and reach 3kg/c ㎡ to autoclave internal pressure, and the sealing of pressure unchanged confirmation autoclave intact after by nitrogen discharge, repetitive operation 2 ~ 3 times, goes out the whole air in autoclave with nitrogen replacement.
3) open autoclave chuck temperature lowering water, control below high pressure temperature in the kettle to 35 DEG C, in autoclave, add 100g (5.88mol) liquefied ammonia, the interpolation speed of liquefied ammonia is less than 50 DEG C for controlling high pressure temperature in the kettle, and within about about 30 minutes, logical ammonia terminates.
4), after liquefied ammonia adds, close logical ammonia section door, open hydrogen section door, in autoclave, pass into hydrogen, hydrogen pressure progressively raises, and reaches 8kg/c ㎡, put hydrogen section door into, open hydrogen recycle machine, be warming up to 45 ~ 50 DEG C of reactions, now hydrogen pressure 8 ~ 10kg/c ㎡ in autoclave, hydrogen pressure can decline very soon, then continue logical hydrogen, until in autoclave in hydrogen pressure about 1.5 hours without considerable change, illustrate that Vanillin hydrogenation is complete.
Above-mentioned Vanillin reaction principle is as follows:
5) after Vanillin reacts completely, high pressure temperature in the kettle is down to less than 40 DEG C, the material that pressure release is taken out in autoclave is dissolved in 150g methyl alcohol, diluted material, filter the Raney's nickel catalyst in removing material, catalyzer completely cuts off air containment and preserves, and can reuse, and filtrate air distillation is reclaimed methyl alcohol 340g and can recirculation be used.
6) by step 5) filtrate after air distillation process is down to room temperature, hydrogen chloride gas is passed into pH=1 in filtrate, solids is collected in filtration dries to obtain 3-methoxyl group-4-Hydrobenzylamine hydrochloride finished product 85g (0.45mol), and its reaction principle is as follows:
Can obtain 3-methoxyl group in the present embodiment-4-Hydrobenzylamine hydrochloride building-up reactions yield is as calculated 91%.
Embodiment 2:
The preparation method present embodiments providing a kind of 3-methoxyl group-4-Hydrobenzylamine hydrochloride specifically comprises the steps:
1) Vanillin of 75g (0.49mol) is dissolved in the anhydrous methanol of 150g for subsequent use in advance.
2) by step 1) in the autoclave of Vanillin solution for standby material suction 1L that dissolved, start to stir, add the Raney's nickel catalyst of 6.25g, add 220g anhydrous methanol again, close all valves of autoclave, first take away most of air by vacuum, then pass into nitrogen and reach 3kg/c ㎡ to autoclave internal pressure, and the sealing of pressure unchanged confirmation autoclave intact after nitrogen is discharged, repetitive operation 2 ~ 3 times, goes out the whole air in autoclave with nitrogen replacement.
3) open autoclave chuck temperature lowering water, control below high pressure temperature in the kettle to 35 DEG C, in autoclave, add 75g (4.4mol) liquefied ammonia, the interpolation speed of liquefied ammonia is less than 50 DEG C for controlling high pressure temperature in the kettle, and within about about 30 minutes, logical ammonia terminates.
4), after liquefied ammonia adds, close logical ammonia section door, open hydrogen section door, in autoclave, pass into hydrogen, hydrogen pressure progressively raises, and reaches 8kg/c ㎡, put hydrogen section door into, open hydrogen recycle machine, be warming up to 45 ~ 50 DEG C of reactions, now hydrogen pressure 8 ~ 10kg/c ㎡ in autoclave, hydrogen pressure can decline very soon, then continue logical hydrogen, until in autoclave in hydrogen pressure about 1.5 hours without considerable change, illustrate that Vanillin hydrogenation is complete.
5) after Vanillin reacts completely, high pressure temperature in the kettle is down to less than 40 DEG C, the material that pressure release is taken out in autoclave is dissolved in 150g methyl alcohol, diluted material, filter the Raney's nickel catalyst in removing material, catalyzer completely cuts off air containment and preserves, and can reuse.
By step 5) filtrate be down to room temperature, in filtrate, pass into hydrogen chloride gas to pH=1, filter and collect solids and dries to obtain 3-methoxyl group-4-Hydrobenzylamine hydrochloride finished product 72.8g (0.38mol).
Can obtain 3-methoxyl group in the present embodiment-4-Hydrobenzylamine hydrochloride building-up reactions yield is as calculated 78%.
Embodiment 3:
1) Vanillin of 75g (0.49mol) is dissolved in the anhydrous methanol of 300g for subsequent use in advance.
2) by step 1) in the autoclave of Vanillin solution for standby material suction 1L that dissolved, start to stir, add the Raney's nickel catalyst of 9.4g, add 220g anhydrous methanol again, close all valves of autoclave, first take away most of air by vacuum, then pass into nitrogen and reach 3kg/c ㎡ to autoclave internal pressure, and the sealing of pressure unchanged confirmation autoclave intact after by nitrogen discharge, repetitive operation 2 ~ 3 times, goes out the whole air in autoclave with nitrogen replacement.
3) open autoclave chuck temperature lowering water, control below high pressure temperature in the kettle to 35 DEG C, in autoclave, add 225g (13.2mol) liquefied ammonia, the interpolation speed of liquefied ammonia is less than 50 DEG C for controlling high pressure temperature in the kettle.
4), after liquefied ammonia adds, close logical ammonia section door, open hydrogen section door, in autoclave, pass into hydrogen, hydrogen pressure progressively raises, and reaches 8kg/c ㎡, put hydrogen section door into, open hydrogen recycle machine, be warming up to 45 ~ 50 DEG C of reactions, now hydrogen pressure 8 ~ 10kg/c ㎡ in autoclave, hydrogen pressure can decline very soon, then continue logical hydrogen, until in autoclave in hydrogen pressure about 1.5 hours without considerable change, illustrate that Vanillin hydrogenation is complete.
5) after Vanillin reacts completely, high pressure temperature in the kettle is down to less than 40 DEG C, the material that pressure release is taken out in autoclave is dissolved in 225g methyl alcohol, diluted material, filter the Raney's nickel catalyst in removing material, catalyzer completely cuts off air containment and preserves, and can reuse.
7) by step 5) filtrate be down to room temperature, in filtrate, pass into hydrogen chloride gas to pH=1, filter and collect solids and dries to obtain 3-methoxyl group-4-Hydrobenzylamine hydrochloride finished product 80.3g (0.42mol).
Can obtain 3-methoxyl group in the present embodiment-4-Hydrobenzylamine hydrochloride building-up reactions yield is as calculated 86%.
In sum, the preparation method of this 3-methoxyl group-4-Hydrobenzylamine hydrochloride provided by the invention adopts liquefied ammonia to substitute oxammonium hydrochloride in traditional 3-methoxyl group-4-Hydrobenzylamine hydrochloride synthesis technique, improve product yield, and the raw material adopted is cheap and easy to get, the recyclable recycling of methanol solvate, reduces raw materials cost.
More than exemplifying is only illustrate of the present invention, does not form the restriction to protection scope of the present invention, everyly all belongs within protection scope of the present invention with the same or analogous design of the present invention.
Claims (5)
1. the preparation method of 3-methoxyl group-4-Hydrobenzylamine hydrochloride, it is characterized in that: by Vanillin at solvent methanol, catalyzer Raney's nickel, obtain product 3-methoxyl group-4-Hydrobenzylamine with liquefied ammonia, hydrogen reaction under temperature of reaction 45 ~ 50 DEG C of conditions, then product 3-methoxyl group-4-Hydrobenzylamine is dissolved in methanol solvate and at room temperature obtains 3-methoxyl group-4-Hydrobenzylamine hydrochloride with hcl reaction.
2. the preparation method of 3-methoxyl group-4-Hydrobenzylamine hydrochloride as claimed in claim 1, is characterized in that: this preparation method specifically comprises the steps:
1) be dissolved in anhydrous methanol by Vanillin, the mass ratio of Vanillin and anhydrous methanol is 1:4 ~ 1:2;
2) by step 1) in dissolve Vanillin solution suction autoclave in, stirring adds Raney's nickel catalyst, the Raney's nickel catalyst added and the mass ratio of Vanillin are 1:12 ~ 1:8, go out the air in autoclave with nitrogen replacement;
3) control below high pressure temperature in the kettle to 35 DEG C, in autoclave, add liquefied ammonia, the quality of liquefied ammonia is 1 ~ 3 times of Vanillin;
4) after liquefied ammonia adds, in autoclave, pass into hydrogen, open hydrogen recycle machine, be warming up to 45 ~ 50 DEG C of reactions, until Vanillin reacts completely;
5) high pressure temperature in the kettle is down to less than 40 DEG C, the material that pressure release is taken out in autoclave is dissolved in methyl alcohol, and the mass ratio of methyl alcohol and Vanillin is 2:1 ~ 3:1, crosses and filters Raney's nickel catalyst;
6) by step 5) filtrate be down to room temperature, in filtrate, pass into hydrogen chloride gas to pH=1, filter and collect solids and dries to obtain 3-methoxyl group-4-Hydrobenzylamine hydrochloride finished product.
3. the preparation method of 3-methoxyl group-4-Hydrobenzylamine hydrochloride as claimed in claim 2, is characterized in that: described Raney's nickel catalyst be activated after Raney's nickel.
4. the preparation method of 3-methoxyl group-4-Hydrobenzylamine hydrochloride as claimed in claim 2, it is characterized in that: described step 2) in nitrogen replacement autoclave the detailed process of air for closing all valves of autoclave, first take away most of air by vacuum, then pass into nitrogen and reach 3kg/c ㎡ to autoclave internal pressure, and pressure unchanged after by nitrogen discharge, repetitive operation 2 ~ 3 times.
5. the preparation method of 3-methoxyl group-4-Hydrobenzylamine hydrochloride as claimed in claim 2, is characterized in that: described step 3) in the interpolation speed control high pressure temperature in the kettle of liquefied ammonia be less than 50 DEG C.
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| CN201510494807.XA CN105061231A (en) | 2015-08-12 | 2015-08-12 | Preparation method of 3-methoxy-4-hydroxybenzylamine hydrochloride |
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| CN201510494807.XA CN105061231A (en) | 2015-08-12 | 2015-08-12 | Preparation method of 3-methoxy-4-hydroxybenzylamine hydrochloride |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112608247A (en) * | 2020-12-15 | 2021-04-06 | 遂宁晶安科技有限公司 | Preparation method of capsaicin and capsaicin prepared by using same |
| CN113307759A (en) * | 2021-05-08 | 2021-08-27 | 青岛科技大学 | Cyanine near-infrared fluorescent probe and preparation method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4388250A (en) * | 1982-03-15 | 1983-06-14 | Rhone Poulenc Inc. | Process for the preparation of p-hydroxy-benzyl-nitriles and corresponding amines |
| CN103288665A (en) * | 2013-06-27 | 2013-09-11 | 上海化学试剂研究所有限公司 | Preparation method of capsaicine |
-
2015
- 2015-08-12 CN CN201510494807.XA patent/CN105061231A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4388250A (en) * | 1982-03-15 | 1983-06-14 | Rhone Poulenc Inc. | Process for the preparation of p-hydroxy-benzyl-nitriles and corresponding amines |
| CN103288665A (en) * | 2013-06-27 | 2013-09-11 | 上海化学试剂研究所有限公司 | Preparation method of capsaicine |
Non-Patent Citations (1)
| Title |
|---|
| 彭东明: "4-羟基-3-甲氧基苯甲胺盐酸盐的合成研究", 《精细化工中间体》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112608247A (en) * | 2020-12-15 | 2021-04-06 | 遂宁晶安科技有限公司 | Preparation method of capsaicin and capsaicin prepared by using same |
| CN113307759A (en) * | 2021-05-08 | 2021-08-27 | 青岛科技大学 | Cyanine near-infrared fluorescent probe and preparation method and application thereof |
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