CN114250479B - Novel method for synthesizing alkyl-substituted nitrogen-containing heterocycle by cerium salt catalysis - Google Patents

Novel method for synthesizing alkyl-substituted nitrogen-containing heterocycle by cerium salt catalysis Download PDF

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CN114250479B
CN114250479B CN202111515624.3A CN202111515624A CN114250479B CN 114250479 B CN114250479 B CN 114250479B CN 202111515624 A CN202111515624 A CN 202111515624A CN 114250479 B CN114250479 B CN 114250479B
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CN114250479A (en
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徐坤
谭周美
曾程初
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Beijing University of Technology
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Abstract

A novel method for synthesizing alkyl-substituted nitrogen-containing heterocycle by cerium salt catalysis belongs to the field of photoelectrocatalysis and synthesis. Adding nitrogen-containing heterocycle (II) and alkane (III) into a single-chamber electrolytic tank, then adding cerium salt catalyst, supporting electrolyte, alcohol, acid and solvent, then electrolyzing the mixed solution under constant current, and simultaneously using light source light irradiation to react in the electrolytic process to obtain the alkyl-substituted nitrogen-containing heterocycle compound shown in the formula I. The invention prepares the alkyl substituted nitrogen-containing heterocyclic compound efficiently and green without adding chemical oxidation-reduction reagent.

Description

Novel method for synthesizing alkyl-substituted nitrogen-containing heterocycle by cerium salt catalysis
Technical Field
The invention uses CeCl 3 ·7H 2 O is used as a catalyst, and alkyl substituted nitrogen heterocycle is synthesized in a green way through direct coupling reaction of the nitrogen heterocycle and alkane under the photoelectric synergistic effect, and belongs to the field of photoelectrocatalysis and synthesis.
Background
Alkyl-substituted nitrogen-containing heterocycles are an important class of building blocks that are widely found in natural products and drug molecules. Among the numerous synthetic routes to alkyl-substituted nitrogen-containing heterocycles, the direct coupling method of nitrogen-containing heterocycles and alkanes has the highest atomic and step economics. The main reason is that the method does not need to perform pre-activation of the substrate, and the byproduct of the reaction is water or hydrogen. At present, the coupling reaction of nitrogen-containing heterocycles and alkanes is mainly carried out by means of an excess of strong oxidizing agents and high temperature conditions (Angew. Chem. Int. Ed.2013,52,3267-3271; chem. Sci.2017,8, 4044-4050). Later developed photochemical processes can drive this type of coupling reaction at room temperature, but reported synthetic processes still require the use of excessive amounts of strong oxidants such as peroxides (chem. Sci.2019,10, 5018-5024), high valent iodine compounds (nat. Commun.2018,9, 3343-3350), potassium persulfate (org. Lett.2020,22, 7709-7715), and the like. Although the above synthetic method can efficiently prepare the alkyl-substituted nitrogen-containing heterocycle, the use of an excessive amount of strong oxidizer brings about an increase in production cost on the one hand and serious environmental problems on the other hand due to waste discharged after the reaction. In view of the important role of the alkyl substituted nitrogen-containing heterocycle and the importance of the nation on environmental protection, a green and efficient synthesis method is developed, and the method for realizing the coupling reaction of the nitrogen-containing heterocycle and alkane under the condition of no need of an external oxidant has important research significance and application value.
Disclosure of Invention
Aiming at the difficult problems encountered in the synthesis of the alkyl-substituted nitrogen-containing heterocycle, the invention aims to provide a green synthesis method with cerium salt catalysis and photoelectric synergistic effect, which is used for the direct coupling reaction of the nitrogen-containing heterocycle and alkane, and the alkyl-substituted nitrogen-containing heterocycle compound can be prepared in a high-efficiency and green manner under the condition of no external chemical redox reagent.
The invention provides a novel method for synthesizing an alkyl-substituted nitrogen-containing heterocyclic compound by photoelectrocatalysis, which comprises the following steps:
adding nitrogen-containing heterocycle (II) and alkane (III) into a single-chamber electrolytic tank, then adding cerium salt catalyst, supporting electrolyte, alcohol, acid and solvent, then electrolyzing the mixed solution under constant current, and simultaneously using light source light irradiation to react in the electrolytic process to obtain the alkyl-substituted nitrogen-containing heterocycle compound shown in the formula I.
In the compound 1, alkyl is alkyl corresponding to alkane (III).
The nitrogen heterocyclic compound is a nitrogen heterocyclic compound, wherein the nitrogen heterocyclic compound contains one N or two N and the like, and the nitrogen heterocyclic compound can also contain other hetero atoms such as O, S and the like, and can have different substituents such as alkyl, alkoxy, aromatic group, ester group, nitro, halogen, CN, amino and the like.
The cerium salt catalyst is selected from any one of cerium chloride, cerium chloride heptahydrate, cerium sulfate, cerium nitrate, cerium triflate and cerium oxalate, and is preferably cerium chloride; the amount of cerium salt catalyst is preferably such that the molar ratio of nitrogen-containing heterocycle to cerium salt catalyst is 1:0.2.
the supporting electrolyte is selected from any one of tetrabutylammonium chloride, tetraethylammonium chloride, tetramethyl ammonium chloride, hexafluoroammonium phosphate, tetrabutyl ammonium tetrafluoroborate and ammonium bisulfate; preferably tetrabutylammonium chloride; the amount of supporting electrolyte is preferably such that the molar ratio of nitrogen-containing heterocycle to supporting electrolyte is 1:1.
the alcohol is preferably methanol; the amount of methanol used is preferably 1.6% by volume of methanol.
The acid is one of trifluoromethanesulfonic acid, hydrochloric acid, sulfuric acid and trifluoroacetic acid; preferably trifluoromethanesulfonic acid; the molar ratio of the nitrogen-containing heterocycle to the trifluoromethanesulfonic acid is preferably 1:4.
the solvent is preferably any volume mixed solvent of acetonitrile and chlorobenzene; the ratio of acetonitrile to chlorobenzene is preferably 2:1.
The electrode for electrolysis is preferably a graphite felt electrode as an anode and foam nickel as a cathode.
The light source is a 390nm LED lamp, and the power is 30W.
The temperature is 30-70 ℃; preferably 50 ℃.
The concentration of the nitrogen-containing heterocycle in the electrolyte is 0.01-0.1mol/L, preferably 0.05mol/L.
The mol ratio of the alkane to the nitrogen-containing heterocycle is (20-35): 1, preferably 30:1.
Constant current has a current density of 2mA/cm 2 。
Advantages of the invention
(1) The method of the invention uses cheap cerium salt as a catalyst, uses cheap graphite felt and foamed nickel as an electrode, and has lower reaction cost.
(2) The method of the invention uses the synergistic effect of photoelectricity, uses clean electrons as oxidant to replace toxic and harmful chemical oxidizing agent, has low energy consumption and discharge of three wastes, and accords with the concept of green chemistry and the strategic requirement of double carbon.
(3) The method can synthesize alkylated nitrogen-containing heterocyclic compounds with various substituent groups, and has wide substrate application range.
(4) The method realizes the coupling reaction of the nitrogen-containing heterocycle and alkane catalyzed by the cerium salt in the first example, and has strong innovation.
Drawings
FIG. 1 is a reaction scheme of the present invention.
Detailed Description
The experimental methods used in the following examples are conventional methods unless otherwise specified.
Materials, reagents and the like used in the examples described below are commercially available unless otherwise specified. The present invention will be further illustrated with reference to the following examples, but the present invention is not limited to the following examples.
Example 1: photoelectrochemical synthesis of 1-cyclohexylisoquinoline
Raw materials isoquinoline (0.3 mmol), cyclohexane (1 mL) and CeCl were added to a single-chamber electrolytic cell 3 ·7H 2 O(0.06mmol，20mol％)、n-Bu 4 NCl(0.3mmol)、CF 3 COOH (1.2 mmol) and MeOH (0.2 mL). Acetonitrile: chlorobenzene = 2:1 (V/V, 6.0 mL) as solvent, and graphite felt as anode (1.0X1.0 cm) 2 ) The cathode is foam nickel (1.0X1.0 cm) 2 ). 390nm LEDs (30W) were placed at about 3.5cm in the reaction cell. Stirring and electrifying under water bath condition of 50deg.C to give illumination with current density of 2mA/cm 2 TLC detects the progress of the reaction. When TLC detects that the raw material isoquinoline disappears, the illumination and the power on are stopped, and the reaction is finished. The reaction system was added with aqueous NaOH until it became alkaline, extracted with ethyl acetate (30 mL. Times.3), dried, distilled under reduced pressure to remove the solvent, and finally separated by column chromatography to obtain the objective product. Yield: 79%.
Light yellow oil(50mg,79％). 1 H NMR(400MHz,CDCl 3 )δ8.50(d,J＝5.7Hz,1H),8.24(d,J＝8.4Hz,1H),7.82(dd,J＝8.1,1.4Hz,1H),7.66(m,1H),7.60(m,1H),7.50(dd,J＝5.7,0.9Hz,1H),3.59(tt,J＝11.7,3.3Hz,1H),2.09–1.78(m,7H),1.65–1.39(m,3H). 13 C NMR(100MHz,CDCl 3 )δ165.7,141.9,136.4,129.5,127.6,126.8,126.3,124.7,118.9,41.5,32.6,26.9,26.3.
Example 2: photoelectrochemical synthesis of methyl 1-cyclohexylisoquinoline-3-carboxylate
Raw materials of isoquinoline-3 methyl formate (0.3 mmol), cyclohexane (1 mL) and CeCl are respectively added into a single-chamber electrolytic cell 3 ·7H 2 O(0.06mmol，20mol％)、n-Bu 4 NCl(0.3mmol)、CF 3 COOH (1.2 mmol) and MeOH (0.2 mL). Acetonitrile: chlorobenzene = 2:1 (V/V, 6.0 mL) as solvent, and graphite felt as anode (1.0X1.0 cm) 2 ) The cathode is foam nickel (1.0X1.0 cm) 2 ). 390nm LEDs (30W) were placed at about 3.5cm in the reaction cell. Stirring and electrifying under water bath condition of 50deg.C to give illumination with current density of 2mA/cm 2 TLC detects the progress of the reaction. When TLC detects that the raw material isoquinoline disappears, the illumination and the power on are stopped, and the reaction is finished. The reaction system was added with aqueous NaOH until it became alkaline, extracted with ethyl acetate (30 mL. Times.3), dried, distilled under reduced pressure to remove the solvent, and finally separated by column chromatography to obtain the objective product. Yield: 44%.
Example 3: photoelectrochemical synthesis of 1-cyclohexyl-4-cyanoisoquinoline
The raw materials 4-cyanoisoquinoline (0.3 mmol), cyclohexane (1 mL) and CeCl were added to a single-chamber cell 3 ·7H 2 O(0.06mmol，20mol％)、n-Bu 4 NCl(0.3mmol)、CF 3 COOH (1.2 mmol) and MeOH (0.2 mL). Acetonitrile: chlorobenzene = 2:1 (V/V, 6.0 mL) as solvent, and graphite felt as anode (1.0X1.0 cm) 2 ) The cathode is foam nickel (1.0X1.0 cm) 2 ). 390nm LEDs (30W) were placed at about 3.5cm in the reaction cell. Stirring and electrifying under water bath condition of 50deg.C to give illumination with current density of 2mA/cm 2 TLC detects the progress of the reaction. When TLC detects that the raw material isoquinoline disappears, the illumination and the power on are stopped, and the reaction is finished. The reaction bodyAqueous NaOH solution was added to the mixture to be alkaline, extraction was performed with ethyl acetate (30 mL. Times.3), the mixture was dried, the solvent was distilled off under reduced pressure, and finally the desired product was obtained by column chromatography. Yield: 45%.
Example 4: photoelectrochemical synthesis of 2-cyclohexyl-4-methylquinoline
The raw materials 4-methylquinoline (0.3 mmol), cyclohexane (1 mL) and CeCl were added to a single-chamber electrolytic cell 3 ·7H 2 O(0.06mmol，20mol％)、n-Bu 4 NCl(0.3mmol)、CF 3 COOH (1.2 mmol) and MeOH (0.2 mL). Acetonitrile: chlorobenzene = 2:1 (V/V, 6.0 mL) as solvent, and graphite felt as anode (1.0X1.0 cm) 2 ) The cathode is foam nickel (1.0X1.0 cm) 2 ). 390nm LEDs (30W) were placed at about 3.5cm in the reaction cell. Stirring and electrifying under water bath condition of 50deg.C to give illumination with current density of 2mA/cm 2 TLC detects the progress of the reaction. When TLC detects that the raw material isoquinoline disappears, the illumination and the power on are stopped, and the reaction is finished. The reaction system was added with aqueous NaOH until it became alkaline, extracted with ethyl acetate (30 mL. Times.3), dried, distilled under reduced pressure to remove the solvent, and finally separated by column chromatography to obtain the objective product. Yield: 65%.
Example 5: photoelectrochemical synthesis of 2-cyclohexyl-4-methoxyquinoline
The raw materials 4-methoxyquinoline (0.3 mmol), cyclohexane (1 mL) and CeCl are respectively added into a single-chamber electrolytic cell 3 ·7H 2 O(0.06mmol，20mol％)、n-Bu 4 NCl(0.3mmol)、CF 3 COOH (1.2 mmol) and MeOH (0.2 mL). Acetonitrile: chlorobenzene = 2:1 (V/V, 6.0 mL) as solvent, and graphite felt as anode (1.0X1.0 cm) 2 ) The cathode is foam nickel (1.0X1.0 cm) 2 ). 390nm LEDs (30W) were placed at about 3.5cm in the reaction cell. Stirring and electrifying under the water bath condition of 50 ℃ to give illumination,the current density was 2mA/cm 2 TLC detects the progress of the reaction. When TLC detects that the raw material isoquinoline disappears, the illumination and the power on are stopped, and the reaction is finished. The reaction system was added with aqueous NaOH until it became alkaline, extracted with ethyl acetate (30 mL. Times.3), dried, distilled under reduced pressure to remove the solvent, and finally separated by column chromatography to obtain the objective product. Yield: 47%.
Example 6: photoelectrochemical synthesis of 2-cyclohexyl-4-chloroquinoline
The raw materials 4-chloroquinoline (0.3 mmol), cyclohexane (1 mL) and CeCl are respectively added into a single-chamber electrolytic cell 3 ·7H 2 O(0.06mmol，20mol％)、n-Bu 4 NCl(0.3mmol)、CF 3 COOH (1.2 mmol) and MeOH (0.2 mL). Acetonitrile: chlorobenzene = 2:1 (V/V, 6.0 mL) as solvent, and graphite felt as anode (1.0X1.0 cm) 2 ) The cathode is foam nickel (1.0X1.0 cm) 2 ). 390nm LEDs (30W) were placed at about 3.5cm in the reaction cell. Stirring and electrifying under water bath condition of 50deg.C to give illumination with current density of 2mA/cm 2 TLC detects the progress of the reaction. When TLC detects that the raw material isoquinoline disappears, the illumination and the power on are stopped, and the reaction is finished. The reaction system was added with aqueous NaOH until it became alkaline, extracted with ethyl acetate (30 mL. Times.3), dried, distilled under reduced pressure to remove the solvent, and finally separated by column chromatography to obtain the objective product. Yield: 47%.
Example 7: photoelectrochemical synthesis of 2-cyclohexyl-4-chloro-6-methoxyquinoline
The raw materials 4-chloro-6-methoxyquinoline (0.3 mmol), cyclohexane (1 mL) and CeCl are respectively added into a single-chamber electrolytic cell 3 ·7H 2 O(0.06mmol，20mol％)、n-Bu 4 NCl(0.3mmol)、CF 3 COOH (1.2 mmol) and MeOH (0.2 mL). Acetonitrile: chlorobenzene = 2:1 (V/V, 6.0 mL) as solvent, and graphite felt as anode (1.0X1.0 cm) 2 ) The cathode is foam nickel (1.0X1.0 cm) 2 ). 390nm LEDs (30W) were placed at about 3.5cm in the reaction cell. Stirring and electrifying under water bath condition of 50deg.C to give illumination with current density of 2mA/cm 2 TLC detects the progress of the reaction. When TLC detects that the raw material isoquinoline disappears, the illumination and the power on are stopped, and the reaction is finished. The reaction system was added with aqueous NaOH until it became alkaline, extracted with ethyl acetate (30 mL. Times.3), dried, distilled under reduced pressure to remove the solvent, and finally separated by column chromatography to obtain the objective product. Yield: 40 percent of
Example 8: photoelectrochemical synthesis of 2-cyclohexyl-4-chloro-6, 7-dimethoxy quinoline
The raw materials of 4-chloro-6, 7-dimethoxy quinoline (0.3 mmol), cyclohexane (1 mL) and CeCl are respectively added into a single-chamber electrolytic cell 3 ·7H 2 O(0.06mmol，20mol％)、n-Bu 4 NCl(0.3mmol)、CF 3 COOH (1.2 mmol) and MeOH (0.2 mL). Acetonitrile: chlorobenzene = 2:1 (V/V, 6.0 mL) as solvent, and graphite felt as anode (1.0X1.0 cm) 2 ) The cathode is foam nickel (1.0X1.0 cm) 2 ). 390nm LEDs (30W) were placed at about 3.5cm in the reaction cell. Stirring and electrifying under water bath condition of 50deg.C to give illumination with current density of 2mA/cm 2 TLC detects the progress of the reaction. When TLC detects that the raw material isoquinoline disappears, the illumination and the power on are stopped, and the reaction is finished. The reaction system was added with aqueous NaOH until it became alkaline, extracted with ethyl acetate (30 mL. Times.3), dried, distilled under reduced pressure to remove the solvent, and finally separated by column chromatography to obtain the objective product. Yield: 64%.
Example 9: photoelectrochemical synthesis of 2-cyclohexyl-4-phenylquinoline
The raw materials 4-phenylquinoline (0.3 mmol), cyclohexane (1 mL) and CeCl were added to a single-chamber cell 3 ·7H 2 O(0.06mmol，20mol％)、n-Bu 4 NCl(0.3mmol)、CF 3 COOH (1.2 mmol) and MeOH (0.2 mL). Acetonitrile: chlorobenzene = 2:1 (V/V, 6.0 mL) as solvent, and graphite felt as anode (1.0X1.0 cm) 2 ) The cathode is foam nickel (1.0X1.0 cm) 2 ). 390nm LEDs (30W) were placed at about 3.5cm in the reaction cell. Stirring and electrifying under water bath condition of 50deg.C to give illumination with current density of 2mA/cm 2 TLC detects the progress of the reaction. When TLC detects that the raw material isoquinoline disappears, the illumination and the power on are stopped, and the reaction is finished. The reaction system was added with aqueous NaOH until it became alkaline, extracted with ethyl acetate (30 mL. Times.3), dried, distilled under reduced pressure to remove the solvent, and finally separated by column chromatography to obtain the objective product. Yield: 73%.
Example 10: photoelectrochemical synthesis of 2-cyclohexyl-4- (4-methylphenyl) quinoline
The raw materials 4- (4-methylphenyl) quinoline (0.3 mmol), cyclohexane (1 mL) and CeCl were added to a single-chamber electrolytic cell 3 ·7H 2 O(0.06mmol，20mol％)、n-Bu 4 NCl(0.3mmol)、CF 3 COOH (1.2 mmol) and MeOH (0.2 mL). Acetonitrile: chlorobenzene = 2:1 (V/V, 6.0 mL) as solvent, and graphite felt as anode (1.0X1.0 cm) 2 ) The cathode is foam nickel (1.0X1.0 cm) 2 ). 390nm LEDs (30W) were placed at about 3.5cm in the reaction cell. Stirring and electrifying under water bath condition of 50deg.C to give illumination with current density of 2mA/cm 2 TLC detects the progress of the reaction. When TLC detects that the raw material isoquinoline disappears, the illumination and the power on are stopped, and the reaction is finished. The reaction system was added with aqueous NaOH until it became alkaline, extracted with ethyl acetate (30 mL. Times.3), dried, distilled under reduced pressure to remove the solvent, and finally separated by column chromatography to obtain the objective product. Yield: 63%.
Example 11: photoelectrochemical synthesis of 2-cyclohexyl-4- (4-tert-butylphenyl) quinoline
The raw materials 4- (4-tert-butylphenyl) quinoline (0.3 mmol), cyclohexane (1 mL) and CeCl were added to a single-chamber cell 3 ·7H 2 O(0.06mmol，20mol％)、n-Bu 4 NCl(0.3mmol)、CF 3 COOH (1.2 mmol) and MeOH (0.2 mL). Acetonitrile: chlorobenzene = 2:1 (V/V, 6.0 mL) as solvent, and graphite felt as anode (1.0X1.0 cm) 2 ) The cathode is foam nickel (1.0X1.0 cm) 2 ). 390nm LEDs (30W) were placed at about 3.5cm in the reaction cell. Stirring and electrifying under water bath condition of 50deg.C to give illumination with current density of 2mA/cm 2 TLC detects the progress of the reaction. When TLC detects that the raw material isoquinoline disappears, the illumination and the power on are stopped, and the reaction is finished. The reaction system was added with aqueous NaOH until it became alkaline, extracted with ethyl acetate (30 mL. Times.3), dried, distilled under reduced pressure to remove the solvent, and finally separated by column chromatography to obtain the objective product. Yield: 71%.
Example 12: photoelectrochemical synthesis of 2-cyclohexyl-4- (3-biphenyl) quinoline
The raw materials 4- (3-biphenylyl) quinoline (0.3 mmol), cyclohexane (1 mL) and CeCl were added to a single-chamber cell 3 ·7H 2 O(0.06mmol，20mol％)、n-Bu 4 NCl(0.3mmol)、CF 3 COOH (1.2 mmol) and MeOH (0.2 mL). Acetonitrile: chlorobenzene = 2:1 (V/V, 6.0 mL) as solvent, and graphite felt as anode (1.0X1.0 cm) 2 ) The cathode is foam nickel (1.0X1.0 cm) 2 ). 390nm LEDs (30W) were placed at about 3.5cm in the reaction cell. Stirring and electrifying under water bath condition of 50deg.C to give illumination with current density of 2mA/cm 2 TLC detects the progress of the reaction. When TLC detects that the raw material isoquinoline disappears, the illumination and the power on are stopped, and the reaction is finished. The reaction system was added with aqueous NaOH until it became alkaline, extracted with ethyl acetate (30 mL. Times.3), dried, distilled under reduced pressure to remove the solvent, and finally separated by column chromatography to obtain the objective product. Yield: 77%.
Example 13: photoelectrochemical synthesis of 3-cyclohexyl-N-methylquinoxalinone
Raw materials N-methylquinoxalinone (0.3 mmol), cyclohexane (1 mL) and CeCl were added to a single-chamber electrolytic cell 3 ·7H 2 O(0.06mmol，20mol％)、n-Bu 4 NCl(0.3mmol)、CF 3 COOH (1.2 mmol) and MeOH (0.2 mL). Acetonitrile: chlorobenzene = 2:1 (V/V, 6.0 mL) as solvent, and graphite felt as anode (1.0X1.0 cm) 2 ) The cathode is foam nickel (1.0X1.0 cm) 2 ). 390nm LEDs (30W) were placed at about 3.5cm in the reaction cell. Stirring and electrifying under water bath condition of 50deg.C to give illumination with current density of 2mA/cm 2 TLC detects the progress of the reaction. When TLC detects that the raw material isoquinoline disappears, the illumination and the power on are stopped, and the reaction is finished. The reaction system was added with aqueous NaOH until it became alkaline, extracted with ethyl acetate (30 mL. Times.3), dried, distilled under reduced pressure to remove the solvent, and finally separated by column chromatography to obtain the objective product. Yield: 66%.
Example 14: photoelectrochemical synthesis of 3-cyclohexyl-N-benzyl quinoxalinone
Raw materials N-benzylquinoxalinone (0.3 mmol), cyclohexane (1 mL) and CeCl were added to a single-chamber electrolytic cell 3 ·7H 2 O(0.06mmol，20mol％)、n-Bu 4 NCl(0.3mmol)、CF 3 COOH (1.2 mmol) and MeOH (0.2 mL). Acetonitrile: chlorobenzene = 2:1 (V/V, 6.0 mL) as solvent, and graphite felt as anode (1.0X1.0 cm) 2 ) The cathode is foam nickel (1.0X1.0 cm) 2 ). 390nm LEDs (30W) were placed at about 3.5cm in the reaction cell. Stirring and electrifying under water bath condition of 50deg.C to give illumination with current density of 2mA/cm 2 TLC detects the progress of the reaction. When TLC detects that the raw material isoquinoline disappears, the illumination and the power on are stopped, and the reaction is finished. The reaction system was added with an aqueous NaOH solution to be alkaline, extracted with ethyl acetate (30 mL. Times.3), dried, and distilled under reduced pressure to removeRemoving solvent, and separating by column chromatography to obtain the target product. Yield: 51%.
Example 15: photoelectrochemical synthesis of ethyl 2- (3-cyclohexyl-2-quinoxalinone) acetate
Raw materials of ethyl 2- (2-quinoxalinone) acetate (0.3 mmol), cyclohexane (1 mL) and CeCl were added to a single-chamber electrolytic cell, respectively 3 ·7H 2 O(0.06mmol，20mol％)、n-Bu 4 NCl(0.3mmol)、CF 3 COOH (1.2 mmol) and MeOH (0.2 mL). Acetonitrile: chlorobenzene = 2:1 (V/V, 6.0 mL) as solvent, and graphite felt as anode (1.0X1.0 cm) 2 ) The cathode is foam nickel (1.0X1.0 cm) 2 ). 390nm LEDs (30W) were placed at about 3.5cm in the reaction cell. Stirring and electrifying under water bath condition of 50deg.C to give illumination with current density of 2mA/cm 2 TLC detects the progress of the reaction. When TLC detects that the raw material isoquinoline disappears, the illumination and the power on are stopped, and the reaction is finished. The reaction system was added with aqueous NaOH until it became alkaline, extracted with ethyl acetate (30 mL. Times.3), dried, distilled under reduced pressure to remove the solvent, and finally separated by column chromatography to obtain the objective product. Yield: 72%.
Example 16: photoelectrochemical synthesis of 2-cyclohexyl-4-phenylpyridine
The raw materials 4-phenylpyridine (0.3 mmol), cyclohexane (1 mL) and CeCl were added to a single-chamber electrolytic cell 3 ·7H 2 O(0.06mmol，20mol％)、n-Bu 4 NCl(0.3mmol)、CF 3 COOH (1.2 mmol) and MeOH (0.2 mL). Acetonitrile: chlorobenzene = 2:1 (V/V, 6.0 mL) as solvent, and graphite felt as anode (1.0X1.0 cm) 2 ) The cathode is foam nickel (1.0X1.0 cm) 2 ). 390nm LEDs (30W) were placed at about 3.5cm in the reaction cell. Stirring and electrifying under water bath condition of 50deg.C to give illumination with current density of 2mA/cm 2 TLC detects the progress of the reaction.When TLC detects that the raw material isoquinoline disappears, the illumination and the power on are stopped, and the reaction is finished. The reaction system was added with aqueous NaOH until it became alkaline, extracted with ethyl acetate (30 mL. Times.3), dried, distilled under reduced pressure to remove the solvent, and finally separated by column chromatography to obtain the objective product. Yield: 58%.
Example 17: photoelectrochemical synthesis of 6-cyclohexylphenanthridine
The raw materials phenanthridine (0.3 mmol), cyclohexane (1 mL) and CeCl are respectively added into a single-chamber electrolytic cell 3 ·7H 2 O(0.06mmol，20mol％)、n-Bu 4 NCl(0.3mmol)、CF 3 COOH (1.2 mmol) and MeOH (0.2 mL). Acetonitrile: chlorobenzene = 2:1 (V/V, 6.0 mL) as solvent, and graphite felt as anode (1.0X1.0 cm) 2 ) The cathode is foam nickel (1.0X1.0 cm) 2 ). 390nm LEDs (30W) were placed at about 3.5cm in the reaction cell. Stirring and electrifying under water bath condition of 50deg.C to give illumination with current density of 2mA/cm 2 TLC detects the progress of the reaction. When TLC detects that the raw material isoquinoline disappears, the illumination and the power on are stopped, and the reaction is finished. The reaction system was added with aqueous NaOH until it became alkaline, extracted with ethyl acetate (30 mL. Times.3), dried, distilled under reduced pressure to remove the solvent, and finally separated by column chromatography to obtain the objective product. Yield: 89%.
Example 18: photoelectrochemical synthesis of 2-cyclohexylbenzothiazole
The raw materials benzothiazole (0.3 mmol), cyclohexane (1 mL) and CeCl are respectively added into a single-chamber electrolytic cell 3 ·7H 2 O(0.06mmol，20mol％)、n-Bu 4 NCl(0.3mmol)、CF 3 COOH (1.2 mmol) and MeOH (0.2 mL). Acetonitrile: chlorobenzene = 2:1 (V/V, 6.0 mL) as solvent, and graphite felt as anode (1.0X1.0 cm) 2 ) The cathode is foam nickel (1.0X1.0 cm) 2 ). 390nm LEDs (30W) were placed in a reaction cell3.5 cm. Stirring and electrifying under water bath condition of 50deg.C to give illumination with current density of 2mA/cm 2 TLC detects the progress of the reaction. When TLC detects that the raw material isoquinoline disappears, the illumination and the power on are stopped, and the reaction is finished. The reaction system was added with aqueous NaOH until it became alkaline, extracted with ethyl acetate (30 mL. Times.3), dried, distilled under reduced pressure to remove the solvent, and finally separated by column chromatography to obtain the objective product. Yield: 40%.
Example 19: photoelectrochemical synthesis of 1-cyclopentylisoquinoline
Raw materials isoquinoline (0.3 mmol), cyclopentane (1 mL) and CeCl are respectively added into a single-chamber electrolytic cell 3 ·7H 2 O(0.06mmol，20mol％)、n-Bu 4 NCl(0.3mmol)、CF 3 COOH (1.2 mmol) and MeOH (0.2 mL). Acetonitrile: chlorobenzene = 2:1 (V/V, 6.0 mL) as solvent, and graphite felt as anode (1.0X1.0 cm) 2 ) The cathode is foam nickel (1.0X1.0 cm) 2 ). 390nm LEDs (30W) were placed at about 3.5cm in the reaction cell. Stirring and electrifying under water bath condition of 50deg.C to give illumination with current density of 2mA/cm 2 TLC detects the progress of the reaction. When TLC detects that the raw material isoquinoline disappears, the illumination and the power on are stopped, and the reaction is finished. The reaction system was added with aqueous NaOH until it became alkaline, extracted with ethyl acetate (30 mL. Times.3), dried, distilled under reduced pressure to remove the solvent, and finally separated by column chromatography to obtain the objective product. Yield: 65%.
Example 20: photoelectrochemical synthesis of 1-cycloheptylisoquinoline
Raw materials isoquinoline (0.3 mmol), cycloheptane (1 mL) and CeCl are respectively added into a single-chamber electrolytic cell 3 ·7H 2 O(0.06mmol，20mol％)、n-Bu 4 NCl(0.3mmol)、CF 3 COOH (1.2 mmol) and MeOH (0.2 mL). Acetonitrile: chlorobenzene = 2:1 (V/V, 6.0 mL) as solvent and the anode as stoneInk felt (1.0X1.0 cm) 2 ) The cathode is foam nickel (1.0X1.0 cm) 2 ). 390nm LEDs (30W) were placed at about 3.5cm in the reaction cell. Stirring and electrifying under water bath condition of 50deg.C to give illumination with current density of 2mA/cm 2 TLC detects the progress of the reaction. When TLC detects that the raw material isoquinoline disappears, the illumination and the power on are stopped, and the reaction is finished. The reaction system was added with aqueous NaOH until it became alkaline, extracted with ethyl acetate (30 mL. Times.3), dried, distilled under reduced pressure to remove the solvent, and finally separated by column chromatography to obtain the objective product. Yield: 89%.
Example 21: photoelectrochemical synthesis of 1-cyclooctylisoquinoline
Raw materials of isoquinoline (0.3 mmol), cyclooctane (1 mL) and CeCl are respectively added into a single-chamber electrolytic cell 3 ·7H 2 O(0.06mmol，20mol％)、n-Bu 4 NCl(0.3mmol)、CF 3 COOH (1.2 mmol) and MeOH (0.2 mL). Acetonitrile: chlorobenzene = 2:1 (V/V, 6.0 mL) as solvent, and graphite felt as anode (1.0X1.0 cm) 2 ) The cathode is foam nickel (1.0X1.0 cm) 2 ). 390nm LEDs (30W) were placed at about 3.5cm in the reaction cell. Stirring and electrifying under water bath condition of 50deg.C to give illumination with current density of 2mA/cm 2 TLC detects the progress of the reaction. When TLC detects that the raw material isoquinoline disappears, the illumination and the power on are stopped, and the reaction is finished. The reaction system was added with aqueous NaOH until it became alkaline, extracted with ethyl acetate (30 mL. Times.3), dried, distilled under reduced pressure to remove the solvent, and finally separated by column chromatography to obtain the objective product. Yield: 56%.
Example 22: photoelectrochemical synthesis of 1-cyclododecyl isoquinoline
Raw materials isoquinoline (0.3 mmol), cyclododecane (1 mL) and CeCl are respectively added into a single-chamber electrolytic cell 3 ·7H 2 O(0.06mmol，20mol％)、n-Bu 4 NCl(0.3mmol)、CF 3 COOH (1.2 mmol) and MeOH (0.2 mL). Acetonitrile: chlorobenzene = 2:1 (V/V, 6.0 mL) as solvent, and graphite felt as anode (1.0X1.0 cm) 2 ) The cathode is foam nickel (1.0X1.0 cm) 2 ). 390nm LEDs (30W) were placed at about 3.5cm in the reaction cell. Stirring and electrifying under water bath condition of 50deg.C to give illumination with current density of 2mA/cm 2 TLC detects the progress of the reaction. When TLC detects that the raw material isoquinoline disappears, the illumination and the power on are stopped, and the reaction is finished. The reaction system was added with aqueous NaOH until it became alkaline, extracted with ethyl acetate (30 mL. Times.3), dried, distilled under reduced pressure to remove the solvent, and finally separated by column chromatography to obtain the objective product. Yield: 63%.
Example 23: photoelectrochemical synthesis of 1- (2-norbornyl) isoquinoline
Respectively adding raw materials of isoquinoline (0.3 mmol), norbornane (15 equiv) and CeCl into a single-chamber electrolytic cell 3 ·7H 2 O(0.06mmol，20mol％)、n-Bu 4 NCl(0.3mmol)、CF 3 COOH (1.2 mmol) and MeOH (0.2 mL). Acetonitrile: chlorobenzene = 2:1 (V/V, 6.0 mL) as solvent, and graphite felt as anode (1.0X1.0 cm) 2 ) The cathode is foam nickel (1.0X1.0 cm) 2 ). 390nm LEDs (30W) were placed at about 3.5cm in the reaction cell. Stirring and electrifying under water bath condition of 50deg.C to give illumination with current density of 2mA/cm 2 TLC detects the progress of the reaction. When TLC detects that the raw material isoquinoline disappears, the illumination and the power on are stopped, and the reaction is finished. The reaction system was added with aqueous NaOH until it became alkaline, extracted with ethyl acetate (30 mL. Times.3), dried, distilled under reduced pressure to remove the solvent, and finally separated by column chromatography to obtain the objective product. Yield: 61%.
Example 24: photoelectrochemical synthesis of 1- (2-n-pentanyl) isoquinoline and 1- (3-n-pentanyl) isoquinoline
Raw materials isoquinoline (0.3 mmol), n-pentane (1 mL) and CeCl are respectively added into a single-chamber electrolytic cell 3 ·7H 2 O(0.06mmol，20mol％)、n-Bu 4 NCl(0.3mmol)、CF 3 COOH (1.2 mmol) and MeOH (0.2 mL). Acetonitrile: chlorobenzene = 2:1 (V/V, 6.0 mL) as solvent, and graphite felt as anode (1.0X1.0 cm) 2 ) The cathode is foam nickel (1.0X1.0 cm) 2 ). 390nm LEDs (30W) were placed at about 3.5cm in the reaction cell. Stirring and electrifying under water bath condition of 50deg.C to give illumination with current density of 2mA/cm 2 TLC detects the progress of the reaction. When TLC detects that the raw material isoquinoline disappears, the illumination and the power on are stopped, and the reaction is finished. The reaction system was added with aqueous NaOH until it became alkaline, extracted with ethyl acetate (30 mL. Times.3), dried, distilled under reduced pressure to remove the solvent, and finally separated by column chromatography to obtain the objective product. Yield: 62%.
Example 25: photoelectrochemical synthesis of 1- (2-n-hexane-yl) isoquinoline and 1- (3-n-hexane-yl) isoquinoline
Raw materials isoquinoline (0.3 mmol), n-hexane (1 mL) and CeCl were added to a single-chamber electrolytic cell 3 ·7H 2 O(0.06mmol，20mol％)、n-Bu 4 NCl(0.3mmol)、CF 3 COOH (1.2 mmol) and MeOH (0.2 mL). Acetonitrile: chlorobenzene = 2:1 (V/V, 6.0 mL) as solvent, and graphite felt as anode (1.0X1.0 cm) 2 ) The cathode is foam nickel (1.0X1.0 cm) 2 ). 390nm LEDs (30W) were placed at about 3.5cm in the reaction cell. Stirring and electrifying under water bath condition of 50deg.C to give illumination with current density of 2mA/cm 2 TLC detects the progress of the reaction. When TLC detects that the raw material isoquinoline disappears, the illumination and the power on are stopped, and the reaction is finished. The reaction system was added with aqueous NaOH until it became alkaline, extracted with ethyl acetate (30 mL. Times.3), dried, distilled under reduced pressure to remove the solvent, and finally separated by column chromatography to obtain the objective product. Yield: 58%.
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Claims (11)

1. A method for synthesizing alkyl-substituted nitrogen-containing heterocycle by cerium salt catalysis, which is characterized by comprising the following steps of: adding a nitrogen-containing heterocycle (II) and alkane (III) into a single-chamber electrolytic tank, then adding a cerium salt catalyst, a supporting electrolyte, alcohol, acid and a solvent, and then electrolyzing the obtained mixed solution under a constant current condition, wherein light source light is used for irradiation reaction in the electrolysis process to obtain an alkyl-substituted nitrogen-containing heterocycle compound shown in a formula I;
in the compound I, the alkyl is alkyl corresponding to alkane (III);
the cerium salt catalyst is selected from any one of cerium chloride and cerium chloride heptahydrate; the dosage of the cerium salt catalyst is that the molar ratio of the nitrogen-containing heterocycle to the cerium salt catalyst is 1:0.2;
is a compound containing nitrogen heterocycle, wherein the nitrogen heterocycle contains one N or two N, or the nitrogen heterocycle also contains one or more of other hetero atoms O, S, or the nitrogen heterocycle also contains one or more of different substituents, namely alkyl, alkoxy, aromatic group, ester group, nitro, halogen, CN and amino; the acid is trifluoroacetic acid; the alcohol is methanol; the supporting electrolyte is selected from any one of tetrabutylammonium chloride, tetraethylammonium chloride and tetramethyl ammonium chloride; the electrode for electrolysis is a graphite felt electrode serving as an anode and foam nickel serving as a cathode.
2. The method of claim 1, wherein the supporting electrolyte is used in an amount such that the molar ratio of nitrogen-containing heterocycle to supporting electrolyte is 1:1, a step of; the mol ratio of the alkane to the nitrogen-containing heterocycle is (20-35): 1.
3. the method of claim 2, wherein the molar ratio of alkane to nitrogen-containing heterocycle is 30:1.
4. The method according to claim 1, wherein the amount of methanol used is 1.6% by volume of methanol in the mixed liquor.
5. The method according to claim 1, wherein the solvent is any volume mixed solvent of acetonitrile and chlorobenzene; the product ratio of acetonitrile to chlorobenzene was 2:1.
6. The method of claim 1, wherein the light source is a 390nm LED lamp with a power of 30W.
7. The process of claim 1, wherein the reaction temperature is from 30 to 70 ℃.
8. The method of claim 1, wherein the reaction temperature is 50 ℃.
9. The method of claim 1, wherein the concentration of the nitrogen-containing heterocycle in the electrolyte is 0.01 to 0.1mol/L, and the molar ratio of the alkane to the nitrogen-containing heterocycle is (20 to 35): 1.
10. the method of claim 1, wherein the concentration of the nitrogen-containing heterocycle in the electrolyte is 0.05mol/L, and the molar ratio of the alkane to the nitrogen-containing heterocycle is 30:1.
11. The method according to claim 1, wherein the constant current has a current density of 2mA/cm 2 。
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