Process for the preparation of sodium ketovalelate

Abstract

This invention discloses a method for preparing sodium ketovaline, belonging to the field of chemical synthesis technology, including the following steps: using hydantoin and acetone as raw materials, and using a solid base catalyst K / MgAlO x Using sodium hydroxide as the main catalyst and a solvent as the co-catalyst, a condensation reaction is carried out in the presence of a solvent. After the condensation reaction is completed, a certain amount of sodium hydroxide is added, and the hydrolysis reaction is continued under the catalysis of a solid base catalyst to prepare sodium ketovaline. This invention can effectively improve the yield of sodium ketovaline, and the catalyst can be recycled.

Description

Technical Field

[0001] This invention relates to a method for preparing sodium ketovaline, belonging to the field of chemical synthesis technology. Background Technology

[0002] Ketovaline sodium, chemically known as sodium 3-methyl-2-oxobutyrate, has the molecular formula C5H7NaO3 and the following structural formula:

[0003] .

[0004] Ketovaline sodium is a very important branched-chain ketoacid (BCKA). Compared with its corresponding amino acid (valine), it has unique metabolic characteristics and health benefits. Its applications are mainly focused on high-end medical nutrition and sports nutrition. Currently, it is mainly used for nutritional therapy for patients with chronic kidney disease and dialysis.

[0005] Regarding the synthesis of sodium ketovaline, multiple synthetic routes have been reported both domestically and internationally, mainly including the low-temperature alkaline catalysis method, the solid alkaline catalytic hydrolysis method, and the bioenzyme catalysis method.

[0006] There are currently three synthetic routes for preparing sodium ketovaline: (1) Hydantoin low-temperature alkaline catalysis: Sodium ketovaline is synthesized by condensation of hydantoin and acetone at low temperature, hydrolysis by heating, pH adjustment and crystallization. This is the mainstream method at present. The raw materials are readily available and the operation is simple, but it will generate a large amount of waste liquid. The problem of waste liquid still needs to be solved. (2) Solid alkaline catalytic hydrolysis: Sodium ketovaline is synthesized by isopropylidene hydantoin under the catalysis of solid alkaline catalyst PDVB-SO3Na. This reduces the amount of acid and alkali used in the preparation of sodium ketovaline. (3) Bioenzyme catalysis: L-amino acid deaminase (L-AAD) specifically catalyzes the oxidation and deamination of L-valine to generate the corresponding α-ketoisovaleric acid. Then, sodium ketovaline is obtained by alkaline salt formation.

[0007] Patents CN106045843A and CN110627637A describe a process where hydantoin reacts with ketones to produce 2-butylenehydantoin, which is then hydrolyzed with sodium hydroxide to yield ketone isoleucine. This process solves the problems of uncontrollable production, high cost, and significant environmental impact associated with existing production processes of branched-chain keto acids. However, it still generates a large amount of waste liquid, and the synthesis of 2-butylenehydantoin requires a significant amount of monoethanolamine as a catalyst, raising concerns about monoethanolamine recovery and safety.

[0008] Patent CN113735727A describes a process where hydantoin and butanone react in ammonia water to produce sec-butylhydantoin. A strong base is then added, allowing for a high-yield, high-purity reaction of racemic ketone isoleucine without complex post-processing steps. The reaction is promoted under slight negative pressure, and the generated ammonia is recovered and reused as a catalyst, achieving recycling. While ammonia water, which is relatively easy to recover and reuse, is used as a catalyst for the preparation of 2-butylhydantoin, the cost and losses remain significant.

[0009] Patent CN103044238A describes a process where diethyl oxalate is added dropwise to an alcoholic solution of sodium alkoxide, followed by the addition of 2-methylbutyraldehyde. The mixture is kept at a constant temperature with stirring, and then an alkaline solution is added. After the temperature is maintained, the solution is adjusted to acid, extracted, and the extract is then added to a certain amount of water. Finally, an alkaline solution is added to adjust the pH to obtain sodium ketovaline. This reaction uses the hazardous reagent sodium alkoxide, and generates a large amount of waste liquid, which is not conducive to industrial production.

[0010] Patent CN116891406A describes the preparation of sodium ketovaline using the solid base catalyst PDVB-SO3Na, with isopropylidene hydantoin and sodium hydroxide as raw materials. This reduces the amount of sodium hydroxide and sulfuric acid used, increases the yield, enables catalyst recycling, simplifies the process, and improves production efficiency and economy. The -SO3 groups on the surface provide Brønsted basicity (moderate strength), which is relatively difficult for catalytic condensation reactions, requiring a stronger solid base catalyst.

[0011] Currently, the preparation of sodium ketovaline mainly involves the condensation of hydantoin and acetone under the catalysis of an organic or inorganic base to obtain 2-propylidene hydantoin, followed by hydrolysis of 2-propylidene hydantoin in sodium hydroxide solution to yield sodium ketovaline. Experiments have shown that the presence of an organic base in the system interferes with the hydrolysis process, causing excessive hydrolysis of ketovaline to isopropionic acid, thus preventing the preparation of sodium ketovaline. Furthermore, using ammonia and inorganic bases alone has poor catalytic effects, resulting in almost no reaction. In addition, this process generates a large amount of waste liquid, leading to high environmental costs. Summary of the Invention

[0012] The present invention aims to provide a method for preparing sodium ketovaline with high yield and recyclable catalyst.

[0013] The technical solution adopted in this invention is as follows:

[0014] A method for preparing sodium ketovaline includes the following steps: using hydantoin and acetone as raw materials, and using a solid base catalyst K / MgAlO x The main catalyst, sodium hydroxide, is used as a co-catalyst to carry out a condensation reaction in the presence of a solvent. After the condensation reaction is completed, a certain amount of sodium hydroxide is added, and the hydrolysis reaction is carried out under the catalysis of a solid base catalyst to prepare sodium ketovaline.

[0015] This invention provides a method for preparing sodium ketovaline, using a solid base catalyst K / MgAlO x Under catalysis, hydantoin, acetone and sodium hydroxide first undergo a condensation reaction at a lower temperature. After the reaction is complete, the temperature is directly increased to carry out a hydrolysis reaction, thereby effectively reducing the amount of alkali used and increasing the yield of sodium ketovaline.

[0016] Further settings include:

[0017] The condensation and hydrolysis reactions are carried out using a one-pot process. That is, after the condensation reaction in the first step is completed, sodium hydroxide in stoichiometric ratio is added directly without any treatment to carry out the hydrolysis reaction and prepare sodium ketovaline. The one-pot process can achieve better economic benefits.

[0018] The solid base catalyst K / MgAlO x (x=1~1.5) was prepared by the following method: magnesium salt, aluminum salt, and potassium salt were dissolved in deionized water, then a precipitant was added to precipitate them. After adjusting to the target pH, stirring and aging were continued. The mixture was then filtered, washed, and vacuum dried to obtain a solid. After grinding into a fine powder, the solid was placed in a tube furnace for calcination. After calcination, the powder was cooled to room temperature to obtain the solid base catalyst K / MgAlO. x .

[0019] The magnesium salt is preferably magnesium nitrate.

[0020] The aluminum salt is preferably aluminum nitrate.

[0021] The potassium salt is preferably either potassium nitrate or potassium carbonate.

[0022] The precipitant is preferably any one of ammonia, urea, and sodium hydroxide.

[0023] The molar ratio of the magnesium salt, aluminum salt, and potassium salt is Mg:Al:K = 1 to 5:1:0.025 to 0.075, preferably Mg:Al:K = 3:1:0.05.

[0024] The calcination process involves calcining at 400-600℃ for 2-6 hours in an argon atmosphere, preferably at 500℃ for 4 hours in an argon atmosphere.

[0025] In the condensation reaction, the solid base catalyst K / MgAlO x The dosage of the catalyst is 1-10 wt% of hydantoin, and the preferred dosage of the catalyst is 5-10 wt% of hydantoin.

[0026] In the condensation reaction, the amount of sodium hydroxide co-catalyst is 5-10 wt% of hydantoin, preferably 10 wt% of hydantoin.

[0027] In the condensation reaction, the solvent can be either water or an aqueous ethanol solution.

[0028] In the condensation reaction, the reaction temperature is 80℃ and the reaction time is 8 hours.

[0029] In the hydrolysis reaction, the reaction temperature is 100℃ and the reaction time is 8 hours.

[0030] In the hydrolysis reaction, the mass ratio of sodium hydroxide to hydantoin is 1:1-2.

[0031] Preferably, the solid base catalyst K / MgAlO x It can be recycled. Specifically, after the reaction is completed, the temperature is lowered to room temperature, the catalyst is recovered by centrifugation, the catalyst is washed several times with ethanol and water, dried, and the reaction is carried out again.

[0032] The beneficial effects of this invention are as follows:

[0033] This invention prepares a novel solid base catalyst K / MgAlO x This catalyst, used for the catalytic synthesis of sodium ketovaline, features highly dispersed single-atom potassium active sites with strong electron-donating ability and super-basicity. Its high specific surface area and abundant pore structure provide a large reaction space, facilitating the diffusion and adsorption of reactants (hydantoin and acetone). The strong basicity sites can more effectively activate the highly acidic NH functional groups in the hydantoin molecule, generating highly reactive nitrogen anions, thereby significantly lowering the energy barrier for the condensation reaction with acetone. This may allow the reaction to achieve higher conversion rates under milder conditions (lower temperature and shorter time). Furthermore, anchoring the single-atom potassium to a robust support through strong chemical bonds effectively prevents the leaching and loss of basic components during the liquid-phase reaction, a common cause of deactivation in many basic catalysts (such as K₂CO₃ / Al₂O₃). This significantly reduces metal leaching and agglomeration, enabling repeated recycling dozens of times with essentially unchanged catalyst activity. This is of great significance for reducing reaction costs and making it suitable for large-scale industrial production.

[0034] The following accompanying drawings and specific embodiments will enable those skilled in the art to more fully understand the present invention, but do not limit the invention in any way. Attached Figure Description

[0035] Figure 1 The image shows the XRD pattern of the solid base catalyst prepared in the embodiments of the present invention.

[0036] Figure 2 The solid base catalyst prepared in the embodiments of the present invention and the comparative sample hydrotalcite MgAlO x The fine spectrum of XPS O 1s.

[0037] Figure 3 The XPS spectra of the solid base catalyst prepared in the embodiments of the present invention and the comparative sample of pure potassium carbonate are fine K 2p spectra.

[0038] Figure 4 The diagram shows the catalytic effects of different types of catalysts applied to the preparation of sodium ketovaline.

[0039] Figure 5 The cycling performance of the solid base catalyst prepared in this invention is shown. Detailed Implementation

[0040] The following detailed description of specific embodiments of the present invention, in conjunction with the accompanying drawings, does not limit the scope of the claims. Unless otherwise specified, the raw materials and reagents used in the embodiments of the present invention are all prior art or commercially available products.

[0041] The solid base catalyst used in the following embodiments of the present invention is prepared by the following method:

[0042] Mg(NO3)2·6H2O (19.23 g), Al(NO3)3·9H2O (9.38 g), and KNO3 (0.13 g) were dissolved in 200 mL of deionized water and dispersed by stirring at room temperature for 2 h. Then, 25 wt% ammonia solution was added dropwise to the above solution to adjust the pH to about 10.5, and the mixture was stirred overnight at room temperature. The solid was collected by centrifugation, washed several times with water and ethanol, and then vacuum dried at 50 °C overnight. The dried solid was placed in a tube furnace and calcined at 500 °C for 4 h under an argon atmosphere at a heating rate of 5 °C / min. After cooling to room temperature, the solid base catalyst K / MgAlO3 was obtained. x , labeled as catalyst 1.

[0043] Catalyst characterization:

[0044] Figure 1 The aforementioned solid base catalyst K / MgAlO x The XRD pattern of the K / MgAlO2 catalyst was compared with that of the standard MgO card, and we found that the solid base catalyst K / MgAlO2 prepared in this invention... x The diffraction peaks were mainly MgO, which may be due to the large magnesium-aluminum ratio. Aluminum exists in a relatively dispersed form in the magnesium oxide lattice. In addition, we did not find any diffraction peaks related to potassium, which may also be extremely dispersed.

[0045] Figure 2 The solid base catalyst K / MgAlO prepared for x And the control sample hydrotalcite MgAlO x The fine O 1s spectrum of XPS. Figure 2 We can find that: solid base catalyst K / MgAlOx and MgAlO x Hydrotalcites all contain lattice oxygen, defect oxygen, and adsorbed oxygen, and MgAlO x The high content of defect oxygen in hydrotalcite makes it more favorable for substrate adsorption, thus improving catalytic reactions. Furthermore, the introduction of single-atom potassium partially repairs defect oxygen, increasing the lattice oxygen / defect oxygen ratio. We also observed that the low electronegativity of alkali metals creates novel strong basic sites (KOMs), with the corresponding O 1s peak appearing at a low binding energy (~528.5 eV). This new peak reconstructs the surface chemical environment, rather than simply modifying the existing one. Additionally, the strong CO2 adsorption of potassium leads to an increase in the K / MgAlO2 ratio. x The adsorbed oxygen content increases.

[0046] Figure 3 The solid base catalyst K / MgAlO prepared in this invention x The fine XPS K 2p spectrum of pure potassium carbonate was compared with that of the control sample. This is because K is present in a highly dispersed single-atom form with MgAlO₂. x When strong interactions occur in the support, its electronic environment changes significantly, leading to the following changes in the K 2p spectrum: K / MgAlO x Compared to potassium carbonate, the binding energy of K 2p shifts to a lower direction; the full width at half maximum (FWHM) of the K 2p peak narrows, and the peak shape becomes more symmetrical and sharper. In contrast, the chemical environment of K 2CO 3 particles or polycrystalline phases is relatively less homogeneous, resulting in a broader peak shape.

[0047] Example 1

[0048] Add 100g hydantoin, 70g acetone, 5g catalyst 1, 10g sodium hydroxide, and 300g water to a reaction flask, heat to 80℃, and react for 8 hours. After the reaction is complete, cool to room temperature, add 50g sodium hydroxide, and continue to heat to 100℃ for another 8 hours. After the reaction is complete, cool to room temperature, filter and collect the solution. HPLC calculation shows that the conversion rate of hydantoin is 95% and the selectivity of ketovaline sodium is 90%. 1 H NMR (400 MHz, Deuterium Oxide) δ 3.22 (m, J = 7.0 Hz, 1H), 1.04 (d,J = 6.7 Hz, 6H).

[0049] Example 2

[0050] This example mainly examines the effect of the catalyst on the reaction.

[0051] The preparation method is the same as in Example 1, except that catalyst 1 is replaced with catalyst 2 to catalyst 9, and the effect of the catalyst on the reaction conversion rate and selectivity is investigated.

[0052] Catalyst 2-Catalyst 3: Adjust the amount of KNO3.

[0053] Mg(NO3)2·6H2O (19.23 g), Al(NO3)3·9H2O (9.38 g), and KNO3 (0.26 g) were dissolved in 200 mL of deionized water and dispersed by stirring at room temperature for 2 h. Then, 25 wt% ammonia solution was added dropwise to the above solution to adjust the pH to about 10.5, and the mixture was stirred overnight at room temperature. The solid was collected by centrifugation, washed several times with water and ethanol, and then vacuum dried at 50 °C overnight. The dried solid was placed in a tube furnace and calcined at 500 °C for 4 h under an argon atmosphere at a heating rate of 5 °C / min. After cooling to room temperature, the catalyst K / MgAlO was obtained. x , labeled as catalyst 2.

[0054] Mg(NO3)2·6H2O (19.23 g), Al(NO3)3·9H2O (9.38 g), and KNO3 (0.065 g) were dissolved in 200 mL of deionized water and dispersed by stirring at room temperature for 2 h. Then, 25 wt% ammonia solution was added dropwise to the above solution to adjust the pH to approximately 10.5, and the mixture was stirred overnight at room temperature. The solid was collected by centrifugation, washed several times with water and ethanol, and then vacuum dried overnight at 50 °C. The dried solid was placed in a tube furnace and calcined at 500 °C for 4 h under an argon atmosphere at a heating rate of 5 °C / min. After cooling to room temperature, the catalyst K / MgAlO was obtained. x , labeled as catalyst 3.

[0055] Catalysts 4-5: Adjust the magnesium-aluminum ratio

[0056] Mg(NO3)2·6H2O (21.33 g), Al(NO3)3·9H2O (6.25 g), and KNO3 (0.13 g) were dissolved in 200 mL of deionized water and dispersed by stirring at room temperature for 2 h. Then, 25 wt% ammonia solution was added dropwise to the above solution to adjust the pH to about 10.5, and the mixture was stirred overnight at room temperature. The solid was collected by centrifugation, washed several times with water and ethanol, and then vacuum dried at 50 °C overnight. The dried solid was placed in a tube furnace and calcined at 500 °C for 4 h under an argon atmosphere at a heating rate of 5 °C / min. After cooling to room temperature, the catalyst K / MgAlO was obtained. x , labeled as catalyst 4.

[0057] Mg(NO3)2·6H2O (12.8 g), Al(NO3)3·9H2O (18.75 g), and KNO3 (0.13 g) were dissolved in 200 mL of deionized water and dispersed by stirring at room temperature for 2 h. Then, 25 wt% ammonia solution was added dropwise to the above solution to adjust the pH to about 10.5, and the mixture was stirred overnight at room temperature. The solid was collected by centrifugation, washed several times with water and ethanol, and then vacuum dried at 50 °C overnight. The dried solid was placed in a tube furnace and calcined at 500 °C for 4 h under an argon atmosphere at a heating rate of 5 °C / min. After cooling to room temperature, the catalyst K / MgAlO was obtained. x , labeled as catalyst 5.

[0058] Catalyst 6: Adjusting the potassium salt type

[0059] Mg(NO3)2·6H2O (19.23 g), Al(NO3)3·9H2O (9.38 g), and K2CO3 (0.09 g) were dissolved in 200 mL of deionized water and dispersed by stirring at room temperature for 2 h. Then, 25 wt% ammonia solution was added dropwise to the above solution to adjust the pH to about 10.5, and the mixture was stirred overnight at room temperature. The solid was collected by centrifugation, washed several times with water and ethanol, and then vacuum dried at 50 °C overnight. The dried solid was placed in a tube furnace and calcined at 500 °C for 4 h under an argon atmosphere at a heating rate of 5 °C / min. After cooling to room temperature, the catalyst K / MgAlO was obtained. x , labeled as catalyst 6.

[0060] Catalysts 7-8: Adjusting the precipitant

[0061] 19.23 g of Mg(NO3)2·6H2O, 9.38 g of Al(NO3)3·9H2O, and 0.13 g of KNO3 were dissolved in 200 mL of deionized water and dispersed by stirring at room temperature for 2 h. Then, 1.0 M NaOH solution was slowly added dropwise to the above solution to adjust the pH to about 10.5, and the mixture was stirred overnight at room temperature. The solid was collected by centrifugation, washed several times with water and ethanol, and then vacuum dried at 50 °C overnight. The dried solid was placed in a tube furnace and calcined at 500 °C for 4 h under an argon atmosphere at a heating rate of 5 °C / min. After cooling to room temperature, the catalyst K / MgAlO was obtained. x , marked as catalyst 7.

[0062] Mg(NO3)2·6H2O (19.23 g), Al(NO3)3·9H2O (9.38 g), and KNO3 (0.13 g) were dissolved in 200 mL of deionized water and stirred for 2 h at room temperature. Then, urea (60 g) was added to the solution and dissolved completely. The mixture was then heated to 80 °C and stirred for 12 h. The solid was collected by centrifugation, washed several times with water and ethanol, and then vacuum dried overnight at 50 °C. The dried solid was then calcined in a tube furnace at 500 °C for 4 h under an argon atmosphere at a heating rate of 5 °C / min. After cooling to room temperature, the catalyst K / MgAlO was obtained. x , marked as catalyst 8.

[0063] Catalyst 9: No potassium salt added

[0064] 19.23 g of Mg(NO3)2·6H2O and 9.38 g of Al(NO3)3·9H2O were dissolved in 200 mL of deionized water and stirred for 2 h at room temperature. Then, 25 wt% ammonia solution was added dropwise to the solution to adjust the pH to approximately 10.5, and the mixture was stirred overnight at room temperature. The solid was collected by centrifugation, washed several times with water and ethanol, and then vacuum dried overnight at 50 °C. The dried solid was placed in a tube furnace and calcined at 500 °C for 4 h under an argon atmosphere at a heating rate of 5 °C / min. After cooling to room temperature, the catalyst MgAlO was obtained. x , marked as catalyst 9.

[0065] Catalytic performance of different catalysts, such as Figure 4 As shown:

[0066] (1) Effect of potassium precursor dosage on catalyst performance

[0067] Potassium was introduced to MgAlO x To create stronger basic sites on the basis of basicity. By changing the amount of potassium precursor during catalyst preparation, the conversion rate and selectivity of the reaction are reduced. Under standard conditions, it may reach the monolayer dispersion threshold, with the highest basic site density; when the amount of precursor is small, K + Highly dispersed, they bond with oxygen vacancies or defect sites on the support surface to form strong Lewis base sites, at which point the basicity of the catalyst is relatively insufficient; when the amount of potassium precursor is large, K species agglomerate to form K2CO3 or KOH nanoparticles, which are themselves weakly basic and easily block the pores of the support.

[0068] (2) Effect of magnesium-aluminum ratio on catalyst performance

[0069] The magnesium-aluminum ratio is crucial for constructing hydrotalcite-derived composite oxides (MgAlO). xThe core of the reaction is the support structure and alkalinity. Changing the magnesium-aluminum ratio during catalyst preparation yields different magnesium-aluminum hydrotalcite supports, all of which affect the reaction. Under standard conditions, a well-defined hydrotalcite precursor is formed, which, after calcination, yields highly dispersed MgAlO4 with a high specific surface area. x An ideal Mg / Al ratio creates the largest number of moderately strong basic sites, effectively activating reactants, promoting target condensation, and suppressing side reactions. As the magnesium / alkalinity increases, the number of strong basic sites increases. Numerous intrinsic strong basic sites appear in MgO, but their distribution is uneven. Potassium species tend to aggregate on the MgO surface. Excessively strong basic sites may lead to side reactions such as hydantoin ring-opening, acetone self-condensation, or further reactions of the target product, thus reducing selectivity. Furthermore, we found that magnesium-aluminum layered double hydroxides without potassium loading exhibit poor catalytic performance for this tandem reaction. The introduction of potassium enhances the basicity of the catalyst, enabling more efficient catalysis of condensation and hydrolysis reactions.

[0070] (3) Effect of different potassium salts on catalyst performance

[0071] Different potassium salts exhibit varying decomposition temperatures and gaseous products during calcination, potentially leading to differences in the surface properties of the support. We found that potassium nitrate precursors were superior to potassium carbonate precursors, possibly because potassium nitrate decomposes at a lower temperature, resulting in more complete decomposition, less residue, and easier formation of highly dispersed K active sites; while potassium carbonate decomposes at a much higher temperature (>900℃). At conventional calcination temperatures, it decomposes incompletely, existing instead as K₂CO₃ microcrystals on the support surface.

[0072] (4) Effect of different precipitants on catalyst performance

[0073] Precipitators affect the crystallinity, grain size, and compositional uniformity of the precursor hydrotalcite, thus influencing the texture and chemical properties of the final catalyst. Using ammonia as a precipitant results in more uniform precipitation, yielding a hydrotalcite precursor with smaller grains and a larger specific surface area, leading to better catalytic reaction. However, using urea as a precipitant may result in excessively slow precipitation, affecting the K+ content. + The distribution of basic sites is uneven. However, when sodium hydroxide is used as a precipitant, the precipitation rate may be too fast, leading to disordered support structure and uneven distribution of basic sites, including both strong and weak basic sites, resulting in a chaotic reaction pathway and poor selectivity. The specific surface area is also lower after calcination.

[0074] Example 3

[0075] Add 100g hydantoin, 70g acetone, 5g catalyst 1, and 300g water to a reaction flask, heat to 80℃, and react for 8 hours. After the reaction is complete, cool to room temperature, add 60g sodium hydroxide, and continue to heat to 100℃ for another 8 hours. After the reaction is complete, cool to room temperature, filter and collect the solution. HPLC calculation shows that the conversion rate of hydantoin is 80%, and the selectivity of ketovaline sodium is 92%.

[0076] This embodiment mainly examines the effect of sodium hydroxide as a co-catalyst on the reaction: Compared with Example 1, sodium hydroxide was not added as a co-catalyst in the first step of the condensation reaction. It can be seen that the catalyst conversion rate has decreased. This shows that sodium hydroxide can synergistically catalyze the condensation and hydrolysis reactions with a single-atom solid base catalyst.

[0077] Example 4

[0078] Add 100g hydantoin, 70g acetone, 10g sodium hydroxide, and 300g water to a reaction flask, heat to 80℃, and react for 8 hours. After the reaction is complete, cool to room temperature, add 50g sodium hydroxide, and continue to heat to 100℃ for another 8 hours. After the reaction is complete, cool to room temperature, filter and collect the solution. HPLC calculation shows that the conversion rate of hydantoin is 10%, and the selectivity of ketovaline sodium is 43%.

[0079] This example mainly examines the effect of solid base catalyst on the reaction: compared with Example 1, no solid base catalyst was added, and only sodium hydroxide was added as a catalyst. The reaction conversion rate and selectivity decreased sharply, indicating that solid base catalyst can efficiently catalyze two-step reactions in series.

[0080] Example 5

[0081] Add 100g hydantoin, 70g acetone, 2g catalyst 1, 10g sodium hydroxide, and 300g water to a reaction flask, heat to 80℃, and react for 8 hours. After the reaction is complete, cool to room temperature, add 50g sodium hydroxide, and continue to heat to 100℃ for another 8 hours. After the reaction is complete, cool to room temperature, filter and collect the solution. HPLC calculation shows that the conversion rate of hydantoin is 68% and the selectivity of ketovaline sodium is 95%.

[0082] This embodiment mainly examines the effect of the amount of solid base catalyst on the reaction: Compared with Example 1, the amount of solid base catalyst is reduced. When the amount of single-atom solid base catalyst is reduced, we find that the conversion rate of the reaction is reduced. When the amount of catalyst is too low, the condensation reaction is slow and incomplete, which affects the final reaction yield.

[0083] Example 6

[0084] Add 100g hydantoin, 70g acetone, 8g catalyst 1, 10g sodium hydroxide, and 300g water to a reaction flask, heat to 80℃, and react for 8 hours. After the reaction is complete, cool to room temperature, add 50g sodium hydroxide, and continue to heat to 100℃ for another 8 hours. After the reaction is complete, cool to room temperature, filter and collect the solution. HPLC calculations show that the conversion rate of hydantoin is 96% and the selectivity of ketovaline sodium is 81%.

[0085] This embodiment mainly examines the effect of the amount of solid base catalyst on the reaction: Compared with Example 1, the amount of solid base catalyst was increased. When the amount of single-atom solid base catalyst was increased, we found that the conversion rate of the reaction did not increase significantly, but the selectivity decreased. When the amount of catalyst is too high, the intermediate or product may be degraded, resulting in a decrease in selectivity.

[0086] Example 7

[0087] Add 100g hydantoin, 70g acetone, 5g catalyst 1, 10g sodium hydroxide, and 300g (50%) ethanol aqueous solution to a reaction flask. Heat to 80℃ and react for 8 hours. After the reaction is complete, cool to room temperature, add 50g sodium hydroxide, and continue to heat to 100℃ for another 8 hours. After the reaction is complete, cool to room temperature, filter and collect the solution. HPLC calculation shows that the conversion rate of hydantoin is 93% and the selectivity of ketovaline sodium is 88%.

[0088] This embodiment mainly examines the effect of different solvents on the reaction: Compared with Example 1, the solvent system uses a 50% aqueous ethanol solution as the reaction solvent. We found that compared with pure water as the reaction solvent, the conversion rate and selectivity of the reaction did not change significantly. Considering the cost, it is more appropriate to choose pure water as the solvent.

[0089] Example 8

[0090] Add 100g hydantoin, 70g acetone, 5g catalyst 1, 10g sodium hydroxide, and 300g water to a reaction flask, heat to 100℃, and react for 8 hours. After the reaction is complete, cool to room temperature, add 50g sodium hydroxide, and continue to heat to 100℃ for another 8 hours. After the reaction is complete, cool to room temperature, filter and collect the solution. HPLC calculations show that the conversion rate of hydantoin is 96% and the selectivity of ketovaline sodium is 84%.

[0091] This example mainly examines the effect of reaction temperature on the reaction: Compared with Example 1, the condensation reaction temperature was increased to 100°C. When the temperature of the condensation reaction increased, we found that the conversion rate of hydantoin did not increase significantly, but the selectivity of the product decreased. This may be due to the increase in side reactions caused by the increase in temperature.

[0092] Example 9

[0093] Add 100g hydantoin, 70g acetone, 5g catalyst 1, 10g sodium hydroxide, and 300g water to a reaction flask, heat to 80℃, and react for 8 hours. After the reaction is complete, cool to room temperature, add 50g sodium hydroxide, and continue to heat to 120℃ for another 8 hours. After the reaction is complete, cool to room temperature, filter and collect the solution. HPLC calculations show that the conversion rate of hydantoin is 95% and the selectivity of ketovaline sodium is 83%.

[0094] This example mainly examines the effect of reaction temperature on the reaction: Compared with Example 1, the hydrolysis reaction temperature was increased to 120°C. When the hydrolysis reaction temperature increased, we found that the selectivity of sodium ketovaline decreased, which may be due to product decomposition or reduced catalyst activity at excessively high temperatures.

[0095] Example 10

[0096] Add 100g hydantoin, 70g acetone, 5g catalyst 1, 10g sodium hydroxide, and 300g water to a reaction flask, heat to 80℃, and react for 8 hours. After the reaction is complete, cool to room temperature, add 100g sodium hydroxide, and continue to heat to 100℃ for another 8 hours. After the reaction is complete, cool to room temperature, filter and collect the solution. HPLC calculations show that the conversion rate of hydantoin is 95% and the selectivity of ketovaline sodium is 91%.

[0097] This embodiment mainly examines the effect of sodium hydroxide dosage on the reaction: Compared with Example 1, the amount of sodium hydroxide added during hydrolysis is increased. When more sodium hydroxide is added during hydrolysis, we find that the effect on the hydrolysis reaction is small. The reason is that the solid base catalyst can also catalyze the hydrolysis reaction more efficiently, which greatly reduces the amount of sodium hydroxide required for hydrolysis.

[0098] Example 11

[0099] Add 100g hydantoin, 70g acetone, 5g catalyst 1, 10g sodium hydroxide, and 300g water to a reaction flask. Heat to 80℃ and react for 8 hours. After the reaction is complete, cool to room temperature, add 100g sodium hydroxide, and continue heating to 100℃ for another 8 hours. After the reaction is complete, cool to room temperature, centrifuge to recover the catalyst, wash the catalyst several times with ethanol and water, dry it, and repeat the reaction to examine the catalyst's reusability. The results are as follows: Figure 5 As shown.

[0100] This embodiment mainly examines the cycle performance of the solid base catalyst: by Figure 5 It can be seen that the catalyst still exhibits high activity after being reused 5 times. This indicates that the solid base catalyst K / MgAlO prepared in this invention... x It exhibits good reusability, and its catalytic performance remains strong even after five cycles.

Claims

1. A method for preparing sodium ketovaline, characterized in that: Includes the following steps: Using hydantoin and acetone as raw materials, and a solid base catalyst K / MgAlO4 x Using sodium hydroxide as the main catalyst and sodium hydroxide as the co-catalyst, a condensation reaction is carried out in the presence of a solvent. After the condensation reaction is completed, sodium hydroxide is added, and the hydrolysis reaction is continued under the catalysis of a solid base catalyst to prepare sodium ketovaline. The solid base catalyst K / MgAlO x In the formula: x = 1 to 1.5; The solid base catalyst K / MgAlO x The solid alkali catalyst K / MgAlO was prepared by dissolving magnesium, aluminum, and potassium salts separately in deionized water, adding a precipitant, adjusting the pH, stirring and aging, filtering, washing, and vacuum drying to obtain a solid, which was then calcined. After calcination, the solid was cooled to room temperature to obtain the solid alkali catalyst K / MgAlO. x ; The precipitant is either ammonia or urea.

2. The method for preparing sodium ketovaline according to claim 1, characterized in that: The condensation and hydrolysis reactions are performed using a one-pot process, with a solid alkali catalyst K / MgAlO4. x Under catalysis, hydantoin, acetone and sodium hydroxide first undergo a condensation reaction at a lower temperature. After the reaction is complete, the temperature is directly increased to carry out a hydrolysis reaction.

3. The method for preparing sodium ketovaline according to claim 1, characterized in that: The magnesium salt is magnesium nitrate, the aluminum salt is aluminum nitrate, and the potassium salt is either potassium nitrate or potassium carbonate. The molar ratio of the magnesium salt, aluminum salt, and potassium salt is Mg:Al:K = 1~5:1:0.025~0.

075.

4. The method for preparing sodium ketovaline according to claim 1, characterized in that: The calcination process involves calcining at 400-600℃ for 2-6 hours in an argon atmosphere.

5. The method for preparing sodium ketovaline according to claim 1, characterized in that: In the condensation reaction, the solid base catalyst K / MgAlO x The dosage of hydantoin is 1-10 wt%, and the dosage of sodium hydroxide co-catalyst is 5-10 wt%.

6. The method for preparing sodium ketovaline according to claim 1, characterized in that: The condensation reaction was carried out at a temperature of 80°C for 8 hours; the hydrolysis reaction was carried out at a temperature of 100°C for 8 hours.

7. The method for preparing sodium ketovaline according to claim 1, characterized in that: In the hydrolysis reaction, the mass ratio of sodium hydroxide to hydantoin is 1:1-2.

8. The method for preparing sodium ketovaline according to claim 1, characterized in that: The solid base catalyst K / MgAlO x It can be recycled: after the reaction is completed, cool to room temperature, centrifuge to recover the catalyst, wash the catalyst several times with ethanol and water, dry it, and then carry out the reaction again.

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