阅读说明：本技术 一种利用mto催化制备罗汉柏木烷酮的方法 (Method for preparing thujopsis japonica ketonic acid by utilizing MTO catalysis ) 是由 朱凯 张胜 于 2021-11-08 设计创作，主要内容包括：本发明公开了一种利用MTO(甲基三氧化铼)催化制备罗汉柏木烷酮的方法,属于精细有机化学品合成技术领域。该方法在MTO催化剂作用下,以3-甲基吡唑为碱性配体,对罗汉柏木烯进行氧化反应得到罗汉柏木烷酮。本发明使用MTO作为催化剂,具有良好的溶解性和热稳定性且绿色环保；以3-甲基吡唑为碱性配体使得反应中副反应减少,烷酮选择性增加,目标产物得率有很大提高；所制备得到的罗汉柏木烷酮具有甜的木香和龙涎香气息,香气可贵且持久,稳定性高,具有很好的工业化应用前景,可用于香水、皂用、化妆品香精等日用香精中。(The invention discloses a method for preparing thujopsis japonica ketonic acid by utilizing MTO (methyl rhenium trioxide) catalysis, belonging to the technical field of fine organic chemical synthesis. The method takes 3-methylpyrazole as an alkaline ligand to carry out oxidation reaction on thujopsida julian alkene under the action of an MTO catalyst to obtain the thujopsida julian. The invention uses MTO as a catalyst, has good solubility and thermal stability and is green and environment-friendly; 3-methylpyrazole is used as an alkaline ligand, so that side reactions in the reaction are reduced, the selectivity of the alkanone is increased, and the yield of a target product is greatly improved; the prepared thujopsida japonica ketonic ketone has sweet smell of costustoot and ambergris, has noble and lasting fragrance and high stability, has good industrial application prospect, and can be used in daily essences such as perfume, soap, cosmetic essence and the like.)

1. A method for preparing Thujopsis dolabrata ketonic acid by utilizing MTO catalysis is characterized in that: under the action of an MTO catalyst, 3-methylpyrazole is taken as an alkaline ligand to carry out oxidation reaction on thujopsis amurensis alkene to obtain the thujopsis amurensis ketone.

2. The method for preparing thujopsida alkanone using MTO catalysis as claimed in claim 1, wherein: adding thujopsis juveniles, MTO, 3-methylpyrazole and organic solvent into a reactor, stirring at controlled temperature, and slowly dropwise adding 30% H₂O₂Carrying out reaction; after the reaction is finished, cooling to room temperature, extracting to obtain an organic phase, washing to be neutral, distilling to recover the solvent, and then carrying out reduced pressure rectification to obtain the product of the cedarwood keton.

3. The method for preparing thujopsida alkanone using MTO catalysis as claimed in claim 1 or 2, wherein the organic solvent is selected from ethanol, dichloromethane, 1, 2-dichloroethane, ethyl acetate.

4. The method for preparing thujopsida alkanone using MTO catalysis as claimed in claim 1 or 2, wherein the thujopsida alkene and 30% H₂O₂The molar ratio of (A) to (1-5).

5. The method for preparing thujopsida japonica thunb by catalysis of MTO according to claim 1 or 2, wherein the mass ratio of thujopsida japonica thunb to MTO is 1: 0.1-0.5%.

6. The method for preparing thujopsida alkanone using MTO catalysis as claimed in claim 1 or 2, wherein the mass ratio of thujopside to 3-methylpyrazole is 1: (6-10%).

7. The method for preparing thujopsida pine alkanone using MTO catalysis as claimed in claim 1 or 2, wherein the temperature is controlled to be 20-40 ℃ and the reaction time is 2-4 h.

8. The method for preparing Thujopsis dolabrata through catalysis of MTO as claimed in claim 2, wherein the extraction is performed with ethyl acetate, the organic phase is separated, and 10% Na is sequentially used₂CO₃Washing the solution, distilled water and saturated NaCl solution to neutrality, distilling to recover solvent, and final vacuum rectification to obtain the product.

Technical Field

The invention belongs to the technical field of fine organic chemical synthesis, and particularly relates to a method for preparing thujopsis japonica ketonic acid by utilizing catalysis of MTO (methyl rhenium trioxide).

Background

The Thujopsis dolabrata ketonic is a sesquiterpene ketone compound, is colorless to light yellow oily liquid, has sweet smell of radix aucklandiae and ambergris, has noble and lasting fragrance, and can be used for preparing wood-fragrance type and ambergris-fragrance type daily essences, as well as perfume, leather and tobacco.

At present, cedrane ketone spices are mainly synthesized by oxidizing alpha, beta-cedrene serving as a raw material, and the obtained cedrane ketone product has a pungent smell, an unobvious animal fragrance and a common quality; the thujopsida japonica ketone synthesized by using thujopsida japonica alkene as a raw material has strong fragrance and has the characteristic of noble fragrance of musk and ambergris. Both thujopsirene and α, β -cedrene are derived from cedarwood oil, but α, β -cedrene has been studied more in the synthesis of high-end cedar-based fragrances, and thujopsirene has not been well utilized.

Foreign researches report that the thujopsis japonica alkene is oxidized to synthesize the thujopsis japonica ketone, but the method mainly adopts a synthetic route which takes organic peroxy acid as an oxidizing agent, and has the problems of low product yield and environmental pollution due to unstable property and strong corrosivity of the organic peroxy acid, so that the use is limited. In earlier research results CN111499502A of the present applicant, a method for synthesizing thujopsilon is disclosed, which mainly comprises the following steps: phosphotungstic acid and hexadecyl trimethyl ammonium chloride are used as raw materials to prepare phosphotungstic acid quaternary ammonium salt, and the phosphotungstic acid quaternary ammonium salt is loaded on active carbon to prepare an active carbon loaded phosphotungstic acid quaternary ammonium salt catalyst; carrying out oxidation reaction on thujopsis japonica alkene under the action of an activated carbon loaded phosphotungstic acid quaternary ammonium salt catalyst to obtain thujopsis japonica ketonic acid; the method uses the activated carbon-loaded quaternary ammonium phosphotungstate as the catalyst, can improve the stability of the catalyst, is convenient for regeneration and recycling of the catalyst, reduces the discharge of waste materials, is beneficial to the environment, has simple synthesis method, small corrosivity to equipment, is safe and environment-friendly, and has low cost. The method can effectively solve the problems of the existing foreign preparation process of the cedarwood ketonic acid, the obtained product has high purity, the transformation rate of the cedarwood alkene is higher, but the yield of the cedarwood ketonic acid product in the method still has a space for improving, so that the synthesis method of the high yield of the cedarwood ketonic acid is further developed, and the method has important research value and industrial application prospect.

Disclosure of Invention

Aiming at the problems in the prior art, the technical problem to be solved by the invention is to provide a method for preparing the cedarwood ketone by utilizing MTO catalysis, and the method further improves the yield of the target product cedarwood ketone on the basis of ensuring the product purity and the raw material conversion rate.

In order to solve the technical problems, the technical scheme adopted by the invention is as follows:

a method for preparing Thujopsis dolabrata ketonic acid by MTO catalysis comprises the following steps: under the action of an MTO catalyst, 3-methylpyrazole is taken as an alkaline ligand to carry out oxidation reaction on thujopsis amurensis alkene to obtain the thujopsis amurensis ketone.

The method for preparing the thujopsis japonica ketonic acid by utilizing MTO catalysis specifically comprises the following steps: adding thujopsis juveniles, MTO, 3-methylpyrazole and organic solvent into a reactor, stirring at controlled temperature, and slowly dropwise adding 30% H₂O₂Carrying out reaction; after the reaction is finished, cooling to room temperature, extracting to obtain an organic phase, washing to be neutral, distilling to recover the solvent, and then carrying out reduced pressure rectification to obtain a crude product of the thujopsis dolabrata. And (4) carrying out column chromatography on the crude product to obtain the high-purity thujopsis japonica ketonic acid, and characterizing by GC-MS.

The organic solvent is selected from ethanol, dichloromethane, 1, 2-dichloroethane and ethyl acetate.

Said thujopsirene and 30% H₂O₂The molar ratio of (A) to (1-5).

The mass ratio of the thujopsilene to the MTO is 1: 0.1-0.5%.

The mass ratio of the thujopsilene to the 3-methylpyrazole is 1: 6-10%.

The temperature is controlled to be 20-40 ℃, and the reaction time is 2-4 h.

The catalytic preparation by utilizing MTOMethod for preparing Thujopsis dolabrata ketone comprises extracting with ethyl acetate, separating organic phase, sequentially extracting with 10% Na₂CO₃Washing the solution, distilled water and saturated NaCl solution to neutrality, distilling to recover solvent, and vacuum rectifying to obtain coarse product of Luohansu xylon. And (3) carrying out column chromatography on the crude product to obtain the high-purity thujopsida japonica thunb, wherein the purified product is not used for calculating the product yield, but used for carrying out characterization by GC-MS and nuclear magnetic resonance.

According to the method, methyl rhenium trioxide is used as a catalyst, but the catalytic system has the defect that glycol and other products are easily generated, so that the acidity of rhenium atoms at the center of MTO is reduced by adding a basic ligand 3-methylpyrazole, and the selectivity and yield of the Thujopsis dolabrata ketonic acid in the reaction are improved.

Has the advantages that: compared with the prior art, the invention has the advantages that:

1) according to the invention, methyl rhenium trioxide is used as a catalyst, so that the catalyst has excellent catalytic performance, good solubility and thermal stability, 3-methylpyrazole is used as an alkaline ligand, so that side reactions in the reaction are reduced, the selectivity of the alkanone is increased, and the yield is greatly improved.

2) The Thujopsis dolabrata ketonic acid has sweet smell of costustoot and ambergris, the fragrance is noble, the fragrance-retaining time is long, and the stability is high;

3) the preparation method disclosed by the invention is simple in preparation flow, short in reaction time, green and environment-friendly, and has a good industrial application prospect.

Drawings

FIG. 1 is a mass spectrum of synthesized Thujopsis dolabrata ketonic acid.

Detailed Description

The invention is further described with reference to specific examples. The cedrene used as a raw material in the following examples and comparative examples had a cedrene content of 68%; the correlation result calculation formula is as follows:

and (3) calculating yield: yield (%) ═ product amount (g) product content/theoretical product amount (g);

theoretical product amount (g) ═ raw material amount (g) · raw material content · molecular weight of thujopside ketonic acid/molecular weight of thujopside alkene;

conversion (%) — product amount (g) — (1-product content)/raw material amount (g) — raw material content;

example 1

6.12g of thujopsilene (content 68%), 0.018g of methyltrioxorhenium, 0.612g of 3-methylpyrazole, 15mL of ethanol were taken and added to the reactor, and 6.8g of 30% H₂O₂Slowly dropped into the reactor, and then stirred at 30 ℃ for 3 hours. After the reaction was completed, the reaction solution was extracted with ethyl acetate (3 × 50 mL); the organic phase was successively treated with 10% Na₂CO₃Washing with a solution (3 × 50mL), deionized water (3 × 50mL), and a saturated sodium chloride solution (3 × 50 mL); removing water from the organic phase by using anhydrous sodium sulfate, distilling to recover the solvent, and then carrying out vacuum rectification to obtain 3.14g of a crude product of the Thujopsis dolabrata wood ketone, wherein the content of the Thujopsis dolabrata wood ketone is 81.9% by gas chromatography analysis, and the calculation shows that the yield of the Thujopsis dolabrata wood ketone is 57.3% and the conversion rate of the Thujopsis dolabrata wood alkene is 76.8%; and carrying out column chromatography on the crude product to obtain the cedarwood keton with the purity of 94.6 percent, and determining the cedarwood keton as the cedarwood keton by GC-MS characterization.

Example 2

6.12g of thujopsilene (content 68%), 0.018g of methyltrioxorhenium, 0.612g of 3-methylpyrazole, 15mL of dichloromethane were taken, added to the reactor, and 6.8g of 30% H₂O₂Slowly dropped into the reactor, and then stirred at 30 ℃ for 3 hours. After the reaction was completed, the reaction solution was extracted with ethyl acetate (3 × 50 mL); the organic phase was successively treated with 10% Na₂CO₃Washing with a solution (3 × 50mL), deionized water (3 × 50mL), and a saturated sodium chloride solution (3 × 50 mL); removing water from the organic phase by using anhydrous sodium sulfate, distilling to recover the solvent, and then carrying out vacuum rectification to obtain 3.53g of a crude product of the Thujopsis dolabrata wood ketone, wherein the content of the Thujopsis dolabrata wood ketone is 76.8% by gas chromatography analysis, and the obtained product is calculated to obtain that the yield of the Thujopsis dolabrata wood ketone is 60.4% and the conversion rate of the Thujopsis dolabrata wood alkene is 80.7%; and performing column chromatography on the crude product to obtain the cedarwood keton with the purity of 93.7 percent, and determining the cedarwood keton by GC-MS characterization.

Example 3

Taking 6.12g of thujopside (content 68%), 0.018g of methyl rhenium trioxide, 0.612g of 3-methylpyrazole and 15mL Ethyl acetate, charged to the reactor, and 6.8g of 30% H₂O₂Slowly dropped into the reactor, and then stirred at 30 ℃ for 3 hours. After the reaction was completed, the reaction solution was extracted with ethyl acetate (3 × 50 mL); the organic phase was successively treated with 10% Na₂CO₃Washing with a solution (3 × 50mL), deionized water (3 × 50mL), and a saturated sodium chloride solution (3 × 50 mL); removing water from the organic phase by using anhydrous sodium sulfate, distilling to recover the solvent, and then carrying out vacuum rectification to obtain 3.84g of a crude product of the Thujopsis dolabrata wood ketone, wherein the content of the Thujopsis dolabrata wood ketone is 73.2% by gas chromatography analysis, and the obtained product is calculated to obtain that the yield of the Thujopsis dolabrata wood ketone is 62.6% and the conversion rate of the Thujopsis dolabrata wood alkene is 81.3%; and carrying out column chromatography on the crude product to obtain the cedarwood keton with the purity of 94.1%, and determining the cedarwood keton by GC-MS characterization.

Example 4

6.12g of thujopsilene (content 68%), 0.018g of methyltrioxorhenium, 0.612g of 3-methylpyrazole, 15mL of 1, 2-dichloroethane were charged in a reactor, and 6.8g of 30% H₂O₂Slowly dropped into the reactor, and then stirred at 30 ℃ for 3 hours. After the reaction was completed, the reaction solution was extracted with ethyl acetate (3 × 50 mL); the organic phase was successively treated with 10% Na₂CO₃Washing with a solution (3 × 50mL), deionized water (3 × 50mL), and a saturated sodium chloride solution (3 × 50 mL); removing water from the organic phase by using anhydrous sodium sulfate, distilling to recover the solvent, and then carrying out vacuum rectification to obtain 5.16g of a crude product of the Thujopsis dolabrata wood ketone, wherein the content of the Thujopsis dolabrata wood ketone is 62.9% by gas chromatography analysis, and the calculation shows that the yield of the Thujopsis dolabrata wood ketone is 72.3% and the conversion rate of the Thujopsis dolabrata wood alkene is 96.7%; and carrying out column chromatography on the crude product to obtain the cedarwood keton with the purity of 94.8%, and determining the cedarwood keton by GC-MS characterization.

Example 5

6.12g of thujopsilene (content 68%), 0.018g of methyltrioxorhenium, 0.612g of 3-methylpyrazole, 15mL of 1, 2-dichloroethane were charged in a reactor, and 6.8g of 30% H₂O₂Slowly dropped into the reactor, and then stirred at 30 ℃ for 2 h. After the reaction was completed, the reaction solution was extracted with ethyl acetate (3 × 50 mL); the organic phase was successively treated with 10% Na₂CO₃Solution (3 × 50mL), deionizationWashing with brine (3 × 50mL) and saturated sodium chloride solution (3 × 50 mL); removing water from the organic phase by using anhydrous sodium sulfate, distilling to recover the solvent, and then carrying out vacuum rectification to obtain 4.36g of a crude product of the Thujopsis dolabrata wood ketone, wherein the content of the Thujopsis dolabrata wood ketone is 67.1% by gas chromatography analysis, and the calculation shows that the yield of the Thujopsis dolabrata wood ketone is 65.2% and the conversion rate of the Thujopsis dolabrata wood alkene is 89.1%; and performing column chromatography on the crude product to obtain the cedarwood keton with the purity of 93.2 percent, and determining the cedarwood keton by GC-MS characterization.

Example 6

6.12g of thujopsilene (content 68%), 0.018g of methyltrioxorhenium, 0.612g of 3-methylpyrazole, 15mL of 1, 2-dichloroethane were charged in a reactor, and 6.8g of 30% H₂O₂Slowly dropped into the reactor, and then stirred at 30 ℃ for 4 h. After the reaction was completed, the reaction solution was extracted with ethyl acetate (3 × 50 mL); the organic phase was successively treated with 10% Na₂CO₃Washing with a solution (3 × 50mL), deionized water (3 × 50mL), and a saturated sodium chloride solution (3 × 50 mL); removing water from the organic phase by using anhydrous sodium sulfate, distilling to recover the solvent, and then carrying out vacuum rectification to obtain 5.07g of a crude product of the Thujopsis dolabrata wood ketone, wherein the content of the Thujopsis dolabrata wood ketone is 64.3% by gas chromatography analysis, and the obtained product is calculated to obtain that the yield of the Thujopsis dolabrata wood ketone is 71.6% and the conversion rate of the Thujopsis dolabrata wood alkene is 96.9%; and carrying out column chromatography on the crude product to obtain the hinokitione with the purity of 92.6 percent, and determining the hinokitione by GC-MS characterization.

The product of the thujopsidone synthesized in the above examples was characterized by gas chromatography-mass spectrometry (GC-MS): 220[ M ] M/z]⁺As shown in FIG. 1, the molecular ion peak is 220, and C₁₅H₂₄O completely conforms, and the major fragments m/z are: 220. 192, 178, 163, 149, 137, 123, 107, 95, 81, 67, 55, 41; the molecular structural formula is as follows:

comparative example 1

Synthesis of Thujopsis dolabrata ketonic acid: taking 5g of thujoram (the content of 68 percent),0.4g of 20% activated carbon-supported quaternary ammonium phosphotungstate catalyst, and 5mL of 30% H₂O₂And 15mL of acetone were added to the reactor and stirred at 60 ℃ for 6 h. After the reaction was completed, the reaction solution was extracted with ethyl acetate (3 × 50 mL); the organic phase was washed successively with deionized water (3 × 50mL), saturated sodium chloride solution (3 × 50 mL); removing water from the organic phase by using anhydrous sodium sulfate, then carrying out reduced pressure distillation, and then carrying out reduced pressure rectification to obtain 4.1g of a crude product of the Thujopsis dolabrata wood ketone, wherein the content of the Thujopsis dolabrata wood ketone is 42.8% by gas chromatography analysis, and the obtained product is obtained by calculation, wherein the yield of the Thujopsis dolabrata wood ketone is 47.9%, and the conversion rate of the Thujopsis dolabrata wood alkene is 68.1%. The crude product was subjected to column chromatography to obtain the desired product, i.e., hinokitione, with a purity of 94.6%.

Comparative example 2

Synthesis of Thujopsis dolabrata ketonic acid: 5g of thujopsis juvenine (content: 68%), 0.4g of 30% activated carbon-supported quaternary ammonium phosphotungstate catalyst, 5mL of 30% H2O2 and 15mL of ethyl acetate were added to a reactor, and stirred at 60 ℃ for 6H. After the reaction was completed, the reaction solution was extracted with ethyl acetate (3 × 50 mL); the organic phase was washed successively with deionized water (3 × 50mL), saturated sodium chloride solution (3 × 50 mL); removing water from the organic phase by using anhydrous sodium sulfate, then carrying out reduced pressure distillation, and then carrying out reduced pressure rectification to obtain 4.8g of a crude product of the Thujopsis dolabrata wood ketone, wherein the content of the Thujopsis dolabrata wood ketone is 65.7% by gas chromatography analysis, the crude product is obtained by calculation, the yield of the Thujopsis dolabrata wood ketone is 65.7%, the conversion rate of the Thujopsis dolabrata wood alkene is 90.9%, and the crude product is subjected to column chromatography to obtain the Thujopsis dolabrata wood ketone with the purity of 95.7%.

Comparative example 3

Synthesis of Thujopsis dolabrata ketonic acid: 5g of thujopsilon (content: 68%), 0.4g of 40% activated carbon supported quaternary ammonium phosphotungstate catalyst, 5mL of 30% H2O2 and 15mL of dichloromethane were added to a reactor, and stirred at 60 ℃ for 6H. After the reaction was completed, the reaction solution was extracted with ethyl acetate (3 × 50 mL); the organic phase was washed successively with deionized water (3 × 50mL), saturated sodium chloride solution (3 × 50 mL); removing water from the organic phase by using anhydrous sodium sulfate, then carrying out reduced pressure distillation, and then carrying out reduced pressure rectification to obtain 4.6g of a crude product of the Thujopsis dolabrata wood ketone, wherein the content of the Thujopsis dolabrata wood ketone is 48.0% by gas chromatography analysis, the crude product is obtained by calculation, the yield of the Thujopsis dolabrata wood ketone is 60.2%, the conversion rate of the Thujopsis dolabrata wood alkene is 85.6%, and the crude product is subjected to column chromatography to obtain the Thujopsis dolabrata wood ketone with the purity of 95.1%.

Comparative example 4

Synthesis of Thujopsis dolabrata ketonic acid: 5g of thujopsis juvenine (content: 68%), 0.4g of 50% activated carbon-supported quaternary ammonium phosphotungstate catalyst, 5mL of 30% H2O2 and 15mL of ethyl acetate were added to a reactor, and stirred at 60 ℃ for 6H. After the reaction was completed, the reaction solution was extracted with ethyl acetate (3 × 50 mL); the organic phase was washed successively with deionized water (3 × 50mL), saturated sodium chloride solution (3 × 50 mL); removing water from the organic phase by using anhydrous sodium sulfate, then carrying out reduced pressure distillation, and then carrying out reduced pressure rectification to obtain 4.5g of a crude product of the Thujopsis dolabrata wood ketone, wherein the content of the Thujopsis dolabrata wood ketone is 46.6% by gas chromatography analysis, the crude product is obtained by calculation, the yield of the Thujopsis dolabrata wood ketone is 57.2%, the conversion rate of the Thujopsis dolabrata wood alkene is 81.7%, and the crude product is subjected to column chromatography to obtain the Thujopsis dolabrata wood ketone with the purity of 94.3%.

The above description is only of the preferred embodiments of the present invention, and it should be noted that: it will be apparent to those skilled in the art that various modifications can be made without departing from the principles of the invention and these modifications are to be considered within the scope of the invention.