CN113735804A - Method for synthesizing butenolide compounds - Google Patents
Method for synthesizing butenolide compounds Download PDFInfo
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- CN113735804A CN113735804A CN202111172680.1A CN202111172680A CN113735804A CN 113735804 A CN113735804 A CN 113735804A CN 202111172680 A CN202111172680 A CN 202111172680A CN 113735804 A CN113735804 A CN 113735804A
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- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- 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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Abstract
The invention discloses a method for synthesizing butenolide compounds, which comprises the following steps: mixing acrylic acid compound, paraformaldehyde, pentamethylcyclopentadienyl carbonyl diiodo cobalt and AgSbF6And adding sodium acetate into an organic solvent, heating under the air condition for reaction, and after the reaction is completed, carrying out post-treatment to obtain the butenolide compound. The method synthesizes the butenolide compound by a simple and easily-obtained raw material one-pot method, and has high conversion efficiency and good economical efficiency of steps; meanwhile, the synthetic method is simple to operate, high in reaction yield and wide in substrate universality.
Description
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a method for synthesizing butenolide compounds.
Background
The butenolide compounds are very important and common frameworks, widely exist in bioactive molecules and drug molecules, are important substrates for activity screening of drug molecules, and are also important intermediates for pharmaceutical chemistry and organic synthesis. Chemists have developed many methods to build this important framework, and conventional methods such as the Pauson-Khand reaction typically require pre-functionalization of the substrate, lengthy reaction steps, poor reaction selectivity, and harsh reaction conditions. Therefore, it is necessary to develop a novel and efficient method for constructing the butenolide skeleton compounds.
Strategy for transition metal catalyzed C-H bond activation assisted by a directing group over decadesHas become a powerful tool in organic synthesis, and provides an atom-economic and step-economic method for efficiently synthesizing complex molecules. However, in consideration of the high price of palladium, rhodium, iridium and other catalysts, much attention has been paid to the catalysis of C-H activation reaction by using relatively cheap transition metals, wherein cobalt catalysts show good catalytic activity. Compared with rhodium catalyst, it has the advantages of lower electronegativity, stronger Lewis acidity, low cost, low toxicity, etc., and recently Cp Co (CO) I2The catalyzed, directed C — H activation reaction gradually becomes a hot spot. However, these reactions are mostly limited to C-H activation of aromatic hydrocarbons, and the directing group usually needs to be pre-installed, adding a synthetic step and limiting the application of the method in synthesis. Carboxyl groups are common functional groups widely present in organic molecules, while carboxylic acids are readily available starting materials in organic synthesis. Based on the availability of carboxylic acids that are inexpensive and can act as traceless directing groups, much attention has been focused on carboxylic acid-directed C-H activation reactions. Despite the tremendous advances made in this area, the application of C-H activation of acrylic acid-directed olefins to build complex molecules has not been fully developed. Based on the background, a subject group develops a one-pot method for synthesizing butenolide compounds by using acrylic compounds and paraformaldehyde which are catalyzed by cheap metal cobalt. The method is simple and convenient to operate, the substrate is cheap and easy to obtain, the universality is wide, the functional group compatibility is good, and a simple and efficient method is provided for synthesizing the butenolide derivatives with diversified structures.
Disclosure of Invention
The invention provides a method for synthesizing butenolide compounds, which has the advantages of wide substrate universality and high reaction yield.
A method for synthesizing butenolide compounds comprises the following steps: adding an acrylic compound, paraformaldehyde, pentamethylcyclopentadienyl carbonyl diiodocobalt and sodium acetate into an organic solvent, heating under the air condition for reaction, and after the reaction is completed, carrying out post-treatment to obtain the 1-butenolide compound;
the structure of the acrylic compound is shown as the formula (II):
the structure of the paraformaldehyde is shown as a formula (III):
HCHO (III)
the structure of the butenolide compound is shown as the formula (I):
in the formulae (I) to (II), R1Is selected from aryl;
preferably, the butenolide compound is one of compounds shown in formula (I-1) to formula (I-12):
preferably, the organic solvent is Hexafluoroisopropanol (HFIP).
Preferably, all additives are AgSbF6The reaction temperature is 100-110 ℃, and the reaction time is 6 hours under the air atmosphere.
Preferably, the organic solvent is Hexafluoroisopropanol (HFIP).
Preferably, the reaction temperature is 100-.
Preferably, the base of the reaction is sodium acetate.
Compared with the prior art, the invention has the beneficial effects that:
(1) the method has the advantages that the butenolide compound is synthesized in a high yield by a very simple and easily-obtained raw material one-pot method, the conversion efficiency is high, and the economical efficiency of the steps is good;
(2) the synthetic method provided by the invention is simple to operate, high in reaction yield, and good in substrate universality and functional group compatibility.
Drawings
FIG. 1 is a hydrogen spectrum and a carbon spectrum of the compound obtained in example 1;
FIG. 2 is a hydrogen spectrum and a carbon spectrum of the compound obtained in example 2;
FIG. 3 shows a hydrogen spectrum and a carbon spectrum of the compound obtained in example 3;
FIG. 4 shows a hydrogen spectrum and a carbon spectrum of the compound obtained in example 4;
FIG. 5 shows a hydrogen spectrum and a carbon spectrum of the compound obtained in example 5;
FIG. 6 shows a hydrogen spectrum and a carbon spectrum of the compound obtained in example 6;
FIG. 7 shows a hydrogen spectrum and a carbon spectrum of the compound obtained in example 7;
FIG. 8 is a hydrogen spectrum and a carbon spectrum of the compound obtained in example 8;
FIG. 9 shows a hydrogen spectrum and a carbon spectrum of the compound obtained in example 9;
FIG. 10 is a hydrogen spectrum and a carbon spectrum of the compound obtained in example 10;
FIG. 11 is a hydrogen spectrum and a carbon spectrum of the compound obtained in example 11;
FIG. 12 shows a hydrogen spectrum and a carbon spectrum of the compound obtained in example 12;
wherein the hydrogen spectra were tested on a 400MHz nuclear magnetic instrument. Carbon spectra were tested on a 100MHz nuclear magnetic instrument. The test conditions were all determined at room temperature using tetramethylsilane as internal standard and the sample was dissolved in deuterated chloroform.
Detailed Description
The present invention will be further described with reference to specific examples, which are intended to be preferred embodiments of the invention.
Examples 1 to 12
Acrylic acid compound (0.2mmol), paraformaldehyde (0.6mmol), pentamethylcyclopentadienylcarbonyldiiodocobalt (0.010mmol), sodium acetate (0.3mmol), AgSbF were added to a test tube according to the raw material ratio in Table 16(004mmol) and 2.0ml of organic solvent, cooling, suction filtering, mixing with silica gel, and purifying by column chromatography to obtain the corresponding 1-indanone compound (I), wherein the reaction process is shown as the following formula:
TABLE 1 raw material ratios of examples 1 to 12
TABLE 2 reaction conditions and reaction results of examples 1 to 12
In tables 1 and 2, T is the reaction temperature, T is the reaction time, 1-naphthyl is a 1-substituted naphthyl group, and 2-naphthyl is a 2-substituted naphthyl group.
Structure confirmation data of partial compounds obtained by preparation of examples 1 to 12:
3-Phenylfuran-2(5H)-one(I-1):Purified by flash chromatography(petroleum ether:EtOAc＝6:1)to afford a pale yellow solid(29.5mg,92％),mp 88-89℃.1H NMR(400MHz,CDCl3)δ7.85-7.82(m,2H),7.64(t,J＝2.0Hz,1H),7.44-7.46(m,3H),4.91(d,J＝1.6Hz,2H)；13C NMR(100MHz,CDCl3)δ172.3,144.5,131.6,129.5,129.4,128.7,127.0,69.6.
3-(P-tolyl)furan-2(5H)-one(I-2):Purified by flash chromatography(petroleum ether:EtOAc＝6:1)to afford a white solid(31.4mg,90％),mp 102-104℃.1H NMR(400MHz,CDCl3)δ7.75(d,J＝8.4Hz,2H),7.59(t,J＝2.0Hz,1H),7.22(d,J＝7.6Hz,2H),4.91(d,J＝2.0Hz,2H),2.38(s,3H)；13C NMR(100MHz,CDCl3)δ172.4,143.3,139.5,131.5,129.4,126.8,126.7,69.5,21.4.
3-(4-Methoxyphenyl)furan-2(5H)-one(I-3):Purified by flash chromatography(petroleum ether:EtOAc＝6:1)to afford a white solid(35.4mg,93％),mp 119-120℃.1H NMR(400MHz,CDCl3)δ7.84-7.80(m,2H),7.52(t,J＝2.0Hz,1H),6.95-6.92(m,2H),4.90(d,J＝2.0Hz,2H),3.83(s,3H)；13C NMR(100MHz,CDCl3)δ172.6,160.4,142.0,131.0,128.4,122.1,114.1,69.5,55.4.
3-(4-Fluorophenyl)furan-2(5H)-one(I-4):Purified by flash chromatography(petroleum ether:EtOAc＝6:1)to afford a white solid(30.3mg,85％),mp 77-78℃..1H NMR(400MHz,CDCl3)δ7.88-7.83(m,2H),7.61(t,J＝2.0Hz,1H),7.13-7.07(m,2H),4.92(d,J＝1.6Hz,2H)；13C NMR(100MHz,CDCl3)δ172.2,163.3(d,JC-F＝248.2Hz),143.9,130.6,128.9(d,JC-F＝8.2Hz),125.7(d,JC-F＝3.4Hz),115.7(d,JC-F＝21.6Hz),69.5.19F NMR(300MHz,CDCl3)δ-111.2.
3-(4-Chlorophenyl)furan-2(5H)-one(I-5):Purified by flash chromatography(petroleum ether:EtOAc＝5:1)to afford a a white solid(34.2mg,88％),mp 90-91℃.1H NMR(400MHz,CDCl3)δ7.82-7.79(m,2H),7.66(t,J＝2.0Hz,1H),7.40-7.37(m,2H),4.93(d,J＝1.6Hz,2H)；13C NMR(100MHz,CDCl3)δ172.0,144.5,135.4,130.6,128.9,128.3,127.9,69.6.
3-(4-Bromophenyl)furan-2(5H)-one(I-6):Purified by flash chromatography(petroleum ether:EtOAc＝5:1)to afford a white solid(37.3mg,78％),mp 105-106℃.1H NMR(400MHz,CDCl3)δ7.75-7.72(m,2H),7.67(t,J＝2.0Hz,1H),7.55-7.52(m,2H),4.92(d,J＝2.0Hz,2H)；13C NMR(100MHz,CDCl3)δ171.9,144.7,131.9,130.7,128.5,128.4,123.7,69.6.
3-(4-Iodophenyl)furan-2(5H)-one(I-7):Purified by flash chromatography(petroleum ether:EtOAc＝5:1)to afford a white solid(41.2mg,72％),mp 131-132℃.1H NMR(400MHz,CDCl3)δ7.74(d,J＝8.4Hz,2H),7.68(t,J＝1.6Hz,1H),7.59(d,J＝8.4Hz,2H),4.91(d,J＝1.6Hz,2H)；13C NMR(100MHz,CDCl3)δ171.9,144.7,137.9,130.8,128.9,128.6,95.6,69.6.
3-(4-(Trifluoromethyl)phenyl)furan-2(5H)-one(I-8):Purified by flash chromatography(petroleum ether:EtOAc＝5:1)to afford a white solid(31.9mg,70％),mp 74-75℃.1H NMR(400MHz,CDCl3)δ7.98(d,J＝8.0Hz,2H),7.78(t,J＝2.0Hz,1H),7.67(d,J＝8.4Hz,2H),4.98(d,J＝1.6Hz,2H)；13C NMR(100MHz,CDCl3)δ171.8,146.4,133.0,131.3(q,JC-CF3＝32.5Hz),127.4,125.8(q,JC-CF3＝3.8Hz),124.0(q,JC-CF3＝270.6Hz),69.8.19F NMR(300MHz,CDCl3)δ-62.8.
3-(3-Methoxyphenyl)furan-2(5H)-one(I-9):Purified by flash chromatography(petroleum ether:EtOAc＝5:1)to afford a yellow oil(27.8mg,73％).1H NMR(400MHz,CDCl3)δ7.64(t,J＝2.0Hz,1H),7.44(t,J＝2.0Hz,1H),7.42-7.40(m,1H),7.32(t,J＝8.0Hz,1H),6.95-6.92(m,1H),4.92(d,J＝1.6Hz,2H),3.84(s,3H)；13C NMR(100MHz,CDCl3)δ172.1,159.7,144.6,131.5,130.8,129.7,119.4,115.1,112.4,69.5,55.4.
3-(2-Methoxyphenyl)furan-2(5H)-one(I-10):Purified by flash chromatography(petroleum ether:EtOAc＝5:1)to afford a white solid(25.1mg,66％),mp 84-85℃.1H NMR(400MHz,CDCl3)δ8.14(dd,J＝1.6,8.0Hz,1H),7.98(t,J＝2.0Hz,1H),7.37-7.32(m,1H),7.05-7.01(m,1H),6.96(d,J＝8.4Hz,1H),4.92(d,J＝2.0Hz,2H),3.88(s,3H)；13C NMR(100MHz,CDCl3)δ173.2,157.6,148.4,130.2,129.4,126.7,120.6,118.5,110.8,69.8,55.4.
3-(Naphthalen-1-yl)furan-2(5H)-one(I-11):Purified by flash chromatography(petroleum ether:EtOAc＝5:1)to afford a colorless oil(26.1mg,62％).1H NMR(400MHz,CDCl3)δ7.92-7.88(m,3H),7.65(t,J＝2.0Hz,1H),7.59-7.57(m,1H),7.54-7.50(m,3H),5.07(d,J＝2.0Hz,2H)；13C NMR(100MHz,CDCl3)δ173.0,149.0,133.7,132.3,131.1,129.6,128.7,127.5,127.4,126.7,126.2,125.2,124.6,70.3.
3-(Naphthalen-2-yl)furan-2(5H)-one(I-12):Purified by flash chromatography(petroleum ether:EtOAc＝5:1)to afford a white solid(34.5mg,82％),mp 145-147℃.1H NMR(400MHz,CDCl3)δ8.59(s,1H),7.93-7.82(m,3H),7.79-7.74(m,2H),7.54-7.49(m,2H),4.96(d,J＝2.0Hz,2H)；13C NMR(100MHz,CDCl3)δ172.4,144.4,133.5,133.2,131.3,128.9,128.41,127.6,127.0,126.7,126.7,126.6,124.1,69.6。
Claims (6)
1. a method for synthesizing butenolide compounds is characterized by comprising the following steps: adding an acrylic compound, paraformaldehyde, pentamethylcyclopentadienyl carbonyl diiodo cobalt, an additive and alkali into an organic solvent, heating under the air condition for reaction, and carrying out post-treatment after the reaction is completed to obtain the butenolide compound;
the structure of the acrylic compound is shown as the formula (II):
the structure of the paraformaldehyde is shown as a formula (III):
HCHO (III)
the structure of the butenolide compound is shown as the formula (I):
in the formulae (I) to (II), R1Selected from substituted or unsubstituted aryl;
the substituents on the aryl are selected from C1～C4Alkyl radical, C1～C4Alkoxy radical,Halogen or trifluoromethyl.
2. The method for synthesizing butenolide compounds according to claim 1, wherein the aryl group is naphthyl, substituted or unsubstituted phenyl;
and the substituent on the phenyl is methyl, methoxy, F, Cl, Br, I or trifluoromethyl.
3. The method for synthesizing butenolide compounds according to claim 1, wherein the butenolide compounds are one of compounds represented by the following formulae (I-1) to (I-12):
4. the method for synthesizing butenolide compounds according to claim 1, wherein the organic solvent is Hexafluoroisopropanol (HFIP).
5. The method for synthesizing butenolide compounds as claimed in claim 1, wherein the alkali is sodium acetate, the reaction temperature is 100 ℃ and 110 ℃, and the reaction time is 6-10 hours in the air atmosphere.
6. The method for synthesizing butenolide compounds according to claim 1, wherein all the additives are AgSbF6。
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998041511A1 (en) * | 1997-03-14 | 1998-09-24 | Merck Frosst Canada & Co. | Pyridazinones as inhibitors of cyclooxygenase-2 |
| KR101140134B1 (en) * | 2009-12-30 | 2012-05-02 | 강원대학교산학협력단 | Novel 3-arylbutenolide derivatives and its preparation method |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998041511A1 (en) * | 1997-03-14 | 1998-09-24 | Merck Frosst Canada & Co. | Pyridazinones as inhibitors of cyclooxygenase-2 |
| KR101140134B1 (en) * | 2009-12-30 | 2012-05-02 | 강원대학교산학협력단 | Novel 3-arylbutenolide derivatives and its preparation method |
Non-Patent Citations (3)
| Title |
|---|
| JEREMY FOURNIER等: "Palladium-Catalyzed Asymmetric Allylic Alkylation of Cyclic Dienol Carbonates: Efficient Route to Enantioenriched g-Butenolides Bearing an All-Carbon a-Quaternary Stereogenic Center", 《ANGEWANDTE CHEMIE, INTERNATIONAL EDITION》 * |
| SEAN S. NGUYEN等: "Butenolide synthesis from functionalized cyclopropenones", 《AMERICAN CHEMICAL SOCIETY》 * |
| WESLEY J. OLIVIER等: "Revised Structures of Dehydrostenines A and B: TotalSyntheses of (±)-Dehydrostenine A and Structure Assigned to Dehydrostenine B", 《CHEMISTRY—A EUROPEAN JOURNAL》 * |
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