CN102675148A - Preparation method of hydroxybenzyl cyanide - Google Patents
Preparation method of hydroxybenzyl cyanide Download PDFInfo
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- CN102675148A CN102675148A CN2012101212662A CN201210121266A CN102675148A CN 102675148 A CN102675148 A CN 102675148A CN 2012101212662 A CN2012101212662 A CN 2012101212662A CN 201210121266 A CN201210121266 A CN 201210121266A CN 102675148 A CN102675148 A CN 102675148A
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- hydroxybenzylcyanide
- preparation
- phydroxybenzeneactamide
- organic solvent
- consumption
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/54—Improvements relating to the production of bulk chemicals using solvents, e.g. supercritical solvents or ionic liquids
Abstract
The invention belongs to the field of organic chemical synthesis and particularly relates to a preparation method of hydroxybenzyl cyanide. The preparation method of the hydroxybenzyl cyanide comprises the following steps: taking P-hydroxyphenylacetamide as a raw material and carrying out dehydration reaction on the P-hydroxyphenylacetamide in an organic solvent under the condition that dibutyltin oxide and an ion liquid compound exist to obtain the hydroxybenzyl cyanide, wherein the organic solvent selects from toluene, ethylbenzene, isopropylbenzene, n-butyl benzene, benzene, nitrobenzene, chlorobenzene and mixture thereof. In the preparation method, the hydroxybenzyl cyanide is prepared through taking the P-hydroxyphenylacetamide as the raw material, the dibutyltin oxide as a dewatering agent, the ion liquid compound as a catalyst, and the toluene and the like as a solvent and a dehydrating agent. The preparation method has the characteristics of mild reaction condition, no pollution and high yield; the dibutyltin oxide and the ion liquid can be recycled for above 10 times, and the yield is basically kept unchanged.
Description
Technical field
The invention belongs to the synthetic field of organic chemistry, more specifically, relate to a kind of preparation method of p-hydroxybenzylcyanide.
Background technology
P-hydroxybenzylcyanide is a kind of important medicine intermediate, is the important source material of synthetic Bextra atenolol USP 23 (having another name called Target), and the domestic and international market demand is big, has good market outlook.
The synthetic route of the p-hydroxybenzylcyanide of having reported at present is less, mainly adopts following three synthetic routes to synthesize:
(1) be that raw material is synthetic with the benzyl cyanide: this technology is raw material with the benzyl cyanide; Be total to four-step reaction through nitrated, reduction, diazotization and hydrolysis and prepare p-hydroxybenzylcyanide (" synthesizing of MS-932 "; " University Of Hebei's journal: natural science edition " the 2nd phase, 2008,178～200.), the four-step reaction total recovery is less than 30%.This reaction process step is many, and dealing with complicated is used two kinds of strong acid of a large amount of vitriol oils and concentrated nitric acid in the reaction process, not only serious to equipment corrosion, and it is high to produce a large amount of three wastes processing costs simultaneously.Along with the innovation of technology, this technology will be eliminated.
(2) being that raw material is synthetic to hydroxyl benzyl chlorine: this technology is with to hydroxyl benzyl chlorine and sodium cyanide or Potssium Cyanide prepared in reaction (Czech Rep.; P2009301063); Use the sodium cyanide or the Potssium Cyanide reagent of severe toxicity in this technology, environmental pollution is serious, will be replaced gradually.
(3) one Chinese patent application CN102180810A is that raw material is synthetic with the phydroxybenzeneactamide: this technology is raw material with the phydroxybenzeneactamide, utilizes thionyl chloride to prepare p-hydroxybenzylcyanide for dewatering agent dewaters.Can produce a large amount of hydrogen chloride emissions in this technology, complex disposal process need activated carbon decolorizing and repeatedly recrystallization get product, purity can reach about 95%.In addition, the inventor is starting raw material with the phydroxybenzeneactamide, adopts aforesaid method to utilize thionyl chloride dehydration preparation p-hydroxybenzylcyanide; By product is more in the reaction; The product colour of preparation is yellow, and productive rate is only about 45%, and the height of the productive rate 95.5% of this patented claim report not.
Summary of the invention
In view of this, the object of the present invention is to provide the preparation method of the p-hydroxybenzylcyanide that a kind of preparation technology is easy, reaction conditions is gentle, cost is low, the product yield is high, to overcome the above-mentioned defective that exists in the prior art.
According to the present invention; The present invention provides a kind of preparation method of p-hydroxybenzylcyanide, and this method comprises: be raw material with the phydroxybenzeneactamide, in organic solvent; In the presence of Dibutyltin oxide and ionic liquefaction compound; Phydroxybenzeneactamide carries out dehydration reaction, obtains p-hydroxybenzylcyanide, and wherein said organic solvent is selected from toluene, ethylbenzene, isopropyl benzene, n-butyl benzene, benzene, YLENE, oil of mirbane, chlorobenzene and its mixture.
Below, preparation method of the present invention is described particularly.
In the present invention, said organic solvent is selected from toluene, ethylbenzene, isopropyl benzene, n-butyl benzene, benzene, YLENE, oil of mirbane, chlorobenzene and its mixture, is preferably toluene, ethylbenzene or isopropyl benzene, and most preferably is toluene.
Said ionic liquefaction compound (hereinafter referred ILs) is for being selected among the ionic liquefaction compound that following structural formula representes:
In said structural formula A and B, R
1Be C
1～C
6Alkyl, X is Cl or Br.In the present invention, said ionic liquefaction compound is preferably following compound, wherein R
1Be preferably C
1～C
3Alkyl, most preferably be methyl or ethyl; X is Cl or Br, is preferably Br.The concrete instance of this ionic liquefaction compound can be bromination N-butyl-pyridinium, bromination N-picoline, bromination 1-methyl-3-ethyl imidazol(e) salt or bromination 1-methyl-3-propyl imidazole salt.
In preparation method of the present invention, in the dehydration reaction of phydroxybenzeneactamide, the mol ratio of Dibutyltin oxide and phydroxybenzeneactamide is 0.01: 1.0～0.15: 1.0, is preferably 0.03: 1.0～0.1: 1.0, most preferably is 0.05: 1.0; The consumption of said organic solvent is to make that this consumption of organic solvent is 5～50 times of phydroxybenzeneactamide consumption, most preferably is 30 times, by weight; The consumption of said ionic liquefaction compound is to make that this ionic liquid compound amount is 0.5～10% of a phydroxybenzeneactamide consumption, most preferably is 2%, by weight.
In the dehydration reaction of phydroxybenzeneactamide, under the temperature in the reflux temperature-30 of said organic solvent ℃ to the reflow temperature range of said organic solvent, and preferred under the reflux temperature of organic solvent stirring reaction 15～20h; Adopt TLC detection reaction process (developping agent petrol ether/ethyl acetate (volume ratio 2: 1), the R of p-hydroxybenzylcyanide
fAbout=0.6); After reaction finished, filtered while hot was removed Dibutyltin oxide and ionic liquefaction compound, and filtrating is carried out crystallisation by cooling, crossed and filtered pure white product p-hydroxybenzylcyanide.
When being solvent with toluene, in the presence of Dibutyltin oxide and ionic liquefaction compound, phydroxybenzeneactamide carries out dehydration reaction, and this reaction formula is following:
In sum, the present invention has following advantage:
In the present invention is raw material with the phydroxybenzeneactamide, and Dibutyltin oxide is a dewatering agent, and the ionic liquefaction compound is a catalyzer, and toluene etc. have reaction conditions gentleness, pollution-free and characteristics that productive rate is high for solvent and band aqua prepare p-hydroxybenzylcyanide; Dibutyltin oxide and ionic liquid can recycle more than 10 times, and yield remains unchanged basically.
Therefore; The preparation method of p-hydroxybenzylcyanide of the present invention, it is short, easy and simple to handle, pollution-free that this technological line has route, and dewatering agent and catalyzer can recycle; Being easy to the characteristics of suitability for industrialized production, is a kind of very economic, easy method for preparing p-hydroxybenzylcyanide.
Embodiment
Through embodiment the present invention is made further more detailed description below, but the present invention is not limited to these embodiment.
Embodiment 1
In 100mL single port bottle, add 5 gram (0.033mol) phydroxybenzeneactamides, 0.41 gram (1.65mmol) Dibutyltin oxide, ionic liquid bromination N-picoline 0.10 gram and 50mL exsiccant toluene, this reaction mixture reacts in stirring and refluxing.Reaction adopts the TLC detection reaction to carry out degree, developping agent petrol ether/ethyl acetate (volume ratio 2: 1), the R of p-hydroxybenzylcyanide
fAbout=0.6.Behind reaction 19h, reaction finishes, and filtered while hot is removed Dibutyltin oxide and ionic liquid (can recycling), and the gained toluene solution of filtrating is cooled to the crystallization of pulling an oar about 0 ℃.Suction filtration is also dry, obtains p-hydroxybenzylcyanide 4.10 grams, productive rate 94.2%, gas phase analysis purity 98.7%.
m.p.：69-71℃；
1HNMR(CDCl
3，400M)，TMS)：δ3.63(s，2H)，6.51(s，br，1H)，6.85～6.87(d，2H)，7.15-7.17(d，2H)。
13CNMR(100M，CDCl
3，)δ155.8，129.3，121.3，118.6，116.2，22.8。
Embodiment 2
In 250mL single port bottle, add 10 gram (0.066mol) phydroxybenzeneactamides, 0.82 gram (3.3mmol) Dibutyltin oxide, ionic liquid bromination N-butyl-pyridinium 0.20 gram and 120mL exsiccant toluene, this reaction mixture reacts in stirring and refluxing.Reaction adopts the TLC detection reaction to carry out degree.Behind reaction 19h, reaction finishes, and filtered while hot is removed Dibutyltin oxide and ionic liquid (can recycling), and the gained toluene solution of filtrating is cooled to the crystallization of pulling an oar about 0 ℃.Suction filtration is also dry, obtains p-hydroxybenzylcyanide 8.60 grams, productive rate 97.7%, gas phase analysis purity 98.8%.
Embodiment 3
In 250mL single port bottle, add 10 gram (0.066mol) phydroxybenzeneactamides, 0.82 gram (3.3mmol) Dibutyltin oxide, bromination 1-methyl-3-ethyl imidazol(e) salt 0.20 gram and 120mL exsiccant toluene, this reaction mixture reacts in stirring and refluxing.Reaction adopts the TLC detection reaction to carry out degree.Behind reaction 18h, reaction finishes, and filtered while hot is removed Dibutyltin oxide and ionic liquid (can recycling), and the gained toluene solution of filtrating is cooled to the crystallization of pulling an oar about 0 ℃.Suction filtration is also dry, obtains p-hydroxybenzylcyanide 8.50 grams, productive rate 96.6%, gas phase analysis purity 98.8%.
Embodiment 4
In 250mL single port bottle, add 10 gram (0.066mol) phydroxybenzeneactamides, 1.2 gram (4.82mmol) Dibutyltin oxides, bromination 1-methyl-3-ethyl imidazol(e) salt 0.20 gram and 120mL exsiccant ethylbenzene, this reaction mixture reacts in stirring and refluxing.Reaction adopts the TLC detection reaction to carry out degree.Behind reaction 18h, reaction finishes, and filtered while hot is removed Dibutyltin oxide and ionic liquid (can recycling), and the gained toluene solution of filtrating is cooled to the crystallization of pulling an oar about 0 ℃.Suction filtration is also dry, obtains p-hydroxybenzylcyanide 8.55 grams, productive rate 97.2%, gas phase analysis purity 98.8%.
Embodiment 5
In 250mL single port bottle, add Dibutyltin oxide and the ionic liquid and the 120mL exsiccant toluene of the recovery among 10 gram (0.066mol) phydroxybenzeneactamides, the embodiment 3, this reaction mixture reacts in stirring and refluxing.Reaction adopts the TLC detection reaction to carry out degree.Behind reaction 18h, reaction finishes, and filtered while hot is removed Dibutyltin oxide and ionic liquid (can recycling), and the gained toluene solution of filtrating is cooled to the crystallization of pulling an oar about 0 ℃.Suction filtration is also dry, obtains p-hydroxybenzylcyanide 8.48 grams, productive rate 96.4%, gas phase analysis purity 98.6%.
Embodiment 6
In 250mL single port bottle, add 10 gram (0.066mol) phydroxybenzeneactamides, the Dibutyltin oxide of the recovery among the embodiment 5 and ionic liquid and 120mL exsiccant toluene, this reaction mixture reacts in stirring and refluxing.Reaction adopts the TLC detection reaction to carry out degree.Behind reaction 18h, reaction finishes, and filtered while hot is removed Dibutyltin oxide and ionic liquid (can recycling), and the gained toluene solution of filtrating is cooled to the crystallization of pulling an oar about 0 ℃.Suction filtration is also dry, obtains p-hydroxybenzylcyanide 8.46 grams, productive rate 96.1%, gas phase analysis purity 98.6%.
Claims (10)
1. the preparation method of a p-hydroxybenzylcyanide; This method comprises: be raw material with the phydroxybenzeneactamide; In organic solvent, in the presence of Dibutyltin oxide and ionic liquefaction compound, phydroxybenzeneactamide carries out dehydration reaction; Obtain p-hydroxybenzylcyanide, wherein said organic solvent is selected from toluene, ethylbenzene, isopropyl benzene, n-butyl benzene, benzene, YLENE, oil of mirbane, chlorobenzene and its mixture.
2. the preparation method of p-hydroxybenzylcyanide according to claim 1 is characterized in that, said ionic liquefaction compound is selected among the ionic liquefaction compound that following structural formula representes:
In said structural formula A and B, R
1Be C
1～C
6Alkyl, X is Cl or Br.
3. the preparation method of p-hydroxybenzylcyanide according to claim 2 is characterized in that, in said structural formula A and B, and R
1Be C
1～C
3Alkyl; X is Br.
4. the preparation method of p-hydroxybenzylcyanide according to claim 3 is characterized in that, said ionic liquefaction compound is bromination N-butyl-pyridinium, bromination N-picoline, bromination 1-methyl-3-ethyl imidazol(e) salt or bromination 1-methyl-3-propyl imidazole salt.
5. the preparation method of p-hydroxybenzylcyanide according to claim 1 is characterized in that, said organic solvent is toluene, ethylbenzene or isopropyl benzene.
6. the preparation method of p-hydroxybenzylcyanide according to claim 5 is characterized in that, said organic solvent is a toluene.
7. according to the preparation method of each described p-hydroxybenzylcyanide in the claim 1～6, it is characterized in that in the dehydration reaction of phydroxybenzeneactamide, the mol ratio of Dibutyltin oxide and phydroxybenzeneactamide is 0.01: 1.0～0.15: 1.0; The consumption of said organic solvent is to make that this consumption of organic solvent is 5～50 times of phydroxybenzeneactamide consumption, by weight; The consumption of said ionic liquefaction compound is to make that this ionic liquid compound amount is 0.5～10% of a phydroxybenzeneactamide consumption, by weight.
8. the preparation method of p-hydroxybenzylcyanide according to claim 7 is characterized in that, in the dehydration reaction of phydroxybenzeneactamide, the mol ratio of Dibutyltin oxide and phydroxybenzeneactamide is 0.05: 1.0; The consumption of said organic solvent is to make that this consumption of organic solvent is 30 times of phydroxybenzeneactamide consumption, by weight; The consumption of said ionic liquefaction compound is to make that this ionic liquid compound amount is 2% of a phydroxybenzeneactamide consumption, by weight.
9. according to the preparation method of each described p-hydroxybenzylcyanide in the claim 1～8; It is characterized in that; In the dehydration reaction of phydroxybenzeneactamide, stirring reaction 15～20h under the temperature in the reflux temperature-30 of said organic solvent ℃ to the reflow temperature range of said organic solvent; Adopt TLC detection reaction process, developping agent petrol ether/ethyl acetate 2: 1 by volume, the R of p-hydroxybenzylcyanide
fAbout=0.6; After reaction finished, filtered while hot was removed Dibutyltin oxide and ionic liquefaction compound, and filtrating is carried out crystallisation by cooling, crossed and filtered pure white product p-hydroxybenzylcyanide.
10. the preparation method of p-hydroxybenzylcyanide according to claim 9 is characterized in that, in the dehydration reaction of phydroxybenzeneactamide, and stirring reaction 15～20h under the reflux temperature of organic solvent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201210121266.2A CN102675148B (en) | 2012-04-23 | 2012-04-23 | Preparation method of hydroxybenzyl cyanide |
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| CN201210121266.2A CN102675148B (en) | 2012-04-23 | 2012-04-23 | Preparation method of hydroxybenzyl cyanide |
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| CN102675148B CN102675148B (en) | 2014-02-26 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103387519A (en) * | 2013-07-01 | 2013-11-13 | 安徽省旌德县天益医药化工厂 | Preparation method for 4-hydroxybenzyl cyanide |
| CN103450046A (en) * | 2013-09-11 | 2013-12-18 | 嘉兴学院 | Method for preparing para hydroxybenzene acetonitrile |
| CN104892435A (en) * | 2015-04-07 | 2015-09-09 | 嘉兴学院 | Preparation method of diphenhydramine |
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| US4317781A (en) * | 1980-04-23 | 1982-03-02 | Imperial Chemical Industries Limited | Process for the manufacture of p-hydroxybenzyl cyanide |
| CN101182308A (en) * | 2006-11-13 | 2008-05-21 | 浙江工业大学 | Imidazole chiral ionic liquids containing double function groups as well as preparation method and uses thereof |
| CN102180810A (en) * | 2011-03-10 | 2011-09-14 | 青岛科技大学 | Preparation method of 4-hydroxyphenylacetonitrile |
-
2012
- 2012-04-23 CN CN201210121266.2A patent/CN102675148B/en not_active Expired - Fee Related
Patent Citations (3)
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| US4317781A (en) * | 1980-04-23 | 1982-03-02 | Imperial Chemical Industries Limited | Process for the manufacture of p-hydroxybenzyl cyanide |
| CN101182308A (en) * | 2006-11-13 | 2008-05-21 | 浙江工业大学 | Imidazole chiral ionic liquids containing double function groups as well as preparation method and uses thereof |
| CN102180810A (en) * | 2011-03-10 | 2011-09-14 | 青岛科技大学 | Preparation method of 4-hydroxyphenylacetonitrile |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103387519A (en) * | 2013-07-01 | 2013-11-13 | 安徽省旌德县天益医药化工厂 | Preparation method for 4-hydroxybenzyl cyanide |
| CN103387519B (en) * | 2013-07-01 | 2015-04-01 | 安徽省旌德县天益医药化工厂 | Preparation method for 4-hydroxybenzyl cyanide |
| CN103450046A (en) * | 2013-09-11 | 2013-12-18 | 嘉兴学院 | Method for preparing para hydroxybenzene acetonitrile |
| CN104892435A (en) * | 2015-04-07 | 2015-09-09 | 嘉兴学院 | Preparation method of diphenhydramine |
| CN104892435B (en) * | 2015-04-07 | 2016-08-24 | 嘉兴学院 | The preparation method of diphenhydramine |
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