Synthesis method of 2-(3-hydroxypropyl)-cyclododecanone

Abstract

The invention provides a synthesis method of 2-(3-hydroxypropyl)-cyclododecanone, which is summarized as follows: under the action of a base catalyst, cyclododecanone and epoxy chloropropane react to obtain 2-epoxypropyl cyclododecanone, and then hydrogenation reduction is performed to obtain the 2-(3-hydroxypropyl)-cyclododecanone. The synthetic route is novel, epoxy chloropropane and other reagents are used for alkylation reaction, epoxypropyl can be efficiently introduced to the cyclododecanone 2 site, compared with allyl alcohol, allyl acetate and other alkylation reagents adopted in a traditional process, the method does not need a free radical initiator, a monoalkylated product can be obtained with high selectivity, and the method is suitable for industrial production. And double alkylation and multi-alkylation byproducts do not exist, so that the reaction yield is remarkably improved. Secondly, 2-(3-hydroxypropyl)-cyclododecanone can be selectively obtained by adopting a hydrogenation method, the reaction yield is high, and the selectivity is good. The method has a good application prospect.

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 2-(3-hydroxypropyl)-cyclododecanone by using cyclododecanone and epichlorohydrin as raw materials through two steps of reactions, namely, alkylation reaction and hydrogenation reduction. Background Art

[0002] Natural musk was originally an aromatic substance derived from musk deer, secreted by the secretory glands in the glandular sacs under the abdomen of male musk deer. It has a deep, warm and lasting aroma, plays an important role in perfumery, and brings people a soft and gentle sensory experience, and the fragrance is lingering and lasting. However, natural animal musk is not only limited in source, but also expensive, and cannot meet people's growing demand. In addition, musk deer are on the verge of extinction, and the modern flavor and fragrance industry has basically stopped using natural musk. In order to make up for the deficiency of natural musk, chemists and fragrance synthesis experts began to synthesize musk fragrances very early. After years of hard work, a series of artificial synthetic musk fragrances have been developed. According to their structure and properties, artificially synthesized musk fragrances can be roughly divided into nitro musk, polycyclic musk, macrocyclic musk, linear musk, etc.; these musk fragrances are widely used in various products: shampoo, detergent, soap, cream and various levels of perfume.

[0003] Nitromusk is banned from use because of its poor biodegradability and increasing amount of residues in nature and the human body (bioaccumulation). The aroma of cyclomusk is more elegant and noble than nitromusk, and some polycyclic musk varieties are very close to the aroma of natural musk, so it has won the fragrance market with its elegant fragrance, low price, temperature and non-discoloration; however, according to the latest research, polycyclic musk is difficult to be metabolized by the human body and has the characteristics of bioaccumulation. Macrocyclic musk is a series of analogues of natural musk, which is environmentally friendly and harmless to the human body, and is closest to natural musk in aroma and fragrance. Cyclopentadecenolide and cyclopentadecenolide are the most representative products in macrocyclic musk. Alicyclic and fatty musk fragrances are often referred to as "linear" musk fragrances. In addition to the characteristics of musk, these fragrances often have fruity and pear aromas, and can affect the fragrance in the top notes. Macrocyclic musk and linear musk are the future development trends.

[0004] 2-(3-Hydroxypropyl)-cyclododecanone is a key intermediate for the synthesis of cyclopentadecalactone. Currently, the main synthetic routes are as follows. The first route is to react cyclododecanone with dimethyl carbonate, introduce ethoxycarbonyl to enhance the acidity of the α position, and the resulting ketoester intermediate can efficiently react with acrolein, and finally reduce the aldehyde group and hydrolyze to remove the ethoxycarbonyl to obtain 2-(3-hydroxypropyl)-cyclododecanone; the overall yield of this method is good, but the atom economy is poor and the synthesis steps are long. The second route is to react cyclododecanone with allyl alcohol under the initiation of a peroxy initiator to obtain 2-(3-hydroxypropyl)-cyclododecanone in one step; although this method has few synthetic steps, it requires the use of a large amount of peroxy initiator, and the reaction yield is very poor, and according to relevant literature reports, it is only about 50% (US3907831, US7098347). There is also a document (CN108203426) reporting the use of allyl ester instead of allyl alcohol to react with cyclododecanone, followed by hydrolysis to obtain 2-(3-hydroxypropyl)-cyclododecanone, the yield is improved, but the effect is not very obvious, and the synthesis steps are increased.

[0005]

[0006] In summary, 2-(3-hydroxypropyl)-cyclododecanone is a key intermediate for the synthesis of macrocyclic musk cyclopentadecalactone and cyclopentadecenolactone. The main synthesis method is to use cyclododecanone as a raw material and undergo an alkylation reaction with allyl alcohol or acrolein. The current synthesis methods either have a long route or a poor yield, and thus have a high cost.

[0007] In order to prepare products such as cyclopentadecalactone and cyclopentadecenolide more economically and cheaply, it is urgent to develop a new 2-(3-hydroxypropyl)-cyclododecanone synthesis route to improve the synthesis yield and reduce production costs. Summary of the invention

[0008] The object of the present invention is to provide a simple synthesis method of 2-(3-hydroxypropyl)-cyclododecanone, using cheap and readily available cyclododecanone and epichlorohydrin as raw materials, and obtaining 2-(3-hydroxypropyl)-cyclododecanone by alkylation and hydrogenation. The synthetic route of the present invention is novel, and epichlorohydrin is used for alkylation reaction, and glycidyl is efficiently introduced at the α position of cyclododecanone. Compared with the alkylating agents such as allyl alcohol and allyl acetate used in traditional processes, the present method does not require a large amount of free radical initiators, and can obtain monoalkylated products with high selectivity, without dialkylation and polyalkylation by-products, and significantly improves yield. Secondly, 2-(3-hydroxypropyl)-cyclododecanone can be selectively obtained by hydrogenation method, and the reaction yield is high and the selectivity is good.

[0009] In order to achieve the above objectives and the above technical effects, the present invention adopts the following technical solutions:

[0010] A method for synthesizing 2-(3-hydroxypropyl)-cyclododecanone, specifically comprising:

[0011] S1, under the action of a base catalyst, cyclododecanone and epichlorohydrin undergo an alkylation reaction to obtain a 2-epoxypropylcyclododecanone intermediate;

[0012] S2, 2-epoxypropylcyclododecanone is hydrogenated and reduced under the action of a hydrogenation catalyst and a Lewis acid catalyst to obtain 2-(3-hydroxypropyl)-cyclododecanone.

[0013] The reaction route is shown below:

[0014]

[0015] In the present invention, in S1, the amount of epichlorohydrin used is 110-150 mol% of cyclododecanone.

[0016] In the present invention, the base catalyst in S1 can be but not limited to one or more of metal hydroxides, metal hydrides, metal carbonates, metal phosphates, amino salts, alkyl alcohol salts, guanidines, amidines, and phosphazenes, preferably metal hydroxides (such as sodium hydroxide, potassium hydroxide), metal hydrides (such as sodium hydride, potassium hydride, calcium hydride), amino salts (such as lithium diisopropylamide solution, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide), sodium alkyl alcohols (such as sodium methoxide, sodium ethoxide, potassium tert-butoxide), phosphazenes (such as phosphazene base P4-tert-butyl, phosphazene base P4-tert-octyl), etc.; preferably, the amount of the base catalyst used is 120-160 mol% of cyclododecanone.

[0017] In the present invention, a polar aprotic solvent is preferably used in S1, which may be but is not limited to diethyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, methyl tert-butyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, toluene, xylene, etc.; the amount of the solvent is preferably 4.0 to 8.0 times the mass of cyclododecanone.

[0018] In the present invention, the reaction time of S1 is 2 to 7 hours; and / or the reaction temperature is -20 to 30°C.

[0019] In the present invention, the S2 hydrogenation catalyst can be a conventional hydrogenation catalyst in the art, such as but not limited to palladium carbon, palladium aluminum oxide, palladium silicon oxide, palladium calcium carbonate, palladium barium sulfate, etc., wherein the palladium content is 2-10wt%, preferably 4-8wt%; preferably, the amount of the hydrogenation catalyst used is 0.5-5.0wt% of the 2-epoxypropylcyclododecanone intermediate.

[0020] In the present invention, the Lewis acid in S2 may be, but is not limited to, tin octoate, lithium chloride, zinc chloride, zinc bromide, magnesium chloride, zinc acetate, scandium trifluoromethanesulfonate, ferric chloride, and the like; preferably, the amount of the Lewis acid used is 0.5-2.0 mol% of 2-epoxypropylcyclododecanone.

[0021] In the present invention, the hydrogen used in the S2 hydrogenation reaction contains a certain proportion of carbon monoxide, preferably the proportion of carbon monoxide to hydrogen is 0.5-5.0 vol%; the pressure of the hydrogenation reaction can be 2.0-6.0 MPa, preferably, the pressure used is 4.0-6.0 MPa.

[0022] In the present invention, the solvent used in the hydrogenation reaction of S2 may be, but is not limited to, tetrahydrofuran, 2-methyltetrahydrofuran, methyl tert-butyl ether, ethylene glycol dimethyl ether, toluene, ethanol, isopropanol, acetone, butanone, ethyl acetate, n-butyl acetate, etc.; the amount of the solvent is preferably 3.0 to 7.0 times the mass of 2-epoxypropylcyclododecanone;

[0023] The S2 reaction time is 2 to 6 hours; and / or the reaction temperature is 80 to 120°C.

[0024] The present invention adopts the above technical solution and has the following positive effects:

[0025] 1. The method adopts a novel synthesis route, uses epichlorohydrin as an alkylating agent, and achieves monoalkylation of cyclododecanone with high selectivity without dialkylation or polyalkylation by-products, thereby significantly improving the synthesis yield of the target product 2-(3-hydroxypropyl)-cyclododecanone, and is expected to reduce the production cost of macrocyclic musk lactone.

[0026] 2. Adding a catalytic amount of a Lewis acid promoter to the hydrogenation reaction and adding a certain amount of carbon monoxide to the hydrogen can effectively control the hydrogenation reduction of 2-epoxypropyl and selectively obtain a primary alcohol product, namely 2-(3-hydroxypropyl)-cyclododecanone; at the same time, the reaction conditions are mild and the product yield is high. DETAILED DESCRIPTION

[0027] The present invention is described in detail below by examples, but the present invention is not limited to the following examples.

[0028] The main raw material information is as follows:

[0029] Cyclododecanone, epichlorohydrin, Wanhua, 99%;

[0030] Sodium hydride and potassium hydride, dispersed in minerals, content 60wt%, Aladdin reagent;

[0031] Potassium tert-butoxide, sodium carbonate, sodium chloride, AR, J&K reagent;

[0032] Glacial acetic acid, AR, Sinopharm reagent;

[0033] Sodium sulfate, AR, Xilong reagent;

[0034] Lithium diisopropylamide solution (2M), lithium bis(trimethylsilyl)amide (2M), J&K reagent;

[0035] Anhydrous tetrahydrofuran, ethylene glycol dimethyl ether, toluene, diethylene glycol dimethyl ether, chromatographic grade, J&K reagent;

[0036] Anhydrous methyl tert-butyl ether, 2-methyltetrahydrofuran, Alfa Aesar, chromatographic grade.

[0037] 5% Pd / C, 5% palladium alumina, 2% palladium silicate; Connor Catalyst;

[0038] Zinc chloride, lithium chloride, zinc acetate, Inokane reagent, purity 99%;

[0039] Scandium trifluoromethanesulfonate, zinc bromide, J&K reagent, purity 98%;

[0040] Ethyl acetate and butyl acetate, chromatographic grade, Sinopharm reagent.

[0041] Hydrogen, 99.9%, Wanhua.

[0042] The gas chromatography test conditions of the present invention are as follows:

[0043] Instrument model: Agilent 7890B; Chromatographic column: Capillary column HP-3 (30m×0.30mm×0.25μm); Initial temperature 80℃, rise to 100℃ at a rate of 5℃ / min; then rise to 220℃ at a rate of 10℃ / min, and maintain 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.

[0044] Embodiment 1:

[0045] Preparation of 2-Epoxypropylcyclododecanone Intermediate from Cyclododecanone and Epichlorohydrin

[0046] At room temperature, a 500mL three-necked flask equipped with a magnetic stirrer is placed in an ice-water bath. After nitrogen replacement, solvent tetrahydrofuran (191.4g), substrate cyclododecanone (38.28g, 0.21mol) and epichlorohydrin (21.37g, 0.231mol) are added to the three-necked flask, and stirring is turned on to dissolve cyclododecanone completely. Then sodium hydride powder (dispersed in minerals, content 60%, 10.08g, 0.252mol) is added to the three-necked flask in batches and repeatedly. During the addition of sodium hydride, the temperature of the reaction solution is kept stable, and the generated hydrogen is discharged through a condenser and a bubbler. After sodium hydride is fully added, the reaction solution is kept at 0°C, and the reaction is continued for 4 hours under rapid stirring. Sampling, GC analysis, substrate cyclododecanone is basically reacted completely.

[0047] Post-treatment: deionized water (20 mL) was added to the reaction solution to quench the reaction, and the solvent tetrahydrofuran in the obtained crude reaction solution was removed by rotary evaporation. Then the obtained crude product was dissolved in ethyl acetate (200 mL), washed twice with dilute acetic acid (10 mL, 1M / L), washed once with saturated sodium bicarbonate aqueous solution (10 mL) and saturated brine (10 mL), and the organic phase was dried over anhydrous sodium sulfate and separated by reduced pressure distillation to obtain 47.45 g of the target 2-epoxypropylcyclododecanone intermediate with a yield of 94.0%. High-resolution mass spectrum of the product HRMS-EI M + calcd C 15 H 26 O2:238.1933, found 238.1934. 1 H NMR (400MHz) δ1.30-2.51(m,23H),2.53(m,1H),2.63(q,1H),2.87(q,1H).

[0048] Embodiment 2:

[0049] Preparation of 2-Epoxypropylcyclododecanone Intermediate from Cyclododecanone and Epichlorohydrin

[0050] At room temperature, a 500mL three-necked flask equipped with a magnetic stirrer is placed in an ice-water bath. After nitrogen replacement, solvent tetrahydrofuran (328.1g), substrate cyclododecanone (54.69g, 0.30mol) and epichlorohydrin (33.31g, 0.36mol) are added to the three-necked flask. Stirring is started to dissolve cyclododecanone completely. Then sodium hydride powder (dispersed in minerals, content 60%, 15.60g, 0.39mol) is added to the three-necked flask in batches and repeatedly. During the addition of sodium hydride, the temperature of the reaction solution is kept stable, and the generated hydrogen is discharged through a condenser and a bubbler. After sodium hydride is fully added, the reaction solution is kept at 0°C, and the reaction is continued for 7 hours under rapid stirring. Sampling, GC analysis, substrate cyclododecanone is basically reacted completely.

[0051] After treatment, deionized water (20 mL) was added to the reaction solution to quench the reaction, and the solvent tetrahydrofuran in the obtained crude reaction solution was removed by rotary evaporation. The crude product was then dissolved in ethyl acetate (200 mL), washed twice with dilute acetic acid (10 mL, 1 M / L), washed once with saturated sodium bicarbonate aqueous solution (10 mL) and saturated brine (10 mL), and the organic phase was dried over anhydrous sodium sulfate and separated by reduced pressure distillation to obtain 68.73 g of the target 2-epoxypropylcyclododecanone intermediate with a yield of 95.3%.

[0052] Embodiment 3:

[0053] Preparation of 2-Epoxypropylcyclododecanone Intermediate from Cyclododecanone and Epichlorohydrin

[0054] At room temperature, a 500mL three-necked flask equipped with a magnetic stirrer was placed in a -20°C low-temperature bath. After nitrogen replacement, solvent tetrahydrofuran (196.9 g), substrate cyclododecanone (49.22 g, 0.27 mol) and epichlorohydrin (37.47 g, 0.405 mol) were added to the three-necked flask. Stirring was started to dissolve cyclododecanone completely. Then sodium hydride powder (dispersed in minerals, content 60%, 17.28 g, 0.432 mol) was added to the three-necked flask in batches and repeatedly. During the sodium hydride addition process, the reaction solution temperature was kept stable, and the generated hydrogen was discharged through a condenser tube and a bubbler. After sodium hydride was fully added, the reaction solution was kept at -20°C, and the reaction was continued for 4 hours under rapid stirring. Sampling, GC analysis, substrate cyclododecanone was basically reacted completely.

[0055] After treatment, deionized water (20 mL) was added to the reaction solution to quench the reaction, and the solvent tetrahydrofuran in the obtained crude reaction solution was removed by rotary evaporation. The crude product was then dissolved in ethyl acetate (200 mL), washed twice with dilute acetic acid (10 mL, 1 M / L), washed once with saturated sodium bicarbonate aqueous solution (10 mL) and saturated brine (10 mL), and the organic phase was dried over anhydrous sodium sulfate and separated by reduced pressure distillation to obtain 63.61 g of the target 2-epoxypropylcyclododecanone intermediate with a yield of 98.0%.

[0056] Embodiment 4:

[0057] Preparation of 2-Epoxypropylcyclododecanone Intermediate from Cyclododecanone and Epichlorohydrin

[0058] At room temperature, a 500mL three-necked flask equipped with a magnetic stirrer was placed in a 10°C cold water bath. After nitrogen replacement, the solvent ethylene glycol dimethyl ether (204.2g), substrate cyclododecanone (25.52g, 0.14mol) and epichlorohydrin (15.54g, 0.168mol) were added to the three-necked flask, stirring was started to completely dissolve the cyclododecanone, and then potassium tert-butoxide (20.42g, 0.182mol) powder was added to the three-necked flask in batches and multiple times. The temperature of the reaction solution was kept stable during the addition of potassium tert-butoxide. After potassium tert-butoxide was completely added, the reaction solution was kept at 10°C and the reaction was continued for 3 hours under rapid stirring. Sampling and GC analysis showed that the substrate cyclododecanone was basically reacted completely.

[0059] After treatment, deionized water (20 mL) was added to the reaction solution to quench the reaction, and the solvent ethylene glycol dimethyl ether in the obtained crude reaction solution was removed by rotary evaporation. The crude product was then dissolved in ethyl acetate (200 mL), washed twice with dilute acetic acid (10 mL, 1 M / L), washed once with saturated sodium bicarbonate aqueous solution (10 mL) and saturated brine (10 mL), and the organic phase was dried over anhydrous sodium sulfate and separated by reduced pressure distillation to obtain 31.50 g of the target 2-epoxypropylcyclododecanone intermediate with a yield of 93.6%.

[0060] Embodiment 5:

[0061] Preparation of 2-Epoxypropylcyclododecanone Intermediate from Cyclododecanone and Epichlorohydrin

[0062] At room temperature, a 500mL three-necked flask equipped with a magnetic stirrer is placed in a 10°C cold water bath. After nitrogen replacement, solvent toluene (209.7g), substrate cyclododecanone (41.93g, 0.23mol) and epichlorohydrin (25.54g, 0.276mol) are added to the three-necked flask. Stirring is started to dissolve cyclododecanone completely. Then, potassium hydride () powder (dispersed in minerals, content 60%, 23.06g, 0.345mol) is added to the three-necked flask in batches and repeatedly. During the addition of potassium hydride, the reaction solution temperature is kept stable, and the generated hydrogen is discharged through a condenser tube and a bubbler. After potassium hydride is fully added, the reaction solution is continued to be kept at 10°C, and the reaction is continued for 3 hours under rapid stirring. Sampling, GC analysis, substrate cyclododecanone basic reaction is complete.

[0063] After treatment, deionized water (20 mL) was added to the reaction solution to quench the reaction, and then washed twice with dilute acetic acid (10 mL, 1 M / L), saturated sodium bicarbonate aqueous solution (10 mL), and saturated brine (10 mL) were each washed once. The organic phase was dried over anhydrous sodium sulfate and separated by reduced pressure distillation to obtain 53.30 g of the target 2-epoxypropylcyclododecanone intermediate with a yield of 96.4%.

[0064] Embodiment 6:

[0065] Preparation of 2-Epoxypropylcyclododecanone Intermediate from Cyclododecanone and Epichlorohydrin

[0066] At room temperature, a 500mL three-necked flask equipped with a magnetic stirrer was placed in an ice-water bath. After nitrogen replacement, solvent diethylene glycol dimethyl ether (207.8g), substrate cyclododecanone (34.64g, 0.19mol) and epichlorohydrin (21.10g, 0.228mol) were added to the three-necked flask, stirring was started to completely dissolve the cyclododecanone, and then a tetrahydrofuran solution of lithium diisopropylamide (0.247mol, 2M) was slowly added to the three-necked flask. After lithium diisopropylamide was completely added, the reaction solution was kept at 0°C and the reaction was continued for 3 hours under rapid stirring. Sampling and GC analysis showed that the substrate cyclododecanone was basically reacted completely.

[0067] After treatment, deionized water (20 mL) was added to the reaction solution to quench the reaction, and the solvent diethylene glycol dimethyl ether in the obtained crude reaction solution was removed by rotary evaporation. The crude product was then dissolved in ethyl acetate (200 mL), washed twice with dilute acetic acid (10 mL, 1 M / L), washed once with saturated sodium bicarbonate aqueous solution (10 mL) and saturated brine (10 mL), and the organic phase was dried over anhydrous sodium sulfate and separated by reduced pressure distillation to obtain 41.43 g of the target 2-epoxypropylcyclododecanone intermediate with a yield of 90.7%.

[0068] Embodiment 7:

[0069] Preparation of 2-Epoxypropylcyclododecanone Intermediate from Cyclododecanone and Epichlorohydrin

[0070] At room temperature, a 500mL three-necked flask equipped with a magnetic stirrer was placed in a -20°C low-temperature bath. After nitrogen replacement, solvent methyl tert-butyl ether (255.2g), substrate cyclododecanone (51.04g, 0.28mol) and epichlorohydrin (31.09g, 0.336mol) were added to the three-necked flask. Stirring was started to completely dissolve the cyclododecanone, and then a tetrahydrofuran solution of lithium bis(trimethylsilyl)amide (0.364mol, 2M) was slowly added to the three-necked flask. After lithium bis(trimethylsilyl)amide was completely added, the reaction solution was kept at -20°C and the reaction was continued for 3 hours under rapid stirring. Sampling and GC analysis showed that the substrate cyclododecanone was basically reacted completely.

[0071] After treatment, deionized water (20 mL) was added to the reaction solution to quench the reaction, and the solvent methyl tert-butyl ether in the obtained crude reaction solution was removed by rotary evaporation. The crude product was then dissolved in ethyl acetate (200 mL), washed twice with dilute acetic acid (10 mL, 1 M / L), washed once with saturated sodium bicarbonate aqueous solution (10 mL) and saturated brine (10 mL), and the organic phase was dried over anhydrous sodium sulfate and separated by reduced pressure distillation to obtain 64.61 g of the target 2-epoxypropylcyclododecanone intermediate with a yield of 96.0%.

[0072] Embodiment 8:

[0073] Preparation of 2-Epoxypropylcyclododecanone Intermediate from Cyclododecanone and Epichlorohydrin

[0074] At room temperature, a 500mL three-necked flask equipped with a magnetic stirrer is placed in an ice-water bath. After nitrogen replacement, solvent 2-methyltetrahydrofuran (246.1g), substrate cyclododecanone (49.22g, 0.27mol) and epichlorohydrin (30.00g, 0.324mol) are added to the three-necked flask. Stirring is started to dissolve cyclododecanone completely. Then, sodium hydride powder (dispersed in minerals, content 60%, 16.20g, 0.405mol) is added to the three-necked flask in batches and repeatedly. During the addition of sodium hydride, the temperature of the reaction solution is kept stable, and the generated hydrogen is discharged through a condenser and a bubbler. After sodium hydride is fully added, the reaction solution is kept at 0°C, and the reaction is continued for 2 hours under rapid stirring. Sampling, GC analysis, substrate cyclododecanone is basically reacted completely.

[0075] After treatment, deionized water (20 mL) was added to the reaction solution to quench the reaction, and the solvent 2-methyltetrahydrofuran in the obtained crude reaction solution was removed by rotary evaporation. The crude product was then dissolved in ethyl acetate (200 mL), washed twice with dilute acetic acid (10 mL, 1 M / L), washed once with saturated sodium bicarbonate aqueous solution (10 mL) and saturated brine (10 mL), and the organic phase was dried over anhydrous sodium sulfate and separated by reduced pressure distillation to obtain 61.79 g of the target 2-epoxypropylcyclododecanone intermediate with a yield of 95.2%.

[0076] Embodiment 9:

[0077] Preparation of 2-(3-hydroxypropyl)-cyclododecanone by hydrogenation of 2-epoxypropylcyclododecanone intermediate

[0078] At room temperature, first add a magnetic stirrer to a 250mL autoclave, then add 2-epoxypropylcyclododecanone intermediate (31.25g, 0.13mol) and solvent tetrahydrofuran (125.0g), catalyst 5% Pd / C (0.62g) in sequence, and finally add Lewis acid auxiliary zinc chloride (90mg, 0.7mmol). After all materials are added, the autoclave is sealed, nitrogen and hydrogen are replaced 3 times respectively, and hydrogen containing 0.5vol% carbon monoxide is charged to control the total pressure in the autoclave to 5.0MPa. The autoclave is placed in an oil bath, stirred, and then heated to 100°C, and the reaction is carried out under heat and pressure for 3 hours. After the reaction is completed, the autoclave is cooled, and the catalyst is filtered and separated for sampling and analysis. The quantitative analysis of the obtained reaction solution adopts gas chromatography, and the conversion rate of 2-epoxypropylcyclododecanone is>99%, and the selectivity of the target product 2-(3-hydroxypropyl)-cyclododecanone is 98.1%. High resolution mass spectrometry HRMS-EI M + calcd C 15 H 28 O2:240.2089, found 240.2087. 1 H NMR(400MHz)δ1.30-2.46(m,25H),3.32(brs,1H),3.50(t,2H).

[0079] Embodiment 10:

[0080] Preparation of 2-(3-hydroxypropyl)-cyclododecanone by hydrogenation of 2-epoxypropylcyclododecanone intermediate

[0081] At room temperature, first add a magnetic stirrer to a 500mL autoclave, then add 2-epoxypropylcyclododecanone intermediate (28.85g, 0.12mol) and solvent tetrahydrofuran (201.9g), catalyst 5% Pd / C (0.15g) in sequence, and finally add Lewis acid auxiliary zinc chloride (160mg, 1.2mmol). After all materials are added, the autoclave is sealed, nitrogen and hydrogen are replaced 3 times respectively, and then hydrogen containing 2.0vol% carbon monoxide is charged to control the total pressure in the autoclave to 6.0MPa. The autoclave is placed in an oil bath, stirred, and then heated to 80°C, and the reaction is carried out under heat and pressure for 6 hours. After the reaction is completed, the autoclave is cooled, and the catalyst is filtered and separated for sampling and analysis. The quantitative analysis of the obtained reaction solution adopts gas chromatography, and the conversion rate of 2-epoxypropylcyclododecanone is>99%, and the selectivity of the target product 2-(3-hydroxypropyl)-cyclododecanone is 99.3%.

[0082] Embodiment 11:

[0083] Preparation of 2-(3-hydroxypropyl)-cyclododecanone by hydrogenation of 2-epoxypropylcyclododecanone intermediate

[0084] At room temperature, first add a magnetic stirrer to a 250mL autoclave, then add 2-epoxypropylcyclododecanone intermediate (33.65g, 0.14mol) and solvent tetrahydrofuran (134.6g), catalyst 5% Pd / C (1.68g), and finally add Lewis acid auxiliary zinc chloride (380mg, 2.8mmol). After all materials are added, the autoclave is sealed, nitrogen and hydrogen are replaced 3 times respectively, and hydrogen containing 1.0vol% carbon monoxide is charged to control the total pressure in the autoclave to 5.0MPa. The autoclave is placed in an oil bath, stirred, and then heated to 120°C, and the reaction is kept warm and pressure-maintained for 2 hours. After the reaction is completed, the autoclave is cooled, and the catalyst is filtered and separated for sampling and analysis. The quantitative analysis of the obtained reaction solution adopts gas chromatography, and the conversion rate of 2-epoxypropylcyclododecanone is>99%, and the selectivity of the target product 2-(3-hydroxypropyl)-cyclododecanone is 98.5%.

[0085] Embodiment 12:

[0086] Preparation of 2-(3-hydroxypropyl)-cyclododecanone by hydrogenation of 2-epoxypropylcyclododecanone intermediate

[0087] At room temperature, first add a magnetic stirrer to a 500mL autoclave, then add 2-epoxypropylcyclododecanone intermediate (40.86g, 0.17mol) and solvent tetrahydrofuran (204.3g), catalyst 5% palladium alumina (0.41g), and finally add Lewis acid auxiliary lithium chloride (140mg, 3.4mmol). After all materials are added, the autoclave is sealed, nitrogen and hydrogen are replaced 3 times respectively, and then hydrogen containing 5.0vol% carbon monoxide is filled to control the total pressure in the autoclave to 5.0MPa. The autoclave is placed in an oil bath, stirred, and then heated to 100°C, and the reaction is kept warm and pressure-maintained for 4 hours. After the reaction is completed, the autoclave is cooled, and the catalyst is filtered and separated and then sampled for analysis. The quantitative analysis of the obtained reaction solution adopts gas chromatography, and the conversion rate of 2-epoxypropylcyclododecanone is>99%, and the selectivity of the target product 2-(3-hydroxypropyl)-cyclododecanone is 99.4%.

[0088] Embodiment 13:

[0089] Preparation of 2-(3-hydroxypropyl)-cyclododecanone by hydrogenation of 2-epoxypropylcyclododecanone intermediate

[0090] At room temperature, first add a magnetic stirrer to a 250mL autoclave, then add 2-epoxypropylcyclododecanone intermediate (38.46g, 0.16mol) and solvent butyl acetate (115.4g), catalyst 2% palladium silicon oxide (1.15g), and finally add Lewis acid auxiliary scandium trifluoromethanesulfonate (1.57g, 3.2mmol). After all materials are added, the autoclave is sealed, nitrogen and hydrogen are replaced 3 times respectively, and then hydrogen containing 1.0vol% carbon monoxide is charged to control the total pressure in the autoclave to 5.0MPa. The autoclave is placed in an oil bath, stirred, and then heated to 100°C, and the reaction is kept warm and pressure-maintained for 4 hours. After the reaction is completed, the autoclave is cooled, and the catalyst is filtered and separated and then sampled for analysis. The quantitative analysis of the obtained reaction solution adopts gas chromatography, and the conversion rate of 2-epoxypropylcyclododecanone is>99%, and the selectivity of the target product 2-(3-hydroxypropyl)-cyclododecanone is 98.5%.

[0091] Embodiment 14:

[0092] Preparation of 2-(3-hydroxypropyl)-cyclododecanone by hydrogenation of 2-epoxypropylcyclododecanone intermediate

[0093] At room temperature, first add a magnetic stirrer to a 250mL autoclave, then add 2-epoxypropylcyclododecanone intermediate (36.06g, 0.15mol) and solvent 2-methyltetrahydrofuran (144.2g), catalyst 5% Pd / C (0.36g), and finally add Lewis acid auxiliary zinc acetate (0.55g, 3.0mmol). After all materials are added, the autoclave is sealed, nitrogen and hydrogen are replaced 3 times respectively, and then hydrogen containing 1.0vol% carbon monoxide is filled to control the total pressure in the autoclave to 5.0MPa. The autoclave is placed in an oil bath, stirred, and then heated to 100°C, and the reaction is kept warm and pressure for 6 hours. After the reaction is completed, the autoclave is cooled, the catalyst is filtered and separated, and then sampled for analysis. The quantitative analysis of the obtained reaction solution adopts gas chromatography, and the conversion rate of 2-epoxypropylcyclododecanone is>99%, and the selectivity of the target product 2-(3-hydroxypropyl)-cyclododecanone is 98.6%.

[0094] Embodiment 15:

[0095] Preparation of 2-(3-hydroxypropyl)-cyclododecanone by hydrogenation of 2-epoxypropylcyclododecanone intermediate

[0096] At room temperature, first add a magnetic stirrer to a 250mL autoclave, then add 2-epoxypropylcyclododecanone intermediate (33.65g, 0.14mol) and solvent methyl tert-butyl ether (134.6g), catalyst 5% Pd / C (0.34g), and finally add Lewis acid auxiliary zinc bromide (0.32g, 1.4mmol). After all materials are added, the autoclave is sealed, nitrogen and hydrogen are replaced 3 times respectively, and then hydrogen containing 1.0vol% carbon monoxide is filled to control the total pressure in the autoclave to 5.0MPa. The autoclave is placed in an oil bath, stirred, and then heated to 100°C, and the reaction is kept warm and pressure for 4 hours. After the reaction is completed, the autoclave is cooled, the catalyst is filtered and separated, and then sampled and analyzed. The quantitative analysis of the obtained reaction solution adopts gas chromatography, and the conversion rate of 2-epoxypropylcyclododecanone is>99%, and the selectivity of the target product 2-(3-hydroxypropyl)-cyclododecanone is 98.7%.

[0097] It is easy to understand that the above embodiments are only examples for clear explanation and do not mean that the present invention is limited thereto. For ordinary technicians in the relevant field, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the implementation methods here. The obvious changes or modifications derived from this are still within the protection scope of the present invention.

Claims

1. A method for synthesizing 2-(3-hydroxypropyl)-cyclododecanone, the method comprising the following steps: S1, under the action of a base catalyst, cyclododecanone and epichlorohydrin react to obtain 2-epoxypropylcyclododecanone; S2, 2-epoxypropylcyclododecanone is hydrogenated and reduced to obtain 2-(3-hydroxypropyl)-cyclododecanone.

2. The method according to claim 1, characterized in that The amount of epichlorohydrin used in S1 is 110-150 mol% of cyclododecanone.

3. The method according to any one of claims 1 to 2, characterized in that: The base catalyst in S1 includes one or more of metal hydroxides, metal hydrides, metal carbonates, metal phosphates, amino salts, sodium alkyl alcohols, guanidines, amidines, and phosphazenes, preferably one or more of metal hydroxides, metal hydrides, amino salts, sodium alkyl alcohols, and phosphazenes; preferably, the base catalyst is used in an amount of 120-160 mol% of cyclododecanone.

4. The method according to any one of claims 1 to 3, characterized in that: The polar aprotic solvent used in S1 includes at least one of diethyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, methyl tert-butyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, toluene and xylene; preferably, the amount of the solvent used is 4.0 to 8.0 times the mass of cyclododecanone.

5. The method according to any one of claims 1 to 4, characterized in that: The S1 reaction time is 2 to 7 hours; and / or the reaction temperature is -20 to 30°C.

6. The method according to claim 1, characterized in that The S2 uses a hydrogenation catalyst, including at least one of palladium carbon, palladium aluminum oxide, palladium silicon oxide, palladium calcium carbonate, and palladium barium sulfate; preferably, the amount of the hydrogenation catalyst is 0.5-5.0wt% of 2-epoxypropylcyclododecanone.

7. The method according to any one of claims 1 and 6, characterized in that Lewis acid needs to be added in the hydrogenation reaction of S2, and the Lewis acid includes at least one of tin octoate, lithium chloride, zinc chloride, zinc bromide, magnesium chloride, zinc acetate, scandium trifluoromethanesulfonate, and ferric chloride; preferably, the amount of the Lewis acid is 0.5-2.0 mol% of 2-epoxypropylcyclododecanone.

8. The method according to any one of claims 1 and 6-7, characterized in that: The hydrogen used in the S2 hydrogenation reaction contains carbon monoxide, preferably, the ratio of carbon monoxide to hydrogen is 0.5-5.0 vol%; Preferably, the pressure of the S2 hydrogenation reaction is 2.0 to 6.0 MPa, preferably 4.0 to 6.0 MPa.

9. The method according to any one of claims 1 and 6-8, characterized in that: The solvent in the S2 hydrogenation reaction includes at least one of tetrahydrofuran, 2-methyltetrahydrofuran, methyl tert-butyl ether, ethylene glycol dimethyl ether, toluene, ethanol, isopropanol, acetone, butanone, ethyl acetate, and n-butyl acetate; Preferably, the amount of the solvent used is 3.0 to 7.0 times the mass of 2-epoxypropylcyclododecanone.

10. The method according to any one of claims 1 and 6-9, characterized in that: The S2 reaction time is 2 to 6 hours; and / or the reaction temperature is 80 to 120°C.

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