CN109988117B - Preparation method of a class of 3-methylquinoxaline-2(1H)-one derivatives - Google Patents

Abstract

The invention discloses a method for preparing a 3-methylquinoxaline-2(1H)-ketone compound. The method comprises the following steps of performing a visible light catalytic reaction between a quinoxalinone compound and iodobenzene diacetate under the action of a photocatalyst , that is, 3-methylquinoxalinone compounds are obtained; relative to the prior art, the synthetic method has the following advantages: 1) the quinoxaline-2(1H)-ketone derivative raw materials used are cheap and easy to obtain, which is conducive to reducing cost, 2) the reaction can be carried out by light at room temperature, the conditions are mild, and the product can be obtained in one step, the reaction yield is high, the operation is environmentally friendly, which is beneficial to industrial production, 3) the method has good applicability to functional groups, and can obtain various 3 - Methylquinoxalinone derivatives.

Description

Preparation method of a class of 3-methylquinoxaline-2(1H)-one derivatives

technical field

The invention relates to a method for synthesizing quinoxalinone derivatives, in particular to a method for synthesizing quinoxalin-2(1H)-one compounds and iodobenzene diacetate as starting materials, under the action of a photocatalyst, through photocatalysis A method for preparing 3-methylquinoxalin-2(1H)-one in one step belongs to the technical field of organic synthesis.

Background technique

Methyl group is the smallest alkyl fragment, which is present in most drug molecules. The introduction of methyl group into the molecule can improve the drug solubility, selectivity and metabolic activity of drug molecules. Introducing a methyl group at the vicinal position of the metabolic site creates steric hindrance, which can prolong the half-life of the drug, such as simvastatin. If the half-life of the drug is too long, medicinal chemists can also introduce a methyl group to generate a new metabolic site to shorten the drug. Half-life, like etoricoxib, the effect of methyl in medicinal chemistry is known as the "magic methyl effect".

As an important class of nitrogen heterocyclic derivatives, quinoxalin-2(1H)-ones have been widely used in natural products, pharmacy and materials science. Among them, 3-methylquinoxaline-2(1H) )-ketone derivatives have attracted the interest of a large number of organic chemistry researchers because of their ability to control the biological activity of quinoxalinone. For example, compound A is a c-met kinase inhibitor (Bioorg. Med. Chem. 2015, 23, 6560), and the introduction of methyl groups significantly improved the drug activity of the molecule.

At present, there are relevant reports on the arylation, acylation, phosphorylation, amination and trifluoromethylation of the C3 position of quinoxaline-2(1H)-one. - The direct methylation of the C3 position of ketone compounds has not been reported yet.

SUMMARY OF THE INVENTION

Aiming at the technical gap existing in the prior art for the C3 alkylation reaction of p-quinoxalin-2(1H)-one, the object of the present invention is to provide a kind of photocatalytic reaction to realize 3-methyl group under mild conditions A method for synthesizing quinoxalin-2(1H)-one and its derivatives, the method avoids the use of metal catalysts that pollute the environment by using photocatalysts, and at the same time reacts under mild conditions such as light at room temperature, avoiding high temperature and other complicated It can reduce the cost and energy consumption of the reaction, improve the efficiency of the reaction and achieve the purpose of greening chemistry.

In order to achieve the above technical purpose, the present invention provides a preparation method of a 3-methylquinoxaline-2(1H)-one compound, the quinoxalinone compound of formula 1 and the iodobenzene diacetate of formula 2 and a light Under the action of a catalyst, a visible light catalytic reaction is carried out to obtain a 3-methylquinoxalinone compound of formula 3;

in,

R ₁ is hydrogen, alkyl or aralkyl;

R2 and _R3 are independently selected from _hydrogen , alkyl, alkoxy, nitro, amino, acyl, halogen substituent, hydroxy, cyano or trifluoromethyl.

In the compounds of formula 1, formula 2 and formula 3 of the present invention. R ₁ is a group substituted on a nitrogen atom, which can be selected to be a hydrogen atom, or other groups to replace the hydrogen atom, such as alkyl or aralkyl to replace the hydrogen. The alkyl group is a C ₁ -C ₈ alkyl group, which can be a straight-chain alkyl group or a branched-chain alkyl group, or a cyclic alkyl group, such as methyl, ethyl, butyl, isopropyl, and cyclohexyl. and many more. Aralkyl is mainly an aryl group substituted on the alkyl chain of an alkyl group, the length of the alkyl chain is C ₁ -C ₈ , and an aryl group is substituted on any carbon atom of the alkyl chain, such as phenyl and naphthyl. Or substituted phenyl, substituted phenyl contains some conventional substituents on the benzene ring, such as C ₁ -C ₅ alkyl, C ₁ -C ₅ alkoxy, halogen substituents, etc., the most common aralkyl Such as benzyl, phenylethyl and the like. R ₂ and R ₃ are substituent groups contained on the benzene ring of quinoxalinone compounds, R ₂ and R ₃ have relatively little effect on the alkylation reaction of quinoxalinone compounds at C3 position, and their substitution positions can be Any position that can be substituted on the benzene ring, and its selection range is wide, such as hydrogen, alkyl, alkoxy, nitro, amino, acyl, halogen substituent, hydroxyl, cyano or trifluoromethyl, etc., when R When ₂ or R ₃ selects an alkyl group, the alkyl group is a C ₁ -C ₈ alkyl group, which can be a straight-chain alkyl group or a branched-chain alkyl group, or a cyclic alkyl group, such as methyl, ethyl , butyl, isopropyl, cyclohexyl, etc.; when R ₂ or R ₃ selects an alkoxy group, the alkoxy group is a C ₁ -C ₈ alkoxy group, such as methoxy, ethoxy, isobutoxy When R ₂ or R ₃ selects an acyl group, the acyl group is formyl, acetyl or propionyl; when R ₂ or R ₃ selects a halogen substituent, the halogen substituent is fluorine, chlorine, bromine or iodine.

In a preferred solution, the molar ratio of the quinoxalin-2-one derivatives to iodobenzene diacetate is 1:1 to 1:20. More preferably, it is 1:1 to 1:10.

In a preferred solution, the molar ratio of the quinoxalin-2-one derivatives to the photocatalyst is: 1:0.01-1:0.05.

In a more preferred solution, the photocatalyst includes Ru(bpy) ₃ Cl ₂ , eosin B (C ₂₀ H ₆ Br ₂ N ₂ Na ₂ O ₉ ), water-soluble eosin (eosin Y, C ₂₀ H ₆ Br _{4 )} At least one of Na ₃ O ₅ ), alcohol-soluble eosin, rhodamine B, and food coloring red. _The most preferred photocatalyst is Ru(bpy) _3Cl2 .

In a preferred solution, the conditions for the visible light catalytic reaction are: under visible light irradiation, the reaction is performed at room temperature for 6 to 12 hours.

In a preferred solution, the visible light source is an LED white light source, a blue light source or a green light source with a power of 3W to 24W. A more preferred visible light source is an LED white light source with a power of 12W.

In a preferred solution, the photocatalytic reaction is carried out in at least one reaction medium among DMSO, DMF, CHCl ₃ , CH ₃ OH, PEG-200, and PEG-400. A more preferred reaction medium is PEG-200.

The synthetic route of the 3-methylquinoline-2(1H)-one compound of the present invention is as follows:

The synthesis reaction mechanism of the 3-methylquinoxaline-2(1H)-one compounds of the present invention is as follows: the photocatalyst is activated by light to release electrons, the released electrons are captured by iodobenzene diacetate, and the captured electron iodobenzene diacetate The methyl radical is released by cleavage, and the methyl radical attacks the 3-position carbon of quinoxalinones to form intermediate A, which is converted into unstable intermediate B by recapturing electrons by the photocatalyst, and intermediate B occurs Intramolecular recombination and release of hydrogen protons yield the target compound.

Relative to the prior art, the beneficial technical effects brought by the technical solution of the present invention:

The present invention avoids the use of metal catalysts that pollute the environment by using green and environment-friendly photocatalysts.

The quinoxalinone compound C3 methylation reaction efficiency of the present invention is high, and high selectivity yield can be obtained.

The reaction conditions of the invention are mild, and the reaction can be carried out under mild conditions such as normal temperature and illumination, avoiding high temperature and other complicated operations, and reducing the reaction cost and energy consumption.

The invention has good applicability to functional groups, can obtain various 3-methylquinoxalinone compound derivatives, and provides a brand-new route for the synthesis of quinoxalinone compound derivatives.

Detailed ways

The following examples are intended to further illustrate the content of the present invention, rather than limit the protection scope of the claims of the present invention.

Condition optimization experiment:

The specific reaction conditions are as follows: at 25 ° C, in a 10 mL reaction tube, add compound 1a (0.2 mmol), iodobenzene diacetate 2a (0.44 mmol), photocatalyst, solvent (1 mL), mix well, and then in Under the irradiation of 12w white LED lamp, the reaction was stirred for 8h. After the reaction was detected by TLC, cyclopentyl methyl ether (2ml×3) was added for extraction, and the upper layer extract was taken and concentrated in vacuo to no solvent at 50°C to obtain a crude product, which was then used with petroleum ether in a volume ratio of 2:1. Rinse with mixed eluent with ethyl acetate, and perform flash column chromatography on silica gel to obtain product 3aa.

In order to obtain 3-methyl-2(1H)-quinoxalinone compounds in high yield, the following control experiment groups 1 to 13 were carried out according to the above reaction conditions, and some conditional factors affecting the reaction were investigated, mainly including the photocatalyst Types, solvents, and the specific optimization process are shown in the following table:

It can be seen from the above table that among all the photocatalysts used in the experiments, Ru(bpy) ₃ Cl ₂ , eosin B, water-soluble eosin and other photocatalysts can achieve 3-methyl-2(1H)-quinoxaline Synthesis of ketones, but Ru(bpy _{) 3Cl2} has the best catalytic effect. And the amount of the catalyst is about 1% to achieve a good catalytic effect. For the choice of solvent, the best solvent is PEG-200; secondly, DMF and DMSO are also good solvents for reaction, while acetonitrile, tetrahydrofuran and dichloroethane can hardly obtain the target product.

The following specific implementation cases 1 to 12 are all reacted under optimized conditions, and the influence of different substituent groups on the reaction is investigated.

Example 1

At 25°C, in a 10 mL reaction tube, sequentially add 1-methylquinoxalin-2(1H)-one 1a (0.2 mmol), iodobenzene diacetate 2a (0.44 mmol), Ru(bpy) ₃ Cl ₂ · 6H ₂ O (0.002 mmol), PEG-200 (1 mL), mixed well, and then stirred for 8 h under the irradiation of a 12w white LED lamp. After the reaction was detected by TLC, cyclopentyl methyl ether (2ml×3) was added for extraction, and the upper layer extract was taken and concentrated in vacuo to no solvent at 50°C to obtain a crude product, which was then used with petroleum ether in a volume ratio of 2:1. The 1,3-dimethylquinoxalin-2(1H)-one product 3aa in this example was obtained as a white solid, 32.8 mg in a yield of 32.8 mg. 91%.

The nuclear magnetic spectrum data of the obtained product are: ¹ H NMR (400MHz, CDCl ₃ ): δ=7.80(d, J=8.0Hz, 1H), 7.54-7.50(m, 1H), 7.35-7.29(m, 2H), 3.70 (s, 3H), 2.60 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ): δ=158.4, 155.2, 133.2, 132.6, 129.6, 129.4, 123.6, 113.6, 29.0, 21.6.

Example 2

At 25°C, in a 10 mL reaction tube, sequentially add 6-bromo-1-methylquinoxalin-2(1H)-one 1b (0.2 mmol), iodobenzene diacetate 2a (0.44 mmol), Ru (bpy ) ₃ Cl ₂ ·6H ₂ O (0.002 mmol), PEG-200 (1 mL), mixed uniformly, and then stirred for 8 h under the irradiation of a 12W white LED lamp. After the reaction was detected by TLC, cyclopentyl methyl ether (2ml×3) was added for extraction, and the upper layer extract was taken and concentrated in vacuo to no solvent at 50°C to obtain a crude product, which was then used with petroleum ether in a volume ratio of 2:1. Rinse with ethyl acetate mixed eluent, and perform flash column chromatography on silica gel to obtain 6-bromo-1,3-dimethylquinoxalin-2(1H)-one product 3ba in this example, which is a white solid 42.8 mg, the yield is 85%.

The nuclear magnetic spectrum data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ): δ=7.94 (d, J=2.0 Hz, 1H), 7.60 (dd, J ₁ =8.8 Hz, J ₂ =2.0 Hz, 1H), 7.16 (d, J=8.8 Hz, 1H), 3.67 (s, 3H), 2.59 (s, 3H); ¹³ CNMR (100 MHz, CDCl ₃ ): δ=159.8, 154.8, 133.5, 132.4, 132.3, 131.9, 116.1 , 115.0, 29.2, 21.7.

The high-resolution mass spectrum data of the obtained product are: HRMS calc.for r C ₁₀ H ₁₀ BrN ₂ O[M+H] ⁺ : 252.9971, found 252.9968.

Example 3

In a 10 mL reaction tube at 25°C, 7-fluoro-1-methylquinoxalin-2(1H)-one 1c (0.2 mmol), iodobenzene diacetate 2a (0.44 mmol), Ru (bpy ) ₃ Cl ₂ ·6H ₂ O (0.002 mmol), PEG-200 (1 mL), mixed uniformly, and then stirred for 6 h under the irradiation of a 12W white LED lamp. After the reaction was detected by TLC, cyclopentyl methyl ether (2ml×3) was added for extraction, and the upper layer extract was taken and concentrated in vacuo to no solvent at 50°C to obtain a crude product, which was then used with petroleum ether in a volume ratio of 2:1. Rinse with ethyl acetate mixed eluent, and perform flash column chromatography on silica gel to obtain the 7-fluoro-1,3-dimethylquinoxalin-2(1H)-one product 3ca in this example, which is a white solid 35.3 mg, the yield is 92%.

The nuclear magnetic spectrum data of the obtained product are: ¹ H NMR (400MHz, CDCl ₃ ): δ=7.79-7.76 (m, 1H), 7.07-7.02 (m, 1H), 6.98 (dd, J ₁ =10.0Hz, J ₂ = 2.4Hz, 1H), 3.66(s, 3H), 2.57(s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ): δ=164.1, 161.6, 157.2, 155.1, 134.7, 134.6, 131.3, 131.2, 129.4, , 111.5, 111.2, 100.7, 100.4, 29.3, 21.4; ¹⁹ F NMR (376MHz, CDCl ₃ ): δ=-108.3.

The high-resolution mass spectrum data of the obtained product are: HRMS (ESI) m/z calcd.for C ₁₀ H ₁₀ FN ₂ O[M+H] ⁺ : 193.0772, found 193.0770.

Example 4

In a 10 mL reaction tube at 25°C, 6-nitro-1-methylquinoxalin-2(1H)-one 1d (0.2 mmol), iodobenzene diacetate 2a (0.44 mmol), Ru ( bpy) ₃ Cl ₂ ·6H ₂ O (0.002 mmol), PEG-200 (1 mL), mixed uniformly, and then stirred for 8 h under the irradiation of a 12W white LED lamp. After the reaction was detected by TLC, cyclopentyl methyl ether (2ml×3) was added for extraction, and the upper layer extract was taken and concentrated in vacuo to no solvent at 50°C to obtain a crude product, which was then used with petroleum ether in a volume ratio of 2:1. Rinse with ethyl acetate mixed eluent, silica gel column flash column chromatography to obtain 6-nitro-1,3-dimethylquinoxalin-2(1H)-one product 3da in this example as a yellow solid 36.8 mg, yield 84%.

The nuclear magnetic spectrum data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ): δ=8.69 (d, J=2.4 Hz, 1H), 8.38 (dd, J ₁ =9.2 Hz, J ₂ =2.4 Hz, 1H), 7.39 (d, J=9.2 Hz, 1H), 3.75 (s, 3H), 2.63 (s, 3H); ¹³ CNMR (100 MHz, CDCl ₃ ): δ=161.2, 154.8, 143.4, 137.9, 131.8, 125.2, 124.2 , 114.2, 29.6, 21.7.

The high-resolution mass spectral data of the obtained product are: HRMS (ESI) m/z calcd.for C ₁₀ H ₁₀ N ₃ O ₃ [M+H] ⁺ : 220.0717, found 220.0713.

Example 5

At 25°C, in a 10 mL reaction tube, 7-trifluoromethyl-1-methylquinoxalin-2(1H)-one 1e (0.2 mmol), and iodobenzene diacetate 2a (0.44 mmol) were sequentially added, Ru(bpy) ₃ Cl ₂ ·6H ₂ O (0.002 mmol), PEG-200 (1 mL), mixed uniformly, and then stirred for 7 h under the irradiation of a 12W white LED lamp. After the reaction was detected by TLC, cyclopentyl methyl ether (2ml×3) was added for extraction, and the upper layer extract was taken and concentrated in vacuo to no solvent at 50°C to obtain a crude product, which was then used with petroleum ether in a volume ratio of 2:1. Rinse with ethyl acetate mixed eluent, silica gel column flash column chromatography to obtain 7-trifluoromethyl-1,3-dimethylquinoxalin-2(1H)-one product 3ea in this example, which is White solid 43.6 mg, yield 90%.

The nuclear magnetic spectrum data of the obtained product are: ¹ H NMR (400MHz, CDCl ₃ ): δ=7.91(d, J=8.8Hz, 1H), 7.57(d, J=8.4Hz, 1H), 7.53(s, 1H), 3.73(s, 3H), 2.62(s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ): δ=161.2, 154.9, 134.3, 133.3, 132.0, 131.3, 131.0, 130.2, 125.0, 122.3, 120.2, 120.1, 111.0, 29.2, 21.8; ¹⁹ F NMR (376 MHz, CDCl ₃ ): δ=-62.3.

The high-resolution mass spectrum data of the obtained product are: HRMS (ESI) m/z calcd.for C ₁₁ H ₁₀ F ₃ N ₂ O[M+H] ⁺ : 243.0740, found 243.0744.

Example 6

At 25°C, in a 10 mL reaction tube, 7-trifluoromethyl-1-methylquinoxalin-2(1H)-one 1f (0.2 mmol), and iodobenzene diacetate 2a (0.44 mmol) were sequentially added, Ru(bpy) ₃ Cl ₂ ·6H ₂ O (0.002 mmol), PEG-200 (1 mL), mixed uniformly, and then stirred for 8 h under the irradiation of a 12W white LED lamp. After the reaction was detected by TLC, cyclopentyl methyl ether (2ml×3) was added for extraction, and the upper layer extract was taken and concentrated in vacuo to no solvent at 50°C to obtain a crude product, which was then used with petroleum ether in a volume ratio of 2:1. Rinse with ethyl acetate mixed eluent, silica gel column flash column chromatography to obtain 6-methyl-1,3-dimethylquinoxalin-2(1H)-one product 3fa in this example, which is a white solid 40.4 mg, yield 87%.

The nuclear magnetic spectrum data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ): δ=8.48 (d, J=2.0 Hz, 1H), 8.17 (dd, J ₁ =8.8 Hz, J ₂ =2.0 Hz, 1H), 7.32 (d, J=8.4 Hz, 1H), 3.95 (s, 3H), 3.72 (s, 3H), 2.60 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ): δ=166.1, 159.4, 155.1 ,136.5,132.0,131.3,130.4,125.5,113.6,52.3,29.3,21.6.

The high-resolution mass spectrometry data of the obtained product are: HRMS (ESI) m/z calcd.for C ₁₂ H ₁₃ N ₂ O ₃ [M+H] ⁺ : 233.0921, found 233.0919.

Example 7

At 25°C, in a 10 mL reaction tube, 1,6,7-trimethylquinoxalin-2(1H)-one 1 g (0.2 mmol), iodobenzene diacetate 2a (0.44 mmol), Ru ( bpy) ₃ Cl ₂ ·6H ₂ O (0.002 mmol), PEG-200 (1 mL), mixed well, and then stirred for 8 h under the irradiation of a 12W white LED lamp. After the reaction was detected by TLC, cyclopentyl methyl ether (2ml×3) was added for extraction, and the upper layer extract was taken and concentrated in vacuo to no solvent at 50°C to obtain a crude product, which was then used with petroleum ether in a volume ratio of 2:1. Rinse with ethyl acetate mixed eluent, and perform flash column chromatography on silica gel to obtain the 1,3,6,7-tetramethylquinoxalin-2(1H)-one product 3ga in this example, which is a white solid 33.5 mg, the yield is 83%.

The nuclear magnetic spectrum data of the obtained product are: ¹ H NMR (400MHz, CDCl ₃ ): δ=7.54(s, 1H), 7.04(s, 1H), 3.67(s, 3H), 2.56(s, 3H), 2.40(s , 3H), 2.33(s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ): δ=157.0, 155.3, 139.2, 132.4, 131.2, 131.0, 129.5, 114.2, 28.9, 21.5, 20.5, 19.2.

The high-resolution mass spectrum data of the obtained product is: HRMS (ESI) m/z calcd.for C ₁₂ H ₁₅ N ₂ O[M+H] ⁺ : 203.1179, found 203.1176.

Example 8

In a 10 mL reaction tube at 25°C, 1-benzylquinoxalin-2(1H)-one 1h (0.2 mmol), iodobenzene diacetate 2a (0.44 mmol), Ru(bpy) ₃ Cl ₂ were sequentially added to a 10 mL reaction tube · 6H ₂ O (0.002 mmol), PEG-200 (1 mL), mixed well, and then under the irradiation of a 12W white LED lamp, the reaction was stirred for 6 h. After the reaction was detected by TLC, cyclopentyl methyl ether (2ml×3) was added for extraction, and the upper layer extract was taken and concentrated in vacuo to no solvent at 50°C to obtain a crude product, which was then used with petroleum ether in a volume ratio of 2:1. Rinse with ethyl acetate mixed eluent, silica gel column flash column chromatography to obtain 3-methyl-1-benzylquinoxalin-2(1H)-one product 3ha in this example, which is 43.5mg of white solid, Yield 87%.

The nuclear magnetic spectrum data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ): δ=7.82 (dd, J ₁ =7.6 Hz, J ₂ =1.6 Hz, 1H), 7.42-7.38 (m, 1H), 7.34-7.27 (m, 4H), 7.25-7.23 (m, 3H), 5.50 (s, 2H), 2.66 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ): δ=158.5, 155.3, 135.2, 132.9, 132.6 ,129.6,129.6,128.9,127.7,126.9,123.7,114.4,45.9,21.7.

Example 9

In a 10 mL reaction tube at 25°C, 1-propargylquinoxalin-2(1H)-one 1i (0.2 mmol), iodobenzene diacetate 2a (0.44 mmol), and Ru(bpy) ₃ Cl were sequentially added to a 10 mL reaction tube. ₂ · 6H ₂ O (0.002 mmol), PEG-200 (1 mL), mixed well, and then under the irradiation of a 12W white LED lamp, the reaction was stirred for 7 h. After the reaction was detected by TLC, cyclopentyl methyl ether (2ml×3) was added for extraction, and the upper layer extract was taken and concentrated in vacuo to no solvent at 50°C to obtain a crude product, which was then used with petroleum ether in a volume ratio of 2:1. Rinse with ethyl acetate mixed eluent, silica gel column flash column chromatography to obtain 3-methyl-1-propargylquinoxalin-2(1H)-one product 3ia in this example, as white solid 43.5mg , the yield is 95%.

The nuclear magnetic spectrum data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ): δ=7.82 (dd, J ₁ =8.0 Hz, J ₂ =1.6 Hz, 1H), 7.58-7.54 (m, 1H), 7.46-7.44 (m, 1H), 7.38–7.34 (m, 1H), 5.05 (d, J=2.8Hz, 2H), 2.60 (s, 3H), 2.29 (t, J=2.4Hz, 1H); ¹³ C NMR ( 100MHz, CDCl ₃ ): δ=158.3, 154.2, 132.8, 131.7, 129.7, 129.6, 124.0, 114.1, 76.8, 73.2, 31.5, 21.5.

The high-resolution mass spectral data of the obtained product are: HRMS (ESI) m/z calcd.for C ₁₂ H ₁₁ N ₂ O[M+H] ⁺ : 199.0866, found 199.0862.

Example 10

At 25°C, in a 10 mL reaction tube, sequentially added 2-(2-oxoquinoxalin-1(2H)-yl)ethyl acetate 1j (0.2 mmol), and iodobenzene diacetate 2a (0.44 mmol), Ru(bpy) ₃ Cl ₂ ·6H ₂ O (0.002 mmol), PEG-200 (1 mL), mixed uniformly, and then stirred for 8 h under the irradiation of a 12W white LED lamp. After the reaction was detected by TLC, cyclopentyl methyl ether (2ml×3) was added for extraction, and the upper layer extract was taken and concentrated in vacuo to no solvent at 50°C to obtain a crude product, which was then used with petroleum ether with a volume ratio of 2:1. Rinse with ethyl acetate mixed eluent, silica gel column flash column chromatography to obtain 3-methyl-2-(2-oxoquinoxalin-1(2H)-yl) ethyl acetate product 3ja in this example , as a white solid 39.8 mg, the yield is 81%.

The nuclear magnetic spectrum data of the obtained product are: ¹ H NMR (400 MHz, CDCl ₃ ): δ=7.83 (dd, J ₁ =8.0 Hz, J ₂ =1.6 Hz, 1H), 7.51-7.47 (m, 1H), 7.36-7.32 (m, 1H), 7.06(dd, J ₁ =8.4Hz, J ₂ =0.8Hz, 1H), 5.02(s, 2H), 4.28–4.22(m, 2H), 2.61(s, 3H), 1.27( t, J=7.2 Hz, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ): δ=167.1, 158.2, 154.8, 132.7, 132.4, 129.8, 129.7, 123.9, 113.0, 62.1, 43.5, 21.5, 14.1

The high-resolution mass spectral data of the obtained product are: HRMS (ESI) m/z calcd.for C ₁₃ H ₁₅ N ₂ O ₃ [M+H] ⁺ : 247.1077, found 247.1068.

Example 11

At 25°C, in a 10 mL reaction tube, sequentially add 1-phenylquinoxalin-2(1H)-one 1k (0.2 mmol), iodobenzene diacetate 2a (0.44 mmol), Ru(bpy) ₃ Cl ₂ · 6H ₂ O (0.002 mmol), PEG-200 (1 mL), mixed well, and then under the irradiation of a 12W white LED lamp, the reaction was stirred for 6 h. After the reaction was detected by TLC, cyclopentyl methyl ether (2ml×3) was added for extraction, and the upper layer extract was taken and concentrated in vacuo to no solvent at 50°C to obtain a crude product, which was then used with petroleum ether in a volume ratio of 2:1. Rinse with ethyl acetate mixed eluent, silica gel column flash column chromatography, obtain 3-methyl-1-phenylquinoxalin-2(1H)-one product 3ka in this example, it is white solid 42.5mg, Yield 90%.

The nuclear magnetic spectrum data of the obtained product are: ¹ H NMR (400MHz, CDCl ₃ ): δ=7.86-7.83(m, 1H), 7.63-7.53(m, 3H), 7.33-7.28(m, 4H), 6.67-6.65( m, 1H), 2.64 (s, 3H); ¹³ CNMR (100 MHz, CDCl ₃ ): δ=159.2, 154.9, 135.8, 134.1, 132.5, 130.3, 129.4, 129.2, 129.0, 128.2, 123.8, 115.4, 21.4.

Example 12

At 25°C, in a 10 mL reaction tube, sequentially add 1-allylquinoxalin-2(1H)-one 11 (0.2 mmol), iodobenzene diacetate 2a (0.44 mmol), Ru(bpy) ₃ Cl ₂ · 6H ₂ O (0.002 mmol), PEG-200 (1 mL), mixed well, and then stirred for 8 h under the irradiation of a 12W white LED lamp. After the reaction was detected by TLC, cyclopentyl methyl ether (2ml×3) was added for extraction, and the upper layer extract was taken and concentrated in vacuo to no solvent at 50°C to obtain a crude product, which was then used with petroleum ether in a volume ratio of 2:1. Rinse with ethyl acetate mixed eluent, silica gel column flash column chromatography to obtain 3-methyl-1-allylquinoxalin-2(1H)-one product 3la in this example, which is 36.4 mg of white solid , the yield is 91%.

The nuclear magnetic spectrum data of the obtained product are: ¹ H NMR (400MHz, CDCl ₃ ): δ=7.81(d, J=8.0Hz, 1H), 7.48(t, J=7.6Hz, 1H), 7.34-7.28(m, 2H) ), 5.98–5.88(m, 1H), 5.26(d, J＝12.0Hz, 1H), 5.16(d, J＝16.8Hz, 1H), 4.90(d, J＝4.8Hz, 2H), 2.61(s , 3H); ¹³ CNMR (100 MHz, CDCl ₃ ): δ=158.4, 154.7, 132.8, 132.4, 130.6, 129.5, 129.5, 123.6, 118.0, 114.2, 44.5, 21.5.

The high-resolution mass spectrum data of the obtained product is: HRMS (ESI) m/z calcd.for C ₁₂ H ₁₃ N ₂ O[M+H] ⁺ : 201.1022, found 201.1019.

Claims (4)

1. A preparation method of 3-methylquinoxaline-2 (1H) -ketone compounds is characterized in that: carrying out visible light catalytic reaction on the quinoxalinone compound with the structure of formula 1 and iodobenzene diacetate with the structure of formula 2 under the action of a photocatalyst to obtain a 3-methyl quinoxalinone compound with the structure of formula 3;

wherein,

R₁is hydrogen, alkyl or aralkyl;

R₂and R₃Independently selected from hydrogen, alkyl, alkoxy, nitro, amino, acyl, halogen substituents, hydroxy, cyano or trifluoromethyl;

R₁when selected from alkyl, the alkyl is C₁~C₈Alkyl groups of (a); r₁When selected from aralkyl, the aralkyl is benzyl or phenylethyl;

R₂or R₃When alkyl is selected, the alkyl is C₁~C₈Alkyl groups of (a); r₂Or R₃When alkoxy is selected, alkoxy is C₁~C₈Alkoxy group of (a); r₂Or R₃When acyl is selected, the acyl is formyl, acetyl or propionyl; r₂Or R₃When a halogen substituent is selected, the halogen substituent is fluorine, chlorine, bromine or iodine;

the photocatalyst is Ru (bpy)₃Cl₂At least one of eosin B, water-soluble eosin, alcohol-soluble eosin, rhodamine B and edible pigment red;

the photocatalytic reaction is carried out in DMSO, DMF, CHCl₃、CH₃OH, PEG-200 and PEG-400.

2. The process according to claim 1 for preparing 3-methylquinoxalin-2 (1H) -ones, wherein:

the mol ratio of the quinoxaline-2 (1H) -ketone derivative to iodobenzene diacetate is as follows: 1: 1-1: 20;

the molar ratio of the quinoxaline-2 (1H) -ketone derivative to the photocatalyst is 1: 0.01-1: 0.05.

3. The process for preparing 3-methylquinoxalin-2 (1H) -ones according to claim 1 or 2, characterized in that: the visible light catalytic reaction conditions are as follows: and reacting for 6-12 hours at room temperature under the irradiation of visible light.

4. The process for preparing 3-methylquinoxalin-2 (1H) -ones according to claim 3, characterized in that: the visible light catalytic reaction adopts an LED white light source with the power of 3W-24W, a blue light source with the power of 3W-24W or a green light source with the power of 3W-24W.