CN112745219A - Preparation method of 1, 1-naphthenic dicarboxylic acid and derivatives thereof - Google Patents

Preparation method of 1, 1-naphthenic dicarboxylic acid and derivatives thereof Download PDF

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CN112745219A
CN112745219A CN201911054344.XA CN201911054344A CN112745219A CN 112745219 A CN112745219 A CN 112745219A CN 201911054344 A CN201911054344 A CN 201911054344A CN 112745219 A CN112745219 A CN 112745219A
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butoxide
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魏峰
葛二鹏
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Changzhou Ruibo Bio Technology Co ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
    • C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
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    • C07C2601/14—The ring being saturated

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Abstract

The invention discloses a preparation method of 1, 1-naphthenic dicarboxylic acid and derivatives thereof, which at least comprises the following steps of forming a mixed system by malonic acid or derivatives thereof, dihalogenated hydrocarbon, tert-butoxide and a solvent in a reactor. The invention improves the conversion rate of raw materials and the selectivity of products, and hardly generates side reactions.

Description

Preparation method of 1, 1-naphthenic dicarboxylic acid and derivatives thereof
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a preparation method of 1, 1-naphthenic dicarboxylic acid and derivatives thereof.
Background
1, 1-naphthenic dicarboxylic acid and derivatives thereof are important medical intermediates. The method commonly used at present is that dibrominated hydrocarbon or dichlorohydrocarbon and malonic acid or derivatives thereof carry out twice substitution reactions under the conditions of taking potassium carbonate as alkali, taking tetrabutylammonium bromide as catalyst and taking DMF or N-methylpyrrolidone as solvent. There are, of course, some new types such as 1-butyl-3-methylimidazolium tetrafluoroborate, tetraethylammonium perchlorate, etc., which are not always favorable for conventional industrial production due to cost, procurement, etc. In the traditional method, when inorganic base is used for reaction, part of the generated water is discharged by a water separator, and the other part of the generated water is absorbed by the inorganic base to generate a crystalline hydrate, and the crystalline hydrate cannot be directly used as the base for reaction again on one hand, and on the other hand, crystal water can be removed only at a higher temperature, so that the inorganic base hydrate generated in industrial production is used as solid dangerous waste for treatment or is dried at a high temperature to remove the crystal water, so that the cost is greatly increased, and the large-scale production is not facilitated.
Disclosure of Invention
In order to overcome the disadvantages of the prior art described above, it is an object of the present invention to provide a process for producing 1-cycloalkanedicarboxylic acid and derivatives thereof, which improves the conversion of raw materials and the selectivity of products, and causes little side reaction.
In order to achieve the above objects and other objects, the present invention provides a process for producing 1, 1-cycloalkanedicarboxylic acid and derivatives thereof, which comprises the steps of,
malonic acid or a derivative thereof, dihalogenated hydrocarbon, tert-butoxide and a solvent are mixed in a reactor to form a mixed system;
and carrying out reflux reaction on the mixed system under the heating condition to obtain the 1, 1-naphthenic dicarboxylic acid and the derivative thereof, wherein the tert-butoxide promotes the removal of alpha-H of alpha carbon in the malonic acid or the derivative thereof to form the alpha carbon with substitution activity.
In one embodiment, the tert-butoxide salt is sodium tert-butoxide or potassium tert-butoxide. The molar ratio between the tert-butoxide and malonic acid or a derivative thereof is (2.1-2.5): 1.
in one embodiment, the molar ratio between the dihalohydrocarbon and the malonic acid or a derivative thereof is (1.1-1.5): 1.
in one embodiment, the molar ratio between the solvent and the malonic acid or a derivative thereof is (3-6): 1.
in one embodiment, the solvent is any one of tert-butanol, tetrahydrofuran, dioxane or toluene.
In one embodiment, the malonic acid or a derivative thereof comprises any one of malonic acid, dimethyl malonate, diethyl malonate, and monomethyl malonate.
In one embodiment, the dihalo-hydrocarbon is any one of 1, 2-dichloroethane, 1, 3-dichloropropane, 1, 4-dichlorobutane, 1, 5-dichloropentane, or 1, 2-dibromoethane, 1, 3-dibromopropane, 1, 4-dibromobutane, and 1, 5-dibromopentane.
In one embodiment, the reflux reaction time is 3 to 5 hours.
In one embodiment, the reactor is a reaction kettle.
In one embodiment, the heating condition is heating to 80-90 ℃.
In one embodiment, the 1, 1-cycloalkanedicarboxylic acids and derivatives thereof prepared in accordance with the present invention have the following structural formula:
Figure BDA0002256154240000021
in the formula: r1The radical represents H, CH3、CH2CH3；R2The radical represents H, CH3、CH2CH3。
In one embodiment, R is1Group and R2The way in which the groups are present includes: before substitution reaction, the R1Group and R2The group exists in the derivative of malonic acid or is obtained by esterification, ester exchange, hydrolysis and partial hydrolysis after ring closure reaction1Group and R2A group.
The invention can bypass the synthetic route of the generated water in the traditional method, does not need to use a catalyst, and avoids the technical difficulty brought by the use. The invention adopts tert-butoxide such as sodium tert-butoxide or potassium tert-butoxide as alkali, so that no water is generated, and the raw materials cannot be converted continuously because the water exists in the reaction system, thereby improving the conversion rate of the raw materials. Compared with the traditional method, the conversion rate of the raw materials can reach more than 99 percent, and the product yield can reach 93.4 to 97.8 percent, which is much higher than the conversion rate and the yield of the raw materials using the traditional method. The tert-butoxide is used as the base in the invention to promote the removal of alpha-H of alpha carbon in the malonic acid or the derivative thereof to form alpha carbon with substitution activity, which is beneficial to the improvement of the selectivity of a target product. The tert-butoxide has small density, is not easy to sink and is easy to stir during the reaction, the feeding amount of each batch can be correspondingly increased, and the method plays a promoting role in shortening the production period and improving the production efficiency. The traditional method needs refluxing for at least 10-24 hours, but the invention only needs refluxing for 3-5 hours, thus saving time and energy consumption and reducing cost.
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FIG. 1 is a schematic flow chart showing a process for producing 1, 1-cycloalkanedicarboxylic acid and its derivatives in one example;
FIG. 2 is a schematic diagram of an embodiment of the present invention;
FIG. 3 is a schematic diagram showing the results of gas phase detection after reaction of dimethyl malonate, 1, 2-dichloroethane, potassium tert-butoxide, and tert-butanol in a reaction kettle according to an embodiment of the present invention;
FIG. 4 is a schematic diagram showing the gas-phase detection results of dimethyl malonate, 1, 2-dibromoethane, sodium tert-butoxide and tetrahydrofuran after reaction in a reaction kettle according to another embodiment of the present invention;
FIG. 5 is a schematic diagram showing the gas-phase detection results of dimethyl malonate, 1, 5-dibromopentane, potassium tert-butoxide and dioxane after reaction in a reaction kettle according to another embodiment of the present invention;
FIG. 6 is a schematic diagram showing gas-phase detection results of diethyl malonate, 1, 3-dibromopropane, sodium tert-butoxide and tert-butanol after reaction in a reaction kettle in another embodiment of the invention.
Wherein, in fig. 2: r1Representative H, CH3、CH2CH3；R2Representative H, CH3、CH2CH3。
Detailed Description
The following description of the embodiments of the present invention is provided by way of specific examples, and other advantages and effects of the present invention will be readily apparent to those skilled in the art from the disclosure herein. The invention is capable of other and different embodiments and of being practiced or of being carried out in various ways, and its several details are capable of modification in various respects, all without departing from the spirit and scope of the present invention. It is to be noted that the features in the following embodiments and examples may be combined with each other without conflict. It is also to be understood that the terminology used in the examples is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention. Test methods in which specific conditions are not specified in the following examples are generally carried out under conventional conditions or under conditions recommended by the respective manufacturers.
When numerical ranges are given in the examples, it is understood that both endpoints of each of the numerical ranges and any value therebetween can be selected unless the invention otherwise indicated. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs and the description of the present invention, and any methods, apparatuses, and materials similar or equivalent to those described in the examples of the present invention may be used to practice the present invention.
The method bypasses the synthetic route of the traditional method, so that the yield and the selectivity of the product are improved, and the tert-butoxide is used as the base in the method to promote the removal of alpha-H of alpha carbon in the malonic acid or the derivative thereof to form alpha carbon with substitution activity, thereby being beneficial to the improvement of the selectivity of a target product.
As shown in fig. 1, an embodiment of the present invention provides a method for preparing 1, 1-cycloalkanedicarboxylic acid and derivatives thereof, comprising the steps of:
s1, forming a mixed system by malonic acid or a derivative thereof, dihalogenated hydrocarbon, tert-butoxide and a solvent in a reactor;
s2, carrying out reflux reaction on the mixed system under the heating condition to obtain the 1, 1-naphthenic dicarboxylic acid and the derivative thereof, wherein the tert-butoxide promotes the elimination of alpha-H of alpha carbon in the malonic acid or the derivative thereof to form the alpha carbon with substitution activity.
Specifically, in step S1, the malonic acid or a derivative thereof includes any one of malonic acid, dimethyl malonate, diethyl malonate, and monomethyl malonate. The dihalogenated hydrocarbon is any one of 1, 2-dichloroethane, 1, 3-dichloropropane, 1, 4-dichlorobutane, 1, 5-dichloropentane or 1, 2-dibromoethane, 1, 3-dibromopropane, 1, 4-dibromobutane and 1, 5-dibromopentane.
The tert-butoxide is sodium tert-butoxide or potassium tert-butoxide. The molar ratio between the tert-butoxide and malonic acid or a derivative thereof is (2.1-2.5): 1. the molar ratio between the dihalohydrocarbon and the malonic acid or a derivative thereof is (1.1 to 1.5): 1. the molar ratio between the solvent and the malonic acid or a derivative thereof is (3-6): 1. the solvent is any one of tert-butyl alcohol, tetrahydrofuran, dioxane or toluene. The reactor is for example a reaction kettle. The structural formulas of the sodium tert-butoxide and the potassium tert-butoxide are respectively as follows:
Figure BDA0002256154240000041
specifically, in step S2, the reflux reaction of the mixed system under heating condition includes: heating to 80-90 ℃, and carrying out reflux reaction for 3-5 hours. After the reflux reaction is finished, some surface treatment steps are also included, for example, after the reflux reaction is finished, the reaction product is cooled to room temperature, part of undissolved tert-butoxide and generated chloride salt or bromide salt are removed by suction filtration, the tert-butanol is distilled off under reduced pressure, then water and dichloromethane are added for layering to obtain an organic layer, the organic layer is washed once by saturated common salt water, and the dichloromethane is distilled off under reduced pressure to obtain the 1, 1-naphthenic dicarboxylic acid and derivatives thereof. Other derivatives operate similarly except for the corresponding substrates.
The invention also provides structural formulas of the 1, 1-naphthenic dicarboxylic acid and the derivative thereof, wherein the structural formulas are as follows:
Figure BDA0002256154240000042
in the formula: r1The radical represents H, CH3、CH2CH3；R2The radical represents H, CH3、CH2CH3. Wherein R is1Radical, R2The group can be present in a derivative of malonic acid before substitution reaction, or can be prepared by esterification reaction, ester exchange reaction, hydrolysis reaction, partial hydrolysis and other reactions after ring closure reaction, and the route is determined according to actual conditions.
In one embodiment, 132g (1mol) of dimethyl malonate, 108.9g (1.1mol) of 1, 2-dichloroethane, 246.4g (2.2mol) of potassium tert-butoxide and 528ml of tert-butanol are added into a reaction kettle, the mixture is heated to 80-90 ℃, reflux reaction is carried out for 3-5 hours, the mixture is cooled to room temperature, part of undissolved potassium tert-butoxide and generated potassium chloride are removed by suction filtration, the tert-butanol is removed by reduced pressure evaporation, 260ml of water and 260ml of dichloromethane are added, layering is carried out, an organic layer is washed by 260ml of saturated common salt once, the dichloromethane is removed by reduced pressure distillation, 147.5g of the product is obtained, and the yield is 93.4%. And GC content detection: 99.66%, see in particular the gas phase detection results of fig. 3.
Nuclear magnetic data:1H NMR(400MHz，CDCl3)δppm：3.65(t，J＝4.2Hz，6H)，1.37(t，J＝4.8Hz，4H)。
the reaction relation is as follows:
Figure BDA0002256154240000051
in another embodiment, 132g (1mol) of dimethyl malonate, 206.8g (1.1mol) of 1, 2-dibromoethane, 211.2(2.2mol) of sodium tert-butoxide and 528ml of tetrahydrofuran are added into a reaction kettle, the mixture is heated to 80-90 ℃, refluxed and reacted for 3-5 hours, cooled to room temperature, filtered to remove part of undissolved sodium tert-butoxide and generated sodium bromide by suction, evaporated to remove tetrahydrofuran by reduced pressure, added with 260ml of water and 260ml of dichloromethane, layered, washed with 260ml of saturated common salt for one time, and distilled to remove dichloromethane by reduced pressure, thus obtaining 150.3g of the product with the yield of 95.1%. And GC content detection: 99.67%, see in particular the gas phase detection results of fig. 4.
The reaction of this example is as follows:
Figure BDA0002256154240000052
nuclear magnetic data:1H NMR(400MHz，CDCl3)δppm：3.64(t，J＝4.2Hz，6H)，1.39(t，J＝4.8Hz，4H)。
in another embodiment, 132g (1mol) of dimethyl malonate, 276g (1.2mol) of 1, 5-dibromopentane, 246.4(2.2mol) of potassium tert-butoxide and 528ml of dioxane are added into a reaction kettle, the mixture is heated to 80-90 ℃, reflux reaction is carried out for 3-5 hours, the mixture is cooled to room temperature, part of undissolved potassium tert-butoxide and generated potassium bromide are removed by suction filtration, dioxane is removed by reduced pressure evaporation, 260ml of water and 260ml of dichloromethane are added, layering is carried out, an organic layer is washed by 260ml of saturated common salt and dichloromethane is removed by reduced pressure distillation, 195.6g of a product is obtained, and the yield is 97.8%. And GC content detection: 99.48%, see in particular the gas phase detection results of fig. 5.
The reaction of this example is as follows:
Figure BDA0002256154240000061
nuclear magnetic data:1H NMR(400MHz，CDCl3)δppm：1.5(m，6H)，2.0(m，4H)，3.7(s，6H)。
in another example, 104g (1mol) of malonic acid, 254g (1.1mol) of 1, 4-dichlorobutane, 459.2g (4.1mol) of potassium tert-butoxide and 416ml of toluene are added into a reaction kettle, the temperature is raised to 80-90 ℃, reflux reaction is carried out for 3-5 hours, the mixture is cooled to room temperature, the solvent is removed by suction filtration, 260ml of water is added, the pH value is adjusted to 1.0 by hydrochloric acid, and the product is precipitated, so that 148.4g of solid is obtained, wherein the yield is 93.9%. The content is 99.35% according to the potentiometric titration detection of a sodium hydroxide standard solution (in the substrate, 2 times more alkali is needed to ensure that a reaction system is alkaline because malonic acid is acidic, and corresponding adjustment is correspondingly made in the post-treatment).
The reaction of this example is as follows:
Figure BDA0002256154240000062
nuclear magnetic data:1H NMR(400MHz，DMSO-d6)δppm：2.05–1.99(m，4H)，1.60–1.54(m，4H)。
in another embodiment, 160g (1mol) of diethyl malonate, 222.2g (1.1mol) of 1, 3-dibromopropane, 211.2(2.2mol) of sodium tert-butoxide and 640ml of tert-butanol are added into a reaction kettle, the mixture is heated to 80-90 ℃, reflux reaction is carried out for 3-5 hours, the mixture is cooled to room temperature, part of undissolved sodium tert-butoxide and generated sodium bromide are removed by suction filtration, the tert-butanol is removed by reduced pressure evaporation, 260ml of water and 260ml of dichloromethane are added, layering is carried out, an organic layer is washed by 260ml of saturated common salt water, the dichloromethane is removed by reduced pressure distillation, 191g of the product is obtained, and the yield is 95.5%. And GC content detection: 99.22%, see in particular the gas phase test results of FIG. 6.
The reaction of this example is as follows:
Figure BDA0002256154240000063
nuclear magnetic data: 1H NMR (400MHz, CDCl3) delta ppm: 4.20(q, 4H), 2.55(t, 4H), 1.98(q, 2H), 1.25(t, 6H).
In the traditional synthesis method, the removed hydrogen bromide or hydrogen chloride can be subjected to neutralization reaction with alkali reagents such as potassium carbonate, sodium carbonate, potassium bicarbonate and the like to generate water. The adverse factor of water in the reaction, and the invention can bypass the route and use sodium tert-butoxide or potassium tert-butoxide as base, so that no water is generatedThe conversion rate of the raw material is improved because the raw material cannot be converted continuously because moisture exists in the reaction system all the time. Compared with the traditional method, the method has the advantages that the conversion rate of raw materials and the yield of products are greatly improved. Because of the strong activity of potassium tert-butoxide or sodium tert-butoxide, when three-or four-membered rings are formed, the reaction rate of dibromohydrocarbon has no obvious advantage over dichlorohydrocarbon, so that dichlorohydrocarbon is generally adopted in consideration of reaction activity and cost. The strong activity of the alkali reagent is beneficial to the removal of the 1, 1-naphthenic dicarboxylic acid and the derivative alpha-H thereof to generate carbanions, the improvement of the conversion rate of raw materials is facilitated, the reaction time is shortened, meanwhile, the probability of side reaction is reduced, the volatilization loss of corresponding dihalogenated hydrocarbon is less, the amount of dihalogenated hydrocarbon of the method is less, and can be reduced to 1.1-1.5 times of the molar amount of the 1, 1-naphthenic dicarboxylic acid and the derivative thereof, the usage amount of the dihalogenated hydrocarbon is greatly reduced, the aftertreatment pressure can also be reduced, and the residue of the dihalogenated hydrocarbon is easy to control in a relatively low range. In the traditional method, the density of the used potassium carbonate is 2.43g/cm3The density of the potassium bicarbonate is 2.17g/cm3The density of the sodium carbonate is 2.53g/cm3And potassium tert-butoxide is 0.92g/cm3Sodium tert-butoxide 1.10g/cm3The density is much lower than that of inorganic bases such as potassium carbonate, sodium carbonate and potassium hydrogen carbonate, that is, the reaction does not easily settle down like inorganic bases and is difficult to stir. The feeding amount of each batch can be correspondingly increased, and the method plays a promoting role in shortening the production period and improving the production efficiency. After the reaction is finished, slightly excessive potassium tert-butoxide and sodium tert-butoxide can be replenished after the suction filtration and separation and continuously put into the next batch of production, and compared with the inorganic base used in the traditional method, the method reduces the treatment cost of wastes. Meanwhile, the invention can obtain the conversion rate of more than 99 percent without using a catalyst, and in the actual production, the invention not only reduces the post-treatment pressure, but also reduces the cost. As inorganic base is used to continuously generate a large amount of water in the traditional method, on one hand, the water needs to be separated as soon as possible, and on the other hand, tetrabutylammonium bromide, tetrabutylammonium chloride, PEG400, 18-crown-6 and other phase transfer catalysts are added to promote the reactionShould be used. The tetrabutylammonium bromide and the tetrabutylammonium chloride can be largely decomposed at 105-110 ℃ to generate tributylamine and the like, and meanwhile, the risk is high in production along with rapid heat release; meanwhile, tetrabutylammonium bromide, tetrabutylammonium chloride and PEG400 have good solubility in water and organic solvents and are difficult to remove; the 18-crown-6 has higher cost and is not suitable for industrial production, but the invention does not need to use a catalyst, avoids a series of disadvantages caused by using the catalyst and simultaneously improves the selectivity and the yield of a target product. In the traditional method, the reaction time is long, the intermolecular substitution reaction can occur with other unreacted malonic acid or other derivative molecules by combining other factors, and the product has similar physical and chemical properties with the product, so once the byproduct is generated, the separation is difficult. The general idea is to shorten the reaction time, so as to separate out pure products and to leave out the byproducts, and to take the right choice for the reaction conditions and the conversion degree of the raw materials, which causes a contradiction, or the raw materials have low conversion rate, and the raw materials can be removed only by purification for many times, or the byproducts are already generated, at this time, only the reaction can be stopped for purification, but the method of the present invention has almost no byproducts.
Furthermore, it is to be understood that one or more method steps mentioned in the present invention does not exclude that other method steps may also be present before or after the combined steps or that other method steps may also be inserted between these explicitly mentioned steps, unless otherwise indicated; it is also to be understood that a combined connection between one or more devices/apparatus as referred to in the present application does not exclude that further devices/apparatus may be present before or after the combined device/apparatus or that further devices/apparatus may be interposed between two devices/apparatus explicitly referred to, unless otherwise indicated. Moreover, unless otherwise indicated, the numbering of the various method steps is merely a convenient tool for identifying the various method steps, and is not intended to limit the order in which the method steps are arranged or the scope of the invention in which the invention may be practiced, and changes or modifications in the relative relationship may be made without substantially changing the technical content.
The foregoing embodiments are merely illustrative of the principles and utilities of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or change the above-mentioned embodiments without departing from the spirit and scope of the present invention. Accordingly, it is intended that all equivalent modifications or changes which can be made by those skilled in the art without departing from the spirit and technical spirit of the present invention be covered by the claims of the present invention.

Claims (10)

1. A process for the preparation of 1, 1-cycloalkanedicarboxylic acids and derivatives thereof, comprising at least the steps of,
malonic acid or a derivative thereof, dihalogenated hydrocarbon, tert-butoxide and a solvent are mixed in a reactor to form a mixed system;
and carrying out reflux reaction on the mixed system under the heating condition to obtain the 1, 1-naphthenic dicarboxylic acid and the derivative thereof, wherein the tert-butoxide promotes the removal of alpha-H of alpha carbon in the malonic acid or the derivative thereof to form the alpha carbon with substitution activity.
2. The production method according to claim 1, wherein the tert-butoxide is sodium tert-butoxide or potassium tert-butoxide.
3. The production method according to claim 1, wherein the molar ratio between the tert-butoxide and the malonic acid or a derivative thereof is (2.1 to 2.5): 1.
4. the production method according to claim 1, characterized in that the molar ratio between the dihalohydrocarbon and the malonic acid or a derivative thereof is (1.1-1.5): 1.
5. the method according to claim 1, wherein the solvent is any one of tert-butanol, tetrahydrofuran, dioxane, and toluene.
6. The method according to claim 1, wherein the malonic acid or a derivative thereof is any one of malonic acid, dimethyl malonate, diethyl malonate, and monomethyl malonate.
7. The production method according to claim 1, wherein the dihalo-hydrocarbon is any one of 1, 2-dichloroethane, 1, 3-dichloropropane, 1, 4-dichlorobutane, 1, 5-dichloropentane, or 1, 2-dibromoethane, 1, 3-dibromopropane, 1, 4-dibromobutane, and 1, 5-dibromopentane.
8. The method according to claim 1, wherein the reflux reaction is carried out for 3 to 5 hours.
9. The method of claim 1, wherein the reactor is a reaction kettle.
10. The method according to claim 1, wherein the heating condition is heating to 80 to 90 ℃.
CN201911054344.XA 2019-10-31 2019-10-31 Preparation method of 1, 1-naphthenic dicarboxylic acid and derivatives thereof Pending CN112745219A (en)

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