CN103450046A - Method for preparing para hydroxybenzene acetonitrile - Google Patents
Method for preparing para hydroxybenzene acetonitrile Download PDFInfo
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- CN103450046A CN103450046A CN2013104134439A CN201310413443A CN103450046A CN 103450046 A CN103450046 A CN 103450046A CN 2013104134439 A CN2013104134439 A CN 2013104134439A CN 201310413443 A CN201310413443 A CN 201310413443A CN 103450046 A CN103450046 A CN 103450046A
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- hydroxyphenylethanol
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- hypochlorite
- hydroxybenzylcyanide
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- WEROLFNOZCOTQT-UHFFFAOYSA-N Cc1ccc(C[Zn])cc1 Chemical compound Cc1ccc(C[Zn])cc1 WEROLFNOZCOTQT-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention belongs to the field of organic chemical synthesis, and relates to a method for preparing para hydroxybenzene acetonitrile. The method comprises the following step: carrying out oxidation, ammoniation and reoxidation reactions on para hydroxybenzene ethanol in the presence of ammonia water and hypochlorite by taking the para hydroxybenzene ethanol as a raw material and water as a reaction medium to obtain the para hydroxybenzene acetonitrile. The process route for oxidation, ammoniation and reoxidation on the para hydroxybenzene ethanol by taking the lower-price (relative to para hydroxybenzene acetamide) para hydroxybenzene ethanol as the raw material has the characteristics of mildness in reaction condition and high yield; meanwhile, the production cost of the para hydroxybenzene acetonitrile is greatly reduced; the technical route has the characteristics of short route, easiness and convenience for operation, mildness in reaction condition and easiness for industrialized production and is a very economic, simple and convenient method for preparing the para hydroxybenzene acetonitrile.
Description
Technical field
The invention belongs to the organic chemical synthesis field, more specifically, relate to a kind of method for preparing 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 large, has good market outlook.
The synthetic route of the p-hydroxybenzylcyanide of having reported at present is less, mainly adopts following four synthetic routes to synthesize:
(1) take benzyl cyanide as raw material synthetic: this technique be take benzyl cyanide as raw material, be total to four-step reaction through nitrated, reduction, diazotization and hydrolysis and prepare p-hydroxybenzylcyanide (" synthesizing of Actarit ", " 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, 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), use hypertoxic sodium cyanide or potassium cyanide reagent in this technique, 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 to prepare p-hydroxybenzylcyanide for dewatering agent dewaters.Can produce a large amount of hydrogen chloride emissions in this technique, 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 the standby p-hydroxybenzylcyanide of thionyl chloride Dehydration, 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.
(4) Chinese patent application CN102675148A be also take phydroxybenzeneactamide as raw material synthetic: this technique be 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.This technique has the reaction conditions gentleness, pollution-free, catalyst recirculation is used and the high characteristics of productive rate, but the price of phydroxybenzeneactamide raw material is relatively high at present, thereby causes the price of product p-hydroxybenzylcyanide also to keep higher level.
Summary of the invention
In view of this, the object of the present invention is to provide and a kind ofly take p-hydroxyphenylethanol and prepare the method for p-hydroxybenzylcyanide as raw material, p-hydroxyphenylethanol is easy to get, inexpensive, and this preparation technology is easy, reaction conditions is gentle, cost is low, the product yield is high.
According to the present invention, the invention provides a kind of method for preparing p-hydroxybenzylcyanide, the method comprises: take p-hydroxyphenylethanol as raw material, take water as reaction medium, under ammoniacal liquor and hypochlorite existence, p-hydroxyphenylethanol carries out oxidation, ammonification and reoxidizes reaction, obtains p-hydroxybenzylcyanide.
Below, specifically describe preparation method of the present invention.
In preparation method provided by the invention, described hypochlorite is clorox, potassium hypochlorite, Losantin or magnesium hypochlorite, and most preferably is clorox.
In oxidation, the ammonification of p-hydroxyphenylethanol and reoxidizing reaction, the mol ratio of ammonia and p-hydroxyphenylethanol is 1.0:1.0～8.0:1.0, is preferably 2.0:1.0～4.0:1.0, most preferably is 3.0:1.0; The mol ratio of hypochlorite and p-hydroxyphenylethanol is 2.0:1.0～6.0:1.0, is preferably 2.0:1.0～4.0:1.0, most preferably is 3.0:1.0.
Described ammoniacal liquor preferably adopts the ammoniacal liquor of 10wt%～35wt% concentration, preferably adopts the ammoniacal liquor of 28wt%; Described hypochlorite adopts the aqueous hypochlorite solution of 1wt%～30wt% concentration, preferably adopts the aqueous hypochlorite solution of 6.5wt%, and adds reaction solution in the mode dripped.
In oxidation, the ammonification of p-hydroxyphenylethanol and reoxidizing reaction, at the temperature refluxed at room temperature to reaction solution, and preferred stirring reaction 5～24h at the temperature of 40 ℃～60 ℃, the temperature height can cause the volatilization loss of ammoniacal liquor; 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, reaction mixture is cooled to 0 ℃ of left and right and carries out crystallization, filter to obtain pure white product p-hydroxybenzylcyanide.
Take water as reaction medium, and under ammoniacal liquor and hypochlorite existence, p-hydroxyphenylethanol carries out oxidation, ammonification and reoxidizes reaction, this reaction formula following (hypochlorous sodium is example):
Reaction process is as follows: at first p-hydroxyphenylethanol is become para hydroxybenzene acetaldehyde by hypochlorite oxidation, and then para hydroxybenzene acetaldehyde and ammonia react generate imines, and last imines is become p-hydroxybenzylcyanide by hypochlorite oxidation again.
In sum, the present invention has following advantage:
It is raw material that the p-hydroxyphenylethanol of price comparison cheap (phydroxybenzeneactamide relatively) is take in the present invention, take water as reaction medium, under ammoniacal liquor and hypochlorite existence, p-hydroxyphenylethanol is through oxidation, ammonification and reoxidize and prepare p-hydroxybenzylcyanide, there are reaction conditions gentleness, characteristics that productive rate is high, also greatly reduce the production cost of p-hydroxybenzylcyanide simultaneously.
Therefore, the preparation method of p-hydroxybenzylcyanide of the present invention, this technological line has the advantages that route is short, easy and simple to handle, reaction conditions is gentle and be easy to suitability for industrialized production, is a kind of very economical, easy method for 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
Add 4.56 grams (0.033mol) p-hydroxyphenylethanol in 100mL there-necked flask (being equipped with thermometer, magnetic agitation, reflux condensing tube and constant pressure funnel), ammoniacal liquor (28wt%) 8.8mL(0.132mol), this reaction mixture is heated to 50 ℃, p-hydroxyphenylethanol is dissolved, then, slowly drip the aqueous sodium hypochlorite solution 36.3mL(0.073mol of 6.5wt%), control temperature of reaction at 50 ℃.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
fapproximately=0.6.After reaction 20h, react complete, reaction solution is cooled to 0 ℃ of left and right crystallization.Suction filtration is also dry, obtains p-hydroxybenzylcyanide 4.13 grams, productive rate 95.0%, gas chromatographic analysis purity 98.8%.
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
Add 9.12 grams (0.066mol) p-hydroxyphenylethanol, ammoniacal liquor (28wt%) 17.6mL(0.264mol in 250mL there-necked flask (being equipped with thermometer, magnetic agitation, reflux condensing tube and constant pressure funnel)), this reaction mixture is heated to 60 ℃, p-hydroxyphenylethanol is dissolved.Then, slowly drip the aqueous sodium hypochlorite solution 99.0mL(0.198mol of 6.5wt%), control temperature of reaction at 60 ℃.Reaction adopts the TLC detection reaction to carry out degree.After reaction 10h, react complete, reaction solution is cooled to 0 ℃ of left and right crystallization.Suction filtration is also dry, obtains p-hydroxybenzylcyanide 8.63 grams, productive rate 98.2%, gas chromatographic analysis purity 99.0%.
Embodiment 3
Add 9.12 grams (0.066mol) p-hydroxyphenylethanol, ammoniacal liquor (35wt%) 16.0mL(0.30mol in 250mL there-necked flask (being equipped with thermometer, magnetic agitation, reflux condensing tube and constant pressure funnel)), this reaction mixture is heated to 60 ℃, p-hydroxyphenylethanol is dissolved.Then, slowly drip the aqueous sodium hypochlorite solution 99.0mL(0.198mol of 6.5wt%), control temperature of reaction at 60 ℃.Reaction adopts the TLC detection reaction to carry out degree.After reaction 9h, react complete, reaction solution is cooled to 0 ℃ of left and right crystallization.Suction filtration is also dry, obtains p-hydroxybenzylcyanide 8.65 grams, productive rate 98.4%, gas chromatographic analysis purity 99.2%.
Embodiment 4
Add 9.12 grams (0.066mol) p-hydroxyphenylethanol, ammoniacal liquor (28wt%) 20.0mL(0.30mol in 250mL there-necked flask (being equipped with thermometer, magnetic agitation, reflux condensing tube and constant pressure funnel)), this reaction mixture is heated to 60 ℃, p-hydroxyphenylethanol is dissolved.Then, slowly drip the aqueous sodium hypochlorite solution 43.0mL(0.198mol of 15.0wt%), control temperature of reaction at 60 ℃.Reaction adopts the TLC detection reaction to carry out degree.After reaction 9h, react complete, reaction solution is cooled to 0 ℃ of left and right crystallization.Suction filtration is also dry, obtains p-hydroxybenzylcyanide 8.65 grams, productive rate 98.4%, gas chromatographic analysis purity 99.2%.
Embodiment 5
Add 30 grams (0.217mol) p-hydroxyphenylethanol, ammoniacal liquor (15wt%) 162.0mL(1.3mol in 500mL there-necked flask (being equipped with thermometer, magnetic agitation, reflux condensing tube and constant pressure funnel)), this reaction mixture is heated to 60 ℃, and p-hydroxyphenylethanol is dissolved.Then, slowly drip the aqueous sodium hypochlorite solution 325.0mL(0.651mol of 6.5wt%), control temperature of reaction at 60 ℃.Reaction adopts the TLC detection reaction to carry out degree.After reaction 7h, react complete, reaction solution is cooled to 0 ℃ of left and right crystallization.Suction filtration is also dry, obtains p-hydroxybenzylcyanide 28.7 grams, productive rate 99.3%, gas chromatographic analysis purity 99.5%.
Embodiment 6
Add 30 grams (0.217mol) p-hydroxyphenylethanol, ammoniacal liquor (28wt%) 73.4mL(1.1mol in 500mL there-necked flask (being equipped with thermometer, magnetic agitation, reflux condensing tube and constant pressure funnel)), this reaction mixture is heated to 55 ℃, and p-hydroxyphenylethanol is dissolved.Then, slowly drip the aqueous sodium hypochlorite solution 325.0mL(0.651mol of 6.5wt%), control temperature of reaction at 55 ℃.Reaction adopts the TLC detection reaction to carry out degree.After reaction 9h, react complete, reaction solution is cooled to 0 ℃ of left and right crystallization.Suction filtration is also dry, obtains p-hydroxybenzylcyanide 28.5 grams, productive rate 98.6%, gas chromatographic analysis purity 99.1%.
Claims (10)
1. a method for preparing p-hydroxybenzylcyanide, the method comprises: take p-hydroxyphenylethanol as raw material, take water as reaction medium, under ammoniacal liquor and hypochlorite exist, p-hydroxyphenylethanol carries out oxidation, ammonification and reoxidizes reaction, obtains p-hydroxybenzylcyanide.
2. the method for preparing p-hydroxybenzylcyanide according to claim 1, is characterized in that, described hypochlorite is clorox, potassium hypochlorite, Losantin or magnesium hypochlorite.
3. the method for preparing p-hydroxybenzylcyanide according to claim 2, is characterized in that, described hypochlorite is clorox.
4. according to the described method for preparing p-hydroxybenzylcyanide of any one in claims 1 to 3, it is characterized in that, in oxidation, the ammonification of p-hydroxyphenylethanol and reoxidizing reaction, the mol ratio of ammonia and p-hydroxyphenylethanol is 1.0:1.0～8.0:1.0, and the mol ratio of hypochlorite and p-hydroxyphenylethanol is 2.0:1.0～6.0:1.0.
5. the method for preparing p-hydroxybenzylcyanide according to claim 4, it is characterized in that, in oxidation, the ammonification of p-hydroxyphenylethanol and reoxidizing reaction, the mol ratio 2.0:1.0 of ammonia and p-hydroxyphenylethanol～4.0:1.0, the mol ratio of hypochlorite and p-hydroxyphenylethanol is 2.0:1.0～4.0:1.0.
6. the method for preparing p-hydroxybenzylcyanide according to claim 5, it is characterized in that, in oxidation, the ammonification of p-hydroxyphenylethanol and reoxidizing reaction, the mol ratio 3.0:1.0 of ammonia and p-hydroxyphenylethanol, the mol ratio of hypochlorite and p-hydroxyphenylethanol is 3.0:1.0.
7. according to the described method for preparing p-hydroxybenzylcyanide of any one in claims 1 to 3, it is characterized in that, described ammoniacal liquor adopts the ammoniacal liquor of 10wt%～35wt% concentration, and described hypochlorite adopts the aqueous hypochlorite solution of 1wt%～30wt% concentration, and adds reaction solution in the mode dripped.
8. the method for preparing p-hydroxybenzylcyanide according to claim 7, is characterized in that, described ammoniacal liquor adopts the ammoniacal liquor of 28wt% concentration, and described hypochlorite adopts the aqueous hypochlorite solution of 6.5wt%.
9. according to the described method for preparing p-hydroxybenzylcyanide of any one in claims 1 to 3, it is characterized in that, in oxidation, the ammonification of p-hydroxyphenylethanol and reoxidizing reaction, reaction is stirred and is carried out 5～24h at the temperature of 40 ℃～60 ℃.
10. the method for preparing p-hydroxybenzylcyanide according to claim 1, is characterized in that, described hypochlorite is clorox; In oxidation, the ammonification of p-hydroxyphenylethanol and reoxidizing reaction, the mol ratio 3.0:1.0 of ammonia and p-hydroxyphenylethanol, the mol ratio of hypochlorite and p-hydroxyphenylethanol is 3.0:1.0; Described ammoniacal liquor adopts the ammoniacal liquor of 28wt% concentration, and described hypochlorite adopts the aqueous hypochlorite solution of 6.5wt%; Reaction is stirred and is carried out 5～24h at the temperature of 40 ℃～60 ℃.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111804285A (en) * | 2020-07-15 | 2020-10-23 | 哈尔滨工程大学 | Amino-amidoxime group bifunctional hypercrosslinked microporous uranium adsorbent and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102180810A (en) * | 2011-03-10 | 2011-09-14 | 青岛科技大学 | Preparation method of 4-hydroxyphenylacetonitrile |
| CN102675148A (en) * | 2012-04-23 | 2012-09-19 | 嘉兴学院 | Preparation method of hydroxybenzyl cyanide |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102180810A (en) * | 2011-03-10 | 2011-09-14 | 青岛科技大学 | Preparation method of 4-hydroxyphenylacetonitrile |
| CN102675148A (en) * | 2012-04-23 | 2012-09-19 | 嘉兴学院 | Preparation method of hydroxybenzyl cyanide |
Non-Patent Citations (1)
| Title |
|---|
| 顾龙勤等: "甲苯氨氧化制苯甲腈研究", 《工业催化》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111804285A (en) * | 2020-07-15 | 2020-10-23 | 哈尔滨工程大学 | Amino-amidoxime group bifunctional hypercrosslinked microporous uranium adsorbent and preparation method thereof |
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