Process for synthesis of vanillin by glyoxylic acid method

Abstract

The present application relates to the technical fields of organic chemical synthesis, in particular to a method for synthesizing vanillin by glyoxylic acid method, specifically, taking guaiacol and glyoxylic acid as raw materials, taking molybdenum salt and cobalt salt as a complex metal salt as a catalyst, using step-by-step reaction, first forming guaiacol sodium salt, then reacting with glyoxylic acid, and finally obtaining vanillin. The present application solves the technical problem of low yield of vanillin caused by many by-products of vanillin in the existing process of synthesizing vanillin by glyoxylic acid method.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organic chemical synthesis, in particular to a method for synthesizing vanillin by glyoxylic acid method. BACKGROUND

[0002] Vanillin is a precious broad-spectrum high-grade perfume, which is loved by perfumers because of its soft and elegant aroma, and is used as a fixative, a flavoring agent, and a flavoring agent. It is widely used in food, cakes, beverages and cosmetics, and also used in tobacco essence. It is an important raw material and intermediate in medicine synthesis.

[0003] The current mainstream production process is to synthesize vanillin by glyoxylic acid method. The main process is to condense guaiacol and glyoxylic acid to generate 3-methoxy-4-hydroxy mandelic acid, then oxidize to obtain 3-methoxy-4-hydroxy phenylacetic acid, and then acidize and decarboxylate to obtain vanillin crude product. After extraction, rectification, recrystallization, centrifugation and drying, vanillin product is obtained. This method will have side reactions when guaiacol and glyoxylic acid are condensed to generate 3-methoxy-4-hydroxy mandelic acid. Ortho-vanillin and bis-vanillin are generated, which affects the yield and purity of the synthesized vanillin, and is an important limiting factor for the industrial production of vanillin synthesized by glyoxylic acid method.

[0004] In view of the above problems, the prior art such as Chinese patent with publication number CN110483275A provides a high selectivity synthesis method of 3-methoxy-4-hydroxy mandelic acid. By using amphoteric metal salt as catalyst, the selectivity of 3-methoxy-4-hydroxy mandelic acid is improved in the condensation reaction, and the selectivity of the ortho-bis-condensation by-product is reduced, thereby finally improving the selectivity and yield of vanillin in the whole process. However, the above prior art still has the following problems: 1. The proportion of ortho-vanillin and bis-vanillin in the synthesized product is still more than 6%, of which the content of bis-vanillin is more than 2%, which affects the quality of vanillin; 2. The condensation reaction time is long, and even needs to react for 72 hours, which affects the efficiency of vanillin industrial production. SUMMARY

[0005] The present application aims to provide a method for synthesizing vanillin by glyoxylic acid method, in order to solve the technical problem of low yield of vanillin caused by many by-products in the prior art of synthesizing vanillin by glyoxylic acid method.

[0006] In order to achieve the above-mentioned purpose, the technical scheme adopted by the present application is as follows: a method for synthesizing vanillin by glyoxylic acid method, comprising the following steps:

[0007] S1: uniformly mixing guaiacol, molybdenum salt and cobalt salt, then adding sodium hydroxide aqueous solution dropwise, and uniformly mixing to obtain a mixed solution of guaiacol sodium salt and catalyst;

[0008] S2: add glyoxylic acid to the mixed solution in S1, mix well, then add sodium hydroxide aqueous solution dropwise to adjust the pH to alkaline, then control the temperature to carry out condensation reaction;

[0009] S3: after the completion of the condensation reaction, the reaction solution is transferred to a carbonylation reactor, heated to a certain temperature, then oxygen is introduced under stirring, after the reaction is completed, sulfuric acid solution is added to adjust the pH to acidic, then decarboxylation is carried out, after the completion of the decarboxylation reaction, extraction is carried out for multiple times to obtain vanillin.

[0010] The principle and advantages of the present scheme are:

[0011] The use of glyoxylic acid method to synthesize vanillin is a relatively mature industrial process for synthesizing vanillin at present, but it has always had the problem of low yield and purity of the product due to many side reactions. The researchers found that the main side reactions come from the condensation reaction, the nucleophilic addition reaction of the phenolic hydroxyl group ortho-carbon atom on the benzene ring of guaiacol with the carbonyl group of glyoxylic acid, generating 3-methoxy-2-hydroxy mandelic acid and 2-methoxy-4,6-bisacetic acid phenol (bis-mandelic acid). These side reaction intermediates, like 3-methoxy-4-hydroxy mandelic acid generated by the nucleophilic addition reaction of the phenolic hydroxyl group para-carbon atom on the benzene ring of guaiacol with the carbonyl group of glyoxylic acid, undergo oxidation and decarboxylation reactions to generate ortho-vanillin and bis-vanillin, respectively, which are the main side reaction products in the synthesis of vanillin, resulting in low yield and purity of the product. Moreover, ortho-vanillin and bis-vanillin have many similarities in physicochemical properties with vanillin, and it is very difficult to separate and purify them after the completion of the synthesis reaction, which greatly affects the industrial production of vanillin.

[0012] The present inventors found in practical work that most of the existing research on the synthesis of vanillin focuses on the selection and use of new catalysts, and the use of new catalysts to change the selectivity of guaiacol reaction, such as amphoteric metal catalysts or Y-type molecular sieve supported metal salt catalysts. Although the above new catalysts can improve the selectivity of vanillin synthesis to some extent, they are not suitable for industrial production. The main reason is that the synthesis process of such new catalysts is not mature enough, and the synthesis technology is relatively high, which is not suitable for large-scale production.

[0013] In view of the above problems, the present inventors use relatively mature chemicals such as cobalt salt and molybdenum salt as catalysts for condensation reaction, solving the problem of unstable source of catalysts. At the same time, the present inventors found in practical work that the use of cobalt salt and molybdenum salt in a certain ratio has a synergistic effect, which can further inhibit the generation of ortho-vanillin and bis-vanillin, and improve the synthesis yield and purity of vanillin. The principle can be explained as follows: 1) Co 2+ and Mo 3+The electron cloud distribution of guaiacol is changed by affecting the ortho position of phenolic hydroxyl group, thereby affecting the selectivity of the target product, and making it select the reaction in a single direction; 2) Co 2+ and Mo 3+ The hydrogen atoms at the ortho and para positions of the phenolic hydroxyl group of guaiacol interact at the same time, inhibit the further reaction of 3-methoxy-4-hydroxy mandelic acid and 2-hydroxy-3-methoxy mandelic acid with glyoxylic acid, thereby improving the selectivity of the target product; 3) Co 2+ and Mo 3+ Complexes or chelates are formed with guaiacol, thereby affecting the selectivity of the product.

[0014] Further, the molybdenum salt in S1 includes molybdenum chloride, molybdenum sulfate, and the cobalt salt includes cobalt chloride, cobalt sulfate, and cobalt nitrate.

[0015] In this application, common molybdenum salts and cobalt salts are selected as catalysts to ensure that the raw materials of the catalysts are easy to obtain and stable, and to reduce the cost of large-scale production.

[0016] Further, the molar ratio of the addition amount of the molybdenum salt and the cobalt salt in S1 is 1:0.5-1.5.

[0017] In this application, the ratio of molybdenum salt and cobalt salt will affect the catalytic effect. If the content of molybdenum salt is too high, if the content of cobalt salt is too high.

[0018] Further, the mass concentration of the sodium hydroxide solution in S1 is 28-32%.

[0019] In this application, the use of saturated sodium hydroxide solution can ensure the formation of guaiacol sodium salt with high concentration with guaiacol, and accelerate the reaction rate. At the same time, the use of saturated sodium hydroxide is more conducive to adjusting the pH value of the reaction.

[0020] Further, the molar ratio of the catalyst to guaiacol in S1 is 4-6:100.

[0021] In this application, if the amount of catalyst added is small, it cannot inhibit the side reaction, and if the amount of catalyst added is large, the inhibition effect on the side reaction is not significantly improved.

[0022] Further, the mass concentration of the guaiacol sodium salt solution in the mixed solution in S1 is 8-14%.

[0023] In this application, keeping the concentration of guaiacol sodium salt solution within a reasonable range can improve the condensation reaction speed. If the concentration of guaiacol sodium salt solution is too high, crystals will be precipitated, making the reaction change from a homogeneous reaction to a heterogeneous reaction, which will increase the reaction time and cause a large number of glyoxylic acid anions to exist, resulting in side reactions.

[0024] Further, the molar ratio of guaiacol to glyoxylic acid in S2 is 1.1-1.5:1.

[0025] In the present application, the content of guaiacol in the reaction needs to be more than that of glyoxylic acid to reduce the occurrence of side reactions. Too much guaiacol will cause waste of raw materials.

[0026] Further, the condensation reaction temperature in S2 is 30-50℃.

[0027] In the present application, a lower reaction temperature will affect the reaction, resulting in a lower yield of vanillin. A higher reaction temperature will cause side reactions to occur, resulting in a larger amount of by-products, ortho-vanillin and bis-vanillin.

[0028] Further, in S2, sodium hydroxide is added dropwise to a pH value of 11-12.

[0029] In the present application, the reaction of guaiacol and glyoxylic acid needs to be kept in an alkaline condition.

[0030] Further, in S3, the heating temperature is raised to 100℃, the oxygen is introduced for 60-90min, and the decarboxylation reaction is carried out at a pH value of 2-3.

[0031] In the present application, the condensation reaction temperature is kept at about 100℃ to ensure the smooth progress of the reaction and improve the efficiency of the condensation reaction. The oxidation time is controlled within 2 hours to complete most of the reaction conversion. Compared with the reaction time of several tens of hours in the prior art, the present application shortens the production cycle and reduces energy consumption. The decarboxylation reaction needs to be carried out in a strong acid environment. BRIEF DESCRIPTION OF DRAWINGS

[0032] Figure 1 The high-performance liquid chromatogram of the reaction product in Example 1 of the present application. DETAILED DESCRIPTION

[0033] The following will be further described in detail through specific embodiments:

[0034] Example 1

[0035] A method for synthesizing vanillin by glyoxylic acid method, comprising the following steps:

[0036] S1: First, mix guaiacol, molybdenum salt and cobalt salt uniformly, then add dropwise sodium hydroxide aqueous solution to the mixture, and mix uniformly to obtain a mixed solution of guaiacol sodium salt and catalyst;

[0037] Specifically, 1.4 mol of guaiacol, 0.028 mol of molybdenum chloride and cobalt chloride were taken, wherein the molar ratio of molybdenum chloride to cobalt chloride was 1:1. The mixture was mixed uniformly, and a saturated sodium hydroxide solution was taken and slowly added dropwise to the mixture of guaiacol, molybdenum chloride and cobalt chloride, while stirring. When the mass concentration of guaiacol sodium salt was 11%, the dropwise addition was stopped and the stirring was continued.

[0038] S2: Add glyoxylic acid to the mixed solution in S1, mix uniformly, then add an aqueous sodium hydroxide solution dropwise to adjust the pH to alkaline, and then control the temperature to carry out the condensation reaction;

[0039] Specifically, glyoxylic acid was added dropwise to the mixed solution in S1, and the total amount of glyoxylic acid added was 1 mol. After the addition of glyoxylic acid was completed, a saturated sodium hydroxide solution was added dropwise to the mixture until the pH value reached 11. After the dropwise addition of sodium hydroxide was completed, the mixture was stirred uniformly, and then the reaction temperature was increased to 40°C, and the reaction was carried out at this temperature for 3 hours.

[0040] S3: After the completion of the condensation reaction, the reaction solution was transferred to a carbonylation reactor, heated to a certain temperature, and then oxygen was introduced into the reactor under stirring conditions. After the reaction was completed, sulfuric acid solution was added to the reactor to adjust the pH to acidic, and then decarboxylation reaction was carried out. After the completion of the decarboxylation reaction, the reaction solution was extracted several times to obtain vanillin.

[0041] Specifically, after the completion of the condensation reaction, the reaction solution was transferred to a carbonylation reactor, heated to 100°C, and then oxygen was introduced into the reactor under stirring conditions for 60 minutes. After the reaction was completed, sulfuric acid solution was added to the reactor to adjust the pH of the solution to 3 for decarboxylation reaction. The decarboxylation reaction time was 30 minutes. After the completion of the reaction, the reaction solution was extracted with toluene at least 3 times. The organic phase was recovered, and vanillin was collected by distillation. The overall yield of vanillin was calculated, and the component content of vanillin, ortho-vanillin and bis-vanillin in the product was analyzed. The experimental results are recorded in Table 1 below.

[0042] Example 2

[0043] The difference between this example and Example 1 is that the molar ratio of catalyst to guaiacol in S1 is 6:100.

[0044] Example 3

[0045] The difference between this example and Example 1 is that the mass concentration of guaiacol sodium salt in S1 is 8%.

[0046] Example 4

[0047] The difference between this example and Example 1 is that the condensation reaction temperature in S2 is 50°C.

[0048] Example 5

[0049] The difference between this example and Example 1 is that the molar ratio of molybdenum chloride and cobalt chloride in S1 is 1:1.5.

[0050] Example 6

[0051] The difference between this example and Example 1 is that the molar ratio of molybdenum chloride and cobalt chloride in S1 is 1:0.5.

[0052] Comparative Example 1

[0053] The difference between this comparative example and Example 1 is that only molybdenum chloride is used as the catalyst in S1.

[0054] Comparative Example 2

[0055] The difference between this comparative example and Example 1 is that only cobalt chloride is used as the catalyst in S1.

[0056] Comparative Example 3

[0057] The difference between this comparative example and Example 1 is that the mass concentration of guaiacol sodium salt in S1 is 4%.

[0058] Comparative Example 4

[0059] The difference between this comparative example and Example 1 is that the molar ratio of catalyst to guaiacol in S1 is 10:100.

[0060] Comparative Example 5

[0061] The difference between this comparative example and Example 1 is that the condensation reaction temperature in S2 is 20°C.

[0062] Comparative Example 6

[0063] The difference between this comparative example and Example 1 is that the reaction steps are different, specifically:

[0064] Take 1.4 mol of guaiacol, 0.028 mol of molybdenum chloride and cobalt chloride, and the molar ratio of molybdenum chloride to cobalt chloride is 1:1. Add a total of 1 mol of glyoxylic acid, mix well, and then add saturated sodium hydroxide solution to pH 11. After the sodium hydroxide is added dropwise, stir well, then increase the reaction temperature to 40°C for condensation reaction, and keep the temperature constant for h. After the condensation reaction is completed, transfer the reaction liquid to a carbonylation reactor, heat to 100°C, and then pass in under stirring for 60 minutes. After the reaction is completed, add sulfuric acid solution to the reactor to adjust the solution pH to 3 for decarboxylation. The decarboxylation reaction time is h, and after the reaction is completed, extract the reaction solution with toluene at least 3 times, recover the organic phase, and distill to recover vanillin.

[0065] Table 1: Experimental conditions and experimental results data table of experimental examples and comparative examples

[0066] Table 1: Experimental conditions and experimental results data table of experimental examples and comparative examples

[0067]

[0068] Analysis of experimental results: In Table 1, the peak areas of vanillin, ortho-vanillin, and para-vanillin represent the areas of the corresponding peaks in high performance liquid chromatography.

[0069] Comparative Examples 1 and 2 used only molybdenum and cobalt salts as catalysts, respectively. With the addition amount remaining constant, the yield of vanillin showed a significant decrease. Furthermore, the peak areas showed that when only one metal salt was used as a catalyst, the peak areas of ortho-vanillin and para-vanillin were significantly increased compared to Example 1, indicating an increase in byproducts.

[0070] In Comparative Example 3, the concentration of sodium guaiacol was relatively low, and the experimental results showed that the yield of the reaction product was significantly reduced. The main reason for this is that when the concentration of sodium guaiacol is too low, it affects the reaction rate, and a large amount of guaiacol and glyoxylic acid remain unreacted during the reaction.

[0071] In Comparative Example 4, the amount of catalyst used was increased, but the results showed that it did not significantly improve the side effect. In fact, the excessive amount of catalyst led to an increase in side reactions.

[0072] In Comparative Example 5, the condensation reaction temperature was lowered. The results show that a condensation reaction temperature that is too low will affect the yield of vanillin.

[0073] Comparative Example 6 changed the reaction steps and adopted a one-pot reaction method. The results showed that the distribution reaction can effectively improve the product yield.

[0074] The above descriptions are merely embodiments of the present invention, and common knowledge such as specific technical solutions and / or characteristics are not described in detail here. It should be noted that those skilled in the art can make various modifications and improvements without departing from the technical solutions of the present invention, and these should also be considered within the scope of protection of the present invention. These modifications and improvements will not affect the effectiveness of the implementation of the present invention or the practicality of the patent. The scope of protection claimed in this application should be determined by the content of its claims, and the specific embodiments described in the specification can be used to interpret the content of the claims.

Claims

1. A method for synthesizing vanillin via glyoxylic acid, characterized in that: Includes the following steps: S1: Mix guaiacol, molybdenum salt and cobalt salt evenly, then add sodium hydroxide aqueous solution dropwise, and mix and react evenly to obtain a mixed solution of sodium guaiacol salt solution and catalyst; the molar ratio of added molybdenum salt and cobalt salt is 1:0.5~1.5; molybdenum salt and cobalt salt are catalysts; the molar ratio of catalyst to guaiacol is 4~6:100; S2: Add glyoxylic acid to the mixed solution in S1, mix well, and then add sodium hydroxide aqueous solution dropwise to adjust the pH to 11-12. Then control the temperature at 30-50℃ to carry out the condensation reaction; the molar ratio of guaiacol to glyoxylic acid is 1.1-1.5:

1. S3: After the condensation reaction is completed, the reaction solution is transferred to the carbonylation reactor, heated to a certain temperature, and oxygen is introduced under stirring to react. After the reaction is completed, sulfuric acid solution is added to the reactor to adjust the pH to acidic and then decarboxylation is carried out. After the decarboxylation reaction is completed, extraction is performed multiple times to obtain vanillin.

2. The method for synthesizing vanillin via glyoxylic acid as described in claim 1, characterized in that: The molybdenum salt in S1 includes molybdenum chloride and molybdenum sulfate, and the cobalt salt includes cobalt chloride, cobalt sulfate, and cobalt nitrate.

3. The method for synthesizing vanillin via glyoxylic acid according to claim 2, characterized in that: The sodium hydroxide solution in S1 has a mass concentration of 28-32%.

4. The method for synthesizing vanillin via glyoxylic acid according to claim 3, characterized in that: The mass concentration of sodium guaiacol salt solution in the mixed solution in S1 is 8-14%.

5. The method for synthesizing vanillin via glyoxylic acid according to claim 4, characterized in that: The temperature in S3 is raised to 100°C, oxygen is introduced into S3 and the reaction time is 60-90 min, and the pH value of the decarboxylation reaction in S3 is 2-3.

Images