CN109053649B - Method for preparing 2, 5-disubstituted furan compound - Google Patents
Method for preparing 2, 5-disubstituted furan compound Download PDFInfo
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- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
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Abstract
The invention discloses a method for preparing 2, 5-disubstituted furan compounds, which comprises the following steps: adding RCHO, 2-acyl furan, an initiator and a catalyst into an organic solvent, and performing reflux reaction to obtain a 2, 5-disubstituted furan compound; wherein the molar ratio of RCHO to 2-acylfuran is 100: 1-1: 100, respectively; the molar ratio of RCHO to initiator is 100: 1-1: 100; the molar ratio of RCHO to catalyst is 100: 1-1: 100. the method for preparing the 2, 5-disubstituted furan compounds does not need strict anhydrous conditions, does not need strong alkali, and has the advantages of simple and convenient operation, low cost and the like.
Description
Technical Field
The invention relates to a preparation method of a polysubstituted furan compound, in particular to a method for preparing a 2, 5-disubstituted furan compound.
Background
Furan rings, a representative of five-membered heterocycles, are widely found in natural products and continue to attract attention from the organic synthesis community because of their inherent biological activity. Recent studies have shown that polysubstituted furan compounds have good effects in the aspects of antivirus, antibacterium, antitumor, anti-inflammatory, insecticidal and the like. The polysubstituted furan is not only a structural unit of a natural product and an important drug, but also an important intermediate of organic synthesis, and is applied to raw materials of pesticides, medicines, perfumes and dyes.
At present, the most classical method for synthesizing 2, 5-disubstituted furans is condensation cyclization synthesis (Paal-Knoor reaction) by adopting 1, 4-dicarbonyl compounds, but the step for synthesizing the 1, 4-dicarbonyl compounds with slightly complex structures is long and the cost is high. Or olefin and alkyne are taken as substrates, and cyclization reaction is catalyzed by transition metal, and the method needs transition metal catalysis, so the reaction condition is relatively harsh, and the synthesis cost is high. The furan and the derivatives thereof are used as deep processing products of some crops, belong to renewable resources and are low in price. Therefore, the method of obtaining 2, 5-difuran by using reproducible furan as a raw material and modifying the structure of furan ring is a good method. The most reported methods for synthesizing 2, 5-disubstituted bark furan by using furan compounds as raw materials are that furfural which is cheap and easy to obtain and derivatives thereof are used as raw materials, and a group is introduced into the other alpha position of a furan ring to realize the synthesis of the 2, 5-disubstituted bark furan compounds. However, the introduction of an alkyl group in the α -position is generally achieved by reacting an alkyl halide with a furan anion formed by using butyl lithium or a grignard reagent as a strong base, which requires improvement in terms of cost or operation steps. In addition, especially when one alpha position of furan contains a carbonyl substituent, the formation of furan anions at the other alpha position by using butyl lithium or Grignard reagent as a strong base becomes impossible, so that the invention of a method for introducing an alkyl group into the other alpha position of furan ring to generate 2, 5-disubstituted bark when the alpha position of furan contains a carbonyl substituent is urgently needed.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention aims to provide the method for preparing the 2, 5-disubstituted furan compound, which does not need strict anhydrous conditions, does not need strong alkali, and has the advantages of simple and convenient operation, low cost and the like.
The purpose of the invention is realized by the following technical scheme:
a method of preparing a 2, 5-disubstituted furan compound comprising the steps of:
RCHO, reaction of,
Adding an initiator and a catalyst into an organic solvent, and performing reflux reaction to obtain
Wherein RCHO and
in a molar ratio of 100: 1-1: 100, respectively; the molar ratio of RCHO to initiator is 100: 1-1: 100, respectively; the molar ratio of RCHO to catalyst is 100: 1-1: 100;
wherein R is saturated aliphatic hydrocarbon or alicyclic hydrocarbon of C1-C12;
x is H, OR 1 Wherein R is 1 Is hydrogen, saturated aliphatic hydrocarbon of C1-C6 or
R 2 Is hydrogen, an electron donating group or an electron withdrawing group;
or X is NR 3 R 4 In which R is 3 、R 4 Is hydrogen, saturated aliphatic hydrocarbon of C1-C6 or
R 5 Hydrogen, an electron donating group or an electron withdrawing group.
Preferably, the electron-donating group is OH or CH 3 、OCH 3 、OC 2 H 5 、N(CH 3 ) 2 Or N (C) 2 H 5 ) 2 。
Preferably, the electron-withdrawing group is Cl, Br, F, NO 2 CN or CF 3 。
Preferably, the reaction temperature of the reflux reaction is 0-160 ℃, and the reaction time is 1-60 hours.
Preferably, the organic solvent is at least one of benzene, toluene, xylene, mesitylene, chlorobenzene, o-dichlorobenzene, m-dichlorobenzene, p-dichlorobenzene, fluorobenzene, pentafluorobenzene, hexafluorobenzene, ethyl acetate, tert-butyl acetate, propyl acetate, acetonitrile, benzonitrile, tetrahydrofuran, diethyl ether and 1, 4-dioxane.
Preferably, the initiator is at least one of azodiisobutyronitrile, benzoyl peroxide, t-butyl peroxide, acetyl peroxide and di-t-butyl peroxide.
Preferably, the catalyst is Fe (OAc) 2 、Cu(OAc) 2 、Co(OAc) 2、 Mn(OAc) 2 、Pd(OAc) 2 、Ni(acac) 2 、Fe(acac) 2 、Fe(OTf) 2 、FeCl 2 、Fe(acac) 3、 Fe(OTf) 3、 FeCl 3 、FeCl 2 At least one of (1).
Preferably, the 2, 5-disubstituted furans have the following structure:
compared with the prior art, the invention has the following advantages and beneficial effects:
(1) the alkylating agent used in the invention does not need halogenated hydrocarbon, and uses fatty aldehyde as the alkylating agent;
(2) the method does not need strict anhydrous condition and low-temperature operation, does not need expensive strong alkali such as butyl lithium, and has simple operation and low cost.
Detailed Description
The present invention will be described in further detail with reference to examples, but the embodiments of the present invention are not limited thereto.
Example 1
A polysubstituted furan compound is prepared by the following steps:
adding 50-80 mL of chlorobenzene into a 250mL single-neck flask, and then adding 10mmol of tert-butyl aldehyde and 10mmol of tert-butyl aldehyde
Reflux reaction at 100 deg.c for 12 hr, decompression eliminating solvent to obtain coarse product, and fast column chromatographic separation to obtain the product
41.6mg (81%). The structure of the product characterizes the physical constants: 1 H NMR(400MHz,CDCl 3 )δ7.42-7.34(m,2H),7.31-7.27(m,1H),7.21-7.18(m,2H),6.53(d,J＝3.4Hz,1H),5.85(d,J＝3.4Hz,1H),3.41(s,3H),0.97(s,9H)； 13 C NMR(100MHz,CDCl 3 )δ166.57,159.66,145.92,144.91,129.43,127.27,127.19,117.85,103.84,38.61,32.70,28.55.
example 2
Adding 50-80 mL of chlorobenzene into a 250mL single-neck flask, and then adding 10mmol of tert-butyl aldehyde and 10mmol of tert-butyl aldehyde
Reflux reaction at 100 deg.c for 12 hr, decompression eliminating solvent to obtain coarse product, and fast column chromatographic separation to obtain the product
28.8mg (74%). The structure of the product characterizes the physical constants: 1 H NMR(400MHz,CDCl 3 )δ6.93(d,J＝3.4Hz,1H),6.06(d,J＝3.4Hz,1H),3.19(br,6H),1.30(s,9H)； 13 C NMR(100MHz,CDCl 3 )δ166.12,160.71,146.55,117.33,104.09,32.98,29.04.
example 3
Adding 50-80 mL of chlorobenzene into a 250mL single-neck flask, and then adding 10mmol of tert-butyl aldehyde and 10mmol of tert-butyl aldehyde
Reflux reaction at 100 deg.c for 12 hr, decompression eliminating solvent to obtain coarse product, and fast column chromatographic separation to obtain the product
33.4mg (75%). The structure of the product characterizes the physical constants: 1 H NMR(400MHz,CDCl 3 )δ6.97(d,J＝3.4Hz,1H),6.05(d,J＝3.4Hz,1H),3.56(br,4H),1.30(s,9H),1.25(br,6H)； 13 C NMR(100MHz,CDCl 3 )δ165.84,159.80,147.09,117.34,104.15,32.94,29.05.
example 4
Adding 50-80 mL of chlorobenzene into a 250mL single-neck flask, and then adding 10mmol of tert-butyl aldehyde and 10mmol of tert-butyl aldehyde
Reflux reaction at 100 deg.c for 12 hr, decompression eliminating solvent to obtain coarse product, and fast column chromatographic separation to obtain the product
46.2mg (69%). The structure of the product characterizes the physical constants: 1 H NMR(400MHz,CDCl 3 )δ7.68(dd,J＝8.0,1.2Hz,1H),7.35(td,J＝8.0,1.2Hz,1H),7.29-7.25(m,1H),7.24-7.19(m,1H),6.70(d,J＝3.4Hz,1H),5.88(d,J＝3.4Hz,1H),3.33(s,3H),0.96(s,9H)； 13 C NMR(100MHz,CDCl 3 )δ166.85,159.32,145.98,143.74,133.69,129.95,129.39,128.67,123.60,118.07,104.05,37.27,32.78,28.50.
example 5
Adding 50-80 mL of chlorobenzene into a 250mL single-neck flask, and then adding10mmol of tert-butylaldehyde and 10mmol of
Reflux reaction at 100 deg.c for 12 hr, decompression eliminating solvent to obtain coarse product, and fast column chromatographic separation to obtain the product
44.7mg (78%). The structure of the product characterizes the physical constants: 1 H NMR(400MHz,CDCl 3 )δ7.27(t,J＝8.0Hz,1H),6.84(d,J＝8.4Hz,1H),6.79(d,J＝8.0Hz,1H),6.73(s,1H),6.56(d,J＝3.4Hz,1H),5.87(d,J＝3.4Hz,1H),3.76(s,3H),3.40(s,3H),1.00(s,9H)； 13 C NMR(100MHz,CDCl 3 )δ166.58,160.50,159.63,146.01,145.88,130.04,119.45,117.83,113.06,112.98,103.89,55.46,38.53,32.74,28.58.
example 6
Adding 50-80 mL of chlorobenzene into a 250mL single-neck flask, and then adding 10mmol of tert-butyl aldehyde and 10mmol of tert-butyl aldehyde
Reflux reaction at 100 deg.c for 12 hr, decompression eliminating solvent to obtain coarse product, and fast column chromatographic separation to obtain the product
34.9mg (79%). The structure of the product characterizes the physical constants: 1 H NMR(400MHz,CDCl 3 )δ7.00(d,J＝3.4Hz,1H),6.07(d,J＝3.4Hz,1H),3.86(t,J＝6.8Hz,2H),3.64(t,J＝6.8Hz,2H),2.05-1.94(m,2H),1.92-1.83(m,2H),1.31(s,9H)； 13 C NMR(100MHz,CDCl 3 )δ166.18,158.43,147.07,116.78,104.15,47.70,46.98,32.92,28.92,26.74,23.77.
example 7
Adding 50-80 mL of chlorobenzene into a 250mL single-neck flask, and then adding 10mmol of tert-butyl aldehyde and 10mmol of tert-butyl aldehyde
Reflux reaction at 100 deg.c for 12 hr, decompression to eliminate solvent to obtain coarse product, and final reactionSeparating with rapid column chromatography to obtain product
36.6mg (79%). The structure of the product characterizes the physical constants: 1 H NMR(400MHz,CDCl 3 )δ6.86(d,J＝3.4Hz,1H),6.04(d,J＝3.4Hz,1H),3.72-3.64(m,4H),1.75-1.58(m,6H),1.30(s,9H)； 13 C NMR(100MHz,CDCl 3 )δ165.60,159.58,146.51,116.71,103.93,32.90,29.05,24.88.
example 8
Adding 50-80 mL of chlorobenzene into a 250mL single-neck flask, and then adding 10mmol of tert-butyl aldehyde and 10mmol of tert-butyl aldehyde
Reflux reaction at 100 deg.c for 12 hr, decompression eliminating solvent to obtain coarse product, and fast column chromatographic separation to obtain the product
25.7mg (61%). The structure of the product characterizes the physical constants: 1 H NMR(400MHz,CDCl 3 )δ7.06(d,J＝3.4Hz,1H),6.10(d,J＝3.4Hz,1H),3.78(s,3H),3.33(s,3H),1.33(s,9H)； 13 C NMR(100MHz,CDCl 3 )δ167.57,159.76,144.29,118.76,104.57,61.50,33.46,33.11,29.04.
example 9
Adding 50-80 mL of chlorobenzene into a 250mL single-neck flask, and then adding 10mmol of tert-butyl aldehyde and 10mmol of tert-butyl aldehyde
Reflux reaction at 100 deg.c for 12 hr, decompression eliminating solvent to obtain coarse product, and fast column chromatographic separation to obtain the product
20.7mg (53%). The structure of the product characterizes the physical constants: 1 H NMR(400MHz,CDCl 3 )δ7.06(d,J＝3.4Hz,1H),6.09(d,J＝3.4Hz,1H),4.33(q,J＝7.2Hz,2H),1.37(d,J＝7.2Hz,3H),1.32(s,9H)； 13 C NMR(100MHz,CDCl 3 )δ168.94,159.11,143.12,118.80,104.74,60.63,33.21,28.95,14.50.
example 9
Adding 50-80 mL of chlorobenzene into a 250mL single-neck flask, and then adding 10mmol of tert-butyl aldehyde and 10mmol of tert-butyl aldehyde
Reflux reaction at 100 deg.c for 12 hr, decompression eliminating solvent to obtain coarse product, and fast column chromatographic separation to obtain the product
20.7mg (53%). The structure of the product characterizes the physical constants: 1 H NMR(400MHz,CDCl 3 )δ7.06(d,J＝3.4Hz,1H),6.09(d,J＝3.4Hz,1H),4.33(q,J＝7.2Hz,2H),1.37(d,J＝7.2Hz,3H),1.32(s,9H)； 13 C NMR(100MHz,CDCl 3 )δ168.94,159.11,143.12,118.80,104.74,60.63,33.21,28.95,14.50.
example 10
Adding 50-80 mL of chlorobenzene into a 250mL single-neck flask, and then adding 10mmol of tert-butyl aldehyde and 10mmol of tert-butyl aldehyde
Reflux reaction at 100 deg.c for 12 hr, decompression eliminating solvent to obtain coarse product, and fast column chromatographic separation to obtain the product
13.3mg (44%). Structural characterization physical constants of the product 1 H NMR(400MHz,CDCl 3 )δ9.54(s,1H),7.16(d,J＝3.4Hz,1H),6.22(d,J＝3.4Hz,1H),1.35(s,9H)； 13 C NMR(100MHz,CDCl 3 )δ177.36,171.54,151.83,106.03,33.47,28.85.
Example 11
Adding 50-80 mL of chlorobenzene into a 250mL single-neck flask, and then adding 10mmol of chlorobenzene
And 10mmol of
Reflux reaction at 100 deg.c for 12 hr, decompression eliminating solvent to obtain coarse product, and fast column chromatographic separation to obtain the product
45.1mg (76%). Structural characterization physical constants of the product 1 H NMR(400MHz,CDCl 3 )δ7.40-7.34(m,2H),7.29(d,J＝7.2Hz,1H),7.21-7.16(m,2H),6.60(d,J＝3.4Hz,1H),5.89(d,J＝3.4Hz,1H),3.40(s,3H),1.56-1.49(m,2H),1.40-1.12(m,8H),0.88(s,3H)； 13 C NMR(100MHz,CDCl 3 )δ165.74,159.71,145.81,144.99,129.44,127.18,127.14,117.93,105.30,38.66,36.47,36.16,25.94,22.46.
Example 12
Adding 50-80 mL of chlorobenzene into a 250mL single-neck flask, and then adding 10mmol of chlorobenzene
And 10mmol of
Reflux reaction at 100 deg.c for 12 hr, decompression eliminating solvent to obtain coarse product, and fast column chromatographic separation to obtain the product
33.4mg (65%). Structural characterization physical constants of the product 1 H NMR(400MHz,CDCl 3 )δ7.41-7.35(m,2H),7.33-7.28(m,1H),7.21-7.17(m,2H),6.25(d,J＝3.4Hz,1H),5.84(d,J＝3.4Hz,1H),3.41(s,3H),2.55-2.45(m,1H),1.42-1.24(m,2H),0.97(d,J＝7.0Hz,3H),0.71(t,J＝7.4Hz,3H)； 13 C NMR(100MHz,CDCl 3 )δ163.04,159.74,145.79,144.81,129.48,127.42,127.34,117.77,105.72,38.58,34.80,28.13,18.18,11.50.
Example 13
Adding 50-80 mL of chlorobenzene into a 250mL single-neck flask, and then adding 10mmol of chlorobenzene
And 10mmol of
Reflux reaction at 100 deg.c for 12 hr, decompression eliminating solvent to obtain coarse product, and fast column chromatographic separation to obtain the product
37.9mg (67%). Structural characterization physical constants of the product 1 H NMR(400MHz,CDCl 3 )δ7.41-7.35(m,2H),7.34-7.29(m,1H),7.21-7.16(m,2H),6.13(d,J＝3.4Hz,1H),5.81(d,J＝3.4Hz,1H),3.41(s,3H),2.46-2.37(m,1H),1.75-1.60(m,4H),1.30–1.05(m,6H)； 13 C NMR(100MHz,CDCl 3 )δ163.29,159.73,145.49,144.81,129.52,127.44,117.79,104.82,38.58,37.20,31.03,26.00,25.79.
Example 14
Adding 50-80 mL of chlorobenzene into a 250mL single-neck flask, and then adding 10mmol of chlorobenzene
And 10mmol of
Reflux reaction at 100 deg.c for 12 hr, decompression eliminating solvent to obtain coarse product, and fast column chromatographic separation to obtain the product
30.9mg (57%). Structural characterization physical constants of the product 1 H NMR(400MHz,CDCl 3 )δ7.41-7.35(m,2H),7.33-7.28(m,1H),7.21-7.17(m,2H),6.27(d,J＝3.4Hz,1H),5.83(d,J＝3.4Hz,1H),3.41(s,3H),2.63-2.53(m,1H),1.38-1.07(m,4H),0.97(d,J＝7.0Hz,3H),0.81(t,J＝7.2Hz,3H)； 13 C NMR(100MHz,CDCl 3 )δ163.31,159.75,145.77,144.83,129.49,127.46,127.37,117.83,105.54,38.61,37.47,33.07,20.26,18.69,14.03.
Example 15
Adding 50-80 mL of chlorobenzene into a 250mL single-neck flask, and then adding 10mmol of chlorobenzene
And 10mmol of
Reflux reaction at 100 deg.c for 12 hr, decompression eliminating solvent to obtain coarse product, and fast column chromatographic separation to obtain the product
35.7mg (66%). The structure of the product characterizes the physical constants: 1 H NMR(400MHz,CDCl 3 )δ7.40-7.34(m,2H),7.31(d,J＝7.0Hz,1H),7.21-7.17(m,2H),6.36(d,J＝3.4Hz,1H),5.87(d,J＝3.4Hz,1H),3.41(s,3H),2.31-2.23(m,1H),1.44-1.16(m,4H),0.64(t,J＝7.4Hz,6H)； 13 C NMR(100MHz,CDCl 3 )δ161.51,159.80,146.03,144.88,129.46,127.36,127.28,117.75,107.27,42.57,38.62,26.24,11.77.
example 16
Adding 50-80 mL of chlorobenzene into a 250mL single-neck flask, and then adding 10mmol of chlorobenzene
And 10mmol of
Reflux reaction at 100 deg.c for 12 hr, decompression eliminating solvent to obtain coarse product, and fast column chromatographic separation to obtain the product
35.7mg (66%). The structure of the product characterizes the physical constants:
1 H NMR(400MHz,CDCl 3 )δ7.41-7.35(m,2H),7.31(t,J＝7.2Hz,1H),7.21-7.17(m,2H),6.18(d,J＝3.4Hz,1H),5.84(d,J＝3.4Hz,1H),3.41(s,3H),2.92-2.82(m,1H),1.82-1.73(m,2H),1.60-1.47(m,4H),1.40-1.30(m,2H)； 13 C NMR(100MHz,CDCl 3 )δ162.55,159.68,145.73,144.78,129.48,127.41,127.36,117.84,105.39,38.61,38.57,31.61,25.32.
example 17
50 to E is added into a 250mL single-neck flask80mL of chlorobenzene, 10mmol of
And 10mmol of
Reflux reaction at 100 deg.c for 12 hr, decompression eliminating solvent to obtain coarse product, and fast column chromatographic separation to obtain the product
20.8mg (37%). The structure of the product characterizes the physical constants:
1 H NMR(400MHz,CDCl 3 )δ7.41-7.35(m,2H),7.31(t,J＝7.2Hz,1H),7.21-7.17(m,2H),6.17(d,J＝3.4Hz,1H),5.86(d,J＝3.4Hz,1H),5.68-5.57(m,2H),3.41(s,3H),2.75-2.66(m,1H),2.18-1.75(m,5H),1.46-.35(m,1H)； 13 C NMR(100MHz,CDCl 3 )δ162.45,159.68,145.79,144.76,129.52,127.47,127.40,126.92,125.48,117.76,105.30,38.57,33.32,29.42,26.92,24.65.
example 18
Adding 50-80 mL of chlorobenzene into a 250mL single-neck flask, and then adding 10mmol of chlorobenzene
And 10mmol of
Reflux reaction at 100 deg.c for 12 hr, decompression eliminating solvent to obtain coarse product, and fast column chromatographic separation to obtain the product
32.0mg (66%). The structure of the product characterizes the physical constants:
1 H NMR(400MHz,CDCl 3 )δ7.41-7.35(m,2H),7.34-7.28(m,1H),7.22-7.18(m,2H),6.18(d,J＝3.4Hz,1H),5.83(dd,J＝3.4,0.6Hz,1H),3.42(s,3H),2.75-2.67(m,1H),1.00(d,J＝7.0Hz,6H)； 13 C NMR(100MHz,CDCl 3 )δ164.09,159.68,145.72,144.76,129.47,127.45,127.35,117.76,104.69,38.54,27.90,20.71.
example 19
Adding 50-80 mL of chlorobenzene into a 250mL single-neck flask, and then adding 10mmol of sum
10mmol of
Reflux reaction at 100 deg.c for 12 hr, decompression eliminating solvent to obtain coarse product, and fast column chromatographic separation to obtain the product
32.3mg (54%). The structure of the product characterizes the physical constants: 1 H NMR(400MHz,CDCl 3 )δ7.41-7.34(m,2H),7.33-7.27(m,1H),7.21-7.16(m,2H),6.38(d,J＝3.4Hz,1H),5.85(d,J＝3.4Hz,1H),3.41(s,3H),2.37-2.29(m,1H),1.40-1.14(m,6H),1.00-0.95(m,2H),0.82(t,J＝7.4Hz,3H),0.63(t,J＝7.4Hz,3H)； 13 C NMR(100MHz,CDCl 3 )δ161.77,159.79,145.98,144.87,129.45,127.38,127.29,117.81,107.12,40.92,38.63,33.09,29.52,26.66,22.66,14.09,11.77.
example 20
Adding 50-80 mL of chlorobenzene into a 250mL single-neck flask, and then adding 10mmol of mixture
10mmol of
Reflux reaction at 100 deg.c for 12 hr, decompression eliminating solvent to obtain coarse product, and fast column chromatographic separation to obtain the product
14.1mg (29%). The structure of the product characterizes the physical constants:
1 H NMR(400MHz,CDCl 3 )δ7.42-7.30(m,3H),7.22-7.18(m,2H),5.94(d,J＝3.4Hz,1H),5.82(d,J＝3.4Hz,1H),3.42(s,3H),2.43(t,J＝7.4Hz,2H),1.49-1.39(m,2H),0.82(t,J＝7.4Hz,3H)； 13 C NMR(100MHz,CDCl 3 )δ159.71,158.97,145.68,144.69,129.56,127.63,127.52,117.79,106.87,38.55,30.05,20.94,13.71.
example 21
Adding 50-80 mL of chlorobenzene into a 250mL single-neck flask, and then adding 10mmol of sum
10mmol of
Reflux reaction at 100 deg.c for 12 hr, decompression eliminating solvent to obtain coarse product, and fast column chromatographic separation to obtain the product
15.4mg (30%). The structure of the product characterizes the physical constants: 1 H NMR(400MHz,CDCl 3 )δ7.41-7.30(m,3H),7.22-7.18(m,2H),6.01(d,J＝3.2Hz,1H),5.83(d,J＝3.2Hz,1H),3.41(s,3H),2.30(d,J＝7.2Hz,2H),1.75-1.66(m,1H),0.78(d,J＝6.6Hz,6H)； 13 C NMR(100MHz,CDCl 3 )δ159.72,158.24,145.84,144.72,129.54,127.56,127.48,117.78,107.71,38.57,37.23,27.59,22.36.
example 22
Adding 50-80 mL of chlorobenzene into a 250mL single-neck flask, and then adding 10mmol of sum
10mmol of
Reflux reaction at 100 deg.c for 12 hr, decompression eliminating solvent to obtain coarse product, and fast column chromatographic separation to obtain the product
14.9mg (29%). The structure of the product characterizes the physical constants:
1 H NMR(400MHz,CDCl 3 )δ7.42-7.30(m,3H),7.22-7.18(m,2H),5.96(d,J＝3.2Hz,1H),5.81(d,J＝3.2Hz,1H),3.41(s,3H),2.44(t,J＝7.6Hz,2H),1.43-1.34(m,2H),1.27-1.17(m,2H),0.85(t,J＝7.2Hz,3H)； 13 C NMR(100MHz,CDCl 3 )δ159.72,159.16,145.68,144.72,129.55,127.62,127.52,117.82,106.72,38.56,29.68,27.79,22.23,13.81.
in addition to the above embodiments, the organic solvent of the present invention may be at least one of benzene, toluene, xylene, mesitylene, chlorobenzene, o-dichlorobenzene, m-dichlorobenzene, p-dichlorobenzene, fluorobenzene, pentafluorobenzene, hexafluorobenzene, ethyl acetate, t-butyl acetate, propyl acetate, acetonitrile, benzonitrile, tetrahydrofuran, diethyl ether, 1, 4-dioxane.
The initiator can also be at least one of azodiisobutyronitrile, benzoyl peroxide, t-butyl peroxide, acetyl peroxide and di-t-butyl peroxide.
The catalyst may also be Fe (OAc) 2 、Cu(OAc) 2 、Co(OAc) 2 、Mn(OAc) 2、 Pd(OAc) 2、 Ni(acac) 2 、Fe(acac) 2 、Fe(OTf) 2 、FeCl 2 、Fe(acac) 3 、Fe(OTf) 3 、FeCl 3 、FeCl 2 At least one of (a).
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (8)
1. A method for preparing 2, 5-disubstituted furan compounds is characterized by comprising the following steps:
RCHO, RCHO,
Adding an initiator and a catalyst into an organic solvent, and performing reflux reaction to obtain
Wherein RCHO and
in a molar ratio of 100: 1-1: 100, respectively; the molar ratio of RCHO to initiator is 100: 1-1: 100, respectively; the molar ratio of RCHO to catalyst is 100: 1-1: 100;
wherein R is saturated aliphatic hydrocarbon or alicyclic hydrocarbon of C1-C12;
x is H OR OR 1 Wherein R is 1 Is hydrogen, saturated aliphatic hydrocarbon of C1-C6 or
R 2 Is hydrogen, an electron donating group or an electron withdrawing group;
or X is NR 3 R 4 Wherein R is 3 、R 4 Is hydrogen, saturated aliphatic hydrocarbon of C1-C6 or
R 5 Hydrogen, an electron donating group or an electron withdrawing group.
2. The method of claim 1, wherein the electron donating group is OH or CH 3 、OCH 3 、OC 2 H 5 、N(CH 3 ) 2 Or N (C) 2 H 5 ) 2 。
3. The method for preparing 2, 5-disubstituted furans according to claim 1 or 2, wherein the electron-withdrawing group is Cl, Br, F, NO 2 CN or CF 3 。
4. The method for preparing 2, 5-disubstituted furans according to claim 1, wherein the reaction temperature of the reflux reaction is 100 to 160 ℃ and the reaction time is 1 to 60 hours.
5. The method according to claim 1, wherein the organic solvent is at least one selected from the group consisting of benzene, toluene, xylene, mesitylene, chlorobenzene, o-dichlorobenzene, m-dichlorobenzene, p-dichlorobenzene, fluorobenzene, pentafluorobenzene, hexafluorobenzene, ethyl acetate, t-butyl acetate, propyl acetate, acetonitrile, benzonitrile, tetrahydrofuran, diethyl ether, and 1, 4-dioxane.
6. The method for preparing 2, 5-disubstituted furans according to claim 1, wherein the initiator is at least one of azodiisobutyronitrile, benzoyl peroxide, t-butyl peroxide, acetyl peroxide, di-t-butyl peroxide.
7. The method of claim 1, wherein the catalyst is Fe (OAc) 2 、Cu(OAc) 2 、Co(OAc) 2 、Mn(OAc) 2 、Pd(OAc) 2 、Ni(acac) 2 、Fe(acac) 2 、Fe(OTf) 2 、FeCl 2 、Fe(acac) 3 、Fe(OTf) 3 、FeCl 3 、FeCl 2 At least one of (1).
8. The method of claim 1, wherein the 2, 5-disubstituted furans have the following structure:
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| Cholinergic agents structurally related to furtrethonium. 1;S Manfredini et al.;《Eur. J. Med. Chem.》;19941231;第29卷;第153-161页 * |
| Iron-Catalyzed Oxidative Decarbonylative α‑Alkylation of Acyl-Substituted Furans with Aliphatic Aldehydes as the Alkylating Agents;Wenkun Luo et al.;《J. Org. Chem.》;20200611;第85卷;第9396-9404页 * |
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