Synthesis method of methylated product of nitrogen heterocyclic or oxygen heterocyclic compound

Abstract

The invention discloses a method for synthesizing methylated products of nitrogen heterocyclic and oxygen heterocyclic compounds, which comprises the following synthesis processes: firstly, placing a target heterocyclic compound in a glass reaction container, then adding dimethyl sulfoxide (DMSO) as a methyl donor and a solvent, adopting fluorescein as a photocatalyst, adding 1, 2, 4-trimethyl-1, 3, 4-trimethyl-1, 3, 4-trimethyl-1, 3, 4-trimethyl-1, 3, 4-trimethyl-1, 3, 4-trimethyl-1, 3, 4-trimethyl-1, 3, 4 2, 4-diazabicyclo [2.2. 2] octane (DABCO) is used as an alkaline additive. Under the condition of room temperature, a blue light source with the power being 10 watts and the wavelength being 455 nanometers is used for carrying out illumination stirring reaction. And after the reaction is completed, purifying through a column chromatography separation technology to finally obtain the methyl-substituted nitrogen heterocyclic or oxygen heterocyclic compound. The unique photocatalytic system disclosed by the invention can efficiently realize methylation reaction of nitrogen heterocyclic ring and oxygen heterocyclic ring without depending on a metal catalyst or a strong oxidant, and excellent yield and good functional group compatibility are obtained.

Description

Technical Field

[0001] The invention belongs to the field of organic synthetic chemistry, and in particular relates to a method for synthesizing a methylation product of a nitrogen heterocyclic or oxygen heterocyclic compound. Background Art

[0002] Methylation reaction plays an important role in the pharmaceutical field and pharmaceutical chemical industry. It plays a vital role in enhancing the activity, stability and bioavailability of drug molecules (EJ Barreiro et al, Chem. Rev., 2011, 111, 5215–5246; Q. Zhang, et al, Acc. Chem. Res., 2012, 45, 555–564; J. Chatterjee, et al, Angew. Chem., 2013, 125, 268–283.). Among many methylation reagents, dimethyl sulfoxide (DMSO) has become a new methyl source with its unique advantages such as low cost, easy availability and high reactivity, opening up a new path for methylation reactions (Q. Li, et al, Chem–Eur. J., 2023, 29, e202302542.). Compared with traditional methylation reagents, DMSO is not only cheaper, but also has mild reaction conditions and is easy to operate, which greatly improves the efficiency and controllability of the methylation reaction. Among them, the Fenton methylation reaction, as an important way to use DMSO as a methyl source, has successfully achieved the methylation of a series of heterocyclic compounds (E. Jones-Mensah., et al, Synthesis, 2016, 48, 1421–1436; R. Caporaso., et al, Chem. Commun., 2016, 52, 12486–12489), providing strong technical support for the development of new drugs and the production of pharmaceutical and chemical products. However, the traditional Fenton methylation reaction often requires the use of metal catalysts and strong oxidants, which not only increases the cost and complexity of the reaction, but also may cause environmental pollution. Therefore, the development of a green, efficient, and environmentally friendly DMSO-based methylation reaction method is of great significance for promoting the sustainable development of the pharmaceutical field and the pharmaceutical and chemical industry.

[0003] Quinoxalinone and coumarin heterocyclic compounds are an important class of organic molecular skeletons, widely present in a variety of drug molecules and functional material molecules (S. Vandekerckhove, et al, Bioorg. Med. Chem., 2015, 23, 5098–5119; Y. Pan, et al, New J. Chem., 2023, 47, 21361–21365), such as the quinoxaline with significant anti-tumor activity and the highly sensitive fluorescent probe QNO-ADs material (Anal. Chem. 2022, 94, 7665), both of which are based on their unique heterocyclic structures and show excellent biological activity and physicochemical properties. Therefore, precise modification of such heterocyclic structures to expand their application range and improve performance has always been a hot topic in the field of chemical research.

[0004] In recent years, despite the progress made in the structural modification of quinoxalinone and coumarin heterocyclic compounds, most methods still rely on transition metal catalysis or the use of large amounts of oxidants (G. Yang, et al, Org. Lett., 2022, 24, 9, 1859–1864; V. Vedovato, et al, Org. Lett,. 2024, 26, 3,647–652.), which not only increases the reaction cost, but also may cause environmental pollution problems. Photocatalytic organic synthesis reaction, as an emerging strategy, provides a new idea for the structural modification of heterocyclic compounds with its mild reaction conditions and efficient catalytic performance. However, at present, whether it is metal catalysis or photocatalysis, it is often limited to the structural modification of nitrogen heterocyclic compounds or oxygen heterocyclic compounds. For the simultaneous realization of nitrogen heterocyclic and oxygen heterocyclic reactions, especially the methylation reactions of quinoxalinone and coumarin compounds, there is still a lack of strategies with excellent substrate universality. In view of this, the present invention aims to explore a new photocatalytic strategy to achieve the methylation reaction of quinoxalinone and coumarin heterocyclic compounds, and provide a new green and efficient way for the modification of such important heterocyclic structures. Summary of the invention

[0005] The present invention is dedicated to exploring new approaches for methylation structural modification of quinoxalinone and coumarin heterocyclic compounds. By innovatively using dimethyl sulfoxide as a methyl source, a heterocyclic structural modification strategy with strong substrate compatibility and wide applicability is developed, aiming to provide an efficient and green new method for the functionalization of such important compounds.

[0006] The idea of ​​the present invention is to use quinoxalinone and coumarin heterocyclic compounds as raw materials, dimethyl sulfoxide as methyl source and solvent, 1,4-diazabicyclo[2.2.2]octane (DABCO) as base, and stir the reaction at room temperature under 10 watt 455 nm wavelength blue light irradiation to achieve efficient construction of methylation products of nitrogen heterocyclic or oxygen heterocyclic compounds. The reaction is achieved through a photocatalytic strategy, has excellent substrate universality, can simultaneously achieve methylation reactions of oxygen heterocyclic and nitrogen heterocyclic, and the reaction conditions are mild and avoid the use of metal catalysts and strong oxidants.

[0007] The purpose of the present invention is achieved through the following technical solutions.

[0008] A method for synthesizing a methylated product of a nitrogen heterocyclic or oxygen heterocyclic compound comprises the following steps:

[0009] First, a nitrogen heterocyclic or oxygen heterocyclic compound is placed in a glass reaction container, and then dimethyl sulfoxide (DMSO), a photocatalyst and a base are added in proportion. Under room temperature, a blue light source with a power of 10 watts and a wavelength of 455 nanometers is used for illumination and stirring reaction. After the reaction is completed, it is immediately filtered to separate solid impurities. Subsequently, the filtrate is extracted multiple times with ethyl acetate to ensure that the target product is fully transferred to the organic phase, and these organic phases containing the target product are combined. Then, the organic solvent is removed by vacuum rotary evaporation to obtain a crude product. Finally, the crude product is deeply purified using column chromatography separation technology to accurately obtain the methylation product of the nitrogen heterocyclic or oxygen heterocyclic compound;

[0010] Further, the chemical reaction equation for preparing the methylation product of nitrogen heterocyclic or oxygen heterocyclic compound is as follows:

[0011]

[0012] In the formula, R 1 is selected from the group consisting of methyl, ethyl, allyl, propargyl, and benzyl; R 2 is selected from one of hydrogen, methyl and chlorine; R 3 is selected from one of hydrogen, methyl, trifluoromethyl and chlorine; R 4 is selected from one of hydrogen, methoxy and bromine; R 5 One selected from hydrogen, methyl and nitro.

[0013] Furthermore, the photocatalyst is one of eosin Y, eosin Y disodium salt, rhodamine B, rhodamine 6G, rose Bengal, 4CzIPN, 9,10-phenanthrenequinone and fluorescein, preferably fluorescein.

[0014] Furthermore, the base is one of quinuclidine, Na2CO3, NaHCO3, K2CO3, morpholine, DBU, DABSO, TMEDA and DABCO, preferably DABCO.

[0015] Furthermore, the molar ratio of the nitrogen heterocyclic or oxygen heterocyclic compound to DMSO is 1:10-50, preferably 1:26.

[0016] Furthermore, the molar ratio of the nitrogen heterocyclic or oxygen heterocyclic compound to the photocatalyst is 1:0.01-1, preferably 1:0.08.

[0017] Furthermore, the molar ratio of the nitrogen heterocyclic or oxygen heterocyclic compound to the base is 1:0.1-3, preferably 1:1.5.

[0018] Furthermore, the reaction time of the preparation method is 3 to 30 hours, preferably 22 hours.

[0019] Furthermore, the methylation product of the nitrogen heterocyclic or oxygen heterocyclic compound is purified by column chromatography, and a mixed solvent of petroleum ether and ethyl acetate is selected as the eluent, wherein the volume ratio of petroleum ether to ethyl acetate is set between 1 and 100:1, and the most preferred eluent ratio is petroleum ether: ethyl acetate = 4:1.

[0020] The principle of the present invention is:

[0021] First, the photocatalyst forms an active catalyst under the action of DABCO, and catalyzes heterocyclic compounds to form aromatic free radical cations, and then generates oxygen heterocyclic or nitrogen heterocyclic free radicals under the action of superoxide free radical anions; at the same time, hydroxyl free radicals are generated under the joint action of photocatalyst, oxygen and water, which promote dimethyl sulfoxide to release methyl cations and by-product methanesulfonic acid; finally, methyl free radicals capture oxygen heterocyclic or nitrogen heterocyclic free radicals to generate the final target product.

[0022] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0023] (1) The present invention realizes a methylation reaction based on DMSO and efficiently constructs a series of methylation products of nitrogen heterocyclic or oxygen heterocyclic compounds. The reaction has excellent substrate universality, and has the characteristics of mild reaction conditions, simple operation and good functional group tolerance.

[0024] (2) The present invention uses oxygen in the air as an oxidant, which significantly improves the economy and environmental friendliness of the reaction compared to the prior art, while avoiding the use of metal catalysts. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 , Figure 2 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 1;

[0026] Figure 3 , Figure 4 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 2;

[0027] Figure 5 , Figure 6 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 3;

[0028] Figure 7 , Figure 8 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 4; DETAILED DESCRIPTION

[0029] The present invention is further described below by means of specific examples, but the protection scope and implementation modes of the present invention are not limited thereto.

[0030] Example 1

[0031] In a transparent glass test tube, accurately weighed 1-methylquinoxaline-2(H)-one (0.1 mmol), dimethyl sulfoxide (DMSO, 26 mmol), fluorescein (0.08 mmol) and 1,4-diazabicyclo[2.2.2]octane (DABCO, 0.15 mmol) were added in sequence, and a stirring bar was added. Subsequently, the mixture was reacted for 22 hours by magnetic stirring under 10 watt power and 455 nm wavelength blue light irradiation. After the reaction was completed, it was immediately filtered. Then, the filtrate was extracted with ethyl acetate several times, and all organic phases containing the target product were combined. The organic solvent was removed by rotary evaporation under reduced pressure to obtain a preliminary product. Finally, the target compound 1,3-dimethylquinoxaline-2(H)-one was obtained by purification by column chromatography with a yield of 75%.

[0032] The hydrogen and carbon spectra of the obtained target product are as follows Figure 1 and Figure 2 The structural characterization data are shown below:

[0033] 1 H NMR (500 MHz, Chloroform-d) δ 7.80 (d, J = 8.0 Hz, 1H), 7.52 (t, J= 7.9 Hz, 1H), 7.33 (t, J = 7.6 Hz, 1H), 7.29 (d, J = 8.4 Hz, 1H), 3.70 (s,3H), 2.59 (s,3H). 13C NMR (126 MHz, Chloroform-d) δ 158.37, 155.19, 133.24,132.60, 129.57, 129.40, 123.59, 113.58, 29.03, 21.55. HRMS calcd for C 10 H 10 N2OH + [M+H] + : 175.0866; found 175.0867.

[0034] The structure of the target compound is inferred from the above characterization data as follows:

[0035]

[0036] Example 2

[0037] In a transparent glass test tube, accurately weighed 1-ethylquinoxaline-2(H)-one (0.1 mmol), dimethyl sulfoxide (DMSO, 26 mmol), fluorescein (0.08 mmol) and 1,4-diazabicyclo[2.2.2]octane (DABCO, 0.15 mmol) were added in sequence, and a stirring bar was added. Subsequently, the mixture was reacted for 22 hours under 10 watt power and 455 nm wavelength blue light irradiation by magnetic stirring. After the reaction was completed, it was immediately filtered. Then, the filtrate was extracted with ethyl acetate several times, and all organic phases containing the target product were combined. The organic solvent was removed by rotary evaporation under reduced pressure to obtain a preliminary product. Finally, the target compound 3-methyl-1-ethylquinoxaline-2(H)-one was obtained by purification by column chromatography with a yield of 80%.

[0038] The hydrogen and carbon spectra of the obtained target product are as follows Figure 3 and Figure 4 The structural characterization data are shown below:

[0039] 1 H NMR (500 MHz, Chloroform-d) δ 7.82 (d, J = 7.9 Hz, 1H), 7.51 (t, J= 7.8 Hz, 1H), 7.32 (dd, J = 8.5, 5.4 Hz, 2H), 4.31 (q, J = 7.2 Hz, 2H), 2.59(s, 3H), 1.37 (t, J = 7.2 Hz, 3H). 13HRMS calcd for C 11 H 12 N2OH + [M+H] + : 189.1022; found 189.1023.

[0040] The structure of the target compound is inferred from the above characterization data as follows:

[0041]

[0042] Example 3

[0043] In a transparent glass test tube, accurately weighed 1-allylquinoxaline-2(H)-one (0.1 mmol), dimethyl sulfoxide (DMSO, 26 mmol), fluorescein (0.08 mmol) and 1,4-diazabicyclo[2.2.2]octane (DABCO, 0.15 mmol) were added in sequence, and a stirring bar was added. Subsequently, the mixture was reacted for 22 hours by magnetic stirring under 10 watt power and 455 nm wavelength blue light irradiation. After the reaction was completed, it was immediately filtered. Then, the filtrate was extracted with ethyl acetate several times, and all organic phases containing the target product were combined. The organic solvent was removed by rotary evaporation under reduced pressure to obtain a preliminary product. Finally, the target compound 3-methyl-1-allylquinoxaline-2(H)-one was obtained by purification by column chromatography with a yield of 66%.

[0044] The hydrogen and carbon spectra of the obtained target product are as follows Figure 5 and Figure 6 The structural characterization data are shown below:

[0045] 1H NMR (500 MHz, Chloroform-d) δ 7.82 (d, J = 7.9 Hz, 1H), 7.49 (t, J= 7.8 Hz, 1H), 7.33 (t, J = 7.6 Hz, 1H), 7.28 (d, J = 9.3 Hz, 1H), 5.94 (ddd,J = 22.4, 10.3, 5.1 Hz, 1H), 5.27 (d, J = 10.5 Hz, 1H), 5.17 (d, J = 17.2 Hz, 1H), 4.91 (d, J = 4.7 Hz, 2H), 2.62 (s, 3H). 13 HRMS calcd for C 12 H 12 N2OH + [M+H] + : 201.1022; found201.1022.

[0046] The structure of the target compound is inferred from the above characterization data as follows:

[0047]

[0048] Example 4

[0049] In a transparent glass test tube, accurately weighed 1-propargylquinoxaline-2(H)-one (0.1 mmol), dimethyl sulfoxide (DMSO, 26 mmol), fluorescein (0.08 mmol) and 1,4-diazabicyclo[2.2.2]octane (DABCO, 0.15 mmol) were added in sequence, and a stirring bar was added. Subsequently, the mixture was reacted for 22 hours under 10 watt power and 455 nm wavelength blue light irradiation by magnetic stirring. After the reaction was completed, it was immediately filtered. Then, the filtrate was extracted with ethyl acetate several times, and all organic phases containing the target product were combined. The organic solvent was removed by rotary evaporation under reduced pressure to obtain a preliminary product. Finally, the target compound 3-methyl-1-propargylquinoxaline-2(H)-one was obtained by purification by column chromatography with a yield of 58%.

[0050] The hydrogen and carbon spectra of the obtained target product are as follows Figure 7 and Figure 8The structural characterization data are shown below:

[0051] 1 H NMR (500 MHz, Chloroform-d) δ 7.82 (d, J = 8.0 Hz, 1H), 7.55 (t, J= 7.8 Hz, 1H), 7.45 (d, J = 8.3 Hz, 1H), 7.38-7.34 (m, 1H), 5.05 (s, 2H), 2.60 (s, 3H), 2.28 (s, 1H). 13 HRMS calcd for C 12 H 10 N2OH + [M+H] + : 199.0866; found 199.0865.

[0052] The structure of the target compound is inferred from the above characterization data as follows:

[0053]

[0054] Example 5

[0055] In a transparent glass test tube, accurately weighed 1-benzylquinoxaline-2(H)-one (0.1 mmol), dimethyl sulfoxide (DMSO, 26 mmol), fluorescein (0.08 mmol) and 1,4-diazabicyclo[2.2.2]octane (DABCO, 0.15 mmol) were added in sequence, and a stirring bar was added. Subsequently, the mixture was reacted for 22 hours under 10 watt power and 455 nm wavelength blue light irradiation by magnetic stirring. After the reaction was completed, it was immediately filtered. Then, the filtrate was extracted with ethyl acetate several times, and all organic phases containing the target product were combined. The organic solvent was removed by rotary evaporation under reduced pressure to obtain a preliminary product. Finally, the target compound 3-methyl-1-benzylquinoxaline-2(H)-one was obtained by purification by column chromatography with a yield of 75%.

[0056] The structural characterization data of the obtained target product are shown below:

[0057] 1H NMR (500 MHz, Chloroform-d) δ 7.84 (d, J = 8.0 Hz, 1H), 7.45-7.40(m, 1H), 7.36-7.32 (m, 3H), 7.31-7.27 (m, 3H), 5.53 (s, 2H), 2.69 (s, 3H). 13 CNMR (126 MHz, Chloroform-d) δ 158.52, 155.29, 135.25, 132.90, 132.61, 129.57,129.54, 128.92, 127.68, 126.86, 123.65, 114.42, 45.91, 21.65. HRMS calcd forC 16 H 14 N2OH + [M+H] + : 251.1179; found 251.1175.

[0058] The structure of the target compound is inferred from the above characterization data as follows:

[0059]

[0060] Example 6

[0061] In a transparent glass test tube, accurately weighed 6,7-dimethyl-1-ethylquinoxalin-2(H)-one (0.1 mmol), dimethyl sulfoxide (DMSO, 26 mmol), fluorescein (0.08 mmol) and 1,4-diazabicyclo[2.2.2]octane (DABCO, 0.15 mmol) were added in sequence, and a stirring bar was added. Subsequently, the mixture was reacted for 22 hours under 10 watts of blue light with a wavelength of 455 nanometers by magnetic stirring. After the reaction was completed, it was immediately filtered. Then, the filtrate was extracted with ethyl acetate several times, and all organic phases containing the target product were combined. The organic solvent was removed by rotary evaporation under reduced pressure to obtain a preliminary product. Finally, the target compound 4,6,7-trimethyl-1-ethylquinoxalin-2(H)-one was obtained by purification by column chromatography with a yield of 79%.

[0062] The structural characterization data of the obtained target product are shown below:

[0063] 1H NMR (400 MHz, Chloroform-d) δ 7.55 (s, 1H), 7.06 (s, 1H), 4.28 (q,J = 7.2 Hz, 2H), 2.56 (s, 3H), 2.40 (s, 3H), 2.33 (s, 3H), 1.36 (t, J = 7.2Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 157.08, 154.73, 139.13, 132.21,131.41, 130.12, 129.78, 113.92, 37.07, 21.37, 20.51, 19.14, 12.42. HRMS calcdfor C 13 H 16 N2O H + [M+H] + : 217.1335; found 217.1335.

[0064] The structure of the target compound is inferred from the above characterization data as follows:

[0065]

[0066] Example 7

[0067] In a transparent glass test tube, accurately weighed 1-ethyl-7-trifluoromethylquinoxalin-2(H)-one (0.1 mmol), dimethyl sulfoxide (DMSO, 26 mmol), fluorescein (0.08 mmol) and 1,4-diazabicyclo[2.2.2]octane (DABCO, 0.15 mmol) were added in sequence, and a stirring bar was added. Subsequently, the mixture was reacted for 22 hours under 10 watt power and 455 nm wavelength blue light irradiation by magnetic stirring. After the reaction was completed, it was immediately filtered. Then, the filtrate was extracted with ethyl acetate several times, and all organic phases containing the target product were combined. The organic solvent was removed by rotary evaporation under reduced pressure to obtain a preliminary product. Finally, the target compound 3-methyl-1-ethyl-7-trifluoromethylquinoxalin-2(H)-one was obtained by purification by column chromatography with a yield of 80%.

[0068] The structural characterization data of the obtained target product are shown below:

[0069] 1H NMR (400 MHz, Chloroform-d) δ 8.09 (d, J = 1.4 Hz, 1H), 7.73 (dd,J = 8.8, 2.1 Hz, 1H), 7.40 (d, J = 8.8 Hz, 1H), 4.33 (q, J = 7.2 Hz, 2H),2.61 (s, 3H), 1.39 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ160.21, 154.52, 134.55, 132.35, 127.24, 127.24, 125.87, 114.04, 37.58, 21.53,12.35. 19 F NMR (376 MHz, Chloroform-d) δ -62.01. HRMS calcd for C 12 H 11 F3N2OH + [M+H] + : 257.0896; found 257.0891.

[0070] The structure of the target compound is inferred from the above characterization data as follows:

[0071]

[0072] Example 8

[0073] In a transparent glass test tube, accurately weighed 1-ethyl-6,7-dichloroquinoxaline-2(H)-one (0.1mmol), dimethyl sulfoxide (DMSO, 26mmol), fluorescein (0.08mmol) and 1,4-diazabicyclo[2.2.2]octane (DABCO, 0.15mmol) were added in sequence, and a stirring bar was added. Subsequently, the mixture was reacted for 22 hours by magnetic stirring under 10W power and 455nm wavelength blue light irradiation. After the reaction was completed, it was immediately filtered. Then, the filtrate was extracted with ethyl acetate several times, and all organic phases containing the target product were combined. The organic solvent was removed by rotary evaporation under reduced pressure to obtain a preliminary product. Finally, the target compound 3-methyl-1-ethyl-6,7-dichloroquinoxaline-2(H)-one was obtained by purification by column chromatography with a yield of 77%.

[0074] The structural characterization data of the obtained target product are shown below:

[0075] 1H NMR (400 MHz, Chloroform-d) δ 7.88 (s, 1H), 7.38 (s, 1H), 4.24 (q,J = 7.2 Hz, 2H), 2.57 (s, 3H), 1.37 (t, J = 7.2 Hz, 3H). 13 HRMS calcd for C 11 H 10 Cl2N2OH + [M+H] + : 257.0243; found 257.0241.

[0076] The structure of the target compound is inferred from the above characterization data as follows:

[0077]

[0078] Example 9

[0079] In a transparent glass test tube, accurately weighed coumarin (0.1 mmol), dimethyl sulfoxide (DMSO, 26 mmol), fluorescein (0.08 mmol) and 1,4-diazabicyclo[2.2.2]octane (DABCO, 0.15 mmol) were added in sequence, and a stirring bar was added. Subsequently, the mixture was reacted for 48 hours by magnetic stirring under 10 watts of blue light with a wavelength of 455 nanometers. After the reaction was completed, it was immediately filtered. Then, the filtrate was extracted with ethyl acetate several times, and all organic phases containing the target product were combined. The organic solvent was removed by rotary evaporation under reduced pressure to obtain a preliminary product. Finally, the target compound 3-methylcoumarin was purified by column chromatography with a yield of 57%.

[0080] The structural characterization data of the obtained target product are shown below:

[0081] 1 H NMR (400 MHz, Chloroform-d) δ 7.55 (s, 1H), 7.52-7.46 (m, 1H), 7.45 (d, J = 7.8 Hz, 1H), 7.33 (d, J = 8.2 Hz, 1H), 7.31-7.27 (m, 1H), 2.25(s, 3H). 13C NMR (101 MHz, Chloroform-d) δ 162.14, 153.19, 139.15, 130.38,126.88, 125.77, 124.20, 119.53, 116.37, 17.10. HRMS calcd for C 10 H8O2H + [M+H] + :161.0597; found 161.0596.

[0082] The structure of the target compound is inferred from the above characterization data as follows:

[0083]

[0084] Example 10

[0085] In a transparent glass test tube, accurately weighed 6-methylcoumarin (0.1 mmol), dimethyl sulfoxide (DMSO, 26 mmol), fluorescein (0.08 mmol) and 1,4-diazabicyclo[2.2.2]octane (DABCO, 0.15 mmol) were added in sequence, and a stirrer was added. Subsequently, the mixture was reacted for 48 hours by magnetic stirring under 10 watts of blue light with a wavelength of 455 nanometers. After the reaction was completed, it was immediately filtered. Then, the filtrate was extracted with ethyl acetate several times, and all organic phases containing the target product were combined. The organic solvent was removed by rotary evaporation under reduced pressure to obtain a preliminary product. Finally, the target compound 3,6-dimethylcoumarin was obtained by purification by column chromatography with a yield of 61%.

[0086] The structural characterization data of the obtained target product are shown below:

[0087] 1 H NMR (500 MHz, Chloroform-d) δ 7.46 (s, 1H), 7.25 (d, J = 8.4 Hz,1H), 7.19 (dd, J = 5.3, 3.2 Hz, 2H), 2.39 (s, 3H), 2.20 (s, 3H). 13 HRMS calcd for C 11 H 10 O2H +[M+H] + : 175.0754; found175.0758.

[0088] The structure of the target compound is inferred from the above characterization data as follows:

[0089]

[0090] Embodiment 11

[0091] In a transparent glass test tube, accurately weighed 7-methoxycoumarin (0.1 mmol), dimethyl sulfoxide (DMSO, 26 mmol), fluorescein (0.08 mmol) and 1,4-diazabicyclo[2.2.2]octane (DABCO, 0.15 mmol) were added in sequence, and a stirring bar was added. Subsequently, the mixture was reacted for 48 hours by magnetic stirring under 10 watt power and 455 nm wavelength blue light irradiation. After the reaction was completed, it was immediately filtered. Then, the filtrate was extracted with ethyl acetate several times, and all organic phases containing the target product were combined. The organic solvent was removed by rotary evaporation under reduced pressure to obtain a preliminary product. Finally, the target compound 3-methyl-7-methoxycoumarin was obtained by purification by column chromatography with a yield of 59%.

[0092] The structural characterization data of the obtained target product are shown below:

[0093] 1 H NMR (500 MHz, Chloroform-d) δ 7.46 (s, 1H), 7.31 (d, J = 8.4 Hz,1H), 6.84-6.80 (m, 2H), 3.86 (s, 3H), 2.17 (s, 3H). 13 HRMS calcd for C 11 H 10 3H + [M+H] + : 191.0703; found191.0703.

[0094] The structure of the target compound is inferred from the above characterization data as follows:

[0095]

[0096] Example 12

[0097] In a transparent glass test tube, accurately weighed 7-bromocoumarin (0.1 mmol), dimethyl sulfoxide (DMSO, 26 mmol), fluorescein (0.08 mmol) and 1,4-diazabicyclo[2.2.2]octane (DABCO, 0.15 mmol) were added in sequence, and a stirring bar was added. Subsequently, the mixture was reacted for 48 hours by magnetic stirring under 10 watt power and 455 nm wavelength blue light irradiation. After the reaction was completed, it was immediately filtered. Then, the filtrate was extracted with ethyl acetate several times, and all organic phases containing the target product were combined. The organic solvent was removed by rotary evaporation under reduced pressure to obtain a preliminary product. Finally, the target compound 3-methyl-7-bromocoumarin was obtained by purification by column chromatography with a yield of 53%.

[0098] The structural characterization data of the obtained target product are shown below:

[0099] 1 H NMR (500 MHz, Chloroform-d) δ 7.57 (d, J = 7.7 Hz, 2H), 7.46 (s,1H), 7.23 (d, J = 10.0 Hz, 1H), 2.25 (s, 3H). 13 HRMS calcd for C 10 H7BrO2H + [M+H] + : 238.9702; found 238.9700.

[0100] The structure of the target compound is inferred from the above characterization data as follows:

[0101]

[0102] Embodiment 13

[0103] In a transparent glass test tube, accurately weighed 6-nitrocoumarin (0.1 mmol), dimethyl sulfoxide (DMSO, 26 mmol), fluorescein (0.08 mmol) and 1,4-diazabicyclo[2.2.2]octane (DABCO, 0.15 mmol) were added in sequence, and a stirring bar was added. Subsequently, the mixture was reacted for 48 hours by magnetic stirring under 10 watt power and 455 nm wavelength blue light irradiation. After the reaction was completed, it was immediately filtered. Then, the filtrate was extracted with ethyl acetate several times, and all organic phases containing the target product were combined. The organic solvent was removed by rotary evaporation under reduced pressure to obtain a preliminary product. Finally, the target compound 3-methyl-6-nitrocoumarin was obtained by purification by column chromatography with a yield of 57%.

[0104] The structural characterization data of the obtained target product are shown below:

[0105] 1 H NMR (500 MHz, Chloroform-d) δ 8.36 (s, 1H), 8.34 (d, J = 11.6 Hz,1H), 7.60 (s, 1H), 7.44 (d, J = 9.0 Hz, 1H), 2.28 (s, 3H). 13 HRMS calcd for C 10 H7NO4H + [M+H] + : 206.0448; found 206.0438.

[0106] The structure of the target compound is inferred from the above characterization data as follows:

[0107]

[0108] The above-mentioned implementation modes are partial embodiments of the method of the present invention, but they do not limit the specific implementation modes of the present invention. Any other substitutions, basic skeleton changes, and condition simplifications made without departing from the spirit and principle of the present invention should be classified as equivalent replacement methods and are included in the protection scope of the present invention.

Claims

1. A method for synthesizing a methylated product of a nitrogen heterocyclic or oxygen heterocyclic compound, characterized in that: The following steps are included: First, a nitrogen heterocyclic compound or an oxygen heterocyclic compound is placed in a glass reaction container, and then dimethyl sulfoxide (DMSO), a photocatalyst and a base are added in proportion; a blue light source with a power of 10 watts and a wavelength of 455 nanometers is used for light irradiation and stirring reaction at room temperature; after the reaction is completed, it is immediately filtered to separate solid impurities; then, the filtrate is extracted multiple times with ethyl acetate to ensure that the target product is fully transferred to the organic phase, and these organic phases containing the target product are combined; then, the organic solvent is removed by reduced pressure rotary evaporation to obtain a crude product; finally, the crude product is deeply purified by column chromatography separation technology to accurately obtain the methylation product of the nitrogen heterocyclic compound and the oxygen heterocyclic compound; The above reaction is shown in the following formula: ； In the formula, R 1 is selected from the group consisting of methyl, ethyl, allyl, propargyl, and benzyl; R 2 is selected from one of hydrogen, methyl and chlorine; R 3 is selected from one of hydrogen, methyl, trifluoromethyl and chlorine; R 4 is selected from one of hydrogen, methoxy and bromine; R 5 Selected from one of hydrogen, methyl and nitro; the photocatalyst is selected from one of eosin Y, eosin Y disodium salt, rhodamine B, rhodamine 6G, Bengal rose red, 4CzIPN, 9,10-phenanthrenequinone and fluorescein; the base is selected from one of quinuclidine, Na2CO3, NaHCO3, K2CO3, morpholine, DBU, DABSO, TMEDA and DABCO.

2. The preparation method according to claim 1, characterized in that: The molar ratio of the nitrogen heterocyclic or oxygen heterocyclic compound to dimethyl sulfoxide is 1:10-50.

3. The preparation method according to claim 1, characterized in that: The molar ratio of the nitrogen heterocyclic or oxygen heterocyclic compound to the photocatalyst is 1:0.01-1.

4. The preparation method according to claim 1, characterized in that: The molar ratio of the nitrogen heterocyclic or oxygen heterocyclic compound to the base is 1:0.1-3.

5. The preparation method according to claim 1, characterized in that: The reaction time of the preparation method is 3 to 30 hours.

6. The preparation method according to claim 1, characterized in that: The methylation product of the nitrogen heterocyclic or oxygen heterocyclic compound is purified by column chromatography, and a mixed solvent of petroleum ether and ethyl acetate is selected as an eluent, and the volume ratio thereof is petroleum ether:ethyl acetate = 1-100:1.

Images