CN100999445A - Demethyl method of aryl methyl ether - Google Patents
Demethyl method of aryl methyl ether Download PDFInfo
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- CN100999445A CN100999445A CN 200610000648 CN200610000648A CN100999445A CN 100999445 A CN100999445 A CN 100999445A CN 200610000648 CN200610000648 CN 200610000648 CN 200610000648 A CN200610000648 A CN 200610000648A CN 100999445 A CN100999445 A CN 100999445A
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- thioether
- lewis acid
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Abstract
This invention involves a method of aryl methyl ether demethylation. It has the following reaction formula: R - (O-CH3) n ---> R - (OH) n; the R is substitute or not substitute aromatic group, such as: phenyl, cresyl, xylyl and the styryl; n represent integer of 1-3. The reaction steps: first, aryl-methyl ether and a Lewis acid placed in inert solvents, stirring under low temperature, slowly adding 1-2 times Lewis acid equivalent thio ether to the mixture, control of the reaction temperature at10 degrees below, then placed to room temperature; second, add the above reaction slowly to the strong mixing ice water, then extracting the mixture with ethyl acetate, washing, concentrating and dry, and gain corresponding phenol.
Description
Technical field:
The present invention relates to a kind of chemical synthesis process, particularly a kind of aryl methyl ether is carried out demethylation, obtain the method for aryl cresols.
Background technology:
Aryl methyl ether is a big class chemical substance, and structural formula is as follows:
R-O-CH
3
R is for replacing or unsubstituted aryl group
Wherein useful compound such as methyl-phenoxide, p-tolyl methyl ether, o-tolyl methyl ether, m-tolyl methyl ether, 3, the 5-dimethoxy-p, 3,5,4 '-the trimethoxy toluylene etc., can obtain the another kind of useful following compound of structural formula, aryl cresols from this compounds through demethylation
R-OH
R is for replacing or unsubstituted aryl group
Demethylation for aryl methyl ether obtains aryl cresols method, and bibliographical information is many at present.Mainly contain
As J.Org.Chem, the Iodotrimethylsilane method described in 42,3761 (1977), Org.Synth., Collect.Vol.V, the boron tribromide method described in 412 (1973), the subject matter that these two methods exist are that the cost of demethylation is too high;
J.Am.Chem.Soc., the pyridine hydrochloride method described in 78,1380 (1956), the main drawback of this method is that the productive rate of demethylation is on the low side;
J.O.Chem., the aluminum chloride-mercaptans described in 45,4275 (1980),
This method application limitation is arranged, be not suitable for the aryl methyl ether that contains two keys in the structure.
Above-described method exists that reaction yield is low, reaction cost is high or the little shortcoming of the reaction scope of application.Therefore, press for the demethyl method of a kind of new aryl methyl ether of exploitation, this method must satisfy the characteristics that cost is low, yield is high, use range is wide simultaneously.The solution of success of the present invention the problems referred to above, the demethyl method of the aryl methyl ether that a kind of cost is low, yield is high, use range is wide is provided.
Summary of the invention:
The invention provides the method that a kind of aryl methyl ether process demethylation obtains aryl cresols, described aryl cresols structure is as follows
R-(OH)n
Wherein R is replacement or unsubstituted aryl group, as: phenyl, tolyl, xylyl, diphenylethyllene
N represents the integer of 1-3
-(OH) in any position of phenyl, as 1, ortho position, a position, contraposition.
Preparation method of the present invention has following reaction formula
R-(O-CH
3)n→R-(OH)n
R and n represent the same.
Method of the present invention, the process following steps:
The first step places inert solvent with aryl methyl ether and a kind of Lewis acid, and low temperature stirs down, slowly drips the 1-2 times of normal thioether of Lewis acid, control reaction temperature below 10 ℃ in mixed solution, after dripping off, is placed to room temperature;
Second step slowly added above-mentioned reactant in the intensively stirred frozen water, mixture with ethyl acetate extraction, through washing, concentrate, drying, obtain corresponding phenol.
In the above step,
Described inert solvent is selected from: methylene dichloride, chloroform, tetracol phenixin, ethylene dichloride.Preferably: methylene dichloride
Described aryl methyl ether is selected from: 3,5,4 '-the trimethoxy toluylene, 3,5-dimethoxy-p, methyl-phenoxide.Preferably: 3,5,4 '-the trimethoxy toluylene
Described Lewis acid is selected from: aluminum chloride, alchlor, boron trifluoride, boron tribromide.Preferably: aluminum chloride
Described thioether is selected from: dimethyl sulphide, methylethyl thioether, diethyl thioether, thioanisole.Preferably:
Dimethyl sulphide
The amount of thioether 1-1.5 times of normal thioether of Lewis acid preferably wherein, most preferred is 1.1 times of equivalents.
Wherein aryl monomethyl ether and lewis acidic ratio are 1: 1～1: 2, and most preferred is 1: 1.1, and wherein the many methyl ethers of aryl are converted to the aryl monomethyl ether, are equivalent to 2 moles of aryl monomethyl ethers as 1 mole of aryl dme.
Above method is compared with prior art, and advantage is that reaction conditions relaxes, and the solvent of use is in extensive range, simple to operate, the productive rate height, the purity height, cost is low, be fit to scale operation,, have good practical value particularly at important compounds such as orcinols.
Embodiment:
Further specify the present invention by the following examples, but not as limitation of the present invention.
Embodiment 1
Synthesizing of orcinol
In a there-necked flask that thermometer, agitator and constant pressure funnel be housed, add 8.5g3,5-dimethoxy-p, 25mL methylene dichloride and 27g aluminum trichloride (anhydrous).When stirring, solution is cooled to 0 ℃, in 0.5 hour, adds the 4mL dimethyl thioether.The temperature of reaction mixture remains on 8～11 ℃; Stirred 1 hour.Stop cooling, and make the temperature of reaction mixture in 45 minutes, be elevated to 25 ℃.Suspension was stirred 4 hours at 25 ℃.After 4 hours, in suspension impouring 50mL water, add dilute hydrochloric acid and transfer pH to 4～5.Ethyl acetate extraction (25mL * 3) merges organic layer; Washing, dry, concentrated.A spot of water of adding and gac add heat decoloring in the resistates, filter, cool off.Extracted with diethyl ether obtains the crystallization of 5.4g light red, productive rate 77.9% behind the evaporate to dryness; Mp106～108 ℃.
Embodiment 2
Add the 20mL methylene dichloride in the 100mL there-necked flask, be cooled to 0 ℃, add the 6g aluminum trichloride (anhydrous), stir 15min; Slowly drip the 10mL dimethyl sulphide, controlled temperature is no more than 20 ℃.Add 2.16g 3,5,4 '-trimethoxy toluylene, stirring at room 3h.Add the 100g frozen water in the 250mL flask, above-mentioned material is slowly added, stir 0.5h.Add 10% hydrochloric acid to clarification, ethyl acetate extraction (40mL * 4), saturated NaCl is washed till neutrality.Dry.Revolve to steam and obtain crude product.Obtain the light yellow crystallization of 1.54g after the recrystallizing methanol, productive rate 85%; Mp263～267 ℃.
Embodiment 3
Synthesizing of resorcin(ol)
In a there-necked flask that thermometer, agitator and constant pressure funnel be housed, add 10g1,3-dimethoxy benzene, 28mL methylene dichloride and 30g aluminum trichloride (anhydrous).When stirring, solution is cooled to 0 ℃, in 0.5 hour, adds the 4.5mL dimethyl thioether.The temperature of reaction mixture remains on 8～11 ℃; Stirred 1 hour.Stop cooling, and make the temperature of reaction mixture in 60 minutes, be elevated to 25 ℃.Suspension was stirred 4 hours at 25 ℃.After 4 hours, in suspension impouring 50mL water, add dilute hydrochloric acid and transfer pH to 4～5.Ethyl acetate extraction (20mL * 4) merges organic layer; Washing, dry, concentrated.A spot of water of adding and gac add heat decoloring in the resistates, filter, cool off.Extracted with diethyl ether obtains the 6.3g white crystals behind the evaporate to dryness, slow pulverize redness in the air, productive rate 79.1%; Mp111 ℃.
Embodiment 4
1,3,5-trimethylammonium-2,4,6-three (3, the 5-di-tert-butyl-4-hydroxyl benzyl) benzene synthetic
Add the 120mL methylene dichloride in the 500mL there-necked flask, be cooled to 0 ℃, add the 23g aluminum trichloride (anhydrous), stir 15min; Slowly drip the 36mL dimethyl sulphide, controlled temperature is no more than 20 ℃.Add 36g 1,3,5-trimethylammonium-2,4,6-three (3,5-di-t-butyl-4-methoxy-benzyl) benzene, stirring at room 3h.Add the 300g frozen water in the 1000mL flask, above-mentioned material is slowly added, stir 0.5h.Add 10% hydrochloric acid to clarification, ethyl acetate extraction (100mL * 4), saturated NaCl is washed till neutrality.Dry.Revolve to steam and obtain crude product.Obtain the crystallization of 24.2g off-white color after the recrystallizing methanol, productive rate 70.8%; Mp243～244 ℃.
Claims (10)
1, a kind of method for preparing following formula aryl cresols compound,
R-(OH)n
Wherein R is selected from phenyl for replacing or unsubstituted aryl group, tolyl, and xylyl, diphenylethyllene,
N represents the integer of 1-3,
-(OH) any position on phenyl,
It is characterized in that the process following steps:
The first step, the arylmethyl ether compound that structure is following
R-(O-CH
3) n, wherein R and n represent the same,
Place inert solvent with a kind of Lewis acid, low temperature stirs down, slowly drips the 1-2 times of normal thioether of Lewis acid, control reaction temperature below 10 ℃ in mixed solution, after dripping off, is placed to room temperature;
Second step slowly added above-mentioned reactant in the intensively stirred frozen water, mixture with ethyl acetate extraction, through washing, concentrate, drying, obtain corresponding phenol.
2, the described method of claim 1 is characterized in that,
Described inert solvent is selected from: methylene dichloride, chloroform, tetracol phenixin, ethylene dichloride
Described aryl methyl ether is selected from: 3,5,4 '-the trimethoxy toluylene, 3,5-dimethoxy-p, methyl-phenoxide
Described Lewis acid is selected from: aluminum chloride, alchlor, boron trifluoride, boron tribromide
Described thioether is selected from: dimethyl sulphide, methylethyl thioether, diethyl thioether, thioanisole
3, the method for claim 1 is characterized in that,
Described inert solvent is: methylene dichloride
Described aryl methyl ether is: 3,5,4 '-the trimethoxy toluylene
Described Lewis acid is: aluminum chloride
Described thioether is: dimethyl sulphide
4, the method for claim 1 is characterized in that, wherein the normal thioether of the amount 1-1.5 of thioether times Lewis acid.
5, the described method of claim 1 is characterized in that, wherein 1.1 times of normal thioethers of Lewis acid of the amount of thioether.
6, the described method of claim 1 is characterized in that, aryl monomethyl ether and lewis acidic ratio are 1: 1～1: 2.
7, the described method of claim 1 is characterized in that, aryl monomethyl ether and lewis acidic ratio are 1: 1.1.
8, the described method of claim 1 is characterized in that, described aryl cresols is orcinol.
9, the described method of claim 1 is characterized in that, described aryl cresols is 3,5,4 '-the trihydroxy-toluylene.
10, the described method of claim 1 is characterized in that, described aryl cresols is phenol.
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| CNB2006100006484A CN100509728C (en) | 2006-01-09 | 2006-01-09 | Demethyl method of aryl methyl ether |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103058830A (en) * | 2012-12-13 | 2013-04-24 | 大兴安岭林格贝有机食品有限责任公司 | Production technology for extracting orcinol from parmelia saxatilis |
| CN103087027A (en) * | 2013-01-17 | 2013-05-08 | 中国人民解放军第三军医大学军事预防医学院 | Preparation process of polyhydroxy isoflavone |
| CN106317118A (en) * | 2016-08-22 | 2017-01-11 | 河南省法恩莱特新能源科技有限公司 | Synthesis method of hexa(4-hydroxyl oxethyl) cyclotriphosphazene |
| CN106957431A (en) * | 2016-01-11 | 2017-07-18 | 财团法人工业技术研究院 | The preparation method of poly arylidene thio-ester |
| US10287396B2 (en) | 2016-01-11 | 2019-05-14 | Industrial Technology Research Institute | Polymer |
| CN109970513A (en) * | 2019-03-04 | 2019-07-05 | 宝鸡文理学院 | A method of phenol in catalysis recycling methanol method synthesis methyl phenyl ethers anisole technique |
-
2006
- 2006-01-09 CN CNB2006100006484A patent/CN100509728C/en active Active
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103058830A (en) * | 2012-12-13 | 2013-04-24 | 大兴安岭林格贝有机食品有限责任公司 | Production technology for extracting orcinol from parmelia saxatilis |
| CN103058830B (en) * | 2012-12-13 | 2015-09-30 | 大兴安岭林格贝寒带生物科技股份有限公司 | The production technology of orcinol is extracted in a kind of stone plum clothing |
| CN103087027A (en) * | 2013-01-17 | 2013-05-08 | 中国人民解放军第三军医大学军事预防医学院 | Preparation process of polyhydroxy isoflavone |
| CN106957431A (en) * | 2016-01-11 | 2017-07-18 | 财团法人工业技术研究院 | The preparation method of poly arylidene thio-ester |
| US10287396B2 (en) | 2016-01-11 | 2019-05-14 | Industrial Technology Research Institute | Polymer |
| CN106957431B (en) * | 2016-01-11 | 2019-06-07 | 财团法人工业技术研究院 | The preparation method of poly arylidene thio-ester |
| CN106317118A (en) * | 2016-08-22 | 2017-01-11 | 河南省法恩莱特新能源科技有限公司 | Synthesis method of hexa(4-hydroxyl oxethyl) cyclotriphosphazene |
| CN106317118B (en) * | 2016-08-22 | 2018-06-26 | 河南省法恩莱特新能源科技有限公司 | A kind of synthetic method of six (4- hydroxyl-oxethyls) ring, three phosphonitrile |
| CN109970513A (en) * | 2019-03-04 | 2019-07-05 | 宝鸡文理学院 | A method of phenol in catalysis recycling methanol method synthesis methyl phenyl ethers anisole technique |
| CN109970513B (en) * | 2019-03-04 | 2021-12-28 | 宝鸡文理学院 | Method for catalytically recovering phenol in anisole synthesis process by methanol method |
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| CN100509728C (en) | 2009-07-08 |
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Address after: 100021 Beijing city Chaoyang District Jinsong three District No. 302 Huateng building room 1101 Co-patentee after: Zhejiang Second Pharmaceutical Co.,Ltd. Patentee after: China Resources Saike Pharmaceutical Co., Ltd. Address before: 100021 Beijing city Chaoyang District Jinsong three District No. 302 Huateng building room 1101 Co-patentee before: Zhejiang Second Pharmaceutical Co.,Ltd. Patentee before: Saike Pharmaceutical Co., Ltd., Beijing |