Preparation method of 2, 2, 4, 4-tetramethyl-1, 3-cyclobutanediol

Abstract

The invention discloses a preparation method of 2, 2, 4, 4-tetramethyl-1, 3-cyclobutanediol, and belongs to the technical field of organic synthesis. The method comprises the following steps: taking isobutyraldehyde as a raw material, and reacting with hydroxylamine hydrochloride in the presence of 1-butyl-3-methylimidazole chloride and a catalyst Bu4NPF6 to generate isobutyronitrile; reacting under the action of methyl trichlorosilane and methanol, and acidifying after alkaline hydrolysis to generate 2-methyl propionic acid; under the action of a dehydrating agent and triethylamine, 2, 2, 4, 4-tetramethyl-1, 3-cyclobutanedione is generated; finally, bis (2-methoxyethoxy) sodium aluminum hydride is adopted for reduction, and 2, 2, 4, 4-tetramethyl-1, 3-cyclobutanediol is obtained. The key point of the route is that 2, 2, 4, 4-tetramethyl-1, 3-cyclobutanedione is generated from 2-methylpropionic acid under the combined action of a dehydrating agent and triethylamine, and the method is simple and convenient to operate and suitable for industrial production.

Description

Technical Field

[0001] This invention relates to a method for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol, belonging to the field of organic synthesis technology. Background Technology

[0002] 2,2,4,4-Tetramethyl-1,3-cyclobutanediol (CBDO) is an important organic polymer raw material. It is mainly used in the synthesis of high-performance polyester materials, possessing high glass transition temperature, chemical resistance, and high transparency, and is widely used in home appliances, automobiles, and food packaging. Eastman Chemical Company in the United States monopolizes its production technology, while domestic companies such as Wanhua Chemical Group are also promoting pilot-scale and industrial-scale cooperation in related technologies. Regarding its safety, the median lethal dose (LD50) for acute oral toxicity in rats is 1500 mg / kg, classifying it as a low-toxicity substance and lacking genotoxicity. In food contact materials, both Chinese and EU regulations authorize its use as a monomer or starting material in the production of plastic food contact materials and products.

[0003] There are relatively few methods for synthesizing CBDO. Representative routes include those reported in patents [CN112457170A; CN105732329A; US2017 / 334815A1; KR2019 / 56665A], which use 2,2,4,4-tetramethyl-1,3-cyclobutanedione as a starting material and obtain the product CBDO through a reduction reaction. The chemical reaction equation is as follows:

[0004] There are two main routes for the synthesis of 2,2,4,4-tetramethyl-1,3-cyclobutanedione, as reported in patents and literature [CN112457170 A; Helvetica Chimica Acta, 1999, 82, 1302; KR2024 / 61949A; CN119661321A]. One route uses isobutyryl chloride as a raw material, which undergoes dehydrochlorination under the action of triethylamine to generate dimethyl ketene. This is followed by a dicondensation cyclization reaction to produce 2,2,4,4-tetramethyl-1,3-cyclobutanedione. The chemical reaction equation is as follows:

[0005] Patents [CN105732354A; KR2019 / 56665A; CN113443976A] report that 2-methylpropionic acid or 2-methylpropionic anhydride is used as raw material, and high-temperature catalytic cracking is carried out to generate dimethyl ketone, followed by a dicondensation cyclization reaction to generate 2,2,4,4-tetramethyl-1,3-cyclobutanedione.

[0006] In view of the shortcomings of the above-mentioned technical routes, it is necessary to conduct in-depth research on the synthesis route of CBDO and provide a newer process route to meet the growing market demand. Summary of the Invention

[0007] To overcome the aforementioned technical deficiencies, this invention provides a method for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol. The technical solution of this invention is as follows: isobutyraldehyde is used as a raw material and reacted with hydroxylamine hydrochloride in the presence of 1-butyl-3-methylimidazolium chloride and the catalyst Bu4NPF6 to generate isobutyronitrile; subsequently, it reacts with methyltrichlorosilane and methanol, followed by alkaline hydrolysis and acidification to generate 2-methylpropionic acid; then, in the presence of a dehydrating agent and triethylamine, 2,2,4,4-tetramethyl-1,3-cyclobutanedione is generated; finally, it is reduced with sodium bis(2-methoxyethoxy)aluminum hydride to obtain 2,2,4,4-tetramethyl-1,3-cyclobutanediol. This invention has a reasonable overall route, consisting of four steps, providing a simple and effective new route for the preparation of 2,2,4,4-tetramethyl-1,3-cyclobutanediol.

[0008] The method for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol according to the present invention is represented by the following reaction equation:

[0009] Includes the following steps: A. Isobutyraldehyde, hydroxylamine hydrochloride, [BMIm]Cl and Bu4NPF6 are mixed in an organic solvent and reacted under heating conditions to produce isobutyronitrile; B. Isobutyronitrile was mixed in methanol, and methyltrichlorosilane was added dropwise under low temperature conditions. After the reaction was completed, it was alkali-hydrolyzed and then acidified to obtain 2-methylpropionic acid. C. Mix the dehydrating agent and organic base in dichloromethane, add a dichloromethane solution of 2-methylpropionic acid at low temperature, and then heat the reaction to obtain 2,2,4,4-tetramethyl-1,3-cyclobutanedione. D. Mix 2,2,4,4-tetramethyl-1,3-cyclobutanedione in toluene, and add sodium bis(2-methoxyethoxy)aluminum hydride under low temperature conditions to generate 2,2,4,4-tetramethyl-1,3-cyclobutanediol.

[0010] Furthermore, in step A above, the organic solvent is selected from DMAc, DMF or DMSO; the heating conditions are 50℃~90℃.

[0011] Further, in step A above, the molar ratio of isobutyraldehyde, hydroxylamine hydrochloride, [BMIm]Cl to Bu4NPF6 is 1:1-1.2:1-1.2:0.02-0.06.

[0012] Furthermore, in step B above, the low temperature condition is -5℃ to 5℃.

[0013] Furthermore, in step B above, the molar ratio of isobutyronitrile to methyltrichlorosilane is 1:0.4-1.

[0014] Furthermore, in step B above, the alkali is selected from sodium hydroxide or potassium hydroxide solution; the acid is selected from hydrochloric acid or sulfuric acid.

[0015] Further, in step C above, the dehydrating agent is selected from 2-chloro-1,3-dimethylimidazoline chloromonium (DMC) or N,N'-dicyclohexylcarbodiimide (DCC); the organic base is selected from triethylamine or diisopropylethylamine; and the low temperature is -20℃ to 10℃.

[0016] Further, in step C above, the molar ratio of 2-methylpropionic acid, dehydrating agent and organic base is 1:1-1.2:0.005-0.015.

[0017] Furthermore, in step D above, the low temperature condition is -40℃ to 0℃.

[0018] Further, in step D above, the molar ratio of 2,2,4,4-tetramethyl-1,3-cyclobutanedione to sodium bis(2-methoxyethoxy)hydride is 1:1-3. Beneficial effects of the invention

[0019] 1. The raw materials, isobutyraldehyde and hydroxylamine hydrochloride, are inexpensive. Under the combined action of [BMIm]Cl and Bu4NPF6, isobutyronitrile is generated, resulting in a high reaction yield and simple operation.

[0020] 2. Hydrogen chloride is generated by reacting methyltrichlorosilane and alcohol, followed by reaction with nitrile Pinner to generate an imine ester hydrochloride intermediate. After alkaline hydrolysis and acidification, 2-methylpropionic acid is obtained. This method is convenient and avoids the use of hydrogen chloride gas.

[0021] 3. Using a dehydrating agent and triethylamine as catalysts, 2-methylpropionic acid is converted into a dimethyl ketene transition intermediate, which then undergoes a dimerization cyclization reaction to generate 2,2,4,4-tetramethyl-1,3-cyclobutanedione. This reduces the acyl chloride step, making the process simple, safe, and stable, and suitable for industrial-scale scaling. Detailed Implementation

[0022] The present invention will be further illustrated below with specific examples. These embodiments should be understood as illustrative only and not as limiting the scope of protection of the present invention. After reading the description of the present invention, those skilled in the art can make various alterations or modifications to the present invention, and these equivalent changes and modifications also fall within the scope defined by the claims of the present invention. Example 1

[0023]

[0024] Under nitrogen protection, isobutyraldehyde (7.2 g, 0.1 mol), hydroxylamine hydrochloride (7.3 g, 0.105 mol), [BMIm]Cl (17.5 g, 0.1 mol), and Bu4NPF6 (1.5 g, 4 mmol) were mixed in 100 mL of DMAc, heated to 60 °C, and reacted for 6 hours. The mixture was then cooled to room temperature and distilled under reduced pressure to obtain 6.77 g of isobutyronitrile, with a yield of 98% and a GC ≥ 99.5%. 1 HNMR(400MHz, CDCl3):2.71(t, 1H), 1.33(t, 6H) ppm. Example 2

[0025]

[0026] Under nitrogen protection, isobutyronitrile (6.9 g, 0.1 mol) was mixed in 50 mL of methanol and cooled to 0 °C. o Under C conditions, methyltrichlorosilane (9.0 g, 0.06 mol) was slowly added dropwise. After the addition was complete, the reaction continued for 6 hours. After the reaction was complete, the temperature was raised to room temperature, and excess methanol was concentrated under reduced pressure. The residue was added to 50 mL of NaOH (30%) aqueous solution, heated to 40 °C, stirred for 1 hour, cooled to room temperature, and the pH was adjusted to 4-5 by adding hydrochloric acid (2N). Sodium chloride solid was added to the reaction solution until saturation, and 50 mL of ethyl acetate was added for extraction twice. The organic layers were combined, concentrated, and distilled under reduced pressure to obtain 7.9 g of 2-methylpropionic acid, with a yield of 90% and a GC content of 99.3%. 1 HNMR (400 MHz, CDCl3): 11.66 (s, 1H), 2.55 (t, 1H), 1.18 (t, 6H) ppm. Example 3

[0027]

[0028] Under nitrogen protection, DMC (17.8 g, 0.105 mol) and triethylamine (0.1 g) were mixed in 150 mL of dichloromethane. The mixture was cooled to 0 °C, and a solution of 2-methylpropionic acid (8.8 g, 0.1 mol) in 100 mL of dichloromethane was slowly added dropwise. The mixture was then heated to room temperature and reacted for 2 hours, followed by reflux for 1 hour. The mixture was then cooled to room temperature, and 100 mL of water was added. The mixture was allowed to separate into two layers, and the organic layer was distilled under reduced pressure to obtain 4.8 g of 2,2,4,4-tetramethyl-1,3-cyclobutanedione, with a yield of 68% and a GC content of 98.9%. 1HNMR (400 MHz, CDCl3): 1.25 (s, 12H) ppm. Example 4

[0029]

[0030] Under nitrogen protection, DCC (21.7 g, 0.105 mol) and triethylamine (0.1 g) were mixed in 150 mL of dichloromethane and cooled to 0 °C. o At temperature C, a solution of 2-methylpropionic acid (8.8 g, 0.1 mol) in 100 mL of dichloromethane was slowly added dropwise. The mixture was then heated to room temperature and reacted for 2 hours, followed by reflux for 1 hour. The mixture was then cooled to room temperature, and 100 mL of water was added. The mixture was allowed to separate into two layers, and the organic layer was distilled under reduced pressure to obtain 4.3 g of 2,2,4,4-tetramethyl-1,3-cyclobutanedione, with a yield of 62% and a GC content of 98.7%. Example 5

[0031]

[0032] Under nitrogen protection, 14 g (0.1 mol) of 2,2,4,4-tetramethyl-1,3-cyclobutanedione was mixed in 50 mL of toluene. The mixture was cooled to -10 °C, and 57.8 g of a 70% sodium bis(2-methoxyethoxy)aluminum hydride solution in toluene was slowly added. After the addition was complete, the reaction was continued for 4 hours. The reaction mixture was then cooled to 0 °C. Extract twice with 100 mL of ethyl acetate to a 5% ammonium chloride (100 mL) aqueous solution at ℃. Combine the organic layers, concentrate, and distill under reduced pressure to obtain 11.2 g of 2,2,4,4-tetramethyl-1,3-cyclobutanediol, yield 78%, GC 99.6%. 1 HNMR (400 MHz, DMSO -d6): 4.51 (d, 2H), 3.15 (d,2H), 0.92 (s, 12H) ppm.

[0033] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A method for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol, characterized in that, Includes the following steps: ; A. Isobutyraldehyde, hydroxylamine hydrochloride, [BMIm]Cl and Bu4NPF6 are mixed in an organic solvent and reacted under heating conditions to produce isobutyronitrile; B. Isobutyronitrile was mixed in methanol, and methyltrichlorosilane was added dropwise under low temperature conditions. After the reaction was completed, it was alkali-hydrolyzed and then acidified to obtain 2-methylpropionic acid. C. Mix the dehydrating agent and organic base in dichloromethane, add a dichloromethane solution of 2-methylpropionic acid at low temperature, and then heat the reaction to obtain 2,2,4,4-tetramethyl-1,3-cyclobutanedione. D. Mix 2,2,4,4-tetramethyl-1,3-cyclobutanedione in toluene, and add sodium bis(2-methoxyethoxy)aluminum hydride under low temperature conditions to generate 2,2,4,4-tetramethyl-1,3-cyclobutanediol.

2. The method for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol according to claim 1, characterized in that: In step A, the organic solvent is selected from DMAc, DMF or DMSO; the heating conditions are 50℃~90℃.

3. The method for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol according to claim 1, characterized in that: In step A, the molar ratio of isobutyraldehyde, hydroxylamine hydrochloride, [BMIm]Cl and Bu4NPF6 is 1:1-1.2:1-1.2:0.02-0.

06.

4. The method for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol according to claim 1, characterized in that: In step B, the alkali is selected from sodium hydroxide or potassium hydroxide solution; the acid is selected from hydrochloric acid or sulfuric acid; and the low temperature condition is -5℃ to 5℃.

5. The method for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol according to claim 1, characterized in that: In step B, the molar ratio of isobutyronitrile to methyltrichlorosilane is 1:0.4-1.

6. The method for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol according to claim 1, characterized in that: In step C, the dehydrating agent is selected from 2-chloro-1,3-dimethylimidazoline chloronium or N,N'-dicyclohexylcarbodiimide; the organic base is selected from triethylamine or diisopropylethylamine; and the low temperature is -20℃ to 10℃.

7. The method for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol according to claim 1, characterized in that: In step C, the molar ratio of 2-methylpropionic acid, dehydrating agent and organic base is 1:1-1.2:0.005-0.

015.

8. The method for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol according to claim 1, characterized in that: In step D, the low temperature condition is -40℃ to 0℃.

9. The method for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol according to claim 1, characterized in that: In step D, the molar ratio of 2,2,4,4-tetramethyl-1,3-cyclobutanedione to sodium bis(2-methoxyethoxy)hydride is 1:1-3.

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