A kind of preparation method of citronella nitrile

Abstract

The invention discloses a method for preparing citronellal. The method uses citronellal as a starting material and performs oximation and dehydration reactions in one pot to prepare citronellal. The synthesis method of the invention does not use dimethyl sulfoxide, does not produce dimethyl sulfide with an unpleasant odor, and performs oximation and dehydration in one pot, which significantly saves process operations and improves production efficiency. The recycling of sulfoxide reagents further reduces production costs, and the yield of preparing citronellal can reach more than 96%.

Description

Technical Field

[0001] The present application belongs to the technical field of preparation of flavors and fragrances, and specifically relates to a method for preparing citronellal nitrile from citronellal. Background Art

[0002] Citronella nitrile, scientific name is 3,7-dimethyl-6-octene-1-nitrile, its structural formula is It is one of the important nitrile fragrances with the aroma of lemon fruit and green tea. The fragrance is strong and lasting, safe and harmless to human skin, and can also repel mosquitoes. It is particularly suitable for the formulation of soap flavors and detergent flavors, and is also suitable for flavoring other daily chemical products. It is a nitrile fragrance with great development value.

[0003] Citronellal is one of the main components of plant essential oils such as citronella oil and eucalyptus oil. Using natural resource citronellal to synthesize citronellyl nitrile is the main method for synthesizing citronellyl nitrile. The process for preparing citronellal nitrile from citronellal mainly adopts the hydroxylamine oximation method, that is, citronellal oxime is prepared by reacting citronellal with hydroxylamine under alkaline conditions, and then citronellal nitrile is prepared in the presence of various dehydrating agents such as acetic anhydride (Liaoning Chemical Industry, Vol. 36, No. 11, pp. 758-760, 2007; Flavour Fragr. J. 2004; 19: 121-133), carrier base KOH-Al2O3 (Fine Chemical Intermediates, Vol. 33, No. 6, pp. 41-42, 2003), phase transfer catalyst PEG-400 (Guangxi Chemical Industry, Vol. 29, No. 2, pp. 4-6, 2000), DMSO / oxalyl chloride ("Synthesis Research of Nitrile Flavor Compounds and Application of Related Synthesis Methods", Lan Liyuan, Master's Thesis of Beijing Technology and Business University), SO2F2 (J. Org. Chem. 84, 5803-2812), etc. Although these methods can achieve relatively excellent yields of the target product, they require a two-step process and are cumbersome to operate. In addition, the DMSO used therein generates dimethyl sulfide with a foul odor after the reaction, while SO2F2 is a colorless, odorless, toxic gas and a potent greenhouse gas. There are safety hazards and environmental hazards, and they are not suitable for industrial production.

[0004] The one-step method for preparing citronellal from citronellal often requires expensive catalytic reaction systems and complicated operations, such as microwave / phase transfer / grinding (Chemical World, Issue 9, Pages 542-545, 2008), metal catalyst / NH3 / oxidant (CN104529822A), O-trifluoromethylbenzoylhydroxylamine / camphorsulfonic acid (Org. Lett., 2015, 17, 5064-5067) and Ru(OH) x / Al2O3 / NH3 (Top Catal (2010) 53:479–486), and the yields of these methods are generally around 80%-90%. In the one-step synthesis method for preparing fatty nitriles from fatty aldehydes under simple reaction conditions, such as hydroxylamine / hydrochloric acid / ethanol (Canadian Journal of Chemistry, vol45, p1015, 1967), DMSO / hydroxylamine (Sythetic Communications, 39:3601-3606, 2009), and the method of combining the above two-step synthesis method into a one-pot method ("Synthesis Research of Nitrile Flavor Compounds and Application of Related Synthesis Methods", Lan Liyuan, Master's Thesis of Beijing Technology and Business University), according to the inventor's experiments and prior art research results, when applied to the preparation of citronellal from citronellal, the reaction process is slow and complex mixed products are produced, and the yield of citronellal is extremely low.

[0005] Therefore, developing a method for preparing citronellal nitrile from citronellal with high production efficiency, low cost, safe and green production environment, and high product purity and yield is a technical problem that still needs to be solved in the field. Summary of the invention

[0006] The object of the present invention is to solve the above problems existing in the prior art and provide a method for preparing citronellal nitrile from citronellal with high production efficiency, low cost, safe and environmentally friendly production environment, and high product purity and yield. By improving the reaction system, the oximation and dehydration reactions can be carried out in one pot, and no dimethyl sulfide is produced, and the sulfoxide reagent can be recycled.

[0007] According to a method for preparing citronellal nitrile from citronellal provided by the present invention, the technical scheme is as follows:

[0008] Citronellal is used as a raw material, hydroxylamine hydrochloride, sulfoxide reagent, organic base and ethanol solvent are added, stirred and reacted at room temperature to 50°C for 0.5 to 4 hours, then heated to 60 to 100°C and kept warm for 0.5 to 1 hour, and citronellal nitrile is obtained after post-treatment. The reaction formula is as follows:

[0009]

[0010] Wherein, the sulfoxide reagent is: 4-(2-(2-(methylsulfoxide)ethyl)-4-nitrobenzene)morpholine, and its structural formula is as follows:

[0011]

[0012] According to the aforementioned method of the present invention, the organic base is any one of trimethylamine, triethylamine, tributylamine, and pyridine, or a combination thereof, preferably triethylamine.

[0013] According to the aforementioned method of the present invention, the molar ratio of citronellal, hydroxylamine hydrochloride, sulfoxide reagent and organic base is 1:1-3:0.01-0.5:2-5; preferably 1:2:0.1:3.

[0014] According to the aforementioned method of the present invention, the reaction temperature of the stirring reaction is preferably 40-50°C, more preferably 45°C, and the reaction time of the stirring reaction is preferably 1 to 3 hours, more preferably 2 hours.

[0015] According to the aforementioned method of the present invention, the temperature is raised to 80-90° C. and maintained for 0.5 hour.

[0016] According to the aforementioned method of the present invention, the post-treatment operation is as follows: adding an appropriate amount of water to the reaction solution for quenching, adding dilute hydrochloric acid to adjust the pH to 2-4, extracting with dichloromethane, and drying, concentrating, and separating the organic phase by silica gel column chromatography to obtain citronellal; adding sodium hydroxide to the aqueous phase to adjust the pH to 9-11, extracting with dimethane, and concentrating to obtain the sulfide of the reduction product of the sulfoxide reagent, dissolving the sulfide in ethanol, adding 30% hydrogen peroxide dropwise, stirring at room temperature for 2 hours, and obtaining the sulfoxide reagent 4-(2-(2-(methylsulfoxide)ethyl)-4-nitrobenzene)morpholine, which can be used for the next batch reaction.

[0017] Compared with the prior art, the present invention has the following significant beneficial effects:

[0018] (1) The method for preparing citronellal nitrile from citronellal of the present invention is to carry out oximation and dehydration in one pot, which significantly reduces the process flow compared with the two-step reaction process in the prior art. Citronellal nitrile can be conveniently prepared by controlling the room temperature to 50° C. and stirring the reaction for 0.5 to 4 hours, and then heating to 60 to 100° C. and keeping the temperature for 0.5 to 1 hour, thereby significantly improving the production efficiency compared with the method in the prior art.

[0019] (2) The method of the present invention uses hydroxylamine hydrochloride as the oximation reagent, which has a wide source, low price, is easy to operate, and has low equipment requirements. Compared with the O-trifluoromethylbenzoylhydroxylamine used in the prior art, the price is significantly lower, which is conducive to industrial production.

[0020] (3) The present invention uses the sulfoxide reagent 4-(2-(2-(methylsulfoxide)ethyl)-4-nitrobenzene)morpholine instead of dimethyl sulfoxide, and does not produce the odorous substance of dimethyl sulfide after the reaction, has excellent catalytic reaction efficiency, and the sulfoxide reagent of the present invention can be recycled by a simple method, which meets the requirements of green chemistry and safe production and further reduces costs.

[0021] (4) The yield of citronellal nitrile prepared by the method of the present invention can reach up to 96% or more. DETAILED DESCRIPTION

[0022] The present invention is further described in detail below in conjunction with specific examples. In the following text, unless otherwise specified, the reagents used are purchased through conventional commercial channels in the art and are not further purified or treated with water. The sulfoxide reagent 4-(2-(2-(methylsulfoxide)ethyl)-4-nitrobenzene)morpholine of the present invention is prepared according to the method of patent CN105585540A, which is hereby introduced into this document.

[0023] Example 1

[0024] Citronellal (1.55 g, 10 mmol), hydroxylamine hydrochloride (1.39 g, 20 mmol), 4-(2-(2-(methylsulfoxide)ethyl)-4-nitrobenzene)morpholine (0.3 g, 1 mmol), and triethylamine (3.04 g, 30 mmol) were added to ethanol (20 mL) in sequence, and the mixture was stirred at 45° C. for reaction for 2 hours, then heated to 90° C. and kept warm for 0.5 hours. After the reaction was complete, the mixture was cooled to room temperature, water (20 mL) was added to the reaction system, and then 10% hydrochloric acid was added to adjust the pH to 3, and the liquid was extracted with dichloromethane (3*20 mL). The dichloromethane phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to recover the solvent to obtain a residue, and the residue was separated by silica gel column chromatography (n-hexane: ethyl acetate (v / v) = 20:1) to obtain citronellal nitrile 1.46, with a yield of 96.7%.

[0025] The aqueous phase was adjusted to pH=10 with sodium hydroxide solution, extracted with dichloromethane (3*20mL), and the solvent was recovered by distillation under reduced pressure to obtain the sulfide product of the sulfoxide reagent. The sulfide was dissolved in ethanol, and 30% hydrogen peroxide (1.5mmol) was added dropwise under an oxygen atmosphere and stirred at room temperature for 2 hours. After the reaction was complete, it was extracted with dichloromethane, dried over anhydrous sodium sulfate, and the solvent was recovered under reduced pressure to obtain 0.28g of the sulfoxide reagent 4-(2-(2-(methylsulfoxide)ethyl)-4-nitrobenzene)morpholine, which can be used for the next batch reaction.

[0026] Example 2

[0027] Citronellal (1.55 g, 10 mmol), hydroxylamine hydrochloride (1.39 g, 20 mmol), 4-(2-(2-(methylsulfoxide)ethyl)-4-nitrobenzene)morpholine (0.3 g, 1 mmol), and triethylamine (3.04 g mg, 30 mmol) were added to ethanol (20 mL) in sequence, and the mixture was stirred at 40° C. for reaction for 3 hours, then heated to 80° C. and kept warm for 0.5 hour. After the reaction was complete, the mixture was cooled to room temperature, water (20 mL) was added to the reaction system, and then 10% hydrochloric acid was added to adjust the pH to 3, and the liquid was extracted with dichloromethane (3*20 mL). The dichloromethane phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a residue, and the residue was separated by silica gel column chromatography (n-hexane: ethyl acetate (v / v) = 20:1) to obtain citronellal nitrile 1.44 with a yield of 95.4%.

[0028] The sulfoxide reagent 4-(2-(2-(methylsulfoxide)ethyl)-4-nitrobenzene)morpholine was recovered according to the same method as in Example 1.

[0029] Example 3

[0030] Citronellal (1.55 g, 10 mmol), hydroxylamine hydrochloride (1.39 g, 20 mmol), 4-(2-(2-(methylsulfoxide)ethyl)-4-nitrobenzene)morpholine (0.28 g) recovered according to the method of Example 1, and triethylamine (3.04 g, 30 mmol) were added to ethanol (20 mL) in sequence, and the mixture was stirred at 45° C. for reaction for 2 hours, then heated to 90° C. and kept warm for 0.5 hour. After the reaction was complete, it was cooled to room temperature, water (20 mL) was added to the reaction system, and then 10% hydrochloric acid was added to adjust the pH to 3, and the liquid was extracted with dichloromethane (3*20 mL). The dichloromethane phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to recover the solvent to obtain a residue, and the residue was separated by silica gel column chromatography (n-hexane: ethyl acetate (v / v) = 20:1) to obtain citronellal nitrile 1.41 with a yield of 93.4%.

[0031] The sulfoxide reagent 4-(2-(2-(methylsulfoxide)ethyl)-4-nitrobenzene)morpholine was recovered again according to the same method as in Example 1.

[0032] Example 4

[0033] Citronellal (1.55 g, 10 mmol), hydroxylamine hydrochloride (1.39 g, 20 mmol), 4-(2-(2-(methylsulfoxide)ethyl)-4-nitrobenzene)morpholine (0.3 g, 1 mmol), and pyridine (2.38 g, 30 mmol) were added to ethanol (20 mL) in sequence, and the mixture was stirred at 45° C. for 4 hours, then heated to 90° C. and kept warm for 0.5 hours. After the reaction was complete, it was cooled to room temperature, water (20 mL) was added to the reaction system, and then 10% hydrochloric acid was added to adjust the pH to 3, and the liquid was extracted with dichloromethane (3*20 mL). The dichloromethane phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to recover the solvent to obtain a residue, and the residue was separated by silica gel column chromatography (n-hexane: ethyl acetate (v / v) = 20:1) to obtain citronellal nitrile 1.42 with a yield of 94.0%.

[0034] The sulfoxide reagent 4-(2-(2-(methylsulfoxide)ethyl)-4-nitrobenzene)morpholine was recovered according to the same method as in Example 1.

[0035] Comparative Example 1

[0036] The sulfoxide reagent was replaced by DMSO (0.078 g, 1 mmol), and the remaining operations were the same as in Example 1. The yield of citronellyl nitrile was 44%, and the system after the reaction exhibited an unpleasant odor characteristic of dimethyl sulfide.

[0037] Comparative Example 2

[0038] The solvent and the sulfoxide reagent were replaced with DMSO at the same time, and triethylamine was not added. The remaining operations were the same as in Example 1. The yield of citronellyl nitrile was 52%, and the system after the reaction exhibited an unpleasant odor unique to dimethyl sulfide.

[0039] The above embodiments describe the synthesis method of the present invention and the advantages of the preparation method. Those skilled in the art should understand that the present invention is not limited by the above embodiments. The above embodiments and descriptions are only for illustrating the synthesis method of the present invention. Without departing from the scope of the synthesis method of the present invention, the present invention may have various changes and improvements, and these changes and improvements all fall within the scope of protection of the present invention.

Claims

1. A method for preparing citronellal nitrile from citronellal, characterized in that: The steps include: Citronellal is used as a raw material, hydroxylamine hydrochloride, sulfoxide reagent, organic base and ethanol solvent are added, stirred and reacted at room temperature to 50°C for 0.5 to 4 hours, then heated to 60 to 100°C and kept warm for 0.5 to 1 hour, and citronellal nitrile is obtained by post-treatment. The reaction formula is as follows: Wherein, the sulfoxide reagent is: 4-(2-(2-(methylsulfoxide)ethyl)-4-nitrobenzene)morpholine, and its structural formula is as follows:

2. The method according to claim 1, characterized in that The organic base is any one of trimethylamine, triethylamine, tributylamine and pyridine or a combination of them.

3. The method according to claim 2, characterized in that The organic base is triethylamine.

4. The method according to claim 1 or 2, characterized in that: The feeding molar ratio of citronellal, hydroxylamine hydrochloride, sulfoxide reagent and organic base is 1:1-3:0.01-0.5:2-5.

5. The method according to claim 4, characterized in that The feeding molar ratio of citronellal, hydroxylamine hydrochloride, sulfoxide reagent and organic base is 1:2:0.1:

3.

6. The method according to claim 1 or 2, characterized in that: The reaction temperature of the stirring reaction is 40-50° C., and the reaction time of the stirring reaction is 1 to 3 hours.

7. The method according to claim 6, characterized in that The reaction temperature of the stirring reaction was 45° C., and the reaction time of the stirring reaction was 2 hours.

8. The method according to claim 1 or 2, characterized in that: Raise the temperature to 80-90°C and keep warm for 0.5 hours.

9. The method according to claim 1 or 2, characterized in that: The post-treatment operation is as follows: adding an appropriate amount of water to quench the reaction solution, adding dilute hydrochloric acid to adjust the pH to 2-4, extracting with dichloromethane, drying, concentrating, and separating the organic phase by silica gel column chromatography to obtain citronellal; adding sodium hydroxide to the aqueous phase to adjust the pH to 9-11, extracting with dimethane, and concentrating to obtain the sulfide of the reduction product of the sulfoxide reagent, dissolving the sulfide in ethanol, adding 30% hydrogen peroxide dropwise, stirring at room temperature for 2 hours, and obtaining the sulfoxide reagent 4-(2-(2-(methylsulfoxide)ethyl)-4-nitrobenzene)morpholine, which can be used for the next batch reaction.

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