Preparation method of synthetic perfume
By heating in formamidine acetate solvent and adding cashmereone in batches, combined with brine washing and vacuum distillation purification, the problems of green economy and high efficiency in the synthesis of sinofide fragrance molecules were solved, and high-yield fragrance preparation was achieved.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-12-26
- Publication Date
- 2026-04-03
AI Technical Summary
The existing synthesis process for Sinofide flavor molecules cannot simultaneously achieve greenness, economy, efficiency and high yield, and cannot support its large-scale, high-quality production.
A portion of formamidine acetate was dissolved in a solvent and heated and stirred to reflux temperature. Cashmereone and the remaining formamidine acetate were added in batches at regular intervals. After the reaction was completed, the mixture was washed with brine and purified by vacuum distillation to obtain the synthetic fragrance.
This improved reaction conversion rate and product selectivity, reduced purification difficulty, and enabled the preparation of synthetic fragrances with high yield and ease of industrial production.
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Figure CN121779341A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of fragrance and flavor technology, and specifically to a method for preparing synthetic fragrances. Background Technology
[0002] In the modern perfume industry, consumers' demands for the softness, envelopment, and versatility of fragrance notes continue to rise. Fragrance ingredients that can organically blend elements such as musk, amber, woody notes, and powdery notes have become one of the core directions for perfume formulation innovation. Sinofide, as a typical representative of this type of fragrance, has been widely used in the formulations of many mainstream perfumes such as "RoseMagnetic" and "Polo Ultra Blue" due to its unique fragrance characteristics. Its hydrogenated product, Ambertonic, is also a commonly used raw material in the perfume industry. Figure 1 The chemical structural formulas of cashmereone, sinofide, and their hydrogenation product Ambertonic are shown, as follows: Figure 1 As shown, this fragrance molecule is prepared by modifying the carbonyl group of cashmereone to a pyrimidine structure. It has high application value and market demand, but its current synthesis process still has many limitations and is difficult to match the industry's requirements for green, economical and efficient production. Developing a better sinofide synthesis process has become an important research and development direction in the fragrance field.
[0003] Currently, the industry has developed multiple technical routes for the synthesis of Sinofide and similar pyrimidine fragrance molecules: In 2006, Phil S. Baran first obtained the corresponding pyrimidine products by reacting ketones and formamidine acetate as raw materials and propanol as solvent in a one-pot reaction; In 2012, Givaudan Company first synthesized Sinofide molecules by adding five times the molar amount of formamidine acetate and n-butanol to cashmereone as raw material and refluxing at 130°C for 24 h, and then recrystallizing with ethanol after liquid chromatography or vacuum distillation; In 2015, a related research team used ketones and triazines as reactants and DMSO as solvent to generate corresponding pyrimidine compounds through reaction; In 2023, researchers synthesized a series of pyrimidine derivatives by adding ketones, ammonium acetate, and DMA-DMC to a reaction flask at the same time under the catalysis of ammonium iodide.
[0004] However, existing synthesis technologies have significant drawbacks: the one-pot method in 2006 required 20 times the molar amount of formamidinium acetate and a large amount of solvent, and the yield was only 73% when using tert-butylcyclohexanone as a raw material, resulting in high costs and resource consumption; the process for synthesizing Sinofide in 2012 had a yield of only 41%, indicating low production efficiency; the method in 2015 used expensive triazine raw materials and required the addition of triethylamine, increasing the complexity of post-processing; the catalytic synthesis method in 2023 required inert gas protection, had harsh reaction conditions, and had a conversion rate of only about 70%; overall, existing technologies cannot simultaneously meet the requirements of green economy, ease of operation, and high yield, and cannot efficiently support the large-scale, high-quality production of Sinofide fragrances.
[0005] In conclusion, given the wide range of applications of sinofide fragrance molecules, there is an urgent need to explore a green, economical, simple, efficient, and high-yield synthesis process to address the problems existing in current technologies. Summary of the Invention
[0006] To address the shortcomings and deficiencies of the existing technology, this invention provides a method for preparing synthetic fragrances. The preparation method provided by this invention has extremely high conversion rate, low purification difficulty, and yields a high-quality product with excellent application value, making it easy for industrial production.
[0007] One object of the present invention is to provide a method for preparing a synthetic fragrance, the method comprising the following steps: S1. Dissolve a portion of formamidine acetate in a solvent, heat and stir to reflux temperature and maintain for a certain time to obtain the reaction system; S2. At constant temperature, cashmereone is added to the reaction system, and then the remaining formamidine acetate is added. The reaction is maintained at this temperature. After the reaction is completed, the temperature is lowered and the product is discharged to obtain the crude product. S3. The crude product is washed with brine and purified by vacuum distillation to obtain the synthetic fragrance.
[0008] Furthermore, the solvent is selected from one or more of butanol, pentanol, and tert-pentanol.
[0009] Further, in step S1, the mass ratio of the partial formamidine acetate to the solvent is 1:(1-5).
[0010] Furthermore, in step S1, the heating temperature is 100-160℃.
[0011] Preferably, in step S1, the heating temperature is 120-140℃.
[0012] Furthermore, in step S1, the heating and stirring time is 10-60 min.
[0013] Preferably, in step S1, the heating and stirring time is 20-40 min.
[0014] Furthermore, in step S2, the time interval for replenishment is 1-4 hours, and the number of times is 1-6.
[0015] Preferably, in step S2, the time interval for replenishment is 1-2 hours, and the number of times is 1-3.
[0016] Furthermore, the mass ratio of the partial formamidine acetate to cashmereone is (2-3):1.
[0017] Further, in step S2, the mass ratio of cashmereone to the remaining formamidin acetate is 1:(1-3).
[0018] Preferably, in step S2, the mass ratio of cashmereone to the remaining formamidin acetate is 1:(2-3).
[0019] Furthermore, in step S3, the vacuum degree of the reduced pressure distillation is 50-300 Pa, and the distillation temperature is 110-160℃.
[0020] Preferably, in step S3, the vacuum degree of the reduced pressure distillation is 120-200 Pa, and the distillation temperature is 120-140℃.
[0021] The present invention has the following beneficial effects: This invention provides a method for preparing a synthetic fragrance. The method is as follows: a portion of formamidine acetate is dissolved in a solvent, heated and stirred to reflux temperature and maintained for a certain time. This operation activates the "amidine group activity" of formamidine acetate, making the subsequent carbonyl addition with cashmereone more efficient, thereby improving the reaction conversion rate. Subsequently, cashmereone is added to the reaction system, and the remaining formamidine acetate and solvent are added in batches at regular intervals to avoid side reactions caused by exothermic reactions or in-process reactions, thereby improving the selectivity of the product. The reaction is kept at a constant temperature, and after the reaction is completed, the product is cooled and discharged to obtain a crude product. Because the preparation method of this invention has a high conversion rate and high product selectivity, the purification difficulty is greatly reduced. The crude product only needs to be washed with brine and purified by vacuum distillation to obtain the synthetic fragrance. Attached Figure Description
[0022] Figure 1 The chemical structural formulas of cashmereone, sinofide, and their hydrogenation product Ambertonic are shown.
[0023] Figure 2 The synthetic fragrance prepared in Example 3 is shown. 1 H NMR spectrum. Detailed Implementation
[0024] To more clearly illustrate the technical solution of the present invention, the following embodiments are provided. Unless otherwise stated, the raw materials, reactions, and post-processing methods appearing in the embodiments are all commercially available raw materials and technical methods well known to those skilled in the art.
[0025] The terms "preferred," "more preferably," and "more suitable" used in this invention refer to embodiments of the invention that provide certain beneficial effects under certain circumstances. However, other embodiments may also be preferred under the same or other circumstances. Furthermore, the description of one or more preferred embodiments does not imply that other embodiments are unavailable, nor is it intended to exclude other embodiments from the scope of this invention.
[0026] It should be understood that, except in any operational instance or otherwise indicated, the amounts or all figures representing ingredients used, for example, in the specification and claims, should be understood to be modified by the term "about" in all cases. Therefore, unless otherwise stated, the numerical parameters set forth in the following specification and appended claims are approximate values varying according to the desired performance to be obtained according to the invention.
[0027] In embodiments of the present invention, the following raw materials will be used: Salt water, saturated salt water.
[0028] Unless otherwise specified, the water used in the embodiments of this invention refers to ordinary water.
[0029] In the embodiments of this invention, "parts" refers to parts by mass.
[0030] Example 1 A method for preparing a synthetic fragrance, the method comprising the following steps: S1. Add 62.4 g of formamidine acetate and 300 mL of n-butanol to the two-necked flasks respectively, and heat and stir at 130°C for 0.5 h to obtain the reaction system; S2. At constant temperature, 30.9 g of cashmereone was added to the reaction system. After 2 h, 62.4 g of formamidin acetate was added, and the reaction was continued at this temperature for 15.5 h. After cooling to room temperature, the product was discharged to obtain the crude product. S3. The crude product is washed three times with brine to remove the solvent, and then subjected to vacuum distillation at 140 Pa and 130 °C to obtain the synthetic fragrance.
[0031] Example 2 A method for preparing a synthetic fragrance, the method comprising the following steps: S1. Add 62.4 g of formamidine acetate and 150 mL of n-butanol to the two-necked flasks respectively, and heat and stir at 130°C for 0.5 h to obtain the reaction system; S2. At constant temperature, 30.9 g of cashmereone was added to the reaction system. After 2 h, 62.4 g of formamidin acetate and 150 mL of n-butanol were added. The reaction was continued at constant temperature for 15.5 h. After cooling to room temperature, the product was discharged to obtain the crude product. S3. The crude product is washed three times with brine to remove the solvent, and then subjected to vacuum distillation at 140 Pa and 130 °C to obtain the synthetic fragrance.
[0032] Example 3 A method for preparing a synthetic fragrance, the method comprising the following steps: S1. Add 62.4 g of formamidine acetate and 150 mL of n-butanol to the two-necked flasks respectively, and heat and stir at 130°C for 0.5 h to obtain the reaction system; S2. At constant temperature, 30.9 g of cashmereone was added to the reaction system. After an interval of 2 h, 31.2 g of formamidine acetate and 75 mL of n-butanol were added to the reaction system. After an interval of 2 h, another 31.2 g of formamidine acetate and 75 mL of n-butanol were added to the reaction system. The reaction was then continued at this temperature for 13.5 h. After cooling to room temperature, the product was discharged to obtain the crude product. S3. The crude product is washed three times with brine to remove the solvent, and then subjected to vacuum distillation at 140 Pa and 130 °C to obtain the synthetic fragrance.
[0033] Figure 2 The synthetic fragrance prepared in Example 3 is shown. 1 H NMR spectrum, by Figure 2 It is known that the method for preparing synthetic fragrance provided by the present invention can successfully produce Sinfonide fragrance with fewer impurity peaks and higher product purity.
[0034] Comparative Example 1 A method for preparing a synthetic fragrance, the method comprising the following steps: S1. Add 73 g of formamidine acetate, 30.9 g of cashmereone, and 300 mL of n-butanol to the two-necked flasks respectively, and heat to 130℃ to obtain the reaction system; S2. At constant temperature, after 6 hours, 51.8 g of formamidine acetate was added to the reaction system, and the reaction was continued at this temperature for another 12 hours. After cooling to room temperature, the product was discharged to obtain the crude product. S3. The crude product is washed three times with brine to remove the solvent, and then subjected to vacuum distillation at 140 Pa and 130 °C to obtain the synthetic fragrance.
[0035] Comparative Example 2 A method for preparing a synthetic fragrance, the method comprising the following steps: S1. Mix 10 g cashmereone, 27 g formamidine acetate and 50 mL n-butanol in a two-necked flask, heat to 118℃ and react for 22 h to obtain crude product; S2. The crude product is washed three times with brine to remove the solvent, and then subjected to vacuum distillation at 140 Pa and 130 °C to obtain the synthetic fragrance.
[0036] Comparative Example 3 A method for preparing a synthetic fragrance, the method comprising the following steps: S1. Mix 10 g cashmereone, 108 g formamidine acetate and 350 mL n-butanol in a two-necked flask, heat to 130℃ and react for 22 h to obtain crude product; S2. The crude product is washed three times with brine to remove the solvent, and then subjected to vacuum distillation at 140 Pa and 130 °C to obtain the synthetic fragrance.
[0037] Test Example 1 The gas phase conversion rate of the synthetic fragrances prepared by the methods of Examples 1-3 and Comparative Examples 1-3 was tested.
[0038] The gas chromatography parameters were set as follows: an Agilent 19091B-105 column (50 m * 200 μm * 0.33 μm) was used. The initial temperature was 50°C, held for 1 min; the temperature was increased to 80°C at a rate of 8°C / min, held for 2 min; then increased to 200°C at a rate of 2°C / min, held for 2 min; then increased to 230°C at a rate of 8°C / min; then increased to 280°C at a rate of 20°C / min, held for 15 min. The system was set to split flow, with a carrier gas flow rate of 20 mL / min. The temperatures of the injection port and detector were both set to 280°C. In the preparation methods of the synthetic fragrances in Examples 1-3 and Comparative Examples 1-3, the mixture after solvent removal in step S2 or S3 was sampled and injected into a gas chromatograph for cashmereone conversion analysis.
[0039] The test results are shown in Table 1.
[0040] Table 1. Results of gas phase conversion rate test As shown in Table 1, in Comparative Examples 2 and 3, despite increasing the temperature and the amount of formamidine acetate, the conversion rate remained very low when formamidine acetate and cashmereone were added all at once. Because cashmereone and sinfonide have similar polarities, existing purification methods require column chromatography or vacuum distillation followed by recrystallization, increasing the cost of post-processing. In contrast, the purification method of this invention only requires brine washing and vacuum distillation. As can be seen from Example 1 and Comparative Example 1, prioritizing the addition of formamidine acetate to the reaction flask and heating to reflux before adding cashmereone can increase the conversion rate from 58.4% to 84.5%. In addition, by comparison, adding formamidine acetate and n-butanol in batches can greatly improve the conversion rate. Finally, in Example 3, by adding formamidine acetate in three batches, the conversion rate of cashmereone reached 100%, and the yield reached 90%. The amount of formamidine acetate used was only 4 times that of cashmereone. This has good application significance for the large-scale, high-quality production of Sinfonide.
[0041] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the invention can be implemented in other specific forms without departing from the spirit or essential characteristics of the invention. Therefore, the embodiments should be considered in all respects as exemplary and non-limiting, and the scope of the invention is defined by the appended claims rather than the foregoing description. Thus, it is intended that all variations falling within the meaning and scope of equivalents of the claims be included within the present invention.
[0042] Furthermore, it should be understood that although this specification describes embodiments, not every embodiment contains only one independent technical solution. This narrative style is merely for clarity. Those skilled in the art should consider the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.
Claims
1. A method for preparing a synthetic fragrance, characterized in that, The preparation method of the synthetic fragrance includes the following steps: S1. Dissolve a portion of formamidine acetate in a solvent, heat and stir to reflux temperature and maintain for a certain time to obtain the reaction system; S2. At constant temperature, cashmereone is added to the reaction system, and then the remaining formamidine acetate is added. The reaction is maintained at this temperature. After the reaction is completed, the temperature is lowered and the product is discharged to obtain the crude product. S3. The crude product is washed with brine and purified by vacuum distillation to obtain the synthetic fragrance.
2. The method for preparing synthetic fragrance according to claim 1, characterized in that, The solvent is selected from one or more of butanol, pentanol, and isoamyl alcohol.
3. The method for preparing synthetic fragrance according to claim 1, characterized in that, In step S1, the mass ratio of the partial formamidine acetate to the solvent is 1:(1-5).
4. The method for preparing synthetic fragrance according to claim 1, characterized in that, In step S1, the heating temperature is 100-160℃.
5. The method for preparing synthetic fragrance according to claim 1, characterized in that, In step S1, the heating and stirring time is 10-60 min.
6. The method for preparing synthetic fragrance according to claim 1, characterized in that, In step S2, the time interval for replenishment is 1-4 hours, and the number of times is 1-6.
7. The method for preparing synthetic fragrance according to claim 1, characterized in that, The mass ratio of formamidine acetate to cashmereone is (2-3):
1.
8. The method for preparing synthetic fragrance according to claim 1, characterized in that, In step S2, the mass ratio of cashmereone to the remaining formamidin acetate is 1:(1-3).
9. The method for preparing synthetic fragrance according to claim 1, characterized in that, In step S3, the vacuum degree of the reduced pressure distillation is 50-300 Pa, and the distillation temperature is 110-160℃.