A method for synthesizing santalol

Abstract

The application discloses a method for synthesizing santalol, which comprises the following steps: 1) dispersing santalene, N-bromosuccinimide, benzoyl peroxide and aminated carbon material in an organic solvent to perform a substitution reaction, so as to obtain brominated santalene; 2) dispersing the brominated santalene and sodium peroxoacetate in an organic solvent to perform an esterification reaction, so as to obtain santalene acetic acid ester; and 3) dispersing the santalene acetic acid ester and lithium hydroxide monohydrate in a methanol aqueous solution to perform a hydrolysis reaction, so as to obtain santalol. The method for synthesizing santalol has the advantages of simple operation process, short reaction time, mild reaction condition, high raw material conversion rate, high product yield, high product selectivity, green environmental protection and the like, and is suitable for large-scale industrial application.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and specifically to a method for synthesizing santalol. Background Technology

[0002] Santalol is the most important sesquiterpene aromatic component in sandalwood oil, mainly including (Z)-α-santalol and (Z)-β-santalol. Together, they give sandalwood oil its deep, warm, and long-lasting typical woody and balsam-like aroma. Sandalwood oil is considered liquid gold and is widely used in high-end perfumes, cosmetics, pharmaceuticals, and incense.

[0003] Natural sandalwood oil is obtained by distilling the heartwood of sandalwood (Santalum album L.), containing approximately 45%–75% santalol, with the remainder being trace components such as epi-β-santalol and bergamot. However, natural sandalwood resources face three major technological bottlenecks: 1) Sandalwood grows extremely slowly, requiring 20–40 years to mature, and over-harvesting has led to a scarcity and high price of raw materials; 2) Differences in climate and origin result in large annual fluctuations in the quality of sandalwood oil, with high-grade fragrance-grade sandalwood oil frequently out of supply; 3) Traditional plant extraction processes have low yields (≤4%) and generate large amounts of waste liquid (containing organic solvents) and wood waste, placing a heavy burden on the environment.

[0004] Currently, several synthetic routes for santalol using camphene, methyl norbornene, or farnesene as raw materials have been reported, which can synthesize racemic / chiral santalol and its dihydro and demethylated derivatives. However, existing chemical synthesis methods still have the following common problems: 1) The steps are lengthy (8 to 12 steps), the overall yield is low (<20%), and the production cost is high; 2) Some processes require the use of high-risk / high-polluting reagents such as BH3, Na / NH3, and Grignard reagent, posing a significant environmental risk; 3) Controlling the chiral center is difficult, the proportion of aroma-active isomers is low, and the aroma quality differs from that of natural sandalwood oil; 4) The Z / E selectivity of the side chain double bond and the construction of the exocyclic chiral center require expensive catalysts (e.g., Rh, Pd), increasing the production cost.

[0005] Therefore, it is of great significance to develop a method for synthesizing santalol that is simple in operation, short in reaction time, mild in reaction conditions, high in raw material conversion rate, high in product yield, high in product selectivity, and environmentally friendly. Summary of the Invention

[0006] The purpose of this invention is to provide a method for synthesizing santalol.

[0007] The technical solution adopted in this invention is: A method for synthesizing santalol, comprising the following steps: 1) A substitution reaction was carried out by dispersing santalene, N-bromosuccinimide (NBS), benzoyl peroxide (BPO) and aminated carbon material in an organic solvent to obtain bromosantalene; 2) Bromosanthene and sodium peracetate (NaOAc) were dispersed in an organic solvent and subjected to an esterification reaction to obtain santhrenyl acetate; 3) The santaloyl acetate and lithium hydroxide monohydrate (LiOH·H2O) were dispersed in an aqueous methanol solution and hydrolyzed to obtain santalol.

[0008] Preferably, the mass ratio of santalene to aminated carbon material in step 1) is 1:0.001 to 0.2.

[0009] More preferably, the mass ratio of santalene to aminated carbon material in step 1) is 1:0.02 to 0.1.

[0010] Preferably, the mass ratio of N-bromosuccinimide, benzoyl peroxide, and aminated carbon material in step 1) is 1-100:0.1-2:1.

[0011] More preferably, the mass ratio of N-bromosuccinimide, benzoyl peroxide, and aminated carbon material in step 1) is 5-50:0.2-2:1.

[0012] Preferably, the aminated carbon material in step 1) is at least one of aminated carbon nanotubes (N-CNTs), aminated graphene (NG), and aminated activated carbon (N-AC).

[0013] More preferably, the amination of carbon material in step 1) is amination of carbon nanotubes.

[0014] Preferably, the amination of the carbon material in step 1) is prepared by a method comprising the following steps: acid washing, water washing and drying of the carbon material, thionyl chloride (SOCl2) and pyridine are dispersed in a solvent for reaction, the carbon material is separated for water washing and drying, the carbon material, ethylenediamine and triethylamine are mixed for reaction, and the carbon material is separated for water washing and drying.

[0015] Preferably, the solvent used in the preparation of the aminated carbon material is N,N-dimethylformamide (DMF).

[0016] Preferably, the organic solvent in step 1) is at least one of dichloromethane and dichloroethane.

[0017] Preferably, the substitution reaction in step 1) is carried out at a temperature of 30°C to 150°C for a reaction time of 0.5 h to 12 h.

[0018] More preferably, the substitution reaction in step 1) is carried out at a temperature of 50°C to 90°C for a reaction time of 4 to 8 hours.

[0019] Preferably, the amount of sodium peracetate used in step 2) is 100% to 300% of the mass of santalene.

[0020] More preferably, the amount of sodium peracetate used in step 2) is 100% to 200% of the mass of sandalwoodene.

[0021] Preferably, the organic solvent in step 2) is at least one of ethyl acetate and methyl acetate.

[0022] Preferably, the esterification reaction in step 2) is carried out at a temperature of 70℃ to 90℃ for a reaction time of 3h to 7h.

[0023] Preferably, the amount of lithium hydroxide monohydrate used in step 3) is 10% to 100% of the mass of santalene.

[0024] More preferably, the amount of lithium hydroxide monohydrate used in step 3) is 20% to 50% of the mass of santalene.

[0025] Preferably, the hydrolysis reaction in step 3) is carried out at room temperature for 2 to 5 hours.

[0026] The reaction principle of this invention is as follows: using santalene as a substrate, N-bromosuccinimide (NBS) and benzoyl peroxide (BPO) as the main substitution reagents, and aminated carbon materials as catalysts, the allyl group of santalene is first brominated, and then further esterified and hydrolyzed to obtain santalol.

[0027] The beneficial effects of this invention are: the method for synthesizing santalol in this invention has the advantages of simple operation process, short reaction time, mild reaction conditions, high raw material conversion rate, high product yield, high product selectivity, and green environmental protection, and is suitable for large-scale industrial application. Attached Figure Description

[0028] Figure 1 The image shows the gas chromatogram of the organic phase separated in step 3) of Example 1. Detailed Implementation

[0029] The present invention will be further explained and described below with reference to specific embodiments.

[0030] The preparation method of amination-modified carbon nanotubes (N-CNTs) is as follows: 1g of carbon nanotubes (CNTs), 60mL of 98% H2SO4 solution and 20mL of 68% HNO3 solution are mixed and stirred under reflux at 40℃ in an oil bath for 4h. After filtration, the mixture is washed with water until neutral and dried. Then, 1g of the treated carbon nanotubes, 50mL of thionyl chloride, 2mL of pyridine and 5mL of N,N-dimethylformamide (DMF) are mixed and stirred under reflux at 70℃ in an oil bath for 12h. After filtration, the mixture is washed with water until neutral and dried. Then, 0.5g of the treated carbon nanotubes, 20mL of ethylenediamine and 3mL of triethylamine are mixed and stirred under nitrogen protection at 80℃ for 12h. After filtration, the mixture is washed with water until neutral and dried to obtain amination-modified carbon nanotubes.

[0031] The preparation methods for aminated graphene (NG) and aminated activated carbon (N-AC) are the same as those for aminated carbon nanotubes (N-CNTs).

[0032] Example 1: A method for synthesizing santalol, comprising the following steps: 1) Dissolve 1g of santalene in 30mL of dichloromethane, then add 0.96g of NBS, 0.02g of BPO and 0.02g of N-CNTs, and then reflux at 78°C under a nitrogen atmosphere for 8h. Then place it in an ice bath to cool to room temperature, and then add the reaction solution to 10mL of 5% NaHCO3 aqueous solution for washing. After standing, take the organic phase and rotary evaporate to obtain bromosantalene. 2) Dissolve bromosanthene and 1g of NaOAc in 40mL of ethyl acetate, then stir at 80℃ for 4h under a nitrogen atmosphere, cool to room temperature, add 50mL of ice water, add 50mL of diethyl ether, mix well, let stand, take the organic phase and rotary evaporate to obtain santhene acetate. 3) Dissolve santaloyl acetate in 15 mL of 50% methanol aqueous solution, then add 0.27 g of LiOH·H2O, stir at room temperature for 3 h, then add 50 mL of diethyl ether and mix well. Let stand, take the organic phase and rotary evaporate to obtain santalol.

[0033] According to the test results, the total yield of santalol in this embodiment was 98%.

[0034] Note: Take 1 mL of the organic phase separated in step 3) of this embodiment and analyze it using a gas chromatograph (GC). The obtained gas chromatogram is shown below. Figure 1 As shown, the total yield of santalol was then calculated using the internal standard method, with o-dichlorobenzene as the internal standard and dichloromethane and dodecane as solvents.

[0035] Example 2: A method for synthesizing santalol is identical to that in Example 1, except that “N-CNTs” in step 1) is replaced with “N-AC”.

[0036] According to the test results, the total yield of santalol in this embodiment was 68%.

[0037] Example 3: A method for synthesizing santalol is identical to that in Example 1, except that the "N-CNTs" in step 1) are replaced with "NG".

[0038] According to the test results, the total yield of santalol in this embodiment was 52%.

[0039] Example 4: A method for synthesizing santalol is identical to Example 1, except that the amount of NBS in step 1) is adjusted from "0.96g" to "0.5g", the amount of BPO in step 1) is adjusted from "0.02g" to "0.04g", and the step of "stirring and refluxing at 78°C for 8h" in step 1) is adjusted to "stirring and refluxing at 50°C for 4h".

[0040] According to the test results, the total yield of santalol in this embodiment was 64%.

[0041] Example 5: A method for synthesizing santalol is identical to Example 1, except that the amount of NBS in step 1) is adjusted from "0.96g" to "0.6g", the amount of N-CNTs in step 1) is adjusted from "0.02g" to "0.1g", and the substitution reaction temperature in step 1) is adjusted from "78℃" to "50℃".

[0042] According to the test, the total yield of santalol in this embodiment was 85%.

[0043] Example 6: A method for synthesizing santalol is identical to that in Example 1, except that the substitution reaction temperature in step 1) is changed from "78°C" to "90°C".

[0044] According to the test results, the total yield of santalol in this embodiment was 78%.

[0045] Example 7: A method for synthesizing santalol is identical to that in Example 1, except that the step 1) is changed from "stirring and refluxing at 78°C for 8 hours" to "stirring and refluxing at 80°C for 4 hours".

[0046] According to the test results, the total yield of santalol in this embodiment was 68%.

[0047] Example 8: A method for synthesizing santalol is identical to Example 1, except that the amount of NBS in step 1) is adjusted from "0.96g" to "1g" and the substitution reaction temperature in step 1) is adjusted from "78℃" to "50℃".

[0048] According to the test, the total yield of santalol in this embodiment was 97%.

[0049] Example 9: A method for synthesizing santalol is identical to Example 1, except that the amount of N-CNTs in step 1) is adjusted from "0.02g" to "0.05g" and the substitution reaction temperature in step 1) is adjusted from "78℃" to "70℃".

[0050] According to the test, the total yield of santalol in this embodiment was 85%.

[0051] Example 10: A method for synthesizing santalol is identical to that in Example 1, except that the step 1) is changed from "stirring and refluxing at 78°C for 8 hours" to "stirring and refluxing at 90°C for 6 hours".

[0052] According to the test, the total yield of santalol in this embodiment was 89%.

[0053] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A method for synthesizing santalol, characterized in that, Includes the following steps: 1) A substitution reaction was carried out by dispersing santalene, N-bromosuccinimide, benzoyl peroxide and aminated carbon material in an organic solvent to obtain bromosantalene; 2) Bromosanthene and sodium peracetate were dispersed in an organic solvent and subjected to an esterification reaction to obtain santhrenyl acetate; 3) The santaloyl acetate and lithium hydroxide monohydrate were dispersed in an aqueous methanol solution and hydrolyzed to obtain santalol.

2. The method for synthesizing santalol according to claim 1, characterized in that: In step 1), the mass ratio of santalene to aminated carbon material is 1:0.001 to 0.2; in step 1), the mass ratio of N-bromosuccinimide, benzoyl peroxide, and aminated carbon material is 1 to 100:0.1 to 2:

1.

3. The method for synthesizing santalol according to claim 1 or 2, characterized in that: Step 1) The aminated carbon material is at least one of aminated carbon nanotubes, aminated graphene, and aminated activated carbon.

4. The method for synthesizing santalol according to claim 1 or 2, characterized in that: Step 1) The amination of the carbon material is prepared by a method including the following steps: acid washing, water washing and drying of the carbon material, thionyl chloride and pyridine are dispersed in a solvent for reaction, the carbon material is separated for water washing and drying, the carbon material, ethylenediamine and triethylamine are mixed for reaction, and the carbon material is separated for water washing and drying.

5. The method for synthesizing santalol according to claim 1 or 2, characterized in that: The substitution reaction in step 1) is carried out at a temperature of 30℃ to 150℃ for a reaction time of 0.5h to 12h.

6. The method for synthesizing santalol according to claim 1, characterized in that: Step 2) The amount of sodium peracetate used is 100% to 300% of the mass of sandalwoodene.

7. The method for synthesizing santalol according to claim 1 or 6, characterized in that: Step 2) The esterification reaction is carried out at a temperature of 70℃~90℃ for a reaction time of 3h~7h.

8. The method for synthesizing santalol according to claim 1, characterized in that: Step 3) The amount of lithium hydroxide monohydrate used is 10% to 100% of the mass of santalene.

9. The method for synthesizing santalol according to claim 1 or 8, characterized in that: The hydrolysis reaction described in step 3) is carried out at room temperature for 2 to 5 hours.

10. The method for synthesizing santalol according to any one of claims 1, 2, 6 and 8, characterized in that: Step 1) The organic solvent is at least one of dichloromethane and dichloroethane; Step 2) The organic solvent is at least one of ethyl acetate and methyl acetate.

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