Chemical synthesis method for substituting alpha, beta unsaturated ketone by sulphonyl

Abstract

The invention discloses a chemical synthesizing method of alpha, beta-unsaturated ketone substituted by sulfonyl as formula (I), which comprises the following steps: adding unsaturated ketone as formula (III) and 2,4,4,6-tetrabromine-2, 5-cyclohexadiene-1-ketone as bromide agent as formula (II); disposing to obtain the rough product of bromide; proceeding nucleophilic reaction for rough bromide product and RSO2Na as formula (IV); making R and R1 in the formula (I) as alkyl or aryl with random carbon number; setting the molar rate of unsaturated ketone and bromide agent at 1:1-2; setting the bulk rate of each molar of unsaturated ketone and aprotic polar solvent at 1:5-50; obtaining the density of inorganic acid in the aprotic solvent at 0. 1%-5%(g / ml).

Description

(1) Technical field

[0001] The invention relates to a chemical synthesis method for sulfonyl-substituted α, β unsaturated ketones. (2) Background technology

[0002] Sulfonyl-substituted α, β unsaturated ketones are a kind of prochiral bidentate coordination substrates in the Diels-Alder reaction, and can be used as dienophiles in the asymmetric catalytic Diels-Alder reaction we studied. In the Hetero Diels-Alder reaction, it can be used as a diene, and in the Michael reaction, it can be used as both an acceptor and a donor. The reported research results have proved that in the above reaction, as a new type of reaction substrate, it can be effectively matched with the chiral catalyst to achieve the ideal stereo control effect, and a chiral compound with high enantioselectivity has been synthesized. It has broad application prospects in the synthesis of chiral drugs and natural products.

[0003] Two methods have been reported for the synthesis of sulfonyl-substituted α, β-...

Examples

Embodiment 1

[0028] Example 1: Preparation of 4-phenyl-1-benzenesulfonyl-3-butene-2-one

[0029]

[0030] In a 500ml three-necked flask equipped with a mechanical stirring device, add 1.0 g (6.8 mmol) of 4-phenyl-3-buten-2-one, 2,4,4,6-tetrabromo-2,5-cyclohexyl 2.8 g (6.8 mmol) of dien-1-one was then added to 100 ml of 1,4-dioxane dissolved in 1% (g / ml) HCl, and stirred at room temperature for 2 hours. Stop the reaction and saturate with NaHCO 3 Neutralize, CH 2 Cl 2 It was extracted and dried, concentrated, dissolved in 100ml of ethanol, reacted with sodium benzenesulfinate dihydrate, post-treated, and recrystallized from ethanol to obtain 1.15g of the product with a yield of 65%, m.p.96-98°C. 1 H-NMR (CDCl 3 ): δ7.86-7.90 (m, 2H), 7.42-7.67 (m, 9H), 6.94 (1H, d, J=15.8Hz), 4.40 (s, 2H); MS (70ev) m / z: 286 (M + , 7).

Embodiment 2

[0031] Example 2: 4-p-methoxyphenyl-1-benzenesulfonyl-3-buten-2-one

[0032]

[0033] In a 500ml three-necked flask equipped with a mechanical stirring device, add 1.2 g (6.8 mmol) of 4-p-methoxyphenyl-3-buten-2-one, 2,4,4,6-tetrabromo-2, 5.6 g (13.6 mmol) of 5-cyclohexadien-1-one was added, and then 100 ml of acetonitrile dissolved in 5% (g / ml) HCl was added, and stirred at 60° C. for 5 hours. Stop the reaction and saturate with NaHCO 3 Neutralize, CH 2 Cl 2 It was extracted and dried, concentrated, dissolved in 100ml of ethanol, reacted with sodium benzenesulfinate dihydrate, post-treated, and recrystallized from ethanol to obtain 1.7g of the product with a yield of 78%, m.p.142-144°C. 1 H-NMR (CDCl 3 ): δ7.90-7.92(m, 2H), 7.52-7.67(m, 6H), 6.92-6.94(d, J=8.8Hz, 2H), 6.79-6.83(d, J=15.7Hz, 1H), 4.37(s, 2H), 3.86(s, 3H); MS(70ev) m / z(rel.intensity,%) 316(M + ,twenty four).

Embodiment 3

[0034] Example 3: 4-(4'-N, N-dimethylamino)phenyl-1-benzenesulfonyl-3-butene-2-one

[0035]

[0036]In a 500ml three-necked flask equipped with a mechanical stirring device, add 1.3g (6.8mmol) of 4-p-dimethylaminophenyl-3-buten-2-one, 2,4,4,6-tetrabromo-2 , 2.8g (6.8mmol) of 5-cyclohexadien-1-one, and then add 100ml of 1,4-dioxane dissolved in 0.1% (g / ml) HBr, and stir at 100°C for 1 hour. Stop the reaction and saturate with NaHCO 3 Neutralize, CH 2 Cl 2 It was extracted and dried, concentrated, dissolved in 100ml of ethanol, reacted with sodium benzenesulfinate dihydrate, post-treated, and recrystallized from ethanol to obtain 1.0 g of the product with a yield of 54%, m.p.157-159°C. 1 H-NMR (CDCl 3 ): δ7.92-7.90 (m, 2H), 7.44-7.65 (m, 6H), 6.69-6.67 (m, 3H), 4.35 (s, 2H), 3.06 (s, 3H).

(1) Technical field

[0001] The invention relates to a chemical synthesis method for sulfonyl-substituted α, β unsaturated ketones. (2) Background technology

[0002] Sulfonyl-substituted α, β unsaturated ketones are a kind of prochiral bidentate coordination substrates in the Diels-Alder reaction, and can be used as dienophiles in the asymmetric catalytic Diels-Alder reaction we studied. In the Hetero Diels-Alder reaction, it can be used as a diene, and in the Michael reaction, it can be used as both an acceptor and a donor. The reported research results have proved that in the above reaction, as a new type of reaction substrate, it can be effectively matched with the chiral catalyst to achieve the ideal stereo control effect, and a chiral compound with high enantioselectivity has been synthesized. It has broad application prospects in the synthesis of chiral drugs and natural products.

[0003] Two methods have been reported for the synthesis of sulfonyl-substituted α, β-...

Examples

Embodiment 1

[0028] Example 1: Preparation of 4-phenyl-1-benzenesulfonyl-3-butene-2-one

[0029]

[0030] In a 500ml three-necked flask equipped with a mechanical stirring device, add 1.0 g (6.8 mmol) of 4-phenyl-3-buten-2-one, 2,4,4,6-tetrabromo-2,5-cyclohexyl 2.8 g (6.8 mmol) of dien-1-one was then added to 100 ml of 1,4-dioxane dissolved in 1% (g / ml) HCl, and stirred at room temperature for 2 hours. Stop the reaction and saturate with NaHCO 3 Neutralize, CH 2 Cl 2 It was extracted and dried, concentrated, dissolved in 100ml of ethanol, reacted with sodium benzenesulfinate dihydrate, post-treated, and recrystallized from ethanol to obtain 1.15g of the product with a yield of 65%, m.p.96-98°C. 1 H-NMR (CDCl 3 ): δ7.86-7.90 (m, 2H), 7.42-7.67 (m, 9H), 6.94 (1H, d, J=15.8Hz), 4.40 (s, 2H); MS (70ev) m / z: 286 (M + , 7).

Embodiment 2

[0031] Example 2: 4-p-methoxyphenyl-1-benzenesulfonyl-3-buten-2-one

[0032]

[0033] In a 500ml three-necked flask equipped with a mechanical stirring device, add 1.2 g (6.8 mmol) of 4-p-methoxyphenyl-3-buten-2-one, 2,4,4,6-tetrabromo-2, 5.6 g (13.6 mmol) of 5-cyclohexadien-1-one was added, and then 100 ml of acetonitrile dissolved in 5% (g / ml) HCl was added, and stirred at 60° C. for 5 hours. Stop the reaction and saturate with NaHCO 3 Neutralize, CH 2 Cl 2 It was extracted and dried, concentrated, dissolved in 100ml of ethanol, reacted with sodium benzenesulfinate dihydrate, post-treated, and recrystallized from ethanol to obtain 1.7g of the product with a yield of 78%, m.p.142-144°C. 1 H-NMR (CDCl 3 ): δ7.90-7.92(m, 2H), 7.52-7.67(m, 6H), 6.92-6.94(d, J=8.8Hz, 2H), 6.79-6.83(d, J=15.7Hz, 1H), 4.37(s, 2H), 3.86(s, 3H); MS(70ev) m / z(rel.intensity,%) 316(M + ,twenty four).

Embodiment 3

[0034] Example 3: 4-(4'-N, N-dimethylamino)phenyl-1-benzenesulfonyl-3-butene-2-one

[0035]

[0036]In a 500ml three-necked flask equipped with a mechanical stirring device, add 1.3g (6.8mmol) of 4-p-dimethylaminophenyl-3-buten-2-one, 2,4,4,6-tetrabromo-2 , 2.8g (6.8mmol) of 5-cyclohexadien-1-one, and then add 100ml of 1,4-dioxane dissolved in 0.1% (g / ml) HBr, and stir at 100°C for 1 hour. Stop the reaction and saturate with NaHCO 3 Neutralize, CH 2 Cl 2 It was extracted and dried, concentrated, dissolved in 100ml of ethanol, reacted with sodium benzenesulfinate dihydrate, post-treated, and recrystallized from ethanol to obtain 1.0 g of the product with a yield of 54%, m.p.157-159°C. 1 H-NMR (CDCl 3 ): δ7.92-7.90 (m, 2H), 7.44-7.65 (m, 6H), 6.69-6.67 (m, 3H), 4.35 (s, 2H), 3.06 (s, 3H).

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