Preparation method of aromatic carbonyl compound

Abstract

The invention discloses a preparation method of an aromatic carbonyl compound and relates to the field of preparation of related products in pharmacy, agriculture and the like. The preparation method comprises the following steps: by taking aryl methyl halide as a raw material, adding tetraphenylphosphonium bromide, calcium fluoride and ethylenediaminetetraacetic acid into N, N-dimethylformamide, and rapidly obtaining a target product with high yield at the temperature of 40-60 DEG C. According to the aromatic carbonyl compound, the preparation method is simple, the yield is excellent, and a new thought is provided for preparing aromatic aldehyde ketone from benzyl halide.

Description

Technical Field

[0001] It relates to a method for directly preparing aromatic carbonyl compounds from aromatic methyl halides and belongs to the field of organic synthesis methodology. Background Art

[0002] The oxidation reaction of the benzylic C-X bond specifically refers to the reaction type in which a compound containing a C-X bond directly connected to an aromatic ring undergoes an oxidation process and is then converted into corresponding aromatic alcohols, aldehydes, carboxylic acids and other compounds. The reaction products are key raw materials and intermediates in organic synthesis and have extensive applications in many fields such as medicine, pesticides, spices, dyes and petrochemical industry. At present, there are relatively few methods for oxidizing benzylic halogen compounds, and most of them require precious metals, oxidants with complex preparation processes or high costs, and microwave catalysis. When using 4-hydroxypyridine nitrate-functionalized silica gel as the oxidant as reported in the literature (DOI: 10.1080 / 00304948.2021.1880838), sodium hydroxide as the catalyst, and water as the solvent, reacting at 20 °C for 0.5 h under microwave irradiation, the yield of the product (II) similar to that of the present invention reaches 99%; when using 4-nitrosotoluene as the oxidant as reported in the literature (DOI: 10.1021 / acs.orglett.1c02272), sodium acetate as the catalyst, and hexafluoroisopropanol and dichloromethane as the solvents, reacting at 60 °C for 6 h, the yield of the product (II) similar to that of the present invention reaches 72%; when using bismuth(III) nitrate pentahydrate as the oxidant as reported in the literature (DOI: 10.1007 / s11696-018-0657-6), tetrabutylammonium fluoride as the solvent and catalyst, reacting at 100 °C for 1 h, the yield of the product (II) similar to that of the present invention reaches 91%. At present, there is still a lack of reports on a method for directly preparing aromatic carbonyl compounds from aromatic methyl halides in a green and rapid manner without precious metals and complex oxidants. Summary of the Invention

[0003] In the present invention, an aromatic methyl halide is directly reacted with tetraphenylphosphonium bromide, calcium fluoride, and ethylenediaminetetraacetic acid under heating conditions to obtain a product of aromatic carbonyl compounds in high yield.

[0004] The structure of the aromatic carbonyl compounds prepared in the present invention is:

[0005]

[0006] Wherein, R 1 is selected from 4-H, 4-F, 4-Br, 4-CN, 4-Cl, 4-NO 2 ; R 2 is selected from H, Me, -Ph, 4-ClPh, benzoyl, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl.

[0007] Further, the compound shown in Formula I is selected from any one of the structures shown in the following Formulas II to VI.

[0008]

[0009] Further, in II, R = 4-H, 4-F, 4-Br, 4-CN, 4-Cl, 4-NO 2 . In III, R = 4-F, 4-H, 4-Cl. In IV, R = 4-F, 4-Br, 4-OMe. In V, R = Me, Et, iPr. In VI, R = 4-H, 4-Cl.

[0010] Further, the compound I is prepared from the compound VII arylmethyl halide as a raw material.

[0011]

[0012] Further, the preparation method of the compound I is as follows: at 40 - 60 °C and under normal pressure, the arylmethyl halide, tetraphenylphosphonium bromide, ethylenediaminetetraacetic acid, and calcium fluoride are successively added to DMF and reacted for 3 - 5 h. After the reaction is completed, it is gradually restored to room temperature, and a small amount of saturated sodium bicarbonate aqueous solution is added to quench the reaction. It is extracted with ethyl acetate and saturated brine, and the organic phase is concentrated, and the yield is 75 - 99%.

[0013] Compared with the prior art, the present invention has the following beneficial effects:

[0014] 1) The present invention for the first time prepares a variety of aromatic carbonyl compounds with tetraphenylphosphonium bromide / ethylenediaminetetraacetic acid / calcium fluoride as an oxidation system;

[0015] 2) The preparation method of the present invention is simple, the reaction time is short, the reaction conditions are mild, and the post-treatment is simple;

[0016] 3) The present invention has wide applicability, low raw material prices, high yields, and excellent practical value. Specific Embodiments

[0017] The technical solution of the present invention is not limited to the specific embodiments listed below, and also includes any combination between the specific embodiments.

[0018] Specific Embodiment 1: The structure of the aromatic carbonyl substance in this embodiment is:

[0019]

[0020] Among them, R 1 is selected from 4-H, 4-F, 4-Br, 4-CN, 4-Cl, 4-NO 2 ; R 2Selected from H, Me, -Ph, 4-ClPh, benzoyl, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl.

[0021] Embodiment 2: The compound prepared in this embodiment is selected from any one of the structures shown in the following Formulas II to VI,

[0022]

[0023] wherein in II, R = 4-H, 4-F, 4-Br, 4-CN, 4-Cl, 4-NO 2 . In III, R = 4-F, 4-H, 4-Cl. In IV, R = 4-F, 4-Br, 4-H. In V, R = Me, Et, iPr. In VI, R = 4-H, 4-Cl.

[0024] Embodiment 3: The preparation method of the aromatic aldehyde II prepared in this embodiment is as follows: At 40 °C and under normal pressure, arylmethyl bromide, tetraphenylphosphonium bromide, ethylenediaminetetraacetic acid, and calcium fluoride are successively added to DMF and reacted for 3 h. After the reaction is completed, the temperature is gradually restored to room temperature, and a small amount of saturated sodium bicarbonate aqueous solution is added to quench the reaction. It is extracted with ethyl acetate and saturated brine, and the organic phase is concentrated to obtain a colorless oily liquid with a yield of 95-99%.

[0025] Embodiment 4: The preparation method of 1-phenyl-2-aryl ethanedione III prepared in this embodiment is as follows: At 60 °C and under normal pressure, 2-bromo-2-arylacetophenone, tetraphenylphosphonium bromide, ethylenediaminetetraacetic acid, and calcium fluoride are successively added to DMF and reacted for 3 h. After the reaction is completed, the temperature is gradually restored to room temperature, and a small amount of saturated sodium bicarbonate aqueous solution is added to quench the reaction. It is extracted with ethyl acetate and saturated brine, and the organic phase is concentrated and purified by column chromatography with a volume ratio of n-hexane:ethyl acetate = 20:1 to obtain a white crystalline powder with a yield of 90-95%.

[0026] Embodiment 5: The preparation method of the arylacetone IV prepared in this embodiment is as follows: At 60 °C and under normal pressure, 1-bromoaryl ethane, tetraphenylphosphonium bromide, ethylenediaminetetraacetic acid, and calcium fluoride are successively added to DMF and reacted for 3 h. The temperature is gradually restored to room temperature, the reaction is completed, extracted, dried, and purified by column chromatography with a volume ratio of n-hexane:ethyl acetate = 20:1 to obtain a yellow oily liquid with a yield of 91-95%.

[0027] Specific Embodiment Six: The preparation method of 2-oxophenylacetic acid ester V prepared in this embodiment is as follows: At 60 °C and under normal pressure, α-bromophenylacetic acid ester, tetraphenylphosphonium bromide, ethylenediaminetetraacetic acid, and calcium fluoride are successively added to DMF and reacted for 3 h. Then it is gradually cooled to room temperature. After the reaction is completed, extraction and drying are carried out, and column chromatography purification is carried out with a volume ratio of n-hexane:ethyl acetate = 20:1 to obtain a yellow oily liquid with a yield of 75-78%.

[0028] Specific Embodiment Seven: The preparation method of diaryl ketone VI prepared in this embodiment is as follows: At 60 °C and under normal pressure, diaryl bromomethane, tetraphenylphosphonium bromide, ethylenediaminetetraacetic acid, and calcium fluoride are successively added to DMF and reacted for 3 h. Then it is gradually cooled to room temperature. After the reaction is completed, extraction and drying are carried out, and column chromatography purification is carried out with a volume ratio of n-hexane:ethyl acetate = 20:1 to obtain a yellow solid with a yield of 94-97%.

[0029] The following is a detailed description of the embodiments of the present invention. The following embodiments are implemented on the premise of the technical solution of the present invention, and detailed implementation schemes and specific operation processes are given. However, the protection scope of the present invention is not limited to the following embodiments.

[0030] Example 1: The preparation method of benzaldehyde in this example is carried out according to the following steps: At room temperature, 0.1 mmol of benzyl bromide, 0.15 mmol of tetraphenylphosphonium bromide, 0.15 mmol of ethylenediaminetetraacetic acid, and 0.05 mmol of calcium fluoride are added to a 10 mL thick-walled glass tube, and 5 mL of DMF is added. Then it is placed in a water bath, and the reaction temperature is adjusted to 40 °C. The reaction is carried out at normal pressure for 3 h. After the reaction is completed, it is cooled. The reaction is monitored by thin-layer chromatography (n-hexane:ethyl acetate = 20:1). A small amount of saturated sodium bicarbonate aqueous solution is added to quench the reaction. Extraction is carried out with ethyl acetate and saturated brine. After concentrating the organic phase, wet column chromatography is carried out using 300-400 mesh silica gel powder. The mobile phase ratio is n-hexane:ethyl acetate = 20:1 to obtain a colorless oily liquid with a yield of 99%. The structural data of benzaldehyde are as follows: 1 HNMR(300MHz,CDCl3)δ10.03(s,1H),7.91-7.88(m,2H),7.66-7.61(m,1H),7.56-7.52(m,2H). 13 CNMR(75MHz,CDCl 3 )δ192.5,136.4,134.6,129.8,129.1.

[0031] Example 2: The preparation method of p-fluorobenzaldehyde in this example. All experimental conditions and treatment methods are the same as those in Example 1, except that benzyl bromide is changed to p-fluorobenzyl bromide, and the final product yield is 95%. The structural data of p-fluorobenzaldehyde are as follows: 1 HNMR(300MHz,CDCl3 ) δ 9.99 (s, 1H), 7.90–7.93 (m, 2H), 7.19–7.23 (t, 2H). 13 C NMR (75 MHz, CDCl 3 ) δ 190.6, 168.0, 165.4, 133.1, 132.4, 132.3, 116.6, 116.4.

[0032] Example 3: The preparation method of p-bromobenzaldehyde. All experimental conditions and treatment methods are the same as those in Example 1, except that benzyl bromide is replaced with p-bromobenzyl bromide, and the final product yield is 98%. The structural data of p-bromobenzaldehyde are as follows: 1 H NMR (300 MHz, CDCl 3 ) δ 9.91 (s, 1H), 7.68 (d, J = 8.3 Hz, 2H), 7.62 (d, J = 8.3 Hz, 2H). 13 C NMR (75 MHz, CDCl 3 ) δ 191.1, 135.1, 132.4, 131.0, 129.8.

[0033] Example 4: The preparation method of p-cyanobenzaldehyde. All experimental conditions and treatment methods are the same as those in Example 1, except that benzyl bromide is replaced with p-cyanobenzyl bromide, and the final product yield is 96%. The structural data of p-cyanobenzaldehyde are as follows: 1 H NMR (300 MHz, CDCl 3 ) δ 10.11 (s, 1H), 8.06–7.94 (m, 2H), 7.92–7.80 (m, 2H). 13 C NMR (75 MHz, CDCl 3 ) δ 190.6, 138.7, 132.9, 129.9, 117.7, 117.6.

[0034] Example 5: The preparation method of p-chlorobenzaldehyde. All experimental conditions and treatment methods are the same as those in Example 1, except that benzyl bromide is replaced with p-chlorobenzyl bromide, and the final product yield is 97%. The structural data of p-chlorobenzaldehyde are as follows: 1 H NMR (300 MHz, CDCl 3 ) δ 9.92 (s, 1H), 7.76 (d, J = 8.4 Hz, 2H), 7.45 (d, J = 8.3 Hz, 2H). 13 C NMR (75 MHz, CDCl 3 ) δ 190.9, 141.0, 134.7, 130.9, 129.5.

[0035] Example 6: This example is a preparation method of p-nitrobenzaldehyde. All experimental conditions and treatment methods are the same as those in Example 1, except that benzyl bromide is changed to p-nitrobenzyl bromide, and the final product yield is 88%. The structural data of p-nitrobenzaldehyde are as follows: 1 H NMR(300MHz,Chloroform-d)δ10.16(s,1H),8.41-8.39(m,2H),8.09-8.07(m,2H). 13 CNMR(75MHz,Chloroform-d)δ190.4,138.1,135.2,130.6,124.4.

[0036] Example 7: This example is a preparation method of benzil. The steps are as follows: At room temperature, 0.1 mmol of 2-bromo-2-phenylacetophenone, 0.15 mmol of tetraphenylphosphonium bromide, 0.15 mmol of ethylenediaminetetraacetic acid, and 0.05 mmol of calcium fluoride are added to a 10 mL thick-walled glass tube, and 5 mL of DMF is added. Then it is placed in a water bath, the reaction temperature is adjusted to 60 °C, and the reaction is carried out at normal pressure for 5 h. After the reaction is completed, it is cooled, and thin layer chromatography is used to monitor the reaction (n-hexane:ethyl acetate = 20:1). A small amount of saturated sodium bicarbonate aqueous solution is added to quench the reaction, and extraction is carried out with ethyl acetate and saturated brine. After concentrating the organic phase, wet column chromatography is carried out using 300-400 mesh silica gel powder, and the mobile phase ratio is n-hexane:ethyl acetate = 20:1, obtaining a white crystalline powder with a yield of 92%. The structural data of benzil are as follows: 1 H NMR(300MHz,Chloroform-d)δ7.97–7.95(m,4H),7.65–7.60(m,2H),7.50–7.46(m,4H). 13 C NMR(75MHz,Chloroform-d)δ194.6,135.0,132.9,129.9,129.1.

[0037] Example 8: This example is a preparation method of 4-fluorobenzil. All experimental conditions and treatment methods are the same as those in Example 7, except that 2-bromo-2-phenylacetophenone is changed to 2-bromo-2-(p-fluorophenyl)acetophenone, and the final product yield is 93%. The structural data of the product 4-fluorobenzil are as follows: 1 H NMR(300MHz,Chloroform-d)δ8.07–7.98(m,4H),7.72–7.66(m,2H),7.57–7.51(m,2H),7.28–7.17(m,3H). 1313C NMR (75 MHz, Chloroform-d) δ 194.2, 192.9, 166.9, 135.2, 133.0, 132.9, 130.1, 129.6, 129.2, 116.6.

[0038] Example 9: This example is a preparation method of 4-chloroacetophenone. All experimental conditions and treatment methods are the same as those in Example 7, except that 2-bromo-2-phenylacetophenone is replaced with 2-bromo-2-(p-chlorophenyl)acetophenone, and the product yield is 90%. The structural data of the product 4-chloroacetophenone are as follows: 1 1H NMR (300 MHz, Chloroform-d) δ 7.99–7.95 (m, 2H), 7.93 (d, J = 8.4 Hz, 2H), 7.70–7.65 (m, 1H), 7.55–7.52 (m, 2H), 7.50 (d, J = 8.8 Hz, 2H). 13 13C NMR (75 MHz, Chloroform-d) δ 194.1, 193.2, 141.8, 135.2, 132.9, 131.5, 131.4, 130.1, 129.6, 129.2.

[0039] Example 10: This example is a preparation method of acetophenone, which is carried out according to the following steps: At room temperature, 0.1 mmol of 1-bromoethylbenzene, 0.15 mmol of tetraphenylphosphonium bromide, 0.15 mmol of ethylenediaminetetraacetic acid, and 0.05 mmol of calcium fluoride are added to a 10 mL thick-walled glass tube, and 5 mL of DMF is added. Then it is placed in a water bath, the reaction temperature is adjusted to 60 °C, and the reaction is carried out at normal pressure for 3 h. After the reaction is completed, it is cooled, and the reaction is monitored by thin-layer chromatography (n-hexane:ethyl acetate = 20:1). The reaction is quenched with a small amount of saturated sodium bicarbonate aqueous solution, and extracted with ethyl acetate and saturated brine. After concentrating the organic phase, it is wet-columned with 300 - 400 mesh silica gel powder, and the mobile phase ratio is n-hexane:ethyl acetate = 20:1, obtaining a yellow oily liquid with a yield of 92%. The structural data of the product acetophenone are as follows: 1 1H NMR (300 MHz, Chloroform-d) δ 7.98–7.78 (m, 2H), 7.53–7.45 (m, 1H), 7.39 (dd, 2H), 2.54 (s, 3H). 13 13C NMR (75 MHz, Chloroform-d) δ 198.2, 137.1, 133.1, 128.5, 128.3, 26.6.

[0040] Example 11: This example is about the preparation method of fluoroacetophenone. All experimental conditions and treatment methods are the same as those in Example 10, except that 1-bromoethylbenzene is changed to (1-bromoethyl)-4-fluorobenzene, and the product yield is 90%. The structural data of the product fluoroacetophenone are as follows: 1 H NMR(300MHz,Chloroform-d)δ7.97–7.81(m,2H),7.06(t,2H),2.52(s,3H). 13 C NMR(75MHz,Chloroform-d)δ196.5,167.0,164.5,133.6,133.5,131.0,130.9,115.7,115.5,26.5.

[0041] Example 12: This example is about the preparation method of bromoacetophenone. All experimental conditions and treatment methods are the same as those in Example 10, except that 2-bromoethylbenzene is changed to 1-(1-bromoethyl)-4-bromobenzene, and the product yield is 95%. The structural data of the product bromoacetophenone are as follows: 1 H NMR(300MHz,Chloroform-d)δ7.87–7.77(m,2H),7.65–7.56(m,2H),2.59(s,3H). 13 C NMR(75MHz,Chloroform-d)δ197.0,135.7,131.8,129.8,128.3,26.5.

[0042] Example 13: This example is about the preparation method of ethyl 2-oxophenylacetate. The specific steps are as follows: At room temperature, 0.1 mmol of ethyl α-bromophenylacetate, 0.15 mmol of tetraphenylphosphonium bromide, 0.15 mmol of ethylenediaminetetraacetic acid, and 0.05 mmol of calcium fluoride are added to a 10 mL thick-walled glass tube, and 5 mL of DMF is added. Then it is placed in a water bath, and the reaction temperature is adjusted to 60 °C. The reaction is carried out at atmospheric pressure for 5 h. After the reaction is completed, it is cooled, and thin-layer chromatography is used to monitor the reaction (n-hexane:ethyl acetate = 20:1). A small amount of saturated sodium bicarbonate aqueous solution is added to quench the reaction, and it is extracted with ethyl acetate and saturated brine. After concentrating the organic phase, it is wet-columned with 300 - 400 mesh silica gel powder, and the mobile phase ratio is n-hexane:ethyl acetate = 20:1, obtaining a yellow oily liquid with a yield of 75%. The structural data of the product ethyl 2-oxophenylacetate are as follows: 1 H NMR(300MHz,Chloroform-d)δ8.07–7.95(m,2H),7.66(t,1H),7.51(t,2H),4.45(q,2H),1.42(t,3H). 1313C NMR (75 MHz, Chloroform-d) δ 186.5, 163.9, 135.0, 130.0, 128.9, 62.4, 14.1.

[0043] Example 14: This example is a preparation method of methyl 2-oxophenylacetate. All experimental conditions and treatment methods are the same as those in Example 13, except that ethyl α-bromophenylacetate is replaced with methyl α-bromophenylacetate, and the yield is 78%. The structural data of the product methyl 2-oxophenylacetate are as follows: 1 1H NMR (300 MHz, Chloroform-d) δ 8.01–7.98 (m, 2H), 7.66–7.62 (m, 1H), 7.51–7.47 (m, 2H), 3.95 (t, 3H). 13 13C NMR (75 MHz, Chloroform-d) δ 186.2, 164.1, 135.1, 132.5, 130.2, 129.0 52.8.

[0044] Example 15: This example is a preparation method of isopropyl 2-oxophenylacetate. All experimental conditions and treatment methods are the same as those in Example 13, except that ethyl α-bromophenylacetate is replaced with isopropyl α-bromophenylacetate, and the yield is 75%. The structural data of the product isopropyl 2-oxophenylacetate are as follows: 1 1H NMR (300 MHz, Chloroform-d) δ 8.03–7.97 (m, 2H), 7.69–7.62 (m, 1H), 7.51 (t, 2H), 5.33 (m, 1H), 1.42 (s, 3H), 1.41 (s, 3H). 13 13C NMR (75 MHz, Chloroform-d) δ 186.7, 163.6, 134.8, 132.6, 130.0, 128.9, 70.7, 21.7.

[0045] Example 16: This example is a preparation method of benzophenone. The specific steps are as follows: At room temperature, 0.1 mmol of diphenylbromomethane, 0.15 mmol of tetraphenylphosphonium bromide, 0.15 mmol of ethylenediaminetetraacetic acid, and 0.05 mmol of calcium fluoride were added to a 10 mL thick-walled glass tube, and 5 mL of DMF was added. Then it was placed in a water bath, and the reaction temperature was adjusted to 60 °C. The reaction was carried out at atmospheric pressure for 3 h. After the reaction was completed, it was cooled. The reaction was monitored by thin-layer chromatography (n-hexane:ethyl acetate = 20:1). The reaction was quenched with a small amount of saturated sodium bicarbonate aqueous solution, and extracted with ethyl acetate and saturated brine. After concentrating the organic phase, it was wet-columned with 300 - 400 mesh silica gel powder. The mobile phase ratio was n-hexane:ethyl acetate = 20:1, and a white solid was obtained with a yield of 97%. The structural data of the product benzophenone are as follows: 11H NMR (300 MHz, Chloroform-d) δ 7.88–7.71 (m, 4H), 7.64–7.55 (m, 2H), 7.53–7.42 (m, 4H). 13 13C NMR (75 MHz, Chloroform-d) δ 196.8, 137.5, 132.4, 130.1, 128.3.

[0046] Example 17: This example is a preparation method of 4,4'-dichlorobenzophenone. All experimental conditions and treatment methods are the same as those in Example 13, except that diphenylbromomethane is replaced by 4,4'-dichlorodiphenylbromomethane, and the yield is 94%. The structural data of the product 4,4'-dichlorobenzophenone are as follows: 1 1H NMR (300 MHz, Chloroform-d) δ 7.74–7.71 (m, 4H), 7.48–7.46 (m, 4H). 13 13C NMR (75 MHz, Chloroform-d) δ 195.5, 138.9, 135.8, 131.4, 128.4.

Claims

1. The present invention relates to a method for preparing an aromatic carbonyl compound, characterized in that The method comprises the following steps: mixing aryl methyl halide with tetraphenylphosphine bromide, calcium fluoride and ethylenediaminetetraacetic acid, and then placing the mixture in N,N-dimethylformamide at a certain temperature to obtain an aromatic carbonyl compound with a yield of 75-99%. The aromatic carbonyl compound has the structural formula: Wherein, R1 is selected from 4-H, 4-F, 4-Br, 4-CN, 4-Cl, 4-NO2; R2 is selected from H, Me, -Ph, 4-ClPh, benzoyl, methoxycarbonyl, ethoxycarbonyl, isopropyloxycarbonyl.

2. The method for preparing an aromatic carbonyl compound according to claim 1, wherein the reaction temperature is 40-60°C.

3. The method for preparing an aromatic carbonyl compound according to claim 1, wherein the reaction time is 3-5 hours.

4. The method for preparing an aromatic carbonyl compound according to claim 1, wherein the molar ratio of tetraphenylphosphonium bromide to aromatic methyl halide is 1.5:

1.

5. The method for preparing an aromatic carbonyl compound according to claim 1, wherein the molar ratio of calcium fluoride to aromatic methyl halide is 1:

20.

6. The method for preparing an aromatic carbonyl compound according to claim 1, wherein the molar ratio of ethylenediaminetetraacetic acid to aromatic methyl halide is 1.5:1.

Images