A kind of synthetic method of 4-acetoxy-2-methylbutyraldehyde

Abstract

The invention discloses a method for synthesizing 4-acetoxy-2-methylbutyraldehyde. 4-hydroxy-2-butanone is used as a starting raw material, and condensation, hydrolysis, and esterification (or esterification, condensation, and hydrolysis) reactions are performed to prepare the 4-acetoxy-2-methylbutyraldehyde. The condensation is performed under the catalytic action of an alkaline substance and a halogenated acetate is used as one of the reaction raw materials. The esterification uses acetic acid and / or acetic anhydride as one of the reaction raw materials. The reaction process is highly safe and easy to operate, and the yield is high. In particular, the raw materials are simple and readily available, and no noble metal catalyst is required in the reaction process, thereby significantly reducing the preparation cost. Compared with the prior art, the method is more suitable for large-scale industrial production.

Description

Technical Field

[0001] The present invention relates to the technical field of fine chemicals, and in particular to a method for synthesizing 4-acetoxy-2-methylbutanal. Background Art

[0002] Vitamin E, vitamin A and carotenoids are important nutrients in animals and humans. 4-acetoxy-2-methylbutanal is one of the important intermediate structural units for the synthesis of these substances. The structure of 4-acetoxy-2-methylbutanal is as follows:

[0003]

[0004] The existing technology mainly obtains 4-acetoxy-2-methylbutanal by hydrogenation. For example, CN103328431A discloses a method for preparing 4-acetoxy-2-methylbutanal by catalytic hydrogenation of carbon-carbon double bonds. The method uses 4-acetoxy-2-methylbutanal as a raw material and catalytically hydrogenates it under a non-acidic catalyst system to prepare 4-acetoxy-2-methylbutanal.

[0005] However, in this catalytic hydrogenation method, not only is it difficult to obtain the raw material 4-acetoxy-2-methylbutenal (for example, CN112920047A involves a hydroformylation reaction with high safety risks, using precious metal catalysts such as rhodium or cobalt), but it also requires the use of a precious metal catalyst, Pd-based catalyst, resulting in high preparation costs. In particular, the hydrogenation reaction process has high safety risks, which is not conducive to practical application. Summary of the Invention

[0006] The object of the present invention is to overcome one or more deficiencies in the prior art and provide a new method for preparing 4-acetoxy-2-methylbutanal. The method not only uses simple and readily available raw materials, but also eliminates the need for expensive precious metal catalysts during the reaction, thereby significantly reducing costs. The method also provides a safer reaction process, avoids high-risk processes such as hydrogenation, and simultaneously achieves a higher reaction yield.

[0007] In order to achieve the above object, the technical solution adopted by the present invention is:

[0008] A method for synthesizing 4-acetoxy-2-methylbutanal, wherein 4-hydroxy-2-butanone is used as a raw material and processed by steps (i) and (ii) to produce 4-acetoxy-2-methylbutanal;

[0009] Wherein, step (i) comprises: subjecting a first reaction material to a condensation reaction under the catalytic action of an alkaline substance, followed by hydrolysis, wherein the first reaction material comprises a halogenated acetate;

[0010] Step (ii) comprises: subjecting a second reaction material to an esterification reaction, wherein the second reaction material comprises acetic acid and / or acetic anhydride;

[0011] When the steps (i) and (ii) are carried out in this order, 4-hydroxy-2-butanone is subjected to a condensation reaction with the halogenated acetic acid ester of step (i), followed by hydrolysis, and the resulting 4-hydroxy-2-methylbutanal is subjected to an esterification reaction with acetic acid and / or acetic anhydride of step (ii) to produce 4-acetoxy-2-methylbutanal.

[0012] When the steps (ii) and (i) are carried out in this order, 4-hydroxy-2-butanone is subjected to an esterification reaction with acetic acid and / or acetic anhydride in step (ii), and the resulting 4-acetoxy-2-butanone is subjected to a condensation reaction with the halogenated acetate in step (i), followed by hydrolysis to produce 4-acetoxy-2-methylbutanal.

[0013] In the present invention, when the steps (i) and (ii) are carried out in this order, the reaction process is shown as follows:

[0014]

[0015] When the steps (ii) and (i) are carried out in this order, the reaction process is shown as follows:

[0016]

[0017] X is a halogen, such as chlorine or bromine; R is a methyl or ethyl group.

[0018] Furthermore, the present invention innovatively uses 4-hydroxy-2-butanone as a starting material. When the steps (i) and (ii) are carried out in sequence, the halogenated acetate forms a carbon anion under the action of an alkaline substance, and then undergoes nucleophilic addition with 4-hydroxy-2-butanone, followed by intramolecular nucleophilic substitution, and the halogen X leaves to generate an epoxy carboxylate A. After hydrolysis, 4-hydroxy-2-methylbutanal can be obtained, and then esterification can give 4-acetoxy-2-methylbutanal;

[0019] When the steps (ii) and (i) are carried out in this order, 4-hydroxy-2-butanone is esterified with acetic acid and / or acetic anhydride to form 4-acetoxy-2-butanone. When condensation is carried out, similarly, the halogenated acetate forms a carbon anion under the action of an alkaline substance, and then undergoes nucleophilic addition with 4-acetoxy-2-butanone, followed by intramolecular nucleophilic substitution, and the halogen X leaves to form an epoxy carboxylate B. After hydrolysis, 4-acetoxy-2-methylbutanal can be obtained.

[0020] According to some preferred aspects of the present invention, the condensation reaction is carried out in an alcohol solvent. According to the present invention, compared with other solvents such as acetonitrile and benzene, alcohol solvents are more suitable for the system of the present invention.

[0021] Furthermore, the alcohol solvent is methanol and / or ethanol.

[0022] According to some preferred aspects of the present invention, the alkaline substance is sodium alkoxide.

[0023] Furthermore, the sodium alkoxide is a combination of one or more selected from sodium methoxide, sodium ethoxide and sodium tert-butoxide, and these bases are beneficial to the condensation reaction of the present invention.

[0024] According to some preferred and specific aspects of the present invention, the halogenated acetate is methyl chloroacetate and / or ethyl chloroacetate.

[0025] According to the present invention, the present invention can be carried out at a relatively low temperature; further, according to some preferred aspects of the present invention, the condensation reaction is carried out at a temperature of -50 to 30°C. If the reaction temperature is higher, the reaction yield will be reduced and more by-product polymers, waste materials, etc. will be produced.

[0026] Furthermore, the condensation reaction is carried out at a temperature of -30 to 0°C.

[0027] In some embodiments of the present invention, the reaction time of the condensation reaction is controlled to be 1-15 hours.

[0028] In some embodiments of the present invention, the reaction time of the condensation reaction is controlled to be 3-10 hours.

[0029] According to some preferred aspects of the present invention, the esterification reaction is carried out at a temperature of 30-100°C.

[0030] Furthermore, the esterification reaction is carried out at a temperature of 40-80°C.

[0031] In some embodiments of the present invention, the reaction time of the esterification reaction is controlled to be 1-30 hours.

[0032] In some embodiments of the present invention, the reaction time of the esterification reaction is controlled to be 2-15 hours.

[0033] In some embodiments of the present invention, when the steps (i) and (ii) are performed in this order, the molar ratio of the 4-hydroxy-2-butanone, the halogenated acetate and the alkaline substance is 1:1.1-1.5:1.1-2, and the molar ratio of the 4-hydroxy-2-methylbutanal to the acetic acid and / or acetic anhydride is 1:1-1.5.

[0034] According to some preferred aspects of the present invention, when the steps (i) and (ii) are carried out in this order, the hydrolysis agent used in the hydrolysis is water, and the hydrolysis temperature is 20-60°C.

[0035] In some embodiments of the present invention, when the steps (ii) and (i) are carried out in this order, the molar ratio of the 4-hydroxy-2-butanone to the acetic acid and / or acetic anhydride is 1:1-1.5, and the molar ratio of the 4-acetoxy-2-butanone to the halogenated acetate and the alkaline substance is 1:1.1-1.5:1.1-2.

[0036] According to some preferred aspects of the present invention, when the steps (ii) and (i) are performed sequentially, the hydrolysis agent used is dilute sulfuric acid having a mass percentage of less than or equal to 70%, and the hydrolysis temperature is 30-60°C. In the present invention, the use of dilute sulfuric acid as the hydrolysis agent can neutralize the residual alkali in the unreacted system, reduce the hydrolysis of the ester group formed after the initial esterification, and improve the yield of 4-acetoxy-2-methylbutanal when the steps (ii) and (i) are performed sequentially.

[0037] In some embodiments of the present invention, the mass percentage of the dilute sulfuric acid is 1%-30%, or 5%-20%.

[0038] According to some preferred and specific aspects of the present invention, when the steps (i) and (ii) are performed in sequence, the embodiment of preparing 4-acetoxy-2-methylbutanal includes: dissolving an alkaline substance in an alcohol solvent to obtain an alkaline solution, cooling the solution to a first temperature, mixing 4-hydroxy-2-butanone with the halogenated acetic acid ester of step (i) and cooling the solution to a second temperature, and then adding the mixture dropwise to the alkaline solution. After the addition is complete, the mixture is kept warm for reaction at a third temperature. After the addition is complete, water is added for hydrolysis to obtain 4-hydroxy-2-methylbutanal; and then preheating the 4-hydroxy-2-methylbutanal to a fourth temperature, adding acetic acid and / or acetic anhydride dropwise, and after the addition is complete, the mixture is kept warm for reaction at a fifth temperature to generate 4-acetoxy-2-methylbutanal.

[0039] According to some preferred and specific aspects of the present invention, when the steps (ii) and (i) are performed in this order, the method for preparing 4-acetoxy-2-methylbutanal includes: preheating acetic acid and / or acetic anhydride to a sixth temperature, adding 4-hydroxy-2-butanone dropwise, and then incubating the mixture at a seventh temperature to react to obtain 4-acetoxy-2-butanone; dissolving an alkaline substance in an alcohol solvent to obtain an alkaline solution, cooling the mixture to an eighth temperature, mixing 4-acetoxy-2-butanone with the halogenated acetate of step (i), cooling the mixture to a ninth temperature, and then adding the mixture dropwise to the alkaline solution, then incubating the mixture at a tenth temperature to react to obtain 4-acetoxy-2-methylbutanal. After the incubation is completed, dilute sulfuric acid having a mass percentage of 70% or less is added for hydrolysis to produce 4-acetoxy-2-methylbutanal.

[0040] According to some preferred aspects of the present invention, the first temperature, the second temperature, the third temperature, the eighth temperature, the ninth temperature and the tenth temperature are respectively -50 to 30°C; the fourth temperature, the fifth temperature, the sixth temperature and the seventh temperature are respectively 30 to 100°C.

[0041] Due to the application of the above technical solution, the present invention has the following advantages compared with the prior art:

[0042] Based on the problems existing in the preparation of 4-acetoxy-2-methylbutanal, such as the difficulty in obtaining reaction raw materials, the high cost of catalysts, and the high safety risks of the reaction process, the present invention innovatively proposes using 4-hydroxy-2-butanone as a starting raw material and carrying out condensation, hydrolysis, and esterification (or esterification, condensation, and hydrolysis) reactions. The reaction process is highly safe and easy to operate, and has a high yield. In particular, the raw materials are simple and readily available, and no precious metal catalyst is required in the reaction process, thereby significantly reducing the preparation cost. Compared with the existing technology, the present invention is more suitable for large-scale industrial production. DETAILED DESCRIPTION

[0043] The above scheme is further described below in conjunction with specific examples; it should be understood that these examples are used to illustrate the basic principles, main features and advantages of the present invention, and the present invention is not limited to the scope of the following examples; the implementation conditions adopted in the examples can be further adjusted according to specific requirements, and the implementation conditions not specified are generally the conditions in routine experiments.

[0044] Unless otherwise specified in the following examples, all raw materials were purchased from commercial sources or prepared by conventional methods in the art.

[0045] The yield calculation method in the embodiment is:

[0046] Yield of 4-hydroxy-2-methylbutanal to 4-hydroxy-2-butanone = [mass of 4-hydroxy-2-methylbutanal product × GC detection content] / [molar amount of 4-hydroxy-2-butanone added × molecular weight of 4-hydroxy-2-methylbutanal];

[0047] Yield of 4-acetoxy-2-methylbutanal to 4-hydroxy-2-methylbutanal = [mass of 4-acetoxy-2-methylbutanal product × GC detection content] / [mass of 4-hydroxy-2-methylbutanal added × GC detection content ÷ molecular weight of 4-hydroxy-2-methylbutanal × molecular weight of 4-acetoxy-2-methylbutanal];

[0048] Yield of 4-acetoxy-2-methylbutanal to 4-hydroxy-2-butanone = product of yield of 4-hydroxy-2-methylbutanal to 4-hydroxy-2-butanone × yield of 4-acetoxy-2-methylbutanal to 4-hydroxy-2-methylbutanal.

[0049] Example 1

[0050] This example provides a method for synthesizing 4-acetoxy-2-methylbutanal. The synthetic route is as follows:

[0051]

[0052] The synthesis method comprises:

[0053] (1) Synthesis of 4-hydroxy-2-methylbutyraldehyde

[0054] Dissolve 190.4g of sodium ethoxide (2.8mol) in 500mL of ethanol to obtain a sodium ethoxide solution, which is precooled to -10°C. Mix 4-hydroxy-2-butanone (176g, 2mol) and ethyl chloroacetate (294g, 2.4mol) and precool to 0°C, then add dropwise to the sodium ethoxide solution for a condensation reaction. Control the addition time for 8h. After the addition is complete, incubate at 0°C for 3h. After incubation, add 1000mL of water for hydrolysis at 55±5°C. After hydrolysis, add 500mL of dichloromethane for extraction and separate the water layer to obtain a dichloromethane solution of 4-hydroxy-2-methylbutanal. Dichloromethane was removed by atmospheric and vacuum distillation at 50±10°C, and then the absolute pressure was reduced to 1000 Pa. The product was distilled at 100±10°C to obtain 162.9 g of 4-hydroxy-2-methylbutanal. The GC content was 98.2%, and the yield was 78.4%.

[0055] (2) Synthesis of 4-acetoxy-2-methylbutyraldehyde

[0056] 103.9 g of 4-hydroxy-2-methylbutanal (GC content 98.2%) was preheated to 100°C. 112 g of acetic anhydride was then added dropwise over 6 hours, and the mixture was kept at 100°C for another 2 hours. After the reaction was complete, the pressure was reduced to 50 kPa absolute, and the acetic acid and acetic anhydride were recovered by distillation at 95±15°C to yield 144.9 g of 4-acetoxy-2-methylbutanal. The GC content was 97.8%, for a yield of 98.4%.

[0057] The molar yield of 4-acetoxy-2-methylbutanal to 4-hydroxy-2-butanone was 77.1%.

[0058] Example 2

[0059] This example provides a method for synthesizing 4-acetoxy-2-methylbutanal. The synthetic route is as follows:

[0060]

[0061] The synthesis method comprises:

[0062] (1) Synthesis of 4-hydroxy-2-methylbutyraldehyde

[0063] Dissolve 129.6g of sodium methoxide (2.4mol) in 500mL of methanol to obtain a sodium methoxide solution, which is precooled to -10°C. Mix 4-hydroxy-2-butanone (176g, 2mol) and methyl chloroacetate (238.7g, 2.2mol) and precool to -10°C, then add dropwise to the sodium methoxide solution for a condensation reaction. The addition time is controlled to 5h, and the reaction is kept at -10°C for 2h. After the incubation, 1000mL of water is added for hydrolysis at 25±5°C. After the hydrolysis, 500mL of n-hexane is added for extraction and the water layer is separated to obtain a n-hexane solution of 4-hydroxy-2-methylbutanal. The n-hexane was removed by vacuum distillation at 60±20°C, and then the absolute pressure was reduced to 1000 Pa. The product was distilled at 100±10°C to obtain 175.5 g of 4-hydroxy-2-methylbutanal. The GC detection content was 99.5%, and the yield was 85.6%.

[0064] (2) Synthesis of 4-acetoxy-2-methylbutyraldehyde

[0065] 102.5 g of 4-hydroxy-2-methylbutanal (GC content 99.5%) was preheated to 40°C. 122 g of acetic anhydride was then added dropwise over 4 hours, and the reaction was continued at 40°C for 20 hours. After the reaction was completed, the pressure was reduced to 50 kPa absolute, and the acetic acid and acetic anhydride were recovered by distillation at 95±15°C to obtain 144.6 g of 4-acetoxy-2-methylbutanal. The GC content was 99.2%, and the yield was 99.6%.

[0066] The molar yield of 4-acetoxy-2-methylbutanal to 4-hydroxy-2-butanone was 85.3%.

[0067] Example 3

[0068] This example provides a method for synthesizing 4-acetoxy-2-methylbutanal, which comprises:

[0069] (1) Synthesis of 4-hydroxy-2-methylbutyraldehyde

[0070] Dissolve 307.2g of sodium tert-butoxide (3.2mol) in 500mL of methanol to obtain a sodium tert-butoxide solution, which is pre-cooled to -30°C. Mix 4-hydroxy-2-butanone (176g, 2mol) and methyl chloroacetate (282.1g, 2.6mol) and pre-cool to -30°C, then add dropwise to the sodium tert-butoxide solution for a condensation reaction. The addition time is controlled to 6h, and the mixture is kept at -30°C for 4h. After the incubation, 1000mL of water is added for hydrolysis at 55±5°C. After the hydrolysis, 500mL of petroleum ether is added for extraction and the water layer is separated to obtain a petroleum ether solution of 4-hydroxy-2-methylbutanal. The petroleum ether was removed by vacuum distillation at 60±20°C, and then the absolute pressure was reduced to 1000 Pa. The product was distilled at 100±10°C to obtain 177.9 g of 4-hydroxy-2-methylbutanal. The GC detection content was 99.2%, and the yield was 86.5%.

[0071] (2) Synthesis of 4-acetoxy-2-methylbutyraldehyde

[0072] 102.8 g of 4-hydroxy-2-methylbutanal (GC content 99.2%) was preheated to 80°C. 132 g of acetic anhydride was then added dropwise over 8 hours, and the reaction was continued at 80°C for 4 hours. After the reaction was completed, the pressure was reduced to 40 kPa absolute, and the acetic acid and acetic anhydride were recovered by distillation at 90±20°C to obtain 144.6 g of 4-acetoxy-2-methylbutanal. The GC content was 99.3%, and the yield was 99.7%.

[0073] The molar yield of 4-acetoxy-2-methylbutanal to 4-hydroxy-2-butanone was 86.2%.

[0074] Example 4

[0075] This example provides a method for synthesizing 4-acetoxy-2-methylbutanal, which comprises:

[0076] (1) Synthesis of 4-hydroxy-2-methylbutyraldehyde

[0077] Dissolve 272g of sodium methoxide (4 mol) in 500mL of methanol to obtain a sodium methoxide solution, which is precooled to 10°C. Mix 4-hydroxy-2-butanone (176g, 2 mol) and methyl chloroacetate (325.5g, 3 mol) and precool to 10°C. Add the mixture dropwise to the sodium methoxide solution for a condensation reaction over a 12-hour period. Incubate the mixture at 10°C for 3 hours. After incubation, add 1000mL of water for hydrolysis at 45±5°C. After hydrolysis, add 500mL of toluene for extraction, and separate the water layer to obtain a toluene solution of 4-hydroxy-2-methylbutanal. Rectification under reduced pressure at 70±20°C to remove the toluene. Then, reduce the pressure to an absolute pressure of 1000 Pa and perform rectification at 100±10°C to obtain 159.4g of the 4-hydroxy-2-methylbutanal product. GC analysis shows a 97.5% content, resulting in a yield of 76.2%.

[0078] (2) Synthesis of 4-acetoxy-2-methylbutyraldehyde

[0079] 104.6 g of 4-hydroxy-2-methylbutanal (GC content 97.5%) was preheated to 30°C. 153 g of acetic anhydride was then added dropwise over 5 hours, and the reaction was continued at 40°C for 25 hours. After the reaction was completed, the pressure was reduced to 50 kPa absolute, and the acetic acid and acetic anhydride were recovered by distillation at 95±15°C to obtain 147.1 g of C54-acetoxy-2-methylbutanal. The GC content was 97.3%, and the yield was 99.4%.

[0080] The molar yield of 4-acetoxy-2-methylbutanal to 4-hydroxy-2-butanone was 75.7%.

[0081] Example 5

[0082] This example provides a method for synthesizing 4-acetoxy-2-methylbutanal. The synthetic route is as follows:

[0083]

[0084] The synthesis method comprises:

[0085] (1) Synthesis of 4-acetoxy-2-butanone

[0086] 214g of acetic anhydride was preheated to 100°C, followed by the dropwise addition of 176g of 4-hydroxy-2-butanone (2 mol). The addition was complete over 6 hours, and the reaction was continued at 100°C for 1 hour. After the reaction was completed, the pressure was reduced to 50kPa absolute, and the acetic acid and acetic anhydride were recovered by distillation at 90±10°C to obtain 259.7g of 4-acetoxy-2-butanone. The GC assay showed a content of 98.5%, for a yield of 98.4%.

[0087] (2) Synthesis of 4-acetoxy-2-methylbutyraldehyde

[0088] 100g of sodium ethoxide was dissolved in 500mL of ethanol to obtain a sodium ethoxide solution, which was precooled to -20°C. 200g of 4-acetoxy-2-butanone (GC content 98.5%) was mixed with 180g of ethyl chloroacetate and precooled to -20°C. The mixture was then added dropwise to the sodium ethoxide solution for a condensation reaction. The addition time was controlled to 8 hours, and the mixture was incubated at 0°C for 3 hours. After incubation, 5% dilute sulfuric acid was added for neutralization, and the mixture was then heated to 45±5°C for hydrolysis and decarboxylation. After hydrolysis, 400mL of dichloromethane was added for extraction, and the water layer was separated to obtain a dichloromethane solution of 4-acetoxy-2-methylbutanal. The dichloromethane was removed by atmospheric and vacuum distillation at 50±10°C, and the mixture was then reduced to an absolute pressure of 1000 Pa. The product, 184.1g, was obtained by distillation at 100±10°C. The GC content was 99.1%, and the yield was 83.6%.

[0089] The molar yield of 4-acetoxy-2-methylbutanal to 4-hydroxy-2-butanone was 82.3%.

[0090] Example 6

[0091] This example provides a method for synthesizing 4-acetoxy-2-methylbutanal. The synthetic route is as follows:

[0092]

[0093] The synthesis method comprises:

[0094] (1) Synthesis of 4-acetoxy-2-butanone

[0095] 245g of acetic anhydride was preheated to 80°C, followed by the dropwise addition of 176g of 4-hydroxy-2-butanone (2 mol). The addition was complete over 8 hours, and the reaction was continued at 80°C for 3 hours. After the reaction was completed, the pressure was reduced to 50kPa absolute, and the acetic acid and acetic anhydride were recovered by distillation at 90±10°C to obtain 259.5g of 4-acetoxy-2-butanone. The GC assay showed a content of 99.4%, for a yield of 99.2%.

[0096] (2) Synthesis of 4-acetoxy-2-methylbutyraldehyde

[0097] 145g of sodium methoxide was dissolved in 500mL of methanol to obtain a sodium methoxide solution, which was precooled to -30°C. 200g of 4-acetoxy-2-butanone (GC content 99.4%) was mixed with 225g of methyl chloroacetate and precooled to -30°C. The mixture was then added dropwise to the sodium methoxide solution for a condensation reaction. The addition time was controlled to 5 hours, and the mixture was incubated at -30°C for 4 hours. After incubation, 10% dilute sulfuric acid was added for neutralization, and the mixture was then heated to 35±5°C for hydrolysis and decarboxylation. After hydrolysis, 600mL of n-hexane was added for extraction, and the water layer was separated to obtain a n-hexane solution of 4-acetoxy-2-methylbutanal. The n-hexane was removed by vacuum distillation at 60±20°C, and the mixture was then decompressed to an absolute pressure of 1000 Pa. The product, 174.5g, of 4-acetoxy-2-methylbutanal was obtained. The GC content was 98.2%, and the yield was 77.8%.

[0098] The molar yield of 4-acetoxy-2-methylbutanal to 4-hydroxy-2-butanone was 77.2%.

[0099] Example 7

[0100] This example provides a method for synthesizing 4-acetoxy-2-methylbutanal, which comprises:

[0101] (1) Synthesis of 4-acetoxy-2-butanone

[0102] 275g of acetic anhydride was preheated to 50°C, followed by the dropwise addition of 176g of 4-hydroxy-2-butanone (2 mol). The addition was complete over 14 hours, and the reaction was continued at 50°C for 4 hours. After the reaction was completed, the absolute pressure was reduced to 40kPa, and the acetic acid and acetic anhydride were recovered by distillation at 80±10°C to obtain 259.7g of 4-acetoxy-2-butanone. The GC assay showed a content of 99.6%, and the yield was 99.5%.

[0103] (2) Synthesis of 4-acetoxy-2-methylbutyraldehyde

[0104] 235g of sodium tert-butoxide was dissolved in 500mL of methanol to obtain a sodium tert-butoxide solution, which was precooled to 10°C. 200g of 4-acetoxy-2-butanone (GC content 99.6%) was mixed with 220g of methyl chloroacetate and precooled to 10°C. The mixture was then added dropwise to the sodium tert-butoxide solution for a condensation reaction. The addition time was controlled to 6 hours, and the mixture was incubated at 10°C for 4 hours. After incubation, 15% dilute sulfuric acid was added for neutralization, and the mixture was then heated to 40±5°C for hydrolysis and decarboxylation. After hydrolysis, 500mL of petroleum ether was added for extraction, and the water layer was separated to obtain a petroleum ether solution of 4-acetoxy-2-methylbutanal. The petroleum ether was removed by vacuum distillation at 60±20°C, and then the mixture was decompressed to an absolute pressure of 1000 Pa and distilled at 100±10°C to obtain 192g of 4-acetoxy-2-methylbutanal product. The GC content was 99.2%, and the yield was 86.3%.

[0105] The molar yield of 4-acetoxy-2-methylbutanal to 4-hydroxy-2-butanone was 85.9%.

[0106] Example 8

[0107] This example provides a method for synthesizing 4-acetoxy-2-methylbutanal, which comprises:

[0108] (1) Synthesis of 4-acetoxy-2-butanone

[0109] 306g of acetic anhydride was preheated to 30°C, followed by the dropwise addition of 176g of 4-hydroxy-2-butanone (2 mol). The addition was complete over 15 hours, and the reaction was continued at 30°C for another 15 hours. After the reaction was completed, the pressure was reduced to 30kPa absolute, and the acetic acid and acetic anhydride were recovered by distillation at 70±10°C to obtain 259.7g of 4-acetoxy-2-butanone. The GC assay showed a content of 99.7%, for a yield of 99.6%.

[0110] (2) Synthesis of 4-acetoxy-2-methylbutyraldehyde

[0111] 200g of sodium methoxide was dissolved in 500mL of methanol to obtain a sodium methoxide solution, which was precooled to 20°C. 200g of 4-acetoxy-2-butanone (GC content 99.7%) was mixed with 250g of methyl chloroacetate and precooled to 20°C. The mixture was then added dropwise to the sodium methoxide solution for a condensation reaction. The addition time was controlled to 12 hours, and the mixture was incubated at 20°C for 3 hours. After incubation, 20% dilute sulfuric acid was added for neutralization, and the mixture was then heated to 55±5°C for hydrolysis and decarboxylation. After hydrolysis, 700mL of toluene was added for extraction, and the water layer was separated to obtain a toluene solution of 4-acetoxy-2-methylbutanal. Reduction by vacuum distillation at 70±20°C was performed to remove the toluene, and the mixture was then decompressed to an absolute pressure of 1000 Pa and distilled at 100±10°C to obtain 188.8g of the 4-acetoxy-2-methylbutanal product. The GC content was 98.5%, and the yield was 84.2%.

[0112] The molar yield of 4-acetoxy-2-methylbutanal to 4-hydroxy-2-butanone was 83.9%.

[0113] The above embodiments are intended only to illustrate the technical concepts and features of the present invention. Their purpose is to enable those skilled in the art to understand the contents of the present invention and implement them accordingly. They are not intended to limit the scope of protection of the present invention. Any equivalent changes or modifications made in accordance with the spirit of the present invention are intended to be covered by the scope of protection of the present invention.

[0114] The endpoints of the ranges and any values ​​disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoints of each range, the endpoints of each range and individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered to be specifically disclosed herein.

Claims

1. A method for synthesizing 4-acetoxy-2-methylbutanal, characterized in that: The synthesis method comprises: (1) Synthesis of 4-hydroxy-2-methylbutyraldehyde 129.6g of sodium methoxide was dissolved in 500mL of methanol to obtain a sodium methoxide solution, which was precooled to -10°C; 176g of 4-hydroxy-2-butanone was mixed with 238.7g of methyl chloroacetate and precooled to -10°C, and then added dropwise to the sodium methoxide solution for condensation reaction, the addition time was controlled to 5h, and the mixture was kept at -10°C for 2h after the addition was completed; 1000mL of water was added for hydrolysis at a hydrolysis temperature of 25±5°C; after the hydrolysis was completed, 500mL of n-hexane was added for extraction and the water layer was separated to obtain a n-hexane solution of 4-hydroxy-2-methylbutanal; the n-hexane was removed by vacuum distillation at 60±20°C, and then the pressure was reduced to an absolute pressure of 1000Pa, and the mixture was distilled at 100±10°C to obtain 175.5g of 4-hydroxy-2-methylbutanal product; (2) Synthesis of 4-acetoxy-2-methylbutyraldehyde 102.5 g of 4-hydroxy-2-methylbutanal with a GC content of 99.5% was preheated to 40°C; 122 g of acetic anhydride was then added dropwise over 4 hours, and the mixture was kept at 40°C for 20 hours. After the reaction was complete, the pressure was reduced to 50 kPa absolute, and acetic acid and acetic anhydride were recovered by distillation at 95±15°C to obtain 144.6 g of 4-acetoxy-2-methylbutanal product.

2. A method for synthesizing 4-acetoxy-2-methylbutanal, characterized in that: The synthesis method comprises: (1) Synthesis of 4-hydroxy-2-methylbutyraldehyde 307.2g of sodium tert-butoxide was dissolved in 500mL of methanol to obtain a sodium tert-butoxide solution, which was precooled to -30°C; 176g of 4-hydroxy-2-butanone was mixed with 282.1g of methyl chloroacetate and precooled to -30°C, and then added dropwise to the sodium tert-butoxide solution for condensation reaction, the addition time was controlled to 6h, and the mixture was kept at -30°C for 4h; after the incubation, 1000mL of water was added for hydrolysis at 55±5°C; after the hydrolysis, 500mL of petroleum ether was added for extraction and the water layer was separated to obtain a petroleum ether solution of 4-hydroxy-2-methylbutanal; the petroleum ether was removed by vacuum distillation at 60±20°C, and then the absolute pressure was reduced to 1000Pa, and the mixture was distilled at 100±10°C to obtain 177.9g of 4-hydroxy-2-methylbutanal product; (2) Synthesis of 4-acetoxy-2-methylbutyraldehyde 102.8 g of 4-hydroxy-2-methylbutanal with a GC content of 99.2% was preheated to 80°C; 132 g of acetic anhydride was then added dropwise over 8 hours, and the mixture was kept at 80°C for another 4 hours. After the reaction was complete, the pressure was reduced to an absolute pressure of 40 kPa, and acetic acid and acetic anhydride were recovered by distillation at 90±20°C to obtain 144.6 g of 4-acetoxy-2-methylbutanal product.

3. A method for synthesizing 4-acetoxy-2-methylbutanal, characterized in that: The synthesis method comprises: (1) Synthesis of 4-acetoxy-2-butanone 275 g of acetic anhydride was preheated to 50°C, and then 176 g of 4-hydroxy-2-butanone was added dropwise over 14 hours. The mixture was kept at 50°C for another 4 hours. After the reaction was complete, the pressure was reduced to 40 kPa absolute, and acetic acid and acetic anhydride were recovered by distillation at 80 ± 10°C to obtain 259.7 g of 4-acetoxy-2-butanone. (2) Synthesis of 4-acetoxy-2-methylbutyraldehyde 235 g of sodium tert-butoxide was dissolved in 500 mL of methanol to obtain a sodium tert-butoxide solution, which was precooled to 10° C. 200 g of 4-acetoxy-2-butanone with a GC content of 99.6% was mixed with 220 g of methyl chloroacetate and precooled to 10° C. The mixture was then added dropwise to the sodium tert-butoxide solution for a condensation reaction. The addition time was controlled to 6 h, and the mixture was kept at 10° C. for 4 h. After the addition was completed, 15% dilute sulfuric acid was added for neutralization, and the mixture was then heated to 40±5° C. for hydrolysis and decarboxylation. After the hydrolysis was completed, 500 mL of petroleum ether was added for extraction, and the water layer was separated to obtain a petroleum ether solution of 4-acetoxy-2-methylbutanal. The petroleum ether was removed by vacuum distillation at 60±20° C., and then the absolute pressure was reduced to 1000 Pa, and distillation was performed at 100±10° C. to obtain 192 g of 4-acetoxy-2-methylbutanal product.

4. A method for synthesizing 4-acetoxy-2-methylbutanal, characterized in that: The synthesis method comprises: (1) Synthesis of 4-acetoxy-2-butanone 306 g of acetic anhydride was preheated to 30°C, and then 176 g of 4-hydroxy-2-butanone was added dropwise over 15 h. The mixture was kept at 30°C for 15 h. After the reaction was completed, the pressure was reduced to 30 kPa absolute, and acetic acid and acetic anhydride were recovered by distillation at 70 ± 10°C to obtain 259.7 g of 4-acetoxy-2-butanone. (2) Synthesis of 4-acetoxy-2-methylbutyraldehyde 200 g of sodium methoxide was dissolved in 500 mL of methanol to obtain a sodium methoxide solution, which was precooled to 20° C. 200 g of 4-acetoxy-2-butanone with a GC content of 99.7% was mixed with 250 g of methyl chloroacetate and precooled to 20° C. The mixture was then added dropwise to the sodium methoxide solution for a condensation reaction. The addition time was controlled to 12 h, and the mixture was kept warm at 20° C. for 3 h. After the insulation, 20% dilute sulfuric acid was added for neutralization, and the temperature was raised to 55±5° C. for hydrolysis and decarboxylation. After the hydrolysis, 700 mL of toluene was added for extraction, and the water layer was separated to obtain a toluene solution of 4-acetoxy-2-methylbutanal. The toluene was removed by vacuum distillation at 70±20° C., and then the pressure was reduced to an absolute pressure of 1000 Pa and distilled at 100±10° C. to obtain 188.8 g of 4-acetoxy-2-methylbutanal product.

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