Preparation method of cardanol

Abstract

The invention relates to a preparation method of a cardanol compound 2. The reaction is as follows: # imgabs0 # R'is selected from H, carboxyl, halogen or halogen substituted C1-4 alkyl, and halogen is selected from fluorine, chlorine, bromine and iodine; comprising the following steps: (1) reacting a compound of formula 1 in the presence of sodium ethanethiol and inorganic base to obtain a compound 2; the preparation method provided by the invention is mild in process condition, simple and convenient to operate, high in yield, simple in post-treatment and suitable for industrial large-scale production.

Description

Technical Field

[0001] The invention relates to a method for preparing cardanol, and belongs to the technical field of medicine and chemistry. Background Art

[0002] Cardanol is extracted from natural cashew shell liquid and is a biomass energy raw material. It can replace phenolic chemical raw materials such as phenol to synthesize non-toxic and environmentally friendly polymer biomaterials. Cardanol is used in resins, coatings, friction materials and surfactants in the chemical industry, and as a pigment dispersant for water-based inks. It is used to make phenalkamines, which are used as curing agents for durable epoxy coatings used on concrete floors. The structure is shown below:

[0003]

[0004] [Journal of Chemical Research, Miniprint, 1982, 2, p. 321-351] discloses a method for preparing the compound by reacting with boron tribromide in dichloromethane at -70°C. Boron tribromide is a toxic, corrosive, fuming liquid with a pungent, irritating odor, and needs to be reacted at -70°C, which is not conducive to industrial scale-up. The synthetic route is as follows:

[0005]

[0006] There are few existing methods for synthesizing cardanol, and the synthesis process involves ultra-low temperature reaction, which is not conducive to industrial production. Therefore, it is currently necessary to develop a new method for preparing cardanol. Summary of the invention

[0007] In view of the defects of the prior art, the invention aims to solve the problem of providing a method for producing cardanol safely and cheaply with high yield. The method is simple, efficient, reduces costs, and is conducive to large-scale industrial production.

[0008] In order to achieve the above technical objectives, the present invention adopts the following technical solutions:

[0009] The present invention provides a method for preparing cardanol, and the reaction is as follows:

[0010]

[0011] R' is selected from H, carboxyl, halogen or halogen substituted C 1-4 Alkyl, halogen is selected from fluorine, chlorine, bromine and iodine;

[0012] The steps include:

[0013] (1) The compound of formula 1 is reacted in the presence of sodium ethanethiolate and an inorganic base to obtain compound 2.

[0014] As a further improvement of the present invention, including but not limited to, the molar ratio of the inorganic base to the compound of formula 1 in the reaction of step (1) is 1:(1-5), preferably 1:(1-1.5);

[0015] As a further improvement of the present invention, including but not limited to, the inorganic base participates in the reaction in the form of a solid or an inorganic base aqueous solution, and the molar concentration of the inorganic base aqueous solution can be 0.5 to 2 mol / L, preferably 0.5 to 1 mol / L;

[0016] As a further improvement of the present invention, including but not limited to, the inorganic base is selected from one or more of alkali metal hydroxides, alkali metal carbonates, alkali metal bicarbonates and alkali metal phosphates;

[0017] As a further improvement of the present invention, including but not limited to, the alkali metal hydroxide is lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide or cesium hydroxide, preferably sodium hydroxide or potassium hydroxide;

[0018] As a further improvement of the present invention, including but not limited to, the alkali metal carbonate is lithium carbonate, sodium carbonate, potassium carbonate, rubidium carbonate or cesium carbonate, preferably sodium carbonate or cesium carbonate;

[0019] As a further improvement of the present invention, including but not limited to, the alkali metal bicarbonate is lithium bicarbonate, sodium bicarbonate, potassium bicarbonate, rubidium bicarbonate or cesium bicarbonate, preferably sodium bicarbonate or potassium bicarbonate;

[0020] As a further improvement of the present invention, including but not limited to, the alkali metal phosphate is lithium phosphate, sodium phosphate, potassium phosphate, rubidium phosphate or cesium phosphate, preferably sodium phosphate or potassium phosphate;

[0021] As a further improvement of the present invention, including but not limited to, the molar ratio of sodium ethanethiolate to the compound of formula 1 in the reaction of step (1) is (2-12):1, preferably (6-8.5):1, for example 7.5:1;

[0022] As a further improvement of the present invention, including but not limited to, the reaction in step (1) is carried out in an organic solvent.

[0023] As a further improvement of the present invention, including but not limited to, the organic solvent is one or more of ether solvents, ketone solvents, aromatic hydrocarbon solvents, nitrile solvents, sulfone solvents and amide solvents, preferably one or more of nitrile solvents, sulfone solvents and amide solvents; the nitrile solvent is preferably acetonitrile; the sulfone solvent is preferably dimethyl sulfoxide; the amide solvent can be one or more of N,N-dimethylformamide, N-methylpyrrolidone and N,N-dimethylacetamide, preferably N,N-dimethylformamide; the ether solvent can be one or more of tetrahydrofuran, methyltetrahydrofuran and dioxane, preferably tetrahydrofuran or methyltetrahydrofuran; the ketone solvent can be acetone; the aromatic hydrocarbon solvent can be one or both of toluene and pyridine, preferably toluene;

[0024] As a further improvement of the present invention, including but not limited to, the present invention preferably uses an organic solvent, which is mainly selected from the viewpoints of reactivity, selectivity and ease of availability; the organic solvent in step (1) is selected from one or more of tetrahydrofuran, 2-methyltetrahydrofuran, acetone, toluene, acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide or N,N-dimethylacetamide, preferably N,N-dimethylformamide.

[0025] As a further improvement of the present invention, including but not limited to, from the viewpoint of productivity and reactivity, the volume amount of the organic solvent mL is generally 1 to 20 times, preferably 2 to 16 times, and particularly preferably 6 to 12 times relative to the mass amount g of the compound of Formula 1;

[0026] As a further improvement of the present invention, including but not limited to, from the viewpoint of reactivity and productivity, the reaction temperature of step (1) of the present invention is 90 to 150° C., preferably 125 to 145° C. When the reaction temperature is too low, the reactivity may decrease, and conversely, when it is too high, side reactions may occur, resulting in a decrease in yield and selectivity.

[0027] As a further improvement of the present invention, including but not limited to, the reaction time of step (1) is 5 to 24 hours, preferably 12 to 18 hours;

[0028] As a further improvement of the present invention, including but not limited to, after the reaction of step (1) is completed, post-treatment can be selectively performed. For example, the organic layer obtained by extraction with an organic solvent can be dried, concentrated, etc. Further, purification is performed by recrystallization, chromatography, etc. For example: after the reaction is completed, water is added for washing, organic solvent is used for extraction, liquid separation is performed, the organic phase is concentrated under reduced pressure, and column chromatography is used for purification to obtain the product.

[0029] Beneficial technical effects of the present invention:

[0030] According to the method for producing cardanol of the present invention, cardanol can be produced safely at a high yield and at a low cost.

[0031] The inventors of the present application have found that protection and deprotection of phenolic hydroxyl groups are often encountered in organic synthesis. If methyl is used as a protecting group for phenolic hydroxyl groups, methyl aryl ether is formed, and then the phenolic hydroxyl groups are reduced by demethylation. The types of general demethylation agents can be divided into:

[0032] 1. Acidic demethylation reagents, common acidic demethylation reagents include boron tribromide, aluminum trichloride, hydrobromic acid, sulfuric acid, etc. The substrate of the present invention [Journal of Chemical Research, Miniprint, 1982, 2, p.321-351] reacts with boron tribromide in dichloromethane at -70°C for 3 hours. The reaction conditions are harsh and the equipment requirements are extremely high.

[0033] 2. Other conditions Demethylation reagent, taking trimethyl iodosilane as an example, aryl methyl ether and trimethyl iodosilane are used to generate aryl silyl ether, and then demethylation product is obtained through deprotection reaction. This reaction reagent is expensive.

[0034] 3. Alkaline demethylation reagent, using alkaline demethylation reagent to remove methyl, common alkaline demethylation reagents include sodium ethanethiolate, sodium amide, etc. Most of the similar substrates of the present invention use NaH+EtSH to generate sodium ethanethiolate, and then reflux reaction. The prior art cardanol-like substrates do not use alkali metal bicarbonate, alkali metal carbonate or alkali metal hydroxide, and there is no teaching to use sodium ethanethiolate and alkali metal bicarbonate, alkali metal carbonate or alkali metal hydroxide to act together in the deprotection reaction of the cardanol substrate of the present application.

[0035] The inventors of the present application also found that Berichte der Deutschen Chemischen Gesellschaft (1901), 34, 1812 reported that the yield of anisole deprotection in potassium hydroxide / ethanol was only 11%.

[0036] The present invention aims to provide a preparation method with mild process conditions, simple operation, high yield, simple post-treatment, and is suitable for industrialized production. The prior art uses NaH and EtSH to reflux in DMF for 3 hours for demethylation of similar structures, and the yield is only 73%. The inventors repeated the reaction conditions of NaH and EtSH in the prior art in Example 1 and Comparative Example 2, and the yield was only 6.9%. The present invention can increase the yield to 87.69% under the joint action of sodium ethanethiolate and an inorganic base, and the obtained product has high quality and good reproducibility.

[0037] In Comparative Example 3 and Comparative Example 4, the inventors used sodium ethanethiolate without adding alkali, and the yield was less than 15%; therefore, the preparation method provided by the present invention obtains unexpected technical effects, greatly improves the yield, can obtain products with high yield and high quality, and is conducive to industrial scale-up production. DETAILED DESCRIPTION

[0038] The preparation method of the present invention will be described in further detail below in conjunction with specific examples. It should be understood that the following examples are only exemplary illustrations and explanations of the present invention and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are included in the scope that the present invention is intended to protect.

[0039] Unless otherwise specified, the experimental methods used in the following examples are all conventional methods; the reagents, materials, etc. used in the following examples, unless otherwise specified, can be obtained from commercial channels.

[0040] Embodiment 1:

[0041]

[0042] Compound 1 (5 g, 15.8 mmol) was dissolved in DMF (50 mL), and cesium carbonate (6.69 g, 20.5 mmol) and sodium ethanethiolate (9.97 g, 118.5 mmol) were added in sequence, and the temperature was raised to 140°C and stirred overnight. The mixture was washed with water, extracted with ethyl acetate, and the organic phase was washed with a saturated sodium chloride solution. The organic phase was separated, dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography to obtain a yellow oily liquid compound 2 (4.19 g, yield 87.69%).

[0043] Comparative Example 1

[0044]

[0045] The temperature was controlled at 0°C in an ice bath, NaH (166.79 mg, 60% purity, 4.17 mmol) was added to DMF (3 mL), and ethanethiol (260 mg, 4.18 mmol) was added dropwise under argon protection. After the addition, the ice bath was removed and stirred at 25°C for 30 min, followed by the addition of a DMF (3 mL) solution of compound 1 (440 mg, 1.39 mmol), the temperature was raised to 140°C, and refluxed for 3 hours. TLC detected the disappearance of compound 1 and no obvious main point. Wash with water, extract with ethyl acetate, wash the organic phase with a saturated sodium chloride solution, separate the organic phase, dry over anhydrous sodium sulfate, concentrate, and separate by column chromatography to obtain a yellow oily liquid compound 2 (29 mg, yield 6.9%).

[0046] Comparative Example 2

[0047]

[0048] The temperature was controlled at 0°C in an ice bath, NaH (166.79 mg, 60% purity, 4.17 mmol) was added to DMF (3 mL), and ethanethiol (260 mg, 4.2 mmol) was added dropwise under argon protection. After the addition, the ice bath was removed and stirred at 25°C for 30 min, followed by the addition of a DMF (3 mL) solution of compound 1 (260 mg, 4.18 mmol), the temperature was raised to 140°C, and refluxed overnight. TLC detected the disappearance of compound 1 and no obvious main point. Wash with water, extract with ethyl acetate, wash the organic phase with a saturated sodium chloride solution, separate the organic phase, dry over anhydrous sodium sulfate, concentrate, and separate by column chromatography to obtain a yellow oily liquid compound 2 (52 mg, 12.4%).

[0049] Comparative Example 3

[0050]

[0051] Compound 1 (0.5 g, 1.58 mmol) was dissolved in DMF (5 mL), followed by the addition of sodium ethanethiolate (398.6 mg, 4.74 mmol), the temperature was raised to 140°C, and the mixture was stirred overnight. The compound 1 disappeared by TLC detection, and no obvious main point was observed. The mixture was washed with water, extracted with ethyl acetate, and the organic phase was washed with a saturated sodium chloride solution. The organic phase was separated, dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography to obtain a yellow oily liquid compound 2 (67 mg, 14.02%).

[0052] Comparative Example 4

[0053]

[0054] Compound 1 (0.5 g, 1.58 mmol) was dissolved in DMF (5 mL), followed by the addition of sodium ethanethiolate (997.7 mg, 11.86 mmol), the temperature was raised to 140°C, and the mixture was stirred overnight. The compound 1 disappeared by TLC detection, and no obvious main point was observed. The mixture was washed with water, extracted with ethyl acetate, and the organic phase was washed with a saturated sodium chloride solution. The organic phase was separated, dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography to obtain a yellow oily liquid compound 2 (71 mg, 14.86%).

Claims

1. A method for preparing cardanol, the reaction formula is as follows: R' is selected from H, carboxyl, halogen or halogen substituted C 1-4 Alkyl, halogen is selected from fluorine, chlorine, bromine and iodine; The steps include: (1) The compound of formula 1 is reacted in the presence of sodium ethanethiolate and an inorganic base to obtain compound 2.

2. The preparation method according to claim 1, characterized in that: In the reaction of step (1), the molar ratio of the inorganic base to the compound of formula 1 is 1:(1-5), preferably 1:(1-1.5).

3. The preparation method according to claim 1 or 2, characterized in that: The inorganic base is reacted in the form of a solid or an aqueous solution of the inorganic base. The molar concentration of the aqueous solution of the inorganic base can be 0.5 to 2 mol / L, preferably 0.5 to 1mol / L.

4. The preparation method according to claim 1 or 2, characterized in that: The inorganic base is selected from one or more of alkali metal hydroxides, alkali metal carbonates, alkali metal bicarbonates and alkali metal phosphates.

5. The preparation method according to claim 4, characterized in that: The alkali metal hydroxide is lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide or cesium hydroxide, preferably sodium hydroxide or potassium hydroxide; And / or, preferably, the alkali metal carbonate is lithium carbonate, sodium carbonate, potassium carbonate, rubidium carbonate or cesium carbonate, preferably sodium carbonate or cesium carbonate; And / or, preferably, the alkali metal bicarbonate is lithium bicarbonate, sodium bicarbonate, potassium bicarbonate, rubidium bicarbonate or cesium bicarbonate, preferably sodium bicarbonate or potassium bicarbonate; And / or, preferably, the alkali metal phosphate is lithium phosphate, sodium phosphate, potassium phosphate, rubidium phosphate or cesium phosphate, preferably sodium phosphate or potassium phosphate.

6. The preparation method according to claim 1 or 2, characterized in that: In the reaction of step (1), the molar ratio of sodium ethanethiolate to the compound of formula 1 is (2-12):1, preferably (6-8.5):1, for example 7.5:

1.

7. The preparation method according to claim 1 or 2, characterized in that: The preparation method of cardanol meets one or more of the following conditions: 1) The volume amount of the organic solvent, mL, is usually 1 to 20 times, preferably 2 to 16 times, and particularly preferably 6 to 12 times, relative to the mass amount of the compound of Formula 1, g; 2) The reaction temperature of step (1) is 90-150°C, preferably 125-145°C; 3) The reaction time of step (1) is 5 to 24 hours, preferably 12 to 18 hours.

8. The preparation method according to claim 1 or 2, characterized in that: The reaction in step (1) is carried out in an organic solvent.

9. The preparation method according to claim 8, characterized in that: The organic solvent is one or more of ether solvents, ketone solvents, aromatic hydrocarbon solvents, nitrile solvents, sulfone solvents and amide solvents, preferably one or more of nitrile solvents, sulfone solvents and amide solvents; the nitrile solvent is preferably acetonitrile; the sulfone solvent is preferably dimethyl sulfoxide; the amide solvent may be one or more of N,N-dimethylformamide, N-methylpyrrolidone and N,N-dimethylacetamide, preferably N,N-dimethylformamide; the ether solvent may be one or more of tetrahydrofuran, methyltetrahydrofuran and dioxane, preferably tetrahydrofuran or methyltetrahydrofuran; the ketone solvent may be acetone; the aromatic hydrocarbon solvent may be one or both of toluene and pyridine, preferably toluene; And / or, preferably, the organic solvent in step (1) is selected from one or more of tetrahydrofuran, 2-methyltetrahydrofuran, acetone, toluene, acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide or N,N-dimethylacetamide, preferably N,N-dimethylformamide.

10. The preparation method according to claim 1 or 2, characterized in that: After the reaction in step (1) is completed, post-treatment can be selectively performed; the organic layer obtained by extraction with an organic solvent can be dried and concentrated; further, it can be purified by recrystallization and chromatography; preferably, after the reaction is completed, water is added for washing, organic solvent is used for extraction, liquid separation is performed, the organic phase is concentrated under reduced pressure, and column chromatography is used for purification to obtain the product.

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