Preparation method of light-induced PIFA-participated 2-hydroxybenzil compound
Through the method of light-induced PIFA participation, the problems of many reaction routes, high cost, low yield and poor substrate applicability in the existing 2-hydroxybenzoyl compound synthesis methods are solved, and efficient synthesis under mild conditions is achieved, providing a green and economical synthesis pathway.
Patent Information
- Application Number
- CN202510250505.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-03-04
- Publication Date
- 2025-04-25
AI Technical Summary
The existing synthesis methods of 2-hydroxybenzoyl compounds have problems such as many reaction routes, high cost, low yield and poor substrate applicability.
By using the method of photo-induced PIFA participation, 2-hydroxybenzene compounds were obtained by reacting [bis(trifluoroacetoxy)iodine]benzene and benzoyl in acetonitrile, the reaction conditions were controlled to be mild light and stirring, and the reaction time was 6-24 hours. The solvent was then removed by rotary evaporation and separated by column chromatography.
A green synthesis method with mild conditions, easy operation, cheap and easy to obtain raw materials, high yields and wide application of substrates is achieved, and convenient means to build organic compounds with potential biological activity or pharmacological effects.
Smart Images
Figure BDA0005296814500000021 
Figure BDA0005296814500000022 
Figure BDA0005296814500000031
Abstract
Description
Technical Field
[0001] The invention belongs to the field of organic synthesis, relates to the preparation of 2-hydroxybenzil compounds, and specifically relates to a method for preparing 2-hydroxybenzil compounds with the participation of light-induced PIFA. Background Art
[0002] Benzil derivatives 2-hydroxyphenyl 1,2-diketone (HPDs) are widely present in nature. These compounds not only have a specific structural skeleton, but also exhibit a variety of important biological activities. Such as anti-cancer, antibacterial, anti-aging, bactericidal and anti-hyperemia. In addition, these compounds have been found to have a good inhibitory effect on the activity of carboxyl ester enzymes in the body. Therefore, the exploration of novel and practical synthesis methods of 2-hydroxyphenyl 1,2-diketone compounds has attracted the attention of chemists. In recent years, the reaction strategy of synthesizing 2-hydroxybenzil compounds using simple methods has become a research hotspot in the field of synthetic chemistry. At present, although some synthesis methods of 2-hydroxybenzil compounds have been reported, these strategies focus on the use of transition metal / ligand catalytic systems to cross-couple phenolic compounds and α-hydroxyacetophenone. This type of reaction often requires more reaction routes to prepare substrates, with high reaction costs and low economic benefits. In addition, there are also problems such as poor applicability of reaction substrates and low yields. Summary of the invention
[0003] In view of the above technical problems, the present invention proposes a method for preparing 2-hydroxybenzil compounds with the participation of light-induced PIFA. The method has mild reaction conditions, simple and safe operation, and cheap and readily available raw materials. It is an environmentally friendly green synthesis method and provides a convenient means for constructing organic compounds with potential biological activity or pharmacological effects. The steps are as follows: under light conditions, [bis(trifluoroacetoxy)iodo]benzene and benzil are dissolved in acetonitrile for reaction, the molar ratio of [bis(trifluoroacetoxy)iodo]benzene to benzil is 2-4:1, the reaction time is 6-24h, after the reaction is completed, the solvent is removed by rotary evaporation, and 2-hydroxybenzil compounds are obtained by column chromatography separation.
[0004] The structural formula of the 2-hydroxybenzil is Where R 1 is one of methyl, phenyl, fluorine, chlorine, bromine, nitro, and methoxy; R 2 It is one of methyl, ethyl, methoxy, fluorine, chlorine, bromine, nitro, nitrile, trifluoromethyl, trifluoromethoxy, phenyl, benzyl and dimethylamino.
[0005] The benzil structural formula is Where R 1 It is one of methyl, phenyl, fluorine, chlorine, bromine, nitro and methoxy.
[0006] The general reaction formula of the preparation method is as follows:
[0007]
[0008] The reagents for column chromatography are petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 1: (10-100).
[0009] The present invention has the following beneficial effects: under light conditions, the present invention uses [bis(trifluoroacetyloxy)iodo]benzene (PIFA) as a hydroxylation agent to achieve a one-step hydroxylation reaction of a benzil compound to prepare 2-hydroxyphenyl 1,2-diketone (HPDs). The preparation method of 2-hydroxybenzil compounds with the participation of light-induced PIFA provided by the present invention has the characteristics of mild conditions (light irradiation and stirring reaction), cheap and readily available raw materials, simple operation, high yield, and wide substrate applicability. DETAILED DESCRIPTION
[0010] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.
[0011] Example 1
[0012] The preparation method of the 1-(2-hydroxyphenyl)-2-phenylethane-1,2-dione compound in this embodiment with the participation of light-induced PIFA comprises the following steps:
[0013] In a 10 mL reaction tube, 0.2 mmol of 1,2-diphenylethanedione was dissolved in 2 mL of acetonitrile, and then 0.4 mmol of [bis(trifluoroacetoxy)iodo]benzene (PIFA) was added. The mixture was stirred under light for 12 hours. After the reaction was completed, the solvent was removed by rotary evaporation. The crude product was separated by silica gel column chromatography (petroleum ether: ethyl acetate = 1:10) to obtain the target product.
[0014] The target product structure and identification results are shown below:
[0015]
[0016] White solid (38.9mg, 86%); 1H NMR (400MHz, CDCl3) δ11.36 (s, 1H), 7.95 (d, J = 7.4Hz, 2H), 7.65 (t, J = 7.4Hz, 1H), 7.57-7.40 (m, 4H), 7.05 (d, J = 8.5Hz, 1H), 6.86 (t, J = 7.5Hz, 1H); 13 CNMR (100MHz, CDCl3) δ199.4,192.1,163.4,138.2,135.2,132.7,132.4,130.1,129.2,119.8,118.7,116.9.
[0017] Example 2
[0018] The preparation method of the 1-(2-hydroxy-4-methylphenyl)-2-(p-methyl)ethane-1,2-dione compound in this embodiment with the participation of light-induced PIFA comprises the following steps:
[0019] In a 10 mL reaction tube, 0.2 mmol of 1,2-di-p-tolylethane-1,2-dione was dissolved in 2 mL of acetonitrile, and then 0.6 mmol of [bis(trifluoroacetoxy)iodo]benzene (PIFA) was added. The mixture was stirred under light for 12 hours. After the reaction was completed, the solvent was removed by rotary evaporation. The crude product was separated by silica gel column chromatography (petroleum ether: ethyl acetate = 1:10) to obtain the target product.
[0020] The target product structure and identification results are shown below:
[0021]
[0022] White solid (45.7 mg 90%), 1 H NMR(400MHz, CDCl3)(400MHz, CDCl3)δ11.40(s,1H),7.97(d,J=8.2Hz,2H),7.63(ddd,J=8.6 ,7.4,1.6Hz,1H),7.38(dd,J=8.0,1.5Hz,2H),6.89-6.92(m,2H),2.41(s,3H),2.28(s,3H). 13 C NMR (100MHz, CDCl3) δ199.6,192.8,161.7,145.6,144.2,132.3,130.0,129.8,122.1,119.8,116.9,22.1,22.6.
[0023] Example 3
[0024] The preparation method of the 1-(2-hydroxy-4-methoxyphenyl)-2-(4-methoxyphenyl)ethane-1,2-dione compound in this embodiment with the participation of light-induced PIFA is as follows:
[0025] In a 10 mL reaction tube, 0.2 mmol of 1,2-di(4-methoxyphenyl)ethane-1,2-dione was dissolved in 2 mL of acetonitrile, and then 0.8 mmol of [bis(trifluoroacetoxy)iodo]benzene (PIFA) was added. The mixture was stirred under light for 10 hours. After the reaction was completed, the solvent was removed by rotary evaporation. The crude product was separated by silica gel column chromatography (petroleum ether: ethyl acetate = 1:10) to obtain the target product.
[0026] The target product structure and identification results are shown below:
[0027]
[0028] White solid (33.2 mg, 58%), 1 H NMR (400MHz, CDCl3) (400MHz, CDCl3) δ11.55 (s, 1H), 8.22 (d, J = 8.2
[0029] Hz,2H),8.03(ddd,J=8.6,7.4,1.6Hz,1H),7.12(dd,J=8.0,1.5Hz,2H),6.68-6.60(m,2H),3.48(s,3H),3.41(s,3H). 13 C NMR (100MHz, CDCl3) δ199.9,193.6,167.8,166.4,166.3,135.1,130.9,125.8,118.7,117.9,114.6,110.2,55.8.
[0030] Example 4
[0031] The preparation method of the 1-(4-chloro-2-hydroxyphenyl)-2-(4-chloro-phenyl)ethane-1,2-dione compound in this embodiment with the participation of light-induced PIFA is as follows:
[0032] In a 10 mL reaction tube, 0.2 mmol of 1,2-bis(4-chlorophenyl)ethane-1,2-dione was dissolved in 2 mL of acetonitrile, and then 0.4 mmol of [bis(trifluoroacetoxy)iodo]benzene (PIFA) was added. The mixture was stirred under light for 12 hours. After the reaction was completed, the solvent was removed by rotary evaporation. The crude product was separated by silica gel column chromatography (petroleum ether: ethyl acetate = 1:10) to obtain the target product.
[0033] The target product structure and identification results are shown below:
[0034]
[0035] White solid (45.6 mg, 78%), 1 H NMR (400MHz, CDCl3) δ11.50 (s, 1H), 7.94 (d, J = 7.3Hz, 2H), 7.67 (t, J = 7.4Hz, 1 H),7.51(t,J=7.8Hz,2H),7.08(d,J=1.8Hz,1H),6.83(dd,J=8.6,1.9Hz,1H); 13 C NMR (100MHz, CDCl3) δ198.4,191.6,167.0,144.5,135.5,133.5,132.5,130.2,129.3,120.7,119.0,115.5.
[0036] Example 5
[0037] The preparation method of the 1-(4-chloro-2-hydroxyphenyl)-2-(4-bromo-phenyl)ethane-1,2-dione compound in this embodiment with the participation of light-induced PIFA is as follows:
[0038] In a 10 mL reaction tube, 0.2 mmol of 1,2-bis(4-bromophenyl)ethane-1,2-dione was dissolved in 2 mL of acetonitrile, and then 0.6 mmol of [bis(trifluoroacetoxy)iodo]benzene (PIFA) was added. The mixture was stirred under light for 12 hours. After the reaction was completed, the solvent was removed by rotary evaporation. The crude product was separated by silica gel column chromatography (petroleum ether: ethyl acetate = 1:10) to obtain the target product.
[0039] The target product structure and identification results are shown below:
[0040]
[0041] Yellow solid (53.2 mg, 70%), 1 H NMR (400MHz, CDCl3) δ11.46 (s, 1H), 8.11–7.90 (m, 2H), 7.82 (t, J = 7.5Hz, 1H), 7.67 (dd, J = 14.3, 6.3Hz, 3H), 7.01 (d, J = 8.9Hz, 1H). 13CNMR (100MHz, CDCl3) δ198.2,191.2,162.4,140.9,135.5,134.3,132.4,130.2,129.3,120.9,118.0,111.4.
[0042] Example 6
[0043] The preparation method of the 1-(2-hydroxynaphthyl-1-yl)-2-(naphthalene-1-yl)ethane-1,2-dione compound in this embodiment with the participation of light-induced PIFA is as follows:
[0044] In a 10 mL reaction tube, 0.2 mmol of 1,2-di(naphthalene-1-yl)ethane-1,2-dione was dissolved in 2 mL of acetonitrile, and then 0.8 mmol of [bis(trifluoroacetoxy)iodo]benzene (PIFA) was added. The mixture was stirred under light for 10 hours. After the reaction was completed, the solvent was removed by rotary evaporation. The crude product was separated by silica gel column chromatography (petroleum ether: ethyl acetate = 1:10) to obtain the target product.
[0045] The target product structure and identification results are shown below:
[0046]
[0047] White solid (40.3 mg, 62%), 1 H NMR(400MHz, CDCl3)δ11.46(s,1H),9.32-9.24(m,2H),8.35-8.32(m,2H),7.95 -7.73(m,5H),7.57-7.42(m,2H),7.11(d,J=8.4Hz,1H),6.89(t,J=7.6Hz,1H). 13 C NMR (100MHz, CDCl3) δ199.4,194.4,162.5,138.0,136.4,135.5,134.9,134.9,134.6,134 .0,130.2,130.2,129.7,128.9,128.1,127.3,125.9,124.9,124.5,119.8,118.7,117.2.
[0048] Example 7
[0049] The preparation method of the 1-(1-hydroxynaphthyl-2-yl)-2-(naphthalene-2-yl)ethane-1,2-dione compound in this embodiment with the participation of light-induced PIFA comprises the following steps:
[0050] In a 10 mL reaction tube, 0.2 mmol 1,2-(naphthalene-2-yl)-2-phenylethane-1,2-dione-dione was dissolved in 2 mL acetonitrile, and then 2 equivalents of [bis(trifluoroacetoxy)iodo]benzene (PIFA) were added. The reaction was stirred under light for 10 hours. After the reaction was completed, the solvent was removed by rotary evaporation. The crude product was separated by silica gel column chromatography (petroleum ether: ethyl acetate = 1:10) to obtain the target product.
[0051] The target product structure and identification results are shown below:
[0052]
[0053] White solid (42.6 mg, 65%), 1 H NMR(400MHz, CDCl3)(400MHz, CDCl3)δ11.30(s,1H),8.42(s,1H),8.11(d,J=8.6Hz,1H ),8.10–7.90(m,6H),7.68-7.60(m,3H),7.13(d,J=8.5Hz,1H),6.91(t,J=7.6Hz,1H). 13 C NMR (100MHz, CDCl3) δ199.3,192.0,163.4,134.7,133.7,133.4,132.5,132.4,131.7,129 .9,129.7,129.2,128.9,128.3,128.0,127.9,127.5,127.3,123.5,119.7,118.6,116.9.
[0054] Example 8
[0055] The preparation method of the 1-(2-hydroxy-5-toluene)-2-m-tolueneethane-1,2-dione compound in this embodiment with the participation of light-induced PIFA is as follows:
[0056] In a 10 mL reaction tube, 0.2 mmol of 1,2-dimethylbenzene-1,2-dione was dissolved in 2 mL of acetonitrile, and then 2 equivalents of [bis(trifluoroacetyloxy)iodo]benzene (PIFA) were added. The mixture was stirred under illumination for 12 hours. After the reaction was completed, the solvent was removed by rotary evaporation. The crude product was separated by silica gel column chromatography (petroleum ether: ethyl acetate = 1:10) to obtain the target product.
[0057] The target product structure and identification results are shown below:
[0058]
[0059] White solid (38.5 mg, 76%), 1 H NMR (400MHz, CDCl3) δ11.57(s,1H),7.86-7.57(m,3H),7.42-7.32(m,2H),7.20(d,J=7.9Hz,1H),6.69(t,J=7.7Hz,1H),2.26(s,3H),2.21(s,3H). 13 C NMR (100MHz, CDCl3) δ198.6,191.2,160.8,137.8,134.1,131.8,129.0,128.1,126.9,118.2,115.2,14.3,14.6.
[0060] Example 9
[0061] The method for synthesizing 1-([1,1'-biphenyl]-4-yl)-2-(3-hydroxy[1,1'-biphenyl]-4-yl)ethane-1,2-dione compound with the participation of light-induced PIFA in this embodiment comprises the following steps:
[0062] In a 10 mL reaction tube, 0.2 mmol 1-([1,1'-biphenyl]-4-yl)ethane-1,2-dione was dissolved in 2 mL acetonitrile, and then 2 equivalents of [bis(trifluoroacetoxy)iodo]benzene (PIFA) were added. The mixture was stirred under light for 16 hours. After the reaction was completed, the solvent was removed by rotary evaporation. The crude product was separated by silica gel column chromatography (petroleum ether:ethyl acetate=1:10) to obtain the target product.
[0063] The target product structure and identification results are shown below:
[0064]
[0065] White solid (45.6 mg, 60%); 1 H NMR (400MHz, CDCl3) δ11.35(s,1H),7.93-7.74(m,9H),7.47-7.28(m,8H). 13 C NMR (100MHz, CDCl3) δ199.3,191.9,162.8,152.9,146.8,140.8,137.2,137.1, 135.3,133.3,132.7,130.4,130.1,129.2,128.9,127.5,126.7,119.2,117.0.
Claims
1. A method for preparing a 2-hydroxybenzil compound with the participation of light-induced PIFA, characterized in that: The steps are as follows: under light conditions, [bis(trifluoroacetoxy)iodo]benzene and benzil are dissolved in acetonitrile for reaction, wherein the molar ratio of [bis(trifluoroacetoxy)iodo]benzene to benzil is 2-4:1; after the reaction is completed, the solvent is removed by rotary evaporation, and 2-hydroxybenzil compounds are separated by column chromatography.
2. The method for preparing 2-hydroxybenzil compounds involving light-induced PIFA according to claim 1, characterized in that: The structural formula of the 2-hydroxybenzil is, wherein R 1 is one of methyl, phenyl, fluorine, chlorine, bromine, nitro, and methoxy; R 2 It is one of methyl, ethyl, methoxy, fluorine, chlorine, bromine, nitro, nitrile, trifluoromethyl, trifluoromethoxy, phenyl, benzyl and dimethylamino.
3. The method for preparing 2-hydroxybenzil compounds involving light-induced PIFA according to claim 3, characterized in that: The benzil structural formula is, wherein R 1 It is one of methyl, phenyl, fluorine, chlorine, bromine, nitro and methoxy.
4. The method for preparing 2-hydroxybenzil compounds involving light-induced PIFA according to claim 4, characterized in that: Acetonitrile was used as solvent.
5. The method for preparing 2-hydroxybenzil compounds involving light-induced PIFA according to claim 5, characterized in that: The reaction time is 6-24 h.
6. The method for preparing 2-hydroxybenzil compounds with the participation of light-induced PIFA according to any one of claims 1 to 6, characterized in that: The reagents for column chromatography are petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 1: (10-100).