Method for the synthesis of ketone compounds based on the in situ generation of an organic calcium reagent by mechanochemistry

Abstract

This invention discloses a method for synthesizing ketone compounds based on the in-situ mechanochemical generation of organocalcium reagents. The method includes the following steps: using carboxylates and / or carboxylic acids, organohalides, and calcium metal as raw materials, mechanical ball milling is performed in the presence of liquid-assisted grinding additives, followed by acid quenching and purification to obtain ketone compounds. This invention, under mechanical ball milling conditions, allows calcium metal to form organocalcium reactive species in situ with organohalides, which then react with carboxylates and / or carboxylates formed in situ from carboxylic acids. After acid quenching and purification, ketone compounds are obtained. This method can obtain the target ketone in high yield with representative substrates, and no tertiary alcohol overaddition byproducts are observed. It solves the problems of insufficient selectivity of highly active organometallic reagents, complex pre-prepared reagent operations, cumbersome direct conversion steps of carboxylic acids, and large solvent consumption in existing technologies.

Description

Technical Field

[0001] This invention relates to the field of ketone synthesis technology, and in particular to a method for synthesizing ketone compounds based on the in-situ generation of organic calcium reagents using mechanochemical methods. Background Technology

[0002] Ketones are widely found in pharmaceuticals, pesticides, functional materials, and fine chemicals. Commonly used ketone synthesis methods include: Friedel-Crafts acylation, reactions of carboxylic acid derivatives such as acyl chlorides, acid anhydrides, Weinreb amides, and esters with organometallic reagents, transition metal-catalyzed coupling of carboxylic acid derivatives, and reductive coupling or carbonylation reactions of carboxylic acids with organohalides. Although these methods are widely used, they still have many limitations: for example, the carboxylic acid needs to be converted into highly reactive derivatives such as acyl chlorides, acid anhydrides, activated esters, and Weinreb amides beforehand; highly toxic, corrosive, or hazardous reagents are required, such as oxaloyl chloride, thionyl chloride, strong acids, or strong Lewis acids; organometallic reagents sensitive to air and moisture need to be prepared beforehand; tertiary alcohols and other byproducts are easily generated when using organolithium or Grignard reagents; or large amounts of organic solvents, transition metal catalysts, and reducing agents are required, affecting process safety, environmental friendliness, and scale-up applications.

[0003] Existing technologies report methods for preparing ketones by reacting carboxylates with pre-prepared organometallic reagents, including the use of organolithium, Grignard, organozinc, organocopper, and other organometallic compounds. While these methods avoid the carboxylic acid pre-activation step, they still have the following drawbacks: First, the required organometallic reagents usually need to be pre-prepared, transferred, or stored, are sensitive to air and moisture, and have poor operational safety and process stability. Second, when highly reactive organometallic reagents react with carboxylates or carboxylic acid derivatives, over-addition, side reactions, or limited substrate applicability may still occur. Third, some systems require the use of transition metal catalysts, special additives, or large amounts of organic solvents, affecting process economy and environmental friendliness. A simpler strategy is to generate organometallic reagents in situ from elemental metals and organohalides, followed by direct reaction with carboxylic acids. For example, it has been reported to use a lithium metal / naphthalene system to generate organolithium reagents in situ from organohalides, which then react with carboxylic acids to prepare ketones; it has also been reported to use strontium metal to react in situ with organoiodides to generate organostrontium species, which then react with carboxylic acids to obtain ketones. However, this type of method also has significant drawbacks: lithium systems rely on highly reactive organolithium species, making reaction selectivity difficult to control and prone to overaddition or side reactions; strontium systems suffer from poor cost, availability, ease of operation, and process applicability of metallic strontium, and the related reaction yields and substrate applicability remain limited. Therefore, existing technologies do not provide a universal scheme for the direct and highly selective preparation of ketone compounds from organohalides with carboxylates and / or carboxylic acids under mild and low-solvent conditions using inexpensive, low-toxicity, and widely available metal sources.

[0004] Therefore, there is an urgent need to provide a high-yield, highly selective, and scalable method for ketone synthesis to address the problems of existing methods for preparing ketone compounds from carboxylic acids, carboxylate salts, or carboxylic acid derivatives, such as long steps, the need for pre-activation of carboxylic acids, dependence on sensitive organometallic reagents, susceptibility to overaddition, numerous side reactions, large solvent consumption, or inconvenience in scale-up operations. Summary of the Invention

[0005] The purpose of this invention is to overcome the above-mentioned technical deficiencies and propose a method for synthesizing ketone compounds based on the in-situ generation of organocalcium reagents using mechanochemical methods. This method solves the technical problems of existing methods for preparing ketone compounds from carboxylic acids, carboxylate salts, or carboxylic acid derivatives, which involve long steps, the need for pre-activation of carboxylic acids, dependence on sensitive organometallic reagents, susceptibility to overaddition, numerous side reactions, large solvent consumption, or inconvenience in scale-up operations.

[0006] This invention provides a method for synthesizing ketone compounds based on in-situ mechanochemical generation of organic calcium reagents, comprising the following steps: Ketone compounds were obtained by mechanical ball milling of carboxylate salts and / or carboxylic acids, organohalides, and calcium metals in the presence of liquid-assisted grinding additives, followed by acid quenching and separation purification.

[0007] Compared with the prior art, the beneficial effects of the present invention include: This invention involves in-situ formation of an organocalcanthate reactive species from calcium metal and organohalides under mechanical ball milling conditions. This reacts with carboxylates and / or carboxylates formed in situ from carboxylic acids. Following acid quenching and purification, ketone compounds are obtained. This method yields the target ketone in high yields from representative substrates without observing over-addition byproducts of tertiary alcohols. It overcomes the problems of insufficient selectivity of highly reactive organometallic reagents, complex pre-preparation of reagents, cumbersome direct conversion steps of carboxylic acids, and large solvent consumption in existing technologies. Attached Figure Description

[0008] Figure 1 This is the 1H NMR spectrum of 4-methylbenzophenone prepared in Example 1 of this invention; Figure 2 This is the 1H NMR spectrum of 4-fluorobenzophenone prepared in Example 18 of this invention; Figure 3 This is the 1H NMR spectrum of 4-methoxybenzophenone prepared in Example 24 of this invention; Figure 4 This is the 1H NMR spectrum of 2-benzoylbenzofuran prepared in Example 35 of this invention; Figure 5 This is the 1H NMR spectrum of cyclohexylphenyl ketone prepared in Example 40 of this invention; Figure 6 This is the 1H NMR spectrum of 4-iodobenzophenone prepared in Example 45 of this invention; Figure 7 This is the 1H NMR spectrum of 4-fluoro-4-methylbenzophenone prepared in Example 55 of this invention; Figure 8 This is the 1H NMR spectrum of cyclohexyl(4-methylphenyl) ketone prepared in Example 68 of this invention; Figure 9 This is the 1H NMR spectrum of 4,4′-difluorobenzophenone prepared in Example 69 of this invention; Figure 10 The (5-bromo-2-chlorophenyl)(4-ethoxyphenyl) methyl ketone prepared in Example 70 of this invention The proton NMR spectrum; Figure 11 This is the 1H NMR spectrum of 1,5-diphenyl-1-pentanone prepared in Example 71 of this invention; Figure 12 This is the 1H NMR spectrum of [4-(2-chloroethoxy)phenyl]phenyl methyl ketone prepared in Example 72 of this invention. Detailed Implementation

[0009] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0010] Existing methods for preparing ketones by reacting carboxylates with pre-prepared organometallic reagents, including those using organolithium, Grignard, organozinc, organocopper, and other organometallic compounds, have the following drawbacks: First, the required organometallic reagents usually need to be pre-prepared, transferred, or stored, are sensitive to air and moisture, and have poor operational safety and process stability. Second, when highly reactive organometallic reagents react with carboxylates or carboxylic acid derivatives, overaddition, side reactions, or limited substrate applicability may still occur. Third, some systems require the use of transition metal catalysts, special additives, or large amounts of organic solvents, affecting process economy and environmental friendliness. Existing methods for preparing ketones by in-situ generation of organometallic reagents from elemental metals (lithium, strontium) and organohalides, followed by direct reaction with carboxylic acids, have significant drawbacks: lithium systems rely on highly reactive organolithium species, making reaction selectivity difficult to control and prone to overaddition or side reactions; strontium systems suffer from poor price, availability, ease of operation, and process applicability of metallic strontium, and the related reaction yields and substrate applicability remain limited.

[0011] Calcium metal has advantages such as low cost, low toxicity, and abundant sources. However, calcium metal surfaces are prone to oxidation or passivation layers, making it difficult to continuously expose fresh metal surfaces under conventional liquid phase conditions. At the same time, the process of calcium metal forming organocallidus species with organohalides is not as mature and controllable as that of lithium, magnesium, and other metals. Even if organocallidus species are formed, it is not clear whether they can preferentially undergo acylation reactions in the presence of carboxylates, rather than halogen reduction, coupling, carboxylate deactivation, metal surface passivation, or other side reactions.

[0012] Based on this, the present invention is proposed.

[0013] This invention provides a method for synthesizing ketone compounds based on in-situ mechanochemical generation of organic calcium reagents, comprising the following steps: Ketone compounds were obtained by mechanical ball milling of carboxylate salts and / or carboxylic acids, organohalides, and calcium metals in the presence of liquid-assisted grinding additives, followed by acid quenching and separation purification.

[0014] The specific mechanism of action in this invention is as follows: Under the impact and shearing action of ball milling, the oxide / passivation layer on the calcium metal surface is continuously broken and renewed. The fresh calcium surface undergoes insertion or electron transfer processes with organohalides to form organic calcium species. Liquid-assisted grinding additives coordinate with the calcium center, improving the thermodynamic stability of the organic calcium species and enhancing solid mixing and reaction contact. This organic calcium species undergoes nucleophilic addition to carboxylates to form calcium-coordinated geminal diol-type tetrahedral intermediates. These intermediates are stabilized by the strong coordination between the geminal diol hydroxyl anion and the calcium ion, reducing the possibility of further attack by a second equivalent organometallic reagent. The intermediates are then converted into corresponding ketone compounds through acid quenching. The above mechanism explains why this system can directly yield ketones from carboxylates and / or carboxylic acids with minimal over-addition tertiary alcohol byproducts.

[0015] In this invention, the reaction formula is as follows: ; Among them, R 1 It can be aryl (including but not limited to at least one of phenyl, naphthyl, anthracene, phenanthryl, pyrene, etc.), heteroaryl (including but not limited to thiophene, benzothiophene, benzofuran, dibenzofuran, dibenzothiophene, pyridine, pyrazole, etc.), C 1-12 Alkyl (including C) 1-12 Linear alkyl, C 1-12 At least one of cycloalkyl groups, alkynyl substituents, etc., wherein the aryl, heteroaryl, C 1-12 The alkyl or alkynyl substituent may be further optionally coated with one or more halogens, C 1-12 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-12 Alkyl, halogen-substituted C 1-6 Alkoxy, thioether, C 1-3 Alkylthio, C 1-3 Alkyl-substituted amino, phenyl, etc. substitutions; R 2 It can be aryl (including but not limited to at least one of phenyl, naphthyl, anthracene, phenanthryl, pyrene, etc.), heteroaryl (including but not limited to thiophene, benzothiophene, benzofuran, dibenzofuran, dibenzothiophene, pyridine, pyrazole, etc.), C 1-12 Alkyl (including C) 1-12 Linear alkyl, C 1-12 At least one of cycloalkyl groups, etc., wherein the aryl, heteroaryl or C 1-12 The alkyl group may be further optionally coated with one or more halogens, C 1-12 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-12 Alkyl, halogen-substituted C 1-6 Alkoxy, thioether, C 1-3 Alkylthio, C1-3 Alkyl-substituted amino, phenyl, etc. substitutions; X can be at least one of iodine or bromine, preferably iodine; when polyhalogenated substrates are present, the reaction is preferably carried out at the CI bond to preserve the C-Br bond; for diiodine substrates, monofunctionalized products can be obtained. M can be at least one of Na, K, Li, etc., preferably Na.

[0016] In this invention, the carboxylate and / or carboxylic acid are aromatic carboxylic acids, C 1-12 At least one of alkyl carboxylic acids or their corresponding carboxylates.

[0017] Among them, the aromatic carboxylic acid is an unsubstituted aromatic carboxylic acid, a monosubstituted aromatic carboxylic acid, or a polysubstituted aromatic carboxylic acid; when the aromatic carboxylic acid is a monosubstituted or polysubstituted aromatic carboxylic acid, the substituents on its aromatic ring are each independently selected from halogens, C, and D. 1-12 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-12 Alkyl, halogen-substituted C 1-6 Alkoxy, C 1-3 Alkylthio, C 1-3 Alkyl-substituted amino or phenyl groups; aryl groups are selected from at least one of phenyl, naphthyl, anthraceneyl, phenanthryl, and pyrene.

[0018] Among them, C 1-12 Alkyl carboxylic acids are unsubstituted C 1-12 Alkyl carboxylic acids, monosubstituted C 1-12 Alkyl carboxylic acids or polysubstituted C 1-12 Alkyl carboxylic acids; when C 1-12 Alkyl carboxylic acids are mono- or poly-substituted C. 1-12 In the case of alkylcarboxylic acids, the substituents on the carbon chain or carbon ring are each independently selected from halogens, C... 1-12 Alkyl, C 1-6 Alkoxy, C 1-3 Alkyl-substituted amino or phenyl groups; the alkyl group is selected from at least one of linear alkyl or cycloalkyl groups.

[0019] The carboxylate is at least one of sodium, potassium, and lithium salts, preferably sodium salt.

[0020] This invention does not limit the source of the carboxylate, and those skilled in the art can choose according to the actual situation. For example, it can be purchased directly or prepared by oneself.

[0021] In some specific embodiments of the present invention, the carboxylate is a sodium salt, and the preparation steps of the carboxylate are as follows: NaH and carboxylic acid are dispersed in anhydrous THF, and a stirring reaction is carried out at room temperature under a protective atmosphere (including but not limited to nitrogen or argon atmosphere, etc.), followed by extraction and concentration to obtain sodium carboxylate.

[0022] In some specific embodiments of the present invention, the carboxylate and / or carboxylic acid are selected from at least one of the following compounds or the corresponding carboxylates of the following compounds: .

[0023] In this invention, the organohalides are aryl iodides, aryl bromides, heteroaryl iodides, and C. 1-12 At least one of alkyl iodides.

[0024] Among them, the aryl iodide is an unsubstituted aryl iodide, a monosubstituted aryl iodide, or a polysubstituted aryl iodide; when the aryl iodide is a monosubstituted or polysubstituted aryl iodide, the substituents on its aromatic ring are each independently selected from halogens, C 1-12 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-12 Alkyl, halogen-substituted C 1-6 Alkoxy, C 1-3 Alkylthio, C 1-3 Alkyl-substituted amino or phenyl groups; aryl groups are selected from at least one of phenyl, naphthyl, anthraceneyl, phenanthryl, and pyrene.

[0025] Among them, the aryl bromide is an unsubstituted aryl bromide, a monosubstituted aryl bromide, or a polysubstituted aryl bromide; when the aryl bromide is a monosubstituted or polysubstituted aryl bromide, the substituents on its aromatic ring are each independently selected from halogens, C... 1-12 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-12 Alkyl, halogen-substituted C 1-6 Alkoxy, C 1-3 Alkylthio, C 1-3 Alkyl-substituted amino or phenyl groups; aryl groups are selected from at least one of phenyl, naphthyl, anthraceneyl, phenanthryl, and pyrene.

[0026] Among them, the heteroaryl iodide is an unsubstituted heteroaryl iodide, a monosubstituted heteroaryl iodide, or a polysubstituted heteroaryl iodide; when the heteroaryl iodide is a monosubstituted or polysubstituted heteroaryl iodide, the substituents on its heteroaryl ring are each independently selected from halogens, C 1-12 Alkyl, C 1-6 Alkoxy, C 1-3 Alkyl-substituted amino group; heteroaryl group is selected from at least one of thienyl, benzothienyl, benzofuranyl, dibenzofuranyl, dibenzothienyl, pyridyl, and pyrazolyl.

[0027] Among them, C 1-12 Alkyl iodides are unsubstituted C 1-12 Alkyl iodides, monosubstituted C 1-12 Alkyl iodides or polysubstituted C 1-12Alkyl iodides; when C 1-12 Alkyl iodides are monosubstituted or polysubstituted C 1-12 In the case of alkyl iodides, the substituents on the carbon chain or carbon ring are each independently selected from halogens, C... 1-12 Alkyl, C 1-6 Alkoxy, C 1-3 Alkyl-substituted amino or phenyl groups; the alkyl group is selected from at least one of linear alkyl or cycloalkyl groups.

[0028] In some specific embodiments of the present invention, the organohalides are selected from at least one of the following compounds: .

[0029] In this invention, the calcium metal can be calcium particles, calcium chips, calcium powder, calcium blocks obtained by shearing, or other calcium sources whose surfaces can be renewed by mechanical force. This invention does not limit the types of calcium metal used, but commercial calcium particles are preferred.

[0030] In this invention, the liquid-assisted grinding additive is an ether-based additive, including but not limited to at least one selected from 2-methyltetrahydrofuran (2-MeTHF), tetrahydrofuran (THF), diethyl ether, 2,5-dimethyltetrahydrofuran, methyl tert-butyl ether, and 1,2-dimethoxyethane, preferably 2-methyltetrahydrofuran or tetrahydrofuran. By using the above-mentioned liquid-assisted grinding additive, especially 2-methyltetrahydrofuran or tetrahydrofuran, this invention can significantly reduce solvent usage while improving the formation and stability of organocalcium species.

[0031] In this invention, carboxylates are used as raw materials, and the molar ratio of carboxylates to calcium metal is 1:(1.0-5.0), preferably 1:(1.2-3.0), and more preferably 1:1.5.

[0032] In this invention, carboxylates are used as raw materials, and the molar ratio of carboxylates to organic halides is 1:(1.0-5.0), preferably 1:(1.5-3.0), and more preferably 1:2.0.

[0033] In this invention, carboxylates are used as raw materials, and the molar ratio of carboxylates to liquid auxiliary grinding additives is 1:(0.5-20), preferably 1:(1.0-8.0), and more preferably 1:4.0.

[0034] In this invention, carboxylic acid is used as the raw material, and the molar ratio of carboxylic acid to calcium metal is 1:(1.5-8.0), preferably 1:(2.0-5.0), and more preferably 1:3.0.

[0035] In this invention, carboxylic acid is used as the raw material, and the molar ratio of carboxylic acid to organic halide is 1:(1.5-8.0), preferably 1:(2.0-5.0), and more preferably 1:3.0.

[0036] In this invention, carboxylic acid is used as raw material, and the molar ratio of carboxylic acid to liquid auxiliary grinding additive is 1:(0.5-20), preferably 1:(1.0-8.0), and more preferably 1:4.0.

[0037] In this invention, carboxylates and / or carboxylic acids, organic halides, and calcium metals are used as raw materials, and mechanical ball milling is performed in the presence of liquid-assisted grinding additives, including: Carboxylates and / or carboxylic acids, organohalides, calcium metals, liquid grinding aids, and grinding balls are added to a ball mill jar, which is then sealed, and the mixture is oscillated and ground in a ball mill.

[0038] Preferably, carboxylates and / or carboxylic acids, organohalides, calcium metals, liquid-assisted grinding additives, and grinding balls are added to the grinding jar in a protective atmosphere (including but not limited to nitrogen or argon atmospheres) or air.

[0039] Preferably, a stainless steel grinding jar and stainless steel balls are used.

[0040] In this invention, during the mechanical ball milling process, the ball milling frequency is 10-50 Hz, preferably 20-40 Hz, and more preferably 30 Hz; the reaction time is 5-300 min, preferably 30-120 min, and more preferably 60 min; and the reaction temperature is 0-60 ℃.

[0041] In this invention, the acid quenching process includes: quenching the reaction mixture with an acidic aqueous solution (including but not limited to dilute hydrochloric acid) to convert organic calcium or calcium coordination intermediates into the target ketone product.

[0042] Preferably, the concentration of the acidic aqueous solution is 0.1-6 mol / L, more preferably 0.5-3 mol / L, and even more preferably 1 mol / L.

[0043] Preferably, the ratio of carboxylate and / or carboxylic acid to acidic aqueous solution is 1 mmol : 1-20 mL, more preferably 1 mmol : 2-10 mL, and even more preferably 1 mmol : 3-5 mL.

[0044] In this invention, the separation and purification methods include, but are not limited to, extraction with organic solvents (including but not limited to dichloromethane), short silica gel column, column chromatography, preparative thin-layer chromatography, crystallization or recrystallization, etc.

[0045] Example 1 In a nitrogen-filled glove box, sodium benzoate (0.2 mmol, 1.0 equiv), 4-iodotoluene (0.4 mmol, 2.0 equiv), calcium granules (0.3 mmol, 1.5 equiv), and 2-MeTHF (0.8 mmol, 4.0 equiv) were added to a 1.5 mL stainless steel ball mill jar, along with two 6.0 mm diameter stainless steel balls. The jar was sealed and placed in a Retsch MM400 ball mill, where it was milled at 30 Hz for 60 minutes. After the reaction was complete, the mixture was quenched with 1 mL of 1M dilute hydrochloric acid. The resulting mixture was purified by silica gel short column chromatography and preparative thin-layer chromatography to obtain 4-methylbenzophenone with an NMR yield of 95%.

[0046] Its chemical structural formula is:

[0047] Separation yield: 91%, white solid.

[0048] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.80 – 7.72 (m, 4H), 7.59-7.57 (m,1H), 7.47-7.45 (m, 2H), 7.28 (m, 2H), 2.44 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ196.6, 143.4, 138.0, 135.0, 132.3, 130.4, 130.0, 129.1, 128.3, 21.8. HRMS(ESI): [M+H] + Calculated value: C14H12O: 197.0960; Measured value: 197.0954. MIR (cm -1 ): 2972,2870, 1648, 1601, 1584, 755. Example 2 The preparation steps were the same as in Example 1, except that the reaction was carried out after feeding the material into the air to obtain 4-methylbenzophenone with an NMR yield of 92%.

[0049] Example 3 The preparation steps were the same as in Example 1, except that 2-MeTHF (0.8 mmol, 4.0 equiv) was replaced with an equal amount of THF to obtain 4-methylbenzophenone with an NMR yield of 90%.

[0050] Example 4 The preparation steps were the same as in Example 1, except that 2-MeTHF (0.8 mmol, 4.0 equiv) was replaced with an equimolar amount of DME to obtain 4-methylbenzophenone with an NMR yield of 68%.

[0051] Example 5 The preparation steps were the same as in Example 1, except that 2-MeTHF (0.8 mmol, 4.0 equiv) was replaced with an equal amount of diethyl ether to obtain 4-methylbenzophenone with an NMR yield of 56%.

[0052] Example 6 The preparation steps were the same as in Example 1, except that 2-MeTHF (0.8 mmol, 4.0 equiv) was replaced with an equal amount of 2,5-dimethyltetrahydrofuran to obtain 4-methylbenzophenone with an NMR yield of 51%.

[0053] Example 7 The preparation steps were the same as in Example 1, except that 2-MeTHF (0.8 mmol, 4.0 equiv) was replaced with an equal amount of MTBE to obtain 4-methylbenzophenone with an NMR yield of 26%.

[0054] Example 8 The preparation steps were the same as in Example 1, except that the amount of 4-iodotoluene (0.4 mmol, 2.0 equiv) was reduced to 1.2 equiv to obtain 4-methylbenzophenone with an NMR yield of 68%.

[0055] Example 9 The preparation steps were the same as in Example 1, except that the amount of 4-iodotoluene (0.4 mmol, 2.0 equiv) was reduced to 1.5 equiv to obtain 4-methylbenzophenone with an NMR yield of 87%.

[0056] Example 10 The preparation steps were the same as in Example 1, except that the reaction time was reduced from 60 minutes to 30 minutes to obtain 4-methylbenzophenone with an NMR yield of 81%.

[0057] Example 11 The preparation steps were the same as in Example 1, except that sodium benzoate (0.2 mmol, 1.0 equiv) was replaced with potassium benzoate (0.2 mmol, 1.0 equiv) to obtain 4-methylbenzophenone with an NMR yield of 63%.

[0058] Example 12 The preparation steps were the same as in Example 1, except that sodium benzoate (0.2 mmol, 1.0 equiv) was replaced with lithium benzoate (0.2 mmol, 1.0 equiv) to obtain 4-methylbenzophenone with an NMR yield of 21%.

[0059] Example 13 The preparation steps were the same as in Example 1, except that 4-iodotoluene was replaced with an equal amount of 4-bromotoluene to obtain 4-methylbenzophenone with an NMR yield of 43%.

[0060] Example 14 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 3-iodotoluene, resulting in: 3-Methylbenzophenone

[0061] Separation yield: 85%, white solid.

[0062] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.81-7.79 (d, J = 8 Hz, 2H), 7.63-7.57 (m, 3H), 7.50-7.47 (t, J = 6 Hz, 2H), 7.42-7.37 (m, 2H), 2.43 (s, 3H); 13 C NMR (101 MHz, CDCl3) δ 197.1, 138.3, 137.8, 137.7, 133.3, 132.5, 130.6,130.2, 128.4, 128.2, 127.5, 21.5. HRMS (ESI): [M+H] + Calculated value: C14H12O: 197.0960; Measured value: 197.0941. MIR (cm -1 ): 2970, 2870, 1648, 1600, 1580, 1450, 1375, 750.

[0063] Example 15 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 2-iodotoluene, resulting in: 2-Methylbenzophenone

[0064] Separation yield: 78%, white solid.

[0065] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 7.0 Hz, 2H), 7.56 (t,J = 7.4 Hz, 1H), 7.46 (t, J = 7.9 Hz, 2H), 7.43 – 7.34 (m, 1H), 7.29 (t, J =1.5 Hz, 1H), 7.26 – 7.22 (m, 2H), 2.33 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ198.8, 138.7, 137.8, 136.9, 133.3, 131.1, 130.4, 130.3, 128.6, 128.6, 125.3,20.1. HRMS (ESI): [M+H] + Calculated value: C14H12O: 197.0960; Measured value: 197.0942. MIR (cm) -1 ):3060, 2870, 1645, 1600, 1450, 750.

[0066] Example 16 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of iodobenzene, resulting in: Benzene

[0067] Separation yield: 82%, white solid.

[0068] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 5.5 Hz, 4H), 7.63 –7.56 (m, 2H), 7.48 (d, J = 7.3 Hz, 4H). 13 C NMR (101 MHz, CDCl3) δ 196.9,137.7, 132.5, 130.2, 128.4. HRMS (ESI): [M+H] + Calculated value: C13H10O: 183.0804; Measured value: 183.0799.

[0069] Example 17 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 4-tert-butyliodobenzene, resulting in: 4-tert-butylbenzophenone

[0070] Separation yield: 88%, colorless oily substance.

[0071] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.85 – 7.73 (m, 3H), 7.58 (t, J =7.4 Hz, 1H), 7.54 – 7.42 (m, 3H), 1.37 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ196.6, 156.3, 138.0, 134.9, 132.3, 130.2, 130.1, 128.3, 125.4, 35.2, 31.2.HRMS (ESI): [M+H] + Calculated value: C17H18O: 239.1430; Measured value: 239.1428.

[0072] Example 18 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 4-fluoroiodobenzene, resulting in: 4-Fluorobenzophenone

[0073] Separation yield: 86%, white solid.

[0074] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.85 (m, 2H), 7.77 (m, 2H), 7.60 (t, J = 8.1 Hz, 1H), 7.50 (m, 2H), 7.23 – 7.13 (m, 2H). 13 C NMR (101 MHz, CDCl3) δ 195.4, 166.8, 137.6, 133.9, 132.7, 132.6, 130.0, 128.5, 115.7 (d, J= 21.9 Hz). 19 F NMR (376 MHz, CDCl3) δ-105.83. HRMS (ESI): [M+H] + Calculated value: C13H9OF: 201.0710; Measured value: 201.0705.

[0075] Example 19 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 3-fluoroiodobenzene, resulting in: 3-Fluorobenzophenone

[0076] Separation yield: 70%, white solid.

[0077] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 7.1 Hz, 2H), 7.63 –7.55 (m, 2H), 7.52 – 7.42 (m, 4H), 7.29 (td, 1H). 13 C NMR (101 MHz, CDCl3) δ195.5 (d, J = 2 Hz), 161.3 (d, J = 246.5 Hz), 139.7 (d, J = 6.3 Hz), 137.1,132.9, 130.1, 129.9, 128.5, 125.9 (d, J = 3.0 Hz), 119.4 (d, J = 21.2 Hz), 116.8 (d, J = 22.3 Hz). 19 F NMR (376 MHz, CDCl3) δ -111.86. HRMS (ESI): [M+H] + Calculated value: C13H9OF: 201.0710; Measured value: 201.0712.

[0078] Example 20 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 4-trifluoromethyliodobenzene, resulting in: 4-Trifluoromethylbenzophenone

[0079] Separation yield: 85%, colorless oily substance.

[0080] Characterization data: 1 H NMR (600 MHz, CDCl3) δ 7.90 (d, J = 7.8 Hz, 2H), 7.78 (dd,J = 29.7, 7.8 Hz, 4H), 7.63 (t, J = 7.5 Hz, 1H), 7.51 (t, J = 7.7 Hz, 2H). 13CNMR (151 MHz, CDCl3) δ 195.6, 140.8, 136.8, 133.1, 130.2, 130.1 (d, J = 4.3Hz), 128.6, 125.4 (q, J = 3.7 Hz), 122.8 (q, J = 272.6 Hz). 19 F NMR (565 MHz, CDCl3) δ-63.00. HRMS (ESI): [M+Li] + Calculated value: C14H9OF3: 257.0760; Measured value: 257.0740.

[0081] Example 21 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 4-(trifluoromethoxy)iodobenzene, yielding: Phenylacetyl-4-trifluoromethoxyphenyl ketone

[0082] Separation yield: 61%, colorless oily substance.

[0083] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 8.5 Hz, 2H), 7.79 (d,J = 8.3 Hz, 2H), 7.61 (t, J = 6.8 Hz, 1H), 7.50 (t, J = 7.7 Hz, 2H), 7.32 (d,J = 8.4 Hz, 2H). 13 C NMR (101 MHz, CDCl3) δ 195.3, 152.2 (q, J = 2.1 Hz), 137.2, 136.0, 132.9, 132.1, 130.1, 128.5, 120.3 (q, J = 259.0 Hz). 19 F NMR (376MHz, CDCl3) δ -57.48. HRMS (ESI): [M+H] + Calculated value: C14H9O2F3: 267.0627; Measured value: 267.0624. MIR (cm) -1 ):3060, 2950, ​​1645, 1580, 1450, 1150, 850.

[0084] Example 22 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 3-(trifluoromethoxy)iodobenzene, yielding: Phenyl-3-trifluoromethoxyphenyl ketone

[0085] Separation yield: 58%, colorless oily substance.

[0086] Characterization data: 1 H NMR (600 MHz, CDCl3) δ 7.80 (d, J = 6.8 Hz, 2H), 7.73 (d,J = 7.7 Hz, 1H), 7.66 (s, 1H), 7.62 (t, J = 7.4 Hz, 1H), 7.56 – 7.47 (m, 3H),7.45 (d, J = 8.3 Hz, 1H). 13 C NMR (151 MHz, CDCl3) δ 195.0, 149.2 (q, J = 2.1Hz), 139.5, 136.9, 133.0, 130.0, 129.9, 128.5, 128.4, 124.8, 122.4, 121.3,120.0 (q, J = 260.0 Hz). 19 F NMR (565 MHz, CDCl3) δ -57.87. HRMS (ESI): [M+H] + Calculated value: C14H9O2F3: 267.0627; Measured value: 267.0615. MIR (cm) -1 ):3026, 1652, 1275, 1120,1087, 760.

[0087] Example 23 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 4-chloroiodobenzene, resulting in: 4-Chlorobenzophenone

[0088] Separation yield: 97%, colorless oily substance.

[0089] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.83 – 7.72 (m, 4H), 7.60 (t, J =7.4 Hz, 1H), 7.55 – 7.43 (m, 4H).13 C NMR (101 MHz, CDCl3) δ 195.6, 139.0,137.3, 136.0, 132.8, 131.6, 130.0, 128.8, 128.5. HRMS (ESI): [M+H] + Calculated value: C13H9OCl: 217.0415; Measured value: 217.0414.

[0090] Example 24 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 4-methoxyiodobenzene, resulting in: 4-Methoxybenzophenone

[0091] Separation yield: 89%, colorless oily substance.

[0092] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.83 (m 2H), 7.75 (m, 2H), 7.56 (t,J = 7.4 Hz, 1H), 7.47 (m, 2H), 6.96 (m, 2H), 3.88 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 195.7, 163.3, 138.4, 132.7, 132.0, 129.9 (d, J = 6.7 Hz), 128.3,113.7, 55.6. HRMS (ESI): [M+H] + Calculated value: C14H12O2: 213.0910; Measured value: 203.0900.

[0093] Example 25 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 3,5-dimethoxyiodobenzene, resulting in: 3,5-Dimethoxyphenylbenzophenone

[0094] Separation yield: 89%, colorless oily substance.

[0095] Characterization data: 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 8.6 Hz, 2H), 7.59 (t,J = 6.7 Hz, 1H), 7.48 (t, J = 7.8 Hz, 2H), 6.93 (s, 2H), 6.68 (d, J = 2.7 Hz,1H), 3.83 (s, 6H). 13 C15H14O3 NMR (101 MHz, CDCl3) δ 196.5, 160.6, 139.6, 137.6, 132.6, 130.1, 128.4, 108.0, 104.9, 55.5. HRMS (ESI): [M+K]+ Calculated value: C15H14O3: 281.0574; Measured value: 281.0570.

[0096] Example 26 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 4-methylthioiodobenzene, resulting in: 4-Methylthiobenzophenone

[0097] Separation yield: 95%, white solid.

[0098] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.81 – 7.72 (m, 4H), 7.61 – 7.55(m, 1H), 7.48 (t, J = 7.5 Hz, 2H), 7.29 (d, J = 8.5 Hz, 2H), 2.54 (s, 3H). 13 CNMR (101 MHz, CDCl3) δ 196.2, 145.6, 138.2, 133.9,132.5,131.0,130.1,128.6,125.1,15.1. HRMS (ESI): [M+H] + Calculated value: C14H12OS: 229.0681; Measured value: 229.0670. MIR (cm) -1 ):3058, 2920, 1650, 1188, 660.

[0099] Example 27 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 4-dimethylaminoiodobenzene, resulting in: 4-Dimethylaminobenzophenone

[0100] Separation yield: 78%, colorless oily substance.

[0101] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 9.0 Hz, 2H), 7.72 (d,J = 6.9 Hz, 2H), 7.56 – 7.50 (m, 1H), 7.45 (t, J = 7.3 Hz, 2H), 6.69 (d, J =9.1 Hz, 2H), 3.07 (s, 6H). 13 C NMR (101 MHz, CDCl3) δ 195.3, 153.3, 139.4,132.9, 131.2, 129.6, 128.1, 124.9, 110.7, 40.2. HRMS (ESI): [M+H] + Calculated value: C15H15ON: 226.1226; Measured value: 226.1217.

[0102] Example 28 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 4-iodobiphenyl, resulting in: 4-Phenylacetone

[0103] Separation yield: 78%, colorless oily substance.

[0104] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.89 (d, J = 8.0 Hz, 2H), 7.84 (d,J = 7.6 Hz, 2H), 7.70 (d, J =8.0 Hz, 2H), 7.65 (d, J = 7.6 Hz, 2H), 7.60 (t,J = 7.4 Hz, 1H), 7.52-7.46 (m, 4H), 7.40(t, J = 7.2 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 196.5, 145.3, 140.0, 137.9, 136.3, 132.5, 130.9, 130.1, 129.1,128.4, 128.3, 127.4, 127.1. HRMS (ESI): [M+H] + Calculated value: C19H14O: 259.1117; Measured value: 259.1104.

[0105] Example 29 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 2-iodobiphenyl, resulting in: 2-Benzoylbiphenyl

[0106] Separation yield: 70%, colorless oily substance.

[0107] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.66 (dd, J = 8.3, 1.4 Hz, 2H), 7.62 – 7.57 (m, 1H), 7.55 – 7.47 (m, 3H), 7.44 – 7.39 (m, 1H), 7.31 – 7.25(m, 4H), 7.24 – 7.13 (m, 3H). 13 C NMR (101 MHz, CDCl3) δ 198.9, 141.2, 140.3,139.0, 137.5, 132.9, 130.5, 130.2, 130.0, 129.1, 128.9, 128.4, 128.2, 127.4,127.2. HRMS (ESI): [M+H] + Calculated value: C19H4O: 259.1117; Measured value: 259.1103. MIR (cm) -1 ):3060, 3025, 1650, 1590, 1315, 696.

[0108] Example 30 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 1-iodonaphthalene, resulting in: 1-Benzoylnaphthalene

[0109] Separation yield: 90%, colorless oily substance.

[0110] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 8.13 – 8.08 (m, 1H), 8.01 (d, J =8.2 Hz, 1H), 7.93 (dd, J = 8.1, 1.6 Hz, 1H), 7.88 (dd, J = 7.1, 1.4 Hz, 2H), 7.62 – 7.57 (m, 2H), 7.56 – 7.43 (m, 5H). 13 C NMR (101 MHz, CDCl3) δ 198.2,138.4, 136.4, 133.8, 133.4, 131.4, 131.1, 130.5, 128.6, 128.5, 127.9, 127.4,126.6, 125.8, 124.4. HRMS (ESI): [M+H] + Calculated value: C17H12O: 233.0961; Measured value: 233.0950.

[0111] Example 31 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 2-iodonaphthalene, resulting in: 2-Benzoylnaphthalene

[0112] Separation yield: 86%, colorless oily substance.

[0113] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 8.27 (d, J = 1.1 Hz, 1H), 7.96 (d,J = 1.3 Hz, 2H), 7.92 (d, J = 8.1 Hz, 2H), 7.87 (dd, J = 8.2, 1.4 Hz, 2H),7.67 – 7.59 (m, 2H), 7.59 – 7.49 (m, 3H). 13 HRMS (ESI): [M+H] +Calculated value: C17H12O: 233.0961; Measured value: 233.0953.

[0114] Example 32 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 9-iodophenanthrene, resulting in: 9-Phenylacetyl phenyl ketone

[0115] Separation yield: 75%, colorless oily substance.

[0116] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 8.83 – 8.71 (m, 2H), 8.12 (dd, J =8.3, 1.3 Hz, 1H), 7.96 (dd, J = 8.3, 1.4 Hz, 2H), 7.93 – 7.83 (m, 2H), 7.79 –7.57 (m, 5H), 7.48 (t, J = 7.8 Hz, 2H). 13 C NMR (101 MHz, CDCl3) δ 198.1,138.3, 135.4, 133.5, 131.4, 130.7, 130.6, 130.2, 129.6, 129.5, 129.3, 128.7,128.4, 127.3, 127.3, 127.3, 126.7, 123.1, 122.8. HRMS (ESI): [M+H] + Calculated value: C21H14O: 283.1117; Measured value: 283.1110. MIR (cm) -1 ):2850, 1816, 1645, 1023, 790,564.

[0117] Example 33 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 2-iodothiophene, resulting in: 2-Benzoylthiophene

[0118] Separation yield: 86%, brown solid.

[0119] Characterization data: 1H NMR (400 MHz, CDCl3) δ 7.90 – 7.83 (m, 2H), 7.72 (dd, J =5.0, 1.2 Hz, 1H), 7.65 (dd, J = 3.8, 1.1 Hz, 1H), 7.59 (t, J = 7.4 Hz, 1H), 7.50 (t, J = 7.6 Hz, 2H), 7.16 (dd, J = 5.0, 3.7 Hz, 1H). 13 C NMR (101 MHz, CDCl3) δ 188.4, 143.8, 138.2, 135.0, 134.3, 132.4, 129.3, 128.5, 128.1. HRMS(ESI): [M+H] + Calculated value: C11H8OS: 189.0369; Measured value: 189.0364.

[0120] Example 34 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 2-iodobenzothiophene, resulting in: Benzo[b]thiophene-2-ylphenyl ketone

[0121] Separation yield: 90%, colorless oily substance.

[0122] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.96 – 7.84 (m, 5H), 7.67 – 7.61 (m, 1H), 7.51 (m, 3H), 7.42 (m, 1H). 13 C NMR (101 MHz, CDCl3) δ 189.8, 143.2,142.8, 139.2, 138.0, 132.6, 132.4, 129.4, 128.6, 127.6, 126.2, 125.2, 123.0.HRMS (ESI): [M+H] + Calculated value: C15H10OS: 239.0525; Measured value: 239.0521. MIR (cm) -1 ):3058,1640, 1217, 971, 674.

[0123] Example 35 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 2-iodobenzofuran, resulting in: 2-Benzoylbenzofuran

[0124] Separation yield: 75%, colorless oily substance.

[0125] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 8.05 (d, J = 6.9 Hz, 2H), 7.74 (d,J = 7.9 Hz, 1H), 7.64 (t, J = 7.4 Hz, 2H), 7.59 – 7.48 (m, 4H), 7.34 (t, J =7.1 Hz, 1H). 13 C NMR (101 MHz, CDCl3) δ 184.6, 156.1, 152.3, 137.3, 133.0,129.6, 128.7, 128.5, 127.1, 124.1, 123.4, 116.7, 112.7. HRMS (ESI): [M+H] + Calculated value: C15H10O2: 223.0754; Measured value: 223.0746.

[0126] Example 36 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 4-iododibenzofuran, resulting in: 4-Dibenzofuranylphenyl ketone

[0127] Separation yield: 62%, colorless oily substance.

[0128] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 8.15 (dd, J = 7.7, 1.3 Hz, 1H), 8.00 (d, J = 6.5 Hz, 1H), 7.92 (d, J = 7.0 Hz, 2H), 7.71 (dd, J = 7.6, 1.3Hz, 1H), 7.63 (t, J = 7.4 Hz, 1H), 7.56 – 7.41 (m, 5H), 7.41 – 7.35 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 194.1, 156.5, 154.0, 137.8, 133.2, 130.3, 128.8,128.5, 127.9, 125.7, 124.3, 123.4, 123.3, 122.6, 120.8, 112.3. HRMS (ESI): [M+H] + Calculated value: C19H12O2: 273.0910; Measured value: 273.0899. MIR (cm -1 ):3056, 2925, 1660,1320, 990, 620.

[0129] Example 37 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 4-iododibenzothiophene, resulting in: Dibenzo[b,d]thiophene-4-yl(phenyl)methyl ketone

[0130] Separation yield: 62%, colorless oily substance.

[0131] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 8.40 (d, J = 8.0 Hz, 1H), 8.21 (d,J = 9.0 Hz, 1H), 7.96 (dd, J = 7.4, 1.8 Hz, 1H), 7.91 (d, J = 7.5 Hz, 1H), 7.80 (d, J = 7.5 Hz, 2H), 7.58 – 7.48 (m, 6H). 13 C NMR (101 MHz, CDCl3) δ196.0, 141.9, 140.9, 138.3, 137.5, 134.1, 132.1, 131.8, 130.4, 129.8, 128.5,127.4, 125.9, 124.7, 123.8, 123.0, 121.6. HRMS (ESI): [M+H] + Calculated value: C19H12OS: 289.0682; Measured value: 289.0672. MIR (cm) -1 ):3060, 2922, 1644, 1320, 1094, 666.

[0132] Example 38 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 5-iodo-methylpyrazole, resulting in: 1-Methylpyrazole-5-benzophenone

[0133] Separation yield: 45%, colorless oily substance.

[0134] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.88 (dd, J = 8.3, 1.4 Hz, 2H), 7.67 – 7.56 (m, 2H), 7.56 – 7.44 (m, 3H), 4.22 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 186.1, 138.2, 137.5, 133.1, 129.6, 128.6, 113.8, 39.9. HRMS (ESI): [M+H] + Calculated value: C11H10ON2: 187.0866; Measured value: 187.0854. MIR (cm) -1 ):2924, 2202, 1642,1178, 894, 712.

[0135] Example 39 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 3-iodopyridine, resulting in: Phenylacetone-3-pyridinemethyl ketone

[0136] Separation yield: 48%, colorless oily substance.

[0137] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 8.98 (dd, J = 2.3, 0.9 Hz, 1H), 8.80 (dd, J = 4.9, 1.7 Hz, 1H), 8.11 (dt, J = 7.8, 2.0 Hz, 1H), 7.80 (dd, J =8.3, 1.4 Hz, 2H), 7.67 – 7.57 (m, 1H), 7.50 (t, J = 7.7 Hz, 2H), 7.44 (dd, J= 8.0, 4.9 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 195.0, 152.9, 151.0, 137.3,136.8, 133.3, 130.1, 128.7, 123.5. HRMS (ESI): [M+H] + Calculated value: C12H9ON: 184.0757; Measured value: 184.0753.

[0138] Example 40 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of iodocyclohexane, resulting in: Cyclohexylphenyl ketone

[0139] Separation yield: 60%, colorless oily substance.

[0140] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.94 (d, J = 7.5 Hz, 2H), 7.68 –7.40 (m, 3H), 3.26 (tt, J = 11.5, 3.3 Hz, 1H), 2.00 – 1.80 (m, 4H), 1.74 (d,J = 12.9 Hz, 1H), 1.58 – 1.22 (m, 5H). 13 C NMR (101 MHz, CDCl3) δ 204.0, 136.4,132.8, 128.7, 128.4, 45.7, 29.5, 26.1, 26.0. HRMS (ESI): [M+H] + Calculated value: C13H16O: 189.1274; Measured value: 189.1270.

[0141] Example 41 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 3-phenyliodopropane, resulting in: 1,4-Diphenyl-1-Butanone

[0142] Separation yield: 49%, colorless oily substance.

[0143] Characterization data: 1H NMR (400 MHz, CDCl3) δ 7.97 – 7.90 (m, 2H), 7.55 (t, J =7.3 Hz, 1H), 7.45 (t, J = 7.6 Hz, 2H), 7.30 (t, J = 7.5 Hz, 2H), 7.27 – 7.17(m, 3H), 2.99 (t, J = 7.3 Hz, 2H), 2.73 (t, J = 7.6 Hz, 2H), 2.10 (p, J = 7.4Hz, 2H). 13 C NMR (101 MHz, CDCl3) δ 200.3, 141.8, 137.1, 133.1, 128.6, 128.5,128.1, 126.1, 37.8, 35.3, 25.8. HRMS (ESI): [M+H] + Calculated value: C16H16O: 225.1274; Measured value: 225.1278.

[0144] Example 42 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of CF3I, resulting in: 2,2,2-Trifluoro-1-phenylethyl ketone

[0145] Separation yield: 25%, colorless oily substance.

[0146] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 8.06 (d, J = 1.3 Hz, 2H), 7.71 (t,J = 7.5 Hz, 1H), 7.58 – 7.51 (m, 2H). 13 C NMR (101 MHz, CDCl3) δ 180.8 (q, J =35.0 Hz), 135.6, 130.2 (q, J = 2.1 Hz), 129.9, 129.2, 118.2 (q, J = 291.3Hz). 19 F NMR (376 MHz, CDCl3) δ -71.37.

[0147] Example 43 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of iodoethane, resulting in: Phenylacetone

[0148] Separation yield: 30%, white solid.

[0149] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 7.0 Hz, 2H), 7.55 (t,J = 7.4 Hz, 1H), 7.45 (t, J = 7.6 Hz, 2H), 3.00 (q, J = 7.2 Hz, 2H), 1.23 (t,J = 7.2 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 200.8, 137.0, 132.9, 128.6, 128.0, 31.8, 8.3.

[0150] Example 44 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 4-bromoiodobenzene, resulting in: 4-Bromobenzophenone

[0151] Separation yield: 86%, colorless oily substance.

[0152] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 7.0 Hz, 2H), 7.67 (d,J = 8.6 Hz, 2H), 7.64 – 7.56 (m, 3H), 7.48 (t, J = 7.7 Hz, 2H). 13 C NMR (101MHz, CDCl3) δ 195.8, 137.3, 136.4, 132.8, 131.7, 131.7, 130.1, 128.5, 127.6.HRMS (ESI): [M+H] + Calculated value: C13H9OBr: 260.9910; Measured value: 260.9910.

[0153] Example 45 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 1,4-diiodobenzene, resulting in: 4-Iodobenzophenone

[0154] Separation yield: 81%, colorless oily substance.

[0155] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 8.4 Hz, 2H), 7.77 (d,J = 6.8 Hz, 2H), 7.60 (t, J = 7.4 Hz, 1H), 7.55 – 7.45 (m, 4H). 13 C NMR (101MHz, CDCl3) δ 196.0, 137.7, 137.2, 137.0, 132.8, 131.6, 130.1, 128.5, 100.2.HRMS (ESI): [M+H] + Calculated value: C13H9OI: 308.9770; Measured value: 308.9768.

[0156] Example 46 The preparation steps are the same as in Example 1, except that sodium benzoate is replaced with an equal amount of sodium 4-methylbenzoate, resulting in: 4,4′-Dimethylbenzophenone

[0157] Separation yield: 75%, colorless oily substance.

[0158] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 7.8 Hz, 4H), 7.27 (d,J = 7.4 Hz, 4H), 2.44 (d, J = 3.6 Hz, 6H). 13 C NMR (101 MHz, CDCl3) δ 196.4,143.0, 135.3, 130.3, 129.0, 21.7. HRMS (ESI): [M+H] + Calculated value: C15H14O: 211.1117; Measured value: 211.1110.

[0159] Example 47 The preparation steps are the same as in Example 1, except that sodium benzoate is replaced with an equal amount of sodium 3-methylbenzoate, resulting in: (3-Methylphenyl)(4-methylphenyl) methyl ketone

[0160] Separation yield: 60%, colorless oily substance.

[0161] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 8.2 Hz, 2H), 7.61 (s,1H), 7.56 (d, J = 7.2 Hz, 1H), 7.41 – 7.32 (m, 2H), 7.28 (d, J = 7.9 Hz, 2H),2.43 (d, J = 9.8 Hz, 6H). 13 C NMR (101 MHz, CDCl3) δ 196.9, 143.3, 138.2,138.1, 135.1, 133.0, 130.5, 130.4, 129.0, 128.1, 127.3, 21.8, 21.5. HRMS(ESI): [M+H] + Calculated value: C15H14O: 211.1117; Measured value: 211.1103.

[0162] Example 48 The preparation steps are the same as in Example 1, except that sodium benzoate is replaced with an equal amount of sodium 2-methylbenzoate, resulting in: 2,4'-Dimethylbenzophenone

[0163] Separation yield: 45%, white solid.

[0164] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.71 (d, J = 8.2 Hz, 2H), 7.41 –7.35 (m, 1H), 7.32 – 7.23 (m, 5H), 2.43 (s, 3H), 2.32 (s, 3H). 13 C NMR (101MHz, CDCl3) δ 198.5, 144.2, 139.1, 136.6, 135.2, 131.0, 130.4, 130.1, 129.3,128.4, 125.3, 21.8, 20.0. HRMS (ESI): [M+H] + Calculated value: C15H14O: 211.1117; Measured value: 211.1120.

[0165] Example 49 The preparation steps are the same as in Example 1, except that sodium benzoate is replaced with an equal amount of sodium 4-tert-butylbenzoate, resulting in: 4-tert-butyl-4'-methylbenzophenone

[0166] Separation yield: 70%, colorless oily substance.

[0167] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.77 – 7.71 (m, 4H), 7.49 (d, J =8.5 Hz, 2H), 7.28 (d, J = 7.9 Hz, 2H), 2.44 (s, 3H), 1.37 (s, 9H). 13 C NMR (101MHz, CDCl3) δ 196.4, 156.0, 143.1, 135.3, 135.2, 130.4, 130.1, 129.0, 125.3,35.2, 31.3, 21.8. HRMS (ESI): [M+H] + Calculated value: C18H20O: 253.1587; Measured value: 253.1570. MIR (cm) -1 ): 2960, 1640, 1294, 1020, 796, 684.

[0168] Example 50 The preparation steps are the same as in Example 1, except that sodium benzoate is replaced with an equal amount of sodium 4-dimethylaminobenzoate, resulting in: [4-(dimethylamino)phenyl](4-methylphenyl)methyl ketone

[0169] Separation yield: 46%, pink solid. Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.9 Hz, 2H), 7.65 (d,J = 8.1 Hz, 2H), 7.26 (d, J = 7.8 Hz, 2H), 6.68 (d, J = 9.0 Hz, 2H), 3.07 (s,6H), 2.43 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 195.1, 153.3, 141.8, 136.6,132.7, 129.8, 128.8, 125.2, 110.6, 40.2, 21.7. HRMS (ESI): [M+H] + Calculated value: C16H17ON: 240.1383; Measured value: 240.1385. MIR (cm) -1 ):2922, 1658, 1007, 802.

[0170] Example 51 The preparation steps are the same as in Example 1, except that sodium benzoate is replaced with an equal amount of sodium 4-methylthiobenzoate, resulting in: (4-Methylphenyl)[4-(methylthio)phenyl]methyl ketone

[0171] Separation yield: 62%, colorless oily substance.

[0172] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.71 (dd, J = 17.2, 8.3 Hz, 4H), 7.28 (dd, J = 8.2, 4.7 Hz, 4H), 2.54 (s, 3H), 2.44 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 195.7, 145.0, 143.1, 135.2, 134.1, 130.7, 130.2, 129.1, 124.9, 21.7,15.0. HRMS (ESI): [M+H] + Calculated value: C15H14OS: 243.0838; Measured value: 243.0830. MIR (cm) -1 ):2918, 1645, 1312, 1088, 846, 678.

[0173] Example 52 The preparation steps are the same as in Example 1, except that sodium benzoate is replaced with an equal amount of sodium 4-methoxybenzoate, resulting in: 4-Methoxy-4-methylbenzophenone

[0174] Separation yield: 76%, white solid.

[0175] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 8.9 Hz, 2H), 7.68 (d,J = 8.2 Hz, 2H), 7.27 (d, J = 9.6 Hz, 2H), 6.96 (d, J = 8.9 Hz, 2H), 3.89 (s,3H), 2.44 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 195.4, 163.1, 142.6, 135.5,132.4, 130.5, 130.0, 128.9, 113.5, 55.5, 21.6. HRMS (ESI): [M+H] + Calculated value: C15H14O2: 227.1067; Measured value: 227.1063.

[0176] Example 53 The preparation steps are the same as in Example 1, except that sodium benzoate is replaced with an equal amount of sodium 3,5-dimethoxybenzoate, resulting in: (3,5-Dimethoxyphenyl)(4-Methylphenyl)methyl ketone

[0177] Separation yield: 48%, colorless oily substance.

[0178] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 8.2 Hz, 2H), 7.30 –7.26 (m, 2H), 6.90 (d, J = 2.4 Hz, 2H), 6.66 (t, J = 2.3 Hz, 1H), 3.82 (s,6H), 2.44 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 196.3, 160.6, 143.4, 139.9,134.9, 130.4, 129.1, 107.8, 104.7, 55.7, 21.8. HRMS (ESI): [M+H] + Calculated value: C16H16O3: 257.1172; Measured value: 257.1170. MIR (cm) -1 ):2924, 1660, 1188, 1030, 744.

[0179] Example 54 The preparation steps are the same as in Example 1, except that sodium benzoate is replaced with an equal amount of sodium 4-phenylbenzoate, resulting in: 1,1′-Biphenyl-4-methylbenzophenone

[0180] Separation yield: 41%, colorless oily substance.

[0181] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 8.3 Hz, 2H), 7.76 (d,J = 8.2 Hz, 2H), 7.70 (d, J = 8.3 Hz, 2H), 7.66 (d, J = 7.0 Hz, 2H), 7.48 (d,J = 7.7 Hz, 2H), 7.41 (t, J = 7.3 Hz, 1H), 7.31 (d, J = 8.2 Hz, 2H), 2.46 (s,3H). 13 C NMR (101 MHz, CDCl3) δ 196.2, 145.1, 143.3, 140.2, 136.7, 135.1,130.7, 130.4, 129.1, 129.1, 128.2, 127.4, 127.0, 21.8. HRMS (ESI): [M+H] + Calculated value: C20H16O: 273.1274; Measured value: 273.1269.

[0182] Example 55 The preparation steps are the same as in Example 1, except that sodium benzoate is replaced with an equal amount of sodium 4-fluorobenzoate, resulting in: 4-Fluoro-4-methylbenzophenone

[0183] Separation yield: 92%, colorless oily substance.

[0184] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 4.5 Hz, 2H), 7.68 (d,J = 3.8 Hz, 2H), 7.28 (d, J = 4.6 Hz, 2H), 7.18 – 7.10 (m, 2H), 2.43 (s, 3H).13 C NMR (101 MHz, CDCl3) δ 195.2, 166.6, 164.1 (d, J = 253.5 Hz), 143.5,134.8, 134.2, 132.7 (d, J = 9.1 Hz), 130.3, 129.2, 115.6 (d, J = 21.8 Hz),21.8. 19 F NMR (376 MHz, CDCl3) δ -106.27. HRMS (ESI): [M+H] + Calculated value: C14H11OF: 215.0867; Measured value: 215.0868.

[0185] Example 56 The preparation steps are the same as in Example 1, except that sodium benzoate is replaced with an equal amount of sodium 3-fluorobenzoate, resulting in: (3-Fluorophenyl)(4-Methylphenyl) ketone

[0186] Separation yield: 42%, colorless oily substance.

[0187] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 8.3 Hz, 2H), 7.55 (dt,J = 7.6, 1.3 Hz, 1H), 7.53 – 7.40 (m, 2H), 7.33 – 7.24 (m, 3H), 2.45 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 195.1, 195.0, 163.7 (d, J = 254 Hz), 161.2, 143.7,140.1, 140.0, 134.4 (d, J = 8.8 Hz), 130.3, 129.9, 129.9, 129.1, 125.7,119.3, 119.1, 116.8 (d, J = 21 Hz), 21.7. 19 F NMR (376 MHz, CDCl3) δ -112.15.HRMS (ESI): [M+H] + Calculated value: C14H11OF: 215.0867; Measured value: 215.0870. MIR (cm) -1):2921,1650, 1118, 850, 628.

[0188] Example 57 The preparation steps are the same as in Example 1, except that sodium benzoate is replaced with an equal amount of sodium 2-fluoro-4-methylbenzoate, resulting in: (2-Fluoro-4-methylphenyl)(4-methylphenyl)methyl ketone

[0189] Separation yield: 53%, colorless oily substance.

[0190] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 6.7 Hz, 2H), 7.44 (t,J = 7.6 Hz, 1H), 7.26 (d, J = 7.9 Hz, 2H), 7.06 (d, J = 6.3 Hz, 1H), 6.96 (d,J = 12.4 Hz, 1H), 2.43 (s, 6H). 13 C NMR (101 MHz, CDCl3) δ 193.3, 160.2 (d, J =252 Hz), 144.2, 135.3, 130.9, 130.8 (d, J = 10.1 Hz), 130.3, 130.1, 129.2,125.1 (d, J = 14.2 Hz), 116.9 (d, J = 30 Hz), 21.8, 21.6. 19 F NMR (376 MHz, CDCl3) δ -111.72. HRMS (ESI): [M+H] + Calculated value: C15H13OF: 229.1023; Measured value: 229.1012 MIR (cm²) -1 ): 3012, 1660, 1220, 1108, 758.

[0191] Example 58 The preparation steps are the same as in Example 1, except that sodium benzoate is replaced with an equal amount of sodium 3-fluoro-5-trifluoromethylbenzoate, resulting in: (3-Fluoro-5-trifluoromethylphenyl)(4-methylphenyl)one

[0192] Separation yield: 68%, colorless oily substance.

[0193] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.83 (s, 1H), 7.70 (d, J = 8.1 Hz,2H), 7.67 (d, J = 9.0 Hz, 1H), 7.54 (d, J = 8.2 Hz, 1H), 7.33 (d, J = 8.0 Hz,2H), 2.46 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 193.5, 162.2 (d, J = 252.5 Hz), 144.5, 141.0, 133.5, 130.2, 129.4, 122.4 (q, J = 7.5 Hz), 120.1 (d, J = 20.2Hz), 116.2 (d, J = 20.2, 3.8 Hz), 21.7. 19 F NMR (376 MHz, CDCl3) δ -62.72, -109.23. HRMS (ESI): [M+H] + Calculated value: C15H10OF4: 283.0740; Measured value: 283.0758. MIR (cm) -1 ): 1650, 1445, 1210, 987, 542.

[0194] Example 59 The preparation steps are the same as in Example 1, except that sodium benzoate is replaced with an equal amount of sodium 3,5-difluorobenzoate, resulting in: (3,5-Difluorophenyl)(4-methylphenyl)one

[0195] Separation yield: 61%, colorless oily substance.

[0196] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.71 (d, J = 8.1 Hz, 2H), 7.31 (d,J = 8.0 Hz, 4H), 7.02 (tt, J = 8.5, 2.4 Hz, 1H), 2.45 (s, 3H). 13C NMR (101MHz, CDCl3) δ 193.8, 162.7 (dd, J = 262.6, 10.1 Hz), 144.3, 141.0 (t, J =10.1 Hz), 133.8, 130.3, 129.4, 112.9 (dd, J = 20.2, 3.0 Hz), 107.5 (d, J =30.3 Hz), 21.8. 19 F NMR (376 MHz, CDCl3) δ -108.23. HRMS (ESI): [M+H] + Calculated value: C14H10OF2: 233.0772; Measured value: 233.0786. MIR (cm) -1 ): 3054, 1660, 1120, 878, 750.

[0197] Example 60 The preparation steps are the same as in Example 1, except that sodium benzoate is replaced with an equal amount of sodium 4-trifluoromethylbenzoate, resulting in: 4-(trifluoromethyl)-4'-methylbenzophenone

[0198] Separation yield: 68%, colorless oily substance.

[0199] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 8.1 Hz, 2H), 7.73 (dd,J = 11.0, 8.2 Hz, 4H), 7.31 (d, J = 8.0 Hz, 2H), 2.46 (s, 3H). 13 C NMR (101MHz, CDCl3) δ 195.4, 144.2, 141.2, 134.1 (q, J = 32.6 Hz), 130.4, 130.1,129.3, 125.4 (q, J = 3.7 Hz), 123.7 (q, J = 272.7 Hz), 21.8. 19 F NMR (376 MHz, CDCl3) δ -62.86. HRMS (ESI): [M+H] + Calculated value: C15H11OF3: 265.0835; Measured value: 265.0846.

[0200] Example 61 The preparation steps are the same as in Example 1, except that sodium benzoate is replaced with an equal amount of sodium 3-trifluoromethylbenzoate, resulting in: 3-(trifluoromethyl)-4'-methylbenzophenone

[0201] Separation yield: 68%, colorless oily substance.

[0202] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 8.03 (s, 1H), 7.95 (d, J = 7.7 Hz,1H), 7.83 (d, J = 8.1 Hz, 1H), 7.70 (d, J = 8.2 Hz, 2H), 7.65 – 7.59 (m, 1H),7.30 (d, J = 7.9 Hz, 2H), 2.45 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 195.2,144.1, 138.7, 134.1, 133.1, 131.1 (q, J = 34.0 Hz), 130.4, 129.4, 129.0,128.8 (q, J = 3.4 Hz), 126.8 (q, J = 3.8 Hz), 122.5 (q, J = 272.5 Hz), 21.8. 19 F NMR (376 MHz, CDCl3) δ -62.57. HRMS (ESI): [M+H] + Calculated value: C15H11OF3: 265.0835; Measured value: 265.0835. MIR (cm) -1 ): 2924, 1650, 1330, 958, 696.

[0203] Example 62 The preparation steps are the same as in Example 1, except that sodium benzoate is replaced with an equal amount of sodium 4-trifluoromethoxybenzoate, resulting in: 4-Methylphenyl[4-(trifluoromethoxy)phenyl]one

[0204] Separation yield: 75%, colorless oily substance.

[0205] Characterization data: 1H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 8.8 Hz, 2H), 7.71 (d,J = 8.2 Hz, 2H), 7.34 – 7.28 (m, 4H), 2.49 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ195.1, 152.1, 143.8, 136.3, 134.5, 131.9, 130.3, 129.2, 120.1 (q, J = 257Hz), 21.8. 19 F NMR (376 MHz, CDCl3) δ -57.48. HRMS (ESI): [M+H] + Calculated value: C15H11O2F3: 281.0784; Measured value: 281.0774. MIR (cm) -1 ): 2926, 1658, 1254, 1018,674.

[0206] Example 63 The preparation steps are the same as in Example 1, except that sodium benzoate is replaced with an equal amount of sodium 3,5-bis(trifluoromethyl)benzoate, resulting in: 3,5-Di(trifluoromethyl)phenyl ketone

[0207] Separation yield: 63%, colorless oily substance.

[0208] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 8.21 (s, 2H), 8.08 (s, 1H), 7.70 (d, J = 7.9 Hz, 2H), 7.35 (d, J = 7.9 Hz, 2H), 2.48 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 193.3, 144.8, 139.8, 133.3, 132.1 (q, J = 34.1 Hz), 130.2, 129.8,129.6, 125.4 (m, J = 3.8 Hz), 124.3, 121.6, 21.8. 19 F NMR (376 MHz, CDCl3) δ -62.78. HRMS (ESI): [M+H] +Calculated value: C16H10OF6: 333.0709; Measured value: 333.0705. MIR (cm) -1 ): 1668, 1580, 1318, 1198, 698.

[0209] Example 64 The preparation steps are the same as in Example 1, except that sodium benzoate is replaced with an equal amount of sodium 4-chlorobenzoate, resulting in: 4-Chloro-4'-methylbenzophenone

[0210] Separation yield: 65%, colorless oily substance.

[0211] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.81 (dd, J = 8.8, 5.4 Hz, 2H), 7.68 (d, J = 8.1 Hz, 2H), 7.28 (d, J = 7.9 Hz, 2H), 7.14 (t, J = 8.7 Hz, 2H), 2.43 (s, 3H). 13 C14H11OCl (101 MHz, CDCl3) δ 195.2, 166.6, 164.1, 143.5, 134.9, 132.7, 130.3, 129.2, 115.6, 115.4, 21.8. HRMS (ESI): [M+Li]+ Calculated value: C14H11OCl: 237.0653; Measured value: 237.0653.

[0212] Example 65 The preparation steps are the same as in Example 1, except that sodium benzoate is replaced with an equal amount of sodium 5-bromo-2-chlorobenzoate, resulting in: (5-Bromo-2-chlorophenyl)(4-methylphenyl)methyl ketone

[0213] Separation yield: 60%, colorless oily substance.

[0214] Characterization data: 1H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 8.2 Hz, 2H), 7.53 (dd,J = 8.6, 2.4 Hz, 1H), 7.48 (d, J = 2.3 Hz, 1H), 7.32 (d, J = 8.5 Hz, 1H), 7.27 (d, J = 8.0 Hz, 2H), 2.43 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 193.3,145.4, 140.6, 134.0, 133.5, 131.8, 131.6, 130.4, 129.6, 120.6, 21.9. HRMS(ESI): [M+H] + Calculated value: C14H10OBrCl: 308.9676; Measured value: 308.9685. MIR (cm -1 ): 2920,1667, 1134, 815, 512.

[0215] Example 66 The preparation steps are the same as in Example 1, except that sodium benzoate is replaced with an equal amount of sodium tert-valerate, resulting in: 2,2-Dimethyl-1-(4-methylphenyl)-1-propanone

[0216] Separation yield: 42%, colorless oily substance.

[0217] Alternatively, by increasing both 4-iodotoluene (0.4 mmol, 2.0 equiv) and calcium granules (0.3 mmol, 1.5 equiv) to 3.0 equiv and replacing sodium benzoate with an equal amount of tert-valeric acid, the same 2,2-dimethyl-1-(4-methylphenyl)-1-propanone product was obtained.

[0218] Separation yield: 32%, colorless oily substance.

[0219] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 8.2 Hz, 2H), 7.20 (d,J = 8.0 Hz, 2H), 2.38 (s, 3H), 1.35 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 208.5,141.6, 135.5, 128.8, 128.4, 44.2, 28.3, 21.5. HRMS (ESI): [M+H] + Calculated value: C12H16O: 177.1274; Measured value: 177.1256.

[0220] Example 67 The preparation steps are the same as in Example 1, except that sodium benzoate is replaced with an equal amount of sodium cyclopentaneformate, resulting in: Cyclopentyl(4-methylphenyl) ketone

[0221] Separation yield: 45%, colorless oily substance.

[0222] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 7.9 Hz, 2H), 7.18 (d,J = 7.8 Hz, 2H), 3.62 (p, J = 7.9 Hz, 1H), 2.33 (s, 3H), 1.83 (q, J = 6.8 Hz,4H), 1.71 – 1.52 (m, 4H). 13 C NMR (101 MHz, CDCl3) δ 202.6, 143.5, 134.5, 129.3,128.7, 46.3, 30.1, 26.4, 21.7. HRMS (ESI): [M+H] + Calculated value: C13H16O: 189.1274; Measured value: 189.1271.

[0223] Example 68 The preparation steps are the same as in Example 1, except that sodium benzoate is replaced with an equal amount of sodium cyclohexaneformate, resulting in: Cyclohexyl(4-methylphenyl) ketone

[0224] Separation yield: 62%, colorless oily substance.

[0225] Alternatively, by increasing both 4-iodotoluene (0.4 mmol, 2.0 equiv) and calcium granules (0.3 mmol, 1.5 equiv) to 3.0 equiv and replacing sodium benzoate with an equal amount of cyclohexanecarboxylic acid, the same cyclohexyl(4-methylphenyl) methyl ketone product was obtained.

[0226] Separation yield: 55%, colorless oily substance.

[0227] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 8.2 Hz, 2H), 7.24 (d,J = 7.8 Hz, 2H), 3.23 (tt, J = 11.5, 3.3 Hz, 1H), 2.39 (s, 3H), 1.85 (d, J =3.3 Hz, 4H), 1.72 (d, J = 14.0 Hz, 1H), 1.55 – 1.18 (m, 5H). 13 C NMR (101 MHz, CDCl3) δ 203.7, 143.6, 133.9, 129.4, 128.5, 45.6, 29.6, 26.1, 26.0, 21.7.HRMS (ESI): [M+H] + Calculated value: C14H18O: 203.1430; Measured value: 203.1419.

[0228] Example 69 The preparation steps are the same as in Example 1, except that sodium benzoate is replaced with an equal amount of sodium 4-fluorobenzoate, and 4-iodotoluene is replaced with an equal amount of 4-fluoroiodobenzene, to obtain a key intermediate in the synthesis of the antihistamine flunarizine, which is also the main monomer raw material for the production of polyetheretherketone (PEEK): 4,4′-Difluorobenzophenone

[0229] Separation yield: 85%, white solid.

[0230] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.81 (dd, J = 8.7, 5.4 Hz, 4H), 7.17 (t, J = 8.5 Hz, 4H). 13C NMR (101 MHz, CDCl3) δ 193.9, 165.5 (d, J = 262.2Hz), 133.8 (d, J = 3.1 Hz), 132.6 (d, J = 9.1 Hz), 115.7 (d, J = 30.3 Hz). 19 FNMR (376 MHz, CDCl3) δ -105.63. HRMS (ESI): [M+H] + Calculated value: C13H8OF2: 219.0616; Measured value: 219.0612.

[0231] Example 70 The preparation steps are the same as in Example 1, except that sodium benzoate is replaced with an equal amount of sodium 5-bromo-2-chlorobenzoate, and 4-iodotoluene is replaced with an equal amount of 4-ethoxyiodobenzene, to obtain the key synthetic intermediate for the diabetes drug dapagliflozin: (5-Bromo-2-chlorophenyl)(4-ethoxyphenyl) methyl ketone

[0232] Separation yield: 72%, white solid.

[0233] Characterization data: 1 H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.9 Hz, 2H), 7.53 (dd,J = 8.5, 2.4 Hz, 1H), 7.48 (d, J = 2.4 Hz, 1H), 7.32 (d, J = 8.5 Hz, 1H), 6.93 (d, J = 8.9 Hz, 2H), 4.11 (q, J = 6.9 Hz, 2H), 1.45 (t, J = 7.0 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 192.2, 164.0, 140.8, 133. 8, 132.7, 131.6, 131.5,130.2, 128.7, 120.6, 114.6, 64.0, 14.7. HRMS (ESI): [M+H] + Calculated value: C15H12O2BrCl: 338.9782; Measured value: 338.9780.

[0234] Example 71 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 4-phenyliodobutane to obtain a pharmacologically active natural product. 1,5-Diphenyl-1-pentanone

[0235] Separation yield: 61%, white solid.

[0236] Characterization data: 1 H NMR (400 MHz, CDCl3)δ 7.95 (d, J = 7.5 Hz, 2H), 7.56 (t, J= 7.4 Hz, 1H), 7.46 (t, J = 7.7 Hz, 2H), 7.31 – 7.26 (m, 2H), 7.20 (d, J =7.1 Hz, 3H), 3.00 (t, J = 7.1 Hz, 2H), 2.68 (t, J = 7.4 Hz, 2H), 1.86 – 1.78(m, 2H), 1.76 – 1.67 (m, 2H). 13 C NMR (101 MHz, CDCl3) δ 200.4, 142.4, 137.1,133.0, 128.7, 128.5, 128.4, 128.1, 125.9, 38.5, 35.9, 31.2, 24.1. HRMS (ESI):[M+Li] + Calculated value: C17H18O: 245.1512; Measured value: 245.1516.

[0237] Example 72 The preparation steps are the same as in Example 1, except that 4-iodotoluene is replaced with an equal amount of 4-(2-chloroethoxy)iodobenzene to obtain the key synthetic intermediate of tamoxifen: [4-(2-chloroethoxy)phenyl]phenyl methyl ketone

[0238] Separation yield: 50%, white solid.

[0239] Characterization data: 1H NMR (400 MHz, CDCl3)δ 7.83 (d, J = 8.9 Hz, 2H), 7.76 (d, J= 6.8 Hz, 2H), 7.57 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.5 Hz, 2H), 6.98 (d, J= 8.8 Hz, 2H), 4.32 (t, J = 5.8 Hz, 2H), 3.86 (t, J = 5.8 Hz, 2H). 13 C NMR (101MHz, CDCl3)δ 195.6, 161.8, 138.2, 132.7, 132.1, 130.9, 129.9, 128.3, 114.2,68.2, 41.7. HRMS (ESI): [M+H] + Calculated value: C15H13O2Cl: 261.0677; Measured value: 261.0675.

[0240] Comparative Example 1 In a nitrogen-filled glove box, sodium benzoate (0.2 mmol), 4-iodotoluene (0.4 mmol), and calcium particles (0.3 mmol) were added to a Schlenk tube, followed by 2 mL of 2-MeTHF (approximately 0.1 M). The mixture was magnetically stirred at 800 rpm at room temperature. After 1 h of stirring, the reaction system showed no significant changes. Samples were taken under nitrogen atmosphere and quenched, but the target product was not detected by TLC. After 12 h, only trace amounts of the target product were detected, and unreacted calcium metal was still visible. This control demonstrates that ordinary solution stirring is insufficient for continuous renewal of the calcium surface, while mechanochemical ball milling significantly promotes calcium insertion and subsequent ketogenesis.

[0241] Comparative Example 2 The preparation steps were the same as in Example 1, except that 2-MeTHF was not added and 4-methylbenzophenone was not obtained by LC-MS detection.

[0242] Comparative Example 3 The preparation steps were the same as in Example 1, except that the calcium particles (0.3 mmol, 1.5 equiv) were replaced with lithium metal (0.3 mmol, 1.5 equiv) to obtain 4-methylbenzophenone with an NMR yield of 58%.

[0243] Comparative Example 4 The preparation steps were the same as in Example 1, except that the calcium particles (0.3 mmol, 1.5 equiv) were replaced with metallic magnesium (0.3 mmol, 1.5 equiv) to obtain 4-methylbenzophenone with an NMR yield of 35%.

[0244] Comparative Example 5 The preparation steps were the same as in Example 1, except that the calcium particles (0.3 mmol, 1.5 equiv) were replaced with strontium metal (0.3 mmol, 1.5 equiv) to obtain 4-methylbenzophenone with an NMR yield of 25%.

[0245] In Example 1 of this invention, using sodium benzoate and 4-iodotoluene as representative substrates, a high yield of the target ketone can be obtained under mechanical ball milling conditions assisted by calcium metal and 2-methyltetrahydrofuran; the NMR yield of the model reaction can reach approximately 95%, and the separation yield can reach approximately 91%. No obvious tertiary alcohol byproducts due to overaddition were observed in Example 1, indicating that this system can effectively suppress secondary nucleophilic addition of ketone products, distinguishing it from highly reactive organometallic systems such as organolithium and Grignard reagents.

[0246] Compared to Example 1, in Comparative Example 1, under ordinary solution stirring conditions, no target product was detected after 1 hour of reaction, and even after extending the reaction to 12 hours, only trace amounts of product were detected, and the calcium metal was not completely consumed. In contrast, in Example 1, the target product 4-methylbenzophenone was obtained stably with a 91% separation yield after approximately 60 minutes of ball milling. These results indicate that the mechanical ball milling in this invention is not a simple replacement of conventional process conditions, but rather a necessary technical means to overcome the passivation of the calcium metal surface and achieve the reaction.

[0247] Compared with Example 1, Comparative Example 2 and Examples 3-7 did not add 2-MeTHF or replaced it with THF, DME, diethyl ether, 2,5-dimethyltetrahydrofuran, and MTBE, respectively. The model reactions had no yield or the yield decreased, indicating that 2-MeTHF has a better effect as a liquid-assisted grinding additive in the system of the present invention.

[0248] Compared to Example 1, replacing Ca with Li, Mg, or Sr in Comparative Examples 3-5, respectively, significantly reduced the model reaction yield, indicating that the results obtained in this invention cannot be expected through conventional metal screening. In particular, although metals such as lithium and magnesium are generally considered to form highly reactive carbon nucleophiles in organometallic chemistry, they do not achieve comparable effects to calcium in the system of this invention, demonstrating the unique characteristics of calcium in this system.

[0249] Compared with Example 1, in Examples 11 and 12, sodium benzoate was replaced with potassium benzoate and lithium benzoate, respectively, and the yield of the model reaction decreased, indicating that sodium carboxylate salt has a better effect as carboxylate salt in the system of the present invention, followed by potassium carboxylate salt.

[0250] In summary, compared with the prior art, the beneficial effects of the present invention include: (1) Reduce the use of corrosive reagents: The present invention uses carboxylate, especially sodium carboxylate, as the acyl source; or carboxylic acid can be used directly, and excess calcium can be used to simultaneously complete the consumption of acid protons and the generation and reaction of organic calcium, without the need to pre-convert carboxylic acid into highly reactive derivatives such as acyl chloride, acid anhydride, activated ester or Weinreb amide, thereby shortening the process steps and reducing the use of corrosive or hazardous reagents.

[0251] (2) Avoid the use of sensitive reagents: Organic calcium species are generated in situ by reacting calcium metal with organic halides under ball milling conditions. There is no need to prepare, separate or store highly active organometallic reagents such as organolithium and organomagnesium that are sensitive to air and moisture in advance, which improves the ease of operation and safety.

[0252] (3) Formation of organic calcium species: In a complex system in which organic halides, calcium metal and carboxylates and / or carboxylic acids coexist, untreated or commercial calcium metal is directly activated by mechanochemistry. Fresh calcium surfaces are continuously exposed by impact and shearing, which enables calcium metal to be effectively activated and forms organic calcium species that can participate in acylation reactions in situ, thus overcoming the low reactivity problem caused by calcium surface passivation.

[0253] (4) High selectivity: The organic calcium species react with carboxylates and / or carboxylic acids to form a tetrahedral intermediate that is coordinated with calcium, which inhibits the further attack of the generated ketone product by the organometallic intermediate and avoids the generation of overaddition byproducts such as tertiary alcohols.

[0254] (6) Low solvent consumption: The present invention adopts liquid-assisted grinding method, which only requires a small amount of liquid-assisted grinding additive to enable solid carboxylate and / or carboxylic acid, metallic calcium and organic halide to fully contact and react effectively. Compared with traditional solution reaction, the amount of organic solvent used is significantly reduced, which has the potential for green synthesis and process scale-up.

[0255] (7) Good substrate applicability: This invention is applicable to a variety of aryl, heteroaryl and some alkyl organohalides, as well as a variety of aromatic, heteroaromatic, aliphatic and alkynyl substituted carboxylate salts and / or carboxylic acids; at the same time, it has good compatibility with halogen, alkoxy, halogen-substituted alkyl, halogen-substituted alkoxy, thioether, alkyl-substituted amino, fused ring aromatics and sulfur / oxygen-containing heterocycles.

[0256] (8) High application value: This invention can prepare drug or material-related compounds such as 4,4′-difluorobenzophenone, key diaryl ketone intermediates of dapagliflozin, natural product-related ketones and tamoxifen intermediates in one batch.

[0257] In summary, this invention achieves a combination of high yield, low overaddition, low solvent consumption, and good substrate applicability by generating organic calcium reactive species in situ under specific mechanochemical conditions and using them for the direct selective ketation of carboxylates or carboxylic acids.

[0258] The specific embodiments of the present invention described above do not constitute a limitation on the scope of protection of the present invention. Any other corresponding changes and modifications made in accordance with the technical concept of the present invention should be included within the scope of protection of the claims of the present invention.

Claims

1. A method for synthesizing ketone compounds based on in-situ mechanochemical generation of organic calcium reagents, characterized in that, Includes the following steps: Ketone compounds were obtained by mechanical ball milling of carboxylates and / or carboxylic acids, organohalides, and calcium metals in the presence of liquid-assisted grinding additives, followed by acid quenching and purification. The reaction formulas are as follows: ； In the formula, R 1 It is aryl, heteroaryl, C 1-12 At least one of alkyl and alkynyl substituents, wherein the aryl, heteroaryl, or C 1-12 The alkyl or alkynyl substituent is further optionally coated with one or more halogens, C 1-12 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-12 Alkyl, halogen-substituted C 1-6 Alkoxy, thioether, C 1-3 Alkylthio, C 1-3 Alkyl-substituted amino and phenyl-substituted compounds; R 2 It is aryl, heteroaryl, C 1-12 At least one of the alkyl groups, wherein the aryl, heteroaryl, or C 1-12 The alkyl group is optionally further coated with one or more halogens, C 1-12 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-12 Alkyl, halogen-substituted C 1-6 Alkoxy, thioether, C 1-3 Alkylthio, C 1-3 Alkyl-substituted amino and phenyl-substituted compounds; X is at least one of iodine or bromine; M is at least one of Na, K, and Li.

2. The method for synthesizing ketone compounds based on the in-situ generation of organocalcium reagents using mechanochemical methods according to claim 1, characterized in that, The aryl group is at least one selected from phenyl, naphthyl, anthraceneyl, phenanthryl, and pyrene; and / or, The heteroaryl group is at least one selected from thiophene, benzothiophene, benzofuran, dibenzofuran, dibenzothiophene, pyridine, and pyrazole; and / or, The C 1-12 Alkyl group is C 1-12 Linear alkyl, C 1-12 At least one of the cycloalkyl groups.

3. The method for synthesizing ketone compounds based on the in-situ generation of organocalcium reagents using mechanochemical methods according to claim 1, characterized in that, The carboxylate and / or carboxylic acid are aromatic carboxylic acids, C 1-12 At least one of alkyl carboxylic acids or their corresponding carboxylates; wherein... The aromatic carboxylic acid is an unsubstituted aromatic carboxylic acid, a monosubstituted aromatic carboxylic acid, or a polysubstituted aromatic carboxylic acid; when the aromatic carboxylic acid is a monosubstituted or polysubstituted aromatic carboxylic acid, the substituents on its aromatic ring are each independently selected from halogens, C... 1-12 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-12 Alkyl, halogen-substituted C 1-6 Alkoxy, C 1-3 Alkylthio, C 1-3 Alkyl-substituted amino or phenyl groups; aryl groups selected from at least one of phenyl, naphthyl, anthraceneyl, phenanthryl, and pyreneyl groups; and / or, The C 1-12 Alkyl carboxylic acids are unsubstituted C 1-12 Alkyl carboxylic acids, monosubstituted C 1-12 Alkyl carboxylic acids or polysubstituted C 1-12 Alkyl carboxylic acids; when the C 1-12 Alkyl carboxylic acids are mono- or poly-substituted C. 1-12 In the case of alkylcarboxylic acids, the substituents on the carbon chain or carbon ring are each independently selected from halogens, C... 1-12 Alkyl, C 1-6 Alkoxy, C 1-3 Alkyl-substituted amino or phenyl groups; the alkyl group is selected from at least one linear alkyl or cycloalkyl group; and / or, The carboxylate is at least one of sodium, potassium, and lithium salts.

4. The method for synthesizing ketone compounds based on the in-situ generation of organocalcium reagents using mechanochemical methods according to claim 1, characterized in that, The carboxylate and / or carboxylic acid are selected from at least one of the following compounds or their corresponding carboxylates: 。 5. The method for synthesizing ketone compounds based on the in-situ generation of organocalcium reagents using mechanochemical methods according to claim 1, characterized in that, The organohalides are aryl iodides, aryl bromides, heteroaryl iodides, and C. 1-12 At least one of alkyl iodides; wherein, The aryl iodide is an unsubstituted aryl iodide, a monosubstituted aryl iodide, or a polysubstituted aryl iodide; when the aryl iodide is a monosubstituted or polysubstituted aryl iodide, the substituents on its aromatic ring are each independently selected from halogens, C... 1-12 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-12 Alkyl, halogen-substituted C 1-6 Alkoxy, C 1-3 Alkylthio, C 1-3 Alkyl-substituted amino or phenyl groups; aryl groups selected from at least one of phenyl, naphthyl, anthraceneyl, phenanthryl, and pyreneyl groups; and / or, The aryl bromide is an unsubstituted aryl bromide, a monosubstituted aryl bromide, or a polysubstituted aryl bromide; when the aryl bromide is a monosubstituted or polysubstituted aryl bromide, the substituents on its aromatic ring are each independently selected from halogens, C... 1-12 Alkyl, C 1-6 alkoxy- or halogen-substituted C 1-12 Alkyl, halogen-substituted C 1-6 Alkoxy, C 1-3 Alkylthio, C 1-3 Alkyl-substituted amino or phenyl groups; aryl groups selected from at least one of phenyl, naphthyl, anthraceneyl, phenanthryl, and pyreneyl groups; and / or, The heteroaryl iodide is an unsubstituted heteroaryl iodide, a monosubstituted heteroaryl iodide, or a polysubstituted heteroaryl iodide; when the heteroaryl iodide is a monosubstituted or polysubstituted heteroaryl iodide, the substituents on its heteroaryl ring are each independently selected from halogens, C 1-12 Alkyl, C 1-6 Alkoxy, C 1-3 Alkyl-substituted amino group; heteroaryl group selected from at least one of thienyl, benzothienyl, benzofuranyl, dibenzofuranyl, dibenzothienyl, pyridyl, and pyrazolyl; and / or, The C 1-12 Alkyl iodides are unsubstituted C 1-12 Alkyl iodides, monosubstituted C 1-12 Alkyl iodides or polysubstituted C 1-12 Alkyl iodides; when C 1-12 Alkyl iodides are mono- or poly-substituted C 1-12 In the case of alkyl iodides, the substituents on the carbon chain or carbon ring are each independently selected from halogens, C... 1-12 Alkyl, C 1-6 Alkoxy, C 1-3 Alkyl-substituted amino or phenyl; the alkyl group is selected from at least one of linear alkyl or cycloalkyl groups.

6. The method for synthesizing ketone compounds based on the mechanochemical in-situ generation of organic calcium reagents according to claim 1, characterized in that, The organohalide is selected from at least one of the following compounds: 。 7. The method for synthesizing ketone compounds based on the in-situ generation of organocalcium reagents using mechanochemical methods according to claim 1, characterized in that, The liquid-assisted grinding additive is an ether additive, including but not limited to at least one of 2-methyltetrahydrofuran, tetrahydrofuran, diethyl ether, 2,5-dimethyltetrahydrofuran, methyl tert-butyl ether, and 1,2-dimethoxyethane.

8. The method for synthesizing ketone compounds based on the in-situ generation of organocalcium reagents using mechanochemical methods according to claim 1, characterized in that, Using carboxylates as raw materials, wherein the molar ratio of the carboxylate to calcium metal is 1:(1.0-5.0); and / or, The molar ratio of the carboxylate to calcium metal is 1:(1.2-3.0); and / or, The molar ratio of the carboxylate to calcium metal is 1:1.5; and / or, The molar ratio of the carboxylate to the organohalide is 1:(1.0-5.0); and / or, The molar ratio of the carboxylate to the organohalide is 1:(1.5-3.0); and / or, The molar ratio of the carboxylate to the organohalide is 1:2.0; and / or, The molar ratio of the carboxylate to the liquid-assisted grinding additive is 1:(0.5-20); and / or, The molar ratio of the carboxylate to the liquid-assisted grinding additive is 1:(1.0-8.0); and / or, The molar ratio of the carboxylate to the liquid auxiliary grinding additive is 1:4.

0.

9. The method for synthesizing ketone compounds based on the in-situ generation of organocalcium reagents using mechanochemical methods according to claim 1, characterized in that, The process uses carboxylic acid as a raw material, with a molar ratio of carboxylic acid to calcium metal of 1:(1.5-8.0); and / or, The molar ratio of the carboxylic acid to calcium metal is 1:(2.0-5.0); and / or, The molar ratio of the carboxylic acid to calcium metal is 1:3.0; and / or, The molar ratio of the carboxylic acid to the organohalide is 1:(1.5-8.0); and / or, The molar ratio of the carboxylic acid to the organohalide is 1:(2.0-5.0); and / or, The molar ratio of the carboxylic acid to the organohalide is 1:3.0; and / or, The molar ratio of the carboxylic acid to the liquid-assisted grinding additive is 1:(0.5-20); and / or, The molar ratio of the carboxylic acid to the liquid-assisted grinding additive is 1:(1.0-8.0); and / or, The molar ratio of the carboxylic acid to the liquid-assisted grinding additive is 1:4.

0.

10. The method for synthesizing ketone compounds based on the in-situ generation of organocalcium reagents using mechanochemical methods according to claim 1, characterized in that, The mechanical ball milling process, using carboxylates and / or carboxylic acids, organohalides, and calcium metals as raw materials in the presence of liquid-assisted grinding additives, includes: adding carboxylates and / or carboxylic acids, organohalides, calcium metals, liquid-assisted grinding additives, and grinding balls into a ball mill jar in a protective atmosphere or air; subsequently sealing the ball mill jar; and then performing vibratory grinding in a ball milling apparatus; and / or... During the mechanical ball milling process, the milling frequency is 10-50 Hz, the reaction time is 5-300 min, the reaction temperature is 0-60 ℃, and / or, During the mechanical ball milling process, the milling frequency is 20-40 Hz, and the reaction time is 30-120 min; and / or, During the mechanical ball milling process, the milling frequency is 30 Hz; the reaction time is 60 min; and / or, The acid quenching process includes: quenching the reaction mixture with an acidic aqueous solution; the acidic aqueous solution is dilute hydrochloric acid; the concentration of the acidic aqueous solution is 0.1-6 mol / L; the volume ratio of the carboxylate and / or carboxylic acid to the acidic aqueous solution is 1 mmol : 1-20 mL; and / or, The separation and purification process is at least one of the following: organic solvent extraction, short silica gel column, column chromatography, preparative thin-layer chromatography, crystallization, or recrystallization.

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