Novel preparation method of cis-6-nonenal
Through the reaction of cobium alcohol and triglyceride, combined with bromide, gog's coupling and hydrolysis steps, a high-earnings, high-purity cashier-6-relyne is successfully prepared to solve the complex preparation process in the existing technology. The problem of low purity has the potential of industrial applications.
Patent Information
- Application Number
- CN202411366842.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-09-29
- Publication Date
- 2025-01-21
AI Technical Summary
In the prior art, the preparation yield of cis-6-nonenal is low, the method is complicated, and isomers are prone to appear, resulting in low purity.
The use of lobolitanol and triglycemia as raw materials, through a series of reactions, including bromide, gog's coupling and hydrolysis, successfully prepared a smooth -6-deedin ascenal. This method includes a bromide reaction in the solvent mixing, generating 1-bromine-3-hexiene intermediate, and then generating a smooth-6-ethylene aldehyde intermediate through the grid reaction, and eventually hydrolyzed under acidic conditions Get the finished product of -6-elene aldehyde.
The income of the smooth -6-aldoin is increased, the generation of the heterogeneity is avoided, the purity of the product is significantly improved, and the response conditions and process routes are simplified, and it has potential industrial application prospects.
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Figure CN119330816A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to the technical field of preparation of flavors and fragrances, and in particular to a novel preparation method of cis-6-nonenal. Background Art
[0002] Green notes are one of the most important challenges that perfumers need to deal with in most food flavors. It is usually not the main note and only provides a fresh feeling without too many unique characteristics. Cis-6-nonenal has a fresh green fragrance, with obvious aroma elements of melon and cucumber, and a light vegetable aroma. The most obvious use of this raw material is in melon food flavors, but it can also bring useful fresh notes to many other categories of food flavors. However, the preparation of cis-6-nonenal in the prior art has the following technical defects: low yield and complicated preparation method, and isomers are easily produced during the preparation process, resulting in low purity. Summary of the invention
[0003] In order to solve the prior art problems raised in the above background technology, the present invention provides a novel preparation method of cis-6-nonenal. The present invention uses leaf alcohol as a raw material and replaces it with phosphorus tribromide bromine to obtain 1-bromo-3-hexene, and uses 1-bromo-3-hexene as a halogenated hydrocarbon to synthesize a Grignard reagent and 2-(2-bromoethyl)-1,3-dioxolane to carry out a Grignard coupling reaction to generate a cis-6-nonenal diethyl acetal intermediate, which is hydrolyzed to obtain a product cis-6-nonenal. The synthesis yield of the present invention is high, the product has no isomers, the purity is high, the reaction conditions are simple, the process route is simple, and it has potential industrial application prospects.
[0004] The purpose of the present invention can be achieved through the following technical solutions:
[0005] A novel preparation method of cis-6-nonenal comprises the following steps:
[0006] a. Leaf alcohol and phosphorus tribromide are used as raw materials and react in a mixed solvent of solvent A and solvent B to generate 1-bromo-3-hexene intermediate.
[0007] b.1-Bromo-3-hexene and magnesium chips undergo Grignard reaction in THF to generate hexenyl magnesium bromide Grignard reagent, add catalyst a and catalyst b to the mixed solution of solvent C and solvent D, heat to 85°C to flash out the solvent in the system, cool down, add solvent tetrahydrofuran, cool down the low temperature tank to a certain temperature, add 2-(2-bromoethyl)-1,3-dioxolane, maintain a certain temperature and drop the synthesized Grignard reagent, maintain the temperature after the dropwise addition, stir and react for a certain time. Add dilute hydrochloric acid to quench the reaction, separate the water and take the organic phase, and obtain the crude cis-6-nonenal diethyl acetal after alkali washing and flash evaporation.
[0008] c. The cis-6-nonenal diethyl acetal is hydrolyzed under acidic conditions to obtain the finished cis-6-nonenal.
[0009] Furthermore, the solvent A used in step a is one of petroleum ether, N-methylpyrrolidone and toluene, preferably N-methylpyrrolidone; the solvent B is one of petroleum ether, N-methylpyrrolidone and toluene, preferably petroleum ether;
[0010] Furthermore, in step a, the molar ratio of the reactants is leaf alcohol:phosphorus tribromide=1:0.5-1, preferably 1:0.6.
[0011] Furthermore, in step a, the reaction temperature is 0-20° C. and the reaction time is 2-10 h.
[0012] Furthermore, the solvent C and the solvent D in step b are two of petroleum ether, N-methylpyrrolidone, toluene and tetrahydrofuran, preferably N-methylpyrrolidone and toluene.
[0013] Furthermore, the molar ratio of the reactants in step b is 1-bromo-3-hexene: magnesium: catalyst b: catalyst a = 1: 1-1.2: 0.05-0.15: 0.05-0.15, preferably 1: 1.05: 0.06: 0.06.
[0014] Furthermore, in step b, the reaction temperature is -5-10°C and the reaction time is 2-10h.
[0015] Furthermore, the hydrolysis under acidic conditions in step c is hydrolysis in a 5% dilute sulfuric acid solution.
[0016] Furthermore, the mass ratio of the reactants in step c is cis-6-nonenal diethyl acetal: 5% dilute sulfuric acid = 1:5-15, preferably 1:10.
[0017] Furthermore, the reaction temperature of the hydrolysis in step c is 60-100° C., and the reaction time is 5-15 h.
[0018] The principle of the synthetic method of cis-6-nonenal is as follows:
[0019] 1. Leaf alcohol bromination (step a):
[0020]
[0021] 2. Grignard coupling (step b):
[0022]
[0023] 3. Hydrolysis (step c):
[0024]
[0025] Beneficial effects of the present invention:
[0026] The raw materials for the synthesis are low in price, the yield is high, the product has no isomers and has high purity, the reaction conditions are simple, the process route is simple, and it has potential industrial application prospects. BRIEF DESCRIPTION OF THE DRAWINGS
[0027] The present invention will be further described below in conjunction with the accompanying drawings.
[0028] Figure 1 This is the GC spectrum of the process of hydrolysis of cis-6-nonenal diethyl acetal to generate cis-6-nonenal.
[0029] Figure 2 This is the GC spectrum of the product cis-6-nonenal. DETAILED DESCRIPTION
[0030] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.
[0031] Example 1: Preparation of 1-bromo-3-hexene
[0032] Mix 215.5g of phosphorus tribromide and 800g of petroleum ether and add them to a 2L three-necked flask. Control the temperature at about 15-30°C and add 220g of leaf alcohol and 65.0g of NMP dropwise for about 2h. Continue stirring for about 6h after the addition is complete. Add the system to ice water to quench the temperature and keep it below 10°C. Take the oil phase by stratification. Then wash the oil phase with 5% sodium bicarbonate solution to make it neutral.
[0033] The system was heated to 65°C and the solvent petroleum ether was recovered. The kettle temperature was 60°C and the pressure was slightly negative at 0.85 MPa. The front fraction was collected and the content was <90%. The 30 cm thorn column was heated to 63°C under full negative pressure and the product was collected and the content was >98%. The crude 1-bromo-3-hexene was obtained with a yield of 78%.
[0034] Example 2: Preparation of 1-bromo-3-hexene
[0035] Mix 215.5g of phosphorus tribromide and 800g of petroleum ether and add them to a 2L three-necked flask. Control the temperature at about 0-10°C and add 220g of leaf alcohol and 65.0g of NMP dropwise for about 2h. Continue stirring for about 6h after the addition is complete. Add the system to ice water to quench the temperature and keep it below 10°C. Take the oil phase by stratification. Then wash the oil phase with 5% sodium bicarbonate solution to make it neutral.
[0036] The system was heated to 65°C and the solvent petroleum ether was recovered. The kettle temperature was 60°C and the pressure was slightly negative at 0.85 MPa. The front fraction was collected and the content was <90%. The 30 cm thorn column was heated to 63°C under full negative pressure and the product was collected and the content was >98%. The crude 1-bromo-3-hexene was obtained with a yield of 80%.
[0037] Example 3: Preparation of 1-bromo-3-hexene
[0038] Mix 150g of phosphorus tribromide and 400g of petroleum ether and add them to a 2L three-necked flask. Control the temperature at about 0-10°C and add 220g of leaf alcohol and 65.0g of NMP dropwise for about 2h. After the addition is complete, add the remaining 65g of phosphorus tribromide and 400g of petroleum ether mixture dropwise. Continue stirring for about 6h after the addition is complete. Add the system to ice water to quench the temperature and keep it below 10°C. Take the oil phase by stratification. Then wash the oil phase with 5% sodium bicarbonate solution to make it neutral.
[0039] The system was heated to 65°C and the solvent petroleum ether was recovered. The kettle temperature was 60°C and the pressure was slightly negative at 0.85 MPa. The front fraction was collected and the content was <90%. The 30 cm thorn column was heated to 63°C under full negative pressure and the product was collected and the content was >98%. The crude 1-bromo-3-hexene was obtained with a yield of 85%.
[0040] Embodiment 4: the preparation of cis-6-nonenal diethyl acetal
[0041] Synthesize Grignard reagent: 500ml three-port nitrogen is passed to remove air, add 8.0g magnesium chips and 75g THF, add 5g 1-bromo-3-hexene dropwise, after the reaction is initiated, control the kettle temperature at 55℃ and add 35.0g 1-bromo-3-hexene and 175g THF dropwise. Add dropwise for 2h. Obtain Grignard reagent for use.
[0042] Synthesis of lithium copper tetrachloride and dehydration: Add 0.75g of catalyst a and 2.25g of catalyst b into a 100ml three-necked flask, add 95g of toluene and 95g of NMP. Flash out toluene and water in the system. Cool down after flashing out.
[0043] Synthesis of cis-6-nonenal diethyl acetal: Cool the dehydrated system to -10-0°C, add 250g THF, and add 42.0g 2-(2-bromoethyl)-1,3-dioxolane. Start dripping the Grignard reagent at -10-0°C, and continue the reaction with stirring for 3h.
[0044] Post-treatment: quench first, add 150g 8% HCl solution to the system, and control the system temperature to 0-10°C. After quenching, separate the oil phase and wash the solution to neutral. Separate the oil phase. Raise the temperature and negative pressure to recover the system solvent THF. Raise the negative pressure of the oil pump to 75°C to obtain the crude product of cis-6-nonenal diethyl acetal. The crude product content is 97.2%, and the yield is 66%.
[0045] Embodiment 5: the preparation of cis-6-nonenal diethyl acetal
[0046] Synthesize Grignard reagent: 500ml three-port nitrogen is passed to remove air, add 8.0g magnesium chips and 75g THF, add 5g 1-bromo-3-hexene dropwise, after the reaction is initiated, control the kettle temperature at 55℃ and add 35.0g 1-bromo-3-hexene and 175g THF dropwise. Add dropwise for 2h. Obtain Grignard reagent for use.
[0047] Synthesis of lithium copper tetrachloride and dehydration: Add 0.75g of catalyst a and 2.25g of catalyst b into a 100ml three-necked flask, add 95g of toluene and 95g of NMP. Flash out toluene and water in the system. Cool down after flashing out.
[0048] Synthesis of cis-6-nonenal diethyl acetal: Cool the dehydrated system to -10-0°C, add 250g THF, and add 50.0g 2-(2-bromoethyl)-1,3-dioxolane. Start dripping the Grignard reagent at -10-0°C, and continue the reaction with stirring for 3h.
[0049] Post-treatment: quench first, add 150g 8% HCl solution to the system, and control the system temperature to 0-10°C. After quenching, separate the oil phase and wash the solution to neutral. Separate the oil phase. Raise the temperature and negative pressure to recover the system solvent THF. Raise the negative pressure of the oil pump to 75°C to obtain the crude product of cis-6-nonenal diethyl acetal. The crude product content is 97.2%, and the yield is 70%.
[0050] Embodiment 6: preparation of cis-6-nonenal
[0051] Prepare 170g of 5% dilute sulfuric acid, add it into 250ml of three-well, add 170g of cis-6-nonenal diethyl acetal, stir and hydrolyze at about 20℃. After stirring, separate the layers to obtain the oil phase, and flash evaporate the oil phase to obtain cis-6-nonenal with a content of 97.8% and a yield of 44%. Figure 1 The GC spectrum of the process of hydrolysis of cis-6-nonenal diethyl acetal to cis-6-nonenal is shown. Figure 2 Shown is the GC spectrum of the obtained product cis-6-nonenal.
[0052] Example 7: Preparation of cis-6-nonenal
[0053] Prepare 170g of 10% dilute sulfuric acid, add it into 250ml three-well, add 170g of cis-6-nonenal diethyl acetal, stir and hydrolyze at about 20°C. After stirring, separate the layers to obtain an oil phase, and flash evaporate the oil phase to obtain cis-6-nonenal with a content of 96.6% and a yield of 53.8%.
[0054] Embodiment 8: Preparation of cis-6-nonenal
[0055] Prepare 170g of 10% dilute sulfuric acid, add it into 250ml three-well, add 170g of cis-6-nonenal diethyl acetal, stir and hydrolyze at about 50°C. After stirring, separate the layers to obtain an oil phase, and flash evaporate the oil phase to obtain cis-6-nonenal with a content of 98.6% and a yield of 56.8%.
[0056] The above specific implementation method part specifically introduces the analytical method involved in the present invention. It should be noted that the above introduction is only to help those skilled in the art better understand the method and ideas of the present invention, rather than limiting the relevant content. Without departing from the principle of the present invention, those skilled in the art may also make appropriate adjustments or modifications to the present invention, and the above adjustments and modifications shall also fall within the scope of protection of the present invention.
Claims
1. A novel method for preparing cis-6-nonenal, characterized in that: The following steps are involved: a. Leaf alcohol and phosphorus tribromide as raw materials react in a mixed solvent of solvent A and solvent B to generate 1-bromo-3-hexene intermediate; b. 1-Bromo-3-hexene and magnesium chips undergo Grignard reaction in THF to generate hexenyl magnesium bromide Grignard reagent, catalyst a and catalyst b are added to a mixed solution of solvent C and solvent D, the temperature is raised to 85°C to flash out the solvent in the system, the temperature is lowered, tetrahydrofuran solvent is added, the temperature in the low temperature tank is lowered to a certain temperature, 2-(2-bromoethyl)-1,3-dioxolane is added, the synthesized Grignard reagent is added dropwise while maintaining a certain temperature, and after the addition is completed, the temperature is maintained and stirred for a certain period of time, and post-processed to obtain a crude product of cis-6-nonenal diethyl acetal; c. The cis-6-nonenal diethyl acetal is hydrolyzed under acidic conditions to obtain the finished cis-6-nonenal.
2. A novel method for preparing cis-6-nonenal according to claim 1, characterized in that: The solvent A used in step a is one of petroleum ether, N-methylpyrrolidone and toluene; the solvent B is one of petroleum ether, N-methylpyrrolidone and toluene.
3. A novel method for preparing cis-6-nonenal according to claim 1, characterized in that: The molar ratio of the reactants in step a is leaf alcohol:phosphorus tribromide=1:0.5-1.
4. A novel method for preparing cis-6-nonenal according to claim 1, characterized in that: In step a, the reaction temperature is 0-20° C. and the reaction time is 2-10 h.
5. A novel method for preparing cis-6-nonenal according to claim 1, characterized in that: In step b, the solvent C and the solvent D are two of petroleum ether, N-methylpyrrolidone, toluene and tetrahydrofuran.
6. A novel method for preparing cis-6-nonenal according to claim 1, characterized in that: The molar ratio of the reactants in step b is 1-bromo-3-hexene: magnesium: catalyst b: catalyst a=1:1-1.2:0.05-0.15:0.05-0.
15.
7. A novel method for preparing cis-6-nonenal according to claim 1, characterized in that: In step b, the reaction temperature is -5-10°C and the reaction time is 2-10h.
8. A novel method for preparing cis-6-nonenal according to claim 1, characterized in that: In step c, the hydrolysis under acidic conditions is hydrolysis in a 5% dilute sulfuric acid solution.
9. A novel method for preparing cis-6-nonenal according to claim 8, characterized in that: The mass ratio of the reactants in step c is cis-6-nonenal diethyl acetal: 5% dilute sulfuric acid = 1:5-15.
10. A novel method for preparing cis-6-nonenal according to claim 1, characterized in that: The reaction temperature of the hydrolysis in step c is 60-100° C., and the reaction time is 5-15 h.