CN103467323B - Method for preparing beta-unsaturated enamine ester derivative - Google Patents
Method for preparing beta-unsaturated enamine ester derivative Download PDFInfo
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Abstract
The invention discloses a method for preparing a beta-unsaturated enamine ester derivative. The method specifically comprises the following steps: in the presence of alkali, preparing beta-unsaturated enamine ester derivative through multi-component free radical coupling reaction in water or an organic solvent by using styrene derivative, amine derivative and ethyl bromodifluoroacetate as reactant, using cobalt-containing compound as a catalyst, tertiary butanol hydrogen peroxide as oxidant. According to the invention, the ethyl bromodifluoroacetate is used for preparing the beta-unsaturated enamine ester derivative for the first time, and the de-fluoridation reaction condition of the product is mild; the preparation method disclosed by the invention, the raw materials are simple and available, the catalyst dosage is less, the reaction process is simple and controllable, the reaction condition is mild, and the preparation method is suitable for industrial application.
Description
Technical field
The invention belongs to the preparing technical field of ester class organic compound, be specifically related to the catalysis preparation method of a kind of β-unsaturated enamine ester derivative.
Background technology
β-unsaturated enamine ester derivative is the very important structural unit of a class, is extensively present in and has among the natural product of physiology pharmaceutical activity, drug molecule, and be also very important organic synthesis intermediate.The synthetic concern that obtains many investigators of β-unsaturated enamine ester derivative.
The use monobromo-acetic acid esters such as Veronese and cyano group compounds generation cloth Levin Si reaction prepared β-unsaturated enamine ester derivative (referring to Morelli, C. F.; Monica, M.; Veronese, A. C. Tetrahedron 1999,55,10803); The people such as Grabowski have reported and have used Pyruvic Acid Methyl ester and Pyrrolidine oxalyl chloride methyl esters as reactant, at the B less to environmental influence (OMe)
3under catalysis, an one-pot three-step has been prepared the method for β-unsaturated enamine ester compound (referring to Cvetovich, R. J.; Pipik, B.; Hartner, F. W.; Grabowski, E. J. J. Tetrahedron Lett. 2003,44,5867); The people such as Batra have reported that the method for preparing β-unsaturated enamine ester derivative after a kind of Lei Ni of use-nickel hydrogenation catalyst reduction isoxazole class derivative is (referring to Singh, V.; Saxena, R.; Batra, S. J. Org. Chem. 2004,70,353); Although above method can be prepared product, have that catalyst levels is large, a shortcoming of expensive raw material price, severe reaction conditions, long reaction time.
After using electron-deficient terminal alkyne and aromatic aldehyde compounds to be coupled, addition makes β-unsaturated enamine ester derivative to the people such as Maas with secondary amine again; But this reaction has been used a large amount of butyl lithium catalysts to cause post-processing difficulty to increase, and reaction to start temperature be-100 ℃, reaction conditions is strict; Two large drawbacks limit that this synthetic method has its industrial applications (referring to Maas, G.; Nikolai, J. Synthesis 2003,2679); The people such as Kim have reported that tertiary amine and propiolate can react under the effect of zinc bromide and have obtained β-unsaturated enamine ester cpds; But the amount of the catalyzer that the method relates to need to be worked as magnitude, this is large and be difficult to industrialization (referring to Lee, K. Y. to environmental influence; Lee, C. G.; Na, J. E.; Kim, J. N. Tetrahedron Lett. 2005,46,69); The people such as Nielsen have reported a kind of Yin Lebu amine and the method for the synthetic β-unsaturated enamine ester cpds of alkynes sodium reaction Wei that utilizes; But Wei, the kind of Yin Lebu amine had a great impact for the structure of product; Cause the method substrate narrow application range (referring to Persson, T.; Nielsen, J. Org. Lett. 2006,8,3219).
Therefore find that a kind of raw material sources are simple, low cost, high-level efficiency, substrate scope preparation method wide, easy and simple to handle be necessary effectively to synthesize β-unsaturated enamine ester derivative.
In addition Bromodifluoroacetic acid ethyl ester can be applicable to organic synthesis field as fluorine-containing synthon, but has no its report aspect preparation β-unsaturated enamine ester derivative; And the going to fluoridize of the product being prepared by fluorine-containing synthon in prior art needs exacting terms; such as Cao; s. wait people to use lithium aluminum hydride to make reductive agent; with tetrahydrofuran (THF), make solvent; the product that reaction can obtain fluoridizing under the condition of 0 ℃; but the condition of this reaction needed anhydrous and oxygen-free, in suitability for industrialized production, be very restricted (referring to: Wu, J.-J.; Cheng, J.-H.; Zhang, J.; Shen, L.; Qian, X.-H.; Cao, S. Tetrahedron 2011,67,285.).
Summary of the invention
The object of this invention is to provide a kind of raw material sources preparation method simple, easy and simple to handle, to prepare simply, safely, environmentally-friendly β-unsaturated enamine ester derivative.
To achieve the above object of the invention, the technical solution used in the present invention is:
A kind of method of preparing β-unsaturated enamine ester derivative, comprise the following steps: under the existence of alkali, take styrene derivatives, amine and Bromodifluoroacetic acid ethyl ester is reactant, take cobalt compound as catalyzer, take trimethyl carbinol hydrogen peroxide as oxygenant, in water or organic solvent, by three component free radical cross-coupling reactions, obtain product β-unsaturated enamine ester;
The structural formula of described styrene derivatives is:
in formula, Ar is selected from: a kind of in the 4-aminophenyl of phenyl, 4-tert-butyl-phenyl, 4-p-methoxy-phenyl, 4-cyano-phenyl, 4-aminomethyl phenyl, 4-bromophenyl, 4-chloro-phenyl-, 3-bromophenyl, naphthyl, 4-fluorophenyl, 3-fluorophenyl, 3-trifluoromethyl and tertiary butyl oxycarbonyl protection;
Described amine is selected from: a kind of in triethylamine, tripropyl amine, Tributylamine, triisobutyl amine, dipropyl amine, dibutylamine, dihexylamine;
Described cobalt compound is selected from: acetylacetone cobalt (II), acetylacetone cobalt (III), cobaltous fluoride (II), cobaltous fluoride (III), four hydration cobaltous acetates (II), Cobaltous nitrate hexahydrate (II), six hydration fluoroboric acid cobalts (II), cobalt (III) potassium cyanide, cobaltous phosphate (II), Cobalt monosulfate heptahydrate (II), cobaltous iodide (II), Hexammine cobaltic chloride (III), six Jing Ti/Bao Pian COBALT NITRATE CRYSTALS/FLAKESs (III) sodium, cobaltous thiocyanate (II), cobalt stearate (II), two (diphenylphosphine) ethane chlorination cobalt (II), [1,1 '-bis-(diphenylphosphine) ferrocene] a kind of in cobalt dichloride (II),
Described alkali is selected from: cesium carbonate, salt of wormwood, cesium acetate, sodium hydroxide, three hypophosphite monohydrate potassium, triethylene diamine, 2, a kind of in 6-lutidine.
In technique scheme, described organic solvent is benzene, DMF, toluene, acetonitrile, 1,2-ethylene dichloride, 1，1，1-trichloroethane or tetrahydrofuran (THF); Be preferably benzene.
In technique scheme, catalyzer is preferably acetylacetone cobalt (II); Alkali is preferably cesium carbonate.
In technique scheme, according to molar ratio computing, 5～40 % that the consumption of catalyzer is styrene derivatives; Be preferably 20 %.
In technique scheme, according to molar ratio computing, the consumption of alkali is styrene derivatives 2～6 times; Be preferably 3 times.
In technique scheme, according to molar ratio computing, the consumption of Bromodifluoroacetic acid ethyl ester is styrene derivatives 2～5 times; The consumption of amine is 3～10 times of styrene derivatives; The consumption of oxygenant is 1～10 times of styrene derivatives; Preferably, according to molar ratio computing, the consumption of Bromodifluoroacetic acid ethyl ester is styrene derivatives 3 times; The consumption of amine is 5 times of styrene derivatives; The consumption of oxygenant is 6 times of styrene derivatives.
In technique scheme, the temperature of reaction of described three component free radical cross-coupling reactions is 60～100 ℃; Reaction times is 12～24 hours; Preferably, temperature of reaction is 80 ℃, and the reaction times is 12 hours.
After the present invention has reacted, carry out purification processes, belong to prior art, those skilled in the art can select suitable reagent according to the character of final product.The present invention is preferably: reacted rear first with saturated sodium sulfite cancellation reaction, then with ethyl acetate or dichloromethane extraction, recycle silicon glue adsorbs vacuum and is spin-dried for solvent, then uses the mixed solvent of ethyl acetate/petroleum ether (volume ratio is 1: 10) to carry out simple column chromatography and just can obtain final product.
The invention also discloses the application of Bromodifluoroacetic acid ethyl ester in preparation β-unsaturated enamine ester derivative.
The structural formula of described Bromodifluoroacetic acid ethyl ester is:
。
Because technique scheme is used, the present invention compared with prior art has following advantages:
1. the present invention uses cobalt compound cheap and easy to get to prepare β-unsaturated enamine ester derivative as catalyst, and reactive behavior is high, and the reaction times is short, and the aftertreatment of reaction is simple, is conducive to the purifying of product;
The present invention first by Bromodifluoroacetic acid ethyl ester, styrene derivatives, sulfonamide derivatives as reactant, by polycomponent one kettle way, directly make β-unsaturated enamine ester derivative; And under gentle reaction conditions, product can complete to be fluoridized;
3. preparation method disclosed by the invention has universality to multiple reaction substrate, and raw material sources are simple, is easy to obtain, and cost is low, easy and simple to handle, and preparation process environmental protection is conducive to the suitability for industrialized production of β-unsaturated enamine ester.
Embodiment
Below in conjunction with embodiment, the invention will be further described:
Embodiment mono-:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), N, dinethylformamide 8 mL, triethylamine 3 a (10 mmol), trimethyl carbinol hydrogen peroxide TBHP(12 mmol), then this system heats after approximately 12 hours in air under 80 ℃ of conditions, saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 60 %.
Product is analyzed, and result is as follows:
1h NMR (400 MHz, CDCl
3) δ 7.73 (d,
j=7.6 Hz, 2H), 7.32 (d,
j=7.6 Hz, 2H), 5.65 (s, 1H), 4.39 (q,
j=6.9 Hz, 2H), 3.21 (q,
j=6.7 Hz, 4H), 1.30 (t,
j=6.8 Hz, 3H), 1.23 (s, 9H), 1.15 (t,
j=6.9 Hz, 6H).
13C NMR (100 MHz, CDCl 3 ) δ 185.9,165.5,153.94,153.91,136.8,126.8,124.5,89.8,61.4,44.7,34.3,30.7,13.4,12.0.hRMS For C
20h
30nO
3: 332.2226, Found:332.2209 (M+1)
+. IR (KBr, cm
-1): ν 2966,2938, and 1737,1630,1606,1562,1533,1470,1447,1383,1359. above digital proof gained compounds are object product.
Embodiment bis-:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), toluene 8 mL, triethylamine 3 a (10 mmol), trimethyl carbinol hydrogen peroxide TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 75 %.
Embodiment tri-:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), acetonitrile 8 mL, triethylamine 3 a (10 mmol), trimethyl carbinol hydrogen peroxide TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 62 %.
Embodiment tetra-:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), 1,2-ethylene dichloride 8 mL, triethylamine 3 a (10 mmol), trimethyl carbinol hydrogen peroxide TBHP(12 mmol), then this system heats after approximately 12 hours in air under 80 ℃ of conditions, saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 70 %.
Embodiment five:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), 1,1,1-trichloroethane, 8 mL, triethylamine 3 a (10 mmol), trimethyl carbinol hydrogen peroxide TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 76 %.
Embodiment six:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), tetrahydrofuran (THF) 8 mL, triethylamine 3 a (10 mmol), trimethyl carbinol hydrogen peroxide TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 37 %.
Embodiment seven:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.1 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), trimethyl carbinol hydrogen peroxide TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 65 %.
Embodiment eight:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.2 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), trimethyl carbinol hydrogen peroxide TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 77 %.
Embodiment nine:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.3 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), trimethyl carbinol hydrogen peroxide TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 83 %.
Embodiment ten:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.5 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), trimethyl carbinol hydrogen peroxide TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 92 %.
Embodiment 11:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.6 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), trimethyl carbinol hydrogen peroxide TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 91 %.
Embodiment 12:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.7 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), trimethyl carbinol hydrogen peroxide TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 91 %.
Embodiment 13:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.8 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), trimethyl carbinol hydrogen peroxide TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 92 %.
Embodiment 14:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (6 mmol), trimethyl carbinol hydrogen peroxide TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 45 %.
Embodiment 15:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (8 mmol), trimethyl carbinol hydrogen peroxide TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 72 %.
Embodiment 16:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (12 mmol), trimethyl carbinol hydrogen peroxide TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 85 %.
Embodiment 17:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (16 mmol), trimethyl carbinol hydrogen peroxide TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 80 %.
Embodiment 18:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (20 mmol), trimethyl carbinol hydrogen peroxide TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 75 %.
Embodiment 19:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (4 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), trimethyl carbinol hydrogen peroxide TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 70 %.
Embodiment 20:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (8 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), trimethyl carbinol hydrogen peroxide TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 85 %.
Embodiment 21:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (10 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), trimethyl carbinol hydrogen peroxide TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 75 %.
Embodiment 22:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), trimethyl carbinol hydrogen peroxide TBHP(2 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 20 %.
Embodiment 23:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), trimethyl carbinol hydrogen peroxide TBHP(6 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 47 %.
Embodiment 24:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), trimethyl carbinol hydrogen peroxide TBHP(10 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 76 %.
Embodiment 25:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), trimethyl carbinol hydrogen peroxide TBHP(16 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 65 %.
Embodiment 26:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), trimethyl carbinol hydrogen peroxide TBHP(20 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 55 %.
Embodiment 27:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), trimethyl carbinol hydrogen peroxide TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 18 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 92 %.
Embodiment 28:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), trimethyl carbinol hydrogen peroxide TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 24 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 85 %.
Embodiment 29:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), trimethyl carbinol hydrogen peroxide TBHP(12 mmol), then this system heated under 60 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 75 %.
Embodiment 30:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), trimethyl carbinol hydrogen peroxide TBHP(12 mmol), then this system heated under 70 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 82 %.
Embodiment 31:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), trimethyl carbinol hydrogen peroxide TBHP(12 mmol), then this system heated under 90 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 85 %.
Embodiment 32:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), trimethyl carbinol hydrogen peroxide TBHP(12 mmol), then this system heated under 100 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 87 %.
Embodiment 33:
In reaction flask, pack successively acetylacetone cobalt (II) Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), trimethyl carbinol hydrogen peroxide TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 a, yield is 93 %.
Embodiment 34:
In reaction flask, pack successively Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 b(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 b, yield is 66 %.
Product is analyzed, and result is as follows:
1h NMR (400 MHz, CDCl
3) δ 7.90 – 7.84 (m, 2H), 7.49 – 7.33 (m, 3H), 5.74 (s, 1H), 4.50 (q,
j=6.9 Hz, 2H), 3.33 (q,
j=7.0 Hz, 4H), 1.41 (t,
j=7.0 Hz, 3H), 1.27 (t,
j=6.8 Hz, 6H).
13c NMR (100 MHz, CDCl
3) δ 186.2,165.4,154.3,139.6,130.7,127.7,127.0,89.8,61.6,44.8,13.5,12.4.HRMS For C
16h
22nO
3: 276.1600, Found 276.1602 (M+1)
+. IR (KBr, cm
-1): ν 2980,2936, and 1734,1632,1597,1577,1531,1472,1445,1398,1383,1358. above digital proof gained compounds are object product.
Embodiment 35:
In reaction flask, pack successively Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 c(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 c, yield is 62 %.
Product is analyzed, and result is as follows:
1h NMR (400 MHz, CDCl
3) δ 7.69 (d,
j=7.2 Hz, 2H), 7.10 (d,
j=7.5 Hz, 2H), 5.65 (s, 1H), 4.40 (q,
j=6.7 Hz, 2H), 3.22 (q,
j=6.6 Hz, 4H), 2.28 (s, 3H), 1.31 (t,
j=7.1 Hz, 3H), 1.16 (t,
j=6.8 Hz, 6H).
13C NMR (100 MHz, CDCl 3 ) δ 186.0,165.6,154.1,141.1,136.9,128.4,127.1,89.8,61.6,44.8,21.0,13.5,12.1.hRMS For C
17h
24nO
3: 290.1756, Found:290.1725 (M+1)
+. IR (KBr, cm
-1): ν 2979,2935, and 1736,1630,1607,1568,1531,1470,1446,1383,1358. above digital proof gained compounds are object product.
Embodiment 36:
In reaction flask, pack successively Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmolL), TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 d, yield is 60 %.
Product is analyzed, and result is as follows:
1h NMR (400 MHz, CDCl
3) δ 7.66 (d,
j=8.1 Hz, 2H), 7.44 (d,
j=8.2 Hz, 2H), 5.59 (s, 1H), 4.40 (q,
j=6.7 Hz, 2H), 3.25 (q,
j=6.7 Hz, 4H), 1.33 (t,
j=7.1 Hz, 3H), 1.19 (t,
j=6.7 Hz, 6H).
13C NMR (100 MHz, CDCl 3 ) δ 185.0,165.4,154.8,138.6,130.9,128.7,125.3,89.3,61.8,45.0,13.5,12.5.hRMS For C
16h
20 79brNO
3: 354.0705, C
16h
20 81brNO
3: 356.0705, Found:354.0714 (
79br), 356.0699 (
81br). IR (KBr, cm
-1): ν 2979,2937, and 1735,1630,1585,1527,1469,1446,1403,1384,1357. above digital proof gained compounds are object product.
Embodiment 37:
In reaction flask, pack successively Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 e(2 mmol), compound 2 a(6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 e, yield is 75 %.
Product is analyzed, and result is as follows:
1h NMR (400 MHz, CDCl
3) δ 7.73 (d,
j=8.0 Hz, 2H), 7.27 (d,
j=8.1 Hz, 2H), 5.59 (s, 1H), 4.40 (q,
j=7.0 Hz, 2H), 3.24 (q,
j=7.7 Hz, 4H), 1.32 (t,
j=7.2 Hz, 3H), 1.17 (t,
j=7.0 Hz, 6H).
13C NMR (100 MHz, CDCl 3 ) δ 184.8,165.4,154.7,138.1,136.7,128.5,127.9,89.4,61.8,44.9,13.5,12.1.hRMS For C
16h
20 35clNO
3: 310.1210, C
16h
20 37clNO
3: 312.1210, Found:310.1217 (
35cl), 312.1200 (
37cl). IR (KBr, cm
-1): ν 2980,2936, and 1735,1629,1589,1569,1528,1468,1447,1383,1357. above digital proof gained compounds are object product.
Embodiment 38:
In reaction flask, pack successively Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 f(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 f, yield is 80 %.
Product is analyzed, and result is as follows:
1h NMR (400 MHz, CDCl
3) δ 7.93 (d,
j=7.4 Hz, 2H), 7.69 (d,
j=6.8 Hz, 2H), 5.66 (s, 1H), 4.50 (q,
j=5.9 Hz, 2H), 3.35 (q,
j=6.7 Hz, 4H), 1.41 (t,
j=6.3 Hz, 3H), 1.29 (t,
j=6.1 Hz, 6H).
13C NMR (100 MHz, CDCl 3 ) δ 184.1,165.0,155.3,143.4,131.6,127.5,118.0,113.6,89.2,61.8,45.7,13.4,10.8.hRMS For C
17h
21n
2o
3: 301.1552, Found:301.1548 (M+1)
+. IR (KBr, cm
-1): ν 2976,2934, and 2228,1736,1626,1527,1469,1450,1384,1357. above digital proof gained compounds are object product.
Embodiment 39:
In reaction flask, pack successively Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 g(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 g, yield is 70 %.
Product is analyzed, and result is as follows:
1h NMR (400 MHz, CDCl
3) δ 8.00 (s, 1H), 7.90 – 7.68 (m, 1H), 7.66 – 7.45 (m, 1H), 7.42 – 7.16 (m, 1H), 5.57 (s, 1H), 4.41 (q,
j=6.7 Hz, 2H), 3.26 (q,
j=6.7 Hz, 4H), 1.33 (t,
j=7.1 Hz, 3H), 1.20 (t,
j=7.0 Hz, 6H).
13c NMR (100 MHz, CDCl
3) δ 184.5,165.3,154.9,141.7,133.5,130.1,129.4,125.6,122.0,89.3,61.8,45.0,13.5,12.1. HRMS For C
16h
20 79brNO
3: 354.0705, C
16h
20 81brNO
3: 356.0705. Found:354.0707 (
79br), 356.0696 (
81br). IR (KBr, cm
-1): ν 2980,2937, and 1736,1629,1531,1467,1447,1382,1357. above digital proof gained compounds are object product.
Embodiment 40:
In reaction flask, pack successively Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 h(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 h, yield is 72 %.
Product is analyzed, and result is as follows:
1h NMR (400 MHz, CDCl
3) δ 8.29 (s, 1H), 7.93 – 7.69 (m, 4H), 7.47 – 7.33 (m, 2H), 5.79 (s, 1H), 4.43 (q,
j=6.6 Hz, 2H), 3.24 (q,
j=6.6 Hz, 4H), 1.33 (t,
j=7.1 Hz, 3H), 1.17 (t,
j=6.8 Hz, 6H).
13c NMR (100 MHz, CDCl
3) δ 186.2,165.6,154.5,137.0,134.3,132.3,128.8,127.6,127.5,127.3,127.0,126.0,124.1,90.0,61.8,45.0,13.6,12.5. HRMS For C
20h
24nO
3: 326.1756, Found:326.1772 (M+1)
+. IR (KBr, cm
-1): ν 2978,2929, and 1733,1628,1528,1467,1412,1384,1357. above digital proof gained compounds are object product.
Embodiment 41:
In reaction flask, pack successively Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 i(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 i, yield is 75 %.
Product is analyzed, and result is as follows:
1h NMR (400 MHz, CDCl
3) δ 7.85 – 7.74 (m, 2H), 7.02 – 6.91 (m, 2H), 5.60 (s, 1H), 4.41 (q,
j=7.0 Hz, 2H), 3.24 (q,
j=6.6 Hz, 4H), 1.32 (t,
j=7.1 Hz, 3H), 1.18 (t,
j=7.0 Hz, 6H).
13c NMR (100 MHz, CDCl
3) δ 184.8,165.44,165.36,162.8,154.5,135.94,135.91,129.44,129.35,114.7,114.5,89.4,61.7,45.1,13.8,13.5. HRMS For C
16h
21fNO
3: 294.1505, Found:294.1516 (M+1)
+. IR (KBr, cm
-1): ν 2981,2937, and 1736,1631,1597,1531,1470,1383,1358. above digital proof gained compounds are object product.
Embodiment 42:
In reaction flask, pack successively Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 j(2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 j, yield is 77 %.
Product is analyzed, and result is as follows:
1h NMR (400 MHz, CDCl
3) δ 7.59 – 7.51 (m, 1H), 7.52 – 7.43 (m, 1H), 7.33 – 7.22 (m, 1H), 7.11 – 7.00 (m, 1H), 5.59 (s, 1H), 4.40 (q,
j=7.1 Hz, 2H), 3.24 (q,
j=6.6 Hz, 4H), 1.32 (t,
j=7.1 Hz, 3H), 1.18 (t,
j=7.0 Hz, 6H).
13c NMR (100 MHz, CDCl
3) δ 184.5,165.2,163.4,161.0,154.8,142.03,141.97,129.3,129.2,122.63,122.61,117.5,117.3,113.9,113.7,89.3,61.7,44.8,13.4,10.8. HRMS For C
16h
21fNO
3: 294.1505, Found:294.1518 (M+1)
+. IR (KBr, cm
-1): ν 2981,2937, and 1737,1632,1583,1531,1470,1383,1357. above digital proof gained compounds are object product.
Embodiment 43:
In reaction flask, pack successively Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 k (2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 k, yield is 95 %.
Product is analyzed, and result is as follows:
1h NMR (400 MHz, CDCl
3) δ 8.08 – 8.03 (m, 1H), 7.98 – 7.89 (m, 1H), 7.64 – 7.54 (m, 1H), 7.49 – 7.37 (m, 1H), 5.61 (s, 1H), 4.40 (q,
j=7.1 Hz, 2H), 3.25 (q,
j=6.6 Hz, 4H), 1.31 (t,
j=7.2 Hz, 3H), 1.17 (t,
j=7.1 Hz, 6H).
13c NMR (100 MHz, CDCl
3) δ 184.2,165.0,155.0,140.2,130.3,130.1,129.7,129.4,128.2,126.8,124.8,123.7,123.6,122.1,88.8,61.6,45.4,13.2,10.6. HRMS For C
17h
21f
3nO
3: 344.1474, Found:344.1469 (M+1)
+. IR (KBr, cm
-1): ν 2982,2940, and 1737,1632,1605,1589,1531,1470,1383,1358. above digital proof gained compounds are object product.
Embodiment 44:
In reaction flask, pack successively Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 l (2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 l, yield is 70 %.
Product is analyzed, and result is as follows:
1h NMR (400 MHz, CDCl
3) δ 7.82 (d,
j=8.4 Hz, 2H), 7.44 (d,
j=8.3 Hz, 2H), 7.33 (s, 1H), 5.71 (s, 1H), 4.46 (q,
j=7.0 Hz, 2H), 3.30 (q,
j=6.7 Hz, 4H), 1.48 (s, 9H), 1.38 (t,
j=7.1 Hz, 3H), 1.24 (t,
j=6.9 Hz, 6H).
13c NMR (100 MHz, CDCl
3) δ 185.2,165.7,153.9,152.4,141.7,133.5,128.1,117.0,89.6,79.8,61.5,44.7,27.9,13.5,12.3. HRMS For C
21h
31n
2o
5: 391.2233, Found:391.2226 (M+1)
+. IR (KBr, cm
-1): ν 2980,2941, and 1730,1667,1627,1602,1584,1526,1470,1412,1385,1358. above digital proof gained compounds are object product.
Embodiment 45:
in reaction flask, pack successively Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 m (2 mmol), compound 2 a (6 mmol), benzene 8 mL, triethylamine 3 a (10 mmol), TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 4 m, yield is 68 %.
Product is analyzed, and result is as follows:
1h NMR (400 MHz, CDCl
3) δ 7.78 (d,
j=8.4 Hz, 2H), 6.81 (d,
j=8.5 Hz, 2H), 5.64 (s, 1H), 4.41 (q,
j=6.9 Hz, 2H), 3.76 (s, 3H), 3.24 (q,
j=6.9 Hz, 4H), 1.33 (t,
j=7.1 Hz, 3H), 1.18 (t,
j=6.8 Hz, 6H).
13c NMR (100 MHz, CDCl
3) δ 185.8,166.1,162.0,154.2,132.7,129.4,113.2,90.1,62.0,55.3,13.9. MS For C
17h
24nO
4: 306, Found:306 (M+1)
+. IR (KBr, cm
-1): ν 2979,2940, and 1732,1667,1625,1600,1586,1525,1464,1410,1384,1357. above digital proof gained compounds are object product.
Embodiment 46:
In reaction flask, pack successively Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), benzene 8 mL, compound 3 b (10 mmol), TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 5 a, yield is 75 %.
Product is analyzed, and result is as follows:
1h NMR (400 MHz, CDCl
3) δ 7.71 (d,
j=6.9 Hz, 2H), 7.29 (d,
j=7.2 Hz, 2H), 5.62 (s, 1H), 4.35 (q,
j=6.4 Hz, 2H), 3.24 – 2.85 (m, 4H), 1.56 (d,
j=6.5 Hz, 4H), 1.26 (t,
j=6.6 Hz, 3H), 1.19 (s, 9H), 0.79 (t,
j=6.0 Hz, 6H).
13C NMR (100 MHz, CDCl 3 ) δ 186.1,165.7,154.5,154.2,137.0,127.0,124.7,90.4,61.6,52.5,34.5,30.8,20.4,13.6,10.9.hRMS For C
22h
34nO
3: 360.2539, Found:360.2513 (M+1)
+. IR (KBr, cm
-1): ν 2965,2928, and 1737,1631,1606,1562,1530,1470,1383,1366. above digital proof gained compounds are object product.
Embodiment 47:
In reaction flask, pack successively Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), benzene 8 mL, compound 3 c (10 mmol), TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 5 b, yield is 70 %.
Product is analyzed, and result is as follows:
1h NMR (400 MHz, CDCl
3) δ 7.72 (d,
j=8.0 Hz, 2H), 7.32 (d,
j=8.0 Hz, 2H), 5.63 (s, 1H), 4.38 (q,
j=6.9 Hz, 2H), 3.26 – 2.98 (m, 4H), 1.57 (t,
j=6.7 Hz, 4H), 1.41 – 1.04 (m, 16H), 0.86 (t,
j=7.1 Hz, 6H).
13c NMR (100 MHz, CDCl
3) δ 185.6,165.3,154.2,153.8,136.8,126.7,124.4,90.0,61.3,52.5,34.2,30.5,27.3,19.4,13.3,13.1. HRMS For C
24h
38nO
3: 388.2852, Found:388.2829 (M+1)
+. IR (KBr, cm
-1): ν 2962,2933, and 1737,1632,1606,1562,1528,1,463 1383,1357. above digital proof gained compounds are object product.
Embodiment 48:
In reaction flask, pack successively Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a(6 mmol), benzene 8 mL, compound 3 d (10 mmol), TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product product 5 c, yield is 64 %.
Product is analyzed, and result is as follows:
1h NMR (400 MHz, CDCl
3) δ 7.80 (d,
j=8.1 Hz, 2H), 7.42 (d,
j=8.1 Hz, 2H), 5.74 (s, 1H), 4.47 (d,
j=7.1 Hz, 2H), 3.10 (d,
j=7.3 Hz, 4H), 2.17 (s, 2H), 1.38 (t,
j=7.1 Hz, 3H), 1.32 (s, 9H), 0.93 (d,
j=6.4 Hz, 12H).
13c NMR (100 MHz, CDCl
3) δ 186.0,165.5,155.0,154.1,137.0,126.9,124.6,91.9,61.5,58.4,34.4,34.4,30.9,30.8,26.2,19.7,13.5. HRMS For C
24h
38nO
3: 388.2852, Found:388.2822 (M+1)
+. IR (KBr, cm
-1): ν 2962,2930, and 1737,1633,1526,1464,1445,1384,1356. above digital proof gained compounds are object product.
Embodiment 49:
In reaction flask, pack successively Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), benzene 8 mL, compound 3 e (10 mmol), TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 5 d, yield is 85 %.
Product is analyzed, and result is as follows:
1h NMR (400 MHz, CDCl
3) δ 7.71 (d,
j=6.9 Hz, 2H), 7.29 (d,
j=7.2 Hz, 2H), 5.62 (s, 1H), 4.35 (q,
j=6.4 Hz, 2H), 3.24 – 2.85 (m, 4H), 1.56 (d,
j=6.5 Hz, 4H), 1.26 (t,
j=6.6 Hz, 3H), 1.19 (s, 9H), 0.79 (t,
j=6.0 Hz, 6H).
13C NMR (100 MHz, CDCl 3 ) δ 186.1,165.7,154.5,154.2,137.0,127.0,124.7,90.4,61.6,52.5,34.5,30.8,20.4,13.6,10.9.hRMS For C
22h
34nO
3: 360.2539, Found:360.2513 (M+1)
+. IR (KBr, cm
-1): ν 2965,2928, and 1737,1631,1606,1562,1530,1470,1383,1366. above digital proof gained compounds are object product.
Embodiment 50:
In reaction flask, pack successively Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a (2 mmol), compound 2 a(6 mmol), benzene 8 mL, compound 3 f (10 mmol), TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 5 e, yield is 95 %.
Product is analyzed, and result is as follows:
1h NMR (400 MHz, CDCl
3) δ 7.72 (d,
j=8.0 Hz, 2H), 7.32 (d,
j=8.0 Hz, 2H), 5.63 (s, 1H), 4.38 (q,
j=6.9 Hz, 2H), 3.26 – 2.98 (m, 4H), 1.57 (t,
j=6.7 Hz, 4H), 1.41 – 1.04 (m, 16H), 0.86 (t,
j=7.1 Hz, 6H).
13c NMR (100 MHz, CDCl
3) δ 185.6,165.3,154.2,153.8,136.8,126.7,124.4,90.0,61.3,52.5,34.2,30.5,27.3,19.4,13.3,13.1. HRMS For C
24h
38nO
3: 388.2852, Found:388.2829 (M+1)
+. IR (KBr, cm
-1): ν 2962,2933, and 1737,1632,1606,1562,1528,1,463 1383,1357. above digital proof gained compounds are object product.
Embodiment 51:
In reaction flask, pack successively Co (acac) into
2(0.4 mmol), cesium carbonate Cs
2cO
3(6 mmol), compound 1 a(2 mmol), compound 2 a (6 mmol), benzene 8 mL, compound 3 g (10 mmol), TBHP(12 mmol), then this system heated under 80 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (10 mL * 3), anhydrous sodium sulfate drying organic layer, by simple column chromatography, get final product to obtain product 5 f, yield is 92 %.
Product is analyzed, and result is as follows:
1h NMR (400 MHz, CDCl
3) δ 7.72 (d,
j=8.4 Hz, 2H), 7.32 (d,
j=8.4 Hz, 2H), 5.63 (s, 1H), 4.38 (q,
j=7.1 Hz, 2H), 3.31 – 2.97 (m, 4H), 1.58 (s, 4H), 1.33 – 1.19 (m, 24H), 0.81 (t,
j=6.1 Hz, 6H).
13c NMR (100 MHz, CDCl
3) δ 186.0,165.7,154.4,154.1,137.0,127.0,124.7,90.3,61.6,50.9,34.5,31.0,30.8,26.1,22.1,13.58,13.57. HRMS For C
28h
46nO
3: 444.2478, Found:444.2458 (M+1)
+. IR (KBr, cm
-1): ν 2958,2931, and 1737,1631,1606,1561,1529,1466,1383,1357. above digital proof gained compounds are object product.
Claims (1)
1. a method of preparing β-unsaturated enamine ester derivative, it is characterized in that, comprise the following steps: under the existence of alkali, take styrene derivatives, amine and Bromodifluoroacetic acid ethyl ester is reactant, take cobalt compound as catalyzer, take trimethyl carbinol hydrogen peroxide as oxygenant, in water or organic solvent, by three component free radical cross-coupling reactions, obtain product β-unsaturated enamine ester;
The structural formula of described styrene derivatives is:
in formula, Ar is selected from: a kind of in the 4-aminophenyl of phenyl, 4-tert-butyl-phenyl, 4-p-methoxy-phenyl, 4-cyano-phenyl, 4-aminomethyl phenyl, 4-bromophenyl, 4-chloro-phenyl-, 3-bromophenyl, naphthyl, 4-fluorophenyl, 3-fluorophenyl, 3-trifluoromethyl and tertiary butyl oxycarbonyl protection;
Described amine is selected from: a kind of in triethylamine, tripropyl amine, Tributylamine, triisobutyl amine, dipropyl amine, dibutylamine, dihexylamine;
Described cobalt compound is acetylacetone cobalt (II);
Described alkali is cesium carbonate.
2. the preparation method of β-unsaturated enamine ester derivative according to claim 1, is characterized in that: described organic solvent is benzene, DMF, toluene, acetonitrile, 1,2-ethylene dichloride or 1，1，1-trichloroethane or tetrahydrofuran (THF).
3. the preparation method of β-unsaturated enamine ester derivative according to claim 2, is characterized in that: described organic solvent is benzene.
4. the preparation method of β-unsaturated enamine ester derivative according to claim 1, it is characterized in that, according to molar ratio computing, the consumption of catalyzer is styrene derivatives 5～40%; The consumption of Bromodifluoroacetic acid ethyl ester is 2～5 times of styrene derivatives; The consumption of amine is 3～10 times of styrene derivatives; The consumption of oxygenant is 1～10 times of styrene derivatives; The consumption of alkali is 2～6 times of styrene derivatives.
5. the preparation method of β-unsaturated enamine ester derivative according to claim 4, it is characterized in that, according to molar ratio computing, the consumption of catalyzer is styrene derivatives 20%; The consumption of Bromodifluoroacetic acid ethyl ester is 3 times of styrene derivatives; The consumption of amine is 5 times of styrene derivatives; The consumption of oxygenant is 6 times of styrene derivatives; The consumption of alkali is 3 times of styrene derivatives.
6. the preparation method of β-unsaturated enamine ester derivative according to claim 1, it is characterized in that, the temperature of reaction of described three component free radical cross-coupling reactions is 60～100 ℃; Reaction times is 12～24 hours.
7. the preparation method of β-unsaturated enamine ester derivative according to claim 6, it is characterized in that, the temperature of reaction of described three component free radical cross-coupling reactions is 80 ℃; Reaction times is 12 hours.
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