Method for synthesizing 2-(3-hydroxypropyl) cyclododecanone

Abstract

The invention provides a method for synthesizing 2-(3-hydroxypropyl) cyclododecanone, which comprises the following steps of: synthesizing cyclododecanone diallyl alcohol by using cyclododecanone as an initial raw material and acetone diallyl alcohol, and performing cracking reaction on the cyclododecanone diallyl alcohol to obtain the 2-(3-hydroxypropyl) cyclododecanone. In the reaction process, a palladium metal compound is added, so that addition products of cyclododecanone and multiple allyl alcohols and self-coupling products of cyclododecanone are effectively reduced, and the effect of inhibiting side reactions is achieved. 2-(3-hydroxypropyl) cyclododecanone is an important intermediate for synthesizing cyclopentadecanolide, solves the problem that raw materials are limited in a synthetic route of musk perfume cyclopentadecanolide, and has the advantages of high atom utilization rate, low raw material cost and the like.

Description

Technical Field

[0001] The present invention relates to the field of organic synthesis, and in particular to a method for synthesizing 2-(3-hydroxypropyl)cyclododecanone. Background Art

[0002] Cyclopentadecanolide is an important macrocyclic musk that not only has the scent of musk, but also has the aroma of ambergris. It has a strong and delicate aroma, but is expensive. It is currently widely used in perfumes, flavors, cosmetics, food, medicine and other fields. The synthesis of cyclopentadecanolide is divided into two methods: ring expansion method and ring closure method. The advantages of the ring expansion method are easy availability of raw materials, high atomic utilization rate and low raw material cost. BASF, Firmenich, IFF and other companies have patent reports. The ring expansion method mainly refers to using cyclododecanone as the starting material, and obtaining the final product through carbon addition, cyclization, oxidation, cracking and reduction. The reaction route is shown below:

[0003]

[0004] Among them, the first step carbonization reaction product 2-(3-hydroxypropyl) cyclododecanone is the key product of this route, which has a huge impact on the overall yield and cost. Patent US3856815 reported the use of cyclododecanone allyl alcohol as a raw material for carbonization and cyclization reactions, emphasizing that the reaction temperature is inconsistent when different initiators are selected; although there are many choices for free radical initiators described in the patent, di-tert-butyl peroxide is proposed to have the best effect, and the embodiments are all initiated by di-tert-butyl peroxide; the reaction process uses an excess of cyclododecanone to control the selectivity of the monoalkylated product, and a dropwise addition method is used; the two-step reaction has the highest separation yield, and the continuous tubular reaction yield is 42%. Patent US4268445 does not use allyl alcohol as a raw material, but uses tert-butyl ether of allyl alcohol, which is easily cleaved into isobutylene and allyl alcohol under acidic conditions. Therefore, after alkylation, cleavage and cyclization can be carried out in the same step reaction, and the highest separation yield of the first step is 84%.

[0005] The existing technology is to use an excess of cyclododecanone to ensure the selectivity of the monosubstituted product, and the main by-products are the addition products of cyclododecanone and multiple allyl alcohols, and the coupling products of cyclododecanone itself. Since cyclododecanone is solid at room temperature and has a high boiling point, excess cyclododecanone makes subsequent separation and purification more difficult. Summary of the invention

[0006] The purpose of the present invention is to provide a method for synthesizing 2-(3-hydroxypropyl)cyclododecanone to improve product selectivity.

[0007] The technical solution of the present invention is as follows:

[0008] A method for synthesizing 2-(3-hydroxypropyl)cyclododecanone, the method comprising:

[0009] (1) Cyclododecanone is used as a starting material and is reacted with acetone diallyl acetal to synthesize cyclododecanone diallyl acetal.

[0010] (2) Dodecanone diallyl acetal is further subjected to a cleavage reaction to obtain 2-(3-hydroxypropyl)cyclododecanone.

[0011]

[0012] In the present invention, the acetone diallyl acetal can be obtained by condensing acetone and allyl alcohol, or by reacting acetone dimethyl acetal and allyl alcohol. Preferably, acetone diallyl acetal is obtained by reacting acetone dimethyl acetal and allyl alcohol:

[0013]

[0014] In the present invention, in the step of synthesizing cyclododecanone diallyl acetal from cyclododecanone and acetone diallyl acetal, the catalyst used includes an acidic catalyst, and the catalyst is preferably a sulfonic acid compound, for example, one or more selected from methylsulfonic acid, ethylsulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid, more preferably p-toluenesulfonic acid; the amount of the acid catalyst used is 0.1-2% of the mass of the cyclododecanone, preferably 0.2-0.5%.

[0015] In the present invention, the molar ratio of cyclododecanone to acetone diallyl acetal is 1:1-1:5, preferably 1:1.1-1:1.5.

[0016] In the present invention, in the step of synthesizing cyclododecanone diallyl acetal from cyclododecanone and acetone diallyl acetal, the reaction temperature is 90-180°C, preferably 100-150°C.

[0017] In the present invention, the cyclododecanone and acetone diallyl acetal are used to synthesize cyclododecanone diallyl acetal, and the cyclododecanone diallyl acetal is heated in the presence of a catalyst to undergo a cleavage reaction to obtain 2-(3-hydroxypropyl) cyclododecanone. The catalyst used in the cleavage reaction includes an acidic catalyst, and the catalyst is preferably a sulfonic acid compound selected from one or more of methylsulfonic acid, ethylsulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid, more preferably p-toluenesulfonic acid; the amount of the acid catalyst is 0.1-2% of the mass of the cyclododecanone, preferably 0.2-0.5%.

[0018] The cracking reaction temperature is 110-200°C, preferably 120-160°C.

[0019] In the present invention, the cyclododecanone and acetone diallyl alcohol acetal are used to synthesize cyclododecanone diallyl alcohol acetal and dodecanone diallyl alcohol acetal, and then 2-(3-hydroxypropyl) cyclododecanone is obtained by cleavage reaction, and reactive distillation or reactive distillation is adopted. The allyl alcohol and acetone generated by the reaction are separated from the system by reactive distillation or reactive distillation, so as to promote the smooth progress of the reaction. The number of plates in reactive distillation is 5-30, preferably 10-20. Preferably, the reflux ratio of reactive distillation is 1-50:1, preferably 3-10:1.

[0020] In the present invention, the addition of a rhodium metal compound during the synthesis of 2-(3-hydroxypropyl)cyclododecanone using cyclododecanone as a starting material can effectively reduce the addition products of cyclododecanone and multiple allyl alcohols, as well as the coupling products of cyclododecanone itself, thereby achieving the effect of inhibiting side reactions;

[0021] In the present invention, the rhodium metal compound is selected from one or more of an inorganic acid salt of rhodium, a carboxylate of rhodium, an acetyl compound of rhodium, and a carbonyl compound of rhodium; preferably, the rhodium metal compound is selected from one or more of rhodium acetate, rhodium nitrate, rhodium sulfate, rhodium bromide, acetylacetonato carbonyl rhodium, tetrarhodium dodecacarbonyl, and hexarhodium hexacarbonyl, more preferably acetylacetonato carbonyl rhodium. The amount of the rhodium metal compound is 0.01-0.2% of the mass of cyclododecanone, preferably 0.02-0.05%.

[0022] The beneficial effects of the present invention are:

[0023] The 2-(3-hydroxypropyl) cyclododecanone prepared in the present application can be used to synthesize cyclopentadecanolide, which solves the problem of limited raw materials in the synthesis route of cyclopentadecanolide, a musk fragrance. The synthesis of cyclopentadecanolide by this method can ensure product selectivity and reduce allyl alcohol addition products and cyclododecanone self-coupling products. The conversion rate of cyclododecanone is high, which reduces the difficulty of subsequent separation and purification. DETAILED DESCRIPTION

[0024] The present invention is described in detail below by examples, but the present invention is not limited to the following examples.

[0025] The gas chromatography test conditions of the present invention are as follows:

[0026] Instrument model: Agilent GC; Chromatographic column: Agilent cyclodex-B (30m×0.25mm×0.25μm); Column temperature: starting temperature 40℃, heating to 100℃ at 5℃ / min, then heating to 200℃ at 10℃ / min, maintaining for 15min; Inlet temperature: 280℃; FID detector temperature: 300℃; Split injection, split ratio 60:1; Injection volume: 2.0μL; H2 flow rate: 40mL / min; Air flow rate: 400mL / min.

[0027] Preparation Example 1

[0028] The distillation tower uses a tripod screw packing with 10 theoretical plates. 1040.8g of acetone dimethyl acetal (10.0mol), 1742.4g of allyl alcohol (30.0mol) and 3.12g of p-toluenesulfonic acid are added to the distillation tower kettle. The tower is operated under an inert gas atmosphere, the tower bottom operating temperature is 90°C, and the reflux ratio is 3:1. The top phase of the distillation tower is methanol. After 24 hours of reaction, the bottom liquid is analyzed by gas chromatography. The conversion rate of acetone dimethyl acetal is 99.8%, and the selectivity of acetone dimethyl acetal is 99.2%. The tower bottom operating temperature is raised to 120°C and the pressure is reduced to 10KPa. The reflux ratio is 3:1. The 102-103°C fraction is collected. The fraction is acetone dimethyl acetal with a purity of 99.5%.

[0029] Example 1

[0030] The distillation tower uses θ ring packing, with 10 theoretical plates. 910.8g (5mol) cyclododecanone, 1170.9g acetone diallyl acetal (7.5mol), 2.73g p-toluenesulfonic acid and 0.27g acetylacetone carbonyl rhodium are added to the distillation tower kettle. The tower is operated under an inert gas atmosphere, with a bottom operating temperature of 120°C and a reflux ratio of 5:1. The top phase of the distillation tower is acetone. After 12 hours of reaction, the bottom liquid is analyzed by gas chromatography, and the conversion rate of cyclododecanone is 99.3%, the selectivity of cyclododecanone diallyl acetal is 85.3%, and the selectivity of 2-(3-hydroxypropyl) cyclododecanone is 9.2%.

[0031] Cyclododecanone diallyl acetal was obtained by column chromatography, and the NMR information was as follows: chemical shift 1.20-1.30 multiplet 18H; chemical shift 1.50-1.60 multiplet 4H; chemical shift 4.00-4.10 doublet 4H; chemical shift 5.25-5.30 doublet 2H; chemical shift 5.40-5.45 doublet 2H; chemical shift 6.00-6.15 doublet 2H; it was determined to be the target structure.

[0032] The operating temperature at the bottom of the tower was raised to 150°C, and the reflux ratio was 5: 1. The main phase produced from the top of the distillation tower was a mixture of acetone, allyl alcohol and acetone diallyl alcohol acetal. After 6 hours of reaction, the bottom liquid was analyzed by gas chromatography, and the conversion rate of cyclododecanone diallyl alcohol acetal was 99.7%, and the selectivity of 2-(3-hydroxypropyl)cyclododecanone was 93.7%.

[0033] 2-(3-Hydroxypropyl)cyclododecanone was obtained by column chromatography, and the NMR information was as follows: chemical shift 1.20-1.35 multiplet 16H; chemical shift 1.40-1.80 multiplet 6H; chemical shift 2.30-2.60 multiplet 3H; chemical shift 3.60-3.70 singlet 1H; chemical shift 3.75-3.85 doublet 2H; it was determined to be the target structure.

[0034] Example 2

[0035] The distillation tower uses θ ring packing, with 15 theoretical plates. 910.8g (5mol) cyclododecanone, 858.7g acetone diallyl acetal (5.5mol), 1.82g p-toluenesulfonic acid and 0.45g rhodium acetate are added to the distillation tower kettle. The tower is operated under an inert gas atmosphere, with a bottom operating temperature of 150°C and a reflux ratio of 3:1. The top phase of the distillation tower is acetone. After 10 hours of reaction, the bottom liquid is analyzed by gas chromatography, and the conversion rate of cyclododecanone is 98.3%, the selectivity of cyclododecanone diallyl acetal is 80.2%, and the selectivity of 2-(3-hydroxypropyl) cyclododecanone is 12.1%.

[0036] The operating temperature at the bottom of the tower was raised to 160°C, and the reflux ratio was 3:1. The main phase produced from the top of the distillation tower was a mixture of acetone, allyl alcohol and acetone diallyl alcohol acetal. After 4 hours of reaction, the bottom liquid was analyzed by gas chromatography, and the conversion rate of cyclododecanone diallyl alcohol acetal was 99.8%, and the selectivity of 2-(3-hydroxypropyl)cyclododecanone was 90.5%.

[0037] Example 3

[0038] The distillation tower uses θ ring packing, with 20 theoretical plates. 910.8g (5mol) cyclododecanone, 1014.8g acetone allyl acetal (6.5mol), 4.54g p-toluenesulfonic acid and 0.91g rhodium acetate are added to the distillation tower kettle. The tower is operated under an inert gas atmosphere, with a bottom operating temperature of 100°C and a reflux ratio of 10:1. The top phase of the distillation tower is acetone. After 16 hours of reaction, the bottom liquid is analyzed by gas chromatography, and the conversion rate of cyclododecanone is 98.5%, the selectivity of cyclododecanone allyl acetal is 84.6%, and the selectivity of 2-(3-hydroxypropyl) cyclododecanone is 8.9%.

[0039] The operating temperature at the bottom of the tower was raised to 120°C, and the reflux ratio was 10: 1. The main phase produced from the top of the distillation tower was a mixture of acetone, allyl alcohol and acetone diallyl alcohol acetal. After 10 hours of reaction, the bottom liquid was analyzed by gas chromatography, and the conversion rate of cyclododecanone diallyl alcohol acetal was 98.1%, and the selectivity of 2-(3-hydroxypropyl)cyclododecanone was 91.3%.

[0040] Example 4

[0041] The distillation tower uses θ ring packing, with 10 theoretical plates. 910.8g (5mol) cyclododecanone, 1561.2g acetone diallyl acetal (10mol), 9.11g p-toluenesulfonic acid and 0.18g tetrarhodium dodecacarbonyl are added to the distillation tower kettle. The tower is operated under an inert gas atmosphere, with a bottom operating temperature of 170°C and a reflux ratio of 5:1. The top phase of the distillation tower is acetone. After 6 hours of reaction, the bottom liquid is analyzed by gas chromatography, and the conversion rate of cyclododecanone is 99.6%, the selectivity of cyclododecanone diallyl acetal is 75.7%, and the selectivity of 2-(3-hydroxypropyl) cyclododecanone is 13.4%.

[0042] The operating temperature at the bottom of the tower was raised to 200°C, and the reflux ratio was 5: 1. The main phase produced from the top of the distillation tower was a mixture of acetone, allyl alcohol and acetone diallyl alcohol acetal. After 3 hours of reaction, the bottom liquid was analyzed by gas chromatography, and the conversion rate of cyclododecanone diallyl alcohol acetal was 99.9%, and the selectivity of 2-(3-hydroxypropyl)cyclododecanone was 87.6%.

[0043] Comparative Example 1

[0044] Cyclododecanone diallyl acetal and 2-(3-hydroxypropyl)cyclododecanone were prepared in the same manner as in Example 1, except that acetylacetonato carbonyl rhodium was not added in the reaction.

[0045] According to the test, the condensation tower bottom liquid had a cyclododecanone conversion rate of 99.2%, a cyclododecanone diallyl acetal selectivity of 65.7%, and a 2-(3-hydroxypropyl)cyclododecanone selectivity of 5.4%.

[0046] According to the test, the conversion rate of cyclododecanone diallyl acetal in the cracking tower bottom liquid was 99.1%, and the selectivity of 2-(3-hydroxypropyl)cyclododecanone was 35.3%.

Claims

1. A method for synthesizing 2-(3-hydroxypropyl)cyclododecanone, the method comprising: (1) Cyclododecanone is used as a starting material and is reacted with acetone diallyl acetal to synthesize cyclododecanone diallyl acetal. (2) Cyclododecanone diallyl acetal is then subjected to a cleavage reaction to obtain 2-(3-hydroxypropyl)cyclododecanone.

2. The method according to claim 1, wherein: In step (1), the catalyst used includes an acidic catalyst, and the catalyst is preferably a sulfonic acid compound, for example, one or more selected from methanesulfonic acid, ethylsulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid, more preferably p-toluenesulfonic acid; the amount of the acid catalyst is 0.1-2% of the mass of cyclododecanone, preferably 0.2-0.5%.

3. The method according to claim 1 or 2, wherein: In step (1), a rhodium metal compound is added, wherein the rhodium metal compound is selected from one or more of an inorganic acid salt of rhodium, a carboxylate of rhodium, an acetyl compound of rhodium, and a carbonyl compound of rhodium; preferably, the rhodium metal compound is selected from one or more of rhodium acetate, rhodium nitrate, rhodium sulfate, rhodium bromide, acetylacetonato carbonyl rhodium, dodecacarbonyl tetrarhodium, and hexadecanecarbonyl hexarhodium, more preferably acetylacetonato carbonyl rhodium; The amount of the rhodium metal compound used is 0.01-0.2% of the mass of cyclododecanone, preferably 0.02-0.05%.

4. The method according to any one of claims 1 to 3, wherein: In step (1), the molar ratio of cyclododecanone to acetone diallyl acetal is 1:1-1:5, preferably 1:1.1-1:1.

5.

5. The method according to any one of claims 1 to 4, wherein: In step (1), the reaction temperature is 90-180°C, preferably 100-150°C.

6. The method according to any one of claims 1 to 5, wherein: In step (1), reactive distillation or reactive rectification is adopted; preferably, the number of reactive distillation plates is 5-30, preferably 10-20, and the reflux ratio of reactive distillation is 1-50:1, preferably 3-10:

1.

7. The method according to any one of claims 1 to 5, wherein: In step (2), the cleavage reaction catalyst includes an acidic catalyst, and the catalyst is preferably a sulfonic acid compound selected from one or more of methanesulfonic acid, ethylsulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid, and more preferably p-toluenesulfonic acid; the amount of the acid catalyst is 0.1-2% by mass of cyclododecanone, preferably 0.2-0.5%.

8. The method according to any one of claims 1 to 7, wherein: In step (2), a rhodium metal compound is added, wherein the rhodium metal compound is selected from one or more of an inorganic acid salt of rhodium, a carboxylate of rhodium, an acetyl compound of rhodium, and a carbonyl compound of rhodium; preferably, the rhodium metal compound is selected from one or more of rhodium acetate, rhodium nitrate, rhodium sulfate, rhodium bromide, acetylacetonato carbonyl rhodium, dodecacarbonyl tetrarhodium, and hexadecanecarbonyl hexarhodium, more preferably acetylacetonato carbonyl rhodium; The amount of the rhodium metal compound used is 0.01-0.2% of the mass of cyclododecanone, preferably 0.02-0.05%.

9. The method according to any one of claims 1 to 8, wherein: In step (2), the cracking reaction is at 110-200°C, preferably 120-160°C.

10. The method according to any one of claims 1 to 9, wherein: In step (2), reactive distillation or reactive rectification is adopted; preferably, the number of reactive distillation plates is 5-30, preferably 10-20, and the reactive distillation reflux ratio is 1-50:1, preferably 3-10:1.

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