CN102675148B - Preparation method of hydroxybenzyl cyanide - Google Patents
Preparation method of hydroxybenzyl cyanide Download PDFInfo
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- CN102675148B CN102675148B CN201210121266.2A CN201210121266A CN102675148B CN 102675148 B CN102675148 B CN 102675148B CN 201210121266 A CN201210121266 A CN 201210121266A CN 102675148 B CN102675148 B CN 102675148B
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- hydroxybenzylcyanide
- organic solvent
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- phydroxybenzeneactamide
- reaction
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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 organic chemical synthesis field, 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 domestic and international market demand is large, has good market outlook.
The synthetic route of the p-hydroxybenzylcyanide of having reported is at present less, and below main employing, three synthetic routes are synthesized:
(1) take benzyl cyanide as raw material synthetic: this technique be take benzyl cyanide as raw material, through nitrated, reduction, diazotization and hydrolysis, be total to four-step reaction and prepare p-hydroxybenzylcyanide (" synthesizing of Actarit ", < < University Of Hebei journal: the 2nd phase of natural science edition > >, 2008,178～200.), four-step reaction total recovery is less than 30%.This reaction process step is many, processes complexity, uses two kinds of strong acid of a large amount of vitriol oils and concentrated nitric acid in reaction process, not only serious to equipment corrosion, produces a large amount of three wastes processing costs high simultaneously.Along with the innovation of technology, this technique will be eliminated.
(2) take to hydroxyl benzyl chlorine as raw material synthetic: this technique is with to hydroxyl benzyl chlorine and sodium cyanide or potassium cyanide reaction preparation (Czech Rep., P2009301063), in this technique, use hypertoxic sodium cyanide or potassium cyanide reagent, environmental pollution is serious, will be replaced gradually.
(3) Chinese patent application CN102180810A take phydroxybenzeneactamide as raw material synthetic: this technique be take phydroxybenzeneactamide as raw material, utilizes thionyl chloride for dewatering agent dewaters, to prepare p-hydroxybenzylcyanide.In this technique, can produce a large amount of hydrogen chloride emissions, complex disposal process need activated carbon decolorizing and repeatedly recrystallization obtain product, purity can reach 95% left and right.In addition, the inventor be take phydroxybenzeneactamide as starting raw material, adopts aforesaid method to utilize thionyl chloride Dehydration for p-hydroxybenzylcyanide, in reaction, by product is more, the product colour of preparation is more yellow, and productive rate is only in 45% left and right, and the height of the productive rate 95.5% that this patent application is not reported.
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, product yield is high, to overcome the above-mentioned defect existing in prior art.
According to the present invention, the invention provides a kind of preparation method of p-hydroxybenzylcyanide, the method comprises: take phydroxybenzeneactamide as raw material, in organic solvent, under Dibutyltin oxide and the existence of 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, dimethylbenzene, oil of mirbane, chlorobenzene and its mixture.
Below, specifically describe preparation method of the present invention.
In the present invention, described organic solvent is selected from toluene, ethylbenzene, isopropyl benzene, n-butyl benzene, benzene, dimethylbenzene, oil of mirbane, chlorobenzene and its mixture, is preferably toluene, ethylbenzene or isopropyl benzene, and most preferably is toluene.
Described ionic liquefaction compound (hereinafter referred ILs) is for being selected among the ionic liquefaction compound that following structural formula represents:
In described structural formula A and B, R
1for C
1～C
6alkyl, X is Cl or Br.In the present invention, described 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 example of this ionic liquefaction compound can be bromination N-butyl-pyridinium, bromination N-picoline, 1-ethyl-3-methyl-imidazolium bromine 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 described organic solvent is that to make this consumption of organic solvent be 5～50 times of phydroxybenzeneactamide consumption, most preferably is 30 times, by weight; The consumption of described ionic liquefaction compound is that to make this ionic liquid compound amount be 0.5～10% of phydroxybenzeneactamide consumption, most preferably is 2%, by weight.
In the dehydration reaction of phydroxybenzeneactamide, in reflux temperature-30 of described organic solvent ℃ to the temperature in the reflow temperature range of described organic solvent, and preferred stirring reaction 15～20h under the reflux temperature of organic solvent; Adopt TLC detection reaction process (developping agent petrol ether/ethyl acetate (volume ratio 2: 1), the R of p-hydroxybenzylcyanide
fapproximately=0.6); After completion of the reaction, filtered while hot is removed Dibutyltin oxide and ionic liquefaction compound, and filtrate is carried out crystallisation by cooling, filters to obtain pure white product p-hydroxybenzylcyanide.
When take toluene as solvent, under Dibutyltin oxide and the existence of ionic liquefaction compound, phydroxybenzeneactamide carries out dehydration reaction, and this reaction formula is as follows:
In sum, tool of the present invention has the following advantages:
In the present invention, take phydroxybenzeneactamide as raw material, Dibutyltin oxide is dewatering agent, and ionic liquefaction compound is catalyzer, and toluene etc. are prepared p-hydroxybenzylcyanide for solvent and band aqua, have reaction conditions gentleness, the feature that pollution-free and productive rate is high; Dibutyltin oxide and ionic liquid can recycle more than 10 times, and yield remains unchanged substantially.
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 feature of suitability for industrialized production, is a kind of very economical, easy method of preparing p-hydroxybenzylcyanide.
Embodiment
Below by embodiment, the present invention is made to further more detailed description, but the present invention is not limited to these embodiment.
Embodiment 1
In 100mL single port bottle, add 5 grams of (0.033mol) phydroxybenzeneactamides, 0.41 gram of (1.65mmol) Dibutyltin oxide, 0.10 gram of ionic liquid bromination N-picoline and the dry toluene of 50mL, this reaction mixture reacts in stirring and refluxing.Reaction adopts TLC detection reaction to carry out degree, developping agent petrol ether/ethyl acetate (volume ratio 2: 1), the R of p-hydroxybenzylcyanide
fapproximately=0.6.After reaction 19h, react complete, filtered while hot is removed Dibutyltin oxide and ionic liquid (can recycling), and gained filtrate toluene solution is cooled to the about 0 ℃ crystallization of pulling an oar.Suction filtration is also dry, obtains 4.10 grams of p-hydroxybenzylcyanides, 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 grams of (0.066mol) phydroxybenzeneactamides, 0.82 gram of (3.3mmol) Dibutyltin oxide, 0.20 gram of ionic liquid bromination N-butyl-pyridinium and the dry toluene of 120mL, this reaction mixture reacts in stirring and refluxing.Reaction adopts TLC detection reaction to carry out degree.After reaction 19h, react complete, filtered while hot is removed Dibutyltin oxide and ionic liquid (can recycling), and gained filtrate toluene solution is cooled to the about 0 ℃ crystallization of pulling an oar.Suction filtration is also dry, obtains 8.60 grams of p-hydroxybenzylcyanides, productive rate 97.7%, gas phase analysis purity 98.8%.
Embodiment 3
In 250mL single port bottle, add 10 grams of (0.066mol) phydroxybenzeneactamides, 0.82 gram of (3.3mmol) Dibutyltin oxide, 0.20 gram of 1-ethyl-3-methyl-imidazolium bromine salt and the dry toluene of 120mL, this reaction mixture reacts in stirring and refluxing.Reaction adopts TLC detection reaction to carry out degree.After reaction 18h, react complete, filtered while hot is removed Dibutyltin oxide and ionic liquid (can recycling), and gained filtrate toluene solution is cooled to the about 0 ℃ crystallization of pulling an oar.Suction filtration is also dry, obtains 8.50 grams of p-hydroxybenzylcyanides, productive rate 96.6%, gas phase analysis purity 98.8%.
Embodiment 4
In 250mL single port bottle, add 10 grams of (0.066mol) phydroxybenzeneactamides, 1.2 grams of (4.82mmol) Dibutyltin oxides, 0.20 gram of 1-ethyl-3-methyl-imidazolium bromine salt and the dry ethylbenzene of 120mL, this reaction mixture reacts in stirring and refluxing.Reaction adopts TLC detection reaction to carry out degree.After reaction 18h, react complete, filtered while hot is removed Dibutyltin oxide and ionic liquid (can recycling), and gained filtrate toluene solution is cooled to the about 0 ℃ crystallization of pulling an oar.Suction filtration is also dry, obtains 8.55 grams of p-hydroxybenzylcyanides, productive rate 97.2%, gas phase analysis purity 98.8%.
Embodiment 5
The Dibutyltin oxide and ionic liquid and the dry toluene of 120mL that in 250mL single port bottle, add the recovery in 10 grams of (0.066mol) phydroxybenzeneactamides, embodiment 3, this reaction mixture reacts in stirring and refluxing.Reaction adopts TLC detection reaction to carry out degree.After reaction 18h, react complete, filtered while hot is removed Dibutyltin oxide and ionic liquid (can recycling), and gained filtrate toluene solution is cooled to the about 0 ℃ crystallization of pulling an oar.Suction filtration is also dry, obtains 8.48 grams of p-hydroxybenzylcyanides, productive rate 96.4%, gas phase analysis purity 98.6%.
Embodiment 6
In 250mL single port bottle, add 10 grams of (0.066mol) phydroxybenzeneactamides, the toluene that the Dibutyltin oxide of the recovery in embodiment 5 and ionic liquid and 120mL are dry, this reaction mixture reacts in stirring and refluxing.Reaction adopts TLC detection reaction to carry out degree.After reaction 18h, react complete, filtered while hot is removed Dibutyltin oxide and ionic liquid (can recycling), and gained filtrate toluene solution is cooled to the about 0 ℃ crystallization of pulling an oar.Suction filtration is also dry, obtains 8.46 grams of p-hydroxybenzylcyanides, productive rate 96.1%, gas phase analysis purity 98.6%.
Claims (10)
1. the preparation method of a p-hydroxybenzylcyanide, the method comprises: take phydroxybenzeneactamide as raw material, in organic solvent, under Dibutyltin oxide and the existence of 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, dimethylbenzene, oil of mirbane, chlorobenzene and its mixture
Described ionic liquefaction compound is selected among the ionic liquefaction compound that following structural formula represents:
In described structural formula A and B, R
1for C
1～C
6alkyl, X is Cl or Br.
2. the preparation method of p-hydroxybenzylcyanide according to claim 1, is characterized in that, in described structural formula A and B, and R
1for C
1～C
3alkyl; X is Br.
3. the preparation method of p-hydroxybenzylcyanide according to claim 1, is characterized in that, described ionic liquefaction compound is bromination N-butyl-pyridinium, bromination N-picoline, 1-ethyl-3-methyl-imidazolium bromine salt or bromination 1-methyl-3-propyl imidazole salt.
4. the preparation method of p-hydroxybenzylcyanide according to claim 1, is characterized in that, described organic solvent is toluene, ethylbenzene or isopropyl benzene.
5. the preparation method of p-hydroxybenzylcyanide according to claim 4, is characterized in that, described organic solvent is toluene.
6. according to the preparation method of the p-hydroxybenzylcyanide described in any one in claim 1～5, 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 described organic solvent is that to make this consumption of organic solvent be 5～50 times of phydroxybenzeneactamide consumption, by weight; The consumption of described ionic liquefaction compound is that to make this ionic liquid compound amount be 0.5～10% of phydroxybenzeneactamide consumption, by weight.
7. the preparation method of p-hydroxybenzylcyanide according to claim 6, 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 described organic solvent is that to make this consumption of organic solvent be 30 times of phydroxybenzeneactamide consumption, by weight; The consumption of described ionic liquefaction compound is that to make this ionic liquid compound amount be 2% of phydroxybenzeneactamide consumption, by weight.
8. according to the preparation method of the p-hydroxybenzylcyanide described in any one in claim 1～5, it is characterized in that, in the dehydration reaction of phydroxybenzeneactamide, in reflux temperature-30 of described organic solvent ℃ to stirring reaction 15～20h at the temperature in the reflow temperature range of described organic solvent; Adopt TLC detection reaction process, developping agent petrol ether/ethyl acetate is 2:1 by volume, the R of p-hydroxybenzylcyanide
f=0.6; After completion of the reaction, filtered while hot is removed Dibutyltin oxide and ionic liquefaction compound, and filtrate is carried out crystallisation by cooling, filters to obtain pure white product p-hydroxybenzylcyanide.
9. the preparation method of p-hydroxybenzylcyanide according to claim 8, is characterized in that, in the dehydration reaction of phydroxybenzeneactamide, and stirring reaction 15～20h under the reflux temperature of organic solvent.
10. the preparation method of p-hydroxybenzylcyanide according to claim 6, it is characterized in that, in the dehydration reaction of phydroxybenzeneactamide, in reflux temperature-30 of described organic solvent ℃ to stirring reaction 15～20h at the temperature in the reflow temperature range of described organic solvent; Adopt TLC detection reaction process, developping agent petrol ether/ethyl acetate is 2:1 by volume, the R of p-hydroxybenzylcyanide
f=0.6; After completion of the reaction, filtered while hot is removed Dibutyltin oxide and ionic liquefaction compound, and filtrate is carried out crystallisation by cooling, filters to obtain pure white product p-hydroxybenzylcyanide.
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| 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 |
| CN103450046B (en) * | 2013-09-11 | 2014-10-15 | 嘉兴学院 | Method for preparing para hydroxybenzene acetonitrile |
| CN104892435B (en) * | 2015-04-07 | 2016-08-24 | 嘉兴学院 | The preparation method of diphenhydramine |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4317781A (en) * | 1980-04-23 | 1982-03-02 | Imperial Chemical Industries Limited | Process for the manufacture of p-hydroxybenzyl cyanide |
| CN102180810A (en) * | 2011-03-10 | 2011-09-14 | 青岛科技大学 | Preparation method of 4-hydroxyphenylacetonitrile |
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| CN101182308B (en) * | 2006-11-13 | 2010-06-09 | 浙江工业大学 | Imidazole chiral ionic liquids containing double function groups as well as preparation method and uses thereof |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4317781A (en) * | 1980-04-23 | 1982-03-02 | Imperial Chemical Industries Limited | Process for the manufacture of p-hydroxybenzyl cyanide |
| CN102180810A (en) * | 2011-03-10 | 2011-09-14 | 青岛科技大学 | Preparation method of 4-hydroxyphenylacetonitrile |
Non-Patent Citations (5)
| Title |
|---|
| Development》.1998,第2卷(第4期), * |
| Joseph Akisanya et al..A Synthesis of Atenolol Using a Nitrile Hydration Catalyst.《Organic Process Research & Development》.1998,第2卷(第4期), |
| Joseph Akisanya et al..A Synthesis of Atenolol Using a Nitrile Hydration Catalyst.《Organic Process Research & * |
| 氨酰心安的合成;王子俊;《浙江化工》;19941231;第25卷(第3期);第28-29页 * |
| 王子俊.氨酰心安的合成.《浙江化工》.1994,第25卷(第3期), |
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