A catalyst, a method for preparing the same, and use thereof

Abstract

The present application relates to a method for improving the yield of o-vanillin, and provides a novel metal ligand catalyst with the following structural formula: wherein M represents a transition metal such as iron, manganese, copper or chromium, and R represents H or methyl. The catalyst is introduced into a condensation reaction, which can greatly improve the ortho selectivity of mandelic acid, and further improve the yield of o-vanillin.

Description

Technical Field

[0001] This invention belongs to the field of catalysts, specifically relating to a novel ligand catalyst and its preparation method, and its application in the condensation reaction of glyoxylic acid and guaiacol to further improve the yield of o-vanillin. Background Technology

[0002] Vanillin and o-vanillin are important chemical products, used as intermediates in pharmaceuticals and fine chemicals. Vanillin is currently the world's largest-volume flavoring agent, possessing a rich milky aroma and widely used in food and daily chemical industries for flavoring and fixing. Chemical methods are the primary means of obtaining vanillin. o-Vanillin is a commonly used organic synthesis intermediate, used to synthesize 1,2,3-trimethoxybenzene, 1,2,3-trimethoxybenzene, brominated o-piperanal, phenolic epoxy resins, and 2,3-dimethoxybenzaldehyde, among others. O-Vanillin is also an important raw material for the production of berberine. Industrial-scale synthesis of o-Vanillin has not been reported; it is only obtained as a byproduct of vanillin production through purification and separation. Global vanillin production is approximately 20,000-30,000 tons per year, while o-Vanillin production is only in the hundreds of tons annually. O-Vanillin is more expensive than vanillin, making improving the yield of o-Vanillin crucial for enhancing the competitiveness of vanillin projects.

[0003]

[0004] As can be seen from the above synthetic equations, the synthetic routes of vanillin and o-vanillin are basically the same. Both use guaiacol and glyoxylic acid as raw materials, and proceed through three steps of condensation, oxidation, and decarboxylation to obtain vanillin and o-vanillin, respectively. The main difference between the two lies in the first step of the condensation reaction. If the condensation product is an o-hydroxymandelic acid derivative (1-hydroxy-2-methoxymandelic acid), the final product is o-vanillin; if the condensation product is p-hydroxymandelic acid (3-methoxy-4-hydroxymandelic acid), the final product is vanillin. Therefore, to improve the yield of vanillin, it is necessary to first improve the yield of o-hydroxymandelic acid generated in the first step of the reaction.

[0005] US Patent 535489 synthesizes o-hydroxymandelic acid from phenol and glyoxylic acid using a synergistic catalyst of metal salt and organic base, achieving high selectivity for o-hydroxymandelic acid. However, this process is a batch reaction, resulting in high catalyst consumption and production costs. Patent CN 1119312C discloses an industrial method for preparing sodium o-hydroxymandelic acid. Under the action of a tertiary amine and a trivalent metal cation catalyst, at a temperature below 100°C, and in an inert atmosphere, a condensation reaction of phenol and dihydroxyacetic acid solutions is carried out in two continuous reactors, achieving a selectivity of approximately 84% for o-hydroxymandelic acid. However, this process is only applicable to o-hydroxymandelic acid and not to 1-hydroxy-2-methoxymandelic acid. Patent CN102516045A discloses a method for preparing a mixture of o-vanillin and vanillin, using guaiacol and chloroform as raw materials, methanol as a medium, and proceeding with the addition of sodium hydroxide solution. The resulting product is pH adjusted to acidic to obtain a mixture of o-vanillin and vanillin. However, the overall yield of this process is low, making it an outdated process for vanillin synthesis. Summary of the Invention

[0006] To improve the selectivity of 1-hydroxy-2-methoxymandelic acid in the condensation reaction product and further increase the proportion of o-vanillin in the final product, this invention synthesizes a novel metal ligand catalyst with the following structural formula:

[0007]

[0008] M represents a transition metal, such as iron, manganese, copper, chromium, etc., and R represents H or methyl.

[0009] On the other hand, the present invention also provides a method for preparing the above-mentioned catalyst, comprising the following steps:

[0010] (1) 2-Bromoquinoline reacts with 2-(trimethyltin chloride)quinoline to give the biquinoline derivative shown in compound 1;

[0011] (2) The compound 1 obtained in step (1) was reacted with concentrated sulfuric acid to obtain the sulfonated derivative shown in compound 2;

[0012] (3) The compound 2 obtained in step (2) is mixed and stirred with transition metal ions to obtain a metal ligand catalyst;

[0013] The structural formula of 2-(trimethylstannous chloride)quinoline is: Compound 1 is Compound 2 is

[0014] The following diagram illustrates the synthesis of this compound:

[0015]

[0016] The step (1) described in this invention is carried out under anhydrous and oxygen-free conditions.

[0017] Step (1) of the present invention can be carried out in solvent A, wherein solvent A is selected from one or more of toluene, diethyl ether, and tetrahydrofuran, preferably toluene and diethyl ether.

[0018] In step (1) of the present invention, the weight ratio of 2-bromoquinoline to solvent A is 1:(3-10), preferably 1:(5-8).

[0019] In step (1) of the present invention, the mass ratio of 2-bromoquinoline to 2-(trimethyltin chloride)quinoline is 1:(0.8-2.5), preferably 1:(1.2-1.8).

[0020] In step (1) of this invention, the synthesis method of 2-(trimethyltin chloride)quinoline is as follows: under anhydrous and oxygen-free conditions, at 0-5°C, trimethyltin chloride and quinoline are reacted to obtain the product.

[0021] In step (1) of the present invention, the reaction temperature is 0-50℃, and the preferred reaction temperature is 10-30℃.

[0022] In step (1) of the present invention, the reaction time is 1-12h, and the preferred reaction temperature is 3-6h.

[0023] In step (2) of this invention, the concentrated sulfuric acid is fuming sulfuric acid or 98wt% concentrated sulfuric acid.

[0024] The reaction conditions for step (2) of this invention are normal temperature and pressure.

[0025] The reaction time for step (2) of the present invention is 1 to 8 hours, preferably 3 to 5 hours.

[0026] Step (2) of the present invention is carried out in solvent B, wherein solvent B is selected from one or more of acetone, DMF, ethanol and methanol, preferably acetone or ethanol.

[0027] In step (2) of the present invention, the mass ratio of compound 1 to solvent B is 1:(3-10), preferably 1:(5-8).

[0028] In step (2) of the present invention, the mass ratio of sulfuric acid to compound 1 is (0.5-5):1, preferably (2-4):1.

[0029] In step (3) of the present invention, the metal ions are selected from aqueous solutions of ferric chloride, ferric nitrate, ferric sulfate, copper chloride, copper sulfate, copper nitrate, cobalt chloride, cobalt sulfate, and cobalt nitrate. The preferred sources of metal ions are ferric sulfate and cobalt sulfate solutions.

[0030] In step (3) of this invention, the concentration of the metal ion solution is 5-15 wt%.

[0031] In step (3) of the present invention, the mass ratio of the metal ion solution to compound 2 is (5-20):1, preferably (10-15):1.

[0032] The reaction temperature in step (3) of the present invention is 10-60°C, preferably 30-50°C.

[0033] The reaction time for step (3) of the present invention is 0.1 to 3 hours, preferably 0.5 to 1.5 hours.

[0034] On the other hand, the present invention also provides a method for preparing o-vanillin, the method comprising: condensing guaiacol and glyoxylic acid in a mass ratio of catalyst:guaiacol:glyoxylic acid of (0.001-0.01):(0.8-1.2):1, wherein the reaction temperature is 20-40℃, the reaction pressure is atmospheric pressure, the pH of the reaction solution is 12-13, and the reaction time is 2-8h.

[0035] The condensed reaction solution was subjected to oxidation, decarboxylation, and purification to obtain o-vanillin and vanillin products. Specifically, sulfuric acid was added to adjust the pH of the condensed reaction solution to 4-5, and toluene was added for extraction to recover guaiacol, with a toluene-to-water mass ratio of 1:(3-5). The reaction solution was then adjusted to alkalinity, controlling the pH at 12-13, and reacted with 10%-20% copper oxide at atmospheric pressure and 100℃ for 4-8 hours to obtain an oxidation reaction solution containing 3-methoxy-4-hydroxyphenylacetic acid. After filtering to separate the copper oxide, 3-5% sulfuric acid was added to induce a decarboxylation reaction to obtain crude vanillin. The crude vanillin was further purified by distillation on approximately 20-25 plates to obtain pure o-vanillin and vanillin.

[0036] The above is an illustrative preparation scheme for o-vanillin. For specific methods, please refer to patent CN102010310A.

[0037] The beneficial effects of this invention are as follows:

[0038] A novel metal ion ligand catalyst was synthesized using the method of this invention and applied to the condensation reaction of guaiacol and glyoxylic acid to produce mandelic acid. The biquinoline ligand possesses a large specific surface area and steric hindrance. The large specific surface area promotes the dispersion of the bound metal ions, allowing for a larger contact area with the reactants. Furthermore, the biquinoline has a suitable conjugated structure and certain acidic activation sites, which inhibit para-selectivity, thereby improving ortho-product selectivity. Introducing a sulfonic acid group onto the ligand makes the catalyst water-soluble. This homogeneous reaction significantly improves the reactivity and avoids the problem of catalyst separation. Transition metal ions can enhance the reactivity of the condensation reaction. The metal ligand catalyst obtained by combining with biquinoline can significantly increase the yield of 1-hydroxy-2-methoxymandelic acid in the condensation reaction. Further oxidation, decarboxylation, and purification processes can further increase the proportion of ortho-vanillin in the final product. Detailed Implementation

[0039] The following embodiments will further illustrate the method provided by the present invention, but the present invention is not limited to the listed embodiments, and should also include any other known modifications within the scope of the claims of the present invention.

[0040] Raw materials and their sources;

[0041] 2-Bromoquinoline 98% Bailingwei Technology Co., Ltd.

[0042] Toluene 99% Sinopharm Group Co., Ltd.

[0043] 98% concentrated sulfuric acid, Sinopharm Group Co., Ltd.

[0044] Copper sulfate 99.5% Beijing Inokai Technology Co., Ltd.

[0045] Guaiac 99% Aladdin Technology Co., Ltd.

[0046] 50% Glyoxylic Acid Aladdin Technology Co., Ltd.

[0047] Test method: The contents of glyoxylic acid, o- / p-mandelic acid and guaiacol in the system were determined by Agilent liquid chromatography using the external standard method. The mobile phase of liquid chromatography was acetonitrile and aqueous phosphoric acid solution. A benzene-based column was used, with a column temperature of 40-45℃ and a detector of 230nm-250nm.

[0048] Synthesis of 2-(trimethyltin chloride)quinoline: Trimethyltin chloride and quinoline were reacted at 5°C in an anhydrous and oxygen-free environment for 10 h at a molar ratio of 1:1 to obtain the product.

[0049] Example 1

[0050] Under anhydrous and oxygen-free conditions at 20°C, 40 g of 2-bromoquinoline and 200 g of toluene were injected into a three-necked flask. 40 g of 2-(trimethylstannous chloride)quinoline was then slowly added dropwise to the reaction system. After the addition was complete, the reaction continued for 3 hours. The reaction was quenched with water, and the upper oil phase was separated by rotary evaporation and then subjected to column chromatography. The eluent was petroleum ether and ethyl acetate in a 3:1 ratio. Compound 1 was obtained after separation and purification. At room temperature and pressure, 60 g of compound 1 was dissolved in 300 g of toluene. 120 g of 98% concentrated sulfuric acid was added dropwise to the reaction solution, and the reaction continued for 4 hours. After the reaction was completed, the toluene was removed from the reaction solution, and the solution was recrystallized from ethanol and water (1:8) at a solvent-to-crude product mass ratio of 4:1. The recrystallization temperature was controlled at 17°C to obtain compound 2. Mix 80g of compound 2 with 800g of copper sulfate solution (10%), stir at 40℃ for 1h, and wait for flocculent solid to precipitate. Filter and wash to obtain the metal ligand catalyst. Apply this catalyst to a condensation reaction, where the mass ratio of catalyst:guaiacol:glyoxylic acid = 0.005:1.05:1, the reaction temperature is 30℃, the pH of the reaction solution is 12.7, and the reaction time is 5h. The selectivity for 1-hydroxy-2-methoxymandelic acid (ortho-mandelic acid) is approximately 75.2%, and the selectivity for 3-methoxy-4-hydroxymandelic acid (para-mandelic acid) is approximately 18.78%. Adjust the pH of the condensation reaction solution to 4.2 with sulfuric acid, add toluene to extract and recover guaiacol, and the mass ratio of toluene to aqueous phase is 1:3. The reaction solution was then adjusted to alkalinity, with pH controlled at 12.5. It was reacted with 15% copper oxide at atmospheric pressure and 100°C for 6 hours to obtain an oxidation reaction solution containing 3-methoxy-4-hydroxyphenyl benzoic acid. After filtering to separate the copper oxide, 4% sulfuric acid was added to induce a decarboxylation reaction, yielding crude vanillin. The crude vanillin was further distilled using approximately 20 distillation plates to obtain pure o-vanillin and vanillin, with a mass ratio of o-vanillin to vanillin of 4.15.

[0051] Example 2

[0052] Under anhydrous and oxygen-free conditions at 5°C, 40 g of 2-bromoquinoline and 140 g of diethyl ether were injected into a three-necked flask. 88 g of 2-(trimethyltin chloride)-3-methylquinoline was slowly added dropwise to the reaction system. After the addition was complete, the reaction continued for 1.5 h. The reaction was then quenched with water. The upper oil phase was separated by rotary evaporation and then subjected to column chromatography. The eluent was petroleum ether and ethyl acetate in a 3:1 ratio. Compound 1 was obtained after separation and purification. At room temperature and pressure, 60 g of compound 1 was dissolved in 240 g of DMF. 36 g of fuming sulfuric acid was added dropwise to the reaction solution, and the reaction continued for 2 h. After the reaction was completed, the solvent was removed from the reaction solution, and recrystallization was performed using a 1:8 solution of ethanol and water (solvent to crude product mass ratio of 4:1) at 16°C to obtain compound 2. 80g of compound 2 and 480g of ferric chloride solution (6%) were mixed and stirred at 20℃ for 0.2h. After flocculent solids precipitated, the mixture was filtered and washed to obtain the metal ligand catalyst. This catalyst was applied to a condensation reaction with a catalyst:guaiacol:glyoxylic acid mass ratio of 0.002:0.85:1, a reaction temperature of 25℃, a reaction solution pH of 12.2, and a reaction time of 3h. The selectivity for 1-hydroxy-2-methoxymandelic acid (ortho-mandelic acid) was approximately 68.4%, and the selectivity for 3-methoxy-4-hydroxymandelic acid (para-mandelic acid) was approximately 22.76%. The condensed reaction solution was adjusted to pH 4.5 with sulfuric acid, and guaiacol was extracted with toluene at a toluene:water mass ratio of 1:3. The reaction solution was then adjusted to alkalinity, with pH controlled at 12.3. It was reacted with 16% copper oxide at atmospheric pressure and 100°C for 4.5 hours to obtain an oxidation reaction solution containing 3-methoxy-4-hydroxyphenyl benzoic acid. After filtering to separate the copper oxide, 3.7% sulfuric acid was added to induce a decarboxylation reaction, yielding crude vanillin. The crude vanillin was further distilled using approximately 22 distillation plates to obtain pure o-vanillin and vanillin, with a mass ratio of o-vanillin to vanillin of 3.02.

[0053] Example 3

[0054] Under anhydrous and oxygen-free conditions at 45°C, 40 g of 2-bromoquinoline and 360 g of tetrahydrofuran were injected into a three-necked flask. 34 g of 2-(trimethylstannous chloride)quinoline was then slowly added dropwise to the reaction system. After the addition was complete, the reaction continued for 11 hours. The reaction was quenched with water, and the upper oil phase was separated by rotary evaporation and then subjected to column chromatography. The eluent was petroleum ether and ethyl acetate in a 3:1 ratio. Compound 1 was obtained after separation and purification. At room temperature and pressure, 60 g of compound 1 was dissolved in 540 g of ethanol, and 270 g of 98% sulfuric acid was added dropwise to the reaction solution. The reaction continued for 7 hours. After the reaction was completed, the solvent was removed from the reaction solution, and recrystallization was performed using an ethanol and water (1:8) solution with a solvent-to-crude product mass ratio of 4:1 at 18°C ​​to obtain compound 2. 80g of compound 2 and 1440g of cobalt sulfate solution (14%) were mixed and stirred at 55℃ for 2.8h. After flocculent solids precipitated, the mixture was filtered and washed to obtain the metal ligand catalyst. This catalyst was applied to a condensation reaction with a catalyst:guaiacol:glyoxylic acid mass ratio of 0.01:1.2:1, a reaction temperature of 38℃, a reaction solution pH of 12.9, and a reaction time of 7h. The selectivity for 1-hydroxy-2-methoxymandelic acid (ortho-mandelic acid) was approximately 72.5%, and the selectivity for 3-methoxy-4-hydroxymandelic acid (para-mandelic acid) was approximately 19.3%. The condensed reaction solution was adjusted to pH 4.8 with sulfuric acid, and guaiacol was extracted with toluene at a toluene:water mass ratio of 1:3. The reaction solution was then adjusted to alkalinity, with pH controlled at 12.7. It was then reacted with 17% copper oxide at atmospheric pressure and 100°C for 6.5 hours to obtain an oxidation reaction solution containing 3-methoxy-4-hydroxyphenyl benzoic acid. After filtering to separate the copper oxide, 4.4% sulfuric acid was added to induce a decarboxylation reaction, yielding crude vanillin. Further distillation of the crude vanillin, using approximately 25 distillation plates, yielded pure o-vanillin and pure vanillin. The mass ratio of o-vanillin to vanillin in the product was 3.75.

[0055] Example 4

[0056] Under anhydrous and oxygen-free conditions at 30°C, 40 g of 2-bromoquinoline and 240 g of toluene were injected into a three-necked flask. 60 g of 2-(trimethyltin chloride)quinoline was then slowly added dropwise to the reaction system. After the addition was complete, the reaction continued for 5 hours. The reaction was quenched with water, and the upper oil phase was separated by rotary evaporation and then subjected to column chromatography. The eluent was petroleum ether and ethyl acetate in a 3:1 ratio. Compound 1 was obtained after separation and purification. At room temperature and pressure, 60 g of compound 1 was dissolved in 360 g of methanol, and 180 g of fuming sulfuric acid was added dropwise to the reaction solution. The reaction continued for 3 hours. After the reaction was completed, the solvent was removed from the reaction solution, and recrystallization was performed using an ethanol and water (1:8) solution at a crystallization mass ratio of 4:1 and a crystallization temperature of 18°C ​​to obtain compound 2. 80 g of compound 2 was mixed with 960 g of copper chloride solution (8%) and stirred at 35°C for 1.2 hours. After flocculent solids precipitated, the solids were filtered and washed to obtain the metal ligand catalyst. The catalyst was applied to a condensation reaction with a catalyst:guaiacol:glyoxylic acid mass ratio of 0.003:1.1:1, a reaction temperature of 30℃, a reaction solution pH of 12.1, and a reaction time of 6 h. The selectivity for 1-hydroxy-2-methoxymandelic acid (ortho-mandelic acid) was approximately 60.8%, and the selectivity for 3-methoxy-4-hydroxymandelic acid (para-mandelic acid) was approximately 25.3%. The condensed reaction solution was adjusted to pH 5 with sulfuric acid, and guaiacol was extracted with toluene at a toluene:water mass ratio of 1:3. The reaction solution was then adjusted to alkalinity, with pH controlled at 12.5. It was then reacted with 20% copper oxide at atmospheric pressure and 100°C for 4-8 hours to obtain an oxidation reaction solution containing 3-methoxy-4-hydroxyphenyl benzoic acid. After filtering to separate the copper oxide, 5% sulfuric acid was added to induce a decarboxylation reaction, yielding crude vanillin. The crude vanillin was further distilled using approximately 20 distillation plates to obtain pure o-vanillin and vanillin. The mass ratio of o-vanillin to vanillin in the product was 2.59.

[0057] Comparative Example 1

[0058] The reaction was carried out with guaiacol:glyoxylic acid in a mass ratio of 1.05:1 at 30°C, pH 12.7, and a reaction time of 5 h. The selectivity for 1-hydroxy-2-methoxymandelic acid (ortho-mandelic acid) was approximately 33.2%, and the selectivity for 3-methoxy-4-hydroxymandelic acid (para-mandelic acid) was approximately 59.6%. The condensation reaction solution was adjusted to acidity, and methyl isobutyl ketone was added for extraction to recover unreacted guaiacol. The remaining aqueous phase was adjusted to pH 13 with alkali, and oxidation was continued at 85°C for 2 h. Then, sulfuric acid was added for decarboxylation. After decarboxylation, methyl isobutyl ketone was added to extract vanillin. The extract was then subjected to distillation and crystallization to obtain vanillin and ortho-vanillin, with an ortho-vanillin:vanillin mass ratio of 0.58.

Claims

1. A metal ligand catalyst, having the following structure: wherein M represents transition metal iron, cobalt, copper, and R represents H or methyl. comprising the following steps:

2. The method for preparing the metal ligand catalyst according to claim 1, characterized in that, (1) reacting 2-bromoquinoline with 2-(trimethyltin)quinoline to obtain a biquinoline derivative as shown in compound 1; the 2-(trimethyltin)quinoline is synthesized by the following method: under anhydrous and anaerobic conditions, trimethyltin chloride and quinoline are reacted at 5°C at a molar ratio of 1:1 for 10 h to obtain; (2) reacting the compound 1 obtained in step (1) with concentrated sulfuric acid to obtain a sulfonated derivative as shown in compound 2; (3) mixing and stirring the compound 2 obtained in step (2) with a transition metal ion to obtain a metal ligand catalyst; Step (1) is carried out in a solvent A selected from one or more of toluene, diethyl ether, and tetrahydrofuran; the weight ratio of 2-bromoquinoline to the solvent A is 1:(3-10); and the mass ratio of 2-bromoquinoline to 2-(trimethyltin)quinoline is 1:(0.8-2.5). wherein the structure of 2-(trimethyltin)quinoline is Compound 1 is Compound 2 is 3. The production method according to claim 2, wherein The reaction temperature in step (1) is 0-50°C; and the reaction time in step (1) is 1-12 h.

4. The production method according to claim 2, wherein The reaction time in step (2) is 1-8 h; and step (2) is carried out in a solvent B selected from one or more of acetone, DMF, ethanol, and methanol.

5. The production method according to any one of claims 2 to 4, wherein The mass ratio of compound 1 to the solvent B in step (2) is 1:(3-10); and the mass ratio of sulfuric acid to compound 1 in step (2) is (0.5-5):

1.

6. The production method according to any one of claims 2 to 4, wherein The metal ion in step (3) is selected from an aqueous solution of ferric chloride, ferric nitrate, ferric sulfate, cupric chloride, cupric sulfate, cupric nitrate, cobalt chloride, cobalt sulfate, and cobalt nitrate; the concentration of the metal ion solution in step (3) is 5-15 wt%; and the mass ratio of the metal ion solution to compound 2 in step (3) is (5-20):

1.

7. The production method according to any one of claims 2 to 4, wherein The reaction temperature in step (3) is 10-60°C; and the reaction time in step (3) is 0.1-3 h.

8. The production method according to any one of claims 2 to 4, wherein 9. A preparation method of o-vanillin, comprising: condensing guaiacol and glyoxylic acid at a catalyst: guaiacol: glyoxylic acid mass ratio of (0.001-0.01):(0.8-1.2):1, and subjecting the reaction liquid after the condensation to oxidation, decarboxylation, and refining to obtain o-vanillin and vanillin products; and the catalyst is selected from the metal ligand catalyst of claim 1 or the metal ligand catalyst prepared by the preparation method of any one of claims 2-8. ​ 10. The production method according to claim 9, wherein The condensation reaction temperature is 20-40℃, the reaction pressure is normal pressure, the reaction liquid pH is 12-13, and the reaction time is 2-8h; the oxidation, decarboxylation and refining process comprises the following steps: after condensation, the reaction liquid is adjusted to pH=4-5 with sulfuric acid, toluene is added for extraction to recover guaiacol, the mass ratio of toluene to water is 1:(3-5); then the reaction liquid is adjusted to alkaline, pH=12-13 is controlled, and 10%-20% copper oxide is added for reaction at normal pressure and 100℃ for 4-8h to obtain an oxidation reaction liquid containing 3-methoxy-4-hydroxyphenone acid; after filtration separation of copper oxide, 3-5% sulfuric acid is added for decarboxylation to obtain vanillin crude product; the vanillin crude product is further rectified, the number of rectification plates is 20-25, and pure ortho-vanillin and vanillin are obtained.

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