A method for preparing isonicotinate with high conversion rate

Abstract

The present invention discloses a method for preparing isonicotinic acid ester with high conversion rate, which comprises the following steps: (1) Under nitrogen protection, isonicotinic acid, polyhydric alcohol and solid organic acid catalyst are added into a reactor; (2) The reactor is heated to 110-180 °C and reacted for 4-6 hours, and the generated water is separated by a water separator during the reaction process; (3) After the reaction is completed, the product is filtered, neutralized, and distilled under reduced pressure to obtain the isonicotinic acid ester. The water separator contains a water-carrying agent; the solid organic acid catalyst comprises a strongly acidic cation exchange resin and a metal chloride; the strongly acidic cation exchange resin has the structure shown in the following formula A. The method for preparing isonicotinic acid ester with high conversion rate provided by the present invention has high conversion rate and yield, less pollution and simple process flow.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and specifically relates to a method for preparing isonicotinic acid ester with high conversion rate. Background Art

[0002] Isonicotinic acid ester is a compound with a brownish-red or brown transparent solution and no pungent odor. It is not easily oxidized, does not change color, has good stability, has good skin moisturizing, spreading and permeability, and is a non-ionic surfactant that is non-toxic, non-irritating and does not cause allergic reactions.

[0003] The skin has good absorbability to isonicotinic acid ester, can closely contact with hair follicles in the cortex, penetrate deep into the cortex, and bring active components into it, giving full play to the role of active ingredients. When isonicotinic acid ester is added to cosmetics (the dosage is 2% - 5%), the product can be evenly applied on the skin, making the skin feel smooth but not greasy, and it is an excellent skin moisturizer; adding isonicotinic acid ester to lip balm can improve the structure and luster of the red paste. Therefore, isonicotinic acid ester is widely used in the formulations of creams, foundation creams, lipsticks, sunscreen oils, hair oils, mascaras, eyeshadow creams, inks, etc.

[0004] In addition, isonicotinic acid ester can be directly used as an additive for high-grade lubricating oils, a cutting oil, a coolant, a rolling oil, a drilling oil and other oil agents in high-grade instrument processing. Without affecting the efficiency, it can improve the oil quality, provide substitutes for petroleum products, and can also be used as a lubricant for textiles. Based on the above functions, isonicotinic acid ester is widely used in the synthetic lubricant industry, textile industry, petroleum industry, etc. At present, the annual consumption of isonicotinic acid ester in industries such as cosmetics and plastic processing has reached 1000 tons, and it is increasing at a rate of 8% - 10% per year.

[0005] Although isonicotinic acid ester has broad application prospects in the fields of lubricant industry, textile industry, petroleum industry, plastic processing industry, cosmetics, etc., there are very few domestic related manufacturers. In the preparation processes of isonicotinic acid ester by foreign manufacturers, concentrated sulfuric acid is mostly used as a catalyst. Although it has excellent catalytic activity, concentrated sulfuric acid has strong acidity, resulting in serious corrosion of equipment during the production process, frequent replacement of equipment, and increased production costs; concentrated sulfuric acid has strong oxidizing property, resulting in the reaction of alcohol and water to generate ether and produce coke, affecting product quality; a large amount of waste acid and waste water are generated during the production process, polluting the environment; concentrated sulfuric acid as a catalyst cannot be regenerated and reused, correspondingly increasing production costs; concentrated sulfuric acid is not easily separated from the product, and the post-treatment process is complex, increasing product costs. And the existing preparation methods of isonicotinic acid ester are relatively complex, with high costs and losses, and the conversion rate and yield of the reaction still need to be improved.

[0006] Therefore, there is an urgent need for a method for preparing isonicotinic acid ester with high conversion rate and yield, less pollution and simple process flow. Summary of the Invention

[0007] Objective of the Invention: Aiming at the defects of the prior art, the objective of the present invention is to provide a method for preparing isonicotinic acid ester with high conversion rate and high yield, less pollution and simple process flow.

[0008] Technical Solution:

[0009] A method for preparing isonicotinic acid ester with high conversion rate, comprising the following steps:

[0010] (1) Under the protection of nitrogen, add isonicotinic acid, polyhydric alcohol and solid organic acid catalyst into the reactor;

[0011] (2) Heat the reactor to 110 - 180 °C and react for 4 - 6 hours. During the reaction process, separate the generated water with a water separator;

[0012] (3) After the reaction is completed, filter, neutralize and distill the product under reduced pressure to obtain the isonicotinic acid ester;

[0013] The water separator contains a water-carrying agent;

[0014] The solid organic acid catalyst contains strongly acidic cation exchange resin and metal chloride;

[0015] The strongly acidic cation exchange resin has the structure shown in Formula A below:

[0016]

[0017] where n = 60 - 180.

[0018] For the method for preparing isonicotinic acid ester with high conversion rate provided by the present invention, the reaction components are simple, and a solid organic acid catalyst is used. On the one hand, it reduces the environmental pollution caused by liquid acid catalysts such as sulfuric acid, and on the other hand, it makes the product easy to separate, which can simplify the production process.

[0019] For the method for preparing isonicotinic acid ester with high conversion rate provided by the present invention, a solid organic acid catalyst is used as the reaction catalyst, which contains strongly acidic cation exchange resin and metal chloride, has strong catalytic ability and strong selectivity and specificity for the isonicotinic acid ester reaction, and can significantly improve the conversion rate and yield of the reaction.

[0020] Furthermore, in step (1), the molar ratio of isonicotinic acid to polyhydric alcohol is 1:1 - 1.5.

[0021] Furthermore, in step (1), the addition amount of the solid organic acid is 3 - 5% of the total mass of the reactants.

[0022] Furthermore, the water-carrying agent is selected from one of 4A molecular sieve or 5A molecular sieve.

[0023] The method for preparing isonicotinate with high conversion rate provided by the present invention adds molecular sieve as a water-carrying agent in a water separator, which has strong pertinence to water, only separates water, does not affect reactants and products, and the solid organic acid catalyst has a water-repellent effect, can quickly and cleanly remove the water generated by the reaction, and greatly improves the reaction conversion rate and yield.

[0024] Further, the metal chloride is selected from one of aluminum chloride, ferric chloride or chromium chloride; the mass ratio of the strongly acidic cation exchange resin to the metal chloride is 3 - 5:1.

[0025] Further, the strongly acidic cation exchange resin is prepared by the following steps:

[0026] (1) In a reactor, add N-(glycidyl)-N-phenyl-epoxyethanemethylamine and an organic solvent, stir and mix evenly, heat to 35 - 45 °C under nitrogen protection, then slowly dropwise add allyl bromide, the dropping time is 2 - 3 hours, after the dropping is completed, heat to 50 - 55 °C, keep the temperature for reaction for 18 - 24 hours, remove the solvent, and obtain the following compound B after recrystallization:

[0027]

[0028] (2) In a reactor, add divinylbenzene, compound B and an initiator, stir evenly and then heat to 80 - 95 °C for reaction for 4 - 6 hours, then cool to room temperature, filter, wash and dry to obtain the following compound C:

[0029] where n = 60 - 180;

[0030] (3) In a reactor, add compound C and tetrahydrofuran to swell for 8 - 12 hours, then add sodium sulfamate and an aqueous sodium hydroxide solution, heat to 80 - 100 °C, keep the temperature for reaction for 16 - 24 hours, then cool to room temperature, filter, wash and dry to obtain the strongly acidic cation exchange resin.

[0031] In the method for preparing isonicotinate with high conversion rate provided by the present invention, the strongly acidic cation exchange resin in the solid organic acid catalyst has multiple sulfonic acid functional groups, and they are dispersed in multiple branched chains, can quickly participate in the reaction of reactants, and have excellent catalytic ability; it contains multiple aromatic functional groups and multiple branched chain structures, and thus has relatively long arm chains, is easy to react with other substances and undergo ion exchange; due to its quaternary ammonium structure and aromatic structure, it has a large steric hindrance, increasing the contact volume with reactants, and thus has excellent catalytic ability; and the multiple aromatic functional groups in its structure endow it with excellent stability, and thus has a very long service life and can be recycled multiple times.

[0032] Further, in the step (1), the molar ratio of N-(glycidyl)-N-phenyl-oxiranemethanamine to allyl bromide is 1:1 - 1.2.

[0033] Further, in the step (2), the initiator is selected from one of benzoyl peroxide, tert-butyl peroxybenzoate or methyl ethyl ketone peroxide; the molar ratio of divinylbenzene to the compound of formula B is 1:2 - 2.2.

[0034] Further, in the step (3), the mass ratio of the compound of formula C to sodium sulfamate is 2 - 3:1.

[0035] Further, the preparation method of the solid organic acid catalyst is as follows: in a reactor, strong acidic cation exchange resin and metal chloride are added to an organic solvent, the temperature is raised to 80 - 90 °C, after heat preservation reaction for 16 - 24 hours, it is cooled to room temperature, filtered, washed and dried to obtain the solid organic acid catalyst.

[0036] Beneficial effects:

[0037] 1. The method for preparing isonicotinic acid ester with high conversion rate provided by the present invention uses a solid organic acid catalyst as the reaction catalyst, which contains strong acidic cation exchange resin and metal chloride, has strong catalytic ability and has strong selectivity and specificity for the reaction of isonicotinic acid ester, and can significantly improve the conversion rate and yield of the reaction.

[0038] 2. In the method for preparing isonicotinic acid ester with high conversion rate provided by the present invention, the strong acidic cation exchange resin in the solid organic acid catalyst has multiple sulfonic acid functional groups and is dispersed in multiple branched chains, can quickly participate in the reaction of reactants, and has excellent catalytic ability; contains multiple aromatic functional groups and multiple branched chain structures, and thus has a long arm chain, is easy to react with other substances and perform ion exchange; has a large steric hindrance through its quaternary ammonium structure and aromatic structure, increases the contact volume with the reactants, and thus has excellent catalytic ability; and the multiple aromatic functional groups in its structure endow it with excellent stability, and thus has a long service life and can be recycled multiple times.

[0039] 3. In the method for preparing isonicotinic acid ester with high conversion rate provided by the present invention, molecular sieve is added as a water-carrying agent in the water separator, which has strong pertinence to water, only separates water without affecting reactants and products, and the solid organic acid catalyst has a water-repellent effect, can quickly and cleanly remove the water generated by the reaction, and greatly improves the reaction conversion rate and yield.

[0040] 4. In the method for preparing isonicotinic acid ester with high conversion rate provided by the present invention, the reaction components are simple and a solid organic acid catalyst is used. On the one hand, it reduces the environmental pollution caused by liquid acid catalysts such as sulfuric acid, and on the other hand, it makes the product easy to separate and can simplify the production process. Detailed implementation mode

[0041] The present invention will be described below in conjunction with specific implementation schemes. It should be noted that the following examples are examples of the present invention, only for illustrating the present invention, and not for limiting the present invention. Other combinations and various improvements within the concept of the present invention can be made without departing from the gist or scope of the present invention.

[0042] The commercially available solid acid catalyst is a sulfuric acid / zirconia solid acid catalyst purchased from Qinzhou Yamei Chemical Co., Ltd.; the commercially available cation exchange resin is D001 macroporous cation exchange resin purchased from Langfang Xingnuo Thermal Insulation Materials Co., Ltd.; the remaining reagents and equipment are conventional reagents and equipment in the technical field.

[0043] Preparation of strongly acidic cation exchange resin

[0044] The strongly acidic cation exchange resin is prepared by the following steps:

[0045] (1) In a four-necked flask equipped with a stirrer, thermometer, reflux condenser and nitrogen protection device, add 0.02 mol of N-(glycidyl)-N-phenyl-epoxyethanemethylamine and 100 mL of anhydrous ethanol, stir and mix evenly, and under nitrogen protection, heat up to 40 °C, then slowly dropwise add 0.022 mol of allyl bromide, the dropping time is 3 hours. After the dropping is completed, heat up to 50 °C, keep the temperature for reaction for 18 hours, then remove the solvent, and obtain Compound B after recrystallization;

[0046] Mass spectrometry data of Formula B: The product was analyzed by LC-MS, and the m / z of the product was 246.15 (100.0%), 247.18 (17.2%), 248.15 (1.5%).

[0047] (2) In a four-necked flask equipped with a stirrer, thermometer and reflux condenser, add 0.01 mol of divinylbenzene, 0.022 mol of Compound B and 0.05 g of benzoyl peroxide, stir evenly, heat up to 90 °C for reaction for 6 hours, then cool to room temperature, filter, wash and dry to obtain Compound C;

[0048] (3) In a four-necked flask equipped with a stirrer, thermometer and reflux condenser, add 10 g of Compound C and 100 mL of tetrahydrofuran to swell for 8 - 12 hours, then add 5 g of sodium sulfamate and 20 mL of 40% sodium hydroxide aqueous solution, heat up to 90 °C, keep the temperature for reaction for 24 hours, then cool to room temperature, filter, wash and dry to obtain the said strongly acidic cation exchange resin.

[0049] Preparation of solid organic acid catalyst - 1

[0050] The solid organic acid catalyst - 1 was prepared through the following steps:

[0051] In a reactor, 5 g of strongly acidic cation exchange resin and 1 g of aluminum chloride were added to 50 mL of absolute ethanol, the temperature was raised to 90 °C, after holding the temperature for reaction for 24 hours, it was cooled to room temperature, filtered, washed, and dried to obtain the solid organic acid catalyst - 1.

[0052] Preparation of solid organic acid catalyst - 2

[0053] Basically the same as the preparation of solid organic acid catalyst - 1, the difference is that the strongly acidic cation exchange resin was replaced with an equal amount of commercially available cation exchange resin.

[0054] Example 1

[0055] The isonicotinic acid ester was prepared through the following steps:

[0056] (1) Under nitrogen protection, 0.2 mol of isonicotinic acid, 0.3 mol of lauryl alcohol and 2 g of solid organic acid catalyst - 1 were added to a 1 L four - necked flask equipped with a stirrer, a reflux condenser and a dropping funnel;

[0057] (2) 4A molecular sieve as a water - carrying agent accounting for 1 / 3 of the volume of the water separator was added to the water separator, the system was heated to 150 °C and reacted for 6 hours;

[0058] (3) After the reaction was completed, the reaction solution was filtered, the filter cake was isonicotinic acid and the solid organic acid catalyst which could be used for recovery and recycling. The filtrate was first washed with 20% sodium carbonate solution until weakly alkaline, then washed with water until the wash water was neutral, allowed to stand for stratification, and the upper organic layer was distilled under reduced pressure until there was no distillate in the distiller to remove excess higher - carbon alcohols and water, thus obtaining the isonicotinic acid ester.

[0059] Example 2

[0060] Basically the same as Example 1, the difference is that 4A molecular sieve was replaced with an equal amount of 5A molecular sieve.

[0061] Example 3

[0062] Basically the same as Example 1, the difference is that lauryl alcohol was replaced with an equimolar amount of n - octanol.

[0063] Comparative Example 1

[0064] Basically the same as Example 1, the difference is that solid organic acid catalyst - 1 was replaced with an equal amount of concentrated sulfuric acid with a mass fraction of 95%.

[0065] Comparative Example 2

[0066] Basically the same as Example 1, the difference is that 4A molecular sieve in the water separator was replaced with an equal volume of benzene.

[0067] Comparative Example 3

[0068] Basically the same as Example 1, the difference is that the solid organic acid catalyst -1 is replaced with an equal amount of commercially available solid acid catalyst.

[0069] Comparative Example 4

[0070] Basically the same as Example 1, the difference is that the solid organic acid catalyst -1 is replaced with an equal amount of cation exchange resin -1.

[0071] Comparative Example 5

[0072] Basically the same as Example 1, the difference is that the solid organic acid catalyst -1 is replaced with an equal amount of solid organic acid catalyst -2.

[0073] Performance test

[0074] Conversion rate and yield detection: Detect the conversion rate of isonicotinic acid and the content of isonicotinic acid ester in the product during the reactions of Examples 1-3 and Comparative Examples 1-5.

[0075] Reaction conversion rate (%) Isonicotinate content in the product (%) Example 1 98 99 Example 2 98 99 Example 3 98 99 Comparative Example 1 69 87 Comparative Example 2 95 96 Comparative Example 3 76 93 Comparative Example 4 93 96 Comparative Example 5 85 95

[0076] According to the comparison of the detection results of Examples 1-3 and Comparative Examples 1-3, for the method for preparing isonicotinic acid ester with high conversion rate provided by the present invention, by using a solid organic acid catalyst and a molecular sieve water-carrying agent, the conversion rate of isonicotinic acid and the selectivity for the reaction of isonicotinic acid ester can be significantly improved.

[0077] According to the comparison of the detection results of Examples 1-3 and Comparative Examples 4 and 5, in the method for preparing isonicotinic acid ester with high conversion rate provided by the present invention, a solid organic acid catalyst is used. Among them, the strong acidic cation exchange resin, based on the multi-sulfonic acid groups in its structure and combined with metal chlorides, has excellent catalytic ability and high selectivity for the reaction of isonicotinic acid ester, and can effectively improve the conversion rate of isonicotinic acid ester.

[0078] The above embodiments are only for illustrating the technical concept and characteristics of the present invention, and the purpose is to enable those who are familiar with this technology to understand the content of the present invention and implement it. It should not be used to limit the protection scope of the present invention. Any equivalent changes or modifications made according to the spirit of the present invention should be covered within the protection scope of the present invention.

Claims

1. A method for preparing isonicotinate, characterized in that, It comprises the following steps: (1) Under nitrogen protection, isonicotinic acid, a polyhydric alcohol, and a solid organic acid catalyst are added to a reactor; (2) The reactor is heated to 110 - 180 °C and reacted for 4 - 6 hours. During the reaction, the water generated is separated by a water separator; (3) After the reaction ends, the product is filtered, neutralized, and distilled under reduced pressure to obtain the isonicotinic acid ester; The water separator contains a water-carrying agent; The solid organic acid catalyst comprises a strongly acidic cation exchange resin and a metal chloride; The strongly acidic cation exchange resin has the structure shown in Formula A below: ， where n = 60 - 180; The metal chloride is selected from one of aluminum chloride, ferric chloride, or chromium chloride; The polyhydric alcohol is lauryl alcohol or n-octanol.

2. The preparation method of the isonicotinic acid ester according to claim 1, characterized in that, In step (1), the molar ratio of isonicotinic acid to the polyhydric alcohol is 1:1 - 1.

5.

3. The preparation method of isonicotinic acid ester according to claim 1, characterized in that, In step (1), the addition amount of the solid organic acid is 3 - 5% of the total mass of the reactants.

4. The method for preparing isonicotinate according to claim 1, characterized in that, The water-carrying agent is selected from one of 4A molecular sieve or 5A molecular sieve.

5. The preparation method of isonicotinic acid ester according to claim 1, characterized in that, The mass ratio of the strongly acidic cation exchange resin to the metal chloride is 3 - 5:

1.

6. The method for preparing isonicotinic acid ester according to claim 1, wherein, The strongly acidic cation exchange resin is prepared through the following steps: (1) In a reactor, N-(glycidyl)-N-phenyl-oxiranemethanamine and an organic solvent are added, stirred and mixed evenly. After heating to 35 - 45 °C under nitrogen protection, allyl bromide is slowly added dropwise over 2 - 3 hours. After the addition is complete, the temperature is raised to 50 - 55 °C and kept warm for reaction for 18 - 24 hours. Then the solvent is removed, and after recrystallization, the compound shown in Formula B below is obtained: ； (2) In a reactor, divinylbenzene, the compound of Formula B, and an initiator are added, stirred evenly, then heated to 80 - 95 °C for reaction for 4 - 6 hours, and then cooled to room temperature. After suction filtration, washing, and drying, the compound shown in Formula C below is obtained: , where n = 60 - 180; (3) In a reactor, the compound of Formula C is added and swollen in tetrahydrofuran for 8 - 12 hours. Then sodium sulfamate and an aqueous sodium hydroxide solution are added, and the temperature is raised to 80 - 100 °C and kept warm for reaction for 16 - 24 hours. After cooling to room temperature, suction filtration, washing, and drying are carried out to obtain the strongly acidic cation exchange resin.

7. The method for preparing isonicotinate according to claim 6, characterized in that, In step (1), the molar ratio of N-(glycidyl)-N-phenyl-oxiranemethanamine to allyl bromide is 1:1 - 1.

2.

8. The method for preparing isonicotinic acid ester according to claim 6, characterized in that, In step (2), the initiator is selected from one of benzoyl peroxide, tert-butyl peroxybenzoate, or methyl ethyl ketone peroxide; the molar ratio of divinylbenzene to the compound of Formula B is 1:2 - 2.

2.

9. The preparation method of isonicotinic acid ester according to claim 6, characterized in that, In step (3), the mass ratio of the compound of Formula C to sodium sulfamate is 2 - 3:

1.

10. The method for preparing isonicotinic acid ester according to claim 1, characterized in that, The preparation method of the solid organic acid catalyst is: In a reactor, the strongly acidic cation exchange resin and the metal chloride are added to an organic solvent, heated to 80 - 90 °C, kept warm for reaction for 16 - 24 hours, and then cooled to room temperature. After suction filtration, washing, and drying, the solid organic acid catalyst is obtained.

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