阅读说明：本技术 氰基芳基膦的制备方法 (Process for preparing cyanoarylphosphines ) 是由 赵万祥 李晨晨 张可卓 张明毫 于 2021-08-24 设计创作，主要内容包括：本发明公开了一种氰基芳基膦的制备方法,保护性气氛下,以乙氧基芳基甲腈与二取代的膦烷为原料,在碱和有机溶剂作用下发生反应制得氰基芳基膦。本发明以乙氧基芳基甲腈和二取代的膦烷为原料,无需金属催化剂,在碱的作用下实现不同取代基的氰基芳基膦的制备,操作简单,为不同取代基的氰基芳基膦的制备提供新型且快捷的途径。(The invention discloses a preparation method of cyanoaryl phosphine, which takes ethoxy aryl nitrile and disubstituted phosphine alkane as raw materials to react under the action of alkali and organic solvent under protective atmosphere to prepare the cyanoaryl phosphine. According to the invention, the ethoxy aryl carbonitrile and the disubstituted phosphine are used as raw materials, a metal catalyst is not needed, the preparation of the cyanoaryl phosphine with different substituents is realized under the action of alkali, the operation is simple, and a novel and rapid approach is provided for the preparation of the cyanoaryl phosphine with different substituents.)

1. A process for the preparation of a cyanoarylphosphine, characterized in that: under protective atmosphere, taking ethoxy aryl nitrile and disubstituted phosphine alkane as raw materials, and reacting under the action of alkali and an organic solvent to obtain the cyano aryl phosphine.

2. The method for producing a cyanoarylphosphine according to claim 1, wherein: and the aryl in the ethoxy aryl carbonitrile is substituted phenyl or fused ring aryl.

3. A process for the preparation of a cyanoaryl phosphine according to claim 2, wherein: the substituted phenyl is phenyl with at least one substituent of alkyl, alkoxy, alkenyl and diethylamino of C1-C5;

the condensed ring aryl is naphthyl, anthryl, phenanthryl or pyrenyl.

4. The method for producing a cyanoarylphosphine according to claim 1, wherein: the disubstituted phosphine alkane is diaryl substituted phosphine alkane or dialkyl substituted phosphine alkane.

5. The method for producing a cyanoarylphosphine according to claim 4, wherein: the diaryl substituted phosphine alkane is C1-C5 alkyl, alkoxy or trifluoromethyl substituted phenyl phosphine alkane, and is the same polysubstitution;

the dialkyl substituted phosphine alkane comprises alkyl of C1-C5, alkyl phosphine of cyclohexyl or adamantyl substituent, and is the same polysubstitution.

6. The method for producing a cyanoarylphosphine according to any one of claims 1 to 5, wherein: the mol ratio of the ethoxy aryl formonitrile, the disubstituted phosphine alkane and the alkali is 1: 1.0-1.5: 1.5 to 2.0.

7. The method for producing a cyanoarylphosphine according to any one of claims 1 to 5, wherein: the alkali is selected from at least one of lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium tert-butoxide, sodium tert-butoxide, potassium tert-butoxide, lithium bis (trimethylsilyl) amide, sodium bis (trimethylsilyl) amide and potassium bis (trimethylsilyl) amide.

8. The method for producing a cyanoarylphosphine according to any one of claims 1 to 5, wherein: the organic solvent is at least one selected from toluene, cyclohexane, 1, 4-dioxane, N, N-dimethylformamide and tetrahydrofuran.

9. The method for producing a cyanoarylphosphine according to any one of claims 1 to 5, wherein: the reaction temperature is 20-100 ℃.

10. The method for producing a cyanoarylphosphine according to any one of claims 1 to 5, wherein: the reaction time is 15-20 h.

Technical Field

The invention belongs to the technical field of organic synthesis, and relates to a preparation method of cyanoaryl phosphines with different substituents.

Background

Organophosphorus compounds are not only useful building blocks in organic synthesis, but also widely exist and are applied to life chemistry, pharmaceutical chemistry and catalytic ligands. For example, in organic synthesis, Wittig reagent has become an indispensable reagent for constructing carbon-carbon double bonds; the wide application of phosphorus-containing ligands (such as BINAP) in the reactions of transition metal-catalyzed coupling, asymmetric reduction and the like promotes the revolutionary development of metal organic chemistry, medical industry and functional materials; phosphorus-containing heterocycles also have important research values in life sciences. In addition, the organic phosphine compound can be used as a nucleophilic catalyst, and can also form coordinate bonds with vacant orbitals of transition metals through lone-pair electrons of phosphorus to construct different typesThe transition metal catalyst of (1). Organophosphine ligand (PR)₃) The chemical and physical properties of the transition metal catalyst can be influenced by the electron donating capability and the space size of the organic phosphine ligand, and the electron donating capability and the space size of the organic phosphine ligand can be regulated and controlled by changing the electrical property and the steric hindrance of the R group, so that the performance of the transition metal catalyst can be further regulated and controlled by changing the R group. If a chiral environment is introduced into the organic phosphine compound, the synthesis of the chiral catalyst and the application of the chiral catalyst in asymmetric catalysis can be realized. It follows that the position of organophosphinic compounds in organic synthesis is very important.

At present, the main synthesis method of the organic phosphorus compound is to construct pentavalent phosphine through transition metal catalysis, and then prepare trivalent organic phosphorus compound through reduction; in addition, the new trivalent organic phosphorus compound can be prepared by taking trivalent phosphine protected by borane as a raw material and carrying out chemical modification and reduction. These synthesis methods all require more than two steps to achieve the synthesis of the trivalent organophosphorus compounds, require transition metal catalysis, and require the use of highly toxic boranes. In addition, cyano groups as an effective functional group can be used to prepare the corresponding amines, aldehydes, amides and carboxylic acids by reduction and hydrolysis. Taking triaryl phosphine as an example, cyano group is introduced on aromatic ring to obtain cyanoaryl phosphine, and further conversion can prepare chiral phosphine ligand.

Disclosure of Invention

Aiming at the defects of the existing synthesis of different substituent cyanoaryl phosphines, the invention aims to provide a preparation method of different substituent cyanoaryl phosphines. The method is simple and convenient to operate, free of metal catalysis, non-toxic in used reaction reagent, green and environment-friendly, and provides a novel and quick approach for preparing the cyanoarylphosphine with different substituents.

In order to achieve the technical purpose, the invention adopts the following technical scheme:

the preparation method of the cyano aryl phosphine comprises the step of reacting ethoxy aryl carbonitrile and disubstituted phosphine alkane serving as raw materials under the action of alkali and an organic solvent in a protective atmosphere to prepare the cyano aryl phosphine.

Preferably, the aryl in the ethoxyarylcarbonitrile is a substituted phenyl group or a fused ring aryl group.

More preferably, the substituted phenyl is phenyl substituted by at least one substituent selected from alkyl, alkoxy, alkenyl and diethylamino of C1-C5;

the condensed ring aryl is naphthyl, anthryl, phenanthryl or pyrenyl.

Preferably, the disubstituted phosphine is a diaryl substituted phosphine or a dialkyl substituted phosphine.

More preferably, the diaryl substituted phosphine alkane is C1-C5 alkyl, alkoxy or trifluoromethyl substituted phenyl phosphine alkane, and is the same polysubstitution;

the dialkyl substituted phosphine alkane comprises alkyl of C1-C5, alkyl phosphine of cyclohexyl or adamantyl substituent, and is the same polysubstitution.

The term "identical polysubstitution" means that two aryl groups in the diaryl substituted phosphine are identical substituents; or dialkyl substituted phosphanes in which both alkyl groups are the same substituent.

Preferably, the mole ratio of the ethoxyarylcarbonitrile, the disubstituted phosphine alkane and the base is 1: 1.0-1.5: 1.5 to 2.0.

Preferably, the base is at least one selected from lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium tert-butoxide, sodium tert-butoxide, potassium tert-butoxide, lithium bistrimethylsilyl amide, sodium bistrimethylsilyl amide and potassium bistrimethylsilyl amide; more preferably at least one of lithium tert-butoxide, sodium tert-butoxide, and potassium tert-butoxide.

Preferably, the organic solvent is at least one selected from the group consisting of toluene, cyclohexane, 1, 4-dioxane, N-dimethylformamide, and tetrahydrofuran.

Preferably, the reaction temperature is 20-100 ℃; further preferably 60 to 80 ℃.

Preferably, the reaction time is 15-20 h.

The invention has the beneficial effects that:

according to the invention, the ethoxy aryl carbonitrile and the disubstituted phosphine are used as raw materials, a metal catalyst is not needed, the preparation of the cyanoaryl phosphine with different substituents is realized under the action of alkali, the operation is simple, and a novel and rapid approach is provided for the preparation of the cyanoaryl phosphine with different substituents. The cyanoaryl phosphine compounds prepared by the method can be further subjected to cyano functional group conversion to synthesize different chiral phosphine ligands.

Drawings

FIG. 1 is a nuclear magnetic hydrogen spectrum of a sample prepared in example 1 of the present invention;

FIG. 2 is a nuclear magnetic carbon spectrum of a sample obtained in example 1 of the present invention;

FIG. 3 is a nuclear magnetic phosphorus spectrum of a sample prepared in example 1 of the present invention;

FIG. 4 is a nuclear magnetic hydrogen spectrum of a sample prepared in example 2 of the present invention;

FIG. 5 is a nuclear magnetic carbon spectrum of a sample prepared in example 2 of the present invention;

FIG. 6 is a nuclear magnetic phosphorus spectrum of a sample prepared in example 2 of the present invention;

FIG. 7 is a nuclear magnetic hydrogen spectrum of a sample obtained in example 3 of the present invention;

FIG. 8 is a nuclear magnetic carbon spectrum of a sample obtained in example 3 of the present invention;

FIG. 9 is a nuclear magnetic phosphorus spectrum of a sample prepared in example 3 of the present invention;

FIG. 10 is a nuclear magnetic hydrogen spectrum of a sample obtained in example 4 of the present invention;

FIG. 11 is a nuclear magnetic carbon spectrum of a sample obtained in example 4 of the present invention;

FIG. 12 is a nuclear magnetic phosphorus spectrum of a sample obtained in example 4 of the present invention;

FIG. 13 is a nuclear magnetic hydrogen spectrum of a sample obtained in example 5 of the present invention;

FIG. 14 is a nuclear magnetic carbon spectrum of a sample obtained in example 5 of the present invention;

FIG. 15 is a nuclear magnetic phosphorus spectrum of a sample prepared in example 5 of the present invention;

FIG. 16 is a nuclear magnetic hydrogen spectrum of a sample obtained in example 6 of the present invention;

FIG. 17 is a nuclear magnetic carbon spectrum of a sample obtained in example 6 of the present invention;

FIG. 18 is a nuclear magnetic phosphorus spectrum of a sample prepared in example 6 of the present invention;

FIG. 19 is a nuclear magnetic hydrogen spectrum of a sample obtained in example 7 of the present invention;

FIG. 20 is a nuclear magnetic carbon spectrum of a sample obtained in example 7 of the present invention;

FIG. 21 is a nuclear magnetic phosphorus spectrum of a sample obtained in example 7 of the present invention.

Detailed Description

The invention is further illustrated with reference to specific examples. It should be noted that these examples are only for illustrating the present invention and do not limit the present invention in any way. However, the actual application of the invention will still be within the scope of the present invention as modified and modified by those skilled in the art. The reaction equations are shown in formula (1):

in the formula (1), NC-Ar-OEt is ethoxy aryl formonitrile,is disubstituted phosphine alkane.

Wherein Ar is substituted phenyl or condensed ring aryl;

further, the substituted phenyl is phenyl with at least one substituent of alkyl, alkoxy, alkenyl and diethylamino of C1-C5;

the condensed ring aryl is naphthyl, anthryl, phenanthryl or pyrenyl.

The disubstituted phosphine alkane is diaryl substituted phosphine alkane or dialkyl substituted phosphine alkane.

Further, the diaryl substituted phosphine alkane is C1-C5 alkyl, alkoxy or trifluoromethyl substituted phenyl phosphine alkane, and is the same polysubstitution;

the dialkyl substituted phosphine alkane comprises alkyl of C1-C5, alkyl phosphine of cyclohexyl or adamantyl substituent, and is the same polysubstitution.

It should be noted that the substitution position of CN-and-OEt on the benzene ring may be ortho-, meta-or para-position.

Example 1

5-diethylamino-2-ethoxybenzonitrile (1.09g, 5.0mmol, 1.0 equiv.), diphenylphosphinane (1.02g, 5.5mmol, 1.1 equiv.), potassium tert-butoxide (842mg, 7.5mmol, 1.5 equiv.) and cyclohexane (10mL) were added to a reaction flask under a nitrogen atmosphere. The mixed system is reacted for 15h at 80 ℃. After the reaction was completed, the reaction system was cooled to room temperature, diluted with dichloromethane, filtered, and subjected to column chromatography to obtain the objective product (1.61g, yield 90%).

The hydrogen spectrum data, the carbon spectrum data and the phosphorus spectrum data are respectively as follows:

¹H NMR(400MHz,CDCl₃)δ7.49(s,1H),7.36(d,J＝7.4Hz,10H),6.55(d,J＝8.5Hz,1H),6.05(s,1H),3.15(q,J＝7.2Hz,4H),0.96(t,J＝7.1Hz,6H).

¹³C NMR(100MHz,CDCl₃)δ149.7,143.3(d,J＝17.6Hz),135.4(d,J＝10.8Hz),135.1(d,J＝5.8Hz),134.0(d,J＝20.1Hz),129.2,128.7(d,J＝7.1Hz),119.6(d,J＝3.9Hz),116.2,110.7,101.7(d,J＝31.2Hz),44.6,12.2.

³¹P NMR(162MHz,CDCl₃)δ-7.5.

example 2

Under a nitrogen atmosphere, 4-ethoxybenzonitrile (736mg, 5.0mmol, 1.0 equiv.), diphenylphosphinane (1.02g, 5.5mmol, 1.1 equiv.), potassium tert-butoxide (842mg, 7.5mmol, 1.5 equiv.) and cyclohexane (10mL) were added to a reaction flask. The mixed system is reacted for 15h at 80 ℃. After the reaction was completed, the reaction system was cooled to room temperature, diluted with dichloromethane, filtered, and the solvent was dried by spinning to perform column chromatography to obtain the objective product (0.7g, yield 49%).

The hydrogen spectrum data, the carbon spectrum data and the phosphorus spectrum data are respectively as follows:

¹H NMR(400MHz,CDCl₃)δ7.58(d,J＝7.8Hz,2H),7.47–7.29(m,12H).

¹³C NMR(100MHz,CDCl₃)δ145.2(d,J＝16.7Hz),135.5(d,J＝10.5Hz),134.1(d,J＝20.2Hz),133.6(d,J＝18.5Hz),131.8(d,J＝6.1Hz),129.6,128.9(d,J＝7.5Hz),118.8,112.0.

³¹P NMR(162MHz,CDCl₃)δ-4.3.

example 3

To a reaction flask, under a nitrogen atmosphere, 3, 6-dimethyl-2-ethoxybenzonitrile (876mg, 5.0mmol, 1.0 equiv.), diphenylphosphinane (1.02g, 5.5mmol, 1.1 equiv.), potassium tert-butoxide (842mg, 7.5mmol, 1.5 equiv.) and cyclohexane (10mL) were added. The mixed system is reacted for 15h at 80 ℃. After the reaction was completed, the reaction system was cooled to room temperature, diluted with dichloromethane, filtered, and subjected to column chromatography to obtain the objective product (1.31g, yield 83%).

The hydrogen spectrum data, the carbon spectrum data and the phosphorus spectrum data are respectively as follows:

¹H NMR(400MHz,CDCl₃)δ7.41–7.33(m,10H),7.31–7.29(m,2H),2.53(s,3H),2.20(s,3H).

¹³C NMR(100MHz,CDCl₃)δ143.2(d,J＝13.2Hz),142.0(d,J＝4.8Hz),137.6(d,J＝24.0Hz),134.9(d,J＝3.1Hz),134.4(d,J＝12.3Hz),132.5(d,J＝19.1Hz),131.6,128.73,128.65(d,J＝3.3Hz),120.7(d,J＝23.8Hz),117.04(d,J＝4.0Hz),22.5(d,J＝15.2Hz),21.1.

³¹P NMR(162MHz,CDCl₃)δ-7.2.

example 4

To a reaction flask, 1-ethoxy-5, 6, 7, 8-tetrahydronaphthalene-2-carbonitrile (1.01g, 5.0mmol, 1.0 equiv.), diphenylphosphinane (1.02g, 5.5mmol, 1.1 equiv.), potassium tert-butoxide (842mg, 7.5mmol, 1.5 equiv.) and cyclohexane (10mL) were added under a nitrogen atmosphere. The mixed system is reacted for 15h at 80 ℃. After the reaction was completed, the reaction system was cooled to room temperature, diluted with dichloromethane, filtered, and subjected to column chromatography to obtain the objective product (1.43g, yield 84%).

The hydrogen spectrum data, the carbon spectrum data and the phosphorus spectrum data are respectively as follows:

¹H NMR(400MHz,CDCl₃)δ7.47(d,J＝8.0Hz,1H),7.42–7.28(m,10H),7.19(d,J＝8.0Hz,1H),2.88–2.75(m,4H),1.75–1.63(m,4H).

¹³C NMR(100MHz,CDCl₃)δ145.1(d,J＝18.3Hz),143.2(d,J＝4.3Hz),138.0(d,J＝24.5Hz),134.4(d,J＝11.7Hz),132.92(d,J＝19.4Hz),132.86(d,J＝2.8Hz),131.3,128.8,128.7(d,J＝6.4Hz),118.3(d,J＝2.7Hz),116.8(d,J＝12.9Hz),30.6,29.5(d,J＝23.9Hz),22.9(d,J＝3.6Hz),22.0.

³¹P NMR(162MHz,CDCl₃)δ-11.6.

example 5

To a reaction flask, under a nitrogen atmosphere, 2-ethoxy-1-naphthanenitrile (986mg, 5.0mmol, 1.0 equiv.), diphenylphosphinane (1.02g, 5.5mmol, 1.1 equiv.), potassium tert-butoxide (842mg, 7.5mmol, 1.5 equiv.) and cyclohexane (10mL) were added. The mixed system is reacted for 15h at 20 ℃. After the reaction was completed, the reaction system was cooled to room temperature, diluted with dichloromethane, filtered, and subjected to column chromatography to obtain the objective product (1.62g, 96% yield).

The hydrogen spectrum data, the carbon spectrum data and the phosphorus spectrum data are respectively as follows:

¹H NMR(400MHz,CDCl₃)δ8.31(d,J＝8.4Hz,1H),7.94(d,J＝8.3Hz,1H),7.89(d,J＝8.3Hz,1H),7.70(t,J＝7.8Hz,1H),7.62(t,J＝7.6Hz,1H),7.43–7.34(m,10H),7.21–7.16(m,1H).

¹³C NMR(100MHz,CDCl₃)δ143.5(d,J＝20.8Hz),135.2(d,J＝10.7Hz),134.0(d,J＝20.2Hz),133.3(d,J＝6.3Hz),132.7,132.5,129.5,128.99,128.97,128.90,128.6,128.1,125.4(d,J＝1.7Hz),116.7(d,J＝19.9Hz),116.5(d,J＝10.8Hz).

³¹P NMR(162MHz,CDCl₃)δ-7.1.

example 6

To a reaction flask, under a nitrogen atmosphere, 2-ethoxy-1-naphthonitrile (394mg, 2.0mmol, 1.0 equiv.), diamantalkylphosphine (0.665g, 2.2mmol, 1.1 equiv.), potassium bistrimethylsilyl amino (3.0mmol, 1.5 equiv.) and cyclohexane (10mL) were added. The mixed system is reacted for 15h at 80 ℃. After the reaction was completed, the reaction system was cooled to room temperature, diluted with dichloromethane, filtered, and subjected to column chromatography to obtain the objective product (0.48g, 53% yield).

The hydrogen spectrum data, the carbon spectrum data and the phosphorus spectrum data are respectively as follows:

¹H NMR(400MHz,CDCl₃)δ8.36(d,J＝8.3Hz,1H),7.98(s,2H),7.93(d,J＝8.2Hz,1H),7.72–7.60(m,2H),2.12–2.02(m,6H),2.00–1.88(m,12H),1.71–1.62(m,12H).

¹³C NMR(100MHz,CDCl₃)δ141.7(d,J＝32.1Hz),133.4(d,J＝9.2Hz),132.8,131.6(d,J＝2.6Hz),129.9,128.5,128.3,128.0,126.1,121.6(d,J＝42.0Hz),117.7(d,J＝5.0Hz),41.8(d,J＝12.4Hz),37.8(d,J＝23.8Hz),36.9,28.9(d,J＝8.7Hz).

³¹P NMR(162MHz,CDCl₃)δ-34.0.

example 7

To a reaction flask, under a nitrogen atmosphere, 2-ethoxybenzonitrile (0.74g, 5.0mmol, 1.0 equiv.), diphenylphosphinane (1.02g, 5.5mmol, 1.1 equiv.), potassium tert-butoxide (842mg, 7.5mmol, 1.5 equiv.) and cyclohexane (10mL) were added. The mixed system is reacted for 15h at 80 ℃. After the reaction was completed, the reaction system was cooled to room temperature, diluted with dichloromethane, filtered, and subjected to column chromatography to obtain the objective product (1.28g, yield 89%).

The hydrogen spectrum data, the carbon spectrum data and the phosphorus spectrum data are respectively as follows:

¹H NMR(400MHz,CDCl₃)δ7.71(d,J＝6.5Hz,1H),7.48(t,J＝7.6Hz,1H),7.45–7.27(m,11H),7.05(dd,J＝7.8,3.3Hz,1H).

¹³C NMR(100MHz,CDCl₃)δ143.1(d,J＝19.6Hz),134.7(d,J＝10.2Hz),134.1(d,J＝20.4Hz),133.8(d,J＝4.8Hz),133.5,132.5,129.5,129.0,128.9(d,J＝7.3Hz),117.9(d,J＝32.8Hz),117.7(d,J＝3.7Hz).

³¹P NMR(162MHz,CDCl₃)δ-8.6.

example 8

To a reaction flask, under a nitrogen atmosphere, 2-ethoxybenzonitrile (0.74g, 5.0mmol, 1.0 equiv.), diphenylphosphinane (1.02g, 5.5mmol, 1.1 equiv.), potassium hydroxide (420mg, 7.5mmol, 1.5 equiv.) and cyclohexane (10mL) were added. The mixed system is reacted for 15h at 80 ℃. After the reaction was completed, the reaction system was cooled to room temperature, diluted with dichloromethane, filtered, and the solvent was dried by spinning to perform column chromatography to obtain the objective product (0.57g, yield 20%).

Example 9

To a reaction flask, under a nitrogen atmosphere, 2-ethoxybenzonitrile (0.74g, 5.0mmol, 1.0 equiv.), diphenylphosphinane (1.02g, 5.5mmol, 1.1 equiv.), potassium bistrimethylsilyl amino (7.5mmol, 1.5 equiv.) and cyclohexane (10mL) were added. The mixed system is reacted for 15h at 80 ℃. After the reaction was completed, the reaction system was cooled to room temperature, diluted with dichloromethane, filtered, and subjected to column chromatography to obtain the objective product (0.14g, yield 5%).

Example 10

To a reaction flask, under a nitrogen atmosphere, 2-ethoxybenzonitrile (0.74g, 5.0mmol, 1.0 equiv.), diphenylphosphinane (1.02g, 5.5mmol, 1.1 equiv.), potassium tert-butoxide (842mg, 7.5mmol, 1.5 equiv.) and tetrahydrofuran (10mL) were added. The mixed system is reacted for 15h at 80 ℃. After the reaction was completed, the reaction system was cooled to room temperature, diluted with dichloromethane, filtered, and subjected to column chromatography to obtain the objective product (1.18g, yield 82%).