CN111004250B - Synthetic method of 1, 4-epoxy-2, 3-dicyano-1, 2,3, 4-tetrahydronaphthalene - Google Patents
Synthetic method of 1, 4-epoxy-2, 3-dicyano-1, 2,3, 4-tetrahydronaphthalene Download PDFInfo
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- CN111004250B CN111004250B CN201911378872.0A CN201911378872A CN111004250B CN 111004250 B CN111004250 B CN 111004250B CN 201911378872 A CN201911378872 A CN 201911378872A CN 111004250 B CN111004250 B CN 111004250B
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- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
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Abstract
The invention discloses a method for synthesizing 1, 4-epoxy-2, 3-dicyano-1, 2,3, 4-tetrahydronaphthalene, which comprises the following steps: and cyclizing and decarboxylating the ethyl 2, 3-dicyano acrylate 1G and the 1-methoxy-1, 3-dihydrobenzo-2-furan 1C under the catalysis of a decarboxylating agent to prepare the 1, 4-epoxy-2, 3-dicyano-1, 2,3, 4-tetrahydronaphthalene 1D. The invention takes cheap 2, 3-dicyano ethyl propionate 1E as the initial raw material, and the 2, 3-dicyano ethyl acrylate 1G is obtained by halogenation and elimination; then the intermediate and 1-methoxyl-1, 3-dihydro-2-benzofuran 1C are subjected to cyclization reaction, and a decarboxylation process is carried out at the same time, so that a target product is obtained. The method has the advantages of cheap and easily obtained raw materials, mild reaction conditions, thorough reaction in each step, few byproducts, simple separation, direct entering of the next step, simple and convenient operation, high yield, low production cost and environmental friendliness.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and relates to a synthesis method of 1, 4-epoxy-2, 3-dicyano-1, 2,3, 4-tetrahydronaphthalene.
Background
1, 4-epoxy-2, 3-dicyano-1, 2,3, 4-tetrahydronaphthalene (1D) is an important intermediate for the manufacture of ink-based organic materials, and has a long-term and stable demand in the international market. The existing and mature manufacturing process route of the product is to take diethyl fumarate (1A) as a raw material, obtain 1, 4-butenedionitrile (1B) through ammonolysis and dry distillation, and then react with 1-methoxy-1, 3-dihydro-2-benzofuran (1C) to obtain a target product. The corresponding reaction equation is as follows:
in the above process route, 1, 4-butenedionitrile (1B) is prepared by using a large amount of phosphorus pentoxide and dry distilling at 250 ℃ or higher. The process not only consumes a large amount of phosphorus pentoxide and generates a large amount of waste phosphoric acid, but also has extremely high environmental protection treatment cost; and needs special dry distillation equipment which can bear strong acid corrosion under high temperature condition and realize strict inert gas protection; and the problems of pipeline blockage due to material solidification, raw material carbonization, odor and the like easily occur in the dry distillation process.
With the enhancement of environmental protection consciousness in China and all over the world, the technological process is difficult to obtain production permission due to high energy consumption, high pollution and high corrosion; meanwhile, the required phosphorus pentoxide is also controlled by environmental protection, so that the market supply is reduced and the price is increased.
Therefore, there is a need to develop a low-pollution production process of 1, 4-epoxy-2, 3-dicyano-1, 2,3, 4-tetrahydronaphthalene.
Disclosure of Invention
The invention aims to solve the problems that the existing synthesis process of 1, 4-epoxy-2, 3-dicyano-1, 2,3, 4-tetrahydronaphthalene is not environment-friendly and has high requirements on equipment, high energy consumption, high pollution and high corrosion, and designs a new process route, wherein 2, 3-dicyano ethyl propionate 1E is used as a raw material, and 2, 3-dicyano ethyl acrylate 1G is obtained by halogenation and elimination; then reacting with 1-methoxy-1, 3-dihydro-2-benzofuran (1C) and simultaneously carrying out decarboxylation to obtain the target product. The method is environment-friendly, mild in process conditions and low in production cost.
In order to achieve the above objects, the present invention provides a method for synthesizing 1, 4-epoxy-2, 3-dicyano-1, 2,3, 4-tetrahydronaphthalene, comprising: the ethyl 2, 3-dicyano acrylate 1G and 1-methoxy-1, 3-dihydrobenzo-2-furan 1C are cyclized and decarboxylated under the catalysis of a decarboxylating agent to prepare 1, 4-epoxy-2, 3-dicyano-1, 2,3, 4-tetrahydronaphthalene 1D, and the reaction formula is as follows:
optionally, the ratio of the ethyl 2, 3-dicyano acrylate 1G to the 1-methoxy-1, 3-dihydrobenzo-2-furan 1C is 1 (1-1.5) in terms of molar ratio.
Optionally, the decarboxylating agent is acetic anhydride, and the dosage of the acetic anhydride is 1-10 times, preferably 1-5 times, more preferably 1-2 times of that of ethyl 2, 3-dicyanoacrylate 1G, in terms of molar ratio.
Alternatively, the reaction temperature is heated to reflux and acetic anhydride is added dropwise or in portions.
Alternatively, the ethyl 2, 3-dicyanoacrylate 1G is prepared from ethyl 2-halo-2, 3-dicyanoacrylate 1F by elimination, which has the following reaction formula:
wherein X ═ Cl or Br.
Alternatively, the elimination reaction employs a weakly basic material containing no water as a catalyst.
Optionally, the catalyst is selected from any one or combination of any more of triethylamine, pyridine, triethylene diamine, sodium acetate, potassium acetate and DMF.
Optionally, the amount of the catalyst is 1-5 times, preferably 1-2 times, in terms of molar ratio, that of ethyl 2-halo-2, 3-dicyanopropionate 1F; in the elimination reaction, the dropping speed of the catalyst is controlled so that the liquid temperature does not exceed minus 5 ℃; after the dropwise addition is finished, the reaction is continued for 1 to 3 hours at the temperature of between 10 ℃ below zero and 5 ℃ below zero.
Alternatively, ethyl 2-halo-2, 3-dicyanopropionate 1F is prepared from ethyl 2, 3-dicyanopropionate 1E by halogenation, which is represented by the formula:
alternatively, the halogenation reaction comprises: adding a halogenating reagent slowly into an aqueous solution of 2, 3-dicyanopropionic acid ethyl ester 1E under the stirring condition of 0-10 ℃, and reacting for 1-5h, wherein the halogenating reagent is selected from the group consisting of: chlorine, bromine, hydrochloric acid and hypochlorous acid mixtures, mixtures of bromine or hydrobromic acid with any of hypobromous acid, sodium bromate and sodium perborate.
The invention has the technical effects that:
1) the starting material 2, 3-dicyanopropionic acid ethyl ester 1E adopted by the invention has sufficient market supply and is cheap;
2) the invention avoids the high energy consumption and high pollution process in the existing mature process route by relatively environment-friendly and mild process procedures and conditions; the invention has no special requirements on process equipment, and can be realized by using common chemical equipment.
3) The method has the advantages of mild reaction route conditions, thorough reaction in each step, few byproducts, no need of complex post-treatment, simple separation, capability of entering the next step, simple and convenient operation and high yield.
Detailed Description
The following examples illustrate the invention in detail: the embodiment is implemented on the premise of the technical scheme of the invention, and a detailed implementation mode and a specific operation process are given. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention.
As used herein, "liquid temperature" refers to the temperature of a solution.
The technical conception of the invention is as follows: taking cheap 2, 3-dicyano ethyl propionate 1E as a raw material, and firstly halogenating and eliminating to obtain 2, 3-dicyano ethyl acrylate 1G; then reacting with 1-methoxy-1, 3-dihydro-2-benzofuran 1C, and simultaneously performing decarboxylation to obtain a target product, wherein the specific synthetic route is as follows:
in the halogenation reaction from the compound 1E to the compound 1F, the adopted halogen can be chlorine or bromine; the reaction conditions for halogenation can be any of the classical and common reaction conditions for chlorination or bromination in the alpha-position of the carbonyl group, for example, the halogenating agent can be chlorine gas, bromine, a mixture of hydrochloric acid and hypochlorous acid, a mixture of bromine (or hydrobromic acid) and any of hypobromous acid, sodium bromate and sodium perborate, and the like. The amount of the halogenated agent used may be in excess as required in accordance with the stoichiometric ratio of the reaction equation. The halogenation reaction is relatively thorough, the byproducts are few, and the crude product can be applied to the next step only by simple separation after the reaction is finished.
The elimination reaction from the compound 1F to the compound 1G can be carried out under various classical and common hydrogen halide elimination reaction conditions, and the catalyst can be any one or a mixture of any more of water-free weakly basic substances such as triethylamine, pyridine, triethylenediamine, sodium acetate, potassium acetate, DMF (N, N-dimethylformamide) and the like. The dosage of the catalyst is 1-5 times, preferably 1-2 times of that of 2-halogenated-2, 3-dicyanopropionic acid ethyl ester 1F, and the dosage is calculated by a molar ratio; in the elimination reaction, the dropping speed of the catalyst is controlled so that the liquid temperature does not exceed minus 5 ℃; after the dropwise addition is finished, the reaction is continued for 1 to 3 hours at the temperature of between 10 ℃ below zero and 5 ℃ below zero. The elimination reaction is relatively thorough, the byproducts are few, and the crude product can be applied to the next step only by simple separation after the reaction is finished.
And (3) adding the compound 1G and the compound 1C into a ring under the action of a decarboxylating agent such as acetic anhydride, and removing carboxyl at the same time to obtain a target product 1D. Wherein, the acetic anhydride also plays a role in promoting the compound 1C to carry out elimination reaction, removing one methanol molecule and forming furan ring intermediate product. The amount of acetic anhydride is 1 to 10 times, preferably 1 to 5 times, more preferably 1 to 2 times the amount of ethyl 2, 3-dicyanoacrylate 1G. The dosage ratio of the ethyl 2, 3-dicyano acrylate 1G and the 1-methoxy-1, 3-dihydrobenzo-2-furan 1C is determined according to the stoichiometric ratio of the reaction equation, and the 1C can be properly excessive according to the requirement, and the preferable ratio is 1 (1-1.5) in terms of molar ratio. The cyclization reaction is relatively thorough, byproducts are few, and after the reaction is finished, only simple separation is needed, so that the purity of a crude product is very high, and the subsequent further purification is convenient.
The following examples are provided to illustrate the synthesis of 1, 4-epoxy-2, 3-dicyano-1, 2,3, 4-tetrahydronaphthalene according to the present invention.
Examples
The synthetic route is shown as the following formula:
preparation of S1, ethyl 2-bromo-2, 3-dicyanopropionate (1F, X ═ Br):
to a 500ml three-necked glass bottle was added 30.4g (0.2mol) of ethyl 2, 3-dicyanopropionate in this order (b: (a))1E) 300g of water. Cooling the reaction solution to 0-10 ℃ under stirring; 32g (0.2mol) of bromine (Br) was added dropwise to the reaction solution2) Controlling the dropping speed to ensure that the liquid temperature does not exceed 10 ℃; after the dropwise addition, the temperature is kept between 0 and 10 ℃ and the stirring reaction is carried out for 4 hours. Then, the mixture was allowed to stand for liquid separation. The organic layer was sampled and analyzed by gas chromatography, and the result showed that the content of the target product ethyl 2-bromo-2, 3-dicyanopropionate (1F) of this reaction was 91.22%, and it could be directly fed to the next reaction.
Preparation of S2, ethyl 2, 3-dicyanoacrylate (1G):
adding the organic layer in the last step into a 500ml three-mouth glass bottle, and cooling to below-10 ℃. Dissolving 20.2g (0.2mol) of triethylamine in 50ml of toluene, slowly dripping into the reaction solution, and controlling the dripping speed to ensure that the liquid temperature does not exceed minus 5 ℃; after the dropwise addition is finished, the reaction is continued for 1 hour at the temperature of minus 10 to minus 5 ℃. 200ml of water was added to the reaction mixture, and the mixture was stirred for 10 minutes, and then allowed to stand for liquid separation. The organic layer was washed with water to neutrality. Reduced pressure distillation is carried out to remove toluene, and 23G of dark red oily matter is obtained, namely the crude product of the target product, namely the ethyl 2, 3-dicyanoacrylate (1G) of the reaction; sampling and carrying out gas chromatography analysis, wherein the purity of the sample is 82.4%; can be directly used for the next reaction.
S3, 1, 4-epoxy-2, 3-dicyano-1, 2,3, 4-tetrahydronaphthalene (1D):
to a 500ml three-necked glass bottle, were added in sequence: 23G (0.15mol) of ethyl 2, 3-dicyanoacrylate (1G) as the product of the previous step, 30.4G (0.2mol) of 1-methoxy-1, 3-dihydrobenzo-2-furan (1C), and 150ml of xylene. Stirring was started, the temperature was raised to 120 ℃ to reflux, and 20.4g (0.2mol) of acetic anhydride was added dropwise to the reaction mixture over about 40 minutes. After the addition, the reaction was refluxed for 4 hours. After the reaction, the reaction solution was cooled to 25 ℃ for crystallization, and 21.2g of crude 1, 4-epoxy-2, 3-dicyano-1, 2,3, 4-tetrahydronaphthalene (1D) was obtained by suction filtration with a yield of 70.6%. A sample was taken and analyzed by gas chromatography, and the purity thereof was 98.2%.
In conclusion, the invention takes cheaper 2, 3-dicyano ethyl propionate 1E as raw material, and the 2, 3-dicyano ethyl propionate 1G is obtained by halogenating and eliminating; then the intermediate and 1-methoxyl-1, 3-dihydro-2-benzofuran 1C are subjected to cyclization reaction, and a decarboxylation process is carried out at the same time, so that a target product is obtained. The method has the advantages of cheap and easily obtained raw materials, mild reaction conditions, thorough reaction in each step, few byproducts, simple separation, direct entering of the next step, simple and convenient operation, high yield, low production cost and environmental friendliness.
While the present invention has been described in detail with reference to the preferred embodiments, it should be understood that the above description should not be taken as limiting the invention. Various modifications and alterations to this invention will become apparent to those skilled in the art upon reading the foregoing description. Accordingly, the scope of the invention should be determined from the following claims.
Claims (10)
1. A method for synthesizing 1, 4-epoxy-2, 3-dicyano-1, 2,3, 4-tetrahydronaphthalene, comprising: the ethyl 2, 3-dicyano acrylate 1G and 1-methoxy-1, 3-dihydrobenzo-2-furan 1C are cyclized and decarboxylated under the catalysis of a decarboxylating agent to obtain 1, 4-epoxy-2, 3-dicyano-1, 2,3, 4-tetrahydronaphthalene 1D, and the reaction formula is as follows:
2. the method for synthesizing 1, 4-epoxy-2, 3-dicyano-1, 2,3, 4-tetrahydronaphthalene according to claim 1, wherein the ratio of the ethyl 2, 3-dicyano acrylate 1G to the 1-methoxy-1, 3-dihydrobenzo-2-furan 1C is 1 (1-1.5) in terms of molar ratio.
3. The method for synthesizing 1, 4-epoxy-2, 3-dicyano-1, 2,3, 4-tetrahydronaphthalene according to claim 1, wherein the decarboxylating agent is acetic anhydride in a molar ratio of 1 to 10 times that of ethyl 2, 3-dicyano acrylate 1G.
4. The method for synthesizing 1, 4-epoxy-2, 3-dicyano-1, 2,3, 4-tetrahydronaphthalene according to claim 3, wherein the reaction temperature is heated to reflux and acetic anhydride is added dropwise or in portions.
5. The method of claim 1, 4-epoxy-2, 3-dicyano-1, 2,3, 4-tetrahydronaphthalene synthesis, wherein the ethyl 2, 3-dicyanoacrylate 1G is prepared from ethyl 2-halo-2, 3-dicyanoacrylate 1F by elimination, according to the following reaction scheme:
wherein X ═ Cl or Br.
6. The method for synthesizing 1, 4-epoxy-2, 3-dicyano-1, 2,3, 4-tetrahydronaphthalene according to claim 5, wherein the elimination reaction uses a weak alkaline substance containing no water as a catalyst.
7. The method for synthesizing 1, 4-epoxy-2, 3-dicyano-1, 2,3, 4-tetrahydronaphthalene according to claim 6, wherein the catalyst is any one or combination of any more of triethylamine, pyridine, triethylene diamine, sodium acetate, potassium acetate and DMF.
8. The method for synthesizing 1, 4-epoxy-2, 3-dicyano-1, 2,3, 4-tetrahydronaphthalene according to claim 6, wherein the amount of the catalyst is 1 to 5 times of 1F of ethyl 2-halo-2, 3-dicyanopropionate in terms of molar ratio; in the elimination reaction, the dropping speed of the catalyst is controlled so that the liquid temperature does not exceed minus 5 ℃; after the dropwise addition is finished, the reaction is continued for 1 to 3 hours at the temperature of between 10 ℃ below zero and 5 ℃ below zero.
9. The method of claim 5, wherein ethyl 2-halo-2, 3-dicyano-1, 2,3, 4-tetrahydronaphthalene 1F is prepared from ethyl 2, 3-dicyanopropionate 1E by halogenation, according to the following reaction scheme:
10. the method of claim 9, wherein the halogenation comprises: slowly adding a halogenating reagent into an aqueous solution of 2, 3-dicyanopropionic acid ethyl ester 1E under the stirring condition of 0-10 ℃, and reacting for 1-5h, wherein the halogenating reagent is selected from the group consisting of: chlorine, bromine, hydrochloric acid and hypochlorous acid mixtures, mixtures of bromine or hydrobromic acid with any of hypobromous acid, sodium bromate and sodium perborate.
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