CN111793053A

CN111793053A - Preparation method of 9, 9-dimethyl xanthene

Info

Publication number: CN111793053A
Application number: CN202010818579.8A
Authority: CN
Inventors: 郑付伟; 韩福娇; 陈海涛; 李德锦; 杨柳; 王文新
Original assignee: Institute of Chemistry Henan Academy of Sciences Co Ltd; Henan Academy of Sciences
Current assignee: Institute of Chemistry Henan Academy of Sciences Co Ltd; Henan Academy of Sciences
Priority date: 2020-08-14
Filing date: 2020-08-14
Publication date: 2020-10-20

Abstract

The invention relates to a safe and efficient preparation method of an important raw material 9, 9-dimethyl xanthene of an industrial catalyst Xantphos, belonging to the technical field of fine chemical engineering. The preparation method takes diphenyl ether, acetone and an acid catalyst as raw materials, and the molar ratio of the raw materials is 1: 1: 2-5, preparing 9, 9-dimethyl xanthene by a one-pot method, wherein the yield can reach 70-75%, and the content is more than 99%. The method adopts acid-catalyzed activated acetone and diphenyl ether to carry out electrophilic substitution reaction to replace the extremely dangerous reaction of trimethyl aluminum and xanthone in the traditional process, and has the characteristics of cheap and easily-obtained raw materials, safe operation, high reaction speed, low requirement on production equipment and the like. The invention greatly reduces the production difficulty of the product and can quickly improve the yield of the 9, 9-dimethyl xanthene.

Description

Preparation method of 9, 9-dimethyl xanthene

Technical Field

The invention belongs to the technical field of fine chemical engineering, and relates to a preparation method of 9, 9-dimethyl xanthene.

Background

The 9, 9-dimethyl xanthene is an important fine chemical intermediate, is mainly used for preparing an industrial phosphorus ligand catalyst 4, 5-bis (diphenylphosphino) -9, 9-dimethyl xanthene (xanthhos), and a derivative of the 9, 9-dimethyl xanthene has excellent hole transport performance, can also be used in the fields of liquid crystal materials, solar cells, catalytic materials and the like, and particularly, a downstream product of the xanthene is widely applied to coupling reactions of palladium-catalyzed Suzuki (Suzuki), Negishi (Negishi), Stille (Stille), Heck (Heck) and the like by virtue of a special structure. With the annual increase in the demand of Xantphos in the pharmaceutical and optoelectronic material industries, the annual demand for the phosphorus ligand in the market is expected to be over 20 tons in the coming years.

In the prior art, few research reports are reported on the synthesis of 9, 9-dimethylxanthene, and at present, the following three methods are mainly used for preparation: 1. prepared by nucleophilic reaction of trimethylaluminum with xanthone (Chinese Journal of Polymer science,36(2), 244-; 2. prepared by a two-step reaction using diphenyl ether, 2-diiodopropane and n-butyllithium (WO 2009013525); 3. prepared by a two-step reaction of 2- (2-bromophenyl) -2-propanol with phenol in the presence of a catalyst (RSC Advances,6(25), 20588-. The first two processes of the three preparation processes need to use flammable and explosive dangerous goods such as trimethylaluminum and n-butyllithium, so that the two processes have extremely harsh reaction conditions, very dangerous production process and need special equipment to carry out industrial production, thereby greatly limiting the capacity of 9, 9-dimethylxanthene. The third process has high raw material cost, long production period and low yield, and is not beneficial to the preparation of 9, 9-dimethyl xanthene, so that the 9, 9-dimethyl xanthene capacity in the current market is insufficient, the internal Xantphos capacity is also insufficient, and a large amount of market vacancy is generated. At present, a new method suitable for industrial production is urgently needed to be developed.

Disclosure of Invention

In order to overcome the defects of large operation risk, high requirement on production equipment and low production efficiency in the existing 9, 9-dimethylxanthene production process, the invention aims to provide a safe and efficient preparation method of 9, 9-dimethylxanthene, which solves the problems of high risk, high requirement on equipment, low production efficiency and the like in the production process.

The invention solves the technical problem by adopting the following technical scheme:

the preparation method takes diphenyl ether and acetone as reaction raw materials, and takes concentrated sulfuric acid, polyphosphoric acid, methanesulfonic acid, trifluoromethanesulfonic acid and the like as acid catalysts to prepare and produce the 9, 9-dimethylxanthene.

According to a preferred embodiment, the reaction scheme of the preparation process according to the invention is as follows:

adding diphenyl ether, acetone and an acid catalyst into a three-neck flask provided with a stirrer and a thermometer, heating for reaction, cooling to room temperature, pouring into ice water, adding a sodium hydroxide aqueous solution into a reaction system, and adjusting the pH to be neutral under stirring. Extracting, drying the organic layer and then carrying out rotary evaporation to obtain a crude product. And recrystallizing to obtain the high-purity product.

According to a preferred embodiment, the molar ratio of diphenyl ether, acetone and acid catalyst according to the invention is 1: 1: 2 to 5.

According to a preferred embodiment, the reaction temperature is 80-120 ℃.

According to a preferred embodiment, the reaction time is 2-5 h.

According to a preferred embodiment, the concentration of the aqueous sodium hydroxide solution in the preparation method is 20-50%. The purpose of adding sodium hydroxide is to neutralize excess acid, reduce the solubility of the product in water, and also prevent the problem that when organic acid catalysis is used, the acid is not neutralized, so that the organic acid is extracted into dichloromethane, and the difficulty of post-treatment is increased.

According to a preferred embodiment, the molar ratio of the sodium hydroxide to the acid catalyst in the preparation method is 1: 1-2.

The invention has the following beneficial effects:

the preparation method of 9, 9-dimethyl xanthene provided by the invention takes diphenyl ether and acetone as reaction raw materials, and takes concentrated sulfuric acid, polyphosphoric acid, methanesulfonic acid, trifluoromethanesulfonic acid and the like to catalyze and replace the traditional production method of flammable and explosive substances such as trimethyl aluminum and n-butyllithium, so that the danger of the production operation process and the special requirements of production equipment are greatly reduced, the method has the characteristics of high reaction speed, high production efficiency, cheap and easily available raw materials, and production by a conventional production device, the production cost is greatly reduced, the yield of the product can reach 70% -75% after optimization, and the content is more than 99%. The method can quickly improve the productivity of the 9, 9-dimethylxanthene, fills the market vacancy caused by the insufficient productivity due to the great production difficulty of the old process, and is favorable for popularization and application.

Drawings

FIG. 1 is an HPLC chromatogram of a target product of the present invention.

FIG. 2 is a nuclear magnetic hydrogen spectrum of the target product of the present invention.

FIG. 3 is a nuclear magnetic carbon spectrum of the target product of the present invention.

Detailed Description

In order to make the implementation objects, technical solutions and advantages of the present invention clearer, the following will clearly and completely describe the technical solutions in the implementation of the present invention.

Example 1

And taking a 500ml three-mouth bottle, sequentially adding 150ml of trifluoromethanesulfonic acid and 78g of diphenyl ether, slowly dropwise adding 26g of acetone after the addition is finished, heating to 120 ℃, keeping the temperature for 2 hours, cooling to room temperature, pouring into ice water, and adjusting the pH to be neutral by using sodium hydroxide with the mass percentage concentration of 20%. After standing overnight, a large amount of pale yellow crystals precipitated, which were filtered, the filtrate was extracted with 500ml of dichloromethane and dried over anhydrous sodium sulfate, and the organic layer was rotary evaporated to give 83g of crude product, which was recrystallized from 200ml of a dichloromethane/methanol mixed solvent to give 70.6g of pure product. The yield thereof was found to be 75%.

Example 2

Taking a 2L four-mouth bottle, sequentially adding 50g of acetone and 154g of diphenyl ether, introducing argon for protection after the addition is finished, then slowly dropwise adding 92ml of concentrated sulfuric acid, heating to 80 ℃ after the dropwise addition is finished, and keeping the temperature for 5 hours. And cooling to room temperature after the reaction is finished, pouring reactants into ice water, and adjusting the pH value to be neutral by using sodium hydroxide with the mass percentage concentration of 20%. After standing overnight, the mixture was extracted with 1L of dichloromethane and dried over anhydrous sodium sulfate, the organic layer was evaporated to 150g of crude product, and the crude product was recrystallized from 600ml of dichloromethane/methanol mixed solvent to give 128g of pure product. The yield thereof was found to be 70.7%.

Example 3

And taking a 2L four-mouth bottle, sequentially adding 254g of methanesulfonic acid and 150g of diphenyl ether, introducing argon for protection after the addition is finished, then slowly dropwise adding 50g of acetone, heating to 120 ℃, and preserving heat for 5 hours after the dropwise addition is finished. And cooling to room temperature after the reaction is finished, pouring the reactant into ice water, and adjusting the pH value to be neutral by using sodium hydroxide with the mass percentage concentration of 30%. After standing overnight, the mixture was extracted with 1L of dichloromethane and dried over anhydrous sodium sulfate, the organic layer was evaporated to give 157g of crude product, which was recrystallized from 600ml of a dichloromethane/methanol mixed solvent to give 135g of pure product. The yield thereof was found to be 74.6%.

Example 4

And (3) taking a 500ml four-mouth bottle, sequentially adding 20g of acetone and 60g of diphenyl ether, introducing argon for protection after the addition is finished, then slowly adding 254g of polyphosphoric acid, heating to 95 ℃ after the dripping is finished, and keeping the temperature for 5 hours. And cooling to room temperature after the reaction is finished, pouring the reactant into ice water, and adjusting the pH value to be neutral by using 25% sodium hydroxide in percentage by mass. After standing overnight, the mixture was extracted with 1L of dichloromethane and dried over anhydrous sodium sulfate, the organic layer was rotary evaporated to give 58g of crude product, which was recrystallized from 200ml of a dichloromethane/methanol mixed solvent to give 51g of pure product. The yield thereof was found to be 70.4%.

The data are characterized as follows:

the HPLC data are shown in FIG. 1.

FIG. 1 shows that the content of the 9, 9-dimethylxanthene obtained by recrystallization in the above example 1 is more than 99% by high performance liquid chromatography.

The NMR spectrum and the carbon spectrum are shown in FIGS. 2 and 3.

FIGS. 2 and 3 showThe nmr spectrum of the product 9, 9-dimethylxanthene obtained in example 1 of the present invention can be obtained from spectrum 2, and the measured value of the hydrogen spectrum is:¹HNMR(DCCl₃,)，:7.43(d,2H,Ar-H)；:7.21(d,2H,Ar-H)；:7.08(m,4H,Ar-H)；:1.65(s,6H,-CH₃) And the spectrogram shows that the analysis result of the number, displacement and fission of hydrogen is consistent with the product structure. From the spectrogram 3, the analysis results of the amount and displacement of carbon are consistent with the product structure, and the product structure is determined to be correct by the analysis results of the hydrogen spectrum and the carbon spectrum.

The above-described examples are intended to be illustrative of some, but not all embodiments of the invention. The detailed description of the embodiments of the present invention is not intended to limit the scope of the invention as claimed, but is merely representative of selected embodiments of the invention. Based on the embodiments of the present invention, other embodiments without creative efforts are within the protection scope of the present invention for those of ordinary skill in the art.

Claims

1. A preparation method of 9, 9-dimethylxanthene is characterized by comprising the following steps: diphenyl ether and acetone are used as raw materials, inorganic or organic acid is used as a catalyst, heating reaction is carried out, cooling to room temperature is carried out after the reaction is finished, the reaction system is poured into ice water, sodium hydroxide aqueous solution is added into the reaction system, and the pH value is adjusted to be neutral under stirring; extracting, drying an organic layer, performing rotary evaporation to obtain a crude product, and recrystallizing to obtain a target product;

the catalyst is concentrated sulfuric acid, polyphosphoric acid, methanesulfonic acid or trifluoromethanesulfonic acid.

2. The method according to claim 1, wherein the molar ratio of the diphenyl ether to the acetone to the catalyst is: 1: 1: 2 to 5.

3. The method according to claim 1, wherein the reaction temperature is 80 to 120 ℃.

4. The process for producing 9, 9-dimethylxanthene according to claim 1, wherein the extracting agent is selected from dichloromethane; a dichloromethane/methanol solution with a volume ratio of 1:1 is used for recrystallization.