Recovery and Comprehensive Utilization of Monopropyl Malonate

Abstract

The present invention relates to a method for recovering monopropyl malonate of the chemical structural formula Ⅰ: Select 1-chloropropane and diethyl malonate in DMF, and under the action of potassium carbonate or sodium carbonate and quaternary ammonium salt, carry out dipropylation to obtain dipropyl malonate; in the process of preparing dipropyl malonate, add an alcohol solvent to the filter cake inorganic salt [residual dipropyl malonate monoester (Ⅲ)], and obtain the monopropyl malonate of the formula Ⅰ through pulping, acidification, crystallization, filtration and low-temperature vacuum drying: where M is selected from K or Na; R 1 is selected from: a C1-C5 straight-chain alkyl group or a C3-C5 branched-chain alkyl group; the alcohol solvent is selected from methanol, ethanol, a C3-C6 straight-chain or C3-C6 branched-chain monohydric alcohol, ethylene glycol, a C3-C5 straight-chain dihydric alcohol or a C4-C5 branched-chain dihydric alcohol; H + is selected from hydrochloric acid, phosphoric acid or sulfuric acid.

Description

Technical Field

[0001] The present invention relates to a method for recovering monopropyl malonate in the preparation process of dipropyl malonate and its application in the preparation of valproic acid by the malonic ester method. Background Art

[0002] Sichuan Core Pharmaceutical Co., Ltd. [A method for detecting dipropyl malonic acid related impurities, ZL201911229436.7, authorized on October 28, 2022] uses high performance liquid chromatography to detect the dipropyl malonic acid reaction solution. According to the elution order of HPLC and the peak area normalization method, its structural formula and content are listed in Table 1.

[0003] Table 1 HPLC detection results of dipropyl malonic acid reaction solution

[0004]

[0005] The HPLC detection results of the dipropyl malonic acid reaction solution show that it contains monomethyl dipropyl malonate (valproate sodium impurity 20) and monoethyl dipropyl malonate.

[0006] Peng Xiangyun and Xu Chengzhi [Study on solid-liquid phase alkylation reaction Ⅰ. Alkylation reaction of diethyl malonate and ethyl cyanoacetate with potassium carbonate as the base, Acta Chimica Sinica, 1983, 41(6):514-518] selected the reaction of diethyl malonate with 1-bromopropane for 12 h to prepare diethyl 2-propylmalonate with a yield of 66.8%, and the yield of diethyl dipropylmalonate (Ⅱ2) was 0.2%.

[0007]

[0008] Steffen et al. [Process for C-alkylation of unsubstituted and monosubstituted malonic acid esters. DE3737377, May 18, 1989] described that diethyl dipropylmalonate (Ⅱ2) was used as the solvent, sodium ethoxide was used as the base, and diethyl malonate and 1-chloropropane were reacted in a high-pressure reactor (3 bar to 4 bar) for 6 h to prepare diethyl dipropylmalonate Ⅱ2 with a yield of 81%.

[0009]

[0010] Beijing Yuekang Kechuang Pharmaceutical Technology Co., Ltd. [A method for preparing diethyl dipropylmalonate, CN115433081B, April 26, 2024] selects diethyl malonate and 1-bromopropane as starting materials, and reacts them in ethanol under the action of sodium ethoxide to produce diethyl dipropylmalonate. During the reaction, an additional operation is added to filter out sodium bromide in the reaction solution to make the reaction more complete.

[0011] Sichuan Core Pharmaceutical Co., Ltd. [A method for preparing diethyl dipropylmalonate, an intermediate of valproic acid, CN202111473302.7, June 6, 2023] discloses that diethyl malonate and 1-bromopropane react in an amide solvent under the action of a base and a phase transfer catalyst to obtain diethyl dipropylmalonate; controlling the impurity content of diethyl dipropylmalonate ≤ 0.17% (GC); the purity of diethyl dipropylmalonate ≥ 98.16% (GC), and the yield ≥ 85%:

[0012]

[0013] Peking University Founder Group Co., Ltd. et al. [Tao Jing, Lin Songwen, Zhong Xuechao, Deng Xiaobing. A crystallization method of 2,2-dipropylmalonic acid, ZL201110457073.X, August 12, 2015] describes a crystallization method of 2,2-dipropylmalonic acid: Crystallize the crude product of 2,2-dipropylmalonic acid in two mixed organic solvents (ethyl acetate, dichloromethane, tetrahydrofuran, acetonitrile, dioxane respectively with n-hexane, cyclohexane or petroleum ether) to obtain 2,2-dipropylmalonic acid, with a recovery rate of 65.0% - 74.5% and a purity of 99.50% - 99.78%.

[0014] Hunan University [A method for preparing dipropylmalonic acid using chloropropane as an alkylating agent and its application, CN116768697B, authorized on March 29, 2024; The preparation, hydrolysis and application of dimethyl dipropylmalonate, CN118373737A, July 23, 2024] discloses that diethyl malonate and 1-chloropropane react in an aprotic solvent such as DMF to prepare dimethyl dipropylmalonate (II), and II is hydrolyzed and decarboxylated to prepare valproic acid:

[0015]

[0016] II R = methyl or ethyl

[0017] When R is methyl, the reaction for preparing dimethyl dipropylmalonate (II1) is as follows:

[0018]

[0019] Hunan University [Preparation, hydrolysis and application of dimethyl dipropylmalonate, CN118373737A, July 23, 2024] In the process of preparing dimethyl dipropylmalonate Ⅱ1, the inorganic salt solid obtained by filtration may contain monomethyl dipropylmalonate potassium (Ⅲ1):

[0020]

[0021] When R is ethyl, the reaction for preparing diethyl dipropylmalonate (Ⅱ2) is as follows:

[0022]

[0023] Hunan University [Method and application for preparing dipropylmalonic acid using chloropropane as an alkylating agent, CN116768697B, authorized on March 29, 2024] In the process of preparing diethyl dipropylmalonate Ⅱ2, the inorganic salt solid obtained by filtration may contain monoethyl dipropylmalonate potassium (Ⅲ2):

[0024] Summary of the Invention

[0025] The purpose of the present invention is to provide a method for recovering the monoesters of dipropylmalonic acid shown in chemical structural formula Ⅰ:

[0026] 1-chloropropane and diethyl malonate react in DMF under the action of potassium carbonate or sodium carbonate and a quaternary ammonium salt to undergo dipropylation to obtain the dipropylmalonic acid diester shown in formula Ⅱ;

[0027]

[0028] M is selected from K or Na; R 1 is selected from: straight-chain alkyl groups with 1 to 5 carbon atoms or branched-chain alkyl groups with 3 to 5 carbon atoms; R 2 is selected from: straight-chain alkyl groups with 1 to 5 carbon atoms or branched-chain alkyl groups with 3 to 5 carbon atoms; R 1 is the same as or different from R 2 ; H + is selected from hydrochloric acid, phosphoric acid or sulfuric acid.

[0029] The dipropylmalonic acid diester is selected from dimethyl dipropylmalonate, diethyl dipropylmalonate, dipropyl dipropylmalonate, methyl ethyl dipropylmalonate, ethyl propyl dipropylmalonate, methyl propyl dipropylmalonate.

[0030] In the process of preparing dipropyl malonate (II), the inorganic salt solid obtained by filtration contains residual dipropyl malonate monoester (III); an alcohol solvent is added to the inorganic salt containing dipropyl malonate monoester III, and after pulping, acidification, crystallization, filtration and low-temperature vacuum drying, dipropyl malonic acid monoester shown in formula I is obtained; I is hydrolyzed to obtain dipropyl malonic acid, and the latter is decarboxylated to obtain valproic acid:

[0031]

[0032] M is selected from K or Na; H + is selected from hydrochloric acid, phosphoric acid or sulfuric acid; R 1 is selected from: C1-C5 straight-chain alkyl or C3-C5 branched-chain alkyl; the temperature of pulping is selected from 40°C to 90°C.

[0033] The alcohol solvent is selected from methanol, ethanol, C3-C6 straight-chain or C3-C6 branched-chain monohydric alcohols, ethylene glycol, C3-C5 straight-chain dihydric alcohols or C4-C5 branched-chain dihydric alcohols.

[0034] The C3-C6 straight-chain monohydric alcohol is selected from propanol, butanol, pentanol or hexanol;

[0035] The C3-C6 branched-chain monohydric alcohol is selected from isopropanol, tert-butanol, neopentyl alcohol or cyclohexanol;

[0036] The C3-C5 straight-chain dihydric alcohol is selected from 1,2-propanediol, 1,3-propanediol, 1,2-butanediol or 1,4-butanediol;

[0037] The C4-C5 branched-chain dihydric alcohol is selected from 2-methyl-1,3-propanediol or 2,2-dimethyl-1,3-propanediol.

[0038] The dipropyl malonic acid monoester is selected from dipropyl malonic acid monomethyl ester, dipropyl malonic acid monoethyl ester, dipropyl malonic acid monon-propyl ester, dipropyl malonic acid monoisopropyl ester, dipropyl malonic acid monon-butyl ester or dipropyl malonic acid monoter-butyl ester.

[0039] In the recovery of dipropyl malonic acid monoester, hydrochloric acid or sulfuric acid is used for acidification, and the acidification pH value is controlled at 1.0-3.5.

[0040] The present invention also provides a recovery method of dipropyl malonic acid monomethyl ester shown in chemical structural formula I1:

[0041] 1-chloropropane and dimethyl malonate in DMF, under the action of potassium carbonate and quaternary ammonium salt (PTC), undergo dipropylation to obtain dipropyl malonic acid dimethyl ester shown in formula II1; the preparation reaction is as follows:

[0042]

[0043] The dipropylated quaternary ammonium salt (PTC) is selected from: tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, tetrapropylammonium chloride, tetrapropylammonium bromide, tetrapropylammonium iodide, tetraethylammonium chloride, tetraethylammonium bromide, tetraethylammonium iodide, tetramethylammonium chloride, tetramethylammonium bromide, tetramethylammonium iodide, tetradecyltrimethylammonium chloride, tetradecyltrimethylammonium bromide, tetradecyltrimethylammonium iodide, cetyltrimethylammonium bromide, octadecyltrimethylammonium bromide, benzyltriethylammonium chloride, benzyltriethylammonium bromide, benzyltriethylammonium iodide, benzyltrimethylammonium chloride, benzyltrimethylammonium bromide or benzyltrimethylammonium iodide.

[0044] In the process of preparing dimethyl dipropylmalonate (Ⅱ1), the inorganic salt solid obtained by filtration contains residual monomethyl dipropylmalonate potassium (Ⅲ1); an alcohol solvent is added to the inorganic salt containing monomethyl dipropylmalonate potassium Ⅲ1, and after pulping, acidification, crystallization, filtration and low-temperature vacuum drying, monomethyl dipropylmalonate shown by formula Ⅰ1 is obtained; Ⅰ1 is hydrolyzed to obtain dipropylmalonic acid; dipropylmalonic acid is decarboxylated to obtain valproic acid.

[0045]

[0046] The alcohol solvent is selected from methanol, ethanol, C3-C6 straight-chain or C3-C6 branched-chain monohydric alcohols, ethylene glycol, C3-C5 straight-chain dihydric alcohols or C4-C5 branched-chain dihydric alcohols; H + is selected from hydrochloric acid, phosphoric acid or sulfuric acid. The temperature of pulping is selected from 40°C to 90°C.

[0047] In the recovery of monomethyl dipropylmalonate, hydrochloric acid or sulfuric acid is used for acidification, and the acidification pH value is controlled at 1.0-3.5.

[0048] The present invention also provides a method for recovering monoethyl dipropylmalonate shown by chemical structural formula Ⅰ2:

[0049] 1-chloropropane and diethyl malonate in DMF, under the action of potassium carbonate and quaternary ammonium salt, undergo dipropylation to obtain diethyl dipropylmalonate shown by formula Ⅱ2; the preparation reaction is as follows:

[0050]

[0051] The dipropylated quaternary ammonium salt (PTC) is selected from: tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, tetrapropylammonium chloride, tetrapropylammonium bromide, tetrapropylammonium iodide, tetraethylammonium chloride, tetraethylammonium bromide, tetraethylammonium iodide, tetramethylammonium chloride, tetramethylammonium bromide, tetramethylammonium iodide, tetradecyltrimethylammonium chloride, tetradecyltrimethylammonium bromide, tetradecyltrimethylammonium iodide, cetyltrimethylammonium bromide, octadecyltrimethylammonium bromide, benzyltriethylammonium chloride, benzyltriethylammonium bromide, benzyltriethylammonium iodide, benzyltrimethylammonium chloride, benzyltrimethylammonium bromide or benzyltrimethylammonium iodide.

[0052] In the process of preparing diethyl dipropylmalonate (Ⅱ2), the inorganic salt solid obtained by filtration contains residual monoethyl dipropylmalonate potassium (Ⅲ2); an alcohol solvent is added to the inorganic salt containing monoethyl dipropylmalonate potassium Ⅲ2, followed by pulping, acidification, crystallization, filtration and low-temperature vacuum drying to obtain monoethyl dipropylmalonate shown by formula Ⅰ2; the latter is hydrolyzed to obtain dipropylmalonic acid; dipropylmalonic acid is decarboxylated to obtain valproic acid.

[0053]

[0054] The alcohol solvent is selected from methanol, ethanol, C3-C6 straight-chain or C3-C6 branched-chain monohydric alcohols, ethylene glycol, C3-C5 straight-chain dihydric alcohols or C4-C5 branched-chain dihydric alcohols; H + is selected from hydrochloric acid, phosphoric acid or sulfuric acid.

[0055] The temperature of pulping is selected from 40°C to 90°C.

[0056] In the recovery of monoethyl dipropylmalonate, hydrochloric acid or sulfuric acid is used for acidification, and the acidification pH value is controlled at 1.0 to 3.5.

[0057] The present invention has the following advantages compared with the prior art:

[0058] (1) For the first time, the present invention recovers monoethyl dipropylmalonate shown by formula Ⅰ from the inorganic salt solid obtained in the post-treatment of the process for preparing diethyl dipropylmalonate by pulping in an alcohol solvent, and its structure is characterized and confirmed.

[0059]

[0060] (2) The recovered monoethyl dipropylmalonate is hydrolyzed and decarboxylated to obtain valproic acid.

[0061] (3) The recovery and utilization of monoethyl dipropylmalonate can improve the total yield of valproic acid; reduce the production cost of valproic acid; and also reduce the environmental protection pressure. Specific Embodiments

[0062] The present invention will be further described in detail below with reference to the embodiments.

[0063] Example 1

[0064] Preparation of dimethyl dipropylmalonate (Ⅱ1)

[0065]

[0066] 6.0 mmol of TBAB and 100 mL of DMF were stirred, and then 0.4 mol of potassium carbonate (200 mesh), 0.2 mol of dimethyl malonate and 0.6 mol of 1-chloropropane were added. The mixture was stirred and reacted at 75 °C to 130 °C for 12.0 h, and the excess 1-chloropropane was recovered; after the reaction was complete, the temperature was lowered to 40 °C, and the inorganic salts were filtered off (for the recovery of monomethyl dipropylmalonate); the filtrate was vacuum distilled at 80 - 90 °C to recover DMF, and a pale yellow liquid (dimethyl dipropylmalonate Ⅱ1) was obtained.

[0067] Example 2

[0068] Recovery of monomethyl dipropylmalonate (Ⅰ1)

[0069]

[0070] 60 mL of methanol was added to the inorganic salts obtained in Example 1, and the mixture was stirred and slurried at 50 °C. The inorganic salts were filtered off (the filter cake was dried to obtain potassium chloride). Concentrated hydrochloric acid was added to the combined filtrates to acidify to pH 1.5, methanol was distilled off, cooled, crystallized, filtered and dried under low temperature vacuum to obtain 1.5 g of monomethyl dipropylmalonate (Ⅰ1), with a melting point of 60 - 61 °C.

[0071] Monomethyl dipropylmalonate: 1 H NMR (400 MHz, DMSO-d6) δ: 0.86 (t, J = 7.2 Hz, 6H, CH3×2), 1.18–1.02 (m, 4H, CH2×2), 1.72 (t, J = 8.4 Hz, 4H, 2×CH2), 3.66 (s, 3H, OCH3); 13 C NMR (100 MHz, DMSO-d6) δ: 13.94, 16.65, 33.78, 51.68, 56.47, 171.81 and 172.26.

[0072] Example 3

[0073] Hydrolysis of monomethyl dipropylmalonate (Ⅰ1)

[0074]

[0075] In 6.0 g of monomethyl dipropylmalonate (Ⅰ1), an aqueous potassium hydroxide solution (3 g of KOH, 3 mL of H2O) and 2 mL of methanol were added. The mixture was heated to 95 °C for hydrolysis for 3 h, and then rotary evaporation was carried out to obtain a solid. The solid was dissolved in 10 mL of water, and the pH was adjusted to 1 with concentrated hydrochloric acid. A solid precipitated out, which was filtered by suction. The solid was recrystallized from an aqueous methanol solution to obtain 5.5 g of dipropylmalonic acid, with a melting point of 157 - 158 °C.

[0076] Alternatively, monomethyl dipropylmalonate and dimethyl dipropylmalonate Ⅱ1 obtained in Example 1 were combined for hydrolysis to prepare dipropylmalonic acid.

[0077] Dipropylmalonic acid: 1 H NMR (400 MHz, DMSO-d6) δ: 0.87 (t, J = 7.3 Hz, 6H, CH3×2), 1.07 - 1.19 (m, 4H, CH2×2), 1.65 - 1.74 (m, 4H, CH2×2), 12.56 (bs, 2H, COOH×2).

[0078] Example 4

[0079] Preparation of diethyl dipropylmalonate (Ⅱ2)

[0080]

[0081] 32.02 g (0.2 mol) of diethyl malonate, 6.0 mmol of tetrabutylammonium bromide, 55.2 g (0.4 mol) of anhydrous potassium carbonate, 100 mL of DMF, and 0.6 mol of 1-chloropropane were stirred and reacted at 70 - 130 °C for 12 h. The temperature was lowered to below 50 °C, and filtration by suction was carried out. The filter cake (inorganic salt) was used to recover monoethyl dipropylmalonate (Ⅰ2), and the filtrate was vacuum distilled to recover DMF to obtain a light yellow liquid (diethyl dipropylmalonate Ⅱ2).

[0082] Diethyl dipropylmalonate Ⅱ2: 1 H NMR (400 MHz, CDCl3) δ: 0.81 (t, J = 7.2 Hz, 6H, 2×CH3), 1.10–1.06 (m, 4H, 2×CH2), 1.40 (t, J = 7.2 Hz, 6H, 2×CH3), 1.79–1.68 (m, 4H, 2×CH2), 4.06 (q, J = 7.2 Hz, 4H, OCH2). 13 C NMR (101 MHz, CDCl3) δ: 13.7, 14.0, 17.0, 34.1, 57.2, 60.5 and 171.5.

[0083] Example 5

[0084] Recovery of monoethyl dipropylmalonate (Ⅰ2)

[0085]

[0086] 60 mL of ethanol was added to the inorganic salt obtained in Example 4, and the mixture was stirred and slurried at 60 °C. The inorganic salt was recovered by filtration (the filter cake was dried to obtain potassium chloride). Concentrated hydrochloric acid was added to the combined filtrate to acidify it to pH 1.5, and ethanol was recovered by distillation. After cooling, crystallization, filtration, and low-temperature vacuum drying, 1.0 g of ethyl dipropylmalonate (Ⅰ2) with a melting point of 59–60 °C was obtained.

[0087] Ethyl dipropylmalonate: 1 HNMR(400 MHz, DMSO-d6) δ: 0.86 (t, J = 7.2 Hz, 6H, CH3×2), 1.06–1.13 (m, 4H, CH2×2), 1.14 (t, J = 7.2 Hz, 3H, CH3), 1.69–1.74 (m, 4H, CH2×2), 4.06 (q, J = 7.2 Hz, 2H, OCH2); 13 C NMR(101 MHz, DMSO-d6) δ 13.8, 14.2, 16.9, 33.5, 56.7, 60.3, 171.4 and 172.6.

[0088] Example 6

[0089] Hydrolysis of ethyl dipropylmalonate (Ⅰ2)

[0090]

[0091] 13 g of ethyl dipropylmalonate (Ⅰ2), 10 g of 40% potassium hydroxide solution, and 3 mL of ethanol were refluxed for 3 h with stirring. Ethanol was recovered by distillation until dry, and a white solid was obtained. 15 mL of water was added to dissolve the solid, and the temperature was lowered to below 40 °C. Concentrated hydrochloric acid was added dropwise to adjust the pH of the solution to 1, and a solid was precipitated. The solid was filtered by suction, and the filter cake was washed with an appropriate amount of water to obtain 11 g of dipropylmalonic acid.

[0092] Alternatively, ethyl dipropylmalonate was hydrolyzed together with diethyl dipropylmalonate Ⅱ2 obtained in Example 4 to prepare dipropylmalonic acid.

[0093] Dipropylmalonic acid: 1 H NMR(400 MHz, DMSO-d6) δ: 0.87 (t, J = 7.2 Hz, 6H, CH3×2), 1.01–1.24 (m, 4H, CH2×2), 1.62–1.83 (m, 4H, CH2×2), 12.58 (bm, 2H, COOH).

[0094] Example 7

[0095] Preparation of dipropyl malonate (Ⅱ3)

[0096]

[0097] Select dipropyl malonate and prepare dipropyl malonate (Ⅱ3) according to the method of Example 1.

[0098] Example 8

[0099] Recovery of monopropyldipropylmalonate (Ⅰ3)

[0100]

[0101] Add 50 mL of propanol to the inorganic salts obtained in Example 7, stir and pulp at 70 °C, filter to recover the inorganic salts (the filter cake is dried to obtain potassium chloride), add concentrated hydrochloric acid to the combined filtrate to acidify to pH 1.5, distill to recover propanol, cool, crystallize, filter and dry under low-temperature vacuum to obtain monopropyldipropylmalonate (Ⅰ3).

[0102] Example 9

[0103] Hydrolysis of monopropyldipropylmalonate (Ⅰ3)

[0104]

[0105] Monopropyldipropylmalonate (Ⅰ3) is hydrolyzed according to the method of Example 3 to obtain dipropylmalonic acid.

[0106] Example 10

[0107] Preparation of valproic acid

[0108]

[0109] Prepared according to the methods of the invention patents [A method for preparing dipropylmalonic acid using chloropropane as an alkylating agent and its application, CN116768697B, authorized in Example 11 on March 29, 2024; A method for preparing dimethyldipropylmalonate and its hydrolysis and application, CN118373737A, Example 3 on July 23, 2024]: Add dipropylmalonic acid to the reaction flask, decarboxylate at 160 - 180 °C for 2 h to obtain a yellow liquid of valproic acid, and vacuum distill to obtain a colorless and transparent valproic acid.

[0110] Valproic acid: 11H NMR (400 MHz, DMSO-d6) δ: 0.86 (t, J = 7.2 Hz, 6H, CH3×2), 1.22~1.32 (m, 4H, CH2×2), 1.34~1.39 (m, 2H, CH2), 1.44~1.53 (m, 2H, CH2), 2.18~2.24 (m, 1H, CH), 11.99 (bs, 1H, COOH).

[0111] In this specification, the invention has been described with reference to specific embodiments thereof. However, it is obvious that various modifications and variations can be made without departing from the spirit and scope of the invention. Therefore, the specification should be regarded as illustrative rather than restrictive.

Claims

1. A method for recovering monopropyl malonate dibutyl ester shown in chemical structural formula Ⅰ: characterized in that 1-Chloropropane reacts with diethyl malonate in DMF under the action of potassium carbonate or sodium carbonate and a quaternary ammonium salt to undergo dipropylation to obtain dipropyl diethyl malonate; in the process of preparing dipropyl diethyl malonate, the inorganic salt solid obtained by filtration contains the monoester of dipropyl malonate shown in Formula III; an alcohol solvent is added to the inorganic salt containing the monoester of dipropyl malonate III, and after pulping, acidification, crystallization, filtration and low-temperature vacuum drying, the monoester of dipropyl malonate shown in Formula I is obtained; Among them, M is selected from K or Na; R 1 is selected from: C1-C5 linear alkyl or C3-C5 branched alkyl; the alcohol solvent is selected from methanol, ethanol, C3-C6 linear or C3-C6 branched monohydric alcohol, ethylene glycol, C3-C5 linear dihydric alcohol or C4-C5 branched dihydric alcohol; H + is selected from hydrochloric acid, phosphoric acid or sulfuric acid.

2. The method for recovering the monoester of dipropyl malonate according to claim 1, wherein the temperature of pulping is selected from 40°C to 90°C.

3. The method for recovering the monoester of dipropyl malonate according to claim 1, wherein the monoester of dipropyl malonate shown in Formula I is hydrolyzed to obtain dipropyl malonic acid, and the latter is decarboxylated to obtain valproic acid: Among them, M is selected from K or Na; R 1 is selected from: C1-C5 linear alkyl or C3-C5 branched alkyl; Or the monoester of dipropyl malonate and dipropyl diethyl malonate are combined and hydrolyzed to obtain dipropyl malonic acid, and then decarboxylated to obtain valproic acid.

4. The method for recovering the monoester of dipropyl malonate according to claim 1, wherein hydrochloric acid or sulfuric acid is used for acidification, and the pH value of acidification is controlled at 1.0 to 3.

5.

5. The method for recovering the monopropyl malonate as claimed in claim 1, characterized in that The alcohol solvent is selected from methanol, ethanol, C3-C6 straight-chain monohydric alcohols or C3-C6 branched-chain monohydric alcohols.

6. The recovery method of dipropyl malonic acid monoester according to claim 1, characterized in that The alcohol is selected from methanol, ethanol or C3-C6 straight-chain monohydric alcohols.

7. The method for recovering the monoester of dipropyl malonate according to claim 1: wherein the monoester of dipropyl malonate shown in Formula I is selected from monomethyl dipropyl malonate, monoethyl dipropyl malonate, monon-propyl dipropyl malonate, monoisopropyl dipropyl malonate, monon-butyl dipropyl malonate or monoter-butyl dipropyl malonate.

8. The method for recovering the monoester of dipropyl malonate according to claim 1: wherein the monoester of dipropyl malonate shown in Formula III is selected from monomethyl sodium dipropyl malonate, monoethyl sodium dipropyl malonate, monon-propyl sodium dipropyl malonate, monon-butyl sodium dipropyl malonate, monomethyl potassium dipropyl malonate, monoethyl potassium dipropyl malonate, monon-propyl potassium dipropyl malonate or monon-butyl potassium dipropyl malonate.

9. A method for recovering monomethyl dipropylmalonate shown in Chemical Structural Formula Ⅰ1, characterized in that 1-Chloropropane reacts with dimethyl malonate in DMF under the action of potassium carbonate and a quaternary ammonium salt to undergo dipropylation to obtain dimethyl dipropyl malonate; in the process of preparing dimethyl dipropyl malonate, the inorganic salt solid obtained by filtration contains monomethyl potassium dipropyl malonate shown in Formula III1; an alcohol solvent is added to the inorganic salt containing monomethyl potassium dipropyl malonate III1, and after pulping, acidification, crystallization, filtration and low-temperature vacuum drying, monomethyl dipropyl malonate shown in Formula I1 is obtained; Among them, H + and the definition of the alcohol solvent are as described in claim 1.

10. A method for recovering monoethyl dipropylmalonate shown in Chemical Structural Formula Ⅰ2, characterized in that 1-Chloropropane reacts with diethyl malonate in DMF under the action of potassium carbonate and a quaternary ammonium salt to undergo dipropylation to obtain diethyl dipropyl malonate; in the process of preparing diethyl dipropyl malonate, the inorganic salt solid obtained by filtration contains monoethyl potassium dipropyl malonate shown in Formula III2; an alcohol solvent is added to the inorganic salt containing monoethyl potassium dipropyl malonate III2, and after pulping, acidification, crystallization, filtration and low-temperature vacuum drying, monoethyl dipropyl malonate shown in Formula I2 is obtained: Among them, H + and the definition of the alcohol solvent is as described in claim 1.

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