A novel anion detection reagent and its application

Abstract

The present invention discloses a novel anion detection reagent and its application. The anion detection reagent is a symmetric molecular cage and its derivatives, and the structural formula is shown in Formula I. It can be prepared by an intermolecular cage formation reaction of the compounds shown in Formula II and Formula III through a 1+1 fragment method. The present invention selects cheap and easily available raw materials, and can rapidly and massively prepare the compounds shown in Formula I, Formula II, Formula III and Formula IV from simple raw materials through reactions such as nucleophilic substitution and hydrogenation reduction. The reaction conditions are mild. The compound shown in Formula I is stable in air and is easy to purify and separate, and can be used as an anion detection reagent, having good application prospects.

Description

Technical Field

[0001] The present invention relates to a novel anion detection reagent and its application, belonging to the technical field of anion recognition. Background Art

[0002] Anions play an important role in the life process. The nucleic acid molecule, which is the essence of the genetic material of life, is essentially an anion, and it is closely related to people's physical functions. For example, iodide ions affect the production of thyroid hormones, the content of fluoride ions is closely related to dental health, the disorder of chloride ion channel function will cause cystic fibrosis symptoms, and carbonate ions play a crucial role in the pH regulation of the human body. In addition, anions are also used in surfactants and phase transfer catalysts, etc. Therefore, the study of anion recognition is of great significance (Smith, A. E. Cell. 1993, 73, 1251 - 1254; Featherstone, J. D. B. Community Dent Oral. 1999, 27, 31 - 40; Kleerekoper, M. Endoccrin Metab Clin. 1998, 27, 441; Delange, F. Thyroid. 1994, 4, 107 - 128.). However, the strong solvation effect, complex shape, and large size of anions usually make the recognition of anions, especially complex anions, very challenging (Beer, P. D. Ange Chem Int Ed. 2014, 53, 11716 - 11754).

[0003] Thiourea is a kind of excellent functional group for anion recognition and is widely used in bonding and catalysis research (Schreiner, P. R. Chem. Soc. Rev. 2009, 38, 1187 - 1198; Wu, B. Chem. Commun. 2016, 52, 9614 - 9627; Nagasawa, K. Tetrahedron Lett. 2004, 45, 5589 - 5592.). Thiourea has a pair of almost parallel hydrogen - bond donors and has good recognition ability for a series of anions with different geometries through bidentate or monodentate modes, such as spherical halide ions, triangular carboxylate ions, tetrahedral sulfonate ions and phosphate ions, etc. In addition, thiourea can also recognize neutral molecules such as aldehydes, ketones and imines and has good applications in catalysis. The thiocarbonyl group of thiourea can act as a hydrogen - bond acceptor to participate in the formation of intramolecular or intermolecular hydrogen bonds and construct a multiple hydrogen - bond network. Based on the additivity and cooperativity of hydrogen bonds, multiple thiourea groups can be introduced into the same molecule to develop cooperative recognition and catalytic systems, improving the recognition ability for anions and catalytic efficiency (Jacobsen, E. N. J. Am. Chem. Soc. 2016, 138, 13525 - 13528; Bobal, P. J. Org. Chem. 2017, 82, 8342 - 8358.). Summary of the Invention

[0004] The object of the present invention is to provide a novel anion detection reagent which is stable in air and easy to purify and separate and has good application prospects.

[0005] The anion detection reagent provided by the present invention is shown as formula Ⅰ:

[0006]

[0007] In the formula, R is selected from any one of the following groups: -H, -OH, -CH3, -C2H5, -CH2CH2CH3; X is selected from any one of the following groups: -COO-, -p - PhO- and -p - Ph - N(CH3)-.

[0008] The present invention provides a preparation method of the symmetric molecular cage and its derivatives shown in formula Ⅰ, including the following steps:

[0009] In the presence of a base, the compound shown in formula Ⅱ reacts with the compound shown in formula Ⅲ to obtain the product.

[0010]

[0011] In the formula, R is selected from any one of the following groups: -H, -OH, -CH3, -C2H5, and -CH2CH2CH3; X is selected from any one of the following groups: -COO-, -p-PhO-, and -p-Ph-N(CH3)-.

[0012] The reaction equation for constructing the aromatic ring between the compound shown in Formula II and the compound shown in Formula III is as follows:

[0013]

[0014] In the above preparation method, the base can be any one of triethylamine, DMAP (4-dimethylaminopyridine), DIPEA (diisopropylethylamine), and pyridine;

[0015] The solvent for the reaction is any one of N,N-dimethylformamide, dimethyl sulfoxide, pyridine, and acetonitrile;

[0016] The molar ratio of the compound shown in Formula II, the compound shown in Formula III, and the base is 1:1:3 to 12;

[0017] The temperature of the reaction is -20 to 80 °C, and the time is 3 to 72 h.

[0018] Among them, the starting materials, the compound shown in Formula II and the compound shown in Formula III, also fall within the protection scope of the present invention.

[0019] The present invention also provides a simple and efficient method for constructing the compound shown in Formula II and the compound shown in Formula III, and the reaction equation is as follows:

[0020] First, the preparation method of the compound shown in Formula IV includes the following steps:

[0021] In the presence of a base and a condensing agent, the compound shown in Formula V reacts with 3-nitro-5-trifluoromethylbenzyl alcohol or 3-nitro-5-trifluoromethylbenzyl bromide to obtain the product;

[0022]

[0023] In the formula, R is selected from any one of the following groups: -H, -OH, -CH3, -C2H5, and -CH2CH2CH3; X is selected from any one of the following groups: -COO-, -p-PhO-, and -p-Ph-N(CH3)-.

[0024] In the above preparation method, the base is any one of triethylamine, 4-dimethylaminopyridine, diisopropylethylamine, pyridine, potassium carbonate, and sodium carbonate;

[0025] The condensing agent can be any one of dicyclohexylcarbodiimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, 2-(7-azabenzotriazol)-N,N,N',N'-tetramethyluronium hexafluorophosphate, and benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate;

[0026] The solvent for the reaction can be at least one of tetrahydrofuran, dichloromethane, ethyl acetate, acetone, acetonitrile, and methanol;

[0027] The temperature of the reaction can be -20 to 80 °C, and the time can be 3 to 96 h;

[0028] The molar ratio of the compound shown in Formula V to the 3-nitro-5-trifluoromethylbenzyl alcohol or the 3-nitro-5-trifluoromethylbenzyl bromide is 1:3 to 6:3 to 6.

[0029] The compound shown in Formula IV also belongs to the protection scope of the present invention.

[0030] The preparation method of the compound shown in Formula III includes the following steps:

[0031] In the presence of a reducing agent, the compound shown in Formula IV is obtained through a reduction reaction;

[0032] The reducing agent is stannous chloride or palladium on carbon;

[0033] The solvent for the reduction reaction is any one of tetrahydrofuran, dichloromethane, ethyl acetate, and acetonitrile;

[0034] The molar ratio of the compound shown in Formula IV to the reducing agent is 1:3 to 12;

[0035] The temperature of the reduction reaction is -20 to 80 °C, and the time is 3 to 96 h.

[0036] The preparation method of the compound shown in Formula II includes the following steps:

[0037] The compound shown in Formula III reacts with 1,1'-thiocarbonyldiimidazole to obtain it;

[0038] The solvent for the reaction is any one of tetrahydrofuran, acetonitrile, dichloromethane, N,N-dimethylformamide, and dimethyl sulfoxide;

[0039] The molar ratio of the compound of Formula III to the 1,1'-thiocarbonyldiimidazole is 1:3 to 12;

[0040] The temperature of the reaction is -20 to 80 °C, and the time is 3 to 96 h.

[0041] The symmetric molecular cage shown in Formula I and its derivatives provided by the present invention can be used in anion recognition,

[0042] The anions include inorganic anions and organic anions;

[0043] The inorganic anions are fluoride ions, chloride ions, bromide ions or iodide ions;

[0044] The organic anions are monocarboxylate ions, monosulfonate ions, tricarboxylate ions, trisulfonate ions or phosphate ions.

[0045] The present invention selects inexpensive and easily available raw materials. Through simple esterification, reduction reactions from 3-nitro-5-trifluoromethylbenzyl alcohol and trimesic acid compounds, or through nucleophilic substitution and hydrogenation reduction reactions from 3-nitro-5-trifluoromethylbenzyl bromide and aromatic phenol compounds, etc., a large number of fragment II structures and III structures can be rapidly prepared. Further, by using the intermolecular addition and cage formation reaction of II and III, symmetric molecular cages and their derivatives can be rapidly prepared. The reaction conditions are mild, the obtained compounds are stable in air and easy to purify and separate, and have good application prospects. Description of the Drawings

[0046] Figure 1 1H NMR titration spectrum of the compound shown in Formula Ia with chloride ions (298K, CD3CN, 400 MHz). Detailed Description of the Invention

[0047] The experimental methods used in the following examples are all conventional methods unless otherwise specified.

[0048] The materials, reagents, etc. used in the following examples can be obtained from commercial channels unless otherwise specified.

[0049] Example 1: Preparation of the ester group-linked arm compound shown in the general formula of Structure IVa (R is hydrogen)

[0050] The reaction formula is as follows:

[0051]

[0052] Add trimellitic acid (1.58 g, 7.5 mmol), 3-nitro-5-(trifluoromethyl)benzyl alcohol (prepared according to the method described in Gould, A. E.; Adams, R. D. Design and Optimization of Potent and Orally Bioavailable Tetrahydronaphthalene Raf Inhibitors. J. Med. Chem. 2011, 54, 1836 - 1846!) (5.12 g, 24.75 mmol), and EDC·HCl (11.93 g, 62.25 mmol) into a 1 L round-bottom flask. Subsequently, add 375 mL of dry dichloromethane solution, and continue to add DMAP (7.6 g, 62.25 mmol) under stirring. React at room temperature for 6 hours. After stopping the reaction, slowly add saturated sodium bicarbonate solution (240 mL) to quench the reaction. Separate the organic phase, and extract the aqueous phase with dichloromethane (100 mL × 3). Combine the organic phases and wash them successively with saturated sodium carbonate solution (240 mL), saturated ammonium chloride solution (240 mL), and saturated brine (240 mL). Dry over anhydrous sodium sulfate, filter, and evaporate to dryness. Dissolve the obtained solid completely in about 20 mL of dichloromethane, then add 60 mL of methanol solution. Precipitate the solid, filter after standing for 15 minutes, and wash with 10 mL of methanol solution to obtain the compound shown in the structure of formula Ⅳa, with a yield of 82%.

[0053] 1 1H NMR (500 MHz, CDCl3, ppm): δ 8.96 (s, 3H), 8.54 (s, 3H), 8.49 (s, 3H), 8.05 (s, 3H), 5.58 (s, 6H);

[0054] 13 13C-NMR (125 MHz, CDCl3, ppm): δ 164.0, 148.6, 138.9, 135.4, 132.9 (q, J = 34.4 Hz, C-CF3), 130.8, 130.7 (q, J = 3.5 Hz, C-C-CF3), 126.3, 122.6 (q, J = 273.1 Hz, CF3), 120.9 (q, J = 3.9 Hz, C-C-CF3), 65.4.

[0055] As can be seen from the above, the structure of the above compound is correct and it is the compound shown in formula Ⅳa.

[0056] Example 2: Preparation of the ester-linked arm compound (R is hydrogen) shown in the general formula of formula Ⅲa

[0057] The reaction formula is as follows:

[0058]

[0059] In a 1 L round-bottom flask, add compound Ⅳa (5.73 g, 7 mmol) and 500 mL of tetrahydrofuran solution. Slowly add a concentrated hydrochloric acid solution (50 mL) of stannous chloride (18.9 g, 84 mmol) dropwise to the system and react at room temperature for 10 hours. After stopping the reaction, adjust the reaction system to pH > 10 with 30% aqueous sodium hydroxide solution, separate the organic phase, extract the aqueous phase with ethyl acetate (200 mL × 3), combine the organic phases, wash with saturated brine (240 mL), dry over anhydrous sodium sulfate, filter and concentrate by rotary evaporation, mix with silica gel, and perform column chromatography with petroleum ether:ethyl acetate = 2:1 to obtain the compound shown in the structure of formula Ⅲa with a yield of 87%.

[0060] 1 H NMR (500 MHz, DMSO-d6, ppm): δ 8.72 (s, 3H), 6.88 - 6.86 (m, 6H), 6.82 (s, 3H), 5.68 (s, 6H), 5.35 (s, 6H);

[0061] 13 C-NMR (125 MHz, DMSO-d6, ppm): δ 164.4, 150.2, 138.1, 134.2, 131.5, 130.5 (q, J = 31.5 Hz, C-CF3), 124.8 (q, J = 273.1 Hz, CF3), 116.8, 111.5 (q, J = 3.7 Hz, C-C-CF3), 109.8 (q, J = 3.7 Hz, C-C-CF3), 67.1;

[0062] HRMS (ESI): m / z calcd: 730.1594 [M + H] + ; Found: 730.1584 [M + H] + .

[0063] As can be seen from the above, the structure of the above compound is correct and it is the compound shown in formula Ⅲa.

[0064] Example 3. Preparation of the ester group-linked arm compound shown in the general formula of formula Ⅱa (R is hydrogen)

[0065] The reaction formula is as follows:

[0066]

[0067] In a 100 mL round-bottom flask, compound Ⅲa (1.46 g, 2 mmol) and 50 mL of dry dichloromethane solution were added. Under stirring conditions, 1,1'-thiocarbonyldiimidazole (2.14 g, 12 mmol) was added, and the system was reacted at room temperature for 24 hours. After rotary evaporation, the sample was mixed with silica gel, and column chromatography was carried out with petroleum ether:dichloromethane = 2:1 to obtain the compound shown in the structure of formula Ⅱa with a yield of 62%.

[0068] 1 H NMR (500 MHz, CD3CN, ppm): δ 8.73 (s, 3H), 7.88 (s, 3H), 7.87 (s, 6H), 5.49 (s, 6H);

[0069] 13 C-NMR (125 MHz, CD3CN, ppm): δ 163.7, 139.2, 135.5, 133.9, 131.4, 130.7, 130.6 (q, J = 32.6 Hz, C-CF 3) , 129.4, 123.7 (q, J = 4.1 Hz, C-C-CF3), 123.1 (q, J = 273.1 Hz, CF3), 122.5 (q, J = 4.0 Hz, C-C-CF3), 65.4;

[0070] HRMS (ESI): m / z calcd: 856.0286 [M+H] + ; Found: 856.0263 [M+H] + .

[0071] As can be seen from the above, the structure of the above compound is correct and it is the compound shown in formula Ⅱa.

[0072] Example 4. Preparation of the ester group-linked symmetric molecular cage compound shown in the general formula of structure Ⅰa (R is hydrogen). The reaction formula is as follows:

[0073]

[0074] The specific preparation method is as follows:

[0075] A magnetic stirrer, the fragment derivatives shown in Ⅱa (428 mg, 0.5 mmol) and Ⅲa (365 mg, 0.5 mmol) were added to a clean round-bottom flask, and 200 mL of pyridine solvent was added. The reaction was carried out at room temperature for 48 hours. The reaction solution changed from a colorless transparent solution to a yellow solution. After the reaction was completed, pyridine was rotary evaporated, the sample was mixed with silica gel, and column chromatography was carried out using petroleum ether:acetone = 7:4 as the eluent to separate 348 mg of the compound shown in the structure of formula Ⅰa with a yield of 44%.

[0076] 11H NMR (500 MHz, CD3CN, ppm): δ 8.69 (s, 6H), 8.63 (s, 6H), 7.85 (s, 6H), 7.74 (s, 6H), 7.58 (s, 6H), 5.36 (s, 12H);

[0077] 13 13C-NMR (125 MHz, CD3CN, ppm): δ 181.5, 164.8, 140.2, 140.1, 138.9, 134.7, 131.3 (q, J = 32.7 Hz, C-CF3), 128.4, 124.5 (q, J = 271.8 Hz, CF3), 122.6 (q, J = 3.6 Hz, C-C-CF3), 121.9 (q, J = 3.5 Hz, C-C-CF3), 66.7;

[0078] HRMS (ESI): m / z calcd: 1585.1769 [M+H] + ; Found: 1585.1779 [M+H] + .

[0079] As can be seen from the above, the structure of the above compound is correct and it is the compound shown in Formula Ia.

[0080] Example 5: Preparation of a phenol-based linker compound (R is hydrogen) represented by the general formula of Structure IVb

[0081] The reaction formula is as follows:

[0082]

[0083] Add 1,3,5-tris(4-hydroxyphenyl)benzene (1.65 g, 15 mmol), potassium carbonate (6.21 g, 45 mmol) and 120 mL of acetone solvent into a 250 mL round-bottom flask. While stirring, slowly add 60 mL of an acetone solution of 3-nitro-5-(trifluoromethyl)benzyl bromide (synthesized according to Gould, A.E.; Adams, R.Design and Optimization of Potent and Orally Bioavailable Tetrahydronaphthalene Raf Inhibitors. J. Med. Chem. 2011, 54, 1836 - 1846) (9.36 g, 33 mmol) dropwise to the system. After the addition is complete, stir and react at room temperature for 72 hours. Rotate to dry the reaction solution, extract with dichloromethane (100 mL × 3), combine the organic phases, dry over anhydrous sodium sulfate, filter and rotate to dry, then recrystallize with dichloromethane, and filter with suction to obtain 3.8 g of the compound shown in Structure IVb, with a yield of 80%.

[0084] 1 H-NMR (500 MHz, DMSO, ppm): δ 8.64 (s, 3H), 8.48 (s, 3H), 8.35 (s, 3H), 7.83 - 7.85 (m, 6H), 7.77 (s, 3H), 7.19 (d, J = 3 Hz, 6H), 5.44 (s, 6H);

[0085] 13 C-NMR (125 MHz, DMSO, ppm): δ 157.5, 148.2, 141.4, 140.8, 133.3, 130.2 (q, J = 32.4 Hz, C-C-CF3), 130.0 (q, J = 3.9 Hz, C-C-CF3), 128.3, 125.8, 124.0, 122.9 (q, J = 271.5 Hz, CF3), 119.73 (q, J = 3.9 Hz, C-C-CF3), 115.2, 67.3;

[0086] HRMS (ESI): m / z calcd: 964.1911 [M+H] + ; Found: 964.1903 [M+H] + .

[0087] As can be seen from the above, the structure of the above compound is correct and it is the compound shown in Formula Ⅳa.

[0088] Example 6. Preparation of a phenol-based linker compound (R is hydrogen) shown by the general formula of Structure Ⅲb

[0089] The reaction formula is as follows:

[0090]

[0091] Weigh compound Ⅳb (1.9 g, 2 mmol), palladium on carbon (200 mg, 10%) and 150 mL of ethyl acetate in a 250 mL round-bottom flask. After bubbling argon for 10 minutes, hydrogen is introduced into it and the reaction is carried out at room temperature for 48 hours. After stopping the reaction, it is filtered and concentrated by rotary evaporation. The sample is mixed with silica gel, and column chromatography is carried out with petroleum ether:dichloromethane = 4:1 to obtain 1.67 g of the compound shown by Structure Ⅲb, with a yield of 96%.

[0092] 1 H-NMR (500 MHz, DMSO, ppm): δ 7.78 - 7.80 (m, 6H), 7.74 (s, 3H), 7.10 - 7.12 (d, J = 8.6 Hz, 6H), 6.88 - 6.90 (d, J = 11.06 Hz, 6H), 6.80 (s, 3H), 5.67 (s, 6H), 5.12 (s, 6H);

[0093] 13 13C-NMR (125 MHz, DMSO, ppm): δ 157.9, 149.6, 140.9, 139.1, 132.9, 129.8 (q, J = 32.4 Hz, C-C-CF3), 128.2, 124.4 (q, J = 271.5 Hz, CF3), 122.7, 115.6, 115.1, 110.2 (q, J = 3.5 Hz, C-C-CF3), 108.9 (q, J = 3.7 Hz, C-C-CF3), 68.7;

[0094] HRMS (ESI): m / z calcd: 874.2686 [M+H] + ; Found: 874.2682 [M+H] + .

[0095] As can be seen from the above, the structure of the above compound is correct and it is the compound shown in Formula IIIb.

[0096] Example 7: Preparation of a phenol-based linker compound (R is hydrogen) shown by the general formula of Structure IIb

[0097] The reaction formula is as follows:

[0098]

[0099] To a solution of Compound IIIb (1.3 g, 1.5 mmol) in dichloromethane (100 mL) in a 250 mL round-bottom flask was added 1,1'-thiocarbonyldiimidazole (1.6 g, 9 mmol). The system was stirred at room temperature for 24 hours. After stopping the reaction, the solution was evaporated to dryness, and the residue was triturated with silica gel. Column chromatography was performed using petroleum ether:acetone = 3:1 to obtain 1.1 g of the compound shown in Structure IIb, with a yield of 74%.

[0100] 1 1H-NMR (500 MHz, DMSO, ppm): δ 7.64 - 7.67 (m, 9H), 7.62 (s, 3H), 7.52 (s, 3H), 7.44 (s, 3H), 7.07 (d, J = 8.4 Hz, 6H), 5.15 (s, 6H);

[0101] 1313C-NMR(125MHz, DMSO, ppm): δ 157.8, 141.7, 140.3, 134.7, 132.9, 132.6 (q, J = 33.4 Hz, C-CF3), 128.6, 127.4, 124.1 (q, J = 271.3 Hz, CF3), 122.3 (q, J = 3.9 Hz, C-C-CF3), 122.0 (q, J = 3.9 Hz, C-C-CF3), 115.1, 68.4;

[0102] HRMS(ESI): m / z calcd: 1000.1378 [M+H] + ; Found: 1000.1371 [M+H] + .

[0103] As can be seen from the above, the structure of the above compound is correct and it is the compound shown in Formula IIb.

[0104] Example 8: Preparation of a phenolic-bridged extended molecular cage compound (R is hydrogen) represented by the general formula of Structure Ib

[0105] The reaction formula is as follows:

[0106]

[0107] The specific preparation method is as follows:

[0108] Add a magnetic stir bar, the fragment derivatives shown in IIb (500 mg, 0.5 mmol) and IIIb (437 mg, 0.5 mmol) to a clean round-bottom flask, and add 200 mL of pyridine solvent. React at room temperature for 48 hours. The reaction solution changes from a colorless transparent solution to a yellow solution. After the reaction is completed, rotary evaporate the pyridine, mix with silica gel, and perform column chromatography separation using petroleum ether:acetone = 1:2 as the eluent to obtain a solid. Add chloroform solution to completely dissolve the solid and then let it stand to precipitate a white solid. Filter by suction to obtain 403 mg of the compound shown in Structure Ib, with a yield of 43%.

[0109] 1 1H-NMR(500 MHz, CD3CN, ppm): δ 8.67 (s, 6H), 7.74 (s, 6H), 7.66 (s, 6H), 7.58 (s, 6H), 7.48 (m, 18H), 6.96 (d, 12H), 5.10 (s, 12H);

[0110] 1313C-NMR (125 MHz, CD3CN, ppm): δ 181.3, 158.5, 141.8, 140.6, 140.0, 134.3, 131.2 (q, J = 32.4 Hz, C-CF3), 128.9, 126.9, 124.7 (q, J = 273.3 Hz, CF3), 123.8, 121.3 (q, J = 3.2 Hz, C-C-CF3), 120.9 (q, J = 3.3 Hz, C-C-CF3), 115.7, 68.8;

[0111] HRMS (ESI): m / z calcd: 1895.3811 [M+Na] + ; Found: 1895.3817 [M+Na] + .

[0112] As can be seen from the above, the structure of the above compound is correct and it is the compound shown in Formula Ib.

[0113] Example 9, Anion Recognition Performance

[0114] The symmetric molecular cage prepared in the present invention is a novel anion detection reagent and has good recognition effects on various anions, such as chloride ions, carboxylate ions, sulfonate ions, etc.

[0115] Nuclear magnetic titration is an important method for molecular recognition. By keeping the concentration of the host constant and gradually increasing the concentration of the guest, the trend of the nuclear magnetic shift change of thiourea hydrogen is observed to judge the recognition ability of the host for the guest. The solvents selected for nuclear magnetic titration are: deuterated chloroform, deuterated acetone, deuterated DMSO, deuterated acetonitrile, etc., and deuterated acetonitrile is preferred. The specific operation is as follows: The first step is to prepare a deuterated acetonitrile solution A (1.1 mL) of the molecule shown in Formula I with a concentration of 1 mM or 2 mM for standby; the second step is to prepare 600 μL of a guest solution B with a concentration of 20 mM or 40 mM using this solution A for standby; the third step is to add 500 μL of solution A to a clean nuclear magnetic tube, collect a set of 1 1H NMR data, record the relevant chemical shifts, add a certain volume of guest solution B to the nuclear magnetic tube, mix evenly, then collect a set of data again, record the relevant chemical shifts, and repeat the above operations to obtain a series of data, as shown in Table 1.

[0116] Table 1 Anion Titration Experiment of the Compound Shown in Formula I

[0117]

[0118]

[0119] From Figure 1It can be seen from the NMR titration diagram (titration of Formula Ia with chloride ions) shown that during the recognition experiment, as the chloride ion concentration increases, the thiourea hydrogen of Formula Ia gradually shifts to a lower field, with a shift of nearly 3.5 ppm. Similar displacement phenomena of thiourea hydrogen occur when various other anions are used to titrate Formula Ia and Formula Ib. After the thiourea hydrogen in the molecular cage compound represented by Structural General Formula I binds to an anion, it gradually shifts to a lower field due to the action of hydrogen bonds. Its binding constant for the trianion is relatively large, and the binding constants are shown in Table 1.

[0120]

[0121] Table 1 Anion recognition performance of the compound represented by Formula I

[0122]

Claims

1. The compound shown in Formula IV Wherein, R is -H; X is selected from any one of the following groups: -COO-, - p -PhO- and - p -Ph-N(CH3)-.

2. The preparation method of the compound shown in Formula IV of Claim 1, comprising the following steps: Reacting the compound shown in Formula V with 3-nitro-5-trifluoromethylbenzyl alcohol or 3-nitro-5-trifluoromethylbenzyl bromide in the presence of a base and a condensing agent to obtain the product; In the formula, R is -H; X is selected from any one of the following groups: -COO-, - p -PhO- and - p -Ph-N(CH3)-.

3. The preparation method according to claim 2, characterized in that: The base is selected from any one of triethylamine, 4-dimethylaminopyridine, diisopropylethylamine, pyridine, potassium carbonate and sodium carbonate; The condensing agent is selected from any one of dicyclohexylcarbodiimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, 2-(7-azabenzotriazol)-N,N,N',N'-tetramethyluronium hexafluorophosphate and benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate; The solvent for the reaction is at least one of tetrahydrofuran, dichloromethane, ethyl acetate, acetone, acetonitrile and methanol; The temperature of the reaction is -20 to 80 °C, and the time is 3 to 96 h; The molar ratio of the compound shown in Formula V to the 3-nitro-5-trifluoromethylbenzyl alcohol or the 3-nitro-5-trifluoromethylbenzyl bromide is 1:3 to 6.

4. The compound shown in Formula III In the formula, R is -H; X is selected from any one of the following groups: -COO-, - p -PhO- and - p -Ph-N(CH3)-.

5. The preparation method of the compound shown in Formula III of Claim 4, comprising the following steps: Reacting the compound shown in Formula IV by a reduction reaction in the presence of a reducing agent to obtain the product; The reducing agent is stannous chloride or palladium on carbon; The solvent for the reduction reaction is any one of tetrahydrofuran, dichloromethane, ethyl acetate and acetonitrile; The molar ratio of the compound shown in Formula IV to the reducing agent is 1:3 to 12; The temperature of the reduction reaction is -20 to 80 °C, and the time is 3 to 96 h.

6. The compound shown in Formula II In the formula, R is -H; X is selected from any one of the following groups: -COO-, - p -PhO- and - p -Ph-N(CH3)-.

7. The preparation method of the compound shown in Formula II of Claim 6, comprising the following steps: Reacting the compound shown in Formula III with 1,1'-thiocarbonyldiimidazole to obtain the product; The solvent for the reaction is any one of tetrahydrofuran, acetonitrile, dichloromethane, N,N-dimethylformamide and dimethyl sulfoxide; The molar ratio of the compound shown in Formula III to the 1,1'-thiocarbonyldiimidazole is 1:3 to 12; The temperature of the reaction is -20 to 80 °C, and the time is 3 to 96 h.

8. The symmetric molecular cage shown in Formula I In the formula, R is -H; X is selected from any one of the following groups: -COO-, - p -PhO- and - p -Ph-N(CH3)-.

9. The preparation method of the symmetric molecular cage shown in Formula I of Claim 8, comprising the following steps: Reacting the compound shown in Formula II with the compound shown in Formula III in the presence of a base to obtain the product; In the formula, R is -H; X is selected from any one of the following groups: -COO-, - p -PhO-, and - p -Ph-N(CH3)-.

10. The preparation method according to claim 9, characterized in that: The base is any one of triethylamine, DMAP, DIPEA and pyridine; The solvent for the reaction is any one of N,N-dimethylformamide, dimethyl sulfoxide, pyridine and acetonitrile; The molar ratio of the compound shown in Formula II, the compound shown in Formula III to the base is 1:1:3 to 12; The temperature of the reaction is -20 to 80 °C, and the time is 3 to 72 h.

11. The application of the symmetric molecular cage shown in Formula I of Claim 8 in anion recognition; The anions include inorganic anions and organic anions; The inorganic anions are fluoride ion, chloride ion, bromide ion or iodide ion; The organic anions are monocarboxylate ion, monosulfonate ion, tricarboxylate ion, trisulfonate ion or phosphate ion.

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