CN1521154A - Process for preparing meta-trifluoromethyl benzyl alcohol - Google Patents
Process for preparing meta-trifluoromethyl benzyl alcohol Download PDFInfo
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- CN1521154A CN1521154A CNA031152317A CN03115231A CN1521154A CN 1521154 A CN1521154 A CN 1521154A CN A031152317 A CNA031152317 A CN A031152317A CN 03115231 A CN03115231 A CN 03115231A CN 1521154 A CN1521154 A CN 1521154A
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Abstract
The present invention discloses the preparation process of m-trifluoromethyl benzyl alcohol. M-trifluoromethyl benzyl halide capable of being mass produced and sodium acetate as one kind of industrial material are made to react to produce ester, which is acid or alkali hydrolyzed directly to obtain high purity m-trifluoromethyl benzyl alcohol in high yield. The present invention is one simple and safe industrial process.
Description
Technical field
The present invention relates to the preparation method of m-trifluoromethyl-benzyl-alcohol.
Background technology
M-trifluoromethyl-benzyl-alcohol is a kind of medicine, chemistry of pesticide intermediate, has in fields such as medicine, agricultural chemicals very to use widely.Mainly contain following several method preparation method at present:
(1) document J.A.C.S.72,149 (1950); J.O.C.24,38 (1959); J.O.C.25,733 (1960); Arzneimittlel.Forch.15 (10), 1251 (1965); Fr.2,199,458 (1974) and patent DE2,335,347, (1974) have disclosed a kind of method for preparing m-trifluoromethyl-benzyl-alcohol by Grignard reagent and formaldehyde reaction, the major defect that this method exists is that grignard reaction industrialization difficulty is big, and adopted low boiling point solvent, as ether etc., be difficult to suitability for industrialized production;
(2) document J.A.C.S74,4079, (1952) disclose the method that a kind of m-trifluoromethyl benzyl chloride and aqueous sodium carbonate back hydrolysis prepare m-trifluoromethyl-benzyl-alcohol, this method long reaction time, energy consumption height, efficient are low;
(3) document CollectionCzch.Chem.Cummuns.25,1199 (1960) have introduced the method that a kind of m-trifluoromethyl phenyl aldehyde and acetylene reaction prepare m-trifluoromethyl-benzyl-alcohol, have long reaction time equally, energy consumption height, inefficient defective;
(4) document J.O.C.45 (6), 951 (1980) have reported that a kind of m-trifluoromethyl benzene benzyl chloride photolysis prepares the method for m-trifluoromethyl-benzyl-alcohol, the difficult control of this method reaction, by product is many;
(5) J.O.C.42 (5), 858 (1977) have reported that the m-trifluoromethylbenzoic acid reduction prepares the method for m-trifluoromethyl-benzyl-alcohol, the as easy as rolling off a log suction of reductive agent that this method adopts, releasing hydrogen gas behind the chance water, inflammable and explosive;
(6) TetrahedronLett 29 (33), and 4057 (1988) have reported that a kind of document m-trifluoromethyl phenyl aldehyde reduction prepares the method for m-trifluoromethyl-benzyl-alcohol, the used prices of raw and semifnished materials height of this method, industrial difficult enforcement of catalyst system therefor;
(7) Ep206,951 have disclosed the method that a kind of document benzene benzylalcohol trifluoromethylation prepares m-trifluoromethyl-benzyl-alcohol, and the used bromotrifluoromethane of this method costs an arm and a leg, and side reaction is many, and product purity is low.
In sum, the method for still not having at present a kind of more satisfactory m-trifluoromethyl-benzyl-alcohol that is suitable for suitability for industrialized production.
Summary of the invention
The technical issues that need to address of the present invention are the methods that disclose a kind of new m-trifluoromethyl-benzyl-alcohol, to overcome the above-mentioned defective that prior art exists.
Technical conceive of the present invention is such: m-trifluoromethyl benzyl halogen and the industrial raw material acetic acid sodium reaction commonly used with industrial scale operation generates ester earlier, need not purifying and can carry out acidity or alkaline hydrolysis, can obtain the benzylalcohol of high purity, high yield, be very easy, a safety, be convenient to industrialized method.
Method of the present invention comprises the steps:
(1) condensation reaction of m-trifluoromethyl benzyl halogen and sodium acetate:
M-trifluoromethyl benzyl chloride and the sodium acetate that is dissolved in the solvent are reacted, and temperature of reaction is 80-150 ℃, and back flow reaction 3-12h is to reacting completely; Adopt conventional method from reaction product, to collect condenses then, product does not need purifying, be directly used in next step hydrolysis reaction, the solvent of being addressed is a kind of in acetate, methylsulfonic acid, phenylformic acid or the trifluoracetic acid, acetate preferably, the mol ratio of m-trifluoromethyl benzyl chloride and sodium acetate is 1: 1～10, and best is 1: 1.5～3;
The m-trifluoromethyl benzyl chloride of being addressed is the compound with following general structure:
Wherein: Z represents Cl, Br or I.
(2) hydrolysis reaction: with the reaction that is hydrolyzed of the aqueous solution of the condensation product of step (1) and alkalescence or acidic substance, back flow reaction 1～5 hour, best hydrolysis temperature is 40～70 ℃, adopt conventional method from reaction product, to collect hydrolyzate then, purity can reach more than 99.2%, and two step synthetic yields can reach more than 83%.
The alkaline matter of being addressed is alkali-metal oxyhydroxide, preferably NaOH or KOH, and the concentration of its aqueous solution is with 5%～30% for suitable, and the mol ratio of condensation product and alkali is:
1: 1～10, best is 1: 1.5～3;
The acidic substance of addressing are sulfuric acid or hydrochloric acid, and the concentration of its aqueous solution is suitable with 5%～30%, and condensation product with the mol ratio of acid is: 1: 1～10, and reaction expression is:
By above-mentioned disclosed technical scheme as seen, method of the present invention is easy and simple to handle, the reaction conditions gentleness, and side reaction is few, and the yield height is convenient to suitability for industrialized production.
Concrete aforesaid way
Embodiment 1
In the 1L there-necked flask of agitator, reflux condensing tube and thermometer is housed, add the sodium acetate of 200g (2.44ml) and the acetate of 250ml, and be heated to 80 ℃, drip the m-trifluoromethyl benzyl chloride of 292 grams (1.5ml) gradually, add and follow-up continuing be warming up to 120 ℃, backflow 8h is to reacting completely.Acetate is reclaimed in underpressure distillation.Add the 500ml water stratification then, organism is washed with 4*100ml, gets organism 312 grams, and productive rate 95.4%, product are very pure, do not need purifying, directly can be used for next step hydrolysis reaction;
Add the ester and 450 gram 15% alkaline solutions (2.25ml) that prepare above the 218.12g (1.0m.) in the 1L there-necked flask of agitator, reflux exchanger and thermometer is housed, mixture refluxed 3 hours, and the plate layer chromatography inspection reacts completely.Be cooled to room temperature then, with 370ml 6N hcl acidifying.The 4*8ml water washing of layering organic phase, organic product is through anhydrous MgSO
4Drying, then vacuum fractionation get 153 grams (100-103 ℃/18mm) product, productive rate 86.9%, purity 99.2%.Two step synthetic yields are: 82.9%.
Embodiment 2
In the 1L there-necked flask of agitator, reflux exchanger and thermometer is housed, add the sodium acetate of 200g (2.44ml) and the acetate of 250ml, and be heated to 150 ℃, the m-trifluoromethyl bromobenzyl that drips 1.5ml gradually is to reacting completely, and decompression steams acetate then.Add the 500ml water stratification, organism is washed with 4*100ml, gets organism 315 grams, productive rate 96.3%.Product is very pure, does not need purifying, directly can be used for next step hydrolysis reaction.
Add the ester and 450 gram 20% alkaline solutions (2.25ml) that prepare above the 218.1g (1.0m.) in the there-necked flask of the 1L that agitator, reflux exchanger and thermometer are housed, mixture is in 50 ℃ of stirring reactions, and plate layer chromatography inspection reaction is complete.Be cooled to room temperature then, use hcl acidifying.The layering organic phase washes with water, and organic product is through anhydrous MgSO
4Drying, vacuum fractionation is collected the cut of 100-103 ℃/18mm, gets product 156 grams, productive rate 88.6%, 99.5%, two step of purity synthetic yield is: 85.3%.
Embodiment 3
In the 1L there-necked flask of agitator, reflux exchanger and thermometer is housed, adds the sodium acetate of 200g (2.44ml) and the acetate of 500ml, and be heated to 65 ℃, drip the m-trifluoromethyl iodine benzyl of 1.5ml gradually, add and be warming up to 80 ℃, be incubated plate layer chromatography inspection in 6 hours, react complete.Be warming up to 150 ℃ again, with recovery part acetate, residue is cooled to room temperature, adds the 500ml water stratification, and organic layer 4*100ml water washing gets organism 303 grams, and thick productive rate 92.4% is not purified, is directly used in next step hydrolysis reaction;
Add the ester for preparing above the 218.1g (1.0m.) and 450 gram 10% alkaline solutions (2.25ml) in the there-necked flask of the 1L that agitator, reflux exchanger and thermometer are housed, mixture was in 60 ℃ of stirring reactions 4 hours, and plate layer chromatography inspection reaction is complete.Be cooled to room temperature then, with the 6N hcl acidifying of 370ml.The layering organic phase is with 4 ' 80ml water washing, through anhydrous MgSO
4Drying, the cut of 100-103 ℃/18mm is collected in underpressure distillation, gets product m-trifluoromethyl benzene benzylalcohol 132.6 grams, productive rate 75.3%, purity 99.0%.
Embodiment 4
According to the ester that embodiment 3 described operations generate, the hydrochloric acid with 15% stirred 5 hours at 50-80C °, used ethyl acetate extraction then, the extraction liquid anhydrous magnesium sulfate drying, and underpressure distillation gets 130 grams.
Claims (9)
1. the preparation method of a m-trifluoromethyl-benzyl-alcohol is characterized in that comprising the steps:
(1) m-trifluoromethyl benzyl chloride and the sodium acetate that is dissolved in the solvent are reacted, temperature of reaction is 80-150 ℃, and back flow reaction 3-12h adopts conventional method to collect condenses then from reaction product;
The m-trifluoromethyl benzyl chloride of being addressed is the compound with following general structure:
Wherein: Z represents Cl, Br or I.
(2) aqueous solution of the condensation product of step (1) and alkalescence or acidic substance is hydrolyzed reaction, back flow reaction 1～5 hour adopts conventional method to collect hydrolyzate then from reaction product.
2. method according to claim 1 is characterized in that the solvent of being addressed is a kind of or mixing acid in acetate, methylsulfonic acid, propionic acid, trifluoracetic acid, the phenylformic acid.
3. method according to claim 2 is characterized in that solvent is an acetate.
4. method according to claim 2 is characterized in that hydrolysis temperature is 40～70 ℃.
5. method according to claim 1 is characterized in that the alkaline matter of being addressed is alkali-metal oxyhydroxide, and the mol ratio of condensation product and alkali is: 1: 1～10.
6. method according to claim 5 is characterized in that alkaline matter is NaOH or KOH, and the mol ratio of condensation product and alkali is: 1: 1.5～3.
7. method according to claim 1 is characterized in that the acidic substance of addressing are sulfuric acid or hydrochloric acid, and condensation product with the mol ratio of acid is: 1: 1～10.
8. according to each described method of claim 1～7, the mol ratio that it is characterized in that m-trifluoromethyl benzyl chloride and sodium acetate is 1: 1～10.
9. method according to claim 8, the mol ratio that it is characterized in that m-trifluoromethyl benzyl chloride and sodium acetate is 1: 1.5～3.
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| CN 03115231 CN1283605C (en) | 2003-01-28 | 2003-01-28 | Process for preparing meta-trifluoromethyl benzyl alcohol |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101643390B (en) * | 2009-08-21 | 2011-11-09 | 上海赫腾高科技有限公司 | Preparation method of m-trifluoromethyl-benzyl-alcohol |
| 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 |
| CN114773147A (en) * | 2022-05-10 | 2022-07-22 | 浙江永太科技股份有限公司 | Preparation method of 2,4, 5-trifluorobenzyl bromide |
-
2003
- 2003-01-28 CN CN 03115231 patent/CN1283605C/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101643390B (en) * | 2009-08-21 | 2011-11-09 | 上海赫腾高科技有限公司 | Preparation method of m-trifluoromethyl-benzyl-alcohol |
| 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 |
| 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 |
| CN114773147A (en) * | 2022-05-10 | 2022-07-22 | 浙江永太科技股份有限公司 | Preparation method of 2,4, 5-trifluorobenzyl bromide |
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| CN1283605C (en) | 2006-11-08 |
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