CN109761842B - Synthesis method of alpha-F-beta-NHAc-carbonyl compound - Google Patents
Synthesis method of alpha-F-beta-NHAc-carbonyl compound Download PDFInfo
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Abstract
The invention discloses a method for synthesizing alpha-F-beta-NHAc-carbonyl compounds, which comprises the steps of dissolving unsaturated ketone compounds shown in a formula (I) and N-F reagent in acetonitrile, adding water, reacting for 12-48h at the temperature of 30-100 ℃, and after the reaction is finished, carrying out post-treatment on reaction liquid to obtain alpha-F-beta-NHAc-carbonyl compounds shown in a formula (II), wherein the reaction formula is as follows:
in the formulae (I) and (II), the substituent R1And R2Each independently selected from phenyl, thienyl, furyl or substituted phenyl; the substituent of the substituted phenyl is C1-C3 alkyl, C1-C3 alkoxy, nitro, trifluoromethyl, fluorine, chlorine or bromine; the number of the substituent groups of the substituted phenyl is 1-3. The method for synthesizing the alpha-F-beta-NHAc-carbonyl compound has the advantages of easily obtained raw materials, mild reaction conditions, no need of other catalysts, good reaction selectivity, simple and convenient operation and the like.
Description
Technical Field
The invention relates to a method for synthesizing an alpha-F-beta-NHAc-carbonyl compound.
Background
The fluorine-containing organic compound has good biological activity and stability, is widely applied to the fine chemical fields of medicines, pesticides, surfactants, fluorocarbon coatings and the like, and is deeply concerned by the medical and academic circles at home and abroad due to the huge economic value and the wide application brought by the fluorine-containing organic compound. Research shows that the fluorine-containing organic compound has good biological activity, has obvious effects on the aspects of antibiosis, anti-inflammation, anticancer and the like, and has wide application in the field of medicine. In recent years, the synthesis of α -F- β -NHAc-substituted compounds has received considerable attention and has made some progress.
Before the invention, the existing alpha-F-beta-NHAc-substituted compound synthesis method mainly comprises the following steps:
(a) synthesis of α -F- β -NHAc-substituted compounds by α -F- β -OH-substituted compounds, such as literature: tetrahedron Letters,2006,47, 6753-6756;
(b) fluorinated amidation of olefins with N-F reagents, such as the literature: chem. Commun.,2001, 233-; commu.s., 2018,54, 5907-; chem.2002,67, 6415-.
The reported alpha-F-beta-NHAc-carbonyl compounds have fewer synthesis methods, are obtained by converting other intermediate substances, and have poor stability and harsh conditions. Fluorination amidation of olefins with N-F reagents often requires additional Lewis acid catalysis. In addition, none of the existing methods directly achieve fluorinated amidation of unsaturated ketones.
The N-F reagent has the characteristics of safety, effectiveness and simple and convenient operation, avoids the defects of high toxicity, poor stability and selectivity and the like of the traditional fluorine reagent, and becomes one of the research hotspots for synthesizing fluorine-containing organic compounds in recent years. Therefore, the invention can realize the fluorinated amidation of the unsaturated ketone by using the N-F reagent, so that the reaction is simpler, more convenient, safer and more green; in addition, the invention can introduce aromatic and heterocyclic compounds on unsaturated ketone, and broadens the application range of substrates of reaction.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides a simple, convenient, efficient, safe and environment-friendly method for synthesizing the alpha-F-beta-NHAc carbonyl compound.
The synthesis method of the alpha-F-beta-NHAc-carbonyl compound shown in the formula (II) is characterized by comprising the following steps: dissolving an unsaturated ketone compound shown in a formula (I) and an N-F reagent in acetonitrile, adding water, reacting at the temperature of 30-100 ℃ for 12-48h, and after the reaction is finished, carrying out post-treatment on a reaction solution to obtain an alpha-F-beta-NHAc-carbonyl compound shown in a formula (II), wherein the reaction formula is as follows:
in the formulae (I) and (II), the substituent R1And R2Each independently selected from phenyl, thienyl, furyl or substituted phenyl; the substituent of the substituted phenyl is C1-C3 alkyl, C1-C3 alkoxy, nitro, trifluoromethyl, fluorine, chlorine or bromine; the number of the substituent groups of the substituted phenyl is 1-3.
The synthesis method of the alpha-F-beta-NHAc-carbonyl compound is characterized in that the N-F reagent is a compound shown as a formula (A), a formula (B), a formula (C) or a formula (D);
the synthesis method of the alpha-F-beta-NHAc-carbonyl compound is characterized in that the molar ratio of the unsaturated ketone compound shown in the formula (I) to the N-F reagent is 1: 1-5, and preferably 1: 1-3.
The synthesis method of the alpha-F-beta-NHAc-carbonyl compound is characterized in that the ratio of the volume of acetonitrile to the amount of the substance of the unsaturated ketone compound shown in the formula (I) is 5-25:1, preferably 7-15:1, the unit of the volume is mL, and the unit of the amount of the substance is mmol.
The synthesis method of the alpha-F-beta-NHAc-carbonyl compound is characterized in that the reaction temperature is 40-80 ℃.
The synthesis method of the alpha-F-beta-NHAc-carbonyl compound is characterized in that the reaction solution is post-treated by the following steps: adding water and an organic extracting agent into the reaction liquid for extraction, separating the liquid into an organic layer and a water layer, drying the organic layer by anhydrous sodium sulfate, removing the solvent by decompression concentration, separating the concentrated residue by column chromatography, collecting eluent containing a target product by taking a mixed solvent of petroleum ether and ethyl acetate as an eluent, and evaporating the solvent to obtain the target product, namely the alpha-F-beta-NHAc-carbonyl compound shown in the formula (II).
The synthesis method of the alpha-F-beta-NHAc-carbonyl compound is characterized in that the organic extracting agent is dichloromethane or ethyl acetate.
The synthesis method of the alpha-F-beta-NHAc-carbonyl compound is characterized in that the ratio of petroleum ether to ethyl acetate is 10-30: 1.
In the process of the present invention for preparing an α -F- β -NHAc-carbonyl compound represented by formula (II), the reaction scheme is as follows:
it can be seen that the unsaturated ketone compound shown in formula (I) reacts with the N-F reagent and acetonitrile to generate an intermediate compound containing an acetonitrile group shown in formula (III) first, and then reacts with water to perform a hydrolysis reaction to convert the acetonitrile group into an acetamido group to generate an α -F- β -NHAc-carbonyl compound shown in formula (II) (the amount of water added to the reaction system is determined by completely hydrolyzing the intermediate compound shown in formula (III) into the α -F- β -NHAc-carbonyl compound shown in formula (II), wherein only a small amount of water is required in the reaction system to complete the hydrolysis).
Compared with the prior art, the invention has the beneficial effects that:
1) the N-F reagent is used as a fluorine source and Lewis acid, and no additional catalyst is needed, so that the reaction is more green, and the cost is lower.
2) The method has the advantages of good reaction selectivity, simple and convenient operation and high product yield.
3) Realizes the fluorination amidation reaction of unsaturated ketone and enriches the synthesis method of alpha-F-beta-NHAc-carbonyl compound.
4) Acetonitrile is used as a solvent and a reactant, and other solvents are not needed, so that the reaction is more green, and the cost is lower.
In conclusion, the invention provides a synthetic method of an alpha-F-beta-NHAc-carbonyl compound catalyzed by an N-F reagent. The method has the advantages of easily available raw materials, simple and convenient operation, good substrate applicability, economy, environmental protection and the like, and is a green chemical synthesis method with better application prospect.
Detailed Description
The invention will be further described with reference to specific examples, but the scope of the invention is not limited thereto:
in the following examples, the acetonitrile added contained water.
Example 1
Chalcone (1mmol,208mg), Selectfluor (1.0mmol,247mg) were added to a 25mL single-neck reaction flask, CH was added3CN (7mL) as a solvent, and the temperature was raised to 40 ℃ to react for 12 h. After the reaction, the reaction solution was washed with water, extracted with ethyl acetate, and separated into an organic layer and an aqueous layer, and the organic layer was dried over anhydrous sodium sulfate and then concentrated by distillation under reduced pressure to remove the solvent to give a yellow oily substance. Separating the yellow oily substance by column chromatography, collecting eluent containing a target compound by using mixed liquid of petroleum ether and ethyl acetate in a volume ratio of 10:1 as eluent, evaporating the solvent, and drying to obtain 131mg of white solid 2-fluoro-3-acetamido-1, 3-diphenylpropane-1-ketone, wherein the yield is 46%, and the chemical structural formula is as follows:
characterization data:1H NMR(400MHz,CDCl3)δ7.91(d,J＝7.5Hz,2H),7.63(t,J＝7.4Hz,1H),7.50(t,J＝7.7Hz,2H),7.39(ddd,J＝12.9,10.5,7.1Hz,5H),6.65(d,J＝8.8Hz,1H),5.99(dd,J＝47.2,2.2Hz,1H),5.74(dd,J＝27.4,1.8Hz,0.46H)/5.72(dd,J＝27.6,2.0Hz,0.46H),1.96(s,3H)。13C NMR(101MHz,CDCl3)δ194.4/194.3,169.6,137.78,134.19,129.0,128.9,128.6,128.5,128.3,127.1/127.1,94.9/93.0,77.4/77.1/76.8,54.0/53.8,22.9。19F NMR(376MHz,CDCl3)δ-198.19,-202.23。HRMS:m/z Calcd for C17H16FNNaO2,[M+Na]+,308.1057；Found,308.1086。
example 2
The reaction time was prolonged to 16h, and other operating conditions were the same as in example 1, to finally obtain 114mg of white solid 2-fluoro-3-acetamido-1, 3-diphenylpropane-1-one with a yield of 40%.
Example 3
The dosage of the solvent in the system is changed into CH3CN (10mL), the other operating conditions were the same as in example 1, to finally obtain 146mg of white solid 2-fluoro-3-acetamido-1, 3-diphenylpropan-1-one with a yield of 51%.
Example 4
The amount of the fluorine reagent Selectfluor was increased to 1.2mmol (425mg), and the other operating conditions were the same as in example 1, to finally obtain 134mg of 2-fluoro-3-acetamido-1, 3-diphenylpropan-1-one as a white solid in a yield of 47%.
Example 5
The temperature of the system was raised to 60 ℃ and other operating conditions were the same as in example 1, to finally obtain 157mg of white solid 2-fluoro-3-acetamido-1, 3-diphenylpropan-1-one in 55% yield.
Example 6
1- (4-Nitrophenyl) -3-phenyl-2-propenone (1.0mmol,253mg), Selectfluor (2.0mmol,708mg) were added to a 25mL single-neck reaction flask and CH was added3CN (10mL) as a solvent, and the temperature was raised to 60 ℃ to react for 18 h. After the reaction, the reaction solution was washed with water, extracted with ethyl acetate, and separated into an organic layer and an aqueous layer, and the organic layer was dried over anhydrous sodium sulfate and then concentrated by distillation under reduced pressure to remove the solvent to give a yellow oily substance. Separating the yellow oily substance by column chromatography, taking a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 20:1 as an eluent, collecting an eluent containing a target compound, evaporating the solvent, and drying to obtain 122mg of a light yellow solid, namely 2-fluoro-3-acetamido-1- (4-nitrophenyl) -3-phenylpropan-1-one, wherein the yield is 37%, and the chemical structural formula is as follows:
characterization data:1HNMR(400MHz,CDCl3)δ8.32(d,J＝8.9Hz,2H),8.02(d,J＝8.7Hz,2H),7.45–7.33(m,5H),6.40(d,J＝8.8Hz,1H),5.92(dd,J＝47.1,2.3Hz,1H),5.73(dd,J＝26.0,2.3Hz,0.46H),5.71(dd,J＝26.2,2.3Hz,0.44H),2.03(d,J＝24.8Hz,3H)。13C NMR(101MHz,CDCl3)δ194.1/193.9,169.6,150.5,139.1,137.0,129.8/129.8,129.1,128.7,127.2,127.1,123.9,95.4/93.5,53.8/53.6,23.0/23.0。19F NMR(376MHz,CDCl3)δ-199.77,-199.79。HRMS:m/z Calcd for C17H15FN2NaO4,[M+Na]+,353.0908；Found,353.0898。
example 7
1- (4-methoxyphenyl) -3-phenyl-2-propenone (1.0mmol,253mg), Selectfluor (1.5mmol,531mg) were added to a 25mL single-neck reaction flask and CH was added3CN (10mL) as a solvent, and the temperature was raised to 70 ℃ to react for 20 h. After the reaction, the reaction solution was washed with water, extracted with ethyl acetate, and separated into an organic layer and an aqueous layer, and the organic layer was dried over anhydrous sodium sulfate and then concentrated by distillation under reduced pressure to remove the solvent to give a yellow oily substance. Separating the yellow oily substance by column chromatography, taking a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 25:1 as an eluent, collecting an eluent containing a target compound, evaporating the solvent and drying to obtain 154mg of a light yellow oily substance, namely 2-fluoro-3-acetamido-1- (4-methoxyphenyl) -3-phenylpropan-1-one, wherein the yield is 49 percent, and the chemical structural formula is as follows:
characterization data:1HNMR(400MHz,CDCl3)δ7.93(d,J＝8.7Hz,2H),7.40(dq,J＝28.0,6.9Hz,5H),6.99(d,J＝8.7Hz,2H),6.63(d,J＝8.6Hz,1H),5.96(d,J＝47.2Hz,1H),5.72(dd,J＝27.2,8.8Hz,1H),3.91(s,3H),2.00(s,3H)。13C NMR(101MHz,CDCl3)δ192.6/192.5,169.5,164.3,137.9,131.0/131.0,128.9/128.9,128.2,127.1,127.0,114.2,94.7/92.8,55.6/54.2/54.0,23.01。19F NMR(376MHz,CDCl3)δ-197.46(dd,J＝46.9,24.1Hz),-201.37(dd,J＝47.1,27.3Hz)。HRMS:m/z Calcd for C18H18FNNaO3,[M+Na]+,338.1168；Found,338.1180。
example 8
1-thienyl-3-phenyl-2-propenone (1.0mmol,214mg), Selectfluor (2.5mmol,886mg) was added to a 25mL single-neck reaction flask and CH was added3CN (12mL) as a solventHeating the mixture to 70 ℃ for reaction for 22 hours. After the reaction is finished, the reaction solution is washed by water and extracted by ethyl acetate, the liquid is separated into an organic layer and a water layer, the organic layer is dried by anhydrous sodium sulfate, and the solvent is removed by reduced pressure distillation and concentration to obtain a brown yellow oily substance. Separating the brown yellow oily substance by column chromatography, taking a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 25:1 as an eluent, collecting an eluent containing a target compound, evaporating to remove the solvent, and drying to obtain 131mg of the brown yellow oily substance 2-fluoro-3-acetamido-1-thienyl-3-phenylpropan-1-one, wherein the yield is 45%, and the chemical structural formula is as follows:
characterization data:1HNMR(400MHz,DMSO)δ8.79(d,J＝9.5Hz,1H),8.15–8.03(m,2H),7.49(d,J＝7.5Hz,2H),7.38(t,J＝7.5Hz,2H),7.30(t,J＝4.5Hz,3H),6.04(dd,J＝47.2,3.2Hz,0.80H),5.96(dd,J＝48.2,4.4Hz,0.20H),5.65(ddd,J＝30.1,9.5,2.9Hz,0.80H),5.52(ddd,J＝24.9,8.6,4.7Hz,0.20H),1.87(s,1H),1.82(s,2H)。13C NMR(101MHz,DMSO)δ187.6/187.6/187.4/187.4,169.5/169.4,140.9/140.8/137.0/136.7/136.7,138.6/138.6/135.3/135.2/135.2/135.1,129.5,128.8,128.7,128.4,128.1,127.7,96.2/95.5/94.3/93.6,55.1/54.9/54.3/54.1,22.8/22.7。19F NMR(376MHz,DMSO)δ-196.41,-198.82。HRMS:m/z Calcd for C15H14FNNaO2S,[M+Na]+,314.0621；Found,314.0625。
example 9
1- (4-trifluoromethylphenyl) -3-phenyl-2-propenone (1.0mmol,276mg), Selectfluor (1.5mmol,531mg) were added to a 25mL single-neck reaction flask and CH was added3CN (12mL) as a solvent, and the temperature was raised to 80 ℃ to react for 35 h. After the reaction, the reaction solution was washed with water, extracted with ethyl acetate, and separated into an organic layer and an aqueous layer, and the organic layer was dried over anhydrous sodium sulfate and then concentrated by distillation under reduced pressure to remove the solvent to give a yellow oily substance. Separating the yellow oily substance by column chromatography, eluting with mixed solution of petroleum ether and ethyl acetate at volume ratio of 30:1, collecting eluate containing the target compound, evaporating to remove solvent, and drying to obtain 155mg of pale yellow oily substance 2-fluoro-3-acetylAmino-1- (4-trifluoromethylphenyl) -3-phenylpropan-1-one, yield 44%, its chemical formula is:
characterization data:1HNMR(400MHz,CDCl3)δ8.00(d,J＝8.1Hz,2H),7.77(d,J＝8.1Hz,2H),7.47–7.34(m,5H),6.64(t,J＝7.0Hz,1H),5.95(dd,J＝47.2,1.6Hz,1H),5.83–5.68(m,1H),2.03(s,0.15H)/1.99(s,2.85H)。13C NMR(101MHz,CDCl3)δ194.3/194.1,169.7,137.3/137.3,135.6/134.6,135.3/135.0,129.1,128.6,127.2,126.0,125.9,124.8/122.09,95.4/93.5,53.9/53.7,23.0。19F NMR(376MHz,CDCl3)δ-63.25,-200.55(dd,J＝47.1,26.7Hz)。HRMS:m/z Calcd for C18H15F4NNaO2,[M+Na]+,276.0937；Found,276.0977。
example 10
1-phenyl-3- (4-methylphenyl) -2-propenone (1.0mmol,222mg), Selectfluor (1.5mmol,531mg) were added to a 25mL single-neck reaction flask and CH was added3CN (12mL) as a solvent, the temperature was raised to 60 ℃ to react for 38 h. After the reaction, the reaction solution was washed with water, extracted with ethyl acetate, and separated into an organic layer and an aqueous layer, and the organic layer was dried over anhydrous sodium sulfate and then concentrated by distillation under reduced pressure to remove the solvent to give a yellow oily substance. Separating the yellow oily substance by column chromatography, taking a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 30:1 as an eluent, collecting an eluent containing a target compound, evaporating the solvent and drying to obtain 159mg of a white semi-oily substance 2-fluoro-3-acetamido-1- (4-methylphenyl) -3-phenylpropan-1-one, wherein the yield is 53%, and the chemical structural formula is as follows:
characterization data:1HNMR(400MHz,CDCl3)δ7.99–7.88(m,2H),7.64(t,J＝7.4Hz,1H),7.51(t,J＝7.7Hz,2H),7.32(d,J＝8.0Hz,2H),7.21(d,J＝7.9Hz,2H),6.47(d,J＝8.0Hz,1H),5.98(dd,J＝47.2,2.1Hz,1H),5.75–5.62(m,1H),2.37(s,3H),1.97(s,3H)。13C NMR(101MHz,CDCl3)δ194.4/194.23,169.4/169.4,138.1,134.8,134.2,134.2,129.6/129.5,129.0/128.9,128.6/128.5,126.9,94.9/93.0,53.7/53.5,23.0,21.1。19F NMR(376MHz,CDCl3)δ-202.54(dd,J＝23.5,8.5Hz),-203.62(d,J＝14.4Hz)。HRMS:m/z Calcd for C18H18FNNaO2,[M+Na]+,322.1214；Found,322.1214。
example 11
1-phenyl-3- (4-methoxyphenyl) -2-propenone (1.0mmol,238mg), Selectfluor (2.0mmol,708mg) was added to a 25mL single-neck reaction flask and CH was added3CN (10mL) as a solvent was heated to 80 ℃ and reacted for 42 h. After the reaction, the reaction solution was washed with water, extracted with ethyl acetate, and separated into an organic layer and an aqueous layer, and the organic layer was dried over anhydrous sodium sulfate and then concentrated by distillation under reduced pressure to remove the solvent to give a yellow oily substance. Separating the yellow oily substance by column chromatography, taking a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 20:1 as an eluent, collecting an eluent containing a target compound, evaporating the solvent and drying to obtain 142mg of a light yellow oily substance, namely 2-fluoro-3-acetamido-1- (4-methoxyphenyl) -3-phenylpropan-1-one, wherein the yield is 45%, and the chemical structural formula is as follows:
characterization data:1H NMR(400MHz,CDCl3)δ7.92(d,J＝7.7Hz,2H),7.65(t,J＝7.3Hz,1H),7.52(t,J＝7.7Hz,2H),7.37(d,J＝8.4Hz,2H),6.96(dd,J＝20.9,8.5Hz,2H),6.58(dd,J＝36.0,8.7Hz,1H),5.97(dd,J＝47.2,2.0Hz,0.78H),5.94(dd,J＝47.2,2.0Hz,0.12H),5.68(dd,J＝26.6,9.6Hz,1H),3.91(s,0.35H)/3.83(s,2.63H),1.99(s,3H)。13C NMR(101MHz,CDCl3)δ194.6/194.4,169.5,159.5,134.4,134.3/134.2,129.9,129.1/129.0,128.6/128.6,128.4,114.3,95.0/93.1,55.4,53.5/53.3,23.0。19F NMR(376MHz,CDCl3)δ-201.37(dd,J＝47.1,27.0Hz),-201.93(dd,J＝47.2,27.2Hz)。HRMS:m/z Calcd for C18H18FNNaO3,[M+Na]+,338.1168；Found,338.1182.
example 12
1-phenyl-3- (2-chlorophenyl) -2-propenone (1.0mmol,243mg), Selectfluor (3.0mmol,1.063g), was added to a 25mL single neck reaction flask and CH was added3CN (15mL) as a solvent, and the temperature was raised to 80 ℃ to react for 16 h. After the reaction, the reaction solution was washed with water, extracted with ethyl acetate, and separated into an organic layer and an aqueous layer, and the organic layer was dried over anhydrous sodium sulfate and then concentrated by distillation under reduced pressure to remove the solvent to give a yellow oily substance. Separating the yellow oily substance by column chromatography, taking a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 20:1 as an eluent, collecting an eluent containing a target compound, evaporating to remove the solvent, and drying to obtain 99mg of the yellow oily substance 2-fluoro-3-acetamido-1- (2-chlorophenyl) -3-phenylpropan-1-one, wherein the yield is 31%, and the chemical structural formula is as follows:
characterization data:1H NMR(400MHz,CDCl3)δ8.12(dd,J＝24.9,7.6Hz,2H),7.70(t,J＝7.4Hz,1H),7.57(t,J＝7.7Hz,2H),7.48(dt,J＝8.3,5.3Hz,2H),7.34(dd,J＝9.1,5.4Hz,2H),6.92(d,J＝8.4Hz,1H),6.16(dd,J＝46.8,1.6Hz,1H),6.09(dd,J＝30.0,9.2Hz,1H),2.00(s,3H)。13C NMR(101MHz,CDCl3)δ194.0/193.8,169.6,135.0,134.6,133.7,133.2,132.2,130.1,129.8/129.4,129.1/128.7,128.5/128.4,127.3,92.8/90.9,51.8/51.6,22.7。19F NMR(376MHz,CDCl3)δ-205.53(dd,J＝46.9,30.8Hz)。HRMS:m/z Calcd for C17H15ClFNNaO2,[M+Na]+,342.0668；Found,342.0673。
example 13
1-phenyl-3- (2-bromophenyl) -2-propenone (1.0mmol,287mg), Selectfluor (1.2mmol,1.063g), was added to a 25mL single neck reaction flask and CH was added3CN (7mL) as a solvent was heated to 50 ℃ and reacted for 48 h. After the reaction, the reaction solution was washed with water, extracted with ethyl acetate, and separated into an organic layer and an aqueous layer, and the organic layer was dried over anhydrous sodium sulfate and then concentrated by distillation under reduced pressure to remove the solvent to give a pale yellow oily substance. Separating the yellowish oily substance by column chromatography with a mixture of petroleum ether and ethyl acetate at a volume ratio of 30:1As an eluent, the eluate containing the target compound was collected, the solvent was evaporated and dried to give 160mg of 2-fluoro-3-acetamido-1- (2-bromophenyl) -3-phenylpropan-1-one as a pale yellow oil in 44% yield, which has the chemical formula:
characterization data:1HNMR(400MHz,CDCl3)δ8.12(d,J＝7.6Hz,2H),7.69(dd,J＝16.9,7.9Hz,2H),7.57(t,J＝7.7Hz,2H),7.45(d,J＝7.7Hz,1H),7.39(t,J＝7.5Hz,1H),7.25(t,J＝7.1Hz,1H),6.78(d,J＝8.1Hz,1H),6.23–5.97(m,2H),1.99(s,3H)。13C NMR(101MHz,CDCl3)δ193.9/193.7,169.3,136.6,134.5,133.8,133.8,133.2,129.7,129.0,128.6,127.8,122.6,92.6/90.7,54.0/53.8,22.8。19F NMR(376MHz,CDCl3)δ-204.86(dd,J＝46.4,27.5Hz),-205.73(dd,J＝46.9,30.7Hz)。HRMS:m/z Calcd for C17H15BrFNNaO2,[M+Na]+,386.0162；Found,386.0196。
example 14
1-phenyl-3- (4-bromophenyl) -2-propenone (1.0mmol,287mg), Selectfluor (1.2mmol,1.063g), was added to a 25mL single neck reaction flask and CH was added3CN (15mL) as a solvent, and the temperature was raised to 50 ℃ to react for 22 h. After the reaction, the reaction solution was washed with water, extracted with ethyl acetate, and separated into an organic layer and an aqueous layer, and the organic layer was dried over anhydrous sodium sulfate and then concentrated by distillation under reduced pressure to remove the solvent to give a pale yellow oily substance. Separating the light yellow oily substance by column chromatography, taking a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 30:1 as an eluent, collecting an eluent containing a target compound, evaporating the solvent and drying to obtain 153mg of the light yellow oily substance 2-fluoro-3-acetamido-1- (4-bromophenyl) -3-phenylpropan-1-one, wherein the yield is 42%, and the chemical structural formula is as follows:
characterization data:1H NMR(400MHz,CDCl3)δ7.91(d,J＝7.1Hz,2H),7.67(t,J＝6.6Hz,1H),7.53(d,J＝4.1Hz,4H),7.32(d,J＝8.0Hz,2H),6.65(d,J＝7.3Hz,1H),5.95(d,J＝47.1Hz,1H),5.69(dd,J＝27.0,7.9Hz,1H),1.99(s,3H)。13C NMR(101MHz,CDCl3)δ194.3/194.1,169.6,136.8,134.3,134.1,132.0,129.0,128.9,128.6/128.6,122.3,94.6/92.7,53.5//53.3,23.0。19F NMR(376MHz,CDCl3)δ-197.72(dd,J＝47.2,25.4Hz),-201.47(dd,J＝46.8,27.2Hz)。HRMS:m/z Calcd for C17H15BrFNNaO2,[M+Na]+,386.0162；Found,386.0199。
example 15
1-phenyl-3- (4-fluorophenyl) -2-propenone (1.0mmol,226mg), Selectfluor (2.5mmol,886mg) was added to a 25mL single-neck reaction flask and CH was added3CN (12mL) as a solvent, and the temperature was raised to 70 ℃ to react for 48 h. After the reaction, the reaction solution was washed with water, extracted with ethyl acetate, and separated into an organic layer and an aqueous layer, and the organic layer was dried over anhydrous sodium sulfate and then concentrated by distillation under reduced pressure to remove the solvent to give a yellow oily substance. Separating the yellow oily substance by column chromatography, taking a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 30:1 as an eluent, collecting an eluent containing the target compound, evaporating the solvent and drying to obtain 112mg of a white semisolid oily substance 2-fluoro-3-acetamido-1- (4-fluorophenyl) -3-phenylpropan-1-one, wherein the yield is 37%, and the chemical structural formula is as follows:
characterization data:1H NMR(400MHz,CDCl3)δ7.91(d,J＝7.7Hz,2H),7.66(t,J＝7.4Hz,1H),7.53(t,J＝7.7Hz,2H),7.43(dd,J＝8.0,5.4Hz,2H),7.09(t,J＝8.5Hz,2H),6.68(d,J＝8.6Hz,1H),5.96(dd,J＝47.1,1.9Hz,1H),5.72(dd,J＝26.7,8.2Hz,1H),1.99(s,3H)。13C NMR(101MHz,CDCl3)δ194.4/194.2,169.6,163.7/161.3,134.3,134.1,133.6,133.6,129.0/129.0/128.9,128.6/128.5,115.9/115.7,94.8/92.9,53.4/53.2,22.9。19F NMR(376MHz,CDCl3)δ-112.50--117.46(m),-201.44(dd,J＝47.1,27.2Hz)。HRMS:m/z Calcd for C17H15F2NNaO2,[M+Na]+,326.0969；Found,326.0986。
example 16
1-phenyl-3- (3-methylphenyl) -2-propenone (1.0mmol,222mg), Selectfluor (1.5mmol,531mg) were added to a 25mL single-neck reaction flask and CH was added3CN (15mL) as a solvent, the temperature was raised to 60 ℃ to react for 44 h. After the reaction, the reaction solution was washed with water, extracted with ethyl acetate, and separated into an organic layer and an aqueous layer, and the organic layer was dried over anhydrous sodium sulfate and then concentrated by distillation under reduced pressure to remove the solvent to give a yellow oily substance. Separating the yellow oily substance by column chromatography, taking a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 20:1 as an eluent, collecting an eluent containing the target compound, evaporating the solvent and drying to obtain 129mg of brown oily substance 2-fluoro-3-acetamido-1- (3-methylphenyl) -3-phenylpropan-1-one, wherein the yield is 43%, and the chemical structural formula is as follows:
characterization data:1HNMR(400MHz,DMSO)δ8.70(d,J＝9.5Hz,1H),7.95(d,J＝7.6Hz,2H),7.68(t,J＝7.3Hz,1H),7.56(t,J＝7.6Hz,2H),7.30(s,1H),7.26(d,J＝4.7Hz,2H),7.11(d,J＝3.9Hz,1H),6.34(dd,J＝46.5,2.3Hz,1H),5.55(dd,J＝31.1,9.5Hz,1H),2.32(s,3H),1.80(s,3H)。13C NMR(101MHz,CDCl3)δ199.7/199.5,174.0,143.6,142.7,139.6,138.9,134.0,133.6,133.5,133.3,133.0,129.5,100.5/98.6,58.4/58.2,27.4,26.3。19F NMR(376MHz,DMSO)δ-198.93(dd,J＝47.8,24.9Hz),-202.42(dd,J＝46.4,31.2Hz)。HRMS:m/z Calcd for C36H37F2N2O4,[2M+H]+,599.2716；Found,599.2741。
Claims (7)
1. as shown in formula (II)α-F-β-NHAc-carbonyl compound, characterized in that the synthesis method is: dissolving unsaturated ketone compound shown in formula (I) and N-F reagent in acetonitrile, adding water, reacting at 30-100 deg.C for 12-48h, and post-treating reaction solution to obtain compound shown in formula (II)α-F-β-NHAc-carbonyl compound of the formula:
in the formulae (I) and (II), the substituent R1And R2Each independently selected from phenyl, thienyl, furyl or substituted phenyl; the substituent of the substituted phenyl is C1-C3 alkyl, C1-C3 alkoxy, nitro, trifluoromethyl, fluorine, chlorine or bromine; the number of the substituent groups of the substituted phenyl is 1-3;
the N-F reagent is a compound shown as a formula (A);
the molar ratio of the unsaturated ketone compound shown in the formula (I) to the N-F reagent is 1: 1-3.
2. The method of claim 1α-F-β-NHAc-carbonyl compound synthesis method, characterized in that the volume of acetonitrile and the unsaturated ketone compound shown in formula (I) substance amount ratio is 5-25:1, the volume unit is mL, the substance amount unit is mmol.
3. The method of claim 2α-F-β-NHAc-carbonyl compound synthesis method, characterized in that the volume of acetonitrile and the unsaturated ketone compound shown in formula (I) substance amount ratio is 7-15:1, the volume unit is mL, the substance amount unit is mmol.
4. The method of claim 1α-F-β-NHAc-carbonyl compound synthesis method, characterized in that the reaction temperature is 40-80 ℃.
5. The method of claim 1α-F-β-NHAc-carbonyl compound synthesis method, characterized in that the reaction solution after treatment steps: adding water and organic matter into the reaction liquidExtracting with extractant to obtain organic layer and water layer, drying the organic layer with anhydrous sodium sulfate, concentrating under reduced pressure to remove solvent, separating the concentrated residue by column chromatography, eluting with mixed solvent of petroleum ether and ethyl acetate, collecting eluate containing target product, and evaporating to remove solvent to obtain target product represented by formula (II)α-F-β-NHAc-carbonyl compound.
6. The method of claim 5α-F-β-NHAc-carbonyl compound synthesis method, characterized in that the organic extractant is dichloromethane or ethyl acetate.
7. The method of claim 5α-F-βThe method for synthesizing the-NHAc-carbonyl compound is characterized in that the ratio of the petroleum ether to the ethyl acetate is 10-30: 1.
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