Recovery and application of 2-cyano-2-methylvaleric acid

Abstract

The invention belongs to the field of pharmaceutical chemical engineering and fine chemical engineering, and relates to a method for recovering 2-cyano-2-methylvaleric acid as shown in a chemical structural formula I. The method comprises the following steps: selecting methyl 2-cyanoacetate and 1-chloropropane, and carrying out catalytic dipropylation under the action of potassium carbonate to prepare methyl 2-cyano-2-valproate; hydrolyzing the latter to obtain 2-cyano-2-valproic acid (crude product) as shown in a formula III; adding water, alcohol and other polar solvents into the 2-cyano-2-valproic acid crude product, pulping, carrying out gradient crystallization, filtering, and carrying out low-temperature vacuum drying to obtain 2-cyano-2-valproic acid monohydrate and 2-cyano-2-methylvalproic acid monohydrate; the 2-cyano-2-valproic acid monohydrate is subjected to high-temperature decarboxylation hydrolysis through sulfuric acid, and valproic acid is prepared; and carrying out high-temperature decarboxylation hydrolysis on the 2-cyano-2-methylpentanoic acid monohydrate by using sulfuric acid to obtain the essence 2-methylpentanoic acid.

Description

Technical Field

[0001] This invention relates to the fields of pharmaceutical chemicals and fine chemicals. Specifically, it concerns the recovery of 2-cyano-2-methylvaleric acid in the preparation of 2-cyano-2-propvaleric acid via the methyl 2-cyanoacetate method and its application in the preparation of dihydrostachial acid. Background Technology

[0002] 2-Methylvalerate (L), also known as dihydrostrawberry acid, is a colorless or pale yellow liquid, soluble in water and organic solvents such as ethanol; bp. 195–196℃; it has a strong, pungent, and unpleasant acid odor, and when highly diluted, it has an oily acid odor and a grassy aroma. It is used to formulate flavorings for dairy products, tomatoes, strawberries, grapes, cocoa, chocolate, coffee, and other food products.

[0003] The main process impurities in the preparation of valproic acid using the methyl 2-cyanoacetate method [A composite catalytic preparation method of methyl 2-cyano-2-propanolate, ZL2022101320660, authorized on 2023.3.31] are 2-methylpentanoic acid (L). The main process impurities in the preparation of valproic acid using the ethyl 2-cyanoacetate method [A preparation method and application of 2-cyano-2-propanolic acid, ZL2022101320389, authorized on 2023.03.17] are 2-ethylpentanoic acid (B). Hunan Xiangzhong Pharmaceutical Co., Ltd. and Hunan University [A detection method for impurities in the preparation of valproic acid using the methyl cyanoacetate method, CN202311045924.9, 2023.11.17] have disclosed their detection methods.

[0004]

[0005] Hunan Xiangzhong Pharmaceutical Co., Ltd. [A method for preparing 2-cyano-2-propylvalerate and valproic acid, CN119930467A, 2025.5.6] describes the main impurities in the methyl 2-cyanoacetate method and the ethyl 2-cyanoacetate method for preparing valproic acid as 2-methylvaleric acid (L) and 2-ethylvaleric acid (B), respectively.

[0006] Shanghai Qingping Pharmaceutical Co., Ltd. [A 2-R] 1 The preparation method of valerate, CN 202110336630.6, 2021.7.23] describes the reaction of methyl 2-cyanoacetate, methanol and 1-bromopropane at 45-60 °C with the dropwise addition of 30-40% sodium methoxide methanol solution. After the reaction is completed, the methanol is rotary evaporated to obtain crude product, which is then purified to obtain methyl 2-cyanopentate. Methyl 2-cyanopentate is then methylated, hydrolyzed and decarboxylated to obtain 2-methylvalerate (L).

[0007]

[0008] Currently, the residual amount of 2-methylvaleric acid L in sodium valproate raw materials is relatively high. Pharmacological tests have shown that 2-methylvaleric acid L has vascular irritant properties, which can cause vascular irritation in sodium valproate injections [A highly safe pharmaceutical composition and its preparation method, ZL201911306074.7, authorized on 2023.3.21]. Therefore, it is necessary to control the generation of 2-methylvaleric acid L during the synthesis of sodium valproate raw materials to reduce vascular irritation. Sichuan Keruide Pharmaceutical Co., Ltd. provides a highly safe pharmaceutical composition that can reduce the vascular irritation of injectable sodium valproate [A highly safe pharmaceutical composition and its preparation method, ZL201911306074.7, authorized on 2023.3.21], wherein the pharmaceutical composition contains not less than 90% sodium valproate and not more than 0.014% 2-methylvaleric acid L.

[0009] 2-Methylvalerate is an impurity that is easily generated during the preparation of sodium valproate raw material, and it plays a crucial role in the detection and control of related substances in the production of sodium valproate raw material. The European Pharmacopoeia and the British Pharmacopoeia have reported on the research and control applications of 2-methylvalerate (L) impurity in sodium valproate.

[0010] 2-Methylvalerate, 2-ethylvalerate, and valproic acid (2-propylvalerate) are homologues of monocarboxylic acids with similar physical properties. 2-Methylvalerate, 2-ethylvalerate, and valproic acid are all liquids with similar boiling points. Although the content of 2-methylvalerate and 2-ethylvalerate is low, they are easier to distill off due to their lower boiling points. Therefore, it is difficult to completely separate and remove 2-methylvalerate and 2-ethylvalerate from the active pharmaceutical ingredient valproic acid by distillation. Summary of the Invention

[0011] The purpose of this invention is to find the precursor compound of 2-methylvaleric acid, 2-cyano-2-methylvaleric acid, by using reverse functional group exchange (FGI) and reverse functional group addition (FGA) in the retrosynthetic analysis method.

[0012]

[0013] The purpose of this invention is to find the precursor compound of 2-ethylpentanoic acid, namely 2-cyano-2-ethylpentanoic acid, by using reverse functional group exchange (FGI) and reverse functional group addition (FGA) in the retrosynthetic analysis method.

[0014]

[0015] The purpose of this invention is to find the valproic acid precursor compound, 2-cyano-2-valproic acid, using reverse functional group exchange (FGI) and reverse functional group addition (FGA) in the retrosynthetic analysis method.

[0016]

[0017] The precursor compounds of 2-methylvaleric acid and 2-ethylvaleric acid and valproic acid are 2-cyano-2-methylvaleric acid, 2-cyano-2-ethylvaleric acid, and 2-cyano-2-valproic acid (III). 2-cyano-2-methylvaleric acid and 2-cyano-2-ethylvaleric acid are chiral liquid compounds; 2-cyano-2-valproic acid is an achiral compound with a melting point of 33°C.

[0018]

[0019] The structural formulas of the monohydrates formed by 2-cyano-2-methylpentanoic acid (I), 2-cyano-2-ethylpentanoic acid (II), and 2-cyano-2-propanolanoic acid (III) with water are as follows:

[0020]

[0021] The monohydrates of 2-cyano-2-methylvaleric acid (I), 2-cyano-2-ethylvaleric acid (II), and 2-cyano-2-propvaleric acid (III) are solids at low temperatures. Their solid melting points and solubilities in polar solvents differ. The crude 2-cyano-2-methylvaleric acid (I) and 2-cyanovaleric acid, or 2-cyano-2-ethylvaleric acid (II) and 2-cyanovaleric acid, can be effectively separated by slurrying and gradient crystallization.

[0022] The purpose of this invention is to prepare 2-cyano-2-propvaleric acid by the methyl 2-cyanoacetate method; to separate 2-cyano-2-methylvaleric acid and 2-cyanovaleric acid from the crude 2-cyano-2-propvaleric acid by a pulping method, and to purify and obtain 2-cyano-2-propvaleric acid monohydrate.

[0023] The purpose of this invention is to prepare 2-cyano-2-propvaleric acid by selecting the ethyl 2-cyanoacetate method; to separate 2-cyano-2-ethylpentanoic acid and 2-cyanopentanoic acid from the crude 2-cyano-2-propvaleric acid by a pulping method, and to purify and obtain 2-cyano-2-propvaleric acid monohydrate.

[0024] The objective of this invention is to select a method for preparing 2-cyano-2-propvaleric acid via the methyl 2-cyanoacetate process, and to recover 2-cyano-2-methylvaleric acid from the crude product by pulping and gradient crystallization.

[0025] The purpose of this invention is to prepare 2-methylvaleric acid, a food flavoring, by decarboxylating 2-cyano-2-methylvaleric acid or its monohydrate at high temperature; turning waste into treasure; 2-methylvaleric acid (L) is obtained by decarboxylating and hydrolyzing 2-cyano-2-methylvaleric acid or its monohydrate; L, also known as dihydrostrawberry acid, is used to prepare flavorings.

[0026]

[0027] Compared with the prior art, the present invention has the following advantages:

[0028] (1) 2-Cyano-2-propvaleric acid was prepared by the methyl 2-cyanoacetate method; 2-cyano-2-methylvaleric acid and 2-cyanovaleric acid were separated from the crude 2-cyano-2-propvaleric acid by pulping, and 2-cyano-2-propvaleric acid monohydrate was obtained by purification; the content of 2-cyano-2-methylvaleric acid impurities decreased from 0.399% to 0.052%.

[0029] (2) 2-Cyano-2-propvaleric acid was prepared by the ethyl 2-cyanoacetate method; 2-cyano-2-ethylpentanoic acid and 2-cyanopentanoic acid were separated from the crude 2-cyano-2-propvaleric acid by pulping, and 2-cyano-2-propvaleric acid monohydrate was obtained by purification; the content of 2-cyano-2-ethylpentanoic acid impurities decreased from 0.236% to 0.031%.

[0030] (3) 2-Cyano-2-propvaleric acid crude product was prepared by methyl 2-cyanoacetate method, and 2-cyano-2-methylvaleric acid was recovered by pulping, gradient crystallization, filtration and low temperature vacuum drying.

[0031] (4) Application of 2-cyano-2-methylvaleric acid and its monohydrate in the preparation of fragrance 2-methylvaleric acid (dihydrostrawberry acid); turning waste into treasure. Attached Figure Description

[0032] Figure 1 The high-performance liquid chromatogram of crude 2-cyano-2-propanolic acid prepared by the methyl cyanoacetate method in Example 11 is shown.

[0033] Figure 2 The high-performance liquid chromatogram of 2-cyano-2-propvaleric acid monohydrate prepared by the methyl cyanoacetate method in Example 11 is shown.

[0034] Figure 3 Example 22: High performance liquid chromatogram of crude 2-cyano-2-propanolic acid prepared by the ethyl cyanoacetate method;

[0035] Figure 4 The high-performance liquid chromatogram of 2-cyano-2-propanolic acid monohydrate prepared by the ethyl cyanoacetate method in Example 22 is shown. Detailed Implementation

[0036] The present invention will be further described in detail below with reference to the embodiments.

[0037] The method for recovering 2-cyano-2-methylvaleric acid (purification of 2-cyano-2-propvaleric acid) involves the following steps: Methyl 2-cyanoacetate and 1-chloropropane are reacted with potassium carbonate and catalytically dipropylated to obtain 2-cyano-2-propvaleric acid ester. Methyl 2-cyano-2-propvaleric acid ester is then hydrolyzed to prepare crude 2-cyano-2-propvaleric acid (Formula III). A polar solvent is added to the crude 2-cyano-2-propvaleric acid, followed by slurrying, gradient crystallization, filtration, and low-temperature vacuum drying to obtain 2-cyano-2-propvaleric acid monohydrate and 2-cyano-2-methylvaleric acid monohydrate.

[0038]

[0039] The method for separating 2-cyano-2-ethylpentanoic acid (purification of 2-cyano-2-propanolanoic acid) involves the following steps: Ethyl 2-cyanoacetate and 1-chloropropane are reacted with potassium carbonate and catalytically dipropylated to yield ethyl 2-cyano-2-propanolanoate. Ethyl 2-cyano-2-propanolanoate is then hydrolyzed to prepare crude 2-cyano-2-propanolanoic acid (Formula III). The crude 2-cyano-2-propanolanoic acid is then slurried with a polar solvent, subjected to gradient crystallization, filtered, and dried under low-temperature vacuum to obtain 2-cyano-2-propanolanoic acid monohydrate.

[0040]

[0041] The method for recovering 2-cyano-2-methylpentanoic acid involves using a pulping temperature selected from 30℃ to 60℃; a polar solvent selected from water, alcohol, or mixtures thereof; and an alcohol selected from methanol, ethanol, C3-C6 straight-chain or C3-C6 branched monohydric alcohols, ethylene glycol, C3-C5 straight-chain diols, or C4-C5 branched diols.

[0042] The method for separating 2-cyano-2-ethylpentanoic acid (purification of 2-cyano-2-propanolanoic acid) involves using a pulping temperature selected from 30℃ to 60℃; a polar solvent selected from water, alcohol, or mixtures thereof; and an alcohol selected from methanol, ethanol, C3-C6 straight-chain or C3-C6 branched monohydric alcohols, ethylene glycol, C3-C5 straight-chain diols, or C4-C5 branched diols.

[0043] A method for the recovery of 2-cyano-2-methylvaleric acid (purification of 2-cyano-2-propvaleric acid), 2-cyano-2-methylvaleric acid, represented by Formula I, is a precursor compound of 2-methylvaleric acid. The precursor compound of 2-methylvaleric acid—2-cyano-2-methylvaleric acid—was found using retrosynthetic analysis, specifically through FGI substitution of the reverse functional group and FGA addition of the reverse functional group.

[0044]

[0045] Separation of 2-cyano-2-ethylpentanoic acid (purification of 2-cyano-2-propanolanoic acid), a precursor compound of 2-ethylpentanoic acid; using retrosynthetic analysis, specifically FGI for reverse functional group exchange and FGA for reverse functional group addition, the precursor compound of 2-ethylpentanoic acid—2-cyano-2-ethylpentanoic acid—was identified.

[0046]

[0047] Methods for the recovery of 2-cyano-2-methylvaleric acid (purification of 2-cyano-2-propvaleric acid): 2-cyano-2-methylvaleric acid reacts with water to form 2-cyano-2-methylvaleric acid monohydrate; 2-cyano-2-propvaleric acid reacts with water to form 2-cyano-2-propvaleric acid monohydrate.

[0048]

[0049] Methods for the separation (purification) of 2-cyano-2-ethylpentanoic acid: 2-cyano-2-ethylpentanoic acid reacts with water to form 2-cyano-2-ethylpentanoic acid monohydrate; 2-cyano-2-pentanoic acid reacts with water to form 2-cyano-2-pentanoic acid monohydrate.

[0050]

[0051] A method for preparing 2-methylpentanoic acid of formula L, wherein 2-cyano-2-methylpentanoic acid of formula I is decarboxylated and hydrolyzed to obtain 2-methylpentanoic acid of formula L; L is also known as dihydrostrawberry acid, which is used to prepare fragrances.

[0052]

[0053] Example 1

[0054] Preparation of 2-cyano-2-propvaleric acid and recovery of 2-cyano-2-methylvaleric acid

[0055] (1) 0.2 mol methyl 2-cyanoacetate, 6.0 mmol tetramethylammonium bromide, 0.4 mol potassium carbonate (300 mesh), 100 ml DMF, 0.6 mol 1-chloropropane; under stirring, the oil bath temperature was set to 75℃ and the reaction was carried out for 2 h. The color of the reaction solution slowly darkened. Then the reaction was carried out at 95℃ for 3 h with stirring. After the reaction was completed, the temperature was lowered to below 45℃ and filtered. The filter cake was an inorganic salt. The filtrate was vacuum distilled to recover DMF and obtain a colorless and transparent liquid 1.

[0056] (2) Add 50 mL of methanol to the inorganic salt, stir and slurry at 50 °C, repeat three times, filter to recover the inorganic salt, and combine the filtrate with the transparent liquid 1 in (1); add alkali for hydrolysis, then add hydrochloric acid to acidify to pH 1.5, cool, crystallize, and filter to obtain crude 2-cyano-2-propanolic acid; take a sample for HPLC detection, and the results are as follows. Figure 1 As shown in Table 1.

[0057] Table 1. HPLC Detection Results of Crude Cyano-2-Propvalic Acid

[0058] Peak Retention time / minute RRT area / % area Altitude / microvolt Theoretical number of plates Resolution 1 6.047 0.28 0.094 4610 323 4098 -- 2 9.714 0.44 0.570 28100 1785 8595 9.2 3 10.981 0.50 0.399 19676 1360 12861 3.1 4 20.815 0.95 0.131 6459 528 65929 27.6 5 21.244 0.97 0.064 3157 384 147472 1.6 6 21.835 1.00 98.172 4837734 459309 95629 2.3 7 22.936 1.05 0.130 6428 777 172469 4.4 8 23.855 1.09 0.164 8060 867 166022 4.0 9 25.070 1.15 0.022 1095 140 221648 5.4 10 29.003 1.33 0.026 1280 165 296330 18.5 11 30.967 1.42 0.227 11200 1470 374795 9.5 total 100.000 4927800 467108

[0059] Peak 2, RRT = 0.44, 2-cyanopentanoic acid, 0.570%; Peak 3, RRT = 0.50, 2-cyano-2-methylpentanoic acid, 0.399%; Peak 5, RRT = 0.95, 2-cyano-2-isopropanolanoic acid, 0.131%; Peak 6, RRT = 1.00, 2-cyano-2-propanolanoic acid, 98.172%.

[0060] (3) Water was added to the crude 2-cyano-2-propvaleric acid and slurryed. The mixture was filtered, and the filter cake was dried under low temperature and vacuum to obtain 2-cyano-2-propvaleric acid monohydrate with a melting point of 49-50℃. Samples were taken for HPLC analysis, and the results are as follows: Figure 2 As shown in Table 2.

[0061]

[0062] Table 22 HPLC Detection Results of 2-Cyano-2-Propvallic Acid

[0063] Peak Retention time / minute RRT area / % area Altitude / microvolt Theoretical number of plates Resolution 1 11.040 0.50 0.052 2787 246 14297 -- 2 21.124 0.95 0.094 5071 568 125433 33.18 3 22.202 1.00 99.735 5355532 488387 83820 3.95 4 25.173 1.13 0.030 1630 252 312977 12.21 5 25.978 1.17 0.047 2512 353 299641 4.36 6 37.094 1.67 0.041 2215 336 553332 57.11 total 100.000 5369747 490143

[0064] Peak 1: RRT = 0.50, 2-cyano-2-methylvaleric acid, 0.052%; Peak 2: RRT = 0.95, 2-cyano-2-isopropanolic acid, 0.094%; Peak 3: RRT = 1.00, 2-cyano-2-propanolic acid, 99.735%.

[0065] Table 3 shows a comparison of the impurity content of crude and refined 2-cyano-2-propanolic acid prepared by the methyl 2-cyanoacetate method, as determined by HPLC.

[0066] Table 32. Impurity content of crude / refined 2-cyano-2-propanol acid prepared by the methyl cyanoacetate method.

[0067]

[0068] ND: Not detected.

[0069] The crude 2-cyano-2-propvaleric acid prepared by the methyl 2-cyanoacetate method was purified to a high-quality product from which 2-cyanopentanoic acid was obtained, and the content of 2-cyano-2-methylvaleric acid impurity decreased from 0.399% to 0.052%.

[0070] (4) Combine the filtrates obtained from multiple batches in step (3), evaporate part of the solvent water, perform gradient crystallization (below 10°C), filter, and dry the filter cake under low temperature vacuum to obtain 2-cyano-2-methylpentanoic acid (I) monohydrate.

[0071]

[0072] Example 2

[0073] Preparation and purification of 2-cyano-2-propvaleric acid

[0074] (1) 0.2 mol ethyl 2-cyanoacetate, 6.0 mmol tetraethylammonium bromide, 0.4 mol potassium carbonate (300 mesh), 100 ml DMF, and 0.6 mol 1-chloropropane were stirred at 85 °C for 2 h, then the temperature was raised to 100 °C and stirred for 3 h (LC monitoring of the reaction endpoint). After the reaction was completed, the temperature was lowered to below 45 °C, the inorganic salts were filtered off, and the DMF was recovered by vacuum distillation of the filtrate to obtain a colorless and transparent liquid 2 (ethyl 2-cyano-2-propanolate).

[0075] (2) Add 50 mL of ethanol to the inorganic salt, stir and beat at 50 °C for three times, filter to recover the inorganic salt, and combine the filtrate with the transparent liquid 2 in (1); add alkali to hydrolyze and then add hydrochloric acid to acidify to pH 1.5, cool, crystallize, and filter to obtain crude 2-cyano-2-propanolic acid; take a sample for HPLC detection, and the results are as follows. Figure 3 As shown in Table 4.

[0076] Table 4. HPLC Detection Results of Crude 2-Cyano-2-Propvalic Acid

[0077] Peak Retention time / minute RRT area / % area Altitude / microvolt Theoretical number of plates Resolution 1 9.464 0.44 0.090 4592 254 6145 -- 2 15.955 0.74 0.236 12093 721 20116 13.92 3 20.066 0.93 0.077 3949 310 56658 10.44 4 20.574 0.95 0.039 1999 199 88426 1.65 5 21.663 1.00 99.485 5087811 418387 69063 3.59 6 24.574 1.13 0.051 2589 318 184925 10.43 7 27.036 1.25 0.022 1113 139 255693 11.13 total 100.000 5114146 420328

[0078] Peak 1, RRT = 0.44, 2-cyanopentanoic acid, 0.090%; Peak 2, RRT = 0.74, 2-cyano-2-ethylpentanoic acid, 0.236%; Peak 4, RRT = 0.95, 2-cyano-2-isopropanolanoic acid, 0.039%; Peak 5, RRT = 1.00, 2-cyano-2-propanolanoic acid, 99.485%.

[0079] (3) Water was added to the crude 2-cyano-2-propvaleric acid and slurryed. The mixture was filtered, and the filter cake was dried under low temperature and vacuum to obtain 2-cyano-2-propvaleric acid monohydrate with a melting point of 49–50 °C. Samples were taken for HPLC analysis, and the results are as follows: Figure 4 As shown in Table 5.

[0080]

[0081] Table 5. HPLC Detection Results of Refined 2-Cyano-2-Propvallic Acid

[0082] Peak Retention time / minute RRT area / % area Altitude / microvolt Theoretical number of plates Resolution 1 15.677 0.73 0.031 1549 90 20851 -- 2 20.423 0.95 0.051 2570 273 91908 13.49 3 21.449 1.00 99.918 5042036 391466 59396 3.30 total 100.000 5046155 391828

[0083] Peak 1, RRT = 0.73, 2-cyano-2-ethylpentanoic acid, 0.031%; Peak 2, RRT = 0.95, 2-cyano-2-isopropanolanoic acid, 0.051%; Peak 3, RRT = 1.00, 2-cyano-2-propanolanoic acid, 99.918%.

[0084] Table 6 shows a comparison of the HPLC impurity content of crude and refined 2-cyano-2-propanolic acid prepared by the ethyl 2-cyanoacetate method.

[0085] Table 6. Impurity content of crude / refined 2-cyano-2-propanolic acid prepared by the ethyl 2-cyanoacetate method.

[0086]

[0087] ND: Not detected.

[0088] The crude 2-cyano-2-propvaleric acid prepared by the ethyl 2-cyanoacetate method was purified and no 2-cyanopentonic acid was detected in the purified product; the content of 2-cyano-2-ethylpentanoic acid impurity decreased from 0.236% to 0.031%.

[0089] Example 3

[0090] Preparation of valproic acid

[0091] 2-Cyano-2-propvalic acid or its monohydrate is prepared by sulfuric acid-catalyzed hydrolysis as described in Indian Patent [IN486MU2014A, 2015-09-25]. Decarboxylation of 2-cyano-2-propvalic acid or its monohydrate yields high-purity valvalic acid with a GC purity of not less than 99.90%.

[0092] Example 4

[0093] Preparation of 2-methylvaleric acid

[0094] 2-Cyano-2-methylvaleric acid or its monohydrate may be prepared by sulfuric acid-catalyzed hydrolysis as described in Indian Patent [IN486MU2014A, 2015-09-25].

[0095]

[0096] In this specification, the invention has been described with reference to specific embodiments thereof. However, it will be apparent that various modifications and variations can be made without departing from the spirit and scope of the invention. Therefore, this specification should be considered illustrative rather than restrictive.

Claims

1. A method for recovering 2-cyano-2-methylpentanoic acid as shown in chemical structural formula I, characterized in that... 2-cyanoacetic acid methyl ester and 1-chloropropane, under the action of potassium carbonate, catalytic dipropylization to prepare 2-cyano-2-propylvaleric acid methyl ester; 2-cyano-2-propylvaleric acid methyl ester hydrolysis to prepare 2-cyano-2-propylvaleric acid crude product shown in formula III; in 2-cyano-2-propylvaleric acid crude product, polar solvent is added to be beaten, gradient crystallization, filtration and low temperature vacuum drying to obtain 2-cyano-2-propylvaleric acid monohydrate and 2-cyano-2-methylvaleric acid monohydrate; 2-cyanopentanoic acid is separated and removed at the same time: 2-cyano-2-propylvaleric acid monohydrate decarboxylation and hydrolysis to obtain high purity propionic acid, GC purity is not less than 99.90%.

2. A method for isolating 2-cyano-2-ethylpentanoic acid represented by the chemical structural formula II, characterized in that 2-cyanoacetic acid methyl ester and 1-chloropropane, under the action of potassium carbonate, catalytic dipropylization to prepare 2-cyano-2-propylvaleric acid methyl ester; 2-cyano-2-propylvaleric acid methyl ester hydrolysis to prepare 2-cyano-2-propylvaleric acid crude product shown in formula III; in 2-cyano-2-propylvaleric acid crude product, polar solvent is added to be beaten, gradient crystallization, filtration and low temperature vacuum drying to obtain 2-cyano-2-propylvaleric acid monohydrate; 2-cyanopentanoic acid and 2-cyano-2-ethylvaleric acid are separated and removed: 2-cyano-2-propylvaleric acid monohydrate decarboxylation and hydrolysis to obtain high purity propionic acid, GC purity is not less than 99.90%.

3. The method of claim 1 or 2, wherein the beating temperature is selected from 30-60℃.

4. The method of claim 1 or 2, wherein The polar solvent is selected from water, alcohol or mixture thereof.

5. The method of claim 4, wherein The alcohol is selected from methanol, ethanol, C3-C6 straight chain or C3-C6 branched chain monohydric alcohol, ethylene glycol, C3-C5 straight chain dihydric alcohol or C4-C5 branched chain dihydric alcohol.

6. The recovery process of 2-cyano-2-methylpentanoic acid according to claim 1, characterized by The 2-cyano-2-methylvaleric acid shown in formula I is a precursor compound of 2-methylvaleric acid shown in formula L; the 2-cyano-2-methylvaleric acid, a precursor compound of 2-methylvaleric acid, is found by reverse functional group exchange FGI and reverse functional group addition FGA in reverse synthesis analysis:

7. The process of claim 2 for the isolation of 2-cyano-2-ethylpentanoic acid of the formula II ###0002### characterized in that The 2-cyano-2-ethylvaleric acid shown in formula II is a precursor compound of 2-ethylvaleric acid shown in formula B; the 2-cyano-2-ethylvaleric acid, a precursor compound of 2-ethylvaleric acid, is found by reverse functional group exchange FGI and reverse functional group addition FGA in reverse synthesis analysis:

8. The recovery process of 2-cyano-2-methylpentanoic acid according to claim 1, characterized by The 2-cyano-2-methylvaleric acid forms 2-cyano-2-methylvaleric acid monohydrate with water; 2-cyano-2-propylvaleric acid forms 2-cyano-2-propylvaleric acid monohydrate with water:

9. The process of claim 2 wherein the 2-cyano-2-ethylpentanoic acid is isolated by The 2-cyano-2-ethylvaleric acid forms 2-cyano-2-ethylvaleric acid monohydrate with water; 2-cyano-2-propylvaleric acid forms 2-cyano-2-propylvaleric acid monohydrate with water:

10. A method for producing 2-methylpentanoic acid represented by the following formula L, characterized by ###00003### L The 2-cyano-2-methylvaleric acid shown in formula I is decarboxylated and hydrolyzed to obtain the 2-methylvaleric acid: The 2-methylvaleric acid L, also known as dihydrofragrant acid, is used for preparing essence.

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