Synthesis method of alpha-aminonitrile compound

Abstract

The invention provides a synthesis method of an alpha-aminonitrile compound, and relates to the technical field of organic synthesis. The synthesis method provided by the invention comprises the following step: in an acidic solvent environment, under the action of a photocatalyst and a reducing agent, reacting a fatty amine compound I, a fatty aldehyde / ketone compound II and a cyano donor under illumination to generate the alpha-aminonitrile compound III. The raw materials are easy to obtain, the reaction conditions are mild, the compatibility of functional groups is good, the application range of substrates is wide, and the pollution to the environment is small.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a method for synthesizing alpha-amino nitrile compounds. Background Art

[0002] Introducing a carbon atom at the α-position of an amine compound can significantly change the physical, chemical and biological properties of the original amine compound. The compound obtained by introducing a cyano group (-CN) at the α-position of an amine compound can contain both an amino group and a cyano group on the same carbon atom. This type of compound is also called an α-aminonitrile compound. Since amino and cyano groups play an important role in synthetic chemistry and are prone to various functional group transformations, α-aminonitrile compounds have gradually become key precursors of various important organic compounds. In addition, many drugs and potential drug candidates contain α-aminocyanide structural fragments. Therefore, the efficient synthesis of α-aminonitrile compounds is of great significance for the subsequent synthesis of drugs and important organic compounds. Summary of the invention

[0003] The purpose of the present invention is to provide a method for synthesizing α-aminonitrile compounds, which has readily available raw materials, mild reaction conditions, good functional group compatibility, a wide range of substrate applications, and less pollution to the environment.

[0004] The present invention provides a method for synthesizing an α-aminonitrile compound, comprising: in an acidic solvent environment, under the action of a photocatalyst and a reducing agent, a fatty amine compound I, a fatty aldehyde / ketone compound II and a cyano group donor react under light to generate an α-aminonitrile compound III;

[0005]

[0006] Among them, R 1 is one of C1-C6 alkyl or cycloalkyl, tert-butyloxycarbonyl, benzyl or a substituted derivative thereof, R 2 is hydrogen, C1-C6 alkyl or cycloalkyl, tert-butyloxycarbonyl, benzyl or a substituted derivative thereof, R 3 is one of C1-C6 alkyl or cycloalkyl, phenyl, tert-butyloxycarbonyl, benzyl or one of its substituted derivatives or its substituted derivatives, R 4 It is one of hydrogen, C1-C6 alkyl or cycloalkyl, phenyl, tert-butyloxycarbonyl, benzyl or one of its substituted derivatives or its substituted derivatives.

[0007] Optionally, the solvent environment includes one of dimethyl sulfoxide, acetone, tetrahydrofuran, dimethylformamide, and dimethylacetamide.

[0008] Optionally, the solvent environment further includes an organic acid with a concentration of 0.01 mol / L-0.03 mol / L, and the organic acid includes one of propionic acid and p-toluenesulfonic acid.

[0009] The structural formula of the cyano donor is NC-R 5 , and R 5 It includes substituted or unsubstituted pyridyl or aryl groups; the cyano donor is preferably 4-cyanopyridine.

[0010] Optionally, the fatty amine compound I, the fatty aldehyde / ketone compound II and the cyano donor are reacted under mechanical mixing, and the mechanical mixing includes one of ultrasonic mixing, stirring mixing and oscillating mixing.

[0011] Optionally, the photocatalyst includes one of 4CzIPN, [Ir(dF(CF3)ppy)2(dtbbpy)]PF6, and Ru(bpy)3(PF6)2, and preferably the photocatalyst is 4CzIPN.

[0012] Optionally, the reducing agent includes one of Hantzsch ester, triethylamine, N,N-diisopropylethylamine, and 1-((trimethylsilyl)methyl)-piperidine. Preferably, the reducing agent is Hantzsch ester.

[0013] Optionally, the fatty amine compound I, the fatty aldehyde / ketone compound II and the cyano donor react under 450nm-480nm blue light.

[0014] Optionally, the fatty amine compound I, the fatty aldehyde / ketone compound II and the cyano donor are reacted under an LED light source with a power of 10W-50W.

[0015] Optionally, one or two of the fatty amine compound I, the fatty aldehyde / ketone compound II and the cyano donor are provided in excess.

[0016] Optionally, the molar ratio of the fatty amine compound I, the fatty aldehyde / ketone compound II and the cyano donor is 1:(1-2):(1-2).

[0017] Optionally, molecular sieves are also dispersed in the solvent environment, and the mass ratio of the molecular sieves to the photocatalyst is 100:(5-10).

[0018] Optionally, the molar ratio of the fatty amine compound I to the photocatalyst is (10-50):1.

[0019] Optionally, the mass ratio of the photocatalyst to the reducing agent is 1:(10-15).

[0020] Optionally, the reaction generates α-aminonitrile compound III and then quenching is carried out, and the pure α-aminonitrile compound III is obtained by extraction, rotary evaporation and column chromatography purification.

[0021] Optionally, the method comprises the following steps: in a protective atmosphere, stirring and mixing a reducing agent, a photocatalyst and a cyanide donor in an acidic solvent environment, and then adding aliphatic amine compound I and aliphatic aldehyde / ketone compound II and stirring and mixing to obtain a mixed solution; stirring and reacting the mixed solution under light, and then purifying the mixed solution to obtain an α-aminonitrile compound III. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 is the H NMR spectrum of the α-aminonitrile compound prepared in Example 1 of the present invention;

[0023] Figure 2 is the NMR carbon spectrum of the α-aminonitrile compound prepared in Example 1 of the present invention;

[0024] Figure 3 is the H NMR spectrum of the α-aminonitrile compound prepared in Example 2 of the present invention;

[0025] Figure 4 is the NMR carbon spectrum of the α-aminonitrile compound prepared in Example 2 of the present invention;

[0026] Figure 5 is the H NMR spectrum of the α-aminonitrile compound prepared in Example 3 of the present invention;

[0027] Figure 6 is the NMR carbon spectrum of the α-aminonitrile compound prepared in Example 3 of the present invention;

[0028] Figure 7 is the H NMR spectrum of the α-aminonitrile compound prepared in Example 4 of the present invention;

[0029] Figure 8 is the NMR carbon spectrum of the α-aminonitrile compound prepared in Example 4 of the present invention;

[0030] Fig. 9 is the H NMR spectrum of the α-aminonitrile compound prepared in Example 5 of the present invention;

[0031] Fig.10 is the NMR carbon spectrum of the α-aminonitrile compound prepared in Example 5 of the present invention;

[0032] Fig.11 is the H NMR spectrum of the α-aminonitrile compound prepared in Example 6 of the present invention;

[0033] Fig.12 This is the NMR carbon spectrum of the α-aminonitrile compound prepared in Example 6 of the present invention;

[0034] Fig.13 is the H NMR spectrum of the α-aminonitrile compound prepared in Example 7 of the present invention;

[0035] Fig.14 is the NMR carbon spectrum of the α-aminonitrile compound prepared in Example 7 of the present invention;

[0036] Fig.15 This is the NMR fluorine spectrum of the α-aminonitrile compound prepared in Example 7 of the present invention;

[0037] Fig.16 is the H NMR spectrum of the α-aminonitrile compound prepared in Example 8 of the present invention;

[0038] Fig.17 is the NMR carbon spectrum of the α-aminonitrile compound prepared in Example 8 of the present invention;

[0039] Fig.18 is the H NMR spectrum of the α-aminonitrile compound prepared in Example 9 of the present invention;

[0040] Fig.19 is the NMR carbon spectrum of the α-aminonitrile compound prepared in Example 9 of the present invention;

[0041] Fig. 20 is the H NMR spectrum of the α-aminonitrile compound prepared in Example 10 of the present invention;

[0042] Fig.21 is the NMR carbon spectrum of the α-aminonitrile compound prepared in Example 10 of the present invention;

[0043] Fig. 22 is the H NMR spectrum of the α-aminonitrile compound prepared in Example 11 of the present invention;

[0044] Fig.23 is the NMR carbon spectrum of the α-aminonitrile compound prepared in Example 11 of the present invention;

[0045] Fig.24 is the H NMR spectrum of the α-aminonitrile compound prepared in Example 12 of the present invention;

[0046] Fig.25 is the NMR carbon spectrum of the α-aminonitrile compound prepared in Example 12 of the present invention;

[0047] Fig.26 is the H NMR spectrum of the α-aminonitrile compound prepared in Example 13 of the present invention;

[0048] Fig. 27 is the NMR carbon spectrum of the α-aminonitrile compound prepared in Example 13 of the present invention;

[0049] Fig.28 is the H NMR spectrum of the α-aminonitrile compound prepared in Example 14 of the present invention;

[0050] Fig.29 is the NMR carbon spectrum of the α-aminonitrile compound prepared in Example 14 of the present invention;

[0051] Fig.30 is the H NMR spectrum of the α-aminonitrile compound prepared in Example 15 of the present invention;

[0052] Fig.31 is the NMR carbon spectrum of the α-aminonitrile compound prepared in Example 15 of the present invention;

[0053] Fig.32 The synthetic reaction formula of the α-aminonitrile compound provided by the present invention is:

[0054] Fig.33 The present invention provides a synthesis reaction mechanism diagram of an α-aminonitrile compound. DETAILED DESCRIPTION

[0055] In order to make the purpose, 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. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention. Unless otherwise defined, the technical terms or scientific terms used herein should be the common meanings understood by people with general skills in the field to which the present invention belongs.

[0056] The present invention provides a method for synthesizing α-aminonitrile compounds, comprising reacting aliphatic amine compounds I, aliphatic aldehyde / ketone compounds II and a cyano group donor under light in an acidic solvent environment under the action of a photocatalyst and a reducing agent to generate an α-aminonitrile compound III. In fact, under acidic conditions, the aliphatic amine compound I and the aliphatic aldehyde / ketone compound II undergo condensation to form an iminium cation, while on the other hand, the photocatalyst is excited under light and undergoes reduction quenching with the reducing agent to generate a reduced species, and the reduced species reduces the cyano group donor and releases a cyano group anion, and then the cyano group anion undergoes nucleophilic addition with the iminium cation to generate an α-aminonitrile compound III.

[0057] In fact, see Fig.32 The reaction formula for the reaction of fatty amine compound Ⅰ, fatty aldehyde / ketone compound Ⅱ and cyano donor to generate α-aminonitrile compound Ⅲ is:

[0058]

[0059] Among them, R 1 is one of C1-C6 alkyl or cycloalkyl, tert-butyloxycarbonyl, benzyl or a substituted derivative thereof, R 2 is hydrogen, C1-C6 alkyl or cycloalkyl, tert-butyloxycarbonyl, benzyl or a substituted derivative thereof, R 3 is one of C1-C6 alkyl or cycloalkyl, phenyl, tert-butyloxycarbonyl, benzyl or one of its substituted derivatives or its substituted derivatives, R 4 is one of hydrogen, C1-C6 alkyl or cycloalkyl, phenyl, tert-butyloxycarbonyl, benzyl or one of its substituted derivatives or its substituted derivatives. Specifically, the "substituted derivative" is the product of a hydrogen atom or atomic group in the original group being replaced by other atoms or atomic groups.

[0060] In fact, the synthesis method provided by the present invention, by using a solvent environment / photocatalyst / reducing agent as a reaction system, has good compatibility with the functional groups of the reactants, a wide range of substrate applications, and minimal pollution to the environment. It can be widely used in the synthesis of various drugs, functional materials and natural products in industry and academia.

[0061] In some embodiments, the solvent environment used includes one of dimethyl sulfoxide, acetone, tetrahydrofuran, dimethylformamide, and dimethylacetamide. In fact, the reaction rate can be effectively improved by promoting the uniform distribution of reactants in the solvent environment. In addition, the solvent environment also includes an organic acid with a concentration of 0.01mol / L-0.03mol / L, and the organic acid can create an acidic environment in the solvent environment to promote the reaction. Specifically, the organic acid includes one of propionic acid and p-toluenesulfonic acid.

[0062] In some embodiments, the structural formula of the cyano donor used is as follows:

[0063] NC-R 5

[0064] Among them, R 5 This includes substituted or unsubstituted pyridyl or aryl groups.

[0065] In practice, the cyano donor is preferably 4-cyanopyridine having the structural formula shown below:

[0066]

[0067] This can avoid the appearance of toxic cyanide in the reaction product, effectively improve the reaction safety and reduce the reaction cost.

[0068] In some embodiments, the fatty amine compound I, the fatty aldehyde / ketone compound II and the cyano donor are reacted under mechanical mixing, which can promote the uniform dispersion of the three reactants in the solvent environment, thereby effectively improving the reaction rate. Specifically, the mechanical mixing includes one of ultrasonic mixing, stirring mixing, and oscillating mixing.

[0069] In some embodiments, the photocatalyst used includes one of 4CzIPN, [Ir(dF(CF3)ppy)2(dtbbpy)]PF6, and Ru(bpy)3(PF6)2. Preferably, the photocatalyst can be 4CzIPN as shown in the following formula:

[0070]

[0071] In some embodiments, the reducing agent used includes one of Hantzsch ester, triethylamine, N,N-diisopropylethylamine, and 1-((trimethylsilyl)methyl)-piperidine. Preferably, the reducing agent can be a Hantzsch ester as shown in the following formula:

[0072]

[0073] In some embodiments, the fatty amine compound I, the fatty aldehyde / ketone compound II and the cyano group donor are reacted under 450nm-480nm blue light, which can promote the photocatalyst to effectively increase the reaction rate. Specifically, the reaction can be carried out under a LED light source with a power of 10W-50W.

[0074] Preferably, the fatty amine compound I, the fatty aldehyde / ketone compound II and the cyano donor are reacted under the irradiation of a 456 nm Kessil lamp. In addition, the Kessil lamp can be placed 2 cm to 10 cm above the top of the reaction solution for irradiation.

[0075] In some embodiments, one or two of the fatty amine compound I, the fatty aldehyde / ketone compound II and the cyano group donor are set in excess. Specifically, the molar ratio of the fatty amine compound I, the fatty aldehyde / ketone compound II and the cyano group donor is 1:(1-2):(1-2), thereby promoting the forward photocatalytic reaction and increasing the product yield.

[0076] In some embodiments, when the photocatalytic reaction is carried out under light, a molecular sieve is also dispersed in the solvent environment, and the mass ratio of the molecular sieve to the photocatalyst is 100:(5-10). In fact, the reaction rate can be further increased by adding the molecular sieve. In addition, the molar ratio of the fatty amine compound I to the photocatalyst is (10-50):1, and the mass ratio of the photocatalyst to the reducing agent is 1:(10-15).

[0077] In fact, the reaction generates α-aminonitrile compound III and then quenches, extracts, and evaporates the mixture, followed by column chromatography to obtain a pure α-aminonitrile compound III. Specifically, the reaction system can be quenched with a saturated sodium bicarbonate solution, extracted with ethyl acetate, and then the solvent is evaporated to obtain a crude α-aminonitrile compound III, which is then purified by column chromatography to obtain a pure α-aminonitrile compound III.

[0078] In some embodiments, the steps are included: in a protective atmosphere, a reducing agent, a photocatalyst and a cyanide donor are stirred and mixed in a solvent environment, and then a fatty amine compound I and a fatty aldehyde / ketone compound II are added and stirred to obtain a mixed solution; the mixed solution is stirred and reacted under light, and then purified to obtain an α-amino nitrile compound III.

[0079] Specifically, in an acidic solvent environment, 4CzIPN is used as a photocatalyst, Hantzsch ester is used as a reducing agent, and the reaction mechanism of aliphatic amine compound I, aliphatic aldehyde / ketone compound II and 4-cyanopyridine under blue light to generate α-aminonitrile compound III is as follows: Fig.33 As shown. Under acidic conditions, fatty amine compounds I and fatty aldehyde / ketone compounds II condense to form imine cation IV, while on the other hand, under blue light irradiation, the photocatalyst 4CzIPN is excited to produce 4CzIPN * , followed by reduction quenching with a Hantzsch ester to produce the reduced 4CzIPN · ￣, this species single-electron reduces 4-cyanopyridine to produce free radical VI, free radical VI couples with free radical intermediate VII to release cyanide anion, and finally the cyanide anion undergoes nucleophilic addition to imine cation IV to generate the product α-aminonitrile compound III.

[0080] Example 1

[0081] This embodiment 1 provides a method for synthesizing an α-aminonitrile compound, comprising the following steps:

[0082] S1. Add 0.30 mmol (31.3 mg) of 4-cyanopyridine and 0.30 mmol (76.0 mg) of Hantzsch ester into a reaction bottle, transfer it into a glove box filled with nitrogen, add 4.0 mg (2.5 mol%) of 4CzIPN photocatalyst and 100 mg of molecular sieve into the reaction bottle, add 2 mL of anhydrous dimethyl sulfoxide and stir to mix, take it out of the glove box and use a micro syringe to add 0.20 mmol (39.5 mg) of dibenzylamine, 0.30 mmol (40.5 mg) of phenylpropionaldehyde and 3.0 mg (20 mol%) of propionic acid into the reaction bottle, stir to mix to obtain a mixed solution;

[0083] S2. Use a light source with a power of 20 W and a light emission wavelength of 456 nm to irradiate the mixed solution at a position 4 cm from the top, and control the temperature of the mixed solution during the reaction process to be 25° C. Use a magnetic stirrer to vigorously stir the mixed solution at 500 rpm. After reacting for 8 hours, quench with a saturated sodium bicarbonate aqueous solution, extract with ethyl acetate, and concentrate with rotary evaporation to obtain a crude product, and purify the crude product by column chromatography to obtain an α-aminonitrile compound.

[0084] Example 2 to Example 15

[0085] Embodiments 2 to 15 of the present invention respectively provide a method for synthesizing an α-aminonitrile compound, which is different from Embodiment 1 in that the types of fatty amine compound I and fatty aldehyde / ketone compound II used in step S1 are different, as shown in Table 1 below.

[0086] Table 1

[0087]

[0088]

[0089]

[0090] The structural formula of the α-aminonitrile compound prepared in Example 1 is shown in the following formula III-1, and the calculated yield is 85%. The H-NMR spectrum of the compound is as follows: Figure 1 As shown, the NMR carbon spectrum characterization is as follows Figure 2 shown.

[0091]

[0092] 1 H NMR (400MHz, CDCl3) δ7.32–7.23(m,10H),7.17–7.11(m,3H),6.95–6.93(m,2H),3.94–3.90(m,2H ),3.59–3.54(m,1H),3.38–3.34(m,2H),2.75–2.68(m,1H),2.60–2.54(m,1H),2.11–1.98(m,1H). 13 C NMR (101MHz, CDCl3) δ140.16,137.91,129.03,128.80,128.72,128.46,127.79,126.46,117.60,55.70,52.34,33.20,31.95.

[0093] The structural formula of the α-aminonitrile compound prepared in Example 2 is shown in Formula III-2 below. The calculated yield is 90%. The H-NMR spectrum of the compound is as follows: Figure 3 As shown, the NMR carbon spectrum characterization is as follows Figure 4 shown.

[0094]

[0095] 1 H NMR (400MHz, CDCl3) δ7.35–7.29(m,5H),4.10(s,2H),3.94(d,J=13.7Hz,1H),3.56 (t,J=7.6Hz,1H),3.33(d,J=13.7Hz,1H),2.69–2.66(m,2H),2.40–2.38(m,2H),1.9 4(d,J=12.3Hz,1H),1.81–1.74(m,1H),1.65–1.52(m,4H),1.45(s,9H),1.09(dd,J =16.2,7.1Hz,1H),1.13–1.07(m,1H),0.83(d,J=6.6Hz,3H),0.73(d,J=6.4Hz,3H). 13 C NMR (101MHz, CDCl3) δ154.84,137.76,128.86,128.59,127.68,118.05,79.42,56. 90,56.81,51.76,44.04,40.41,34.32,30.59,30.47,28.48,24.40,22.44,21.71.

[0096] The structural formula of the α-aminonitrile compound prepared in Example 3 is shown in Formula III-3 below. The calculated yield is 90%. The compound was characterized by H NMR spectrum. Figure 5 As shown, the NMR carbon spectrum characterization is as follows Figure 6 shown.

[0097]

[0098] 1 H NMR (400MHz, CDCl3) δ7.84–7.82(m,2H),7.73–7.71(m,2H),7.34–7.21(m,10H),3.93(d,J=13.6Hz,2H),3.65(td,J=6.8,1.5Hz,2H ),3.54(dd,J=8.8,7.0Hz,1H),3.35(d,J=13.7Hz,2H),1.98–1.88(m,1H),1.83–1.74(m,1H),1.61–1.50(m,3H),1.42–1.32(m,1H). 13C NMR (101MHz, CDCl3) δ168.39,137.78,134.01,132.06,128.74,128.61,127.57,123.27,117.43,55.31,52.53,37.40,30.68,27.74,23.10.

[0099] The structural formula of the α-aminonitrile compound prepared in Example 4 is shown in Formula III-4 below. The calculated yield is 99%. The compound was characterized by H NMR spectrum as follows: Figure 7 As shown, the NMR carbon spectrum characterization is as follows Figure 8 shown.

[0100]

[0101] 1 H NMR (400MHz, CDCl3) δ7.32–7.28(m,2H),7.23–7.18(m,3H),7.16–7.10F(m,3H),7.04–7.02(m,1H), 3.86(d,J=14.4Hz,1H),3.67–3.57(m,2H),3.01–2.76(m,5H),2.71–2.65(m,1H),2.26–2.09(m,2H). 13 C NMR (101MHz, CDCl3) δ139.93,133.79,133.62,128.81,128.77,128.70,126.7 3,126.60,126.55,126.00,117.06,56.75,52.23,47.89,32.59,31.71,29.37.

[0102] The structural formula of the α-aminonitrile compound prepared in Example 5 is shown in Formula III-5 below. The calculated yield is 65%. The compound was characterized by H NMR spectrum. Fig. 9 As shown, the NMR carbon spectrum characterization is as follows Fig.10 shown.

[0103]

[0104] 1 H NMR (400MHz, CDCl3) δ7.33–7.18(m,7H),6.99(d,J=8.2Hz,1H),3.81(d,J=14.6Hz ,1H),3.63–3.56(m,2H),2.98–2.75(m,5H),2.69–2.64(m,1H),2.23–2.13(m,2H). 13CNMR(101MHz,CDCl3)δ139.72,135.76,132.76,130.42,129.60,129.47,128.7 5,128.62,126.60,119.45,116.82,56.48,51.73,47.53,32.47,31.62,28.85.

[0105] The structural formula of the α-aminonitrile compound prepared in Example 6 is shown in Formula III-6 below. The calculated yield is 95%. The compound was characterized by H NMR spectrum. Fig.11 As shown, the NMR carbon spectrum characterization is as follows Fig.12 shown.

[0106]

[0107] 1 H NMR (400MHz, CDCl3) δ7.34–7.24(m,10H),5.13(s,2H),4.48(s,2H),3.54–3 .47(m,7H),2.61(s,2H),2.38(s,2H),1.91–1.85(m,2H),1.78–1.72(m,2H). 13 C NMR (101MHz, CDCl3) δ155.08,138.31,136.62,128.61,128.51,128.18,128.01,1 27.77,127.72,116.77,73.01,69.08,67.32,57.55,49.35,43.53,27.80,26.01.

[0108] The structural formula of the α-aminonitrile compound prepared in Example 7 is shown in Formula III-7. The calculated yield is 79%. The H NMR spectrum of the compound is as follows: Fig.13 As shown, the NMR carbon spectrum characterization is as follows Fig.14 As shown, the NMR fluorine spectrum is as follows Fig.15 shown.

[0109]

[0110] 1H NMR (400MHz, CDCl3) δ7.36–7.33(m,4H),7.00–6.95(m,4H),4.22(s,1H),3.55(dd,J=8.8,7.1Hz,1H),2.73–2. 69(m,2H),2.51–2.42(m,5H),1.86–1.78(m,1H),1.70–1.63(m,1H),1.60–1.53F(m,1H),0.93(t,J=6.0Hz,6H). 13 CNMR(101MHz, CDCl3)δ163.09,160.65,138.05,129.27,117.30,115.61,115.40,74.25,56.07,51.34,39.48,24.87,22.35,22.06. 19 F NMR(376MHz, CDCl3)δ-115.54.(s,1F)ppm.

[0111] The structural formula of the α-aminonitrile compound prepared in Example 8 is shown in Formula III-8 below. The calculated yield is 92%. The H NMR spectrum of the compound is as follows: Fig.16 As shown, the NMR carbon spectrum characterization is as follows Fig.17 shown.

[0112]

[0113] 1 H NMR (400MHz, CDCl3) δ6.78–6.72(m,3H),5.95(s,2H),3.57(dd,J=8.3,7.2Hz,1H),2.96– 2.94(m,2H),2.72–2.67(m,2H),2.48–2.42(m,2H),1.71–1.60(m,6H),1.52–1.48(m,2H). 13 C NMR (101MHz, CDCl3) δ147.83,146.83,129.82,122.47,116.77,109.56,108.49,101.09,61.57,51.17,37.45,25.76,24.01.

[0114] The structural formula of the α-aminonitrile compound prepared in Example 9 is shown in Formula III-9 below. The calculated yield is 90%. The compound was characterized by H NMR spectrum. Fig.18 As shown, the NMR carbon spectrum characterization is as follows Fig.19 shown.

[0115]

[0116] 1 H NMR (400MHz, CDCl3) δ6.77–6.69(m,3H),5.94(s,2H),3.54(dd,J=8.8,6.7Hz,1H),3.03–2.92(m,4H),2.79–2.65(m,6H). 13 C NMR (101MHz, CDCl3) δ147.89,129.35,122.45,116.53,109.47,108.53,101.16,61.52,52.31,37.10,27.89.

[0117] The structural formula of the α-aminonitrile compound prepared in Example 10 is shown in Formula III-10. The calculated yield is 90%. The H NMR spectrum of the compound is as follows: Fig. 20 As shown, the NMR carbon spectrum characterization is as follows Fig.21 shown.

[0118]

[0119] 1 H NMR (400MHz, CDCl3) δ7.45–7.24(m,5H),6.78–6.69(m,3H),5.94(s,2H),5.14(s,2H),3.63(t,J= 7.8Hz,2H),3.54(ddd,J=13.2,9.0,3.8Hz,8H),2.95(d,J=7.8Hz,2H),2.71(s,2H),2.49(s,2H). 13 C NMR (101MHz, CDCl3) δ155.08,147.01,136.53,129.17,128.59,128.18,128.02,122.44,116.14,108.56,101.17,67.38,60.54.

[0120] The structural formula of the α-aminonitrile compound prepared in Example 11 is shown in Formula III-11. The calculated yield is 95%. The H-NMR spectrum of the compound is as follows: Fig. 22 As shown, the NMR carbon spectrum characterization is as follows Fig.23 shown.

[0121]

[0122] 1H NMR(400MHz, CDCl3)δ4.15(dr,2H),3.07(d,J=10.7Hz,1H),2.96–2.91(m,2H),2.76–2.66(m,8 H),1.96–1.83(m,3H),1.46(s,9H),1.20(qd,J=12.4,4.3Hz,1H),1.07(qd,J=12.4,4.3Hz,1H). 13 C NMR (101MHz, CDCl3) δ154.66,115.88,79.72,64.49,52.35,36.23,29.77,29.07,28.43,27.93.

[0123] The structural formula of the α-aminonitrile compound prepared in Example 12 is shown in Formula III-12. The calculated yield is 63%. The H-NMR spectrum of the compound is as follows: Fig.24 As shown, the NMR carbon spectrum characterization is as follows Fig.25 shown.

[0124]

[0125] 1 H NMR (400MHz, CDCl3) δ3.76–3.74(m,4H),2.65–2.63(m,4H),2.24–2.20(m,2H),1.88–1.85(m,4H),1.79–1.74(m,2H). 13 C NMR (101MHz, CDCl3) δ119.88,68.50,66.73,49.90,37.49,23.03.

[0126] The structural formula of the α-aminonitrile compound prepared in Example 13 is shown in Formula III-13. The calculated yield is 63%. The H NMR spectrum of the compound is as follows: Fig.26 As shown, the NMR carbon spectrum characterization is as follows Fig. 27 shown.

[0127]

[0128] 1 H NMR (400MHz, CDCl3) δ3.76–3.74(m,4H),2.66–2.64(m,4H),2.16–2.10(m,2H) ,1.84–1.76(m,2H),1.67–1.61(m,1H),1.58–1.50(m,4H),1.33–1.26(m,1H). 13C NMR (101MHz, CDCl3) δ118.99,67.00,61.16,47.06,33.55,24.93,22.08.

[0129] The structural formula of the α-aminonitrile compound prepared in Example 14 is shown in Formula III-14, and the calculated yield is 90%. The H NMR spectrum of the compound is as follows: Fig.28 As shown, the NMR carbon spectrum characterization is as follows Fig.29 shown.

[0130]

[0131] 1 H NMR (400MHz, CDCl3) δ7.35–7.25(m,5H),4.07(d,J=13.1Hz,1H),4.09–3.97(m,2H),3.81(d,J=13.1Hz,1H),3.40 –3.32(m,2H),3.29(d,J=7.3Hz,1H),1.93–1.82(m,2H),1.76–1.72(m,1H),1.58–1.48(m,2H),1.46–1.37(m,1H). 13 CNMR (101MHz, CDCl3) δ138.33,128.65,128.37,127.66,119.14,67.41,67.29,55.01,51.65,38.32,29.69,29.22.

[0132] The structural formula of the α-aminonitrile compound prepared in Example 15 is shown in Formula III-15, and the calculated yield is 90%. The H NMR spectrum of the compound is as follows: Fig.30 As shown, the NMR carbon spectrum characterization is as follows Fig.31 shown.

[0133]

[0134] 1 H NMR (400MHz, CDCl3) δ6.83–6.77(m,3H),3.89(s,3H),3.87(s,3H),3.02(t,J=6.9Hz,2H),2.79(t,J=6.9Hz ,2H),1.99(d,J=12.7Hz,2H),1.78–1.65(m,,3H),1.60–1.50(m,2H),1.47–1.40(m,3H),1.26–1.24(m,1H). 13C NMR (101MHz, CDCl3) δ148.98,147.59,131.42,122.06,120.64,111.61,111.25,57.27,55.91,55.87,44.76,36.05,36.05,35.59,25.13,22.34.

[0135] Although the embodiments of the present invention are described in detail above, it is obvious to those skilled in the art that various modifications and variations can be made to these embodiments. However, it should be understood that such modifications and variations are within the scope and spirit of the present invention as described in the claims. Moreover, the present invention described herein may have other embodiments and may be implemented or realized in a variety of ways.

Claims

1. A method for synthesizing an α-aminonitrile compound, characterized in that: include: In an acidic solvent environment, under the action of a photocatalyst and a reducing agent, aliphatic amine compounds Ⅰ, aliphatic aldehyde / ketone compounds Ⅱ and a cyanide donor react under light to generate α-aminonitrile compounds Ⅲ; Among them, R 1 is one of C1-C6 alkyl or cycloalkyl, tert-butyloxycarbonyl, benzyl or a substituted derivative thereof, R 2 is hydrogen, C1-C6 alkyl or cycloalkyl, tert-butyloxycarbonyl, benzyl or a substituted derivative thereof, R 3 is one of C1-C6 alkyl or cycloalkyl, phenyl, tert-butyloxycarbonyl, benzyl or one of its substituted derivatives or its substituted derivatives, R 4 It is one of hydrogen, C1-C6 alkyl or cycloalkyl, phenyl, tert-butyloxycarbonyl, benzyl or one of its substituted derivatives or its substituted derivatives.

2. The synthesis method according to claim 1, characterized in that: The solvent environment includes one of dimethyl sulfoxide, acetone, tetrahydrofuran, dimethylformamide, and dimethylacetamide; and / or the solvent environment also includes an organic acid with a concentration of 0.01 mol / L-0.03 mol / L, and the organic acid includes one of propionic acid and p-toluenesulfonic acid.

3. The synthesis method according to claim 1, characterized in that: The structural formula of the cyano donor is NC-R 5 , and R 5 It includes substituted or unsubstituted pyridyl or aryl groups; the cyano donor is preferably 4-cyanopyridine.

4. The synthesis method according to claim 1, characterized in that The fatty amine compound I, the fatty aldehyde / ketone compound II and the cyano group donor are reacted under mechanical mixing, wherein the mechanical mixing includes one of ultrasonic mixing, stirring mixing and oscillating mixing.

5. The synthesis method according to claim 1, characterized in that: The photocatalyst includes one of 4CzIPN, [Ir(dF(CF3)ppy)2(dtbbpy)]PF6, and Ru(bpy)3(PF6)2, and preferably the photocatalyst is 4CzIPN; and / or the reducing agent includes one of Hantzsch ester, triethylamine, N,N-diisopropylethylamine, and 1-((trimethylsilyl)methyl)-piperidine, and preferably the reducing agent is Hantzsch ester.

6. The synthesis method according to claim 1, characterized in that: The fatty amine compound I, the fatty aldehyde / ketone compound II and the cyano donor react under 450nm-480nm blue light; and / or, the fatty amine compound I, the fatty aldehyde / ketone compound II and the cyano donor react under a LED light source with a power of 10W-50W.

7. The synthesis method according to claim 1, characterized in that: One or two of the fatty amine compound I, the fatty aldehyde / ketone compound II and the cyano donor are arranged in excess; and / or the molar ratio of the fatty amine compound I, the fatty aldehyde / ketone compound II and the cyano donor is 1:(1-2):(1-2).

8. The synthesis method according to claim 1, characterized in that: When reacting under light, molecular sieves are also dispersed in the solvent environment, and the mass ratio of the molecular sieves to the photocatalyst is 100:(5-10); and / or the molar ratio of the fatty amine compound I to the photocatalyst is (10-50):1; and / or the mass ratio of the photocatalyst to the reducing agent is 1:(10-15).

9. The synthesis method according to claim 1, characterized in that The reaction generates α-aminonitrile compound III and then quenches. The pure α-aminonitrile compound III is obtained by extraction, rotary evaporation and column chromatography purification.

10. The synthesis method according to any one of claims 1 to 9, characterized in that: The following steps are included: In a protective atmosphere, a reducing agent, a photocatalyst and a cyanide donor are stirred and mixed in an acidic solvent environment, and then a fatty amine compound I and a fatty aldehyde / ketone compound II are added and stirred and mixed to obtain a mixed solution; the mixed solution is stirred and reacted under light, and then purified to obtain an α-aminonitrile compound III.

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