CN113735804B - Synthesis method of butenolide compound - Google Patents
Synthesis method of butenolide compound Download PDFInfo
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- CN113735804B CN113735804B CN202111172680.1A CN202111172680A CN113735804B CN 113735804 B CN113735804 B CN 113735804B CN 202111172680 A CN202111172680 A CN 202111172680A CN 113735804 B CN113735804 B CN 113735804B
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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
- C07D307/58—One oxygen atom, e.g. butenolide
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Abstract
The invention discloses a synthesis method of butenolide compounds, which comprises the following steps: acrylic compound, paraformaldehyde, pentamethyl cyclopentadienyl cobalt carbonyl diiodoxide and AgSbF 6 Adding sodium acetate into organic solvent, heating under air condition to reactAnd after the completion, the butenolide compound is obtained after post-treatment. The method synthesizes the butene lactone compound by a simple and easily obtained raw material one-pot method, has high conversion efficiency and good step economy; meanwhile, the synthesis 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 synthesis method of butenolide compounds.
Background
Butenolide compounds are a very important and common framework, widely existing in bioactive molecules and drug molecules, are important substrates for screening the activity of the drug molecules, and are also important intermediates for pharmaceutical chemistry and organic synthesis. Chemists have developed a number of methods to build this important backbone, traditional methods such as the Pauson-Khand reaction, which typically require pre-functionalization of the substrate, are tedious, have poor reaction selectivity, and are harsh. Therefore, it is highly desirable to develop novel and efficient methods for constructing butenolide skeletons.
The strategy of transition metal catalyzed guide group assisted C-H bond activation has been developed for decades as a powerful tool in organic synthesis, and an atomic economical and step economical method is provided for efficiently synthesizing complex molecules. However, considering that palladium, rhodium, iridium and other catalysts are expensive, much attention has recently been paid to catalyzing the c—h activation reaction using a relatively inexpensive transition metal, wherein cobalt catalysts exhibit excellent catalytic activity. Compared with rhodium catalyst, the catalyst has the advantages of lower electronegativity, stronger Lewis acidity, low cost, low toxicity and the like, and recently Cp is Co (CO) I 2 The catalyzed directed C-H activation reaction gradually becomes a hot spot. However, most of these reactions are limited to C-H activation of aromatic hydrocarbons, and the directing groups typically require pre-installation, adding synthetic steps, limiting the application of the method to synthesis. Carboxyl groups are common functional groups that are widely present in organic molecules, whereas carboxylic acids are readily available starting materials in organic synthesis. Based on the fact that carboxylic acids are inexpensive and readily available and can act as traceless directing groups, a great deal of attention has been focused on carboxylic acid directed C-H activation reactions. Although there has been great progress in this field, the use of acrylic acid-directed C-H activation of olefins to build complex molecules has not been fully developed. Against this background, we have developed a one-pot synthesis of butenolide using an acrylic compound catalyzed by inexpensive metallic cobalt and paraformaldehyde. The method is simple and convenient to operate, has low-cost and easily-obtained substrate, wide universality and good functional group compatibility, and provides a simple and efficient method for synthesizing the butenolide derivatives with diversified structures.
Disclosure of Invention
The invention provides a synthesis method of butenolide compounds, which has wide substrate universality and high reaction yield.
A synthetic method of butenolide compounds comprises the following steps: adding an acrylic compound, paraformaldehyde, pentamethyl cyclopentadienyl carbonyl diiodocobaltous 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 a formula (II):
the structure of the butenolide compound is shown as a formula (I):
in the formulas (I) - (II), R is selected from aryl;
preferably, the butenolide compound is one of compounds shown in the formula (I-1) -formula (I-12):
preferably, the organic solvent is Hexafluoroisopropanol (HFIP).
Preferably, all additives are AgSbF 6 The 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 100-110℃and the reaction time is 6 hours.
Preferably, the base of the reaction is sodium acetate.
Compared with the prior art, the invention has the beneficial effects that:
(1) The method synthesizes the butenolide compound with high yield by a very simple and easily obtained raw material one-pot method, and has high conversion efficiency and good step economy;
(2) The synthesis method of the invention has simple operation, high reaction yield and good substrate universality and functional group compatibility.
Drawings
FIG. 1 is a graph showing the hydrogen spectrum and the carbon spectrum of the compound obtained in example 1;
FIG. 2 is a graph showing the hydrogen spectrum and the carbon spectrum of the compound obtained in example 2;
FIG. 3 is a graph showing the hydrogen spectrum and the carbon spectrum of the compound obtained in example 3;
FIG. 4 is a graph showing the hydrogen spectrum and the carbon spectrum of the compound obtained in example 4;
FIG. 5 is a graph showing the hydrogen spectrum and the carbon spectrum of the compound obtained in example 5;
FIG. 6 is a graph showing the hydrogen spectrum and the carbon spectrum of the compound obtained in example 6;
FIG. 7 is a graph showing the hydrogen spectrum and the carbon spectrum of the compound obtained in example 7;
FIG. 8 is a graph showing the hydrogen spectrum and the carbon spectrum of the compound obtained in example 8;
FIG. 9 is a graph showing the hydrogen spectrum and the carbon spectrum of the compound obtained in example 9;
FIG. 10 is a graph showing the hydrogen spectrum and the carbon spectrum of the compound obtained in example 10;
FIG. 11 is a graph showing the hydrogen spectrum and the carbon spectrum of the compound obtained in example 11;
FIG. 12 is a graph showing the hydrogen spectrum and the carbon spectrum of the compound obtained in example 12;
wherein the hydrogen spectrum was tested on a 400MHz nuclear magnetic instrument. The carbon spectrum was tested on a 100MHz nuclear magnetic instrument. The test conditions were all room temperature using tetramethylsilane as an internal standard and the samples were dissolved in deuterated chloroform.
Detailed Description
The invention is further described with reference to the following specific examples, which are all the best modes for carrying out the invention.
Examples 1 to 12
Acrylic compound (0.2 mmol), paraformaldehyde (0.6 mmol), pentamethyl cyclopentadienyl carbonyl diiodo cobalt (0.010 mmol), sodium acetate (0.3 mmol) and AgSbF were added to a test tube according to the raw material ratios of Table 1 6 (0.04 mmol) and 2.0ml of organic solvent, and after the reaction is completed according to the reaction conditions of the table 2, cooling, suction filtering, mixing the sample with silica gel, purifying by column chromatography to obtain the corresponding 1-indenone 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 for examples 1-12
In tables 1 and 2, T is the reaction temperature, T is the reaction time, 1-workbench is 1-substituted naphthyl, and 2-workbench is 2-substituted naphthyl.
Examples 1 to 12 give structure confirmation data for some compounds:
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℃. 1 H 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)； 13 C 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℃. 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(100MHz,CDCl 3 )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(petroleumether:EtOAc＝6:1)to afford a white solid(35.4mg,93％),mp 119-120℃. 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(100MHz,CDCl 3 )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℃.. 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(100MHz,CDCl 3 )δ172.2,163.3(d,J C-F ＝248.2Hz),143.9,130.6,128.9(d,J C-F ＝8.2Hz),125.7(d,J C-F ＝3.4Hz),115.7(d,J C-F ＝21.6Hz),69.5. 19 F NMR(300MHz,CDCl 3 )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℃. 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(100MHz,CDCl 3 )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℃. 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(100MHz,CDCl 3 )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℃. 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(100MHz,CDCl 3 )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℃. 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(100MHz,CDCl 3 )δ171.8,146.4,133.0,131.3(q,J C-CF3 ＝32.5Hz),127.4,125.8(q,J C-CF3 ＝3.8Hz),124.0(q,J C-CF3 ＝270.6Hz),69.8. 19 F NMR(300MHz,CDCl 3 )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％). 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(100MHz,CDCl 3 )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℃. 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(100MHz,CDCl 3 )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％). 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(100MHz,CDCl 3 )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℃. 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(100MHz,CDCl 3 )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. the synthesis method of the butenolide compound is characterized by comprising the following steps of: adding an acrylic compound, paraformaldehyde, pentamethyl cyclopentadienyl carbonyl diiodocobaltate, an additive and alkali 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 structure of the acrylic compound is shown as a formula (II):
the structure of the butenolide compound is shown as a formula (I):
in the formulas (I) to (II), R is selected from substituted or unsubstituted aryl;
the substituents on the aryl groups are selected from C 1 ～C 4 Alkyl, C 1 ～C 4 Alkoxy, halogen or trifluoromethyl.
2. The method for synthesizing butenolide according to claim 1, wherein the aryl group is naphthyl, substituted or unsubstituted phenyl;
the substituent on the phenyl is methyl, methoxy, F, cl, br, I or trifluoromethyl.
3. The method for synthesizing butenolide compound according to claim 1, wherein the butenolide compound is one of compounds represented by formulas (I-1) - (I-12):
4. the method for synthesizing butenolide according to claim 1, wherein the organic solvent is Hexafluoroisopropanol (HFIP).
5. The method for synthesizing butenolide compound according to claim 1, wherein all the alkali is sodium acetate, the reaction temperature is 100-110 ℃, and the reaction time is 6-10 hours under an air atmosphere.
6. The method for synthesizing butenolide according to claim 1, wherein all additives are AgSbF 6 。
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