阅读说明：本技术 一种制备二芳甲基烷基醚的新方法 (New method for preparing diaryl methyl alkyl ether ) 是由 谢新刚 吴光苗 厍学功 于 2019-11-28 设计创作，主要内容包括：本发明公开一种制备二芳甲基烷基醚的新方法,属于有机合成化学领域。该方法包括如下步骤：在室温开放体系下,将4-取代对亚甲基苯醌和5mol％四溴荧光素(Eosin Y)加入相应醇中。室温搅拌反应2-5小时,即以良好的收率得到相应二芳甲基烷基醚。本发明操作条件温和、绿色环保,不需要苛刻的除水除氧操作及装置,反应室温即可进行,底物转化率高,后处理简单易行,为目前制备二芳甲基烷基醚提供了一种良好的方法。(The invention discloses a new method for preparing diaryl methyl alkyl ether, belonging to the field of organic synthetic chemistry. The method comprises the following steps: 4-substituted p-methylenequinone and 5 mol% tetrabromofluorescein (Eosin Y) were added to the corresponding alcohol under an open system at room temperature. The reaction is stirred for 2 to 5 hours at room temperature, and the corresponding diaryl methyl alkyl ether is obtained with good yield. The method has mild operation conditions, is green and environment-friendly, does not need harsh water removal and oxygen removal operation and devices, can be carried out at room temperature, has high substrate conversion rate and simple and easy post-treatment, and provides a good method for preparing the diaryl methyl alkyl ether at present.)

1. a novel process for the preparation of a diarylmethyl alkyl ether characterized by the steps of:

(1) sequentially adding an organic solvent, 4-substituted p-methylene benzoquinone and tetrabromo fluorescein Eosin Y into an open glass flask, and stirring at room temperature for reaction for 2-5 hours;

(2) after the reaction is finished, the solvent is removed by evaporation under reduced pressure, and the obtained crude product is separated and purified by silica gel column chromatography.

2. A novel process for the preparation of diarylmethylalkyl ethers, characterized in that the substituents of the 4-substituted p-methylenebenzoquinone can be electron withdrawing substituents and electron donating substituents.

3. The process for preparing diarylmethylalkyl ethers of claim 1 wherein the organic solvents of step (1) are different alcohols.

4. The process for preparing diarylmethylalkyl ethers of claim 1 wherein the molar ratio of substituted p-methylenequinone to Eosin Y in step (1) is 1: 0.05.

Technical Field

The invention particularly relates to a novel method for preparing diaryl methyl alkyl ether, belonging to the field of organic synthetic chemistry.

Background

Ether compounds are widely found in nature and include some oligonucleotides and carbohydrate compounds with important activities. In recent years, diarylmethyl alkyl ethers have attracted attention from chemists and synthetic chemists, and this structure is considered to be the pharmacophore of some active drugs, for example, benztropine (benztropine), diphenylpyrine (diphenylpyrine), vancomycin (vanoxerin), etc. all contain diarylmethyl alkyl ether structures. The traditional preparation of diaryl methyl alkyl ether is realized by condensation reaction of corresponding alcohol, most of which uses a large amount of strong acid and strong base as promoters, and the preparation methods have low atom economy and do not meet the requirements of sustainable development. Other preparation methods using transition metal-containing Lewis acid as a catalyst can cause transition metal residues in the product and affect the quality of the final product.

In view of this, synthetic chemists have developed new methods in recent years to prepare diarylmethyl alkyl ethers, one of which is asymmetric diarylmethyl alkyl ethers prepared by 1, 6-addition reaction of alcohol and p-methylenebenzoquinone. In 2015, Chenchang national project group at Chongqing university reported a method for preparing diarylmethyl alkyl ethers using boron trifluoride diethyl etherate (adv. Synth. Catal.2015,357, 3115-3120), but unfortunately this method requires toluene as solvent, and is carried out under high temperature conditions of solvent reflux, which is not suitable for some substrates sensitive to heat; the use of strong Lewis acids boron trifluoride etherate also makes the substrate more narrow in its applicability. Through literature research, no report is found for preparing diarylmethyl alkyl ether by promoting 1, 6-addition reaction of alcohol and p-methylenebenzoquinone by using tetrabromofluorescein (Esoin Y) as a catalyst.

Disclosure of Invention

The technical scheme adopted by the invention is as follows:

a novel process for the preparation of a diarylmethyl alkyl ether comprising

(1) Sequentially adding p-methylenequinone, corresponding alcohol and Eosin Y into an open glass flask, and reacting for 2-5 hours under the condition of open stirring at room temperature;

(2) after the reaction is finished, the alcohol solvent is distilled off under reduced pressure, and the obtained crude product is separated and purified by silica gel column chromatography.

Further, the p-methylene benzoquinone substituent may be an electron-withdrawing substituent and an electron-donating substituent.

Further, the organic solvent in the step (1) is corresponding alcohol.

Furthermore, the molar ratio of the p-methylene benzoquinone to the Eosin Y in the step (1) is 1: 0.05.

The method has the advantages of simple reaction conditions, environmental protection, no need of harsh water removal and oxygen removal operation and device, room-temperature reaction, high substrate conversion rate, simple and feasible post-treatment, and provides a good method for preparing the diaryl methyl alkyl ether at present.

Detailed Description

The present invention is further illustrated by the following examples.

(1) Example 1

The specific experimental process is as follows: to a 10mL glass flask, 1(0.5mmol) and Eosin Y (0.025mmol) were added, and dissolved in 4mL of methanol. The resulting mixture was stirred in an open system at room temperature for 3 hours, methanol was removed under reduced pressure, and the resulting crude product was subjected to separation and purification by silica gel column chromatography to give 1a in a yield of 95%. The characterization of the product 1a obtained is as follows: a white solid; the melting point is 88-90 ℃;¹H NMR(400MHz,CDCl₃)δ7.54–7.35(m,5H),5.29(d,J＝14Hz,2H),3.51(s,1H),1.55(s,18H)ppm；¹³C NMR(101MHz,CDCl₃)δ153.1,142.4,135.6,132.5,128.3,127.2,126.9,123.8,86.0,57.0,34.3,30.2ppm。

(2) example 2

Yield 78%, characterization of the obtained product 1b as follows: a yellow oily liquid;¹H NMR(300MHz,CDCl₃)δ7.40–7.18(m,5H),7.113(s,2H),5.28(s,1H),5.11(s,1H),3.51(q,J＝7.0Hz,2H),1.39(s,18H),1.26(t,J＝9.2Hz,3H)ppm；¹³C NMR(101MHz,CDCl₃)δ153.1,142.3,135.6,132.5,128.3,127.2,126.9,123.8,86.03,57.04,34.30,30.25ppm。

(3) in the case of the example 3, the following examples are given,

yield 72% and characterization of the product 2a obtained as follows: a yellow oily liquid;¹H NMR(300MHz,CDCl₃)δ7.19(d,J＝8.6Hz,4H),5.12(d,J＝6.8Hz,2H),3.35(s,3H),2.32(s,3H),1.40(s,18H)ppm；¹³C NMR(75MHz,CDCl₃)δ153.3,139.7,139.0,135.8,133.0,129.3,127.1,124.0,86.2,57.2,34.6,30.5,21.4ppm。

(4) in the case of the example 4, the following examples are given,

yield 68% and characterization of the product 2b obtained as follows: a yellow oily liquid;¹H NMR(300MHz,CDCl₃)δ7.27–7.22(m,2H),7.13(d,J＝8.4Hz,4H),5.25(s,1H),5.10(s,1H),3.50(q,J＝7.2Hz,2H),2.32(s,3H),1.39(s,18H),1.25(t,3H)ppm；¹³C NMR(101MHz,CDCl₃)δ153.0,139.9,136.6,135.5,128.9,126.9,123.8,83.9,64.4,34.3,30.3,21.1,15.4ppm。

(5) in the case of the example 5, the following examples were conducted,

yield 86%, characterization of the obtained product 3a as follows: a yellow oily liquid;¹H NMR(400MHz,CDCl₃)δ7.30–7.25(m,2H),7.10(s,2H),6.87(m,2H),5.12(s,2H),3.79(s,3H),3.34(s,3H),1.40(s,18H).¹³C NMR(101MHz,CDCl₃)δ158.8,153.1,135.6,134.6,132.7,128.2,123.7,113.7,85.6,56.9,55.2,34.3,30.3ppm。

(6) in the case of the example 6, it is shown,

yield 82%, characterization of the obtained product 3b as follows: a yellow oily liquid;¹H NMR(300MHz,CDCl₃)δ7.31–7.24(m,2H),7.11(s,2H),6.91–6.83(m,2H),5.11(d,J＝3.6Hz,2H),3.79(s,3H),1.40(s,18H),1.29–1.18(q,J＝7.2Hz,3H).¹³C NMR(101MHz,CDCl₃)δ159.8,154.3,135.4,134.5,133.7,127.3,124.6,114.6,84.6,57.4,54.3,34.5,31.3,17.2ppm。

(7) in the case of the example 7, the following examples are given,

yield 68% and characterization of the obtained product 4a as follows: white solid, melting point: 104-105 ℃;¹H NMR(300MHz,CDCl₃)δ7.29(d,J＝0.9Hz,3H),7.07(s,2H),5.14(d,J＝8.0Hz,2H),3.34(d,J＝0.9Hz,3H),1.40(d,J＝0.9Hz,18H)ppm；¹³C NMR(75MHz,CDCl₃)δ153.29,141.02,135.76,132.00,128.30,123.74,85.28,57.00,34.32,30.23ppm。

(8) in the case of the example 8, the following examples are given,

yield 52%, characterization of the obtained product 4b as follows: a light yellow oily liquid;¹H NMR(300MHz,CDCl₃)δ7.31–7.28(m,4H),7.08(s,2H),5.24(s,1H),5.14(s,1H),3.49(q,J＝7.0Hz,2H),1.40(s,18H),1.25(t,J＝7.2Hz,3H)ppm.¹³C NMR(75MHz,CDCl₃)δ153.40,141.23,135.69,132.37,128.31,123.80,83.27,64.51,34.31,30.24,15.36ppm。