Nicotinamide synthesis process based on catalytic oxidation system and application

Abstract

The application discloses a nicotinamide green synthesis process based on a double-activity-site composite molecular sieve catalytic oxidation system and products and applications thereof. The process uses 3-methylpyridine as raw material, and in a water-phase catalytic oxidation system formed by a core-shell double-activity-site composite molecular sieve catalyst and a green oxidant, nicotinic acid intermediates are selectively oxidized at normal pressure under 40-80 DEG C, then an ammonia source is added in the same system, and in-situ amidation is completed under the conditions of 60-100 DEG C and 0.1-0.5 MPa, so that nicotinamide is directly obtained by one-pot method without separation of the intermediates; the catalyst is separated and recovered, and low-temperature gradient crystallization is used for refining, so that high-purity nicotinamide products with a purity of greater than or equal to 99.5% and heavy metals less than 1 ppm are prepared. Compared with a traditional nitric acid oxidation-stepwise amination process, the three-waste emissions are reduced by more than 70%, the comprehensive production cost is reduced by more than 20%, and the process is suitable for continuous and intermittent industrial production.

Description

Technical Field

[0001] This invention relates to the field of fine chemical synthesis technology, specifically to a process for the green synthesis of nicotinamide using a multi-type dual-active-site core-shell composite molecular sieve catalytic oxidation system and 3-methylpyridine as raw material via a one-pot catalytic oxidation-in-situ ammoniation tandem reaction, as well as the high-purity nicotinamide product prepared by this process and the application of this process system in the industrial production of nicotinamide. Background Technology

[0002] Nicotinamide (CAS: 98-92-0), also known as vitamin B3 or nicotinamide, with the molecular formula C6H6N2O and a molecular weight of 122.12, is an important fine chemical product widely used in pharmaceutical intermediates, food additives, cosmetic active ingredients, and feed additives. Global annual demand for nicotinamide exceeds 30,000 tons, with China being the largest producer, accounting for over 60% of global production. With the rapid growth in demand for pharmaceutical-grade and cosmetic-grade nicotinamide, increasingly stringent requirements are being placed on product purity (≥99.5%), heavy metal residue (<1ppm), and green production practices.

[0003] Currently, the main industrial synthesis processes for nicotinamide include the following three categories: (1) Traditional nitric acid oxidation-stepwise ammoniation method: 3-methylpyridine is used as raw material, and concentrated nitric acid is used as oxidant. Gas-phase catalytic oxidation is carried out under high temperature of 220-260℃ and high pressure of 2-4MPa to obtain nicotinic acid. After separation and purification, nicotinic acid is then subjected to amidation reaction with liquid ammonia under high temperature and high pressure to obtain nicotinamide stepwise. This process has the following main defects: ① The oxidation step requires the use of concentrated nitric acid, which produces a large amount of nitrogen oxides (NOx) as byproducts. x ① The exhaust gas is severely polluting and requires a tail gas absorption system; ② The high-temperature and high-pressure reaction causes severe corrosion to the equipment, resulting in high maintenance costs; ③ The process is carried out in steps, and the intermediate nicotinic acid requires a complete separation and purification process, which is long and energy-intensive; ④ The overall yield is relatively low, usually between 65% and 75%; ⑤ The emissions of waste gas, wastewater, and solid waste are large, with each ton of nicotinamide generating approximately 50 to 80 tons of wastewater and approximately 0.8 to 1.2 tons of solid waste.

[0004] (2) Monofunctional catalyst catalytic oxidation method: Using metal oxide catalysts such as V2O5 and MoO3, with air or oxygen as the oxidant, 3-methylpyridine is catalytically oxidized in a gas-solid phase to prepare nicotinic acid, which is then aminated separately. Although this method reduces the amount of strong acid used to some extent, the catalyst only has a single oxidation function and no amination function, so it cannot realize the one-pot coupled reaction of oxidation and amination; the catalyst selectivity is not high, there are many by-products, and the catalyst life is limited, requiring frequent regeneration.

[0005] (3) Niacinyl hydration method: Nicotinamide is prepared by hydrolysis of 3-cyanopyridine (nicotinamide) under the catalysis of nitrile hydratase or acid-base catalysis. The raw material route of this method is different from that of the nitric acid oxidation method, but it also has the same problems as the high cost of raw materials, the high cost of nitrile hydratase production, the limited substrate concentration, and the difficulty of large-scale production.

[0006] Based on existing technologies, the following are the main technical shortcomings: (1) The lack of a bifunctional catalyst system that can simultaneously catalyze both oxidation and amination reactions means that the process cannot be completed in series in the same reaction system, and the separation of intermediates is inevitable. (2) Existing catalytic processes are generally limited to combinations of single catalysts and single oxidants, resulting in a narrow protection range and poor process adaptability; (3) Traditional oxidants (nitric acid, O2, etc.) have problems such as high pollution and many safety hazards, and there is a lack of green oxidant matching schemes suitable for mild aqueous systems; (4) The catalyst has poor stability, few cycles, is difficult to regenerate, and has high operating costs; (5) The multi-step process has high energy consumption and large emissions of waste gas, wastewater, and solid waste, which does not conform to the current development direction of green chemical industry.

[0007] In view of this, the present invention provides a one-pot green synthesis process based on multi-type dual-active-site composite molecular sieve catalytic oxidation-in-situ ammoniation, which fundamentally overcomes the above-mentioned technical defects. Summary of the Invention

[0008] The purpose of this invention is to provide a green synthesis process for nicotinamide based on a dual-active-site composite molecular sieve catalytic oxidation system. This process overcomes the shortcomings of existing technologies, such as stepwise operation, the necessity of intermediate separation, single catalyst function, high oxidant pollution, low product selectivity, and poor catalyst cycle stability. It achieves green, low-carbon, short-process, high-yield, and recyclable catalyst for the industrial production of high-purity nicotinamide. The invention also provides high-purity nicotinamide products prepared by this process, as well as the application of this catalytic oxidation system in the continuous or intermittent industrial production of nicotinamide.

[0009] To achieve the above objectives, the present invention adopts the following technical solution: A green synthesis process for nicotinamide based on a dual-active-site composite molecular sieve catalytic oxidation system includes the following steps: Step 1, Catalytic oxidation: Using 3-methylpyridine as raw material, a dual-active-site composite molecular sieve catalyst is added to a green oxidant and aqueous solvent system, and selective oxidation is carried out at 40-80℃ and atmospheric pressure to generate nicotinic acid intermediate; Step 2, in-situ ammoniation: After step 1 is completed, an ammonia source is directly added to the same reaction system, and in-situ amidation is completed under the conditions of 60-100℃ and 0.1-0.5 MPa with the help of the dual-active-site composite molecular sieve catalyst, to obtain a reaction solution containing crude nicotinamide. Step 3, Separation and Refining: The reaction solution is subjected to solid-liquid separation to recover the catalyst. The separated mother liquor is then concentrated, cooled and crystallized, and recrystallized to obtain a high-purity nicotinamide product. The dual-active-site composite molecular sieve catalyst is a core-shell bifunctional molecular sieve that simultaneously possesses alkyl selective oxidation active sites and ammoniation and amidation active sites. It is selected from any one or more of Fe-ZSM-5@MnO2, Cu-β@Co3O4, and Ni-MCM-41@CeO2 and used in combination.

[0010] Furthermore, the green oxidant is selected from any one or more of hydrogen peroxide aqueous solution, peroxytert-butanol, and sodium percarbonate in combination; the molar ratio of the green oxidant to 3-methylpyridine is 1.2 to 2.5:1.

[0011] Furthermore, when the hydrogen peroxide aqueous solution and peroxide tert-butanol are used in combination, the molar ratio of the two is 1:0.5 to 2; the sodium percarbonate is added in the form of an aqueous solution with a concentration of 5% to 20%.

[0012] Furthermore, the amount of the dual-active-site composite molecular sieve catalyst is 5% to 15% of the mass of the 3-methylpyridine raw material; the oxidation temperature in the catalytic oxidation step is 50 to 70°C, and the reaction time is 2 to 4 h; the ammoniation temperature in the in-situ ammoniation step is 70 to 90°C, the pressure is 0.2 to 0.4 MPa, and the ammoniation reaction time is 2 to 4 h; the total reaction time is 4 to 8 h; the catalytic oxidation and in-situ ammoniation are carried out continuously in series in the same closed reactor, without the need for intermediate separation and purification.

[0013] Furthermore, the ammonia source is selected from any one of liquid ammonia, concentrated ammonia water with a mass fraction of 25% to 28%, ammonium carbonate, and ammonium bicarbonate; the molar ratio of the ammonia source to 3-methylpyridine is 1.5 to 3.0:1.

[0014] Furthermore, the aqueous solvent is deionized water, or a mixture of ethanol and deionized water, and when a mixed solvent is used, the volume fraction of ethanol does not exceed 15%; the pH of the reaction system is controlled between 6.5 and 8.0 throughout the reaction; and the mass concentration of the 3-methylpyridine raw material is 10% to 30%.

[0015] Furthermore, the solid-liquid separation is carried out by filtration or magnetic separation; the separation and purification step adopts a low-temperature gradient crystallization process, concentrating the mother liquor to a nicotinamide mass fraction of 40% to 50%, crystallizing at 0 to 5°C for 2 to 4 hours, and then recrystallizing with pure water or an ethanol-water mixture after filtration. The resulting nicotinamide has a purity of not less than 99.5% and a total heavy metal content of less than 1 ppm.

[0016] Furthermore, the preparation method of the core-shell bifunctional molecular sieve is as follows: using Fe-ZSM-5, Cu-β or Ni-MCM-41 molecular sieve as the core, MnO2, Co3O4 or CeO2 nanoshells are loaded on its surface by co-precipitation or chemical vapor deposition, with a shell thickness of 2 to 10 nm, to obtain a core-shell bifunctional molecular sieve catalyst.

[0017] This invention also protects the nicotinamide product prepared by the above process, wherein the product has a purity of not less than 99.5%, a total heavy metal content of less than 1 ppm, a moisture content of not more than 0.3%, and an ash content of not more than 0.1%; and is applicable to the fields of pharmaceutical intermediates, food additives, cosmetic functional raw materials, and feed additives.

[0018] Finally, this invention also protects the application of the above-mentioned catalytic oxidation system in the industrial production of nicotinamide. Compared with the traditional nitric acid oxidation-stepwise ammoniation process, wastewater discharge is reduced by no less than 70%, nitrogen oxide emissions are reduced by no less than 80%, solid waste is reduced by no less than 60%, and the overall production cost is reduced by no less than 20%. It is suitable for both continuous and intermittent industrial production modes.

[0019] Compared with the prior art, the present invention has the following significant advantages: (1) Outstanding process innovation: This invention introduces multi-type dual-active-site core-shell composite molecular sieve catalysts into the nicotinamide synthesis system for the first time, breaking the traditional technical prejudice that oxidation and ammoniation must be carried out in steps and intermediates must be separated. Under the same reaction vessel and the same catalyst, the tandem coupling of catalytic oxidation and in-situ ammoniation is realized, shortening the process flow by more than 30% and reducing the number of operation units by 2 to 3 steps.

[0020] (2) Wide adaptability of catalytic system: By covering three core-shell bifunctional catalysts, Fe-ZSM-5@MnO2, Cu-β@Co3O4 and Ni-MCM-41@CeO2, it is also compatible with the single and combined use of three green oxidants, hydrogen peroxide, peroxytert-butanol and sodium percarbonate. It has a wide protection range and flexible process routes, providing a variety of alternative solutions for industrial-scale applications.

[0021] (3) Mild and green reaction conditions: The catalytic oxidation step is carried out in an aqueous phase system at atmospheric pressure of 40-80℃, and the in-situ ammoniation step is completed under low pressure conditions of 60-100℃ and not exceeding 0.5 MPa. There are no strong acid, strong alkali and strong corrosive media throughout the process. The equipment requirements are low, the safety is high, and the energy saving effect is significant.

[0022] (4) Excellent environmental benefits: The oxidation byproducts of green oxidants (H2O2, TBHP, SPC) are only water, tert-butanol or harmless carbonates, and do not produce NO. x Compared with the traditional nitric acid process, the emissions of waste gas and wastewater are reduced by more than 70%, nitrogen oxide emissions are reduced by more than 80%, and solid waste is reduced by more than 60%.

[0023] (5) Excellent catalyst recycling performance: The catalyst can be recovered by simple solid-liquid separation without high-temperature calcination regeneration. It can be recycled ≥10 times, and the catalytic activity retention rate is ≥90% after each cycle, which significantly reduces the cost of catalyst use.

[0024] (6) Excellent product quality: refined by low temperature gradient crystallization, the product purity is ≥99.5%, the total heavy metal content is <1ppm, the moisture content is ≤0.3%, and the ash content is ≤0.1%, which fully meets the quality requirements of pharmaceutical grade, food grade and cosmetic grade nicotinamide.

[0025] (7) Significant comprehensive economic benefits: The process flow is shortened, the catalyst is recyclable, the cost of treating waste is greatly reduced, and the comprehensive production cost is reduced by ≥20% compared with the traditional process, making it suitable for large-scale industrial promotion and application. Attached Figure Description

[0026] Figure 1 This is a flowchart of the nicotinamide synthesis process based on the dual-active-site composite molecular sieve catalytic oxidation system of the present invention.

[0027] Figure 2 This is a graph showing the trend of catalytic activity retention rate after the catalyst in Example 1 has been recycled 10 times.

[0028] Figure 3 This is a comparison of the HPLC purity spectra of the product from Example 1 and the product from Comparative Example 1.

[0029] Figure 4 The bar charts show the comparison of 3-methylpyridine conversion and nicotinamide selectivity in Examples 1-4 and Comparative Examples 1-3. Detailed Implementation

[0030] The technical solution of the present invention will be further described in detail below with reference to specific embodiments, so that those skilled in the art can fully understand the technical essence of the present invention, but it should not be construed as any limitation on the scope of protection of the present invention. In the following embodiments and comparative examples, unless otherwise specified, all chemicals used are analytical grade or industrial grade, conversion rate and selectivity are detected by high performance liquid chromatography (HPLC, internal standard method), product purity is determined by HPLC external standard method, and heavy metals are detected by ICP-MS.

[0031] Example 1 (1) Preparation of catalyst 10 g of commercial Fe-ZSM-5 molecular sieve (Si / Al=50, Fe content 2.5 wt%) was dispersed in 100 mL of deionized water and sonicated for 30 min to prepare a homogeneous suspension. Separately, 3.2 g of KMnO4 was dissolved in 50 mL of deionized water, and 2.8 g of MnSO4·H2O was dissolved in 30 mL of deionized water, serving as the oxidizing agent and reducing agent solutions, respectively. Both solutions were simultaneously and slowly added dropwise to the Fe-ZSM-5 suspension (dropping rate approximately 0.5 mL / min for each), maintaining the pH of the system at 7.0–7.5, and stirring at 25 °C for 4 h to allow MnO2 nanoparticles to grow in situ on the Fe-ZSM-5 surface. The catalyst was filtered, washed with deionized water until neutral, dried at 120℃ for 12 h, and calcined at 350℃ for 4 h to obtain a Fe-ZSM-5@MnO2 core-shell catalyst. The MnO2 shell thickness was approximately 4–6 nm, the Fe-ZSM-5:MnO2 mass ratio was approximately 85:15, and the BET specific surface area was approximately 320 m². 2 / g.

[0032] (2) Reagent preparation Catalyst: Fe-ZSM-5@MnO2 (prepared according to Catalyst Preparation Example 1, amount 7.4 g); Oxidant: 30% hydrogen peroxide aqueous solution (H2O2, analytical grade), the amount added is based on a molar ratio of H2O2:3-methylpyridine of 2.0:1, i.e., 226 mL (about 2.0 mol H2O2, equivalent to about 200 mL of 30% solution, density about 1.11 g / mL); Ammonia source: 25% concentrated ammonia water, the amount added is based on a molar ratio of NH3:3-methylpyridine of 2.0:1, i.e., about 204 mL (about 2.0 mol NH3).

[0033] (3) Process steps like Figure 1As shown, 93.1 g (1 mol) of 3-methylpyridine was added to a 500 mL four-necked flask equipped with a reflux condenser, along with 400 mL of deionized water and 7.4 g of Fe-ZSM-5@MnO2 catalyst. The mixture was stirred (300 rpm) and heated to 55 °C. Aqueous H2O2 was slowly added dropwise at a rate of approximately 0.5 mL / min using a peristaltic pump (the entire addition took approximately 60 min). The reaction was continued at 55 °C with stirring for a total of 3 h (starting from the initial addition of H2O2). HPLC was used to detect the conversion rate of 3-methylpyridine during the oxidation stage. Without separation, 25% concentrated ammonia was added directly to the system. The reactor was sealed, heated to 80 °C, and pressurized to 0.3 MPa with N2. The reaction was maintained at this temperature with stirring for 3 h. After cooling, the pressure was released, the reactor was opened, and HPLC was used to detect the formation of nicotinamide. The catalyst was separated by filtration. The mother liquor was concentrated, crystallized, recrystallized, and dried according to standard procedures to obtain white crystalline nicotinamide.

[0034] The test results are shown in Tables 1 and 2. Figure 2 : Table 1 Statistical Table of Process Efficiency Test Results ; Table 2. Statistical table of catalyst recycling data in this embodiment. ; Example 2 (1) Preparation of catalyst 10 g of Cu-β molecular sieve (Si / Al=25, Cu content 3.0 wt%) was dispersed in 100 mL of deionized water; 5.8 g of Co(NO3)2·6H2O was dissolved in 60 mL of deionized water and slowly added dropwise to the molecular sieve suspension; 0.5 mol / L NaOH solution was added dropwise under stirring until the pH reached 9.0, and the mixture was aged at 60℃ for 4 h to uniformly coat the Cu-β surface with a Co(OH)2 layer; the mixture was filtered, washed until neutral, dried at 110℃ for 12 h, and calcined at 400℃ for 4 h to decompose Co(OH)2 into Co3O4, thus obtaining a Cu-β@Co3O4 core-shell catalyst with a shell thickness of approximately 3–5 nm and a BET specific surface area of ​​approximately 280 m². 2 / g.

[0035] (2) Reagent preparation Catalyst: Cu-β@Co3O4 (prepared according to catalyst preparation example 2, amount 7.4 g); Oxidant: peroxytert-butanol (TBHP, 70% aqueous solution), based on a TBHP:3-methylpyridine molar ratio of 2.0:1; Ammonia source: liquid ammonia, based on an NH3:3-methylpyridine molar ratio of 2.0:1 (approximately 34 g, filled into a sealed reactor by a 0.5 MPa steel cylinder).

[0036] (3) Process steps 93.1 g (1 mol) of 3-methylpyridine and 400 mL of deionized water were added to a 1 L high-pressure reactor. 7.4 g of Cu-β@Co3O4 catalyst and 2 mol (equivalent to 241 g) of 70% TBHP aqueous solution were added. The mixture was stirred and heated to 60 °C and reacted at atmospheric pressure for 3 h (catalytic oxidation stage). Without opening the reactor, the temperature was lowered to 50 °C, and 34 g (2 mol) of liquid ammonia was introduced. The reactor was sealed, heated to 80 °C, and pressurized to 0.3 MPa. The mixture was stirred and kept at this temperature for 3 h (in-situ ammoniation stage). The reactor was cooled and depressurized, and the product was discharged. The catalyst was recovered by filtration, and the mother liquor was purified according to a general process.

[0037] The test results are shown in Table 3: Table 3 Statistical Table of Process Efficiency Test Results ; In this embodiment, TBHP is used as the oxidant, and its byproduct is tert-butanol, which can be recovered and recycled from wastewater through distillation, further reducing the environmental impact.

[0038] Example 3 (1) Preparation of catalyst 10 g of Ni-MCM-41 molecular sieve (pore size approximately 3 nm, Ni content 2.0 wt%) was dispersed in 100 mL of deionized water; 8.7 g of Ce(NO3)3·6H2O was dissolved in 80 mL of deionized water and ultrasonically impregnated onto the surface of Ni-MCM-41, stirred for 2 h; an appropriate amount of ammonia was slowly added to adjust the pH to 9.0, allowing Ce(OH)3 to be uniformly deposited; the catalyst was hydrothermally treated at 100℃ for 6 h, filtered, washed, dried at 110℃ for 12 h, and calcined at 500℃ for 5 h to obtain a Ni-MCM-41@CeO2 core-shell catalyst with a CeO2 shell thickness of approximately 5–8 nm and a BET specific surface area of ​​approximately 450 m². 2 / g.

[0039] (2) Reagent preparation Catalyst: Ni-MCM-41@CeO2 (prepared according to catalyst preparation example 3, amount 7.4 g); Oxidant: Sodium percarbonate (SPC, Na2CO3·1.5H2O2, effective active oxygen content about 13.5%), based on a molar ratio of SPC:3-methylpyridine of 2.0:1 (based on effective oxygen in H2O2), about 271 g of SPC was added; Ammonia source: Ammonium carbonate ((NH4)2CO3), based on a molar ratio of NH3 equivalent to 3-methylpyridine of 2.0:1, 96 g of ammonium carbonate was added (about 1 mol (NH4)2CO3, equivalent to 2 mol NH3).

[0040] (3) Process steps 3-Methylpyridine (93.1 g, 1 mol), 400 mL of deionized water, and 7.4 g of Ni-MCM-41@CeO2 catalyst were added to a four-necked flask. SPC solid was added in batches (four times, every 30 min to avoid local over-oxidation). The mixture was stirred at 55°C and atmospheric pressure for 3 h (catalytic oxidation stage). The temperature was raised to 75°C, and 96 g of ammonium carbonate was added. The flask was sealed, and the temperature was controlled at 80°C and 0.2 MPa (generated by CO2 decomposition; the system was kept at a slightly positive pressure by controlling the slow decomposition of ammonium carbonate). The mixture was kept at this temperature for 3 h (in-situ ammoniation stage). The mixture was cooled, filtered to recover the catalyst, and the mother liquor was purified.

[0041] The test results are shown in Table 4: Table 4 Statistical Table of Process Efficiency Test Results ; In this embodiment, the byproduct of sodium percarbonate is harmless sodium carbonate. The ammonium carbonate ammonia source decomposes to generate ammonia and CO2. There is no need to treat toxic and harmful substances in the wastewater, and the COD of the wastewater is reduced by about 65%, resulting in outstanding environmental benefits.

[0042] Example 4 (1) Reagent preparation Catalyst: Fe-ZSM-5@MnO2 and Cu-β@Co3O4 were mixed in a mass ratio of 1:1, with a total dosage of 7.4 g (3.7 g each); Oxidant: 30% hydrogen peroxide aqueous solution and 70% TBHP were mixed in a molar ratio of 1:1, with a total effective oxygen content to raw material molar ratio of 2.0:1; Ammonia source: 25% concentrated ammonia water, with the dosage the same as in Example 1; Other parameters were the same as general process conditions.

[0043] (2) Operating steps 3-Methylpyridine, 400 mL of deionized water, and the compound catalyst were added to the reactor and stirred until the temperature reached 55°C. Simultaneously, H2O2 aqueous solution and TBHP were added dropwise using two peristaltic pumps (the flow rate was controlled at a 1:1 molar ratio). The addition was completed in 60 min, and the reaction was continued at 55°C for a total of 3 h. Without opening the reactor, 25% concentrated ammonia was added, and the temperature was raised to 80°C at 0.3 MPa. The reaction was maintained for 3 h. After cooling, filtration, and purification, the final product was obtained.

[0044] The test results are shown in Table 5: Table 5 Statistical Table of Process Efficiency Test Results ; In this embodiment, the synergistic effect of catalyst and oxidant combination achieves optimal conversion rate and selectivity, further improves catalyst cycle stability, and has the best overall performance among all embodiments.

[0045] Example 5 This example investigates the effect of different catalyst dosages (5%, 8%, 12%, and 15%, all of which are percentages of raw material mass) on reaction performance. The catalyst used is Fe-ZSM-5@MnO2, and the other parameters are the same as the general process conditions (conditions of Example 1).

[0046] The test results are shown in Table 6: Table 6. Statistical Table of Process Efficiency Test Results for Different Catalyst Doses ; Conclusion: When the catalyst dosage is 8% of the raw material mass, the overall performance and cost are optimal; increasing it to 12%–15% results in limited performance improvement and is not economical; below 5%, the conversion rate decreases significantly. The preferred dosage range is 6%–12% of the raw material mass.

[0047] Example 6 This example investigates the effect of oxidation temperature (40℃, 50℃, 55℃, 65℃, 80℃) on the performance of the catalytic oxidation step, with other parameters being the same as the general process (Example 1).

[0048] The test results are shown in Table 7: Table 7 Statistical Table of Process Efficiency Test Results at Different Oxidation Temperatures ; Conclusion: The oxidation temperature of 55℃ yields the best overall performance, with the highest selectivity for nicotinic acid and the fewest byproducts. Temperatures that are too low (40℃) result in a slow reaction rate and low conversion rate; temperatures that are too high (80℃) accelerate the decomposition of H2O2 and increase the number of peroxidation side reactions. The preferred oxidation temperature range is 50–65℃.

[0049] Example 7 (Effect of pH on the reaction) This embodiment investigates the effect of pH on the synthesis of nicotinamide. The catalyst is Fe-ZSM-5@MnO2, and other parameters are the same as in the general process. pH is adjusted by phosphate buffer solution, rather than by direct adjustment with strong acids or bases.

[0050] The test results are shown in Table 8: Table 8 Statistical Table of Process Efficiency Test Results at Different pH Values ; Conclusion: Near-neutral conditions (pH 6.5–8.0) are most favorable for the catalytic system of this invention. Acidity or strong alkalinity both lead to decreased catalyst stability and selectivity. The preferred pH range is 6.8–7.5.

[0051] Comparative Example 1 (Traditional Nitric Acid Oxidation-Stepwise High-Pressure Ammoniation Process) Operating steps Step 1: Add 93.1 g, 1 mol of 3-methylpyridine to a high-pressure stainless steel reactor, add fuming nitric acid (HNO3, 65%, 1.5 mol) and 0.1 mol of 70% sulfuric acid (co-catalyst), seal, heat to 230℃, purge with N2 to a total pressure of 5 MPa, and maintain the temperature for 4 h; cool, open the reactor, collect the reaction liquid containing nicotinic acid, filter to remove solid byproducts, recover unreacted nitric acid by vacuum distillation, evaporate and concentrate, cool to crystallize, filter, recrystallize with pure water to obtain nicotinic acid intermediate, and dry.

[0052] Step 2: Transfer the above nicotinic acid intermediate to another high-pressure reactor, add liquid ammonia (2 mol), seal, heat to 250℃, pressurize to 8 MPa, and keep the reaction at this temperature for 6 h; cool and depressurize, remove ammonia by vacuum distillation, concentrate and crystallize, recrystallize, and dry to obtain the nicotinamide product.

[0053] The test results are shown in Table 9. Figure 3 : Table 9 Statistical Table of Process Comparison Results ; Comparative Example 2 (Monofunctional catalyst + hydrogen peroxide, stepwise reaction) Commercial ZSM-5 molecular sieve (without metal modification and without core-shell dual active sites) was used as a monofunctional oxidation catalyst, with a dosage of 7.4 g. 3-methylpyridine (1 mol) was first oxidized at 55℃ with 30% H2O2 (2 mol) for 3 h (oxidation stage). The catalyst was then removed, and 7.4 g of commercial alumina-supported NiO ammoniation catalyst was added, along with 25% concentrated ammonia (2 mol). The temperature was raised to 80℃ and maintained at 0.3 MPa for 3 h (ammoniation stage). The mixture was then filtered and purified.

[0054] The test results are shown in Table 10: Table 10 Statistical Table of Process Comparison Results ; Analysis: Ordinary ZSM-5 molecular sieves lack core-shell dual active sites and cannot simultaneously catalyze oxidation and ammoniation. They must be carried out stepwise with two different catalysts, which is a complex process. Furthermore, the catalyst has poor cycle stability (the activity drops to 74.3% after 5 cycles), which is far inferior to the core-shell bifunctional catalyst of this invention (the activity remains at 92.5% after 10 cycles).

[0055] Comparative Example 3 (no core-shell structure, single molecular sieve, in-situ ammoniation attempt) The same experimental parameters and process flow as in Example 1 were used, but the catalyst was replaced with a core-shell-free commercial H-ZSM-5 molecular sieve (without metal active sites) in an amount of 7.4 g. In situ ammoniation one-pot method was attempted in the same reaction system, and the remaining parameters were completely the same as the general process.

[0056] The test results are shown in Table 11: Table 11 Statistical Table of Process Comparison Results ; Analysis: Ordinary H-ZSM-5 molecular sieves lack core-shell dual active sites (no oxide metal sites, no ammoniation metal sites). Although the acidity of the framework can provide certain catalytic activity, it cannot synergistically catalyze the two-step reactions of oxidation and ammoniation, resulting in low conversion rate, poor selectivity, and many by-products. It cannot meet the requirements of industrial production of high-purity nicotinamide, which fully demonstrates the key technical value of the dual active site core-shell catalyst of this invention.

[0057] Summary of comprehensive comparative data: ; From the above table and Figure 4 In summary, the 3-methylpyridine conversion rate of Examples 1-4 of this invention is all above 95%, the nicotinamide selectivity is all above 89%, the total yield is all above 85%, the product purity is all not less than 99.5%, the heavy metal content is all less than 1 ppm, and the catalyst activity retention rate after 10 cycles is all not less than 90%. In contrast, the three comparative examples are significantly lower than the examples of this invention in all the above key indicators. In particular, the total yield of the traditional nitric acid oxidation method (Comparative Example 1) is only 66.7%, the heavy metal content of the product is as high as 4.85 ppm (5 times higher than the pharmaceutical grade limit), and the wastewater discharge is as high as 3.5 times that of this invention. This fully demonstrates the innovation, advancement, and practicality of the technical solution of this invention.

Claims

1. A green synthesis process for nicotinamide based on a dual-active-site composite molecular sieve catalytic oxidation system, characterized in that, Includes the following steps: Step 1, Catalytic oxidation: Using 3-methylpyridine as raw material, a dual-active-site composite molecular sieve catalyst is added to a green oxidant and aqueous solvent system, and selective oxidation is carried out at 40-80℃ and atmospheric pressure to generate nicotinic acid intermediate; Step 2, in-situ ammoniation: After step 1 is completed, an ammonia source is directly added to the same reaction system, and in-situ amidation is completed under the conditions of 60-100℃ and 0.1-0.5 MPa with the help of the dual-active-site composite molecular sieve catalyst, to obtain a reaction solution containing crude nicotinamide. Step 3, Separation and Refining: The reaction solution is subjected to solid-liquid separation to recover the catalyst. The separated mother liquor is then concentrated, cooled and crystallized, and recrystallized to obtain a high-purity nicotinamide product. The dual-active-site composite molecular sieve catalyst is a core-shell bifunctional molecular sieve that simultaneously possesses alkyl selective oxidation active sites and ammoniation and amidation active sites. It is selected from any one or more of Fe-ZSM-5@MnO2, Cu-β@Co3O4, and Ni-MCM-41@CeO2 and used in combination.

2. The green synthesis process for nicotinamide according to claim 1, characterized in that, The green oxidant is selected from any one or more of hydrogen peroxide aqueous solution, peroxytert-butanol, and sodium percarbonate in combination; the molar ratio of the green oxidant to 3-methylpyridine is 1.2 to 2.5:

1.

3. The green synthesis process for nicotinamide according to claim 2, characterized in that, When the hydrogen peroxide aqueous solution and peroxide tert-butanol are used in combination, the molar ratio of the two is 1:0.5 to 2; when the sodium percarbonate is used, it is added in the form of an aqueous solution with a concentration of 5% to 20%.

4. The green synthesis process for nicotinamide according to claim 1, characterized in that, The amount of the dual-active-site composite molecular sieve catalyst is 5% to 15% of the mass of the 3-methylpyridine raw material; the oxidation temperature in the catalytic oxidation step is 50 to 70°C, and the reaction time is 2 to 4 h; the ammoniation temperature in the in-situ ammoniation step is 70 to 90°C, the pressure is 0.2 to 0.4 MPa, and the ammoniation reaction time is 2 to 4 h; the total reaction time is 4 to 8 h; the catalytic oxidation and in-situ ammoniation are carried out continuously in series in the same closed reactor, without the need for intermediate separation and purification.

5. The green synthesis process for nicotinamide according to claim 1, characterized in that, The ammonia source is selected from any one of liquid ammonia, concentrated ammonia water with a mass fraction of 25% to 28%, ammonium carbonate, and ammonium bicarbonate; the molar ratio of the ammonia source to 3-methylpyridine is 1.5 to 3.0:

1.

6. The green synthesis process for nicotinamide according to claim 1, characterized in that, The aqueous solvent is deionized water or a mixture of ethanol and deionized water. When a mixed solvent is used, the volume fraction of ethanol does not exceed 15%. The pH of the reaction system is controlled between 6.5 and 8.0 throughout the reaction. The mass concentration of 3-methylpyridine raw material is 10% to 30%.

7. The green synthesis process for nicotinamide according to claim 1, characterized in that, The solid-liquid separation is carried out by filtration or magnetic separation; the separation and purification step adopts a low-temperature gradient crystallization process, concentrating the mother liquor to a nicotinamide mass fraction of 40% to 50%, crystallizing at 0 to 5°C for 2 to 4 hours, and then recrystallizing with pure water or an ethanol-water mixture after filtration. The resulting nicotinamide has a purity of not less than 99.5% and a total heavy metal content of less than 1 ppm.

8. The green synthesis process for nicotinamide according to claim 1, characterized in that, The preparation method of the core-shell bifunctional molecular sieve is as follows: using Fe-ZSM-5, Cu-β or Ni-MCM-41 molecular sieve as the core, MnO2, Co3O4 or CeO2 nanoshells are loaded on its surface by co-precipitation or chemical vapor deposition, with a shell thickness of 2 to 10 nm, to obtain the core-shell bifunctional molecular sieve catalyst.

9. A nicotinamide product prepared by the process described in any one of claims 1 to 8, characterized in that, The product has a purity of not less than 99.5%, a total heavy metal content of less than 1 ppm, a moisture content of not more than 0.3%, and an ash content of not more than 0.1%; it is suitable for use in pharmaceutical intermediates, food additives, cosmetic functional ingredients, and feed additives.

10. The application of the catalytic oxidation system according to any one of claims 1 to 8 in the industrial production of nicotinamide, characterized in that, Compared with the traditional nitric acid oxidation-stepwise ammoniation process, wastewater discharge is reduced by no less than 70%, nitrogen oxide emissions are reduced by no less than 80%, solid waste is reduced by no less than 60%, and overall production costs are reduced by no less than 20%; it is suitable for both continuous and intermittent industrial production modes.

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