CN110372469B - Hydrogenated cyclo [12] arene compound and preparation method thereof - Google Patents

Hydrogenated cyclo [12] arene compound and preparation method thereof Download PDF

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CN110372469B
CN110372469B CN201910667621.8A CN201910667621A CN110372469B CN 110372469 B CN110372469 B CN 110372469B CN 201910667621 A CN201910667621 A CN 201910667621A CN 110372469 B CN110372469 B CN 110372469B
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王梅祥
时谈浩
佟硕
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Tsinghua University
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Abstract

The invention discloses a hydrogenated endless belt [12]]Aromatic hydrocarbon compounds and a process for producing the same. The compound is a compound shown in a formula (I) or a stereoisomer of the compound shown in the formula (I), and the preparation method comprises the following steps: alkenylated cups [6] in organic solvents]Aromatic hydrocarbon derivative compound or calix [6] of formula (II)]The aromatic hydrocarbon alcohol derivative compound shown in formula (III) reacts with acidThe hydrogenated ring belt [12] can be obtained through intramolecular cyclization reaction]Aromatic hydrocarbon compounds of formula (I). The invention selects cheap and easily available raw materials, namely the cup [6]]Starting from resorcinol, the calix [6] can be prepared in large scale by the steps of selective methylation, trifluoromethanesulfonylation, transition metal catalytic coupling, Grignard reagent addition and the like]The arene derivative shown in the formula (II) and the compound shown in the formula (III) is further subjected to intramolecular Friedel-crafts alkylation reaction to conveniently prepare hydrogenated ring belt [12]]An aromatic hydrocarbon compound. The reaction condition is relatively mild, and the obtained product is stable in the air and easy to separate and purify, thereby having good practicability and application prospect.

Description

Hydrogenated cyclo [12] arene compound and preparation method thereof
Technical Field
The invention relates to the field of organic chemistry, in particular to a hydrogenated cyclo [8] arene compound and a preparation method thereof.
Background
The artificially synthesized macrocyclic compound has the characteristics and advantages of good molecular structure designability and physical and chemical property adjustability, and is widely applied to various fields of chemistry, material science and life science. As a host compound, the artificially synthesized macrocyclic compound can identify anions and cations and neutral guest molecules, so that the macrocyclic compound is applied to separation, sensing and detection. As a motif or template, functionalized macrocyclic compounds are used in the construction of functional assemblies and nanomaterials and molecular machines. The macrocyclic compound also provides a unique research means and approach for exploring chemical reaction mechanisms and supramolecular catalysis.
To date, a large number of artificially synthesized macrocyclic compounds have been reported in the literature, wherein crown ethers, sphenol, chemically modified cyclodextrin derivatives, calixarenes, cyclotriveratryl hydrocarbons, calixarenes, cucurbiturils, heterocalixarenes, Cycloparaphenylenes (CPPs), pillared arenes, coronenes, and the like are becoming dominant macrocyclic host molecules, and have been studied relatively deeply and extensively. Because different macrocyclic compounds have different structures, the sizes, shapes and electronic characteristics of cavities of the macrocyclic compounds are different, thereby showing different molecular recognition capabilities. Thus, there is still a need for a macrocyclic compound having a novel structure and function.
Disclosure of Invention
The present invention is directed to solving, at least to some extent, one of the technical problems in the related art. To this end, an object of the present invention is to propose a hydrogenated cyclo [12] arene compound and a method for producing the same. The compound has a barrel-shaped cavity structure, the volume size of the cavity is variable, the polarity of the inner wall of the cavity is adjustable, and the compound has a wide application prospect.
In one aspect of the invention, the invention features a compound. According to an embodiment of the invention, the compound is a compound of formula (I) or a stereoisomer of a compound of formula (I),
Figure BDA0002140642030000021
wherein the content of the first and second substances,
R1、R2and R3Each independently is a hydrogen atom, optionally substituted C1-12Alkyl, optionally substituted C1-12Heteroalkyl, optionally substituted C2-12Alkenyl, optionally substituted C5-24Cycloalkyl or optionally substituted C5-24A heterocyclic group.
The compound of the embodiment is also called 'hydrogenated ring belt [12] arene compound', and the compound has a barrel-shaped cavity structure, the size of the cavity volume is variable, and the polarity of the inner wall of the cavity is adjustable. As a novel artificially synthesized macrocyclic molecule, the hydrogenated cyclo [12] arene shown in the formula (I) can selectively recognize organic molecules from a mixed solution and form an inclusion complex, so that the hydrogenated cyclo [12] arene can be applied to separation of organic small molecules.
In addition, the compounds according to the above embodiments of the present invention may also have the following additional technical features:
according to an embodiment of the invention, R1、R2And R3May be independently a hydrogen atom or C1-6Alkyl radical, C1-6Heteroalkyl group, C2-6Alkenyl radical, C5-12Cycloalkyl radical, C5-12A heterocyclic group.
According to an embodiment of the invention, R1And R2May each independently be a hydrogen atom, a methyl group, an ethyl group, a n-propyl group, a n-butyl group, a phenyl group or an optionally substituted phenyl group; r3Can be ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-pentyl, n-hexyl, n-heptyl, n-octylN-nonyl, n-decyl, benzyl, p-methylbenzyl, o-methylbenzyl or m-methylbenzyl.
According to an embodiment of the present invention, the optionally substituted phenyl group may be a 2-methylphenyl group, a 3-methylphenyl group, a 4-methylphenyl group, a 2-ethylphenyl group, a 3-ethylphenyl group, a 4-ethylphenyl group, a 2-isopropylphenyl group, a 3-isopropylphenyl group, a 4-isopropylphenyl group, a 3, 4-dimethylphenyl group, a 3, 5-dimethylphenyl group, a 3, 6-dimethylphenyl group, a 2, 3-dimethylphenyl group, a 2, 4-dimethylphenyl group, a 2, 5-dimethylphenyl group, a 2, 6-dimethylphenyl group, a 3, 4-diethylphenyl group, a 3, 5-diethylphenyl group, a 3, 6-diethylphenyl group, a 2, 3-diethylphenyl group, a 2, 4-diethylphenyl group, a 2, 5-diethylphenyl group, a, 2, 6-diethylphenyl or 3,4, 5-trimethylphenyl.
According to embodiments of the invention, the compound may have the structure of one of:
Figure BDA0002140642030000031
in another aspect of the invention, the invention provides a method of making the compounds of the above examples. According to an embodiment of the invention, the method comprises: contacting a first raw material or a second raw material with an acid to obtain a compound represented by formula (I), wherein the first raw material comprises at least one of a compound represented by formula (IIa) and a compound represented by formula (IIb), and the second raw material comprises at least one of a compound represented by formula (IIIa) and a compound represented by formula (IIIb),
Figure BDA0002140642030000032
Figure BDA0002140642030000041
wherein R is1And R3As previously described. In some embodiments, the first starting material is a mixture of compounds of formula (IIa) and compounds of formula (IIb), and the second starting material is a mixture of compounds of formula (IIIa) and compounds of formula (IIIb).
According to the embodiment of the invention, the first raw material or the second raw material can be subjected to intramolecular Friedel-crafts alkylation reaction under the action of acid to obtain the compound shown in the formula (I), the reaction condition is mild, and the obtained product is stable in air, easy to separate and purify and has good practicability and application prospect.
In addition, the method for preparing the compound according to the above embodiment of the present invention may further have the following additional technical features:
according to an embodiment of the present invention, the acid may include at least one selected from the group consisting of polyphosphoric acid, hydrochloric acid, sulfuric acid, trifluoromethanesulfonic anhydride, trimethylsilyl trifluoromethanesulfonate, methanesulfonic acid, p-toluenesulfonic acid, perfluorosulfonic acid resin (Nafion resin), and scandium trifluoromethanesulfonate. Therefore, the reaction conditions can be milder, and the cyclization/polymerization ratio of the product is higher. According to a preferred embodiment of the present invention, the above acid includes at least one selected from the group consisting of trifluoromethanesulfonic acid and methanesulfonic acid, whereby the yield and selectivity of the product can be further improved.
According to an embodiment of the present invention, the contacting is performed in a first solvent, and the first solvent may include at least one selected from the group consisting of benzene, toluene, trifluorotoluene, chlorobenzene, fluorobenzene, nitrobenzene, bromobenzene, dichloromethane, 1, 2-dichloroethane, 1,2, 2-tetrachloroethane, and chloroform. According to some embodiments of the present invention, when preparing the compound of formula (I) from a first starting material, the first solvent is preferably 1, 2-dichloroethane; in the case of preparing the compound represented by the formula (I) from the second starting material, the first solvent is preferably dichloromethane. Therefore, the requirements of the reaction temperature on the solvent can be met while providing good solubility for the raw materials.
According to the embodiment of the invention, the contact can be carried out at-40-150 ℃ for 0.1-48 h. According to some embodiments of the present invention, when the compound of formula (I) is prepared from the first raw material, the contacting is preferably performed at 25-50 ℃ for 2 h; in the preparation of the compound of formula (I) from the second starting material, the above contacting is preferably carried out at 0 ℃ for 0.2 h. Thereby, the yield and selectivity of the product can be further improved.
According to the embodiment of the invention, the dosage ratio of the first raw material to the acid can be 0.01-1 mmol: 0.01-100 mmol, preferably 0.1mmol:0.3 mmol; the dosage ratio of the second raw material to the acid can be 0.01-1 mmol: 0.01-10 mL, and preferably 0.1mmol:0.2 mL. In addition, the amount of the solvent used in the reaction is not particularly limited, and according to some embodiments of the present invention, the ratio of the amount of the first raw material, the acid, and the first solvent may be 0.01 to 1mmol:0.01 to 100mmol:0.5 to 300mL, preferably 0.1mmol:0.3mmol:5 mL; the ratio of the amount of the second raw material, the acid and the first solvent may be 0.01 to 1mmol, 0.01 to 10mL, 2 to 500mL, preferably 0.1mmol, 0.2mL10 mL. In addition, when the first raw material is a mixture of the compound represented by the formula (IIa) and the compound represented by the formula (IIb), and the second raw material is a mixture of the compound represented by the formula (IIIa) and the compound represented by the formula (IIIb), the amount used in the above-mentioned compounding ratio is the total amount of the compound represented by the formula (IIa) and the compound represented by the formula (IIb) or the total amount of the compound represented by the formula (IIIa) and the compound represented by the formula (IIIb).
According to the embodiment of the present invention, the compound represented by formula (IIa) can be prepared by subjecting the compound represented by formula (VIa) to a first cross-coupling reaction under the action of a first metal catalyst, the compound represented by formula (IIb) is prepared by subjecting the compound represented by formula (VIb) to a first cross-coupling reaction under the action of a first metal catalyst, and thus the compound represented by formula (IIa) and the compound represented by formula (IIb) can be prepared in a large amount from calix [6] resorcinals, which have abundant modifiable sites and can form many different derivatives including molecular cage structures after chemical reaction or be chemically modified and then form molecular capsules through molecular self-assembly, etc.,
Figure BDA0002140642030000051
according to an embodiment of the present invention, the above-mentioned first metal catalyst may include at least one selected from the group consisting of tetrakistriphenylphosphine palladium, tris (dibenzylideneacetone) dipalladium, palladium chloride or [1, 1' -bis (diphenylphosphino) ferrocene ] dichloropalladium, preferably tetrakistriphenylphosphine palladium.
According to an embodiment of the present invention, the above-mentioned first cross-coupling reaction is performed in a second solvent, and the second solvent may include at least one selected from the group consisting of N, N-dimethylformamide, N-dimethylaniline, N-dimethylacetamide, N-methylpyrrolidone, tetrahydrofuran, 1, 4-dioxane, water, and dimethylsulfoxide. According to some embodiments of the invention, when the compound of formula (I) of interest is R1When H, the second solvent is preferably N, N-dimethylformamide; when the target compound of formula (I) is R1When other substituents are present, the second solvent is preferably a mixed solution of 1, 4-dioxane and water. By adopting the solvent, the yield of the product can be further improved, the side reaction is reduced, and the product is easy to separate.
According to an embodiment of the present invention, the first cross-coupling reaction is performed under the action of an additive and an alkenylation reagent, the additive may include at least one selected from the group consisting of potassium carbonate, cesium carbonate, lithium carbonate, sodium chloride and lithium chloride, and the additive may effectively participate in a catalytic cycle in the cross-coupling reaction, thereby improving reaction efficiency. According to some embodiments of the invention, when the compound of formula (I) of interest is R1When H, the additive is preferably lithium chloride; when the target compound of formula (I) is R1In the case of other substituents, the additive is preferably potassium carbonate. Thus, the yield of the product can be further improved, side reactions can be reduced, and the product can be easily separated. The alkenylation reagent may include at least one selected from the group consisting of vinylmagnesium bromide, isopropenylmagnesium bromide, tributylvinylene, tributylisopropenylene, isopropenylboronic acid pinacol ester, and vinylboronic acid pinacol ester. When the target compound of formula (I) is R1When H, the alkenylation agent is preferably tributylvinylene; when the target compound of formula (I) is R1In the case of other substituents, the alkenylating agent is preferably isopropenylboronic acid pinacol ester. Thus, the yield of the product can be further improved, side reactions can be reduced, and the product can be easily separated.
According to embodiments of the invention, the first cross-coupling reaction may be atAnd (3) performing the reaction for 6-36 hours at the temperature of 25-140 ℃. According to some embodiments of the invention, when the compound of formula (I) of interest is R1When H, the first cross-coupling reaction is preferably carried out at 120 ℃ for 12H; when the target compound of formula (I) is R1For other substituents, the first cross-coupling reaction is carried out at 110 ℃ for 24 h. Thereby, the yield of the product can be further improved.
According to the embodiment of the present invention, the compound represented by formula (IIIa) can be prepared by subjecting the compound represented by formula (IVa) to a reduction reaction under the action of a reducing agent, the compound represented by formula (IIIb) can be prepared by subjecting the compound represented by formula (IVb) to a reduction reaction under the action of a reducing agent,
Figure BDA0002140642030000061
according to an embodiment of the present invention, the reducing agent may include lithium aluminum hydride or sodium borohydride. At least one of lithium borohydride, hydrogen, red aluminum, diisobutyl aluminum hydride and borane dimethyl sulfide, preferably sodium borohydride. This can further improve the convenience of operation and reaction efficiency.
According to an embodiment of the present invention, the reduction reaction is performed in a third solvent, and the third solvent may include at least one selected from the group consisting of tetrahydrofuran, 1, 4-dioxane, ethanol, and methanol, and preferably ethanol.
According to the embodiment of the invention, the reduction reaction can be completed at-78-80 ℃ for 1-24 h, and preferably at 25 ℃ for 12 h.
According to the embodiment of the present invention, the compound represented by the formula (IVa) can be prepared by subjecting the compound represented by the formula (Va) to addition reaction with a Grignard reagent, the compound represented by the formula (IVb) can be prepared by subjecting the compound represented by the formula (Vb) to addition reaction with a Grignard reagent,
Figure BDA0002140642030000071
according to an embodiment of the present invention, the Grignard reagent may include a compound selected from the group consisting of phenylmagnesium bromide, 2-methylphenylmagnesium bromide, 3-methylphenylmagnesium bromide, 4-methylphenylmagnesium bromide, 2-ethylphenylmagnesium bromide, 3-ethylphenylmagnesium bromide, 4-ethylphenylmagnesium bromide, 2-isopropylphenylmagnesium bromide, 3-isopropylphenylmagnesium bromide, 4-isopropylphenylmagnesium bromide, 3, 4-dimethylphenylmagnesium bromide, 3, 5-dimethylphenylmagnesium bromide, 3, 6-dimethylphenylmagnesium bromide, 2, 3-dimethylphenylmagnesium bromide, 2, 4-dimethylphenylmagnesium bromide, 2, 5-dimethylphenylmagnesium bromide, 2, 6-dimethylphenylmagnesium bromide, 3, 4-diethylphenylmagnesium bromide, 3-ethylphenylmagnesium bromide, 3-isopropylphenylmagnesium bromide, 4-isopropylphenylmagnesium bromide, 3, 4-dimethylphenylmagnesium, At least one of 3, 5-diethylphenylmagnesium bromide, 3, 6-diethylphenylmagnesium bromide, 2, 3-diethylphenylmagnesium bromide, 2, 4-diethylphenylmagnesium bromide, 2, 5-diethylphenylmagnesium bromide, 2, 6-diethylphenylmagnesium bromide and 3,4, 5-trimethylphenylmagnesium bromide.
According to an embodiment of the present invention, the addition reaction is performed in a fourth solvent, and the fourth solvent may include at least one selected from the group consisting of tetrahydrofuran and 1, 4-dioxane, preferably tetrahydrofuran.
According to the embodiment of the invention, the addition reaction is carried out at-78-70 ℃ for 12-24 h, preferably at 70 ℃ for 12 h.
According to the embodiment of the present invention, the compound represented by formula (Va) may be prepared by subjecting the compound represented by formula (VIa) to a second cross-coupling reaction under the action of a second metal catalyst, and the compound represented by formula (Vb) may be prepared by subjecting the compound represented by formula (VIb) to a second cross-coupling reaction under the action of a second metal catalyst.
According to an embodiment of the present invention, the second metal catalyst may include at least one selected from the group consisting of palladium acetate, tetrakistriphenylphosphine palladium, tris (dibenzylideneacetone) dipalladium, palladium chloride and [1, 1' -bis (diphenylphosphino) ferrocene ] palladium dichloride, preferably tetrakistriphenylphosphine palladium.
According to an embodiment of the present invention, the second cross-coupling reaction is performed in a fifth solvent, and the fifth solvent may include at least one selected from the group consisting of N, N-dimethylformamide, N-dimethylaniline, N-dimethylacetamide, N-methylpyrrolidone, and dimethylsulfoxide, preferably N, N-dimethylformamide.
According to an embodiment of the present invention, the second cross-coupling reaction can be performed at 80-150 ℃ for 12-48 h, preferably at 140 ℃ for 24 h.
According to the examples of the present invention, the compound represented by the formula (VIa) can be prepared by subjecting the compound represented by the formula (VIIa) to a first trifluoromethanesulfonylation reaction, the compound represented by the formula (VIb) can be prepared by subjecting the compound represented by the formula (VIIb) to a first trifluoromethanesulfonylation reaction,
Figure BDA0002140642030000081
according to an embodiment of the present invention, the first trifluoromethanesulfonylation reaction is performed under the action of a base, and the base used in the first trifluoromethanesulfonylation reaction may include at least one selected from pyridine, triethylamine, diethylamine, N-diisopropylethylamine, 2, 6-dimethylpyridine, and potassium carbonate, and is preferably pyridine.
According to an embodiment of the present invention, the first trifluoromethanesulfonylation reaction is performed in a sixth solvent, which may include at least one selected from the group consisting of dichloromethane, chloroform, 1, 2-dichloroethane, toluene, and benzene, preferably dichloromethane.
According to the embodiment of the invention, the first trifluoromethanesulfonylation reaction can be carried out at-78-45 ℃ for 3-24 h, and preferably at 20-40 ℃ for 12 h.
According to an embodiment of the present invention, the compound represented by formula (VIIa) may be prepared by reacting the compound represented by formula (VIIIa) with an acid and hydrolyzing, the compound represented by formula (VIIb) may be prepared by reacting the compound represented by formula (VIIIb) with an acid and hydrolyzing,
Figure BDA0002140642030000082
according to an embodiment of the present invention, the above acid may include at least one of boron trichloride, boron tribromide, boron triiodide and hydrobromic acid, preferably boron tribromide. Thus, the convenience of operation and the yield of the product can be further improved.
According to an embodiment of the present invention, the reaction of the compound represented by formula (VIIa) or the compound represented by formula (VIIb) with an acid and the hydrolysis are performed in a seventh solvent, and the seventh solvent may include at least one selected from the group consisting of dichloromethane, chloroform, and 1, 2-dichloroethane, preferably dichloromethane.
According to an embodiment of the present invention, the reaction of the compound of formula (VIIa) or the compound of formula (VIIb) with an acid and hydrolysis may be performed at-20 ° to 45 ° for 6 to 24 hours, preferably at 25 ° for 12 hours.
According to the embodiment of the present invention, the compound represented by the formula (VIIIa) can be prepared by subjecting the compound represented by the formula (IXa) to a catalytic coupling reaction, the compound represented by the formula (VIIIb) can be prepared by subjecting the compound represented by the formula (IXb) to a catalytic coupling reaction,
Figure BDA0002140642030000091
according to an embodiment of the present invention, the metal catalyst used in the catalytic coupling reaction may include at least one selected from the group consisting of palladium acetate, tetratriphenylphosphine palladium, palladium carbon, tris (dibenzylideneacetone) dipalladium, palladium chloride and [1, 1' -bis (diphenylphosphino) ferrocene ] palladium dichloride, preferably tris (dibenzylideneacetone) dipalladium.
According to an embodiment of the present invention, the ligand used in the catalytic coupling reaction may include at least one selected from the group consisting of tetrakistriphenylphosphine, 1 ' -binaphthyl-2, 2 ' -bisdiphenylphosphine, 1, 3-bis (diphenylphosphine) propane, and 1,1 ' -bis (diphenylphosphine) ferrocene, preferably 1,1 ' -binaphthyl-2, 2 ' -bisdiphenylphosphine.
According to an embodiment of the present invention, the hydrogen source employed in the catalytic coupling reaction may comprise at least one selected from formic acid, ammonium acetate, triethylhydrosilane, preferably formic acid.
According to an embodiment of the present invention, the catalytic coupling reaction is performed in an eighth solvent, and the eighth solvent may include at least one selected from the group consisting of N, N-dimethylformamide, N-dimethylaniline, N-dimethylacetamide, N-methylpyrrolidone, dimethylsulfoxide, toluene, xylene, and mesitylene, and is preferably a mixed solution of toluene and xylene. This can further improve the product yield.
According to the embodiment of the invention, the catalytic coupling reaction can be completed at 80-150 ℃ for 12-72 h, preferably at 140 ℃ for 50-70 h.
According to the examples of the present invention, the compound represented by the formula (IXa) is obtained by subjecting the compound represented by the formula (Xa) to a second trifluoromethanesulfonylation reaction, the compound represented by the formula (IXb) is obtained by subjecting the compound represented by the formula (Xb) to a second trifluoromethanesulfonylation reaction,
Figure BDA0002140642030000101
according to an embodiment of the present invention, the second trifluoromethanesulfonylation reaction is performed under the action of a base, and the base used in the second trifluoromethanesulfonylation reaction may include at least one selected from pyridine, triethylamine, diethylamine, N-diisopropylethylamine, 2, 6-dimethylpyridine, and potassium carbonate, and is preferably pyridine.
According to an embodiment of the present invention, the second trifluoromethanesulfonylation reaction is performed in a sixth solvent, and the sixth solvent may include at least one selected from the group consisting of dichloromethane, chloroform, 1, 2-dichloroethane, toluene, and benzene, preferably dichloromethane.
According to the embodiment of the invention, the second trifluoromethanesulfonylation reaction can be carried out at-78-45 ℃ for 8-36 h, and preferably at 45 ℃ for 12-24 h.
According to the examples of the present invention, the compound represented by the formula (Xa) and the compound represented by the formula (Xb) are prepared by subjecting the compound represented by the formula (XI) to selective methylation reaction,
Figure BDA0002140642030000102
according to an embodiment of the present invention, the selective methylation reaction is performed under the action of a base, and the base used in the selective methylation reaction includes at least one selected from sodium carbonate, potassium carbonate, cesium carbonate and cesium fluoride, and preferably potassium carbonate.
According to an embodiment of the present invention, the methylating agent used in the selective methylation reaction may include at least one selected from methyl iodide, dimethyl sulfate and dimethyl carbonate, preferably methyl iodide.
According to an embodiment of the present invention, the selective methylation reaction is performed in a tenth solvent, and the tenth solvent may include at least one selected from the group consisting of dichloromethane, chloroform, 1, 2-dichloroethane, acetone, N-dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, and 1, 4-dioxane, preferably acetone. Thus, the convenience of the post-treatment, the reaction efficiency and the yield of the product can be further improved.
According to the embodiment of the invention, the selective methylation reaction can be completed at 25-100 ℃ for 1-12 h, preferably at 50-60 ℃ for 3 h.
According to the examples of the present invention, the compounds represented by the formula (XI) can be synthesized according to the methods reported in the literature (B.W.Purse, A.Shivanyuk, J.Jr.Rebek.chem.Commun.2002, 2612).
In another aspect of the invention, the invention proposes the use of the compounds of the above embodiments in the selective inclusion of organic molecules, for the identification and selective inclusion of organic molecules from a mixed solution. According to the embodiment of the invention, the compound shown in the formula (I) can be used as a macrocyclic host molecule to selectively recognize and include small organic molecules, so that the compound is applied to separation of the small organic molecules.
According to an embodiment of the present invention, the mixed solution includes 1, 2-dichloroethane, methanol, chloroform, ethanol, and acetonitrile. According to a specific embodiment of the present invention, the inclusion complex of the compound of the present invention with an organic molecule comprises: reacting a compound represented by the formula (Ib-1) with chloroform.
Additional aspects and advantages of the invention will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the invention.
Drawings
The above and/or additional aspects and advantages of the present invention will become apparent and readily appreciated from the following description of the embodiments, taken in conjunction with the accompanying drawings of which:
FIG. 1 is a nuclear magnetic hydrogen spectrum of a compound represented by the formula (Ia);
FIG. 2 is a nuclear magnetic carbon spectrum of a compound represented by the formula (Ia);
FIG. 3 is a nuclear magnetic hydrogen spectrum of the compound represented by the formula (Ic-1);
FIG. 4 is a nuclear magnetic carbon spectrum of the compound represented by the formula (Ic-1);
FIG. 5 is a crystal structure diagram of a complex formed by the compound represented by the formula (Ib-1) and guest chloroform.
Detailed Description
The following describes embodiments of the present invention in detail. The following examples are illustrative only and are not to be construed as limiting the invention. The examples, where specific techniques or conditions are not indicated, are to be construed according to the techniques or conditions described in the literature in the art or according to the product specifications. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products commercially available.
Example 1: preparation of Compound (Ia) (corresponding to R in formula (I))1Is CH3；R2Is CH3；R3To Et)
The reaction formula is as follows:
Figure BDA0002140642030000121
the preparation method comprises the following steps:
a mixture of the compound represented by the formula (IIa) and the compound represented by the formula (IIb) (0.1 mmol, 95.0mg) was placed in a 25mL Schlenk's tube, and dissolved by adding 5mL of dichloroethane. 0.3mmol (55. mu.L) of trifluoromethanesulfonic acid was slowly added along the vial wall using a microsyringe at room temperature and reacted for 2h at 40 ℃. After the reaction was completed, water was added to quench, the aqueous phase was extracted with dichloromethane, and the organic phases were combined and washed with a saturated sodium chloride solution, followed by drying over anhydrous sodium sulfate. The solvent was dried by spinning and separated using preparative thin layer chromatography (thickness of coating 0.9-1.1 mm, developing solvent petroleum ether/dichloromethane: 5/1) to give 20.3mg of the compound of formula (Ia) in 21% yield.
1H-NMR (400MHz, CHLOROFORM-D)7.32(s,6H),6.83(s,6H),4.08(t, J ═ 6.2Hz,3H),3.35(t, J ═ 7.8Hz,3H),2.14-2.18(m,6H),1.99-2.06(m,6H),1.77(s,9H),1.70(s,9H),1.67(s,9H),1.54(s,9H),1.36(t, J ═ 7.1Hz,9H),1.17(t, J ═ 7.3Hz, 9H); (as in FIG. 1)
13C-NMR (101MHz, CHLOROFORM-D)145.0,142.9,140.5,137.8,124.48,112.0,50.5,41.9,41.2,39.4,36.2,32.3,27.5,26.9,25.3,20.4,14.0, 13.7; (see fig. 2)
HRMS(APCI)calcd.for C72H83 -:[M-H]-m/z 947.6500,found 947.6509.
As can be seen from the above, the compound has a correct structure and is represented by the formula (Ia).
The compounds of formula (IIa) and (IIb) are prepared as follows:
Figure BDA0002140642030000131
a25 mL Schlenk bottle was charged with 0.08mmol (128mg) of a mixture of the compound of the formula (VIa) and the compound of the formula (VIb), 0.12mmol (139mg) of tetratriphenylphosphine palladium, 1.92mmol (265mg) of potassium carbonate, 2.75mL1, a mixed solution of 4-dioxane and water (v/v. RTM. 4.5/1) and 0.12mmol (0.14mL) of isopropenylboronic acid pinacol ester. The reaction was then placed in an oil bath at 110 ℃ for 24 h. After the reaction, the reaction system was extracted with ethyl acetate, and the organic phases were combined and washed with 5% hydrogen peroxide and saturated sodium chloride solution. Followed by drying over anhydrous sodium sulfate. The compound represented by the formula (IIa) and the compound represented by the formula (IIb) were separated by solvent spin-dry column chromatography (silica gel 100 to 200 mesh, eluent: petroleum ether/dichloromethane: 12:1) to obtain 54.1mg in total, and the yield was 71%.
IIa：
1H-NMR(400MHz,CHLOROFORM-D)7.31-7.56(m,6H),6.90-7.04(m,11H),6.75(s,1H),5.15-5.28(m,6H),4.66-4.89(m,6H),4.03-4.18(m,6H),1.80-2.11(m,30H),0.68-0.87(m,18H)；
13C-NMR(101MHz,CHLOROFORM-D)145.8,145.7,145.5,145.4,145.2,145.2,145.1,144.2,144.1,144.1,143.9,143.8,143.8,142.4,142.4,142.3,142.2,142.1,141.5,141.4,141.1,141.0,140.9,140.8,140.8,140.7,140.6,140.5,140.4,140.3,140.0,128.0,127.9,127.7,127.6,127.5,127.4,127.3,127.2,127.1,124.8,124.5,124.4,124.3,124.1,123.9,123.8,123.7,123.6,123.4,123.2,115.7,115.6,115.6,115.4,115.3,115.1,77.3,77.2,77.0,76.7,48.4,48.2,48.1,47.8,47.8,47.6,47.5,47.4,47.4,29.9,29.8,29.6,29.4,29.3,29.2,26.2,26.1,26.0,25.9,25.9,25.8,25.7,25.7,13.1,13.1,12.94 12.8；
HRMS(APCI)calcd.for C72H85 +:[M+H]+m/z 949.6646,found 949.6655.
IIb：
1H-NMR(400MHz,CHLOROFORM-D)7.35-7.57(m,6H),6.89-7.05(m,10H),6.74-6.75(m,2H),5.04-5.23(m,6H),4.73-4.89(m,6H),4.02-4.17(m,6H),1.82-2.10(m,30H),0.68-0.78(m,18H)；
13C-NMR(101MHz,CHLOROFORM-D)146.0,145.9,145.8,145.8,145.7,145.7,145.6,145.5,144.4,144.2,142.4,142.3,142.1,142.0,141.5,141.2,141.2,141.0,140.9,140.9,140.9,140.8,140.6,140.6,140.5,140.4,140.3,128.0,128.0,127.9,127.9,127.8,127.7,127.4,125.5,125.3,125.1,124.9,124.7,124.4,124.3,124.1,124.0,123.6,123.5,123.2,123.2,122.9,115.7,115.6,115.5,48.4,48.3,48.2,48.1,48.0,47.9,47.9,47.8,30.0,29.8,29.7,29.7,29.6,29.5,26.2,26.2,26.1,26.0,13.3,13.2,13.1；
HRMS(APCI)calcd.for C72H85[M+H]+m/z 949.6646,found 949.6655.
As is clear from the above, the above compounds have correct structures and are represented by the formula (IIa) and the formula (IIb), respectively.
The preparation method of the compound shown in the formula (VIa) and the compound shown in the formula (VIb) is as follows:
Figure BDA0002140642030000141
a mixture of 15mmol (1.2g) of the compound represented by the formula (VIIa) and the compound represented by the formula (VIIb), 15mL of dichloromethane and 27mmol (2.2mL) of pyridine was placed in a 50mL three-necked flask, and after stirring uniformly at room temperature, the system was placed in an ice-water bath, and 18mmol (3mL) of trifluoromethanesulfonic anhydride was slowly added to the system using a 10mL constant-pressure dropping funnel. After dropping, the system was heated to reflux and the reaction was continued for 12 h. After the reaction was completed, the reaction solution was quenched by slowly adding ice water, the aqueous phase was extracted with dichloromethane, and the combined organic phases were washed with saturated brine and dried over anhydrous sodium sulfate. And (3) separating the solvent by spin-drying column chromatography (silica gel 100-200 meshes, eluent: petroleum ether/dichloromethane: 4/1) to obtain 1.66g of the compound shown in the formula (VIa) and the compound shown in the formula (VIb) in total, wherein the yield is 69%.
VIa：
1H-NMR(400MHz,CHLOROFORM-D)7.28-7.35(m,3H),7.07-7.25(m,15H),4.13-4.25(m,6H),1.86-1.91(m,12H),0.75-0.80(m,18H)
19F-NMR(376MHz,CHLOROFORM-D)-73.29,-73.35,-73.44,-73.60,-73.66,-73.69,-73.72；
13C-NMR(101MHz,CHLOROFORM-D)146.4,146.3,146.3,146.2,146.2,146.1,145.2,145.1,145.0,145.0,143.3,143.2,143.0,143.0,142.9,142.7,142.6,142.4,142.3,142.1,142.0,141.9,141.5,139.2,138.6,138.2,137.9,137.8,137.6,137.4,137.4,137.2,137.2,137.0,123.0,129.9,129.7,129.6,129.4,129.3,129.2,128.9,128.8,128.7,128.6,128.4,128.1,126.0,125.8,125.7,125.6,125.5,125.4,123.24-113.57(J＝322Hz,CF3),122.8,122.7,122.1,122.0,121.8,121.7,121.6,115.6,115.4,45.7,45.5,45.4,45.3,45.2,45.1,45.0,44.9,44.7,44.6,29.0,28.9,12.2,12.1,12.0；
HRMS(APCI)calcd.for C60H54F18O18S6Cl-:[M+Cl]-m/z 1631.1041,found1631.1063.
VIb：
1H-NMR(400MHz,CHLOROFORM-D)7.28-7.42(m,3H),7.01-7.25(m,15H),4.13-4.21(m,6H),1.84-1.92(m,12H),0.75-0.77(m,18H)；
19F-NMR(376MHz,CHLOROFORM-D)-73.35,-73.41,-73.60,-73.69；
13C-NMR(101MHz,CHLOROFORM-D)146.4,146.4,146.3,146.2,145.1,145.0,144.9,144.8,144.8,142.9,142.7,142.6,142.3,142.1,142.1,142.0,141.8,141.7,141.7,139.0,138.8,138.6,138.3,138.1,137.9,137.8,137.6,137.4,129.9,129.7,129.6,129.6,129.5,129.4,129.2,129.1,129.0,128.9,128.8,128.7,128.5,128.4,128.3,128.2,128.2,128.1,125.9,125.7,125.6,125.5,123.3-113.7(J＝322Hz,CF3),123.2-113.7(JC,F＝322Hz,CF3),122.6,122.6,122.5,122.4,122.4,122.3,122.0,121.9,121.7,115.6,115.4,115.2,45.5,45.3,45.2,45.0,44.8,29.0,12.2,12.1,12.0；
HRMS(APCI)calcd.for C60H54F18O18S6Cl-:[M+Cl]-m/z 1631.1041,found1631.1063.
As is clear from the above, the compounds have the correct structures and are represented by the formula (VIa) and the formula (VIb), respectively.
The compound represented by the formula (VIIa) and the compound represented by the formula (VIIb) are prepared as follows:
Figure BDA0002140642030000161
a50 mL Schlenk flask was charged with 1.8mmol (1.6g) of a mixture of the compound of formula (VIIIa) and the compound of formula (VIIIb), 18mL of dichloromethane. After stirring well at room temperature, the system was placed in an ice-water bath and 16.2mmol (1.56mL) of boron tribromide was slowly added to the system using a 2.5mL syringe. After the addition was complete, the system was allowed to warm to room temperature and the reaction was continued for 12 h. After the reaction was completed, ice water was slowly added thereto to quench, the aqueous phase was extracted with ethyl acetate, and the organic phases were combined, washed with saturated brine and dried over anhydrous sodium sulfate. After the solvent was dried by spinning, recrystallization from methylene chloride-petroleum ether gave 1.4g of a mixture of the compound represented by the formula (VIIa) and the compound represented by the formula (VIIb) in a yield of 99%.
VIIb：
1H-NMR(400MHz,DMSO-D6)8.82-9.03(m,6H),6.75-7.42(m,14H),6.53-6.58(m,2H),6.21-6.24(m,2H),3.85-4.20(m,6H),1.68-2.03(m,12H),0.62-0.73(m,19H)；
13C-NMR(101MHz,DMSO-D6)152.5,152.4,152.4,152.2,152.2,152.1,146.3,146.2,146.2,146.1,145.4,145.3,145.2,145.1,136.5,136.4,136.3,131.5,131.4,127.6,127.5,127.4,127.3,127.1,127.0,126.9,124.6,124.4,124.3,123.5,123.3,123.3,123.2,123.1,123.0,122.4,122.3,122.2,122.2,114.2,113.9,101.8,43.9,43.4,42.8,42.6,42.4,42.2,29.0,28.9,28.6,28.4,28.3,28.1,12.7,12.7,12.6,12.6；
HRMS(APCI)calcd.for C54H61O6 +:[M+H]+m/z 805.4463,found 805.4460.
As can be seen from the above, the compound has a correct structure and is represented by formula VIIb.
The compound shown in the formula (VIIIa) and the compound shown in the formula (VIIIb) are prepared by the following steps:
Figure BDA0002140642030000171
into a 250mL three-necked flask was added 2.4mmol (2.2g) of Pd2(dba)3With 4.8mmol (3g) of 2,2 '-bisdiphenylphosphino-1, 1' -Binaphthyl (BINAP) and injected with 30mL of toluene previously bubbled with oxygen. The reaction was heated to reflux and reacted for 30 min. After cooling to room temperature, a mixture of 3mmol (5.4g) of the compound represented by the formula (Ixa) and the compound represented by the formula (Ixb), 108mmol (15mL) of triethylamine, 108mmol (4mL) of anhydrous formic acid and 30mL of o-xylene were added to the system. After stirring evenly at room temperature, the system is heated to 140 ℃ and reacted for 60 h. After the reaction, solvent spin-dry column chromatography (silica gel 100-200 mesh, eluent: petroleum ether/dichloromethane ═ 1.5/1) was performed to separate 1.76g of a mixture of the compound represented by formula (VIIIa) and the compound represented by formula (VIIIb), with a yield of 66%.
VIIIb：
1H-NMR(400MHz,CHLOROFORM-D)7.40-7.45(m,4H),7.30-7.36(m,2H),6.96-7.10(m,8H),6.63-6.68(m,2H),6.35(s,2H),4.01-4.32(m,6H),3.63-3.81(m,18H),1.79-2.05(m,12H),0.69-0.77(m,17H)；
13C-NMR(101MHz,CHLOROFORM-D)155.6,155.5,155.5,155.5,155.4,155.1,155.0,146.1,146.0,145.6,145.5,138.0,137.7,134.3,134.2,128.0,127.8,127.7,127.6,127.6,127.0,126.9,126.4,126.3,125.7,125.5,125.2,124.5,124.3,124.1,123.4,123.3,123.2,110.4,109.9,109.8,95.9,95.8,95.7,56.3,56.1,56.1,55.9,55.9,55.7,44.9,44.3,44.2,43.7,43.6,43.0,42.9,29.4,29.34,29.3,29.2,29.1,29.0,29.0,12.9,12.8,12.7；
HRMS(APCI)calcd.for C60H73O6 +:[M+H]+m/z 889.5402,found 889.5389
As is clear from the above, the compound has a correct structure and is represented by the formula (VIIIb).
The preparation of the mixture of the compound of formula (IXa) and the compound of formula (IXb) is as follows:
Figure BDA0002140642030000181
a1000 mL three-necked flask was charged with 6mmol (5.91g) of a mixture of the compound represented by the formula (Xa) and the compound represented by the formula (Xb), 300mL of methylene chloride and 108mmol (8.7mL) of pyridine, stirred at room temperature, and after stirring the mixture uniformly, the system was placed in an ice-water bath, and 72mmol (12mL) of trifluoromethanesulfonic anhydride was slowly added to the system using a 25mL constant pressure dropping funnel. After dropping, the system was heated to reflux and the reaction was continued for 12 h. After the reaction was completed, the reaction solution was quenched by slowly adding ice water, the aqueous phase was extracted with dichloromethane, and the combined organic phases were washed with saturated brine and dried over anhydrous sodium sulfate. The solvent spin-dry column chromatography (silica gel 100-200 mesh, eluent: petroleum ether/dichloromethane ═ 2.5/1) was performed to separate 7.5g of a mixture of the compound represented by the formula (IXa) and the compound represented by the formula (IXb), with a yield of 70%.
IXb：
1H-NMR(400MHz,CHLOROFORM-D)7.20-7.24(m,2H),7.13-7.17(m,2H),6.97-7.03(m,2H),6.64-6.73(m,4H),6.36-6.39(m,2H),4.43-4.65(m,6H),3.72-3.83(m,18H),1.67-1.85(m,12H),0.69-0.73(m,18H)；
19F-NMR(376MHz,CHLOROFORM-D)-73.41,-73.48,-73.84,-73.94,-74.00,-74.24,-74.37；
13C-NMR(101MHz,CHLOROFORM-D)156.8,156.7,156.4,156.4,156.2,155.8,155.7,147.1,147.0,146.9,146.6,145.9,145.8,145.7,145.5,145.4,145.4,145.3,145.3,145.2,138.8,138.8,138.6,138.6,138.5,138.4,138.3,137.5,137.4,131.7,130.7,130.6,130.6,130.5,129.6,129.5,129.5,128.8,128.6,128.5,128.2,127.1,127.0,126.9,125.4,125.3,113.9-123.6(J＝322Hz,CF3),123.0,123.0,123.0,122.0,121.8,121.8,121.6,121.6,114.6,114.4,114.3,114.2,104.0,103.7,103.6,103.4,95.0,55.9,55.8,55.6,37.6,37.4,37.2,37.1,36.9,36.8,36.7,36.5,36.4,36.3,28.8,28.7,12.2,12.1,12.0；
HRMS(APCI)calcd.for C66H67F18O24S6 +:[M+H]+m/z 1777.2054,found 1777.2046.
As is clear from the above, the above-mentioned compound has a correct structure and is represented by the formula (IXb).
The preparation method of the compound shown in the formula (Xa) and the compound shown in the formula (Xb) is as follows:
Figure BDA0002140642030000191
a500 mL three-necked flask was charged with 10mmol (9g) of the compound represented by the formula (XI), 60mmol (8.3g) of potassium carbonate and 300mL of acetone, heated to reflux, and reacted for 30 min. After cooling to room temperature, 30mmol (18.9mL) of methyl iodide was slowly added dropwise from a 60mL constant pressure dropping funnel, and after completion of the dropwise addition, the system was heated to reflux for 6 hours. After the reaction was complete, the solvent was spun dry, and the resulting solid was dissolved in ethyl acetate and filtered. The filtrate was subjected to spin-dry column chromatography (silica gel 200 to 300 mesh, eluent: dichloromethane/ethyl acetate 30/1) to give 6.8g of a mixture of the compound represented by the formula (Xa) and the compound represented by the formula (Xb), with a yield of 70%.
Xb：
1H-NMR(400MHz,DMSO-D6)8.58-8.64(m,2H),8.38-8.44(m,4H),6.82-6.84(m,2H),6.76-6.77(m,2H),6.68-6.69(m,2H),6.43(s,2H),6.23(s,2H),6.11(s,2H),4.27-4.40(m,6H),3.58-3.69(m,18H),1.58-1.60(m,12H),0.59-0.61(m,18H)；
13C-NMR(101MHz,DMSO-D6)155.2,155.2,155.1,154.8,154.7,152.7,152.6,152.4,152.3,125.9,125.8,125.7,125.6,125.5,125.5,125.4,124.4,124.3,124.2,124.1,123.2,123.2,123.1,123.1,123.0,122.2,122.2,122.1,122.0,122.0,121.9,101.8,98.7,96.4,55.9,55.5,34.7,34.6,28.4,28.2,28.1,12.2；
HRMS(APCI)calcd.for C60H71O12 -:[M-H]-m/z 983.4946,found 983.4954.
As is clear from the above, the above-mentioned compound has a correct structure and is represented by the formula (Xb).
Example 2: preparation of Compound Ib (corresponding to R in formula (I))1Ph; r2Is H; r3To Et)
The reaction formula is as follows:
Figure BDA0002140642030000201
a mixture of 0.1mmol (133.3mg) of the compound of formula (IVaa) and the compound of formula (IVba), 3mmol (113.5mg) of sodium borohydride and 2mL of absolute ethanol were added to a 10mL Schlenk tube, and the mixture was stirred at room temperature overnight. After the reaction is finished, saturated ammonium chloride solution is slowly added for quenching. The aqueous phase was extracted with ethyl acetate, and the organic phases were combined, washed with saturated brine and dried over anhydrous sodium sulfate. After the solvent was dried, the solid was dissolved in 10mL of dichloromethane and placed in a 25mL Schlenk flask, and 0.2mL of methanesulfonic acid was added and reacted at 0 ℃ for 0.2 h. After completion of the reaction, the reaction mixture was quenched with water, the aqueous phase was extracted with dichloromethane, and the combined organic phases were washed with saturated brine and dried over anhydrous sodium sulfate. And (3) performing spin-drying solvent column chromatography (silica gel 100-200 meshes, eluent: petroleum ether/dichloromethane: 1/1) to obtain a mixture of the compounds shown in the formula (Ib) with various configurations, wherein the total amount of the compounds is 45.0mg, and the yield is 36%. When separation is carried out by using a preparative thin-layer chromatography precast slab (the thickness of the coating is 0.9-1.1 mm, and petroleum ether/dichloromethane serving as a developing solvent is 2/1), the compound shown in the formula (Ib-1) and the compound shown in the formula (Ib-2) are obtained,
Figure BDA0002140642030000202
Figure BDA0002140642030000211
Ib-1：
1H-NMR(400MHz,CHLOROFORM-D)7.41-7.54(m,15H),6.96-7.01(m,15H),6.89(s,6H),6.80-6.82(m,6H),5.08(s,3H),4.74(s,3H),3.69(t,J＝6.4Hz,3H),3.31(t,J＝8.0Hz,3H),2.34-2.41(m,6H),1.41(t,J＝7.3Hz,9H),1.04-1.12(m,6H),0.74(t,J＝7.3Hz,9H)；
HRMS(APCI)calcd.for C96H85 +:[M+H]+m/z 1238.6679,found 1238.6655.
Ib-2
1H-NMR(400MHz,CHLOROFORM-D)7.49-7.53(m,4H),7.41-7.46(m,8H),7.32-7.36(m,3H),7.12-7.16(m,4H),7.03-7.09(m,6H),6.97-7.01(m,8H),6.93(s,2H),6.92(s,2H),6.89(s,1H),6.86(s,2H),6.79-6.80(m,2H),5.18(s,1H),5.08(s,2H),4.90(s,2H),4.69(s,1H),3.71(t,J＝6.4Hz,2H),3.31-3.38(m,4H),2.34-2.41(m,4H),2.06-2.13(m,2H),1.42(t,J＝7.1Hz,6H),1.14-1.20(m,6H),0.73-0.80(m,12H)；
HRMS(APCI)calcd.for C96H85 +:[M+H]+m/z 1238.6679,found 1238.6655.
as is clear from the above, the compound has a correct structure and is represented by the formula (Ib).
The preparation method of the compound shown in the formula (IVaa) and the compound shown in the formula (IVba) is as follows:
Figure BDA0002140642030000221
a50 mL Schlenk bottle was charged with 0.2mmol (172mg) of a mixture of the compound represented by the formula (Va) and the compound represented by the formula (Vb), and 2mL of tetrahydrofuran. After stirring well at room temperature, 7.8mL of phenyl Grignard reagent (1M in THF) was slowly added to the system using a 10mL syringe, and the reaction was continued at room temperature for 30 min. The system was then placed in a 70 ℃ oil bath and reacted for 24 h. After the reaction is finished, cooling to room temperature, slowly adding 4mL of 6M hydrochloric acid into the system, and heating to 70 ℃ again after the system is clear to react for 12 hours. After the reaction was completed, the aqueous phase was extracted with ethyl acetate, and the organic phases were combined, washed with a saturated sodium chloride solution and dried over anhydrous sodium sulfate. The compound represented by the formula (IVaa) and the compound represented by the formula (IVba) were separated by solvent spin-dry column chromatography (silica gel 100-200 mesh, eluent: dichloromethane/ethyl acetate 120/1) in a total of 215mg with a yield of 81%.
IVaa：
1H-NMR(400MHz,CHLOROFORM-D)7.30-7.92(m,37H),6.65-7.16(m,11H),4.20-4.39(m,6H),1.97-2.16(m,12H),0.68-0.90(m,18H)；
13C-NMR(101MHz,CHLOROFORM-D)198.7,198.6,198.5,198.0,197.7,147.3,147.2,147.1,146.9,146.5,146.2,146.1,144.8,144.6,144.3,144.23,144.15,143.2,138.2,138.1,138.0,138.0,137.6,137.3,137.1,136.73 136.5,136.4,135.6,133.7,133.6,133.4,133.3,133.3,133.2,130.4,130.20 129.1,129.0,128.8,128.6,128.5,128.5,128.4,127.5,127.2,126.6,125.0,124.8,124.7,123.0,48.1,47.9,47.8,47.7,47.6,47.5,29.5,29.4,12.8,12.7,12.7,12.6；
HRMS(APCI)calcd.for C96H84O6 -:[M]-m/z 1332.6273,found 1332.6276.
IVba：
1H-NMR(400MHz,CHLOROFORM-D)7.28-7.90(m,36H),6.66-7.18(m,12H),4.18-4.35(m,6H),2.08-2.20(m,12H),0.64-1.02(m,18H)；
13C-NMR(101MHz,CHLOROFORM-D)198.5,198.42 198.4,198.3,197.8,197.8,197.6,146.8,146.7,146.7,146.6,146.6,146.6,146.1,146.0,145.9,145.8,144.8,144.7,144.4,144.2,144.2,144.1,143.6,143.4,143.3,143.1,138.0,138.0,137.9,137.5,137.4,137.3,137.3,137.0,137.0,136.9,136.5,136.1,136.0,135.8,135.7,135.6,135.5,133.6,133.5,133.4,133.4,133.2,133.1,133.0,130.2,130.1,128.8,128.6,128.5,128.4,128.2,127.9,127.3,127.0,126.5,126.4,124.9,124.7,124.7,124.5,123.2,123.0,122.9,47.9,47.9,47.8,47.7,47.6,47.6,47.5,47.4,29.3,12.7；
HRMS(APCI)calcd.for C96H84O6 -:[M]-m/z 1332.6273,found 1332.6276.
As is clear from the above, the above compounds have the correct structures and are represented by formula (IVaa) and formula (IVba), respectively.
The compound represented by formula (Va) and the compound represented by formula (Vb) are prepared as follows:
Figure BDA0002140642030000231
a50 mL Schlenk flask was charged with 1mmol (1.6g) of a mixture of the compound of formula (VIa) and the compound of formula (VIb), 0.9mmol (1.04g) of palladium tetrakistriphenylphosphine, 7.5mmol (881mg) of zinc cyanide and 10mL of DMF. The reaction system was heated to 140 ℃ for 1 d. After the reaction was complete, it was quenched with saturated sodium bicarbonate solution and the aqueous phase was extracted with ethyl acetate, the remaining cyanide was washed with 5% sodium hypochlorite solution for oxidation. The organic phases were combined, washed with saturated sodium chloride solution and dried over anhydrous sodium sulfate. The solvent spin-dry column chromatography (silica gel 100-200 mesh, eluent: dichloromethane/ethyl acetate 100/1) was performed to obtain a total of 720mg of the compound of formula (Va) and formula (Vb), with a yield of 84%.
Va：
1H-NMR(400MHz,CHLOROFORM-D)7.29-7.90(m,15H),7.00-7.22(m,3H),4.21-4.43(m,6H),1.94-2.11(m,12H),0.81-0.88(m,18H)；
13C-NMR(101MHz,CHLOROFORM-D)154.6,152.8,151.6,150.9,150.1,148.7,148.4,148.3,148.2,148.0,147.9,147.8,147.7,147.6,147.3,147.1,147.1,146.8,146.6,146.4,146.3,146.3,143.4,143.0,142.6,141.6,137.1,134.0,133.8,133.8,133.7,133.6,133.5,129.7,129.6,129.6,129.5,129.4,129.3,129.2,128.9,128.9,128.8,128.6,125.9,125.6,123.8,123.7,123.6,123.6,123.5,123.43,123.32,121.9,121.9,117.7,117.6,117.5,117.4,117.3,117.12 115.8,115.6,115.4,112.8,112.5,112.4,112.4,112.3,112.2,111.9,111.8,111.7,50.8,50.7,50.5,50.4,50.4,50.2,29.4,29.4,29.2,29.0,28.9,28.8,12.4,12.3,12.1；
HRMS(APCI)calcd.for C60H55N6 +:[M+H]+m/z 859.4483,found 859.4471.
Vb：
1H-NMR(400MHz,CHLOROFORM-D)7.87-7.91(m,2H),7.58-7.63(m,4H),7.28-7.45(m,8H),7.14-7.23(m,4H),4.25-4.41(m,6H),1.96-2.10(m,12H),0.81-0.86(m,18H)；
13C-NMR(101MHz,CHLOROFORM-D)154.1,154.0,153.8,153.4,153.3,152.6,152.3,152.0,151.5,151.4,149.5,149.4,148.9,148.6,147.8,147.5,146.8,146.5,146.4,143.3,143.2,143.1,142.8,142.2,142.0,142.0,141.9,141.8,141.7,137.2,133.9,133.8,133.7,123.0,129.9,129.8,129.8,129.7,129.7,129.6,129.4,129.2,129.1,129.1,129.0,128.9,128.8,125.7,125.6,123.6,123.4,123.4,121.7,121.6,121.4,121.3,117.6,117.5,117.5,117.4,117.2,116.0,115.9,115.8,115.8,115.7,115.6,115.6,115.5,112.6,112.6,112.4,112.4,112.3,112.2,112.2,112.2,112.0,112.0,111.9,111.8,50.7,50.6,50.5,50.4,50.4,50.3,50.2,29.4,29.2,29.0,28.8,12.4,12.3,12.1；
HRMS(APCI)calcd.for C60H55N6 +:[M+H]+m/z 859.4483,found 859.4471.
As is clear from the above, the compounds have correct structures and are represented by the formula (Va) and the formula (Vb).
Example 3: preparation of Compound Ic (corresponding to R in formula (I))1Is 3, 5-dimethylphenyl; r2Is H; r3To Et)
The reaction formula is as follows:
Figure BDA0002140642030000251
the preparation method comprises the following steps:
a mixture of 0.1mmol (150.3mg) of the compound represented by the formula (IVab) and the compound represented by the formula (IVbb), 3mmol (113.5mg) of sodium borohydride and 2mL of absolute ethanol were added to a 10mL Schlenk's tube, and the mixture was stirred at room temperature overnight. After the reaction is finished, saturated ammonium chloride solution is slowly added for quenching. The aqueous phase was extracted with ethyl acetate, and the organic phases were combined, washed with saturated brine and dried over anhydrous sodium sulfate. After the solvent was dried, the solid was dissolved in 10mL of dichloromethane and placed in a 25mL Schlenk flask, and 0.2mL of methanesulfonic acid was added and reacted at 0 ℃ for 0.2 h. After completion of the reaction, the reaction mixture was quenched with water, the aqueous phase was extracted with dichloromethane, and the combined organic phases were washed with saturated brine and dried over anhydrous sodium sulfate. The compound represented by the formula (Ic) with various configurations was isolated by spin-drying solvent column chromatography (silica gel 100-200 mesh, eluent: petroleum ether/dichloromethane 5/1) to obtain 36.7mg of a mixture of compounds represented by the formula (Ic), with a yield of 26%. When separation is carried out by using a preparative thin-layer chromatography precast slab (the thickness of the coating is 0.9-1.1 mm, and the developing solvent petroleum ether/dichloromethane is 2/1), one of the configurations of Ic-1 (Ar is 3, 5-dimethylphenyl in the formula (Ic-1)) can be obtained,
Figure BDA0002140642030000252
Ic-1
1H-NMR (400MHz, CHLOROFORM-D)7.08(s,6H),7.00(s,3H),6.94(s,6H),6.90(s,6H),6.60(s,3H),6.43(s,6H),4.98(s,3H),4.63(s,3H),3.67(t, J ═ 6.2Hz,3H),3.28(t, J ═ 8.0Hz,3H),2.37(s,18H),2.31-2.40(m,6H),2.04(s,18H),1.40(t, J ═ 7.1Hz,9H),1.11-1.18(m,6H),0.75(t, J ═ 7.3Hz, 9H); (see fig. 3)
13C-NMR (101MHz, CHLOROFORM-D)144.9,141.1,140.0,139.4,137.5,137.2,137.0,136.2,129.9,128.8,127.2,127.1,125.0,123.0,51.1,51.0,50.9,43.8,29.8,21.3,21.2,19.8,13.5, 12.9; (see fig. 4)
HRMS(APCI)calcd.for C108H107 -:[M-H]-m/z 1404.8412,found 1404.8446.
As is clear from the above, the compound has a correct structure and is represented by the formula (Ic).
The compounds of formula (IVab) and (IVbb) are prepared as follows:
Figure BDA0002140642030000261
a25 mL Schlenk flask was charged with 14.04mmol (341mg) of magnesium metal, 10mL of tetrahydrofuran and 11.7mmol (1.6mL) of 3, 5-dimethylbromobenzene, stirred at room temperature for 1h, and allowed to stand for further use. A50 mL Schlenk flask was charged with 0.3mmol (258mg) of a mixture of the compound represented by the formula (Va) and the compound represented by the formula (Vb), and 2mL of tetrahydrofuran. After stirring uniformly at room temperature, the new Grignard reagent was slowly added to the system using a 20mL syringe, and the reaction was continued at room temperature for 30 min. The system was then placed in a 70 ℃ oil bath and reacted for 24 h. After the reaction is finished, cooling to room temperature, slowly adding 4mL of 6M hydrochloric acid into the system, and heating to 70 ℃ again after the system is clear to react for 12 hours. After the reaction was completed, the aqueous phase was extracted with ethyl acetate, and the organic phases were combined, washed with a saturated sodium chloride solution and dried over anhydrous sodium sulfate. The compound represented by the formula (IVab) and the compound represented by the formula (IVbb) were separated by solvent spin-dry column chromatography (silica gel 100-200 mesh, eluent: dichloromethane/ethyl acetate: 100/1) in a total of 326mg, and the yield was 57%.
IVab：
1H-NMR(400MHz,CHLOROFORM-D)7.28-7.86(m,12H),6.60-7.24(m,24H),4.18-4.41(m,6H),1.96-2.43(m,48H),0.66-0.97(m,18H)；
13C-NMR(101MHz,CHLOROFORM-D)199.25,199.23,199.17,198.98,198.33,147.04,146.99,146.71,146.15,146.03,145.86,144.95,144.28,144.15,144.13,144.04,143.23,138.42,138.36,138.28,138.18,138.14,138.04,137.93,137.83,137.74,137.54,137.39,137.09,137.08,136.50,135.99,135.45,135.27,135.20,135.14,134.89,134.80,128.92,128.80,128.20,128.11,127.89,127.60,127.56,127.51,127.11,126.41,125.35,125.01,124.89,124.81,123.50,48.15,47.67,47.44,47.28,29.59,29.50,29.45,29.34,29.28,21.26,13.15,12.99,12.92,12.81,12.74；
HRMS(APCI)calcd.for C108H108O6Cl-:[M+Cl]-m/z 1536.7873,found 1536.7855.
IVbb：
1H-NMR(400MHz,CHLOROFORM-D)7.30-7.83(m,8H),6.56-7.24(m,28H),4.08-4.34(m,6H),2.05-2.40(m,48H),0.69-0.99(m,18H)；
13C-NMR(101MHz,CHLOROFORM-D)199.2,199.1,199.0,199.0,198.7,198.7,198.6,198.4,198.4,198.4,198.3,198.3,146.8,146.5,146.3,146.2,146.0,145.8,145.7,145.6,145.6,145.5,145.3,144.8,144.7,144.6,144.4,144.2,144.0,143.9,143.8,143.7,143.4,143.3,143.2,143.0,142.9,142.5,138.2,138.2,138.1,138.0,138.0,137.9,137.8,137.7,137.6,137.6,137.5,137.4,137.0,136.9,136.7,136.6,136.3,136.1,136.1,136.0,135.6,135.3,135.2,135.2,135.0,135.0,134.9,134.8,134.7,128.7,128.6,128.4,128.3,128.1,128.1,127.9,127.8,127.5,127.4,127.0,126.9,126.9,126.64 126.4,126.3,126.2,126.1,126.0,125.2,124.9,124.7,124.6,123.7,123.4,123.4,123.3,123.2,122.3,48.0,47.9,47.8,47.6,47.6,47.5,47.4,47.4,47.3,47.2,29.5,29.4,29.3,29.0,21.1,12.9,12.9,12.7,12.6,12.5；
HRMS(APCI)calcd.for C108H108O6Cl-:[M+Cl]-m/z 1536.7873,found 1536.7855.
As is clear from the above, the compounds have the correct structures and are represented by the formula (IVab) and the formula (IVbb), respectively.
Example 4 Selective Inclusion of chloroform by Compounds of the macrocyclic formula (Ib-1)
The annulated [12] arene compound provided by the invention can identify solvent molecules in a solid phase.
When 2mg of the compound represented by the above formula (Ib-1) was dissolved in 0.5mL of chloroform and acetonitrile was slowly diffused therein by the vapor phase diffusion method, crystals were obtained as transparent masses, and the structure diagram is shown in FIG. 5. Single crystal X-ray diffraction experiments show that a 1:2 complex structure is formed between a guest molecule chloroform and a macrocyclic host. A chloroform molecule is entirely enclosed by the barrel-shaped cavity of the body. In addition, the molecule is also brought close to another chloroform molecule by intermolecular forces and the chloroform molecule is pulled to the edge of the barrel-shaped cavity. The main forces for maintaining the structure are the non-classical hydrogen bond of chlorine atom and hydrogen atom on the main body, the lp of chlorine atom to aromatic ring…Pi interactions and dipole-dipole interactions between chloroform molecules.
In the description herein, references to the description of the term "one embodiment," "some embodiments," "an example," "a specific example," or "some examples," etc., mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above are not necessarily intended to refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples. Furthermore, various embodiments or examples and features of different embodiments or examples described in this specification can be combined and combined by one skilled in the art without contradiction.
Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention, and that variations, modifications, substitutions and alterations can be made to the above embodiments by those of ordinary skill in the art within the scope of the present invention.

Claims (17)

1. A compound of formula (I) or a stereoisomer thereof,
Figure FDA0002579972100000011
wherein the content of the first and second substances,
R1and R2Each independently is a hydrogen atom, a methyl group, an ethyl group, a n-propyl group, a n-butyl group, a phenyl group or an optionally substituted phenyl group;
R3is ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, benzyl, p-methylbenzyl, o-methylbenzyl or m-methylbenzyl.
2. The compound of claim 1, wherein the optionally substituted phenyl is 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 2-isopropylphenyl, 3-isopropylphenyl, 4-isopropylphenyl, 3, 4-dimethylphenyl, 3, 5-dimethylphenyl, 3, 6-dimethylphenyl, 2, 3-dimethylphenyl, 2, 4-dimethylphenyl, 2, 5-dimethylphenyl, 2, 6-dimethylphenyl, 3, 4-diethylphenyl, 3, 5-diethylphenyl, 3, 6-diethylphenyl, 2, 3-diethylphenyl, 2, 4-diethylphenyl, 2-isopropylphenyl, 3, 4-dimethylphenyl, 3-dimethylphenyl, or 2-isopropylphenyl, 2, 5-diethylphenyl, 2, 6-diethylphenyl or 3,4, 5-trimethylphenyl.
3. The compound of claim 1, having the structure of one of:
Figure FDA0002579972100000021
4. a process for preparing a compound according to any one of claims 1 to 3, comprising:
contacting a first raw material or a second raw material with an acid to obtain a compound represented by formula (I), wherein the first raw material comprises at least one of a compound represented by formula (IIa) and a compound represented by formula (IIb), and the second raw material comprises at least one of a compound represented by formula (IIIa) and a compound represented by formula (IIIb),
Figure FDA0002579972100000022
Figure FDA0002579972100000031
wherein R is1And R3As defined in claim 1 or 2.
5. The method according to claim 4, wherein the acid is selected from at least one of polyphosphoric acid, hydrochloric acid, sulfuric acid, trifluoromethanesulfonic anhydride, trimethylsilylsulfonate, methanesulfonic acid, p-toluenesulfonic acid, perfluorosulfonic acid resin, and scandium trifluoromethanesulfonate.
6. The method of claim 4, wherein the contacting is performed in a first solvent selected from at least one of benzene, toluene, trifluorotoluene, chlorobenzene, fluorobenzene, nitrobenzene, bromobenzene, dichloromethane, 1, 2-dichloroethane, 1,2, 2-tetrachloroethane, and chloroform;
optionally, the contacting is carried out at-40 to 150 ℃ for 0.1 to 48 hours;
optionally, the dosage ratio of the first raw material to the acid is 0.01-1 mmol: 0.01-100 mmol, and the dosage ratio of the second raw material to the acid is 0.01-1 mmol: 0.01-10 mL.
7. The method according to claim 4, wherein the compound of formula (IIa) is prepared by subjecting the compound of formula (VIa) to a first cross-coupling reaction under the action of a first metal catalyst, and the compound of formula (IIb) is prepared by subjecting the compound of formula (VIb) to a first cross-coupling reaction under the action of a first metal catalyst,
Figure FDA0002579972100000032
optionally, the compound shown in the formula (IIIa) is prepared by carrying out a reduction reaction on the compound shown in the formula (IVa) under the action of a reducing agent, the compound shown in the formula (IIIb) is prepared by carrying out a reduction reaction on the compound shown in the formula (IVb) under the action of a reducing agent,
Figure FDA0002579972100000041
optionally, the compound represented by the formula (IVa) is prepared by subjecting the compound represented by the formula (Va) to addition reaction with a Grignard reagent, the compound represented by the formula (IVb) is prepared by subjecting the compound represented by the formula (Vb) to addition reaction with a Grignard reagent,
Figure FDA0002579972100000042
optionally, the compound shown in the formula (Va) is prepared by subjecting the compound shown in the formula (VIa) to a second cross-coupling reaction under the action of a second metal catalyst, and the compound shown in the formula (Vb) is prepared by subjecting the compound shown in the formula (VIb) to a second cross-coupling reaction under the action of a second metal catalyst;
optionally, the compound represented by the formula (VIa) is prepared by subjecting the compound represented by the formula (VIIa) to a first trifluoromethanesulfonylation reaction, the compound represented by the formula (VIb) is prepared by subjecting the compound represented by the formula (VIIb) to a first trifluoromethanesulfonylation reaction,
Figure FDA0002579972100000043
optionally, the compound shown in the formula (VIIa) is prepared by reacting the compound shown in the formula (VIIIa) with acid and hydrolyzing, the compound shown in the formula (VIIb) is prepared by reacting the compound shown in the formula (VIIIb) with acid and hydrolyzing,
Figure FDA0002579972100000051
optionally, the compound shown in the formula (VIIIa) is prepared by subjecting the compound shown in the formula (IXa) to catalytic coupling reaction, the compound shown in the formula (VIIIb) is prepared by subjecting the compound shown in the formula (IXb) to catalytic coupling reaction,
Figure FDA0002579972100000052
optionally, the compound represented by the formula (IXa) is prepared by subjecting the compound represented by the formula (Xa) to a second trifluoromethanesulfonylation reaction, the compound represented by the formula (IXb) is prepared by subjecting the compound represented by the formula (Xb) to a second trifluoromethanesulfonylation reaction,
Figure FDA0002579972100000053
optionally, the compound shown in the formula (Xa) and the compound shown in the formula (Xb) are prepared by subjecting the compound shown in the formula (XI) to selective methylation reaction,
Figure FDA0002579972100000061
8. the method of claim 7, wherein the first metal catalyst is selected from at least one of palladium acetate, tetrakistriphenylphosphine palladium, tris (dibenzylideneacetone) dipalladium, palladium chloride, or [1, 1' -bis (diphenylphosphino) ferrocene ] palladium dichloride;
optionally, the first cross-coupling reaction is carried out in a second solvent selected from at least one of N, N-dimethylformamide, N-dimethylaniline, N-dimethylacetamide, N-methylpyrrolidone, tetrahydrofuran, 1, 4-dioxane, water, and dimethylsulfoxide;
optionally, the first cross-coupling reaction is carried out under the action of an additive and an alkenylation reagent, the additive being selected from at least one of potassium carbonate, cesium carbonate, lithium carbonate, sodium chloride and lithium chloride; the alkenylation reagent is selected from at least one of vinyl magnesium bromide, isopropenyl magnesium bromide, tributyl vinyl ene, tributyl isopropenyl ene, isopropenyl boronic acid pinacol ester and vinyl boronic acid pinacol ester;
optionally, the first cross-coupling reaction is carried out at 25-140 ℃ for 6-36 h.
9. The method of claim 7, wherein the reducing agent is selected from at least one of lithium aluminum hydride, sodium borohydride, lithium borohydride, hydrogen gas, red aluminum, diisobutyl aluminum hydride, and borane dimethylsulfide;
optionally, the reduction reaction is carried out in a third solvent selected from at least one of tetrahydrofuran, 1, 4-dioxane, ethanol, and methanol;
optionally, the reduction reaction is carried out for 1-24 hours at-78-80 ℃.
10. The method of claim 7, wherein the Grignard reagent is selected from the group consisting of phenylmagnesium bromide, 2-methylphenylmagnesium bromide, 3-methylphenylmagnesium bromide, 4-methylphenylmagnesium bromide, 2-ethylphenylmagnesium bromide, 3-ethylphenylmagnesium bromide, 4-ethylphenylmagnesium bromide, 2-isopropylphenylmagnesium bromide, 3-isopropylphenylmagnesium bromide, 4-isopropylphenylmagnesium bromide, 3, 4-dimethylphenylmagnesium bromide, 3, 5-dimethylphenylmagnesium bromide, 3, 6-dimethylphenylmagnesium bromide, 2, 3-dimethylphenylmagnesium bromide, 2, 4-dimethylphenylmagnesium bromide, 2, 5-dimethylphenylmagnesium bromide, 2, 6-dimethylphenylmagnesium bromide, 3, 4-diethylphenylmagnesium bromide, At least one of 3, 5-diethylphenylmagnesium bromide, 3, 6-diethylphenylmagnesium bromide, 2, 3-diethylphenylmagnesium bromide, 2, 4-diethylphenylmagnesium bromide, 2, 5-diethylphenylmagnesium bromide, 2, 6-diethylphenylmagnesium bromide and 3,4, 5-trimethylphenylmagnesium bromide;
optionally, the addition reaction is carried out in a fourth solvent selected from at least one of tetrahydrofuran and 1, 4-dioxane;
optionally, the addition reaction is carried out at-78-70 ℃ for 12-24 h.
11. The method of claim 7, wherein the second metal catalyst is selected from at least one of palladium acetate, tetrakistriphenylphosphine palladium, tris (dibenzylideneacetone) dipalladium, palladium chloride, and [1, 1' -bis (diphenylphosphino) ferrocene ] palladium dichloride;
optionally, the second cross-coupling reaction is carried out in a fifth solvent selected from at least one of N, N-dimethylformamide, N-dimethylaniline, N-dimethylacetamide, N-methylpyrrolidone, and dimethylsulfoxide;
optionally, the second cross-coupling reaction is carried out at 80-150 ℃ for 12-48 h.
12. The process of claim 7, wherein the first trifluoromethanesulfonylation is carried out with the aid of a base selected from at least one of pyridine, triethylamine, diethylamine, N-diisopropylethylamine, 2, 6-lutidine and potassium carbonate;
optionally, the first trifluoromethanesulfonylation reaction is carried out in a sixth solvent selected from at least one of dichloromethane, trichloromethane, 1, 2-dichloroethane, toluene and benzene;
optionally, the first trifluoromethanesulfonylation reaction is completed at-78-45 ℃ for 3-24 h.
13. The method of claim 7, wherein the acid comprises at least one of boron trichloride, boron tribromide, boron triiodide, and hydrobromic acid;
optionally, the reacting with an acid and hydrolyzing are performed in a seventh solvent selected from at least one of dichloromethane, trichloromethane and 1, 2-dichloroethane;
optionally, the reaction with acid and hydrolysis are carried out at-20 to 45 ℃ for 6 to 24 hours.
14. The method according to claim 7, wherein the metal catalyst used in the catalytic coupling reaction is selected from at least one of palladium acetate, tetratriphenylphosphine palladium, palladium on carbon, tris (dibenzylideneacetone) dipalladium, palladium chloride and [1, 1' -bis (diphenylphosphino) ferrocene ] palladium dichloride;
optionally, the ligand used in the catalytic coupling reaction is at least one selected from the group consisting of tetrakistriphenylphosphine, 1 ' -binaphthyl-2, 2 ' -bisdiphenylphosphine, 1, 3-bis (diphenylphosphino) propane, and 1,1 ' -bis (diphenylphosphino) ferrocene;
optionally, the hydrogen source used in the catalytic coupling reaction is at least one selected from formic acid, ammonium acetate and triethylhydrosilicon;
optionally, the catalytic coupling reaction is carried out in an eighth solvent selected from at least one of N, N-dimethylformamide, N-dimethylaniline, N-dimethylacetamide, N-methylpyrrolidone, dimethylsulfoxide, toluene, xylene, and mesitylene;
optionally, the catalytic coupling reaction is carried out at 80-150 ℃ for 12-72 h.
15. The process of claim 7, wherein the second triflation reaction is carried out under the action of a base selected from at least one of pyridine, triethylamine, diethylamine, N-diisopropylethylamine, 2, 6-lutidine and potassium carbonate;
optionally, the second trifluoromethanesulfonylation reaction is carried out in a ninth solvent selected from at least one of dichloromethane, chloroform, 1, 2-dichloroethane, toluene, and benzene;
optionally, the second trifluoromethanesulfonylation reaction is completed at-78-45 ℃ for 8-36 h.
16. The process according to claim 7, characterized in that the selective methylation reaction is carried out under the action of a base selected from at least one of sodium carbonate, potassium carbonate, cesium carbonate and cesium fluoride;
optionally, the methylating agent employed in the selective methylation reaction is selected from at least one of methyl iodide, dimethyl sulfate and dimethyl carbonate;
optionally, the selective methylation reaction is carried out in a tenth solvent selected from at least one of dichloromethane, trichloromethane, 1, 2-dichloroethane, acetone, N-dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, and 1, 4-dioxane;
optionally, the selective methylation reaction is carried out at 25-100 ℃ for 1-12 h.
17. Use of a compound according to any one of claims 1 to 3 for the selective inclusion of organic molecules to identify and selectively include organic molecules from a mixed solution comprising 1, 2-dichloroethane, methanol, chloroform, ethanol and acetonitrile.
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