A method for N-phenylindigo-mediated conversion of ketones to carboxylic acids

Abstract

The application provides a kind of N-phenyl indigo mediated ketone-carboxylic acid conversion reaction method, indigo skeleton compound and ketone organic matter are mixed, catalyst and solvent are added therein, reaction is carried out at 80-100 DEG C for 12-24h, quenches reaction, organic layer is dried and rotary evaporated to remove solvent, residue layer chromatography purification is carried out, and carboxylic acid group is simultaneously constructed with active complex functional molecule containing indigo skeleton by one-step reaction;The method overcomes the shortcomings of the need to add excess oxidant, high temperature, noble metal catalyst and the like in the past, raw materials are simple and easy to obtain, reaction conditions are mild and safe, and the reaction product has great potential application value in the field of medicine.

Description

Technical Field

[0001] This invention belongs to the field of preparation of carboxylic acids and their derivatives, specifically relating to an N-phenylindigo-mediated ketone-carboxylic acid conversion reaction method. Background Technology

[0002] 2,3-Diketone indole (isatin) is an excellent oxidized indole, and has received particular attention as a core group in many pharmacologically active compounds. Precise decoration of the indigo framework leads to various privileged molecules, which are being studied as anti-allergic, antimalarial, antibacterial, anti-HIV, and potential antitumor drugs. Furthermore, indigo compounds are important frameworks for drug design, functional materials, and dye development. Due to the synthetic applications of isotines, developing efficient methods for synthesizing these compounds has become a prominent research area.

[0003] Carboxylic acids are an important functional group in organic chemistry and biology, playing a crucial role as a multifunctional building block in the synthesis of natural products, pharmaceuticals, pesticides, polymers, and dyes. In recent decades, chemists have reported numerous methods for preparing carboxylic acids, the most classic being the haloform reaction. As one of the oldest known organic reactions, the haloform reaction produces haloforms under basic conditions and attaches a halogen atom to the methyl group attached to the carbonyl group under acidic conditions. In organic chemistry, it can be used to convert methyl ketones into the corresponding carboxylic acids. Oxidative cleavage of alkenes or alkynes is also one of the fundamental reactions in organic synthesis for constructing carboxylic acids and their derivatives. This usually requires strong oxidants such as potassium permanganate or catalysis using a combination of a suitable oxidant and a metal; however, the reaction conditions are demanding and limit the range of substrates. Oxidation of alcohols and aldehydes is also a commonly used method for synthesizing carboxylic acids and their derivatives. Besides the above methods, conventional synthetic routes for preparing carboxylic acids include the hydrolysis of acyl derivatives, such as acyl halides, acid anhydrides, esters, and amides; and the synthesis of carboxylic acids using carbon dioxide as a carbon source. Despite these advances, these strategies often rely on excessive oxidants, heavy metals, and harsh conditions (e.g., strong oxidants, high temperatures, and the generation of toxic waste), which limits the range of substrates suitable for synthetic purposes. Therefore, the preparation of carboxylic acids and their derivatives under transition metal-free and non-oxidizing conditions presents an attractive yet challenging route. Summary of the Invention

[0004] This invention overcomes the shortcomings of previous methods, such as the need for excessive oxidants, high temperatures, and precious metal catalysis, and provides an N-phenylindigo-mediated ketone-carboxylic acid conversion method. Using indigo-containing skeleton compounds and ketone organics as substrates, and with the action of catalysts such as TfOH and solvents such as cyclohexane, the ketone-carboxylic acid conversion can be efficiently achieved under mild conditions through N-phenylindigo-mediated conversion. This conversion provides a good strategy for synthesizing various active functional molecules containing indigo skeletons and various steroid skeletons.

[0005] To achieve the above objectives, the present invention provides the following technical solution:

[0006] A method for N-phenylindigo-mediated ketone-carboxylic acid conversion involves mixing an indigo-containing skeleton compound and a ketone organic compound, adding a catalyst and solvent, and reacting at 80-100℃ for 12-24 hours to obtain the carboxylic acid organic compound. The reaction process is as follows:

[0007] Furthermore, the indigo skeleton compound can be one of indigo, N-phenylindigo, N-methylindigo, 5-fluoroindigo, 5-methylindigo, 7-methoxyindigo, 4-chloroindigo, 6-chloroindigo, 5,6-dichloroindigo, 5-nitroindigo, and 5,7-dimethylindigo. For example:

[0008] Furthermore, the ketone organic compound is one of aryl ketones, alkyl ketones, or cyclic ketones.

[0009] Furthermore, the ketone organic compound is one of the following: phenylbutanone, 4-methylphenylacetone, 4-ethylphenylacetone, 4-methoxyphenylacetone, 4-benzyloxyphenylacetone, 3-chlorophenylacetone, 4-chlorophenylacetone, 4-trifluoromethylphenylacetone, 4-fluorophenylacetone, 4-hydroxyphenylacetone, 3-nitrophenylacetone, 4-aminophenylacetone, 3-pyridylethyl ketone, 1-(naphthyl-2-yl)prop-1-one, 1-cyclopentyl-prop-1-one, 5-methyl-3-heptanone, 1-tetrahydronaphthone, 2-phenylcyclohexanone, cyclohexanone, cyclopentanone, and cycloheptanone.

[0010] Furthermore, the molar ratio of the indigo-containing skeleton compound to the ketone organic compound is 1:1.2-1.5.

[0011] Furthermore, the catalyst is one of trifluoromethanesulfonic acid, trifluoroacetic acid, p-toluenesulfonic acid, aluminum trichloride, cesium carbonate, sodium bicarbonate, and triethylenediamine.

[0012] Furthermore, the molar ratio of the catalyst to the indigo-containing skeleton compound is 0.8-5.

[0013] Furthermore, the solvent is one of cyclohexane, dimethyl sulfoxide, N,N-dimethylformamide, chloroform, 1,4-dioxane, n-heptane, and dodecane.

[0014] Furthermore, the concentration of the solvent is 0.2-0.3 mol / L.

[0015] Furthermore, the reaction was carried out at 80°C for 16 minutes.

[0016] Compared with the prior art, the advantages and beneficial effects of the present invention are as follows:

[0017] 1. This invention uses compounds containing indigo skeletons and ketone organics as reaction substrates, TfOH as a catalyst, and cyclohexane or DCE as a solvent to construct carboxylic acid groups and active complex functional molecules containing indigo skeletons in a one-step reaction.

[0018] 2. The conversion method of this invention uses inexpensive and readily available raw materials, has a wide substrate range, high atom utilization, simple post-processing, and is green and pollution-free. Under mild reaction conditions, it can efficiently convert ketone organic compounds into carboxylic acids and their derivatives without the need for oxidants. Carboxylic acid derivatives and indigo skeleton compounds have great potential application value in the pharmaceutical field. Thirty carboxylic acid derivatives were synthesized using aryl, heteroaryl, and alkyl ketone compounds as starting materials; twelve active complex functional molecules containing an indigo basic skeleton were synthesized using cyclic ketone compounds as starting materials; and active complex functional molecules containing indigo and steroid skeletons were synthesized using 5α-Pregnane-3,20-dione as starting materials, providing a good strategy for subsequent research. Good yields were achieved regardless of the electronic properties of the substituents, and the method exhibits good functional group tolerance and substrate tolerance. Characterization of the synthesized compounds by 1H NMR, 1C NMR, and high-resolution mass spectrometry showed that the obtained compounds were correct. Detailed Implementation

[0019] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0020] The raw materials for this invention are sourced from the following: trifluoromethanesulfonic acid; trifluoroacetic acid; p-toluenesulfonic acid; aluminum trichloride; hydrochloric acid; sodium hydroxide; cesium carbonate; sodium bicarbonate; 8-diazabicyclo[5.4.0]undec-7-ene; triethylenediamine; cyclohexane; acetonitrile; dimethyl sulfoxide; N,N-dimethylformamide; chloroform; 1,4-dioxane; n-heptane; dodecane; N-phenylindigo; phenylbutanone; 4-methylphenylacetone; 4-ethylphenylacetone ; 4-Methoxyphenylacetone; 4-Benzyloxyphenylacetone; 3-Chlorophenylacetone; 4-Chlorophenylacetone; 4-Trifluoromethylphenylacetone; 4-Fluorophenylacetone; 4-Hydroxyphenylacetone; 3-Nitrophenylacetone; 4-Aminophenylacetone; 3-Pyridylethyl ketone; 1-(Naphthyl-2-yl)prop-1-one; 1-Cyclopentyl-prop-1-one; 5-Methyl-3-heptanone; 1-Tetrahydronaphthone; 2-Phenylocyclohexanone; Cyclohexanone; Cyclopentanone; Cycloheptanone, etc. Reagents used in the experiments were purchased from Saen Chemical Technology (Shanghai) Co., Ltd., Guizhou Platinum Strontium Titanium Chemical Products Co., Ltd., Shanghai BIDE Pharmaceutical Technology Co., Ltd., Shanghai Yuanfan Biotechnology Co., Ltd., Shanghai Aladdin Biochemical Technology Co., Ltd., Shanghai Titan Technology Co., Ltd., etc. Unless otherwise specified, materials were obtained from suppliers. Solvents used, such as ethanol, petroleum ether, methanol, etc., were of analytical grade or prepared according to standard solvent purification methods.

[0021] Table 1

[0022]

[0023]

[0024] Example 1

[0025] This embodiment provides an N-phenylindigo-mediated ketone-carboxylic acid conversion reaction method.

[0026]

[0027] N-Phenylacetin 1 (0.5 mmol, 1.0 eq), phenylbutanone 2 (0.6 mmol, 1.2 eq), and trifluoromethanesulfonic acid (0.75 mmol, 1.5 eq) were added to a sealed reaction tube containing 2.0 mL of cyclohexane. The reaction mixture was stirred at 80 °C for 16 h. Then, 30.0 mL of saturated NaHCO3 was added to quench the reaction. The aqueous layer was extracted with EtOAc (3 × 30.0 mL), and the combined organic layers were dried over anhydrous Na2SO4, followed by solvent removal using a rotary evaporator. The residue was purified by silica gel flash column chromatography (petroleum ether / ethyl acetate = 4:1) to give compound 3. The aqueous phase was adjusted to pH 1 with 1 M HCl, extracted with EtOAc (3 × 30.0 mL), and the combined organic layers were dried over anhydrous Na2SO4, followed by solvent removal using a rotary evaporator. The residue was purified by silica gel flash column chromatography (petroleum ether / ethyl acetate = 2:1) to give compound 4.

[0028] Example 2-Example 21

[0029] The difference from Example 1 is that the catalyst, solvent, reaction temperature, and reaction time were carried out according to Table 1, while other steps were the same. This was to investigate the effects of different catalysts, solvents, and process parameters on the conversion of ketones to carboxylic acids.

[0030] Table 2

[0031]

[0032] Table 2 shows that TfOH, as a catalyst, achieved a product yield as high as 88%; however, using CF3COOH instead of TsOH as a catalyst did not significantly improve the yield; and neither strong inorganic acid salts nor strong bases were used as catalysts to obtain the target compound. These results further demonstrate the decisive role of acid catalysts in the reaction pathway. After studying the solvent effect, the results with other solvents were not superior to those with cyclohexane. The study of the solvent effect showed that alkane solvents were significantly better than other solvents, such as acetonitrile and 1,4-dioxane, in promoting the reaction. When the reaction time was reduced to 16 h, the product yield increased to 94%; however, when the reaction time was extended to 48 h, the yield decreased. When considering the effect of reaction temperature on the reaction yield, it was found that both decreasing and increasing the temperature reduced the yield, and the reaction did not occur at room temperature. Therefore, the optimal temperature for this reaction was determined to be 80℃. To significantly improve the reaction yield, we further evaluated the loading of the catalyst TfOH, adjusting the amount of TfOH to 1.0 eq, 1.2 eq, and 2.0 eq, respectively. We found that the maximum yield was still achieved at 1.5 eq. The effect of different substitutions of indigo at different positions on the reaction was also investigated.

[0033]

[0034] aReactionconditions:TheIsatin1(0.5mmol,1.0eq), Butyrophenone2a(0.6mmol,1.2eq)andTfOH(0.75mmol,1.5eq)was

[0035] addedto2.0mLCyclohexanesealedreactiontubecontaining,thereactionmixturewasstirredat80℃for16h.

[0036] In summary, we determined the optimal conditions as follows: using TfOH (1.5 equiv) as the catalyst, N-phenylindigo at a concentration of (0.5 mmol, 1.0 equiv), phenylbutanone at a concentration of (0.6 mmol, 1.5 equiv), cyclohexane as the solvent, a reaction concentration of 0.25 M, and continuous reaction at 80 °C for 16 hours. Substrate expansion was then conducted under these optimal conditions to explore the applicability of this method.

[0037]

[0038] Under determined optimal conditions, the substrate applicability of aryl, heteroaryl, and alkyl ketones was explored. A series of corresponding products were successfully obtained. Substrates containing both electron-deficient and electron-rich groups reacted well with 4. Various electron-donating groups, such as methyl (4b), ethyl (4c), tert-butyl (4d), and methoxy (4e), showed good tolerance and provided the desired products in yields ranging from 74% to 89%. Furthermore, steric hindrance had almost no effect on the reaction results (4f, yield 87%). Arylacetones with electron-withdrawing groups (F, Cl, and Br) also underwent successful conversion, providing the desired products in moderate to high yields (4g–4i), ranging from 93% to 98%. Encouragingly, a series of disubstituted substrates on the benzene ring worked well, providing opportunities for subsequent conversions (4j–4k) in yields of 83% and 85%, respectively. Surprisingly, arylacetones with strong electron-withdrawing groups (CF3) (4l-4m) also work well, with yields of 73% and 52%, respectively. Encouragingly, arylacetones substituted with hydroxyl (4n), nitro (4o), methylthio (4p), and amino (4q) groups exhibit good functional group tolerance, with yields ranging from 64% to 81%. Notably, arylacetones containing naphthalene ring structures (4r) or biphenyl structures (4s) react successfully with 1, with yields of 86% and 61%, respectively. Furthermore, heteroaryl-substituted arylacetones are also compatible in this scheme, providing the corresponding products (4t-4u) with yields of 71% and 66%, respectively. Various types of alkyl ketones readily react with N-phenylindigo to give the corresponding carboxylic acid products 4 in moderate to high yields (4v-4ad), ranging from 41% to 82%.

[0039] Example 22

[0040] Using 0.5 mmol N-phenylindigo and 0.6 mmol cyclohexanone as reaction substrates, TfOH (1.5 equiv) as catalyst, and cyclohexane as solvent (reaction concentration 0.25 M), the reaction was carried out continuously at 80 °C for 16 h to explore the reaction conditions of cyclic ketones.

[0041]

[0042] 1-Phenylacetin 1 (0.5 mmol, 1.0 eq), cyclohexanone 5 (0.6 mmol, 1.2 eq), and trifluoromethanesulfonic acid (2.5 mmol, 5.0 eq) were added to a sealed reaction tube containing 2.0 mL of dichloroethane. The reaction mixture was stirred at a constant temperature or 80 °C for 6 h. Then, 30.0 mL of H₂O was added to quench the reaction. The aqueous layer was extracted with EtOAc (3 × 30.0 mL), and the combined organic layers were dried over anhydrous Na₂SO₄, followed by solvent removal using a rotary evaporator. The residue was purified by silica gel flash column chromatography (petroleum ether / ethyl acetate = 2:1) to give compound 6.

[0043] Examples 23-34

[0044] The difference from Example 1 is that the amount of catalyst, type of solvent, reaction temperature and reaction time are as shown in Table 3, while the other steps are the same.

[0045] Table 3

[0046]

[0047] As shown in Table 3 above, the target compound was not detected after 16 h of reaction under standard conditions. Subsequently, by adjusting the loading of the catalyst TfOH, we successfully obtained the target compound in a yield of 16%. Encouraged by this positive result, we screened various solvents, such as CHCl3, CCl4, 1,2-Dichloroethane (DCE), and CH3CN, increasing the yield of 6a to 54%. Other reaction parameters, including reaction temperature and reaction time, were also investigated; however, these did not improve the efficiency. In summary, the optimal reaction conditions were determined, as shown in Example 28.

[0048] Examples 35-48

[0049] The reaction was carried out at 80 °C for 16 h with 0.5 mmol N-phenylindigo and 0.6 mmol of different cyclic ketones, using 2.5 mmol of catalyst TfOH and 2.0 mL of cyclohexane as solvent. The specific types of cyclic ketones and reaction yields are as follows:

[0050]

[0051] By testing methylcyclohexanones with different substitution positions (6b-6d), the results showed that the target compound was obtained in moderate to good yields. Subsequently, the effect of steric hindrance on the reaction (6e-6f) was explored, indicating that ortho-substituted cyclic ketones more readily fix the bond-breaking selectivity of the target compound. Furthermore, we tested cyclic ketones of different sizes, such as five-membered rings (6g-6i) and seven-membered rings (6j), with good results. Benzocyclic ketones (6k-6l) were also suitable for this reaction, providing a new method for the construction and transformation of complex active compounds containing indigo skeletons. In addition, we conducted further studies to demonstrate the value of this method in constructing complex functional molecules. 5α-Pregnane-3,20-dione 5m can readily react with N-phenylindigo 1 under mild conditions to obtain the target compound (6m) in 40% yield. This transformation provides a good platform for the synthesis of various functional molecules containing indigo skeletons and various steroidal skeletons.

[0052] All compounds were characterized by proton NMR spectroscopy, carbon NMR spectroscopy, and high-resolution mass spectrometry. The data show that the obtained compounds are correct, and the results are as follows:

[0053]

[0054] Benzoic acid (4a). White solid: 56.4 mg (94%); mp 121.4-122.8°C. 1 H NMR (600MHz, DMSO-d6) δ12.97(s,1H),7.95(d,J=7.8Hz,2H),7.62(t,J=7.4Hz,1H),7.50(t,J=7.6Hz,2H). 13 C NMR(151MHz,DMSO-d6)δ167.3,132.9,130.8,129.3,128.6.HRMS(m / z):[MH] + Calcd.for C7H6O2121.0290; found 121.0303.

[0055]

[0056] 4-methylbenzoic acid(4b).White solid:60.1mg(89%); mp 178.4-181.1℃. 1 HNMR (600MHz, DMSO-d6) δ12.80 (s, 1H), 7.85–7.81 (m, 2H), 7.29 (d, J = 8.0Hz, 2H), 2.36 (s, 3H). 13C NMR(151MHz,DMSO-d6)δ167.3,143.0,129.3,129.1,128.0,21.1. 13 C NMR(151MHz,DMSO-d6)δ167.3,143.0,129.3,129.1,128.0,21.1.HRMS(m / z):[M-H] + Calcd.forC8H8O2135.0446;found 135.0443.

[0057]

[0058] 4-ethylbenzoic acid(4c).White solid:61.5mg(82%);mp 112.1-113.2℃. 1 HNMR(600MHz,DMSO-d6)δ12.80(s,1H),7.88–7.82(m,2H),7.33(d,J=8.0Hz,2H),2.67(q,J=7.6Hz,2H),1.19(t,J=7.6Hz,3H). 13 C NMR(151MHz,DMSO-d6)δ167.3,149.1,129.4,128.3,127.9,28.1,15.2.HRMS(m / z):[M-H] + Calcd.for C9H 10 O2149.0603;found 149.0606.

[0059]

[0060] 4-(tert-butyl)benzoic acid(4d).White solid:98.8mg(75%);mp 163.1-165.4℃. 1 H NMR(600MHz,DMSO-d6)δ12.79(s,1H),7.89–7.84(m,2H),7.53–7.49(m,2H),1.30(s,9H). 13 C NMR(151MHz,DMSO-d6)δ167.2,155.8,129.2,128.0,125.3,34.7,30.8.HRMS(m / z):[M-H] + Calcd.for C 11 H 14 O2177.0916;found 177.0933.

[0061]

[0062] 4-methoxybenzoic acid(4e).White solid:56.4mg(74%);mp 183.1-185.4℃. 1 H NMR(600 MHz,DMSO-d6)δ12.63(s,1H),7.91–7.86(m,2H),7.01(d,J=8.8 Hz,2H),3.82(s,3H). 13 C NMR(151MHz,DMSO-d6)δ167.0,162.8,131.3,123.0,113.8,55.4.HRMS(m / z):[M-H] + Calcd.for C8H8O3151.0395;found 151.0394.

[0063]

[0064] 2-methylbenzoic acid(4f).White solid:59.4mg(87%);mp 101.1-103.5℃. 1 HNMR(600 MHz,DMSO-d6)δ12.81(s,1H),7.81(d,J=7.8 Hz,1H),7.43(t,J=7.4 Hz,1H),7.28(dd,J=13.3,7.4 Hz,2H),2.51(s,3H). 13 C NMR(151 MHz,DMSO-d6)δ168.7,138.9,131.6,131.5,130.5,130.1,125.8,21.2.HRMS(m / z):[M-H] + Calcd.for C8H8O2135.0446;found 135.0452.

[0065]

[0066] 4-fluorobenzoic acid(4g).White solid:67.9mg(98%);mp 181.0-183.5℃. 1 HNMR(600 MHz,DMSO-d6)δ13.05(s,1H),8.10–7.90(m,2H),7.31(td,J=9.0,2.7 Hz,2H). 13CNMR(151 MHz,DMSO-d6)δ166.4,165.7,164.1,132.1,132.1,127.4,115.7,115.5.HRMS(m / z):[M-H] + Calcd.forC7H5O2F 139.0196;found 139.0202.

[0067]

[0068] 4-chlorobenzoic acid(4h).White solid:72.5mg(93%);mp 238.1-240.6℃. 1 HNMR(600 MHz,DMSO-d6)δ13.19(s,1H),7.94(d,J=8.6 Hz,2H),7.56(d,J=8.6 Hz,2H). 13 CNMR(151 MHz,DMSO-d6)δ166.5,137.8,131.1,129.7,128.7.HRMS(m / z):[M-H] + Calcd.forC7H5O2Cl 154.9900;found 154.9905.

[0069]

[0070] 4-bromobenzoic acid(4i).White solid:95.6mg(96%);mp 250.2-253.3℃. 1 HNMR(600 MHz,DMSO-d6)δ13.20(s,1H),7.88–7.83(m,2H),7.74–7.67(m,2H). 13 C NMR(151MHz,DMSO-d6)δ166.6,131.7,131.3,130.0,126.9.HRMS(m / z):[M-H] + Calcd.for C7H5O2Br198.9395;found121.0295.

[0071]

[0072] 3,4-difluorobenzoic acid(4j).White solid:64.9mg(83%);mp 121.4-123.5℃. 1H NMR(600 MHz,DMSO-d6)δ13.38(s,1H),7.89(t,J=9.5 Hz,1H),7.81(dd,J=4.5,2.3Hz,1H),7.56(q,J=9.5,8.5Hz,1H). 13 C NMR(151 MHz,DMSO-d6)δ165.5,153.3,153.3,151.7,151.6,150.1,150.0,148.5,148.4,128.5,126.9,126.9,118.5,118.4,117.9,117.8.HRMS(m / z):[M-H] + Calcd.for C7H4O2F2157.0101;found 157.0115.

[0073]

[0074] 2,4-dichlorobenzoic acid(4k).White solid:81.3mg(85%);mp 156.5-159.8℃. 1 H NMR(600 MHz,DMSO-d6)δ13.58(s,1H),7.82(d,J=8.4 Hz,1H),7.73(q,J=2.1 Hz,1H),7.52(dt,J=8.3,2.0 Hz,1H). 13 C NMR(151 MHz,DMSO-d6)δ165.8,136.5,133.0,132.3,130.2,130.1,127.5.HRMS(m / z):[M-H] + Calcd.for C7H4O2Cl2188.9510;found188.9529.

[0075]

[0076] 4-(trifluoromethyl)benzoic acid(4l).White solid:68.0mg(73%);mp218.4-221.2℃. 1 H NMR(600MHz,DMSO-d6)δ13.68–13.32(m,1H),8.13(d,J=8.0 Hz,2H),7.87(d,J=8.0 Hz,2H). 13C NMR(151 MHz,DMSO-d6)δ166.2,134.6,132.6,132.4,130.1,125.6,125.6,124.7,122.9.HRMS(m / z):[M-H] + Calcd.for C8H5O2F3189.0164;found189.0171.

[0077]

[0078] 2-fluoro-4-(trifluoromethyl)benzoic acid(4m).White solid:54.2mg(52%);mp 166.5-168.9℃. 1 HNMR(600 MHz,DMSO-d6)δ13.76(s,1H),8.06(t,J=7.7 Hz,1H),7.82(d,J=10.6 Hz,1H),7.69(d,J=6.5 Hz,1H). 13 C NMR(151 MHz,DMSO-d6)δ164.0,161.5,159.8,134.1,134.0,133.8,133.8,133.1,123.8,123.6,123.5,122.0,121.3,121.3,121.3,114.7,114.5,114.5.HRMS(m / z):[M-H] + Calcd.for C8H4O2F4207.0069;found207.0078.

[0079]

[0080] 4-hydroxybenzoic acid(4n).White solid:50.2mg(73%);mp 214.1-216.3℃. 1 H NMR(600 MHz,DMSO-d6)δ12.36(s,1H),10.29(s,1H),7.82–7.76(m,2H),6.85–6.79(m,2H). 13 C NMR(151MHz,DMSO-d6)δ167.6,162.1,132.0,121.9,115.6.HRMS(m / z):[M-H] + Calcd.for C7H6O3137.0239;found 137.0253.

[0081]

[0082] 3-nitrobenzoic acid(4o).White solid:53.4mg(64%);mp 138.4-139.6℃. 1 HNMR(600 MHz,DMSO-d6)δ13.71(s,1H),8.61(s,1H),8.46(s,1H),8.35(d,J=7.5 Hz,1H),7.85–7.76(m,1H). 13 CNMR(151 MHz,DMSO-d6)δ165.5,147.9,135.4,135.3,132.5,130.5,130.5,130.5,127.3,127.3,127.3,123.7.HRMS(m / z):[M-H] + Calcd.for C7H5NO4166.0141;found 166.0153.

[0083]

[0084] 4-(methylthio)benzoic acid(4p).White solid:100.4mg(81%);mp 193.2-195.8℃. 1 H NMR(600MHz,DMSO-d6)δ12.84(s,1H),7.85(d,J=8.3 Hz,2H),7.33(dd,J=8.5,2.0 Hz,2H),2.52(s,3H). 13 C NMR(151 MHz,DMSO-d6)δ167.0,144.8,129.7,126.7,124.9,13.9.HRMS(m / z):[M-H] + Calcd.for C8H8O2S 167.0167;found 167.0180.

[0085]

[0086] 4-aminobenzoic acid(4q).White solid:47.2mg(70%);mp 186.5-188.4℃. 1 HNMR(600 MHz,DMSO-d6)δ11.95(s,1H),7.61(t,J=8.4 Hz,2H),6.58–6.50(m,2H),5.87(s,2H). 13C NMR(151MHz,DMSO-d6)δ167.5,167.5,153.1,131.2,116.9,112.6.HRMS(m / z):[M-H] + Calcd.forC7H7NO2136.0399;found 136.0396.

[0087]

[0088] 2-naphthoic acid(4r).White solid:73.3mg(86%);mp 185.4-188.3℃. 1 H NMR(600 MHz,DMSO-d6)δ13.09(s,1H),8.61(s,1H),8.11(d,J=8.2 Hz,1H),8.00(q,J=8.7Hz,3H),7.63(dt,J=30.2,7.2 Hz,2H). 13 C NMR(151 MHz,DMSO-d6)δ167.4,134.9,132.1,130.5,129.3,128.3,128.1,128.1,127.6,126.8,125.1.HRMS(m / z):[M-H] + Calcd.forC 11 H8O2171.0446;found 171.0454.

[0089]

[0090] [1,1'-biphenyl]-4-carboxylic acid(4s).White solid:60.1mg(61%);mp221.1-224.9℃. 1 H NMR(600 MHz,DMSO-d6)δ13.26–12.74(m,1H),8.02(d,J=8.4 Hz,2H),7.77(dd,J=39.3,7.7 Hz,4H),7.46(dt,J=47.0,7.4 Hz,3H). 13 C NMR(151 MHz,DMSO-d6)δ167.1,144.3,139.0,129.9,129.7,129.1,128.3,126.9,126.8.HRMS(m / z):[M-H] + Calcd.for C 13 H 10O2197.0603;found197.0611.

[0091]

[0092] thiophene-2-carboxylic acid(4t).White solid:45.5mg(71%);mp 124.9-126.5℃. 1 H NMR(600MHz,DMSO-d6)δ13.06(s,1H),7.88(dd,J=4.3,2.4 Hz,1H),7.73(dd,J=3.7,1.3 Hz,1H),7.18(ddd,J=5.1,3.7,1.5 Hz,1H). 13 C NMR(151 MHz,DMSO-d6)δ162.9,134.7,133.2,133.2,128.2.HRMS(m / z):[M-H] + Calcd.for C5H4O2S 126.9854;found126.9863.

[0093]

[0094] Nicotinic acid(4u).White solid:58.4mg(66%);mp 236.4-238.5℃. 1 H NMR(600 MHz,DMSO-d6)δ13.43(s,1H),9.07(d,J=2.3 Hz,1H),8.78(dd,J=4.9,1.8 Hz,1H),8.26(dt,J=8.0,2.0 Hz,1H),7.54(dd,J=7.9,4.8 Hz,1H). 13 C NMR(151 MHz,DMSO-d6)δ166.3,153.3,150.2,137.0,126.6,123.8.HRMS(m / z):[M-H] + Calcd.for C6H5O2N122.0242;found 122.0242.

[0095]

[0096] Isobutyric acid(4v).Colorless liquid:23.2mg(53%). 1H NMR(600 MHz,DMSO-d6)δ12.01(s,1H),2.41(hept,J=6.9 Hz,1H),1.05(d,J=7.0 Hz,6H). 13 C NMR(151MHz,DMSO-d6)δ177.8,33.1,18.9.HRMS(m / z):[M-H] + Calcd.for C4H8O287.0446;found87.0455.

[0097]

[0098] Pentanoic acid(4w).Colorless liquid:41.3mg(82%). 1 H NMR(600 MHz,DMSO-d6)δ11.97(s,1H),2.19(t,J=7.4 Hz,2H),1.47(p,J=7.5 Hz,2H),1.28(h,J=7.4 Hz,2H),0.86(t,J=7.4 Hz,3H). 13 CNMR(151 MHz,DMSO-d6)δ174.5,33.4,26.6,21.7,13.6.HRMS(m / z):[M-H] + Calcd.for C5H 10 O2101.0603;found 101.0605.

[0099]

[0100] Hexanoic acid(4x).Colorless liquid:45.0mg(78%). 1 H NMR(600 MHz,DMSO-d6)δ11.96(s,1H),2.18(t,J=7.4 Hz,2H),1.49(p,J=7.4 Hz,2H),1.31–1.19(m,4H),0.85(t,J=7.0 Hz,3H). 13 CNMR(151 MHz,DMSO-d6)δ174.5,33.7,30.8,24.2,21.9,13.8.HRMS(m / z):[M-H] + Calcd.forC6H 12 O2115.0759;found 115.0768.

[0101]

[0102] 3-methylpentanoic acid(4y).Colorless liquid:43.7mg(76%). 1 H NMR(600MHz,Chloroform-d)δ2.35(dd,J=14.9,6.0 Hz,1H),2.18–2.09(m,1H),1.89(h,J=7.0,6.6 Hz,1H),1.39(tt,J=13.2,7.5Hz,1H),1.29–1.20(m,1H),0.96(d,J=6.6 Hz,3H),0.90(t,J=7.5 Hz,3H). 13 C NMR(151 MHz,Chloroform-d)δ180.0,41.3,31.9,29.4,19.4,11.4.HRMS(m / z):[M-H] + Calcd.for C5H 10 O2115.0759;found 115.0754.

[0103]

[0104] 4-chlorobutanoic acid(4z).Colorless liquid:47.2mg(78%). 1 H NMR(600MHz,DMSO-d6)δ12.20(s,1H),3.65(t,J=6.5 Hz,2H),2.36(t,J=7.3 Hz,2H),1.93(p,J=6.9 Hz,2H). 13 C NMR(151 MHz,DMSO-d6)δ173.6,44.6,30.8,27.6.HRMS(m / z):[M-H] + Calcd.for C4H7O2Cl 121.0057;found121.0087.

[0105]

[0106] Cyclopentanecarboxylic acid(4aa).Colorless liquid:36.4mg(65%);mp121.4-122.8℃. 1H NMR(600 MHz,DMSO-d6)δ11.95(s,1H),2.63(p,J=7.9 Hz,1H),1.78(td,J=12.4,8.1 Hz,2H),1.70–1.63(m,2H),1.62–1.55(m,2H),1.54–1.46(m,2H). 13 C NMR(151 MHz,DMSO-d6)δ177.3,43.2,29.4,25.4.HRMS(m / z):[M-H] + Calcd.forC6H 10 O2113.0603;found 113.0596.

[0107]

[0108] Cyclohexanecarboxylic acid(4ab).Colorless liquid:36.2mg(57%). 1 H NMR(600 MHz,DMSO-d6)δ11.97(s,1H),2.18(tt,J=10.9,3.7 Hz,1H),1.79(d,J=13.0 Hz,2H),1.69–1.61(m,2H),1.57(d,J=12.5 Hz,1H),1.37–1.09(m,5H). 13 C NMR(151 MHz,DMSO-d6)δ176.7,42.2,28.6,25.4,24.9.HRMS(m / z):[M-H] + Calcd.for C7H 12 O2127.0759;found 127.0862.

[0109]

[0110] 2-cyclohexylacetic acid(4ac).Colorless liquid:29.1mg(41%). 1 H NMR(600MHz,DMSO-d6)δ11.97(s,1H),2.07(d,J=6.8 Hz,2H),1.70–1.55(m,6H),1.26–1.05(m,3H),0.91(qd,J=13.8,12.8,4.0 Hz,2H). 13C NMR(151 MHz,DMSO-d6)δ173.7,41.5,34.2,32.4,25.7,25.6.HRMS(m / z):[M-H] + Calcd.for C8H 14 O2141.0916;found 141.0924.

[0111]

[0112] 2-phenylacetic acid(4ad).White solid:68.7mg(70%);mp 108.4-111.1℃. 1 HNMR(600 MHz,DMSO-d6)δ12.33(s,1H),7.31(t,J=7.5 Hz,2H),7.24(dd,J=12.7,7.2 Hz,3H),3.56(s,2H). 13 CNMR(151 MHz,DMSO-d6)δ172.7,135.0,129.4,128.2,126.6,40.7.HRMS(m / z):[M-H] + Calcd.for C8H8O2135.0446;found 135.0456.

[0113]

[0114] (Z)-6-(2-oxo-1-phenylindolin-3-ylidene)hexanoic acid(6a).Yellow oil:90.4mg(57%);z / e=1 / 1.76;mp 121.4-122.8℃. 1 H NMR(600 MHz,Chloroform-d)δ7.52(t,J=7.8 Hz,2H),7.46(d,J=7.5 Hz,1H),7.45–7.36(m,3H),7.18(t,J=7.7 Hz,1H),7.05(t,J=7.6 Hz,1H),6.97(t,J=7.9 Hz,1H),6.81(d,J=7.8 Hz,1H),3.07(q,J=7.6Hz,2H),2.42(t,J=7.4 Hz,2H),1.77(p,J=7.3 Hz,2H),1.66(p,J=7.5 Hz,2H). 13C NMR(151 MHz,Chloroform-d)δ179.1,166.8,142.8,142.1,134.7,129.6,128.7,128.0,127.3,126.8,123.1,122.5,119.3,109.4,33.8,28.6,27.5,24.5.HRMS(m / z):[M-H] + Calcd.forC 20 H 19 O3N 320.1287;found 320.1300.

[0115]

[0116] (E)-6-(2-oxo-1-phenylindolin-3-ylidene)hexanoic acid(6a).Yellow oil:90.4mg(57%);z / e=1 / 1.76. 1 H NMR(600 MHz,Chloroform-d)δ7.61(d,J=7.6 Hz,1H),7.52(t,J=7.8 Hz,2H),7.40(dd,J=11.3,7.6 Hz,3H),7.20(t,J=7.8 Hz,1H),7.13(t,J=7.6 Hz,1H),7.08(t,J=7.6 Hz,1H),6.83(d,J=7.9 Hz,1H),2.77(q,J=7.4 Hz,2H),2.44(t,J=7.2 Hz,2H),1.82(dt,J=14.4,7.1 Hz,2H),1.79–1.72(m,2H). 13 C NMR(151MHz,Chloroform-d)δ178.6,167.4,143.7,142.3,134.7,129.7,128.9,128.1,127.9,126.9,123.8,122.7,122.3,109.6,33.8,29.2,28.1,24.6.HRMS(m / z):[M-H] + Calcd.forC 20 H 19 O3N 320.1287;found 320.1300.

[0117]

[0118] (E)-6-(2-oxo-1-phenylindolin-3-ylidene)heptanoic acid(6b).Yellow oil:100.3mg(60%);z / e=1 / 9.53. 1 H NMR(600 MHz,Chloroform-d)δ7.60(d,J=7.7 Hz,1H),7.52(t,J=7.7 Hz,2H),7.43–7.39(m,3H),7.18(t,J=7.6 Hz,1H),7.08(t,J=7.6 Hz,1H),6.80(d,J=7.8 Hz,1H),3.18–3.10(m,2H),2.43(d,J=4.3 Hz,3H),2.41(d,J=7.5Hz,2H),1.76(q,J=7.5 Hz,2H),1.65(dd,J=15.3,7.0 Hz,2H). 13 C NMR(151 MHz,Chloroform-d)δ179.5,167.0,159.8,142.2,134.8,129.6,128.0,127.7,127.3,123.9,123.8,122.7,122.3,109.0,35.6,33.9,27.6,24.8,23.9.HRMS(m / z):[M-H] + Calcd.forC 21 H 21 O3N 334.1443;found 334.1453.

[0119]

[0120] (E)-4-methyl-6-(2-oxo-1-phenylindolin-3-ylidene)hexanoic acid(6c).Yellow oil:94.4mg(57%);z / e=1 / 1.42. 1H NMR(600 MHz,Chloroform-d)δ7.65–7.60(m,1H),7.54–7.49(m,2H),7.41(dd,J=13.5,7.4 Hz,3H),7.20(t,J=7.7 Hz,1H),7.16(t,J=7.6 Hz,1H),7.08(t,J=7.6 Hz,1H),6.83(d,J=8.2 Hz,1H),2.78–2.72(m,1H),2.63(dt,J=15.7,7.7 Hz,1H),2.52–2.38(m,2H),1.96–1.83(m,2H),1.65(td,J=14.2,8.5 Hz,1H),1.08(d,J=6.6 Hz,3H). 13 C NMR(151 MHz,Chloroform-d)δ178.6,167.3,143.7,141.3,134.8,129.7,129.0,128.4,128.1,126.9,123.8,122.7,122.4,109.6,36.6,33.1,31.8,31.7,19.6.HRMS(m / z):[M-H] + Calcd.for C 21 H 21 O3N 334.1443;found334.1459.

[0121]

[0122] (E)-3,3-dimethyl-6-(2-oxo-1-phenylindolin-3-ylidene)hexanoic acid(6d).Yellow solid:82.9mg(48%);z / e=1 / 1.54;mp 184.1-186.2℃. 1 H NMR(600 MHz,Chloroform-d)δ7.63(d,J=7.5 Hz,1H),7.52(t,J=7.8 Hz,2H),7.40(dd,J=12.4,7.3Hz,3H),7.20(t,J=7.2 Hz,1H),7.13(t,J=7.7 Hz,1H),7.09(t,J=7.5 Hz,1H),6.83(d,J=7.9 Hz,1H),2.78–2.71(m,2H),2.35(s,2H),1.77–1.69(m,2H),1.16(s,6H). 13C NMR(151 MHz,Chloroform-d)δ177.6,167.4,143.6,143.0,134.8,129.7,128.9,128.1,127.4,126.9,123.7,122.7,122.3,109.6,45.7,40.4,33.4,27.4,24.7.HRMS(m / z):[M-H] + Calcd.for C 22 H 23 O3N 348.1600;found 348.1610.

[0123]

[0124] (E)-2-cyclohexyl-6-(2-oxo-1-phenylindolin-3-ylidene)hexanoic acid(6e).Red solid:101.9mg(51%);z / e=1 / 2.7;mp 147.4-150.8℃. 1 H NMR(600 MHz,Chloroform-d)δ7.61(d,J=7.5 Hz,1H),7.51(t,J=7.8 Hz,2H),7.40(dd,J=12.6,7.6Hz,3H),7.20(t,J=7.7 Hz,1H),7.12(t,J=7.6 Hz,1H),7.08(t,J=7.6 Hz,1H),6.83(d,J=7.9 Hz,1H),2.76(q,J=7.2 Hz,2H),2.28–2.21(m,1H),1.80–1.55(m,10H),1.24(qd,J=12.8,3.6 Hz,2H),1.18–1.05(m,2H),1.05–0.96(m,1H). 13 C NMR(151MHz,Chloroform-d)δ181.2,167.4,143.7,142.4,134.8,129.7,128.9,128.0,127.8,126.9,123.8,122.7,122.4,109.6,51.7,40.2,31.1,30.6,29.5,29.0,26.9,26.4.HRMS(m / z):[M-H] + Calcd.forC 26 H 29 O3N 402.2069;found 402.2079.

[0125]

[0126] (E)-6-(2-oxo-1-phenylindolin-3-ylidene)-2-phenylhexanoic acid(6f).Yellow solid:123.9mg(63%);z / e=1 / 1.73;mp 179.4-182.6℃. 1 H NMR(600 MHz,Chloroform-d)δ7.54(d,J=7.6 Hz,1H),7.52–7.49(m,2H),7.42–7.38(m,3H),7.33(d,J=3.8 Hz,4H),7.29–7.27(m,1H),7.19(t,J=7.8 Hz,1H),7.07(q,J=8.7,8.2 Hz,2H),6.81(d,J=7.9 Hz,1H),3.61(t,J=7.7 Hz,1H),2.73(dt,J=15.2,7.8 Hz,2H),2.27–2.19(m,1H),2.01–1.91(m,1H),1.75–1.67(m,1H),1.66–1.58(m,1H). 13 CNMR(151 MHz,Chloroform-d)δ178.7,167.3,143.7,142.1,138.3,134.7,129.7,129.0,128.9,128.2,128.1,127.9,127.8,126.9,123.8,122.7,122.3,109.6,51.4,33.0,29.3,26.7.HRMS(m / z):[M-H] + Calcd.for C 26 H 23 O3N 396.1600;found 396.1602.

[0127]

[0128] (E)-5-(2-oxo-1-phenylindolin-3-ylidene)pentanoic acid(6g).Yellowsolid:82.2mg(54%);z / e=1 / 1.80;mp 143.4-146.2℃. 1H NMR(400 MHz,Chloroform-d)δ7.63(d,J=7.8 Hz,1H),7.55–7.50(m,2H),7.41(d,J=7.9 Hz,3H),7.23–7.18(m,1H),7.09(dt,J=10.9,7.6 Hz,2H),6.83(dt,J=7.8,0.8Hz,1H),2.82(q,J=7.6 Hz,2H),2.53(t,J=7.2 Hz,2H),2.03(p,J=7.4 Hz,2H). 13 C NMR(151MHz,Chloroform-d)δ178.3,167.3,143.8,141.2,134.7,129.7,129.1,128.4,128.1,126.9,123.9,122.8,122.2,109.6,33.4,28.7,23.7.HRMS(m / z):[M-H] + Calcd.for C 19 H 17 O3N 306.1130;found306.1134.

[0129]

[0130] (E)-5-(2-oxo-1-phenylindolin-3-ylidene)hexanoic acid(6h).Yellowsolid:92.3mg(58%);z / e=0 / 1;mp 174.1-176.8℃. 1 H NMR(600 MHz,Chloroform-d)δ7.60(d,J=7.7 Hz,1H),7.54–7.49(m,2H),7.43–7.37(m,3H),7.18(t,J=7.1 Hz,1H),7.08(t,J=7.1 Hz,1H),6.80(d,J=7.8 Hz,1H),3.20–3.15(m,2H),2.46(t,J=7.4 Hz,2H),2.44(s,3H),1.93(p,J=7.5 Hz,2H). 13 C NMR(151MHz,Chloroform-d)δ178.9,167.0,158.7,142.3,134.8,129.7,128.0,127.9,127.3,124.0,123.7,123.2,122.4,109.1,35.1,33.7,23.8,23.2.HRMS(m / z):[M-H]+ Calcd.for C 20 H 19 O3N 320.1287;found 320.1298.

[0131]

[0132] (Z)-5-(2-oxo-1-phenylindolin-3-ylidene)undecanoic acid(6i).Yellowoil:93.3mg(48%);z / e=1 / 1.61. 1 H NMR(600 MHz,Chloroform-d)δ7.62(d,J=7.8 Hz,1H),7.52(t,J=7.7 Hz,2H),7.40(dd,J=12.6,7.6 Hz,3H),7.16(t,J=7.6 Hz,1H),7.07(t,J=7.6 Hz,1H),6.79(d,J=7.8 Hz,1H),3.07–3.00(m,2H),2.82–2.75(m,2H),2.59(t,J=7.1 Hz,2H),2.02(dt,J=15.2,7.1 Hz,2H),1.56(p,J=8.0,7.4 Hz,2H),1.43(t,J=7.4 Hz,2H),1.32–1.28(m,4H),0.87(t,J=6.8 Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ178.7,167.1,163.6,142.4,134.9,129.7,128.0,127.9,127.3,123.5,122.9,122.5,122.4,109.2,35.7,34.9,34.0,31.9,30.1,28.8,22.8,22.2,14.2.HRMS(m / z):[M-H] + Calcd.for C 25 H 29 O3N 390.2069;found 390.2076.

[0133]

[0134] (E)-5-(2-oxo-1-phenylindolin-3-ylidene)undecanoic acid(6i).Yellowoil:93.3mg(48%);z / e=1 / 1.61. 1H NMR(600 MHz,Chloroform-d)δ7.54–7.49(m,3H),7.40(d,J=7.6 Hz,3H),7.17(t,J=7.7 Hz,1H),7.08(t,J=7.7 Hz,1H),6.79(d,J=7.8Hz,1H),3.11–3.05(m,2H),2.74–2.66(m,2H),2.48(t,J=7.4 Hz,2H),1.96–1.86(m,2H),1.71–1.63(m,2H),1.52(t,J=7.5 Hz,2H),1.37(q,J=3.6 Hz,4H),0.95–0.91(m,3H). 13 CNMR(151 MHz,Chloroform-d)δ178.8,167.2,164.0,142.4,134.9,129.7,128.0,127.9,127.3,123.6,122.9,122.5,122.5,109.2,36.7,34.0,33.9,31.8,30.0,27.3,23.6,22.7,14.2.HRMS(m / z):[M-H] + Calcd.for C 25 H 29 O3N 390.2069;found 390.2073.

[0135]

[0136] (E)-7-(2-oxo-1-phenylindolin-3-ylidene)heptanoic acid(6j).Yellowsolid:99.6mg(60%);z / e=1 / 1.60;mp 82.5-84.5℃. 1 H NMR(600 MHz,Chloroform-d)δ7.61(d,J=7.6 Hz,1H),7.52(t,J=7.8 Hz,2H),7.40(dd,J=12.9,7.5 Hz,3H),7.20(t,J=7.7 Hz,1H),7.14(t,J=7.6 Hz,1H),7.08(t,J=7.6Hz,1H),6.83(d,J=7.9 Hz,1H),2.75(q,J=7.5 Hz,2H),2.39(t,J=7.4 Hz,2H),1.72(p,J=7.6 Hz,4H),1.53(q,J=8.0Hz,2H). 13C NMR(151 MHz,Chloroform-d)δ179.0,167.4,143.6,142.8,134.8,129.7,128.9,128.1,127.7,126.9,123.8,122.7,122.4,109.6,33.9,29.4,29.0,28.4,24.6.HRMS(m / z):[M-H] + Calcd.for C 21 H 21 O3N 334.1443;found 334.1452.

[0137]

[0138] (E)-2-(3-(2-oxo-1-phenylindolin-3-ylidene)propyl)benzoic acid(6k).White solid:77.0mg(42%);z / e=1 / 1.56;mp 192.5-194.1℃. 1 H NMR(600 MHz,Chloroform-d)δ8.09(d,J=7.9 Hz,1H),7.61(d,J=7.6 Hz,1H),7.52(q,J=8.2 Hz,3H),7.43–7.36(m,4H),7.34(t,J=7.6 Hz,1H),7.24(t,J=8.1 Hz,1H),7.16(t,J=7.7 Hz,1H),7.04(t,J=7.6 Hz,1H),6.81(d,J=7.9 Hz,1H),3.39(t,J=7.8Hz,2H),3.11(q,J=7.8 Hz,2H). 13 C NMR(151 MHz,Chloroform-d)δ171.7,167.5,143.8,143.6,142.1,134.8,133.4,132.2,131.5,129.7,128.8,128.3,128.0,127.8,126.9,126.8,123.9,122.7,122.3,109.5,33.8,31.5.HRMS(m / z):[M-H] + Calcd.for C 24 H 19 O3N 368.1287;found368.1297.

[0139]

[0140] (E)-2-(4-(2-oxo-1-phenylindolin-3-ylidene)butyl)benzoic acid(6l).White solid:81.8mg(43%);z / e=1 / 1.66;mp 156.4-159.8℃. 1 H NMR(600MHz,Chloroform-d)δ8.08(d,J=8.0Hz,1H),7.54(d,J=7.6Hz,1H),7.50(d,J=7.7Hz,3H),7.43–7.38(m,3H),7.34–7.29(m,2H),7.23(t,J=7.7Hz,1H),7.17(t,J=7.6Hz,1H),7.05(t,J=7.6Hz,1H),6.81(d,J=7.9Hz,1H),3.20(dd,J=9.0,6.5Hz,2H),2.81(q,J=7.6Hz,2H),2.08–1.99(m,2H). 13 C NMR(151MHz,Chloroform-d)δ172.3,167.5,144.7,143.6,142.9,134.8,133.1,132.1,131.5,129.7,128.8,128.4,128.0,127.8,126.9,126.4,123.8,122.7,122.4,109.5,34.4,30.6,29.4.HRMS(m / z):[M-H] + Calcd.forC 25 H 21 O3N382.1443;found 382.1452.

[0141]

[0142] 3-((3S,3aS,5aS,6R,7S,9aR,9bS)-3-acetyl-3a,6-dimethyl-7-(((E)-2-oxo-1-phenylindolin-3-ylidene)methyl)dodecahydro-1H-cyclopenta[a]naphthalen-6-yl)propanoic acid(6n).White solid:112.0mg(40%);z / e=1 / 1.23;mp 121.4-122.8℃. 1HNMR(600MHz,Chloroform-d)δ7.62(d,J=7.5Hz,1H),7.52(t,J=7.8Hz,2H),7.41(dd,J=14.7,7.5Hz,3H),7.24(d,J=7.0Hz,1H) ,7.19(t,J=7.6Hz,1H),7.08(t,J=7.6Hz,1H),6.81(d,J=7.8Hz,1H),2.86(dd,J=18.6,7.3Hz,1H),2.68(dd,J=18.6,6.8Hz,1H), 2.51(t,J=9.0Hz,1H),2.45(dd,J=15.1,3.1Hz,1H),2.18–2.09(m,2H),2.08(s,3H),2.04(d,J=6.0Hz,1H),2.02–1.99(m,1H),1. 93(dd,J=8.4,2.6Hz,1H),1.75–1.63(m,4H),1.45–1.27(m,6H),1.05–0.97(m,1H),0.94(s,3H),0.90–0.86(m,1H),0.60(s,3H). 13 C NMR(151MHz,Chloroform-d)δ209.8,178.3,167.1,143.8,138.1,134.7,129.7,129.0,128.5,128.1,127.0,123.8,122.8,122.3, 109.6,63.8,56.5,48.1,44.0,39.9,39.6,38.9,36.7,35.9,35.4,31.6,31.3,27.9,24.5,23.0,21.8,16.1,13.4.HRMS(m / z):[MH] + Calcd.forC 35 H 41 O4N538.2958; found538.2966.

[0143] The above description represents the preferred embodiments of the present invention. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principles of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for an N-phenylindigo-mediated ketone-carboxylic acid conversion reaction, characterized in that, N-phenylindigo and ketone organic compounds are mixed, a catalyst and a solvent are added, and the mixture is reacted at 80-100℃ for 12-24 hours. After quenching the reaction, the organic layer is dried and the solvent is removed by rotary evaporation. The residue is purified by chromatography to obtain carboxylic acid organic compounds. The catalyst is one of trifluoromethanesulfonic acid, trifluoroacetic acid, and p-toluenesulfonic acid; The solvent is one of cyclohexane, chloroform, 1,4-dioxane, n-heptane, and dodecane; Ketones are one of the following organic compounds: phenylbutanone, 4-methylphenylacetone, 4-ethylphenylacetone, 4-methoxyphenylacetone, 4-benzyloxyphenylacetone, 3-chlorophenylacetone, 4-chlorophenylacetone, 4-trifluoromethylphenylacetone, 4-fluorophenylacetone, 4-hydroxyphenylacetone, 3-nitrophenylacetone, 4-aminophenylacetone, 3-pyridylethyl ketone, 1-(naphthyl-2-yl)prop-1-one, 1-cyclopentyl-prop-1-one, 5-methyl-3-heptanone, 1-tetrahydronaphthone, 2-phenylcyclohexanone, cyclohexanone, cyclopentanone, and cycloheptanone.

2. The method for N-phenylindochrome-mediated ketone-carboxylic acid conversion reaction according to claim 1, characterized in that, The molar ratio of N-phenylindigo to ketone organic compounds is 1:1.2-1.

5.

3. The method for N-phenylindigo-mediated ketone-carboxylic acid conversion reaction according to claim 1, characterized in that, The molar ratio of the catalyst to N-phenylindigo is 0.8-5.

4. The method for N-phenylindochrome-mediated ketone-carboxylic acid conversion reaction according to claim 1, characterized in that, The reaction was carried out at 80℃ for 16 hours.

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