Process for the preparation of stearoylbenzoyl methane derivatives

Abstract

The application discloses a preparation method of a stearylbenzoyl methane derivative, and the method steps are as follows: S1, adding a potassium tert-butoxide solution dissolved in an organic solvent to a phenylethanone derivative for activation under an inert atmosphere; S2, stirring the mixture after heating, and then adding methyl stearate dissolved in an organic solvent for reaction; S3, adding deionized water to quench the reaction after the reaction is completed, adjusting the pH to be acidic to precipitate solid materials, and obtaining the stearylbenzoyl methane derivative through vacuum filtration, washing and drying. The application uses phenylethanone derivatives and methyl stearate as raw materials, uses a solvent effect to enhance the activity of a catalyst, overcomes the problems of low yield and poor selectivity caused by para-substituted phenylethanone derivatives in a synthesis process, successfully synthesizes the stearylbenzoyl methane derivative with high yield and purity, and has the advantages of simple operation, good synthesis selectivity, mild reaction conditions and the like, and can improve the utilization rate of raw materials and reduce resource waste.

Description

TECHNICAL FIELD

[0001] The present application relates to the chemical technology field, and in particular to a preparation method of stearyl benzoyl methane derivative. BACKGROUND

[0002] Stearyl benzoyl methane derivative is a common β-diketone compound. Because of its keto and enol tautomerism, it can be used as an auxiliary heat stabilizer applied in the field of polyvinyl chloride (PVC) and as a good ultraviolet absorber applied in the field of cosmetics. It can be used in combination with calcium-zinc or rare earth heat stabilizers to improve the initial coloring of PVC products and effectively inhibit 'zinc burning'. The currently reported synthesis methods of stearyl benzoyl methane derivative include heating reflux method, soft enolization method, and alkyne ketone hydration method. The heating reflux method is generally used in industrial production, but this method has problems such as high energy consumption, long reaction time, and low yield.

[0003] A low-temperature synthesis route of stearyl benzoyl methane has been explored by the present research group, and stearyl benzoyl methane with high yield and purity has been obtained. However, when the reaction substrate is changed to a para-substituted acetophenone derivative, the electron cloud density on the benzene ring is increased due to the influence of the para-electron-donating group, which activates the benzene ring, resulting in a decrease in the activity of the substituted derivative during the nucleophilic substitution reaction. When this method is used for synthesis, the synthesis yield is greatly reduced, and many by-products are produced, and the selectivity is poor. Therefore, it is necessary to explore an environmentally friendly and simple synthesis route of β-diketone compounds, to improve the nucleophilic substitution activity of the reaction substrate and to improve the reaction selectivity. SUMMARY

[0004] Based on the technical problems existing in the background art, the present application provides a preparation method of stearyl benzoyl methane derivative, which uses acetophenone derivative and methyl stearate as raw materials and uses a method of enhancing the activity of the catalyst using solvent effect, overcomes the problems of low yield and poor selectivity caused by the para-substituted acetophenone derivative during the synthesis process, and successfully synthesizes stearyl benzoyl methane derivative with high yield and purity.

[0005] The preparation method of stearyl benzoyl methane derivative provided by the present application has the following steps:

[0006] S1: adding potassium tert-butoxide solution dissolved in an organic solvent to the acetophenone derivative under an inert atmosphere for activation;

[0007] S2: heating and stirring the mixture, and then adding methyl stearate dissolved in an organic solvent for reaction;

[0008] S3: After the reaction is completed, deionized water is added to quench the reaction, and the pH is adjusted to be acidic to precipitate solid materials. The hardening stearoyl benzoyl methane derivative is obtained by vacuum filtration, washing and drying.

[0009] Preferably, the acetophenone derivative is:

[0010]

[0011] wherein R = CH3O, CH3 or C(CH3)3.

[0012] Preferably, the organic solvent in S1 and S2 is one or more of dimethyl sulfoxide, N, N-dimethylformamide, hexamethylphosphoramide, toluene, tetrahydrofuran, 1, 3-dimethyl imidazolidinone, N-methyl pyrrolidone, acetonitrile.

[0013] Preferably, the molar ratio of the acetophenone derivative, the catalyst and the methyl stearate is 1:1.1-2:1.3-2.

[0014] Preferably, the temperature of the stirring in S2 is 45-50℃.

[0015] Preferably, the temperature of the reaction in S2 is 55-60℃, and the time is 3-4h.

[0016] Preferably, the pH adjustment in S3 is in the range of 6-6.8.

[0017] The beneficial technical effects of the present application are:

[0018] The present application increases the reactivity of the nucleophilic substitution of the para-substituted acetophenone derivative, improves the selectivity of the synthesis of the target product by the selection of the catalyst and the organic solvent. In addition, by changing the reaction conditions, the problems of low yield and poor selectivity of the para-substituted acetophenone derivative in the synthesis process are overcome, and the hardening stearoyl benzoyl methane derivative with high yield and purity is successfully synthesized. The preparation method has the advantages of simple operation, good synthesis selectivity, mild reaction conditions, etc., can improve the utilization rate of raw materials, and reduce resource waste. BRIEF DESCRIPTION OF DRAWINGS

[0019] Figure 1 The synthesis process flow chart of 1-(4-methoxyphenyl)-1, 3-eicosanedione prepared by example 1 proposed in the present application;

[0020] Figure 2 The nuclear magnetic resonance hydrogen spectrum of 1-(4-methoxyphenyl)-1, 3-eicosanedione prepared by example 1 proposed in the present application;

[0021] Figure 3NMR carbon spectrum of 1-(4-methoxyphenyl)-1,3-eicosanedione prepared in accordance with Example 1 of the present application;

[0022] Figure 4 Gas chromatography purity test chart of 1-(4-methoxyphenyl)-1,3-eicosanedione prepared in accordance with Example 1 of the present application;

[0023] Figure 5 NMR hydrogen spectrum of 1-(4-methylphenyl)-1,3-eicosanedione prepared in accordance with Example 2 of the present application;

[0024] Figure 6 NMR carbon spectrum of 1-(4-methylphenyl)-1,3-eicosanedione prepared in accordance with Example 2 of the present application;

[0025] Figure 7 Gas chromatography purity test chart of 1-(4-methylphenyl)-1,3-eicosanedione prepared in accordance with Example 2 of the present application;

[0026] Figure 8 NMR hydrogen spectrum of 1-(4-tert-butylphenyl)-1,3-eicosanedione prepared in accordance with Example 3 of the present application;

[0027] Figure 9 NMR carbon spectrum of 1-(4-tert-butylphenyl)-1,3-eicosanedione prepared in accordance with Example 3 of the present application;

[0028] Figure 10 Gas chromatography purity test chart of 1-(4-tert-butylphenyl)-1,3-eicosanedione prepared in accordance with Example 3 of the present application;

[0029] Figure 11 Gas chromatography purity test chart of 1-(4-methoxyphenyl)-1,3-eicosanedione prepared in accordance with the comparative example of the present application. DETAILED DESCRIPTION

[0030] The present application will be further explained in conjunction with specific examples.

[0031] Example 1

[0032] The present application proposes a synthesis method of 1-(4-methoxyphenyl)-1,3-eicosanedione, and the method steps are as follows:

[0033] Step one: according to the molar ratio of raw materials and catalyst 4-methoxyacetophenone: potassium tert-butoxide: methyl stearate = 1:1.25:1.3, accurately weigh the mass of the three substances, then add 3g of 4-methoxyacetophenone dissolved in 3mL of DMF into a 100mL dry three-necked round-bottom flask equipped with a stirrer, thermometer, then form a closed system and introduce N2, inject 2.805g of potassium tert-butoxide solution dissolved in 7mL of DMF to activate it within 30s, heat for about 15min to 50℃, at this time, add 7.454g of methyl stearate dissolved in 15mL of DMF, the temperature reaches 55℃, start the reaction and timing, stop heating and aeration after 3.5h of reaction;

[0034] Step two: after the system cools to room temperature, add hydrochloric acid to the reaction system to adjust the pH to about 6.5, then add 6 times the volume of deionized water (150mL) to precipitate the organic matter, and then filter the crude product under reduced pressure;

[0035] Step three: add methanol equivalent to three times the mass of the crude product, stir for two hours at room temperature, then filter to obtain the pure product, the mother liquor is recycled, and the pure product is placed in a vacuum drying oven for 12h to obtain 6.837g of light yellow solid, with a yield of 82.17%, and a purity of 97.12% determined by gas chromatography GC.

[0036] Figure 2 The H NMR spectrum of 1-(4-methoxyphenyl)-1,3-eicosanedione of the present application.

[0037] 1 H NMR (600 MHz, Chloroform-d) δ 7.87 (d, J = 8.6 Hz, 2H), 6.94 (d, J = 8.6 Hz, 2H), 6.11 (s, 1H), 3.87 (s, 3H), 2.39 (t, J = 7.5 Hz, 2H), 1.25 (s, 30H), 0.88 (t, J = 6.8 Hz, 3H).

[0038] Figure 3 The H NMR spectrum of 1-(4-methoxyphenyl)-1,3-eicosanedione of the present application.

[0039] 13 CNMR (101 MHz, Chloroform-d) δ 184.42, 163.10, 131.23, 129.18, 114.04, 113.97, 55.53, 38.88, 32.00, 29.77, 29.75, 29.73, 29.70, 29.67, 29.56, 29.47, 29.44, 29.38, 26.11, 22.77, 14.19.

[0040] Example 2

[0041] The present application provides a synthesis method of 1-(4-methylphenyl)-1,3-eicosanedione, which comprises the following steps:

[0042] Step one: according to the molar ratio of raw materials and catalyst, 4-methylacetophenone: potassium tert-butoxide: methyl stearate = 1:1.3:1.5, accurately weigh the mass of the three substances, then add 2.684 g of 4-methylacetophenone in a 100 mL dry three-necked round-bottom flask equipped with a stirrer and a thermometer, then form a closed system and introduce N2, drop 2.917 g of potassium tert-butoxide solution dissolved in 10 mL of DMF into the system within 30 s to activate it, heat for about 15 min to 48 ℃, at this time, add 8.955 g of methyl stearate dissolved in 15 mL of DMF, the temperature reaches 58 ℃, start the reaction and timing, stop heating and aeration after 4 h of reaction;

[0043] Step two: after the system cools to room temperature, add hydrochloric acid to the reaction system to adjust the pH to about 6.6, then add 6 times the volume of deionized water (150 mL) to precipitate the organic matter, and then obtain the crude product by vacuum filtration;

[0044] Step three: add methanol equivalent to three times the mass of the crude product, stir for two hours at room temperature, then filter to obtain the pure product, the mother liquor is recycled, and the pure product is placed in a vacuum drying oven for 12 h to obtain 6.736 g of yellow solid, with a yield of 84.2%, and a purity of 98.60% determined by gas chromatography (GC).

[0045] Figure 5 The present application provides a synthesis method of 1-(4-methylphenyl)-1,3-eicosanedione, which comprises the following steps:

[0046] 1 H NMR (600 MHz, Chloroform-d) δ 7.78 (d, J = 8.1 Hz, 1H), 7.26 (d, J = 8.6 Hz, 2H), 6.14 (s, 1H), 3.72 (s, 1H), 2.41 (s, 3H), 1.56 (s, 1H), 1.25 (s, 30H), 0.88 (t, J = 7.0 Hz, 3H).

[0047] Figure 6 The present application provides a synthesis method of 1-(4-methylphenyl)-1,3-eicosanedione, which comprises the following steps:

[0048] 13CNMR (101 MHz, Chloroform-d) δ 196.35, 184.01, 143.01, 132.52, 129.39, 127.14, 95.77, 59.12, 52.33, 39.20, 32.01, 29.78, 29.76, 29.74, 29.69, 29.56, 29.46, 29.44, 29.41, 29.38, 26.01, 22.77, 21.68, 14.20.

[0049] Example 3

[0050] The synthesis method of 1-(4-tert-butylphenyl)-1,3-eicosanedione provided by the present application comprises the following steps:

[0051] Step one: according to the molar ratio of raw materials and catalyst 4-tert-butylacetophenone: potassium tert-butoxide: methyl stearate = 1:1.5:1.2, accurately weigh the mass of the three substances, then add 3.525g of 4-tert-butylacetophenone in a 100mL dry three-necked round-bottom flask equipped with a stirrer and a thermometer, then form a closed system and introduce N2, drop 3.366g of potassium tert-butoxide solution dissolved in 10mL of DMF into the system within 30s to activate it, heat for about 15min to raise the temperature to 45℃, at this time, add 7.164g of methyl stearate dissolved in 15mL of DMF, the temperature reaches 60℃, start the reaction and timing, stop heating and aeration after 3.5h of reaction;

[0052] Step two: after the system cools to room temperature, add hydrochloric acid to the reaction system to adjust the pH to about 6.3, then add 6 times the volume of deionized water (150mL) to precipitate the organic matter, and then obtain the crude product by vacuum filtration;

[0053] Step three: add methanol equivalent to three times the mass of the crude product, stir for two hours at room temperature, then filter to obtain the pure product, the mother liquor is recycled, and the pure product is placed in a vacuum drying oven for 12h to obtain 7.302g of white solid powder, with a yield of 82.60%, and a purity of 97.69% determined by gas chromatography GC.

[0054] Figure 8 The nuclear magnetic resonance hydrogen spectrum of 1-(4-tert-butylphenyl)-1,3-eicosanedione provided by the present application.

[0055] 1H NMR (600 MHz, Chloroform-d) δ 7.82 (d, J = 8.2 Hz, 2H), 7.46 (d, J = 8.2 Hz, 2H), 6.15 (s, 1H), 2.41 (t, J = 7.6 Hz, 2H), 1.67 (p, J = 7.4 Hz, 2H), 1.34 (s, 9H), 1.25 (s, 28H), 0.89 (t, J = 7.0 Hz, 3H).

[0056] Figure 9 The carbon nuclear magnetic resonance spectrum of 1-(4-tert-butylphenyl)-1,3- eicosanedione of the present application.

[0057] 13 CNMR (101 MHz, Chloroform-d) δ 196.58, 183.80, 170.56, 156.04, 132.43, 128.80, 126.98, 125.84, 125.64, 95.88, 39.26, 35.12, 32.01, 31.20, 31.11, 29.73, 29.69, 29.67, 29.64, 29.60, 29.56, 29.54, 29.47, 25.99, 23.56, 14.10.

[0058] Comparative Example

[0059] Step one: accurately weigh the mass of the three substances according to the molar ratio of raw materials and catalyst 4-methoxyacetophenone: potassium tert-butoxide: methyl stearate = 1:1.25:1.3, then quickly add 7.454 g of methyl stearate and 2.805 g of potassium tert-butoxide into a 100 mL dry three-necked round-bottom flask equipped with a stirrer and a thermometer, then add 22 mL of DMF and replace the air in the system with nitrogen to form a closed environment, warm up to 55°C, start dropping 3 g of 4-methoxyacetophenone dissolved in 3 mL of DMF, stop heating and aeration after 3.5 h of reaction under the condition of keeping warm;

[0060] Step two: after the system cools to room temperature, add hydrochloric acid to the reaction system to adjust the pH to 6.5, then add 6 times the volume of deionized water (150 mL) to precipitate the organic matter, and then obtain the crude product by vacuum filtration;

[0061] Step three: add methanol equivalent to three times the mass of the crude product, stir for two hours at room temperature, then vacuum filter to obtain the pure product, the mother liquor is recycled, and the pure product is placed in a vacuum drying oven for 12 h to obtain 4.826 g of light yellow solid with a yield of 58.02%, and the purity determined by gas chromatography GC is 70.61%.

Claims

1. A process for the preparation of a stearylbenzoyl methane derivative, characterized in that, The method steps are as follows: S1: adding potassium tert-butoxide solution dissolved in an organic solvent to the acetophenone derivative for activation under an inert atmosphere; S2: heating and stirring the mixture, and then adding methyl stearate dissolved in an organic solvent for reaction; S3: after the reaction is completed, adding deionized water to quench the reaction, adjusting the pH to be acidic to precipitate solid materials, and then obtaining the stearoyl benzoyl methane derivative through vacuum filtration, washing and drying; The acetophenone derivative is: In the formula, R=CH3O, CH3 or -C(CH3)3.

2. The method for preparing a stearylbenzoylmethane derivative according to claim 1, characterized by, The organic solvent in S1 and S2 is one or several of dimethyl sulfoxide, N,N-dimethylformamide, hexamethylphosphoramide, toluene, tetrahydrofuran, 1,3-dimethyl imidazolidinone, N-methyl pyrrolidone and acetonitrile.

3. The method of producing a stearylbenzoylmethane derivative according to claim 1, characterized by, The molar ratio of the acetophenone derivative, potassium tert-butoxide and methyl stearate is 1:1.1-2:1.3-2.

4. The method of producing a stearylbenzoylmethane derivative according to claim 1, characterized by, The temperature for heating and stirring in S2 is 45-50°C.

5. The method of producing a stearylbenzoylmethane derivative according to claim 1, characterized by, The reaction temperature in S2 is 55-60°C, and the reaction time is 3-4h.

6. The method of producing a stearylbenzoylmethane derivative according to claim 1, characterized by, The pH range for adjustment in S3 is 6-6.8.

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