3-indole-o-carborane methanol derivatives and green synthesis method thereof

Abstract

This invention discloses a 3-indole-o-carborane methanol derivative and its green synthesis method. The method involves using 1-aldehyde-o-carborane as a starting material, without the need for catalysts or solvents, and synthesizing the 3-indole-o-carborane methanol derivative efficiently through a nucleophilic addition reaction of the C3-H group of indole to the aldehyde group in air. This method has advantages such as simple operation, high yield, and wide substrate applicability. The preparation method of the 3-indole-o-carborane methanol derivative designed in this invention is simple to operate, requiring only the addition of 1-aldehyde-o-carborane and indole to a container. No solvent or metal catalyst is needed during the reaction, resulting in high yield and no additional waste generated, making it environmentally friendly. This invention provides a green, economical, and efficient method for the selective functionalization of o-carboranes, lays a technical foundation for the further design and synthesis of o-carborane-heterocyclic derivatives, and provides new ideas for the synthesis of mono-indole methanol compounds.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis and chemical synthesis technology, and relates to a 3-indole-o-carborane methanol derivative and its green synthesis method. Background Technology

[0002] o-Carboranes are a class of clusters composed of carbon, boron, and hydrogen, exhibiting an icosahedral structure. Their substituent effects are transmitted through a three-dimensional cage-like surface, readily undergoing electrophilic substitution reactions, and sharing some similarities with two-dimensional aromatic benzene rings. Since their discovery in the 1960s, o-carboranes and their derivatives have attracted increasing attention due to their unique photoelectric and biochemical properties, showing great promise for applications in the rubber industry, nonlinear optical devices, supramolecular chemistry, coordination chemistry, and medicinal chemistry. Therefore, research on the synthetic methodologies of o-carborane derivatives is of great significance for promoting the development of carborane chemistry and related materials science.

[0003] As the most widely distributed heterocyclic compound in nature, indole and its derivatives are extensively used in medicine, pesticides, and functional materials. Their unique and diverse structures have also inspired the development of modern synthetic methods, including the construction of the indole skeleton and the functionalization of the indole ring. Research results indicate that introducing different modifying groups into the indole structure holds promise for further enhancing the compound's biological activity and uncovering several potential properties and applications.

[0004] Indole can undergo nucleophilic addition reactions with aromatic aldehydes under Lewis acid catalysis to synthesize indole-modified aromatic alcohol skeletons. However, for aromatic aldehydes, the reaction products are mostly bisindolemethane compounds. The selective single addition reaction between indole and aromatic aldehydes requires strongly basic conditions. O-carborane molecules are acid-resistant but not base-resistant, and are easily deboronized or even degraded under basic conditions. Therefore, achieving the selective single addition reaction between o-carborane and indole is a challenging task, and existing research has not been able to obtain 3-indole-o-carborane methanol derivatives. Summary of the Invention

[0005] Based on existing research on the selective functionalization of o-carboranes and the promising applications of o-carborane derivatives in medicine and materials, the present invention aims to provide a simple, mild, widely applicable, green and efficient method for preparing 3-indole-o-carborane methanol derivatives.

[0006] Building upon previous research on the selective functionalization of o-carboranes, this invention proposes that 1-aldehyde-o-carboranes with three-dimensional aromaticity may undergo nucleophilic addition reactions with the 3-CH bond of indole. Simultaneously, by utilizing the steric hindrance and electronic effects of 1-aldehyde-o-carboranes, it is hoped that a selective single nucleophilic addition reaction can be achieved between 1-aldehyde-o-carboranes and the 3-CH bond of indole, thereby obtaining 3-indole-o-carborane methanol derivatives that were previously unattainable.

[0007] This invention utilizes the steric and electronic effects of 1-aldehyde-o-carborane to achieve a selective single addition reaction with the 3-CH bond of indole under solvent-free and catalyst-free conditions, thereby obtaining a 3-indole-o-carborane methanol derivative that could not be obtained in previous studies.

[0008] One object of the present invention is to solve at least the above-mentioned problems and / or defects, and to provide at least the advantages described below.

[0009] To achieve these objectives and other advantages of the present invention, a 3-indole-o-carborane methanol derivative with the following general structural formula is provided:

[0010]

[0011] Wherein, R1 is any one of alkyl, alkoxy, or halogen; R2 is any one of methyl, n-butyl, benzyl, phenyl, or hydrogen; and R3 is any one of methyl, phenyl, or substituted phenyl.

[0012] This invention also provides a green synthesis method for the 3-indole-o-carborane methanol derivative as described above, comprising:

[0013] by Using raw materials, under air atmosphere and a certain temperature, through C3-H The nucleophilic addition reaction of the aldehyde group efficiently synthesized a 3-indole-o-carborane methanol derivative; wherein R1 is any one of alkyl, alkoxy, or halogen; R2 is any one of methyl, n-butyl, benzyl, phenyl, or hydrogen; and R3 is any one of methyl, phenyl, or substituted phenyl.

[0014] The reaction formula for the green synthesis method is:

[0015]

[0016] Preferably, the specified temperature is 25–60°C.

[0017] Preferably, the The preparation method includes the following steps:

[0018] Step 1: Add to a dry reaction vessel Under argon protection, dry diethyl ether was added as a solvent, and the reaction system was placed at -78°C. N-butyllithium was slowly added dropwise using a dry syringe. After the system reacted at -78°C for 1 hour, methyl formate was added, and the reaction continued at -78°C for 2 hours. The reaction progress was monitored by TLC plate.

[0019] Step 2: After the reaction is complete and the system is brought to room temperature, hydrochloric acid is added to quench the reaction. Then, the reaction is extracted with ethyl acetate. The organic phase is washed three times with saturated NaHCO3 solution and saturated NaCl aqueous solution, respectively. The organic phase is collected and dried with anhydrous sodium sulfate.

[0020] Step 3: Remove the organic solvent by vacuum distillation, using petroleum ether and ethyl acetate as eluents, and separate by column chromatography to obtain a white solid, which is...

[0021] The reaction formula for the above preparation method is as follows:

[0022]

[0023] Preferably, the In this context, R3 can be any one of methyl, phenyl, or substituted phenyl.

[0024] The present invention has at least the following beneficial effects:

[0025] (1) The preparation method of the 3-indole-o-carborane methanol derivative designed in this invention is simple to operate. It only requires adding 1-aldehyde-o-carborane and indole to the container. No solvent or metal catalyst is needed during the reaction. The reaction yield is high and no additional waste is generated during the reaction. It is green and environmentally friendly.

[0026] (2) This invention provides a green, economical and efficient method for the selective functionalization of o-carboranes, lays a technical foundation for the further design of o-carborane-heterocyclic derivatives, and provides new ideas for the synthesis of monoindole methanol compounds.

[0027] Other advantages, objectives and features of the present invention will become apparent in part from the following description, and in part from those skilled in the art through study and practice of the invention. Attached image description:

[0028] Figure 1 As in embodiment 1 of the present invention, 3a 1 HNMR;

[0029] Figure 2 As in embodiment 1 of the present invention, 3a 13 CNMR;

[0030] Figure 3 As shown in embodiment 2 of the present invention, 3b 1 HNMR;

[0031] Figure 4 As shown in embodiment 2 of the present invention, 3b 13 CNMR;

[0032] Figure 5 As in embodiment 3c of the present invention 1 HNMR;

[0033] Figure 6 As in embodiment 3c of the present invention 13 CNMR;

[0034] Figure 7 3g in Example 7 of this invention 1 HNMR;

[0035] Figure 8 3g in Example 7 of this invention 13 CNMR;

[0036] Figure 9 For example, 5a in embodiment 11 of the present invention 1 HNMR;

[0037] Figure 10 For example, 5a in embodiment 11 of the present invention 13 CNMR. Detailed implementation method:

[0038] The present invention will now be described in further detail with reference to the accompanying drawings, so that those skilled in the art can implement it based on the description.

[0039] It should be understood that terms such as “having,” “comprising,” and “including” as used herein do not imply the presence or addition of one or more other elements or combinations thereof.

[0040] Example 1:

[0041] Phase 1: Preparation of 1-aldehyde-o-carborane

[0042]

[0043] Under an argon atmosphere, 30 mL of dry diethyl ether and 1.44 g of o-carborane (10 mmol) were added sequentially to a dry 100 mL round-bottom flask. The reaction flask was immersed in a -78 °C condenser bath and stirring was started. After the system temperature dropped to -78 °C, 6.9 mL of n-butyllithium (1.6 M, 12 mmol) was slowly added using a syringe. The system was reacted at -78 °C for 1 h, then 2 mL of methyl formate was added, and the reaction was continued at -78 °C for another 2 h. The reaction progress was monitored using TLC. After the reaction was completed, 3 mL (excess) of 3 M hydrochloric acid was slowly added to quench the reaction, and the system gradually became clear. The reaction was then extracted with ethyl acetate and washed sequentially with saturated NaHCO3 solution and saturated NaCl aqueous solution. The organic phase was collected and dried with anhydrous sodium sulfate. After drying for one hour, the organic phase was concentrated and separated by column chromatography using petroleum ether as the eluent to obtain 1.3 g of the target product, with a yield of 76%.

[0044] Phase 2: Optimization of conditions for the preparation of 3-indole-o-carborane methanol:

[0045] Taking the preparation of 3-indole-o-carborane methanol (3a) from 1-aldehyde-o-carborane (1a) as an example, the reaction conditions were optimized as follows (Table 1):

[0046]

[0047] Table 1

[0048]

[0049] After screening, the optimal conditions for synthesizing 3a were found to be number 11: reaction at room temperature in the absence of solvent and metal catalyst for 4 hours. Typical operating steps are as follows:

[0050] Preparation of 3a:

[0051]

[0052] Under air, 1-aldehyde-o-carborane 1a (17.2 mg, 0.1 mmol) and N-methylindole 2a (15.7 mg, 0.12 mmol) were added sequentially to a dry 10 mL test tube. The test tube was placed in an oil bath at 25 °C for reaction, and the reaction was monitored by TLC. After the reaction was completed, the product was purified by column chromatography using petroleum ether / ethyl acetate = 20:1 as the eluent. The product 3a was obtained by column chromatography with a yield of 30.0 mg, which was 99%.

[0053] NMR data: 1H NMR (400MHz, CDCl3, ppm): δ7.69-7.67(d,1H,J=8Hz),7.34-7.33(d,1H,J=8Hz),7.29-7.28( m,1H),7.19-7.16(m,1H),7.10(s,1H),5.63(s,1H),3.83(s,1H),3.81(s,3H),2.53(s,1H); 13 C{ 1 H}NMR (100MHz, CDCl3, ppm): δ136.8,127.6,125.6,122.6,120.4,119.6,113.1,109.8,79.9,70.6,59.8,33.1; 11 B{ 1 H}NMR(160MHz,CDCl3,ppm):-3.3(2B),-4.7(1B),-8.9(1B),-9.3(1B),-10.8(1B),-12.2(1B),-12.7(1B),-13.3(1B),-13.9(1B).HRMS(ESI)m / z calculated for C 12 H 20 B 10 NO - (MH) - 302.25536, found 302.25583.

[0054] Example 2:

[0055] Preparation of 3b:

[0056]

[0057] Under air, 1-aldehyde-o-carborane 1a (17.2 mg, 0.1 mmol) and 5-chloro-1-methylindole 2b (19.9 mg, 0.12 mmol) were added sequentially to a dry 10 mL test tube. The test tube was placed in an oil bath at 60 °C for reaction, and the reaction was monitored by TLC. After the reaction was completed, the product was purified by column chromatography using petroleum ether / ethyl acetate = 20:1 as the eluent. The product 3b was obtained by column chromatography at a yield of 31.7 mg, which was 94%.

[0058] NMR data: 1 H NMR (400MHz, CDCl3, ppm): δ7.64(m,1H),7.23(s,1H)7.22(m,1H),7.09(s,1H),5.55(s,1H),3.87(s,1H),3.79(s,3H),2.61(s,1H);13 C{ 1 H}NMR (100MHz, CDCl3, ppm): δ135.2,128.8,126.6,126.3,123.0,119.2,112.8,110.9,79.5,70.3,59.6,33.3; 11 B{ 1 H}NMR(160MHz,CDCl3,ppm):-3.3(2B),-4.6(1B),-8.8(1B),-9.3(1B),-11.0(1B),-12.4(1B),-13.2(1B),-13.9(2B).HRMS(ESI)m / z calculated for C 12 H 19 B 10 NOCl - (MH) - 336.2164, found 336.2150.

[0059] Example 3:

[0060] Preparation of 3C:

[0061]

[0062] Under air, 1-aldehyde-o-carborane 1a (17.2 mg, 0.1 mmol) and 5-chloro-1-methylindole 2c (19.3 mg, 0.12 mmol) were added sequentially to a dry 10 mL test tube. The test tube was placed in an oil bath at 60 °C for reaction, and the reaction was monitored by TLC. After the reaction was completed, the product was purified by column chromatography using petroleum ether / ethyl acetate = 20:1 as the eluent. The product 3c was obtained by column chromatography at a yield of 32.6 mg, which was 98%.

[0063] NMR data: 1 H NMR (400MHz, CDCl3, ppm): δ7.22-7.20 (m, 1H), 7.11-7.10 (d, 1H, J = 4Hz), 7.04 (s, 1H) ,6.94-6.91(m,1H),5.57(s,1H),3.86(s,3H),3.82(s,1H),3.77(s,3H),2.51(s,1H); 13 C{ 1 H}NMR (100MHz, CDCl3, ppm): δ135.2,132.1,128.0,125.9,112.9,112.4,110.6,101.3,80.0,70.7,59.9,55.9,33.3; 11 B{1 H}NMR(160MHz,CDCl3,ppm):-3.3(2B),-4.7(1B),-8.8(1B),-9.3(1B),-10.7(1B),-12.3(1B),-13.2(1B),-13.8(2B).HRMS(ESI)m / z calculated for C 13 B 10 H 22 NO2 - (MH) - 332.26592, found 332.26520.

[0064] Example 4:

[0065] 3D fabrication:

[0066]

[0067] Under air, 1-aldehyde-o-carborane 1a (17.2 mg, 0.1 mmol) and 6-chloro-1-methylindole 2d (19.9 mg, 0.12 mmol) were added sequentially to a dry 10 mL test tube. The test tube was placed in an oil bath at 60 °C for reaction, and the reaction was monitored by TLC. After the reaction was completed, the product was purified by column chromatography using petroleum ether / ethyl acetate = 20:1 as eluent. The product 3d was obtained in a yield of 21.6 mg, or 64%.

[0068] NMR data: 1 H NMR (400MHz, CDCl3, ppm): δ7.60-7.58 (m, 1H), 7.32-7.32 (d, 1H, J = 4Hz),, 7.15 -7.12(m,1H),7.07(s,1H),5.58(s,1H),3.85(s,1H),3.77(s,3H),2.04(s,1H); 13 C{ 1 H}NMR (100MHz, CDCl3, ppm): δ137.2,128.7,128.2,124.2,121.1,120.7,113.5,109.9,79.5,70.4,59.6,33.2; 11 B{ 1 H}NMR(160MHz,CDCl3,ppm):-3.3(2B),-4.6(1B),-8.8(1B),-9.3(1B),-11.0(1B),-12.3(1B),-13.2(1B),-13.9(2B).HRMS(ESI)m / z calculated for C12 H 19 B 10 NOCl - (MH) - 336.2164, found 336.2150.

[0069] Example 5:

[0070] Preparation of 3e:

[0071]

[0072] Under air, 1-aldehyde-o-carborane 1a (17.2 mg, 0.1 mmol) and 6-methyl-1-methylindole 2e (17.4 mg, 0.12 mmol) were added sequentially to a dry 10 mL test tube. The test tube was placed in an oil bath at 60 °C for reaction, and the reaction was monitored by TLC. After the reaction was completed, the product 3e was purified by column chromatography using petroleum ether / ethyl acetate = 20:1 as eluent. The product 3e was obtained in a yield of 31.4 mg, with a yield of 99%.

[0073] NMR data: 1 H NMR (500MHz, CDCl3, ppm): δ7.56-7.55 (d, 1H, J=5Hz), 7.12 (s, 1H), 7.02-7. 00(m,2H),5.59(s,1H),3.81(s,1H),3.76(s,3H),2.50(s,3H),2.46(s,1H); 13 C{ 1 H}NMR (125MHz, CDCl3, ppm): δ137.2,132.6,127.0,123.4,122.2,119.3,112.9,109.7,79.9,70.7,59.8,33.0,21.8; 11 B{ 1 H}NMR(160MHz,CDCl3,ppm):-3.3(2B),-4.7(1B),-8.9(1B),-9.4(1B),-10.8(1B),-12.3(1B),-13.3(1B),-13.9(2B).HRMS(ESI)m / z calculated forC 13 B 10 H 22 NO - (MH) - 316.27101, found 316.27112.

[0074] Example 6:

[0075] Preparation of 3f:

[0076]

[0077] Under air, 1-aldehyde-o-carborane 1a (17.2 mg, 0.1 mmol) and 2-methyl-1-methylindole 2f (17.4 mg, 0.12 mmol) were added sequentially to a dry 10 mL test tube. The test tube was placed in an oil bath at 60 °C for reaction, and the reaction was monitored by TLC. After the reaction was completed, the product was purified by column chromatography using petroleum ether / ethyl acetate = 20:1 as the eluent. The product 3f yielded 31.4 mg, with a yield of 99%.

[0078] NMR data: 1 H NMR (500MHz, CDCl3, ppm): δ7.79-7.77 (d, 1H, J = 10Hz), 7.30-7.28 (d, 1H, J = 10Hz), 7.23-7.19 (m,1H),7.15-7.11(m,1H),5.57(s,1H),3.88(s,1H),3.67(s,3H),2.60(s,1H),2.37(s,3H); 13 C{ 1 H}NMR (125MHz, CDCl3, ppm): δ136.9,135.5,124.6,121.6,120.3,119.9,109.3,108.9,80.6,71.7,59.0,11.2; 11 B{ 1 H}NMR(160MHz, CDCl3,ppm):-2.8(2B),-4.6(1B),-9.0(1B),-9.8(1B),-10.5(1B),-12.3(2B),-13.6(2B).HRMS(ESI)m / z calculated for C 13 H 24 B 10 NO + (M+H) + 318.2856, found 318.2865.

[0079] Example 7:

[0080] Preparation of 3g:

[0081]

[0082] Under air, 1-aldehyde-o-carborane 1a (17.2 mg, 0.1 mmol) and 2 g of methylindole (14.1 mg, 0.12 mmol) were added sequentially to a dry 10 mL test tube. The test tube was placed in an oil bath at 25 °C for reaction, and the reaction was monitored by TLC. After the reaction was completed, the product was purified by column chromatography using petroleum ether / ethyl acetate = 20:1 as the eluent. The product was obtained by column chromatography with a yield of 3 g (20.9 mg), which was 72%.

[0083] NMR data: 1 H NMR (400MHz, CDCl3, ppm): δ8.31 (s, 1H), 7.72-7.70 (d, 1H, J = 8Hz), 7.41-7.39 (d, 1 H, J=8Hz),7.24(m,1H),7.20-7.16(m,1H),5.65(s,1H),3.86(s,1H),2.62(s,1H); 13 C{ 1 H}NMR (125MHz, CDCl3, ppm): δ135.9,125.0,123.1,123.0,120.8,119.6,115.0,111.6,79.7,70.6,59.7; 11 B{ 1 H}NMR(160MHz, CDCl3, ppm):-3.3(2B),-4.7(1B),-8.9(1B),-9.4(1B),-10.9(1B),-12.3(1B),-13.3(1B),-13.9(2B).HRMS(ESI)m / z calculated for C 11 H 18 B 10 NO - (MH) - 289.2361, found 289.2372.

[0084] Example 8:

[0085] Preparation over 3 hours:

[0086]

[0087] Under air, 1-aldehyde-o-carborane 1a (17.2 mg, 0.1 mmol) and 1-butylindole 2h (21 mg, 0.12 mmol) were added sequentially to a dry 10 mL test tube. The test tube was placed in an oil bath at 60 °C for reaction, and the reaction was monitored by TLC. After the reaction was completed, the product was purified by column chromatography using petroleum ether / ethyl acetate = 20:1 as the eluent. The product 3h yielded 34.2 mg, with a yield of 99%.

[0088] NMR data: 1 H NMR (400MHz, CDCl3, ppm): δ7.69-7.67 (d, 1H, J = 8Hz), 7.36-7.34 (d, 1H, J = 8Hz), 7.28-7.24 (m, 1H), 7.18-7.14 (m, 1H), 7.13 (s, 1H), 5.62 (s,1H),4.14-4.10(dd,2H,J=8Hz,8Hz),3.83(s,1H),2.57(s,1H),1.86-1.78(m,2H),1.38-1.28(m,2H),0.97-0.93(dd,3H,J=8Hz,8Hz); 13 C{ 1 H}NMR (100MHz, CDCl3, ppm): δ136.0,126.7,125.7,122.4,120.3,119.7,112.9,110.0,79.9,70.7,59.7,46.3,32.1,20.1,13.6; 11 B{ 1 H}NMR(160MHz,CDCl3,ppm):-3.3(2B),-4.7(1B),-8.9(1B),-9.4(1B),-10.9(1B),-12.4(1B),-13.4(1B),-13.9(2B).HRMS(ESI)m / z calculated for C 15 B 10 H 26 NO - (MH) - 344.30231, found344.30219.

[0089] Example 9:

[0090] Preparation of 3i:

[0091]

[0092] Under air, 1-aldehyde-o-carborane 1a (17.2 mg, 0.1 mmol) and 1-benzylindole 2i (24.9 mg, 0.12 mmol) were added sequentially to a dry 10 mL test tube. The test tube was placed in an oil bath at 60 °C for reaction, and the reaction was monitored by TLC. After the reaction was completed, the product was purified by column chromatography using petroleum ether / ethyl acetate = 20:1 as the eluent. The product 3i yielded 37.5 mg, with a yield of 99%.

[0093] NMR data: 1H NMR (400MHz, CDCl3, ppm): δ7.72-7.70 (d, 1H, J = 8Hz), 7.32-7.29 (m, 4H), 7.24-7.17 (m, 2 H),7.16(s,1H),7.10-7.08(m,2H),5.64(s,1H),5.32(s,2H),3.88(s,1H),2.58(s,1H); 13 C{ 1 H}NMR (125MHz, CDCl3, ppm): δ136.6,136.5,129.0,128.0,127.0,126.8,122.8,120.6,119.8,113.9,110.3,88.6,70.6,59.6,50.3; 11 B{ 1 H}NMR(160MHz,CDCl3,ppm):-3.3(2B),-4.6(1B),-8.9(1B),-9.4(1B),-11.0(1B),-12.3(1B),-13.2(1B),-13.9(2B).HRMS(ESI)m / z calculated for C 18 B 10 H 26 NO + (M+H) + 380.30176, found 380.30121.

[0094] Example 10:

[0095] Preparation of 3j:

[0096]

[0097] Under air, 1-aldehyde-o-carborane 1a (17.2 mg, 0.1 mmol) and 1-phenylindole 2j (23.2 mg, 0.12 mmol) were added sequentially to a dry 10 mL test tube. The test tube was placed in an oil bath at 60 °C for reaction, and the reaction was monitored by TLC. After the reaction was completed, the product was purified by column chromatography using petroleum ether / ethyl acetate = 20:1 as the eluent. The product 3j was obtained in a yield of 29.9 mg, with a yield of 82%.

[0098] NMR data: 1H NMR (400MHz, CDCl3, ppm): δ7.76-7.74(m,1H),7.57-7.52(m,3H),7.49-7.47(m,2H),7.44-7.40( m,1H),7.38(s,1H),7.29-7.27(m,1H),7.25-7.21(m,1H),5.71(s,1H),3.95(s,1H),2.64(s,1H); 13 C{ 1 H}NMR (125MHz, CDCl3, ppm): δ138.8,136.1,129.8,127.3,126.8,126.3,124.6,123.4,121.3,119.9,115.5,111.1,79.5,70.5,59.7; 11 B{ 1 H}NMR(160MHz,CDCl3,ppm):-3.2(2B),-4.6(1B),-8.8(1B),-9.3(1B),-10.9(1B),-12.2(1B),-13.2(1B),-13.8(2B).HRMS(ESI)m / z calculated for C 17 B 10 H 24 NO + (M+H) + 366.28611, found 366.28491.

[0099] Example 11:

[0100] Preparation of 5a:

[0101]

[0102] Under air, 1-methyl-2-aldehyde-o-carborane 4a (18.6 mg, 0.1 mmol) and 1-methylindole 2a (15.7 mg, 0.12 mmol) were added sequentially to a dry 10 mL test tube. The test tube was placed in an oil bath at 60 °C for reaction, and the reaction was monitored by TLC. After the reaction was completed, the product was purified by column chromatography using petroleum ether / ethyl acetate = 20:1 as eluent. The product 5a was obtained in 31.5 mg, with a yield of 99%.

[0103] NMR data: 1H NMR (500MHz, CDCl3, ppm): δ7.69-7.68 (d, 1H, J = 10Hz), 7.35-7.33 (d, 1H, J = 10Hz), 7.29-7.28 (m,1H),7.20-7.17(m,1H),7.16(s,1H),5.51(s,1H),3.82(s,3H),2.38(s,1H),2.25(s,3H); 13 C{ 1 H}NMR (125MHz, CDCl3, ppm): δ136.6,127.8,125.9,122.4,120.2,119.4,114.6,109.8,82.7,74.4,68.9,33.1,23.6; 11 B{ 1 H}NMR(160MHz, CDCl3,ppm):-3.1(2B),-5.5(2B),-9.4(1B),-9.9(2B),-10.6(1B),-11.2(1B),-11.8(1B).HRMS(ESI)m / z calculated for C 13 H 24 B 10 NO + (M+H) + 319.2819, found 319.2862.

[0104] Example 12:

[0105] Preparation of 5b:

[0106]

[0107] Under air, 1-phenyl-2-aldehyde-o-carborane 4b (24.8 mg, 0.1 mmol) and 1-methylindole 2a (15.7 mg, 0.12 mmol) were added sequentially to a dry 10 mL test tube. The test tube was placed in an oil bath at 60 °C for reaction, and the reaction was monitored by TLC. After the reaction was completed, the product was purified by column chromatography using petroleum ether / ethyl acetate = 20:1 as the eluent. The product 5b was obtained in a yield of 36.4 mg, with a yield of 96%.

[0108] NMR data: 1H NMR (400MHz, CDCl3, ppm): δ7.81-7.78(m,2H),7.55-7.51(m,1H),7.48-7.44(m,3H),7.30-7.28( m,1H),7.23-7.21(m,1H),7.13-7.09(m,1H),6.84(s,1H),4.83(s,1H),3.74(s,3H),2.14(s,1H); 13 C{ 1 H}NMR (125MHz, CDCl3, ppm): δ136.5,131.4,131.0,130.8,129.0,127.8,125.7,122.2,119.9,119.6,114.1,109.6,87.3,83.8,68.1,33.0; 11 B{ 1 H}NMR(160MHz, CDCl3,ppm):-2.3(2B),-3.8(2B),-9.6(3B),-10.6(1B),-12.0(2B).HRMS(ESI)m / z calculated for C 18 B 10 H 24 NO - (MH) - 378.28666, found 378.28604.

[0109] Example 13:

[0110] Preparation of 5c:

[0111]

[0112] Under air, 1-(3-fluoro-phenyl)-2-aldehyde-o-carborane 4c (26.7 mg, 0.1 mmol) and 1-methylindole 2a (15.7 mg, 0.12 mmol) were added sequentially to a dry 10 mL test tube. The test tube was placed in an oil bath at 60 °C for reaction, and the reaction was monitored by TLC. After the reaction was completed, the product was purified by column chromatography using petroleum ether / ethyl acetate = 20:1 as the eluent. The product 5c 39 mg was obtained by column chromatography, with a yield of 98%.

[0113] NMR data: 1H NMR (500MHz, CDCl3, ppm): δ7.61-7.59 (d, 1H, J = 10Hz), 7.52-7.43 (m, 3H), 7.31-7.29 (m, 1H) ,7.25-7.21(m,2H),7.15-7.11(m,1H),6.86(s,1H),4.85(s,1H),3.75(s,3H),2.20(s,1H); 13 C{ 1 H}NMR (125MHz, CDCl3, ppm): δ162.4 (J=246.3Hz), 136.6, 133.2 (J=7.5Hz), 130.4 (J=8.8Hz), 127.8, 127.1 (J=2 .5Hz),125.6,122.3,120.0,119.9,118.7(J=2.4Hz),117.9(J=21.3Hz),114.0,109.7,87.3,82.2,68.3,33.0; 11 B{ 1 H}NMR(160MHz, CDCl3,ppm):-2.3(2B),-3.5(2B),-9.5(3B),-10.6(1B),-11.9(2B).HRMS(ESI)m / z calculated for C 18 H 25 B 10 NOF + (M+H) + 399.2887, found 399.2934.

[0114] Example 14:

[0115] Preparation of 5d:

[0116]

[0117] Under air, 1-(4-bromophenyl)-2-aldehyde-o-carborane 4d (32.8 mg, 0.1 mmol) and 1-methylindole 2a (15.7 mg, 0.12 mmol) were added sequentially to a dry 10 mL test tube. The test tube was placed in an oil bath at 60 °C for reaction, and the reaction was monitored by TLC. After the reaction was completed, the product was purified by column chromatography using petroleum ether / ethyl acetate = 20:1 as the eluent. The product 5d was obtained at a yield of 42.6 mg, with a yield of 93%.

[0118] NMR data: 1H NMR (500MHz, CDCl3, ppm): δ7.65-7.63 (m, 2H), 7.59-7.56 (m, 2H), 7.47-7.45 (d, 1H, J = 10Hz), 7.31-7. 29(m,1H),7.25-7.23(m,1H),7.15-7.11(m,1H),6.84(s,1H),4.83(s,1H),3.75(s,3H),2.18(s,1H); 13 C{ 1 H}NMR (125MHz, CDCl3, ppm): δ136.5,132.9,132.0,130.1,127.8,125.7,125.6,122.3,120.0,119.5,114.0,109.7,87.2,82.5,68.3,33.0; 11 B{ 1 H}NMR(160MHz, CDCl3,ppm):-2.3(2B),-3.5(2B),-9.6(3B),-10.7(1B),-11.9(2B).HRMS(ESI)m / z calculated for C 18 B 10 H 23 NOBr - (MH) - 457.19354, found 457.19437.

[0119] Example 15:

[0120] Preparation of 5e:

[0121]

[0122] Under air, 1-(4-methoxy-phenyl)-2-aldehyde-o-carborane 4e (27.8 mg, 0.1 mmol) and 1-methylindole 2a (15.7 mg, 0.12 mmol) were added sequentially to a dry 10 mL test tube. The test tube was placed in an oil bath at 60 °C for reaction, and the reaction was monitored by TLC. After the reaction was completed, the product was purified by column chromatography using petroleum ether / ethyl acetate = 20:1 as eluent. The product 5e was obtained in 39.3 mg, with a yield of 96%.

[0123] NMR data: 1H NMR (500MHz, CDCl3, ppm): δ7.72-7.68(m,2H),7.48-7.46(d,1H,J=10Hz),7.30-7.28(m,1H),7.25-7.21(m, 1H),7.13-7.09(m,1H),6.97-6.93(m,2H),6.88(s,1H),4.83(s,1H),3.88(s,3H),3.75(s,3H),2.05(s,1H); 13 C{ 1 H}NMR (125MHz, CDCl3, ppm): δ136.5,132.8,127.8,125.8,123.0,122.2,119.9,119.7,114.2,109.6,87.5,84.3,68.0,55.5,33.0; 11 B{ 1 H}NMR(160MHz, CDCl3,ppm):-2.3(2B),-4.2(2B),-9.8(3B),-10.8(1B),-12.1(2B).HRMS(ESI)m / z calculated for C 19 H 28 B 10 NO2 + (M+H) + 410.3118, found 410.3123.

[0124] Although embodiments of the present invention have been disclosed above, they are not limited to the applications listed in the specification and embodiments. They can be applied to various fields suitable for the present invention. For those skilled in the art, other modifications can be easily made. Therefore, without departing from the general concept defined by the claims and their equivalents, the present invention is not limited to the specific details and illustrations shown and described herein.

Claims

1. A 3-indole- o A green synthesis method for carborane methanol derivatives, characterized in that, include: by and Using raw materials, under air atmosphere and a certain temperature, through C3-H The nucleophilic addition reaction of the aldehyde group efficiently synthesized 3-indole- o -Carborane methanol derivative; the 3-indole- o The general structural formula for carborane methanol derivatives is: ； Wherein R1 is any one of alkyl, alkoxy, or halogen; R2 is any one of methyl, n-butyl, benzyl, phenyl, or hydrogen; and R3 is any one of methyl, phenyl, or substituted phenyl. The The preparation method includes the following steps: Step 1: Add to a dry reaction vessel Under argon protection, dry diethyl ether was added as a solvent, and the reaction system was placed at -78°C. N-butyllithium was slowly added dropwise using a dry syringe. After the system reacted at -78°C for 1 h, methyl formate was added, and the reaction continued at -78°C for 2 h. The reaction progress was monitored by TLC plate. Step 2: After the reaction is complete and the system is brought to room temperature, hydrochloric acid is added to quench the reaction. Then, the reaction is extracted with ethyl acetate. The organic phase is washed three times with saturated NaHCO3 solution and saturated NaCl aqueous solution, respectively. The organic phase is collected and dried with anhydrous sodium sulfate. Step 3: Remove the organic solvent by vacuum distillation, using petroleum ether and ethyl acetate as eluents, and separate by column chromatography to obtain a white solid, which is... .

2. The 3-indole- as described in claim 1 o A green synthesis method for carborane methanol derivatives, characterized in that, The specified temperature is 25~60℃.

3. The 3-indole- as described in claim 1 o- A green synthesis method for carborane methanol derivatives, characterized in that, The In this context, R3 can be any one of methyl, phenyl, or substituted phenyl.

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