Column [n] arene benzoquinone oxime ortho-position functionalized derivative and preparation method thereof

Abstract

The invention discloses a column [n] arene benzoquinone oxime ortho-position functionalized derivative and a preparation method thereof, and particularly relates to a preparation method for obtaining the column [n] arene benzoquinone oxime ortho-position functionalized derivative by reacting column [n] arene [1] benzoquinone oxime with a Grignard reagent. In the structure of column [n] arene [1] benzoquinone oxime, when alpha, beta-unsaturated ketone and a Grignard reagent are subjected to nucleophilic addition reaction, a 1, 4-addition product with high yield can be obtained, and no 1, 2-addition product exists. The method is mainly characterized in that protons can be removed from hydroxyl of oxime in column [n] arene [1] benzoquinone oxime under an alkaline condition, and oxygen negative ions of the hydroxyl are combined with positively charged metal magnesium atoms in a Grignard reagent to form a six-membered ring transition state, so that R negative ions can attack a No.4 carbon atom of alpha, beta-unsaturated ketone, and a 1, 4-addition reaction is carried out. The preparation method disclosed by the invention is mild in condition and can be carried out without harsh reaction conditions.

Description

Technical Field

[0001] The present invention belongs to the technical field of chemical synthesis preparation, and relates to an ortho-functionalized derivative of pillar[n]arene benzoquinone oxime and a preparation method thereof. Background Art

[0002] Macrocyclic arenes are important tools for supramolecular chemistry research. Since Pedersen reported crown ethers in 1967, the synthesis of macrocyclic host compounds has gradually attracted extensive attention and interest from chemists. The early studies on crown ethers, cryptands, and spherands revealed the basic concepts of supramolecular chemistry and laid the foundation for supramolecular chemistry. For their outstanding contributions in this regard, Pedersen, Cram, and Lehn were awarded the Nobel Prize in Chemistry in 1987. These macrocyclic structures have been widely applied in many fields such as molecular recognition, self-assembly, molecular machines and devices, gas adsorption, drug solubilization and targeted delivery, supramolecular catalysis, chemical sensing, supramolecular polymers, etc.

[0003] In 2008, Professor Ogoshi of Kanazawa University in Japan reported pillar[n]arenes (n = 5, 6), which are macrocyclic arenes bridged by methylene groups formed by 1,4-dimethoxybenzene and paraformaldehyde under the catalysis of Lewis acid. The raw materials of this macrocyclic molecule are easily available, synthesized in one pot and in large quantities, with a relatively high yield and excellent host-guest properties, showing broad application prospects in the field of supramolecular chemistry. Since its report, its unique structure and excellent properties have attracted extensive attention from supramolecular chemists, and are mainly applied in gas adsorption, ion channels, supramolecular amphiphilic assembly, drug delivery, and supramolecular polymers, etc. Currently, the functionalization modification methods of pillar[n]arenes mainly focus on the alkoxy substituents of the repeating unit benzene ring. The alkyl groups can be removed by boron tribromide, and then mono-functional or multi-functional pillar[n]arene derivatives can be carried out, or oxidation reactions can be performed (Chem. Rev. 2016, 116, 7937).

[0004] In 2019, the research group of Professor Wen Ke used pillar[5]arene for an oxidation reaction to obtain pillar[4]arene[1]benzoquinone, which was then reacted under the condition of hydroxylamine hydrochloride to obtain the product of pillar[4]arene[1]benzoquinone oxime (Org. Biomol. Chem. 2019, 17, 4975). Generally, the addition reaction of α,β-unsaturated ketone with Grignard reagent gives mainly the typical 1,2-addition product, and it is very difficult to obtain the 1,4-addition product. Only under extremely few harsh conditions can the 1,4-addition be achieved. However, in the structure of pillar[4]arene[1]benzoquinone oxime, there is also the structure of α,β-unsaturated ketone. When reacting with Grignard reagent, the obtained product is the 1,4-addition product without the 1,2-addition product; this is an important discovery for the reaction of Grignard reagent with α,β-unsaturated ketone and has great scientific significance. In addition, due to the stability of the pillar[n]arene structure, ortho-functionalization is also a great challenge. Summary of the Invention

[0005] To overcome the problem of the selectivity of the nucleophilic addition reaction of Grignard reagent with α,β-unsaturated ketone existing in the prior art, the object of the present invention is to provide an ortho-functionalized derivative of pillar[n]arene benzoquinone oxime and a preparation method thereof. This method first oxidizes and then undergoes nucleophilic addition, which can achieve ortho-functionalized pillararene without destroying the cyclic structure of the macrocycle, and this macrocycle structure and pillararene will produce significant functional differences.

[0006] To achieve the above object, the present invention adopts the following technical solutions to be realized:

[0007] An ortho-functionalized derivative of pillar[n]arene benzoquinone oxime has the following general structural formula:

[0008]

[0009] Among them, n is 4 or 5.

[0010] A preparation method of an ortho-functionalized derivative of pillar[n]arene benzoquinone oxime, which reacts pillar[n]arene[1]benzoquinone oxime with Grignard reagent to obtain the preparation method of the ortho-functionalized derivative of pillar[n]arene benzoquinone oxime.

[0011] Furthermore, the reaction site of pillar[n]arene[1]benzoquinone oxime and Grignard reagent occurs at the ortho-position of pillar[n]arene[1]benzoquinone oxime.

[0012] Furthermore, the specific process is as follows:

[0013] Under nitrogen protection, to the solution of pillar[n]arene[1]benzoquinone oxime, add the Grignard reagent solution, react at low temperature until the color of the reaction solution changes from yellow to red, and then perform post-treatment to obtain the ortho-functionalized derivative of pillar[n]arene benzoquinone oxime.

[0014] Furthermore, the molar ratio of pillar[n]arene[1]benzoquinone oxime to the Grignard reagent is 0.4 mmol: 1.5 - 3.0 mmol.

[0015] Furthermore, the chemical formula of the Grignard reagent is RMgBr, and the R group is methyl, ethyl, propyl, butyl, n-pentyl, n-hexyl, isopropyl, cyclopropyl, cyclopentyl, cyclohexyl, thiophene, furan, substituted olefin, p-methoxyphenyl, 4-fluorophenyl, phenyl, naphthyl or biphenyl.

[0016] Furthermore, the reaction temperature is -78 °C.

[0017] Furthermore, the reaction time is 30 - 60 minutes.

[0018] Furthermore, the specific process of post-treatment is as follows: Pour the reaction solution into saturated ammonium chloride solution, separate the organic phase, dry it with anhydrous sodium sulfate, then concentrate it under reduced pressure, separate it by column chromatography, elute with organic solvent, and obtain the ortho-functionalized derivative of pillar[n]arene benzoquinone oxime.

[0019] Furthermore, the solvent in the solution of pillar[n]arene[1]benzoquinone oxime is tetrahydrofuran.

[0020] Furthermore, the organic solvent is a mixture of ethyl acetate and dichloromethane, and the volume ratio of ethyl acetate to dichloromethane is 1:99, 5:95, 40:60, or the organic solvent is a mixture of ethyl acetate and n-hexane, and the volume ratio of ethyl acetate to n-hexane is 50:50, 40:60.

[0021] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0022] In the structure of pillar[n]arene[1]benzoquinone oxime, when α,β-unsaturated ketone undergoes a nucleophilic addition reaction with the Grignard reagent, a high-yield 1,4-addition product can be obtained, and there is no 1,2-addition product. This is mainly because the hydroxyl group of the oxime in pillar[n]arene[1]benzoquinone oxime can deprotonate under alkaline conditions, and the oxygen anion of the hydroxyl group combines with the positively charged magnesium atom in the Grignard reagent to form a six-membered ring transition state, which is beneficial for the R anion to attack the 4-position carbon atom of α,β-unsaturated ketone, resulting in a 1,4-addition reaction. This structure of pillar[n]arene[1]benzoquinone oxime can provide a very simple preparation method for the ortho-functionalization of pillararenes. This preparation method has mild conditions and can be carried out without harsh reaction conditions. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 It is a schematic diagram of the preparation method of pillararene derivatives;

[0024] Figure 2 It is the hydrogen spectrum of compound 1a;

[0025] Figure 3 It is the carbon spectrum of Compound 1a;

[0026] Figure 4 It is the hydrogen spectrum of Compound 1b;

[0027] Figure 5 It is the carbon spectrum of Compound 1b;

[0028] Figure 6 It is the hydrogen spectrum of Compound 1c;

[0029] Figure 7 It is the carbon spectrum of Compound 1c;

[0030] Figure 8 It is the hydrogen spectrum of Compound 1d;

[0031] Figure 9 It is the carbon spectrum of Compound 1d;

[0032] Figure 10 It is the hydrogen spectrum of Compound 1e;

[0033] Figure 11 It is the carbon spectrum of Compound 1e;

[0034] Figure 12 It is the hydrogen spectrum of Compound 1f;

[0035] Figure 13 It is the carbon spectrum of Compound 1f;

[0036] Figure 14 It is the hydrogen spectrum of Compound 1g;

[0037] Figure 15 It is the carbon spectrum of Compound 1g;

[0038] Figure 16 It is the hydrogen spectrum of Compound 1h;

[0039] Figure 17 It is the carbon spectrum of Compound 1h;

[0040] Figure 18 It is the hydrogen spectrum of Compound 1i;

[0041] Figure 19 It is the carbon spectrum of Compound 1i;

[0042] Figure 20 It is the hydrogen spectrum of Compound 1j;

[0043] Figure 21 It is the carbon spectrum of Compound 1j;

[0044] Figure 22 It is the hydrogen spectrum of Compound 1k;

[0045] Figure 23 It is the carbon spectrum of Compound 1k;

[0046] Figure 24 It is the hydrogen spectrum of Compound 1l;

[0047] Figure 25 It is the carbon spectrum of Compound 1l;

[0048] Figure 26 It is the hydrogen spectrum of Compound 1m;

[0049] Figure 27 It is the carbon spectrum of Compound 1m;

[0050] Figure 28 It is the hydrogen spectrum of Compound 1n;

[0051] Figure 29 It is the carbon spectrum of Compound 1n;

[0052] Figure 30 It is the hydrogen spectrum of Compound 1o;

[0053] Figure 31 It is the carbon spectrum of Compound 1o;

[0054] Figure 32 It is the hydrogen spectrum of Compound 1p;

[0055] Figure 33 It is the carbon spectrum of Compound 1p. Detailed implementation manners

[0056] The present invention will be further described in detail below with reference to the accompanying drawings and embodiments:

[0057] The pillar[n]arene benzoquinone oxime ortho-functionalized derivative in the present invention is a pillar[5]arene derivative or a pillar[6]arene derivative.

[0058] Among them, the structural general formula of the pillar[n]arene benzoquinone oxime ortho-functionalized derivative is as follows:

[0059]

[0060] Among them, n is 4 or 5.

[0061] When n is 4, it is a pillar[5]arene derivative, and when n is 5, it is a pillar[6]arene derivative.

[0062] The present invention can refer to Figure 1 in the synthetic route, Figure 1 in which, when R is different groups, the corresponding prepared compounds are marked.

[0063] The o-functionalized derivatives of pillar[n]arene benzoquinone oxime are prepared by reacting pillar[n]arene[1]benzoquinone oxime with Grignard reagent.

[0064] Among them, the reaction site of pillar[n]arene[1]benzoquinone oxime and Grignard reagent occurs at the ortho position of pillar[n]arene[1]benzoquinone oxime.

[0065] The product obtained by reacting pillar[n]arene[1]benzoquinone oxime with Grignard reagent is the one that opens one carbon-carbon double bond of benzoquinone oxime.

[0066] The chemical formula of the Grignard reagent is RMgBr, and the R group can be methyl, ethyl, propyl, butyl, n-pentyl, n-hexyl, isopropyl, cyclopropyl, cyclopentyl, cyclohexyl, thiophene, furan, substituted alkene, p-methoxyphenyl, 4-fluorophenyl, phenyl, naphthyl or biphenyl, etc.

[0067] The preparation method of the o-functionalized derivatives of pillar[n]arene benzoquinone oxime includes the following steps:

[0068] The reactions are all carried out under nitrogen protection. Dissolve pillar[n]arene[1]benzoquinone oxime in tetrahydrofuran, and then slowly add the Grignard reagent solution at low temperature. React at low temperature for 30 minutes, and the color of the reaction solution changes from yellow to red. Then pour the reaction solution into saturated ammonium chloride solution, separate the organic phase, extract the aqueous phase with dichloromethane three times, combine the organic phases, dry with anhydrous sodium sulfate, and then concentrate under reduced pressure. Separate by column chromatography and elute with organic solvent to obtain the o-functionalized derivatives of pillar[n]arene benzoquinone oxime (compounds 1a-1p).

[0069] Among them, the tetrahydrofuran is an anhydrous solvent.

[0070] The solvent in the Grignard reagent solution is tetrahydrofuran, and the concentration of the Grignard reagent solution is 0.5 - 2.0 mol / L.

[0071] The low temperature is -78 °C, and the reaction time is 30 - 60 minutes.

[0072] The organic solvent is a mixture of ethyl acetate and dichloromethane, and the volume ratio of ethyl acetate to dichloromethane is 1:99, 5:95 or 40:60, or the organic solvent is a mixture of ethyl acetate and n-hexane, and the volume ratio of ethyl acetate to n-hexane is 50:50 or 40:60.

[0073] The molar ratio of pillar[n]arene[1]benzoquinone oxime to the Grignard reagent in the Grignard reagent solution is 0.4 mmol:1.5 - 3.0 mmol.

[0074] Example 1

[0075] In a 250 mL three-necked flask equipped with a nitrogen protection atmosphere, 0.4 mmol of pillar[n]arene[1]benzoquinone oxime was added, and then 40 mL of anhydrous tetrahydrofuran was added and stirred until dissolved. The three-necked flask was transferred to a low-temperature condition, stirred and cooled for a few minutes, the temperature was lowered to -78 °C, and then 2.5 mmol of Grignard reagent was slowly added to the three-necked flask. The color of the reaction solution gradually changed from yellow to red. After reacting at low temperature for 30 minutes, the reaction solution was poured into 30 mL of saturated ammonium chloride solution, the organic phase was separated, the aqueous phase was extracted three times with 30 mL of dichloromethane, and then the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. After column chromatography separation, the pillar[n]arene benzoquinone oxime ortho-functionalized derivative, namely compound 1a, was eluted with an organic solvent (i.e., eluent).

[0076] Among them, R is

[0077] Compound 1a: Separated by column chromatography, the eluent was ethyl acetate / dichloromethane (1:99), and a pale yellow solid was obtained with a yield of 74%. 1 H NMR (500 MHz, CDCl 3 , 298 K) δ 8.06 (s, OH), 7.11 (d, J = 2.0, 1H), 7.09 (s, 1H), 7.07–7.01 (m, 3H), 6.90 (d, J = 7.0 Hz, 2H), 6.85 (d, J = 3.5 Hz, 2H), 6.83 (s, 1H), 6.72 (d, J = 5.5 Hz, 2H), 6.62 (s, 1H), 6.25 (s, 1H), 4.94 (d, J = 6.5 Hz, 1H), 3.84–3.79 (m, 6H), 3.76–3.72 (m, 16H), 3.70 (s, 3H), 3.68–3.65 (m, 7H), 2.83 (ddd, J = 13.5 6.5, 2.5 Hz, 1H), 2.65 (dd, J = 13.5, 7.0 Hz, 1H), 2.53 (dd, J = 13.5, 2.5 Hz, 1H). 13 C NMR (126 MHz, CDCl 3, 298 K) δ 200.3, 157.6, 151.0, 150.9, 150.8, 150.7, 150.7, 150.6, 150.4, 150.2, 137.5, 131.8, 129.1, 128.9, 128.7, 128.7, 128.5, 128.1, 128.1, 127.8, 127.8, 127.1, 125.0, 114.8, 114.3, 114.1, 114.0, 113.9, 113.8, 113.6, 112.8, 60.5, 56.0, 56.0, 55.9, 55.8, 55.8, 55.5, 53.0, 51.9, 45.1, 31.6, 30.1, 29.5, 29.0, 28.8, 26.0, 22.7, 21.1, 14.2. HRMS(ESI) of 1a: calcd for C 49 H 51 NO 10 + [M + Na] + =836.3393, found m / z=836.3406.

[0078] Example 2

[0079] Same as Example 1, except that R is

[0080] Compound 1b: Separated by column chromatography, eluent was ethyl acetate / dichloromethane (1:99), obtained as a pale yellow solid, yield 52%. 1 H NMR(500 MHz, CDCl 3 , 298 K) δ 8.25 (s, OH), 7.77–7.75 (dd, J = 9.5, 2.5 2H), 7.66 (d, J = 1.5, 1H), 7.63 (d, J = 8.5 Hz, 1H), 7.44–7.42 (s, J = 10.5, 6.5, 4.5 Hz, 2H), 7.28 (d, J = 8.0 Hz, 1H), 6.89 (s, 1H), 6.86 (d, J = 7.0 Hz, 2H), 6.83 (d, J = 2.0 Hz, 2H), 6.79 (s, 1H), 6.68 (s, 1H), 6.63 (s, 1H), 6.29 (s, 1H), 5.05 (d, J = 6.5 Hz, 1H), 3.85–3.78 (m, 6H), 3.76 (m, 4H), 3.73–3.69 (m, 16H), 3.67 (s, 6H), 2.90 (ddd, J = 14.0, 7.0, 3.0 Hz, 1H), 2.65 (dd, J = 13.5, 7.5 Hz, 1H), 2.52 (dd, J = 13.5, 3.5 Hz, 1H).13 C NMR(126MHz,CDCl 3 ,298K)δ200.4,157.5,151.0,150.9,150.8,150.8,150.7,150.5,150.2,135.4,133.3,132.6,132.0,129.2,129.0,128.8,128.6,128.1,127.9,127.8,127.6,127.6,127.1,126.0,125.7,125.2,114.8,114.4,114.4,114.3,114.0,114.0,113.7,113.0,56.1,56.0,55.9,55.9,55.8,55.6,53.2,51.9,45.1,30.2,29.5,29.3,28.8,26.4.HRMS(ESI)of 1b:calcdfor C 53 H 54 NO 10 + [M+H] + =864.3743,found m / z=864.3721.

[0081] Example 3

[0082] Same as Example 1, except that R is

[0083] Compound 1c: Separated by column chromatography, eluent: ethyl acetate / dichloromethane (1:99), obtained as a pale yellow solid, yield 33%. 1 H NMR(500MHz,CDCl 3 ,298K)δ7.80(s,OH),7.55(dd,J=7.5,1.5Hz,2H),7.46(d,J=8.5Hz,2H),7.43(t,J=7.5Hz,2H),7.34(t,J=7.5Hz,1H),7.2(s,2H),6.90(s,1H),6.84(m,4H),6.79(s,1H),6.70(d,J=14.5Hz,2H),6.26(s,1H),4.94(d,J=6.5Hz,1H),3.85–3.77(m,8H),3.75(d,J=6.0Hz,6H),3.71(m,11H),3.70–3.67(m,7H),2.83(td,J=7.0,3.0Hz,1H),2.69(dd,J=13.5,7.0Hz,1H),2.49(dd,J=13.4,3.0Hz,1H). 1313C NMR (126 MHz, CDCl 3 ) δ 200.4, 157.6, 151.1, 150.9, 150.7, 150.5, 150.2, 140.8, 134.0, 136.9, 131.9, 129.3, 129.2, 128.9, 128.7, 128.6, 128.1, 127.9, 127.7, 127.2, 127.1, 125.2, 114.7, 114.5, 114.4, 114.4, 114.0, 113.8, 113.1, 77.3, 56.2, 56.0, 55.9, 55.9, 55.8, 55.8, 55.6, 53.3, 52.0, 44.7, 30.3, 29.7, 29.4, 29.2, 28.8, 26.3. HRMS(ESI) of 1c: calcd for C 55 H 56 NO 10 + [M + H] + = 890.3899, found m / z = 890.3877.

[0084] Example 4

[0085] Same as Example 1, except that R is

[0086] Compound 1d: Separated by column chromatography, eluent: ethyl acetate / dichloromethane (1:99), obtained as a pale yellow solid, yield 91%. 1 1H NMR (500 MHz, CDCl 3 , 298 K) δ 8.86 (s, OH), 7.15 (dd, J = 8.5, 5.0 Hz, 2H), 6.93 (s, 1H), 6.92 (d, J = 5.0 Hz, 2H), 6.90 (d, J = 5.0 Hz, 2H), 6.88 (t, J = 10.0 Hz, 2H), 6.83 (s, 1H), 6.69 (s, 1H), 6.65 (s, 1H), 6.29 (s, 1H), 4.93 (d, J = 5.0 Hz, 1H), 3.88–3.82 (m, 6H), 3.79–3.76 (m, 12H), 3.73 (m, 10H), 3.69 (m, 4H), 2.84 (td, J = 7.0, 2.5 Hz, 1H), 2.66 (dd, J = 13.5, 7.0 Hz, 1H), 2.48 (dd, J = 13.5, 3.0 Hz, 1H). 13 13C NMR (126 MHz, CDCl 3, 298 K) δ 200.5, 162.8, 160.9, 157.3, 151.0, 150.9, 150.8, 150.7, 150.6, 150.4, 150.1, 133.5, 132.0, 130.4, 130.3, 129.2, 129.1, 128.8, 128.5, 128.1, 127.9, 127.6, 125.0, 115.3, 115.6, 114.8, 114.3, 114.1, 114.0, 113.8, 113.6, 112.9, 77.4, 56.0, 55.9, 55.8, 55.8, 55.6, 52.9, 51.9, 44.3, 30.1, 29.5, 29.1, 28.8, 26.2. HRMS(ESI) of 1d: calcd for C 49 H 51 FNO 10 + [M + H] + =832.3492, found m / z =890.3458.

[0087] Example 5

[0088] Same as Example 1, except that R is

[0089] Compound 1e: Separated by column chromatography, eluent: ethyl acetate / dichloromethane (1:99), obtained as a pale yellow solid, yield 53%. 1 H NMR(500 MHz, CDCl 3 , 298 K) δ 8.21(s, OH), 7.09(d, J = 8.5 Hz, 2H), 6.91(s, 1H), 6.82(dd, J = 11.0, 4.0 Hz, 4H), 6.78(s, 1H), 6.71(d, J = 12.0 Hz, 2H), 6.62(d, J = 8.5 Hz, 2H), 6.20(s, 1H), 4.81(d, J = 6.5 Hz, 1H), 3.87–3.79(m, 6H), 3.75–3.71(m, 24H), 3.65–3.59(m, 2H), 2.91(s, 6H), 2.75(td, J = 7.0, 3.0 Hz, 1H), 2.63(dd, J = 13.5, 7.0 Hz, 1H), 2.46(dd, J = 13.5, 3.0 Hz, 1H). 13 C NMR(126 MHz, CDCl 3,298K) δ 200.8, 158.1, 151.1, 151.0, 150.9, 150.8, 150.7, 150.5, 150.2, 149.6, 131.9, 129.5, 129.2, 129.0, 128.6, 128.3, 128.1, 127.7, 125.6, 125.4, 114.9, 114.4, 114.4, 114.0, 114.0, 113.8, 113.1, 112.6, 77.3, 56.2, 56.1, 56.0, 56.0, 55.9, 55.8, 55.7, 53.0, 52.4, 44.3, 40.6, 30.3, 29.5, 29.0, 28.9, 26.3. HRMS(ESI) of 1e: calcd for C 51 H 57 N 2 O 10 + [M + H] + = 857.4008, found m / z = 857.4012.

[0090] Example 6

[0091] Same as Example 1, except that R is

[0092] 1f: Column chromatography separation, eluent: ethyl acetate / dichloromethane (1:99), obtained a pale yellow solid, yield 61%. 1 H NMR(500 MHz, CDCl 3 , 298K) δ 8.46(s, OH), 7.15(d, J = 8.5 Hz, 2H), 6.93(s, 1H), 6.88(t, J = 5.0, 3H), 6.80(d, J = 13.0 Hz, 2H), 6.75(d, J = 15.5 Hz, 2H), 6.67(s, 1H), 6.24(s, 1H), 4.88(d, J = 6.5 Hz, 1H), 3.83–3.80(m, 6H), 3.77–3.68(m, 29H), 2.78(t, J = 7.0 Hz, 1H), 2.62(dd, J = 13.5, 7.0 Hz, 1H), 2.45(d, J = 13.0 Hz, 1H). 13 C NMR(126 MHz, CDCl 3, 298 K) δ 200.7, 158.6, 157.8, 151.0, 150.9, 150.8, 150.8, 150.7, 150.6, 150.4, 150.1, 131.9, 129.9, 129.1, 129.0, 128.7, 128.5, 128.1, 128.1, 127.8, 125.3, 114.8, 114.3, 114.1, 114.0, 113.9, 113.8, 113.6, 112.9, 77.3, 56.0, 56.0, 55.9, 55.8, 55.8, 55.6, 55.1, 53.1, 52.3, 44.4, 30.2, 29.5, 28.9, 28.7, 26.1. HRMS(ESI) of 1f: calcd for C 50 H 54 NO 11 + [M + H] + =844.3692, found m / z=844.3682.

[0093] Example 7

[0094] Same as Example 1, except that R is

[0095] Compound 1g: Separated by column chromatography, eluent: ethyl acetate / dichloromethane (1:99), obtained as a pale yellow solid, yield 65%. 1 H NMR(500 MHz, CDCl 3 , 298 K) δ 7.91(s, OH), 6.89(s, 1H), 6.84(s, 1H), 6.82(s, 3H), 6.79(d, J = 12.0 Hz, 2H), 6.70(s, 1H), 6.12(s, 1H), 5.60(s, J = 17.0, 10.0, 7.5 Hz, 1H), 5.21(dd, J = 34.0, 17.0 Hz, 2H), 4.47(dd, J = 8.0, 5.5 Hz, 1H), 3.85–3.78(m, 6H), 3.76–3.71(m, 16H), 3.69–3.67(m, 10H), 2.98(dd, J = 13.5, 7.5 Hz, 1H), 2.57–2.52(m, 2H). 13 C NMR(126 MHz, CDCl 3, 298 K) δ 200.3, 156.9, 151.0, 150.9, 150.7, 150.4, 150.3, 149.3, 132.3, 131.2, 129.1, 128.9, 128.8, 128.6, 128.1, 128.1, 127.7, 125.3, 118.8, 114.5, 114.4, 114.3, 114.3, 114.0, 113.9, 113.7, 113.2, 56.2, 56.1, 55.9, 55.9, 55.8, 55.8, 55.6, 53.3, 51.5, 43.6, 30.2, 29.5, 28.8, 26.0. HRMS(ESI) of 1g: calcd for C 45 H 50 NO 10 + [M + H] + =764.3430, found m / z =764.3059.

[0096] Example 8

[0097] Same as Example 1, except that R is

[0098] Compound 1h: Separated by column chromatography, eluent was ethyl acetate / dichloromethane (1:99), obtained as a pale yellow solid, yield 78%. 1 H NMR(500 MHz, CDCl 3 , 298 K) δ 8.42(s, OH), 6.98(s, 1H), 6.88(d, J = 5.0 Hz, 2H), 6.86(s, 1H), 6.85(d, J = 4.5 Hz, 2H), 6.75(d, J = 7.0 Hz, 2H), 6.67(s, 1H), 6.29(s, 1H), 5.91(d, J = 3.5 Hz, 1H), 5.87(s, 1H), 5.13(d, J = 6.0 Hz, 1H), 3.82–3.79(m, 6H), 3.76–3.72(m, 16H), 3.70–3.68(m, 10H), 2.89(dd, J = 13.5, 6.5 Hz, 1H), 2.68(td, J = 6.2, 2.9 Hz, 1H), 2.60(dd, J = 13.5, 3.0 Hz, 1H). 13 C NMR(126 MHz, CDCl 3,298K) δ 199.5, 155.2, 150.9, 150.8, 150.8, 150.7, 150.6, 150.4, 150.2, 149.6, 141.3, 131.4, 129.1, 129.0, 128.8, 128.5, 128.1, 127.9, 127.6, 124.9, 114.7, 114.2, 114.1, 113.9, 113.8, 113.7, 113.0, 109.9, 107.7, 56.1, 55.9, 55.9, 55.8, 55.6, 53.1, 50.9, 38.4, 30.0, 29.5, 29.2, 28.8, 25.8. HRMS(ESI) of 1h: calcd for C 47 H 50 NO 11 + [M + H] + =804.3379, found m / z=804.3353.

[0099] Example 9

[0100] Same as Example 1, except that R is

[0101] Compound 1i: Separated by column chromatography, eluent: ethyl acetate / dichloromethane (1:99), obtained as a pale yellow solid, yield 79%. 1 H NMR(500MHz, CDCl 3 , 298K) δ 8.78(s, OH), 6.92(d, J=3.5Hz, 2H), 6.89(s, 1H), 6.87(d, J=6.0Hz, 2H), 6.77(d, J=2.5Hz, 2H), 6.76(d, J=7.0Hz, 1H), 6.73(d, J=3.5Hz, 1H), 6.66(s, 1H), 6.56(t, J=3.5Hz, 1H), 6.34(s, 1H), 5.34(d, J=5.5Hz, 1H), 3.85–3.80(m, 6H), 3.78–3.75(m, 16H), 3.71(m, 7H), 3.65(s, 3H), 2.90(dd, J=13.5, 6.5Hz, 1H), 2.79(td, J=6.0, 2.5Hz, 1H), 2.69(dd, J=13.5, 3.0Hz, 1H). 13 C NMR(126MHz, CDCl 3, 298K) δ 199.9, 156.7, 151.0, 150.8, 150.8, 150.6, 150.5, 150.2, 149.8, 138.9, 131.4, 129.1, 128.9, 128.8, 128.5, 128.1, 128.0, 127.5, 126.0, 126.0, 124.7, 124.0, 114.8, 114.2, 114.1, 114.0, 113.9, 113.7, 112.9, 77.3, 56.1, 56.0, 55.9, 55.9, 55.8, 55.5, 52.9, 52.1, 39.8, 30.0, 29.5, 29.3, 28.9, 26.0. HRMS(ESI) of 1i: calcd for C 47 H 50 NO 10 S + [M + H] + = 820.3150, found m / z = 820.3144.

[0102] Example 10

[0103] Same as Example 1, except that R is

[0104] Compound 1j: Column chromatography separation, eluent was ethyl acetate / dichloromethane (1:99), obtained a pale yellow solid, yield 28%. Column chromatography (EtOAc / DCM = 1:99 (v / v) afforded 3j as a pale yellow solid (88mg, 28% yield). 1 1H NMR (500 MHz, CDCl 3 , 298K) δ 7.61 (s, OH), 6.88 (d, J = 7.5 Hz, 2H), 6.82 (d, J = 2.0 Hz, 2H), 6.80 (m, 3H), 6.69 (s, 1H), 6.04 (d, J = 1.5 Hz, 1H), 3.85–3.75 (m, 10H), 3.73 (d, J = 5.0 Hz, 6H), 3.71 (s, 3H), 3.68 (m, 10H), 3.65 (s, 3H), 3.39 (dd, J = 9.0, 4.5 Hz, 1H), 3.12 (dd, J = 13.5, 8.5 Hz, 1H), 2.76 (dd, J = 13.5, 2.0 Hz, 1H), 2.63 (m, 1H), 0.53 (m, 1H), 0.43 (m, 1H), 0.35 (m, 2H), 0.13 (m, 1H). 1313C NMR(126MHz,CDCl 3 ,298K)δ199.7,157.6,149.4,149.3,149.2,148.9,148.7,148.3,129.6,127.6,127.3,127.1,127.0,126.6,126.5,126.2,124.0,113.4,112.8,112.8,112.7,112.4,112.2,111.6,54.6,54.6,54.4,54.3,54.3,54.2,54.0,51.7,51.6,41.5,30.0,28.6,28.2,28.0,27.4,27.1,25.2,9.7,4.2,0.0.HRMS(ESI)of 1j:calcd for C 46 H 52 NO 10 + [M+H] + =778.3586,found m / z=778.3561.

[0105] Example 11

[0106] Same as Example 1, except that R is

[0107] Compound 1k: Separated by column chromatography, eluent was ethyl acetate / dichloromethane (1:99), obtained as a pale yellow solid, yield 24%. 1 1H NMR(500MHz,CDCl 3 ,298K)δ7.22(d,J=2.0Hz,1H),7.02(s,1H),6.94(s,1H),6.86(s,2H),6.68(s,1H),6.59(s,1H),6.54(s,1H),3.84–3.93(m,7H),3.77(m,10H),3.74(d,J=7.0Hz,7H),3.62(m,8H),3.29(d,J=16.0Hz,1H),2.86(d,J=13.0Hz,1H),2.66(d,J=16.5Hz,1H),2.49(dd,J=13.5,6.0Hz,2H),2.34(m,1H),1.79(m,3H),1.62(m,3H),1.24(m,1H). 13 13C NMR(126MHz,CDCl 3,298K) δ 199.2, 154.8, 152.1, 151.8, 151.5, 151.2, 150.9, 150.4, 150.0, 139.7, 130.2, 129.6, 129.5, 129.4, 129.2, 128.0, 126.9, 126.2, 122.3, 114.7, 114.4, 114.3, 114.2, 113.9, 113.6, 113.5, 111.1, 56.3, 56.3, 56.1, 56.0, 56.0, 55.9, 55.8, 53.4, 53.1, 48.1, 43.5, 42.3, 36.4, 29.9, 29.7, 29.2, 28.0, 27.0, 27.0, 26.3, 25.8. HRMS(ESI) of 1k: calcd for C 48 H 56 NO 10 + [M + H] + =806.3899, found m / z = 806.3872.

[0108] Example 12

[0109] Same as Example 1, except that R is

[0110] Compound 1l: Separated by column chromatography, eluent: ethyl acetate / n - hexane (50:50), obtained as a pale yellow solid, yield 22%. 1 H NMR(500MHz, CDCl 3 , 298K) δ 7.93(s, OH), 6.92(d, J = 3.0Hz, 2H), 6.88(d, J = 8.0Hz, 2H), 6.80(d, J = 3.5Hz, 2H), 6.78(s, 1H), 6.70(s, 1H), 6.10(d, J = 1.5Hz, 1H), 3.84–3.77(m, 8H), 3.74(m, 8H), 3.72(m, 6H), 3.70–3.68(m, 10H), 3.00(dd, J = 13.0, 8.0Hz, 1H), 2.81(dd, J = 13.0, 2.0Hz, 1H), 2.62(m, 1H), 1.73(m, 1H), 1.57(m, 1H), 1.40(m, 1H), 1.24(m, 2H), 1.05(m, 4H), 0.67(m, 1H), 0.53(m, 2H). 13 C NMR(126MHz, CDCl 3, 298 K) δ 201.1, 158.9, 151.6, 151.0, 150.8, 150.8, 150.6, 150.5, 150.4, 150.3, 131.3, 129.0, 128.6, 128.5, 128.5, 128.1, 127.6, 125.5, 115.1, 114.4, 114.1, 113.9, 113.9, 113.1, 56.1, 56.0, 55.8, 55.8, 55.7, 55.6, 53.3, 51.9, 45.5, 38.8, 33.6, 30.8, 30.2, 29.4, 29.2, 28.6, 26.8, 26.3, 25.9. HRMS(ESI) of 1l: calcd for C 49 H 58 NO 10 + [M + H] + = 820.4056, found m / z = 820.4031.

[0111] Example 13

[0112] Same as Example 1, except that R is

[0113] Compound 1m: Separated by column chromatography, eluent was ethyl acetate / dichloromethane (5:95), obtained as a pale yellow solid, yield 52%. 1 H NMR(500 MHz, CDCl 3 , 298 K) δ 8.33 (s, OH), 6.90 (s, 1H), 6.85–6.81 (m, 6H), 6.67 (s, 1H), 6.06 (s, 1H), 3.77–3.66 (m, 32H), 2.95 (dd, J = 13.5, 8.0 Hz, 1H), 2.56 (ddd, J = 13.5, 11.5, 2.5 Hz, 2H), 1.05 (d, J = 7.0 Hz, 3H), 0.87 (m, 1H). 13 C NMR(126 MHz, CDCl 3,298K) δ 201.3, 160.5, 151.0, 150.9, 150.8, 150.8, 150.6, 150.4, 150.2, 148.6, 131.1, 129.0, 129.0, 128.7, 128.5, 128.1, 128.0, 127.8, 125.5, 114.6, 114.3, 114.2, 114.1, 114.0, 113.8, 113.7, 113.1, 56.1, 56.1, 55.9, 55.9, 55.8, 55.6, 53.1, 52.2, 34.2, 30.2, 29.5, 28.9, 28.4, 25.8, 12.8. HRMS(ESI) of 1m: calcd for C 44 H 50 NO 10 + [M + H] + =752.3430, found m / z=752.3483.

[0114] Example 14

[0115] Same as Example 1, except that R is

[0116] Compound 1n: Separated by column chromatography, eluent is ethyl acetate / dichloromethane (40:60), obtained a pale yellow solid, yield 38%. 1 H NMR(500 MHz, CDCl 3 , 298K) δ 8.01(s, OH), 6.86(d, J = 5.5 Hz, 2H), 6.83(d, J = 9.5 Hz, 2H), 6.81(s, 2H), 6.79(s, 1H), 6.73(s, 1H), 6.05(s, 1H), 3.83–3.67(m, 32H), 3.00(dd, J = 13.0, 8.5 Hz, 1H), 2.69(dd, J = 13.0, 1.5 Hz, 1H), 2.66(m, 1H), 1.87(m, 1H), 1.06(d, J = 7.0 Hz, 3H), 0.89(m, 1H), 0.79(d, J = 7.0 Hz, 3H). 13 C NMR(126 MHz, CDCl 3,298K) δ 201.3, 159.0, 151.1, 151.0, 150.9, 150.8, 150.6, 150.6, 150.4, 150.1, 131.5, 129.0, 128.9, 128.7, 128.6, 128.0, 127.7, 125.8, 114.8, 114.4, 114.3, 114.3, 113.9, 113.9, 113.7, 113.0, 56.2, 56.1, 56.0, 55.9, 55.8, 55.8, 55.7, 55.6, 53.1, 31.6, 30.2, 29.5, 29.2, 28.8, 28.4, 27.5, 23.6, 22.7, 21.2, 14.2. HRMS(ESI) of 1n: calcd for C 46 H 54 NO 10 + [M + H] + =780.3743, found m / z =780.3729.

[0117] Example 15

[0118] Same as Example 1, except that R is

[0119] Compound 1o: Separated by column chromatography, eluent: ethyl acetate / dichloromethane (1:99), obtained as a pale yellow solid, yield 33%. 1 H NMR(500MHz, CDCl 3 , 298K) δ 8.00(s, OH), 6.89(s, 1H), 6.85(s, 1H), 6.83(d, J = 2.0Hz, 2H), 6.82–6.81(m, 3H), 6.73(s, 1H), 6.08(s, 1H), 3.83–3.76(m, 10H), 3.74(d, J = 3.0Hz, 1H), 3.72(s, 6H), 3.69(m, 10H), 2.98(dd, J = 13.0, 7.5Hz, 1H), 2.58(dd, J = 13.0, 2.0Hz, 1H), 2.53(m, 1H), 1.25(m, 2H), 1.16(m, 4H), 0.80(m, 1H), 0.78(t, J = 7.0Hz, 3H). 13 C NMR(126MHz, CDCl 3,298K) δ 201.3, 159.7, 151.0, 150.9, 150.7, 150.7, 150.4, 150.2, 149.6, 130.9, 129.0, 128.9, 128.8, 128.5, 128.2, 128.0, 127.7, 125.7, 114.6, 114.4, 114.3, 113.9, 113.9, 113.7, 113.2, 56.2, 56.0, 55.9, 55.9, 55.8, 55.8, 55.6, 53.1, 52.4, 39.7, 30.2, 29.7, 29.5, 28.9, 28.8, 28.6, 26.7, 22.9, 14.0. HRMS(ESI) of 1o: calcd for C 44 H 50 NO 10 + [M + H] + =794.3899, found m / z =780.3880.

[0120] Example 16

[0121] Same as Example 1, except that R is

[0122] Compound 1p: Separated by column chromatography, eluent was ethyl acetate / dichloromethane (1:99), obtained as a pale yellow solid, yield 32%. 1 H NMR(500 MHz, CDCl 3 , 298K) δ 8.00(s, OH), 6.89(s, 1H), 6.84–6.81(m, 6H), 6.73(s, 1H), 6.07(d, J = 1.0 Hz, 1H), 3.83–3.76(m, 10H), 3.73(d, J = 3.0 Hz, 6H), 3.71(d, J = 3.0 Hz, 6H), 3.69–3.66(m, 10H), 2.96(dd, J = 13.0, 8.0 Hz, 1H), 2.55(dd, J = 13.5, 2.5 Hz, 1H), 2.52–2.49(m, 1H), 1.26–1.24(m, 2H), 1.23–1.13(m, 8H), 0.88(t, J = 3.5 Hz, 1H), 0.82(t, J = 7.0 Hz, 3H). 13 C NMR(126 MHz, CDCl 3,298K) δ 201.3, 159.6, 151.0, 150.9, 150.8, 150.6, 150.4, 150.2, 149.6, 130.9, 129.0, 128.9, 128.8, 128.5, 128.3, 128.0, 127.7, 125.8, 114.8, 114.5, 114.3, 113.9, 113.9, 113.7, 113.2, 56.2, 56.1, 55.9, 55.9, 55.8, 55.8, 55.6, 53.1, 52.6, 39.7, 31.7, 30.2, 29.7, 29.5, 29.1, 28.8, 28.5, 27.6, 26.7, 22.6, 14.1. HRMS(ESI) of 1p: calcd for C 49 H 60 NO 10 + [M + H] + = 822.4212, found m / z = 822.4241.

[0123] Example 17

[0124] Same as Example 1, except that 1.5 mmol of Grignard reagent was added slowly.

[0125] Example 18

[0126] Same as Example 1, except that 1.8 mmol of Grignard reagent was added slowly.

[0127] Example 19

[0128] Same as Example 1, except that 2.0 mmol of Grignard reagent was added slowly.

[0129] Example 20

[0130] Same as Example 1, except that 3.0 mmol of Grignard reagent was added slowly.

[0131] Example 21

[0132] Same as Example 1, except that the reaction was carried out at low temperature for 40 minutes.

[0133] Example 22

[0134] Same as Example 1, except that the reaction was carried out at low temperature for 50 minutes.

[0135] Example 23

[0136] Same as Example 1, except that the reaction was carried out at low temperature for 60 minutes.

[0137] Pillar[n]arenes are a class of rigid supramolecular macrocyclic structures with a certain cavity and a column-like symmetry. The cavity itself has the property of being electron-rich and can selectively recognize and capture positively charged guest molecules or groups and neutral molecules (Chem. 2018, 4, 2029). Since the discovery of pillar arenes, due to their simple synthesis, easy modification, and special host-guest molecular recognition properties, pillar arenes have quickly become a generation of star macrocyclic molecules full of potential. Pillar[n]arene[1]benzoquinone oxime is a modification strategy for the ortho-functionalization of pillar arenes, and derivatives of pillar[n]arene[1]benzoquinone oxime with ortho-functionalization will be obtained. Such derivatives have significant differences in structure and cavity characteristics from pillar[n]arenes or pillar[n]arene[1]benzoquinone oxime. In 2018, Professor Huang Feihe of Zhejiang University reported non-porous adaptive crystals, which are mainly a novel adsorption and separation material based on pillar[n]arenes and have potential application value in the chemical industry (Science China: Chemistry, 2019, 49, 832). It is mainly the application of pillar arenes as non-porous adaptive crystals in the separation and purification of ethylene / ethylbenzene, p-xylene purification, 1-pentene / 2-pentene separation, methylcyclohexane / toluene separation, iodine adsorption, etc. The pillar[n]arene[1]benzoquinone oxime and its derivatives obtained in the present invention have similar properties in terms of structure and cavity properties, and one of the benzene rings in this type of structure is de-aromatic. According to the principle of similar solubility, it can also be used to separate similar hydrocarbons.

[0138] The above is only an illustration of the best embodiments of the present invention and should not be construed as a limitation of the claims. The present invention is not limited to the above embodiments, and its specific structure allows for changes. Any changes made within the protection scope of the independent claims of the present invention are within the protection scope of the present invention.

Claims

1. A pillar[n]arene benzoquinone oxime ortho-functionalized derivative, characterized in that: The general structure is as follows: Here, n is 4 or 5.

2. A method for preparing the ortho-functionalized derivative of pillar[n]arene benzoquinone oxime as claimed in claim 1, characterized in that: The invention discloses a method for preparing a column[n]arene[1]benzoquinone oxime by reacting the column[n]arene[1]benzoquinone oxime with a Grignard reagent to obtain an ortho-functionalized derivative of the column[n]arene benzoquinone oxime.

3. The method for preparing the ortho-functionalized derivative of pillar[n]arene benzoquinone oxime according to claim 2, characterized in that: The reaction site of pillar[n]arene[1]benzoquinone oxime with the Grignard reagent occurs at the ortho position of pillar[n]arene[1]benzoquinone oxime.

4. The method for preparing the ortho-functionalized derivative of pillar[n]arene benzoquinone oxime according to claim 2, characterized in that: The specific process is as follows: Under nitrogen protection, a Grignard reagent solution is added to a solution of column[n]arene[1]benzoquinone oxime, and the reaction is carried out at low temperature until the color of the reaction solution changes from yellow to red, and then post-treatment is performed to obtain an ortho-functionalized derivative of column[n]arene benzoquinone oxime.

5. The method for preparing the ortho-functionalized derivative of pillar[n]arene benzoquinone oxime according to claim 2, characterized in that: The molar ratio of column[n]arene[1]benzoquinone oxime to Grignard reagent is 0.4mmol:1.5-3.0mmol.

6. The method for preparing the ortho-functionalized derivative of pillar[n]arene benzoquinone oxime according to claim 2, characterized in that: The Grignard reagent has the chemical formula RMgBr, and the R group is methyl, ethyl, propyl, butyl, n-pentyl, n-hexyl, isopropyl, cyclopropyl, cyclopentyl, cyclohexyl, thiophene, furan, substituted olefins, p-methoxyphenyl, 4-fluorophenyl, phenyl, naphthyl or biphenyl.

7. The method for preparing the ortho-functionalized derivative of pillar[n]arene benzoquinone oxime according to claim 2, characterized in that: The reaction temperature was minus 78°C.

8. The method for preparing the ortho-functionalized derivative of pillar[n]arene benzoquinone oxime according to claim 2, characterized in that: The reaction time is 30-60 minutes.

9. The method for preparing the ortho-functionalized derivative of pillar[n]arene benzoquinone oxime according to claim 2, characterized in that: The specific process of post-treatment is: pouring the reaction solution into a saturated ammonium chloride solution, separating the organic phase, drying, and then concentrating under reduced pressure, and separating by column chromatography to obtain column [n] aromatic hydrocarbon benzoquinone oxime ortho-functionalized derivatives.

10. The method for preparing the ortho-functionalized derivative of pillar[n]arene benzoquinone oxime according to claim 9, characterized in that: The solvent in the solution of column[n]arene[1]benzoquinone oxime is tetrahydrofuran.

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