Preparation method of alpha-alkyl ketone derivative

Abstract

The invention belongs to the technical field of organic chemistry, and particularly discloses a preparation method of an alpha-alkyl ketone derivative, which comprises the following steps: stirring 1-substituted ethanol, aryl primary alcohol, methanol and alkali at 100-140 DEG C to react for 12-36 hours under the protection of inert gas by taking iron cyclopentadienone as a catalyst, so as to obtain the alpha-alkyl ketone derivative. According to the method, iron cyclopentadienone is used as a catalyst, and under the action of alkali, iron cyclopentadienone can efficiently catalyze a three-component hydrogen borrowing reaction of 1-substituted ethanol, aryl primary alcohol and methanol to obtain the alpha-alkyl ketone derivative. Compared with the prior art, the method has the advantages of low energy consumption, high atom economy, environment friendliness, high safety, easiness in industrialization and the like.

Description

Technical Field

[0001] The invention belongs to the technical field of organic chemistry, and specifically relates to a method for preparing alpha-alkyl ketone derivatives. Background Art

[0002] In the field of pharmaceutical chemicals, methylation reactions are widely used in the synthesis of APIs, pharmaceutical intermediates, and the structural modification of active drug molecules. Using methanol as a methylation agent to construct CC bonds by using hydrogen or hydrogen transfer mechanisms has become a very important method, which has the advantages of being green, environmentally friendly, and having high atomic utilization. Among the existing drugs, tolperisone and ethidone are both central muscle relaxants. The chemical name of tolperisone is 2,4'-dimethyl-3-piperidinylpropiophenone, and the chemical name of ethidone is 4'-ethyl-2-methyl-3-piperidinylpropiophenone. Both have methyl groups at the α position and belong to α-alkyl ketone compounds.

[0003] The main method for synthesizing α-alkyl ketones traditionally uses halides and acetophenone as substrates, which have low atomic utilization rates and most halides are toxic and harmful. In 2017, the Kundu research group (Organic Letters, 2017, 19 (18): 4750-4753) reported a three-component series alkylation reaction system of ketones, alcohols and methanol catalyzed by non-phosphine-based catalyst Ru-1. The system uses Ru complex as a catalyst to obtain α-alkylation products of methylene ketones with a yield of 52-81%. However, the reaction uses precious metal ruthenium as a catalyst, which is costly and difficult to industrialize. In recent years, the hydrogen borrowing reaction catalyzed by abundant metallic iron has the characteristics of low energy consumption, high atom economy and strong practicality, and is an important method for obtaining α-alkyl ketone derivatives. Summary of the invention

[0004] In order to solve the above problems, the present invention provides a method for preparing α-alkyl ketone derivatives. The method uses cyclopentadienone iron as a catalyst. Under the action of a base, the cyclopentadienone iron can efficiently catalyze 1-substituted ethanol with a primary aromatic alcohol and methanol to undergo a three-component hydrogen borrowing reaction to obtain α-alkyl ketone derivatives.

[0005] The technical solution of the present invention is as follows:

[0006] The present invention discloses a method for preparing an α-alkyl ketone derivative, characterized in that the reaction formula is as follows, comprising the following steps: under the protection of an inert gas, using cyclopentadienone iron as shown in formula (VI) as a catalyst, placing a mixture of 1-substituted ethanol as shown in formula (I), an aromatic primary alcohol as shown in formula (II), methanol and a base, stirring and reacting at 100-140° C. for 12-36 hours to obtain an α-alkyl ketone derivative as shown in formula (III);

[0007] Wherein, in formula (I), R is phenyl, substituted phenyl, naphthyl or cyclopropyl, and the substituent in the substituted phenyl is alkyl, alkoxy, halogen or haloalkyl; in formula (II), R 1 It is phenyl, substituted phenyl or heterocyclic aryl, and the substituent in the substituted phenyl is alkyl, alkoxy, halogen or halogenated alkyl.

[0008]

[0009] In one embodiment of the present invention, preferably, the process further comprises adding water to quench the reaction after the reaction is completed, extracting with an organic solvent, concentrating the separated organic solvent layer under reduced pressure, and then separating by column chromatography to obtain an α-alkyl ketone derivative as shown in (III).

[0010] In one embodiment of the present invention, preferably, the organic solvent used for the extraction is ethyl acetate or dichloromethane.

[0011] In one embodiment of the present invention, preferably, the solvent used for column chromatography separation is petroleum ether / ethyl acetate, and the volume ratio thereof is 10:1 to 50:1.

[0012] In one embodiment of the present invention, preferably, the molar ratio of the 1-substituted ethanol shown in formula (I), methanol, the primary aromatic alcohol shown in formula (II), the base and the cyclopentadienone iron shown in formula (VI) is 1:1.5~10:1.5~5:1~5:0.02~0.1.

[0013] In one embodiment of the present invention, preferably, the molar ratio of the 1-substituted ethanol shown in formula (I), methanol, the primary aromatic alcohol shown in formula (II), the base and the cyclopentadienone iron shown in formula (VI) is 1:3:4:3:0.02.

[0014] In one embodiment of the present invention, preferably, the base is one or more of potassium phosphate, potassium carbonate, potassium tert-butoxide or cesium carbonate.

[0015] In one embodiment of the present invention, preferably, the base is potassium phosphate.

[0016] Compared with the prior art, the present invention has the following beneficial effects:

[0017] The invention discloses a method for preparing an α-alkyl ketone derivative, using cyclopentadienone iron as a catalyst. Compared with the hydrogen borrowing reaction catalyzed by precious metals, the method uses relatively cheap metal iron to catalyze hydrogen borrowing. Under the action of a base, the cyclopentadienone iron can efficiently catalyze 1-substituted ethanol, primary aromatic alcohol and methanol to undergo a three-component hydrogen borrowing reaction to obtain an α-alkyl ketone derivative. Compared with the prior art, the method has the characteristics of low energy consumption, high atomic economy, green environmental protection, high safety and easy industrialization. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 2-methyl-1,3-diphenylpropan-1-one (III-3aa) of Example 1 of the present invention 1 H NMR spectrum;

[0019] Figure 2 2-methyl-3-phenyl-1-(p-tolyl)propan-1-one (III-3ba) of Example 2 of the present invention 1 HNMR spectrum;

[0020] Figure 3 1-(4-methoxyphenyl)-2-methyl-3-phenylpropan-1-one (III-3ca) of Example 3 of the present invention 1 H NMR spectrum;

[0021] Figure 4 1-(4-(tert-butyl)phenyl)-2-methyl-3-phenylpropan-1-one (III-3da) of Example 4 of the present invention 1 H NMR spectrum;

[0022] Figure 5 1-(4-bromophenyl)-2-methyl-3-phenylpropan-1-one (III-3ia) of Example 9 of the present invention 1 HNMR spectrum;

[0023] Figure 6 2-methyl-3-phenyl-1-(4-(trifluoromethyl)phenyl)propan-1-one (III-3ja) of Example 10 of the present invention 1 H NMR spectrum;

[0024] Figure 7 The cyclopentadienone iron catalyst shown in the present invention (VI) 1 H NMR spectrum. DETAILED DESCRIPTION

[0025] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific embodiments of the present invention are described in detail below with reference to the accompanying drawings.

[0026] Many specific details are set forth in the following description to facilitate a full understanding of the present invention. However, the present invention can be implemented in many other ways than those described herein, and those skilled in the art can make similar generalizations without violating the connotation of the present invention, so the present invention is not limited to the specific implementation disclosed below.

[0027] The raw materials used in the present invention can be obtained by commercial means, wherein the cyclopentadienone iron catalyst shown in formula (VI) can be prepared by the following method:

[0028]

[0029] Under nitrogen protection, compound V (1.28 g, 5.0 mmol), methanol (5 mL) and compound VI (710 mg, 5.0 mmol) were added to a pressure tube equipped with a magnetic pole. After heating and reflux reaction for about 12 hours, the mixture was cooled, quenched with water (30 mL), extracted with ethyl acetate (30 mL x 3), and the organic layer was concentrated. Subsequently, under nitrogen protection, the concentrated organic matter was added to a Schlenk tube equipped with diferrononyl (1.82 g, 5.0 mmol) and toluene (dried and degassed, 10 mL), heated and refluxed for about 24 hours, cooled, transferred to a round-bottom flask, washed several times with toluene (3 x 10 mL), and the mixture was concentrated in vacuo; the residue was purified by silica gel column chromatography (dichloromethane / methanol = 30:1) to obtain an orange-yellow solid (588.4 mg, 56%).

[0030] Structural characterization of catalyst VI: yellow solid, such as Figure 7 As shown, 1 HNMR(400MHz,CDCl3 )δ7.65(d,J=7.4Hz,2H),7.60(d,J=7.4Hz,2H),7.42–7.33(m,6H),3.18(d,J=9.6Hz,1H),2.51(td,J=8.5,4.7Hz,1H ),2.43(s,3H),2.33(s,3H),2.28(d,J=3.3Hz,1H),2.17(d,J=9.4Hz,1H),1.88(d,J=9.5Hz,2H),1.36–1.27(m,4H); 13 CNMR(100MHz,CDCl3 )δ210.3,165.0,131.9(d,J=11.9Hz),128.3(d,J=19.0Hz),127.7(d,J=4.4Hz),123.7 ,108.3,73.1,69.1,63.4,60.6,37.9,35.5,28.7(d,J=4.5Hz),24.3(d,J=7.5Hz).ppm; HRMS(ESI) calculated for C 29 H 29 FeN2O4[M+H] + :524.1623,found:524.1614.

[0031] Embodiment 1:

[0032]

[0033] Under the protection of argon atmosphere, 1-phenylethanol (61 mg, 0.5 mmol), benzyl alcohol (216 mg, 2.0 mmol), methanol (162 mg, 1.5 mmol), cyclopentadienone iron catalyst (5.3 mg, 2.0 mol%) and potassium phosphate (261 mg, 1.5 mmol) were added to a pressure tube equipped with a magnetic pole, replaced with argon, and placed at 120°C for 24 hours. After the reaction was completed, it was quenched with water (10 mL) and extracted with ethyl acetate (10 mL x 3). The separated organic layer was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 30:1) to obtain 101 mg of 2-methyl-1,3-diphenylpropan-1-one (III-3aa) product, with a yield of 90%.

[0034] Structural characterization of 2-methyl-1,3-diphenylpropan-1-one (III-3aa): Colorless oil; 90% yield, 1 H NMR (400MHz, CDCl3) δ7.98–7.96(m,2H),7.59–7.56(m,1H),7.50–7.46(m,J=7.4Hz,2H),7.33–7.29(m,2H),7.25– 7.20(m,3H),3.84–3.75(m,1H),3.22(dd,J=13.8,6.2Hz,1H),2.74(dd,J=13.6,8.0Hz,1H),1.25(d,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ203.8,140.0,136.5,132.9,129.1,128.6,128.4,128.3,126.2,42.8,39.4,17.4ppm; HRMS (ESI) calculated for C 16 H 17 O[M+H] + :225.1201,found:225.1203.

[0035] At the same time, the single factor variable method was used to investigate the effects of reaction stability, reaction time, type of alkali and amount of raw materials on the reaction. The remaining experimental processes and parameters were the same as those in Example 1. The reaction results are shown in Table 1:

[0036] Table 1

[0037]

[0038]

[0039] Embodiment 2:

[0040]

[0041] Under the protection of argon atmosphere, 1-p-methylphenylethanol (68 mg, 0.5 mmol), benzyl alcohol (216 mg, 2.0 mmol), methanol (162 mg, 1.5 mmol), cyclopentadienone iron catalyst (5.3 mg, 2.0 mol%) and potassium phosphate (261 mg, 1.5 mmol) were added to a pressure tube equipped with a magnetic pole, replaced with argon, and placed at 120°C for 24 hours. After the reaction was completed, it was quenched with water (10 mL) and extracted with ethyl acetate (10 mL x 3). The separated organic layer was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 30:1) to obtain 101 mg of 2-methyl-3-phenyl-1-(p-tolyl)propan-1-one (III-3ba) product, with a yield of 85%.

[0042] Structural characterization of 2-methyl-3-phenyl-1-(p-tolyl)propan-1-one (III-3ba): Colorless oil; 85% yield, 1 H NMR (400MHz, CDCl3) δ7.89–7.86(m,2H),7.30–7.27(m,4H),7.24–7.19(m,3H),3.81–3.72(m,1H) ,3.20(dd,J=13.8,6.2Hz,1H),2.74(dd,J=13.6,8.0Hz,1H),2.43(s,3H),1.23(d,J=6.8Hz,3H); 13 C NMR(100MHz, CDCl3)δ203.4,143.7,140.1,133.9,129.4,129.1,128.5,128.4,126.2,42.6,39.4,21.6,17.5ppm; HRMS(ESI)calculated forC 17 H 19 O[M+H] + :239.1358,found:239.1355.

[0043] Embodiment 3:

[0044]

[0045] Under the protection of argon atmosphere, 1-p-methoxyphenylethanol (76 mg, 0.5 mmol), benzyl alcohol (216 mg, 2.0 mmol), methanol (162 mg, 1.5 mmol), cyclopentadienone iron catalyst (5.3 mg, 2.0 mol%) and potassium phosphate (261 mg, 1.5 mmol) were added to a pressure tube equipped with a magnetic pole, replaced with argon, and placed at 120°C for 24 hours. After the reaction was completed, it was quenched with water (10 mL) and extracted with ethyl acetate (10 mL x 3). The separated organic layer was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 30:1) to obtain 102 mg of 1-(4-methoxyphenyl)-2-methyl-3-phenylpropan-1-one (III-3ca) product, with a yield of 80%.

[0046] Structural characterization of 1-(4-methoxyphenyl)-2-methyl-3-phenylpropan-1-one (III-3ca): Colorless oil; 80% yield, 1 H NMR(400MHz, CDCl3)δ7.96(d,J=8.8Hz,2H),7.31–7.27(m,2H),7.24–7.19(m,3H),6.97–6.93(m,2H),3.87( s,3H),3.80–3.78(m,1H),3.20(dd,J=13.6,6.4Hz,1H),2.72(dd,J=13.6,7.6Hz,1H),1.22(d,J=6.8Hz,3H); 13 C NMR (100MHz, CDCl3) δ202.3,163.4,140.1,130.6,129.4,129.1,128.4,126.2,113.8,55.5,42.4,39.5,17.6ppm; HRMS (ESI) calculated for C 17 H 19 O2[M+H] + :255.1307,found:255.1309.

[0047] Embodiment 4:

[0048]

[0049] Under the protection of argon atmosphere, 1-p-tert-butylphenylethanol (89 mg, 0.5 mmol), benzyl alcohol (216 mg, 2.0 mmol), methanol (162 mg, 1.5 mmol), cyclopentadienone iron catalyst (5.3 mg, 2.0 mol%) and potassium phosphate (261 mg, 1.5 mmol) were added to a pressure tube equipped with a magnetic pole, replaced with argon, and placed at 120°C for 24 h. After the reaction was completed, it was quenched with water (10 mL) and extracted with ethyl acetate (10 mL x 3). The separated organic layer was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 30:1) to obtain 116 mg of 1-(4-(tert-butyl)phenyl)-2-methyl-3-phenylpropan-1-one (III-3da) product, with a yield of 83%.

[0050] Structural characterization of 1-(4-(tert-butyl)phenyl)-2-methyl-3-phenylpropan-1-one (III-3da): Colorlessoil; 83% yield, 1 H NMR(400MHz, CDCl3)δ7.89(d,J=8.4Hz,2H),7.47–7.45(m,2H),7.26–7.21(m,2H),7.19–7.15(m,3H),3.78– 3.69(m,1H),3.17(dd,J=13.6,6.4Hz,1H),2.67(dd,J=13.6,8.0Hz,1H),1.33(s,3H),1.19(d,J=6.8Hz,3H); 13 C NMR (100MHz, CDCl3) δ203.3,156.7,140.1,133.8,129.1,128.4,128.3,126.2,125.6,42.7,39.4,35.1,31.1,17.5ppm; HRMS(ESI) calculated for C 20 H 19 O[M+H] + :281.1827,found:281.1829.

[0051] Embodiment 5:

[0052]

[0053] Under the protection of argon atmosphere, 1-m-methylphenylethanol (68 mg, 0.5 mmol), benzyl alcohol (216 mg, 2.0 mmol), methanol (162 mg, 1.5 mmol), cyclopentadienone iron catalyst (5.3 mg, 2.0 mol%) and potassium phosphate (261 mg, 1.5 mmol) were added to a pressure tube equipped with a magnetic pole, replaced with argon, and placed at 120°C for 24 hours. After the reaction was completed, it was quenched with water (10 mL) and extracted with ethyl acetate (10 mL x 3). The separated organic layer was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 30:1) to obtain 89 mg of 2-methyl-3-phenyl-1-(m-tolyl)propan-1-one (III-3ea) product, with a yield of 75%.

[0054] Structural characterization of 2-methyl-3-phenyl-1-(m-tolyl)propan-1-one (III-3ea): Colorless oil; 75% yield, 1 H NMR(400MHz, CDCl3)δ7.76(d,J=8.8Hz,2H),7.40–7.36(m,2H),7.32–7.28(m,2H),7.25–7.20(m,3H),3.82– 3.73(m,1H),3.20(dd,J=13.6,6.4Hz,1H),2.73(dd,J=13.6,7.6Hz,1H),2.43(s,3H),1.23(d,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ204.4,140.1,138.5,136.5,133.7,129.1,128.9,128.5,128.4,126.2,125.5,42.8,39.4,21.4,17.5ppm; HRMS (ESI) calculated for C 16 H 16 BrO[M+H] + :239.1358,found:239.1356.

[0055] Embodiment 6:

[0056]

[0057] Under the protection of argon atmosphere, 1-m-methoxyphenylethanol (76 mg, 0.5 mmol), benzyl alcohol (216 mg, 2.0 mmol), methanol (162 mg, 1.5 mmol), cyclopentadienone iron catalyst (5.3 mg, 2.0 mol%) and potassium phosphate (261 mg, 1.5 mmol) were added to a pressure tube equipped with a magnetic pole, replaced with argon, and placed at 120°C for 24 hours. After the reaction was completed, it was quenched with water (10 mL) and extracted with ethyl acetate (10 mL x 3). The separated organic layer was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 30:1) to obtain 93 mg of 2-methyl-3-phenyl-1-(m-methoxyphenyl)propan-1-one (III-3fa) product, with a yield of 73%.

[0058] Structural characterization of 2-methyl-3-phenyl-1-(m-methoxyphenyl)propan-1-one (III-3fa): Colorless oil; 73% yield, 1 H NMR(400MHz, CDCl3)δ7.53(d,J=7.6Hz,1H),7.48–7.47(m,1H),7.40–7.36(m,1H),7.31–7.27(m,2H),7.27–7.19(m,3H),7.13– 7.10(m,1H),3.87(s,3H),3.79–3.70(m,1H),3.19(dd,J=14.0,6.2Hz,1H),2.71(dd,J=14.0,7.8Hz,1H),1.23(d,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ202.3,163.4,140.2,130.6,129.4,129.1,128.4,126.2,113.8,55.5,42.4,39.6,17.6ppm; HRMS (ESI) calculated for C 17 H 19 O2[M+H] + :255.1307,found:255.1303.

[0059] Embodiment 7:

[0060]

[0061] Under the protection of argon atmosphere, 1-3,4-dimethylphenylethanol (75 mg, 0.5 mmol), benzyl alcohol (216 mg, 2.0 mmol), methanol (162 mg, 1.5 mmol), cyclopentadienone iron catalyst (5.3 mg, 2.0 mol%) and potassium phosphate (261 mg, 1.5 mmol) were added to a pressure tube equipped with a magnetic pole, replaced with argon, and placed at 120°C for 24 hours. After the reaction was completed, it was quenched with water (10 mL) and extracted with ethyl acetate (10 mL x 3). The separated organic layer was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 30:1) to obtain 88 mg of 1-(3,4-dimethylphenyl)-2-methyl-3-phenylpropan-1-one (III-3ga) product, with a yield of 70%.

[0062] Structural characterization of 1-(3,4-dimethylphenyl)-2-methyl-3-phenylpropan-1-one (III-3ga): Colorless oil; 70% yield, 1 H NMR (400MHz, CDCl3) δ7.73–7.65(m,2H),7.30–7.24(m,3H),7.21–7.17(m,3H),3.76–3.66(m,1H) ,3.16(dd,J=14.0,6.2Hz,1H),2.67(dd,J=13.6,8.0Hz,1H),2.30(s,6H),1.18(d,J=6.8Hz,3H); 13 C NMR (100MHz, CDCl3) δ203.7,142.5,140.2,137.0,134.3,129.8,129.5,129.1,128.4,126.1,126.0,42.6,39.4,20.0,19.8,17.6ppm; HRMS(ESI) calculated for C 17 H 19 O[M+H] + :253.1514,found:225.1519.

[0063] Embodiment 8:

[0064]

[0065] Under the protection of argon atmosphere, 1-naphthylethanol (86mg, 0.5mmol), benzyl alcohol (216mg, 2.0mmol), methanol (162mg, 1.5mmol), cyclopentadienone iron catalyst (5.3mg, 2.0mol%) and potassium phosphate (261mg, 1.5mmol) were added to a pressure tube equipped with a magnetic pole. After replacement with argon, the mixture was placed at 120°C for 24h. After the reaction was completed, the mixture was quenched with water (10mL) and extracted with ethyl acetate (10mL x 3). The separated organic layer was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 30:1) to obtain 114mg 2-methyl-1-(naphthyl)-3-phenylpropan-1-one (III-3ha) product, with a yield of 83%.

[0066] Structural characterization of 2-methyl-1-(naphthalen-2-yl)-3-phenylpropan-1-one (III-3ha): Colorless oil; 83% yield, 1 H NMR(400MHz, CDCl3)δ8.40(s,1H),8.01–7.99(m,1H),7.93(d,J=8.0Hz,1H),7.89–7.85(m,2H),7.60–7.52(m,2H),7.29–7.22( m,4H),7.20–7.15(m,1H),3.95–3.87(m,1H),3.23(dd,J=14.0,6.4Hz,1H),2.76(dd,J=13.6,7.0Hz,1H),1.27(d,J=6.8Hz,3H); 13 C NMR (100MHz, CDCl3) δ203.7,140.0,135.5,133.9,132.6,129.8,129.6,129.1,128 .5,128.4,127.7,126.7,126.2,124.2,42.9,39.6,17.7ppm; HRMS(ESI)calculated forC 20 H 19 O[M+H] + :275.1358,found:275.1355.

[0067] Embodiment 9:

[0068]

[0069] Under the protection of argon atmosphere, 1-p-bromophenylethanol (101 mg, 0.5 mmol), benzyl alcohol (216 mg, 2.0 mmol), methanol (162 mg, 1.5 mmol), cyclopentadienone iron catalyst (5.3 mg, 2.0 mol%) and potassium phosphate (261 mg, 1.5 mmol) were added to a pressure tube equipped with a magnetic pole, replaced with argon, and placed at 120°C for 24 hours. After the reaction was completed, it was quenched with water (10 mL) and extracted with ethyl acetate (10 mL x 3). The separated organic layer was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 30:1) to obtain 120 mg of 1-(4-bromophenyl)-2-methyl-3-phenylpropan-1-one (III-3ia) product, with a yield of 79%.

[0070] Structural characterization of 1-(4-bromophenyl)-2-methyl-3-phenylpropan-1-one (III-3ia): Colorless oil; 79%, 1 H NMR(400MHz, CDCl3)δ7.92(d,J=7.6Hz,2H),7.56–7.52(m,1H),7.46–7.42(m,2H),7.28–7.24(m,2H),7.21–7.1 6(m,2H),3.79–3.70(m,1H),3.17(dd,J=14.0,6.4Hz,1H),2.69(dd,J=14.0,8.0Hz,1H),1.20(d,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ203.7,140.0,136.5,132.9,129.1,128.6,128.4,128.3,126.2,42.8,39.4,17.4ppm; HRMS (ESI) calculated for C 16 H 16 BrO[M+H] + :303.0306,found:303.0302.

[0071] Embodiment 10:

[0072]

[0073] Under the protection of argon atmosphere, 1-p-trifluoromethylphenylethanol (95 mg, 0.5 mmol), benzyl alcohol (216 mg, 2.0 mmol), methanol (162 mg, 1.5 mmol), cyclopentadienone iron catalyst (5.3 mg, 2.0 mol%) and potassium phosphate (261 mg, 1.5 mmol) were added to a pressure tube equipped with a magnetic pole, replaced with argon, and placed at 120°C for 24 h. After the reaction was completed, it was quenched with water (10 mL) and extracted with ethyl acetate (10 mL x 3). The separated organic layer was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 30:1) to obtain 80 mg of 2-methyl-3-phenyl-1-(4-(trifluoromethyl)phenyl)propan-1-one (III-3ja) product, with a yield of 55%.

[0074] Structural characterization of 2-methyl-3-phenyl-1-(4-(trifluoromethyl)phenyl)propan-1-one (III-3ja): Colorless oil; 55% yield, 1 H NMR (400MHz, CDCl3) δ7.92–7.90(m,2H),7.58–7.50(m,3H),7.47–7.43(m,2H),7.31(d,J=8.0Hz,2 H),3.81–3.72(m,1H),3.23(dd,J=14.0,7.0Hz,1H),2.78(dd,J=13.6,7.2Hz,1H),1.23(d,J=6.8H z,3H); 13 C NMR (100MHz, CDCl3) δ203.1, 144.1, 136.1, 133.1, 129.4, 128.6 (d, J = 30Hz), 128.2, 125.3(d,J=3.7Hz), 125.27(d,J=3.8Hz), 124.3(d,J=270Hz), 42.5, 38.9, 17.7ppm; 19 F NMR(376MHz,CDCl3)δ-62.3,HRMS(ESI)calculated for C 17 H 16 F3O[M+H] + :293.1075,found:293.1079.

[0075] Embodiment 11:

[0076]

[0077] Under the protection of argon atmosphere, 1-o-fluorophenylethanol (70 mg, 0.5 mmol), benzyl alcohol (216 mg, 2.0 mmol), methanol (162 mg, 1.5 mmol), cyclopentadienone iron catalyst (5.3 mg, 2.0 mol%) and potassium phosphate (261 mg, 1.5 mmol) were added to a pressure tube equipped with a magnetic pole, replaced with argon, and placed at 120°C for 24 hours. After the reaction, it was quenched with water (10 mL) and extracted with ethyl acetate (10 mL x 3). The separated organic layer was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 30:1) to obtain 46 mg of 1-(2-fluorophenyl)-2-methyl-3-phenylpropan-1-one (III-3ka) product, with a yield of 38%.

[0078] Structural characterization of 1-(2-fluorophenyl)-2-methyl-3-phenylpropan-1-one (III-3ka): Colorless oil; 38% yield, 1 H NMR (400MHz, CDCl3) δ7.84–7.82(m,2H),7.50–7.45(m,2H),7.39–7.35(m,2H),7.09–7.05(m,2H),6.88–6.84 (m,2H),3.69–3.60(m,1H),3.06(dd,J=14.0,6.8Hz,1H),2.61(dd,J=14.0,7.4Hz,1H),1.13(d,J=6.8Hz,3H); 13 C NMR (100MHz, CDCl3) δ203.7, 136.5, 135.7, 134.4 (d, J = 253Hz), 130.6 (d, J = 7.7Hz), 128.8, 128.4, 115.2 (d, J = 21Hz), 43.0, 38.6, 17.7ppm; 19 F NMR(376MHz, CDCl3)δ-118.0; HRMS(ESI)calculated for C 16 H 16 FO[M+H] + :243.1107,found:242.1109.

[0079] Embodiment 12:

[0080]

[0081] Under the protection of argon atmosphere, 1-cyclopropylethanol (43 mg, 0.5 mmol), benzyl alcohol (216 mg, 2.0 mmol), methanol (162 mg, 1.5 mmol), cyclopentadienone iron catalyst (5.3 mg, 2.0 mol%) and potassium phosphate (261 mg, 1.5 mmol) were added to a pressure tube equipped with a magnetic pole, replaced with argon, and placed at 120°C for 24 h. After the reaction was completed, it was quenched with water (10 mL) and extracted with ethyl acetate (10 mL x 3). The separated organic layer was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 30:1) to obtain 52 mg of 1-cyclopropyl-2-methyl-3-phenylpropan-1-one (III-3la) product, with a yield of 55%.

[0082] Structural characterization of 1-cyclopropyl-2-methyl-3-phenylpropan-1-one (III-3la): Colorless oil; 55% yield, 1 H NMR (400MHz, CDCl3) δ7.32–7.29(m,2H),7.24–7.19(m,3H),3.11–3.10(m,1H),3.04–2.96(m,1H),2.62( dd,J=13.6,7.6Hz,1H),1.97–1.91(m,1H),1.16(d,J=6.8Hz,3H),1.01–0.97(m,1H),0.88–0.81(m,1H); 13 C NMR(100MHz, CDCl3)δ213.9,139.9,129.1,128.3,126.2,49.0,39.0,19.7,16.3,11.0,10.9ppm; HRMS(ESI)calculated for C 13 H 17 O[M+H] + :189.1201,found:189.1203.

[0083] Embodiment 13:

[0084]

[0085] Under the protection of argon atmosphere, 1-phenylethanol (61 mg, 0.5 mmol), p-methylbenzyl alcohol (245 mg, 2.0 mmol), methanol (162 mg, 1.5 mmol), cyclopentadienone iron catalyst (5.3 mg, 2.0 mol%) and potassium phosphate (261 mg, 1.5 mmol) were added to a pressure tube equipped with a magnetic pole, replaced with argon, and placed at 120°C for 24 hours. After the reaction was completed, it was quenched with water (10 mL) and extracted with ethyl acetate (10 mL x 3). The separated organic layer was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 30:1) to obtain 98 mg of 2-methyl-1-phenyl-3-(p-tolyl)propan-1-one (III-3ab) product, with a yield of 82%.

[0086] Structural characterization of 2-methyl-1-phenyl-3-(p-tolyl)propan-1-one (III-3ab): Colorless oil; 82% yield, 1 H NMR (400MHz, CDCl3) δ7.95–7.92(m,2H),7.57–7.53(m,1H),7.47–7.43(m,2H),7.11–7.06(m,4H),3.77–3. 68(m,1H),3.13(dd,J=13.6,6.0Hz,1H),2.65(dd,J=13.6,8.0Hz,1H),2.30(s,3H),1.19(d,J=8.0Hz,3H); 13 C NMR(100MHz, CDCl3)δ203.9,136.8,136.5,135.7,133.0,129.1,129.0,128.6,128.3,42.8,38.9,21.0,17.3ppm; HRMS(ESI)calculated for C 17 H 19 O[M+H] + :239.1358,found:239.1356.

[0087] Embodiment 14:

[0088]

[0089] Under the protection of argon atmosphere, 1-phenylethanol (61 mg, 0.5 mmol), p-methoxybenzyl alcohol (277 mg, 2.0 mmol), methanol (162 mg, 1.5 mmol), cyclopentadienone iron catalyst (5.3 mg, 2.0 mol%) and potassium phosphate (261 mg, 1.5 mmol) were added to a pressure tube equipped with a magnetic pole, replaced with argon, and placed at 120°C for 24 hours. After the reaction was completed, it was quenched with water (10 mL) and extracted with ethyl acetate (10 mL x 3). The separated organic layer was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 30:1) to obtain 106 mg of 3-(4-methoxyphenyl)-2-methyl-1-phenylpropan-1-one (III-3ac) product, with a yield of 83%.

[0090] Structural characterization of 3-(4-methoxyphenyl)-2-methyl-1-phenylpropan-1-one (III-3ac): Colorless oil; 83% yield, 1 H NMR (400MHz, CDCl3) δ7.92(d,J=7.2Hz,2H),7.56–7.52(m,1H),7.46–7.43(m,1H),7.11(d,J=8.4Hz,2H),6.80(d,J=8.0H z,2H),3.78(s,3H),3.73–3.68(m,1H),3.11(dd,J=13.6,6.2Hz,1H),2.64(dd,J=14.0,6.8Hz,1H),1.19(d,J=6.8Hz,3H); 13 C NMR (100MHz, CDCl3) δ204.0,158.0,136.5,132.9,132.0,130.0,128.6,128.3,113.8,55.2,43.0,38.5,17.3ppm; HRMS (ESI) calculated for C 17 H 19 O[M+H] + :255.1307,found:255.1310.

[0091] Embodiment 15:

[0092]

[0093] Under the protection of argon atmosphere, 1-phenylethanol (61 mg, 0.5 mmol), o-methylbenzyl alcohol (245 mg, 2.0 mmol), methanol (162 mg, 1.5 mmol), cyclopentadienone iron catalyst (5.3 mg, 2.0 mol%) and potassium phosphate (261 mg, 1.5 mmol) were added to a pressure tube equipped with a magnetic pole, replaced with argon, and placed at 120°C for 24 h. After the reaction was completed, it was quenched with water (10 mL) and extracted with ethyl acetate (10 mL x 3). The separated organic layer was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 30:1) to obtain 88 mg of 2-methyl-1-phenyl-3-(o-tolyl)propan-1-one (III-3ad) product, with a yield of 74%.

[0094] Structural characterization of 2-methyl-1-phenyl-3-(o-tolyl)propan-1-one (III-3ad): Colorless oil; 74% yield, 1 H NMR(400MHz, CDCl3)δ7.97(d,J=6.8Hz,2H),7.59–7.56(m,1H),7.50–7.46(m,2H),7.14–7.10(m,4H),3.80– 3.72(m,1H),3.17(dd,J=13.6,6.2Hz,1H),2.68(dd,J=14.0,8.0Hz,1H),2.33(s,3H),1.23(d,J=6.8Hz,3H); 13 C NMR(100MHz, CDCl3)δ203.9,136.8,136.5,135.7,133.0,129.1,129.0,128.7,128.3,42.9,39.0,21.0,17.3ppm; HRMS(ESI)calculated for C 17 H 19 O[M+H] + :239.1358,found:239.1356.

[0095] Embodiment 16:

[0096]

[0097] Under the protection of argon atmosphere, 1-phenylethanol (61 mg, 0.5 mmol), 3,4-dimethylbenzyl alcohol (272 mg, 2.0 mmol), methanol (162 mg, 1.5 mmol), cyclopentadienone iron catalyst (5.3 mg, 2.0 mol%) and potassium phosphate (261 mg, 1.5 mmol) were added to a pressure tube equipped with a magnetic pole, replaced with argon, and placed at 120°C for 24 hours. After the reaction was completed, it was quenched with water (10 mL) and extracted with ethyl acetate (10 mL x 3). The separated organic layer was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 30:1) to obtain 96 mg of 3-(3,4-dimethylphenyl)-2-methyl-1-phenylpropan-1-one (III-3ae) product, with a yield of 76%.

[0098] Structural characterization of 3-(3,4-dimethylphenyl)-2-methyl-1-phenylpropan-1-one (III-3ae): Colorless oil; 76% yield, 1 H NMR (400MHz, CDCl3) δ7.95–7.93(m,2H),7.56–7.53(m,1H),7.47–7.43(m,2H),7.03(d,J=7.6Hz,1H),6.96–6.90(m,2H),3 .76–3.67(m,1H),3.10(dd,J=13.6,5.8Hz,1H),2.61(dd,J=13.6,8.0Hz,1H),2.22(d,J=4.8Hz,6H),1.19(d,J=6.8Hz,3H); 13 C NMR (100MHz, CDCl3) δ203.9,137.3,136.5,134.3,132.9,130.4,130.0,129.6,128.6,128.3,126.4,42.8,38.9,19.8,19.3,17.3ppm; HRMS(ESI) calculated for C 18 H 21 O[M+H] + :253.1314,found:253.1315.

[0099] Embodiment 17:

[0100]

[0101] Under the protection of argon atmosphere, 1-phenylethanol (61 mg, 0.5 mmol), p-bromobenzyl alcohol (373 mg, 2.0 mmol), methanol (162 mg, 1.5 mmol), cyclopentadienone iron catalyst (5.3 mg, 2.0 mol%) and potassium phosphate (261 mg, 1.5 mmol) were added to a pressure tube equipped with a magnetic pole, replaced with argon, and placed at 120°C for 24 hours. After the reaction was completed, it was quenched with water (10 mL) and extracted with ethyl acetate (10 mL x 3). The separated organic layer was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 30:1) to obtain 123 mg of 3-(4-bromophenyl)-2-methyl-1-phenylpropan-1-one (III-3af) product, with a yield of 81%.

[0102] Structural characterization of 3-(4-bromophenyl)-2-methyl-1-phenylpropan-1-one (III-3af): Colorless oil; 81% yield, 1 H NMR (400MHz, CDCl3) δ7.95–7.92(m,2H),7.59–7.56(m,1H),7.49–7.45(m,2H),7.41(d,J=8.0Hz,2H),7.11(d,J= 8.4Hz,2H),3.79–3.70(m,1H),3.15(dd,J=13.6,6.8Hz,1H),2.42(dd,J=13.6,7.6Hz,1H),1.23(d,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ203.4,139.0,136.3,133.1,131.5,130.9,128.7,128.3,120.0,42.6,38.6,17.7ppm; HRMS (ESI) calculated for C 16 H 17 BrO[M+H] + :304.0306,found:304.0309.

[0103] Embodiment 18:

[0104]

[0105] Under the protection of argon atmosphere, 1-phenylethanol (61 mg, 0.5 mmol), p-fluorobenzyl alcohol (253 mg, 2.0 mmol), methanol (162 mg, 1.5 mmol), cyclopentadienone iron catalyst (5.3 mg, 2.0 mol%) and potassium phosphate (261 mg, 1.5 mmol) were added to a pressure tube equipped with a magnetic pole, replaced with argon, and placed at 120°C for 24 hours. After the reaction was completed, it was quenched with water (10 mL) and extracted with ethyl acetate (10 mL x 3). The separated organic layer was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 30:1) to obtain 84 mg of 3-(4-fluorophenyl)-2-methyl-1-phenylpropan-1-one (III-3ag) product, with a yield of 69%.

[0106] Structural characterization of 3-(4-fluorophenyl)-2-methyl-1-phenylpropan-1-one (III-3ag): Colorless oil; 69% yield, 1 H NMR (400MHz, CDCl3) δ7.91–7.88(m,2H),7.56–7.52(m,2H),7.45–7.42(m,2H),7.15–7.12(m,2H),6.95–6.90 (m,2H),3.75–3.66(m,1H),3.12(dd,J=13.6,6.6Hz,1H),2.67(dd,J=13.6,7.4Hz,1H),1.19(d,J=6.8Hz,3H); 13 C NMR (100MHz, CDCl3) δ203.6, 136.4, 134.3 (d, J = 253Hz), 130.5 (d, J = 7.7Hz), 128.7, 128.3, 115.1 (d, J = 21Hz), 42.9, 38.5, 17.6ppm; 19 F NMR(376MHz, CDCl3)δ-117.1; HRMS(ESI)calculated for C 16 H 16 FO[M+H] + :243.1107,found:243.1109.

[0107] Embodiment 19:

[0108]

[0109] Under the protection of argon atmosphere, 1-phenylethanol (61 mg, 0.5 mmol), p-trifluorobenzyl alcohol (352 mg, 2.0 mmol), methanol (162 mg, 1.5 mmol), cyclopentadienone iron catalyst (5.3 mg, 2.0 mol%) and potassium phosphate (261 mg, 1.5 mmol) were added to a pressure tube equipped with a magnetic pole, replaced with argon, and placed at 120°C for 24 h. After the reaction was completed, it was quenched with water (10 mL) and extracted with ethyl acetate (10 mL x 3). The separated organic layer was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 30:1) to obtain 103 mg of 3-(4-trifluorophenyl)-2-methyl-1-phenylpropan-1-one (III-3ah) product, with a yield of 70%.

[0110] Structural characterization of 3-(4-trifluorophenyl)-2-methyl-1-phenylpropan-1-one (III-3ah): Colorless oil; 70% yield, 1 H NMR (400MHz, CDCl3) δ7.91(d,J=7.2Hz,2H),7.57–7.54(m,1H),7.51(d,J=8.0Hz,2H),7.47–7.43(m,2H),7.31(d,J =8.0Hz,2H),3.81–3.72(m,1H),3.23(dd,J=13.6,6.8Hz,1H),2.78(dd,J=13.6,7.4Hz,1H),1.23(d,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ203.1, 144.1, 136.2, 133.2, 129.4, 128.6 (d, J = 30Hz), 128.3, 125.3(d,J=3.7Hz), 125.27(d,J=3.8Hz), 124.3(d,J=270Hz), 42.5, 40.0, 17.8ppm; 19 F NMR(376MHz, CDCl3)δ-62.4; HRMS(ESI)calculated for C 17 H 16 F3O[M+H] + :293.1075,found:293.1079.

[0111] Embodiment 20:

[0112]

[0113] Under the protection of argon atmosphere, 1-phenylethanol (61 mg, 0.5 mmol), furan-2-ylmethanol (197 mg, 2.0 mmol), methanol (162 mg, 1.5 mmol), cyclopentadienone iron catalyst (5.3 mg, 2.0 mol%) and potassium phosphate (261 mg, 1.5 mmol) were added to a pressure tube equipped with a magnetic pole, replaced with argon, and placed at 120°C for 24 h. After the reaction was completed, it was quenched with water (10 mL) and extracted with ethyl acetate (10 mL x 3). The separated organic layer was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 30:1) to obtain 81 mg of 3-(furan-2-yl)-2-methyl-1-phenylpropan-1-one (III-3ai) product, with a yield of 75%.

[0114] Structural characterization of 3-(furan-2-yl)-2-methyl-1-phenylpropan-1-one (III-3ai): Colorless oil; 75% yield, 1 H NMR (400MHz, CDCl3) δ7.95(d,J=7.6Hz,2H),7.57–7.54(m,1H),7.48–7.44(m,2H),7.285(s,1H),6.24(d,J=2.4Hz,1H),6. 01(d,J=3.2Hz,1H),3.91–3.82(m,1H),3.15(dd,J=14.8,6.4Hz,1H),2.76(dd,J=15.2,7.6Hz,1H),1.22(d,J=6.8Hz,3H); 13 CNMR(100MHz, CDCl3)δ203.3,153.7,141.2,136.2,133.0,128.7,128.4,110.2,106.5,40.0,31.6,17.5ppm; HRMS(ESI)calculated for C 14 H 15 O2[M+H] + :215.0994,found:215.0996.

[0115] Embodiment 21:

[0116]

[0117] Under the protection of argon atmosphere, 1-phenylethanol (61 mg, 0.5 mmol), thiophene-2-ylmethanol (229 mg, 2.0 mmol), methanol (162 mg, 1.5 mmol), cyclopentadienone iron catalyst (5.3 mg, 2.0 mol%) and potassium phosphate (261 mg, 1.5 mmol) were added to a pressure tube equipped with a magnetic pole, replaced with argon, and placed at 120°C for 24 hours. After the reaction was completed, it was quenched with water (10 mL) and extracted with ethyl acetate (10 mL x 3). The separated organic layer was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 30:1) to obtain 72 mg of 2-methyl-1-phenyl-3-(thiophene-2-yl)propan-1-one (III-3aj) product, with a yield of 62%.

[0118] Structural characterization of 2-methyl-1-phenyl-3-(thiophen-2-yl)propan-1-one (III-3aj): Colorless oil; 62% yield, 1 H NMR (400MHz, CDCl3) δ7.96–7.95(m,2H),7.58–7.54(m,1H),7.48–7.44(m,2H),7.11–7.10(m,1H),6.89–6.87(m,1H),6 .81–6.80(m,1H),3.80–3.75(m,1H),3.38(dd,J=14.8,7.0Hz,1H),2.95(dd,J=14.8,7.2Hz,1H),1.26(d,J=6.8Hz,3H); 13 C NMR (100MHz, CDCl3) δ203.3,142.4,136.3,133.1,128.7,128.3,126.8,125.6,123.6,43.3,33.3,17.8ppm; HRMS (ESI) calculated for C 14 H 15 OS[M+H] + :231.0765,found:231.0763.

[0119] Embodiment 22:

[0120]

[0121] Under the protection of argon atmosphere, 1-p-methoxyphenylethanol (76 mg, 0.5 mmol), thiophene-2-ylmethanol (229 mg, 2.0 mmol), methanol (162 mg, 1.5 mmol), cyclopentadienone iron catalyst (5.3 mg, 2.0 mol%) and potassium phosphate (261 mg, 1.5 mmol) were added to a pressure tube equipped with a magnetic pole, replaced with argon, and placed at 120°C for 24 hours. After the reaction was completed, it was quenched with water (10 mL) and extracted with ethyl acetate (10 mL x 3). The separated organic layer was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 30:1) to obtain 99 mg of 1-(4-methoxyphenyl)-2-methyl-3-(thiophene-2-yl)propan-1-one (III-3cj) product, with a yield of 76%.

[0122] Structural characterization of 1-(4-methoxyphenyl)-2-methyl-3-(thiophen-2-yl)propan-1-one (III-3cj): Colorless oil; 76% yield, 1 H NMR (400MHz, CDCl3) δ7.98–7.96(m,2H),7.31–7.28(m,1H),6.97–6.95(m,2H),6.27–6.25(m,1H),6.03(d,J=3.2Hz,1 H),3.89(s,3H),3.87–3.81(m,1H),3.15(dd,J=14.8,6.4Hz,1H),2.77(dd,J=15.2,7.6Hz,1H),1.23(d,J=6.8Hz,3H); 13 C NMR(100MHz, CDCl3)δ201.8,163.5,153.9,141.2,130.6,129.1,113.8,110.2,106.4,55.5,39.6,31.8,17.7ppm; HRMS(ESI)calculated for C 15 H 17 O2S[M+H] + :261.0871,found:261.0872.

[0123] The preferred embodiments of the present invention disclosed above are only used to help illustrate the present invention. The preferred embodiments do not describe all the details in detail, nor do they limit the invention to the specific implementation methods described. Obviously, many modifications and changes can be made according to the content of this specification. This specification selects and specifically describes these embodiments in order to better explain the principles and practical applications of the present invention, so that those skilled in the art can understand and use the present invention well. The present invention is limited only by the claims and their full scope and equivalents.

Claims

1. A method for preparing an α-alkyl ketone derivative, characterized in that: The reaction formula is as follows, comprising the following steps: under the protection of inert gas, using cyclopentadienone iron as shown in formula (VI) as a catalyst, placing a mixture of 1-substituted ethanol as shown in formula (I), an aromatic primary alcohol as shown in formula (II), methanol and a base, stirring and reacting at 100-140° C. for 12-36 hours to obtain an α-alkyl ketone derivative as shown in (III); Wherein, in formula (I), R is phenyl, substituted phenyl, naphthyl or cyclopropyl, and the substituent in the substituted phenyl is alkyl, alkoxy, halogen or haloalkyl; in formula (II), R 1 It is phenyl, substituted phenyl or heterocyclic aryl, and the substituent in the substituted phenyl is alkyl, alkoxy, halogen or halogenated alkyl.

2. The method for preparing an α-alkyl ketone derivative according to claim 1, characterized in that: The method also includes adding water to quench the reaction after the reaction is completed, extracting with an organic solvent, concentrating the separated organic solvent layer under reduced pressure, and then separating by column chromatography to obtain an α-alkyl ketone derivative as shown in (III).

3. The method for preparing an α-alkyl ketone derivative according to claim 2, characterized in that: The organic solvent used for the extraction is ethyl acetate or dichloromethane.

4. The method for preparing α-alkyl ketone derivatives according to claim 2, characterized in that: The solvent used for column chromatography separation is petroleum ether / ethyl acetate, and the volume ratio thereof is 10:1 to 50:

1.

5. The method for preparing α-alkyl ketone derivatives according to claim 1, characterized in that: The molar ratio of the 1-substituted ethanol shown in formula (I), methanol, the primary aromatic alcohol shown in formula (II), the base and the cyclopentadienone iron shown in formula (VI) is 1:1.5-10:1.5-5:1-5:0.02-0.

1.

6. The method for preparing α-alkyl ketone derivatives according to claim 5, characterized in that: The molar ratio of the 1-substituted ethanol shown in formula (I), methanol, the primary aromatic alcohol shown in formula (II), the base and the cyclopentadienone iron shown in formula (VI) is 1:3:4:3:0.

02.

7. The method for preparing α-alkyl ketone derivatives according to claim 1, characterized in that: The base is one or more of potassium phosphate, potassium carbonate, potassium tert-butoxide or cesium carbonate.

8. The method for preparing α-alkyl ketone derivatives according to claim 7, characterized in that: The alkali is potassium phosphate.

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