CN113979847B - Method for synthesizing 6-methyl-5-octen-2-one by carbonyl-ene reaction - Google Patents
Method for synthesizing 6-methyl-5-octen-2-one by carbonyl-ene reaction Download PDFInfo
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Abstract
Disclosed herein is a method of synthesizing 6-methyl-5-octen-2-one, the method comprising: the 3-methyl pent-2-enal and 2-methoxy propylene are subjected to carbonyl-ene reaction under the action of a catalyst to obtain a 3-hydroxy olefine ether intermediate, and the intermediate is subjected to dehydration and hydrogenation reaction to obtain 6-methyl-5-octen-2-one. The synthesis route is short, the phosphate and alkyl zinc are used for concerted catalysis, a small amount of catalyst can complete the catalysis, and the yield of the obtained 3-hydroxy vinyl ether is high. The chemical conversion from 3-hydroxyolefine ether to 6-methyl-5-octen-2-one is completed by one-pot method through acid and hydrogenation catalysis, the operation is simplified, only methanol is byproduct, and three wastes are not generated.
Description
Technical Field
The application generally belongs to the field of fine chemical engineering, and particularly relates to a method for synthesizing 6-methyl-5-octene-2-one by using 3-methyl-2-pentenal and 2-alkoxy propylene as raw materials through carbonyl-alkene reaction and hydrogenation reaction, wherein the product is one of key intermediates for synthesizing rare spice ethyl linalool.
Background
Ethyl linalool, chemical name 3,7-dimethyl-1,6-nonadien-3-ol, is a colorless or pale yellow liquid at normal temperature, has very fresh floral aroma, has similar floral aroma to linalool, but is more durable and soft than linalool, is favored by perfumers, and is increased year by year at present in daily chemical product utilization rate and consumption, and is more and more favored by people. The ethyl linalool can be used for preparing rose, lily of the valley, tuberose, lilac, vanilla, acacia, orange flower and other fragrance types, the application of the ethyl linalool is not limited by the type of the fragrance, and the ethyl linalool is particularly suitable for perfumed soap or wax essence. Because the ethyl linalool has a higher boiling point than the linalool, the fragrance retention effect of the ethyl linalool is better than that of the linalool, and the future application can be further expanded. In the production process of the ethyl linalool, the 6-methyl-5-octen-2-one is a key intermediate, and according to the results of current literature reports and patent researches, the synthetic method of the intermediate is quite few, so that the high-efficiency synthesis of the ethyl linalool is limited.
In the literature and patent reports known at present, the most used method for synthesizing 6-methyl-5-octen-2-one is rearrangement reaction of 3-methyl-1-penten-3-ol, for example, saucy-Marbet rearrangement of 3-methyl-1-penten-3-ol and 2-methoxypropene, and one molecule of methanol is removed to obtain 6-methyl-5-octen-2-one.
Patents WO2018091623, EP3323802 use phosphate as catalyst and yield 93% was obtained. The used phosphate ester catalyst has complex structure, high price and high cost in practical application, and the method has long reaction time (more than 10 hours) and time-consuming operation.
Also 3-methyl-1-pentene-3-ol and 2-methoxy are used as raw materials, patent WO2017097884 uses triethanolamine phosphate as a catalyst, but only a 25% reaction yield is obtained.
In addition to the synthesis of 6-methyl-5-octen-2-one by Saucy-Marbet reaction, some reports adopt Carroll rearrangement reaction to synthesize 6-methyl-5-octen-2-one, for example, pogrebnoi et al report the use of organic aluminum salt as catalyst, acetoacetate as rearrangement reagent, and 3-methyl-1-penten-3-ol to carry out rearrangement reaction, remove one molecule of methanol and carbon dioxide, finally obtain 6-methyl-5-octen-2-one, the reaction yield is moderate, and reaches 78% (Tetrahedron Letters,1987,28,4893-6).
In summary, the most important synthesis method of 6-methyl-5-octen-2-one is to obtain 3-methyl-1-penten-3-ol by Saucy-Marbet rearrangement or Carroll rearrangement reaction. However, the Saucy-Marbet rearrangement requires the use of phosphate ester with a complex structure and a high price as a catalyst to obtain a good yield; the yield of the Carroll rearrangement is moderate, equivalent methanol and carbon dioxide byproducts are generated, and the atom economy is general. The related documents and patents report less, and most of the documents report lower yield.
At present, a novel synthesis route of 6-methyl-5-octen-2-one needs to be developed, and 6-methyl-5-octen-2-one is synthesized efficiently, environmentally and environmentally from low-price raw materials.
Disclosure of Invention
The application aims at providing a high-efficiency synthesis method of 6-methyl-5-octen-2-one, which takes 3-methylpent-2-enal and 2-methoxypropene as raw materials to obtain a 3-hydroxy alkene ether intermediate through carbonyl-alkene reaction; the intermediate is then dehydrated, hydrogenated and the like under the action of acid and a hydrogenation catalyst to obtain the 6-methyl-5-octen-2-one. The method has the advantages of simple route, mild conditions and environmental friendliness.
One or more embodiments provide a method for synthesizing 6-methyl-5-octen-2-one by carbonyl-ene reaction, the method comprising the following reaction:
s1: reacting 3-methyl-2-pentenal with 2-alkoxy propylene carbonyl-ene to obtain a 3-hydroxy alkene ether intermediate;
s2: under the action of acid and hydrogenation catalyst, the 3-hydroxy vinyl ether is dehydrated and hydrogenated to obtain 6-methyl-5-octene-2-one.
In one or more embodiments, the 2-alkoxypropene is 2-methoxypropene, 2-ethoxypropene, 2-propoxypropene, or 2-butoxypropene.
The reaction scheme is schematically as follows:
wherein R is alkyl; such as methyl, ethyl, propyl or butyl.
In one or more embodiments, the 2-alkoxypropylene includes, but is not limited to, 2-methoxypropene, 2-ethoxypropene, 2-propoxypropene, 2-butoxypropene.
In one or more embodiments, the 2-alkoxypropene is 2-methoxypropene or 2-ethoxypropene;
in one or more embodiments, the molar amount of 2-alkoxypropene ranges from 100% to 200%, such as 100%, 110%, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190%, or 200% of the molar amount of 3-methyl-2-pentenal.
In one or more embodiments, the S1 reaction catalyst is prepared in situ from an organozinc and a phosphate ester.
In one or more embodiments, the organozinc includes, but is not limited to, one or more of dimethylzinc, diethylzinc, dipropylzinc, diisopropylzinc.
In one or more embodiments, the organozinc is dimethyl zinc or diethyl zinc.
In one or more embodiments, the molar amount of the organozinc is 0.01% to 1.0% of the molar amount of 3-methyl-2-pentenal, e.g., 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, or 1.0%.
In one or more embodiments, the phosphate ester includes, but is not limited to, one or more of dimethyl phosphate, diethyl phosphate, diphenyl phosphate, ditolyl phosphate, dibenzyl phosphate, diisooctyl phosphate.
In one or more embodiments, the phosphate ester is diphenyl phosphate or ditolyl phosphate.
In one or more embodiments, the molar amount of phosphate ester is 0.01% to 1.0% of the molar amount of 3-methyl-2-pentenal, e.g., 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, or 1.0%.
In one or more embodiments, an aprotic solvent is used in S1.
In one or more embodiments, the solvent used in S1 includes, but is not limited to, n-hexane, n-heptane, toluene, xylene, diethyl ether, tetrahydrofuran, methyl-t-butyl ether, dichloromethane, dichloroethane.
In one or more embodiments, the solvent used in S1 is dichloromethane or toluene.
In one or more embodiments, the reaction of S1 is a batch reaction, a semi-batch reaction, or a continuous reaction.
In one or more embodiments, the reaction time of S1 is 1 to 4 hours; and/or the reaction temperature is-20 to 30 ℃; and/or the reaction pressure is atmospheric (1 bar).
In one or more embodiments, after the S1 reaction is complete, distillation is directly performed to recover excess 2-alkoxypropene, which is then subjected to a de-heavy separation to provide a 3-hydroxyenol ether intermediate.
In one or more embodiments, a one-pot process using an acid and a hydrogenation catalyst in the S2 yields 6-methyl-5-octen-2-one.
In one or more embodiments, the acid includes, but is not limited to, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, hydrochloric acid, or sulfuric acid.
In one or more embodiments, the acid is methanesulfonic acid or p-toluenesulfonic acid.
In one or more embodiments, the molar amount of the acid is 0.1 to 2.0% of the molar amount of the 3-hydroxyvinylether, e.g., 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, or 2.0%.
In one or more embodiments, the hydrogenation catalyst is 0.5 to 10.0% palladium on carbon, 0.5 to 10.0% palladium on alumina, 0.5 to 10.0% palladium on calcium carbonate, 0.5 to 10.0% palladium on barium sulfate, or 0.5 to 10.0% palladium on calcium sulfate. The term "0.5 to 10.0% of palladium" means the amount of palladium supported, for example, 0.5 to 10.0% of palladium on carbon means 0.5 to 10.0% by weight of palladium supported on carbon, that is, 0.5 to 10.0% by weight of palladium supported on carbon, and the same applies to the other cases.
In one or more embodiments, the hydrogenation catalyst is 0.5 to 10.0% palladium barium sulfate or 0.5 to 10.0% palladium calcium sulfate.
In one or more embodiments, the hydrogenation catalyst has a mass that is between 0.5% and 2.0% of the mass of the 3-hydroxyvinylether, e.g., 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, or 2.0%.
In one or more embodiments, wherein the reaction of S2 is carried out in an autoclave.
In one or more embodiments, the reaction solvent for S2 includes, but is not limited to, methanol, ethanol, propanol, isopropanol, n-butanol, 2-butanol, t-butanol, tetrahydrofuran, methyl t-butyl ether.
In one or more embodiments, the reaction solvent for S2 is ethanol, isopropanol, or tetrahydrofuran.
In one or more embodiments, the hydrogen pressure in the hydrogenation reaction is from 0.1 to 2.0MPa (e.g., 0.1MPa, 0.2MPa, 0.3MPa, 0.4MPa, 0.5MPa, 0.6MPa, 0.7MPa, 0.8MPa, 0.9MPa, 1.0MPa, 1.1MPa, 1.2MPa, 1.3MPa, 1.4MPa, 1.5MPa, 1.6MPa, 1.7MPa, 1.8MPa, 1.9MPa, or 2.0 MPa), the hydrogen is continuously fed, and the pressure remains stable during the reaction.
In one or more embodiments, the reaction temperature in S2 is 30-60 ℃ (e.g., 30, 40, 50, or 60 ℃) and the reaction time is 0.5-2h (0.5 h, 0.6h, 0.7h, 0.8h, 0.9h, 1.0h, 1.1h, 1.2h, 1.3h, 1.4h, 1.5h, 1.6h, 1.7h, 1.8h, 1.9h, or 2.0 h).
One or more embodiments of the present application provide compounds for preparing 6-methyl-5-octen-2-one having a structure represented by the following general formula:
wherein R is an alkyl group.
In one or more embodiments, R is C 1-10 Alkyl groups, for example alkyl groups having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms.
In one or more embodiments, R is methyl, ethyl, propyl, or butyl.
In one or more embodiments, the 6-methyl-5-octen-2-one is obtained by only two steps of reaction using 3-methylpent-2-enal and 2-alkoxypropene as starting materials, and the synthetic route is shortened.
In one or more embodiments, the use of phosphate esters in conjunction with zinc alkyls provides for high yields of 3-hydroxy vinyl ethers, which can be catalyzed with a small amount of catalyst.
In one or more embodiments, the chemical conversion of 3-hydroxyolefine ether to 6-methyl-5-octen-2-one is accomplished in a one-pot process using acid and hydrogenation catalysis, which simplifies the operation and produces only methanol as a byproduct and no other three wastes.
With one or more of the above embodiments, at least one of the following advantages is achieved:
1. the synthesis route is novel, and the raw materials of 3-methyl-2-pentenal and 2-methoxypropene are simple and easy to obtain, the reaction yield is high, and the method has good potential application value.
2. The preparation method adopts a phosphate-zinc catalyst which is prepared from organic zinc and phosphate in situ, the preparation process is simple to operate, the obtained catalyst has extremely high carbonyl-alkene catalytic reaction activity, a small amount of catalyst can complete catalysis, and the 3-hydroxy alkene ether can be obtained with high yield.
3. In the hydrogenation reaction, organic sulfonic acid and palladium barium sulfate are used for co-catalysis, and the chemical conversion from 3-hydroxy vinyl ether to 6-methyl-5-octene-2-ketone is completed by a one-pot method, so that the operation is simplified.
4. In the whole synthesis process, only one by-product of methanol is generated, wastewater is not generated basically, and the methanol by-product can be rectified, purified and recycled, so that the whole synthesis process is combined with green chemistry and atom economy atoms, and the advantages of the route are reflected.
Detailed Description
The present application will be described in detail below with reference to examples, but the present application is not limited to the following examples.
The main raw material information is as follows:
3-methyl-2-pentenal, 97% by Guangao Australia Biotech Co., ltd, hubei;
2-methoxy propylene, 2-ethoxy propylene and carbofuran reagent with the purity of 98-99 percent;
dimethyl zinc, diethyl zinc, diisopropyl zinc and an Aladdin reagent, the purity is 99 percent;
diphenyl phosphate, ditolyl phosphate, dimethyl phosphate, diethyl phosphate and avastin reagent in the purity of 97-98%;
dichloromethane, toluene, n-hexane, tetrahydrofuran, ethanol, isopropanol, alpha-aesar, chromatographically pure;
methanesulfonic acid, p-toluenesulfonic acid, carbofuran reagent, 98%;
palladium barium sulfate, palladium calcium sulfate and an avastin reagent.
The gas chromatography test conditions of the present invention are as follows:
the instrument model is as follows: agilent 7890B; a chromatographic column: capillary column HP-5 (60 m.times.0.30 mm. Times.0.25 μm); the initial temperature was 80 ℃ and the temperature was raised to 105 ℃ at a rate of 5 ℃/min; then the temperature is raised to 195 ℃ at the speed of 10 ℃/min and kept for 5min. Carrying high-purity nitrogen gas, the split ratio is 30. Carrier gas saving: 19mL/min, start wait time 3min. The sample injection temperature is 250 ℃, the detector is FID, the detector temperature is 250 ℃, the air flow is 350mL/min, the hydrogen flow is 30mL/min, the tail gas flow is 60mL/min, and the sample injection amount is 0.2 muL.
Example 1:
raw materials of 3-methyl-2-pentenal (300g, 3.06mol), 2-methoxypropene (325g, 4.51mol), a catalyst of dimethylzinc (1.45g, 0.015mol), diphenyl phosphate (3.75g, 0.015mol) and 300mL of dichloromethane were charged into a 2L reaction flask equipped with a mechanical stirrer, a thermocouple and a condenser, and the reaction temperature was controlled at 20 ℃ and stirred at normal pressure (1 bar) for 2 hours. After the reaction of S1 is finished, excess 2-methoxypropene is recovered by simple distillation, and then intermediate 3-hydroxyolefine ether 510.8g is obtained, and the calculated yield is 98.15%.
The 2L autoclave was cleaned, dried and sealed at room temperature, and 1MPa of nitrogen was charged to maintain the pressure for 30min, and the pressure in the autoclave did not decrease, demonstrating good sealing properties. The autoclave was vented, and the 3-hydroxyvinylether intermediate (300g, 1.76mol) obtained by the S1 reaction, methanesulfonic acid (1.7 g, 0.0177mol), hydrogenation catalyst 5% palladium barium sulfate (1.5 g), and solvent ethanol (200 mL) were added to the autoclave at a time. After all the materials are added, the autoclave is sealed again, nitrogen is charged and discharged for 3 times, each time under 0.5MPa, and the air in the autoclave is put inAnd (4) changing to nitrogen, and finally keeping the nitrogen pressure in the kettle at normal pressure. Firstly, starting the autoclave to stir at the rotation speed of 450rpm, then starting external heating, and introducing H after the temperature in the autoclave is raised to 45 DEG C 2 And (4) until the pressure in the kettle is 1MPa, then adjusting a hydrogen pressure reducing valve, maintaining the reaction pressure stable, and stirring for reaction for 1 hour. After the reaction is finished, stopping stirring, discharging hydrogen, sampling and carrying out GC analysis, and obtaining the conversion rate of the 3-hydroxy vinyl ether intermediate serving as the raw material>99 percent, and the selectivity of the target product 6-methyl-5-octen-2-one is 96.5 percent.
Example 2
Raw materials of 3-methyl-2-pentenal (300g, 3.06mol), 2-ethoxypropene (270g, 3.13mol), a catalyst of diethyl zinc (1.2g, 0.01mol), ditolyl phosphate (2.75g, 0.01mol) and a solvent of 350mL of toluene were charged into a 2L reaction flask equipped with a mechanical stirrer, a thermocouple and a condenser, and the reaction temperature was controlled at 0 ℃ and stirred at normal pressure (1 bar) for 1 hour. After the reaction of S1 is finished, excess 2-methoxypropene is recovered by simple distillation, and then intermediate 3-hydroxyolefine ether 550.9g is obtained, and the calculated yield is 97.8%.
The 2L autoclave was cleaned, dried and sealed at room temperature, 1.5MPa nitrogen was charged and the pressure was maintained for 30min, and the pressure in the autoclave did not decrease, demonstrating good sealing. The autoclave was vented and charged once with the 3-hydroxyenol ether intermediate (300g, 1.63mol) obtained by the S1 reaction, p-toluenesulfonic acid (1.2g, 0.0070 mol), 1% palladium calcium sulfate as a hydrogenation catalyst (6.0 g) and 300mL of tetrahydrofuran as a solvent. After all the materials are added, the autoclave is sealed again, nitrogen is charged and discharged for 3 times, each time under 0.5MPa, the air in the autoclave is replaced by nitrogen, and finally the pressure of the nitrogen in the autoclave is normal pressure. Firstly, starting the autoclave to stir at the rotation speed of 450rpm, then starting external heating, and introducing H after the temperature in the autoclave rises to 60 DEG C 2 And (4) until the pressure in the kettle is 1.5MPa, then adjusting a hydrogen pressure reducing valve, maintaining the reaction pressure stable, and stirring for reaction for 0.5h. After the reaction is finished, stopping stirring, discharging hydrogen, sampling and carrying out GC analysis, and obtaining the conversion rate of the 3-hydroxy vinyl ether intermediate serving as the raw material>99 percent, and the selectivity of the target product 6-methyl-5-octen-2-one is 96.7 percent.
Example 3
Raw materials of 3-methyl-2-pentenal (250g, 2.55mol), 2-methoxypropene (360g, 4.99mol), a catalyst of dimethyl zinc (2.5 g, 0.026mol), dimethyl phenyl phosphate (7 g,0.025 mol) and 300mL of toluene are added into a 2L reaction bottle equipped with a mechanical stirrer, a thermocouple and a condenser, the reaction temperature is controlled to be-20 ℃, and the mixture is stirred and reacted for 4 hours under normal pressure (1 bar). After the reaction of S1 is finished, excess 2-methoxypropene is recovered by simple distillation, and then intermediate 3-hydroxyolefine ether 426.8g is obtained, and the calculated yield is 98.4%.
The 2L autoclave was cleaned, dried and sealed at room temperature, and then charged with 0.1MPa of nitrogen gas and maintained for 30min, and the pressure in the autoclave did not decrease, which proved that the sealing property was good. The nitrogen gas was vented, the autoclave was opened, and 3-hydroxyvinyl ether intermediate (300g, 1.76mol) obtained by the S1 reaction, p-toluenesulfonic acid (6g, 0.0348mol), a hydrogenation catalyst 10% palladium calcium sulfate (2.4 g), and 200mL of isopropanol as a solvent were added to the autoclave at a time. After all the materials are added, the autoclave is sealed again, nitrogen is charged and discharged for 3 times, each time under 0.1MPa, the air in the autoclave is replaced by nitrogen, and finally the pressure of the nitrogen in the autoclave is normal pressure. Firstly, starting the autoclave to stir at the rotation speed of 450rpm, then starting external heating, and introducing H after the temperature in the autoclave rises to 30 DEG C 2 And (3) until the pressure in the kettle is 0.1MPa, then adjusting a hydrogen pressure reducing valve, maintaining the reaction pressure stable, and stirring for reaction for 2 hours. After the reaction is finished, stopping stirring, discharging hydrogen, sampling and carrying out GC analysis, and obtaining the conversion rate of the 3-hydroxy vinyl ether intermediate serving as the raw material>99 percent, and the selectivity of the target product 6-methyl-5-octen-2-one is 97.2 percent.
Example 4
The starting materials 3-methyl-2-pentenal (250g, 2.55mol), 2-ethoxypropene (250g, 2.90mol), diethyl zinc (0.035g, 0.0003 mol) as a catalyst, diphenyl phosphate (0.07g, 0.0003 mol) and 350mL of methylene chloride as a solvent were charged into a 2L reaction flask equipped with a mechanical stirrer, a thermocouple and a condenser, and the reaction temperature was controlled at 30 ℃ and stirred at normal pressure (1 bar) for 3 hours. After the reaction of S1 is finished, excess 2-methoxypropene is recovered by simple distillation, and then intermediate 3-hydroxyolefine ether 460.02g is obtained, and the calculated yield is 98.0%.
Cleaning and drying a 2L high-pressure autoclave at room temperature, sealing, charging 2MPa nitrogen, maintaining the pressure for 30min, and ensuring good sealing property without reducing the pressure in the high-pressure autoclave. The autoclave was vented, and the 3-hydroxyvinyl ether intermediate (300g, 1.63mol) obtained by the S1 reaction, p-toluenesulfonic acid (0.3g, 0.0017mol), hydrogenation catalyst 0.5% palladium calcium sulfate (4.5 g) and 250mL of ethanol solvent were added to the autoclave in one portion. After all the materials are added, the autoclave is sealed again, nitrogen is charged and discharged for 3 times, each time under 0.5MPa, the air in the autoclave is replaced by nitrogen, and finally the pressure of the nitrogen in the autoclave is normal pressure. Firstly, starting the autoclave to stir at the rotation speed of 450rpm, then starting external heating, and introducing H after the temperature in the autoclave is raised to 35 DEG C 2 And (5) until the pressure in the kettle reaches 2MPa, then adjusting a hydrogen pressure reducing valve, maintaining the reaction pressure stable, and stirring for reaction for 0.5h. After the reaction is finished, stopping stirring, discharging hydrogen, sampling and carrying out GC analysis, and obtaining the conversion rate of the 3-hydroxy vinyl ether intermediate serving as the raw material>99 percent, and the selectivity of the target product 6-methyl-5-octen-2-one is 97.5 percent.
Example 5
Raw materials of 3-methyl-2-pentenal (250g, 2.55mol), 2-propoxypropene (300g, 3.00mol), catalyst of diisopropyl zinc (3g, 0.0198mol), dimethyl phosphate (2.5g, 0.0198mol) and 300mL of n-hexane are added into a 2L reaction bottle equipped with a mechanical stirrer, a thermocouple and a condenser, the reaction temperature is controlled at 0 ℃, and the reaction is stirred under normal pressure (1 bar) for 2 hours. After the reaction of S1 is finished, excess 2-methoxypropene is recovered by simple distillation, and then intermediate 3-hydroxyolefine ether 447.54g is obtained, and the calculated yield is 88.6%.
And (3) cleaning and drying a 2L high-pressure kettle at room temperature, sealing, filling 1MPa nitrogen, maintaining the pressure for 30min, and ensuring that the pressure in the high-pressure kettle is not reduced, thereby proving that the sealing property is good. The autoclave was vented and charged at once with the 3-hydroxyenol ether intermediate (300g, 1.51mol) obtained by the S1 reaction, p-toluenesulfonic acid (4g, 0.0232mol), a hydrogenation catalyst, 5% palladium barium sulfate (2.25 g) and the solvent tetrahydrofuran (250 mL). After all the materials are added, the autoclave is sealed again, nitrogen is charged and discharged for 3 times, each time under 0.5MPa, the air in the autoclave is replaced by nitrogen, and finally the pressure of the nitrogen in the autoclave is normal pressure. Firstly, starting the autoclave to stir at the rotation speed of 450rpm, then starting external heating, and introducing H after the temperature in the autoclave rises to 40 DEG C 2 Until the pressure in the kettle reaches 1MPa, then adjusting a hydrogen pressure reducing valve to maintain the reaction pressureAnd stirring to react for 1h. After the reaction is finished, stopping stirring, discharging hydrogen, sampling and carrying out GC analysis, and obtaining the conversion rate of the 3-hydroxy vinyl ether intermediate serving as the raw material>99 percent, and the selectivity of the target product 6-methyl-5-octen-2-one is 94.6 percent.
Example 6
S1 was reacted as in example 5.
The 2L autoclave was cleaned, dried and sealed at room temperature, 1.5MPa nitrogen was charged and the pressure was maintained for 30min, and the pressure in the autoclave did not decrease, demonstrating good sealing. The autoclave was vented and charged once with the 3-hydroxyvinylether intermediate (300g, 1.51mol) obtained by the S1 reaction, 37% hydrochloric acid (2g, 0.0197mol), 5% palladium on carbon (3 g) as a hydrogenation catalyst and 200mL of methyl t-butyl ether as a solvent. After all the materials are added, the autoclave is sealed again, nitrogen is charged and discharged for 3 times, each time under 0.5MPa, the air in the autoclave is replaced by nitrogen, and finally the pressure of the nitrogen in the autoclave is normal pressure. Firstly, starting the autoclave to stir at the rotation speed of 450rpm, then starting external heating, and introducing H after the temperature in the autoclave is raised to 35 DEG C 2 And (4) until the pressure in the kettle is 1.5MPa, then adjusting a hydrogen pressure reducing valve, maintaining the reaction pressure stable, and stirring for reaction for 1 hour. After the reaction, the stirring was stopped and the hydrogen gas was vented, and the sample was analyzed by GC, whereby the conversion of the starting 3-hydroxyvinylether intermediate was 97.7% and the selectivity of the target product 6-methyl-5-octen-2-one was 86.3%.
Example 7
The starting materials 3-methyl-2-pentenal (250g, 2.55mol), 2-butoxypropene (500g, 4.38mol), dimethyl zinc (1.5g, 0.0157mol) and diphenyl phosphate (4 g, 0.0160mol) as catalysts and 300mL of dichloroethane as a solvent were charged into a 2L reaction flask equipped with a mechanical stirrer, a thermocouple and a condenser, and reacted with stirring under normal pressure (1 bar) at a reaction temperature of 25 ℃ for 4 hours. After the reaction of S1 is finished, excess 2-methoxypropene is recovered by simple distillation, and then intermediate 3-hydroxyolefine ether 490.54g is obtained, and the calculated yield is 90.7%.
The 2L autoclave was cleaned, dried and sealed at room temperature, and 1MPa of nitrogen was charged to maintain the pressure for 30min, and the pressure in the autoclave did not decrease, demonstrating good sealing properties. The autoclave was vented and 3-hydroxyvinylether intermediate (300g, 1.41m) from the S1 reaction was added to the autoclave at one timeol), methanesulfonic acid (2g, 0.0208mol), hydrogenation catalyst 3% palladium barium sulfate (5.25 g) and solvent isopropanol 200mL. After all the materials are added, the autoclave is sealed again, nitrogen is charged and discharged for 3 times, each time under 0.5MPa, the air in the autoclave is replaced by nitrogen, and finally the pressure of the nitrogen in the autoclave is normal pressure. Firstly, starting the autoclave to stir at the rotation speed of 450rpm, then starting external heating, and introducing H after the temperature in the autoclave is raised to 40 DEG C 2 And (4) until the pressure in the kettle is 1MPa, then adjusting a hydrogen pressure reducing valve, maintaining the reaction pressure stable, and stirring for reaction for 1 hour. After the reaction is finished, stopping stirring, discharging hydrogen, sampling and carrying out GC analysis, and obtaining the conversion rate of the 3-hydroxy vinyl ether intermediate serving as the raw material>99 percent, and the selectivity of the target product 6-methyl-5-octen-2-one is 94.8 percent.
Example 8
The reaction of S1 was the same as in example 7.
At room temperature, the 2L autoclave was cleaned, dried and sealed, 2MPa nitrogen was charged and the pressure was maintained for 30min, and the pressure in the autoclave did not decrease, demonstrating good sealing. The autoclave was vented and charged at once with the 3-hydroxyvinylether intermediate (300g, 1.41mol) obtained by the S1 reaction, benzenesulfonic acid (3.5g, 0.0219mol), 5% palladium alumina as a hydrogenation catalyst (3 g) and 200mL of n-butanol as a solvent. After all the materials are added, the autoclave is sealed again, nitrogen is charged and discharged for 3 times, the pressure of the nitrogen in the autoclave is changed into nitrogen each time, and finally the pressure of the nitrogen in the autoclave is normal pressure. Firstly, starting the autoclave to stir at the rotation speed of 450rpm, then starting external heating, and introducing H after the temperature in the autoclave is raised to 60 DEG C 2 And (4) until the pressure in the kettle reaches 2MPa, then adjusting a hydrogen pressure reducing valve, maintaining the reaction pressure stable, and stirring for reaction for 1 hour. After the reaction, stirring was stopped and hydrogen was vented, and a sample was taken for GC analysis, whereby the conversion of the starting 3-hydroxyvinylether intermediate was 98.1% and the selectivity to the desired product, 6-methyl-5-octen-2-one, was 87.8%.
Example 9
The starting materials 3-methyl-2-pentenal (250g, 2.55mol), 2-methoxypropene (300g, 4.16mol), zinc dipropyl catalyst (0.5g, 0.0033mol), dibenzyl phosphate (1g, 0.0036 mol) and 300mL of dichloroethane as a solvent were charged into a 2L reaction flask equipped with a mechanical stirrer, a thermocouple and a condenser, and the reaction temperature was controlled to 10 ℃ and stirred at normal pressure (1 bar) for 2.5 hours. After the reaction of S1 is finished, excess 2-methoxypropene is recovered by simple distillation, and then intermediate 3-hydroxyolefine ether 404.63g is obtained, and the calculated yield is 93.3%.
The 2L autoclave was cleaned, dried and sealed at room temperature, and 1MPa of nitrogen was charged to maintain the pressure for 30min, and the pressure in the autoclave did not decrease, demonstrating good sealing properties. The autoclave was vented and charged at once with the 3-hydroxyvinylether intermediate (300g, 1.76mol) obtained by the S1 reaction, p-toluenesulfonic acid (1g, 0.0058mol), hydrogenation catalyst 10% palladium barium sulfate (1.5 g) and 200mL of ethanol solvent. After all the materials are added, the autoclave is sealed again, nitrogen is charged and discharged for 3 times, each time under 0.5MPa, the air in the autoclave is replaced by nitrogen, and finally the pressure of the nitrogen in the autoclave is normal pressure. Firstly, starting the autoclave to stir at the rotation speed of 450rpm, then starting external heating, and introducing H after the temperature in the autoclave is raised to 50 DEG C 2 And (5) until the pressure in the kettle is 1MPa, then adjusting a hydrogen pressure reducing valve, maintaining the reaction pressure stable, and stirring for reaction for 1.2h. After the reaction is finished, stopping stirring, exhausting hydrogen, sampling and carrying out GC analysis, and converting the 3-hydroxy vinyl ether intermediate of the raw material>99 percent, and the selectivity of the target product 6-methyl-5-octen-2-one is 95.1 percent.
Example 10
S1 was reacted as in example 9.
The 2L autoclave was cleaned, dried and sealed at room temperature, and 1MPa of nitrogen was charged to maintain the pressure for 30min, and the pressure in the autoclave did not decrease, demonstrating good sealing properties. The autoclave was vented and charged at once with 3-hydroxyvinylether intermediate (300g, 1.76mol) obtained by the S1 reaction, 98% sulfuric acid (0.5g, 0.0051mol), calcium carbonate (2.25 g) containing 5% by weight of a hydrogenation catalyst palladium, and 300mL of ethanol as a solvent. After all the materials are added, the autoclave is sealed again, nitrogen is charged and discharged for 3 times, each time under 0.5MPa, the air in the autoclave is replaced by nitrogen, and finally the pressure of the nitrogen in the autoclave is normal pressure. Firstly, starting the autoclave to stir at the rotation speed of 450rpm, then starting external heating, and introducing H after the temperature in the autoclave is raised to 45 DEG C 2 And (4) until the pressure in the kettle is 1MPa, then adjusting a hydrogen pressure reducing valve, maintaining the reaction pressure stable, and stirring for reaction for 1 hour. After the reaction is finished, stopping stirring, emptying hydrogen, sampling and carrying out GC analysis,the conversion rate of the 3-hydroxy vinyl ether intermediate of the raw material is 97.3 percent, and the selectivity of the target product 6-methyl-5-octene-2-ketone is 87.5 percent.
Claims (28)
1. A process for the synthesis of 6-methyl-5-octen-2-one by a carbonyl-ene reaction, the process comprising the following reactions:
s1: carrying out carbonyl-ene reaction on 3-methyl-2-pentenal and 2-alkoxy propylene to obtain a 3-hydroxy alkene ether intermediate;
s2: under the action of acid and a hydrogenation catalyst, the 3-hydroxyolefine ether is subjected to dehydration and hydrogenation reaction to obtain 6-methyl-5-octen-2-one;
wherein the catalyst is prepared in situ from organic zinc and phosphate.
2. The process of claim 1, wherein the 2-alkoxypropene is 2-methoxypropene, 2-ethoxypropene, 2-propoxypropene, 2-butoxypropene.
3. The process of claim 2, wherein the 2-alkoxypropene is 2-methoxypropene or 2-ethoxypropene.
4. The process according to claim 2, wherein the molar amount of 2-alkoxypropene is from 100 to 200% of the molar amount of 3-methyl-2-pentenal.
5. The method of claim 1, wherein the organozinc is one or more of dimethylzinc, diethylzinc, dipropylzinc, diisopropylzinc.
6. The method of claim 5, wherein the organozinc is dimethyl zinc or diethyl zinc.
7. The process according to claim 5, wherein the molar amount of organozinc is between 0.01% and 1.0% of the molar amount of 3-methyl-2-pentenal.
8. The method of claim 1, wherein the phosphate is one or more of dimethyl phosphate, diethyl phosphate, diphenyl phosphate, ditolyl phosphate, dibenzyl phosphate, diisooctyl phosphate.
9. The method of claim 8, wherein the phosphate ester is diphenyl phosphate or ditolyl phosphate.
10. The process according to claim 8, wherein the phosphate is used in an amount of 0.01 to 1.0% based on the molar amount of 3-methyl-2-pentenal.
11. The method of claim 1, wherein an aprotic solvent is used in the S1.
12. The method of claim 11, wherein the aprotic solvent is one or more of n-hexane, n-heptane, toluene, xylene, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, dichloromethane, dichloroethane.
13. The method of claim 12, wherein the aprotic solvent is dichloromethane or toluene.
14. The process of claim 1, wherein the reaction of S1 is a batch reaction, a semi-batch reaction, or a continuous reaction.
15. The method of claim 14, wherein the reaction time of S1 is 1 to 4 hours; and/or
The reaction temperature is-20 to 30 ℃; and/or
The reaction pressure was 1bar.
16. The process of claim 1 wherein after the completion of the S1 reaction, excess 2-alkoxypropene is recovered by distillation and then subjected to de-heavy separation to provide the 3-hydroxyenol ether intermediate.
17. The process of claim 1, wherein the 6-methyl-5-octen-2-one is obtained in a one-pot process using an acid and a hydrogenation catalyst in the S2.
18. The method of claim 1, wherein the acid is methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, hydrochloric acid, or sulfuric acid.
19. The method of claim 18, wherein the acid is methanesulfonic acid or p-toluenesulfonic acid.
20. The process according to claim 17, wherein the molar amount of the acid is 0.1 to 2.0% of the molar amount of the 3-hydroxyvinylether.
21. The process of claim 17, wherein the hydrogenation catalyst is 0.5 to 10.0% palladium on carbon, 0.5 to 10.0% palladium on alumina, 0.5 to 10.0% palladium on calcium carbonate, 0.5 to 10.0% palladium on barium sulfate, or 0.5 to 10.0% palladium on calcium sulfate.
22. The process of claim 21, wherein the hydrogenation catalyst is 0.5-10.0% palladium barium sulfate or 0.5-10.0% calcium sulfate.
23. The process of claim 17, wherein the mass of the hydrogenation catalyst is from 0.5% to 2.0% of the mass of the 3-hydroxyvinylether.
24. The process of claim 1, wherein the reaction of S2 is carried out in an autoclave; and/or
The reaction solvent of S2 is methanol, ethanol, propanol, isopropanol, n-butanol, 2-butanol, tert-butanol, tetrahydrofuran and methyl tert-butyl ether; and/or
The hydrogen pressure in the hydrogenation reaction is 0.1-2.0MPa; and/or
The reaction temperature of the S2 is 30-60 ℃, and the reaction time is 0.5-2h.
25. The method of claim 24, wherein the reaction solvent is ethanol, isopropanol, or tetrahydrofuran.
26. The process of claim 24, wherein the hydrogen is continuously fed and the pressure remains constant during the reaction.
27. The process of claim 1, wherein the reaction of the process is
Wherein R is an alkyl group.
28. The method of claim 27, wherein R is methyl, ethyl, propyl, or butyl.
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| EP3323802A1 (en) * | 2016-11-18 | 2018-05-23 | DSM IP Assets B.V. | Novel use of arylphosphoric acid derivatives as catalyst |
| WO2018091624A1 (en) * | 2016-11-18 | 2018-05-24 | Dsm Ip Assets B.V. | Novel use of phenyl phosphinic acid |
| CN111039769A (en) * | 2019-12-18 | 2020-04-21 | 万华化学集团股份有限公司 | Method for synthesizing methylheptenone from methylbutynol |
| EP3541776B1 (en) * | 2016-11-18 | 2020-12-23 | DSM IP Assets B.V. | Novel process for the manufacture of gamma, delta-unsaturated ketones |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3323802A1 (en) * | 2016-11-18 | 2018-05-23 | DSM IP Assets B.V. | Novel use of arylphosphoric acid derivatives as catalyst |
| WO2018091624A1 (en) * | 2016-11-18 | 2018-05-24 | Dsm Ip Assets B.V. | Novel use of phenyl phosphinic acid |
| EP3541776B1 (en) * | 2016-11-18 | 2020-12-23 | DSM IP Assets B.V. | Novel process for the manufacture of gamma, delta-unsaturated ketones |
| CN111039769A (en) * | 2019-12-18 | 2020-04-21 | 万华化学集团股份有限公司 | Method for synthesizing methylheptenone from methylbutynol |
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