Novel catalytic process method for 2, 5-dimethoxy-4-chloracetylacetanilide

Abstract

The invention discloses a novel catalytic process method for 2, 5-dimethoxy-4-chloracetylacetanilide, and belongs to the field of chemical synthesis. The preparation method comprises the following steps: mixing 2, 5-dimethoxy-4-chloroaniline, an ionic liquid catalyst, a reaction mother solution and diketene, reacting for 1-1.5 hours at the reaction temperature of 10-20 DEG C, and cooling, filtering and drying after the reaction is completed to obtain a finished product. According to the invention, 2, 5-dimethoxy-4-chloroaniline and diketene are taken as raw materials, one-step synthesis is carried out by adopting acylation reaction catalyzed by the ionic liquid, the target product selectivity is high, and pollution is less during post-treatment; due to the introduction of the ionic liquid catalyst, the electrophilicity of the aromatic ring compound is improved, the reaction is easier to carry out, and the ionic liquid catalyst is green, non-toxic, recyclable and easy for industrial production; and the mother liquor can be continuously used as an indiscriminate mother liquor for next reaction.

Description

Technical Field

[0001] The invention relates to a novel catalytic process method for 2,5-dimethoxy-4-chloroacetoacetanilide, and belongs to the field of chemical synthesis. Background Art

[0002] 2,5-Dimethoxy-4-chloroacetoacetanilide is suitable for dyeing cotton, viscose fiber and cotton cloth printing. It is a primer for yellow dyeing. It can be coupled with yellow base to obtain green light yellow and with orange salt GGD to obtain bright orange. It has bright color and excellent light fastness. It is suitable for producing cotton products with high fastness requirements. It is also an intermediate for preparing organic pigments and is used to synthesize pigment yellow 83 and ice dye.

[0003] At present, the mainstream process for synthesizing 2,5-dimethoxy-4-chloroacetoacetanilide is to synthesize 2,5-dimethoxy-4-chloroacetoacetanilide from diketene and 2,5-dimethoxy-4-chloroacetoacetanilide in an alcohol solvent. Since diketene undergoes self-polymerization in the above reaction system and 2,5-dimethoxy-4-chloroacetoacetanilide is easily decomposed into 2,5-dimethoxy-4-chloroacetoacetanilide at high temperatures, it is necessary to increase the proportion of diketene to promote the forward reaction, resulting in a large consumption of raw materials. At the same time, in the acylation process, the chlorine atom, as a strong electron-withdrawing group, uses the inductive effect to passivate the benzene ring, resulting in a slow reaction rate, a long reaction time, incomplete raw material conversion, and poor product quality.

[0004] Patent CN 104119247A reports a method for preparing 4-chloro-2,5-dimethoxyacetoacetanilide, which comprises adding an organic solvent and 4-chloro-2,5-dimethoxyaniline to a reaction vessel as a base, dropping diketene at 20 to 60°C, and finishing the dropping for 0.5 to 5 hours. The mixture is kept warm for 0.5 to 4 hours, cooled, discharged, and filtered. The crystals are 4-chloro-2,5-dimethoxyacetoacetanilide, and the filtrate is recycled. The yield of the prepared product is 97% and the output content is 99.5%. The dropping and keeping warm time of this method is long, and the production efficiency is not high.

[0005] Patent CN 116003278A reports a method for preparing 4-chloro-2,5-dimethoxyacetoacetanilide, wherein diketene and 2,5-dimethoxy-4-chloroaniline are added to a mother liquor in equal molar ratios for acylation reaction, the reaction temperature is raised to 60°C, and then the reaction solution is gradually heated to dissolve completely, activated carbon is added, filtered while hot, and then seed crystals are added in batches for crystallization, and the product is obtained after cooling. The method requires a high reaction temperature, generates more by-products and impurities, and reduces the product quality.

[0006] The disadvantages of the original process are:

[0007] (1) Diketene undergoes a self-polymerization reaction in the above reaction system, and 2,5-dimethoxy-4-chloroacetoacetanilide is easily decomposed into 2,5-dimethoxy-4-chloroacetoacetanilide at a high temperature;

[0008] (2) Chlorine atoms are strong electron-withdrawing groups, which make the benzene ring passivated and the acylation reaction is not easy to occur;

[0009] (3) It takes a long time and the production efficiency is low;

[0010] (4) The required reaction temperature is high, and more by-products and impurities are generated, which reduces the product quality.

[0011] In view of the problems existing in the existing process routes and the technical challenges of one-step acylation, the present invention uses 2,5-dimethoxy-4-chloroaniline and diketene as raw materials and adopts an acylation reaction catalyzed by ionic liquid for one-step synthesis. Compared with the previous synthesis routes, this method has high selectivity for the target product and less pollution during post-treatment. Summary of the invention

[0012] The invention provides a novel catalytic process for 2,5-dimethoxy-4-chloroacetoacetanilide. The method comprises the following steps: mixing 2,5-dimethoxy-4-chloroaniline, an ionic liquid catalyst, a reaction mother liquor and diketene to carry out an acylation reaction. After the reaction is completed, the mixture is cooled, filtered and dried to obtain a finished product. The ionic liquid catalyst is [Bmim]Br and AlCl3. The reaction mother liquor is prepared by adding diketene and 2,5-dimethoxy-4-chloroaniline in equal molar ratios to ethanol having a mass concentration of 95%. The method comprises the steps of: reacting in a solution at 45°C to obtain a reaction solution; heating the reaction solution to 60°C to fully dissolve the reaction solution, adding activated carbon, filtering the reaction solution while hot, cooling the reaction solution at a rate of 6-8°C / h after filtration, and adding rod-shaped or cubic crystal seeds with a particle size of 40-80 meshes in batches according to the temperature reduction gradient; when crystals begin to precipitate, maintaining the temperature for 0.5-1h to grow the crystals, cooling the reaction solution at a rate of 12-15°C / h after the temperature is maintained, and crystallization is completed when the temperature drops to 10°C. After centrifugation, the crystals are separated to obtain a reaction mother solution with a mass concentration of 80%-90%.

[0013] In one embodiment of the present invention, the method is as follows:

[0014] (1) [Bmim]Br and anhydrous AlCl3 were mixed in a molar ratio of 1:0.5-1.5, heated to 70°C in a magnetic heating stirrer, and kept warm for 2 hours to obtain a uniform transparent ionic liquid;

[0015] (2) adding 2,5-dimethoxy-4-chloroaniline and reaction mother liquor into a reaction kettle at a mass ratio of 1:2.5-3.5, controlling the initial reaction temperature at 10-15° C., and adding an ionic liquid catalyst having a mass fraction of 0.01-0.05% of 2,5-dimethoxy-4-chloroaniline;

[0016] (3) adding diketone in a molar ratio of 2,5-dimethoxy-4-chloroaniline to diketone of 1:1.01-1.05, with a dropwise addition time of 1-2 hours and a reaction temperature of 15-20° C. during the dropwise addition process;

[0017] (4) After the reaction is completed, the temperature is raised to 65°C to completely dissolve the reactants, and then the reactants are decolorized by passing through an activated carbon fiber adsorption column while hot. After the decolorization is completed, the temperature is lowered and crystallized to obtain the finished product, and the mother liquor is used as the mother liquor for the next reaction.

[0018] In one embodiment, the ionic liquid catalyst in step (1) is obtained by mixing [Bmim]Br and anhydrous AlCl3 in a molar ratio of 1:1, heating to 70°C in a magnetic heating stirrer, and keeping warm for 2 hours.

[0019] In one embodiment, the amount of the ionic liquid catalyst added in step (2) is 0.01 to 0.05% by mass fraction of 2,5-dimethoxy-4-chloroaniline, preferably 0.03%.

[0020] In one embodiment, the 2,5-dimethoxy-4-chloroaniline and the reaction mother liquor in step (2) are added to the reaction kettle in a mass ratio of 1:3.

[0021] In one embodiment, the initial reaction temperature in step (2) is 10-15°C, preferably 13°C.

[0022] In one embodiment, the diketene in step (3) is added dropwise in a molar ratio of 2,5-dimethoxy-4-chloroaniline to diketene of 1:1.01-1.05, the addition time is 1-2 hours, and the reaction temperature during the addition process is 10-20°C; preferably, the addition time is 1 hour, and the reaction temperature during the addition process is 15°C.

[0023] In one embodiment, after the reaction in step (4) is completed, the temperature is raised to 65°C for complete dissolution, and then the mixture is passed through an activated carbon fiber adsorption column (flow rate of 4 BV / h, pore size of 10-30 nm) for decolorization while hot. After decolorization for 0.5 h, the temperature is lowered to 47°C to precipitate crystals, and then the crystals are grown at 47°C for 1 h. The temperature is further lowered to below 10°C and centrifuged to obtain a damp product and a centrifuged mother liquor. The damp product is washed and dried to obtain a finished product.

[0024] In one embodiment, the mother liquor in step (4) is a centrifugal mother liquor, which contains an ionic liquid and can be used as a mother liquor for the next batch of reactions.

[0025] In one embodiment, the synthetic route of the present invention is:

[0026]

[0027] The ionic liquid [Bmim]Br-AlCl3 complexes with diketene to form an acyl cation, which then undergoes an electrophilic substitution reaction with 2,5-dimethoxy-4-chloroaniline to form a complex of 2,5-dimethoxy-4-chloroacetoacetanilide and [Bmim]Br-AlCl3, and finally [Bmim]Br-AlCl3 dissociates to generate the target product.

[0028] The present invention also provides an application of the preparation method in preparing 2,5-dimethoxy-4-chloroacetoacetanilide or a product containing 2,5-dimethoxy-4-chloroacetoacetanilide, wherein the yield of 2,5-dimethoxy-4-chloroacetoacetanilide is 95.40-96.68%, the purity is 99.80-99.99%, and the by-product acetylated impurities and enol isomers are 10-50 ppm.

[0029] Beneficial Effects

[0030] (1) The ionic liquid and diketene complex to form acyl cations, which promote the electrophilic substitution reaction of aromatic compounds, greatly shorten the reaction time, and also reduce the self-polymerization of diketene;

[0031] (2) Low temperature reaction reduces the generation of impurities, improves product quality, and reduces production energy consumption;

[0032] (3) Ionic liquid catalysts are green and non-toxic, can be recycled, and are easy to industrialize;

[0033] (4) The particle size distribution of the prepared product is 30-60 mesh, and no agglomeration occurs after being placed for 100 days;

[0034] (5) The mother liquor can be used as the mother liquor for the next reaction, and the number of cycles is 20 to 30;

[0035] (6) The product purity is greater than 99.80%, and the by-product acetylated impurities and enol isomers are less than 50 ppm. DETAILED DESCRIPTION

[0036] 1. The chemical structure analysis of 2,5-dimethoxy-4-chloroacetoacetanilide involved in the following examples is as follows:

[0037] Appearance: White to off-white flaky crystalline powder

[0038] Structural formula:

[0039] Molecular formula: C 12 H 14 ClNO4;

[0040] CAS No.: 4433-79-8;

[0041] Molecular weight: 271.7;

[0042] Melting point (℃): 102;

[0043] Density (g / cm 3 ):1.277;

[0044] Boiling point (℃): 432.7;

[0045] Flash point(℃):215.5.

[0046] 2. The detection method / calculation formula involved in the following embodiments:

[0047] Purity test of 2,5-dimethoxy-4-chloroacetoacetanilide:

[0048] Purity (%) = ((sample peak area / external standard peak area)) × content of compound in sample (%)) / sample mass

[0049] Among them, the sample peak area is the compound peak area on the HPLC chromatogram, the external standard peak area is the external standard peak area on the HPLC chromatogram, the content of the compound in the external standard sample is the known content of the compound in the external standard sample, and the sample mass is the mass of the sample to be tested.

[0050] Calculation formula for the yield of 2,5-dimethoxy-4-chloroacetoacetanilide:

[0051] Yield = n1 / n2, n1 is the amount of 2,5-dimethoxy-4-chloroacetoacetanilide, n2 is the amount of 2,5-dimethoxy-4-chloroaniline

[0052] 3. [Bmim]Br (CAS No.: 85100-77-2) and anhydrous AlCl3 involved in the following examples were purchased from Macklin reagent; 2,5-dimethoxy-4-chloroaniline (CAS No.: 6358-64-1) was purchased from Jiangsu Pules Biotechnology Co., Ltd.; diketene (CAS No.: 674-82-8) was purchased from Zhangjiagang Haobo Chemical Co., Ltd.; the preparation method of the reaction mother solution can refer to the Chinese invention patent application document with publication number CN 116003278 A, and the specific preparation method is as follows:

[0053] (1) adding diketene and 2,5-dimethoxy-4-chloroaniline in equal molar ratios to a 95% ethanol solution at 45° C. to carry out an acylation reaction to obtain a reaction solution;

[0054] (2) The reaction solution is gradually heated to 60°C and completely dissolved, and then activated carbon is added and filtered while hot. After the activated carbon is filtered, the temperature is lowered, and the cooling rate is controlled to be 6-8°C / h. Rod-shaped or cubic seed crystals with a particle size of 40-80 mesh are added in batches according to the cooling gradient;

[0055] (3) When crystals begin to precipitate, the temperature is kept at 0.5 to 1 h for crystal growth. After the temperature is kept at 10 ° C, the crystallization is completed. After the crystals are separated by centrifugation, a reaction mother liquor with a mass concentration of 80% to 90% is obtained.

[0056] In addition, the above reaction mother liquor can also be directly taken from the production workshop of Nantong Acetic Acid Chemical Co., Ltd.

[0057] Example 1: A novel catalytic process for 2,5-dimethoxy-4-chloroacetoacetanilide

[0058] The specific implementation is as follows:

[0059] 1. Preparation of 2,5-dimethoxy-4-chloroacetoacetanilide

[0060] (1) Preparation of ionic liquid catalysts:

[0061] [Bmim]Br was used as a solvent and mixed with anhydrous AlCl3 in a molar ratio of 1:1, and heated to 70°C in a magnetic heating stirrer at a speed of 100 r / min for 2 h to obtain a uniform and transparent ionic liquid.

[0062] (2) 75 g of 2,5-dimethoxy-4-chloroaniline and 225 g of the reaction mother liquor were added to a reaction kettle, cooled with a brine water bath and the initial reaction temperature was controlled at 10°C, and the ionic liquid catalyst obtained in step (1) was added in an amount of 0.01% of the mass fraction of 2,5-dimethoxy-4-chloroaniline. Then, 36.4 g of diketene with a content of 99.0% was added dropwise to the above mixture to continue the reaction, the addition time was 1 hour, and the reaction temperature was controlled at 15°C during the addition process in a water bath.

[0063] (3) After the reaction is completed, the reactants are completely dissolved by steam heating to 65°C, and then decolorized by an activated carbon fiber adsorption column (flow rate of 4BV / h, pore size of 10-30nm) while hot. After decolorization for 0.5h, the temperature is lowered to 47°C to precipitate crystals, and then the crystals are grown at 47°C for 1h. The temperature is further lowered to below 10°C, and a damp product and a centrifugal mother liquor are obtained by centrifugation (the centrifugal mother liquor is used as the solvent for the next batch). The damp product is washed and dried to obtain a finished product. The product yield is 95.55%, the product purity is 99.88%, the content of by-product acetylated impurities and enol isomers is 10ppm, the product particle size is 30-60 mesh, and no agglomeration occurs after being placed for 100d.

[0064] 2. Mother liquor circulation experiment

[0065] The centrifuged mother liquor in step (3) was used 10 times, and the other conditions remained unchanged. When the centrifuged mother liquor was used for the 10th time, the product yield was 95.68%, the product purity was 99.87%, the content of by-product acetylated impurities and enol isomers was 43 ppm, the product particle size was 30-60 mesh, and no agglomeration occurred after being placed for 100 days.

[0066] Example 2: A novel catalytic process for 2,5-dimethoxy-4-chloroacetoacetanilide

[0067] The specific implementation is as follows:

[0068] 1. Preparation of 2,5-dimethoxy-4-chloroacetoacetanilide

[0069] (1) Preparation of ionic liquid catalysts:

[0070] [Bmim]Br was used as a solvent and mixed with anhydrous AlCl3 in a molar ratio of 1:1, and heated to 70°C in a magnetic heating stirrer at a speed of 100 r / min for 2 h to obtain a uniform and transparent ionic liquid.

[0071] (2) 75g of 2,5-dimethoxy-4-chloroaniline and 225g of reaction mother liquor were added to a reaction kettle, cooled with a brine water bath and the initial reaction temperature was controlled at 10°C, and the ionic liquid catalyst obtained in step (1) was added in an amount of 0.05% of the mass fraction of 2,5-dimethoxy-4-chloroaniline. Then, 36.4g of diketene with a content of 99.0% was added dropwise to the above mixture to continue the reaction, the addition time was 1h, and the reaction temperature was controlled at 15°C during the addition process in a water bath.

[0072] (3) After the reaction is completed, the temperature is raised to 65°C by steam heating to completely dissolve the reactants, and then the reactants are decolorized by passing through an activated carbon fiber adsorption column (flow rate of 4 BV / h, pore size of 10-30 nm) while hot. After decolorization for 0.5 h, the temperature is lowered to 47°C to precipitate crystals, and then the crystals are grown at 47°C for 1 h. The temperature is further lowered to below 10°C, and a damp product and a centrifugal mother liquor are obtained by centrifugation (the centrifugal mother liquor is used as the solvent for the next batch). The damp product is washed and dried to obtain a finished product. The product yield is 96.12%, the product purity is 99.91%, the content of by-product acetylated impurities and enol isomers is 12 ppm, the product particle size is 30-60 mesh, and no agglomeration occurs after being placed for 100 days.

[0073] 2. Mother liquor circulation experiment

[0074] The centrifuged mother liquor in step (3) was used 10 times, and the other conditions remained unchanged. When the centrifuged mother liquor was used for the 10th time, the product yield was 96.08%, the product purity was 99.89%, the content of by-product acetylated impurities and enol isomers was 36 ppm, the product particle size was 30-60 mesh, and no agglomeration occurred after being placed for 100 days.

[0075] Example 3: A novel catalytic process for 2,5-dimethoxy-4-chloroacetoacetanilide

[0076] The specific implementation is as follows:

[0077] 1. Preparation of 2,5-dimethoxy-4-chloroacetoacetanilide

[0078] (1) Preparation of ionic liquid catalysts:

[0079] [Bmim]Br was used as a solvent and mixed with anhydrous AlCl3 in a molar ratio of 1:1, and heated to 70°C in a magnetic heating stirrer at a speed of 100 r / min for 2 h to obtain a uniform and transparent ionic liquid.

[0080] (2) 75 g of 2,5-dimethoxy-4-chloroaniline and 225 g of the reaction mother liquor were added to a reaction kettle, cooled with a brine water bath and the initial reaction temperature was controlled at 10°C, and the ionic liquid catalyst obtained in step (1) was added in an amount of 0.03% of the mass fraction of 2,5-dimethoxy-4-chloroaniline. Then, 36.4 g of diketene with a content of 99.0% was added dropwise to the above mixture to continue the reaction, the addition time was 1 hour, and the reaction temperature was controlled at 15°C during the addition process in a water bath.

[0081] (3) After the reaction is completed, the temperature is raised to 65°C by steam heating to completely dissolve the reactants, and then the reactants are decolorized by passing through an activated carbon fiber adsorption column (flow rate of 4 BV / h, pore size of 10-30 nm) while hot. After decolorization for 0.5 h, the temperature is lowered to 47°C to precipitate crystals, and then the crystals are grown at 47°C for 1 h. The temperature is further lowered to below 10°C, and a damp product and a centrifugal mother liquor are obtained by centrifugation (the centrifugal mother liquor is used as the solvent for the next batch). The damp product is washed and dried to obtain a finished product. The product yield is 96.65%, the product purity is 99.93%, the content of by-product acetylated impurities and enol isomers is 16 ppm, the product particle size is 30-60 mesh, and no agglomeration occurs after being placed for 100 days.

[0082] 2. Mother liquor circulation experiment

[0083] The centrifuged mother liquor in step (3) was used 10 times, and the other conditions remained unchanged. When the centrifuged mother liquor was used for the 10th time, the product yield was 96.58%, the product purity was 99.93%, the content of by-product acetylated impurities and enol isomers was 40 ppm, the product particle size was 30-60 mesh, and no agglomeration occurred after being placed for 100 days.

[0084] Example 4: A novel catalytic process for 2,5-dimethoxy-4-chloroacetoacetanilide

[0085] The specific implementation is as follows:

[0086] 1. Preparation of 2,5-dimethoxy-4-chloroacetoacetanilide

[0087] (1) Preparation of ionic liquid catalysts:

[0088] [Bmim]Br was used as a solvent and mixed with anhydrous AlCl3 in a molar ratio of 1:1, and heated to 70°C in a magnetic heating stirrer at a speed of 100 r / min for 2 h to obtain a uniform and transparent ionic liquid.

[0089] (2) 75 g of 2,5-dimethoxy-4-chloroaniline and 225 g of the reaction mother liquor were added to a reaction kettle, cooled with a brine water bath and the initial reaction temperature was controlled at 13° C. The ionic liquid catalyst obtained in step (1) was added in an amount of 0.03% of the mass fraction of 2,5-dimethoxy-4-chloroaniline. Then, 36.4 g of diketene with a content of 99.0% was added dropwise to the above mixture to continue the reaction. The addition time was 1 hour, and the reaction temperature was controlled at 15° C. during the addition process in a water bath.

[0090] (3) After the reaction is completed, the temperature is raised to 65°C by steam heating to completely dissolve the reactants, and then the reactants are decolorized by passing through an activated carbon fiber adsorption column (flow rate of 4 BV / h, pore size of 10-30 nm) while hot. After decolorization for 0.5 h, the temperature is lowered to 47°C to precipitate crystals, and then the crystals are grown at 47°C for 1 h. The temperature is further lowered to below 10°C, and a damp product and a centrifugal mother liquor are obtained by centrifugation (the centrifugal mother liquor is used as the solvent for the next batch). The damp product is washed and dried to obtain a finished product. The product yield is 96.23%, the product purity is 99.93%, the content of by-product acetylated impurities and enol isomers is 20 ppm, the product particle size is 30-60 mesh, and no agglomeration occurs after being placed for 100 days.

[0091] 2. Mother liquor circulation experiment

[0092] The centrifuged mother liquor in step (3) was used 20 times, and the other conditions remained unchanged. When the centrifuged mother liquor was used for the 20th time, the product yield was 96.16%, the product purity was 99.92%, the content of by-product acetylated impurities and enol isomers was 48 ppm, the product particle size was 30-60 mesh, and no agglomeration occurred after being placed for 100 days.

[0093] Example 5: A novel catalytic process for 2,5-dimethoxy-4-chloroacetoacetanilide

[0094] The specific implementation is as follows:

[0095] 1. Preparation of 2,5-dimethoxy-4-chloroacetoacetanilide

[0096] (1) Preparation of ionic liquid catalysts:

[0097] [Bmim]Br was used as a solvent and mixed with anhydrous AlCl3 in a molar ratio of 1:1, and heated to 70°C in a magnetic heating stirrer at a speed of 100 r / min for 2 h to obtain a uniform and transparent ionic liquid.

[0098] (2) 75 g of 2,5-dimethoxy-4-chloroaniline and 225 g of the reaction mother liquor were added to a reaction kettle, cooled with a brine water bath and the initial reaction temperature was controlled at 15°C, and the ionic liquid catalyst obtained in step (1) was added in an amount of 0.01% of the mass fraction of 2,5-dimethoxy-4-chloroaniline. Then, 36.4 g of diketene with a content of 99.0% was added dropwise to the above mixture to continue the reaction, and the addition time was 1 hour. The reaction temperature was controlled at 15°C in a water bath during the entire addition process.

[0099] (3) After the reaction is completed, the temperature is raised to 65°C by steam heating to completely dissolve the reactants, and then the reactants are decolorized while hot by passing through an activated carbon fiber adsorption column (flow rate of 4 BV / h, pore size of 10-30 nm). After decolorization for 0.5 h, the temperature is lowered to 47°C to precipitate crystals, and then the crystals are grown at 47°C for 1 h. The temperature is further lowered to below 10°C, and a damp product and a centrifugal mother liquor are obtained by centrifugation (the centrifugal mother liquor is used as the solvent for the next batch). The damp product is washed and dried to obtain a finished product. The product yield is 96.01%, the product purity is 99.91%, the content of by-product acetylated impurities and enol isomers is 37 ppm, the product particle size is 30-60 mesh, and no agglomeration occurs after being placed for 100 days.

[0100] 2. Mother liquor circulation experiment

[0101] The centrifuged mother liquor in step (3) was used 20 times, and the other conditions remained unchanged. When the centrifuged mother liquor was used for the 20th time, the product yield was 95.32%, the product purity was 99.91%, the content of by-product acetylated impurities and enol isomers was 45 ppm, the product particle size was 30-60 mesh, and no agglomeration occurred after being placed for 100 days.

[0102] Example 6: A novel catalytic process for 2,5-dimethoxy-4-chloroacetoacetanilide

[0103] Referring to Example 1, the difference is that the dropping time is adjusted to 1.5 h, and other conditions remain unchanged to prepare 2,5-dimethoxy-4-chloroacetoacetanilide.

[0104] Results: The product yield was 95.59%, the product purity was 99.88%, the content of by-product acetylated impurities and enol isomers was 200 ppm, the product particle size was 50-80 mesh, and agglomeration occurred after being left for 100 days.

[0105] When the centrifugal mother liquor was used for the 10th time, the product yield was 96.01%, the product purity was 99.73%, the content of by-product acetylated impurities and enol isomers was 600 ppm, the product particle size was 50-80 mesh, and agglomeration occurred after being left for 100 days.

[0106] Example 7: A novel catalytic process for 2,5-dimethoxy-4-chloroacetoacetanilide

[0107] Referring to Example 1, the difference is that the reaction temperature during the dropping process is adjusted to 13° C., and other conditions remain unchanged to prepare 2,5-dimethoxy-4-chloroacetoacetanilide.

[0108] Results: The product yield was 95.43%, the product purity was 99.35%, the content of by-product acetylated impurities and enol isomers was 650 ppm, the product particle size was 50-80 mesh, and agglomeration occurred after being left for 100 days.

[0109] When the centrifugal mother liquor was used for the 10th time, the product yield was 95.51%, the product purity was 99.23%, the content of by-product acetylated impurities and enol isomers was 900 ppm, the product particle size was 50-80 mesh, and agglomeration occurred after being left for 100 days.

[0110] Comparative Example 1: A novel catalytic process for 2,5-dimethoxy-4-chloroacetoacetanilide

[0111] Referring to Example 4, except that no ionic liquid catalyst was added and other conditions remained unchanged, 2,5-dimethoxy-4-chloroacetoacetanilide was prepared.

[0112] The specific implementation is as follows:

[0113] 1. Preparation of 2,5-dimethoxy-4-chloroacetoacetanilide

[0114] (1) 75 g of 2,5-dimethoxy-4-chloroaniline and 225 g of the reaction mother liquor were added to a reaction kettle, cooled with a brine water bath and the initial reaction temperature was controlled at 13° C. Then, 36.4 g of diketene with a content of 99.0% was added dropwise to the above mixture to continue the reaction. The addition time was 1 hour, and the reaction temperature was controlled at 15° C. in a water bath during the addition process.

[0115] (2) After the reaction is completed, the temperature is raised to 65°C by steam heating to completely dissolve the reactants, and then the reactants are decolorized by passing through an activated carbon fiber adsorption column (flow rate of 4 BV / h, pore size of 10-30 nm) while hot. After decolorization for 0.5 h, the temperature is lowered to 47°C to precipitate crystals, and then the crystals are grown at 47°C for 1 h. The temperature is further lowered to below 10°C, and a damp product and a centrifugal mother liquor are obtained by centrifugation (the centrifugal mother liquor is used as the solvent for the next batch). The damp product is washed and dried to obtain a finished product. The product yield is 53.25%, the product purity is 89.28%, the content of by-product acetylated impurities and enol isomers is 0.14%, the product particle size is 30-60 mesh, and no agglomeration occurs after being placed for 100 days.

[0116] 2. Mother liquor circulation experiment

[0117] The centrifuged mother liquor in step (2) was used for 5 times, and the other conditions remained unchanged. When the centrifuged mother liquor was used for the 5th time, the product yield was 52.11%, the product purity was 88.59%, the content of by-product acetylated impurities and enol isomers was 0.23%, the product particle size was 30-80 mesh, and agglomeration occurred after being left for 100 days.

[0118] Comparative Example 2: A novel catalytic process for 2,5-dimethoxy-4-chloroacetoacetanilide

[0119] Refer to Example 4, except that the reaction temperature during the dropping process is adjusted to 50° C. and other conditions remain unchanged to prepare 2,5-dimethoxy-4-chloroacetoacetanilide.

[0120] Results: The product yield was 86.32%, the product purity was 90.36%, the content of by-product acetylated impurities and enol isomers was 0.11%, the product particle size was 30-60 mesh, and no agglomeration occurred after being placed for 100 days.

[0121] The centrifugal mother liquor was used 5 times, and the other conditions remained unchanged. When the centrifugal mother liquor was used for the fifth time, the product yield was 86.55%, the product purity was 89.03%, the content of by-product acetylated impurities and enol isomers was 0.26%, the product particle size was 60-80 mesh, and agglomeration occurred after being left for 100 days.

[0122] Comparative Example 3: A novel catalytic process for 2,5-dimethoxy-4-chloroacetoacetanilide

[0123] Referring to Example 4, the only difference is that the decolorization is carried out by activated carbon, and other conditions remain unchanged to prepare 2,5-dimethoxy-4-chloroacetoacetanilide.

[0124] Results: The product yield was 94.21%, the product purity was 99.53%, the content of by-product acetylated impurities and enol isomers was 46 ppm, the product particle size was 30-60 mesh, and no agglomeration occurred after being placed for 100 days.

[0125] The centrifugal mother liquor was used 5 times, and the other conditions remained unchanged. When the centrifugal mother liquor was used for the fifth time, the product yield was 94.02%, the product purity was 99.51%, the content of by-product acetylated impurities and enol isomers was 42ppm, the product particle size was 30-60 mesh, and no agglomeration occurred after being placed for 100 days.

[0126] Comparative Example 4: A novel catalytic process for 2,5-dimethoxy-4-chloroacetoacetanilide

[0127] Referring to Example 4, the only difference is that the ionic liquid is adjusted to [Bmim]Br-FeCl3, and other conditions remain unchanged to prepare 2,5-dimethoxy-4-chloroacetoacetanilide.

[0128] Results: The product yield was 90.11%, the product purity was 99.53%, the content of by-product acetylated impurities and enol isomers was 200 ppm, the product particle size was 30-70 mesh, and no agglomeration occurred after being placed for 100 days.

[0129] The centrifugal mother liquor was used 5 times, and the other conditions remained unchanged. When the centrifugal mother liquor was used for the fifth time, the product yield was 90.02%, the product purity was 99.15%, the content of by-product acetylated impurities and enol isomers was 500ppm, the product particle size was 30-70 mesh, and no agglomeration occurred after being placed for 100 days.

[0130] Comparative Example 5: A novel catalytic process for 2,5-dimethoxy-4-chloroacetoacetanilide

[0131] Referring to Example 4, the only difference is that the ionic liquid is adjusted to [Bmim]Br-ethylene glycol, and other conditions remain unchanged to prepare 2,5-dimethoxy-4-chloroacetoacetanilide.

[0132] Results: The product yield was 92.48%, the product purity was 98.89%, the content of by-product acetylated impurities and enol isomers was 0.16%, the product particle size was 30-60 mesh, and no agglomeration occurred after being placed for 100 days.

[0133] The centrifugal mother liquor was used 5 times, and the other conditions remained unchanged. When the centrifugal mother liquor was used for the fifth time, the product yield was 91.55%, the product purity was 98.11%, the content of by-product acetylated impurities and enol isomers was 0.24%, the product particle size was 30-70 mesh, and no agglomeration occurred after being placed for 100 days.

[0134] Comparative Example 6: A novel catalytic process for 2,5-dimethoxy-4-chloroacetoacetanilide

[0135] Referring to Example 4, the only difference is that the ionic liquid is adjusted to NMP-AlCl3, and other conditions remain unchanged to prepare 2,5-dimethoxy-4-chloroacetoacetanilide.

[0136] Results: The product yield was 94.65%, the product purity was 99.42%, the content of by-product acetylated impurities and enol isomers was 200 ppm, the product particle size was 30-60 mesh, and no agglomeration occurred after being placed for 100 days.

[0137] The centrifugal mother liquor was used 5 times, and the other conditions remained unchanged. When the centrifugal mother liquor was used for the fifth time, the product yield was 94.53%, the product purity was 99.12%, the content of by-product acetylated impurities and enol isomers was 500ppm, the product particle size was 30-60 mesh, and no agglomeration occurred after being placed for 100 days.

[0138] Comparative Example 7: A novel catalytic process for 2,5-dimethoxy-4-chloroacetoacetanilide

[0139] Referring to Example 4, the difference is that only [Bmim]Br is used as a catalyst, and other conditions remain unchanged to prepare 2,5-dimethoxy-4-chloroacetoacetanilide.

[0140] Results: The product yield was 86.22%, the product purity was 89.52%, the content of by-product acetylated impurities and enol isomers was 0.15%, the product particle size was 50-80 mesh, and agglomeration occurred after being placed for 100 days.

[0141] The centrifugal mother liquor was used 5 times, and the other conditions remained unchanged. When the centrifugal mother liquor was used for the fifth time, the product yield was 88.23%, the product purity was 87.23%, the content of by-product acetylated impurities and enol isomers was 0.53%, the product particle size was 50-80 mesh, and agglomeration occurred after being left for 100 days.

[0142] Comparative Example 8: A novel catalytic process for 2,5-dimethoxy-4-chloroacetoacetanilide

[0143] Refer to Example 4, except that the ionic liquid is adjusted to [Bmim]Br-ZnBr2, and other conditions remain unchanged to prepare 2,5-dimethoxy-4-chloroacetoacetanilide.

[0144] Results: The product yield was 93.22%, the product purity was 99.23%, the content of by-product acetylated impurities and enol isomers was 0.21%, the product particle size was 30-60 mesh, and no agglomeration occurred after being placed for 100 days.

[0145] The centrifugal mother liquor was used 5 times, and the other conditions remained unchanged. When the centrifugal mother liquor was used for the fifth time, the product yield was 93.01%, the product purity was 99.15%, the content of by-product acetylated impurities and enol isomers was 0.53%, the product particle size was 30-60 mesh, and no agglomeration occurred after being placed for 100 days.

[0146] Comparative Example 9: A novel catalytic process for 2,5-dimethoxy-4-chloroacetoacetanilide

[0147] Refer to Example 4, except that the ionic liquid is adjusted to Br2-AlCl3, and other conditions remain unchanged to prepare 2,5-dimethoxy-4-chloroacetoacetanilide.

[0148] Results: The product yield was 90.45%, the product purity was 98.23%, the content of by-product acetylated impurities and enol isomers was 100 ppm, the product particle size was 30-60 mesh, and no agglomeration occurred after being placed for 100 days.

[0149] The centrifugal mother liquor was used 5 times, and the other conditions remained unchanged. When the centrifugal mother liquor was used for the fifth time, the product yield was 92.41%, the product purity was 98.01%, the content of by-product acetylated impurities and enol isomers was 200ppm, the product particle size was 30-60 mesh, and no agglomeration occurred after being placed for 100 days.

[0150] Comparative Example 10: A novel catalytic process for 2,5-dimethoxy-4-chloroacetoacetanilide

[0151] Refer to Example 4, except that the ionic liquid is adjusted to Br2-ZnBr2, and other conditions remain unchanged to prepare 2,5-dimethoxy-4-chloroacetoacetanilide.

[0152] Results: The product yield was 89.56%, the product purity was 97.23%, the content of by-product acetylated impurities and enol isomers was 150ppm, the product particle size was 30-60 mesh, and no agglomeration occurred after being placed for 100 days.

[0153] The centrifugal mother liquor was used 5 times, and the other conditions remained unchanged. When the centrifugal mother liquor was used for the fifth time, the product yield was 90.23%, the product purity was 97.21%, the content of by-product acetylated impurities and enol isomers was 500ppm, the product particle size was 30-60 mesh, and no agglomeration occurred after being placed for 100 days.

[0154] Although the present invention has been disclosed as above in the form of a preferred embodiment, it is not intended to limit the present invention. Anyone familiar with this technology can make various changes and modifications without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention should be based on the definition of the claims.

Claims

1. A 2,5-dimethoxy-4-chloroacetoacetanilide catalytic method, characterized in that: The method comprises the following steps: mixing 2,5-dimethoxy-4-chloroaniline, an ionic liquid catalyst, a reaction mother solution and diketene, and reacting the mixture for 1 to 1.5 hours at a temperature of 10 to 20° C. After the reaction is completed, the mixture is cooled, filtered and dried to obtain a finished product. The ionic liquid catalyst is [Bmim]Br and AlCl3; The reaction mother liquor is prepared by adding diketene and 2,5-dimethoxy-4-chloroaniline in equal molar ratios to an ethanol solution with a mass concentration of 95% and reacting at 45°C to obtain a reaction liquid; heating the reaction liquid to 60°C to fully dissolve the reaction liquid, adding activated carbon and filtering it while hot; cooling it at a rate of 6-8°C / h after filtration, and adding rod-shaped or cubic crystal seeds with a particle size of 40-80 meshes in batches according to the temperature reduction gradient; when crystals begin to precipitate, keeping the temperature for 0.5-1h to grow the crystals, cooling it at a rate of 12-15°C / h after the heat preservation ends, and crystallization ends when the temperature drops to 10°C, and centrifuging to separate the crystals to obtain a reaction mother liquor with a mass concentration of 80%-90%.

2. The method according to claim 1, characterized in that The preparation method of the ionic liquid catalyst is as follows: [Bmim]Br and anhydrous AlCl3 are mixed in a substance ratio of 1:1 to 2, and after mixing, they are heated to 60 to 80°C and kept warm for 2 hours to obtain the catalyst.

3. The method according to claim 1, characterized in that The added amount of the ionic liquid catalyst is 0.01-0.05% of the mass fraction of 2,5-dimethoxy-4-chloroaniline.

4. The method according to claim 1, characterized in that: The diketene is added dropwise for reaction in a molar ratio of 2,5-dimethoxy-4-chloroaniline to diketene of 1:1.01-1.05, the reaction temperature of the dropwise addition process is 10-20° C., and the dropwise addition time is 1-2 hours.

5. The method according to claim 4, characterized in that The diketene is added dropwise at a molar ratio of 2,5-dimethoxy-4-chloroaniline to diketene of 1:1.03 for reaction, the reaction temperature during the dropwise addition process is 15° C., and the dropwise addition time is 1 hour.

6. The method according to claim 4, characterized in that Before diketene is added dropwise for reaction, the reaction temperature is 8 to 15°C.

7. The method according to claim 1, characterized in that The cooling is as follows: after the reaction is completed, the temperature is raised to 65° C. by steam heating, and the reactants are decolorized by passing through an activated carbon fiber adsorption column while hot, and then cooled after decolorization for 0.5 h.

8. The method according to claim 1, characterized in that The finished product is centrifugally dried after cooling to obtain a damp product and a centrifugal mother liquor, and the damp product is washed and dried to obtain a finished product.

9. The method according to claim 8, characterized in that The centrifugal mother liquor contains ionic liquid, and after the finished product is filtered, the ionic liquid and the centrifugal mother liquor are continuously used as the mother liquor for the next batch of reactions.

10. Use of the method according to any one of claims 1 to 9 in the preparation of 2,5-dimethoxy-4-chloroacetoacetanilide or a product containing 2,5-dimethoxy-4-chloroacetoacetanilide, wherein the yield of 2,5-dimethoxy-4-chloroacetoacetanilide is 95.40-96.68%, the purity is 99.80-99.99%, and the by-product acetylated impurities and enol isomers are 10-50 ppm.

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