CN103214381A - Method for preparing 2-hydroxyl-2-(4-methoxylphenyl) ethylamine hydrochloride - Google Patents
Method for preparing 2-hydroxyl-2-(4-methoxylphenyl) ethylamine hydrochloride Download PDFInfo
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- CN103214381A CN103214381A CN2013101759537A CN201310175953A CN103214381A CN 103214381 A CN103214381 A CN 103214381A CN 2013101759537 A CN2013101759537 A CN 2013101759537A CN 201310175953 A CN201310175953 A CN 201310175953A CN 103214381 A CN103214381 A CN 103214381A
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Abstract
The invention relates to a method for preparing 2-hydroxyl-2-(4-methoxylphenyl) ethylamine hydrochloride. The method comprises the following steps of: based on benzaldehyde as a raw material, performing acylation reaction with glycinonitrile hydrochloride in the presence of anhydrous aluminium chloride, then hydrolyzing to obtain carbonyl compounds, and then performing catalytic hydrogenation to prepare 2-hydroxyl-2-(4-methoxylphenyl) ethylamine hydrochloride. The method is mainly characterized in that in the reaction, dichloromethane is used as a solvent, the molar ratio of benzaldehyde to glycinonitrile hydrochloride is 1: 1, and the temperature and time during the reaction process are controlled, thus increasing the yield of products. The method disclosed by the invention further has the advantages of being easy in obtaining of raw materials, cheap in the raw materials, capable of recycling the solvent and thus reducing cost, friendly in condition environment, simple in steps, easy to operate, short in synthesis route, and the like.
Description
Technical field
The present invention relates to the method for a kind of 2-of preparation hydroxyl-2-(4-p-methoxy-phenyl) ethylamine hydrochloride.The specific requirement protection is that raw material carries out the acylations reflection with the aminoacetonitriles hydrochloride with the methyl-phenoxide in the presence of aluminum trichloride (anhydrous), and hydrolysis gets carbonyl compound then, and shortening makes again.
Background technology
As far back as 20 beginnings of the century, scientist finds that by human dissection when people's mood changed, the diencephalon bottom in people's brain can a series of compounds of secretion.This class chemical molecular has phenylethylamine, endorphin etc., and scientist is referred to as " mood hormone ".Recently scientist finds, not only the people knows from experience syntheticly automatically, discharges phenylethylamine, and in many food profuse phenylethylamine is arranged also, and is for example chocolate or contain in the chocolate food, especially the more dark chocolate of cocoa content.It also has some special abilities, is called by scientist's image " chemical molecular of love ".
Phenylethylamine can absorb carbon dioxide in air, becomes corresponding carbonate.Also do not solidify (fusing point-65 ℃) with chilled brine cooling, this compounds is by stimulating gland picric acid cyclase system and other second messengers, thereby produces various physiological effects, its hydrochloride is a plate crystal, 217 ℃ of fusing points (from alcohol, separating out), soluble in water, be dissolved in alcohol, but be insoluble to ether.Phenylethylamine is organic synthesis and medical, the important intermediate of dyestuffs industries, wherein the development research of the phenylethylamine that replaces of hydroxyl, alkoxyl group enjoys vast chemical research person's concern, its pharmaceutically be mainly used in synthetic energizer, god goes into to feel exciting agent, falls medicines such as appetite agent, bronchodilator, thymoleptic.With phenol is the synthetic octopamine of raw material, it can be used as neurotransmitter, neurohormone or neuroregulator in the invertebrates nervous tissue, to the getting food, migrate and physiological process such as breeding plays regulating effect of insect, also can strengthen diseases such as human body metabolic function and treatment neurasthenia.With methyl-phenoxide and vinyl cyanide is that raw material synthetic Uteramin has effects such as rising blood pressure and excited uterus, can be used as the medicine of stimulant, treatment migraine and diagnosis pheochromocytoma, and its hydrochloride is the intermediate of preparation hypotensor bezafibrate.
Phenylethylamine can be replaced by other groups on phenyl ring, side chain and amino, thus synthetic more phenylethylamine compounds.Therefore; this technology on the phenylethylamine basis is that raw material carries out the acylations reflection with the aminoacetonitriles hydrochloride with the methyl-phenoxide in the presence of aluminum trichloride (anhydrous); hydrolysis gets carbonyl compound then, and shortening makes the method for 2-hydroxyl-2-(4-p-methoxy-phenyl) ethylamine hydrochloride again.And the present invention also has raw material and easily obtains, and synthetic route is short, and is simple to operate, and conditions environmental is friendly, and the reaction times is shorter, the recyclable utilization of solvent advantage such as reduce cost.
Summary of the invention
Core technology problem to be solved by this invention provides the method for a kind of 2-of preparation hydroxyl-2-(4-p-methoxy-phenyl) ethylamine hydrochloride, sets up and innovates synthetic route efficiently.
The technical scheme that the present invention solves its technical problem employing is: the method for a kind of 2-of preparation hydroxyl-2-(4-p-methoxy-phenyl) ethylamine hydrochloride may further comprise the steps:
(1) preparation of 2-oxygen-2-(4-p-methoxy-phenyl) ethylamine hydrochloride
With anhydrous AlCl
3The aminoacetonitriles hydrochloride, methyl-phenoxide joins methylene dichloride, Nitromethane 99Min., in the organic solvents such as chlorobenzene, logical nitrogen replacement, stirring heating maintains the temperature between 35～45 degrees centigrade, react completely up to detecting methyl-phenoxide, reduce to room temperature then, standing demix is poured out the most of methylene dichloride in upper strata, Nitromethane 99Min., organic solvents such as chlorobenzene, lower floor's imines is under vigorous stirring and water-bath cooling, slowly add frozen water, after adding, cooling, suction filtration, acetone rinsing, drying gets the faint yellow solid crude product, in case of necessity can be in water with dissolving crude product, logical HCl gas then has faint yellow or greenish orange red crystallization to separate out, and purity is 99%.
(2) preparation of 2-hydroxyl-2-(4-p-methoxy-phenyl) ethylamine hydrochloride
At first be the preparation of the active Raney nickel catalyzator of W-7: sodium hydroxide and distilled water input are equipped with in the flask of stirring and thermometer, stirring makes its dissolving, cool off slightly, under the vigorous stirring, add the Ni-Al alloy one by one, regulate alloy adding speed and bath temperature a bottle interior liquid temperature is remained on about 50 degrees centigrade.After adding finishes, slowly stir down, in (50 ± 2) ℃ insulation 50min, remove the top clear liquor, being washed till pH with distilled water is 7～8, and 2-oxygen-2-that (1) is made (4-p-methoxy-phenyl) ethylamine hydrochloride is dissolved in the distilled water then, add the active Raney nickel catalyzator of freshly prepd W-7, N
2Emptying feeds H
2, mechanical stirring keeps 45 ℃ of temperature, and reaction 8～10h is until no gas absorption, reduce to room temperature, filtering recovering catalyst obtains pistac solution, and dense solid carbon dioxide branch gets the off-white color solid, with ethanol or butanone recrystallization, get white solid, yield 86%, purity 99%.
Further, be raw material with methyl-phenoxide, aminoacetonitriles hydrochloride etc. in the step (1).
Further, the mol ratio of methyl-phenoxide and aminoacetonitriles hydrochloride is 1: 1 in the step (1).
Further, the organic solvent of selecting for use in the step (1) is that the methylene dichloride effect is best.
Further, maintain the temperature at 40 ℃ of following stirring reaction 5h in the step (1).
Further, N in the step (2)
2Emptying, logical H
2Mechanical stirring is incubated 45 ℃, reaction 9h.
Further, get the off-white color solid in the step (2), the suitableeest with ethyl alcohol recrystallization.
The present invention is the method for a kind of 2-of preparation hydroxyl-2-(4-p-methoxy-phenyl) ethylamine hydrochloride, have raw material be easy to get, cheap, the recyclable utilization of solvent, the conditions environmental close friend, step is simple, and is easy to operate, advantages such as synthetic route is short, product yield 86%, high-efficient liquid phase color spectral purity 99.9%.
Description of drawings
Accompanying drawing is the building-up reactions route of 2-hydroxyl-2-(4-p-methoxy-phenyl) ethylamine hydrochloride.
Embodiment
The invention will be further described below in conjunction with embodiment.
Embodiment 1
May further comprise the steps:
(1) preparation of 2-oxygen-2-(4-p-methoxy-phenyl) ethylamine hydrochloride
With anhydrous 20gAlCl
3, 7g aminoacetonitriles hydrochloride, 8ml methyl-phenoxide join logical nitrogen replacement in the 70ml methylene dichloride, stirring heating maintains the temperature at about 40 ℃, reacts completely up to detecting methyl-phenoxide, approximately 5h.Reduce to room temperature then, standing demix is poured out the most of ethylene dichloride in upper strata, lower floor's imines slowly adds frozen water under vigorous stirring and water-bath cooling, finish, cooling, suction filtration, acetone is washed, drying, faint yellow solid crude product 10.6g, crude product yield 76%, in case of necessity can be in water with dissolving crude product, logical HCl gas has faint yellow or the incarnadine crystallization is separated out, purity 99%.
(2) preparation of 2-hydroxyl-2-(4 p-methoxy-phenyl) ethylamine hydrochloride
At first be the preparation of the active Raney nickel catalyzator of W-7: 20g sodium hydroxide and 80ml distilled water input are equipped with in the flask of stirring and thermometer, stirring makes its dissolving, cool off slightly, under the vigorous stirring, add the 16gNi-Al alloy one by one, regulate alloy adding speed and bath temperature a bottle interior liquid temperature is remained on about 50 degrees centigrade.After adding finishes, slowly stir down, in (50 ± 2) ℃ insulation 50min, remove the top clear liquor, being washed till pH with distilled water is 7～8.
19g2-oxygen-2-(4-p-methoxy-phenyl) ethylamine hydrochloride is dissolved in the 150ml distilled water, adds the active Raney nickel catalyzator of freshly prepd W-7, N
2Emptying, logical H
2, mechanical stirring is incubated 45 ℃, reacts 9h, until no gas absorption, reduces to room temperature, and filtering recovering catalyst obtains pistac solution, concentrates moisture to doing, and gets the off-white color solid, uses ethyl alcohol recrystallization, gets white solid 16.3g, yield 86%, purity 99%.
Embodiment 2
May further comprise the steps:
(1) preparation of 2-oxygen-2-(4-p-methoxy-phenyl) ethylamine hydrochloride
With anhydrous 20gAlCl
3, 7g aminoacetonitriles hydrochloride, 8ml methyl-phenoxide join logical nitrogen replacement in the 70ml Nitromethane 99Min., stirring heating maintains the temperature at about 40 ℃, reacts completely up to detecting methyl-phenoxide, approximately 5h.Reduce to room temperature then, standing demix is poured out the most of Nitromethane 99Min. in upper strata, lower floor's imines slowly adds frozen water under vigorous stirring and water-bath cooling, finish, cooling, suction filtration, acetone is washed, drying, faint yellow solid crude product 9.7g, crude product yield 70%, in case of necessity can be in water with dissolving crude product, logical HCl gas has faint yellow or the incarnadine crystallization is separated out, purity 99%.
(2) preparation of 2-hydroxyl-2-(4 p-methoxy-phenyl) ethylamine hydrochloride
At first be the preparation of the active Raney nickel catalyzator of W-7: 20g sodium hydroxide and 80ml distilled water input are equipped with in the flask of stirring and thermometer, stirring makes its dissolving, cool off slightly, under the vigorous stirring, add the 16gNi-Al alloy one by one, regulate alloy adding speed and bath temperature a bottle interior liquid temperature is remained on about 50 degrees centigrade.After adding finishes, slowly stir down, in (50 ± 2) ℃ insulation 50min, remove the top clear liquor, being washed till pH with distilled water is 7～8.
19g2-oxygen-2-(4-p-methoxy-phenyl) ethylamine hydrochloride is dissolved in the 150ml distilled water, adds the active Raney nickel catalyzator of freshly prepd W-7, N
2Emptying, logical H
2, mechanical stirring is incubated 45 ℃, reacts 9h, until no gas absorption, reduces to room temperature, and filtering recovering catalyst obtains pistac solution, concentrates moisture to doing, and gets the off-white color solid, uses ethyl alcohol recrystallization, gets white solid 16.3g, yield 86%, purity 99%.
Embodiment 3
May further comprise the steps:
(1) preparation of 2-oxygen-2-(4-p-methoxy-phenyl) ethylamine hydrochloride
With anhydrous 20gAlCl
3, 7g aminoacetonitriles hydrochloride, 8ml methyl-phenoxide join logical nitrogen replacement in the 70ml chlorobenzene, stirring heating maintains the temperature at about 40 ℃, reacts completely up to detecting methyl-phenoxide, approximately 5h.Reduce to room temperature then, standing demix is poured out the most of chlorobenzene in upper strata, lower floor's imines slowly adds frozen water under vigorous stirring and water-bath cooling, finish, cooling, suction filtration, acetone is washed, drying, faint yellow solid crude product 7g, crude product yield 50%, in case of necessity can be in water with dissolving crude product, logical HCl gas has faint yellow or the incarnadine crystallization is separated out, purity 99%.
(2) preparation of 2-hydroxyl-2-(4 p-methoxy-phenyl) ethylamine hydrochloride
At first be the preparation of the active Raney nickel catalyzator of W-7: 20g sodium hydroxide and 80ml distilled water input are equipped with in the flask of stirring and thermometer, stirring makes its dissolving, cool off slightly, under the vigorous stirring, add the 16gNi-Al alloy one by one, regulate alloy adding speed and bath temperature a bottle interior liquid temperature is remained on about 50 degrees centigrade.After adding finishes, slowly stir down, in (50 ± 2) ℃ insulation 50min, remove the top clear liquor, being washed till pH with distilled water is 7～8.
19g2-oxygen-2-(4-p-methoxy-phenyl) ethylamine hydrochloride is dissolved in the 150ml distilled water, adds the active Raney nickel catalyzator of freshly prepd W-7, N
2Emptying, logical H
2, mechanical stirring is incubated 45 ℃, reacts 9h, until no gas absorption, reduces to room temperature, and filtering recovering catalyst obtains pistac solution, concentrates moisture to doing, and gets the off-white color solid, uses ethyl alcohol recrystallization, gets white solid 16.3g, yield 86%, purity 99%.
Claims (7)
1. the method for system 2-hydroxyl-2-(4-p-methoxy-phenyl) ethylamine hydrochloride; it is characterized in that; with the methyl-phenoxide is raw material; under the condition that aluminum trichloride (anhydrous) exists, carry out the F-C acylation reaction with the aminoacetonitriles hydrochloride; hydrolysis obtains carbonyl compound then; make with Raney nickel shortening, its concrete steps are as follows again:
(1) preparation of 2-oxygen-2-(4-p-methoxy-phenyl) ethylamine hydrochloride is with anhydrous AlCl
3The aminoacetonitriles hydrochloride, methyl-phenoxide joins methylene dichloride, Nitromethane 99Min., in the organic solvents such as chlorobenzene, logical nitrogen replacement, stirring heating maintains the temperature between 35～45 degrees centigrade, react completely up to detecting methyl-phenoxide, reduce to room temperature then, standing demix is poured out the most of methylene dichloride in upper strata, Nitromethane 99Min., organic solvents such as chlorobenzene, lower floor's imines is under vigorous stirring and water-bath cooling, slowly add frozen water, after adding, cooling, suction filtration, acetone rinsing, drying gets the faint yellow solid crude product, in case of necessity can be in water with dissolving crude product, logical HCl gas then has faint yellow or greenish orange red crystallization to separate out, and purity is 99%;
(2) preparation of 2-hydroxyl-2-(4 p-methoxy-phenyl) ethylamine hydrochloride, at first be the preparation of the active Raney nickel catalyzator of W-7: sodium hydroxide and distilled water input are equipped with in the flask of stirring and thermometer, stirring makes its dissolving, cool off slightly, under the vigorous stirring, add the Ni-Al alloy one by one, regulating alloy adding speed and bath temperature remains on about 50 degrees centigrade a bottle interior liquid temperature, after adding finishes, slowly stir down, in (50 ± 2) ℃ insulation 50min, remove the top clear liquor, being washed till pH with distilled water is 7～8, and 2-oxygen-2-(4-p-methoxy-phenyl) ethylamine hydrochloride that (1) is made is dissolved in the distilled water, add the active Raney nickel catalyzator of freshly prepd W-7, N
2Emptying feeds H
2, mechanical stirring keeps 45 ℃ of temperature, and reaction 8～10h is until no gas absorption, reduce to room temperature, filtering recovering catalyst obtains pistac solution, and dense solid carbon dioxide branch gets the off-white color solid, with ethanol or butanone recrystallization, get white solid, yield 86%, purity 99%.
2. the method for preparing 2-hydroxyl-2-(4-p-methoxy-phenyl) ethylamine hydrochloride according to claim 1 is characterized in that in the step (1) with methyl-phenoxide, aminoacetonitriles hydrochloride etc. being raw material.
3. the method for preparing 2-hydroxyl-2-(4-p-methoxy-phenyl) ethylamine hydrochloride according to claim 1 is characterized in that the mol ratio of middle methyl-phenoxide of step (1) and aminoacetonitriles hydrochloride is 1: 1.
4. the method for preparing 2-hydroxyl-2-(4-p-methoxy-phenyl) ethylamine hydrochloride according to claim 1 is characterized in that the organic solvent of selecting for use in the step (1) is that the methylene dichloride effect is best.
5. the method for preparing 2-hydroxyl-2-(4-p-methoxy-phenyl) ethylamine hydrochloride according to claim 1 is characterized in that maintaining the temperature in the step (1) 40 ℃ of following stirring reaction 5h.
6. the method for preparing 2-hydroxyl-2-(4-p-methoxy-phenyl) ethylamine hydrochloride according to claim 1 is characterized in that N in the step (2)
2Emptying, logical H
2Mechanical stirring is incubated 45 ℃, reaction 9h.
7. the method for preparing 2-hydroxyl-2-(4-p-methoxy-phenyl) ethylamine hydrochloride according to claim 1 is characterized in that getting the off-white color solid in the step (2), and is the suitableeest with ethyl alcohol recrystallization.
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| CN2013101759537A CN103214381A (en) | 2013-05-14 | 2013-05-14 | Method for preparing 2-hydroxyl-2-(4-methoxylphenyl) ethylamine hydrochloride |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112986423A (en) * | 2021-02-07 | 2021-06-18 | 山东京博生物科技有限公司 | Content analysis method and application of aminoacetonitrile hydrochloride |
Citations (3)
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| US3886166A (en) * | 1972-12-22 | 1975-05-27 | Siphar Sa | Method for the synthesis of ({35 )-glaziovine |
| CN102040529A (en) * | 2010-11-09 | 2011-05-04 | 杭州福斯特药业有限公司 | Method for synthesizing synephrine hydrochloride |
| CN102381989A (en) * | 2010-08-30 | 2012-03-21 | 苏州洪瑞医药科技有限公司 | Chemical synthetic method for synephrine hydrochloride |
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2013
- 2013-05-14 CN CN2013101759537A patent/CN103214381A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3886166A (en) * | 1972-12-22 | 1975-05-27 | Siphar Sa | Method for the synthesis of ({35 )-glaziovine |
| CN102381989A (en) * | 2010-08-30 | 2012-03-21 | 苏州洪瑞医药科技有限公司 | Chemical synthetic method for synephrine hydrochloride |
| CN102040529A (en) * | 2010-11-09 | 2011-05-04 | 杭州福斯特药业有限公司 | Method for synthesizing synephrine hydrochloride |
Non-Patent Citations (3)
| Title |
|---|
| WILLIAM J. KELLER等: "Selectivity of 4-MethoxyphenethylamineDerivatives as Inhibitors of Monoamine Oxidase", 《JOURNAL OF PHARMACEUTICAL SCIENCES》 * |
| 余小兵等: "Raney-Ni催化剂的研究进展", 《化学通报（网络版）》 * |
| 黄枢等: "《有机合成试剂制备手册（第二版）》", 31 March 2005, 科学出版社 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112986423A (en) * | 2021-02-07 | 2021-06-18 | 山东京博生物科技有限公司 | Content analysis method and application of aminoacetonitrile hydrochloride |
| CN112986423B (en) * | 2021-02-07 | 2022-09-23 | 山东京博生物科技有限公司 | Content analysis method of aminoacetonitrile hydrochloride and application thereof |
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Application publication date: 20130724 |