Industrial preparation method and application of alpha-hydroxynitrile

Abstract

The invention relates to an industrial preparation method and application of alpha-hydroxynitrile. The invention belongs to the technical field of fine chemical synthesis. The invention aims to solve the technical problems of low yield, high cost and unsuitability for industrial production of the existing method for synthesizing alpha-hydroxynitrile. According to the method, the alpha-hydroxynitrile is synthesized through the reaction of aldehyde ketone carbonylate and acetone cyanohydrin under the action of the ionic liquid. According to the method disclosed by the invention, the green and high-yield synthesis of the alpha-hydroxynitrile is realized by selecting the ionic liquid and synergistically and reasonably controlling the ratio of the substances, and the possibility is provided for reducing the industrial production cost of the alpha-hydroxynitrile. The method is simple in experimental operation process, and can be widely applied to synthesis in the fields such as medicines in industrial and academic circles.

Description

Technical Field

[0001] The invention belongs to the technical field of fine chemical synthesis, and particularly relates to an industrial preparation method and application of alpha-hydroxynitrile. Background Art

[0002] α-Hydroxynitrile, also known as cyanohydrin, is a key intermediate in the chemical and pharmaceutical fields. This compound contains both cyano and hydroxyl groups, of which the cyano functional group can be smoothly converted into various functional groups such as amino, amide, aldehyde, carboxyl and ester groups, and the hydroxyl functional group can be smoothly converted into various functional groups such as carbonyl, carboxyl, ether and ester groups. In the modern synthetic chemistry system, cyanohydrin compounds occupy a pivotal position. As core intermediates for amination and multifunctional synthesis (including glycine, alanine, sodium sarcosinate, methionine, lactic acid, ethylenediaminetetraacetic acid, methyl methacrylate, azobisisobutyronitrile, etc.), they provide solid support for the research and development and production of many new materials and bioactive molecules.

[0003] Many patents have reported methods for the efficient preparation of α-hydroxy nitrile, but the cyaniding reagents used in the existing methods mostly focus on trimethylsilyl cyanide and metal cyanide. Both of these substances have the disadvantages of high price and low atomic utilization rate, and the use of trimethylsilyl cyanide as a cyaniding reagent will protect the hydroxyl group, and the trimethylsilyl group needs to be removed later. Secondly, these methods generally require additional solvents, most of which are organic solvents. Although organic solvents show excellent solubility for organic compounds, their potential harm to human health cannot be ignored, and most organic solvents are volatile, which poses a threat to the atmospheric environment. Another part of the method chooses water as a solvent. However, due to the hydrophobic properties of organic substrates in water, the catalytic efficiency of some catalysts in water is significantly reduced, and water-sensitive substrates cannot react effectively in an aqueous environment. Furthermore, the required alkaline catalyst is unstable in nature, the recovery and post-processing process is complicated, and it has a negative impact on the environment. Therefore, from the perspective of environmental protection and sustainable development, exploring methods for preparing α-hydroxy nitrile not only has important theoretical value, but also has broad practical application prospects. 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 α-hydroxynitrile.

[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 α-hydroxynitrile, which is carried out according to the following steps:

[0007] α-Hydroxynitrile was synthesized by the reaction of aldehydes and ketones carbonyls with acetone cyanohydrin in the presence of ionic liquid.

[0008] It is further defined that the aldehyde and ketone carbonyl compounds are phenylacetaldehyde, phenylpropionaldehyde, butyraldehyde, valeraldehyde, hexanal, 2-methylvaleraldehyde, isovaleraldehyde, 2-pentanone, 3-pentanone, 3-methylbutanone, pinacolone, 4-heptanone, 5-methylhexanone, 5-chloro-2-pentanone or cyclohexanone.

[0009] In a further embodiment, the ionic liquid is 1-butyl-3-methylimidazolium trifluoroacetate, 1-ethyl-3-methylimidazolium trifluoroacetate or 1-butyl-3-methylimidazolium dinitrile amine salt.

[0010] It is further defined that the amount of acetone cyanohydrin used is 1.0-4.0 times the equivalent of the aldehyde or ketone carbonyl compound, and the amount of ionic liquid used is 2.0-4.0 times the equivalent of the aldehyde or ketone carbonyl compound.

[0011] It is further defined that the amount of acetone cyanohydrin used is 2.0-3.0 times the equivalent of the aldehyde or ketone carbonyl compound, and the amount of ionic liquid used is 2.0-3.0 times the equivalent of the aldehyde or ketone carbonyl compound.

[0012] Most preferably, the amount of acetone cyanohydrin used is 1.0 equivalent of the ionic liquid.

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

[0014] It is further defined that after the reaction is completed, washing with water, extracting the organic phase and concentrating are performed in sequence.

[0015] The second object of the present invention is to provide an α-hydroxynitrile prepared by the above method, wherein the general structural formula of the α-hydroxynitrile is:

[0016]

[0017] In the formula, R1 represents 1-Me-ph-, 1-Et-ph-, Me-, Et-, m-Bu-, i-Bu-, t-Bu-, m-pr-, i-pr- or 3-cl-m-pr-; R2 represents H-, Me-, Et- or m-pr-.

[0018] The third object of the present invention is to provide an application of the above-mentioned α-hydroxynitrile as an intermediate in the chemical and pharmaceutical fields.

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

[0020] The method of the present invention starts from aldehyde and ketone carbonyl compounds, respectively uses cheap acetone cyanohydrin as a cyanide source, and under the action of green, pollution-free and recyclable ionic liquids, alpha-hydroxy nitrile is efficiently synthesized under heating conditions without complicated water anaerobic operation. By selecting the ionic liquid and coordinating the reasonable control of the proportion of each substance, the green high-yield synthesis of alpha-hydroxy nitrile is achieved, which provides a possibility for reducing the industrial production cost of alpha-hydroxy nitrile. Compared with the conventional alpha-hydroxy nitrile synthesis method, the method of the present invention has the advantages of cheap and easy availability of reaction raw materials, acetone cyanohydrin is used as a cyanide source, and highly toxic substances such as hydrocyanic acid are replaced, and the scope of application is wide, the experimental operation process is simple, and it can be widely used in the synthesis of medicines and other fields in industry and academia. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 The 2-hydroxy-3-phenylpropionitrile obtained in Example 1 1 HNMR spectrum. DETAILED DESCRIPTION

[0022] 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.

[0023] 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.

[0024] 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.

[0025] Example 1: Synthesis of 2-hydroxy-3-phenylpropionitrile.

[0026] 0.19 mL of phenylacetaldehyde was added to a flask equipped with a rotor, and 0.45 mL of acetone cyanohydrin and 0.93 mL of 1-butyl-3-methylimidazole dinitrile amine salt were added dropwise to the reaction system in sequence, and stirred at room temperature (25°C). The reaction time was 0.5 h. The reaction was monitored by thin layer chromatography combined with potassium permanganate colorimetry. After the substrate reaction was complete, deionized water was added, and the system was extracted with ethyl acetate. The organic phase was washed with water and saturated brine respectively, dried with anhydrous MgSO4, filtered and concentrated to obtain 2-hydroxy-3-phenylpropionitrile, 143.4 mg, colorless oily liquid, with a yield of 97.4%.

[0027] Product 2-hydroxy-3-phenylpropionitrile: 1 H NMR(300MHz,Chloroform-d)δ7.39(d,J=1.8Hz,1H),7.36(dt,J=3.6,1.6Hz,2H),7.34–7.3 0(m,2H),7.29(d,J=1.7Hz,1H),4.60(t,J=6.8Hz,1H),3.76(s,1H),3.10(d,J=6.7Hz,2H).

[0028] Example 2

[0029] The difference between this embodiment and embodiment 1 is that the ionic liquid used is replaced by 1-butyl-3-methylimidazolium dinitrile amine salt with 1-butyl-3-methylimidazolium trifluoroacetate. The other steps and parameters are the same as those in embodiment 1. The obtained product 2-hydroxy-3-phenylpropionitrile, 124.1 mg, colorless oily liquid, yield 84.3%.

[0030] Example 3

[0031] The difference between this embodiment and embodiment 1 is that the ionic liquid used is replaced by 1-butyl-3-methylimidazolium dinitrile amine salt with 1-butyl-3-methylimidazolium tetrafluoroborate. The other steps and parameters are the same as those in embodiment 1. The obtained product 2-hydroxy-3-phenylpropionitrile, 61.7 mg, colorless oily liquid, yield 41.9%.

[0032] Example 4

[0033] The difference between this embodiment and embodiment 1 is that the ionic liquid used is replaced by 1-ethyl-3-methylimidazolium trifluoroacetate instead of 1-butyl-3-methylimidazolium dinitrile amine salt. The other steps and parameters are the same as those in embodiment 1. The obtained product 2-hydroxy-3-phenylpropionitrile, 109.5 mg, colorless oily liquid, yield 79.8%.

[0034] Example 5

[0035] The difference between this example and Example 1 is that the ionic liquid used is replaced by 1-butyl-3-methylimidazole dinitrile amine salt with 1-butyl-3-methylimidazole p-toluenesulfonate. The other steps and parameters are the same as those in Example 1. The obtained product 2-hydroxy-3-phenylpropionitrile, 48.0 mg, colorless oily liquid, yield 35.0%.

[0036] Example 6

[0037] The difference between this embodiment and embodiment 1 is that the amount of ionic liquid used is adjusted from 1-butyl-3-methylimidazole dinitrile amine salt to 0.31 mL (1.0 equivalent of substrate phenylpropanaldehyde). Other steps and parameters are the same as those in embodiment 1. The obtained product 2-hydroxy-3-phenylpropionitrile, 44.8 mg, colorless oily liquid, yield 32.7%.

[0038] Example 7

[0039] The difference between this embodiment and embodiment 1 is that the amount of ionic liquid used is adjusted from 1-butyl-3-methylimidazole dinitrile amine salt to 0.62 mL (2.0 equivalents of substrate phenylpropanaldehyde). Other steps and parameters are the same as those in embodiment 1. The obtained product 2-hydroxy-3-phenylpropionitrile, 118.9 mg, colorless oily liquid, yield 86.7%.

[0040] Example 8

[0041] The difference between this embodiment and embodiment 1 is that the amount of ionic liquid used is adjusted from 1-butyl-3-methylimidazole dinitrile amine salt to 1.24 mL (4.0 amount of substrate phenylpropanaldehyde). Other steps and parameters are the same as those in embodiment 1. The obtained product 2-hydroxy-3-phenylpropionitrile, 91.5 mg, colorless oily liquid, yield 66.7%.

[0042] Example 9

[0043] The difference between this example and Example 1 is that the amount of acetone cyanohydrin used is adjusted to 0.15 mL (1.0 equivalent of the substrate phenylpropanaldehyde). The other steps and parameters are the same as those in Example 1. The obtained product 2-hydroxy-3-phenylpropionitrile, 93.4 mg, colorless oily liquid, yield 68.1%.

[0044] Example 10

[0045] The difference between this example and Example 1 is that the amount of acetone cyanohydrin used is adjusted to 0.30 mL (2.0 equivalents of the substrate phenylpropanaldehyde). The other steps and parameters are the same as those in Example 1. The obtained product 2-hydroxy-3-phenylpropionitrile, 115.5 mg, colorless oily liquid, yield 84.2%.

[0046] Embodiment 11

[0047] The difference between this example and Example 1 is that the amount of acetone cyanohydrin used is adjusted to 0.60 mL (4.0 equivalents of the substrate phenylpropanaldehyde). The other steps and parameters are the same as those in Example 1. The obtained product 2-hydroxy-3-phenylpropionitrile, 1001.0 mg, colorless oily liquid, yield 73.6%.

[0048] Example 12

[0049] 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-hydroxy-3-phenylpropionitrile, 119.8 mg, colorless oily liquid, yield 87.3%.

[0050] Embodiment 13

[0051] 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-hydroxy-3-phenylpropionitrile, 99.3 mg, colorless oily liquid, yield 72.4%.

[0052] Embodiment 14

[0053] The difference between this embodiment and embodiment 1 is that the reaction temperature is 50° C. The other steps and parameters are the same as those in embodiment 1. The obtained product 2-hydroxy-3-phenylpropionitrile, 71.2 mg, colorless oily liquid, yield 51.9%.

[0054] Example 15: Synthesis of 2-hydroxy-4-phenylbutyronitrile.

[0055] The difference between this embodiment and embodiment 1 is that the amount of the ionic liquid used is adjusted from 1-butyl-3-methylimidazole dinitrile amine salt to 0.56 mL, the amount of acetone cyanohydrin is adjusted to 0.41 mL, and the reaction substrate is 0.20 mL of phenylpropanaldehyde. The other steps and parameters are the same as those in embodiment 1. The obtained product 2-hydroxy-4-phenylbutyronitrile, 232.7 mg, colorless oily liquid, yield 96.9%.

[0056] Product 2-hydroxy-4-phenylbutyronitrile: 1 H NMR (300MHz, Chloroform-d) δ7.32(d,J=14.2Hz,2H),7.25–7.18(m,3H),4.41(t,J=6.8Hz,1H),3.16(s,1H),2.84(t,J=8.1Hz,2H),2.22–2.11(m,2H).

[0057] Example 16: Synthesis of 2-hydroxyvaleronitrile.

[0058] The difference between this embodiment and embodiment 1 is that the amount of ionic liquid used is adjusted from 1-butyl-3-methylimidazole dinitrile amine salt to 1.05 mL, the amount of acetone cyanohydrin is adjusted to 0.76 mL, and the reaction substrate is 0.24 mL of butyraldehyde. The other steps and parameters are the same as those in embodiment 1. The obtained product 2-hydroxyvaleronitrile, 263.9 mg, colorless oily liquid, yield 96.1%.

[0059] Product 2-hydroxyvaleronitrile: 1 H NMR (300MHz, Chloroform-d) δ7.32(d,J=14.2Hz,2H),7.25–7.18(m,3H),4.41(t,J=6.8Hz,1H),3.16(s,1H),2.84(t,J=8.1Hz,2H),2.22–2.11(m,2H).

[0060] Example 17: Synthesis of 2-hydroxyhexanenitrile.

[0061] The difference between this embodiment and embodiment 1 is that the amount of the ionic liquid used is adjusted from 1-butyl-3-methylimidazole dinitrile amine salt to 1.05 mL, the amount of acetone cyanohydrin is adjusted to 0.76 mL, and the reaction substrate is 0.25 mL of valeraldehyde. The other steps and parameters are the same as those in embodiment 1. The obtained product 2-hydroxyhexanenitrile, 251.5 mg, colorless oily liquid, yield 95.9%.

[0062] Product 2-hydroxyhexanenitrile: 1 H NMR (300MHz, Chloroform-d) δ4.44(d,J=7.2Hz,1H),2.62(s,1H),1.80(d,J=7.3Hz,2H),1.58–1.31(m,4H),0.92(t,J=7.1Hz,3H).

[0063] Example 18: Synthesis of 2-hydroxyheptanenitrile.

[0064] The difference between this example and Example 1 is that the amount of the ionic liquid used is adjusted from 1-butyl-3-methylimidazole dinitrile amine salt to 0.76 mL, the amount of acetone cyanohydrin is adjusted to 0.55 mL, and the reaction substrate is 0.25 mL of hexanal. The other steps and parameters are the same as those in Example 1. The obtained product 2-hydroxyheptanenitrile, 194.2 mg, colorless oily liquid, yield 96.5%.

[0065] Product 2-hydroxyheptanenitrile: 1H NMR (300MHz, Chloroform-d) δ4.44(d,J=7.2Hz,1H),2.62(s,1H),1.80(d,J=7.3Hz,2H),1.58–1.31(m,4H),0.92(t,J=7.1Hz,3H).

[0066] Example 19: Synthesis of 2-hydroxy-3-methylhexanenitrile.

[0067] The difference between this embodiment and embodiment 1 is that the amount of ionic liquid used is adjusted from 1-butyl-3-methylimidazole dinitrile amine salt to 0.76 mL, the amount of acetone cyanohydrin is adjusted to 0.55 mL, and the reaction substrate is 0.25 mL of 2-methylvaleraldehyde. The other steps and parameters are the same as those in embodiment 1. The obtained product 2-hydroxy-3-methylhexanenitrile, 243.5 mg, colorless oily liquid, yield 95.2%.

[0068] Product 2-hydroxy-3-methylhexanenitrile: 1 H NMR (300MHz, Chloroform-d) δ2.64 (s, 1H), 1.77–1.73 (m, 1H), 1.61 (d, J = 13.2Hz, 4H), 1.45 (m, 1H), 0.95 (s, 3H), 0.93 (s, 3H).

[0069] Example 20: Synthesis of 2-hydroxy-4-methylvaleronitrile.

[0070] The difference between this embodiment and embodiment 1 is that the amount of the ionic liquid used is adjusted from 1-butyl-3-methylimidazole dinitrile amine salt to 0.88 mL, the amount of acetone cyanohydrin is adjusted to 0.63 mL, and the reaction substrate is 0.25 mL of isovaleraldehyde. The other steps and parameters are the same as those in embodiment 1. The obtained product 2-hydroxy-3-methylhexanenitrile, 248.4 mg, colorless oily liquid, yield 94.6%.

[0071] Product 2-hydroxy-3-methylhexanenitrile: 1 HNMR(300MHz,Chloroform-d)δ4.55–4.44(m,1H),3.67(s,1H),1.88(m,1H),1.80–1.62(m,2H),0.96(d,J=6.5Hz,6H).

[0072] Example 21. Synthesis of 2-hydroxy-2-methylvaleronitrile.

[0073] The difference between this embodiment and embodiment 1 is that the amount of the ionic liquid used is adjusted from 1-butyl-3-methylimidazole dinitrile amine salt to 0.88 mL, the amount of acetone cyanohydrin is adjusted to 0.63 mL, and the reaction substrate is 0.25 mL of 2-pentanone. The other steps and parameters are the same as those in embodiment 1. The obtained product 2-hydroxy-2-methylvaleronitrile, 247.6 mg, colorless oily liquid, yield 94.3%.

[0074] Product 2-hydroxy-2-methylvaleronitrile: 1 H NMR (300MHz, Chloroform-d) δ3.79 (s, 1H), 1.76–1.66 (m, 2H), 1.56 (s, 1H), 1.55–1.41 (m, 2H), 0.96 (t, J = 7.2Hz, 3H).

[0075] Example 22: Synthesis of 2-ethyl-2-hydroxybutyronitrile.

[0076] The difference between this embodiment and embodiment 1 is that the amount of the ionic liquid used is adjusted from 1-butyl-3-methylimidazole dinitrile amine salt to 0.88 mL, the amount of acetone cyanohydrin is adjusted to 0.63 mL, and the reaction substrate is 0.25 mL of 3-pentanone. The other steps and parameters are the same as those in embodiment 1. The obtained product 2-ethyl-2-hydroxybutyronitrile, 246.5 mg, colorless oily liquid, yield 93.9%.

[0077] Product 2-ethyl-2-hydroxybutyronitrile: 1 H NMR (300MHz, Chloroform-d) δ3.75 (s, 1H), 1.74 (m, 4H), 1.04 (t, J = 7.5Hz, 6H).

[0078] Example 23: Synthesis of 2-hydroxy-2,3-dimethylbutyronitrile.

[0079] The difference between this embodiment and embodiment 1 is that the amount of the ionic liquid used is adjusted from 1-butyl-3-methylimidazole dinitrile amine salt to 0.88 mL, the amount of acetone cyanohydrin is adjusted to 0.63 mL, and the reaction substrate is 0.25 mL of 3-methylbutanone. The other steps and parameters are the same as those in embodiment 1. The obtained product 2-hydroxy-2,3-dimethylbutyronitrile, 245.7 mg, colorless oily liquid, yield 93.6%.

[0080] Product 2-hydroxy-2,3-dimethylbutyronitrile: 1 H NMR (300MHz, Chloroform-d) δ3.15 (s, 1H), 1.91 (sep, J=6.8Hz, 1H), 1.55 (s, 3H), 1.07 (dd, J=10.3, 6.8Hz, 6H).

[0081] Example 24: Synthesis of 2-hydroxy-2,3,3-trimethylbutyronitrile.

[0082] The difference between this embodiment and embodiment 1 is that the amount of the ionic liquid used is adjusted from 1-butyl-3-methylimidazole dinitrile amine salt to 0.88 mL, the amount of acetone cyanohydrin is adjusted to 0.63 mL, and the reaction substrate is 0.25 mL of pinacolone. The other steps and parameters are the same as those in embodiment 1. The obtained product 2-hydroxy-2,3,3-trimethylbutyronitrile, 276.8 mg, white solid, yield 93.8%.

[0083] Product 2-hydroxy-2,3,3-trimethylbutyronitrile: 1 H NMR(300MHz,Chloroform-d)δ1.59(s,3H),1.30(s,1H),1.12(s,9H).

[0084] Example 25. Synthesis of 2-hydroxy-2-propylvaleronitrile.

[0085] The difference between this embodiment and embodiment 1 is that the amount of the ionic liquid used is adjusted from 1-butyl-3-methylimidazole dinitrile amine salt to 0.66 mL, the amount of acetone cyanohydrin is adjusted to 0.48 mL, and the reaction substrate is 0.24 mL of 4-heptanone. The other steps and parameters are the same as those in embodiment 1. The obtained product 2-hydroxy-2-propyl valeronitrile, 235.0 mg, colorless oily liquid, yield 95.1%.

[0086] Product 2-hydroxy-2-propylvaleronitrile: 1 H NMR (300MHz, Chloroform-d) δ3.48 (s, 1H), 1.76–1.61 (m, 4H), 1.61–1.41 (m, 4H), 0.94 (t, J = 7.2Hz, 6H).

[0087] Example 26: Synthesis of 2-hydroxy-2,5-dimethylhexanenitrile.

[0088] The difference between this embodiment and embodiment 1 is that the amount of the ionic liquid used is adjusted from 1-butyl-3-methylimidazole dinitrile amine salt to 0.66 mL, the amount of acetone cyanohydrin is adjusted to 0.48 mL, and the reaction substrate is 0.24 mL of 5-methylhexanone. The other steps and parameters are the same as those in embodiment 1. The obtained product 2-hydroxy-2,5-dimethylhexanenitrile, 234.1 mg, colorless oily liquid, yield 94.7%.

[0089] Product 2-hydroxy-2,5-dimethylhexanenitrile: 1H NMR (300MHz, Chloroform-d) δ3.93(s,1H),1.75–1.64(m,2H),1.64–1.53(m,1H),1.46–1.22(m,2H),0.88(s,3H),0.86(s,3H).

[0090] Example 27. Synthesis of 5-chloro-2-hydroxy-2-methylvaleronitrile.

[0091] The difference between this embodiment and embodiment 1 is that the amount of the ionic liquid used is adjusted from 1-butyl-3-methylimidazole dinitrile amine salt to 0.62 mL, the amount of acetone cyanohydrin is adjusted to 0.45 mL, and the reaction substrate is 0.19 mL of 5-chloro-2-pentanone. The other steps and parameters are the same as those in embodiment 1. The obtained product 5-chloro-2-hydroxy-2-methylvaleronitrile, 234.5 mg, orange-yellow oily liquid, yield 95.7%.

[0092] Product 5-chloro-2-hydroxy-2-methylvaleronitrile: 1 HNMR(300MHz,Chloroform-d)δ3.89(s,1H),3.63–3.54(m,2H),2.10–1.93(m,2H),1.91(m,1H),1.88(dd,J=7.3,2.4Hz,1H),1.59(s,3H).

[0093] Example 28. Synthesis of 1-hydroxycyclohexane-1-carbonitrile.

[0094] The difference between this embodiment and embodiment 1 is that the amount of the ionic liquid used is adjusted from 1-butyl-3-methylimidazole dinitrile amine salt to 0.79 mL, the amount of acetone cyanohydrin is adjusted to 0.56 mL, and the reaction substrate is 0.21 mL of cyclohexanone. The other steps and parameters are the same as those in embodiment 1. The obtained product 1-hydroxycyclohexane-1-carbonitrile, 234.5 mg, orange-yellow oily liquid, yield 95.3%.

[0095] Product 1-hydroxycyclohexane-1-carbonitrile: 1 HNMR(300MHz,Chloroform-d)δ4.41–4.18(s,1H),2.05(dd,J=11.2,7.7Hz,2H),1.75(m,2H),1.67–1.42(m,5H),1.24(m,1H).

[0096] Table 1 Example results

[0097]

[0098]

[0099] From Examples 1, 15-28, it can be seen that the method of the present invention starts from readily available aliphatic aldehyde ketone carbonyl compounds, uses cheap and low-toxic acetone cyanohydrin as a cyanide source, and the ionic liquid is most preferably 1-butyl-3-methylimidazolium dinitrile amine salt. Under a heating element, the aldehyde ketone carbonyl compound is efficiently subjected to a nucleophilic addition reaction to generate α-hydroxy nitrile. The method has good compatibility for changing the functional groups on both sides of the carbonyl group, and is a new type of green general synthesis method.

[0100] 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 α-hydroxynitrile, characterized in that: The method: α-Hydroxynitrile was synthesized by the reaction of aldehydes and ketones carbonyls with acetone cyanohydrin in the presence of ionic liquid.

2. The method according to claim 1, characterized in that The aldehyde and ketone carbonyl compounds are phenylacetaldehyde, phenylpropionaldehyde, butyraldehyde, valeraldehyde, hexanal, 2-methylvaleraldehyde, isovaleraldehyde, 2-pentanone, 3-pentanone, 3-methylbutanone, pinacolone, 4-heptanone, 5-methylhexanone, 5-chloro-2-pentanone or cyclohexanone.

3. The method according to claim 1, characterized in that The ionic liquid is 1-butyl-3-methylimidazolium trifluoroacetate, 1-ethyl-3-methylimidazolium trifluoroacetate or 1-butyl-3-methylimidazolium dinitrile amine salt.

4. The method according to claim 1, characterized in that: The amount of acetone cyanohydrin used is 1.0-4.0 times the equivalent of the aldehyde or ketone carbonyl compound, and the amount of ionic liquid used is 2.0-4.0 times the equivalent of the aldehyde or ketone carbonyl compound.

5. The method according to claim 4, characterized in that The amount of acetone cyanohydrin used is 2.0-3.0 times the equivalent of the aldehyde and ketone carbonyl compounds, and the amount of ionic liquid used is 2.0-3.0 times the equivalent of the aldehyde and ketone carbonyl compounds.

6. The method according to claim 5, characterized in that The amount of acetone cyanohydrin used is 1.0 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 method according to claim 1, characterized in that: After the reaction is completed, the organic phase is washed with water, extracted and concentrated.

9. The α-hydroxynitrile prepared by the method according to any one of claims 1 to 8, wherein the general structural formula of the α-hydroxynitrile is: In the formula, R1 represents 1-Me-ph-, 1-Et-ph-, Me-, Et-, m-Bu-, i-Bu-, t-Bu-, m-pr-, i-pr- or 3-cl-m-pr-; R2 represents H-, Me-, Et- or m-pr-.

10. Use of the α-hydroxynitrile according to claim 9 as an intermediate in the chemical and pharmaceutical fields.

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