Process for the preparation of aromatic carbonyl compounds by electrochemical oxidation and aromatic carbonyl compounds

Abstract

The application discloses a method for electro-oxidizing aromatic carbonyl compounds and the aromatic carbonyl compounds. The method comprises the following steps: in a protective atmosphere, under the condition of electricity, a compound containing a benzyl group, an electrolyte, a metal catalyst, water, and an organic solvent are subjected to an electro-oxidation carbonylation reaction, and post-treatment is performed to obtain the aromatic carbonyl compound; the method is capable of directly converting C-H in the compound containing the benzyl group into a high-value-added small organic molecule through oxidation, and has good tolerance to various sensitive functional groups. The electrochemical synthesis method has the characteristics of mild reaction condition, cleanness and greenness, and simple reaction operation.

Description

Technical Field

[0001] This invention relates to the field of organic electrochemical synthesis, and more specifically, to a method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction and the aromatic carbonyl compounds themselves. Background Technology

[0002] Carbonyl compounds are important organic skeletons and key synthetic precursors in organic chemistry, materials chemistry, and medicinal chemistry, possessing significant application value. Many new methods for preparing carbonyl compounds have been reported, among which the direct oxidation of aromatic compounds is a relatively simple and efficient method. The direct oxidation of aromatic hydrocarbons to CH4 is an ideal route for synthesizing aryl carbonyl compounds.

[0003] Traditional synthetic methods generally suffer from limited substrate scope, require the use of toxic noble metals, exhibit poor selectivity, and lack tolerance to functional groups, thus restricting their industrial application potential. Therefore, developing sustainable and efficient methods for the synthesis of aryl ketones is of significant scientific and practical value. Meanwhile, electrosynthesis has been identified as a more ideal route, avoiding the use of stoichiometric redox reagents in organic synthesis. Consequently, the combination of oxidation and electrosynthesis has attracted considerable attention. Summary of the Invention

[0004] To address the problems in existing technologies, this invention proposes a method for preparing aromatic carbonyl compounds via electrooxidative carbonylation. This invention selects substrates with significant and unique regioselectivity (compounds containing benzyl groups) and directly carbonylates the CH groups in these compounds via metal-catalyzed electrooxidation. A variety of novel and useful carbonyl compounds have been successfully synthesized from different substrates; these carbonyl compounds are not easily obtained using traditional methods. This electrochemical synthesis method features mild reaction conditions, is clean and environmentally friendly, and has simple operation.

[0005] One objective of this invention is to provide a method for preparing aromatic carbonyl compounds via electrochemical oxidation, comprising the following steps: under a protective atmosphere and under electrostatic conditions, an electrochemical carbonylation reaction is carried out in an organic solvent involving a benzyl-containing compound, an electrolyte, a metal catalyst, water, an alcohol or alcohol ether, followed by post-treatment to obtain the aromatic carbonyl compound; wherein the benzyl-containing compound is selected from at least one compound shown in Formula 1 or Formula 2.

[0006]

[0007] In Equation 1,

[0008] n≥1; R is alkyl, cycloalkyl, halogen, ketone, hydroxyl, amide, alkoxy, substituted or unsubstituted aryl. Wherein, R' is selected from hydrogen, unsubstituted alkyl, substituted or unsubstituted alicyclic group, substituted or unsubstituted heterocyclic group; Wherein, R" is selected from substituents containing amide groups, substituents containing NBoc groups, alkyl groups, substituted or unsubstituted aryl groups;

[0009] R1 is hydrogen, halogen, alkoxy, phenoxy, substituted or unsubstituted aryl, alkyl, cyano, or ester group; R2 is hydrogen or alkoxy; R3 is hydrogen or alkoxy.

[0010] In Equation 2,

[0011] M is a C4-C6 cycloalkyl or a C3-C6 heterocyclic group; R4 is hydrogen, alkoxy, or C1-C5 alkyl; R5 is a substituent on ring M, selected from substituted or unsubstituted phenyl or alkyl groups; R6 is hydrogen or C1-C5 alkyl; R7 is hydrogen or C1-C3 alkyl.

[0012] In the method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to the present invention, preferably, the compound containing benzyl is selected from the compounds shown in Formula 1:

[0013]

[0014] In Equation 1, n is selected from integers from 1 to 6;

[0015] R is a C1-C5 alkyl group, a C3-C6 cycloalkyl group, or a substituted phenyl group. R' is selected from hydrogen and C1-C5 alkyl groups;

[0016] R1 is a halogen, alkoxy, phenoxy, cyano, or C1-C3 ester group; R2 is hydrogen or a C1-C3 alkoxy group; R3 is hydrogen.

[0017] Preferably, in Formula 1, n is selected from integers from 1 to 3;

[0018] R is a C1-C3 alkyl group, a C3-C4 cycloalkyl group, an oxygen-substituted phenyl group, or a halogen-substituted phenyl group. R' is selected from hydrogen and C1-C3 alkyl groups;

[0019] More preferably, the benzyl-containing compound is selected from the compounds shown below:

[0020]

[0021] In the method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to the present invention, preferably, the compound containing benzyl is selected from the compounds shown in Formula 1:

[0022]

[0023] In Formula 1, n is selected from integers from 1 to 6; preferably, n is selected from integers from 1 to 4.

[0024] R is a C1-C5 alkyl, halogen, ketone, hydroxyl, amide, or C1-C3 alkoxy group;

[0025] R1 is a C1-C3 alkoxy group; R2 is hydrogen or a C1-C3 alkoxy group; R3 is hydrogen.

[0026] More preferably, the benzyl-containing compound is selected from the compounds shown below:

[0027]

[0028] Alternatively, the compound containing a benzyl group is selected from the compounds shown in Formula 1:

[0029]

[0030] In Formula 1, n is selected from integers from 1 to 6; preferably, n is selected from integers from 1 to 4.

[0031] R is Wherein, R' is selected from hydrogen, unsubstituted C1-C5 alkyl, substituted or unsubstituted six-membered alicyclic group, substituted or unsubstituted heterocyclic group;

[0032] R1 is a C1-C3 alkoxy group; R2 is hydrogen; R3 is hydrogen;

[0033] Preferably, the benzyl-containing compound is selected from the compounds shown below:

[0034]

[0035] In the method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to the present invention, preferably, the compound containing benzyl is selected from the compounds shown in Formula 1:

[0036]

[0037] In Formula 1, n is selected from integers from 1 to 6; preferably, n is selected from integers from 1 to 4.

[0038] R is Wherein, R" is selected from substituents containing amide groups, substituents containing NBoc groups, alkyl groups, substituted or unsubstituted phenyl groups;

[0039] R1 is a C1-C3 alkoxy group; R2 is hydrogen; R3 is hydrogen;

[0040] Preferably, the benzyl-containing compound is selected from the compounds shown below:

[0041]

[0042] In the method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to the present invention, preferably, the compound containing benzyl is selected from the compounds shown in Formula 1:

[0043]

[0044] In Formula 1, n is selected from integers from 1 to 6; preferably, n is selected from integers from 1 to 5.

[0045] R is a C1-C5 alkyl group. Wherein, R' is selected from hydrogen and unsubstituted C1-C3 alkyl groups;

[0046] R1 is a substituted or unsubstituted phenyl group; R2 is hydrogen; R3 is hydrogen; preferably, R1 is a phenyl group, an ester-substituted phenyl group, a halogen-substituted phenyl group, or a cyano-substituted phenyl group.

[0047] More preferably, the compound containing a benzyl group is selected from the compounds shown in Formula 1:

[0048] or,

[0049] The compound containing a benzyl group is selected from the compounds shown in Formula 1:

[0050]

[0051] In Formula 1, n is selected from integers from 1 to 6; preferably, n is selected from integers from 1 to 5.

[0052] R is a C1-C5 alkyl group, or a C1-C3 alkoxy-substituted phenyl group. Wherein, R' is selected from hydrogen;

[0053] R1 is an alkyl group; R2 is hydrogen; R3 is hydrogen; preferably, R1 is a C1-C5 alkyl group;

[0054] More preferably, the compound containing a benzyl group is selected from the compounds shown in Formula 1:

[0055]

[0056] In the method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to the present invention, preferably, the compound containing benzyl is selected from the compounds shown in Formula 1:

[0057]

[0058] In Equation 1, n is 1;

[0059] R is a substituted or substituted aryl group; preferably phenyl, thiophene, biphenyl, halogen-substituted phenyl, C1-C3 alkyl-substituted phenyl, alkoxy-substituted phenyl, oxytrifluoromethyl-substituted phenyl, or C1-C3 ester-substituted phenyl.

[0060] R1 is hydrogen; R2 is hydrogen; R3 is hydrogen;

[0061] More preferably, the benzyl-containing compound is selected from the compounds shown below:

[0062]

[0063] In the method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to the present invention, preferably, the compound containing benzyl is selected from the compound shown in Formula 2, specifically:

[0064]

[0065] In the method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to the present invention, preferably, the protective atmosphere is selected from Ar gas;

[0066] The electrolyte is selected from at least one of hexafluorophosphate and halide salts; preferably, the halide salt is selected from at least one tetraalkyl halide salt; the hexafluorophosphate is selected from potassium hexafluorophosphate; more preferably, the tetraalkyl halide salt is selected from at least one of tetrabutylammonium tetrafluoroborate, tetrabutylammonium chloride, and tetrabutylammonium hexafluorophosphate; and / or,

[0067] The organic solvent is selected from at least one of amide solvents, nitrile solvents, and sulfoxide solvents; preferably, the organic solvent is selected from at least one of N,N-dimethylformamide, N,N-dimethyl sulfoxide, and acetonitrile; and / or,

[0068] The alcohol is selected from at least one of methanol, ethanol, and isopropanol; and / or,

[0069] The alcohol ether is selected from at least one of ethylene glycol methyl ethers; and / or,

[0070] The metal catalyst is selected from inexpensive metal catalysts, preferably from at least one of nickel trifluoromethanesulfonate, cobalt trifluoromethanesulfonate, iron trifluoromethanesulfonate, manganese trifluoromethanesulfonate, copper trifluoromethanesulfonate, cerium trifluoromethanesulfonate, and chromium trifluoromethanesulfonate.

[0071] The molar ratio of the electrolyte to the benzyl-containing compound is 1:50% to 100%; and / or,

[0072] The concentration of the benzyl-containing compound in the organic solvent is 0.05–0.2 mol / L; and / or,

[0073] The molar ratio of the metal catalyst to the benzyl-containing compound is 5% to 50%:1; preferably 5% to 20%:1.

[0074] Preferably,

[0075] When the reaction is carried out using a system of water and organic solvent, the volume ratio of water to organic solvent is 1:5 to 50.

[0076] When the reaction is carried out using a system of alcohol and organic solvent, the volume ratio of alcohol to organic solvent is 1:1 to 20.

[0077] When the reaction is carried out using a system of alcohol ethers and organic solvents, the volume ratio of alcohol ethers to organic solvents is 1:1 to 20.

[0078] In the method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to the present invention, a constant current is applied during the electrooxidative carbonylation reaction, preferably...

[0079] The constant current is 1-30mA; and / or,

[0080] The energizing reaction time is 8-40 hours; and / or,

[0081] The energized reaction temperature is 10-70℃; and / or,

[0082] More preferably, the constant current is 5-20mA; and / or,

[0083] The energizing reaction time is 10-36 hours; and / or,

[0084] The energized reaction temperature is 10-60℃; and / or,

[0085] In the electro-oxidative carbonylation reaction, the cathode material is selected from carbon felt, nickel foam, cobalt, niobium, and platinum sheet; the anode material is selected from carbon felt and platinum sheet; and / or,

[0086] The post-processing includes rotary evaporation and column chromatography;

[0087] Preferably,

[0088] When the reaction is carried out using a system of water and organic solvents, the reaction temperature is 10-60℃.

[0089] When the reaction is carried out using a system of alcohols and organic solvents, the reaction temperature is 20-60℃.

[0090] When the reaction is carried out using a system of alcohols, ethers, and organic solvents, the reaction temperature is 20-60℃.

[0091] A second objective of this invention is to provide an aromatic carbonyl compound prepared by the electrochemical oxidation reaction described in one objective of this invention, wherein the aromatic carbonyl compound has the following general structural formula:

[0092]

[0093] In Formula 3, n, R, R1, R2, and R3 correspond to the same values ​​as n, R, R1, R2, and R3 in one of the objectives of this invention.

[0094] In Formula 4, the carbonyl group on ring M refers to the carbonyl group formed by the oxidation of the carbon atom on ring M adjacent to the benzene ring; R4, R5, R6, and R7 are the same as those in one of the objectives of this invention.

[0095] In Formula 5, R, R1, R2, and R3 correspond to the same R, R1, R2, and R3 in one of the objectives of this invention;

[0096] Preferably, the aromatic carbonyl compound is:

[0097]

[0098]

[0099] A third objective of this invention is to provide the application of aromatic carbonyl compounds prepared by the method described in one objective of this invention, or aromatic carbonyl compounds described in another objective of this invention, as substrates for the synthesis of drug molecules containing aromatic aldehyde and ketone derivatives.

[0100] The endpoints and any values ​​of the ranges disclosed in this invention are not limited to the precise ranges or values; these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein. In the following, various technical solutions can, in principle, be combined with each other to obtain new technical solutions, which should also be considered as specifically disclosed herein.

[0101] Compared with the prior art, the present invention has at least the following advantages:

[0102] This invention enables selective electrolysis of reaction substrates by adjusting the magnitude of the current and the electrode material and catalyst type of the anode. It is applicable to polysubstituted benzene rings, biphenyls, heterocycles, etc., and is compatible with ester groups, amides, halogens, and aldehyde / ketone groups to obtain aromatic aldehydes and ketones in high yields.

[0103] The method of this invention has high tolerance to substrate functional groups and exhibits good reactivity for different substituents, whether electron-withdrawing or electron-donating groups. The target products have high yields and selectivity, and it also shows good compatibility with complex late-modification drug molecules and natural products.

[0104] In summary, this invention a) converts CH in compounds directly containing benzyl groups into high-value-added small organic molecules, exhibiting good tolerance to various sensitive functional groups, such as carboxylic acids, amides, amino acids, esters, halogens, alcohols, and aldehydes; b) possesses good chemical and site selectivity; c) can oxidatively modify natural compounds and drug derivatives; and d) utilizes electrochemistry as an efficient and scalable preparation technique with promising industrial applications. The electrochemical synthesis method of electrolytic oxidation of the reaction substrate in this invention features mild reaction conditions, clean and environmentally friendly operation, and simple reaction procedures. Detailed Implementation

[0105] The present invention will now be described in detail with reference to specific embodiments. It should be noted that the following embodiments are only used to further illustrate the present invention and should not be construed as limiting the scope of protection of the present invention. Some non-essential improvements and adjustments made by those skilled in the art based on the content of the present invention are still within the scope of protection of the present invention.

[0106] Furthermore, various embodiments of the present invention can be combined in any way, as long as they do not violate the spirit of the present invention. The resulting technical solutions are part of the original disclosure of this specification and also fall within the protection scope of the present invention.

[0107] Unless otherwise specified, the raw materials used in the examples and comparative examples are all disclosed in the prior art, such as those that can be directly purchased or prepared according to the preparation methods disclosed in the prior art.

[0108] Example 1

[0109] In a 15 mL reaction tube, fixed electrodes were used: anode was carbon felt (GF, 10 mm × 15 mm × 5 mm), and cathode was a platinum sheet (Pt, 10 mm × 15 mm × 0.2 mm). A benzyl-containing compound (0.25 mmol, 1.0 equivalent), KPF6 (46.0 mg, 0.25 mmol, 1.0 equivalent), Ni(OTf)2 (8.9 mg, 0.025 mmol, 10% mol), and a magnetic flux were added to the reaction tube. The tube was then evacuated three times under an Ar atmosphere, and water (250 μL) and acetonitrile (5.0 mL) were added using a syringe. The reaction was carried out at a constant current of 10.0 mA at 50 °C with an Ar balloon for 12 hours. After the reaction was complete, the mixture was evaporated to dryness and concentrated under vacuum. The crude product was purified by column chromatography to obtain the desired product.

[0110] The following are compounds containing a benzyl group:

[0111]

[0112]

[0113] The results of the aromatic aldehydes and ketones prepared in Example 1 are as follows:

[0114]

[0115]

[0116] As shown above, the above reaction readily yields the desired product from functional groups that are highly sensitive to electro-oxidation conditions, such as aromatic hydrocarbons containing carboxyl groups, aldehydes, hydroxyl groups, and iodides, indicating that the electro-oxidation process has good functional group compatibility. In addition, heterocyclic compounds, such as thiophene, benzothiophene, furan, benzofuran, and aza-aryl rings, can also be converted to carboxylated products in high yields. It is noteworthy that this method is also applicable to simple polysubstituted benzene rings.

[0117] Examples 2-19

[0118] Examples 2-19 show that the reaction conditions were changed and the yields were compared.

[0119] Reaction conditions: substrate 1a (0.25 mmol), potassium hexafluorophosphate (0.25 mmol), nickel trifluoromethanesulfonate (10% mol), water (270 μL), acetonitrile (4 mL), platinum sheet as cathode, carbon felt as anode, electrolysis at constant current for 24 hours at 50 °C under argon atmosphere (I = 10 mA).

[0120]

[0121] The changes in reaction conditions and their yields are shown in the table below:

[0122] Table 1

[0123]

[0124]

[0125] The yields in Table 1 above are the yields from the initial NMR spectrum.

[0126] As shown in Table 1 above, the yield of aromatic hydrocarbon oxidation under the reaction conditions of this invention is as high as 73%. A series of control experiments show that using other Ni(II) salts with different anions, such as NiCl2 and Ni(ClO4)2, significantly reduces the product yield, and changing to other electrolytes also significantly reduces the yield. Using N,N-dimethylformamide (DMF) and dimethyl sulfoxide (DMSO) as reaction solvents does not produce good reaction results. Except for platinum sheet as the cathode material, which yields 73%, other cathode materials such as nickel sheet and carbon felt do not perform well. Air conditions are also not as good as using water as the oxygen source. Furthermore, control experiments show that no oxidation products are generated without electricity or water.

[0127] The reaction mechanism of this invention is as follows:

[0128]

[0129] The reaction of this invention may be a pairwise electrochemical oxidation mechanism. Taking 38a, a nickel catalyst, as an example, 38a is anolylated via single-electron transfer (SET) to generate a radical cation M-3 (detected by MS), which then loses a proton to generate a benzyl radical M-4. Simultaneously, the Ni(II) species undergoes single-electron reduction at the cathode to generate a Ni(I) intermediate, which can activate O2 to generate a Ni(II)-superoxide species M-1. This Ni-superoxide species M-1 is then further activated by single-electron reduction to provide a catalytically active Ni(II)-peroxide species M-2, which exhibits oxyenzyme-like properties, transferring an oxygen atom to intermediate M-4. The resulting reduced Ni(O) species is then anolylated to regenerate the Ni(II) salt, completing the catalytic cycle and forming the final product 38. The reaction of this invention also incorporates water, making it more environmentally friendly and safer than existing electrochemical oxidation reactions.

[0130] The parameters of the partially carbonylated products synthesized in this invention are as follows:

[0131]

[0132] 4-(4-Iodophenyl)-4-oxobutanoic acid(1)

[0133] Appearance: White solid. MPa: 177-178℃. 1 H NMR (400MHz, DMSO-d6) δ12.2(s,1H),7.93-7.91(m,2H),7.74-7.72(m,2H),3.21(t,J=6.4Hz,2H),2.57(t,J=6.4Hz,2H). 13C NMR (100MHz, DMSO-d6) δ198.6,174.2,138.1,136.2,130.1,102.3,33.5,28.3.

[0134]

[0135] 4-(4-Bromophenyl)-4-oxobutanoic acid(2)

[0136] White solid. MPa: 149-150℃. 1 H NMR (400MHz, Chloroform-d) δ7.85-7.83(m,2H),7.62-7.60(m,2H),3.27(t,J=6.8Hz,2H),2.81(t,J=6.8Hz,2H). 13 C NMR (100MHz, Chloroform-d) δ197.0,178.4,135.2,132.1,129.7,128.7,33.2,28.0.

[0137]

[0138] 4-(4-Chlorophenyl)-4-oxobutanoic acid(3)

[0139] Appearance: White solid. MPa: 149-150℃. 1 H NMR (400MHz, Chloroform-d) δ7.95-7.88(m,2H),7.48-7.40(m,2H),3.27(t,J=6.4Hz,2H),2.81(t,J=6.4Hz,2H). 13 C NMR (100MHz, Chloroform-d) δ196.8,178.6,140.0,134.8,129.6,129.1,33.3,28.1.

[0140]

[0141] 4-(4-fluorophenyl)-4-oxobutanoic acid(4)

[0142] Appearance: White solid. Mp: 100-101℃. 1H NMR (400MHz, Chloroform-d) δ8.02–7.99(m,2H),7.17–7.09(m,2H),3.28(t,J=6.4Hz,2H),2.81(t,J=6.4Hz,2H). 13 C NMR(100MHz,Chloroform-d)δ196.4,179.0,167.3,164.8(d,J C-F =254.0Hz),132.98,132.95,(d,J C-F =3.0Hz)130.88,130.79,(d,J C-F =9.0Hz)116.0,115.8,(d,J C-F =22.0Hz)33.17,28.13. 19 FNMR(376MHz,Chloroform-d)δ-104.74.

[0143]

[0144] 4-oxo-4-(p-tolyl)butanoic acid(5)

[0145] Appearance: White solid. MPa: 128-129℃. 1 H NMR (400MHz, Chloroform-d) δ7.92–7.84(m,2H),7.29–7.23(m,2H),3.29(t,J=6.6Hz,2H),2.80(t,J=6.6Hz,2H),2.41(s,3H). 13 C NMR (100MHz, Chloroform-d) δ197.6,179.1,144.3,134.0,129.5,128.3,33.2,28.2,21.8.

[0146]

[0147] 4-(4-Methoxyphenyl)-4-oxobutanoic acid(6)

[0148] Appearance: White solid. MPa: 48-49℃. 1 H NMR (400MHz, DMSO-d6) δ12.09(s,1H),7.97-7.95(m,2H),7.06-7.03(m,2H),3.84(s,3H),3.19(t,J=6.4Hz,2H),2.55(t,J=6.4Hz,2H).13 C NMR (100MHz, DMSO-d6) δ196.8,173.9,163.1,130.1,129.4,113.9,55.5,32.6,27.9.

[0149]

[0150] Methyl 4-(4-bromophenyl)-4-oxobutanoate(7)

[0151] Appearance: Colorless oily liquid. 1 H NMR (400MHz, Chloroform-d) δ7.84-7.82(m,2H),7.61-7.58(m,2H),3.69(s,3H),3.26(t,J=6.4Hz,2H),2.75(t,J=6.4Hz,2H). 13 C NMR (100MHz, Chloroform-d) δ197.2,173.3,135.3,132.1,129.7,128.5,52.0,33.4,28.0.

[0152]

[0153] Methyl 4-(4-methoxyphenyl)-4-oxobutanoate(8)

[0154] Appearance: White solid. MPa: 47-48℃. 1 HNMR(400MHz,Chloroform-d)δ7.97-7.95(m,2H),6.94-6.92(m,2H),3.87(s,3H),3.70(s,3H),3.27(t,J=6.8Hz,2H),2.75(t,J=6.8Hz,2H). 13 CNMR(100MHz,Chloroform-d)δ196.7,173.7,163.7,130.4,129.8,113.9,55.6,52.0,33.2,28.3.

[0155]

[0156] 4-(4-Methoxyphenyl)-N,N-dimethyl-4-oxobutanamide(9)

[0157] Appearance: Yellow solid. MPa: 177-178℃. 1H NMR (400MHz, Chloroform-d) δ8.00-7.98(m,2H),6.90-6.91(m,2H),3.85(s,3H),3.30(t,J=6.4Hz,2H),3.08(s,3H),2.95(s,3H),2.75(t,J=6.4Hz,2H). 13 C NMR(100MHz,Chloroform-d)δ198.0,172.1,163.6,130.5,130.1,113.8,55.6,37.3,35.7,33.4,27.5.HR-MS(ESI)m / z calc.for C 13 H 17 NO3Na[M+Na] + :258.1106,found:258.1093.

[0158]

[0159] 4-(4-Methoxyphenyl)-4-oxobutanal(10)

[0160] Appearance: Yellow oily liquid. 1 H NMR (400MHz, Chloroform-d) δ9.89 (s, 1H), 7.97-7.95 (m, 2H), 6.94-6.92 (m, 2H), 3.86 (s, 3H), 3.27 (t, J = 6.4Hz, 2H), 2.90 (t, J = 6.4Hz, 2H). 13 C NMR (100MHz, Chloroform-d) δ201.1,196.5,163.8,130.5,129.6,113.9,55.6,37.8,30.8.

[0161]

[0162] 4-Methoxy-1-(4-methoxyphenyl)butan-1-one(11)

[0163] Appearance: Brown oily liquid. 1 H NMR(400MHz,Chloroform-d)δ7.96-7.94(m,2H),6.93-6.91(m,2H),3.86(s,3H ),3.45(t,J=6.4Hz,2H),3.33(s,3H),3.01(t,J=7.2Hz,2H),2.03-1.97(m,2H). 13C NMR (100MHz, Chloroform-d) δ198.7,163.5,130.4,130.3,113.8,72.0,58.7,55.6,34.8,24.5.

[0164]

[0165] 4-(4-Methoxyphenyl)-4-oxobutyl acetate(12)

[0166] Appearance: White solid. MPa: 60-61℃. 1 HNMR (400MHz, Chloroform-d) δ7.95-7.93(m,2H),6.94-6.92(m,2H),4.16(t,J=6.4Hz,2H),3.86(s,3H),3.00(t,J=7.2Hz,2H),2.08(m,2H),2.03(s,3H). 13 C NMR(100MHz,Chloroform-d)δ197.8,171.2,163.6,130.4,130.1,113.9,64.0,55.6,34.6,23.5,21.1.HR-MS(ESI)m / z calc.for C 13 H 17 O4[M+H] + :237.1127,found:237.1125.

[0167]

[0168] 4-(4-Methoxyphenyl)-4-oxobutyl benzoate(13)

[0169] Appearance: White solid. Mp: 95-96℃. 1 HNMR(400MHz,Chloroform-d)δ8.04-8.02(m,2H),7.96-7.94(m,2H),7.57-7.53(m,1H),7.45-7.41 (m,2H),6.93-6.91(m,2H),4.42(t,J=6.4Hz,2H),3.85(s,3H),3.10(t,J=7.2Hz,2H),2.23(m,2H). 13C NMR(100MHz,Chloroform-d)δ197.7,166.7,163.6,133.0,130.4,130.0,129.7,128.5,113.9,64.5,55.6,34.7,23.6.HR-MS(ESI)m / z calc.for C 18 H 19 O4[M+H] + :299.1283,found:299.1277.

[0170]

[0171] 4-Chloro-1-(4-methoxyphenyl)butan-1-one(14)

[0172] Appearance: Brown oily liquid. 1 H NMR (400MHz, Chloroform-d) δ7.97-7.94(m,2H),6.95-6.92(m,2H),3.86(s,3H),3.67(t,J=6.4Hz,2H),3.12(t,J=7.2Hz,2H),2.24-2.18(m,2H). 13 C10 NMR (100MHz, Chloroform-d) δ 197.6, 163.7, 130.4, 130.0, 113.9, 55.6, 44.9, 35.0, 27.1. Compound data are consistent with literature.

[211] .

[0173]

[0174] 4-Hydroxy-1-(4-methoxyphenyl)butan-1-one(15)

[0175] Appearance: White solid. MPa: 55-56℃. 1 HNMR(400MHz,Chloroform-d)δ7.97-7.95(m,2H),6.94-6.92(m,2H),3.87(s,3H),3.75(t,J=5.6Hz,2H),3.08(t,J=6.4Hz,2H),2.14-1.87(m,3H). 13 C NMR (100MHz, Chloroform-d) δ199.3,163.7,130.5,130.1,113.9,62.6,55.6,35.2,27.3.

[0176]

[0177] Sec-butyl 2-(2-((4-(4-methoxyphenyl)-4-oxobutanoyl)oxy)ethyl)piperidine-1-carboxylate(16)

[0178] Appearance: Brown oily liquid. 1 H NMR(400MHz,Chloroform-d)δ7.96-7.94(m,2H),6.93-6.91(m,2H),4.77-4.69 (m,1H),4.39(s,1H),4.12-4.03(m,2H),3.85(s,3H),3.25(t,J=6.8Hz,2H),2. 84-2.73(m,1H),2.72(t,J=6.8Hz,2H),2.13-2.00(m,1H),1.78-1.68(m,1H),1 .64-1.49(m,8H),1.44-1.34(m,1H),1.18(d,J=6.4Hz,3H),0.92-0.84(m,3H). 13 CNMR(100MHz,Chloroform-d)δ196.7,173.1,163.7,155.6,130.4,129.8,113.9,73.0,62.5,5 5.6,48.0,39.0,33.1,29.2,28.9,28.8,28.5,25.6,19.9,19.2,9.9.HR-MS(ESI)m / zcalc.for C 23 H 34 NO6[M+H] + :420.2386,found:420.2390.

[0179]

[0180] (3S,5S,8R,9S,10S,13S,14S)-10,13-Dimethyl-17-oxohexadecahydro-1H-cyclopenta[a]phenanthr en-3-yl 4-(4-methoxyphenyl)-4-oxobutanoate(17)

[0181] Appearance: White solid. MPa: 145-146℃. 11H NMR (400 MHz, Chloroform-d) δ 7.97 - 7.95 (m, 2H), 6.94 - 6.91 (m, 2H), 4.75 - 4.66 (m, 1H), 3.86 (s, 3H), 3.24 (t, J = 6.4 Hz, 2H), 2.70 (t, J = 6.4 Hz, 2H), 2.42 (dd, J = 19.2, 8.8 Hz, 1H), 2.05 (dt, J = 18.4, 8.8 Hz, 1H), 1.95 - 1.88 (m, 1H), 1.84 - 1.69 (m, 4H), 1.67 - 1.59 (m, 2H), 1.55 - 1.45 (m, 3H), 1.38 - 1.12 (m, 7H), 1.05 - 0.94 (m, 2H), 0.84 (d, J = 4.4 Hz, 6H), 0.73 - 0.66 (m, 1H). 13 13C NMR (100 MHz, Chloroform-d) δ 221.4, 196.9, 172.7, 163.6, 130.4, 129.9, 113.8, 73.9, 55.6, 54.4, 51.5, 47.9, 44.8, 36.8, 36.0, 35.8, 35.1, 34.0, 33.2, 31.6, 30.9, 28.9, 28.4, 27.5, 21.9, 20.6, 13.9, 12.3. HR-MS (ESI) m / z calc. for C 30 1 41 25H39O5 [M + H] + : 481.2954, found: 481.2959.

[0182]

[0183] (1R,2R,4S)-1,7,7-Trimethylbicyclo[2.2.1]heptan-2-yl 4-(4-methoxyphenyl)-4-oxobutanoate (18)

[0184] Appearance: White solid. M.p.: 42 - 43 °C. 1HNMR(400MHz,Chloroform-d)δ7.96-7.94(m,2H),6.94-6.91(m,2H),4.68-4.65(m,1H),3.86(s,3H),3.24(t,J=6.8Hz, 2H),2.72(t,J=6.8Hz,2H),1.81-1.64(m,4H),1.56-1.49(m,1H),1.17-1.03(m,2H),0.94(s,3H),0.82(d,J=7.2Hz,6H). 13 C NMR(100MHz,Chloroform-d)δ196.7,172.5,163.6,130.4,129.9,113.8,81.4,55. 6,48.8,47.0,45.1,38.9,33.9,33.2,28.9,27.2,20.2,20.0,11.6.HR-MS(ESI)m / z calc.for C 21 H 28 O4Na[M+Na] + :367.1886,found:367.1886.

[0185]

[0186] 1,3,3-Trimethylbicyclo[2.2.1]heptan-2-yl 4-(4-methoxyphenyl)-4-oxobutanoate(19)

[0187] Appearance: Colorless oily liquid. 1 H NMR(400MHz,Chloroform-d)δ7.98-7.95(m,2H),6.94-6.92(m,2H),4.37(s,1H),3.87(s,3H),3.27(t,J=6.8Hz,2H),2.7 9(t,J=6.8Hz,2H),1.75-1.64(m,3H),1.59-1.53(m,1H),1.46-1.38(m,1H),1.18–1.16(m,1H),1.06(m,7H),0.79(s,3H). 13CNMR (100 MHz, Chloroform-d) δ 196.7, 173.5, 163.6, 130.4, 129.9, 113.9, 86.5, 55.6, 48.5, 48.4, 41.5, 39.6, 33.2, 29.8, 28.5, 26.7, 25.9, 20.3, 19.5. HR-MS (ESI) m / z calc. for C 21 H 29 O4 [M + H] + : 345.2066, found: 345.2066.

[0188]

[0189] 2-Isopropyl-5-methylcyclohexyl 4-(4-methoxyphenyl)-4-oxobutanoate (20)

[0190] Appearance: White solid. M.p.: 63 - 64 °C. 1 HNMR (400 MHz, Chloroform-d) δ 7.97 - 7.95 (m, 2H), 6.94 - 6.92 (m, 2H), 4.73 - 4.66 (m, 1H), 3.86 (s, 3H), 3.28 - 3.23 (t, J = 6.8 Hz, 2H), 2.73 (t, J = 6.8 Hz, 2H), 2.03 - 1.97 (m, 1H), 1.92 - 1.83 (m, 1H), 1.69 - 1.61 (m, 2H), 1.52 - 1.41 (m, 1H), 1.40 - 1.32 (m, 1H), 1.08 - 0.96 (m, 2H), 0.93 - 0.85 (m, 7H), 0.76 (d, J = 6.8 Hz, 3H). 13 CNMR (100 MHz, Chloroform-d) δ 196.8, 172.7, 163.6, 130.4, 129.9, 113.8, 74.6, 55.6, 47.1, 41.0, 34.4, 33.2, 31.5, 28.9, 26.4, 23.6, 22.2, 20.9, 16.5. HR-MS (ESI) m / z calc. for C 21 H 30 O4Na [M + Na] + : 369.2042, found: 369.2042.

[0191]

[0192] Methyl 4-([1,1'-biphenyl]-4-yl)-4-oxobutanoate(21)

[0193] Appearance: White solid. MPa: 10³-10⁴℃. 1 H NMR(400MHz,Chloroform-d)δ8.11-8.01(m,2H),7.72-7.66(m,2H),7.66-7.60(m,2H),7.51 -7.44(m,2H),7.44-7.37(m,1H),3.72(s,3H),3.36(t,J=6.4Hz,2H),2.80(t,J=6.4Hz,2H). 13 C NMR(100MHz,Chloroform-d)δ197.8,173.5,146.0,140.0,135.3,129.1,128.8,128.4,127.4,52.0,33.6,28.2.HR-MS(ESI)m / z calc.for C 17 H 17 O3[M+H] + :269.1178,found:269.1182.

[0194]

[0195] 4-(4-Methoxyphenyl)-4-oxobutyl acetyl-L-isoleucinate(22)

[0196] Appearance: Colorless oily liquid. dr = 13:7. 1 H NMR(400MHz,Chloroform-d)δ7.95-7.93(m,2H),6.95-6.92(m,2H),[6.00(d,J=8.8Hz),5 .93(J=8.8Hz),1H],[4.69(dd,J=9.0,4.2Hz),4.59(J=8.6,5.0Hz),1H],4.23(t,J=6.4Hz, 2H),3.87(s,3H),3.04-2.99(m,2H),2.14-2.07(m,2H),2.02(d,J=2.8Hz,3H),1.93-1.82( m,1H),1.46-1.37(m,1H),1.20-1.11(m,1H),0.91(q,J=7.2Hz,4H),0.85(d,J=6.8Hz,2H). 1313C NMR (100 MHz, Chloroform-d) δ 197.6, 172.6, 172.3, 170.2, 169.9, 163.7, 130.4, 130.0, 113.9, 64.9, 64.8, 56.6, 55.6, 55.6, 38.2, 37.9, 34.4, 26.3, 25.4, 23.4, 23.4, 23.3, 15.5, 14.8, 11.9, 11.8. HR-MS (ESI) m / z calc. for C 19 H 27 NO5Na [M+Na] + : 372.1787, found: 372.1790.

[0197]

[0198] 4-(4-Methoxyphenyl)-4-oxobutyl (S)-5-oxopyrrolidine-2-carboxylate (23)

[0199] Appearance: White solid. M.p.: 62 - 63 °C. 1 1H NMR (400 MHz, Chloroform-d) δ 7.94 - 7.92 (m, 2H), 6.94 - 6.92 (m, 2H), 6.36 (s, 1H), 4.28 - 4.19 (m, 3H), 3.86 (s, 3H), 3.01 (t, J = 7.2 Hz, 2H), 2.48 - 2.40 (m, 1H), 2.38 - 2.27 (m, 2H), 2.25 - 2.16 (m, 1H), 2.15 - 2.09 (m, 2H). 13 13C NMR (100 MHz, Chloroform-d) δ 197.4, 177.9, 172.0, 163.6, 130.3, 129.7, 113.8, 65.2, 55.5, 55.4, 34.3, 29.2, 24.8, 23.2. HR-MS (ESI) m / z calc. for C 16 H 20 NO5 [M+H] + : 306.1341, found: 306.1330.

[0200]

[0201] 1-(Tert-butyl) 2-(4-(4-methoxyphenyl)-4-oxobutyl) (S)-pyrrolidine-1,2-dicarboxylate (24)

[0202] Appearance: Colorless oily liquid. 1 H NMR(400MHz,Chloroform-d)δ7.96-7.91(m,2H),6.94-6.90(m,2H),4.32-4.16(m,3H),3.86-3.85(m,3H),3.56-3.34(m,2H ),3.05-2.97(m,2H),2.26-2.13(m,1H),2.11-2.02(m,2H),1.97-1.80(m,3H),1.43-1.38(m,9H).HR-MS(ESI)m / zcalc.for C 21 H 30 NO6[M+H] + :392.2073,found:392.2074.

[0203]

[0204] 4-(4-Methoxyphenyl)-4-oxobutyl(tert-butoxycarbonyl)-L-valinate(25)

[0205] Appearance: Colorless oily liquid. 1 H NMR(400MHz,Chloroform-d)δ7.94-7.92(m,2H),6.93-6.91(m,2H),5.02(d,J=8.8Hz,1H),4.23(m,3 H),3.86(s,3H),3.01(m,2H),2.10(m,3H),1.42(s,9H),0.95(d,J=6.8Hz,3H),0.87(d,J=6.8Hz,3H). 13 C NMR(100MHz,Chloroform-d)δ197.5,172.5,163.5,155.7,130.3,129.8,113.8,79.7,64.5,58.6,55.5,34.3,31.3,28.3,23.3,19.0,17.6.HR-MS(ESI)m / z calc.for C 21 H 31 NO6Na[M+Na] + :416.2049,found:416.2047.

[0206]

[0207] 4-(4-Methoxyphenyl)-4-oxobutyl(tert-butoxycarbonyl)glycinate(26)

[0208] Appearance: Colorless oily liquid. 1 H NMR(400MHz,Chloroform-d)δ7.93-7.91(m,2H),6.93-6.91(m,2H),5.05(s,1H),4.23(t ,J=6.4Hz,2H),3.88-3.85(m,5H),3.00(t,J=6.8Hz,2H),2.12–2.05(m,2H),1.43(s,9H). 13 C NMR(100MHz,Chloroform-d)δ197.5,170.4,163.5,155.7,130.3,129.8,113.8,80.0,64.7,55.5,42.4,34.3,28.3,23.2.HR-MS(ESI)m / zcalc.for C 18 H 25 NO6Na[M+Na] + :374.1580,found:374.1574.

[0209]

[0210] 4-(4-Methoxyphenyl)-4-oxobutyl(tert-butoxycarbonyl)-D-asparaginate(27)

[0211] Appearance: Colorless oily liquid. 1 H NMR(400MHz,Chloroform-d)δ7.94-7.92(m,2H),6.92-6.90(m,2H),5.53–5.52(m,1H),4.50–4.45(m,1H),4 .32(t,J=6.2Hz,2H),3.84(s,3H),3.03(t,J=7.2Hz,2H),3.00-2.84(m,2H),2.16-2.09(m,2H),1.43(s,9H). 13 C NMR (100MHz, Chloroform-d) δ197.3,169.0,163.6,154.9,130.3,129.7,116.4,113.8,80.9,66.2,55.5,50.4,34.2,28.2,23.0,21.7.HR-MS(ESI)m / z calc.for C20 H 29 N₂O₇[M+H] + :409.1975,found:409.1960.

[0212]

[0213] 4-(4-Methoxyphenyl)-4-oxobutyl 2-(2,4-dichlorophenoxy)acetate(28)

[0214] Appearance: White solid. Mp: 95-96℃. 1 HNMR(400MHz,Chloroform-d)δ7.90-7.88(m,2H),7.36-7.35(m,1H),7.14-7.12(m,1H),6.94-6.92(m,2H),6 .77-6.75(m,1H),4.67(s,2H),4.30(t,J=6.4Hz,2H),3.87(s,3H),2.95(t,J=6.8Hz,2H),2.15-2.03(m,2H). 13 C NMR(100MHz,Chloroform-d)δ197.3,168.1,163.6,152.4,130.4,130.2,129.8, 127.6,127.1,124.2,114.6,113.8,66.4,65.0,55.5,34.2,23.1.HR-MS(ESI)m / z calc.for C 19 H 19 Cl2O5[M+H] + :397.0609,found:397.0595.

[0215]

[0216] 4-(4-Methoxyphenyl)-4-oxobutyl stearate(29)

[0217] Appearance: White solid. MPa: 54-55℃. 1HNMR(400MHz, Chloroform-d) δ 7.95 - 7.93 (m, 2H), 6.94 - 6.92 (m, 2H), 4.16 (t, J = 6.4Hz, 2H), 3.87 (s, 3H), 3.00 (t, J = 7.2Hz, 2H), 2.28 (t, J = 7.6Hz, 2H), 2.12 - 2.04 (m, 2H), 1.63 - 1.57 (m, 2H), 1.31 - 1.22 (m, 28H), 0.87 (t, J = 6.4Hz, 3H). 13 C NMR(100MHz, Chloroform-d) δ 197.7, 173.9, 163.5, 130.3, 130.0, 113.7, 63.6, 55.5, 34.5, 34.3, 31.9, 29.7, 29.7, 29.6, 29.5, 29.4, 29.3, 29.2, 25.0, 23.4, 22.7, 14.1. HR-MS(ESI) m / z calc. for C 29 H 49 O4[M + H] + : 461.3631, found: 461.3616. [[ID=1~13]]

[0218]

[0219]

[0220] Methyl 4'-hexanoyl-[1,1'-biphenyl]-4-carboxylate(30)[[ID=15~16]]

[0220] Appearance: White solid. M.p.: 152 - 153 °C.<UNK>0000115H NMR(400MHz, Chloroform-d) δ 8.13 - 8.14 (m, 4H), 7.71 - 7.67 (m, 4H), 3.94 (s, 3H), 2.99 (t, J = 7.2Hz, 2H), 1.80–1.73 (m, 2H), 1.40 - 1.36 (m, 4H), 0.98 - 0.87 (m, 3H). 13 C NMR(100MHz, Chloroform-d) δ 200.0, 166.8, 144.3, 144.2, 136.5, 130.2, 129.7, 128.7, 127.4, 127.2, 52.2, 38.7, 31.6, <UNK>24.1, 22.6, 14.0. HR-MS(ESI) m / z calc. for C 20 H 22 O3Na[M + Na][[ID= <UNK>26]] + : 333.1467, found: 333.1453. ​​​​

[0221]

[0222] Fenofibrate(31)

[0223] Appearance: White solid. Mp: 82-83℃. 1 HNMR(400MHz,Chloroform-d)δ7.72-7.66(m,4H),7.42-7.40(m,2H),6.85-6.83(m,2H),5.10-5.04(m,1H),1.64(s,6H),1.18(d,J=6.0Hz,6H). 13 CNMR(100MHz,Chloroform-d)δ194.2,173.1,159.7,138.3,136.4,132.0,131.2,130.2,128.5,117.2,79.4,69.3,25.4,21.5.

[0224]

[0225] Fenbufen(32)

[0226] Appearance: White solid. MPa: 186-187℃. 1 H NMR(400MHz,DMSO-d6)δ12.21(s,1H),8.10-8.00(m,2H),7.84-7.75(m,2H),7.75-7.66(m ,2H),7.51-7.47(m,2H),7.45-7.38(m,1H),3.27(t,J=6.4Hz,2H),2.63(t,J=6.4Hz,2H). 13 C NMR (100MHz, Chloroform-d) δ203.2,179.1,149.7,144.1,140.5,134.3,133.8,133.6,132.2,132.1,45.1,44.9,44.7,44.5,44.3,38.4,33.1.

[0227]

[0228] Oxcarbazepine(33)

[0229] Appearance: White solid. MPa: 215-216℃. 1H NMR(400MHz,Chloroform-d)δ8.11–8.10(m,1H),7.68–7.66(m,1H),7.61-7.57(m,1H),7.53-7.47 (m,1H),7.44-7.38(m,1H),7.38-7.30(m,3H),4.95(s,2H),4.47–4.44(m,1H),3.87–3.83(m,1H). 13 C NMR (100MHz, Chloroform-d) δ191.9,155.9,143.1,141.3,134.0,134.0,130.7,130.3,129.9,129.4,129.1,128.7,127.8,127.4,49.1.

[0230]

[0231] 1-(4-Iodophenyl)ethan-1-one(34)

[0232] Appearance: Brown solid. Mp: 82-84℃. 1 H NMR (400MHz, Chloroform-d) δ7.84–7.82(m,2H),7.67–7.65(m,2H),2.57(s,3H). 13 C NMR (100MHz, Chloroform-d) δ197.4,137.9,136.4,129.7,101.1,26.5.

[0233]

[0234] 1-(4-Bromophenyl)ethan-1-one(35)

[0235] Appearance: Yellow solid. MPa: 109-110℃. 1 H NMR (400MHz, Chloroform-d) δ7.83–7.81(m,2H),7.61–7.59(m,2H),2.58(s,3H). 13 C NMR (100MHz, Chloroform-d) δ197.0,135.8,131.9,129.9,128.3,26.6.

[0236]

[0237] 1-(4-Chlorophenyl)ethan-1-one(36)

[0238] Appearance: Colorless oily liquid. 1 H NMR (400MHz, Chloroform-d) δ7.89–7.87(m,2H),7.43–7.41(m,2H),2.58(s,3H). 13 C NMR (100MHz, Chloroform-d) δ196.8,139.6,135.4,129.7,128.9,26.6.

[0239]

[0240] 1-(4-Fluorophenyl)ethan-1-one(37)

[0241] Appearance: Colorless oily liquid. 1 H NMR (400MHz, Chloroform-d) δ7.95-7.92(m,2H),7.10-7.05(m,2H),2.54(s,3H). 13 C NMR(100MHz,Chloroform-d)δ196.4,167.0,164.5(d,J C-F =244.0Hz), 133.6, 133.5 (d, J) C-F =3.0Hz), 131.0, 130.9(d,J) C-F =9.0Hz), 115.7, 115.5 (d, J) C-F =21.0Hz), 26.5. 19 F NMR(375MHz,Chloroform-d)δ-105.4.

[0242]

[0243] 1-(4-Methoxyphenyl)ethan-1-one(38)

[0244] Appearance: Colorless oily liquid. 1 H NMR (400MHz, Chloroform-d) δ7.95–7.93(m,2H),6.94–6.92(m,2H),3.87(s,3H),2.56(s,3H). 13 C NMR (100MHz, Chloroform-d) δ196.8,163.5,130.6,130.4,113.7,55.5,26.4.

[0245]

[0246] 1-(4-Methoxyphenyl)propan-1-one(39)

[0247] Appearance: Colorless oily liquid. 1 H NMR (400MHz, Chloroform-d) δ7.95–7.93(m,2H),6.93–6.91(m,2H),3.85(s,3H),2.94(q,J=7.2Hz,2H),1.20(t,J=7.2Hz,3H). 13 C NMR (100MHz, Chloroform-d) δ199.5,163.3,130.2,130.0,113.7,55.4,31.4,8.4.

[0248]

[0249] 1-(2-Methoxyphenyl)ethan-1-one(40)

[0250] Appearance: Colorless oily liquid. 1 H NMR (400MHz, Chloroform-d) δ7.75-7.72(m,1H),7.49-7.44(m,1H),7.05-6.93(m,2H),3.91(s,3H),2.61(s,3H). 13 C NMR (100MHz, Chloroform-d) δ199.9,158.9,133.7,130.4,128.3,120.6,111.6,55.5,31.9.

[0251]

[0252] 1-(4-Phenoxyphenyl)ethan-1-one(41)

[0253] Appearance: White solid. MPa: 51-52℃. 1 H NMR (400MHz, Chloroform-d) δ7.95–7.93(m,2H),7.46-7.33(m,2H),7.23-7.15(m,1H),7.08–7.06(m,2H),7.01–6.99(m,2H),2.57(s,3H). 13C NMR (100MHz, Chloroform-d) δ196.7,162.0,155.5,131.9,130.6,130.1,124.6,120.2,117.3,26.5.

[0254]

[0255] 1-(4-Isopropylphenyl)ethan-1-one(42)

[0256] Appearance: Colorless oily liquid. 1 H NMR (400MHz, Chloroform-d) δ7.91–7.89(m,2H),7.32–7.30(m,2H),3.00-2.93(m,1H),2.58(s,3H),1.27(d,J=7.2Hz,6H). 13 C NMR (100MHz, Chloroform-d) δ197.9,154.6,135.0,128.6,126.6,34.2,26.5,23.7.

[0257]

[0258] 1-(4-(Tert-butyl)phenyl)ethan-1-one(43)

[0259] Appearance: Colorless oily liquid. 1 H NMR (400MHz, Chloroform-d) δ7.94–7.92(m,2H),7.52–7.50(m,2H),2.61(s,3H),1.37(s,9H). 13 C NMR (100MHz, Chloroform-d) δ197.9,156.8,134.6,128.3,125.5,35.1,31.1,26.6.

[0260]

[0261] 4-Acetylphenyl acetate (44)

[0262] Appearance: White solid. MPa: 50-51℃. 1 HNMR(400MHz,Chloroform-d)δ8.02-7.95(m,2H),7.24-7.13(m,2H),2.59(s,3H),2.32(s,3H). 13C NMR (100MHz, Chloroform-d) δ196.9,168.9,154.4,130.0,121.8,26.6,21.2.

[0263]

[0264] 1-(3,4-Dimethoxyphenyl)ethan-1-one(45)

[0265] Appearance: Yellow solid. MPa: 50-51℃. 1 H NMR (400MHz, Chloroform-d) δ7.59-7.56(m,1H),7.53–7.52(m,1H),6.89–6.87(m,1H),3.94(s,3H),3.93(s,3H),2.56(s,3H). 13 C NMR (100MHz, Chloroform-d) δ196.8,153.3,149.0,130.5,123.3,110.1,109.9,56.1,56.0,26.2.

[0266]

[0267] 4-Acetylbenzonitrile(46)

[0268] Appearance: Yellow solid. MPa: 58-59℃. 1 H NMR (400MHz, Chloroform-d) δ8.05–8.03(m,2H),7.79–7.77(m,2H),2.64(s,3H). 13 C NMR (100MHz, Chloroform-d) δ196.6,139.9,132.6,128.7,118.0,116.4,26.8.

[0269]

[0270] Methyl 4-acetylbenzoate (47)

[0271] Appearance: White solid. Mp: 95-96℃. 1 H NMR (400MHz, Chloroform-d) δ8.13–8.10(m,2H),8.01–7.99(m,2H),3.94(s,3H),2.64(s,3H). 13C NMR (100MHz, Chloroform-d) δ197.6,166.2,140.2,133.9,129.8,128.2,52.5,26.9.

[0272]

[0273] 1-([1,1'-Biphenyl]-4-yl)ethan-1-one(48)

[0274] Appearance: White solid. MPa: 153-154℃. 1 H NMR (400MHz, Chloroform-d) δ8.09-7.97(m,2H),7.75-7.66(m,2H),7.64–7.63(m,2H),7.52-7.44(m,2H),7.44-7.38(m,1H),2.64(s,3H). 13 CNMR(100MHz,Chloroform-d)δ197.8,145.8,139.9,135.9,129.0,128.9,128.3,127.3,127.2,26.7.

[0275]

[0276] 1-(4'-Bromo-[1,1'-biphenyl]-4-yl)ethan-1-one(49)

[0277] Appearance: White solid. MPa: 130-131℃. 1 H NMR (400MHz, Chloroform-d) δ8.06-8.00(m,2H),7.67-7.62(m,2H),7.61-7.56(m,2H),7.51-7.46(m,2H),2.64(s,3H). 13 C NMR (100MHz, Chloroform-d) δ197.7,144.5,138.8,136.1,132.1,129.0,128.9,127.1,122.7,26.8.

[0278]

[0279] 4'-Acetyl-[1,1'-biphenyl]-4-carbonitrile(50)

[0280] Appearance: Colorless oily liquid. 1H NMR (400MHz, Chloroform-d) δ8.09-8.04(m,2H),7.79-7.74(m,2H),7.74-7.71(m,2H),7.70-7.67(m,2H),2.65(s,3H). 13 C NMR (100MHz, Chloroform-d) δ197.5,144.3,143.6,136.9,132.8,129.1,128.0,127.5,118.7,111.9,26.8.

[0281]

[0282] 1-([1,1'-Biphenyl]-4-yl)butan-1-one(51)

[0283] Appearance: White solid. MPa: 57-58℃. 1 H NMR(400MHz,Chloroform-d)δ8.05–8.03(m,2H),7.72-7.66(m,2H),7.65-7.62(m,2H),7.51-7 .45(m,2H),7.44-7.37(m,1H),2.99(t,J=7.2Hz,2H),1.85-1.76(m,2H),1.03(t,J=7.2Hz,3H). 13 C NMR (100MHz, Chloroform-d) δ200.2,145.7,140.1,135.9,129.1,128.8,128.3,127.4,40.7,18.0,14.0.

[0284]

[0285] 3-(4-(Tert-butyl)phenyl)-1-(4-methoxyphenyl)propan-1-one(52)

[0286] Appearance: White solid. Mp: 72-73℃. 1 H NMR(400MHz,Chloroform-d)δ7.95–7.93(m,2H),7.33–7.31(m,2H),7.20–7.18(m,2H),6 .93–6.90(m,2H),3.85(s,3H),3.24(t,J=8.0Hz,2H),3.02(t,J=8.0Hz,2H),1.31(s,9H). 13C NMR (100MHz, Chloroform-d) δ198.1,163.5,149.0,138.5,130.4,130.1,128.2,125.5,113.8,55.5,40.3,34.5,31.5,29.9.

[0287]

[0288] (4-Bromophenyl)(cyclopropyl)methanone(53)

[0289] Appearance: Colorless oily liquid. 1 H NMR (400MHz, Chloroform-d) δ7.88–7.86(m,2H),7.61–7.59(m,2H),2.63-2.57(m,1H),1.26-1.22(m,2H),1.07-1.03(m,2H). 13 C NMR (100MHz, Chloroform-d) δ199.6,136.7,131.8,129.6,127.8,17.1,11.9.

[0290]

[0291] 5-(Tert-butyl)-7-ethyl-3,3-dimethyl-2,3-dihydro-1H-inden-1-one(54)

[0292] Appearance: Yellow oily liquid. 1 H NMR(400MHz,Chloroform-d)δ7.30(d,J=1.6Hz,1H),7.18(d,J=1.6Hz,1H),3.06 (q,J=7.6Hz,2H),2.55(s,2H),1.40(s,6H),1.36(s,9H),1.24(t,J=7.2Hz,3H). 13 C NMR(100MHz,Chloroform-d)δ206.0,165.2,158.6,144.4,130.0,125.2,117.4,54.0,37.8,35.6,31.4,30.3,25.3,15.2.HR-MS(ESI)m / z calc.forC 17 H 24 ONa[M+Na] + :267.1725,found:267.1721.

[0293]

[0294] 2,3-Dihydro-1H-inden-1-one(55)

[0295] Appearance: Colorless oily liquid. 1 H NMR (400MHz, Chloroform-d) δ7.77-7.73(m,1H),7.53-7.47(m,1H),7.42-7.37(m,1H),7.32-7.25(m,1H),3.07(t,J=6.0Hz,2H),2.68(t,J=6.0Hz,2H). 13 C NMR (100MHz, Chloroform-d) δ207.2,155.3,137.2,134.7,127.4,126.8,123.8,36.3,25.9.

[0296]

[0297] 3,4-Dihydronaphthalen-1(2H)-one(56)

[0298] Appearance: Colorless oily liquid. 1 H NMR(400MHz,Chloroform-d)δ7.97–7.96(m,1H),7.42-7.38(m,1H),7.25-7.22(m,1H) ),7.19–7.17(m,1H),2.90(t,J=6.0Hz,2H),2.59(t,J=6.4Hz,2H),2.10-2.04(m,2H). 13 C NMR (100MHz, Chloroform-d) δ198.6,144.6,133.5,132.8,128.9,127.3,126.8,39.3,29.9,23.4.

[0299]

[0300] 6-Methoxy-3,4-dihydronaphthalen-1(2H)-one(57)

[0301] Appearance: Yellow solid. MPa: 78-79℃. 1H NMR(400MHz,Chloroform-d)δ8.01–8.00(m,1H),6.83-6.80(m,1H),6.70–6.69(m ,1H),3.85(s,3H),2.92(t,J=6.0Hz,2H),2.60(t,J=6.4,2H),2.14-2.07(m,2H). 13 C NMR (100MHz, Chloroform-d) δ197.4,163.6,147.1,129.7,126.4,113.1,112.7,55.5,39.0,30.3,23.5.

[0302]

[0303] Chroman-4-one(58)

[0304] Appearance: Colorless oily liquid. 1 H NMR (400MHz, Chloroform-d) δ7.90-7.88(m,1H),7.49-7.45(m,1H),7.03-6.96(m,2H),4.54(t,J=6.4Hz,2H),2.81(t,J=6.4Hz,2H). 13 C NMR (100MHz, Chloroform-d) δ192.0,162.0,136.1,127.3,121.5,121.5,118.0,67.1,37.9.

[0305]

[0306] (4-Iodophenyl)(phenyl)methanone(59)

[0307] Appearance: White solid. Mp: 98-99℃. 1 HNMR(400MHz,Chloroform-d)δ7.89-7.81(m,2H),7.80-7.74(m,2H),7.63-7.57(m,1H),7.55-7.46(m,4H). 13 C NMR (100MHz, Chloroform-d) δ196.0,137.8,137.2,137.0,132.8,131.6,130.1,128.5,100.3.

[0308]

[0309] (4-Bromophenyl)(phenyl)methanone(60)

[0310] Appearance: White solid. Mp: 81-82℃. 1 HNMR(400MHz,Chloroform-d)δ7.86-7.73(m,2H),7.71-7.65(m,2H),7.65-7.56(m,3H),7.51-7.47(m,2H). 13 C NMR (100MHz, Chloroform-d) δ195.7,137.3,136.4,132.8,131.7,131.7,130.1,128.5,127.6.

[0311]

[0312] (4-Chlorophenyl)(phenyl)methanone(61)

[0313] Appearance: White solid. MPa: 75-76℃. 1 HNMR(400MHz,Chloroform-d)δ7.78-7.74(m,4H),7.62-7.58(m,1H),7.53-7.42(m,4H). 13 C NMR (100MHz, Chloroform-d) δ195.6,139.0,137.4,136.0,132.8,131.6,130.1,128.8,128.5.

[0314]

[0315] Bis(4-fluorophenyl)methanone(62)

[0316] Appearance: White solid. Mp: 62-63℃. 1 HNMR(400MHz,Chloroform-d)δ7.83-7.80(m,4H),7.19-7.15(m,4H). 13 C NMR(100MHz,Chloroform-d)δ193.9,166.8,164.2(d,J C-F =253.0Hz), 133.8, 133.8(d,J) C-F =3.0Hz), 132.7, 132.6 (d, J) C-F =9.0Hz), 115.8, 115.6 (d, J)C-F =21.0Hz). 19 F NMR(375MHz,Chloroform-d)δ-105.7.

[0317]

[0318] Phenyl(p-tolyl)methanone(63)

[0319] Appearance: White solid. MPa: 56-57℃. 1 H NMR (400MHz, Chloroform-d) δ7.79–7.78(m,2H),7.74–7.72(m,2H),7.60-7.56(m,1H),7.49-7.46(m,2H),7.29–7.28(m,2H),2.44(s,3H). 13 C NMR (100MHz, Chloroform-d) δ196.7,143.4,138.1,135.0,132.3,130.5,130.1,129.1,128.4,21.8.

[0320]

[0321] (4-Methoxyphenyl)(phenyl)methanone(64)

[0322] Appearance: White solid. Mp: 62-63℃. 1 HNMR(400MHz,Chloroform-d)δ7.88-7.79(m,2H),7.79-7.70(m,2H),7.60-7.53(m,1H),7.51-7.42(m,2H),6.98–6.95(m,2H),3.89(s,3H). 13 CNMR(100MHz,Chloroform-d)δ195.7,163.3,138.4,132.7,132.0,130.3,129.8,128.3,113.7,55.6.

[0323]

[0324] Phenyl(4-(trifluoromethoxy)phenyl)methanone(65)

[0325] Appearance: Colorless oily liquid. 1H NMR (400MHz, Chloroform-d) δ7.90-7.84(m,2H),7.82-7.75(m,2H),7.64-7.58(m,1H),7.52-7.48(m,2H),7.32–7.31(m,2H). 13 C NMR(100MHz,Chloroform-d)δ195.3,152.3,152.2(d,J C-F =2.0Hz),137.2,136.0,132.8,132.1,130.1,128.6,121.7,120.3,119.2(d,J C-F =257.0Hz). 19 F NMR(375MHz,Chloroform-d)δ-57.6.

[0326]

[0327] (4-Isopropylphenyl)(phenyl)methanone(66)

[0328] Appearance: Colorless oily liquid. 1 H NMR(400MHz,Chloroform-d)δ7.84-7.78(m,2H),7.78-7.73(m,2H),7.61-7.54( m,1H),7.52-7.43(m,2H),7.34(m,2H),3.03-2.96(m,1H),1.30(d,J=6.8Hz,6H). 13 C NMR (100MHz, Chloroform-d) δ196.7,154.1,138.1,135.4,132.3,130.5,130.1,128.3,126.5,34.5,23.8.

[0329]

[0330] (4-(Tert-butyl)phenyl)(phenyl)methanone(67)

[0331] Appearance: Colorless oily liquid. 1 H NMR (400MHz, Chloroform-d) δ7.82-7.76(m,4H),7.60-7.56(m,1H),7.54-7.45(m,4H),1.37(s,9H). 13C NMR (100MHz, Chloroform-d) δ196.5,156.2,138.0,134.8,132.2,130.2,130.0,128.2,125.3,35.1,31.2.

[0332]

[0333] [1,1'-Biphenyl]-4-yl(phenyl)methanone(68)

[0334] Appearance: White solid. Mp: 100-101℃. 1 H NMR(400MHz,Chloroform-d)δ7.92-7.90(m,2H),7.87-7.84(m,2H),7.75-7.69(m ,2H),7.68-7.65(m,2H),7.63-7.57(m,1H),7.56-7.45(m,4H),7.45-7.38(m,1H). 13 C NMR (100MHz, Chloroform-d) δ196.5,145.4,140.1,137.9,136.4,132.5,130.9,130.1,129.1,128.4,128.3,127.4,127.1.

[0335]

[0336] Methyl 4-benzoylbenzoate (69)

[0337] Appearance: White solid. MPa: 10⁶-10⁷℃. 1 H NMR (400MHz, Chloroform-d) δ8.16–8.14(m,2H),7.87-7.83(m,2H),7.82-7.77(m,2H),7.65-7.59(m,1H),7.53-7.47(m,2H),3.97(s,3H). 13 C NMR (100MHz, Chloroform-d) δ196.2,166.5,141.5,137.1,133.4,133.1,130.3,129.9,129.7,128.6,52.7.

[0338]

[0339] Benzophenone (70)

[0340] Appearance: White solid. MPa: 48-49℃. 1 HNMR(400MHz,Chloroform-d)δ7.82–7.80(m,4H),7.63-7.56(m,2H),7.50-7.46(m,4H). 13 C NMR(100MHz,Chloroform-d)δ196.8,137.6,132.5,130.1,128.3.

[0341]

[0342] Phenyl(thiophen-2-yl)methanone(71)

[0343] Appearance: White solid. Mp: 57-58℃. 1 H NMR (400MHz, Chloroform-d) δ7.88–7.86(m,2H),7.73–7.72(m,1H),7.66–7.65(m,1H),7.61-7.58(m,1H),7.52-7.48(m,2H),7.18-7.16(m,1H). 13 C NMR (100MHz, Chloroform-d) δ188.4,143.8,138.2,135.0,134.4,132.4,129.3,128.6,128.1.

[0344]

[0345] 9H-Xanthen-9-one(72)

[0346] Appearance: White solid. Mp: 173-174℃. 1 H NMR (400MHz, Chloroform-d) δ8.36-8.33(m,2H),7.75-7.70(m,2H),7.50-7.48(m,2H),7.40-7.36(m,2H). 13 C NMR (100MHz, Chloroform-d) δ177.4,156.3,135.0,126.8,124.1,122.0,118.2.

[0347]

[0348] 2,7-Di-tert-butyl-9H-fluoren-9-one(73)

[0349] Appearance: White solid. Mp: 108-109℃. 1 H NMR (400MHz, Chloroform-d) δ7.70-7.69(m,2H),7.49-7.46(m,2H),7.39-7.37(m,2H),1.34(s,18H). 13 C NMR (100MHz, Chloroform-d) δ194.9,152.3,141.9,134.6,131.5,121.6,119.8,35.0,31.20.

[0350]

[0351] Anthraquinone (74)

[0352] Appearance: Yellow solid. MPa: 284-285℃. 1 H NMR (400MHz, Chloroform-d) δ8.35-8.27(m,4H),7.83-7.78(m,4H). 13 C NMR(100MHz,Chloroform-d)δ183.3,134.3,133.7,127.4.

[0353]

[0354] 4-(tert-butyl)benzaldehyde(75)

[0355] Appearance: Colorless liquid. 1 H NMR (400MHz, Chloroform-d) δ9.96 (s, 1H), 7.81 (d, J = 8.4Hz, 2H), 7.54 (d, J = 8.4Hz, 2H), 1.34 (s, 9H). 13 C NMR (100MHz, Chloroform-d) δ192.0,158.4,134.1,129.7,126.0,35.4,31.1.

[0356]

[0357] 4-Methoxybenzaldehyde(76)

[0358] Appearance: Colorless liquid. 1H NMR (400MHz, Chloroform-d) δ9.91 (s, 1H), 7.87 (d, J = 8.8Hz, 2H), 7.03 (d, J = 8.8Hz, 2H), 3.92 (s, 3H). 13 C NMR (100MHz, Chloroform-d) δ190.9,164.6,132.0,130.0,114.3,55.6.

[0359] Example 20

[0360] In a 15 mL reaction tube, fixed electrodes were used: anode was carbon felt (GF, 10 mm × 15 mm × 5 mm), and cathode was a platinum sheet (Pt, 10 mm × 15 mm × 0.2 mm). A benzyl-containing compound (0.25 mmol, 1.0 equivalent), KPF6 (46.0 mg, 0.25 mmol, 1.0 equivalent), Ce(OTf)3 (14.7 mg, 0.025 mmol, 10% mol), and a magnetic flux were added to the reaction tube. The tube was then evacuated three times under an Ar atmosphere, and alcohol (250 μL) and acetonitrile (5.0 mL) were added using a syringe. The reaction was carried out at a constant current of 15.0 mA at 40 °C with an Ar balloon for 12 hours. After the reaction was complete, the mixture was evaporated to dryness and concentrated under vacuum. The crude product was purified by column chromatography to obtain the desired product.

[0361] The compounds containing benzyl groups in Example 20 are as follows:

[0362]

[0363] The product prepared in Example 20 is as follows:

[0364]

[0365] Example 21

[0366] In a 15 mL reaction tube, fixed electrodes were used: anode was carbon felt (GF, 10 mm × 15 mm × 5 mm), and cathode was a platinum sheet (Pt, 10 mm × 15 mm × 0.2 mm). A benzyl-containing compound (0.25 mmol, 1.0 equivalent), KPF6 (46.0 mg, 0.25 mmol, 1.0 equivalent), Ce(OTf)3 (14.7 mg, 0.025 mmol, 10% mol), and a magnetic flux were added to the reaction tube. The tube was then evacuated three times under an Ar atmosphere, and alcohol (250 μL) and acetonitrile (5.0 mL) were added using a syringe. The reaction was carried out at a constant current of 15.0 mA at 40 °C with an Ar balloon for 12 hours. After the reaction was complete, the mixture was evaporated to dryness and concentrated under vacuum. The crude product was purified by column chromatography to obtain the desired product.

[0367]

[0368] - Examples 22-36 were modified according to the reaction conditions different from those in Example 21, as shown in Table 2. The changes in reaction conditions and their yields are as follows:

[0369] Table 2

[0370]

[0371]

[0372] The yields in Table 1 above are the yields from the initial NMR spectrum.

[0373] The parameters of the partially carbonylated products synthesized in this invention are as follows:

[0374]

[0375] Methyl 4-methoxybenzoate (77)

[0376] Appearance: White solid. Mp: 49-51℃. 1 H NMR (400MHz, Chloroform-d) δ7.99 (d, J = 8.8 Hz, 2H), 6.92 (d, J = 9.2 Hz, 2H), 3.88 (s, 3H), 3.86 (s, 3H). 13 C NMR (101MHz, Chloroform-d) δ166.9,163.3,131.6,122.6,113.6,55.4,51.8.

[0377]

[0378] Methyl 4-ethoxybenzoate (78)

[0379] Appearance: White solid. Mp: 36-37℃. 1 H NMR (400MHz, Chloroform-d) δ7.98 (d, J = 8.8Hz, 2H), 6.90 (d, J = 8.8Hz, 2H), 4.08 (q, J = 7.2Hz, 2H), 3.88 (s, 3H), 1.43 (t, J = 7.2Hz, 3H). 13 C NMR (100MHz, Chloroform-d) δ166.9,162.8,131.6,122.4,114.1,63.7,51.8,14.7.

[0380]

[0381] Methyl 4-phenoxybenzoate (79)

[0382] Appearance: White solid. Mp: 57-59℃. 1 H NMR (400MHz, Chloroform-d) δ8.01(d,J=8.8Hz,2H),7.43–7.33(m,2H),7.23–7.15(m,1H),7.10–7.02(m,2H),7.02–6.95(m,2H),3.90(s,3H). 13 CNMR(100MHz,Chloroform-d)δ166.6,161.8,155.6,131.7,130.1,124.5,124.5,120.1,117.3,52.0.

[0383]

[0384] Methyl 4-(tert-butyl)benzoate(80)

[0385] Appearance: Colorless oily liquid. 1 H NMR (400MHz, Chloroform-d) δ7.97 (d, J = 8.6 Hz, 2H), 7.45 (d, J = 8.6 Hz, 2H), 3.90 (s, 3H), 1.34 (s, 9H). 13 C NMR (100MHz, Chloroform-d) δ167.1,156.5,129.5,127.4,125.3,51.9,35.1,31.1.

[0386]

[0387] Methyl[1,1'-biphenyl]-4-carboxylate(81)

[0388] Appearance: White solid. Mp: 118-119℃. 1 H NMR (400MHz, Chloroform-d) δ8.15–8.05(m,2H),7.69–7.58(m,4H),7.50–7.43(m,2H),7.43–7.36(m,1H),3.95(s,3H). 13C NMR (100MHz, Chloroform-d) δ167.0,145.6,140.0,130.1,128.9,128.8,128.1,127.2,127.0,52.1.

[0389] Example 37

[0390] The present invention uses aromatic aldehydes / ketones as substrates to synthesize drug molecules containing aromatic carbonyl derivatives, specifically:

[0391]

[0392] Method A in the above figure) Substrate 48 (1.0 equivalent), t BuOK (1.2 equivalents), PPh3CH3Br (2.4 equivalents), ultra-dry THF, 0℃, 1h, then react at room temperature for 5h.

[0393] Method B in the above diagram): The first step of oxidation is carried out under standard conditions, followed by the addition of allyl bromide (3.0 equivalents) and indium powder (3.0 equivalents), at 55°C for 10 hours.

[0394] Method C in the above figure): 48 (1.0 equivalent), NH2OH·HCl (1.5 equivalent), NaOAc (2.6 equivalent), ethanol / water = 1 / 4, 95℃, 10h.

[0395] Method D in the above figure: 48 (1.0 equivalent), NH2NHTs (1.0 equivalent), ultra-dry methanol, 60℃, 1h;

[0396] Method E in the above figure): 48 (1.0 equivalent), NaH (3.0 equivalent), CO(OMe)2 (2.0 equivalent), toluene, reflux, 2h.

[0397] Substrate 48 can be used as a drug molecule containing aromatic aldehyde / ketone derivatives.

[0398] Other aromatic aldehydes / ketones in this invention can also be reacted with corresponding carboxylic acid groups and other compounds. Those skilled in the art can perform the reaction according to their needs.

[0399] The present invention has been described in detail above with reference to specific embodiments and exemplary examples; however, these descriptions should not be construed as limiting the present invention. Those skilled in the art will understand that various equivalent substitutions, modifications, or improvements can be made to the technical solutions and embodiments of the present invention without departing from the spirit and scope of the invention, and all such modifications and improvements fall within the scope of the present invention. The scope of protection of the present invention is defined by the appended claims.

[0400] All publications, patent applications, patents, and other references mentioned in this specification are incorporated herein by reference. Unless otherwise defined, all technical and scientific terms used in this specification have the meanings commonly understood by those skilled in the art. In case of conflict, the definitions in this specification shall prevail.

[0401] When this specification uses the prefixes “known to those skilled in the art,” “prior art,” or similar terms to derive materials, substances, methods, steps, apparatus, or components, the objects derived from such prefixes cover those commonly used in the art at the time of this application, but also include those that are not currently commonly used but will become generally recognized in the art as suitable for similar purposes.

[0402] In the context of this specification, except where expressly stated otherwise, any matters or issues not mentioned shall apply directly to those known in the art without any modification.

Claims

1. A method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction, characterized in that, Includes the following steps: In a protective atmosphere and under electrical conditions, a benzyl-containing compound, an electrolyte, a metal catalyst, water, an alcohol, or an alcohol ether are subjected to an electro-oxidative carbonylation reaction in an organic solvent, followed by post-treatment to obtain the aromatic carbonyl compound. The benzyl-containing compound is selected from at least one of the compounds shown in Formula 1 and Formula 2: ； ； Equation 1; Equation 2; In Equation 1, n≥1; R is alkyl, cycloalkyl, halogen, ketone, hydroxyl, amide, alkoxy, substituted or unsubstituted aryl. R' is selected from hydrogen, unsubstituted alkyl, substituted or unsubstituted alicyclic group, substituted or unsubstituted heterocyclic group; Wherein, R" is selected from substituents containing amide groups, substituents containing NBoc groups, alkyl groups, substituted or unsubstituted aryl groups; R1 is hydrogen, halogen, alkoxy, phenoxy, substituted or unsubstituted aryl, alkyl, cyano, or ester group; R2 is hydrogen or alkoxy; R3 is a hydrogen or alkoxy group; In Equation 2, M is a C4-C6 cycloalkyl group or a C3-C6 heterocyclic group; R4 is hydrogen, alkoxy, or C1-C5 alkyl; R5 is a substituent on ring M, selected from substituted or unsubstituted phenyl or alkyl groups; R6 is hydrogen or a C1-C5 alkyl group; R7 is hydrogen or a C1-C3 alkyl group; The electrolyte is selected from at least one of hexafluorophosphate and tetraalkyl halide; The metal catalyst is selected from at least one of nickel trifluoromethanesulfonate, cobalt trifluoromethanesulfonate, iron trifluoromethanesulfonate, manganese trifluoromethanesulfonate, copper trifluoromethanesulfonate, cerium trifluoromethanesulfonate, and chromium trifluoromethanesulfonate. In the electro-oxidative carbonylation reaction, the cathode material used in the electrode is selected from carbon felt, nickel foam, cobalt, niobium, and platinum sheet; The organic solvent is selected from at least one of amide solvents, nitrile solvents, and sulfoxide solvents.

2. The method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to claim 1, characterized in that: The compound containing a benzyl group is selected from the compounds shown in Formula 1: ； Formula 1; In Equation 1, n is selected from integers from 1 to 6; R is a C1-C5 alkyl group, a C3-C6 cycloalkyl group, or a substituted phenyl group. R' is selected from hydrogen and C1-C5 alkyl groups; R1 is a halogen, alkoxy, phenoxy, cyano, or C1-C3 ester group; R2 is hydrogen or a C1-C3 alkoxy group; R3 is hydrogen.

3. The method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to claim 2, characterized in that: In Equation 1, n is selected from integers from 1 to 3; R is a C1-C3 alkyl group, a C3-C4 cycloalkyl group, an oxygen-substituted phenyl group, or a halogen-substituted phenyl group. R' is selected from hydrogen and C1-C3 alkyl groups.

4. The method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to claim 3, characterized in that: The compounds containing benzyl groups are selected from the following compounds: ； 。 5. The method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to claim 1, characterized in that: The compound containing a benzyl group is selected from the compounds shown in Formula 1: ； Formula 1; In Equation 1, n is selected from integers from 1 to 6; R is a C1-C5 alkyl, halogen, ketone, hydroxyl, amide, or C1-C3 alkoxy group; R1 is a C1-C3 alkoxy group; R2 is hydrogen or a C1-C3 alkoxy group; R3 is hydrogen. Alternatively, the compound containing a benzyl group is selected from the compounds shown in Formula 1: ； Formula 1; In Equation 1, n is selected from integers from 1 to 6; R is ; wherein R' is selected from hydrogen, unsubstituted C1-C5 alkyl, substituted or unsubstituted six-membered alicyclic group, substituted or unsubstituted heterocyclic group; R1 is a C1-C3 alkoxy group; R2 is hydrogen; R3 is hydrogen; 6. The method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to claim 5, characterized in that: In Equation 1, the two n's are selected from integers from 1 to 4.

7. The method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to claim 6, characterized in that: The compounds containing benzyl groups are selected from the following compounds: ； Alternatively, the compound containing a benzyl group is selected from the following compounds: 。 8. The method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to claim 1, characterized in that: The compound containing a benzyl group is selected from the compounds shown in Formula 1: ； Formula 1; In Equation 1, n is selected from integers from 1 to 6; R is Wherein, R" is selected from substituents containing amide groups, substituents containing NBoc groups, alkyl groups, substituted or unsubstituted phenyl groups; R1 is a C1-C3 alkoxy group; R2 is hydrogen; R3 is hydrogen.

9. The method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to claim 8, characterized in that: n is an integer selected from 1 to 4.

10. The method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to claim 9, characterized in that: The compounds containing benzyl groups are selected from the following compounds: 。 11. The method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to claim 1, characterized in that: The compound containing a benzyl group is selected from the compounds shown in Formula 1: ； Formula 1; In Equation 1, n is selected from integers from 1 to 6; R is a C1-C5 alkyl group. ; wherein R' is selected from hydrogen and unsubstituted C1-C3 alkyl groups; R1 is a substituted or unsubstituted phenyl group; R2 is hydrogen; R3 is hydrogen. or, The compound containing a benzyl group is selected from the compounds shown in Formula 1: ； Formula 1; In Equation 1, n is selected from integers from 1 to 6; R is a C1-C5 alkyl group, or a C1-C3 alkoxy-substituted phenyl group. ; where R' is selected from hydrogen; R1 is an alkyl group; R2 is hydrogen; R3 is hydrogen.

12. The method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to claim 11, characterized in that: n is an integer selected from 1 to 5; when R1 is a substituted or unsubstituted phenyl, R1 is phenyl, ester-substituted phenyl, halogen-substituted phenyl, or cyano-substituted phenyl.

13. The method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to claim 12, characterized in that: The compound containing a benzyl group is selected from the compounds shown in Formula 1: ； or, The compound containing a benzyl group is selected from the compounds shown in Formula 1: 。 14. The method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to claim 1, characterized in that: The compound containing a benzyl group is selected from the compounds shown in Formula 1: ； Formula 1; In Equation 1, n is 1; R is a substituted or substituted aryl group; R1 is hydrogen; R2 is hydrogen; R3 is hydrogen.

15. The method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to claim 14, characterized in that: When R is a substituted or substituted aryl group; R is phenyl, thiophene, biphenyl, halogen-substituted phenyl, C1-C3 alkyl-substituted phenyl, alkoxy-substituted phenyl, oxytrifluoromethyl-substituted phenyl, or C1-C3 ester-substituted phenyl.

16. The method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to claim 15, characterized in that: The compounds containing benzyl groups are selected from the following compounds: 。 17. The method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to claim 1, characterized in that: The compound containing a benzyl group is selected from the compounds shown in Formula 2, specifically: 。 18. The method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to claim 1, characterized in that: The protective atmosphere is selected from Ar gas; The hexafluorophosphate is selected from potassium hexafluorophosphate; The tetraalkyl halide is selected from at least one of tetrabutylammonium tetrafluoroborate, tetrabutylammonium chloride, and tetrabutylammonium hexafluorophosphate; and / or The organic solvent is selected from at least one of N,N-dimethylformamide, N,N-dimethyl sulfoxide, and acetonitrile; and / or, The alcohol is selected from at least one of methanol, ethanol, and isopropanol; and / or, The alcohol ether is selected from at least one of ethylene glycol methyl ethers; and / or, The molar ratio of the electrolyte to the benzyl-containing compound is 1:50%~100%; and / or, The concentration of the benzyl-containing compound in the organic solvent is 0.05~0.2 mol / L; and / or, The molar ratio of the metal catalyst to the benzyl-containing compound is 5%~50% :

1.

19. The method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to claim 18, characterized in that: The molar ratio of the metal catalyst to the benzyl-containing compound is 5%~20% : 1; When a system of water and organic solvent is used for the reaction, the volume ratio of water to organic solvent is 1:5~50; When the reaction is carried out using a system of alcohol and organic solvent, the volume ratio of alcohol to organic solvent is 1:1 to 20. When the reaction is carried out using a system of alcohol ethers and organic solvents, the volume ratio of alcohol ethers to organic solvents is 1:1 to 20.

20. The method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to claim 1, characterized in that: A constant current is applied during the electro-oxidative carbonylation reaction.

21. The method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to claim 20, characterized in that: The constant current is 1-30 mA; and / or, The energizing reaction time is 8-40 h; and / or, The reaction temperature is 10-70 ℃.

22. The method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to claim 21, characterized in that: The constant current is 5-20 mA; and / or, The energizing reaction time is 10-36 h; and / or, The energized reaction temperature is 10-60 ℃; and / or, The anode material is selected from carbon felt, platinum sheet; and / or, The post-processing includes rotary evaporation and column chromatography.

23. The method for preparing aromatic carbonyl compounds by electrochemical oxidation reaction according to claim 22, characterized in that: When the reaction is carried out using a system of water and organic solvents, the reaction temperature is 10-60 ℃. When the reaction is carried out using a system of alcohols and organic solvents, the reaction temperature is 20-60 °C. When the reaction is carried out using a system of alcohols, ethers, and organic solvents, the reaction temperature is 20-60 °C.

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