Synthesis method of lily alcohol

Abstract

The invention belongs to the technical field of organic synthesis, and particularly discloses a synthesis method of convallaryl alcohol, which comprises the following steps: (1) at room temperature, limonene is subjected to catalytic hydrogenation to obtain p-menthene; (2) reacting menthene with trimethyltin chloride under the action of organic alkali to obtain an organic tin compound, and hydrolyzing the organic tin compound to obtain 1-isopropyl-4-methylene cyclohexane; (3) adding 1-isopropyl-4-methylene cyclohexane into 9-boron bicyclo [3, 3, 1]-nonane, and carrying out a heating reflux reaction; and after the reaction is finished, sequentially adding ethanol, a sodium hydroxide solution and hydrogen peroxide to oxidize the generated organic boron compound, and finally extracting and drying to obtain the product lily alcohol. The limonene is used as a raw material, the raw material is cheap and easy to obtain, the reaction process is mild and easy to operate, the problem of hydrogenation under high-temperature and high-pressure conditions in the prior art can be effectively avoided, and a new method is provided for synthesis of the lily alcohol.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, relates to the synthesis of a fragrance intermediate, and specifically relates to a method for synthesizing lily of the valley alcohol. Background Art

[0002] May lily alcohol is 4-(1-methylethyl)-cyclohexylmethanol, also known as 7-hydroxy Alkane is an organic compound. Lily of the valley alcohol is a transparent colorless liquid with a fresh and soft special floral fragrance. It contains a mixture of cis-isomers, mainly cis-isomers. In commercial applications, cis-isomers account for 60-80% and trans-isomers account for 20-40%. Lily of the valley alcohol is a fragrance ingredient used in cosmetics, high-end perfumes, shampoos, soaps and other toiletries.

[0003] In 2006, an article from Patrick Diter's laboratory mentioned that 4-isopropyl cyclohexanoic acid was obtained by catalytic hydrogenation of 4-isopropyl benzoic acid as a raw material, and then lily of the valley alcohol was obtained by lithium aluminum hydride reduction (New Journal of Chemistry, 2006, 30, 447-457).

[0004] At present, the synthesis method of lily of valley alcohol in the industry is mainly to use cuminaldehyde as the starting material and obtain it through catalytic hydrogenation. An international patent WO 2011082991A2 published by BASF discloses a synthesis method of lily of valley alcohol, that is, using a self-made catalyst to directly hydrogenate cuminaldehyde at 160°C and a hydrogen pressure of 20MPa using a hydrogenation catalyst, and the obtained product is also a mixture of cis and trans isomers. International patent WO 2010079035A2 discloses a process for preparing lily of valley alcohol using cuminaldehyde as a raw material in a continuous flow reactor. They made a catalyst and filled it in a fixed bed for continuous flow hydrogenation to prepare lily of valley alcohol.

[0005]

[0006] As can be seen from the above, the current industrial method for synthesizing valerianol is basically to use cuminaldehyde as a raw material for hydrogenation catalysis under high temperature and high hydrogen pressure conditions, and the production method is relatively simple. Therefore, it is necessary to develop a more novel method for synthesizing valerianol. Summary of the invention

[0007] In view of the shortcomings of the prior art, the purpose of the present invention is to provide a method for synthesizing lily of the valley alcohol. The present invention uses limonene as a raw material, has a mild reaction and is easy to operate, and can effectively avoid the problem of hydrogenation under high temperature and high pressure conditions in the prior art.

[0008] The present invention is achieved through the following technical solutions:

[0009] A method for synthesizing lily of the valley alcohol comprises the following steps:

[0010] (1) At room temperature, limonene is subjected to catalytic hydrogenation to obtain p-menthene; wherein limonene is represented by formula (1) and p-menthene is represented by formula (2);

[0011] (2) reacting menthene with trimethyltin chloride in the presence of an organic base to obtain an organic tin compound, which is hydrolyzed to obtain 1-isopropyl-4-methylenecyclohexane; the organic tin compound is represented by formula (3), and 1-isopropyl-4-methylenecyclohexane is represented by formula (4);

[0012]

[0013] (3) adding 1-isopropyl-4-methylenecyclohexane to 9-borabicyclo[3,3,1]-nonane and heating under reflux for reaction; after the reaction is completed, adding ethanol, sodium hydroxide solution and hydrogen peroxide in sequence to oxidize the generated organic boron compound, and finally extracting and drying to obtain the product lily of the valley alcohol.

[0014] The reaction route is as follows:

[0015]

[0016] The present invention is further improved as follows:

[0017] Furthermore, in step (1), the catalyst for catalytic hydrogenation is one or a mixture of two or more of palladium carbon, ruthenium carbon, Raney nickel or platinum dioxide.

[0018] Furthermore, in step (1), the solvent for the catalytic hydrogenation is one or a mixture of two or more of methanol, ethyl acetate or tetrahydrofuran.

[0019] Furthermore, the amount of the catalyst used is 0.25% to 2% of the mass of limonene.

[0020] Furthermore, in step (2), the organic base is a mixture of n-butyl lithium and N,N,N',N'-tetramethylethylenediamine.

[0021] Furthermore, in step (2), the n-butyl lithium and N,N,N',N'-tetramethylethylenediamine are slowly added dropwise at -80°C to -70°C, and the subsequent addition of trimethyltin chloride is carried out at -5°C to 5°C, wherein the solvent for the n-butyl lithium is n-hexane.

[0022] Furthermore, in step (2), the equivalent ratio of n-butyl lithium, N,N,N',N'-tetramethylethylenediamine and p-menthene is (0.5-1.5):(0.5-1.5):2.

[0023] Furthermore, in step (3), the equivalent ratio of 9-boranebicyclo[3,3,1]-nonane to 1-isopropyl-4-methylenecyclohexane is 1:(1.1-1.5).

[0024] The beneficial effects of the present invention are:

[0025] The invention uses limonene as a raw material, which is cheap and easily available, and the reaction process is mild and easy to operate. The problem of hydrogenation under high temperature and high pressure conditions in the prior art can be effectively avoided, and a new method for the synthesis of lily of the valley alcohol is provided. DETAILED DESCRIPTION

[0026] The present invention is described in detail below in conjunction with specific embodiments.

[0027] Example 1

[0028] 5% palladium carbon (0.068 g) was added to the reaction bottle to replace the hydrogen three times, and then limonene (13.63 g, 100 mmol) and 50 mL of methanol were added. The reaction was carried out at room temperature for 4 hours under a 0.1 MPa hydrogen environment. The palladium carbon catalyst was filtered out and the methanol was removed by distillation under reduced pressure to obtain the product p-menthene with a yield of 71%.

[0029] In a nitrogen atmosphere at -78°C, N,N,N',N'-tetramethylethylenediamine (5mL, 5.0M, 25mmol) was slowly added dropwise to a solution of n-butyllithium (10mL, 2.5M, 25mmol). After the reaction system was warmed to room temperature, p-menthene (6.92g, 50mmol) was added and stirred at room temperature for 36h. Then the reactants were cooled to 0°C, and a n-hexane solution of trimethyltin chloride (7mL, 5M, 35mmol) was added to the reaction system. The reaction system was reacted at 70°C for 4h, and then a saturated aqueous solution of ammonium chloride was added. The organic phase was dried over anhydrous magnesium sulfate and concentrated by distillation to obtain the product 1-isopropyl-4-methylenecyclohexane with a yield of 72%.

[0030] 1-Isopropyl-4-methylenecyclohexane (6.92 g, 50 mmol) was added to a tetrahydrofuran solution of 9-borabicyclo[3,3,1]-nonane (10 mL, 4.5 M, 45 mmol) and heated to reflux at 60°C for 8 h. After the reaction was completed, 30 mL of ethanol, 10 mL of sodium hydroxide solution (6 mol / L) and 30% hydrogen peroxide were added in sequence and heated at 50°C for 1 h to oxidize the generated organic boron compound. After cooling, the aqueous phase was extracted with ethyl acetate and washed three times. After drying with anhydrous magnesium sulfate, the product lily of the valley alcohol was obtained by filtration and distillation with a yield of 74%.

[0031] Example 2

[0032] 0.1% platinum dioxide (0.034 g) was added to the reaction flask to replace hydrogen three times, and then limonene (13.63 g, 100 mmol) and 50 mL of methanol were added. The reaction was carried out at room temperature for 4 hours under a 0.1 MPa hydrogen environment, and the platinum dioxide catalyst was filtered out and the methanol was removed by vacuum distillation to obtain the product p-menthene with a yield of 63%. The product lily of the valley alcohol was subsequently obtained according to the method of Example 1.

[0033] Example 3

[0034] Raney nickel (0.041 g) was added to the reaction flask to replace hydrogen three times, and then limonene (13.63 g, 100 mmol) and 50 mL of methanol were added. The reaction was carried out at room temperature for 4 h under a 0.1 MPa hydrogen environment, and the Raney nickel catalyst was removed by filtration. The methanol was removed by reduced pressure distillation to obtain the product p-menthene with a yield of 78%. Subsequently, the product lily of the valley alcohol was obtained according to the method of Example 1.

[0035] The above embodiments are only for illustrating the technical concept and features of the present invention, and their purpose is to enable people familiar with the technology to understand the content of the present invention and implement it accordingly, and they cannot be used to limit the protection scope of the present invention. Any equivalent transformation or modification made according to the spirit of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for synthesizing lily of the valley alcohol, characterized in that: The following steps are involved: (1) At room temperature, limonene is catalytically hydrogenated to obtain p-menthene; (2) reacting menthene with trimethyltin chloride under the action of an organic base to obtain an organic tin compound, and hydrolyzing the organic tin compound to obtain 1-isopropyl-4-methylenecyclohexane; (3) adding 1-isopropyl-4-methylenecyclohexane to 9-borabicyclo[3,3,1]-nonane and heating under reflux for reaction; after the reaction is completed, adding ethanol, sodium hydroxide solution and hydrogen peroxide in sequence to oxidize the generated organic boron compound, and finally extracting and drying to obtain the product lily of the valley alcohol.

2. A method for synthesizing lycopersicon esculentum according to claim 1, characterized in that: In step (1), the catalyst for catalytic hydrogenation is one or a mixture of two or more of palladium carbon, ruthenium carbon, Raney nickel or platinum dioxide.

3. A method for synthesizing lycopersicon esculentum according to claim 1, characterized in that: In step (1), the solvent for catalytic hydrogenation is one or a mixture of two or more of methanol, ethyl acetate or tetrahydrofuran.

4. A method for synthesizing lycopersicon esculentum according to claim 1 or 2, characterized in that: The amount of the catalyst used is 0.25% to 2% of the mass of limonene.

5. The method for synthesizing lycopersicol according to claim 1, characterized in that: In step (2), the organic base is a mixture of n-butyl lithium and N,N,N',N'-tetramethylethylenediamine.

6. The method for synthesizing lycopersicol according to claim 5, characterized in that: In step (2), the n-butyl lithium and N,N,N',N'-tetramethylethylenediamine are slowly added dropwise at -80°C to -70°C, and the subsequent addition of trimethyltin chloride is carried out at -5°C to 5°C, wherein the solvent for the n-butyl lithium is n-hexane.

7. The method for synthesizing lily of may alcohol according to claim 1, characterized in that: In step (2), the equivalent ratio of n-butyl lithium, N,N,N',N'-tetramethylethylenediamine and p-menthene is (0.5-1.5):(0.5-1.5):

2.

8. The method for synthesizing lycopersicol according to claim 1, characterized in that: In step (3), the equivalent ratio of 9-boranebicyclo[3,3,1]-nonane to 1-isopropyl-4-methylenecyclohexane is 1:(1.1-1.5).

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