阅读说明：本技术 一种催化亚胺还原成胺的合成方法 (Synthesis method for catalyzing reduction of imine into amine ) 是由 温慧玲 罗人仕 罗年华 于 2020-12-21 设计创作，主要内容包括：本发明公开了一种催化亚胺还原成胺的合成方法,其特征在于,该方法包括以下步骤:步骤1：常温常压下,按照反应摩尔比为1:0.01依次将磺酰亚胺类化合物和催化剂I置于反应瓶中,再按照体积比5:2加入甲酸和三乙胺溶液,在溶剂中反应1～15min,得到反应产物；步骤2：步骤1反应结束后,向得到的反应产物中依次缓慢加入水和乙酸乙酯,充分搅拌后静置分层,分出的水层用乙酸乙酯萃取,将乙酸乙酯的萃取物与分出的有机层合并后,分别用饱和食盐水洗涤、无水硫酸钠干燥,蒸除乙酸乙酯溶剂后得到粗产物,然后经硅胶柱层析分离纯化得到胺类化合物。(The invention discloses a synthesis method for catalyzing reduction of imine into amine, which is characterized by comprising the following steps of: placing a sulfimide compound and a catalyst I into a reaction bottle in sequence according to a reaction molar ratio of 1:0.01 at normal temperature and normal pressure, adding a formic acid and triethylamine solution according to a volume ratio of 5:2, and reacting in a solvent for 1-15 min to obtain a reaction product; step 2: after the reaction in the step 1 is finished, water and ethyl acetate are sequentially and slowly added into the obtained reaction product, the mixture is fully stirred and then is kept stand for layering, the separated water layer is extracted by ethyl acetate, the ethyl acetate extract and the separated organic layer are combined, then the mixture is respectively washed by saturated saline solution and dried by anhydrous sodium sulfate, a crude product is obtained after the ethyl acetate solvent is removed by evaporation, and then the amine compound is obtained by silica gel column chromatography separation and purification.)

1. A method of synthesizing an amine by catalytic reduction of an imine, the method comprising the steps of:

step 1: placing a sulfimide compound and a catalyst I in a reaction bottle in sequence at normal temperature and normal pressure, then adding formic acid and triethylamine solution, adding water as a solvent, and reacting for 1-15 min to obtain a reaction product;

step 2: after the reaction in the step 1 is finished, water and ethyl acetate are sequentially and slowly added into the obtained reaction product, the mixture is fully stirred and then is kept stand for layering, the separated water layer is extracted by ethyl acetate, the ethyl acetate extract and the separated organic layer are combined, then the mixture is respectively washed by saturated saline solution and dried by anhydrous sodium sulfate, a crude product is obtained after the ethyl acetate solvent is removed by evaporation, and then the amine compound is obtained by silica gel column chromatography separation and purification.

2. A synthesis method for catalyzing the reduction of imine to amine according to claim 1, wherein in step 1, the mass molar ratio of the sulfonamide compound to catalyst I is 1: 0.01.

3. The method as claimed in claim 1, wherein the volume ratio of formic acid to triethylamine solution in step 1 is 5: 2.

4. The method as claimed in claim 1, wherein in step 1, the catalyst I is a catalyst formed by coordination of a chiral amide ligand and iridium metal.

5. A synthesis method for catalyzing the reduction of imine to amine according to claim 4, wherein the coordination of chiral amide ligand with iridium metal to form catalyst comprises the following steps:

(1) at room temperature, (2S, 3aS, 7aS) -octahydro-1H-indole-2-carboxylic acid (1-1), di-tert-butyl dibasic acid and triethylamine are sequentially added in a reaction molar ratio of 1:1.1:1.1, stirred in a dichloromethane solution overnight until complete conversion, and then a citric acid solution is used for adjusting the pH value of a reaction mixture to 7-8; separating organic layer, extracting inorganic layer with dichloromethane for 3-5 times, washing combined organic layer with brine, drying with anhydrous sodium sulfate, and concentrating to obtain compound 2-1 for use in next step;

(2) dropwise adding 1.2 equivalents of ethyl carbo-chloride into a dichloromethane solution of a compound 2-1 and triethylamine, stirring at 0 ℃ for 1 hour, then continuously adding 1.2 equivalents of amine, stirring the reaction mixture overnight, adjusting the pH value to 7-9 by using a citric acid solution and saturated sodium carbonate, washing with brine, drying an organic layer on anhydrous sodium sulfate, and concentrating to obtain a compound 3-1;

(3) to a dichloromethane solution of 3 to 11.0 equivalents of the compound was added trifluoroacetic acid 20.0 equivalents, the solution was stirred until complete conversion, and then saturated Na was added₂CO₃The reaction was neutralized to pH 9 and the aqueous layer was extracted with dichloromethane and the combined organic layers were washed with brine, washed with Na₂SO₄Drying and concentrating to obtain amides A-C which are respectively a compound A, a compound B and a compound C;

(4) reacting [ IrCp Cl₂]₂Mixing 1.0 equivalent with corresponding 2.0 equivalents of amide A-C, synthesizing catalysts Cat-1-Cat-3 at room temperature, stirring overnight, evaporating the yellow solution to obtain yellow solid, and obtaining the catalyst I which can be directly used for reduction of imine.

6. A synthesis process for the catalytic reduction of an imine to an amine according to claim 5, wherein the molar ratio of compound 2-1 to triethylamine is 1: 1.1.

Technical Field

The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method for catalyzing reduction of imine into amine.

Background

Amine substances are organic substances widely existing in nature and are commonly used in industry, agriculture and pharmaceutical industry. For example, sulfonamides are a well-known class of compounds having antibacterial activity. Also, aprevir, which acts as a fifth generation antiretroviral protease inhibitor, by blocking the formation process of new, mature virions released from the surface of infected host cells, inhibiting viral proteases, and the like.

In recent years, the synthesis of sulfonamides has become a focus of recent research. Chemists are still striving to develop efficient and environmentally friendly syntheses of amines or sulfonamides. The prior methods for synthesizing sulfanilamide compounds comprise the following steps:

1. aldehydes or ketones and amines (such as sulfanilamide) are used in the reaction of HCOOH and HCOONa at pH 4.8, and are reduced in situ to form amines or sulfonamides when heated to 80 deg.C. The disadvantages of this condition are longer reaction time, higher and lower yield, which is affected by the structure of the substrate, and different yield from 44% to 99%. Meanwhile, the conditions have high requirements on the pH, and meanwhile, heating is required, so that the operation requirements are strict.

2. Imines by reducing agents, e.g. LiAlH₄And NaBH4, but the reducing agents such as LiAlH4 and NaBH4 have poor safety, higher experimental operation requirements and difficult process amplification.

3. Hydrogenation reduction with H under a certain atmospheric pressure₂The imine is directly reduced to quickly obtain the amine compound. However, this method requires the use of H under a certain atmospheric pressure₂The safety of the operation is poor.

4. Organic molecule catalysis. Amine compounds are produced by imine hydrogenation catalyzed by ion pairs formed from organic molecules such as thiourea molecules, iodine molecules, or bronsted acids, or lewis acids and bases, using hans' esters, or cyclohexene-1, 4-diene, or silane hydrogen as the hydrogen source.

5. Metal catalysis. The principle of bifunctional catalysis of metal and complexing agent makes metal catalysis a hot spot of research in the catalytic field in recent years. There are many metals that can achieve reduction of imine, such as Ir, Rh, Ru, Ti, Ni, Au, Se, Cu, Mn, Co, Fe, Mo. Al, and the like. Although the above-mentioned metals can reduce the imine, the conditions are generally in a nonaqueous solvent, heating is often required, and the reaction time is relatively long.

Disclosure of Invention

Aiming at the technical problems, the invention designs and synthesizes a chiral ligand containing amide, and the chiral ligand and metal Ir form a coordination compound which is used as a catalyst for imine reduction, and the method can be realized under the conditions of water as a solvent, no pressurization, no nitrogen protection and normal temperature.

The technical scheme adopted by the invention is as follows:

a method of synthesizing an amine by catalytic reduction of an imine, the method comprising the steps of:

step 1: placing a sulfimide compound and a catalyst I in a reaction bottle in sequence at normal temperature and normal pressure, then adding formic acid and triethylamine solution, adding water as a solvent, and reacting for 1-15 min to obtain a reaction product;

step 2: after the reaction in the step 1 is finished, water and ethyl acetate are sequentially and slowly added into the obtained reaction product, the mixture is fully stirred and then is kept stand for layering, the separated water layer is extracted by ethyl acetate, the ethyl acetate extract and the separated organic layer are combined, then the mixture is respectively washed by saturated saline solution and dried by anhydrous sodium sulfate, a crude product is obtained after the ethyl acetate solvent is removed by evaporation, and then the amine compound is obtained by silica gel column chromatography separation and purification.

Preferably, in the step 1, the mass molar ratio of the sulfonamide compound to the catalyst I is 1: 0.01.

Preferably, in the step 1, the volume ratio of the formic acid to the triethylamine solution is 5: 2.

Preferably, in the step 1, the catalyst I is formed by coordination of chiral amide ligand and metallic iridium.

Preferably, the process of coordinating the chiral amide ligand with iridium metal to form the catalyst comprises the steps of:

(1) at room temperature, (2S, 3aS, 7aS) -octahydro-1H-indole-2-carboxylic acid (1-1), di-tert-butyl dibasic acid and triethylamine are sequentially added in a reaction molar ratio of 1:1.1:1.1, stirred in a dichloromethane solution overnight until complete conversion, and then a citric acid solution is used for adjusting the pH value of a reaction mixture to 7-8; separating organic layer, extracting inorganic layer with dichloromethane for 3-5 times, washing combined organic layer with brine, drying with anhydrous sodium sulfate, and concentrating to obtain compound 2-1 for use in next step;

(2) dropwise adding 1.2 equivalents of ethyl carbo-chloride into a dichloromethane solution of a compound 2-1 and triethylamine, stirring at 0 ℃ for 1 hour, then continuously adding 1.2 equivalents of amine, stirring the reaction mixture overnight, adjusting the pH value to 7-9 by using a citric acid solution and saturated sodium carbonate, washing with brine, drying an organic layer on anhydrous sodium sulfate, and concentrating to obtain a compound 3-1;

(3) to a dichloromethane solution of 3 to 11.0 equivalents of the compound was added trifluoroacetic acid 20.0 equivalents, the solution was stirred until complete conversion, and then saturated Na was added₂CO₃The reaction was neutralized to pH 9 and the aqueous layer was extracted with dichloromethane and the combined organic layers were washed with brine, washed with Na₂SO₄Drying and concentrating to obtain amides A-C which are respectively a compound A, a compound B and a compound C;

(4) reacting [ IrCp Cl₂]₂Mixing 1.0 equivalent with corresponding 2.0 equivalents of amide A-C, synthesizing catalysts Cat-1-Cat-3 at room temperature, stirring overnight, evaporating the yellow solution to obtain yellow solid, and obtaining the catalyst I which can be directly used for reduction of imine.

Preferably, the molar ratio of compound 2-1 to triethylamine is 1: 1.1.

The invention has the beneficial effects that:

1. the invention adopts chiral amide ligand and metallic iridium to coordinate to form the catalyst, and can realize reduction of imine at room temperature within 5min under the condition of taking water as a solvent.

2. The substrate has wide application range, and the catalyst can realize the reduction of imine with different substituents on N and carbon.

3. The invention has high catalytic efficiency and small catalyst dosage, and can obtain products in a short time.

4. The method has the advantages of simple operation, wide applicability, low cost, environmental friendliness and the like, and has very good industrial application prospect.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the drawings without creative efforts.

FIG. 1 is a drawing of Compound A¹H spectrum; FIG. 2 is a drawing of Compound A¹³C spectrum;

FIG. 3 is a drawing of Compound B¹H spectrum; FIG. 4 is a drawing of Compound B¹³C spectrum;

FIG. 5 is a drawing of Compound C¹H spectrum; FIG. 6 is a drawing of Compound C¹³C spectrum;

FIG. 7 shows a schematic representation of catalyst-1¹H spectrum; FIG. 8 shows catalyst-1¹³C spectrum;

FIG. 9 shows the method of preparing catalyst-2¹H spectrum; FIG. 10 shows catalyst-2¹³C spectrum;

FIG. 11 shows the product (2aa)¹H spectrum; FIG. 12 shows the product (2aa)¹³C spectrum;

FIG. 13 shows the product (2ab)¹H spectrum; FIG. 14 shows the product (2ab)¹³C spectrum;

FIG. 15 is of product (2ac)¹H spectrum; FIG. 16 is of product (2ac)¹³C spectrum;

FIG. 17 shows the product (2ad)¹H spectrum; FIG. 18 shows the product (2ad)¹³C spectrum;

FIG. 19 is of product (2ae)¹H spectrum; FIG. 20 is of product (2ae)¹³C spectrum;

FIG. 21 is the product (2af)¹H spectrum; FIG. 22 is of the product (2af)¹³And (4) C spectrum.

Detailed Description

In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are some, but not all, embodiments of the present invention.

Thus, the following detailed description of the embodiments of the present invention, presented in the figures, is not intended to limit the scope of the invention, as claimed, but is merely representative of selected embodiments of the invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

The catalyst is formed by coordination of the chiral amide ligand and the iridium metal, and the catalyst can realize that the imine compound generates the corresponding amine compound under mild and environment-friendly conditions. The principle of its reaction can be described as:

first, the catalyst exchanges with chlorine in the presence of formic acid to give compound a, then by liberation of CO2 an active intermediate B is formed which forms with the unsaturated double-bonded imine a four-membered ring compound C, then by a series of protonations to give the amine compound.

The technical scheme is as follows:

a method of synthesizing an amine by catalytic reduction of an imine, the method comprising the steps of:

step 1: placing a sulfimide compound and a catalyst I in a reaction bottle according to a mass molar ratio of 1:0.01 at normal temperature and normal pressure, adding a formic acid and triethylamine solution according to a volume ratio of 5:2, and reacting in a water solvent for 1-15 min to obtain a reaction product; the reaction expression is as follows:

r1 represents aromatic ring with different substituent groups, R2 is halogen, methyl and other groups

Step 2: after the reaction in the step 1 is finished, water and ethyl acetate are sequentially and slowly added into the obtained reaction product, the mixture is fully stirred and then is kept stand for layering, the separated water layer is extracted by ethyl acetate, the ethyl acetate extract and the separated organic layer are combined, then the mixture is respectively washed by saturated saline solution and dried by anhydrous sodium sulfate, a crude product is obtained after the ethyl acetate solvent is removed by evaporation, and then the amine compound is obtained by silica gel column chromatography separation and purification.

In the step 1, the catalyst I is formed by coordination of chiral amide ligand and metallic iridium.

The present invention will be further described with reference to specific embodiments.

The following examples, all reactions were carried out without nitrogen protection, and the reactions were carried out at room temperature in air with water as solvent. All chemicals were commercially available without further purification unless otherwise indicated.

Thin Layer Chromatography (TLC) used 60F254 silica gel plates, 254 and 365nm uv light.

Silica gel with the particle size of 300-400 meshes is used for silica gel column chromatography. NMR (400 MHz)¹HNMR，100MHz¹³C NMR) was chloroform or acetone with Tetramethylsilane (TMS) as an internal standard.

Chemical shifts are in ppm and coupling constants are in Hz. In 1H NMR, δ represents chemical shift, s represents singlet, d represents doublet, t represents triplet, q represents quartet, and m represents multiplet. In that¹³In C NMR, δ represents a chemical shift.

High Resolution Mass Spectrometry (HRMS) uses ESI ionization.

The process of forming the catalyst by coordinating the chiral amide ligand and the metallic iridium is shown as the following reaction equation:

(1) at room temperature, (2S, 3aS, 7aS) -octahydro-1H-indole-2-carboxylic acid (1-1) and di-tert-butyl diacid (Boc) are added in sequence according to the reaction molar ratio of 1:1.1:1.1₂O) and triethylamine were stirred in dichloromethane solution overnight until complete conversion. And then, adjusting the pH value of the reaction mixture to 7-8 by using a citric acid solution. The organic layer was separated and the inorganic layer was extracted 3-5 times with 50ml each time of dichloromethane. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and concentrated to give compound 2-1, which was used directly in the next step;

(2) dropwise adding ethyl chloroformate (1.2 equivalents) into a dichloromethane solution of a compound 2-1 and triethylamine in a reaction molar ratio of 1:1.1, stirring at 0 ℃ for 1 hour, then continuously adding amine (1.2 equivalents), stirring the reaction mixture overnight, adjusting the pH with a citric acid solution and saturated sodium carbonate to be 7-9, and then washing with brine; the organic layer was dried over anhydrous sodium sulfate and concentrated to give compound 3-1;

(3) trifluoroacetic acid (20.0 equivalents) was added to a dichloromethane solution of 3 to 11.0 equivalents of the compound, the solution was stirred until complete conversion, and then saturated Na was added₂CO₃The reaction was neutralized to pH 9 and the aqueous layer was extracted with dichloromethane (3 × 50.0mL), the combined organic layers were washed with brine, and Na₂SO₄Drying and concentrating to obtain amides A-C which are respectively a compound A, a compound B and a compound C.

(2S, 3aS, 7aS) -N- (p-tolyl) octahydro-1H-indole-2-carboxamide (A):

as shown in fig. 1 and 2. Compound a is a white solid, melting point: 129.0-130.0 ℃.¹H NMR(400MHz,Chloroform-d)δ9.90(s,1H),7.48(d,J＝8.4Hz,2H),7.13(d,J＝8.2Hz,2H),3.84(dd,J＝10.7,4.7Hz,1H),3.36(q,J＝4.7Hz,1H),2.39-2.32(m,1H),2.31(s,3H),2.22-2.08(m,1H),2.04-1.94(m,1H),1.93-1.85(m,1H),1.65-1.54(m,3H),1.53-1.46(m,2H),1.43-1.35(m,1H),1.34-1.28(m,1H),1.27-1.17(m,1H)；¹³C NMR(101MHz,Chloroform-d)δ174.2,135.5,133.5,129.6,119.2,59.4,57.6,38.1,35.7,29.5,27.7,23.8,22.0,21.0；(+)-HRMS(ESI)m/z259.1807[M+H]⁺(cacld for C₁₆H₂₃N₂O,259.1810)。

(2S, 3aS, 7aS) -N- (4-methoxyphenyl) octahydro-1H-indole-2-carboxamide (B):

as shown in fig. 3 and 4, compound B is a white substance, melting point: 129.0-130.0 ℃.¹H NMR(400MHz,Chloroform-d)δ9.90(s,1H),7.48(d,J＝8.4Hz,2H),7.13(d,J＝8.2Hz,2H),3.84(dd,J＝10.7,4.7Hz,1H),3.36(q,J＝4.7Hz,1H),2.39-2.32(m,1H),2.31(s,3H),2.22-2.08(m,1H),2.04-1.94(m,1H),1.93-1.85(m,1H),1.65-1.54(m,3H),1.53-1.46(m,2H),1.43-1.35(m,1H),1.34-1.28(m,1H),1.27-1.17(m,1H)；¹³C NMR(101MHz,Chloroform-d)δ174.2,135.5,133.5,129.6,119.2,59.4,57.6,38.1,35.7,29.5,27.7,23.8,22.0,21.0；(+)-HRMS(ESI)m/z259.1807[M+H]⁺(cacld for C₁₆H₂₃N₂O,259.1810)。

(2S, 3aS, 7aS) -N- (4- (trifluoromethyl) phenyl) octahydro-1H-indole-2-carboxamide (C):

as shown in fig. 5 and 6, compound C is a white solid with a melting point: 83.0-84.0 ℃.¹H NMR(400MHz,Chloroform-d)10.22(s,1H),7.74(d,J＝8.5Hz,2H),7.60(d,J＝8.5Hz,2H),3.90(dd,J＝10.7,4.8Hz,1H),3.41(q,J＝5.1Hz,1H),2.48-2.30(m,1H),2.18-1.84(m,3H),1.75-1.39(m,6H),1.37-1.19(m,2H)；¹³C NMR(101MHz,Chloroform-d)δ174.5,140.8,126.4(q,J＝3.8Hz,1C),125.7(m,1C),122.9,118.9,59.5,57.8,38.2,35.7,29.5,27.7,23.6,22.1；(+)-HRMS(ESI)m/z313.1525[M+H]⁺(cacld for C₁₆H₂₀F₃N₂O,313.1528)。

(4) Reacting [ IrCp Cl₂]₂1.0 equivalent is mixed with corresponding ligand A-C (2.0 equivalents), catalyst Cat-1-Cat-3 is synthesized at room temperature, after stirring overnight,the yellow solution was evaporated to give a yellow solid, which gave catalyst I, which was used directly for the reduction of the imine.

The chemical structural formula of the catalyst Cat-1 is as follows:

as shown in FIGS. 7 and 8, the catalyst Cat-1 was a yellow solid having a melting point of 181.0 to 182.0 ℃.¹H NMR(400MHz,D₂O)δ7.32(d,J＝7.9Hz,2H),6.96(d,J＝7.9Hz,2H),3.86-3.72(m,2H),2.54-2.41(m,1H),2.39(s,3H),2.19-2.06(m,1H),1.99-1.85(m,1H),1.84-1.62(m,4H),1.61-1.53(m,2H),1.52-1.44(m,1H),1.43(s,15H),1.32-1.17(m,2H)；¹³C NMR(101MHz,D₂O)δ192.4,145.3,137.0,129.7,125.3,90.5,63.5,61.2,38.8,30.0,29.4,24.3,20.0,18.7,8.6；HRMS(ESI)forC₂₆H₃₇N₂OClIr(M⁺) CaCld for 621.22237, not found.

The chemical structural formula of the catalyst Cat-2 is as follows:

as shown in FIGS. 9 and 10, catalyst Cat-1 was a yellow solid with a melting point of 180.0-181.0 ℃.¹H NMR(400MHz,D₂O)δ7.08(d,J＝9.1Hz,2H),7.02(d,J＝9.1Hz,2H),3.85(s,3H),3.77-3.66(m,1H),2.55-2.38(m,1H),2.17-2.06(m,1H),1.96-1.87(m,1H),1.85-1.64(m,4H),1.61-1.51(m,2H),1.50-1.44(m,1H),1.42(s,15H),1.31-1.19(m,2H)；¹³C NMR(101MHz,D₂O)δ191.4,157.3,141.6,126.6,114.5,90.1,63.3,61.4,55.5,38.7,29.5,29.4,24.4,24.3,18.8,8.6；HRMS(ESI)for C₂₆H₃₇N₂O₂ClIr[M+H]⁺,Cacld for 637.21728,found 637.21484。

The chemical structural formula of the catalyst Cat-3 is as follows:

as shown in FIGS. 9 and 10, the catalyst Cat-3 was a yellow solid having a melting point of 191.0-192.0℃.¹H NMR(400MHz,D₂O)δ7.85(d,J＝8.3Hz,2H),7.26(d,J＝8.1Hz,2H),3.92(dd,J＝7.6,10.0Hz,1H),3.78-3.70(m,1H),2.55-2.42(m,1H),2.23-2.08(m,1H),2.01-1.89(m,2H),1.87-1.64(m,4H),1.54-1.44(m,1H),1.42(s,15H),1.33-1.23(m,2H)；¹³C NMR(101MHz,D₂O)δ190.6,151.4,126.7,126.6,126.4,89.9,63.3,61.4,38.8,29.3,24.4,24.3,23.0,18.8,8.51；HRMS(ESI)for C₂₆H₃₄N₂OClF₃Ir[M+H]⁺,Cacld for 675.19410,found 675.19177。

Example 1

The compound N-benzylbenzenesulfonylimide (1a) (0.5mmol), catalyst Cat-3(1 mol%), and water (2.0mL) were added to a reaction tube, and HCOOH: Et was added₃N (5:2) (1mL), reacting for 2-10min until the raw materials react completely. After the reaction is finished, water and ethyl acetate are slowly added into the obtained reaction product in sequence, the mixture is fully stirred and then stands for layering, the separated water layer is extracted by ethyl acetate, the ethyl acetate extract and the separated organic layer are combined, then the mixture is washed by saturated saline solution and dried by anhydrous sodium sulfate, the ethyl acetate solvent is removed by evaporation to obtain a crude product, and then the crude product is separated and purified by silica gel column chromatography to obtain the amine compound. After removal of the solvent, the crude residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate) to give the corresponding product N-benzylbenzenesulfonamide (2aa) (refer to the corresponding product).

As shown in fig. 11 and 12, N-benzylbenzenesulfonamide (2aa) was a colorless oil; the yield is 250.8mg, and the yield is 98%;¹H NMR(400MHz,Chloroform-d)δ7.89-7.82(m,2H),7.60-7.54(m,1H),7.52-7.44(m,2H),7.31-7.22(m,3H),7.21-7.14(m,2H),5.46(t,J＝6.3Hz,1H),4.13(d,J＝6.3Hz,2H)；¹³C NMR(100MHz,Chloroform-d)δ139.9,136.3,132.6,129.1,128.6,127.9,127.8,127.1,47.1。

example 2

The compound N- (4-methylbenzyl) benzenesulfonylimine (0.5mmol), catalyst I (1 mol%), and water (2.0mL) were added to a reaction tube, and HCOOH: Et3N (5:2) (1mL) was added and reacted for 2-10min until the starting material was reacted completely. After the reaction is finished, water and ethyl acetate are slowly added into the obtained reaction product in sequence, the mixture is fully stirred and then stands for layering, the separated water layer is extracted by ethyl acetate, the ethyl acetate extract and the separated organic layer are combined, then the mixture is washed by saturated saline solution and dried by anhydrous sodium sulfate, the ethyl acetate solvent is removed by evaporation to obtain a crude product, and then the crude product is separated and purified by silica gel column chromatography to obtain the amine compound. After removal of the solvent, the crude residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate) to give the corresponding product, N- (4-methylbenzyl) benzenesulfonamide (2 ab).

As shown in fig. 13 and 14, N- (4-methylbenzyl) benzenesulfonamide (2ab) is a white solid; the yield was 239.4mg, 98%;¹H NMR(400MHz,Chloroform-d)δ7.86(d,J＝7.8Hz,2H),7.56(d,J＝7.5Hz,1H),7.48(t,J＝7.7Hz,2H),7.06(m,4H),5.22(t,J＝6.0Hz,1H),4.07(d,J＝6.2Hz,2H),2.29(s,3H)；¹³C NMR(100MHz,Chloroform-d)δ139.9,137.6,133.3,132.6,129.3,129.1,127.9,127.1,47.0,21.1。

example 3

The compound N- (2-methoxybenzyl) benzenesulfonylimine (1c) (0.5mmol), catalyst I (1 mol%), water (2.0mL) were added to the reaction tube, HCOOH: Et3N (5:2) (1mL) was added and the reaction was carried out for 2-10min until the starting material was completely reacted. After the reaction is finished, water and ethyl acetate are slowly added into the obtained reaction product in sequence, the mixture is fully stirred and then stands for layering, the separated water layer is extracted by ethyl acetate, the ethyl acetate extract and the separated organic layer are combined, then the mixture is washed by saturated saline solution and dried by anhydrous sodium sulfate, the ethyl acetate solvent is removed by evaporation to obtain a crude product, and then the crude product is separated and purified by silica gel column chromatography to obtain the amine compound. After removal of the solvent, the crude residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate) to give the corresponding product N- (2-methoxybenzyl) benzenesulfonamide (2 ac).

N- (2-methoxybenzyl) benzenesulfonylimide (2ac) as a white solid, as shown in FIGS. 15-16, at a yield of 280.4mg and 97%;¹H NMR(400MHz,Chloroform-d)δ7.91-7.71(m,2H),7.52-7.46(m,1H),7.44-7.36(m,2H),7.23-7.15(m,1H),7.09-7.05(m,1H),6.80(t,J＝7.4Hz,1H),6.72(d,J＝8.2Hz,1H),5.41(t,J＝6.2Hz,1H),4.18(d,J＝6.4Hz,2H),3.72(s,3H)；¹³C NMR(100MHz,Chloroform-d)δ157.2,140.3,132.3,129.8,129.4,128.8,127.0,124.2,120.5,110.1,55.2,44.0。

example 4

The compound N- (4-methoxybenzyl) benzenesulfonylimine (1d) (0.5mmol), catalyst I (1 mol%), water (2.0mL) were added to the reaction tube, and HCOOH: Et was added₃N (5:2) (1mL), reacting for 2-10min until the raw materials react completely. After the reaction is finished, water and ethyl acetate are slowly added into the obtained reaction product in sequence, the mixture is fully stirred and then stands for layering, the separated water layer is extracted by ethyl acetate, the ethyl acetate extract and the separated organic layer are combined, then the mixture is washed by saturated saline solution and dried by anhydrous sodium sulfate, the ethyl acetate solvent is removed by evaporation to obtain a crude product, and then the crude product is separated and purified by silica gel column chromatography to obtain the amine compound. After removal of the solvent, the crude residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate) to give the corresponding product, N- (4-methoxybenzyl) benzenesulfonamide (2 ad).

N- (4-methoxybenzyl) benzenesulfonamide (2ad) as a colorless oil; as shown in FIGS. 17 and 18, the yield was 260.9mg, 98%;¹H NMR(400MHz,Chloroform-d)δ7.87-7.80(m,2H),7.56(t,J＝7.4Hz,1H),7.47(t,J＝7.6Hz,2H),7.07(d,J＝8.6Hz,2H),6.75(d,J＝8.6Hz,2H),5.17(t,J＝5.9Hz,1H),4.04(d,J＝6.1Hz,2H),3.74(s,3H)；¹³C NMR(100MHz,Chloroform-d)δ159.2,140.0,132.7,129.3,129.2,128.3,127.1,114.0,55.3,46.8。

example 5

The compound N- (4-chlorobenzyl) benzenesulfonylimine (1e) (0.5mmol), catalyst I (1 mol%), water (2.0mL) were added to the reaction tube, and HCOOH: Et was added₃N (5:2) (1mL), reacting for 2-10min until the raw materials react completely. And (2) sequentially and slowly adding water and ethyl acetate into the obtained reaction product, fully stirring, standing for layering, extracting the separated water layer with ethyl acetate, combining the ethyl acetate extract and the separated organic layer, washing with saturated saline solution, drying with anhydrous sodium sulfate, evaporating to remove the ethyl acetate solvent to obtain a crude product, and then separating and purifying by silica gel column chromatography to obtain the amine compound. After removal of the solvent, the crude residue is purified by column chromatography on silica gel (petroleum ether/ethyl acetate) to give the corresponding product N- (4-chlorobenzyl) benzene sulfonic acidAmide (2 ae).

The N- (4-chlorobenzyl) benzenesulfonamide (2ae) is a white solid, the yield is 230.6mg, and the yield is 98%; as shown in figures 19 and 20 of the drawings,¹H NMR(400MHz,Chloroform-d)δ7.84(d,J＝7.7Hz,2H),7.59(t,J＝7.4Hz,1H),7.49(t,J＝7.7Hz,2H),7.21(d,J＝8.4Hz,2H),7.12(d,J＝8.4Hz,2H),5.44(t,J＝6.2Hz,1H),4.10(d,J＝6.3Hz,2H)；¹³C NMR(100MHz,Chloroform-d)δ139.8,135.0,133.7,132.9,129.3,129.2,128.8,127.1,46.5。

example 6

The compound N- (2-chlorobenzyl) benzenesulfonylimine (1f) (0.5mmol), catalyst I (1 mol%), water (2.0mL) were added to the reaction tube, and HCOOH: Et was added₃N (5:2) (1mL), reacting for 2-10min until the raw materials react completely. And (2) sequentially and slowly adding water and ethyl acetate into the obtained reaction product, fully stirring, standing for layering, extracting the separated water layer with ethyl acetate, combining the ethyl acetate extract and the separated organic layer, washing with saturated saline solution, drying with anhydrous sodium sulfate, evaporating to remove the ethyl acetate solvent to obtain a crude product, and then separating and purifying by silica gel column chromatography to obtain the amine compound. After removal of the solvent, the crude residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate) to give the corresponding product N- (2-chlorobenzyl) benzenesulfonamide (2 af).

The product, N- (2-chlorobenzyl) benzenesulfonamide (2af), was a colorless oil, as shown in FIGS. 21 and 22, in a yield of 270.2mg, 97%,¹H NMR(400MHz,Chloroform-d)δ7.83(d,J＝8.1Hz,2H),7.52(t,J＝7.3Hz,1H),7.43(t,J＝7.7Hz,2H),7.33-7.26(m,1H),7.25-7.20(m,1H),7.19-7.08(m,2H),5.60(t,J＝6.2Hz,1H),4.25(d,J＝6.5Hz,2H)；¹³C NMR(100MHz,Chloroform-d)δ139.9,133.8,133.2,132.6,130.1,129.4,129.2,129.0,127.0,126.9,45.0。

the above description is only for the purpose of illustrating the technical solutions of the present invention and not for the purpose of limiting the same, and other modifications or equivalent substitutions made by those skilled in the art to the technical solutions of the present invention should be covered within the scope of the claims of the present invention without departing from the spirit and scope of the technical solutions of the present invention.