CN1740146A - Prepn process of 2-fluoro-5-trifluoromethyl benzyl cyanide - Google Patents
Prepn process of 2-fluoro-5-trifluoromethyl benzyl cyanide Download PDFInfo
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- CN1740146A CN1740146A CN 200410057246 CN200410057246A CN1740146A CN 1740146 A CN1740146 A CN 1740146A CN 200410057246 CN200410057246 CN 200410057246 CN 200410057246 A CN200410057246 A CN 200410057246A CN 1740146 A CN1740146 A CN 1740146A
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- fluoro
- trifluoromethyl benzyl
- benzyl cyanide
- nitrilation
- reaction
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Abstract
The present invention discloses the preparation process of 2-fluoro-5-trifluoromethyl benzyl cyanide. The preparation process includes the halogenomethylation of p-fluoro trifluoro toluene to produce 2-fluoro-5-trifluoromethyl benzyl halide, and the nitrilation of 2-fluoro-5-trifluoromethyl benzyl halide to produce 2-fluoro-5-trifluoromethyl benzyl cyanide. The present invention has high yield, low cost and high product purity.
Description
Technical field
The present invention relates to the preparation method of 2-fluoro-5-trifluoromethyl benzyl cyanide, particularly by will prepare the method for 2-fluoro-5-trifluoromethyl benzyl cyanide through halomethylation, nitrilation to fluoride trifluoro toluene.
Background technology
2-fluoro-5-trifluoromethyl benzyl cyanide is a kind of new treatment medicine for gynecopathy and the intermediate of oral contraceptive, and present disclosed preparation method is more loaded down with trivial details, and cost is higher.Therefore, research and develop a kind of high yield, to prepare the method for 2-fluoro-5-trifluoromethyl benzyl cyanide cheaply real in necessary.
Summary of the invention
The objective of the invention is provides a kind of high yield, prepares the method for 2-fluoro-5-trifluoromethyl benzyl cyanide cheaply at the deficiencies in the prior art.
For achieving the above object, method of the present invention may further comprise the steps: will be as shown in the formula fluoride trifluoro toluene is generated as shown in the formula the 2-fluoro-5-trifluoromethyl benzyl halogen shown in (II) through halomethylation shown in (I); And will generate as shown in the formula the 2-fluoro-5-trifluoromethyl benzyl cyanide shown in (III) through nitrilation suc as formula the 2-fluoro-5-trifluoromethyl benzyl halogen shown in (II),
Wherein X is Br or Cl.
Halomethylation of the present invention reaction is to make trioxymethylene and halogenating agent and fluoride trifluoro toluene is reacted, and wherein halogenating agent is selected from SOX
2Or HX, X is selected from Br or Cl, is preferably SOCl
2Or HCl.
The temperature of halomethylation reaction of the present invention is preferably 20 ℃-30 ℃.
The used nitrilation agent of cyanation of the present invention is MCN, and wherein M is a metal ion, is preferably K, Na.
Cyanation of the present invention carries out in the presence of alkali, and used alkali is selected from pyridine, N-picoline, N-Methyl pyrrolidone, triethylamine, dimethylamine, K
2CO
3, Na
2CO
3Or its combination, be preferably dimethylamine.
Also comprise the step that each step reaction product is carried out separation and purification in the inventive method.
Compared with prior art, the present invention is by fluoride trifluoro toluene is generated intermediate 2-fluoro-5-trifluoromethyl benzyl halogen through halomethylation, generate 2-fluoro-5-trifluoromethyl benzyl cyanide through nitrilation again, thereby a kind of high yield, preparation method are cheaply provided, and products therefrom purity height, and can be used as the intermediate that medicine for gynecopathy and oral contraceptive are treated by a new generation.
Embodiment
The present invention will be described in more detail below in conjunction with embodiment.
Embodiment
(1) preparation of 2-fluoro-5-trifluoromethyl benzyl chlorine
Drop into the 229g vitriol oil in the 250ml four-hole boiling flask, the frozen water cooling adds trioxymethylene 24.2g down in batches, and control reaction temperature is no more than 30 ℃, finishes and continues stirring reaction 0.5h.Under 20-25 ℃, in 4h, drip thionyl chloride 43.5g, dropwise the back and continue to stir 1h.Under 25-30 ℃, in 2h, in reaction flask, drip, finish under uniform temp and react 4h fluoride trifluoro toluene 20.1g.After reaction finished, standing demix was told upper organic phase 23.8g.
Above-mentioned reacted vitriol oil Recycling Mother Solution is used, added trioxymethylene 4.8g, add thionyl chloride 9.7g, add phenylfluoroform 20.1g, other reaction conditions is the same, obtains organic phase 23.8g.
With the organic layer 47.6g underpressure distillation of two secondary response gained, reclaim unreacted to behind the fluoride trifluoro toluene 16.2g, intercepting 78-81 ℃/30mmHg cut, 2-fluoro-5-trifluoromethyl benzyl chlorine 24.5g, purity is 95.4%, overall yield of reaction is 76%.
Can be with the SOCl that uses in the above-mentioned reaction of HCl gas instead
2HCl is fed in the reaction solution to saturated, and the remaining reaction condition is identical with above-mentioned steps, must organic phase crude product 23.8g.
(2) preparation of 2-fluoro-5-trifluoromethyl benzyl cyanide
The 2-fluoro-5-trifluoromethyl benzyl chlorine 75.1g that adds NaCN 18.7g, dehydrated alcohol 17.7g, 40% dimethylamine 0.45g and make by (1) in the 200ml four-hole boiling flask, reactant stir reflux 12h down.Change reflux into water distilling apparatus after reaction finishes, reclaim ethanol 16.0g.Be cooled to 25 ℃, add 100ml water in reaction flask, stir 0.5h, standing demix gets organic layer 67.4g, with 20ml 5% Na
2CO
3Solution washing organic layer twice, with the 20ml washing once.The underpressure distillation organic layer intercepts 75 ℃ of-78 ℃/3mmHg cuts, gets target product 50.2g, colourless transparent liquid, and purity is 99%, yield 70%.
MS(m/z，M
+)：203；
IR(KBr，cm
-1)：3086，2256，1911，1786，1606，1512，1435，1336，1252，1168，1126，1072，885，831，584。
It should be understood by those skilled in the art that the halogenating agent in the inventive method can be SOX
2, HX, be preferably SOCl
2Or HCl; Nitrilation agent in the inventive method can be MCN, and wherein M is a metal ion, is preferably K, Na.
Should be appreciated that embodiments of the invention only are the non-limitative illustration of the present invention being made in order to understand the present invention better.Those skilled in the art is not departing from the spirit and scope of the present invention and can make various modifications, replacement and change to the present invention, and these modifications, replacement and change still belong to protection scope of the present invention.
Claims (10)
1. method for preparing 2-fluoro-5-trifluoromethyl benzyl cyanide, described method comprises the steps:
To generate 2-fluoro-5-trifluoromethyl benzyl halogen through halomethylation to fluoride trifluoro toluene; And
2-fluoro-5-trifluoromethyl benzyl halogen is generated 2-fluoro-5-trifluoromethyl benzyl cyanide through nitrilation.
2. the method for claim 1, wherein the halomethylation reaction is to make trioxymethylene and halogenating agent and fluoride trifluoro toluene is reacted.
3. method as claimed in claim 2, wherein said halogenating agent is selected from SOX
2Or HX, wherein X is selected from Br or Cl.
4. method as claimed in claim 3, wherein said halogenating agent is selected from SOCl
2Or HCl.
5. the method for claim 1, wherein the temperature of halomethylation reaction is 20 ℃-30 ℃.
6. the method for claim 1, wherein the used nitrilation agent of cyanation is MCN, wherein M is a metal ion.
7. method as claimed in claim 6, wherein said nitrilation agent is KCN or NaCN.
8. the method for claim 1, wherein cyanation carries out in the presence of alkali.
9. method as claimed in claim 8, wherein said alkali are selected from pyridine, N-picoline, N-Methyl pyrrolidone, triethylamine, dimethylamine, K
2CO
3, Na
2CO
3Or its combination.
10. the method for claim 1 also comprises the step that each step reaction product is carried out separation and purification.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410057246 CN1740146A (en) | 2004-08-26 | 2004-08-26 | Prepn process of 2-fluoro-5-trifluoromethyl benzyl cyanide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410057246 CN1740146A (en) | 2004-08-26 | 2004-08-26 | Prepn process of 2-fluoro-5-trifluoromethyl benzyl cyanide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1740146A true CN1740146A (en) | 2006-03-01 |
Family
ID=36092699
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|---|---|---|---|
| CN 200410057246 Pending CN1740146A (en) | 2004-08-26 | 2004-08-26 | Prepn process of 2-fluoro-5-trifluoromethyl benzyl cyanide |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102372605A (en) * | 2011-08-02 | 2012-03-14 | 浙江永太科技股份有限公司 | Preparation method of 2-halogeno-5-trifluoromethyl benzyl alcohol |
| CN102381918A (en) * | 2011-08-31 | 2012-03-21 | 河南科技大学 | Method for synthesizing benzyl cyanide compound by using benzyl chloride compound |
| CN102924330A (en) * | 2012-09-03 | 2013-02-13 | 华东理工大学 | Method for large-scale preparation of 5-amino-1-naphthyl nitrile |
| CN103570499A (en) * | 2011-08-02 | 2014-02-12 | 浙江永太科技股份有限公司 | Preparation method of 2-halogenate-5-trifluoromethyl benzyl alcohol compound |
| CN103694135A (en) * | 2014-01-08 | 2014-04-02 | 浙江胡涂硅有限公司 | Purifying method of 2, 4, 5-triflorophenylacetonitrile |
-
2004
- 2004-08-26 CN CN 200410057246 patent/CN1740146A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102372605A (en) * | 2011-08-02 | 2012-03-14 | 浙江永太科技股份有限公司 | Preparation method of 2-halogeno-5-trifluoromethyl benzyl alcohol |
| CN103570499A (en) * | 2011-08-02 | 2014-02-12 | 浙江永太科技股份有限公司 | Preparation method of 2-halogenate-5-trifluoromethyl benzyl alcohol compound |
| CN102372605B (en) * | 2011-08-02 | 2014-03-05 | 浙江永太科技股份有限公司 | Preparation method of 2-halogeno-5-trifluoromethyl benzyl alcohol |
| CN103570499B (en) * | 2011-08-02 | 2016-04-13 | 浙江永太科技股份有限公司 | A kind of preparation method of 2-halogeno-5-trifluoromethyl benzyl alcohol |
| CN102381918A (en) * | 2011-08-31 | 2012-03-21 | 河南科技大学 | Method for synthesizing benzyl cyanide compound by using benzyl chloride compound |
| CN102381918B (en) * | 2011-08-31 | 2014-03-26 | 河南科技大学 | Method for synthesizing benzyl cyanide compound by using benzyl chloride compound |
| CN102924330A (en) * | 2012-09-03 | 2013-02-13 | 华东理工大学 | Method for large-scale preparation of 5-amino-1-naphthyl nitrile |
| CN103694135A (en) * | 2014-01-08 | 2014-04-02 | 浙江胡涂硅有限公司 | Purifying method of 2, 4, 5-triflorophenylacetonitrile |
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