A preparation method of 3-alkoxy-4-hydroxymandelic acid

Abstract

The present invention provides a method for preparing 3-alkoxy-4-hydroxymandelic acid, which comprises: in the presence of a catalyst and an auxiliary agent, o-alkoxyphenol and glyoxylic acid are subjected to a condensation reaction under alkaline conditions to obtain 3-alkoxy-4-hydroxymandelic acid; the catalyst is a tetraphenylporphyrin complex, and the auxiliary agent is a crown ether compound. The method has the advantages of high conversion rate, high selectivity for para-products, few by-products of glyoxylic acid disproportionation reaction, simple process, etc.

Description

Technical Field

[0001] The invention belongs to the technical field of condensation reaction of glyoxylic acid and phenols, and particularly relates to a method for preparing 3-alkoxy-4-hydroxymandelic acid. Background Art

[0002] Vanillin, chemically known as 3-methoxy-4-hydroxybenzaldehyde, is a white to slightly yellow needle-shaped crystal or crystalline powder with a unique aroma of vanilla beans. It is an important spice and food additive, and is widely used in the flavoring process of various foods and daily chemical products. The glyoxylic acid method is currently the most commonly used method for synthesizing vanillin. Compared with the traditional nitrosylation method, it has the characteristics of relatively low cost and easy treatment of three wastes. The vanillin obtained by this production method accounts for more than 80% of the global vanillin market. 3-Methoxy-4-hydroxymandelic acid is an important intermediate in the glyoxylic acid method. After oxidation and decarboxylation, the intermediate is obtained to obtain the vanillin product.

[0003] The reaction process of the glyoxylic acid method is as follows:

[0004]

[0005] At present, some reports on the glyoxylic acid process have been published:

[0006] CN101012161A uses methyl or ethyl guaiacol as raw materials and quaternary ammonium salt compounds as catalysts to prepare 3-methoxy (ethoxy)-4-hydroxymandelic acid. The reaction is improved in selectivity and yield by adding a catalyst and changing the feeding method, but the product yield is no more than 87%;

[0007] CN1320111A uses a diacid compound as a catalyst, and the reaction yield is also around 70-80%, with a large amount of ortho- and di-substituted byproducts in the product;

[0008] CN102086151A uses low temperature to prepare sodium glyoxylate and nitrogen atmosphere to prepare sodium guaiacol during the reaction process, and simultaneously accurately controls the temperature and pH, thereby increasing the reaction yield to more than 95%. However, under these conditions, the reaction time is relatively long, which greatly reduces the reaction efficiency.

[0009] CN109956858A uses a catalyst system in which a Salen complex is used as the main catalyst and an organic base containing a cation is used as the co-catalyst. The glyoxylic acid conversion rate and the main product selectivity are improved, and the yield can reach up to about 95%. However, the catalytic system is relatively complex and difficult to prepare.

[0010] In summary, the current glyoxylic acid method still has problems such as low reaction selectivity, generation of a large number of ortho-position by-products and dicondensation by-products, and harsh reaction conditions. Summary of the invention

[0011] The object of the present invention is to provide a method for preparing 3-alkoxy-4-hydroxymandelic acid, which has the advantages of high conversion rate, high selectivity for para-position products, few by-products of glyoxylic acid disproportionation reaction, simple process and the like.

[0012] The technical solution adopted by the present invention is as follows:

[0013] A method for preparing 3-alkoxy-4-hydroxymandelic acid comprises: in the presence of a catalyst and an auxiliary agent, o-alkoxyphenol and glyoxylic acid are subjected to a condensation reaction under alkaline conditions to prepare 3-alkoxy-4-hydroxymandelic acid.

[0014] The structure of the o-alkoxyphenol of the present invention is:

[0015]

[0016] Wherein R is a saturated hydrocarbon group having 1 to 4 carbon atoms, preferably a methyl group or an ethyl group;

[0017] The glyoxylic acid structure is:

[0018]

[0019] The catalyst of the present invention is a tetraphenylporphyrin complex having the structure:

[0020]

[0021] Among them, tetraphenylporphyrin cobalt is preferred.

[0022] The auxiliary agent of the present invention is a crown ether compound, including one or more of 12-crown-4, 15-crown-5 and 18-crown-6, among which 15-crown-5 is preferred.

[0023] The alkali of the present invention is one or more of sodium hydroxide, potassium hydroxide and lithium hydroxide, wherein sodium hydroxide is preferred.

[0024] The molar ratio of glyoxylic acid to o-alkoxyphenol of the present invention is 1:1-1.25, preferably 1:1.05-1.15; the molar ratio of glyoxylic acid to catalyst is 1:0.003-0.020, preferably 1:0.008-0.012; the molar ratio of glyoxylic acid to auxiliary agent is 1:0.0003-0.0020, preferably 0.0008-0.0012.

[0025] In a specific embodiment, the condensation reaction method of the present invention is: o-alkoxyphenol and alkali are mixed in water, which is recorded as solution A, and glyoxylic acid and alkali are mixed in water, which is recorded as solution B. Solution A, catalyst, and auxiliary agent are mixed to form a base, and solution B is added dropwise to the base solution at a certain temperature. After the addition is completed, the reaction is continued to obtain a product;

[0026] Wherein, the initial mass concentration of o-alkoxyphenol in the solution A is 10-30%, preferably 20-25%, and the molar ratio of o-alkoxyphenol to alkali is 1:1.0-1.15, preferably 1:1.0-1.05. The initial mass concentration of glyoxylic acid in the solution B is 10-40%, preferably 20-30%, and the molar ratio of glyoxylic acid to alkali is 1:1.0-1.2, preferably 1:1.0-1.05;

[0027] The temperature for dropping solution B into solution A is 25-35°C, preferably 28-32°C, and the dropping time is 1-3h, preferably 1.5-2.5h. After the dropping is completed, the reaction is continued for 3-6h, preferably 4-5h, and the continued reaction temperature is consistent with the dropping temperature.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] (1) Transition metal complex catalysts can activate glyoxylic acid and improve the conversion rate of glyoxylic acid. At the same time, the steric hindrance effect of the complex itself is used to reduce the possibility of glyoxylic acid attacking the ortho position of the phenolic hydroxyl group, thereby reducing the generation of ortho and disubstituted by-products;

[0030] (2) The presence of the auxiliary crown ether can interact with the cation, protect the adjacent active sites by increasing the ionic radius, and further reduce the formation of by-products.

[0031] (3) The presence of the auxiliary crown ether can also prevent the disproportionation reaction of glyoxylic acid under alkaline conditions and improve substrate selectivity.

[0032] The technical solution has a glyoxylic acid conversion rate greater than 99.5%, and a product selectivity not less than 95%. DETAILED DESCRIPTION

[0033] The present invention is further described below by means of specific examples. The examples described in the present invention are only used to illustrate the present invention and do not limit the scope of the present invention.

[0034] 1. Analysis and experimental methods:

[0035] The liquid chromatography reaction test conditions of the present invention are as follows: chromatographic model: Agilent 1260; chromatographic column: phenyl column; mobile phase: A: acetonitrile, B: 0.1% phosphoric acid aqueous solution; column temperature: 40°C; flow rate: 1.0mL / min; injection volume: 10μL; detection wavelength: 324nm.

[0036] (II) Sources of raw materials and reagents in various embodiments of the present invention:

[0037] Unless otherwise specified, all raw materials and reagents were purchased from commercial sources.

[0038] [Example 1]

[0039] 136.55g of o-methoxyphenol (1.1mol) and 44g of sodium hydroxide were mixed and dissolved in water, and the mass fraction of o-methoxyphenol was 20%. 6.72g of tetraphenylporphyrin cobalt and 0.22g of 15-crown-5 were added thereto, and the mixture was kept warm to 30°C as a base solution. 185.1g of 40% glyoxylic acid aqueous solution (1mol) and 40g of sodium hydroxide were mixed, and diluted with water to a glyoxylic acid mass fraction of 20%. The mixed solution was added dropwise to the base solution within 2h. After the addition was completed, the reaction was continued at 30°C for 4h. The glyoxylic acid conversion rate was tested to be 99.8%, and the selectivity was 96.7%.

[0040] [Example 2]

[0041] 145.8g o-ethoxyphenol (1.05mol) and 27.66g lithium hydroxide were mixed and dissolved in water, and the mass fraction of o-ethoxyphenol was 30%. 10.17g tetraphenylporphyrin zinc and 0.26g 12-crown-4 were added thereto, and the mixture was kept warm to 25°C as a base solution. 370.2g 20% ​​glyoxylic acid aqueous solution (1mol) and 25.15g lithium hydroxide were mixed, diluted with water to a glyoxylic acid mass fraction of 10%, and the mixed solution was added dropwise to the base solution within 1 hour. After the addition was completed, the reaction was continued at 25°C for 6 hours, and the glyoxylic acid conversion rate was tested to be 99.5%, and the selectivity was 95.1%.

[0042] [Example 3]

[0043] 182.63g of o-propoxyphenol (1.2mol) and 70.7g of potassium hydroxide were mixed and dissolved in water, and the mass fraction of o-propoxyphenol was 10%. 3.52g of tetraphenylporphyrin ferric chloride and 0.13g of 18-crown-6 were added thereto, and the mixture was kept warm to 35°C as a base solution. 105.77g of 70% glyoxylic acid aqueous solution (1mol) and 61.72g of potassium hydroxide were mixed, diluted with water to a glyoxylic acid mass fraction of 40%, and the mixed solution was added dropwise to the base solution within 3h. After the addition was completed, the reaction was continued at 35°C for 3h, and the glyoxylic acid conversion rate was tested to be 99.7%, and the selectivity was 96.1%.

[0044] [Comparative Example 1]

[0045] The preparation method of reference example 1 is different only in that no catalyst is used. After the reaction is completed, the glyoxylic acid conversion rate is 80.5% and the selectivity is 77.1%.

[0046] [Comparative Example 2]

[0047] The preparation method of reference example 1 is different only in that no auxiliary agent is used. After the reaction is completed, the glyoxylic acid conversion rate is 97.6% and the selectivity is 90.1%.

Claims

1. A method for preparing 3-alkoxy-4-hydroxymandelic acid, the method comprising: In the presence of a catalyst and an auxiliary agent, o-alkoxyphenol and glyoxylic acid undergo a condensation reaction under alkaline conditions to prepare 3-alkoxy-4-hydroxymandelic acid; Wherein, the catalyst is a tetraphenylporphyrin complex, and the structure is: The auxiliary agent is one or more of 12-crown-4, 15-crown-5 and 18-crown-6.

2. The method according to claim 1, characterized in that: The method comprises: mixing o-alkoxyphenol and alkali in water, which is referred to as solution A; Glyoxylic acid and alkali are mixed in water and recorded as solution B; Solution A, catalyst and auxiliary agent are mixed and laid as a base, and solution B is slowly added to the base liquid at a certain temperature. After the addition is completed, the reaction is continued to obtain the product.

3. The method according to claim 1 or 2, characterized in that: The structure of the o-alkoxyphenol is: Wherein R is a saturated hydrocarbon group having 1 to 4 carbon atoms.

4. The method according to claim 3, characterized in that: The molar ratio of glyoxylic acid to o-alkoxyphenol is 1:1-1.

25.

5. The method according to any one of claims 1 to 2, characterized in that: The molar ratio of glyoxylic acid to the catalyst is 1:0.003-0.

02.

6. The method according to any one of claims 1-2, characterized in that: The molar ratio of glyoxylic acid to the auxiliary agent is 1:0.0003-0.

002.

7. The method according to any one of claims 1-2, characterized in that: The alkali is one or more of sodium hydroxide, potassium hydroxide and lithium hydroxide.

8. The method according to claim 2, characterized in that: In solution A, the molar ratio of o-alkoxyphenol to base is 1:1.0-1.

15.

9. The method according to claim 2, characterized in that: In solution B, the molar ratio of glyoxylic acid to alkali is 1:1.0-1.

2.

10. The method according to claim 2, characterized in that The certain temperature is 25-35°C.

11. The method according to claim 2, characterized in that After solution B is added to the base solution, the reaction is continued for 3-6 hours.

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