Preparation method of 5-oxohexanoate

Abstract

The invention discloses a preparation method of 5-oxohexanoate, and belongs to the field of organic synthesis. According to the invention, acetone, acrylate and an amino acid catalyst with a specific structure are reacted to obtain 5-oxohexanoate; wherein the structure of the catalyst is # imgabs0 #. The method is based on the specific amino acid catalyst and is matched with corresponding reaction environments (including media, auxiliaries and the like), so that side reactions can be effectively reduced, the reaction yield can be increased, and the reaction time can be greatly shortened; in addition, compared with a traditional mature process for preparing 5-oxohexanoate from acetylacetone and acrylate, the method disclosed by the invention also has the advantages of good molecular economy and no generation of redundant associated products.

Description

Technical Field

[0001] The invention relates to the field of organic synthesis, and in particular to a method for preparing 5-oxohexanoic acid ester. Background Art

[0002] 5-Oxohexanoic acid ester is an important chemical raw material that can be used to produce 1,3-cyclohexanedione, which is widely used in medicine, fragrances, new materials and other fields.

[0003] CN 112661639A discloses a method for obtaining methyl 5-oxohexanoate by using tetrahydropyrrole to catalyze the reaction of acetone and methyl acrylate. However, Chinese patent CN 114516796A clearly states that the method cannot be implemented.

[0004] CN 114516796A discloses a method for obtaining methyl 5-oxohexanoate by using dipotassium hydrogen phosphate, sodium bicarbonate or diethylamine to catalyze the reaction of acetone and methyl acrylate. Although the method can effectively obtain the target product methyl 5-oxohexanoate, the yield is low, and the maximum yield does not exceed 37%.

[0005] CN 116143622 A discloses a method for obtaining methyl 5-oxohexanoate by using amino alcohol compounds to catalyze the reaction of acetone and methyl acrylate. Although this method can achieve a relatively ideal reaction yield, the reaction time must be as long as 10-14 hours, and the production efficiency is relatively low.

[0006] In the article Michael addition of ethyl acrylate and acetone over solid bases (Catalysis Letters 59 (1999) 201–206), the following was reported:

[0007]

[0008] In the method for preparing 5-oxohexanoic acid ester by addition reaction of acetone and acrylic acid ester, dimethyl 5-oxoazelaate (BP1) is the main by-product. Further experiments by the applicant confirmed that dimethyl 5-oxoazelaate and 4-methyl-3-pentene-2-one (BP2) are also the main by-products of this type of reaction. In similar Michael addition reactions, the content of BP1 is generally as high as 25%-50%. This also leads to the generally low yield of the reaction. Summary of the invention

[0009] [Technical issues]

[0010] The present invention is conducted to solve the above-mentioned problems of low yield and low production efficiency of 5-oxohexanoic acid ester, and aims to provide a method for preparing 5-oxohexanoic acid ester with high yield which can reduce the occurrence of side reactions.

[0011] [Technical solution]

[0012] The present invention provides a method for preparing 5-oxohexanoic acid ester, and the reaction formula is as follows:

[0013]

[0014] In the above formula, R1 is a C1-C6 alkyl group,

[0015] The steps include:

[0016] In a sealed container, acetone, compound 2 and a catalyst react at a temperature of 130-200° C. to obtain compound 3, wherein the catalyst is

[0017] R2 and R3 are independently selected from H, C1-C6 alkyl, or R2, R3 and the atoms adjacent thereto together form a five-membered or six-membered heterocycloalkyl containing 1-2 heteroatoms, wherein the heteroatoms are selected from any one or two of N, O and S, and the multiple heteroatoms may be the same or different.

[0018] In one embodiment of the present invention, the catalyst is selected from any one or more of the following compounds:

[0019]

[0020] In one embodiment of the present invention, a polymerization inhibitor is also added during the reaction, and the amount of the polymerization inhibitor is 0.01%-0.2% by mass of compound 2, and specifically 0.1% can be selected.

[0021] In one embodiment of the present invention, the polymerization inhibitor is selected from any one or more of hydroquinone, p-benzoquinone, p-methylhydroquinone, p-tert-butylcatechol, 2-tert-butylhydroquinone, and 2,5-di-tert-butylhydroquinone.

[0022] In one embodiment of the present invention, the molar ratio of the catalyst to the compound 2 is (0.05-0.5):1, preferably (0.1-0.3):1.

[0023] In one embodiment of the present invention, the molar ratio of the acetone to the compound 2 is (3-15):1, preferably (5-10):1. Specifically, it can be 8:1.

[0024] In one embodiment of the present invention, compound 2 is specifically methyl acrylate.

[0025] In one embodiment of the present invention, the reaction temperature is 130-200°C, preferably 150-170°C, specifically 150°C, 160°C or 170°C.

[0026] In one embodiment of the present invention, the preparation method of 5-oxohexanoic acid ester comprises the following steps:

[0027] Acetone, compound 2, inhibitor and catalyst are added into a sealed container, and the temperature is raised to 130-200° C. for reaction. After the reaction is complete, compound 3 is obtained by distillation.

[0028] In one embodiment of the present invention, the reaction time is 2-24 hours. Further, 2-3 hours can obtain a high reaction yield.

[0029] In one embodiment of the present invention, the volume ratio of acetone to the volume of the sealed container is (2-3):5.

[0030] In one embodiment of the present invention, the conditions for distilling to obtain compound 3 are pressure 300-400 Pa and temperature 80-90°C.

[0031] Functions and Effects of the Invention

[0032] According to the method for preparing 5-oxohexanoic acid ester involved in the present invention, since an amino acid compound is used as a catalyst for the reaction, the method of the present invention can not only effectively reduce the occurrence of side reactions and improve the reaction yield, but also greatly shorten the reaction time. Furthermore, compared with the traditional mature process for preparing 5-oxohexanoic acid ester from acetylacetone and acrylate, the method has the advantages of good molecular economy and less generation of unnecessary by-products. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 is the hydrogen spectrum of 5-oxohexanoate prepared in Example 1 of the present invention;

[0034] Figure 2 It is the gas phase spectrum of 5-oxohexanoic acid ester prepared in Example 1 of the present invention. DETAILED DESCRIPTION

[0035] In order to make the technical means, creative features, objectives and effects achieved by the present invention easier to understand, the present invention is described in detail below in conjunction with embodiments and drawings.

[0036] In the following examples, unless otherwise specified, all raw materials are commercially available products.

[0037] <Example 1>

[0038]

[0039] Acetone (270mL, 3.72mol), methyl acrylate (40g, 0.46mol), p-tert-butylcatechol (40mg) and DL-proline (2.70g, 0.023mol) were added to a 500mL autoclave and heated to 150°C for 2 hours. After the reaction, the content of impurity BP1 in the reaction solution was 2.1%, and BP2 was not detected. The reaction solution was evaporated at 0.08-0.1MPa vacuum and 30-50°C to remove the remaining unreacted acetone and methyl acrylate, and then distilled under reduced pressure (300-400Pa, 80-90°C) to obtain methyl 5-oxohexanoate with a yield of 84.8% and a GC purity of 98.9% (the hydrogen spectrum of the product is shown in FIG. 2 ). Figure 1 As shown, the GC spectrum is Figure 2 As shown, the product is at a retention time of 9.261 min).

[0040] <Example 2>

[0041]

[0042] Acetone (270mL, 3.72mol), methyl acrylate (40g, 0.46mol), p-tert-butylcatechol (40mg) and sarcosine (4.10g, 0.046mol) were added to a 500mL autoclave and heated to 160°C for 2 hours. After the reaction, the impurity BP1 content in the reaction solution was 3.6%, and BP2 was not detected. The reaction solution was evaporated at 0.08-0.1MPa vacuum and 30-50°C to remove the remaining unreacted acetone and methyl acrylate, and then distilled under reduced pressure (300-400Pa, 80-90°C) to obtain methyl 5-oxohexanoate with a yield of 80.2% and a GC purity of 98.3%.

[0043] <Example 3>

[0044]

[0045] Acetone (270mL, 3.72mol), methyl acrylate (40g, 0.46mol), p-tert-butylcatechol (40mg) and DL-homoproline (5.94g, 0.046mol) were added to a 500mL autoclave and heated to 170°C for 2 hours. After the reaction, the impurity BP1 content in the reaction solution was 1.6%, and BP2 was not detected. The reaction solution was evaporated at 0.08-0.1MPa vacuum and 30-50°C to remove the remaining unreacted acetone and methyl acrylate, and then distilled under reduced pressure (300-400Pa, 80-90°C) to obtain methyl 5-oxohexanoate with a yield of 73.6% and a GC purity of 97.4%.

[0046] <Example 4>

[0047]

[0048] Acetone (270mL, 3.72mol), methyl acrylate (40g, 0.46mol) and DL-proline (2.70g, 0.023mol) were added to a 500mL autoclave and heated to 150°C for 2 hours. After the reaction, the impurity BP1 content in the reaction solution was 2.0%, and BP2 was not detected. The reaction solution was evaporated at 0.08-0.1MPa vacuum and 30-50°C to remove the remaining unreacted acetone and methyl acrylate, and then distilled under reduced pressure (300-400Pa, 80-90°C) to obtain methyl 5-oxohexanoate with a yield of 68.3%.

[0049] <Comparative Example 1>

[0050]

[0051] Acetone (270mL, 3.72mol), methyl acrylate (40g, 0.46mol), p-tert-butylcatechol (40mg) and ethanolamine (1.40g, 0.023mol) were added to a 500mL autoclave and heated to 150°C for 2 hours. After the reaction, the impurity BP1 content in the reaction solution was 0.8%, and the BP2 content was 13%. The reaction solution was evaporated at 0.08-0.1MPa vacuum and 30-50°C to remove the remaining unreacted acetone and methyl acrylate, and then distilled under reduced pressure (300-400Pa, 80-90°C) to obtain methyl 5-oxohexanoate with a yield of 37.7%.

[0052] <Comparative Example 2>

[0053] Acetone (106g, 1.84mol), DMSO (150mL), methyl acrylate (40g, 0.46mol), p-tert-butylcatechol (40mg) and DL-proline (2.70g, 0.023mol) were added to an autoclave and heated to 150°C for 2 hours. GC detected 3.9% BP1. After the reaction, the reaction solution was evaporated at 0.08-0.1MPa vacuum and 30-50°C to remove the solvent and methyl acrylate, and then distilled under reduced pressure (300-400Pa, 80-90°C) to obtain methyl 5-oxohexanoate with a yield of 51.2% and a purity of 97.3%.

[0054] <Comparative Example 3>

[0055] Acetone (106g, 1.84mol), tetrahydrofuran (150mL), methyl acrylate (40g, 0.46mol), p-tert-butylcatechol (40mg) and DL-proline (2.70g, 0.023mol) were added to an autoclave and heated to 150°C for 2 hours. GC detected 3.9% BP1. After the reaction, the reaction solution was evaporated at 0.08-0.1MPa vacuum and 30-50°C to remove the solvent and methyl acrylate, and then distilled under reduced pressure (300-400Pa, 80-90°C) to obtain methyl 5-oxohexanoate with a yield of 53.7% and a purity of 98.1%.

[0056] Functions and Effects of the Embodiments

[0057] According to the preparation method of 5-oxohexanoic acid ester involved in the above embodiment, since an amino acid compound is used as a catalyst for the reaction, the preparation method of the present invention can not only effectively reduce the occurrence of side reactions and improve the reaction yield, but also greatly shorten the reaction time. Compared with the traditional mature process for preparing 5-oxohexanoic acid ester from acetylacetone and acrylate, the advantage is that the molecular economy is good, no unnecessary by-products are generated, and it is conducive to product purification.

[0058] According to the method for preparing 5-oxohexanoic acid ester involved in the above embodiment, since a polymerization inhibitor is added to the reaction system, the reaction yield can be improved by reducing the generation of polymers.

[0059] According to the method for preparing 5-oxohexanoic acid ester involved in the above embodiment, since acetone is used as the reaction medium environment, a better reaction yield can be obtained; while when other medium environments such as DMSO are selected, the yield of 5-oxohexanoic acid ester is lower.

[0060] According to the method for preparing 5-oxohexanoic acid ester involved in the above embodiment, since no additional reaction solvent is required and the amount of catalyst used is a catalytic amount, not only the reaction cost is greatly reduced, but also the catalyst can be recovered after the product is distilled out of the reaction system.

[0061] The above-mentioned embodiments are preferred examples of the present invention and are not intended to limit the protection scope of the present invention.

Claims

1. A method for preparing 5-oxohexanoic acid ester, characterized in that: The reaction formula is as follows: In the above formula, R1 is a C1-C6 alkyl group, The steps include: Acetone and compound 2 react under the action of a catalyst to obtain compound 3. Wherein, the catalyst is R2 and R3 are independently selected from H, C1-C6 alkyl, or R2, R3 and the atoms adjacent thereto together form a five-membered or six-membered heterocycloalkyl containing 1-2 heteroatoms, wherein the heteroatoms are selected from any one or two of N, O and S, and the multiple heteroatoms may be the same or different.

2. The method for preparing 5-oxohexanoic acid ester according to claim 1, characterized in that: in, The catalyst is selected from any one or more of the following compounds:

3. The method for preparing 5-oxohexanoic acid ester according to claim 1, characterized in that: in, A polymerization inhibitor is also added during the reaction, and the amount of the polymerization inhibitor is 0.01%-0.2% of the mass of compound 2.

4. The method for preparing 5-oxohexanoic acid ester according to claim 3, characterized in that: in, The polymerization inhibitor is selected from any one or more of hydroquinone, p-benzoquinone, p-methylhydroquinone, p-tert-butylcatechol, 2-tert-butylhydroquinone, and 2,5-di-tert-butylhydroquinone.

5. The method for preparing 5-oxohexanoic acid ester according to claim 1, characterized in that: in, The molar ratio of the catalyst to the compound 2 is (0.05-0.5):

1.

6. The method for preparing 5-oxohexanoic acid ester according to claim 1, characterized in that: in, The molar ratio of the acetone to the compound 2 is (3-15):

1.

7. The method for preparing 5-oxohexanoic acid ester according to claim 1, characterized in that: in, Compound 2 is methyl acrylate.

8. The method for preparing 5-oxohexanoic acid ester according to claim 1, characterized in that: The steps include: Acetone, compound 2, inhibitor and catalyst are added into a sealed container, and the temperature is raised to 130-200° C. for reaction. After the reaction is complete, compound 3 is obtained by distillation.

9. The method for preparing 5-oxohexanoic acid ester according to claim 8, characterized in that: in, The volume ratio of acetone to the volume of the closed container is (2-3):

5.

10. The method for preparing 5-oxohexanoic acid ester according to claim 8, characterized in that: in, The conditions for distilling to obtain compound 3 are pressure 300-400 Pa and temperature 80-90°C.

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