Method for synthesizing sandalwood ether from methoxycitronellene

Abstract

The invention discloses a method for synthesizing sandalwood ether from methoxy citronellene, which comprises the following steps: S1, under the catalytic action, carrying out Wacker oxidation reaction on the methoxy citronellene to obtain an acetyl intermediate; s2, the acetyl intermediate is subjected to a reduction reaction, and sandalwood ether is prepared. According to the method, methoxy citronellene which is low in price and easy to obtain serves as a raw material, C = C double bonds are converted into acetyl through Wacker oxidation, then the acetyl is reduced to obtain secondary alcohol, and therefore efficient and low-cost synthesis of sandalwood ether is achieved. The synthesis route is novel, secondary alcohol functional groups are introduced through Wacker oxidation and reduction reactions, compared with an epoxidation-hydrogenation method adopted in a traditional process, the byproduct methoxycitronellol is eliminated, and the total synthesis yield is remarkably increased.

Description

Technical Field

[0001] The invention relates to a method for synthesizing sandalwood ether, in particular to a method for synthesizing sandalwood ether from methoxycitronellene. Background Art

[0002] The fragrance of sandalwood has been widely loved by people everywhere since ancient times. Its fragrance was first discovered in sandalwood. Now the fragrance industry refers to this fresh, natural, mild and elegant woody fragrance as sandalwood, and spices with related fragrances are generally called sandalwood fragrances. With the development and progress of current analytical technology, chemists have determined that the main fragrance of sandalwood comes from α-santalol and β-santalol, and its structural formula is shown below.

[0003]

[0004] Not only does natural sandalwood grow very slowly, but the santalol content in the wood is very low, and the cost of naturally extracted santalol is very expensive. Furthermore, the chemical structure of santalol is relatively complex, and the cost of artificially synthesized santalol is not low. Taking the above two factors into consideration, flavors and fragrances have now developed a variety of santalol substitutes, such as sandalwood 208, sandalwood 210, polysantalol, santalol, etc. These substitutes have the characteristic aroma of sandalwood and are low in cost, which has promoted the promotion and application of sandalwood fragrances.

[0005] Among them, sandalwood ether is a new type of sandalwood discovered by Bush Boake Allen in 1973. It is the only linear sandalwood known so far. Sandalwood ether is a colorless and transparent liquid at room temperature. It has a fresh, elegant, delicate sandalwood aroma, as well as a certain floral scent. It has good permeability and is widely used in various daily chemical products such as soaps, cosmetics, and perfumes.

[0006] At present, the main synthesis route of sandalwood ether is as shown in the following formula. First, natural citronellene reacts with methanol under the action of an acid catalyst to obtain methoxycitronellene (CAS: 53767-86-5, 7-methoxy-3,7-dimethyl-1-octene), then an epoxidation reaction occurs to obtain an epoxide, and finally the epoxide is hydrogenated to obtain the sandalwood ether product. It is worth noting that there is a problem of chemical selectivity in the hydrogenation process of the epoxide, and a large amount of hydroxy-terminated methoxycitronellol will be produced as a byproduct. Although the raw material cost of this route is relatively low, it requires the consumption of an equivalent amount of peroxide, and there is a problem of regional selectivity in the last step of the hydrogenation reaction, so the route cost is relatively high, which limits the promotion and application of sandalwood ether.

[0007]

[0008] In summary, santal ether is a very good sandalwood fragrance with an elegant and delicate aroma. At present, the main synthesis route of this fragrance product is the citronellene epoxidation method, which has the disadvantages of a long synthesis route and poor chemical selectivity, resulting in a high cost of sandalwood and limiting the promotion and use of santal ether. In order to prepare santal ether products more economically and cheaply, it is urgent to develop a new synthesis route to improve the synthesis yield and reduce the production cost. Summary of the invention

[0009] In order to solve the above technical problems, the present invention proposes a method for synthesizing santal ether from methoxycitronellene. The method uses cheap and readily available methoxycitronellene as a raw material, converts the C=C double bond into an acetyl group through Wacker oxidation, and then reduces the acetyl group to obtain a secondary alcohol, thereby achieving efficient and low-cost synthesis of santal ether. The synthesis route of the present invention is novel, and a secondary alcohol functional group is introduced through Wacker oxidation and reduction reaction. Compared with the epoxidation-hydrogenation method used in the traditional process, the by-product methoxycitronellol is eliminated, and the total yield of the synthesis is significantly improved.

[0010] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0011] A method for synthesizing santal ether from methoxycitronellene comprises the following steps:

[0012]

[0013] S1, under the action of catalyst, methoxycitronellal undergoes Wacker oxidation reaction to obtain an acetyl intermediate;

[0014] S2. The acetyl intermediate undergoes a reduction reaction to obtain sandalwood ether.

[0015] As some examples of the present invention, the Wacker oxidation reaction in step S1 is synergistically catalyzed by a palladium catalyst and a copper catalyst;

[0016] Preferably, the palladium catalyst is selected from one or more of palladium chloride, palladium acetate, palladium bromide, palladium acetylacetonate, and sodium dichloropalladate;

[0017] Preferably, the copper catalyst is selected from one or more of copper chloride, copper acetate, copper bromide and copper iodide.

[0018] As some examples of the present invention, the amount of the palladium catalyst used is 0.05-2.0 mol% based on the molar amount of the raw material methoxycitronellene;

[0019] Preferably, the amount of the copper catalyst used is 0.5-3.0 mol % based on the molar amount of the copper catalyst relative to the raw material methoxycitronellene.

[0020] As some examples of the present invention, the Wacker oxidation reaction in step S1 is simultaneously carried out in the presence of an oxidant;

[0021] Preferably, the oxidant is selected from one or more of oxygen, air, oxygen-depleted air, hydrogen peroxide, tert-butyl peroxide, and phenylethanol peroxide.

[0022] As some examples of the present invention, the reaction time of the Wacker oxidation reaction in step S1 is 6-24 hours; and / or, the reaction temperature is 25-80° C.; and / or, the reaction pressure is 1-10 barG.

[0023] As some examples of the present invention, the reaction in step S1 is carried out in a solvent, and the solvent is selected from one or more of acetic acid, N,N-dimethylformamide, isopropanol, tert-butanol, N-methylpyrrolidone, acetonitrile, and water, preferably a mixture of water and at least one other solvent;

[0024] Preferably, the amount of solvent used in step S1 is 4.0-8.0 times the mass of the raw material methoxycitronellene.

[0025] As some examples of the present invention, step S2 uses catalytic hydrogenation and / or equivalent reducing agent reduction to perform a reduction reaction.

[0026] As some examples of the present invention, the catalytic hydrogenation method is carried out in the presence of a hydrogenation catalyst and an auxiliary agent;

[0027] Preferably, in the catalytic hydrogenation method, the hydrogenation catalyst is selected from one or more of Raney nickel, Raney cobalt, ruthenium carbon, iridium carbon, supported nickel, and supported copper catalysts; the carrier of the supported catalyst is selected from one or more of alumina, silicon oxide, activated carbon, and diatomaceous earth; more preferably, the amount of the hydrogenation catalyst is 0.5-5.0wt% of the mass of the acetyl intermediate;

[0028] Preferably, in the catalytic hydrogenation method, the auxiliary agent is selected from one or more of lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium carbonate, sodium methoxide, sodium ethoxide, and potassium ethoxide; more preferably, the amount of the auxiliary agent is 0.001-0.01 mol% of the molar amount of the acetyl intermediate;

[0029] Preferably, the reaction conditions of the catalytic hydrogenation method are: hydrogen pressure of 10.0-60.0 barG; and / or, reaction temperature of 60-120° C.; and / or, reaction time of 2-6 h.

[0030] As some examples of the present invention, the reducing agent used in the equivalent reducing agent reduction method is any one or more of lithium aluminum hydride, sodium borohydride, lithium borohydride, calcium borohydride, and diisobutylaluminum hydride;

[0031] Preferably, the amount of the reducing agent is 100-200 mol% of the molar amount of the acetyl intermediate;

[0032] Preferably, the reaction conditions of the equivalent reducing agent reduction method are: reaction time of 1-3 h; and / or, reaction temperature of 0-60° C.; and / or, reaction pressure of normal pressure.

[0033] As some examples of the present invention, the reduction reaction in step S2 is carried out in a solvent, and the solvent is selected from one or more of methanol, ethanol, n-propanol, isopropanol, tetrahydrofuran, 2-methyltetrahydrofuran, methyl tert-butyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, dichloromethane, dichloroethane, toluene, ethyl acetate, and n-butyl acetate;

[0034] Preferably, the amount of solvent used in step S2 is 4.0-8.0 times the mass of the acetyl intermediate.

[0035] The present invention adopts the above technical solution and has the following positive effects:

[0036] 1. The synthesis route used in this method is novel. Through the Wacker oxidation and reduction reaction, methoxycitronellol is converted into santalinol with high selectivity, eliminating the by-product of methoxycitronellol in the traditional process route, significantly improving the synthesis yield of the target product santalinol, and is expected to significantly reduce its production cost.

[0037] 2. The reduction reaction method is flexible, and can adopt high-pressure catalytic hydrogenation method or normal pressure equivalent reducing agent reduction method. The method is flexible and easy to operate. Both methods can synthesize sandalwood ether products with high yield and have good practical value. DETAILED DESCRIPTION

[0038] The present invention is further described below by means of specific examples. The examples described in the present invention are only used to illustrate the present invention and do not limit the scope of the present invention.

[0039] Unless otherwise specified, the raw materials and reagents in the following examples of the present invention can be obtained through conventional commercial routes.

[0040] The gas chromatography analysis conditions adopted in the present invention are as follows:

[0041] Instrument model: Agilent 7890B; Chromatographic column: Capillary column HP-3 (30m×0.30mm×0.25μm); Initial temperature 80℃, rise to 100℃ at a rate of 5℃ / min; then rise to 220℃ at a rate of 10℃ / min, and maintain for 5.0min. Carrier gas high-purity nitrogen, split ratio 30:1, split flow 42mL / min. Carrier gas saving: 19mL / min, start waiting time 5.0min. Injection temperature 250℃, detector FID, detector temperature 250℃, air flow 350mL / min, hydrogen flow 30mL / min, tail gas flow 60mL / min, injection volume 0.2μL.

[0042] [Example 1]

[0043] (1) Place a 500mL three-necked flask equipped with a magnetic stirrer in a normal temperature water bath at room temperature, add 161.8g (mass ratio 8:1) of a mixed solvent of N,N-dimethylformamide and water, methoxycitronellene (32.36g, 0.19mol) to the three-necked flask in turn, stir and mix evenly, then add palladium chloride (0.34g, 1.9mmol) and copper chloride (0.51g, 3.8mmol). After all materials are added, 1barG oxygen is introduced into the reaction solution through a submerged insertion tube at a ventilation rate of 12mL / min, and the tail gas is condensed through a condenser and discharged from the reaction system. During the reaction, the temperature is kept stable at 25°C and the reaction is carried out for 8 hours under rapid stirring. After sampling, the composition of the reaction solution is analyzed by GC, and the raw material methoxycitronellene disappears completely. The reaction solution was filtered with filter paper and the reaction solvent was removed by rotary evaporation. The crude product was then dissolved in ethyl acetate (150 mL), washed once with saturated aqueous sodium bicarbonate solution (20 mL) and saturated brine (20 mL), and the organic phase was dried over anhydrous sodium sulfate and distilled under reduced pressure to obtain 34.12 g of acetyl intermediate with a yield of 96.4%.

[0044] 1 H NMR (400MHz, CDCl3): δ3.32(s,3H),2.54(h,J=6.8Hz,1H),1.98(s,3H),1.54(q ,J=6.8Hz,2H),1.36(t,J=6.8Hz,2H),1.22-1,26(m,8H),1.11(d,J=6.8Hz,3H).

[0045] (2) At room temperature, first add a magnetic stirrer to a 250mL autoclave, then add 96.9g of methanol solvent, 24.22g (0.13mol) of acetyl intermediate, 0.12g of Raney nickel catalyst, and 0.6mg (0.001mmol) of sodium hydroxide additive in sequence. After all materials are added, seal the autoclave, replace nitrogen and hydrogen three times respectively, and then fill it with 60.0barG hydrogen. Put the autoclave in an oil bath, start stirring and heating, and raise the temperature in the autoclave to 100°C. During the reaction, keep the hydrogen pressure in the autoclave constant. After rapid stirring for 4 hours, take a sample and analyze the composition of the reaction liquid by gas chromatography. The results show that the conversion rate of the raw material acetyl intermediate is 99.5%, and the selectivity of the target product santalin ether is 99.1%.

[0046] 1 H NMR (400MHz, CDCl3): δ3.60(s,1H),3.38(p,J=6.8Hz,1H),3.30(s,3H),1.70-1,75(m,1H) ,1.38(t,J=6.8Hz,2H),1.21-1,26(m,10H),1.18(d,J=6.8Hz,3H),0.96(d,J=6.8Hz,3H).

[0047] [Example 2]

[0048] (1) Place a 500mL three-necked flask equipped with a magnetic stirrer in a normal temperature water bath at room temperature, add 170.3g (mass ratio 8:1) of a mixed solvent of N,N-dimethylformamide and water, methoxycitronellene (34.06g, 0.20mol) to the three-necked flask in turn, stir and mix evenly, then add palladium chloride (0.18g, 1.0mmol) and copper chloride (0.13g, 1.0mmol). After all materials are added, 1barG pure oxygen is introduced into the reaction solution through a submerged insertion tube at a ventilation rate of 12mL / min, and the tail gas is condensed through a condenser and discharged from the reaction system. During the reaction, the temperature is kept stable at 25°C, and the reaction is carried out for 10 hours under rapid stirring. After sampling, the composition of the reaction solution is analyzed by GC, and the raw material methoxycitronellene disappears completely. The reaction solution was filtered with filter paper and the reaction solvent was removed by rotary evaporation. The crude product was then dissolved in ethyl acetate (200 mL), washed once with saturated aqueous sodium bicarbonate solution (20 mL) and saturated brine (20 mL), and the organic phase was dried over anhydrous sodium sulfate and distilled under reduced pressure to obtain 36.89 g of acetyl intermediate with a yield of 99.0%.

[0049] (2) At room temperature, first add a magnetic stirrer to a 500mL autoclave, then add 193.7g of ethanol solvent, 26.08g (0.14mol) of acetyl intermediate, 1.3g of Raney nickel catalyst, and 0.8mg (0.0014mmol) of potassium hydroxide additive in sequence. After all materials are added, seal the autoclave, replace nitrogen and hydrogen three times respectively, and then fill it with 10barG hydrogen. Put the autoclave in an oil bath, start stirring and heating, and raise the temperature in the reactor to 60°C. During the reaction, keep the hydrogen pressure in the autoclave constant. After rapid stirring for 6 hours, take a sample and analyze the composition of the reaction liquid by gas chromatography. The results show that the conversion rate of the raw material acetyl intermediate is 99.3%, and the selectivity of the target product santalin ether is 99.4%.

[0050] [Example 3]

[0051] (1) Place a 500mL three-necked flask equipped with a magnetic stirrer in a normal temperature water bath at room temperature, add 149.9g (mass ratio 10:1) of a mixed solvent of N,N-dimethylformamide and water, methoxycitronellene (18.73g, 0.11mol) to the three-necked flask in turn, stir and mix evenly, then add palladium chloride (0.39g, 2.2mmol) and cuprous chloride (0.33g, 3.3mmol). After all materials are added, 1barG pure oxygen is introduced into the reaction solution through a submerged insertion tube at a ventilation rate of 24mL / min, and the tail gas is condensed through a condenser and discharged from the reaction system. During the reaction, the temperature is kept stable at 25°C, and the reaction is carried out for 6 hours under rapid stirring. After sampling, the composition of the reaction solution is analyzed by GC, and the raw material methoxycitronellene disappears completely. The reaction solution was filtered with filter paper and the reaction solvent was removed by rotary evaporation. The crude product was then dissolved in ethyl acetate (150 mL), washed once with saturated aqueous sodium bicarbonate solution (20 mL) and saturated brine (20 mL), and the organic phase was dried over anhydrous sodium sulfate and distilled under reduced pressure to obtain 20.16 g of acetyl intermediate with a yield of 98.4%.

[0052] (2) At room temperature, first add a magnetic stirrer to a 250mL autoclave, then add 102.5g of isopropanol solvent, 20.49g (0.11mol) of acetyl intermediate, 0.41g of Raney cobalt catalyst, and 3.6mg (0.0011mmol) of cesium carbonate auxiliary agent in sequence. After all materials are added, seal the autoclave, replace nitrogen and hydrogen three times respectively, and then fill it with 20barG hydrogen. Put the autoclave in an oil bath, start stirring and heating, and raise the temperature in the reactor to 120°C. Keep the hydrogen pressure in the autoclave unchanged during the reaction. After rapid stirring for 2 hours, take a sample and analyze the composition of the reaction liquid by gas chromatography. The results show that the conversion rate of the raw material acetyl intermediate is 99.3%, and the selectivity of the target product santalin ether is 99.2%.

[0053] [Example 4]

[0054] (1) Place a 500mL three-necked flask equipped with a magnetic stirrer in an oil bath at room temperature, add 149.9g (mass ratio 7:1) of a mixed solvent of N,N-dimethylformamide and water, methoxycitronellene (37.46g, 0.22mol) to the three-necked flask in turn, stir and mix evenly, then add palladium chloride (0.39g, 2.2mmol) and copper acetate (0.8g, 4.4mmol). After all materials are added, 5barG air is introduced into the reaction solution through a submerged insertion tube at a ventilation rate of 18mL / min, and the tail gas is condensed through a condenser and discharged from the reaction system. During the reaction, the temperature is kept stable at 50°C and the reaction is carried out for 12 hours under rapid stirring. After sampling, the composition of the reaction solution is analyzed by GC, and the raw material methoxycitronellene disappears completely. The reaction solution was filtered with filter paper and the reaction solvent N,N-dimethylformamide and water were removed by rotary evaporation. The crude product was then dissolved in ethyl acetate (200 mL), washed once with saturated aqueous sodium bicarbonate solution (20 mL) and saturated brine (20 mL), and the organic phase was dried over anhydrous sodium sulfate and distilled under reduced pressure to obtain 39.88 g of acetyl intermediate with a yield of 97.3%.

[0055] (2) At room temperature, first add a magnetic stirrer to a 250 mL autoclave, then add 111.8 g of methanol solvent, 27.94 g (0.15 mol) of 7-methoxy-3,7-dimethyl-2-octanone, 0.28 g of catalyst ruthenium carbon, and 0.4 mg (0.008 mmol) of auxiliary sodium methoxide in sequence. After all materials are added, seal the autoclave, replace nitrogen and hydrogen three times respectively, and then fill it with 30 barG hydrogen. Put the autoclave in an oil bath, start stirring and heating, and raise the temperature in the reactor to 80°C. During the reaction, keep the hydrogen pressure in the autoclave constant. After rapid stirring for 4 hours, take a sample and analyze the composition of the reaction liquid by gas chromatography. The results show that the conversion rate of the raw material acetyl intermediate is 99.5%, and the selectivity of the target product santalin ether is 99.5%.

[0056] [Example 5]

[0057] (1) Place a 500mL three-necked flask equipped with a magnetic stirrer in an oil bath at room temperature, add 153.3g (mass ratio 5:1) of a mixed solvent of acetic acid and water, methoxycitronellene (30.65g, 0.18mol) to the three-necked flask in turn, start stirring to mix the substrate and solvent evenly, and then add palladium acetate (0.20g, 0.9mmol) and copper chloride (0.48g, 3.6mmol). After all materials are added, 5barG air is introduced into the reaction solution through a submerged insertion tube at a ventilation rate of 20mL / min, and the tail gas is condensed through a condenser and discharged from the reaction system. During the reaction, the temperature is kept stable at 50°C and the reaction is carried out for 12 hours under rapid stirring. After sampling, the composition of the reaction solution is analyzed by GC, and the raw material methoxycitronellene disappears completely. The reaction solution was filtered with filter paper and the reaction solvent was removed by rotary evaporation. The crude product was then dissolved in ethyl acetate (200 mL), washed once with saturated aqueous sodium bicarbonate solution (20 mL) and saturated brine (20 mL), and the organic phase was dried over anhydrous sodium sulfate and distilled under reduced pressure to obtain 32.12 g of acetyl intermediate with a yield of 95.8%.

[0058] (2) Place a 500mL three-necked flask equipped with a magnetic stirrer in an ice-water bath at room temperature. After nitrogen replacement three times, add 96.87g of tetrahydrofuran solvent and 24.22g (0.13mol) of acetyl intermediate to the three-necked flask in turn, and start stirring to completely dissolve the intermediate. Then add 4.93g (0.13mol) of lithium aluminum hydride, a reducing reagent, in batches and slowly. During the addition process, bubbles are generated in the reaction liquid. The addition rate is controlled to prevent the reaction liquid from rushing. After all materials are added, keep the temperature of the reaction liquid stable at 0°C and continue the reaction for 1 hour under rapid stirring. Take a sample and analyze the composition of the reaction liquid by gas chromatography. The results show that the conversion rate of the raw material acetyl intermediate is 99.5%, and the selectivity of the target product santal ether is 98.1%.

[0059] [Example 6]

[0060] (1) Place a 500mL three-necked flask equipped with a magnetic stirrer in an oil bath at room temperature, add 153.3g (mass ratio 8:1) of a mixed solvent of acetonitrile and water, methoxycitronellene (30.65g, 0.18mol) to the three-necked flask in turn, stir and mix evenly, then add sodium dichloropalladate (0.26g, 0.9mmol) and copper chloride (0.48g, 3.6mmol). After all materials are added, 10barG 15% oxygen-depleted air is introduced into the reaction solution through a submerged insertion tube at a ventilation rate of 20mL / min, and the tail gas is condensed through a condenser and discharged from the reaction system. During the reaction, the temperature is kept stable at 80°C, and the reaction is carried out for 24 hours under rapid stirring. After sampling, the composition of the reaction solution is analyzed by GC, and the raw material methoxycitronellene disappears completely. The reaction solution was filtered with filter paper and the reaction solvent was removed by rotary evaporation. The crude product was then dissolved in ethyl acetate (200 mL), washed once with saturated aqueous sodium bicarbonate solution (20 mL) and saturated brine (20 mL), and the organic phase was dried over anhydrous sodium sulfate and distilled under reduced pressure to obtain 31.82 g of acetyl intermediate with a yield of 94.9%.

[0061] (2) Place a 500mL three-necked flask equipped with a magnetic stirrer in an ice-water bath at room temperature. After nitrogen replacement three times, add 193.74g of solvent ether and 24.22g (0.13mol) of acetyl intermediate to the three-necked flask in turn, and start stirring to completely dissolve the intermediate. Then add 9.87g (0.26mol) of reducing reagent lithium aluminum hydride in batches and slowly. During the addition process, bubbles are generated in the reaction liquid. Control the addition rate to prevent the reaction liquid from rushing. After all materials are added, keep the temperature of the reaction liquid stable at 0°C and continue the reaction for 3 hours under rapid stirring. Add excess methanol (10mL) to the reaction liquid to quench the reaction. Use gas chromatography to analyze the reaction conversion rate and selectivity. The results show that the conversion rate of the raw material acetyl intermediate is 99.6%, and the selectivity of the target product santalin ether is 99.2%.

[0062] [Example 7]

[0063] (1) Place a 500mL three-necked flask equipped with a magnetic stirrer in an oil bath at room temperature, add 178.8g (mass ratio 8:1) of a mixed solvent of N,N-methylpyrrolidone and water, methoxycitronellene (35.76g, 0.21mol) to the three-necked flask in turn, start stirring to mix the substrate and solvent evenly, and then add palladium chloride (0.15g, 0.8mmol) and copper chloride (0.28g, 2.1mmol). After all materials are added, 10barG 15% oxygen-depleted air is introduced into the reaction solution through a submerged insertion tube at a ventilation rate of 20mL / min, and the tail gas is condensed through a condenser and discharged from the reaction system. During the reaction, the temperature is kept stable at 80°C, and the reaction is carried out for 20 hours under rapid stirring. After sampling, the composition of the reaction solution is analyzed by GC, and the raw material methoxycitronellene disappears completely. The reaction solution was filtered with filter paper and the reaction solvent was removed by rotary evaporation. The crude product was then dissolved in ethyl acetate (200 mL), washed once with saturated aqueous sodium bicarbonate solution (20 mL) and saturated brine (20 mL), and the organic phase was dried over anhydrous sodium sulfate and distilled under reduced pressure to obtain 37.32 g of acetyl intermediate with a yield of 95.4%.

[0064] (2) Place a 500mL three-necked flask equipped with a magnetic stirrer in an oil bath at room temperature. After nitrogen replacement three times, add 145.31g of methyl tert-butyl ether and 24.22g (0.13mol) of the acetyl intermediate to the three-necked flask in turn, and start stirring to completely dissolve the intermediate. Then add 7.37g (0.19mol) of sodium borohydride, a reducing agent, in batches and slowly. During the addition process, bubbles are generated in the reaction solution. The addition rate is controlled to prevent the reaction solution from rushing. After all materials are added, the temperature of the reaction solution is kept stable at 60°C, and the reaction is continued for 3 hours under rapid stirring. Excess methanol (10mL) is added to the reaction solution to quench the reaction. The reaction conversion rate and selectivity are analyzed by gas chromatography. The results show that the conversion rate of the raw material acetyl intermediate is 99.4%, and the selectivity of the target product santalin ether is 99.3%.

[0065] The above is only a preferred embodiment of the present invention. It should be pointed out that ordinary technicians in this field can make several improvements and supplements without departing from the method of the present invention. These improvements and supplements should also be regarded as the scope of protection of the present invention.

Claims

1. A method for synthesizing santal ether from methoxycitronellene, characterized in that: The following steps are involved: S1, under the action of catalyst, methoxycitronellal undergoes Wacker oxidation reaction to obtain an acetyl intermediate; S2. The acetyl intermediate undergoes a reduction reaction to obtain sandalwood ether.

2. The method for synthesizing santal ether from methoxycitronellene according to claim 1, characterized in that: In step S1, the Wacker oxidation reaction is synergistically catalyzed by a palladium catalyst and a copper catalyst; Preferably, the palladium catalyst is selected from one or more of palladium chloride, palladium acetate, palladium bromide, palladium acetylacetonate, and sodium dichloropalladate; Preferably, the copper catalyst is selected from one or more of copper chloride, copper acetate, copper bromide and copper iodide.

3. The method for synthesizing santal ether from methoxycitronellene according to claim 2, characterized in that: The amount of the palladium catalyst used is 0.05-2.0 mol% based on the molar amount of the raw material methoxycitronellene; Preferably, the amount of the copper catalyst used is 0.5-3.0 mol % based on the molar amount of the copper catalyst relative to the raw material methoxycitronellene.

4. The method for synthesizing santal ether from methoxycitronellene according to any one of claims 1 to 3, characterized in that: The Wacker oxidation reaction in step S1 is carried out in the presence of an oxidant; Preferably, the oxidant is selected from one or more of oxygen, air, oxygen-depleted air, hydrogen peroxide, tert-butyl peroxide, and phenylethanol peroxide.

5. The method for synthesizing santal ether from methoxycitronellene according to any one of claims 1 to 4, characterized in that: The reaction time of the Wacker oxidation reaction in step S1 is 6-24 hours; and / or, the reaction temperature is 25-80° C.; and / or, the reaction pressure is 1.0-10 barG.

6. The method for synthesizing santal ether from methoxycitronellene according to any one of claims 1 to 5, characterized in that: The reaction in step S1 is carried out in a solvent, wherein the solvent is selected from one or more of acetic acid, N,N-dimethylformamide, isopropanol, tert-butanol, N-methylpyrrolidone, acetonitrile, and water, preferably a mixture of water and at least one other solvent; Preferably, the amount of solvent used in step S1 is 4.0-8.0 times the mass of the raw material methoxycitronellene.

7. The method for synthesizing santal ether from methoxycitronellene according to any one of claims 1 to 6, characterized in that: In step S2, a catalytic hydrogenation method and / or an equivalent reducing agent reduction method are used to perform a reduction reaction.

8. The method for synthesizing santal ether from methoxycitronellene according to claim 7, characterized in that: The catalytic hydrogenation method is carried out in the presence of a hydrogenation catalyst and an auxiliary agent; Preferably, in the catalytic hydrogenation method, the hydrogenation catalyst is selected from one or more of Raney nickel, Raney cobalt, ruthenium carbon, iridium carbon, supported nickel, and supported copper catalysts; the carrier of the supported catalyst is selected from one or more of alumina, silicon oxide, activated carbon, and diatomaceous earth; more preferably, the amount of the hydrogenation catalyst is 0.5-5.0wt% of the mass of the acetyl intermediate; Preferably, in the catalytic hydrogenation method, the auxiliary agent is selected from one or more of lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium carbonate, sodium methoxide, sodium ethoxide, and potassium ethoxide; more preferably, the amount of the auxiliary agent is 0.001-0.01 mol% of the molar amount of the acetyl intermediate; Preferably, the reaction conditions of the catalytic hydrogenation method are: hydrogen pressure of 10.0-60.0 barG; and / or, reaction temperature of 60-120° C.; and / or, reaction time of 2-6 h.

9. The method for synthesizing santal ether from methoxycitronellene according to claim 7, characterized in that: The reducing agent used in the equivalent reducing agent reduction method is any one or more of lithium aluminum hydride, sodium borohydride, lithium borohydride, calcium borohydride, and diisobutylaluminum hydride; Preferably, the amount of the reducing agent is 100-200 mol% of the molar amount of the acetyl intermediate; Preferably, the reaction conditions of the equivalent reducing agent reduction method are: reaction time of 1-3 h; and / or, reaction temperature of 0-60° C.; and / or, reaction pressure of normal pressure.

10. The method for synthesizing santal ether from methoxycitronellene according to any one of claims 1 to 9, characterized in that: The reduction reaction in step S2 is carried out in a solvent, and the solvent is selected from one or more of methanol, ethanol, n-propanol, isopropanol, tetrahydrofuran, 2-methyltetrahydrofuran, methyl tert-butyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, dichloromethane, dichloroethane, toluene, ethyl acetate, and n-butyl acetate; Preferably, the amount of solvent used in step S2 is 4.0-8.0 times the mass of the acetyl intermediate.

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