Preparation method of alpha-acyloxy ketone compound

Abstract

The invention discloses a preparation method of an alpha-acyloxy ketone compound, which comprises the following step: under the action of an imidazole catalyst, carrying out reaction on a hydroxy ketone compound and acid anhydride to prepare the alpha-acyloxy ketone compound. According to the preparation method disclosed by the invention, the alpha-acyloxy ketone compound is selectively synthesized by taking the alpha-hydroxy ketone compound and the anhydride as raw materials, the anhydride can be used as a substrate and a reaction solvent under the action of an imidazole catalyst, and the synthesis method is a'one-pot method 'preparation method; the method has the advantages of simplicity, feasibility, no metal participation, no need of adding any oxidizing agent or reducing agent, wide substrate application range, high atom utilization rate, high yield and the like, the yield of part of alpha-acyloxy ketone compound products is up to 90%, pyridine and other reagents with pungent smell in the traditional esterification reaction are avoided, and the method is suitable for industrial production. The requirements of green synthetic chemistry development are met, and industrial production is facilitated.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and specifically relates to a method for preparing an alpha-acyloxy ketone compound. Background Art

[0002] α-Acyloxy ketone is an organic molecule with adjacent carbonyl and acyloxy groups. Its structure is widely present in many natural products and bioactive molecules. It is also the core structure of some drug molecules (such as paclitaxel, cortisone acetate, etc.). Drug molecules containing this structure usually show good anti-cancer, anti-inflammatory, antibacterial and other activities. At the same time, because α-acyloxy ketone contains multiple functional sites, it can also be widely used as a synthon in the field of organic synthesis, such as cyclization reaction, deoxygenation reaction of ester group, favorskii rearrangement, etc. Therefore, the synthesis of α-acyloxy ketone has received extensive attention from scientific researchers.

[0003] The main method for the traditional synthesis of α-acyloxy ketones is the oxidative coupling reaction of ketones with metal catalysts, such as Mn(OAc)3, Pb(OAc)4. However, these methods inevitably have some disadvantages, such as excessive by-products, poor selectivity, and the use of toxic metal oxidants. In recent years, with the rise and continuous development of green synthetic chemistry, exploring efficient preparation methods of α-acyloxy ketones that meet the requirements of green chemistry and sustainable chemistry has become a research focus, such as using low-toxic, cheap and easily available iodine reagents as catalysts, or adopting green and efficient photochemical methods to synthesize α-acyloxy ketones. Although various new methods are constantly being reported, these methods have problems such as complex reaction systems and difficult to obtain raw materials. Therefore, it is still necessary to explore a green synthesis method for α-acyloxy ketones with economical and readily available raw materials, simple operation, and excellent yield. Summary of the invention

[0004] In order to overcome the problems existing in the prior art, the object of the present invention is to provide a method for preparing an α-acyloxy ketone compound.

[0005] In order to achieve the above object, the technical solution adopted by the present invention is:

[0006] The present invention provides a method for preparing an α-acyloxy ketone compound, comprising the following steps: reacting a hydroxy ketone compound as shown in formula (I) with an acid anhydride as shown in formula (II) under the action of an imidazole catalyst to obtain an α-acyloxy ketone compound as shown in formula (III), wherein the reaction formula is as follows:

[0007]

[0008] Among them, R 1 is selected from aryl or aralkyl; R 2 is selected from aryl, aralkyl or alkyl; R3 It is an alkyl group.

[0009] Preferably, the R 1 or R 2 The aryl groups are independently substituted or unsubstituted mononuclear aryl groups; when R 1 or R 2 When the aryl group is a substituted mononuclear aryl group, the substituent is a C1-C7 alkyl group, a C1-C7 alkoxy group, a halogen group, a cyano group, an acetyl group, a nitro group, an alkoxycarbonyl group or an ester group.

[0010] In general, the term "substituted" means that at least one hydrogen present on a group (e.g., a carbon or nitrogen atom) is replaced with a permissible substituent, e.g., a substituent that, when substituted, produces a stable compound, e.g., a compound that does not spontaneously undergo transformation (e.g., by rearrangement, cyclization, elimination, or other reaction). Unless otherwise specified, a "substituted" group has substituents at one or more substitutable positions of the group, and when more than one position in any given structure is substituted, the substituent at each position is the same or different.

[0011] More preferably, the R 1 is selected from the group consisting of phenyl, 4-methylphenyl, 4-ethylphenyl, 4-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 3-fluorophenyl, 3-chlorophenyl, 3-methoxyphenyl, and 2-thienyl; wherein R 2 is selected from the group consisting of phenyl, 4-methylphenyl, 4-ethylphenyl, 4-methoxyphenyl, methyl, ethyl, and n-propyl; 3 Selected from methyl, ethyl, n-propyl, isopropyl, tert-butyl, chloroethyl.

[0012] Further preferably, the α-acyloxy ketone compound is selected from one of Formula 3a to Formula 3t:

[0013]

[0014]

[0015] Preferably, the imidazole catalyst is selected from at least one of 2-methylimidazole, 2-ethylimidazole, 2-ethyl-4-methylimidazole and 2-phenylimidazole.

[0016] Preferably, the reaction time of the reaction is 9 to 13 hours.

[0017] More preferably, the reaction time of the reaction is 9 to 11 hours.

[0018] Preferably, the reaction temperature of the reaction is 100-150°C.

[0019] More preferably, the reaction temperature of the reaction is 110-130°C.

[0020] Preferably, the molar ratio of the hydroxyketone compound to the imidazole catalyst is 1:(1-4).

[0021] More preferably, the molar ratio of the hydroxyketone compound to the imidazole catalyst is 1:(1.5-2.5).

[0022] Preferably, the usage ratio of the hydroxyketone compound to the acid anhydride is 1 mmol: (7-15) mL.

[0023] More preferably, the usage ratio of the hydroxyketone compound to the acid anhydride is 1 mmol: (8-12) mL.

[0024] Preferably, the method comprises the following steps: reacting a hydroxyketone compound as shown in formula (I) and an acid anhydride as shown in formula (II) under the action of an imidazole catalyst to obtain a product mixture, removing the acid anhydride, and purifying to obtain an α-acyloxy ketone compound as shown in formula (III); the purification comprises extracting the product mixture, washing the organic phase, drying and separating by column chromatography in sequence.

[0025] More preferably, the method for removing the anhydride is distillation under reduced pressure.

[0026] More preferably, the extraction uses dichloromethane as the extractant.

[0027] More preferably, the washing is performed with saturated saline solution.

[0028] More preferably, the drying is carried out using anhydrous sodium sulfate.

[0029] More preferably, the column chromatography separation uses a silica gel chromatography column.

[0030] The beneficial effects of the present invention are:

[0031] The invention provides a method for preparing an alpha-acyloxy ketone compound. The alpha-acyloxy ketone compound is selectively synthesized by taking an alpha-hydroxy ketone compound and an acid anhydride as raw materials. Under the action of an imidazole catalyst, the acid anhydride can be used as both a substrate and a reaction solvent. The synthesis method is a "one-pot method" and has the advantages of being simple and easy to operate, free of metal involvement, no need to add any oxidant or reductant, a wide range of substrate applications, high atomic utilization, high yield, etc. The yield of some alpha-acyloxy ketone compound products is as high as 90%, and the use of reagents with irritating odors such as pyridine in traditional esterification reactions is avoided, which meets the requirements of the development of green synthetic chemistry and is conducive to industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1This is the X-ray single crystal diffraction pattern of α-acyloxy ketone compound 3q. DETAILED DESCRIPTION

[0033] The present invention is further described in detail below through specific examples. The raw materials used in the following examples, unless otherwise specified, can be obtained from conventional commercial sources or prepared and separated by simple synthesis; the processes used, unless otherwise specified, are conventional processes in the art.

[0034] Example 1

[0035] This embodiment provides a method for preparing an α-acyloxy ketone compound 3a, wherein the structural formula of the α-acyloxy ketone compound 3a is Its CAS number is 574-06-1, and its synthesis steps are as follows:

[0036] 0.30mmol (0.0804g) of benzoin and 0.60mmol (0.0492g) of 2-methylimidazole were added to 3mL of acetic anhydride, and the mixture was stirred under reflux at 120°C for 10 hours. After the reaction was completed, the remaining acetic anhydride was removed by distillation under reduced pressure. The reactants were completely transferred to a separatory funnel, extracted three times with dichloromethane (15mL), washed with saturated brine, the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by a rotary evaporator. The crude product was purified and separated by silica gel column chromatography to obtain α-acyloxy ketone compound 3a (white solid, mp: 71-73°C, 71.6mg, yield 94%).

[0037] The NMR information of the product is: 1 H NMR (600MHz, CDCl3), δ, ppm: 2.19 (s, 3H, CH3), 6.87 (s, 1H, CH), 7.33-7.39 (m, 5H, ArH ),7.46(d,J=7.8Hz,2H,ArH),7.49(t,J=7.2Hz,1H,ArH),7.93(d,J=7.2Hz,2H,ArH); 13 C NMR (150 MHz, CDCl3), δ, ppm: 20.9, 77.8, 128.7, 128.8, 128.9, 129.2, 129.4, 133.7, 170.5, 193.8. The above results show that the structure of the product is consistent with the expected one.

[0038] Example 2

[0039] This example provides a method for preparing an α-acyloxy ketone compound 3b, wherein the structural formula of the α-acyloxy ketone compound 3b is Its CAS number is 119267-75-3, and its synthesis steps are as follows:

[0040] 0.30mmol 4,4'-dimethylbenzoin and 0.60mmol (0.0492g) 2-methylimidazole were added to 3mL acetic anhydride, and the mixture was stirred under reflux at 120°C for 10 hours. After the reaction was completed, the remaining acetic anhydride was removed by distillation under reduced pressure. The reactants were completely transferred to a separatory funnel, extracted three times with dichloromethane (15mL), washed with saturated brine, the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The crude product was purified and separated by silica gel column chromatography to obtain α-acyloxy ketone compound 3b (colorless oily liquid, 77mg, yield 91%).

[0041] The NMR information of the product is: 1 H NMR (600MHz, CDCl3), δ, ppm: 2.20 (s, 3H, CH3), 2.31 (s, 3H, CH3), 2.35 (s, 3H, CH3), 6.83 (s, 1H, CH), 7.17 (d,J=7.8Hz,2H,ArH),7.19(d,J=8.4Hz,2H,ArH),7.35(d,J=7.8Hz,2H,ArH),7.84(d,J=8.4Hz,2H,ArH); 13 C NMR (150 MHz, CDCl3), δ, ppm: 21.0, 21.3, 21.8, 77.6, 128.8, 129.0, 129.4, 129.9, 131.0, 132.2, 139.4, 144.5, 170.6, 193.4. The above results show that the structure of the product is consistent with the expectation.

[0042] Example 3

[0043] This example provides a method for preparing an α-acyloxy ketone compound 3c, wherein the structural formula of the α-acyloxy ketone compound 3c is The synthesis steps are as follows:

[0044] 0.30mmol 1,2-bis(4-ethylphenyl)-2-hydroxyethanone and 0.60mmol (0.0492g) 2-methylimidazole were added to 3mL acetic anhydride, and the mixture was stirred under reflux at 120°C for 10 hours. After the reaction was completed, the remaining acetic anhydride was removed by vacuum distillation. The reactants were completely transferred to a separatory funnel, extracted three times with dichloromethane (15mL), washed with saturated brine, the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The crude product was purified and separated by silica gel column chromatography to obtain α-acyloxy ketone compound 3c (colorless oily liquid, 85.6mg, yield 92%).

[0045] The NMR and mass spectrometry information of the product are:

[0046] 1 H NMR (600MHz, CDCl3), δ, ppm: 1.20 (t, J=7.8Hz, 3H, CH3-1), 1.21 (t, J=7.2Hz, 3H, C H3-20),2.20(s,3H,CH3-11),2.62(q,J=7.8Hz,2H,CH3-2),2.66(q,J=7.2Hz,2H, CH3-19),6.84(s,1H,CH-9),7.20(d,J=7.8Hz,2H,ArH-4,5),7.22(d,J=8.4Hz,2H ,ArH-16,17),7.39(d,J=7.8Hz,2H,ArH-6,7),7.88(d,J=8.4Hz,2H,ArH-14,15);

[0047] 13 C NMR (150MHz, CDCl3), δ, ppm: 15.1, 15.4, 21.0, 28.7, 29.1, 77.6, 128.3, 128.8, 128.9, 129.2, 131.2, 132.4, 145.7, 150.6, 170.6, 193.4;

[0048] ESI-HRMS, m / z: Calcd for C 20 H 21 O3[MH] - :309.1496,Found:309.1492.

[0049] The results of hydrogen nuclear magnetic resonance spectrum, carbon nuclear magnetic resonance spectrum and high-resolution mass spectrometry showed that the structure of compound 1 was consistent with expectations.

[0050] Example 4

[0051] This embodiment provides a method for preparing an α-acyloxy ketone compound 3d, wherein the structural formula of the α-acyloxy ketone compound 3d is Its CAS number is 1678-44-0, and its synthesis steps are as follows:

[0052] 0.30mmol of p-anisyl and 0.60mmol (0.0492g) of 2-methylimidazole were added to 3mL of acetic anhydride, and the mixture was stirred under reflux at 120°C for 10 hours. After the reaction was completed, the remaining acetic anhydride was removed by distillation under reduced pressure. The reactants were completely transferred to a separatory funnel, extracted three times with dichloromethane (15mL), washed with saturated brine, the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by a rotary evaporator. The crude product was purified and separated by silica gel column chromatography to obtain α-acyloxy ketone compound 3d (colorless oily liquid, 91.2mg, yield 82%).

[0053] The NMR information of the product is: 1 H NMR(600MHz,CDCl3),δ,ppm:2.18(s,3H,CH3),3.76(s,3H,OCH3),3.80(s,3H,OCH3),6.80(s,1H,CH),6.8 3(d,J=9.0Hz,2H,ArH),6.88(d,J=9.0Hz,2H,ArH),7.38(d,J=9.0Hz,2H,ArH),7.92(d,J=9.0Hz,2H,ArH); 13 C NMR (150 MHz, CDCl3), δ, ppm: 21.0, 55.4, 55.5, 77.1, 113.9, 114.6, 126.2, 127.6, 130.3, 131.2, 160.4, 163.8, 170.7, 192.2. The above results show that the structure of the product is consistent with the expected.

[0054] Example 5

[0055] This embodiment provides a method for preparing an α-acyloxy ketone compound 3e, wherein the structural formula of the α-acyloxy ketone compound 3e is Its CAS number is 69673-81-0, and its synthesis steps are as follows:

[0056] 0.30mmol 2-hydroxy-1-(4-methylphenyl)propan-1-one and 0.60mmol (0.0492g) 2-methylimidazole were added to 3mL acetic anhydride, and the mixture was stirred under reflux at 120°C for 10 hours. After the reaction was completed, the remaining acetic anhydride was removed by distillation under reduced pressure. The reactants were completely transferred to a separatory funnel, extracted three times with dichloromethane (15mL), washed with saturated brine, the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by a rotary evaporator. The crude product was purified and separated by silica gel column chromatography to obtain α-acyloxy ketone compound 3e (colorless oily liquid, 51.3mg, yield 83%).

[0057] The NMR information of the product is: 1 H NMR (600MHz, CDCl3), δ, ppm: 1.50 (d, J = 7.2Hz, 3H, CH3), 2.12 (s, 3H, CH3), 2.39 (s, 3H, CH3),5.94(q,J=7.2Hz,1H,CH),7.25(d,J=7.8Hz,2H,ArH),7.83(d,J=7.8Hz,2H,ArH); 13C NMR (150 MHz, CDCl3), δ, ppm: 17.3, 20.8, 21.8, 71.4, 128.6, 129.5, 131.9, 144.6, 170.4, 196.4. The above results show that the structure of the product is consistent with the expectation.

[0058] Example 6

[0059] This embodiment provides a method for preparing an α-acyloxy ketone compound 3f, wherein the structural formula of the α-acyloxy ketone compound 3f is Its CAS number is 200353-84-0, and its synthesis steps are as follows:

[0060] 0.30mmol 2-hydroxy-1-(4-methoxyphenyl)propan-1-one and 0.60mmol (0.0492g) 2-methylimidazole were added to 3mL acetic anhydride, and the mixture was stirred under reflux at 120°C for 10 hours. After the reaction was completed, the remaining acetic anhydride was removed by distillation under reduced pressure. The reactants were completely transferred to a separatory funnel, extracted three times with dichloromethane (15mL), washed with saturated brine, the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by a rotary evaporator. The crude product was purified and separated by silica gel column chromatography to obtain α-acyloxy ketone compound 3f (colorless oily liquid, 56.6mg, yield 85%).

[0061] The NMR information of the product is: 1 H NMR (600MHz, CDCl3), δ, ppm: 1.52 (d, J = 7.2Hz, 3H, CH3), 2.14 (s, 3H, CH3), 3.86 (s, 3H, CH3),5.94(q,J=7.2Hz,1H,CH),6.95(d,J=9.0Hz,2H,ArH),7.93(d,J=9.0Hz,2H,ArH); 13 C NMR (150 MHz, CDCl3), δ, ppm: 17.4, 20.8, 55.5, 71.2, 114.0, 127.2, 130.8, 163.9, 170.4, 195.3. The above results show that the structure of the product is consistent with the expectation.

[0062] Example 7

[0063] This embodiment provides a method for preparing an α-acyloxy ketone compound 3g, wherein the structural formula of the α-acyloxy ketone compound 3g is Its CAS number is 2411629-40-6, and its synthesis steps are as follows:

[0064] 0.30mmol 2-hydroxy-1-(4-fluorophenyl)propan-1-one and 0.60mmol (0.0492g) 2-methylimidazole were added to 3mL acetic anhydride, and the mixture was stirred under reflux at 120°C for 10 hours. After the reaction was completed, the remaining acetic anhydride was removed by vacuum distillation. The reactants were completely transferred to a separatory funnel, extracted three times with dichloromethane (15mL), washed with saturated brine, the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by a rotary evaporator. The crude product was purified and separated by silica gel column chromatography to obtain 3g of α-acyloxy ketone compound (colorless oily liquid, 46.0mg, yield 73%).

[0065] The NMR information of the product is: 1 H NMR (600MHz, CDCl3), δ, ppm: 1.52 (d, J = 7.2Hz, 3H, CH3), 2.14 (s, 3H, CH3), 5.91 (q, J = 7.2Hz, 1H, CH), 7.14-7.16 (m, 2H, ArH), 7.96-7.99 (m, 2H, ArH); 13 CNMR (150MHz, CDCl3), δ, ppm: 17.2, 20.9, 71.2, 116.1 (d, J = 21.0Hz), 130.9 (d, J = 3.0Hz), 131.3 (d, J = 9.0Hz), 166.1 (d, J = 255.0Hz), 170.5, 195.5; 19 F NMR (564MHz, CDCl3), δ, ppm: -104.0. The above results show that the structure of the product is consistent with the expected one.

[0066] Example 8

[0067] This embodiment provides a method for preparing an α-acyloxy ketone compound 3h, wherein the structural formula of the α-acyloxy ketone compound 3h is Its CAS number is 169295-49-2, and its synthesis steps are as follows:

[0068] 0.30mmol 2-hydroxy-1-(4-chlorophenyl)propan-1-one and 0.60mmol (0.0492g) 2-methylimidazole were added to 3mL acetic anhydride, and the mixture was stirred under reflux at 120°C for 10 hours. After the reaction was completed, the remaining acetic anhydride was removed by distillation under reduced pressure. The reactants were completely transferred to a separatory funnel, extracted three times with dichloromethane (15mL), washed with saturated brine, the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by a rotary evaporator. The crude product was purified and separated by silica gel column chromatography to obtain α-acyloxy ketone compound 3h (colorless oily liquid, 51.5mg, yield 76%).

[0069] The NMR information of the product is:1 H NMR (600MHz, CDCl3), δ, ppm: 1.51 (d, J = 6.6Hz, 3H, CH3), 2.13 (s, 3H, CH3), 5.88 (q, J = 7.2Hz, 1H, CH), 7.44 (d, J = 8.4Hz, 2H, ArH), 7.87 (d, J = 8.4Hz, 2H, ArH); 13 C NMR (150 MHz, CDCl3), δ, ppm: 17.1, 20.8, 71.4, 129.3, 130.0, 132.8, 140.2, 170.5, 195.9. The above results show that the structure of the product is consistent with the expected one.

[0070] Example 9

[0071] This embodiment provides a method for preparing an α-acyloxy ketone compound 3i, wherein the structural formula of the α-acyloxy ketone compound 3i is Its CAS number is 200353-83-9, and its synthesis steps are as follows:

[0072] 0.30mmol 2-hydroxy-1-(4-bromophenyl)propan-1-one and 0.60mmol (0.0492g) 2-methylimidazole were added to 3mL acetic anhydride, and the mixture was stirred under reflux at 120°C for 10 hours. After the reaction was completed, the remaining acetic anhydride was removed by distillation under reduced pressure. The reactants were completely transferred to a separatory funnel, extracted three times with dichloromethane (15mL), washed with saturated brine, the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by a rotary evaporator. The crude product was purified and separated by silica gel column chromatography to obtain α-acyloxy ketone compound 3i (colorless oily liquid, 59.9mg, yield 74%).

[0073] The NMR information of the product is: 1 H NMR (600MHz, CDCl3), δ, ppm: 1.50 (d, J = 6.6Hz, 3H, CH3), 2.12 (s, 3H, CH3), 5.87 (q, J = 7.2Hz, 1H, CH), 7.61 (d, J = 8.4Hz, 2H, ArH), 7.89 (d, J = 8.4Hz, 2H, ArH); 13 C NMR (150 MHz, CDCl3), δ, ppm: 17.1, 20.8, 71.4, 128.9, 130.0, 132.2, 133.2, 170.5, 196.1. The above results show that the structure of the product is consistent with the expected one.

[0074] Example 10

[0075] This embodiment provides a method for preparing an α-acyloxy ketone compound 3j, wherein the structural formula of the α-acyloxy ketone compound 3j is The synthesis steps are as follows:

[0076] 0.30mmol 1-(3-methoxyphenyl)-2-hydroxyethanone and 0.60mmol (0.0492g) 2-methylimidazole were added to 3mL acetic anhydride, and the mixture was stirred under reflux at 120°C for 10 hours. After the reaction was completed, the remaining acetic anhydride was removed by distillation under reduced pressure. The reactants were completely transferred to a separatory funnel, extracted three times with dichloromethane (15mL), washed with saturated brine, the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The crude product was purified and separated by silica gel column chromatography to obtain α-acyloxy ketone compound 3j (colorless oily liquid, 53.3mg, yield 80%).

[0077] The NMR and mass spectrometry information of the product are: 1 H NMR (600MHz, CDCl3), δ, ppm: 1.51 (d, J = 6.6Hz, 3H, CH3), 2.13 (s, 3H, CH3), 3.84 (s, 3H, OCH3), 5.92 (q, J = 7. 2Hz,1H,CH),7.11-7.13(m,1H,ArH),7.35-7.39(m,1H,ArH),7.45(s,1H,ArH),7.50(d,J=7.8Hz,2H,ArH); 13 C NMR (150MHz, CDCl3), δ, ppm: 17.3, 20.8, 55.6, 71.6, 112.9, 120.2, 121.0, 129.9, 135.8, 160.0, 170.5, 196.8; ESI-HRMS, m / z: Calcd for C 12 H 15 O4[M+H] + :223.0965,Found:223.0963. The above results show that the structure of the product is consistent with the expected one.

[0078] Embodiment 11

[0079] This embodiment provides a method for preparing an α-acyloxy ketone compound 3k, wherein the structural formula of the α-acyloxy ketone compound 3k is Its CAS number is 2459909-06-7, and its synthesis steps are as follows:

[0080] 0.30mmol 1-(3-fluorophenyl)-2-hydroxyethanone and 0.60mmol (0.0492g) 2-methylimidazole were added to 3mL acetic anhydride, and the mixture was stirred under reflux at 120°C for 10 hours. After the reaction was completed, the remaining acetic anhydride was removed by distillation under reduced pressure. The reactants were completely transferred to a separatory funnel, extracted three times with dichloromethane (15mL), washed with saturated brine, the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by a rotary evaporator. The crude product was purified and separated by silica gel column chromatography to obtain α-acyloxy ketone compound 3k (colorless oily liquid, 39.1mg, yield 62%).

[0081] The NMR information of the product is: 1 H NMR (600MHz, CDCl3), δ, ppm: 1.52 (d, J=7.2Hz, 3H, CH3), 2.13 (s, 3H, CH3), 5.87 (q, J=7.2Hz, 1H, CH) ,7.27-7.30(m,1H,ArH),7.44-7.47(m,1H,ArH),7.61-7.63(m,1H,ArH),7.71(d,J=7.8Hz,2H,ArH); 13 C NMR (150MHz, CDCl3), δ, ppm: 17.1, 20.8, 71.6, 115.4 (d, J = 22.5Hz), 120.8 (d, J = 21.0Hz), 124 .2(d,J=3.0Hz),130.6(d,J=7.5Hz),136.5(d,J=6.0Hz),163.0(d,J=247.5Hz),170.5,195.9; 19 F NMR (564MHz, CDCl3), δ, ppm: -111.3. The above results show that the structure of the product is consistent with the expected one.

[0082] Example 12

[0083] This embodiment provides a method for preparing an α-acyloxy ketone compound 31, wherein the structural formula of the α-acyloxy ketone compound 31 is Its CAS number is 376346-55-3, and its synthesis steps are as follows:

[0084] 0.30mmol 1-(3-chlorophenyl)-2-hydroxyethanone and 0.60mmol (0.0492g) 2-methylimidazole were added to 3mL acetic anhydride, and the mixture was stirred under reflux at 120°C for 10 hours. After the reaction was completed, the remaining acetic anhydride was removed by distillation under reduced pressure. The reactants were completely transferred to a separatory funnel, extracted three times with dichloromethane (15mL), washed with saturated brine, the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by a rotary evaporator. The crude product was purified and separated by silica gel column chromatography to obtain α-acyloxy ketone compound 31 (colorless oily liquid, 47.5mg, yield 70%).

[0085] The NMR information of the product is: 1 H NMR (600MHz, CDCl3), δ, ppm: 1.51 (d, J=6.6Hz, 3H, CH3), 2.13 (s, 3H, CH3), 5.86 (q, J=7.2Hz, 1H, CH ),7.40-7.43(m,1H,ArH),7.55(d,J=7.8Hz,1H,ArH),7.79(d,J=7.8Hz,1H,ArH),7.90(s,1H,ArH); 13 C NMR (150 MHz, CDCl3), δ, ppm: 17.1, 20.8, 71.5, 126.7, 128.6, 130.2, 133.6, 135.3, 136.1, 170.5, 195.9. The above results show that the structure of the product is consistent with the expected one.

[0086] Embodiment 13

[0087] This embodiment provides a method for preparing an α-acyloxy ketone compound 3m, wherein the structural formula of the α-acyloxy ketone compound 3m is Its CAS number is 221908-59-4, and its synthesis steps are as follows:

[0088] 0.30mmol 1-(2-thienyl)-2-hydroxyethanone and 0.60mmol (0.0492g) 2-methylimidazole were added to 3mL acetic anhydride, and the mixture was stirred under reflux at 120°C for 10 hours. After the reaction was completed, the remaining acetic anhydride was removed by distillation under reduced pressure. The reactants were completely transferred to a separatory funnel, extracted three times with dichloromethane (15mL), washed with saturated brine, the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by a rotary evaporator. The crude product was purified and separated by silica gel column chromatography to obtain α-acyloxy ketone compound 3m (colorless oily liquid, 48.7mg, yield 82%).

[0089] The NMR information of the product is: 1H NMR (600MHz, CDCl3), δ, ppm: 1.56 (d, J=7.2Hz, 3H, CH3), 2.14 (s, 3H, CH3), 5.73 (q, J=7.2H z,1H,CH),7.14-7.16(m,1H,ArH),7.69(d,J=4.8Hz,1H,ArH),7.80(d,J=4.8Hz,1H,ArH); 13 C NMR (150 MHz, CDCl3), δ, ppm: 17.8, 20.9, 72.4, 128.4, 132.8, 134.6, 140.6, 170.4, 189.9. The above results show that the structure of the product is consistent with the expected one.

[0090] Embodiment 14

[0091] This embodiment provides a method for preparing an α-acyloxy ketone compound 3n, wherein the structural formula of the α-acyloxy ketone compound 3n is Its CAS number is 54034-47-8, and its synthesis steps are as follows:

[0092] 0.30mmol 2-hydroxypropiophenone and 0.60mmol (0.0492g) 2-methylimidazole were added to 3mL acetic anhydride, and the mixture was stirred under reflux at 120°C for 10 hours. After the reaction was completed, the remaining acetic anhydride was removed by distillation under reduced pressure. The reactants were completely transferred to a separatory funnel, extracted three times with dichloromethane (15mL), washed with saturated brine, the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by a rotary evaporator. The crude product was purified and separated by silica gel column chromatography to obtain α-acyloxy ketone compound 3n (colorless oily liquid, 53.8mg, yield 87%).

[0093] The NMR information of the product is: 1 H NMR (600MHz, CDCl3), δ, ppm: 1.01 (t, J = 7.8Hz, 3H, CH3), 1.81-1.97 (m, 2H, CH2), 2.15 (s, 3H, CH3), 5 .80-5.82(m,1H,CH),7.45-7.48(m,2H,ArH),7.57(t,J=7.2Hz,1H,ArH),7.93(d,J=7.2Hz,2H,ArH); 13 C NMR (150 MHz, CDCl3), δ, ppm: 10.0, 20.8, 24.9, 76.5, 128.5, 128.9, 133.6, 135.0, 170.8, 196.7. The above results show that the structure of the product is consistent with the expected one.

[0094] Embodiment 15

[0095] This embodiment provides a method for preparing an α-acyloxy ketone compound 3o, wherein the structural formula of the α-acyloxy ketone compound 3o is Its CAS number is 104426-39-3, and its synthesis steps are as follows:

[0096] 0.30mmol 2-hydroxy-1-phenylpentane-1-one and 0.60mmol (0.0492g) 2-methylimidazole were added to 3mL acetic anhydride, and the mixture was stirred under reflux at 120°C for 10 hours. After the reaction was completed, the remaining acetic anhydride was removed by distillation under reduced pressure. The reactants were completely transferred to a separatory funnel, extracted three times with dichloromethane (15mL), washed with saturated brine, the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by a rotary evaporator. The crude product was purified and separated by silica gel column chromatography to obtain α-acyloxy ketone compound 3o (colorless oily liquid, 46.9mg, yield 71%).

[0097] The NMR information of the product is: 1 H NMR (600MHz, CDCl3), δ, ppm: 0.93 (t, J=7.8Hz, 3H, CH3), 1.45-1.50 (m, 2H, CH2), 1.79-1.83 (m, 2H, CH2), 2.13 (s ,3H,CH3),5.85-5.87(m,1H,CH),7.44-7.47(m,2H,ArH),7.56(t,J=7.2Hz,1H,ArH),7.92(d,J=7.2Hz,2H,ArH); 13 C NMR (150 MHz, CDCl3), δ, ppm: 13.8, 18.9, 20.7, 33.5, 75.2, 128.4, 128.8, 133.6, 134.8, 170.7, 196.8. The above results show that the structure of the product is consistent with the expected one.

[0098] Example 16

[0099] This embodiment provides a method for preparing an α-acyloxy ketone compound 3p, wherein the structural formula of the α-acyloxy ketone compound 3p is Its CAS number is 53901-50-1, and its synthesis steps are as follows:

[0100] 0.30mmol benzoin and 0.60mmol (0.0492g) 2-methylimidazole were added to 3mL propionic anhydride, and the mixture was stirred under reflux at 120°C for 10 hours. After the reaction was completed, the remaining propionic anhydride was removed by distillation under reduced pressure. The reactants were completely transferred to a separatory funnel, extracted three times with dichloromethane (15mL), washed with saturated brine, the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by a rotary evaporator. The crude product was purified and separated by silica gel column chromatography to obtain α-acyloxy ketone compound 3p (colorless oily liquid, 70.8mg, yield 88%).

[0101] The NMR information of the product is: 1 H NMR (600MHz, CDCl3), δ, ppm: 1.19 (t, J=7.8Hz, 3H, CH3), 2.44-2.58 (m, 2H, CH2), 6.87 (s, 1H, CH), 7.32 -7.41(m,5H,ArH),7.47(d,J=7.8Hz,2H,ArH),7.51(t,J=7.2Hz,1H,ArH),7.94(d,J=7.2Hz,2H,ArH); 13 C NMR (150 MHz, CDCl3), δ, ppm: 9.1, 27.5, 77.6, 128.7, 128.8, 128.9, 129.2, 129.4, 133.6, 133.8, 134.8, 174.1, 194.1. The above results show that the structure of the product is consistent with the expectation.

[0102] Embodiment 17

[0103] This embodiment provides a method for preparing an α-acyloxy ketone compound 3q, wherein the structural formula of the α-acyloxy ketone compound 3q is Its CAS number is 50889-03-7, and its synthesis steps are as follows:

[0104] 0.30mmol benzoin and 0.60mmol (0.0492g) 2-methylimidazole were added to 3mL isobutyric anhydride, and the mixture was stirred under reflux at 120°C for 10 hours. After the reaction was completed, the remaining isobutyric anhydride was removed by vacuum distillation. The reactants were completely transferred to a separatory funnel, extracted three times with dichloromethane (15mL), washed with saturated brine, the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by a rotary evaporator. The crude product was purified and separated by silica gel column chromatography to obtain α-acyloxy ketone compound 3q (white solid, mp: 75-77°C, 71.0mg, yield 84%).

[0105] The NMR information of the product is: 1H NMR (600MHz, CDCl3), δ, ppm: 1.22 (d, J = 7.2Hz, 3H, CH3), 1.38 (d, J = 7.2Hz, 3H, CH3), 2.70-2.77 (m, 1 H,CH),6.86(s,1H,CH),7.33-7.41(m,5H,ArH),7.48-7.51(m,3H,ArH),7.95(d,J=7.2Hz,2H,ArH); 13 C NMR (150MHz, CDCl3), δ, ppm: 18.8, 19.1, 33.9, 77.4, 128.6, 128.7, 128.9, 129.1, 129.3, 133.5, 133.8, 134.8, 176.7, 194.1. The X-ray single crystal diffraction pattern of the product is shown in the attached Figure 1 The above results show that the structure of the product is consistent with the expected one.

[0106] Embodiment 18

[0107] This embodiment provides a method for preparing an α-acyloxy ketone compound 3r, wherein the structural formula of the α-acyloxy ketone compound 3r is Its CAS number is 51891-90-8, and its synthesis steps are as follows:

[0108] 0.30mmol benzoin and 0.60mmol (0.0492g) 2-methylimidazole were added to 3mL pivalic anhydride, and the mixture was stirred under reflux at 120°C for 10 hours. After the reaction was completed, the remaining pivalic anhydride was removed by distillation under reduced pressure. The reactants were completely transferred to a separatory funnel, extracted three times with dichloromethane (15mL), washed with saturated brine, the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by a rotary evaporator. The crude product was purified and separated by silica gel column chromatography to obtain α-acyloxy ketone compound 3r (white solid, mp: 107-109°C, 71.9mg, yield 81%).

[0109] The NMR information of the product is: 1 H NMR (600MHz, CDCl3), δ, ppm: 1.29 (s, 9H, 3CH3), 6.80 (s, 1H, CH), 7.33-7.42 (m, 5H, Ar H),7.47(d,J=7.8Hz,2H,ArH),7.51(t,J=7.2Hz,1H,ArH),7.94(d,J=7.2Hz,2H,ArH); 13C NMR (150 MHz, CDCl3), δ, ppm: 27.2, 38.9, 77.4, 128.4, 128.7, 128.9, 129.1, 129.2, 133.5, 134.0, 135.0, 178.2, 194.4. The above results show that the structure of the product is consistent with the expectation.

[0110] Embodiment 19

[0111] This embodiment provides a method for preparing an α-acyloxy ketone compound 3s, wherein the structural formula of the α-acyloxy ketone compound 3s is Its CAS number is 50889-04-8, and its synthesis steps are as follows:

[0112] 0.30mmol benzoin and 0.60mmol (0.0492g) 2-methylimidazole were added to 3mL n-hexanoic anhydride, and the mixture was stirred under reflux at 120°C for 10 hours. After the reaction was completed, the remaining n-hexanoic anhydride was removed by vacuum distillation. The reactants were completely transferred to a separatory funnel, extracted three times with dichloromethane (15mL), washed with saturated brine, the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by a rotary evaporator. The crude product was purified and separated by silica gel column chromatography to obtain α-acyloxy ketone compound 3s (colorless oily liquid, 61.8mg, yield 73%).

[0113] The NMR information of the product is: 1 H NMR (600MHz, CDCl3), δ, ppm: 0.98 (t, J = 7.2Hz, 3H, CH3), 1.69-1.75 (m, 2H, CH2), 2.40-2.51 (m, 2H, CH2), 6.86 (s, 1 H,CH),7.34-7.41(m,5H,ArH),7.46(d,J=7.2Hz,2H,ArH),7.51(t,J=7.8Hz,1H,ArH),7.94(d,J=7.8Hz,2H,ArH); 13 C NMR (150 MHz, CDCl3), δ, ppm: 13.8, 18.5, 36.0, 77.5, 128.7, 128.9, 129.2, 129.4, 133.6, 133.8, 134.9, 173.3, 194.1. The above results show that the structure of the product is consistent with the expectation.

[0114] Embodiment 20

[0115] This embodiment provides a method for preparing an α-acyloxy ketone compound 3t, wherein the structural formula of the α-acyloxy ketone compound 3t is Its CAS number is 51891-89-5, and its synthesis steps are as follows:

[0116] 0.30mmol benzoin and 0.60mmol (0.0492g) 2-methylimidazole were added to 3mL chloroacetic anhydride, and the mixture was stirred under reflux at 120°C for 10 hours. After the reaction was completed, the remaining chloroacetic anhydride was removed by distillation under reduced pressure. The reactants were completely transferred to a separatory funnel, extracted three times with dichloromethane (15mL), washed with saturated brine, the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed by a rotary evaporator. The crude product was purified and separated by silica gel column chromatography to obtain α-acyloxy ketone compound 3t (colorless oily liquid, 70.0mg, yield 81%).

[0117] The NMR information of the product is: 1 H NMR (600MHz, CDCl3), δ, ppm: 4.19-4.29 (dd, J1=42.6Hz, J2=15.0Hz, 2H, CH2), 6.94 (s, 1H, CH), 7.37- 7.41(m,5H,ArH),7.47(d,J=7.8Hz,2H,ArH),7.52(t,J=7.2Hz,1H,ArH),7.92(d,J=7.2Hz,2H,ArH); 13 C NMR (150 MHz, CDCl3), δ, ppm: 40.8, 79.2, 128.8, 128.9, 129.0, 129.4, 129.8, 133.0, 133.8, 134.3, 167.0, 192.8. The above results show that the structure of the product is consistent with the expected.

[0118] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be equivalent replacement methods and are included in the protection scope of the present invention.

Claims

1. A method for preparing an α-acyloxy ketone compound, characterized in that: The method comprises the following steps: reacting a hydroxyketone compound represented by formula (I) with an acid anhydride represented by formula (II) under the action of an imidazole catalyst to obtain an α-acyloxy ketone compound represented by formula (III), and the reaction formula is as follows: Among them, R 1 is selected from aryl or aralkyl; R 2 is selected from aryl, aralkyl or alkyl; R 3 It is an alkyl group.

2. The method for preparing an α-acyloxy ketone compound according to claim 1, characterized in that: The R 1 or R 2 The aryl groups are independently substituted or unsubstituted mononuclear aryl groups; when R 1 or R 2 When the aryl group is a substituted mononuclear aryl group, the substituents are independently selected from C1-C7 alkyl, C1-C7 alkoxy, halogen, cyano, acetyl, nitro, alkoxycarbonyl or ester.

3. The method for preparing an α-acyloxy ketone compound according to claim 2, characterized in that: The R 1 is selected from the group consisting of phenyl, 4-methylphenyl, 4-ethylphenyl, 4-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 3-fluorophenyl, 3-chlorophenyl, 3-methoxyphenyl, and 2-thienyl; wherein R 2 is selected from the group consisting of phenyl, 4-methylphenyl, 4-ethylphenyl, 4-methoxyphenyl, methyl, ethyl, and n-propyl; 3 Selected from methyl, ethyl, n-propyl, isopropyl, tert-butyl, chloroethyl.

4. The method for preparing an α-acyloxy ketone compound according to claim 3, characterized in that: The α-acyloxy ketone compound is selected from one of Formula 3a to Formula 3t:

5. The method for preparing an α-acyloxy ketone compound according to claim 1, characterized in that: The imidazole catalyst is selected from at least one of 2-methylimidazole, 2-ethylimidazole, 2-ethyl-4-methylimidazole and 2-phenylimidazole.

6. The method for preparing an α-acyloxy ketone compound according to claim 1, characterized in that: The reaction time of the reaction is 9 to 13 hours.

7. The method for preparing an α-acyloxy ketone compound according to claim 1, characterized in that: The reaction temperature of the reaction is 100-150°C.

8. The method for preparing an α-acyloxy ketone compound according to claim 1, characterized in that: The molar ratio of the hydroxyketone compound to the imidazole catalyst is 1:(1-4).

9. The method for preparing an α-acyloxy ketone compound according to claim 1, characterized in that: The usage ratio of the hydroxyketone compound to the acid anhydride is 1 mmol: (7-15) mL.

10. The method for preparing an α-acyloxy ketone compound according to claim 1, characterized in that: The method comprises the following steps: reacting a hydroxyketone compound as shown in formula (I) and an acid anhydride as shown in formula (II) under the action of an imidazole catalyst to obtain a product mixture, removing the acid anhydride, and purifying to obtain an α-acyloxy ketone compound as shown in formula (III); the purification comprises extracting the product mixture in sequence, washing the organic phase, drying and separating by column chromatography.

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