CN116715628B - A method for synthesizing quinoline-substituted homoallylamine compounds - Google Patents
A method for synthesizing quinoline-substituted homoallylamine compoundsInfo
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
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Abstract
The invention discloses a method for synthesizing quinoline-substituted homoallylamine compounds, which takes 2-allylquinoline as an allylation reagent, realizes allylation of the latter by a method of cross coupling of 2-allylquinoline and N-aryl imine in the presence of a catalyst, alkali and a solvent, and the system is placed in an air atmosphere at room temperature to be stirred and reacted for 6 hours to obtain higher product yield, so as to synthesize quinoline-substituted homoallylamine compounds. The method does not need to introduce metal, has mild reaction conditions, simple and convenient operation, good functional group compatibility and rapid reaction, and is an excellent strategy for synthesizing quinoline-substituted homoallylamine compounds.
Description
Technical Field
The invention belongs to the technical field of synthesis and application of organic compounds, and particularly relates to a synthesis method of quinoline-substituted homoallylamine compounds.
Background
The research on the homoallylamine compounds has been reported, the compounds can synthesize various medicines and natural substances with biological activity, the synthetic route is very important, and the allylation of the N-aryl imine is a relatively direct and efficient strategy for synthesizing the homoallylamine compounds because of the relatively high reactivity of the N-aryl imine and stable preservation. However, allylation has been a difficult research topic in the field of organic synthesis, reports of allylation of N-aryl imine are very rare, and most of allylation metal reagents and imine coupling reactions, three-component reactions involving 1, 3-butadiene and the like have the defects of environment friendliness, poor functional group tolerance, high cost of added raw materials and the like. Therefore, it is of great importance to develop a milder allylation process for N-aryl imines.
There have been some reports of allylation of N-aryl imines, but these methods have some drawbacks and disadvantages. For example, 1999 journal of organic chemistry (J.Org.chem.1999, 64,4233.) reported a cross-coupling reaction of allylic silicon reagent with N-aryl imine using tetrabutylammonium fluoride as a catalyst, adding a small amount of molecular sieve to the system, the reaction could yield higher product yields and the range of substrate use was wider, but the nucleophile used for the reaction needed to be prepared and used with exclusion of air, the operation was not simple enough, the inhibition was also larger in large scale reactions, the practicality was not high, 2017 "society of American chemistry (J.am.chem.Soc.2017, 139, 4362.) reported a cross-coupling reaction of allylic benzene with N-aryl imine promoted by sodium bis-trimethylsilylamide, the reaction was in the solvent of dioxane, the system used was not mild enough to yield 96% of product at room temperature, the system needed to add sodium bis-trimethylsilylamide, the range of substrate had not been well tolerated in the system, the range of acidic functionalities was also high enough to be used, the metal bromide chemistry was not expensive to be used to afford a metal bromide chemistry (J.am.chem.society of chemical society), and the metal chemistry was also reported a higher cost of metal bromide chemistry was higher than that was reported by chem.142, and a metal chemistry was higher than practical for the reduction of metal imine.
Not only can the bi-component cross-coupling reaction realize the allylation of the N-aryl imine, but also part of the three-component reaction participated by the 1, 3-butadiene can realize the conversion. Both organic flash report (org. Lett.2007,9,1871) and organometals (Organometallics) describe allylation reactions involving aryl nucleophiles using diphenylzinc reagent as nucleophile, a combination of Ni (acac) 2 and 3-hexene as reaction catalyst, THF as solvent, and a system stirred for three hours at 30 ℃ to achieve good yields, and a combination of Ni (cod) 2 and 3-hexyne as nucleophile, the same reaction stirred for 6 hours at ambient temperature to yield nearly 100% yields, and the system has a wide substrate range and practical value. However, both reactions need to use metallic nickel catalysis and anhydrous and anaerobic reaction conditions and atmosphere, the operation is not simple enough, and metallic catalysts are also needed, so that the cost is high, the wide application is not facilitated, and the method is not a good way for synthesizing the high allylamine compounds. Therefore, the method for allylating the N-aryl imine has the advantages of easily available raw materials, good selectivity, wide application range and high safety and reliability.
In summary, a more stable and easy-to-prepare allylation reagent is selected, a mild method for cross-coupling the allylation reagent with N-aryl imine is developed to synthesize the high allylation compound, the yield, the rate, the functional group tolerance, the economy and the operability of the reaction are further improved, and the method has important significance.
Disclosure of Invention
As mentioned above, although there are many methods for allylating N-arylimines, each method has its limitations. Aiming at the defects of the prior art, the invention provides a synthesis method of quinoline-substituted homoallylamine compounds, and allylation of the quinoline-substituted homoallylamine compounds is realized by a cross coupling method of 2-allylquinoline and N-aryl imine. The invention takes cheap and easily available 2-allylquinoline as allylation reagent, promotes the coupling reaction of boron trifluoride diethyl etherate and triethylamine, and obtains the corresponding allylation product with excellent yield by the reaction under the conditions of room temperature and air. The method has the advantages of mild reaction conditions, simple operation and good functional group tolerance, and is an excellent scheme for synthesizing various homoallylamine compounds.
According to the synthesis method of the quinoline substituted homoallylamine compound, allylquinoline and allylquinoline with partial substituents are used as allylation reagents, allylation of the allylation reagent is realized by a method of cross coupling of 2-allylquinoline and N-aryl imine in the presence of a catalyst, alkali and a solvent, and the system is placed in an air atmosphere at room temperature to react for 6 hours under stirring, so that higher product yield can be obtained, and the quinoline substituted homoallylamine compound is synthesized.
The substituent in the allyl quinoline with partial substituent is selected from one of hydrogen, methoxy, phenoxy, methyl, hydroxyl, fluorine, chlorine, bromine, nitro, trifluoromethyl and the like.
The N-aryl imine is selected from N-p-methoxyphenyl aryl imine, N-p-tolyl aryl imine, N-phenyl p-methoxyphenyl imine, N-phenyl p-tolyl imine, N-phenyl p-chlorophenyl imine, N-phenyl p-bromophenyl imine and the like, and the structural general formula is shown as follows:
In the general formula, R 1、R2 is independently selected from one of hydrogen, methoxy, phenoxy, methyl, hydroxyl, fluorine, chlorine, bromine, nitro and trifluoromethyl.
The solvent is selected from dichloroethane, toluene, methanol, etc., preferably methanol.
The catalyst is boron trifluoride diethyl ether or ferric chloride, preferably boron trifluoride diethyl ether.
The base is selected from sodium methoxide, sodium tert-butoxide, triethylamine, etc., preferably triethylamine.
In the invention, the molar ratio of the N-aryl imine to the allyl quinoline to the catalyst to the alkali is 1.0:2.0-2.5:0.5:0.5, and the preferable molar ratio is 1.0:2.0:0.5:0.5.
The reaction route of the invention is schematically shown as follows:
R 1、R2、R3 is independently selected from one of hydrogen, methoxy, phenoxy, methyl, hydroxyl, fluorine, chlorine, bromine, nitro and trifluoromethyl.
In the invention, nucleophilic raw materials are prepared by adopting the most common coupling method, namely, allylmagnesium bromide and 2-bromoquinoline are used for cross coupling under the protection of nitrogen, namely, 5.0mmol of 2-bromoquinoline and derivatives thereof are firstly added into a Schlenk bottle under the protection of nitrogen, 10.0ml of LTHF is added as a reaction solvent, allylmagnesium bromide (7.5 mmol) is added, the reaction is stirred for 4 hours, then water is added dropwise for quenching, and finally, the raw materials allylquinoline (eluent: petroleum ether/ethyl acetate=20/1, V/V) is obtained through column chromatography separation and purification.
Preparation of 6-Methoxyallylquinoline, 4, 8-dimethylallylquinoline by adding 2-chloroquinoline (81.8 mg,5.0 mmol) with substituents to a Schlenk flask under nitrogen protection, adding 10mol% Co (acac) 2 (89.0 mg,0.25 mmol), adding 10.0mL tetrahydrofuran, adding allylmagnesium bromide (7.5 mmol), stirring the reaction for 4 hours, quenching the reaction mixture dropwise with water, and separating and purifying the organic phase by column chromatography to give the starting allylquinoline (eluent: petroleum ether/ethyl acetate=20/1, V/V). Chemical rapid report (chem. Lett.2004,33,1240.)
The N-aryl imine has high reaction activity due to the fact that the molecular structure of the N-aryl imine contains special carbon-nitrogen double bonds, the N-benzyl aniline is an electrophilic raw material which can exist stably in amine compounds and has high reaction activity, but the N-benzyl aniline can be directly purchased, the imine derivative with substituent groups on the diphenyl of the N-benzyl aniline needs to be self-made, the preparation method is simple, only 1 equivalent of aryl formaldehyde and 1.2 equivalent of aniline compounds are needed to be added into a flask at room temperature, a small amount of magnesium chloride and molecular sieves are added into the system, 10mL of methanol is added and the mixture is slightly heated and refluxed, after the reaction is stopped, suction filtration is carried out, and filtrate is cooled, concentrated and recrystallized to obtain the target product.
In the invention, the methanol can complete the reaction without dehydration and purification by putting the system in the air at normal temperature.
The invention relates to a reaction method for allylating N-aryl imine, which comprises the following specific preparation processes:
N-arylimine (18.0 mg,0.1 mmol) was weighed into a10 mL round bottom flask equipped with a stirrer, triethylamine (7.0. Mu.L, 0.05 mmol), boron trifluoride diethyl ether (7.1 mg,0.05 mmol) and 3mL methanol were added respectively, allylquinoline (33.8 mg,0.2 mmol) was added under stirring, stirred at room temperature for 6 hours, concentrated in vacuo, and then purified by silica gel column chromatography and preparative thin layer chromatography (eluent: petroleum ether/ethyl acetate=5/1, V/V) to give the corresponding product.
Compared with the existing reaction method for allylating the N-aryl imine, the method has the following advantages:
1. The method has the advantages of mild reaction conditions, excellent 2 and yield, simple and rapid 3 and environment-friendly system, and 5 has wide application range of reaction substrates, and 6 provides an excellent scheme for synthesizing quinoline substituted homoallylamine compounds.
Detailed Description
The technical scheme of the invention is further analyzed and described below by combining specific examples.
Example 1:
N-benzylidene aniline (18.0 mg,0.1 mmol) was weighed into a 10mL round bottom flask equipped with a stirrer, triethylamine (7.0. Mu.L, 0.05 mmol), boron trifluoride etherate (7.1 mg,0.05 mmol) and 3mL methanol were added separately. 2-allylquinoline (33.8 mg,0.2 mmol) was added with stirring and stirred at room temperature for 6 hours. Vacuum concentrating, separating and purifying with silica gel column chromatography and preparative thin layer chromatography (eluent: petroleum ether/ethyl acetate=5/1) to obtain the product.
1H NMR(400MHz,CDCl3)δ8.07(dd,J＝13.0,8.5Hz,2H),7.77(d,J＝8.1Hz,1H),7.74(t,1H),7.55–7.47(m,2H),7.43(d,J＝7.1Hz,2H),7.36(t,J＝7.5Hz,2H),7.31–7.23(m,1H),7.08(t,J＝7.7Hz,2H),6.89(d,J＝15.9Hz,1H),6.80–6.70(m,1H),6.69–6.62(m,1H),6.53(d,J＝8.0Hz,2H),4.58(dd,J＝8.2,5.0Hz,1H),4.23(t,J＝6.5Hz,1H),2.94–2.85(m,1H),2.85–2.74(m,1H).13C NMR(101MHz,CDCl3)δ155.70,148.01,147.21,143.38,136.58,134.34,133.15,129.90,129.21,129.18,128.87,127.62,127.41,127.32,126.41,126.36,118.73,117.56,113.60,57.51,42.64.HRMS(ESI):m/z 351.1861[M+H]+,calcd.for C25H23N2351.1861.
The reaction condition optimization process is as follows:
Example 2:
experimental procedure reference example 1, petroleum ether/ethyl acetate mixed solvent as eluent (v: v=5:1), product yield 87%, tan liquid.
1H NMR(400MHz,CDCl3)δ8.06(dd,J＝11.6,8.5Hz,2H),7.77(d,J＝8.1,1.4Hz,1H),7.72–7.67(m,1H),7.54–7.46(m,2H),7.34(d,2H),7.09(t,2H),6.95–6.82(m,3H),6.79–6.61(m,2H),6.53(d,2H),4.54(dd,J＝7.9,5.3Hz,1H),3.80(s,3H),2.90–2.82(m,1H),2.82–2.73(m,1H).13C NMR(101MHz,CDCl3)δ158.80,155.77,148.02,147.29,136.55,135.33,134.24,133.28,129.88,129.20,127.61,127.48,127.41,126.33,118.72,117.52,114.22,113.64,56.96,55.37,42.66.HRMS(ESI):m/z 381.1961[M+H]+,calcd.for C31H27N2O 381.1967.
Example 3:
Experimental procedure reference example 1, petroleum ether/ethyl acetate mixed solvent as eluent (v: v=5:1), product yield 90%, yellow liquid.
1H NMR(400MHz,CDCl3)δ7.98(dd,J＝13.7,8.5Hz,2H),7.70(d,J＝8.1,1.4Hz,1H),7.66–7.57(m,3H),7.47–7.35(m,2H),7.27–7.15(m,3H),7.10(d,2H),7.06–6.94(m,4H),6.89(d,2H),6.84–6.73(m,2H),6.71–6.54(m,2H),6.44(d,2H),4.47(dd,J＝8.0,5.1Hz,2H),2.85–2.76(m,1H),2.71(dt,J＝14.8,7.7Hz,1H).13C NMR(101MHz,CDCl3)δ157.60,157.26,155.65,148.09,147.04,145.72,136.56,134.51,132.75,130.23,129.90,129.84,129.26,129.22,127.62,127.44,126.38,123.26,121.35,118.82,118.79,117.72,117.05,113.70,57.38,42.46.HRMS(ESI):m/z 443.2125[M+H]+,calcd.for C31H27N2O 443.2123.
Example 4:
Experimental procedure reference example 1, petroleum ether/ethyl acetate mixed solvent as eluent (v: v=5:1), product yield 94%, yellow liquid.
1H NMR(400MHz,CDCl3)δ8.08(d,J＝8.6Hz,1H),8.04(d,J＝8.5Hz,1H),7.77(d,J＝8.1Hz,1H),7.69(t,J＝8.6,6.8,1.5Hz,1H),7.57–7.44(m,2H),7.31(d,J＝7.8Hz,2H),7.16(d,J＝7.7Hz,2H),7.07(t,2H),6.88(d,J＝16.0Hz,1H),6.80–6.69(m,1H),6.64(t,J＝7.4Hz,1H),6.52(d,J＝8.0Hz,2H),4.55(dd,J＝8.1,5.2Hz,1H),2.92–2.83(m,1H),2.83–2.73(m,1H),2.34(s,3H).13C NMR(126MHz,CDCl3)δ155.76,147.99,147.30,140.34,136.88,136.59,134.24,133.37,129.91,129.56,129.21,129.18,127.62,127.41,126.36,126.32,118.72,117.50,113.59,57.25,42.67,21.24.HRMS(ESI):m/z 365.2013[M+H]+,calcd.for C26H25N2365.2018.
Example 5:
Experimental procedure reference example 1, petroleum ether/ethyl acetate mixed solvent as eluent (v: v=5:1), product yield 94%, yellow liquid.
1H NMR(400MHz,CDCl3)δ8.11(d,J＝8.5Hz,1H),8.06(d,J＝8.5Hz,1H),7.78(d,J＝8.1Hz,1H),7.74–7.68(m,1H),7.61(d,J＝8.1Hz,2H),7.55(d,J＝8.1Hz,2H),7.51(t,J＝7.5Hz,2H),7.15–7.03(m,2H),6.90(d,J＝15.9Hz,1H),6.78–6.70(m,1H),6.67(t,J＝7.3Hz,1H),6.48(d,J＝7.5Hz,2H),4.63(dd,J＝8.2,4.9Hz,1H),2.95–2.85(m,1H),2.83–2.73(m,1H).13C NMR(101MHz,CDCl3)δ155.42,148.09,147.69,146.78,136.67,134.88,132.10,129.97,129.31,129.30(q,J＝32.01Hz)129.27,127.65,127.50,126.80,126.47,125.92(q,J＝4.2Hz),124.31(q,J＝271.87Hz),118.85,118.04,113.65,57.26,42.44.19F NMR(376MHz,CDCl3)δ-62.06.HRMS(ESI):m/z 419.1732[M+H]+,calcd.for C26H22F3N2419.1730.
Example 6:
Experimental procedure reference example 1, petroleum ether/ethyl acetate mixed solvent as eluent (v: v=5:1), product yield 85%, yellowish white liquid.
1H NMR(400MHz,CDCl3)δ8.25–8.19(m,2H),8.10(d,J＝8.6Hz,1H),8.03(d,J＝8.5Hz,1H),7.78(d,1H),7.73–7.67(m,1H),7.61(dd,J＝8.7,1.5Hz,2H),7.55–7.45(m,2H),7.12–7.05(m,2H),6.88(d,J＝15.6Hz,1H),6.77–6.65(m,2H),6.45(d,2H),4.66(dd,J＝8.2,5.1Hz,1H),4.31(brs,1H),2.95–2.85(m,1H),2.84–2.73(m,1H).13C NMR(101MHz,CDCl3)δ155.19,151.33,148.10,147.40,146.47,136.72,135.19,131.42,130.01,129.37,129.28,127.66,127.53,127.36,126.54,124.27,118.91,118.34,113.66,57.24,42.22.HRMS(ESI):m/z 396.1700[M+H]+,calcd.for C25H22N3O2396.1712.
Example 7:
experimental procedure reference example 1, petroleum ether/ethyl acetate mixed solvent as eluent (v: v=5:1), product yield 93%, yellow liquid.
1H NMR(400MHz,CDCl3)δ8.09(d,J＝8.6Hz,1H),8.05(d,J＝8.5Hz,1H),7.77(d,J＝8.2,1.5Hz,1H),7.73–7.66(m,1H),7.54–7.46(m,2H),7.43–7.34(m,2H),7.09(dd,J＝8.6,7.3Hz,2H),7.04(t,J＝8.7Hz,2H),6.87(d,1H),6.78–6.63(m,2H),6.51(d,J＝7.0,1.5Hz,2H),4.56(dd,J＝8.1,5.1Hz,1H),2.90–2.81(m,1H),2.81–2.71(m,1H).13C NMR(101MHz,CDCl3)δ162.07(d,J＝244.4Hz),155.57,148.03,147.03,139.04(d,J＝2.9Hz),136.64,134.52,132.72,129.95,129.25,129.22,127.94(d,J＝8.0Hz),127.63,127.46,126.42,118.79,117.80,115.72(d,J＝21.3Hz),113.67,56.95,42.69.19F NMR(376MHz,CDCl3)δ-115.70.HRMS(ESI):m/z 367.1769[M+H]+,calcd.for C25H22FN2369.1767.
Example 8:
Experimental procedure reference example 1, petroleum ether/ethyl acetate mixed solvent as eluent (v: v=5:1), product yield 85%, white liquid.
1H NMR(500MHz,CDCl3)δ8.09(d,J＝8.5Hz,1H),8.04(d,J＝8.5Hz,1H),7.77(d,J＝8.1Hz,1H),7.70(t,J＝7.7Hz,1H),7.56–7.45(m,2H),7.40–7.34(m,2H),7.34–7.29(m,2H),7.08(t,J＝7.7Hz,2H),6.87(d,J＝15.9Hz,1H),6.77–6.62(m,2H),6.49(d,J＝8.0Hz,2H),4.55(dd,J＝8.1,5.0Hz,1H),4.26(brs,1H),2.90–2.81(m,1H),2.81–2.71(m,1H).13C NMR(101MHz,CDCl3)δ155.53,148.09,146.93,141.97,136.62,134.69,132.91,132.43,129.93,129.27,129.05,127.84,127.63,127.47,126.42,118.81,117.88,113.66,57.01,42.53.HRMS(ESI):m/z 385.1466[M+H]+,calcd.for C25H22ClN2385.1472.
Example 9:
experimental procedure reference example 1, petroleum ether/ethyl acetate mixed solvent as eluent (v: v=5:1), product yield 86%, yellow liquid.
1H NMR(400MHz,CDCl3)δ8.09(d,J＝8.6Hz,1H),8.04(d,J＝8.5Hz,1H),7.77(dd,J＝8.0,1.4Hz,1H),7.73–7.67(m,1H),7.54–7.42(m,4H),7.31(d,2H),7.12–7.03(m,2H),6.87(d,J＝16.0Hz,1H),6.77–6.59(m,2H),6.48(d,2H),4.53(dd,J＝8.0,5.1Hz,1H),4.23(brs,1H),2.90–2.81(m,1H),2.81–2.71(m,1H)13C NMR(101MHz,CDCl3)δ155.52,148.10,146.90,142.53,136.62,134.72,132.39,132.00,129.94,129.27,128.24,127.64,127.48,126.43,121.01,118.82,117.91,113.67,57.07,42.48.HRMS(ESI):m/z 429.0965[M+H]+,calcd.for C25H22BrN2429.0966.
Example 10:
Experimental procedure reference example 1, petroleum ether/ethyl acetate mixed solvent as eluent (v: v=5:1), product yield 74%, off-white liquid.
1H NMR(400MHz,CDCl3)δ8.08(d,J＝8.6Hz,1H),8.05(d,J＝8.6Hz,1H),7.77(d,J＝6.7Hz,1H),7.73–7.66(m,1H),7.55–7.47(m,2H),7.42(d,J＝6.8Hz,2H),7.35(t,J＝7.6Hz,2H),7.30–7.27(m,0H),6.88(d,J＝16.2Hz,1H),6.79–6.73(m,1H),6.69–6.64(m,2H),6.47(d,J＝8.9Hz,2H),4.54–4.45(m,1H),3.68(s,3H),2.92–2.72(m,2H).13C NMR(101MHz,CDCl3)δ155.77,152.12,147.99,143.67,141.50,136.61,134.22,133.40,129.92,129.15,128.85,127.62,127.43,127.28,126.49,126.36,118.76,114.84,58.33,55.84,42.72.HRMS(ESI):m/z 381.1957[M+H]+,calcd.for C26H25N2O 381.1967.
Example 11:
Experimental procedure reference example 1, petroleum ether/ethyl acetate mixed solvent as eluent (v: v=1:1), product yield 72%, yellow brown solid.
1H NMR(400MHz,CDCl3)δ8.09(d,J＝8.5Hz,2H),7.76(dd,J＝8.1Hz,1H),7.66(td,1H),7.52–7.45(m,2H),7.39–7.34(m,2H),7.31(t,J＝7.5Hz,2H),7.23(t,J＝7.1Hz,1H),6.87(d,J＝16.2Hz,1H),6.77–6.66(m,1H),6.61(d,J＝8.9Hz,2H),6.33(d,J＝8.8Hz,2H),4.40(dd,J＝8.0,5.0Hz,1H),2.84–2.75(m,1H),2.75–2.65(m,1H).13C NMR(101MHz,CDCl3)δ155.70,148.48,147.55,143.73,140.99,137.05,134.12,133.67,130.20,128.78,128.63,127.62,127.43,127.19,126.49,118.92,116.29,115.15,58.29,42.66.HRMS(ESI):m/z 389.1632[M+Na]+,calcd.for C25H22N2ONa 389.1630.
Example 12:
Experimental procedure reference example 1, petroleum ether/ethyl acetate mixed solvent as eluent (v: v=5:1), product yield 83%, yellow liquid.
1H NMR(400MHz,CDCl3)δ8.07(t,J＝8.3Hz,2H),7.77(d,J＝8.1Hz,1H),7.70(td,J＝6.9Hz,1H),7.51(d,J＝8.4Hz,2H),7.43(d,J＝6.9Hz,2H),7.36(t,J＝7.6Hz,2H),7.30–7.22(m,1H),6.94–6.84(m,3H),6.80–6.69(m,1H),6.45(d,J＝8.4Hz,2H),4.55(dd,J＝8.2,5.0Hz,1H),2.94–2.84(m,1H),2.83–2.72(m,1H),2.18(s,3H).13C NMR(101MHz,CDCl3)δ155.76,148.01,144.97,143.59,136.57,134.25,133.33,129.89,129.71,129.18,128.84,127.61,127.42,127.25,126.74,126.44,126.34,118.74,113.72,57.78,42.65,20.46.HRMS(ESI):m/z 365.2019[M+H]+,calcd.for C26H25N2365.2018.
Example 13:
Experimental procedure reference example 1, petroleum ether/ethyl acetate mixed solvent as eluent (v: v=5:1), product yield 63%, yellow liquid.
1H NMR(500MHz,CDCl3)δ7.98–7.90(m,2H),7.42(d,J＝8.7Hz,1H),7.40–7.36(m,1H),7.34(d,J＝7.5Hz,2H),7.32–7.25(m,3H),7.18(d,J＝5.0Hz,1H),7.00(t,J＝7.7Hz,2H),6.76(d,J＝15.9Hz,1H),6.70–6.61(m,1H),6.57(t,J＝7.3Hz,1H),6.44(d,J＝8.0Hz,2H),4.49(t,J＝8.2,5.1Hz,1H),4.16(s,1H),2.85–2.76(m,1H),2.76–2.64(m,1H).13C NMR(126MHz,CDCl3)δ160.38(d,J＝247.5Hz),155.15,147.20,145.17,143.35,135.84(d,J＝5.4Hz),134.05,133.09,131.67(d,J＝9.1Hz),129.23,128.88,127.93(d,J＝10.0Hz),127.34,126.41,119.96(d,J＝25.5Hz),119.56,117.61,113.61,110.74(d,J＝21.4Hz),57.53,42.58.19F NMR(471MHz,CDCl3)δ-113.78.HRMS(ESI):m/z 367.1769[M+H]+,calcd.for C25H22FN2369.1766.
Example 14:
Experimental procedure reference example 1, petroleum ether/ethyl acetate mixed solvent as eluent (v: v=5:1), product yield 64%, yellow liquid.
1H NMR(400MHz,CDCl3)δ7.97(d,J＝8.7Hz,1H),7.94(d,J＝9.3Hz,1H),7.46(d,J＝8.6Hz,1H),7.44–7.40(m,2H),7.37(d,J＝3.0Hz,1H),7.36–7.32(m,2H),7.29–7.23(m,1H),7.10–7.03(m,3H),6.85(d,J＝15.7,1.3Hz,1H),6.70–6.60(m,2H),6.55–6.49(m,2H),4.56(dd,J＝8.1,5.0Hz,1H),3.93(s,3H),2.92–2.71(m,2H).13C NMR(101MHz,CDCl3)δ157.78,153.49,147.30,144.03,143.50,135.34,134.32,131.80,130.64,129.21,128.87,128.41,127.29,126.45,122.46,119.05,117.56,113.65,105.36,57.60,55.68,42.64.HRMS(ESI):m/z 403.1780[M+Na]+,calcd.for C26H24N2ONa 403.1786.
Example 15:
Experimental procedure reference example 1, petroleum ether/ethyl acetate mixed solvent as eluent (v: v=5:1), product yield 82%, yellow liquid.
1H NMR(400MHz,CDCl3)δ8.05(d,J＝8.5Hz,1H),7.94(d,J＝7.0Hz,1H),7.73–7.66(m,1H),7.56–7.48(m,1H),7.43(d,J＝9.6Hz,2H),7.37(d,3H),7.29–7.24(m,1H),7.08(dd,J＝8.6,7.3Hz,2H),6.85(d,J＝17.1Hz,1H),6.78–6.68(m,1H),6.65(t,1H),6.52(d,J＝6.3Hz,2H),4.57(dd,J＝8.2,5.0Hz,1H),2.94–2.72(m,2H),2.68(s,3H).13C NMR(101MHz,CDCl3)δ155.32,147.74,147.28,144.78,143.46,134.34,133.01,129.65,129.22,128.88,127.57,127.31,126.44,126.17,123.79,119.36,117.58,113.65,57.58,42.68,19.00.HRMS(ESI):m/z 387.1832[M+Na]+,calcd.for C26H24N2Na 387.1837.
Example 16:
experimental procedure reference example 1, petroleum ether/ethyl acetate mixed solvent as eluent (v: v=5:1), product yield 62%, yellow liquid.
1H NMR(400MHz,CDCl3)δ7.73(d,J＝8.3Hz,1H),7.47(d,J＝7.0Hz,1H),7.38(d,J＝7.4Hz,2H),7.36–7.28(m,3H),7.25–7.18(m,2H),7.02(d,2H),6.80(d,J＝16.0Hz,1H),6.76–6.67(m,1H),6.59(t,J＝7.3,0.9Hz,1H),6.47(d,2H),4.52(dd,J＝8.3,4.9Hz,1H),2.87–2.79(m,1H),2.76(s,3H),2.74–2.67(m,1H),2.61(d,J＝0.9Hz,3H).13C NMR(101MHz,CDCl3)δ153.97,147.35,147.02,144.50,143.61,137.75,134.93,131.97,129.67,129.21,128.85,127.46,127.27,126.45,125.64,121.65,119.36,117.55,113.68,57.65,42.66,19.26,18.42.HRMS(ESI):m/z 401.1990[M+Na]+,calcd.for C27H26N2Na401.1994.
Claims (4)
1. A synthesis method of quinoline-substituted homoallylamine compounds is characterized in that:
N-aryl imine shown in 1a is used as an electrophile, allylquinoline shown in 2a or allylquinoline with partial substituent is used as an allylation reagent, and quinoline substituted homoallylamine compounds are prepared by a cross coupling method in the presence of a catalyst, alkali and a solvent under the air atmosphere and the room temperature condition;
the reaction scheme is as follows:
;
R 1、R2、R3 is independently selected from one of hydrogen, methoxy, phenoxy, methyl, hydroxyl, fluorine, chlorine, bromine, nitro and trifluoromethyl;
The catalyst is boron trifluoride diethyl ether or ferric chloride;
The solvent is methanol;
The base is selected from sodium methoxide or triethylamine.
2. The synthesis method according to claim 1, wherein:
the catalyst is boron trifluoride diethyl etherate.
3. The synthesis method according to claim 1, wherein:
the base is triethylamine.
4. The synthesis method according to claim 1, wherein:
The feeding mole ratio of 1a, 2a, catalyst and alkali is 1.0:2.0-2.5:0.5:0.5.
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