CN102964218B - Process for preparing 4-methyl-2, 3, 5, 6-tetrafluorobenzyl alcohol - Google Patents
Process for preparing 4-methyl-2, 3, 5, 6-tetrafluorobenzyl alcohol Download PDFInfo
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Abstract
The invention discloses a process for preparing 4-methyl-2, 3, 5, 6-tetrafluorobenzyl alcohol. The process is characterized by comprising the steps: (1) reacting 2, 3, 5, 6-tetrafluorobenzyl alcohol with halogen hydride to obtain 3-halomethyl-1, 2, 4, 5-phenyl tetrafluoride; (2) carrying out hydrogenation, reduction and dehalogenation on 3-halomethyl-1, 2, 4, 5-phenyl tetrafluoride in the presence of a metal catalyst to obtain 2, 3, 5, 6-tetrafluorobenzene; and (3) in an inert solvent, reacting 2, 3, 5, 6-tetrafluorobenzene with an organic lithium reagent under low temperature to obtain an aryl lithium intermediate, and reacting the aryl lithium intermediate obtained with formaldehyde gas under low temperature to obtain 4-methyl-2, 3, 5, 6-tetrafluorobenzyl alcohol. The process has the advantages that the raw materials and the reagents are low in price and available, the reaction yield is good, the product purity is high and the like.
Description
Technical field:
The present invention relates to a kind of synthetic method of 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol, specifically, relate to one with 2,3,5,6-tetrafluorobenzyl alcohol for raw material, the method for synthesis 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol.
Background technology:
4-methyl-2,3,5,6-tetrafluorobenzyl alcohol is the key intermediate of the fluorine-containing pyrethroid insecticides tefluthrin of synthesizing efficient low toxicity.
The synthetic method of 4-methyl-2,3,5, the 6-tetrafluorobenzyl alcohol of bibliographical information is had to mainly contain following two kinds at present:
(1) with tetrafluoro terephthalyl alcohol for raw material, first through selective halogenation, obtain 4-monochloromethyl-2,3,5,6-tetrafluorobenzyl alcohol, then through reductive dehalogenation, obtain 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol, as CN1204104, CN101610988.
All there is the possibility of halogenation in two hydroxyls due to raw material tetrafluoro terephthalyl alcohol, therefore, the method inevitably has dihalo by product to generate in reaction process, causes reaction yield to decline, increases the difficulty of product purification simultaneously.
(2) with 1,2,4,5-tetra fluoro benzene for raw material, first, under butyllithium effect, with iodomethane reaction, 2 are obtained, 3,5,6-tetra-toluene fluoride, then under butyllithium effect, with carbon dioxide reaction, obtain 4-methyl-2,3,5,6-tetrafluorobenzoic aid, finally by lithium aluminium hydride reduction, obtain 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol, as GB2127013.
The method uses the methyl iodide of severe toxicity as methylating reagent, use costliness and the lithium aluminum hydride of danger as going back original reagent, operational condition is harsh, and synthesis cost is higher.
Summary of the invention:
The object of the present invention is to provide a kind of synthetic method of 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol of novelty, have raw material and reagent is cheap and easy to get, reaction yield is good, product purity advantages of higher.
The technical solution used in the present invention, a kind of synthetic method of 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol, is characterized in that:
Comprise following reactions steps:
(1) 2,3,5,6-tetrafluorobenzyl alcohol (I) and hydrogen halide react, and obtain 3-monochloromethyl-1,2,4,5-tetra fluoro benzene (II);
(2) 3-monochloromethyl-1,2,4,5-tetra fluoro benzene (II), under metal catalyst exists, through hydro-reduction dehalogenation, obtains 2,3,5,6-tetra-toluene fluoride (III);
(3) 2,3,5,6-tetra-toluene fluorides (III), in inert solvent, under low temperature, react with organolithium reagent, obtain lithium aryl intermediate; The lithium aryl intermediate of gained, in inert solvent, under low temperature, reacts with formaldehyde gas, obtains 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol (IV).
The synthetic route that the present invention adopts can represent with following reaction formula:
。
Arrange as follows further:
The synthetic method of a kind of 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol (IV) of the present invention, in synthesis step 1, described hydrogen halide be selected from hydrogenchloride, hydrogen bromide one or both.The existence form of hydrogen halide can be hydrogen halide, also can be hydrogen halide solution, if solution, and the aqueous solution of preferred corresponding hydrogen halide.The consumption of hydrogen halide is as the criterion to ensure that compound (I) fully reacts, and preferred hydrogen halide consumption is 1 ~ 10 times of the amount of substance of compound (I).Hydrogen halide in use, can according to reaction needed, disposable or join in reaction system in batches.
The synthetic method of a kind of 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol (IV) of the present invention, in synthesis step 1, reaction need be carried out in the presence of solvent.Solvent used is moisture single solvent or nonelectrolyte mixed aqueous solution.Use nonelectrolyte mixed aqueous solution time, in addition to water, other solvent composition is organic solvent, be selected from following one or more: the alkane solvents such as normal hexane, hexanaphthene, normal heptane, octane, the aromatic hydrocarbon solvents such as benzene,toluene,xylene; In mixed solvent, the volume ratio of water and organic solvent is 5:1 ~ 1:5.Solvent load is 1 ~ 10 times of compound (I) quality.
The synthetic method of a kind of 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol (IV) of the present invention, in synthesis step 1, preferred temperature of reaction is 50 ~ 120
oc.It should be noted that, reaction can be carried out under system reflux state, but due to system backflow, will speed up hydrogen halide and volatilize from reaction system, thus need more hydrogen halide just can react fully to carry out, therefore preferred temperature of reaction should lower than the reflux temperature of system.
The synthetic method of a kind of 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol (IV) of the present invention, in synthesis step 1, reaction can be carried out in atmospheric conditions, can also carry out under an increased pressure.React in atmospheric conditions, easily cause the volatilization loss of hydrogen halide, hydrogen halide consumption is increased and reaction times prolongation, but lower to the requirement of conversion unit.Carry out under an increased pressure, hydrogen halide volatilization loss can be avoided, thus reduce consumption and the Reaction time shorten of hydrogen halide, but to the corresponding raising of the requirement of conversion unit.When reacting under elevated pressure, reaction system pressure is preferably normal pressure to 0.5 MPa.
The synthetic method of a kind of 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol (IV) of the present invention, in synthesis step 2, described metal catalyst, is selected from one or more metals following: nickel, palladium, platinum.Metal catalyst can be elemental metals, also can be corresponding oxide compound, oxyhydroxide or salt, as palladous oxide, palladium hydroxide, platinum oxide, platinic hydroxide, nickelous chloride, Palladous chloride, platinum chloride etc.Catalyzer can appendix on suitable carrier, also can not use by appendix, available appendix carrier has gac, diatomite, aluminum oxide, silicon-dioxide etc., typically through the catalyzer of appendix as platinum charcoal, palladium charcoal.In addition, catalyzer is made hollow spongy structure, be also conducive to the catalytic activity improving catalyzer, typical hollow sponge catalyst is as Raney's nickel.Catalyst levels is 0.001 ~ 1 times of compound (II) quality, and preferred catalyst levels is 0.01 ~ 0.3 times of compound (II) quality.
The synthetic method of a kind of 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol (IV) of the present invention, in synthesis step 2, hydrogen source used is gaseous hydrogen.During reaction, the pressure of hydrogen is preferably normal pressure to 1 MPa.
The synthetic method of a kind of 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol (IV) of the present invention, in synthesis step 2, reaction need be carried out in the presence of solvent.Reaction solvent is polar protic solvent, as the lower alcohol of C1 ~ C4, the carboxylic acid of C1 ~ C4 and water.Preferred solvent be following one or more: methyl alcohol, ethanol, n-propyl alcohol, Virahol, acetic acid, propionic acid and water.Solvent load is 1 ~ 10 times of compound (II) quality.
The synthetic method of a kind of 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol (IV) of the present invention, in synthesis step 2, reaction process has hydrogen halide to generate.In order to reduce the impact of hydrogen halide on reaction, in reaction system, suitable acid binding agent can be added.Acid binding agent is optional from organic bases, mineral alkali and metal oxide, preferred acid binding agent be following one or more: triethylamine, Tri-n-Propylamine, diisopropyl ethyl amine, pyridine, DMAP, salt of wormwood, sodium carbonate, saleratus, sodium bicarbonate, potassium hydroxide, sodium hydroxide, magnesium oxide, calcium oxide, ferric oxide, zinc oxide.Acid binding agent consumption is 1 ~ 3 times of the amount of substance of compound (II).
The synthetic method of a kind of 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol (IV) of the present invention, in synthesis step 2, temperature of reaction is 0 ~ 100
oc, preferred temperature of reaction is 20 ~ 70
oc.
A kind of 4-methyl-2 of the present invention, 3,5, the synthetic method of 6-tetrafluorobenzyl alcohol (IV), in synthesis step 3, described inert solvent, be selected from following one or more: the ether solvents such as ether, isopropyl ether, methyl tertiary butyl ether, glycol dimethyl ether, tetrahydrofuran (THF), 2-methyltetrahydrofuran, the alkane solvents such as Skellysolve A, normal hexane, normal heptane, octane, the aromatic hydrocarbon solvent such as toluene, ethylbenzene.Solvent load is 1 ~ 10 times of compound (III) quality.
The synthetic method of a kind of 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol (IV) of the present invention, in synthesis step 3, described low temperature is-30 ~-90
oc.According to the actual needs of reaction, temperature of reaction, with the change of step of reaction, carries out necessary change in this temperature range, remains, improve reaction yield and product purity with the generation and raw material that reduce side reaction.
A kind of 4-methyl-2 of the present invention, 3,5, the synthetic method of 6-tetrafluorobenzyl alcohol (IV), in synthesis step 3, described organolithium reagent, be selected from following one or more: n-Butyl Lithium, isobutyl-lithium, s-butyl lithium, tert-butyl lithium, n-propyl lithium, isopropyl lithium, diisopropylamine lithium (LDA), LHMDS (LHMDS).The ratio of the amount of substance of organolithium reagent and compound (III) is: 1:1 ~ 1.5:1.Organolithium reagent can be made by oneself according to actual needs, and the solution being made into different concns uses, and conventional solvent has normal hexane and tetrahydrofuran (THF), also can select commercial standard standard commodities.Commercially available organolithium reagent is all the solution containing inert solvent, and has different concns specification available.Can the organolithium reagent of these different sizes, not affect smoothly significantly on reaction.The rate of addition of organolithium reagent is determined in the range of reaction temperature required to make temperature control in reaction system.
The synthetic method of a kind of 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol (IV) of the present invention, in synthesis step 3, described formaldehyde gas, be obtain after heating energy produces the precursor of formaldehyde gas, the formaldehyde gas obtained is using after drying.Produce the precursor of formaldehyde gas be selected from following one or more: paraformaldehyde, trioxymethylene, formalin.The ratio of the amount of substance of formaldehyde precursor and compound (III) is: 1:1 ~ 5:1.Formaldehyde gas directly can pass into reaction system, and the mode of also carrying by rare gas element enters reaction system.If adopted carrying mode, rare gas element used be selected from following one or both: nitrogen, helium.The speed that passes into of formaldehyde gas is determined in the range of reaction temperature required to make temperature control in reaction system.
Compared with prior art, its useful effect is embodied in the present invention:
(1) fundamentally avoid the selective problems of reactive group, reduce the generation of by product, reduce product purification difficulty, improve product purity and reaction yield;
(2) compound 2,3,5,6-tetra-toluene fluoride (III) is under highly basic effect, reacts and directly obtains product, avoid in prior art and first generate carboxylic acid, then by operations such as carboxylic acid reduction, reduce cost, simplify operation with formaldehyde gas.
Below in conjunction with embodiment, the invention will be further described.
Embodiment:
Embodiment one:
Add compound (I) 50 grams in 500 milliliters of reaction flasks, concentrated hydrochloric acid 140 grams, toluene 200 milliliters, stir and be warming up to 70
oc reacts 12 hours, and reaction system is cooled to room temperature, separates organic phase, and aqueous phase toluene 50 milliliters extraction 2 times, merges organic phase, and drying, concentrated, distillation, obtain compound (II, X=Cl) 50.3 grams.
Embodiment two:
Add compound (I) 36 grams in 500 milliliters of withstand voltage reactors, concentrated hydrochloric acid 40 grams, normal heptane 150 milliliters, confined reaction system, stir and be warming up to 100
oc reacts 7 hours, and reaction system is cooled to room temperature, separates organic phase, and aqueous phase ethyl acetate 50 milliliters extraction 2 times, merges organic phase, and drying, concentrated, distillation, obtain compound (II, X=Cl) 36.9 grams.
Embodiment three:
Add compound (I) 36 grams in 250 milliliters of reaction flasks, 48% hydrobromic acid aqueous solution 40 grams, toluene 200 milliliters, stir and heat up, reflux water-dividing separates to anhydrous, and reaction system, through concentrated, distillation, obtains compound (II, X=Br) 43.5 grams.
Embodiment four:
Add compound (I) 50 grams in 250 milliliters of reaction flasks, concentrated hydrochloric acid 250 grams, stir and be warming up to 50
oc reacts 20 hours, reaction system cool to room temperature, by ethyl acetate 100 milliliters of extracting twice, merges organic phase, and drying, concentrated, distillation, obtain compound (II, X=Cl) 49.6 grams.
Embodiment five:
Add compound (I) 40 grams in 500 milliliters of reaction flasks, 200 grams, water, dimethylbenzene 200 milliliters, stir and be warming up to 90
oc, leads to hydrogen chloride gas 1 hour through bubbling pipe in the mode of bubbling, insulation reaction, and after this every 1 hour, logical hydrogen chloride gas 15 minutes, is less than 0.5% to HPLC detection compound (I) content.Reaction system is cooled to room temperature, separates organic phase, and aqueous phase ethyl acetate 50 milliliters extraction 2 times, merges organic phase, and drying, concentrated, distillation, obtain compound (II, X=Cl) 41.3 grams.
Embodiment six:
In 500 milliliters of reaction flasks, add compound (II, X=Cl) 40 grams, palladium charcoal (10%) 4 gram, 24 grams, magnesium oxide, methyl alcohol 400 milliliters, reaction system uses nitrogen and hydrogen exchange gas three times respectively, and by hydrogen balloon hydrogen supply, stirs and be warming up to 50
oc reacts 10 hours.Reaction system is down to room temperature, crosses and filters insolubles, concentrating filter liquor, distillation, obtain compound (III) 31.3 grams.
Embodiment seven:
In 500 milliliters of reaction flasks, add compound (II, X=Br) 40 grams, Raney's nickel 12 grams, triethylamine 17 grams, ethanol 200 milliliters, reaction system uses nitrogen and hydrogen exchange gas three times respectively, and by hydrogen balloon hydrogen supply, stirs and be warming up to 70
oc reacts 10 hours.Reaction system is down to room temperature, crosses and filters insolubles, filtrate reduced in volume, add ethyl acetate 100 milliliters, 60 milliliters, water, stir 10 minutes, separate organic phase in residue, and drying, concentrated, distillation, obtain compound (III) 25.1 grams.
Embodiment eight:
In 500 milliliters of autoclaves, add compound (II, X=Br) 48.6 grams, platinum charcoal (5%) 0.5 gram, Virahol 250 milliliters, 55 grams, salt of wormwood, enclosed high pressure still, use nitrogen and hydrogen exchange system three times respectively, control hydrogen pressure 1 MPa, stir and be warming up to 40
oc reacts 8 hours.Reaction system is down to room temperature, crosses and filters insolubles, concentrating filter liquor, distillation, obtain compound (III) 31.2 grams.
Embodiment nine:
In 250 milliliters of autoclaves, add compound (II, X=Cl) 59.6 grams, palladium charcoal (5%) 3 gram, acetic acid 160 milliliters, enclosed high pressure still, use nitrogen and hydrogen exchange system three times respectively, control hydrogen pressure 0.5MPa, stirring at room temperature reacts 10 hours.Reaction system is crossed and is filtered insolubles, concentrating filter liquor, distillation, obtains compound (III) 45.9 grams.
Embodiment ten:
Add compound (III) 32.8 grams, anhydrous tetrahydro furan 150 milliliters in 500 milliliters of dry reaction flasks, stir under nitrogen protection and be cooled to-60 ~-70
oc, drips diisopropylamine lithium solution (2.0 mol/L) 150 milliliters, after dropwising, and temperature control-30 ~-40
oc stirring reaction 1 hour.Reaction system is cooled to-70 ~-80
oc, passes into formaldehyde gas (generated after adding thermal depolymerization by 30 grams of paraformaldehydes, and slowly brought into by nitrogen gas stream), logical Bi Houyu-50 ~-60
oc reacts 1 hour.Reaction system is risen again to room temperature, drips 100 milliliters, water, stirs a moment, filters, removing insolubles, and filtrate adjusts pH to acid with concentrated hydrochloric acid, with ethyl acetate 80 milliliters extraction 3 times, merges organic phase, and drying, concentrated, distillation, obtain compound (IV) 31.8 grams.
Embodiment 11:
Add compound (III) 41 grams, anhydrous diethyl ether 100 milliliters in 500 milliliters of dry reaction flasks, stir under nitrogen protection and be cooled to-70 ~-80
oc, drips n-butyllithium solution (1.6 mol/L) 160 milliliters, after dropwising, in-50 ~-60
oc stirring reaction 1 hour.Reaction system is cooled to-80 ~-90
oc, passes into formaldehyde gas (generated after adding thermal depolymerization by 15 grams of paraformaldehydes, and slowly brought into by nitrogen gas stream), logical Bi Houyu-40 ~-50
oc reacts 1 hour.Reaction system is risen again to 0
omore than C, drips 150 milliliters, water, stirs a moment, filters, removing insolubles, and filtrate separates organic phase, and aqueous phase ethyl acetate 100 milliliters extraction 2 times, merges organic phase, and drying, concentrated, distillation, obtain compound (IV) 39.7 grams.
Embodiment 12:
Add compound (III) 30 grams, dry toluene 300 milliliters in 500 milliliters of dry reaction flasks, stir under nitrogen protection and be cooled to-60 ~-70
oc, drips isobutyl-lithium solution (1.6 mol/L) 140 milliliters, after dropwising, continues stirring reaction 1 hour.Formaldehyde gas (generated after adding thermal depolymerization by 17 grams of paraformaldehydes, and slowly brought into by helium flow) is passed into, logical complete rear continuation reaction 2 hours in system.Reaction system is risen again to 0
omore than C, drips 150 milliliters, water, stirs a moment, filters, removing insolubles, and filtrate separates organic phase, and aqueous phase ethyl acetate 80 milliliters extraction 2 times, merges organic phase, and drying, concentrated, distillation, obtain compound (IV) 30.1 grams.
Embodiment 13:
Add compound (III) 40 grams, dry ethylene glycol dimethyl ether 150 milliliters in 500 milliliters of dry reaction flasks, stir under nitrogen protection and be cooled to-70 ~-80
oc, drips n-butyllithium solution (2.5 mol/L) 110 milliliters, after dropwising, in-60 ~-70
oc stirring reaction 1 hour.Formaldehyde gas (being generated after adding thermal depolymerization by 29 grams of paraformaldehydes) is slowly passed into, logical Bi Houyu-30 ~-40 in system
oc reacts 1 hour.Reaction system is risen again to room temperature, drips 120 milliliters, water, stirs a moment, filters, removing insolubles, and filtrate, with ethyl acetate 100 milliliters extraction 3 times, merges organic phase, and drying, concentrated, distillation, obtain compound (IV) 36 grams.
Claims (2)
1. the synthetic method of 4-methyl-2,3,5, a 6-tetrafluorobenzyl alcohol, is characterized in that, comprise following reactions steps:
(1) 2,3,5,6-tetrafluorobenzyl alcohol and hydrogen halide react, and obtain 3-monochloromethyl-1,2,4,5-tetra fluoro benzene;
(2) 3-monochloromethyl-1,2,4,5-tetra fluoro benzene, under metal catalyst exists, through hydro-reduction dehalogenation, obtains 2,3,5,6-tetra-toluene fluoride;
Described metal catalyst, be selected from following one or more: platinum charcoal, palladium charcoal, Raney's nickel, catalyst levels is 0.01 ~ 0.3 times of 3-monochloromethyl-1,2,4,5-tetra fluoro benzene quality;
(3) 2,3,5,6-tetra-toluene fluorides, in inert solvent, under low temperature, react with organolithium reagent, obtain lithium aryl intermediate; The lithium aryl intermediate of gained, in inert solvent, under low temperature, reacts with formaldehyde gas, obtains 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol.
2. a kind of 4-methyl-2 according to claim 1,3,5, the synthetic method of 6-tetrafluorobenzyl alcohol, is characterized in that: in synthesis step 1, described hydrogen halide be selected from hydrogenchloride, hydrogen bromide one or both, hydrogen halide consumption is 2,1 ~ 10 times of the amount of substance of 3,5,6-tetrafluorobenzyl alcohol.
3. the synthetic method of a kind of 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol according to claim 1, it is characterized in that: in synthesis step 1, solvent used is moisture mixed solvent, and solvent load is 1 ~ 10 times of 2,3,5,6-tetrafluorobenzyl alcohol quality.
4. a kind of 4-methyl-2 according to claim 3,3,5, the synthetic method of 6-tetrafluorobenzyl alcohol, is characterized in that: in synthesis step 1, when solvent is moisture mixed solvent, solvent composition is in addition to water organic solvent, be selected from following one or more: normal hexane, hexanaphthene, normal heptane, octane, benzene,toluene,xylene, the volume ratio of water and organic solvent is 5:1 ~ 1:5.
5. the synthetic method of a kind of 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol according to claim 1, it is characterized in that: in synthesis step 1, temperature of reaction is 50 ~ 120
oc.
6. the synthetic method of a kind of 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol according to claim 1, it is characterized in that: in synthesis step 2, hydrogen source used is gaseous hydrogen, and hydrogen pressure is normal pressure to 1 MPa.
7. a kind of 4-methyl-2 according to claim 1,3,5, the synthetic method of 6-tetrafluorobenzyl alcohol, is characterized in that: in synthesis step 2, solvent for use be selected from following one or more: methyl alcohol, ethanol, n-propyl alcohol, Virahol, acetic acid, propionic acid, water, solvent load is 3-monochloromethyl-1,1 ~ 10 times of 2,4,5-tetra fluoro benzene quality.
8. the synthetic method of a kind of 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol according to claim 1, it is characterized in that: in synthesis step 2, temperature of reaction is 20 ~ 70
oc.
9. a kind of 4-methyl-2,3,5 according to claim 1, the synthetic method of 6-tetrafluorobenzyl alcohol, it is characterized in that: in synthesis step 3, described inert solvent, be selected from following one or more: ether, isopropyl ether, methyl tertiary butyl ether, glycol dimethyl ether, tetrahydrofuran (THF), 2-methyltetrahydrofuran, Skellysolve A, normal hexane, normal heptane, octane, toluene, ethylbenzene, solvent load is 2,3,1 ~ 10 times of 5,6-tetra-toluene fluoride quality.
10. a kind of 4-methyl-2 according to claim 1,3, the synthetic method of 5,6-tetrafluorobenzyl alcohol, is characterized in that: in synthesis step 3, described organolithium reagent, be selected from following one or more: n-Butyl Lithium, isobutyl-lithium, s-butyl lithium, tert-butyl lithium, n-propyl lithium, isopropyl lithium, diisopropylamine lithium, LHMDS, organolithium reagent and 2,3, the ratio of the amount of substance of 5,6-tetra-toluene fluoride is: 1:1 ~ 1.5:1.
11. a kind of 4-methyl-2,3,5 according to claim 1, the synthetic method of 6-tetrafluorobenzyl alcohol, it is characterized in that: in synthesis step 3, described formaldehyde gas obtains after heating energy produces the precursor of formaldehyde gas, and the formaldehyde gas obtained is using after drying.
12. a kind of 4-methyl-2 according to claim 11,3, the synthetic method of 5,6-tetrafluorobenzyl alcohol, is characterized in that: in synthesis step 3, used can produce formaldehydogenic precursor, be selected from following one or more: paraformaldehyde, trioxymethylene, formalin, formaldehyde precursor and 2,3, the ratio of the amount of substance of 5,6-tetra-toluene fluoride is: 1:1 ~ 5:1.
The synthetic method of 13. a kind of 4-methyl-2,3,5,6-tetrafluorobenzyl alcohols according to claim 1, it is characterized in that: in synthesis step 3, temperature of reaction is-30 ~-90
oc.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1839113A (en) * | 2000-10-27 | 2006-09-27 | 辛甄塔有限公司 | Preparation of 4-methyl-2, 3, 5, 6-tetrafluorobenzyl alcohol |
| CN102731269A (en) * | 2012-07-04 | 2012-10-17 | 浙江中欣化工股份有限公司 | Synthesis method of 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1839113A (en) * | 2000-10-27 | 2006-09-27 | 辛甄塔有限公司 | Preparation of 4-methyl-2, 3, 5, 6-tetrafluorobenzyl alcohol |
| CN102731269A (en) * | 2012-07-04 | 2012-10-17 | 浙江中欣化工股份有限公司 | Synthesis method of 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol |
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