Method for synthesizing meta-position secondary alkyl substituted aryl carboxylic acid

Abstract

The invention belongs to the technical field of organic chemistry, and discloses a method for synthesizing meta-position secondary alkyl substituted aryl carboxylic acid. According to the method, in a protective atmosphere, an organic solvent is taken as a reaction medium, aryl carboxylic acid and substituted Katritzky salt react under the action of a ruthenium catalyst, a ligand, an additive and an alkaline compound, and meta-position secondary alkyl substituted aryl carboxylic acid is obtained. According to the invention, meta-position secondary alkyl substituted aryl carboxylic acid is successfully synthesized, and meta-position C-H bond secondary alkylation is realized. The method provided by the invention has the advantages of high yield, wide substrate applicability, cheap and easily-prepared raw materials, simple operation and mild conditions, and is expected to be practically applied to large-scale production.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a method for synthesizing an aryl carboxylic acid substituted with a meta-secondary alkyl group. Background Art

[0002] Carboxylic acids are one of the most common organic compounds and are widely present in various drug molecules. The versatility and interconversion ability of carboxyl groups make organic acids important synthetic precursors for many functional groups (such as alcohols, aldehydes, esters, and amides). Therefore, the synthesis and structural modification of carboxylic acids are extremely important in the fields of chemical applications, pharmaceuticals, and functional materials.

[0003] In the past few decades, transition metal-catalyzed C-H bond activation has become an effective method for functionalization of carboxylic acids. Compared with traditional methods, C-H bond activation does not require pre-activated starting materials, and has high atom economy and step economy. The C-H bond functionalization reaction of aromatic carboxylic acids is mainly concentrated in its ortho position. The carboxyl group has a guiding ability and can coordinate with the transition metal to guide the C-H bond activation of its ortho position to form a relatively stable cyclometallated intermediate, which is then reacted with various coupling reagents to obtain ortho-functionalized products (Weak Coordination as a Powerful Means for Developing Broadly Useful C-H Functionalization Reactions. Acc. Chem. Res. 2012, 45, 788-802; Recent Advances in External-Directing-Group-Free C Functionalization of Carboxylic Acids without Decarboxylation. ACS Catal. 2021, 11, 4205-4229.). However, the preparation of meta-substituted aryl carboxylic acids is still very difficult, because aryl carboxylic acids and metals are difficult to form stable cyclometallic intermediates at the meta position. Recently, it has been reported that aryl carboxylic acid meta-CH bond functionalization is achieved by introducing a template (Pd (II) -catalysed meta-C-H functionalizations of benzoic acid derivatives.Nat.Commun.2016,7,10443; Experimental and Computational Development of aConformationally Flexible Template for the meta-CH Functionalization of Benzoic Acids.J.Am.Chem.Soc.2017,139,10702-10714), but the introduction and removal of the template lead to poor step economy of the reaction, and the method has poor functional group compatibility, and cannot be compatible with functional groups (such as hydroxyl and amino) with certain coordination ability.At present, there is only one report on the functionalization of the meta-CH bond of aryl carboxylic acid directly, which is a reaction between aryl carboxylic acid and α-acyl halide as raw materials to achieve the tertiary alkylation of the CH bond of the meta-position of aryl carboxylic acid (Ligand-Enabled Ruthenium-Catalyzed meta-CH Alkylation of (Hetero) Aromatic Carboxylic Acids. Nat. Commun. 2024, 15, 5552.). However, the reaction is limited to tertiary α-acyl halides. When secondary α-acyl halides are used as reactants, the main result is a nucleophilic substitution reaction between carboxylic acid and α-acyl halide (S). N 2) product.

[0004] Therefore, it is particularly important to develop a method for aromatic carboxylic acids to overcome the nucleophilic substitution reaction and achieve secondary alkylation of their meta-CH bonds. Summary of the invention

[0005] In view of the problems and shortcomings of the prior art, the object of the present invention is to provide a simple and efficient method for synthesizing meta-secondary alkyl-substituted aryl carboxylic acids. The present invention uses abundant, cheap and easily available carboxylic acids and Katritzky salts as raw materials, and a divalent ruthenium complex as a catalyst. With the assistance of ligands, additives and inorganic bases, in an organic solvent, a meta-CH bond secondary alkylation reaction of aryl carboxylic acids and Katritzky salts is achieved to obtain meta-secondary alkyl-substituted carboxylic acid compounds in high yield. The method of the present invention has the advantages of low price, wide substrate applicability, and the synthesized product has potential pharmaceutical value.

[0006] The purpose of the present invention is achieved through the following technical solutions:

[0007] A method for synthesizing a meta-secondary alkyl-substituted aryl carboxylic acid comprises the following steps:

[0008] Under a protective atmosphere, with an organic solvent as the reaction medium, an aryl carboxylic acid is reacted with a substituted Katritzky salt (i.e., an alkyl substituted pyridinium salt) in the presence of a ruthenium catalyst, a ligand, an additive and a basic compound to obtain an meta-secondary alkyl substituted aryl carboxylic acid.

[0009] The structure of the aryl carboxylic acid is Dashed lines indicate looping or non-looping;

[0010] When not forming a ring, R 1 , R 2 , R 3 , R 4each independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, halogen, -OH, substituted or unsubstituted alkoxy, aryl-O-, -NR'R", -NHC(=O)R', -NR'C(=O)R", -RC(=O)NHR', -C(=O)OR', -C(=O)R' or -OSO2R"', wherein R' and R" are H, C1-C6 alkyl, phenyl or benzyl, and R"' is C6-C 10 Aryl or substituted C6-C 10 Aryl. In -NHC(=O)R', R' is not H, in -NR'C(=O)R" R' and R" are not H, in -C(=O)R', R' is not H. In -RC(=O)NHR', R is an alkylene group (preferably a C1-C3 alkylene group), and R' is not H.

[0011] The alkyl group is C1-C 20 Alkyl (preferably C1-C6 alkyl); the alkoxy group is C1-C 20 Alkoxy (preferably C1-C6 alkoxy); the aryl group is C6-C 20 Aryl (preferably C6-C 10 Aryl, such as phenyl, naphthyl);

[0012] The substituted alkyl refers to the replacement of hydrogen on the alkyl by halogen; the substituted alkoxy refers to the replacement of hydrogen on the alkoxy by halogen; the substituted aryl refers to the replacement of hydrogen on the aryl by alkyl, halogen, ester, carbonyl, amine, amide or hydroxyl.

[0013] The aryl in the aryl-O- is an aromatic hydrocarbon group, such as phenyl and naphthyl. 10 Aryl is alkyl substituted C6-C 10 Aryl, halogen substituted C6-C 10 Aryl, etc.

[0014] R 2 and R 4 At least one of them is H.

[0015] Preferably, R 1 , R 2 , R 3 , R 4 2 of them are hydrogen, 3 of them are hydrogen, and 4 of them are hydrogen.

[0016] When 3 are hydrogen atoms, R 1 Not hydrogen or R 3 Not hydrogen or R 4 Not hydrogen.

[0017] When 2 are hydrogen atoms, R 2 and R 4 is hydrogen or R1 and R 2 is hydrogen or R 2 and R 3 is hydrogen or R 3 and R 4 For hydrogen.

[0018] When forming a ring, R 1 and R 2 Ring-forming and fused to a benzene ring or R 3 and R 4 The ring is formed and fused with a benzene ring, and the ring obtained after fusion is benzodioxanyl, methylenedioxybenzene ring, naphthalene ring, substituted naphthalene ring, benzofuran, benzotetrahydrofuran, benzo[b]thiophene, indolyl, substituted indolyl, substituted benzofuranyl;

[0019] The substituted naphthalene ring is a halogen-substituted naphthalene ring; the substituted indolyl group refers to an alkyl-substituted indolyl group, a halogen-substituted phenyl-substituted indolyl group, specifically a 1-alkylindolyl group, a 2-substituted phenylindolyl group, a 2-(halogen-substituted phenyl)1-alkylindolyl group; the substituted benzofuranyl group is a 2-alkylbenzofuranyl group, a 2-(alkoxyphenyl)benzofuranyl group.

[0020] R 1 and R 2 The ring is preferably benzodioxole.

[0021] The structure of the Katritzky salt is

[0022] When not forming a ring, R 5 Selected from C1-C 30 Alkyl (preferably C1-C 20 alkyl), cycloalkyl, substituted alkyl, ester group (such as: COOR'); substituted alkyl means that the hydrogen or carbon on the alkyl is replaced by cycloalkyl, CbzHN-, phenyl, substituted phenyl; the substituted phenyl is hydroxy substituted phenyl, benzyloxy substituted phenyl,

[0023] R 6 It is one of -C(=O)OR' or -C(=O)NR'R", wherein R' is C1-C6 alkyl or benzyl; and R" is H, C1-C6 alkyl, phenyl or benzyl.

[0024] R 5 With R 6 Can be connected together to form a ring, X is selected from one of OTf, PF6 or BF4.

[0025] The protective gas is nitrogen or argon.

[0026] The alkaline compound is selected from potassium acetate, sodium acetate, cesium acetate, potassium carbonate, potassium phosphate, potassium pivalate, cesium pivalate, sodium pivalate, sodium carbonate, cesium carbonate, potassium tert-butoxide, sodium tert-butoxide, preferably potassium acetate.

[0027] The ruthenium catalyst is diiodide (p-cymene) ruthenium (II) dimer or dichloro (p-cymene) ruthenium (II) dimer.

[0028] The organic solvent is one of 1,4-dioxane, tert-butanol, 1,1,1,3,3,3-hexafluoro-2-propanol (hexafluoroisopropanol) or a mixed solvent of two of them, preferably a mixed solvent in which the volume ratio of tert-butanol to hexafluoroisopropanol is 4:1-20:1.

[0029] The ligand is selected from 2,2'-bipyridine, 5,5'-dimethyl-2,2'-bipyridine, 4,4'-di-tert-butyl-2,2'-bipyridine, 4,4'-dimethyl-2,2'-bipyridine, 4,4'-diphenyl-2,2'-bipyridine, 4,4'-dimethoxy-2,2'-bipyridine, 1,10-phenanthroline, 4,7-dimethoxy-1,10-phenanthroline, 3,4,7,8-tetramethyl -1,10-phenanthroline, 4,7-diphenyl-1,10-phenanthroline, 2-(5-tert-butyl-1H-3-pyrazolyl)pyridine, one of triphenylphosphine, preferably one of 2,2'-bipyridine, 5,5'-dimethyl-2,2'-bipyridine, 4,4'-di-tert-butyl-2,2'-bipyridine, 4,4'-dimethyl-2,2'-bipyridine, 4,4'-diphenyl-2,2'-bipyridine.

[0030] The additive is selected from lithium chloride and lithium trifluoromethanesulfonate.

[0031] The reaction temperature is 70-120° C., and the reaction time is 4-16 hours.

[0032] The reaction molar ratio of the carboxylic acid to the Katritzky salt is (1.5-3): 1. The molar ratio of the ruthenium catalyst to the Katritzky salt is (0.025-0.05): 1. The molar ratio of the ligand to the Katritzky salt is (0.05-0.10): 1, the molar ratio of the additive to the Katritzky salt is (0.10-1): 1, and the molar ratio of the basic compound to the Katritzky salt is (1-3): 1.

[0033] After the reaction is completed, subsequent treatment is performed; the subsequent treatment refers to cooling, adding dilute acid to the system pH = 0.5-1.5, extraction, removal of the solvent in the organic phase, separation and purification. The extraction is ethyl acetate extraction. The separation is column chromatography separation.

[0034] The removal of the solvent in the organic phase refers to removing water and organic solvent in the organic phase. The removal of water in the organic phase refers to drying with a desiccant, the desiccant is anhydrous magnesium sulfate, and then filtering; the removal of the organic solvent in the organic phase refers to removing the organic solvent by reduced pressure distillation.

[0035] The eluent of the column chromatography is a mixed solvent of petroleum ether, ethyl acetate and formic acid, and the volume ratio of petroleum ether to ethyl acetate to formic acid is 120:20:1-80:40:1.

[0036] Alternatively, after the reaction is completed, a methylation treatment is performed, and then a subsequent treatment is performed to obtain a meta-secondary alkyl-substituted aryl carboxylic acid methyl ester compound.

[0037] Specifically, a method for improving the separation efficiency of meta-secondary alkyl-substituted aryl carboxylic acid comprises the following steps: subjecting the above-mentioned product containing meta-secondary alkylated aryl carboxylic acid to methylation treatment and subsequent treatment.

[0038] The methylation refers to reacting the meta-secondary alkylated aryl carboxylic acid product with methyl iodide under the action of an alkaline compound using N-methylpyrrolidone as a reaction medium. The reaction temperature is 55 to 65° C. and the reaction time is 2 to 3 hours. Before the methylation treatment, the product containing the meta-secondary alkylated aryl carboxylic acid is treated to remove the reaction solvent.

[0039] The removal of the reaction solvent refers to removing the organic solvent by reduced pressure distillation;

[0040] The subsequent treatment here refers to quenching the reaction, ethyl acetate extraction, removal of the solvent in the organic phase, and column chromatography separation.

[0041] The quenching reaction refers to adding a saturated sodium bicarbonate solution to the reaction system; the removing of the solvent in the organic phase refers to removing water and organic solvent in the organic phase; the removing of water in the organic phase refers to drying with a desiccant, the desiccant is anhydrous magnesium sulfate, and then filtering; the removing of the organic solvent in the organic phase refers to removing the organic solvent by reduced pressure distillation.

[0042] The eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is (3-20):1.

[0043] At this time, the obtained meta-position secondary alkylated aryl carboxylic acid methyl ester compound can restore the carboxyl group by removing the methyl group.

[0044] When R1 is alkyl, halogen, R 2 , R 3 , R 4 is hydrogen or R 3 is alkoxy, aryl-O-, -NHC(=O)R', -C(=O)OR', -C(=O)R' or -OSO2R"', halogen, R 1 , R 2 , R 4 is hydrogen; or R 1 is alkyl, halogen, R 4 is an alkyl group or an alkoxy group, R 2 , R 3 is hydrogen; or R 3 and R 4 The group fused to the benzene ring is a methylenedioxybenzene ring, a halogen-substituted naphthalene ring, benzo[b]thiophene, a substituted indolyl, or a 2-(alkoxyphenyl)benzofuranyl. 1 , R 2 is hydrogen; or R 1 and R 2 The ring is preferably benzodioxole, R 3 , R 4 When hydrogen is used, methylation treatment is performed after the reaction in order to improve the separation efficiency.

[0045] The substituted indolyl refers to an alkyl-substituted indolyl, a halogen-substituted phenyl-substituted indolyl;

[0046] or R 1 , R 2 , R 3 , R 4 is hydrogen, R 6 is one of -C(=O)O-Me or -C(=O)NH-Ph, R 5 In the case of isopropyl or benzyl, methylation treatment is performed after the reaction in order to improve the separation efficiency.

[0047] The chemical reaction equation of the synthesis method of the present invention is: Taking the non-cyclic as an example,

[0048]

[0049] The synthesis method of the present invention has the following advantages and beneficial effects:

[0050] (1) The method of the present invention uses metal ruthenium as a catalyst and a phosphine compound or a nitrogen compound as a ligand, and has the characteristics of high yield and wide substrate applicability. In addition, the present invention uses aromatic carboxylic acid and Katritzky salt as raw materials, and has the advantages of cheap raw materials, easy preparation and simple operation.

[0051] (2) The synthetic method of the present invention has wide substrate adaptability, inexpensive catalysts, and mild conditions, and is therefore expected to be practically applied to large-scale production. BRIEF DESCRIPTION OF THE DRAWINGS

[0052] Figure 1 is the hydrogen spectrum of the target product obtained in Example 1;

[0053] Figure 2 This is the hydrogen spectrum of the target product obtained in Example 20. DETAILED DESCRIPTION

[0054] The present invention is further described in detail below in conjunction with examples, but the embodiments of the present invention are not limited thereto.

[0055] Example 1

[0056]

[0057] Under nitrogen protection, 0.6mmol benzoic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12h, and the heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, wherein the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid with a volume ratio of 120:20:1, and the yield was 86%.

[0058] The structural characterization data of the obtained product are as follows:

[0059] 1 H NMR (500MHz, CDCl3) δ9.56 (s, 1H), 7.98 (s, 1H), 7.94 (d, J = 7.8 Hz, 1H), 7.49 (d, J = 7.8 Hz, 1H), 7.36 (t, J = 7.7 Hz, 1H), 3.74 (q, J = 7.2 Hz, 1H), 3.60 (s, 3H), 1.47 (d, J = 7.2 Hz, 3H). The hydrogen spectrum is shown in Figure 1 shown.

[0060] 13C NMR (126MHz, CDCl3) δ174.5,171.8,141.0,132.9,129.7,129.4,129.0,128.8,52.2,45.2,18.4.

[0061] Example 2

[0062]

[0063] Under nitrogen protection, 0.6 mmol 2-methylbenzoic acid, 0.3 mmol Katritzky salt substituted in the above reaction formula, 0.015 mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03 mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09 mmol lithium chloride, 0.6 mmol potassium acetate, 3 mL of a mixed solvent of tert-butanol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction vessel in sequence, and the mixture was stirred at 80°C for 12 h. The heating and stirring were stopped, and the mixture was cooled to room temperature. The solvent in the reaction solution was then distilled off under reduced pressure, and 1.5 mmol iodomethane and 0.6 mmol potassium carbonate were added, and the mixture was stirred at 60°C for 2 h. After the reaction is completed, the reaction solution is washed with a saturated sodium bicarbonate solution, extracted with ethyl acetate, the organic phases are combined, dried over anhydrous magnesium sulfate, filtered, the solvent is distilled off under reduced pressure, and separated and purified by column chromatography to obtain the target product, the column chromatography eluent used is a mixed solvent of petroleum ether:ethyl acetate in a volume ratio of 20:1, and the yield is 87%.

[0064] The structural characterization data of the obtained product are as follows:

[0065] 1 H NMR (400MHz, CDCl3) δ7.65(d,J=7.7Hz,1H),7.40(d,J=7.7Hz,1H),7.22(t,J=7.8Hz,1H ), 4.08 (q, J = 7.1Hz, 1H), 3.89 (s, 3H), 3.66 (s, 3H), 2.53 (s, 3H), 1.48 (d, J = 7.1Hz, 3H).

[0066] 13 C NMR (101MHz, CDCl3) δ174.9,168.9,140.6,136.2,131.9,129.9,128.5,125.8,51.9,51.9,41.2,18.0,16.1.

[0067] Example 3

[0068]

[0069] Under nitrogen protection, 0.6mmol 2-phenylbenzoic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12h, and the heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, wherein the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid with a volume ratio of 120:20:1, and the yield was 42%.

[0070] The structural characterization data of the obtained product are as follows:

[0071] 1 H NMR (400MHz, CDCl3) δ7.85 (dd, J=7.8, 1.4Hz, 1H), 7.58 (dd, J=7.8, 1.4Hz, 1H), 7.46-7.37 (m, 4H) ,7.30-7.25(m,1H),7.17-7.12(m,1H),3.67(q,J=7.1Hz,1H),3.61(s,3H),1.33(d,J=7.2Hz,3H).

[0072] 13 C NMR (101MHz, CDCl3) δ175.1,172.5,141.8,140.6,138.7,130.7,130.6,129.2,128.9,128.5,127.9,127.8,127.7,127.3,52.0,41.1,19.0.

[0073] Example 4

[0074]

[0075] Under nitrogen protection, 0.6 mmol 2-fluorobenzoic acid, 0.3 mmol Katritzky salt substituted in the above reaction formula, 0.015 mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03 mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09 mmol lithium chloride, 0.6 mmol potassium acetate, 3 mL of a mixed solvent of tert-butanol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12 h. The heating and stirring were stopped, and the mixture was cooled to room temperature. The solvent in the reaction solution was then distilled off under reduced pressure, and 1.5 mmol methyl iodide and 0.6 mmol potassium carbonate were added, and the mixture was stirred at 60°C for 2 h. After the reaction is completed, the reaction solution is washed with a saturated sodium bicarbonate solution, extracted with ethyl acetate, the organic phases are combined, dried over anhydrous magnesium sulfate, filtered, the solvent is distilled off under reduced pressure, and separated and purified by column chromatography to obtain the target product, the column chromatography eluent used is a mixed solvent of petroleum ether:ethyl acetate in a volume ratio of 20:1, and the yield is 63%.

[0076] The structural characterization data of the obtained product are as follows:

[0077] 1 H NMR (400MHz, CDCl3) δ7.87-7.82(m,1H),7.52-7.47(m,1H),7.23-7.15(m,1 H), 4.09 (q, J = 7.2Hz, 1H), 3.94 (s, 3H), 3.69 (s, 3H), 1.53 (d, J = 7.3Hz, 3H).

[0078] 13 C NMR (101MHz, CDCl3) δ173.9, 164.8 (d, J = 3.6Hz), 159.3 (d, J = 260.1Hz), 133.2 (d, J = 5.0Hz), 130.8 (d, J = 1. 4Hz), 129.4 (d, J = 15.7Hz), 123.9 (d, J = 4.5Hz), 118.8 (d, J = 11.1Hz), 52.3, 52.2, 38.1 (d, J = 4.0Hz), 17.4.

[0079] 19 F NMR (376MHz,CDCl3)δ-115.48.

[0080] Example 5

[0081]

[0082] Under nitrogen protection, 0.6 mmol 2-chlorobenzoic acid, 0.3 mmol Katritzky salt substituted in the above reaction formula, 0.015 mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03 mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09 mmol lithium chloride, 0.6 mmol potassium acetate, 3 mL of a mixed solvent of tert-butanol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12 h. The heating and stirring were stopped, and the mixture was cooled to room temperature. The solvent in the reaction solution was then distilled off under reduced pressure, and 1.5 mmol iodomethane and 0.6 mmol potassium carbonate were added, and the mixture was stirred at 60°C for 2 h. After the reaction is completed, the reaction solution is washed with a saturated sodium bicarbonate solution, extracted with ethyl acetate, the organic phases are combined, dried over anhydrous magnesium sulfate, filtered, the solvent is distilled off under reduced pressure, and separated and purified by column chromatography to obtain the target product, the column chromatography eluent used is a mixed solvent of petroleum ether:ethyl acetate in a volume ratio of 20:1, and the yield is 46%.

[0083] The structural characterization data of the obtained product are as follows:

[0084] 1 H NMR (400MHz, CDCl3) δ7.64(d,J=7.8Hz,1H),7.47(d,J=8.1Hz,1H),7.32(t,J=7. 7Hz, 1H), 4.35 (q, J = 7.2Hz, 1H), 3.94 (s, 3H), 3.69 (s, 3H), 1.52 (d, J = 7.2Hz, 3H).

[0085] 13 C NMR (101MHz, CDCl3) δ174.1,166.7,140.1,132.2,131.8,131.1,129.4,126.7,52.5,52.2,42.1,17.5.

[0086] Example 6

[0087]

[0088] Under nitrogen protection, 0.6mmol 3-methylbenzoic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12h, and the heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, wherein the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid with a volume ratio of 120:20:1, and the yield was 71%.

[0089] The structural characterization data of the obtained product are as follows:

[0090] 1 H NMR (500MHz, CDCl3) δ10.32(s,1H),7.86(s,1H),7.84(s,1H),7.37(s,1H),3.78(q,J=7.2Hz,1H),3.68(s,3H),2.41(s,3H),1.53(d,J=7.2Hz,3H).

[0091] 13 C NMR (126MHz, CDCl3) δ174.7,172.2,140.8,138.7,133.6,129.7,129.7,126.6,52.1,45.1,21.2,18.4.

[0092] Example 7

[0093]

[0094] Under nitrogen protection, 0.6mmol 3-methoxybenzoic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12h, and the heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, and the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid with a volume ratio of 80:20:1, and the yield was 76%.

[0095] The structural characterization data of the obtained product are as follows:

[0096] 1 H NMR (400MHz, CDCl3) δ11.09(s,1H),7.72-7.64(m,1H),7.57-7.52(m,1H),7.16-7. 09(m,1H),3.88(s,3H),3.79(q,J=7.2Hz,1H),3.70(s,3H),1.55(d,J=7.2Hz,3H).

[0097] 13 C NMR (101MHz, CDCl3) δ174.4,171.8,159.8,142.3,130.8,122.0,119.6,113.2,55.5,52.2,45.2,18.3.

[0098] Example 8

[0099]

[0100] Under nitrogen protection, 0.6 mmol 4-methoxybenzoic acid, 0.3 mmol Katritzky salt substituted in the above reaction formula, 0.015 mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03 mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09 mmol lithium chloride, 0.6 mmol potassium acetate, 3 mL of a mixed solvent of tert-butanol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12 h. The heating and stirring were stopped, and the mixture was cooled to room temperature. The solvent in the reaction solution was then distilled off under reduced pressure, and 1.5 mmol iodomethane and 0.6 mmol potassium carbonate were added, and the mixture was stirred at 60°C for 2 h. After the reaction is completed, the reaction solution is washed with a saturated sodium bicarbonate solution, extracted with ethyl acetate, the organic phases are combined, dried over anhydrous magnesium sulfate, filtered, the solvent is distilled off under reduced pressure, and separated and purified by column chromatography to obtain the target product, the column chromatography eluent used is a mixed solvent of petroleum ether:ethyl acetate in a volume ratio of 20:1, and the yield is 81%.

[0101] The structural characterization data of the obtained product are as follows:

[0102] 1 H NMR (400MHz, CDCl3) δ7.96 (dd, J=8.6, 2.2Hz, 1H), 7.91 (d, J=2.2Hz, 1H), 6.89 (d, J=8.6Hz ,1H),4.03(q,J=7.2Hz,1H),3.88(s,3H),3.87(s,3H),3.65(s,3H),1.48(d,J=7.3Hz,3H).

[0103] 13 C NMR (101MHz, CDCl3) δ174.8,166.7,160.4,130.4,129.6,129.4,122.6,110.0,55.6,51.8,51.7,39.2,16.9.

[0104] Example 9

[0105]

[0106] Under nitrogen protection, 0.6mmol 4-trifluoromethoxybenzoic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12h, and the heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, and the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid with a volume ratio of 80:20:1, and the yield was 68%.

[0107] The structural characterization data of the obtained product are as follows:

[0108] 1 H NMR (400MHz, CDCl3) δ10.59 (s, 1H), 8.15 (d, J = 2.2Hz, 1H), 8.07 (dd, J = 8.7, 2.2Hz, 1H),7.39-7.31(m,1H),4.11(q,J=7.2Hz,1H),3.69(s,3H),1.55(d,J=7.2Hz,3H).

[0109] 13 C NMR (101MHz, CDCl3) δ173.8, 170.9, 151.0 (d, J = 1.8Hz), 133.1, 131.4, 130.7, 127.7, 120.3 (q, J = 259.7Hz), 119.3 (q, J = 2.0Hz), 52.3, 39.0, 17.4.

[0110] 19 F NMR (376MHz,CDCl3)δ-56.90.

[0111] Example 10

[0112]

[0113] Under nitrogen protection, 0.6 mmol 4-(4-toluenesulfonyloxy)benzoic acid, 0.3 mmol Katritzky salt substituted in the above reaction formula, 0.015 mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03 mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09 mmol lithium chloride, 0.6 mmol potassium acetate, 3 mL of a mixed solvent of tert-butanol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction vessel in sequence, and the mixture was stirred at 80°C for 12 h. The heating and stirring were stopped, and the mixture was cooled to room temperature. The solvent in the reaction solution was then distilled off under reduced pressure, and 1.5 mmol iodomethane and 0.6 mmol potassium carbonate were added, and the mixture was stirred at 60°C for 2 h. After the reaction is completed, the reaction solution is washed with a saturated sodium bicarbonate solution, extracted with ethyl acetate, the organic phases are combined, dried over anhydrous magnesium sulfate, filtered, the solvent is distilled off under reduced pressure, and separated and purified by column chromatography to obtain the target product, the column chromatography eluent used is a mixed solvent of petroleum ether:ethyl acetate in a volume ratio of 10:1, and the yield is 64%.

[0114] The structural characterization data of the obtained product are as follows:

[0115] 1 H NMR (400MHz, CDCl3CDCl3) δ8.07-8.00(m,1H),7.93-7.87(m,1H),7.83-7.75(m,2H),7.36(d,J=8.0Hz,2H), 7.21(d,J=8.6Hz,1H),3.98(q,J=7.2Hz,1H),3.90(s,3H),3.61(s,3H),2.47(s,3H),1.37(d,J=7.2Hz,3H).

[0116] 13 C NMR (101MHz, CDCl3) δ173.7,165.8,150.5,145.9,134.0,132.4,130.3,130.0,129.6,128.9,128.4,121.9,52.3,52.1,38.3,21.6,17.6.

[0117] Embodiment 11

[0118]

[0119] Under nitrogen protection, 0.6 mmol 4-acetamidobenzoic acid, 00.3 mmol Katritzky salt substituted in the above reaction formula, 0.015 mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03 mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09 mmol lithium chloride, 0.6 mmol potassium acetate, and 3 mL of a mixed solvent of tert-butanol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12 h. The heating and stirring were stopped, and the mixture was cooled to room temperature. The solvent in the reaction solution was then distilled off under reduced pressure, and 1.5 mmol iodomethane and 0.6 mmol potassium carbonate were added, and the mixture was stirred at 60°C for 2 h. After the reaction is completed, the reaction solution is washed with a saturated sodium bicarbonate solution, extracted with ethyl acetate, the organic phases are combined, dried over anhydrous magnesium sulfate, filtered, the solvent is distilled off under reduced pressure, and separated and purified by column chromatography to obtain the target product, the column chromatography eluent used is a mixed solvent of petroleum ether:ethyl acetate in a volume ratio of 10:1, and the yield is 51%.

[0120] The structural characterization data of the obtained product are as follows:

[0121] 1 H NMR (400MHz, CDCl3) δ9.01 (s, 1H), 8.05 (d, J = 8.5Hz, 1H), 7.97-7.92 (m, 2H), 3.94 ( q,J=5.8,4.5Hz,1H),3.90(s,3H),3.71(s,3H),2.24(s,3H),1.59(d,J=7.2Hz,3H).

[0122] 13 C NMR (101MHz, CDCl3) δ175.4,168.7,166.4,140.5,129.6,129.5,126.3,123.7,52.7,52.0,41.9,24.5,15.6.

[0123] Example 12

[0124]

[0125] Under nitrogen protection, 0.6mmol 4-phenoxybenzoic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12h, and the heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, wherein the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid with a volume ratio of 80:20:1, and the yield was 77%.

[0126] The structural characterization data of the obtained product are as follows:

[0127] 1 H NMR (400MHz, CDCl3) δ10.44(s,1H),8.14(d,J=2.1Hz,1H),7.98(dd,J=8.6,2.1Hz,1H),7.43-7.38(m,2H),7.23- 7.18(m,1H),7.07-7.03(m,2H),6.84(d,J=8.6Hz,1H),4.17(q,J=7.2Hz,1H),3.67(s,3H),1.62(d,J=7.3Hz,3H).

[0128] 13 C NMR (101MHz, CDCl3) δ174.6,171.7,159.7,155.6,131.4,131.2,130.8,130.0,124.4,124.1,119.6,116.7,52.1,39.7,17.0.

[0129] Embodiment 13

[0130]

[0131] Under nitrogen protection, 0.6mmol 4-trifluoromethylbenzoic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12h, and the heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, and the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid with a volume ratio of 80:20:1, and the yield was 38%.

[0132] The structural characterization data of the obtained product are as follows:

[0133] 1 H NMR (400MHz, CDCl3) δ8.85(s,1H),8.28(s,1H),8.11(d,J=8.1Hz,1H),7.80(d,J=8.2Hz,1H),4.24(q,J=7.1Hz,1H),3.72(s,3H),1.60(d,J=7.1Hz,3H).

[0134] 13 C NMR(101MHz, CDCl3)δ173.9,170.4,140.3,132.9,132.8(q,J=30.3Hz),130.7,1 28.7, 126.3 (q, J = 5.7Hz), 123.7 (q, J = 274.5Hz), 52.4, 40.9 (d, J = 2.4Hz), 19.3.

[0135] 19 F NMR (376MHz, CDCl3) δ-59.56.

[0136] Embodiment 14

[0137]

[0138] Under nitrogen protection, 0.6 mmol 4-benzoylbenzoic acid, 0.3 mmol Katritzky salt substituted in the above reaction formula, 0.015 mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03 mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09 mmol lithium chloride, 0.6 mmol potassium acetate, 3 mL of a mixed solvent of tert-butanol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12 h. The heating and stirring were stopped, and the mixture was cooled to room temperature. The solvent in the reaction solution was then distilled off under reduced pressure, and 1.5 mmol iodomethane and 0.6 mmol potassium carbonate were added, and the mixture was stirred at 60°C for 2 h. After the reaction is completed, the reaction solution is washed with a saturated sodium bicarbonate solution, extracted with ethyl acetate, the organic phases are combined, dried over anhydrous magnesium sulfate, filtered, the solvent is distilled off under reduced pressure, and separated and purified by column chromatography to obtain the target product, the column chromatography eluent used is a mixed solvent of petroleum ether:ethyl acetate in a volume ratio of 10:1, and the yield is 61%.

[0139] The structural characterization data of the obtained product are as follows:

[0140] 1 H NMR(400MHz, CDCl3)δ8.16(d,J=1.6Hz,1H),8.00(dd,J=8.0,1.6Hz,1H),7.82-7.78(m,2H),7.64-7.59(m,1H),7 .50-7.45(m,2H),7.38(d,J=7.9Hz,1H),4.04(q,J=7.1Hz,1H),3.96(s,3H),3.52(s,3H),1.54(d,J=7.1Hz,3H).

[0141] 13 C NMR (101MHz, CDCl3) δ197.4,174.0,166.1,142.5,139.6,136.8,133.7,131.9,130.2,129.1,128.5,128.4,127.5,52.3,51.9,41.2,18.2.

[0142] Embodiment 15

[0143]

[0144] Under nitrogen protection, 0.6 mmol 4-acetylbenzoic acid, 0.3 mmol Katritzky salt substituted in the above reaction formula, 0.015 mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03 mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09 mmol lithium chloride, 0.6 mmol potassium acetate, 3 mL of a mixed solvent of tert-butanol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction vessel in sequence, and the mixture was stirred at 80°C for 12 h. The heating and stirring were stopped, and the mixture was cooled to room temperature. The solvent in the reaction solution was then distilled off under reduced pressure, and 1.5 mmol iodomethane and 0.6 mmol potassium carbonate were added, and the mixture was stirred at 60°C for 2 h. After the reaction is completed, the reaction solution is washed with a saturated sodium bicarbonate solution, extracted with ethyl acetate, the organic phases are combined, dried over anhydrous magnesium sulfate, filtered, the solvent is distilled off under reduced pressure, and separated and purified by column chromatography to obtain the target product, the column chromatography eluent used is a mixed solvent of petroleum ether:ethyl acetate in a volume ratio of 10:1, and the yield is 58%.

[0145] The structural characterization data of the obtained product are as follows:

[0146] 1 H NMR (400MHz, CDCl3) δ8.06 (s, 1H), 8.00 (d, J = 8.1Hz, 1H), 7.70 (d, J = 8.1Hz, 1H), 4. 37(q,J=7.2Hz,1H),3.93(s,3H),3.65(s,3H),2.62(s,3H),1.56(d,J=7.2Hz,3H).

[0147] 13 C NMR (101MHz, CDCl3) δ202.0,174.4,166.0,141.5,139.9,132.6,129.8,128.5,128.0,52.4,52.0,41.3,29.8,17.9.

[0148] Example 16

[0149]

[0150] Under nitrogen protection, 0.6 mmol monomethyl terephthalate, 0.3 mmol Katritzky salt substituted in the above reaction formula, 0.015 mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03 mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09 mmol lithium chloride, 0.6 mmol potassium acetate, 3 mL of a mixed solvent of tert-butanol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction vessel in sequence, and the mixture was stirred at 80°C for 12 h. The heating and stirring were stopped, and the mixture was cooled to room temperature. The solvent in the reaction solution was then distilled off under reduced pressure, and 1.5 mmol iodomethane and 0.6 mmol potassium carbonate were added, and the mixture was stirred at 60°C for 2 h. After the reaction is completed, the reaction solution is washed with a saturated sodium bicarbonate solution, extracted with ethyl acetate, the organic phases are combined, dried over anhydrous magnesium sulfate, filtered, the solvent is distilled off under reduced pressure, and separated and purified by column chromatography to obtain the target product, the column chromatography eluent used is a mixed solvent of petroleum ether:ethyl acetate in a volume ratio of 10:1, and the yield is 42%.

[0151] The structural characterization data of the obtained product are as follows:

[0152] 1 H NMR (400MHz, CDCl3) δ8.06 (s, 1H), 8.03-7.90 (m, 2H), 4.61 (q, J = 7.2Hz, 1H), 3.94 (s, 3H), 3.92 (s, 3H), 3.67 (s, 3H), 1.59 (d, J = 7.2Hz, 3H).

[0153] 13 C NMR (101MHz, CDCl3) δ174.4,167.2,166.0,142.0,133.3,133.3,130.6,129.7,127.9,52.4,52.3,52.0,42.0,18.0.

[0154] Embodiment 17

[0155]

[0156] Under nitrogen protection, 0.6 mmol 4-bromobenzoic acid, 0.3 mmol Katritzky salt substituted in the above reaction formula, 0.015 mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03 mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09 mmol lithium chloride, 0.6 mmol potassium acetate, 3 mL of a mixed solvent of tert-butanol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction vessel in sequence, and the mixture was stirred at 80°C for 12 h. The heating and stirring were stopped, and the mixture was cooled to room temperature. The solvent in the reaction solution was then distilled off under reduced pressure, and 1.5 mmol iodomethane and 0.6 mmol potassium carbonate were added, and the mixture was stirred at 60°C for 2 h. After the reaction is completed, the reaction solution is washed with a saturated sodium bicarbonate solution, extracted with ethyl acetate, the organic phases are combined, dried over anhydrous magnesium sulfate, filtered, the solvent is distilled off under reduced pressure, and separated and purified by column chromatography to obtain the target product, the column chromatography eluent used is a mixed solvent of petroleum ether:ethyl acetate in a volume ratio of 20:1, and the yield is 63%.

[0157] The structural characterization data of the obtained product are as follows:

[0158] 1 H NMR (400MHz, CDCl3) δ7.98 (d, J=2.1Hz, 1H), 7.78 (dd, J=8.3, 2.1Hz, 1H), 7.65 (d, J= 8.3Hz, 1H), 4.25 (q, J = 7.2Hz, 1H), 3.91 (s, 3H), 3.70 (s, 3H), 1.54 (d, J = 7.2Hz, 3H).

[0159] 13 C NMR (101MHz, CDCl3) δ173.8,166.1,140.5,133.1,129.8,129.8,129.5,129.4,52.2,44.6,17.6.

[0160] Embodiment 18

[0161]

[0162] Under nitrogen protection, 0.6 mmol 2,4-dimethylbenzoic acid, 0.3 mmol Katritzky salt substituted in the above reaction formula, 0.015 mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03 mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09 mmol lithium chloride, 0.6 mmol potassium acetate, 3 mL of a mixed solvent of tert-butanol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12 h. The heating and stirring were stopped, and the mixture was cooled to room temperature. The solvent in the reaction solution was then distilled off under reduced pressure, and 1.5 mmol iodomethane and 0.6 mmol potassium carbonate were added, and the mixture was stirred at 60°C for 2 h. After the reaction is completed, the reaction solution is washed with a saturated sodium bicarbonate solution, extracted with ethyl acetate, the organic phases are combined, dried over anhydrous magnesium sulfate, filtered, the solvent is distilled off under reduced pressure, and separated and purified by column chromatography to obtain the target product, the column chromatography eluent used is a mixed solvent of petroleum ether:ethyl acetate in a volume ratio of 20:1, and the yield is 91%.

[0163] The structural characterization data of the obtained product are as follows:

[0164] 1 H NMR (400MHz, CDCl3) δ7.58(d,J=8.0Hz,1H),7.06(d,J=7.9Hz,1H),4.14(q,J=7.2H z,1H),3.86(s,3H),3.66(s,3H),2.43(s,3H),2.32(s,3H),1.47(d,J=7.2Hz,3H).

[0165] 13 C NMR (101MHz, CDCl3) δ175.3,168.8,140.0,139.7,137.0,129.9,128.3,128.3,52.0,51.8,40.2,20.7,17.0,15.3.

[0166] Embodiment 19

[0167]

[0168] Under nitrogen protection, 0.6 mmol 4-methoxy-2-methylbenzoic acid, 0.3 mmol Katritzky salt substituted in the above reaction formula, 0.015 mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03 mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09 mmol lithium chloride, 0.6 mmol potassium acetate, 3 mL of a mixed solvent of tert-butanol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12 h. The heating and stirring were stopped, and the mixture was cooled to room temperature. The solvent in the reaction solution was then distilled off under reduced pressure, and 1.5 mmol iodomethane and 0.6 mmol potassium carbonate were added, and the mixture was stirred at 60°C for 2 h. After the reaction is completed, the reaction solution is washed with a saturated sodium bicarbonate solution, extracted with ethyl acetate, the organic phases are combined, dried over anhydrous magnesium sulfate, filtered, the solvent is distilled off under reduced pressure, and separated and purified by column chromatography to obtain the target product, the column chromatography eluent used is a mixed solvent of petroleum ether:ethyl acetate in a volume ratio of 20:1, and the yield is 81%.

[0169] The structural characterization data of the obtained product are as follows:

[0170] 1 H NMR (400MHz, CDCl3) δ7.79(d,J=8.7Hz,1H),6.74(d,J=8.7Hz,1H),4.04(q,J=7.1H z,1H),3.85(s,3H),3.80(s,3H),3.62(s,3H),2.53(s,3H),1.39(d,J=7.1Hz,3H).

[0171] 13 C NMR (101MHz, CDCl3) δ175.2,168.3,159.3,138.7,130.7,130.2,123.6,107.8,55.4,51.6,37.7,16.5,15.1.

[0172] Embodiment 20

[0173]

[0174] Under nitrogen protection, 0.6 mmol 2-fluoro-4-methoxybenzoic acid, 0.3 mmol Katritzky salt substituted in the above reaction formula, 0.015 mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03 mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09 mmol lithium chloride, 0.6 mmol potassium acetate, 3 mL of a mixed solvent of tert-butanol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12 h. The heating and stirring were stopped, and the mixture was cooled to room temperature. The solvent in the reaction solution was then distilled off under reduced pressure, and 1.5 mmol iodomethane and 0.6 mmol potassium carbonate were added, and the mixture was stirred at 60°C for 2 h. After the reaction is completed, the reaction solution is washed with a saturated sodium bicarbonate solution, extracted with ethyl acetate, the organic phases are combined, dried over anhydrous magnesium sulfate, filtered, the solvent is distilled off under reduced pressure, and separated and purified by column chromatography to obtain the target product, the column chromatography eluent used is a mixed solvent of petroleum ether:ethyl acetate in a volume ratio of 20:1, and the yield is 73%.

[0175] The structural characterization data of the obtained product are as follows:

[0176] 1 H NMR (400MHz, CDCl3) δ7.88 (t, J = 8.6Hz, 1H), 6.73 (dd, J = 9.0, 1.1Hz, 1H), 4.15 (q, J = 7.2Hz, 1H), 3.90 (s, 3H), 3.88 (s, 3H), 3.66 (s, 3H), 1.44 (d, J = 7.2Hz, 3H). The hydrogen spectrum is shown in Figure 2 shown.

[0177] 13 C NMR (101MHz, CDCl3) δ174.0, 164.7 (d, J = 4.1Hz), 161.3 (d, J = 8.7Hz), 160.4 (d, J = 258.6Hz), 131.7 (d, J = 3.3Hz), 118.7(d,J=17.9Hz), 111.4(d,J=11.6Hz), 106.1(d,J=3.1Hz), 56.1, 52.0, 34.2(d,J=3.9Hz), 15.5(d,J=1.4Hz).

[0178] 19 F NMR (376MHz,CDCl3)δ-112.37.

[0179] Embodiment 21

[0180]

[0181] Under nitrogen protection, 0.6mmol 4-chloro-2-fluorobenzoic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and stirred at 80°C for 12h, and heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, and the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid with a volume ratio of 80:20:1, and the yield was 41%.

[0182] The structural characterization data of the obtained product are as follows:

[0183] 1 H NMR (400MHz, DMSO-d6) δ7.78(t,J=8.2Hz,1H),7.44(d,J=8.5Hz,1H),4.31(q,J=7.1Hz,1H),3.61(s,3H),1.38(d,J=7.1Hz,3H).

[0184] 13 C NMR (101MHz, DMSO-d6) δ172.3, 164.4 (d, J = 3.0Hz), 159.5 (d, J = 260.3Hz), 137.8 (d, J = 6.1Hz), 131.2 (d, J = 2.7H z), 128.7 (d, J = 18.1Hz), 125.7 (d, J = 4.0Hz), 119.1 (d, J = 11.7Hz), 52.4, 37.8 (d, J = 2.3Hz), 15.4 (d, J = 1.8Hz).

[0185] 19 F NMR (376MHz,CDCl3)δ-105.34.

[0186] Embodiment 22

[0187]

[0188] Under nitrogen protection, 0.6mmol 3-fluoro-4-bromobenzoic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12h, and the heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, and the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid with a volume ratio of 80:20:1, and the yield was 52%.

[0189] The structural characterization data of the obtained product are as follows:

[0190] 1 H NMR (400MHz, CDCl3) δ9.84 (s, 1H), 7.88 (s, 1H), 7.74 (d, J = 8.3Hz, 1H), 4.29 (q, J = 7.2Hz, 1H), 3.72 (s, 3H), 1.58 (d, J = 7.4Hz, 3H).

[0191] 13 C NMR (101MHz, CDCl3) δ173.5,170.4,158.9(d,J=248.1Hz),142.9,130.4,125.3(d,J =3.0Hz), 118.2 (d, J = 20.8Hz), 116.2 (d, J = 24.8Hz), 52.5, 44.5 (d, J = 2.3Hz), 17.5.

[0192] 19 F NMR (376MHz,CDCl3)δ-101.41.

[0193] Embodiment 23

[0194]

[0195] Under nitrogen protection, 0.6mmol 2-methyl-5-fluorobenzoic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12h, and the heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, wherein the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid with a volume ratio of 80:20:1, and the yield was 80%.

[0196] The structural characterization data of the obtained product are as follows:

[0197] 1 H NMR (400MHz, CDCl3) δ10.44(s,1H),7.59(dd,J=8.8,2.9Hz,1H),7.24(dd,J=9.3,2 .8Hz,1H),4.11(q,J=7.1Hz,1H),3.71(s,3H),2.58(s,3H),1.52(d,J=7.1Hz,3H).

[0198] 13 C NMR (101MHz, CDCl3) δ174.5, 172.7, 160.3 (d, J = 245.2Hz), 143.0 (d, J = 6.6Hz), 133.6 (d, J = 3.5Hz), 131.6 (d, J = 7.3Hz), 118.3 (d, J = 21.8Hz), 116.5 (d, J = 23.1Hz), 52.3, 41.4 (d, J = 1.6Hz), 18.0, 15.8.

[0199] 19 F NMR (376MHz,CDCl3)δ-115.84.

[0200] Embodiment 24

[0201]

[0202] Under nitrogen protection, 0.6mmol 5-hydroxy-2-methylbenzoic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12h, and the heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, wherein the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid with a volume ratio of 60:20:1, and the yield was 82%.

[0203] The structural characterization data of the obtained product are as follows:

[0204] 1 H NMR (400MHz, DMSO-d6) δ12.82(s,1H),9.52(s,1H),6.98(d,J=2.7Hz,1H),6.75(d,J =2.7Hz,1H),4.01(q,J=7.0Hz,1H),3.59(s,3H),2.30(s,3H),1.34(d,J=7.1Hz,3H).

[0205] 13 C NMR (101MHz, DMSO-d6) δ174.6,169.8,155.0,141.9,134.1,125.3,116.6,114.7,52.0,41.0,18.1,15.1.

[0206] Embodiment 25

[0207]

[0208] Under nitrogen protection, 0.6mmol 1,4-benzodioxane-6-carboxylic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12h, and the heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, wherein the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid with a volume ratio of 80:20:1, and the yield was 68%.

[0209] The structural characterization data of the obtained product are as follows:

[0210] 1 H NMR(400MHz, CDCl3)δ9.76(s,1H),7.62-7.59(m,1H),7.58-7.53(m,1H),4.41-4.31( m,2H),4.30-4.25(m,2H),4.02(q,J=7.2Hz,1H),3.69(s,3H),1.51(d,J=7.2Hz,3H).

[0211] 13 C NMR (101MHz, CDCl3) δ174.6,171.5,145.8,143.1,129.6,122.6,121.9,118.4,64.7,63.8,52.1,38.8,17.0.

[0212] Embodiment 26

[0213]

[0214] Under nitrogen protection, 0.6 mmol 3,4-methylenedioxybenzoic acid, 0.3 mmol Katritzky salt substituted in the above reaction formula, 0.015 mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03 mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09 mmol lithium chloride, 0.6 mmol potassium acetate, 3 mL of a mixed solvent of tert-butanol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12 h. The heating and stirring were stopped, and the mixture was cooled to room temperature. The solvent in the reaction solution was then distilled off under reduced pressure, and 1.5 mmol methyl iodide and 0.6 mmol potassium carbonate were added, and the mixture was stirred at 60°C for 2 h. After the reaction is completed, the reaction solution is washed with a saturated sodium bicarbonate solution, extracted with ethyl acetate, the organic phases are combined, dried over anhydrous magnesium sulfate, filtered, the solvent is distilled off under reduced pressure, and separated and purified by column chromatography to obtain the target product, the column chromatography eluent used is a mixed solvent of petroleum ether:ethyl acetate in a volume ratio of 10:1, and the yield is 73%.

[0215] The structural characterization data of the obtained product are as follows:

[0216] 1 H NMR (400MHz, CDCl3) δ7.58 (s, 1H), 7.37 (s, 1H), 6.04 (d, J = 7.7Hz, 2H), 3.91-3.84 (m, 4H), 3.69 (s, 3H), 1.52 (d, J = 7.3Hz, 3H).

[0217] 13 C NMR (101MHz, CDCl3) δ173.6,166.3,149.2,147.5,124.3,124.1,121.5,108.3,101.9,52.1,52.0,39.3,16.8.

[0218] Embodiment 27

[0219]

[0220] Under nitrogen protection, 0.6mmol 2-naphthoic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12h, and the heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, wherein the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid in a volume ratio of 80:20:1, and the yield was 86%.

[0221] The structural characterization data of the obtained product are as follows:

[0222] 1 H NMR (400MHz, DMSO-d6) δ13.19(s,1H),8.56(s,1H),8.17-8.11(m,2H),7.92(s,1H),7.73-7. 67(m,1H),7.65-7.59(m,1H),4.66(q,J=7.0,6.5Hz,1H),3.59(s,3H),1.55(d,J=7.1Hz,3H).

[0223] 13 C NMR (101MHz, DMSO-d6) δ174.6,167.5,137.8,133.0,133.0,130.6,130.3,129.0,127.8,126.8,123.6,123.3,52.1,40.6,18.2.

[0224] Embodiment 28

[0225]

[0226] Under nitrogen protection, 0.6 mmol 6-bromo-2-naphthoic acid, 0.3 mmol Katritzky salt substituted in the above reaction formula, 0.015 mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03 mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09 mmol lithium chloride, 0.6 mmol potassium acetate, 3 mL of a mixed solvent of tert-butanol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction vessel in sequence, and the mixture was stirred at 80°C for 12 h. The heating and stirring were stopped, and the mixture was cooled to room temperature. The solvent in the reaction solution was then distilled off under reduced pressure, and 1.5 mmol iodomethane and 0.6 mmol potassium carbonate were added, and the mixture was stirred at 60°C for 2 h. After the reaction is completed, the reaction solution is washed with a saturated sodium bicarbonate solution, extracted with ethyl acetate, the organic phases are combined, dried over anhydrous magnesium sulfate, filtered, the solvent is distilled off under reduced pressure, and separated and purified by column chromatography to obtain the target product, the column chromatography eluent used is a mixed solvent of petroleum ether:ethyl acetate in a volume ratio of 10:1, and the yield is 79%.

[0227] The structural characterization data of the obtained product are as follows:

[0228] 1 H NMR (400MHz, CDCl3) δ8.47(s,1H),8.29-8.26(m,1H),8.08(d,J=1.6Hz,1H),7.81(dd,J=8.8,1.3H z,1H),7.64-7.59(m,1H),4.44(q,J=7.1Hz,1H),3.98(s,3H),3.69(s,3H),1.70(d,J=7.2Hz,3H).

[0229] 13 C NMR (101MHz, CDCl3) δ174.4,166.6,136.5,134.5,131.8,131.5,130.5,129.9,127.4,125.7,124.8,123.5,52.3,41.0,17.9.

[0230] Embodiment 29

[0231]

[0232] Under nitrogen protection, 0.6mmol 1-benzofuran-5-carboxylic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12h, and the heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, and the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid with a volume ratio of 80:20:1, and the yield was 47%.

[0233] The structural characterization data of the obtained product are as follows:

[0234] 1 H NMR (400MHz, CDCl3) δ8.37(d,J=1.6Hz,1H),8.06(d,J=1.7Hz,1H),7.74(d,J=2.2Hz, 1H), 6.90 (d, J = 2.2Hz, 1H), 4.33 (q, J = 7.2Hz, 1H), 3.72 (s, 3H), 1.69 (d, J = 7.3Hz, 3H).

[0235] 13 C NMR (101MHz, CDCl3) δ174.0,172.3,155.9,146.3,127.6,125.0,124.7,124.6,123.5,107.4,52.3,39.7,17.2.

[0236] Embodiment 30

[0237]

[0238] Under nitrogen protection, 0.6 mmol benzo[b]thiophene-5-carboxylic acid, 0.3 mmol Katritzky salt substituted in the above reaction formula, 0.015 mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03 mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09 mmol lithium chloride, 0.6 mmol potassium acetate, 3 mL of a mixed solvent of tert-butanol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction vessel in sequence, and the mixture was stirred at 80°C for 12 h. The heating and stirring were stopped, and the mixture was cooled to room temperature. The solvent in the reaction solution was then distilled off under reduced pressure, and 1.5 mmol iodomethane and 0.6 mmol potassium carbonate were added, and the mixture was stirred at 60°C for 2 h. After the reaction is completed, the reaction solution is washed with a saturated sodium bicarbonate solution, extracted with ethyl acetate, the organic phases are combined, dried over anhydrous magnesium sulfate, filtered, the solvent is distilled off under reduced pressure, and separated and purified by column chromatography to obtain the target product, the column chromatography eluent used is a mixed solvent of petroleum ether:ethyl acetate in a volume ratio of 10:1, and the yield is 71%.

[0239] The structural characterization data of the obtained product are as follows:

[0240] 1 H NMR (400MHz, CDCl3) δ8.46(d,J=1.5Hz,1H),7.98(d,J=1.6Hz,1H),7.51(d,J=5.5Hz,1H),7. 44(d,J=5.5Hz,1H),4.11(q,J=7.2Hz,1H),3.96(s,3H),3.68(s,3H),1.70(d,J=7.2Hz,3H).

[0241] 13 C NMR (101MHz, CDCl3) δ173.6,167.1,143.7,139.8,134.8,127.1,127.1,125.1,124.5,122.6,52.2,52.1,44.5,17.1.

[0242] Embodiment 31

[0243]

[0244] Under nitrogen protection, 0.6 mmol 1-methyl-5-indolecarboxylic acid, 0.3 mmol Katritzky salt substituted in the above reaction formula, 0.015 mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03 mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09 mmol lithium chloride, 0.6 mmol potassium acetate, 3 mL of a mixed solvent of tert-butanol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction vessel in sequence, and the mixture was stirred at 80°C for 12 h. The heating and stirring were stopped, and the mixture was cooled to room temperature. The solvent in the reaction solution was then distilled off under reduced pressure, and 1.5 mmol iodomethane and 0.6 mmol potassium carbonate were added, and the mixture was stirred at 60°C for 2 h. After the reaction is completed, the reaction solution is washed with a saturated sodium bicarbonate solution, extracted with ethyl acetate, the organic phases are combined, dried over anhydrous magnesium sulfate, filtered, the solvent is distilled off under reduced pressure, and separated and purified by column chromatography to obtain the target product, the column chromatography eluent used is a mixed solvent of petroleum ether:ethyl acetate in a volume ratio of 10:1, and the yield is 72%.

[0245] The structural characterization data of the obtained product are as follows:

[0246] 1 H NMR (400MHz, CDCl3) δ8.28(d,J=1.6Hz,1H),7.86(d,J=1.7Hz,1H),7.03(d,J=3.2Hz,1H),6.58(d, J=3.2Hz,1H),4.64(q,J=7.1Hz,1H),4.11(s,3H),3.93(s,3H),3.69(s,3H),1.69(d,J=7.1Hz,3H).

[0247] 13 C NMR (101MHz, CDCl3) δ174.6,167.9,136.3,132.8,130.1,124.0,122.9,121.8,121.7,102.8,52.2,51.8,39.4,37.3,18.8.

[0248] Embodiment 32

[0249]

[0250] Under nitrogen protection, 0.6mmol 2-hexylbenzofuran-5-carboxylic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12h, and the heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, wherein the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid with a volume ratio of 80:20:1, and the yield was 88%.

[0251] The structural characterization data of the obtained product are as follows:

[0252] 1 H NMR (400MHz, CDCl3) δ11.64(s,1H),8.23(d,J=1.6Hz,1H),7.98(d,J=1.7Hz,1H),6.48(d,J=1.2Hz,1H),4.31(q,J=7.2Hz,1H),3.7 2(s,3H),2.81(t,J=7.6Hz,2H),1.81-1.72(m,2H),1.68(d,J=7.3Hz,3H),1.47-1.38(m,2H),1.38-1.31(m,4H),0.96-0.88(m,3H).

[0253] 13 C NMR (101MHz, CDCl3) δ174.1,172.6,161.4,155.6,129.1,124.2,124.0,123.9,122.2,102.5,52.1,39.6,31.5,28.8,28.3,27.4,22.5,17.3,14.0.

[0254] Embodiment 33

[0255]

[0256] Under nitrogen protection, 0.6 mmol 2-(4-methoxyphenyl)benzofuran-5-carboxylic acid, 0.3 mmol Katritzky salt substituted in the above reaction formula, 0.015 mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03 mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09 mmol lithium chloride, 0.6 mmol potassium acetate, 3 mL of a mixed solvent of tert-butanol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction vessel in sequence, and the mixture was stirred at 80°C for 12 h. The heating and stirring were stopped, and the mixture was cooled to room temperature. The solvent in the reaction solution was then distilled off under reduced pressure, and 1.5 mmol methyl iodide and 0.6 mmol potassium carbonate were added, and the mixture was stirred at 60°C for 2 h. After the reaction is completed, the reaction solution is washed with a saturated sodium bicarbonate solution, extracted with ethyl acetate, the organic phases are combined, dried over anhydrous magnesium sulfate, filtered, the solvent is distilled off under reduced pressure, and separated and purified by column chromatography to obtain the target product, the column chromatography eluent used is a mixed solvent of petroleum ether:ethyl acetate in a volume ratio of 10:1, and the yield is 43%.

[0257] The structural characterization data of the obtained product are as follows:

[0258] 1 H NMR (400MHz, CDCl3) δ8.21(d,J=1.7Hz,1H),7.92(d,J=1.6Hz,1H),7.83-7.78(m,2H),7.04-6.99(m,2 H), 6.95 (s, 1H), 4.35 (q, J = 7.2Hz, 1H), 3.96 (s, 3H), 3.89 (s, 3H), 3.71 (s, 3H), 1.71 (d, J = 7.2Hz, 3H).

[0259] 13 C NMR (101MHz, CDCl3) δ174.1,167.2,160.3,157.3,154.9,129.6,126.5,125 .5,124.1,124.0,122.5,121.8,114.3,100.0,55.3,52.2,52.0,39.8,17.3.

[0260] Embodiment 34

[0261]

[0262] Under nitrogen protection, 0.6 mmol 2-(4-chlorophenyl)-1-methyl-1H-indole-5-carboxylic acid, 0.3 mmol Katritzky salt substituted in the above reaction formula, 0.015 mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03 mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09 mmol lithium chloride, 0.6 mmol potassium acetate, 3 mL of a mixed solvent of tert-butanol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12 h. The heating and stirring were stopped, and the mixture was cooled to room temperature. The solvent in the reaction solution was then distilled off under reduced pressure, and 1.5 mmol iodomethane and 0.6 mmol potassium carbonate were added, and the mixture was stirred at 60°C for 2 h. After the reaction is completed, the reaction solution is washed with a saturated sodium bicarbonate solution, extracted with ethyl acetate, the organic phases are combined, dried over anhydrous magnesium sulfate, filtered, the solvent is distilled off under reduced pressure, and separated and purified by column chromatography to obtain the target product, the column chromatography eluent used is a mixed solvent of petroleum ether:ethyl acetate in a volume ratio of 10:1, and the yield is 85%.

[0263] The structural characterization data of the obtained product are as follows:

[0264] 1 H NMR (400MHz, CDCl3) δ8.28(d,J=1.7Hz,1H),7.93(d,J=1.7Hz,1H),7.49-7.41(m,4H),6.64( s,1H),4.73(q,J=7.1Hz,1H),3.97(s,3H),3.94(s,3H),3.71(s,3H),1.71(d,J=7.1Hz,3H).

[0265] 13 C NMR (101MHz, CDCl3) δ174.5,167.6,143.3,138.6,134.4,130.7,130.5,129 .2,128.7,124.5,122.5,122.4,122.2,104.2,52.2,51.7,39.4,35.0,19.1.

[0266] Embodiment 35

[0267]

[0268] Under nitrogen protection, 0.6mmol 2,3-dimethylbenzoic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12h, and the heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, wherein the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid with a volume ratio of 100:20:1, and the yield was 83%.

[0269] The structural characterization data of the obtained product are as follows:

[0270] 1 H NMR (500MHz, CDCl3) δ10.60(s,1H),7.76(s,1H),7.30(s,1H),3.72(q,J=7.1Hz,1H),3.67(s,3H),2.51(s,3H),2.33(s,3H),1.51(d,J=7.3Hz,3H).

[0271] 13 C NMR (126MHz, CDCl3) δ174.8,174.1,138.6,137.7,137.4,133.1,129.8,127.8,52.1,44.7,20.7,18.3,16.5.

[0272] Embodiment 36

[0273]

[0274] Under nitrogen protection, 0.6mmol 2,3-dimethoxybenzoic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12h, and the heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, and the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid with a volume ratio of 100:20:1, and the yield was 72%.

[0275] The structural characterization data of the obtained product are as follows:

[0276] 1 H NMR (500MHz, CDCl3) δ10.65(s,1H),7.53(s,1H),7.05(s,1H),3.98(s,3H),3.86(s,3H),3.67(q,J=7.2Hz,1H),3.60(s,3H),1.43(d,J=7.3Hz,3H).

[0277] 13 C NMR (126MHz, CDCl3) δ174.3, 165.8, 152.2, 147.3, 137.3 (d, J = 1.9Hz), 122.6 (d, J = 2.7Hz), 122.1, 116.4, 62.0, 56.1, 52.1, 44.9, 18.3.

[0278] Embodiment 37

[0279]

[0280] Under nitrogen protection, 0.6mmol 2-methyl-3-hydroxybenzoic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12h, and the heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, wherein the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid with a volume ratio of 60:20:1, and the yield was 61%.

[0281] The structural characterization data of the obtained product are as follows:

[0282] 1 H NMR (500MHz, DMSO-d6) δ12.76(s,1H),9.64(s,1H),7.11(s,1H),6.89(s,1H),3.71(q,J=7.0Hz,1H),3.58(s,3H),2.27(s,3H),1.35(d,J=7.1Hz,3H).

[0283] 13 C NMR (126MHz, DMSO-d6) δ174.3,169.4,156.1,138.5,133.0,123.7,119.4,116.3,51.9,44.0,18.5,12.7.

[0284] Embodiment 38

[0285]

[0286] Under nitrogen protection, 0.6 mmol 1,3-benzodioxole-4-carboxylic acid, 0.3 mmol Katritzky salt substituted in the above reaction formula, 0.015 mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03 mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09 mmol lithium chloride, 0.6 mmol potassium acetate, 3 mL of a mixed solvent of tert-butanol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12 h. The heating and stirring were stopped, and the mixture was cooled to room temperature. The solvent in the reaction solution was then distilled off under reduced pressure, and 1.5 mmol iodomethane and 0.6 mmol potassium carbonate were added, and the mixture was stirred at 60°C for 2 h. After the reaction is completed, the reaction solution is washed with a saturated sodium bicarbonate solution, extracted with ethyl acetate, the organic phases are combined, dried over anhydrous magnesium sulfate, filtered, the solvent is distilled off under reduced pressure, and separated and purified by column chromatography to obtain the target product, the column chromatography eluent used is a mixed solvent of petroleum ether:ethyl acetate in a volume ratio of 10:1, and the yield is 53%.

[0287] The structural characterization data of the obtained product are as follows:

[0288] 1 H NMR (500MHz, CDCl3) δ7.25 (s, 1H), 6.90 (s, 1H), 6.01 (s, 2H), 3.84 (s, 3H), 3.63-3.58 (m, 4H), 1.40 (d, J = 7.2Hz, 3H).

[0289] 13 C NMR (126MHz, CDCl3) δ174.5,164.7,149.1,147.6,133.9,121.6,112.2,111.5,102.2,52.1,44.8,18.4.

[0290] Embodiment 39

[0291]

[0292] Under nitrogen protection, 0.6mmol 2-methyl-3-(N-phenylisobutyramide)benzoic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12h, and the heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, wherein the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid in a volume ratio of 80:40:1, and the yield was 78%.

[0293] The structural characterization data of the obtained product are as follows:

[0294] 1 H NMR (500MHz, CDCl3) δ9.67(s,1H),7.74(s,1H),7.54(s,1H),7.24(d,J=8.0Hz,2H),7.15(t,J=7.8Hz,2H),6.96(t ,J=7.4Hz,1H),6.88(s,1H),3.72(q,J=7.2Hz,1H),3.61(s,3H),2.40(s,3H),1.59(s,6H),1.47(d,J=7.2Hz,3H).

[0295] 13 C NMR (126MHz, CDCl3) δ176.2,174.6,172.8,143.9,138.1,137.6,137.5,132 .7,129.4,128.8,128.8,124.4,120.4,52.2,48.1,44.9,27.4,18.4,17.6.

[0296] Embodiment 40

[0297]

[0298] Under nitrogen protection, 0.6 mmol benzoic acid, 0.3 mmol Katritzky salt substituted in the above reaction formula, 0.015 mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03 mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09 mmol lithium chloride, 0.6 mmol potassium acetate, 3 mL of a mixed solvent of tert-butanol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction vessel in sequence, and the mixture was stirred at 80°C for 12 h. The heating and stirring were stopped, and the mixture was cooled to room temperature. The solvent in the reaction solution was then distilled off under reduced pressure, and 1.5 mmol iodomethane and 0.6 mmol potassium carbonate were added, and the mixture was stirred at 60°C for 2 h. After the reaction is completed, the reaction solution is washed with a saturated sodium bicarbonate solution, extracted with ethyl acetate, the organic phases are combined, dried over anhydrous magnesium sulfate, filtered, the solvent is distilled off under reduced pressure, and separated and purified by column chromatography to obtain the target product, the column chromatography eluent used is a mixed solvent of petroleum ether:ethyl acetate in a volume ratio of 20:1, and the yield is 59%.

[0299] The structural characterization data of the obtained product are as follows:

[0300] 1 H NMR (400MHz, CDCl3) δ8.01(s,1H),7.95(d,J=7.8Hz,1H),7.57(d,J=7.7Hz,1H),7.40(t,J=7.7Hz,1H),3.92( s,3H),3.66(s,3H),3.24(d,J=10.5Hz,1H),2.45-2.31(m,1H),1.05(d,J=6.5Hz,3H),0.71(d,J=6.8Hz,3H).

[0301] 13 C NMR (101MHz, CDCl3) δ174.0,166.9,138.7,132.9,130.4,129.7,128.5,128.5,59.7,52.1,51.8,31.9,21.3,20.1.

[0302] Embodiment 41

[0303]

[0304] Under nitrogen protection, 0.6mmol benzoic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12h, and the heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, wherein the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid with a volume ratio of 100:20:1, and the yield was 67%.

[0305] The structural characterization data of the obtained product are as follows:

[0306] 1 H NMR (400MHz, CDCl3) δ10.73(s,1H),8.08(s,1H),8.04(d,J=7.8Hz,1H),7.61(d,J=7.9Hz,1H),7.46(t,J=7.7Hz,1H ),3.81(t,J=7.8Hz,1H),3.69(s,3H),2.09-2.01(m,1H),1.79-1.62(m,6H),1.22-1.10(m,4H),0.99-0.89(m,2H).

[0307] 13 C NMR (101MHz, CDCl3) δ174.3,172.0,140.0,133.3,129.8,129.6,129.0,128.8,52.1,48.5,40.9,35.2,33.2,32.9,26.4,26.0,26.0.

[0308] Embodiment 42

[0309]

[0310] Under nitrogen protection, 0.6mmol benzoic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12h, and the heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, wherein the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid with a volume ratio of 60:20:1, and the yield was 79%.

[0311] The structural characterization data of the obtained product are as follows:

[0312] 1 H NMR (400MHz, CDCl3) δ10.28(s,1H),8.10-7.98(m,2H),7.60-7.53(m,1H),7.44(t,J=7.6Hz,1H),7.40-7.26(m,5H),5.15(d,J=35.1Hz, 2H),4.97(s,1H),3.72-3.58(m,4H),3.18(q,J=6.7Hz,2H),2.22-2.08(m,1H),1.90-1.76(m,1H),1.62-1.47(m,2H),1.36-1.23(m,2H).

[0313] 13 C NMR (101MHz, CDCl3) δ173.9,171.1,156.4,139.3,136.4,132.9,130.0,12 9.6,129.1,128.8,128.4,128.0,66.6,52.1,51.1,40.6,32.8,29.5,24.5.

[0314] Embodiment 43

[0315]

[0316] Under nitrogen protection, 0.6mmol benzoic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12h, and the heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, and the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid with a volume ratio of 80:20:1, and the yield was 61%.

[0317] The structural characterization data of the obtained product are as follows:

[0318] 1 H NMR (400MHz, CDCl3) δ10.42(s,1H),8.08-8.00(m,2H),7.58(d,J=7.8Hz,1H),7.46(t,J=7.8Hz,1H),3.75 (t,J=7.7Hz,1H),3.69(s,3H),3.67(s,3H),2.50-2.39(m,1H),2.31(t,J=7.2Hz,2H),2.23-2.10(m,1H).

[0319] 13 C NMR (101MHz, CDCl3) δ173.4,173.1,171.5,138.7,133.2,129.9,129.8,129.4,129.0,52.2,51.7,50.1,31.5,28.2.

[0320] Embodiment 44

[0321]

[0322] Under nitrogen protection, 0.6mmol benzoic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12h, and the heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, and the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid with a volume ratio of 140:20:1, and the yield was 79%.

[0323] The structural characterization data of the obtained product are as follows:

[0324] 1 H NMR (400MHz, CDCl3) δ10.64(s,1H),8.06(s,1H),8.01(d,J=7.7Hz,1H),7.56(d,J=7.7H z,1H),7.42(t,J=7.7Hz,1H),3.70(q,J=7.1Hz,1H),1.49(d,J=7.2Hz,3H),1.40(s,9H).

[0325] 13 C NMR (101MHz, CDCl3) δ173.4,172.2,141.6,132.8,129.7,129.4,128.8,128.6,80.9,46.3,27.9,18.3.

[0326] Embodiment 45

[0327]

[0328] Under nitrogen protection, 0.6mmol benzoic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12h, and the heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, and the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid with a volume ratio of 100:20:1, and the yield was 84%.

[0329] The structural characterization data of the obtained product are as follows:

[0330] 1 H NMR (400MHz, CDCl3) δ10.93(s,1H),8.19(s,1H),8.10(d,J=7.8Hz,1H),7.63(d,J=7.7Hz,1H),7.47(t,J=7.6Hz,1H),7.37-7.32(m,3H),7 .31-7.24(m,3H),7.22-7.16(m,4H),5.21-5.05(m,2H),4.09(t,J=7.9Hz,1H),3.54(dd,J=13.7,8.9Hz,1H),3.15(dd,J=13.8,6.8Hz,1H).

[0331] 13 C NMR (101MHz, CDCl3) δ172.7,138.9,138.3,135.5,133.4,129.8,129.3,128.9,128.8,128.4,128.4,128.1,127.9,126.5,66.7,53.3,39.6.

[0332] Embodiment 46

[0333]

[0334] Under nitrogen protection, 0.6mmol benzoic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12h, and the heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, wherein the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid in a volume ratio of 80:40:1, and the yield was 88%.

[0335] The structural characterization data of the obtained product are as follows:

[0336] 1 H NMR (400MHz, DMSO-d6) δ13.01(s,1H),9.20(s,1H),7.92(s,1H),7.85(d,J=7.7Hz,1H),7.55(d,J=6.3Hz,1H),7.43(t,J=7.7Hz,1H),6.96(d ,J=8.5Hz,2H),6.63(d,J=8.5Hz,2H),4.03(dd,J=8.5,7.2Hz,1H),3.53(s,3H),3.22(dd,J=13.8,8.6Hz,1H),2.91(dd,J=13.8,7.2Hz,1H).

[0337] 13 C NMR (101MHz, DMSO-d6) δ173.3,167.4,155.9,139.3,132.6,131.3,130.0,129.0,128.9,128.8,128.4,115.2,52.5,52.0,38.3.

[0338] Embodiment 47

[0339]

[0340] Under nitrogen protection, 0.6mmol benzoic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12h, and the heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, wherein the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid with a volume ratio of 80:40:1, and the yield was 81%.

[0341] The structural characterization data of the obtained product are as follows:

[0342] 1 H NMR (400MHz, CDCl3) δ11.13(s,1H),8.14(s,1H),8.08(d,J=7.8Hz,1H),7.62( d,J=7.8Hz,1H),7.51-7.44(m,3H),7.44-7.39(m,2H),7.39-7.33(m,1H),7.0 9(d,J=8.6Hz,2H),6.91(d,J=8.6Hz,2H),5.06(s,2H),3.98(dd,J=8.6,7.0Hz ,1H),3.68(s,3H),3.46(dd,J=13.9,8.6Hz,1H),3.08(dd,J=13.9,7.0Hz,1H).

[0343] 13 C NMR (101MHz, CDCl3) δ173.4,171.8,157.4,139.1,137.0,133.4,130.8,129.9,1 29.8,129.7,129.2,128.8,128.5,127.8,127.4,114.8,69.9,53.5,52.1,38.8.

[0344] Embodiment 48

[0345]

[0346] Under nitrogen protection, 0.6mmol benzoic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12h, and the heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, wherein the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid with a volume ratio of 60:20:1, and the yield was 54%.

[0347] The structural characterization data of the obtained product are as follows:

[0348] 1 H NMR (400MHz, CDCl3) δ9.54 (s, 1H), 8.10 (s, 1H), 8.05 (d, J = 7.8Hz, 1H), 7.82-7.74 (m, 3H),7.60-7.49(m,2H),7.44(t,J=7.7Hz,1H),7.24-7.15(m,2H),7.11(d,J=8.0Hz,2 H),6.91(dd,J=8.4,1.8Hz,2H),4.11(q,J=7.1Hz,1H),3.98-3.89(m,4H),3.64(s,3H ), 3.46(dd,J=13.9,8.7Hz,1H), 3.06(dd,J=13.8,6.8Hz,1H), 1.71(d,J=7.3Hz,3H).

[0349] 13 C NMR (101MHz, CDCl3) δ173.2,171.6,157.7,149.4,138.8,136.0,135.1,133.7,133.3,129.8,129.6,129 .3,129.3,128.9,128.8,127.3,126.1,126.0,121.3,119.0,105.6,55.2,53.2,52.1,45.5,38.9,18.4.

[0350] Embodiment 49

[0351]

[0352] Under nitrogen protection, 0.6mmol benzoic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction container in sequence, and the mixture was stirred at 80°C for 12h, and the heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, and the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid with a volume ratio of 80:20:1, and the yield was 65%.

[0353] The structural characterization data of the obtained product are as follows:

[0354] 1 H NMR (400MHz, CDCl3) δ10.13(s,1H),8.11(s,1H),8.06(d,J=7.7Hz,1H),7.57(d,J=7.7Hz,1H),7. 45(t,J=7.7Hz,1H),7.32(d,J=7.7Hz,2H),7.17(d,J=7.7Hz,2H),7.13(d,J=7.9Hz,2H),6.92(d, J=8.5Hz,2H),4.01-3.89(m,2H),3.64(s,3H),3.47(dd,J=13.9,8.7Hz,1H),3.07(dd,J=13.9,6. 8Hz, 1H), 2.50 (d, J = 7.1Hz, 2H), 1.96-1.83 (m, 1H), 1.62 (d, J = 7.1Hz, 3H), 0.94 (d, J = 6.6Hz, 6H).

[0355] 13 C NMR (101MHz, CDCl3) δ173.2,173.2,171.8,149.4,140.7,138.9,137.2,135.9,133.4,129.8 ,129.7,129.4,129.3,128.9,127.1,121.3,53.2,52.2,45.2,45.0,38.9,30.1,22.3,18.4.

[0356] Embodiment 50

[0357]

[0358] Under nitrogen protection, 0.6mmol benzoic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL 1,4-dioxane as solvent were added to the reaction vessel in sequence, and the reaction was stirred at 80°C for 12h, and the heating and stirring were stopped, and the reaction was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, and the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid with a volume ratio of 60:20:1, and the yield was 40%.

[0359] The structural characterization data of the obtained product are as follows:

[0360] 1 H NMR(400MHz, CDCl3)δ9.03(s,1H),8.01-7.92(m,2H),7.67-7.60(m,1H),7.42 (t,J=7.7Hz,1H),7.39-7.34(m,1H),7.32-7.20(m,3H),4.62(d,J=17.1Hz,1H ),4.37(d,J=17.1Hz,1H),3.81(dd,J=12.4,7.3Hz,1H),3.54-3.42(m,1H),2. 77(dd,J=13.5,6.6Hz,1H),2.69-2.57(m,1H),2.40-2.28(m,1H),1.43(s,9H).

[0361] 13 C NMR (101MHz, CDCl3) δ172.7,171.6,168.0,142.1,139.0,136.0,135.0,131.0,129 .4,129.2,128.9,128.1,127.8,126.7,122.2,81.9,51.1,47.1,37.6,29.8,28.0.

[0362] Embodiment 51

[0363]

[0364] Under nitrogen protection, 0.6 mmol benzoic acid, 0.3 mmol Katritzky salt substituted in the above reaction formula, 0.015 mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03 mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09 mmol lithium chloride, 0.6 mmol potassium acetate, 3 mL of a mixed solvent of tert-butanol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction vessel in sequence, and the mixture was stirred at 80°C for 12 h. The heating and stirring were stopped, and the mixture was cooled to room temperature. The solvent in the reaction solution was then distilled off under reduced pressure, and 1.5 mmol iodomethane and 0.6 mmol potassium carbonate were added, and the mixture was stirred at 60°C for 2 h. After the reaction is completed, the reaction solution is washed with a saturated sodium bicarbonate solution, extracted with ethyl acetate, the organic phases are combined, dried over anhydrous magnesium sulfate, filtered, the solvent is distilled off under reduced pressure, and separated and purified by column chromatography to obtain the target product, the column chromatography eluent used is a mixed solvent of petroleum ether:ethyl acetate in a volume ratio of 5:1, and the yield is 38%.

[0365] The structural characterization data of the obtained product are as follows:

[0366] 1 H NMR (400MHz, CDCl3) δ8.07(s,1H),7.96(d,J=7.8Hz,1H),7.67(d,J=7.8Hz,1H),7.54(s,1H),7.45-7.37(m,3H),7.3 0-7.13(m,7H),7.07(t,J=7.4Hz,1H),3.92-3.81(m,4H),3.63(dd,J=13.6,8.5Hz,1H),3.07(dd,J=13.6,6.4Hz,1H).

[0367] 13 C NMR (101MHz, CDCl3) δ170.5,167.0,139.8,139.0,137.6,132.4,130.4,129. 3,128.9,128.9,128.8,128.7,128.4,126.4,124.4,120.0,56.1,52.2,39.8.

[0368] Embodiment 52

[0369]

[0370] Under nitrogen protection, 0.6mmol 2,3-dimethylbenzoic acid, 0.3mmol Katritzky salt substituted in the above reaction formula, 0.015mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09mmol lithium chloride, 0.6mmol potassium acetate, 3mL mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction vessel in sequence, and the mixture was stirred at 80°C for 12 hours, and the heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and separated and purified by column chromatography to obtain the target product, and the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid with a volume ratio of 60:20:1, and the yield was 71%.

[0371] The structural characterization data of the obtained product are shown below:

[0372] 1 H NMR(500 MHz,DMSO-d6)δ12.86(s,1H),9.18(s,1H),7.55-7.48(m,1H),7.29(s,1H),7.02-6.96(m,2H),6.68-6.61 (m,2H),3.92-3.87(m,1H),3.51(s,3H),3.23-3.14(m,1H),2.91-2.83(m,1H),2.35(s,3H),2.25(s,3H).

[0373] 13 C NMR (126 MHz, DMSO-d6) δ173.4,169.8,155.9,138.1,135.7,135.6,132.4,132.1,129.9,129.1,126.7,115.2,52.2,51.9,38.1,20.3,16.2.

[0374] Embodiment 53

[0375]

[0376] Under nitrogen protection, 0.6 mmol 2,3-dimethylbenzoic acid, 0.3 mmol Katritzky salt substituted in the above reaction formula, 0.015 mmol dichloro(p-cymene)ruthenium(II) dimer, 0.03 mmol 5,5'-dimethyl-2,2'-bipyridine, 0.09 mmol lithium chloride, 0.6 mmol potassium acetate, 3 mL of a mixed solvent of tert-butyl alcohol and hexafluoroisopropanol (volume ratio of 9:1) were added to the reaction vessel in sequence, and the mixture was stirred at 80°C for 12 h, and the heating and stirring were stopped, and the mixture was cooled to room temperature. After the reaction was completed, the reaction solution was adjusted to pH=1 with 1M dilute hydrochloric acid, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, the solvent was removed by reduced pressure distillation, and the target product was separated and purified by column chromatography, and the column chromatography eluent used was a mixed solvent of petroleum ether: ethyl acetate: formic acid with a volume ratio of 60:20:1, and the yield was 48%.

[0377] The structural characterization data of the obtained product are as follows:

[0378] 1 H NMR (500 MHz, CDCl3) δ9.79 (s, 1H), 7.71 (s, 1H), 7.37-7.28 (m, 5H), 7.27-7.24 (m, 1H), 5.12 (d, J = 42.5 Hz,2H),4.90(s,1H),3.64(s,3H),3.51(t,J=7.7 Hz,1H),3.16(q,J=6.8Hz,2H),2.48(s,3H),2.31(s,3H),2.12-2.03(m,1H),1.81-1.72(m,1H),1.54-1.47(m,2H),1.30-1.22(m,2H).

[0379] 13 C NMR(126 MHz, CDCl3)δ174.2,173.2,156.4,138.6,137.6,136.5,135.8,133.1,130.1,12 8.4,128.1,128.0,127.9,66.6,52.0,50.7,40.7,32.7,29.5,24.6,20.6,16.5.

[0380] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be equivalent replacement methods and are included in the protection scope of the present invention.

Claims

1. A method for synthesizing a meta-secondary alkyl-substituted aryl carboxylic acid, characterized in that: The steps include: In a protective atmosphere, an organic solvent is used as a reaction medium, and an aryl carboxylic acid is reacted with a substituted Katritzky salt in the presence of a ruthenium catalyst, a ligand, an additive and a basic compound to obtain a meta-secondary alkyl-substituted aryl carboxylic acid; The structure of the aryl carboxylic acid is Dashed lines indicate looping or non-looping; When not forming a ring, R 1 , R 2 , R3 3 , R 4 each independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, halogen, -OH, substituted or unsubstituted alkoxy, aryl-O-, -NR'R", -NHC(=O)R', -NR'C(=O)R", -RC(=O)NHR', -C(=O)OR', -C(=O)R' or -OSO2R"', wherein R' and R" are H, C1-C6 alkyl, phenyl or benzyl, and R"' is C6-C 10 Aryl or substituted C6-C 10 Aryl; -NHC(=O)R' in which R' is not H, -NR'C(=O)R" in which R' and R" are not H, -C(=O)R' in which R' is not H; -RC(=O)NHR' in which R is an alkylene group and R' is not H; R 2 and R 4 At least one is H; When forming a ring, R 1 and R 2 Ring-forming and fused to a benzene ring or R 3 and R 4 The cyclic group obtained after the fusion is benzodioxanyl, methylenedioxybenzene ring, naphthalene ring, substituted naphthalene ring, benzofuran, benzotetrahydrofuran, benzo[b]thiophene, indolyl, substituted indolyl, substituted benzofuranyl; The structure of the Katritzky salt is R 5 Selected from C1-C 30 Alkyl, cycloalkyl, substituted alkyl, ester group; R 5 The substituted alkyl group refers to the alkyl group in which the hydrogen or carbon is replaced by a cycloalkyl group, CbzHN-, a phenyl group, or a substituted phenyl group; R 6 is one of -C(=O)OR' or -C(=O)NR'R", wherein R' is C1-C6 alkyl or benzyl; R" is H, C1-C6 alkyl, phenyl or benzyl; R 5 With R 6 Connected together into a ring, specifically X is selected from one of OTf, PF6 or BF4; The ruthenium catalyst is diiodo(p-cymene)ruthenium(II) dimer or dichloro(p-cymene)ruthenium(II) dimer; The ligand is selected from 2,2'-bipyridine, 5,5'-dimethyl-2,2'-bipyridine, 4,4'-di-tert-butyl-2,2'-bipyridine, 4,4'-dimethyl-2,2'-bipyridine, 4,4'-diphenyl-2,2'-bipyridine, 4,4'-dimethoxy-2,2'-bipyridine, 1,10-phenanthroline, 4,7-dimethoxy-1,10-phenanthroline, 3,4,7,8-tetramethyl-1,10-phenanthroline, 4,7-diphenyl-1,10-phenanthroline, 2-(5-tert-butyl-1H-3-pyrazolyl)pyridine, and one of triphenylphosphine; The additive is selected from lithium chloride and lithium trifluoromethanesulfonate.

2. The method for synthesizing the meta-secondary alkyl-substituted aryl carboxylic acid according to claim 1, characterized in that: When not forming a ring, R 1 , R 2 , R 3 , R 4 In the group selected from each of the following, the alkyl group is C1-C 20 Alkyl; the alkoxy group is C1-C 20 Alkoxy; the aryl group is C6-C 20 Aryl; The substituted alkyl refers to the hydrogen on the alkyl being replaced by a halogen; the substituted alkoxy refers to the hydrogen on the alkoxy being replaced by a halogen; the substituted aryl refers to the hydrogen on the aryl being replaced by an alkyl, halogen, ester, carbonyl, amine, amide, or hydroxyl group; The aryl in the aryl-O- is an aromatic hydrocarbon group, specifically phenyl or naphthyl; the substituted C6-C 10 Aryl is alkyl substituted C6-C 10 Aryl, halogen substituted C6-C 10 Aryl; -RC(=O)NHR', wherein R is a C1-C3 alkylene group; R 1 , R 2 , R 3 , R 4 2 of them are hydrogen, 3 of them are hydrogen, and 4 of them are hydrogen; When 3 are hydrogen atoms, R 1 Not hydrogen or R 3 Not hydrogen or R 4 Not hydrogen; When 2 are hydrogen atoms, R 2 and R 4 is hydrogen or R 1 and R 2 is hydrogen or R 2 and R 3 is hydrogen or R 3 and R 4 is hydrogen; The ligand is one of 2,2'-bipyridine, 5,5'-dimethyl-2,2'-bipyridine, 4,4'-di-tert-butyl-2,2'-bipyridine, 4,4'-dimethyl-2,2'-bipyridine and 4,4'-diphenyl-2,2'-bipyridine.

3. The method for synthesizing the meta-secondary alkyl-substituted aryl carboxylic acid according to claim 1, characterized in that: When forming a ring, R 3 and R 4 In the ring formation, the substituted naphthalene ring is a halogen-substituted naphthalene ring; the substituted indolyl refers to an alkyl-substituted indolyl, a halogen-substituted phenyl-substituted indolyl, specifically 1-alkylindolyl, 2-substituted phenylindolyl, 2-(halogen-substituted phenyl)1-alkylindolyl; the substituted benzofuranyl is 2-alkylbenzofuranyl, 2-(alkoxyphenyl)benzofuranyl; R 1 and R 2 The ring is formed and fused with a benzene ring, and the resulting ring is benzodioxole; R 5 The substituted phenyl is hydroxy substituted phenyl, benzyloxy substituted phenyl, 4. The method for synthesizing the meta-secondary alkyl-substituted aryl carboxylic acid according to claim 1, characterized in that: The alkaline compound is selected from one of potassium acetate, sodium acetate, cesium acetate, potassium carbonate, potassium phosphate, potassium pivalate, cesium pivalate, sodium pivalate, sodium carbonate, cesium carbonate, potassium tert-butoxide, and sodium tert-butoxide; The organic solvent is one of 1,4-dioxane, tert-butyl alcohol, and hexafluoroisopropanol, or a mixed solvent of the two solvents; The reaction temperature is 70 to 120° C. and the reaction time is 4 to 16 hours; The reaction molar ratio of the carboxylic acid to the Katritzky salt is (1.5-3):1; the molar ratio of the ruthenium catalyst to the Katritzky salt is (0.025-0.05):1; the molar ratio of the ligand to the Katritzky salt is (0.05-0.10):1, the molar ratio of the additive to the Katritzky salt is (0.10-1):1, and the molar ratio of the basic compound to the Katritzky salt is (1-3):1; After the reaction is completed, subsequent treatment is carried out.

5. The method for synthesizing the meta-secondary alkyl-substituted aryl carboxylic acid according to claim 4, characterized in that: The alkaline compound is selected from potassium acetate; The organic solvent is a mixed solvent of tert-butyl alcohol and hexafluoroisopropanol in a volume ratio of 4:1-20:1; After the reaction is completed, subsequent treatment is performed, wherein the subsequent treatment refers to cooling, adding dilute acid to a pH value of 0.5 to 1.5, extracting, removing the solvent in the organic phase, and separating and purifying; the extraction is ethyl acetate extraction; the separation is column chromatography separation; The eluent of the column chromatography is a mixed solvent of petroleum ether, ethyl acetate and formic acid, and the volume ratio of petroleum ether to ethyl acetate to formic acid is 120:20:1-80:40:

1.

6. The method for synthesizing the meta-secondary alkyl-substituted aryl carboxylic acid according to claim 1, characterized in that: Alternatively, after the reaction is completed, a methylation treatment is performed to improve the separation efficiency of the meta-position secondary alkyl-substituted aromatic carboxylic acid.

7. The method for synthesizing the meta-secondary alkyl-substituted aryl carboxylic acid according to claim 6, characterized in that: The methylation treatment refers to using N-methylpyrrolidone as a reaction medium to react the meta-position secondary alkylated aromatic carboxylic acid product with methyl iodide under the action of an alkaline compound; The subsequent treatment is performed after the methylation treatment, and the subsequent treatment at this time refers to quenching the reaction, ethyl acetate extraction, removal of the solvent in the organic phase, and column chromatography separation; Through methylation treatment, a meta-position secondary alkylated aromatic carboxylic acid methyl ester compound is obtained; The meta-position secondary alkylated aryl carboxylic acid methyl ester compound is treated by removing the methyl group to restore the carboxyl group.

8. The method for synthesizing the meta-secondary alkyl-substituted aryl carboxylic acid according to claim 7, characterized in that: In the methylation treatment, the reaction temperature is 55-65° C. and the reaction time is 2-3 hours. Before the methylation treatment, the reaction system, i.e., the product containing the meta-secondary alkylated aromatic carboxylic acid, is treated to remove the reaction solvent. The quenching reaction refers to adding a saturated sodium bicarbonate solution to the reaction system; the removal of the solvent in the organic phase refers to removing water in the organic phase and removing the organic solvent; the removal of water in the organic phase refers to drying with a desiccant, the desiccant is anhydrous magnesium sulfate, and then filtering; The eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is (3-20):

1.

9. The method for synthesizing the meta-secondary alkyl-substituted aryl carboxylic acid according to claim 6, characterized in that: Aryl carboxylic acids and Katritzky salts, When R 1 is alkyl, halogen, R 2 , R 3 , R 4 is hydrogen or R 3 is alkoxy, aryl-O-, -NHC(=O)R', -C(=O)OR', -C(=O)R' or -OSO2R"', halogen, R 1 , R 2 , R 4 is hydrogen; or R 1 is alkyl, halogen, R 4 is an alkyl group or an alkoxy group, R 2 , R 3 is hydrogen; or R 3 and R 4 The group fused to the benzene ring is a methylenedioxybenzene ring, a halogen-substituted naphthalene ring, benzo[b]thiophene, a substituted indolyl, or a 2-(alkoxyphenyl)benzofuranyl. 1 , R 2 is hydrogen; or R 1 and R 2 The ring is preferably benzodioxole, R 3 , R 4 When it is hydrogen, in order to improve the separation efficiency, methylation treatment is carried out after the reaction; The substituted indolyl refers to an alkyl-substituted indolyl, a halogen-substituted phenyl-substituted indolyl; or R 1 , R 2 , R 3 , R 4 is hydrogen, R 6 is one of -C(=O)O-Me or -C(=O)NH-Ph, R 5 In the case of isopropyl or benzyl, methylation treatment is performed after the reaction in order to improve the separation efficiency.

10. A meta-secondary alkyl-substituted aryl carboxylic acid obtained by the method according to any one of claims 1 to 9, characterized in that: R 2 When is hydrogen, the structure of the meta-secondary alkyl substituted aryl carboxylic acid is R 2 Not hydrogen, R 4 The structure of the hydrogen meta-position secondary alkyl substituted aromatic carboxylic acid is In the structural formula, R 1 ~R 5 As defined in claim 1.

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