IES20180121A2

IES20180121A2 - Vitamin E acetate intermediates 2,3,5-trimethylbenzoquinone synthesis method

Info

Publication number: IES20180121A2
Application number: IES20180121A
Authority: IE
Inventors: Peng Fei
Original assignee: Chengdu Qie Si Te Tech Co Ltd
Priority date: 2017-06-16
Filing date: 2018-04-04
Publication date: 2019-06-12
Also published as: GB201709973D0; IES87022B2; AU2018100523A4; CN108238879A

Abstract

The present invention discloses vitamin E acetate intermediates 2,3,5-trimethylbenzoquinone synthesis method by 2-methyl-4-hydroxy-3,6-dimethylol toluene, 2,5-hexanediol solution were added to the reaction vessel, controlled the stirring speed, raising the solution temperature, added molybdenum disulfide powder, raised the temperature of the solution, kept for 90-140 min; extracted with N-methylaniline solution for several times, washed with 2-methylpyridine solution for several times, standing for stratification, recrystallized in 3-methyl-2-butanol solution, dehydrated with dehydrating agent, finally got finished product 2, 3,5 -trimethyl benzoquinone.

Description

Vitamin E acetate intermediates 2,3,5—ti'imethylbenzoquinone synthesis method FIELD OF THE INVENTION The present invention relates to a method for preparing a pharmaceutical intermediate which belongs to the field of organic synthesis, more particularly, relates to vitamin E acetate intermediates 2,3,5—trimethylbenzoquinone synthesis method.

GENERAL BACKGROUND Vitamin E acetate plays a role of preventing the cell membrane and intracellular unsaturated fatty acids and other antioxidants oxidized in metabolic process of the body, so as to protect the integrity of the cell membrane and thus prevent aging in the body. Vitamin E has a strong reduction, it can be used as antioxidants, eliminating free radicals in the body, reducing the damage to the human body. It can be used for skin care, hair care and so on. As a pharmaceutical intermediates of vitamin E acetate, the synthesis method of 2,3,5-trimethylbenzoquinone is ofgreat signiﬁcance. Most of the existing synthetic methods are using the method that I,2,4-trimethylbenzene sulfonated with concentrated sulfuric acid to produce 2,4,5—trimethylbenzenesulfonic acid, and then nitrated with potassium nitrate and concentrated sulfuric acid to produce 2,4,5—trimethyl—3,6-dinitrate benzenesulfonic acid potassium, the latter is restored to 2,3,5-trimethyl—p-phenylenediamine dihydrochloride, and then obtained the products that oxidated by sulfuric acid and sodium dichromate. However, this method requires concentrated sulfuric acid and sodium dichromate as reactants, the operation process is very dangerous, environment—friendly coefﬁcient of using concentrated sulfuric acid and sodium dichromate is low, and the synthesis process is more complex. Therefore, it is necessary to propose anew synthetic method.

SUMMARY Based on the technical problems of the background technology, the purpose of the present invention is to provide vitamin E acetate intermediates 2,3.5-trimethylbenzoquinone synthesis method, comprises the following steps: A: 2-methyl—4—hydroxy-3,6-dimethylol toluene, 2,5-hexanediol solution were added to the reaction vessel, controlled the stirring speed at l90~23O rpm, raising the solution temperature to 40-46 "C, added molybdenum disulfide powder, raised the temperature of the solution to 48~54 "C, kept for 90-140 min; B: extracted with N—methylaniline solution for several times, washed with 2-methylpyridine solution for several times, standing for stratification, recrystallized in 3—methyl-2~butanol solution, dehydrated with dehydrating agent, ﬁnally got finished product 2, 3,5-trimethylbenzoquinone.

Preferably, the 2,5~hexanediol solution has a mass fraction of 60-75%.

Preferably, the mass fraction of the N-methylaniline solution is 80-86%.

Preferably, the 2-methylpyridine solution has a mass fraction of 85-89%.

Preferably, the 3-methyl-2—butanol solution has a mass fraction of 91-95%.

Preferably, the dehydrating agent is any one of anhydrous potassium carbonate and phosphorus pentoxide.

Throughout the reaction process can be the following reaction formula: CH: O H0H2C CH3 H30 CH3 ' Q.‘ ‘:40: ' MUS: ----—-b CHZOH CH3 OH 0 Compared with the synthetic method disclosed in the background art, the invention provides vitamin E acetate intermediates 2,3,5-trimethylbenzoquinone synthesis method, this synthesis method use without concentrated sulfuric acid and sodium dichromate as reactants, the risk coefficient of operation is low, the environment~ﬁriendly coelficieiit is low, avoiding the environmental pollution, reducing intermediate links reaction, decreasing the reaction time and improving the reaction yield, at the same time, the present invention provides a new synthetic route which has laid a good foundation for further enhancing the yield of the reaction.

DESCRIPTION OF THE DRAWINGS Figure l is the infrared analysis spectrum of ﬁnished product 2, 3,5—trimethylbenzoquinone.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS The following examples with reference to speciﬁc embodiments of the present invention are ﬁirther illustrated: Embodiment 1 Vitamin E acetate intermediates 2,3,5-trimethylbenzoquinone synthesis method, comprises the following steps: A: 2 mol 2—methyl—4-hydroxy-3,6-dimethylol toluene, 3mol 2,5-hexanediol solution with a mass fraction of 60% was added to the reaction vessel, controlled the stirring speed at 190 rpm, raising the solution temperature to 40 °C, added 2 mol molybdenum disulﬁde powder, raised the temperature of the solution to 48 "C, kept for 90 min; B: extracted with N-methylaniline solution with a mass fraction of 80% for 3 times, washed with 2—methylpyricline solution with a mass fraction of 85% for 5 times, standing for stratification, recrystallized in 3-methyl~2-butanol solution with a mass fraction of 9l%, dehydrated with potassium carbonate dehydrating agent, finally got finished product 2, 3,5-trimethylbenzoquinone 523.32g, yield of 89%.

Embodiment 2 Vitamin E acetate intermediates 2,3,5~trimethylbenzoquinone synthesis method, comprises the following steps: A: 2 mol 2—methyl~4~hydroxy-3,6-dimethylol toluene, 3.5mol 2,5-hexanediol solution with a mass fraction of 68% was added to the reaction vessel, controlled the stirring speed at 210 rpm, raising the solution temperature to 43 "C, added 2 mol molybdenum disulfide powder, raised the temperature of the solution to 52 “C, kept for 120 min; B: extracted with N~methylaniline solution with a mass fraction of 83%_ for 5 times, washed with 2—methylpyridine solution with a mass fraction of 87% for 6 times, standing for stratification, recrystallized in 3-methyl~2—butanol solution with a mass fraction of 93%, dehydrated with phosphorus pentoxide dehydrating agent, ﬁnally got finished product 2, 3,5-trimethylbenzoquinone 535.08g, yield of‘9l%.

Embodiment 3 Vitamin E acetate intermediates 2,3,5-trimethylbenzoquinone synthesis method, comprises the following steps: A: 2 mol 2~methyl-4—hydroxy-3,6-dimethylol toluene, 4mol 2,5—hexanediol solution with a mass fraction of 75% was added to the reaction vessel, controlled the stirring speed at 230 rpm, raising the solution temperature to 46 °C, added 3 mol molybdenum disulﬁde powder, raised the temperature of the solution to 54 "C, kept for 140 min; B: extracted with N-methylaniline solution with a mass fraction of 86% for 7 times, washed with 2-methylpyridine solution with a mass fraction of 89% for 9 times, standing for stratification, recrystallized in 3-methyl-2—butanol solution with a mass fraction of 95%, dehydrated with potassium carbonate dehydrating agent, finally got ﬁnished product 2, 3,5—trimethylbenzoquinone 558.6g, yield of 95%.

Infrared analysis of finished product 2, 3,5—trimethylbenzoquinone, infrared spectrum shown in figure I, the analysis of data as shown in Table 1: Table 1: Peak data Serial Peak position Transmittance Half width Peak difference number (cm") (°/o) (cm") (%) l l253 48 41 34 2 131 l 48 34 33 3 1384 59 32 26 4 i666 9 52 84 293 6 66 3 8 24 The embodiments of the present invention are merely preferred embodiments of the present invention, but the range of the present invention is not limited this, and any person who is familiar with those skilled in the arts, within the technical range of the present invention. It is intended that the technical solution and its inventive concept be replaced or modified equivalently with reference to the range of the invention.

Claims

1. I. Vitamin E acetate intermediates 2.3,5~trimethylbenzoquinone synthesis method, comprises the following steps: A: 2~methyl—4-hydroxy-3,6—dimethylol toluene, 2,5—hexanediol solution were added to the reaction vessel, controlled the stirring speed at l90~230 rpm, raising the solution temperature to 40-46 "C, added molybdenum disulﬁde powder, raised the temperature of the solution to 48-54 "C , kept for 90-140 min; B: extracted with N-methylaniline solution for several times, washed with 2—methylpyridine solution for several times, standing for stratification, recrystallized in 3~methyl—2-butanol solution, dehydrated with dehydrating agent, ﬁnally got finished product 2, 3,5-trimethylbenzoquinone.

2. Vitamin E acetate intermediates 2,3,5-trimethylbenzoquinone synthesis method according to claim I wherein the 2,5~hexanediol solution has a mass fraction 0560-75%.

3. Vitamin E acetate intermediates 2,3,5—trimethylbenzoquinone synthesis method according to claim I wherein the mass fraction of the N-methylaniline solution is 80-86%..

4. Vitamin E acetate intermediates 2,3,5—trimethylbenzoquinone synthesis method according to claim 1 wherein the 2—methylpyridine solution has a mass fraction of 85-89%.