Preparation method of trimethyl cyclododecatriene
By catalyzing the trimerization of isoprene under the synergistic effect of catalyst and Lewis acid, the problems of poor selectivity and cumbersome steps in the existing technology are solved, and the highly selective synthesis of all-E-form 1,5,9-trimethyl-1,5,9-cyclododecanetriene is achieved, simplifying the process.
Patent Information
- Application Number
- CN202510927052.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-07-07
- Publication Date
- 2025-11-07
AI Technical Summary
In existing synthetic processes, the trimerization of isoprene to form all-E 1,5,9-trimethyl-1,5,9-cyclododecanetriene has poor selectivity, the steps are cumbersome and require expensive methyl Grignard reagents, and separation is difficult.
Under the synergistic effect of catalyst and Lewis acid, isoprene trimerization is catalyzed by a complex of metal Pd monomer and dinitrogen ligand to generate all-trans 1,5,9-trimethyl-1,5,9-cyclododecanetriene. The reaction conditions include specific temperature and solvent system.
It improves the selectivity of isoprene trimerization to the all-E product, simplifies the synthesis steps, avoids the use of expensive reagents, and reduces the difficulty of separation.
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Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the field of organic synthesis, and in particular to a preparation method of 1,5,9-trimethyl-1,5,9-cyclododecatriene. BACKGROUND
[0002] Isoprene can be synthesized by petroleum method, mainly by separating isoprene from cracked gasoline to produce isoprene. Isoprene trimerization usually generates mixed cyclic or linear products (such as six-membered ring or linear oligomers), and there are at least 8 isomers for a twelve-membered ring skeleton structure, and it is very challenging to synthesize a full E type (all trans) twelve-membered ring carbon triene structure with high selectivity. In the previously reported synthesis methods, the double bond configuration control in the isoprene polymerization reaction is poor, and the product is mostly a Z / E (normal / trans) mixture.
[0003] Full E type 1,5,9-trimethyl-1,5,9-cyclododecatriene (chemical formula C 15 H 24 ) is a key raw material for synthesizing suvoral. Suvoral is a colorless to pale yellow liquid with a woody, amber, musk, cedar and tobacco odor. Suvoral is mainly used in the perfume industry and is widely used in perfumes, cosmetics and personal care products to provide unique woody and amber aroma.
[0004] The existing synthesis process uses cyclododecatriene as a starting material, then introduces three methyl groups in the skeleton structure through methylation modification, mainly by reacting methyl Grignard reagent and other methyl donors with a cyclic intermediate to synthesize trimethyl cyclododecatriene, and then separating 1,5,9-trimethyl-1,5,9-cyclododecatriene, and finally performing acetylation reaction to synthesize suvoral. The existing synthesis route is complicated, requires expensive methyl Grignard reagent, has poor selectivity, and is difficult to separate. Therefore, high-selectivity synthesis of full E type twelve-membered ring carbon triene skeleton has strong potential commercial value. SUMMARY
[0005] The purpose of the present application is to overcome the deficiencies in the prior art and provide a preparation method for high-selectivity trimerization of isoprene to synthesize full E type 1,5,9-trimethyl-1,5,9-cyclododecatriene.
[0006] To achieve the above-mentioned purpose of the application, the technical solutions of the present application are as follows:
[0007] In a first aspect, a preparation method of 1,5,9-trimethyl-1,5,9-cyclododecatriene is provided, in which the isoprene is trimerized to generate full trans 1,5,9-trimethyl-1,5,9-cyclododecatriene with high selectivity under the synergistic action of a catalyst and a Lewis acid, and the reaction route is shown in the following formula:
[0008]
[0009] In the present application, the catalyst comprises a metal Pd monomer and a double nitrogen ligand. The metal Pd monomer comprises one or more of palladium acetate, allyl palladium chloride, palladium acetylacetonate (Pd(acac)2), palladium bromide (PdBr2), palladium chloride (PdCl2), palladium iodide (PdI2), and tetrakis(triphenylphosphine)palladium, and the amount of the metal Pd monomer is 0.01-0.2 mol% of isoprene.
[0010] In the present application, the double nitrogen ligand comprises one or more of the substances shown in the following formulae L1-L5, and the amount of the double nitrogen ligand is 0.8-1.3 eq. of the molar amount of the metal Pd monomer, preferably 1.0-1.1 eq.
[0011]
[0012] In the formulae L1-L5, Me is methyl, t Bu is tert-butyl.
[0013] In the present application, the Lewis acid comprises one or more of zinc oxide, zinc acetate, zinc stearate, zinc chloride, lithium chloride, lithium bromide, magnesium chloride, magnesium bromide, niobium pentachloride, scandium trifluoromethyl sulfonate, yttrium trifluoromethyl sulfonate, and boron trifluoride; preferably, the Lewis acid is selected from one or more of zinc acetate, zinc stearate, zinc chloride, lithium chloride, magnesium bromide, niobium pentachloride, and scandium trifluoromethyl sulfonate, and the amount of the Lewis acid is 0.01-0.5 wt.% of the mass of isoprene, preferably 0.05-0.25 wt.%.
[0014] In the present application, the temperature of the above-mentioned polymerization reaction is 60-150°C, preferably 90-120°C, the reaction time is 2-5 h, and the reaction pressure is normal pressure.
[0015] In the present application, the above-mentioned polymerization reaction is carried out in a solvent, and the solvent used comprises one or more of hexane, pentane, heptane, octane, cyclohexane, toluene, xylene, trichloromethane (chloroform), 1,2-dichloroethane, methanol, ethanol, isopropanol, n-butanol, ethylene glycol, acetone, methyl ethyl ketone, cyclohexanone, ethyl acetate, butyl acetate, diethyl ether, and tetrahydrofuran, and the amount of the solvent is 0.1-3 times the mass of isoprene.
[0016] In the present application, the catalyst is a complex of a metal Pd monomer and a double nitrogen ligand, and specifically, in the preparation of 1,5,9-trimethyl-1,5,9-cyclododecatriene, the metal Pd monomer and the double nitrogen ligand are first subjected to a one-step complexation reaction, and then isoprene and a Lewis acid are added to carry out a polymerization reaction, thereby obtaining 1,5,9-trimethyl-1,5,9-cyclododecatriene.
[0017] Specifically, the complexation reaction is at room temperature, and the complexation reaction process is preferably accompanied by stirring, and the reaction duration is 5-40 min. Then, isoprene and Lewis acid are added to prepare 1,5,9-trimethyl-1,5,9-cyclododecatriene.
[0018] In a second aspect, the present application provides the use of the above-mentioned full E 1,5,9-trimethyl-1,5,9-cyclododecatriene, which is mainly used as a pharmaceutical intermediate or a fragrance intermediate.
[0019] Compared with the prior art, the present application has the beneficial effects of shortening the synthesis steps of trimethyl dodecatriene, avoiding the use of expensive reagents such as methyl Grignard reagent, simplifying the post-processing, and improving the selectivity of the reaction. DETAILED DESCRIPTION
[0020] In order to further illustrate the present application, several specific implementation examples are given below, but the present application is not limited to these examples.
[0021] Detection method and instrument:
[0022] (1) GC detection: Agilent 8890, chromatographic column: HP-INNOWAX (stationary phase polyethylene glycol, specification 30 m x 0.25 mm x 0.25 μm);
[0023] Temperature rising program: initial temperature 50℃, rising to 80℃ at 5℃ / min, holding for 2min, then rising to 240℃ at 15℃ / min, holding for 15min; injection port temperature: 230℃; FID detector temperature: 250℃; split injection, split ratio 30:1; injection volume: 1.0 μL; carrier gas flow rate (nitrogen): 1 mL / min; hydrogen flow rate: 30 mL / min; air flow rate: 400 mL / min; tail gas flow rate: 25 mL / min.
[0024] (2) NMR analysis: Bruker 400MHz liquid nuclear magnetic resonance instrument, test temperature is 25℃.
[0025] Example 1
[0026] In a glove box, palladium acetate (0.22 g) and ligand L1 (0.17 g) were added to 1 L reactor with toluene (60 g) at room temperature (25 °C) and stirred for 15 min. Isoprene (68 g) and zinc acetate (0.34 g) were added to the reactor, and the stirring was started. The temperature was raised to 120 °C, and the reaction was continued for 3 h. The reaction was stopped, and the solvent was removed to obtain the crude product. The selectivity of the reaction was 89.1%. The full E 1,5,9-trimethyl-1,5,9-cyclododecatriene (61.20 g) was obtained by column chromatography with a purity of 99.0%.
[0027] The full E 1,5,9-trimethyl-1,5,9-cyclododecatriene has the following structure:
[0028]
[0029] The full E 1,5,9-trimethyl-1,5,9-cyclododecatriene has the following structure:
[0030] 1 HNMR (400 MHz, CDC13): δ 5.20 (t, J = 6.8 Hz, 3H), 2.05 (q, J = 6.8 Hz, 12H), 1.78 (s, 9H). 13 CNMR (100 MHz, CDC13): δ 135.3, 129.5, 42.0, 25.1, 16.4.
[0031] Example 2
[0032] In a glove box, palladium acetate (0.22 g) and ligand L1 (0.17 g) were added to 1 L reactor with toluene (60 g) at room temperature (25 °C) and stirred for 15 min. Isoprene (68 g) and zinc acetate (0.34 g) were added to the reactor, and the stirring was started. The temperature was raised to 120 °C, and the reaction was continued for 3 h. The reaction was stopped, and the solvent was removed to obtain the crude product. The selectivity of the reaction was 89.1%. The full E 1,5,9-trimethyl-1,5,9-cyclododecatriene (61.20 g) was obtained by column chromatography with a purity of 99.0%.
[0033] Example 3
[0034] In a glove box, allyl palladium (0.18 g) and ligand L5 (0.27 g) were added to cyclohexane (150 g) in a 1 L reaction kettle, and the complex was stirred at room temperature (25 °C) for 30 min. Isoprene (68 g) and boron trifluoride (0.17 g) were then added to the reaction kettle, and the reaction was stirred and heated to 110 °C for 3 h. The reaction was then stopped. The reaction was sampled through the bottom of the kettle, and the reaction was analyzed by GC. The conversion of isoprene was 98%. The solvent was then removed to give a crude product. The selectivity of the reaction was 84.14%. The full E 1,5,9-trimethyl-1,5,9-cyclododecatriene (56.64 g) was isolated by column chromatography, and the purity was 99.0%.
Claims
1. A process for the preparation of 1,5,9-trimethyl-1,5,9-cyclododecatriene, characterized in that: Under the synergistic effect of the catalyst and the Lewis acid, isoprene is polymerized to generate 1,5,9-trimethyl-1,5,9-cyclododecatriene.
2. The method of claim 1, wherein: The catalyst is a complex of a metal Pd monomer and a double nitrogen ligand, the metal Pd monomer includes one or more of palladium acetate, allyl palladium chloride, palladium acetylacetone, palladium bromide, palladium chloride, palladium iodide, and tetrakis(triphenylphosphine)palladium, and the amount of the metal Pd monomer is 0.01-0.2 mol% of the molar amount of isoprene.
3. The method of claim 2, wherein: The double nitrogen ligand includes one or more of the substances shown in the structures of formulae L1-L5, and the amount is preferably 0.8-1.3 eq of the molar amount of the metal Pd monomer, and more preferably 1.0-1.1 eq.
4. The method of claim 3, wherein: The metal Pd monomer and the double nitrogen ligand are first subjected to a complexation reaction, and then isoprene and the Lewis acid are added for polymerization; preferably, the complexation reaction time is 5-40 min.
5. The method of claim 1, wherein: The Lewis acid includes one or more of zinc oxide, zinc acetate, zinc stearate, zinc chloride, lithium chloride, lithium bromide, magnesium chloride, magnesium bromide, niobium pentachloride, scandium trifluoromethyl sulfonate, yttrium trifluoromethyl sulfonate, and boron trifluoride; preferably, the amount of the Lewis acid is 0.01-0.5 wt% of the mass of isoprene, and preferably 0.05-0.25 wt%.
6. The production method according to any one of claims 1 to 5, characterized by: The temperature of the isoprene polymerization reaction is 60-150°C, and preferably 90-120°C, and the reaction time is 2-5 h.
7. The method of claim 6, wherein: The polymerization reaction is carried out in a solution, and the solvent used includes one or more of hexane, pentane, heptane, octane, cyclohexane, toluene, xylene, chloroform, 1,2-dichloroethane, methanol, ethanol, isopropanol, n-butanol, ethylene glycol, acetone, methyl ethyl ketone, cyclohexanone, ethyl acetate, butyl acetate, diethyl ether, and tetrahydrofuran, and the amount of the solvent is preferably 0.1-3 times the mass of isoprene.
8. The use of 1,5,9-trimethyl-1,5,9-cyclododecatriene synthesized by the preparation method of any one of claims 1-7 in the field of pharmaceutical intermediates or perfume intermediates.