CN108238879A - The synthetic method of Vitwas E pharmaceutical intermediate 2,3,5- trimethylbenzoquinones - Google Patents
The synthetic method of Vitwas E pharmaceutical intermediate 2,3,5- trimethylbenzoquinones Download PDFInfo
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- CN108238879A CN108238879A CN201710457002.7A CN201710457002A CN108238879A CN 108238879 A CN108238879 A CN 108238879A CN 201710457002 A CN201710457002 A CN 201710457002A CN 108238879 A CN108238879 A CN 108238879A
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- trimethylbenzoquinoe
- vitwas
- synthetic method
- pharmaceutical intermediate
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C46/00—Preparation of quinones
- C07C46/02—Preparation of quinones by oxidation giving rise to quinoid structures
- C07C46/06—Preparation of quinones by oxidation giving rise to quinoid structures of at least one hydroxy group on a six-membered aromatic ring
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- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses the synthetic methods of 2,3,5 trimethylbenzoquinone of Vitwas E pharmaceutical intermediate, include the following steps：2 methyl, 4 hydroxyl, 3,6 dihydroxymethyl toluene, 2,5 hexylene glycol solution are added in reaction vessel, stirring increases solution temperature, adds in molybdenum disulfide powder, increases solution temperature, keeps 90 140min；Multiple with the extraction of N methylanilines solution, the washing of 2 picoline solutions is multiple, and stratification recrystallizes in 3 methyl, 2 butanol solution, and dehydrating agent dehydration obtains 2,3,5 trimethylbenzoquinone of finished product.
Description
Technical field
The present invention relates to a kind of preparation methods of medicine intermediate, belong to organic synthesis field more particularly to vitamin E vinegar
The synthetic method of acid esters pharmaceutical intermediate 2,3,5- trimethylbenzoquinones.
Background technology
2,3,5-trimethylbenzoquinoe is mainly as the intermediate of Vitwas E, and vitamin E is in body metabolism mistake
Cheng Zhongyou prevents the readily oxidizable substances such as cell membrane and intracellular unrighted acid from being aoxidized, so as to protect the complete of cell membrane and then
The effect of aging is prevented, vitamin E has stronger reproducibility, can be used as antioxidant.For internal antioxidant, eliminate in vivo certainly
By base, injury of the ultraviolet light to human body is reduced.Due to skin care, hair care etc..2,3,5- trimethylbenzoquinones are mainly as vitamin E vinegar
The pharmaceutical intermediate of acid esters, synthetic method quality are of great significance.Existing synthetic method uses 1,2,4- trimethylbenzenes mostly
With concentrated acid sulfonation, generate 2,4,5- tri-methyl p-toluenesulfonates, then nitrified with potassium nitrate and the concentrated sulfuric acid, obtain 2,4,5- trimethyls-
3,6- dinitric acid benzene sulfonic acid potassium, the latter restore to obtain 2,3,5- trimethyl p-phenylenediamine two hydrochloric acid salts, and then with sulfuric acid and dichromic acid
The product are made in sodium oxidation.But this synthetic method is needed using the concentrated sulfuric acid and sodium dichromate as reactant, operating process danger
Dangerous coefficient is higher, and the concentrated sulfuric acid and sodium dichromate environmental pollution are larger, and environmental-friendly coefficient is relatively low, and synthesis technology is more multiple
It is miscellaneous, it is therefore necessary to propose a kind of new synthetic method.
Invention content
Technical problems based on background technology, the present invention propose Vitwas E pharmaceutical intermediate 2,3,5-
The synthetic method of trimethylbenzoquinone, includes the following steps：
A, 2- methyl -4- hydroxyl -3,6- dihydroxymethyl toluene, 2,5- hexylene glycol solution, control are added in reaction vessel
Mixing speed 190-230rpm, raising solution temperature add in molybdenum disulfide powder, raising solution temperature to 48-54 to 40-46 DEG C
DEG C, keep 90-140min；
B, extracted with methylphenylamine solution multiple, the washing of 2- picoline solutions is multiple, stratification, 3- methyl-
It is recrystallized in 2- butanol solutions, dehydrating agent dehydration obtains finished product 2,3,5-trimethylbenzoquinoe.
Preferably, 2,5- hexylene glycols liquid quality fraction is 60-75%.
Preferably, methylphenylamine liquid quality fraction is 80-86%.
Preferably, 2- picoline solutions mass fraction is 85-89%.
Preferably, 3- methyl -2- butanol solutions mass fraction is 91-95%.
Preferably, dehydrating agent is any one in Anhydrous potassium carbonate, phosphorus pentoxide.
Entire reaction process can be represented with following reaction formula：
Compared to synthetic method disclosed in background technology, Vitwas E pharmaceutical intermediate 2,3 provided by the invention,
The synthetic method of 5- trimethylbenzoquinones, this synthetic method do not need to avoid as reactant using the concentrated sulfuric acid and sodium dichromate
The concentrated sulfuric acid and sodium dichromate environmental pollution are larger, and operating process danger coefficient is relatively low, environmental-friendly coefficient is relatively low, in reaction
Between link reduce very much, the reaction time also shortens much, and reaction yield also improves, while the present invention provides a kind of new
Synthetic route is laid a good foundation further to promote reaction yield.
Description of the drawings
Fig. 1 is the infrared analysis spectrogram of finished product 2,3,5- trimethylbenzoquinones.
Specific embodiment
Embodiment 1：
The synthetic method of Vitwas E pharmaceutical intermediate 2,3,5-trimethylbenzoquinoe, includes the following steps：
A, 2- methyl -4- hydroxyl -3,6- dihydroxymethyl toluene of 2mol is added in reaction vessel, 3mol mass fractions are
60% 2,5- hexylene glycol solution, controls mixing speed 190rpm, and raising solution temperature adds in the molybdenum disulfide of 2mol to 40 DEG C
Powder, raising solution temperature keep 90min to 48 DEG C；
B, it is extracted 3 times with the methylphenylamine solution that mass fraction is 80%, mass fraction is 85% 2- picolines
Solution washs 5 times, stratification, is recrystallized in the 3- methyl -2- butanol solutions for being 91% in mass fraction, Anhydrous potassium carbonate takes off
Aqua is dehydrated, and obtains finished product 2,3,5-trimethylbenzoquinoe 523.32g, yield 89%.
Embodiment 2：
The synthetic method of Vitwas E pharmaceutical intermediate 2,3,5-trimethylbenzoquinoe, includes the following steps：
A, 2- methyl -4- hydroxyl -3,6- dihydroxymethyl toluene of 2mol, 3.5mol mass fractions are added in reaction vessel
For 68% 2,5- hexylene glycol solution, mixing speed 210rpm is controlled, raising solution temperature adds in molybdenum disulphide powder to 43 DEG C
End, raising solution temperature keep 120min to 52 DEG C；
B, it is extracted 5 times with the methylphenylamine solution that mass fraction is 83%, mass fraction is 87% 2- picolines
Solution washs 6 times, stratification, is recrystallized in the 3- methyl -2- butanol solutions for being 93% in mass fraction, phosphorus pentoxide takes off
Aqua is dehydrated, and obtains finished product 2,3,5-trimethylbenzoquinoe 535.08g, yield 91%.
Embodiment 3：
The synthetic method of Vitwas E pharmaceutical intermediate 2,3,5-trimethylbenzoquinoe, includes the following steps：
A, 2- methyl -4- hydroxyl -3,6- dihydroxymethyl toluene of 2mol is added in reaction vessel, 4mol mass fractions are
75% 2,5- hexylene glycol solution, controls mixing speed 230rpm, and raising solution temperature adds in the molybdenum disulfide of 3mol to 46 DEG C
Powder, raising solution temperature keep 140min to 54 DEG C；
B, it is extracted 7 times with the methylphenylamine solution that mass fraction is 86%, mass fraction is 89% 2- picolines
Solution washs 9 times, stratification, is recrystallized in the 3- methyl -2- butanol solutions for being 95% in mass fraction, Anhydrous potassium carbonate takes off
Aqua is dehydrated, and obtains finished product 2,3,5-trimethylbenzoquinoe 558.6g, yield 95%.
Infrared analysis is made to finished product 2,3,5-trimethylbenzoquinoe, obtains infrared analysis spectrogram, as shown in Figure 1.
Infrared spectrum data are as shown in table 1.
1 infrared spectrum data of table
It described in above example, is merely preferred embodiments of the present invention, but protection scope of the present invention not office
Be limited to this, any one skilled in the art in the technical scope disclosed by the present invention, the technique according to the invention
Scheme and its inventive concept are subject to equivalent substitution or change, should be covered by the protection scope of the present invention.
Claims (7)
1. the synthetic method of Vitwas E pharmaceutical intermediate 2,3,5-trimethylbenzoquinoe, which is characterized in that including walking as follows
Suddenly：
A, 2- methyl -4- hydroxyl -3,6- dihydroxymethyl toluene, 2,5- hexylene glycol solution, control stirring are added in reaction vessel
Speed 190-230rpm, raising solution temperature add in molybdenum disulfide powder to 40-46 DEG C, increase solution temperature to 48-54 DEG C,
Keep 90-140min；
B, it is extracted repeatedly with methylphenylamine solution, the washing of 2- picoline solutions is multiple, stratification, in 3- methyl -2- fourths
It is recrystallized in alcoholic solution, dehydrating agent dehydration obtains finished product 2,3,5-trimethylbenzoquinoe.
2. the synthetic method of Vitwas E pharmaceutical intermediate 2,3,5-trimethylbenzoquinoe according to claim 1, special
Sign is that 2, the 5- hexylene glycols liquid quality fraction is 60-75%.
3. the synthetic method of Vitwas E pharmaceutical intermediate 2,3,5-trimethylbenzoquinoe according to claim 1, special
Sign is that the methylphenylamine liquid quality fraction is 80-86%.
4. the synthetic method of Vitwas E pharmaceutical intermediate 2,3,5-trimethylbenzoquinoe according to claim 1, special
Sign is that the 2- picoline solutions mass fraction is 85-89%.
5. the synthetic method of Vitwas E pharmaceutical intermediate 2,3,5-trimethylbenzoquinoe according to claim 1, special
Sign is that the 3- methyl -2- butanol solutions mass fraction is 91-95%.
6. the synthetic method of Vitwas E pharmaceutical intermediate 2,3,5-trimethylbenzoquinoe according to claim 1, special
Sign is that the dehydrating agent is any one in Anhydrous potassium carbonate, phosphorus pentoxide.
7. the synthetic method of Vitwas E pharmaceutical intermediate 2,3,5-trimethylbenzoquinoe according to claim 1, special
Sign is, includes the following steps：
A, 2- methyl -4- hydroxyl -3,6- dihydroxymethyl toluene of 2mol is added in reaction vessel, 4mol mass fractions are 75%
2,5- hexylene glycol solution, control mixing speed 230rpm, raising solution temperature to 46 DEG C, add in the molybdenum disulphide powder of 3mol
End, raising solution temperature keep 140min to 54 DEG C；
B, it is extracted 7 times with the methylphenylamine solution that mass fraction is 86%, mass fraction is 89% 2- picoline solutions
Washing 9 times, stratification recrystallize, Anhydrous potassium carbonate dehydrating agent in 3- methyl -2- butanol solutions of the mass fraction for 95%
Dehydration, obtains finished product 2,3,5-trimethylbenzoquinoe.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710457002.7A CN108238879A (en) | 2017-06-16 | 2017-06-16 | The synthetic method of Vitwas E pharmaceutical intermediate 2,3,5- trimethylbenzoquinones |
| GBGB1709973.0A GB201709973D0 (en) | 2017-06-16 | 2017-06-22 | Vitamin E acetate intermediates 2,3,5-trimethylbdnzoquinine synthesis method |
| IES20180121A IES87022B2 (en) | 2017-06-16 | 2018-04-04 | Vitamin E acetate intermediates 2,3,5-trimethylbenzoquinone synthesis method |
| AU2018100523A AU2018100523A4 (en) | 2017-06-16 | 2018-04-24 | Vitamin E acetate intermediates 2,3,5-trimethylbenzoquinone synthesis method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710457002.7A CN108238879A (en) | 2017-06-16 | 2017-06-16 | The synthetic method of Vitwas E pharmaceutical intermediate 2,3,5- trimethylbenzoquinones |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108238879A true CN108238879A (en) | 2018-07-03 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710457002.7A Pending CN108238879A (en) | 2017-06-16 | 2017-06-16 | The synthetic method of Vitwas E pharmaceutical intermediate 2,3,5- trimethylbenzoquinones |
Country Status (4)
| Country | Link |
|---|---|
| CN (1) | CN108238879A (en) |
| AU (1) | AU2018100523A4 (en) |
| GB (1) | GB201709973D0 (en) |
| IE (1) | IES87022B2 (en) |
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2017
- 2017-06-16 CN CN201710457002.7A patent/CN108238879A/en active Pending
- 2017-06-22 GB GBGB1709973.0A patent/GB201709973D0/en not_active Ceased
-
2018
- 2018-04-04 IE IES20180121A patent/IES87022B2/en unknown
- 2018-04-24 AU AU2018100523A patent/AU2018100523A4/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| IES20180121A2 (en) | 2019-06-12 |
| IES87022B2 (en) | 2019-06-12 |
| GB201709973D0 (en) | 2017-08-09 |
| AU2018100523A4 (en) | 2018-05-24 |
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Application publication date: 20180703 |