Method for directly preparing carboxylic ester compound from aromatic aldehyde, ketone and carboxylic acid

Abstract

The invention provides a method for preparing carboxylic ester compounds with various structures and functions by carrying out direct reductive esterification on carbonyl compounds such as aromatic aldehyde and ketone and carboxylic acid under the action of diaryl phosphine oxide. The method is simple in condition and wide in substrate applicability, and can be compatible with various polar and reducing functional groups, such as alkyl hydroxyl, aromatic ketone carbonyl, primary and secondary amino, secondary amide and the like. Meanwhile, the reaction can also be well suitable for later-stage modification reaction of a series of carboxylic acid drugs with complex structures and amino acids, can also be directly used for efficient and high-selectivity synthesis of pyrethroid pesticides, and has potential application prospects and values in the fields of organic synthesis, medicines and pesticides.

Description

[Technical field]

[0001] The invention relates to the field of organic synthesis, and in particular to a method for directly preparing carboxylic acid ester compounds from aromatic aldehydes, ketones and carboxylic acids. [Background technology]

[0002] Carboxylic acid ester compounds are the basic structural units of natural products, drugs, pesticides, functional materials and fine chemicals. In nature, carboxylic acid ester compounds are the main source of the aroma of many flowers and fruits, and fats usually exist in the form of triesters. In industry, polyester materials, such as polyethylene terephthalate and cellulose acetate, are produced on a scale of over one million tons per year. In the pharmaceutical field, best-selling drugs such as Oseltamivir, Procaine, Methylphenidate and Fenofibrate all contain ester bonds. At the same time, carboxylic acid ester compounds are also widely used in the flavor and perfume industry as flavor additives.

[0003] Over the past century, chemists have developed many synthetic methods for the synthesis of carboxylic acid ester compounds. Among them, the dehydration condensation reaction between carboxylic acid and alcohol or phenol is the most common method, but such reactions require the use of strong acid conditions, resulting in a very limited range of functional groups. At the same time, alcohol or phenol substrates will inevitably undergo self-etherification side reactions, resulting in the need for a large excess of alcohol or phenol substrates or even acting as solvents, which lacks economy. Another common strategy for constructing carboxylic acid esters involves substitution reactions of halogen-containing reagents, including substitution reactions of alkyl halide reagents with carboxylic acids and substitution reactions of carboxylic acid derivatives such as acyl halides with alcohols or phenols. However, pre-synthesized active halogen-containing reagents are not only toxic, but also lack chemical selectivity, and their applicability in actual synthesis is severely limited. Therefore, the development of simple, green, general, and efficient carboxylic acid ester synthesis methods is an urgent need in the fields of chemistry, chemical engineering, and medicine.

[0004] In theory, it is an ideal strategy to synthesize carboxylate compounds by using carbonyl compounds such as aldehydes and ketones, which are widely available in nature, rich in variety, and diverse in structure and function, as raw materials and constructing C–O bonds with carboxylic acids through deoxygenation. However, only Chusov's group has reported two reactions in which aldehydes and carboxylic acids are reductively coupled to construct carboxylate esters under the catalysis of transition metal rhodium or ruthenium. The disadvantage is that both reactions are only applicable to specific acetic acid as the carboxylic acid substrate and lack universality. [References: (a) Welin, ER; Le, C.; Arias-Rotondo, DM; McCusker, JK; MacMillan, DWC Science 2017, 355, 380–385. (b) Science 2000,290,1140–1142.(c)AAi,H.-J.;Wang,H.;Li,C.-L.;Wu,X.-F.ACS Catal.2020,10,5147–5152.(d)Cheung,CW;Ploeger,ML;Hu,X.Nat.Commun.2017,8,14878.(e)Kitano,H.;Ito,H.;Itami,K.Palladium-Catalyzed Org.Lett.2018,20,2428–2432.(f)Liu,T.;Zhang,X.;Peng,Z.;Zhao,J.GreenChem.2021,23,9916–9921.(g)Zhang,Y.;Jian g, Y.; Wang, Y.; Sun, T.; Meng, Y.; Huang, Y.; Lv, X.; Gao, J.; Zhang, X.; Zhang, S.; Liu, S. Org. Lett.2022,24,2679–2683. (h) Fu rrow, ME; Myers, AGJ Am. Chem. Soc. 2004, 126, 12222–12223. (i) Ostrovskii, VS; Runikhina, SA; Afanasyev, OI; Chusov, D. Eur .J.Org.Chem.2020,2020,4116–4121.(j)Runikhina,SA;Usanov,DL;Chizhov,AO;Chusov,D.Org.Lett.2018,20,7856–7859.】

[0005] Based on this background, it is of great significance and research value to develop a simple, direct, efficient and universal method for the reductive esterification of carbonyl compounds such as aldehydes and ketones with carboxylic acids and to achieve the universal synthesis of a series of carboxylic acid ester compounds with diverse structures and functional groups. [Summary of the invention]

[0006] The purpose of the present invention is to develop a method for directly realizing reductive esterification of carbonyl compounds such as aromatic aldehydes and ketones with carboxylic acids under the action of diarylphosphine oxide, which can be used for the synthesis of carboxylic acid ester compounds with diverse structures and functions.

[0007] The objective of the present invention is achieved through the following technical solutions:

[0008] A method for directly preparing carboxylic acid ester compounds from aromatic aldehydes, ketones and carboxylic acids, wherein the synthetic raw materials of the carboxylic acid ester compounds include: aromatic aldehydes, ketone compounds, carboxylic acids, diarylphosphine oxides, bases and solvents;

[0009] The carboxylic acid ester compound has the following structural formula:

[0010]

[0011] In the structural formula, R 1 is a substituent at any one or more positions on the benzene ring, and R 1 R is independently selected from one of H, alkyl, alkoxy, aryl, halogen, and difluoromethoxy; 2 One selected from H or alkyl; R 3 One selected from an alkyl group or an aryl group.

[0012] Preferably, in the structural formula, R 1 is a substituent at any one or more positions on the benzene ring, and R 1 R is independently selected from one of H, methyl, tert-butyl, methoxy, phenyl, fluorine, chlorine, bromine, and difluoromethoxy; 2 One selected from H, methyl; R 3 One selected from butyl, cyclobutyl, adamantyl, benzyl, phenyl, 1-naphthyl, 2-naphthyl, pyrenyl, pyridyl, benzothienyl and quinolyl.

[0013] The aromatic aldehyde and ketone compound is selected from benzaldehyde, p-methylbenzaldehyde, p-tert-butylbenzaldehyde, p-fluorobenzaldehyde, p-chlorobenzaldehyde, p-bromobenzaldehyde, p-methoxybenzaldehyde, p-phenylbenzaldehyde, o-methylbenzaldehyde, m-chlorobenzaldehyde, 2-fluoro-4-methoxybenzaldehyde, 4-(methoxymethyl)benzaldehyde, 3-phenoxybenzaldehyde, 3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzaldehyde, and acetophenone.

[0014] The carboxylic acid is selected from the group consisting of n-pentanoic acid, 2-ethylbutyric acid, cyclobutylcarboxylic acid, adamantanecarboxylic acid, tiglic acid, 5-norbornene-2-carboxylic acid, 4-phenylbutyric acid, p-methoxyphenylacetic acid, p-chlorophenylacetic acid, p-bromophenylacetic acid, o-methylbenzoic acid, o-chlorobenzoic acid, p-fluorobenzoic acid, p-chlorobenzoic acid, p-bromobenzoic acid, p-phenoxybenzoic acid, p-dimethylaminobenzoic acid, p-methylmercaptobenzoic acid, p-trifluoromethoxybenzoic acid, p-trifluoromethylbenzoic acid, 4-[4-(2-(2-methyl-2-ol)-pyrrolidone] ... -(hydroxymethyl)benzoic acid, 4-methyl-1-naphthoic acid, 6-methoxy-2-naphthoic acid, 1-pyrenecarboxylic acid, 6-trifluoromethyl-pyridine-2-carboxylic acid, benzothiophene-3-carboxylic acid, quinoline-5-carboxylic acid, ibuprofen, naproxen, fenofibric acid, gemfibrozil, probenecid, mefenamic acid, flunilic acid, 2,2-dimethyl-3-(2-methylpropane-1-en-1-yl)cyclopropane-1-carboxylic acid, and one of flurbiprofen.

[0015] The diarylphosphine oxide is selected from one of diphenylphosphine oxide, bis(4-methylphenyl)phosphine oxide and bis(4-chlorophenyl)phosphine oxide.

[0016] The base is selected from one of cesium carbonate, potassium phosphate, sodium carbonate and potassium tert-butoxide.

[0017] Preferably, a method for directly preparing carboxylic acid ester compounds from aromatic aldehydes, ketones and carboxylic acids comprises the following steps: mixing aromatic aldehydes, ketone compounds, carboxylic acids, diarylphosphine oxides and bases; adding a solvent under an inert gas atmosphere, reacting to obtain a carboxylic acid ester product.

[0018] Further preferably, a method for directly preparing carboxylic acid ester compounds from aromatic aldehydes, ketones and carboxylic acids comprises the following steps: mixing aromatic aldehydes, ketone compounds, carboxylic acids, diaryl phosphine oxides and bases; adding a solvent under an inert gas atmosphere for stirring reaction, cooling to room temperature after the reaction is completed, washing with saturated ammonium chloride, extracting, drying, and removing the organic solvent by reduced pressure distillation. The crude product is separated by column chromatography to obtain a carboxylic acid ester product.

[0019] Further preferably, a method for directly preparing carboxylic acid ester compounds from aromatic aldehydes, ketones and carboxylic acids comprises the following steps: adding aromatic aldehydes, ketone compounds, carboxylic acids, diaryl phosphine oxides and bases to a reaction container in sequence and mixing; adding a solvent under an inert gas atmosphere, heating and stirring, cooling to room temperature after the reaction is completed, washing with saturated ammonium chloride, then extracting with dichloromethane, drying with anhydrous sodium sulfate, removing the organic solvent by reduced pressure distillation, and separating the crude product by column chromatography to obtain a carboxylic acid ester product.

[0020] The molar ratio of the aromatic aldehyde, the ketone compound, the carboxylic acid, the diarylphosphine oxide and the base is (1-3):1:(1-3):(1-5);

[0021] Preferably, the molar ratio of the aromatic aldehyde, the ketone compound, the carboxylic acid, the diarylphosphine oxide and the base is (1-2):1:(1-2):(1-3).

[0022] More preferably, the molar ratio of the aromatic aldehyde, the ketone compound, the carboxylic acid, the diarylphosphine oxide and the base is 1.2:1:1.2:2.

[0023] The solvent is one of N,N-dimethylformamide, dimethyl sulfoxide, acetonitrile, ethyl acetate and 1,4-dioxane.

[0024] The reaction temperature is 70-130°C; more preferably 120°C;

[0025] The reaction time is 8-24 hours, more preferably 12 hours.

[0026] The inert gas is nitrogen.

[0027] According to experimental research, the present invention provides a method for preparing a series of carboxylic acid ester compounds with diverse structures and functions by direct reduction esterification of carbonyl compounds such as aromatic aldehydes and ketones with carboxylic acids under the action of diarylphosphine oxide. The method has simple conditions and wide substrate applicability, and is compatible with a variety of polar and reducing functional groups, such as alkyl hydroxyl groups, aromatic ketone carbonyl groups, primary and secondary amino groups, secondary amide groups, etc. At the same time, the reaction can also be well applied to the late modification reactions of a series of complex carboxylic acid drugs and amino acids, and can also be directly used for the efficient and highly selective synthesis of pyrethroid pesticides, and has potential application prospects and value in the fields of organic synthesis, medicine and pesticides.

Brief Description of the Drawings

[0028] Figure 1 This is the reaction formula for preparing carboxylic acid ester compounds of the present invention. [Specific implementation method]

[0029] The synthesis method of the present invention is further described below in conjunction with the synthesis examples of the present invention. It should be noted that the examples do not limit the scope of protection claimed in the present invention.

[0030] This reaction may be achieved through the following ways:

[0031]

[0032] The nucleophilic substitution reaction of the above-mentioned benzyl diarylphosphonate intermediate with carboxylic acid has not been reported.

[0033] Synthesis example 1

[0034] Synthesis of Benzyl Valerate

[0035] 0.24mmol benzaldehyde, 0.2mmol n-pentanoic acid, 0.4mmol cesium carbonate, 0.24mmol bis(4-methylphenyl)phosphine oxide and 1ml N,N-dimethylformamide were added to the reaction vessel. The reaction was stirred at 120°C for 12h under nitrogen atmosphere, and the reaction was stopped, cooled to room temperature, washed with saturated ammonium chloride solution, and then extracted with dichloromethane, concentrated by vacuum distillation to remove the solvent, dried, and the crude product was separated by column chromatography to obtain the target product with a yield of 72%. 1 H NMR (400MHz, CDCl3) δ7.36 (s, 5H), 5.12 (s, 2H), 2.36 (d, J = 5.4Hz, 2H), 1.64 (s, 2H), 1.36 (d, J = 5.5Hz, 2H), 0.92 (s, 3H). 13 CNMR (101MHz, CDCl3) δ173.6,136.1,129.6,128.5,128.1,66.0,34.0,27.0,22.2,13.6.

[0036] Synthesis example 2

[0037] Synthesis of 1-Phenethyl N-Valerate

[0038] 0.24mmol acetophenone, 0.2mmol n-pentanoic acid, 0.4mmol cesium carbonate, 0.24mmol diphenylphosphine oxide and 1ml N,N-dimethylformamide were added to the reaction container. The reaction was stirred at 120°C for 12h under nitrogen atmosphere, and the reaction was stopped, cooled to room temperature, washed with saturated ammonium chloride solution, and then extracted with dichloromethane, concentrated by vacuum distillation to remove the solvent, dried, and the crude product was separated by column chromatography to obtain the target product with a yield of 62%. 1 H NMR (400MHz, CDCl3) δ7.35(d,J=4.3Hz,4H),7.30–7.26(m,1H),5.89(d,J=6.6Hz,1H),2.33(t,J=7.7Hz,2H ),1.61(dt,J=15.3,7.6Hz,2H),1.53(d,J=6.6Hz,3H),1.33(dq,J=14.7,7.3Hz,2H),0.90(t,J=7.4Hz,3H). 13 C NMR (101MHz, CDCl3) δ173.1,141.8,128.4,127.7,126.0,72.0,34.3,27.0,22.3,22.2,13.7.

[0039] Synthesis example 3

[0040] Synthesis of Benzyl Dodecanoate

[0041] 0.24mmol benzaldehyde, 0.2mmol lauric acid, 0.4mmol cesium carbonate, 0.24mmol diphenylphosphine oxide and 1ml N,N-dimethylformamide were added to the reaction container. The reaction was stirred at 120°C for 12h under nitrogen atmosphere, and the reaction was stopped, cooled to room temperature, washed with saturated ammonium chloride solution, and then extracted with dichloromethane, concentrated by vacuum distillation to remove the solvent, dried, and the crude product was separated by column chromatography to obtain the target product with a yield of 90%. 1 H NMR (400MHz, CDCl3) δ7.35 (s, 5H), 5.11 (s, 2H), 2.35 (t, J = 7.2Hz, 2H), 1.63 (d, J = 6.0Hz, 2H), 1.25 (s, 16H), 0.88 (t, J = 5.9Hz, 3H). 13 CNMR(101MHz, CDCl3)δ173.7,136.1,128.5,128.1,127.8,66.0,34.3,31.9,29.6,29.4,29.3,29.2,29.1,25.0,24.7,22.7,14.1.

[0042] Synthesis example 4

[0043] Synthesis of 4-Methylbenzyl 2-ethylbutyrate

[0044] 0.24mmol p-methylbenzaldehyde, 0.2mmol 2-ethylbutyric acid, 0.4mmol cesium carbonate, 0.24mmol diphenylphosphine oxide and 1ml N,N-dimethylformamide were added to the reaction container. The reaction was stirred at 120°C for 12h under nitrogen atmosphere, and the reaction was stopped, cooled to room temperature, washed with saturated ammonium chloride solution, and then extracted with dichloromethane, concentrated by vacuum distillation to remove the solvent, dried, and the crude product was separated by column chromatography to obtain the target product with a yield of 85%. 1 H NMR (400MHz, CDCl3) δ7.28(d,J=7.1Hz,2H),7.20(d,J=7.5Hz,2H),5.13(s,2H),2.38(s,3H),2.3 3–2.24(m,1H),1.68(tt,J=15.3,7.6Hz,2H),1.56(tt,J=13.2,6.7Hz,2H),0.92(t,J=7.3Hz,6H). 13 C NMR (101MHz, CDCl3) δ176.1,137.8,133.3,129.1,128.2,65.8,48.9,25.0,21.1,11.8.

[0045] Synthesis example 5

[0046] Synthesis of 4-methoxybenzyl 2,2,3,3-tetramethylcyclopropane-1-carboxylate

[0047] 0.24mmol p-methoxybenzaldehyde, 0.2mmol 2,2,3,3-tetramethylcyclopropane-1-carboxylic acid, 0.4mmol cesium carbonate, 0.24mmol diphenylphosphine oxide and 1ml N,N-dimethylformamide were added to the reaction container. The reaction was stirred at 120°C for 12h under nitrogen atmosphere, and the reaction was stopped, cooled to room temperature, washed with saturated ammonium chloride solution, and then extracted with dichloromethane, concentrated by vacuum distillation to remove the solvent, dried, and the crude product was separated by column chromatography to obtain the target product with a yield of 96%. 1 H NMR (400MHz, CDCl3) δ7.30 (d, J = 7.7Hz, 2H), 6.89 (d, J = 7.6Hz, 2H), 5.02 (s, 2H), 3.80 (s, 3H), 1.26 (s, 6H), 1.23 (s, 1H), 1.18 (s, 6H). 13 C NMR (101MHz, CDCl3) δ171.9,159.4,129.9,128.6,113.8,65.2,55.2,35.7,30.0,23.4,16.5.

[0048] Synthesis example 6

[0049] Synthesis of 4-(tert-butyl)benzylcyclobutanecarboxylate

[0050] 0.24mmol of p-tert-butylbenzaldehyde, 0.2mmol of cyclobutylcarboxylic acid, 0.4mmol of cesium carbonate, 0.24mmol of diphenylphosphine oxide and 1ml of N,N-dimethylformamide were added to the reaction vessel. The reaction was stirred at 120°C for 12h under nitrogen atmosphere, and the reaction was stopped, cooled to room temperature, washed with saturated ammonium chloride solution, and then extracted with dichloromethane, concentrated by vacuum distillation to remove the solvent, dried, and the crude product was separated by column chromatography to obtain the target product with a yield of 95%. 1 H NMR (400MHz, CDCl3) δ7.42(d,J=7.2Hz,2H),7.32(d,J=7.3Hz,2H),5.12(s,2H),3.31– 3.05(m,1H),2.42–2.29(m,2H),2.23(d,J=7.9Hz,2H),2.08–1.85(m,2H),1.35(s,9H). 13 C NMR (101MHz, CDCl3) δ175.4,151.2,133.2,127.9,125.5,65.9,38.1,34.6,31.3,25.3,18.4.

[0051] Synthesis Example 7

[0052] Synthesis of [1,1'-biphenyl]-4-yl-methyl (1s,3s)-adamantane-1-carboxylate

[0053] 0.24mmol p-phenylbenzaldehyde, 0.2mmol adamantanecarboxylic acid, 0.4mmol cesium carbonate, 0.24mmol diphenylphosphine oxide and 1ml N,N-dimethylformamide were added to the reaction container. The reaction was stirred at 120°C for 12h under nitrogen atmosphere, and the reaction was stopped, cooled to room temperature, washed with saturated ammonium chloride solution, and then extracted with dichloromethane, concentrated by vacuum distillation to remove the solvent, dried, and the crude product was separated by column chromatography to obtain the target product with a yield of 90%. 1 H NMR (400MHz, CDCl3) δ7.59 (d, J=7.6Hz, 4H), 7.43 (dd, J=16.6, 7.5Hz, 4H), 7.38 –7.31(m,1H),5.14(s,2H),2.03(s,3H),1.95(s,6H),1.72(s,5H),1.58(s,1H). 13 C NMR (101MHz, CDCl3) δ177.5,140.9,140.7,135.6,128.8,128.1,127.4,127.2,127.1,65.5,40.8,38.9,36.5,28.0.

[0054] Synthesis example 8

[0055] Synthesis of 2-Methylbenzyl (E)-2-methylbutane-2-enoate

[0056] 0.24mmol o-methylbenzaldehyde, 0.2mmol tiglic acid, 0.4mmol cesium carbonate, 0.24mmol diphenylphosphine oxide and 1ml N,N-dimethylformamide were added to the reaction vessel. The reaction was stirred at 120°C for 12h under nitrogen atmosphere, and the reaction was stopped, cooled to room temperature, washed with saturated ammonium chloride solution, and then extracted with dichloromethane, concentrated by vacuum distillation to remove the solvent, dried, and the crude product was separated by column chromatography to obtain the target product with a yield of 83%. 1 HNMR (400MHz, CDCl3) δ7.38(d,J=6.7Hz,1H),7.31–7.18(m,3H),6.94(q,J=6.5Hz,1H),5.23(s,2H),2.40(s,3H),1.90(s,3H),1.82(d,J=6.9Hz,3H). 13C NMR (101MHz, CDCl3) δ167.8,137.4,136.8,134.3,130.2,128.9,128.5,128.3,125.9,64.6,18.9,14.3,12.0.

[0057] Synthesis example 9

[0058] Synthesis of 4-Methylbenzyl 2-(4-methoxyphenyl)acetate

[0059] 0.24mmol p-tolualdehyde, 0.2mmol p-methoxyphenylacetic acid, 0.4mmol cesium carbonate, 0.24mmol diphenylphosphine oxide and 1ml N,N-dimethylformamide were added to the reaction vessel. The reaction was stirred at 120°C for 12h under nitrogen atmosphere, and the reaction was stopped, cooled to room temperature, washed with saturated ammonium chloride solution, and then extracted with dichloromethane, concentrated by vacuum distillation to remove the solvent, dried, and the crude product was separated by column chromatography to obtain the target product with a yield of 81%. 1 HNMR (400MHz, CDCl3) δ7.30–7.18(m,6H),6.90(d,J=7.6Hz,2H),5.13(s,2H),3.83(s,3H),3.63(s,2H),2.39(s,3H). 13 C NMR (101MHz, CDCl3) δ171.7,158.7,138.0,132.9,130.3,129.2,128.3,126.0,114.0,66.5,55.2,40.4,21.1.

[0060] Synthesis example 10

[0061] Synthesis of 4-Methylbenzyl 2-(4-chlorophenyl)acetate

[0062] 0.24mmol p-tolualdehyde, 0.2mmol p-chlorophenylacetic acid, 0.4mmol cesium carbonate, 0.24mmol diphenylphosphine oxide and 1ml N,N-dimethylformamide were added to the reaction container. The reaction was stirred at 120°C for 12h under nitrogen atmosphere, and the reaction was stopped, cooled to room temperature, washed with saturated ammonium chloride solution, and then extracted with dichloromethane, concentrated by vacuum distillation to remove the solvent, dried, and the crude product was separated by column chromatography to obtain the target product with a yield of 68%. 1 HNMR (400MHz, CDCl3) δ7.33(d,J=7.5Hz,2H),7.25(d,J=6.8Hz,4H),7.20(d,J=7.5Hz,2H),5.13(s,2H),3.66(s,2H),2.39(s,3H). 13C NMR (101MHz, CDCl3) δ170.9,138.1,133.0,132.6,132.3,130.6,129.2,128.6,128.3,66.7,40.6,21.1.

[0063] Synthesis Example 11

[0064] Synthesis of Quinolin-8-yl-Methyl 4-phenylbutyrate

[0065] 0.24mmol 8-quinolinecarboxylic acid, 0.2mmol 4-phenylbutyric acid, 0.4mmol cesium carbonate, 0.24mmol diphenylphosphine oxide and 1ml N,N-dimethylformamide were added to the reaction container. The reaction was stirred at 120°C for 12h under nitrogen atmosphere, and the reaction was stopped, cooled to room temperature, washed with saturated ammonium chloride solution, and then extracted with dichloromethane, concentrated by vacuum distillation to remove the solvent, dried, and the crude product was separated by column chromatography to obtain the target product with a yield of 86%. 1 H NMR (400MHz, CDCl3) δ9.02–8.93(m,1H),8.18(d,J=8.2Hz,1H),7.87–7.73(m,2H),7.56(t,J=7.6Hz,1H),7.45(dd,J=7.8,4.0Hz,1H ),7.29(t,J=7.1Hz,2H),7.20(dd,J=14.6,7.2Hz,3H),5.91(s,2H),2.69(t,J=7.5Hz,2H),2.47(t,J=7.4Hz,2H),2.15–2.01(m,2H). 13 C NMR (101MHz, CDCl3) δ173.3,149.8,146.1,141.4,136.1,134.3,128.6,128.4,128.3,128.1,128.0,126.1,125.8,121.2,62.6,35.1,33.7,26.5.

[0066] Synthesis example 12

[0067] Synthesis of 4-Methylbenzyl 2-methylbenzoate

[0068] 0.24mmol p-tolualdehyde, 0.2mmol o-toluic acid, 0.4mmol cesium carbonate, 0.24mmol diphenylphosphine oxide and 1ml N,N-dimethylformamide were added to the reaction vessel. The reaction was stirred at 120°C for 12h under nitrogen atmosphere, and the reaction was stopped, cooled to room temperature, washed with saturated ammonium chloride solution, and then extracted with dichloromethane, concentrated by vacuum distillation to remove the solvent, dried, and the crude product was separated by column chromatography to obtain the target product with a yield of 94%. 1 H NMR (400MHz, CDCl3) δ8.00(d,J=7.7Hz,1H),7.42(dd,J=17.0,7.7Hz,3H),7.26(dd,J=14.1,7.4Hz,4H),5.36(s,2H),2.66(s,3H),2.41(s,3H). 13 C NMR (101MHz, CDCl3) δ167.4,140.2,138.0,133.1,131.9,131.6,130.6,129.6,129.2,128.3,125.6,66.4,21.7,21.2.

[0069] Synthesis example 13

[0070] Synthesis of 4-Methylbenzyl 4-fluorobenzoate

[0071] 0.24mmol p-tolualdehyde, 0.2mmol p-fluorobenzoic acid, 0.4mmol cesium carbonate, 0.24mmol diphenylphosphine oxide and 1ml N,N-dimethylformamide were added to the reaction vessel. The reaction was stirred at 120°C for 12h under nitrogen atmosphere, and the reaction was stopped, cooled to room temperature, washed with saturated ammonium chloride solution, and then extracted with dichloromethane, concentrated by vacuum distillation to remove the solvent, dried, and the crude product was separated by column chromatography to obtain the target product with a yield of 72%. 1 H NMR (400MHz, CDCl3) δ8.15–8.03(m,2H),7.35(d,J=7.4Hz,2H),7.21(d,J=7.5Hz,2H),7.10(t,J=8.1Hz,2H),5.33(s,2H),2.38(s,3H). 13 C NMR (101MHz, CDCl3) δ167.0, 165.0 (d, J = 97.6Hz), 138.1, 132.9, 132.2 (d, J = 9.3Hz), 129.3, 128.4, 126.5 (d, J = 2.9Hz), 115.4 (d, J = 22.0Hz). 19 FNMR (377MHz,CDCl3)δ-105.62.

[0072] Synthesis example 14

[0073] Synthesis of 4-Methylbenzyl 4-chlorobenzoate

[0074] 0.24mmol p-tolualdehyde, 0.2mmol p-chlorobenzoic acid, 0.4mmol cesium carbonate, 0.24mmol diphenylphosphine oxide and 1ml N,N-dimethylformamide were added to the reaction vessel. The reaction was stirred at 120°C for 12h under nitrogen atmosphere, and the reaction was stopped, cooled to room temperature, washed with saturated ammonium chloride solution, and then extracted with dichloromethane, concentrated by vacuum distillation to remove the solvent, dried, and the crude product was separated by column chromatography to obtain the target product with a yield of 74%. 1 H NMR (400MHz, CDCl3) δ8.00(d,J=7.9Hz,2H),7.40(d,J=8.0Hz,2H),7.34(d,J=7.4Hz,2H),7.21(d,J=7.5Hz,2H),5.33(s,2H),2.37(s,3H). 13 C NMR (101MHz, CDCl3) δ165.5,139.4,138.2,132.7,131.0,129.3,128.6,128.5,128.4,66.9,21.2.

[0075] Synthesis Example 15

[0076] Synthesis of 4-Methylbenzyl 4-Methylmercaptobenzoate

[0077] 0.24mmol p-methylbenzaldehyde, 0.2mmol p-methylmercaptobenzoic acid, 0.4mmol cesium carbonate, 0.24mmol diphenylphosphine oxide and 1ml N,N-dimethylformamide were added to the reaction container. The reaction was stirred at 120°C for 12h under nitrogen atmosphere, and the reaction was stopped, cooled to room temperature, washed with saturated ammonium chloride solution, and then extracted with dichloromethane, concentrated by vacuum distillation to remove the solvent, dried, and the crude product was separated by column chromatography to obtain the target product with a yield of 89%. 1 H NMR (400MHz, CDCl3) δ8.00(d,J=7.6Hz,2H),7.37(d,J=7.1Hz,2H),7.25(dd,J=15.3,7.8Hz,4H),5.35(s,2H),2.53(s,3H),2.40(s,3H). 13 C NMR (101MHz, CDCl3) δ166.1,145.5,138.0,133.1,129.9,129.2,128.2,126.3,124.9,66.5,21.1,14.7.

[0078] Synthesis Example 16

[0079] Synthesis of 4-Methylbenzyl 4-trifluoromethylbenzoate

[0080] 0.24mmol p-tolualdehyde, 0.2mmol p-trifluoromethylbenzoic acid, 0.4mmol cesium carbonate, 0.24mmol diphenylphosphine oxide and 1ml N,N-dimethylformamide were added to the reaction vessel. The reaction was stirred at 120°C for 12h under nitrogen atmosphere, and the reaction was stopped, cooled to room temperature, washed with saturated ammonium chloride solution, and then extracted with dichloromethane, concentrated by vacuum distillation to remove the solvent, dried, and the crude product was separated by column chromatography to obtain the target product with a yield of 78%. 1 H NMR (400MHz, CDCl3) δ8.18(d,J=7.8Hz,2H),8.01–7.62(m,2H),7.36(d,J=7.3Hz,2H),7.23(t,J=9.4Hz,2H),5.36(s,2H),2.38(s,3H). 13 C NMR (101MHz, CDCl3) δ165.2, 138.3, 134.4 (q, J = 32.6Hz), 133.5, 132.6, 130.0, 129.3, 128.5, 125.3 (q, J = 3.7Hz), 122.3, 67.2, 21.2. 19 FNMR (376MHz, CDCl3)δ-63.12.

[0081] Synthesis Example 17

[0082] Synthesis of 4-bromobenzyl 4-methyl-1-naphthoate

[0083] 0.24mmol of p-bromobenzaldehyde, 0.2mmol of 4-methyl-1-naphthoic acid, 0.4mmol of cesium carbonate, 0.24mmol of diphenylphosphine oxide and 1ml of N,N-dimethylformamide were added to the reaction vessel. The reaction was stirred at 120°C for 12h under a nitrogen atmosphere, and the reaction was stopped, cooled to room temperature, washed with saturated ammonium chloride solution, and then extracted with dichloromethane, concentrated by vacuum distillation to remove the solvent, and dried. The crude product was separated by column chromatography to obtain the target product with a yield of 90%. 1 H NMR (400MHz, CDCl3) δ9.05(d,J=8.5Hz,1H),8.14(d,J=7.4Hz,1H),8.05(d,J=8.3Hz,1H),7.6 7–7.57(m,2H),7.53(d,J=7.9Hz,2H),7.35(dd,J=14.9,7.7Hz,3H),5.39(s,2H),2.74(s,3H).13 CNMR(101MHz, CDCl3)δ167.0,140.6,135.2,132.8,131.7,131.4,130.2,129.8,127.4,126.2,126.0,125.4,124.8,124.4,122.1,65.7,20.0.

[0084] Synthesis example 18

[0085] Synthesis of 4-Chlorobenzyl 6-methoxy-2-naphthoate

[0086] 0.24mmol p-chlorobenzaldehyde, 0.2mmol 6-methoxy-2-naphthoic acid, 0.4mmol cesium carbonate, 0.24mmol diphenylphosphine oxide and 1ml N,N-dimethylformamide were added to the reaction vessel. The reaction was stirred at 120°C for 12h under nitrogen atmosphere, and the reaction was stopped, cooled to room temperature, washed with saturated ammonium chloride solution, and then extracted with dichloromethane, concentrated by vacuum distillation to remove the solvent, dried, and the crude product was separated by column chromatography to obtain the target product with a yield of 74%. 1 HNMR (400MHz, CDCl3) δ8.54(s,1H),8.05(d,J=8.5Hz,1H),7.82(d,J=8.9Hz,1H),7.74(d,J=8.5Hz ,1H),7.39(dd,J=19.2,7.9Hz,4H),7.19(d,J=8.9Hz,1H),7.13(s,1H),5.36(s,2H),3.92(s,3H). 13 C NMR (101MHz, CDCl3) δ166.5,159.6,137.2,134.7,134.0,130.9,130.8,129.5,128.7,127.8126.8,125.8,124.8,119.6,105.6,65.7,55.3.

[0087] Synthesis example 19

[0088] Synthesis of Benzylpyrene-1-carboxylate

[0089] 0.24mmol benzaldehyde, 0.2mmol 1-pyrenecarboxylic acid, 0.4mmol cesium carbonate, 0.24mmol diphenylphosphine oxide and 1ml N,N-dimethylformamide were added to the reaction vessel. The reaction was stirred at 120°C for 12h under nitrogen atmosphere, and the reaction was stopped, cooled to room temperature, washed with saturated ammonium chloride solution, and then extracted with dichloromethane, concentrated by vacuum distillation to remove the solvent, dried, and the crude product was separated by column chromatography to obtain the target product with a yield of 75%. 1HNMR (400MHz, CDCl3) δ9.30(d,J=9.4Hz,1H),8.65(d,J=8.1Hz,1H),8.20(t,J=8.9Hz,3H),8.09(t,J=8.5Hz,2 H),8.01(dd,J=11.9,7.4Hz,2H),7.60(d,J=7.4Hz,2H),7.47(t,J=7.3Hz,2H),7.44–7.36(m,1H),5.58(s,2H). 13 C NMR (101MHz, CDCl3) δ167.6,136.2,134.3,131.2,130.9,130.2,129.5,129.4,128.6,12 8.4,128.3,128.2,127.0,126.3,126.2,126.1,124.8,124.7,124.0,124.0,123.1,66.9.

[0090] Synthesis example 20

[0091] Synthesis of 3-Chlorobenzyl 6-(trifluoromethyl)picolinate

[0092] 0.24mmol m-chlorobenzaldehyde, 0.2mmol 6-trifluoromethyl-pyridine-2-carboxylic acid, 0.4mmol cesium carbonate, 0.24mmol diphenylphosphine oxide and 1ml N,N-dimethylformamide were added to the reaction vessel. The reaction was stirred at 120°C for 12h under nitrogen atmosphere, and the reaction was stopped, cooled to room temperature, washed with saturated ammonium chloride solution, and then extracted with dichloromethane, concentrated by vacuum distillation to remove the solvent, dried, and the crude product was separated by column chromatography to obtain the target product with a yield of 61%. 1 H NMR (400MHz, CDCl3) δ8.28 (d, J = 7.7Hz, 1H), 8.04 (t, J = 7.7Hz, 1H), 7.86 (d, J = 7.7Hz, 1H), 7.46 (s, 1H), 7.32 (d, J = 14.4Hz, 3H), 5.42 (s, 2H). 13 C NMR(101MHz,CDCl3)δ163.7,148.6(q,J=35.6Hz),148.3,138.8,137.3,134.5,12 9.9,128.6,128.4,127.6,126.4,123.6(d,J=2.5Hz),121.0(d,J=274.7Hz),66.8. 19 FNMR (376MHz,CDCl3)δ-67.7.

[0093] Synthesis Example 21

[0094] Synthesis of 4-Fluorobenzylbenzo[b]thiophene-3-carboxylate

[0095] 0.24mmol p-fluorobenzaldehyde, 0.2mmol 3-benzothiophenecarboxylic acid, 0.4mmol cesium carbonate, 0.24mmol diphenylphosphine oxide and 1ml N,N-dimethylformamide were added to the reaction vessel. The reaction was stirred at 120°C for 12h under nitrogen atmosphere, and the reaction was stopped, cooled to room temperature, washed with saturated ammonium chloride solution, and then extracted with dichloromethane, concentrated by vacuum distillation to remove the solvent, dried, and the crude product was separated by column chromatography to obtain the target product with a yield of 85%. 1 HNMR (400MHz, CDCl3) δ8.61(d,J=8.1Hz,1H),8.40(s,1H),7.86(d,J=7.9Hz,1H),7.55–7.37(m,4H),7.09(t,J=7.9Hz,2H),5.37(s,2H). 13 C NMR (101MHz, CDCl3) δ163.1(d,J=152.2Hz),161.4,139.9,136.9,136.6,131.9(d,J=3.2 Hz), 130.20 (d, J = 8.3Hz), 126.8, 125.4, 125.0, 124.6, 122.4, 115.5 (d, J = 21.6Hz), 65.6. 19 F NMR (376MHz,CDCl3)δ-113.43.

[0096] Synthesis example 22

[0097] Synthesis of 4-Fluorobenzyl 2-(4-isobutylphenyl)propionate

[0098] 0.24mmol p-fluorobenzaldehyde, 0.2mmol ibuprofen, 0.4mmol cesium carbonate, 0.24mmol diphenylphosphine oxide and 1ml N,N-dimethylformamide were added to the reaction vessel. The reaction was stirred at 120°C for 12h under nitrogen atmosphere, and the reaction was stopped, cooled to room temperature, washed with saturated ammonium chloride solution, and then extracted with dichloromethane, concentrated by vacuum distillation to remove the solvent, dried, and the crude product was separated by column chromatography to obtain the target product with a yield of 73%. 1H NMR (400MHz, CDCl3) δ7.18(d,J=6.6Hz,4H),7.09(d,J=7.2Hz,2H),6.97(t,J=8.0Hz,2H),5.07(s,2H),3.7 4(d,J=7.0Hz,1H),2.46(d,J=6.9Hz,2H),1.96–1.75(m,1H),1.50(d,J=6.9Hz,3H),0.91(d,J=6.2Hz,6H). 13 C NMR (101MHz, CDCl3) δ174.4,162.5(d,J=246.5Hz),140.6,137.5,131.9(d,J=3.3Hz),12 9.7(d,J=8.2Hz),129.3,127.2,115.3(d,J=21.6Hz),65.5,45.1,45.0,30.2,22.3,18.3. 19 F NMR (377MHz,CDCl3)δ-114.00.

[0099] Synthesis example 23

[0100] Synthesis of Benzyl 2-(6-Methoxynaphthalen-2-yl) Propionate

[0101] 0.24mmol benzaldehyde, 0.2mmol naproxen, 0.4mmol cesium carbonate, 0.24mmol diphenylphosphine oxide and 1ml N,N-dimethylformamide were added to the reaction container. The reaction was stirred at 120°C for 12h under nitrogen atmosphere, and the reaction was stopped, cooled to room temperature, washed with saturated ammonium chloride solution, and then extracted with dichloromethane, concentrated by vacuum distillation to remove the solvent, dried, and the crude product was separated by column chromatography to obtain the target product with a yield of 85%. 1 H NMR(400MHz, CDCl3)δ7.77–7.67(m,3H),7.46(d,J=8.4Hz,1H),7.35–7.24(m,5H),7.22–7 .12(m,2H),5.17(q,J=12.5Hz,2H),3.99–3.94(m,1H),3.93(s,3H),1.65(d,J=7.1Hz,3H). 13 C NMR (101MHz, CDCl3) δ174.3,157.6,135.9,135.5,133.6,129.2,128.9,128. 4,128.0,127.8,127.1,126.2,125.9,118.9,105.5,66.4,55.2,45.4,18.5.

[0102] Synthesis example 24

[0103] Synthesis of 4-methylbenzyl 2-(3-(4-chlorobenzoyl)phenoxy)-2-methylpropionate

[0104] 0.24mmol p-tolualdehyde, 0.2mmol fenofibric acid, 0.4mmol cesium carbonate, 0.24mmol diphenylphosphine oxide and 1ml N,N-dimethylformamide were added to the reaction vessel. The reaction was stirred at 120°C for 12h under nitrogen atmosphere, and the reaction was stopped, cooled to room temperature, washed with saturated ammonium chloride solution, and then extracted with dichloromethane, concentrated by vacuum distillation to remove the solvent, dried, and the crude product was separated by column chromatography to obtain the target product with a yield of 65%. 1 H NMR (400MHz, CDCl3) δ7.71–7.66(m,2H),7.66–7.61(m,2H),7.49–7.36(m,2H),7.14(d,J=8 .1Hz,2H),7.09(d,J=8.0Hz,2H),6.84–6.66(m,2H),5.16(s,2H),2.29(s,3H),1.67(s,6H). 13 C NMR (101MHz, CDCl3) δ194.0,173.3,159.4,138.2,138.1,136.3,132.0,131.8,131.0,130.1,129.1,128.5,128.4,117.1,79.3,67.2,25.3,21.0.

[0105] Synthesis example 25

[0106] Synthesis of 3-Chlorobenzyl 5-(2,5-dimethylphenoxy)-2,2-dimethylvalerate

[0107] Add 0.24mmol m-chlorobenzaldehyde, 0.2mmol gemfibrozil, 0.4mmol cesium carbonate, 0.24mmol diphenylphosphine oxide and 1ml N,N-dimethylformamide into the reaction vessel. Stir the reaction at 120℃ for 12h under nitrogen atmosphere, stop the reaction, cool to room temperature, wash with saturated ammonium chloride solution, extract with dichloromethane, concentrate under reduced pressure to remove the solvent, dry, and separate the crude product by column chromatography to obtain the target product with a yield of 71%. 1H NMR (400MHz, CDCl3) δ7.35(s,1H),7.29(d,J=4.0Hz,2H),7.24(s,1H),7.01(d,J=7.4Hz,1H),6.68(d,J=7.4H z,1H),6.62(s,1H),5.09(s,2H),3.92(d,J=5.6Hz,2H),2.32(s,3H),2.18(s,3H),1.76(s,4H),1.28(s,6H). 13 C NMR (101MHz, CDCl3) δ177.3,156.9,138.3,136.3,134.3,130.2,129.7,128.1,1 27.8,125.8,123.5,120.7,111.9,67.8,65.2,42.1,37.1,25.1,25.0,21.315.7.

[0108] Synthesis Example 26

[0109] Synthesis of 4-Methylbenzyl 4-(N,N-diisopropylsulfamoyl)benzoate

[0110] 0.24mmol p-tolualdehyde, 0.2mmol probenecid, 0.4mmol cesium carbonate, 0.24mmol diphenylphosphine oxide and 1ml N,N-dimethylformamide were added to the reaction container. The reaction was stirred at 120°C for 12h under nitrogen atmosphere, and the reaction was stopped, cooled to room temperature, washed with saturated ammonium chloride solution, and then extracted with dichloromethane, concentrated by vacuum distillation to remove the solvent, dried, and the crude product was separated by column chromatography to obtain the target product with a yield of 93%. 1 H NMR (400MHz, CDCl3) δ8.16(d,J=7.9Hz,2H),7.85(d,J=7.9Hz,2H),7.34(d,J=7.4Hz,2H),7.19(d,J=7 .5Hz,2H),5.34(s,2H),3.09(t,J=7.5Hz,4H),2.35(s,3H),1.68–1.40(m,4H),0.86(t,J=7.3Hz,6H). 13 CNMR (101MHz, CDCl3) δ164.9,144.2,138.2,133.4,132.4,130.2,129.2,128.4,126.8,67.1,49.8,21.8,21.1,11.0.

[0111] Synthesis Example 27

[0112] Synthesis of 4-methylbenzyl 2-((2,3-dimethylphenyl)amino)benzoate

[0113] 0.24mmol p-tolualdehyde, 0.2mmol formic acid, 0.4mmol cesium carbonate, 0.24mmol diphenylphosphine oxide and 1ml N,N-dimethylformamide were added to the reaction container. The reaction was stirred at 120°C for 12h under nitrogen atmosphere, and the reaction was stopped, cooled to room temperature, washed with saturated ammonium chloride solution, and then extracted with dichloromethane, concentrated by vacuum distillation to remove the solvent, dried, and the crude product was separated by column chromatography to obtain the target product with a yield of 85%. 1 H NMR(400MHz, CDCl3)δ9.39(s,1H),8.12(dd,J=8.0,1.4Hz,1H),7.46(d,J=7.9Hz,2H),7.36–7.25(m,4H),7.20(t,J=7.6Hz,1 H),7.12(d,J=7.3Hz,1H),6.87(d,J=8.5Hz,1H),6.74(t,J=7.5Hz,1H),5.42(s,2H),2.47(s,3H),2.43(s,3H),2.29(s,3H). 13 C NMR (101MHz, CDCl3) δ168.4,149.5,138.7,138.1,137.9,134.1,133.1,132.4,131. 5,129.2,128.2,126.7,125.9,123.0,116.0,113.6,110.7,66.1,21.2,20.6,14.0.

[0114] Synthesis example 28

[0115] Synthesis of Methothrin

[0116] 0.24mmol 4-(methoxymethyl)benzaldehyde, 0.2mmol 2,2-dimethyl-3-(2-methylpropane-1-en-1-yl)cyclopropane-1-carboxylic acid, 0.4mmol cesium carbonate, 0.24mmol diphenylphosphine oxide and 1ml N,N-dimethylformamide were added to the reaction container. The reaction was stirred at 120°C for 12h under nitrogen atmosphere, and the reaction was stopped, cooled to room temperature, washed with saturated ammonium chloride solution, and then extracted with dichloromethane, concentrated by vacuum distillation to remove the solvent, dried, and the crude product was separated by column chromatography to obtain the target product with a yield of 81%. 1H NMR (400MHz, CDCl3) δ7.34(t,J=5.5Hz,4H),5.12(t,J=8.8Hz,2H),4.88(d,J=7.8Hz,1H),4.45(s,2H), 3.38(s,3H),2.10–2.04(m,1H),1.70(d,J=4.9Hz,6H),1.44(d,J=5.4Hz,1H),1.26(s,3H),1.12(s,3H). 13 C NMR (101MHz, CDCl3) δ172.4,138.1,135.8,135.6,128.3,127.8,121.1,74.4,65.9,58.1,34.8,32.9,28.8,25.5,22.2,20.5,18.5.

[0117] Synthesis Example 29

[0118] Synthesis of 3-phenoxybenzyl (1S, 3S)-2,2-dimethyl-3-(2-methylpropane-1-en-1-yl) cyclopropane-1-carboxylate

[0119] 0.24mmol of m-phenoxybenzaldehyde, 0.2mmol of 2,2-dimethyl-3-(2-methylpropane-1-ene-1-yl)cyclopropane-1-carboxylic acid, 0.4mmol of cesium carbonate, 0.24mmol of diphenylphosphine oxide and 1ml of N,N-dimethylformamide were added to the reaction container. The reaction was stirred at 120°C for 12h under nitrogen atmosphere, and the reaction was stopped, cooled to room temperature, washed with saturated ammonium chloride solution, and then extracted with dichloromethane, concentrated by vacuum distillation to remove the solvent, dried, and the crude product was separated by column chromatography to obtain the target product with a yield of 74%. 1 HNMR (400MHz, CDCl3) δ7.39–7.30(m,3H),7.15–7.07(m,2H),7.02(d,J=7.7Hz,3H),6.95(dd,J=8.1,2.4Hz,1H),5.09(s,2H) ,4.90(d,J=7.8Hz,1H),2.08(dd,J=7.5,5.7Hz,1H),1.70(t,J=6.8Hz,6H),1.45(d,J=5.4Hz,1H),1.26(s,3H),1.13(s,3H). 13C NMR(101MHz,CDCl3)δ172.3,157.5,157.0,138.4,135.6,129.8,123.4,122.6,121.0,119.0,118.9,118.3,118.2,65.6,34.7,32.9,28.8,25.5,22.1,20.4,18.5。

Claims

1. A method for directly preparing carboxylic acid ester compounds from aromatic aldehydes, ketones and carboxylic acids, characterized in that: The synthetic raw materials of the carboxylic acid ester compound include: aromatic aldehyde, ketone compound, secondary amine, diaryl phosphine oxide, base and solvent; The carboxylic acid ester compound has the following structural formula: In the structural formula, R 1 is a substituent at any one or more positions on the benzene ring, and R 1 R is independently selected from one of H, alkyl, alkoxy, aryl, halogen, and difluoromethoxy; 2 One selected from H or alkyl; R 3 One selected from an alkyl group or an aryl group.

2. The method according to claim 1, characterized in that In the structural formula, R 1 is a substituent at any one or more positions on the benzene ring, and R 1 R is independently selected from one of H, methyl, tert-butyl, methoxy, phenyl, fluorine, chlorine, bromine, and difluoromethoxy; 2 One selected from H, methyl; R 3 One selected from butyl, cyclobutyl, adamantyl, benzyl, phenyl, 1-naphthyl, 2-naphthyl, pyrenyl, pyridyl, benzothienyl and quinolyl.

3. The method according to claim 1 or 2, characterized in that The aromatic aldehyde and ketone compound is selected from benzaldehyde, p-methylbenzaldehyde, p-tert-butylbenzaldehyde, p-fluorobenzaldehyde, p-chlorobenzaldehyde, p-bromobenzaldehyde, p-methoxybenzaldehyde, p-phenylbenzaldehyde, o-methylbenzaldehyde, m-chlorobenzaldehyde, 2-fluoro-4-methoxybenzaldehyde, 4-(methoxymethyl)benzaldehyde, 3-phenoxybenzaldehyde, 3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzaldehyde, and acetophenone.

4. The method according to claim 1 or 2, characterized in that: The carboxylic acid is selected from the group consisting of n-pentanoic acid, 2-ethylbutyric acid, cyclobutylcarboxylic acid, adamantanecarboxylic acid, tiglic acid, 5-norbornene-2-carboxylic acid, 4-phenylbutyric acid, p-methoxyphenylacetic acid, p-chlorophenylacetic acid, p-bromophenylacetic acid, o-methylbenzoic acid, o-chlorobenzoic acid, p-fluorobenzoic acid, p-chlorobenzoic acid, p-bromobenzoic acid, p-phenoxybenzoic acid, p-dimethylaminobenzoic acid, p-methylmercaptobenzoic acid, p-trifluoromethoxybenzoic acid, p-trifluoromethylbenzoic acid, 4-[4-(2-(2-methyl-2-ol)-pyrrolidone] ... -(hydroxymethyl)benzoic acid, 4-methyl-1-naphthoic acid, 6-methoxy-2-naphthoic acid, 1-pyrenecarboxylic acid, 6-trifluoromethyl-pyridine-2-carboxylic acid, benzothiophene-3-carboxylic acid, quinoline-5-carboxylic acid, ibuprofen, naproxen, fenofibric acid, gemfibrozil, probenecid, mefenamic acid, flunilic acid, 2,2-dimethyl-3-(2-methylpropane-1-en-1-yl)cyclopropane-1-carboxylic acid, and one of flurbiprofen.

5. The method according to claim 1 or 2, characterized in that: The following steps are involved: Aromatic aldehyde, ketone compound, carboxylic acid, diarylphosphine oxide and base are added to a reaction container in sequence and mixed; a solvent is added under an inert gas atmosphere, and heating and stirring are performed. After the reaction is completed, the mixture is cooled to room temperature, washed with saturated ammonium chloride, and then extracted with dichloromethane, dried with anhydrous sodium sulfate, and the organic solvent is removed by distillation under reduced pressure. The crude product is separated by column chromatography to obtain a carboxylate product.

6. The method according to claim 5, characterized in that The diarylphosphine oxide is selected from one of diphenylphosphine oxide, bis(4-methylphenyl)phosphine oxide and bis(4-chlorophenyl)phosphine oxide.

7. The method according to claim 5, characterized in that The base is selected from one of cesium carbonate, potassium phosphate, sodium carbonate and potassium tert-butoxide.

8. The method according to claim 5, characterized in that The molar ratio of the aromatic aldehyde, the ketone compound, the carboxylic acid, the diaryl phosphine oxide and the base is (1-3):1:(1-3):(1-5).

9. The method according to claim 5, characterized in that The solvent is one of N,N-dimethylformamide, dimethyl sulfoxide, acetonitrile, ethyl acetate and 1,4-dioxane.

10. The method according to claim 5, characterized in that The reaction temperature is 70-130° C.; the reaction time is 8-24 hours; and the inert gas is nitrogen.

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