Method for synthesizing quinoxaline compound through C (sp3)-H amination reaction catalyzed by I2 under visible light condition

Abstract

The invention discloses a method for synthesizing quinoxaline by promoting I2 to catalyze C (sp3)-H amination reaction through visible light. The reaction synthesizes the target product in a single quartz tube through a plurality of basic reactions (iodination, Kornblum oxidation, condensation, etc.). The synthetic process of the method comprises the following steps: in a glass reaction container, adding a photocatalyst, I2 and acetophenone in proportion, carrying out illumination reaction for 1.5 hours at 120 DEG C in a DMSO solvent, then adding o-phenylenediamine, continuously reacting for 3.5 hours, and carrying out column chromatography separation and purification on a crude product to obtain the quinoxaline derivative. According to the invention, the problem of iodine elementary substance catalytic circulation is solved by utilizing a visible light catalytic synthesis means to synthesize quinoxaline and drug molecules 6, 7-dimethyl-2-phenylquinoxaline (3e) and 2-phenylbenzo quinoxaline (3f). Meanwhile, the method avoids the use of oxidants, toxic reagents and expensive raw materials, and is simple and convenient to operate, mild in condition and excellent in separation yield.

Description

Technical Field

[0001] The invention belongs to the field of organic synthetic chemistry, and specifically relates to a method for synthesizing quinoxaline. Background Art

[0002] Quinoxaline has a wide range of biological activities and exists in natural products and drug molecules, such as PET imaging agent of b-amyloid plaques, Chloroquinoxaline sulfonamide Antitumor activity and Brimonidine Antihypertensive. Quinoxaline can also be used as a PET imaging agent (ACS Med. Chem. Lett. 4 (2013) 596-600), antitumor agent and antihypertensive agent (RSC Adv. 11 (2021) 37325–37353). Therefore, organic chemists have conducted extensive research on the synthesis of quinoxaline skeletons. It has been reported that the reaction of o-phenylenediamine with 1,2-dicarbonyl compounds is an efficient method for synthesizing quinoxaline compounds (Res. Chem. Intermed. 41 (2015) 10085-10096, J. Chem. Sci. 129 (2017) 141–148, Synth. Commun. 51 (2021) 1121-1131). With the development of organic synthesis, various reagents such as α-haloketones (Tetrahedron Lett. 56 (2015) 1266-1271, Res. Chem. Intermed. 43 (2017) 4549-4559), α-hydroxyketones (Tetrahedron. 71 (2015) 1831-1837, J. Org. Chem. 86 (2020) 947-958), epoxides (Tetrahedron Lett. 43 (2002) 3971-3973), and alkynes (Tetrahedron. 73 (2017) 1374-1379, J. Org. Chem. 83 (2018) 9422-9429) have been used to react with o-phenylenediamine to construct quinoxaline compounds. In addition, as a precursor of α-haloketone, acetophenone has been identified as the most suitable raw material and exhibits good stability (Adv. Synth. Catal. 366 (2024) 2557–2564). Initially, excess I2 (2 eq.) was used to activate acetophenone and convert it into α-iodoacetophenone, which was subsequently reacted with o-phenylenediamine to produce quinoxaline (Chem. Commun. 50 (2014) 13517–13520). Various strategies have been designed to eliminate the use of excess iodine. Nguyen and co-workers described a sulfur-catalyzed oxidative condensation process involving acetophenone and o-phenylenediamine to prepare quinoxaline using oxalic acid (Adv. Synth. Catal. 364 (2022) 2748–2752).In addition, Liu's group designed an electrochemical oxidative dehydrogenation cyclization method for synthesizing quinoxaline from ketones and phenylenediamine (Synlett.35(2024)A–F). This technique uses electrochemical iodine anions (I. - ) is oxidized to elemental iodine (I2), and then activated acetophenone is converted into α-iodoacetophenone. Although many methods have been reported to prepare quinoxaline compounds, there is still a need to develop an efficient and direct method to synthesize this type of heterocyclic compounds. Summary of the invention

[0003] The purpose of the present invention is to solve the catalytic cycle problem of iodine catalyst in the current synthesis of quinoxaline reaction, and to use a method for synthesizing 2-phenylquinoxaline compounds by iodine catalysis under visible light conditions, wherein acetophenone undergoes a halogenation reaction with I2, and then is further converted into benzoyl formaldehyde through Kornblum oxidation. Then, it undergoes condensation cyclization with o-phenylenediamine, and finally is oxidized to obtain the target product 2-phenylquinoxaline.

[0004] The idea of ​​the present invention is to use o-phenylenediamine and acetophenone as raw materials, add I2 element, use p-Cl-3CzEPAIPN as photocatalyst, DMSO as solvent, and efficiently synthesize 2-phenylquinoxaline compounds under blue light irradiation in an air atmosphere. The p-Cl-3CzEPAIPN photocatalyst used in the present invention can easily generate excited p-Cl-3CzEPAIPN under light conditions. * , iodine is generated by halogenation reaction - The ion is excited to p-Cl-3CzEPAIPN * Oxidation generates I2 element, successfully realizing the recycling of iodine. In addition, the reaction is simple to operate, mild in conditions, and has excellent separation yield, and the substrate has a wide range of applicability.

[0005] The purpose of the present invention is achieved through the following technical solutions.

[0006] A visible light-induced I2-catalyzed C(sp 3 A method for synthesizing quinoxaline by amination reaction of )-H, characterized in that it comprises the following steps:

[0007] In a glass reaction container, acetophenone, photocatalyst and I2 were added in proportion, 3 mL of DMSO was added under air atmosphere, and o-phenylenediamine was added under blue light irradiation and magnetic stirring at 120°C for 1.5 hours to continue the reaction for 3.5 hours. After the reaction was completed, a saturated sodium chloride solution (3 mL) was added, and the reaction mixture was extracted with ethyl acetate (3×3 mL). The organic layer was collected and dried over anhydrous sodium sulfate, and the organic phase was evaporated under reduced pressure to obtain a crude product, and finally the 2-phenylquinoxaline derivative was separated and purified by column chromatography;

[0008] Further, the chemical reaction equation for photocatalytic synthesis of 2-phenylquinoxaline is shown below:

[0009]

[0010] In the formula, R 1 One or more selected from hydrogen, 4,5-dichloro, 4,5-dibromo, 4,5-dimethyl, phenyl, 3,5-dimethyl, 4-chloro, 4-bromo, 3,4-dichloro, 3,4-dimethyl and 3,5-dimethyl;

[0011] Furthermore, the molar ratio of the photocatalyst to the o-phenylenediamine compound is 1:100.

[0012] Furthermore, the organic solvent is one or more of DMSO and DMF, and DMSO is preferably used as the solvent.

[0013] Further, the visible light promotes I2 to catalyze C(sp 3 The reaction time of the method for synthesizing 2-phenylquinoxaline by )-H amination reaction is 4 to 5 hours, and the preferred reaction time is 5 hours.

[0014] Furthermore, the photocatalyst is one or more of 4CzIPN, 4-DPAIPN, 3CzEPAIPN, p-Cl-3CzEPAIPN, p-Me-3CzMPAIPN, o-Me-3CzMPAIPN, and 3CzMPAIPN, preferably p-Cl-3CzEPAIPN.

[0015] Furthermore, the target product 2-phenylquinoxaline derivative is purified by column chromatography, and the eluent can be a mixed solvent of petroleum ether and ethyl acetate, the volume ratio of petroleum ether:ethyl acetate is between 5 and 15:1, and the preferred developing solvent is petroleum ether:ethyl acetate = 10:1.

[0016] The principle of the present invention is: acetophenone undergoes a halogenation reaction with I2 to obtain an intermediate product α-iodoacetophenone, which is further converted into phenylglyoxal by Kornblum oxidation. Then, it undergoes condensation cyclization with o-phenylenediamine to generate an intermediate. Finally, the intermediate is oxidized to obtain the target product 2-phenylquinoxaline. Under light conditions, the photocatalyst p-Cl-3CzEPAIPN easily generates an excited state of p-Cl-3CzEPAIPN * , iodine is generated by halogenation reaction - The ion is excited to p-Cl-3CzEPAIPN * Oxidation generates I2 element, successfully realizing the recycling of iodine. *After a series of redox reactions, p-Cl-3CzEPAIPN is generated. －· After the radical anion is generated, it is oxidized to the ground state p-Cl-3CzEPAIPN by oxygen for the next catalytic cycle.

[0017] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0018] (1) The photocatalyst p-Cl-3CzEPAIPN used in the present invention is easy to generate excited state p-Cl-3CzEPAIPN * , p-Cl-3CzEPAIPN * I - The ions are oxidized to generate I2 elemental substance, thus successfully realizing the recycling of iodine.

[0019] (2) The present invention realizes the catalytic activity of I2 to C(sp 3 )-H amination reaction to synthesize 2-phenylquinoxaline compounds. This reaction does not require the addition of excess oxidant, has mild conditions, is easy to operate, has excellent separation yield, and has a wide range of substrate applications. In addition, this method has been shown to be useful for the synthesis of drug molecules 6,7-dimethyl-2-phenylquinoxaline (3e) and 2-phenylbenzoquinoxaline (3f). BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 , Figure 2 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 1;

[0021] Figure 3 , Figure 4 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 2;

[0022] Figure 5 , Figure 6 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 3;

[0023] Figure 7 , Figure 8 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 4;

[0024] Fig. 9 , Fig.10 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 5;

[0025] Fig.11 , Fig.12 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 6;

[0026] Fig.13 , Fig.14 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 7;

[0027] Fig.15 , Fig.16 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 8;

[0028] Fig.17 , Fig.18 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 9;

[0029] Fig.19 , Fig. 20 are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 10; DETAILED DESCRIPTION

[0030] 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.

[0031] Example 1

[0032] A quartz reaction tube was set aside, and weighed acetophenone (0.22 mmol), I2 (10 mol%, 0.02 mmol), p-Cl-3CzEPAIPN (1 mol%, 0.002 mmol) and DMSO (3 mL) were added in sequence. After reacting at 120 ° C for 1.5 hours under blue light irradiation, o-phenylenediamine (0.2 mmol) was added and monitored by TCL. After the reaction was completed, it was cooled to room temperature, and a saturated sodium chloride solution was added to the reaction solution, and then extracted with ethyl acetate in small amounts and multiple times. The organic phases were combined and dried over anhydrous magnesium sulfate. After filtering, the crude product was evaporated under reduced pressure to obtain the final product, 2-phenylquinoxaline, which was separated and purified by column chromatography with a yield of 71%.

[0033] The structural characterization data of the obtained target product are shown below:

[0034] 1 H NMR (500MHz, Chloroform-d) δ9.33 (s, 1H), 8.31–8.07 (m, 4H), 7.88–7.70 (m, 2H), 7.55 (d, J = 22.9Hz, 3H) ppm.

[0035] 13 C{1H}NMR(125MHz,Chloroform-d)δ151.9,143.4,142.3,141.6,136.8,130.3,130.2,129.59,129.52,129.13,129.09,127.6ppm.

[0036] HRMS (ESI-TOF) m / z: [M+H] + Calculate for C 14 H 11N2 207.0917; found 207.0922.

[0037] The structure of the target compound is inferred from the above characterization data as follows:

[0038]

[0039] Example 2

[0040] A quartz reaction tube was set aside, and weighed acetophenone (0.22 mmol), I2 (10 mol%, 0.02 mmol), p-Cl-3CzEPAIPN (1 mol%, 0.002 mmol) and DMSO (3 mL) were added in sequence. After reacting at 120 ° C for 1.5 hours under blue light irradiation, 4,5-dichlorobenzene-1,2-diamine (0.2 mmol) was added and monitored by TCL. After the reaction was completed, it was cooled to room temperature, and a saturated sodium chloride solution was added to the reaction solution, and then extracted with ethyl acetate in small amounts and multiple times. The organic phases were combined and dried over anhydrous magnesium sulfate. After filtering, the crude product was evaporated under reduced pressure to obtain the final product, 6,7-dichloro-2-phenylquinoxaline, which was purified by silica gel column with a yield of 88%.

[0041] The structural characterization data of the obtained target product are shown below:

[0042] 1 H NMR (500MHz, Chloroform-d) δ9.30 (s, 1H), 8.27 (s, 1H), 8.25 (s, 1H), 8.17 (d, J = 7.4Hz, 2H), 7.56 (d, J = 7.8Hz, 3H) ppm.

[0043] 13 C{ 1 H}(125MHz,Chloroform-d)δ152.6,144.2,141.0,140.2,135.9,134.9,134.0,130.7,130.1,129.7,129.2,127.5ppm.

[0044] HRMS (ESI-TOF) m / z: [M+H] + Calculate for C 14 H9Cl2N2 275.0137; found 275.0136.

[0045] The structure of the target compound is inferred from the above characterization data as follows:

[0046]

[0047] Example 3

[0048] A quartz reaction tube was set aside, and weighed acetophenone (0.22 mmol), I2 (10 mol%, 0.02 mmol), p-Cl-3CzEPAIPN (1 mol%, 0.002 mmol) and DMSO (3 mL) were added in sequence. After reacting at 120 °C for 1.5 hours under blue light irradiation, 4,5-dibromobenzene-1,2-diamine (0.2 mmol) was added and monitored by TCL. After the reaction was completed, it was cooled to room temperature, and a saturated sodium chloride solution was added to the reaction solution, and then extracted with ethyl acetate in small amounts and multiple times. The organic phases were combined and dried over anhydrous magnesium sulfate. After filtering, the crude product was evaporated under reduced pressure to obtain the crude product, which was finally purified by passing through a silica gel column to obtain the final product 6,7-dibromo-2-phenylquinoxaline with a yield of 72%.

[0049] The structural characterization data of the obtained target product are shown below:

[0050] 1 H NMR (500MHz, Chloroform-d) δ9.31 (s, 1H), 8.46 (s, 1H), 8.41 (s, 1H), 8.18 (d, J = 7.9Hz, 2H), 7.57 (d, J = 7.1Hz, 3H) ppm.

[0051] 13 C{ 1 H}NMR(125MHz,Chloroform-d)δ152.6,144.4,141.5,140.7,135.9,133.6,133.2,130.8,129.3,127.6,127.0,126.0ppm.

[0052] HRMS (ESI-TOF) m / z: [M+H] + Calculate for C 14 H9Br2N2 362.9127; found 362.9124.

[0053] The structure of the target compound is inferred from the above characterization data as follows:

[0054]

[0055] Example 4

[0056] A quartz reaction tube was set aside, and weighed acetophenone (0.22 mmol), I2 (10 mol%, 0.02 mmol), p-Cl-3CzEPAIPN (1 mol%, 0.002 mmol) and DMSO (3 mL) were added in sequence. After reacting at 120 °C for 1.5 hours under blue light irradiation, naphthalene-2,3-diamine (0.2 mmol) was added and monitored by TCL. After the reaction was completed, it was cooled to room temperature, and a saturated sodium chloride solution was added to the reaction solution, and then extracted with ethyl acetate in small amounts and multiple times. The organic phases were combined and dried over anhydrous magnesium sulfate. After filtering, the crude product was evaporated under reduced pressure to obtain the crude product, and finally purified by silica gel column to obtain the final product 2-phenylbenzoquinoxaline with a yield of 70%.

[0057] The structural characterization data of the obtained target product are shown below:

[0058] 1 H NMR (500MHz, Chloroform-d) 9.40 (s, 1H), 8.71 (d, J = 19.9Hz, 2H), 8.27 (d, J = 7.4Hz, 2H), 8.16–8.08 (m, 2H), 7.59 (p, J = 10.3, 8.7Hz, 5H) ppm.

[0059] 13 C{ 1 H}NMR(125MHz,Chloroform-d)δ151.8,144.6,138.8,138.2,136.8,134.2,133.7,130.5,129.2,128.54,128.47,128.0,127.7,127.6,126.9,126.8ppm.

[0060] HRMS (ESI-TOF) m / z: [M+H] + Calculate for C 18 H 13 N2 257.1073; found 257.1081.

[0061] The structure of the target compound is inferred from the above characterization data as follows:

[0062]

[0063] Example 5

[0064] A quartz reaction tube was set aside, and weighed acetophenone (0.22 mmol), I2 (10 mol%, 0.02 mmol), p-Cl-3CzEPAIPN (1 mol%, 0.002 mmol) and DMSO (3 mL) were added in sequence. After reacting at 120 ° C for 1.5 hours under blue light irradiation, 4,5-dimethylbenzene-1,2-diamine (0.2 mmol) was added and monitored by TCL. After the reaction was completed, it was cooled to room temperature, and a saturated sodium chloride solution was added to the reaction solution, and then extracted with ethyl acetate in small amounts and multiple times. The organic phases were combined and dried over anhydrous magnesium sulfate. After filtering, the crude product was evaporated under reduced pressure to obtain the final product, 6,7-dimethyl-2-phenylquinoxaline, which was purified by silica gel column with a yield of 86%.

[0065] The structural characterization data of the obtained target product are shown below:

[0066] 1 H NMR (500MHz, Chloroform-d) δ9.22(s,1H),8.16(d,J=8.0Hz,2H),7.90(s,1H),7.85(s,1H),7.55(t,J=6.3Hz,2H),7.52–7.48(m,1H),2.51(s,6H)ppm.

[0067] 13 C{ 1 H}NMR(125MHz,Chloroform-d)δ151.0,142.4,141.2,140.8,140.5,140.1,137.1,129.8,129.1,128.6,128.1,127.4,20.37,20.34ppm.

[0068] HRMS (ESI-TOF) m / z: [M+H] + Calculate for C 16 H 15 N2 235.1230; found 235.1233.

[0069] The structure of the target compound is inferred from the above characterization data as follows:

[0070]

[0071] Example 6

[0072] A quartz reaction tube was set aside, and weighed p-chloroacetophenone (0.22 mmol), I2 (10 mol%, 0.02 mmol), p-Cl-3CzEPAIPN (1 mol%, 0.002 mmol) and DMSO (3 mL) were added in sequence. After reacting at 120 ° C for 1.5 hours under blue light irradiation, o-phenylenediamine (0.2 mmol) was added and monitored by TCL. After the reaction was completed, it was cooled to room temperature, and a saturated sodium chloride solution was added to the reaction solution, and then extracted with ethyl acetate in small amounts and multiple times. The organic phases were combined and dried over anhydrous magnesium sulfate. After filtering, the crude product was evaporated under reduced pressure to obtain the final product, 2-(4-chlorophenyl)quinoxaline, which was purified by silica gel column with a yield of 73%.

[0073] The structural characterization data of the obtained target product are shown below:

[0074] 1 H NMR (500MHz, Chloroform-d) δ9.29 (s, 1H), 8.25–8.05 (m, 4H), 7.77 (dt, J = 15.4, 7.3Hz, 2H), 7.53 (d, J = 8.3Hz, 2H) ppm.

[0075] 13 C{ 1 H}NMR(125MHz,Chloroform-d)δ150.5,142.8,142.2,141.6,136.5,135.1,130.5,129.8,129.6,129.4,129.1,128.7ppm.

[0076] HRMS (ESI-TOF) m / z: [M+H] + Calculate for C 14 H 10 ClN2 241.0527; found 241.0533.

[0077] The structure of the target compound is inferred from the above characterization data as follows:

[0078]

[0079] Example 7

[0080] A quartz reaction tube was set aside, and weighed p-bromoacetophenone (0.22 mmol), I2 (10 mol%, 0.02 mmol), p-Cl-3CzEPAIPN (1 mol%, 0.002 mmol) and DMSO (3 mL) were added in sequence. After reacting at 120 ° C for 1.5 hours under blue light irradiation, o-phenylenediamine (0.2 mmol) was added and monitored by TCL. After the reaction was completed, it was cooled to room temperature, and a saturated sodium chloride solution was added to the reaction solution, and then extracted with ethyl acetate in small amounts and multiple times. The organic phases were combined and dried over anhydrous magnesium sulfate. After filtering, the crude product was evaporated under reduced pressure to obtain the final product, 2-(4-bromophenyl)quinoxaline, which was purified by silica gel column with a yield of 64%.

[0081] The structural characterization data of the obtained target product are shown below:

[0082] 1 H NMR (500MHz, Chloroform-d) δ9.29 (s, 1H), 8.13 (t, J = 9.0Hz, 2H), 8.08 (d, J = 6.1Hz, 2H), 7.88–7.73 (m, 2H), 7.69 (d, J = 6.2Hz, 2H) ppm.

[0083] 13 C{1H}NMR(125MHz,Chloroform-d)δ150.6,142.8,142.2,141.6,135.6,132.3,130.5,129.8,129.6,129.1,129.0,125.0ppm.

[0084] HRMS(ESI-TOF)m / z:[M+H]+calcd for C 14 H 10 BrN2 285.0022; found 285.0032.

[0085] The structure of the target compound is inferred from the above characterization data as follows:

[0086]

[0087] Example 8

[0088] A quartz reaction tube was set aside, and weighed 3,4-dimethylacetophenone (0.22 mmol), I2 (10 mol%, 0.02 mmol), p-Cl-3CzEPAIPN (1 mol%, 0.002 mmol) and DMSO (3 mL) were added in sequence. After reacting at 120 ° C for 1.5 hours under blue light irradiation, o-phenylenediamine (0.2 mmol) was added and monitored by TCL. After the reaction was completed, it was cooled to room temperature, and a saturated sodium chloride solution was added to the reaction solution, and then extracted with ethyl acetate in small amounts and multiple times. The organic phases were combined and dried over anhydrous magnesium sulfate. After filtering, the crude product was evaporated under reduced pressure to obtain the final product, 2-(3,4-dimethylphenyl)quinoxaline, which was purified by silica gel column with a yield of 65%.

[0089] The structural characterization data of the obtained target product are shown below:

[0090] 1 H NMR(500MHz,Chloroform-d)δ9.31(s,1H),8.15(d,J=8.4Hz,1H),8.11(d,J=8.2Hz,1H),7.99(s,1H),7.91( d,J=5.7Hz,1H),7.81–7.75(m,1H),7.75–7.70(m,1H),7.32(d,J=7.8Hz,1H),2.40(s,3H),2.36(s,3H)ppm.

[0091] 13 C{ 1 H}NMR(125MHz,Chloroform-d)δ152.0,143.4,142.3,141.4,139.2,137.6,134.3,130.4,130.2,129.5,129.2,129.1,128.6,124.9,20.0,19.8ppm.

[0092] HRMS (ESI-TOF) m / z: [M+H] + Calculate for C 16 H 15 N2 235.1230; found 235.1235.

[0093]

[0094] Example 9

[0095] A quartz reaction tube was set aside, and weighed 3,5-dimethylacetophenone (0.22 mmol), I2 (10 mol%, 0.02 mmol), p-Cl-3CzEPAIPN (1 mol%, 0.002 mmol) and DMSO (3 mL) were added in sequence. After reacting at 120 ° C for 1.5 hours under blue light irradiation, o-phenylenediamine (0.2 mmol) was added and monitored by TCL. After the reaction was completed, it was cooled to room temperature, and a saturated sodium chloride solution was added to the reaction solution, and then extracted with ethyl acetate in small amounts and multiple times. The organic phases were combined and dried over anhydrous magnesium sulfate. After filtering, the crude product was evaporated under reduced pressure to obtain the final product, 2-(3,5-dimethylphenyl)quinoxaline, which was purified by silica gel column with a yield of 68%.

[0096] The structural characterization data of the obtained target product are shown below:

[0097] 1 H NMR(500MHz,Chloroform-d)δ9.30(s,1H),8.16(d,J=8.3Hz,1H),8.12(d,J=8.1 Hz,1H),7.79(s,2H),7.75(dd,J=14.9,6.7Hz,2H),7.17(s,1H),2.46(s,6H)ppm.

[0098] 13 C{ 1 H}NMR(125MHz,Chloroform-d)δ151.3,143.7,142.3,141.5,138.8,136.7,131.9,130.2,129.5,129.4,129.1,125.4,21.5.ppm.HRMS(ESI-TOF)m / z:[M+H] + Calculate for C 16 H 15 N2 235.1230; found 235.1231.

[0099]

[0100] Example 10

[0101] A quartz reaction tube was set aside, and weighed 3,4-dichloroacetophenone (0.22 mmol), I2 (10 mol%, 0.02 mmol), p-Cl-3CzEPAIPN (1 mol%, 0.002 mmol) and DMSO (3 mL) were added in sequence. After reacting at 120 ° C for 1.5 hours under blue light irradiation, o-phenylenediamine (0.2 mmol) was added and monitored by TCL. After the reaction was completed, it was cooled to room temperature, and a saturated sodium chloride solution was added to the reaction solution, and then extracted with ethyl acetate in small amounts and multiple times. The organic phases were combined and dried over anhydrous magnesium sulfate. After filtering, the crude product was evaporated under reduced pressure to obtain the final product, 2-(3,4-dimethylphenyl)quinoxaline, which was purified by silica gel column with a yield of 58%.

[0102] The structural characterization data of the obtained target product are shown below:

[0103] 1 H NMR (500MHz, Chloroform-d) δ9.36 (s, 1H), 8.35 (s, 1H), 8.14 (t, J = 8.2Hz, 2H), 8.04 (d, J = 8.6Hz, 1H), 7.80 (p, J = 7.1Hz, 2H), 7.64 (d, J = 8.3Hz, 1H) ppm.

[0104] 13 C{ 1 H}NMR(125MHz,Chloroform-d)δ149.3,142.5,142.1,141.8,136.6,134.6,133.6,131.1,130.7,130.2,129.6,129.4,129.2,126.4ppm.

[0105] HRMS (ESI-TOF) m / z: [M+H] + Calculate for C 14 H9Cl2N2 275.0137; found 275.0144.

[0106]

[0107] 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 visible light-promoted I2-catalyzed C(sp 3 )-H amination reaction to synthesize quinoxaline, characterized in that, The following steps are included: In a glass reaction container, acetophenone, a photocatalyst and I2 are first added in proportion, an organic solvent is added under air atmosphere, o-phenylenediamine is added after magnetic stirring for 1.5 hours under blue light irradiation and 120°C, and the reaction is continued for 3.5 hours to complete the reaction; after extraction, the organic phase is taken and rotary evaporated under reduced pressure to obtain a crude product, and finally the quinoxaline derivative is separated and purified by column chromatography.

2. The synthesis method according to claim 1, characterized in that The chemical reaction equation for the synthesis of quinoxaline is shown below: , where R 1 , R 2 One or more selected from the group consisting of hydrogen, 4,5-dichloro, 4,5-dibromo, 4,5-dimethyl, phenyl, 3,5-dimethyl, 4-chloro, 4-bromo, 3,4-dichloro, 3,4-dimethyl and 3,5-dimethyl.

3. The preparation method according to claim 1 or 2, characterized in that: The organic solvent is one or more of DMSO and DMF.

4. The preparation method according to claim 1 or 2, characterized in that: The photocatalyst is one or more of 3CzEPAIPN, 4-DPAIPN, 3CzMPAIPN, p-Me-3CzMPAIPN, o-Me-3CzMPAIPN, m-Me-3CzMPAIPN, m-Me-3CzEPAIPN, p-Cl-3CzEPAIPN, rhodamine, eosin Y, CeCl3, and FeCl3; the molar ratio of the catalyst to the o-phenylenediamine compound is 1:

100.

5. The preparation method according to claim 1 or 2, characterized in that: The visible light-promoted I2 catalysis of C(sp 3 The reaction time of the method for synthesizing quinoxaline by )-H amination reaction is 5 hours.

6. The preparation method according to claim 1 or 2, characterized in that: The target product quinoxaline derivative is purified by column chromatography, and the eluent is a mixed solvent of petroleum ether and ethyl acetate, and the mixing ratio is: petroleum ether:ethyl acetate = 10:1.

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