Synthesis method of alpha, beta-unsaturated acrylonitrile derivative by visible light catalysis
阅读说明：本技术 可见光催化α,β-不饱和丙烯腈衍生物的合成方法 (Synthesis method of alpha, beta-unsaturated acrylonitrile derivative by visible light catalysis ) 是由 许孝良 陈佳威 倪念念 吴琼 于 2021-09-30 设计创作，主要内容包括：本发明公开了一种可见光催化α,β-不饱和丙烯腈衍生物的合成方法。所述合成方法是：在反应溶剂中,以式(III)所示的N,N-二甲基苯胺化合物和式(II)所示的Baylis-Hillman衍生物为原料,在惰性气体或N-(2)保护、可见光光照条件以及光催化剂作用下,于室温常压下充分搅拌反应,之后反应混合物经后处理得到式(I)所示的α,β-不饱和丙烯腈衍生物。本发明所述合成方法具有反应条件温和、易于操作、广泛的官能团耐受性、可见光催化剂使用量低、收率高等优点。(The invention discloses a method for synthesizing a visible light catalytic alpha, beta-unsaturated acrylonitrile derivative. The synthesis method comprises the following steps: in a reaction solvent, taking an N, N-dimethylaniline compound shown in a formula (III) and a Baylis-Hillman derivative shown in a formula (II) as raw materials, and reacting in an inert gas or N 2 Under the conditions of protection, visible light illumination and the action of a photocatalyst, the mixture is fully stirred and reacted at room temperature and normal pressure, and then the reaction mixture is subjected to post-treatment to obtain the alpha, beta-unsaturated acrylonitrile derivative shown in the formula (I). The synthesis method has the advantages of mild reaction conditions, easy operation and wide application rangeThe universal functional group tolerance, the low use amount of the visible light catalyst, the high yield and the like.)
1. A synthetic method of an alpha, beta-unsaturated acrylonitrile derivative shown as a formula (I) comprises the following steps: in a reaction solvent, taking an N, N-dimethylaniline compound shown in a formula (III) and a Baylis-Hillman derivative shown in a formula (II) as raw materials, and reacting in an inert gas or N2Under the protection, visible light illumination and photocatalyst action in a roomFully stirring at normal temperature and pressure for reaction, and then carrying out post-treatment on the reaction mixture to obtain the alpha, beta-unsaturated acrylonitrile derivative shown in the formula (I); the photocatalyst is selected from the following compounds: ru (phen)3(BF4)2、Ru(bpy)3(BF4)2、[Ir(dFCF3ppy)2(dtbpy)]PF6、Ru(bpy)3(PF6)2(ii) a The reaction solvent is selected from one or any combination of the following: dimethyl sulfoxide, N-dimethylformamide and dichloromethane; the reaction formula is shown as follows:
wherein R is1Is a nitrogen-containing cyclic group substituted by C3-C6 cycloalkyl, C1-C6 alkyl or N-tert-butoxycarbonyl, R2、R3Each independently selected from hydrogen, C1-C4 alkyl, C1-C4 alkoxy, or halogen.
2. The method of synthesis of claim 1, wherein: the N-tert-butoxycarbonyl substituted nitrogen-containing cyclic group is N-tert-butoxycarbonylpiperidyl.
3. The method of synthesis of claim 2, wherein: r1Cyclohexyl, cyclopentyl, straight or branched butyl, straight or branched pentyl or N-tert-butoxycarbonylpiperidinyl.
4. A method of synthesis according to any one of claims 1 to 3, characterized in that: r2、R3At least one of them is hydrogen.
5. The method of synthesis of claim 1 or 4, wherein: r2、R3Each independently selected from hydrogen, methyl, methoxy, chloro or bromo.
6. The method of synthesis according to any one of claims 1 to 5, characterized in that: the alkali is one of sodium acetate, dipotassium hydrogen phosphate, sodium carbonate, sodium bicarbonate, tripotassium phosphate and triethylene diamine.
7. The method of synthesis according to any one of claims 1 to 5, characterized in that: the ratio of the Baylis-Hillman derivative shown in the formula (II) to the amount of the alkali feeding substance is 1: 1-2, and preferably 1: 1.2; the ratio of the Baylis-Hillman derivative shown in the formula (II) to the N, N-dimethylaniline compound shown in the formula (III) is 1: 1-2, preferably 1: 1.2; the ratio of the Baylis-Hillman derivative shown in the formula (II) to the photocatalyst feeding substance is 1: 0.0001-0.01, and the most preferable ratio is 1: 0.001; the volume usage amount of the reaction solvent is 2-6 mL/mmol based on the amount of Baylis-Hillman derivative substances shown in the formula (II).
8. The method of synthesis according to any one of claims 1 to 5, characterized in that: the light source of the visible light is selected from one of the following: a 25-45W white light energy-saving lamp and a 7W-14W blue light LED lamp.
9. The method of synthesis according to any one of claims 1 to 5, characterized in that: the reaction time is 4-24 h, preferably 6-8 h.
10. The method of synthesis according to any one of claims 1 to 5, characterized in that: the photocatalyst is Ru (phen)3(BF4)2The reaction solvent is dimethyl sulfoxide, the base is sodium acetate, and the ratio of the Baylis-Hillman derivative shown in the formula (II) to the N, N-dimethylaniline compound shown in the formula (III) is 1: 1.2; the ratio of the amounts of the charge materials of the Baylis-Hillman derivative represented by the following formula (II) to the N, N-dimethylaniline compound represented by the formula (III) is 1: 1.2; the ratio of the Baylis-Hillman derivative shown in the formula (II) to the amount of the photocatalyst feeding substance is 1: 0.001; the light source of the visible light is a 7W blue light LED lamp, and the reaction time is 6-8 h.
(I) technical field
The invention relates to a synthetic method of an alpha, beta-unsaturated acrylonitrile derivative.
(II) background of the invention
The alpha, beta-unsaturated nitrile is an important organic compound and has unique application in the fields of agricultural chemicals, dyes, medicines, functional materials and the like. Meanwhile, cyano is easily converted into important intermediates such as amides, acids, esters and the like in organic synthesis, wherein the alpha, beta-unsaturated acrylonitrile derivative is one of the most important monomers in organic synthesis, has irreplaceable effects in medicines and pesticides, can be used as an anticancer drug and a herbicide, such as entacapone (used for treating Parkinson disease) and CC-5079, and is an effective antitumor agent.
Traditional methods have focused primarily on the bifunctional of alkynes and direct cyanation of alkene C-H bonds or C-X to form substituted cyanoalkenes. Document A [ J.Am.chem.Soc.2007,129,2428-2429] reports preparation of trisubstituted acrylonitrile derivatives by taking aryl cyanide or aryl acetyl nitrile and alkyne as reaction substrates under nickel catalysis for the first time. Chem.commu.2011, 47, 2375-2377 reports that gallium metal catalyzes the reaction of arylacetylene and cyanogen bromide, and that gallium metal can selectively introduce a cyano group into a carbon-carbon triple bond. Document B [ chem.Commun.2013,49,6516-6518] reports rhodium catalyzed intramolecular addition of styrene and cyanide to produce tri-substituted acrylonitrile derivatives by cleavage of N-CN bonds and direct C-H bond cyanation, and document C [ org.Lett.2014,16,2158-2161] reports direct cyanation of alkenyl halides with acetone cyanohydrin under palladium catalysis to form tri-substituted acrylonitrile derivatives. The synthesis of substituted acrylonitrile derivatives is carried out in a number of ways, but most often with expensive catalysts or harsh reaction conditions, depending to some extent on the use of pre-functionalized olefins. In view of the importance of acrylonitrile derivatives, the development of simple, mild synthetic methods is still of some interest.
Disclosure of the invention
The invention aims to provide a method for synthesizing alpha, beta-unsaturated acrylonitrile derivatives by using visible light to catalyze the reaction of N, N-dimethylaniline compounds and Baylis-Hillman derivatives, and the method has the advantages of mild reaction conditions, easiness in operation, wide functional group tolerance, low use amount of visible light catalysts, high yield and the like.
In order to achieve the purpose, the invention adopts the following technical scheme:
a synthetic method of an alpha, beta-unsaturated acrylonitrile derivative shown as a formula (I) comprises the following steps: in a reaction solvent, taking an N, N-dimethylaniline compound shown in a formula (III) and a Baylis-Hillman derivative shown in a formula (II) as raw materials, and reacting in an inert gas or N2Under the conditions of protection, visible light illumination and the action of a photocatalyst, fully stirring the mixture at room temperature and normal pressure for reaction, and then carrying out post-treatment on the reaction mixture to obtain an alpha, beta-unsaturated acrylonitrile derivative shown in a formula (I); the photocatalyst is selected from the following compounds: ru (phen)3(BF4)2、Ru(bpy)3(BF4)2、[Ir(dFCF3ppy)2(dtbpy)]PF6、Ru(bpy)3(PF6)2(ii) a The reaction solvent is selected from one or any combination of the following: dimethyl sulfoxide, N-dimethylformamide and dichloromethane; the reaction formula is shown as follows:
wherein R is1Is a nitrogen-containing cyclic group substituted by C3-C6 cycloalkyl, C1-C6 alkyl or N-tert-butoxycarbonyl, R2、R3Each independently selected from hydrogen, C1-C4 alkyl, C1-C4 alkoxy, or halogen.
Preferably, the N-t-butoxycarbonyl-substituted nitrogen-containing cyclic group is N-t-butoxycarbonylpiperidinyl.
Preferably, R1Cyclohexyl, cyclopentyl, straight or branched butyl (e.g., N-butyl, isobutyl), straight or branched pentyl (e.g., N-pentyl) or N-tert-butoxycarbonylpiperidinyl (e.g., N-tert-butoxycarbonyl-4-piperidinyl).
Preferably, R2、R3At least one of them is hydrogen.
Preferably, R2、R3Each independently selected from hydrogen,Methyl, methoxy, chlorine or bromine. In a further preferred embodiment, R2、R3At least one of them is hydrogen.
The synthesis method of the photocatalyst used in the present invention is derived from the following documents:
1、Beilstein J.Org.Chem.2015,11,61；
2、J.Am.Chem.Soc.2013,125,7377；
3、J.Am.Chem.Soc.2004,126,2763；
4、Chem.Mater.2005,17,5712。
the choice of photocatalyst in the present invention has a significant impact on product yield. Preferably, the photocatalyst is Ru (phen)3(BF4)2。
In the present invention, the choice of reaction solvent will affect the product yield. Preferably, the reaction solvent is dimethyl sulfoxide. Preferably, the volume of the reaction solvent is 2 to 6mL/mmol based on the amount of the Baylis-Hillman derivative represented by the formula (II).
Preferably, the photocatalyst is Ru (phen)3(BF4)2The reaction solvent is dimethyl sulfoxide.
More preferably, the base is one of sodium acetate, dipotassium hydrogen phosphate, sodium carbonate, sodium hydrogen carbonate, tripotassium phosphate, and triethylenediamine, and most preferably sodium acetate.
Preferably, the Baylis-Hillman derivative represented by the formula (II) and the base charge material are used in a ratio of 1:1 to 2, preferably 1: 1.2.
Preferably, the ratio of the Baylis-Hillman derivative shown in the formula (II) to the N, N-dimethylaniline compound shown in the formula (III) is 1: 1-2, preferably 1: 1.2.
Preferably, the ratio of the Baylis-Hillman derivative represented by the formula (II) to the amount of the photocatalyst charging material is 1:0.0001 to 0.01, and most preferably 1:0.001, and if the amount of the catalyst is too small, the yield of the target product is lowered, and if the amount of the catalyst is too large, the yield is not significantly increased.
Preferably, the light source of the visible light is selected from one of the following: a 25-45W white light energy-saving lamp and a 7W-14W blue light LED lamp. Most preferred light sources are: the 7W blue LED lamp has the shortest reaction time.
Preferably, the reaction time is 4 to 24 hours, more preferably 6 to 8 hours.
As a particularly preferred embodiment, the photocatalyst is Ru (phen)3(BF4)2The reaction solvent is dimethyl sulfoxide, the base is sodium acetate, and the ratio of the Baylis-Hillman derivative shown in the formula (II) to the N, N-dimethylaniline compound shown in the formula (III) is 1: 1.2; the ratio of the amounts of the charge materials of the Baylis-Hillman derivative represented by the following formula (II) to the N, N-dimethylaniline compound represented by the formula (III) is 1: 1.2; the ratio of the Baylis-Hillman derivative shown in the formula (II) to the amount of the photocatalyst feeding substance is 1: 0.001; the light source of the visible light is a 7W blue light LED lamp, and the reaction time is 6-8 h.
The method for the work-up of the reaction mixture obtained by the reaction of the invention is recommended to be as follows: washing the reaction mixture with distilled water, extracting with diethyl ether, drying the obtained organic phase with anhydrous sodium sulfate, drying the solvent with a rotary evaporator, and separating by silica gel column chromatography, wherein an eluent is ethyl acetate/petroleum ether with the volume ratio of 1: 10-20, and finally the alpha, beta-unsaturated acrylonitrile derivative shown in the formula (I) is obtained.
Compared with the prior art, the invention has the beneficial effects that: the invention can react at room temperature and normal pressure without adding other additives, the usage amount of the catalyst is extremely low, and the reaction yield is high; and the method adopts visible light catalysis, has the characteristics of no pollution, environmental friendliness and the like, and has a wide prospect.
(IV) description of the drawings
FIG. 1 shows the preparation of 2- (cyclohexylmethylene) -4- (methyl (phenyl) amino) butanenitrile1HNMR spectrogram.
FIG. 2 is a scheme showing the preparation of 2- (cyclohexylmethylene) -4- (methyl (phenyl) amino) butanenitrile13CNMR spectrogram.
(V) detailed description of the preferred embodiments
The technical features of the technical solutions provided by the present invention will be further clearly and completely described below with reference to the specific embodiments, and it should be apparent that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
In order to achieve the above purpose, the invention adopts the following technical scheme.
Catalyst Ru (phen) used in the embodiment of the invention3(BF4)2The structural formula of (A) is as follows:
example 1
To a 25ml Schlenk tube, 0.5mmol of R was added in order1Cyanopropene as cyclohexyl radical, 0.6mmol R2、R3N, N-dimethylaniline as hydrogen, 0.0005mmol Ru (phen)3(BF4)20.6mmol of sodium acetate, changing nitrogen in a double-row tube for three times in vacuum, adding 4ml of dimethyl sulfoxide in the nitrogen atmosphere, and stirring for 8 hours at room temperature under a 7W blue light LED lamp. After the reaction is finished, the reaction solution is washed by distilled water and extracted by diethyl ether for three times, organic phases are combined, dried by anhydrous sodium sulfate, rotated to remove the solvent, and separated and purified by silica gel column chromatography (column chromatography developing agent: ethyl acetate/petroleum ether ═ 1: 10-20) to obtain the target product 2- (cyclohexylmethylene) -4- (methyl (phenyl) amino) butyronitrile with the yield of 97%. Product characterization data were as follows:
1H NMR(400MHz,Chloroform-d)δ7.28–7.23(m,2H),6.75–6.69(m,3H),6.24(d,J＝10.1Hz,37/100×1H),5.97(d,J＝9.9Hz,63/100×1H),3.56(q,J＝7.2Hz,2H),2.99(s,37/100×3H),2.96(s,63/100×3H),2.56–2.51(m,37/100×1H),2.50–2.42(m,2H),2.22–2.13(m,67/100×1H),1.73–1.08(m,10H).
13C NMR(101MHz,Chloroform-d)δ155.23,155.19,148.43,148.23,129.38,129.34,120.18,117.75,117.75,116.67,116.55,112.17,110.15,109.67,51.27,51.22,40.90,39.14,38.92,37.89,31.97,31.91,31.83,26.30,25.60,25.51,25.26,25.24.
HRMS(ESI)m/z calcd for C18H25N2 +(M+H)+269.20123,found 269.20129.
example 2
To a 25ml Schlenk tube, 0.5mmol of R was added in order1Cyanopropene as cyclohexyl radical, 0.5mmol R2、R3N, N-dimethylaniline as hydrogen, 0.0005mmol Ru (phen)3(BF4)20.6mmol of sodium acetate, changing nitrogen in a double-row tube for three times in vacuum, adding 4ml of dimethyl sulfoxide in the nitrogen atmosphere, and stirring for 8 hours at room temperature under a 7W blue light LED lamp. After the reaction is finished, the reaction solution is washed by distilled water and extracted by diethyl ether for three times, organic phases are combined, dried by anhydrous sodium sulfate, rotated to remove the solvent, and separated and purified by silica gel column chromatography (column chromatography developing agent: ethyl acetate/petroleum ether ═ 1: 10-20) to obtain the target product 2- (cyclohexylmethylene) -4- (methyl (phenyl) amino) butyronitrile with the yield of 79%.
Example 3
To a 25ml Schlenk tube, 0.5mmol of R was added in order1Cyanopropene as cyclohexyl radical, 0.8mmol R2、R3N, N-dimethylaniline as hydrogen, 0.0005mmol Ru (phen)3(BF4)20.6mmol of sodium acetate, changing nitrogen in a double-row tube for three times in vacuum, adding 4ml of dimethyl sulfoxide in the nitrogen atmosphere, and stirring for 8 hours at room temperature under a 7W blue light LED lamp. After the reaction is finished, the reaction solution is washed by distilled water and extracted by diethyl ether for three times, organic phases are combined, dried by anhydrous sodium sulfate, rotated to remove the solvent, and separated and purified by silica gel column chromatography (column chromatography developing agent: ethyl acetate/petroleum ether ═ 1: 10-20) to obtain the target product 2- (cyclohexylmethylene) -4- (methyl (phenyl) amino) butyronitrile with the yield of 92 percent.
Example 4
To a 25ml Schlenk tube, 0.5mmol of R was added in order1Cyanopropene as cyclohexyl radical, 0.6mmol R2、R3N, N-dimethylaniline as hydrogen, 0.0005mmol Ru (phen)3(BF4)20.5mmol sodium acetate, exchanging nitrogen gas in a double-row vacuum three times, adding 4ml dimethyl under nitrogen atmosphereSulfoxide, stirred under 7W blue LED lamp for 8h at room temperature. After the reaction is finished, the reaction solution is washed by distilled water and extracted by diethyl ether for three times, organic phases are combined, dried by anhydrous sodium sulfate, rotated to remove the solvent, and separated and purified by silica gel column chromatography (column chromatography developing agent: ethyl acetate/petroleum ether ═ 1: 10-20) to obtain the target product 2- (cyclohexylmethylene) -4- (methyl (phenyl) amino) butyronitrile with the yield of 71%.
Example 5
To a 25ml Schlenk tube, 0.5mmol of R was added in order1Cyanopropene as cyclohexyl radical, 0.6mmol R2、R3N, N-dimethylaniline as hydrogen, 0.0005mmol Ru (bpy)3(BF4)20.6mmol of sodium acetate, changing nitrogen in a double-row tube for three times in vacuum, adding 4ml of dimethyl sulfoxide in the nitrogen atmosphere, and stirring for 8 hours at room temperature under a 7W blue light LED lamp. After the reaction is finished, the reaction solution is washed by distilled water and extracted by diethyl ether for three times, organic phases are combined, dried by anhydrous sodium sulfate, rotated to remove the solvent, and separated and purified by silica gel column chromatography (column chromatography developing agent: ethyl acetate/petroleum ether ═ 1: 10-20) to obtain the target product 2- (cyclohexylmethylene) -4- (methyl (phenyl) amino) butyronitrile with the yield of 67%.
Example 6
To a 25ml Schlenk tube, 0.5mmol of R was added in order1Cyanopropene as cyclohexyl radical, 0.6mmol R2、R3N, N-dimethylaniline as hydrogen, 0.0005mmol Ir (ppy)30.6mmol of sodium acetate, changing nitrogen in a double-row tube for three times in vacuum, adding 4ml of dimethyl sulfoxide in the nitrogen atmosphere, and stirring for 8 hours at room temperature under a 7W blue light LED lamp. After the reaction is finished, the reaction solution is washed by distilled water and extracted by diethyl ether for three times, organic phases are combined, dried by anhydrous sodium sulfate, rotated to remove the solvent, and separated and purified by silica gel column chromatography (column chromatography developing agent: ethyl acetate/petroleum ether ═ 1: 10-20) to obtain the target product 2- (cyclohexylmethylene) -4- (methyl (phenyl) amino) butyronitrile with the yield of 0%.
Example 7
To a 25ml Schlenk tube, 0.5mmol of R was added in order1Cyanopropene as cyclohexyl radical, 0.6mmol R2、R3N, N-dimethylaniline as hydrogen, 0.0005mmol [ Ir (dFCF)3ppy)2(dtbpy)]PF60.6mmol of sodium acetate, changing nitrogen in a double-row tube for three times in vacuum, adding 4ml of dimethyl sulfoxide in the nitrogen atmosphere, and stirring for 8 hours at room temperature under a 7W blue light LED lamp. After the reaction is finished, the reaction solution is washed by distilled water and extracted by diethyl ether for three times, organic phases are combined, dried by anhydrous sodium sulfate, rotated to remove the solvent, and separated and purified by silica gel column chromatography (column chromatography developing agent: ethyl acetate/petroleum ether ═ 1: 10-20) to obtain the target product 2- (cyclohexylmethylene) -4- (methyl (phenyl) amino) butyronitrile with the yield of 72%.
Example 8
To a 25ml Schlenk tube, 0.5mmol of R was added in order1Cyanopropene as cyclohexyl radical, 0.6mmol R2、R3N, N-dimethylaniline as hydrogen, 0.0005mmol Ru (bpy)3(PF6)20.6mmol of sodium acetate, changing nitrogen in a double-row tube for three times in vacuum, adding 4ml of dimethyl sulfoxide in the nitrogen atmosphere, and stirring for 8 hours at room temperature under a 7W blue light LED lamp. After the reaction is finished, the reaction solution is washed by distilled water and extracted by diethyl ether for three times, organic phases are combined, dried by anhydrous sodium sulfate, rotated to remove the solvent, and separated and purified by silica gel column chromatography (column chromatography developing agent: ethyl acetate/petroleum ether ═ 1: 10-20) to obtain the target product 2- (cyclohexylmethylene) -4- (methyl (phenyl) amino) butyronitrile with the yield of 63%.
Example 9
To a 25ml Schlenk tube, 0.5mmol of R was added in order1Cyanopropene as cyclohexyl radical, 0.6mmol R2、R3N, N-dimethylaniline as hydrogen, 0.0005mmol Ru (phen)3(BF4)20.6mmol of sodium acetate, changing nitrogen in a double-row vacuum tube for three times, adding 4ml of N-methyl pyrrolidone in the nitrogen atmosphere, and stirring at room temperature for 8 hours under a 7W blue light LED lamp. After the reaction is finished, the reaction solution is washed by distilled water and extracted by diethyl ether for three times, organic phases are combined, dried by anhydrous sodium sulfate, rotated to remove the solvent, and separated and purified by silica gel column chromatography (column chromatography developing agent: ethyl acetate/petroleum ether ═ 1: 10-20) to obtain the target product 2- (cyclohexylmethylene) -4- (methyl (phenyl) amino) butyronitrile with the yield of 0%.
Example 10
In a 25ml Schlenk tube,adding 0.5mmol of R in turn1Cyanopropene as cyclohexyl radical, 0.6mmol R2、R3N, N-dimethylaniline as hydrogen, 0.0005mmol Ru (phen)3(BF4)20.6mmol of sodium acetate, changing nitrogen in a double-row vacuum tube for three times, adding 4ml of N, N-dimethylformamide under the nitrogen atmosphere, and stirring at room temperature for 8 hours under a 7W blue light LED lamp. After the reaction is finished, the reaction solution is washed by distilled water and extracted by diethyl ether for three times, organic phases are combined, dried by anhydrous sodium sulfate, rotated to remove the solvent, and separated and purified by silica gel column chromatography (column chromatography developing agent: ethyl acetate/petroleum ether ═ 1: 10-20) to obtain the target product 2- (cyclohexylmethylene) -4- (methyl (phenyl) amino) butyronitrile with the yield of 71%.
Example 11
To a 25ml Schlenk tube, 0.5mmol of R was added in order1Cyanopropene as cyclohexyl radical, 0.6mmol R2、R3N, N-dimethylaniline as hydrogen, 0.0005mmol Ru (phen)3(BF4)20.6mmol of sodium acetate, changing nitrogen in a double-row tube for three times in vacuum, adding 4ml of dichloromethane in the nitrogen atmosphere, and stirring for 8 hours at room temperature under a 7W blue light LED lamp. After the reaction is finished, the reaction solution is washed by distilled water and extracted by diethyl ether for three times, organic phases are combined, dried by anhydrous sodium sulfate, rotated to remove the solvent, and separated and purified by silica gel column chromatography (column chromatography developing agent: ethyl acetate/petroleum ether ═ 1: 10-20) to obtain the target product 2- (cyclohexylmethylene) -4- (methyl (phenyl) amino) butyronitrile with the yield of 62%.
Example 12
To a 25ml Schlenk tube, 0.5mmol of R was added in order1Cyanopropene as cyclohexyl radical, 0.6mmol R2、R3N, N-dimethylaniline as hydrogen, 0.0005mmol Ru (phen)3(BF4)20.6mmol of sodium acetate, changing nitrogen in a double-row tube for three times in vacuum, adding 4ml of acetonitrile in the nitrogen atmosphere, and stirring for 8 hours at room temperature under a 7W blue light LED lamp. After the reaction is finished, washing the reaction liquid with distilled water and extracting with diethyl ether for three times, combining organic phases, drying with anhydrous sodium sulfate, rotatably removing the solvent, and separating and purifying by silica gel column chromatography (column chromatography developing agent: ethyl acetate/petroleum ether ═ 1: 10-20) to obtain the target product 2- (cyclohexylmethylene) -4- (methyl (phenyl) amino) butylNitrile, yield 47%.
Example 13
To a 25ml Schlenk tube, 0.5mmol of R was added in order1Cyanopropene as cyclopentyl, 0.6mmol R2、R3N, N-dimethylaniline as hydrogen, 0.0005mmol Ru (phen)3(BF4)20.6mmol of sodium acetate, changing nitrogen in a double-row tube for three times in vacuum, adding 4ml of dimethyl sulfoxide in the nitrogen atmosphere, and stirring for 8 hours at room temperature under a 7W blue light LED lamp. After the reaction is finished, the reaction solution is washed by distilled water and extracted by diethyl ether for three times, organic phases are combined, dried by anhydrous sodium sulfate, rotated to remove the solvent, and separated and purified by silica gel column chromatography (column chromatography developing agent: ethyl acetate/petroleum ether ═ 1: 10-20) to obtain the target product 2- (cyclopentyl methylene) -4- (methyl (phenyl) amino) butyronitrile with the yield of 80%. Product characterization data were as follows:
1H NMR(400MHz,Chloroform-d)δ7.28–7.24(m,2H),6.75–6.70(m,3H),6.33(d,J＝10.1Hz,21/100×1H),6.04(d,J＝10.3Hz,79/100×1H),3.56(t,J＝7.1Hz,2H),2.99(s,21/100×3H),2.97(s,79/100×3H),2.94–2.79(m,79/100×1H),2.67–2.58(m,21/100×1H),2.53–2.44(m,2H),1.92–1.21(m,8H).
13C NMR(101MHz,Chloroform-d)δ155.05,154.88,148.45,148.37,129.35,129.34,120.15,117.90,116.69,116.56,112.22,112.19,110.24,109.94,51.25,42.58,39.24,38.95,38.85,33.12,32.96,31.75,26.36,25.48.
HRMS(ESI)m/z calcd for C17H23N2 +(M+H)+255.18558,found 255.18567.
example 14
To a 25ml Schlenk tube, 0.5mmol of R was added in order1Cyanopropene as cyclohexyl radical, 0.6mmol R2Is hydrogen, R3N, N-dimethylaniline as methyl group, 0.0005mmol Ru (phen)3(BF4)20.6mmol of sodium acetate, changing nitrogen in a double-row tube for three times in vacuum, adding 4ml of dimethyl sulfoxide in the nitrogen atmosphere, and stirring for 8 hours at room temperature under a 7W blue light LED lamp. After the reaction is finished, the reaction solution is washed by distilled water and extracted by diethyl ether for three times, organic phases are combined, dried by anhydrous sodium sulfate and rotatedThe solvent is removed, and the target product 2- (cyclohexylmethylene) -4- (methyl (p-tolyl) amino) butyronitrile is obtained by separation and purification through silica gel column chromatography (column chromatography developing agent: ethyl acetate/petroleum ether: 1: 10-20) with the yield of 88%. Product characterization data were as follows:
1H NMR(400MHz,Chloroform-d)δ7.07(dd,J＝8.6,2.6Hz,2H),6.65(dd,J＝8.6,3.9Hz,2H),6.23(d,J＝10.1Hz,32/100×1H),5.97(d,J＝9.9Hz,68/100×1H),3.52(m,2H),2.96(s,32/100×3H),2.93(s,68/100×3H),2.57–2.50(m,68/100×1H),2.48–2.40(m,2H),2.27(s,3H),2.23–2.16(m,32/100×1H),1.70–1.04(m,10H).
13C NMR(101MHz,CDCl3)δ155.05,154.98,146.47,146.31,129.88,129.86,126.06,125.94,120.19,117.75,112.69,110.29,109.84,51.64,51.58,40.89,39.19,39.06,37.87,32.00,31.95,31.72,26.17,25.62,25.56,25.28,25.27,20.27.
HRMS(ESI)m/z calcd for C19H27N2 +(M+H)+283.21688,found 283.21701.
example 15
To a 25ml Schlenk tube, 0.5mmol of R was added in order1Acrylonitrile as isobutyl, 0.6mmol R2、R3N, N-dimethylaniline as hydrogen, 0.0005mmol Ru (phen)3(BF4)20.6mmol of sodium acetate, changing nitrogen in a double-row tube for three times in vacuum, adding 4ml of dimethyl sulfoxide in the nitrogen atmosphere, and stirring for 8 hours at room temperature under a 7W blue light LED lamp. After the reaction is finished, the reaction solution is washed by distilled water and extracted by diethyl ether for three times, organic phases are combined, dried by anhydrous sodium sulfate, rotated to remove the solvent, and separated and purified by silica gel column chromatography (column chromatography developing agent: ethyl acetate/petroleum ether ═ 1: 10-20) to obtain the target product 4-methyl-2- (2- (methyl (phenyl) amino) ethyl) pent-2-enenitrile with the yield of 89%. Product characterization data were as follows:
1H NMR(400MHz,Chloroform-d)δ7.28–7.23(m,2H),6.76–6.70(m,3H),6.23(d,J＝10.2Hz,29/100×1H),5.96(d,J＝10.0Hz,71/100×1H),3.56(m,2H),2.99(s,29/100×3H),2.97(s,79/100×3H),2.87–2.78(m,71/100×1H),2.60–2.53(m,21/100×1H),2.51–2.42(m,2H),1.02(d,J＝6.6Hz,71/100×6H),0.97(d,J＝6.6Hz,29/100×6H).
13C NMR(101MHz,CDCl3)δ156.45,156.43,148.47,148.39,129.37,129.34,120.00,117.54,116.76,116.59,112.23,112.20,110.01,109.50,51.19,51.17,38.90,38.82,31.78,31.48,28.14,26.32,21.97,21.95.
HRMS(ESI)m/z calcd for C15H21N2 +(M+H)+229.16993,found 229.17007.
example 16
To a 25ml Schlenk tube, 0.5mmol of R was added in order1Acrylonitrile as n-pentyl group, 0.6mmol R2、R3N, N-dimethylaniline as hydrogen, 0.0005mmol Ru (phen)3(BF4)20.6mmol of sodium acetate, changing nitrogen in a double-row tube for three times in vacuum, adding 4ml of dimethyl sulfoxide in the nitrogen atmosphere, and stirring for 8 hours at room temperature under a 7W blue light LED lamp. After the reaction is finished, the reaction solution is washed by distilled water and extracted by diethyl ether for three times, organic phases are combined, dried by anhydrous sodium sulfate, rotated to remove the solvent, and separated and purified by silica gel column chromatography (column chromatography developing agent: ethyl acetate/petroleum ether ═ 1: 10-20) to obtain the target product 2- (2- (methyl (phenyl) amino) ethyl) hept-2-enenitrile with the yield of 87%. Product characterization data were as follows:
1H NMR(400MHz,Chloroform-d)δ7.26(t,J＝8.0Hz,2H),6.75–6.71(m,3H),6.42(t,J＝7.7Hz,22/100×1H),6.17(t,J＝7.7Hz,78/100×1H),3.58-3.53(m,2H),2.98(s,22/100×3H),2.97(s,78/100×3 2H),2.47(t,J＝7.2Hz,2H),2.36(q,J＝7.3Hz,78/100×2H),2.14–2.06(m,22/100×2H),1.43–1.27(m,4H),0.92(t,J＝7.0Hz,78/100×3H),0.87(t,J＝7.0Hz,22/100×3H).
13C NMR(101MHz,Chloroform-d)δ150.28,150.09,148.49,148.35,129.36,129.34,120.02,117.63,116.73,116.64,112.26,112.21,111.97,111.87,51.31,50.97,38.91,38.77,31.78,31.44,30.56,30.54,28.35,26.16,22.33,22.19,13.83,13.78.
HRMS(ESI)m/z calcd for C16H23N2 +(M+H)+243.18558,found 243.18570.
example 17
To a 25ml Schlenk tube, 0.5mmol of R was added in order1Propenenitrile N-tert-Butoxycarbonyl-4-piperidinyl, 0.6mmol of R2、R3N, N-dimethylaniline as hydrogen, 0.0005mmol Ru (phen)3(BF4)20.6mmol of sodium acetate, changing nitrogen in a double-row tube for three times in vacuum, adding 4ml of dimethyl sulfoxide in the nitrogen atmosphere, and stirring for 8 hours at room temperature under a 7W blue light LED lamp. After the reaction is finished, the reaction solution is washed by distilled water and extracted by diethyl ether for three times, organic phases are combined, dried by anhydrous sodium sulfate, rotated to remove the solvent, and separated and purified by silica gel column chromatography (column chromatography developing agent: ethyl acetate/petroleum ether ═ 1: 10-20) to obtain the target product, namely the 4- (2-cyano-4- (methyl (phenyl) amino) -1-alkene-1-yl) piperidine-1-carboxylic acid tert-butyl ester, with the yield of 67%. Product characterization data were as follows:
1H NMR(400MHz,Chloroform-d)δ7.28–7.23(m,2H),6.73(m,3H),6.19(d,J＝10.0Hz,27/100×1H),5.94(d,J＝9.7Hz,73/100×1H),4.10(s,2H),3.64–3.55(m,2H),3.01(s,27/100×3),2.97(s,73/100×3H),2.96–2.64(m,2H),2.69–2.60(m,73/100×1H),2.57–2.46(m,2H),2.25–2.17(m,23/100×1H),1.63–1.58(m,73/100×2H),1.47(s,73/100×9H),1.46(s,27/100×3H),1.38(d,J＝13.3Hz,27/100×1H),1.31–1.23(m,2H).
13C NMR(101MHz,Chloroform-d)δ154.69,154.59,152.83,152.72,148.42,148.00,129.42,129.35,119.67,117.35,116.80,116.71,112.24,112.11,111.79,111.31,79.69,79.65,51.06,50.97,43.01,42.90,39.73,39.09,38.84,36.11,31.93,30.75,30.66,28.45,28.43,26.61.
HRMS(ESI)m/z calcd for C22H32N3O2 +(M+H)+370.24890,found 370.24918.
example 18
To a 25ml Schlenk tube, 0.5mmol of R was added in order1Cyanopropene as cyclohexyl radical, 0.6mmol R2Is hydrogen, R3N, N-dimethylaniline as bromine, 0.0005mmol Ru (phen)3(BF4)20.6mmol sodium acetate, and nitrogen is exchanged in a double-row vacuum tubeNext, 4ml of dimethyl sulfoxide was added under nitrogen atmosphere, and stirred at room temperature for 8 hours under a 7W blue LED lamp. After the reaction is finished, the reaction solution is washed by distilled water and extracted by diethyl ether for three times, organic phases are combined, dried by anhydrous sodium sulfate, rotated to remove the solvent, and separated and purified by silica gel column chromatography (column chromatography developing agent: ethyl acetate/petroleum ether ═ 1: 10-20) to obtain the target product 4- ((4-bromophenyl) (methyl) amino) -2- (cyclohexylmethylene) butyronitrile with the yield of 93%. Product characterization data were as follows:
1H NMR(400MHz,Chloroform-d)δ7.32-7.26(m,2H),6.56-6.53(dd,J＝8.9,3,9Hz 2H),6.22(d,J＝10.1Hz,29/100×1H),5.94(d,J＝9.9Hz,71/100×1H),3.51(q,J＝7.4Hz,2H),2.95(s,29/100×3H),2.92(s,71/100×3H),2.54-2.47(m,79/100×1H),2.47–2.38(m,2H),2.16–2.11(m,21/100×1H),1.68–1.01(m,10H).
13C NMR(101MHz,CDCl3)δ155.40,155.28,147.42,147.24,131.97,131.94,120.02,117.61,113.78,113.73,109.95,109.46,108.56,108.45,51.18,51.15,40.88,39.27,39.00,37.93,31.92,31.88,31.75,26.23,25.57,25.48,25.24,25.21.
HRMS(ESI)m/z calcd for C18H24BrN2 +(M+H)+347.11174,found 347.11194.
example 19
To a 25ml Schlenk tube, 0.5mmol of R was added in order1Cyanopropene as cyclohexyl radical, 0.6mmol R2Is methoxy, R3N, N-dimethylaniline as hydrogen, 0.0005mmol Ru (phen)3(BF4)20.6mmol of sodium acetate, changing nitrogen in a double-row tube for three times in vacuum, adding 4ml of dimethyl sulfoxide in the nitrogen atmosphere, and stirring for 8 hours at room temperature under a 7W blue light LED lamp. After the reaction is finished, washing the reaction liquid with distilled water and extracting with diethyl ether for three times, combining organic phases, drying with anhydrous sodium sulfate, rotatably removing the solvent, and separating and purifying by silica gel column chromatography (column chromatography developing agent: ethyl acetate/petroleum ether ═ 1: 10-20) to obtain the target product 2- (cyclohexylmethylene) -4- ((3-methoxyphenyl) (methyl) amino) butyronitrile with the yield of 84%. Product characterization data were as follows:
1H NMR(400MHz,Chloroform-d)δ7.15(td,J＝8.2,3.1Hz,1H),6.34–6.23(m,3H),6.21-6.23(m，34/100×1H),5.97(d,J＝9.9Hz,66/100×1H),3.80(s,3H),3.54(q,J＝7.5Hz,2H),2.97(s,34/100×3H),2.95(s,66/100×3H),2.53–2.49(m,34/100×1H),2.48–2.41(m,2H),2.21–2.14(m,66/100×1H),1.70–1.04(m,10H).
13C NMR(101MHz,CDCl3)δ160.94,160.86,157.88,155.17,155.14,149.86,149.66,130.04,130.02,120.13,117.71,110.17,109.69,105.31,101.49,101.34,98.84,98.75,63.96,55.14,51.27,51.24,40.89,39.21,38.99,37.87,31.95,31.91,31.72,26.39,25.61,25.54,25.25,25.12.
HRMS(ESI)m/z calcd for C19H27N2O+(M+H)+299.21179,found 299.21204.
example 20
To a 25ml Schlenk tube, 0.5mmol of R was added in order1Cyanopropene as cyclohexyl radical, 0.6mmol R2、R3N, N-dimethylaniline as hydrogen, 0.0005mmol Ru (phen)3(BF4)20.6mmol of sodium acetate, changing nitrogen in a double-row pipe for three times in vacuum, adding 4ml of dimethyl sulfoxide in the nitrogen atmosphere, and stirring for 8 hours at room temperature under the dark condition. After the reaction is finished, the target product can not be detected by TLC.
Example 21
To a 25ml Schlenk tube, 0.5mmol of R was added in order1Cyanopropene as cyclohexyl radical, 0.6mmol R2、R3N, N-dimethylaniline as hydrogen and 0.6mmol sodium acetate, changing nitrogen in a double-row vacuum tube for three times, adding 4ml dimethyl sulfoxide in the nitrogen atmosphere, and stirring for 8 hours at room temperature under a 7W blue light LED lamp. After the reaction is finished, the target product can not be detected by TLC.
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