CN101311162B - Method for preparing 2,5-dimethoxy phenylethylamine - Google Patents
Method for preparing 2,5-dimethoxy phenylethylamine Download PDFInfo
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- CN101311162B CN101311162B CN2008100616130A CN200810061613A CN101311162B CN 101311162 B CN101311162 B CN 101311162B CN 2008100616130 A CN2008100616130 A CN 2008100616130A CN 200810061613 A CN200810061613 A CN 200810061613A CN 101311162 B CN101311162 B CN 101311162B
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Abstract
The invention relates to a preparation method for 2, 5-dimethoxyphenethylamine which is an important pharmaceutical intermediate; the method includes the following steps in sequence: 1, 4-dimethoxy benzene and chloracetyl chloride carry out Friedel-Crafts reaction to obtain Alpha-chlorine-2, 5-dimethoxy acetophenone which then reacts with methenamine to obtain Alpha-amino-2, 5-dimethoxy acetophenone, and finally the Alpha-amino-2, 5-dimethoxy acetophenone reacts with a reducer to obtain the product, that is, the 2, 5-dimethoxyphenethylamine. The invention discloses a brand new synthetic route, the used raw materials are all derived from the market and have rich and extensive sources with low price; moreover, the reaction condition is mild, the technique is simple, all steps are routine operation, thus overcoming the disadvantages of troublesome operation steps, difficult post treatment, expensive reducer, and so on in the traditional preparation method.
Description
Technical field
The present invention relates to a kind of preparation method of important medicine intermediate, relate in particular to a kind of 2, the preparation method of 5-dimethoxy-phenylethylamine.
Background technology
Fragrance ethamine (ArCH
2CH
2NH
2) be the important intermediate of organic synthesis and medicine industry.Have the psychosis activity of plan and antineoplastic action as 4-anisole ethamine; Uteramin (having another name called tyrasamine), be a kind of compound of from ergotine and rotten animal tissues, separating at first, because this compound has the pharmacological action of rising blood pressure, people are synthesized it again with the artificial method, mainly be at present to use as biochemical reagents, organic chemical industry and medicine intermediate; 2, the 4-dimethoxy-phenylethylamine has spasmolysis; 3, the stenocardia that 4-dimethoxy-N-Methylphenethylamine is used for the treatment of and prevents to cause owing to coronary vasospasm.The intermediate of treatment arrhythmia and hypertensive medicine verapamil (verapamil); And 2, the 5-dimethoxy-phenylethylamine is the main raw material of synthetic serotonine (5-HT) compounds.At present, this series products at home and abroad market requirement is big and show a rising trend, and is expensive.
In present industrial production and experimental study.Main employing 2, the reflux condensation in Glacial acetic acid of 5-dimethoxy benzaldehyde and Nitromethane 99Min. obtains beta-nitrostyrene, again through reduction preparation 2,5-dimethoxy-phenylethylamine.In reduction reaction, reductive agent generally adopts diborane, lithium aluminum hydride, and reductive agent costs an arm and a leg, and makes cost higher, and reaction requires anhydrous and oxygen-free, and solvent load is big, reclaims trouble, and environmental pollution is serious.
Summary of the invention
The present invention is in order to solve the problems of the technologies described above, provide a kind of reaction conditions gentleness, technology and equipment simple, be convenient to operate, raw material sources are extensive and harmless environment a kind of 2, the preparation method of 5-dimethoxy-phenylethylamine.
Above-mentioned technical problem of the present invention is mainly solved by following technical proposals: of the present invention 2, the 5-dimethoxy-phenylethylamine is with formula (I) expression, and 2, the preparation method of 5-dimethoxy-phenylethylamine obtains according to following steps:
A. α-chloro-2, the preparation of 5-dimethoxy-acetophenone:
In reactor, add 1,1 part of 4-dimethoxy benzene, 1.0～1.5 parts of chloroacetyl chlorides, 6～9 parts of 1.1 parts of lewis acid catalysts and organic solvents, stir room temperature reaction, pour in 2～3 parts of the concentrated hydrochloric acids organic solvent extraction separatory after reaction finishes into, dry back removal of solvent under reduced pressure obtains the α-chloro-2 with formula (II) expression, 5-dimethoxy-acetophenone;
B. alpha-amino group-2, the preparation of 5-dimethoxy-acetophenone:
In reactor, add α-chloro-2,1 part of 5-dimethoxy-acetophenone, 1～5 part of urotropine, concentration is 8～12 parts of 95% ethanol, back flow reaction to a large amount of solids generate under agitation condition, stirring reaction finishes after-filtration and collects solid, then solid is dissolved in 5～15 parts of concentrated hydrochloric acids and the ethanol, back flow reaction, it is that 5% aqueous sodium hydroxide solution transfers to alkalescence with concentration that reaction finishes the cooling back, uses the ethyl acetate extraction separatory then, removal of solvent under reduced pressure after the ethyl acetate layer drying, obtain alpha-amino group-2, the 5-dimethoxy-acetophenone with formula (III) expression;
C.2, the preparation of 5-dimethoxy-phenylethylamine:
In reactor, add alpha-amino group-2,1 part of 5-dimethoxy-acetophenone, 1.5～2.5 parts in potassium hydroxide, 2～8 parts of 10～15 parts of organic solvents and hydrazine hydrates, stirring and refluxing reaction, reaction finish postcooling to room temperature and pour in the frozen water, the ethyl acetate extraction separatory, removal of solvent under reduced pressure after the ethyl acetate layer drying, underpressure distillation obtains 2, the 5-dimethoxy-phenylethylamine.
As preferably, used lewis acid catalyst is any one in aluminum trichloride (anhydrous) or the boron trifluoride ether solution in the described A step; Organic solvent is the alkyl chloride kind solvent, is methylene dichloride or 1,2-ethylene dichloride or vinyl trichloride; The consumption of chloroacetyl chloride is 1,1.1 times of the consumption of 4-dimethoxy benzene.
As preferably, the consumption of urotropine is α-chloro-2 in the described B step, 3 times of 5-dimethoxy-acetophenone, and the reaction times is 12～24 hours; The consumption of concentrated hydrochloric acid is α-chloro-2,10 times of 5-dimethoxy-acetophenone, and reflux time is 12～36 hours.
As preferably, used organic solvent is ethylene glycol or glycol ether in the described C step, and the consumption of hydrazine hydrate is an alpha-amino group-2,6 times of 5-dimethoxy-acetophenone, and the reaction times is 12～24 hours.
The invention has the beneficial effects as follows:
1. adopt brand-new synthetic route, the volume production of this product is had important theory directive significance and actually operating meaning.
The poly-raw material that adopts of each step be commercially available, wide material sources, in liberal supply and low price.
3. gentleness and technology are simple relatively for reaction conditions, and each step reaction is routine operation, is easy to control, need not complex apparatus, and less to the pollution of environment.
Embodiment
Below by embodiment, and in conjunction with the accompanying drawings, technical scheme of the present invention is described in further detail.
Embodiment 1: present embodiment a kind of 2, the preparation method of 5-dimethoxy-phenylethylamine, carry out according to following steps:
A. α-chloro-2, the preparation of 5-dimethoxy-acetophenone
Reflux condensing tube is being housed, constant pressure funnel, add 1 in the 500ml three-necked bottle of thermometer and magnetic stirring apparatus, 4-dimethoxy benzene (60g, 0.44mol), methylene dichloride (240ml), after the stirring and dissolving, add aluminum trichloride (anhydrous) (64g, 0.48mol), finish the back and continued stirring at room 5 minutes, drip then chloroacetyl chloride (40ml, 0.5mol) and the mixed solution of methylene dichloride (40ml), dropwised in about 90 minutes, continued stirring at room then 4 hours, and poured into and continue in the 130ml concentrated hydrochloric acid that contains trash ice to stir 30 minutes, mixture extracts with methylene dichloride (100ml * 3), separatory, the dichloromethane layer anhydrous sodium sulfate drying obtains yellow solid after the removal of solvent under reduced pressure, be crude product.Crude product recrystallization in methyl alcohol obtains α-chloro-2,5-dimethoxy-acetophenone (59.0g), yield 64.0%, 89-91 ℃ of product fusing point (decomposition).1H?NMR(CDCl3，500MHz)δ：3.80(3H，s)，3.90(3H，s)，4.80(2H，s)，6.9(1H，J＝9.2Hz)，7.10(1H，m-dd，J＝3.2，9.2Hz)，7.40(1H，m-d，J＝3.2Hz)。
B. alpha-amino group-2, the preparation of 5-dimethoxy-acetophenone
In being housed, the 500ml three-necked bottle of reflux condensing tube, thermometer and magnetic stirring apparatus adds α-chloro-2,5-dimethoxy-acetophenone (21.4g, 0.1mol) and concentration be 95% ethanol (200ml), add urotropine (42g after the stirring and dissolving, 0.3mol), stirring at room reaction 18 hours, reaction mixture is separated out a large amount of solids, and the stopped reaction after-filtration is collected solid.
Reflux condensing tube is being housed, add the above-mentioned solid that obtains in the 500ml three-necked bottle of thermometer and magnetic stirring apparatus, be dissolved in concentrated hydrochloric acid (100ml) and the ethanol (100ml), reflux 24 hours, reaction end back slow adding concentration under the ice-water bath cooling conditions is 5% aqueous sodium hydroxide solution, regulating mixture pH is alkalescence, mixture extracts with ethyl acetate (100ml * 3) then, separatory, the ethyl acetate layer anhydrous sodium sulfate drying, obtain alpha-amino group-2 after the removal of solvent under reduced pressure, 5-dimethoxy-acetophenone crude product (15.0g), content is greater than 96%, yield 76.9% need not be further purified and can be directly used in next step reaction.
C.2, the preparation of 5-dimethoxy-phenylethylamine
The reflux water-dividing device is being housed, add alpha-amino group-2 in the 1000ml three-necked bottle of thermometer and magnetic stirring apparatus, 5-dimethoxy-acetophenone (19.5g, 0.1mol), potassium hydroxide (33.6g, 0.6mol), glycol ether (240ml) and concentration are 80% hydrazine hydrate (38ml, about 0.6mol), stirring and refluxing is divided the water reaction, until the water of telling above theoretical amount, continue again to reflux 2 hours, have about 18 hours altogether, reaction finishes, reaction mixture is poured in the frozen water after being cooled to room temperature, and mixed solution extracts with ethyl acetate (100ml * 3), separatory, the ethyl acetate layer anhydrous sodium sulfate drying, carry out underpressure distillation after the removal of solvent under reduced pressure, collect 155-157 ℃/533Pa cut, promptly 2,5-dimethoxy-phenylethylamine (12.2g), yield 67.4%.1H?NMR(CDCl
3，500MHz)δ：2.81(2H，t)，2.95(2H，m)，3.71-3.74(6H，s)，6.48-6.61(3H，m)。m/z：182.190(M+H)+。
Embodiment 2: a kind of 2 of present embodiment, the preparation method of 5-dimethoxy-phenylethylamine, other steps are identical with embodiment 1, it is the α-chloro-2 of A step, the preparation method of 5-dimethoxy-acetophenone is different from embodiment 1, α-the chloro-2 of the A step of present embodiment, the preparation method of 5-dimethoxy-acetophenone is as follows:
Reflux condensing tube is being housed, constant pressure funnel, add 1 in the 500ml three-necked bottle of thermometer and magnetic stirring apparatus, 4-dimethoxy benzene (60g, 0.44mol), methylene dichloride (240ml), after the stirring and dissolving, add boron trifluoride ether solution (100ml, about 0.48mol), finish the back and continued stirring at room 5 minutes, drip then chloroacetyl chloride (40ml, 0.5mol) and the mixed solution of methylene dichloride (40ml), dropwised in about 90 minutes, continued stirring at room then 4 hours, and poured into and continue in the 130ml concentrated hydrochloric acid that contains trash ice to stir 30 minutes, mixture extracts with methylene dichloride (100ml * 3), separatory, the dichloromethane layer anhydrous sodium sulfate drying obtains yellow solid after the removal of solvent under reduced pressure, be crude product.Crude product recrystallization in methyl alcohol obtains α-chloro-2,5-dimethoxy-acetophenone (63.6g), yield 67.4%, 89-91 ℃ of product fusing point (decomposition).
Embodiment 3: a kind of 2 of present embodiment, the preparation method of 5-dimethoxy-phenylethylamine, other steps are identical with embodiment 1, it is the α-chloro-2 of A step, the preparation method of 5-dimethoxy-acetophenone is different from embodiment 1, α-the chloro-2 of the A step of present embodiment, the preparation method of 5-dimethoxy-acetophenone is as follows:
Reflux condensing tube is being housed, constant pressure funnel, add 1 in the 500ml three-necked bottle of thermometer and magnetic stirring apparatus, 4-dimethoxy benzene (60g, 0.44mol), 1,2-ethylene dichloride (240ml), after the stirring and dissolving, (64g 0.48mol), finishes the back and continued stirring at room 5 minutes to add aluminum trichloride (anhydrous), drip chloroacetyl chloride (40ml then, 0.5mol) and the mixed solution of methylene dichloride (40ml), dropwised in about 90 minutes, continued stirring at room then 4 hours, pour into and continue in the 130ml concentrated hydrochloric acid that contains trash ice to stir 30 minutes, mixture extracts with methylene dichloride (100ml * 3), separatory, dichloromethane layer anhydrous sodium sulfate drying, obtain yellow solid after the removal of solvent under reduced pressure, be crude product.Crude product recrystallization in methyl alcohol obtains α-chloro-2,5-dimethoxy-acetophenone (60.3g), yield 65.4%, 89-91 ℃ of product fusing point (decomposition).
Embodiment 4: a kind of 2 of present embodiment, the preparation method of 5-dimethoxy-phenylethylamine, other steps are identical with embodiment 1, it is the α-chloro-2 of A step, the preparation method of 5-dimethoxy-acetophenone is different from embodiment 1, α-the chloro-2 of the A step of present embodiment, the preparation method of 5-dimethoxy-acetophenone is as follows:
Reflux condensing tube is being housed, constant pressure funnel, add 1 in the 500ml three-necked bottle of thermometer and magnetic stirring apparatus, 4-dimethoxy benzene (60g, 0.44mol), vinyl trichloride (240ml), after the stirring and dissolving, (64g 0.48mol), finishes the back and continued stirring at room 5 minutes to add aluminum trichloride (anhydrous), drip chloroacetyl chloride (40ml then, 0.5mol) and the mixed solution of vinyl trichloride (40ml), dropwised in about 90 minutes, continued stirring at room then 4 hours, and poured into and continue in the 130ml concentrated hydrochloric acid that contains trash ice to stir 30 minutes, mixture extracts with methylene dichloride (100ml * 3), separatory, the dichloromethane layer anhydrous sodium sulfate drying obtains yellow solid after the removal of solvent under reduced pressure, be crude product.Crude product recrystallization in methyl alcohol obtains α-chloro-2,5-dimethoxy-acetophenone (59.6g), yield 64.7%, 89-91 ℃ of product fusing point (decomposition).
Embodiment 5: a kind of 2 of present embodiment, the preparation method of 5-dimethoxy-phenylethylamine, other steps are identical with embodiment 1, it is the α-chloro-2 of A step, the preparation method of 5-dimethoxy-acetophenone is different from embodiment 1, α-the chloro-2 of the A step of present embodiment, the preparation method of 5-dimethoxy-acetophenone is as follows:
Reflux condensing tube is being housed, constant pressure funnel, add 1 in the 500ml three-necked bottle of thermometer and magnetic stirring apparatus, 4-dimethoxy benzene (60g, 0.44mol), methylene dichloride (240ml), after the stirring and dissolving, add aluminum trichloride (anhydrous) (64g, 0.48mol), finish the back and continued stirring at room 5 minutes, drip then chloroacetyl chloride (35.2ml, 0.44mol) and the mixed solution of methylene dichloride (40ml), dropwised in about 90 minutes, continued stirring at room then 4 hours, and poured into and continue in the 130ml concentrated hydrochloric acid that contains trash ice to stir 30 minutes, mixture extracts with methylene dichloride (100ml * 3), separatory, the dichloromethane layer anhydrous sodium sulfate drying obtains yellow solid after the removal of solvent under reduced pressure, be crude product.Crude product recrystallization in methyl alcohol obtains α-chloro-2,5-dimethoxy-acetophenone (58.4g), yield 63.5%, 89-91 ℃ of product fusing point (decomposition).
Embodiment 6: a kind of 2 of present embodiment, the preparation method of 5-dimethoxy-phenylethylamine, other steps are identical with embodiment 1, it is the α-chloro-2 of A step, the preparation method of 5-dimethoxy-acetophenone is different from embodiment 1, α-the chloro-2 of the A step of present embodiment, the preparation method of 5-dimethoxy-acetophenone is as follows:
Reflux condensing tube is being housed, constant pressure funnel, add 1 in the 500ml three-necked bottle of thermometer and magnetic stirring apparatus, 4-dimethoxy benzene (60g, 0.44mol), methylene dichloride (240ml), after the stirring and dissolving, add aluminum trichloride (anhydrous) (64g, 0.48mol), finish the back and continued stirring at room 5 minutes, drip then chloroacetyl chloride (52.8ml, 0.66mol) and the mixed solution of methylene dichloride (40ml), dropwised in about 90 minutes, continued stirring at room then 4 hours, and poured into and continue in the 130ml concentrated hydrochloric acid that contains trash ice to stir 30 minutes, mixture extracts with methylene dichloride (100ml * 3), separatory, the dichloromethane layer anhydrous sodium sulfate drying obtains yellow solid after the removal of solvent under reduced pressure, be crude product.Crude product recrystallization in methyl alcohol obtains α-chloro-2,5-dimethoxy-acetophenone (61.5g), yield 66.7%, 89-91 ℃ of product fusing point (decomposition).
Embodiment 7: a kind of 2 of present embodiment, the preparation method of 5-dimethoxy-phenylethylamine, other steps are identical with embodiment 1, it is the alpha-amino group-2 of B step, the preparation method of 5-dimethoxy-acetophenone is different from embodiment 1, the alpha-amino group-2 of the B step of present embodiment, the preparation method of 5-dimethoxy-acetophenone is as follows:
In being housed, the 500ml three-necked bottle of reflux condensing tube, thermometer and magnetic stirring apparatus adds α-chloro-2,5-dimethoxy-acetophenone (21.4g, 0.1mol) and concentration be 95% ethanol (200ml), add urotropine (14g after the stirring and dissolving, 0.1mol), stirring at room reaction 24 hours, reaction mixture is separated out a large amount of solids, and the stopped reaction after-filtration is collected solid.
Reflux condensing tube is being housed, add the above-mentioned solid that obtains in the 500ml three-necked bottle of thermometer and magnetic stirring apparatus, concentrated hydrochloric acid (100ml) and ethanol (100ml), reflux 24 hours, reaction end back slow adding concentration under the ice-water bath cooling conditions is 5% aqueous sodium hydroxide solution, regulating mixture pH is alkalescence, mixture extracts with ethyl acetate (100ml * 3) then, separatory, the ethyl acetate layer anhydrous sodium sulfate drying, obtain alpha-amino group-2 after the removal of solvent under reduced pressure, 5-methoxyacetophenone crude product (13.9g), content is greater than 96%, yield 71.4% need not be further purified and can be directly used in next step reaction.
Embodiment 8: a kind of 2 of present embodiment, the preparation method of 5-dimethoxy-phenylethylamine, other steps are identical with embodiment 1, it is the alpha-amino group-2 of B step, the preparation method of 5-dimethoxy-acetophenone is different from embodiment 1, the alpha-amino group-2 of the B step of present embodiment, the preparation method of 5-dimethoxy-acetophenone is as follows:
In being housed, the 500ml three-necked bottle of reflux condensing tube, thermometer and magnetic stirring apparatus adds α-chloro-2,5-dimethoxy-acetophenone (21.4g, 0.1mol) and concentration be 95% ethanol (200ml), add urotropine (70g after the stirring and dissolving, 0.5mol), stirring at room reaction 12 hours, reaction mixture is separated out a large amount of solids, and the stopped reaction after-filtration is collected solid.
Reflux condensing tube is being housed, add the above-mentioned solid that obtains in the 500ml three-necked bottle of thermometer and magnetic stirring apparatus, concentrated hydrochloric acid (100ml) and ethanol (100ml), reflux 24 hours, reaction end back slow adding concentration under the ice-water bath cooling conditions is 5% aqueous sodium hydroxide solution, regulating mixture pH is alkalescence, mixture extracts with ethyl acetate (100ml * 3) then, separatory, the ethyl acetate layer anhydrous sodium sulfate drying, obtain alpha-amino group-2 after the removal of solvent under reduced pressure, 5-dimethoxy-acetophenone crude product (14.5g), content is greater than 96%, yield 74.3% need not be further purified and can be directly used in next step reaction.
Embodiment 9: a kind of 2 of present embodiment, the preparation method of 5-dimethoxy-phenylethylamine, other steps are identical with embodiment 1, it is the alpha-amino group-2 of B step, the preparation method of 5-dimethoxy-acetophenone is different from embodiment 1, the alpha-amino group-2 of the B step of present embodiment, the preparation method of 5-dimethoxy-acetophenone is as follows:
In being housed, the 500ml three-necked bottle of reflux condensing tube, thermometer and magnetic stirring apparatus adds α-chloro-2,5-dimethoxy-acetophenone (21.4g, 0.1mol) and concentration be 95% ethanol (200ml), add urotropine (42g after the stirring and dissolving, 0.3mol), stirring at room reaction 18 hours, reaction mixture is separated out a large amount of solids, and the stopped reaction after-filtration is collected solid.
Reflux condensing tube is being housed, add the above-mentioned solid that obtains in the 500ml three-necked bottle of thermometer and magnetic stirring apparatus, concentrated hydrochloric acid (50ml) and ethanol (100ml), reflux 36 hours, reaction end back slow adding concentration under the ice-water bath cooling conditions is 5% aqueous sodium hydroxide solution, regulating mixture pH is alkalescence, mixture extracts with ethyl acetate (100ml * 3) then, separatory, the ethyl acetate layer anhydrous sodium sulfate drying, obtain alpha-amino group-2 after the removal of solvent under reduced pressure, 5-dimethoxy-acetophenone crude product (14.8g), content is greater than 96%, yield 75.9% need not be further purified and can be directly used in next step reaction.
Embodiment 10: a kind of 2 of present embodiment, the preparation method of 5-dimethoxy-phenylethylamine, other steps are identical with embodiment 1, it is the alpha-amino group-2 of B step, the preparation method of 5-dimethoxy-acetophenone is different from embodiment 1, the alpha-amino group-2 of the B step of present embodiment, the preparation method of 5-dimethoxy-acetophenone is as follows:
In being housed, the 500ml three-necked bottle of reflux condensing tube, thermometer and magnetic stirring apparatus adds α-chloro-2,5-dimethoxy-acetophenone (21.4g, 0.1mol) and concentration be 95% ethanol (200ml), add urotropine (42g after the stirring and dissolving, 0.3mol), stirring at room reaction 18 hours, reaction mixture is separated out a large amount of solids, and the stopped reaction after-filtration is collected solid.
Reflux condensing tube is being housed, add the above-mentioned solid that obtains in the 500ml three-necked bottle of thermometer and magnetic stirring apparatus, concentrated hydrochloric acid (150ml) and ethanol (100ml), reflux 12 hours, reaction end back slow adding concentration under the ice-water bath cooling conditions is 5% aqueous sodium hydroxide solution, regulating mixture pH is alkalescence, mixture extracts with ethyl acetate (100ml * 3) then, separatory, the ethyl acetate layer anhydrous sodium sulfate drying, obtain alpha-amino group-2 after the removal of solvent under reduced pressure, 5-dimethoxy-acetophenone crude product (15.2g), content is greater than 96%, yield 77.9% need not be further purified and can be directly used in next step reaction.
Embodiment 11: present embodiment a kind of 2, and the preparation method of 5-dimethoxy-phenylethylamine, other steps are identical with embodiment 1, it is 2 of C step, the preparation method of 5-dimethoxy-phenylethylamine is different from embodiment 1,2 of the C step of present embodiment, and the preparation method of 5-dimethoxy-phenylethylamine is as follows:
The reflux water-dividing device is being housed, add alpha-amino group-2 in the 1000ml three-necked bottle of thermometer and magnetic stirring apparatus, 5-dimethoxy-acetophenone (19.5g, 0.1mol), potassium hydroxide (33.6g, 0.6mol), ethylene glycol (240ml) and concentration are 80% hydrazine hydrate (38ml, about 0.6mol), stirring and refluxing is divided the water reaction, until the water of telling above theoretical amount, continue again to reflux 2 hours, have about 18 hours altogether, reaction finishes, reaction mixture is poured in the frozen water after being cooled to room temperature, and mixed solution extracts with ethyl acetate (100ml * 3), separatory, the ethyl acetate layer anhydrous sodium sulfate drying, carry out underpressure distillation after the removal of solvent under reduced pressure, collect 155-157 ℃/533Pa cut, promptly 2,5-dimethoxy-phenylethylamine (11.5g), yield 63.6%.
Embodiment 12: present embodiment a kind of 2, and the preparation method of 5-dimethoxy-phenylethylamine, other steps are identical with embodiment 1, it is 2 of C step, the preparation method of 5-dimethoxy-phenylethylamine is different from embodiment 1,2 of the C step of present embodiment, and the preparation method of 5-dimethoxy-phenylethylamine is as follows:
The reflux water-dividing device is being housed, add alpha-amino group-2 in the 1000ml three-necked bottle of thermometer and magnetic stirring apparatus, 5-dimethoxy-acetophenone (19.5g, 0.1mol), potassium hydroxide (33.6g, 0.6mol), glycol ether (240ml) and concentration are 80% hydrazine hydrate (13ml, about 0.2mol), stirring and refluxing is divided the water reaction, until the water of telling above theoretical amount, continue again to reflux 2 hours, have about 24 hours altogether, reaction finishes, reaction mixture is poured in the frozen water after being cooled to room temperature, and mixed solution extracts with ethyl acetate (100ml * 3), separatory, the ethyl acetate layer anhydrous sodium sulfate drying, carry out underpressure distillation after the removal of solvent under reduced pressure, collect 155-157 ℃/533Pa cut, promptly 2,5-dimethoxy-phenylethylamine (11.0g), yield 60.8%.
Embodiment 13: present embodiment a kind of 2, and the preparation method of 5-dimethoxy-phenylethylamine, other steps are identical with embodiment 1, it is 2 of C step, the preparation method of 5-dimethoxy-phenylethylamine is different from embodiment 1,2 of the C step of present embodiment, and the preparation method of 5-dimethoxy-phenylethylamine is as follows:
The reflux water-dividing device is being housed, add alpha-amino group-2 in the 1000ml three-necked bottle of thermometer and magnetic stirring apparatus, 5-dimethoxy-acetophenone (19.5g, 0.1mol), potassium hydroxide (33.6g, 0.6mol), glycol ether (240ml) and concentration are 80% hydrazine hydrate (50ml, about 0.8mol), stirring and refluxing is divided the water reaction, until the water of telling above theoretical amount, continue again to reflux 2 hours, have about 18 hours altogether, reaction finishes, reaction mixture is poured in the frozen water after being cooled to room temperature, and mixed solution extracts with ethyl acetate (100ml * 3), separatory, the ethyl acetate layer anhydrous sodium sulfate drying, carry out underpressure distillation after the removal of solvent under reduced pressure, collect 155-157 ℃/533Pa cut, promptly 2,5-dimethoxy-phenylethylamine (12.4g), yield 68.5%.
The above is preferred embodiment of the present invention only, is not to be used for limiting scope of the present invention, and is all according to equalization variation and modification that the present invention did, is all claim of the present invention and contains.
Claims (4)
1. one kind 2, the preparation method of 5-dimethoxy-phenylethylamine is characterized in that the 5-dimethoxy-phenylethylamine obtains according to following steps with 2 of formula (I) expression:
A. α-chloro-2, the preparation of 5-dimethoxy-acetophenone:
In reactor, add 1,1 part of 4-dimethoxy benzene, 1.0～1.5 parts of chloroacetyl chlorides, 6～9 parts of 1.1 parts of lewis acid catalysts and organic solvents, stir room temperature reaction, pour in 2～3 parts of the concentrated hydrochloric acids organic solvent extraction separatory after reaction finishes into, dry back removal of solvent under reduced pressure obtains the α-chloro-2 with formula (II) expression, 5-dimethoxy-acetophenone;
B. alpha-amino group-2, the preparation of 5-dimethoxy-acetophenone:
In reactor, add α-chloro-2,1 part of 5-dimethoxy-acetophenone, 1～5 part of urotropine, concentration is 8～12 parts of 95% ethanol, back flow reaction to a large amount of solids generate under agitation condition, stirring reaction finishes after-filtration and collects solid, then solid is dissolved in 5～15 parts of concentrated hydrochloric acids and the ethanol, back flow reaction, it is that 5% aqueous sodium hydroxide solution transfers to alkalescence with concentration that reaction finishes the cooling back, uses the ethyl acetate extraction separatory then, removal of solvent under reduced pressure after the ethyl acetate layer drying, obtain alpha-amino group-2, the 5-dimethoxy-acetophenone with formula (III) expression;
C.2, the preparation of 5-dimethoxy-phenylethylamine:
In reactor, add alpha-amino group-2,1 part of 5-dimethoxy-acetophenone, 1.5～2.5 parts in potassium hydroxide, 2～8 parts of 10～15 parts of organic solvents and hydrazine hydrates, stirring and refluxing reaction, reaction finish postcooling to room temperature and pour in the frozen water, the ethyl acetate extraction separatory, removal of solvent under reduced pressure after the ethyl acetate layer drying, underpressure distillation obtains 2, the 5-dimethoxy-phenylethylamine.
2. according to claim 1 a kind of 2, the preparation method of 5-dimethoxy-phenylethylamine is characterized in that lewis acid catalyst used in the described A step is any one in aluminum trichloride (anhydrous) or the boron trifluoride ether solution; Organic solvent is the alkyl chloride kind solvent, is methylene dichloride or 1,2-ethylene dichloride or vinyl trichloride; The consumption of chloroacetyl chloride is 1,1.1 times of the consumption of 4-dimethoxy benzene.
3. according to claim 1 a kind of 2, the preparation method of 5-dimethoxy-phenylethylamine, the consumption that it is characterized in that urotropine in the described B step is α-chloro-2,3 times of 5-dimethoxy-acetophenone, the reaction times is 12～24 hours; The consumption of concentrated hydrochloric acid is α-chloro-2,10 times of 5-dimethoxy-acetophenone, and reflux time is 12～36 hours.
4. according to claim 1 a kind of 2, the preparation method of 5-dimethoxy-phenylethylamine, it is characterized in that organic solvent used in the described C step is ethylene glycol or glycol ether, the consumption of hydrazine hydrate is an alpha-amino group-2,6 times of 5-dimethoxy-acetophenone, the reaction times is 12～24 hours.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008100616130A CN101311162B (en) | 2008-05-26 | 2008-05-26 | Method for preparing 2,5-dimethoxy phenylethylamine |
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| CN1434033A (en) * | 2003-02-14 | 2003-08-06 | 武汉大学 | 2,5-dimethoxy-4-ethyl phenethyl amine sulfide hydrochloride and preparation process and use thereof |
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Non-Patent Citations (4)
| Title |
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| 胡宏岗等.盐酸米多君的合成工艺改进.中国医药工业杂志37 7.2006,37(7),445-446. * |
| 黄洪霞等.2，5-二甲氧基苯乙胺的合成.精细化工中间体37 3.2007,37(3),70-72. |
| 黄洪霞等.2，5-二甲氧基苯乙胺的合成.精细化工中间体37 3.2007,37(3),70-72. * |
| 黄红霞等.3，4-二甲氧基苯乙胺的合成.科技与开发 5.2007,(5),10-11，30. * |
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