A method for synthesizing tertiary amines and secondary amines by highly selective aldehyde reductive amination under catalyst-free conditions

Abstract

The present invention provides a method for synthesizing tertiary and secondary amines through highly selective aldehyde reductive amination under catalyst-free conditions, belonging to the field of organic synthesis. The method uses primary amines and aldehydes as raw materials and synthesizes tertiary and secondary amines through chemoselective reductive amination using different borane complexes. The main advantages of this method include the absence of a catalyst, high yield, mild reaction conditions, and a one-pot reaction with short reaction time. Therefore, the method provided by the present invention provides an effective solution for the future synthesis of other high-value tertiary and secondary amine structures.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic chemistry, including the synthesis of fine chemicals and pharmaceutical intermediates, and particularly relates to a method for synthesizing tertiary amines and secondary amines through highly selective aldehyde reductive amination under catalyst-free conditions. Technical Background

[0002] The skeletons of tertiary and secondary amines are widely used in pharmaceutical intermediates, natural products, and material molecules. The structures of cyclic aliphatic amines appear frequently in the new drugs currently under development. [Afanasyev OI, Kuchuk E, Usanov DL, et al. Reductive Amination in the Synthesis of Pharmaceuticals [J]. Chem Rev, 2019, 119(23): 11857-911.] The current methods for synthesizing tertiary and secondary amines are mainly through reductive amination, direct C-H bond formation of C-N bonds, and halide C-N cross-coupling. These methods require expensive catalysts and require the design of various ligands to improve catalytic activity. Reductive amination by high-pressure hydrogenation requires a specific reactor, and the reaction energy consumption is high, requiring a specific hydrogenation catalyst. Therefore, it is of great significance to find a green and atom-efficient reductive amination method. [He J,Chen L,Liu S,et al.Sustainable access to renewable N-containingchemicals from reductive amination of biomass-derived platform compounds[J].Green Chem,2020,22(20):6714-47. S,Plessow P,Schelwies M,et al.AlcoholAmination with Aminoacidato Cp*Ir(III)-Complexes as Catalysts:Dissociation of the Chelating Ligand during Initiation[J].ACS Catal,2014,4(1):152-61.Li C,WanK-f,Guo Fy,et al.Iridium-Catalyzed Alkylation of Amine and Nitrobenzene withAlcohol to Tertiary Amine under Base-and Solvent-Free Conditions[J].J OrgChem,2019,84(4):2158-68.] Summary of the Invention

[0003] The present invention provides a highly selective method for synthesizing tertiary and secondary amines through the reductive amination of aldehydes under catalyst-free conditions. This method utilizes different borane complexes for hydrogen transfer reductive amination of primary amines and aldehydes in a one-pot process. This method is catalyst-free, has high yields, and good selectivity. The hydrogen transfer reagent is readily available and inexpensive, and the substrates are widely applicable.

[0004] The specific steps are:

[0005] Under inert gas, add the primary amine substrate to a 25 mL Schlenk tube, cool to 0°C in an ice bath, add the borane complex, stir for 5 minutes, and then slowly add the aldehyde dropwise. Finally, seal the Schlenk tube and heat to react. TLC is used to monitor the reaction and determine the specific reaction time. The synthetic route is as follows:

[0006]

[0007] After the reaction is completed, the organic solvent is dried by spin drying and the product is purified by column chromatography, with the eluent being a mixed solution of petroleum ether and ethyl acetate.

[0008] Wherein: the reaction temperature is 0-100°C, and the reaction time is 0.5h to 48h.

[0009] Where: R 1 and R 2 is selected from alkyl, substituted alkyl, aryl, substituted aryl, R 1 and R 2 Same or different.

[0010] The borane complex is one of borane tetrahydrofuran complex, triethylamine borane complex, dimethylamine borane complex, tert-butylamine borane complex, ammonia borane and 1,3,2-oxazoline borane complex, and the amount of the borane complex is 0.5 to 2 equivalents.

[0011] Wherein: the amount of aldehyde used is 1 to 8 equivalents.

[0012] The reaction additive is one of triethylamine, tetramethylethylenediamine, hexamethylphosphonic triamide and cesium carbonate, and the amount of the additive is 0 to 2 equivalents.

[0013] Treatment and purification methods: First, the solvent after the reaction is dried by spin drying, and then purified and separated by column chromatography; for column chromatography, 200-300 mesh silica gel or alkaline alumina can be selected as the stationary phase, and the eluent is generally a mixed system of petroleum ether and ethyl acetate.

[0014] The invention has the following advantages:

[0015] 1. High yield, mild reaction conditions, and cheap and readily available hydrogen transfer reagents;

[0016] 2. No catalyst is required, and highly selective synthesis of tertiary and secondary amines can be achieved simply by using different boranes;

[0017] 3. The reaction is efficient, and primary amines can be synthesized into tertiary amine products in one step. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 The hydrogen and carbon nuclear magnetic resonance spectra of N,N-dibutylaniline prepared in Example 1;

[0019] Figure 2 The H NMR spectrum and C NMR spectrum of N,N-dibutyl-4-nitroaniline prepared in Example 2;

[0020] Figure 3 The H NMR and C NMR spectra of methyl 4-(dibutylamino)benzoate prepared in Example 3;

[0021] Figure 4 The H NMR spectrum and C NMR spectrum of N,N-dibutyl-[1,1'-biphenyl]-3-amine prepared in Example 4;

[0022] Figure 5 The H NMR spectrum and C NMR spectrum of N,N-dibutylnaphthalene-1-amine prepared in Example 5;

[0023] Figure 6 The hydrogen and carbon nuclear magnetic resonance spectra of N,N-dipropylaniline prepared in Example 6;

[0024] Figure 7 The H NMR spectrum and C NMR spectrum of N,N-dibutylphenethylamine prepared in Example 7;

[0025] Figure 8 The H NMR spectrum and C NMR spectrum of tribenzylamine prepared in Example 8;

[0026] Figure 9 The H NMR spectrum and C NMR spectrum of N-butylaniline prepared in Example 9;

[0027] Figure 10 The H NMR spectrum and C NMR spectrum of N-butyl-3-nitroaniline prepared in Example 10; Figure 11 H NMR and C NMR of N-butyl-[1,1'-biphenyl]-2-amine prepared in Example 11;

[0028] Figure 12 The H NMR spectrum and C NMR spectrum of the dibenzylamine prepared in Example 12; DETAILED DESCRIPTION

[0029] The following further illustrates and describes the technical solution of the present invention in conjunction with specific embodiments, but does not limit the present invention. Simple replacements or improvements made by those skilled in the art to the present invention are all within the technical solution protected by the present invention.

[0030] Example 1: Synthesis of N,N-dibutylaniline

[0031] Under argon, 1 mmol of aniline (1 equiv.) was added to a 25 mL Schlenk tube. After cooling to 0°C in an ice bath, borane tetrahydrofuran complex (1 M, 2 mL, 2 equiv.) was added, followed by the slow dropwise addition of 6 mmol of n-butyraldehyde (6 equiv., 432.6 mg). After the addition was complete, the Schlenk tube was sealed and the temperature was raised to 70°C and refluxed for 24 hours. After the reaction, the solvent was removed by rotary evaporation under reduced pressure, and the residue was purified by column chromatography with an eluent ratio of 100:1, yielding 87%.

[0032]

[0033] The H NMR and C NMR spectra of the product N,N-dibutylaniline are as follows: Figure 1 Shown: 1H NMR(400MHz,Chloroform-d)δ7.25–7.17(m,2H),6.69–6.60(m,3H),3.30–3.24(m ,4H),1.58(ddt,J=9.2,7.7,3.4Hz,4H),1.41–1.32(m,4H),0.97(t,J=7.3Hz,6H). 13 C NMR (101MHz, Chloroform-d) δ148.30,129.31,115.16,111.78,50.90,29.53,20.51,14.18.

[0034] Example 2: Synthesis of N,N-dibutyl-4-nitroaniline

[0035] Under argon, 1 mmol of 4-nitroaniline (1 equiv.) was added to a 25 mL Schlenk tube. After cooling to 0°C in an ice bath, borane tetrahydrofuran complex (1 M, 2 mL, 2 equiv.) was added, followed by the slow dropwise addition of 6 mmol of n-butyraldehyde (6 equiv., 432.6 mg). After the addition was complete, the Schlenk tube was sealed and the temperature was raised to 70°C, followed by reflux for 24 hours. After the reaction, the solvent was removed by rotary evaporation under reduced pressure, and the residue was purified by column chromatography using a 30:1 ratio of eluent to yield 67%.

[0036]

[0037] The H NMR and C NMR spectra of the product N,N-dibutyl-4-nitroaniline are as follows: Figure 2 As shown: 1 H NMR(600MHz,Chloroform-d)δ8.11–8.06(m,2H),6.57–6.52(m,2H),3.36(t,J=7.9Hz,4H),1.60(q,J=7.8Hz,4H),1.43–1.33(m,4H),0.98(t,J=7.4Hz,6H). 13 C NMR (151 MHz, CDCl 3) δ152.74,136.32,126.54,110.08,51.20,29.33,20.35,14.02.

[0038] Example 3: Synthesis of methyl 4-(dibutylamino)benzoate

[0039] Under argon, 1 mmol (1 equiv.) of methyl 4-aminobenzoate was added to a 25 mL Schlenk tube. After cooling to 0°C in an ice bath, borane tetrahydrofuran (1 M, 2 mL, 2 equiv.) was added, followed by the slow dropwise addition of 6 mmol (432.6 mg) of n-butyraldehyde. After the addition was complete, the Schlenk tube was sealed and the temperature was raised to 70°C, followed by reflux for 24 hours. After the reaction, the solvent was removed by rotary evaporation under reduced pressure, and the residue was purified by column chromatography using a 100:1 ratio of eluent to yield 53%.

[0040]

[0041] The H NMR and C NMR spectra of the product 4-(dibutylamino)benzoic acid methyl ester are as follows: Figure 3 As shown: 1 HNMR(600MHz,Chloroform-d)δ7.88–7.84(m,2H),6.59–6.55(m,2H),3.84(s,3H),3.3 1(t,J=7.8Hz,4H), 1.58(p,J=7.7Hz,4H), 1.36(q,J=7.3Hz,4H), 0.96(t,J=7.4Hz,6H). 13 CNMR (151MHz, CDCl3) δ167.62,151.51,131.56,116.03,110.36,51.51,50.83,29.40,20.39,14.07.

[0042] Example 4: Synthesis of N,N-dibutyl-[1,1'-biphenyl]-3-amine

[0043] Under argon, 1 mmol of 3-aminobiphenyl (1 equiv.) was added to a 25 mL Schlenk tube. After cooling to 0°C in an ice bath, borane tetrahydrofuran complex (1 M, 2 mL, 2 equiv.) was added, followed by the slow dropwise addition of 6 mmol of n-butyraldehyde (6 equiv., 432.6 mg). After the addition was complete, the Schlenk tube was sealed and the temperature was raised to 70°C, followed by reflux for 24 hours. After the reaction, the solvent was removed by rotary evaporation under reduced pressure, and the residue was purified by column chromatography with an eluent ratio of 50:1, yielding 64%.

[0044]

[0045] The H NMR and C NMR spectra of the product N, N-dibutyl-[1,1'-biphenyl]-3-amine are as follows: Figure 4 As shown: 1HNMR(600MHz,Chloroform-d)δ7.59(d,J=7.5Hz,2H),7.46–7.41(m,2H),7.37–7.31(m,1H),7.31–7.25(m,1H),6.88–6. 83(m,2H),6.68–6.64(m,1H),3.33(t,J=7.3Hz,4H),1.63(q,J=7.8Hz,4H),1.39(q,J=7.2Hz,4H),0.98(t,J=7.2Hz,6H). 13 C NMR (151MHz, CDCl3) δ148.65,142.68,142.51,129.65,128.70,127.43,127.0 9,114.56,110.90,110.81,77.37,77.16,76.95,51.01,29.62,20.54,14.18.

[0046] Example 5: N,N-dibutylnaphthalene-1-amine

[0047] Under argon, 1 mmol of 1-naphthylamine (1 equiv.) was added to a 25 mL Schlenk tube. After cooling to 0°C in an ice bath, borane tetrahydrofuran complex (1 M, 2 mL, 2 equiv.) was added, followed by the slow dropwise addition of 6 mmol of n-butyraldehyde (6 equiv., 432.6 mg). After the addition was complete, the Schlenk tube was sealed and the temperature was raised to 70°C, followed by reflux for 24 hours. After the reaction, the solvent was removed by rotary evaporation under reduced pressure, and the residue was purified by column chromatography using a 60:1 ratio of eluent to yield 71%.

[0048]

[0049] The H NMR and C NMR spectra of the product N, N-dibutyl-[1,1'-biphenyl]-3-amine are as follows: Figure 5 As shown: 1 HNMR(600MHz,Chloroform-d)δ8.38–8.28(m,1H),7.85–7.79(m,1H),7.61–7.52(m,1H),7.49–7.42(m,2H),7.42–7 .36(m,1H),7.20–7.13(m,1H),3.13(t,J=7.3Hz,4H),1.53–1.44(m,4H),1.32–1.27(m,4H),0.86(t,J=7.6Hz,6H). 13C NMR (151MHz, CDCl3) δ148.83,135.03,131.27,128.25,125.74,125.65,125.1 5,124.41,123.25,118.04,77.37,77.16,76.95,54.18,29.43,20.67,14.15.

[0050] Example 6: N,N-dipropylaniline

[0051] Under argon, 1 mmol of aniline (1 equiv.) was added to a 25 mL Schlenk tube. After cooling to 0°C in an ice bath, borane tetrahydrofuran complex (1 M, 2 mL, 2 equiv.) was added, followed by the slow dropwise addition of 6 mmol of n-propionaldehyde (6 equiv., 404.5 mg). After the addition was complete, the Schlenk tube was sealed and the temperature was raised to 70°C and refluxed for 24 hours. After the reaction, the solvent was removed by rotary evaporation under reduced pressure, and the residue was purified by column chromatography with an eluent ratio of 100:1, yielding 83%.

[0052]

[0053] The H NMR and C NMR spectra of the product N,N-dipropylaniline are as follows: Figure 6 As shown: 1 H NMR (600MHz, Chloroform-d) δ7.28(d,J=7.9Hz,2H),6.71(t,J=7.8Hz,3H),3.30(t,J=7.7Hz,4H),1.68(h,J=7.6Hz,4H),1.00(t,J=7.6Hz,6H). 13 C NMR (151MHz, Chloroform-d) δ148.25,129.29,115.15,111.70,52.96,20.48,11.58.

[0054] Example 7: N,N-dibutylphenethylamine

[0055] Under argon, 1 mmol of phenylethylamine (1 equiv.) was added to a 25 mL Schlenk tube. After cooling to 0°C in an ice bath, borane tetrahydrofuran complex (1 M, 2 mL, 2 equiv.) was added, followed by the slow dropwise addition of 6 mmol of n-butyraldehyde (6 equiv., 432.6 mg). Following the completion of the addition, 1 mmol of hexamethylphosphonic triamide (179.2 mg, 1 equiv.) was added. The Schlenk tube was sealed and the temperature was raised to 70°C and refluxed for 24 hours. After completion of the reaction, the solvent was removed by rotary evaporation under reduced pressure, and the residue was purified by column chromatography using a 20:1 ratio of eluent to yield 81%.

[0056]

[0057] The H NMR and C NMR spectra of the product N,N-dibutylphenylethylamine are as follows: Figure 7 As shown: 1 HNMR(600MHz,Chloroform-d)δ7.32–7.27(m,2H),7.24–7.17(m,3H),2.80–2.67(m,4H),2 .51(t,J=7.8Hz,4H),1.47(p,J=7.7Hz,4H),1.33(h,J=7.3Hz,4H),0.94(t,J=7.5Hz,6H). 13 CNMR(151MHz,Chloroform-d)δ141.00,128.83,128.41,125.94,56.21,53.88,33.50,29.36,20.89,14.25.

[0058] Example 8: Tribenzylamine

[0059] Under argon, 1 mmol of benzylamine (1 equiv.) was added to a 25 mL Schlenk tube. After cooling to 0°C in an ice bath, triethylamine borane complex (228 mg, 2 equiv.) was added, followed by the slow dropwise addition of 6 mmol of benzaldehyde (6 equiv., 636.7 mg). After the addition was complete, the Schlenk tube was sealed and the temperature was raised to 70°C, followed by reflux for 24 hours. After the reaction, the solvent was removed by rotary evaporation under reduced pressure, and the residue was purified by column chromatography using an eluent ratio of 100:1 with a yield of 84%.

[0060]

[0061] The H NMR and C NMR spectra of the product tribenzylamine are as follows Figure 8 As shown: 1 H NMR (600MHz, Chloroform-d) δ7.44–7.40(m,6H),7.36–7.30(m,6H),7.26–7.22(m,3H),3.57(s,6H). 13 CNMR (151MHz, CDCl3) δ139.79,128.88,128.35,126.99,58.06.

[0062] Example 9: N-Butylaniline

[0063] To a 10 mL Schlenk tube equipped with a stirrer, add aniline (1.0 mmol, 1 equiv.) and dimethylamine borane complex (2 mmol, 117.8 mg, 2 equiv.) under argon. The mixture was then cooled to 0°C in an ice bath and stirred thoroughly. Then, butyraldehyde (6 mmol, 432.6 mg, 6 equiv.) was slowly added dropwise. The addition rate was carefully controlled. A vigorous exotherm and the evolution of colorless gas occurred during the addition. When the reaction became very intense, stop the addition of butyraldehyde and allow it to subside. Continue the addition of butyraldehyde after the reaction subsided. After the addition was complete, raise the temperature to 70°C and seal the tube for 24 h. After the reaction, remove the solvent by rotary evaporation under reduced pressure. The residue was purified by column chromatography using a 50:1 ratio of eluent to yield 81%.

[0064]

[0065] The H NMR and C NMR spectra of the product N-butylaniline are as follows: Figure 9 As shown: 1 H NMR(400MHz,Chloroform-d)δ7.24–7.13(m,2H),6.76–6.67(m,1H),6.66–6.58(m,2H ),3.12(t,J=7.2Hz,2H),1.69–1.58(m,2H),1.51–1.38(m,2H),0.97(t,J=7.3Hz,3H). 13 C NMR (151MHz, Chloroform-d) δ148.60,129.27,117.09,112.72,43.70,31.71,20.38,14.01.

[0066] Example 10: N-butyl-3-nitroaniline

[0067] To a 10 mL Schlenk tube equipped with a stirrer, add 3-nitroaniline (1.0 mmol, 1 equiv.) and dimethylamine borane complex (2 mmol, 117.8 mg, 2 equiv.) under argon. The mixture was then cooled to 0°C in an ice bath and stirred thoroughly. Then, butyraldehyde (6 mmol, 432.6 mg, 6 equiv.) was slowly added dropwise. The addition rate was carefully controlled. A vigorous exotherm and the evolution of colorless gas occurred during the addition. If the reaction became very intense, stop the addition of butyraldehyde and allow it to subside. Continue the addition of butyraldehyde after the reaction subsided. After the addition was complete, the temperature was raised to 70°C and the tube was sealed for 24 h. After the reaction, the solvent was removed by rotary evaporation under reduced pressure. The residue was purified by column chromatography using a 10:1 ratio of eluent to yield 52%.

[0068]

[0069] The H NMR and C NMR spectra of the product N-butyl-3-nitroaniline are as follows: Figure 10 As shown: 1 HNMR(400MHz,Chloroform-d)δ7.54–7.46(m,1H),7.41–7.35(m,1H),7.29–7.23(m,1H),6.88–6.82(m ,1H),3.97(s,1H),3.16(t,J=7.1Hz,2H),1.69–1.59(m,2H),1.52–1.40(m,2H),0.98(t,J=7.3Hz,3H). 13 C NMR (151MHz, Chloroform-d) δ149.57,149.32,129.74,118.73,111.67,106.15,43.58,31.40,20.33,13.96.

[0070] Example 11: N-butyl-[1,1'-biphenyl]-2-amine

[0071] To a 10 mL Schlenk tube equipped with a stirrer, add 2-aminobiphenyl (1.0 mmol, 1 equiv.) and dimethylamine borane complex (2 mmol, 117.8 mg, 2 equiv.) under argon. The mixture was then cooled to 0°C in an ice bath and stirred thoroughly. Then, butyraldehyde (6 mmol, 432.6 mg, 6 equiv.) was slowly added dropwise. The addition rate was carefully controlled. A vigorous exotherm and the evolution of colorless gas occurred during the addition. When the reaction became intense, stop the addition of butyraldehyde and allow it to subside. Continue the addition of butyraldehyde after the reaction subsided. After the addition was complete, raise the temperature to 70°C and seal the tube for 24 h. After the reaction, remove the solvent by rotary evaporation under reduced pressure. The residue was purified by column chromatography using a 30:1 ratio of eluent to yield 55%.

[0072]

[0073] The H NMR and C NMR spectra of the product N-butyl-[1,1'-biphenyl]-2-amine are as follows Figure 11 As shown: 1 HNMR(400MHz,Chloroform-d)δ7.49–7.41(m,4H),7.39–7.32(m,1H),7.28–7.22(m,1H),7.12–7.07(m,1H),6.80 –6.68(m,2H),3.90(brs,1H),3.11(t,J=7.1Hz,2H),1.58–1.50(m,2H),1.41–1.30(m,2H),0.92(t,J=7.3Hz,3H). 13C NMR (151MHz, Chloroform-d) δ145.43,139.72,130.31,129.47,128.99,128.83,127.57,127.26,116.69,110.42,43.80,31.56,20.43,14.00.

[0074] Example 12: Dibenzylamine

[0075] To a 10 mL Schlenk tube equipped with a stirrer, benzylamine (1.0 mmol, 1 equiv.) and dimethylamine borane complex (1 mmol, 58.9 mg, 1 equiv.) were added under argon. The mixture was then cooled to 0°C in an ice bath and stirred thoroughly. Then, benzaldehyde (3 mmol, 318.3 mg, 3 equiv.) was slowly added dropwise. The addition rate was carefully controlled. A vigorous exotherm and the evolution of colorless gas were observed during the addition. When the reaction became very intense, the addition of butyraldehyde was stopped. Continued addition of butyraldehyde occurred after the reaction subsided. After the addition was complete, the temperature was raised to 70°C and the tube was sealed for 24 h. After the reaction, the solvent was removed by rotary evaporation under reduced pressure. The residue was purified by column chromatography using a 5:1 ratio of eluent to yield 78%.

[0076]

[0077] The H NMR and C NMR spectra of the product dibenzylamine are as follows: Figure 11 As shown: 1 H NMR (600MHz, Chloroform-d) δ7.47–7.26 (m, 10H), 4.62 (d, J = 2.5Hz, 4H), 2.82–2.71 (m, 1H), 2.76 (brs, 1H). 13 C NMR (151MHz, Chloroform-d) δ140.90,128.55,127.60,127.05,65.08.

Claims

1. A method for synthesizing tertiary amines and secondary amines by highly selective aldehyde reductive amination under catalyst-free conditions, comprising the following steps: (1) Under inert gas protection, add the primary amine substrate to a 25 mL Schlenk tube, cool to 0°C in an ice bath, add the borane complex, stir for 5 minutes, and then slowly add the aldehyde dropwise. Finally, seal the Schlenk tube and heat to react. The reaction process is monitored by thin layer chromatography to determine the specific reaction time. The primary amine substrate is any one of aniline, 4-nitroaniline, methyl 4-aminobenzoate, 3-aminobiphenyl, 1-naphthylamine or phenylethylamine, a borane tetrahydrofuran complex is added as a borane complex, and the aldehyde is n-butyraldehyde or n-propionaldehyde to synthesize the corresponding tertiary amine; The primary amine substrate is any one of aniline, 3-nitroaniline or 2-aminobiphenyl, dimethylamine borane complex is added as the borane complex, and the aldehyde is butyraldehyde to synthesize the corresponding secondary amine; The primary amine substrate is benzylamine, triethylamine borane complex is added as borane complex, and the aldehyde is benzaldehyde to synthesize the corresponding tertiary amine; dimethylamine borane complex is added as borane complex, and the aldehyde is benzaldehyde to synthesize the corresponding secondary amine; (2) After the reaction is completed, the organic solvent in step (1) is dried by rotary evaporation and purified by column chromatography to obtain the product, wherein the eluent is a mixed solution of petroleum ether and ethyl acetate.

2. The method for synthesizing tertiary amines and secondary amines by highly selective aldehyde reductive amination under catalyst-free conditions according to claim 1, characterized in that: The reaction temperature is 0-100° C., and the reaction time is 0.5 h to 48 h.

3. The method for synthesizing tertiary amines and secondary amines by highly selective aldehyde reductive amination under catalyst-free conditions as claimed in claim 1, characterized in that: The amount of the aldehyde used is 1 to 8 equivalents.

4. The method for synthesizing tertiary amines and secondary amines by highly selective aldehyde reductive amination under catalyst-free conditions according to claim 1, wherein: In the step (2), the organic solvent after the reaction is first dried by spin drying and then purified and separated by column chromatography; the column chromatography selects 200-300 mesh silica gel or alkaline alumina as the stationary phase, and the eluent is a mixed system of petroleum ether and ethyl acetate.

Images