Calix furan macrocyclic compound as well as preparation method, single crystal and identification application thereof

Abstract

The invention relates to a novel calix furan macrocyclic compound, a preparation method thereof, a single crystal and identification application. The cup furan macrocyclic compound provided by the invention has a ring structure as shown in a general formula (I), and n is an integer from 3 to 8, preferably an integer from 4 to 6, and more preferably 4; r1 and R2 independently represent hydrogen, a halogen, a cyano group, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C1-C6 alkylthio group, or a C6-C12 aryl group. In addition, the calix furan macrocyclic compound provided by the invention can specifically recognize methanesulfonic acid. # imgabs0 #

Description

Technical Field

[0001] The invention belongs to the technical field of organic chemical synthesis, and specifically relates to a new calixfuran macrocyclic compound and a preparation method and a single crystal thereof, and application in molecular recognition. Background Art

[0002] The host-guest interaction between macrocyclic molecules and small molecules or anions and cations is a common interaction in supramolecular chemistry and is ubiquitous in chemical and life systems. This interaction usually includes the recognition and binding between macrocyclic molecules (also called hosts) and specific guest molecules or ions (such as acids or metal ions). This recognition and binding is achieved through a variety of mechanisms, including but not limited to electrostatic interactions, hydrogen bonds, π-π stacking or hydrophobic interactions.

[0003] However, the macrocyclic molecules synthesized by the prior art generally have the problem of low yield or strict reaction conditions. Therefore, people have been trying to synthesize various new macrocyclic molecules with specific functions such as specific selectivity, especially macrocyclic molecules that can have specific recognition effects with acids. Summary of the invention

[0004] In view of this, in a first aspect, the present invention provides a calixfuran macrocyclic compound having a ring structure of the general formula (I):

[0005]

[0006] wherein n is an integer of 3-8, preferably an integer of 4-6, more preferably 4;

[0007] R1 and R2 independently represent hydrogen, halogen, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio or C6-C 12 Aryl.

[0008] In a second aspect, the present invention also provides a method for preparing a calixfuran macrocyclic compound having a ring structure of the general formula (I), comprising the following steps: reacting furan with a compound of the formula (a) in a solvent in the presence of an acid catalyst at a temperature of -10 to 40°C.

[0009]

[0010] wherein R1 and R2 are as defined above,

[0011] The acid catalyst is selected from hydrochloric acid, sulfuric acid and hydrobromic acid, preferably concentrated sulfuric acid.

[0012] In the present invention, the solvent may be any organic solvent inert to the reaction of the present invention, such as dichloromethane, chloroform, carbon tetrachloride, tetrachloroethane, toluene, trimethylbenzene, chlorobenzene, dichlorobenzene, tetrahydrofuran, dioxane and mixtures thereof, preferably dioxane.

[0013] Since the calixfuran macrocyclic compound of the present invention has a cavity structure of a specific size, it can be used to identify specific acid molecules (such as methanesulfonic acid MSA). BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 is the hydrogen spectrum of C4TP prepared in Example 1 of the present invention;

[0015] Figure 2 is the mass spectrum of C4TP prepared by Example 1 of the present invention;

[0016] Figure 3 is the crystal structure of C4TP prepared in Example 1 of the present invention;

[0017] Figure 4 The figure shows the comparison of UV-visible absorption spectra of the C4TP solution prepared in Example 1 of the present invention after adding different acids. DETAILED DESCRIPTION

[0018] In the present invention, unless otherwise stated, all operations are carried out at room temperature (25° C.) and normal pressure (101 KPa).

[0019] The inventors found in their research that the calixfuran macrocyclic compound of the present invention has a cavity structure of a specific size, which can be used to identify specific acid molecules (such as methanesulfonic acid MSA). In addition, the calixfuran macrocyclic compound can be prepared in a moderate yield and under mild reaction conditions by the method of the present invention.

[0020] Therefore, in a first aspect, the present invention provides a calixfuran macrocyclic compound having a ring structure of the general formula (I):

[0021]

[0022] wherein n is an integer of 3-8, preferably an integer of 4-6, more preferably 4 and 6;

[0023] R1 and R2 independently represent hydrogen, halogen, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio or C6-C 12 Aryl;

[0024] Preferably, the halogen is selected from fluorine, chlorine, bromine and iodine.

[0025] In a preferred embodiment of the present invention, n is 4 or 6, more preferably 4.

[0026] In a preferred embodiment of the present invention, R1 and R2 independently represent hydrogen, halogen, C1-C6 alkyl or C6-C 12 Aryl.

[0027] In a preferred embodiment of the present invention, R1 and R2 independently of one another represent hydrogen.

[0028] In a preferred embodiment of the present invention, the calixfuran macrocyclic compound of the present invention has the following structure (i.e., n=4 in the general formula (I) and R1 and R2 independently represent hydrogen, also referred to herein as "C4TP"):

[0029]

[0030] In a second aspect, the present invention also provides a method for preparing a calixfuran macrocyclic compound having a ring structure of the general formula (I), comprising the following steps: reacting furan with a compound of the formula (a) in a solvent in the presence of an acid catalyst at a temperature of -10 to 40°C.

[0031]

[0032] wherein R1 and R2 are as defined above,

[0033] The acid catalyst is selected from hydrochloric acid, sulfuric acid and hydrobromic acid, preferably concentrated sulfuric acid.

[0034] In the present invention, the term "concentrated sulfuric acid" refers to a mixture of sulfuric acid (H2SO4) and water in which the volume percentage of sulfuric acid is greater than 60%, preferably greater than 80%, more preferably greater than 90%, and especially 90% to 91%.

[0035] In the present invention, the solvent is selected from various organic solvents inert to the reaction of the present invention, such as dichloromethane, chloroform, carbon tetrachloride, tetrachloroethane, toluene, trimethylbenzene, chlorobenzene, dichlorobenzene, tetrahydrofuran, dioxane and mixtures thereof, preferably dioxane.

[0036] In a preferred embodiment of the present invention, the molar ratio of furan to the compound of formula (a) may be 1:(0.8-1.2), preferably 1:(0.9-1.1), and more preferably 1:1.

[0037] In a preferred embodiment of the present invention, the concentration of the compound of formula (a) in the solvent may be (0.1-1.0) mmol / mL, preferably (0.2-0.8) mmol / mL, and more preferably (0.25-0.4) mmol / mL.

[0038] In a preferred embodiment of the present invention, the molar ratio of the compound of formula (a) to the acid catalyst may be 1:(2-6), preferably 1:(3-5), and more preferably 1:(4-4.5).

[0039] In a preferred embodiment of the present invention, the reaction time may be 4 to 24 hours, preferably 5 to 15 hours, more preferably 8 to 13 hours.

[0040] In a preferred embodiment of the present invention, when concentrated sulfuric acid (e.g., a concentration of 70-95% by volume) is used as an acid catalyst, in order to prevent the reaction temperature from being too high during the addition of the acid catalyst, the temperature can be set to less than 5° C., preferably 0° C., when the acid catalyst is added. Optionally, after the acid catalyst is added, the temperature is adjusted to the reaction temperature (e.g., room temperature) to carry out the reaction.

[0041] In a preferred embodiment of the present invention, the reaction temperature may be -5 to 35°C, preferably 15 to 30°C.

[0042] In a preferred embodiment of the present invention, after the reaction is completed, post-treatment can be performed in the following manner: first, the reaction mixture is poured into water, and then the precipitated solid is washed with an appropriate amount of a mixture of water and / or methanol (preferably a mixture of water and methanol in a volume ratio of 1:(0.5-2)). Finally, the obtained solid is further purified by a purification method known in the art, such as purification by silica gel column chromatography (gradient elution, such as dichloromethane to ethyl acetate).

[0043] The various embodiments described herein can be combined with each other. Combinations that violate the laws of nature and combinations that are excluded by a person skilled in the art based on his / her expertise are not included.

[0044] Hereinafter, the present invention will be described in more detail with reference to the following examples. These embodiments disclosed below are for illustrative purposes only and are not intended to limit the present invention. Those skilled in the art may make various modifications, additions and substitutions to the embodiments of the present invention without departing from the scope and spirit of the present invention.

[0045] 1. Preparation Example

[0046] Example 1

[0047] A solution of furan (0.68 g, 10 mmol) and tetrahydropyrone (1 g, 10 mmol) in 1,4-dioxane (30 mL) was added to a 100 mL round-bottom flask, cooled to 0 ° C, and 90.5% sulfuric acid (2.5 mL, 41.8 mmol) was added dropwise. Stirred at room temperature for 12 h, the solution turned purple-red. After the reaction was completed, it was poured into water (50 mL) to precipitate a light yellow solid, which was washed with water (20 mL) and methanol (20 mL). The obtained solid was further purified by silica gel column chromatography (dichloromethane to ethyl acetate) to obtain a white solid product C4TP with a yield of 20%.

[0048]

[0049] C4TP 1 H NMR (400MHz, CDCl3, 298K): δ = 5.93 (s, 8H), 3.66 (t, J

[0050] =28.5Hz,16H),2.15(t,J=28.5Hz,16H).HRMS(MALDI):calcd(%)for C 36 H 40 8Na + :623.2616,found[M+Na] + :623.3363.

[0051] 2. Crystal Test

[0052] 1. Crystal Preparation

[0053] The solid C4TP (5 mg) prepared in Example 1 was dissolved in a mixture of dichloromethane and methanol (3 mL and 2 mL) at room temperature, and the solvent was slowly evaporated to precipitate light yellow block crystals.

[0054] 2. Crystal test

[0055] Testing instrument: Bruker APEX-IICCD single crystal diffractometer

[0056] 2.1 Single crystal analysis was performed on the C4TP crystal prepared by the above method, and the single crystal data of the test are shown in Table 1 below.

[0057] Table 1

[0058]

[0059]

[0060] Therefore, the calixfuran macrocyclic compound having a ring structure of the general formula (I) of the present invention (where n=4, R1 and R2 are both hydrogen) belongs to the triclinic crystal form -P-1, C2 axis symmetry, wherein three furans face upward, one furan faces downward, tetrahydropyran is in a chair conformation, and the cavity size is about

[0061] 3. UV-visible absorption spectrum test

[0062] 1. Sample Preparation

[0063] The compound C4TP (6 mg) prepared in Example 1 was dissolved in dichloromethane (100 mL). Four portions, each 5 mL, were taken. The first portion was the reference group. 0.1 mL of hydrochloric acid (HCl), 0.1 mL of nitric acid (HNO3), and 0.1 mL of methanesulfonic acid (MSA) were added to the second to fourth portions, respectively. The UV-visible absorption spectrum was tested at room temperature. Figure 4 shown.

[0064] 2. Sample testing

[0065] Detection instrument: JASCO-1500 UV-visible absorption spectrometer.

[0066] Depend on Figure 4 It can be seen that the absorption range of compound C4TP is between 220-270nm, and the maximum absorption wavelength is 231nm. The first solution is colorless; the second solution has no obvious change after adding hydrochloric acid; the third solution has a new absorption peak at 248nm after adding nitric acid, and the solution is light yellow; and the fourth solution has a broad absorption peak at 300-700nm after adding methanesulfonic acid, and the solution is obviously green, indicating that the compound C4TP prepared by the present invention can have a specific recognition effect with methanesulfonic acid.

[0067] It can be seen from the spectrum comparison experiment that since the calixfuran macrocyclic compound prepared by the present invention has a cavity structure of a specific size, it can specifically recognize methanesulfonic acid and develop color.

Claims

1. A calixfuran macrocyclic compound having a ring structure of the general formula (I): wherein n is an integer of 3-8, preferably an integer of 4-6, more preferably 4; R1 and R2 independently represent hydrogen, halogen, cyano, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio or C6-C 12 Aryl.

2. A method for preparing the calixfuran macrocyclic compound according to claim 1, comprising the following steps: Furan is reacted with a compound of formula (a) in a solvent in the presence of an acid catalyst at a temperature of -10 to 40°C. wherein R1 and R2 are as defined in claim 1.

3. The method according to claim 2, wherein the acid catalyst is selected from hydrochloric acid, sulfuric acid and hydrobromic acid, preferably concentrated sulfuric acid.

4. The method according to claim 2 or 3, wherein the solvent is selected from the group consisting of dichloromethane, chloroform, carbon tetrachloride, tetrachloroethane, toluene, trimethylbenzene, chlorobenzene, dichlorobenzene, tetrahydrofuran, dioxane and mixtures thereof, preferably dioxane.

5. The method according to claim 2 or 3, wherein the molar ratio of furan to the compound of formula (a) is 1:(0.8-1.2), preferably 1:(0.9-1.1).

6. The method according to claim 2 or 3, wherein the molar ratio of the compound of formula (a) to the acid catalyst is 1:(2-6), preferably 1:(3-5), more preferably 1:(4-4.5).

7. The method according to claim 2 or 3, further comprising the following post-treatment step: first, pouring the reaction mixture into water, then washing the precipitated solid with a mixture of water and methanol, and finally purifying the obtained solid.

8. The single crystal of the calixfuran macrocyclic compound according to claim 1 or the calixfuran macrocyclic compound prepared by the method according to any one of claims 2 to 7, wherein n=4, R1 and R2 are both hydrogen, the single crystal is a triclinic system, the space group is P-1, and the unit cell parameters are α=117.046(2)°, β=103.519(2)°, γ=99.9910(10)°, Z=2; the crystal structure is shown in FIG3 .

9. Use of the calixfuran macrocyclic compound according to claim 1 or the calixfuran macrocyclic compound prepared by the method according to any one of claims 2 to 7 for identifying molecules, especially methanesulfonic acid.

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