A method of synthesizing 2-(3-hydroxypropyl)cyclododecanone

Abstract

The application provides a method for synthesizing 2-(3-hydroxypropyl)cyclododecanone, which comprises the following steps: taking cyclododecanone as a starting material, synthesizing cyclododecanone diallyl acetal with diallyl acetal, and then obtaining 2-(3-hydroxypropyl)cyclododecanone through a cleavage reaction. The addition of palladium metal compounds in the reaction process effectively reduces the addition products of cyclododecanone and multiple allyl alcohols, and the coupling products of cyclododecanone itself, so that the effect of inhibiting side reactions is achieved. 2-(3-hydroxypropyl)cyclododecanone is an important intermediate for synthesizing cyclopentadecanolide, solves the problem of limited raw materials in the synthesis route of the musk cyclopentadecanolide, and has the advantages of high atom utilization rate and low raw material cost.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis, and more specifically, to a method for synthesizing 2-(3-hydroxypropyl)cyclododecanone. Background Technology

[0002] Cyclopentadecanolactone is an important macrocyclic musk, possessing not only a musky aroma but also an ambergris-like fragrance. Its aroma is rich and delicate, but it is expensive and currently widely used in perfumes, fragrances, cosmetics, food, and pharmaceuticals. The synthesis of cyclopentadecanolactone involves two methods: ring expansion and ring closure. The ring expansion method has the advantages of readily available raw materials, high atom utilization, and low raw material cost. BASF, Firmenich, and IFF have all reported patents related to this method. The ring expansion method mainly refers to using cyclododecanone as the starting material, proceeding through carbon enrichment, cyclization, oxidation, pyrolysis, and reduction to obtain the final product. The reaction route is illustrated below:

[0003]

[0004] The first-step carbonization reaction product, 2-(3-hydroxypropyl)cyclododecanoate, is a key product in this route, significantly impacting the overall yield and cost. Patent US3856815 reports the use of allyl cyclododecanoate as a starting material for carbonization and cyclization reactions, emphasizing the inconsistent reaction temperatures depending on the initiator used. Although the patent describes many options for free radical initiators, it suggests that di-tert-butyl peroxide is the most effective, and all examples use di-tert-butyl peroxide as the initiator. The reaction process uses excess cyclododecanoate to control the selectivity of the monoalkylation product, employing a dropwise addition method. The highest separation yield for the two-step reaction is 42% for the continuous tubular reaction. Patent US4268445 does not use allyl alcohol as a starting material but instead uses tert-butyl ether of allyl alcohol. This ether readily cleaves into isobutylene and allyl alcohol under acidic conditions; therefore, after alkylation, cleavage and cyclization can occur in the same step, achieving a highest separation yield of 84% for the first step.

[0005] Current technology involves using an excess of cyclododecanone to ensure selectivity for monosubstituted products. The main byproducts are addition products of cyclododecanone with multiple allyl alcohols, as well as coupling products of cyclododecanone itself. Since cyclododecanone is a solid at room temperature and has a high boiling point, excess cyclododecanone poses significant challenges for subsequent separation and purification. Summary of the Invention

[0006] The purpose of this invention is to provide a method for synthesizing 2-(3-hydroxypropyl)cyclododecanone, thereby improving 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) Cyclododecone was used as a starting material to synthesize cyclododecone diallyl alcohol from acetone diallyl alcohol.

[0010] (2) Dodeca-diallyl alcohol is further cleaved to give 2-(3-hydroxypropyl)cyclododeca.

[0011]

[0012] In this invention, the acetone diallyl condensate can be obtained by condensing acetone with allyl alcohol, or by reacting acetone dimethyl condensate with allyl alcohol, preferably by reacting acetone dimethyl condensate with allyl alcohol to obtain acetone diallyl condensate.

[0013]

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

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

[0016] In this invention, the reaction temperature in the step of synthesizing cyclododecanone-diallyl alcohol from cyclododecanone and acetone-diallyl alcohol is 90-180℃, preferably 100-150℃.

[0017] In this invention, cyclododecanone is synthesized from acetone-diallyl alcohol to cyclododecanone-diallyl alcohol. The cyclododecanone-diallyl alcohol, upon heating in the presence of a catalyst, undergoes a further pyrolysis reaction to yield 2-(3-hydroxypropyl)cyclododecanone. The pyrolysis reaction uses an acidic catalyst, preferably a sulfonic acid compound selected from one or more of methanesulfonic acid, ethylsulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid, more preferably p-toluenesulfonic acid. The amount of acidic catalyst used is 0.1-2% of the mass of cyclododecanone, preferably 0.2-0.5%.

[0018] The pyrolysis reaction is carried out at 110-200℃, preferably 120-160℃.

[0019] In this invention, cyclododecanone is reacted with acetone-diallyl alcohol to synthesize cyclododecanone-diallyl alcohol, and then 2-(3-hydroxypropyl)cyclododecanone is obtained by pyrolysis reaction using reactive distillation or reactive rectification. Reactive distillation or reactive rectification separates the allyl alcohol and acetone generated in the reaction from the system, promoting the smooth progress of the reaction. The reactive distillation column has 5-30 plates, preferably 10-20. Preferably, the reactive distillation reflux ratio is 1-50:1, more preferably 3-10:1.

[0020] In this invention, the addition of a rhodium metal compound during the synthesis of 2-(3-hydroxypropyl)cyclododecone from cyclododecone as a starting material can effectively reduce the addition products of cyclododecone with multiple allyl alcohols, as well as the coupling products of cyclododecone itself, thereby achieving the effect of suppressing side reactions.

[0021] In this invention, the rhodium metal compound is selected from one or more of the following: inorganic acid salts of rhodium, carboxylates of rhodium, acetyl compounds of rhodium, and carbonyl compounds of rhodium; preferably, the rhodium metal compound is selected from one or more of the following: rhodium acetate, rhodium nitrate, rhodium sulfate, rhodium bromide, rhodium acetylacetone carbonyl, tetrarhodium dodecyl, and hexadecyl hexarhodium, more preferably rhodium acetylacetone carbonyl. The amount of the rhodium metal compound used is 0.01-0.2% by mass of cyclododecanone, preferably 0.02-0.05%.

[0022] The beneficial effects of this invention are as follows:

[0023] The 2-(3-hydroxypropyl)cyclododecanone prepared in this application can be used to synthesize cyclododecanone lactone, solving the problem of limited raw materials in the synthetic route of cyclododecanone for musk fragrances. This method ensures product selectivity and reduces allyl alcohol addition products and cyclododecanone self-coupling products. The high conversion rate of cyclododecanone reduces the difficulty of subsequent separation and purification. Detailed Implementation

[0024] The present invention is described in detail below through embodiments, but the present invention is not limited to the embodiments described below.

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

[0026] Instrument model: Agilent GC; Column: Agilent Cyclodex-B (30m × 0.25mm × 0.25μm); Column temperature: Initial temperature 40℃, ramped to 100℃ at 5℃ / min, then ramped to 200℃ at 10℃ / min, held for 15min; Injector 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 column was packed with a three-legged spiral packing system with 10 theoretical plates. 1040.8 g of acetone dimethyl condensate (10.0 mol), 1742.4 g of allyl alcohol (30.0 mol), and 3.12 g of p-toluenesulfonic acid were added to the bottom of the distillation column. The operation was carried out under an inert gas atmosphere, with a bottom operating temperature of 90°C and a reflux ratio of 3:1. Methanol was collected from the top of the distillation column. After 24 hours of reaction, gas chromatography analysis of the bottom liquid showed a acetone dimethyl condensate conversion of 99.8% and an allyl alcohol selectivity of 99.2%. The bottom operating temperature was then raised to 120°C and the pressure reduced to 10 kPa, with a reflux ratio of 3:1. The fraction collected at 102-103°C was identified as allyl alcohol condensate with a purity of 99.5%.

[0029] Example 1

[0030] The distillation column used θ-ring packing with 10 theoretical plates. 910.8 g (5 mol) of cyclododecanone, 1170.9 g (7.5 mol) of acetone-diallyl alcohol, 2.73 g of p-toluenesulfonic acid, and 0.27 g of acetylacetone-rhodium carbonyl were added to the bottom of the distillation column. The operation was carried out under an inert gas atmosphere, with a bottom operating temperature of 120℃ and a reflux ratio of 5:1. The top product of the distillation column was acetone. After 12 hours of reaction, gas chromatography analysis of the bottom liquid showed a cyclododecanone conversion of 99.3%, a cyclododecanone-diallyl alcohol selectivity of 85.3%, and a 2-(3-hydroxypropyl)cyclododecanone selectivity of 9.2%.

[0031] Cyclododecanoic acid dienylpropanol was obtained by column chromatography. 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. This was identified as the target structure.

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

[0033] 2-(3-hydroxypropyl)cyclododecanone was obtained by column chromatography. The NMR information was as follows: multiplet at chemical shift 1.20-1.35 16H; multiplet at chemical shift 1.40-1.80 6H; multiplet at chemical shift 2.30-2.60 3H; singlet at chemical shift 3.60-3.70 1H; doublet at chemical shift 3.75-3.85 2H. This was identified as the target structure.

[0034] Example 2

[0035] The distillation column used θ-ring packing with 15 theoretical plates. 910.8 g (5 mol) of cyclododecanone, 858.7 g (5.5 mol) of acetone-diallyl alcohol, 1.82 g of p-toluenesulfonic acid, and 0.45 g of rhodium acetate were added to the bottom of the distillation column. The operation was carried out under an inert gas atmosphere, with a bottom operating temperature of 150℃ and a reflux ratio of 3:1. The top product of the distillation column was acetone. After 10 hours of reaction, gas chromatography analysis of the bottom liquid showed a cyclododecanone conversion of 98.3%, a cyclododecanone-diallyl alcohol selectivity of 80.2%, and a 2-(3-hydroxypropyl)cyclododecanone selectivity of 12.1%.

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

[0037] Example 3

[0038] The distillation column used θ-ring packing with 20 theoretical plates. 910.8 g (5 mol) of cyclododecanone, 1014.8 g (6.5 mol) of acetone-diallyl alcohol, 4.54 g of p-toluenesulfonic acid, and 0.91 g of rhodium acetate were added to the bottom of the distillation column. The operation was carried out under an inert gas atmosphere, with a bottom operating temperature of 100℃ and a reflux ratio of 10:1. The top product from the distillation column was acetone. After 16 hours of reaction, gas chromatography analysis of the bottom liquid showed a cyclododecanone conversion of 98.5%, a cyclododecanone-diallyl alcohol selectivity of 84.6%, and a 2-(3-hydroxypropyl)cyclododecanone selectivity of 8.9%.

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

[0040] Example 4

[0041] The distillation column used θ-ring packing with 10 theoretical plates. 910.8 g (5 mol) of cyclododecanone, 1561.2 g (10 mol) of acetone-diallyl alcohol, 9.11 g of p-toluenesulfonic acid, and 0.18 g of tetrarhodium dodecylcarbonyl were added to the bottom of the distillation column. The operation was conducted under an inert gas atmosphere, with a bottom operating temperature of 170℃ and a reflux ratio of 5:1. The top product from the distillation column was acetone. After 6 hours of reaction, gas chromatography analysis of the bottom liquid showed a cyclododecanone conversion of 99.6%, a cyclododecanone-diallyl alcohol selectivity of 75.7%, and a 2-(3-hydroxypropyl)cyclododecanone selectivity of 13.4%.

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

[0043] Comparative Example 1

[0044] Cyclododecanoic acid dielyl alcohol and 2-(3-hydroxypropyl)cyclododecanoic acid were prepared using the same method as in Example 1, the only difference being that no rhodium carbonyl acetylacetone was added to the reaction.

[0045] Tests showed that the bottom liquid of the condensation tower had a cyclododecanone conversion rate of 99.2%, a cyclododecanone diallyl alcohol selectivity of 65.7%, and a 2-(3-hydroxypropyl)cyclododecanone selectivity of 5.4%.

[0046] Tests showed that the conversion rate of cyclododecanone diallyl alcohol in the bottom liquid of the pyrolysis tower 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) Cyclododecone was used as a starting material to synthesize cyclododecone diallyl alcohol from acetone diallyl alcohol. (2) Dodecyl dienepropanol was further cleaved to give 2-(3-hydroxypropyl)cyclododecanone; Steps (1) and (2) are carried out in the presence of a rhodium metal compound.

2. The method according to claim 1, wherein, In step (1), the catalyst used is selected from acidic catalysts, and the amount of catalyst used is 0.1-2% of the mass of cyclododecanone.

3. The method according to claim 2, wherein, In step (1), the catalyst is selected from sulfonic acid compounds.

4. The method according to claim 3, wherein, In step (1), the catalyst is selected from one or more of methanesulfonic acid, ethylsulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid.

5. The method according to claim 2, wherein, In step (1), the amount of catalyst used is 0.2-0.5% of the mass of cyclododecanone.

6. The method according to claim 1, wherein, In step (1), the rhodium metal compound is selected from one or more of the following: inorganic acid salts of rhodium, carboxylates of rhodium, acetyl compounds of rhodium, and carbonyl compounds of rhodium; The amount of the rhodium metal compound used is 0.01-0.2% of the mass of cyclododecanone.

7. The method according to claim 6, wherein, In step (1), the rhodium metal compound is selected from one or more of rhodium acetate, rhodium nitrate, rhodium sulfate, rhodium bromide, rhodium acetylacetone carbonyl, tetrarhodium dodecyl, and hexadecyl hexarhodium. The amount of the rhodium metal compound used is 0.02-0.05% of the mass of cyclododecanone.

8. The method according to claim 1, wherein, In step (1), the molar ratio of cyclododecanone to acetone dienepropanol is 1:1 to 1:

5.

9. The method according to claim 8, wherein, In step (1), the molar ratio of cyclododecanone to acetone dienepropanol is 1:1.1-1:1.

5.

10. The method according to any one of claims 1-9, wherein, In step (1), the reaction temperature is 90-180℃.

11. The method according to claim 10, wherein, In step (1), the reaction temperature is 100-150℃.

12. The method according to any one of claims 1-9, wherein, In step (1), reactive distillation or reactive rectification is used; wherein the number of plates in the reactive distillation column is 5-30, and the reflux ratio in the reactive distillation column is 1-50:

1.

13. The method according to claim 12, wherein, In step (1), the number of plates in the reactive distillation column is 10-20, and the reflux ratio of the reactive distillation column is 3-10:

1.

14. The method according to claim 1, wherein, In step (2), the catalyst for the cracking reaction is selected from acidic catalysts; the amount of catalyst used is 0.1-2% of the mass of cyclododecanone.

15. The method according to claim 14, wherein, In step (2), the catalyst is selected from one or more of methanesulfonic acid, ethylsulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid; the amount of catalyst used is 0.2-0.5% of the mass of cyclododecanone.

16. The method according to claim 1, wherein, In step (2), the rhodium metal compound is selected from one or more of the following: inorganic acid salts of rhodium, carboxylates of rhodium, acetyl compounds of rhodium, and carbonyl compounds of rhodium; The amount of the rhodium metal compound used is 0.01-0.2% of the mass of cyclododecanone.

17. The method according to claim 1, wherein, In step (2), the rhodium metal compound is selected from one or more of rhodium acetate, rhodium nitrate, rhodium sulfate, rhodium bromide, rhodium acetylacetone carbonyl, tetrarhodium dodecyl, and hexadecyl hexarhodium. The amount of the rhodium metal compound used is 0.02-0.05% of the mass of cyclododecanone.

18. The method according to any one of claims 1, 14-17, wherein, In step (2), the pyrolysis reaction is carried out at 110-200℃.

19. The method according to claim 18, wherein, In step (2), the pyrolysis reaction is carried out at 120-160℃.

20. The method according to any one of claims 1, 14-17, wherein, In step (2), reactive distillation or reactive rectification is used; wherein the number of plates in the reactive distillation column is 5-30, and the reflux ratio in the reactive distillation column is 1-50:

1.

21. The method according to claim 20, wherein, In step (2), the number of plates in the reactive distillation column is 10-20, and the reflux ratio of the reactive distillation column is 3-10:1.

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