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

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

A new method for synthesizing alkyl-substituted nitrogen-containing heterocycles catalyzed by cerium salts

Technical Field

The invention uses CeCl ₃ ·7H ₂ O as a catalyst, and under the synergistic effect of photoelectricity, greenly synthesizes alkyl-substituted nitrogen-containing heterocycles through direct coupling reaction of nitrogen-containing heterocycles and alkanes, belonging to the field of photoelectric catalysis and synthesis.

Background Art

Alkyl-substituted nitrogen-containing heterocycles are an important type of structural unit and are widely present in natural products and drug molecules. Among the numerous synthetic routes of alkyl-substituted nitrogen-containing heterocycles, the direct coupling method of nitrogen-containing heterocycles and alkanes has the highest atom economy and step economy. The main reason is that this method does not require pre-activation of the substrate, and the by-products of the reaction are water or hydrogen. At present, the coupling reaction of nitrogen-containing heterocycles and alkanes is mainly achieved by excess strong oxidants and high temperature conditions (Angew. Chem. Int. Ed. 2013, 52, 3267-3271; Chem. Sci. 2017, 8, 4044-4050). The photochemical method developed later can promote this type of coupling reaction at room temperature, but the reported synthesis method still requires the use of excessive 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), etc. Although the above-mentioned synthesis methods can efficiently prepare alkyl-substituted nitrogen-containing heterocycles, the use of excessive strong oxidants will increase production costs on the one hand, and the waste discharged after the reaction will cause serious environmental problems on the other hand. In view of the important role of alkyl-substituted nitrogen-containing heterocycles and the country's attention to environmental protection issues, it is of great research significance and application value to develop a green and efficient synthesis methodology to achieve the coupling reaction of nitrogen-containing heterocycles and alkanes without the addition of external oxidants.

Summary of the invention

In view of the difficulties encountered in the synthesis of alkyl-substituted nitrogen-containing heterocycles, the purpose of the present invention is to provide a green synthesis methodology with cerium salt catalysis and photoelectric synergy, and to use it for the direct coupling reaction of nitrogen-containing heterocycles and alkanes, so as to prepare alkyl-substituted nitrogen-containing heterocyclic compounds efficiently and greenly without the need for external chemical redox reagents.

The present invention provides a novel method for synthesizing alkyl-substituted nitrogen-containing heterocyclic compounds by photoelectric synergistic catalysis, comprising the following steps:

In a single-chamber electrolytic cell, nitrogen-containing heterocycle (II) and alkane (III) are added, and then a cerium salt catalyst, a supporting electrolyte, an alcohol, an acid and a solvent are added. The mixed solution is then electrolyzed under constant current conditions. During the electrolysis process, a light source is used to irradiate the reaction to obtain an alkyl-substituted nitrogen-containing heterocyclic compound as shown in Formula I.

In compound 1, alkyl is the alkyl group corresponding to alkane (III).

It is a nitrogen-containing heterocyclic compound, wherein the nitrogen heterocyclic ring contains one N or two N, etc., and the nitrogen heterocyclic ring may also contain other heteroatoms such as O, S, etc. The nitrogen heterocyclic ring may have different substituents, such as alkyl, alkoxy, aromatic, ester, nitro, halogen, CN, amine, etc.

The cerium salt catalyst is selected from any one of cerium chloride, cerium chloride heptahydrate, cerium sulfate, cerium nitrate, cerium trifluoromethanesulfonate and cerium oxalate, preferably cerium chloride; the amount of the cerium salt catalyst is preferably a molar ratio of nitrogen-containing heterocycle to cerium salt catalyst of 1:0.2.

The supporting electrolyte is selected from any one of tetrabutylammonium chloride, tetraethylammonium chloride, tetramethylammonium chloride, ammonium hexafluorophosphate, tetrabutylammonium tetrafluoroborate and ammonium hydrogen sulfate; preferably tetrabutylammonium chloride; the amount of the supporting electrolyte is preferably such that the molar ratio of the nitrogen-containing heterocycle to the supporting electrolyte is 1:1.

The alcohol is preferably methanol; the amount of methanol used is preferably such that the volume fraction of methanol is 1.6%.

The acid is one of trifluoromethanesulfonic acid, hydrochloric acid, sulfuric acid and trifluoroacetic acid; preferably trifluoromethanesulfonic acid; the molar ratio of nitrogen-containing heterocycle to trifluoromethanesulfonic acid is preferably 1:4.

The solvent is preferably a mixed solvent of acetonitrile and chlorobenzene in any volume; the volume ratio of acetonitrile to chlorobenzene is preferably 2:1.

The electrolysis electrode is preferably a graphite felt electrode as the anode and a nickel foam as the cathode.

The light source is a 390nm LED lamp with a power of 30W.

The temperature is 30-70°C, preferably 50°C.

The concentration of the nitrogen-containing heterocycle in the electrolyte is 0.01-0.1 mol/L, preferably 0.05 mol/L.

The molar ratio of the alkane to the nitrogen-containing heterocycle is (20-35):1, preferably 30:1.

The current density of the constant current was 2 mA/cm ² .

Advantages of the Invention

(1) The method of the present invention uses cheap cerium salt as a catalyst and cheap graphite felt and nickel foam as electrodes, so the reaction cost is low.

(2) The method of the present invention utilizes the synergistic effect of photoelectricity and uses clean electrons as oxidants to replace toxic and harmful chemical oxidants. The energy consumption and "three wastes" emissions of the reaction are low, which is in line with the concept of green chemistry and the "dual carbon" strategic needs.

(3) The method of the present invention can synthesize alkylated nitrogen-containing heterocyclic compounds with various substituent types, and has a wide range of substrate applicability.

(4) The method of the present invention realizes the first cerium salt-catalyzed coupling reaction of nitrogen-containing heterocycles and alkanes, which is highly innovative.

BRIEF DESCRIPTION OF THE DRAWINGS

Fig. 1 is a reaction flow chart of the present invention.

DETAILED DESCRIPTION

Unless otherwise specified, the experimental methods used in the following examples are conventional methods.

Unless otherwise specified, the materials and reagents used in the following examples can be obtained from commercial sources. The present invention is further described below in conjunction with the examples, but the present invention is not limited to the following examples.

Example 1: Photoelectrochemical synthesis of 1-cyclohexylisoquinoline

Add raw material isoquinoline (0.3mmol), cyclohexane (1mL), CeCl ₃ ·7H ₂ O (0.06mmol, 20mol%), n-Bu ₄ NCl (0.3mmol), CF ₃ COOH (1.2mmol) and MeOH (0.2mL) into a single-chamber electrolytic cell. Use acetonitrile:chlorobenzene = 2:1 (V/V, 6.0mL) as solvent, graphite felt (1.0×1.0cm ² ) as anode, and nickel foam (1.0×1.0cm ² ) as cathode. Place 390nm LEDs (30W) about 3.5cm from the reaction electrolytic cell. Stir and energize to provide light under 50℃ water bath conditions, current density is 2mA/cm ² , and TLC is used to detect the progress of the reaction. When TLC detects that the raw material isoquinoline disappears, stop irradiating and energizing, and the reaction is over. The reaction system was added with NaOH aqueous solution to make it alkaline, extracted with ethyl acetate (30 mL x 3), dried, and the solvent was distilled off under reduced pressure, and finally the target product was separated by column chromatography. 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 CNMR(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

In a single-chamber electrolytic cell, raw material methyl isoquinoline-3-carboxylate (0.3mmol), cyclohexane (1mL), CeCl ₃ ·7H ₂ O (0.06mmol, 20mol%), n-Bu ₄ NCl (0.3mmol), CF ₃ COOH (1.2mmol) and MeOH (0.2mL) were added respectively. Acetonitrile:chlorobenzene = 2:1 (V/V, 6.0mL) was used as the solvent, the anode was graphite felt (1.0×1.0cm ² ), and the cathode was nickel foam (1.0×1.0cm ² ). 390nm LEDs (30W) were placed about 3.5cm away from the reaction electrolytic cell. Stirring and energizing were performed under 50℃ water bath conditions to provide light, the current density was 2mA/cm ² , and the progress of the reaction was detected by TLC. When the raw material isoquinoline disappeared after TLC detection, the light and power were stopped, and the reaction was over. The reaction system was added with aqueous NaOH solution to make it alkaline, extracted with ethyl acetate (30 mL x 3), dried, and the solvent was removed by distillation under reduced pressure. Finally, the target product was separated by column chromatography. Yield: 44%.

Example 3: Photoelectrochemical synthesis of 1-cyclohexyl-4-cyanoisoquinoline

In a single-chamber electrolytic cell, raw material 4-cyanoisoquinoline (0.3mmol), cyclohexane (1mL), CeCl ₃ ·7H ₂ O (0.06mmol, 20mol%), n-Bu ₄ NCl (0.3mmol), CF ₃ COOH (1.2mmol) and MeOH (0.2mL) were added respectively. Acetonitrile:chlorobenzene = 2:1 (V/V, 6.0mL) was used as the solvent, the anode was graphite felt (1.0×1.0cm ² ), and the cathode was nickel foam (1.0×1.0cm ² ). 390nm LEDs (30W) were placed about 3.5cm away from the reaction electrolytic cell. Stirring and energizing were performed under 50℃ water bath conditions to provide light, the current density was 2mA/cm ² , and the progress of the reaction was detected by TLC. When the raw material isoquinoline disappeared after TLC detection, the light and power were stopped, and the reaction was over. The reaction system was added with aqueous NaOH solution to make it alkaline, extracted with ethyl acetate (30 mL x 3), dried, and the solvent was removed by distillation under reduced pressure. Finally, the target product was separated by column chromatography. Yield: 45%.

Example 4: Photoelectrochemical synthesis of 2-cyclohexyl-4-methylquinoline

In a single-chamber electrolytic cell, raw materials 4-methylquinoline (0.3mmol), cyclohexane (1mL), CeCl ₃ ·7H ₂ O (0.06mmol, 20mol%), n-Bu ₄ NCl (0.3mmol), CF ₃ COOH (1.2mmol) and MeOH (0.2mL) were added respectively. Acetonitrile:chlorobenzene = 2:1 (V/V, 6.0mL) was used as the solvent, the anode was graphite felt (1.0×1.0cm ² ), and the cathode was nickel foam (1.0×1.0cm ² ). 390nm LEDs (30W) were placed about 3.5cm away from the reaction electrolytic cell. Stirring and energizing were performed under 50℃ water bath conditions to provide light, the current density was 2mA/cm ² , and the progress of the reaction was detected by TLC. When the raw material isoquinoline disappeared after TLC detection, the light and power were stopped, and the reaction was over. The reaction system was added with NaOH aqueous solution to make it alkaline, extracted with ethyl acetate (30 mL x 3), dried, and the solvent was distilled off under reduced pressure, and finally the target product was separated by column chromatography. Yield: 65%.

Example 5: Photoelectrochemical synthesis of 2-cyclohexyl-4-methoxyquinoline

In a single-chamber electrolytic cell, raw materials 4-methoxyquinoline (0.3mmol), cyclohexane (1mL), CeCl ₃ ·7H ₂ O (0.06mmol, 20mol%), n-Bu ₄ NCl (0.3mmol), CF ₃ COOH (1.2mmol) and MeOH (0.2mL) were added respectively. Acetonitrile:chlorobenzene = 2:1 (V/V, 6.0mL) was used as the solvent, the anode was graphite felt (1.0×1.0cm ² ), and the cathode was nickel foam (1.0×1.0cm ² ). 390nm LEDs (30W) were placed about 3.5cm away from the reaction electrolytic cell. Stirring and energizing were performed under 50℃ water bath conditions to provide light, the current density was 2mA/cm ² , and the progress of the reaction was detected by TLC. When the raw material isoquinoline disappeared after TLC detection, the light and power were stopped, and the reaction was over. The reaction system was added with aqueous NaOH solution to make it alkaline, extracted with ethyl acetate (30 mL x 3), dried, and the solvent was distilled off under reduced pressure, and finally the target product was separated by column chromatography. Yield: 47%.

Example 6: Photoelectrochemical synthesis of 2-cyclohexyl-4-chloroquinoline

In a single-chamber electrolytic cell, raw materials 4-chloroquinoline (0.3mmol), cyclohexane (1mL), CeCl ₃ ·7H ₂ O (0.06mmol, 20mol%), n-Bu ₄ NCl (0.3mmol), CF ₃ COOH (1.2mmol) and MeOH (0.2mL) were added respectively. Acetonitrile: chlorobenzene = 2:1 (V/V, 6.0mL) was used as the solvent, the anode was graphite felt (1.0×1.0cm ² ), and the cathode was nickel foam (1.0×1.0cm ² ). 390nm LEDs (30W) were placed about 3.5cm away from the reaction electrolytic cell. Stirring and energizing were performed under 50℃ water bath conditions to provide light, the current density was 2mA/cm ² , and the progress of the reaction was detected by TLC. When the raw material isoquinoline disappeared after TLC detection, the light and power were stopped, and the reaction was over. The reaction system was added with aqueous NaOH solution to make it alkaline, extracted with ethyl acetate (30 mL x 3), dried, and the solvent was distilled off under reduced pressure, and finally the target product was separated by column chromatography. Yield: 47%.

Example 7: Photoelectrochemical synthesis of 2-cyclohexyl-4-chloro-6-methoxyquinoline

In a single-chamber electrolytic cell, raw materials 4-chloro-6-methoxyquinoline (0.3 mmol), cyclohexane (1 mL), CeCl ₃ ·7H ₂ O (0.06 mmol, 20 mol%), n-Bu ₄ NCl (0.3 mmol), CF ₃ COOH (1.2 mmol) and MeOH (0.2 mL) were added respectively. Acetonitrile:chlorobenzene = 2:1 (V/V, 6.0 mL) was used as the solvent, the anode was graphite felt (1.0×1.0 cm ² ), and the cathode was nickel foam (1.0×1.0 cm ² ). 390 nm LEDs (30 W) were placed about 3.5 cm from the reaction electrolytic cell. Under 50°C water bath conditions, the reaction was stirred and energized to provide light, the current density was 2 mA/cm ² , and the progress of the reaction was detected by TLC. When the raw material isoquinoline disappeared after TLC detection, the light and power were stopped, and the reaction was over. The reaction system was added with NaOH aqueous solution to make it alkaline, extracted with ethyl acetate (30 mL x 3), dried, and the solvent was removed by distillation under reduced pressure. Finally, the target product was separated by column chromatography. Yield: 40%

Example 8: Photoelectrochemical synthesis of 2-cyclohexyl-4-chloro-6,7-dimethoxyquinoline

In a single-chamber electrolytic cell, raw materials 4-chloro-6,7-dimethoxyquinoline (0.3mmol), cyclohexane (1mL), CeCl ₃ ·7H ₂ O (0.06mmol, 20mol%), n-Bu ₄ NCl (0.3mmol), CF ₃ COOH (1.2mmol) and MeOH (0.2mL) were added respectively. Acetonitrile:chlorobenzene = 2:1 (V/V, 6.0mL) was used as the solvent, the anode was graphite felt (1.0×1.0cm ² ), and the cathode was nickel foam (1.0×1.0cm ² ). 390nm LEDs (30W) were placed about 3.5cm away from the reaction electrolytic cell. Stirring and energizing were performed under 50℃ water bath conditions to provide light, and the current density was 2mA/cm ² . The progress of the reaction was detected by TLC. When the raw material isoquinoline disappeared after TLC detection, the light and power were stopped, and the reaction was over. The reaction system was added with NaOH aqueous solution to make it alkaline, extracted with ethyl acetate (30 mL x 3), dried, and the solvent was removed by distillation under reduced pressure, and finally the target product was separated by column chromatography. Yield: 64%.

Example 9: Photoelectrochemical synthesis of 2-cyclohexyl-4-phenylquinoline

In a single-chamber electrolytic cell, raw materials 4-phenylquinoline (0.3mmol), cyclohexane (1mL), CeCl ₃ ·7H ₂ O (0.06mmol, 20mol%), n-Bu ₄ NCl (0.3mmol), CF ₃ COOH (1.2mmol) and MeOH (0.2mL) were added respectively. Acetonitrile:chlorobenzene = 2:1 (V/V, 6.0mL) was used as the solvent, the anode was graphite felt (1.0×1.0cm ² ), and the cathode was nickel foam (1.0×1.0cm ² ). 390nm LEDs (30W) were placed about 3.5cm away from the reaction electrolytic cell. Stirring and energizing were performed under 50℃ water bath conditions to provide light, the current density was 2mA/cm ² , and the progress of the reaction was detected by TLC. When the raw material isoquinoline disappeared after TLC detection, the light and power were stopped, and the reaction was over. The reaction system was added with NaOH aqueous solution to make it alkaline, extracted with ethyl acetate (30 mL x 3), dried, and the solvent was distilled off under reduced pressure, and finally the target product was separated by column chromatography. Yield: 73%.

Example 10: Photoelectrochemical synthesis of 2-cyclohexyl-4-(4-methylphenyl)quinoline

In a single-chamber electrolytic cell, raw materials 4-(4-methylphenyl)quinoline (0.3mmol), cyclohexane (1mL), CeCl ₃ ·7H ₂ O (0.06mmol, 20mol%), n-Bu ₄ NCl (0.3mmol), CF ₃ COOH (1.2mmol) and MeOH (0.2mL) were added respectively. Acetonitrile:chlorobenzene = 2:1 (V/V, 6.0mL) was used as the solvent, the anode was graphite felt (1.0×1.0cm ² ), and the cathode was nickel foam (1.0×1.0cm ² ). 390nm LEDs (30W) were placed about 3.5cm away from the reaction electrolytic cell. Under 50℃ water bath conditions, the reaction was stirred and energized to provide light, the current density was 2mA/cm ² , and the progress of the reaction was detected by TLC. When the raw material isoquinoline disappeared after TLC detection, the light and power were stopped, and the reaction was over. The reaction system was added with aqueous NaOH solution to make it alkaline, extracted with ethyl acetate (30 mL x 3), dried, and the solvent was removed by distillation under reduced pressure. Finally, the target product was separated by column chromatography. Yield: 63%.

Example 11: Photoelectrochemical synthesis of 2-cyclohexyl-4-(4-tert-butylphenyl)quinoline

In a single-chamber electrolytic cell, raw materials 4-(4-tert-butylphenyl)quinoline (0.3mmol), cyclohexane (1mL), CeCl ₃ ·7H ₂ O (0.06mmol, 20mol%), n-Bu ₄ NCl (0.3mmol), CF ₃ COOH (1.2mmol) and MeOH (0.2mL) were added respectively. Acetonitrile:chlorobenzene = 2:1 (V/V, 6.0mL) was used as the solvent, the anode was graphite felt (1.0×1.0cm ² ), and the cathode was nickel foam (1.0×1.0cm ² ). 390nm LEDs (30W) were placed about 3.5cm away from the reaction electrolytic cell. Stirring and energizing were performed under 50℃ water bath conditions to provide light, the current density was 2mA/cm ² , and the progress of the reaction was detected by TLC. When the raw material isoquinoline disappeared after TLC detection, the light irradiation and power supply were stopped, and the reaction was completed. The reaction system was added with NaOH aqueous solution to make it alkaline, extracted with ethyl acetate (30 mL x 3), dried, and the solvent was removed by distillation under reduced pressure, and finally the target product was separated by column chromatography. Yield: 71%.

Example 12: Photoelectrochemical synthesis of 2-cyclohexyl-4-(3-biphenyl)quinoline

In a single-chamber electrolytic cell, raw materials 4-(3-biphenyl)quinoline (0.3mmol), cyclohexane (1mL), CeCl ₃ ·7H ₂ O (0.06mmol, 20mol%), n-Bu ₄ NCl (0.3mmol), CF ₃ COOH (1.2mmol) and MeOH (0.2mL) were added respectively. Acetonitrile:chlorobenzene = 2:1 (V/V, 6.0mL) was used as the solvent, the anode was graphite felt (1.0×1.0cm ² ), and the cathode was nickel foam (1.0×1.0cm ² ). 390nm LEDs (30W) were placed about 3.5cm away from the reaction electrolytic cell. Stirring and energizing were performed under 50℃ water bath conditions to provide light, the current density was 2mA/cm ² , and the progress of the reaction was detected by TLC. When the raw material isoquinoline disappeared after TLC detection, the light irradiation and power supply were stopped, and the reaction was completed. The reaction system was added with aqueous NaOH solution to make it alkaline, extracted with ethyl acetate (30 mL x 3), dried, and the solvent was removed by distillation under reduced pressure, and finally the target product was separated by column chromatography. Yield: 77%.

Example 13: Photoelectrochemical synthesis of 3-cyclohexyl-N-methylquinoxalinone

In a single-chamber electrolytic cell, raw materials N-methylquinoxalinone (0.3mmol), cyclohexane (1mL), CeCl ₃ ·7H ₂ O (0.06mmol, 20mol%), n-Bu ₄ NCl (0.3mmol), CF ₃ COOH (1.2mmol) and MeOH (0.2mL) were added respectively. Acetonitrile:chlorobenzene = 2:1 (V/V, 6.0mL) was used as the solvent, the anode was graphite felt (1.0×1.0cm ² ), and the cathode was nickel foam (1.0×1.0cm ² ). 390nm LEDs (30W) were placed about 3.5cm away from the reaction electrolytic cell. Stirring and energizing were performed under 50℃ water bath conditions to provide light, and the current density was 2mA/cm ² . The progress of the reaction was detected by TLC. When the raw material isoquinoline disappeared after TLC detection, the light and power were stopped, and the reaction was over. The reaction system was added with NaOH aqueous solution to make it alkaline, extracted with ethyl acetate (30 mL x 3), dried, and the solvent was distilled off under reduced pressure, and finally the target product was separated by column chromatography. Yield: 66%.

Example 14: Photoelectrochemical synthesis of 3-cyclohexyl-N-benzylquinoxalinone

In a single-chamber electrolytic cell, raw materials N-benzylquinoxalinone (0.3mmol), cyclohexane (1mL), CeCl ₃ ·7H ₂ O (0.06mmol, 20mol%), n-Bu ₄ NCl (0.3mmol), CF ₃ COOH (1.2mmol) and MeOH (0.2mL) were added respectively. Acetonitrile:chlorobenzene = 2:1 (V/V, 6.0mL) was used as the solvent, the anode was graphite felt (1.0×1.0cm ² ), and the cathode was nickel foam (1.0×1.0cm ² ). 390nm LEDs (30W) were placed about 3.5cm away from the reaction electrolytic cell. Stirring and energizing were performed under 50℃ water bath conditions to provide light, the current density was 2mA/cm ² , and the progress of the reaction was detected by TLC. When the raw material isoquinoline disappeared after TLC detection, the light and power were stopped, and the reaction was over. The reaction system was added with aqueous NaOH solution to make it alkaline, extracted with ethyl acetate (30 mL x 3), dried, and the solvent was removed by distillation under reduced pressure, and finally the target product was separated by column chromatography. Yield: 51%.

Example 15: Photoelectrochemical synthesis of ethyl 2-(3-cyclohexyl-2-quinoxalinone)acetate

In a single-chamber electrolytic cell, raw materials ethyl 2-(2-quinoxalinone)acetate (0.3mmol), cyclohexane (1mL), CeCl ₃ ·7H ₂ O (0.06mmol, 20mol%), n-Bu ₄ NCl (0.3mmol), CF ₃ COOH (1.2mmol) and MeOH (0.2mL) were added respectively. Acetonitrile:chlorobenzene = 2:1 (V/V, 6.0mL) was used as the solvent, the anode was graphite felt (1.0×1.0cm ² ), and the cathode was nickel foam (1.0×1.0cm ² ). 390nm LEDs (30W) were placed about 3.5cm away from the reaction electrolytic cell. Stirring and energizing were performed under 50℃ water bath conditions to provide light, the current density was 2mA/cm ² , and the progress of the reaction was detected by TLC. When the raw material isoquinoline disappeared after TLC detection, the light and power were stopped, and the reaction was over. The reaction system was added with NaOH aqueous solution to make it alkaline, extracted with ethyl acetate (30 mL x 3), dried, and the solvent was distilled off under reduced pressure, and finally the target product was separated by column chromatography. Yield: 72%.

Example 16: Photoelectrochemical synthesis of 2-cyclohexyl-4-phenylpyridine

In a single-chamber electrolytic cell, raw materials 4-phenylpyridine (0.3mmol), cyclohexane (1mL), CeCl ₃ ·7H ₂ O (0.06mmol, 20mol%), n-Bu ₄ NCl (0.3mmol), CF ₃ COOH (1.2mmol) and MeOH (0.2mL) were added respectively. Acetonitrile:chlorobenzene = 2:1 (V/V, 6.0mL) was used as the solvent, the anode was graphite felt (1.0×1.0cm ² ), and the cathode was nickel foam (1.0×1.0cm ² ). 390nm LEDs (30W) were placed about 3.5cm away from the reaction electrolytic cell. Stirring and energizing were performed under 50℃ water bath conditions to provide light, the current density was 2mA/cm ² , and the progress of the reaction was detected by TLC. When the raw material isoquinoline disappeared after TLC detection, the light and power were stopped, and the reaction was over. The reaction system was added with NaOH aqueous solution to make it alkaline, extracted with ethyl acetate (30 mL x 3), dried, and the solvent was removed by distillation under reduced pressure. Finally, the target product was separated by column chromatography. Yield: 58%.

Example 17: Photoelectrochemical synthesis of 6-cyclohexylphenanthridine

In a single-chamber electrolytic cell, raw materials phenanthridine (0.3 mmol), cyclohexane (1 mL), CeCl ₃ ·7H ₂ O (0.06 mmol, 20 mol%), n-Bu ₄ NCl (0.3 mmol), CF ₃ COOH (1.2 mmol) and MeOH (0.2 mL) were added respectively. Acetonitrile:chlorobenzene = 2:1 (V/V, 6.0 mL) was used as the solvent, the anode was graphite felt (1.0×1.0 cm ² ), and the cathode was nickel foam (1.0×1.0 cm ² ). 390 nm LEDs (30 W) were placed about 3.5 cm from the reaction electrolytic cell. Stirring and energizing were performed in a 50°C water bath to provide light, and the current density was 2 mA/cm ^{2 .} The progress of the reaction was detected by TLC. When the raw material isoquinoline disappeared as detected by TLC, the light and power were stopped, and the reaction was completed. The reaction system was added with NaOH aqueous solution to make it alkaline, extracted with ethyl acetate (30 mL x 3), dried, and the solvent was removed by distillation under reduced pressure, and finally the target product was separated by column chromatography. Yield: 89%.

Example 18: Photoelectrochemical synthesis of 2-cyclohexylbenzothiazole

Add raw materials benzothiazole (0.3mmol), cyclohexane (1mL), CeCl ₃ ·7H ₂ O (0.06mmol, 20mol%), n-Bu ₄ NCl (0.3mmol), CF ₃ COOH (1.2mmol) and MeOH (0.2mL) into a single-chamber electrolytic cell. Use acetonitrile:chlorobenzene = 2:1 (V/V, 6.0mL) as solvent, graphite felt (1.0×1.0cm ² ) as anode, and nickel foam (1.0×1.0cm ² ) as cathode. Place 390nm LEDs (30W) about 3.5cm from the reaction electrolytic cell. Stir and energize to provide light under 50℃ water bath conditions, current density is 2mA/cm ² , and TLC is used to detect the progress of the reaction. When TLC detects that the raw material isoquinoline disappears, stop irradiating and energizing, and the reaction is over. The reaction system was added with NaOH aqueous solution to make it alkaline, extracted with ethyl acetate (30 mL x 3), dried, and the solvent was distilled off under reduced pressure, and finally the target product was separated by column chromatography. Yield: 40%.

Example 19: Photoelectrochemical synthesis of 1-cyclopentylisoquinoline

Add raw material isoquinoline (0.3mmol), cyclopentane (1mL), CeCl ₃ ·7H ₂ O (0.06mmol, 20mol%), n-Bu ₄ NCl (0.3mmol), CF ₃ COOH (1.2mmol) and MeOH (0.2mL) into a single-chamber electrolytic cell. Use acetonitrile:chlorobenzene = 2:1 (V/V, 6.0mL) as solvent, graphite felt (1.0×1.0cm ² ) as anode, and nickel foam (1.0×1.0cm ² ) as cathode. Place 390nm LEDs (30W) about 3.5cm from the reaction electrolytic cell. Stir and energize to provide light under 50℃ water bath conditions, current density is 2mA/cm ² , and TLC is used to detect the progress of the reaction. When TLC detects that the raw material isoquinoline disappears, stop irradiating and energizing, and the reaction is over. The reaction system was added with NaOH aqueous solution to make it alkaline, extracted with ethyl acetate (30 mL x 3), dried, and the solvent was distilled off under reduced pressure, and finally the target product was separated by column chromatography. Yield: 65%.

Example 20: Photoelectrochemical synthesis of 1-cycloheptylisoquinoline

Add raw material isoquinoline (0.3mmol), cycloheptane (1mL), CeCl ₃ ·7H ₂ O (0.06mmol, 20mol%), n-Bu ₄ NCl (0.3mmol), CF ₃ COOH (1.2mmol) and MeOH (0.2mL) into a single-chamber electrolytic cell. Use acetonitrile:chlorobenzene = 2:1 (V/V, 6.0mL) as solvent, graphite felt (1.0×1.0cm ² ) as anode, and nickel foam (1.0×1.0cm ² ) as cathode. Place 390nm LEDs (30W) about 3.5cm from the reaction electrolytic cell. Stir and energize to provide light under 50℃ water bath conditions, current density is 2mA/cm ² , and TLC is used to detect the progress of the reaction. When TLC detects that raw material isoquinoline disappears, stop irradiating and energizing, and the reaction is over. The reaction system was added with NaOH aqueous solution to make it alkaline, extracted with ethyl acetate (30 mL x 3), dried, and the solvent was distilled off under reduced pressure, and finally the target product was separated by column chromatography. Yield: 89%.

Example 21: Photoelectrochemical synthesis of 1-cyclooctylisoquinoline

Add raw material isoquinoline (0.3mmol), cyclooctane (1mL), CeCl ₃ ·7H ₂ O (0.06mmol, 20mol%), n-Bu ₄ NCl (0.3mmol), CF ₃ COOH (1.2mmol) and MeOH (0.2mL) into a single-chamber electrolytic cell. Use acetonitrile:chlorobenzene = 2:1 (V/V, 6.0mL) as solvent, graphite felt (1.0×1.0cm ² ) as anode, and nickel foam (1.0×1.0cm ² ) as cathode. Place 390nm LEDs (30W) about 3.5cm from the reaction electrolytic cell. Stir and energize to give light under 50℃ water bath condition, current density is 2mA/cm ² , and TLC is used to detect the progress of the reaction. When TLC detects that raw material isoquinoline disappears, stop irradiating and energizing, and the reaction is over. The reaction system was added with NaOH aqueous solution to make it alkaline, extracted with ethyl acetate (30 mL x 3), dried, and the solvent was distilled off under reduced pressure, and finally the target product was separated by column chromatography. Yield: 56%.

Example 22: Photoelectrochemical synthesis of 1-cyclododecylisoquinoline

Add raw material isoquinoline (0.3mmol), cyclododecane (1mL), CeCl ₃ ·7H ₂ O (0.06mmol, 20mol%), n-Bu ₄ NCl (0.3mmol), CF ₃ COOH (1.2mmol) and MeOH (0.2mL) into a single-chamber electrolytic cell. Use acetonitrile:chlorobenzene = 2:1 (V/V, 6.0mL) as solvent, graphite felt (1.0×1.0cm ² ) as anode, and nickel foam (1.0×1.0cm ² ) as cathode. Place 390nm LEDs (30W) about 3.5cm away from the reaction electrolytic cell. Stir and energize to provide light under 50℃ water bath conditions, current density is 2mA/cm ² , and TLC is used to detect the progress of the reaction. When TLC detects that the raw material isoquinoline disappears, stop irradiating and energizing, and the reaction is over. The reaction system was added with NaOH aqueous solution to make it alkaline, extracted with ethyl acetate (30 mL x 3), dried, and the solvent was distilled off under reduced pressure, and finally the target product was separated by column chromatography. Yield: 63%.

Example 23: Photoelectrochemical synthesis of 1-(2-norbornyl)isoquinoline

In a single-chamber electrolytic cell, raw materials of isoquinoline (0.3 mmol), norbornane (15 equiv), CeCl ₃ ·7H ₂ O (0.06 mmol, 20 mol%), n-Bu ₄ NCl (0.3 mmol), CF ₃ COOH (1.2 mmol) and MeOH (0.2 mL) were added respectively. Acetonitrile:chlorobenzene = 2:1 (V/V, 6.0 mL) was used as the solvent, the anode was graphite felt (1.0×1.0 cm ² ), and the cathode was nickel foam (1.0×1.0 cm ² ). 390 nm LEDs (30 W) were placed about 3.5 cm from the reaction electrolytic cell. Under the condition of 50°C water bath, the reaction was stirred and energized to provide light, the current density was 2 mA/cm ² , and the progress of the reaction was detected by TLC. When the raw material isoquinoline disappeared after TLC detection, the light and power were stopped, and the reaction was over. The reaction system was added with NaOH aqueous solution to make it alkaline, extracted with ethyl acetate (30 mL x 3), dried, and the solvent was removed by distillation under reduced pressure, and finally the target product was separated by column chromatography. Yield: 61%.

Example 24: Photoelectrochemical synthesis of 1-(2-n-pentyl)isoquinoline and 1-(3-n-pentyl)isoquinoline

Add raw material isoquinoline (0.3mmol), n-pentane (1mL), CeCl ₃ ·7H ₂ O (0.06mmol, 20mol%), n-Bu ₄ NCl (0.3mmol), CF ₃ COOH (1.2mmol) and MeOH (0.2mL) into a single-chamber electrolytic cell. Use acetonitrile:chlorobenzene = 2:1 (V/V, 6.0mL) as solvent, graphite felt (1.0×1.0cm ² ) as anode, and nickel foam (1.0×1.0cm ² ) as cathode. Place 390nm LEDs (30W) about 3.5cm from the reaction electrolytic cell. Stir and energize to give light under 50℃ water bath condition, current density is 2mA/cm ² , and TLC is used to detect the progress of the reaction. When TLC detects that raw material isoquinoline disappears, stop irradiating and energizing, and the reaction is over. The reaction system was added with NaOH aqueous solution to make it alkaline, extracted with ethyl acetate (30 mL x 3), dried, and the solvent was removed by distillation under reduced pressure. Finally, the target product was separated by column chromatography. Yield: 62%.

Example 25: Photoelectrochemical synthesis of 1-(2-n-hexyl)isoquinoline and 1-(3-n-hexyl)isoquinoline

Add raw material isoquinoline (0.3mmol), n-hexane (1mL), CeCl ₃ ·7H ₂ O (0.06mmol, 20mol%), n-Bu ₄ NCl (0.3mmol), CF ₃ COOH (1.2mmol) and MeOH (0.2mL) into a single-chamber electrolytic cell. Use acetonitrile:chlorobenzene = 2:1 (V/V, 6.0mL) as solvent, graphite felt (1.0×1.0cm ² ) as anode, and nickel foam (1.0×1.0cm ² ) as cathode. Place 390nm LEDs (30W) about 3.5cm away from the reaction electrolytic cell. Stir and energize to provide light under 50℃ water bath conditions, current density is 2mA/cm ² , and TLC is used to detect the progress of the reaction. When TLC detects that raw material isoquinoline disappears, stop irradiating and energizing, and the reaction is over. The reaction system was added with NaOH aqueous solution to make it alkaline, extracted with ethyl acetate (30 mL x 3), dried, and the solvent was removed by distillation under reduced pressure. Finally, the target product was separated by column chromatography. Yield: 58%.

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 。