Synthesis method of 2, 3-diacyl tetra-substituted furan

Abstract

The invention discloses a synthesis method of 2, 3-diacyl tetra-substituted furan, terminal aryne 1 and 1, 2-diketone 2 are used as raw materials, 2, 3-diacyl tetra-substituted furan 3 is obtained through addition cyclization isomerization reaction, and the synthesis route is as follows: # imgabs0 #. The method has the advantages of cheap and easily available raw materials, simple operation, mild conditions, wide substrate range and the like; and a brand new way is provided for synthesis of diacyl tetra-substituted furan.

Description

Technical Field

[0001] The invention belongs to the technical field of organic compound synthesis, and particularly relates to a method for synthesizing 2,3-diacyl tetrasubstituted furan. Background Art

[0002] Polysubstituted furans are important components of many biologically active natural products, drugs and functional materials. Furan compounds can also be used as important components of organic synthesis. In the past few decades, chemists have paid extensive attention and efforts to the synthesis of polysubstituted furans and designed various excellent synthetic strategies for the construction of tetrasubstituted furans.

[0003]

[0004] At present, there are four main strategies for the synthesis of tetrasubstituted furans: 1) cycloisomerization of allenes and enynols, ketones and their derivatives; 2) tandem cycloaddition reactions of functionalized alkenes, alkynes, allenes and carbonyl compounds; 3) three-component tandem reactions of terminal alkynes with aldehydes, nitriles or acyl compounds; 4) cycloaddition reactions of transition metal-catalyzed activated alkenes with allenyl esters. These methods have made great progress in the construction of tetrasubstituted furan skeletons, but there are still complex operations and / or substrate limitations. Therefore, the development of efficient synthetic methods for tetrasubstituted furans with flexible substituent configurations remains a challenging goal. Summary of the invention

[0005] The present invention aims to provide a method for synthesizing 2,3-diacyl tetrasubstituted furans. The method of the present invention has the advantages of cheap and readily available raw materials, simple operation, mild conditions, and a wide range of substrates, and provides a new approach for the synthesis of diacyl tetrasubstituted furans.

[0006] The method for synthesizing 2,3-diacyl tetrasubstituted furan of the present invention uses terminal aromatic alkyne 1 and 1,2-diketone 2 as raw materials, and obtains 2,3-diacyl tetrasubstituted furan 3 through addition cycloisomerization reaction.

[0007] The synthetic route is as follows:

[0008]

[0009] Among them, Ar 1 ,Ar 2 It is an aryl group or a heteroaryl group.

[0010] The substituents on the benzene ring in the aromatic 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 in the ortho, meta, and para positions of the benzene ring.

[0011] The heteroaryl group may be 1-naphthyl, 2-thienyl, 3-thienyl, 2-furyl, or 3-pyridyl.

[0012] Furthermore, the Ar 1 ,Ar 2 Preferred is phenyl.

[0013] The method for synthesizing 2,3-diacyl tetrasubstituted furan of the present invention comprises the following steps:

[0014] Terminal aromatic acetylene 1 and 1,2-diketone 2 are used as raw materials, and an addition cycloisomerization reaction is carried out in the presence of a catalyst, a base and a solvent to obtain the target product.

[0015] The equivalent ratio of the 1,2-diketone is selected from 0.5, 1.0, and 1.5, and the obtained yields are 65%, 75%, and 75%, respectively, so 1.0 equivalent is preferred.

[0016] The catalyst is selected from one of Cu(OAc)2·H2O, CuBr2, CuCl, CuBr, CuI, Pd(OAc)2, PdCl2, and Ag2CO3. The yields obtained from the above different catalysts are 75%, 66%, 45%, 40%, 20%, 0%, 0%, and 0%, respectively. Therefore, AgCO3 is preferred.

[0017] The equivalent ratio of Cu(OAc)2·H2O is selected from 5% mol, 10% mol, and 20% mol, and the obtained yields are 75%, 73%, and 75%, respectively, so 5% mol is preferred.

[0018] The base is selected from one of DMAP, Et3N, DBU, DABCO, TMG, K2CO3, Na2CO3, KOH, and KOAc, and the yields obtained from the above different bases are 75%, 0%, 0%, 10%, 23%, 0%, 0%, 0%, 0%, and 0%, respectively. Therefore, DMAP is preferred.

[0019] The equivalent ratio of DMAP is selected from 0.5, 1.0, 1.5, and 2.0 equivalents, and the obtained yields are 45%, 75%, 75%, and 74%, respectively, so 1.0 equivalent is preferred.

[0020] Furthermore, the molar ratio of the aryne 1, 1,2-dione 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, and 1,4-dioxane, and the yields obtained are 75%, 25%, 10%, 0%, 0%, 0%, and 0%, respectively, so dimethyl sulfoxide is preferred.

[0022] The concentration of the aryne 1 in dimethyl sulfoxide was 0.1 M.

[0023] The reaction temperature is selected from 80°C, 90°C, 100°C, and 110°C, and the obtained yields are 45%, 63%, 75%, and 74%, respectively, so 100°C is preferred.

[0024] The reaction time is selected from 24, 48, 72, and 96 hours, and the yields obtained are 45%, 67%, 75%, and 75%, respectively, so 72 hours is preferred.

[0025] Furthermore, the molar ratio of aryne 1, 1,2-dione 2, Cu(OAc)2·H2O and DMAP is 1:1:0.05:1, the reaction solvent is dimethyl sulfoxide, the reaction temperature is 100°C, and the reaction time is 72 hours.

[0026] The separation and purification is to extract and separate the crude product with ethyl acetate and water, concentrate it, and then perform column chromatography separation and purification using ethyl acetate / petroleum ether with a volume ratio of 1:10 as an eluent.

[0027] Compared with the existing technology, this method has the advantages of cheap and readily available raw materials, simple operation, mild conditions, and a wide range of substrates, and provides a new approach for the synthesis of diacyl tetrasubstituted furans. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 This is the hydrogen nuclear magnetic resonance spectrum of the 2,3-diacyl tetrasubstituted furan 3aa synthesized in Example 1.

[0029] Figure 2 This is the carbon nuclear magnetic resonance spectrum of 2,3-diacyl tetrasubstituted furan 3ba synthesized in Example 2.

[0030] Figure 3 This is the carbon NMR spectrum of 2,3-diacyl tetrasubstituted furan 3ab synthesized in Example 3.

[0031] Figure 4 This is the carbon NMR spectrum of 2,3-diacyl tetrasubstituted furan 3ac synthesized in Example 4.

[0032] Figure 5 This is the XRD single crystal diffraction pattern of 2,3-diacyltetrasubstituted furan 3ba synthesized in Example 2. DETAILED DESCRIPTION

[0033] The technical solution of the present invention is further analyzed and explained below through specific embodiments.

[0034] Embodiment 1:

[0035] Phenylacetylene (0.5 mmol), 1,2-diphenyl-1,2-dione (0.5 mmol), Cu(OAc)2·H2 (0.05 mmol) and DMAP (0.5 mmol) were added into a 15 mL flask, and then 5 mL of dimethyl sulfoxide was added. The mixture was stirred in an oil bath at 100°C for 72 hours. After the reaction, the mixture was washed with water, extracted with ethyl acetate, and dried under reduced pressure. The crude product was separated by rapid column chromatography with ethyl acetate / petroleum ether in a volume ratio of 1:3 to obtain 2,3-diacyl tetrasubstituted furan 3aa as a yellow solid product with a yield of 75%.

[0036] The reaction formula for this step is as follows:

[0037]

[0038] The characterization data of the product are as follows: Yellow solid; mp106-107℃; 1 H NMR (400MHz, CDCl3) δ8.12(d,J=7.3Hz,2H),7.87(d,J=7.3Hz,2H),7.61–7.53(m,3H),7.52–7.45(m,3H),7.39–7.24(m,10H). 13 C NMR (100MHz, CDCl3) δ191.6,181.2,152.5,147.8,137.1,136.4,135.9,133.6,133.0,13 0.7,129.9,129.7,129.4,129.2,128.9,128.8,128.6,128.5,128.4,126.9,124.6.HRMS m / z(APCI)calcd for C 30 H 21 O3(M+H) + 429.1485 found 429.1483.

[0039] Embodiment 2:

[0040] m-Methylphenylacetylene (0.5mmol), 1,2-diphenyl-1,2-dione (0.5mmol), Cu(OAc)2·H2 (0.05mmol), and DMAP (0.5mmol) were added into a 15mL flask, and then 5mL of dimethyl sulfoxide was added. The mixture was stirred in an oil bath at 100°C for 72 hours. After the reaction, water was added for washing, and the mixture was extracted with ethyl acetate and dried under reduced pressure. The crude product was separated by rapid column chromatography with ethyl acetate / petroleum ether in a volume ratio of 1:3 to obtain 2,3-diacyl tetrasubstituted furan 3ba as a yellow solid product with a yield of 63%.

[0041] The reaction formula for this step is as follows:

[0042]

[0043] The characterization data of the product are as follows: Yellow solid; mp102-103°C; 1 HNMR(400MHz, CDCl3)δ7.95–7.91(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 (100MHz, CDCl3) δ191.5,181.5,152.3,147.8,138.5,138.3,137.3,136.5,135.8,133.7,133.4,130. 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)+457.1798found 457.1794.

[0044] Embodiment 3:

[0045] Phenylacetylene (0.5mmol), 1,2-di(4-methylphenyl)-1,2-dione (0.5mmol), Cu(OAc)2·H2 (0.05mmol), and DMAP (0.5mmol) were added into a 15mL flask, and then 5mL of dimethyl sulfoxide was added. The mixture was stirred in an oil bath at 100°C for 72 hours. After the reaction, the mixture was washed with water, extracted with ethyl acetate, and dried under reduced pressure. The crude product was separated by rapid column chromatography with ethyl acetate / petroleum ether in a volume ratio of 1:3 to obtain 2,3-diacyl tetrasubstituted furan 3ab as a yellow solid product with a yield of 66%.

[0046] The reaction formula for this step is as follows:

[0047]

[0048] The characterization data of the product are as follows: Yellow solid; mp89-90℃; 1HNMR (400MHz, CDCl3) δ8.12(d,J=7.9Hz,2H),7.77(d,J=8.1Hz,2H),7.57(t,J=7.4Hz ,1H),7.49–7.43(m,4H),7.33–7.22(m,5H),7.17–7.12(m,4H),2.35(d,J=2.3Hz,6H). 13 C NMR (100MHz, CDCl3) δ191.2,181.1,152.8,147.5,144.5,139.6,136.5,136.2,134.8,132.8,1 30.9,129.8,129.7,129.5,129.3,128.8,128.4,128.2,126.9,126.5,124.0,21.8,21.5.HRMS m / z(APCI)calcdfor C 32 H 25 O3(M+H) +

[0049] 457.1798 found 457.1796.

[0050] Embodiment 4:

[0051] Phenylacetylene (0.5mmol), 1,2-bis(4-chlorophenyl)-1,2-dione (0.5mmol), Cu(OAc)2·H2 (0.05mmol), and DMAP (0.5mmol) were added into a 15mL flask, and then 5mL of dimethyl sulfoxide was added. The mixture was stirred in an oil bath at 100°C for 72 hours. After the reaction, the mixture was washed with water, extracted with ethyl acetate, and dried under reduced pressure. The crude product was separated by rapid column chromatography with ethyl acetate / petroleum ether in a volume ratio of 1:3 to obtain 2,3-diacyl tetrasubstituted furan 3ac as a yellow solid product with a yield of 77%.

[0052] The reaction formula for this step is as follows:

[0053]

[0054] The characterization data of the product are as follows: Yellow solid; mp104-105°C; 1 HNMR (400MHz, CDCl3) δ8.12–8.05(m,2H),7.79(d,J=8.6Hz,2H),7.60(t,J=7.4Hz,1H),7.52-7.46(m,4H),7.37–7.23(m,10H). 13C NMR (100MHz, CDCl3) δ190.0,181.1,151.5,148.0,140.1,136.1,135.5,135.4,135.4,133.2 ,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 provide a detailed description of a method for synthesizing 2,3-diacyl polysubstituted furans, which is illustrative rather than restrictive, and several embodiments can be listed according to the limited scope. Therefore, changes and modifications without departing from the overall concept of the present invention should fall within the scope of protection of the present invention.

Claims

1. A method for synthesizing 2,3-diacyl tetrasubstituted furan, characterized in that: Using terminal aryl acetylene 1 and 1,2-diketone 2 as raw materials, 2,3-diacyl tetrasubstituted furan 3 was obtained through addition cycloisomerization reaction; The synthetic route is as follows: Among them, Ar 1 ,Ar 2 is selected from aryl or heteroaryl.

2. The synthesis method according to claim 1, characterized in that: The substituents on the benzene ring in the aryl group include but are not limited to fluorine, chlorine, bromine or iodine, and the substitution positions include one or more different substitutions in the ortho, meta and para positions of the benzene ring.

3. The synthesis method according to claim 1, characterized in that: The heteroaryl group is 1-naphthyl, 2-thienyl, 3-thienyl, 2-furyl or 3-pyridyl.

4. The synthesis method according to claim 1, characterized in that: The Ar 1 ,Ar 2 It is phenyl.

5. The synthesis method according to claim 1, characterized in that The following steps are involved: Terminal aromatic acetylene 1 and 1,2-diketone 2 are used as raw materials, and an addition cycloisomerization reaction is carried out in the presence of a catalyst, a base and a solvent to obtain the target product.

6. The synthesis method according to claim 1, characterized in that: The equivalent ratio of the 1,2-diketone 2 is 0.5-1.5, based on the terminal aryl alkyne 1.

7. The synthesis method according to claim 1, characterized in that: The catalyst is selected from Cu(OAc) 2. One of H2O, CuBr2, CuCl, CuBr, CuI, Pd(OAc)2, PdCl2, and Ag2CO3, wherein the equivalent ratio of the catalyst is 5% mol to 20% mol.

8. The synthesis method according to claim 1, characterized in that: The base is selected from one of DMAP, Et3N, DBU, DABCO, TMG, K2CO3, Na2CO3, KOH, and KOAc, and the equivalent ratio of the base is 0.5 to 2.0 equivalents.

9. The synthesis 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.

10. The synthesis method according to claim 1, characterized in that: The reaction temperature is 80°C to 110°C, and the reaction time is 24 to 96 hours.

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