CN108276233B - Method for synthesizing amide compound - Google Patents
Method for synthesizing amide compound Download PDFInfo
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- CN108276233B CN108276233B CN201710009402.1A CN201710009402A CN108276233B CN 108276233 B CN108276233 B CN 108276233B CN 201710009402 A CN201710009402 A CN 201710009402A CN 108276233 B CN108276233 B CN 108276233B
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- C07B43/06—Formation or introduction of functional groups containing nitrogen of amide groups
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- C07C231/00—Preparation of carboxylic acid amides
- C07C231/06—Preparation of carboxylic acid amides from nitriles by transformation of cyano groups into carboxamide groups
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Abstract
The invention discloses a method for synthesizing a compound shown as a formula I, which comprises the following steps: reacting a compound II, a compound III and a compound IV by a catalyst to generate a compound shown in a formula I, wherein the compound II is selected from one of the compounds shown in the formula II, the compound III is selected from at least one of the compounds shown in the formula III-1 and the formula III-2, the compound IV is selected from one of the compounds shown in the formula IV,
R4CN is of formula IV wherein R3And R4Independently selected from one of hydrocarbyl, substituted hydrocarbyl, heteroaryl and substituted heteroaryl.
Description
Technical Field
The invention relates to a method for synthesizing amide compounds.
Background
α -alkyl substituted amines exhibit excellent biological activities such as antibacterial, weight-reducing, anti-inflammatory, antiviral, anticancer, etc. therefore, it is crucial and urgent to develop a rapid synthesis method for α -alkyl substituted amines.
The carboamination reaction of olefins is an efficient synthetic strategy to build the most prevalent C-C and C-N bonds in nature. I.e., direct conversion of simple olefins to a wide variety of amines, has received considerable attention. It is now known that Cu, Rh and Ru have been reported as successful cases for catalyzing the amino-arylation, amino-trifluoromethylation, amino-cyanation and amino-carbonylation reactions of olefins. However, due to the lack of efficient reaction pathways and alkyl electrophiles, amino-alkylation of olefins has not always achieved a breakthrough and remains a major gap in the field of amino-carbonation of olefins.
The radical species formed in the decarboxylative coupling reaction of a common alkyl carboxylic acid without a heteroatom at the α -position is unstable compared to aryl carboxylic acids, so that alkyl carboxylic acids still present great challenges as alkyl electrophiles.
Disclosure of Invention
According to one aspect of the invention, a method for synthesizing an amide compound shown as a formula I is provided, and the method comprises the following steps: reacting the compound II, the compound III and the compound IV in a reaction system containing a catalyst to generate an amide compound shown as a formula I,
wherein the compound II is selected from one of the compounds shown in the formula II, the compound III is selected from at least one of the compounds shown in the formula III-1 and the formula III-2, the compound IV is selected from one of the compounds shown in the formula IV,
R4CN is shown in the formula IV of the formula,
wherein the content of the first and second substances,
R3and R4Independently selected from one of hydrocarbyl, substituted hydrocarbyl, heteroaryl and substituted heteroaryl.
In a preferred embodiment, said R is3And R4Independently selected from C1To C20A hydrocarbon group of1To C20Substituted hydrocarbyl of (2), C3To C20Heteroaryl of (e.g. C)6To C20Heteroaryl of) and C3To C20Substituted heteroaryl of (e.g. C)6To C20Substituted heteroaryl) of (a). C1To C20The hydrocarbon group of (A) may further be C3To C20Aryl (e.g. C)6To C20Aryl groups of (a); c1To C20The substituted hydrocarbon group of (A) may further be C3To C20Substituted aryl of (e.g. C)6To C20Substituted aryl group of (a).
The compound II shown in formula II may be a compound having a cyclic structure, or a compound having a chain structure, and the position of the carbon-carbon double bond may be in the chain structure or the cyclic structure. The "+" position in formula II is linked to other groups or atoms, which may be carbon atoms, for example.
In addition, it is to be noted that the person skilled in the art, according to the chemical reaction of the invention, is assured of R as above3When the group is only, the mixture of the compounds shown as the formula III-1 and the formula III-2 can be used as the reaction raw material of the invention. That is, in one embodiment, the compound III of the present invention is selected from one of the compounds represented by the formula III-1 and/or one of the compounds represented by the formula III-2, and when the compound III is composed of one of the compounds represented by the formula III-1 and one of the compounds represented by the formula III-2, R in the compound represented by the formula III-13A radical and a compound of formula III-2R of the compound shown3The groups are the same.
In one embodiment, the compound II is one of the compounds shown in the formula II-1,
R21、R22、R23and R24Independently selected from one of H, hydrocarbyl, substituted hydrocarbyl, heteroaryl, substituted heteroaryl, and non-hydrocarbyl substituents.
Preferably, said R is21、R22、R23And R24Independently selected from C1To C20A hydrocarbon group of1To C20Substituted hydrocarbyl of (2), C3To C20Heteroaryl of (e.g. C)6To C20Heteroaryl of (a), C3To C20Substituted heteroaryl of (e.g. C)6To C20Substituted heteroaryl) and non-hydrocarbon substituents. C1To C20The hydrocarbon group of (A) may further be C3To C20Aryl (e.g. C)6To C20Aryl groups of (a); c1To C20The substituted hydrocarbon group of (A) may further be C3To C20Substituted aryl of (e.g. C)6To C20Substituted aryl group of (a).
Preferably, the compound II is one of compounds shown as a formula II-2, a formula II-3, a formula II-4, a formula II-5, a formula II-6 and a formula II-7;
wherein m1 and m2 are independently selected from integers of 0 to 5;
m3 is selected from an integer from 0 to 7;
m4 is selected from an integer from 0 to 14;
R21、R22、R23and R24Independently selected from one of H, hydrocarbyl, substituted hydrocarbyl, heteroaryl, substituted heteroaryl, and non-hydrocarbyl substituents;
R5and R8Independently selected from one of hydrocarbyl, substituted hydrocarbyl, heteroaryl, substituted heteroaryl, and non-hydrocarbyl substituents;
R6and R7Independently selected from one of hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroaryl, substituted heteroaryl, and non-hydrocarbyl substituents.
Preferably, said R is21、R22、R23、R24、R5、R6、R7And R8Independently selected from C1To C20A hydrocarbon group of1To C20Substituted hydrocarbyl of (2), C3To C20Heteroaryl of (e.g. C)6To C20Heteroaryl of (a), C3To C20Substituted heteroaryl of (e.g. C)6To C20Substituted heteroaryl) and non-hydrocarbon substituents. C1To C20The hydrocarbon group of (A) may further be C3To C20Aryl (e.g. C)6To C20Aryl groups of (a); c1To C20The substituted hydrocarbon group of (A) may further be C3To C20Substituted aryl of (e.g. C)6To C20Substituted aryl group of (a).
When the compound II is shown as a formula II-1, the compound shown as the formula I is further shown as a formula I-1,
When the compound II is shown as a formula II-2, the compound shown as the formula I is further shown as a formula I-2,
When the compound II is shown as a formula II-3, the compound shown as the formula I is further shown as a formula I-3,
When the compound II is shown as a formula II-4, the compound shown as the formula I is further shown as a formula I-4,
When the compound II is shown as a formula II-5, the compound shown as the formula I is further shown as a formula I-5,
When the compound II is shown as a formula II-6, the compound shown as the formula I is further shown as a formula I-6,
When the compound II is shown as a formula II-7, the compound shown as the formula I is further shown as a formula I-7,
In one embodiment, the substituents in the substituted hydrocarbyl, substituted heteroaryl groups are non-hydrocarbon substituents; wherein the non-hydrocarbon substituent is at least one selected from the group consisting of oxygen, halogen, a group having a structural formula shown in formula (1), a group having a structural formula shown in formula (2), a group having a structural formula shown in formula (3), and a group having a structural formula shown in formula (4):
in the formula (1), M11Selected from hydrogen, C1To C10An alkyl group of (a);
in the formula (2), M21Selected from hydrogen, C1To C10An alkyl group of (a);
M31-O-formula (3)
In formula (3), M31Selected from hydrogen, C1To C10An alkyl group of (1).
In one embodiment, the substituents in the substituted hydrocarbyl group are selected from one of the halogens.
In one embodiment, the catalyst is selected from at least one of iron salts.
Fe3+And Fe2+All can be used in the embodiment of the present invention, and those skilled in the art can select suitable iron salt as the catalyst according to the needs. Thus, in a specific embodiment, the iron salt is selected from at least one of ferric chloride, ferrous chloride, ferric bromide, ferrous acetate, ferrous sulfate, ferrous nitrate, ferrous fluoride, ferric p-toluenesulfonate, ferrous trifluoromethanesulfonate and ferric trifluoromethanesulfonate.
In one embodiment, the compound having the formula shown in formula III-1 is prepared from a starting material comprising a compound having the formula shown in formula III-0 and hydrogen peroxide:
wherein R is3Is defined as above with R3Consistently, at least one selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, heteroaryl, and substituted heteroaryl. Preferably, it is selected from C1To C20A hydrocarbon group of1To C20Substituted hydrocarbyl of (2), C3To C20Heteroaryl and C3To C20At least one of substituted heteroaryl groups of (a).
In one embodiment, the compound having the formula shown in formula III-2 can be prepared from a starting material comprising a compound having the formula shown in formula III-0 and t-butyl hydroperoxide:
wherein R is3Is defined as above with R3Consistently, at least one selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, heteroaryl, and substituted heteroaryl. Preferably, it is selected from C1To C20A hydrocarbon group of1To C20Substituted hydrocarbyl of (2), C3To C20Heteroaryl and C3To C20At least one of substituted heteroaryl groups of (a).
In one embodiment, the compound having the formula shown in formula III-1 can be prepared from a feedstock containing the compound having the formula shown in formula III-0 and hydrogen peroxide and DCC and DMAP.
In one embodiment, the compound having the formula represented by formula III-2 can also be prepared from a starting material other than the two starting materials comprising the compound having the formula represented by formula III-0 and t-butyl hydroperoxide.
In one embodiment, the molar ratio of the compound II, the compound III, the compound IV to the catalyst is as follows:
compound II: compound III: compound IV: catalyst ═ (1-2): 1: (40-90): (0.01-0.2).
Preferably, the molar ratio of the compound II, the compound III, the compound IV to the catalyst is as follows:
compound II: compound III: compound IV: catalyst 1.5: (0.7-1.2): 77: 0.1.
in one embodiment, the temperature of the reaction is from 25 ℃ to 90 ℃ and the reaction time is from 1h to 7 h; preferably, the reaction temperature is 60 ℃ to 80 ℃ and the reaction time is 4h to 6 h.
In one embodiment, the reaction system contains an organic solvent.
In one embodiment, one skilled in the art can select a suitable organic solvent as desired. Therefore, the organic solvent is selected from at least one of a mixed solution of dioxane and acetonitrile, a mixed solution of dichloromethane and acetonitrile, a mixed solution of 1, 2-dichloroethane and acetonitrile, a mixed solution of carbon tetrachloride and acetonitrile, and pure acetonitrile.
In one embodiment, the reaction system contains an additive selected from at least one of toluenesulfonic acid hydrate, sulfuric acid, water, trifluoromethanesulfonic acid, and the like.
In one embodiment, the method for synthesizing the amide compound shown in the formula I at least comprises the following steps: reacting a compound II, a compound III, a compound IV and a solvent in a reaction system containing a catalyst containing ferric trifluoromethanesulfonate and an additive containing p-toluenesulfonic acid monohydrate at the temperature of 60-80 ℃ for 4-6 h under a stirring state, cooling to 20-30 ℃, removing the solvent through reduced pressure distillation, and performing column chromatography separation to obtain the amide compound shown in the formula I.
In the present invention, C1To C20、C1To C10、C6To C20、C3To C20And C1To C10And the like refer to the number of carbon atoms involved. The carbon atoms of the "substituted hydrocarbon group", "substituted aromatic hydrocarbon group" and "substituted heteroaryl group" are defined to mean the number of carbon atoms contained in the hydrocarbon group, aromatic hydrocarbon group and heteroaryl group, not the number of carbon atoms after substitution. Such as C1To C20The substituted hydrocarbon group of (1) means a hydrocarbon group having 1 to 20 carbon atoms, at least one hydrogen atom being substituted with a substituent.
In the present invention, the "non-hydrocarbon substituent" means a group formed by a compound containing an element other than H and C (e.g., halogen, S, O, P, N, etc.) by losing any one hydrogen atom.
In the present invention, the "hydrocarbon group" is a group formed by losing any one hydrogen atom on the molecule of the hydrocarbon compound; the hydrocarbon compounds include alkane compounds, alkene compounds, alkyne compounds, and aromatic hydrocarbon compounds. Such as p-tolyl group in which toluene loses the hydrogen atom para to the methyl group on the phenyl ring, or benzyl group in which toluene loses any of the hydrogen atoms on the methyl group, and the like.
In the present invention, the "alkyl group" is a group formed by losing any one hydrogen atom on the molecule of the alkane compound. The alkane compound comprises straight-chain alkane, branched-chain alkane, cycloalkane and cycloalkane with branched chain.
In the present invention, "aryl" is a group formed by losing one hydrogen atom on an aromatic ring on an aromatic compound molecule; such as p-tolyl, formed by toluene losing the hydrogen atom para to the methyl group on the phenyl ring.
In the present invention, the "heteroaryl" is a group formed by losing any one of hydrogen atoms on an aromatic ring on an aromatic compound (referred to as a "heteroaryl compound" for short) having O, N, S heteroatoms in the aromatic ring; such as piperazine ring, by the loss of any one of the hydrogen atoms.
In the present invention, the "halogen" refers to at least one of fluorine, chlorine, bromine and iodine.
In the present invention, the carbon atom definition of the "substituted hydrocarbon group", "substituted aryl group" and "substituted heteroaryl group" means that the hydrocarbon group, aryl group and heteroaryl group are defined as the hydrocarbon group, aryl group and heteroaryl group per seThe number of carbon atoms contained, not the number of carbon atoms after substitution. Such as C1To C20The substituted hydrocarbon group of (2) means a group having a carbon atom number of C1To C20At least one hydrogen atom on the hydrocarbon group of (1) is substituted with a substituent.
The beneficial effects of the invention include but are not limited to:
(1) according to the synthesis method of the amide compound, provided by the invention, the amide compound is prepared by taking an alkylating reagent as an alkyl electrophilic reagent for the first time.
(2) The synthesis method of the amide compound provided by the invention has the advantages of cheap raw materials and catalysts, mild reaction conditions, simple operation, high reaction efficiency and the like.
Detailed Description
The present invention will be described in detail with reference to examples, but the present invention is not limited to these examples.
The raw materials in the examples of the present invention were all purchased from commercial sources unless otherwise specified.
In the examples, NMR spectra1H-NMR was measured on a 400AVANCE model III Spectrometer (Spectrometer) from Bruker, 400MHz, CDCl3(ii) a Carbon spectrum13C-NMR，400MHz，CDCl3。
The product separation adopts an RF + UV-VIS type full-automatic rapid preparation chromatographic system of Teledyne Isco.
Electron impact Mass Spectrometry MS (EI) A6224 TOF type mass spectrometer from AGI L ENT was used.
DCC in the examples is dicyclohexylcarbodiimide; DMAP is 4-dimethylaminopyridine.
The room temperature in the examples means a temperature of 20 ℃ to 30 ℃.
The yield of the compound having a double bond is calculated by the following formula:
yield% × 100% ×% (mass of target product actually obtained ÷ mass of target product theoretically to be obtained).
Example 1
1.5mmol (1.5 equiv.) of styrene 1-1, 398mg (1mmol, 1 equiv.) of lauroyl peroxide 1-2, 4m L acetonitrile 1-3, 50.3mg of the catalyst Fe (OTf)3(10 mol%) 380mg of additive p-toluenesulfonic acid monohydrate TsOH H2O (2mmol, 2 equiv.) and 36mg H2O (2mmol, 2 equiv.) and a magnetic stirrer were added and then placed in a 70 ℃ oil bath for 5 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, the solvent was removed by distillation and concentration under reduced pressure, and the crude product was separated by column chromatography to obtain a sample of 1 to 4, which was 238.7mg in total, and the yield was 64%.
The nuclear magnetic data for product samples 1-4 are as follows:
1H NMR(400MHz,CDCl3)7.34(d,J＝8.0Hz,2H),7.21(d,J＝8.0Hz,2H),5.96(d,J＝36.0Hz,1H),4.94(dd,J1＝8.0Hz,J2＝16.0Hz,1H),1.95(s,3H),1.80-1.76(m,2H),1.30(s,9H),1.30-1.23(m,20H),0.88(t,J＝8.0Hz,3H).
13C NMR(100MHz,CDCl3)169.24,150.10,139.46,126.31,125.50,53.15,36.18,34.46,31.93,31.36,29.67,29.65,29.61,29.51,29.46,29.36,26.33,23.44,22.70,14.13.
example 2
1.5mmol (1.5 equiv.) of 2-methylstyrene 2-1, 398mg (1mmol, 1 equiv.) of lauroyl peroxide 2-2, 4m L acetonitrile 2-3, 50.3mg of the catalyst Fe (OTf)3(10 mol%) 380mg of additive p-toluenesulfonic acid monohydrate TsOH H2O (2mmol, 2 equiv.) and 36mg H2O (2mmol, 2 equiv.) and a magnetic stirrer were added and then placed in a 70 ℃ oil bath for 5 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, the solvent was removed by distillation and concentration under reduced pressure, and the crude product was separated by column chromatography to obtain a sample of 2 to 4, which was 277.3mg in total, and the yield was 84%.
The nuclear magnetic data for product samples 2-4 are as follows:
1H NMR(400MHz,CDCl3)7.22-7.14(m,4H),5.76(br,1H),5.19(dd,J1＝8.0Hz,J2＝16.0Hz,1H),2.39(s,3H),1.95(s,3H),1.81-1.72(m,2H),1.30-1.23(m,20H),0.88(t,J＝8.0Hz,3H).
13C NMR(100MHz,CDCl3)169.05,140.69,136.20,130.70,127.10,126.23,124.91,49.50,36.01,31.92,29.66,29.64,29.59,29.53,29.50,29.35,26.31,23.36,22.69,19.45,14.12.
example 3
1.5mmol (1.5 equiv.) of the olefinic compound 3-1, 398mg (1mmol, 1 equiv.) of lauroyl peroxide 3-2, 4m L acetonitrile 3-3, 50.3mg of the catalyst Fe (OTf)3(10 mol%) 380mg of additive p-toluenesulfonic acid monohydrate TsOH H2O (2mmol, 2 equiv.) and 36mg H2O (2mmol, 2 equiv.) and a magnetic stirrer were added and then placed in a 70 ℃ oil bath for 5 hours. After the reaction, the reaction mixture was cooled to room temperature, the solvent was removed by distillation and concentration under reduced pressure, and the crude product was separated by column chromatography to obtain a sample of 3-4, which was 230.3mg in total, giving a yield of 67%.
The nuclear magnetic data for product samples 3-4 are as follows:
1H NMR(400MHz,CDCl3)7.05(t,J＝8.0Hz,2H),6.97(d,J＝8.0Hz,1H),5.73-5.68(m,1H),5.16(dd,J1＝8.0Hz,J2＝16.0Hz,1H),2.34(s,3H),2.31(s,3H),1.95(s,3H),1.79-1.70(m,2H),1.30-1.23(m,20H),0.88(t,J＝8.0Hz,3H).
13C NMR(100MHz,CDCl3)169.00,140.48,135.58,133.00,130.61,127.83,125.64,49.51,36.10,31.93,29.67,29.64,29.60,29.53,29.50,29.36,26.32,23.41,22.70,21.17,19.00,14.12.
example 4
1.5mmol (1.5 equiv.) of the olefinic compound 4-1, 398mg (1mmol, 1 equiv.) of peroxy-monthlyLauroyl 4-2, 4m L acetonitrile 4-3, 50.3mg catalyst Fe (OTf)3(10 mol%) 380mg of additive p-toluenesulfonic acid monohydrate TsOH H2O (2mmol, 2 equiv.) and 36mg H2O (2mmol, 2 equiv.) and a magnetic stirrer were added and then placed in a 70 ℃ oil bath for 5 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, the solvent was removed by distillation and concentration under reduced pressure, and the crude product was separated by column chromatography, and a sample of the obtained product was recorded as 4 to 4, which amounted to 277.5mg, giving a yield of 79%.
The nuclear magnetic data for product samples 4-4 are as follows:
1H NMR(400MHz,CDCl3)7.29(d,J＝8.0Hz,2H),7.21(d,J＝8.0Hz,2H),5.96(d,J＝8.0Hz,1H),4.89(dd,J1＝8.0Hz,J2＝16.0Hz,1H),1.96(s,3H),1.76-1.71(m,2H),1.34-1.23(m,20H),0.88(t,J＝8.0Hz,3H).
13C NMR(100MHz,CDCl3)169.35,141.18,132.90,128.71,127.97,52.97,36.12,31.91,29.64,29.63,29.61,29.55,29.46,29.34,26.19,23.33,22.68,14.11.
example 5
1.5mmol (1.5 equiv.) of olefinic compound 5-1, 398mg (1mmol, 1 equiv.) of lauroyl peroxide 5-2, 4m L acetonitrile 5-3, 50.3mg of catalyst Fe (OTf)3(10 mol%) 380mg of additive p-toluenesulfonic acid monohydrate TsOH H2O (2mmol, 2 equiv.) and 36mg H2O (2mmol, 2 equiv.) and a magnetic stirrer were added and then placed in a 70 ℃ oil bath for 5 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, the solvent was removed by distillation and concentration under reduced pressure, and the crude product was separated by column chromatography to obtain a sample of 5 to 4, which was 261.5mg in total, in a yield of 72%.
The nuclear magnetic detection data for product samples 5-4 are as follows:
1H NMR(400MHz,CDCl3)7.35(d,J＝8.0Hz,2H),7.27(d,J＝8.0Hz,2H),5.84(br,1H),4.94(dd,J1＝8.0Hz,J2＝16.0Hz,1H),4.56(s,2H),1.96(s,3H),1.78-1.73(m,2H),1.29-1.23(m,20H),0.88(t,J＝8.0Hz,3H).
13C NMR(100MHz,CDCl3)169.26,142.92,136.45,128.89,126.98,53.23,45.94,36.15,31.92,29.65,29.64,29.62,29.57,29.47,29.39,29.35,26.23,23.42,22.69,14.12.
example 6
1.5mmol (1.5 equiv.) of the olefinic compound 6-1, 398mg (1mmol, 1 equiv.) of lauroyl peroxide 6-2, 4m L acetonitrile 6-3, 50.3mg of the catalyst Fe (OTf)3(10 mol%) 380mg of additive p-toluenesulfonic acid monohydrate TsOH H2O (2mmol, 2 equiv.) and 36mg H2O (2mmol, 2 equiv.) and a magnetic stirrer were added and then placed in a 70 ℃ oil bath for 5 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, the solvent was removed by distillation and concentration under reduced pressure, and the crude product was separated by column chromatography, and a sample of the obtained product was recorded as 6-4, 269.5mg in total, and the yield was 70%.
The nuclear magnetic detection data of the product sample 6-4 is as follows:
1H NMR(400MHz,CDCl3)7.51-7.40(m,4H),6.05(d,J＝8.0Hz,1H),4.99(dd,J1＝8.0Hz,J2＝16.0Hz,1H),1.98(s,3H),1.78-1.73(m,2H),1.34-1.21(m,20H),0.88(d,J＝8.0Hz,3H).
13C NMR(100MHz,CDCl3)169.50,143.86,131.05(2JC-F＝32Hz),130.25,129.01,125.47(1JC-F＝270Hz),124.05(3JC-F＝4Hz),123.01(3JC-F＝4Hz),53.23,36.24,31.92,29.65,29.63,29.61,29.54,29.44,29.35,29.30,26.20,23.28,22.69,14.11.
19F NMR(376MHz,CDCl3)-62.51.
example 7
1.5mmol (1.5 equiv) of olefins were added to the reaction tubeCompound 7-1, 398mg (1mmol, 1 equiv.) of lauroyl peroxide 7-2, 4m L acetonitrile 7-3, 50.3mg of catalyst Fe (OTf)3(10 mol%) 380mg of additive p-toluenesulfonic acid monohydrate TsOH H2O (2mmol, 2 equiv.) and 36mg H2O (2mmol, 2 equiv.) and a magnetic stirrer were added and then placed in a 70 ℃ oil bath for 5 hours. After the reaction, the reaction mixture was cooled to room temperature, the solvent was removed by distillation and concentration under reduced pressure, and the crude product was separated by column chromatography to obtain a sample of 7-4, 204.6mg in total, which was 60%.
The nuclear magnetic detection data for product sample 7-4 is as follows:
1H NMR(400MHz,CDCl3)7.50(d,J＝8.0Hz,1H),7.32-7.24(m,2H),7.21-7.17(m,1H),6.45(d,J＝8.0Hz,1H),5.24(dd,J1＝8.0Hz,J2＝16.0Hz,1H),3.38(s,1H),1.97(s,3H),1.86-1.79(m,2H),1.29-1.23(m,20H),0.88(d,J＝8.0Hz,3H).
13C NMR(100MHz,CDCl3)169.24,145.10,133.89,129.12,127.00,126.88,120.06,82.39,82.26,52.99,35.37,31.92,29.67,29.64,29.59,29.49,29.36,29.34,26.44,23.35,22.69,14.13.
example 8
1.5mmol (1.5 equiv.) of the olefinic compound 8-1, 398mg (1mmol, 1 equiv.) of lauroyl peroxide 8-2, 4m L acetonitrile 8-3, 50.3mg of the catalyst Fe (OTf)3(10 mol%) 380mg of additive p-toluenesulfonic acid monohydrate TsOH H2O (2mmol, 2 equiv.) and 36mg H2O (2mmol, 2 equiv.) and a magnetic stirrer were added and then placed in a 70 ℃ oil bath for 5 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, the solvent was removed by distillation and concentration under reduced pressure, and the crude product was separated by column chromatography, and a sample of the obtained product was recorded as 8-4, which amounted to 285.1mg, giving a yield of 73%.
The nuclear magnetic detection data for product sample 8-4 is as follows:
1H NMR(400MHz,CDCl3)7.57-7.53(m,4H),7.41(t,J＝8.0Hz,2H),7.35-7.32(m,3H),5.98(d,J＝8.0Hz,1H),4.98(dd,J1＝8.0Hz,J2＝16.0Hz,1H),1.97(s,3H),1.80-1.78(m,2H),1.28-1.24(m,20H),0.87(t,J＝8.0Hz,3H).
13C NMR(100MHz,CDCl3)169.33,141.64,140.79,140.22,128.78,127.37,127.28,127.06,126.98,53.29,36.24,31.94,29.69,29.67,29.62,29.53,29.46,29.38,26.33,23.46,22.71,14.14.
example 9
1.5mmol (1.5 equiv.) of the olefinic compound 9-1, 398mg (1mmol, 1 equiv.) of lauroyl peroxide 9-2, 4m L acetonitrile 9-3, 50.3mg of the catalyst Fe (OTf)3(10 mol%) 380mg of additive p-toluenesulfonic acid monohydrate TsOH H2O (2mmol, 2 equiv.) and 36mg H2O (2mmol, 2 equiv.) and a magnetic stirrer were added and then placed in a 70 ℃ oil bath for 5 hours. After the reaction was complete, the reaction mixture was cooled to room temperature, concentrated under reduced pressure to remove the solvent, and the crude product was isolated by column chromatography, giving a sample of 9-4, total 269.1mg, 73% yield.
The nuclear magnetic data for product sample 9-4 is as follows:
1H NMR(400MHz,CDCl3)7.79-7.76(m,3H),7.71(s,1H),7.45-7.42(m,2H),7.39-7.36(m,1H),6.20(d,J＝8.0Hz,1H),5.10(dd,J1＝8.0Hz,J2＝16.0Hz,1H),1.94(s,3H),1.87-1.80(m,2H),1.29-1.22(m,20H),0.87(t,J＝8.0Hz,3H).
13C NMR(100MHz,CDCl3)169.41,139.96,133.39,132.76,128.46,127.89,127.64,126.18,125.81,125.35,124.86,53.68,36.18,31.95,29.67,26.35,23.43,22.72,14.16.
example 10
1.5mmol (1.5 equivalent) of olefin compound 10-1, 398mg (1mmol, 1 equivalent) of lauroyl peroxide 10-2, 4m L acetonitrile 10-3, 50.3mg of catalyst are added into a reaction tubeAgents Fe (OTf)3(10 mol%) 380mg of additive p-toluenesulfonic acid monohydrate TsOH H2O (2mmol, 2 equiv.) and 36mg H2O (2mmol, 2 equiv.) and a magnetic stirrer were added and then placed in a 70 ℃ oil bath for 5 hours. After the reaction was complete, the reaction mixture was cooled to room temperature, concentrated under reduced pressure to remove the solvent, and the crude product was isolated by column chromatography, giving a sample of 10-4 as 266.2mg in 52% yield.
The nuclear magnetic data for the product sample 10-4 is as follows:
1H NMR(400MHz,CDCl3)7.41-7.39(m,2H),7.29-7.28(m,2H),6.08-6.05(m,1H),4.97(dd,J1＝8.0Hz,J2＝16.0Hz,1H),2.01(s,3H),1.76-1.69(m,2H),1.50-1.44(m,2H),1.30-1.26(m,2H),0.88(t,J＝8.0Hz,3H).
13C NMR(100MHz,CDCl3)169.05,131.71,128.26,122.77,88.72,88.94,42.07,36.11,31.92,29.68,29.65,29.58,29.53,29.36,29.20,25.76,23.25,22.69,14.12.
example 11
1.5mmol (1.5 equiv.) of the olefinic compound 11-1, 398mg (1mmol, 1 equiv.) of lauroyl peroxide 11-2, 4m L acetonitrile 11-3, 50.3mg of the catalyst Fe (OTf)3(10 mol%) 380mg of additive p-toluenesulfonic acid monohydrate TsOH H2O (2mmol, 2 equiv.) and 36mg H2O (2mmol, 2 equiv.) and a magnetic stirrer were added and then placed in a 70 ℃ oil bath for 5 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, the solvent was removed by distillation and concentration under reduced pressure, and the crude product was separated by column chromatography, whereby a sample of the obtained product was recorded as 11-4, which amounted to 124.6mg, and the yield was 30%.
The nuclear magnetic data for product sample 11-4 is as follows:
1H NMR(400MHz,CDCl3)7.62-7.57(m,3H),7.47(d,J＝8.0Hz,1H),7.32(t,J＝8.0Hz,2H),7.21-7.15(m,4H),7.10-7.06(m,1H),5.41(dd,J1＝4.0Hz,J2＝8.0Hz,1H),3.95-3.90(m,1H),2.11(s,3H),1.81-1.71(m,2H),1.47-1.43(m,1H),1.34-1.22(m,19H),0.88(t,J＝8.0Hz,3H).
13C NMR(100MHz,CDCl3)206.18,169.83,141.18,137.53,133.37,128.55,128.46,128.04,127.12,126.11,54.06,50.12,31.90,31.52,29.59,29.56,29.52,29.33,29.31,27.60,23.50,22.69,14.12.
example 12
1.5mmol (1.5 equiv.) of the olefinic compound 12-1, 398mg (1mmol, 1 equiv.) of lauroyl peroxide 12-2, 4m L acetonitrile 12-3, 50.3mg of the catalyst Fe (OTf)3(10 mol%) 380mg of additive p-toluenesulfonic acid monohydrate TsOH H2O (2mmol, 2 equiv.) and 36mg H2O (2mmol, 2 equiv.) and a magnetic stirrer were added and then placed in a 70 ℃ oil bath for 5 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, the solvent was removed by concentration under reduced pressure, and the crude product was separated by column chromatography to obtain a sample of 12-4 (259.6 mg total), which was 44%.
The NMR data for product sample 12-4 are as follows:
1H NMR(400MHz,CDCl3)7.25-7.13(m,6H),6.95-6.90(m,4H),5.96(d,J＝8.0Hz,1H),5.23(t,J＝8.0Hz,1H),3.01-2.95(m,1H),1.98(s,3H),1.85-1.78(m,1H),1.66-1.60(m,1H),1.28-1.17(m,20H),0.87(t,J＝8.0Hz,3H).
13C NMR(100MHz,CDCl3)169.18,140.49,140.06,129.05,128.02,127.97,127.59,127.12,126.57,57.75,51.16,32.12,31.91,29.66,29.61,29.58,29.49,29.34,27.50,23.54,22.69,14.12.
example 13
1.5mmol (1.5 equiv.) of the olefinic compound 13-1, 398mg (1mmol, 1 equiv.) of lauroyl peroxide 13-2, 4m L acetonitrile 13-3, 50.3mg of the catalyst Fe (OTf)3(10 mol%) 380mg of additive p-toluenesulfonic acid oneHydrate TsOH. H2O (2mmol, 2 equiv.) and 36mg H2O (2mmol, 2 equiv.) and a magnetic stirrer were added and then placed in a 70 ℃ oil bath for 5 hours. After the reaction was complete, the reaction mixture was cooled to room temperature, concentrated by distillation under reduced pressure to remove the solvent, and the crude product was isolated by column chromatography, giving a sample of 13-4 as 218.7mg in total, giving a yield of 44%.
The nuclear magnetic data for the product sample 13-4 is as follows:
1H NMR(400MHz,CDCl3)7.33-7.29(m,2H),7.25-7.21(m,3H),5.93(d,J＝8.0Hz,1H),4.82(t,J＝8.0Hz,1H),1.99(s,3H),1.88-1.81(m,1H),1.28-1.25(m,20H),0.88(t,J＝8.0Hz,3H),0.80(d,J＝8.0Hz,3H).
13C NMR(100MHz,CDCl3)169.38,141.50,128.42,127.06,58.28,38.16,32.58,31.92,29.87,29.68,29.64,29.36,27.13,23.49,22.69,16.54,14.12.
example 14
1.5mmol (1.5 equiv.) of the olefinic compound 14-1, 398mg (1mmol, 1 equiv.) of lauroyl peroxide 14-2, 4m L acetonitrile 14-3, 50.3mg of the catalyst Fe (OTf)3(10 mol%) 380mg of additive p-toluenesulfonic acid monohydrate TsOH H2O (2mmol, 2 equiv.) and 36mg H2O (2mmol, 2 equiv.) and a magnetic stirrer were added and then placed in a 70 ℃ oil bath for 5 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, the solvent was removed by distillation and concentration under reduced pressure, and the crude product was separated by column chromatography, and a sample of the obtained product was taken as 14-4, and 244.2mg in total, and the yield was 33%.
The nuclear magnetic data for product sample 14-4 is as follows:
1H NMR(400MHz,CDCl3)7.26(d,J＝8.0Hz,1H),7.07(d,J＝8.0Hz,1H),7.01(s,1H),5.89(d,J＝8.0Hz,1H),4.90(dd,J1＝8.0Hz,J2＝16.0Hz,1H),2.91(dd,J1＝4.0Hz,J2＝8.0Hz,2H),2.54-2.47(m,1H),2.43-2.39(m,1H),2.30-2.25(m,1H),2.18-2.09(m,1H),2.06-1.99(m,2H),1.96(s,3H),1.95-1.94(m,1H),1.80-1.74(m,2H),1.66-1.56(m,2H),1.55-1.44(m,4H),1.29-1.24(m,20H),0.92-0.86(m,6H).
13C NMR(100MHz,CDCl3)220.85,169.14,140.02,138.77,136.72,127.54,127.34,125.62,123.86,123.70,53.18,53.14,50.53,47.99,44.37,44.35,38.13,36.21,36.17,35.86,31.92,31.61,29.67,29.64,29.60,29.49,29.44,29.35,26.51,26.33,25.69,23.51,22.69,21.59,14.12,13.86.
example 15
1.5mmol (1.5 equiv.) of olefinic compound 15-1, 398mg (1mmol, 1 equiv.) of lauroyl peroxide 15-2, 4m L acetonitrile 15-3, 50.3mg of catalyst Fe (OTf)3(10 mol%) 380mg of additive p-toluenesulfonic acid monohydrate TsOH H2O (2mmol, 2 equiv.) and 36mg H2O (2mmol, 2 equiv.) and a magnetic stirrer were added and then placed in a 70 ℃ oil bath for 5 hours. After the reaction, the reaction mixture was cooled to room temperature, the solvent was removed by distillation and concentration under reduced pressure, and the crude product was separated by column chromatography, and the obtained sample was 15-4 mg in total, which was 314.4mg, and the yield was 60%.
The nuclear magnetic data for product sample 15-4 is as follows:
1H NMR(400MHz,CDCl3)7.01-6.94(m,2H),6.84(t,J＝8.0Hz,1H),6.13(d,J＝8.0Hz,1H),4.79(dd,J1＝8.0Hz,J2＝16.0Hz,1H),2.16(s,3H),1.87(s,3H),1.68-1.69(m,2H),1.20-1.15(m,20H),0.80(t,J＝8.0Hz,3H).
13C NMR(100MHz,CDCl3)169.31,161.62(1JC-F＝242Hz),138.20(3JC-F＝3Hz),129.82(3JC-F＝5Hz),125.27(3JC-F＝8Hz),124.87(2JC-F＝17Hz),115.05(2JC-F＝22Hz),52.96,36.33,31.92,29.66,29.64,29.58,29.50,29.39,29.35,26.30,23.33,22.69,14.63(3JC-F＝4Hz),14.11.
example 16
73.3mg DMAP (0.6mmol), 7.5m L CH were added to the reaction tube2Cl2Cooled to-15 ℃ and then 0.9m L H was added2O2(8mmol), 1.483g (7.2mmol) of DCC and 6mmol of acid 16-1, a magnetic stirrer was added and the reaction was carried out at-10 to-15 ℃ for 1.5 hours. After the reaction is finished, cooling to room temperature, carrying out reduced pressure distillation and concentration to remove the solvent, and separating the crude product by column chromatography to obtain the peroxide 16-2.
2mmol (1 eq) of styrene 16-3, 3mmol (1.5 eq) of peroxide 16-2, 8m L of acetonitrile 16-4, 100.6mg of catalyst Fe (OTf)3(10 mol%) 760mg of additive p-toluenesulfonic acid monohydrate TsOH H2O (4mmol, 2 equiv.) and 72mg H2O (2mmol, 2 equiv.) and a magnetic stirrer were added and then placed in a 70 ℃ oil bath for 5 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, the solvent was removed by distillation and concentration under reduced pressure, and the crude product was separated by column chromatography to obtain a sample of 16-5, 184mg in total, and 79% yield.
The nuclear magnetic data for the product sample 16-5 are as follows:
1H NMR(400MHz,CDCl3)7.30-7.22(m,5H),6.36(d,J＝8.0Hz,1H),4.93(dd,J1＝8.0Hz,J2＝16.0Hz,1H),1.93(s,3H),1.77-1.73(m,2H),1.27-1.23(m,8H),0.85(t,J＝8.0Hz,3H).
13C NMR(100MHz,CDCl3)169.96,143.20,128.43,126.98,126.70,53.70,36.51,31.78,29.14,26.43,23.03,22.65,14.11.
example 17
73.3mg DMAP (0.6mmol), 7.5m L CH were added to the reaction tube2Cl2Cooled to-15 ℃ and then 0.9m L H was added2O2(8mmol), 1.483g (7.2mmol) of DCC and 6mmol of acid 17-1, a magnetic stirrer was added and the reaction was carried out at-10 to-15 ℃ for 1.5 hours. After the reaction is finished, cooling to room temperature, carrying out reduced pressure distillation and concentration to remove the solvent, and separating the crude product by column chromatography to obtain the peroxide 17-2.
2mmol (1 eq) of styrene 17-3, 3mmol (1.5 eq) of peroxide 17-2, 8m L of acetonitrile 17-4, 100.6mg of catalyst Fe (OTf)3(10 mol%) 760mg of additive p-toluenesulfonic acid monohydrate TsOH H2O (4mmol, 2 equiv.) and 72mg H2O (2mmol, 2 equiv.) and a magnetic stirrer were added and then placed in a 70 ℃ oil bath for 5 hours. After the reaction, the reaction mixture was cooled to room temperature, the solvent was removed by distillation and concentration under reduced pressure, and the crude product was separated by column chromatography to obtain a sample of 17-5, 368.4mg in total, and the yield was 79%.
The nuclear magnetic assay data for product sample 17-5 are as follows:
1H NMR(400MHz,CDCl3)7.32-7.26(m,5H),6.13(d,J＝8.0Hz,1H),4.90(dd,J1＝8.0Hz,J2＝16.0Hz,1H),1.95(s,3H),1.79-1.73(m,2H),1.26-1.22(m,1H),1.11-1.07(m,1H),0.85(s,9H).
13C NMR(100MHz,CDCl3)169.30,142.58,128.62,127.26,126.64,54.19,40.33,31.33,30.11,29.31,23.40.
example 18
73.3mg DMAP (0.6mmol), 7.5m L CH were added to the reaction tube2Cl2Cooled to-15 ℃ and then 0.9m L H was added2O2(8mmol), 1.483g (7.2mmol) of DCC and 6mmol of acid 18-1, a magnetic stirrer was added and the reaction was carried out at-10 to-15 ℃ for 1.5 hours. After the reaction is finished, cooling to room temperature, carrying out reduced pressure distillation and concentration to remove the solvent, and separating the crude product by column chromatography to obtain the peroxide 18-2.
2mmol (1 eq) of styrene 18-3, 3mmol (1.5 eq) of peroxide 18-2, 8m L of acetonitrile 18-4, 100.6mg of catalyst Fe (OTf)3(10 mol%) 760mg of additive p-toluenesulfonic acid monohydrate TsOH H2O (4mmol, 2 equiv.) and 72mg H2O (2mmol, eq.) was added with a magnetic stirrer and then placed in a 70 ℃ oil bath for 5 hours. Cooling to room temperature after the reaction is finished, and distilling under reduced pressureThe solvent was removed by concentration and the crude product was column chromatographed, giving a sample of 18-5, 191.6mg total, 74% yield.
The nuclear magnetic data for product sample 18-5 is as follows:
1H NMR(400MHz,CDCl3)7.31-7.25(m,5H),6.16(d,J＝8.0Hz,1H),4.95(dd,J1＝8.0Hz,J2＝16.0Hz,1H),1.94(s,3H),1.78-1.74(m,2H),1.73-1.64(m,3H),1.58-1.52(m,2H),1.50-1.45(m,2H),1.34-1.23(m,4H),1.02-1.00(m,2H).
13C NMR(100MHz,CDCl3)169.30,142.62,128.57,127.21,126.61,53.51,39.95,36.48,35.88,32.68,32.63,25.43,25.14,23.38.
example 19
1.5mmol (1.5 equiv.) of styrene 19-1, 1mmol (1 equiv.) of peroxoacyl 19-2, 4m L nitrile 19-3, 50.3mg of catalyst Fe (OTf)3(10 mol%) 380mg of additive p-toluenesulfonic acid monohydrate TsOH H2O (2mmol, 2 equiv.) and 36mg H2O (2mmol, 2 equiv.) and a magnetic stirrer were added and then placed in a 70 ℃ oil bath for 5 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, the solvent was removed by distillation and concentration under reduced pressure, and the crude product was separated by column chromatography, whereby a sample of the obtained product was taken as 19-4, and 153.4mg in total, and the yield was 52%.
The NMR data for product sample 19-4 are as follows:
1H NMR(400MHz,CDCl3)7.76(d,J＝8.0Hz,2H),7.43(t,J＝8.0Hz,1H),7.37-7.28(m,6H),7.25-7.21(m,1H),6.70(d,J＝8.0Hz,1H),5.15(dd,J1＝8.0Hz,J2＝16.0Hz,1H),1.92-1.84(m,2H),1.30-1.22(m,8H),0.85(t,J＝8.0Hz,3H).
13C NMR(100MHz,CDCl3)166.90,142.69,134.77,131.33,128.64,128.46,127.26,127.25,127.10,127.07,126.70,54.06,36.35,31.74,29.13,26.43,26.41,22.63,14.10.
example 20
73.3mg DMAP (0.6mmol), 7.5m L CH were added to the reaction tube2Cl2Cooled to-15 ℃ and then 0.9m L H was added2O2(8mmol), 1.483g (7.2mmol) of DCC and 6mmol of acid 20-1, a magnetic stirrer was added and the reaction was carried out at-10 to-15 ℃ for 1.5 hours. After the reaction is finished, cooling to room temperature, carrying out reduced pressure distillation and concentration to remove the solvent, and separating the crude product by column chromatography to obtain the peroxide 20-2.
2mmol (1 equiv.) of styrene 20-3, 3mmol (1.5 equiv.) of peroxide 20-2, 8m L of acetonitrile 20-4, 100.6mg of catalyst Fe (OTf)3(10 mol%) 760mg of additive p-toluenesulfonic acid monohydrate TsOH H2O (4mmol, 2 equiv.) and 72mg H2O (2mmol, 2 equiv.) and a magnetic stirrer were added and then placed in a 70 ℃ oil bath for 5 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, the solvent was removed by distillation and concentration under reduced pressure, and the crude product was separated by column chromatography, and a total of 191.6mg of the product was obtained as 20 to 5, with a yield of 74%.
The nuclear magnetic detection data of the product sample 20-5 are as follows:
1H NMR(400MHz,CDCl3)7.32(t,J＝8.0Hz,2H),7.25-7.21(m,5H),7.17(d,J＝8.0Hz,1H),7.13(d,J＝8.0Hz,2H),6.05(br,1H),4.94(dd,J1＝8.0Hz,J2＝16.0Hz,1H),2.55(t,J＝8.0Hz,2H),1.92(s,3H),1.84-1.73(m,2H),1.65-1.58(m,2H),1.40-1.23(m,2H).
13C NMR(100MHz,CDCl3)169.41,142.50,142.42,128.66,128.40,128.32,127.33,126.63,125.73,53.49,36.07,35.73,31.16,25.90,23.37.
example 21
73.3mg DMAP (0.6mmol), 7.5m L CH were added to the reaction tube2Cl2Cooled to-15 ℃ and then 0.9m L H was added2O2(8mmol), 1.483g (7.2mmol) of DCC and 6mmol of acid 21-1, a magnetic stirrer was added and the reaction was carried out at-10 to-15 ℃ for 1.5 hours. After the reaction is finished, cooling to room temperature, carrying out reduced pressure distillation and concentration to remove the solvent, and separating the crude product by column chromatography to obtain the peroxide 21-2.
2mmol (1 eq) of styrene 21-3, 3mmol (1.5 eq) of peroxide 21-2, 8m L of acetonitrile 21-4, 100.6mg of catalyst Fe (OTf)3(10 mol%) 760mg of additive p-toluenesulfonic acid monohydrate TsOH H2O (4mmol, 2 equiv.) and 72mg H2O (2mmol, 2 equiv.) and a magnetic stirrer were added and then placed in a 70 ℃ oil bath for 5 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, the solvent was removed by distillation and concentration under reduced pressure, and the crude product was separated by column chromatography to obtain a sample of 21-5, 374.6mg in total, giving a yield of 74%.
The nuclear magnetic assay data for product samples 21-5 are as follows:
1H NMR(400MHz,CDCl3)7.33-7.23(m,5H),6.21(br,1H),4.94(dd,J1＝8.0Hz,J2＝16.0Hz,1H),3.48(t,J＝8.0Hz,2H),1.94(s,3H),1.82-1.69(m,4H),1.47-1.40(m,2H),1.37-1.21(m,2H).
13C NMR(100MHz,CDCl3)169.44,142.33,128.67,127.37,126.61,53.44,44.96,36.04,32.40,26.62,25.59,23.35.
example 22
1.5mmol (1.5 equiv.) of styrene 22-1, 262.1mg (1mmol, 1 equiv.) of peroxide 22-2, 4m L acetonitrile 22-3, 50.3mg of catalyst Fe (OTf)3(10 mol%) 380mg of additive p-toluenesulfonic acid monohydrate TsOH H2O (2mmol, 2 equiv.) and 36mg H2O (2mmol, 2 equiv.) and a magnetic stirrer were added and then placed in a 70 ℃ oil bath for 5 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, the solvent was removed by distillation and concentration under reduced pressure, and the crude product was separated by column chromatography, whereby a sample of 22-4 was obtained, which amounted to 171.9mg and gave a yield of 46%.
The nuclear magnetic data for product sample 22-4 is as follows:
1H NMR(400MHz,CDCl3)7.31-7.22(m,5H),6.71(br,1H),4.94(dd,J1＝8.0Hz,J2＝16.0Hz,1H),3.63(s,3H),2.30(t,J＝8.0Hz,2H),1.92(s,3H),1.82-1.75(m,2H),1.69-1.53(m,2H).
13C NMR(100MHz,CDCl3)173.88,169.74,142.22,128.61,127.32,126.54,53.18,51.54,35.47,33.52,23.17,21.60.
example 23
1mmol (1 equiv.) of styrene 23-1, 297.15mg (1.5mmol, 1.5 equiv.) of peroxide 23-2, 4m L acetonitrile 23-3, 50.3mg of catalyst Fe (OTf)3(10 mol%) 380mg of additive p-toluenesulfonic acid monohydrate TsOH H2O (2mmol, 2 equiv.) and 36mg H2O (2mmol, 2 equiv.) and a magnetic stirrer were added and then placed in a 70 ℃ oil bath for 5 hours. After the reaction, the reaction mixture was cooled to room temperature, the solvent was removed by distillation and concentration under reduced pressure, and the crude product was separated by column chromatography to obtain a sample of 23-4, 65.15mg in total, which was 30% yield.
The nuclear magnetic data for product sample 23-4 is as follows:
1H NMR(400MHz,CDCl3)7.33(t,J＝8.0Hz,2H),7.28(d,J＝8.0Hz,3H),5.80-5.70(m,2H),5.01-4.93(m,3H),2.07(dd,J1＝8.0Hz,J2＝16.0Hz,2H),1.97(s,3H),1.82-1.73(m,3H),1.45-1.39(m,1H).
13C NMR(100MHz,CDCl3)169.46,142.36,138.29,128.63,127.32,126.59,114.87,53.45,35.61,33.40,25.51,23.34.
example 24
1mmol (1 eq) of styrene 23-1, 3mmol (1.5 eq) of peroxyester 24-2, 4m L of acetonitrile 24-3, 50.3mg of catalyst were added to the reaction tubeAgent Fe (OTf)3(10 mol%) 380mg of additive p-toluenesulfonic acid monohydrate TsOH H2O (2mmol, 2 equiv.) and 36mg H2O (2mmol, 2 equiv.) and a magnetic stirrer were added and then placed in a 70 ℃ oil bath for 5 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, the solvent was removed by distillation and concentration under reduced pressure, and the crude product was separated by column chromatography to obtain a sample of 24-4, 158.5mg in total, 83% yield.
The nuclear magnetic data for product sample 24-4 is as follows:
1H NMR(400MHz,CDCl3)7.33-7.22(m,5H),6.15(d,J＝4.0Hz,1H),4.96(dd,J1＝8.0Hz,J2＝16.0Hz,1H),1.95(s,3H),1.79-1.69(m,2H),1.38-1.20(m,2H),0.91(t,J＝8.0Hz,3H).
13C NMR(100MHz,CDCl3)169.42,142.63,128.58,127.22,126.61,53.30,38.41,23.34,19.51,13.84.
example 25
1.5mmol (1.5 equiv.) of styrene 25-1, 1mmol (1 equiv.) of peroxoacyl 25-2, 4m L nitrile 25-3, 50.3mg of catalyst Fe (OTf)3(10 mol%) 380mg of additive p-toluenesulfonic acid monohydrate TsOH H2O (2mmol, 2 equiv.) and 36mg H2O (2mmol, 2 equiv.) and a magnetic stirrer were added and then placed in a 70 ℃ oil bath for 5 hours. After the reaction was complete, the reaction mixture was cooled to room temperature, concentrated under reduced pressure to remove the solvent, and the crude product was isolated by column chromatography, giving a sample of 25-4, total 170.9mg, 66% yield.
The nuclear magnetic data for product sample 25-4 is as follows:
1H NMR(400MHz,CDCl3)7.31-7.22(m,5H),6.29-6.25(m,1H),4.98(dd,J1＝8.0Hz,J2＝16.0Hz,1H),1.79-1.75(m,2H),1.35-1.20(m,9H),0.95-0.83(m,5H),0.70-0.63(m,2H).
13C NMR(100MHz,CDCl3)172.79,142.83,142.82,128.55,127.12,126.61,53.66,36.47,31.71,29.09,26.27,22.59,14.75,14.06,7.07,7.04.
example 26
1.5mmol (1.5 equiv.) of styrene 26-1, 398mg (1mmol, 1 equiv.) of lauroyl peroxide 26-2, 4m L acetonitrile 26-3, 19.5mg of catalyst FeCl are added into the reaction tube2(10 mol%) 380mg of additive p-toluenesulfonic acid monohydrate TsOH H2O (2mmol, 2 equiv.) and 36mg H2O (2mmol, 2 equiv.) and a magnetic stirrer were added and then placed in a 70 ℃ oil bath for 5 hours. After the reaction was completed, the reaction mixture was cooled to room temperature, the solvent was removed by distillation and concentration under reduced pressure, and the crude product was separated by column chromatography, and the obtained sample was recorded as 2 to 4, 361.7mg in total, and the yield was 76%.
The nuclear magnetic data for product sample 26-4 is as follows:
1H NMR(400MHz,CDCl3)7.34-7.24(m,5H),5.84(d,J＝8.0Hz,1H),4.97(dd,J1＝8.0Hz,J2＝16.0Hz,1H),1.96(s,3H),1.78-1.76(m,2H),1.25-1.23(m,20H),0.88(t,J＝8.0Hz,3H).
13C NMR(100MHz,CDCl3)169.18,142.50,128.62,127.27,126.59,53.54,36.23,31.92,29.66,29.64,29.62,29.57,29.48,29.41,29.35,26.25,23.46,22.69,14.12.
example 27
1.5mmol (1.5 equiv.) of styrene 27-1, 398mg (1mmol, 1 equiv.) of lauroyl peroxide 27-2, 4m L of acetonitrile 27-3, 22.8mg of catalyst FeSO are added to the reaction tube4(10 mol%), 300.16mg of additive trifluoromethanesulfonic acid (2mmol, 2 equiv.) and 36mg of H2O (2mmol, 2 equivalents), a magnetic stirrer was added, and then the mixture was put into a 90 ℃ oil bath to react for 7 hours. After the reaction was complete, the reaction mixture was cooled to room temperature, concentrated under reduced pressure to remove the solvent, and the crude product was isolated by column chromatography, giving a sample of 27-4, total 333.1mg, at 70% yield.
The NMR data of product sample 27-4 was substantially the same as that of product sample 26-4.
Example 28
A reaction tube was charged with a mixture of 1.5mmol (1.5 equiv.) of styrene 28-1, 398mg (1mmol, 1 equiv.) of lauroyl peroxide 28-2, 4m L acetonitrile 28-3 and dioxane, 50.3mg of the catalyst Fe (OTf)3(10 mol%), 196mg additive sulfuric acid (2mmol, 2 equiv.) and 36mg H2O (2mmol, 2 equivalents), a magnetic stirrer was added, and then the mixture was put into an oil bath at 25 ℃ for reaction for 1 hour. After the reaction was complete, the reaction mixture was cooled to room temperature, concentrated under reduced pressure to remove the solvent, and the crude product was isolated by column chromatography, giving a sample of 28-4 as 333.1mg in 68% yield.
The NMR data for product sample 28-4 was substantially the same as that for product sample 27-4.
The above description is only for the purpose of illustrating the present invention and is not intended to limit the present invention in any way, and the present invention is not limited to the above description, but rather should be construed as being limited to the scope of the present invention.
Claims (11)
1. A method for synthesizing an amide compound shown as a formula I is characterized by comprising the following steps: reacting the compound II, the compound III and the compound IV in a reaction system containing a catalyst to generate an amide compound shown as a formula I,
wherein the compound II is selected from one of the compounds shown in the formula II, the compound III is selected from at least one of the compounds shown in the formula III-1 and the formula III-2, the compound IV is selected from one of the compounds shown in the formula IV,
R4CN is shown in the formula IV of the formula,
wherein, R is3And R4Independently selected from C1To C20A hydrocarbon group of1To C20One of the substituted hydrocarbon groups of (1);
the compound II is one of compounds shown in a formula II-2, a formula II-4, a formula II-5, a formula II-6 and a formula II-7;
wherein m1 and m2 are independently selected from integers of 0 to 5;
m3 is selected from an integer from 0 to 7;
m4 is selected from an integer from 0 to 14;
R21、R22、R23and R24Independently selected from H, C1To C20A hydrocarbon group of1To C20One of a substituted hydrocarbyl group and a non-hydrocarbyl substituent of (a);
R5and R8Independently selected from C1To C20A hydrocarbon group of1To C20One of a substituted hydrocarbyl group and a non-hydrocarbyl substituent of (a);
the substituents in the substituted hydrocarbyl group are non-hydrocarbon substituents;
the non-hydrocarbon substituent is at least one selected from oxygen, halogen and a group having a structural formula shown in formula (2):
in the formula (2), M21Selected from hydrogen, C1To C10An alkyl group of (a);
the catalyst is selected from at least one of iron salts.
2. The method of claim 1, wherein the iron salt is selected from at least one of ferric chloride, ferrous chloride, ferric bromide, ferrous acetate, ferrous sulfate, ferrous nitrate, ferrous fluoride, ferric p-toluenesulfonate, ferrous trifluoromethanesulfonate, and ferric trifluoromethanesulfonate.
3. The method of claim 1, wherein the compound having the formula of formula III-1 is prepared from a feedstock comprising a compound having the formula of formula III-0 and hydrogen peroxide:
wherein R is3Is defined as in claim 13And (5) the consistency is achieved.
4. The method according to claim 1, wherein the molar ratio of the compound II, the compound III, the compound IV to the catalyst is as follows:
compound II: compound III: compound IV: catalyst ═ (1-2): 1: (40-90): (0.01-0.2).
5. The method according to claim 1, wherein the molar ratio of the compound II, the compound III, the compound IV to the catalyst is as follows:
compound II: compound III: compound IV: catalyst 1.5: (0.7-1.2): 77: 0.1.
6. the process according to claim 1, wherein the reaction temperature is 25 ℃ to 90 ℃ and the reaction time is 1h to 7 h.
7. The process according to claim 1, wherein the reaction temperature is 60 ℃ to 80 ℃ and the reaction time is 4h to 6 h.
8. The method according to claim 1, wherein the reaction system contains an organic solvent.
9. The method according to claim 8, wherein the organic solvent is at least one selected from the group consisting of a mixture of dioxane and acetonitrile, a mixture of dichloromethane and acetonitrile, a mixture of 1, 2-dichloroethane and acetonitrile, a mixture of carbon tetrachloride and acetonitrile, and pure acetonitrile.
10. The method according to claim 8, wherein the reaction system contains an additive selected from at least one of toluenesulfonic acid hydrate, water, sulfuric acid and trifluoromethanesulfonic acid.
11. Method according to claim 1, characterized in that it comprises at least the following steps:
reacting a compound II, a compound III, a compound IV and a solvent in a reaction system containing a catalyst containing ferric trifluoromethanesulfonate and an additive containing p-toluenesulfonic acid monohydrate at the temperature of 60-80 ℃ for 4-6 h under a stirring state, cooling to 20-30 ℃, removing the solvent through reduced pressure distillation, and performing column chromatography separation to obtain the amide compound shown in the formula I.
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Non-Patent Citations (4)
| Title |
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| Hydroalkylation of terminal aryl alkynes with alkyl diacyl peroxides;Yougui Li，第;《Tetrahedron Letters》;20161107;第57卷(第50期);第5678页Table 2、第5678页Table 1 Entry 17 * |
| Iron catalyzed methylation and ethylation of vinyl arenes;Nengbo Zhu，等;《Chemical Science》;20161202;第8卷(第3期);全文 * |
| Iron-Catalyzed C−H Alkylation of Heterocyclic C−H Bonds;Kaki Raveendra Babu，等;《ORGANIC LETTERS》;20161212;第19卷(第1期);Supporting Information第S3页第1幅图 * |
| Molecular Iodine-Mediated Difunctionalization of Alkenes with Nitriles and Thiols Leading to β-Acetamido Sulfides;Cui Huanhuan，等;《JOURNAL OF ORGANIC CHEMISTRY 》;20160229;第81卷(第6期);第2255页Table 3、第2253页Table 1 * |
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