Method for arylating alpha position of tertiary amine
阅读说明：本技术 一种叔胺α位的芳基化方法 (Method for arylating alpha position of tertiary amine ) 是由 冯高峰 徐畅 沈方旗 于 2021-01-29 设计创作，主要内容包括：本发明公开了一种叔胺α位的芳基化方法,该方法首次以叔胺、苯甲腈衍生物为原料,使用无机碱,在有机溶剂中,可见光照射下搅拌一定时间,之后反应液经后处理,得到叔胺α位芳基化衍生物。本发明所用原料简单易得,反应条件绿色、温和,操作简单,不使用氧化剂和金属催化剂,反应体系不需要进行氮气保护和无水处理,具有很好工业化应用价值。(The invention discloses a method for arylating alpha-site of tertiary amine, which comprises the steps of taking tertiary amine and benzonitrile derivative as raw materials for the first time, stirring the raw materials for a certain time in an organic solvent under the irradiation of visible light by using inorganic base, and then carrying out post-treatment on reaction liquid to obtain the tertiary amine alpha-site arylated derivative. The method has the advantages of simple and easily obtained raw materials, green and mild reaction conditions, simple operation, no use of oxidant and metal catalyst, no need of nitrogen protection and anhydrous treatment of a reaction system, and good industrial application value.)
1. A process for the arylation of a tertiary amine at the α -position, characterized in that: the method comprises the following steps: mixing tertiary amine, a benzonitrile derivative and alkali in an organic solvent, stirring for reaction under the irradiation of visible light, and then carrying out post-treatment on a reaction solution to obtain a tertiary amine alpha-position arylation derivative; of alpha-arylated derivatives of said tertiary aminesStructural formula is One of (1);
wherein n is more than or equal to 1 and less than or equal to 3, and n is an integer;
R1is H, methyl or halogen atom, and the substituted position is ortho-position, meta-position and para-position, including mono-substitution and multi-substitution;
R2including but not limited to cyano, methoxycarbonyl, and R2The group is ortho-position monosubstitution, meta-position monosubstitution or para-position substitution;
R3is CmH2m+1，R4Is CmH2mM is not less than 1 and not more than 5, and m is an integer.
2. A process according to claim 1 for the arylation of a tertiary amine in the α -position, characterized in that: the organic solvent is one of N, N-dimethylacetamide, N-dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, acetonitrile and N-methylpyrrolidone.
3. A process according to claim 1 for the arylation of a tertiary amine in the α -position, characterized in that: the tertiary amine is selected from one of the following structural formulas:
4. a process according to claim 1 for the arylation of a tertiary amine in the α -position, characterized in that: the ratio of the tertiary amine, the benzonitrile derivative and the base is 2-4: 1: 2-4.
5. A process according to claim 1 for the arylation of a tertiary amine in the α -position, characterized in that: the cyanobenzene derivative includes, but is not limited to, 1, 2-cyanobenzene, 1, 3-dicyanobenzene, 1, 4-dicyanobenzene, methyl 4-cyanobenzoate.
6. A process according to claim 1 for the arylation of a tertiary amine in the α -position, characterized in that: the alkali is inorganic alkali, and comprises one of sodium carbonate, sodium acetate, potassium phosphate, potassium acetate, potassium carbonate, cesium carbonate and cesium acetate.
7. A process according to claim 1 for the arylation of a tertiary amine in the α -position, characterized in that: the visible light is blue light generated by the LED.
8. A process according to claim 1 for the arylation of a tertiary amine in the α -position, characterized in that: the stirring reaction time is 15-40 h, and the reaction temperature is room temperature.
9. A process according to claim 1 for the arylation of a tertiary amine in the α -position, characterized in that: the post-processing method comprises the following steps: after the reaction is finished, the generated product is subjected to extraction, rotary evaporation, column chromatography, rotary evaporation and pumping to obtain the tertiary amine alpha-position arylation derivative.
10. A process according to claim 1 for the arylation of a tertiary amine in the α -position, characterized in that: the structural formula of the tertiary amine alpha-position arylation derivative is one of the structural formulas shown in formulas (A) to (L):
Technical Field
The invention relates to the technical field of medicines, in particular to an arylation method of a tertiary amine alpha position.
Background
The tertiary amine compound is an important compound with various biological and physiological activities and is widely present in natural and non-natural products such as nimesulide, flutamide and the like. Functionalized tertiary arylamines, particularly tertiary arylamines modified by fragile groups (C-I, C-Br, C ≡ C, C ≡ O, C ═ N or/and C ═ N and the like), have important applications as important organic raw materials in the fields of medicines, pesticides, dyes, materials and the like, and the synthesis of the tertiary arylamines with green, high efficiency and atom economy is one of the important points of organic synthesis research.
In recent years, a great deal of modification work is carried out on C-H at alpha position of tertiary amine by chemists, and the obtained tertiary amine derivative can be used for synthesizing various drug intermediates. The work in the aspect not only enriches the variety of the tertiary amine derivatives, but also expands the application of the tertiary amine in the aspect of medicine. The synthesis of tertiary amine derivatives is of great importance. However, at present, most of the methods for modifying the C — H bond at the α -position of the tertiary amine are metal-catalyzed, and the like, and most of them use expensive metal catalysts for the coupling reaction and generally require a high-temperature reaction. Therefore, there is a need to develop some simple and green methods for structurally diverse modifications of tertiary amines.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide the tertiary amine alpha-position arylation method, the raw materials are simple and easy to obtain, the reaction conditions are green and mild, the operation is simple, an oxidant and a metal catalyst are not used, a reaction system does not need nitrogen protection and anhydrous treatment, and the method has good industrial application value.
In order to achieve the purpose, the invention adopts the following technical scheme:
a process for the arylation of a tertiary amine in the alpha position comprising the steps of: mixing tertiary amine, a benzonitrile derivative and alkali in an organic solvent, stirring for reaction under the irradiation of visible light, and then carrying out post-treatment on a reaction solution to obtain a tertiary amine alpha-position arylation derivative; the structural formula of the tertiary amine alpha-position arylation derivative is shown in the specification
One of (1);
wherein n is more than or equal to 1 and less than or equal to 3, and n is an integer;
R1is H, methyl or halogen atom, the substituted position is ortho-position, meta-position or para-position, including mono-substitution and multi-substitution, R1The substitution position is preferably ortho-position mono-substitution or multi-substitution, meta-position mono-substitution or multi-substitution and para-position substitution;
R2including but not limited to cyano, methoxycarbonyl, and R2The radical is ortho-position monosubstitution or meta-position monosubstitutionSubstitution or para-substitution;
R3is CmH2m+1，R4Is CmH2mM is not less than 1 and not more than 5, and m is an integer.
The organic solvent is one of N, N-dimethylacetamide, N-dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, acetonitrile and N-methylpyrrolidone.
The tertiary amine is selected from one of the following structural formulas:
the mass ratio of the tertiary amine, the benzonitrile derivative and the base is 2-4: 1: 2-4, preferably 2:1: 2.
The cyanobenzene derivative includes, but is not limited to, 1, 2-cyanobenzene, 1, 3-dicyanobenzene, 1, 4-dicyanobenzene, methyl 4-cyanobenzoate.
The alkali is inorganic alkali, and comprises one of sodium carbonate, sodium acetate, potassium phosphate, potassium acetate, potassium carbonate, cesium carbonate and cesium acetate.
The visible light is blue light generated by the LED.
The stirring reaction time is 15-40 h, and the reaction temperature is room temperature.
The post-processing method comprises the following steps: after the reaction is finished, the generated product is subjected to extraction, rotary evaporation, column chromatography, rotary evaporation and pumping to obtain the tertiary amine alpha-position arylation derivative.
The structural formula of the tertiary amine alpha-position arylation derivative is one of the structural formulas shown in formulas (A) to (L):
the invention has the beneficial effects that:
(1) the reaction conditions are mild: the raw materials are mixed and stirred at room temperature under the irradiation of blue light to generate a product.
(2) The reaction condition is green, and the operation is simple: the reaction does not need a metal catalyst, does not need an oxidant, and does not need to carry out water removal and oxygen-free operation on a reaction system.
(3) The tertiary amine and the cyanobenzene derivative are simple and easy to obtain, and the tertiary amine derivative with various structures and high purity can be easily obtained by changing raw materials.
Detailed Description
The invention is further described below with reference to specific embodiments:
example 1
The effect and effect of different bases on the reaction were examined: magnetons, 1-phenylpyrrolidine (0.75mmol), terephthalonitrile (0.5mmol), various bases (0.75mmol), and N, N-dimethylacetamide (5mL) were sequentially added to a 20mL reaction tube, and reacted for 16 hours under blue light irradiation at room temperature. The reaction solution was extracted with ethyl acetate, rotary distilled, and the yield was calculated by nuclear magnetic resonance hydrogen spectroscopy using 1,3, 5-trimethoxybenzene as an internal standard, as shown in table 1.
TABLE 1
Serial number
Alkali
Yield of
Examples 1 to 1
K3PO4
64％
Examples 1 to 2
KOAc
56％
Examples 1 to 3
K2CO3
66％
Examples 1 to 4
Cs2CO3
81％
And (3) analysis: comparison shows that Cs is used under the same other conditions2CO3The product obtained by catalysis has the highest yield and is cheap.
The products of examples 1 to 4 were reacted with1H-NMR and13C-NMR was carried out to determine,1H-NMR and13C-NMR data are as follows:
1H NMR(400MHz,CDCl3)δppm 7.61(d,J＝8.4Hz,2H),7.38(d,J＝8.0Hz,2H),7.21-7.16(m,2H),6.71(dd,J＝7.2,7.6Hz,1H),6.48(d,J＝7.6Hz,2H),4.78(dd,J＝8.8,2.4Hz,1H),3.80-3.75(m,1H),3.49-3.43(m,1H),2.51-2.43(m,1H),2.8-2.01(m,2H),1.97-1.92(m,1H).
13C NMR(100MHz,CDCl3)δppm 150.5,146.7,132.5(×2),129.2(×2),126.8(×2),119.0,116.5,112.4(×2),110.6,62.8,49.2,35.9,23.1.
the structural formula of the product is as follows:
example 2
The influence and effect of different solvents on the reaction were examined: magnetons, 1-phenylpyrrolidine (1.5mmol), terephthalonitrile (0.5mmol), and Cs were sequentially added to a 20mL reaction tube2CO3And a different solvent (5mL) were reacted at ambient temperature under blue light irradiation for 16 hours. Extracting the reaction liquid with ethyl acetate, rotary evaporating, and adding 1,3, 5-trimethoxy benzeneAs an internal standard, the yield was calculated by NMR spectroscopy, as shown in Table 2.
TABLE 2
Serial number
Organic solvent
Cs2CO3Dosage of
Yield of
Example 2-1
DMA
1.1mmol
87％
Examples 2 to 2
DMSO
1mmol
36％
Examples 2 to 3
DMF
1mmol
78％
Examples 2 to 4
NMP
1mmol
77％
Examples 2 to 5
CH2Cl2
1mmol
0％
And (3) analysis: comparison shows that under the same conditions, DMA is used as a solvent to obtain the highest product yield and is cheap.
Example 3
The influence and effect of different reactant ratios on the reaction are examined: magnetons, 1-phenylpyrrolidine (x mmol), terephthalonitrile (0.5mmol) and Cs were sequentially added to a 20mL reaction tube2CO3(y mmol) and a different solvent (5mL) were reacted at ambient temperature under blue light irradiation for 16 hours. Extracting the reaction liquid with ethyl acetate, rotary evaporating, separating by column chromatography, removing the solvent by rotary evaporation, and pumping the reaction liquid by a vacuum oil pump to obtain the target product. The product yields were calculated by weighing and are shown in table 3.
TABLE 3
And (3) analysis: comparison shows that the tertiary amine terephthalonitrile Cs is used under otherwise identical conditions2CO3The ratio of (A) to (B) is 2:1:2, the product obtained is high in yield and low in cost.
Example 4
Magnetons, 1- (3, 5-dimethylphenyl) pyrrolidine (1mmol), terephthalonitrile (0.5mmol) and Cs were sequentially added to a 20mL reaction tube2CO3(1mmol) and N, N-dimethylacetamide (5mL) were reacted at room temperature under blue light irradiation for 15 hours. Extracting the reaction liquid by ethyl acetate, carrying out rotary evaporation, carrying out column chromatography separation, removing the solvent by rotary evaporation, and carrying out vacuum oil pump pumping to obtain the target product with the yield of 60%. Product structure warp1H-NMR and13C-NMR was carried out to determine,1H-NMR and13C-NMR data are as follows:
1H NMR(400MHz,CDCl3)δppm 7.70(d,J＝7.6Hz,1H),7.47(ddd,J＝8.0,8.0,1.2Hz,1H),7.35-7.30(m,2H),6.37(s,1H),6.09(s,2H),5.04(dd,J＝8.8,2.0Hz,1H),3.79-3.74(m,1H),3.47-3.41(m,1H),2.57-2.51(m,1H),2.21(s,6H),2.05-1.97(m,3H).
13C NMR(100MHz,CDCl3)δppm 149.3,146.7,138.7,133.6,133.0,127.2,126.9,118.8,117.8,110.5(×2),110.0,61.5,49.5,35.3,23.2,21.7.
the structural formula of the product is as follows:
example 5
A20 mL reaction tube was sequentially charged with magneton, 1- (3-bromophenyl) pyrrolidine (1mmol), terephthalonitrile (0.5mmol), and Cs2CO3(1mmol) and N, N-dimethylacetamide (5mL) were reacted at room temperature under blue light irradiation for 40 hours. Extracting the reaction liquid with ethyl acetate, rotary evaporating, separating by column chromatography, removing the solvent by rotary evaporation, and pumping by a vacuum oil pump to obtain the target product with the yield of 50%. Product structure warp1H-NMR and13C-NMR was carried out to determine,1H-NMR and13C-NMR data are as follows:
1H NMR(400MHz,CDCl3)δppm 7.59(d,J＝8.4Hz,2H),7.31(d,J＝8.4Hz,2H),6.96(dd,J＝8.0,8.0Hz,1H),6.78(dd,J＝7.6,0.8Hz,1H),6.62(dd,J＝2.0,2.0Hz,1H),6.30(dd,J＝8.0,2.0Hz,1H),4.74(dd,J＝8.8,2.0Hz,1H),3.72-3.67(m,1H),3.42-3.38(m,1H),2.48-2.40(m,1H),2.06-1.89(m,3H).
13C NMR(100MHz,CDCl3)δppm 149.6,147.9,132.6(×2),130.4,126.7(×2),123.3,119.3,118.9,115.1,111.2,110.8,62.7,49.3,35.9,23.0.
the structural formula of the product is as follows:
example 6
Magnetons, 1- (3-chlorophenyl) pyrrolidine (1mmol), terephthalonitrile (0.5mmol), and Cs were sequentially added to a 20mL reaction tube2CO3(1mmol) and N, N-dimethylacetamide (5mL) were reacted at room temperature under blue light irradiation for 40 hours. Extracting the reaction solution with ethyl acetate, rotary evaporating, separating by column chromatography, rotary evaporating to remove solvent, vacuum oil pumping to obtain target product with yield of 54%, and purifying by vacuum oil pump1H-NMR and13C-NMR was carried out to determine,1H-NMR and13C-NMR data are as follows:
1H NMR(400MHz,CDCl3)δppm 7.59(d,J＝8.4Hz,2H),7.31(d,J＝8.0Hz,2H),7.03(dd,J＝8.0,8.0Hz,1H),6.64(dd,J＝7.2,1.2Hz,1H),6.45(dd,J＝2.4,2.0Hz,1H),6.27(dd,J＝8.0,2.0Hz,1H),4.74(dd,J＝8.8,2.4Hz,1H),3.73-3.68(m,1H),3.45-3.38(m,1H),2.50-2.41(m,1H),2.05-2.02(m,2H),1.95-1.89(m,1H).
13C NMR(100MHz,CDCl3)δppm 149.7,147.7,135.0,132.6(×2),130.1,126.7(×2),118.9,116.4,112.3,110.8,62.7,49.3,35.8,23.0.
the structural formula of the product is as follows:
example 7
Magnetons, 1- (3, 5-dimethylphenyl) pyrrolidine (1mmol), phthalodinitrile (0.5mmol), and Cs were sequentially added to a 20mL reaction tube2CO3(1mmol) and N, N-dimethylacetamide (5mL) were reacted at room temperature under blue light irradiation for 40 hours. Extracting the reaction solution with ethyl acetate, rotary evaporating, separating by column chromatography, rotary evaporating to remove solvent, vacuum oil pumping to obtain the target product with yield of 51%, and purifying by using a product structure1H-NMR and13C-NMR was carried out to determine,1H-NMR and13C-NMR data are as follows:
1H NMR(400MHz,CDCl3)δppm 7.70(d,J＝7.6Hz,1H),7.47(ddd,J＝8.0,8.0,1.2Hz,1H),7.35-7.30(m,2H),6.37(s,1H),6.09(s,2H),5.04(dd,J＝8.8,2.0Hz,1H),3.79-3.74(m,1H),3.47-3.41(m,1H),2.57-2.51(m,1H),2.21(s,6H),2.05-1.97(m,3H).
13C NMR(100MHz,CDCl3)δppm 149.3,146.7,138.7,133.6,133.0,127.2,126.9,118.8,117.8,110.5(×2),110.0,61.5,49.5,35.3,23.2,21.7.
the structural formula of the product is as follows:
example 8
Magnetons, 1-phenylpyrrolidine (1mmol), isophthalonitrile (0.5mmol) and Cs were sequentially added to a 20mL reaction tube2CO3(1mmol) and N, N-dimethylacetamide (5mL) were reacted at room temperature under blue light irradiation for 40 hours. Extracting the reaction solution with ethyl acetate, rotary evaporating, separating by column chromatography, rotary evaporating to remove solvent, vacuum oil pumping to obtain target product with yield of 48%, and purifying by vacuum oil pump1H-NMR and13C-NMR was carried out to determine,1H-NMR and13C-NMR data are as follows:
1H NMR(400MHz,CDCl3)δppm 7.56-7.50(m,3H),7.44(d,J＝7.6Hz,1H),7.21-7.17(m,2H),6.72(dd,J＝7.6,7.2Hz,1H),6.49(d,J＝7.6Hz,2H),4.76(dd,J＝8.4,2.0Hz,1H),3.80-3.75(m,1H),3.48-3.42(m,1H),2.50-2.41(m,1H),2.07-2.00(m,2H),1.95-1.91(m,1H).
13C NMR(100MHz,CDCl3)δppm 146.7,146.5,130.6(×2),129.7,129.4,129.2(×2),119.1,116.6,112.6(×2),112.5,62.5,49.3,36.0,23.1.
the structural formula of the product is as follows:
example 9
A20 mL reaction tube was charged with magneton, 1-phenylazepane (1mmol), and terephthalonitrile (N-phenylazepane:) ((N-phenylazepane))0.5mmol)、Cs2CO3(1mmol) and N, N-dimethylacetamide (5mL) were reacted at room temperature under blue light irradiation for 15 hours. Extracting the reaction liquid by ethyl acetate, carrying out rotary evaporation, carrying out column chromatography separation, removing the solvent by rotary evaporation, and carrying out vacuum oil pump pumping to obtain the target product with the yield of 60%. Product structure warp1H-NMR and13C-NMR was carried out to determine,1H-NMR and13C-NMR data are as follows:
1H NMR(400MHz,CDCl3)δ7.63(d,J＝8.4Hz,2H),7.36(d,J＝8.4Hz,2H),7.20(dd,J＝7.2,7.2,0.8Hz,2H),6.70(dd,J＝7.2,7.2Hz,1H),6.61(d,J＝8.0Hz,2H),4.68(dd,J＝12.0,6.0Hz,1H),3.91(dd,J＝17.6,4.0Hz,1H),3.56-3.49(m,1H),2.52-2.45(m,1H),2.03-1.73(m,5H),1.58-1.48(m,1H),1.46-1.30(m,1H)
13C NMR(100MHz,CDCl3)δ150.2,148.5,132.7(×2),129.3(×2),126.7(×2),119.0,116.1,111.4(×2),110.5,63.0,45.3,38.2,29.6,28.3,26.6.
the structural formula of the product is as follows:
example 10
Magnetons, 1- (naphthalen-2-yl) pyrrolidine (1mmol), terephthalonitrile (0.5mmol), and Cs were sequentially added to a 20mL reaction tube2CO3(1mmol) and N, N-dimethylacetamide (5mL) were reacted at room temperature under blue light irradiation for 15 hours. Extracting the reaction solution with ethyl acetate, rotary evaporating, separating by column chromatography, rotary evaporating to remove solvent, vacuum oil pumping to obtain target product with yield of 55%, and purifying by vacuum oil pump1H-NMR and13C-NMR was carried out to determine,1H-NMR and13C-NMR data are as follows:
1H NMR(400MHz,CDCl3)δppm 7.67-7.56(m,5H),7.37(d,J＝8.0Hz,2H),7.37-7.33(m,1H),7.21-7.17(m,1H),6.82(dd,J＝9.2,2.8Hz,1H),6.70(d,J＝2.4Hz,1H),4.90(dd,J＝8.8,2.0Hz,1H),3.88-3.83(m,1H),3.59-3.53(m,1H),2.55-2.45(m,1H),2.10-1.94(m,3H).
13C NMR(100MHz,CDCl3)δppm 150.4,144.5,134.9,132.5(×2),128.9,127.6,126.8(×2),126.6,126.4,126.0,121.9,119.0,115.9,110.7,106.0,62.8,49.4,36.0,23.2.
the structural formula of the product is as follows:
example 11
Magnetons, 4-phenylmorpholine (1mmol), terephthalonitrile (0.5mmol) and Cs were added in this order to a 20mL reaction tube2CO3(1mmol) and N, N-dimethylacetamide (5mL) were reacted at room temperature under blue light irradiation for 15 hours. Extracting the reaction solution with ethyl acetate, rotary evaporating, separating by column chromatography, rotary evaporating to remove solvent, vacuum oil pumping to obtain target product with yield of 30%, and purifying by vacuum oil pump1H-NMR and13C-NMR was carried out to determine,1H-NMR and13C-NMR data are as follows:
1H NMR(400MHz,CDCl3)δppm 7.49(d,J＝8.4Hz,2H),7.43(d,J＝8.4Hz,2H),7.16(dd,J＝8.8,8.8Hz,2H),6.89(d,J＝7.6Hz,2H),6.88(dd,J＝7.6,7.6Hz,1H),4.44-4.41(m,1H),3.98-3.94(m,3H),3.65-3.60(m,1H),3.42(dt,J＝12.4,3.6Hz,1H),3.15-3.09(m,1H).
13C NMR(100MHz,CDCl3)δppm 150.4,144.9,132.2(×2),129.0(×2),128.6(×2),122.4,121.1(×2),118.7,111.1,72.6,67.6,61.4,52.6.
the structural formula of the product is as follows:
example 12
Magnetons, N-dimethylaniline (1mmol), terephthalonitrile (0.5mmol) and Cs were sequentially added to a 20mL reaction tube2CO3(1mmol) and N, N-dimethylacetamide (5mL) were reacted at room temperature under blue light irradiation for 15 hours. Extracting the reaction liquid with ethyl acetate, rotary steaming, separating by column chromatography,removing solvent by rotary evaporation, and vacuum oil pumping to obtain target product with yield of 43%, and product structure1H-NMR and13C-NMR was carried out to determine,1H-NMR and13C-NMR data are as follows:
1H NMR(400MHz,CDCl3)δ7.64(d,J＝8.0Hz,2H),7.39(d,J＝7.6Hz,2H),7.28(dd,J＝8.0,8.0Hz,2H),6.80(dd,J＝7.2,7.2Hz,1H),6.75(d,J＝8.4Hz,2H),4.62(s,2H),3.09(s,3H).
13C NMR(100MHz,CDCl3)δ149.2,145.0,132.5(×2),129.4(×2),127.4(×2),118.9,117.3,112.5(×2),110.8,56.7,38.9.
the structural formula of the product is as follows:
example 13
Magnetons, 1-phenylpyrrolidine (1mmol), phthalodinitrile (0.5mmol) and Cs were added in this order to a 20mL reaction tube2CO3(1mmol) and N, N-dimethylacetamide (5mL) were reacted at room temperature under blue light irradiation for 40 hours. Extracting the reaction solution with ethyl acetate, rotary evaporating, separating by column chromatography, rotary evaporating to remove solvent, vacuum oil pumping to obtain target product with yield of 48%, and purifying by vacuum oil pump1H-NMR and13C-NMR was carried out to determine,1H-NMR and13C-NMR data are as follows:
1H NMR(400MHz,CDCl3)δppm 7.70(dd,J＝7.6,0.8Hz,1H),7.47(ddd,J＝7.6,7.6,1.6Hz,1H),7.34-7.29(m,2H),7.18-7.14(m,2H),6.68(dd,J＝7.6,7.6Hz,1H),6.44(d,J＝8.0Hz,2H),5.05(dd,J＝10.0,2.0Hz,1H),3.81-3.76(m,1H),3.49-3.43(m,1H),2.63-2.53(m,1H),2.09-1.98(m,3H)
13C NMR(100MHz,CDCl3)δppm 149.0,146.5,133.6,133.0,129.1(×2),127.3,126.8,117.7,116.6,112.5(×2),110.1,61.5,49.4,35.3,23.3.
the structural formula of the product is as follows:
example 14
Magnetons, 1-phenylpyrrolidine (1mmol), methyl p-cyanobenzoate (0.5mmol) and Cs were sequentially added to a 20mL reaction tube2CO3(1mmol) and N, N-dimethylacetamide (5mL) were reacted at room temperature under blue light irradiation for 15 hours. Extracting the reaction solution with ethyl acetate, rotary evaporating, separating by column chromatography, rotary evaporating to remove solvent, vacuum oil pumping to obtain the target product with yield of 11%, and purifying by vacuum oil pump1H-NMR and13C-NMR was carried out to determine,1H-NMR and13C-NMR data are as follows:
1H NMR(400MHz,CDCl3)δppm 7.97(d,J＝8.0Hz,2H),7.31(d,J＝8.0Hz,2H),7.17–7.12(m,2H),6.66(t,J＝8.0Hz,1H),6.47(d,J＝8.0Hz,2H),4.75(dd,J＝8.4,2.4Hz,1H),3.90(s,3H),3.76-3.71(m,1H),3.43(q,J＝8.0Hz,1H),2.45-2.38(m,1H),2.05-1.96(m,2H),1.95-1.92(m,1H)
13C NMR(100MHz,CDCl3)δppm 167.0,150.2,146.9,129.9(×2),129.1(×2),128.7,126.0(×2),116.2,112.4(×2),62.9,52.0,49.2,35.9,23.2.
the structural formula of the product is as follows:
the above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.