CN112824369B - High-yield vanillin synthesis process - Google Patents
High-yield vanillin synthesis process Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/65—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/02—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof
- C07C303/04—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof by substitution of hydrogen atoms by sulfo or halosulfonyl groups
- C07C303/06—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof by substitution of hydrogen atoms by sulfo or halosulfonyl groups by reaction with sulfuric acid or sulfur trioxide
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/02—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof
- C07C303/22—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof from sulfonic acids, by reactions not involving the formation of sulfo or halosulfonyl groups; from sulfonic halides by reactions not involving the formation of halosulfonyl groups
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Abstract
The invention provides a high-yield vanillin synthesis process, which comprises the following steps: 1) Mixing guaiacol, alkyl pyridine and a sulfonating agent to prepare a product 1; 2) Adding the product 1 and inorganic base into a reactor, dropwise adding a formylation reagent, and reacting to obtain a product 2; 3) And dissolving the product 2 in a solvent, adding acid, heating, stirring, cooling and purifying to obtain the target product vanillin. The route of the invention has the outstanding advantages of fewer byproducts, high synthesis yield, mild reaction conditions and the like, and simultaneously solves the problem of low sulfonation para-position yield, thereby having stronger reference significance.
Description
Technical Field
The invention relates to a vanillin synthesis process, in particular to a high-yield vanillin synthesis process, and belongs to the technical field of organic synthesis.
Background
Vanillin, also known as vanillin, is the edible synthetic flavor with the largest yield in the world at present, and the annual consumption is about 2.8 ten thousand tons. The vanillin is obtained mainly by three ways of natural extraction, chemical synthesis and biological fermentation. Among them, chemical synthesis is the most widespread source for obtaining vanillin, and the production methods are classified into guaiacol method, p-cresol method, lignin method, coniferin method, eugenol method, p-hydroxybenzaldehyde method, xanthophyll method, and the like. Guaiacol is low in price and wide in source, and gradually becomes the mainstream of vanillin synthesis process, and more than 90% of vanillin manufacturers currently adopt guaiacol as a raw material.
The method for synthesizing vanillin by using guaiacol as a raw material mainly comprises a glyoxylic acid method and a formaldehyde method, wherein the glyoxylic acid method is most widely applied and most relevant researches are carried out, chinese patent CN102010312A introduces a glyoxylic acid method process route in detail, the process comprises three steps of condensation, oxidation and decarboxylation, and the yield is about 65-75%. The biggest defects of the route are that the reaction route is long, the waste water amount is large, the process is complicated, and generally, the method is difficult to be greatly improved in a short period. The reaction route of the formaldehyde method is as follows: guaiacol and formaldehyde (or urotropine) firstly react by taking hydrochloric acid as a catalyst to obtain vanillyl alcohol, and then the vanillyl alcohol and p-nitrosodimethylaniline react by oxidation to obtain vanillin. European patent EP0485613A1 describes the p-methylolation of phenols, particularly guaiacol, by reacting guaiacol with formaldehyde in an alcoholic organic solvent and in the presence of sodium hydroxide and a quaternary ammonium compound (e.g. tetramethylammonium hydroxide), but this reaction requires two successive steps of reduced pressure distillation to remove excess solvent, and thus has the disadvantage of a cumbersome process route. In addition, the process has the disadvantages of relatively high reaction temperatures, relatively long reaction times and low yields.
The Reimer-Tiemann reaction is a commonly used synthetic method in organic chemistry, and Douglas E.Armstrong, donald H.Richardson, the Reimer-Tiemann reaction, journal of Chemical Society,1993,60 (2): 1-36 describe The reaction in detail, mainly based on The principle that phenol and chloroform are heated in an alkaline solution to form ortho-or para-hydroxybenzaldehyde, and heterocyclic compounds such as quinoline and pyrrole containing hydroxyl can also be used for The reaction, but The products are mainly ortho-position. In order to improve the yield of para-vanillin, plum pillar, crepe, reimer-Tiemann reaction for synthesizing vanillin, chemical world, 1991 (01): 20-21, it is proposed that triethylamine is added into the reaction system as a catalyst, so that the reaction activity and the uniformity of the reaction solution can be effectively improved. However, the overall yield is still not ideal and only reaches 76%, and in addition, the method has the biggest problem that more than 20% of ortho-vanillin is generated, the boiling points of the vanillin and the ortho-vanillin are not greatly different, and the vanillin belongs to a heat-sensitive material, so that great difficulty is caused for later separation and purification.
Disclosure of Invention
The invention aims to provide a high-yield vanillin synthesis process, which comprises the steps of occupying the ortho position by using a self-synthesized sulfonating reagent, generating para-aldehyde group by using the obtained compound through a Reimer-Tiemann reaction, and removing a protecting group by using the characteristic that a sulfonic acid group is easy to remove by heat, thereby generating para-vanillin with high yield.
Although sulfonic acid groups are often used as end-capping protective groups due to their easy removal properties, it is known from literature reports that sulfonation of phenols at high temperatures easily produces para-position products, while ortho-position and para-position account for half of the low-temperature products (basic organic chemistry, ancient edition, page 837), which is disadvantageous to the concept of the present invention that ortho-position occupancy is first performed to regenerate para-position vanillin. Therefore, in order to obtain higher yields of the guaiacol sulfonated ortho product, certain strategies must be employed in addition to operation at low temperatures.
Pyridine is taken as a typical aromatic heterocyclic compound, and a nitrogen atom in the molecule of the pyridine has a pair of unshared electrons which do not participate in a pi system, so that the pyridine has certain nucleophilic ability. The invention combines pyridine and sulfonic group to generate sulfonic pyridine complex, which can be used as mild sulfonation reagent in vanillin synthesis system to improve the ortho-position selectivity of the space occupying group.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
a high-yield vanillin synthesis process comprises the following steps:
1) Mixing guaiacol, alkyl pyridine and a sulfonating agent to prepare a product 1; the alkyl pyridine and the sulfonating agent are contacted to generate a sulfonic pyridine complex, which is shown as the following formula:
guaiacol generates a compound 2-hydroxy-3 methoxybenzenesulfonic acid occupying the position of an ortho-position sulfonic group under the action of a sulfonic pyridine complex, namely a product 1;
2) Adding the product 1 and inorganic base into a reactor, dropwise adding a formylation reagent, and reacting to obtain a compound 5-aldehyde-2-hydroxy-3-methoxybenzenesulfonic acid, namely a product 2;
3) And dissolving the product 2 in a solvent, adding acid, heating, stirring, cooling and purifying to obtain the target product vanillin.
The structural expression of the reaction process is as follows:
further, the molar ratio of the guaiacol, the alkyl pyridine and the sulfonating agent in the step 1) is 1 (0.5-2): (0.5-2), preferably 1 (1-1.6): (1-1.5).
Further, the raw materials in the step 1) are mixed and then reacted at a temperature of-10 to 10 ℃, preferably at a temperature of 0 ℃ in an ice bath, and the reaction time is 15 to 80min, preferably 40 to 60min.
Further, the structural expression of the alkyl pyridine in the step 1) is as follows:
wherein R is 1 、R 2 Each represents an alkyl or alkoxy group having 0 to 1 carbon atoms, R 1 And R 2 Can be simultaneously 0 or simultaneously 1; the alkyl pyridine is preferably at least one of pyridine, 2-methylpyridine, 3-methylpyridine, 2-methoxypyridine, 3-methoxypyridine and 2, 3-dimethoxypyridine;
in the step 1), the sulfonating agent is fuming sulfuric acid or a sulfuric acid solution with the mass fraction of 50-98%, and 98% concentrated sulfuric acid is preferred;
the reaction solvent in the step 1) is at least one of toluene, ethylbenzene, tetrahydrofuran, DMF and diethyl ether, and preferably one or two of toluene and tetrahydrofuran.
The post-treatment mode of the step 1) is as follows: adding deionized water to quench the reaction, and then adding an organic solvent to extract a product 1; the organic solvent is at least one of n-hexane, petroleum ether, butyl acetate and dichloromethane, and the preferable extraction solvent is n-hexane or petroleum ether.
Further, the molar ratio of the product 1, the inorganic base and the formylation reagent in the step 2) is 1:7 to 9:2.5 to 4, preferably 1.
Further, the reaction temperature of the step 2) is 50-120 ℃, preferably 60-80 ℃, and the reaction time is 5-24 hours, preferably 8-12 hours.
Further, the inorganic base in the step 2) is one or a mixture of any two of sodium hydroxide, potassium hydroxide, calcium hydroxide, potassium carbonate and sodium carbonate, preferably sodium hydroxide;
the formylation reagent in the step 2) is at least one of trichloromethane, tribromomethane and iodomethane, preferably trichloromethane;
the reaction solvent in the step 2) is at least one of methanol, ethanol, isopropanol and water, and preferably methanol water or ethanol water solution.
Further, the adding amount of the acid in the step 3) is regulated and controlled by pH, and the pH of the reaction system is 1.5-2.5.
Further, the reaction temperature in the step 3) is 30-80 ℃, preferably 30-50 ℃, and the reaction time is 10-60 min, preferably 30-40 min.
Further, the solvent in the step 3) is at least one of water, ethanol, DMF and methanol, preferably water;
the acid in the step 3) is dilute hydrochloric acid, dilute sulfuric acid or dilute nitric acid, and preferably dilute sulfuric acid.
The purification mode after the reaction in the step 3) is evaporation to dryness and extraction; the organic solvent for extraction is at least one of methyl tert-butyl ether, anhydrous diethyl ether and tetrahydrofuran, and preferably methyl tert-butyl ether.
The invention provides a brand new vanillin synthetic route, guaiacol firstly undergoes sulfonation reaction with sulfuric acid and alkyl pyridine, and a sulfonic acid end capping group can be generated at the ortho position of guaiacol hydroxyl due to the low reaction temperature and the ortho position selectivity of a sulfonic acid pyridine complex. Then carrying out Reimer-Tiemann reaction, because the ortho position is replaced by sulfonic group, the aldehyde group can only be added to para position to generate 5-sulfonic vanillin, and finally heating under acidic condition to remove sulfonic acid protecting group to obtain vanillin product. The route of the invention has the outstanding advantages of fewer byproducts, high synthesis yield, mild reaction conditions and the like, and simultaneously solves the problem of low sulfonation para-position yield, thereby having stronger reference significance.
Detailed Description
The present invention is further illustrated by the following specific examples, which are intended to be illustrative of the invention and are not to be construed as limiting the scope of the invention.
The examples and comparative examples relate to the following main raw materials and sources:
other raw materials and reagents may be commercially available unless otherwise specified.
The analytical test method adopted by the invention comprises the following steps:
the element analysis method adopts ICP-MS for detection, namely inductively coupled plasma mass spectrometry.
The column chromatography is carried out by adopting a forward silica gel column, and the column length is about 300mm.
The NMR spectrum was obtained using a Brucker Advance instrument at a frequency of 600MHz and TMS as an internal standard.
[ example 1 ]
Into a three-necked flask with a thermometer, 17.5g of pyridine and 300g of tetrahydrofuran were charged and the mixture was cooled in an ice bath at 0 ℃20g of 98% concentrated sulfuric acid is slowly dropped into the reaction system to obtain a pyridine sulfonic acid complex, and the element analysis is as follows: c37.49%, H3.78%, N8.74%, O29.97%, S20.02%. Then, 50g of guaiacol is dripped, reaction is continued for 15min after the dripping is finished, a small amount of water is added for quenching, and a product 1 is obtained after separation and purification. 50g of the compound 1 was dissolved in 120g of an aqueous ethanol solution, and 171.5g of a 40% sodium hydroxide solution and 71.6g of chloroform were added thereto, heated to 70 ℃ and reacted under these conditions for 10 hours, and isolated and purified to obtain a compound 2. Elemental analysis was as follows: c41.38%, H3.47%, O41.34%, S13.81%, nuclear magnetic results were as follows: 1 H NMR(600MHz,CDCl 3 ): δ 2.0 (1H), 3.83 (3H), 5.35 (1H), 7.27 (1H), 7.73 (1H), 9.88 (1H). Dissolving 40g of the compound 2 in 200g of water, dropwise adding a small amount of 30% dilute sulfuric acid into the water until the pH value is 2.0, stirring the mixture at 50 ℃ for 40min to separate out gray oily liquid, adding a certain amount of butyl acetate into the oily liquid to extract, and performing rotary evaporation and purification to obtain a vanillin product. Elemental analysis was as follows: c63.15%, H5.30%, O31.55%; the nuclear magnetic results are as follows: 1 H NMR(600MHz,CDCl 3 ): δ 3.83 (3H), 5.35 (1H), 7.25 (2H), 7.38 (1H), 9.61 (1H). The yield of vanillin (calculated by guaiacol) in the whole reaction process is about 92.15%.
[ example 2 ] A method for producing a polycarbonate
41.2g of 2-methylpyridine and 300g of toluene were added to a three-necked flask with a thermometer, and 112g of 70% concentrated sulfuric acid was slowly added dropwise to the reaction system under an ice bath condition at 0 ℃ to obtain a pyridinesulfonic acid complex, which was analyzed by the following elements: 41.37 percent of C, 4.63 percent of H, 8.04 percent of N, 27.55 percent of O and 18.41 percent of S. Then, 50g of guaiacol is dripped, after the dripping is finished, the reaction is continued for 50min, and then a small amount of water is added for extraction and extinction, and the compound 1 is obtained after separation and purification. 50g of the compound 1 was dissolved in 120g of an aqueous methanol solution, 220.5g of a 40% sodium hydroxide solution and 114.6g of chloroform were added thereto, and the mixture was heated to 50 ℃ to react for 12 hours under the conditions, and then, the compound 2 was isolated and purified. Dissolving 40g of the compound 2 in 200g of water, dropwise adding a small amount of 30% dilute sulfuric acid into the water until the pH value is 2.5, stirring the mixture at 50 ℃ for 40min to separate out gray oily liquid, adding a certain amount of butyl acetate into the oily liquid to extract, and performing rotary evaporation and purification to obtain a vanillin product. The yield of vanillin (calculated by guaiacol) in the whole reaction process is about 90.52%.
[ example 3 ]
51.5g of 3-methylpyridine and 300g of tetrahydrofuran are added into a three-necked flask with a thermometer, and 79.5g of 50% concentrated sulfuric acid is slowly dropped into the reaction system at-10 ℃ to obtain a pyridine sulfonic acid complex, wherein the elemental analysis is as follows: 41.37 percent of C, 4.63 percent of H, 8.04 percent of N, 27.55 percent of O and 18.41 percent of S. Then, 50g of guaiacol is dripped, after the dripping is finished, the reaction is continued for 40min, and then a small amount of water is added for quenching, and the compound 1 is obtained through separation and purification. 50g of the compound 1 is dissolved in 120g of an ethanol aqueous solution, 196g of a 40% sodium hydroxide solution and 86g of chloroform are added thereto, the mixture is heated to 60 ℃ and reacted for 8 hours under the conditions, and the compound 2 is obtained by separation and purification. Dissolving 40g of the compound 2 in 200g of water, dropwise adding a small amount of 30% dilute sulfuric acid into the water until the pH value is 1.5, stirring the solution at 30 ℃ for 60min to separate out gray oily liquid, adding a certain amount of butyl acetate into the oily liquid to extract the oily liquid, and performing rotary evaporation and purification to obtain the vanillin product. The yield of vanillin (calculated by guaiacol) in the whole reaction process is about 89.73 percent.
[ example 4 ] A method for producing a polycarbonate
To a three-necked flask equipped with a thermometer, 48.3g of 2-methoxypyridine and 300g of N, N-Dimethylformamide (DMF) were added, and 48g of 98% sulfuric acid was slowly added dropwise to the reaction system at 5 ℃ to obtain a pyridinesulfonic acid complex whose elemental analysis was as follows: 37.89% of C, 4.24% of H, 7.36% of N, 33.65% of O and 16.86% of S. Then, 50g of guaiacol is dripped, reaction is continued for 60min after the dripping is finished, a small amount of water is added for quenching, and the compound 1 is obtained through separation and purification. 50g of the compound 1 was dissolved in 120g of an aqueous ethanol solution, and 171.5g of a 40% sodium hydroxide solution and 114.6g of chloroform were added thereto, heated to 80 ℃ and reacted for 10 hours under the conditions, and separated and purified to obtain a compound 2. Dissolving 40g of the compound 2 in 200g of water, dropwise adding a small amount of 30% dilute sulfuric acid into the water until the pH value is 2.0, stirring the solution at 80 ℃ for 10min to separate out gray oily liquid, adding a certain amount of butyl acetate into the oily liquid to extract the oily liquid, and performing rotary evaporation and purification to obtain a vanillin product. The yield of vanillin (calculated by guaiacol) in the whole reaction process is about 94.51%.
[ example 5 ]
48.3g of 3-methoxypyridine and 300g of tetrahydrofuran were added to a three-necked flask with a thermometer, and 60g of 98% concentrated sulfuric acid was slowly dropped into the reaction system at 10 ℃ to obtain a pyridine sulfonic acid complex, which was analyzed as follows: 37.89% of C, 4.24% of H, 7.36% of N, 33.65% of O and 16.86% of S. Then, 50g of guaiacol is dripped, after the dripping is finished, the reaction is continued for 80min, and then a small amount of water is added for extraction and extinction, and the compound 1 is obtained after separation and purification. 50g of the compound 1 is dissolved in 120g of ethanol aqueous solution, 180g of 40% sodium hydroxide solution and 177.3g of chloroform are added to the ethanol aqueous solution, the mixture is heated to 70 ℃, and the reaction is carried out for 5 hours under the condition, so that the compound 2 is obtained by separation and purification. Dissolving 40g of the compound 2 in 200g of water, dropwise adding a small amount of 30% dilute sulfuric acid into the water until the pH value is 2.5, stirring the solution at 40 ℃ for 35min to separate out gray oily liquid, adding a certain amount of butyl acetate into the oily liquid to extract the oily liquid, and performing rotary evaporation and purification to obtain the vanillin product. The yield of vanillin (calculated by guaiacol) in the whole reaction process is about 93.14%.
[ example 6 ]
82.1g of 2, 3-dimethoxypyridine and 300g of toluene are added into a three-necked flask with a thermometer, and 48g of 98% concentrated sulfuric acid is slowly added into the reaction system under the ice bath condition of 0 ℃ to obtain a pyridine sulfonic acid complex which has the following elemental analysis: 38.18 percent of C, 4.58 percent of H, 6.36 percent of N, 36.33 percent of O and 14.56 percent of S. Then, 50g of guaiacol is dripped, reaction is continued for 1 hour after the addition of guaiacol is finished, a small amount of water is added for quenching, and the compound 1 is obtained after separation and purification. 50g of the compound 1 is dissolved in 120g of ethanol aqueous solution, 265g of potassium carbonate and 296g of iodoform are added thereto, the mixture is heated to 120 ℃, and the mixture reacts for 24 hours under the condition, and the compound 2 is obtained through separation and purification. Dissolving 40g of the compound 2 in 200g of water, dropwise adding a small amount of 30% dilute sulfuric acid into the water until the pH value is 2.0, stirring the solution at 50 ℃ for 30min to separate out gray oily liquid, adding a certain amount of butyl acetate into the oily liquid to extract the oily liquid, and performing rotary evaporation and purification to obtain the vanillin product. The yield of vanillin (calculated by guaiacol) in the whole reaction process is about 90.85%.
Comparative example 1
To a three-necked flask with a thermometer, 50g of guaiacol, 300g of ethanol, 60g of sodium hydroxide solution and 0.2g of tetrabutylammonium bromide were added and the temperature was raised to 80 ℃. Under the condition of reflux and stirring, slowly dripping 40ml of trichloromethane into the reaction bottle, finishing dripping within 1h, and then reacting for 1.5h under the condition of slight boiling. After the temperature is reduced, 1mol/L hydrochloric acid is slowly dropped into the reaction liquid to be neutral, sodium chloride is removed by filtration, and the residue is fully washed by ethanol. White solid can be obtained after rotary evaporation and recrystallization of the filtrate, and the elemental analysis is as follows: c63.15%, H5.30%, O31.55%; the nuclear magnetic results were as follows: 1 H NMR(600MHz,CDCl 3 ): δ 3.86 (3H), 5.38 (1H), 7.27 (2H), 7.38 (1H), 9.61 (1H). The yield of vanillin (calculated by guaiacol) in the whole reaction process is about 40.28%.
Comparative example 2
To a three-necked flask with a thermometer, 50g of guaiacol, 300g of ethanol, 60g of sodium hydroxide solution and 10ml of triethylamine were added, and the temperature was raised to 80 ℃. Under the condition of reflux and stirring, slowly dripping 40ml of trichloromethane into the reaction bottle, finishing dripping within 1 hour, and then reacting for 1.5 hours under the condition of slight boiling. After cooling, 1mol/L hydrochloric acid is slowly dropped into the reaction liquid to be neutral, sodium chloride is removed by filtration, and the residue is fully washed by ethanol. Then distilling the filtrate under water vapor, distilling to remove triethylamine, then carrying out rotary evaporation and recrystallization to obtain a white solid, wherein the elemental analysis is as follows: c63.15%, H5.30%, O31.55%; the nuclear magnetic results were as follows: 1 H NMR(600MHz,CDCl 3 ): δ 3.83 (3H), 5.35 (1H), 7.25 (2H), 7.38 (1H), 9.61 (1H). The yield of vanillin (calculated by guaiacol) in the whole reaction process is about 75.77%.
The above description is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, several modifications and additions can be made without departing from the method of the present invention, and these modifications and additions should also be regarded as the protection scope of the present invention.
Claims (17)
1. A high-yield vanillin synthesis process is characterized by comprising the following steps:
1) Mixing guaiacol, alkyl pyridine and sulfonating agent to prepare a product 1; the step 1) is to mix the raw materials and react at the temperature of minus 10 to 10 ℃ for 15 to 80min; the sulfonating agent is fuming sulfuric acid or a sulfuric acid solution with the mass fraction of 50-98%;
2) Adding the product 1 and inorganic base into a reactor, dropwise adding a formylation reagent, and reacting to obtain a product 2;
3) Dissolving the product 2 in a solvent, adding acid, heating, stirring, cooling and purifying to obtain a target product vanillin;
the structural expression of the reaction process is as follows:
the structural expression of the alkyl pyridine in the step 1) is as follows:
wherein R is 1 、R 2 Respectively represent alkyl or alkoxy with carbon number of 0-1;
the formylation reagent in the step 2) is at least one of trichloromethane, tribromomethane and iodomethane.
2. The process for synthesizing vanillin with high yield according to claim 1, wherein the molar ratio of the guaiacol, the alkyl pyridine and the sulfonating agent in the step 1) is 1 (0.5-2): (0.5-2).
3. The process for synthesizing vanillin with high yield according to claim 2, wherein the molar ratio of the guaiacol, the alkyl pyridine and the sulfonating agent in the step 1) is 1 (1-1.6): (1-1.5).
4. A process for synthesizing vanillin with high yield according to any one of claims 1 to 3, wherein the raw materials in step 1) are mixed and then reacted in ice bath at 0 ℃ for 40-60 min.
5. The process of claim 4, wherein the alkyl pyridine is at least one of pyridine, 2-methylpyridine, 3-methylpyridine, 2-methoxypyridine, 3-methoxypyridine, and 2, 3-dimethoxypyridine;
the sulfonating agent in the step 1) is 98% concentrated sulfuric acid;
the method comprises the following step 1) and is characterized in that a reaction solvent is also added, wherein the reaction solvent is at least one of toluene, ethylbenzene, tetrahydrofuran, DMF and diethyl ether.
6. The process for synthesizing vanillin with high yield according to claim 5, wherein the reaction solvent in the step 1) is one or two of toluene and tetrahydrofuran.
7. The high-yield vanillin synthesis process according to claim 1, wherein the molar ratio of the product 1, the inorganic base and the formylation reagent in the step 2) is 1:7 to 9:2.5 to 4.
8. The high-yield vanillin synthesis process according to claim 7, wherein the molar ratio of the product 1, the inorganic base and the formylation reagent in the step 2) is 1.
9. The process for synthesizing vanillin with high yield according to claim 1 or 7, wherein the reaction temperature in the step 2) is 50-120 ℃ and the reaction time is 5-24 h.
10. The process for synthesizing vanillin with high yield according to claim 9, wherein the reaction temperature in the step 2) is 60-80 ℃ and the reaction time is 8-12 h.
11. The high-yield vanillin synthesis process according to claim 9, wherein the inorganic base in the step 2) is one or a mixture of any two of sodium hydroxide, potassium hydroxide, calcium hydroxide, potassium carbonate and sodium carbonate;
the formylation reagent in the step 2) is trichloromethane;
a reaction solvent is also added in the step 2), and the reaction solvent is at least one of methanol, ethanol, isopropanol and water.
12. The process for synthesizing vanillin with high yield according to claim 11, wherein the inorganic base in the step 2) is sodium hydroxide;
the reaction solvent in the step 2) is methanol water or ethanol water solution.
13. The process for synthesizing vanillin with high yield according to claim 1, wherein the addition amount of the acid in the step 3) is adjusted and controlled by pH, and the pH of the reaction system is 1.5-2.5.
14. The process for synthesizing vanillin with high yield according to claim 1 or 13, wherein the reaction temperature in the step 3) is 30-80 ℃ and the reaction time is 10-60 min.
15. The process for synthesizing vanillin with high yield according to claim 14, wherein the reaction temperature in the step 3) is 30-50 ℃ and the reaction time is 30-40 min.
16. The process for synthesizing vanillin with high yield according to claim 14, wherein the solvent in the step 3) is at least one of water, ethanol, DMF and methanol;
the acid in the step 3) is dilute hydrochloric acid, dilute sulfuric acid or dilute nitric acid.
17. The process for synthesizing vanillin with high yield according to claim 16, wherein the solvent in the step 3) is water;
the acid in the step 3) is dilute sulfuric acid.
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