CN104030917A - Preparation method of amitriptyline hydrochloride intermediate o-phenethyl benzoic acid - Google Patents
Preparation method of amitriptyline hydrochloride intermediate o-phenethyl benzoic acid Download PDFInfo
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- CN104030917A CN104030917A CN201410255774.9A CN201410255774A CN104030917A CN 104030917 A CN104030917 A CN 104030917A CN 201410255774 A CN201410255774 A CN 201410255774A CN 104030917 A CN104030917 A CN 104030917A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/377—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
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Abstract
The invention discloses a preparation method of an amitriptyline hydrochloride intermediate o-phenethyl benzoic acid. The method comprises the following step: sequentially adding sodium o-phenylacetyl benzoate, purified water and a special catalyst in a weight ratio of 1:4:0.02 into a high-pressure reaction kettle. The special catalyst comprises 90-99% of nano nickel, 0.3-3.0% of cobalt, 0.2-2.0% of aluminum, 0.3-2.0% of iron and 0.2-2.0% of silicon. The method overcomes the defect of high-temperature high-pressure hydrogenation in the prior art, and implements low-temperature low-pressure hydrogenation; and the method enhances the synthesis yield and product purity. The maximum reaction temperature is lowered from 100 DEG C to 50 DEG C, the hydrogenation pressure is lowered from 20 kg/cm<2> to 5 kg/cm<2>, the product yield is enhanced from 88% to 98%, and the product purity is enhanced from 94% to 99%.
Description
Technical field:
The present invention relates to the benzoic preparation method of the adjacent styroyl of a kind of Warner) intermediate.
Background technology:
Adjacent styroyl phenylformic acid is the important intermediate of producing Warner), and existing preparation method has open in as Publication about Document:
At document one: Roberts, P.J.; Castar; J.; Cyclobenzaprine.DrugsFut1977, discloses the benzoic synthetic route of a kind of adjacent styroyl in 2,5,299, and its method is taking benzal phthalide as raw material, and red phosphorus is catalyzer, and back flow reaction in hydroiodic acid HI solution directly obtains adjacent styroyl phenylformic acid.The method is used red phosphorus, pollutes very seriously, and wastewater flow rate is processed greatly and very much; Reaction times needs 48 hours; Yield only has 80%.This scheme is because problem of environmental pollution is difficult to overcome, and current law restriction is used.
In document two,
Vilani; F.J.5-(3-Dimethylamino-2-methylpropyl) dizenzocycloheptenes.US3409640 discloses the benzoic synthetic route of a kind of adjacent styroyl; its method is taking benzal phthalide as raw material; obtain adjacent phenylacetyl Sodium Benzoate through hydrolysis; taking palladium carbon as catalyzer, obtain adjacent styroyl phenylformic acid through shortening.This section of document uses palladium carbon as catalyzer, and the method for High Temperature High Pressure hydrogenation is prepared adjacent styroyl phenylformic acid.The problem that the method exists is: reaction conditions is just carved, and need to make catalyzer with expensive palladium carbon, and temperature of reaction is that more than 100 DEG C reaction pressure is greater than 20Kg/cm
2, brought operational danger to production; The yield of reaction is only 88%, and the disposable purity of product is lower than 94%.
Summary of the invention:
The object of this invention is to provide the benzoic preparation method of the adjacent styroyl of a kind of Warner) intermediate.It is the further optimization to the second preparation method in prior art, and to reduce synthetic reaction condition, production cost, improves product yield and purity.
The technical scheme that the present invention takes is as follows:
In the autoclave of dried and clean, drop into successively adjacent phenylacetyl Sodium Benzoate, purified water and special-purpose catalyst, three's weight ratio is: 1:4:0.02; Close autoclave, with the air in pressure nitrogen gas displacement autoclave, after displacement thoroughly, pass into 5Kg/cm
2pressure hydrogen, open stir, while being warming up to 40 DEG C, carry out hydrogenation, when temperature rises to 50 DEG C, open water coolant, at hydrogen pressure 2Kg/cm
2～4Kg/cm
2under state, stop inhaling hydrogen, sampling detects material content, in the time that material content is less than 0.1%, and release discharging, filter, regulate PH=1～2 with reagent hydrochloric acid, filter, be dried to and lose that to be less than 0.5% be qualified, obtain adjacent styroyl phenylformic acid dry product, product yield reaches 98%, and purity is greater than 99%; Its composition of described special-purpose catalyst is: nano nickel: 90%～99%, and cobalt: 0.3%～3.0%, aluminium: 0.2%～2.0%; Iron: 0.3%～2.0%, silicon: 0.2%～2.0%.
Further, its composition of described special-purpose catalyst is: nano nickel: 95%～99%, and cobalt: 0.3%～1%, aluminium: 0.2%～1; Iron: 0.3%～1%, silicon: 0.2%～1%.
Further, its composition of described special-purpose catalyst is: nano nickel: 99%, and cobalt: 0.3%, aluminium: 0.2%; Iron: 0.3%, silicon: 0.2%.
The effect that the relatively existing technical solution of the present invention is obtained
Overcome prior art high-temperature high-pressure craft, not only realized low-temp low-pressure hydrogenation; And synthesis yield and product purity are improved.Reaction top temperature is down to 50 DEG C by 100 DEG C, and hydrogenation pressure is by 20Kg/cm
2be down to 5Kg/cm
2, product yield brings up to 98% by 88%, and tax on products purity brings up to 99% by 94%;
Brief description of the drawings:
Fig. 1 is synthetic route chart of the present invention.
Embodiment:
Embodiment 1:
In 500ml high-pressure hydrogenation still, drop into successively the adjacent phenylacetyl Sodium Benzoate of 50g, 200ml purified water, 1g special-purpose catalyst, installs autoclave, uses 2Kg/cm
2air in nitrogen replacement high-pressure hydrogenation still three times, passes into 5Kg/cm
2hydrogen, opens and stirs, and stirring velocity 200r/min, is warming up to 40 DEG C, starts to inhale hydrogen, when temperature rise to 50 DEG C, opens water coolant, at hydrogen pressure 2Kg/cm
2under state, stop inhaling hydrogen, sampling detection raw material sheds the pressure in autoclave while being less than 0.1%, open autoclave, discharging, filter, with reagent hydrochloric acid adjusting pH value to 1～1.5, filter, to dry qualified while losing < 0.5%, obtain purity and be 99% dry product 42.3g with 80 DEG C of forced air dryings.
Embodiment 2:
In 500ml high-pressure hydrogenation still, drop into successively the adjacent phenylacetyl Sodium Benzoate of 50g, 200ml purified water, 1g special-purpose catalyst, installs autoclave, 2Kg/cm
2nitrogen replacement three times, passes into 5Kg/cm
2hydrogen, opens and stirs, and stirring velocity 200r/min, is warming up to 40 DEG C, starts to inhale hydrogen, when temperature rise to 50 DEG C, opens water coolant, at hydrogen pressure 3Kg/cm
2state stops inhaling hydrogen, and sampling detects raw material < 0.1%, sheds the pressure in autoclave, opens autoclave, discharging, filters, and regulates PH=1～1.5 with reagent hydrochloric acid, filter, qualified while losing < 0.5% with 80 DEG C of forced air dryings are extremely dry, obtain 43g dry product.
Embodiment 3: in 500ml high-pressure hydrogenation still, drop into successively the adjacent phenylacetyl Sodium Benzoate of 50g, 200ml purified water, 1g special-purpose catalyst, installs autoclave, 2Kg/cm
2nitrogen replacement three times, passes into 5Kg/cm
2hydrogen, opens and stirs, and stirring velocity 200r/min, is warming up to 40 DEG C, starts to inhale hydrogen, when temperature rise to 50 DEG C, opens water coolant, keeps 4Kg/cm at hydrogen pressure
2under state, stop inhaling hydrogen, sampling detects raw material < 0.1%, sheds the pressure in autoclave, opens autoclave, discharging, filters, and regulates PH=1 with reagent hydrochloric acid, filter, qualified while losing < 0.5% with 80 DEG C of forced air dryings are extremely dry, obtain 43.3g dry product.
In above-mentioned three embodiment, the component of described special-purpose catalyst and weight percent are: nano nickel, 99%; Cobalt, 0.3%; Aluminium, 0.2%; Iron, 0.3%; Silicon, 0.2%.
The content of nano nickel, cobalt and silicon is higher, and catalytic effect is better, and aluminium, iron level height are inverse ratio with catalytic effect.
Claims (3)
1. the benzoic preparation method of the adjacent styroyl of Warner) intermediate, is characterized in that: in the autoclave of dried and clean, drop into successively adjacent phenylacetyl Sodium Benzoate, purified water and special-purpose catalyst, three's weight ratio is: 1:4:0.02; Close autoclave, with the air in pressure nitrogen gas displacement autoclave, after displacement thoroughly, pass into 5Kg/cm
2pressure hydrogen, open stir, while being warming up to 40 DEG C, carry out hydrogenation, when temperature rises to 50 DEG C, open water coolant, at hydrogen pressure 2Kg/cm
2～4Kg/cm
2under state, stop inhaling hydrogen, sampling detects material content, in the time that material content is less than 0.1%, and release discharging, filter, regulate PH=1～2 with reagent hydrochloric acid, filter, be dried to and lose that to be less than 0.5% be qualified, obtain adjacent styroyl phenylformic acid dry product, product yield reaches 98%, and purity is greater than 99%; The component of described special-purpose catalyst and weight percent are: nano nickel, 90%～99%; Cobalt, 0.3%～3.0%; Aluminium, 0.2%～2.0%; Iron, 0.3%～2.0%; Silicon, 0.2%～2.0%.
2. the benzoic preparation method of the adjacent styroyl of Warner) intermediate according to claim 1, is characterized in that: its component and the weight percent thereof of described special-purpose catalyst are: nano nickel, 95%～99%; Cobalt, 0.3%～1%; Aluminium, 0.2%～1; Iron, 0.3%～1%; Silicon, 0.2%～1%.
3. the benzoic preparation method of the adjacent styroyl of Warner) intermediate according to claim 2, is characterized in that: its composition of described special-purpose catalyst is: nano nickel: 99%, and cobalt: 0.3%, aluminium: 0.2%; Iron: 0.3%, silicon: 0.2%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410255774.9A CN104030917A (en) | 2014-06-10 | 2014-06-10 | Preparation method of amitriptyline hydrochloride intermediate o-phenethyl benzoic acid |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410255774.9A CN104030917A (en) | 2014-06-10 | 2014-06-10 | Preparation method of amitriptyline hydrochloride intermediate o-phenethyl benzoic acid |
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| CN104030917A true CN104030917A (en) | 2014-09-10 |
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| CN201410255774.9A Pending CN104030917A (en) | 2014-06-10 | 2014-06-10 | Preparation method of amitriptyline hydrochloride intermediate o-phenethyl benzoic acid |
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Application publication date: 20140910 |
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| WD01 | Invention patent application deemed withdrawn after publication |