Barbituric acid macrocycle and preparation method and application thereof

Abstract

The application discloses a barbituric acid macrocycle compound and a preparation method and application thereof. The structural formula of the barbituric acid macrocycle compound is shown as formula I, formula II, formula III or formula IV. The barbituric acid macrocycle compound and an assembly thereof can be used for separating organic small molecules. When the barbituric acid macrocycle compound is applied, the barbituric acid macrocycle compound or the assembly thereof is filled as a filler in a filter column, and the separation of the organic small molecules is realized through a column chromatography method. In the application, inexpensive and readily available raw materials are selected, starting from several inexpensive and readily available reagents such as substituted malonyl chloride, substituted ketone compounds, 1,3-dibenzyl bromide and substituted barbituric acid. Through simple nucleophilic substitution reaction and dehydration condensation reaction, the barbituric acid macrocycle compound with multiple substitutions can be quickly prepared, and can be applied to the separation of dyes, and has good practicability and application prospect.

Description

Technical Field

[0001] This invention relates to a barbituric acid macrocyclic compound, its preparation method and application, and belongs to the field of organic chemistry. Background Technology

[0002] The carbonyl group is one of the most important functional groups in chemistry and biology, due to its unique reactivity, spectral characteristics, and role as a hydrogen bond acceptor in supramolecular and biological systems. Bürgi and Dunitz first proposed the interaction between the lone pair electrons of the nucleophile and the carbonyl group (n→π* interaction) for mapping the reaction coordinates of carbonyl nucleophilic addition (Bürgi, HB, Dunitz, JDJAm. Chem. Soc. 1973, 95, 5065-5067.). This non-covalent interaction has recently attracted increasing attention across various disciplines. Since Raines' group proposed the contribution of n→π* interactions related to Bürgi-Dunitz orbitals to the stability of collagen conformation (Raines, RTT J Am. Chem. Soc. 2001, 123, 777-778.), more and more researchers have devoted themselves to revealing the importance of n→π* interactions in proteins and peptides (Raines, RTT Nat. Chem. Bio. 2010, 6, 615-620.). On the other hand, studies on controlling conformation through molecular design by manipulating intramolecular n→π* interactions (Wennemers, HJ Am. Chem. Soc. 2006, 128, 14697-14703.) and regulating supramolecular assembly (Castellano, RK J Am. Chem. Soc. 2021, 143, 12688-12698.) also have great application prospects.

[0003] Currently, n→π* interactions as non-covalent driving forces are limited to intramolecular systems. In principle, intermolecular n→π* interactions can generate fascinating supramolecular systems, but due to the extremely low energy of individual interactions (~0.3-0.7 kcal / mol) (Raines, RTAcc. Chem. Res. 2017, 50, 1838-1846.), they remain largely unexplored. Therefore, fine molecular design that combines multiple carbonyl groups and cooperating carbonyl groups into an approximate space to amplify binding energies shows promise and has potential applications in anion recognition, self-assembly, catalysis, and separation. Summary of the Invention

[0004] The purpose of this invention is to provide a barbituric acid macrocyclic compound containing multiple substitutions, which can be used for the separation of small organic molecules such as organic dyes.

[0005] The structural formulas of the barbituric acid macrocyclic compounds provided by the present invention are shown in Formula I, Formula II, Formula III or Formula IV, wherein the compounds shown in Formula I and Formula II are calix[2]arene[2]barbituric acid macrocyclic compounds, the compounds shown in Formula III are calix[3]arene[3]barbituric acid macrocyclic compounds, and the compounds shown in Formula IV are calix[4]arene[4]barbituric acid macrocyclic compounds.

[0006]

[0007] In each formula, R 1 R 2 R 3 Independently selected from any one of the following groups:

[0008] -H, -C1 to C6 alkyl, -F, -Cl, -Br, -I, benzyl, substituted benzyl;

[0009] The substituents on the substituted benzyl group can be -H, -C1 to C6 alkyl, -F, -Cl, -Br, or -I.

[0010] This invention provides methods for preparing various barbituric acid macrocyclic compounds;

[0011] The preparation method of the barbituric acid macrocyclic compound shown in Formula I includes the following steps:

[0012] The compound shown in Formula V and the compound shown in Formula VI undergo a nucleophilic substitution reaction to give the compound shown in Formula I.

[0013]

[0014] In Equation VI, R 1 R 2 R 3 The definition is the same as that of Equation I.

[0015] The organic solvent used in the nucleophilic substitution reaction is at least one of chloroform, carbon tetrachloride, and dichloroethane;

[0016] The nucleophilic substitution reaction is carried out at a temperature of 60–80 °C for 10–15 hours.

[0017] The ratio of the compound shown in Formula V and the compound shown in Formula VI to the organic solvent is 0.2–3.0 mmol: 0.4–9.0 mmol: 15–150 mL;

[0018] The compound shown in Formula V can be prepared using existing methods.

[0019] The preparation method of the barbituric acid macrocyclic compound shown in Formula II includes the following steps:

[0020] The compound shown in formula Ia and the compound shown in formula VII undergo a condensation reaction to obtain the compound shown in formula II;

[0021]

[0022] In equation VII, R 1 R 2 R 3 Definition of the same as formula II

[0023] The organic solvent used in the condensation reaction is at least one of methanol, ethanol, propanol and isopropanol;

[0024] The ratio of the compound shown in Formula Ia and Formula VII to the organic solvent is 0.1–1.0 mmol: 0.3–3.0 mmol: 10–100 mL;

[0025] The condensation reaction is carried out at a temperature of 70–90°C for 8–10 hours.

[0026] The preparation method of the barbituric acid macrocyclic compound represented by Formula I, Formula III, or Formula IV includes the following steps:

[0027] In the presence of a base, the compound shown in Formula VIII and the compound shown in Formula IX undergo a nucleophilic substitution reaction to give the compounds shown in Formula I, Formula III and / or Formula IV.

[0028]

[0029] In equation VIII, R 1 R 2 R 3 The definition is the same as that of Equation I, Equation III, or Equation IV.

[0030] The organic solvent used in the nucleophilic substitution reaction is N,N-dimethylformamide;

[0031] The alkali is sodium hydride and / or potassium hydride;

[0032] The compounds shown in Formula VIII and Formula IX, and the ratio of the base to the organic solvent are 1.0 mmol: 1.0 mmol: 2.0 mmol to 2.5 mmol: 200 mL;

[0033] The nucleophilic substitution reaction is carried out at a temperature of 70–90 °C for 20–24 hours.

[0034] The barbituric acid macrocyclic compounds and their assemblies provided by this invention can be used to separate small organic molecules, such as organic dyes, specifically MY (methyl yellow) and PB (pyronin B).

[0035] When using the barbituric acid macrocyclic compound of the present invention, the barbituric acid macrocyclic compound or its assembly is used as a packing material in a filter column, and the small organic molecules are separated by column chromatography.

[0036] This invention uses inexpensive and readily available raw materials, starting with several inexpensive and readily available reagents such as substituted malonyl chloride, substituted ketone compounds, 1,3-dibenzyl bromide, and substituted barbituric acid. Through simple nucleophilic substitution reactions and dehydration condensation reactions, polysubstituted barbituric acid macrocyclic compounds can be rapidly prepared and applied to the separation of dyes, showing great practicality and application prospects. Attached Figure Description

[0037] Figure 1 This is a schematic diagram of the assembly formed by the macrocycle of calix[2]aromatic[2]barbituric acid as shown in formula Ia.

[0038] Figure 2 This is a schematic diagram of the assembly formed by the macrocycle of calix[2]aromatic[2]barbituric acid shown in Formula Ia as a single crystal column for separating MY and PB.

[0039] Figure 3 This is a schematic diagram of a glass column used as packing material to separate MY and PB, which is formed by the assembly of the calix[2]aromatic[2]barbituric acid macrocycle shown in Formula Ia. Detailed Implementation

[0040] Unless otherwise specified, the experimental methods used in the following examples are conventional methods.

[0041] Unless otherwise specified, all materials and reagents used in the following examples are commercially available.

[0042] The compounds represented by formula V used in the following examples were prepared according to the following method:

[0043] The reaction equation is as follows:

[0044]

[0045] A magnetic stir bar, compound X (1 g, 6.4 mmol), sodium hydride (0.77 g, 19.2 mmol), and 180 mL of dry tetrahydrofuran were added to a clean two-necked flask. The mixture was reacted at 70 °C for 1 h, then cooled to room temperature. Compound IX (1.68 g, 6.4 mmol) was then dissolved in 50 mL of dry tetrahydrofuran, and the tetrahydrofuran solution of compound IX was added to the tetrahydrofuran solution of compound X. The reaction was continued at 70 °C for 18 h, then the reaction was stopped. The mixture was cooled to room temperature, and 5 mL of water was added to quench the reaction. The solvent in the system was evaporated to dryness, and the mixture was extracted with ethyl acetate (100 mL × 3). The organic phases were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The mixture was filtered and evaporated to dryness, then separated by column chromatography (silica gel 100–200 mesh, eluent: ethyl acetate ~ ethyl acetate / methanol = 40:1) to give 528 mg of the white solid compound XI, with a yield of 32%.

[0046] A magnetic flask was added to a clean two-necked flask containing the compound of formula XI (0.26 g, 0.55 mmol), 10 mL of an aqueous solution of 20% diethanolamine (pH = 3), and 10 mL of methanol. The mixture was heated under reflux overnight. The reaction was cooled to room temperature, filtered to obtain a solid, and washed with water to give 140 mg of the white solid compound of formula V, with a yield of 78%.

[0047] 1 H NMR (DMSO, 300MHz) δ7.30 (s, 2H), 7.16 (t, J = 7.4Hz, 2H), 7.0 (d, J = 6.9Hz, 4H), 6.46 (br s, 4H), 4.6 (v br m, 4H), 3.8 (v br m, 4H). 13 C NMR (75MHz, DMSO) δ158.0,141.8,127.5,124.9,123.3,42.4.

[0048] Example 1: Preparation of macrocyclic (R) shown in formula Ia 1 -H, R 2 -H, R 3 (for -H)

[0049] The reaction equation is as follows:

[0050]

[0051] The specific preparation method is as follows:

[0052] A magnetic flask was added to a clean two-necked flask containing the compound of formula V (200 mg, 0.6 mmol), malonyl chloride of formula VIa (120 μL, 1.2 mmol), and 30 mL of chloroform. The reaction was carried out at 70 °C for 12 h, and then the reaction was stopped. The solvent in the system was evaporated, and the mixture was separated by column chromatography (silica gel 100-200 mesh, eluent: dichloromethane / methanol = 100:1-80:1) to obtain 180 mg of the white solid compound of formula Ia, with a yield of 66%.

[0053] 1 H NMR (CD2Cl2, 500MHz) δ7.65 (s, 2H), 7.38 (d, J = 7.5Hz, 4H), 7.23 (t, J = 7.4Hz, 2H), 5.02 (s, 8H), 3.65 (s, 4H);

[0054] 13 C NMR (CD2Cl2, 125MHz) δ164.7,151.8,136.9,130.2,130.0,128.9,45.0,40.0;

[0055] HRMS (APCI) - )calc.for[MH] - (C 24 H 19 N4O6 - ): 459.13046, found 459.13040.

[0056] As can be seen from the above, the structure of the above compound is correct, and it is the compound shown in formula Ia.

[0057] Example 2: Preparation of macrocyclic (R) shown in formula Ib 1 -H, R 2 For -CH3, R 3 (for -H)

[0058] The reaction equation is as follows:

[0059]

[0060] The specific preparation method is as follows:

[0061] A magnetic ball, compound V (162 mg, 0.5 mmol), 2-methylmalonyl chloride (154 mg, 1 mmol), and 30 mL of chloroform were added to a clean two-necked flask. The reaction was carried out at 70 °C for 12 h, and then the reaction was stopped. The solvent in the system was evaporated, and the mixture was separated by column chromatography (silica gel 100-200 mesh, eluent: dichloromethane / methanol = 100:-40:1) to obtain 205 mg of the white solid compound shown in formula Ib, with a yield of 84%.

[0062] 1 H NMR (CDCl3, 500MHz) δ7.64 (d, 2H), 7.39 (d, J = 7.3Hz, 4H), 7.55 (t, J = 7.3Hz, 18H), 5.07-5.01 (m, 8H), 3.52-3.43 (m, 2H), 1.66-1.62 (m, 6H);

[0063] 13 C NMR (CDCl3, 125MHz) δ168.4,150.78,150.75,136.19,136.14,129.72,129.68,128.79,128.78,44.80,44.74,43.97,14.60,14.34;

[0064] HRMS (APCI) + calc.for[M+H] + (C 26 H 25 N4O6 + ): 489.17741, found 489.17670.

[0065] As can be seen from the above, the structure of the above compound is correct, and it is the compound shown in formula Ib.

[0066] Example 3: Preparation of macrocyclic (R) represented by general formula Ic 1 -H, R 2 For -CH2CH3, R 3 (for -H)

[0067] The reaction equation is as follows:

[0068]

[0069] The specific preparation method is as follows:

[0070] A magnetic flask was added to a clean two-necked flask containing the compound of formula V (162 mg, 0.5 mmol), the compound of formula VIc (254 mg, 1.5 mmol), 2-ethylmalonyl chloride, and 30 mL of chloroform. The reaction was carried out at 70 °C for 12 h, and then the reaction was stopped. The solvent in the system was evaporated, and the mixture was separated by column chromatography (100-200 mesh silica gel, eluent: dichloromethane / methanol = 180:1) to obtain 189 mg of the white solid compound of formula Ic, with a yield of 73%.

[0071] 1H NMR(CD2Cl2,500MHz)δ7.49(s,2H),7.37-7.33(m,4H),7.25-7.22(m,2H),5 .08-4.95(m,8H),3.49-3.43(m,2H),2.19-2.11(m,4H),0.88-0.79(m,6H);

[0072] 13 C NMR (CD2Cl2, 125MHz) δ168.6,151.53,151.43,137.09,137.02,129.7,129.2,128. 92,128.88,128.5,127.4,50.55,50.51,45.07,45.03,25.33,25.25,10.53,10.48;

[0073] HRMS (APCI) + calc.for[M+H] + (C 28 H 29 N4O6 + ): 517.20871, found 517.20795.

[0074] As can be seen from the above, the structure of the above compound is correct, and it is the compound shown in formula Ic.

[0075] Example 4: Preparation of macrocyclic (R) shown in Formula II 1 -H, R 2 For -Ph, R 3 (for -H)

[0076] The reaction equation is as follows:

[0077]

[0078] The specific preparation method is as follows:

[0079] A magnetic flask was added to a clean two-necked flask. The compound shown in Formula Ia (46 mg, 0.1 mmol) was dissolved in 10 mL of ethanol. Benzaldehyde (31 μL, 0.3 mmol) shown in Formula VIIa was added, along with ten drops of glacial acetic acid. The mixture was refluxed for 9 h. After the reaction was complete, the mixture was cooled to room temperature, and water was added. A large amount of solid precipitated out. The solid was obtained by filtration and recrystallized from the solid using ethanol to give 67 mg of the yellow solid compound shown in Formula IIa, with a yield of 100%.

[0080] 1H NMR(CD2Cl2,500MHz)δ8.44(d,J=8.8Hz,2H),7.88(t,J=6.5Hz,4H),7.61(s,2H), 7.43(t,J=6.7Hz,2H),7.37-7.32(m,8H),7.21-7.13(m,2H),5.05(d,13.2Hz,8H);

[0081] 13 C NMR (CD2Cl2, 125MHz) δ161.1,159.0,158.7,150.2,136.1,136.09,136.06,136.0,132.5,132.1,131.9,128.9,127.4,127.3,116.9,44.5,43.8;

[0082] HRMS (APCI) + calc.for[M+H] + (C 38 H 29 N4O6 + ): 637.20871, found 637.20840.

[0083] As can be seen from the above, the structure of the above compound is correct, and it is the compound shown in formula IIa.

[0084] Example 5: Preparation of macrocyclic compounds (R) as shown in formulas I, III, and IV 1 R 2 For -CH3, R 3 (for -H)

[0085] The reaction equation is as follows:

[0086]

[0087] The specific preparation method is as follows:

[0088] The compound shown in Formula VIIIa, dimethyl-substituted barbituric acid (156 mg, 1 mmol), and sodium hydride (88 mg, 2.2 mmol) were dissolved in 200 mL of dry DMF and reacted at 0 °C for 1 h. Then, the compound shown in Formula IX, 1,3-dibenzyl bromide (261 mg, 1 mmol), was added, and the reaction was heated to 80 °C for 24 h. After the reaction was completed, the mixture was cooled to room temperature, and the reaction was quenched with water. The solvent in the system was evaporated to dryness, and the mixture was extracted with ethyl acetate (100 mL × 3). The organic phases were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The mixture was filtered and evaporated to dryness, and separated by column chromatography (silica gel 100-200 mesh, eluent: dichloromethane ~ dichloromethane / methanol = 50:1-8:1) to obtain 115 mg of the white solid compound shown in Formula Id (45% yield), 50 mg of the white solid compound shown in Formula IIIa (20% yield), and 31 mg of the white solid compound shown in Formula IVa (12% yield).

[0089] 1 H NMR (CD2Cl2, 500MHz) δ7.33 (d, J = 7.0Hz, 6H), 7.25 (t, J = 8.4Hz, 2H), 5.00 (s, 8H), 1.55 (s, 12H);

[0090] 13 C NMR (CD2Cl2, 125MHz) δ172.7,151.0,137.0,129.2,129.0,127.3,47.8,45.2,25.3;

[0091] HRMS (APCI) + calc.for[M+H] + (C 28 H 29 N4O6 + ): 517.20871, found 517.20850.

[0092] As can be seen from the above, the structure of the above compound is correct, and it is the compound shown in formula Id.

[0093] 1 H NMR(CD2Cl2,500MHz)δ7.36(s,3H),7.24(s,9H),4.96(s,12H),1.52(s,18H);

[0094] 13 C NMR (CD2Cl2, 125MHz) δ172.7,151.2,137.2,129.2,128.8,128.2,48.0,45.4,25.1;

[0095] HRMS (APCI) + calc.for[M+H] + (C 42 H 43 N6O9 + ): 775.30915, found 775.30846.

[0096] As can be seen from the above, the structure of the above compound is correct, and it is the compound shown in formula IIIa.

[0097] 1 H NMR(CD2Cl2,500MHz)δ7.28(s,4H),7.20(s,12H),4.93(s,16H),1.49(s,24H);

[0098] 13 C NMR (CD2Cl2, 125MHz) δ172.8,151.3,137.3,129.1,128.6,128.0,47.9,45.3,25.0;

[0099] HRMS (APCI) + calc.for[M+H] + (C 56 H 57 N8O 12 + ): 1033.40959, found 1033.40976.

[0100] As can be seen from the above, the structure of the above compound is correct, and it is the compound shown in formula IVa.

[0101] Example 6: Preparation of macrocyclic compounds (R) of formulas I and III 1 R 2 For -CH2CH3, R 3 (for -H)

[0102] The reaction equation is as follows:

[0103]

[0104] The specific preparation method is as follows:

[0105] The compound diethyl-substituted barbituric acid (184 mg, 1 mmol) and sodium hydride (88 mg, 2.2 mmol) of formula VIIIb were dissolved in 200 mL of dry DMF. Hydrogen was removed at 0 °C for 1 h. Then, 1,3-dibenzyl bromide (261 mg, 1 mmol) of formula IX was added, and the reaction was heated to 80 °C for 24 h. After the reaction was complete, the mixture was cooled to room temperature, and the reaction was quenched with water. The solvent in the system was evaporated to dryness, and the mixture was extracted with ethyl acetate (100 mL × 3). The organic phases were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The mixture was filtered and evaporated to dryness, and separated by column chromatography (silica gel 100–200 mesh, eluent: petroleum ether / ethyl acetate = 12:1–3:1) to obtain 119 mg of the white solid compound of formula Ie (42% yield) and 59 mg of the white solid compound of formula IIIb (21% yield).

[0106] 1 H NMR (CD2Cl2, 500MHz) δ7.46 (s, 2H), 7.37 (d, J = 7.2Hz, 4H), 7.25 (t, J = 7.5Hz, 2H), 5.07 (s, 8H), 1.90 (dd, J = 7.25Hz, J = 7.0Hz, 8H), 0.50 (s, 12H);

[0107] 13 C NMR (CD2Cl2, 125MHz) δ171.8,151.3,137.4,129.4,128.7,127.3,58.3,45.1,33.5,9.4;

[0108] HRMS (APCI) + calc.for[M+H] + (C 32 H 37 N4O6 + ): 573.27131, found 573.27026.

[0109] As can be seen from the above, the structure of the above compound is correct, and it is the compound shown in formula Ie.

[0110] 1 H NMR (CD2Cl2, 500MHz) 7.36 (s, 3H), 7.25 (s, 9H), 5.02 (s, 12H), 1.96 (dd, J = 7.25Hz, J = 7.4 Hz, 12H), 0.62 (t, J = 7.3Hz, 18H);

[0111] 13C NMR (CD2Cl2, 125MHz) δ171.9,151.2,137.4,129.2,128.6,128.1,58.5,45.3,33.4,9.6;

[0112] HRMS (APCI) + calc.for[M+H] + (C 48 H 55 N6O9 + ): 859.40305,found 859.40179.

[0113] As can be seen from the above, the structure of the above compound is correct, and it is the compound shown in formula IIIb.

[0114] Example 7: Preparation of macrocyclic compounds (R) of formulas I and III 1 R 2 For -Bn, R 3 (for -H)

[0115] The reaction equation is as follows:

[0116]

[0117] The specific preparation method is as follows:

[0118] The compound bisbenzyl-substituted barbituric acid (308 mg, 1 mmol) and sodium hydride (88 mg, 2.2 mmol) of formula VIIIc were dissolved in 200 mL of dry DMF. Hydrogen was removed at 0 °C for 1 h. Then, 1,3-dibenzyl bromide (261 mg, 1 mmol) of formula IX was added, and the reaction was heated to 80 °C for 24 h. After the reaction was complete, the mixture was cooled to room temperature, and the reaction was quenched with water. The solvent in the system was evaporated to dryness, and the mixture was extracted with ethyl acetate (100 mL × 3). The organic phases were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The mixture was filtered and evaporated to dryness, and separated by column chromatography (silica gel 100–200 mesh, eluent: petroleum ether / ethyl acetate = 10:1–8:1) to obtain 138 mg of the white solid compound of formula If (34% yield) and 77 mg of the white solid compound of formula IIIc (19% yield).

[0119] 1 H NMR(CDCl3,500MHz)δ7.02-6.93(m,26H),6.70(s,2H),4.57(s,8H),3.40(s,8H);

[0120] 13C NMR (CDCl3, 125MHz) δ170.3,148.4,135.6,134.5,129.3,128.25,128.18,128.12,127.5,60.1,45.1,44.1;

[0121] HRMS (APCI) + calc.for[M+H] + (C 52 H 45 N4O6 + ): 821.33391, found 821.33344.

[0122] As can be seen from the above, the structure of the above compound is correct, and it is the compound shown in formula If.

[0123] 1 H NMR(CDCl3,500MHz)δ7.01-6.95(m,29H),6.88-6.86(m,15H),6.70(s,8H),6.43(s,4H),4.54(s,16H),3.40(s,16H);

[0124] 13 C NMR (CDCl3, 125MHz) δ170.4,149.1,135.7,134.7,129.4,128.5,128.3,127.4,126.9,60.5,45.4,44.5;

[0125] HRMS (APCI) + calc.for[M+H] + (C 78 H 67 N6O9 + ): 1231.49640, found 1231.49341.

[0126] As can be seen from the above, the structure of the above compound is correct, and it is the compound shown in formula IIIc.

[0127] Example 8: Experiment on the separation of small organic molecules from macrocyclic Ia of calix[2]arene[2]barbituric acid

[0128] The assembly of the calix[2]arene[2]barbituric acid macrocycle (formula Ia) prepared by this invention, such as Figure 1As shown, driven by intermolecular C=O…C=O interactions, adjacent macrocyclic molecules in the compound represented by formula Ia are non-covalently linked, forming an infinite single helix structure. Three such single helices are further entangled together through CH…π interactions between benzene rings, forming an interesting assembly with a diameter of approximately 1.4 nm. This material possesses the ability to separate small organic molecules and represents a novel type of single-crystal column for separating small organic molecules, as well as a novel packing material for separating small organic molecules.

[0129] The filling pattern of the calix[2]aromatic[2]barbituric acid macrocycle shown in Formula Ia in the crystalline state indicates that the nanopores with aromatic rings decorating the inner surface can serve as chromatographic pathways for separating moving agents. This invention selected two colored dye molecules (methyl yellow (MY) and pyranin B (PB)) as analytes and toluene as the eluent. X-ray diffraction confirmed that toluene does not damage the integrity of the single crystal; therefore, rod-shaped single crystals were used as "columns" to separate the mixture of MY and PB.

[0130] The single crystal was vertically fixed on a support, with its bottom slightly immersed in a mixture of MY and PB solutions in toluene. The yellow band (MY) migrated upwards rapidly, while the purple band (PB) migrated more slowly. After 5 minutes, the leading band of yellow MY could be distinguished from the mixed bands, as shown in Figure 2. The left figure is a schematic diagram of single-crystal dye separation, and the right figure is a chromatogram showing the separation of MY from the MY+PB mixture using a single crystal within 5 minutes.

[0131] Furthermore, by packing crystals into a glass column and using column chromatography with toluene as the mobile phase, MY and PB were completely separated, and pure MY was obtained as the first eluting fraction. Figure 3 As shown, the left figure is the initial sample loading diagram of the MY and PB mixture, the middle figure is the elution and separation process diagram of MY and PB, and the right figure is the column diagram of MY after elution and PB.

Claims

1. A barbituric acid macrocyclic compound, the structural formula of which is shown in Formula I; In formula I, R 1 R 2 R 3 Selected independently from -H.

2. A method for preparing the barbituric acid macrocyclic compound shown in Formula I of claim 1, comprising the following steps: The compound shown in Formula V and the compound shown in Formula VI undergo a nucleophilic substitution reaction to give the compound shown in Formula I. In Equation VI, R 1 R 2 R 3 The definition is the same as that of Equation I.

3. The preparation method according to claim 2, characterized in that: The organic solvent used in the nucleophilic substitution reaction is at least one of chloroform, carbon tetrachloride, and dichloroethane; The nucleophilic substitution reaction is carried out at a temperature of 60-80 °C for 10-15 hours. The ratio of the compound shown in Formula V and the compound shown in Formula VI to the organic solvent is 0.2~3.0 mmol: 0.4~9.0 mmol: 15~150 mL.

4. A method for preparing the barbituric acid macrocyclic compound shown in Formula I of claim 1, comprising the following steps: In the presence of a base, the compound shown in formula VIII and the compound shown in formula IX undergo a nucleophilic substitution reaction to give the compound shown in formula I. In equation VIII, R 1 R 2 R 3 The definition is the same as that of Equation I.

5. The preparation method according to claim 4, characterized in that: The organic solvent used in the nucleophilic substitution reaction is N,N-dimethylformamide; The alkali is sodium hydride and / or potassium hydride; The compounds shown in Formula VIII and Formula IX, and the ratio of the base to the organic solvent are 1.0 mmol: 1.0 mmol: 2.0 mmol to 2.5 mmol: 200 mL. The nucleophilic substitution reaction is carried out at a temperature of 70-90 °C for 20-24 hours.

6. The application of the barbituric acid macrocyclic compound and its assembly as described in claim 1 in the separation of small organic molecules; The organic molecule in question is methyl yellow.

7. The application according to claim 6, characterized in that: The barbituric acid macrocyclic compound or its assembly is used as a packing material in a filter column, and the small organic molecules are separated by elution.

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