WO2017124676A1

WO2017124676A1 - Method for synthesizing carvacrol by using limo nene epoxides

Info

Publication number: WO2017124676A1
Application number: PCT/CN2016/084009
Authority: WO
Inventors: 刘晓涛; 李绍玉; 吴庆典; 万猛; 张建洋; 刘颖; 汤海潮
Original assignee: 淮安万邦香料工业有限公司
Priority date: 2016-01-22
Filing date: 2016-05-31
Publication date: 2017-07-27
Also published as: CN105481657A; CN105481657B

Abstract

The present invention provides a method for synthesizing carvacrol by using limo nene epoxides. The method comprises the following steps: step 1, under the action of a Lewis acid catalyst A, heating limo nene epoxide for open-loop rearrangement reaction to produce isodihydrocarvone, after reaction, adding white oil into the reaction liquid, conducting vacuum distillation to obtain an isodihydrocarvone end product, and leaving the catalyst A in the residue; step 2, dissolving isodihydrocarvone prepared in the step 1 and a catalyst B into a solvent, heating the solvent for dehydrogenation oxidation to produce carvacrol, monitoring the reaction process by using gas chromatography, when the content of isodihydrocarvone is 30% to 40%, terminating the reaction, filtering and separating out the catalyst B, conducting reduced-pressure distillation on the filtrate, reclaiming isodihydrocarvone and the solvent that are not subjected to reaction, and further, conducting distillation to obtain a carvacrol end product. The raw material in the present invention is low in price and easily accessible, the synthesis process is environmentally-friendly, the catalysts can be recycled, and the method is suitable for industrial production.

Description

Method for synthesizing carvacrol with epoxy limonene

Technical field

The invention belongs to the technical field of chemical industry, and relates to a chemical synthesis method, in particular to a method for synthesizing carvacrol with epoxy limonene.

technical background

Carvacrol is a colorless to pale yellow thick oily liquid with thymol phenolic properties. It is a commonly used food additive and fragrance. It has low toxicity and natural characteristics and is approved for safety in the US and Europe. Food additive. Natural carvacrol is mainly found in a variety of Labiatae plants, such as thyme, oregano and the like. Carvacrol has a wide range of functions and applications. It destroys and changes the cell membrane structure of the pathogenic bacteria, or the structure of the mycelium, or effectively inhibits the activity of the conidia, and has good growth inhibition effects on bacteria, yeasts, fungi, insects and mites. Good antibacterial and insecticidal effects. It is an active ingredient of thyme activating blood and removing phlegm, and achieves platelet activation by mediating the anti-thrombotic signal transduction pathway of G13 protein-coupled hoA/Rho-kinase. These effects make it widely used as a natural antibacterial preservative in food, pharmaceuticals, cosmetics and other products.

At present, there are two main methods for the synthesis of carvacrol: one is to use carvone as a raw material, and aromatization to form carvacrol under the action of a strong acid or a metal catalyst. For example, CN101475448A reports the use of organic or inorganic acids as the main catalyst, PEG-400 or PEG-600 as a cocatalyst to promote the intramolecular rearrangement of carvone to form carvacrol; Linstead, RP reported that metal palladium catalyzes carvone The reaction of dehydroisomerization to synthesize carvacrol (Journal of the Chemical Society, 1940, 1139-1147). The advantages of this type of method are good reaction selectivity and high yield, but the raw carvone as a perfume product is expensive. The cost advantage of the process is greatly reduced. Second, the ino-methylphenol is used as a raw material to synthesize carvacrol by a Friedel-Craft reaction with isopropanol or 2-halopropane. For example, a method for synthesizing carvacrol by reacting o-methylphenol with 2-chloropropane with aluminum trichloride or ferric chloride is reported in the patent CN 1488615, but the method has a large amount of solid waste of aluminum salt and iron salt. , causing environmental pollution, limiting its further application in production.

Summary of the invention

In view of the deficiencies of the prior art, the present invention provides a method of synthesizing carvacrol with epoxy limonene.

The invention is achieved by the following technical solutions:

A method for synthesizing carvacrol with epoxy limonene comprises the following steps:

In the first step, the epoxy limonene is subjected to a ring-opening rearrangement reaction under the action of the Lewis acid catalyst A to form iso-dihydrocarvone. The reaction is monitored by gas chromatography, the raw material disappears, and the reaction is finished. Adding white oil to the reaction liquid, vacuum distillation to obtain a finished product of iso-dihydrocarvone, and catalyst A remaining in the liquid;

In the second step, the iso-dihydrocarvone and the catalyst B prepared in the first step are dissolved in a solvent, and dehydro-oxidation reaction is generated by heating to form carvacrol, and the content of the iso-dihydrocarvone is monitored by gas chromatography during the reaction. When the remaining 30%-40%, the reaction was terminated, the catalyst B was separated by filtration, and the filtrate was subjected to vacuum distillation, and the unreacted iso-dihydrocarvone and the solvent were recovered, and further distillation was carried out to obtain a carvacrol finished product.

The chemical reaction equation is as follows:

A further improvement of the invention is:

The first step does not require a solvent, and the Lewis acid catalyst A includes a metallic iron of a weak Lewis acid. Nickel, zinc, palladium, copper, ruthenium, platinum sulfate, halide and acetate; or strong Lewis acid metal zinc, copper trifluoroacetate, trifluoromethanesulfonate, etc.; epoxy limonene The molar ratio to the catalyst A is 100:1 to 5; when the catalyst A is a weak Lewis acid, the reaction temperature is 140 ° C to 170 ° C, the reaction time is 2 to 8 h; when the catalyst A is a strong Lewis acid, the reaction is carried out at room temperature. The reaction time is 1 to 5 hours; after the rectification, the kettle liquid containing the catalyst A is recycled at least once, and the catalytic activity is not weakened.

In the second step, the solvent is an inert substance capable of azeotroping with water, including toluene, fluorobenzene, anisole, xylene, and the amount thereof is adjusted according to the temperature required for the reaction; the carbon-based composite catalyst B is copper supported on carbon. a catalyst on a dielectric material, wherein the content of copper is 3 wt%; the molar ratio of isodihydrocarvone to catalyst B is 100:1 to 15; the reaction temperature is 190 to 230 ° C, and the time is 4 to 10 h; Catalyst B was recycled at least once and the catalytic activity was not attenuated.

A still further development of the invention is:

In the second step, the dehydrogenation reaction slows down and the by-products increase, so the selectivity is best when the remaining raw materials are close to 30-40%, and the reaction can be stopped at this time; the pump is continuously applied to the reaction liquid during the reaction. The drum air continuously distills off the water produced by the dehydrogenation to promote the conversion of the reaction, and the air or oxygen atmosphere is more favorable for the reaction.

The beneficial effects of the invention are:

1,2-epoxy limonene is an important organic chemical intermediate, and its molecular structure has a very active epoxy group, which undergoes self-rearrangement in the molecule or ring-opening reaction with various nucleophiles. A series of important organic compounds for use in medicine, pesticides, coatings, resins, surfactants, etc. Moreover, 1,2-epoxy limonene can be directly produced by epoxidation of limonene, which has the advantages of convenient source and low cost. Moreover, the synthetic process of the invention is green and environmentally friendly, and the catalyst can be recycled, which is suitable for industrial production.

detailed description

Embodiment 1:

Step 1 In a 500 mL three-necked flask, 300 g (2 mol) of epoxy limonene and 5 g (0.03 mol) of cuprous bromide were added, and then reacted at 160 ° C for 6 to 8 hours. After GC showed that the reaction was completed, 30 g of white oil was added to the reaction. After distillation under reduced pressure, 250 g of iso-dihydrocarvone was obtained in an amount of more than 90%, and the yield was 83%. Further, the rectification tank containing the catalyst can again catalyze the reaction to proceed normally.

Step 2: 250 g (1.67 mol) of isohydrohydrocarvone and 20 g of xylene obtained above were placed in a 500 mL three-necked flask, and then 100 g (0.05 mol) of catalyst B was added, and the reaction was carried out under reflux at 190 to 220 ° C. The pump continuously blows air into the surface of the reaction liquid to continuously distill off the water produced by the dehydrogenation. About 4 to 5 hours, the GC shows that 39% of the isohydrohydrocarvone remains, the reaction is stopped, the catalyst is removed by filtration, and the filtrate is decompressed. The distillation was carried out, and 15 g of a solvent and 95 g of a raw material which did not react were recovered, and further rectification was carried out to obtain 120 g of a carvacrol finished product having a content of more than 98%, and an effective yield was 77%. The catalyst B obtained by filtration can be reused.

Note: Reaction step 2 "Efficient Yield" is calculated based on the amount of iso-dihydrocarvone involved in the reaction (net of recovery).

Embodiment 2:

Step 1 In a 500 mL three-necked flask, 300 g (2 mol) of epoxy limonene and 3 g (0.02 mol) of cuprous bromide were added, and then reacted at 170 ° C for about 4 to 5 hours. After GC showed that the reaction was completed, the content obtained by vacuum distillation was greater than that. 90% iso-dihydrocarvone 255g, yield 85%.

Step 2: 255 g (1.7 mol) of isohydrohydrocarvone obtained above and 20 g of xylene were placed in a 500 mL three-necked flask, and then 50 g (0.023 mol) of catalyst B was added, and the reaction was carried out under reflux at 190 to 220 ° C. The pump is continuously blown into the surface of the reaction liquid for about 6 to 8 hours. The GC shows 40% of the remaining isohydrohydrocarvone. The reaction is stopped, the catalyst is removed by filtration, and the filtrate is subjected to vacuum distillation to recover 16 g of the solvent and no reaction. The raw material of 97 g was further rectified to obtain 118 g of the finished carvacrol having a content of more than 98%, and the effective yield was 75%.

Embodiment 3:

Step 1 In a 500 mL three-necked flask, 300 g (2 mol) of epoxy limonene and 3.5 g (0.01 mol) of nickel trifluoromethanesulfonate were added, and then reacted at 160 ° C for about 2 to 3 hours. After GC showed that the reaction was completed, the vacuum distillation was carried out. 240 g of iso-dihydrocarvone was obtained in an amount of more than 90%, and the yield was 80%.

Step 2: 240 g (1.6 mol) of isohydrohydrocarvone and 20 g of xylene obtained above were placed in a 500 mL three-necked flask, and then 80 g (0.038 mol) of catalyst B was added, and the reaction was carried out under reflux at 190 to 220 ° C. The pump is continuously blown into the surface of the reaction liquid for about 6 to 7 hours. The GC shows the remaining 32% of iso-dihydrocarvone. The reaction is stopped, the catalyst is removed by filtration, and the filtrate is subjected to vacuum distillation to recover 16 g of the solvent and no reaction. 76 g of the raw material was further rectified to obtain 118 g of the finished carvacrol having a content of more than 98%, and the effective yield was 72%.

Embodiment 4:

Step 1 In a 500 mL three-necked flask, 300 g (2 mol) of epoxy limonene and 3 g (0.008 mol) of copper triflate were added, and the mixture was reacted at room temperature for about 3 to 5 hours. After GC showed that the reaction was completed, distillation under reduced pressure was obtained. The content of iso-dihydrocarvone 235g is more than 90%, and the yield is 78%.

Step 2: 235 g (1.56 mol) of isohydrohydrocarvone and 20 g of chlorobenzene obtained above were put into a 500 mL three-necked flask, and then 100 g (0.05 mol) of catalyst B was added, and the reaction was carried out under reflux at 190-220 ° C. The pump is continuously blown into the surface of the reaction liquid for about 5 to 6 hours. The GC shows the remaining 38% of iso-dihydrocarvone. The reaction is stopped, the catalyst is removed by filtration, the filtrate is subjected to vacuum distillation, and 17 g of the solvent is recovered. 96 g of the raw material was further subjected to rectification to obtain 113 g of a carvacrol product having a content of more than 98%, and the effective yield was 76%.

Claims

A method for synthesizing carvacrol with epoxy limonene, which comprises the steps of:

In the first step, the epoxy limonene is heated under the action of the Lewis acid catalyst A to undergo ring-opening rearrangement reaction to form iso-dihydrocarvone. After the reaction is completed, white oil is added to the reaction liquid, and the distillation is carried out under reduced pressure. Dihydrocarvone;

In the second step, the iso-dihydrocarvone and the carbon-based composite catalyst B prepared in the first step are dissolved in a solvent, and dehydrogenation reaction is generated by heating to form carvacrol, and the catalyst B is separated by filtration, and the filtrate is subjected to vacuum distillation to obtain parsley. Phenol finished product.
A method for synthesizing carvacrol from epoxy limonene according to claim 1, wherein the chemical reaction equation is as follows:
A method for synthesizing carvacrol from epoxy limonene according to claim 1, wherein:

In the first step, the Lewis acid catalyst A is a metal, iron, nickel, zinc, palladium, copper, ruthenium, platinum sulfate, a halide and an acetate of a weak Lewis acid; or a strong Lewis acid metal zinc, Copper trifluoroacetate, trifluoromethanesulfonate, and the like.

In the second step, the carbon-based composite catalyst B is a catalyst in which copper is supported on a carbon medium material, wherein the content of copper is 3 wt%.
A method for synthesizing carvacrol from epoxy limonene according to claim 3, wherein:

In the first step, when the catalyst A is a weak Lewis acid, the reaction temperature is 140 ° C ~ 170 ° C; when the catalyst A is a strong Lewis acid, the reaction temperature is 20 ° C ~ 35 ° C;

In the second step, the reaction temperature is 190 to 230 °C.
A method for synthesizing carvacrol from epoxy limonene according to claim 1, wherein:

The reaction process of the first step does not require a solvent;

The reaction process of the second step requires adding a small amount of a solvent which azeotropes with water, including toluene, fluorobenzene, anisole or xylene.
A method for synthesizing carvacrol from epoxy limonene according to claim 1, wherein:

In the first step, the molar ratio of epoxy limonene to catalyst A is 100:1 to 5;

In the second step, the molar ratio of iso-dihydrocarvone to the catalyst B (Cu: 3 wt%) is 100:1 to 15.
A method for synthesizing carvacrol from epoxy limonene according to claim 1, wherein:

In the first step, the kettle liquid containing the catalyst A is recycled at least once;

In the second step, the catalyst B obtained by filtration is recycled at least once.
A method for synthesizing carvacrol from epoxy limonene according to claim 1, wherein the water produced by dehydrogenation is continuously distilled off during the second step of the reaction.
The method for synthesizing carvacrol from epoxy limonene according to claim 1, wherein the step two is monitored by gas chromatography, and the iso-dihydrocarvone content is 30%-40. The reaction is terminated at % and the reaction is continued to cause a significant decrease in selectivity.