A method for preparing a 2-tert-butylaminobenzaldehyde derivative

Abstract

The application belongs to the technical field of organic synthesis, and particularly relates to a preparation method of 2-tert-butyl aminophenyl aldehyde derivatives. N,N-di-tert-butyl urea, tert-butyl hypochlorite, potassium tert-butoxide and triethylamine are mixed and reacted in anhydrous ether to obtain compound III, the structural formula of which is compound III is mixed with compound II, a ruthenium catalyst, amine, an additive, a base, and a solvent in a molar ratio of (2.0-2.5):1:(0.08-0.1):1:(1.5-2.0):(3.0-4.0), and then subjected to amination reaction at 125-135 DEG C under an inert atmosphere for 10-14 h to obtain 2-tert-butyl aminophenyl aldehyde derivatives, the structural formula of compound II is wherein R1 represents a hydrogen atom, a methyl group, a phenyl group, a methoxy group, a fluorine atom, a chlorine atom, a methyl ester group or a cyano group; R2 represents a hydrogen atom; and R3 represents a hydrogen atom or a phenyl group.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of organic synthesis, and particularly relates to a preparation method of 2-tert-butyl aminophenyl aldehyde derivatives. BACKGROUND

[0002] O-aminobenzaldehyde compounds are an important class of organic functional group intermediates, and as active molecules, have important applications in the fields of medicine, pesticide, organic synthesis and the like, and can be used for the synthesis of quinoline and its derivatives and other nitrogen-containing heterocyclic compounds. Therefore, the synthesis of O-aminobenzaldehyde derivatives has been highly valued by a large number of chemical workers. The reduction reaction of O-nitrobenzaldehyde derivatives is one of the main methods for preparing O-aminobenzaldehyde derivatives, but has defects such as harsh reaction conditions and many side reactions. SUMMARY

[0003] To solve the above technical problems, the application provides a preparation method of 2-tert-butyl aminophenyl aldehyde derivatives, which is simple in operation, has few side reactions, has excellent yield, and can directly prepare a series of 2-tert-butyl aminophenyl aldehyde derivatives through C-H amination of the ortho position of benzaldehyde:

[0004] (1) mixing N,N-di-tert-butyl urea, tert-butyl hypochlorite, potassium tert-butoxide and triethylamine in anhydrous ether to obtain compound III, and the structural formula of compound III is

[0005] (2) mixing compound III obtained in step (1), compound II, a ruthenium catalyst, an amine, an additive and a base in a solvent, and then performing amination reaction under an inert atmosphere to obtain a 2-tert-butyl aminophenyl aldehyde derivative,

[0006] the structural formula of compound II is wherein R1 represents a hydrogen atom, a methyl group, a phenyl group, a methoxy group, a fluorine atom, a chlorine atom, a methyl ester group or a cyano group; R2 represents a hydrogen atom; and R3 represents a hydrogen atom or a phenyl group,

[0007] The synthesis reaction formula is as follows:

[0008]

[0009] As preferred: in step (1), N,N-di-tert-butyl urea is obtained by mixing tert-butyl amine, triethylene diamine, di-tert-butyl dicarbonate and dichloromethane at room temperature (25 DEG C, the same below).

[0010] As preferred: in step (2), the molar ratio among compound II, the ruthenium catalyst, the amine, the additive, the base and compound III is 1:(0.08-0.1):1:(1.5-2.0):(3.0-4.0):(2.0-2.5).

[0011] As preferred: in step (2), the concentration of compound II in the solvent is 0.2 mol / L.

[0012] As preferred: the ruthenium catalyst in step (2) is triruthenium dodecacarbonyl.

[0013] As preferred: the amine in step (2) is 2-methoxyethylamine.

[0014] As preferred: the additive in step (2) is 2,4,6-trimethylbenzoic acid.

[0015] As preferred: the base in step (2) is cesium fluoride.

[0016] As preferred: the solvent in step (2) is 1,4-dioxane or p-xylene.

[0017] As preferred: in step (2), the reaction temperature of the amination reaction is 125-135 DEG C, and the reaction time is 10-14 h.

[0018] The specific synthesis mechanism of the scheme is that:

[0019]

[0020] In the scheme, the substrate compound II is condensed with 2-methoxyethylamine to form imine 1, which is then complexed with a ruthenium catalyst to generate ortho-activated ruthenium ring intermediate 3 through carbon-hydrogen activation, which is oxidatively added with a three-membered ring nitrogen-containing reagent compound III to generate the corresponding ruthenium intermediate 4, which is then released tBuNCO to obtain nitrogen bin intermediate 5, which is then reduced and eliminated to obtain the amination product 7 and the ruthenium catalyst, and the amination product 7 is hydrolyzed by silica gel column to generate the corresponding amination product I; the methoxy imine has the function of a directing group.

[0021] In the preparation method of the present application, the initial substrate benzaldehyde compound II is simple and easy to obtain, has a wide substrate range, simple synthesis operation, few side reactions, excellent yield, does not need to be pre-substituted with a specific functional group at the to-be-reacted carbon position, can directly aminate the aryl C-H bond, and can synthesize 2-tert-butylamine benzaldehyde derivatives with diverse types of substituents.

[0022] In the present application, N,N-di-tert-butyl dinitrogen heterocyclic ketone is used as a nitrogen source, and the prepared 2-tert-butylamine benzaldehyde derivative contains N-tert-butyl, which is easy to remove and can also be used as a protecting group in the arylamine nitrogen, and has a good protective effect in the further derivatization reaction of the 2-tert-butylamine benzaldehyde derivative. DETAILED DESCRIPTION

[0023] All reagents used in the following examples are commercially available. Specifically, dodecyltriruthenium carbonyl and 2-methoxyethylamine were purchased from Bide reagent, 2,4,6-trimethylbenzoic acid was purchased from Leyan reagent, and cesium fluoride was purchased from 3AChemical.

[0024] Example 1

[0025] (1) Preparation of compound III:

[0026]

[0027] 52.5 mL of tert-butylamine (500.0 mmol), 5.6 g of triethylenediamine (DABCO) (250.0 mmol), and 200.0 mL of dichloromethane were added to the reactor. Then, 57.5 mL of ditert-butyl dicarbonate (50.0 mmol) was dissolved in 50 mL of dichloromethane and added to the reactor. The mixture was stirred at room temperature for 12 h. After the reaction, the reaction solution in the reactor was cooled to 0 °C, and 250 mL of n-hexane was added to it to facilitate the precipitation of the target product. The mixture was then filtered, and the filter cake was washed successively with supercooled water and diethyl ether to obtain a white solid N,N-ditert-butylurea.

[0028] The N,N-di-tert-butylurea (20.0 g, 116.1 mmol) and diethyl ether prepared above were added to another reactor.

[0029] (200.0 mL) was added dropwise, followed by tert-butyl hypochlorite (13.9 mL, 127.7 mmol), then triethylamine (0.16 mL, 2 mmol). After stirring at room temperature for 30 minutes, the reaction solution in the reactor was cooled to 5°C. Potassium tert-butoxide (17.0 g, 150.9 mmol) was then slowly added. The mixture was allowed to warm naturally to room temperature and stirred for 12 hours. 150 mL of n-hexane was added to the resulting reaction solution, which was washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and distilled under reduced pressure to give compound III as a colorless liquid (11.6 g, yield 59%).

[0030] NMR data of compound III: 1 H NMR (400MHz, CDCl3): δ1.30 (s, 18H); 13 C NMR (100MHz, CDCl3): δ158.8, 59.1, 26.8.

[0031] (2) Preparation of compound Ia:

[0032]

[0033] In a 15 mL pressure tube, compound II-a (0.0424 g, 0.4 mmol), triruthenium dodecacarbonyl (0.0205 g, 0.032 mmol), 2-methoxyethylamine (0.030 g, 0.4 mmol), 2,4,6-trimethylbenzoic acid (0.1314 g, 0.8 mmol), cesium fluoride (0.2430 g, 1.6 mmol) were added successively, vacuumed and filled with argon, then compound III (0.1362 g, 0.8 mmol) prepared in step (1) was added successively, sealed and stirred in a magnetic heating stirrer at 130°C for 12 hours. After the reaction was completed, the reaction solution was cooled to room temperature, diluted with ethyl acetate, filtered through 300-400 mesh silica gel, eluted with ethyl acetate (the excess compound III in the reaction was degraded to open ring to form urea, and the urea was eluted with ethyl acetate due to its large polarity, and the same was true below), concentrated under reduced pressure to remove the solvent, diluted with dichloromethane, and stirred with 200-300 mesh silica gel, and then dried and loaded onto a 300-400 mesh silica gel column for chromatographic separation (eluent: petroleum ether: ethyl acetate = 50:1 (by volume), and the urea could not be eluted due to the smaller polarity of the eluent, thus achieving separation from the target product, and the same was true below), to obtain compound I-a (0.0305 g, yield 43%) in the form of a light yellow solid.

[0034] NMR data of compound I-a: 1 H NMR (400 MHz, CDCl3) δ 9.77 (s, 1H), 8.65 (br s, 1H), 7.43 (dd, J = 8.0, 2.0 Hz, 1H), 7.33 (ddd, J = 8.8, 6.8, 1.6 Hz, 1H), 6.91 (d, J = 8.8 Hz, 1H), 6.64 (t, J = 7.6 Hz, 1H), 1.46 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 194.0, 150.2, 137.7, 135.1, 119.0, 114.2, 113.3, 50.9, 29.6.

[0035] Comparative Example 1

[0036] The catalyst used in step (2) was replaced with “ruthenium chloride”, and the rest of the operations were the same as in Example 1:

[0037] (1) Preparation of compound III: same as in Example 1, step (1);

[0038] (2) Into a 15 mL pressure tube, compound II-a (0.0424 g, 0.4 mmol), ruthenium chloride (0.0066 g, 0.032 mmol), 2-methoxyethylamine (0.030 g, 0.4 mmol), 2,4,6-trimethylbenzoic acid (0.1314 g, 0.8 mmol), cesium fluoride (0.2430 g, 1.6 mmol) were added successively, vacuumed and filled with argon, then compound III (0.1362 g, 0.8 mmol) prepared in step (1) and super dry 1,4-dioxane (2.0 mL) were added successively, sealed and stirred in a magnetic heating stirrer at 130 °C for 12 hours. After the reaction was completed, the reaction solution was cooled to room temperature, diluted with ethyl acetate, filtered through 300-400 mesh silica gel, eluted with ethyl acetate, concentrated under reduced pressure to remove the solvent, diluted with dichloromethane, and mixed with 200-300 mesh silica gel, dried and loaded onto a 300-400 mesh silica gel column, and separated by column chromatography (eluent: petroleum ether: ethyl acetate = 50: 1, by volume) to obtain 6.1 mg of a yellow solid product, which was analyzed by NMR to be compound I-a, and the yield was calculated to be 8.6%.

[0039] Comparative Example 2

[0040] The catalyst used in step (2) was replaced with "palladium bromide", and the rest of the operations were the same as in Example 1.

[0041] (1) Preparation of compound III: same as in Example 1, step (1);

[0042] (2) Into a 15 mL pressure tube, compound II-a (0.0424 g, 0.4 mmol), palladium bromide (0.0085 g, 0.032 mmol), 2-methoxyethylamine (0.030 g, 0.4 mmol), 2,4,6-trimethylbenzoic acid (0.1314 g, 0.8 mmol), cesium fluoride (0.2430 g, 1.6 mmol) were added successively, vacuumed and filled with argon, then compound III (0.1362 g, 0.8 mmol) prepared in step (1) and super dry 1,4-dioxane (2.0 mL) were added successively, sealed and stirred in a magnetic heating stirrer at 130 °C for 12 hours. After the reaction was completed, the reaction solution was cooled to room temperature, diluted with ethyl acetate, filtered through 300-400 mesh silica gel, eluted with ethyl acetate, concentrated under reduced pressure to remove the solvent, diluted with dichloromethane, and mixed with 200-300 mesh silica gel, dried and loaded onto a 300-400 mesh silica gel column, and separated by column chromatography (eluent: petroleum ether: ethyl acetate = 50: 1, by volume) to obtain 6.1 mg of a yellow solid product, which was analyzed by NMR to be compound I-a, and the yield was calculated to be 8.6%.

[0043] From Comparative Example 1 and Comparative Example 2, it can be seen that in the present application, when the imine synthesized by condensation of 2-methoxyethylamine and benzaldehyde is used to guide the synthesis reaction with the triatomic ring nitrogen source compound III, the use of palladium metal catalyst cannot smoothly achieve catalysis, and when a general ruthenium metal salt is used as the catalyst, the catalytic effect is also very low, and the amount of product generated by catalysis is very small, and only when the carbon oxide compound of ruthenium is used as the catalyst, can effective catalytic effect be obtained.

[0044] Example 2

[0045] (1) Preparation of compound III: same as step (1) of Example 1;

[0046] (2) Preparation of compound I-b:

[0047]

[0048] In a 15 mL pressure tube, compound II-b (0.0481 g, 0.4 mmol), triruthenium dodecacarbonyl (0.0205 g, 0.032 mmol), 2-methoxyethylamine (0.030 g, 0.4 mmol), 2,4,6-trimethylbenzoic acid (0.1314 g, 0.8 mmol), cesium fluoride (0.2430 g, 1.6 mmol) were sequentially added, vacuumed and filled with argon, then ultra-dry 1,4-dioxane (2.0 mL) and compound III (0.1362 g, 0.8 mmol) prepared in step (1) were sequentially added, sealed and placed in a magnetic heating stirrer for stirring at 130°C for 12 hours. After the reaction was completed, the obtained reaction solution was cooled to room temperature, diluted with ethyl acetate, filtered through 300-400 mesh silica gel, eluted with ethyl acetate, concentrated under reduced pressure to remove the solvent, diluted with dichloromethane, and then mixed with 200-300 mesh silica gel, dried and loaded onto a column, and separated by column chromatography (eluent: petroleum ether: ethyl acetate = 50:1, by volume) to obtain compound I-b (0.030 g, yield 39%) in the form of light yellow oil.

[0049] NMR data of compound I-b: 1 H NMR (400 MHz, CDCl3) δ 9.70 (s, 1H), 8.64 (br s, 1H), 7.31 (d, J = 8.0 Hz, 1H), 6.70 (d, J = 1.6 Hz, 1H), 6.46 (dd, J = 8.0, 1.6 Hz, 1H), 2.33 (s, 3H), 1.46 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 193.2, 150.3, 146.3, 137.7, 117.2, 115.8, 113.5, 50.9, 29.6, 22.8.

[0050] (1) Preparation of compound III: same as step (1) of example 1;

[0051] (2) Preparation of compound I-c:

[0052]

[0053] In a 15 mL pressure tube, compound II-c (0.0729 g, 0.4 mmol), tris-ruthenium dodecacarbonyl (0.0205 g, 0.032 mmol), 2-methoxyethylamine (0.030 g, 0.4 mmol), 2,4,6-trimethylbenzoic acid (0.1314 g, 0.8 mmol), cesium fluoride (0.2430 g, 1.6 mmol) were added successively, vacuumed and filled with argon, then compound III (0.1362 g, 0.8 mmol) prepared in step (1) was added successively, sealed and stirred in a magnetic heating stirrer at 130 °C for 12 hours. After the reaction was completed, it was cooled to room temperature, and the resulting reaction solution was diluted with ethyl acetate, filtered through 300-400 mesh silica gel, eluted with ethyl acetate, concentrated under reduced pressure to remove the solvent, diluted with dichloromethane, and stirred with 200-300 mesh silica gel, dried and loaded onto a column, and separated by column chromatography on 300-400 mesh silica gel (eluent: petroleum ether: ethyl acetate = 50:1, by volume) to obtain compound I-c (0.0667 g, yield 67%) as a light yellow oil.

[0054] NMR data of compound I-c: 1 H NMR (400 MHz, CDCl3) δ 9.81 (s, 1H), 8.73 (br s, 1H), 7.65-7.58 (m, 2H), 7.52-7.39 (m, 4H), 7.10 (d, J = 1.6 Hz, 1H), 6.87 (dd, J = 8.0, 1.6 Hz, 1H), 1.52 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 193.5, 150.3, 147.8, 141.1, 138.1, 129.0, 128.4, 127.5, 118.1, 113.7, 111.9, 51.0, 29.7.

[0055] Example 4

[0056] (1) Preparation of compound III: same as step (1) of example 1;

[0057] (2) Preparation of compound I-d:

[0058]

[0059] In a 15 mL pressure tube, compound II-d (0.0545 g, 0.4 mmol), triruthenium dodecacarbonyl (0.0205 g, 0.032 mmol), 2-methoxyethylamine (0.030 g, 0.4 mmol), 2,4,6-trimethylbenzoic acid (0.1314 g, 0.8 mmol), cesium fluoride (0.2430 g, 1.6 mmol) were added successively, vacuumed and filled with argon, then compound III (0.1362 g, 0.8 mmol) prepared in step (1) was added successively, sealed and stirred in a magnetic heating stirrer at 130 °C for 12 hours. After the reaction was completed, the resulting reaction solution was diluted with ethyl acetate, filtered through 300-400 mesh silica gel, eluted with ethyl acetate, concentrated under reduced pressure to remove the solvent, diluted with dichloromethane, and stirred with 200-300 mesh silica gel, dried and loaded onto a column, and separated by column chromatography on 300-400 mesh silica gel (eluent: petroleum ether: ethyl acetate = 50:1, by volume), to obtain compound I-d (0.0350 g, yield 42%) as a light yellow oil.

[0060] NMR data of compound I-d: 1 H NMR (400 MHz, CDC13) δ 9.60 (s, 1H), 8.78 (br s, 1H), 7.32 (d, J = 8.8 Hz, 1H), 6.30 (d, J = 2.4 Hz, 1H), 6.22 (dd, J = 8.8, 2.4 Hz, 1H), 3.84 (s, 3H), 1.46 (s, 9H); 13 C NMR (100 MHz, CDC13) δ 191.8, 165.1, 151.9, 139.8, 114.3, 102.1, 96.9, 55.4, 50.8, 29.4.

[0061] (1) Preparation of compound III: same as step (1) of Example 1;

[0062] (2) Preparation of compound I-e:

[0063]

[0064] In a 15 mL pressure tube, compound II-e (0.0496 g, 0.4 mmol), triruthenium dodecacarbonyl (0.0205 g, 0.032 mmol), 2-methoxyethylamine (0.030 g, 0.4 mmol), 2,4,6-trimethylbenzoic acid (0.1314 g, 0.8 mmol), cesium fluoride (0.2430 g, 1.6 mmol) were added successively, vacuumed and filled with argon, then compound III (0.1362 g, 0.8 mmol) prepared in step (1) was added successively, sealed and stirred in a magnetic heating stirrer at 130 °C for 12 hours. After the reaction was completed, the resulting reaction solution was diluted with ethyl acetate, filtered through 300-400 mesh silica gel, eluted with ethyl acetate, concentrated under reduced pressure to remove the solvent, diluted with dichloromethane, and stirred with 200-300 mesh silica gel, dried and loaded onto a column, and separated by column chromatography (300-400 mesh silica gel, eluent: petroleum ether: ethyl acetate = 50:1, by volume) to obtain compound I-e (0.0370 g, yield 47%) as a light yellow oil.

[0065] NMR data of compound I-e: 1 H NMR (400 MHz, CDC13) δ 9.69 (s, 1H), 8.86 (br s, 1H), 7.41 (dd, J = 8.8, 6.8 Hz, 1H), 6.53 (dd, J = 12.8, 2.4 Hz, 1H), 6.33 (td, J = 8.0, 2.4 Hz, 1H), 1.45 (s, 9H); 13 C NMR (100 MHz, CDC13) δ 192.6, 167.4 (d, J = 251.5 Hz), 152.0 (d, J = 13.6 Hz), 140.5 (d, J = 13.2 Hz), 116.4, 102.6 (d, J = 23.7 Hz), 99.4 (d, J = 26.3 Hz), 51.2, 29.3.

[0066] Example 6

[0067] (1) Preparation of compound III: same as step (1) of Example 1;

[0068] (2) Preparation of compound I-f:

[0069]

[0070] In a 15 mL pressure tube, compound II-f (0.0562 g, 0.4 mmol), triruthenium dodecacarbonyl (0.0205 g, 0.032 mmol), 2-methoxyethylamine (0.030 g, 0.4 mmol), 2,4,6-trimethylbenzoic acid (0.1314 g, 0.8 mmol), cesium fluoride (0.2430 g, 1.6 mmol) were added successively, vacuumed and filled with argon, then compound III (0.1362 g, 0.8 mmol) prepared in step (1) was added successively, sealed and stirred in a magnetic heating stirrer at 130 °C for 12 hours. After the reaction was completed, the resulting reaction solution was diluted with ethyl acetate, filtered through 300-400 mesh silica gel, eluted with ethyl acetate, concentrated under reduced pressure to remove the solvent, diluted with dichloromethane, and stirred with 200-300 mesh silica gel, dried and loaded onto a column, and separated by column chromatography (300-400 mesh silica gel, eluent: petroleum ether: ethyl acetate = 50: 1, volume ratio) to obtain compound I-f (0.0406 g, yield 48%) as a light yellow oil.

[0071] NMR data of compound I-f: 1 H NMR (400 MHz, CDC13) δ 9.71 (s, 1H), 8.74 (br s, 1H), 7.34 (d, J = 8.4 Hz, 1H), 6.87 (d, J = 1.6 Hz, 1H), 6.60 (dd, J = 8.4, 2.0 Hz, 1H), 1.45 (s, 9H); 13 CNMR (100 MHz, CDC13) δ 193.0, 150.5, 141.8, 138.9, 117.6, 114.8, 112.9, 51.2, 29.4.

[0072] Example 7

[0073] (1) Preparation of compound III: same as step (1) of Example 1;

[0074] (2) Preparation of compound I-g:

[0075]

[0076] In a 15 mL pressure tube, compound II-g (0.0657 g, 0.4 mmol), triruthenium dodecacarbonyl (0.0205 g, 0.032 mmol), 2-methoxyethylamine (0.030 g, 0.4 mmol), 2,4,6-trimethylbenzoic acid (0.1314 g, 0.8 mmol), cesium fluoride (0.2430 g, 1.6 mmol) were added successively, vacuumed and filled with argon, then compound III (0.1362 g, 0.8 mmol) prepared in step (1) was added successively, sealed and stirred in a magnetic heating stirrer at 130 °C for 12 hours. After the reaction was completed, the resulting reaction solution was diluted with ethyl acetate, filtered through 300-400 mesh silica gel, eluted with ethyl acetate, concentrated under reduced pressure to remove the solvent, diluted with dichloromethane, and stirred with 200-300 mesh silica gel, dried and loaded onto a column, and separated by column chromatography on 300-400 mesh silica gel (eluent: petroleum ether: ethyl acetate = 50:1, by volume), to obtain compound I-g (0.0365 g, yield 39%) as a light yellow oil.

[0077] NMR data of compound I-g: 1 H NMR (400 MHz, CDC13) δ 9.85 (s, 1H), 8.64 (br s, 1H), 7.60 (d, J = 1.6 Hz, 1H), 7.50 (d, J = 8.0 Hz, 1H), 7.23 (dd, J = 8.4, 1.6 Hz, 1H), 3.92 (s, 3H), 1.48 (s, 9H); 13 C NMR (100 MHz, CDC13) δ 194.0, 166.9, 149.6, 137.6, 135.3, 121.0, 114.9, 114.3, 52.6, 51.2, 29.6.

[0078] Example 8

[0079] (1) Preparation of compound III: same as step (1) of Example 1;

[0080] (2) Preparation of compound I-h:

[0081]

[0082] In a 15 mL pressure tube, compound II-h (0.0525 g, 0.4 mmol), triruthenium dodecacarbonyl (0.0205 g, 0.032 mmol), 2-methoxyethylamine (0.030 g, 0.4 mmol), 2,4,6-trimethylbenzoic acid (0.1314 g, 0.8 mmol), cesium fluoride (0.2430 g, 1.6 mmol) were added successively, vacuumed and filled with argon, then compound III (0.1362 g, 0.8 mmol) prepared in step (1) was added successively, sealed and stirred in a magnetic heating stirrer at 130 °C for 12 hours. After the reaction was completed, the resulting reaction solution was diluted with ethyl acetate, filtered through 300-400 mesh silica gel, eluted with ethyl acetate, concentrated under reduced pressure to remove the solvent, diluted with dichloromethane, and stirred with 200-300 mesh silica gel, dried and loaded onto a column, and separated by column chromatography (300-400 mesh silica gel, eluent: petroleum ether: ethyl acetate = 50: 1, volume ratio) to obtain compound I-h (0.030 g, yield 37%) as a light yellow oil.

[0083] NMR data of compound I-h: 1 H NMR (400 MHz, CDC13) δ 9.82 (s, 1H), 8.74 (br s, 1H), 7.52 (d, J = 8.0 Hz, 1H), 7.14 (d, J = 1.6 Hz, 1H), 6.85 (dd, J = 7.6, 1.2 Hz, 1H), 1.46 (s, 9H); 13 CNMR (100 MHz, CDC13) δ 193.7, 149.1, 138.1, 120.7, 118.8, 117.8, 117.0, 116.3, 51.4, 29.4.

[0084] Example 9

[0085] (1) Preparation of compound III: same as step (1) of Example 1;

[0086] (2) Preparation of compound I-i:

[0087]

[0088] In a 15 mL pressure tube, compound II-i (0.0625 g, 0.4 mmol), triruthenium dodecacarbonyl (0.0205 g, 0.032 mmol), 2-methoxyethylamine (0.030 g, 0.4 mmol), 2,4,6-trimethylbenzoic acid (0.1314 g, 0.8 mmol), cesium fluoride (0.2430 g, 1.6 mmol) were added successively, vacuumed and filled with argon, then compound III (0.1362 g, 0.8 mmol) prepared in step (1) was added successively, sealed and stirred in a magnetic heating stirrer at 130 °C for 12 hours. After the reaction was completed, the resulting reaction solution was cooled to room temperature, diluted with ethyl acetate, filtered through 300-400 mesh silica gel, eluted with ethyl acetate, concentrated under reduced pressure to remove the solvent, diluted with dichloromethane, and stirred with 200-300 mesh silica gel, dried and loaded onto a column, and separated by column chromatography (300-400 mesh silica gel, eluent: petroleum ether: ethyl acetate = 50:1, by volume) to obtain compound I-i (0.0364 g, yield 40%) as a light yellow oil.

[0089] NMR data of compound I-i: 1 H NMR (400 MHz, CDCl3) δ 10.79 (s, 1H), 10.51 (br s, 1H), 8.26 (d, J = 8.4 Hz, 1H), 7.74 (d, J = 8.8 Hz, 1H), 7.64 (dd, J = 8.0, 1.2 Hz, 1H), 7.47 (ddd, J = 8.8, 7.2, 2.0 Hz, 1H), 7.28-7.22 (m, 2H), 1.55 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 189.0, 152.0, 136.9, 136.0, 129.4, 128.8, 125.3, 122.5, 118.1, 116.0, 107.6, 51.6, 30.3.

[0090] Example 10

[0091] (1) Preparation of compound III: same as step (1) of Example 1;

[0092] (2) Preparation of compound I-j:

[0093]

[0094] In a 15 mL pressure tube, compound II-j (0.0729 g, 0.4 mmol), triruthenium dodecacarbonyl (0.0205 g, 0.032 mmol), 2-methoxyethylamine (0.030 g, 0.4 mmol), 2,4,6-trimethylbenzoic acid (0.1314 g, 0.8 mmol), cesium fluoride (0.2430 g, 1.6 mmol) were added successively, vacuumed and filled with argon, then compound III (0.1362 g, 0.8 mmol) prepared in step (1) was added successively, sealed and stirred in a magnetic heating stirrer at 130 °C for 12 hours. After the reaction was completed, the reaction solution was cooled to room temperature, diluted with ethyl acetate, filtered through 300-400 mesh silica gel, eluted with ethyl acetate, concentrated under reduced pressure to remove the solvent, diluted with dichloromethane, and stirred with 200-300 mesh silica gel, dried and loaded onto a column, and separated by column chromatography (300-400 mesh silica gel, eluent: petroleum ether: ethyl acetate = 50:1, by volume) to obtain compound I-j (0.0625 g, yield 62%) as a light yellow oil.

[0095] NMR data of compound I-j: 1 H NMR (400 MHz, CDCl3) δ 9.74 (s, 1H), 9.30 (br s, 1H), 7.42-7.37 (m, 3H), 7.36-7.31 (m, 3H), 6.95 (d, J = 8.8 Hz, 1H), 6.48 (dd, J = 7.2, 1.2 Hz, 1H), 1.50 (s, 9H); 13 C NMR (100 MHz, CDCl3) δ 194.1, 150.8, 150.0, 139.7, 134.5, 130.1, 128.2, 127.7, 116.7, 116.3, 113.0, 51.0, 29.7.

[0096] The above only describes the preferred embodiments of the present application, and it should be noted that for those skilled in the art, without departing from the technical principles of the present application, a number of improvements and modifications can be made, and these improvements and modifications should also be considered as the protection scope of the present application.

Claims

1. A method for preparing a 2-tert-butylaminobenzaldehyde derivative, characterized in that: The preparation method is, (1) N,N - Di-tert-butylurea, tert-butyl hypochlorite, potassium tert-butoxide, and triethylamine are reacted in anhydrous diethyl ether to give compound III. The structural formula of compound III is as follows: ; (2) mixing the compound III obtained in step (1) with compound II, ruthenium catalyst, amine, additive, base in a molar ratio of (2.0-2.5):1:(0.08-0.1):1:(1.5-2.0):(3.0-4.0) in a solvent, and then carrying out amination reaction at 130 DEG C under an inert atmosphere for 12 h to obtain the 2-tert-butyl aminobenzaldehyde derivative, The structural formula of the compound II is wherein, R1 represents a hydrogen atom, a methyl group, a phenyl group, a methoxy group, a fluorine atom, a chlorine atom, a methyl ester group or a cyano group; R2 represents a hydrogen atom; and R3 represents a hydrogen atom or a phenyl group, In the step (2), the ruthenium catalyst is triruthenium dodecacarbonyl; the amine is 2-methoxyethylamine; the additive is 2,4,6-trimethylbenzoic acid; and the base is cesium fluoride.

2. The method for preparing 2-tert-butylaminobenzaldehyde derivatives as described in claim 1, characterized in that: as described in step (1) N,N - Di-tert-butyl urea was obtained by mixing reaction of tert-butyl amine, triethylene diamine, di-tert-butyl dicarbonate, dichloromethane at room temperature.

3. The method for preparing 2-tert-butylaminobenzaldehyde derivatives as described in claim 1, characterized in that: In the step (2), the concentration of the compound II in the solvent is 0.2 mol / L.

4. The method for preparing 2-tert-butylaminobenzaldehyde derivatives as described in claim 1, characterized in that: In the step (2), the solvent is 1,4-dioxane or p-xylene.

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