A method for synthesizing dehydrolinalool

Abstract

The application discloses a synthesis method of dehydro-linalool, and relates to the technical field of fine chemical engineering, which comprises the following steps: linalool is reacted with acetic anhydride to obtain acetyl-linalool; the acetyl-linalool is reacted with trichloroisocyanuric acid to obtain 2,6-dimethyl-3-chloro-6-acetyloxy-1,7-octadiene; the 2,6-dimethyl-3-chloro-6-acetyloxy-1,7-octadiene is reacted with lithium hydroxide under the action of aluminum phosphotungstate to obtain 2,6-dimethyl-6-acetyloxy-1,3(E),7-octatriene; the 2,6-dimethyl-6-acetyloxy-1,3(E),7-octatriene is reacted with a sodium hydroxide solution to obtain 2,6-dimethyl-1,3(E),7-trienyl-6-octanol; under the catalysis of SO4 2‑ / Fe2O3 and lipase Lipase AK, the 2,6-dimethyl-1,3(E),7-trienyl-6-octanol is reacted with p-chlorophenol acetate to obtain (R)-2,6-dimethyl-6-acetyloxy-1,3(E),7-octatriene; and the (R)-2,6-dimethyl-6-acetyloxy-1,3(E),7-octatriene is reacted with a sodium hydroxide solution to obtain dehydro-linalool. The application has the advantages of mild reaction condition, low cost and suitability for industrial production.

Description

Technical Field

[0001] This invention relates to the field of fine chemical engineering technology, and in particular to a method for synthesizing dehydrolinalool. Background Technology

[0002] (R)-2,6-Dimethyl-1,3(E),7-Trienyl-6-octanol, also known as dehydrolinalool, is a byproduct of natural linalool leaf oil, linalool oil, galangal oil, rosewood oil, coriander seed oil, magnolia leaf oil, lavender oil, bitter orange leaf oil, bergamot oil, sage oil, and numerous other flower oils. It possesses a strong floral aroma with spicy and lavender-like notes. It can be used in various daily chemical products, including food, beverages, surface cleaning products, fabric softeners, air fresheners, oral care products, and deodorants. It can also be used in the synthesis of ionones, vitamin A, vitamin K, and vitamin E.

[0003] The structural formula of dehydrolinalool:

[0004]

[0005] Dehydrolinalool is a high-grade fragrance, expensive, and its preparation methods are scarce. The only reported method in the literature is patent JP2004 / 107207A from Takasago Fragrance Industry Co., Ltd. of Japan.

[0006]

[0007] Starting with (R)-acetylinalool, the product is reacted with calcium hypochlorite to obtain a chlorinated derivative, which is then reacted with lithium bromide and lithium carbonate to obtain (R)-acetylinalool dehydrogenated. The acetyl group is then removed to yield the final product. This route requires a large quantity of expensive lithium reagent for the lithium reagent dehalogenation step. The reaction has poor reproducibility, making stable production difficult, and the yield is far lower than the 73% reported in the literature, resulting in high production costs. Summary of the Invention

[0008] To address the shortcomings of existing technologies, this invention provides a method for synthesizing dehydrolinalool, which is environmentally friendly, low-cost, and suitable for industrial production.

[0009] In order to achieve the objective of this invention, the following solution is proposed:

[0010] A method for synthesizing dehydrolinalool, the reaction formula is as follows:

[0011]

[0012] In the reaction formula, Ac2O is acetic anhydride, Pyr is pyridine, TCCA is trichloroisocyanuric acid, Cat is a catalyst, MeOH is methanol, Lipase AK is lipase AK, NaOH is sodium hydroxide, and LiOH is lithium hydroxide.

[0013] The specific steps are as follows:

[0014] Step 1: Using inexpensive linalool as the starting material, react it with an acetylation reagent to obtain acetylinalool. The acetylation reagent can be one of acetic anhydride, acetyl chloride, or p-chlorophenol acetate, etc. Acetic anhydride is preferred, and the amount of acetylation reagent used is 1.0~5.0 equivalents, with a preferred range of 1.1~1.8 equivalents.

[0015] The specific plan is as follows:

[0016] Dichloromethane, linalool, and pyridine were mixed, and the mixture was kept at 20℃-30℃. Acetic anhydride was added dropwise, and the mixture was stirred for 2 hours. The temperature was kept at 0℃-10℃, and the reaction system was slowly quenched by adding ice water. The mixture was separated, washed with water, sodium bicarbonate solution, and saturated brine, dried with sodium sulfate, filtered through a desiccant, and distilled under reduced pressure to obtain the crude product acetylinalool.

[0017] Step 2: Acetyllinalool reacts with a chlorine-containing oxidizing agent to yield 2,6-dimethyl-3-chloro-6-acetoxy-1,7-octadiene. The oxidizing agent can be one of the following: sodium hypochlorite, calcium hypochlorite, trichloroisocyanuric acid, sodium dichloroisocyanurate, disodium monochloroisocyanurate, or chlorine gas. Trichloroisocyanuric acid is preferred, and the amount of oxidizing agent used ranges from 0.5 to 2.0 equivalents, preferably from 0.5 to 1.0 equivalents.

[0018] The specific plan is as follows:

[0019] A mixture of dichloromethane and acetyllinalool was heated to 20℃-30℃, and an appropriate amount of glacial acetic acid was added. Trichloroisocyanuric acid was added in batches, and the reaction was maintained at this temperature for 6 hours. After the reaction was completed, the reaction system was filtered, the filter cake was washed, washed with water, dried, and desoluble. Finally, 2,6-dimethyl-3-chloro-6-acetoxy-1,7-octadiene was obtained by vacuum distillation.

[0020] Step 3: Under the action of an aluminum salt catalyst, 2,6-dimethyl-3-chloro-6-acetoxy-1,7-octadiene reacts with a base to yield 2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene. The catalyst can be one of aluminum phosphotungstenate, potassium aluminum sulfate, potassium aluminum tartrate, etc. Aluminum phosphotungstenate is preferred, with a dosage range of 1.0 wt% to 10.0 wt%, preferably 0.2 wt% to 0.5 wt%. The base can be one of sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate, lithium carbonate, etc. Lithium hydroxide is preferred, with a dosage range of 1.0 to 2.5 equivalents, preferably 1.0 to 1.5 equivalents.

[0021] The specific plan is as follows:

[0022] 2,6-Dimethyl-3-chloro-6-acetoxy-1,7-octadiene was dissolved in methanol, cooled to 0℃-5℃, aluminum phosphotungstate was added, lithium hydroxide was added, and the mixture was stirred at 0℃-5℃ for 3 hours. The reaction was then stopped, the system was filtered, the filter cake was washed, and the mixture was successively washed with water, extracted, washed with saturated sodium chloride solution, dried, and desolventized to obtain 2,6-dimethyl-6-acetoxy-1,3(E),7-octadiene.

[0023] Step 4: 2,6-Dimethyl-6-acetoxy-1,3(E),7-octtriene reacts with sodium hydroxide solution to give 2,6-dimethyl-1,3(E),7-trienyl-6-octanol. Specifically:

[0024] 2,6-Dimethyl-6-acetoxy-1,3(E),7-octtriene was added to a reaction flask with methanol. The mixture was cooled to 0°C, and 10% sodium hydroxide solution was added dropwise. The mixture was stirred at 0°C for 1 hour. The methanol was removed by concentration under reduced pressure, and dichloromethane was added for extraction. The mixture was separated, extracted, washed with saturated sodium chloride solution, dried, and desolventized. Finally, it was distilled under reduced pressure to obtain 2,6-dimethyl-1,3(E),7-trienyl-6-octanol.

[0025] Step 5: Under the catalysis of a solid superacid catalyst and lipase, 2,6-dimethyl-1,3(E),7-trienyl-6-octanol reacts with p-chlorophenol acetate to yield (R)-2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene. The solid superacid catalyst can be BF3 / Al2O3, Al2O3-SiO2, Y molecular sieve, or SO4. 2- Among Fe2O3, Amberlyst 15, and other options, SO4 is preferred. 2- The dosage of Fe2O3 solid superacid catalyst ranges from 5% to 50%, with 10% to 20% being preferred. The lipase catalyst can be one of Lipase AK, Lipase PS, or Novozym 435, with Lipase AK being preferred. The dosage of lipase ranges from 1% to 20%, with 3% to 10% being preferred.

[0026] The specific plan is as follows:

[0027] p-Chlorophenol acetate, toluene, lipase AK, and SO4 2-The mixture of Fe2O3 was cooled to 20℃-30℃, and 2,6-dimethyl-1,3(E),7-trienyl-6-octanol and toluene solution were added dropwise to the reaction system. After the addition was complete, the temperature was raised to 45℃ and the reaction was carried out for 12 hours. After the reaction was completed, the reaction system was filtered, the filter cake was washed, the filtrate was washed with water, washed with saturated sodium bicarbonate solution, dried, and desolventized. Finally, it was distilled under reduced pressure to obtain (R)-2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene.

[0028] Step 6: (R)-2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene reacts with sodium hydroxide solution to give dehydrolinalool, specifically:

[0029] (R)-2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene and methanol were added to a reaction flask. The mixture was cooled to 0°C, and 10% sodium hydroxide solution was added dropwise. The mixture was stirred at 0°C for 1 hour. The methanol was removed by concentration under reduced pressure, and dichloromethane was added for extraction. The mixture was separated, extracted, washed with saturated sodium chloride solution, dried, and desoluble. Finally, it was distilled under reduced pressure to obtain dehydrolinalool.

[0030] The highlights of this synthesis method are the third and fifth steps.

[0031] In the third step, a complex is formed between lithium hydroxide and aluminum phosphotungstenate, which allows for the removal of hydrogen halides under milder conditions and in higher yields to obtain double bonds. If aluminum phosphotungstenate is not used, and lithium hydroxide is used alone, the yield is low, and the following byproducts are generated:

[0032] and .

[0033] In the fifth step, Lipase AK demonstrated good applicability in ester synthesis, biofuel synthesis, and the synthesis of enantiomeric pure chiral drugs in the food industry. In this step, the racemic tertiary alcohol was converted to a single-configuration tertiary alcohol under the catalysis of Lipase AK. This tertiary alcohol was then subjected to the reaction of the superstrong solid acid SO42-. 2- Acetate is obtained through transesterification catalyzed by Fe₂O₃. Without Lipase AK catalysis, acetate with a single configuration cannot be obtained. The super-strong solid acid SO₄⁻ is not used. 2- The low conversion rate of Fe2O3 transesterification reaction leads to a low yield.

[0034] The advantages of this invention are that the synthetic route of this invention has mild reaction conditions, low cost, and is suitable for industrial production. Detailed Implementation

[0035] Linalool was purchased from Jiangxi Xinsen Natural Plant Oil Co., Ltd.

[0036] Lipase AK activity ≥20000 U / g, purchased from Sigma Aldrich.

[0037] Lipase PS activity ≥23000 U / g, purchased from Sigma Aldrich.

[0038] Super solid acid SO4 2- / Fe2O3 is homemade, and aluminum phosphotungstic acid is homemade.

[0039] A portion of the yield data in the comparative figure was obtained by recalculating the yield from GC detection data.

[0040] Example 1

[0041] Step 1: Synthesis of acetylinalool

[0042] In a 1000 mL three-necked flask, 308.6 mL of dichloromethane and 154.3 g (1.0 mol) of linalool were added and stirred until homogeneous. Then, 94.8 g (1.2 mol) of anhydrous pyridine was added. The mixture was kept at 20-30 °C. 112.3 g (1.1 mol) of acetic anhydride was slowly added dropwise to the reaction flask. After the addition was complete, the mixture was stirred for another 2 h and kept at 0-10 °C. The reaction system was then quenched by slowly adding 300 g of ice water. The mixture was separated, and 308.6 mL of extractant was added to the aqueous phase. The organic layers were combined and washed successively with 200 mL of water, sodium bicarbonate solution, and saturated brine. The mixture was dried over 20 g of anhydrous sodium sulfate, filtered through a desiccant, and distilled under reduced pressure to obtain 160.8 g of crude acetylinalool, with a yield of 82%.

[0043] Step 2: Synthesis of 2,6-dimethyl-3-chloro-6-acetoxy-1,7-octadiene

[0044] In a 1000ml three-necked flask, 450ml of dichloromethane and 150g (0.765mol) of acetyllinalool were added, along with 91.8g (1.53mol) of glacial acetic acid. The mixture was stirred and the temperature was controlled at 20℃-30℃. Trichloroisocyanuric acid (0.39mol) was added in batches, and the reaction was maintained at this temperature for 3 hours. After the reaction was completed, the temperature was controlled below 20℃, and the reaction system was quenched by adding dropwise to 200g of water. The mixture was separated, washed with 200g of saturated brine, dried with 50g of anhydrous sodium sulfate, filtered, and dissolved. Finally, 150.1g of 2,6-dimethyl-3-chloro-6-acetoxy-1,7-octadiene was obtained by vacuum distillation, with a yield of 85%.

[0045] Step 3: Synthesis of 2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene

[0046] 150 g (0.65 mol) of 2,6-dimethyl-3-chloro-6-acetoxy-1,7-octadiene was added to a 2000 mL three-necked flask, followed by 450 mL of methanol. The mixture was stirred and cooled to 0-5 °C. 3.0 g of aluminum phosphotungstate and 17.2 g (0.715 mol) of lithium hydroxide were added. The mixture was stirred at 0-5 °C for 3 h, and the reaction was stopped. The system was filtered, and the filter cake was washed successively with 100 mL of water, extracted with dichloromethane, washed with saturated sodium chloride solution, dried with 30 g of anhydrous sodium sulfate, filtered, and dissolved to obtain 104.8 g of 2,6-dimethyl-6-acetoxy-1,3(E),7-octadiene, with a yield of 83%.

[0047] Step 4: Synthesis of 2,6-dimethyl-1,3(E),7-trienyl-6-octanol

[0048] 103 g (0.53 mol) of 2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene was added to a 2000 mL three-necked flask, followed by 309 mL of methanol. The mixture was cooled to 0 °C, and 223 g (0.56 mol) of 10% sodium hydroxide solution was added dropwise. The mixture was stirred at 0 °C for 1 h. After the reaction was complete, the methanol was removed by concentration under reduced pressure at 30 °C-35 °C. The mixture was then extracted with 309 mL of dichloromethane. The layers were separated, and the extract was further extracted with 103 mL of dichloromethane. The organic layers were combined, washed with 103 g of saturated sodium chloride solution, dried with 20 g of anhydrous sodium sulfate, filtered, and dissolved. Finally, the mixture was distilled under reduced pressure to obtain 68.6 g of 2,6-dimethyl-1,3(E),7-trienyl-6-octanol, with a yield of 85%.

[0049] Step 5: Synthesis of (R)-2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene

[0050] Add 84.4 g (0.495 mol) of p-chlorophenol acetate to a 2000 mL three-necked flask, add 343 mL of toluene, add 3.4 g of lipase AK, and add 10 g of solid superacid SO4. 2- / Fe2O3, the mixture was cooled to 20℃-30℃, and 68.6g (0.45mol) of 2,6-dimethyl-1,3(E),7-trienyl-6-octanol and 34.3ml of toluene solution were added dropwise to the reaction system. After the addition was complete, the temperature was raised to 45℃ and the reaction was carried out for 12h. After the reaction was completed, the reaction system was filtered, the filter cake was washed, the filtrate was washed with 100g of water and 100g of saturated sodium bicarbonate solution, dried with 10g of anhydrous sodium sulfate, and the solvent was removed. Finally, the solution was distilled under reduced pressure to obtain (R)-2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene, 75.2g, with a yield of 86%.

[0051] Step 6: Synthesis of dehydrolinalool

[0052] 75.2 g (0.45 mol) of (R)-2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene was added to a 2000 mL three-necked flask, followed by 225 mL of methanol. The mixture was cooled to 0 °C, and 189 g (0.47 mol) of 10% sodium hydroxide solution was added dropwise. The mixture was stirred at 0 °C for 1 h. After the reaction was complete, the methanol was removed by concentration under reduced pressure at 30 °C-35 °C. The mixture was then extracted with 225 mL of dichloromethane. The layers were separated, and the extract was further extracted with 75 mL of dichloromethane. The organic layers were combined, washed with 75 g of saturated sodium chloride solution, dried with 10 g of anhydrous sodium sulfate, filtered, and dissolved. Finally, the mixture was distilled under reduced pressure to obtain 59.0 g of dehydrolinalool, 85%.

[0053] Comparative Example 1

[0054] Step 1: Synthesis of acetylinalool

[0055] In a 1000 mL three-necked flask, 308.6 mL of dichloromethane and 154.3 g (1.0 mol) of linalool were added and stirred until homogeneous. Then, 94.8 g (1.2 mol) of anhydrous pyridine was added, and the mixture was kept at -5°C to -5°C. 112.3 g (1.1 mol) of acetic anhydride was slowly added dropwise to the reaction flask. After the addition was complete, the mixture was stirred for another 2 h, and the temperature was kept at 0°C to -10°C. The reaction system was then slowly quenched in 300 g of ice water. The mixture was separated, and 308.6 mL of extractant was added to the aqueous phase. The organic layers were combined and washed successively with 200 mL of water, sodium bicarbonate solution, and saturated brine. The mixture was dried over 20 g of anhydrous sodium sulfate, filtered, and distilled under reduced pressure to obtain 110.2 g of crude acetylinalool, with a yield of 56.2%.

[0056] Step 2: Synthesis of 2,6-dimethyl-3-chloro-6-acetoxy-1,7-octadiene

[0057] 330 ml of dichloromethane and 110 g (0.562 mol) of acetylinalool were added to a 1000 ml three-necked flask. The mixture was stirred and the temperature was controlled at 20-30 °C. 66.4 g (0.286 mol) of trichloroisocyanuric acid was added in batches, and the reaction was continued for 3 h. After the reaction was completed, the temperature was controlled below 20 °C, and the reaction system was quenched by adding dropwise to 110 g of water. The mixture was separated, washed with 110 g of saturated brine, dried with 36 g of anhydrous sodium sulfate, filtered, and dissolved. Finally, 86.0 g of 2,6-dimethyl-3-chloro-6-acetoxy-1,7-octadiene was obtained by vacuum distillation, with a yield of 66.3%.

[0058] Step 3: Synthesis of 2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene

[0059] 75 g (0.33 mol) of 2,6-dimethyl-3-chloro-6-acetoxy-1,7-octadiene was added to a 2000 mL three-necked flask, followed by 225 mL of methanol. The mixture was stirred and cooled to 10 °C-25 °C, then 1.5 g of aluminum phosphotungstic acid and 8.6 g (0.358 mol) of lithium hydroxide were added. The mixture was stirred at 10 °C-25 °C for 3 h, and the reaction was stopped. The system was filtered, and the filter cake was washed successively with 100 mL of water, extracted with dichloromethane, washed with saturated sodium chloride solution, dried with 30 g of anhydrous sodium sulfate, filtered, and dissolved to obtain 39.8 g of 2,6-dimethyl-6-acetoxy-1,3(E),7-octadiene, with a yield of 63%.

[0060] Step 4: Synthesis of 2,6-dimethyl-1,3(E),7-trienyl-6-octanol

[0061] 34.3 g (0.177 mol) of 2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene was added to a 2000 mL three-necked flask, followed by 103 mL of methanol. The mixture was cooled to 10 °C, and 74.3 g (0.19 mol) of 10% sodium hydroxide solution was added dropwise. The mixture was stirred at 10 °C for 1 h. After the reaction was complete, the methanol was removed by concentration under reduced pressure at 30 °C-35 °C. The mixture was then extracted with 103 mL of dichloromethane. The layers were separated, and the organic layers were extracted again with 34.3 mL of dichloromethane. The organic layers were combined, washed with 34.3 g of saturated sodium chloride solution, dried with 10 g of anhydrous sodium sulfate, filtered, and dissolved. Finally, the mixture was distilled under reduced pressure to obtain 22.6 g of 2,6-dimethyl-1,3(E),7-trienyl-6-octanol, with a yield of 83%.

[0062] Step 5: Synthesis of (R)-2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene

[0063] Add 27.8 g (0.163 mol) of p-chlorophenol acetate, 113 ml of toluene, 1.1 g of lipase AK, and 3.3 g of solid superacid SO4 to a 2000 mL three-necked flask. 2- / Fe2O3, the mixture was cooled to 10℃-20℃, and 22.6g (0.147mol) of 2,6-dimethyl-1,3(E),7-trienyl-6-octanol and 11.3ml of toluene solution were added dropwise to the reaction system. After the addition was complete, the temperature was raised to 40℃ and the reaction was carried out for 12h. After the reaction was completed, the reaction system was filtered, the filter cake was washed, the filtrate was washed with 100g of water and 100g of saturated sodium bicarbonate solution, dried with 10g of anhydrous sodium sulfate, and the solvent was removed. Finally, the solution was distilled under reduced pressure to obtain (R)-2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene, 23.3g, with a yield of 82%.

[0064] Step 6: Synthesis of dehydrolinalool

[0065] 23.3 g (0.12 mol) of (R)-2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene was added to a 2000 mL three-necked flask, followed by 70 mL of methanol. The mixture was cooled to 10 °C, and 58.8 g (0.146 mol) of 10% sodium hydroxide solution was added dropwise. The mixture was stirred at 10 °C for 1 h. After the reaction was complete, the methanol was removed by concentration under reduced pressure at 30 °C-35 °C. The mixture was then extracted with 70 mL of dichloromethane, separated, and extracted again with 23.3 mL of dichloromethane. The organic layers were combined, washed with 23.3 g of saturated sodium chloride solution, dried with 3.1 g of anhydrous sodium sulfate, filtered, dissolved, and finally distilled under reduced pressure to obtain 14.8 g of dehydrolinalool, with a yield of 80%.

[0066] Comparative Example 2

[0067] Step 1: Synthesis of acetylinalool

[0068] In a 1000 mL three-necked flask, 308.6 mL of dichloromethane and 154.3 g (1.0 mol) of linalool were added and stirred until homogeneous. Then, 94.8 g (1.2 mol) of anhydrous pyridine was added. At 10℃-20℃, 112.3 g (1.1 mol) of acetic anhydride was slowly added dropwise to the reaction flask. After the addition was complete, the reaction was stirred for another 2 h. The temperature was controlled at 0℃-10℃. The reaction system was then slowly quenched by adding 300 g of ice water. The mixture was separated, and 308.6 mL of extractant was added to the aqueous phase. The organic layers were combined and washed successively with 200 mL of water, sodium bicarbonate solution, and saturated brine. The mixture was dried over 20 g of anhydrous sodium sulfate, filtered, and distilled under reduced pressure to obtain crude acetylinalool, 149.1 g, with a yield of 76%.

[0069] Step 2: Synthesis of 2,6-dimethyl-3-chloro-6-acetoxy-1,7-octadiene

[0070] In a 1000ml three-necked flask, 330ml of dichloromethane and 110g (0.56mol) of acetyllinalool were added, followed by stirring. The temperature was controlled at 20℃-30℃, and 66.4g (0.286mol) of trichloroisocyanuric acid was added in batches. The reaction was continued for 3 hours. After the reaction was completed, the temperature was controlled below 20℃, and the reaction system was quenched by adding 110g of water dropwise. The mixture was separated, washed with 110g of saturated brine, dried with 36g of anhydrous sodium sulfate, filtered, and dissolved. Finally, 2,6-dimethyl-3-chloro-6-acetoxy-1,7-octadiene was obtained by vacuum distillation, yielding 98.7g, with a yield of 76.3%.

[0071] Step 3: Synthesis of 2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene

[0072] 97.0 g (0.42 mol) of 2,6-dimethyl-3-chloro-6-acetoxy-1,7-octadiene was added to a 2000 mL three-necked flask, followed by 291 mL of methanol. The mixture was stirred and cooled to 0-5 °C. 17.2 g (0.715 mol) of lithium hydroxide was added, and the mixture was stirred at 0-5 °C for 3 h. The reaction was then stopped, and the system was filtered. The filter cake was washed with 100 mL of water, extracted with dichloromethane, washed with saturated sodium chloride solution, dried with 30 g of anhydrous sodium sulfate, filtered, and dissolved to obtain 39.2 g of 2,6-dimethyl-6-acetoxy-1,3(E),7-octadiene, with a yield of 48%.

[0073] Step 4: Synthesis of 2,6-dimethyl-1,3(E),7-trienyl-6-octanol

[0074] 34.3 g (0.177 mol) of 2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene was added to a 2000 mL three-necked flask, followed by 103 mL of methanol. The mixture was kept at 30 °C, and 74.3 g (0.19 mol) of 10% sodium hydroxide solution was added dropwise. The mixture was stirred at 30 °C for 1 h. After the reaction was complete, the methanol was removed by vacuum concentration at 30 °C-35 °C. The mixture was then extracted with 103 mL of dichloromethane. The layers were separated, and the organic layers were extracted again with 34.3 mL of dichloromethane. The organic layers were combined, washed with 34.3 g of saturated sodium chloride solution, dried with 10 g of anhydrous sodium sulfate, filtered, and dissolved. Finally, the mixture was distilled under reduced pressure to obtain 11.7 g of 2,6-dimethyl-1,3(E),7-trienyl-6-octanol, with a yield of 43%.

[0075] Step 5: Synthesis of (R)-2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene

[0076] Add 14.3 g (0.084 mol) of p-chlorophenol acetate, 58.5 ml of toluene, 0.6 g of lipase AK, and 0.5 g of solid superacid SO4 to a 2000 mL three-necked flask. 2- Fe2O3 was used to cool the mixture to 10℃-20℃. 11.7g (0.076mol) of 2,6-dimethyl-1,3(E),7-trienyl-6-octanol and 11.3ml of toluene solution were added dropwise to the reaction system. After the addition was complete, the temperature was raised to 40℃ and the reaction was carried out for 12h. After the reaction was completed, the reaction system was filtered, the filter cake was washed, the filtrate was washed with 50g of water and 50g of saturated sodium bicarbonate solution, dried with 5g of anhydrous sodium sulfate, and the solvent was removed. Finally, the solution was distilled under reduced pressure to obtain 15.3g of crude (R)-2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene. The GC external standard for the crude product contained 6.6g of (R)-2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene, with a yield of 44.9%.

[0077] Step 6: Synthesis of dehydrolinalool

[0078] 6 g (0.031 mol) of (R)-2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene was added to a 2000 mL three-necked flask, followed by 20 mL of methanol. The mixture was cooled to 30 °C, and 13 g (0.032 mol) of 10% sodium hydroxide solution was added dropwise. The mixture was stirred at 30 °C for 1 h. After the reaction was complete, the methanol was removed by concentration under reduced pressure at 30 °C-35 °C. The mixture was then extracted with 20 mL of dichloromethane. The layers were separated, and the organic layers were extracted again with 20 mL of dichloromethane. The organic layers were combined, washed with 20 g of saturated sodium chloride solution, dried with 5 g of anhydrous sodium sulfate, filtered, and dissolved. Finally, the mixture was distilled under reduced pressure to obtain 3.0 g of dehydrolinalool, with a yield of 63.0%.

[0079] Comparative Example 3

[0080] Step 1: Synthesis of acetylinalool

[0081] In a 1000 mL three-necked flask, 308.6 mL of dichloromethane and 154.3 g (1.0 mol) of linalool were added and stirred until homogeneous. Then, 94.8 g (1.2 mol) of anhydrous pyridine was added, and the mixture was kept at 30-40 °C. 112.3 g (1.1 mol) of acetic anhydride was slowly added dropwise to the reaction flask. After the addition was complete, the mixture was stirred for another 2 h, and the temperature was kept at 0-10 °C. The reaction system was then slowly quenched in 300 g of ice water. The mixture was separated, and 308.6 mL of extractant was added to the aqueous phase. The organic layers were combined and washed successively with 200 mL of water, sodium bicarbonate solution, and saturated brine. The mixture was dried over 20 g of anhydrous sodium sulfate, filtered, and distilled under reduced pressure to obtain 129.6 g of crude acetylinalool, with a yield of 65.3%.

[0082] Step 2: Synthesis of 2,6-dimethyl-3-chloro-6-acetoxy-1,7-octadiene

[0083] In a 1000ml three-necked flask, 330ml of dichloromethane and 110g (0.56mol) of acetylinalool were added, along with 69.2g (1.12mol) of boric acid. The mixture was stirred and the temperature was controlled at 20℃-30℃. Trichloroisocyanuric acid (0.286mol) was added in batches, and the reaction was continued for 3 hours. After the reaction was completed, the mixture was filtered at a temperature below 20℃. The filter cake was washed with 110ml of dichloromethane, and the filtrate was quenched by adding dropwise to 110g of water. The mixture was separated, washed with 110g of saturated brine, and the organic layer was dried with 36g of anhydrous sodium sulfate. The mixture was filtered, dissolved, and finally distilled under reduced pressure to obtain 106.1g of 2,6-dimethyl-3-chloro-6-acetoxy-1,7-octadiene, with a yield of 82.0%.

[0084] Step 3: Synthesis of 2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene

[0085] 97.0 g (0.42 mol) of 2,6-dimethyl-3-chloro-6-acetoxy-1,7-octadiene was added to a 2000 mL three-necked flask, followed by 291 mL of methanol. The mixture was stirred and cooled to 0-5 °C, then 1.5 g of aluminum phosphotungstic acid and 28.6 g (0.715 mol) of sodium hydroxide were added. The mixture was stirred at 0-5 °C for 3 h, and the reaction was stopped. The system was filtered, and the filter cake was washed successively with 100 mL of water, extracted with dichloromethane, washed with saturated sodium chloride solution, dried with 30 g of anhydrous sodium sulfate, filtered, and dissolved to obtain 84.22 g of crude 2,6-dimethyl-6-acetoxy-1,3(E),7-octadiene. The GC external standard contained 11.9 g of 2,6-dimethyl-6-acetoxy-1,3(E),7-octadiene, with a yield of 14.6%.

[0086] Step 4: Synthesis of 2,6-dimethyl-1,3(E),7-trienyl-6-octanol

[0087] 34.3 g (0.177 mol) of 2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene was added to a 2000 mL three-necked flask, followed by 103 mL of methanol. The mixture was kept at 30 °C, and 74.3 g (0.19 mol) of 10% sodium hydroxide solution was added dropwise. The mixture was stirred at 30 °C for 1 h. After the reaction was complete, the methanol was removed by vacuum concentration at 30 °C-35 °C. The mixture was then extracted with 103 mL of dichloromethane. The layers were separated, and the organic layers were extracted again with 34.3 mL of dichloromethane. The organic layers were combined, washed with 34.3 g of saturated sodium chloride solution, dried with 10 g of anhydrous sodium sulfate, filtered, and dissolved. Finally, the mixture was distilled under reduced pressure to obtain 11.7 g of 2,6-dimethyl-1,3(E),7-trienyl-6-octanol, with a yield of 43%.

[0088] Step 5: Synthesis of (R)-2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene

[0089] Add 14.3 g (0.084 mol) of p-chlorophenol acetate, 58.5 ml of toluene, 0.6 g of lipase PS, and 1.5 g of solid superacid SO4 to a 2000 mL three-necked flask. 2-Fe2O3 was used to cool the mixture to 10℃-20℃. 11.7 g (0.076 mol) of 2,6-dimethyl-1,3(E),7-trienyl-6-octanol and 11.3 ml of toluene solution were added dropwise to the reaction system. After the addition was complete, the temperature was raised to 40℃ and the reaction was carried out for 12 h. After the reaction was completed, the reaction system was filtered, the filter cake was washed, the filtrate was washed with 50 g of water and 50 g of saturated sodium bicarbonate solution, dried with 5 g of anhydrous sodium sulfate, and the solvent was removed. Finally, the solution was distilled under reduced pressure to obtain 11.6 g of (R)-2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene, with a yield of 79.1%.

[0090] Step 6: Synthesis of dehydrolinalool

[0091] 6 g (0.031 mol) of (R)-2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene was added to a 2000 mL three-necked flask, followed by 20 mL of methanol. The mixture was cooled to 30 °C, and 26 g (0.032 mol) of 5% sodium hydroxide solution was added dropwise. The mixture was stirred at 30 °C for 1 h. After the reaction was complete, the methanol was removed by concentration under reduced pressure at 30 °C-35 °C. The mixture was then extracted with 20 mL of dichloromethane. The layers were separated, and the organic layers were extracted again with 20 mL of dichloromethane. The organic layers were combined, washed with 20 g of saturated sodium chloride solution, dried with 5 g of anhydrous sodium sulfate, filtered, and dissolved. Finally, the mixture was distilled under reduced pressure to obtain 3.5 g of dehydrolinalool, with a yield of 74.0%.

[0092] Among them, regarding the catalyst SO4 2- The preparation method of Fe2O3 is as follows:

[0093] Weigh 50g of ferrous sulfate heptahydrate powder into a crucible, spread it evenly, place it in a muffle furnace, heat it to 550℃ using a program, maintain the temperature for 5 hours, cool it down to 100℃, and then transfer it to a desiccator to cool to room temperature for later use.

[0094] The preparation method of the catalyst aluminum phosphotungstic acid is as follows:

[0095] A 0.1 mol / L aqueous solution of aluminum nitrate was added dropwise to a 0.1 mol / L solution of phosphotungstic acid while stirring. After the addition was complete, the reaction was allowed to proceed for 0.5 h. The solution was then concentrated under reduced pressure at 80 °C to remove moisture, resulting in a white solid. The solid was then ground into powder and dried in a muffle furnace at 400 °C for 8 h. The powder was then removed at 120 °C and placed in a desiccator to cool to room temperature for later use.

[0096] The above embodiments are only used to illustrate the technical concept and features of the present invention, and are not intended to be unique or to limit the present invention. Those skilled in the art should understand that various changes or equivalent substitutions made to the present invention without departing from its scope are all within the protection scope of the present invention.

Claims

1. A method for synthesizing dehydrolinalool, characterized in that, Includes the following steps: Step 1: Linalool is used as a starting material and reacts with acetic anhydride to obtain acetylinalool; Step 2: Acetyllinalool reacts with trichloroisocyanuric acid to give 2,6-dimethyl-3-chloro-6-acetoxy-1,7-octadiene; Step 3: Under the action of aluminum phosphotungstic acid catalyst, 2,6-dimethyl-3-chloro-6-acetoxy-1,7-octadiene reacts with lithium hydroxide to obtain 2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene. Step 4: 2,6-Dimethyl-6-acetoxy-1,3(E),7-octtriene reacts with sodium hydroxide solution to give 2,6-dimethyl-1,3(E),7-trienyl-6-octanol; Step 5: In the catalyst SO4 2- Under the catalysis of Fe2O3 and lipase Lipase AK, 2,6-dimethyl-1,3(E),7-trienyl-6-octanol reacts with p-chlorophenol acetate to give (R)-2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene. Step 6: (R)-2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene reacts with sodium hydroxide solution to give dehydrolinalool.

2. The method for synthesizing dehydrolinalool according to claim 1, characterized in that, The first step is as follows: Dichloromethane, linalool, and pyridine are mixed, and the mixture is kept at a temperature of 20℃-30℃. Acetic anhydride is added dropwise, and the mixture is stirred for 2 hours. The temperature is kept at 0℃-10℃, and the reaction system is slowly added to ice water to quench it. The mixture is separated, washed with water, sodium bicarbonate solution, and saturated brine, dried with sodium sulfate, filtered through a desiccant, and distilled under reduced pressure to obtain the crude product acetylinalool.

3. The method for synthesizing dehydrolinalool according to claim 1, characterized in that, The second step is as follows: The mixture of dichloromethane and acetyllinalool is heated to 20℃-30℃, an appropriate amount of glacial acetic acid is added, and trichloroisocyanuric acid is added in batches. The reaction is kept at this temperature for 3 hours. After the reaction is completed, the reaction system is filtered, the filter cake is washed, washed with water, dried, and desoluble. Finally, it is distilled under reduced pressure to obtain 2,6-dimethyl-3-chloro-6-acetoxy-1,7-octadiene.

4. The method for synthesizing dehydrolinalool according to claim 1, characterized in that, The third step is as follows: Dissolve 2,6-dimethyl-3-chloro-6-acetoxy-1,7-octadiene in methanol, cool to 0℃-5℃, add aluminum phosphotungstate and lithium hydroxide, stir at 0℃-5℃ for 3 hours, stop the reaction, filter the system, wash the filter cake, and then wash with water, extract, wash with saturated sodium chloride solution, dry, and remove solvent to obtain 2,6-dimethyl-6-acetoxy-1,3(E),7-octadiene.

5. The method for synthesizing dehydrolinalool according to claim 1, characterized in that, The fourth step is as follows: 2,6-Dimethyl-6-acetoxy-1,3(E),7-octtriene and methanol are added to a reaction flask, the mixture is cooled to 0°C, 10% sodium hydroxide solution is added dropwise, and the reaction is continued to be stirred at 0°C for 1 hour. The methanol is removed by concentration under reduced pressure, and dichloromethane is added for extraction. After separation, extraction, washing with saturated sodium chloride solution, drying, and solvent removal, 2,6-dimethyl-1,3(E),7-trienyl-6-octanol is obtained by distillation under reduced pressure.

6. The method for synthesizing dehydrolinalool according to claim 1, characterized in that, The fifth step involves: adding p-chlorophenol acetate, toluene, lipase AK, and SO4. 2- The mixture of Fe2O3 was cooled to 20℃-30℃, and 2,6-dimethyl-1,3(E),7-trienyl-6-octanol and toluene solution were added dropwise to the reaction system. After the addition was complete, the temperature was raised to 45℃ and the reaction was carried out for 12 hours. After the reaction was completed, the reaction system was filtered, the filter cake was washed, the filtrate was washed with water, washed with saturated sodium bicarbonate solution, dried, and desolventized. Finally, it was distilled under reduced pressure to obtain (R)-2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene.

7. The method for synthesizing dehydrolinalool according to claim 1, characterized in that, The sixth step is as follows: (R)-2,6-dimethyl-6-acetoxy-1,3(E),7-octtriene and methanol are added to a reaction flask, the mixture is cooled to 0°C, 10% sodium hydroxide solution is added dropwise, the reaction is continued to be stirred at 0°C for 1 hour, methanol is removed by vacuum concentration, dichloromethane is added for extraction, and after separation, extraction, washing with saturated sodium chloride solution, drying, solvent removal, and finally vacuum distillation, dehydrolinalool is obtained.

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