CN113512044A - Water-soluble benzotriazole supermolecule cup compound, and preparation method and application thereof - Google Patents
Water-soluble benzotriazole supermolecule cup compound, and preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses a water-soluble benzotriazole supermolecule calixarene compound, a preparation method and application thereof, wherein resorcinol and 2, 3-dihydrofuran are used as initial raw materials, and the resorcinol calixarene is obtained through furan ring opening and methylene bridging cyclization, and then electrophilic substitution reaction and SnCl are carried out2Reducing to obtain a tetrachloropropyl octa-amino hydrochloride intermediate, and then constructing a benzotriazole supermolecular cup through similar diazotization reaction. The preparation method has the advantages of simple route and process, easily obtained raw materials, mild reaction conditions, high yield and good repeatability. The benzotriazole group in the benzotriazole water-soluble supermolecule cup structure disclosed by the invention has active proton hydrogen, so that a ring-shaped hydrogen bond array is formed under the assistance of water molecules, and a host has strong host-object recognition performance and shows good host-object complexing behavior in a water phase.
Description
Technical Field
The invention belongs to the field of organic synthesis, and relates to a novel benzotriazole water-soluble supermolecular cup compound, a preparation method thereof and application of molecular recognition performance.
Background
The benzotriazole supermolecule cup refers to a supermolecule cup compound obtained by diazotization reaction of o-phenylenediamine and sodium nitrite on four upper edges, and the synthetic process is shown in figure 1. Compared with the resorcinol calixarene, the structure of the composite material has certain flexibility, and compared with the resorcinol calixarene, the composite material has a relatively high and deep cavity. Therefore, the compound is a novel supermolecule cup compound with weak electron-deficient groups, receives wide attention in the aspect of molecular recognition, and has potential application prospects.
There are two main sites for modification of the supramolecular cup. One was derivatized with o-phenylenediamine at the upper edge of the macrocycle, as shown in FIG. 1, and the other was derivatized at the substituent site of the foot. The technical route for preparing the supermolecule cup with the o-phenylenediamine group is mature, aldehyde and resorcinol are generally adopted as raw materials, Lewis acid is adopted as a catalyst, and then the bi-halogen aromatic ring derivative is adopted for substitution, so that very high yield can be obtained. The technical route for derivatization of the o-phenylenediamine hydrochloride parent is reported in many documents, but no report is found for preparing the supermolecule cup with the upper edge of the benzotriazol group by the diazo-like reaction, as shown in figure 1.
Benzotriazole supermolecule cups can perform conformational transformation in an aqueous phase by virtue of an oxygen bridge bond in a structure to generate a cavity, so as to identify guest molecules, and the aspect has been reported very much. However, it has not been reported that water molecules are introduced into the structure to participate in hydrogen bonding, so that the supermolecular cup can stabilize the 'vase' conformation under the assistance of water.
Disclosure of Invention
In order to solve the problems of the prior art, the invention aims to overcome the defects in the prior art and provide a water-soluble benzotriazole supermolecule cup compound, a preparation method and application thereof. According to the invention, a benzotriazol group with weak electron deficiency is introduced into a supermolecular cup structure, and the host configuration is adjusted through the action of water molecules, so that the host-guest complex can be stabilized by intramolecular hydrogen bonds, and a better molecular recognition performance is shown. It is hoped that the subject will be useful for the transport of drug molecules.
In order to achieve the purpose, the invention adopts the following technical scheme:
a water-soluble benzotriazole supermolecule cup compound has weak electron deficiency effect of benzotriazole group in the compound, and further can generate stable annular hydrogen bond array in a water phase to form a stable host-guest complex in the process of molecular recognition.
Preferably, active hydrogen exists in a benzotriazole group in the structure of the water-soluble benzotriazole supermolecule cup compound, the calixarene presents different four active hydrogen positions, and when all the active hydrogen points to the same position in space, a water molecule in the water phase and the active hydrogen on the upper edge of the main body form an annular hydrogen bond array, so that a main-guest complex in the water phase is stabilized.
Preferably, the water-soluble benzotriazole supermolecule cup compound has the following structural formula:
the invention relates to a preparation method of a water-soluble benzotriazole supermolecule cup compound, which comprises the following synthetic steps:
a. at a low temperature of not higher than 0 ℃, dissolving the octaminohydrochloride precursor in a mixed solvent of acetic acid and water, and slowly adding sodium nitrite into the mixed reaction solution in two batches; then reacting the reaction mixture in an ice-water bath for at least 30 minutes; then removing the ice bath, allowing the reaction mixture to reach room temperature, and stirring for at least 16 hours to react, wherein light orange solid is separated out; after the reaction is finished, adding at least 50mL of water into the product mixed solution, standing, filtering, collecting a filter cake, and then fully washing with a water-ethanol mixed solution with a volume ratio of 1:1 to obtain a light yellow product;
b. dissolving the yellow solid product prepared in the step a in methanol, filtering the yellow solid product to remove insoluble substances after the yellow solid product is dissolved, collecting filtrate, and performing rotary evaporation on the filtrate to obtain a chloropropyl benzotriazole supermolecule cup;
c. in a reaction bottle, dissolving 100mg of chloropropyl benzotriazole supermolecular cup prepared in the step b in at least 10mL of N-methylimidazole, and heating at the temperature of not higher than 110 ℃ overnight under the protection of nitrogen; after the reaction is finished, cooling the product to room temperature, adding acetone into the product, stirring, standing, filtering, washing with acetone, and collecting a solid product; and then carrying out post-treatment on the solid to obtain the benzotriazole supermolecule cup compound.
Preferably, in the step a, 0.5mmol of the octaamino hydrochloride precursor is dissolved in at least 100mL of a mixed solvent of acetic acid and water, wherein the mass fraction of water in the mixed solvent of acetic acid and water is not more than 20%.
Preferably, in the step c, when the post-treatment is carried out, the collected solid product is dissolved in methanol, vacuum concentration under reduced pressure is carried out, filtration is carried out to remove trace solids, and the filtrate is evaporated to obtain solids again; then recovering the solid and suspending the solid in acetone, and heating and refluxing for at least 4h at the temperature of not less than 60 ℃ to obtain a suspension; and then cooling the suspension to room temperature, filtering, fully washing the solid with acetone, and performing vacuum drying to obtain the benzotriazole supermolecule cup compound.
Preferably, the temperature is not higher than 45 ℃ and the vacuum degree is 0.09-0.1 MPa when vacuum concentration is carried out.
Preferably, the post-treatment operation comprises adding a large amount of water, dissolving in methanol, filtering, concentrating under reduced pressure, and measuring the molecular recognition properties of the aqueous solution.
Preferably, in the step c, the benzotriazole supermolecular cup compound obtained is reacted with D2And mixing O, shaking to prepare a clear high-dilution water solution, and storing. Preferably 15.8mg of water-soluble benzotriazole supermolecule cup compound is taken to be placed in at least 10mL of D2And (4) in O.
The application of the water-soluble benzotriazole supermolecule cup compound disclosed by the invention is to perform conformation transformation in a water phase to generate a cavity so as to identify an object molecule, wherein the object molecule is at least one of straight-chain alkane, cycloparaffin, cycloalkanol, cyclic carboxylic acid, cyclic ketone, alkyl alcohol, alkyl carboxylic acid, alkyl glycol, alkyl dicarboxylic acid and ibuprofen medicaments.
Preferably, the water-soluble benzotriazole supermolecule cup compound forms a 1:1 host-guest complex with guest molecules in a water phase in the water phase.
Water molecules are introduced into the benzotriazole supermolecule cup structure to participate in hydrogen bonds, so that the cup supermolecule cup can stabilize the vase conformation under the assistance of water, and the hydrogen bond action is the most common main body self-assembly acting force. The benzotriazol group with weak electron deficiency is introduced into the structure of the supermolecule cup, and the host configuration is adjusted through the action of water molecules, so that the host-guest complex can be stabilized by intramolecular hydrogen bonds, and the good molecular recognition performance is shown.
Compared with the prior art, the invention has the following obvious and prominent substantive characteristics and remarkable advantages:
1. the benzotriazole supermolecule cup compound has a novel structure, embodies the characteristic of active hydrogen, can be used as a donor of a ring-shaped hydrogen bond, and has a potential application prospect in the field of molecular recognition;
2. the synthesis route has simple and convenient process, easily obtained raw materials, mild reaction conditions, high yield and good repeatability, and provides reference for synthesizing calixarene main compound molecules with symmetrical characteristics;
3. the supermolecule cup can form a host-guest complex with various types of guests in the water phase. The existence of active hydrogen on the upper edge of the host can be complemented with water molecules to form annular hydrogen bonds, and the stability of the host-guest complex is further stabilized through the action of the hydrogen bonds.
Drawings
FIG. 1 is a synthesis scheme of a water-soluble benzotriazole supermolecule cup 1.
FIGS. 2 to 9 are nuclear magnetic spectra and high resolution mass spectra of the water-soluble benzotriazole supermolecule cup 1. Wherein, FIG. 2 is the nuclear magnetic hydrogen spectrum of the tetra-chloropropyl octa-amino hydrochloride precursor; FIG. 3 is a nuclear magnetic hydrogen spectrum of a tetrachloropropyl benzotriazole supermolecule cup; FIG. 4 is a tetrachloro propyl benzotriazole supermolecular cup nuclear magnetic carbon spectrum; FIG. 5 is a high-resolution mass spectrum [ M + Na ] of a tetrachloro-propyl benzotriazole supermolecular cup]+(ii) a FIG. 6 shows the water-soluble benzotriazole ultraseparationA sub-cup nuclear magnetic hydrogen spectrum; FIG. 7 is a nuclear magnetic hydrogen spectrum of water-soluble benzotriazole supermolecule cup; FIG. 8 is a water-soluble benzotriazole supermolecule cup high resolution mass spectrum [ M-2Cl ]]2+(ii) a FIG. 9 is a water-soluble benzotriazole supermolecular cup high-resolution mass spectrum [ M-3Cl ]]3+。
FIGS. 10-13 are the hydrogen spectra and object structure diagrams of supramolecular cup 1 complex linear alkane. Wherein, fig. 10 is a nuclear magnetic hydrogen spectrum of linear paraffin identified by water-soluble benzotriazole supermolecular; FIG. 11 is a schematic view of a computational model of water molecules participating in formation of cyclic hydrogen bonds (n-octane guest); FIG. 12 is a nuclear magnetic hydrogen spectrum of linear alkane complexed with host 1, wherein the black star is a free guest and the gray star is complex and the latter two conformations; FIG. 13 is a schematic representation of the complex conformation of water-soluble supramolecular cup 1 and alkane guest of varying lengths.
FIGS. 14-15 are the hydrogen spectra of supramolecular cup 1 complexed cycloalkane and its substitutes. Wherein, FIG. 14 is the nuclear magnetic hydrogen spectrum of the complexation of cycloalkane with host 1, and the black star is the free guest; the grey star is the link and the object; FIG. 15 is a nuclear magnetic hydrogen spectrum of a cycloalkane substituent complexed with a subject 1.
FIGS. 16-17 are diagrams of supramolecular cup 1 complex alkyl alcohol, alkyl carboxylic acid hydrogen spectra and guest conformation. FIG. 16 is a nuclear magnetic hydrogen spectrum of alkyl carboxylic acid complexed with host 1, with the free guest being a black star; figure 17 is a schematic representation of the conformation of an alkyl alcohol and an alkyl carboxylic acid in host 1.
FIGS. 18-19 are graphs of supramolecular cup 1 complex alkyldiol, hydrogen dicarboxylates, and guest conformation. FIG. 18 is a nuclear magnetic hydrogen spectrum of a complex of an alkyl diol and an alkyl dicarboxylic acid with a host 1. Fig. 19 is a schematic diagram showing the conformation of the alkyl diol and the alkyl dicarboxylic acid in the main body 1.
FIG. 20 is the nuclear magnetic hydrogen spectrum and object structure diagram of the supermolecule cup 1 complexing ibuprofen medicine molecule.
Detailed Description
The above-described scheme is further illustrated below with reference to specific embodiments, which are detailed below:
the first embodiment is as follows:
in this embodiment, a water-soluble benzotriazole supermolecular cup compound, in which the benzotriazole group has weak electron deficiency effect, can further generate a stable cyclic hydrogen bond array in an aqueous phase, and forms a stable host-guest complex in the process of molecular recognition.
In this embodiment, a preparation method of a water-soluble benzotriazole supermolecule cup compound includes the following synthesis steps:
a. in a 250mL round-bottom flask, at a low temperature of 0 ℃, 0.5mmol of an octaminohydrochloride precursor is dissolved in 100mL of a mixed solvent of acetic acid and water, wherein the mass fraction of water in the mixed solvent of acetic acid and water is 20%, and sodium nitrite (160mg,4.4equiv) is slowly added to the mixed reaction solution in two batches; the reaction mixture was then reacted for 30 minutes in an ice-water bath; then removing the ice bath, allowing the reaction mixture to reach room temperature, and stirring for reacting for 16 hours to precipitate light orange solid; after the reaction is finished, adding 50mL of water into the product mixed solution, standing, filtering, collecting a filter cake, and then fully washing by using a water-ethanol mixed solution with a volume ratio of 1:1 to obtain a light yellow product of 564mg, which is pure enough and used for the next reaction, wherein the yield is more than or equal to 90%;
b. dissolving the yellow solid product prepared in the step a in methanol, filtering the yellow solid product to remove insoluble substances after the yellow solid product is dissolved, collecting filtrate, and performing rotary evaporation on the filtrate to obtain a chloropropyl benzotriazole supermolecule cup;
c. in a reaction bottle, dissolving 100mg of the chloropropyl benzotriazole supermolecule cup prepared in the step b in 10mL of N-methylimidazole, and heating at the temperature of 100 ℃ overnight under the protection of nitrogen; after the reaction is finished, cooling the product to room temperature, adding 50mL of acetone into the product, stirring for 2 hours, standing, filtering the precipitated brown solid, washing with 20mL of acetone, and collecting the solid product; then carrying out post-treatment on the solid, dissolving the collected solid product in 20mL of methanol, carrying out vacuum concentration under reduced pressure, filtering to remove trace solids, and evaporating the filtrate to obtain the solid again; then recovering the solid and suspending the solid in 30mL of acetone, and heating and refluxing the solid for 4h at 60 ℃ to obtain a suspension; and then cooling the suspension to room temperature, filtering, fully washing the solid with acetone, performing vacuum drying, and recovering to obtain 90mg (84%) of a light brown solid product, namely the benzotriazole supermolecule cup compound.
500 μ L of the subject aqueous solution of this example and about 2 μ L of the guest were added together to the nuclear magnetic tube, and the nuclear magnetic hydrogen spectrum was detected after 30 minutes of ultrasonic treatment.
Characterization of the intermediate product prepared in this example, i.e. a yellow solid product: detection of1H NMR,13C NMR and HR-MS spectra are shown in the attached appendix.1H NMR(600MHz,Chloroform-d)δ7.91(d,J＝9.8Hz,8H),7.65-7.48(m,4H),7.35-7.18(m,4H),5.75(dt,J＝11.3,7.9Hz,4H),3.72(q,J＝5.9Hz,8H),2.46(q,J＝8.8Hz,8H),1.88(dt,J＝11.2,5.2Hz,8H).13C NMR(150MHz,Chloroform-d)δ155.6,153.7,151.4,140.4,135.0,130.4,123.3,116.5,111.6,105.1,44.9,33.0,31.0,29.3.HR-MS(ESI):Calcd.for chemical formula C64H48Cl4N12O8:1252.2472,found:1275.2356[M+Na]+.
Characterization of the final product prepared in this example: detection of1HNMR,13C NMR and HR-MS spectra are shown in the attached appendix.1H NMR(600MHz,Methanol-d4)δ9.17(s,4H),8.17(s,4H),8.05(s,4H),7.83(s,8H),7.64(s,4H),5.67(t,J＝8.5Hz,4H),4.50(t,J＝6.8Hz,8H),3.98(s,12H),2.81(q,J＝8.4Hz,8H),1.99(dt,J＝13.9,7.0Hz,8H).13C NMR(150MHz,Methanol-d4)δ155.7,136.6,135.1,135.1,125.5,123.7,123.7,122.5,122.5,116.1,49.6,35.2,33.6,28.9,28.2.HR-MS(ESI):Calcd.for chemical formula C80H72N20O8·4Cl:1580.4596,found:755.2593[M-2Cl]2+,491.8505[M-3Cl]3+.
The NMR spectrum of the compound of this example is shown in FIGS. 3 to 9, in which active hydrogens are present in the benzotriazolyl group of the compound and the positions of the active hydrogens are not fixed. The main body is C in both organic phase and aqueous phase4vA symmetrical configuration of (a) exists. The supermolecule cup of the embodiment can form a 1:1 host-guest complex with various types of guests in the water phase. The existence of active hydrogen on the upper edge of the host can be complemented with water molecules to form annular hydrogen bonds, and the stability of the host-guest complex is further stabilized through the action of the hydrogen bonds.
Example two:
this embodiment is substantially the same as the first embodiment, and is characterized in that:
in this example, a solution of straight paraffin was added to a water-soluble supramolecular cup 1 (500. mu.L, 1mM in D)2O), equivalent ratio was excess (2 μ L) and guest: and (3) carrying out ultrasonic treatment on the mixed solution for 1 hour, and detecting a nuclear magnetic resonance hydrogen spectrum. And analyzing the hydrogen spectrum of the nuclear magnetic resonance, and simultaneously verifying whether the self-assembly behavior exists in the main body. By analyzing their high-field characteristic signals, small to medium-sized linear alkanes (C5-C10) form 1:1 host-guest complexes with 1, and free guest signal peaks appear in 0.8-1.2ppm blocks. From n-pentane to n-heptane, the guest molecules were completely in the host cavity, and a broad nuclear magnetic signal was observed in the high field region, indicating that the guests rapidly rotated and tumbled in the host. The guest signal peaks become clear for n-octane to n-decane and the resulting chemical shifts are an average due to the fast motion of the guest, all hydrogen occupying almost the same magnetic environment in the cavity. For C9-C11 linear alkanes, the methyl signal appears at the highest field, indicating a helical conformation in which the guest tumbles rapidly in the cavity, see FIGS. 10-13. The triazolyl group and water molecule form a ring-shaped hydrogen bond to stabilize the stability of the host-guest complex. Longer 12<nC<The 15 alkanes showed dispersed methylene signals in the high field region and their methyl groups had a chemical shift value of-4.2 ppm, indicating that they are very close to the base of the cavity. By calculating the maximum nuclear magnetic shielding value delta & lt-5 ppm for the guest, the linear alkane is located deeper and more favorably in the 1 position than in the ureido host, which indicates that the cavity of the host is closer to the guest and stronger shielding effect occurs, see fig. 12-13.
Example three:
this embodiment is substantially the same as the previous embodiment, and is characterized in that:
in this example, a solution of the hydrophobe compound cycloparaffins (2. mu.L) was added as guest to the benzotriazole supermolecular cup 1 (500. mu.L, 1mM in D)2O), detecting a nuclear magnetic resonance hydrogen spectrum after the mixed solution is subjected to ultrasonic treatment for 1 hour. Analyzing and comparing the obtained nuclear magnetic resonance hydrogen spectrumThe subject-object recognition behavior is analyzed, see fig. 14. The guest molecules are free to rotate, tumble in the cavity, and all hydrogen is in the same chemical environment, so the high field region shows a single signal peak. As the size of the cyclic guest molecules increases, the Δ δ distribution gradually decreases, indicating that smaller guests occupy deeper positions within the cavity. The deepest displacement value Δ δ of the guest molecule is-4.5 ppm, indicating that host 1 forms a host-guest complex with the guest more stable than the ureido supramolecular cup.
Example four:
this embodiment is substantially the same as the previous embodiment, and is characterized in that:
in this example, functionalized cyclic alkanes (cycloalkyl carboxylic acids, cyclic ketones or cyclic alcohols) are amphiphilic compounds, hydrophobic depending on their ring size and hydrophilic of the functional groups, which occupy the cavity of 1 and form stable 1:1 host-guest complexes, see fig. 15. The hydrophilic acid, ketone or alcohol functional group is oriented toward the bulk of the aqueous solvent at the body cavity opening. Larger cyclododecanone can also be complexed with the host, more rigid adamantane can also be complexed with the host, and smaller cycloalkyl carboxylic acids with good water solubility can also be complexed with 1. The presence of the hydrophilic group results in the guest molecule not being able to freely tumble in the cavity and thus shows a dispersed methylene signal in the high field region.
Example five:
this embodiment is substantially the same as the previous embodiment, and is characterized in that:
in this example, the linear alkyl alcohol and alkyl carboxylic guest can also form a stable complex with 1, see fig. 16. The hydrophilic hydroxyl and carboxyl groups of these guest molecules tend to be in water, while long alkyl chains are inserted straight into the hydrophobic cavity of host 1, the methyl group is at the deepest part of the cavity (Δ δ ═ 4.9ppm), and methylene peaks are distributed one by one in the cavity until the opening. For n-dodecanol and n-dodecanoic acid, which have the same alkyl chain length and similar hydrophilicity, both have broad signal peaks in high field region due to the main body and D2The object in the O solution is subjected to rapid exchange. N-tridecanol and n-tridecanoic acid show sharp lettersPeak number, comparing the two complex hydrogen spectrograms, the recognition behaviors of the host and the object are very similar, the difference of delta is only 0.1ppm, which shows that the two different substituents do not influence the binding depth of the host and the object, and the conformation is shown in fig. 17. Through studying a series of complexation behaviors of alkyl alcohol and alkyl carboxylic acid, we find that the alkyl chain length does not influence the insertion of an object into a cavity of a host, and the alkyl part is not bent to adapt to the host, so that the phenomenon has great innovation with the recognition behaviors of the ureido and octamethylureido hosts reported previously.
Example six:
this embodiment is substantially the same as the previous embodiment, and is characterized in that:
in this example, the host-guest complexation behavior of amphiphilic disubstituted compounds such as long chain fatty diacids or diols is destined for the hydrophilic group to face the opening of the supramolecular cup 1, and the alkyl moiety to enter the cavity due to hydrophobic interaction, see fig. 18. However, the depth of the different long chain alpha, omega-diols or diacids after complexation is also different. Their highest field signal is-3.1 ppm, Δ δ -4.4ppm, which is represented by a folded chain with a-CH fixed near the bottom of the cavity2This is similar to the recognition behavior of octamethylureido hosts in that nonanediol and azelaic acid cause too fast host-guest exchange due to the short alkyl chain, signals after complexation cannot be clearly observed at high fields, and bifunctional guest hydrophobic carbon chains up to 11 methylene groups adapt to the environment of magnetic shielding inside the cavity, and the methylene groups occupy the cavity symmetrically and fold into a "U" shaped conformation inside the cavity, see fig. 19.
Example seven:
this embodiment is substantially the same as the previous embodiment, and is characterized in that:
in this example, we performed molecular recognition studies using linear alkanes and aryl vinyl guest molecules of different lengths in order to verify whether the host has self-assembly behavior. The nuclear magnetic hydrogen spectrum of the long-chain alkane complexed with the main body is analyzed, and the nuclear magnetic hydrogen spectrum can be known by referring to fig. 12: n-undecane is in a helical tumbling conformation within the body; when the guest is n-dodecane, two types of signal peaks (represented by grey stars) appear in a high field, wherein the highest field region of one group of signals is at a position of-4.2 ppm and has stronger intensity, and the maximum shielding value delta at the moment is approximately equal to-5 ppm and can be a molecular capsule; when the guest molecule is n-tetradecane, it is at the deepest at-4.2 ppm, but its methylene peak position is consistent, which is different from the molecular capsule reported before, and when different linear alkane molecules are encapsulated, the methyl peak position is consistent, but the methylene position is inconsistent. Therefore, the host may not form a molecular capsule, and the longer chain guest molecule is always the alkyl group inserted into the cavity of the host and does not bend, and the conformation is shown in fig. 13, and the condition that the alkane compound does not fold and bend under the condition that the metal does not participate in coordination is very rare.
Example eight:
this embodiment is substantially the same as the previous embodiment, and is characterized in that:
in this embodiment, in order to verify whether the supramolecular cup 1 can carry drug molecules, ibuprofen drug molecules are selected to be complexed with the supramolecular cup 1, and a nuclear magnetic hydrogen spectrum shows that the ibuprofen drug molecules are captured by the supramolecular cup 1, wherein a methyl group signal is at a position of-4.05 ppm of the highest field and has strong strength, and the maximum shielding value delta is about-4.9 ppm at the time, which shows that the ibuprofen drug molecules are firmly captured, and a methyl group points to the bottom of the supramolecular cup, as shown in fig. 20. The supermolecule cup is expected to be applied to the transportation and release of the medicine in the future.
In summary, the preparation method and application of the water-soluble benzotriazole supermolecule cup in the above embodiment are provided. Resorcinol and 2, 3-dihydrofuran are taken as initial raw materials, ring opening of furan and methylene bridging cyclization are carried out to obtain the resorcinol calixarene, and electrophilic substitution reaction and SnCl are carried out2Reducing to obtain a tetrachloropropyl octa-amino hydrochloride intermediate, and then constructing a benzotriazole supermolecular cup through similar diazotization reaction. The preparation method has the advantages of simple route and process, easily obtained raw materials, mild reaction conditions, high yield and good repeatability. The benzotriazole group in the benzotriazole water-soluble supermolecule cup structure disclosed by the invention has active proton hydrogen, so that a ring-shaped hydrogen bond array is formed under the assistance of water molecules, and the main body has very strongThe host-guest recognition performance shows good host-guest complexation behavior in a water phase.
The embodiments of the present invention have been described above with reference to the accompanying drawings, but the present invention is not limited to the above embodiments, and various changes can be made according to the purpose of the invention, and any changes, modifications, substitutions, combinations or simplifications made according to the spirit and principle of the technical solution of the present invention should be replaced with equivalents as long as the object of the present invention is met, and the technical principle and the inventive concept of the present invention are not departed from the scope of the present invention.
Claims (10)
1. A water-soluble benzotriazole supermolecule cup compound is characterized in that: the benzotriazol group in the compound has weak electron deficiency effect, so that a stable annular hydrogen bond array can be generated in a water phase, and a stable host-guest complex is formed in the process of molecular recognition.
2. The water-soluble benzotriazole supermolecule cup compound of claim 1, which is characterized in that: the benzotriazol group in the structure of the compound has active hydrogen, the calixarene presents four different active hydrogen positions, and when all the active hydrogen points in the same space direction, water molecules in the water phase and the active hydrogen on the upper edge of the main body form an annular hydrogen bond array, so that a host-guest complex in the water phase is stabilized.
3. The water-soluble benzotriazole supermolecule cup compound of claim 1, which is characterized in that: the structural formula of the compound is as follows:
4. a preparation method of the water-soluble benzotriazole supermolecule cup compound of claim 1 is characterized in that: the method comprises the following synthetic steps:
a. at a low temperature of not higher than 0 ℃, dissolving the octaminohydrochloride precursor in a mixed solvent of acetic acid and water, and slowly adding sodium nitrite into the mixed reaction solution in two batches; then reacting the reaction mixture in an ice-water bath for at least 30 minutes; then removing the ice bath, allowing the reaction mixture to reach room temperature, and stirring for at least 16 hours to react, wherein light orange solid is separated out; after the reaction is finished, adding at least 50mL of water into the product mixed solution, standing, filtering, collecting a filter cake, and then fully washing with a water-ethanol mixed solution with a volume ratio of 1:1 to obtain a light yellow product;
b. dissolving the yellow solid product prepared in the step a in methanol, filtering the yellow solid product to remove insoluble substances after the yellow solid product is dissolved, collecting filtrate, and performing rotary evaporation on the filtrate to obtain a chloropropyl benzotriazole supermolecule cup;
c. in a reaction bottle, dissolving 100mg of chloropropyl benzotriazole supermolecular cup prepared in the step b in at least 10mL of N-methylimidazole, and heating at the temperature of not higher than 110 ℃ overnight under the protection of nitrogen; after the reaction is finished, cooling the product to room temperature, adding acetone into the product, stirring, standing, filtering, washing with acetone, and collecting a solid product; and then carrying out post-treatment on the solid to obtain the benzotriazole supermolecule cup compound.
5. The preparation method of the water-soluble benzotriazole supermolecule cup compound of claim 4, which is characterized in that: in the step a, 0.5mmol of the octaamino hydrochloride precursor is dissolved in at least 100mL of a mixed solvent of acetic acid and water, wherein the mass fraction of water in the mixed solvent of acetic acid and water is not more than 20%.
6. The preparation method of the water-soluble benzotriazole supermolecule cup compound of claim 4, which is characterized in that: in the step c, when the post-treatment is carried out, the collected solid product is dissolved in methanol, vacuum concentration is carried out under reduced pressure, filtration is carried out to remove trace solids, and the filtrate is evaporated to obtain solids again; then recovering the solid and suspending the solid in acetone, and heating and refluxing for at least 4h at the temperature of not less than 60 ℃ to obtain a suspension; and then cooling the suspension to room temperature, filtering, fully washing the solid with acetone, and performing vacuum drying to obtain the benzotriazole supermolecule cup compound.
7. The preparation method of the water-soluble benzotriazole supermolecule cup compound of claim 6, which is characterized in that: when vacuum concentration is carried out, the temperature is not higher than 45 ℃, and the vacuum degree is 0.09-0.1 MPa.
8. The preparation method of the water-soluble benzotriazole supermolecule cup compound of claim 4, which is characterized in that: in the step c, the obtained benzotriazole supermolecular cup compound and D2And mixing O, shaking to prepare a clear high-dilution water solution, and storing.
9. The application of the water-soluble benzotriazole supermolecule cup compound of claim 1 is characterized in that: the conformation transformation is carried out in the water phase, a cavity is generated, and further, a guest molecule is identified, wherein the guest molecule is at least one of straight-chain alkane, cyclane, cycloalkanol, cyclic carboxylic acid, cyclic ketone, alkyl alcohol, alkyl carboxylic acid, alkyl diol, alkyl dicarboxylic acid and ibuprofen medicament.
10. The application of the water-soluble benzotriazole supermolecule cup compound of claim 9, which is characterized in that: the water-soluble benzotriazole supermolecule cup compound forms a 1:1 host-guest complex with guest molecules in a water phase.
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