Synthesis method of high-purity nicotinamide

Abstract

The invention relates to the technical field of organic synthesis, and provides a synthesis method of high-purity nicotinamide, which comprises the following steps: S1, uniformly mixing 3-aminomethylpyridine, a catalyst and a first solvent, reacting, filtering and cooling to obtain a nicotinamide crude product; s2, mixing the nicotinamide crude product with a second solvent, cooling and crystallizing to obtain high-purity nicotinamide, the catalyst comprises potassium permanganate and composite manganese oxide in a weight ratio of 1.5: (1-1.5); the composite manganese oxide comprises the following raw materials: water-soluble manganese salt, a titanium source and zirconium dioxide; the first solvent comprises ethanol; the second solvent includes ethanol. According to the technical scheme, the problems of relatively low yield and relatively low purity of nicotinamide in related technologies are solved.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and in particular to a method for synthesizing high-purity nicotinamide. Background Art

[0002] Nicotinamide, a 3-pyridinecarboxamide, is collectively referred to together with niacin as vitamin PP. It appears as white needle-shaped crystals or powder, soluble in water, ethanol, and glycerin. It is an important chemical raw material with a wide range of applications in medicine, food, and cosmetics. In medicine, niacinamide can be used to prevent and treat conditions such as pellagra, stomatitis, and glossitis, and also has cholesterol-lowering and cardiovascular benefits. In the food industry, it can be added to foods as a nutritional supplement. In cosmetics, niacinamide is widely used in various skincare products for its whitening, anti-aging, and moisturizing properties.

[0003] As demand for nicotinamide continues to grow across various industries, the requirements for its purity and yield are also becoming increasingly stringent. Currently, there are several major methods for synthesizing nicotinamide, such as the 3-cyanopyridine hydrolysis method, the ammonium nicotinate dehydration method, and the methylpentanediamine method. However, in practical applications, these methods suffer from low catalytic activity and reaction conversion rates, which easily lead to the production of byproducts during the reaction, ultimately leaving the yield and purity of nicotinamide in need of improvement. Furthermore, some synthesis processes are demanding, requiring high temperatures and high pressures, which not only increases equipment investment and energy consumption but also poses certain safety risks.

[0004] Therefore, a method for synthesizing high-purity nicotinamide is proposed to obtain nicotinamide with high purity and yield, which is of great significance for expanding the scope of use of nicotinamide and meeting people's needs. Summary of the Invention

[0005] The present invention provides a method for synthesizing high-purity nicotinamide, which solves the problems of low nicotinamide yield and low purity in the related art.

[0006] The technical solutions of the present invention are as follows: The present invention provides a method for synthesizing high-purity nicotinamide, comprising the following steps: S1. Evenly mix 3-aminomethylpyridine, a catalyst, and a first solvent, react, filter, and cool to obtain a crude nicotinamide; S2. mixing the crude nicotinamide and a second solvent, cooling and crystallizing, to obtain the high-purity nicotinamide; The catalyst comprises potassium permanganate and composite manganese oxide in a weight ratio of 1.5:1 to 1.5; The raw materials of the composite manganese oxide include water-soluble manganese salt, titanium source and zirconium dioxide; The first solvent includes ethanol; The second solvent includes ethanol.

[0007] As a further technical solution, the water-soluble manganese salt includes one or more of manganese nitrate, manganese sulfate, and manganese chloride, preferably manganese nitrate.

[0008] As a further technical solution, the titanium source includes one or both of an organic titanium source and an inorganic titanium source; The organic titanium source includes one or both of tetraisopropyl titanate and tetraethyl titanate, preferably tetraisopropyl titanate; The inorganic titanium source includes one or both of titanyl sulfate and titanium sulfate, preferably titanyl sulfate.

[0009] As a further technical solution, when the titanium source includes an organic titanium source and an inorganic titanium source, the weight ratio of the organic titanium source to the inorganic titanium source is 1:4.

[0010] In the synthesis method of high-purity nicotinamide of the present invention, when the titanium source includes an organic titanium source and an inorganic titanium source, the organic titanium source and the inorganic titanium source exert a synergistic effect and can be more effectively combined with the zirconium dioxide carrier, thereby improving the success rate of zirconium dioxide loading the titanium source. By adjusting the content ratio of the organic titanium source and the inorganic titanium source, when the weight ratio of the organic titanium source to the inorganic titanium source is 1:4, the adsorption effect of zirconium dioxide on the titanium source is better.

[0011] As a further technical solution, the weight ratio of the zirconium dioxide, the titanium source, and the water-soluble manganese salt is 20:0.5:3~7, for example, it can be 20:0.5:3, 20:0.5:4, 20:0.5:4.5, 20:0.5:5, 20:0.5:5.5, 20:0.5:6, 20:0.5:6.5, 20:0.5:7, and preferably 20:0.5:4~5.

[0012] In the synthesis method of high-purity nicotinamide of the present invention, when the weight ratio of zirconium dioxide, titanium source, and water-soluble manganese salt is 20:0.5:4-5, the yield of nicotinamide can be further improved to 97.44%-97.56%. When the weight ratio of zirconium dioxide, titanium source, and water-soluble manganese salt is outside the range of 20:0.5:4-5, the catalytic effect of the composite manganese oxide is poor, and the effect of improving the yield of nicotinamide is somewhat poor.

[0013] As a further technical solution, the preparation method of the composite manganese oxide comprises the following steps: A1, dissolving the water-soluble manganese salt and titanium source in water and dispersing them uniformly to obtain a mixed solution; A2. Add the zirconium dioxide to the mixed solution, disperse it evenly, concentrate it, dry it, and calcine it to obtain a composite manganese oxide.

[0014] In the preparation process of the composite manganese oxide of the present invention, zirconium dioxide is impregnated with a water-soluble manganese salt and a titanium source. Through a calcination process, the zirconium dioxide carrier is successfully loaded with oxides containing titanium and manganese, thereby successfully obtaining a composite manganese oxide catalyst.

[0015] As a further technical solution, in step A1, when the dispersion is uniform, stirring is adopted, the stirring speed is 500-700 rpm, for example, it can be 500 rpm, 550 rpm, 600 rpm, 650 rpm, 700 rpm, preferably 500 rpm, 600 rpm, 700 rpm, more preferably 600 rpm, and the stirring time is 10-20 min, for example, it can be 10 min, 12 min, 15 min, 16 min, 18 min, 20 min, preferably 10 min, 15 min, 20 min, more preferably 15 min; In step A2, when the dispersion is uniform, stirring is adopted, the stirring speed is 300-400 rpm, for example, it can be 300 rpm, 310 rpm, 350 rpm, 380 rpm, 400 rpm, preferably 300 rpm, 350 rpm, 400 rpm, more preferably 350 rpm, the stirring time is 50-80 min, for example, it can be 50 min, 55 min, 60 min, 65 min, 70 min, 75 min, 80 min, preferably 50 min, 60 min, 80 min, more preferably 60 min; In step A2, during the calcination, the temperature is 350-400°C, for example, it can be 350°C, 360°C, 370°C, 380°C, 390°C, 400°C, preferably 350°C, 400°C, more preferably 350°C, and the time is 1-1.5h, for example, it can be 1h, 1.1h, 1.2h, 1.3h, 1.4h, 1.5h, preferably 1h, 1.5h, more preferably 1.5h.

[0016] As a further technical solution, the second solvent further includes propylene glycol methyl ether acetate; In the second solvent, the weight ratio of ethanol to propylene glycol methyl ether acetate is 4 to 9:1, for example, it can be 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, preferably 4:1, 5:1, 9:1.

[0017] In the synthesis method of high-purity nicotinamide of the present invention, ethanol and propylene glycol methyl ether acetate are used together as crystallization solvents when cooling and crystallizing the crude nicotinamide product, thereby further improving the purity of the nicotinamide. The reason for this may be that, during the process of dissolving the crude nicotinamide product in ethanol, the addition of propylene glycol methyl ether acetate can, to a certain extent, improve the solvent's ability to dissolve impurities in the nicotinamide, and in the subsequent crystallization process, the dissolved impurity components are not easily precipitated, thereby further improving the purity of the nicotinamide. By adjusting the volume ratio of ethanol and propylene glycol methyl ether acetate, when the weight ratio of ethanol to propylene glycol methyl ether acetate is 4 to 9:1, the effect of improving the purity of the nicotinamide is better.

[0018] As a further technical solution, the cooling crystallization is divided into a first stage cooling crystallization and a second stage cooling crystallization; During the first stage of cooling crystallization, the temperature is cooled to 10-15°C at a cooling rate of 4-8°C / min; During the second stage of cooling crystallization, the temperature is cooled to 0-5°C at a cooling rate of 0.5-1.5°C / min.

[0019] In the synthesis method of high-purity nicotinamide of the present invention, a segmented cooling crystallization method is adopted during the cooling crystallization of the crude nicotinamide. By accurately regulating the cooling rates of the two segments and reasonably controlling the crystallization temperature, the purity of the nicotinamide can be improved.

[0020] As a further technical solution, the amount of the catalyst is 20% to 30% of the mass of the 3-aminomethylpyridine, for example, 20%, 22%, 23%, 25%, 26%, 28%, 30%, preferably 20%, 25%, 30%, more preferably 25%; In terms of g / mL, the mass volume ratio of the 3-aminomethylpyridine to the first solvent is 100 g:400-550 mL.

[0021] As a further technical solution, in step S1, the reaction temperature is 45-55° C. and the reaction time is 6-8 hours.

[0022] As a further technical solution, in terms of g / mL, the mass volume ratio of the 3-aminomethylpyridine and the second solvent is 100g:200~300mL, for example, it can be 100g:200mL, 100g:220mL, 100g:250mL, 100g:270mL, 100g:300mL, preferably 100g:200mL, 100g:300mL, more preferably 100g:300mL.

[0023] The working principle and beneficial effects of the present invention are: In the present invention, nicotinamide can be prepared using 3-aminomethylpyridine as a raw material in the presence of a catalyst. The catalyst comprises potassium permanganate and a composite manganese oxide. The composite manganese oxide uses zirconium dioxide as a carrier, and a titanium source and a water-soluble manganese salt as active catalytic components. The adsorption of the titanium source and the water-soluble manganese salt by zirconium dioxide increases the catalytically active sites of the composite manganese oxide, thereby improving the catalytic efficiency of 3-aminomethylpyridine. In combination with potassium permanganate, the prepared nicotinamide has a high yield and purity. DETAILED DESCRIPTION

[0024] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making any creative efforts are within the scope of protection of the present invention.

[0025] Example 1 The preparation method of composite manganese oxide comprises the following steps: A1. Dissolve 3 g of manganese nitrate, 0.1 g of tetraisopropyl titanate, and 0.4 g of titanyl sulfate in 40 mL of water, and stir at 500 rpm for 20 min to obtain a mixed solution; A2. Add 20 g of zirconium dioxide to the mixture, stir at 300 rpm for 80 min, concentrate, dry, and calcine at 350° C. for 1.5 h to obtain a composite manganese oxide; A method for synthesizing high-purity nicotinamide comprises the following steps: S1. Mix 100 g of 3-aminomethylpyridine, 12 g of potassium permanganate, 8 g of complex manganese oxide, and 400 mL of ethanol, react at 45° C. for 8 h, filter, and cool to 0° C. to obtain crude nicotinamide; S2. Mix the crude nicotinamide with 200 mL of ethanol, cool the mixture to 15° C. at a cooling rate of 4° C. / min, and then cool the mixture to 5° C. at a cooling rate of 0.5° C. / min to obtain 109.78 g of nicotinamide. Among them, the yield of nicotinamide is 96.87% and the purity is 99.53%.

[0026] Example 2 The preparation method of composite manganese oxide comprises the following steps: A1. Dissolve 3 g of manganese nitrate, 0.1 g of tetraisopropyl titanate, and 0.4 g of titanyl sulfate in 40 mL of water, and stir at 600 rpm for 15 min to obtain a mixed solution. A2. Add 20 g of zirconium dioxide to the mixture, stir at a stirring speed of 350 rpm for 60 min, concentrate, dry, and calcine at 350° C. for 1.5 h to obtain a composite manganese oxide; A method for synthesizing high-purity nicotinamide comprises the following steps: S1. Mix 100 g of 3-aminomethylpyridine, 15 g of potassium permanganate, 10 g of complex manganese oxide, and 450 mL of ethanol, react at 50° C. for 7 h, filter, and cool to 0° C. to obtain crude nicotinamide; S2. Mix the crude nicotinamide and 300 mL of ethanol, cool the mixture to 12° C. at a cooling rate of 6° C. / min, and then cool the mixture to 3° C. at a cooling rate of 1° C. / min to obtain 110.22 g of nicotinamide; Among them, the yield of nicotinamide is 97.21% and the purity is 99.48%.

[0027] Example 3 The preparation method of composite manganese oxide comprises the following steps: A1. Dissolve 3 g of manganese nitrate, 0.1 g of tetraisopropyl titanate, and 0.4 g of titanyl sulfate in 40 mL of water, and stir at 700 rpm for 10 min to obtain a mixed solution. A2. Add 20 g of zirconium dioxide to the mixture, stir at 400 rpm for 50 min, concentrate, dry, and calcine at 400° C. for 1 h to obtain a composite manganese oxide; A method for synthesizing high-purity nicotinamide comprises the following steps: S1. Mix 100 g of 3-aminomethylpyridine, 15 g of potassium permanganate, 15 g of complex manganese oxide, and 550 mL of ethanol, react at 55° C. for 6 h, filter, and cool to 0° C. to obtain crude nicotinamide; S2. Mix the crude nicotinamide and 300 mL of ethanol, cool the mixture to 10°C at a cooling rate of 8°C / min, and then cool the mixture to 0°C at a cooling rate of 1.5°C / min to obtain 109.91 g of nicotinamide. Among them, the yield of nicotinamide is 97.02% and the purity is 99.56%.

[0028] Example 4 The only difference between this embodiment and embodiment 2 is that in the preparation method of the composite manganese oxide of this embodiment, the mass of manganese nitrate added is 4 g; 110.40 g of nicotinamide is obtained, the yield of nicotinamide is 97.44%, and the purity is 99.55%.

[0029] Example 5 The only difference between this embodiment and embodiment 2 is that in the preparation method of the composite manganese oxide of this embodiment, the mass of manganese nitrate added is 5 g; 110.58 g of nicotinamide is obtained, the yield of nicotinamide is 97.56%, and the purity is 99.51%.

[0030] Example 6 The only difference between this embodiment and embodiment 2 is that in the preparation method of the composite manganese oxide of this embodiment, the mass of manganese nitrate added is 7 g; 110.04 g of nicotinamide is obtained, the yield of nicotinamide is 97.15%, and the purity is 99.58%.

[0031] Example 7 The only difference between this embodiment and embodiment 5 is that step S2 of the method for synthesizing high-purity nicotinamide in this embodiment is different, specifically: S2. Mix the crude nicotinamide with 240 mL of ethanol and 60 mL of propylene glycol methyl ether acetate, cool the mixture to 12° C. at a cooling rate of 6° C. / min, and then cool the mixture to 3° C. at a cooling rate of 1° C. / min to obtain 110.44 g of nicotinamide. Among them, the yield of nicotinamide is 97.61% and the purity is 99.69%.

[0032] Example 8 The only difference between this embodiment and Example 7 is that in step S2 of this embodiment, 250 mL of ethanol and 50 mL of propylene glycol methyl ether acetate were added; 110.40 g of nicotinamide was obtained, with a yield of 97.64% and a purity of 99.75%.

[0033] Example 9 The only difference between this embodiment and Example 7 is that in step S2 of this embodiment, 270 mL of ethanol and 30 mL of propylene glycol methyl ether acetate were added; 110.39 g of nicotinamide was obtained, with a yield of 97.59% and a purity of 99.71%.

[0034] Example 10 The only difference between this embodiment and embodiment 9 is that step S2 of the method for synthesizing high-purity nicotinamide in this embodiment is different, specifically: S2. Mix the crude nicotinamide with 270 mL of ethanol and 30 mL of propylene glycol methyl ether acetate, and cool the mixture to 0°C at a cooling rate of 6°C / min to obtain 110.39 g of nicotinamide. Among them, the yield of nicotinamide is 97.45% and the purity is 99.57%.

[0035] Comparative Example 1 The only difference between this comparative example and Example 2 is that in this comparative example, the composite manganese oxide is replaced by an equal amount of manganese dioxide; 98.24 g of nicotinamide is obtained, the yield of nicotinamide is 85.92%, and the purity is 98.65%.

[0036] Comparative Example 2 The only difference between this comparative example and Example 2 is that in this comparative example, the composite manganese oxide is replaced by an equal amount of titanium dioxide; 73.84 g of nicotinamide is obtained, the yield of nicotinamide is 64.18%, and the purity is 98.04%.

[0037] Comparative Example 3 The only difference between this comparative example and Example 2 is that in this comparative example, 10 g of the composite manganese oxide is replaced with 5 g of manganese dioxide and 5 g of titanium dioxide; 100.28 g of nicotinamide is obtained, the yield of nicotinamide is 88.16%, and the purity is 99.16%.

[0038] Comparative Example 4 The only difference between this comparative example and Example 2 is that in this comparative example, no composite manganese oxide is added; 55.90 g of nicotinamide is obtained, the yield of nicotinamide is 97.57%, and the purity is 97.57%.

[0039] Comparative Example 5 The only difference between this comparative example and Example 2 is that potassium permanganate was not added in this comparative example; 77.12 g of nicotinamide was obtained, the yield of nicotinamide was 67.27%, and the purity was 98.39%.

[0040] Compared with Comparative Examples 1 to 5, the yield and purity of nicotinamide synthesized in Examples 1 to 6 were improved, with the yield reaching 96.87% and the purity reaching 99.53%. This indicates that when a composite manganese oxide formed by a water-soluble manganese salt, a titanium source, and zirconium dioxide is used as a catalyst in combination with potassium permanganate, nicotinamide with a higher yield and purity can be prepared.

[0041] Compared with Example 5, the purity of Examples 7 to 9 is improved, indicating that when the second solvent further includes propylene glycol methyl ether acetate, the purity of nicotinamide can be further improved by crystallizing the crude nicotinamide with ethanol and propylene glycol methyl ether acetate, and the purity can reach more than 99.69%.

[0042] The above are only preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A method for synthesizing high-purity nicotinamide, characterized in that: The following steps are involved: S1. Evenly mix 3-aminomethylpyridine, a catalyst, and a first solvent, react, filter, and cool to obtain a crude nicotinamide; S2. mixing the crude nicotinamide and a second solvent, cooling and crystallizing, to obtain the high-purity nicotinamide; The catalyst comprises potassium permanganate and composite manganese oxide in a weight ratio of 1.5:1 to 1.5; The raw materials of the composite manganese oxide include water-soluble manganese salt, titanium source and zirconium dioxide; The first solvent includes ethanol; The second solvent includes ethanol.

2. The method for synthesizing high-purity nicotinamide according to claim 1, wherein: The water-soluble manganese salt includes one or more of manganese nitrate, manganese sulfate and manganese chloride.

3. The method for synthesizing high-purity nicotinamide according to claim 1, characterized in that: The titanium source includes one or both of an organic titanium source and an inorganic titanium source; The organic titanium source includes one or both of tetraisopropyl titanate and tetraethyl titanate; The inorganic titanium source includes one or both of titanyl sulfate and titanium sulfate.

4. The method for synthesizing high-purity nicotinamide according to claim 1, wherein: The weight ratio of the zirconium dioxide, the titanium source, and the water-soluble manganese salt is 20:0.5:3-7.

5. The method for synthesizing high-purity nicotinamide according to claim 1, wherein: The preparation method of the composite manganese oxide comprises the following steps: A1, dissolving the water-soluble manganese salt and titanium source in water and dispersing them uniformly to obtain a mixed solution; A2. Add the zirconium dioxide to the mixed solution, disperse it evenly, concentrate it, dry it, and calcine it to obtain a composite manganese oxide.

6. The method for synthesizing high-purity nicotinamide according to claim 1, characterized in that: The second solvent also includes propylene glycol methyl ether acetate; In the second solvent, the weight ratio of ethanol to propylene glycol methyl ether acetate is 4-9:

1.

7. The method for synthesizing high-purity nicotinamide according to claim 1, characterized in that: The cooling crystallization is divided into a first stage cooling crystallization and a second stage cooling crystallization; During the first stage of cooling crystallization, the temperature is cooled to 10-15°C at a cooling rate of 4-8°C / min; During the second stage of cooling crystallization, the temperature is cooled to 0-5°C at a cooling rate of 0.5-1.5°C / min.

8. The method for synthesizing high-purity nicotinamide according to claim 1, characterized in that: The amount of the catalyst is 20% to 30% of the mass of the 3-aminomethylpyridine; In terms of g / mL, the mass volume ratio of the 3-aminomethylpyridine to the first solvent is 100 g:400-550 mL.

9. The method for synthesizing high-purity nicotinamide according to claim 1, characterized in that: In step S1, the reaction temperature is 45-55° C. and the reaction time is 6-8 hours.

10. The method for synthesizing high-purity nicotinamide according to claim 1, characterized in that: In terms of g / mL, the mass volume ratio of the 3-aminomethylpyridine to the second solvent is 100 g:200-300 mL.