Preparation method of gallic acid and derivative thereof

Abstract

The invention relates to a preparation method of gallic acid and derivatives thereof, and belongs to the technical field of chemical products, the gallic acid and derivatives thereof comprise a compound 1, a compound 2, a compound 3 and a compound 4, the compound 3 adopts 3, 5-dihalogeno-4-hydroxybenzoic acid as a raw material and is hydrolyzed to obtain gallic acid, and the compound 4 adopts p-hydroxybenzoic acid as a raw material and is hydrolyzed to obtain the gallic acid. Gallic acid is obtained through secondary sulfonation and alkali fusion and acid precipitation, and gallic acid ester is obtained through esterification of gallic acid, ethyl alcohol and propyl alcohol. According to the preparation method of the gallic acid and the gallic acid derivative, 3, 5-dihalogenated-4-hydroxybenzoic acid is synthesized through halogenation, 3, 4, 5-trihydroxybenzoic acid is obtained through hydrolysis, and the process is simple and easy to implement; by adopting p-hydroxybenzoic acid as an initial raw material and adopting a traditional sulfonation alkali fusion method, the process is mature and stable, the reaction process is simple, the raw materials are easy to obtain, the product yield is relatively high, required equipment is conventional equipment, and industrial preparation is easy to realize.

Description

Technical Field

[0001] The invention relates to the technical field of chemical products, and in particular to a method for preparing gallic acid and its derivatives. Background Art

[0002] Gallic acid, white or light brown needle crystals or powder. Melting point 235-240℃ (decomposition). When heated to 100-120℃, it loses crystal water. When heated to above 200℃, it loses carbon dioxide to generate pyrogallol (i.e. pyrogallol). Gallic acid is widely used in food, feed, biology, medicine, chemical industry, electronic chemicals and other fields.

[0003] Gallic acid can be used as a raw material to synthesize gallic acid ester compounds. Alkyl esters of gallic acid can be divided into low-level esters (such as methyl ester, ethyl ester, propyl ester, etc.) and high-level esters (such as octyl ester, lauryl ester, octadecyl alcohol ester, etc.) according to the number of carbon atoms in the alkyl group. These ester compounds are excellent food antioxidants. Propyl gallate is an antioxidant that can be used in edible oils to prevent rancidity and deterioration. Propyl gallate (PG) has been approved for use in many countries.

[0004] Gallic acid can be used to make a variety of fuels, flame stabilizers, blue-black ink (gallic acid and trivalent iron ions generate blue-black precipitation, which is the raw material of blue-black ink) and flute agents. It is used with vitamin C as a reinforced bait for fish farming. Most aquatic products abroad use gallic acid as an antioxidant instead of dipping or spraying. It is an ultraviolet absorber, flame retardant, semiconductor photoresist raw material, can be used to prepare anti-rust primer and aluminum alloy organic coating, and fluidizer for water-based drilling mud. Its effect is comparable to that of lignin sulfonate, or even better. It is also used in leather making in industry; it can also be used as a photographic developer. It is also used as a developer and an analytical reagent for detecting free inorganic acids, dihydroxyacetone, alkaloids and metals. Gallic acid is a common plant growth regulator, widely used in agricultural preparation and horticultural planting, which can promote plant growth and development and improve yield and quality.

[0005] In addition, the triphenolic hydroxyl group on the benzene ring of gallic acid has high reactivity and can undergo etherification reaction with dialkyl sulfate, halogenated hydrocarbons, p-toluenesulfonyl esters, etc. under alkaline conditions. The generated etherification products such as 3,4,5-trimethoxybenzoic acid and 3,4,5-tribenzylbenzoic acid are important intermediates for the synthesis of antibacterial, anti-cardiovascular disease, anti-cancer and other drugs.

[0006] There are mainly three methods for preparing gallic acid in the prior art:

[0007] (1) The acid (base) hydrolysis method of tannic acid extracted from natural sources: mainly divided into one-step method and two-step method. The main process flow of the two-step method for preparing gallic acid: raw materials → hot water extraction → filter out the residue → concentrate the tannin aqueous solution to about 20% → add acid to hydrolyze → cool and crystallize → centrifuge to obtain the crude product → dissolve the crude product and add carbon to decolorize → filter and cool and crystallize → centrifuge → dry → gallic acid finished product.

[0008] (2) Microbial fermentation method: The fermentation method uses microorganisms to ferment in a tannin-containing aqueous solution, using the glucose in the tannin as a carbon source for the growth and reproduction of microorganisms. The biological enzymes produced by the induced microorganisms catalyze the hydrolysis of tannins. Process flow: grind the raw materials to a diameter of less than 10 mm → sieve out the insect powder → soak with water to a 30% tannin solution → add black mold strains → ferment for 8 to 9 days → filter → wash with water → crude gallic acid → dissolve and recrystallize → industrial gallic acid. The main problem with the fermentation method is that the formation of biological enzymes and the hydrolysis of tannins are carried out in the same reaction vessel, and the process conditions are difficult to reach the optimal state, resulting in a longer reaction cycle (more than 3 days), incomplete tannin hydrolysis, and residual tannins reaching 15% to 20%.

[0009] (3) Enzymatic method: In view of the defects of the fermentation method for preparing gallic acid, new enzymatic processes have been developed at home and abroad. The key to the enzymatic method is to screen and prepare efficient biological enzymes. Tanninase is an acetyl hydrolase, which is an acyl hydrolase induced outside the spores. It can efficiently, specifically and directionally cleave the ester bonds, phenol bonds and glycosidic bonds in the tannin molecules to generate gallic acid. Under appropriate conditions, a variety of molds can react with the inducer tannin to produce tanninase. The strain generally used is Aspergillus niger. Process flow: enzyme culture → fermentation enzyme production → (add raw materials) hydrolysis → filtration → concentration → crude crystallization → separation → decolorization → primary crystallization → secondary crystallization → drying → crushing → finished gallic acid. Compared with the fermentation method, the enzymatic method has a significantly shorter reaction time, the tannin hydrolysis conversion rate is over 98%, and the consumption index and preparation cost are significantly reduced.

[0010] The main raw material of the above three preparation processes is tannic acid in gallnut. China is the main producer of gallnut, accounting for about 95% of the world's total production. In China, gallnut is mainly concentrated in Guizhou, Sichuan, Hubei, Hunan, Shaanxi, Yunnan and other provinces. The above six provinces account for more than 90% of China's gallnut production.

[0011] The production capacity of natural raw material gallnut cannot fully meet the market demand. Therefore, it is imperative to develop a green, efficient and economical chemical synthesis preparation process. We have developed a preparation process for chemical synthesis of gallic acid (3,4,5-trihydroxybenzoic acid) and its derivatives. The preparation method has good product yield, good reaction selectivity, effectively controls the generation of impurities such as isomers, and has good product quality. Summary of the invention

[0012] In view of the deficiencies in the prior art, the present invention provides a method for preparing gallic acid and its derivatives, which has the advantages of good reaction selectivity and high product yield, effectively controls the generation of impurities such as isomers, and has good product quality.

[0013] To achieve the above object, the present invention provides the following technical solution: a method for preparing gallic acid, comprising compound 1, compound 2, compound 3 and compound 4, wherein the chemical structural formulas of compound 1, compound 2, compound 3 and compound 4 are as follows;

[0014]

[0015] In the formula: R1 is a hydroxyl group; R2 is a carboxyl group or an alkyl group; R3 and R4 are halogens (Cl, Br, I);

[0016] The compound 1 is hydrolyzed under certain conditions to obtain compound 3, and the chemical synthesis formula of compound 3 is:

[0017]

[0018] The compound 3 uses 3,5-dihalogenated-4-hydroxybenzoic acid as a raw material and is hydrolyzed to obtain gallic acid;

[0019] The compound 2 is subjected to secondary sulfonation and alkali fusion to obtain compound 4, and the chemical synthesis formula of compound 4 is:

[0020]

[0021] In the formula, the substituent R1 is a hydroxyl group, and the substituent R2 is any one of a carboxyl group or a C1-C18 alkyl group;

[0022] The compound 4 uses p-hydroxybenzoic acid as a raw material, and undergoes secondary sulfonation, alkali fusion and acid precipitation to obtain gallic acid;

[0023] The preparation method of compound 3 comprises the following steps:

[0024] A1. Add 3,5-dibromo-4-hydroxybenzoic acid into a solvent to prepare a 3,5-dibromo-4-hydroxybenzoic acid solution;

[0025] A2. According to a certain ratio, add liquid alkali into the reactor first, add phase transfer catalyst benzyltriethylammonium chloride, slowly add the prepared 3,5-dibromo-4-hydroxybenzoic acid solution, heat to 100-200 degrees, the pressure in the reactor is 0.4-1.5MPa, maintain for 3-6 hours, and continue stirring and keeping warm for 3 hours;

[0026] A3, cool down to 75-80 degrees, transfer the material to the acid hydrolysis kettle, add 30-40% sulfuric acid solution, after passing the test, cool down to 0 degrees; stir for 2 hours, filter to get the crude product;

[0027] A4. The crude product was transferred into the solvent system in the crystallization kettle, heated and dissolved, and then crystallized. The gallic acid product was filtered to obtain a yield of 80%;

[0028] The preparation method of compound 4 comprises the following steps:

[0029] B1. Add p-hydroxybenzoic acid, concentrated sulfuric acid and oleum in a molar ratio of 1:4.2:4.0 into a reactor, heat to 120-170°C, control the free acid at 1-3%, use concentrated sulfuric acid for monosulfonation, and use oleum for disulfonation, which is completed in about 10 hours or the sulfonation yield is 85%;

[0030] B2, the sulfonated liquid is treated with liquid alkali to obtain crude sodium sulfonate, which is filtered and precipitated for use; the neutralization yield is 98-99%;

[0031] B3, add the required molar amount of caustic soda flakes, when the temperature in the alkali melting kettle rises to 350 degrees, start stirring, start to slowly add sodium benzenesulfonate, keep the temperature in the reactor at 350-370 degrees, continue stirring for 3 hours; control the free alkali to 1-3%; pass water vapor into the upper part of the alkali melting kettle for protection to prevent side reactions such as oxidation and coking;

[0032] B4, put the material with good alkali fusion reaction into water with a volume 3 times that of the alkali fusion material, and clarify and separate it after dilution; the sodium phenolate solution is acidified; the solid sodium sulfite is filtered, washed, and vacuum filtered to obtain a sodium sulfite byproduct for sulfonation neutralization;

[0033] B5, control the vacuum degree to 26.67-53.33 kPa; when the sulfur dioxide produced in the neutralization section is sent to the acidification pot, the diluted sodium phenolate solution is continuously added to the acidification pot, and the reaction temperature is about 70°C; the reaction is controlled to be slightly acidic (pH=6-7); the crude phenol solution and the sodium sulfite solution are separated by clarification and separation; the crude phenol solution is extracted and purified, and the sodium sulfite solution is used for neutralization;

[0034] B6. When sulfuric acid cannot be used for sulfuric acid dioxide, sulfuric acid or hydrochloric acid can be used for acidification; 93% sulfuric acid is added evenly over 0.75-1h, the temperature is controlled at 60-75°C, and the end point control is the same as that for sulfuric acid dioxide; the acidification yield is 95-98%%;

[0035] B7. The crude 3,4,5-trihydroxybenzoic acid is extracted and purified 2-3 times with a mixed solvent of toluene + fatty alcohol to obtain a product; the product purity is ≥98.0%, and the total yield calculated based on p-hydroxybenzoic acid is 40-50%; the product in the mother liquor is reserved for subsequent treatment.

[0036] Furthermore, R3 and R4 are any one of halogen chlorine, halogen bromine or halogen iodine.

[0037] Further, when R3 and R4 are halogen chlorine, chlorine, phosphorus trichloride, phosphorus oxychloride, phosphorus pentachloride, N-chlorosuccinimide (NCS), a mixture of concentrated hydrochloric acid and anhydrous zinc chloride and Vilesmier-Haack reagent chlorination reagent are used for chlorination; when R3 and R4 are halogen bromine, bromine, hydrogen bromide, sodium bromide, N-bromosuccinimide (NBS), perbrominated pyridine hydrobromide (PHP), dibromohydantoin (DBDMH) and tetrabromocyclopentane (TBCO) bromination reagents are used for bromination; when R3 and R4 are halogen iodine, iodine and N-iodosuccinimide (NIS) iodination reagents are used for bromination.

[0038] Further, the R2 is a carboxyl group or a C1-C 12 Any of the alkyl groups.

[0039] Furthermore, the sulfonation is any one of concentrated sulfuric acid, oleum, chlorosulfonic acid or sulfur trichloride; the alkali fusion is sodium hydroxide, potassium hydroxide or a mixture of sodium hydroxide and potassium hydroxide in a certain proportion.

[0040] Furthermore, the hydrolysis reaction temperature of the compound 1 is 0-100 degrees, and the catalyst selected for the hydrolysis reaction is any one of chain polyethylene glycol, chain polyethylene glycol dialkyl ether cyclic crown ethers, 18 crown 6, 15 crown 5, cyclodextrin, benzyltriethylammonium chloride (TEBA), tetrabutylammonium bromide (TBAB), tetrabutylammonium chloride, tetrabutylammonium hydrogen sulfate, trioctylmethylammonium chloride, dodecyltrimethylammonium chloride, tetradecyltrimethylammonium chloride, tertiary amine R4NX, pyridine, tributylamine, quaternary ammonium base or quaternary phosphonium salt.

[0041] Furthermore, the alkali melting temperature of the compound 2 is 220-450° C.; the alkali melting pressure of the compound 2 is 1.0-6.0 MPa.

[0042] Another technical problem to be solved by the present invention is to provide a method for preparing a gallic acid derivative, comprising compound 5, wherein the chemical structural formula of compound 5 is:

[0043]

[0044] The compound 1 is esterified to obtain the compound 5, and the chemical synthesis formula of the compound 5 is:

[0045]

[0046] The compound 5 is esterified with gallic acid, ethanol and propanol to obtain gallic acid ester;

[0047] The preparation method of compound 5 comprises the following steps:

[0048] C1. Add 3,5-dibromo-4-hydroxybenzoic acid into a solvent to prepare a 3,5-dibromo-4-hydroxybenzoic acid solution;

[0049] C2. According to a certain ratio, add liquid alkali into the reactor first, add phase transfer catalyst benzyltriethylammonium chloride, slowly add the prepared 3,5-dibromo-4-hydroxybenzoic acid solution, heat to 100-200 degrees, the pressure in the reactor is 0.4-1.5MPa, maintain for 3-6 hours, continue stirring and keep warm for 3 hours;

[0050] C3, cool down to 75-80 degrees, transfer the material to the acid hydrolysis kettle, add 30-40% sulfuric acid solution, and after passing the test, cool down to 0 degrees; stir for 2 hours, and filter to obtain the crude product;

[0051] C4, the crude product is transferred into the solvent system in the crystallization kettle, heated to dissolve, and then crystallized, and the gallic acid product is obtained by filtration, with a yield of 80%;

[0052] C5. Take the gallic acid obtained in C4, and carry out esterification reaction with ethanol and propanol respectively. After the esterification reaction is completed, ethyl gallate and propyl gallate are obtained respectively.

[0053] Furthermore, the esterification temperature of the compound 5 is 20-170° C.; the esterification water-carrying agent for the esterification reaction of the compound 5 is any one of benzene, toluene, xylene, cyclohexane, n-hexane or petroleum ether.

[0054] Furthermore, the esterification catalyst for the esterification reaction in the compound 5 is any one of sulfuric acid, phosphoric acid, p-toluenesulfonic acid, a strong acid polymer or an acidic composite catalyst.

[0055] Compared with the prior art, the present invention provides a method for preparing gallic acid and its derivatives, which has the following beneficial effects:

[0056] 1. The preparation method of gallic acid and its derivatives is to synthesize 3,5-dihalogenated-4-hydroxybenzoic acid by halogenation and obtain 3,4,5-trihydroxybenzoic acid by hydrolysis. The process is simple and easy to implement.

[0057] 2. The preparation method of gallic acid and its derivatives adopts p-hydroxybenzoic acid as the starting material and the traditional sulfonation alkali fusion method. The process is mature and stable, the reaction process is simple, the raw materials are easily available, the product yield is high, the required equipment is conventional equipment, and industrial preparation is easy to achieve.

[0058] 3. The preparation method of gallic acid and its derivatives adopts a composite esterification catalyst, so the esterification yield is high and the product quality is good.

[0059] 4. The preparation method of gallic acid and its derivatives, through the careful design of various conditions in each step of the reaction route, has sufficient reaction, high conversion rate and economical cost. The gallic acid and its derivatives prepared by the above preparation method will be a good supplement to the preparation of gallic acid from the existing natural raw material gallic tannic acid in China, will expand the export scale of domestic gallic acid products, and replace the import of some antioxidants and other products. DETAILED DESCRIPTION

[0060] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0061] Embodiment 1:

[0062] A method for preparing gallic acid in this embodiment includes compound 1 and compound 3. The chemical structural formulas of compound 1 and compound 3 are as follows:

[0063]

[0064] In the formula: R1 is a hydroxyl group; R2 is a carboxyl group or an alkyl group; R3 and R4 are halogens (Cl, Br, I);

[0065] Compound 1 is hydrolyzed under certain conditions to obtain compound 3, and the chemical synthesis formula of compound 3 is:

[0066]

[0067] Compound 3 uses 3,5-dihalogenated-4-hydroxybenzoic acid as a raw material and is hydrolyzed to obtain gallic acid;

[0068] The preparation method of compound 3 comprises the following steps:

[0069] A1. Add 3,5-dibromo-4-hydroxybenzoic acid into a solvent to prepare a 3,5-dibromo-4-hydroxybenzoic acid solution;

[0070] A2. According to a certain ratio, add liquid alkali into the reactor first, add phase transfer catalyst benzyltriethylammonium chloride, slowly add the prepared 3,5-dibromo-4-hydroxybenzoic acid solution, heat to 100-200 degrees, the pressure in the reactor is 0.4-1.5MPa, maintain for 3-6 hours, and continue stirring and keeping warm for 3 hours;

[0071] A3, cool down to 75-80 degrees, transfer the material to the acid hydrolysis kettle, add 30-40% sulfuric acid solution, after passing the test, cool down to 0 degrees; stir for 2 hours, filter to get the crude product;

[0072] A4. The crude product was transferred into the solvent system in the crystallization kettle, heated to dissolve, and then crystallized. The gallic acid product was filtered to obtain a yield of 80%.

[0073] Wherein, R3 and R4 are any one of halogen chlorine, halogen bromine or halogen iodine.

[0074] It should be noted that when R3 and R4 are halogen chlorine, thionyl chloride, chlorine, phosphorus trichloride, phosphorus oxychloride, phosphorus pentachloride, N-chlorosuccinimide (NCS), a mixture of concentrated hydrochloric acid and anhydrous zinc chloride and Vilesmier-Haack reagent chlorination reagents are used for chlorination; when R3 and R4 are halogen bromine, bromine, hydrogen bromide, sodium bromide, N-bromosuccinimide (NBS), perbrominated pyridine hydrobromide (PHP), dibromohydantoin (DBDMH) and tetrabromocyclopentane (TBCO) bromination reagents are used for bromination; when R3 and R4 are halogen iodine, iodine and N-iodosuccinimide (NIS) iodination reagents are used for bromination.

[0075] Among them, the hydrolysis reaction temperature of compound 1 is 0-100 degrees, and the catalyst selected for the hydrolysis reaction is any one of chain polyethylene glycol, chain polyethylene glycol dialkyl ether cyclic crown ethers, 18 crown 6, 15 crown 5, cyclodextrin, benzyltriethylammonium chloride (TEBA), tetrabutylammonium bromide (TBAB), tetrabutylammonium chloride, tetrabutylammonium hydrogen sulfate, trioctylmethylammonium chloride, dodecyltrimethylammonium chloride, tetradecyltrimethylammonium chloride, tertiary amine R4NX, pyridine, tributylamine, quaternary ammonium base or quaternary phosphonium salt.

[0076] It should be noted that the preferred hydrolysis temperature for the hydrolysis of compound 1 is 30-85 degrees; the preferred catalyst for the hydrolysis of compound 1 is tetrabutylammonium bromide (TBAB).

[0077] Embodiment 2:

[0078] A method for preparing gallic acid in this embodiment includes compound 1 and compound 3. The chemical structural formulas of compound 1 and compound 3 are as follows:

[0079]

[0080] In the formula: R1 is a hydroxyl group; R2 is a carboxyl group or an alkyl group; R3 and R4 are halogens (Cl, Br, I);

[0081] Compound 1 is hydrolyzed under certain conditions to obtain compound 3, and the chemical synthesis formula of compound 3 is:

[0082]

[0083] Compound 3 uses 3,5-dihalogenated-4-hydroxybenzoic acid as a raw material and is hydrolyzed to obtain gallic acid;

[0084] The preparation method of compound 3 comprises the following steps:

[0085] A1. Add 3,5-dibromo-4-hydroxybenzoic acid into a solvent to prepare a 3,5-dibromo-4-hydroxybenzoic acid solution;

[0086] A2. According to a certain ratio, add liquid alkali into the reactor first, add phase transfer catalyst tetrabutylammonium bromide, slowly add the prepared 3,5-dibromo-4-hydroxybenzoic acid solution, heat to 100-200 degrees, the pressure in the reactor is 0.4-1.5MPa, maintain for 3-6 hours, and continue stirring and keeping warm for 5 hours;

[0087] A3, cool down to 60-65 degrees, transfer the material to the acid hydrolysis kettle, add 60-80% sulfuric acid solution, and after passing the test, cool down to 0 degrees; stir for 2 hours, and filter to obtain the crude product;

[0088] A4. The crude product was transferred into the solvent system in the crystallization kettle, heated to dissolve, and then crystallized. The gallic acid product was filtered to obtain a yield of 86%.

[0089] Wherein, R3 and R4 are any one of halogen chlorine, halogen bromine or halogen iodine.

[0090] It should be noted that when R3 and R4 are halogen chlorine, thionyl chloride, chlorine, phosphorus trichloride, phosphorus oxychloride, phosphorus pentachloride, N-chlorosuccinimide (NCS), a mixture of concentrated hydrochloric acid and anhydrous zinc chloride and Vilesmier-Haack reagent chlorination reagents are used for chlorination; when R3 and R4 are halogen bromine, bromine, hydrogen bromide, sodium bromide, N-bromosuccinimide (NBS), perbrominated pyridine hydrobromide (PHP), dibromohydantoin (DBDMH) and tetrabromocyclopentane (TBCO) bromination reagents are used for bromination; when R3 and R4 are halogen iodine, iodine and N-iodosuccinimide (NIS) iodination reagents are used for bromination.

[0091] Among them, the hydrolysis reaction temperature of compound 1 is 0-100 degrees, and the catalyst selected for the hydrolysis reaction is any one of chain polyethylene glycol, chain polyethylene glycol dialkyl ether cyclic crown ethers, 18 crown 6, 15 crown 5, cyclodextrin, benzyltriethylammonium chloride (TEBA), tetrabutylammonium bromide (TBAB), tetrabutylammonium chloride, tetrabutylammonium hydrogen sulfate, trioctylmethylammonium chloride, dodecyltrimethylammonium chloride, tetradecyltrimethylammonium chloride, tertiary amine R4NX, pyridine, tributylamine, quaternary ammonium base or quaternary phosphonium salt.

[0092] It should be noted that the preferred hydrolysis temperature for the hydrolysis of compound 1 is 30-85 degrees; the preferred catalyst for the hydrolysis of compound 1 is tetrabutylammonium bromide (TBAB).

[0093] Embodiment three:

[0094] A method for preparing gallic acid in this embodiment includes compound 2 and compound 4. The chemical structural formulas of compound 2 and compound 4 are as follows:

[0095]

[0096] Compound 2 is subjected to secondary sulfonation and alkali fusion to obtain compound 4, and the chemical synthesis formula of compound 4 is:

[0097]

[0098] In the formula, the substituent R1 is a hydroxyl group, and the substituent R2 is any one of a carboxyl group or a C1-C18 alkyl group;

[0099] Compound 4 uses p-hydroxybenzoic acid as a raw material, and undergoes secondary sulfonation, alkali fusion and acid precipitation to obtain gallic acid;

[0100] The preparation method of compound 4 comprises the following steps:

[0101] B1. Add p-hydroxybenzoic acid, concentrated sulfuric acid and oleum in a molar ratio of 1:4.2:4.0 into a reactor, heat to 120-170°C, control the free acid at 1-3%, use concentrated sulfuric acid for monosulfonation, and use oleum for disulfonation, which is completed in about 10 hours or the sulfonation yield is 85%;

[0102] B2, the sulfonated liquid is treated with liquid alkali to obtain crude sodium sulfonate, which is filtered and precipitated for use; the neutralization yield is 98-99%;

[0103] B3, add the required molar amount of caustic soda flakes, when the temperature in the alkali melting kettle rises to 350 degrees, start stirring, start to slowly add sodium benzenesulfonate, keep the temperature in the reactor at 350-370 degrees, continue stirring for 3 hours; control the free alkali to 1-3%; pass water vapor into the upper part of the alkali melting kettle for protection to prevent side reactions such as oxidation and coking;

[0104] B4, put the material with good alkali fusion reaction into water with a volume 3 times that of the alkali fusion material, and clarify and separate it after dilution; the sodium phenolate solution is acidified; the solid sodium sulfite is filtered, washed, and vacuum filtered to obtain a sodium sulfite byproduct for sulfonation neutralization;

[0105] B5, control the vacuum degree to 26.67-53.33 kPa; when the sulfur dioxide produced in the neutralization section is sent to the acidification pot, the diluted sodium phenolate solution is continuously added to the acidification pot, and the reaction temperature is about 70°C; the reaction is controlled to be slightly acidic (pH=6-7); the crude phenol solution and the sodium sulfite solution are separated by clarification and separation; the crude phenol solution is extracted and purified, and the sodium sulfite solution is used for neutralization;

[0106] B6. When sulfuric acid cannot be used for sulfuric acid dioxide, sulfuric acid or hydrochloric acid can be used for acidification; 93% sulfuric acid is added evenly over 0.75-1h, the temperature is controlled at 60-75°C, and the end point control is the same as that for sulfuric acid dioxide; the acidification yield is 95-98%%;

[0107] B7. The crude 3,4,5-trihydroxybenzoic acid is extracted and purified 2-3 times with a mixed solvent of toluene + fatty alcohol to obtain a product; the product purity is ≥98.0%, and the total yield calculated based on p-hydroxybenzoic acid is 40-50%; the product in the mother liquor is reserved for subsequent treatment.

[0108] Wherein, R2 is carboxyl or C1-C 12 Any of the alkyl groups.

[0109] Among them, the sulfonation is any one of concentrated sulfuric acid, fuming sulfuric acid, chlorosulfonic acid or sulfur trichloride; the alkali fusion adopts sodium hydroxide, potassium hydroxide or a mixture of sodium hydroxide and potassium hydroxide in a certain proportion.

[0110] The alkali melting temperature of compound 2 is 220-450°C; and the alkali melting pressure of compound 2 is 1.0-6.0MPa.

[0111] It should be noted that the preferred alkali melting temperature of compound 2 is 360-390°C; the preferred alkali melting pressure of compound 2 is 2.0-5.0 MPa.

[0112] Embodiment 4:

[0113] A method for preparing gallic acid in this embodiment includes compound 2 and compound 4. The chemical structural formulas of compound 2 and compound 4 are as follows:

[0114]

[0115] Compound 2 is subjected to secondary sulfonation and alkali fusion to obtain compound 4, and the chemical synthesis formula of compound 4 is:

[0116]

[0117] In the formula, the substituent R1 is a hydroxyl group, and the substituent R2 is any one of a carboxyl group or a C1-C18 alkyl group;

[0118] Compound 4 uses p-hydroxybenzoic acid as a raw material, and undergoes secondary sulfonation, alkali fusion and acid precipitation to obtain gallic acid;

[0119] The preparation method of compound 4 comprises the following steps:

[0120] B1. Add p-hydroxybenzoic acid, concentrated sulfuric acid and oleum into the reactor in a molar ratio of 1:4.2:4.0, heat to 120-170°C, control the free acid at 1-3%, use concentrated sulfuric acid to carry out monosulfonation reaction; use the prepared sulfur trioxide solution to carry out disulfonation, which is completed in about 10 hours or the sulfonation yield is 88-92%;

[0121] B2. The sulfonated liquid is neutralized with sodium sulfite solution to obtain crude sodium sulfonate, which is filtered and precipitated for use; the sulfur dioxide produced by neutralization with sodium sulfite is transported to the acid precipitation process through a pipeline; the neutralization yield is 99%;

[0122] B3. Add the required molar amount of caustic soda flakes, when the temperature in the alkali melting kettle rises to 350 degrees, start stirring, slowly add sodium benzenesulfonate, keep the temperature in the reactor at 350-370 degrees, and continue stirring for 3 hours. Control the free alkali to 1-3%; pass water vapor into the upper part of the alkali melting kettle to prevent side reactions such as oxidation and coking;

[0123] B4, put the material with good alkali fusion reaction into water with a volume 3 times that of the alkali fusion material, and clarify and separate it after dilution; the sodium phenolate solution is acidified; the solid sodium sulfite is filtered, washed, and vacuum filtered to obtain a sodium sulfite byproduct for sulfonation neutralization;

[0124] B5, control the vacuum degree to 26.67-53.33 kPa, when the sulfur dioxide produced in the neutralization section is sent to the acidification pot, the diluted sodium phenolate solution is continuously added to the acidification pot, and the reaction temperature is about 70°C; the reaction is controlled to be slightly acidic (pH=6-7); the crude phenol solution and the sodium sulfite solution are separated by clarification and separation; the crude phenol solution is to be extracted and purified, and the sodium sulfite solution is used for neutralization;

[0125] B6. When sulfuric acid with dioxide cannot be used for acidification, sulfuric acid or hydrochloric acid can be used for acidification; add about 93% sulfuric acid evenly over 0.75-1h, control the temperature at 60-75℃, and control the end point in the same way as sulfuric acid with dioxide. The acidification yield is 95-98%;

[0126] B7. The crude 3,4,5-trihydroxybenzoic acid is extracted and purified 2-3 times with a mixed solvent of petroleum ether and fatty alcohol to obtain a product; the product purity is ≥99.0%, and the total yield calculated based on p-hydroxybenzoic acid is 50-60%; the product in the mother liquor is reserved for subsequent treatment.

[0127] Wherein, R2 is carboxyl or C1-C 12 Any of the alkyl groups.

[0128] Among them, the sulfonation is any one of concentrated sulfuric acid, fuming sulfuric acid, chlorosulfonic acid or sulfur trichloride; the alkali fusion adopts sodium hydroxide, potassium hydroxide or a mixture of sodium hydroxide and potassium hydroxide in a certain proportion.

[0129] The alkali melting temperature of compound 2 is 220-450°C; and the alkali melting pressure of compound 2 is 1.0-6.0MPa.

[0130] It should be noted that the preferred alkali melting temperature of compound 2 is 360-390°C; the preferred alkali melting pressure of compound 2 is 2.0-5.0 MPa.

[0131] Embodiment five:

[0132] A method for preparing a gallic acid derivative in this embodiment includes compound 5, and the chemical structure of compound 5 is:

[0133]

[0134] Compound 1 is esterified to obtain compound 5, and the chemical synthesis formula of compound 5 is:

[0135]

[0136] Compound 5 was esterified with gallic acid and ethanol to obtain gallic acid ester;

[0137] The preparation method of compound 5 comprises the following steps:

[0138] C1. Add 3,5-dibromo-4-hydroxybenzoic acid into a solvent to prepare a 3,5-dibromo-4-hydroxybenzoic acid solution;

[0139] C2. According to a certain ratio, add liquid alkali into the reactor first, add phase transfer catalyst benzyltriethylammonium chloride, slowly add the prepared 3,5-dibromo-4-hydroxybenzoic acid solution, heat to 100-200 degrees, the pressure in the reactor is 0.4-1.5MPa, maintain for 3-6 hours, continue stirring and keep warm for 3 hours;

[0140] C3, cool down to 75-80 degrees, transfer the material to the acid hydrolysis kettle, add 30-40% sulfuric acid solution, and after passing the test, cool down to 0 degrees; stir for 2 hours, and filter to obtain the crude product;

[0141] C4, the crude product is transferred into the solvent system in the crystallization kettle, heated to dissolve, and then crystallized, and the gallic acid product is obtained by filtration, with a yield of 80%;

[0142] C5, take the gallic acid obtained in C4, feed it according to the molar ratio of gallic acid to ethanol of 1:1.5-2.0, add water-carrying n-hexane, add a quantitative acid catalyst; heat to the azeotropic temperature of n-hexane and water, keep reflux; detect the disappearance of gallic acid in the reaction system, and regard the reaction as complete. Cool the reaction mixture to 10-20 degrees, filter; the filtrate is the crude product of propyl gallate;

[0143] C6, the obtained filtrate is subjected to reduced pressure distillation to remove n-propanol and n-hexane, then pure water (1 times the mass of the crude product) is added to the reactor, heated to 80-90°C, activated carbon (1-3% of the mass of the crude product) is added, stirred for 1 hour, and filtered;

[0144] C7. The solution is returned to the crystallization kettle, cooled to 40-50°C, the stirring speed is adjusted, the temperature is gradually reduced to 0°C, cooled and crystallized, and filtered to obtain ethyl gallate; after the product is vacuum dried, the calculated yield is 91-92%.

[0145] The esterification temperature of compound 5 is 20-170° C.; the esterification water-carrying agent for the esterification reaction of compound 5 is any one of benzene, toluene, xylene, cyclohexane, n-hexane or petroleum ether.

[0146] The esterification catalyst of the esterification reaction in compound 5 is any one of sulfuric acid, phosphoric acid, p-toluenesulfonic acid, a strong acid polymer or an acid composite catalyst.

[0147] It should be noted that the preferred water-carrying agent is toluene and cyclohexane, and the preferred catalyst is p-toluenesulfonic acid and a strong acid polymer.

[0148] Embodiment six:

[0149] A method for preparing a gallic acid derivative in this embodiment includes compound 5, and the chemical structure of compound 5 is:

[0150]

[0151] Compound 1 is esterified to obtain compound 5, and the chemical synthesis formula of compound 5 is:

[0152]

[0153] Compound 5 was esterified with gallic acid and propanol to obtain gallic acid ester;

[0154] The preparation method of compound 5 comprises the following steps:

[0155] C1. Add 3,5-dibromo-4-hydroxybenzoic acid into a solvent to prepare a 3,5-dibromo-4-hydroxybenzoic acid solution;

[0156] C2. According to a certain ratio, add liquid alkali into the reactor first, add phase transfer catalyst benzyltriethylammonium chloride, slowly add the prepared 3,5-dibromo-4-hydroxybenzoic acid solution, heat to 100-200 degrees, the pressure in the reactor is 0.4-1.5MPa, maintain for 3-6 hours, continue stirring and keep warm for 3 hours;

[0157] C3, cool down to 75-80 degrees, transfer the material to the acid hydrolysis kettle, add 30-40% sulfuric acid solution, and after passing the test, cool down to 0 degrees; stir for 2 hours, and filter to obtain the crude product;

[0158] C4, the crude product is transferred into the solvent system in the crystallization kettle, heated to dissolve, and then crystallized, and the gallic acid product is obtained by filtration, with a yield of 80%;

[0159] C5, taking the gallic acid obtained in C4, feeding it according to the molar ratio of gallic acid to n-propanol of 1:1.3-2.0, adding cyclohexane with water, and adding a quantitative acid catalyst; heating to the azeotropic temperature of cyclohexane and water, keeping reflux; detecting the disappearance of gallic acid in the reaction system, it is considered that the reaction is over; cooling the reaction mixture to 20-30 degrees, filtering; the filtrate is the crude product of propyl gallate;

[0160] C6. The obtained filtrate is subjected to reduced pressure distillation to remove n-propanol and cyclohexane, and then pure water 2-3 times the mass of the crude product is added to the reactor, and heated to 80-90°C to dissolve all the solids; activated carbon 1-3% of the mass of the crude product is added, stirred for 1 hour, and filtered;

[0161] C7. The solution is returned to the crystallization kettle, cooled to 40-50°C, the stirring speed is adjusted, the temperature is gradually reduced to 0°C, cooled and crystallized, and filtered to obtain propyl gallate; after the product is vacuum dried, the calculated yield is 86-88%.

[0162] The esterification temperature of compound 5 is 20-170° C.; the esterification water-carrying agent for the esterification reaction of compound 5 is any one of benzene, toluene, xylene, cyclohexane, n-hexane or petroleum ether.

[0163] The esterification catalyst of the esterification reaction in compound 5 is any one of sulfuric acid, phosphoric acid, p-toluenesulfonic acid, a strong acid polymer or an acid composite catalyst.

[0164] It should be noted that the preferred water-carrying agent is toluene and cyclohexane, and the preferred catalyst is p-toluenesulfonic acid and a strong acid polymer.

[0165] The beneficial effects of the present invention are:

[0166] The preparation method of gallic acid and its derivatives adopts halogenation to synthesize 3,5-dihalogenated-4-hydroxybenzoic acid, and hydrolyzes it to obtain 3,4,5-trihydroxybenzoic acid, and the process is simple and easy to implement; by adopting p-hydroxybenzoic acid as a starting raw material and adopting a traditional sulfonation alkali fusion method, the process is mature and stable, the reaction process is simple, the raw materials are easily available, the product yield is high, the required equipment is conventional equipment, and industrial preparation is easy to achieve.

[0167] The preparation method of gallic acid and its derivatives has high esterification yield and good product quality by adopting a composite esterification catalyst; the reaction is sufficient, the conversion rate is high, and the cost is economical by carefully designing the conditions of each step of the reaction route. The gallic acid and its derivatives prepared by the above preparation method will be a good supplement to the preparation of gallic acid from the existing natural raw material gallic tannic acid in China, and will expand the export scale of domestic gallic acid products and replace the import of some antioxidants and other products.

[0168] Those skilled in the art will readily appreciate other embodiments of the present disclosure after considering the specification and practicing the invention disclosed herein. The present disclosure is intended to cover any variations, uses or adaptations of the present disclosure that follow the general principles of the present disclosure and include common knowledge or customary techniques in the art that are not disclosed in the present disclosure. The description and examples are to be considered exemplary only, and the true scope and spirit of the present disclosure are indicated by the following claims.

[0169] The above description is only a preferred embodiment of the present disclosure and is not intended to limit the present disclosure. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present disclosure shall be included in the scope of protection of the present disclosure.

Claims

1. A method for preparing gallic acid, characterized in that: Including compound 1, compound 2, compound 3 and compound 4, the chemical structural formulas of compound 1, compound 2, compound 3 and compound 4 are as follows; In the formula: R1 is a hydroxyl group; R2 is a carboxyl group or an alkyl group; R3 and R4 are halogens (Cl, Br, I); The compound 1 is hydrolyzed under certain conditions to obtain compound 3, and the chemical synthesis formula of compound 3 is: The compound 3 uses 3,5-dihalogenated-4-hydroxybenzoic acid as a raw material and is hydrolyzed to obtain gallic acid; The compound 2 is subjected to secondary sulfonation and alkali fusion to obtain compound 4, and the chemical synthesis formula of compound 4 is: In the formula, the substituent R1 is a hydroxyl group, and the substituent R2 is any one of a carboxyl group or a C1-C18 alkyl group; The compound 4 uses p-hydroxybenzoic acid as a raw material, and undergoes secondary sulfonation and alkali fusion acid precipitation to obtain gallic acid; The preparation method of compound 3 comprises the following steps: A1. Add 3,5-dibromo-4-hydroxybenzoic acid into a solvent to prepare a 3,5-dibromo-4-hydroxybenzoic acid solution; A2. According to a certain ratio, add liquid alkali into the reactor first, add phase transfer catalyst benzyltriethylammonium chloride, slowly add the prepared 3,5-dibromo-4-hydroxybenzoic acid solution, heat to 100-200 degrees, the pressure in the reactor is 0.4-1.5MPa, maintain for 3-6 hours, and continue stirring and keeping warm for 3 hours; A3, cool down to 75-80 degrees, transfer the material to the acid hydrolysis kettle, add 30-40% sulfuric acid solution, after passing the test, cool down to 0 degrees; stir for 2 hours, filter to get the crude product; A4. The crude product was transferred into the solvent system in the crystallization kettle, heated and dissolved, and then crystallized. The gallic acid product was filtered to obtain a yield of 80%; The preparation method of compound 4 comprises the following steps: B1. Add p-hydroxybenzoic acid, concentrated sulfuric acid and oleum in a molar ratio of 1:4.2:4.0 into a reactor, heat to 120-170°C, control the free acid at 1-3%, use concentrated sulfuric acid for monosulfonation, and use oleum for disulfonation, which is completed in about 10 hours or the sulfonation yield is 85%; B2, the sulfonated liquid is treated with liquid alkali to obtain crude sodium sulfonate, which is filtered and precipitated for use; the neutralization yield is 98-99%; B3, add the required molar amount of caustic soda flakes, when the temperature in the alkali melting kettle rises to 350 degrees, start stirring, start to slowly add sodium benzenesulfonate, keep the temperature in the reactor at 350-370 degrees, continue stirring for 3 hours; control the free alkali to 1-3%; pass water vapor into the upper part of the alkali melting kettle for protection to prevent side reactions such as oxidation and coking; B4, put the material with good alkali fusion reaction into water with a volume 3 times that of the alkali fusion material, and clarify and separate it after dilution; the sodium phenolate solution is acidified; the solid sodium sulfite is filtered, washed, and vacuum filtered to obtain a sodium sulfite byproduct for sulfonation neutralization; B5, control the vacuum degree to 26.67-53.33 kPa; when the sulfur dioxide produced in the neutralization section is sent to the acidification pot, the diluted sodium phenolate solution is continuously added to the acidification pot, and the reaction temperature is about 70°C; the reaction is controlled to be slightly acidic (pH=6-7); the crude phenol solution and the sodium sulfite solution are separated by clarification and separation; the crude phenol solution is extracted and purified, and the sodium sulfite solution is used for neutralization; B6. When sulfuric acid cannot be used for sulfuric acid dioxide, sulfuric acid or hydrochloric acid can be used for acidification; 93% sulfuric acid is added evenly over 0.75-1h, the temperature is controlled at 60-75°C, and the end point control is the same as that for sulfuric acid dioxide; the acidification yield is 95-98%%; B7, crude 3,4,5-trihydroxybenzoic acid, extracted and purified with toluene + fatty alcohol mixed solvent 2-3 times to obtain the product; The product purity is ≥98.0%, and the total yield calculated based on p-hydroxybenzoic acid is 40-50%; the product in the mother liquor is reserved for subsequent treatment.

2. A method for preparing gallic acid according to claim 1, characterized in that: The R3 and R4 are any one of halogen chlorine, halogen bromine or halogen iodine.

3. A method for preparing gallic acid according to claim 2, characterized in that: When R3 and R4 are halogen chlorine, chlorine, phosphorus trichloride, phosphorus oxychloride, phosphorus pentachloride, N-chlorosuccinimide (NCS), a mixture of concentrated hydrochloric acid and anhydrous zinc chloride and Vilesmier-Haack reagent are used for chlorination; when R3 and R4 are halogen bromine, bromine, hydrogen bromide, sodium bromide, N-bromosuccinimide (NBS), perbrominated pyridine hydrobromide (PHP), dibromohydantoin (DBDMH) and tetrabromocyclopentane (TBCO) are used for bromination; when R3 and R4 are halogen iodine, iodine and N-iodosuccinimide (NIS) are used for bromination.

4. A method for preparing gallic acid according to claim 1, characterized in that: The R2 is a carboxyl group or a C1-C 12 Any of the alkyl groups.

5. A method for preparing gallic acid according to claim 4, characterized in that: The sulfonation is any one of concentrated sulfuric acid, oleum, chlorosulfonic acid or sulfur trichloride; the alkali fusion is sodium hydroxide, potassium hydroxide or a mixture of sodium hydroxide and potassium hydroxide in a certain proportion.

6. A method for preparing gallic acid according to claim 1, characterized in that: The hydrolysis reaction temperature of the compound 1 is 0-100 degrees, and the catalyst selected for the hydrolysis reaction is any one of chain polyethylene glycol, chain polyethylene glycol dialkyl ether cyclic crown ethers, 18 crown 6, 15 crown 5, cyclodextrin, benzyltriethylammonium chloride (TEBA), tetrabutylammonium bromide (TBAB), tetrabutylammonium chloride, tetrabutylammonium hydrogen sulfate, trioctylmethylammonium chloride, dodecyltrimethylammonium chloride, tetradecyltrimethylammonium chloride, tertiary amine R4N X, pyridine, tributylamine, quaternary ammonium base or quaternary phosphonium salt.

7. A method for preparing gallic acid according to claim 1, characterized in that: The alkali melting temperature of the compound 2 is 220-450° C.; the alkali melting pressure of the compound 2 is 1.0-6.0 MPa.

8. A method for preparing a gallic acid derivative, using the method for preparing gallic acid according to claim 1, characterized in that: Including compound 5, the chemical structural formula of compound 5 is: The compound 1 is esterified to obtain the compound 5, and the chemical synthesis formula of the compound 5 is: The compound 5 is esterified with gallic acid, ethanol and propanol to obtain gallic acid ester; The preparation method of compound 5 comprises the following steps: C1. Add 3,5-dibromo-4-hydroxybenzoic acid into a solvent to prepare a 3,5-dibromo-4-hydroxybenzoic acid solution; C2. According to a certain ratio, add liquid alkali into the reactor first, add phase transfer catalyst benzyltriethylammonium chloride, slowly add the prepared 3,5-dibromo-4-hydroxybenzoic acid solution, heat to 100-200 degrees, the pressure in the reactor is 0.4-1.5MPa, maintain for 3-6 hours, continue stirring and keep warm for 3 hours; C3, cool down to 75-80 degrees, transfer the material to the acid hydrolysis kettle, add 30-40% sulfuric acid solution, and after passing the test, cool down to 0 degrees; stir for 2 hours, and filter to obtain the crude product; C4, the crude product is transferred into the solvent system in the crystallization kettle, heated to dissolve, and then crystallized, and the gallic acid product is obtained by filtration, with a yield of 80%; C5. Take the gallic acid obtained in C4, and carry out esterification reaction with ethanol and propanol respectively. After the esterification reaction is completed, ethyl gallate and propyl gallate are obtained respectively.

9. The method for preparing a gallic acid derivative according to claim 8, characterized in that: The esterification temperature of the compound 5 is 20-170° C.; the esterification water-carrying agent for the esterification reaction of the compound 5 is any one of benzene, toluene, xylene, cyclohexane, n-hexane or petroleum ether.

10. The method for preparing a gallic acid derivative according to claim 8, characterized in that: The esterification catalyst for the esterification reaction in the compound 5 is any one of sulfuric acid, phosphoric acid, p-toluenesulfonic acid, a strong acid polymer or an acid composite catalyst.

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