Beta-diketone compound and preparation method thereof

Abstract

The invention relates to the technical field of compound preparation, in particular to a beta-diketone compound and a preparation method thereof.The preparation method comprises the steps that 1, tetrahydrofuran and NaH are added into a reaction flask to be stirred, methyl caprate is added at the room temperature, and then the temperature is increased; 2, dropwise adding p-ethyl acetophenone, and keeping the temperature until the p-ethyl acetophenone disappears; 3, adding water into concentrated hydrochloric acid, cooling to 5-10 DEG C, dropwise adding the material liquid in the step 2 into a hydrochloric acid solution, and controlling the temperature to be 5-30 DEG C; 4, stirring for 30 minutes after quenching, standing for 20 minutes, separating an organic phase, extracting a water phase by using tetrahydrofuran, and combining the organic phases; 5, adding anhydrous sodium sulfate into an organic phase, drying for 1 hour, filtering, and washing a filter cake; step 6, concentrating the filtrate under reduced pressure until no liquid flows out; and 7, adding methanol and ethanol into the concentrate, cooling to 15 DEG C, adding a seed crystal, stirring until crystallization, cooling to-5 to-10 DEG C, growing the crystal, and filtering to obtain the beta-diketone compound. The method improves the atom utilization rate, is simple in process, reduces the emission of three wastes, and is environment-friendly.

Description

Technical Field

[0001] The present invention relates to the technical field of compound preparation, in particular to a beta-diketone compound and a preparation method thereof. Background Art

[0002] β-diketones are a class of compounds with widespread industrial applications, such as metal extraction and polymer stabilization. β-diketones are currently the best and most readily available organic stabilizers for halogenated polymers, such as PVC, and as such, these compounds have become increasingly important in industry. However, as technology advances, the requirements for environmental friendliness, product purity, and manufacturing costs in the development of β-diketones are increasing, making the use of expensive stabilizers and environmentally unfriendly reagents impractical in the polymer industry.

[0003] The most commonly used method for preparing β-diketones is the reaction of an ester with a carbonium ion of a ketone, as disclosed in European Patent EP 0 454 623 A1 (CIBA-GEIGY AG) and U.S. Patent No. 5 015 777 A (Witco). However, this method has the disadvantage of causing numerous side reactions, such as crotonylation and the formation of β-ketoesters.

[0004] For example, European Patent EP 0 454 623 A1 attempted to increase the yield of β-diketones by using dimethyl sulfoxide (DMSO, a relatively expensive solvent) with the addition of ethanol and conducting the reaction at low temperature in the presence of sodium hydroxide or an alcoholate. However, the yield of esters was only moderate.

[0005] Similarly, in U.S. Patent No. 5,015,777A, the solvent used is inexpensive and relatively easy to separate from the crude reaction mixture, but a large excess of ester is used. After removing the alkyl benzoate, the yield relative to the ester is only moderate to poor. Furthermore, the resulting reaction mixture with a low reaction yield cannot be used without efficient purification, and the large excess ester must be recycled, which is often expensive or undesirable. Summary of the Invention

[0006] The object of the present invention is to provide a β-diketone compound and a preparation method thereof, which can solve the above technical problems.

[0007] The present invention provides a method for preparing a β-diketone compound, comprising the following steps:

[0008] Step 1: Add tetrahydrofuran to a reaction flask, add NaH and stir, add methyl decanoate at room temperature, and then heat;

[0009] Step 2: Add p-ethylacetophenone dropwise to the reaction flask, keep warm after the addition is complete, and wait for the p-ethylacetophenone to disappear;

[0010] Step 3: Add concentrated hydrochloric acid to water, cool to 5-10°C for standby use, and dropwise add the reaction solution from step 2 to the hydrochloric acid solution, controlling the temperature at 5-30°C;

[0011] Step 4: After quenching, stir for 30 minutes, let stand for 20 minutes, separate the upper organic phase, extract the lower aqueous phase with tetrahydrofuran once again, stir again for 30 minutes, let stand for 20 minutes again, separate the upper organic phase, and combine the two organic phases;

[0012] Step 5: Add anhydrous sodium sulfate to the upper organic phase obtained in step 4, stir and dry at room temperature for 1 hour, then filter, and wash the filter cake with tetrahydrofuran;

[0013] Step 6: The filtrate is concentrated under reduced pressure until no liquid flows out, which is considered to be the completion of the concentration;

[0014] Step 7: Methanol and ethanol are added to the concentrate obtained in step 6, and seed crystals are added after cooling to 15°C. The mixture is stirred at this temperature until a large amount of solid precipitates. After precipitation, the liquid is cooled to -5 to -10°C, and the solid is grown at this temperature. The solid is then discharged and filtered to obtain a β-diketone compound.

[0015] Preferably, the temperature is raised to 60°C in step 1.

[0016] Preferably, the mass ratio of the methyl decanoate to p-ethylacetophenone is (1.28-1.38):1; the mass ratio of the NaH to p-ethylacetophenone is (0.29-0.40):1.

[0017] Preferably, the p-ethylacetophenone in step 2 is added dropwise for 1-1.5 hours and kept warm for 3-4 hours.

[0018] Preferably, in step 2, TLC (EA:PE=1:10) is used to monitor the disappearance of p-ethylacetophenone.

[0019] Preferably, the dropping time in step 3 is 1-1.5 h.

[0020] Preferably, in step 4, the combined organic phase is washed once more with a sodium chloride aqueous solution, stirred for 30 minutes, allowed to stand for 20 minutes for separation, and the upper organic phase is separated.

[0021] Preferably, the temperature during the reduced pressure concentration process in step 6 is 45-50°C.

[0022] Preferably, the mass ratio of methanol to ethanol in step 7 is 4:1.

[0023] The present invention also provides a β-diketone compound, which is prepared according to the above preparation method.

[0024] Beneficial effects:

[0025] The present method optimizes reaction conditions and the catalytic system to efficiently prepare a β-diketone compound using p-ethylacetophenone and methyl decanoate as raw materials. This method improves atom utilization, simplifies the process, reduces three waste emissions, and is environmentally friendly, all while operating within a safe range. Furthermore, by screening different solvents and combining the properties of the target compound, an innovative, inexpensive, and readily available mixed solvent is used for crystallization, yielding the target compound with a purity exceeding 99%. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] In order to more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the specific embodiments or the description of the prior art. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0027] Figure 1 HPLC spectrum of the product prepared in Example 1 of the present invention;

[0028] Figure 2 This is the HPLC spectrum of the product prepared in Example 2 of the present invention;

[0029] Figure 3 This is the H NMR spectrum of the product prepared in Example 2 of the present invention;

[0030] Figure 4 This is the NMR carbon spectrum of the product prepared in Example 2 of the present invention;

[0031] Figure 5 This is the HPLC spectrum of the product prepared in Example 3 of the present invention;

[0032] Figure 6 This is the HPLC spectrum of the product prepared in Example 4 of the present invention;

[0033] Figure 7 This is the HPLC spectrum of the product prepared in Example 5 of the present invention;

[0034] Figure 8 HPLC spectrum of the product prepared in Comparative Example 1 of the present invention;

[0035] Figure 9 This is the HPLC spectrum of the product prepared in Comparative Example 2 of the present invention;

[0036] Figure 10 This is the HPLC spectrum of the product prepared in Comparative Example 3 of the present invention;

[0037] Figure 11 This is the HPLC spectrum of the product prepared in Comparative Example 4 of the present invention;

[0038] Figure 12 This is the HPLC spectrum of the product prepared in Comparative Example 5 of the present invention; DETAILED DESCRIPTION

[0039] It should be noted that the following detailed descriptions are illustrative and intended to provide further explanation of the present application. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which the present application belongs.

[0040] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit the exemplary embodiments according to the present application. As used herein, unless the context clearly indicates otherwise, the singular also includes the plural. In addition, it should be understood that when the terms "comprise" and / or "include" are used in this specification, they indicate the presence of features, steps, operations, devices, components and / or combinations thereof.

[0041] The following will clearly and completely describe the technical solutions of the present invention in conjunction with the embodiments. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0042] The synthesis process of the β-diketone compound of the present invention is as follows:

[0043]

[0044] Example 1:

[0045] In a 250ml four-necked flask, add 60ml of THF (purchased from Sinopharm Chemical Reagent Co., Ltd., referred to as "Sinopharm Group", the same below) and 4.0g (0.17mol) of sodium hydride (purchased from Sinopharm Group) and adjust the material temperature to 25°C while stirring with a mechanical stirrer. Stir for 10 minutes to disperse evenly; then, add 13.2g (0.071mol) of methyl decanoate, stir and heat to 60°C, and add 10g (0.067mol) of p-ethylacetophenone at a constant speed through a constant pressure dropping funnel. The addition time is 1.5 hours, and then stir at 60°C for 4 hours. Monitor the reaction progress. After the reaction is completed, cool to 10°C and set aside.

[0046] In another reaction flask, add 20g of concentrated hydrochloric acid and 50g of water, cool to 10°C, and add the completed reaction solution dropwise to the hydrochloric acid solution. Adjust the pH of the solution to 2-3, maintain the temperature at 5-30°C, and continue the addition for 1.5 hours. After the addition is complete, stir at 25-30°C for 30 minutes, let stand for 20 minutes, separate the liquids, and take the upper organic phase. Extract the lower aqueous phase again with 20g of THF, stir for 30 minutes, let stand for 20 minutes, separate the liquids, and take the upper organic phase. Combine the two organic phases. Wash the organic phase again with sodium chloride aqueous solution, stir for 30 minutes, let stand for 20 minutes, separate the liquids, and take the upper organic phase. Add 5 g of anhydrous sodium sulfate to the upper organic phase, stir and dry at room temperature for 1 hour, then filter and wash the filter cake with 10 g of THF; concentrate the filtrate under reduced pressure at 50°C until no liquid flows out, and the concentration is considered complete; add 72 g of methanol and 18 g of ethanol to the concentrated oil, cool to 15°C, add seed crystals, and stir while keeping warm until a large amount of solid precipitates. After precipitation, cool the feed liquid to -10°C, keep warm and grow crystals for 1 hour, remove the material, filter or centrifuge to obtain a wet powder, and vacuum dry to obtain 17.3 g of a dry product with a yield of 85% and a purity of 98.3%.

[0047] Example 2

[0048] In a 250ml four-necked flask, add 60ml of THF (purchased from Sinopharm Chemical Reagent Co., Ltd., referred to as "Sinopharm Group", the same below) and 3.4g (0.14mol) of sodium hydride (purchased from Sinopharm Group) and adjust the material temperature to 25°C while stirring with a mechanical stirrer. Stir for 10 minutes to disperse evenly; then, add 13.2g (0.071mol) of methyl decanoate, stir and heat to 60°C, and add 10g (0.067mol) of p-ethylacetophenone at a constant speed through a constant pressure dropping funnel for 1.5 hours. Then, stir at 60°C for 4 hours and monitor the reaction progress. After the reaction is completed, cool to 10°C and set aside.

[0049] In another reaction flask, add 20g of concentrated hydrochloric acid and 50g of water, cool to 10°C, and add the completed reaction solution dropwise to the hydrochloric acid solution. Adjust the pH of the solution to 2-3, maintain the temperature at 5-30°C, and continue the addition for 1.5 hours. After the addition is complete, stir at 25-30°C for 30 minutes, let stand for 20 minutes, separate the liquids, and take the upper organic phase. Extract the lower aqueous phase again with 20g of THF, stir for 30 minutes, let stand for 20 minutes, separate the liquids, and take the upper organic phase. Combine the two organic phases. Wash the organic phase again with sodium chloride aqueous solution, stir for 30 minutes, let stand for 20 minutes, separate the liquids, and take the upper organic phase. Add 5 g of anhydrous sodium sulfate to the upper organic phase, stir and dry at room temperature for 1 hour, then filter and wash the filter cake with 10 g of THF; concentrate the filtrate under reduced pressure at 50°C until no liquid flows out, and the concentration is considered complete; add 72 g of methanol and 18 g of ethanol to the concentrated oil, cool to 15°C, add seed crystals, and stir while keeping warm until a large amount of solid precipitates. After precipitation, cool the feed liquid to -10°C, keep warm and grow crystals for 1 hour, remove the material, filter or centrifuge to obtain a wet powder, and vacuum dry to obtain 19.2 g of a dry product with a yield of 95% and a purity of 99.5%.

[0050] Example 3

[0051] In a 250ml four-necked flask, add 60ml of THF (purchased from Sinopharm Chemical Reagent Co., Ltd., referred to as "Sinopharm Group", the same below) and 2.9g (0.12mol) of sodium hydride (purchased from Sinopharm Group) and adjust the material temperature to 25°C while stirring with a mechanical stirrer. Stir for 10 minutes to disperse evenly; then, add 13.2g (0.071mol) of methyl decanoate, stir and heat to 60°C, and add 10g (0.067mol) of p-ethylacetophenone at a constant speed through a constant pressure dropping funnel for 1.5 hours. Then, stir at 60°C for 4 hours and monitor the reaction progress. After the reaction is completed, cool to 10°C and set aside.

[0052] In another reaction flask, add 20g of concentrated hydrochloric acid and 50g of water, cool to 10°C, and add the completed reaction solution dropwise to the hydrochloric acid solution. Adjust the pH of the solution to 2-3, maintain the temperature at 5-30°C, and continue the addition for 1.5 hours. After the addition is complete, stir at 25-30°C for 30 minutes, let stand for 20 minutes, separate the liquids, and take the upper organic phase. Extract the lower aqueous phase again with 20g of THF, stir for 30 minutes, let stand for 20 minutes, separate the liquids, and take the upper organic phase. Combine the two organic phases. Wash the organic phase again with sodium chloride aqueous solution, stir for 30 minutes, let stand for 20 minutes, separate the liquids, and take the upper organic phase. 5 g of anhydrous sodium sulfate was added to the upper organic phase, stirred and dried at room temperature for 1 h, and then filtered. The filter cake was washed with 10 g of THF; the filtrate was concentrated under reduced pressure at 50°C until no liquid flowed out, and the concentration was considered complete; 72 g of methanol and 18 g of ethanol were added to the concentrated oil, the temperature was lowered to 15°C, seed crystals were added, and the mixture was stirred at this temperature until a large amount of solid precipitated. After precipitation, the feed liquid was cooled to -10°C, kept warm and crystallized for 1 h, and the material was removed. The wet powder was filtered or centrifuged and dried in vacuo to obtain 18.0 g of a dry product with a yield of 89% and a purity of 99.1%.

[0053] Example 4

[0054] In a 250ml four-necked flask, add 60ml of THF (purchased from Sinopharm Chemical Reagent Co., Ltd., referred to as "Sinopharm Group", the same below) and 3.4g (0.14mol) of sodium hydride (purchased from Sinopharm Group) and adjust the material temperature to 25°C while stirring with a mechanical stirrer. Stir for 10 minutes to disperse evenly; then, add 12.8g (0.069mol) of methyl decanoate, stir and heat to 60°C, and add 10g (0.067mol) of p-ethylacetophenone at a constant speed through a constant pressure dropping funnel for 1.5 hours. Then, stir at 60°C for 4 hours and monitor the reaction progress. After the reaction is completed, cool to 10°C and set aside.

[0055] In another reaction flask, add 20g of concentrated hydrochloric acid and 50g of water, cool to 10°C, and add the completed reaction solution dropwise to the hydrochloric acid solution. Adjust the pH of the solution to 2-3, maintain the temperature at 5-30°C, and continue the addition for 1.5 hours. After the addition is complete, stir at 25-30°C for 30 minutes, let stand for 20 minutes, separate the liquids, and take the upper organic phase. Extract the lower aqueous phase again with 20g of THF, stir for 30 minutes, let stand for 20 minutes, separate the liquids, and take the upper organic phase. Combine the two organic phases. Wash the organic phase again with sodium chloride aqueous solution, stir for 30 minutes, let stand for 20 minutes, separate the liquids, and take the upper organic phase. Add 5 g of anhydrous sodium sulfate to the upper organic phase, stir and dry at room temperature for 1 h, then filter and wash the filter cake with 10 g of THF; concentrate the filtrate under reduced pressure at 50°C until no liquid flows out, and the concentration is considered complete; add 72 g of methanol and 18 g of ethanol to the concentrated oil, cool to 15°C, add seed crystals, and stir while keeping warm until a large amount of solid precipitates. After precipitation, cool the feed liquid to -10°C, keep warm and grow crystals for 1 h, remove the material, filter or centrifuge to obtain a wet powder, and vacuum dry to obtain 18.0 g of a dry product with a yield of 89% and a purity of 99.0%.

[0056] Example 5

[0057] In a 250ml four-necked flask, add 60ml of THF (purchased from Sinopharm Chemical Reagent Co., Ltd., referred to as "Sinopharm Group", the same below) and 3.4g (0.14mol) of sodium hydride (purchased from Sinopharm Group) and adjust the material temperature to 25°C while stirring with a mechanical stirrer. Stir for 10 minutes to disperse evenly; then, add 13.8g (0.074mol) of methyl decanoate, stir and heat to 60°C, and add 10g (0.067mol) of p-ethylacetophenone at a constant speed through a constant pressure dropping funnel. The addition time is 1.5 hours, and then stir at 60°C for 4 hours. Monitor the reaction progress. After the reaction is completed, cool to 10°C and set aside.

[0058] In another reaction flask, add 20g of concentrated hydrochloric acid and 50g of water, cool to 10°C, and add the completed reaction solution dropwise to the hydrochloric acid solution. Adjust the pH of the solution to 2-3, maintain the temperature at 5-30°C, and continue the addition for 1.5 hours. After the addition is complete, stir at 25-30°C for 30 minutes, let stand for 20 minutes, separate the liquids, and take the upper organic phase. Extract the lower aqueous phase again with 20g of THF, stir for 30 minutes, let stand for 20 minutes, separate the liquids, and take the upper organic phase. Combine the two organic phases. Wash the organic phase again with sodium chloride aqueous solution, stir for 30 minutes, let stand for 20 minutes, separate the liquids, and take the upper organic phase. Add 5 g of anhydrous sodium sulfate to the upper organic phase, stir and dry at room temperature for 1 hour, then filter and wash the filter cake with 10 g of THF; concentrate the filtrate under reduced pressure at 50°C until no liquid flows out, and the concentration is considered complete; add 72 g of methanol and 18 g of ethanol to the concentrated oil, cool to 15°C, add seed crystals, and stir while keeping warm until a large amount of solid precipitates. After precipitation, cool the feed liquid to -10°C, keep warm and grow crystals for 1 hour, remove the material, filter or centrifuge to obtain a wet powder, and vacuum dry to obtain 19.1 g of a dry product with a yield of 94% and a purity of 99.4%.

[0059] Comparative Example 1

[0060] The target compound was prepared according to the method of Example 2, except that an equal amount of DMF was added to the four-necked flask instead of tetrahydrofuran. The yield of the target compound was 93%.

[0061] Comparative Example 2

[0062] The target compound was prepared according to the method of Example 2, except that an equal amount of sodium methoxide was added to the four-necked flask instead of sodium hydride. Chromatographic analysis of the organic layer showed that the yield of the target compound was 55%.

[0063] Comparative Example 3

[0064] The target compound was prepared according to the method of Example 2, except that an equal amount of sodium tert-butoxide was added to the four-necked flask instead of sodium hydride. Chromatographic analysis of the organic layer showed that the yield of the target compound was 75%.

[0065] Comparative Example 4

[0066] The target compound was prepared according to the method of Example 2, except that the crystallization solvent was changed from a mixed solvent of methanol and ethanol to methanol. The yield of the target compound was 75% and the purity was 99.6%.

[0067] Comparative Example 5

[0068] The target compound was prepared according to the method of Example 2, except that the crystallization solvent was changed from a mixed solvent of methanol and ethanol to ethanol. The yield of the target compound was 96% and the purity was 97.5%.

[0069] From the comparison of Examples 1-3, it can be seen that the method for preparing the target compound of the present invention uses the sodium hydride feeding amount shown in Example 2, and the yield is the highest.

[0070] From the comparison of Examples 1-6, it can be seen that in the method for preparing the target compound of the present invention, the yield is the highest when the sodium hydride feeding amount and the methyl decanoate feeding amount shown in Example 2 are used.

[0071] From the comparison between Example 2 and Comparative Experiment 1, it can be seen that the yields of using DMF and THF as solvents in the method for preparing the target compound of the present invention are similar, but THF is preferred in consideration of recovery cost.

[0072] From the comparison of Example 2 and Comparative Experiments 2 and 3, it can be seen that the method for preparing the target compound of the present invention using sodium hydride shown in Formula Example 2 has the highest yield.

[0073] From the comparison between Example 2 and Comparative Experiments 4 and 5, it can be seen that the method for preparing the target compound of the present invention using the crystallization solvent shown in Example 2 has the highest yield.

[0074] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the above embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for preparing a β-diketone compound, characterized in that: The following steps are involved: Step 1: Add tetrahydrofuran to a reaction flask, add NaH and stir, add methyl decanoate at room temperature, and then heat; Step 2: Add p-ethylacetophenone dropwise to the reaction flask, keep warm after the addition is complete, and wait for the p-ethylacetophenone to disappear; Step 3: Add concentrated hydrochloric acid to water, cool to 5-10°C for standby use, and dropwise add the reaction solution from step 2 to the hydrochloric acid solution, controlling the temperature at 5-30°C; Step 4: After quenching, stir for 30 minutes, let stand for 20 minutes, separate the upper organic phase, extract the lower aqueous phase with tetrahydrofuran once again, stir again for 30 minutes, let stand for 20 minutes again, separate the upper organic phase, and combine the two organic phases; Step 5: Add anhydrous sodium sulfate to the upper organic phase obtained in step 4, stir and dry at room temperature for 1 hour, then filter, and wash the filter cake with tetrahydrofuran; Step 6: The filtrate is concentrated under reduced pressure until no liquid flows out, which is considered to be the completion of the concentration; Step 7: Methanol and ethanol are added to the concentrate obtained in step 6, and seed crystals are added after cooling to 15°C. The mixture is stirred at this temperature until a large amount of solid precipitates. After precipitation, the liquid is cooled to -5 to -10°C, and the solid is grown at this temperature. The solid is then discharged and filtered to obtain a β-diketone compound.

2. The method for preparing β-diketone compounds according to claim 1, wherein In the step 1, the temperature is raised to 60°C.

3. The method for preparing β-diketone compounds according to claim 1, wherein The mass ratio of the methyl decanoate to p-ethylacetophenone is (1.28-1.38):

1.

4. The method for preparing β-diketone compounds according to claim 1, wherein The p-ethylacetophenone in step 2 is added dropwise for 1-1.5 hours and kept warm for 3-4 hours.

5. The method for preparing β-diketone compounds according to claim 1, wherein In the step 2, TLC (EA:PE=1:10) was used to monitor the disappearance of p-ethylacetophenone.

6. The method for preparing β-diketone compounds according to claim 1, wherein The dropping time in step 3 is 1-1.5h.

7. The method for preparing β-diketone compounds according to claim 1, wherein In the step 4, the combined organic phases are washed once more with a sodium chloride aqueous solution, stirred for 30 minutes, allowed to stand for 20 minutes for separation, and the upper organic phase is separated.

8. The method for preparing β-diketone compounds according to claim 1, wherein The temperature during the reduced pressure concentration process in step 6 is 45-50°C.

9. The method for preparing β-diketone compounds according to claim 1, wherein The mass ratio of methanol to ethanol in step 7 is 4:

1.

10. A β-diketone compound, characterized in that Prepared according to any one of claims 1 to 9.

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