CN-122010682-A - Method for synthesizing hydrated carvacrol by using 2, 3-epoxy pinane

Abstract

The invention belongs to the technical field of organic synthesis, and particularly discloses a method for synthesizing hydrated carvacrol by using 2, 3-epoxy pinane, which comprises the following steps of taking 2, 3-epoxy pinane as a raw material, taking organic phosphoric acid as a catalyst in a solvent, taking a microchannel reactor as reaction equipment, adding deionized water to enable the 2, 3-epoxy pinane to carry out ring-opening rearrangement reaction, and obtaining the hydrated carvacrol with high yield and high purity under the combined action of the catalyst and the microchannel reactor; the method has mild reaction conditions and simple and convenient operation, can effectively avoid severe heat release of epoxy ring opening and generated byproducts, has high reaction efficiency, can reach 98 percent of product yield and 99 percent of content, and has good industrial application prospect.

Inventors

• ZHANG WANBIN
• CHEN JIANZHONG
• GUAN JING
• LI JINHUI
• WANG QIYUAN
• YANG HONGXIANG
• ZHANG XIAOXIAO
• LIU XIAOTAO

Assignees

• 上海交通大学
• 江苏宏邦化工科技有限公司

Dates

Publication Date

20260512

Application Date

20251223

Claims (6)

1. 1. A method for synthesizing hydrated carveol by using 2, 3-epoxy pinane is characterized by comprising the following steps of taking 2, 3-epoxy pinane as a raw material, taking organic phosphoric acid as a catalyst in a solvent, taking a micro-channel reactor as reaction equipment, adding deionized water, and enabling the 2, 3-epoxy pinane to undergo a ring-opening rearrangement reaction to obtain hydrated carveol; the organic phosphoric acid is selected from the following structures: 。
2. 2. The method for synthesizing carvacrol hydrate from 2, 3-epoxypinane according to claim 1, wherein the solvent is one or two of toluene, anisole, methanol, ethanol, cyclohexane, 1, 4-dioxane, tetrahydrofuran or dichloroethane.
3. 3. The method for synthesizing carvacrol hydrate by using 2, 3-epoxypinane according to claim 1, wherein the molar ratio of 2, 3-epoxypinane to organic phosphoric acid catalyst is 10000:1-5.
4. 4. The method for synthesizing carvacrol hydrate from 2, 3-epoxypinane according to claim 1, wherein the reaction temperature is 10-60 ℃.
5. 5. The method for synthesizing carvacrol hydrate from 2, 3-epoxypinane according to claim 1, wherein said microchannel reactor is a continuous flow microreactor.
6. 6. The method for synthesizing carveol hydrate from 2, 3-epoxypinane as claimed in claim 1, wherein the 2, 3-epoxypinane and the organic phosphoric acid catalyst are dissolved in a solvent respectively, and then are mixed uniformly at a temperature of-25-0 ℃ and then are conveyed to a microchannel reactor for reaction.

Description

Method for synthesizing hydrated carvacrol by using 2, 3-epoxy pinane Technical Field The invention belongs to the technical field of organic synthesis, relates to synthesis of hydrated carvacrol as an intermediate of medicines and spices, and in particular relates to a method for mildly synthesizing hydrated carvacrol in a micro-channel reactor by taking 2, 3-epoxy pinane as a raw material and utilizing an organic phosphoric acid catalyst. Background The hydrated carvacrol (Sobrerol), also known as Sobuterol, has a molecular formula of C 10H18O2, belongs to a terpene diol compound, is a mucolytic drug, has phlegm eliminating and asthma relieving effects, and is mainly used for treating bronchitis, asthma and other diseases. In recent years, the compound has pharmacological action of inducing tumor cell apoptosis, and is expected to become a new anticancer drug, in addition, the compound can be used as an intermediate of important perfume (such as carvacrol, carvone). The use of these compounds is increasing, and their synthesis has therefore been attracting attention. At present, three synthetic methods of hydrated carveol mainly exist, namely, 2, 3-epoxy pinane is used as a raw material most mainly and most commonly, and is subjected to acid catalysis or RuCl 3 catalysis ring opening in an aqueous phase (Tetrahedron, 1998, 54:593-598), the method has the defects of multiple side reactions, low chemical yield (less than 15 percent) and low optical purity of a product, and the other method adopts lipase catalysis to dynamically split a racemate to obtain an optical purity product, so that the method is not suitable for large-scale preparation (Tetrahedron Asymmetry,1991, 2:931-934). The third method is to use readily available 3, 5-dihydroxyl-4-methyl benzoate as a raw material to efficiently synthesize optically pure trans- (+) -hydrated pinanol through 7-step reaction (total yield is 27%). The method has the advantages of few side reactions, easy operation and high chemical yield and optical purity (ee > 99%), but the reaction has the defects of long steps, low total yield and the like (Chemical Journal of Chinese Universities,2004, 25:1069-1072), and limits the further application of the method in production. Disclosure of Invention Aiming at the defects of the prior art, the invention aims to provide a method for synthesizing hydrated carveol by using 2, 3-epoxy pinane, the method for synthesizing the carvacrol hydrate by combining the organic phosphoric acid catalyst with the continuous flow micro-channel technology has the advantages of mild reaction conditions, high chemical selectivity and yield and the like. The invention is realized by the following technical scheme: a method for synthesizing carveol hydrate by using 2, 3-epoxy pinane, comprising the following steps: 2, 3-epoxy pinane is taken as a raw material, organic phosphoric acid is taken as a catalyst in a solvent, a micro-channel reactor is taken as reaction equipment, deionized water is added, so that the 2, 3-epoxy pinane undergoes ring-opening rearrangement reaction, and hydrated carvacrol is obtained with high yield and high purity under the combined action of the catalyst and the micro-channel reactor; the organic phosphoric acid is selected from the following structures: 。 the reaction equation is: The invention further improves the scheme as follows: The solvent is one or two of toluene, anisole, methanol, ethanol, cyclohexane, 1, 4-dioxane, tetrahydrofuran or dichloroethane. Further, the molar ratio of the 2, 3-epoxy pinane to the organic phosphoric acid catalyst is 10000:1-5. Further, the reaction temperature is 10-60 ℃. Further, the microchannel reactor is a continuous flow microreactor. Further, the 2, 3-epoxy pinane and the organic phosphoric acid catalyst are required to be dissolved in a solvent respectively, then are uniformly mixed at the temperature of-25 to 0 ℃ and then are conveyed to a micro-channel reactor for reaction. Compared with the prior art, the invention has the beneficial effects that: The invention provides a brand new synthesis method of hydrated carvacrol, which utilizes the combined action of an organic phosphoric acid catalyst and a continuous flow micro-reaction channel, improves the chemical selectivity of the ring-opening rearrangement of 2, 3-epoxy pinane, reduces the adverse thermal effect influence caused by the ring-opening reaction, and provides a new way for obtaining the hydrated carvacrol with high yield. Drawings FIG. 1 is a flow chart of a continuous flow microreaction device of the present invention. Detailed Description The present invention will be described in detail with reference to specific examples. The invention provides a method for synthesizing carveol hydrate by using 2, 3-epoxy pinane, which comprises the following steps: 2, 3-epoxy pinane is dissolved in a solvent, an organic phosphoric acid catalyst is also dissolved in the solvent to prepare a solution with a certain concentra