Synthesis method of high-purity homomyrcene

Abstract

The invention provides a synthesis method of high-purity homomyrcene, which comprises the following steps: carrying out [2 + 2] cycloaddition reaction on 8-methyl-2, 7-nonadien-4-ketone and ketene to obtain a beta-lactone intermediate, and carrying out reverse cycloaddition reaction on the beta-lactone intermediate to obtain a high-purity homomyrcene product. According to the present invention, the synthesis route is novel and short, the simple and easily available 8-methyl-2, 7-nonadien-4-one and the ketene are adopted as the raw materials, the homomyrcene is simply, conveniently and efficiently prepared through the cycloaddition and ring opening two-step reaction, the overall yield of the route is high, and compared with the Grignard addition-dehydration method adopted by the traditional process, the content of the target isomer is significantly increased, and the yield of the homomyrcene is significantly improved; the development of high myrcene downstream derivatives is convenient.

Description

Technical Field

[0001] The invention belongs to the field of fine chemicals and flavors and fragrances, and particularly relates to a method for synthesizing high-purity homomyrcene. Background Art

[0002] Georgywood was invented and discovered by Givaudan. Its molecular structure is shown below. It is a mixture of a pair of isomers, and the main fragrance comes from isomer 1. Georgywood is a synthetic fragrance, similar to ambergris, with elegant amber and woody fragrances. The fragrance is pure, fresh, and slightly sweet with green mint. It is often used by Givaudan perfumers in their fragrance blending to create woody fragrances.

[0003]

[0004] The synthesis of Georges wood is usually based on homomyrcene as a raw material, and 3-methyl 3-butene-2-one undergoes DA addition reaction, and then the homomyrcene is obtained under acidic conditions. Homomyrcene can be obtained by methyl Grignard reagent and citral addition and dehydration. The homomyrcene obtained by this method is generally a mixture of three isomers 5, 6, and 7. In order to obtain a relatively pure intermediate 8, isomer 6 needs to be separated and removed first to obtain a mixture of isomers 5 and 7. The mixture is then subjected to DA reaction with 3-methyl 3-butene-2-one. Since the reaction activity of 5 is higher than that of 7, a relatively pure intermediate 8 can be obtained. Due to the presence of isomers 6 and 7, the yield of this synthetic route is relatively low. It is calculated that 80% of intermediate 4 is converted into by-products (Chimia, 2006, 60, 574-579). There are also some other synthetic routes reported for Georges-Salt. For example, in 2009, Givaudan reported that Georges-Salt was obtained from homomyrcene and methacrylonitrile through DA addition, cyclization, Grignard addition, etc. The yield was much higher than that of the previous routes. Isomer 5 is still an indispensable raw material (Tetrahydron, 2009, 65, 10495-10505).

[0005]

[0006] In summary, George's wood fragrance is a very good woody and amber fragrance with an elegant and delicate aroma. It is widely used in high-end flavors and perfumes. At present, the main synthesis route of this product is to use homomyrcene as a raw material, and obtain it through DA addition, cyclization and other reactions. Among them, homomyrcene is the key raw material for synthesizing George's wood fragrance. Since the current homomyrcene synthesis method usually obtains a mixture of three isomers, only one isomer is a useful intermediate, thus increasing the content of the key raw material homomyrcene useful intermediate and reducing its synthesis cost can make George's wood fragrance products more economical and cheap. Summary of the invention

[0007] The object of the present invention is to provide a method for synthesizing homomyrcene in a simple and efficient manner using 8-methyl-2,7-nonadien-4-one and vinyl ketone as raw materials. The two raw materials are first subjected to a [2+2] cycloaddition reaction to obtain a β-lactone intermediate, and the intermediate undergoes a reverse cycloaddition reaction to release a molecule of carbon dioxide, thereby obtaining a high-purity homomyrcene product.

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

[0009] A method for synthesizing high-purity homomyrcene comprises the following steps:

[0010] 1) 8-methyl-2,7-nonadien-4-one and vinyl ketone undergo a [2+2] cycloaddition reaction in the presence of a catalyst to obtain a β-lactone intermediate;

[0011] 2) The β-propiolactone intermediate undergoes a reverse cycloaddition reaction to release a molecule of CO 2 , to obtain high-purity homomyrcene.

[0012] The synthesis route of homomyrcene described in the present invention is schematically shown as follows:

[0013]

[0014] In the present invention, the catalyst in step 1) is a Lewis acid catalyst, preferably one or more of boron trifluoride etherate, boron trifluoride acetic acid, zinc chloride, zinc bromide, zinc acetate, zinc acetylacetonate, ferric chloride, aluminum chloride, scandium trifluoromethanesulfonate, and yttrium trifluoromethanesulfonate; and

[0015] Preferably, the amount of the catalyst in step 1) is 0.2-3.0% of the molar amount of 8-methyl-2,7-nonadien-4-one, such as 0.5%, 1.0%, 1.5%, 2.0%, 2.5%, 3.0%, etc.;

[0016] More preferably, in step 1), the molar ratio of 8-methyl-2,7-nonadien-4-one to ketene is 1.0:1.1 to 1.5, such as 1:1.1, 1:1.2, 1:1.3, 1:1.4, etc.

[0017] In the present invention, the [2+2] cycloaddition reaction in step 1) is carried out under solvent conditions;

[0018] Preferably, the solvent is selected from one or more polar or non-polar aprotic solvents, preferably one or more of toluene, ether, methyl tert-butyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, methyl acetate, ethyl acetate, butyl acetate, ethyl butyrate, dichloromethane, chloroform, and dichloroethane;

[0019] More preferably, the amount of the solvent used is 3.0 to 5.0 times the mass of 8-methyl-2,7-nonadien-4-one, for example, 3.5 times, 4 times, 4.5 times, etc.

[0020] In the present invention, in the [2+2] cycloaddition reaction in step 1), the reaction temperature is 0 to 40°C, for example, 5°C, 10°C, 15°C, 20°C, 25°C, 30°C, 35°C, 40°C, etc.; the reaction time is 3 to 6h, for example, 4h, 5h, etc.; the reaction time is calculated from the start of ketene feeding.

[0021] Preferably, the [2+2] cycloaddition reaction adopts a semi-continuous process, 8-methyl-2,7-nonadien-4-one, solvent and catalyst are added at one time, and ketene is continuously added to the above mixed solution.

[0022] In the present invention, after the [2+2] cycloaddition reaction in step 1) is completed, a terminator is added to quench the reaction;

[0023] Preferably, the terminator is an inorganic weak base, preferably one or more of sodium bicarbonate, potassium bicarbonate, sodium carbonate, potassium carbonate, potassium monohydrogen phosphate, ammonium phosphate, diammonium hydrogen phosphate, and lithium carbonate;

[0024] Preferably, the amount of the terminator is 100-120% of the molar amount of the catalyst, such as 105%, 110%, 115%, etc.

[0025] In the present invention, the reverse cycloaddition reaction in step 2) is carried out in a reactive distillation tower, and the β-lactone intermediate is continuously fed into the bottom of the tower and undergoes a reverse cycloaddition reaction to generate products such as homomyrcene and CO 2 , both are vaporized and evaporated and extracted from the top of the tower.

[0026] In the present invention, in step 2), a solvent is added to the bottom of the reactive distillation tower;

[0027] Preferably, the solvent may be any one of, but not limited to, dimethyl phthalate, diethyl phthalate, dipropyl phthalate, diisopropyl phthalate, dibutyl phthalate, and diisobutyl phthalate;

[0028] Preferably, the amount of the solvent is 60 to 200 times, such as 80 times, 100 times, 120 times, 150 times, 180 times, etc., of the feed amount of the β-lactone intermediate per minute.

[0029] In the present invention, the reverse cycloaddition reaction in step 2) uses an organic phosphoric acid as a catalyst, which may be but is not limited to any one of phenylphosphoric acid, diphenylphosphoric acid, diphenyl phosphate, di(4-methylphenyl) phosphate, bis(2,4-di-tert-butylphenyl) phosphate, bis(p-nitrophenyl) phosphate, etc.;

[0030] Preferably, the amount of the organic phosphoric acid catalyst is 0.02-0.5% of the molar amount of the β-lactone intermediate, such as 0.1%, 0.15%, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, etc., and the organic phosphoric acid catalyst is added to the bottom solvent at one time.

[0031] In the present invention, the reaction distillation conditions are as follows: the number of plates is 10-20, such as 12, 15, 18, etc., the tower top temperature is 90-95°C, such as 91°C, 92°C, 93°C, 94°C, etc., the tower bottom temperature is 105-120°C, such as 110°C, 115°C, etc., the reflux ratio is 5:1-1:1, such as 4:1, 3:1, 2:1, etc., and the tower top pressure is 0.5-2.0 kPaA, such as 1.0 kPaA, 1.5 kPaA, etc.; the β-lactone intermediate tower bottom is continuously fed, and high myrcene and CO are taken out from the tower top. 2 , where high myrcene is condensed and liquefied and collected in a receiving bottle, CO 2 Expelled in the form of gas.

[0032] The present invention adopts the above technical solution and has the following positive effects:

[0033] 1. The method of the present invention has a short and novel synthetic route. It uses easily available 8-methyl-2,7-nonadien-4-one as a raw material, and obtains a homomyrcene product simply and efficiently through a two-step reaction of [2+2] cycloaddition and reverse cycloaddition. The overall yield of the route is high. Compared with the traditional process using citral addition-dehydration method, the yield and product content are significantly improved, which is conducive to the development of downstream derivatives of homomyrcene such as Georges-Rosmarinus.

[0034] 2. The reverse cycloaddition reaction in the method of the present invention adopts a reactive distillation process, and the bottom of the tower uses a high-boiling point phthalate as a buffer solvent. After the raw materials are cracked into products in the bottom of the tower, they can be quickly evaporated and vaporized, avoiding side reactions such as isomerization and polymerization of the polyene structure product under the action of the bottom catalyst.

[0035] 3. The present invention uses a trace amount of organic phosphoric acid as a catalyst for the reverse cycloaddition reaction, realizes an efficient ring-opening reaction of the β-lactone intermediate, obtains the target product, high myrcene, with high conversion rate and selectivity, and has high catalyst activity, long life and low cost. DETAILED DESCRIPTION

[0036] The present invention is described in detail below by examples, but the present invention is not limited to the following examples.

[0037] The main raw material information is as follows:

[0038] Boron trifluoride etherate, Sigma-Aldrich reagent, 99%. Ethyl acetate, Aladdin reagent, chromatographic grade; Sodium bicarbonate, Sinopharm reagent, AR. Boron trifluoride acetic acid, Alfa reagent, 99%. Zinc bromide, aluminum chloride, Aladdin reagent, 99%. Anhydrous tetrahydrofuran, dichloroethane, butyl acetate, Aladdin reagent, chromatographic grade. Potassium bicarbonate, sodium carbonate, West Asia reagent, 99%. Diammonium hydrogen phosphate, Myrel reagent, AR.

[0039] Dibutyl phthalate, diethyl phthalate, diisopropyl phthalate, dimethyl phthalate, Aladdin reagent, AR. Diphenylphosphoric acid, diphenyl phosphate, Hongjiang reagent, 99%. Di(4-methylphenyl) phosphate, Bailingwei reagent, 98%. Bis(2,4-di-tert-butylphenyl) phosphate, Bid Pharmaceutical, 97%. 8-Methyl-2,7-nonadien-4-one, Atuo reagent, 98%.

[0040] The gas chromatography test conditions of the present invention are as follows:

[0041] Instrument model: Agilent 7890B; Chromatographic column: Capillary column HB-5 (30m×0.30mm×0.25μm); Initial temperature 80℃, increased to 150℃ at a rate of 10℃ / min; then increased to 220℃ at a rate of 20℃ / min, maintained for 5.0min; finally increased to 240℃ at a rate of 10℃ / min, maintained for 3.0min. Carrier gas high-purity nitrogen, split ratio 40:1, split flow 40mL / min. Carrier gas saving: 38mL / min, start waiting time 5.0min. Injection temperature 220℃, 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] Synthesis of β-lactone intermediates from 8-methyl-2,7-nonadien-4-one and ketene catalyzed by boron trifluoride etherate

[0044] Weigh boron trifluoride etherate (1.41 g, 9.9 mmol), anhydrous ethyl acetate (150.71 g), and 8-methyl-2,7-nonadien-4-one (50.24 g, 0.33 mol), and add them in turn to a 1000 mL three-necked flask that has been replaced with nitrogen in advance, place the three-necked flask in a low-temperature cold bath, start stirring, reduce the temperature of the reaction liquid in the flask to 0°C and maintain it, and then slowly introduce ketene gas into the reaction flask. The ketene gas is obtained by high-temperature cracking of diketene, and its feed rate is maintained at 45.2 mL / min (0.12 mol / h); the ketene gas feed conduit is inserted below the liquid surface so that the ketene can quickly dissolve into the reaction liquid and participate in the reaction; in order to prevent the reaction flask from being pressurized, the tail gas is discharged from the conduit, and is discharged into the fume hood after being absorbed by sodium hydroxide aqueous solution. After continuous feeding for 3 hours, the ketene feeding was stopped; the reaction solution was sampled and the composition was detected by GC. The raw material 8-methyl-2,7-nonadien-4-one was basically reacted, and the selectivity of the [2+2] cycloaddition product propiolactone intermediate was 98%. Then, sodium bicarbonate aqueous solution (18.3 g, 5.0 wt%, 10.9 mmol) was added to quench the reaction, and the reaction solution was allowed to stand for phase separation, and the aqueous phase was extracted with ethyl acetate (30 mL); the organic phases were combined, then washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, and then the solvent and the product were separated by reduced pressure distillation, and the yield of the target product was 95%. High-resolution mass spectrum of the product HRMS-EI M + calcd C 12 H 18 O 2 :194.1307, found 194.1306. 1 HNMR(400MHz)δ1.57(t,2H),1.67(d,3H),1.79(d,3H),1.96(m,2H),2.05(d,3H),3.40(dd,2H),5.20(m,1H),5.67-5.69(m,2H).

[0045] Example 2

[0046] Synthesis of β-lactone intermediates from 8-methyl-2,7-nonadien-4-one and ketene catalyzed by boron trifluoride etherate

[0047] Weigh boron trifluoride etherate (0.11 g, 0.8 mmol), anhydrous ethyl acetate (182.68 g), and 8-methyl-2,7-nonadien-4-one (60.89 g, 0.40 mol), and add them in turn to a 1000 mL three-necked flask that has been replaced with nitrogen in advance, place the three-necked flask in a low-temperature cold bath, start stirring, reduce the temperature of the reaction liquid in the flask to 20°C and maintain it, then slowly introduce ketene gas into the reaction flask. Ketene gas is obtained by high-temperature cracking of diketene, and its feed rate is maintained at 37.3 mL / min (0.10 mol / h); the ketene gas feed conduit is inserted below the liquid surface so that ketene can quickly dissolve into the reaction liquid and participate in the reaction; in order to prevent the reaction flask from being pressurized, the tail gas is discharged from the conduit, and is discharged into the fume hood after being absorbed by sodium hydroxide aqueous solution. After 6 hours of continuous feeding, the ketene feeding was stopped; the reaction solution was sampled and the composition was detected by GC. The raw material 8-methyl-2,7-nonadien-4-one was basically reacted completely, and the selectivity of the [2+2] cycloaddition product propiolactone intermediate was 97%. Then, sodium bicarbonate aqueous solution (8.1 g, 1.0 wt%, 1.0 mmol) was added to quench the reaction, and the reaction solution was allowed to stand for phase separation, and the aqueous phase was extracted with ethyl acetate (30 mL); the organic phases were combined, then washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, and then the solvent and the product were separated by reduced pressure distillation, and the yield of the target product was 94%.

[0048] Example 3

[0049] Synthesis of β-lactone intermediates from 8-methyl-2,7-nonadien-4-one and ketene catalyzed by boron trifluoride etherate

[0050] Weigh boron trifluoride etherate (0.41 g, 2.9 mmol), anhydrous ethyl acetate (220.74 g), and 8-methyl-2,7-nonadien-4-one (44.15 g, 0.29 mol), and add them in turn to a 1000 mL three-necked flask that has been replaced with nitrogen in advance, place the three-necked flask in a low-temperature cold bath, start stirring, raise the temperature of the reaction liquid in the flask to 30°C and keep it stable, then slowly introduce ketene gas into the reaction flask. Ketene gas is obtained by high-temperature cracking of diketene, and its feed rate is maintained at 46.9 mL / min (0.126 mol / h); the ketene gas feed conduit is inserted below the liquid surface so that ketene can quickly dissolve in the reaction liquid and participate in the reaction; in order to prevent the reaction flask from being pressurized, the tail gas is discharged from the conduit, and is discharged into the fume hood after being absorbed by sodium hydroxide aqueous solution. After continuous feeding for 3 hours, the ketene feeding was stopped, and the reaction was continued at 30°C for 10 minutes; the reaction solution was sampled, and the composition was detected by GC. The raw material 8-methyl-2,7-nonadien-4-one was basically reacted, and the selectivity of the [2+2] cycloaddition product propiolactone intermediate was 98%. Then, sodium bicarbonate aqueous solution (13.4g, 2.0wt%, 3.2mmol) was added to quench the reaction, and the reaction solution was allowed to stand for phase separation, and the aqueous phase was extracted with ethyl acetate (30mL); the organic phases were combined, then washed with saturated brine (30mL), dried over anhydrous sodium sulfate, and then the solvent and the product were separated by reduced pressure distillation, and the yield of the target product was 97%.

[0051] Example 4

[0052] Synthesis of β-lactone intermediates from 8-methyl-2,7-nonadien-4-one and ketene catalyzed by boron trifluoride and acetic acid

[0053] Weigh trifluoroboric acid (0.52 g, 4.1 mmol), dichloroethane (164.4 g), and 8-methyl-2,7-nonadien-4-one (41.1 g, 0.27 mol), and add them in turn to a 1000 mL three-necked flask that has been replaced with nitrogen in advance, place the three-necked flask in a low-temperature cold bath, start stirring, lower the temperature of the reaction liquid in the flask to 20°C and keep it stable, then slowly introduce ketene gas into the reaction flask. The ketene gas is obtained by high-temperature cracking of diketene, and its feed rate is maintained at 30.2 mL / min (0.081 mol / h); the ketene gas feed conduit is inserted below the liquid surface so that the ketene can quickly dissolve in the reaction liquid and participate in the reaction; in order to prevent the reaction flask from being pressurized, the tail gas is discharged from the conduit, and is discharged into the fume hood after being absorbed by sodium hydroxide aqueous solution. After continuous feeding for 4 hours, the ketene feeding was stopped and the reaction was continued at 20°C for 0.5h; the reaction solution was sampled and the composition was detected by GC. The raw material 8-methyl-2,7-nonadien-4-one was basically reacted completely, and the selectivity of the [2+2] cycloaddition product propiolactone intermediate was 98%. Then potassium bicarbonate aqueous solution (22.3g, 2.0wt%, 4.5mmol) was added to quench the reaction, the reaction solution was allowed to stand and then phase separated, and the aqueous phase was extracted with dichloroethane (30mL); the organic phases were combined, then washed with saturated brine (30mL), dried over anhydrous sodium sulfate, and then the solvent and the product were separated by reduced pressure distillation, and the yield of the target product was 96%.

[0054] Example 5

[0055] Synthesis of β-lactone intermediates from 8-methyl-2,7-nonadien-4-one and ketene catalyzed by zinc bromide

[0056] Weigh zinc bromide (1.31 g, 5.8 mmol), anhydrous butyl acetate (220.74 g), and 8-methyl-2,7-nonadien-4-one (44.15 g, 0.29 mol), and add them in turn to a 1000 mL three-necked flask that has been replaced with nitrogen in advance, place the three-necked flask in a low-temperature cold bath, start stirring, raise the temperature of the reaction liquid in the flask to 40°C and keep it constant, then slowly introduce ketene gas into the reaction flask. Ketene gas is obtained by high-temperature cracking of diketene, and its feed rate is maintained at 26.0 mL / min (0.07 mol / h); the ketene gas feed conduit is inserted below the liquid surface so that ketene can quickly dissolve into the reaction liquid and participate in the reaction; in order to prevent the reaction flask from being pressurized, the tail gas is discharged from the conduit, and is discharged into the fume hood after being absorbed by sodium hydroxide aqueous solution. After continuous feeding for 5 hours, the ketene feeding was stopped, and the reaction was continued at 40°C for 10 minutes; the reaction solution was sampled, and the composition was detected by GC. The raw material 8-methyl-2,7-nonadien-4-one was basically reacted, and the selectivity of the [2+2] cycloaddition product propiolactone intermediate was 96%. Then, sodium carbonate aqueous solution (20.5g, 3.0wt%, 5.8mmol) was added to quench the reaction, and the reaction solution was allowed to stand for phase separation, and the aqueous phase was extracted with butyl acetate (30mL); the organic phases were combined, then washed with saturated brine (30mL), dried over anhydrous sodium sulfate, and then the solvent and the product were separated by reduced pressure distillation, and the yield of the target product was 93%.

[0057] Example 6

[0058] Synthesis of β-lactone intermediates from 8-methyl-2,7-nonadien-4-one and ketene catalyzed by aluminum chloride

[0059] Weigh aluminum chloride (0.70 g, 5.0 mmol), anhydrous tetrahydrofuran (226.07 g), and 8-methyl-2,7-nonadien-4-one (50.24 g, 0.33 mol), and add them in turn to a 1000 mL three-necked flask that has been replaced with nitrogen in advance, place the three-necked flask in a low-temperature cold bath, start stirring, lower the temperature of the reaction liquid in the flask to 20°C and maintain it, then slowly introduce ketene gas into the reaction flask. Ketene gas is obtained by high-temperature cracking of diketene, and its feed rate is maintained at 22.6 mL / min (0.061 mol / h); the ketene gas feed conduit is inserted below the liquid surface so that ketene can quickly dissolve into the reaction liquid and participate in the reaction; in order to prevent the reaction flask from being pressurized, the tail gas is discharged from the conduit, and is discharged into the fume hood after being absorbed by sodium hydroxide aqueous solution. After 6 hours of continuous feeding, the ketene feeding was stopped; the reaction solution was sampled and the composition was detected by GC. The raw material 8-methyl-2,7-nonadien-4-one was basically reacted completely, and the selectivity of the [2+2] cycloaddition product propiolactone intermediate was 98%. Then, diammonium hydrogen phosphate aqueous solution (15.7 g, 5.0 wt%, 5.9 mmol) was added to quench the reaction, and the reaction solution was allowed to stand for phase separation, and the aqueous phase was extracted with ethyl acetate (30 mL); the organic phases were combined, then washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, and then the solvent and the product were separated by reduced pressure distillation, and the yield of the target product was 96%.

[0060] Embodiment 7:

[0061] Obtaining Homomyrcene by Reactive Distillation and Cracking of β-lactone Intermediates

[0062] In a nitrogen atmosphere, solvent dibutyl phthalate (73.8 g) and catalyst diphenylphosphoric acid (0.415 g, 1.9 mmol) were added to a 250 mL three-necked flask equipped with a magnetic stirrer at room temperature, and a clear transparent liquid was obtained after stirring. A 0.5 m long distillation column and a reflux ratio controller were connected directly above the three-necked flask, and a 3*3 triangular spiral packing was filled in the distillation column, and the total number of plates was 15. The three-necked flask was placed in a 115°C oil bath, stirring and condensing water were turned on, the top vacuum system was started, and the top pressure was controlled at 0.5 kPa. After the temperature of the tower reactor was raised to 105°C, a β-lactone intermediate (1.23 g / min) was slowly fed to the tower reactor three-necked flask using a horizontal flow pump, and there was no extraction from the tower reactor. The cracking product was extracted from the top of the tower, and the target product was obtained after condensation and gas-liquid phase separation. The tower top was sampled and analyzed, a certain amount of n-decane was added as an internal standard, and then analyzed by GC chromatography. The conversion rate of β-lactone intermediate was >99%, and the selectivity of the target isomer of homomyrcene was 96%. The high-resolution mass spectrum data of the product homomyrcene are as follows: HRMS-EI M + calcd C 11 H 18 :150.1409,found 150.1407.1 H NMR (400MHz) δ1.58(d,3H),1.65(s,3H),1.72(s,3H),2.25(m,4H),5.02(m,2H),5.18(m,1H),5.22(m,1H),6.41(m,1H).

[0063] Embodiment 8:

[0064] Obtaining Homomyrcene by Reactive Distillation and Cracking of β-lactone Intermediates

[0065] In a nitrogen atmosphere, solvent dibutyl phthalate (95.8 g) and catalyst diphenylphosphoric acid (0.081 g, 0.4 mmol) were added to a 250 mL three-necked flask equipped with a magnetic stirrer at room temperature, and a clear transparent liquid was obtained after stirring. A 0.5 m long distillation column and a reflux ratio controller were connected directly above the three-necked flask, and a 3*3 triangular spiral packing was filled in the distillation column, and the total number of plates was 15. The three-necked flask was placed in a 120°C oil bath, stirring and condensing water were turned on, and the top vacuum system was started, and the top pressure was controlled at about 0.8 kPa. After the temperature of the tower reactor was raised to 110°C, a β-lactone intermediate (0.8 g / min) was slowly fed to the tower reactor three-necked flask using a horizontal flow pump, and there was no extraction from the tower reactor. The cracking product was extracted from the top of the tower, and the target product was obtained after condensation and gas-liquid phase separation. Sampling was performed on the top of the tower, and a certain amount of n-decane was added as an internal standard. Then, GC chromatography was used for analysis. The conversion rate of the β-lactone intermediate was >99%, and the selectivity of the target isomer of homomyrcene was 92%.

[0066] Embodiment 9:

[0067] Obtaining Homomyrcene by Reactive Distillation and Cracking of β-lactone Intermediates

[0068] In a nitrogen atmosphere, solvent dibutyl phthalate (113.3 g) and catalyst diphenylphosphoric acid (0.153 g, 0.7 mmol) were added to a 250 mL three-necked flask equipped with a magnetic stirrer at room temperature, and a clear transparent liquid was obtained after stirring. A 0.5 m long distillation column and a reflux ratio controller were connected directly above the three-necked flask, and a 3*3 triangular spiral packing was filled in the distillation column, and the total number of plates was 15. The three-necked flask was placed in a 130°C oil bath, stirring and condensing water were turned on, and the top vacuum system was started, and the top pressure was controlled at 2.0 kPa. After the temperature of the tower reactor was raised to 120°C, a β-lactone intermediate (0.57 g / min) was slowly fed to the tower reactor three-necked flask using a horizontal flow pump, and there was no extraction from the tower reactor. The cracking product was extracted from the top of the tower, and the target product was obtained after condensation and gas-liquid phase separation. Sampling was performed on the top of the tower, and a certain amount of n-decane was added as an internal standard. Then, GC chromatography was used for analysis. The conversion rate of the β-lactone intermediate was >99%, and the selectivity of the target isomer of homomyrcene was 93%.

[0069] Embodiment 10:

[0070] Obtaining Homomyrcene by Reactive Distillation and Cracking of β-lactone Intermediates

[0071] In a nitrogen atmosphere, solvent diethyl phthalate (77.7 g) and catalyst diphenyl phosphate (0.080 g, 0.3 mmol) were added to a 250 mL three-necked flask equipped with a magnetic stirrer at room temperature, and a clear transparent liquid was obtained after stirring. A 0.5 m long distillation column and a reflux ratio controller were connected directly above the three-necked flask, and a 3*3 triangular spiral packing was filled in the distillation column, and the total number of plates was 15. The three-necked flask was placed in a 125°C oil bath, stirring and condensing water were turned on, and the top vacuum system was started, and the top pressure was controlled at about 1.0 kPa. After the temperature of the tower reactor was raised to 115°C, a β-lactone intermediate (0.52 g / min) was slowly fed to the tower reactor three-necked flask using a horizontal flow pump, and there was no extraction from the tower reactor. The cracking product was extracted from the top of the tower, and the target product was obtained after condensation and gas-liquid phase separation. Sampling was performed on the top of the tower, and a certain amount of n-decane was added as an internal standard. Then, GC chromatography was used for analysis. The conversion rate of the β-lactone intermediate was >99%, and the selectivity of the target isomer of homomyrcene was 92%.

[0072] Embodiment 11:

[0073] Obtaining Homomyrcene by Reactive Distillation and Cracking of β-lactone Intermediates

[0074] In a nitrogen atmosphere, solvent diisopropyl phthalate (93.3 g) and catalyst di(4-methylphenyl) phosphate (0.050 g, 0.2 mmol) were added to a 250 mL three-necked flask equipped with a magnetic stirrer at room temperature, and a clear transparent liquid was obtained after stirring. A 0.5 m long distillation column and a reflux ratio controller were connected directly above the three-necked flask, and a 3*3 triangular spiral packing was filled in the distillation column, and the total number of plates was 15. The three-necked flask was placed in a 125°C oil bath, stirring and condensing water were turned on, and the top vacuum system was started, and the top pressure was controlled at about 1.0 kPa. After the temperature of the tower bottom was raised to 115°C, a β-lactone intermediate (0.58 g / min) was slowly fed to the tower bottom three-necked flask using a horizontal flow pump, and there was no extraction from the tower bottom. The cracking product was extracted from the top of the tower, and the target product was obtained after condensation and gas-liquid phase separation. Sampling was performed on the top of the tower, and a certain amount of n-decane was added as an internal standard. Then, GC chromatography was used for analysis. The conversion rate of the β-lactone intermediate was >99%, and the selectivity of the target isomer of homomyrcene was 94%.

[0075] Embodiment 12:

[0076] Obtaining Homomyrcene by Reactive Distillation and Cracking of β-lactone Intermediates

[0077] In a nitrogen atmosphere, solvent dimethyl phthalate (113.65 g) and catalyst bis(2,4-di-tert-butylphenyl) phosphate (0.037 g, 0.1 mmol) were added to a 250 mL three-necked flask equipped with a magnetic stirrer at room temperature, and a clear transparent liquid was obtained after stirring. A 0.3 m long distillation column and a reflux ratio controller were connected directly above the three-necked flask, and a 3*3 triangular spiral packing was filled in the distillation column, and the total number of plates was 10. The three-necked flask was placed in a 120°C oil bath, stirring and condensing water were turned on, and the top vacuum system was started, and the top pressure was controlled at 0.8 kPa. After the temperature of the tower bottom was raised to 110°C, a β-lactone intermediate (0.76 g / min) was slowly fed into the tower bottom three-necked flask using a horizontal flow pump, and there was no extraction from the tower bottom. The cracking product was extracted from the top of the tower, and the target product was obtained after condensation and gas-liquid phase separation. Sampling was performed on the top of the tower, and a certain amount of n-decane was added as an internal standard. Then, GC chromatography was used for analysis. The conversion rate of the β-lactone intermediate was >99%, and the selectivity of the target isomer of homomyrcene was 95%.

Claims

1. A method for synthesizing high-purity homomyrcene, characterized in that: The steps include: 1) 8-methyl-2,7-nonadien-4-one and vinyl ketone undergo a [2+2] cycloaddition reaction in the presence of a catalyst to obtain a β-lactone intermediate; 2) The β-propiolactone intermediate undergoes a reverse cycloaddition reaction to release a molecule of CO2 to obtain high-purity homomyrcene.

2. The synthesis method according to claim 1, characterized in that The catalyst in step 1) is a Lewis acid catalyst, preferably one or more of boron trifluoride etherate, boron trifluoride acetic acid, zinc chloride, zinc bromide, zinc acetate, zinc acetylacetonate, ferric chloride, aluminum chloride, scandium trifluoromethanesulfonate, and yttrium trifluoromethanesulfonate; Preferably, the amount of the catalyst is 0.2 to 3.0% of the molar amount of 8-methyl-2,7-nonadien-4-one; More preferably, the molar ratio of 8-methyl-2,7-nonadien-4-one to ketene is 1.0:1.1-1.

5.

3. The synthesis method according to claim 1 or 2, characterized in that The [2+2] cycloaddition reaction in step 1) is carried out under solvent conditions; Preferably, the solvent is selected from one or more polar or non-polar aprotic solvents, preferably one or more of toluene, ether, methyl tert-butyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, methyl acetate, ethyl acetate, butyl acetate, ethyl butyrate, dichloromethane, chloroform, and dichloroethane; More preferably, the amount of the solvent used is 3.0 to 5.0 times the mass of 8-methyl-2,7-nonadien-4-one.

4. The synthesis method according to any one of claims 1 to 3, characterized in that Step 1) the [2+2] cycloaddition reaction, the reaction temperature is 0 to 40°C; the reaction time is 3 to 6 hours; Preferably, the [2+2] cycloaddition reaction adopts a semi-continuous process, 8-methyl-2,7-nonadien-4-one, solvent and catalyst are added at one time, and ketene is continuously added to the above mixed solution.

5. The synthesis method according to any one of claims 1 to 4, characterized in that After the [2+2] cycloaddition reaction in step 1) is completed, a step of adding a terminator to quench the reaction is also included; Preferably, the terminator is an inorganic weak base, preferably one or more of sodium bicarbonate, potassium bicarbonate, sodium carbonate, potassium carbonate, potassium monohydrogen phosphate, ammonium phosphate, diammonium hydrogen phosphate, and lithium carbonate; Preferably, the amount of the terminator is 100-120% of the molar amount of the catalyst.

6. The synthesis method according to claim 1, characterized in that Step 2) The reverse cycloaddition reaction is carried out in a reactive distillation tower, and the β-lactone intermediate is continuously fed into the bottom of the tower and undergoes a reverse cycloaddition reaction to generate the product homomyrcene and CO2, and the product is vaporized and evaporated and taken out from the top of the tower.

7. The synthesis method according to claim 6, characterized in that Adding solvent into the reactor of the reactive distillation tower; Preferably, the solvent is selected from any one of dimethyl phthalate, diethyl phthalate, dipropyl phthalate, diisopropyl phthalate, dibutyl phthalate and diisobutyl phthalate; More preferably, the amount of the solvent is 60 to 200 times the mass of the β-lactone intermediate fed in one minute.

8. The synthesis method according to claim 1, 6 or 7, characterized in that: Step 2) The reverse cycloaddition reaction uses an organic phosphoric acid as a catalyst, preferably selected from any one of phenyl phosphoric acid, diphenyl phosphoric acid, diphenyl phosphate, di(4-methylphenyl) phosphate, bis(2,4-di-tert-butylphenyl) phosphate, and bis(p-nitrophenyl) phosphate; Preferably, the amount of the organic phosphoric acid catalyst is 0.02-0.5% of the molar amount of the β-lactone intermediate; More preferably, the organic phosphoric acid catalyst is added into the bottom solvent at one time.

9. The synthesis method according to any one of claims 6 to 8, characterized in that: The reaction distillation conditions are as follows: the number of plates is 10-20, the tower top temperature is 90-95° C., the tower bottom temperature is 105-120° C., the reflux ratio is 5:1 to 1:1, and the tower top pressure is 0.5-2.0 kPaA.

10. The synthesis method according to claim 9, characterized in that During the reactive distillation process, the β-lactone intermediate is continuously fed into the bottom of the tower, and homomyrcene and CO2 are extracted from the top of the tower, wherein homomyrcene is condensed and liquefied and then collected in a receiving bottle, and CO2 is discharged in the form of gas.

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