Preparation method of niacin polyhydroxy ester

Abstract

The invention belongs to the technical field of preparation of niacin polyhydroxy alcohol ester, particularly relates to a method for preparing inositol nicotinate in the presence of 1-alkyl imidazole, and particularly relates to a method for preparing niacin polyhydroxy ester by reacting polyhydroxy alcohol and niacin in ionic liquid of 1-alkyl imidazole. The niacin polyhydroxy ester prepared by the method, especially the inositol nicotinate, can be obtained as a colorless product, so that the final purification of the product is greatly simplified. According to the method disclosed by the invention, the inherent strong pungent smell of pyridine in a pyridine process is avoided, and the friendliness of an operation environment is improved. According to the method of the invention, the process can be carried out intermittently, semi-continuously or continuously.

Description

[0001] This application claims priority to a U.S. patent application filed with the U.S. Patent Office on March 22, 2024, with application number US18 / 614,226 and invention title "PROCESS FOR PRODUCING POLYHYDROXY ESTERS OF NICOTINIC ACID", the entire content of which is incorporated herein by reference. TECHNICAL FIELD

[0002] The present invention belongs to the technical field of preparing polyhydroxy esters of nicotinic acid, and particularly relates to a method for preparing inositol nicotinate in the presence of 1-alkylimidazole. BACKGROUND ART

[0003] Polyhydroxy esters of nicotinic acid are important derivatives of nicotinic acid (i.e., vitamin B3) and are essential components for human health and animal nutrition. Two commercially important esters are inositol nicotinate (I) and sorbitol nicotinate (II), and their chemical formulas are as follows:

[0004]

[0005] Inositol nicotinate combines the effects of inositol in promoting fat metabolism and reducing blood lipids in the liver and tissues, as well as the effect of nicotinic acid in dilating peripheral blood vessels. Inositol nicotinate also has a wide range of therapeutic applications and is an ideal drug for treating hyperlipidemia, Raynaud's disease, and intermittent claudication. It can also effectively treat cardiovascular diseases and various peripheral vascular diseases.

[0006] Since inositol nicotinate is slowly hydrolyzed into inositol and nicotinic acid in the body and has a sustained-release effect, it can be used to overcome the adverse effects of long-term administration of nicotinic acid. In fact, inositol nicotinate has been widely used as a non-allergenic nutritional supplement for nicotinic acid.

[0007] There are many methods for synthesizing nicotinic acid esters, and these methods for synthesizing inositol nicotinate can be roughly divided into two types.

[0008] The first method involves forming nicotinoyl chloride as an intermediate with the aid of an activator, and then it reacts with inositol to form the product of inositol nicotinate of formula (I) in two steps, as shown in the following reaction formula:

[0009]

[0010] The second method involves directly esterifying nicotinic acid with inositol in one step with an activator, as shown in the following reaction formula:

[0011]

[0012] US 3,557,130 discloses a method for preparing a colorless ester of pyridinecarboxylic acid. In this method, pyridinecarboxylic acid, especially nicotinic acid, is suspended in pyridine and reacted with phosphorus oxychloride to form nicotinyl chloride, which is then reacted with inositol to form inositol nicotinate. Subsequently, the reaction mixture is poured into water to precipitate the product, which is then filtered and washed with water and acetone or alcohol to isolate the product.

[0013] GB 932,079 discloses a method for preparing sorbitol nicotinate, in which nicotinyl chloride hydrochloride and sorbitol are reacted in pyridine, and the product is separated by precipitation from water.

[0014] EP 0019260 discloses a method for preparing D-glucitol nicotinate, which is sorbitol nicotinate, in which nicotinic acid is reacted with D-glucitol in the presence of phosphorus oxychloride and pyridine, using nicotinamide as a catalyst.

[0015] CN 102964298 A discloses a method for preparing mannitol nicotinate. Nicotinic acid in pyridine is reacted with thionyl chloride to form nicotinyl chloride, which is then reacted with mannitol to form hexanicotinic acid mannitol ester. After purification with dilute acid, a product with a yield of about 66% is obtained.

[0016] CN 103819399 B discloses a method for preparing hexanicotinic acid mannitol. Nicotinic acid in pyridine is reacted with phosphorus oxychloride to form nicotinyl chloride, which is then reacted with mannitol to form hexanicotinic acid mannitol, with a yield of 68.4%. After purification, the total yield of hexanicotinic acid mannitol drops to 50.2%.

[0017] The methods disclosed in the prior art above always produce wastewater containing pyridine and by-products. CN102627601B discloses an improved method for recovering pyridine in the production of inositol nicotinate. This method distills pyridine from the aqueous solution by adding sodium hydroxide, and repeatedly dries it with solid sodium hydroxide, and finally distills it.

[0018] These methods have no particular advantages because they use pyridine to scavenge bases and as a solvent. Pyridine has a foul odor, and its use as a solvent causes environmental hazards and occupational problems.

[0019] CN 1546676A discloses an enzymatic method for producing inositol nicotinate, which uses anhydrous tert-butanol as a solvent for the reaction of nicotinic acid and inositol in the presence of Novozyme 435. However, this reaction is carried out in a highly diluted solution of inositol (1 - 2 mmol, 0.18 g - 0.36 g / L) and nicotinic acid (6 mmol, 0.74 g / L) in the presence of a large amount of lipase (5 g / L). Such a highly diluted solution and a large amount of enzyme are not conducive to industrial production applications.

[0020] CN 113493409 A attempts to overcome these drawbacks and discloses a method for producing inositol nicotinate and sorbitol nicotinate without involving pyridine. In this method, carbonyl diimidazole reacts with nicotinic acid in an aprotic solvent to form an intermediate nicotinoyl imidazole, which then condenses with inositol to form the product. Although this method can be carried out without pyridine, the use of carbonyl diimidazole also has its own unique industrial challenges. First, the cost of carbonyl diimidazole is very high; second, the by-product imidazole is difficult to recover; third, this method requires the use of a large amount of organic solvents. Therefore, this method is not economically feasible. Summary of the Invention

[0021] One object of the present invention is to disclose a method for preparing polyhydroxy esters of nicotinic acid to improve the drawbacks of known methods.

[0022] Another object of the present invention is to avoid the use of pyridine as a reaction solvent in the preparation of polyhydroxy esters of nicotinic acid.

[0023] The present invention provides a method for producing polyhydroxy esters of nicotinic acid, which includes reacting a polyhydroxy alcohol with nicotinic acid in the presence of a 1-alkylimidazole having the structure shown in Formula I by using an activator to obtain a polyhydroxy ester of nicotinic acid;

[0024]

[0025] wherein, R1 may be a straight-chain, branched-chain or substituted C1-C 12 alkyl or aryl; R2, R3 and R4 are independently of each other a hydrogen atom, or a straight-chain, branched-chain or substituted C1-C 12 alkyl or aryl.

[0026] When producing polyhydroxy esters of nicotinic acid, using 1-alkylimidazole has the following obvious advantages compared to using pyridine:

[0027] 1. Nicotinic acid can form a clear solution in 1-alkylimidazole, while it forms a thick suspension in pyridine. Compared with a solid suspension, the operation of a solution is more convenient.

[0028] 2. By selecting an appropriate reaction temperature, 1-alkylimidazole hydrochloride can be maintained in an ionic liquid state, thereby improving the fluidity of the reaction mixture. The melting point of pyridine hydrochloride is 145-147 °C, which is much higher than its boiling point of 115 °C, resulting in its precipitation in the reaction mixture in the form of crystalline solids, increasing the processing difficulty.

[0029] 3. The polyhydroxy esters of nicotinic acid obtained by this method, especially inositol nicotinate, can be obtained as a colorless product, thus greatly simplifying the final purification of the product. The method of the present invention avoids the strong pungent odor of pyridine inherent in the pyridine process and improves the environmental friendliness of the operation environment.

[0030] 4. According to the method of the present invention, the process can be carried out intermittently, semi - continuously or continuously. Detailed implementation mode

[0031] The present invention relates to a method for producing polyhydroxy esters of nicotinic acid. Specifically, the present invention relates to a method for preparing polyhydroxy esters of nicotinic acid without using pyridine as a reaction solvent.

[0032] The present invention is achieved by carrying out an esterification reaction of a polyhydroxy alcohol with nicotinic acid or its derivative using an activator in the presence of a 1 - alkylimidazole having the structure shown in formula I:

[0033]

[0034] Among them, R1 can be a straight - chain, branched - chain, cyclic or substituted C1 - C 12 alkyl or aryl group; R2, R3 and R4 are each independently a hydrogen atom, or a straight - chain, branched - chain, cyclic or substituted C1 - C 12 alkyl or aryl group.

[0035] Exemplary "alkyl" groups include methyl, ethyl, propyl, isopropyl, cyclopropyl, n - butyl, tert - butyl, isobutyl, cyclobutyl, cyclopropylmethyl, pentyl, isopentyl, hexyl, isohexyl, heptyl, 4,4 - dimethylpentyl, octyl, 2,2,4 - trimethylpentyl, nonyl, decyl, undecyl, dodecyl, 2 - methoxyethyl, 2 - ethoxyethyl, 3 - methoxypropyl, 3 - ethoxypropyl, 2 - dimethylaminoethyl, 3 - dimethylaminopropyl, 2 - chloroethyl, 3 - chloropropyl, etc.

[0036] Exemplary "aryl" groups include phenyl, substituted phenyl, naphthyl, substituted naphthyl, pyridyl, substituted pyridyl, etc.

[0037] Preferably, the present invention is achieved by carrying out an esterification reaction of a polyhydroxy alcohol with nicotinic acid or its derivative using an activator in a 1 - alkylimidazole ionic liquid having the structure shown in formula I:

[0038]

[0039] Among them, R1 can be a straight - chain, branched - chain, cyclic or substituted C1 - C 12 alkyl or aryl group; and R2, R3 and R4 can each independently be a hydrogen atom, or a straight - chain, branched - chain, cyclic or substituted C1 - C 12 alkyl or aryl group.

[0040] More preferably, the 1 - alkylimidazole is selected from the following compounds: 1 - methylimidazole, 1 - ethylimidazole, 1 - propylimidazole, 1 - butylimidazole, 1 - isobutylimidazole, or a mixture of multiple of any of the foregoing substances.

[0041] The polyhydric alcohol is selected from the following compounds: inositol, sorbitol (also known as D-sorbitol), mannitol, glycerol, xylitol, pentaerythritol, or a mixture of any of the foregoing substances. Preferably, the polyhydric alcohol is inositol, and the resulting product is inositol nicotinate.

[0042] The nicotinic acid polyhydric ester is formed by the action of an activator. Suitable activators are selected from the following compounds: phosphorus oxychloride, phosphorus trichloride, phosphorus pentachloride, thionyl chloride, sulfuryl dichloride, phosgene, dichlorophosgene, triphosgene, alkylsulfonyl chloride, arylsulfonyl chloride, or a mixture of any of the foregoing substances. The alkylsulfonyl chloride may be a C1-C 12 linear, cyclic or branched alkylsulfonyl chloride; the arylsulfonyl chloride may be benzenesulfonyl chloride or substituted benzenesulfonyl chloride, naphthalenesulfonyl chloride or substituted naphthalenesulfonyl chloride, pyridinesulfonyl chloride, or a mixture of any of the foregoing substances.

[0043] Surprisingly and unexpectedly, nicotinic acid can form a salt with 1-alkylimidazole with low melting point, which has the characteristics of ionic liquid. Even more unexpectedly, the ionic liquid can be miscible with 1-alkylimidazole and form a homogeneous solution. The ionic liquid solution can be preferentially used in the esterification reaction of nicotinic acid and polyhydric alcohol to produce nicotinic acid polyhydric ester.

[0044] In the method of the present invention, the esterification reaction can be carried out by mixing the reactants in any order in 1-alkylimidazole. Preferably, the reaction can be carried out by mixing nicotinic acid with 1-alkylimidazole to form an ionic liquid solution, and then adding an activator to generate nicotinyl chloride or a mixed anhydride of nicotinic acid and sulfonic acid as an intermediate. After the intermediate is formed, polyhydric alcohol is added to produce nicotinic acid polyhydric ester.

[0045] More preferably, the esterification reaction can be carried out by mixing nicotinic acid and polyhydric alcohol in 1-alkylimidazole, and then adding an activator to react to produce nicotinic acid polyhydric ester.

[0046] In addition, nicotinyl chloride hydrochloride (an activated derivative of nicotinic acid) can react with polyhydric alcohol in 1-alkylimidazole to produce nicotinic acid polyhydric ester. In this case, adding an activator is not necessary, but an activator can be selectively added to ensure the complete progress of the reaction.

[0047] In this reaction, the dosage of 1-alkylimidazole is not limited relative to the dosage of polyhydric alcohol or nicotinic acid. Preferably, 1-alkylimidazole is used both to form an ionic liquid with nicotinic acid and as a reaction solvent. In addition, 1-alkylimidazole can also be used as an acid scavenger to neutralize the acid released by the activator during the esterification reaction. The acid released from the activator can be hydrochloric acid, alkylsulfonic acid or arylsulfonic acid.

[0048] The method of the present invention has an additional advantage that 1-alkylimidazole can form an ionic liquid with the acid (such as hydrochloric acid, methanesulfonic acid, benzenesulfonic acid or p-toluenesulfonic acid) released by the activator during the esterification reaction. Compared with the crystalline solid forming pyridinium salt, the ionic liquid formed in the method of the present invention can improve the fluidity of the reaction mixture, enhance heat transfer, and improve the generation of local overheating phenomenon.

[0049] In some cases, using an aprotic solvent can further improve the fluidity of the reactants and products in the reaction mixture. Suitable aprotic solvents can be selected from the following compounds: C3-C 12 ketones, C2-C 12 nitriles, esters, ethers, amides, dialkyl carbonates, sulfoxides, sulfones, haloalkanes, aliphatic compounds, haloarenes and arenes; wherein, the alkyl is C1-C 12 , the halogen is fluorine, chlorine, bromine or a mixture of any of the foregoing halogens, and the arene is selected from phenyl, naphthalene and their substituted derivatives. Preferred aprotic solvents are toluene or xylene.

[0050] The temperature range of the esterification reaction can be between 10°C and 150°C. Preferably, the reaction temperature is between 20°C and 100°C. More preferably, the reaction temperature range is 30°C to 90°C. Most preferably, the reaction temperature range is 40°C to 80°C.

[0051] After the esterification reaction is completed, any suitable method can be used to separate the polyhydroxy ester of nicotinic acid. Preferably, the reaction mixture is diluted with water to precipitate the ester product, and extraction is carried out by solid-liquid separation. After washing with water, a colorless product can be obtained.

[0052] Based on the molar amount of the polyhydroxy alcohol, the yield of the polyhydroxy ester of nicotinic acid can reach at least 85%, preferably at least 90%, more preferably at least 95%.

[0053] In order to further reduce the residual 1-alkylimidazole in the separated product, it is found that the solid product can be washed with a dilute acid solution. The acid can be selected from inorganic acids, organic carboxylic acids or a mixture of any of the foregoing substances. Suitable inorganic acids include hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, phosphorous acid and a mixture of any of the foregoing substances. Suitable organic carboxylic acids include formic acid, acetic acid, propionic acid, butyric acid, glycolic acid, oxalic acid, malic acid, tartaric acid, citric acid, fumaric acid, maleic acid, succinic acid, malonic acid and a mixture of any of the foregoing substances.

[0054] After separating the polyhydroxy ester of nicotinic acid, the mother liquor contains the salt of 1-alkylimidazole. The 1-alkylimidazole in the mother liquor can be recovered by any method known to those skilled in the art, such as distillation or extraction, and can be reused in the production of the polyhydroxy ester of nicotinic acid.

[0055] When alkylsulfonyl chlorides or arylsulfonyl chlorides are used in the esterification reaction, the 1-alkylimidazolium salts of the corresponding alkylsulfonic acids or arylsulfonic acids can be converted to their alkali metal salts by reaction with alkaline hydroxides, where the alkali metal can be lithium, sodium, potassium, or a mixture of any of the foregoing alkali metals. The resulting alkali metal sulfonates can be easily recovered from the aqueous solution by concentration and crystallization and can be converted to the corresponding sulfonyl chlorides by any method known to those skilled in the art.

[0056] Needless to say, the polyhydroxy esters of nicotinic acid produced by the method of the present invention do not contain detectable amounts of pyridine because pyridine is not used throughout the process. On the other hand, the polyhydroxy ester products of nicotinic acid produced by the method of the present invention may contain trace amounts of 1-alkylimidazole.

[0057] When producing polyhydroxy esters of nicotinic acid, using 1-alkylimidazole has the following obvious advantages compared to using pyridine:

[0058] 1. Nicotinic acid forms a clear solution in 1-alkylimidazole, while it forms a thick suspension in pyridine. The operation of a solution is more convenient compared to a solid suspension.

[0059] 2. By selecting a suitable reaction temperature, 1-alkylimidazole hydrochloride can be maintained in an ionic liquid state, thus improving the fluidity of the reaction mixture. The melting point of pyridine hydrochloride is 145 - 147 °C, which is much higher than its boiling point of 115 °C, resulting in its precipitation as a crystalline solid in the reaction mixture and increasing the processing difficulty.

[0060] 3. The polyhydroxy esters of nicotinic acid prepared by this method, especially inositol nicotinate, can be obtained as colorless products, thus greatly simplifying the final purification of the product. The method of the present invention avoids the strong pungent odor of pyridine inherent in the pyridine process and improves the friendliness of the operating environment.

[0061] 4. According to the method of the present invention, the process can be carried out batchwise, semi - continuously, or continuously.

[0062] The following examples will illustrate the embodiments of the present invention but are not intended to limit its scope of application.

[0063] Example 1

[0064] 12.3 g of nicotinic acid and 8.2 g of 1 - methylimidazole were added to a 50 mL round - bottom flask. The mixture was heated to 82 °C to form a clear solution. When cooled to 75 °C, crystalline salts began to appear. After further cooling, a crystalline solid was formed. 4.5 g of 1 - methylimidazole was added to this solid and heated to about 40 °C to form a clear solution.

[0065] Example 2

[0066] Add 80 g of 1-methylimidazole, 9 g of inositol, and 42 g of nicotinic acid to a 500 mL round-bottom flask. Stir the mixture and heat it to 35 °C. While stirring, slowly add 45 mL of benzenesulfonyl chloride dropwise, allowing the temperature to rise to 80 - 85 °C. After continuing to stir at this temperature for 30 minutes, add 200 mL of deionized water to the flask to precipitate the crystalline solid product.

[0067] Stir the suspension and cool it to 20 °C, then filter and wash it thoroughly with deionized water to obtain a colorless crystalline product. After drying, 40.0 g of inositol nicotinate is obtained, and the molar yield calculated based on inositol is 98.8%.

[0068] Example 3

[0069] Add 25 g of 1-butylimidazole, 1.8 g of inositol, and 9 g of nicotinic acid to a 250 mL round-bottom flask. Stir the mixture at 14 °C and slowly add 9 mL of benzenesulfonyl chloride dropwise while allowing the temperature to rise to 80 - 85 °C. After continuing to stir at this temperature for 30 minutes, add 75 mL of deionized water to the flask to precipitate the crystalline solid product.

[0070] Stir the suspension and cool it to 20 °C, then filter and wash it thoroughly with deionized water to obtain a colorless crystalline product. After drying, 7.8 g of inositol nicotinate is obtained, and the molar yield calculated based on inositol is 96.2%.

[0071] Example 4

[0072] Add 23 g of 1-methylimidazole, 1.82 g of sorbitol, and 9 g of nicotinic acid to a 250 mL round-bottom flask. Stir the mixture at 11 °C and slowly add 5.4 mL of methanesulfonyl chloride dropwise while allowing the temperature to rise to 80 - 85 °C. After continuing to stir at this temperature for 30 minutes, add 75 mL of deionized water to the flask to precipitate the crystalline solid product.

[0073] Stir the suspension and cool it to 20 °C, then filter and wash it with a large amount of deionized water to obtain a colorless crystalline product. After drying, 7.9 g of sorbitol nicotinate is obtained, and the molar yield calculated based on sorbitol is 97.2%.

[0074] Example 5

[0075] Add 115 g of 1-propylimidazole, 9 g of inositol, and 42 g of nicotinic acid to a 500 mL round-bottom flask. Stir the mixture and heat it to 30 °C. While stirring, slowly add 45 mL of benzenesulfonyl chloride dropwise and allow the temperature to rise to 80 - 85 °C. After continuing to stir at this temperature for 30 minutes, add 200 mL of deionized water to the flask to precipitate the crystalline solid product. Stir the suspension and cool it to 20 °C, then filter and wash it thoroughly with deionized water to obtain a colorless crystalline product. After drying, 40.0 g of inositol nicotinate is obtained, and the molar yield calculated based on inositol is 98.8%.

[0076] Example 6

[0077] Add 50 g of 1-ethylimidazole, 3.6 g of inositol, and 18 g of nicotinic acid to a 250 mL round-bottom flask. Stir the mixture at 14 °C and add 13 g of triphosgene while allowing the temperature to rise to 80 - 85 °C. After continuing to stir at this temperature for 30 minutes, add 150 mL of deionized water to the flask to precipitate the solid product. Stir the suspension and cool it to 20 °C, then filter and wash it thoroughly with deionized water to obtain a crystalline product. After drying, 12.5 g of inositol nicotinate is obtained, and the molar yield calculated based on inositol is 77.2%.

[0078] Example 7

[0079] Add 42 g of 1-ethylimidazole, 3.6 g of inositol, and 18.2 g of nicotinic acid to a 250 mL round-bottom flask. Stir the mixture at 24 °C and add 6.8 mL of phosphorus oxychloride while allowing the temperature to rise to 80 - 85 °C. After continuing to stir at this temperature for 30 minutes, add 150 mL of deionized water to the flask to precipitate the solid product. Stir the suspension and cool it to room temperature, then filter and wash it thoroughly with deionized water to obtain a crystalline product. After drying, 12.3 g of inositol nicotinate is obtained, and the molar yield calculated based on inositol is 75.9%.

[0080] Example 8

[0081] Add 42 g of 1-ethylimidazole and 18.2 g of nicotinic acid to a 250 mL round-bottom flask. Stir the mixture at 20 °C and add 10.2 mL of thionyl chloride while allowing the temperature to rise to 60 - 70 °C. After continuing to stir at this temperature for 2 hours, gradually add 3.6 g of inositol and maintain the temperature at 60 - 70 °C. After the addition is complete, raise the temperature to 80 °C and maintain it for 2 hours. Subsequently, add 150 mL of deionized water to the flask to precipitate the solid product. After stirring and cooling to room temperature, filter the suspension and wash it thoroughly with deionized water to obtain a crystalline product. After drying, 12.6 g of inositol nicotinate is obtained, and the molar yield calculated based on inositol is 77.8%.

[0082] Example 9

[0083] 42 g of 1-ethylimidazole, 3.6 g of inositol and 18.2 g of nicotinic acid were added to a 250 mL round-bottom flask. The mixture was stirred at 20 °C, and 26.7 g of p-toluenesulfonyl chloride was added while the temperature was raised to 80 - 85 °C. After stirring at this temperature for 30 minutes, 150 mL of deionized water was added to the flask to precipitate the crystalline solid product. After the suspension was stirred and cooled to room temperature, it was filtered and washed with a large amount of deionized water to obtain a colorless crystalline product. After drying, 15.9 g of inositol nicotinate was obtained, and the molar yield calculated based on inositol was 98.1%.

[0084] Example 10

[0085] 23 g of 1-methylimidazole, 1.82 g of mannitol and 9 g of nicotinic acid were added to a 250 mL round-bottom flask. The mixture was stirred at 23 °C, and 5.4 mL of methanesulfonyl chloride was slowly added dropwise while the temperature was raised to 80 - 85 °C. After stirring at this temperature for 30 minutes, 75 mL of deionized water was added to the flask to precipitate the crystalline solid product. After the suspension was stirred and cooled to 20 °C, it was filtered and washed thoroughly with deionized water to obtain a colorless crystalline product. After drying, 7.8 g of mannitol nicotinate was obtained, and the molar yield calculated based on mannitol was 96.1%.

[0086] Example 11

[0087] 21 g of 1-methylimidazole, 15 g of toluene, 1.8 g of inositol and 9.2 g of nicotinic acid were added to a 250 mL round-bottom flask. The mixture was stirred at 8 °C, and 8.9 mL of benzenesulfonyl chloride was slowly added dropwise while the temperature was raised to 80 - 85 °C. After stirring at this temperature for 30 minutes, 75 mL of deionized water was added to the flask to precipitate the crystalline solid product. After the suspension was stirred and cooled to 20 °C, it was filtered and washed with a large amount of deionized water to obtain a colorless crystalline product. After drying, 7.9 g of inositol nicotinate was obtained, and the molar yield calculated based on inositol was 97.5%.

[0088] It should be understood that the above examples and descriptions are only for demonstrating the present invention and do not constitute a limitation on its scope. Those skilled in the art can make various modifications and adjustments according to the principles of the present invention, and these modifications should be included within the gist and scope of this application and be protected by the appended claims.

Claims

1. A method for producing nicotinic acid polyol esters, comprising: In the presence of 1-alkylimidazole having a structure shown in Formula I, using an activator to react polyhydroxy alcohol with nicotinic acid to obtain nicotinic acid polyhydroxy ester; Wherein R1 is a straight chain, branched chain or substituted C1-C 12 R2, R3 and R4 are independently a hydrogen atom, or a linear, branched or substituted C1-C 12 Alkyl or aryl.

2. The method according to claim 1, characterized in that The polyhydric alcohol is selected from the following compounds: inositol, sorbitol, mannitol, glycerol, erythritol, or any mixture of the foregoing substances.

3. The method according to claim 1, characterized in that The activator is selected from at least one of the following compounds: phosphorus oxychloride, phosphorus trichloride, phosphorus pentachloride, thionyl chloride, thionyl dichloride, phosgene, diphosgene, triphosgene, alkyl sulfonyl chloride, or any mixture of the foregoing substances.

4. The method according to claim 1, characterized in that: 1-Alkyl imidazole includes 1-methyl imidazole, 1-ethyl imidazole, 1-propyl imidazole, 1-butyl imidazole, 1-isobutyl imidazole, or a mixture of any of the foregoing.

5. The method according to claim 1, characterized in that C1-C 12 The alkyl group includes methyl, ethyl, propyl, isopropyl, cyclopropyl, n-butyl, tert-butyl, isobutyl, cyclobutyl, cyclopropylmethyl, pentyl, isopentyl, hexyl, isohexyl, heptyl, 4,4-dimethylpentyl, octyl, 2,2,4-trimethylpentyl, nonyl, decyl, undecyl, dodecyl, 2-methoxyethyl, 2-ethoxyethyl, 3-methoxypropyl, 3-ethoxypropyl, 2-dimethylaminoethyl, 3-dimethylaminopropyl, 2-chloroethyl or 3-chloropropyl.

6. The method according to claim 1, characterized in that The temperature for the reaction of the polyhydric alcohol and nicotinic acid is 10°C to 150°C.

7. The method according to claim 1, characterized in that The nicotinic acid polyol esters contain no detectable pyridine.

8. The method according to claim 1, characterized in that The nicotinic acid polyol ester contains a trace amount of 1-alkylimidazole.

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