A method for synthesizing damascenone from 6-methyl-3-hepten-2-one

Abstract

The application provides a method for synthesizing damascenone from 6-methyl-3-heptene-2-ketone, which comprises the following steps: S1, 6-methyl-3-heptene-2-ketone and a methyl metal reagent are subjected to addition reaction to obtain a 2,6-dimethyl-3-heptene-2-ol intermediate; and S2, the 2,6-dimethyl-3-heptene-2-ol is subjected to hydrogenation reaction to obtain a damascenone product. The synthesis route is short and novel, and the damascenone product is prepared in a simple and efficient manner from 6-methyl-3-heptene-2-ketone which is cheap and easy to obtain through two-step addition and reduction reaction, and the overall yield of the route is high. Compared with the traditional process using 6-methyl-5-heptene-2-ketone, the raw material cost is significantly reduced. In addition, it is found that the addition of a trace amount of tertiary carbonic acid in the hydrogenation reaction liquid can improve the selectivity of the target product damascenone.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of fine chemical and essence and perfume, and particularly relates to a method for synthesizing perfume damascenone by taking cheap and easily available 6-methyl-3-heptene-2-ketone as raw material and through two-step reactions of addition and hydrogenation. BACKGROUND

[0002] Damascenone, also known as dimethyl heptanol, has the scientific name of 2,6-dimethyl-2-heptanol, is a colorless liquid at room temperature, has a boiling point of 170-172°C, a density of 0.82 kg / L, and a refractive index of 1.425. Damascenone has elegant floral fragrance, and the fragrance is similar to that of freesia and narcissus, and is often used for blending of floral essence. Damascenone sold on the market is currently obtained by artificial synthesis, and the synthetic route is shown as follows: 6-methyl-5-heptene-2-ketone is reacted with methyl magnesium chloride to obtain 2,6-dimethyl-5-heptene-2-ol, and then hydrogenation is performed to obtain damascenone (CN101125797A; Chemical Industry Times, 2009, 2, 32-34). Although the route has realized large-scale production, there are still some aspects to be improved, for example, the raw material 6-methyl-5-heptene-2-ketone is obtained by taking acetone as raw material, and through three-step reactions of acetylene, selective hydrogenation and carol rearrangement, and the price is relatively high due to the relatively large number of synthesis steps; in addition, in the hydrogenation process of 2,6-dimethyl-5-heptene-2-ol, according to the currently known literature and patent reports, the catalyst used is a noble metal catalyst, and the reaction process is a batch tank hydrogenation, and the production cost and energy consumption of the hydrogenation reaction are also relatively high. The above two main reasons make it impossible to further reduce the production cost of damascenone, and limit the further popularization and use of damascenone.

[0003]

[0004] In recent years, some other synthetic routes of damascenone have also been reported. For example, patent CN102295525A1 takes 2-methyl-3-butyn-2-ol as raw material, and under the action of cuprous chloride, sodium bicarbonate, triethylamine and other reagents, alkylates with methyl allyl chloride, and then performs intermittent tank hydrogenation with Raney nickel to obtain damascenone product. Although this method avoids the use of methyl Grignard reagent, the cost is reduced, but the catalyst and auxiliary agent used in the alkylation reaction are relatively high.

[0005] In summary, damascone is a very good floral fragrance with elegant and delicate fragrance. The main synthesis route of the product at present is to take 6-methyl-5-heptene-2-ketone as raw material, and to obtain through 2-step reactions of methyl Grignard reagent addition and hydrogenation. The method has the defects of expensive raw material and intermittent process, resulting in high cost of damascone and limiting its popularization and use. In order to prepare damascone product more economically and cheaply, it is urgent to develop a new synthesis route, use cheap and readily available starting material, and realize continuous process, so as to reduce the production cost. SUMMARY

[0006] The purpose of the present application is to provide a method for simply and efficiently synthesizing damascone by taking 6-methyl-3-heptene-2-ketone as raw material. The method takes cheap and readily available 6-methyl-3-heptene-2-ketone as raw material, converts it into 2,6-dimethyl-3-heptene-2-ol intermediate through Grignard reagent addition, and further hydrogenates the intermediate to obtain damascone product. The synthesis route of the present application is novel, takes 6-methyl-3-heptene-2-ketone as raw material, and significantly reduces the cost of raw material. 6-methyl-3-heptene-2-ketone can be obtained by condensation reaction of cheap isovaleraldehyde and acetone, and its market price is much lower than that of 6-methyl-5-heptene-2-ketone. In addition, the continuous hydrogenation of 2,6-dimethyl-3-heptene-2-ol to prepare damascone is realized, the product is used as solvent, a tubular fixed bed and a catalyst are used, and the method has the advantages of high conversion rate, high selectivity, stable operation and the like.

[0007] In order to achieve the above-mentioned purposes and achieve the above-mentioned technical effects, the present application adopts the following technical solutions:

[0008] A method for synthesizing damascone from 6-methyl-3-heptene-2-ketone, specifically comprising:

[0009] S1, addition reaction of 6-methyl-3-heptene-2-ketone and methyl metal reagent to obtain 2,6-dimethyl-3-heptene-2-ol intermediate;

[0010] S2, hydrogenation reaction of 2,6-dimethyl-3-heptene-2-ol to obtain damascone product.

[0011] The synthesis route of damascone in the present application is as follows:

[0012]

[0013] In the present application, the methyl metal reagent in S1 can be but is not limited to methyl magnesium chloride, methyl magnesium bromide, methyl magnesium iodide, dimethyl lithium copper, dimethyl zinc, trimethyl aluminum, methyl lithium, etc., and is preferably methyl magnesium chloride, methyl magnesium bromide, etc. The amount of the methyl metal reagent is 100-150 mol% of the molar amount of 6-methyl-3-heptene-2-ketone.

[0014] In the present application, the S1 reaction is carried out in an aprotic solvent, which can 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, n-hexane, more preferably tetrahydrofuran, diethyl ether, 2-methyltetrahydrofuran; preferably, the amount of the solvent is 1.5-4.0 times the mass of 6-methyl-3-heptene-2-ketone.

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

[0016] In the present application, optionally, after the addition reaction is complete, a quenching agent can be added to quench the reaction, which can be but is not limited to deionized water, an aqueous ammonium chloride solution, an aqueous ammonium phosphate solution, an aqueous acetic acid solution, dilute hydrochloric acid, dilute sulfuric acid, etc.

[0017] In the present application, the reactor in S2 is a stacked bed or a column reactor.

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

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

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

[0021] In the present application, the S2 continuous hydrogenation reaction feed liquid can optionally add a small amount of tertiary carbonic acid, which can be but is not limited to tertiary valeric acid, 2,2,-dimethylbutyric acid, 2,2,-dimethylvaleric acid, 2,2,-dimethylhexanoic acid, 2,2,-dimethylheptanoic acid, 2-ethyl-2-methylbutyric acid, 2,2-diethylbutyric acid, etc., and the molar ratio of 2,6-dimethyl-3-heptene-2-ol and tertiary carbonic acid is 200-1000:1.

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

[0023] 1. The synthesis route of the method is short and novel. 6-methyl-3-heptene-2-ketone, which is cheap and easy to obtain, is used as a raw material. The damascol product is prepared by addition and reduction in two steps, which is simple and efficient. The overall yield of the route is high. Compared with the traditional process using 6-methyl-5-heptene-2-ketone method, the raw material cost of damascol is significantly reduced.

[0024] 2. It is found in the present application that the addition of a small amount of tertiary carbonic acid in 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 application will be described in detail below, but the present application is not limited to the following examples.

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

[0027] Damascol, Beida Zhengyuan, 99%, industrial grade; Alumina supported nickel 30%, alumina supported nickel 20%, medium catalyst; Alumina supported cobalt 10%, alumina supported ruthenium 5%, Xinnuo catalyst; Tert valeric acid, 2,2,-dimethylbutyric acid, 2,2,-dimethylhexanoic acid, 2,2-diethylbutyric acid, Sigma-Aldrich reagent, AR, 98-99%. Ethanol, isopropyl alcohol, tetrahydrofuran, diethyl ether, Aladdin reagent, chromatographic grade.

[0028] Anhydrous tetrahydrofuran, diethyl ether, chromatographic purity, Aladdin reagent. Methylmagnesium chloride, Sia reagent, 2M THF solution; Methylmagnesium bromide, Myreos reagent, 2M THF solution; Dimethylzinc, Aladdin reagent, 1M toluene solution; Dimethyl lithium, Tanjiang reagent, 0.5M tetrahydrofuran solution; Methylmagnesium iodide, Aladdin reagent, 3M ethyl ether solution; Methyl lithium, Aladdin reagent, 1.6M THF solution. Anhydrous ammonium chloride, sodium sulfate, sodium chloride, National Pharmaceutical Reagent, AR. Hydrogen, 99.9%, Wanhua.

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

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

[0031] Example 1

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

[0033] First, a 1 L three-necked flask was placed in ice water, a magnetic stirrer was put in the flask, and a nitrogen inlet, constant-pressure dropping funnel, etc. were linked to the mouth of the flask. The air in the flask was replaced with nitrogen, and then the flask was sequentially charged with solvent tetrahydrofuran (70.0 g), starting material 6-methyl-3-hepten-2-one (46.7 g, 0.37 mol), and stirring was started. After the mixture was uniformly mixed, a clear and transparent solution was obtained. A tetrahydrofuran solution (203.5 mL, 2.0 M) of methyl magnesium chloride was loaded into the constant-pressure dropping funnel and was added to the flask at a uniform speed. The addition rate of the methyl magnesium chloride was controlled so that the reaction solution in the flask was maintained at about 0 °C, with a maximum temperature of no more than 5 °C. The addition was completed within 1 hour, and the reaction solution was light gray and slightly turbid. Stirring was continued for 1 hour, and sample analysis showed that, according to GC detection, the starting material 6-methyl-3-hepten-2-one was substantially completely reacted, with a conversion rate of >99.0%, and the selectivity of the product 2,6-dimethyl-3-hepten-2-ol was >99.0%. A saturated aqueous ammonium chloride solution (50 mL) was added to the reaction solution through the constant-pressure dropping funnel to quench the unreacted Grignard reagent. The reaction solution was first turbid and then gradually became clear and separated into two phases. After work-up, the reaction solution was first placed in a separatory funnel, and the organic phase was washed with a saturated aqueous ammonium chloride solution and a saturated aqueous sodium chloride solution in sequence. The organic phase was dried over anhydrous sodium sulfate, filtered, and distilled to obtain the product 2,6-dimethyl-3-hepten-2-ol. The obtained product 2,6-dimethyl-3-hepten-2-ol was a known compound, and its GC peak time was consistent with that of a standard product. 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] 6-methyl-3-hepten-2-one and Grignard reagent to prepare 2,6-dimethyl-3- hepten-2-ol

[0036] Firstly, a 1L three-necked flask was placed in a low temperature bath, a magnetic stirrer was put in the flask, the mouth of the flask was linked with nitrogen, a constant pressure dropping funnel and so on, the air in the flask was replaced with nitrogen, then the solvent tetrahydrofuran (166.4g), the raw material 6-methyl-3-hepten-2-one (41.6g, 0.33mol) were added into the flask in turn, the stirring was started, and a clear and transparent liquid was obtained after the mixture was mixed uniformly. The tetrahydrofuran solution of methyl magnesium bromide (247.5mL, 2.0M) was loaded into the constant pressure dropping funnel, and was added into the flask at a uniform speed, the dropping speed of the methyl magnesium bromide was controlled, and the reaction liquid in the flask was kept at about -20°C, and the highest temperature was not more than -15°C. The dropping was completed in 1 hour, the reaction liquid was light gray and slightly suspended. The stirring was continued for 3 hours, the sample was analyzed, the GC detection showed that the raw material 6-methyl-3-hepten-2-one was substantially completely reacted, the conversion rate was >99.0%, and the selectivity of the product 2,6-dimethyl-3-hepten-2-ol was >99.0%. The 10% acetic acid aqueous solution (50mL) was added into the reaction liquid through the constant pressure dropping funnel to quench the unreacted Grignard reagent, the reaction liquid was first suspended, then gradually clarified and separated. The post-treatment was carried out, firstly, the reaction liquid was put into a separating funnel, then the organic phase was separated from the water, the organic phase was washed with saturated ammonium chloride aqueous solution and saturated brine in turn, and the organic phase was dried with anhydrous sodium sulfate, then was filtered and distilled to obtain the product 2,6-dimethyl-3-hepten-2-ol.

[0037] Example 3

[0038] 6-methyl-3-hepten-2-one and dimethyl zinc reagent to prepare 2,6-dimethyl-3- hepten-2-ol

[0039] Firstly, a 1L three-necked flask was placed in ice water, a magnetic stirrer was put in the flask, the mouth of the flask was linked with nitrogen, constant pressure dropping funnel, etc. The air in the three-necked flask was replaced with nitrogen, then solvent diethyl ether (103.4g), raw material 6-methyl-3-hepten-2-one (51.7g, 0.41mol) were sequentially added into the three-necked flask, the stirring was started, and the mixture was uniformly mixed to obtain a clear and transparent liquid. Dimethylzinc toluene solution (451.0mL, 1.0M) was loaded into the constant pressure dropping funnel, and was added into the three-necked flask at a uniform speed. The dropping speed of the dimethylzinc solution was controlled, and the reaction liquid in the three-necked flask was kept at about 0°C, and the highest temperature was not more than 5°C. The addition was completed within 1 hour, and the reaction liquid was light gray and slightly suspended. The reaction liquid was warmed to 40°C, and the stirring was continued for 2 hours. The sample analysis showed that, by GC detection, the raw material 6-methyl-3-hepten-2-one was substantially completely reacted, the conversion rate was >99.0%, and the selectivity of the product 2,6-dimethyl-3-hepten-2-ol was >99.0%. Saturated ammonium chloride aqueous solution (50mL) was added into the reaction liquid through the constant pressure dropping funnel to quench the unreacted dimethylzinc reagent. The reaction liquid first became suspended, and then gradually became clear and separated. After the post-treatment, the reaction liquid was first put into a separatory funnel, the oil and water were separated, then the saturated ammonium chloride aqueous solution and saturated brine were sequentially used to wash the organic phase. After the organic phase was dried with anhydrous sodium sulfate, it was filtered and distilled to obtain the product 2,6-dimethyl-3-hepten-2-ol.

[0040] Example 4

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

[0042] Firstly, a 1L three-necked flask was placed in ice water, a magnetic stirrer was put in the flask, the mouth of the flask was linked with nitrogen, constant pressure dropping funnel, etc. The air in the flask was replaced with nitrogen, then the solvent tetrahydrofuran (60.0g), the raw material 6-methyl-3-hepten-2-one (24.0g, 0.19mol) were added into the flask in turn, the stirring was started, and the mixture was mixed uniformly to obtain a clear and transparent liquid. The dimethyl lithium copper tetrahydrofuran solution (380.0mL, 0.5M) was loaded into the constant pressure dropping funnel, and was added into the flask at a uniform speed. The dropping speed of the dimethyl lithium copper was controlled, and the reaction liquid in the flask was kept at about 0°C, and the highest temperature was not more than 5°C. The addition was completed in 1 hour, and the reaction liquid was light gray and slightly suspended. The reaction liquid was warmed to 40°C, and the stirring was continued for 3 hours. The sample analysis showed that the raw material 6-methyl-3-hepten-2-one was substantially completely reacted, the conversion rate was 98.0%, and the selectivity of the product 2,6-dimethyl-3-hepten-2-ol was 98.8% according to the GC detection. The saturated ammonium chloride aqueous solution (50mL) was added into the reaction liquid through the constant pressure dropping funnel to quench the unreacted dimethyl lithium copper reagent. The reaction liquid became suspended first, and then gradually clear and separated. The post-treatment was carried out. Firstly, the reaction liquid was put into a separating funnel, and the organic phase was separated from the water. The organic phase was washed with the saturated ammonium chloride aqueous solution and the saturated brine in turn, and was dried with anhydrous sodium sulfate. After filtration and distillation, the product 2,6-dimethyl-3-hepten-2-ol was obtained.

[0043] Example 5

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

[0045] Firstly, a 1 L three-necked flask was placed in ice water, a magnetic stirrer was put in the flask, the mouth of the flask was linked with nitrogen, a constant pressure dropping funnel, etc. The air in the flask was replaced with nitrogen, then solvent diethyl ether (102.3 g), raw material 6-methyl-3-hepten-2-one (34.1 g, 0.27 mol) were sequentially added into the flask, stirring was started, and a clear and transparent liquid was obtained after mixing. The ethyl ether solution of methyl magnesium iodide (108.0 mL, 3.0 M) was loaded into the constant pressure dropping funnel, and was added into the flask at a constant speed. The dropping speed of the methyl magnesium iodide was controlled, and the reaction liquid in the flask was kept at about 0°C, and the highest temperature was not more than 5°C. The addition was completed in 1 hour, and the reaction liquid was light gray and slightly suspended. The reaction was continuously stirred for 2 hours, and sample analysis was performed. GC detection showed that the raw material 6-methyl-3-hepten-2-one was substantially completely reacted, the conversion rate was >99.0%, and the selectivity of the product 2,6-dimethyl-3-hepten-2-ol was >99.0%. The 20% ammonium acetate aqueous solution (40 mL) was added into the reaction liquid through the constant pressure dropping funnel to quench the Grignard reagent which was not reacted, and the reaction liquid was first suspended, then gradually clarified and separated. After the post-treatment, the reaction liquid was first put into a separating funnel, then the organic phase was separated from the water, and the organic phase was washed with saturated ammonium chloride aqueous solution and saturated brine in sequence. After the organic phase was dried with anhydrous sodium sulfate, it was filtered and distilled to obtain the product 2,6-dimethyl-3-hepten-2-ol.

[0046] Example 6

[0047] Preparation of 2,6-dimethyl-3-hepten-2-ol by reacting 6-methyl-3-hepten-2-one with methyl lithium reagent

[0048] Firstly, a 1 L three-necked flask was placed in ice water, a magnetic stirrer was put in the flask, and a nitrogen inlet, a constant pressure dropping funnel and the like were linked to the mouth of the flask. The air in the flask was replaced with nitrogen, and then the solvent tetrahydrofuran (150.2 g), the raw material 6-methyl-3-hepten-2-one (42.9 g, 0.34 mol) were sequentially added to the flask. After stirring and mixing, a clear and transparent liquid was obtained. The methyl lithium ethyl ether solution (318.7 mL, 1.6 M) was loaded into the constant pressure dropping funnel and was added to the flask at a constant speed. The dropping speed of the methyl lithium solution was controlled so that the temperature of the reaction liquid in the flask was kept at about 0°C, and the highest temperature was not more than 5°C. The addition was completed in 1 hour. The reaction liquid was light gray and slightly suspended. The stirring was continued for 3 hours. The sample analysis showed that the raw material 6-methyl-3-hepten-2-one was substantially completely reacted, the conversion rate was >99.0%, and the selectivity of the product 2,6-dimethyl-3-hepten-2-ol was >99.0% (determined by GC). The saturated ammonium chloride aqueous solution (60 mL) was added to the reaction liquid through the constant pressure dropping funnel to quench the unreacted methyl lithium reagent. The reaction liquid first became suspended, and then gradually became clear and separated into two phases. After the post-treatment, the reaction liquid was first put into a separatory funnel. After the oil and water were separated, the saturated ammonium chloride aqueous solution and the saturated brine were sequentially used to wash the organic phase. After the organic phase was dried by anhydrous sodium sulfate, it was filtered and distilled to obtain the product 2,6-dimethyl-3-hepten-2-ol.

[0049] Example 7

[0050] Synthesis of damascenone by hydrogenation of 2,6-dimethyl-3-hepten-2-ol catalyzed by aluminum oxide supported nickel-30%

[0051] Firstly, the feed liquid was prepared. The damascenone (132.3 g), 2,6-dimethyl-3-hepten-2-ol (44.1 g, 0.31 mol) and tertiary amyl acid (32 mg, 0.3 mmol) were sequentially added to a wide-mouth flask. After all the materials were added, the wide-mouth flask was placed in a magnetic stirrer and was fully stirred and mixed to obtain a clear, transparent and uniform feed liquid. The continuous hydrogenation reaction was carried out in a tubular reactor. The length of the reaction tube was 60 cm, the inner diameter was 2.5 cm, the middle part of the reaction tube was filled with the aluminum oxide supported nickel-30% catalyst (100 g), and the uppermost and lowermost ends of the reaction tube were filled with ceramic ball packing for fixing and supporting the resin catalyst. The middle part of the reaction tube was a temperature measuring line which was uniformly distributed on the upper and lower parts and had a total of four temperature measuring points. After the catalyst was filled, the power of the fixed bed reactor was turned on, and the feed tank was added with the feed liquid prepared in the foregoing. The circulation oil bath of the reaction tube jacket was turned on, the temperature of the reaction tube was increased to 80°C, and after the temperature was stabilized, the feed laminar pump was turned on. The feed liquid entered the tubular reactor at a speed of 3.3 g / min, and the liquid flowed from the lower end to the upper end. The weight hourly space velocity was 2.0 h-1, and the reaction was carried out under the pressure of 4 MPa. After the reaction was completed, the reaction tube was taken out, and the product was collected. The product was analyzed by GC, and the results showed that the conversion rate of 2,6-dimethyl-3-hepten-2-ol was >99.0%, and the selectivity of damascenone was >99.0%. -1Simultaneously, hydrogen feed was started with a feed rate of 131.1 mL / min and an in-tube pressure of 2.0 MPaG. The feed rate and temperature were kept constant, and continuous reaction was started. After the reaction liquid exited the tube, it was cooled by a condenser and then entered a reaction liquid collection tank. A sampler was installed on the connecting line between the condenser and the collection tank. After the reaction ran smoothly, samples were taken at the sampler at regular intervals. The internal standard n-octane was added to the withdrawn reaction liquid, which was then analyzed by GC. The results showed that the conversion of the raw material 2,6-dimethyl-3-hepten-2-ol was 99.3% and the selectivity of damasconic alcohol was 99.6%. + Calcd for C9H 20 O: 144.1514, found 144.1513.

[0052] Example 8

[0053] Alumina-supported nickel-30% catalyzed hydrogenation of 2,6-dimethyl-3-hepten-2-ol to synthesize damasconic alcohol

[0054] First, the feed liquid was prepared. A jar was sequentially charged with damasconic alcohol (184.9 g), 2,6-dimethyl-3-hepten-2-ol (37.0 g, 0.26 mol), and t-valeric acid (133 mg, 1.3 mmol). After all the materials were added, the jar was placed in a magnetic stirrer and stirred to obtain a clear, transparent, and uniform feed liquid. A continuous hydrogenation reaction was carried out in a tubular reactor. The reactor tube had a length of 60 cm and an inner diameter of 2.5 cm. The middle part of the reactor tube was filled with an alumina-supported nickel-30% catalyst (100 g). The uppermost and lowermost ends of the reactor tube were filled with ceramic ball packing to fix and support the resin catalyst. The middle part of the reactor tube was a temperature measuring line, which was evenly distributed at the upper and lower ends and had a total of four temperature measuring points. After the catalyst was filled, the power supply of the fixed bed reactor was turned on, and the previously prepared feed liquid was added to the feed tank. The reactor tube jacket circulating oil bath was turned on, and the temperature of the reactor tube was increased to 80°C. After the temperature stabilized, the feed laminar pump was turned on, and the feed liquid entered the tubular reactor at a rate of 5.0 g / min. The liquid flowed from the bottom to the top of the reactor tube. The weight hourly space velocity was 3.0 h -1 Simultaneously, hydrogen feed was started with a feed rate of 131.1 mL / min and an in-tube pressure of 2.0 MPaG. The feed rate and temperature were kept constant, and continuous reaction was started. After the reaction liquid exited the tube, it was cooled by a condenser and then entered a reaction liquid collection tank. A sampler was installed on the connecting line between the condenser and the collection tank. After the reaction ran smoothly, samples were taken at the sampler at regular intervals. The internal standard n-octane was added to the withdrawn reaction liquid, which was then analyzed by GC. The results showed that the conversion of the raw material 2,6-dimethyl-3-hepten-2-ol was 99.3% and the selectivity of damasconic alcohol was 99.6%.

[0055] Example 9

[0056] Alumina supported nickel-30% catalyzed hydrogenation of 2,6-dimethyl-3-hepten-2-ol to damascenone

[0057] Firstly, the feed liquid was prepared. Damascenone (256.0 g), 2,6-dimethyl-3-hepten-2-ol (25.6 g, 0.18 mol) and tert-amyl acid (37 mg, 0.4 mmol) were sequentially added into a jar, and after all the materials were added, the jar was placed in a magnetic stirrer for stirring to obtain a clear, transparent and uniform feed liquid. The continuous hydrogenation reaction was carried out in a tubular reactor with a length of 60 cm and an inner diameter of 2.5 cm. The middle part of the reaction tube was filled with alumina supported nickel-30% catalyst (100 g), and the upper and lower ends of the reaction tube were filled with ceramic ball packing for fixing and supporting the resin catalyst. The middle part of the reaction tube was a temperature measuring line, which was uniformly distributed at the upper and lower ends, and there were a total of four temperature measuring points. After the catalyst was filled, the power of the fixed bed reactor was turned on, and the feed tank was added with the prepared feed liquid. The circulation oil bath of the reaction tube was turned on, and the temperature of the reaction tube was increased to 110°C. After the temperature was stable, the feed laminar pump was turned on, and the feed liquid entered the tubular reactor at a speed of 10.0 g / min, with a downflow and upflow, a weight hourly space velocity of 6.0 h -1 -1, and a hydrogen feed speed of 71.6 mL / min and a pressure of 4.0 MPaG in the tube. The feed speed and temperature were kept constant, and the continuous reaction was started. After the reaction liquid exited the reaction tube, it was cooled by a condenser and then entered the reaction liquid collection tank. A sampler was arranged on the connecting pipeline between the condenser and the collection tank. After the reaction was stable, samples were taken at the sampler at regular intervals. The internal standard n-octane was added to the taken reaction liquid, and then GC chromatographic analysis was performed. The results showed that the conversion rate of the raw material 2,6-dimethyl-3-hepten-2-ol was 99.7%, and the selectivity of damascenone was 99.5%.

[0058] Example 10

[0059] Alumina supported nickel-30% catalyzed hydrogenation of 2,6-dimethyl-3-hepten-2-ol to damascenone

[0060] Firstly, the feed liquid was prepared. The ethanol (210.5 g), 2,6-dimethyl-3-hepten-2-ol (52.6 g, 0.37 mol) and 2,2-dimethylbutyric acid (129 mg, 1.1 mmol) were sequentially added into a jar, and after all the materials were added, the jar was placed in a magnetic stirrer for stirring to obtain a clear, transparent and uniform feed liquid. The continuous hydrogenation reaction was carried out in a tubular reactor with a length of 60 cm and an inner diameter of 2.5 cm. The middle part of the reactor was filled with 10% cobalt catalyst supported on alumina (100 g), and the upper and lower ends of the reactor were filled with ceramic ball fillers for fixing and supporting the resin catalyst. The middle part of the reactor was a temperature measuring line with four evenly distributed temperature measuring points. After the catalyst was filled, the power of the fixed bed reactor was turned on, and the prepared feed liquid was added into the feed tank. The circulation oil bath of the reactor was turned on, and the temperature of the reactor was increased to 60°C. After the temperature was stable, the feed flow pump was turned on, and the feed liquid entered the tubular reactor at a speed of 2.5 g / min, with a downflow and upflow mode, and a weight hourly space velocity of 1.5 h -1 -1. The hydrogen feed was also started at a speed of 314.8 mL / min, and the pressure in the tube was 0.5 MPaG. The feed speed and temperature were kept constant, and the continuous reaction was started. After the reaction liquid exited the reactor, it was cooled by a condenser and then entered the reaction liquid collection tank. A sampler was installed on the pipeline connecting the condenser and the collection tank. After the reaction was stable, samples were taken at the sampler at regular intervals. The internal standard n-octane was added to the collected reaction liquid, and then GC chromatography was used for analysis. The results showed that the conversion rate of the raw material 2,6-dimethyl-3-hepten-2-ol was 99.3%, and the selectivity of damasconic alcohol was 99.6%.

[0061] Example 11

[0062] Silicon oxide supported nickel-20% catalytic hydrogenation of 2,6-dimethyl-3-hepten-2-ol to synthesize damasconic alcohol

[0063] First, the feed solution was prepared by sequentially adding isopropanol (196.3 g), 2,6-dimethyl-3-hepten-2-ol (65.4 g, 0.46 mol), and 2,2-dimethylhexanoic acid (332 mg, 2.3 mmol) to a wide-mouth bottle. After all materials were added, a magnetic stir bar was placed in the wide-mouth bottle, and the mixture was stirred thoroughly until homogeneous, resulting in a clear, transparent, and uniform feed solution. A continuous hydrogenation reaction was carried out in a tubular reactor. The reactor tube was 60 cm long and 2.5 cm in inner diameter. The middle section of the reactor tube was filled with alumina-supported nickel-20% catalyst (120 g), while the top and bottom ends were filled with ceramic ball packing material to fix and support the resin catalyst. Temperature measuring lines were evenly distributed throughout the reactor tube, with a total of four temperature measuring points. After the catalyst was filled, the power to the fixed-bed reactor was turned on, and the previously prepared feed solution was added to the feed tank. Turn on the circulating oil bath in the reaction tube jacket to raise the temperature of the reaction tube to 60℃. After the temperature stabilizes, turn on the feed horizontal flow pump and feed the liquid into the tubular reactor at a rate of 1.0 g / min, with bottom inlet and top outlet, and a weight hourly space velocity (WHSV) of 0.5 h⁻¹. -1 Simultaneously, hydrogen feed was initiated at a rate of 39.3 mL / min and an internal pressure of 2.0 MPaG. The feed rate and temperature were kept constant to begin a continuous reaction. After exiting the reaction tube, the reaction solution was cooled by a condenser and then entered a reaction solution collection tank. A sampler was installed on the connection line between the condenser and the collection tank. Once the reaction was running smoothly, samples were periodically taken from the sampler. The extracted reaction solution was mixed with the internal standard n-octane and analyzed by GC chromatography. The results showed a 99.2% conversion rate of the starting material 2,6-dimethyl-3-hepten-2-ol and a 98.7% selectivity for damasmol.

[0064] Example 12

[0065] Alumina-supported ruthenium-5% catalysis for the hydrogenation of 2,6-dimethyl-3-hepten-2-ol to damamol

[0066] Firstly, the feed liquid was prepared. The jar was added with tetrahydrofuran (204.8 g), 2,6-dimethyl-3-hepten-2-ol (51.2 g, 0.36 mol) and 2,2-diethylbutyric acid (208 mg, 1.4 mmol) in sequence. After all the materials were added, the jar was placed in a magnetic stirrer, stirred thoroughly and mixed uniformly to obtain a clear, transparent and uniform feed liquid. The continuous hydrogenation reaction was carried out in a tubular reactor. The length of the reaction tube was 60 cm and the inner diameter was 2.5 cm. The middle part of the reaction tube was filled with 5% ruthenium catalyst supported on alumina (100 g). The upper end and the lower end of the reaction tube were filled with ceramic ball packing for fixing and supporting the resin catalyst. The middle part of the reaction tube was a temperature measuring line, which was uniformly distributed at the upper and lower parts and had a total of four temperature measuring points. After the catalyst was filled, the power of the fixed bed reactor was turned on, and the feed tank was added with the prepared feed liquid. The circulation oil bath of the reaction tube was turned on, and the temperature of the reaction tube was increased to 40°C. After the temperature was stable, the feed laminar pump was turned on, and the feed liquid entered the tubular reactor at a speed of 5.0 g / min. The liquid flowed from bottom to top, and the weight hourly space velocity was 3.0 h -1 -1. At the same time, the hydrogen feed was started, and the feed speed was 62.9 mL / min. The pressure in the tube was 5.0 MPaG. The feed speed and temperature were kept constant, and the continuous reaction was started. After the reaction liquid flowed out of the reaction tube, it was cooled by a condenser and then entered the reaction liquid collection tank. A sampler was arranged on the pipeline connecting the condenser and the collection tank. After the reaction was stable, samples were taken at the sampler at regular time intervals. The internal standard n-octane was added to the taken reaction liquid, and then GC chromatographic analysis was carried out. The results showed that the conversion rate of the raw material 2,6-dimethyl-3-hepten-2-ol was 99.0%, and the selectivity of damasconic alcohol was 99.4%.

Claims

1. A method for synthesizing damarol from 6-methyl-3-hepten-2-one, comprising the following steps: S1, 6-methyl-3-hepten-2-one and methyl metal reagent addition reaction to produce 2,6-dimethyl-3-hepten-2-ol intermediate; S2, 2,6-Dimethyl-3-hepten-2-ol hydrogenation reaction yields damarol product; the feed liquid of the S2 continuous hydrogenation reaction is supplemented with tertiary carbonic acid, which is selected from one or more of tertiary valeric 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-hepten-2-ol to tertiary carbonic acid is 200 to 1000:

1.

2. The method as described in claim 1, characterized in that, The methyl metal reagent in S1 is selected from methylmagnesium chloride, methylmagnesium bromide, methylmagnesium iodide, dimethylcopper lithium, dimethylzinc, trimethylaluminum, and methyllithium; the amount of the methyl metal reagent is 100-150 mol of the molar amount of 6-methyl-3-hepten-2-one.

3. The method as described in claim 1, characterized in that, The S1 reaction is carried out in an aprotic solvent 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; the amount of solvent used is 1.5 to 4.0 times the mass of 6-methyl-3-hepten-2-one.

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

5. The method according to any one of claims 1-3, characterized in that, After the addition reaction is complete, a quencher is added to quench the reaction. The quencher is selected from deionized water, ammonium chloride aqueous solution, ammonium phosphate aqueous solution, acetic acid aqueous solution, dilute hydrochloric acid, and dilute sulfuric acid.

6. The method according to any one of claims 1-3, characterized in that, The reactor in S2 is either a bed reactor or a tubular reactor.

7. The method according to any one of claims 1-3, characterized in that, The catalyst used in S2 is a solid particulate catalyst, selected from one or more of the following: supported nickel, supported palladium, supported cobalt, supported ruthenium, supported rhodium, supported platinum, supported copper, and supported manganese.

8. The method according to any one of claims 1-3, characterized in that, The hydrogenation reaction temperature in S2 is 40–110°C; and / or the hydrogen pressure is 0.5–5.0 MPaG; and / or hydrogen and 2,6-dimethyl-3-hepten-2-ol are simultaneously and continuously fed and discharged, with a feed molar ratio of 3–20:

1. After exiting the reaction tube, the hydrogen and product are separated by gas-liquid phase separation.

9. The method according to any one of claims 1-3, characterized in that, The feed liquid for the S2 continuous hydrogenation reaction consists of 2,6-dimethyl-3-hepten-2-ol and a solvent. The solvent is selected from one or more of methanol, ethanol, isopropanol, ethyl acetate, toluene, tetrahydrofuran, and damasilyl alcohol. The mass ratio of the solvent to 2,6-dimethyl-3-hepten-2-ol is 3–10:1; the feed mass hourly space velocity is 0.5–6.0 h⁻¹. -1 .

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