阅读说明：本技术 一锅法制备4-正丁基间苯二酚的方法 (Method for preparing 4-n-butylresorcinol by one-pot method ) 是由 张克伦 张太军 于 2019-11-25 设计创作，主要内容包括：本发明公开了一锅法制备4-正丁基间苯二酚的方法,属于化妆品中间体合成领域。以间二苯酚为原料,在正丁醇中与碱反应经过成单酚盐,然后与路易斯酸脱水一锅法反应,酸解后得到粗品,接着重结晶得到4-正丁基间苯二酚。该方法操作简便,条件温和,成本低廉,收率高,得到的产品纯度可达99.0％以上,具备潜在的放大前景。(The invention discloses a method for preparing 4-n-butylresorcinol by a one-pot method, belonging to the field of synthesis of cosmetic intermediates. The method comprises the steps of taking resorcinol as a raw material, reacting with alkali in n-butyl alcohol to obtain monophenolate, then reacting with Lewis acid in a one-pot dehydration method to obtain a crude product after acidolysis, and then recrystallizing to obtain 4-n-butylresorcinol. The method has the advantages of simple operation, mild conditions, low cost and high yield, and the obtained product has the purity of more than 99.0 percent and has potential amplification prospect.)

1. The method for preparing 4-n-butylresorcinol by a one-pot method is characterized by comprising the following steps of: reacting resorcinol with alkali to obtain resorcinol monophenolate, adding Lewis acid catalyst, n-butanol and organic solvent for dehydration friedel-crafts reaction, and treating to obtain 4-n-butyl resorcinol.

2. The one-pot method for synthesizing 4-n-butylresorcinol according to claim 1, wherein: the alkali is selected from sodium hydroxide, potassium hydroxide, sodium hydride, n-butyl lithium, n-butyl sodium alkoxide or n-butyl potassium alkoxide.

3. The one-pot method for synthesizing 4-n-butylresorcinol according to claim 1, wherein: the organic solvent is selected from toluene, dioxane, heptane, cyclohexane, NMP, chlorobenzene or xylene.

4. The one-pot method for synthesizing 4-n-butylresorcinol according to claim 1, wherein: the Lewis acid catalyst is selected from zinc chloride, ferric trichloride, triphenylboron or (C)₆F₅)₃B。

5. The one-pot method for synthesizing 4-n-butylresorcinol according to claim 1, wherein: in the dehydration friedel-crafts reaction, initiator is added to facilitate the start of the reaction, and the initiator is concentrated sulfuric acid, anhydrous calcium chloride or anhydrous copper sulfate.

6. The one-pot method for synthesizing 4-n-butylresorcinol according to claim 1, wherein: the mol ratio of the resorcinol to the alkali to the Lewis acid catalyst is 1:1-1.03: 0.1-0.6.

Technical Field

The invention relates to a method for preparing 4-n-butylresorcinol by a one-pot method, belonging to the technical field of chemical intermediate synthesis.

Background

4-n-butylresorcinol, alias 4-butylresorcinol, England name 4-butyl-resorcinol, and molecular formula C₁₀H₁₄O₂The molecular weight is 166.22, CAS is 18979-61-8, is commonly used as a whitening additive of a skin care product, can be used for synthesizing FXR agonist intermediates, treating diseases such as cholestasis, hypercholesterolemia, heart disease and the like, and is mainly used in the fields of spices, medicines, dyes and the like.

At present, the synthesis method of the product literature is mainly to synthesize resorcinol and n-butyric acid in AlCl₃The Friedel-crafts acylation reaction is carried out under catalysis, and the carbonyl is reduced into methylene by utilizing Wolff-Kishner-Huang Minlon or Clemmen sen reduction reaction to obtain the 4-butyl resorcinol with the total yield of 44%. Reference: bioorg.med.chem.2014,22, 1596-.

However, the carbonyl group is reduced to methylene group by Wolff-Kishner-yellow dragon reaction or Clemmensen reduction reaction, and a large amount of hydrazine or zinc amalgam is used, so that the production safety is reduced, the environment is polluted, mercury reagent with high toxicity is used, and the purchase is limited during the amplification.

Aiming at the defects of the method, the method is improved in process route so as to be suitable for an industrial scale-up method.

Disclosure of Invention

In order to overcome the technical defects, the invention discloses a method for preparing 4-butyl resorcinol by a one-pot method, which comprises the steps of taking resorcinol as a raw material, reacting with alkali in n-butyl alcohol to obtain monophenolate, then reacting with Lewis acid by a one-pot dehydration method, carrying out acidolysis to obtain a crude product, and then recrystallizing to obtain the 4-n-butyl resorcinol. The method has the advantages of simple operation, mild conditions, low cost and high yield, and the obtained product has the purity of more than 99.0 percent and has potential amplification prospect.

The method for preparing 4-n-butylresorcinol by the one-pot method comprises the following steps:

the preparation method comprises the steps of obtaining resorcinol mono-lithium/sodium/potassium salt by using resorcinol and alkali, then carrying out dehydration friedel-crafts reaction on resorcinol and n-butanol and a Lewis acid catalyst in an organic solvent, obtaining a crude product of 4-n-butyl resorcinol after the reaction is finished and carrying out acidolysis, and recrystallizing to obtain a pure product of 4-butyl resorcinol.

Further, in the above technical solution, the base is selected from sodium hydroxide, potassium hydroxide, sodium hydride, n-butyl lithium, sodium n-butoxide or potassium n-butoxide.

Further, in the above technical solution, the solvent is selected from toluene, dioxane, heptane, cyclohexane, NMP, chlorobenzene, or xylene.

Further, in the above technical solution, the Lewis acid catalyst is selected from zinc chloride, ferric chloride, triphenylborane or (C)₆F₅)₃B。

Further, in the above technical scheme, in the dehydration friedel-crafts reaction, an initiator is added to facilitate the start of the reaction, and the initiator is concentrated sulfuric acid, anhydrous calcium chloride or anhydrous copper sulfate.

Further, in the technical scheme, the molar ratio of the resorcinol to the alkali to the Lewis acid catalyst is 1:1-1.03: 0.1-0.6.

Further, in the above technical scheme, the recrystallization conditions are 6 times volume of water, 5% of activated carbon and 2% of sodium thiosulfate are refluxed, and the mixture is subjected to heat filtration, cooling and crystallization.

Further, in the above technical scheme, the initiator is added in the dehydration reaction to facilitate the start of the reaction, and the initiator is concentrated sulfuric acid, anhydrous calcium chloride or anhydrous copper sulfate. The initiator is added in an amount of 0.05 to 0.1 eq.

Advantageous effects of the invention

According to the invention, the 4-n-butylresorcinol is prepared by adopting a one-pot method, one hydroxyl group is changed into a stronger electron-donating positioning group, and then the appropriate catalyst and n-butanol are adopted for dehydration and selective positioning, so that the 4-n-butylresorcinol is obtained, and the method has the advantages of simple operation, high atom utilization rate, mild conditions, low cost and high yield, and has an industrial amplification production prospect through process verification.

DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION