CN101538212A - Method for preparing 4-hydroxy-3-methoxybenzylamine hydrochloride - Google Patents
Method for preparing 4-hydroxy-3-methoxybenzylamine hydrochloride Download PDFInfo
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- CN101538212A CN101538212A CN200910045782A CN200910045782A CN101538212A CN 101538212 A CN101538212 A CN 101538212A CN 200910045782 A CN200910045782 A CN 200910045782A CN 200910045782 A CN200910045782 A CN 200910045782A CN 101538212 A CN101538212 A CN 101538212A
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- hydroxy
- methoxybenzylamine hydrochloride
- methoxybenzene
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- formoxime
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Abstract
The invention discloses a method for preparing 4-hydroxy-3-methoxybenzylamine hydrochloride.. The method comprises the following steps: taking 4-hydroxy-3-methoxyphenyl oxime as the raw material, carrying out the reaction between 4-hydroxy-3-methoxyphenyl oxime and anhydrous ammonium formate as a reducing agent in the presence of a Pd/C catalyst in the methanol reaction solvent; filtering the obtained reaction solution; adding hydrochloric acid to the filtrate for hydrochlorination to obtain the target product of the invention. In the preparation of 4-hydroxy-3-methoxybenzylamine hydrochloride using the method of the invention, the purity thereof can reach over 99%; the yield thereof is higher than 90%; and the melting point thereof is 218 to 219 DEG C. Compared with the prior art, the reaction is carried out under the atmospheric pressure, therefore, the invention has the advantages of safe and convenient operation, stable product quality and high yield, and the method is applicable to industrial production.
Description
Technical field
The present invention relates to the preparation method of a kind of 4-hydroxyl-3-methoxybenzylamine hydrochloride.
Background technology
4-hydroxyl-3-methoxybenzylamine hydrochloride is commonly called as the vanillin food grade,1000.000000ine mesh amine hydrochlorate, it is an important intermediate intending capsaicine N-vanillin food grade,1000.000000ine mesh base-just-pelargonamide, intending capsaicine N-vanillin food grade,1000.000000ine mesh base-just-pelargonamide has the easing pain and diminishing inflammation effect, is widely used in the medicines and health protection field; Having strong and stimulating, lacrimation militarily to can be used as nonlethal weapon uses; Some insects there is preventive and therapeutic effect and is applied to agricultural chemicals; Also be applied to antifouling paint, as the mouse repellent.
The structural formula of 4-hydroxyl-3-methoxybenzylamine hydrochloride is:
In the prior art, the method for preparing 4-hydroxyl-3-methoxybenzylamine hydrochloride mainly contains two kinds: J.Org.Chem.1989,54,3478-3482 has reported that with 4-hydroxy 3-methoxybenzene formaldehyde be raw material, in the presence of ammonium formiate, obtain 4-hydroxyl-3-methoxybenzylamine hydrochloride through reduction amination.Its reaction mechanism is:
Aforesaid method, though 4-hydroxyl-3-methoxybenzylamine hydrochloride content is greater than 98%, but the transformation efficiency of each step process from 4-hydroxy 3-methoxybenzene formaldehyde to synthetic 4-hydroxyl-3-methoxybenzylamine hydrochloride is not high, so that the yield of final product only is 47.5%.
US 2003/0065223 has reported that 4-hydroxy 3-methoxybenzene formoxime and hydrogen at 4bar pressure, carry out hydrogenation reduction under 10 ℃ of conditions, synthetic 4-hydroxyl-3-methoxybenzylamine hydrochloride, and its reaction mechanism is:
Because need the autoclave with acid resistance, erosion resistance, facility investment is big, complex operation, and have suitable danger, industrial prospect is undesirable.
Summary of the invention
Technical problem to be solved by this invention provides the preparation method of a kind of 4-hydroxyl-3-methoxybenzylamine hydrochloride, and is not high with the direct reduction amination method of ammonium formiate yield to overcome in the prior art 4-hydroxy 3-methoxybenzene formaldehyde; Adopt reaction under high pressure, dangerous big, the shortcoming of complex operation.
Technical conceive of the present invention is such: with 4-hydroxy 3-methoxybenzene formoxime is raw material, in the methyl alcohol reaction solvent, the existence of Pd/C catalyzer is descended and anhydrous formic acid ammonium reductive agent reacts, the reacting liquid filtering that obtains, add hydrochloric acid in the filtered liquid and carry out the salt acidifying, promptly obtain target product of the present invention.
Method of the present invention comprises the steps:
4-hydroxy 3-methoxybenzene formoxime, anhydrous formic acid ammonium reductive agent and 5-10wt%Pd/C catalyzer are added in the methanol solvate, at normal pressure, reaction is 2-3 hour under 20-30 ℃ the condition, the reacting liquid filtering that obtains, add 25-30wt% hydrochloric acid in the filtered liquid, collect the target product 4-hydroxyl-3-methoxybenzylamine hydrochloride of separating out.
Reaction formula is as follows:
According to the present invention, the mol ratio of 4-hydroxy 3-methoxybenzene formoxime and anhydrous formic acid ammonium reductive agent is 1: 1.5-3.0, mmol/mmol, the mass ratio of 4-hydroxy 3-methoxybenzene formoxime and Pd/C catalyzer is 4-10: 1, g/g, the weight of 4-hydroxy 3-methoxybenzene formoxime and the volume ratio of methanol solvate are 1: 5-10, g/ml, the weight of 4-hydroxy 3-methoxybenzene formoxime and the volume ratio of hydrochloric acid are 1: 3-6, g/ml.
4-hydroxyl-3-methoxybenzylamine hydrochloride the purity that obtains with preparation method of the present invention reaches more than 99%, and productive rate is greater than 90%, and fusing point is 219-220 ℃, consistent with literature value (literature value: 218～219 ℃).
Raw material 4-hydroxy 3-methoxybenzene formoxime used in the present invention can be according to J.Org.Chem.53 (5), and 1988, the 1064-1071 reported method prepares, and the present invention repeats no more.The present invention is reflected under the normal pressure and carries out compared with prior art, simple and safe operation, and constant product quality, the productive rate height is suitable for suitability for industrialized production.
Embodiment
The invention will be further described below by embodiment, but embodiment does not limit protection scope of the present invention.
Embodiment 1
Having heating, stir, add 150ml methyl alcohol in the reactor of thermometer condenser respectively, 4-hydroxy 3-methoxybenzene formoxime 16.7g (100mmol), anhydrous formic acid ammonium 14.5g (230mmol), the adding concentration expressed in percentage by weight is 5% Pd/C catalyzer 4.0g under stirring, temperature of reaction is controlled at 20-30 ℃, reacted 3 hours, the reacting liquid filtering that obtains, filter residue is the Pd/C catalyzer, recycle after concentrating recovery, the adding concentration expressed in percentage by weight is 30% hydrochloric acid 100ml in the filtrate, separates out white crystal, filter out crystal, drying obtains target product 4-hydroxyl-3-methoxybenzylamine hydrochloride 17.1g, productive rate 90.2%, purity is 99.5% (HPLC), and fusing point is 219.2～220.0 ℃.
Embodiment 2
Having heating, stir, add 100ml methyl alcohol in the reactor of thermometer condenser respectively, 4-hydroxy 3-methoxybenzene formoxime 16.7g (100mmol), anhydrous formic acid ammonium 12.6g (200mmol), stirring down, the adding concentration expressed in percentage by weight is 10%Pd/C catalyzer 2.0g, temperature of reaction is controlled at 20-30 ℃, reacted 2 hours, the reacting liquid filtering that obtains, filter residue is the Pd/C catalyzer, recycle after concentrating recovery, the adding concentration expressed in percentage by weight is 30% hydrochloric acid 50ml in the filtrate, separates out white crystal, filter out crystal, drying obtains target product 4-hydroxyl-3-methoxybenzylamine hydrochloride 17.4g, productive rate 91.8%, purity is 99.6% (HPLC), and fusing point is 219.4～220.2 ℃.
Claims (5)
1. the preparation method of 4-hydroxyl-3-methoxybenzylamine hydrochloride is characterized in that, comprises the steps:
4-hydroxy 3-methoxybenzene formoxime, anhydrous formic acid ammonium reductive agent and 5-10wt%Pd/C catalyzer are added in the methanol solvate, reaction is 2-3 hour under the condition of normal pressure, 20-30 ℃, the reacting liquid filtering that obtains, add 25-30wt% hydrochloric acid in the filtered liquid, collect the target product 4-hydroxyl-3-methoxybenzylamine hydrochloride of separating out.
2. the preparation method of a kind of 4-hydroxyl according to claim 1-3-methoxybenzylamine hydrochloride is characterized in that the mol ratio of said 4-hydroxy 3-methoxybenzene formoxime and anhydrous formic acid ammonium reductive agent is 1: 1.5-3.0, mmol/mmol.
3. the preparation method of a kind of 4-hydroxyl according to claim 1-3-methoxybenzylamine hydrochloride is characterized in that the mass ratio of said 4-hydroxy 3-methoxybenzene formoxime and Pd/C catalyzer is 4-10: 1, and g/g.
4. the preparation method of a kind of 4-hydroxyl according to claim 1-3-methoxybenzylamine hydrochloride is characterized in that the weight of said 4-hydroxy 3-methoxybenzene formoxime and the volume ratio of methanol solvate are 1: 5-10, g/ml.
5. the preparation method of a kind of 4-hydroxyl according to claim 1-3-methoxybenzylamine hydrochloride is characterized in that the weight of said 4-hydroxy 3-methoxybenzene formoxime and the volume ratio of hydrochloric acid are 1: 3-6, g/ml.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910045782A CN101538212A (en) | 2009-02-05 | 2009-02-05 | Method for preparing 4-hydroxy-3-methoxybenzylamine hydrochloride |
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| CN200910045782A CN101538212A (en) | 2009-02-05 | 2009-02-05 | Method for preparing 4-hydroxy-3-methoxybenzylamine hydrochloride |
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| CN101538212A true CN101538212A (en) | 2009-09-23 |
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| CN200910045782A Pending CN101538212A (en) | 2009-02-05 | 2009-02-05 | Method for preparing 4-hydroxy-3-methoxybenzylamine hydrochloride |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102417462A (en) * | 2011-08-30 | 2012-04-18 | 上海华谊（集团）公司 | Preparation method of 4-hydroxy-3-ethoxybenzylamine hydrochloride |
| CN105294449A (en) * | 2014-06-16 | 2016-02-03 | 连云港手性化学有限公司 | Preparation method for (R)-(+)-1-(1-naphthyl)ethylamine and (S)-(-)-1-(1-naphthyl)ethylamine |
| CN106366004A (en) * | 2016-08-08 | 2017-02-01 | 河南省化工研究所有限责任公司 | Preparation method for vanillylamine hydrochloride |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6054342A (en) * | 1983-09-05 | 1985-03-28 | Agency Of Ind Science & Technol | Preparation of vanillylamine hydrochloride |
-
2009
- 2009-02-05 CN CN200910045782A patent/CN101538212A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6054342A (en) * | 1983-09-05 | 1985-03-28 | Agency Of Ind Science & Technol | Preparation of vanillylamine hydrochloride |
Non-Patent Citations (2)
| Title |
|---|
| PETER M. GANNETT ET AL.: "The Capsaicinoids: Their Separation, Synthesis, and Mutagenicity", 《J. ORG. CHEM.》 * |
| 尤启冬 等: "催化氢转移还原肟成胺", 《中国医药工业杂志》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102417462A (en) * | 2011-08-30 | 2012-04-18 | 上海华谊（集团）公司 | Preparation method of 4-hydroxy-3-ethoxybenzylamine hydrochloride |
| CN105294449A (en) * | 2014-06-16 | 2016-02-03 | 连云港手性化学有限公司 | Preparation method for (R)-(+)-1-(1-naphthyl)ethylamine and (S)-(-)-1-(1-naphthyl)ethylamine |
| CN105294449B (en) * | 2014-06-16 | 2017-02-08 | 连云港手性化学有限公司 | Preparation method for (R)-(+)-1-(1-naphthyl)ethylamine and (S)-(-)-1-(1-naphthyl)ethylamine |
| CN106366004A (en) * | 2016-08-08 | 2017-02-01 | 河南省化工研究所有限责任公司 | Preparation method for vanillylamine hydrochloride |
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Application publication date: 20090923 |