A method for synthesizing β-tradyone

Abstract

This invention belongs to the field of organic synthesis and discloses a method for synthesizing β-daemon. The method uses readily available commercial β-cyclocitral I as the starting material, which undergoes an MBH reaction (Morita-Baylis-Hillman reaction) with crotonic acid (ester) to generate a hydroxyl intermediate II. Hydroxyl intermediate II is then oxidized to generate the corresponding ketone intermediate III, and finally, a decarboxylation reaction yields the final product, β-daemon. This method has advantages such as a short synthetic route, simple operation, low cost, easy product separation and purification, and no environmental pollution, and has high prospects for industrial application.

Description

Technical Field

[0001] This invention relates to the field of organic chemistry, and more specifically, to a method for synthesizing a type of β-turatone. Background Technology

[0002] β-Turkeyone is a safe food flavoring recognized by the American Food Flavor and Extract Manufacturers Association (FEMA No. 3243) and is also a permitted synthetic food flavoring in the appendix of my country's National Food Additives Standard GB2760-1996. β-Turkeyone has an extremely low aroma threshold and excellent aroma diffusion; therefore, only a small amount is needed in flavor formulations to significantly enhance the aroma. Generally, β-Turkeyone is prepared as a 10% solution before being used in flavor formulations. It is used in rose-scented fragrances and to develop fruity top notes. It can be added not only to high-end perfumes, cosmetics, soaps, detergents, and room fresheners, but also to the formulation of edible flavorings such as rose and kiwi.

[0003] The synthesis of β-drakhone is complex, but its aroma value is extremely high, attracting the attention of fragrance chemists and showing great development potential. Currently, some companies are already capable of mass-producing β-drakhone. However, due to the harsh reaction conditions, long process flow, and high synthesis difficulty, the synthesis technology still needs further development. Considering the abundant Litsea cubeba oil resources in China, this paper proposes using β-cyclocitral isolated from Litsea cubeba oil to synthesize β-drakhone. This synthetic route allows for the deep processing of Litsea cubeba oil, increasing the added value of the product.

[0004] Most reported synthetic methods for synthesizing β-turethane using β-cyclocitral as a starting material involve reacting β-citral with a propenyl Grignard reagent, followed by oxidation of the product to obtain β-turethane. While this route involves fewer reaction steps, the Grignard reagents are expensive and require further preparation. Furthermore, the Grignard reaction conditions are relatively harsh, the operation is cumbersome, and the safety is low, making it unsuitable for industrial production.

[0005]

[0006] Therefore, developing a synthetic method that uses β-cyclic citral as a raw material, has high economic value, a high safety factor, and is simple to operate, to prepare β-turatone has high prospects for industrial application. Summary of the Invention

[0007] To overcome the aforementioned technical deficiencies, this invention provides a novel method for preparing β-daemon. Starting with commercially available cyclocitral and crotonate, an MBH reaction is performed to generate a hydroxyl intermediate II. Intermediate II is oxidized to generate the corresponding ketone intermediate III, and finally, a decarboxylation reaction yields the final product, β-daemon. This method features a short synthetic route, simple operation, low cost, and easy product separation and purification, making it highly promising for industrial applications.

[0008] The objective of this invention can be achieved through the following technical solution: a method for synthesizing β-turatone, the synthetic route of which is shown below:

[0009] Includes the following steps: a. Using β-cyclocitral I and crotonic acid / ester as raw materials, an alcohol intermediate II was obtained by reacting under the catalysis of an organic base; b. Alcohol intermediate II reacts in the presence of an oxidizing agent to give ketone intermediate III; c. Ketone intermediate III reacts in the presence of a decarboxylating agent to give the final product β-Turkeyone.

[0010] Further, the catalyst mentioned in step a is an organic base, which is at least one of DABCO, DBU, DIPEA, DMAP, etc., preferably DABCO; the amount of catalyst added is 15-20% of the mass of β-cyclocitral, calculated based on the mass of the raw material cyclocitral.

[0011] Furthermore, the reaction solvent in step a is selected from dichloromethane, tetrahydrofuran, acetonitrile, tert-butyl methyl ether, etc., with acetonitrile being preferred.

[0012] Further, the oxidant in step b is one or more of active manganese dioxide, DMSO / oxalyl chloride, DMSO / thionyl chloride, etc.; the molar ratio of the oxidant to intermediate II is 1.5-3:1; preferably 2:1.

[0013] Further, the decarboxylating agent in step c is one of lithium chloride, sodium chloride, hydrochloric acid, etc., preferably sodium chloride; the amount of the decarboxylating agent is 10-30% of the mass of intermediate III, preferably 25%, calculated based on the mass of intermediate III. Beneficial effects of the invention

[0014] The present invention uses inexpensive raw materials, has a high yield, produces products without isomers, has high purity, and requires simple reaction conditions and a simple process route, thus having potential industrial application prospects. Attached Figure Description

[0015] Figure 1 The ¹H NMR spectrum of β-turatone obtained in Example 6; Figure 2 The image shows the LC-MS spectrum of β-turatone obtained in Example 6. Detailed Implementation

[0016] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0017] Example 1: Preparation of hydroxyl intermediate II (R=Me) In a three-necked flask equipped with a stirrer, thermometer, and dropping funnel, 100.0 g of β-cyclocitral, 73.0 g of methyl crotonate, 800 mL of dichloromethane, and 20.0 g of DABCO were added. The mixture was stirred at room temperature for 24 h. After the reaction was complete, the mixture was extracted twice with 500 mL of water and 300 mL of dichloromethane (300 mL x 2). The combined organic phases were washed with 100 mL of dilute hydrochloric acid and 50 mL of saturated brine. Dichloromethane was recovered by vacuum distillation. The organic phase was concentrated and evaporated to dryness to obtain 160 g of crude alcohol intermediate II (R=Me) with a purity of 96% (GC) and a yield of 96.5%. LC-MS (ESI) m / z calcd for C 15 H 25 O3 + [M+H] + 253.1798, found 253.1801.

[0018] Example 2: Preparation of hydroxyl intermediate II (R=H) In a three-necked flask equipped with a stirrer, thermometer, and dropping funnel, 100.0 g of β-cyclocitral, 62.0 g of crotonic acid, 800 mL of dichloromethane, and 20.0 g of DABCO were added. The mixture was stirred at room temperature for 24 h. After the reaction was complete, 500 mL of water was added, the pH was adjusted to 2-3 with dilute hydrochloric acid, and the mixture was extracted twice with 300 mL of dichloromethane. The combined organic phases were washed with 100 mL of dilute hydrochloric acid and then with 50 mL of saturated brine. Dichloromethane was recovered by vacuum distillation. The organic phase was concentrated and evaporated to dryness to obtain 157 g of crude alcohol intermediate II (R=H). After recrystallization from petroleum ether and ethyl acetate v / v = 5 / 1, 145.3 g of crude intermediate II was obtained, with a purity of 95% (GC) and a yield of 92%. LC-MS (ESI) m / z calcd for C 14 H 23 O3 + [M+ H] + 239.1642, found 239.1653.

[0019] Example 3: Preparation of ketone intermediate III (R=Me) In a three-necked flask equipped with a stirrer, thermometer, and dropping funnel, 120 g of intermediate II (R=Me) from Example 1, 800 mL of dichloromethane, and 82.9 g of activated manganese dioxide were added. The mixture was stirred and reacted at room temperature for 10 h. After the reaction was complete, the manganese dioxide was removed by filtration, and the filtrate was concentrated to dryness to obtain 112 g of intermediate III (R=Me) with a purity of 94% (GC) and a yield of 94%. LC-MS (ESI) m / z calcd for C 15 H 23 O3 + [M+H] + 251.1642, found 251.1680.

[0020] Example 4: Preparation of ketone intermediate III (R=H) In a three-necked flask equipped with a stirrer, thermometer, and dropping funnel, 120 g of intermediate II (R=H) from Example 2, 800 mL of dichloromethane, and 87.7 g of activated manganese dioxide were added. The mixture was stirred and reacted at room temperature for 10 h. After the reaction was complete, the manganese dioxide was removed by filtration, and the filtrate was concentrated to dryness to obtain 113 g of intermediate III (R=H) with a purity of 95% (GC) and a yield of 95%. LC-MS (ESI) m / z calcd for C 14 H 21 O3 + [M+H] + 237.1485., found 237.1496.

[0021] Example 5: Preparation of β-Turkeyone In a three-necked flask equipped with a stirrer, thermometer, and dropping funnel, 100.0 g of intermediate III (R=Me) from Example 3, 300 mL of DMSO, and 25 g of sodium chloride were added. The mixture was stirred at 150 °C for 6 h. After the reaction was complete, the DMSO was recovered by vacuum distillation. The crude product was extracted twice with 500 mL of water and 300 mL of ethyl acetate (300 mL x 2). The combined organic phases were washed with 100 mL of dilute hydrochloric acid and 50 mL of saturated brine. The ethyl acetate was recovered by vacuum distillation. The organic phase was concentrated and evaporated to dryness to obtain 85 g of crude β-turatone. The crude product was then purified by distillation to obtain 70.6 g of β-turatone with a purity of 98% and a yield of 92%.

[0022] Example 6: Preparation of β-Turkeyone In a three-necked flask equipped with a stirrer, thermometer, and dropping funnel, 100.0 g of intermediate III (R=H) from Example 4, 300 mL of ethanol, and 25 mL of concentrated hydrochloric acid were added. The mixture was stirred under reflux for 12 h. After the reaction was complete, the ethanol was recovered by vacuum distillation. The crude product was extracted twice with 500 mL of water and 300 mL of ethyl acetate (300 mL x 2). The combined organic phases were washed with 100 mL of dilute hydrochloric acid and 50 mL of saturated brine. Ethyl acetate was recovered by vacuum distillation to obtain 91 g of crude β-turatone. The crude product was then purified by distillation to obtain 74.0 g of β-turatone with a purity of 99% and a yield of 91%. 1 H NMR (400 MHz, CDCl3): δ 6.71 (dq, J =15.6, 6.8 Hz, 1H), 6.13 (dd, J = 15.6, 1.6 Hz, 1H), 1.97 (t, J = 6.8 Hz, 2H), 1.90 (dd, J m / z = 193.1609.

[0023] The above description is merely an example and illustration of the present invention. Those skilled in the art can make various modifications or additions to the specific embodiments described, or use similar methods to replace them, as long as they do not deviate from the invention or exceed the scope defined in the claims, they should all fall within the protection scope of the present invention.

Claims

1. A method for synthesizing β-tramyzone, characterized in that, Includes the following steps: ； a. Using β-cyclocitral I and crotonic acid / ester as raw materials, an alcohol intermediate II was obtained by reacting under the catalysis of an organic base; b. Alcohol intermediate II reacts in the presence of an oxidizing agent to give ketone intermediate III; c. Ketone intermediate III reacts in the presence of a decarboxylating agent to give the final product β-Turkeyone.

2. The method for synthesizing β-turatone according to claim 1, characterized in that: In step a, the organic base is at least one of DABCO, DBU, DIPEA, and DMAP.

3. The method for synthesizing β-turatone according to claim 1, characterized in that: In step a, the catalyst is 15-20% of the mass of β-cyclocitral.

4. The method for synthesizing β-drakone according to claim 1, characterized in that: In step a, the reaction solvent is selected from dichloromethane, tetrahydrofuran, acetonitrile, or tert-butylmethyl ether.

5. The method for synthesizing β-turatone according to claim 1, characterized in that: In step b, the oxidant is at least one of active manganese dioxide, DMSO / oxalyl chloride, DMSO / thionyl chloride, and chromium trioxide.

6. The method for synthesizing β-turatone according to claim 1, characterized in that: In step b, the molar ratio of the oxidant to intermediate II is 1.5-3:

1.

7. The method for synthesizing β-turatone according to claim 1, characterized in that: In step c, the decarboxylating agent is selected from lithium chloride, sodium chloride, or hydrochloric acid.

8. The method for synthesizing β-drakone according to claim 1, characterized in that: In step c, the amount of decarboxylating agent used is 10-30% of the mass of intermediate III.

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