A method for preparing santal type compounds from sandalwood by-product

Abstract

The application belongs to the technical field of organic synthesis, and specifically discloses a method for preparing santali type compounds by taking by-products of sandalwood as raw materials. The by-products of sandalwood production, i.e. ether sandalwood derivatives 3-methyl-4-methoxy-1-(2,2,3-trimethyl-3-cyclopentenyl)-1,3-pentadiene, are recycled and utilized as raw materials to synthesize sandalwood 210 through a beta, gamma-unsaturated ketone intermediate 1, to synthesize black sandalwood alcohol through MPV reduction of the intermediate 1, and to obtain multi-sandalwood alcohol by methylating the intermediate 1 under alkaline conditions and then performing MPV reduction. The application realizes comprehensive utilization of by-products, turns waste into treasure, reduces the generation of solid waste, simultaneously realizes the preparation of high-value sandalwood series products, and has important economic and social benefits.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology and relates to the synthesis of sandalwood fragrance compounds, specifically to a method for preparing high-end sandalwood fragrance series products using sandalwood by-products as raw materials. Background Technology

[0002] Sandalwood 210: 3-Bornenyl-2-butanol, possesses a strong woody aroma, closely resembling natural sandalwood, and can bring a full, warm, and natural sandalwood character to fragrance formulations. Simultaneously, the aroma is highly expansive and long-lasting. When used in combination with ebony alcohol, it can serve as an effective substitute for the aroma of natural sandalwood. The chemical name of Sandalwood 210 is: 3-methyl-5-(2,2,3-trimethyl-3-cyclopentenyl)-pent-2-ol, with the chemical formula C2. 14 H 26 O, with a molecular weight of 210, is hence the name Sandalwood 210; Ebony alcohol: A pale yellow liquid with a strong sandalwood, woody, and musky aroma, used in cosmetic fragrance formulations. Its chemical name is 3-methyl-5-(2,2,3-trimethyl-3-cyclopentenyl)-4-penten-2-ol, and its chemical formula is C2. 14 H 24 O, with a molecular weight of 208.

[0003] Pyrosanol: A pale yellow to colorless liquid with a strong and long-lasting sandalwood aroma, widely used in cosmetic fragrances; its chemical name is 3,3-dimethyl-5-(2,2,3-trimethyl-3-cyclopentenyl)-4-penten-2-ol, and its chemical formula is C2. 15 H 26 O, with a molecular weight of 222; Polysantol was first synthesized and marketed by Firmenich under the trade name Polysantol. It is a rich and diffuse sandalwood fragrance, with a luxurious taste and high aroma intensity. Polysantol is a substance with very good affinity. It can produce a very diffuse sandalwood effect, and in perfumes using it, a true sandalwood characteristic scent can permeate the top, middle, and base notes.

[0004]

[0005] Existing methods for synthesizing sandalwood 210 include: (1) CN 101125798 B reports a three-step reaction to obtain 3-borneolenyl-2-butanol from borneolenaldehyde. First, borneolenaldehyde is used as a raw material and undergoes aldol condensation with butanone. Then, 3-borneolenyl-2-butanone, a fatty alcohol with 2-4 carbon atoms, a solid base, and a copper / chromium catalyst are reacted. Finally, a solvent and a reducing agent are added to the crude 3-borneolenyl-2-butanol to obtain the final product. This patent has disclosed a method for reducing αβ-unsaturated ketones with a metal catalyst and hydrogen. However, the intermediate reaction involved in this patent is incomplete and requires secondary reduction with the help of LiAlH4, NaBH4, etc. These easily explosive reducing agents pose safety risks and inevitably generate a large amount of wastewater.

[0006] (2) CN 119455953 A reported a high copper content zirconium dioxide supported catalyst and its preparation method and its application in the selective hydrogenation preparation of sandalwood 210. The patent prepared Cu / ZrO2 catalyst by low temperature co-precipitation of copper salt, zirconium source and a small amount of magnesium source and mild heat treatment. It showed good performance in the reduction of 3-pyroneinyl-2-butanone.

[0007] Existing methods for synthesizing ebony alcohol include: (1) CN 108752166 B reports a method for preparing ebony alcohol. In this method, santalone undergoes isomerization under the catalysis of zinc bromide. The reaction product and sec-butanol are then reacted with aluminum sec-butoxide to produce ebony alcohol. The raw material used in this patent is 3-phenylene-2-butanone synthesized via a conventional route. The patent innovatively uses zinc bromide as a catalyst to achieve double bond isomerization, and simultaneously employs an sec-butanol / aluminum sec-butoxide reduction method to reduce the carbonyl group, thus avoiding the use of sodium borohydride.

[0008] (2) CN 103483151 B reports a method of condensing methyl ethyl ketone with borneol to obtain 3-borneolenyl-2-butanone, followed by rearrangement of the double bond in dimethylamide solution via sodium methoxide catalysis to achieve double bond isomerization, and finally reduction with sodium borohydride to obtain ebony alcohol. This patent also starts from conventional borneol to obtain intermediates, and also uses sodium borohydride, a readily explosive reagent, which poses a safety risk and inevitably generates a large amount of wastewater.

[0009] Existing methods for synthesizing p-tanol include: (1) CN 103724161 B reports a method for preparing polysanol. Using borneol as a raw material, borneol and butanone undergo aldol condensation, followed by methylation under the action of a solid base and ionic liquid as phase transfer catalysts to obtain 3,3-dimethyl-5-(2,2,3-trimethyl-3-cyclopentenyl)-4-penten-2-one. Finally, it is reduced with sodium borohydride and distilled to obtain the final product. This patent also starts from conventional borneol to obtain an intermediate, optimizes the use of an ionic liquid as a phase transfer catalyst, and uses the easily explosive reagent sodium borohydride in the final reduction stage, posing a safety risk and inevitably generating a large amount of wastewater.

[0010] In summary, there are currently several reported methods for synthesizing sandalwood 210, ebony alcohol, and polystyrene alcohol, most of which start from borneol and butanone. These methods typically suffer from incomplete reduction, use of easily explosive reagents, and the generation of large amounts of wastewater. Summary of the Invention

[0011] To address the shortcomings of existing technologies, the present invention aims to provide a method for preparing sandalwood-scented compounds using sandalwood byproducts as raw materials. The raw material of the present invention is 3-methyl-4-methoxy-1-(2,2,3-trimethyl-3-cyclopentenyl)-1,3-pentadiene, which is a byproduct of sandalwood production. Starting from this substrate and passing through β,γ-unsaturated ketone intermediate 1, sandalwood 210, ebony alcohol, or polystannin alcohol can be synthesized. The present invention achieves comprehensive utilization of byproducts, turning waste into treasure, reducing the generation of solid waste, and simultaneously realizing the synthesis of high-value sandalwood-scented series products, which has significant economic and social benefits.

[0012] The reaction route of this invention is shown below:

[0013] This invention is achieved through the following technical solution: A method for preparing sandalwood-scented compounds using sandalwood by-products as raw materials includes the following steps: (1) Using 3-methyl-4-methoxy-1-(2,2,3-trimethyl-3-cyclopentenyl)-1,3-pentadiene as a raw material, a one-pot hydrolysis and rearrangement were carried out in an acidic solution to obtain 3-methyl-5-(2,2,3-trimethyl-3-cyclopentenyl)-4-pentenyl-2-one, which is referred to as intermediate 1; (2) Intermediate 1 was hydrogenated and reduced in the presence of a metal catalyst to obtain sandalwood 210.

[0014] Furthermore, the acid solution mentioned in step (1) is an aqueous solution of hydrochloric acid or an aqueous solution of sulfuric acid, and the mass ratio of the raw material to the acid solution is 1:(0.1-0.5). Furthermore, the mass concentration of the acid solution in step (1) is 20-50%; Furthermore, in step (1), the temperature of the one-pot reaction is 30℃-80℃, and the time is 2-5h.

[0015] Furthermore, the metal catalyst mentioned in step (2) is a Cu / SiO2 catalyst, wherein the Cu loading in the Cu / SiO2 catalyst is 5-30 wt%; Furthermore, in step (2), the mass ratio of intermediate 1 to the metal catalyst is 1:(0.001-0.05). Furthermore, the hydrogenation reduction in step (2) is carried out at a temperature of 120-180°C for 4-6 hours.

[0016] Furthermore, the present invention can also be implemented through the following technical solutions: A method for preparing sandalwood-scented compounds using sandalwood by-products as raw materials includes the following steps: (1) Using 3-methyl-4-methoxy-1-(2,2,3-trimethyl-3-cyclopentenyl)-1,3-pentadiene as a raw material, 3-methyl-5-(2,2,3-trimethyl-3-cyclopentenyl)-4-pentenyl-2-one was obtained by hydrolysis and rearrangement under acidic conditions, and it is referred to as intermediate 1; (2) Intermediate 1 was reduced by MPV to obtain ebony alcohol.

[0017] Furthermore, the acid solution mentioned in step (1) is an aqueous solution of hydrochloric acid or an aqueous solution of sulfuric acid, and the mass ratio of the raw material to the acid solution is 1:(0.1-0.5). Furthermore, the mass concentration of the acid solution in step (1) is 20-50%; Furthermore, in step (1), the temperature of the one-pot reaction is 30℃-80℃, and the time is 2-5h.

[0018] Furthermore, the catalyst used in the MPV reduction reaction in step (2) is aluminum isopropoxide, and the reducing agent used is isopropanol; the mass ratio of intermediate 1 to aluminum isopropoxide is 1:(0.01-0.05). Furthermore, the MPV reduction reaction in step (2) is carried out at a temperature of 80-90°C for 8-12 hours.

[0019] Furthermore, the present invention can also be implemented through the following technical solutions: A method for preparing sandalwood-scented compounds using sandalwood by-products as raw materials includes the following steps: (1) Using 3-methyl-4-methoxy-1-(2,2,3-trimethyl-3-cyclopentenyl)-1,3-pentadiene as a raw material, 3-methyl-5-(2,2,3-trimethyl-3-cyclopentenyl)-4-pentenyl-2-one was obtained by hydrolysis and rearrangement under acidic conditions, and it is referred to as intermediate 1; (2) Intermediate 1 was methylated with chloromethane under the catalysis of an alkaline catalyst to obtain 3,3-dimethyl-5-(2,2,3-trimethyl-3-cyclopentenyl)-4-pentenyl-2-one, which is referred to as intermediate 2. Intermediate 2 was reduced by MPV to obtain polytanol.

[0020] Furthermore, the acid solution mentioned in step (1) is an aqueous solution of hydrochloric acid or an aqueous solution of sulfuric acid, and the mass ratio of the raw material to the acid solution is 1:(0.1-0.5). Furthermore, the mass concentration of the acid solution in step (1) is 20-50%; Furthermore, the temperature of the one-pot reaction in step (1) is 30℃-80℃, and the time is 2-5h.

[0021] Furthermore, the alkaline catalyst mentioned in step (2) is one or a mixture of two or more of sodium hydroxide, potassium hydroxide, sodium tert-butoxide, potassium tert-butoxide, or sodium methoxide; Furthermore, in step (2), the mass ratio of intermediate 1 to alkaline catalyst is 1:(0.19-0.60); the molar ratio of intermediate 1 to chloromethane is 1:(1.0-1.2).

[0022] Furthermore, the catalyst used in the MPV reduction reaction in step (2) is aluminum isopropoxide, and the reducing agent used is isopropanol; the mass ratio of intermediate 1 to aluminum isopropoxide is 1:(0.01-0.05). Furthermore, the MPV reduction reaction in step (2) is carried out at a temperature of 80-90°C for 8-12 hours.

[0023] Compared with the prior art, the beneficial effects of the present invention are as follows: Compared with traditional synthesis methods, the method for synthesizing high-end sandalwood series products using sandalwood by-products provided by this invention achieves high conversion rates, and the catalyst can be recycled, reducing the use of organic solvents, reducing the generation of waste, and avoiding the use of easily explosive reagents. At the same time, it realizes the comprehensive utilization of by-products, turning waste into treasure, reducing the generation of solid waste, realizing the transformation of high-value sandalwood series products, and creating new economic and social benefits. Attached Figure Description

[0024] Figure 1This is the GC-MS spectrum of 3-methyl-4-methoxy-1-(2,2,3-trimethyl-3-cyclopentenyl)-1,3-pentadiene, the raw material of this invention. Detailed Implementation

[0025] This invention provides a method for preparing sandalwood-scented compounds using sandalwood byproducts as raw materials. In specific embodiments, unless otherwise specified, the experimental methods used are conventional methods, and the materials and reagents used are commercially available. The invention will now be described in detail with reference to specific embodiments.

[0026] The raw material used in this invention, 3-methyl-4-methoxy-1-(2,2,3-trimethyl-3-cyclopentenyl)-1,3-pentadiene, is a sandalwood byproduct. This byproduct is generated by the oxyalkylation of 3-methyl-5-(2,2,3-trimethyl-3-cyclopentenyl)-3-pentenyl-2-one with chloromethane, as determined by GC-MS (see [link to GC-MS]). Figure 1 The raw material has a molecular weight of 220 and is purified by distillation to a purity of 94%. In this invention, the raw material can be used directly.

[0027] In a specific embodiment of the present invention, the Cu / SiO2 catalyst used was provided by Shanghai Xunkai New Materials Technology Co., Ltd.

[0028] Example 1: Synthesis of Intermediate 1 100 g of 30% hydrochloric acid solution was added to the reactor and the temperature was controlled at 40℃. Then, 1000 g of 3-methyl-4-methoxy-1-(2,2,3-trimethyl-3-cyclopentenyl)-1,3-pentadiene was added dropwise to the reaction system over a period of 2-4 hours. The reaction was then maintained at this temperature for 1 hour until the raw material was completely converted. The mixture was allowed to stand and separate into layers. The lower aqueous phase was separated and could be recycled. The organic phase was washed and subjected to vacuum distillation to obtain 840 g of intermediate 1.

[0029] Example 2: Synthesis of Intermediate 1 100 g of 30% sulfuric acid solution was added to the reactor and the temperature was controlled at 40℃. Then, 1000 g of 3-methyl-4-methoxy-1-(2,2,3-trimethyl-3-cyclopentenyl)-1,3-pentadiene was added dropwise to the reaction system over a period of 2-4 hours. The reaction was then maintained at this temperature for 1 hour until the raw material was completely converted. The mixture was allowed to stand and separate into layers. The lower aqueous phase was separated and could be recycled. The organic phase was washed and subjected to vacuum distillation to obtain 843 g of intermediate 1.

[0030] Example 3: Synthesis of Sandalwood 210 Add 100 g of methanol solvent, 1000 g of intermediate 1, and 5 g of 15wt% Cu / SiO2 catalyst to the hydrogenation reactor. Seal the hydrogenation reactor, start stirring, and purge the reaction system with nitrogen three times, followed by purging with hydrogen three times. Raise the temperature to 170℃, control the hydrogen pressure at 30 bar, and maintain the temperature for 4-6 hours until the remaining intermediate 1 is less than 0.5%. Stop the reaction, filter the catalyst, and distill the organic phase under reduced pressure to obtain 990 g of sandalwood 210. Example 4: Synthesis of Ebonyl Alcohol Add 500 g of isopropanol and 20 g of aluminum isopropoxide to the reactor, heat to reflux, and then add 1000 g of intermediate 1 dropwise to the reaction system, controlling the dropwise addition time to 3-4 h. At the same time, adjust the reflux ratio to 9 (back): 3 (out) to recover the generated acetone. Stop the reaction when the content of intermediate 1 is less than 1%. Then, recover the excess isopropanol by vacuum distillation. Continue vacuum distillation to obtain 942 g of ebony alcohol.

[0031] Example 5: Synthesis of p-tanol 1000 g of DMAC was added to an autoclave, followed by 97 g of sodium hydroxide. The autoclave was sealed, and stirring was started. The temperature was controlled at 20°C. 500 g of intermediate 1 was added to a dropping vessel and then dropped into the reaction system over a period of 2 hours. After intermediate 1 was completely added, chloromethane gas was continuously introduced into the reaction system, and the reaction was maintained at this temperature for 3 hours before the reaction was stopped. DMAC was recovered by vacuum distillation. The organic phase after solvent removal was washed to remove sodium chloride. The remaining organic phase was then subjected to vacuum distillation to obtain 475 g of intermediate 2. Add 200 g of isopropanol and 8 g of aluminum isopropoxide to the reactor, heat to reflux, and then add 400 g of intermediate 2 dropwise to the reaction system, controlling the dropwise addition time to 3-4 h. At the same time, adjust the reflux ratio to 15 (back): 3 (out) to recover the generated acetone. Stop the reaction when the content of intermediate 2 is less than 1%. Then, recover the excess isopropanol by vacuum distillation. Continue vacuum distillation to obtain 375 g of polytanol.

[0032] 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 preparing sandalwood-scented compounds using sandalwood by-products as raw materials, characterized in that, Includes the following steps: (1) Using 3-methyl-4-methoxy-1-(2,2,3-trimethyl-3-cyclopentenyl)-1,3-pentadiene as a raw material, a one-pot hydrolysis and rearrangement were carried out in an acidic solution to obtain 3-methyl-5-(2,2,3-trimethyl-3-cyclopentenyl)-4-pentenyl-2-one, which is referred to as intermediate 1; (2) Intermediate 1 was hydrogenated and reduced in the presence of a metal catalyst to obtain sandalwood 210.

2. A method for preparing sandalwood-scented compounds using sandalwood by-products as raw materials, characterized in that, Includes the following steps: (1) Using 3-methyl-4-methoxy-1-(2,2,3-trimethyl-3-cyclopentenyl)-1,3-pentadiene as a raw material, 3-methyl-5-(2,2,3-trimethyl-3-cyclopentenyl)-4-pentenyl-2-one was obtained by hydrolysis and rearrangement under acidic conditions, and it is referred to as intermediate 1; (2) Intermediate 1 was reduced by MPV to obtain ebony alcohol.

3. A method for preparing sandalwood-scented compounds using sandalwood by-products as raw materials, characterized in that, Includes the following steps: (1) Using 3-methyl-4-methoxy-1-(2,2,3-trimethyl-3-cyclopentenyl)-1,3-pentadiene as a raw material, 3-methyl-5-(2,2,3-trimethyl-3-cyclopentenyl)-4-pentenyl-2-one was obtained by hydrolysis and rearrangement under acidic conditions, and it is referred to as intermediate 1; (2) Intermediate 1 was methylated with chloromethane under the catalysis of an alkaline catalyst to obtain 3,3-dimethyl-5-(2,2,3-trimethyl-3-cyclopentenyl)-4-pentenyl-2-one, which is referred to as intermediate 2. Intermediate 2 was reduced by MPV to obtain polytanol.

4. The method for preparing sandalwood-scented compounds using sandalwood by-products as raw materials according to claim 1, characterized in that: The acid solution mentioned in step (1) is an aqueous solution of hydrochloric acid or an aqueous solution of sulfuric acid, and the mass ratio of the raw material to the acid solution is 1:(0.1-0.5). The mass concentration of the acid solution is 20-50%; And / or, the temperature of a one-pot reaction is 30℃-80℃, and the time is 2-5h.

5. The method for preparing sandalwood-scented compounds using sandalwood by-products as raw materials according to claim 1, characterized in that: The metal catalyst mentioned in step (2) is a Cu / SiO2 catalyst, wherein the Cu loading in the Cu / SiO2 catalyst is 5-30 wt%. The mass ratio of intermediate 1 to the metal catalyst is 1:(0.001-0.05). And / or, the hydrogenation reduction is carried out at a temperature of 120-180°C for a time of 4-6 hours.

6. The method for preparing sandalwood-scented compounds using sandalwood by-products as raw materials according to claim 2, characterized in that: The acid solution mentioned in step (1) is an aqueous solution of hydrochloric acid or an aqueous solution of sulfuric acid, and the mass ratio of the raw material to the acid solution is 1:(0.1-0.5). The mass concentration of the acid solution is 20-50%; And / or, the temperature of a one-pot reaction is 30℃-80℃, and the time is 2-5h.

7. The method for preparing sandalwood-scented compounds using sandalwood by-products as raw materials according to claim 2, characterized in that: The catalyst used in the MPV reduction reaction in step (2) is aluminum isopropoxide, and the reducing agent used is isopropanol; the mass ratio of intermediate 1 to aluminum isopropoxide is 1:(0.01-0.05). And / or, the MPV reduction reaction is carried out at a temperature of 80-90°C for 8-12 hours.

8. The method for preparing sandalwood-scented compounds using sandalwood by-products as raw materials according to claim 3, characterized in that: The acid solution mentioned in step (1) is an aqueous solution of hydrochloric acid or an aqueous solution of sulfuric acid, and the mass ratio of the raw material to the acid solution is 1:(0.1-0.5). The mass concentration of the acid solution is 20-50%; And / or, the temperature of a one-pot reaction is 30℃-80℃, and the time is 2-5h.

9. The method for preparing sandalwood-scented compounds using sandalwood by-products as raw materials according to claim 3, characterized in that: The alkaline catalyst mentioned in step (2) is one or a mixture of two or more of sodium hydroxide, potassium hydroxide, sodium tert-butoxide, potassium tert-butoxide, or sodium methoxide; And / or, the mass ratio of intermediate 1 to alkaline catalyst is 1:(0.19-0.60); the molar ratio of intermediate 1 to chloromethane is 1:(1.0-1.2).

10. The method for preparing sandalwood-scented compounds using sandalwood by-products as raw materials according to claim 3, characterized in that: The catalyst used in the MPV reduction reaction in step (2) is aluminum isopropoxide, and the reducing agent used is isopropanol; the mass ratio of intermediate 1 to aluminum isopropoxide is 1:(0.01-0.05). And / or, the MPV reduction reaction is carried out at a temperature of 80-90°C for 8-12 hours.

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