Method for preparing aromatic carboxylic acid by electroreductive carboxylation reaction and aromatic carboxylic acid

Abstract

The present invention discloses a method for preparing aromatic carboxylic acids by electroreductive carboxylation reaction and the aromatic carboxylic acids. The method for preparing aromatic carboxylic acids by electroreductive carboxylation reaction of the present invention comprises the following steps: in a CO2 atmosphere, under the condition of energization, an electrocarboxylation reaction occurs between a compound containing an aryl group and an electrolyte in a solvent, and after-treatment is carried out to obtain the aromatic carboxylic acid compound; this method directly carboxylates the aromatic C-H through electrocatalytic CO2 reduction activation, has remarkable and unique regioselectivity, and various structurally novel and useful aryl carboxylic acids have been successfully synthesized from different compounds containing aryl groups, and these aryl carboxylic acids are not easily obtained by traditional methods. This electrochemical synthesis method has the characteristics of mild reaction conditions, clean and green, and simple reaction operation.

Description

Technical Field

[0001] The present invention relates to the technical field of organic electrochemistry synthesis. Further, it relates to a method for preparing aromatic carboxylic acids by electroreductive carboxylation reaction and the aromatic carboxylic acids. Background Art

[0002] Aryl carboxylic acids themselves are important scaffolds and key synthetic precursors in organic chemistry, materials science, and medicinal chemistry, and their value has attracted great interest. Many new methods for preparing aryl carboxylic acids have been reported. Among them, the direct carboxylation of aromatic compounds with CO2 is a relatively simple and effective method. The direct C-H carboxylation of arenes would be an ideal route for the synthesis of aryl carboxylic acids.

[0003] However, in addition to the general problems that need to be improved, the chemoselectivity and regioselectivity of the reaction are crucial. At the same time, electrosynthesis has been identified as a relatively ideal route to avoid using stoichiometric redox reagents in organic synthesis. Therefore, the combination of carboxylation and electrosynthesis has attracted considerable attention. Summary of the Invention

[0004] To solve the problems in the prior art, the present invention provides a method for preparing aromatic carboxylic acids by electroreductive carboxylation reaction and the aromatic carboxylic acids. The present invention selects substrates (compounds containing aryl groups) with remarkable and unique regioselectivity, and directly carboxylates the C-H in the compounds containing aryl groups through electrocatalytic CO2 reduction activation. Moreover, a variety of structurally novel and useful aryl carboxylic acids have been successfully synthesized from different substrates, and these aryl carboxylic acids are not easily obtained by traditional methods. This electrochemical synthesis method has the characteristics of mild reaction conditions, clean and green, and simple reaction operation.

[0005] One of the objectives of the present invention is to provide a method for preparing aromatic carboxylic acids by electroreductive carboxylation reaction, comprising the following steps:

[0006] In a CO2 atmosphere, under the condition of energization, a compound containing an aryl group and an electrolyte undergo an electrocarboxylation reaction in a solvent, and after-treatment is carried out to obtain the aromatic carboxylic acid compound;

[0007] The compound containing an aryl group has the following general structural formula:

[0008]

[0009] In Formula 1, Ar is an aryl group;

[0010] R is a cyano group, an alkyl group with 1 - 10 carbon atoms, a substituted or unsubstituted aryl group, Arylamino; R1 is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group; R2 is a substituted or unsubstituted alkyl group, a substituted or unsubstituted aryl group, a halogen; or R2 is connected to the adjacent oxygen atom to form a ring;

[0011] n is any integer from 0 to 4;

[0012] Preferably, the Ar is phenyl, naphthyl, anthryl, phenanthryl, nitrogen-containing heteroaryl, oxygen-containing heteroaryl, sulfur-containing heteroaryl.

[0013] In the method for preparing aromatic carboxylic acid by electroreductive carboxylation reaction of the present invention, preferably,

[0014] The compound containing an aryl group has the following general structural formula:

[0015]

[0016] In Formula 2, R is cyano, C1-C10 alkyl, aryl; R1 is C1-C30 substituted or unsubstituted alkyl, C1-C30 substituted or unsubstituted alkenyl;

[0017] n is any integer from 0 to 3; preferably,

[0018] In Formula 2, R is cyano, C1-C5 alkyl, naphthyl; R1 is C1-C20 substituted or unsubstituted alkyl, C1-C20 substituted or unsubstituted alkenyl; n is any integer from 0 to 2;

[0019] More preferably,

[0020] The compound containing an aryl group is selected from at least one of the following compounds:

[0021]

[0022] In the method for preparing aromatic carboxylic acid by electroreductive carboxylation reaction of the present invention, preferably,

[0023] In Formula 1, Ar is thienyl, benzothienyl, dibenzothienyl, bithienyl;

[0024] R is cyano, C1-C10 alkyl, thienyl, substituted or unsubstituted aryl;

[0025] n is any integer from 0 to 3; preferably,

[0026] R is cyano, C1-C5 alkyl, thienyl, phenyl;

[0027] n is any integer from 0 to 2;

[0028] Further preferably, the aryl-containing compound is selected from at least one of the following compounds:

[0029]

[0030] In the method for preparing aromatic carboxylic acid by electroreductive carboxylation reaction of the present invention, preferably,

[0031] In Formula 1, Ar is furyl or dibenzofuryl;

[0032] R is R1 is a substituted or unsubstituted alkyl group having 1 to 10 carbon atoms;

[0033] n is any integer from 0 to 3; preferably,

[0034] R1 is an alkyl group having 1 to 5 carbon atoms;

[0035] n is any integer from 0 to 2;

[0036] Further preferably, the aryl-containing compound is selected from at least one of the following compounds:

[0037]

[0038] In the method for preparing aromatic carboxylic acid by electroreductive carboxylation reaction of the present invention, preferably,

[0039] In Formula 1, Ar is pyridyl or indolyl;

[0040] R is cyano, halogen, an alkyl group having 1 to 10 carbon atoms, an alkoxy group, a substituted or unsubstituted aryl group;

[0041] n is any integer from 0 to 3; preferably,

[0042] R is cyano, F, an alkyl group having 1 to 5 carbon atoms, an alkoxy group having 1 to 5 carbon atoms, phenyl, phenyl substituted with an alkoxy group having 1 to 5 carbon atoms, pyridyl substituted with an alkoxy group having 1 to 5 carbon atoms, phenyl substituted with an alkyl group having 1 to 5 carbon atoms;

[0043] n is any integer from 0 to 2;

[0044] Further preferably, the aryl-containing compound is selected from at least one of the following compounds:

[0045]

[0046] In the method for preparing aromatic carboxylic acid by electroreductive carboxylation reaction of the present invention, preferably,

[0047] In Formula 1, Ar is phenyl;

[0048] R is an alkoxy group, an aryloxy group, a substituted or unsubstituted aryl group, an alkyl group having 1 to 10 carbon atoms, an arylamino group, wherein, R1 is a substituted or unsubstituted alkyl group; R2 is a substituted or unsubstituted alkyl group or R2 and the oxygen atom adjacent to it form a ring;

[0049] n is any integer from 0 to 3; preferably,

[0050] R is an alkoxy group having 1 to 5 carbon atoms, a phenoxy group, a phenyl group, an alkyl-substituted phenyl group, an alkyl group having 1 to 5 carbon atoms, an arylamino group, wherein, R1 is an alkyl group having 1 to 5 carbon atoms; R2 is an alkyl group having 1 to 5 carbon atoms or R2 and the oxygen atom adjacent to it form a six-membered ring;

[0051] n is any integer from 0 to 2;

[0052] More preferably, the compound containing an aryl group is selected from at least one of the following compounds:

[0053]

[0054] In the method for preparing aromatic carboxylic acid by electroreductive carboxylation reaction of the present invention, preferably,

[0055] The compound containing an aryl group is selected from at least one of the following compounds:

[0056]

[0057]

[0058] In the method for preparing aromatic carboxylic acid by electroreductive carboxylation reaction of the present invention, preferably,

[0059] The electrolyte is selected from at least one of halogen salts; and / or,

[0060] The solvent is selected from at least one of amide solvents, nitrile solvents, and sulfoxide solvents; and / or,

[0061] The molar ratio of the electrolyte to the compound containing an aryl group is 50%-100%:1;

[0062] The concentration of the compound containing an aryl group in the solvent is 0.75-1 mol / L;

[0063] Preferably, the halogen salt is selected from at least one of tetraalkylhalogen salts; and / or,

[0064] The solvent is selected from at least one of N,N-dimethylformamide, N,N-dimethyl sulfoxide, and acetonitrile

[0065] More preferably, the tetraalkyl halide salt is selected from at least one of tetraethylammonium iodide and tetrabutylammonium bromide.

[0066] In the method for preparing aromatic carboxylic acid by electroreductive carboxylation reaction of the present invention, preferably,

[0067] During the electrocarboxylation reaction, a constant current is passed. Preferably,

[0068] The constant current is 1 - 30 mA; and / or,

[0069] The power-on reaction time is 8 - 20 h; and / or,

[0070] The power-on reaction temperature is -10 - 25 °C; and / or,

[0071] More preferably, the constant current is 10 - 25 mA; and / or,

[0072] The power-on reaction time is 6 - 14 h; and / or,

[0073] The power-on reaction temperature is -10 - 15 °C; and / or,

[0074] During the electrocarboxylation reaction, among the electrodes used, the cathode material is selected from graphite felt, nickel foam, cobalt, niobium, platinum sheet; the anode material is selected from graphite felt; and / or,

[0075] The post-treatment includes acidification, extraction, and column chromatography;

[0076] During acidification, the concentration of the acid used is 1 - 2 mol / L. Preferably, the acid used is hydrochloric acid.

[0077] More preferably, the product is carboxylate salt. After post-treatment, first acidify, and then extract from the aqueous phase with ethyl acetate.

[0078] The second object of the present invention is to provide the aromatic carboxylic acid prepared by the method for preparing aromatic carboxylic acid by electroreductive carboxylation reaction described in the first object of the present invention. The aromatic carboxylic acid has the following general structural formula:

[0079]

[0080] In Formula 3, Ar, R, and n are respectively the same as Ar, R, and n described in one of the objects of the present invention;

[0081] Preferably, the aromatic carboxylic acid is:

[0082]

[0083]

[0084] A third object of the present invention is to provide the use of the aromatic carboxylic acid prepared by the method described in one of the objects of the present invention or the aromatic carboxylic acid described in the second object of the present invention as a substrate for synthesizing drug molecules containing aromatic carboxylic acid derivatives.

[0085] The reaction mechanism of the present invention is as follows:

[0086] The reaction of the present invention may be directly initiated by the reduction of the aryl-containing compound on the cathode, forming the corresponding radical anion Int-1 (1, E 1 / 2 =-2.3V, DMF vs Ag / Ag + ). Then, Int-1 reacts with carbon dioxide to form Int-2 (path A). However, the difficulty of the present invention lies in the selection of a suitable substrate (aryl-containing compound), because the structure of the substrate determines its inherent electronic properties, which also determines its unique high regioselectivity. Subsequently, Int-2 is oxidized by iodine and loses H + to generate Int-3, which may also be caused by aromatization. And it is also possible that Int-2 is directly oxidized at the anode and loses H + to generate Int-3. Finally, protonation generates the target carboxylic acid product. At the same time, Et4NI will be oxidized at the anode, avoiding the sacrificial anode. On the other hand, for substrates with a reduction potential more negative than CO2 (such as E 1 / 2 =-2.2V in DMF, -2.3V in CH3CN and SCE), the formation of Int-2 may come from the reaction of the aryl-containing compound with the CO2 radical anion, which is generated by the electroreduction of CO2 at the cathode (path B).

[0087]

[0088] In the ranges and any values disclosed in the present invention, the endpoints and any values are not limited to the exact ranges or values. These ranges or values should be understood to include values close to these ranges or values. For numerical ranges, the endpoint values of each range, between the endpoint values of each range and individual point values, and between individual point values can be combined with each other to obtain one or more new numerical ranges, and these numerical ranges should be regarded as specifically disclosed herein. In the following text, in principle, the various technical solutions can be combined with each other to obtain new technical solutions, which should also be regarded as specifically disclosed herein.

[0089] Compared with the prior art, the present invention has at least the following advantages:

[0090] By adjusting the magnitude of the current and the electrode material of the anode, the present invention can selectively electrolyze the reaction substrate. It can be simultaneously applicable to poly-substituted benzene rings, fused rings, heterocycles, etc., and is compatible with ester groups and amides to obtain aromatic carboxylic acids in relatively high yields.

[0091] The method of the present invention has a high tolerance for substrate functional groups. For different substituents, whether electron-withdrawing groups or electron-donating groups, it shows good reactivity, and the target products have high yields and selectivities. Moreover, it also shows good compatibility with complex late-modified drug molecules and natural products.

[0092] In summary, the present invention: a) converts C-H in a compound directly containing an aryl group into high-value-added organic small molecules through carboxylation; b) has high chemoselectivity and exclusive regioselectivity of the substrate; c) uses electrochemistry as an efficient and scalable preparation technology, showing prospects for industrial application; (d) the preparation method of the present invention is applied to the post-modification carboxylation of natural products and drug derivatives. The electrochemical synthesis method of electrochemically opening and carboxylating the reaction substrate of the present invention has the characteristics of mild reaction conditions, clean and green, and simple reaction operation. Detailed implementation manners

[0093] The present invention will be specifically described below in conjunction with specific embodiments. It is necessary to point out here that the following embodiments are only used for further illustration of the present invention and cannot be construed as limiting the protection scope of the present invention. Some non-essential improvements and adjustments made by those skilled in the art based on the content of the present invention still fall within the protection scope of the present invention.

[0094] In addition, it should be noted that the various specific technical features described in the following detailed implementation manners can be combined in any suitable manner without contradiction. To avoid unnecessary repetition, the present invention will not separately describe various possible combination methods.

[0095] Furthermore, any combination can be made between various different embodiments of the present invention as long as it does not violate the idea of the present invention. The technical solutions formed thereby belong to a part of the original public content of this specification and also fall within the protection scope of the present invention.

[0096] If there is no special limitation on the raw materials used in the examples and comparative examples, they are all disclosed in the prior art. For example, they can be directly purchased or prepared according to the preparation methods disclosed in the prior art.

[0097] Example 1

[0098] In a 15 mL reaction tube, the electrodes were fixed: both the cathode and the anode were graphite felt (GF, 10 mm × 15 mm × 5 mm). A compound containing an aryl group (0.3 mmol, 1.0 equivalent), Et4NI (77.2 mg, 0.3 mmol, 1.0 equivalent), and a magnetic stir bar were added to the reaction tube. Then, the gas was evacuated and replaced three times under a CO2 atmosphere, and anhydrous DMF (4.0 mL) was added using a syringe. At a constant current of 20.0 mA and 0 °C, a CO2 balloon was added, and the reaction was carried out for 10 hours. After the reaction was completed, the reaction mixture was acidified with an aqueous hydrochloric acid solution (2.0 N). After extraction with EtOAc (8 × 15 mL), it was washed with saturated NH4Cl, dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography to afford the desired product.

[0099] The results of the aromatic carboxylic acids in Example 1 are as follows:

[0100] The compounds containing an aryl group are as follows:

[0101]

[0102] The results of the aromatic carboxylic acids prepared in Example 1 are as follows:

[0103]

[0104] As can be seen from the above, functional groups that are quite sensitive to the electroreduction conditions, such as aromatics containing an ester group at the 2-position of the naphthalene ring (1a - 1m), can smoothly produce the desired products, indicating that the electroreduction process has good functional group compatibility. In addition, heterocyclic compounds such as thiophene (2q - 2s), benzothiophene (2t - 2v), furan (2w - 2y), benzofuran (2z), and heteroaromatic rings (2aa - 2aj) can all give carboxylated products in high yields. It is worth noting that this method is also applicable to simple polysubstituted benzene rings (2ak - 2at).

[0105] Examples 2 - 15

[0106] Gram-scale experiment:

[0107]

[0108] The reaction conditions were changed and the yields were compared.

[0109] Reaction conditions: reaction substrate 1 (0.3 mmol), tetraethylammonium iodide (0.3 mmol), N,N-dimethylformamide (4 mL), graphite felt as the cathode, graphite felt as the anode, constant current electrolysis at 0 °C (I = 20 mA).

[0110]

[0111] The reaction conditions and their yields are shown in the following table:

[0112] Table 1

[0113]

[0114]

[0115] The yields in Table 1 above are isolated yields.

[0116] As can be seen from Table 1 above, the yield corresponding to aromatic carboxylation under the reaction conditions of the present invention is as high as 87%. A series of control experiments show that reducing the amount of the electrolyte Et4NI or replacing it with other electrolytes will significantly reduce the yield. Using acetonitrile, dimethyl sulfoxide, etc. as reaction solvents, the reaction effect is not good. Except that the yield is 74% when platinum sheet is used as the cathode material, other cathode materials such as nickel foam, cobalt, niobium, etc. have poor reaction effects. In addition, control experiments show that no carboxylation product is formed without electricity or without introducing CO2.

[0117] The parameters of some carboxylation products synthesized in the present invention are as follows

[0118]

[0119] Product 2a, property: white solid

[0120] 1 H NMR(DMSO-d6,400MHz)δ=8.93(d,J=8.6Hz,1H),8.84(s,1H),8.59(s,1H),8.25(d,J=8.2Hz,1H),7.82–7.78(m,1H),7.71–7.67(m,1H),3.94(s,3H). 13 C NMR(DMSO-d6,100MHz)δ=168.4,166.1,135.5,133.4,133.0,130.8,130.7,129.0,128.9,127.7,126.3,126.1,53.0.HRMS(ESI,m / z):Calculated C 13 H9O4 - [M-H] - :229.0501,found229.0503.

[0121]

[0122] Product 2b, property: white solid

[0123] 11H NMR (DMSO-d6, 400 MHz) δ = 13.69 (s, 1H), 8.86 (d, J = 8.6 Hz, 1H), 8.81 (s, 1H), 8.29 (s, 1H), 8.15 (d, J = 8.1 Hz, 1H), 7.87–7.83 (m, 1H), 7.77–7.73 (m, 1H). 13 13C NMR (DMSO-d6, 100 MHz) δ = 167.7, 139.1, 133.1, 132.2, 131.3, 130.2, 130.0, 129.9, 128.4, 126.2, 118.8, 108.2. HRMS (ESI, m / z): Calculated C 12 17H6NO2 - [M-H] - : 196.0399, found 196.0402.

[0124]

[0125] Product 2c, property: white solid

[0126] 1 1H NMR (DMSO-d6, 400 MHz) δ = 13.06 (s, 1H), 8.63 (s, 1H), 8.02 (s, 1H), 7.90–7.87 (m, 2H), 7.46 (d, J = 8.5 Hz, 1H), 3.06 (quint, J = 6.7 Hz, 2H), 1.29 - 1.27 (m, 12H). 13 13C NMR (DMSO-d6, 100 MHz) δ = 169.3, 147.2, 144.3, 133.0, 130.1, 129.9, 129.2, 128.8, 128.0, 126.1, 122.1, 34.5, 33.6, 24.3, 24.1. HRMS (ESI, m / z): Calculated C 17 18H 19 10O2 - [M-H] - : 255.1385, found 255.1393.

[0127]

[0128] Product 2d, property: white solid

[0129] 11H NMR (DMSO-d6, 400 MHz) δ = 13.47 (s, 1H), 8.92 (d, J = 8.7 Hz, 1H), 8.87 (s, 1H), 8.60 (d, J = 1.8 Hz, 1H), 8.28 (d, J = 8.1 Hz, 1H), 7.83–7.79 (m, 1H), 7.71–7.68 (m, 1H), 7.53 (d, J = 7.0 Hz, 2H), 7.46–7.42 (m, 2H), 7.40–7.36 (m, 1H), 5.45 (s, 2H). 13 13C NMR (DMSO-d6, 100 MHz) δ = 168.4, 165.5, 136.5, 135.6, 133.4, 133.1, 130.9, 130.7, 129.1, 129.0, 128.9, 128.74, 128.69, 127.7, 126.3, 126.1, 67.1. HRMS (ESI, m / z): Calculated C 19 H 13 O4 - [M-H] - : 305.0814, found 305.0816.

[0130]

[0131] Product 2e, property: white solid

[0132] 1 1H NMR (400 MHz, CDCl3) δ = 9.10 (d, J = 8.7 Hz, 1H), 8.96 (d, J = 1.6 Hz, 1H), 8.82 (s, 1H), 8.04 (d, J = 8.1 Hz, 1H), 7.79–7.75 (m, 1H), 7.65–7.62 (m, 1H), 5.37 (quint, J = 6.3 Hz, 1H), 1.46 (d, J = 6.3 Hz, 6H). 13 13C NMR (100 MHz CDCl3) δ = 172.0, 165.3, 136.8, 133.4, 133.3, 131.1, 130.3, 130.2, 127.11, 127.06, 126.0, 69.1, 22.00. HRMS (ESI, m / z): Calculated C 15 H 13 O4 - [M-H] - : 257.0814, found 257.0816.

[0133]

[0134] Product 2f, property: white solid

[0135] 1 H NMR(400MHz,CDCl3)δ=9.11(d,J=8.7Hz,1H),8.96(s,1H),8.83(s,1H),8.06(d,J=8.1Hz,1H),7.80–7.76(m,1H),7.67–7.63(m,1H),5.34–5.29(m,1H),4.10–4.05(m,2H),3.71–3.66(m,2H),2.15–2.12(m,2H),1.98–1.89(m,2H). 13 C NMR(100MHz,CDCl3)δ=171.6,165.0,136.8,133.5,133.3,130.9,130.5,130.2,127.2,126.6,126.2,126.0,70.3,65.4,31.9.HRMS(ESI,m / z):Calcd for C 17 H 15 O5 - [M-H] - :299.0920,found 299.0925.

[0136]

[0137] Product 2g, property: white solid

[0138] 1 H NMR(400MHz,DMSO-d6)δ13.44(s,1H),8.92(d,J=8.7Hz,1H),8.78(s,1H),8.59(d,J=1.8Hz,1H),8.25(d,J=8.0Hz,1H),7.81–7.77(m,1H),7.71–7.67(m,1H),2.33–2.29(m,2H)1.61–1.55(m,10H),1.30–1.28(m,1H).13C NMR(100MHz,DMSO-d6)δ=168.5,164.5,135.2,133.4,132.3,130.8,130.5,129.0,128.7,127.9,127.6,126.0,83.2,36.5,25.9,25.2,22.2.HRMS(ESI,m / z):Calcd for C 19 H 19 O4 - [M-H] -: 311.1284, found 311.1285.

[0139]

[0140] The product was obtained in 2 h, property: white solid

[0141] 1 H NMR (400 MHz, DMSO-d6) δ = 13.46 (s, 1H), 8.93 (d, J = 8.6 Hz, 1H), 8.84 (s, 1H), 8.61 (d, J = 1.5 Hz, 1H), 8.30 (d, J = 8.2 Hz, 1H), 7.83–7.79 (m, 1H), 7.72–7.68 (m, 1H), 4.00 (s, 2H), 2.00 (s, 3H), 1.74 - 1.65 (m, 12H). 13 C NMR (100 MHz, DMSO-d6) δ = 168.4, 165.7, 135.4, 133.5, 133.1, 130.9, 130.7, 128.9, 127.7, 126.6, 126.1, 74.5, 36.9, 33.7, 27.9. HRMS (ESI, m / z): Calculated C 23 H 23 O4 - [M - H] - : 363.1597, found 363.1600.

[0142]

[0143] The product was obtained in 2i, property: white solid

[0144] 11H NMR (400 MHz, DMSO-d6) δ = 13.45 (s, 1H), 8.93 (d, J = 8.6 Hz, 1H), 8.86 (s, 1H), 8.63 (d, J = 1.7 Hz, 1H), 8.29 (d, J = 8.0 Hz, 1H), 7.83–7.79 (m, 1H), 7.72–7.68 (m, 1H), 4.61 (d, J = 1.3 Hz, 1H), 2.02 - 1.95 (m, 1H), 1.77–1.69 (m, 3H), 1.56 - 1.47 (m, 1H), 1.27 - 1.23 (m, 2H), 1.16 (s, 3H), 1.11 (s, 3H), 0.82 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ = 168.4, 166.0, 135.4, 133.5, 133.1, 130.9, 130.7, 129.0, 128.9, 127.7, 126.5, 126.1, 87.0, 48.6, 48.3, 41.3, 30.0, 26.9, 26.0, 20.6, 19.7. HRMS (ESI, m / z): Calculated C 22 H 23 O4 - [M-H] - : 351.1597, found 351.1600.

[0145]

[0146] Product 2j, property: white solid

[0147] 1 1H NMR (400 MHz, CDCl3) δ = 9.11 (d, J = 8.7 Hz, 1H), 8.97 (d, J = 1.7 Hz, 1H), 8.82 (s, 1H), 8.04 (d, J = 8.1 Hz, 1H), 7.79–7.75 (m, 1H), 7.66–7.62 (m, 1H), 5.90–5.80 (m, 1H), 5.10–5.04 (m, 1H), 5.02–4.99 (m, 1H), 4.44 (t, J = 6.7 Hz, 2H), 2.20–2.15 (m, 2H), 1.91–1.84 (m, 2H), 1.65–1.57 (m, 2H). 1313C NMR (100 MHz, CDCl3) δ = 172.1, 165.8, 138.3, 136.8, 133.4, 133.3, 131.0, 130.3, 130.2, 127.1, 126.6, 126.1, 126.0, 115.0, 65.5, 33.3, 28.2, 25.3. HRMS (ESI, m / z): Calculated C 18 H 17 O4 - [M-H] - : 297.1127, found 297.1131.

[0148]

[0149] Product 2k, property: white solid

[0150] 1 1H NMR (400 MHz, CDCl3) δ = 9.11 (d, J = 8.7 Hz, 1H), 8.96 (d, J = 1.8 Hz, 1H), 8.81 (d, J = 1.7 Hz, 1H), 8.04 (d, J = 8.1 Hz, 1H), 7.79–7.75 (m, 1H), 7.65–7.62 (m 1H), 4.46 (t, J = 6.5 Hz, 2H), 2.33 (td, J = 7.0, 2.6 Hz, 2H), 2.03–1.96 (m, 3H), 1.79–1.72 (m, 2H). 13 13C NMR (100 MHz, CDCl3) δ = 172.3, 165.8, 136.9, 133.4, 133.3, 131.0, 130.4, 130.2, 127.1, 126.5, 126.1, 126.0, 83.8, 68.9, 65.0, 27.7, 25.0, 18.1. HRMS (ESI, m / z): Calculated C 18 H 15 O4 - [M-H] - : 295.0971, found 295.0975.

[0151]

[0152] Product 2l, property: white solid

[0153] 11H NMR (400 MHz, CDCl3) δ = 9.11 (d, J = 8.7 Hz, 1H), 8.99 (d, J = 1.5 Hz, 1H), 8.83 (s, 1H), 8.04 (d, J = 8.1 Hz, 1H), 7.79–7.75 (m, 1H), 7.65–7.61 (m, 1H), 5.54 (t, J = 6.9 Hz, 1H), 4.95 (d, J = 7.1 Hz, 2H), 2.08 (t, J = 7.3 Hz, 2H), 1.81 (s, 3H), 1.54–1.37 (m, 5H), 1.34–1.29 (m, 5H), 1.14–1.01 (m, 7H), 0.88–0.82 (m, 14H). 13 13C NMR (100 MHz, CDCl3) δ = 172.1, 165.8, 143.3, 136.9, 133.4, 133.3, 131.2, 130.3, 130.2, 127.1, 126.8, 126.0, 126.0, 117.9, 62.5, 39.9, 39.3, 37.41, 37.37, 37.3, 36.6, 32.8, 32.7, 29.7, 27.9, 25.0, 24.8, 24.4, 22.7, 22.6, 19.7, 16.5. HRMS (ESI, m / z): Calculated C 32 H 45 O4 - [M-H] - : 493.3318, found 493.3327.

[0154]

[0155] Product 2m, property: white solid

[0156] 1 1H NMR (400 MHz, DMSO-d6) = 13.47 (s, 1H), 8.93 (d, J = 8.1 Hz, 2H), 8.63 (s, 1H), 8.27 (d, J = 8.1 Hz, 1H), 7.83–7.80 (m, 1H), 7.73–7.69 (m, 1H), 4.69–4.66 (m, 2H), 4.53 (d, J = 1.9 Hz, 1H), 4.28 (d, J = 10.8 Hz, 2H), 3.81 (d, J = 12.7 Hz, 1H), 3.66 (d, J = 13.0 Hz, 1H), 1.47 (s, 3H), 1.35 (s, 3H), 1.30 (d, J = 3.8 Hz, 6H). 1313C NMR (100 MHz, DMSO-d6) δ = 168.4, 165.0, 135.9, 133.4, 133.1, 130.9, 129.0, 128.9, 127.7, 126.1, 126.0, 108.8, 108.7, 101.5, 70.4, 69.7, 65.6, 61.1, 26.7, 26.2, 25.6, 24.4. HRMS (ESI, m / z): Calculated for C 24 H 25 O9 - [M-H] - : 457.1499, found 457.1490.

[0157]

[0158] Product 2n, Appearance: White solid

[0159] 1 1H NMR (400 MHz, DMSO-d6) δ = 13.93 (s, 1H), 8.73 (s, 1H), 8.16 (d, J = 8.3 Hz, 2H), 8.05 (d, J = 8.7 Hz, 2H), 7.65–7.56 (m, 4H). 13 13C NMR (100 MHz, DMSO-d6) δ = 170.7, 131.0, 130.2, 129.1, 128.8, 127.5, 127.4, 126.2, 125.3.

[0160]

[0161] Product 2o, Appearance: White solid

[0162] 1 1H NMR (DMSO-d6, 400 MHz) δ = 13.30 (s, 1H), 8.92–8.89 (m, 2H), 8.85 (d, J = 8.3 Hz, 1H), 8.56 (s, 1H), 8.16 (d, J = 7.6 Hz, 1H), 7.8–7.78 (m, 1H), 7.75–7.69 (m, 3H). 13 13C NMR (DMSO-d6, 100 MHz) δ = 168.7, 131.5, 131.3, 130.2, 129.9, 129.7, 129.1, 128.5, 127.4, 127.3, 127.0, 126.9, 126.3, 123.3, 122.9.

[0163]

[0164] Product 2p, Property: White solid

[0165] 1 H NMR(400MHz,DMSO-d6)δ=13.13(s,1H),8.75(s,1H),8.25(d,J=8.1Hz,1H),8.09–8.05(m,2H),7.91(s,1H),7.69–7.65(m,1H),7.63–7.59(m,1H),7.54–7.46(m,3H),7.37–7.33(m,1H),7.25(d,J=8.3Hz,1H),7.19(d,J=8.3Hz,1H). 13 C NMR(100MHz,DMSO-d6)δ=167.8,138.6,137.4,134.5,133.6,133.0,132.4,131.0,130.4,129.1,128.9,128.8,128.3,128.2,127.3,127.1,127.0,126.6,126.14,126.10,126.0.HRMS(ESI,m / z):Calculated C 21 H 13 O2 - [M-H] - :297.0916,found 297.0920.

[0166]

[0167] Product 2q, Property: White solid

[0168] 1 H NMR(400MHz,DMSO-d6)δ=13.29(s,1H),8.65(d,J=1.3Hz,1H),8.22(d,J=1.4Hz,1H). 13 C NMR(100MHz,DMSO-d6)δ=162.6,141.0,139.5,135.2,114.2,110.2.

[0169]

[0170] Product 2r, Property: White solid

[0171] 11H NMR (400 MHz, DMSO-d6) δ = 13.20 (s, 1H), 7.67 (d, J = 3.9 Hz, 1H), 7.64–7.63 (m, 1H), 7.50–7.48 (m, 1H), 7.36 (d, J = 3.9 Hz, 1H), 7.16–7.13 (m, 1H). 13 13C NMR (100 MHz, DMSO-d6) δ = 163.1, 143.3, 135.9, 134.7, 133.0, 129.1, 127.7, 126.4, 125.0.

[0172]

[0173] Product 2s, property: white solid

[0174] 1 1H NMR (400 MHz, DMSO-d6) δ = 13.26 (s, 1H), 8.12 (s, 1H), 7.93 (d, J = 5.3 Hz, 1H), 7.52 (d, J = 5.3 Hz, 1H). 13 13C NMR (100 MHz, DMSO-d6) δ = 163.9, 143.7, 139.1, 136.1, 133.5, 126.6, 120.8.

[0175]

[0176] Product 2t, property: white solid

[0177] 1 1H NMR (400 MHz, DMSO-d6) δ = 13.38 (s, 1H), 8.00 (d, J = 8.0 Hz, 1H), 7.95 (d, J = 7.6 Hz, 1H), 7.55–7.51 (m, 1H), 7.48–7.46 (m, 1H), 2.71 (s, 3H). 13 13C NMR (100 MHz, DMSO-d6) δ = 164.8, 140.4, 140.2, 139.8, 128.3, 127.8, 125.2, 124.4, 123.3, 13.2. HRMS (ESI, m / z): Calculated C 10 H7SO2 - [M-H] - : 191.0167, found 191.0170.

[0178]

[0179] Product 2u, property: white solid

[0180] 1 1H NMR (400 MHz, DMSO-d6) δ = 13.58 (s, 1H), 8.45 (s, 1H), 8.29 (s, 1H), 7.91 (d, J = 5.4 Hz, 1H), 7.78 (d, J = 7.5 Hz, 2H), 7.60 (d, J = 5.4 Hz, 1H), 7.54–7.50 (m, 2H), 7.43–7.40 (m, 1H). 13 13C NMR (100 MHz, DMSO-d6) δ = 167.5, 142.1, 139.9, 138.8, 137.1, 131.5, 129.6, 128.2, 127.5, 126.6, 125.7, 124.2. HRMS (ESI, m / z): Calculated C 15 H9SO2 - [M-H] - : 253.0324, found 253.0319.

[0181]

[0182] Product 2v, property: white solid

[0183] 1 1H NMR (400 MHz, DMSO-d6) δ = 13.59 (s, 1H), 8.63 (d, J = 7.7 Hz, 1H), 8.41 (d, J = 7.1 Hz, 1H), 8.18 (d, J = 7.4 Hz, 1H), 8.06 (d, J = 7.1 Hz, 1H), 7.67–7.63 (m, 1H), 7.57–7.50 (m, 2H). 13 13C NMR (100 MHz, DMSO-d6) δ = 167.6, 140.9, 140.3, 137.0, 134.4, 129.4, 127.9, 126.8, 125.3, 125.2, 123.2, 122.5.

[0184]

[0185] Product 2w, property: white solid

[0186] 1 1H NMR (400 MHz, DMSO-d6) δ = 13.06 (s, 1H), 7.92–7.87 (m, 1H), 7.22–7.18 (m, 1H), 6.64–6.62 (m, 1H). 1313C NMR (100 MHz, DMSO-d6) δ = 159.8, 147.5, 145.4, 118.2, 112.5.

[0187]

[0188] Product 2x, property: white solid

[0189] 1 1H NMR (400 MHz, DMSO-d6) δ = 13.02 (s, 1H), 8.56 (s, 1H), 7.42 (s, 1H), 3.83 (s, 3H). 13 13C NMR (100 MHz, DMSO-d6) δ = 163.3, 158.4, 152.0, 145.2, 122.1, 117.5, 52.6.

[0190]

[0191] Product 2y, property: white solid

[0192] 1 1H NMR (DMSO-d6, 400 MHz) δ = 12.99 (s, 1H), 8.44 (s, 1H), 3.82 (s, 3H), 2.46 (s, 3H). 13 13C NMR (DMSO-d6, 100 MHz) δ = 164.0, 159.4, 151.8, 141.3, 130.8, 121.2, 52.2, 10.4. HRMS (ESI, m / z): Calculated for C8H7O5 - [M - H] - : 183.0294, found 183.0296.

[0193]

[0194] Product 2z, property: white solid

[0195] 1 1H NMR (DMSO-d6, 400 MHz) δ = 13.20 (s, 1H), 8.25–8.19 (m, 3H), 8.00 (d, J = 8.0 Hz, 1H), 7.74 (d, J = 8.2 Hz, 1H), 7.61–7.58 (m, 1H), 7.46–7.42 (m, 1H). 1313C NMR (DMSO-d6, 100 MHz) δ = 168.1, 157.6, 156.0, 130.9, 129.9, 128.6, 125.2, 124.5, 123.8, 123.0, 122.1, 113.5, 113.0.

[0196]

[0197] Product 2aa, property: white solid

[0198] 1 1H NMR (400 MHz, DMSO-d6) δ = 8.66 (d, J = 8.4 Hz, 1H), 8.47 (s, 1H), 8.30 (d, J = 6.9 Hz, 2H), 8.17 (d, J = 8.3 Hz, 1H), 7.88–7.84 (m, 1H), 7.73–7.69 (m, 1H), 7.60–7.54 (m, 3H). 13 13C NMR (100 MHz, DMSO-d6) δ = 167.6, 155.8, 148.4, 137.9, 137.6, 130.2, 130.0, 129.8, 129.0, 127.8, 127.2, 125.4, 123.4, 119.1.

[0199]

[0200] Product 2ab, property: white solid

[0201] 1 1H NMR (400 MHz, DMSO-d6) δ = 8.75 (d, J = 8.3 Hz, 1H), 8.35 (s, 1H), 8.23 (d, J = 8.4 Hz, 1H), 8.02–7.99 (m, 1H), 7.94–7.90 (m, 1H). 13 13C NMR (100 MHz, DMSO-d6) δ = 166.2, 148.3, 138.8, 133.0, 131.6, 131.0, 129.9, 125.8, 125.2, 124.0, 117.2. HRMS (ESI, m / z): Calculated C 11 H5N2O2 - [M-H] - : 197.0351, found 197.0353.

[0202]

[0203] Product 2ac, property: white solid

[0204] 1 1H NMR (400 MHz, DMSO-d6) δ = 13.70 (s, 1H), 8.61–8.55 (m, 1H), 7.30–7.27 (m, 1H). 13 13C NMR (100 MHz, DMSO-d6) δ = 163.9 (d, J C-F = 14.9 Hz), 163.5 (d, J C-F = 7.2 Hz), 161.3 (dd, J C-F = 25.2, 15.3 Hz), 158.7 (d, J C-F = 15.9 Hz), 149.4 (dd, J C-F = 9.3, 1.7 Hz), 112.3 (dd, J C-F = 21.6, 5.5 Hz), 108.0 (d, J C-F = 5.8 Hz), 107.7 (d, J C-F = 6.0 Hz). 19 19F NMR (376 MHz, DMSO-d6) δ = -63.2 (d, J = 8.6 Hz), -63.4 (d, J = 8.5 Hz).

[0205]

[0206] Product 2ad, property: white solid

[0207] 1 1H NMR (400 MHz, DMSO-d6) δ = 13.86 (s, 1H), 8.28–8.25 (m, 6H), 7.59–7.55 (m, 4H), 7.53–7.49 (m, 2H). 13 13C NMR (400 MHz, DMSO-d6) δ = 166.8, 157.3, 141.3, 138.4, 130.1, 129.4, 127.3, 118.1. HRMS (ESI, m / z): Calculated C 18 H 12 NO2 - [M-H] - : 274.0868, found 274.0870.

[0208]

[0209] Product 2ae, property: white solid

[0210] 11H NMR (400 MHz, DMSO-d6) δ = 13.71 (s, 1H), 8.25–8.19 (m, 6H), 7.58–7.54 (m, 2H), 7.52–7.48 (m, 1H), 7.12–7.10 (m, 2H), 3.85 (s, 3H). 13 13C NMR (100 MHz, DMSO-d6) δ = 166.9, 161.1, 157.13, 157.10, 141.1, 138.5, 130.9, 130.0, 129.4, 128.7, 127.2, 117.3, 117.2, 114.8, 55.8. HRMS (ESI, m / z): Calculated C 19 H 14 NO3 - [M-H] - : 304.0974, found 304.0981.

[0211]

[0212] Product 2af, property: white solid

[0213] 1 1H NMR (400 MHz, CDCl3) δ = 8.17 (d, J = 6.8 Hz, 6H), 7.04 (d, J = 8.7 Hz, 4H), 3.89 (d, J = 6.2 Hz, 6H). 13 13C NMR (100 MHz, CDCl3) δ = 170.2, 160.9, 157.5, 138.0, 131.3, 128.4, 116.5, 114.2, 55.4. HRMS (ESI, m / z): Calculated C 20 H 16 NO4 - [M-H] - : 334.1080, found 334.1087.

[0214]

[0215] Product 2ag, property: white solid

[0216] 1 1H NMR (400 MHz, DMSO) δ = 13.62 (s, 1H), 8.08 (d, J = 8.7 Hz, 2H), 7.82 (s, 1H), 7.08–7.04 (m, 3H), 3.99 (s, 3H), 3.82 (s, 3H). 1313C NMR (100 MHz, DMSO-d6) δ = 166.5, 164.3, 160.9, 155.2, 143.0, 130.6, 128.5, 114.7, 111.3, 108.3, 55.7, 53.9. HRMS (ESI, m / z): Calculated C 14 H 12 NO4 - [M-H] - : 258.0767, found 258.0769.

[0217]

[0218] Product 2ah, property: white solid

[0219] 1 1H NMR (400 MHz, CDCl3) δ = 7.55 (s, 1H), 7.42 (s, 1H), 7.27–7.24 (m, 4H), 3.94 (s, 3H), 2.39 (s, 3H). 13 13C NMR (100 MHz, CDCl3) δ = 170.3, 164.0, 158.8, 139.6, 139.2, 136.2, 131.0, 129.7, 128.6, 125.9, 116.1, 109.5, 54.0, 20.7. HRMS (ESI, m / z): Calculated C 14 H 12 NO3-[M-H] - : 242.0817, found 242.0821.

[0220]

[0221] Product 2ai, property: white solid

[0222] 1 1H NMR (400 MHz, DMSO) δ = 13.71 (s, 1H), 8.36 (d, J = 0.9 Hz, 1H), 8.01 (d, J = 7.3 Hz, 1H), 7.90–7.86 (m, 1H), 7.24 (d, J = 1.0 Hz, 1H), 6.92 (d, J = 8.1 Hz, 1H), 4.02 (s, 3H), 3.98 (s, 3H). 1313C NMR (100 MHz, DMSO) δ = 166.4, 164.3, 163.6, 154.2, 152.4, 143.0, 140.6, 114.4, 112.9, 112.2, 111.1, 54.1, 53.5. HRMS (ESI, m / z): Calculated for C 13 H 11 N2O4 - [M - H] - : 259.0719, found 259.0715.

[0223]

[0224] Product 2aj, property: white solid

[0225] 1 1H NMR (400 MHz, DMSO - d6) δ = 13.53 (s, 1H), 9.14 (d, J = 4.8 Hz, 1H), 8.56–8.34 (m, 2H), 7.90 (d, J = 4.8 Hz, 1H), 7.65–7.42 (m, 3H). 13 13C NMR (100 MHz, DMSO - d6) δ = 166.0, 164.2, 160.5, 157.0, 137.1, 131.7, 129.3, 128.4, 119.2. HRMS (ESI, m / z): Calculated for C 11 H7N2O2 - [M - H] - : 199.0508, found 199.0515.

[0226]

[0227] Product 2ak, property: white solid

[0228] 1 1H NMR (400 MHz, DMSO) δ = 13.03 (s, 1H), 7.07–7.04 (m, 2H), 6.74–6.71 (m, 1H), 3.78 (s, 6H). 13 13C NMR (100 MHz, DMSO) δ = 167.4, 160.8, 133.3, 107.3, 105.3, 55.9.

[0229]

[0230] Product 2al, property: white solid

[0231] 1¹H NMR (400 MHz, DMSO) δ = 13.12 (s, 1H), 7.70 (d, J = 7.6 Hz, 1H), 7.51 (t, J = 7.8 Hz, 1H), 7.44–7.41 (m, 3H), 7.30–7.27 (m, 1H), 7.21–7.17 (m, 1H), 7.07 (d, J = 8.3 Hz, 2H). 13 ¹³C NMR (100 MHz, DMSO) δ = 167.1, 157.6, 156.4, 133.1, 130.8, 130.7, 124.6, 124.5, 123.3, 119.8, 118.6.

[0232]

[0233] Product 2am, property: white solid

[0234] 1 ¹H NMR (400 MHz, DMSO) δ = 12.68 (s, 1H), 7.43 (dd, J = 8.4, 2.0 Hz, 1H), 7.38 (d, J = 2.0 Hz, 1H), 6.93 (d, J = 8.4 Hz, 1H), 4.32–4.29 (m, 2H), 4.27–4.26 (m, 2H). ¹³C NMR (100 MHz, DMSO) δ = 167.2, 147.9, 143.5, 124.2, 123.4, 118.6, 117.5, 64.9, 64.3.

[0235]

[0236] Product 2an, property: white solid

[0237] 1 ¹H NMR (400 MHz, DMSO) δ = 12.66 (s, 1H), 7.57 (dd, J = 8.4, 2.0 Hz, 1H), 7.45 (d, J = 2.0 Hz, 1H), 7.00 (d, J = 8.4 Hz, 1H), 3.81 (s, 3H), 3.79 (s, 3H). 13 ¹³C NMR (100 MHz, DMSO) δ = 167.6, 153.1, 148.8, 123.6, 123.4, 112.3, 111.3, 56.0, 55.8.

[0238]

[0239] Product 2ao, property: white solid

[0240] 11H NMR (400 MHz, DMSO) δ = 12.67 (s, 1H), 7.16 (s, 1H), 7.10–7.01 (m, 2H), 3.75 (s, 3H), 3.72 (s, 3H). 13 13C NMR (100 MHz, DMSO) δ = 167.5, 153.0, 152.6, 122.5, 118.8, 115.7, 114.6, 56.8, 56.0.

[0241]

[0242] Product 2ap, property: white solid

[0243] 1 1H NMR (400 MHz, DMSO) δ = 12.94 (s, 1H), 6.87 (s, 2H), 2.23 (s, 9H). 13 13C NMR (100 MHz, DMSO) δ = 171.3, 138.4, 134.1, 133.0, 128.4, 21.1, 19.8.

[0244]

[0245] Product 2aq, property: white solid

[0246] 1 1H NMR (400 MHz, CDCl3) major isomer: δ = 8.77–8.76 (m 1H), 8.29 (dd, J = 7.6, 1.6 Hz, 1H), 8.19–8.12 (m, 1H), 7.57 (t, J = 7.8 Hz, 1H), 4.45–4.39 (m, 2H), 1.44 - 1.40 (m, 3H). 13 13C NMR (100 MHz, CDCl3) δ = 171.26, 171.25, 165.7, 165.6, 135.0, 134.7, 134.2, 132.9, 131.3, 131.1, 130.1, 129.7, 129.6, 128.7, 61.5, 61.4, 14.3, 14.2.

[0247]

[0248] Product 2ar, property: white solid

[0249] 11H NMR (400 MHz, CDCl3) δ = 8.73 (d, J = 1.8 Hz, 1H), 8.12 (dd, J = 8.0, 2.0 Hz, 1H), 7.37 (d, J = 8.0 Hz, 1H), 4.40 (q, J = 7.1 Hz, 2H), 2.72 (s, 3H), 1.41 (t, J = 7.1 Hz, 3H). 13 13C NMR (100 MHz, CDCl3) δ = 171.9, 165.8, 146.4, 133.6, 132.8, 132.2, 128.51, 128.46, 61.2, 22.3, 14.3.

[0250]

[0251] Product 2as, property: white solid

[0252] 1 1H NMR (400 MHz, DMSO) δ = 12.93 (s, 1H), 8.04 (d, J = 2.0 Hz, 1H), 7.71 (dd, J = 8.0, 2.0 Hz, 1H), 7.56 (d, J = 8.1 Hz, 2H), 7.37 (d, J = 8.0 Hz, 1H), 7.28 (d, J = 8.0 Hz, 2H), 2.54 (s, 3H), 2.34 (s, 3H). 13 13C NMR (100 MHz, DMSO) δ = 169.1, 138.2, 138.1, 137.4, 136.7, 132.7, 131.5, 130.1, 129.9, 128.3, 126.8, 21.3, 21.1. HRMS (ESI, m / z): Calculated C 15 H 13 O2 - [M - H] - : 225.0916, found 225.0921.

[0253]

[0254] Product 2at, property: white solid

[0255] 1 1H NMR (400 MHz, CDCl 3) δ = 7.78 (s, 1H), 7.70–7.68 (m, 1H), 7.32–7.30 (m, 3H), 7.28 (d, J = 3.4 Hz, 3H), 7.11–7.04 (m, 6H). 1313C NMR (100 MHz, CDCl3) δ = 171.0, 148.3, 147.3, 130.3, 129.4, 129.3, 128.4, 124.5, 123.7, 123.4. HRMS (ESI, m / z): Calculated C 19 H 14 NO2 - [M-H] - : 288.1025, found 288.1029.

[0256] Example 16

[0257] The aromatic carboxylic acid of the present invention is used as a substrate to synthesize drug molecules containing aromatic carboxylic acid derivatives. Specifically:

[0258]

[0259] The substrate 2aa (i.e., the above compound 28) can be used as a drug molecule containing an aromatic carboxylic acid derivative (compound 28c).

[0260] Other aromatic carboxylic acids in the present invention can also react with corresponding other compounds using the carboxylic acid groups therein, and those skilled in the art can carry out the reaction according to the usage requirements.

[0261] The present invention has been described in detail above in combination with specific embodiments and exemplary examples, but these descriptions should not be construed as limiting the present invention. Those skilled in the art understand that without departing from the spirit and scope of the present invention, various equivalent substitutions, modifications or improvements can be made to the technical solutions and their implementation manners of the present invention, and these all fall within the scope of the present invention. The protection scope of the present invention shall be subject to the appended claims.

[0262] All publications, patent applications, patents and other references mentioned in this specification are hereby incorporated by reference. Unless otherwise defined, all technical and scientific terms used in this specification have the meanings commonly understood by those skilled in the art. In case of conflict, the definitions in this specification shall prevail.

[0263] When this specification uses prefixes such as "well-known to those skilled in the art", "prior art" or their similar terms to derive materials, substances, methods, steps, devices or components, etc., the objects derived by such prefixes cover those commonly used in the art at the time when this application is filed, but also include those that are not commonly used at present but will become commonly recognized in the art as suitable for similar purposes.

[0264] In the context of this specification, any matters or things not mentioned, except for the clearly stated content, shall directly apply those known in the art without any change.

Claims

1. A method for preparing aromatic carboxylic acids by electroreductive carboxylation, characterized in that, It includes the following steps: In a CO2 atmosphere, under the condition of energization, an electrocarboxylation reaction occurs between a compound containing an aryl group and an electrolyte in a solvent, followed by post-treatment to obtain the aromatic carboxylic acid compound; the electrolyte is selected from at least one of halide salts; the halide salt is selected from at least one of tetraethylammonium iodide and tetrabutylammonium bromide; the solvent is selected from at least one of amide solvents, nitrile solvents, and sulfoxide solvents; when performing the electrocarboxylation reaction, a constant current is passed through; The compound containing an aryl group has the general structural formula shown in Formula 1: In Formula 1, Ar is thiophenyl, benzothiophenyl, dibenzothiophenyl, or bithiophenyl; R is cyano, a C1-C10 alkyl group, thiophenyl, or phenyl; n is an arbitrary integer from 0 to 3; Or In Formula 1, Ar is furyl or dibenzofuryl; R is R1 is an alkyl group having 1 to 10 carbon atoms; n is an arbitrary integer from 0 to 3; Or In Formula 1, Ar is pyridyl or indolyl; R is cyano, halogen, a C1-C10 alkyl group, a C1-C5 alkoxy group, phenyl, a phenyl group substituted with a C1-C5 alkoxy group, a pyridyl group substituted with a C1-C5 alkoxy group, or a phenyl group substituted with a C1-C5 alkyl group; n is an arbitrary integer from 0 to 3; Or In Formula 1, Ar is phenyl; R is an alkoxy group having 1 to 5 carbon atoms, a phenoxy group, a phenyl group, an alkyl group having 1 to 10 carbon atoms, wherein, R1 is an alkyl group having 1 to 5 carbon atoms; R2 is an alkyl group having 1 to 5 carbon atoms or R2 and the oxygen atom adjacent thereto are connected to form a six-membered ring; n is an arbitrary integer from 0 to 3; Or The compound shown in Formula 1 has the general structural formula shown in Formula 2: In Formula 2, R is a cyano group, an alkyl group having 1 to 10 carbon atoms, R1 is an alkyl group having 1 to 30 carbon atoms or an alkenyl group having 1 to 30 carbon atoms; n is an arbitrary integer from 0 to 3; The aromatic carboxylic acid compound has the general structural formula shown in Formula 3: In Formula 3, Ar, R, and n respectively correspond to Ar, R, and n in Formula 1 or Formula 2 and are the same; Or The compound containing an aryl group has the following compound:

2. The method for preparing an aromatic carboxylic acid by electroreductive carboxylation according to claim 1, wherein: In Formula 2, R is a cyano group, an alkyl group having 1 to 5 carbon atoms, a naphthyl group; R1 is an alkyl group having 1 to 20 carbon atoms or an alkenyl group having 1 to 20 carbon atoms; n is any integer from 0 to 2.

3. The method for preparing an aromatic carboxylic acid by electroreductive carboxylation according to claim 1, wherein: In Formula 1, Ar is thiophenyl, benzothiophenyl, dibenzothiophenyl, or bithiophenyl; R is cyano, a C1-C5 alkyl group, thiophenyl, or phenyl; n is an arbitrary integer from 0 to 2.

4. The method for preparing an aromatic carboxylic acid by electroreductive carboxylation according to claim 1, wherein: In Formula 1, Ar is furyl or dibenzofuryl; R is R1 is an alkyl group having 1 to 5 carbon atoms; n is an arbitrary integer from 0 to 2.

5. The method for preparing an aromatic carboxylic acid by electroreductive carboxylation according to claim 1, wherein: In Formula 1, Ar is pyridyl or indolyl; R is cyano, F, a C1-C5 alkyl group, a C1-C5 alkoxy group, phenyl, a phenyl group substituted with a C1-C5 alkoxy group, a pyridyl group substituted with a C1-C5 alkoxy group, or a phenyl group substituted with a C1-C5 alkyl group; n is an arbitrary integer from 0 to 2.

6. The method for preparing an aromatic carboxylic acid by electroreductive carboxylation according to claim 1, wherein: In Formula 1, Ar is phenyl; R is C1-C5 alkoxy, phenoxy, phenyl, C1-C5 alkyl, wherein, R1 is C1-C5 alkyl; R2 is C1-C5 alkyl or R2 and the oxygen atom adjacent thereto form a six-membered ring; n is an arbitrary integer from 0 to 2.

7. The method for preparing an aromatic carboxylic acid by electroreductive carboxylation according to claim 1, wherein: The molar ratio of the electrolyte to the compound containing an aryl group is 50%-100%:1; The concentration of the compound containing an aryl group in the solvent is 0.75-1 mol / L.

8. The method for preparing aromatic carboxylic acid by electroreductive carboxylation according to claim 1, characterized in that: The solvent is selected from at least one of N,N-dimethylformamide, dimethyl sulfoxide, and acetonitrile.

9. The method for preparing aromatic carboxylic acid by electroreductive carboxylation according to claim 1, characterized in that: The constant current is 1-30 mA; and / or, The power-on reaction time is 6-20 h; and / or, The power-on reaction temperature is -10-25 °C.

10. The method for preparing aromatic carboxylic acid by electroreductive carboxylation according to claim 9, characterized in that: The constant current is 10-25 mA; and / or, The power-on reaction temperature is -10-15 °C; and / or, During the electrocarboxylation reaction, among the electrodes used, the cathode material is selected from graphite felt, nickel foam, cobalt, niobium, and platinum sheet; the anode material is selected from graphite felt; and / or, The post-treatment includes acidification, extraction, and column chromatography; When acidifying, the concentration of the acid used is 1-2 mol / L.

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