Method for synthesizing furan [3,2-c] coumarin derivatives

Abstract

The invention discloses a method for synthesizing furan [3,2-c] coumarin derivatives. The method comprises the following step: reacting 2,3-dichloro-5,6-dicyano-1,4-benzoquinone serving as a butylene dinitrile block with a 4-hydroxycoumarin analogue in a dried organic solvent at room temperature for several hours, thereby obtaining the target. According to the method, the defects that the raw materials need to be pre-functionalized or expensive metal catalysts are needed in the prior art are overcome. The synthesis method disclosed by the invention is of significance in the research field of furan [3,2-c] coumarin derivatives.

Description

technical field

[0001] The present invention relates to a preparation method of furo[3,2-c]coumarin derivatives, in particular to a preparation method of 4-hydroxycoumarin compounds and 2,3-dichloro-5,6- A method for preparing furo[3,2-c]coumarin derivatives by reacting dicyano-1,4-benzoquinone. Background technique

[0002] The coumarin nucleus is a class of dominant heterocyclic structures, which widely exist in many natural products, medicines and compounds with biological activity. Meanwhile, coumarin derivatives are also widely used as protein labeling probes and functional dyes. Furo[3,2-c]coumarin is a kind of furocoumarin, which has attracted extensive attention because of its potential biological and pharmacological activities. It is a class of very potential drug target molecules and lead structures. For example, natural Neo-tanshinlactione and its analogues have been found to have strong selective anti-breast cancer effects. Therefore, the preparation of furo[3...

Examples

Embodiment 1

[0021] Embodiment 1, use 4-hydroxycoumarin and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone to synthesize furan [3,2- c ] coumarin, and detect the effect of different solvents on the oxidative cyclization reaction (shown in the formula II-1 compound as an example)

[0022] In the reaction flask, successively add 2,3-dichloro-5,6-dicyano-1,4-p-benzoquinone (1.5 mmol), 4-hydroxycoumarin (0.5 mmol) and different reaction solvents (2 mL) (nitromethane, acetonitrile, ethyl acetate, 1,2-dichloroethane, dichloromethane), react at room temperature for 8 h. The solid was dissolved with ethyl acetate to obtain a clear solution, which was washed with saturated aqueous sodium bicarbonate until the aqueous solution was essentially colorless. The organic phase was evaporated to dryness, and the target product was isolated by silica gel column chromatography or (and) recrystallization, and the calculated separation yield was shown in Table 1, wherein the target product in acetonitrile II-1...

Embodiment 2

[0026] Embodiment 2, shown in the formula II-2 compound synthesis

[0027] The 4-hydroxycoumarin in Example 1 was replaced by 4-hydroxy-6-methylcoumarin, and the other reaction conditions were the same as in Example 1, and the yield was 85%.

[0028]

[0029] Mp 252-254 o C; 1 H NMR (400 MHz, DMSO- d 6 ): δ 7.94 (d, J = 1.1 Hz, 1H), 7.66 (dd, J = 8.6, 2.0 Hz, 1H), 7.57 (d, J = 8.6 Hz, 1H), 2.45 (s, 3H); 13 C NMR (101 MHz, DMSO- d 6 ): δ 160.1 , 154.8 , 152.1 , 136.1 , 135.8 , 133.0 , 122.2 , 117.9 , 110.6 , 109.8 , 109.2 , 109.2 , 106.7 , 20.7 ; -1

Embodiment 3

[0030] Embodiment 3, shown in the formula II-3 compound synthesis

[0031] The 4-hydroxycoumarin in Example 1 was replaced by 4-hydroxy-7-methylcoumarin, and the other reaction conditions were the same as in Example 1, and the yield was 86%.

[0032]

[0033] Mp 261-262 o C; 1 H NMR (400 MHz, DMSO- d 6 ): δ 8.02 (d, J = 8.0 Hz, 1H), 7.52 (s, 1H), 7.40 (d, J = 8.0 Hz, 1H), 2.49 (s, 1H); 13 C NMR (101 MHz, DMSO- d 6 ): δ 160.4, 154.8, 154.0, 146.4, 132.8, 127.4, 122.5, 118.0, 109.2, 109.1, 109.0, 108.4, 106.7, 22.0; IR (KBr): ν 2248, 2238, cm 175 -1

technical field

[0001] The present invention relates to a preparation method of furo[3,2-c]coumarin derivatives, in particular to a preparation method of 4-hydroxycoumarin compounds and 2,3-dichloro-5,6- A method for preparing furo[3,2-c]coumarin derivatives by reacting dicyano-1,4-benzoquinone. Background technique

[0002] The coumarin nucleus is a class of dominant heterocyclic structures, which widely exist in many natural products, medicines and compounds with biological activity. Meanwhile, coumarin derivatives are also widely used as protein labeling probes and functional dyes. Furo[3,2-c]coumarin is a kind of furocoumarin, which has attracted extensive attention because of its potential biological and pharmacological activities. It is a class of very potential drug target molecules and lead structures. For example, natural Neo-tanshinlactione and its analogues have been found to have strong selective anti-breast cancer effects. Therefore, the preparation of furo[3...

Examples

Embodiment 1

[0021] Embodiment 1, use 4-hydroxycoumarin and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone to synthesize furan [3,2- c ] coumarin, and detect the effect of different solvents on the oxidative cyclization reaction (shown in the formula II-1 compound as an example)

[0022] In the reaction flask, successively add 2,3-dichloro-5,6-dicyano-1,4-p-benzoquinone (1.5 mmol), 4-hydroxycoumarin (0.5 mmol) and different reaction solvents (2 mL) (nitromethane, acetonitrile, ethyl acetate, 1,2-dichloroethane, dichloromethane), react at room temperature for 8 h. The solid was dissolved with ethyl acetate to obtain a clear solution, which was washed with saturated aqueous sodium bicarbonate until the aqueous solution was essentially colorless. The organic phase was evaporated to dryness, and the target product was isolated by silica gel column chromatography or (and) recrystallization, and the calculated separation yield was shown in Table 1, wherein the target product in acetonitrile II-1...

Embodiment 2

[0026] Embodiment 2, shown in the formula II-2 compound synthesis

[0027] The 4-hydroxycoumarin in Example 1 was replaced by 4-hydroxy-6-methylcoumarin, and the other reaction conditions were the same as in Example 1, and the yield was 85%.

[0028]

[0029] Mp 252-254 o C; 1 H NMR (400 MHz, DMSO- d 6 ): δ 7.94 (d, J = 1.1 Hz, 1H), 7.66 (dd, J = 8.6, 2.0 Hz, 1H), 7.57 (d, J = 8.6 Hz, 1H), 2.45 (s, 3H); 13 C NMR (101 MHz, DMSO- d 6 ): δ 160.1 , 154.8 , 152.1 , 136.1 , 135.8 , 133.0 , 122.2 , 117.9 , 110.6 , 109.8 , 109.2 , 109.2 , 106.7 , 20.7 ; -1

Embodiment 3

[0030] Embodiment 3, shown in the formula II-3 compound synthesis

[0031] The 4-hydroxycoumarin in Example 1 was replaced by 4-hydroxy-7-methylcoumarin, and the other reaction conditions were the same as in Example 1, and the yield was 86%.

[0032]

[0033] Mp 261-262 o C; 1 H NMR (400 MHz, DMSO- d 6 ): δ 8.02 (d, J = 8.0 Hz, 1H), 7.52 (s, 1H), 7.40 (d, J = 8.0 Hz, 1H), 2.49 (s, 1H); 13 C NMR (101 MHz, DMSO- d 6 ): δ 160.4, 154.8, 154.0, 146.4, 132.8, 127.4, 122.5, 118.0, 109.2, 109.1, 109.0, 108.4, 106.7, 22.0; IR (KBr): ν 2248, 2238, cm 175 -1