A method for preparing aryl / heteroaryl ketone compounds

Abstract

A preparation method of aryl / heteroaryl ketone compounds, the present application relates to the technical field of organic photoelectric synthesis.The present application solves the technical problem that the existing reaction technology is difficult to realize in-situ activation of aryl / heteroaryl formic acid and dehydroxymethyl coupling of alcohol compounds to prepare aryl / heteroaryl ketone compounds.Method: the present application continuously carries out illumination in the reaction system and passes in constant current, takes carboxylic acid and alcohol compound as the reactants, the iron catalyst is excited by light at the anode, at the same time, in-situ activation of nickel catalyst and carboxylic acid occurs at the cathode, and then reduction elimination process is carried out to obtain aryl / heteroaryl ketone compounds.The electrons provided by the current in the system of the present application are used as cheap and clean oxidants, which avoids the use of external oxidants, the reaction operation is simple, the condition is mild, and the aryl / heteroaryl ketone compounds prepared by the present application are used in the field of medicine.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organic photoelectrochemical synthesis, and particularly relates to a preparation method of aryl / heteroaryl ketone compounds. BACKGROUND

[0002] Aryl / heteroaryl ketone compounds exist widely in drugs, natural products and agricultural products, and the synthesis thereof is an important topic in chemical research, especially since heteroaryl ketone compounds are important components of many drug molecules. For example, progesterone is an important hormone involved in the female menstrual cycle of humans and other animals, supports pregnancy and embryo formation, and is the most important progestin. Furan diterpenoid is an antibacterial and anti-inflammatory active drug, and ketotifen has the effect of preventing the onset of exogenous, endogenous and mixed asthma.

[0003] The reaction of coupling alcohol and carboxylic acid compounds to generate ketone compounds has important academic and application values. Ketone compounds are basic structural units in organic synthesis and are widely used in the fields of drugs, fragrances, materials and pesticides. Traditional synthesis methods of ketone compounds usually rely on complex reaction conditions and valuable catalysts, and often require the use of metal catalysts or strong oxidizing and reducing reagents, which not only increases the synthesis cost but also brings environmental burden. Therefore, developing a simple, efficient and environmentally friendly synthesis route, especially through the coupling reaction of carboxylic acid and alcohol compounds, has become an important research direction in the field of organic chemistry. This reaction not only can provide new synthesis strategies, but also can reduce the dependence on toxic reagents, improve the sustainability of the reaction, and has wide industrial application prospects. SUMMARY

[0004] The present application solves the technical problem that the existing reaction technology cannot realize in-situ activation of aryl / heteroaryl formic acid and dehydroxymethylation coupling of alcohol compounds to prepare aryl / heteroaryl ketone compounds, and provides a preparation method of aryl / heteroaryl ketone compounds. With the aid of photoelectrochemical synthesis strategy, the reaction system is continuously irradiated and a constant current is passed, simple carboxylic acid and alcohol compounds are used as reactants, an alkoxy radical is formed through a ligand to metal charge transfer process of the iron catalyst after being excited by light at the anode, and then a beta-C-C bond of the alkoxy radical intermediate is broken to obtain an alkyl radical. At the same time, an aryl / heteroaryl acyl nickel compound intermediate is formed through an oxidative addition process of the nickel catalyst and the acid anhydride generated by in-situ activation of the carboxylic acid at the cathode. Then, the intermediate captures the alkyl radical, and then a reductive elimination process occurs to obtain an aryl / heteroaryl alkyl ketone product, and at the same time, the catalytic cycle of the nickel catalyst is completed through the change of valence.

[0005] A method for preparing aryl / heteroaryl ketone compounds, which is specifically carried out according to the following steps:

[0006] I. placing an anode electrode and a cathode electrode in a quartz tube, adding a carboxylic acid compound, an alcohol compound, diethyl pyrocarbonate, an iron catalyst, a nickel catalyst, a ligand and TBACl in an inert gas atmosphere, then adding an ultradry solvent, and sealing the system;

[0007] The structural general formula of the carboxylic acid compound is:

[0008] wherein Ar represents aryl or heteroaryl;

[0009] II. continuously irradiating the sealed system of step I under light irradiation with a wavelength of 390-395 nm, while continuously supplying a constant current and stirring to obtain a crude product;

[0010] III. removing the solvent from the crude product obtained in step II by reduced pressure distillation, and then separating and purifying the product by thin layer chromatography to obtain the aryl / heteroaryl ketone compound.

[0011] Further, the structural general formula of the alcohol compound in step I is: wherein R is aryl or alkyl.

[0012] Further, the TBACl in step I is electrolyte tetrabutylammonium chloride.

[0013] Further, the ultradry solvent in step I is ultradry acetone.

[0014] Further, the iron catalyst in step I is ferrous chloride tetrahydrate; and the nickel catalyst is nickel (II) chloride glycol dimethyl ether complex.

[0015] Further, the ligand in step I is 1,10-phenanthroline.

[0016] Further, the use amount ratio of the carboxylic acid compound to the ultradry solvent is 0.2 mmol:3 mL; the use amount ratio of the alcohol compound to the ultradry solvent is 0.6 mmol:3 mL; the use amount ratio of diethyl pyrocarbonate to the ultradry solvent is 0.4 mmol:3 mL; the use amount ratio of the iron catalyst to the ultradry solvent is 0.02 mmol:3 mL; the use amount ratio of the nickel catalyst to the ultradry solvent is 0.03 mmol:3 mL; the use amount ratio of the ligand to the ultradry solvent is 0.02 mmol:3 mL; and the use amount ratio of TBACl to the ultradry solvent is 0.4 mmol:3 mL.

[0017] Further, the anode electrode in step I is a carbon felt electrode, and the cathode electrode is a carbon felt electrode, and the specification of the carbon felt electrode is 15 mm x 10 mm x 2.0 mm.

[0018] Furthermore, in step 2, the current of the constant current was controlled to be 4 mA, the temperature of the condensation pump connected to the photoreactor was 16° C., the continuous power-on and illumination time was 12 hours; and TLC was used to monitor the reaction progress.

[0019] Furthermore, the solvent used for the thin layer chromatography separation and purification in step 3 is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 20:1.

[0020] The general reaction formula of the present invention is as follows:

[0021]

[0022] Wherein R is an alkyl group or an aryl group.

[0023] The reaction mechanism of the present invention is shown in FIG. Figure 3 shown.

[0024] Initially, the process starts with Fe(III) complex (A), which is excited by light to produce its excited state, the excited state [Fe III Cl4] - The catalyst undergoes a ligand-to-metal charge transfer (LMCT) process to generate alkoxy radicals, which then undergo a β-CC bond cleavage process to form an activated carbon-centered radical intermediate (C), while [Fe II Cl3] - Oxidized at the anode to recover [Fe III Cl4] - The cycle is completed. At the same time, the Ni(II) catalyst precursor is reduced in situ to generate a Ni(I) species (D). The intermediate D further undergoes oxidative addition with the anhydride to form an acyl Ni(III) species (E), which is then reduced to an acyl Ni(II) species (F) at the cathode. The carbon-centered free radical is captured by the Ni(II) intermediate F to generate a Ni(III) species (G), which then undergoes a reductive elimination process to obtain the target ketone product, while simultaneously forming a Ni(I) species (D) to complete the cycle.

[0025] Beneficial effects of the present invention:

[0026] Compared with the prior art, the present invention uses a simple, green and efficient method to synthesize aryl / heteroaryl ketone compounds, which has the following advantages:

[0027] (1) This reaction uses electrons provided by the current in the system as a cheap and clean oxidant, avoiding the use of external oxidants. The reaction operation is simple and the conditions are mild.

[0028] (2) The carboxylic acid compound, alcohol compound, diethyl pyrocarbonate, iron catalyst, nickel catalyst, ligand, TBACl and super dry solvent used in the reaction system are simple, cheap and commercially available compounds, and the carbon felt electrode used is also a relatively cheap electrode sheet, so that the reaction system is simple and economical.

[0029] (3) The reaction system substrate has a wide application range and can be used to synthesize various aryl / heteroaryl ketone compounds, and the reaction substrate can include aryl / heteroaryl carboxylic acid compounds, aryl alcohol compounds or alkyl alcohol compounds.

[0030] The aryl / heteroaryl ketone compound prepared by the method can be used in the field of medicine. BRIEF DESCRIPTION OF DRAWINGS

[0031] Figure 1 is a heteroaryl ketone compound (3-1) obtained in Example 1 1 H NMR spectrum;

[0032] Figure 2 is a heteroaryl ketone compound (3-1) obtained in Example 1 13 C NMR spectrum;

[0033] Figure 3 is a reaction mechanism diagram of the present application. DETAILED DESCRIPTION

[0034] DETAILED DESCRIPTION ONE: The preparation method of the aryl / heteroaryl ketone compound in the embodiment is specifically performed according to the following steps:

[0035] I. An anode electrode and a cathode electrode are placed in a quartz tube, and a carboxylic acid compound, an alcohol compound, diethyl pyrocarbonate, an iron catalyst, a nickel catalyst, a ligand and TBACl are added under an inert gas atmosphere, and then a super dry solvent is added, and the system is sealed;

[0036] The structure general formula of the carboxylic acid compound is:

[0037] wherein Ar represents aryl or heteroaryl;

[0038] II. The sealed system in step I is continuously irradiated under light with a wavelength of 390-395 nm, and a constant current is continuously supplied while stirring to obtain a crude product;

[0039] III. The crude product obtained in step II is subjected to vacuum distillation to remove the solvent, and then thin layer chromatography is used for separation and purification, and the obtained product is an aryl / heteroaryl ketone compound.

[0040] DETAILED DESCRIPTION TWO: The difference between the embodiment and the detailed description one is that the structure general formula of the alcohol compound in step I is: wherein R is aryl or alkyl. The rest is the same as in embodiment one.

[0041] Embodiment three: different from embodiment one or two is that the TBACl in step one is tetrabutylammonium chloride as electrolyte. The rest is the same as in embodiment one or two.

[0042] Embodiment four: different from any one of embodiment one to three is that the super dry solvent in step one is super dry acetone. The rest is the same as in any one of embodiment one to three.

[0043] Embodiment five: different from any one of embodiment one to four is that the iron catalyst in step one is ferrous chloride tetrahydrate; the nickel catalyst is nickel (II) chloride ethylene glycol dimethyl ether complex. The rest is the same as in any one of embodiment one to four.

[0044] Embodiment six: different from any one of embodiment one to five is that the ligand in step one is 1,10-phenanthroline. The rest is the same as in any one of embodiment one to five.

[0045] Embodiment seven: different from any one of embodiment one to six is that the ratio of the carboxylic acid compound to the super dry solvent in step one is 0.2 mmol:3 mL; the ratio of the alcohol compound to the super dry solvent is 0.6 mmol:3 mL; the ratio of diethyl pyrocarbonate to the super dry solvent is 0.4 mmol:3 mL; the ratio of the iron catalyst to the super dry solvent is 0.02 mmol:3 mL; the ratio of the nickel catalyst to the super dry solvent is 0.03 mmol:3 mL; the ratio of the ligand to the super dry solvent is 0.02 mmol:3 mL; the ratio of TBACl to the super dry solvent is 0.4 mmol:3 mL. The rest is the same as in any one of embodiment one to six.

[0046] Embodiment eight: different from any one of embodiment one to seven is that the anode electrode in step one is carbon felt electrode, and the cathode electrode is carbon felt electrode, and the specification of the carbon felt electrode is 15 mm x 10 mm x 2.0 mm. The rest is the same as in any one of embodiment one to seven.

[0047] Embodiment nine: different from any one of embodiment one to eight is that the constant current in step two is 4 mA, the temperature of the condensation pump connected to the photo reactor is 16℃, and the continuous power-on and light irradiation time is 12 hours; TLC is used to monitor the reaction progress. The rest is the same as in any one of embodiment one to eight.

[0048] Specific implementation ten: the difference between this implementation and one of the specific implementations one to nine is that the solvent used in the thin layer chromatography separation and purification in step three is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 20:1. The others are the same as one of the specific implementations one to nine.

[0049] The content of the application is not limited to the content of each of the above embodiments, and the combination of one or several specific embodiments can also achieve the purpose of the application.

[0050] Example 1:

[0051] The preparation method of the aryl / heteroaryl ketone compound in this embodiment is specifically carried out according to the following steps:

[0052] I. Place two carbon felt electrodes in a 10 mL quartz tube, and add 0.2 mmol of 3-thiophene carboxylic acid, 0.6 mmol of β-phenethyl alcohol, 0.4 mmol of diethyl pyrocarbonate, 0.02 mmol of FeCl 2. 4H2O, 0.03 mmol of NiCl 2. glyme, 0.04 mmol of 1,10-phenanthroline, and 0.4 mmol of TBACl, and then add 3 mL of ultradry acetonitrile solvent, and seal the system;

[0053] II. Continuously irradiate the sealed system in step I under 390-395 nm light, while continuously supplying a constant current of 4 mA, and the temperature of the condensation pump connected to the light reaction instrument is 16°C. Stir for 12 h, and monitor the reaction progress by TLC to obtain a crude product;

[0054] III. Remove the solvent from the crude product obtained in step II by vacuum distillation, and then separate and purify it by thin layer chromatography to obtain a product, which is identified as a heteroaryl ketone compound (3-1) by nuclear magnetic hydrogen spectrum, carbon spectrum, and mass spectrum, and its structural formula is:

[0055]

[0056] The purity is 99%, and the yield is 48%; and the nuclear magnetic data analysis is:

[0057] 1 H NMR (400 MHz, Chloroform-d) δ 8.10 (dd, J = 2.9, 1.3 Hz, 1H), 7.57 (dd, J = 5.1, 1.2 Hz, 1H), 7.36-7.31 (m, 2H), 7.31-7.24 (m, 4H), 4.18 (s, 2H).

[0058] 13C NMR (101 MHz, Chloroform-d) δ 191.99, 141.90, 134.50, 132.78, 129.48, 128.79, 127.40, 127.05, 126.48, 46.99.

[0059] Example 2:

[0060] The preparation method of the aryl / heteroaryl ketone compound of the present embodiment is specifically carried out according to the following steps:

[0061] I. 0.2 mmol of 1-methyl-1H-pyrrole-2-carboxylic acid, 0.6 mmol of β-phenethyl alcohol, 0.4 mmol of diethyl pyrocarbonate, 0.02 mmol of FeCl 2. 4H2O, 0.03 mmol of NiCl 2. glyme, 0.04 mmol of 1,10-phenanthroline and 0.4 mmol of TBACl, and 3 mL of ultradry acetonitrile solvent are added, and the system is sealed;

[0062] II. The sealed system of step I is continuously irradiated under 390-395 nm light, and a constant current of 4 mA is continuously supplied. The temperature of the condensing pump connected to the light reaction instrument is 16°C. The reaction progress is monitored by TLC, and the crude product is obtained after stirring for 12 h;

[0063] III. The crude product obtained in step II is subjected to vacuum distillation to remove the solvent, and then thin layer chromatography is used for separation and purification to obtain the product, which is identified as a heteroaryl ketone compound (3-2) by nuclear magnetic hydrogen spectrum, carbon spectrum and mass spectrum, and its structural formula is:

[0064]

[0065] The purity is 99%, and the yield is 58%. The nuclear magnetic data analysis is as follows:

[0066] 1 H NMR (400 MHz, Chloroform-d) δ 7.37-7.28 (m, 4H), 7.28-7.21 (m, 1H), 7.09-7.08 (M, 1H), 6.82-6.81 (M, 1H), 6.15-6.14 (M, 1H), 4.07 (s, 2H), 3.91 (s, 3H).

[0067] 13 C NMR (101 MHz, Chloroform-d) δ 188.47, 135.62, 131.59, 129.51, 128.60, 126.77, 120.00, 108.18, 46.03, 37.85.

[0068] Example 3:

[0069] The preparation method of the aryl / heteroaryl ketone compound in this embodiment is specifically carried out according to the following steps:

[0070] I. 0.2 mmol of 3-furan carboxylic acid, 0.6 mmol of β-phenethyl alcohol, 0.4 mmol of diethyl pyrocarbonate, 0.02 mmol of FeCl 2. 4H2O, 0.03 mmol of NiCl 2. glyme, 0.04 mmol of 1,10-phenanthroline and 0.4 mmol of TBACl, and then 3 mL of ultradry acetonitrile solvent is added, and the system is sealed;

[0071] II. The sealed system in step I is continuously irradiated under 390-395 nm light, and a constant current of 4 mA is continuously supplied, the temperature of the condensing pump connected with the light reaction instrument is 16°C, and stirring is performed for 12 h. The progress of the reaction is monitored by TLC, and a crude product is obtained;

[0072] III. The crude product obtained in step II is subjected to vacuum distillation to remove the solvent, and then thin layer chromatography is used for separation and purification to obtain a product, which is identified as a heteroaryl ketone compound (3-3) by nuclear magnetic hydrogen spectrum, carbon spectrum and mass spectrum, and the structural formula is:

[0073]

[0074] The purity is 99%, and the yield is 59%; the nuclear magnetic data analysis is as follows:

[0075] 1 H NMR (400 MHz, Chloroform-d) δ 7.94 (s, 1H), 7.34 (t, J = 1.7 Hz, 1H), 7.27-7.24 (m, 1H), 7.20 (d, J = 6.5 Hz, 4H), 6.70 (d, J = 1.9 Hz, 1H), 3.97 (s, 2H).

[0076] 13 C NMR (101 MHz, Chloroform-d) δ 192.42, 147.74, 144.24, 134.32, 129.43, 128.82, 127.15, 109.05, 47.68.

[0077] Example 4:

[0078] The preparation method of the aryl / heteroaryl ketone compound in this embodiment is specifically carried out according to the following steps:

[0079] One, under inert gas atmosphere, add 0.2mmol 1-methyl-4-indole carboxylic acid, 0.6mmol β-phenylethanol, 0.4mmol diethyl pyrocarbonate, 0.02mmol FeCl 2. 4H2O, 0.03mmol NiCl 2. glyme, 0.04mmol 1,10-phenanthroline and 0.4mmol TBACl, and then add 3mL of super dry acetonitrile solvent, and seal the system;

[0080] Two, continuously irradiate the sealed system of step one under 390-395nm light, while continuously passing 4mA constant current, and the temperature of the condensing pump connected to the light reaction instrument is 16℃, and stir for 12h, and monitor the reaction progress by TLC, to obtain a crude product;

[0081] Three, remove the solvent from the crude product obtained in step two by reduced pressure distillation, and then separate and purify by thin layer chromatography to obtain a product, which is identified as a heteroaryl ketone compound (3-4) by nuclear magnetic hydrogen spectrum, carbon spectrum and mass spectrum, and the structural formula is:

[0082]

[0083] The purity is 99% and the yield is 59%; and the nuclear magnetic data analysis is:

[0084] 1 H NMR (400 MHz, Chloroform-d) δ 7.87-7.85 (m, 1H), 7.54 (d, J = 8.2 Hz, 1H), 7.35-7.29 (m, 5H), 7.28-7.23 (m, 2H), 7.20 (d, J = 3.1 Hz, 1H), 4.41 (s, 2H), 3.82 (s, 3H).

[0085] 13 C NMR (101 MHz, Chloroform-d) δ 198.99, 137.76, 135.52, 131.94, 129.67, 128.63, 126.72, 123.06, 120.55, 114.62, 103.01, 46.31, 33.08.

[0086] Example 5:

[0087] The preparation method of the aryl / heteroaryl ketone compound in this embodiment is specifically carried out according to the following steps:

[0088] One, under inert gas atmosphere, add 0.2mmol 1-methyl-4-indole carboxylic acid, 0.6mmol β-phenylethanol, 0.4mmol diethyl pyrocarbonate, 0.02mmol FeCl 2.4 H2O, 0.03 mmol NiCl 2. glyme, 0.04 mmol 1,10-phenanthroline and 0.4 mmol TBACl, and 3 mL of ultradry acetonitrile solvent was added, and the system was sealed;

[0089] II. The sealed system of step I was continuously irradiated under 390-395 nm light, while a constant current of 4 mA was continuously supplied, the temperature of the condensing pump connected to the photochemical reactor was 16°C, and stirring was performed for 12 h. The progress of the reaction was monitored by TLC, and a crude product was obtained;

[0090] III. The crude product obtained in step II was subjected to vacuum distillation to remove the solvent, and then thin layer chromatography was used for separation and purification to obtain a product, which was identified as a heteroaryl ketone compound (3-5) by nuclear magnetic hydrogen spectrum, carbon spectrum and mass spectrum, and its structural formula was:

[0091]

[0092] The purity was 99% and the yield was 65%; and the nuclear magnetic data analysis was as follows:

[0093] 1 H NMR (400 MHz, Chloroform-d) δ 7.87-7.85 (m, 1H), 7.54 (d, J = 8.2 Hz, 1H), 7.35-7.29 (m, 5H), 7.28-7.23 (m, 2H), 7.20 (d, J = 3.1 Hz, 1H), 4.41 (s, 2H), 3.82 (s, 3H).

[0094] 13 C NMR (101 MHz, Chloroform-d) δ 198.99, 137.76, 135.52, 131.94, 129.67, 128.63, 126.72, 123.06, 120.55, 114.62, 103.01, 46.31, 33.08.

[0095] Example 6:

[0096] The preparation method of the aryl / heteroaryl ketone compound in this embodiment is specifically performed according to the following steps:

[0097] I. 0.2 mmol of benzoic acid, 0.6 mmol of 4-chloro-2-phenyl ethanol, 0.4 mmol of diethyl pyrocarbonate, 0.02 mmol of FeCl 2. 4 H2O, 0.03 mmol NiCl 2.glyme, 0.04 mmol 1,10-phenanthroline and 0.4 mmol TBACl, and then 3 mL of super-dry acetonitrile solvent was added, and the system was sealed;

[0098] II. The sealed system of step I was continuously irradiated under 390-395 nm light, while a constant current of 4 mA was continuously supplied, and the temperature of the condenser pump connected to the photochemical reactor was 16°C. The reaction was stirred for 12 h, and the progress of the reaction was monitored by TLC. The crude product was obtained.

[0099] III. The crude product obtained in step II was subjected to vacuum distillation to remove the solvent, and then thin layer chromatography was used for separation and purification to obtain the product, which was identified as an aryl ketone compound (3-6) by nuclear magnetic hydrogen spectrum, carbon spectrum and mass spectrum, and the structural formula thereof was:

[0100]

[0101] The purity was 99%, and the yield was 58%. The nuclear magnetic data analysis was as follows:

[0102] 1 H NMR (400 MHz, Chloroform-d) δ 7.99 (d, J = 7.1 Hz, 2H), 7.61-7.54 (m, 1H), 7.47 (dd, J = 8.4, 7.0 Hz, 2H), 7.30 (d, J = 8.4 Hz, 2H), 7.19 (d, J = 8.4 Hz, 2H), 4.26 (s, 2H).

[0103] 13 C NMR (101 MHz, Chloroform-d) δ 197.17, 136.49, 133.42, 132.99, 130.95, 128.86, 128.79, 128.58, 44.74.

[0104] Example 7:

[0105] I. 0.2 mmol of benzoic acid, 0.6 mmol of 4-methoxy-2-phenylethanol, 0.4 mmol of diethyl pyrocarbonate, 0.02 mmol of FeCl 2. 4H2O, 0.03 mmol of NiCl 2. glyme, 0.04 mmol 1,10-phenanthroline and 0.4 mmol TBACl, and then 3 mL of super-dry acetonitrile solvent was added, and the system was sealed;

[0106] II. The sealed system of step I was continuously irradiated under 390-395 nm light, while a constant current of 4 mA was continuously supplied, and the temperature of the condenser pump connected to the photochemical reactor was 16°C. The reaction was stirred for 12 h, and the progress of the reaction was monitored by TLC. The crude product was obtained.

[0107] III. The crude product obtained in step II was subjected to vacuum distillation to remove the solvent, and then purified by thin layer chromatography to obtain a product, which was identified as an aryl ketone compound (3-7) by nuclear magnetic hydrogen spectrum, carbon spectrum and mass spectrum, and had the following structural formula:

[0108]

[0109] The purity was 99%, and the yield was 42%; and the nuclear magnetic data analysis was as follows:

[0110] 1 H NMR (400 MHz, Chloroform-d) δ 8.01 (d, J = 7.1 Hz, 2H), 7.59-7.52 (m, 1H), 7.45 (t, J = 8.0 Hz, 2H), 7.18 (d, J = 6.5 Hz, 2H), 6.86 (d, J = 8.7 Hz, 2H), 4.22 (s, 2H), 3.78 (s, 3H).

[0111] 13 C NMR (101 MHz, Chloroform-d) δ 198.07, 158.60, 136.66, 133.20, 130.55, 128.71, 128.67, 126.55, 114.21, 55.32, 44.69.

[0112] Example 8:

[0113] The method for preparing an aryl / heteroaryl ketone compound in this example was specifically performed according to the following steps:

[0114] I. 0.2 mmol of benzoic acid, 0.6 mmol of 4-cyano-phenethyl alcohol, 0.4 mmol of diethyl pyrocarbonate, 0.02 mmol of FeCl 2. 4H2O, 0.03 mmol of NiCl 2. glyme, 0.04 mmol of 1,10-phenanthroline and 0.4 mmol of TBACl were added under an inert gas atmosphere, and 3 mL of ultradry acetonitrile solvent was further added, and the system was sealed;

[0115] II. The sealed system in step I was subjected to continuous irradiation under 390-395 nm light, while a constant current of 4 mA was continuously introduced, the temperature of the condensation pump connected with the light reaction instrument was 16°C, and the stirring was performed for 12 h. The reaction progress was monitored by TLC, and a crude product was obtained;

[0116] III. The crude product obtained in step II is subjected to vacuum distillation to remove the solvent, and then separated and purified by thin layer chromatography to obtain a product, which is identified as an aryl ketone compound (3-8) by nuclear magnetic hydrogen spectrum, carbon spectrum and mass spectrum, and has the structural formula:

[0117]

[0118] The purity is 99%, and the yield is 42%; and the nuclear magnetic data analysis is as follows:

[0119] 1 H NMR (400 MHz, Chloroform-d) δ 8.01-8.00 (m, 2H), 7.67-7.58 (m, 3H), 7.52-7.48 (m 2H), 7.39-7.37 (m, 2H), 4.37 (s, 2H).

[0120] 13 C NMR (101 MHz, Chloroform-d) δ 196.24, 140.03, 136.24, 133.77, 132.42, 130.61, 128.94, 128.52, 118.87, 111.02, 45.28.

[0121] Example 9:

[0122] The method for preparing an aryl / heteroaryl ketone compound in this example is specifically carried out according to the following steps:

[0123] I. Under an inert gas atmosphere, 0.2 mmol of benzoic acid, 0.6 mmol of cyclohexylmethanol, 0.4 mmol of diethyl pyrocarbonate, 0.02 mmol of FeCl 2. 4H2O, 0.03 mmol of NiCl 2. glyme, 0.04 mmol of 1,10-phenanthroline and 0.4 mmol of TBACl are added, and 3 mL of ultradry acetonitrile solvent is added, and the system is sealed;

[0124] II. The sealed system in step I is subjected to continuous irradiation under 390-395 nm light, while a constant current of 4 mA is continuously introduced, the temperature of the condensation pump connected with the light reaction instrument is 16°C, and stirring is performed for 12 h. The reaction progress is monitored by TLC to obtain a crude product;

[0125] III. The crude product obtained in step II is subjected to vacuum distillation to remove the solvent, and then separated and purified by thin layer chromatography to obtain a product, which is identified as an aryl ketone compound (3-8) by nuclear magnetic hydrogen spectrum, carbon spectrum and mass spectrum, and has the structural formula:

[0126]

[0127] Purity 99%, yield 36%; its NMR data analysis is:

[0128] 1 H NMR (400 MHz, Chloroform-d) δ 7.95 (d, J = 7.9 Hz, 2H), 7.54 (t, J = 7.3 Hz, 1H), 7.46 (t, J = 7.6 Hz, 2H), 3.27 (tt, J = 11.5, 3.2 Hz, 1H), 1.87 (td, J = 18.2, 17.3, 3.4 Hz, 4H), 1.79 - 1.70 (m, 1H), 1.58 - 1.21 (m, 5H).

[0129] 13 C NMR (101 MHz, Chloroform-d) δ 204.01, 136.40, 132.80, 128.65, 128.32, 45.69, 29.48, 26.02, 25.92.

[0130] The above-described embodiments are only a preferred scheme of the present application, and do not limit the present application in any form. Other variants and modifications can be made without departing from the technical scheme recited in the claims.

Claims

1. A method for preparing an aryl / heteroaryl ketone compound, characterized in that The method is specifically carried out in the following steps:

1. Place an anode electrode and a cathode electrode in a quartz tube, add a carboxylic acid compound, an alcohol compound, diethyl pyrocarbonate, an iron catalyst, a nickel catalyst, a ligand, and tetrabutylammonium chloride under an inert gas atmosphere, then add an ultra-dry solvent, and seal the system; The carboxylic acid compound has the general structural formula: wherein Ar represents an aryl or heteroaryl group; The alcohol compound has the general structural formula: , wherein R is an aryl group or an alkyl group; 2. Continuously irradiate the closed system in step 1 under light at a wavelength of 390-395 nm while continuously passing a constant current and stirring to obtain a crude product; 3. The crude product obtained in step 2 is subjected to reduced pressure distillation to remove the solvent, and then separated and purified by thin layer chromatography to obtain an aryl / heteroaryl ketone compound; The iron catalyst in step 1 is ferrous chloride tetrahydrate; the nickel catalyst is nickel (II) chloride ethylene glycol dimethyl ether complex; The ligand in step 1 is 1,10-phenanthroline; Step 2: Control the constant current to 4 mA; The general reaction formula of step 2 is: 。 2. The method for preparing an aryl / heteroaryl ketone compound according to claim 1, characterized in that The ultra-dry solvent in step 1 is ultra-dry acetone.

3. The method for preparing an aryl / heteroaryl ketone compound according to claim 1, characterized in that The amount ratio of the carboxylic acid compound to the ultra-dry solvent in step 1 is 0.2 mmol: 3 mL; the amount ratio of the alcohol compound to the ultra-dry solvent is 0.6 mmol: 3 mL; the amount ratio of diethyl pyrocarbonate to the ultra-dry solvent is 0.4 mmol: 3 mL; the amount ratio of the iron catalyst to the ultra-dry solvent is 0.02 mmol: 3 mL; the amount ratio of the nickel catalyst to the ultra-dry solvent is 0.03mmol: 3 mL; the amount ratio of the ligand to the ultra-dry solvent is 0.02 mmol: 3 mL; and the amount ratio of tetrabutylammonium chloride to the ultra-dry solvent is 0.4 mmol: 3 mL.

4. The method for preparing an aryl / heteroaryl ketone compound according to claim 1, characterized in that In step 1, the anode electrode is a carbon felt electrode, and the cathode electrode is a carbon felt electrode. The specifications of the carbon felt electrode are 15 mm × 10 mm × 2.0 mm.

5. The method for preparing an aryl / heteroaryl ketone compound according to claim 1, characterized in that Step 2: Control the temperature of the condensation pump connected to the light reactor to 16°C, and continuously power on and illuminate for 12 hours; monitor the reaction progress using TLC.

6. The method for preparing an aryl / heteroaryl ketone compound according to claim 1, characterized in that The solvent used for the thin layer chromatography separation and purification in step 3 is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 20:1.

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