Method for synthesizing neroli through 4-methyl-4-[(3-methylbutyl-3-en-1-yl) oxy]-2-(2-methylpropyl-1-en-1-yl) oxane
By using SO42--Fe2O3-La2O3/SBA-15 solid acid catalyst, the problem of the byproduct being difficult to convert into nerol was solved, realizing efficient and environmentally friendly nerol production and reducing the equipment requirements and wastewater discharge for industrial production.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- 江苏宏邦化工科技有限公司
- Filing Date
- 2025-12-18
- Publication Date
- 2026-05-12
AI Technical Summary
In existing technologies, the byproduct 4-methyl-4-[(3-methylbut-3-en-1-yl)oxy]-2-(2-methylprop-1-en-1-yl)oxacyclohexane is difficult to convert into useful neroli ether products efficiently, and traditional liquid acid catalysts have high equipment requirements and generate a large amount of wastewater, resulting in high industrial production costs.
By using SO42--Fe2O3-La2O3/SBA-15 solid acid catalyst and controlling the reaction temperature, pressure, flow rate and additives, the byproducts are efficiently converted into neroli ether. The use of solid acid catalyst avoids equipment corrosion and wastewater generation.
It achieves high conversion rate (greater than 99%) and high selectivity (greater than 85%) of by-products, reduces production costs, and is suitable for industrial production.
Smart Images
Figure CN122010886A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of organic synthesis technology and relates to the synthesis of the fragrance compound nerol, and particularly to a method for synthesizing nerol via 4-methyl-4-[(3-methylbut-3-en-1-yl)oxy]-2-(2-methylprop-1-en-1-yl)oxacyclohexane. Background Technology
[0002] 3,6-Dihydro-4-methyl-2-(2-methyl-1-propenyl)-2H-pyran, commonly known as neroli ether, possesses a strong floral aroma, reminiscent of neroli oil, and a fresh, youthful scent. It is frequently used in floral fragrances such as orange blossom, jasmine, honeysuckle, and hyacinth, and can also be used in fresh citrus / green notes, providing brightness in the top notes, a natural transition in the middle notes, and a harmonious base note with musk and woody notes. It is also used in citrus and tropical fruit flavors, and in low-sugar / sugar-free beverages and candies, it can significantly improve the flavor defects of artificial sweeteners and enhance palatability. Furthermore, its hydrogenated product, dihydrorose ether, has a strong floral aroma and is a relatively stable aroma-building material that can replace less stable floral fragrances. Therefore, the chemical synthesis of neroli ether has significant application value.
[0003] Currently, there are two main methods for synthesizing nerol. One method uses nerol / geraniol as raw materials and obtains the corresponding nerol through a three-step reaction involving bromination-alkane oxidation, elimination, and cyclization. The bromination reagents used in this method are relatively expensive, resulting in high production costs, and the overall yield of the three-step reaction is no higher than 70%, requiring large batch sizes. The second method uses isopentenal and isopentenol for direct Prins cyclization to obtain nerol in a single step. For example, patent CN116041299A describes a method for synthesizing nerol using a liquid strong acid as a catalyst and molecular sieves as an auxiliary agent, ultimately achieving a 90% yield of nerol. The catalyst used in the second method is cheaper than that in the first method, and the operation is simpler, making it easier for industrial production. The final yield of 90% is mainly due to the formation of approximately 10% of the byproduct 4-methyl-4-[(3-methylbut-3-en-1-yl)oxy]-2-(2-methylprop-1-en-1-yl)oxacyclohexane during the reaction. The reaction mechanism is as follows: isopentenal and isopentenol react to generate intermediate A. Intermediate A undergoes β-H elimination to yield nerol. However, the intermediate also reacts further with isopentenol to give the byproduct 4-methyl-4-[(3-methylbut-3-en-1-yl)oxy]-2-(2-methylprop-1-en-1-yl)oxacyclohexane, which constitutes approximately 10% of the product. Therefore, converting the byproduct into the useful nerol product is crucial for improving the reaction yield.
[0004]
[0005] Byproduct structural analysis revealed that the byproduct is an ether-based substrate. Traditionally, etherification is performed using liquid acids such as hydroiodic acid aqueous solution. However, these liquid acids are highly corrosive, requiring sophisticated equipment and generating large amounts of wastewater in the post-treatment process, resulting in high levels of waste from the reaction. In summary, using traditional hydroiodic acid-based liquid acids not only demands sophisticated equipment but also requires large amounts of alkaline water for neutralization, leading to high levels of waste and high industrialization costs. Furthermore, the yield is generally low, hindering industrial production. Therefore, the efficient synthesis of neroli ether from 4-methyl-4-[(3-methylbut-3-en-1-yl)oxy]-2-(2-methylprop-1-en-1-yl)oxacyclohexane would significantly promote the industrialization of neroli ether. Summary of the Invention
[0006] To address the shortcomings of existing technologies, the present invention aims to provide a method for synthesizing nerol from 4-methyl-4-[(3-methylbut-3-en-1-yl)oxy]-2-(2-methylprop-1-en-1-yl)oxacyclohexane. The present invention utilizes SO4. 2- Using Fe2O3-La2O3 / SBA-15 solid acid as a catalyst, and through screening of reaction temperature, reaction pressure, auxiliary agents, and reaction flow rate, a highly efficient synthesis of neroli ether was successfully achieved from the byproduct 4-methyl-4-[(3-methylbut-3-en-1-yl)oxy]-2-(2-methylprop-1-en-1-yl)oxacyclohexane was successfully achieved. The method has low equipment requirements, relatively mild reaction conditions, fast reaction rate, high production efficiency, and is easily scalable for industrial production.
[0007] This invention is achieved through the following technical solution: A method for synthesizing neroli ether from 4-methyl-4-[(3-methylbut-3-en-1-yl)oxy]-2-(2-methylprop-1-en-1-yl)oxacyclohexane includes the following steps: mixing the raw material 4-methyl-4-[(3-methylbut-3-en-1-yl)oxy]-2-(2-methylprop-1-en-1-yl)oxacyclohexane with a solvent until homogeneous, preheating the mixture using a preheater, and then feeding it into a container filled with SO4 at a certain flow rate. 2- The reaction was carried out in a fixed-bed reactor with Fe2O3-La2O3 / SBA-15 solid acid catalyst. The reaction was carried out at a certain temperature and pressure for a period of time. After the reaction, the crude product was obtained by cooling in a condenser. The crude product was then distilled to obtain nerol product and isopentenol byproduct. The SO4 2- In the Fe2O3-La2O3 / SBA-15 solid acid catalyst, the molar ratio of La to Fe is 1:8~10, the total loading of Fe2O3 and La2O3 is 1.5~4%, and the molar ratio of sulfate to ferric oxide on the surface of the solid acid catalyst is 1.5~1.8.
[0008] The reaction equation is shown below:
[0009] A further improvement to the present invention is as follows: The solvents used are toluene, cyclohexane, n-hexane, n-heptane, ethyl acetate, acetonitrile, tetrahydrofuran, ethylene glycol dimethyl ether, 1,4-dioxane, N,N-dimethylacetamide, N,N-diethylacetamide, N-methylpyrrolidone, N-ethylpyrrolidone, or water, or a mixture of two or more of these solvents.
[0010] Furthermore, the amount of solvent used is 0.2 to 3 times the mass of the raw material.
[0011] Furthermore, the preheating temperature is 60℃~120℃, the reaction temperature is 120℃~240℃, and the condenser temperature is 30℃~80℃.
[0012] Furthermore, the reaction pressure is 101 kPa to 550 kPa.
[0013] Furthermore, the feed flow rate is 10~80mL / min, and the residence time of the material in the reactor is 10s-200s.
[0014] Furthermore, the fixed-bed reactor has a diameter of 25 mm, the catalyst filling height is 400-800 mm, and the loading amount is 50-100 g.
[0015] Furthermore, the SO4 2- The Fe2O3-La2O3 / SBA-15 solid acid catalyst was prepared by the following steps: An equal volume of SBA-15 was impregnated in a mixed aqueous solution of lanthanum nitrate and ferric nitrate. After standing, the mixture was transferred to a hydrothermal reactor containing ethanol for hydrothermal reaction. Following the reaction, the mixture was dried and subjected to a first high-temperature treatment. The resulting powder was heated and stirred in an aqueous solution of (NH4)2SO4, then filtered, dried, and subjected to a second high-temperature treatment to obtain SO4. 2- -Fe2O3-La2O3 / SBA-15 solid acid catalyst.
[0016] Furthermore, the hydrothermal reaction is carried out at a temperature of 100-150°C for 3-5 hours.
[0017] Furthermore, the drying temperature is 100~120℃, and the time is 10~14h.
[0018] Furthermore, the first high-temperature treatment process is as follows: the temperature is increased to 500℃ in a muffle furnace at a rate of 2.5℃ / min and held for 5 hours.
[0019] Furthermore, the heating and stirring temperature is 70~90℃ and the stirring is carried out for 4~8 hours.
[0020] Furthermore, the second high-temperature treatment process is as follows: the temperature is increased to 550°C in a muffle furnace at a rate of 5°C / min and held for 4 hours.
[0021] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) The present invention has high conversion rate and good selectivity. At the end of the reaction, the conversion rate of the raw material 4-methyl-4-[(3-methylbut-3-en-1-yl)oxy]-2-(2-methylprop-1-en-1-yl)oxacyclohexane is greater than 99%, and the selectivity of the product neroli is greater than 85%. At the same time, the by-product isopentenol can be used to further synthesize neroli.
[0022] (2) The catalyst used in this invention is SO4. 2- The Fe2O3-La2O3 / SBA-15 solid acid catalyst eliminates the need for water washing after the reaction, thus preventing the generation of industrial wastewater and reducing environmental costs.
[0023] (3) The solid acid catalyst used in this method can be reused, up to 5 batches. The deactivated catalyst can be restored to activity by being impregnated with ammonium sulfate and then calcined again, which greatly reduces the production cost. Attached Figure Description
[0024] Figure 1 The 1H NMR spectrum of 4-methyl-4-[(3-methylbut-3-en-1-yl)oxy]-2-(2-methylprop-1-en-1-yl)oxacyclohexane, the raw material of this invention; Figure 2 The carbon NMR spectrum of the raw material 4-methyl-4-[(3-methylbut-3-en-1-yl)oxy]-2-(2-methylprop-1-en-1-yl)oxacyclohexane. Detailed Implementation
[0025] The present invention will now be described in detail with reference to specific embodiments.
[0026] The raw material used in this invention, 4-methyl-4-[(3-methylbut-3-en-1-yl)oxy]-2-(2-methylprop-1-en-1-yl)oxacyclohexane, is a byproduct generated during the one-step Prins cyclization process of isopentenal and isopentenol to prepare neroli ether, which is obtained by separation and purification.
[0027]
[0028] Example 1: SO4 2- Preparation of Fe2O3-La2O3 / SBA-15 solid acid catalyst 47 g of template agent P123 (PEO-PPO-PEO) was added to 1.4 L of 2 M dilute hydrochloric acid solution and stirred vigorously at 35 °C. Then, 100.0 g of tetraethyl orthosilicate was added dropwise and stirred for 16 h. After the reaction was completed, the mixture was placed in a high-pressure reactor with a polytetrafluoroethylene liner and crystallized at 100 °C for 24 h. The resulting solid-liquid mixture was filtered, washed several times with distilled water, dried at 110 °C with forced air for 12 h, and calcined in a tube furnace at 550 °C with an air flow (10 mL / min) for 5 h to remove the organic template agent.
[0029] Subsequently, 0.32 g of La(NO3)3•6H2O and 2.73 g of Fe(NO3)3•9H2O were weighed to prepare 15 mL of a mixed aqueous solution (this is the saturated adsorbed water volume of the above SBA-15). Approximately 28.5 g of the above product SBA-15 was impregnated with an equal volume of a mixed aqueous solution of lanthanum nitrate and ferric nitrate. After standing at room temperature for 12 h, the powder was placed in a glass bottle and then placed in a hydrothermal reactor. 5 g of ethanol was added to the bottom of the reactor, and the temperature was raised to 120 °C for hydrothermal treatment for 4 h. This step effectively ensures that the pores of SBA-15 remain more uniform. The impregnated catalyst precursor was dried at 110 °C with forced air for 12 h, heated to 500 °C in a muffle furnace at 2.5 °C / min and held for 5 h, then allowed to cool naturally to room temperature to obtain Fe2O3-La2O3 / SBA-15. Prepare 60 mL of (NH4)2SO4 aqueous solution (0.5 mol / L), add the above Fe2O3-La2O3 / SBA-15 powder to it, stir at 80℃ for 6 h, filter, dry, heat in a muffle furnace to 550℃ at 5℃ / min and hold for 4 h, then allow to cool naturally to room temperature to obtain SO4. 2- -Fe2O3-La2O3 / SBA-15 solid acid catalyst.
[0030] Example 2 At atmospheric pressure, 400 mm of SO4 is packed into a fixed-bed reactor with a diameter of 25 mm. 2-A Fe2O3-La2O3 / SBA-15 solid acid catalyst was used, with the preheating temperature adjusted to 60°C and the condensation temperature to 30°C. Under normal pressure, 500g of 4-methyl-4-[(3-methylbut-3-en-1-yl)oxy]-2-(2-methylprop-1-en-1-yl)oxacyclohexane and 500g of toluene were mixed and pumped into the preheater via an injection pump. After preheating, the mixture entered the catalyst bed. The reaction temperature was 140°C, and the flow rate was 30mL / min. The reactants were discharged from the bottom of the reactor and condensed to obtain 992g of mixed reaction liquid. GC analysis showed a feed conversion of 99.3% and a selectivity of 78%. Subsequently, 200Hg of toluene solvent was recovered, and high-vacuum distillation yielded 140g of isopentenol, resulting in 250g of nerol product with a GC content of 99.1% and a nerol yield of 78%.
[0031] Example 3 At atmospheric pressure, 600 mm of SO4 is packed into a fixed-bed reactor with a diameter of 25 mm. 2- A Fe2O3-La2O3 / SBA-15 solid acid catalyst was used, with the preheating temperature adjusted to 120°C and the condensation temperature to 50°C. At 200 kPa, 500 g of 4-methyl-4-[(3-methylbut-3-en-1-yl)oxy]-2-(2-methylprop-1-en-1-yl)oxacyclohexane and 250 g of toluene were mixed and pumped into the preheater via an injection pump. After preheating, the mixture entered the catalyst bed. The reaction temperature was 180°C, and the flow rate was 50 mL / min. The reactants were discharged from the bottom of the reactor and, after condensation, yielded 989 g of the mixed reaction liquid. GC analysis showed a feed conversion of 99.3% and a selectivity of 85%. Subsequently, the toluene solvent was recovered at 200 Hg, and high-vacuum distillation yielded 153 g of isopentenol, resulting in 271 g of nerol product with a GC content of 99.4% and a nerol yield of 85%.
[0032] Example 4 At atmospheric pressure, 500 mm of SO4 is packed into a fixed-bed reactor with a diameter of 25 mm. 2-A Fe2O3-La2O3 / SBA-15 solid acid catalyst was used, with the preheating temperature adjusted to 80°C and the condensation temperature to 40°C. At 170 kPa, 500 g of 4-methyl-4-[(3-methylbut-3-en-1-yl)oxy]-2-(2-methylprop-1-en-1-yl)oxacyclohexane and 250 g of 1,4-dioxane were mixed and pumped into the preheater via an injection pump. After preheating, the mixture entered the catalyst bed. The reaction temperature was 160°C, and the flow rate was 30 mL / min. The reactants were discharged from the bottom of the reactor and, after condensation, yielded 980 g of mixed reaction liquid. GC analysis showed a feed conversion of 99.5% and a selectivity of 80%. Subsequently, the 1,4-dioxane solvent was recovered at 200 Hg, and high-vacuum distillation yielded 144 g of isopentenol, resulting in 255 g of nerol product with a GC content of 99.0% and a nerol yield of 80%.
[0033] Example 5 At atmospheric pressure, 400 mm of SO4 is packed into a fixed-bed reactor with a diameter of 25 mm. 2- A Fe2O3-La2O3 / SBA-15 solid acid catalyst was used, with the preheating temperature adjusted to 60°C and the condensation temperature to 30°C. At 300 kPa, 500 g of 4-methyl-4-[(3-methylbut-3-en-1-yl)oxy]-2-(2-methylprop-1-en-1-yl)oxacyclohexane and 500 g of n-heptane were mixed and pumped into the preheater via an injection pump. After preheating, the mixture entered the catalyst bed. The reaction temperature was 200°C, and the flow rate was 20 mL / min. The reactants were discharged from the bottom of the reactor and, after condensation, yielded 986 g of mixed reaction liquid. GC analysis showed a feed conversion of 99.8% and a selectivity of 83%. Subsequently, the n-heptane solvent was recovered at 200 Hg, and high-vacuum distillation yielded 149 g of isopentenol, resulting in 265 g of nerol product with a GC content of 98.7% and a nerol yield of 83%.
[0034] Example 6 Based on implementation 3, the number of times the catalyst is reused is as follows: SO4 2- The Fe2O3-La2O3 / SBA-15 solid acid catalyst can be reused at least 5 times. When it is reused for the 5th batch (the catalyst is used for the 6th batch), the feed conversion rate decreases and the selectivity decreases more significantly. When it is reused for the 5th batch, the catalyst conversion rate is only 85% and the selectivity is 66%.
[0035] Number of times to apply Raw material conversion rate Neroli ether product selectivity 1 99.30% 85.70% 2 99.00% 85.40% 3 99.00% 84.80% 4 98.50% 83.30% 5 96.93% 82.80% 6 85.60% 66.0% The above description of the embodiments is only for illustrating the technical concept and features of the present invention. Its purpose is to enable those skilled in the art to understand the content of the present invention and implement it accordingly. Those skilled in the art can obviously easily make various modifications to these embodiments and apply the general principles described herein to other embodiments without creative effort. Therefore, the above embodiments should not be used to limit the scope of protection of the present invention. All improvements and modifications made by those skilled in the art based on the disclosure of the present invention without departing from the scope of the present invention should be covered within the scope of protection of the present invention.
Claims
1. A method for synthesizing nerol from 4-methyl-4-[(3-methylbut-3-en-1-yl)oxy]-2-(2-methylprop-1-en-1-yl)oxacyclohexane, characterized in that, The process includes the following steps: 4-methyl-4-[(3-methylbut-3-en-1-yl)oxy]-2-(2-methylprop-1-en-1-yl)oxacyclohexane is mixed uniformly with a solvent, preheated using a preheater, and then pumped into a container filled with SO4 at a certain flow rate. 2- The reaction was carried out in a fixed-bed reactor with Fe2O3-La2O3 / SBA-15 solid acid catalyst. The reaction was carried out at a certain temperature and pressure for a period of time. After the reaction, the crude product was obtained by cooling in a condenser. The crude product was then distilled to obtain nerol product and isopentenol byproduct. The SO4 2- In the Fe2O3-La2O3 / SBA-15 solid acid catalyst, the molar ratio of La to Fe is 1:8~10, the total loading of Fe2O3 and La2O3 is 1.5~4%, and the molar ratio of sulfate to ferric oxide on the surface of the solid acid catalyst is 1.5~1.
8.
2. The method for synthesizing nerol from 4-methyl-4-[(3-methylbut-3-en-1-yl)oxy]-2-(2-methylprop-1-en-1-yl)oxacyclohexane according to claim 1, characterized in that: The solvents used are toluene, cyclohexane, n-hexane, n-heptane, ethyl acetate, acetonitrile, tetrahydrofuran, ethylene glycol dimethyl ether, 1,4-dioxane, N,N-dimethylacetamide, N,N-diethylacetamide, N-methylpyrrolidone, N-ethylpyrrolidone, or water, or a mixture of two or more of these solvents.
3. A method for synthesizing nerol from 4-methyl-4-[(3-methylbut-3-en-1-yl)oxy]-2-(2-methylprop-1-en-1-yl)oxacyclohexane according to claim 1 or 2, characterized in that: The amount of solvent used is 0.2 to 3 times the mass of the raw material.
4. The method for synthesizing nerol from 4-methyl-4-[(3-methylbut-3-en-1-yl)oxy]-2-(2-methylprop-1-en-1-yl)oxacyclohexane according to claim 1, characterized in that: The preheating temperature is 60℃~120℃, the reaction temperature is 120℃~240℃, and the condenser temperature is 30℃~80℃.
5. The method for synthesizing nerol from 4-methyl-4-[(3-methylbut-3-en-1-yl)oxy]-2-(2-methylprop-1-en-1-yl)oxacyclohexane according to claim 1, characterized in that: The reaction pressure is 101 kPa to 550 kPa.
6. The method for synthesizing nerol from 4-methyl-4-[(3-methylbut-3-en-1-yl)oxy]-2-(2-methylprop-1-en-1-yl)oxacyclohexane according to claim 1, characterized in that: The feed flow rate is 10~80mL / min, and the residence time of the material in the reactor is 10s-200s.
7. The method for synthesizing nerol from 4-methyl-4-[(3-methylbut-3-en-1-yl)oxy]-2-(2-methylprop-1-en-1-yl)oxacyclohexane according to claim 1, characterized in that: The fixed-bed reactor has a diameter of 25 mm, the catalyst filling height is 400-800 mm, and the loading amount is 50-100 g.
8. The method for synthesizing nerol from 4-methyl-4-[(3-methylbut-3-en-1-yl)oxy]-2-(2-methylprop-1-en-1-yl)oxacyclohexane according to claim 1, characterized in that: The SO4 2- The Fe2O3-La2O3 / SBA-15 solid acid catalyst was prepared by the following steps: An equal volume of SBA-15 was impregnated in a mixed aqueous solution of lanthanum nitrate and ferric nitrate. After standing, the mixture was transferred to a hydrothermal reactor containing ethanol for hydrothermal reaction. Following the reaction, the mixture was dried and subjected to a first high-temperature treatment. The resulting powder was heated and stirred in an aqueous solution of (NH4)2SO4, then filtered, dried, and subjected to a second high-temperature treatment to obtain SO4. 2- -Fe2O3-La2O3 / SBA-15 solid acid catalyst.
9. The method for synthesizing nerol from 4-methyl-4-[(3-methylbut-3-en-1-yl)oxy]-2-(2-methylprop-1-en-1-yl)oxacyclohexane according to claim 8, characterized in that: The hydrothermal reaction is carried out at a temperature of 100-150℃ for 3-5 hours. And / or, the drying temperature is 100~120℃ and the time is 10~14h; And / or, the first high-temperature treatment process is as follows: heating to 500℃ in a muffle furnace at a rate of 2.5℃ / min and holding for 5 hours; And / or, the heating and stirring temperature is 70~90℃ and the stirring is carried out for 4~8 hours; And / or, the second high-temperature treatment process is as follows: heating to 550°C in a muffle furnace at a rate of 5°C / min and holding for 4 hours.