Calix [4] arene cyclohexanediamine derivative and method for green catalysis of asymmetric Aldol reaction by calix [4] arene cyclohexanediamine derivative

Abstract

The invention relates to the technical field of catalytic organic synthesis, in particular to calix [4] arene cyclohexanediamine derivatives and a method for green catalysis of asymmetric Aldol reaction by the calix [4] arene cyclohexanediamine derivatives. The method comprises the following steps: by taking aromatic aldehyde and cyclic ketone as raw materials, calix [4] arene cyclohexanediamine derivative as a phase transfer catalyst, p-nitrobenzoic acid as an additive and water as a solvent, reacting at 25 DEG C for 24-48 hours, adding dichloromethane after the reaction is finished, extracting and separating to obtain an organic phase, drying by using anhydrous Na2SO4, and separating and purifying by column chromatography to obtain an Aldol product. The calix [4] arene cyclohexanediamine derivative is mild in synthesis process condition and high in catalytic reaction efficiency, asymmetric Aldol reaction catalyzed by the calix [4] arene cyclohexanediamine derivative takes water as a solvent, the calix [4] arene cyclohexanediamine derivative is green and environment-friendly, good dr value and ee value can be obtained through catalytic reaction at room temperature, and the calix [4] arene cyclohexanediamine derivative has a wide application prospect.

Description

Technical Field

[0001] The invention relates to the technical field of catalytic organic synthesis, and in particular to a calix[4]arene cyclohexanediamine derivative and a method for green catalytic asymmetric Aldol reaction thereof. Background Art

[0002] In recent years, with the continuous understanding and in-depth study of the concept of chirality, controlling the optical selectivity and diastereoselectivity of Aldol reactions has become an important research topic. At present, asymmetric Aldol reactions catalyzed by small organic molecules and metal complexes have been widely reported in the literature, but the catalysts used in the reaction still have some disadvantages, such as being harmful to the environment, non-renewable, highly toxic, poorly stable, and requiring low temperature reactions.

[0003] Chiral cyclohexanediamine derivatives are often used in the study of catalytic asymmetric Aldol reactions. In 2023, Guo's team successfully designed and synthesized a (1R,2R)-1,2-cyclohexanediamine pendant helical polyphenylisocyanate-loaded catalyst 1, which can catalyze the organic asymmetric Aldol reaction of p-nitrobenzaldehyde and cyclohexanone with an enantioselectivity of 49% ee and a diastereoselectivity of 60:40dr. In 2021, Sato et al. designed and synthesized a bifunctional immobilized polymer catalyst 2 based on a proline amide combination, intended for use in Aldol reactions in a flow system. The two functions of the catalyst are located on different grafted polymers, and the interaction between the grafted polymers promotes the high conversion rate and high enantioselectivity of the asymmetric Aldol reaction.

[0004]

[0005] However, the synthesis of these catalysts is complicated, the preparation conditions are harsh, and the cost is high, making them difficult to use in industry. Therefore, the development of a new type of low-cost, easy-to-synthesize, and efficient green catalyst remains the core content of current research in this field. Summary of the invention

[0006] The present invention provides a calix[4]arene cyclohexanediamine derivative and a method for green catalysis of asymmetric Aldol reaction. The cavity structure of calixarene interacts with the phase transfer functional group, which can effectively control the substrate in a certain space, thereby achieving an efficient catalytic effect.

[0007] The technical solution adopted by the present invention to solve the technical problem is: a calix[4]arene cyclohexanediamine derivative, whose structural formula is:

[0008]

[0009] The method for green catalysis of asymmetric Aldol reaction using the derivative comprises the following steps:

[0010] (1) Using aromatic aldehyde and cyclic ketone as raw materials, calix[4]arene cyclohexanediamine derivative as phase transfer catalyst, p-nitrobenzoic acid as additive, and water as solvent to carry out Aldol catalytic reaction; the reaction temperature is 25° C., and the reaction time is 24 to 48 hours;

[0011] Among them, the aromatic aldehyde is benzaldehyde, substituted benzaldehyde, naphthaldehyde, pyridinealdehyde or thiophenealdehyde; among them, the substituted benzaldehyde is benzaldehyde in which the hydrogen on the benzene ring is substituted by 1 to 2 substituents, and the substituents are one or more of fluorine, chlorine, bromine, iodine, nitro, cyano, trifluoromethyl, and phenyl.

[0012] The cyclic ketone is cyclobutanone, cyclopentanone, cyclohexanone, cycloheptanone, pyrone or thiophenone.

[0013] The molar ratio of the aromatic aldehyde to the cyclic ketone is 1:1-2; the amount of the catalyst is 2 mol% of the aromatic aldehyde; the amount of p-nitrobenzoic acid is 2 mol% of the aromatic aldehyde; and the amount of water is 1-2 mL when 0.5 mmol of the aromatic aldehyde participates in the reaction.

[0014] (2) After the reaction in step (1) is completed, dichloromethane is added, the organic phase is extracted and separated, washed with saturated brine, and dried over anhydrous sodium sulfate; and separated by column chromatography to obtain the Aldol product.

[0015] The beneficial effects of the present invention are as follows: the method for green catalysis of asymmetric Aldol reaction of calix[4]arene cyclohexanediamine derivatives provided by the present invention, the chemical bonds modified on the upper edge of calixarene are amide bonds and primary amine bonds, so that the chiral environment can be established completely by relying on the catalytic center modified on the upper edge. The calixarene derivatives have hydrophobic groups and hydrophilic groups on the skeleton structure, which can effectively connect the aqueous phase and the organic phase during the catalytic reaction, thereby exerting the function of phase transfer catalysis, and have high selectivity for cyclic ketones of different sizes. The synthesis process conditions of calix[4]arene cyclohexanediamine derivatives are mild, high synthesis yield, high catalytic efficiency, good stereoselectivity, etc. The present invention will provide a new way to expand the ideas of chiral modification of calixarene and enrich the chemical methods of chiral modification of the upper edge of calixarene. DETAILED DESCRIPTION

[0016] The present invention will be further described below in conjunction with specific examples. It should be understood that the examples are only used to illustrate the present invention but not to limit the scope of the present invention.

[0017] Example 1

[0018] 1. Synthesis of Calix[4]cyclohexanediamine Catalyst I

[0019]

[0020] 5-formyl-25,26,27,28-tetrapropoxycalix[4]arene (620 mg, 1 mmol), cyclohexanediamine acetyl (314 mg, 2 mmol), and 100 mg of anhydrous sodium sulfate were weighed in a round-bottom flask, and methanol was used as a solvent (20 mL). The reaction was refluxed and monitored by TLC until the reaction of the raw materials was complete. Sodium borohydride (189 mg, 5 mmol) was added in two batches under ice-water bath conditions. The reaction temperature was raised to 60°C. The reaction was monitored by TLC until the reaction of the raw materials was complete. The reaction was quenched, the reaction solution was concentrated, and then extracted with water and dichloromethane. The organic phases were collected and combined, concentrated, and recrystallized with dichloromethane / acetonitrile to obtain a pure calixarene imine intermediate compound (525 mg, yield 69%).

[0021] White solid; Mp: 1 H NMR (300MHz, CDCl3) δ6.58–6.38(m,11H),5.43(d,J=7.0Hz,1H),4.37(d,J=13.3Hz,4H),3.76(t,J=7.5Hz,8H),3.53–3.35(m,2H),3.26(d,J=12.8Hz ,1H),3.12–2.99(m,4H),2.19–2.05(m,1H),1.99(d,J=9.4Hz,1H),1.92–1 .77(m,12H),1.72–1.54(m,1H),1.30–1.02(m,4H),0.91(t,J=7.4Hz,12H). 13 CNMR(75MHz,CDCl3)δ170.30,156.78,156.65,156.58,155.75,135.34,1 35.30,135.28,135.16,135.10,135.04,135.03,133.88,128.19,128.15 ,128.13,128.07,127.97,127.90,121.98,121.90,121.65,76.77,59.82 ,53.42,49.98,32.63,31.82,31.07,24.93,24.77,23.80,23.31,10.42.

[0022]

[0023] The calixarene imine intermediate compound (761 mg, 1 mmol) and potassium carbonate (1.1 g, 8 mmol) were weighed in a round-bottom flask in sequence, and dichloromethane was used as solvent (40 mL). The mixture was stirred at 0°C for 1 h, and benzyl bromide (1.92 mL, 8 mmol) was added. The mixture was stirred at room temperature, and the reaction progress was monitored by TLC. After 6 h, the raw materials reacted completely, and the reaction solution was concentrated. The mixture was recrystallized from dichloromethane / acetonitrile to obtain a pure acetyl-protected cyclohexanediamine calixarene intermediate. The intermediate was then added to a round-bottom flask, and CH3OH was used as solvent (30 mL). 36% HCl (1.5 mL) was added dropwise in three batches. The mixture was refluxed for 24 h, and the reaction was stopped. The mixture was extracted with water and dichloromethane three times. The concentrated organic phases were combined and recrystallized from dichloromethane / acetonitrile to obtain compound I (495 mg, yield 68%).

[0024] White solid; Mp: 81℃; 1 H NMR (300MHz, CDCl3) δ7.40–7.12(m,5H),6.71–6.40(m,10H),6.29(t,J=7.5Hz,1H),4.43(d,J=13.2Hz,4H),3.91–3.73(m,8H),3.55(dd,J =30.1,13.5Hz,2H),3.29–2.93(m,6H),2.67–2.48(m,1H),2.17–2.02(m,1H),2.02–1.83(m,10H),1.79–1.55(m,4H),1.14–0.90(m,16H). 13 C NMR (75MHz, CDCl3) δ156.69,156.65,156.59,155.53,140.48,135.32,135.28,135.07 ,135.01,134.77,134.75,133.23,129.08,128.61,128.29,128.23,128.18,128.13,12 6.76,122.01,121.78,76.88,76.83,76.80,64.61,53.91,52.99,51.38,35.18,31.17,31.09,31.06,25.93,25.35,23.40,23.35,23.30,22.67,10.50,10.46,10.43,10.41.

[0025] 2. Synthesis of Calix[4]cyclohexanediamine Catalyst II

[0026]

[0027] The intermediate compound of calixarene imine (761 mg, 1 mmol) and potassium carbonate (1.1 g, 8 mmol) were weighed in a 100 mL round-bottom flask, acetonitrile was used as solvent (40 mL), stirred at room temperature for 1 h, iodoethane (0.64 mL, 8 mmol) was added, refluxed for 12 h, the reaction was stopped, extracted with dichloromethane and water three times, the organic phase was concentrated, and the pure acetyl-protected cyclohexanediamine calixarene intermediate was recrystallized from dichloromethane / acetonitrile. The intermediate was then added to a 50 mL round-bottom flask, CH3OH was used as solvent (30 mL), 36% HCl (1.5 mL) was added dropwise in three batches, refluxed for 24 h, the reaction was stopped, extracted with dichloromethane and water three times, the organic phase was concentrated, and the compound II (526 mg, yield 88%) was obtained.

[0028] Yellow solid; Mp: 57℃; 1 H NMR (300MHz, CDCl3) δ6.67–6.52(m,11H),4.50–4.38(m,4H),3.89–3.78(m,8H),3.51(d,J=14.0Hz,1H),3.18–3.09(m,4H),3.03(d,J=14.1Hz, 1H),2.58–2.49(m,1H),2.38–2.21(m,2H),2.18–2.11(m,1H),1.99–1.8 7(m,9H),1.83–1.60(m,5H),1.22–0.96(m,16H),0.91(t,J=7.0Hz,3H). 13 C NMR (75MHz, CDCl3) δ156.73,156.58,156.54,155.38,135.30,135.25,135.22,135. 15,135.09,134.98,134.77,134.71,133.96,128.26,128.17,128.09,127.79,122.0 3,121.95,121.75,77.36,76.88,76.83,76.80,76.77,65.17,52.96,51.30,43.52,35.25,31.12,31.05,26.12,25.27,23.39,23.33,23.06,14.54,10.47,10.44,10.42.

[0029] 3. Synthesis of Calix[4]cyclohexanediamine Catalyst III

[0030]

[0031] Weigh the calixarene imine intermediate compound (761 mg, 1 mmol) and potassium carbonate (1.1 g, 8 mmol) in a 100 mL round-bottom flask, use acetonitrile as solvent (40 mL), stir at room temperature for 1 h, add iodohexane (1.1 mL, 8 mmol), reflux for 12 h, stop the reaction, extract with dichloromethane and water three times, concentrate the organic phase, and recrystallize with dichloromethane / acetonitrile to obtain pure acetyl-protected cyclohexanediamine calixarene intermediate. Then add the intermediate to a 50 mL round-bottom flask, use CH3OH as solvent (30 mL), add 36% HCl (1.5 mL) dropwise in three batches, reflux for 24 h, stop the reaction, extract with dichloromethane and water three times, concentrate the organic phase, and recrystallize with dichloromethane / acetonitrile to obtain compound III (337 mg, yield 60%).

[0032] Yellow solid; Mp: 49℃; 1 H NMR (300MHz, CDCl3) δ6.82–6.56(m,5H),6.47(s,6H),4.44(dd,J=13.4,5.7Hz,4H),3.94–3.74(m,8H),3.52(d,J=13.7Hz,1H),3.22–3.01(m,5H ),2.62–2.48(m,1H),2.49–2.33(m,1H),2.35–2.21(m,1H),2.13(t,J=9 .4Hz,1H),2.04–1.67(m,13H),1.42–1.10(m,12H),1.07–0.83(m,16H). 13 C NMR (75MHz, CDCl3) δ157.06,156.32,156.30,155.72,135.76,135.72,135.20,135.16,134.8 9,134.83,134.79,134.77,133.89,128.82,128.41,128.33,127.99,127.94,121.99,121.75 ,77.36,76.86,76.83,76.78,65.52,53.60,51.34,49.81,34.90,32.00,31.11,31.06,29.13,27.30,26.04,25.26,23.43,23.40,23.33,23.28,22.89,22.85,14.29,10.57,10.38,10.32.

[0033] 4. Synthesis of Calix[4]cyclohexanediamine Catalyst IV

[0034]

[0035] Weigh the calixarene imine intermediate compound (761 mg, 1 mmol) and potassium carbonate (1.1 g, 8 mmol) in a 100 mL round-bottom flask, use acetonitrile as solvent (40 mL), stir at room temperature for 1 h, add 2-iodopropane (0.8 mL, 8 mmol), reflux for 12 h, stop the reaction, extract with dichloromethane and water three times, concentrate the organic phase, and recrystallize with dichloromethane / acetonitrile to obtain pure acetyl-protected cyclohexanediamine calixarene intermediate. Then add the intermediate to a 50 mL round-bottom flask, use CH3OH as solvent (30 mL), add 36% HCl (1.5 mL) dropwise in three batches, reflux for 24 h, stop the reaction, extract with dichloromethane and water three times, concentrate the organic phase, and recrystallize with dichloromethane / acetonitrile to obtain compound IV (416 mg, yield 78%).

[0036] Yellow solid; Mp: 71℃; 1 H NMR (300MHz, CDCl3) δ6.72–6.47(m,11H),4.44(dd,J=13.3,5.8Hz,4H),3.83(t,J=7.5Hz,8H),3.48(d,J=14.2Hz,1H) ,3.31–3.02(m,5H),2.94–2.73(m,1H),2.52–2.34(m,1H),2.23–2.05(m,1H),2.00–1.55(m,14H),1.35–0.88(m,22H). 13 C NMR (75MHz, CDCl3) δ156.77,156.54,156.50,155.32,135.35,135.33,135.22,135.18, 135.10,135.04,134.85,134.72,134.57,128.18,128.15,128.13,128.10,128.06,128 .04,127.84,122.00,121.93,121.65,76.81,76.79,62.64,51.83,48.64,48.02,35.08,31.09,31.03,28.19,26.38,25.37,23.37,23.34,23.31,22.96,18.60,10.45,10.39.

[0037] Example 2

[0038] The catalytic effects of calix[4]cyclohexanediamine derivatives I to IV were screened. The experimental method is: p-nitrobenzaldehyde (0.5mmol), cyclohexanone (0.5mmol), calixarene catalyst (2mol%), p-nitrobenzoic acid (2mol%) and water (1.5mL) were added to the test tube in sequence, and the reaction was stirred at 25°C for 24h before the reaction was completed. After the reaction was completed, the reaction solution was concentrated and separated by chromatography column (ethyl acetate: petroleum ether = 1:5) to obtain the Aldol addition product.

[0039] 1. Using calixarene catalyst I, the yield of the target product is 88%, the anti / syn ratio is 59:41, and the ee of the anti product is 88%;

[0040] 2. Using calixarene catalyst II, the yield of the target product is 94%, the anti / syn ratio is 87:13, and the ee of the anti product is 94%;

[0041] 2. Using calixarene catalyst III, the yield of the target product is 90%, the anti / syn ratio is 80:20, and the ee of the anti product is 90%;

[0042] 2. Using calixarene catalyst IV, the yield of the target product is 91%, the anti / syn is 64:36, and the ee of the anti product is 91%.

[0043] Example 3

[0044] The amount of solvent used in the reaction was screened. The experimental method was as follows: p-nitrobenzaldehyde (0.5 mmol), cyclohexanone (0.5 mmol), calixarene catalyst II (2 mol%), p-nitrobenzoic acid (2 mol%) and water were added to a test tube in sequence, and the reaction was stirred at 25°C for 24 hours before the reaction ended. After the reaction, the reaction solution was concentrated and separated by chromatography (ethyl acetate: petroleum ether = 1:5) to obtain the Aldol addition product.

[0045] 1. The amount of water used was 0.5 mL, the yield of the target product was 68%, the anti / syn ratio was 86:14, and the ee of the anti product was 93%;

[0046] 2. The amount of water used was 1 mL, the yield of the target product was 92%, the anti / syn ratio was 87:13, and the ee of the anti product was 93%;

[0047] 3. The amount of water used was 1.5 mL, the yield of the target product was ≥ 99%, the anti / syn ratio was 87:13, and the ee of the anti product was 94%;

[0048] 4. The amount of water used is 2 mL, the yield of the target product is ≥99%, the anti / syn is 63:37, and the ee of the anti product is 94%.

[0049] Example 4

[0050] The optimal experimental conditions in Example 3 were used to investigate the applicable scope of the aldehyde substrate for catalytic asymmetric reaction. The experimental method is: p-nitrobenzaldehyde (0.5mmol), cyclohexanone (0.5mmol), calixarene catalyst II (2mol%), p-nitrobenzoic acid (2mol%) and water (1.5mL) were added to a test tube in sequence, and the reaction was stirred at 25°C for 24h before the reaction was completed. After the reaction was completed, the reaction solution was concentrated and separated by chromatography column (ethyl acetate: petroleum ether = 1:5) to obtain a pure Aldol addition product with a yield of ≥99%, anti / syn of 87:13, and anti product ee of 94%.

[0051] Example 5

[0052] This example is the same as Example 4, except that o-nitrobenzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 87%, an anti / syn ratio of 71:29, and an ee of the anti product of 93%.

[0053] Example 6

[0054] This example is the same as Example 4, except that m-nitrobenzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 92%, an anti / syn ratio of 75:25, and an ee of the anti product of 87%.

[0055] Example 7

[0056] This example is the same as Example 4, except that m-2,4-dinitrobenzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 91%, an anti / syn ratio of 86:14, and an ee of the anti product of 91%.

[0057] Example 8

[0058] This example is the same as Example 4, except that p-cyanobenzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 93%, an anti / syn ratio of 74:26, and an ee of the anti product of 93%.

[0059] Example 9

[0060] This example is the same as Example 4, except that p-trifluoromethylbenzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 93%, an anti / syn ratio of 87:13, and an ee of the anti product of 93%.

[0061] Example 10

[0062] This example is the same as Example 4, except that 2-fluorobenzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 77%, an anti / syn ratio of 99:1, and an ee of the anti product of 93%.

[0063] Embodiment 11

[0064] This example is the same as Example 4, except that 4-fluorobenzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 72%, an anti / syn ratio of 75:25, and an ee of the anti product of 93%.

[0065] Example 12

[0066] This example is the same as Example 4, except that 4-chlorobenzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 70%, an anti / syn ratio of 61:39, and an ee of the anti product of 88%.

[0067] Embodiment 13

[0068] This example is the same as Example 4, except that 3-chlorobenzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 80%, an anti / syn ratio of 70:30, and an ee of the anti product of 89%.

[0069] Embodiment 14

[0070] This example is the same as Example 4, except that 4-bromobenzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 77%, an anti / syn ratio of 64:36, and an ee of the anti product of 88%.

[0071] Embodiment 15

[0072] This example is the same as Example 4, except that 2-iodobenzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 83%, an anti / syn ratio of 71:29, and an anti product ee of 95%.

[0073] Example 16

[0074] This example is the same as Example 4, except that benzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 72%, an anti / syn ratio of 65:35, and an ee of the anti product of 84%.

[0075] Embodiment 17

[0076] This example is the same as Example 4, except that 1-naphthylbenzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 63%, an anti / syn ratio of 57:43, and an ee of the anti product of 86%.

[0077] Embodiment 18

[0078] This example is the same as Example 4, except that 2-naphthobenzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 85%, an anti / syn ratio of 76:24, and an ee of the anti product of 89%.

[0079] Embodiment 19

[0080] This example is the same as Example 4, except that p-phenylbenzaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 75%, an anti / syn ratio of 67:33, and an ee of the anti product of 96%.

[0081] Embodiment 20

[0082] This example is the same as Example 4, except that p-2-pyridinecarboxaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 84%, an anti / syn ratio of 68:32, and an ee of the anti product of 89%.

[0083] Embodiment 21

[0084] This example is the same as Example 4, except that p-5-phenyl-2-thiophenecarboxaldehyde is used instead of p-nitrobenzaldehyde to obtain the Aldol addition product with a yield of 55%, an anti / syn ratio of 64:36, and an ee of the anti product of 83%.

[0085] Embodiment 22

[0086] This example refers to Example 4, and uses cyclobutanone instead of cyclohexanone to obtain a pure Aldol addition product with a yield of >50%, an anti / syn ratio of 37:63, and an anti product ee of 34%.

[0087] Embodiment 23

[0088] This example is the same as Example 4, except that cyclopentanone is used instead of cyclohexanone to obtain the Aldol addition product with a yield of 75%, an anti / syn ratio of 56:44, and an anti product ee of 92%.

[0089] Embodiment 24

[0090] This example is the same as Example 4, except that cycloheptanone is used instead of cyclohexanone to obtain the Aldol addition product with a yield of 66%, an anti / syn ratio of 46:54, and an ee of the anti product of 64%.

[0091] Embodiment 25

[0092] This example is the same as Example 4, except that tetrahydrothiopyranone is used instead of cyclohexanone to obtain the Aldol addition product with a yield of 63%, an anti / syn ratio of 59:41, and an ee of the anti product of 80%.

[0093] Embodiment 26

[0094] This example is the same as Example 4, except that tetrahydropyrone is used instead of cyclohexanone to obtain the Aldol addition product with a yield of 60%, an anti / syn ratio of 44:56, and an ee of the anti product of 81%.

[0095] Comparative Example 1

[0096] This comparative example is the same as Example 4, except that acetic acid is used instead of p-nitrobenzoic acid as an additive to obtain an Aldol addition product with a yield of 26%, an anti / syn ratio of 80:20, and an ee of the anti product of 92%.

[0097] Comparative Example 2

[0098] This comparative example is the same as Example 4, except that trifluoroacetic acid is used instead of p-nitrobenzoic acid as an additive to obtain an Aldol addition product with a yield of 61%, an anti / syn ratio of 81:19, and an ee of the anti product of 91%.

[0099] Comparative Example 3

[0100] This comparative example is the same as Example 4, except that an excess of cyclohexanone itself was used as a solvent to obtain an Aldol addition product with a yield of 50%, an anti / syn ratio of 41:59, and an anti product ee of 45%.

[0101] Based on the above ideal embodiments of the present invention, the relevant staff can make various changes and modifications without departing from the technical concept of the present invention through the above description. The technical scope of the present invention is not limited to the contents of the specification, and its technical scope must be determined according to the scope of the claims.

Claims

1. A calix[4]arene cyclohexanediamine derivative, characterized in that: The structure of the calix[4]arene cyclohexanediamine derivative is shown in the following formula:

2. A use of the calix[4]arene cyclohexanediamine derivative as claimed in claim 1, characterized in that: The calix[4]arene cyclohexanediamine derivatives are used for green catalysis of asymmetric aldol reactions of aromatic aldehydes and cyclic ketones.

3. The use of the calix[4]arene cyclohexanediamine derivative according to claim 2, characterized in that: The method steps of the green catalytic asymmetric Aldol reaction of aromatic aldehydes and cyclic ketones are as follows: (1) Using aromatic aldehyde and cyclic ketone as raw materials, calix[4]arene cyclohexanediamine derivative as phase transfer catalyst, p-nitrobenzoic acid as additive, water as solvent, and reacting at 25°C for 24-48 hours; (2) After the reaction in step (1) is completed, dichloromethane is added, the organic phase is extracted and separated, washed with saturated brine, and dried over anhydrous sodium sulfate; and separated by column chromatography to obtain the Aldol product.

4. The use of the calix[4]arene cyclohexanediamine derivative according to claim 3, characterized in that: The aromatic aldehyde in step (1) is benzaldehyde, substituted benzaldehyde, naphthaldehyde, pyridinealdehyde or thiophenealdehyde; wherein the substituted benzaldehyde is a benzaldehyde in which the hydrogen on the benzene ring is substituted by 1 to 2 substituents, and the substituents are one or more of fluorine, chlorine, bromine, iodine, nitro, cyano, trifluoromethyl and phenyl.

5. The use of the calix[4]arene cyclohexanediamine derivative according to claim 3, characterized in that: The cyclic ketone in step (1) is cyclobutanone, cyclopentanone, cyclohexanone, cycloheptanone, pyrone or thiopyranone.

6. The use of the calix[4]arene cyclohexanediamine derivative according to claim 3, characterized in that: The molar ratio of the aromatic aldehyde to the cyclic ketone in step (1) is 1:1-2; the amount of the catalyst is 2 mol% of the aromatic aldehyde; the amount of p-nitrobenzoic acid is 2 mol% of the aromatic aldehyde; and the amount of water used when 0.5 mmol of the aromatic aldehyde participates in the reaction is 1-2 mL.

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