Method for synthesizing damascenol from 6-methyl-3-heptene-2-ketone

Abstract

The invention provides a method for synthesizing damascenol from 6-methyl-3-heptene-2-ketone, which comprises the following steps: S1, carrying out addition reaction on 6-methyl-3-heptene-2-ketone and a methyl metal reagent to obtain a 2, 6-dimethyl-3-heptene-2-alcohol intermediate; and S2, carrying out a hydrogenation reaction on the 2, 6-dimethyl-3-heptene-2-alcohol to obtain a damascenol product. The synthesis route is short and novel, 6-methyl-3-heptene-2-ketone which is low in price and easy to obtain serves as the raw material, the damascenol product is simply, conveniently and efficiently prepared through the two-step reaction of addition and reduction, the route is high in overall yield, and compared with a 6-methyl-5-heptene-2-ketone method adopted in a traditional process, the raw material cost is remarkably reduced. In addition, the invention also finds that the selectivity of the target product damascenol can be improved by adding trace tert-carbonic acid into the hydrogenation reaction liquid.

Description

Technical Field

[0001] The invention belongs to the field of fine chemicals and flavors and fragrances, and specifically relates to a method for synthesizing the flavor damascol by using cheap and readily available 6-methyl-3-heptene-2-one as a raw material through two steps of addition and hydrogenation reactions. Background Art

[0002] Damascol, also known as dimethylol, dimethylheptanol, etc., is scientifically named 2,6-dimethyl-2-heptanol. It is a colorless liquid at room temperature, with a boiling point of 170-172°C, a density of 0.82kg / L, and a refractive index of 1.425. Damascol has an elegant floral fragrance similar to that of freesia and freesia, and is often used in the preparation of floral fragrances. The damascol currently sold on the market is obtained by artificial synthesis, and its synthetic route is as follows: first, 6-methyl-5-heptene-2-one and methylmagnesium chloride react to obtain 2,6-dimethyl-5-heptene-2-ol, and then hydrogenate to obtain damascol (CN101125797A; Chemical Industry Times, 2009, 2, 32-34). Although this route has achieved large-scale production, there are still some areas to be improved. For example, the raw material 6-methyl-5-heptene-2-one is obtained from acetone through three steps of acetylation, selective hydrogenation and Carroll rearrangement. Due to the large number of synthesis steps, its price is relatively expensive. Secondly, in the hydrogenation process of 2,6-dimethyl-5-heptene-2-ol, according to currently known literature and patent reports, the catalyst used is a precious metal catalyst, and the reaction process uses intermittent reactor hydrogenation. The production cost and energy consumption of this hydrogenation reaction are also relatively high. The above two main reasons make it impossible to further reduce the production cost of damasic alcohol, which limits the further promotion and use of damasic alcohol.

[0003]

[0004] In recent years, there have been some reports on the synthesis routes of other damasic alcohols. For example, patent CN102295525A1 uses 2-methyl-3-butyn-2-ol as a raw material, and methyl allyl chloride undergoes an alkylation reaction under the action of reagents such as cuprous chloride, sodium bicarbonate, and triethylamine, and then Raney nickel intermittent kettle hydrogenation to obtain the damasic alcohol product. Although this method avoids the use of methyl Grignard reagents and reduces costs, the alkylation reaction uses more catalysts and additives, and the cost is relatively high.

[0005] In summary, damascene alcohol is a very good floral fragrance with an elegant and delicate aroma. At present, the main synthetic route of this product is to use 6-methyl-5-heptene-2-one as raw material, and obtain it through two steps of reaction such as methyl Grignard reagent addition and hydrogenation. This method has the disadvantages of expensive raw materials and process intermittent, resulting in high cost of damascene alcohol, which limits its promotion and use. In order to prepare damascene alcohol products more economically and cheaply, it is urgent to develop a new synthetic route, use cheap and readily available starting materials, realize continuous process, and thus reduce production costs. Summary of the invention

[0006] The object of the present invention is to provide a method for synthesizing damascene alcohol in a simple and efficient manner using 6-methyl-3-heptene-2-one as a raw material, using cheap and readily available 6-methyl-3-heptene-2-one as a raw material, and converting it into a 2,6-dimethyl-3-heptene-2-ol intermediate by addition of a Grignard reagent, and the intermediate is further hydrogenated to obtain a damascene alcohol product. The synthesis route of the present invention is novel, and 6-methyl-3-heptene-2-one is used as a raw material, which significantly reduces the cost of raw materials. 6-methyl-3-heptene-2-one can be obtained by the condensation reaction of cheap isovaleraldehyde and acetone, and its market price is much lower than that of 6-methyl-5-heptene-2-one. In addition, 2,6-dimethyl-3-heptene-2-ol is continuously hydrogenated to prepare damascene alcohol, and the product is used as a solvent, and a tubular fixed bed and a catalyst are used, which has the advantages of high conversion rate, high selectivity, stable operation, etc.

[0007] In order to achieve the above objectives and the above technical effects, the present invention adopts the following technical solutions:

[0008] A method for synthesizing damascol from 6-methyl-3-heptene-2-one, specifically:

[0009] S1, 2,6-dimethyl-3-heptene-2-ol intermediate produced by addition reaction of 6-methyl-3-heptene-2-one and methyl metal reagent;

[0010] S2, 2,6-dimethyl-3-heptene-2-ol is hydrogenated to obtain damascol product.

[0011] The synthesis route of Damascolide of the present invention is shown as follows:

[0012]

[0013] In the present invention, the methyl metal reagent in S1 can be but not limited to methylmagnesium chloride, methylmagnesium bromide, methylmagnesium iodide, dimethylcopper lithium, dimethylzinc, trimethylaluminum, methyllithium, etc., preferably methylmagnesium chloride, methylmagnesium bromide, etc.; the amount of the methyl metal reagent is 100-150 mol% of the molar amount of 6-methyl-3-heptene-2-one.

[0014] In the present invention, the S1 reaction is carried out in an aprotic solvent, and the aprotic solvent may be but is not limited to one or more of diethyl ether, dipropyl ether, dibutyl ether, methyl tert-butyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, toluene, and n-hexane, more preferably tetrahydrofuran, diethyl ether, and 2-methyltetrahydrofuran; preferably, the amount of the solvent used is 1.5 to 4.0 times the mass of 6-methyl-3-heptene-2-one.

[0015] In the present invention, the S1 reaction temperature is -20 to 40°C, preferably 0 to 20°C, and / or the reaction pressure is normal pressure, and the reaction time is 1 to 4 hours.

[0016] In the present invention, optionally, after the addition reaction is complete, a quencher can be added to quench the reaction. The quencher can be, but is not limited to, deionized water, an aqueous solution of ammonium chloride, an aqueous solution of ammonium phosphate, an aqueous solution of acetic acid, dilute hydrochloric acid, dilute sulfuric acid, and the like.

[0017] In the present invention, the reactor in S2 is a stacked bed or a shell-and-tube reactor.

[0018] In the present invention, the catalyst used in S2 is a solid particle catalyst, including but not limited to one or more of loaded nickel, loaded palladium, loaded cobalt, loaded ruthenium, loaded rhodium, loaded platinum, loaded copper, and loaded manganese, preferably alumina-loaded nickel, silicon oxide-loaded nickel, zirconium oxide-loaded nickel, alumina-loaded cobalt, etc.

[0019] In the present invention, the hydrogenation reaction temperature in S2 is 40-110°C, preferably 40-80°C; and / or the reaction hydrogen pressure is 0.5-5.0MPaG, preferably 2.0-4.0MPaG; and / or hydrogen and 2,6-dimethyl-3-heptene-2-ol are continuously fed and discharged simultaneously, with a feed molar ratio of 3-20:1, and the hydrogen and product are separated by gas-liquid phase separation after exiting the reaction tube.

[0020] In the present invention, the S2 continuous hydrogenation reaction feed liquid is composed of 2,6-dimethyl-3-heptene-2-ol and a solvent, and the solvent is selected from one or more of methanol, ethanol, isopropanol, ethyl acetate, toluene, tetrahydrofuran, and damascene alcohol, preferably ethanol, damascene alcohol, and tetrahydrofuran. The mass ratio of the solvent to 2,6-dimethyl-3-heptene-2-ol is preferably 3 to 10:1; the feed mass space velocity is preferably 0.5 to 6.0 h -1 .

[0021] In the present invention, a small amount of tert-carbonic acid may be optionally added to the S2 continuous hydrogenation reaction feed liquid, which may be but is not limited to tert-pentanoic acid, 2,2-dimethylbutyric acid, 2,2-dimethylpentanoic acid, 2,2-dimethylhexanoic acid, 2,2-dimethylheptanoic acid, 2-ethyl-2-methylbutyric acid, 2,2-diethylbutyric acid, etc. The molar ratio of 2,6-dimethyl-3-heptene-2-ol to tert-carbonic acid is 200 to 1000:1.

[0022] The present invention adopts the above technical solution and has the following positive effects:

[0023] 1. The synthesis route of this method is short and novel. It uses cheap and easily available 6-methyl-3-heptene-2-one as a raw material, and obtains the damascene alcohol product simply and efficiently through two-step addition and reduction reactions. The overall yield of the route is high. Compared with the traditional process using 6-methyl-5-heptene-2-one, the cost of damascene alcohol raw materials is significantly reduced.

[0024] 2. The present invention finds that adding a trace amount of tertiary carbonic acid to the hydrogenation reaction liquid can effectively improve the selectivity of the target product damascol and reduce the occurrence of side reactions such as residual raw materials and isomerization. DETAILED DESCRIPTION

[0025] The present invention is described in detail below by examples, but the present invention is not limited to the following examples.

[0026] The main raw material information is as follows:

[0027] Damascohol, Beida Zhengyuan, 99%, industrial grade; 30% nickel on alumina, 20% nickel on alumina, medium catalyst; 10% cobalt on alumina, 5% ruthenium on alumina, Xinuoke catalyst; tert-pentanoic acid, 2,2-dimethylbutyric acid, 2,2-dimethylhexanoic acid, 2,2-diethylbutyric acid, Sigma-Aldrich reagent, AR, 98-99%. Ethanol, isopropanol, tetrahydrofuran, ether, Aladdin reagent, chromatographic grade.

[0028] Anhydrous tetrahydrofuran, ether, chromatographically pure, Aladdin reagent. Methylmagnesium chloride, Xiya reagent, 2M THF solution; methylmagnesium bromide, Myrel reagent, 2M THF solution; dimethylzinc, Aladdin reagent, 1M toluene solution; dimethylcopper lithium, Hongjiang reagent, 0.5M tetrahydrofuran solution; methylmagnesium iodide, Aladdin reagent, 3M ether solution; methyllithium, Aladdin reagent, 1.6M THF solution. Anhydrous ammonium chloride, sodium sulfate, sodium chloride, Sinopharm reagent, AR. Hydrogen, 99.9%, Wanhua.

[0029] The gas chromatography test conditions of the present invention are as follows:

[0030] Instrument model: Agilent 7890B; Chromatographic column: Capillary column HP-3 (30m×0.30mm×0.25μm); Initial temperature 80℃, raised to 100℃ at a rate of 5℃ / min; then raised to 200℃ at a rate of 10℃ / min, maintained for 5.0min; finally raised to 240℃ at a rate of 20℃ / min, maintained for 5.0min. Carrier gas high-purity nitrogen, split ratio 30:1, split flow 42mL / min. Carrier gas saving: 19mL / min, start waiting time 5.0min. Injection temperature 250℃, detector FID, detector temperature 250℃, air flow 350mL / min, hydrogen flow 30mL / min, tail gas flow 60mL / min, injection volume 0.2μL.

[0031] Example 1

[0032] Preparation of 2,6-dimethyl-3-heptene-2-ol by reaction of 6-methyl-3-heptene-2-one with Grignard reagent

[0033] First, place a 1L three-necked flask in ice water, put a magnetic stirrer in the flask, connect the flask mouth to nitrogen, constant pressure dropping funnel, etc., replace the air in the three-necked flask with nitrogen, then add solvent tetrahydrofuran (70.0g) and raw material 6-methyl-3-heptene-2-one (46.7g, 0.37mol) to the three-necked flask in turn, start stirring, and mix well to obtain a clear and transparent liquid. Put a tetrahydrofuran solution of methylmagnesium chloride (203.5mL, 2.0M) into a constant pressure dropping funnel and drop it into the three-necked flask at a uniform speed, control the dropping speed of methylmagnesium chloride, keep the reaction solution in the three-necked flask at about 0°C, and the maximum does not exceed 5°C. The addition was completed within 1 hour, and the reaction solution was light gray and slightly suspended. Continue stirring the reaction for 1 hour, take samples for analysis, and perform GC detection. The raw material 6-methyl-3-heptene-2-one is basically reacted, the conversion rate is >99.0%, and the selectivity of the product 2,6-dimethyl-3-heptene-2-ol is >99.0%. Saturated ammonium chloride aqueous solution (50mL) is added to the reaction solution through a constant pressure dropping funnel to quench the unreacted Grignard reagent. The reaction solution is suspended first, then gradually clarified and separated. For post-treatment, the reaction solution is first placed in a separating funnel. After the oil and water are separated, the organic phase is washed in turn with saturated ammonium chloride aqueous solution and saturated brine. After the organic phase is dried over anhydrous sodium sulfate, the 2,6-dimethyl-3-heptene-2-ol product is obtained by filtration and distillation. The obtained 2,6-dimethyl-3-heptene-2-ol product is a known compound, and the GC peak time is consistent with the standard. The high-resolution mass spectrometry data are as follows: HRMS-EI M + Calcd for C9H 18 O:142.1358, found 142.1360.

[0034] Example 2

[0035] Preparation of 2,6-dimethyl-3-heptene-2-ol by reaction of 6-methyl-3-heptene-2-one with Grignard reagent

[0036] First, place a 1L three-necked flask in a low-temperature bath, put a magnetic stirrer in the flask, connect the flask mouth to nitrogen, constant pressure dropping funnel, etc., replace the air in the three-necked flask with nitrogen, then add solvent tetrahydrofuran (166.4g) and raw material 6-methyl-3-heptene-2-one (41.6g, 0.33mol) to the three-necked flask in turn, start stirring, and mix well to obtain a clear and transparent liquid. Put a tetrahydrofuran solution of methylmagnesium bromide (247.5mL, 2.0M) into a constant pressure dropping funnel and add it dropwise to the three-necked flask at a uniform speed, control the dropping speed of methylmagnesium bromide, keep the reaction solution in the three-necked flask at about -20°C, and do not exceed -15°C. The addition was completed within 1 hour, and the reaction solution was light gray and slightly suspended. Continue stirring the reaction for 3 hours, take samples for analysis, and perform GC detection. The raw material 6-methyl-3-heptene-2-one is basically reacted completely, the conversion rate is >99.0%, and the selectivity of the product 2,6-dimethyl-3-heptene-2-ol is >99.0%. 10% acetic acid aqueous solution (50mL) is added to the reaction solution through a constant pressure dropping funnel to quench the unreacted Grignard reagent. The reaction solution first becomes suspended, and then gradually clarifies and separates phases. For post-treatment, first put the reaction solution into a separating funnel, and after the oil and water phases are separated, the organic phase is washed with saturated ammonium chloride aqueous solution and saturated salt water in turn. After the organic phase is dried over anhydrous sodium sulfate, the 2,6-dimethyl-3-heptene-2-ol product is obtained by filtration and distillation.

[0037] Example 3

[0038] Preparation of 2,6-dimethyl-3-heptene-2-ol by reaction of 6-methyl-3-heptene-2-one with dimethyl zinc reagent

[0039] First, place a 1L three-necked flask in ice water, put a magnetic stirrer in the flask, connect the flask mouth to nitrogen, constant pressure dropping funnel, etc., replace the air in the three-necked flask with nitrogen, then add solvent ether (103.4g) and raw material 6-methyl-3-heptene-2-one (51.7g, 0.41mol) to the three-necked flask in turn, start stirring, and mix well to obtain a clear and transparent liquid. Put the toluene solution of dimethyl zinc (451.0mL, 1.0M) into the constant pressure dropping funnel and add it dropwise to the three-necked flask at a uniform speed. Control the dropping speed of the dimethyl zinc solution to keep the reaction solution in the three-necked flask at about 0°C, and the maximum temperature does not exceed 5°C. The addition was completed within 1 hour, and the reaction solution was light gray and slightly turbid. The reaction solution was heated to 40°C, and the reaction was continued to stir for 2 hours. The raw material 6-methyl-3-heptene-2-one was basically reacted, the conversion rate was >99.0%, and the selectivity of the product 2,6-dimethyl-3-heptene-2-ol was >99.0%. Saturated ammonium chloride aqueous solution (50mL) was added to the reaction solution through a constant pressure dropping funnel to quench the unreacted dimethyl zinc reagent. The reaction solution first became suspended, and then gradually clarified and separated. For post-treatment, the reaction solution was first placed in a separating funnel. After the oil and water phases were separated, the organic phase was washed with saturated ammonium chloride aqueous solution and saturated salt water in turn. After the organic phase was dried over anhydrous sodium sulfate, the 2,6-dimethyl-3-heptene-2-ol product was obtained by filtration and distillation.

[0040] Example 4

[0041] Preparation of 2,6-dimethyl-3-heptene-2-ol by reaction of 6-methyl-3-heptene-2-one with dimethylcopper lithium reagent

[0042] First, place a 1L three-necked flask in ice water, put a magnetic stirrer in the flask, connect the flask mouth to nitrogen, constant pressure dropping funnel, etc., replace the air in the three-necked flask with nitrogen, then add solvent tetrahydrofuran (60.0g) and raw material 6-methyl-3-heptene-2-one (24.0g, 0.19mol) to the three-necked flask in turn, start stirring, and mix well to obtain a clear and transparent liquid. Put dimethyl copper lithium tetrahydrofuran solution (380.0mL, 0.5M) into the constant pressure dropping funnel and drop it into the three-necked flask at a uniform speed, control the dropping speed of dimethyl copper lithium, keep the reaction solution in the three-necked flask at about 0°C, and the maximum does not exceed 5°C. The addition was completed within 1 hour, and the reaction solution was light gray and slightly turbid. The reaction solution was heated to 40°C, and the reaction was continued to stir for 3 hours. The raw material 6-methyl-3-heptene-2-one was basically reacted, with a conversion rate of 98.0%, and the selectivity of the product 2,6-dimethyl-3-heptene-2-ol was 98.8%. Saturated ammonium chloride aqueous solution (50mL) was added to the reaction solution through a constant pressure dropping funnel to quench the unreacted dimethyl copper lithium reagent. The reaction solution first became suspended, and then gradually clarified and separated. After post-treatment, the reaction solution was first placed in a separating funnel. After the oil and water phases were separated, the organic phase was washed with saturated ammonium chloride aqueous solution and saturated salt water in turn. After the organic phase was dried over anhydrous sodium sulfate, the 2,6-dimethyl-3-heptene-2-ol product was obtained by filtration and distillation.

[0043] Example 5

[0044] Preparation of 2,6-dimethyl-3-heptene-2-ol by reaction of 6-methyl-3-heptene-2-one with Grignard reagent

[0045] First, place a 1L three-necked flask in ice water, put a magnetic stirrer in the flask, connect the flask mouth to nitrogen, constant pressure dropping funnel, etc., replace the air in the three-necked flask with nitrogen, then add solvent ether (102.3g) and raw material 6-methyl-3-heptene-2-one (34.1g, 0.27mol) to the three-necked flask in turn, start stirring, and mix well to obtain a clear and transparent liquid. Put the ether solution of methyl magnesium iodide (108.0mL, 3.0M) into the constant pressure dropping funnel and add it dropwise to the three-necked flask at a uniform speed. Control the dropping speed of methyl magnesium iodide to keep the reaction solution in the three-necked flask at about 0°C, and the maximum temperature does not exceed 5°C. The addition was completed within 1 hour, and the reaction solution was light gray and slightly suspended. Continue stirring the reaction for 2 hours, take samples for analysis, and perform GC detection. The raw material 6-methyl-3-heptene-2-one is basically reacted, the conversion rate is >99.0%, and the selectivity of the product 2,6-dimethyl-3-heptene-2-ol is >99.0%. 20% ammonium acetate aqueous solution (40mL) is added to the reaction solution through a constant pressure dropping funnel to quench the unreacted Grignard reagent. The reaction solution first becomes suspended, and then gradually clarifies and separates phases. For post-treatment, first put the reaction solution into a separating funnel, and after the oil and water phases are separated, the organic phase is washed with saturated ammonium chloride aqueous solution and saturated salt water in turn. After the organic phase is dried over anhydrous sodium sulfate, the 2,6-dimethyl-3-heptene-2-ol product is obtained by filtration and distillation.

[0046] Example 6

[0047] Preparation of 2,6-dimethyl-3-heptene-2-ol by reaction of 6-methyl-3-heptene-2-one with methyllithium reagent

[0048] First, place a 1L three-necked flask in ice water, put a magnetic stirrer in the flask, connect the flask mouth to nitrogen, constant pressure dropping funnel, etc., replace the air in the three-necked flask with nitrogen, then add solvent tetrahydrofuran (150.2g) and raw material 6-methyl-3-heptene-2-one (42.9g, 0.34mol) to the three-necked flask in turn, start stirring, and mix well to obtain a clear and transparent liquid. Put the ether solution of methyl lithium (318.7mL, 1.6M) into the constant pressure dropping funnel and drop it into the three-necked flask at a uniform speed. Control the dropping speed of the methyl lithium solution to keep the reaction solution in the three-necked flask at about 0°C, and the maximum temperature does not exceed 5°C. The addition is completed within 1 hour, and the reaction solution is light gray and slightly turbid. Continue stirring the reaction for 3 hours, take samples for analysis, and perform GC detection. The raw material 6-methyl-3-heptene-2-one is basically reacted, the conversion rate is >99.0%, and the selectivity of the product 2,6-dimethyl-3-heptene-2-ol is >99.0%. Saturated ammonium chloride aqueous solution (60mL) is added to the reaction solution through a constant pressure dropping funnel to quench the unreacted methyl lithium reagent. The reaction solution first becomes suspended, and then gradually clarifies and separates phases. For post-treatment, the reaction solution is first placed in a separating funnel. After the oil and water phases are separated, the organic phase is washed with saturated ammonium chloride aqueous solution and saturated salt water in turn. After the organic phase is dried over anhydrous sodium sulfate, the 2,6-dimethyl-3-heptene-2-ol product is obtained by filtering and distilling.

[0049] Example 7

[0050] Hydrogenation of 2,6-dimethyl-3-heptene-2-ol to damascenol over alumina-supported nickel-30% catalyst

[0051] First, prepare the feed liquid. Add damascene alcohol (132.3g), 2,6-dimethyl-3-heptene-2-ol (44.1g, 0.31mol) and tert-pentanoic acid (32mg, 0.3mmol) to the wide-mouth bottle in turn; after all the materials are added, put a magnetic bar into the wide-mouth bottle, stir it thoroughly, mix it evenly, and obtain a clear, transparent and uniform feed liquid. Continuous hydrogenation reaction is carried out in a tubular reactor. The reaction tube used is 60cm long and 2.5cm in inner diameter. The middle part of the reaction tube is filled with alumina-loaded nickel-30% catalyst (100g). The upper and lower ends of the reaction tube are filled with ceramic ball fillers to fix and support the resin catalyst; the middle of the reaction tube is a temperature measuring pipeline, which is evenly distributed up and down, with a total of four temperature measuring points. After the catalyst is filled, turn on the power supply of the fixed bed reactor and add the previously prepared feed liquid into the feed tank. Open the circulating oil bath in the jacket of the reaction tube, raise the temperature of the reaction tube to 80°C, and start the feed advection pump after the temperature stabilizes. The feed liquid enters the tubular reactor at a rate of 3.3 g / min, entering from the bottom and exiting from the top, with a weight hourly space velocity of 2.0 h -1. At the same time, start the hydrogen feed, the feed rate is 131.1mL / min, and the pressure in the tube is 2.0MPaG. Keep the feed rate and temperature constant and start the continuous reaction; after the reaction liquid leaves the reaction tube, it is cooled by the condenser and then enters the reaction liquid collection tank. A sampler is set on the pipeline connecting the condenser and the collection tank. After the reaction runs smoothly, samples are taken at the sampler at regular intervals, and the internal standard n-octane is added to the reaction liquid taken out, and then analyzed by GC chromatography. The results show that the conversion rate of the raw material 2,6-dimethyl-3-heptene-2-ol is 99.3%, and the selectivity of damascarpone is 99.6%. The product damascarpone is a known compound, and the GC peak time is consistent with the standard. The high-resolution mass spectrometry data are as follows: HRMS-EI M + Calcd for C9H 20 O:144.1514, found 144.1513.

[0052] Example 8

[0053] Hydrogenation of 2,6-dimethyl-3-heptene-2-ol to damascenol over alumina-supported nickel-30% catalyst

[0054] First, prepare the feed liquid. Add damascene alcohol (184.9g), 2,6-dimethyl-3-heptene-2-ol (37.0g, 0.26mol) and tert-pentanoic acid (133mg, 1.3mmol) to the wide-mouth bottle in turn; after all the materials are added, put a magnetic bar into the wide-mouth bottle, stir it thoroughly, mix it evenly, and obtain a clear, transparent and uniform feed liquid. Continuous hydrogenation reaction is carried out in a tubular reactor. The reaction tube used is 60cm long and 2.5cm in inner diameter. The middle part of the reaction tube is filled with alumina-loaded nickel-30% catalyst (100g). The upper and lower ends of the reaction tube are filled with ceramic ball fillers to fix and support the resin catalyst; the middle of the reaction tube is a temperature measuring pipeline, which is evenly distributed up and down, with a total of four temperature measuring points. After the catalyst is filled, turn on the power supply of the fixed bed reactor and add the previously prepared feed liquid into the feed tank. Open the circulating oil bath in the jacket of the reaction tube, raise the temperature of the reaction tube to 80°C, and start the feed advection pump after the temperature stabilizes. The feed liquid enters the tubular reactor at a rate of 5.0 g / min, entering from the bottom and exiting from the top, with a weight hourly space velocity of 3.0 h -1 . At the same time, start the hydrogen feed, the feed rate is 52.5mL / min, and the pressure in the tube is 5.0MPaG. Keep the feed rate and temperature constant and start the continuous reaction; after the reaction liquid leaves the reaction tube, it is cooled by the condenser and then enters the reaction liquid collection tank. A sampler is set on the pipeline connecting the condenser and the collection tank. After the reaction runs smoothly, samples are taken at the sampler at regular intervals, and the internal standard n-octane is added to the reaction liquid taken out, and then analyzed by GC chromatography. The results show that the conversion rate of the raw material 2,6-dimethyl-3-heptene-2-ol is 99.5%, and the selectivity of damascarpone is 99.4%.

[0055] Example 9

[0056] Hydrogenation of 2,6-dimethyl-3-heptene-2-ol to damascenol over alumina-supported nickel-30% catalyst

[0057] First, prepare the feed liquid. Add damascene alcohol (256.0g), 2,6-dimethyl-3-heptene-2-ol (25.6g, 0.18mol) and tert-pentanoic acid (37mg, 0.4mmol) to the wide-mouth bottle in turn; after all the materials are added, put a magnetic bar into the wide-mouth bottle, stir it thoroughly, mix it evenly, and obtain a clear, transparent and uniform feed liquid. Continuous hydrogenation reaction is carried out in a tubular reactor. The reaction tube used is 60cm long and 2.5cm in inner diameter. The middle part of the reaction tube is filled with alumina-loaded nickel-30% catalyst (100g). The upper and lower ends of the reaction tube are filled with ceramic ball fillers to fix and support the resin catalyst; the middle of the reaction tube is a temperature measuring pipeline, which is evenly distributed up and down, with a total of four temperature measuring points. After the catalyst is filled, turn on the power supply of the fixed bed reactor and add the previously prepared feed liquid into the feed tank. Open the circulating oil bath in the jacket of the reaction tube, raise the temperature of the reaction tube to 110°C, and start the feed advection pump after the temperature stabilizes. The feed liquid enters the tubular reactor at a rate of 10.0 g / min, entering from the bottom and exiting from the top, with a weight hourly space velocity of 6.0 h -1 . At the same time, start the hydrogen feed, the feed rate is 71.6mL / min, and the pressure in the tube is 4.0MPaG. Keep the feed rate and temperature constant and start the continuous reaction; after the reaction liquid leaves the reaction tube, it is cooled by the condenser and enters the reaction liquid collection tank. A sampler is set on the pipeline connecting the condenser and the collection tank. After the reaction runs smoothly, samples are taken at the sampler at regular intervals, and the internal standard n-octane is added to the reaction liquid taken out, and then analyzed by GC chromatography. The results show that the conversion rate of the raw material 2,6-dimethyl-3-heptene-2-ol is 99.7%, and the selectivity of damascarpone is 99.5%.

[0058] Example 10

[0059] Hydrogenation of 2,6-dimethyl-3-heptene-2-ol to damascenol catalyzed by 10% cobalt supported on alumina

[0060] First, prepare the feed liquid. Add ethanol (210.5g), 2,6-dimethyl-3-heptene-2-ol (52.6g, 0.37mol) and 2,2-dimethylbutyric acid (129mg, 1.1mmol) to the wide-mouth bottle in turn; after all the materials are added, put a magnetic bar into the wide-mouth bottle, stir it thoroughly, mix it evenly, and obtain a clear, transparent and uniform feed liquid. Continuous hydrogenation reaction is carried out in a tubular reactor. The reaction tube used is 60cm long and 2.5cm in inner diameter. The middle part of the reaction tube is filled with alumina-loaded cobalt-10% catalyst (100g). The upper and lower ends of the reaction tube are filled with ceramic ball fillers to fix and support the resin catalyst; the middle of the reaction tube is a temperature measuring pipeline, which is evenly distributed up and down, with a total of four temperature measuring points. After the catalyst is filled, turn on the power supply of the fixed bed reactor and add the previously prepared feed liquid into the feed tank. Open the circulating oil bath in the jacket of the reaction tube, raise the temperature of the reaction tube to 60°C, and start the feed advection pump after the temperature stabilizes. The feed liquid enters the tubular reactor at a rate of 2.5 g / min, entering from the bottom and exiting from the top, with a weight hourly space velocity of 1.5 h -1 . At the same time, start the hydrogen feed, the feed rate is 314.8mL / min, and the pressure in the tube is 0.5MPaG. Keep the feed rate and temperature constant and start the continuous reaction; after the reaction liquid leaves the reaction tube, it is cooled by the condenser and then enters the reaction liquid collection tank. A sampler is set on the pipeline connecting the condenser and the collection tank. After the reaction runs smoothly, samples are taken at the sampler at regular intervals, and the internal standard n-octane is added to the reaction liquid taken out, and then analyzed by GC chromatography. The results show that the conversion rate of the raw material 2,6-dimethyl-3-heptene-2-ol is 99.3%, and the selectivity of damascarpone is 99.6%.

[0061] Embodiment 11

[0062] Hydrogenation of 2,6-dimethyl-3-heptene-2-ol to damascenol catalyzed by nickel-20% supported on silica

[0063] First, prepare the feed liquid. Add isopropanol (196.3g), 2,6-dimethyl-3-heptene-2-ol (65.4g, 0.46mol) and 2,2-dimethylhexanoic acid (332mg, 2.3mmol) to the wide-mouth bottle in turn; after all the materials are added, put a magnetic bar into the wide-mouth bottle, stir it thoroughly, mix it evenly, and obtain a clear, transparent and uniform feed liquid. Continuous hydrogenation reaction is carried out in a tubular reactor. The reaction tube used is 60cm long and 2.5cm in inner diameter. The middle part of the reaction tube is filled with alumina-loaded nickel-20% catalyst (120g). The upper and lower ends of the reaction tube are filled with ceramic ball fillers to fix and support the resin catalyst; the middle of the reaction tube is a temperature measuring pipeline, which is evenly distributed up and down, with a total of four temperature measuring points. After the catalyst is filled, turn on the power supply of the fixed bed reactor and add the previously prepared feed liquid into the feed tank. Open the circulating oil bath in the jacket of the reaction tube, raise the temperature of the reaction tube to 60°C, and start the feed advection pump after the temperature stabilizes. The feed liquid enters the tubular reactor at a rate of 1.0 g / min, entering from the bottom and exiting from the top, with a weight hourly space velocity of 0.5 h -1 . At the same time, start the hydrogen feed, the feed rate is 39.3mL / min, and the pressure in the tube is 2.0MPaG. Keep the feed rate and temperature constant and start the continuous reaction; after the reaction liquid leaves the reaction tube, it is cooled by the condenser and enters the reaction liquid collection tank. A sampler is set on the pipeline connecting the condenser and the collection tank. After the reaction runs smoothly, samples are taken at the sampler at regular intervals, and the internal standard n-octane is added to the reaction liquid taken out, and then analyzed by GC chromatography. The results show that the conversion rate of the raw material 2,6-dimethyl-3-heptene-2-ol is 99.2%, and the selectivity of damascarpone is 98.7%.

[0064] Example 12

[0065] Hydrogenation of 2,6-dimethyl-3-heptene-2-ol to damascenol catalyzed by ruthenium-5% supported on alumina

[0066] First, prepare the feed liquid. Add tetrahydrofuran (204.8g), 2,6-dimethyl-3-heptene-2-ol (51.2g, 0.36mol) and 2,2-diethylbutyric acid (208mg, 1.4mmol) to the wide-mouth bottle in turn. After all the materials are added, put a magnetic bar into the wide-mouth bottle, stir it thoroughly, and mix it evenly to obtain a clear, transparent and uniform feed liquid. Continuous hydrogenation reaction is carried out in a tubular reactor. The reaction tube used is 60cm long and 2.5cm in inner diameter. The middle part of the reaction tube is filled with alumina-supported ruthenium-5% catalyst (100g). The upper and lower ends of the reaction tube are filled with ceramic ball fillers to fix and support the resin catalyst. The middle of the reaction tube is a temperature measuring pipeline, which is evenly distributed up and down, with a total of four temperature measuring points. After the catalyst is filled, turn on the power supply of the fixed bed reactor and add the previously prepared feed liquid into the feed tank. Open the circulating oil bath in the jacket of the reaction tube, raise the temperature of the reaction tube to 40°C, and start the feed advection pump after the temperature stabilizes. The feed liquid enters the tubular reactor at a rate of 5.0 g / min, entering from the bottom and exiting from the top, with a weight hourly space velocity of 3.0 h -1 . At the same time, the hydrogen feed was turned on, the feed rate was 62.9mL / min, and the pressure in the tube was 5.0MPaG. The feed rate and temperature were kept constant to start the continuous reaction; after the reaction liquid exited the reaction tube, it was cooled by the condenser and then entered the reaction liquid collection tank. A sampler was set on the pipeline connecting the condenser and the collection tank. After the reaction ran smoothly, samples were taken at the sampler at regular intervals, and the internal standard n-octane was added to the reaction liquid taken out, and then analyzed by GC chromatography. The results showed that the conversion rate of the raw material 2,6-dimethyl-3-heptene-2-ol was 99.0%, and the selectivity of damascarpone was 99.4%.

Claims

1. A method for synthesizing damascol from 6-methyl-3-heptene-2-one, comprising the following steps: S1, 2,6-dimethyl-3-heptene-2-ol intermediate produced by addition reaction of 6-methyl-3-heptene-2-one and methyl metal reagent; S2, 2,6-dimethyl-3-heptene-2-ol is hydrogenated to obtain damascol product.

2. The method according to claim 1, characterized in that The methyl metal reagent in S1 is selected from methylmagnesium chloride, methylmagnesium bromide, methylmagnesium iodide, dimethylcopper lithium, dimethylzinc, trimethylaluminum, methyllithium, etc., preferably methylmagnesium chloride, methylmagnesium bromide, etc.; the amount of the methyl metal reagent is 100-150 mol% of the molar amount of 6-methyl-3-heptene-2-one.

3. The method according to claim 1 or 2, characterized in that The S1 reaction is carried out in an aprotic solvent, and the aprotic solvent is selected from one or more of diethyl ether, dipropyl ether, dibutyl ether, methyl tert-butyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, toluene, and n-hexane, and tetrahydrofuran, diethyl ether, and 2-methyltetrahydrofuran are more preferred; preferably, the amount of the solvent used is 1.5 to 4.0 times the mass of 6-methyl-3-heptene-2-one.

4. The method according to any one of claims 1 to 3, characterized in that: The S1 reaction temperature is -20 to 40°C, preferably 0 to 20°C, and / or the reaction pressure is normal pressure, and the reaction time is 1 to 4 hours.

5. The method according to any one of claims 1 to 4, characterized in that: Optionally, after the addition reaction is complete, a quencher is added to quench the reaction. The quencher may be, but is not limited to, deionized water, an aqueous solution of ammonium chloride, an aqueous solution of ammonium phosphate, an aqueous solution of acetic acid, dilute hydrochloric acid, dilute sulfuric acid, and the like.

6. The method according to any one of claims 1 to 5, characterized in that: The reactor in S2 is a stacked bed or a shell-and-tube reactor.

7. The method according to any one of claims 1 to 6, characterized in that: The catalyst used in S2 is a solid particle catalyst, including but not limited to one or more of loaded nickel, loaded palladium, loaded cobalt, loaded ruthenium, loaded rhodium, loaded platinum, loaded copper, and loaded manganese, preferably alumina-loaded nickel, silicon oxide-loaded nickel, zirconium oxide-loaded nickel, alumina-loaded cobalt, etc.

8. The method according to any one of claims 1 to 7, characterized in that: The hydrogenation reaction temperature in S2 is 40-110°C, preferably 40-80°C; and / or, the reaction hydrogen pressure is 0.5-5.0MPaG, preferably 2.0-4.0MPaG; and / or, hydrogen and 2,6-dimethyl-3-heptene-2-ol are continuously fed and discharged simultaneously, with a feed molar ratio of 3-20:1, and hydrogen and products are separated by gas-liquid phase separation after exiting the reaction tube.

9. The method according to any one of claims 1 to 8, characterized in that The feed liquid of the S2 continuous hydrogenation reaction is composed of 2,6-dimethyl-3-heptene-2-ol and a solvent, wherein the solvent is selected from one or more of methanol, ethanol, isopropanol, ethyl acetate, toluene, tetrahydrofuran, and damascarpone, preferably ethanol, damascarpone, and tetrahydrofuran, and the mass ratio of the solvent to 2,6-dimethyl-3-heptene-2-ol is preferably 3 to 10:1; the feed mass space velocity is preferably 0.5 to 6.0 h -1 .

10. The method according to any one of claims 1 to 9, characterized in that: The S2 continuous hydrogenation reaction feed liquid can optionally be added with a small amount of tert-carbonic acid, such as one or more of tert-pentanoic acid, 2,2-dimethylbutyric acid, 2,2-dimethylpentanoic acid, 2,2-dimethylhexanoic acid, 2,2-dimethylheptanoic acid, 2-ethyl-2-methylbutyric acid, and 2,2-diethylbutyric acid, and the molar ratio of 2,6-dimethyl-3-heptene-2-ol to tert-carbonic acid is 200 to 1000:1.

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