A method for synthesizing 2,3-diacyl tetrasubstituted furan
By using the addition cyclization isomerization reaction of terminal aromatic alkynes and 1,2-diones, the problems of complex synthesis methods and substrate limitations of tetrasubstituted furans were solved, and efficient and extensive diacyl tetrasubstituted furans were achieved with a yield of 75%.
Patent Information
- Application Number
- CN202411473476.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2024-10-22
- Publication Date
- 2026-02-27
- Estimated Expiration
- 2044-10-22
AI Technical Summary
Existing methods for synthesizing tetrasubstituted furans are complex to operate and have substrate limitations, making it difficult to achieve efficient and widespread synthesis.
2,3-diacyltetrasubstituted furan was synthesized from terminal aromatic alkynes and 1,2-dione via an addition cyclization isomerization reaction. Cu(OAc)2·H2O and DMAP were used as catalysts, dimethyl sulfoxide was used as solvent, the reaction temperature was 100℃, and the reaction time was 72 hours.
This provides a synthetic method with inexpensive and readily available raw materials, simple operation, mild conditions, a wide substrate range, and a yield of up to 75%.
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Figure CN119350274B_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The application belongs to the technical field of organic compound synthesis, and particularly relates to a synthesis method of 2,3-diacyl tetrasubstituted furan. BACKGROUND
[0002] Polysubstituted furan is an important component of many natural products, drugs and functional materials with biological activity, and furan compounds can also be used as an important component of organic synthesis. In the past few decades, chemists have paid extensive attention to and made efforts on the synthesis of polysubstituted furan, and various excellent synthesis strategies have been designed for the construction of tetrasubstituted furan.
[0003]
[0004] At present, there are mainly the following four strategies for the synthesis of tetrasubstituted furan: 1) cyclization isomerization of allene and enynol, ketone and its derivatives; 2) tandem cyclization of functionalized alkenes, alkynes, allenes and carbonyl compounds; 3) three-component tandem reaction of terminal alkyne and aldehyde, nitrile or acyl compound; 4) transition metal-catalyzed cyclization of activated alkenes and allene esters. These methods have made great progress in the construction of tetrasubstituted furan skeleton, but there are still complex operations and / or substrate limitations. Therefore, it is still a challenging goal to develop an efficient synthesis method of tetrasubstituted furan with flexible substitution configuration. SUMMARY
[0005] The application aims to provide a synthesis method of 2,3-diacyl tetrasubstituted furan. The method has the advantages of cheap and readily available raw materials, simple operation, mild conditions and wide substrate range, and provides a new way for the synthesis of diacyl tetrasubstituted furan.
[0006] The synthesis method of 2,3-diacyl tetrasubstituted furan of the application is to use terminal aryl alkyne 1 and 1,2-diketone 2 as raw materials, and to obtain 2,3-diacyl tetrasubstituted furan 3 through addition cyclization isomerization reaction.
[0007] The synthesis route is as follows:
[0008]
[0009] wherein, Ar 1 , Ar 2 is aryl, heteroaryl.
[0010] The substituents on the benzene ring in the aryl group include but are not limited to halogens such as fluorine, chlorine, bromine and iodine, and the substitution positions include one or more different substitutions of ortho, meta and para positions of the benzene ring.
[0011] The heteroaryl group can be 1-naphthyl, 2-thienyl, 3-thienyl, 2-furyl, 3-pyridyl.
[0012] Further, the Ar 1 , Ar 2 is preferably phenyl.
[0013] The synthesis method of the 2,3-diacyl tetra-substituted furan of the present application comprises the following steps:
[0014] The target product is obtained through addition, cyclization and isomerization reaction in the presence of a catalyst, a base and a solvent, with terminal aryl alkyne 1 and 1,2-diketone 2 as raw materials.
[0015] The equivalent ratio of the 1,2-diketone is selected from 0.5, 1.0, 1.5, and the obtained yield is 65%, 75%, 75% respectively, so the preferred equivalent ratio is 1.0.
[0016] The catalyst is selected from one of Cu(OAc)2·H2O, CuBr2, CuCl, CuBr, CuI, Pd(OAc)2, PdCl2, Ag2CO3, and the yield obtained by the above different catalysts is 75%, 66%, 45%, 40%, 20%, 0%, 0%, 0% respectively, so the preferred catalyst is AgCO3.
[0017] The equivalent ratio of the Cu(OAc)2·H2O is selected from 5% mol, 10% mol, 20% mol, and the obtained yield is 75%, 73%, 75% respectively, so the preferred equivalent ratio is 5% mol.
[0018] The base is selected from one of DMAP, Et3N, DBU, DABCO, TMG, K2CO3, Na2CO3, KOH, KOAc, and the yield obtained by the above different bases is 75%, 0%, 0%, 10%, 23%, 0%, 0%, 0%, 0% respectively, so the preferred base is DMAP.
[0019] The equivalent ratio of the DMAP is selected from 0.5, 1.0, 1.5, 2.0 equivalents, and the obtained yield is 45%, 75%, 75%, 74% respectively, so the preferred equivalent ratio is 1.0 equivalent.
[0020] Further, the molar ratio of aryl alkyne 1, 1,2-diketone 2, Cu(OAc)2·H2O and DMAP is 1:1:0.05:1.
[0021] The solvent is one of dimethyl sulfoxide, N,N-dimethylformamide, toluene, acetonitrile, tetrahydrofuran, dichloromethane, 1,4-dioxane, and the obtained yield is 75%, 25%, 10%, 0%, 0%, 0%, 0% respectively, so the preferred solvent is dimethyl sulfoxide.
[0022] The concentration of the aryl alkyne 1 in dimethyl sulfoxide is 0.1 M.
[0023] The reaction temperature is selected from 80℃, 90℃, 100℃, 110℃, and the obtained yield is 45%, 63%, 75%, 74% respectively, and thus 100℃ is preferred.
[0024] The reaction time is selected from 24, 48, 72, 96 hours, and the obtained yield is 45%, 67%, 75%, 75% respectively, and thus 72 hours is preferred.
[0025] Further, the molar ratio of the aryl alkyne 1, the 1,2-diketone 2, Cu(OAc)2·H2O and DMAP is 1:1:0.05:1, the reaction solvent is dimethyl sulfoxide, the reaction temperature is 100℃, and the reaction time is 72 hours.
[0026] The separation and purification is that the crude product is extracted and separated with ethyl acetate and water, concentrated, and then column chromatography separation and purification is performed with ethyl acetate / petroleum ether with a volume ratio of 1:10 as the eluent.
[0027] Compared with the prior art, the method has the advantages of cheap and easy-to-obtain raw materials, simple operation, mild conditions, wide substrate range, etc., and provides a novel approach for the synthesis of diacyl tetrasubstituted furan. BRIEF DESCRIPTION OF DRAWINGS
[0028] Figure 1 Nuclear magnetic resonance hydrogen spectrum of the 2,3-diacyl tetrasubstituted furan 3aa synthesized in Example 1.
[0029] Figure 2 Nuclear magnetic resonance carbon spectrum of the 2,3-diacyl tetrasubstituted furan 3ba synthesized in Example 2.
[0030] Figure 3 Nuclear magnetic resonance carbon spectrum of the 2,3-diacyl tetrasubstituted furan 3ab synthesized in Example 3.
[0031] Figure 4 Nuclear magnetic resonance carbon spectrum of the 2,3-diacyl tetrasubstituted furan 3ac synthesized in Example 4.
[0032] Figure 5 XRD single crystal diffraction pattern of the 2,3-diacyl tetrasubstituted furan 3ba synthesized in Example 2. DETAILED DESCRIPTION
[0033] The technical solutions of the present application are further analyzed and described below through specific examples.
[0034] Example 1:
[0035] Phenylacetylene (0.5 mmol), 1,2-diphenyl-1,2-dione (0.5 mmol), Cu(OAc)2.H2O (0.05 mmol), DMAP (0.5 mmol) were added to a 15 mL flask, then 5 mL of dimethyl sulfoxide was added, and the reaction was stirred at 100 °C oil bath for 72 hours, after the end, washed with water, extracted with ethyl acetate, dried under reduced pressure, the crude product was separated by flash column chromatography with ethyl acetate / petroleum ether (1:3) to obtain 2,3-diacyl tetra-substituted furan 3aa yellow solid product with 75% yield.
[0036] The reaction scheme of this step is shown below:
[0037]
[0038] The product was characterized by the following data: Yellow solid; m.p. 106-107 °C; 1 H NMR (400 MHz, CDC13) δ 8.12 (d, J = 7.3 Hz, 2H), 7.87 (d, J = 7.3 Hz, 2H), 7.61 - 7.53 (m, 3H), 7.52 - 7.45 (m, 3H), 7.39 - 7.24 (m, 10H). 13 C NMR (100 MHz, CDC13) δ 191.6, 181.2, 152.5, 147.8, 137.1, 136.4, 135.9, 133.6, 133.0, 130.7, 129.9, 129.7, 129.4, 129.2, 128.9, 128.8, 128.6, 128.5, 128.4, 126.9, 124.6. HRMS m / z (APCI) calcd for C 30 H 21 O3 (M+H) + 429.1485 found 429.1483.
[0039] Example 2:
[0040] M-methylphenylacetylene (0.5 mmol), 1,2-diphenyl-1,2-dione (0.5 mmol), Cu(OAc)2.H2O (0.05 mmol), DMAP (0.5 mmol) were added to a 15 mL flask, then 5 mL of dimethyl sulfoxide was added, and the reaction was stirred at 100 °C oil bath for 72 hours, after the end, washed with water, extracted with ethyl acetate, dried under reduced pressure, the crude product was separated by flash column chromatography with ethyl acetate / petroleum ether (1:3) to obtain 2,3-diacyl tetra-substituted furan 3ba yellow solid product with 63% yield.
[0041] The reaction scheme for this step is shown below:
[0042]
[0043] The product characterization data results are: Yellow solid; m.p. 102-103 °C; 1 HNMR (400 MHz, CDC13) δ 7.95 - 7.91 (m, 1H), 7.85 - 7.83 (m, 3H), 7.60 - 7.55 (m, 2H), 7.52 - 7.46 (m, 1H), 7.39 - 7.32 (m, 7H), 7.20 - 7.07 (m, 4H), 2.39 (s, 3H), 2.24 (s, 3H). 13 C NMR (100 MHz, CDC13) δ 191.5, 181.5, 152.3, 147.8, 138.5, 138.3, 137.3, 136.5, 135.8, 133.7, 133.4, 130.6, 130.29, 129.3, 129.3, 129.2, 129.1, 128.7, 128.5, 128.3, 127.0, 126.8, 126.7, 124.7, 21.4, 21.4. HRMS m / z (APCI) calcd for C 32 H 25 O3 (M+H)+ 457.1798 found 457.1794.
[0044] Example 3:
[0045] Phenylacetylene (0.5 mmol), 1,2-di(4-methylphenyl)-1,2-dione (0.5 mmol), Cu(OAc)2.H2O (0.05 mmol), DMAP (0.5 mmol) were added to a 15 mL flask, then 5 mL of dimethyl sulfoxide was added, and the reaction was stirred at 100 °C oil bath for 72 hours, after completion, washed with water, extracted with ethyl acetate, dried under reduced pressure, and the crude product was separated by flash column chromatography with ethyl acetate / petroleum ether (1:3) to obtain 2,3-diacyl tetra-substituted furan 3ab yellow solid product with a yield of 66%.
[0046] The reaction scheme for this step is shown below:
[0047]
[0048] The product characterization data results are: Yellow solid; m.p. 102-103 °C; 1HNMR (400 MHz, CDC13) δ 8.12 (d, J = 7.9 Hz, 2H), 7.77 (d, J = 8.1 Hz, 2H), 7.57 (t, J = 7.4 Hz, 1H), 7.49 - 7.43 (m, 4H), 7.33 - 7.22 (m, 5H), 7.17 - 7.12 (m, 4H), 2.35 (d, J = 2.3 Hz, 6H). 13 C NMR (100 MHz, CDC13) δ 191.2, 181.1, 152.8, 147.5, 144.5, 139.6, 136.5, 136.2, 134.8, 132.8, 130.9, 129.8, 129.7, 129.5, 129.3, 128.8, 128.4, 128.2, 126.9, 126.5, 124.0, 21.8, 21.5. HRMS m / z (APCI) calcd for C 32 H 25 O3 (M+H) +
[0049] 457.1798 found 457.1796.
[0050] Example 4:
[0051] Benzaldehyde (0.5 mmol), 1,2-di(4-chlorophenyl)-1,2-dione (0.5 mmol), Cu(OAc)2.H2O (0.05 mmol), DMAP (0.5 mmol) were added into a 15 mL flask, then 5 mL of dimethyl sulfoxide was added, and the reaction was stirred at 100 °C oil bath for 72 hours. After completion, water was added for washing, and ethyl acetate was used for extraction, dried under reduced pressure, and the crude product was separated by flash column chromatography with ethyl acetate / petroleum ether (1:3) to obtain 2,3-diacyl tetra-substituted furan 3ac yellow solid product with a yield of 77%.
[0052] The reaction formula of this step is as follows:
[0053]
[0054] The product characterization data results are: Yellow solid; m.p. 104-105 °C; 1 HNMR (400 MHz, CDC13) δ 8.12 (d, J = 7.9 Hz, 2H), 7.77 (d, J = 8.1 Hz, 2H), 7.57 (t, J = 7.4 Hz, 1H), 7.49 - 7.43 (m, 4H), 7.33 - 7.22 (m, 5H), 7.17 - 7.12 (m, 4H), 2.35 (d, J = 2.3 Hz, 6H). 13C NMR (100 MHz, CDC13) δ 190.0, 181.1, 151.5, 148.0, 140.1, 136.1, 135.5, 135.4, 135.4, 133.2, 130.5, 130.2, 129.8, 129.5, 129.2, 129.1, 129.0, 128.7, 128.6, 128.1, 127.5, 124.8. HRMS m / z (APCI) calculated for C 30 H 19 Cl2O3 (M+H) + 497.0705 found 497.0703.
[0055] The above reference examples, which describe in detail a method for synthesizing 2,3-diacyl polysubstituted furan, are illustrative rather than limiting, and a number of embodiments can be listed within the scope defined, so that variations and modifications that do not depart from the general idea of the present application should be within the scope of protection of the present application.
Claims
1. A method for synthesizing 2, 3-diacyl tetra-substituted furan, characterized in that: a target product 3-2, 3-diacyl tetra-substituted furan is obtained through an addition-cyclization-isomerization reaction in the presence of a catalyst, a base and a solvent, with compound 1-aryl end alkyne and compound 2-1, 2-diketone as raw materials; the synthesis route is as shown below: ； wherein Ar 1 , Ar 2 is selected from aryl; The catalyst is Cu(OAc)2 . H2O.
2. The method according to claim 1, characterized in that: the substituents on the benzene ring of the aryl group include but are not limited to fluorine, chlorine, bromine or iodine, and the substitution positions include one or more different substitutions at the ortho, meta and para positions of the benzene ring.
3. The method according to claim 1, characterized in that: Ar 1 , Ar 2 is phenyl.
4. The method according to claim 1, characterized in that: the equivalent ratio of the compound 2 is 0.5-1.5, based on the compound 1.
5. The method according to claim 1, characterized in that: the equivalent ratio of the catalyst is 5% mol to 20% mol.
6. The method according to claim 1, characterized in that: the base is selected from one of DMAP, Et3N, DBU, DABCO, TMG, K2CO3, Na2CO3, KOH, KOAc, and the equivalent ratio of the base is 0.5 to 2.0 equivalents.
7. The method according to claim 1, characterized in that: the solvent is one of dimethyl sulfoxide, N, N-dimethylformamide, toluene, acetonitrile, tetrahydrofuran, dichloromethane and 1, 4-dioxane.
8. The method according to claim 1, characterized in that: the reaction temperature is 80-110°C, and the reaction time is 24-96 hours.