A method for synthesizing nicotinamide

Abstract

This invention discloses a method for synthesizing nicotinamide, relating to the field of fine chemical and pharmaceutical intermediate synthesis technology. It employs a two-step tandem reaction process: The first step uses 3-methylpyridine as a starting material, and catalytically oxidizes it to nicotinic acid in an oxygen atmosphere with a purity ≥99.5% under the action of a composite catalyst composed of N-hydroxyphthalimide and cobalt acetylacetonate; the second step uses the obtained nicotinic acid as a raw material, and reacts it with ammonium chloride in the action of EDC (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride) activator to synthesize nicotinamide. The process of this invention features mild reaction conditions, a total yield of 77.7-78.2% for both steps, a product purity ≥99.5%, a solvent recovery rate ≥85%, and is simple to operate, highly stable, and suitable for industrial mass production and small-scale laboratory synthesis.

Description

Technical Field

[0001] This invention relates to the field of fine chemical and pharmaceutical intermediate synthesis technology, and in particular to a method for synthesizing nicotinamide. Background Technology

[0002] To address nicotinamide (also known as niacinamide), an amide derivative of nicotinic acid, it is a white crystalline powder, odorless or with a slightly off-taste, slightly bitter, and slightly hygroscopic. It has excellent solubility, readily soluble in water and ethanol, and stably soluble in glycerol.

[0003] In the field of application, nicotinamide has a wide range of uses: clinically, it is a core drug for the prevention and treatment of pellagra, stomatitis, and glossitis, and also has an adjunctive therapeutic effect on cardiovascular-related diseases such as sick sinus syndrome and atrioventricular block; in the cosmetics field, it has become a popular active ingredient due to its effects of repairing the skin barrier, brightening skin tone, and moisturizing and locking in moisture; in addition, it can also be used as a feed additive and food fortifier, and the market demand remains stable.

[0004] Existing methods for synthesizing nicotinamide suffer from problems such as harsh reaction conditions, difficulty in solvent recovery, numerous byproducts, or unstable yields, which limit the economic and environmental benefits of its industrial application.

[0005] Therefore, developing a synthesis process that is high-yield, easy to operate, mild, and environmentally friendly is of great practical significance. Summary of the Invention

[0006] To address the aforementioned problems, this application proposes a method for synthesizing nicotinamide, aiming to solve the issues of harsh reaction conditions, difficult solvent recovery, numerous byproducts, and unstable yields in existing nicotinamide synthesis processes. The specific steps are as follows: A method for synthesizing nicotinamide, comprising the following steps: S1. Preparation of nicotinic acid: 3-Methylpyridine was added to acetic acid solvent and catalytically oxidized in an oxygen atmosphere with a purity of ≥99.5% under the action of a composite catalyst system composed of N-hydroxyphthalimide and cobalt acetylacetonate. After the reaction was completed, nicotinic acid was obtained through post-processing. S2, formation of nicotinamide: Nicotinic acid obtained from S1 was added to DMSO solvent, and activator 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) was added. After activation by stirring at room temperature, the temperature was raised to react with ammonium chloride to undergo an amidation reaction. After the reaction was completed, the pH of the system was adjusted to 5.8-6.2 with a 10% citric acid solution, and the nicotinamide product was obtained after post-processing.

[0007] Specifically, the reaction temperature for the catalytic oxidation reaction in S1 is 85-95℃, and the reaction time is 6.5-7.5h. The activation time for S2 with room temperature stirring is 35-45 min; The temperature reached by heating is 85-95℃; The amidation reaction takes 4.5-5.5 hours.

[0008] Specifically, the amounts of each raw material and reagent in S1 are as follows: The amount of N-hydroxyphthalimide used relative to 1 mol of 3-methylpyridine is 0.15-0.25 mol, the amount of cobalt acetylacetonate is 0.35-0.45% mol, and the amount of acetic acid is 650-750 mL.

[0009] Preferably, the preferred amounts of each raw material and reagent in S1 are: The amount of N-hydroxyphthalimide, N-acetylacetonate cobalt, and acetic acid is 0.2 mol relative to 1 mol of 3-methylpyridine. The preferred reaction temperature is 90℃ and the preferred reaction time is 7 h.

[0010] Specifically, the post-processing described in S1 includes: After the reaction was completed, acetic acid was recovered by vacuum distillation under a vacuum of 0.08-0.09 MPa. Add a mixture of ethyl acetate and deionized water in a volume ratio of 1:1 to the distillation residue, stir for 15-20 min, and then let it stand to separate into layers. The lower aqueous phase was collected and extracted three times with ethyl acetate, each time using half the volume of the aqueous phase. The organic phases were then combined. The organic phase was concentrated to dryness under reduced pressure at a temperature of 45-55℃ and a vacuum degree of 0.09-0.095MPa to obtain crude nicotinic acid. The crude product was recrystallized with diethyl ether, the amount of diethyl ether being 8-10 times the mass of the crude product. After filtration, it was vacuum dried at 40°C for 3 hours to obtain nicotinic acid product.

[0011] Specifically, the amounts of each raw material and reagent used in S2 are as follows: Compared to 0.5 mol nicotinic acid, the amount of DMSO used is 300-400 mL, and the amount of EDC used is 0.6-0.9 mol.

[0012] Preferably, the preferred amounts of each raw material and reagent in S2 are: The amount of DMSO used is 350 mL relative to 0.5 mol nicotinic acid, and the amount of EDC used is 0.75 mol; the preferred stirring and activation time before the reaction is 40 min, the preferred reaction temperature is 90℃, the preferred reaction time is 5 h, and the preferred pH value of the system is 6.0.

[0013] Specifically, the post-processing described in S2 includes: After adjusting the pH value, allow the mixture to stand and separate into layers. Take the lower aqueous phase and extract it three times with dichloromethane, using 60-90 mL of extractant each time. Combine the organic phases. Add anhydrous magnesium sulfate to the organic phase and dry for 2 hours, then filter to remove the desiccant; The filtrate was concentrated to dryness under reduced pressure at a temperature of 40-50℃ and a vacuum degree of 0.09-0.095MPa to obtain crude nicotinamide. The crude product was recrystallized with diethyl ether, the amount of diethyl ether being 2-2.8 times the volume of the crude product. After filtration, it was vacuum dried at 35°C for 2.5 hours to obtain the nicotinamide product.

[0014] Specifically, the yield of nicotinic acid obtained from S1 is 80-81%, and the purity is ≥99.2%. The yield of nicotinamide obtained by S2 was 96.5-97.5%, with a purity ≥99.5%, and the overall yield of the two-step reaction was 77.7-78.2%.

[0015] Specifically, the acetic acid recovered in S1 can be recycled after dehydration, and the dichloromethane used for extraction in S2 can be recycled after distillation, with a solvent recovery rate of ≥85%.

[0016] In summary, the method for synthesizing nicotinamide according to the present invention has the following advantages compared with traditional techniques: 1. The overall yield of the two-step reaction in this application can reach 77.7-78.2%, and the purity of the finished product is ≥99.5%. Compared with the traditional process, the yield is increased by 3-5 percentage points, and the purity meets the requirements of pharmaceutical and cosmetic applications. 2. The reaction conditions in this application are mild (temperature 85-95℃, pressure close to atmospheric pressure), avoiding equipment damage and safety risks caused by high temperature and high pressure; the catalyst dosage is optimized, reducing production costs; 3. The solvents in this application, such as acetic acid and dichloromethane, can be recovered and recycled through distillation and rectification, with a recovery rate of ≥85%, reducing solvent waste and environmental pollution; 4. The process steps in this application are clear, and the post-processing only involves routine operations such as extraction, concentration, and recrystallization. No complex equipment is required, making it suitable for large-scale production and laboratory preparation. 5. The optimized parameter range of this application has wide applicability, the reaction process is easy to control, the product quality fluctuates little, and the industrial reproducibility is good.

[0017] The technical method of the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Attached Figure Description

[0018] Figure 1 This is a schematic diagram illustrating the steps of a method for synthesizing nicotinamide. Detailed Implementation

[0019] The technical method of the present invention will be further described below with reference to the accompanying drawings and embodiments. It should be noted that, unless otherwise specifically stated, the relative arrangement, numerical expressions, and values ​​of the components and steps described in these embodiments do not limit the scope of this application.

[0020] The following description of at least one exemplary embodiment is merely illustrative and is in no way intended to limit the scope of this application and its application or use.

[0021] Techniques, systems, and equipment known to those skilled in the art may not be discussed in detail, but where appropriate, they should be considered part of the instruction manual.

[0022] In all the examples shown and discussed herein, any specific values ​​should be interpreted as merely exemplary and not as limitations. Therefore, other examples of exemplary embodiments may have different values.

[0023] Unless otherwise defined, the technical or scientific terms used in this invention shall have the ordinary meaning as understood by one of ordinary skill in the art to which this invention pertains.

[0024] An optimized and environmentally friendly method for preparing nicotinamide is proposed, suitable for industrial-scale production and small-scale laboratory synthesis. Figure 1 As shown, it includes: S1. Preparation of nicotinic acid: 3-Methylpyridine was added to acetic acid solvent and catalytically oxidized in an oxygen atmosphere with a purity of ≥99.5% under the action of a composite catalyst system composed of N-hydroxyphthalimide and cobalt acetylacetonate. After the reaction was completed, nicotinic acid was obtained through post-processing. S2, formation of nicotinamide: Nicotinic acid obtained from S1 was added to DMSO solvent, and activator 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) was added. After activation by stirring at room temperature, the temperature was raised to react with ammonium chloride to undergo an amidation reaction. After the reaction was completed, the pH of the system was adjusted to 5.8-6.2 with a 10% citric acid solution, and the nicotinamide product was obtained after post-processing.

[0025] Example 1 Add 1 mol of 3-methylpyridine, 0.2 mol of N-hydroxyphthalimide, 0.4% mol of cobalt acetylacetonate (relative to 3-methylpyridine) and 700 mL of acetic acid to a 5 L high-pressure reactor. After sealing the reactor, purge the air inside the reactor with oxygen of ≥99.5% purity three times, maintain the oxygen pressure at 0.1 MPa, raise the temperature to 90 °C, and stir the reaction for 7 h.

[0026] After the reaction was completed, acetic acid was recovered by vacuum distillation under a vacuum of 0.08-0.09 MPa. 1 L of ethyl acetate and 1 L of deionized water were added to the distillation residue, and the mixture was stirred for 20 min and then allowed to stand for separation. The aqueous phase was extracted three times with 500 mL of ethyl acetate each time, and the organic phases were combined. The organic phase was concentrated to dryness under vacuum at 45-55℃ and a vacuum of 0.09-0.095 MPa to obtain crude nicotinic acid. The crude product was recrystallized from the crude product using diethyl ether, with the amount of diethyl ether being 8-10 times the weight of the crude product. After filtration, the product was dried under vacuum at 40℃ for 3 h to obtain the nicotinic acid product. The yield of nicotinic acid obtained in this step was 80.5%, and the purity was 99.3%.

[0027] Add 0.5 mol of the prepared nicotinic acid and 350 mL of DMSO to a 2 L three-necked flask, stir until completely dissolved, then add 0.75 mol of EDC and stir at room temperature for 40 min to activate. Raise the temperature to 90 °C and react at a constant temperature for 5 h, taking samples every 1 h to monitor the reaction progress.

[0028] After the reaction was completed, the reaction solution was cooled to room temperature, and 10% citric acid solution was slowly added to adjust the pH of the system to 6.0. After standing and separating the layers, the lower aqueous phase was taken out and extracted three times with dichloromethane, 75 mL each time. The organic phases were combined. Anhydrous magnesium sulfate was added to the organic phase and dried for 2 h. The desiccant was removed by filtration. The filtrate was concentrated to dryness under reduced pressure at 40-50℃ and 0.09-0.095 MPa to obtain crude nicotinamide. The crude product was recrystallized with 2.5 times the volume of diethyl ether, filtered, and dried under vacuum at 35℃ for 2.5 h to obtain the finished nicotinamide product.

[0029] The nicotinamide prepared in this example had a yield of 97.2% and a purity of 99.6%, with a total yield of approximately 78.3% for both steps.

[0030] Example 2 Add 1 mol of 3-methylpyridine, 0.18 mol of N-hydroxyphthalimide, 0.38% mol of cobalt acetylacetonate (relative to 3-methylpyridine) and 680 mL of acetic acid to a 5 L high-pressure reactor. After sealing the reactor, purge the air inside the reactor with oxygen of ≥99.5% purity three times, maintain the oxygen pressure at 0.1 MPa, raise the temperature to 88 °C, and stir the reaction for 7.2 h.

[0031] After the reaction was completed, acetic acid was recovered by vacuum distillation under a vacuum of 0.08-0.09 MPa. 1 L of ethyl acetate and 1 L of deionized water were added to the distillation residue, and the mixture was stirred for 20 min and then allowed to stand for separation. The aqueous phase was extracted three times with 500 mL of ethyl acetate each time, and the organic phases were combined. The organic phase was concentrated to dryness under vacuum at 45-55℃ and a vacuum of 0.09-0.095 MPa to obtain crude nicotinic acid. The crude product was recrystallized from the crude product using diethyl ether, with the amount of ether being 8-10 times the weight of the crude product. After filtration, the product was dried under vacuum at 40℃ for 3 h to obtain the nicotinic acid product. The yield of nicotinic acid obtained in this step was 80.2%, and the purity was 99.2%.

[0032] Add 0.5 mol of the prepared nicotinic acid and 350 mL of DMSO to a 2 L three-necked flask, stir until completely dissolved, then add 0.7 mol of EDC and stir at room temperature for 38 min to activate. Raise the temperature to 88 °C and keep the reaction at a constant temperature for 5.2 h, taking samples every 1 h to monitor the reaction progress.

[0033] After the reaction was completed, the reaction solution was cooled to room temperature, and 10% citric acid solution was slowly added to adjust the pH of the system to 6.0. After standing and separating the layers, the lower aqueous phase was taken out and extracted three times with dichloromethane, 70 mL each time. The organic phases were combined. Anhydrous magnesium sulfate was added to the organic phase and dried for 2 h. The desiccant was removed by filtration. The filtrate was concentrated to dryness under reduced pressure at 40-50℃ and 0.09-0.095 MPa to obtain crude nicotinamide. The crude product was recrystallized with 2.5 times the volume of diethyl ether, filtered, and dried under vacuum at 35℃ for 2.5 h to obtain the finished nicotinamide product.

[0034] The nicotinamide prepared in this example had a yield of 96.8% and a purity of 99.5%, with a total yield of approximately 77.6% for both steps.

[0035] Example 3 Add 1 mol of 3-methylpyridine, 0.15 mol of N-hydroxyphthalimide, 0.35% mol of cobalt acetylacetonate (relative to 3-methylpyridine) and 650 mL of acetic acid to a 5 L high-pressure reactor. After sealing the reactor, purge the air inside the reactor with oxygen of ≥99.5% purity three times, maintain the oxygen pressure at 0.1 MPa, raise the temperature to 85 °C, and stir the reaction for 6.5 h.

[0036] After the reaction was completed, acetic acid was recovered by vacuum distillation under a vacuum of 0.08-0.09 MPa. 1 L of ethyl acetate and 1 L of deionized water were added to the distillation residue, and the mixture was stirred for 15 min and then allowed to stand for separation. The aqueous phase was extracted three times with 500 mL of ethyl acetate each time, and the organic phases were combined. The organic phase was concentrated to dryness under vacuum at 45 °C and 0.09 MPa to obtain crude nicotinic acid. The crude product was recrystallized from the crude product using diethyl ether, with the amount of ether being 8 times the weight of the crude product. After filtration, the product was dried under vacuum at 40 °C for 3 h to obtain the nicotinic acid product. The yield of nicotinic acid obtained in this step was 79.8%, and the purity was 99.2%.

[0037] Add 0.5 mol of the prepared nicotinic acid and 300 mL of DMSO to a 2 L three-necked flask, stir until completely dissolved, then add 0.6 mol of EDC and stir at room temperature for 35 min to activate. Raise the temperature to 85 °C and react at a constant temperature for 4.5 h, taking samples every 1 h to monitor the reaction progress.

[0038] After the reaction was completed, the reaction solution was cooled to room temperature, and a 10% (w / w) citric acid solution was slowly added to adjust the pH of the system to 5.8. After standing and separating the layers, the lower aqueous phase was collected and extracted three times with dichloromethane, 60 mL each time. The organic phases were combined. Anhydrous magnesium sulfate was added to the organic phase and dried for 2 hours. The desiccant was removed by filtration. The filtrate was concentrated to dryness under reduced pressure at 40°C and 0.09 MPa to obtain crude nicotinamide. The crude product was recrystallized with twice the volume of diethyl ether, filtered, and then dried under vacuum at 35°C for 2.5 hours to obtain the finished nicotinamide product. The yield of nicotinamide obtained in this example was 96.5%, the purity was 99.5%, and the overall yield of the two steps was approximately 77.0%.

[0039] Example 4 Add 1 mol of 3-methylpyridine, 0.25 mol of N-hydroxyphthalimide, 0.45% mol of cobalt acetylacetonate (relative to 3-methylpyridine) and 750 mL of acetic acid to a 5 L high-pressure reactor. After sealing the reactor, purge the air inside the reactor with oxygen of ≥99.5% purity three times, maintain the oxygen pressure at 0.1 MPa, raise the temperature to 95 °C, and stir the reaction for 7.5 h.

[0040] After the reaction was completed, acetic acid was recovered by vacuum distillation under a vacuum of 0.08-0.09 MPa. 1 L of ethyl acetate and 1 L of deionized water were added to the distillation residue, and the mixture was stirred for 20 min and then allowed to stand for separation. The aqueous phase was extracted three times with 500 mL of ethyl acetate each time, and the organic phases were combined. The organic phase was concentrated to dryness under vacuum at 55 °C and 0.095 MPa to obtain crude nicotinic acid. The crude product was recrystallized from the crude product using diethyl ether, with the amount of ether being 10 times the weight of the crude product. After filtration, the product was dried under vacuum at 40 °C for 3 h to obtain the nicotinic acid product. The yield of nicotinic acid obtained in this step was 81.0%, and the purity was 99.4%.

[0041] Add 0.5 mol of the prepared nicotinic acid and 400 mL of DMSO to a 2 L three-necked flask, stir until completely dissolved, then add 0.9 mol of EDC and stir at room temperature for 45 min to activate. Raise the temperature to 95 °C and keep the reaction at a constant temperature for 5.5 h, taking samples every 1 h to monitor the reaction progress.

[0042] After the reaction was completed, the reaction solution was cooled to room temperature, and a 10% (w / w) citric acid solution was slowly added to adjust the pH of the system to 6.2. After standing and separating the layers, the lower aqueous phase was collected and extracted three times with dichloromethane, 90 mL each time. The organic phases were combined. Anhydrous magnesium sulfate was added to the organic phase and dried for 2 hours. The desiccant was removed by filtration. The filtrate was concentrated to dryness under reduced pressure at 50°C and 0.095 MPa to obtain crude nicotinamide. The crude product was recrystallized from the crude product with 2.8 times its volume of diethyl ether, filtered, and then dried under vacuum at 35°C for 2.5 hours to obtain the finished nicotinamide product. The yield of nicotinamide obtained in this example was 97.5%, the purity was 99.6%, and the overall yield of the two steps was approximately 79.0%.

[0043] Within the full range of parameters defined in the claims of this invention, the yield of nicotinic acid is consistently between 79.8% and 81.0%, the yield of nicotinamide is consistently between 96.5% and 97.5%, and the purity of the products is ≥99.2%, demonstrating that the process of this invention has an extremely wide operating window and excellent industrial reproducibility.

[0044] Comparative Example 1 Traditional high-temperature ammonolysis of nicotinic acid.

[0045] Add 0.5 mol nicotinic acid, 200 mL of 25% ammonia water and 0.05 mol zinc oxide catalyst to a 2L high-pressure reactor. After sealing the reactor, raise the temperature to 180℃, maintain the pressure inside the reactor at 2.0 MPa, and stir the reaction for 8 hours.

[0046] After the reaction was completed, the mixture was cooled to room temperature, the pressure inside the reactor was slowly released, and the reaction solution was transferred to a beaker. Excess ammonia was removed by vacuum distillation, and the mixture was concentrated to 1 / 3 of its original volume. After cooling and crystallization, the crude nicotinamide was obtained by filtration. The crude product was recrystallized with anhydrous ethanol, filtered, and then dried under vacuum at 60°C for 4 hours to obtain the finished nicotinamide product. The yield of nicotinamide obtained in this comparative example was 82.3%, and the purity was 98.5%.

[0047] Comparative Example 2 3-Methylpyridine direct ammonia oxidation method.

[0048] 1 mol of 3-methylpyridine was mixed with 3 mol of ammonia and 10 mol of air, preheated to 300°C, and then introduced into a fluidized bed reactor containing vanadium-titanium oxide catalyst. The reaction temperature was controlled at 380°C and the contact time was 2 seconds.

[0049] The reactant gas was absorbed by water, acidified with hydrochloric acid to pH=2, and cooled to crystallize, yielding crude nicotinic acid. The crude nicotinic acid was dissolved in hot water, decolorized with activated carbon, filtered, and cooled to crystallize, yielding refined nicotinic acid. The refined nicotinic acid was mixed with urea at a molar ratio of 1:1.2 and reacted at 220℃ for 3 hours. After cooling, it was dissolved in hot water, decolorized with activated carbon, cooled to crystallize, filtered, and dried to obtain the final nicotinamide product. The total yield of nicotinamide obtained in this comparative example was 68.5%, with a purity of 98.8%.

[0050] Results analysis: Table 1 shows a comparative analysis of the effects of the examples and comparative examples: Table 1 Comparison of the effects of the examples and comparative examples.

[0051] Compared with the prior art, the present invention has the following significant advantages: The reaction conditions are extremely mild, avoiding equipment damage and safety risks caused by high temperature and high pressure; The product has higher purity (≥99.5%), which can directly meet the requirements of pharmaceutical and cosmetic applications; High solvent recovery rate significantly reduces production costs and environmental pollution; The process is simple, requires no special equipment, and is easy to scale up for industrial production.

[0052] Finally, it should be noted that the above embodiments are only used to illustrate the technical methods of the present invention and not to limit them. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can still be made to the technical methods of the present invention, and these modifications or equivalent substitutions cannot cause the modified technical methods to deviate from the spirit and scope of the technical methods of the present invention.

Claims

1. A method for synthesizing nicotinamide, characterized in that, Includes the following steps: S1. Preparation of nicotinic acid: 3-Methylpyridine was added to acetic acid solvent and catalytically oxidized in an oxygen atmosphere with a purity of ≥99.5% under the action of a composite catalyst system composed of N-hydroxyphthalimide and cobalt acetylacetonate. After the reaction was completed, nicotinic acid was obtained through post-processing. S2, formation of nicotinamide: Nicotinic acid obtained from S1 was added to DMSO solvent, and activator 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride EDC was added. After activation by stirring at room temperature, the temperature was raised to react with ammonium chloride to undergo an amidation reaction. After the reaction was completed, the pH of the system was adjusted to 5.8-6.2 with a 10% citric acid solution, and the nicotinamide product was obtained after post-processing.

2. The method for synthesizing nicotinamide according to claim 1, characterized in that, The reaction temperature for the catalytic oxidation reaction in S1 is 85-95℃, and the reaction time is 6.5-7.5h. The activation time for S2 with room temperature stirring is 35-45 min; The temperature reached by heating is 85-95℃; The amidation reaction takes 4.5-5.5 hours.

3. The method for synthesizing nicotinamide according to claim 1, characterized in that, The amounts of each raw material and reagent in S1 are as follows: The amount of N-hydroxyphthalimide used relative to 1 mol of 3-methylpyridine is 0.15-0.25 mol, the amount of cobalt acetylacetonate is 0.35-0.45% mol, and the amount of acetic acid is 650-750 mL.

4. The method for synthesizing nicotinamide according to claim 3, characterized in that, The amounts of each raw material and reagent in S1 are as follows: The amount of N-hydroxyphthalimide used relative to 1 mol of 3-methylpyridine was 0.2 mol, the amount of cobalt acetylacetonate was 0.4% mol, and the amount of acetic acid was 700 mL; the reaction temperature was 90℃, and the reaction time was 7 h.

5. The method for synthesizing nicotinamide according to claim 1, characterized in that, The post-processing described in S1 specifically includes: After the reaction was completed, acetic acid was recovered by vacuum distillation under a vacuum of 0.08-0.09 MPa. Add a mixture of ethyl acetate and deionized water in a volume ratio of 1:1 to the distillation residue, stir for 15-20 min, and then let it stand to separate into layers. The lower aqueous phase was collected and extracted three times with ethyl acetate, each time using half the volume of the aqueous phase. The organic phases were then combined. The organic phase was concentrated to dryness under reduced pressure at a temperature of 45-55℃ and a vacuum degree of 0.09-0.095MPa to obtain crude nicotinic acid. The crude product was recrystallized with diethyl ether, the amount of diethyl ether being 8-10 times the mass of the crude product. After filtration, it was vacuum dried at 40°C for 3 hours to obtain nicotinic acid product.

6. The method for synthesizing nicotinamide according to claim 1, characterized in that, The amounts of each raw material and reagent used in S2 are as follows: Compared to 0.5 mol nicotinic acid, the amount of DMSO used is 300-400 mL, and the amount of EDC used is 0.6-0.9 mol.

7. The method for synthesizing nicotinamide according to claim 6, characterized in that, The amounts of each raw material and reagent used in S2 are as follows: The amount of DMSO used is 350 mL, and the amount of EDC used is 0.75 mol, relative to 0.5 mol nicotinic acid. The pre-reaction stirring activation time was 40 min, the reaction temperature was 90℃, the reaction time was 5 h, and the pH of the system was adjusted to 6.

0.

8. The method for synthesizing nicotinamide according to claim 1, characterized in that, The post-processing described in S2 specifically includes: After adjusting the pH value, allow the mixture to stand and separate into layers. Take the lower aqueous phase and extract it three times with dichloromethane, using 60-90 mL of extractant each time. Combine the organic phases. Add anhydrous magnesium sulfate to the organic phase and dry for 2 hours, then filter to remove the desiccant; The filtrate was concentrated to dryness under reduced pressure at a temperature of 40-50℃ and a vacuum degree of 0.09-0.095MPa to obtain crude nicotinamide. The crude product was recrystallized with diethyl ether, the amount of diethyl ether being 2-2.8 times the volume of the crude product. After filtration, it was vacuum dried at 35°C for 2.5 hours to obtain the nicotinamide product.

9. The method for synthesizing nicotinamide according to claim 8, characterized in that, The yield of nicotinic acid obtained from S1 is 80-81%, and the purity is ≥99.2%. The yield of nicotinamide obtained by S2 was 96.5-97.5%, with a purity ≥99.5%, and the overall yield of the two-step reaction was 77.7-78.2%.

10. The method for synthesizing nicotinamide according to claim 9, characterized in that, The acetic acid recovered in S1 can be recycled after dehydration, and the dichloromethane used for extraction in S2 can be recycled after distillation. The solvent recovery rate is ≥85%.

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