JP2007153757A - Method for producing 1,2-diarylamino-1,2-ethylenedicarboxylic acid alkyl ester - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing a 1,2-diarylamino-1,2-ethylenedicarboxylic acid alkyl ester in a high yield and in high productivity. <P>SOLUTION: The method for producing a 1,2-diarylamino-1,2-ethylenedicarboxylic acid alkyl ester comprises using an alkali metal carbonate as a basic catalyst in an equivalent higher than that of a hydrogen halide formed, obtaining an anilinoacetic acid alkyl ester compound in an anhydrous alcohol as an organic solvent and carrying out each reaction process until the production of a final product in the same reaction apparatus without purifying a reaction mixture of each subsequent process after the production of the anilinoacetic acid alkyl ester compound. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a method for producing a 1,2-diarylamino-1,2-ethylenedicarboxylic acid alkyl ester having high yield and high productivity.

  Quinonoquinolone compounds exhibit yellow to orange color and are excellent in various durability such as light resistance and solvent resistance. It has been proposed to be used for special applications such as organic electroluminescence devices (Patent Documents 1, 2, or 3).

  Such a quinolonoquinolone compound was synthesized for the first time in 1948 with a parent skeleton. Regarding this compound, Non-Patent Document 1 is known, in which dimethoxy, diethoxy substituted products and di, tri, and tetrahalogen substituted products are described as pigments excellent in light resistance and coloring power. Such a quinolonoquinolone compound is originally produced by cyclizing 1,2-diarylamino-1,2-ethylenedicarboxylic acid alkyl ester (Non-patent Document 1). In addition, Non-Patent Document 2 is also known.

  It is known that 1,2-diarylamino-1,2-ethylenedicarboxylic acid alkyl ester is produced mainly by two production methods (Patent Documents 1 and 2). One is a method of performing esterification of dihydroxyfumaric acid and dehydration condensation with aniline or substituted aniline (first method), and the other is N-phenyl which may have a substituent on the benzene ring. A process for producing an oxalic acid diester substituted with a phenylamino group which may have a substituent on the benzene ring from an ester of glycine and an oxalic acid diester, and reacting this with aniline or substituted aniline (second method) Method).

  However, these production reactions may be low in reaction rate or may easily generate by-products, and are taken out from the reaction vessel and purified in each reaction step. , 2-diarylamino-1,2-ethylenedicarboxylic acid alkyl ester has a disadvantage that the yield is low and the productivity per unit time is lowered.

  If the series of reactions as described above are carried out in a single reaction apparatus, the disadvantages as described above are likely to be solved to some extent, but alkyl 1,2-diarylamino-1,2-ethylenedicarboxylate. No specific means for producing an ester with high yield and high productivity is provided from these documents.

Japanese Patent Laid-Open No. 10-17783 Japanese Patent Laid-Open No. 11-80576 JP-A-11-130972 Helv. Chim. Acta, 31, 716 J. et al. Heterocyclic Chem, 16, 1651 (1979)

  The problem to be solved by the present invention is to provide a method for producing a 1,2-diarylamino-1,2-ethylenedicarboxylic acid alkyl ester with high yield and high productivity.

  The present inventors diligently studied a suitable production method for producing a 1,2-diarylamino-1,2-ethylenedicarboxylic acid alkyl ester with high yield and high productivity, and found that the reaction mixture of each step It is found that the above-mentioned problems can be solved by conducting the reaction in a system with as little water as possible by focusing on the amount of the reaction catalyst and the solvent, and performing them in the same reactor without purification. The present invention has been completed.

That is, the present invention provides the following inventions.
In the process for producing 1,2-diarylamino-1,2-ethylenedicarboxylic acid alkyl ester comprising the following steps:
Performing step 1 in an anhydrous alcohol as an organic solvent, using an alkali metal carbonate as a basic catalyst in the following step 1 in an amount larger than the hydrogen halide to be produced,
The following steps 1 to 4 are performed in the same reactor without purifying the reaction mixture in each step.
A process for producing a 1,2-diarylamino-1,2-ethylenedicarboxylic acid alkyl ester, characterized in that
Step 1: An aniline compound and a halogenoacetic acid alkyl ester compound are dehydrohalogenated in an organic solvent in the presence of a basic catalyst to obtain an anilinoacetic acid alkyl ester compound.
Step 2: The reaction product is obtained by subjecting the anilinoacetic acid alkyl ester compound and oxalic acid di-lower alkyl ester compound to a nucleophilic substitution reaction.
Step 3: The reaction product is hydrolyzed with an acid to obtain an intermediate.
Step 4: The intermediate is reacted with an aniline compound to obtain a 1,2-diarylamino-1,2-ethylenedicarboxylic acid alkyl ester.

  In the production method of the present invention, the reaction mixture in each step is not purified in the same reaction apparatus, and the reaction is performed in a system with as little water as possible by focusing on the amount of the reaction catalyst and the solvent. Therefore, the 1,2-diarylamino-1,2-ethylenedicarboxylic acid alkyl ester can be produced with a high yield and high productivity.

Next, the present invention will be described in detail.
In the production method described above, the present invention is carried out in the same reaction apparatus in all steps and by selecting the amount of reaction catalyst and the solvent used. Each process itself is a known and commonly used process. Each step is shown by the reaction formula as follows.

Step 1:

Step 2:

Step 3:

Step 4:

In the chemical formula of each process, R 1 _a and R _{1 b} are may be the same or different hydrogen atom, a lower alkyl group or a halogen atom, in the 2-position and 6-position of the benzene ring R _{1 a} and R ₁ b And R ₁ a and R ₁ b are not both hydrogen atoms. The lower alkyl group refers to an alkyl group having 1 to 3 carbon atoms. R _{2 to} R ₄ are lower alkyl groups, X is a halogen atom, and M is an alkali metal. R _{5 to} R ₆ are alkyl groups having 1 to 5 carbon atoms. Each alkyl group of R _{1 to} R ₆ may have the same number of carbon atoms.

  In step 1, the aniline compound (A) and the halogenoacetic acid alkyl ester compound (B) are dehydrohalogenated in an organic solvent in the presence of a basic catalyst to give the anilinoacetic acid alkyl ester compound (C). It is a process to obtain. The aniline compound (A) and the halogenoacetic acid alkyl ester compound (B) may be reacted using, for example, the same or substantially the same number of moles.

  Here, the aniline compound (A) means aniline and aniline substituted with a lower alkyl group or a halogen atom. Examples of the lower alkyl group include a methyl group, an ethyl group, and an iso-propyl group. Examples of the halogen atom include a chlorine atom and a bromine atom. Examples of the aniline compound (A) include aniline, o-toluidine, p-toluidine, p-ethylaniline, p-iso-propylaniline, p-chloroaniline, monosubstituted anilines such as p-bromoaniline, 2, 3 -Xylidine, 3,4-xylidine, 2,4-dichloroaniline, 2,4,5-trimethylaniline.

  Examples of the halogenoacetic acid alkyl ester compound (B) include ethyl chloroacetate, methyl chloroacetate, ethyl bromoacetate, and methyl bromoacetate.

  The anilinoacetic acid alkyl ester compound (C) can be easily obtained by dehydrohalogenating the aniline compound (A) with the halogenoacetic acid alkyl ester compound (B). The hydrogen halide generated by the reaction varies depending on the compound (B) used, and is, for example, hydrogen chloride, hydrogen bromide or the like.

In the present invention, the dehydrohalogenation reaction in Step 1 is carried out in an organic solvent in the presence of a basic catalyst. At this time, an alkali metal carbonate is used as the basic catalyst. Examples of the alkali metal carbonate include sodium carbonate, potassium carbonate, lithium carbonate and the like. These are preferably not hydrated salts. In the present invention, anhydrous alcohol is used as the organic solvent. Examples of the alcohol include monoalcohols having 1 to 6 carbon atoms such as methanol, ethanol, iso-propanol, tert-butanol, and tert-amyl alcohol. The alcohol used in the present invention is anhydrous alcohol. Anhydrous means that the water content is less than 100 ppm. From the viewpoint of easy reaction control and easy concentration, the alcohol is preferably used in the same amount to 4 times the amount as the raw material.

  In the dehydrohalogenation reaction, theoretically, an equimolar number of hydrogen halides is generated from the number of moles of the compound (B). The present invention is characterized in that the alkali metal carbonate having an equivalent number larger than the theoretical amount of hydrogen halide that can be produced in Step 1 is used. That is, it is preferable to use an alkali metal carbonate having a mole number equal to or greater than the number of moles of the compound (B), in particular, an alkali metal carbonate having a mole number of 1 to 1.5 times the mole number of the compound (B). . By carrying out like this, a compound (C) is obtained with a high yield, keeping a reaction system alkaline. By doing so, it is possible to prevent the formation of carbonic acid and, as a result, water which is a decomposition product thereof. In the present invention, since anhydrous alcohol is used as a solvent, the liquidity in the system cannot be expressed by pH, but as described above, the alkali metal carbonate having an equivalent number larger than the theoretical amount of hydrogen halide that can be produced. Therefore, it is theoretically impossible that the reaction system becomes acidic, including weak acidity, even if it is assumed to be an aqueous system. In Step 2 to be described later, since the reaction is carried out in an anhydrous system using an alkali metal alkoxide, it is extremely important that there is no room for water to be generated in this Step 1 due to the raw material or the reaction. .

  Step 1 can be performed at a predetermined reaction temperature and reaction time under stirring. The reaction conditions are not particularly limited as long as the compound (C) is generated. For example, the reaction can be performed at a temperature of 70 to 100 ° C. for 8 to 40 hours. When the solvent is a low-boiling point alcohol, the reaction may be performed in a closed system. The reaction is preferably performed in an inert gas atmosphere such as nitrogen or a noble gas. The end point of the reaction can be confirmed by, for example, disappearance of the compound (B) raw material peak at a predetermined retention time in gas chromatography by sampling. If it is determined that the end point has been reached, the reaction temperature is preferably lowered toward room temperature.

  Step 2 is a step of obtaining a reaction product (E) by subjecting the anilinoacetic acid alkyl ester compound (C) produced in Step 1 to a nucleophilic substitution reaction with the oxalic acid di-lower alkyl ester compound (D).

  Examples of the oxalic acid di-lower alkyl ester compound (D) include dimethyl oxalate, diethyl oxalate, and diisopropyl oxalate.

  In Step 2, for example, the compound (D) is further charged into the reaction apparatus in which the reaction in Step 1 has been completed. Since the reaction for obtaining the reactive product (E) from the compound (C) obtained in step 1 and this compound (D) is theoretically an equimolar reaction, both are the same or substantially the same number of moles. The compound (D) may be charged so that That is, it is preferable to use the compound (D) having a number of moles equal to or greater than the number of moles of the compound (C), in particular, 1 to 1.8 times the number of moles of the compound (C). However, when the actual number of moles of the compound (C) formed is unknown, the number of moles of the compound (B) in Step 1 may be the same or substantially the same number of moles based on the number of moles charged. .

  The nucleophilic substitution reaction in Step 2 can be performed by drawing active hydrogen on the carbon atom at the α-position of the nitrogen atom of the compound (C) with a basic catalyst and reacting the site with the compound (D). I can do it. As the basic catalyst at this time, it is preferable to use an alkali metal alkoxide instead of the catalyst suitably used in Step 1. This is because the reaction in an anhydrous system using an alkali metal alkoxide can be completed more reliably.

  Examples of the alkali metal alkoxide include lithium methoxide, sodium methoxide, sodium ethoxide, sodium iso-propoxide, sodium tert-butoxide, sodium tert-pentoxide (sodium-2-methyl-2-butoxide) and the like. Can be used. The alkali metal alkoxide can be easily obtained by reacting an alkali metal such as lithium or sodium with a monoalcohol. In the present invention, since anhydrous alcohol is used in the step 1, an alkali metal alkoxide can be prepared by mixing this with a necessary alkali metal.

  The alkali metal alkoxide may be used so as to have the same number of moles or more as that of the compound (D), but among them, it is preferable to use a number of moles 1 to 1.8 times the number of moles of the compound (D).

  In this step 2, it is preferable to mix the reaction mixture of step 1 and an alkali alcohol alkoxide solution prepared in advance. In the mixing of the reaction mixture of Step 1 and the previously prepared alkali metal alkoxide in anhydrous alcohol solution, the alkali metal alkoxide in anhydrous alcohol solution is preferably added to the stirring Step 1 reaction mixture. In this case as well, it is preferable to cool the reaction mixture in advance and then add an anhydrous alcohol solution of an alkali metal alkoxide. The alcohol solution may be added all at once, but is preferably added dropwise to facilitate reaction control.

  This reaction is preferably performed at -20 to + 20 ° C, preferably -10 ° C to + 10 ° C. For cooling, for example, an appropriate amount of refrigerant such as ice or a mixture of salt and ice can be used. The reaction can be carried out over 6 to 30 hours after adding the total amount of the alkali metal alkoxide in anhydrous alcohol. In order to ensure safety, at the initial stage of the reaction, the reaction is carried out while maintaining the temperature on the lower temperature side in the temperature range described above, and when the reaction rate approaches saturation, the temperature is increased to a higher temperature side in the temperature range described above. The reaction can be carried out by holding. This step 2 is also preferably performed in an inert gas atmosphere. The end point of the reaction can be confirmed, for example, by disappearance of the compound (C) raw material peak at a predetermined retention time in high performance liquid chromatography by sampling.

  Step 3 is a step in which the reaction product (E) obtained in Step 2 is hydrolyzed with an acid to obtain an intermediate. In this step, the reaction product that is an alkali metal salt is used as the intermediate (F). This hydrolysis can be performed by mixing the reaction product obtained in Step 2 and an acid.

  Examples of the acid include hydrogen chloride, hydrogen bromide, sulfuric acid, phosphoric acid, acetic acid, and the like, but the neutralized salt produced in this step can be made into water-soluble and non-toxic sodium chloride. Hydrogen is preferred. Hydrogen chloride may be used so as to be equal to or greater than the total number of moles of the remaining alkali metal carbonate in Step 1 and the hydrogen carbonate metal salt that can be formed and the alkali metal alkoxide in Step 2, but among them, the total number of moles of both. It is preferable to use it so that it may become 1 to 1.8 times the number of moles.

  The acid may be a gas or an aqueous solution. When hydrogen chloride gas is used as the acid, the reaction product obtained in step 2 may be bubbled, and when an aqueous solution is used, the reaction product obtained in step 2 and hydrogen chloride are used. The aqueous solution may be mixed. However, it is preferable that the hydrogen chloride is an aqueous solution in that the exhaust gas treatment is unnecessary and handling is easier. An aqueous solution of hydrogen chloride is easily available as, for example, hydrochloric acid. In the mixing of the reaction product of Step 2 and an aqueous solution of hydrogen chloride, an aqueous solution such as hydrochloric acid is preferably added to the stirring reaction product of Step 2. Also in this case, it is preferable to cool the reaction product in advance and then add an aqueous solution of hydrogen chloride. This aqueous solution may be added all at once, but is preferably added dropwise in order to suppress heat generation.

  This reaction is also preferably performed in the same temperature range as in step 2. If necessary, the various refrigerants described above can be used. The reaction can be carried out for an additional 3 to 15 hours after adding the total amount of hydrogen chloride. Similar to step 2, the temperature can be changed stepwise. As a result of the alkali metal carbonate and alkali metal alkoxide used in Steps 1 and 2 being sufficiently neutralized with hydrogen chloride, Step 3 is finally neutral to acidic. The end point of the reaction can be confirmed by, for example, the reaction mixture containing an intermediate having a desired pH of 2.5 to 3.0 by sampling and no change in pH value.

  Step 4 is a step of obtaining 1,2-diarylamino-1,2-ethylenedicarboxylic acid alkyl ester (G) by reacting intermediate (F) with aniline compound (A). The 1,2-diarylamino-1,2-ethylenedicarboxylic acid alkyl ester is the name of a compound named with the carbon atom forming the ethylenically unsaturated double bond as the 1-position and 2-position. In Step 1 and Step 4, both aniline compounds having the same structure and aniline compounds having structures different from each other can be used. The intermediate (F) in step 3 and the aniline compound (A) may be reacted using, for example, the same or substantially the same number of moles.

  The ester (G) can be easily obtained by subjecting the intermediate (F) and the aniline compound (A) to a dehydration condensation reaction. The reaction system of step 4 through steps 1 to 3 mainly includes alcohol and water as solvents. Also, when hydrochloric acid is used as the acid in step 3, it is acidic based on hydrogen chloride. In the reaction system, the dehydration condensation can be performed by refluxing.

  Examples of the ester (G) produced in Step 4 include dimethyl dianilino maleate, dimethyl dianilinofumarate, dimethyl ditoluidino maleate, dimethyl ditoluidino fumarate, dimethyl di (chloroanilino) maleate, and di (chloroanilino). Examples include dimethyl fumarate, diisopropyl dianilino maleate, diisopropyl dianilinofumarate, diisopropyl ditoluidino maleate, diisopropyl ditoluidino fumarate, diisopropyl di (chloroanilino) maleate, diisopropyl di (chloroanilino) fumarate, and the like.

  The ester (G) produced in step 4 may be a diarylaminomaleic acid dialkyl ester as described above, a diarylaminofumaric acid dialkyl ester as described above, or a mixture thereof. Usually, it is a mixture of the two geometric isomers.

  Step 4 can be performed at a predetermined reaction temperature and reaction time under stirring. The reaction conditions are not particularly limited as long as the ester (G) is generated. For example, the reaction can be performed at a temperature of 70 to 95 ° C. for 2 to 10 hours. If necessary, water may be further added to complete the reaction. The end point of the reaction can be confirmed, for example, by maximizing the peak of the product ester (G) at a predetermined retention time in high performance liquid chromatography by sampling. If it is determined that the end point has been reached, the reaction temperature is preferably lowered toward room temperature.

  In the present invention, each step is carried out in the same reaction apparatus without being once taken out or purified after each step, and in the initial reaction of steps 1 and 2, the amount of the reaction catalyst is set within a specific range and anhydrous. Therefore, it is possible to minimize the yield and decrease the productivity per unit time. Compared to the method in which steps 2 to 4 are all carried out in the same reactor, the method of the present invention in which all steps 1 to 4 are carried out in the same reactor, There is little trouble of preparation, etc., yield can be increased, and productivity per unit time is also high.

  Thus, the reaction mixture containing the ester (G) produced in Step 4 can be purified by cooling, filtering, washing and re-filtering in order to reduce the solubility in the solvent as much as possible. The wet cake thus obtained can be used as it is for known and commonly used applications. The wet cake can be used for known and commonly used applications as granules and powders by further drying and grinding.

  The ester (G) thus obtained can be converted to a quinolonoquinolone compound by cyclization.

  The ester (G) may be subjected to two cyclization reactions at a time, but it is difficult. First, in an aromatic or aliphatic organic solvent having a boiling point of 180 to 300 ° C. at normal temperature, the first ring It is preferable to remove the organic solvent, and then perform the second cyclization reaction in various inorganic acids such as polyphosphoric acid at 80 to 200 ° C. to remove the inorganic acid.

  Thus, the obtained quinolonoquinolone compound can be purified by washing and filtering again. The wet cake thus obtained can be used as it is for known and commonly used organic pigments. The wet cake can be used for known and commonly used applications as granules and powders by further drying and grinding.

  Next, the present invention will be described in detail with reference to examples. Hereinafter, unless otherwise specified, both parts and% are based on mass.

Step 1:
A reactor was charged with 21.5 parts of p-toluidine, 24.5 parts of ethyl chloroacetate, 26.5 parts of sodium carbonate and 80 parts of dehydrated ethanol, and reacted at 78 ° C. for 20 hours with stirring in a nitrogen atmosphere. Until the ester (C1) was produced.

Step 2:
While stirring the reaction mixture of Step 1 described above, 40.8 parts of diethyl oxalate was further added and cooled to −5 ° C., and a mixed solution of 19.1 parts of sodium ethoxide and 130 parts of dehydrated ethanol was added for 2 hours. It was dripped at. Thereafter, stirring was continued at 5 ° C. or lower for 8 hours at room temperature for 12 hours to generate an addition reaction product (E1).

Step 3:
While the reaction mixture of Step 2 was cooled to -5 ° C again, 60.5 parts of 35% hydrochloric acid was added dropwise over 4 hours to the mixture with stirring. Thereafter, stirring was continued at 10 ° C. or lower, 5 hours, room temperature, and 12 hours to produce an intermediate (F1).

Step 4:
30.0 parts of p-toluidine was further added while stirring the reaction mixture of Step 3 described above, and then refluxed at 80 to 81 ° C. for 6 hours to produce an ester (G1).

  Further, the reaction mixture of Step 4 was allowed to stand overnight at room temperature, then cooled to 0 ° C., filtered, washed and dried to obtain 43.7 parts of a powder that was considered to be ester (G1). This was found to be diethyl 1,2-ditoludino-1,2-ethylenedicarboxylate from a molecular ion peak by mass spectrometry.

  Further, this powder was found to be a mixture of diethyl di-p-toluidinomaleate and diethyl di-p-toluidinofumarate from the retention time of the standard substance by high performance liquid chromatography (HPLC). The yield and purity of diethyl 1,2-ditoludino-1,2-ethylenedicarboxylate based on the HPLC area ratio were 56.5% and 97%, respectively.

Step 1:
Using 18.6 parts of aniline instead of 21.5 parts of p-toluidine, and performing the same operation as in step 1 of Example 1 except that the reaction time is set to 31 hours, an ester (C2) is produced. I let you.

Step 2:
While stirring the reaction mixture of Step 1 described above, 40.8 parts of diethyl oxalate was further added and cooled to 0 ° C., and a mixed solution of 19.1 parts of sodium ethoxide and 130 parts of dehydrated ethanol was added over 4 hours. It was dripped. Thereafter, stirring was continued at room temperature for 24 hours to produce an addition reaction product (E2).

Step 3:
While the reaction mixture in Step 2 was cooled to 0 ° C. again, 60.5 parts of 35% hydrochloric acid was added dropwise to the mixture with stirring over 4 hours. Thereafter, stirring was continued at 10 ° C. or lower for 5 hours at room temperature for 12 hours to produce an intermediate (F2).

Step 4:
26.0 parts of aniline was further added under stirring of the reaction mixture in Step 3 described above, and then refluxed at 80 to 81 ° C. for 6 hours to produce an ester (G2).

  Further, the reaction mixture of Step 4 was left overnight at room temperature, 200 parts of water was added, and 100 parts of a mixture of ethanol and water was distilled off. Next, after cooling to 5 ° C., filtration, washing, and drying, 39.7 parts of a powder thought to be ester (G2) was obtained. This was found to be diethyl 1,2-dianilino-1,2-ethylenedicarboxylate from a molecular ion peak by mass spectrometry.

  Further, this powder was found to be a mixture of diethyl dianilino maleate and diethyl dianilino fumarate from the retention time of the standard substance by high performance liquid chromatography (HPLC). The yield and purity as diethyl 1,2-dianilino-1,2-ethylenedicarboxylate based on the HPLC area ratio were 58.3% and 94.8%, respectively.

Comparative Example Step 1 ′:
A reactor was charged with 21.5 parts of p-toluidine, 24.5 parts of ethyl chloroacetate, 11.6 parts of sodium carbonate and 80 parts of dehydrated ethanol, and reacted at 78 ° C. for 24 hours with stirring in a nitrogen atmosphere. To yield ester (C3).
300 parts of water was added and stirred for 30 minutes, cooled to 0 ° C., filtered, washed with 100 parts of water / ethanol = 8/1 aqueous solution and 30 parts of cooled ethanol in this order, and vacuumed at 40 ° C. When dried, 27.0 parts of a powder believed to be ester (C3) was obtained.
The powder was found to be ethyl p-toluidinoacetate from the retention time of the standard substance by high performance liquid chromatography (HPLC). The yield and purity of ethyl p-toluidinoacetate based on the HPLC area ratio were 70% and 97.8%, respectively.

Step 2'-4 ':
In a reactor, 400 parts of dehydrated ethanol and 71.4 parts of sodium ethoxide were charged with stirring in a nitrogen atmosphere at 55 ° C., 146.1 parts of diethyl oxalate and ethyl p-toluidinoacetate 193 obtained above. 2 parts were added and reacted at 25 ° C. for 20 hours. Subsequently, the solvent was distilled off under reduced pressure.
After adding 750 parts of water and 72 parts of acetic acid and stirring vigorously, stirring was stopped, 500 parts of toluene was added and stirring was performed again, followed by standing for 2 hours, separating the toluene layer The water layer was extracted with 2 × 200 parts of toluene, and the toluene layers were combined and washed with 600 parts of water.
Toluene was distilled off under reduced pressure, 96.5 parts of p-toluidine, 600 parts of ethanol and 9 parts of 35% aqueous hydrogen chloride were added, and the reaction was carried out at 78 ° C. for 6 hours.

  Next, the mixture was cooled to 0 ° C., filtered, washed and dried to obtain 221.6 parts of a powder which seems to be ester (G3). This was found to be diethyl 1,2-di-p-toluidino-1,2-ethylenedicarboxylate from a molecular ion peak by mass spectrometry. The yield and purity as diethyl 1,2-di-p-toluidino-1,2-ethylenedicarboxylate based on the HPLC area ratio were 41% and 96.8%, respectively.

Since the production method of the comparative example, which is a conventional method, uses only a small amount of alkali metal carbonate, which is a basic catalyst, the yield in step 1 (corresponding) is remarkably low, and purification by separation or the like in the middle, etc. Or taking out from the reaction apparatus and recharging, the yield of 1,2-diarylamino-1,2-ethylenedicarboxylic acid alkyl ester finally obtained is remarkably lowered.
On the other hand, in the production method of Example 1 of the present invention, a relatively large amount of alkali metal carbonate as a basic catalyst is used, and an anhydrous organic solvent is used as a solvent. It is clear that 1,2-diarylamino-1,2-ethylenedicarboxylic acid alkyl ester can be obtained in a higher yield.

Claims (2)

In the process for producing 1,2-diarylamino-1,2-ethylenedicarboxylic acid alkyl ester comprising the following steps:
Performing step 1 in an anhydrous alcohol as an organic solvent, using an alkali metal carbonate as a basic catalyst in the following step 1 in an amount larger than the hydrogen halide to be produced,
The following steps 1 to 4 are performed in the same reactor without purifying the reaction mixture in each step.
A process for producing a 1,2-diarylamino-1,2-ethylenedicarboxylic acid alkyl ester, characterized in that
Step 1: An anilinoacetic acid alkyl ester compound is obtained by dehydrohalogenating an aniline compound and a halogenoacetic acid alkyl ester compound in an organic solvent in the presence of a basic catalyst.
Step 2: The reaction product is obtained by subjecting the anilinoacetic acid alkyl ester compound and oxalic acid di-lower alkyl ester compound to a nucleophilic substitution reaction.
Step 3: The reaction product is hydrolyzed with an acid to obtain an intermediate.
Step 4: The intermediate is reacted with an aniline compound to obtain 1,2-diarylamino-1,2-ethylenedicarboxylic acid alkyl ester. The process according to claim 1, wherein the 1,2-diarylamino-1,2-ethylenedicarboxylic acid alkyl ester is a mixture of a diarylaminomaleic acid dialkyl ester and a diarylaminofumaric acid dialkyl ester.