Oxazole compound as well as preparation method and application thereof
By using ferric chloride, iodine element and oxygen as oxidants in organic solvents, the reaction conditions are controlled to generate oxazole compounds, which solves the problem of excessive use of reagents and product separation in the prior art, and achieves efficient and low-cost oxazole compounds preparation and wide application.
Patent Information
- Application Number
- CN202510683214.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-05-26
- Publication Date
- 2025-08-08
AI Technical Summary
The existing oxazole compound synthesis methods have excessive use of reagents, difficulty in removing oxidant reduction products, complex product separation and purification, high catalyst cost and difficulty in removing organic impurities, and the application scope is limited.
Iron chloride, iodine element and oxygen are used as oxidative agents to oxidize and cyclize α-aminoketone hydrochloride compounds and aldehyde compounds in an organic solvent to control the reaction conditions to form oxidazole compounds. The post-treatment is separated by silica gel column chromatography.
It has achieved high yield, simple, environmentally friendly and low-cost preparation of oxazole compounds, and is suitable for fluorescent dyes, OLED materials, drugs, catalysts and chemical probes, and has expanded its application scope.
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Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of oxazole compounds, and in particular to an oxazole compound and a preparation method and application thereof. Background Art
[0002] Oxazole compounds are widely found in numerous natural products and form the core backbone of many pharmaceutical and bioactive molecules. Due to their unique chemical structure, oxazoles have broad applications in a variety of fields, including fluorescent dyes, OLED materials, pharmaceuticals, catalysts, functional polymers, and chemical probes. Consequently, the synthesis of oxazoles has attracted considerable attention. Numerous methods exist for the preparation of oxazoles, including the classic Robinson-Gabriel synthesis, which involves the dehydration of 2-acylaminoketones; the Fischer synthesis, which involves the reaction of cyanohydrins with aldehydes; and the Bredereck and Van Leusen reactions.
[0003] The oxidative cyclization of α-aminoketone hydrochlorides with aldehydes to form oxazoles is a popular and practically applicable method. This not only constitutes an important route for the synthesis of oxazoles but also offers significant synthetic advantages. However, currently reported methods for the oxidation of α-aminoketone hydrochlorides with aldehydes to oxazoles typically require the use of expensive oxidants, often using a significant excess of the α-aminoketone hydrochloride, and requiring large amounts of iodine as the oxidant (C.-F. Wan, L.-F. Gao, Q. Wang, J.-T. Zhang, Z.-Y. Wang, Org. Lett. 12 (2010) 3902−3905). Existing synthetic methods often suffer from issues such as excessive reagent use, removal of oxidant reduction products, product separation and purification, catalyst cost control and recovery, and removal of organic impurities. Summary of the Invention
[0004] In view of the shortcomings of the existing technology, the first purpose of the present invention is to provide a method for preparing oxazole compounds, which has the advantages of high reaction yield and convenient separation, and demonstrates the excellent environmental protection, simplicity, high efficiency, mildness and low cost economy of the new process technology.
[0005] The second object of the present invention is to provide an oxazole compound, which has the advantages of being widely used in the fields of fluorescent dyes, OLED materials, ligands, catalysts, functional polymers and chemical probes.
[0006] The third object of the present invention is to provide an application of an oxazole compound, which has the advantage of a wide range of applications.
[0007] To achieve the above first object, the present invention provides the following technical solutions:
[0008] A method for preparing an oxazole compound, the route of the preparation method is as follows:
[0009] ;
[0010] The preparation method comprises the following steps: in an organic solvent, under the action of ferric chloride, elemental iodine and oxygen, the compound of the above formula (A) and the compound of the above formula (B) undergo an oxidative cyclization reaction, and after completion of the reaction, the compound of the above formula (C) is obtained by post-treatment;
[0011] wherein R1 is selected from C1~C6 alkyl, or substituted or unsubstituted phenyl, the substituent of phenyl is selected from halogen, or C3~C6 alkoxy; and R2 is selected from H, or C1~C6 alkyl;
[0012] Alternatively, the R1 and R2 are connected to form a ring;
[0013] And / or, R3 is selected from substituted or unsubstituted phenyl, cycloalkyl, or furyl, and the substituent of phenyl is selected from halogen, C1~C6 haloalkyl, C2~C6 ester, or C1~C6 alkoxy.
[0014] Specifically, in the above-mentioned compound of the present invention,
[0015] The specific meaning of the "alkyl" refers to a straight-chain or branched alkyl group, and non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, tert-pentyl or n-hexyl;
[0016] The specific meaning of the "phenyl" is a group formed by removing one H atom from a benzene ring;
[0017] The specific meaning of the "halogen" is a halogen element, which can be, for example, F, Cl, Br or I;
[0018] The specific meaning of the "haloalkyl" is a group formed by connecting several "halogen" and "alkyl" as defined above;
[0019] The specific meaning of the "alkoxy" is the group formed by connecting the "alkyl" defined above and an O atom, and can be, for example, methoxy, ethoxy, propoxy, butoxy or pentoxy, etc.
[0020] The specific meaning of the "cycloalkyl" is a group formed by removing one H atom from a cycloalkane, and can be, for example, cyclopropane, cyclobutane, cyclopentane or cyclohexane, etc.
[0021] The specific meaning of the "furyl" is a group formed by removing one H atom from a five-membered heterocyclic ring containing an O atom, and can be, for example, a group formed by removing one H atom from furan or tetrahydrofuran;
[0022] The “ester group” refers to the ester functional group in a carboxylic acid derivative, and its simplified structural formula is -COOR (R is generally an alkyl group or other non-H group).
[0023] Further, the R1 is selected from methyl, phenyl, p-chlorophenyl, or o-methoxyphenyl;
[0024] And / or, said R2 is selected from H, or methyl;
[0025] And / or, R3 is selected from phenyl, p-bromophenyl, p-trifluoromethylphenyl, p-methylformatephenyl, o-methoxyphenyl, m-methoxyphenyl, p-methoxyphenyl, cyclopropane, or furyl.
[0026] Furthermore, the organic solvent is anisole.
[0027] Furthermore, during the oxidative cyclization reaction, the molar ratio of the compound of formula (A) to the compound of formula (B) is controlled to be 1.0-2.0:1.0.
[0028] Furthermore, during the oxidative cyclization reaction, the molar ratio of the compound of formula (B), ferric chloride and elemental iodine is controlled to be 1.0:0.1-0.2:0.1-0.2.
[0029] Furthermore, during the oxidative cyclization reaction, ferric chloride, elemental iodine, the compound of formula (A) and the compound of formula (B) are stirred in an organic solvent in advance, and then the air in the reaction environment is replaced with 0.8-1.2 atm of oxygen.
[0030] Furthermore, during the oxidative cyclization reaction, the reaction temperature is controlled to be 80-100° C., and the reaction time is 3.5-4.5 h.
[0031] Furthermore, after the reaction is completed, the reactant is dried under reduced pressure, and the crude reactant is eluted on a silica gel column chromatography using hexane-ethyl acetate as an eluent to obtain the compound of the above formula (C).
[0032] To achieve the above second purpose, the present invention provides the following technical solutions:
[0033] An oxazole compound selected from the compound of formula (C) prepared by the above method, or selected from the stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, pharmaceutically acceptable esters or pharmaceutically acceptable solvates of the compound.
[0034] To achieve the third objective, the present invention provides the following technical solutions:
[0035] An application of an oxazole compound, wherein the oxazole compound is used in the preparation of fluorescent dyes, OLED materials, drugs, catalysts, functional polymers, and chemical probes. The oxazole compound is selected from the compound of formula (C) prepared by the above method, or is selected from the stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, pharmaceutically acceptable esters, or pharmaceutically acceptable solvates of the compound.
[0036] In summary, the beneficial technical effects of the present invention are as follows: the preparation method of the present invention uses α-aminoketone hydrochlorides represented by formula (A) and aldehyde compounds represented by formula (B) to undergo an oxidative cyclization reaction under appropriate reaction conditions to directly generate oxazole compounds represented by formula (C). The method uses inexpensive ferric chloride, elemental iodine and green and environmentally friendly oxygen as oxidants, avoiding the problem of increased material costs caused by the use of excessive catalysts and the problems of separation and purification caused by the use of organic oxidants. Oxygen is converted into water after participating in the reaction. The reaction system is free of other impurities and the introduction of organic or inorganic salts, and the reaction yield is high and separation is convenient, demonstrating the excellent environmental protection, simplicity, high efficiency, mildness and low-cost economy of the new process technology. DETAILED DESCRIPTION
[0037] In order to make the technical means, creative features, objectives and functions achieved by the present invention clearer and easier to understand, the present invention is further elaborated below in conjunction with specific implementation methods.
[0038] Example 1: A method for preparing an oxazole compound disclosed in the present invention. The preparation method is as follows:
[0039] ;
[0040] The preparation method comprises the following steps: at room temperature and pressure, 25.6 g of α-aminoacetophenone hydrochloride (0.15 mol), 10.1 g of benzaldehyde, 300 mL of anisole (0.10 mol), 1.62 g of ferric chloride (0.01 mol), and 2.54 g of elemental iodine (0.01 mol) are sequentially added to a 500 mL three-necked flask. The air in the reaction environment is then replaced with 1.0 atm of oxygen under vigorous stirring. The mixture is stirred at 90°C for 4 hours. After the reaction is complete, the reactants are evaporated under reduced pressure and the crude product is eluted on a silica gel column with hexane-ethyl acetate as the eluent to obtain 18.3 g of the target product, 2,5-diphenyloxazole, in an 83% yield. 1 H NMR (400 MHz, CDCl3) δ 8.12 (dd, J = 7.7, 2.1 Hz, 2H), 7.73 (dd, J = 8.5, 1.4 Hz, 2H), 7.53–7.42 (m, 6H), 7.35 (t, J = 7.4 Hz, 1 H). 13 C NMR (100 MHz, CDCl3) δ 161.3,151.4, 130.5, 129.1, 129.0, 128.6, 128.1, 127.4, 126.4, 124.3, 123.4.
[0041] Example 2: A method for preparing an oxazole compound disclosed in the present invention. The preparation method is as follows:
[0042] ;
[0043] The preparation method comprises the following steps: 25.6 g of α-aminoacetophenone hydrochloride, 12.4 g of p-fluorobenzaldehyde, 300 mL of anisole, 1.62 g of ferric chloride, and 2.54 g of iodine are sequentially added to a 500 mL three-necked flask at room temperature and pressure. Subsequently, under sufficient stirring, the air in the replacement reaction environment is replaced with 1.0 atm of oxygen, and the mixture is stirred at 90°C for 4 hours. After completion of the reaction, the reactants are dried under reduced pressure and the crude product is eluted on a silica gel column chromatography using hexane-ethyl acetate as an eluent to obtain 21.0 g of the target product, 2-p-fluorophenyl-5-phenyloxazole, in a yield of 88%. 1 H NMR (400 MHz, CDCl3) δ 8.15–8.04 (m, 2H),7.77–7.65 (m, 2H), 7.50–7.40 (m, 3H), 7.39–7.32 (m, 1 H), 7.18 (t, J = 8.7 Hz,2H). 13C NMR (100 MHz, CDCl3) δ 164.2 (d, J = 250.0 Hz), 160.5, 151.5, 129.1,128.6 (d, J = 9.0 Hz), 128.5, 128.0, 124.3, 123.9 (d, J = 2.0 Hz), 123.5,116.2 (d, J = 22.0 Hz).
[0044] Example 3: A method for preparing an oxazole compound disclosed in the present invention. The preparation method is as follows:
[0045] ;
[0046] The preparation method comprises the following steps: 25.6 g of α-aminoacetophenone hydrochloride, 18.4 g of p-bromobenzaldehyde, 500 mL of anisole, 1.62 g of ferric chloride, and 2.54 g of iodine are sequentially added to a 500 mL three-necked flask at room temperature and pressure. Subsequently, under sufficient stirring, the air in the replacement reaction environment is replaced with 1.0 atm of oxygen, and the mixture is stirred at 90°C for 4 hours. After completion of the reaction, the reactants are dried under reduced pressure and the crude product is eluted on a silica gel column chromatography using hexane-ethyl acetate as an eluent to obtain 22.4 g of the target product, 2-p-bromophenyl-5-phenyloxazole, with a yield of 75%. 1 H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 8.5 Hz, 2H), 7.65 (d, J = 7.6 Hz, 2H), 7.56 (d, J = 8.5 Hz, 2H), 7.48–7.35 (m, 3H), 7.32 (t, J = 7.4 Hz, 1 H). 13 C NMR (100 MHz, CDCl3) δ 160.2, 151.5, 132.0,128.9, 128.6, 127.7, 127.6, 126.3, 124.7, 124.2, 123.5.
[0047] Example 4: A method for preparing an oxazole compound disclosed in the present invention. The preparation method is as follows:
[0048] ;
[0049] The preparation method comprises the following steps: 25.6 g of α-aminoacetophenone hydrochloride, 13.6 g of p-anisaldehyde, 500 mL of anisole, 1.62 g of ferric chloride, and 2.54 g of iodine are sequentially added to a 500 mL three-necked flask at room temperature and pressure. Subsequently, under sufficient stirring, the air in the replacement reaction environment is replaced with 1.0 atm of oxygen, and the mixture is stirred at 90°C for 4 hours. After completion of the reaction, the reactants are dried under reduced pressure and the crude reactant is eluted on a silica gel column chromatography using hexane-ethyl acetate as an eluent to obtain 23.1 g of the target product, 2-p-methoxyphenyl-5-phenyloxazole, with a yield of 92%. 1 H NMR (400 MHz, CDCl3) δ 8.08–8.02 (m,2H), 7.75–7.66 (m, 2H), 7.47–7.42 (m, 2H), 7.41 (s, 1 H), 7.36–7.30 (m, 1 H),7.00 (d, J = 8.9 Hz, 2H), 3.88 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 161.5,161.4, 150.9, 129.0, 128.4, 128.3, 128.1, 124.2, 123.3, 120.3, 114.4, 55.5.
[0050] Example 5: A method for preparing an oxazole compound disclosed in the present invention. The preparation method is as follows:
[0051] ;
[0052] The preparation method comprises the following steps: 25.6 g of α-aminoacetophenone hydrochloride, 16.4 g of methyl paraformylbenzoate, 500 mL of anisole, 1.62 g of ferric chloride, and 2.54 g of elemental iodine are sequentially added to a 500 mL three-necked flask at room temperature and pressure. Subsequently, under sufficient stirring, the air in the replacement reaction environment is replaced with 1.0 atm of oxygen, and the mixture is stirred at 90° C. for 4 hours. After completion of the reaction, the reactants are dried under reduced pressure and the crude reactant is eluted on a silica gel column chromatography using hexane-ethyl acetate as an eluent to obtain 23.7 g of the target product, 4-(5-phenyloxazol-2-yl)-methyl benzoate, with a yield of 85%. 1 H NMR (400 MHz, CDCl3) δ 8.25–8.07 (m, 4H), 7.80–7.65 (m, 2H), 7.53–7.42 (m, 3H), 7.41–7.32 (m, 1 H), 3.95(s, 3H). 13C NMR (100 MHz, CDCl3) δ 166.6, 160.2, 152.2, 131.5, 131.3, 130.2,129.1, 128.9, 127.8, 126.2, 124.5, 124.0, 52.4.
[0053] Example 6: A method for preparing an oxazole compound disclosed in the present invention. The route of the preparation method is as follows:
[0054] ;
[0055] The preparation method comprises the following steps: 25.6 g of α-aminoacetophenone hydrochloride, 13.6 g of m-methoxybenzaldehyde, 500 mL of anisole, 1.62 g of ferric chloride, and 2.54 g of elemental iodine are sequentially added to a 500 mL three-necked flask at room temperature and pressure. Subsequently, under sufficient stirring, the air in the replacement reaction environment is replaced with 1.0 atm of oxygen, and the mixture is stirred at 90°C for 4 hours. After completion of the reaction, the reactants are dried under reduced pressure and the crude reactant is eluted on a silica gel column chromatography using hexane-ethyl acetate as an eluent to obtain 21.1 g of the target product, 2-m-methoxyphenyl-5-phenyloxazole, with a yield of 90%. 1 H NMR (400 MHz, CDCl3) δ 7.96–7.86 (m,2H), 7.75–7.66 (m, 2H), 7.47–7.39 (m, 3H), 7.33 (p, J = 7.5 Hz, 2H), 7.25 (d,J = 7.5 Hz, 1 H), 2.42 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 161.5, 151.3, 138.7,131.4, 129.1, 128.9, 128.6, 128.1, 127.4, 127.0, 124.3, 123.6, 123.4, 21.5.
[0056] Example 7: A method for preparing an oxazole compound disclosed in the present invention. The preparation method is as follows:
[0057] ;
[0058] The preparation method comprises the following steps: 25.6 g of α-aminoacetophenone hydrochloride, 13.6 g of o-anisaldehyde, 500 mL of anisole, 1.62 g of ferric chloride, and 2.54 g of iodine are sequentially added to a 500 mL three-necked flask at room temperature and pressure. Subsequently, under sufficient stirring, the air in the replacement reaction environment is replaced with 1.0 atm of oxygen, and the mixture is stirred at 90°C for 4 hours. After completion of the reaction, the reactants are dried under reduced pressure and the crude product is eluted on a silica gel column chromatography using hexane-ethyl acetate as an eluent to obtain 19.7 g of the target product, 2-o-methoxyphenyl-5-phenyloxazole, with a yield of 84%. 1 H NMR (400 MHz, CDCl3) δ 8.10 (dd, J =7.8, 1.9 Hz, 1 H), 7.73 (dd, J = 8.4, 1.3 Hz, 2H), 7.49 (s, 1 H), 7.48–7.43 (m,2H), 7.39–7.30 (m, 4H), 2.77 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 161.7, 151.0,137.4, 131.8, 130.1, 129.1, 128.9, 128.5, 128.2, 126.5, 126.2, 124.3, 123.2,22.3.
[0059] Example 8: A method for preparing an oxazole compound disclosed in the present invention. The route of the preparation method is as follows:
[0060] ;
[0061] The preparation method comprises the following steps: 25.6 g of α-aminoacetophenone hydrochloride, 9.6 g of furfural, 500 mL of anisole, 1.62 g of ferric chloride, and 2.54 g of iodine are sequentially added to a 500 mL three-necked flask at room temperature and pressure. Subsequently, the air in the replacement reaction environment is replaced with 1.0 atm of oxygen under sufficient stirring, and the mixture is stirred at 90° C. for 4 hours. After completion of the reaction, the reactants are dried under reduced pressure and the crude product is eluted on a silica gel column chromatography using hexane-ethyl acetate as an eluent to obtain 15.8 g of the target product, 2-(furan-2-yl)-5-phenyloxazole, in a yield of 75%. 1 H NMR (400 MHz, CDCl3) δ 7.69 (dd, J = 7.2,1.7 Hz, 2H), 7.58 (d, J = 2.1 Hz, 1 H), 7.47–7.39 (m, 3H), 7.33 (t, J = 7.5Hz,1 H), 7.08 (d, J = 3.4 Hz, 1 H), 6.56 (dd, J = 3.5, 1.8 Hz, 1 H). 13 C NMR (100MHz, CDCl3) δ 154.0, 150.9, 144.6, 143.0, 129.0, 128.7, 127.7, 124.3, 123.3,112.0, 111.6.
[0062] Example 9: A method for preparing an oxazole compound disclosed in the present invention. The preparation method is as follows:
[0063] ;
[0064] The preparation method comprises the following steps: 25.6 g of α-aminoacetophenone hydrochloride, 7.0 g of cyclopropylcarboxaldehyde, 500 mL of anisole, 1.62 g of ferric chloride, and 2.54 g of iodine are sequentially added to a 500 mL three-necked flask at room temperature and pressure. Subsequently, under sufficient stirring, the air in the replacement reaction environment is replaced with 1.0 atm of oxygen, and the mixture is stirred at 90°C for 4 hours. After completion of the reaction, the reactants are dried under reduced pressure and the crude reactant is eluted on a silica gel column chromatography using hexane-ethyl acetate as an eluent to obtain 17.3 g of the target product, 2-cyclopropyl-5-phenyloxazole, with a yield of 76%. 1 H NMR (400 MHz, CDCl3) δ 7.65–7.57 (m, 2H), 7.40 (td, J = 6.9, 6.4, 1.8 Hz, 2H), 7.33–7.27 (m, 1 H), 7.22 (s, 1 H), 2.87 (tt, J =11.4, 3.8 Hz, 1 H), 2.17–2.09 (m, 2H), 1.89–1.81 (m, 2H), 1.76–1.59 (m, 3H), 1.46–1.27 (m, 3H). 13 C NMR (100 MHz, CDCl3) δ 168.0, 150.7, 129.0, 128.4,128.2, 124.1, 121.4, 37.7, 30.7, 25.9, 25.7.
[0065] Example 10: A method for preparing an oxazole compound disclosed in the present invention. The route of the preparation method is as follows:
[0066] ;
[0067] The preparation method comprises the following steps: 30.7 g of α-amino-p-chloroacetophenone hydrochloride, 10.1 g of benzaldehyde, 500 mL of anisole, 1.62 g of ferric chloride, and 2.54 g of iodine are sequentially added to a 500 mL three-necked flask at room temperature and pressure. Subsequently, under sufficient stirring, the air in the replacement reaction environment is replaced with 1.0 atm of oxygen, and the mixture is stirred at 90 ° C for 4 hours. After completion of the reaction, the reactants are dried under reduced pressure, and the crude reactant is eluted on a silica gel column chromatography using hexane-ethyl acetate as an eluent to obtain 19.6 g of the target product 2-phenyl-5-p-chlorophenyloxazole in a yield of 77%. 1 H NMR (400 MHz, CDCl3) δ 8.13–8.05 (m, 2H), 7.66–7.61 (m, 2H), 7.48 (dd, J = 5.1, 2.3 Hz, 3H), 7.44–7.39 (m, 3H). 13 C NMR (100 MHz, CDCl3) δ 161.5, 150.4, 134.3, 130.6, 129.3, 129.0, 127.3, 126.6,126.4, 125.5, 123.9.
[0068] Example 11: A method for preparing an oxazole compound disclosed in the present invention. The preparation method is as follows:
[0069] ;
[0070] The preparation method comprises the following steps: 30.1 g of α-amino-o-methoxyacetophenone hydrochloride, 10.1 g of benzaldehyde, 500 mL of anisole, 1.62 g of ferric chloride, and 2.54 g of iodine are sequentially added to a 500 mL three-necked flask at room temperature and pressure. Subsequently, under sufficient stirring, the air in the replacement reaction environment is replaced with 1.0 atm of oxygen, and the mixture is stirred at 90°C for 4 hours. After completion of the reaction, the reactants are dried under reduced pressure and the crude reactant is eluted on a silica gel column chromatography using hexane-ethyl acetate as an eluent to obtain 20.0 g of the target product, 2-phenyl-5-o-methoxyphenyloxazole, with a yield of 80%. 1 H NMR (400 MHz, CDCl3) δ 8.16–8.07 (m,2H), 7.54–7.46 (m, 3H), 7.45 (s, 1 H), 7.36 (t, J = 7.8 Hz, 1 H), 7.32 (dt, J =7.7, 1.4 Hz, 1 H), 7.26–7.24 (m,1 H), 6.90 (ddd, J = 7.9, 2.6, 1.3 Hz, 1 H), 3.89 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 161.3, 160.2, 151.3, 130.6, 130.2,129.3, 129.0, 127.5, 126.5, 123.8, 116.9, 114.2, 109.9, 55.5.
[0071] Example 12: A method for preparing an oxazole compound disclosed in the present invention. The preparation method is as follows:
[0072] ;
[0073] The preparation method comprises the following steps: 18.4 g of α-aminobutanone hydrochloride, 10.1 g of benzaldehyde, 500 mL of anisole, 1.62 g of ferric chloride, and 2.54 g of elemental iodine are sequentially added to a 500 mL three-necked flask at room temperature and pressure. Subsequently, under sufficient stirring, the air in the reaction environment is replaced with 1.0 atm of oxygen, and the mixture is stirred at 90°C for 4 hours. After completion of the reaction, the reactants are dried under reduced pressure and the crude product is eluted on a silica gel column chromatography using hexane-ethyl acetate as the eluent to obtain 13.3 g of the target product, 2-phenyl-4,5-dimethyloxazole, with a yield of 77%. 1 H NMR (400 MHz, CDCl3) δ 8.13–7.87 (m, 2H), 7.56–7.32 (m, 3H), 2.31 (s, 3H), 2.16 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 159.26,143.55, 131.96, 129.8, 128.8, 127.9, 126.0, 11.4, 10.2.
[0074] Example 13: An oxazole compound disclosed in the present invention, selected from the oxazole compound prepared by any one of the methods of Examples 1 to 12, or selected from the stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, pharmaceutically acceptable esters or pharmaceutically acceptable solvates of the above-mentioned oxazole compounds.
[0075] Example 14: An application of an oxazole compound disclosed in the present invention, the application of the oxazole compound in the preparation of fluorescent dyes, OLED materials, drugs, catalysts, functional polymers and chemical probes, the oxazole compound is selected from the oxazole compound prepared by any method of Examples 1 to 12, or selected from the stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, pharmaceutically acceptable esters or pharmaceutically acceptable solvates of the above-mentioned oxazole compounds.
[0076] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not limiting. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the purpose and scope of the technical solutions of the present invention, which should all be included in the scope of the claims of the present invention.
Claims
1. A method for preparing an oxazole compound, characterized in that: The route of the preparation method is as follows, ； The preparation method comprises the following steps: in an organic solvent, under the action of ferric chloride, elemental iodine and oxygen, the compound of the above formula (A) and the compound of the above formula (B) undergo an oxidative cyclization reaction, and after completion of the reaction, the compound of the above formula (C) is obtained by post-treatment; wherein R1 is selected from C1~C6 alkyl, or substituted or unsubstituted phenyl, the substituent of phenyl is selected from halogen, or C3~C6 alkoxy; and R2 is selected from H, or C1~C6 alkyl; Alternatively, the R1 and R2 are connected to form a ring; And / or, R3 is selected from substituted or unsubstituted phenyl, cycloalkyl, or furyl, and the substituent of phenyl is selected from halogen, C1~C6 haloalkyl, C2~C6 ester, or C1~C6 alkoxy.
2. The method for preparing an oxazole compound according to claim 1, wherein: Said R1 is selected from methyl, phenyl, p-chlorophenyl, or o-methoxyphenyl; And / or, said R2 is selected from H, or methyl; And / or, R3 is selected from phenyl, p-bromophenyl, p-trifluoromethylphenyl, p-methylformatephenyl, o-methoxyphenyl, m-methoxyphenyl, p-methoxyphenyl, cyclopropane, or furyl.
3. The method for preparing an oxazole compound according to claim 1, wherein: The organic solvent is anisole.
4. The method for preparing an oxazole compound according to claim 1, wherein: During the oxidative cyclization reaction, the molar ratio of the compound of formula (A) to the compound of formula (B) is controlled to be 1.0-2.0:1.
0.
5. The method for preparing an oxazole compound according to claim 1, wherein: During the oxidative cyclization reaction, the molar ratio of the compound of formula (B), ferric chloride and elemental iodine is controlled to be 1.0:0.1-0.2:0.1-0.
2.
6. The method for preparing an oxazole compound according to claim 1, wherein: During the oxidative cyclization reaction, ferric chloride, elemental iodine, the compound of formula (A) and the compound of formula (B) are stirred in an organic solvent beforehand, and then the air in the reaction environment is replaced with 0.8-1.2 atm of oxygen.
7. The method for preparing an oxazole compound according to claim 1, wherein: During the oxidative cyclization reaction, the reaction temperature is controlled to be 80-100° C., and the reaction time is 3.5-4.5 h.
8. The method for preparing an oxazole compound according to claim 1, wherein: After the reaction is completed, the reactant is dried under reduced pressure and the crude reactant is eluted on a silica gel column chromatography using hexane-ethyl acetate as an eluent to obtain the compound of the above formula (C).
9. An oxazole compound, characterized in that: The compound of formula (C) prepared by the method according to any one of claims 1 to 8, or a stereoisomer, prodrug, crystal form, pharmaceutically acceptable salt, pharmaceutically acceptable ester or pharmaceutically acceptable solvate of the compound.
10. An application of an oxazole compound, characterized in that: The use of the oxazole compound in the preparation of fluorescent dyes, OLED materials, drugs, catalysts, functional polymers and chemical probes, wherein the oxazole compound is selected from the compound of formula (C) prepared by the method according to any one of claims 1 to 8, or is selected from the stereoisomers, prodrugs, crystal forms, pharmaceutically acceptable salts, pharmaceutically acceptable esters or pharmaceutically acceptable solvates of the compound.