Method for preparing N-(2-formyl phenyl) N-substituted formamide derivatives by means of visible light catalysis

Abstract

The invention relates to a method for preparing N-(2-formyl phenyl) N-substituted formamide derivatives by means of visible light catalysis, belonging to the technical field of visible light catalytic synthesis. A synthetic route is described in the description, wherein the structural formula of DPZ is described in the description, R<1> is -H, -OMe, -F or -Cl, and R<2> is -Me, -Bn or -Ph; the synthetic process comprises the steps of dissolving a compound 1, the DPZ, K3PO4 and TEMPO into a mixed solvent of CH3CN and water, carrying out a reaction at the constant temperature of 25 DEG C under a blue lamp light source in an oxygen atmosphere, tracking and monitoring by using thin layer chromatography (TLC), and after the reaction is finished, carrying out column chromatographic separation to obtain a compound 2. The method can be used for efficiently preparing the N-(2-formyl phenyl) N-substituted formamide derivatives, and has the advantages of being environmental-friendly, high in reaction efficiency, simple in aftertreatment and low in cost.

Description

technical field

[0001] The invention belongs to the technical field of visible light catalytic synthesis, and in particular relates to a method for preparing N-(2-formylphenyl) N-substituted formamide derivatives by visible light catalysis. Background technique

[0002] N-methylformamide compound is an important raw material for organic synthesis, and it is also a key intermediate for the synthesis of many biologically active compounds. Production of pharmaceuticals, synthetic leather, artificial leather, etc.

[0003] N-phenyl-N-substituted carboxamides are key steps in the synthesis of many natural products and drugs. N-(2-formylphenyl)-N-methylformamide is hydrolyzed under the action of NaOH to generate 2-methylaminobenzaldehyde, and 2-methylaminobenzaldehyde reacts with indole to obtain a new antimalarial drug Phyllophylline. N-(2-formylphenyl)-N-methylformamide generates amino-protected alcohol compounds through hydrolysis and reduction process, and removes benzyl gr...

Examples

Embodiment 1

[0021] The structural formula of compound 2a is as follows:

[0022]

[0023] The synthetic route of compound 2a is as follows:

[0024]

[0025] The synthetic steps of compound 2a are as follows:

[0026] (1) Add 28 μL (0.0005 mmol, 0.005 equiv) of DPZ solution (1 mg dissolved in 160 μl acetonitrile) into a 10 mL reaction flask, and then remove the solvent by rotary evaporation;

[0027] (2) Then add magneton, N-methylindole 1a (0.1mmol, 1.0equiv), solvent (2.0mL, CH 3 CN:H 2 O volume ratio=10:1), K 3 PO 4 (0.3mmol, 3equiv.) and 10equiv% TEMPO (0.01mmol) as additives, seal the reaction bottle, and insert an oxygen bulb on the bottle stopper to provide oxygen to the reaction bottle;

[0028] (3) Put the reaction bottle into a 25°C incubator, and stir the reaction at a distance of 5cm from a 3W blue light (λ=450-455nm); (4) The reaction is detected by a TLC plate. After the reaction is complete, extract with ethyl acetate , spin-dried, passed through the column (col...

Embodiment 2

[0031]

[0032] Product Name: N-(2-Formylphenyl)-N-Benzylformamide

[0033] In step (2), N-methylindole 1a was replaced with p-N-benzylindole 1b, and other preparation steps and purification methods were carried out with reference to Example 1; yellow oil, 96% yield. 1 H NMR (300MHz, CDCl 3 )δ9.77 (s, 1H), 8.64 and 8.27 (s, 1H, CHO rotameric), 7.92–7.87 (m, 1H), 7.64–7.55 (m, 1H), 7.43–7.51 (m, J=11.3, 7.5,1H), 7.31–7.28(m,1H), 7.25–7.03(m,5H), 4.98 and 4.83(s,2H,CH 2 rotameric). 13 C NMR (75MHz, CDCl 3 )δ189.2, 189.0, 162.8, 162.3, 142.0, 139.9, 135.3, 135.2, 134.9, 132.8, 132.3, 130.4, 129.2, 129.1, 129.0, 128.8, 128.6, 128.6, 128.5, 128.2 HR, 58.2 m / z 240.1032(M+H + ), calc.for C 15 h 14 NO 2 240.1025.

Embodiment 3

[0035]

[0036] Product name: N-(2-formylphenyl)-N-phenylcarboxamide

[0037] In step (2), p-N-phenylindole 1 was used to replace N-methylindole 1a, and other preparation steps and purification methods were carried out with reference to Example 1; yellow oil, 85% yield. 1HNMR (300MHz, CDCl3) δ10.14 and 10.07 (s, 1H, CHOrotameric), 8.84 and 8.54 (s, 1H, CHO rotameric), 8.01 (dd, J = 7.7, 1.6, 1H), 7.73-7.65 (m, 1H),7.60–7.48(m,1H),7.43–7.27(m,4H),7.25–7.13(m,2H).13C NMR(75MHz,CDCl3)δ189.0,188.9,162.3,161.6,141.6,140.4,135.4 ,135.1,132.2,130.6,130.2,129.9,129.7,129.3,128.9,128.7,126.9,126.6,124.5,123.4.HRMS(ESI)m / z 226.0873(M+H + ), calc.for C 14 h 12 NO 2 226.0868.

technical field

[0001] The invention belongs to the technical field of visible light catalytic synthesis, and in particular relates to a method for preparing N-(2-formylphenyl) N-substituted formamide derivatives by visible light catalysis. Background technique

[0002] N-methylformamide compound is an important raw material for organic synthesis, and it is also a key intermediate for the synthesis of many biologically active compounds. Production of pharmaceuticals, synthetic leather, artificial leather, etc.

[0003] N-phenyl-N-substituted carboxamides are key steps in the synthesis of many natural products and drugs. N-(2-formylphenyl)-N-methylformamide is hydrolyzed under the action of NaOH to generate 2-methylaminobenzaldehyde, and 2-methylaminobenzaldehyde reacts with indole to obtain a new antimalarial drug Phyllophylline. N-(2-formylphenyl)-N-methylformamide generates amino-protected alcohol compounds through hydrolysis and reduction process, and removes benzyl gr...

Examples

Embodiment 1

[0021] The structural formula of compound 2a is as follows:

[0022]

[0023] The synthetic route of compound 2a is as follows:

[0024]

[0025] The synthetic steps of compound 2a are as follows:

[0026] (1) Add 28 μL (0.0005 mmol, 0.005 equiv) of DPZ solution (1 mg dissolved in 160 μl acetonitrile) into a 10 mL reaction flask, and then remove the solvent by rotary evaporation;

[0027] (2) Then add magneton, N-methylindole 1a (0.1mmol, 1.0equiv), solvent (2.0mL, CH 3 CN:H 2 O volume ratio=10:1), K 3 PO 4 (0.3mmol, 3equiv.) and 10equiv% TEMPO (0.01mmol) as additives, seal the reaction bottle, and insert an oxygen bulb on the bottle stopper to provide oxygen to the reaction bottle;

[0028] (3) Put the reaction bottle into a 25°C incubator, and stir the reaction at a distance of 5cm from a 3W blue light (λ=450-455nm); (4) The reaction is detected by a TLC plate. After the reaction is complete, extract with ethyl acetate , spin-dried, passed through the column (col...

Embodiment 2

[0031]

[0032] Product Name: N-(2-Formylphenyl)-N-Benzylformamide

[0033] In step (2), N-methylindole 1a was replaced with p-N-benzylindole 1b, and other preparation steps and purification methods were carried out with reference to Example 1; yellow oil, 96% yield. 1 H NMR (300MHz, CDCl 3 )δ9.77 (s, 1H), 8.64 and 8.27 (s, 1H, CHO rotameric), 7.92–7.87 (m, 1H), 7.64–7.55 (m, 1H), 7.43–7.51 (m, J=11.3, 7.5,1H), 7.31–7.28(m,1H), 7.25–7.03(m,5H), 4.98 and 4.83(s,2H,CH 2 rotameric). 13 C NMR (75MHz, CDCl 3 )δ189.2, 189.0, 162.8, 162.3, 142.0, 139.9, 135.3, 135.2, 134.9, 132.8, 132.3, 130.4, 129.2, 129.1, 129.0, 128.8, 128.6, 128.6, 128.5, 128.2 HR, 58.2 m / z 240.1032(M+H + ), calc.for C 15 h 14 NO 2 240.1025.

Embodiment 3

[0035]

[0036] Product name: N-(2-formylphenyl)-N-phenylcarboxamide

[0037] In step (2), p-N-phenylindole 1 was used to replace N-methylindole 1a, and other preparation steps and purification methods were carried out with reference to Example 1; yellow oil, 85% yield. 1HNMR (300MHz, CDCl3) δ10.14 and 10.07 (s, 1H, CHOrotameric), 8.84 and 8.54 (s, 1H, CHO rotameric), 8.01 (dd, J = 7.7, 1.6, 1H), 7.73-7.65 (m, 1H),7.60–7.48(m,1H),7.43–7.27(m,4H),7.25–7.13(m,2H).13C NMR(75MHz,CDCl3)δ189.0,188.9,162.3,161.6,141.6,140.4,135.4 ,135.1,132.2,130.6,130.2,129.9,129.7,129.3,128.9,128.7,126.9,126.6,124.5,123.4.HRMS(ESI)m / z 226.0873(M+H + ), calc.for C 14 h 12 NO 2 226.0868.

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