阅读说明：本技术 3-甲基-5-(2,2,3-三甲基-3-环戊烯-1-基)戊-4-烯-2-醇的制备 (Preparation of 3-methyl-5- (2,2, 3-trimethyl-3-cyclopenten-1-yl) pent-4-en-2-ol ) 是由 黄旺生 胡建良 李志江 张晓龙 范宇鹏 史波涛 林传明 朱超 范亚新 徐胜辉 厉 于 2019-09-29 设计创作，主要内容包括：本发明提供了一种3-甲基-5-(2,2,3-三甲基-3-环戊烯-1-基)戊-4-烯-2-醇的制备方法,通过首先将式(III)结构的化合物转化为式(IV)结构的化合物,然后再将式(IV)结构的化合物转化为式(I)结构的化合物,其中,本发明通过将(III)结构的化合物在同一反应体系中实现异构化与甲基化反应得到式(IV)结构的化合物,使得得到的产物的纯度高,收率高,且简化了反应的步骤,可以实现工业化生产。(The invention provides a preparation method of 3-methyl-5- (2,2, 3-trimethyl-3-cyclopentene-1-yl) pent-4-ene-2-ol, which comprises the steps of firstly converting a compound with a structure shown in a formula (III) into a compound with a structure shown in a formula (IV), and then converting the compound with the structure shown in the formula (IV) into a compound with a structure shown in a formula (I), wherein the compound with the structure shown in the formula (IV) is obtained by carrying out isomerization and methylation on the compound with the structure shown in the formula (III) in the same reaction system, so that the obtained product has high purity and yield, the reaction steps are simplified, and the industrial production can be realized.)

1. A process for the preparation of 3-methyl-5- (2,2, 3-trimethyl-3-cyclopenten-1-yl) pent-4-en-2-ol comprising:

1) converting the compound with the structure of the formula (III) into the compound with the structure of the formula (IV).

2) Converting the compound with the structure of the formula (IV) into the compound with the structure of the formula (I),

2. the method according to claim 1, wherein the compound having the structure of formula (III) is prepared by the following method:

mixing campholenic aldehyde and acetone for reaction to obtain the compound with the structure of the formula (III).

3. The preparation method according to claim 2, wherein the catalyst for the reaction is one or more of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, morpholine, pyridine and pyrrole.

4. The preparation method according to claim 1, wherein the step 1) is specifically:

and (3) carrying out isomerization reaction and methylation reaction on the compound with the structure of the formula (III) to obtain the compound with the structure of the formula (IV).

5. The method according to claim 4, wherein the solvent for the reaction is one or more selected from water, toluene, xylene, cyclopentane, cyclohexane, N-dimethylformamide, tetrahydrofuran, methyltetrahydrofuran, dimethyl sulfoxide, diethyl ether and carbon tetrachloride.

6. The preparation method according to claim 4, wherein the catalyst for the reaction is one or more of sodium hydroxide, potassium hydroxide, sodium amide, sodium hydride, sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, sodium trityl, lithium diisopropylamide, sodium methoxide, sodium ethoxide, sodium tert-butoxide and potassium tert-butoxide.

7. The preparation method of claim 4, wherein the molar ratio of the compound with the structure of the formula (III) to the catalyst is 1: 1-3.

8. The method of claim 4, wherein the methylating agent used in the methylation reaction is methyl chloride, methyl bromide or methyl iodide.

9. The preparation method of claim 6, wherein the molar ratio of the catalyst for the reaction to the methylating agent for the methylation reaction is 1: 0.85-1.15.

10. The preparation method according to claim 1, wherein the reducing agent for the conversion reaction in step 2) is one or more of sodium borohydride, potassium borohydride, aluminum sec-butoxide and aluminum isopropoxide.

Technical Field

The invention relates to the field of organic synthesis, in particular to a preparation method of 3-methyl-5- (2,2, 3-trimethyl-3-cyclopentene-1-yl) pent-4-ene-2-ol.

Background

3-methyl-5- (2,2, 3-trimethyl-3-cyclopenten-1-yl) pent-4-en-2-ol [ CAS number

67801-20-1], has strong fragrance of lignum Santali albi, radix aucklandiae and Moschus, and can be widely used in lignum Santali albi and radix aucklandiae type daily chemical essence formula.

In 1986, Naipawer Richard et al, which uses campholenic aldehyde as a raw material, condensed with 2-butanone, isomerized the condensation product with potassium tert-butoxide in dimethylformamide to translocate the double bond, and finally reduced with sodium borohydride to obtain a product (EP0203528), easily obtain a byproduct, and have difficulty in separation from a target product, so that the obtained product has low purity and low yield; the specific reaction steps are as follows: wherein, the compound I is the target product 3-methyl-5- (2,2, 3-trimethyl-3-cyclopenten-1-yl) pent-4-en-2-ol, and the product II is impurity.

Disclosure of Invention

In view of the above, the technical problem to be solved by the present invention is to provide a method for preparing 3-methyl-5- (2,2, 3-trimethyl-3-cyclopenten-1-yl) pent-4-en-2-ol, which has high yield and high purity.

The invention provides a preparation method of 3-methyl-5- (2,2, 3-trimethyl-3-cyclopentene-1-yl) pent-4-ene-2-alcohol, which comprises the following steps:

1) converting the compound with the structure of the formula (III) into a compound with the structure of the formula (IV),

2) converting the compound with the structure of the formula (IV) into the compound with the structure of the formula (I),

preferably, the compound with the structure of the formula (III) is prepared according to the following method:

mixing campholenic aldehyde and acetone for reaction to obtain the compound with the structure of the formula (III).

Preferably, the catalyst for the reaction is one or more of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, morpholine, pyridine and pyrrole.

Preferably, the step 1) is specifically:

and (3) carrying out isomerization reaction and methylation reaction on the compound with the structure of the formula (III) to obtain the compound with the structure of the formula (IV).

Preferably, the solvent for the reaction is one or more of water, toluene, xylene, cyclopentane, cyclohexane, N-dimethylformamide, tetrahydrofuran, methyltetrahydrofuran, dimethyl sulfoxide, diethyl ether and carbon tetrachloride.

Preferably, the catalyst for the reaction is one or more of sodium hydroxide, potassium hydroxide, sodium amide, sodium hydride, sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, trityl sodium, lithium diisopropylamide, sodium methoxide, sodium ethoxide, sodium tert-butoxide and potassium tert-butoxide.

Preferably, the molar ratio of the compound with the structure of the formula (III) to the catalyst is 1 to (1-3).

Preferably, the methylating agent for the methylation reaction is methyl chloride, methyl bromide or methyl iodide.

Preferably, the molar ratio of the catalyst for the reaction to the methylating agent for the methylation reaction is 1: (0.85-1.15).

Preferably, the reducing agent for the conversion reaction in step 2) is one or more of sodium borohydride, potassium borohydride, aluminum sec-butoxide and aluminum isopropoxide.

Compared with the prior art, the invention provides a preparation method of 3-methyl-5- (2,2, 3-trimethyl-3-cyclopentene-1-yl) pent-4-ene-2-ol, which comprises the steps of firstly converting a compound with a structure in a formula (III) into a compound with a structure in a formula (IV), and then converting the compound with the structure in the formula (IV) into a compound with a structure in a formula (I), wherein the compound with the structure in the formula (III) is subjected to isomerization and methylation in the same reaction system to obtain the compound with the structure in the formula (IV), so that the obtained product has high purity and yield, the reaction steps are simplified, and the industrial production can be realized.

Drawings

FIG. 1 is a mass spectrum of 3-methyl-5- (2,2, 3-trimethyl-3-cyclopenten-1-yl) pent-4-en-2-one obtained by the present invention;

FIG. 2 is a mass spectrum of 3-methyl-5- (2,2, 3-trimethyl-3-cyclopenten-1-yl) pent-4-en-2-ol obtained in the present invention.

Detailed Description

The invention provides a preparation method of 3-methyl-5- (2,2, 3-trimethyl-3-cyclopentene-1-yl) pent-4-ene-2-alcohol, which comprises the following steps:

1) converting the compound with the structure of the formula (III) into a compound with the structure of the formula (IV),

2) converting the compound with the structure of the formula (IV) into the compound with the structure of the formula (I),

according to the invention, the compound (5- (2,2, 3-trimethyl-3-cyclopenten-1-yl) pent-3-en-2-one) with the structure of formula (III) is converted into the compound (3-methyl-5- (2,2, 3-trimethyl-3-cyclopenten-1-yl) pent-4-en-2-one) with the structure of formula (IV), wherein the reaction is specifically as follows: carrying out isomerization reaction and methylation reaction on the compound with the structure of the formula (III) to obtain a compound with the structure of a formula (IV); the solvent for the reaction is preferably one or more of water, toluene, xylene, cyclopentane, cyclohexane, N-dimethylformamide, tetrahydrofuran, methyltetrahydrofuran, dimethyl sulfoxide, diethyl ether and carbon tetrachloride; more preferably cyclohexane or cyclopentane; the catalyst for the reaction is preferably one or more of sodium hydroxide, potassium hydroxide, sodium amide, sodium hydride, sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, trityl sodium, lithium diisopropylamide, sodium methoxide, sodium ethoxide, sodium tert-butoxide and potassium tert-butoxide, and more preferably one or more of sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, sodium tert-butoxide and potassium tert-butoxide; the methylation reagent for the methylation reaction is halogenated alkane, preferably methyl chloride, methyl bromide or methyl iodide; the molar ratio of the compound with the structure shown in the formula (III) to the catalyst is preferably 1 to (1-3), and more preferably 1 to (2-2.5); the molar ratio of the catalyst for the reaction to the methylating agent for the methylation reaction is preferably 1 to (0.85-1.15), and more preferably 1 to (1-1.1); more specifically, the reaction is: mixing the structure of the formula (III) with a solvent, adding a catalyst to perform an isomerization reaction, and after the isomerization is finished, continuously adding a methylation reagent into the system to perform a methylation reaction to obtain a compound of the structure of the formula (IV); a phase transfer catalyst can be added in the reaction, and the phase transfer catalyst can be one or more of benzyl triethyl ammonium chloride (TEBA), tetrabutyl ammonium bromide, tetrabutyl ammonium chloride, tetrabutyl ammonium hydrogen sulfate (TBAB), trioctyl methyl ammonium chloride, dodecyl trimethyl ammonium chloride, tetradecyl trimethyl ammonium chloride, chain polyethylene glycol dialkyl ether and cyclodextrin.

In the present invention, the present invention has no special requirement on the compound with the structure of formula (III), and preferably, the compound with the structure of formula (III) is prepared according to the following method:

mixing campholenic aldehyde and acetone for reaction to obtain a compound with a structure shown in a formula (III); wherein, the solvent of the reaction is one or more of water, toluene, xylene, cyclohexane, DMF (N, N-dimethylformamide), THF (tetrahydrofuran), methyltetrahydrofuran, DMSO (dimethyl sulfoxide), diethyl ether and carbon tetrachloride, and more preferably water or tetrahydrofuran; the catalyst for the reaction is preferably one or more of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, morpholine, pyridine and pyrrole; the molar ratio of the campholenic aldehyde to the acetone is 1: (1-4); the reaction temperature is preferably-10-60 ℃, and more preferably 10-50 ℃.

According to the invention, the compound with the structure of the formula (IV) is also converted into the compound (3-methyl-5- (2,2, 3-trimethyl-3-cyclopenten-1-yl) pent-4-en-2-ol) with the structure of the formula (I); wherein, the solvent of the reaction is preferably one or more of water, toluene, xylene, cyclohexane, DMF (N, N-dimethylformamide), methanol, ethanol, N-propanol, isopropanol, N-butanol, sec-butanol, THF (tetrahydrofuran), methyltetrahydrofuran, DMSO (dimethyl sulfoxide), diethyl ether and carbon tetrachloride; the reducing agent for the conversion reaction is one or more of sodium borohydride, potassium borohydride, aluminum sec-butoxide and aluminum isopropoxide, and more preferably sodium borohydride or potassium borohydride.

Specifically, the preparation method comprises the following process flows:

the preparation method of the 3-methyl-5- (2,2, 3-trimethyl-3-cyclopentene-1-yl) pent-4-ene-2-ol provided by the invention comprises the steps of firstly converting the compound with the structure of the formula (III) into the compound with the structure of the formula (IV), and then converting the compound with the structure of the formula (IV) into the compound with the structure of the formula (I), wherein the compound with the structure of the formula (IV) is obtained by carrying out isomerization and methylation on the compound with the structure of the formula (III) in the same reaction system, so that the obtained product has high purity and yield, the reaction steps are simplified, and the industrial production can be realized.

The following will clearly and completely describe the technical solutions of the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.