Preparation method of adipic acid derivative

Abstract

The invention discloses a preparation method of an adipic acid derivative, and relates to the technical field of chemical synthesis of adipic acid derivatives. The invention particularly discloses a method for preparing an adipic acid derivative by catalyzing acrylic ester with similar polarity through cobalt. The method comprises the following two steps: (1) in an inert atmosphere, mixing acrylate shown in a formula I, 2-alkyl acrylate shown in a formula II, a cobalt catalyst, alkali and a reducing agent in an organic solvent, and reacting under the illumination condition with the wavelength of 365-455nm at the temperature of 25-75 DEG C, so as to prepare alkenylated adipate; and (2) further hydrogenating the reaction product to obtain the adipic acid derivative. According to the preparation method, acrylic ester which is wide in source and low in price is used as a starting raw material, and a series of adipic acid derivatives with high additional value can be efficiently synthesized through the preparation method.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of chemical synthesis of adipic acid derivatives, in particular to a preparation method of adipic acid derivatives. BACKGROUND

[0002] Adipic acid derivatives have important applications in the chemical industry, such as in the synthesis of high-performance polymers, plasticizers, lubricants, etc. Traditional methods for preparing adipic acid derivatives have many drawbacks. For example, using cyclohexane as a raw material to prepare adipic acid through multi-step oxidation requires the use of a large amount of strong oxidizing agent, generating a large amount of pollutants such as nitrogen oxides; and the reaction conditions are harsh and the energy consumption is high. For example, using the cyanation method of butadiene, the electrolytic hydrogenation dimerization method of acrylonitrile, and the reductive amination method of adipic acid to prepare adiponitrile (an important precursor of adipic acid derivatives) has safety hazards such as toxic or explosive raw materials, high temperature and high pressure operation, and complex process flow. For example, using propenoate as a raw material and hydrogen as a reducing agent to perform a reductive coupling reaction under transition metal catalysis to prepare adipic acid ester also complicates the process flow due to the use of explosive gas.

[0003] Through the selective addition of transition metal catalysis to different propenoates, a potential effective route for preparing adipic acid derivatives is provided. However, the current field still faces many challenges, such as poor reaction selectivity, high catalyst cost, and harsh reaction conditions.

[0004] Therefore, it is of great practical significance to develop a method for efficiently, mildly, and selectively preparing adipic acid derivatives. SUMMARY

[0005] The present application provides a preparation method of adipic acid derivatives. This method uses cobalt to catalyze the addition of propenoates with similar polarity to prepare adipic acid derivatives, solving the problems of harsh reaction conditions, high pollution, and poor selectivity, and achieving efficient, green, and selective synthesis of adipic acid derivatives. The method is implemented through the following techniques.

[0006] The present application provides a method for preparing adipic acid derivatives by cobalt catalysis of propenoates with similar polarity, which includes the following steps:

[0007] In an inert atmosphere, propenoate of formula I, 2-alkyl propenoate of formula II, cobalt catalyst, base, and reducing agent are mixed in an organic solvent, and alkenylated adipate of formula III is prepared under irradiation of light with a wavelength of 365 nm-455 nm, as shown in the following reaction formula:

[0008] ;

[0009] The alkenylated adipate of formula III and Pd / C are mixed in methanol, hydrogen is introduced, and a hydrogenation reaction is performed to obtain adipic acid derivatives of formula IV, as shown in the following reaction formula:

[0010] ;

[0011] wherein, the group R 1 , R 2 and R 3 are independently selected from one of hydrogen, aliphatic chain, benzyl, aromatic group, aromatic heterocyclic group.

[0012] Optionally, in the preparation method of the adipic acid derivative, the hydrogenation reaction is carried out by dissolving the alkenyl adipate of formula III and palladium-carbon (Pd / C) with a molar ratio of 1:0.1 in MeOH solution under hydrogen condition at 35°C for 4-8 h.

[0013] Further, the chemical structure of the cobalt catalyst is:

[0014] ;

[0015] wherein, the group R 4 is one of halogen, alkyl; L is one of pyridine, imidazole, aniline, phenylethylamine, butylamine, isobutylamine.

[0016] Further, the chemical structure of the cobalt catalyst is:

[0017] .

[0018] Further, the reducing agent is at least one of zinc powder, aluminum powder, manganese powder, magnesium powder. Further, the reducing agent is zinc powder.

[0019] Further, the base is at least one of 2-tert-butyl-1,1,3,3-tetramethylguanidine (BTMG), tetramethylguanidine (TMG), triethylamine (Et3N). Further, the base is 2-tert-butyl-1,1,3,3-tetramethylguanidine (BTMG).

[0020] Further, the organic solvent is at least one of fluorobenzene, chlorobenzene, trifluorotoluene, toluene, furan, acetonitrile, ethyl acetate, dichloromethane, methanol. Further, the organic solvent is chlorobenzene. Further, the aliphatic chain is one of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, hexyl, heptyl, octyl, dodecyl. Further, the aromatic group is one of phenyl, naphthyl, fused ring aryl. Further, the aromatic heterocyclic group is selected from one of furanyl, pyridyl, thienyl, pyrrolyl, benzoxazolyl, benzofuranyl, isoquinolyl, quinolyl.

[0021] Further, the acrylic ester of formula I is any one of the following chemical structures:

[0022] ; where group R 5 For Me, OMe, t Bu (tert-butyl), F, Cl, Br, I, CF3.

[0023] Furthermore, the 2-alkyl acrylate represented by Formula II is selected from one of the following structures:

[0024] ; group R 5 For Me, OMe, t One of Bu, F, Cl, Br, I, CF3, R 6 It can be Ph (phenyl) or Bn (benzyl).

[0025] Optionally, the 2-alkyl acrylate is any one of the following chemical structural formulas:

[0026]

[0027] Furthermore, in preparing the adipic acid derivative, the molar ratio of the reducing agent to the acrylate shown in Formula I is (1-3):1. Even further, in preparing the adipic acid derivative, the molar ratio of the reducing agent (e.g., zinc powder) to the acrylate shown in Formula I is (1-2):1.

[0028] Furthermore, in preparing the adipic acid derivative, the ratio of the base to the acrylate represented by Formula I is (0.4-1):1. Even further, the molar ratio of the base (e.g., BTMG) to the acrylate represented by Formula I is (0.4-0.8):1.

[0029] Further, the molar ratio of acrylate I to the 2-alkyl acrylate shown in Formula II is 1:(2-5). Even further, the molar ratio of the acrylate shown in Formula I to the 2-alkyl acrylate shown in Formula II is 1:(3-5).

[0030] Furthermore, the reaction temperature for preparing the alkenyl adipate of formula III is 25-75°C. Even further, the reaction temperature is 30-45°C.

[0031] Compared with the prior art, the advantages of the present invention are:

[0032] This invention utilizes acrylates, a bulk chemical, as raw materials. Through cobalt catalysis, it achieves regioselective cross-addition between acrylates with similar polarities, efficiently preparing branched adipic acid derivatives. Previous methods could not selectively prepare branched asymmetric adipic acid derivatives. Furthermore, this invention features mild reaction conditions, a broad substrate range, and high functional group compatibility. The resulting target product is advantageous for further conversion into complex functional molecules, such as precursors for novel polyurethanes, polyamides, and other polymer materials. Attached Figure Description

[0033] Figure 1 The reaction mechanism diagram of the method for preparing adipic acid derivatives from cobalt-catalyzed acrylates with similar polarity provided by the present invention is shown.

[0034] Figure 2 This is the hydrogen nuclear magnetic resonance spectrum of Example 1.

[0035] Figure 3 This is the carbon NMR spectrum of Example 1. Detailed Implementation

[0036] The technical solution of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0037] In some embodiments of the present invention, such as Figure 1 As shown, the method for preparing adipate using a cobalt catalyst includes the following steps:

[0038] (1) Under an inert atmosphere (such as argon, nitrogen, etc.), the acrylate of Formula I, the 2-alkyl acrylate of Formula II, the cobalt catalyst, the reducing agent, and the base are mixed in an organic solvent and the alkenyl adipate of Formula III is prepared by irradiation with light of wavelength 365 nm-455 nm.

[0039] (2) The alkenyl adipate of formula III and Pd / C of the above reaction product are mixed in methanol and hydrogen (H2) is introduced for further hydrogenation to obtain the adipate derivative of formula IV.

[0040] In other embodiments of the present invention, the reaction process for preparing adipic acid derivatives is as follows:

[0041] .

[0042] In the above-mentioned method for preparing adipic acid derivatives, the group R 1 R 2 and R 3Each group is independently selected from one of hydrogen, aliphatic chain group, benzyl group, aromatic group, and aromatic heterocyclic group.

[0043] Optionally, in the above-mentioned preparation method of adipic acid derivative, the specific method of hydrogenation reaction is as follows: under hydrogen conditions, Formula III and palladium on carbon (Pd / C) are dissolved in MeOH solution at a molar ratio of 1:0.1, and the reaction is carried out at 35°C for 4-8 h.

[0044] Optionally, the aliphatic chain group can be selected from any one of methyl, ethyl, (iso)propyl, (iso)butyl, pentyl, hexyl, heptyl, octyl, and dodecyl. Optionally, the aromatic group is one of phenyl, naphthyl, and fused-ring aryl. Optionally, the aromatic heterocyclic group is selected from one of furanyl, pyridinyl, thiophene, pyrroleyl, benzoxazolyl, benzofuranyl, isoquinolinyl, and quinolinyl.

[0045] The chemical structure of the cobalt catalyst is as follows:

[0046] ;

[0047] Wherein, group R is one of halogen or alkyl; L is one of pyridine, imidazole, aniline, phenethylamine, butylamine, or isobutylamine.

[0048] Specifically, the chemical structure of the cobalt catalyst is as follows:

[0049]

[0050] Optionally, the reducing agent is at least one selected from zinc powder, aluminum powder, manganese powder, and magnesium powder. Specifically, the reducing agent is zinc powder.

[0051] Optionally, the base is at least one selected from 2-tert-butyl-1,1,3,3-tetramethylguanidine (BTMG), tetramethylguanidine (TMG), and triethylamine (Et3N). Specifically, the base is 2-tert-butyl-1,1,3,3-tetramethylguanidine (BTMG).

[0052] Optionally, the organic solvent is at least one selected from fluorobenzene, chlorobenzene, trifluorotoluene, toluene, furan, acetonitrile, ethyl acetate, dichloromethane, and methanol. Specifically, the solvent is chlorobenzene.

[0053] The acrylate represented by Formula I is any one of the following chemical structural formulas:

[0054] ; where the group R 5 For Me, OMe, t One of Bu, F, Cl, Br, I, and CF3.

[0055] The 2-alkyl acrylate represented by Formula II is any one of the following chemical structural formulas:

[0056] ; group R 5 For Me, OMe, t One of Bu, F, Cl, Br, I, CF3, R 6 It can be Ph or Bn.

[0057] Furthermore, in preparing the adipic ester, the molar ratio of the reducing agent to the acrylate shown in Formula I is (1-3):1. Even further, in preparing the adipic ester, the molar ratio of the reducing agent (e.g., zinc powder) to the acrylate shown in Formula I is (1-2):1.

[0058] Furthermore, in preparing the adipate ester, the molar ratio of the base to the acrylate represented by Formula I is (0.4-1):1. Even further, the molar ratio of the base (e.g., BTMG) to the acrylate represented by Formula I is (0.4-0.8):1.

[0059] Further, the molar ratio of the acrylate shown in Formula I to the 2-alkyl acrylate shown in Formula II is 1:(2-5). Even further, the molar ratio of the acrylate shown in Formula I to the 2-alkyl acrylate shown in Formula II is 1:(3-5).

[0060] Furthermore, the reaction temperature for preparing the alkenyl adipate of Formula III is 25-75°C. Even further, the reaction temperature is 30-45°C.

[0061] In the following specific implementation cases, all materials used are commercially available products purchased from the market.

[0062] Example 1: Preparation of 6-methoxy-5-methyl-6-oxohexanoic acid

[0063] The preparation process of 6-methoxy-5-methyl-6-oxohexanoic acid is shown in the following formula.

[0064] .

[0065] The specific preparation process is as follows:

[0066] (1) In an argon atmosphere, cobalt catalyst (4.4 mg, 10 mol%), zinc powder (13.0 mg, 0.2 mmol, 2.0 equiv), benzyl acrylate (16.2 mg, 0.1 mmol, 1.0 equiv), and methyl 2-methacrylate (50.1 mg, 0.5 mmol, 5.0 equiv) were added to the reaction flask; then 0.5 mL of chlorobenzene was added to dissolve and mix the reactants, and finally BTMG (6.9 mg, 40 mol%) was added.

[0067] (2) The reaction mixture was placed under 455 nm LEDs and stirred at room temperature for 24 h; the mixture was washed with ethyl acetate and transferred to a flask, and the volatiles were removed under vacuum to obtain the residue.

[0068] (3) The residue was purified by silica gel column chromatography using a mixture of petroleum ether and ethyl acetate as the eluent to obtain a colorless, oily alkenylated adipate ester (22.5 mg, yield 86%). The product's R-value was determined using petroleum ether-ethyl acetate as the developing solvent (volume ratio of petroleum ether to ethyl acetate 20:1) on a silica gel thin-layer plate. f = 0.3.

[0069] (4) The above product was placed into a 25 mL reaction tube, and Pd / C (2.3 mg, 10 mol%) and 1 mL MeOH were added to mix the reactants. Then hydrogen gas was introduced and the reaction was carried out at 35 °C for 4 h. After the reaction was completed, the mixture was filtered directly and evaporated to dryness to obtain a colorless oily product, 6-methoxy-5-methyl-6-oxohexanoic acid (12.9 mg, yield 86%).

[0070] like Figure 2 , 3 As shown, the structural characterization data of the product are as follows:

[0071] 1 H NMR (400 MHz, CDCl3, 23 ºC, δ): 3.61 (s, 3H), 2.44 – 2.36 (m, 1H), 2.33 – 2.24 (m, 2H), 1.70 – 1.52 (m, 3H), 1.46 – 1.36 (m, 1H), 1.10 (d, J =6.9 Hz, 3H) ppm.

[0072] 13C NMR (100 MHz, CDCl3, 23 ºC, δ): 179.54, 177.03, 51.79, 39.29, 33.92, 33.07, 22.45, 17.17 ppm.

[0073] HRMS-ESI(m / z) calc'd for C8H 15 O4 [M+H] + 175.0965; found, 175.0962.

[0074] Example 2: Preparation of 6-ethoxy-5-methyl-6-oxohexanoic acid

[0075] The preparation process of 6-ethoxy-5-methyl-6-oxohexanoic acid is as follows:

[0076] Steps (1) and (2) are essentially the same as in Example 1. The difference is that methyl methacrylate is replaced with ethyl 2-methacrylate (57.0 mg, 0.5 mmol, 5.0 equiv).

[0077] (3) The residue was purified by silica gel column chromatography using a mixture of petroleum ether and ethyl acetate as the eluent to obtain a colorless, oily alkenylated adipate ester (19.9 mg, yield 72%). The product's R-value was determined using petroleum ether-ethyl acetate as the developing solvent (volume ratio of petroleum ether to ethyl acetate 20:1) on a silica gel thin-layer plate. f = 0.3.

[0078] (4) The above-mentioned alkenylated adipate ester was placed into a 25 mL reaction tube, and Pd / C (2.0 mg, 10 mol%) and 1 mL MeOH were added to dissolve the mixture. Then hydrogen gas was introduced and the reaction was carried out at 35 °C for 4 h. After the reaction was completed, the mixture was directly filtered and evaporated to dryness to obtain the target product 6-ethoxy-5-methyl-6-oxohexanoic acid (12.2 mg, yield 90%).

[0079] The structural characterization data of the product are as follows:

[0080] 1H NMR (400 MHz, CDCl3, 23 ºC, δ): 4.15 (q, J = 7.1 Hz, 2H), 2.50 –2.42 (m, 1H), 2.38 (t, J = 7.2 Hz, 2H), 1.78 – 1.60 (m, 3H), 1.54 – 1.44 (m,1H), 1.27 (t, J = 7.1 Hz, 3H), 1.18 (d, J = 7.0 Hz, 3H) ppm.

[0081] 13 C NMR (100 MHz, CDCl3, 23 ºC, δ): 179.36, 176.59, 60.45, 39.41, 33.92, 33.10, 22.47, 17.19, 14.37 ppm.

[0082] HRMS-ESI(m / z) calc'd for C9H 17 O4 [M+H] + 189.1121; found, 189.1118.

[0083] Example 3: Preparation of 6-isobutoxy-5-methyl-6-oxohexanoic acid

[0084] The specific preparation process of 6-isobutoxy-5-methyl-6-oxohexanoic acid is as follows:

[0085] Steps (1) and (2) are essentially the same as in Example 1. The difference is that methyl methacrylate is replaced with isobutyl 2-methacrylate (71.0 mg, 0.5 mmol, 5.0 equiv).

[0086] (3) The residue was purified by silica gel rapid column chromatography with petroleum ether / ethyl acetate mixture as the eluent to obtain colorless oily alkenyl adipate (19.5 mg, yield 64%).

[0087] The R of the product was measured on a silica gel thin-layer plate using petroleum ether-ethyl acetate as the developing solvent (volume ratio of petroleum ether to ethyl acetate was 20:1). f = 0.3.

[0088] The alkenylated adipate of the above products was placed in a 25 mL reaction tube, and Pd / C (2.0 mg, 10 mol%) and 1 mL MeOH were added to dissolve the reactants. Hydrogen gas was then introduced, and the reaction was carried out at 35 °C for 4 h. After the reaction was complete, the mixture was directly filtered and evaporated to dryness to obtain the target product, 6-isobutoxy-5-methyl-6-oxohexanoic acid (13.7 mg, yield 99%).

[0089] The structural characterization data of the product are as follows:

[0090] 1 H NMR (400 MHz, CDCl3, 23 ºC, δ): 3.87 (d, J = 6.6 Hz, 2H), 2.51 –2.45 (m, 1H), 2.36 (t, J = 7.2 Hz, 2H), 2.00 – 1.89 (m, 1H), 1.76 – 1.61 (m,3H), 1.55 – 1.44 (m, 1H), 1.19 (d, J = 7.0 Hz, 3H), 0.95 (d, J = 6.8 Hz, 6H)ppm.

[0091] 13 C NMR (100 MHz, CDCl3, 23 ºC, δ): 179.12, 176.65, 70.62, 39.55, 34.14, 33.16, 27.89, 22.63, 19.23, 17.28 ppm.

[0092] HRMS-ESI(m / z) calc'd for C 11 H 21 O4 [M+H] + 217.1434; found, 217.1430.

[0093] Example 4: Preparation of 6-(tert-butoxy)-5-methyl-6-oxohexanoic acid

[0094] The preparation process of 6-(tert-butoxy)-5-methyl-6-oxohexanoic acid is as follows:

[0095] Steps (1) and (2) are essentially the same as in Example 1. The difference is that methyl methacrylate is replaced with tert-butyl 2-methacrylate (71.0 mg, 0.5 mmol, 5.0 equiv).

[0096] (3) The residue was purified by silica gel rapid column chromatography with petroleum ether / ethyl acetate mixture as the eluent to obtain colorless oily alkenyl adipate (19.5 mg, yield 64%).

[0097] The R of the product was measured on a silica gel thin-layer plate using petroleum ether-ethyl acetate as the developing solvent (volume ratio of petroleum ether to ethyl acetate was 20:1). f = 0.3.

[0098] The alkenylated adipate of the above products was placed in a 25 mL reaction tube, and Pd / C (2.0 mg, 10 mol%) and 1 mL MeOH were added to dissolve the mixture. Hydrogen gas was then introduced, and the reaction was carried out at 35 °C for 4 h. After the reaction was complete, the mixture was directly filtered and evaporated to dryness to obtain the target product 6-(tert-butoxy)-5-methyl-6-oxohexanoic acid (11.2 mg, yield 81%).

[0099] The structural characterization data of the product are as follows:

[0100] 1 H NMR (400 MHz, CDCl3, 23 ºC, δ): 2.42 – 2.28 (m, 3H), 1.73 – 1.59 (m, 3H), 1.50 – 1.39 (m, 10H), 1.13 (d, J = 7.0 Hz, 3H) ppm.

[0101] 13 C NMR (100 MHz, CDCl3, 23 ºC, δ): 179.23, 175.98, 80.23, 40.31, 33.97, 33.25, 28.21, 22.51, 17.28 ppm.

[0102] HRMS-ESI(m / z) calc'd for C 11 H 21 O4 [M+H] + 217.1434; found, 217.1429.

[0103] Example 5: Preparation of 6-(cyclopropylmethoxy)-5-methyl-6-oxohexanoic acid

[0104] The preparation process of 6-(cyclopropylmethoxy)-5-methyl-6-oxohexanoic acid is as follows:

[0105] Steps (1) and (2) are essentially the same as in Example 1. The difference is that methyl 2-methacrylate is replaced with cyclopropyl methacrylate (70.0 mg, 0.5 mmol, 5.0 equiv).

[0106] (3) The residue was purified by silica gel rapid column chromatography with petroleum ether / ethyl acetate mixture as the eluent to obtain colorless oily alkenyl adipate (18.7 mg, yield 62%).

[0107] The R of the product was measured on a silica gel thin-layer plate using petroleum ether-ethyl acetate as the developing solvent (volume ratio of petroleum ether to ethyl acetate was 20:1). f = 0.3.

[0108] The alkenylated adipate of the above products was placed in a 25 mL reaction tube, and Pd / C (1.9 mg, 10 mol%) and 1 mL MeOH were added to dissolve the reactants. Hydrogen gas was then introduced, and the reaction was carried out at 35 °C for 4 h. After the reaction was complete, the mixture was directly filtered and evaporated to dryness to obtain the target product 6-(cyclopropylmethoxy)-5-methyl-6-oxohexanoic acid (13.1 mg, yield 99%).

[0109] The structural characterization data of the product are as follows:

[0110] 1 H NMR (400 MHz, CDCl3, 23 ºC, δ): 3.93 (d, J = 7.4 Hz, 2H), 2.54 –2.44 (m, 1H), 2.38 (t, J = 7.2 Hz, 2H), 1.79 – 1.61 (m, 3H), 1.55 – 1.45 (m,1H), 1.19 (d, J = 7.0 Hz, 3H), 1.16 – 1.08 (m, 1H), 0.61 – 0.54 (m, 2H), 0.33 – 0.26 (m, 2H) ppm.

[0111] 13 C NMR (100 MHz, CDCl3, 23 ºC, δ): 179.20, 176.72, 69.21, 39.48, 33.95, 33.20, 22.51, 17.24, 9.99, 3.29 ppm.

[0112] HRMS-ESI(m / z) calc'd for C 11 H 19 O4 [M+H] +215.1278; found, 215.1274.

[0113] Example 6: Preparation of 5-methyl-6-(octane-2-oxy)-6-oxohexanoic acid

[0114] The preparation process of 5-methyl-6-(octane-2-oxy)-6-oxohexanoic acid is as follows:

[0115] Steps (1) and (2) are essentially the same as in Example 1. The difference is that methyl 2-methacrylate is replaced with octane-2-ylmethacrylate (99.1 mg, 0.5 mmol, 5.0 equiv).

[0116] (3) The residue was purified by silica gel rapid column chromatography with petroleum ether / ethyl acetate mixture as the eluent to obtain colorless oily alkenyl adipate (21.1 mg, yield 61%).

[0117] The R of the product was measured on a silica gel thin-layer plate using petroleum ether-ethyl acetate as the developing solvent (volume ratio of petroleum ether to ethyl acetate was 20:1). f = 0.3.

[0118] (4) The above-mentioned alkenylated adipate ester was placed into a 25 mL reaction tube, and Pd / C (2.1 mg, 10 mol%) and 1 mL MeOH were added to dissolve the mixture. Then hydrogen gas was introduced and the reaction was carried out at 35 °C for 4 h. After the reaction was completed, the mixture was directly filtered and evaporated to dryness to obtain the target product 5-methyl-6-(octane-2-oxy)-6-oxohexanoic acid (14.8 mg, yield 89%).

[0119] The structural characterization data of the product are as follows:

[0120] 1 H NMR (400 MHz, CDCl3, 23 ºC, δ): 4.96 – 4.87 (m, 1H), 2.50 – 2.30(m, 3H), 1.78 – 1.54 (m, 4H), 1.54 – 1.43 (m, 2H), 1.35 – 1.26 (m, 8H), 1.21(d, J = 6.3, 3H), 1.17 (d, J = 7.0 Hz, 3H), 0.89 (t, J = 6.7 Hz, 3H) ppm.

[0121] 13C NMR (100 MHz, CDCl3, 23 ºC, δ): 179.28, 176.24, 71.01, 39.74, 36.03, 33.94, 33.12, 31.87, 29.22, 25.50, 22.70, 22.50, 20.15, 17.31, 14.19ppm.

[0122] HRMS-ESI(m / z) calc'd for C 15 H 29 O4 [M+H] + 273.2060; found, 273.2054.

[0123] Example 7: Preparation of 6-((6-chlorohexyl)oxy)-5-methyl-6-oxohexanoic acid

[0124] The preparation process of 6-((6-chlorohexyl)oxy)-5-methyl-6-oxohexanoic acid is as follows:

[0125] Steps (1) and (2) are essentially the same as in Example 1. The difference is that methyl methacrylate is replaced with 6-chlorohexyl methacrylate (102.0 mg, 0.5 mmol, 5.0 equiv).

[0126] (3) The residue was purified by silica gel rapid column chromatography with petroleum ether / ethyl acetate mixture as the eluent to obtain colorless oily alkenyl adipate (22.0 mg, yield 60%).

[0127] The R of the product was measured on a silica gel thin-layer plate using petroleum ether-ethyl acetate as the developing solvent (volume ratio of petroleum ether to ethyl acetate was 20:1). f = 0.3.

[0128] (4) The above-mentioned alkenylated adipate ester was placed into a 25 mL reaction tube, and Pd / C (2.2 mg, 10 mol%) and 1 mL MeOH were added to dissolve the mixture. Then hydrogen gas was introduced and the reaction was carried out at 35 °C for 4 h. After the reaction was completed, the mixture was directly filtered and evaporated to dryness to obtain the target product 6-((6-chlorohexyl)oxy)-5-methyl-6-oxohexanoic acid (15.4 mg, yield 92%).

[0129] The structural characterization data of the product are as follows:

[0130] 1H NMR (400 MHz, CDCl3, 23 ºC, δ): 4.01 (t, J = 6.6 Hz, 2H), 3.46 (t,J = 6.7 Hz, 2H), 2.43 – 2.33 (m, 1H), 2.29 (t, J = 7.2 Hz, 2H), 1.76 – 1.68(m, 2H), 1.65 – 1.52 (m, 5H), 1.46 – 1.28 (m, 5H), 1.09 (d, J = 7.0 Hz, 3H)ppm.

[0131] 13 C NMR (100 MHz, CDCl3, 23 ºC, δ): 179.44, 176.60, 64.38, 45.04,39.46, 33.93, 33.11, 32.56, 28.62, 26.62, 25.40, 22.49, 17.21 ppm.

[0132] HRMS-ESI(m / z) calc'd for C 13 H 24 ClO4 [M+H] + 279.1358; found, 279.1352.

[0133] Example 8: Preparation of 5-methyl-6-oxo-6-((1,7,7-trimethylbicyclo[2.2.1]heptane-2-yl)oxy)hexanoic acid

[0134] The preparation process of 5-methyl-6-oxo-6-((1,7,7-trimethylbicyclo[2.2.1]heptane-2-yl)oxy)hexanoic acid is as follows:

[0135] Steps (1) and (2) are essentially the same as in Example 1. The difference is that methyl methacrylate is replaced with 1,7,7-trimethylbicyclo[2.2.1]heptane-2-yl methacrylate (111.1 mg, 0.5 mmol, 5.0 equiv).

[0136] (3) The residue was purified by silica gel rapid column chromatography with petroleum ether / ethyl acetate mixture as the eluent to obtain colorless oily alkenyl adipate (22.2 mg, yield 58%).

[0137] The R of the product was measured on a silica gel thin-layer plate using petroleum ether-ethyl acetate as the developing solvent (volume ratio of petroleum ether to ethyl acetate was 20:1). f = 0.3.

[0138] (4) The above-mentioned alkenyl adipate ester was placed into a 25 mL reaction tube, and Pd / C (2.2 mg, 10 mol%) and 1 mL MeOH were added to dissolve the mixed reactants. Then hydrogen gas was introduced and the reaction was carried out at 35 °C for 4 h. After the reaction was completed, the mixture was directly filtered and evaporated to dryness to obtain the target product 5-methyl-6-oxo-6-((1,7,7-trimethylbicyclo[2.2.1]heptane-2-yl)oxy)hexanoic acid (14.8 mg, yield 86%).

[0139] The structural characterization data of the product are as follows:

[0140] 1 H NMR (400 MHz, CDCl3, 23 ºC, δ): 4.93 – 4.88 (m, 1H), 2.55 – 2.44(m, 1H), 2.43 – 2.32 (m, 3H), 2.00 – 1.92 (m, 1H), 1.82 – 1.63 (m, 5H), 1.56– 1.46 (m, 1H), 1.38 – 1.23 (m, 2H), 1.19 (d, J = 7.0 Hz, 3H), 1.00 – 0.94(m, 1H), 0.93 (s, 3H), 0.89 (s, 3H), 0.85 (s, 3H)ppm.

[0141] 13 C NMR (100 MHz, CDCl3, 23 ºC, δ): 179.05, 176.77, 79.83, 48.93,47.97, 45.03, 39.75, 37.03, 33.93, 33.17, 28.18, 27.28, 22.53, 19.83, 18.99,17.36, 13.64 ppm.

[0142] HRMS-ESI(m / z) calc'd for C 17 H 29 O4 [M+H] + 297.2060; found, 297.2054.

[0143] Example 9: Preparation of 6-((2-isopropyl-5-methylcyclohexyl)oxy)-5-methyl-6-oxohexanoic acid

[0144] The preparation process of 6-((2-isopropyl-5-methylcyclohexyl)oxy)-5-methyl-6-oxohexanoic acid is as follows:

[0145] Steps (1) and (2) are essentially the same as in Example 1. The difference is that methyl methacrylate is replaced with 2-isopropyl-5-methylcyclohexyl methacrylate (112.1 mg, 0.5 mmol, 5.0 equiv).

[0146] (3) The residue was purified by silica gel rapid column chromatography with petroleum ether / ethyl acetate mixture as the eluent to obtain colorless oily alkenyl adipate (25.4 mg, yield 66%).

[0147] The R of the product was measured on a silica gel thin-layer plate using petroleum ether-ethyl acetate as the developing solvent (volume ratio of petroleum ether to ethyl acetate was 20:1). f = 0.3.

[0148] (4) The above-mentioned alkenylated adipate ester was placed into a 25 mL reaction tube, and Pd / C (2.3 mg, 10 mol%) and 1 mL MeOH were added to dissolve the mixture. Then hydrogen gas was introduced and the reaction was carried out at 35 °C for 4 h. After the reaction was completed, the mixture was directly filtered and evaporated to dryness to obtain the target product 6-((2-isopropyl-5-methylcyclohexyl)oxy)-5-methyl-6-oxohexanoic acid (16.3 mg, yield 83%).

[0149] The structural characterization data of the product are as follows:

[0150] 1 H NMR (400 MHz, CDCl3, 23 ºC, δ): 4.60 (td, J = 10.9, 4.3 Hz, 1H), 2.40 – 2.22 (m, 3H), 1.94 – 1.87 (m, 1H), 1.84 – 1.76 (m, 1H), 1.69 – 1.51(m, 5H), 1.47 – 1.27 (m, 3H), 1.08 (d, J = 7.0 Hz, 3H), 1.01 – 0.86 (m, 2H), 0.83 (dd, J = 6.9, 3.8 Hz, 6H), 0.80 – 0.74 (m, 1H), 0.68 (d, J = 7.0 Hz, 3H) ppm.

[0151] 13C NMR (100 MHz, CDCl3, 23 ºC, δ): 179.58, 176.12, 74.18, 47.15,41.02, 39.84, 34.42, 33.99, 33.16, 31.50, 26.32, 23.46, 22.14, 20.89, 17.31,16.25 ppm.

[0152] HRMS-ESI(m / z) calc'd for C 17 H 29 O4 [M+H] + 299.2216; found, 299.2211.

[0153] Example 10: Preparation of 6-methoxy-5-methyl-6-oxohexanoic acid

[0154] The preparation process of 6-methoxy-5-methyl-6-oxohexanoic acid is as follows:

[0155] Steps (1) and (2) are essentially the same as in Example 1. The difference is that benzyl acrylate is replaced with pyridine-3-methacrylate (16.3 mg, 0.1 mmol, 1.0 equiv).

[0156] (3) The residue was purified by silica gel rapid column chromatography with petroleum ether / ethyl acetate mixture as the eluent to obtain colorless oily alkenyl adipate (17.9 mg, yield 68%).

[0157] The R of the product was measured on a silica gel thin-layer plate using petroleum ether-ethyl acetate as the developing solvent (volume ratio of petroleum ether to ethyl acetate was 20:1). f = 0.3.

[0158] (4) The above-mentioned alkenylated adipate ester was placed into a 25 mL reaction tube, and Pd / C (2.0 mg, 10 mol%) and 1 mL MeOH were added to dissolve the mixture. Then hydrogen gas was introduced and the reaction was carried out at 35 °C for 4 h. After the reaction was completed, the mixture was directly filtered and evaporated to dryness to obtain the target product 6-methoxy-5-methyl-6-oxohexanoic acid (11.2 mg, yield 95%).

[0159] The structural characterization data of the product are as follows:

[0160] 1H NMR (400 MHz, CDCl3, 23 ºC, δ): 10.11 (s, 1H), 3.68 (s, 3H), 2.52 –2.42 (m, 1H), 2.33 (t, J = 7.2 Hz, 2H), 1.76 – 1.58 (m, 3H), 1.53 – 1.43 (m,1H), 1.17 (d, J = 7.0 Hz, 3H) ppm.

[0161] 13 C NMR (100 MHz, CDCl3, 23 ºC, δ): 179.12, 177.11, 51.71, 39.33, 34.51, 33.22, 22.76, 17.14 ppm.

[0162] HRMS-ESI(m / z) calc'd for C8H 15 O4 [M+H] + 175.0965; found, 175.0962.

[0163] Example 11: Preparation of 1-methyl-6-((2,2,7,7-tetramethyltetrahydro-5H-bis([1,3]dioxonol)[4,5-b:4',5'-d]pyran-5-yl)methyl)2-methyl adipate

[0164] The preparation process of 1-methyl-6-((2,2,7,7-tetramethyltetrahydro-5H-bis([1,3]dioxonol)[4,5-b:4',5'-d]pyran-5-yl)methyl)2-methyl adipate is as follows:

[0165] Steps (1) and (2) are essentially the same as in Example 1. The difference is that benzyl acrylate is replaced with (2,2,7,7-tetramethyltetrahydro-5H-bis([1,3]dioxonol)[4,5-b:4',5'-d]pyran-5-yl)methacrylate (31.4 mg, 0.1 mmol, 1.0 equiv).

[0166] (3) The residue was purified by silica gel rapid column chromatography with petroleum ether / ethyl acetate mixture as the eluent to obtain colorless oily alkenyl adipate (29.0 mg, yield 70%).

[0167] The R of the product was measured on a silica gel thin-layer plate using petroleum ether-ethyl acetate as the developing solvent (volume ratio of petroleum ether to ethyl acetate was 20:1). f = 0.3.

[0168] (4) The above-mentioned alkenylated adipate was placed in a 25 mL reaction tube, and Pd / C (2.9 mg, 10 mol%) and 1 mL MeOH were added to dissolve the mixed reactants. Then hydrogen gas was introduced and the reaction was carried out at 35 °C for 4 h. After the reaction was completed, the mixture was directly filtered and evaporated to dryness to obtain the target product 1-methyl-6-((2,2,7,7-tetramethyltetrahydro-5H-bis([1,3]dioxonol)[4,5-b:4',5'-d]pyran-5-yl)methyl)2-methyl adipate (27.7 mg, yield 95%).

[0169] The structural characterization data of the product are as follows:

[0170] 1 H NMR (400 MHz, CDCl3, 23 ºC, δ): 5.54 (d, J = 5.0 Hz, 1H), 4.62 (dd,J = 7.9, 2.5 Hz, 1H), 4.36 – 4.28 (m, 2H), 4.25 – 4.14 (m, 2H), 4.05 – 3.99(m, 1H), 3.67 (s, 3H), 2.50 – 2.41 (m, 1H), 2.35 (t, J = 7.1 Hz, 2H), 1.75 –1.54 (m, 4H), 1.51 (s, 3H), 1.45 (s, 3H), 1.33 (d, J = 3.8 Hz, 6H), 1.16 (d,J = 6.9 Hz, 3H) ppm.

[0171] 13 C NMR (100 MHz, CDCl3, 23 ºC, δ): 176.97, 173.33, 109.76, 108.86,96.43, 71.21, 70.85, 70.59, 66.12, 63.46, 51.64, 39.30, 34.08, 33.14, 26.12,26.07, 25.08, 24.61, 22.78, 17.11 ppm.

[0172] HRMS-ESI(m / z) calc'd for C 20 H 31 O9 [MH] + 415.1974; found, 415.1970.

[0173] Example 12: Preparation of 6-(5-(2,5-dimethylphenoxy)-2,2-dimethylpentyl)-1-methyl-2-methyl adipate

[0174] The preparation process of 6-(5-(2,5-dimethylphenoxy)-2,2-dimethylpentyl)-1-methyl-2-methyl adipate is as follows:

[0175] Steps (1) and (2) are essentially the same as in Example 1. The difference is that benzyl acrylate is replaced with 5-(2,5-dimethylphenoxy)-2,2-dimethylammonium acrylate (29.0 mg, 0.1 mmol, 1.0 equiv).

[0176] (3) The residue was purified by silica gel rapid column chromatography with petroleum ether / ethyl acetate mixture as the eluent to obtain colorless oily alkenyl adipate (24.6 mg, yield 63%).

[0177] The R of the product was measured on a silica gel thin-layer plate using petroleum ether-ethyl acetate as the developing solvent (volume ratio of petroleum ether to ethyl acetate was 20:1). f = 0.3.

[0178] (4) The above-mentioned alkenylated adipate was placed in a 25 mL reaction tube, and Pd / C (2.5 mg, 10 mol%) and 1 mL MeOH were added to dissolve the mixture. Then hydrogen gas was introduced and the reaction was carried out at 35 °C for 4 h. After the reaction was completed, the mixture was directly filtered and evaporated to dryness to obtain the target product 6-(5-(2,5-dimethylphenoxy)-2,2-dimethylpentyl)-1-methyl-2-methyl adipate (22.7 mg, yield 92%).

[0179] The structural characterization data of the product are as follows:

[0180] 1 H NMR (400 MHz, CDCl3, 23 ºC, δ): 7.02 (d, J = 7.4 Hz, 1H), 6.68 (d,J = 7.6 Hz, 1H), 6.64 (d, J = 1.6 Hz, 1H), 3.94 (t, J = 6.4 Hz, 2H), 3.86 (s,2H), 3.69 (s, 3H), 2.54 – 2.43 (m, 1H), 2.39 – 2.31 (m, 5H), 2.19 (s, 3H),1.85 – 1.61 (m, 5H), 1.53 – 1.43 (m, 3H), 1.18 (d, J = 7.0 Hz, 3H), 0.97 (s,6H) ppm.

[0181] 13 C NMR (100 MHz, CDCl3, 23 ºC, δ): 177.01, 173.57, 157.12, 136.59,130.41, 123.66, 120.79, 112.08, 72.36, 68.43, 51.70, 39.31, 35.54, 34.24,33.69, 33.26, 24.37, 24.23, 22.83, 21.54, 17.17, 15.89 ppm.

[0182] HRMS-ESI(m / z) calc'd for C 23 H 35 O5 [MH] + 391.2490; found, 391.2487.

[0183] Example 13: Preparation of 1-methyl-6-pentyl 2-methyl adipic acid

[0184] The preparation process of 1-methyl-6-pentyl 2-methyl adipic acid is as follows:

[0185] Steps (1) and (2) are essentially the same as in Example 1. The difference is that benzyl acrylate is replaced with amyl acrylate (14.2 mg, 0.1 mmol, 1.0 equiv).

[0186] (3) The residue was purified by silica gel rapid column chromatography with petroleum ether / ethyl acetate mixture as the eluent to obtain colorless oily alkenyl adipate (15.0 mg, yield 62%).

[0187] The R of the product was measured on a silica gel thin-layer plate using petroleum ether-ethyl acetate as the developing solvent (volume ratio of petroleum ether to ethyl acetate was 20:1). f = 0.3.

[0188] (4) The above-mentioned alkenylated adipate ester was placed into a 25 mL reaction tube, and Pd / C (1.5 mg, 10 mol%) and 1 mL MeOH were added to dissolve the mixture. Then hydrogen gas was introduced and the reaction was carried out at 35 °C for 4 h. After the reaction was completed, the mixture was directly filtered and evaporated to dryness to obtain the target product 1-methyl-6-pentyl 2-methyladipate (14.8 mg, yield 98%).

[0189] The structural characterization data of the product are as follows:

[0190] 1H NMR (400 MHz, CDCl3, 23 ºC, δ): 4.07 (t, J = 6.7 Hz, 2H), 3.68 (s,3H), 2.52 – 2.42 (m, 1H), 2.31 (t, J = 7.2 Hz, 2H), 1.76 – 1.57 (m, 5H), 1.52– 1.42 (m, 1H), 1.38 – 1.32 (m, 4H), 1.17 (d, J = 7.0 Hz, 3H), 0.92 (t, 3H)ppm.

[0191] 13 C NMR (100 MHz, CDCl3, 23 ºC, δ): 177.02, 173.57, 64.66, 51.67,39.33, 34.27, 33.26, 28.47, 28.22, 22.83, 22.44, 17.15, 14.07 ppm.

[0192] HRMS-ESI(m / z) calc'd for C 13 H 25 O4 [M+H] + 245.1747; found, 245.1740.

[0193] Example 14: Preparation of 1-methyl 6-((tetrahydrofuran-3-yl)methyl)-2-methyl adipic acid

[0194] The preparation process of 1-methyl 6-((tetrahydrofuran-3-yl)methyl)-2-methyl adipic acid is as follows:

[0195] Steps (1) and (2) are essentially the same as in Example 1. The difference is that benzyl acrylate is replaced with methyl acrylate (tetrahydrofuran-3-yl)acrylate (15.6 mg, 0.1 mmol, 1.0 equiv).

[0196] (3) The residue was purified by silica gel rapid column chromatography with petroleum ether / ethyl acetate mixture as the eluent to obtain colorless oily alkenyl adipate (17.2 mg, yield 67%).

[0197] The R of the product was measured on a silica gel thin-layer plate using petroleum ether-ethyl acetate as the developing solvent (volume ratio of petroleum ether to ethyl acetate was 20:1). f = 0.3.

[0198] (4) The above-mentioned alkenylated adipate ester was placed into a 25 mL reaction tube, and Pd / C (1.7 mg, 10 mol%) and 1 mL MeOH were added to dissolve the mixture. Then hydrogen gas was introduced and the reaction was carried out at 35 °C for 4 h. After the reaction was completed, the mixture was directly filtered and evaporated to dryness to obtain the target product 6-methoxy-5-methyl-6-oxohexanoic acid (15.6 mg, yield 90%).

[0199] The structural characterization data of the product are as follows:

[0200] 1 H NMR (400 MHz, CDCl3, 23 ºC, δ): 4.13 – 4.05 (m, 1H), 4.01 – 3.93(m, 1H), 3.88 – 3.81 (m, 2H), 3.78 – 3.71 (m, 1H), 3.67 (s, 3H), 3.61 – 3.52(m, 1H), 2.63 – 2.52 (m, 1H), 2.50 – 2.41 (m, 1H), 2.31 (t, J = 7.2 Hz, 2H), 2.09 – 1.98 (m, 1H), 1.74 – 1.57 (m, 4H), 1.49 – 1.40 (m, 1H), 1.16 (d, J =7.0 Hz, 3H) ppm.

[0201] 13 C NMR (100 MHz, CDCl3, 23 ºC, δ): 176.92, 173.34, 70.61, 67.79,65.90, 51.67, 39.25, 38.32, 34.08, 33.15, 29.02, 22.72, 17.14 ppm.

[0202] HRMS-ESI(m / z) calc'd for C 13 H 23 O5 [M+H] + 259.1540; found, 259.1534.

[0203] Example 15: Preparation of bis(6-chlorohexyl)2-methyl adipate

[0204] The preparation process of bis(6-chlorohexyl)2-methyl adipate is as follows:

[0205] Steps (1) and (2) are essentially the same as in Example 1. The difference is that benzyl acrylate is replaced with 6-chlorohexyl acrylate (19.0 mg, 0.1 mmol, 1.0 equiv) and methyl 2-methacrylate is replaced with 6-chlorohexyl methacrylate (102.0 mg, 0.5 mmol, 5.0 equiv).

[0206] (3) The residue was purified by silica gel rapid column chromatography with petroleum ether / ethyl acetate mixture as the eluent to obtain colorless oily alkenyl adipate (24.0 mg, yield 61%).

[0207] The R of the product was measured on a silica gel thin-layer plate using petroleum ether-ethyl acetate as the developing solvent (volume ratio of petroleum ether to ethyl acetate was 20:1). f = 0.3.

[0208] (4) The above-mentioned alkenylated adipate was placed in a 25 mL reaction tube, and Pd / C (2.4 mg, 10 mol%) and 1 mL MeOH were added to dissolve the mixture. Then hydrogen gas was introduced and the reaction was carried out at 35 °C for 4 h. After the reaction was completed, the mixture was directly filtered and evaporated to dryness to obtain the target product bis(6-chlorohexyl)2-methyl adipate (23.4 mg, yield 97%).

[0209] The structural characterization data of the product are as follows:

[0210] 1 H NMR (400 MHz, CDCl3, 23 ºC, δ): 4.07 (td, J = 6.7, 1.9 Hz, 4H), 3.54 (t, J = 6.7 Hz, 4H), 2.50 – 2.40 (m, 1H), 2.31 (t, J = 7.2 Hz, 2H), 1.83– 1.75 (m, 4H), 1.73 – 1.57 (m, 7H), 1.54 – 1.34 (m, 9H), 1.16 (d, J = 7.1Hz, 3H) ppm.

[0211] 13 C NMR (100 MHz, CDCl3, 23 ºC, δ): 176.57, 173.50, 64.34, 64.27, 45.03, 39.44, 34.21, 33.20, 32.55, 28.60, 28.59, 26.60, 25.38, 22.78, 17.21ppm.

[0212] HRMS-ESI(m / z) calc'd for C 19 H 35 Cl2O4 [M+H] + 397.1906; found, 397.1897.

[0213] Example 16: Preparation of dicyclohexyl 2-methyladipate

[0214] The preparation process of 2-methyladipic acid dicyclohexyl ester is as follows:

[0215] Steps (1) and (2) are essentially the same as in Example 1. The difference is that benzyl acrylate is replaced with cyclohexyl acrylate (15.4 mg, 0.1 mmol, 1.0 equiv), and methyl 2-methacrylate is replaced with cyclohexyl methacrylate (84.1 mg, 0.5 mmol, 5.0 equiv).

[0216] (3) The residue was purified by silica gel rapid column chromatography with petroleum ether / ethyl acetate mixture as the eluent to obtain colorless oily alkenyl adipate (18.0 mg, yield 56%).

[0217] The R of the product was measured on a silica gel thin-layer plate using petroleum ether-ethyl acetate as the developing solvent (volume ratio of petroleum ether to ethyl acetate was 20:1). f = 0.3.

[0218] (4) The above-mentioned alkenylated adipate ester was placed into a 25 mL reaction tube, and Pd / C (1.8 mg, 10 mol%) and 1 mL MeOH were added to dissolve the mixture. Then hydrogen gas was introduced and the reaction was carried out at 35 °C for 4 h. After the reaction was completed, the mixture was directly filtered and evaporated to dryness to obtain the target product 2-methyladipate dicyclohexyl ester (18.0 mg, yield 99%).

[0219] The structural characterization data of the product are as follows:

[0220] 1 H NMR (400 MHz, CDCl3, 23 ºC, δ): 4.81 – 4.72 (m, 2H), 2.47 – 2.36(m, 1H), 2.29 (t, J = 7.1 Hz, 2H), 1.88 – 1.79 (m, 4H), 1.77 – 1.50 (m, 10H),1.49 – 1.25 (m, 10H), 1.15 (d, J = 7.0 Hz, 3H) ppm.

[0221] 13C NMR (100 MHz, CDCl3, 23 ºC, δ): 176.02, 172.96, 72.57, 72.32,39.63, 34.69, 33.30, 31.78, 31.74, 31.69, 25.53, 23.87, 23.80, 22.93, 17.21ppm.

[0222] HRMS-ESI(m / z) calc'd for C 19 H 33 O4 [M+H] + 325.2373; found, 325.2365.

[0223] Example 17: Preparation of dioctyl 2-methylhexanoate

[0224] The preparation process of dioctyl 2-methyladipate is as follows:

[0225] Steps (1) and (2) are essentially the same as in Example 1. The difference is that benzyl acrylate is replaced with octyl acrylate (18.4 mg, 0.1 mmol, 1.0 equiv) and methyl 2-methacrylate is replaced with octyl 2-methacrylate (99.1 mg, 0.5 mmol, 5.0 equiv).

[0226] (3) The residue was purified by silica gel rapid column chromatography with petroleum ether / ethyl acetate mixture as the eluent to obtain colorless oily alkenyl adipate (26.8 mg, yield 70%).

[0227] The R of the product was measured on a silica gel thin-layer plate using petroleum ether-ethyl acetate as the developing solvent (volume ratio of petroleum ether to ethyl acetate was 20:1). f = 0.3.

[0228] (4) The above-mentioned alkenylated adipate ester was placed into a 25 mL reaction tube, and Pd / C (2.7 mg, 10 mol%) and 1 mL MeOH were added to dissolve the mixture. Then hydrogen gas was introduced and the reaction was carried out at 35 °C for 4 h. After the reaction was completed, the mixture was directly filtered and evaporated to dryness to obtain the target product, dioctyl 2-methyladipate (25.6 mg, yield 95%).

[0229] The structural characterization data of the product are as follows:

[0230] 1H NMR (400 MHz, CDCl3, 23 ºC, δ): 4 4.07 (dt, J = 6.8, 1.7 Hz, 4H), 2.50 – 2.40 (m, 1H), 2.31 (t, J = 7.2 Hz, 2H), 1.74 – 1.58 (m, 7H), 1.51 –1.41 (m, 1H), 1.39 – 1.24 (m, 20H), 1.17 (d, J = 7.0 Hz, 3H), 0.89 (t, J =6.7 Hz, 6H) ppm.

[0231] 13 C NMR (100 MHz, CDCl3, 23 ºC, δ): 176.64, 173.57, 64.66, 64.59,39.50, 34.30, 33.27, 31.92, 29.35, 29.34, 29.31, 28.79, 26.07, 26.06, 22.85,22.77, 17.21, 14.20ppm.

[0232] HRMS-ESI(m / z) calc'd for C 23 H 45 O4 [M+H] + 385.3312; found, 385.3302.

[0233] Example 18: Preparation of 2-methyladipic acid

[0234] The reaction formula for 2-methyladipic acid is as follows:

[0235]

[0236] The specific preparation process is as follows:

[0237] Steps (1) and (2) are essentially the same as in Example 1. The difference is that methyl methacrylate is replaced with 4-(trifluoromethyl)benzyl methacrylate (122.0 mg, 0.5 mmol, 5.0 equiv).

[0238] (3) The residue was purified by silica gel rapid column chromatography with petroleum ether / ethyl acetate mixture as the eluent to obtain colorless oily alkenyl adipate (32.5 mg, yield 80%).

[0239] The R of the product was measured on a silica gel thin-layer plate using petroleum ether-ethyl acetate as the developing solvent (volume ratio of petroleum ether to ethyl acetate was 20:1). f= 0.3.

[0240] (4) The above-mentioned alkenylated adipate ester was placed into a 25 mL reaction tube, and Pd / C (3.3 mg, 10 mol%) and 1 mL MeOH were added to dissolve the mixture. Then hydrogen gas was introduced and the reaction was carried out at 35 °C for 4 h. After the reaction was completed, the mixture was filtered directly and evaporated to dryness to obtain the target product 2-methyl adipic acid (12.0 mg, yield 94%).

[0241] The structural characterization data of the product are as follows:

[0242] 1 H NMR (400 MHz, CDCl3, 23 ºC, δ): 11.28 (s, 2H), 2.47 – 2.37 (m, 1H), 2.31 (t, J = 7.1 Hz, 2H), 1.72 – 1.58 (m, 3H), 1.49 – 1.39 (m, 1H), 1.13 (d,J = 7.0 Hz, 3H) ppm.

[0243] 13 C NMR (100 MHz, CDCl3, 23 ºC, δ): 182.99, 179.85, 39.31, 34.02, 32.86, 22.42, 16.98 ppm.

[0244] HRMS-ESI(m / z) calc'd for C7H 13 O4 [M+H] + 161.1808; found, 161.1805.

[0245] Example 19: Preparation of 2-methyladipic acid

[0246] The preparation process of 2-methyladipic acid is as follows:

[0247] Steps (1) and (2) are essentially the same as in Example 1. The difference is that methyl methacrylate is replaced with benzyl methacrylate (88.0 mg, 0.5 mmol, 5.0 equiv).

[0248] (3) The residue was purified by silica gel rapid column chromatography with petroleum ether / ethyl acetate mixture as the eluent to obtain colorless oily alkenyl adipate (25.4 mg, yield 75%).

[0249] The R of the product was measured on a silica gel thin-layer plate using petroleum ether-ethyl acetate as the developing solvent (volume ratio of petroleum ether to ethyl acetate was 20:1). f= 0.3.

[0250] (4) The above-mentioned alkenylated adipate ester was placed in a 25 mL reaction tube, and Pd / C (2.5 mg, 10 mol%) and 1 mL MeOH were added to dissolve the mixed reactants. Then hydrogen gas was introduced and the reaction was carried out at 35 °C for 4 h. After the reaction was completed, the product was directly filtered and evaporated to dryness to obtain a colorless oily product, which was then further purified. First, 5% NaOH solution was added to adjust the pH to 14, and the product was extracted three times with dichloromethane. The aqueous phase was retained, and the pH of the aqueous phase was adjusted to 1 with 1M HCl. Then the aqueous phase was directly evaporated to dryness using a vacuum pump to obtain a white solid. The product was then washed three times with dichloromethane and evaporated to dryness to obtain 2-methyladipic acid (11.4 mg, yield 95%).

[0251] The structural characterization data of the product are as follows:

[0252] 1 H NMR (400 MHz, CDCl3, 23 ºC, δ): 2.46 – 2.39 (m, 1H), 2.31 (t, J =7.0 Hz, 2H), 1.72 – 1.57 (m, 3H), 1.50 – 1.39 (m, 1H), 1.13 (d, J = 7.0 Hz,3H) ppm.

[0253] 13 C NMR (100 MHz, CDCl3, 23 ºC, δ): 183.00, 179.85, 39.32, 34.02, 32.87, 22.42, 16.98 ppm.

[0254] HRMS-ESI(m / z) calc'd for C7H 13 O4 [M+H] + 161.1808; found, 161.1804.

[0255] Example 20: Preparation of 2-Ethylhexanoic acid

[0256] The preparation process of 2-ethylhexanoic acid is as follows:

[0257] Steps (1) and (2) are essentially the same as in Example 1. The difference is that methyl methacrylate is replaced with benzyl 2-ethylacrylate (99.5 mg, 0.5 mmol, 5.0 equiv).

[0258] (3) The residue was purified by silica gel rapid column chromatography with petroleum ether / ethyl acetate mixture as the eluent to obtain colorless oily alkenyl adipate (22.2 mg, yield 63%).

[0259] The R of the product was measured on a silica gel thin-layer plate using petroleum ether-ethyl acetate as the developing solvent (volume ratio of petroleum ether to ethyl acetate was 20:1). f = 0.3.

[0260] (4) The above-mentioned alkenylated adipate ester was placed in a 25 mL reaction tube, and Pd / C (2.2 mg, 10 mol%) and 1 mL MeOH were added to dissolve the mixed reactants. Then hydrogen gas was introduced and the reaction was carried out at 35 °C for 4 h. After the reaction was completed, the product was directly filtered and evaporated to dryness to obtain a colorless oily product, which was then further purified. First, 5% NaOH solution was added to adjust the pH to 14, and the product was extracted three times with dichloromethane. The aqueous phase was retained, and the pH of the aqueous phase was adjusted to 1 with 1M HCl. Then the aqueous phase was directly evaporated to dryness using a vacuum pump to obtain a white solid. The product was then washed three times with dichloromethane and evaporated to dryness to obtain 2-ethylhexanoic acid (10.2 mg, yield 93%).

[0261] The structural characterization data of the product are as follows:

[0262] 1 H NMR (400 MHz, CDCl3, 23 ºC, δ): 9.12 (s, 2H), 2.47 – 2.29 (m, 3H), 1.77 – 1.63 (m, 4H), 1.62 – 1.50 (m, 2H), 0.96 (t, J = 7.4 Hz, 3H) ppm.

[0263] 13 C NMR (100 MHz, CDCl3, 23 ºC, δ): 182.35, 179.69, 46.95, 34.09, 31.11, 25.27, 22.65, 11.78 ppm.

[0264] HRMS-ESI(m / z) calc'd for C8H 15 O4 [M+H] + 175.0965; found, 175.0962.

[0265] Example 21: Preparation of 2-Butyladipic Acid

[0266] The preparation process of 2-butyladipic acid is as follows:

[0267] Steps (1) and (2) are essentially the same as in Example 1. The difference is that methyl methacrylate is replaced with benzyl 2-butylacrylate (109.1 mg, 0.5 mmol, 5.0 equiv).

[0268] (3) The residue was purified by silica gel rapid column chromatography with petroleum ether / ethyl acetate mixture as the eluent to obtain colorless oily alkenyl adipate (24.7 mg, yield 65%).

[0269] The R of the product was measured on a silica gel thin-layer plate using petroleum ether-ethyl acetate as the developing solvent (volume ratio of petroleum ether to ethyl acetate was 20:1). f = 0.3.

[0270] (4) The above-mentioned alkenyl adipate ester was placed in a 25 mL reaction tube, and Pd / C (2.5 mg, 10 mol%) and 1 mL MeOH were added to dissolve the mixed reactants. Then hydrogen gas was introduced and the reaction was carried out at 35 °C for 4 h. After the reaction was completed, the product was directly filtered and evaporated to dryness to obtain a colorless oily product, which was then further purified. First, 5% NaOH solution was added to adjust the pH to 14, and the product was extracted three times with dichloromethane. The aqueous phase was retained, and the pH of the aqueous phase was adjusted to 1 with 1M HCl. Then the aqueous phase was directly evaporated to dryness using a vacuum pump to obtain a white solid. The product was then washed three times with dichloromethane and evaporated to dryness to obtain 2-butyladipic acid (11.2 mg, yield 85%).

[0271] The structural characterization data of the product are as follows:

[0272] 1 H NMR (400 MHz, CDCl3, 23 ºC, δ): 8.90 (s, 2H), 2.49 – 2.22 (m, 3H), 1.70 (h, J = 6.3 Hz, 4H), 1.61 – 1.45 (m, 2H), 1.39 – 1.26 (m, 4H), 0.91 (t,J = 6.8 Hz, 3H) ppm.

[0273] 13 C NMR (100 MHz, CDCl3, 23 ºC, δ): 182.48, 179.63, 45.46, 34.13, 31.98, 31.59, 29.58, 22.72, 14.02 ppm.

[0274] HRMS-ESI(m / z) calc'd for C 10 H 19 O4 [M+H] +203.1278; found, 203.1275.

[0275] Example 22: Preparation of 2-propyl adipic acid

[0276] The preparation process of 2-propyl adipic acid is as follows:

[0277] Steps (1) and (2) are essentially the same as in Example 1. The difference is that methyl methacrylate is replaced with benzyl 2-propylacrylate (102.1 mg, 0.5 mmol, 5.0 equiv).

[0278] (3) The residue was purified by silica gel rapid column chromatography with petroleum ether / ethyl acetate mixture as the eluent to obtain colorless oily alkenyl adipate (24.5 mg, yield 67%).

[0279] The R of the product was measured on a silica gel thin-layer plate using petroleum ether-ethyl acetate as the developing solvent (volume ratio of petroleum ether to ethyl acetate was 20:1). f = 0.3.

[0280] (4) The above-mentioned alkenyl adipate was placed in a 25 mL reaction tube, and Pd / C (2.5 mg, 10 mol%) and 1 mL MeOH were added to dissolve the mixed reactants. Then hydrogen gas was introduced and the reaction was carried out at 35 °C for 4 h. After the reaction was completed, the product was directly filtered and evaporated to dryness to obtain a colorless oily product, which was then further purified. First, 5% NaOH solution was added to adjust the pH to 14, and the product was extracted three times with dichloromethane. The aqueous phase was retained, and the pH of the aqueous phase was adjusted to 1 with 1M HCl. Then the aqueous phase was directly evaporated to dryness using a vacuum pump to obtain a white solid. The product was then washed three times with dichloromethane and evaporated to dryness to obtain 2-propyl adipate (11.5 mg, yield 91%).

[0281] The structural characterization data of the product are as follows:

[0282] 1 H NMR (400 MHz, CDCl3, 23 ºC, δ): 8.23 ​​(s, 2H), 2.51 – 2.29 (m, 3H), 1.77 – 1.63 (m, 4H), 1.59 – 1.28 (m, 4H), 0.93 (t, J = 7.2 Hz, 3H) ppm.

[0283] 13C NMR (100 MHz, CDCl3, 23 ºC, δ): 182.58, 179.74, 45.22, 34.39, 34.09, 31.55, 22.66, 20.61, 14.07 ppm.

[0284] HRMS-ESI(m / z) calc'd for C9H 17 O4 [M+H] + 189.1121; found, 189.1118.

[0285] Example 23: Preparation of 2-isopropyl adipic acid

[0286] The preparation process of 2-isopropyl adipic acid is as follows:

[0287] Steps (1) and (2) are essentially the same as in Example 1. The difference is that methyl methacrylate is replaced with benzyl 2-isopropylacrylate (102.1 mg, 0.5 mmol, 5.0 equiv).

[0288] (3) The residue was purified by silica gel rapid column chromatography with petroleum ether / ethyl acetate mixture as the eluent to obtain colorless oily alkenyl adipate (22.0 mg, yield 60%).

[0289] The R of the product was measured on a silica gel thin-layer plate using petroleum ether-ethyl acetate as the developing solvent (volume ratio of petroleum ether to ethyl acetate was 20:1). f = 0.3.

[0290] (4) The above-mentioned alkenylated adipate ester was placed in a 25 mL reaction tube, and Pd / C (2.2 mg, 10 mol%) and 1 mL MeOH were added to dissolve the mixed reactants. Then hydrogen gas was introduced and the reaction was carried out at 35 °C for 4 h. After the reaction was completed, the product was directly filtered and evaporated to dryness to obtain a colorless oily product, which was then further purified. First, 5% NaOH solution was added to adjust the pH to 14, and the product was extracted three times with dichloromethane. The aqueous phase was retained, and the pH of the aqueous phase was adjusted to 1 with 1M HCl. Then the aqueous phase was directly evaporated to dryness using a vacuum pump to obtain a white solid. The product was then washed three times with dichloromethane and evaporated to dryness to obtain 2-isopropyladipic acid (9.8 mg, yield 87%).

[0291] The structural characterization data of the product are as follows:

[0292] 1H NMR (400 MHz, CDCl3, 23 ºC, δ): 2.48 – 2.32 (m, 2H), 2.21 – 2.11(m, 1H), 1.97 – 1.87 (m, 1H), 1.78 – 1.53 (m, 4H), 0.98 (dd, J = 6.8, 2.6 Hz, 6H) ppm.

[0293] 13 C NMR (100 MHz, CDCl3, 23 ºC, δ): 181.90, 179.70, 52.44, 34.14, 30.52, 28.80, 23.08, 20.56, 20.13 ppm.

[0294] HRMS-ESI(m / z) calc'd for C9H 17 O4 [M+H] + 189.1121; found, 189.1117.

[0295] Example 24: Preparation of methyl 5-cyano-2-methylpentanoate

[0296] The preparation process of methyl 5-cyano-2-methylpentanoate is as follows:

[0297] Steps (1) and (2) are essentially the same as in Example 1. The difference is that benzyl acrylate is replaced with acrylonitrile (10.6 mg, 0.2 mmol, 1.0 equiv), and the amount of methyl 2-methacrylate is (100.1 mg, 1.0 mmol, 5.0 equiv).

[0298] (3) The residue was purified by silica gel rapid column chromatography with petroleum ether / ethyl acetate mixture as the eluent to obtain a colorless oily product (19.3 mg, yield 63%).

[0299] The R of the product was measured on a silica gel thin-layer plate using petroleum ether-ethyl acetate as the developing solvent (volume ratio of petroleum ether to ethyl acetate was 5:1). f = 0.3.

[0300] (4) The above-mentioned alkenylated adipate ester was placed in a 25 mL reaction tube, and Pd / C (1.9 mg, 10 mol%) and 1 mL MeOH were added to dissolve the mixed reactants. Then hydrogen gas was introduced and the reaction was carried out at 35 °C for 4 h. After the reaction was completed, the product was directly filtered and evaporated to dryness to obtain a colorless oily product, which was then further purified. First, 5% NaOH solution was added to adjust the pH to 14, and the product was extracted three times with dichloromethane. The aqueous phase was retained, and the pH of the aqueous phase was adjusted to 1 with 1M HCl. Then the aqueous phase was directly evaporated to dryness by vacuum pump to obtain a white solid. The product was washed three times with dichloromethane and evaporated to dryness to obtain methyl 5-cyano-2-methylpentanoate (11.6 mg, yield 60%).

[0301] The structural characterization data of the product are as follows:

[0302] 1 H NMR (400 MHz, CDCl3, 23 ºC, δ): 3.62 (s, 3H), 2.47 – 2.37 (m, 1H), 2.29 (t, J = 7.2 Hz, 2H), 1.78 – 1.68 (m, 1H), 1.64 – 1.57 (m, 2H), 1.57 –1.49 (m, 1H), 1.12 (d, J = 7.0 Hz, 3H) ppm.

[0303] 13 C NMR (100 MHz, CDCl3, 23 ºC, δ): 176.42, 119.46, 51.85, 38.88, 32.65, 23.31, 17.24 ppm.

[0304] HRMS-ESI(m / z) calc'd for C8H 14 NO2 [M+H] + 156.1019; found, 156.1016.

[0305] Example 25: Gram-scale preparation of 2-methyladipic acid

[0306] The specific operation is the same as in Example 19. The specific preparation process is as follows:

[0307] (1) In an argon atmosphere, cobalt catalyst (444 mg, 10 mol%), zinc powder (1.3 g, 0.2 mmol, 2.0 equiv), benzyl acrylate (1.62 g, 10 mmol, 1.0 equiv), and 2-methyl acrylate (8.8 g, 50 mmol, 5.0 equiv) were added to the reaction flask.

[0308] Then add 0.5 mL of chlorobenzene to dissolve and mix the reactants, and finally add BTMG (1.37 g, 80 mol%).

[0309] (2) The reaction mixture was placed under 455 nm LEDs and stirred at room temperature for 24 hours. The mixture was washed with ethyl acetate and transferred to a flask. The volatiles were removed under vacuum to obtain the residue.

[0310] (3) The residue was purified by silica gel rapid column chromatography with petroleum ether / ethyl acetate mixture as the eluent to obtain colorless oily alkenyl adipate (2.54 g, yield 75%).

[0311] The R of the product was measured on a silica gel thin-layer plate using petroleum ether-ethyl acetate as the developing solvent (volume ratio of petroleum ether to ethyl acetate was 20:1). f = 0.3.

[0312] (4) The above-mentioned alkenylated adipate ester was placed in a 25 mL reaction tube, and Pd / C (250 mg, 10 mol%) and 1 mL MeOH were added to dissolve the mixed reactants. Then hydrogen gas was introduced and the reaction was carried out at 35 °C for 4 h. After the reaction was completed, the product was directly filtered and evaporated to dryness to obtain a colorless oily product, which was then further purified. First, 5% NaOH solution was added to adjust the pH to 14, and the product was extracted three times with dichloromethane. The aqueous phase was retained, and the pH of the aqueous phase was adjusted to 1 with 1M HCl. Then the aqueous phase was directly evaporated to dryness by vacuum pump to obtain a white solid. The product was then washed three times with dichloromethane and evaporated to dryness to obtain 2-methyladipic acid (1.14 g, yield 95%).

[0313] The above detailed embodiments describe the implementation of the present invention; however, the present invention is not limited to the specific details described in the above embodiments. Within the scope of the claims and technical concept of the present invention, various simple modifications and changes can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

Claims

1. A method for preparing adipic acid derivatives from acrylates with similar polarity using cobalt catalysis, characterized in that, Includes the following steps: Under an inert atmosphere, acrylate of formula I, 2-alkyl acrylate of formula II, cobalt catalyst, base, and reducing agent are mixed in an organic solvent, and the mixture is irradiated with light of wavelength 365 nm-455 nm to prepare alkenylated adipate of formula III, as shown in the following reaction formula: ； The alkenyl adipate of formula III and Pd / C are mixed in methanol, and hydrogen is introduced to carry out a hydrogenation reaction to obtain the adipic acid derivative of formula IV, as shown in the following reaction formula: ； Among them, group R 1 R 2 and R 3 Each group is independently selected from one of the following: hydrogen, aliphatic chain, benzyl, aromatic group, and aromatic heterocyclic group.

2. The method for preparing adipic acid derivatives from cobalt-catalyzed acrylates with similar polarity according to claim 1, characterized in that, The chemical structure of the cobalt catalyst is as follows: ； Among them, group R 4 It is one of halogens and alkyl groups; L is one of pyridines, imidazoles, anilines, phenethylamines, butylamines, and isobutylamines. Furthermore, the chemical structure of the cobalt catalyst is as follows: 。 3. The method for preparing adipic acid derivatives from cobalt-catalyzed acrylates with similar polarity according to claim 1, characterized in that, The reducing agent is at least one of zinc powder, aluminum powder, manganese powder, and magnesium powder; Furthermore, the reducing agent is zinc powder.

4. The method for preparing adipic acid derivatives from cobalt-catalyzed acrylates with similar polarity according to claim 1, characterized in that, The base is at least one selected from 2-tert-butyl-1,1,3,3-tetramethylguanidine, tetramethylguanidine, and triethylamine; Further, the base is 2-tert-butyl-1,1,3,3-tetramethylguanidine.

5. The method for preparing adipic acid derivatives from cobalt-catalyzed acrylates with similar polarity according to claim 1, characterized in that, The aliphatic chain group is one of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, hexyl, heptyl, octyl, and dodecyl; the aromatic group is one of phenyl, naphthyl, and fused-ring aryl; the aromatic heterocyclic group is selected from furanyl, pyridinyl, thiophene, pyrroleyl, benzoxazolyl, benzofuranyl, isoquinolinyl, and quinolinyl.

6. The method for preparing adipic acid derivatives from cobalt-catalyzed acrylates with similar polarity according to claim 1, characterized in that, The acrylate represented by Formula I is any one of the following chemical structural formulas: ； Among them, group R 5 For Me, OMe, t One of Bu, F, Cl, Br, I, and CF3.

7. The method for preparing adipic acid derivatives from cobalt-catalyzed acrylates with similar polarity according to claim 6, characterized in that, The 2-alkyl acrylate represented by Formula II is any one of the following chemical structural formulas: ； Group R 5 For Me, OMe, t One of Bu, F, Cl, Br, I, CF3, R 6 It can be Ph or Bn.

8. The method for preparing adipic acid derivatives from cobalt-catalyzed acrylates with similar polarity according to claim 1, characterized in that, When preparing the adipic acid derivative, the molar ratio of the reducing agent to the acrylate shown in Formula I is (1-3):

1.

9. As described in claim 1, characterized in that, When preparing the adipic acid derivative, the molar ratio of the base to the acrylate represented by Formula I is (0.4-1):

1.

10. The method for preparing adipic acid derivatives from cobalt-catalyzed acrylates with similar polarity according to claim 1, characterized in that, The molar ratio of the acrylate shown in Formula I to the 2-alkyl acrylate shown in Formula II is 1:(2-5).

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