Industrial preparation method and application of high-purity alpha-aminonitrile

Abstract

The invention relates to an industrial preparation method and application of high-purity alpha-aminonitrile. The invention belongs to the technical field of fine chemical synthesis. The invention aims to solve the technical problems that the existing alpha-aminonitrile synthesis method is low in yield and purity, high in cost and not suitable for industrial production. According to the method disclosed by the invention, imine is taken as a substrate and reacts with acetone cyanohydrin under the action of ionic liquid to synthesize alpha-aminonitrile. According to the method disclosed by the invention, the nucleophilic addition cyanidation product of carbon-nitrogen double bonds is synthesized in one step at room temperature. The method has the advantages that the reaction process is greatly accelerated by selecting the ionic liquid and synergistically reasonably controlling the ratio of the substances, the efficient synthesis of the alpha-aminonitrile is realized, the purity of the alpha-aminonitrile is obviously improved, the substrate adaptability is good, and the method can be widely applied to the synthesis of the fields such as medicines in the industrial circle and the academic circle.

Description

Technical Field

[0001] The invention belongs to the technical field of fine chemical synthesis, and specifically relates to an industrial preparation method and application of high-purity α-aminonitrile. Background Art

[0002] α-aminonitrile is an important intermediate in the field of organic synthesis. It is widely used in the fields of chemistry and biology and can be used to synthesize a variety of amino acids, amides, diamines and nitrogen-containing heterocyclic compounds. Due to its excellent chemical and biological properties and the potential for chiral structure, α-aminonitrile can be used to synthesize antithrombotic drugs, anticancer drugs, etc. Therefore, studying the synthesis method of this type of compound is not only of great significance for organic synthesis methodology, but also has high potential value and research significance in the fields of medicine, biology, and materials science. The addition of unsaturated carbon-nitrogen double bonds using cyaniding agents is the main way to prepare α-aminonitrile. With the continuous deepening of research on this reaction, the selection of cyaniding agents is also being continuously optimized. Acetone cyanohydrin, as a by-product of acrylonitrile production, has entered the researchers' sight because of its low price, miscibility with water and a variety of organic solvents, and the only by-product after the reaction is acetone, which is suitable for industrial production. Compared with acetone cyanohydrin, hydrocyanic acid is more toxic and difficult to transport, causing greater harm to the environment and the health of researchers; although the toxicity of metal hydrides has been significantly reduced, they still have the problem of poor solubility in organic solvents; organic cyaniding reagents such as trimethylsilyl cyanide (TMSCN) have low atomic utilization, high prices, and are only suitable for small laboratory tests, not suitable for industrial production.

[0003] At present, the most direct way to prepare α-amino nitrile is the addition reaction of cyanide and carbon-nitrogen double bond, such as using trimethylsilyl cyanide as cyanide source, aldehyde and amine as raw materials to react in one pot to generate α-amino nitrile. However, this kind of method has the following problems: 1. Most of them adopt one-pot method, which has the problems of impure target product, residual aldehydes, easy to generate other by-products, complex operation, harsh conditions, and high purification difficulty; 2. Most of them use TMSCN as cyaniding reagent, which is widely favored for its high activity and low toxicity, but due to its expensive price and low atom economy, it is only suitable for laboratory tests and not suitable for industrial production; 3. It needs to add organic solvents, and most of them have high volatility, which is harmful to the environment and the health of operators; 4. The use of alkaline catalysts cannot be recycled and reused, which is harmful to the environment and the health of operators; 5. The reaction time of the reaction system using ionic liquids is long, and the substrate applicability is poor, the applicable range of amines is small, and fatty amines are not applicable. In view of the above problems, it is necessary to develop a green, safe, efficient and fast method for preparing α-amino nitrile. Summary of the invention

[0004] In order to overcome the above-mentioned deficiencies of the prior art, the present invention provides an industrial preparation method and application of high-purity α-aminonitrile.

[0005] The technical solution of the present invention is as follows:

[0006] One of the objects of the present invention is to provide an industrial preparation method of high-purity α-aminonitrile, which is carried out according to the following steps:

[0007] α-Aminonitrile was synthesized by using imine as substrate and reacting with acetone cyanohydrin in the presence of ionic liquid.

[0008] Further defined, the imine is N-benzylidenebenzylamine, N-benzyl-p-tolylmethylamine, N-benzyl-p-ethylphenylmethylamine, N-benzyl-p-chlorophenylmethylamine, N-benzyl-1-(furan-2-yl)methylamine, N-benzyl-1-(thiophen-2-yl)methylamine, N-benzyl-p-fluorophenylmethylamine, N-benzyl-p-isopropylphenylmethylamine, N-benzyl-1-(3-pyridyl)methylamine, N-benzyl-1-(2-pyridyl)methylamine, N-n-butyl-p-tolylmethylamine, N-benzyl-o-chlorophenylmethylamine, N-benzyl-m-chlorophenylmethylamine, N-benzyl-p-cyanophenylmethylamine, N-cyclohexyl-p-tolylmethylamine, N-cyclohexylmethyl-p-tolylmethylamine or N-1-(2-furanmethyl)-p-tolylmethylamine.

[0009] In a further embodiment, the ionic liquid is 1-butyl-3-methylimidazolium acetate, 1-butyl-3-methylimidazolium perchlorate, 1-ethyl-3-methylimidazolium acetate or 1-butyl-3-methylimidazolium bromide.

[0010] It is further defined that the amount of acetone cyanohydrin used is 1.0-2.0 times the equivalent of the imine, and the amount of ionic liquid used is 0.5-2.0 times the equivalent of the imine.

[0011] It is further defined that the amount of acetone cyanohydrin used is 1.5-2.0 times the equivalent of the imine, and the amount of ionic liquid used is 1.0-2.0 times the equivalent of the imine.

[0012] Most preferably, the amount of acetone cyanohydrin used is 1.5 times the equivalent of the ionic liquid.

[0013] It is further defined that the reaction temperature is 25-50°C.

[0014] The second object of the present invention is to provide an α-amino nitrile prepared by the above method, wherein the general structural formula of the α-amino nitrile is:

[0015]

[0016] In the formula, R1 represents phenyl, 4-Me-phenyl, 4-Et-phenyl, 4-Br-phenyl, 4-Cl-phenyl, 4-F-phenyl, 2-Cl-phenyl, 3-Cl-phenyl, 4-i-pr-phenyl, furanl, 4-methylbenzonitrile, 2-methylpyridine or 3-methylpyridine; R2 represents toluene, butane, cyclohexane, methylcyclohexane or 2-methylfuran.

[0017] It is further defined that the purity of the α-aminonitrile is greater than 99%.

[0018] The third object of the present invention is to provide an application of the above-mentioned α-aminonitrile as an intermediate in the fields of chemistry, biology and medicine.

[0019] Compared with the prior art, the present invention has the following advantages:

[0020] The method of the present invention starts from imine, uses cheap acetone cyanohydrin as a cyanide source, and under the action of green and pollution-free ionic liquid, no complicated operation is required, and the nucleophilic addition cyanidation product of the carbon-nitrogen double bond is synthesized in one step at room temperature. By selecting the ionic liquid and coordinating the reasonable control of the proportion of each substance, the reaction process is greatly accelerated, not only the efficient synthesis of α-amino nitrile is achieved, but also the purity of α-amino nitrile is significantly improved, and the purity of the obtained α-amino nitrile is greater than 99%. And no additional solvent is added, which is green, safe and recyclable. The method of the present invention has good substrate adaptability and can be widely used in the synthesis of medicines and other fields in industry and academia. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 is the infrared spectrum of 2-benzylamino-2-phenylacetonitrile prepared in Example 1;

[0022] Figure 2 2-benzylamino-2-phenylacetonitrile prepared in Example 1 1 HNMR spectrum. DETAILED DESCRIPTION

[0023] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0024] The experimental methods used in the following examples are conventional methods unless otherwise specified. The materials, reagents, methods and instruments used are conventional materials, reagents, methods and instruments in the art unless otherwise specified, and can be obtained through commercial channels by those skilled in the art.

[0025] The terms "comprising," "including," "having," "containing," or any other variations thereof, as used in the following examples, are intended to cover a non-exclusive inclusion. For example, a composition, step, method, article, or apparatus comprising the listed elements is not necessarily limited to only those elements, but may include other elements not expressly listed or inherent to such composition, step, method, article, or apparatus.

[0026] Example 1. Synthesis of 2-benzylamino-2-phenylacetonitrile.

[0027] At room temperature (25°C), add 500.0 mg of N-benzylidenebenzylamine, 0.35 mL of acetone cyanohydrin and 0.48 mL of 1-butyl-3-methylimidazole acetate to a round-bottom flask equipped with a magnetic stirrer. The reaction time is 20 min. Monitor the reaction by TLC. When the raw material disappears, wash with water first, then extract with dichloromethane, and then wash the organic phase with saturated brine. Dry with anhydrous magnesium sulfate and concentrate to obtain 2-benzylamino-2-phenylacetonitrile, 555.0 mg, light yellow oily liquid, with a yield of 97.5%, as shown in FIG. Figure 1 Shown is the infrared image of the cyanation product 2-benzylamino-2-phenylacetonitrile synthesized from the raw material N-benzylidenebenzylamine, with a purity of 99.4%.

[0028] like Figure 2 As shown, the product 2-benzylamino-2-phenylacetonitrile: 1 HNMR(400MHz,Chloroform-d)δ7.66~7.51(m,2H),7.50~7.42(m,4H),7.41(d,J=2.2Hz,1H),7.3 9(d,J=2.1Hz,1H),7.37(s,1H),7.36~7.29(m,1H),4.78(s,1H),4.24~3.87(m,2H),1.86(s,1H).

[0029] Example 2

[0030] The difference between this embodiment and embodiment 1 is that the ionic liquid used is replaced by 1-ethyl-3-methylimidazolium acetate from 1-butyl-3-methylimidazolium acetate. The other steps and parameters are the same as those in embodiment 1. The obtained product 2-benzylamino-2-phenylacetonitrile, 467.9 mg, light yellow oily liquid, yield 82.2%.

[0031] Example 3

[0032] The difference between this embodiment and embodiment 1 is that the ionic liquid used is replaced by 1-butyl-3-methylimidazole perchlorate instead of 1-butyl-3-methylimidazole acetate. The other steps and parameters are the same as those in embodiment 1. The obtained product 2-benzylamino-2-phenylacetonitrile, 401.3 mg, light yellow oily liquid, yield 70.5%.

[0033] Example 4

[0034] The difference between this embodiment and embodiment 1 is that the ionic liquid used is replaced by 1-butyl-3-methylimidazolium bromide instead of 1-butyl-3-methylimidazolium acetate. The other steps and parameters are the same as those in embodiment 1. The obtained product 2-benzylamino-2-phenylacetonitrile, 355.2 mg, light yellow oily liquid, yield 62.4%.

[0035] Example 5

[0036] The difference between this example and Example 1 is that the amount of the ionic liquid used is adjusted from 1-butyl-3-methylimidazolium acetate to 0.24 mL (0.5 equivalent of the substrate N-benzylidenebenzylamine). The other steps and parameters are the same as those in Example 1. The obtained product 2-benzylamino-2-phenylacetonitrile, 285.7 mg, light yellow oily liquid, yield 50.2%.

[0037] Example 6

[0038] The difference between this example and Example 1 is that the amount of the ionic liquid used is adjusted from 1-butyl-3-methylimidazolium acetate to 0.72 mL (1.5 equivalents of the substrate N-benzylidenebenzylamine). The other steps and parameters are the same as those in Example 1. The obtained product 2-benzylamino-2-phenylacetonitrile, 491.2 mg, light yellow oily liquid, yield 86.3%.

[0039] Example 7

[0040] The difference between this example and Example 1 is that the amount of the ionic liquid used is adjusted from 1-butyl-3-methylimidazolium acetate to 1.44 mL (2.0 equivalents of the substrate N-benzylidenebenzylamine). The other steps and parameters are the same as those in Example 1. The obtained product 2-benzylamino-2-phenylacetonitrile, 446.2 mg, light yellow oily liquid, yield 78.4%.

[0041] Example 8

[0042] The difference between this example and Example 1 is that the amount of acetone cyanohydrin used is adjusted to 0.12 mL (0.5 equivalent of the substrate N-benzylidenebenzylamine). The other steps and parameters are the same as those in Example 1. The obtained product 2-benzylamino-2-phenylacetonitrile, 258.4 mg, light yellow oily liquid, yield 45.4%.

[0043] Example 9

[0044] The difference between this example and Example 1 is that the amount of acetone cyanohydrin used is adjusted to 0.23 mL (1.0 equivalent of the substrate N-benzylidenebenzylamine). The other steps and parameters are the same as those in Example 1. The obtained product 2-benzylamino-2-phenylacetonitrile, 428.6 mg, light yellow oily liquid, yield 75.3%.

[0045] Example 10

[0046] The difference between this example and Example 1 is that the amount of acetone cyanohydrin used is adjusted to 0.46 mL (2.0 equivalents of the substrate N-benzylidenebenzylamine). The other steps and parameters are the same as those in Example 1. The obtained product 2-benzylamino-2-phenylacetonitrile, 494.1 mg, light yellow oily liquid, yield 86.8%.

[0047] Embodiment 11

[0048] The difference between this embodiment and embodiment 1 is that the reaction temperature is 30° C. The other steps and parameters are the same as those in embodiment 1. The obtained product 2-benzylamino-2-phenylacetonitrile, 445.5 mg, light yellow oily liquid, yield 78.3%.

[0049] Example 12

[0050] The difference between this embodiment and embodiment 1 is that the reaction temperature is 40° C. The other steps and parameters are the same as those in embodiment 1. The obtained product 2-benzylamino-2-phenylacetonitrile, 399.7 mg, light yellow oily liquid, yield 70.2%.

[0051] Embodiment 13

[0052] The difference between this example and Example 1 is that the reaction temperature is 50° C. The other steps and parameters are the same as those in Example 1. The obtained product 2-benzylamino-2-phenylacetonitrile, 339.2 mg, light yellow oily liquid, yield 59.6%.

[0053] Example 14: Synthesis of 2-benzylamino-2-tolueneacetonitrile

[0054] The difference between this example and Example 1 is that the substrate is replaced by N-benzylidenebenzylamine with N-benzyl-p-tolylmethylamine in an amount of 535.90 mg. The other steps and parameters are the same as those in Example 1. The obtained product 2-benzylamino-2-tolueneacetonitrile, 585.7 mg, light yellow oily liquid, yield 96.8%, purity 99.5%.

[0055] Product 2-benzylamino-2-tolueneacetonitrile: 1H NMR (300MHz, Chloroform-d) δ7.43~7.39(m,2H),7.39~7.35(m,2H),7.35~7.31(m,2H),7.31~7.25 (m,1H),7.21(s,1H),7.20~7.17(m,1H),4.70(s,1H),4.09~3.87(m,2H),2.35(s,3H),1.26(s,1H).

[0056] Example 15: Synthesis of 2-benzylamino-2-(4-ethylphenyl)acetonitrile

[0057] The difference between this example and Example 1 is that the substrate is replaced by N-benzylidenebenzylamine with N-benzyl-p-ethylphenylmethylamine in an amount of 571.65 mg. The other steps and parameters are the same as those in Example 1. The obtained product 2-benzylamino-2-(4-ethylphenyl)acetonitrile, 628.72 mg, light yellow oily liquid, yield 98.2%, purity 99.1%.

[0058] Product 2-benzylamino-2-(4-ethylphenyl)acetonitrile: 1 H NMR (300MHz, Chloroform-d) δ7.50~7.43(m,3H),7.43~7.39(m,2H),7.39~7.34(m,2H),7.33(q,J=1.9Hz,1H),7.2 8(s,1H),7.24(s,1H),4.74(s,1H),4.14~3.93(m,2H),2.68(q,J=7.6Hz,2H),1.27(d,J=7.6Hz,3H),1.23(s,1H).

[0059] Example 16: Synthesis of 2-benzylamino-2-(4-chlorophenyl)acetonitrile

[0060] The difference between this example and Example 1 is that the substrate is replaced by N-benzylidenebenzylamine with N-benzyl-p-chlorophenylmethylamine in an amount of 588.1 mg. The other steps and parameters are the same as those in Example 1. The obtained product 2-benzylamino-2-(4-chlorophenyl)acetonitrile, 625.02 mg, light yellow oily liquid, yield 95.1%, purity 99.7%.

[0061] Product 2-benzylamino-2-(4-chlorophenyl)acetonitrile: 1H NMR(300MHz,Chloroform-d)δ7.56~7.49(m,2H),7.42(d,J=3.9Hz,2H),7.40(q,J=2.1, 1.5Hz,2H),7.39~7.35(m,2H),7.32(m,1H),4.76(s,1H),4.12~3.92(m,2H),1.9(s,1H).

[0062] Example 17: Synthesis of 2-benzylamino-2-(2-furyl)acetonitrile

[0063] The difference between this example and Example 1 is that the substrate is replaced by N-benzylidenebenzylamine with N-benzyl-1-(furan-2-yl)methylamine in an amount of 474.19 mg. The other steps and parameters are the same as those in Example 1. The obtained product 2-benzylamino-2-(2-furanyl)acetonitrile, 521.63 mg, brown oily liquid, yield 96.1%, purity 99.2%.

[0064] Product 2-benzylamino-2-(2-furyl)acetonitrile: 1 H NMR(300MHz,Chloroform-d)δ8.22~7.42(m,2H),7.40(s,2H),7.36(d,J=7.4Hz,3 H),7.32(d,J=6.0Hz,1H),4.82(d,J=2.4Hz,1H),4.10~3.92(m,2H),1.62(s,1H).

[0065] Example 18: Synthesis of 2-benzylamino-2-(2-thienyl)acetonitrile

[0066] The difference between this example and Example 1 is that the substrate is replaced by N-benzylidenebenzylamine with N-benzyl-1-(thien-2-yl)methylamine in an amount of 515.30 mg. The other steps and parameters are the same as those in Example 1. The obtained product 2-benzylamino-2-(2-thienyl)acetonitrile, 568.70 mg, brown oily liquid, yield 97.3%, purity 99.6%.

[0067] Product 2-benzylamino-2-(2-thienyl)acetonitrile: 1 H NMR(300MHz,Chloroform-d)δ7.46(d,J=1.8Hz,1H),7.42(d,J=5.0Hz,2H),7.38(d,J=5.6Hz,2H) ,7.36(s,2H),7.33~7.29(m,1H),7.17~6.98(m,1H),4.98(s,1H),4.19~3.89(m,2H),1.31(s,1H).

[0068] Example 19: Synthesis of 2-benzylamino-2-(4-fluorophenyl)acetonitrile

[0069] The difference between this embodiment and embodiment 1 is that the substrate is replaced by N-benzylidenebenzylamine with N-benzyl-p-fluorophenylmethylamine in an amount of 545.95 mg. The other steps and parameters are the same as those in embodiment 1. The obtained product 2-benzylamino-2-(4-fluorophenyl)acetonitrile, 578.21 mg, light yellow oily liquid, yield 94.4%, purity 99.8%.

[0070] Product 2-benzylamino-2-(4-fluorophenyl)acetonitrile: 1HNMR (300MHz, Chloroform-d) δ7.55 (m, 1H), 7.47~7.40 (m, 2H), 7.38 (d, J=2.3Hz, 1H), 7.36 (d, J=1.7Hz, 1H), 7.32 (m, 1H), 7.21~7.06 (m, 2H), 4.75 (s, 1H), 4.20~3.89 (m, 2H), 1.28 (s, 1H).

[0071] Example 20: Synthesis of 2-benzylamino-2-(4-isopropylphenyl)acetonitrile

[0072] The difference between this example and Example 1 is that the substrate is replaced by N-benzylidenebenzylamine with N-benzyl-p-isopropylphenylmethylamine in an amount of 607.10 mg. The other steps and parameters are the same as those in Example 1. The obtained product 2-benzylamino-2-(4-isopropylphenyl)acetonitrile, 654.46 mg, light yellow oily liquid, yield 96.7%, purity 99.3%.

[0073] Product 2-benzylamino-2-(4-isopropylphenyl)acetonitrile: 1 HNMR (300MHz, Chloroform-d) δ7.51~7.45(m,2H),7.45~7.41(m,2H),7.41~7.36(m,2H),7.36~7.32(m,1H),7.30(d,J =3.4Hz,1H),7.27(s,1H),4.74(s,1H),4.15~3.94(m,2H),2.96(m,1H),1.33~1.29(m,1H),1.28(s,3H),1.26(s,3H).

[0074] Example 21: Synthesis of 2-benzylamino-2-(3-pyridyl)acetonitrile

[0075] The difference between this example and Example 1 is that the substrate is replaced by N-benzylidenebenzylamine with N-benzyl-1-(3-pyridyl)methylamine in an amount of 502.40 mg. The other steps and parameters are the same as those in Example 1. The obtained product 2-benzylamino-2-(3-pyridyl)acetonitrile, 544.16 mg, brown oily liquid, yield 95.2%, purity 99.6%.

[0076] Product 2-benzylamino-2-(3-pyridyl)acetonitrile: 1 H NMR (300MHz, Chloroform-d) δ8.87~8.60(m,2H),7.90(m,1H),7.44~7.39(m,3H),7.39~7.37(m,2H),7.3 6~7.34(m,1H),7.34~7.29(m,1H),4.81(s,1H),4.18~4.05(m,2H),3.98(d,J=13.0Hz,1H),1.27(s,1H).

[0077] Example 22: Synthesis of 2-benzylamino-2-(2-pyridyl)acetonitrile

[0078] The difference between this example and Example 1 is that the substrate is replaced by N-benzylidenebenzylamine with N-benzyl-1-(2-pyridyl)methylamine in an amount of 502.40 mg. The other steps and parameters are the same as those in Example 1. The obtained product 2-benzylamino-2-(2-pyridyl)acetonitrile, 551.02 mg, brown oily liquid, yield 96.4%, purity 99.7%.

[0079] Product 2-benzylamino-2-(2-pyridyl)acetonitrile: 1HNMR (300MHz, Chloroform-d) δ8.65 (m, 1H), 7.76 (m, 1H), 7.53~7.46 (m, 1H), 7.47~7.41 (m, 2H), 7.37 (m, 2H), 7.35~7.29 (m, 2H), 4.83 (s, 1H), 4.24~3.96 (m, 2H), 1.38~1.18 (m, 1H).

[0080] Example 23: Synthesis of 2-n-butylamino-2-tolueneacetonitrile

[0081] The difference between this example and Example 1 is that the substrate is replaced by N-butyl-p-tolylmethylamine in an amount of 448.81 mg. The other steps and parameters are the same as those in Example 1. The obtained product 2-n-butylamino-2-tolueneacetonitrile is 493.66 mg, brown liquid, with a yield of 95.3% and a purity of 99.5%.

[0082] Product 2-n-butylamino-2-tolueneacetonitrile: 1 HNMR(300MHz,Chloroform-d)δ7.38(d,J=2.0Hz,2H),7.22~7.15(m,2H),4.72(s ,1H),2.91~2.64(m,2H),2.34(s,3H),1.58~1.18(m,6H),0.91(t,J=7.3Hz,3H).

[0083] Example 24: Synthesis of 2-benzylamino-2-(2-chlorophenyl)acetonitrile

[0084] The difference between this example and Example 1 is that the substrate is replaced by N-benzylidenebenzylamine with N-benzyl o-chlorophenylmethylamine in an amount of 588.1 mg. The other steps and parameters are the same as those in Example 1. The obtained product 2-benzylamino-2-(2-chlorophenyl)acetonitrile, 634.21 mg, light yellow oily liquid, yield 96.5%, purity 99.3%.

[0085] Product 2-benzylamino-2-(2-chlorophenyl)acetonitrile: 1H NMR (300MHz, Chloroform-d) δ7.70~7.63 (m, 1H), 7.62~7.45 (m, 1H), 7.44 (d, J=1.8Hz, 1H), 7.41 (m, 2H), 7.39~7.37 (m, 2H), 7.36~7.29 (m, 2H), 5.07 (s, 1H), 4.22–3.92 (m, 2H), 1.98 (s, 1H).

[0086] Example 25: Synthesis of 2-benzylamino-2-(3-chlorophenyl)acetonitrile

[0087] The difference between this example and Example 1 is that the substrate is replaced by N-benzylidenebenzylamine with N-benzyl-m-chlorophenylmethylamine in an amount of 588.1 mg. The other steps and parameters are the same as those in Example 1. The obtained product 2-benzylamino-2-(3-chlorophenyl)acetonitrile, 640.14 mg, light yellow oily liquid, yield 97.4%, purity 99.4%.

[0088] Product 2-benzylamino-2-(3-chlorophenyl)acetonitrile: 1 HNMR(300MHz,Chloroform-d)δ7.58(m,1H),7.50~7.45(m,1H),7.44(s,1H),7.42(m ,2H),7.38(m,2H),7.37~7.29(m,2H),4.76(s,1H),4.15~3.93(m,2H),1.28(s,1H).

[0089] Example 26: Synthesis of 2-benzylamino-2-(3-cyanophenyl)acetonitrile

[0090] The difference between this example and Example 1 is that the substrate is replaced by N-benzylidenebenzylamine with N-benzyl-p-cyanophenylmethylamine in an amount of 563.92 mg. The other steps and parameters are the same as those in Example 1. The obtained product 2-benzylamino-2-(3-cyanophenyl)acetonitrile, 621.06 mg, light yellow oily liquid, yield 98.1%, purity 99.8%.

[0091] Product 2-benzylamino-2-(3-cyanophenyl)acetonitrile: 1HNMR (300MHz, Chloroform-d) δ7.73 (s, 4H), 7.41 (m, 2H), 7.39 (d, J = 0.9 Hz, 1H), 7.38-7.35 (m, 1H), 7.35-7.29 (m, 1H), 4.84 (s, 1H), 4.12-3.95 (m, 2H), 1.35-1.18 (m, 1H).

[0092] Example 27: Synthesis of 2-cyclohexylamino-2-tolueneacetonitrile

[0093] The difference between this example and Example 1 is that the substrate is replaced by N-cyclohexyl-p-tolylmethylamine, and the amount used is 515.49 mg. The other steps and parameters are the same as those in Example 1. The obtained product 2-cyclohexylamino-2-tolueneacetonitrile, 558.83 mg, light yellow oily liquid, yield 95.6%, purity 99.5%.

[0094] Product 2-cyclohexylamino-2-tolueneacetonitrile: 1H NMR (300MHz, Chloroform-d) δ7.46~7.39 (m, 2H), 7.22 (d, J=7.9Hz, 2H), 4.81 (s, 1H), 2.88 (m, 1H), 2.38 (s, 3H), 1.89~1.60 (m, 4H), 1.51~1.15 (m, 6H).

[0095] Example 28: Synthesis of 2-cyclohexylmethylamino-2-tolueneacetonitrile

[0096] The difference between this example and Example 1 is that the substrate is replaced by N-cyclohexylmethyl-p-tolylmethylamine, and the amount is 512.27 mg. The other steps and parameters are the same as those in Example 1. The obtained product 2-cyclohexylmethylamino-2-tolueneacetonitrile, 606.81 mg, yellow oily liquid, yield 97.8%, purity 99.7%.

[0097] Product 2-cyclohexylmethylamino-2-tolueneacetonitrile: 1HNMR (300MHz, Chloroform-d) δ7.46~7.40 (m, 2H), 7.22 (d, J=7.9Hz, 2H), 4.75 (s, 1H), 2.77~2.54 (m, 2H), 2.39 (s, 3H), 1.85~1.64 (m, 5H), 1.58~1.40 (m, 2H), 1.27~1.18 (m, 2H), 1.07~0.93 (m, 2H).

[0098] Example 29: Synthesis of 2-furanylmethylamino-2-tolueneacetonitrile

[0099] The difference between this example and Example 1 is that the substrate is replaced by N-1-(2-furanmethyl)-p-tolylmethylamine, and the amount used is 510.09 mg. The other steps and parameters are the same as those in Example 1. The obtained product 2-furanmethylamino-2-tolueneacetonitrile, 570.59 mg, yellow oily liquid, yield 98.5%, purity 99.3%.

[0100] Product 2-furanylmethylamino-2-tolueneacetonitrile: 1HNMR (300MHz, Chloroform-d) δ7.45~7.39 (m, 3H), 7.21 (s, 2H), 6.33 (m, 2H), 4.74 (s, 1H), 3.97 (d, J=1.7Hz, 2H), 2.38 (s, 3H).

[0101] Table 1 Example results

[0102]

[0103]

[0104] As can be seen from Examples 1 and 14-29, the method of the present invention starts from readily available imine, uses cheap and green acetone cyanohydrin as a cyanide source, and the ionic liquid is most preferably 1-butyl-3-methylimidazolium acetate, and the synthesis of imine nucleophilic addition cyanide is achieved quickly and efficiently at room temperature. The method has good compatibility with functional groups on aromatic rings and is a new type of green general synthesis method.

[0105] The above are only preferred specific embodiments of the present invention, which are all different implementations based on the overall concept of the present invention, and the protection scope of the present invention is not limited thereto. Any changes or substitutions that can be easily thought of by a person skilled in the art within the technical scope disclosed by the present invention should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention should be based on the protection scope of the claims.

Claims

1. An industrial preparation method of high-purity α-aminonitrile, characterized in that: The method: α-Aminonitrile was synthesized by using imine as substrate and reacting with acetone cyanohydrin in the presence of ionic liquid.

2. The method according to claim 1, characterized in that The imine is N-benzylidenebenzylamine, N-benzyl-p-tolylmethylamine, N-benzyl-p-ethylphenylmethylamine, N-benzyl-p-chlorophenylmethylamine, N-benzyl-1-(furan-2-yl)methylamine, N-benzyl-1-(thien-2-yl)methylamine, N-benzyl-p-fluorophenylmethylamine, N-benzyl-p-isopropylphenylmethylamine, N-benzyl-1-(3-pyridyl)methylamine, N-benzyl-1-(2-pyridyl)methylamine, N-n-butyl-p-tolylmethylamine, N-benzyl-o-chlorophenylmethylamine, N-benzyl-m-chlorophenylmethylamine, N-benzyl-p-cyanophenylmethylamine, N-cyclohexyl-p-tolylmethylamine, N-cyclohexylmethyl-p-tolylmethylamine or N-1-(2-furanmethyl)-p-tolylmethylamine.

3. The method according to claim 1, characterized in that The ionic liquid is 1-butyl-3-methylimidazolium acetate, 1-butyl-3-methylimidazolium perchlorate, 1-ethyl-3-methylimidazolium acetate or 1-butyl-3-methylimidazolium bromide.

4. The method according to claim 1, characterized in that: The amount of acetone cyanohydrin used is 1.0-2.0 times the equivalent of the imine, and the amount of ionic liquid used is 0.5-2.0 times the equivalent of the imine.

5. The method according to claim 4, characterized in that The amount of acetone cyanohydrin used is 1.5-2.0 times the equivalent of the imine, and the amount of ionic liquid used is 1.0-2.0 times the equivalent of the imine.

6. The method according to claim 5, characterized in that The amount of acetone cyanohydrin used is 1.5 times the equivalent of the ionic liquid.

7. The method according to claim 1, characterized in that The reaction temperature is 25-50°C.

8. The α-aminonitrile prepared by the method according to any one of claims 1 to 7, characterized in that The general structural formula of the α-aminonitrile is: In the formula, R1 represents phenyl, 4-Me-phenyl, 4-Et-phenyl, 4-Br-phenyl, 4-Cl-phenyl, 4-F-phenyl, 2-Cl-phenyl, 3-Cl-phenyl, 4-i-pr-phenyl, furanl, 4-methylbenzonitrile, 2-methylpyridine or 3-methylpyridine; R2 represents toluene, butane, cyclohexane, methylcyclohexane or 2-methylfuran.

9. The α-aminonitrile according to claim 8, characterized in that Purity>99%.

10. Use of the α-aminonitrile according to claim 8 or 9 as an intermediate in the fields of chemistry, biology and medicine.

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