CN112920096A - Method for preparing 2-methyl-4- (benzenesulfonyl) -2-butanol - Google Patents

Abstract

The invention provides a method for preparing 2-methyl-4- (benzenesulfonyl) -2-butanol, which comprises the following steps: with sodium benzene sulfinate and halogenated five-carbon alcohol (X-C)₅-OH) as a raw material, and reacting under the action of a catalyst tetrabutylammonium bromide to obtain the target product. The method provided by the invention has the advantages of easily obtained raw materials, mild reaction conditions, simple post-treatment, easy realization of industrialization and the like, and is a good method for synthesizing 2-methyl-4- (benzenesulfonyl) -2-butanol.

Description

Method for preparing 2-methyl-4- (benzenesulfonyl) -2-butanol

Technical Field

The invention relates to a preparation method of 2-methyl-4- (benzenesulfonyl) -2-butanol.

Background

2-methyl-4- (benzenesulfonyl) -2-butanol (I) can be used for synthesizing 25-hydroxy vitamin D₃And 1 alpha, 25-dihydroxyvitamin D₃(pL190804B₁20060228). 25-hydroxy vitamin D₃And 1 alpha, 25-dihydroxyvitamin D₃The vitamin D is the main existing form of vitamin D in human bodies, has wide physiological effect, is an essential substance for maintaining human health and cell growth and development, has obvious activity of regulating calcium and phosphorus metabolism, can promote the absorption and transportation of phosphorus by small intestinal mucosa, and simultaneously promotes the reabsorption of calcium and phosphorus by renal tubules. In the skeleton, it can promote the calcification of new bone and the liberation of calcium from old bone marrowSo that the bone substance is continuously renewed, and the balance of blood and calcium can be maintained at the same time, thus being the necessary raw material for bone building. Therefore, the research on the synthesis method of the 2-methyl-4- (benzenesulfonyl) -2-butanol has practical application value.

The existing method for synthesizing 2-methyl-4- (benzenesulfonyl) -2-butanol is as follows:

sodium hydride is used in the route, and the sodium hydride has high chemical reactivity and can be spontaneously combusted in humid air. The heat or the contact with moisture and acid releases the heat and hydrogen to cause combustion and explosion. Can react strongly with the oxidant to cause combustion or explosion. Generates hydroxide when meeting moisture and water, and has strong corrosiveness. Meanwhile, the reaction with a substrate is quite violent, so the whole reaction process needs to be carried out under the protection of low temperature (dry ice and acetone cold trap) and inert gas (high-purity nitrogen or high-purity argon, 99.99 percent, and the high-purity argon is the first choice); the excessive and unreacted sodium hydride is required to be gradually added into anhydrous isopropanol or anhydrous n-butanol, the mixture is kept stand for 24 hours, the mixture is diluted and then put into a wastewater system, and strict anhydrous treatment is carried out by using a reaction system of the sodium hydride, a solvent and the like. Therefore, this method is not suitable for large-scale industrial production and is not a preferred method. Therefore, it is important to develop a novel method for preparing 2-methyl-4- (benzenesulfonyl) -2-butanol.

Disclosure of Invention

The invention aims to disclose a novel method for synthesizing 2-methyl-4- (benzenesulfonyl) -2-butanol, which can be used for synthesizing 25-hydroxy vitamin D₃And 1 alpha, 25-dihydroxyvitamin D₃Is a useful intermediate.

The invention designs a synthetic route for preparing 2-methyl-4- (benzenesulfonyl) -2-butanol, which comprises the following steps: with sodium benzene sulfinate and halogenated five-carbon alcohol (X-C)₅-OH) as a raw material, and reacting under the action of a catalyst tetrabutylammonium bromide to obtain the target 2-methyl-4- (benzenesulfonyl) -2-butanol. The synthetic route is as follows:

the synthetic method for preparing 2-methyl-4- (benzenesulfonyl) -2-butanol comprises the following steps:

adding N, N-Dimethylformamide (DMF) into a three-neck flask, adding sodium benzene sulfinate while stirring, and adding tetrabutylammonium bromide (catalyst tetrabutylammonium bromide is X-C)₅2% -10% of the mass of-OH), and then adding halogenated five-carbon alcohol X-C₅-OH dropping into three-necked bottle (wherein X-C₅The molar ratio of-OH to sodium benzene sulfinate is 1: 1.2-2.0), and the reaction is carried out for 2.5-7 h at the temperature of 30-100 ℃. TLC (petroleum ether: ethyl acetate: 5: 1, R)_f0.52) the end of the reaction was detected.

After the reaction liquid is cooled to room temperature, adding ethyl acetate into the reaction system, then respectively washing with water and saturated saline solution, and adding a proper amount of anhydrous Na after washing₂SO₄Drying, evaporating the solvent, and separating and purifying by column chromatography, wherein the mobile phase is petroleum ether: ethyl acetate ═ 20: 1, and the yield is 70-80.4%.

Detailed Description

The present invention will be described in further detail with reference to specific examples. Reagents, equipment and methods employed in the present invention are reagents, equipment and methods conventionally commercially available in the art and conventionally used methods, unless otherwise specified.

Example 1

Feeding molar ratio: I-C₅-OH: sodium benzene sulfinate ═ 1: 1.5 solvent: DMF (drying)

500ml of a three-necked flask was charged with 23.3g (0.142mol) of sodium benzenesulfinate (fully ground to a powder) and 1.5g of tetrabutylammonium bromide (catalyst tetrabutylammonium bromide is I-C)₅5% of-OH by mass), 200ml of DMF was added, and the mixture was stirred and warmed up to an external temperature of about 70 ℃ at an internal temperature of about 60 ℃ to obtain 20.2g (0.0944mol) of I-C₅Dropping OH into a three-necked flask, maintaining the temperature, and reacting for 4 hours.

After the reaction solution was cooled, 150ml of ethyl acetate was added, followed by washing with 4X 50ml of water and 2X 30ml of saturated sodium chloride, drying, filtering, and evaporation of the solvent. Chromatographic columnSeparation and purification treatment (two points are main products, and a product with high polarity is taken as a point), wherein a mobile phase is petroleum ether: ethyl acetate ═ 20: 1, 20.1g of pure product is obtained, yield 74.4%. Nuclear magnetic data for 2-methyl-4- (benzenesulfonyl) -2-butanol:¹H NMR(400MHz,cdcl₃)δ7.93–7.84(m,2H),7.67–7.60(m,1H),7.55(td,J＝8.1,0.7Hz,2H),3.26–3.19(m,2H),1.89–1.80(m,2H),1.19(s,6H)。

Claims (1)

1. a method for preparing 2-methyl-4- (benzenesulfonyl) -2-butanol, comprising:

using sodium benzene sulfinate and halogenated five-carbon alcohol (X-C)₅-OH) to obtain the target product 2-methyl-4- (benzenesulfonyl) -2-butanol, wherein the reaction formula is as follows:

the reaction steps are as follows: adding anhydrous treated N, N-Dimethylformamide (DMF) into a three-neck flask, adding sodium benzene sulfinate while stirring, and adding tetrabutylammonium bromide (catalyst tetrabutylammonium bromide is X-C)₅2% -10% of the mass of-OH), followed by the addition of X-C₅-OH dropping into three-necked bottle (wherein X-C₅The molar ratio of-OH to sodium benzene sulfinate is 1: 1.2-2.0), the reaction is carried out for 2.5-7 h at the temperature of 30-100 ℃, and TLC (petroleum ether: ethyl acetate ═ 5: 1, R_f0.52) detecting the end point of the reaction;

after the reaction liquid is cooled to room temperature, adding ethyl acetate into the reaction system, then respectively washing with water and saturated saline solution, and adding a proper amount of anhydrous Na after washing₂SO₄Drying, evaporating the solvent, and separating and purifying by column chromatography, wherein the mobile phase is petroleum ether: ethyl acetate ═ 20: 1, and the yield is 70-80.4%.