CN117820139A - Preparation method of 2-tertiary butyl amino benzaldehyde derivative - Google Patents

Preparation method of 2-tertiary butyl amino benzaldehyde derivative Download PDF

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CN117820139A
CN117820139A CN202311846275.2A CN202311846275A CN117820139A CN 117820139 A CN117820139 A CN 117820139A CN 202311846275 A CN202311846275 A CN 202311846275A CN 117820139 A CN117820139 A CN 117820139A
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compound
mmol
derivative
tert
tertiary butyl
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刘杰灵
王建军
史一安
宏慧莹
杨鹅
张世伟
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Changzhou University
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Changzhou University
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Abstract

The invention belongs to the technical field of organic synthesis, and in particular relates to a preparation method of a 2-tertiary butyl amino benzaldehyde derivative, which comprises the steps of mixing N, N-di-tertiary butyl urea, tertiary butyl hypochloride, tertiary butyl potassium and triethylamine in anhydrous diethyl ether for reaction to obtain a compound III with the structural formula ofCombining compound III with compound II and rutheniumCatalyst, amine, additive and alkali according to (2.0-2.5): 1: (0.08-0.1): 1: (1.5-2.0): (3.0-4.0) in a solvent, and carrying out amination reaction for 10-14 h at 125-135 ℃ under an inert atmosphere to obtain the 2-tertiary butyl amino benzaldehyde derivative, wherein the structural formula of the compound II isWherein R is 1 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; r is R 2 Represents a hydrogen atom; r is R 3 Represents a hydrogen atom or a phenyl group.

Description

Preparation method of 2-tertiary butyl amino benzaldehyde derivative
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of a 2-tertiary butyl amino benzaldehyde derivative.
Background
The o-aminobenzaldehyde compound is an important organic functional group intermediate, is used as an active molecule, has important application in the fields of medicine, pesticide, organic synthesis and the like, and can be used for synthesizing nitrogen-containing heterocyclic compounds such as quinoline, derivatives thereof and the like. Therefore, the synthesis of anthranilaldehyde derivatives is highly valued by the masses of chemists. The reduction reaction of the o-nitrobenzaldehyde derivatives is one of the main methods for preparing the o-aminobenzaldehyde derivatives, but has the defects of severe reaction conditions, multiple side reactions and the like.
Disclosure of Invention
In order to solve the technical problems, the invention provides a preparation method of a 2-tertiary butyl amino benzaldehyde derivative, which has the advantages of simple operation, less side reaction and excellent yield, and can directly prepare a series of 2-tertiary butyl amino benzaldehyde derivatives through ortho-C-H amination of benzaldehyde:
(1) Mixing N, N-di-tert-butyl urea, tert-butyl hypochlorite, potassium tert-butoxide and triethylamine in anhydrous diethyl ether to obtain a compound III with a structural formula of
(2) Mixing the compound III obtained in the step (1) with the compound II, a ruthenium catalyst, amine, an additive and alkali in a solvent, performing amination reaction in an inert atmosphere to obtain a 2-tertiary butyl amino benzaldehyde derivative,
the structural formula of the compound II isWherein R is 1 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; r is R 2 Represents a hydrogen atom; r is R 3 Represents a hydrogen atom or a phenyl group,
the synthesis reaction formula is as follows:
as preferable: the N, N-di-tert-butyl urea in the step (1) is obtained by mixing and reacting tert-butylamine, triethylene diamine, di-tert-butyl dicarbonate and methylene dichloride at room temperature (25 ℃ C., the same as the above).
As preferable: in the step (2), the molar ratio of the compound II to the ruthenium catalyst to the amine to the additive to the alkali to the compound III is 1: (0.08-0.1): 1: (1.5-2.0): (3.0-4.0): (2.0-2.5).
As preferable: in step (2), the concentration of compound II in the solvent was 0.2 mol/liter.
As preferable: the ruthenium catalyst in the step (2) is triruthenium dodecacarbonyl.
As preferable: the amine in step (2) is 2-methoxyethylamine.
As preferable: the additive in the step (2) is 2,4, 6-trimethyl benzoic acid.
As preferable: the base in step (2) is cesium fluoride.
As preferable: the solvent in the step (2) is 1, 4-dioxane or paraxylene.
As preferable: in the step (2), the reaction temperature of the amination reaction is 125-135 ℃ and the reaction time is 10-14 h.
The specific synthesis mechanism of the scheme is as follows:
condensing a substrate compound II with 2-methoxyethylamine to generate imine 1, complexing the imine 1 with a ruthenium catalyst, activating the imine with hydrocarbon to generate an ortho-activated ruthenium ring intermediate 3, oxidizing and adding the ortho-activated ruthenium ring intermediate 3 with a ternary ring nitrogen-containing reagent compound III to generate a corresponding ruthenium intermediate 4, releasing tBuNCO to obtain a nitrene intermediate 5, reducing and eliminating the nitrene intermediate 5 to obtain an aminated product 7 and the ruthenium catalyst, and carrying out acidic hydrolysis on the aminated product 7 by a silica gel column to generate a corresponding aminated product I; wherein the methoxyimine has the function of a guiding group.
In the preparation method, the initial substrate benzaldehyde compound II is simple and easy to obtain, the substrate range is wide, the synthesis operation is simple, the side reaction is few, the yield is excellent, the substitution of specific functional groups on the carbon position to be reacted is not needed, the aryl C-H bond can be directly aminated, and the 2-tertiary butyl amino benzaldehyde derivative with various substituent groups can be synthesized.
The N, N-di-tert-butyl diazacyclo-ketone is used as a nitrogen source, the prepared 2-tert-butylamino benzaldehyde derivative contains N-tert-butyl, the N-tert-butyl is easy to remove, and the N-tert-butylamino benzaldehyde derivative can be used as a protecting group in aromatic amine nitrogen, and has a good protecting effect in the further derivatization reaction of the 2-tert-butylamino benzaldehyde derivative.
Detailed Description
The reagents used in the examples below were all commercially available, with the tricarbonyl triruthenium and 2-methoxyethylamine from the Pickle reagent, 2,4, 6-trimethylbenzoic acid from the Legend reagent, and cesium fluoride from 3 ACchemical.
Example 1
(1) Preparation of Compound III:
tert-butylamine (52.5 mL,500.0 mmol), triethylenediamine (DABCO) (5.6 g,250.0 mmol) and methylene dichloride (200.0 mL) are added into a reactor, di-tert-butyl dicarbonate (57.5 mL,50.0 mmol) is dissolved into methylene dichloride (50.0 mL) and is added into the reactor, the mixture is stirred at room temperature for reaction for 12h, after the reaction, the reaction solution in the reactor is cooled to 0 ℃,250 mL of N-hexane is added into the reaction solution to better precipitate and separate out a target product, and then the reaction solution is filtered, and filter cakes are washed by supercooled water and diethyl ether in sequence to obtain white solid N, N-di-tert-butyl urea.
N, N-Di-t-butylurea (20.0 g,116.1 mmol) prepared as described above, diethyl ether were charged into another reactor
(200.0 mL), then tert-butyl hypochlorite (13.9 mL,127.7 mmol) was added dropwise thereto, triethylamine (0.16 mL,2 mmol) was further added thereto, after stirring at room temperature for 30 minutes, the reaction solution in the reactor was cooled to 5℃and then potassium tert-butoxide (17.0 g,150.9 mmol) was slowly added thereto, after naturally warming to room temperature and then stirring for 12 hours, 150mL of n-hexane was added to the obtained reaction solution, washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered, dried by spin-drying, distilled under reduced pressure to obtain Compound III as a colorless liquid, (11.6 g, yield 59%),
nuclear magnetic data of compound iii: 1 H NMR(400MHz,CDCl 3 ):δ1.30(s,18H)； 13 C NMR(100MHz,CDCl 3 ):δ158.8,59.1,26.8。
(2) Preparation of Compound I-a:
a15 mL pressure-resistant tube was charged with 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), and then with argon gas, an ultra-dry 1, 4-dioxane (2.0 mL) and compound III (0.1362 g,0.8 mmol) produced in step (1) were sequentially charged, and the mixture was stirred in a magnetic stirrer at 130℃for 12 hours, after the reaction was completed, the mixture was cooled to room temperature, the resultant reaction mixture was diluted in ethyl acetate, and then filtered through 300 to 400 mesh silica gel, the ethyl acetate was eluted (the ternary ring of the excess compound III which did not participate in the synthesis reaction was degraded in the above reaction to form urea in the course of time, and the urea was eluted with ethyl acetate having a large polarity), the same solvent as that was eluted with the ultra-dry 1, 4-dioxane (2.0 mL) was charged, 0.1362g,0.8 mmol), and the mixture was separated by a dry column chromatography, and a 200-300 mesh eluent was separated by using a dry column chromatography, and a diluted solution was used as a 200-300 mesh eluent; ethyl acetate=50:1 (volume ratio), because the eluent mainly composed of petroleum ether has significantly smaller polarity, the urea cannot be eluted together, and separation from the target product is achieved, as described below, to give compound I-a (0.0305 g, yield 43%) as pale yellow solid.
Nuclear magnetic data of compound I-a: 1 H NMR(400MHz,CDCl 3 )δ9.77(s,1H),8.65(br s,1H),7.43(dd,J＝8.0,2.0Hz,1H),7.33(ddd,J＝8.8,6.8,1.6Hz,1H),6.91(d,J＝8.8Hz,1H),6.64(t,J＝7.6Hz,1H),1.46(s,9H)； 13 C NMR(100MHz,CDCl 3 )δ194.0,150.2,137.7,135.1,119.0,114.2,113.3,50.9,29.6。
comparative example 1
The catalyst used in step (2) was replaced by "ruthenium chloride", and the rest was the same as in example 1:
(1) Preparation of Compound III: step (1) is the same as in example 1;
(2) 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 sequentially added to a 15mL pressure-resistant tube, argon was introduced under vacuum, then ultra-dry 1, 4-dioxane (2.0 mL) and compound III (0.1362 g,0.8 mmol) produced in step (1) were sequentially added, the mixture was stirred in a magnetic stirrer at 130℃for reaction for 12 hours, after the reaction was completed, the mixture was cooled to room temperature, the obtained reaction mixture was added to ethyl acetate for dilution, then filtered through 300-400 mesh silica gel, ethyl acetate was eluted, and concentrated under reduced pressure to remove the solvent, diluted with 200-300 mesh silica gel, the dry sample was applied, and separated by a 300-400 mesh silica gel column chromatography (eluent: ethyl acetate: 50 vol.), the solid product was obtained as a pale yellow solid product was analyzed as 6.8 mg, and the solid product was obtained as a 1.6 mg, after the solid product was analyzed as a solid product was analyzed as 6 mg.
Comparative example 2
The procedure of example 1 is followed except that the catalyst used in step (2) is replaced by "palladium bromide":
(1) Preparation of Compound III: step (1) is the same as in example 1;
(2) In a 15mL pressure-resistant 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 sequentially added, argon was introduced by vacuum, then ultra-dry 1, 4-dioxane (2.0 mL) and compound III (0.1362 g,0.8 mmol) produced in step (1) were sequentially added, and the mixture was stirred in a magnetic stirrer at 130℃for 12 hours in a sealed manner, after the reaction was completed, cooled to room temperature, the obtained reaction mixture was diluted in ethyl acetate, filtered through 300 to 400 mesh silica gel, eluted with ethyl acetate, concentrated under reduced pressure to remove the solvent, diluted with 200 to 300 mesh silica gel, and subjected to dry loading, and after separation by 300 to 400 mesh silica gel column chromatography (eluent: ethyl acetate: 50: volume: 1: no product was found to exist).
As can be seen from comparative example 1 and comparative example 2: in the application, the imine condensed by the 2-methoxyethylamine and the benzaldehyde is used for guiding the synthesis reaction with the three-membered ring nitrogen source compound III, the palladium metal catalyst cannot realize the catalysis smoothly, the catalytic effect of the common ruthenium metal salt is very low when the ruthenium metal catalyst is used, and the catalytic generated products are very few, and the effective catalytic effect can be obtained only when the ruthenium carbon oxide is used as the catalyst in the scheme.
Example 2
(1) Preparation of Compound III: step (1) is the same as in example 1;
(2) Preparation of Compound I-b:
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 to a 15mL pressure-resistant tube, argon was introduced under vacuum, then ultra-dry 1, 4-dioxane (2.0 mL) and compound III (0.1362 g,0.8 mmol) produced in step (1) were sequentially added, the mixture was stirred in a magnetic stirrer at 130℃for 12 hours, after the reaction was completed, the mixture was cooled to room temperature, the obtained reaction mixture was added to ethyl acetate for dilution, and then filtered through 300 to 400 mesh silica gel, ethyl acetate was eluted, concentrated under reduced pressure to remove the solvent, and then diluted with 200 to 300 mesh silica gel, and the mixture was dried and separated by a 300 to 400 mesh column chromatography (eluent: ethyl acetate: 50 vol: 1: volume%) to obtain a pale yellow oil, I-030, which was obtained as a yellow oil (39: 0.030%).
Nuclear magnetic data of compound I-b: 1 H NMR(400MHz,CDCl 3 )δ9.70(s,1H),8.64(br s,1H),7.31(d,J＝8.0Hz,1H),6.70(d,J＝1.6Hz,1H),6.46(dd,J＝8.0,1.6Hz,1H),2.33(s,3H),1.46(s,9H)； 13 C NMR(100MHz,CDCl 3 ) Delta 193.2,150.3,146.3,137.7,117.2,115.8,113.5,50.9,29.6,22.8 example 3
(1) Preparation of Compound III: step (1) is the same as in example 1;
(2) Preparation of Compound I-c:
compound II-c (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 sequentially added to a 15mL pressure-resistant tube, argon was introduced under vacuum, then ultra-dry 1, 4-dioxane (2.0 mL) and compound III (0.1362 g,0.8 mmol) produced in step (1) were sequentially added, the mixture was stirred in a magnetic stirrer at 130℃for 12 hours, after the reaction was completed, the mixture was cooled to room temperature, the obtained reaction mixture was added to ethyl acetate for dilution, and then was subjected to 300-400 mesh silica gel filtration, ethyl acetate elution, concentration was performed to remove the solvent, and then 200-300 mesh silica gel was used for dilution, and a dry method was used for separation by silica gel column chromatography (eluent: 50: ethyl acetate: volume: 1:67% to obtain a pale yellow oil, I) as a yellow oil, and a ratio of 67.67% of the compound I was obtained (67%).
Nuclear magnetic data for compounds I-c: 1 H NMR(400MHz,CDCl 3 )δ9.81(s,1H),8.73(br s,1H),7.65-7.58(m,2H),7.52-7.39(m,4H),7.10(d,J＝1.6Hz,1H),6.87(dd,J＝8.0,1.6Hz,1H),1.52(s,9H)； 13 C NMR(100MHz,CDCl 3 )δ193.5,150.3,147.8,141.1,138.1,129.0,128.4,127.5,118.1,113.7,111.9,51.0,29.7.
example 4
(1) Preparation of Compound III: step (1) is the same as in example 1;
(2) Preparation of Compounds I-d:
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 sequentially added to a 15mL pressure-resistant tube, argon was introduced under vacuum, then ultra-dry 1, 4-dioxane (2.0 mL) and compound III (0.1362 g,0.8 mmol) produced in step (1) were sequentially added, the mixture was stirred in a magnetic stirrer at 130℃for 12 hours, after the reaction was completed, the mixture was cooled to room temperature, the obtained reaction mixture was added to ethyl acetate for dilution, and then filtered through 300 to 400 mesh silica gel, ethyl acetate was eluted, concentrated under reduced pressure to remove the solvent, and then diluted with 200 to 300 mesh silica gel, and the mixture was dried and separated by a 300 to 400 mesh column chromatography (eluent: 50% ethyl acetate: volume: 1: 0.035% to yield pale yellow oil, I) was obtained as a yellow oil (0.035% by volume).
Nuclear magnetic data for compounds I-d: 1 H NMR(400MHz,CDCl 3 )δ9.60(s,1H),8.78(br s,1H),7.32(d,J＝8.8Hz,1H),6.30(d,J＝2.4Hz,1H),6.22(dd,J＝8.8,2.4Hz,1H),3.84(s,3H),1.46(s,9H)； 13 C NMR(100MHz,CDCl 3 ) Delta 191.8,165.1,151.9,139.8,114.3,102.1,96.9,55.4,50.8,29.4 example 5
(1) Preparation of Compound III: step (1) is the same as in example 1;
(2) Preparation of Compound I-e:
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 sequentially added to a 15mL pressure-resistant tube, argon was introduced under vacuum, then ultra-dry 1, 4-dioxane (2.0 mL) and compound III (0.1362 g,0.8 mmol) produced in step (1) were sequentially added, the mixture was stirred in a magnetic stirrer at 130℃for 12 hours, after the reaction was completed, the mixture was cooled to room temperature, the obtained reaction mixture was added to ethyl acetate for dilution, and then filtered through 300 to 400 mesh silica gel, ethyl acetate was eluted, concentrated under reduced pressure to remove the solvent, and then diluted with 200 to 300 mesh silica gel, and the mixture was dried and separated by a 300 to 400 mesh column chromatography (eluent: 50 vol: 1: 50 vol%) of ethyl acetate, and a pale yellow oil I (47%) was obtained as a pale yellow oil, I: 47%).
Nuclear magnetic data for compounds I-e: 1 H NMR(400MHz,CDCl 3 )δ9.69(s,1H),8.86(br s,1H),7.41(dd,J＝8.8,6.8Hz,1H),6.53(dd,J＝12.8,2.4Hz,1H),6.33(td,J＝8.0,2.4Hz,1H),1.45(s,9H)； 13 C NMR(100MHz,CDCl 3 )δ192.6,167.4(d,J＝251.5Hz),152.0(d,J＝13.6Hz),140.5(d,J＝13.2Hz),116.4,102.6(d,J＝23.7Hz),99.4(d,J＝26.3Hz),51.2,29.3.
example 6
(1) Preparation of Compound III: step (1) is the same as in example 1;
(2) Preparation of Compounds I-f:
compounds 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 sequentially added to a 15mL pressure-resistant tube, argon was introduced under vacuum, then ultra-dry 1, 4-dioxane (2.0 mL) and compound III (0.1362 g,0.8 mmol) produced in step (1) were sequentially added, the mixture was stirred in a magnetic stirrer at 130℃for 12 hours, after the reaction was completed, the mixture was cooled to room temperature, the obtained reaction mixture was added to ethyl acetate for dilution, and then filtered through 300 to 400 mesh silica gel, ethyl acetate was eluted, concentrated under reduced pressure to remove the solvent, and then diluted with 200 to 300 mesh silica gel, and the mixture was dried and separated by a 300 to 400 mesh column chromatography (eluent: ethyl acetate: 50 vol.: 1.6 g) in the form of yellow oil, and the mixture was obtained as a pale yellow oil (0.040 6 g: 48%).
Nuclear magnetic data for compounds I-f: 1 H NMR(400MHz,CDCl 3 )δ9.71(s,1H),8.74(br s,1H),7.34(d,J＝8.4Hz,1H),6.87(d,J＝1.6Hz,1H),6.60(dd,J＝8.4,2.0Hz,1H),1.45(s,9H)； 13 C NMR(100MHz,CDCl 3 )δ193.0,150.5,141.8,138.9,117.6,114.8,112.9,51.2,29.4.
example 7
(1) Preparation of Compound III: step (1) is the same as in example 1;
(2) Preparation of Compound I-g:
in a 15mL pressure-resistant tube, sequentially added were the compound II-g (0.0657 g,0.4 mmol), the tricarbonyl ruthenium (0.0205 g,0.032 mmol), the 2-methoxyethylamine (0.030 g,0.4 mmol), the 2,4, 6-trimethylbenzoic acid (0.1314 g,0.8 mmol), cesium fluoride (0.2430 g,1.6 mmol), and argon gas, then the ultra-dry 1, 4-dioxane (2.0 mL) and the compound III (0.1362 g,0.8 mmol) produced in the step (1), were placed in a magnetic heating stirrer in this order, stirred at 130℃for 12 hours, after the reaction was completed, cooled to room temperature, the obtained reaction solution was added to ethyl acetate for dilution, filtered through 300 to 400 mesh silica gel, eluted with ethyl acetate, concentrated under reduced pressure to remove the solvent, diluted with 200 to 300 mesh silica gel, and dried and separated by a 300 to 400 mesh column chromatography (eluent: ethyl acetate: 50 vol.: 1.39 vol.%), and the compound I was obtained as a pale yellow oil (39:39%).
Nuclear magnetic data for compounds I-g: 1 H NMR(400MHz,CDCl 3 )δ9.85(s,1H),8.64(br s,1H),7.60(d,J＝1.6Hz,1H),7.50(d,J＝8.0Hz,1H),7.23(dd,J＝8.4,1.6Hz,1H),3.92(s,3H),1.48(s,9H)； 13 C NMR(100MHz,CDCl 3 )δ194.0,166.9,149.6,137.6,135.3,121.0,114.9,114.3,52.6,51.2,29.6.
example 8
(1) Preparation of Compound III: step (1) is the same as in example 1;
(2) Preparation of Compound I-h:
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 sequentially added to a 15mL pressure-resistant tube, argon was introduced under vacuum, then ultra-dry 1, 4-dioxane (2.0 mL) and compound III (0.1362 g,0.8 mmol) produced in step (1) were sequentially added, the mixture was stirred in a magnetic stirrer at 130℃for 12 hours, after the reaction was completed, the mixture was cooled to room temperature, the obtained reaction mixture was added to ethyl acetate for dilution, and then filtered through 300 to 400 mesh silica gel, ethyl acetate was eluted, concentrated under reduced pressure to remove the solvent, and then diluted with 200 to 300 mesh silica gel, and the mixture was dried and separated by a 300 to 400 mesh column chromatography (eluent: ethyl acetate: 50 vol: 1: volume%) to obtain a pale yellow oil I (37%) in the form of a pale yellow oil, the mixture was obtained by the following the reaction of which was prepared in the steps of (37%).
Nuclear magnetic data for compounds I-h: 1 H NMR(400MHz,CDCl 3 )δ9.82(s,1H),8.74(br s,1H),7.52(d,J＝8.0Hz,1H),7.14(d,J＝1.6Hz,1H),6.85(dd,J＝7.6,1.2Hz,1H),1.46(s,9H)； 13 C NMR(100MHz,CDCl 3 )δ193.7,149.1,138.1,120.7,118.8,117.8,117.0,116.3,51.4,29.4.
example 9
(1) Preparation of Compound III: step (1) is the same as in example 1;
(2) Preparation of Compound I-I:
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 sequentially added to a 15mL pressure-resistant tube, argon was introduced under vacuum, then ultra-dry 1, 4-dioxane (2.0 mL) and compound III (0.1362 g,0.8 mmol) produced in step (1) were sequentially added, the mixture was stirred in a magnetic stirrer at 130℃for 12 hours, after the reaction was completed, the mixture was cooled to room temperature, the obtained reaction mixture was added to ethyl acetate for dilution, and then filtered through 300 to 400 mesh silica gel, ethyl acetate was eluted, concentrated under reduced pressure to remove the solvent, and then diluted with 200 to 300 mesh silica gel, and the mixture was dried and separated by a 300 to 400 mesh column chromatography (eluent: 50 vol: ethyl acetate: volume: 40% to obtain a pale yellow oil, I) in the form of a yellow oil (40%).
Nuclear magnetic data for compound I-I: 1 H NMR(400MHz,CDCl 3 )δ10.79(s,1H),10.51(br s,1H),8.26(d,J＝8.4Hz,1H),7.74(d,J＝8.8Hz,1H),7.64(dd,J＝8.0,1.2Hz,1H),7.47(ddd,J＝8.8,7.2,2.0Hz,1H),7.28-7.22(m,2H),1.55(s,9H)； 13 C NMR(100MHz,CDCl 3 )δ189.0,152.0,136.9,136.0,129.4,128.8,125.3,122.5,118.1,116.0,107.6,51.6,30.3.
example 10
(1) Preparation of Compound III: step (1) is the same as in example 1;
(2) Preparation of Compound I-j:
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 sequentially added to a 15mL pressure-resistant tube, argon was introduced under vacuum, then ultra-dry 1, 4-dioxane (2.0 mL) and compound III (0.1362 g,0.8 mmol) produced in step (1) were sequentially added, the mixture was stirred in a magnetic heating stirrer at 130℃for 12 hours, after the reaction was completed, the mixture was cooled to room temperature, the obtained reaction mixture was added to ethyl acetate for dilution, and then filtered through 300 to 400 mesh silica gel, ethyl acetate was eluted, concentrated under reduced pressure to remove the solvent, and then diluted with 200 to 300 mesh silica gel, and the mixture was applied by a dry method, and separated by a 300 to 400 mesh silica gel column chromatography (eluent: ethyl acetate: 50 vol: 1: volume: 62% to obtain a pale yellow oil, I) as a pale yellow oil, I (0.5 g: j) was obtained as a pale yellow oil, I).
Nuclear magnetic data of compound I-j: 1 H NMR(400MHz,CDCl 3 )δ9.74(s,1H),9.30(br s,1H),7.42-7.37(m,3H),7.36-7.31(m,3H),6.95(d,J＝8.8Hz,1H),6.48(dd,J＝7.2,1.2Hz,1H),1.50(s,9H)； 13 C NMR(100MHz,CDCl 3 )δ194.1,150.8,150.0,139.7,134.5,130.1,128.2,127.7,116.7,116.3,113.0,51.0,29.7.
the foregoing is merely a preferred embodiment of the present invention, and it should be noted that modifications and variations could be made by those skilled in the art without departing from the technical principles of the present invention, and such modifications and variations should also be regarded as being within the scope of the invention.

Claims (8)

1. A preparation method of a 2-tertiary butyl amino benzaldehyde derivative is characterized by comprising the following steps of: the preparation method is that,
(1) Mixing N, N-di-tert-butyl urea, tert-butyl hypochlorite, potassium tert-butoxide and triethylamine in anhydrous diethyl ether to react to obtain a compound III, wherein the structural formula of the compound III is
(2) And (2) mixing the compound III obtained in the step (1) with a compound II, a ruthenium catalyst, amine, an additive and alkali according to the following proportion (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 for 10-14 h at 125-135 ℃ in an inert atmosphere to obtain the 2-tertiary butyl amino benzaldehyde derivative,
the structural formula of the compound II isWherein R is 1 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; r is R 2 Represents a hydrogen atom; r is R 3 Represents a hydrogen atom or a phenyl group.
2. The process for producing a 2-t-butylaminobenzaldehyde derivative as claimed in claim 1, wherein: the N, N-di-tert-butyl urea in the step (1) is obtained by mixing tert-butylamine, triethylene diamine, di-tert-butyl dicarbonate and methylene dichloride at room temperature.
3. The process for producing a 2-t-butylaminobenzaldehyde derivative as claimed in claim 1, wherein: in step (2), the concentration of the compound II in the solvent is 0.2 mol/liter.
4. The process for producing a 2-t-butylaminobenzaldehyde derivative as claimed in claim 1, wherein: the ruthenium catalyst in the step (2) is triruthenium dodecacarbonyl.
5. The process for producing a 2-t-butylaminobenzaldehyde derivative as claimed in claim 1, wherein: the amine in the step (2) is 2-methoxyethylamine.
6. The process for producing a 2-t-butylaminobenzaldehyde derivative as claimed in claim 1, wherein: the additive in the step (2) is 2,4, 6-trimethyl benzoic acid.
7. The process for producing a 2-t-butylaminobenzaldehyde derivative as claimed in claim 1, wherein: the base in the step (2) is cesium fluoride.
8. The process for producing a 2-t-butylaminobenzaldehyde derivative as claimed in claim 1, wherein: the solvent in the step (2) is 1, 4-dioxane or paraxylene.
CN202311846275.2A 2023-12-29 2023-12-29 Preparation method of 2-tertiary butyl amino benzaldehyde derivative Pending CN117820139A (en)

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