Cuprofurans macrocycles, methods of making, single crystals, and recognition applications
By reacting furan with compound of formula (a) under an acid catalyst, calix furan macrocyclic compounds with specific cavity structures were prepared, solving the problems of low yield and strict reaction conditions in the prior art, and achieving specific recognition with specific acid molecules.
Patent Information
- Application Number
- CN202411668936.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2024-11-21
- Publication Date
- 2025-10-17
- Estimated Expiration
- 2044-11-21
AI Technical Summary
Existing technologies for synthesizing macrocyclic molecules generally suffer from low yields or stringent reaction conditions, making it particularly difficult to synthesize macrocyclic molecules with specific recognition functions.
Calixfuran macrocyclic compounds having the general formula (I) are prepared by reacting furan with a compound of formula (a) in the presence of an acid catalyst such as concentrated sulfuric acid at a specific temperature and solvent, and are used to identify specific acid molecules.
The preparation of calixuran macrocyclic compounds in moderate yields was achieved under mild reaction conditions, and these compounds exhibited specific recognition with certain acid molecules such as mesylate MSA.
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Abstract
Description
TECHNICAL FIELD
[0001] The present application belongs to the technical field of organic chemical synthesis, and particularly relates to a new calicifuran macrocyclic compound, a preparation method, a single crystal and application in molecular recognition. BACKGROUND
[0002] The host-guest interaction between macrocyclic molecules and small molecules or cations and anions is a common interaction in supramolecular chemistry and is ubiquitous in chemical and life systems. This interaction generally includes the recognition and combination between macrocyclic molecules (also known as hosts) and specific guest molecules or ions (such as acids or metal ions). This recognition and combination is achieved through various mechanisms, including but not limited to electrostatic interaction, hydrogen bonding, π-π stacking or hydrophobic interaction, etc.
[0003] However, the macrocyclic molecules synthesized by the prior art generally have the problems of low yield or strict reaction conditions. For this reason, 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 with acids. SUMMARY
[0004] In view of this, in a first aspect, the present application provides a calicifuran macrocyclic compound having a ring structure of general formula (I):
[0005]
[0006] wherein n is an integer of 3-8, preferably an integer of 4-6, more preferably 4;
[0007] R1and R2independently of one another represent hydrogen, halogen, cyano, C1-C6alkyl, C1-C6alkoxy, C1-C6alkylthio or C6-C10aryl. 12
[0008] In a second aspect, the present application also provides a method for preparing a calicifuran macrocyclic compound having a ring structure of general formula (I), which comprises the following steps: reacting furan with a compound of formula (a) in the presence of an acid catalyst in a solvent at a temperature of -10 to 40℃
[0009]
[0010] wherein R1and R2are as defined above,
[0011] wherein the acid catalyst is selected from hydrochloric acid, sulfuric acid and hydrobromic acid, preferably concentrated sulfuric acid.
[0012] In the present application, the solvent can be various organic solvents inert to the reaction of the present application, such as dichloromethane, trichloromethane, carbon tetrachloride, tetrachloroethane, toluene, trimethylbenzene, chlorobenzene, dichlorobenzene, tetrahydrofuran, dioxane, and mixtures thereof, preferably dioxane.
[0013] The cuprofurans macrocyclic compounds of the present application have a cavity structure of a specific size, which can be used to recognize specific acid (such as methanesulfonic acid MSA) molecules. BRIEF DESCRIPTION OF DRAWINGS
[0014] Figure 1 The hydrogen spectrum of C4TP prepared from Example 1 of the present application;
[0015] Figure 2 The mass spectrum of C4TP prepared from Example 1 of the present application;
[0016] Figure 3 The crystal structure of C4TP prepared from Example 1 of the present application;
[0017] Figure 4 The ultraviolet-visible absorption spectrum comparison of the solution of C4TP prepared from Example 1 of the present application after adding different acids. DETAILED DESCRIPTION
[0018] In the present application, all operations are carried out at room temperature (25°C) and normal pressure (101 KPa) unless otherwise stated.
[0019] The inventors found in their research that the cuprofurans macrocyclic compounds of the present application have a cavity structure of a specific size, which can be used to recognize specific acid (such as methanesulfonic acid MSA) molecules. In addition, the cuprofurans macrocyclic compounds can be prepared in moderate yield and under mild reaction conditions by the method of the present application.
[0020] Therefore, in a first aspect, the present application provides a cuprofurans macrocyclic compound having a ring structure of general formula (I):
[0021]
[0022] wherein n is an integer from 3 to 8, preferably an integer from 4 to 6, more preferably 4 and 6;
[0023] R1and R2, independently of each other, represent hydrogen, halogen, cyano, C1-C6alkyl, C1-C6alkoxy, C1-C6alkylthio or C6-C 12 aryl;
[0024] Preferably, halogen is selected from fluorine, chlorine, bromine and iodine.
[0025] In a preferred embodiment of the present application, n is 4 or 6, more preferably 4.
[0026] In a preferred embodiment of the present application, R1and R2independently of one another represent hydrogen, halogen, C1-C6alkyl or C6-C 12 aryl.
[0027] In a preferred embodiment of the present application, R1and R2independently of one another represent hydrogen.
[0028] In a preferred embodiment of the present application, the calicifungin macrocyclic compound of the present application has the following structure (i.e., n = 4 in general formula (I) and R1and R2independently of one another represent hydrogen, also referred to herein as "C4TP"):
[0029]
[0030] In a second aspect, the present application also provides a process for the preparation of a calicifungin macrocyclic compound having a ring structure of general formula (I) comprising the step of reacting furan with a compound of formula (a) in the presence of an acid catalyst in a solvent at a temperature ranging from -10 to 40 °C
[0031]
[0032] wherein R1and R2are as defined above,
[0033] wherein the acid catalyst is selected from the group consisting of hydrochloric acid, sulfuric acid and hydrobromic acid, preferably concentrated sulfuric acid.
[0034] In the present application, the term "concentrated sulfuric acid" means a mixture of sulfuric acid (H2SO4) with water having a volume percentage of sulfuric acid greater than 60%, preferably greater than 80%, more preferably greater than 90%, in particular from 90% to 91%.
[0035] In the present application, the solvent is selected from various organic solvents which are inert to the reaction of the present application, such as dichloromethane, trichloromethane, carbon tetrachloride, tetrachloroethane, toluene, trimethylbenzene, chlorobenzene, dichlorobenzene, tetrahydrofuran, dioxane and mixtures thereof, preferably dioxane.
[0036] In a preferred embodiment of the present application, the molar ratio of the furan to the compound of formula (a) can be 1 : (0.8-1.2), preferably 1 : (0.9 -1.1), more preferably 1 : 1.
[0037] In a preferred embodiment of the present application, the concentration of the compound of formula (a) in the solvent can be (0.1-1.0) mmol / mL, preferably (0.2-0.8) mmol / mL, more preferably (0.25-0.4) mmol / mL.
[0038] In a preferred embodiment of the present application, the molar ratio of the compound of formula (a) to the acid catalyst can be 1 : (2-6), preferably 1 : (3-5), more preferably 1 : (4-4.5).
[0039] In a preferred embodiment of the present application, the reaction time can be 4 to 24 hours, preferably 5 to 15 hours, more preferably 8 to 13 hours.
[0040] In a preferred embodiment of the present application, when concentrated sulfuric acid (e.g. having a concentration of 70-95% by volume) is used as the acid catalyst, 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) for the reaction.
[0041] In a preferred embodiment of the present application, the reaction temperature can be -5 to 35°C, preferably 15 to 30°C.
[0042] In a preferred embodiment of the present application, after the reaction is completed, the post-treatment can be performed by first pouring the reaction mixture into water, and then washing the precipitated solid with a mixture of water and / or methanol (preferably a mixture of water and methanol at a volume ratio of 1 : (0.5-2)). Finally, the obtained solid is further purified using a purification method known in the art, for example, purified by silica gel column chromatography (gradient elution, e.g. dichloromethane to ethyl acetate).
[0043] The various embodiments described herein can be combined with each other. Combinations that do not violate the laws of nature and are thus excluded by those skilled in the art from his / her professional knowledge are not included.
[0044] Hereinafter, the present application will be described in more detail with reference to the following examples. The examples disclosed below are for illustrative purposes only and are not intended to limit the present application. Those skilled in the art can make various modifications, additions and substitutions to the examples of the present application without departing from the scope and spirit of the present application.
[0045] I. Preparation Examples
[0046] Example 1
[0047] In a 100 mL round bottom flask, furan (0.68 g, 10 mmol) and tetrahydropyranone (1 g, 10 mmol) in 1,4-dioxane (30 mL) were added and cooled to 0 °C, 90.5% sulfuric acid (2.5 mL, 41.8 mmol) was added dropwise, and stirred at room temperature for 12 h, the solution appeared 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 resulting solid was further purified by silica gel column chromatography (dichloromethane to ethyl acetate) to obtain white solid product C4TP with a yield of 20%.
[0048]
[0049] C4TP 1 H NMR (400 MHz, CDC13, 298 K): δ = 5.93 (s, 8H), 3.66 (t, J = 28.5 Hz, 16H), 2.15 (t, J = 28.5 Hz, 16H). HRMS (MALDI): calcd (%) for C
[0050] = 28.5 Hz, 16H), 2.15 (t, J = 28.5 Hz, 16H). HRMS (MALDI): calcd (%) for C 36 H 40 O8Na + : 623.2616, found [M+Na] + : 623.3363.
[0051] II. Crystal testing
[0052] 1. Preparation of crystals
[0053] The solid C4TP (5 mg) prepared from Example 1 was dissolved in a mixture of dichloromethane and methanol (3 mL and 2 mL), and light yellow block crystals were precipitated at room temperature as the solvent slowly evaporated.
[0054] 2. Crystal testing
[0055] Detection instrument: Bruker APEX-II CCD single crystal diffractometer
[0056] 2.1 Single crystal analysis was performed on the crystal of C4TP prepared by the above method, and the tested single crystallographic data is shown in Table 1.
[0057] Table 1
[0058]
[0059]
[0060] Therefore, the calicifurans macrocycle with the ring structure of general formula (I) (wherein n=4, R1 and R2 are both hydrogen) of the present application belongs to triclinic crystal type-P-1, C2 axis symmetry, wherein three furans are upward, one furan is downward, tetrahydropyran is in chair conformation, and the cavity size is about
[0061] III. Ultraviolet-visible absorption spectrum test
[0062] 1. Preparation of sample
[0063] The compound C4TP (6 mg) prepared in Example 1 was dissolved in dichloromethane (100 mL), and four portions, each of 5 mL, were taken, the first portion was the reference group, and 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, and the ultraviolet-visible absorption spectrum was tested at room temperature, as shown in Figure 4 .
[0064] 2. Sample test
[0065] Detection instrument: JASCO-1500 ultraviolet-visible absorption spectrometer.
[0066] As can be seen from Figure 4 , the absorption range of the compound C4TP is between 220-270 nm, and the maximum absorption wavelength is 231 nm. The first portion of the solution is colorless; the second portion has no obvious change after adding hydrochloric acid; the third portion has a new absorption peak at 248 nm after adding nitric acid, and the solution is light yellow; and the fourth portion has a wide absorption peak at 300-700 nm after adding methanesulfonic acid, and the solution is obviously green, indicating that the compound C4TP prepared in the present application can have specific recognition with methanesulfonic acid.
[0067] As can be seen from the spectrum comparison experiment, since the calicifurans macrocycle prepared in the present application has a specific size of cavity structure, it can have specific recognition with methanesulfonic acid and show color.
Claims
1. Calixfuran macrocyclic compounds, whose structure is:
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 H.
3. The method according to claim 2, wherein the acid catalyst is 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. The method according to claim 4 , wherein the solvent is selected from dioxane.
6. 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).
7. The method according to claim 6, wherein the molar ratio of furan to the compound of formula (a) is 1:(0.9-1.1).
8. 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).
9. The method according to claim 8, wherein the molar ratio of the compound of formula (a) to the acid catalyst is 1:(3-5).
10. The method according to claim 9, wherein the molar ratio of the compound of formula (a) to the acid catalyst is 1:(4-4.5).
11. The method according to claim 2 or 3, further comprising the following post-treatment steps: 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.
12. The single crystal of the calixfuran macrocyclic compound according to claim 1, wherein the single crystal is a triclinic crystal 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 .
13. Use of the calixfuran macrocyclic compound according to claim 1 for identifying methanesulfonic acid.