A kind of 3-sulfone base coumarin and preparation method thereof

Abstract

The invention discloses a 3-sulfone-based coumarin and a preparation method thereof. The method of the invention is to react an aromatic amine, phenyl phenylpropiolate and serotonin in an organic solvent to prepare a 3-sulfone-based coumarin elemental compounds whose structures have been 1 H NMR, 13 Characterized and confirmed by C NMR, HRMS and other methods. The method of the present invention reacts under mild conditions, and utilizes diaoba block as a source of sulfur dioxide to directly realize the sulfonylation reaction and construct a 3-sulfone-based coumarin compound; the conversion reaction raw materials are simple and easy to obtain, and the traditional synthesis method is avoided The use of medium sulfonyl chloride is suitable for large-scale preparation and has very good application prospects.

Description

technical field

[0001] The invention belongs to the technical field of coumarin, and in particular relates to a 3-sulfone coumarin and a preparation method thereof. Background technique

[0002] Coumarin compounds play an important role in medicine, dyes, materials and other fields. The coumarin skeleton is one of the common heterocyclic structures, which widely exists in a variety of natural products and drug molecules with significant biological activities. For example, Calanolide A extracted from the plant Populus euphratica exhibits very good HIV-1 reverse transcriptase inhibitory activity and is a potential anti-AIDS drug; the coumarin compound warfarin (Wafarin) is a widely used It is an anticoagulant used in clinical medicine; umbelliferide in rue, escin in chinensis and angelica lactone in lovage all have a coumarin skeleton; industrialized coumarin fluorescent dyes include disperse yellow 184, Disperse Yellow 232, Solvent Red 196 and Disperse Red 277, etc. Its de...

Examples

Embodiment 1

[0020] A kind of 3-sulfone base coumarin, structural formula is:

[0021] The preparation method is as follows: add 1.5 equivalents of arylamine, 1.5 mL of 1,2-dichloroethane, 1.8 equivalents of tBuONO, and 1.5 equivalents of boron trifluoride ether solution in the reaction tube, under the protection of inert gas nitrogen or argon, Stir at 0°C for 10 minutes; then add 0.2mmol of phenylpropiolate, 1.6 equivalents of chloroform, and 2.0mL of 1,2-dichloroethane, stir at 70-80°C for 5.0-6.0 hours, until the TLC detection is complete reaction. After the reaction solution was washed with water, it was extracted with ethyl acetate, and the extract was concentrated and then separated by column chromatography to obtain the corresponding 3-sulfone coumarin Ia with a reaction yield of 83%.

[0022] The structure of the compound has been 1 H NMR, 13 Characterized and confirmed by C NMR, HRMS and other methods: 1 H NMR (400MHz, CDCl 3 )δ7.95(d,J=8.9Hz,2H),7.56-7.58(m,3H),7.32-7.34(m...

Embodiment 2

[0024] A kind of 3-sulfone group coumarin, structural formula is

[0025] The preparation method is: sequentially add arylamine (1.5 equivalents), 1,2-dichloroethane (1.5 mL), tBuONO (1.8 equivalents), boron trifluoride ether solution (1.5 equivalents) in a reaction tube, and inert gas Under the protection of nitrogen or argon, stir at 0°C for 10 minutes; then add phenylpropiolate (0.2mmol), chloroform (1.6eq) and 1,2-dichloroethane (2.0mL), at 70 Stir at ~80°C for 5.0-6.0 hours until the reaction is complete as detected by TLC. After the reaction solution was washed with water, it was extracted with ethyl acetate, and the extract was concentrated and then separated by column chromatography to obtain the corresponding 3-sulfone coumarin Ib with a reaction yield of 84.5%.

[0026] The structure of the compound has been 1 H NMR, 13 Characterized and confirmed by C NMR, HRMS and other methods: 1 H NMR (400MHz, CDCl 3 )δ7.94(d, J=8.6Hz, 2H), 7.58-7.89(m, 3H), 7.47(d, J=8.6H...

Embodiment 3

[0028] A kind of 3-sulfone group coumarin, structural formula is

[0029]The preparation method is: sequentially add arylamine (1.5 equivalents), 1,2-dichloroethane (1.5 mL), tBuONO (1.8 equivalents), boron trifluoride ether solution (1.5 equivalents) in a reaction tube, and inert gas Under the protection of nitrogen or argon, stir at 0°C for 10 minutes; then add phenylpropiolate (0.2mmol), chloroform (1.6eq) and 1,2-dichloroethane (2.0mL), Stir at ~80°C for 5.0-6.0 hours until the reaction is complete as detected by TLC. After the reaction solution was washed with water, it was extracted with ethyl acetate, and the extract was concentrated and then separated by column chromatography to obtain the corresponding 3-sulfone coumarin Ic with a reaction yield of 85%.

[0030] The structure of the compound has been 1 H NMR, 13 Characterized and confirmed by C NMR, HRMS and other methods: 1 H NMR (400MHz, CDCl 3 )δ7.87(d,J=8.7Hz,2H),7.64(d,J=8.7Hz,2H),7.58-7.59(m,3H),7.32-7.34...

technical field

[0001] The invention belongs to the technical field of coumarin, and in particular relates to a 3-sulfone coumarin and a preparation method thereof. Background technique

[0002] Coumarin compounds play an important role in medicine, dyes, materials and other fields. The coumarin skeleton is one of the common heterocyclic structures, which widely exists in a variety of natural products and drug molecules with significant biological activities. For example, Calanolide A extracted from the plant Populus euphratica exhibits very good HIV-1 reverse transcriptase inhibitory activity and is a potential anti-AIDS drug; the coumarin compound warfarin (Wafarin) is a widely used It is an anticoagulant used in clinical medicine; umbelliferide in rue, escin in chinensis and angelica lactone in lovage all have a coumarin skeleton; industrialized coumarin fluorescent dyes include disperse yellow 184, Disperse Yellow 232, Solvent Red 196 and Disperse Red 277, etc. Its de...

Examples

Embodiment 1

[0020] A kind of 3-sulfone base coumarin, structural formula is:

[0021] The preparation method is as follows: add 1.5 equivalents of arylamine, 1.5 mL of 1,2-dichloroethane, 1.8 equivalents of tBuONO, and 1.5 equivalents of boron trifluoride ether solution in the reaction tube, under the protection of inert gas nitrogen or argon, Stir at 0°C for 10 minutes; then add 0.2mmol of phenylpropiolate, 1.6 equivalents of chloroform, and 2.0mL of 1,2-dichloroethane, stir at 70-80°C for 5.0-6.0 hours, until the TLC detection is complete reaction. After the reaction solution was washed with water, it was extracted with ethyl acetate, and the extract was concentrated and then separated by column chromatography to obtain the corresponding 3-sulfone coumarin Ia with a reaction yield of 83%.

[0022] The structure of the compound has been 1 H NMR, 13 Characterized and confirmed by C NMR, HRMS and other methods: 1 H NMR (400MHz, CDCl 3 )δ7.95(d,J=8.9Hz,2H),7.56-7.58(m,3H),7.32-7.34(m...

Embodiment 2

[0024] A kind of 3-sulfone group coumarin, structural formula is

[0025] The preparation method is: sequentially add arylamine (1.5 equivalents), 1,2-dichloroethane (1.5 mL), tBuONO (1.8 equivalents), boron trifluoride ether solution (1.5 equivalents) in a reaction tube, and inert gas Under the protection of nitrogen or argon, stir at 0°C for 10 minutes; then add phenylpropiolate (0.2mmol), chloroform (1.6eq) and 1,2-dichloroethane (2.0mL), at 70 Stir at ~80°C for 5.0-6.0 hours until the reaction is complete as detected by TLC. After the reaction solution was washed with water, it was extracted with ethyl acetate, and the extract was concentrated and then separated by column chromatography to obtain the corresponding 3-sulfone coumarin Ib with a reaction yield of 84.5%.

[0026] The structure of the compound has been 1 H NMR, 13 Characterized and confirmed by C NMR, HRMS and other methods: 1 H NMR (400MHz, CDCl 3 )δ7.94(d, J=8.6Hz, 2H), 7.58-7.89(m, 3H), 7.47(d, J=8.6H...

Embodiment 3

[0028] A kind of 3-sulfone group coumarin, structural formula is

[0029]The preparation method is: sequentially add arylamine (1.5 equivalents), 1,2-dichloroethane (1.5 mL), tBuONO (1.8 equivalents), boron trifluoride ether solution (1.5 equivalents) in a reaction tube, and inert gas Under the protection of nitrogen or argon, stir at 0°C for 10 minutes; then add phenylpropiolate (0.2mmol), chloroform (1.6eq) and 1,2-dichloroethane (2.0mL), Stir at ~80°C for 5.0-6.0 hours until the reaction is complete as detected by TLC. After the reaction solution was washed with water, it was extracted with ethyl acetate, and the extract was concentrated and then separated by column chromatography to obtain the corresponding 3-sulfone coumarin Ic with a reaction yield of 85%.

[0030] The structure of the compound has been 1 H NMR, 13 Characterized and confirmed by C NMR, HRMS and other methods: 1 H NMR (400MHz, CDCl 3 )δ7.87(d,J=8.7Hz,2H),7.64(d,J=8.7Hz,2H),7.58-7.59(m,3H),7.32-7.34...

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