A method for electrochemically synthesizing 3-hydroxyalkylquinoxaline-2(1H)-one compounds

Abstract

The present invention discloses a method for electrochemically synthesizing 3-hydroxyalkylquinoxaline-2(1 H )-ketone compounds, under mild electrochemical conditions, quinoxaline-2(1 H )-ketone and aldehyde to synthesize 3-hydroxyalkylquinoxaline-2(1 H )-ketone compounds, that is, aldehydes are reduced under electrochemical conditions to form hydroxyalkyl radicals, which then react with unprotected quinoxaline-2(1 H )-ketone reaction to synthesize a series of 3-hydroxyalkylquinoxaline-2(1 H )-ketone compounds. This method avoids the use of stoichiometric oxidants and heavy metal catalysts, is environmentally friendly, and has high atom economy. Further scale-up studies using a continuous flow electrochemical reactor have shown that it is suitable for industrial large-scale production.

Description

Technical Field

[0001] The present invention relates to electrochemical synthesis technology, in particular to an electrochemical synthesis of 3-hydroxyalkylquinoxaline-2(1 H )-ketone compounds. Background Art

[0002] In organic chemistry, the synthesis and functionalization of nitrogen-containing heterocycles are common and attractive research areas because of their wide applications in medicinal chemistry, agriculture, and materials science. H )-ketone structural unit is a special type of nitrogen heterocyclic scaffold present in biologically active natural products and drug molecules. As the pharmacophore of biologically active compounds, it has multiple reactive sites, which are easy to modify and transform, and can synthesize a series of compounds with different biological activities ( Eur. J. Med. Fabric. 2014, 86 , 122; Eur. J. Med. Fabric. 2015, 97 , 664). In particular, C3-substituted quinoxaline-2(1 H )-one derivatives show a wide range of biological activities. Due to their synthetic uses and potential biological importance, the introduction of functional groups into quinoxaline-2(1 H The C3 position of )-ketone has now become one of the research hotspots in synthetic chemistry.

[0003] C3 substituted quinoxaline-2(1 H )-Keto compounds have a wide range of biological activities, such as anti-tumor activity, antibacterial activity, angiotensin II receptor antagonists and histamine-4 receptor antagonists, etc. ( Eur. J. Med. Fabric. 2011, 46 ,327). In addition, 3-arylquinoxaline-2(1 H )-ketone-derived polymers can be used as semiconductors in materials science ( RSC Adv. 2016, 6 , 22043). 3-Hydroxyalkylquinoxaline-2(1 H )-ketone derivatives show fluorescent properties ( New J . Fabric. 2017, 41 , 10432), so it has synthetic practicality. So far, only two cases of quinoxaline-2(1 H )-ketones, including copper-catalyzed C3-hydroxyalkylation of quinoxaline-2(1 H )-ketone and alcohol to synthesize 3-hydroxyalkylquinoxaline-2(1 H )-one; and protected quinoxaline-2(1 H)-ketone and glyoxylic acid as substrates for the selective synthesis of 3-hydroxyalkylquinoxaline-2(1 H )-ketone. These methods take a long time to react, require the use of stoichiometric oxidants and heavy metal catalysts, are prone to produce metal residues, are difficult to separate from the product, and cause environmental pollution. Therefore, it is necessary to develop green, sustainable, mild, efficient and controllable methods to construct 3-hydroxyalkylquinoxaline-2(1 H )-Keto nitrogen-containing heterocyclic compounds have important theoretical significance and application value. Summary of the invention

[0004] The purpose of the present invention is to provide a method for electrochemically synthesizing 3-hydroxyalkylquinoxaline-2(1 H This method does not require heavy metal catalysts and oxidants or reductants, is green and environmentally friendly, has high atom economy, and has been further scaled up using a continuous flow electrochemical reactor, indicating that it is suitable for industrial large-scale production.

[0005] The technical solution for achieving the purpose of the present invention is:

[0006] An electrochemical synthesis of 3-hydroxyalkylquinoxaline-2(1 H )-ketone compound, the synthetic formula of the compound is as follows:

[0007]

[0008] In the general formula, aldehyde is a fatty aldehyde;

[0009] R 1 , R 2 = alkyl, halogen, etc.;

[0010] The electrolyte is: tetrabutylammonium perchlorate, tetrabutylammonium tetrafluoroborate or tetrabutylammonium iodide, etc.;

[0011] The solvent is: N , N -dimethylformamide or N , N - dimethylacetamide;

[0012] The catalyst is: ferrocene or 2,2,6,6-tetramethylpiperidinyl oxide.

[0013] The electrochemical synthesis of 3-hydroxyalkylquinoxaline-2(1 H )-ketone compound is:

[0014] 0.4 mmol of quinoxaline-2(1H)-one compound, 2.4 mmol of fatty aldehyde, 0.6 mmol of electrolyte, and 0.08 mmol of catalyst were added to a 10 mL three-necked round-bottom flask respectively;

[0015] Then, 6.0 mL of solvent was added to dissolve, and a platinum sheet (1 cm x 1 cm) was used as the anode and a graphite rod (Φ 6 mm) was used as the cathode. The reaction was stirred at 45 °C and a constant current of 15 mA was used. The reaction progress was monitored by thin layer chromatography. The reaction time was 5 to 6 hours until the substrate was completely consumed.

[0016] After the reaction was completed, the reaction solution was extracted with ethyl acetate and water, the combined organic phase solution was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure, and the concentrate was purified by 300-400 mesh silica gel column chromatography to obtain the target product.

[0017] The column chromatography purification uses petroleum ether / ethyl acetate as eluent, wherein the volume ratio of petroleum ether / ethyl acetate is 30:1.

[0018] During synthesis, raw materials can be added according to the multiples of the raw material ratio in the above synthesis method.

[0019] C3 substituted quinoxaline-2(1 H )-Keto compounds have a wide range of biological activities ( Biochem. Pharmacol. 2003, 65 , 59), among which 3-hydroxyalkylquinoxaline-2(1 H )-ketone derivatives show fluorescent properties ( New J. Chem. 2017, 41 , 10432), so it has synthetic practicality.

[0020] The synthesis method of the present invention is to synthesize quinoxaline-2(1 H )-ketone compounds and aldehydes to synthesize 3-hydroxyalkylquinoxaline-2(1 H )-ketone compounds. The synthesis method of the present invention avoids the use of stoichiometric oxidants and heavy metal catalysts, is environmentally friendly, and has high atom economy. Further scale-up studies using a continuous flow electrochemical reactor show that it is suitable for industrial large-scale production. DETAILED DESCRIPTION

[0021] The present invention is further described below with reference to the embodiments, but is not intended to be limiting of the present invention.

[0022] Embodiment 1:

[0023] 3-(Cyclohexyl(hydroxy)methyl)quinoxaline-2(1 HPreparation and characterization of )-ketone (3aa):

[0024]

[0025] 3aa

[0026] 0.4 mmol of quinoxaline-2(1 H )-ketone, 2.4 mmol cyclohexylcarboxaldehyde, 0.6 mmol tetrabutylammonium perchlorate, and 0.08 mmol ferrocene were placed in a 10 mL three-necked round-bottom flask;

[0027] Then add 6.0 mL of N,N -dimethylformamide solvent dissolution, using a platinum sheet (1 cm x 1 cm) as the anode and a graphite rod (Φ 6 mm) as the cathode, stirring the reaction at 45 °C with a constant current of 15 mA until the substrate is completely consumed (monitored by thin layer chromatography, reaction time is 5 hours);

[0028] After the reaction was completed, the reaction solution was extracted with ethyl acetate and water, and the combined organic phase solution was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (300-400 mesh silica gel, petroleum ether / ethyl acetate = 30:1) to obtain the target product 3aa.

[0029] The product is characterized by:

[0030] white solid (78.5 mg, 76%). mp: 144 - 145℃. 1 H NMR (600 MHz, DMSO- d 6)δ12.43 (s, 1H), 7.77 (dd, J = 8.1, 1.3 Hz, 1H), 7.52 - 7.49 (m, 1H), 7.30 -7.28 (m, 2H), 4.81 (d, J = 6.8 Hz, 1H), 4.67 (t, J = 6.2 Hz, 1H), 1.96 - 1.87(m, 1H), 1.66 - 1.55 (m, 4H), 1.4 - 1.42 (m, 1H), 1.20 - 1.05 (m, 5H). 13 C NMR (150 MHz, DMSO- d6)δ 161.93, 154.24, 131.80, 131.28, 130.05, 128.39, 123.37,115.40. HRMS(m / z) [ESI]: calculated for C 15 H 19 N2O2 + m / z [M+H] + : 259.1441, found259.1443.

[0031] Embodiment 2:

[0032] Preparation and characterization of 3-(cyclopropyl(hydroxy)methyl)quinoxaline-2(1H)-one (3ab):

[0033]

[0034] 3ab

[0035] 0.4 mmol of quinoxaline-2(1 H )-ketone, 2.4 mmol cyclopropylcarboxaldehyde, 0.6 mmol tetrabutylammonium perchlorate, and 0.08 mmol ferrocene were placed in a 10 mL three-necked round-bottom flask;

[0036] Then add 6.0 mL of N , N -Dimethylacetamide solvent was dissolved, a platinum sheet (1 cm x 1 cm) was used as the anode, a graphite rod (Φ 6 mm) was used as the cathode, and the reaction was stirred at 45 °C with a constant current of 15 mA until the substrate was completely consumed (monitored by thin layer chromatography, reaction time was 6 hours);

[0037] After the reaction was completed, the reaction solution was extracted with ethyl acetate and water, and the combined organic phase solution was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (300-400 mesh silica gel, petroleum ether / ethyl acetate = 30:1) to obtain the target product 3ab.

[0038] The product is characterized by:

[0039] yellow solid (58.0 mg, 67%). mp: 146 - 147℃. 1 H NMR (400 MHz, DMSO- d 6)δ 12.45 (s, 1H), 7.79 - 7.77 (m, 1H), 7.54-7.50 (m, 1H), 7.32 - 7.28 (m, 2H), 5.00 (d,J = 6.5 Hz, 1H), 4.44 (t, J = 6.8 Hz, 1H), 1.38 - 1.31 (m, 1H), 0.42- 0.35 (m, 4H). 13 C NMR (100 MHz, DMSO- d 6)δ 161.81, 154.21, 131.87, 131.29,130.06, 128.39, 123.34, 115.35, 71.02, 15.31, 2.39, 1.67. HRMS(m / z) [ESI]:calculated for C 12 H 13 N2O2 + m / z [M+H] + : 217.0972, found 217.0983.

[0040] Embodiment 3:

[0041] 3-(1-Hydroxyoctyl)quinoxaline-2(1 H Preparation and characterization of )-ketone (3ac):

[0042]

[0043] 3ac

[0044] 0.4 mmol of quinoxaline-2(1 H )-ketone, 2.4 mmol n-octanal, 0.6 mmol tetrabutylammonium perchlorate, and ferrocene (0.08 mmol) were placed in a 10 mL three-necked round-bottom flask;

[0045] Then add 6.0 mL of N,N -dimethylformamide solvent dissolution, using a platinum sheet (1 cm x 1 cm) as the anode and a graphite rod (Φ 6 mm) as the cathode, stirring the reaction at 45 °C with a constant current of 15 mA until the substrate is completely consumed (monitored by thin layer chromatography, reaction time is 5 hours);

[0046] After the reaction was completed, the reaction solution was extracted with ethyl acetate and water, and the combined organic phase solution was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (300-400 mesh silica gel, petroleum ether / ethyl acetate = 30:1) to obtain the target product 3ac.

[0047] The product is characterized by:

[0048] white solid (75.7 mg, 69%). mp: 135 - 136℃. 1 H NMR (400 MHz, DMSO- d 6)δ12.42 (s, 1H), 7.78 - 7.76 (m, 1H), 7.53 - 7.48 (m, 1H), 7.31 - 7.27 (m, 2H), 4.92 - 4.85 (m, 2H), 1.86 - 1.78 (m, 1H), 1.65 - 1.56 (m, 1H), 1.40 - 1.21 (m, 10H), 0.85 - 0.81 (m, 3H). 13 C NMR (100 MHz, DMSO- d 6)δ 162.35, 154.04,131.86, 131.26, 129.93, 128.31, 123.28, 115.33, 68.54, 34.58, 31.26, 28.94,28.66, 25.28, 22.09, 13.95. HRMS (m / z) [ESI]: calculated for C 16 H 23 N2O2 + m / z [M+H] + : 275.1754, found 275.1757.

[0049] Embodiment 4:

[0050] 3-(1-Hydroxydecyl)quinoxaline-2(1 H Preparation and characterization of )-ketone (3ad):

[0051]

[0052] 3ad

[0053] 0.4 mmol of quinoxaline-2(1 H )-ketone, 2.4 mmol decanal, 0.6 mmol tetrabutylammonium perchlorate, and 0.08 mmol ferrocene were placed in a 10 mL three-necked round-bottom flask;

[0054] Then add 6.0 mL of N,N-dimethylformamide solvent, using a platinum sheet (1 cm x 1 cm) as the anode and a graphite rod (Φ 6 mm) as the cathode, stirring and reacting at 45 °C with a constant current of 15 mA until the substrate is completely consumed (monitored by thin layer chromatography, reaction time is 5 hours);

[0055] After the reaction was completed, the reaction solution was extracted with ethyl acetate and water, and the combined organic phase solution was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (300-400 mesh silica gel, petroleum ether / ethyl acetate = 30:1) to obtain the target product 3ad.

[0056] The product is characterized by:

[0057] white solid (79.8 mg, 66%). mp: 152 - 152℃. 1 H NMR (600 MHz, DMSO- d 6)δ12.43 (s, 1H), 7.78 - 7.76 (m, 1H), 7.51 (td, J = 7.6, 1.4 Hz, 1H), 7.31 -7.28 (m, 2H), 4.92 (s, 1H), 4.87 (dd, J 0.83 (t, J =6.9 Hz, 3H). 13 C NMR (150 MHz, DMSO- d 6)δ 162.37,154.06, 131.89, 131.27, 129.94, 128.32, 123.28, 115.35, 68.52, 34.57, 31.31,29.00, 28.97, 28.71, 25.27, 22.12, 13.98. HRMS (m / z) [ESI]: calculated forC 18 H 27 N2O2 + m / z [M+H] + : 303.2067, found 303.2066.

[0058] Embodiment 5:

[0059] 3-(1-Hydroxydodecyl)quinoxaline-2(1 H Preparation and characterization of )-ketone (3ae):

[0060]

[0061] 3ae

[0062] 0.4 mmol of quinoxaline-2(1 H )-ketone, 2.4 mmol n-dodecanal, 0.6 mmol tetrabutylammonium perchlorate, and 0.08 mmol ferrocene were placed in a 10 mL three-necked round-bottom flask;

[0063] Then add 6.0 mL of N,N -dimethylformamide solvent dissolution, using a platinum sheet (1 cm x 1 cm) as the anode and a graphite rod (Φ 6 mm) as the cathode, stirring the reaction at 45 °C with a constant current of 15 mA until the substrate is completely consumed (monitored by thin layer chromatography, reaction time is 5 hours);

[0064] After the reaction was completed, the reaction solution was extracted with ethyl acetate and water, and the combined organic phase solution was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (300-400 mesh silica gel, petroleum ether / ethyl acetate = 30:1) to obtain the target product 3ae.

[0065] The product is characterized by:

[0066] white solid (84.6 mg, 64%). mp: 145 - 146℃. 1 H NMR (400 MHz, DMSO- d 6)δ12.42 (s, 1H), 7.76 (dt, J = 7.8, 1.3 Hz, 1H), 7.52-7.48 (m, 1H), 7.31-7.27(m, 2H), 4.92 - 4.85 (m, 2H), 1.86 - 1.77 (m, 1H), 1.64 - 1.56 (m, 1H), 1.35-1.20 (m, 18H), 0.85 - 0.81 (m, 3H). 13 C NMR (100 MHz, DMSO- d6)δ 162.33, 154.04,131.87, 131.26, 129.92, 128.31, 123.27, 115.33, 68.55, 34.58, 31.32, 29.06,29.03, 29.01, 29.00, 28.98, 28.73, 25.26, 22.12, 13.96. HRMS (m / z) [ESI]:calculated for C 20 H 31 N2O2 + m / z [M+H] + : 331.2380, found 331.2388.

[0067] Embodiment 6:

[0068] 3-(1-Hydroxy-3-methylbutyl)quinoxaline-2(1 H Preparation and characterization of )-ketone (3af):

[0069]

[0070] 3af

[0071] 0.4 mmol of quinoxaline-2(1 H )-ketone, 2.4 mmol isovaleraldehyde, 0.6 mmol tetrabutylammonium perchlorate, and 0.08 mmol 2,2,6,6-tetramethylpiperidinoxide were placed in a 10 mL three-necked round-bottom flask;

[0072] Then add 6.0 mL of N,N -dimethylformamide solvent dissolution, using a platinum sheet (1 cm x 1 cm) as the anode and a graphite rod (Φ 6 mm) as the cathode, stirring the reaction at 45 °C with a constant current of 15 mA until the substrate is completely consumed (monitored by thin layer chromatography, reaction time is 5 hours);

[0073] After the reaction was completed, the reaction solution was extracted with ethyl acetate and water, and the combined organic phase solution was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (300-400 mesh silica gel, petroleum ether / ethyl acetate = 30:1) to obtain the target product 3af.

[0074] The product is characterized by:

[0075] white solid (53.9 mg, 58%). mp: 150 - 151℃. 1 H NMR (600 MHz, DMSO-d 6)δ12.43 (s, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.51 - 7.48 (m, 1H), 7.31 - 7.27 (m,2H), 4.97 (dd, J = 9.1 Hz, 4.0, 1H), 4.91 (s, 1H), 1.88 - 1.81 (m, 1H), 1.61- 1.52 (m, 2H), 0.94 (d, J = 6.6 Hz, 3H), 0.90 (d, J = 6.7 Hz, 3H). 13 C NMR (150 MHz, DMSO- d 6)δ 162.68, 154.04, 131.90, 131.33, 129.92, 128.31, 123.28,115.36, 66.91, 43.73, 24.37, 23.55, 21.70. HRMS(m / z) [ESI]: calculated forC 13 H 17 N2O2 + m / z [M+H] + : 233.1285, found 233.1287.

[0076] Embodiment 7:

[0077] 3-(1-Hydroxy-3,3-dimethylbutyl)quinoxaline-2(1 H Preparation and characterization of )-ketone (3ag):

[0078]

[0079] 3ag

[0080] 0.4 mmol of quinoxaline-2(1 H )-ketone, 2.4 mmol 3,3-dimethylbutanal, 0.6 mmol tetrabutylammonium tetrafluoroborate, and 0.08 mmol ferrocene were placed in a 10 mL three-necked round-bottom flask;

[0081] Then add 6.0 mL of N , NThe solution was dissolved in dimethylacetamide solvent, a platinum sheet (1 cm x 1 cm) was used as the anode, a graphite rod (Φ 6 mm) was used as the cathode, and the reaction was stirred at 45 °C with a constant current of 15 mA until the substrate was completely consumed (monitored by thin layer chromatography, reaction time was 5 hours);

[0082] After the reaction was completed, the reaction solution was extracted with ethyl acetate and water, and the combined organic phase solution was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (300-400 mesh silica gel, petroleum ether / ethyl acetate = 30:1) to obtain the target product 3ag.

[0083] The product is characterized by:

[0084] yellow (64.0 mg, 65%). mp: 169-170℃. dr 1:1.1, as an inseparable diastereomeric mixture. 1 H NMR (600 MHz, DMSO- d 6)δ = 7.76 (dd, J = 8.1, 1.4 Hz,1H), 7.51 - 7.48 (m, 1H), 7.32 - 7.27 (m, 2H), 5.07 (d, J = 3.4 Hz, 0.48H), 4.83 (s, 1H), 5.06 (d, J = 3.4 Hz, 0.52H) 1.75 (dd, J = 14.0, 3.4 Hz, 1H),1.49 (dd, J = 14.0, 8.4 Hz, 1H), 0.96 (s, 9H). 13 C NMR (150 MHz, DMSO- d 6)δ162.97, 154.02, 131.99, 131.30, 129.88, 128.28, 123.26, 115.40, 66.59, 47.89,30.40, 30.17. HRMS(m / z) [ESI]: calculated for C 14 H 19 N2O2 + m / z [M+H] + : 247.1441, found 247.1442.

[0085] Embodiment 8:

[0086] 3-(Cyclohexane-3-ene-1-(hydroxy)methyl)quinoxaline-2(1 H Preparation and characterization of )-ketone (3ah):

[0087]

[0088] 3ah

[0089] 0.4 mmol of quinoxaline-2(1 H )-ketone, 2.4 mmol 3-cyclohexene-1-carbaldehyde, 0.6 mmol tetrabutylammonium iodide, and 0.08 mmol ferrocene were placed in a 10 mL three-necked round-bottom flask;

[0090] Then add 6.0 mL of N,N -dimethylformamide solvent dissolution, using a platinum sheet (1 cm x 1 cm) as the anode and a graphite rod (Φ 6 mm) as the cathode, stirring the reaction at 45 °C with a constant current of 15 mA until the substrate is completely consumed (monitored by thin layer chromatography, reaction time is 5 hours);

[0091] After the reaction was completed, the reaction solution was extracted with ethyl acetate and water, and the combined organic phase solution was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (300-400 mesh silica gel, petroleum ether / ethyl acetate = 30:1) to obtain the target product 3ah.

[0092] The product is characterized by:

[0093] white solid (68.7 mg, 67%). mp: 134 - 135℃. dr 1:1, as aninseparable diastereomeric mixture. 1 H NMR (600 MHz, DMSO- d 6)δ = 12.45 (d, J =7.8, 1H), 7.79 (dd, J = 8.1, 3.1 Hz, 1H), 7.52 (t, J = 7.7 Hz, 1H), 7.32-7.29(m, 2H), 5.64- 5.57 (m, 2H), 4.95 (d, J = 30.6 Hz, 1H), 4.80 (d, J = 5.9 Hz,0.5H), 4.73 (d, J= 6.6 Hz, 0.5H) 2.28 - 2.15 (m, 1H), 2.04 - 1.80 (m, 5H), 1.45.1.27 (m, 1H). 13 C NMR (150 MHz, DMSO- d 6)δ 161.56, 161.54, 154.30, 154.20,131.84, 131.32, 131.24, 130.11, 130.09, 128.43, 128.41, 126.93, 126.51,126.34, 123.36, 72.31, 71.90, 37.33, 36.97, 27.98, 25.93, 25.60, 24.81,24.62, 23.36. HRMS(m / z) [ESI]: calculated for C 15 H 17 N2O2 + m / z [M+H] + : 257.1285, found 257.1282.

[0094] Embodiment 9:

[0095] 3-(1-Hydroxy-3-phenylpropyl)quinoxaline-2(1 H Preparation and characterization of )-ketone (3ai):

[0096]

[0097] 3ai

[0098] 0.4 mmol of quinoxaline-2(1 H )-ketone, 2.4 mmol phenylpropanaldehyde, 0.6 mmol tetrabutylammonium perchlorate, and 0.08 mmol ferrocene were placed in a 10 mL three-necked round-bottom flask;

[0099] Then add 6.0 mL of N,N -dimethylformamide solvent dissolution, using a platinum sheet (1 cm x 1 cm) as the anode and a graphite rod (Φ 6 mm) as the cathode, stirring the reaction at 45 °C with a constant current of 15 mA until the substrate is completely consumed (monitored by thin layer chromatography, reaction time is 6 hours);

[0100] After the reaction was completed, the reaction solution was extracted with ethyl acetate and water, and the combined organic phase solution was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (300-400 mesh silica gel, petroleum ether / ethyl acetate = 30:1) to obtain the target product 3ai.

[0101] The product is characterized by:

[0102] white solid (80.7 mg, 72%). mp: 158 - 159℃. 1 H NMR (400 MHz, DMSO- d 6)δ12.41 (s, 1H), 7.78 (dd, J = 8.5, 1.3 Hz, 1H), 7.51 (td, J = 7.5, 1.4 Hz,1H), 7.32 - 7.12 (m, 9H), 5.12 (d, J = 6.4 Hz, 1H), 4.94 - 4.89 (m, 1H), 2.82- 2.69 (m, 2H), 2.19 - 2.10 (m, 1H), 2.00 - 1.90 (m, 1H). 13 C NMR (100 MHz, DMSO- d 6)δ 161.94, 154.05, 141.97, 131.94, 131.29, 129.99, 128.38, 128.30,128.24, 125.63, 123.28, 115.34, 68.07, 36.20, 31.42. HRMS(m / z) [ESI]:calculated for C 17 H 17 N2O2 + m / z [M+H] + : 281.1285, found 281.1294.

[0103] Embodiment 10:

[0104] 3-(1,7-dihydroxy-3,7-dimethyloctyl)quinoxaline-2(1 H Preparation and characterization of )-ketone (3aj):

[0105]

[0106] 3aj

[0107] 0.4 mmol of quinoxaline-2(1 H )-ketone, 2.4 mmol hydroxycitronellal, 0.6 mmol tetrabutylammonium perchlorate, and 0.08 mmol ferrocene were placed in a 10 mL three-necked round-bottom flask;

[0108] Then add 6.0 mL of N,N -dimethylformamide solvent dissolution, using a platinum sheet (1 cm x 1 cm) as the anode and a graphite rod (Φ 6 mm) as the cathode, stirring the reaction at 45 °C with a constant current of 15 mA until the substrate is completely consumed (monitored by thin layer chromatography, reaction time is 5 hours);

[0109] After the reaction was completed, the reaction solution was extracted with ethyl acetate and water, and the combined organic phase solution was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (300-400 mesh silica gel, petroleum ether / ethyl acetate = 30:1) to obtain the target product 3aj.

[0110] The product is characterized by:

[0111] white solid (93.0 mg, 73%). mp: 136 - 137℃. 1 H NMR (600 MHz, DMSO- d 6)δ12.42 (s, 1H), 7.77 (dd, J = 8.0, 1.4 Hz, 1H), 7.51-7.48 (m, 1H), 7.31 - 7.28(m, 2H), 4.99 (dd, J = 9.6, 3.3 Hz, 1H), 4.89 (s, 1H), 4.05 (s, 1H), 1.80-1.74 (m, 1H), 1.63-1.58 (m, 1H), 1.52 -1.48 (m, 1H), 1.31 - 1.25 (m, 4H),1.21 - 1.20 (m, 1H), 1.16 - 1.12 (m, 1H), 1.03 (d, J = 1.5 Hz, 6H), 0.94 (d, J = 6.6 Hz, 3H). 13 C NMR (150 MHz, DMSO- d6)δ 162.87, 154.12, 154.01, 131.91,131.33, 129.89, 128.29, 123.29, 115.37, 68.80, 66.66, 43.97, 41.92, 38.19,29.35, 29.32, 28.90, 21.30, 19.02. HRMS(m / z) [ESI]: calculated for C 18 H 27 N2O3 + m / z [M+H] + : 319.2016, found 319.2015.

[0112] Embodiment 11:

[0113] 3-(1-Hydroxy-3,7-dimethyloctane-6-ene-1-methyl)quinoxaline-2(1 H Preparation and characterization of )-ketone (3ak):

[0114]

[0115] 3ak

[0116] 0.4 mmol of quinoxaline-2(1 H )-ketone, 2.4 mmol citronellal, 0.6 mmol tetrabutylammonium perchlorate, and 0.08 mmol ferrocene were placed in a 10 mL three-necked round-bottom flask;

[0117] Then add 6.0 mL of N,N -dimethylformamide solvent dissolution, using a platinum sheet (1 cm x 1 cm) as the anode and a graphite rod (Φ 6 mm) as the cathode, stirring the reaction at 45 °C with a constant current of 15 mA until the substrate is completely consumed (monitored by thin layer chromatography, reaction time is 5 hours);

[0118] After the reaction was completed, the reaction solution was extracted with ethyl acetate and water, and the combined organic phase solution was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (300-400 mesh silica gel, petroleum ether / ethyl acetate = 30:1) to obtain the target product 3ak.

[0119] The product is characterized by:

[0120] white solid (88.9 mg, 74%). mp: 151 - 152℃. dr 1.1:1, as aninseparable diastereomeric mixture. 1 H NMR(600 MHz, DMSO- d 6)δ 12.42 (s, 1H),7.76 (dd, J = 7.4, 2.8 Hz, 1H), 7.50 (t, J = 7.7 Hz, 1H), 7.31 - 7.28 (m,2H), 5.08 - 5.0 (m, 1H), 5.00 (d, J = 4.3 Hz, 0.52H), 4.98 (d, J = 4.4 Hz,0.48H), 2.03 - 1.90z (m, 2H), 1.81 - 1.74 (m, 1H), 1.68-1.64 (m, 1H), 1.60(d, J = 4.3 Hz, 3H), 1.54 (d, J = 5.4 Hz, 3H), 1.46 - 1.44 (m, 1H), 1.27 -1.12 (m, 2H), 0.94 (d, J = 6.6 Hz, 1H), 0.90 (d, J = 6.7 Hz, 2H). 13 C NMR(150MHz, DMSO- d 6)δ 162.75, 162.62, 154.14, 154.06, 131.98, 131.95, 131.36,131.33, 130.42, 130.37, 129.92, 129.88, 128.31, 128.28, 124.79, 124.71,123.25, 115.39, 66.91, 66.70, 42.09, 41.86, 37.51, 35.89, 28.84, 28.57,25.52, 25.51, 25.06, 24.71, 20.43, 18.88, 17.52. HRMS(m / z) [ESI]: calculatedfor C 18 H 25 N2O2 + m / z [M+H] +: 301.1911, found 301.1914.

[0121] Embodiment 12:

[0122] 3-(3-(4-(tert-butyl)phenyl)-1-hydroxy-2-methylpropyl)quinoxaline-2(1 H Preparation and characterization of )-ketone (3al):

[0123]

[0124] 3al

[0125] 0.4 mmol of quinoxaline-2(1 H )-ketone, 2.4 mmol lily of the valley aldehyde, 0.6 mmol tetrabutylammonium perchlorate, and 0.08 mmol ferrocene were placed in a 10 mL three-necked round-bottom flask;

[0126] Then add 6.0 mL of N,N -dimethylformamide solvent dissolution, using a platinum sheet (1 cm x 1 cm) as the anode and a graphite rod (Φ 6 mm) as the cathode, stirring the reaction at 45 °C with a constant current of 15 mA until the substrate is completely consumed (monitored by thin layer chromatography, reaction time is 5 hours);

[0127] After the reaction was completed, the reaction solution was extracted with ethyl acetate and water, and the combined organic phase solution was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (300-400 mesh silica gel, petroleum ether / ethyl acetate = 30:1) to obtain the target product 3a1.

[0128] The product is characterized by:

[0129] white solid (99.5 mg, 71%). mp: 165 - 166℃. 1 H NMR (400 MHz, DMSO- d 6)δ12.34 (s, 1H), 7.77 (dd, J = 8.1, 1.2 Hz, 1H), 7.52 - 7.48 (m, 1H), 7.31 -7.25 (m, 2H), 7.15 - 7.13 (m, 2H), 7.00 - 6.98 (m, 2H), 5.09 (d, J = 6.4 Hz,1H), 4.72 (t, J = 6.3 Hz, 1H), 2.87 (dd, J= 13.3, 4.6 Hz, 1H), 2.31 (dd, J =13.4, 8.8 Hz, 1H), 1.22 (s, 1H), 1.19 (s, 9H), 0.79 (d, J = 6.8 Hz, 3H). 13 CNMR (100 MHz, DMSO- d 6)δ 161.57, 154.14, 147.60, 137.55, 131.83, 131.22,129.95, 128.84, 128.30, 124.61, 123.24, 115.30, 72.65, 38.39, 36.64, 33.94,31.19, 16.68. HRMS (m / z) [ESI]: calculated for C 22 H 27 N2O2 + m / z [M+H] + :351.2067, found 351.2066.

[0130] Embodiment 13:

[0131] 3-(Cyclohexyl(hydroxy)methyl)-6-methoxyquinoxaline-2(1 H Preparation and characterization of )-ketone (3ba):

[0132]

[0133] 3ba

[0134] 0.4 mmol of 6-methoxyquinoxaline-2(1 H )-ketone, 2.4 mmol cyclohexylcarboxaldehyde, 0.6 mmol tetrabutylammonium perchlorate, and 0.08 mmol ferrocene were placed in a 10 mL three-necked round-bottom flask;

[0135] Then add 6.0 mL of N,N -dimethylformamide solvent dissolution, using a platinum sheet (1 cm x 1 cm) as the anode and a graphite rod (Φ 6 mm) as the cathode, stirring the reaction at 45 °C with a constant current of 15 mA until the substrate is completely consumed (monitored by thin layer chromatography, reaction time is 5 hours);

[0136] After the reaction was completed, the reaction solution was extracted with ethyl acetate and water, and the combined organic phase solution was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (300-400 mesh silica gel, petroleum ether / ethyl acetate = 30:1) to obtain the target product 3ba.

[0137] The product is characterized by:

[0138] white solid (93.4 mg, 81%). mp: 136 - 137℃. 1 H NMR (400 MHz, DMSO- d 6)δ12.40 (s, 1H), 7.30 (d, J = 2.8 Hz, 1H), 7.24 (d, J = 8.9 Hz, 1H), 7.16 (dd, J = 8.9, 2.8 Hz, 1H), 5.29 - 4.78 (m, 1H), 4.67 (d, J = 5.9 Hz, 1H), 3.81 (s,3H), 1.95 - 1.89 (m, 1H), 1.66 - 1.57 (m, 4H), 1.46 - 1.43 (m, 1H), 1.21 -1.05 (m, 5H). 13 C NMR (100 MHz, DMSO- d 6)δ 162.15, 155.41, 153.87, 131.93,125.93, 119.34, 116.30, 109.88, 72.98, 55.60, 41.39, 29.56, 27.29, 26.08,25.89, 25.59. HRMS(m / z) [ESI]: calculated for C 16 H 20 N2NaO3 + m / z [M+Na] + :311.1366, found 311.1365.

[0139] Embodiment 14:

[0140] 3-(Cyclohexyl(hydroxy)methyl)-6-chloro-quinoxaline-2(1 H Preparation and characterization of )-ketone (3ca):

[0141]

[0142] 3ca

[0143] 0.4 mmol of 6-chloro-quinoxaline-2(1 H )-ketone, 2.4 mmol cyclohexylcarboxaldehyde, 0.6 mmol tetrabutylammonium perchlorate, and 0.08 mmol ferrocene were placed in a 10 mL three-necked round-bottom flask;

[0144] Then add 6.0 mL of N,N -dimethylformamide, using a platinum sheet (1 cm x 1 cm) as the anode and a graphite rod (Φ6 mm) as the cathode, stirring the reaction at 45 °C with a constant current of 15 mA until the substrate is completely consumed (TLC monitoring, reaction time is 5 hours);

[0145] After the reaction was completed, the reaction solution was extracted with ethyl acetate and water, and the combined organic phase solution was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (300-400 mesh silica gel, petroleum ether / ethyl acetate = 30:1) to obtain the target product 3ca.

[0146] The product is characterized by:

[0147] yellow solid (78.5 mg, 67%). mp: 159 - 160℃. 1 H NMR (600 MHz, DMSO- d 6)δ 12.49 (s, 1H), 7.78 (d, J = 8.5 Hz, 1H), 7.33 - 7.30 (m, 2H), 4.85 (d, J =6.6 Hz, 1H), 4.66 (d, J = 4.2 Hz, 1H), 1.93-1.87 (m, 1H), 1.67 - 1.57 (m,4H), 1.46 - 1.40 (m, 1H), 1.22 - 1.07 (m, 5H). 13 C NMR (150 MHz, DMSO- d 6)δ162.48, 153.99, 134.02, 132.92, 130.07, 129.68, 123.41, 114.65, 72.75, 41.33,29.47, 27.35, 26.06, 25.86, 25.57. HRMS(m / z) [ESI]: calculated for C 15 H18 ClN2O2 + m / z [M+H] + : 293.1051, found 293.1051.

[0148] Embodiment 15:

[0149] 3-(Cyclohexyl(hydroxy)methyl)-6,7-dimethylquinoxaline-2(1 H Preparation and characterization of )-ketone (3da):

[0150]

[0151] 3da

[0152] 0.4 mmol 6,7-dimethylquinoxaline-2(1 H )-ketone, 2.4 mmol cyclohexylcarboxaldehyde, 0.6 mmol tetrabutylammonium perchlorate, and 0.08 mmol ferrocene were placed in a 10 mL three-necked round-bottom flask;

[0153] Then add 6.0 mL of N,N -dimethylformamide, using a platinum sheet (1 cm x 1 cm) as the anode and a graphite rod (Φ6 mm) as the cathode, stirring the reaction at 45 °C with a constant current of 15 mA until the substrate is completely consumed (TLC monitoring, reaction time is 5 hours);

[0154] After the reaction was completed, the reaction solution was extracted with ethyl acetate and water, and the combined organic phase solution was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (300-400 mesh silica gel, petroleum ether / ethyl acetate = 30:1) to obtain the target product 3da.

[0155] The product is characterized by:

[0156] white solid (90.5 mg, 79%). mp: 133 - 134℃. 1 H NMR (600 MHz, DMSO- d 6)δ12.30 (s, 1H), 7.55 (s, 1H), 7.06 (s, 1H), 4.75 (d, J = 6.8 Hz, 1H), 4.63 (t, J= 6.4 Hz, 1H), 2.30 (s, 3H), 2.28 (s, 3H), 1.92-1.87 (m, 1H), 1.67 - 1.57(m, 3H), 1.43-1.41 (m, 1H), 1.18 - 1.04 (m, 5H). 13 C NMR (150 MHz, DMSO- d 6)δ160.43, 154.34, 139.59, 132.08, 129.80, 129.78, 128.29, 115.40, 72.91, 41.40,29.55, 27.37, 26.13, 25.92, 25.63, 19.83, 19.00. HRMS (m / z) [ESI]: calculated for C 17 H 22 KN2O2 + m / z [M+K] + : 325.1313, found 325.1309.

[0157] Embodiment 16:

[0158] 3-(Cyclohexyl(hydroxy)methyl)-1-methylquinoxaline-2(1 H Preparation and characterization of )-ketone (3ea):

[0159]

[0160] 3ea

[0161] 0.4 mmol 1-methylquinoxaline-2(1 H )-ketone, 2.4 mmol cyclohexylcarboxaldehyde, 0.6 mmol tetrabutylammonium perchlorate, and 0.08 mmol ferrocene were placed in a 10 mL three-necked round-bottom flask;

[0162] Then add 6.0 mL of N,N -dimethylformamide solvent dissolution, using a platinum plate (1 cm x 1 cm) as the anode and a graphite rod (Φ 6 mm) as the cathode, stirring the reaction at 45 °C with a constant current of 15 mA until the substrate is completely consumed (monitored by thin layer chromatography, reaction time is 5 hours);

[0163] After the reaction was completed, the reaction solution was extracted with ethyl acetate and water, and the combined organic phase solution was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (300-400 mesh silica gel, petroleum ether / ethyl acetate = 30:1) to obtain the target product 3ea.

[0164] The product is characterized by:

[0165] white solid (81.7 mg, 75%). mp: 118 - 119℃. 1 H NMR (600 MHz, DMSO- d 6)δ7.83 (dd, J = 7.9, 1.5 Hz, 1H), 7.64 - 7.61 (m, 1H), 7.56 (dd, J = 8.4, 1.3Hz, 1H), 7.40 - 7.37 (m, 1H), 4.82 (d, J = 6.7 Hz, 1H), 4.71 (t, J = 6.0 Hz,1H), 3.63 (s, 3H), 1.95 - 1.90 (m, 1H), 1.60-1.56 (m, 4H), 1.45 - 1.43 (m,1H), 1.21 - 1.06 (m, 5H). 13 C NMR (150 MHz, DMSO- d 6)δ 160.40, 153.56, 133.00,131.54, 130.29, 129.11, 123.53, 114.81, 73.27, 41.33, 29.57, 28.91, 27.27,26.06, 25.88, 25.57. HRMS(m / z) [ESI]: calculated for C 16 H 21 N2O2 + m / z [M+H] + :273.1598, found 273.1560.

[0166] Embodiment 17:

[0167] 3-(Cyclohexyl(hydroxy)methyl)-1-ethylquinoxaline-2(1 H Preparation and characterization of )-ketone (3fa):

[0168]

[0169] 3fa

[0170] 0.4 mmol of 1-ethylquinoxaline-2(1 H )-ketone, 2.4 mmol cyclohexylcarboxaldehyde, 0.6 mmol tetrabutylammonium perchlorate, and 0.08 mmol ferrocene were placed in a 10 mL three-necked round-bottom flask;

[0171] Then add 6.0 mL of N,N -dimethylformamide solvent dissolution, using a platinum sheet (1 cm x 1 cm) as the anode and a graphite rod (Φ 6 mm) as the cathode, stirring the reaction at 45 °C with a constant current of 15 mA until the substrate is completely consumed (monitored by thin layer chromatography, reaction time is 5 hours);

[0172] After the reaction was completed, the reaction solution was extracted with ethyl acetate and water, and the combined organic phase solution was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (300-400 mesh silica gel, petroleum ether / ethyl acetate = 30:1) to obtain the target product 3fa.

[0173] The product is characterized by:

[0174] white solid (83.6 mg, 73%). mp: 144 - 145℃. 1 H NMR (600 MHz, DMSO- d 6)δ7.85 - 7.84 (m, 1H), 7.63-7.62 (m, 2H), 7.39 - 7.37 (m, 1H), 4.83 (d, J = 6.8Hz, 1H), 4.72 (t, J = 6.5 Hz, 1H), 4.32 - 4.22 (m, 2H), 1.93 - 1.88 (m, 1H), 1.67 - 1.56 (m, 4H), 1.43 - 1.41 (m, 1H), 1.23 (t, J = 7.1 Hz, 3H), 1.18 -1.04 (m, 5H). 13 C NMR (150 MHz, DMSO- d6)δ 160.46, 153.10, 131.86, 131.77,130.41, 129.46, 123.44, 114.49, 73.01, 41.40, 36.73, 29.49, 27.38, 26.06,25.84, 25.56, 12.38. HRMS (m / z) [ESI]: calculated for C 17 H 23 N2O2 + m / z [M+H] + :287.1754, found 287.1753.

[0175] Embodiment 18:

[0176] 3-(Cyclohexyl(hydroxy)methyl)-1-isopropylquinoxaline-2(1 H Preparation and characterization of )-ketone (3ga):

[0177]

[0178] 3ga

[0179] 0.4 mmol of 1-isopropylquinoxaline-2-(1 H )-ketone, 2.4 mmol cyclohexylcarboxaldehyde, 0.6 mmol tetrabutylammonium perchlorate, and 0.08 mmol ferrocene were placed in a 10 mL three-necked round-bottom flask;

[0180] Then add 6.0 mL of N,N -dimethylformamide solvent dissolution, using a platinum sheet (1 cm x 1 cm) as the anode and a graphite rod (Φ 6 mm) as the cathode, stirring the reaction at 45 °C with a constant current of 15 mA until the substrate is completely consumed (monitored by thin layer chromatography, reaction time is 5 hours);

[0181] After the reaction was completed, the reaction solution was extracted with ethyl acetate and water, and the combined organic phase solution was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (300-400 mesh silica gel, petroleum ether / ethyl acetate = 30:1) to obtain the target product 3ga.

[0182] The product is characterized by:

[0183] yellow liquid (96.1 mg, 80%). 1 H NMR (600 MHz, DMSO- d 6)δ 7.96 (dd, J=8.2, 1.4 Hz, 1H), 7.78 (dd, J = 8.3, 1.4 Hz, 1H), 7.67 (ddd, J = 8.3, 7.0,1.5 Hz, 1H), 7.58 (ddd, J = 8.3, 6.9, 1.4 Hz, 1H), 5.49-5.43 (m, 1H), 5.01(d, J = 6.6 Hz, 1H), 4.71 (t, J = 6.8 Hz, 1H), 1.94 - 1.89 (m, 1H), 1.79 -1.75 (m,1H), 1.66 - 1.55 (m, 3H), 1.37 (t, J = 5.8, 6H), 1.28 - 1.25 (m, 1H), 1.13 - 1.05 (m, 5H). 13 C NMR (150 MHz, DMSO- d 6)δ 154.49, 152.06, 139.34,137.45, 129.62, 128.20, 126.54, 126.46, 72.73, 68.89, 42.44, 29.18, 28.09,26.04, 25.81, 25.56, 21.58, 21.51. HRMS(m / z) [ESI]: calculated for C 18 H 25 N2O2 + m / z [M+H] + : 301.1911, found 301.1911.

[0184] Embodiment 19:

[0185] 3-(Cyclohexyl(hydroxy)methyl)-1-allylquinoxaline-2(1 H Preparation and characterization of )-ketone (3HA):

[0186]

[0187] 3ha

[0188] 0.4 mmol 1-allylquinoxaline-2(1 H )-ketone, 2.4 mmol cyclohexylcarboxaldehyde, 0.6 mmol tetrabutylammonium perchlorate, and 0.08 mmol ferrocene were placed in a 10 mL three-necked round-bottom flask;

[0189] Then add 6.0 mL of N,N -dimethylformamide solvent dissolution, using a platinum sheet (1 cm x 1 cm) as the anode and a graphite rod (Φ 6 mm) as the cathode, stirring the reaction at 45 °C with a constant current of 15 mA until the substrate is completely consumed (monitored by thin layer chromatography, reaction time is 5 hours);

[0190] After the reaction was completed, the reaction solution was extracted with ethyl acetate and water, and the combined organic phase solution was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (300-400 mesh silica gel, petroleum ether / ethyl acetate = 30:1) to obtain the target product 3ha.

[0191] The product is characterized by:

[0192] white solid (82.3 mg, 69%). mp: 128 - 129℃. 1 H NMR (400 MHz, DMSO- d 6)δ7.85 (dd, J = 8.0, 1.4 Hz, 1H), 7.61-7.57 (m, 1H), 7.50 - 7.48 (m, 1H), 7.39- 7.35 (m, 1H), 5.98- 5.89 (m, 1H), 5.19 - 5.16 (m, 1H), 5.03 - 4.99 (m, 1H), 4.95 - 4.8 (m, 2H), 4.86 (d, J = 6.8 Hz, 1H), 4.72 (d, J = 6.5 Hz, 1H), 1.97- 1.85 (m, 1H), 1.68 - 1.56 (m, 4H), 1.44 - 1.42 (m, 1H), 1.21 - 1.07 (m,5H). 13 C NMR (100 MHz, DMSO- d 6)δ 160.58, 153.19, 133.14, 132.02, 131.75,131.56, 130.23, 129.30, 123.56, 116.99, 115.07, 73.08, 43.64, 41.44, 29.46,27.41, 26.05, 25.83, 25.56. HRMS(m / z) [ESI]: calculated for C 18H 23 N2O2 + m / z [M+H] + : 299.1754, found299.1751.

[0193] Embodiment 20:

[0194] 3-(Cyclohexyl(hydroxy)methyl)-1-benzylquinoxaline-2(1 H Preparation and characterization of )-ketone (3ia):

[0195]

[0196] 3ia

[0197] 0.4 mmol of 1-benzylquinoxaline-2(1 H )-ketone, 2.4 mmol cyclohexylcarboxaldehyde, 0.6 mmol tetrabutylammonium perchlorate, and 0.08 mmol ferrocene were placed in a 10 mL three-necked round-bottom flask;

[0198] Then add 6.0 mL of N,N -DIMFA solvent dissolution, using a platinum sheet (1 cm x 1 cm) as the anode and a graphite rod (Φ 6 mm) as the cathode, stirring the reaction at 45 °C with a constant current of 15 mA until the substrate is completely consumed (monitored by thin layer chromatography, 5 hours);

[0199] After the reaction was completed, the reaction solution was extracted with ethyl acetate and water, and the combined organic phase solution was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (300-400 mesh silica gel, petroleum ether / ethyl acetate = 30:1) to obtain the target product 3ia.

[0200] The product is characterized by:

[0201] white solid (100.4 mg, 72%). mp: 123 - 124℃. 1 H NMR (600 MHz, DMSO- d 6)δ 7.86 (dd, J = 8.0, 1.5 Hz, 1H), 7.53-7.50 (m, 1H), 7.45 (dd, J = 8.6, 1.2Hz, 1H), 7.36 - 7.33 (m, 1H), 7.31 (t, J = 7.5 Hz, 2H), 7.24 (t, J= 8.1 Hz,3H), 5.57 - 5.46 (m, 2H), 4.94 (d, J = 6.7 Hz, 1H), 4.79 (t, J = 6.4 Hz, 1H),1.96 (dd, J = 14.8, 7.1 Hz, 1H), 1.72 - 1.57 (m, 4H), 1.46 (d, J = 11.2 Hz,1H), 1.22 - 1.10 (m, 5H). 13 C NMR (150 MHz, DMSO- d 6)δ160.88, 153.84, 135.92,132.12, 131.96, 130.39, 129.50, 128.83, 127.48, 126.83, 123.80, 115.17,73.20, 44.76, 41.58, 29.56, 27.57, 26.13, 25.91, 25.64. HRMS(m / z) [ESI]:calculated for C 22 H 25 N2O2 + m / z [M+H] + : 349.1911, found 349.1914.

[0202] Embodiment 21:

[0203] 3-(Cyclohexyl(hydroxy)methyl)quinoxaline-2(1 H )-ketone (3aa) scale-up experimental preparation process:

[0204]

[0205] 3aa

[0206] A continuous flow electrochemical reactor was used with a platinum sheet (8 cm x 6 cm) as the anode and a graphite sheet (8 cm x 6 cm) as the cathode. 10 mmol of quinoxaline-2(1 H )-ketone, 60 mmol cyclohexylcarboxaldehyde, 15 mmol tetrabutylammonium perchlorate, and 2 mmol ferrocene were placed in a 250 mL flask;

[0207] Then add 150 mL of N,N-DIMETHYLFAMIDE was dissolved and mixed, and then transferred to a syringe. The syringe pump used had a flow rate of 0.20 mL / min and a constant current of 45 mA. The reaction was carried out at room temperature, and the outlet reaction solution was collected;

[0208] After the reaction was completed, the reaction solution was extracted with ethyl acetate and water, and the combined organic phase solution was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (300-400 mesh silica gel, petroleum ether / ethyl acetate = 30:1 elution) to obtain the target product 3aa (1.86 g, 72%).

[0209] The above examples demonstrate that under mild electrochemical conditions, quinoxaline-2(1 H Synthesis of 3-hydroxyalkylquinoxaline-2(1 H )-ketone compounds. This method avoids the use of stoichiometric oxidants and heavy metal catalysts, is environmentally friendly, and has high atom economy. Further scale-up studies using a continuous flow electrochemical reactor have shown that it is suitable for large-scale industrial production.

Claims

1. An electrochemical synthesis of 3-hydroxyalkylquinoxaline-2(1 H )-ketone compound, characterized in that The general synthesis formula of the compound is as follows: ， In the general formula, aldehyde is a fatty aldehyde; R 1 , R 2 = alkyl or halogen; The electrolyte is: tetrabutylammonium perchlorate, tetrabutylammonium tetrafluoroborate or tetrabutylammonium iodide; The solvent is: N , N -dimethylformamide or N , N - dimethylacetamide; The catalyst is: ferrocene or 2,2,6,6-tetramethylpiperidinyl oxide.

2. The electrochemical synthesis of 3-hydroxyalkylquinoxaline-2(1 H )-ketone compound, characterized in that: The synthesis method is: 0.4 mmol of quinoxaline-2(1 H )-ketone compound, 2.4 mmol of fatty aldehyde, 0.6 mmol of electrolyte, and 0.08 mmol of catalyst were added into a 10 mL three-necked round-bottom flask; Then, 6.0 mL of solvent was added to dissolve, and a platinum sheet was used as an anode and a graphite rod was used as a cathode. The reaction was stirred at 45 °C and a constant current of 15 mA was used. The reaction progress was monitored by thin layer chromatography. The reaction time was 5-6 hours until the substrate was completely consumed. After the reaction was completed, the reaction solution was extracted with ethyl acetate and water, the combined organic phase solution was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure, and the concentrate was purified by 300-400 mesh silica gel column chromatography to obtain the target product.

3. The electrochemical synthesis of 3-hydroxyalkylquinoxaline-2-(1 H )-ketone compound, characterized in that: The column chromatography purification uses petroleum ether / ethyl acetate as eluent, wherein the volume ratio of petroleum ether / ethyl acetate is 30:1.

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