CN111377829A - Preparation method of 7-methoxy-1-naphthylacetonitrile - Google Patents

Preparation method of 7-methoxy-1-naphthylacetonitrile Download PDF

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CN111377829A
CN111377829A CN202010277544.8A CN202010277544A CN111377829A CN 111377829 A CN111377829 A CN 111377829A CN 202010277544 A CN202010277544 A CN 202010277544A CN 111377829 A CN111377829 A CN 111377829A
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methoxy
naphthylacetonitrile
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reaction
naphthaleneacetonitrile
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沈建伟
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Suzhou Jingye Medicine & Chemical Co ltd
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Suzhou Jingye Medicine & Chemical Co ltd
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00Preparation of carboxylic acid nitriles
    • C07C253/30Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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    • Y02PCLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00Technologies relating to chemical industry
    • Y02P20/50Improvements relating to the production of bulk chemicals
    • Y02P20/584Recycling of catalysts

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Abstract

The invention discloses a preparation method of 7-methoxy-1-naphthylacetonitrile, which is characterized by adding 7-methoxy-3, 4-dihydro-1-naphthylacetonitrile into a first solvent for dissolving, adding allyl methacrylate, stirring uniformly, adding a catalyst ruthenium/carbon, and carrying out dehydroaromatization reaction; after the reaction is finished, filtering the catalyst, adding a second solvent into the filtrate after decompression and desolventization, heating and dissolving, cooling, crystallizing, filtering, and drying to obtain the white crystal 7-methoxy-1-naphthylacetonitrile. The preparation method of the 7-methoxy-1-naphthylacetonitrile provided by the invention is simple to operate, less in pollution, low in cost, high in yield, less in side reaction, high in product purity, and reusable in catalyst.

Description

Preparation method of 7-methoxy-1-naphthylacetonitrile
Technical Field
The invention relates to the technical field of drug synthesis, in particular to a preparation method of 7-methoxy-1-naphthylacetonitrile.
Background
7-methoxy-1-naphthylacetonitrile, the molecular structural formula is as follows:
Figure DEST_PATH_IMAGE001
the molecular formula is as follows: c13H11NO; CAS number: 138113-08-3.
The 7-methoxy-1-naphthylacetonitrile is a key intermediate for synthesizing the agomelatine. Agomelatine (agomelatine), with the chemical name of N- [2- (7-methoxy-1-naphthyl) ethyl ] acetamide, is the first melatonin antidepressant drug and can effectively treat depression, improve sleep parameters and maintain sexual function. Are now marketed in several countries worldwide for the treatment of adult patients with depression.
The 7-methoxy-1-naphthylacetonitrile is synthesized from 7-methoxy-3, 4-dihydro-1-naphthylacetonitrile, and the following methods are mainly adopted:
1) chinese patents CN201310074356.5 and CN201710463834.X both disclose a synthesis method of 7-methoxy-1-naphthylacetonitrile, which adopts 7-methoxy-3, 4-dihydro-1-naphthylacetonitrile as a starting material, and adopts dichlorodicyanobenzoquinone (DDQ) to perform dehydroaromatization in halohydrocarbon to prepare the 7-methoxy-1-naphthylacetonitrile; the by-product produced by the method is mainly DDQ reduced into DDHQ (dichloro dicyano hydroquinone), and the method has serious environmental pollution and poor quality.
2) Chinese patent CN200510071611.6 discloses a new synthesis method of agomelatine, a new crystal form and a pharmaceutical composition thereof, the invention adopts 7-methoxy-3, 4-dihydro-1-naphthylacetonitrile as a raw material, and dehydroaromatization is carried out in toluene by using 10% Pd/C and allyl methacrylate; the method mainly has the defects of high Pd/C price, easy poisoning and incapability of recycling, thus causing higher production cost of products.
3) The invention patent WO2014/064706 adopts 7-hydroxy-3, 4-dihydro-1-naphthylacetonitrile as a raw material, Pd/C and allyl methacrylate are used for dehydroaromatization in toluene, and then hydroxy methylation is carried out to synthesize the 7-methoxy-1-naphthylacetonitrile; the method also has the disadvantages of high Pd/C price, easy poisoning and incapability of recycling, thus causing higher production cost.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides the preparation method of the 7-methoxy-1-naphthylacetonitrile, which has the advantages of simple operation, less pollution, low cost, high yield, less side reaction, high product purity and reusable catalyst.
In order to realize the aim, the technical scheme of the invention is to design a preparation method of 7-methoxy-1-naphthylacetonitrile, which is characterized in that 7-methoxy-3, 4-dihydro-1-naphthylacetonitrile is added into a first solvent to be dissolved, allyl methacrylate is added to be uniformly stirred, and then catalyst ruthenium/carbon is added to carry out dehydroaromatization reaction;
the chemical reaction formula of the dehydroaromatization reaction is as follows:
Figure DEST_PATH_IMAGE003
after the reaction is finished, filtering the catalyst, adding a second solvent into the filtrate after decompression and desolventization, heating and dissolving, cooling, crystallizing, filtering, and drying to obtain the white crystal 7-methoxy-1-naphthylacetonitrile.
Preferably, the first solvent is an alcohol solvent or an aromatic hydrocarbon solvent.
Preferably, the alcohol solvent is methanol, ethanol, propanol or isopropanol.
Preferably, the aromatic hydrocarbon solvent is benzene, toluene or xylene.
Preferably, the mass ratio of the 7-methoxy-3, 4-dihydro-1-naphthylacetonitrile to the first solvent is 1: 4-15.
Preferably, the molar ratio of the 7-methoxy-3, 4-dihydro-1-naphthaleneacetonitrile to the allyl methacrylate is 1: 1-3.
Preferably, the mass ratio of the 7-methoxy-3, 4-dihydronaphthalene acetonitrile to the catalyst is 1: 0.02-0.1.
Preferably, the reaction temperature of the dehydroaromatization reaction is 40-120 ℃, and the reaction time is 2-10 hours.
Preferably, the second solvent is methanol, ethanol, propanol or isopropanol.
The invention has the advantages and beneficial effects that: the invention provides a preparation method of 7-methoxy-1-naphthylacetonitrile, which has the advantages of simple operation, less pollution, low cost, high yield, less side reaction, high product purity and reusable catalyst; the mild dehydrogenation condition is adopted, the catalyst can be repeatedly applied for 10 times, the process operation is optimized, the product quality is improved, the one-time crystallization content of the product is more than 99.0 percent, the yield is improved, and the yield reaches more than 95 percent.
The product obtained by the invention has good chroma, high purity, high yield, recyclable catalyst, less pollution and reduced production cost.
The invention overcomes the problems of poor product quality (color), serious pollution, difficult treatment of three wastes, difficult catalyst recycling and high production cost in the prior art.
The method for synthesizing the 7-methoxy-1-naphthylacetonitrile mainly adopts ruthenium/carbon and methacrylic acid allyl propionate instead of DDQ or palladium/carbon, and has the characteristics of milder and safer reaction conditions, high yield, low cost, good quality and the like.
Detailed Description
The following further describes embodiments of the present invention with reference to examples. The following examples are only for illustrating the technical solutions of the present invention more clearly, and the protection scope of the present invention is not limited thereby.
Example 1
Adding 50.0g (0.25 mol) of 7-methoxy-3, 4-dihydro-1-naphthacenitrile and 350ml of toluene into a 500ml four-neck flask, and stirring to dissolve; 42.5g (0.34 mol) of allyl methacrylate is added and stirred for 10 min; then adding 2.5g of 5 percent ruthenium/carbon; heating to 80 deg.C, stirring and reacting for 4 hrs; sampling and GC analysis: the normalized content of the raw materials is 0.5 percent, and the reaction is finished;
after the reaction is finished, cooling to room temperature, carrying out suction filtration, washing with a small amount of toluene, and recycling the catalyst; mixing the filtrate and washing liquid, removing solvent under reduced pressure to dry, adding 300ml65% ethanol water solution into the residual liquid, heating to 65 deg.C for dissolving, cooling to 0 deg.C, stirring and crystallizing for 1 hr; performing suction filtration, washing with 50% ethanol water solution, and drying the solid to obtain 47.6g of 7-methoxy-1-naphthylacetonitrile with the content of 99.3% and the yield of 96.2%; nuclear magnetic analysis of the product, its hydrogen spectrum 1HNMR (CDCl 3): 3.94 (s, 3H), 4.05 (s, 2H), 7.05 (d, J =2.1Hz, 1H), 7.20 ~ 7.81 (m, 5H).
Examples 2 to 5:
the following examples 2 to 5 were all operated according to the procedure of example 1, and only the catalyst ruthenium carbon was reused for different times, and the implementation results are shown in the following table:
examples 2 to 5 Experimental results
Example number Number of recycling of ruthenium/carbon Reaction time (hr) Product content (%) Yield (%)
2 For the second time 4.0 99.2 95.1
3 The third time 5.0 99.0 95.4
4 Fourth time 4.0 99.1 96.5
5 Fifth time 5.0 99.4 96.3
Example 6
Adding 50.0g (0.25 mol) of 7-methoxy-3, 4-dihydro-1-naphthacenitrile and 350ml of absolute ethyl alcohol into a 500ml four-mouth bottle, and stirring for dissolving; 42.5g (0.34 mol) of allyl methacrylate is added and stirred for 10 min; then adding 2.5g of 5 percent ruthenium/carbon; heating to 70 deg.C, stirring and reacting for 6 hrs; sampling and GC analysis: the normalized content of the raw materials is 0.6 percent, and the reaction is finished;
after the reaction is finished, cooling to room temperature, carrying out suction filtration, washing with a small amount of ethanol, and recycling the catalyst; mixing the filtrate and washing liquid, removing solvent under reduced pressure to dry, adding 300ml65% ethanol water solution into the residual liquid, heating to 65 deg.C for dissolving, cooling to 0 deg.C, stirring and crystallizing for 1 hr; and (3) carrying out suction filtration, washing by using a 50% ethanol water solution, and drying the solid to obtain 46.8g of the product 7-methoxy-1-naphthylacetonitrile with the content of 99.5% and the yield of 94.7%.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the technical principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.

Claims (9)

1. A preparation method of 7-methoxy-1-naphthylacetonitrile is characterized in that 7-methoxy-3, 4-dihydro-1-naphthylacetonitrile is added into a first solvent to be dissolved, allyl methacrylate is added, the mixture is stirred uniformly, and a catalyst ruthenium/carbon is added to perform dehydroaromatization reaction; after the reaction is finished, filtering the catalyst, adding a second solvent into the filtrate after decompression and desolventization, heating and dissolving, cooling, crystallizing, filtering, and drying to obtain the white crystal 7-methoxy-1-naphthylacetonitrile.
2. The method for preparing 7-methoxy-1-naphthaleneacetonitrile according to claim 1, wherein the first solvent is an alcohol solvent or an aromatic hydrocarbon solvent.
3. The method for producing 7-methoxy-1-naphthaleneacetonitrile according to claim 2, wherein the alcoholic solvent is methanol, ethanol, propanol, or isopropanol.
4. The method for producing 7-methoxy-1-naphthaleneacetonitrile according to claim 2, characterized in that the aromatic hydrocarbon solvent is benzene, toluene or xylene.
5. The method for preparing 7-methoxy-1-naphthylacetonitrile according to claim 1, wherein the mass ratio of 7-methoxy-3, 4-dihydro-1-naphthylacetonitrile to the first solvent is 1:4 to 15.
6. The method for producing 7-methoxy-1-naphthaleneacetonitrile according to claim 1, wherein the molar ratio of 7-methoxy-3, 4-dihydro-1-naphthaleneacetonitrile to allyl methacrylate is 1:1 to 3.
7. The method for preparing 7-methoxy-1-naphthylacetonitrile according to claim 1, wherein the mass ratio of 7-methoxy-3, 4-dihydronaphthylacetonitrile to the catalyst is 1: 0.02-0.1.
8. The method for preparing 7-methoxy-1-naphthaleneacetonitrile according to claim 1, wherein the reaction temperature of the dehydroaromatization reaction is 40 to 120 ℃ and the reaction time is 2 to 10 hours.
9. The method of preparing 7-methoxy-1-naphthaleneacetonitrile according to claim 1, wherein the second solvent is methanol, ethanol, propanol, or isopropanol.
CN202010277544.8A 2020-04-10 2020-04-10 Preparation method of 7-methoxy-1-naphthylacetonitrile Pending CN111377829A (en)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1680297A (en) * 2004-02-13 2005-10-12 瑟维尔实验室 New process for the synthesis of (7-methoxy-1-naphthyl)acetonitrile and its application in the synthesis of agomelatine
CN102633710A (en) * 2012-03-29 2012-08-15 南通海迪化工有限公司 Method for synthesizing carbazole compounds

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1680297A (en) * 2004-02-13 2005-10-12 瑟维尔实验室 New process for the synthesis of (7-methoxy-1-naphthyl)acetonitrile and its application in the synthesis of agomelatine
CN102633710A (en) * 2012-03-29 2012-08-15 南通海迪化工有限公司 Method for synthesizing carbazole compounds

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Application publication date: 20200707