A method for preparing a dihydrocoumarin compound

Abstract

The present invention discloses a preparation method of dihydrocoumarin compounds, comprising the following steps: (1) sequentially adding raw material I, a photocatalyst, an auxiliary agent and a solvent into a reaction flask; (2) after the reaction system is stirred evenly, reacting at 40-60 °C for 12-48 h under light irradiation conditions; (3) after the reaction is completed, washing with dichloromethane and saturated NaCl solution, extracting and separating to obtain an organic phase and drying with anhydrous Na 2 SO 4 drying, evaporating the solvent under reduced pressure, and purifying by silica gel column chromatography to obtain the corresponding dihydrocoumarin compound II. In this application, substituted dihydrobenzopyran is used as a raw material, and a photocatalytic oxidation reaction occurs under light irradiation conditions to prepare dihydrocoumarin compounds. The reaction process of the present invention is simple, without the use of an oxidant, the reaction conversion rate is high, and the post-treatment is simple and easy to operate.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and particularly relates to a method for preparing dihydrocoumarin compounds. Background Art

[0002] Dihydrocoumarin has a sweet and mellow grassy aroma, accompanied by the aroma of licorice, cinnamon, and caramel; it can be used as a substitute for coumarin, mainly used in tobacco flavors, food flavors, and other various flavors, and is an important type of spice and fine chemical.

[0003] Currently, the main methods for synthesizing dihydrocoumarin are as follows: (1) Using coumarin as a raw material, hydrogenating it at 160 - 200 °C and under pressure in the presence of a nickel catalyst; (2) Using o-chlorophenylpropionic acid as a raw material, hydrolyzing it in an alkaline aqueous solution to form o-hydroxybenzene propionic acid, dehydrating, and then cyclizing; (3) Using o-toluidine as a raw material, hydrolyzing it in a hydrochloric acid aqueous solution to form o-chlorotoluene, chlorinating it to form o-chlorobenzyl chloride, hydrolyzing it to form o-chlorobenzaldehyde, reacting it with acetic acid in a sodium acetate solution to form o-chlorocinnamic acid, hydrogenating it, and hydrolyzing it in an alkaline aqueous solution to form o-hydroxybenzene propionic acid, and then dehydrating and cyclizing; (4) Using o-methylphenol as a raw material, reacting it with phosphorus oxychloride, then chlorinating it, reacting it with sodium ethoxide at 160 - 180 °C to form coumarin, and finally hydrogenating it. Summary of the Invention

[0004] The technical problem to be solved by the present invention is to provide a method for preparing dihydrocoumarin compounds, which has simple operation, high yield, and is easy to scale up production.

[0005] The technical problem to be solved by the present invention is achieved through the following technical solutions:

[0006] A method for preparing dihydrocoumarin compounds, comprising the following steps:

[0007] (1) In a reaction flask, successively add raw material I, a photocatalyst, an auxiliary agent, and a solvent;

[0008] (2) After the reaction system is stirred evenly, react it at 40 - 60 °C for 12 - 48 h under light irradiation conditions;

[0009] (3) After the reaction is completed, add dichloromethane and saturated NaCl solution for washing, extract and separate to obtain an organic phase, and dry it with anhydrous Na 2 SO 4 Dry, distill off the solvent under reduced pressure, and purify it by silica gel column chromatography to obtain the corresponding dihydrocoumarin compound II.

[0010] The reaction formula is as follows:

[0011]

[0012] Among them, in the above reaction, R 1 is one of hydrogen, methyl, and phenyl; R 2 is one of hydrogen, chlorine, and bromine atoms.

[0013] Preferably, the photocatalyst in step (1) is one of cobalt iodide, cobalt hydroxide, or cobalt acetate, and the molar ratio of the photocatalyst to raw material I is (0.01 - 0.10):1.

[0014] Preferably, the assistant in step (1) is one or more of tetrabutylammonium bromide, tetrabutylammonium iodide, pivalic acid, isovaleric acid, or cesium carbonate, and the molar ratio of the assistant to raw material I is (0.1 - 2.0):1.

[0015] Preferably, the solvent in step (1) is one or more of n-hexane, cyclohexane, n-heptane, or cycloheptane.

[0016] Preferably, raw material I in step (1) is a dihydrobenzopyran compound.

[0017] Preferably, in step (2), the wavelength range of the light irradiation is 400 - 450 nm.

[0018] The above technical solution of the present invention has the following beneficial effects:

[0019] This technical solution uses a dihydrobenzopyran compound as a raw material, and undergoes a photocatalytic oxidation reaction under light irradiation to obtain a dihydrocoumarin compound. The reaction process of the present invention is simple, without the use of metal reagents and oxidants, the reaction yield is up to 85%, and the post-treatment is simple and easy to operate, having good application prospects. Detailed Embodiments

[0020] Now, various exemplary embodiments of the present invention will be described in detail. It should be noted that: Unless otherwise specifically stated, the relative arrangements, numerical expressions, and numerical values of the components and steps set forth in these embodiments do not limit the scope of the present invention.

[0021] Example 1

[0022] A method for preparing a dihydrocoumarin compound, comprising the following steps:

[0023] (1) In a 10 mL round-bottom flask, successively add dihydrobenzopyran (134 mg, 1.0 mmol), catalyst cobalt iodide (16 mg, 0.05 mmol), tetrabutylammonium iodide (37 mg, 0.1 mmol), pivalic acid (12 mg, 0.1 mmol), and n-hexane (2 mL);

[0024] (2) Stir at 20 °C until completely dissolved, and then react at 60 °C for 36 h under 400 nm light irradiation;

[0025] (3) After the reaction was completed, 10 mL of dichloromethane and 10 mL of saturated NaCl solution were added for washing. The organic phase was obtained by extraction and separation and dried with anhydrous Na 2 SO 4 sulfate. The solvent was removed by distillation under reduced pressure and purified by silica gel column chromatography to obtain 126 mg of dihydrocoumarin with a yield of 85%.

[0026] Example 2

[0027] A method for preparing a dihydrocoumarin compound, comprising the following steps:

[0028] (1) In a 10 mL round-bottom flask, dihydrobenzopyran (134 mg, 1.0 mmol), cobalt hydroxide catalyst (5 mg, 0.05 mmol), tetrabutylammonium bromide (32 mg, 0.1 mmol), isovaleric acid (24 mg, 0.2 mmol) and cyclohexane (2 mL) were added in sequence;

[0029] (2) Stir at 20 °C until completely dissolved, and then react at 40 °C for 48 h under 400 nm light irradiation;

[0030] (3) After the reaction was completed, 10 mL of dichloromethane and 10 mL of saturated NaCl solution were added for washing. The organic phase was obtained by extraction and separation and dried with anhydrous Na 2 SO 4 sulfate. The solvent was removed by distillation under reduced pressure and purified by silica gel column chromatography to obtain 121 mg of dihydrocoumarin with a yield of 82%.

[0031] Example 3

[0032] A method for preparing a dihydrocoumarin compound, comprising the following steps:

[0033] (1) In a 20 mL round-bottom flask, dihydrobenzopyran (134 mg, 1.0 mmol), cobalt acetate catalyst (9 mg, 0.05 mmol), tetrabutylammonium iodide (37 mg, 0.2 mmol), pivalic acid (12 mg, 0.1 mmol) and n-heptane (2 mL) were added in sequence;

[0034] (2) Stir at 20 °C until completely dissolved, and then react at 50 °C for 36 h under 400 nm light irradiation.

[0035] (3) After the reaction was completed, 10 mL of dichloromethane and 10 mL of saturated NaCl solution were added for washing. The organic phase was obtained by extraction and separation and dried with anhydrous Na 2 SO 4 sulfate. The solvent was removed by distillation under reduced pressure and purified by silica gel column chromatography to obtain 118 mg of dihydrocoumarin with a yield of 80%.

[0036] Compound structure characterization: Dihydrocoumarin: 1 H NMR(600MHz,CDCl 3 )δ 7.25(m,2H),7.15(m,1H),7.04(m,1H),3.01(t,J = 7.1Hz,2H),2.78(t,J = 7.1Hz,2H). 13 C NMR(150MHz,CDCl 3 )δ 168.0,152.1,129.6,126.4,125.3,122.8,116.7,28.4,23.6.

[0037] Although the present invention has been disclosed above by way of examples, it is not intended to limit the present invention. Any person skilled in the art can make various different selections and modifications without departing from the spirit and scope of the present invention. Therefore, the protection scope of the present invention is defined by the claims and their equivalent forms.

Claims

1. A method for preparing a dihydrocoumarin compound, characterized in that, it comprises the following steps: (1) In a reaction flask, successively add raw material I, a photocatalyst, an auxiliary agent and a solvent; raw material I is a dihydrobenzopyran compound; the photocatalyst is one of cobalt iodide, cobalt hydroxide or cobalt acetate; the auxiliary agent is multiple of tetrabutylammonium bromide, tetrabutylammonium iodide, pivalic acid, isovaleric acid; the solvent is one or more of n-hexane, cyclohexane, n-heptane or cycloheptane; (2) After the reaction system is stirred evenly, under the condition of light irradiation, react at 40-60 °C for 12-48 h; After the reaction was completed, dichloromethane and saturated NaCl solution were added for washing. The organic phase was separated by extraction and dried over anhydrous Na 2 SO 4 Then the solvent was removed by distillation under reduced pressure, and the product was purified by silica gel column chromatography to obtain the corresponding dihydrocoumarin compound II; The reaction formula is as follows: ， Among them, in the above reaction, R 1 is one of hydrogen, methyl, and phenyl; R 2 is one of hydrogen, chlorine, and bromine atoms.

2. The method for preparing a dihydrocoumarin compound according to claim 1, characterized in that, the molar ratio of the photocatalyst to raw material I in step (1) is (0.01-0.10):

1.

3. The method for preparing a dihydrocoumarin compound according to claim 1, characterized in that, the molar ratio of the auxiliary agent to raw material I in step (1) is (0.1-2.0):

1.

4. The method for preparing a dihydrocoumarin compound according to claim 1, characterized in that, in step (2), the wavelength range of the light irradiation is 400-450 nm.

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