CN102964218A - 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 4-methyl-2,3,5, the synthetic method of 6-tetrafluorobenzyl alcohol, specifically, relating to a kind of is raw material with 2,3,5,6-tetrafluorobenzyl alcohol, synthetic 4-methyl-2,3,5, the method for 6-tetrafluorobenzyl alcohol.
Background technology:
4-methyl-2,3,5,6-tetrafluorobenzyl alcohol are the key intermediates of the fluorine-containing pyrethroid insecticides tefluthrin of synthesizing efficient low toxicity.
The 4-methyl-2,3,5 that bibliographical information is arranged at present, the synthetic method of 6-tetrafluorobenzyl alcohol mainly contain following two kinds:
(1) take the tetrafluoro terephthalyl alcohol as raw material, at first through selective halogenation, obtain 4-monochloromethyl-2,3,5, the 6-tetrafluorobenzyl alcohol again through reductive dehalogenation, obtains 4-methyl-2,3,5, the 6-tetrafluorobenzyl alcohol, such as CN1204104, CN101610988.
Because all there is the possibility of halogenation in two hydroxyls of raw material tetrafluoro terephthalyl alcohol, therefore, the method has the dihalo by product to generate in reaction process inevitably, causes reaction yield to descend, and increases simultaneously the difficulty of product purification.
(2) be raw material with 1,2,4,5-tetra fluoro benzene, at first under the butyllithium effect, with iodomethane reaction, obtain 2,3,5,6-tetrafluoro toluene is again under the butyllithium effect, with carbon dioxide reaction, obtain 4-methyl-2,3,5, the 6-tetrafluorobenzoic aid, finally by lithium aluminium hydride reduction, obtain 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol is such as GB2127013.
The method uses the methyl iodide of severe toxicity as methylating reagent, uses expensive and dangerous lithium aluminum hydride as going back original reagent, and operational condition is harsh, and synthetic cost is higher.
Summary of the invention:
The object of the present invention is to provide a kind of 4-methyl-2,3,5 of novelty, the synthetic method of 6-tetrafluorobenzyl alcohol has raw material and reagent is cheap and easy to get, and reaction yield is good, the product purity advantages of higher.
The technical solution used in the present invention, a kind of 4-methyl-2,3,5, the synthetic method of 6-tetrafluorobenzyl alcohol is characterized in that:
Comprise following reactions steps:
(1) 2,3,5,6-tetrafluorobenzyl alcohol (I) and hydrogen halide reaction obtain 3-monochloromethyl-1,2,4,5-tetra fluoro benzene (II);
(2) 3-monochloromethyl-1,2,4,5-tetra fluoro benzene (II) in the presence of metal catalyst, through the hydro-reduction dehalogenation, obtains 2,3,5,6-tetrafluoro toluene (III);
(3) 2,3,5,6-tetrafluoro toluene (III) under low temperature, with the organolithium reagent reaction, obtains the lithium aryl intermediate in inert solvent; The lithium aryl intermediate of gained under low temperature, with the formaldehyde gas reaction, obtains 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol (IV) in inert solvent.
The synthetic route that the present invention adopts can represent with following reaction formula:
Further arrange as follows:
A kind of 4-methyl-2,3,5 of the present invention, the synthetic method of 6-tetrafluorobenzyl alcohol (IV), in synthesis step 1, described hydrogen halide is selected from one or both in hydrogenchloride, the hydrogen bromide.The existence form of hydrogen halide can be hydrogen halide, also can be hydrogen halide solution, if solution, the aqueous solution of preferred corresponding hydrogen halide.The consumption of hydrogen halide with guarantee compound (I) fully reaction be as the criterion 1～10 times of the amount of substance that preferred hydrogen halide consumption is compound (I).Hydrogen halide in use can be according to reaction needed, disposable or join in the reaction system in batches.
A kind of 4-methyl-2,3,5 of the present invention, the synthetic method of 6-tetrafluorobenzyl alcohol (IV), in synthesis step 1, reaction needs to carry out in the presence of solvent.Used solvent is moisture single solvent or nonelectrolyte mixed aqueous solution.When using nonelectrolyte mixed aqueous solution, outside dewatering, 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 the 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.
A kind of 4-methyl-2,3,5 of the present invention, the synthetic method of 6-tetrafluorobenzyl alcohol (IV), in synthesis step 1, preferred temperature of reaction is 50～120
oC.Need to prove, reaction can be carried out under the system reflux state, but because system refluxes, will speed up hydrogen halide and volatilize from reaction system, carry out thereby need more hydrogen halide just can react fully, therefore preferred temperature of reaction should be lower than the reflux temperature of system.
A kind of 4-methyl-2,3,5 of the present invention, the synthetic method of 6-tetrafluorobenzyl alcohol (IV), in synthesis step 1, reaction can be carried out under condition of normal pressure, can also carry out under pressurized conditions.Under condition of normal pressure, react, easily cause the volatilization loss of hydrogen halide, so that the hydrogen halide consumption increases and the reaction times prolongs, but lower to the requirement of conversion unit.Under pressurized conditions, carry out, can avoid hydrogen halide volatilization loss, thereby reduce consumption and the Reaction time shorten of hydrogen halide, but to the corresponding raising that requires of conversion unit.Depress when reacting adding, reaction system pressure is preferably normal pressure to 0.5 MPa.
A kind of 4-methyl-2,3,5 of the present invention, the synthetic method of 6-tetrafluorobenzyl alcohol (IV), in synthesis step 2, described metal catalyst is selected from following one or more metals: nickel, palladium, platinum.Metal catalyst can be elemental metals, also can be corresponding oxide compound, oxyhydroxide or salt, such as palladous oxide, palladium hydroxide, platinum oxide, platinic hydroxide, nickelous chloride, Palladous chloride, platinum chloride etc.Catalyzer can appendix on suitable carrier, also appendix does not use, available appendix carrier has gac, diatomite, aluminum oxide, silicon-dioxide etc., typically through the catalyzer of appendix such as platinum charcoal, palladium charcoal.In addition, catalyzer is made the hollow spongy structure, also be conducive to improve the catalytic activity of catalyzer, the typical spongy catalyzer of hollow such 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.
A kind of 4-methyl-2,3,5 of the present invention, the synthetic method of 6-tetrafluorobenzyl alcohol (IV), in synthesis step 2, used hydrogen source is gaseous hydrogen.The pressure of hydrogen is preferably normal pressure to 1 MPa during reaction.
A kind of 4-methyl-2,3,5 of the present invention, the synthetic method of 6-tetrafluorobenzyl alcohol (IV), in synthesis step 2, reaction needs to carry out in the presence of solvent.Reaction solvent is the polar protic solvent, such as the lower alcohol of C1～C4, carboxylic acid and the water of C1～C4.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.
A kind of 4-methyl-2,3,5 of the present invention, the synthetic method of 6-tetrafluorobenzyl alcohol (IV), in synthesis step 2, reaction process has hydrogen halide to generate.In order to reduce hydrogen halide to the impact of reaction, can add suitable acid binding agent in the reaction system.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, yellow soda ash, saleratus, sodium bicarbonate, potassium hydroxide, sodium hydroxide, magnesium oxide, calcium oxide, ferric oxide, zinc oxide.The acid binding agent consumption is 1～3 times of amount of substance of compound (II).
A kind of 4-methyl-2,3,5 of the present invention, the synthetic method of 6-tetrafluorobenzyl alcohol (IV), 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 solvents such as toluene, ethylbenzene.Solvent load is 1～10 times of compound (III) quality.
A kind of 4-methyl-2,3,5 of the present invention, the synthetic method of 6-tetrafluorobenzyl alcohol (IV), in synthesis step 3, described low temperature is-30～-90
oC.According to the actual needs of reaction, temperature of reaction is carried out necessary change with the variation of step of reaction in this temperature range, and is residual with the generation and the raw material that reduce side reaction, improves reaction yield and product purity.
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 is made into the solution use of different concns, and solvent commonly used has normal hexane and tetrahydrofuran (THF), also can select commercially available standard specifications commodity.Commercially available organolithium reagent is the solution that contains inert solvent all, and has the different concns specification available.Can the organolithium reagent of these different sizes do not have significant impact smoothly on reaction.The rate of addition of organolithium reagent is so that the interior temperature control of reaction system comes definite in the range of reaction temperature that requires.
A kind of 4-methyl-2,3,5 of the present invention, the synthetic method of 6-tetrafluorobenzyl alcohol (IV), in synthesis step 3, described formaldehyde gas is to obtain after heating energy produces the precursor of formaldehyde gas, the formaldehyde gas that obtains is using after drying.The precursor that produces formaldehyde gas be selected from following one or more: Paraformaldehyde 96, trioxymethylene, formalin.The ratio of the amount of substance of formaldehyde precursor and compound (III) is: 1:1～5:1.Formaldehyde gas can directly pass into reaction system, also can enter reaction system by the mode that rare gas element carries.If adopted carrying mode, used rare gas element be selected from following one or both: nitrogen, helium.Formaldehyde gas pass into speed so that in the reaction system temperature control in the range of reaction temperature that requires, come to determine.
The present invention compared with prior art, its useful effect is embodied in:
(1) fundamentally avoids the selective problems of reactive group, reduced the generation of by product, reduced the product purification difficulty, improved product purity and reaction yield;
(2) compound 2,3,5, and 6-tetrafluoro toluene (III) directly obtains product with the formaldehyde gas reaction under the highly basic effect, avoided generating first carboxylic acid in the prior art, with operations such as carboxylic acid reduction, has reduced cost again, has simplified operation.
The invention will be further described below in conjunction with embodiment.
Embodiment:
Embodiment one:
Add compound (I) 50 grams in 500 milliliters of reaction flasks, concentrated hydrochloric acid 140 grams, 200 milliliters of toluene stir and are warming up to 70
oC reaction 12 hours, reaction system is cooled to room temperature, tells organic phase, and water merges organic phase with 50 milliliters of extractions of toluene 2 times, and drying, concentrated, distillation get 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, 150 milliliters of normal heptanes, the confined reaction system stirs and is warming up to 100
oC reaction 7 hours, reaction system is cooled to room temperature, tells organic phase, and water merges organic phase with 50 milliliters of extractions of ethyl acetate 2 times, and drying, concentrated, distillation get 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, 200 milliliters of toluene stir and heat up, and reflux water-dividing is to anhydrous telling, and reaction system gets compound (II, X=Br) 43.5 grams through concentrated, distillation.
Embodiment four:
Add compound (I) 50 grams in 250 milliliters of reaction flasks, concentrated hydrochloric acid 250 grams stir and are warming up to 50
oC reaction 20 hours, the reaction system cool to room temperature with 100 milliliters of extracting twice of ethyl acetate, merges organic phase, and drying, concentrated, distillation get compound (II, X=Cl) 49.6 grams.
Embodiment five:
Add compound (I) 40 grams in 500 milliliters of reaction flasks, water 200 grams, 200 milliliters of dimethylbenzene stir and are warming up to 90
oC, through bubbling pipe with the logical hydrogen chloride gas of the mode of bubbling 1 hour, insulation reaction, after this every 1 hour, logical hydrogen chloride gas 15 minutes, to HPLC detection compound (I) content less than 0.5%.Reaction system is cooled to room temperature, tells organic phase, and water merges organic phase with 50 milliliters of extractions of ethyl acetate 2 times, and drying, concentrated, distillation get 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, magnesium oxide 24 grams, 400 milliliters of methyl alcohol, reaction system is used respectively nitrogen and hydrogen exchange gas three times, and by the hydrogen balloon hydrogen supply, stirs and be warming up to 50
oC reaction 10 hours.Reaction system is down to room temperature, removes by filter insolubles, and concentrating filter liquor, distillation get 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, 200 milliliters of ethanol, reaction system is used respectively nitrogen and hydrogen exchange gas three times, and by the hydrogen balloon hydrogen supply, stirs and be warming up to 70
oC reaction 10 hours.Reaction system is down to room temperature, removes by filter insolubles, and filtrate decompression is concentrated, adds 100 milliliters of ethyl acetate in the residue, and 60 milliliters in water stirred 10 minutes, told organic phase, and drying, concentrated, distillation get 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, 250 milliliters of Virahols, salt of wormwood 55 grams, the enclosed high pressure still is used respectively nitrogen and hydrogen exchange system three times, and control hydrogen pressure 1 MPa stirs and is warming up to 40
oC reaction 8 hours.Reaction system is down to room temperature, removes by filter insolubles, and concentrating filter liquor, distillation get 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, 160 milliliters of acetic acid, the enclosed high pressure still is used respectively nitrogen and hydrogen exchange system three times, control hydrogen pressure 0.5MPa, stirring at room reaction 10 hours.Reaction system removes by filter insolubles, and concentrating filter liquor, distillation get compound (III) 45.9 grams.
Embodiment ten:
Add compound (III) 32.8 grams in the reaction flask of 500 milliliters of dryings, 150 milliliters of anhydrous tetrahydro furans stir under nitrogen protection and are 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 gram Paraformaldehyde 96s, and slowly brought into by nitrogen gas stream), logical Bi Houyu-50～-60
oC reaction 1 hour.Reaction system is risen again to room temperature, drips 100 milliliters in water, stirs a moment, filters, and removes insolubles, and filtrate transfers pH to acid with concentrated hydrochloric acid, with 80 milliliters of extractions of ethyl acetate 3 times, merges organic phase, and drying, concentrated, distillation get compound (IV) 31.8 grams.
Embodiment 11:
Add compound (III) 41 grams in the reaction flask of 500 milliliters of dryings, 100 milliliters of anhydrous diethyl ethers stir under nitrogen protection and are 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 gram Paraformaldehyde 96s, and slowly brought into by nitrogen gas stream), logical Bi Houyu-40～-50
oC reaction 1 hour.Reaction system is risen again to 0
oMore than the C, drip 150 milliliters in water, stir a moment, filter, remove insolubles, filtrate is told organic phase, and water merges organic phase with 100 milliliters of extractions of ethyl acetate 2 times, and drying, concentrated, distillation get compound (IV) 39.7 grams.
Embodiment 12:
Add compound (III) 30 grams in the reaction flask of 500 milliliters of dryings, 300 milliliters of dry toluenes stir under nitrogen protection and are cooled to-60～-70
oC drips isobutyl-lithium solution (1.6 mol/L) 140 milliliters, after dropwising, continues stirring reaction 1 hour.In system, pass into formaldehyde gas (generated after adding thermal depolymerization by 17 gram Paraformaldehyde 96s, and slowly brought into by helium flow), continue reaction 2 hours behind logical the finishing.Reaction system is risen again to 0
oMore than the C, drip 150 milliliters in water, stir a moment, filter, remove insolubles, filtrate is told organic phase, and water merges organic phase with 80 milliliters of extractions of ethyl acetate 2 times, and drying, concentrated, distillation get compound (IV) 30.1 grams.
Embodiment 13:
Add compound (III) 40 grams in the reaction flask of 500 milliliters of dryings, 150 milliliters of anhydrous glycol dimethyl ethers stir under nitrogen protection and are 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.In system, slowly pass into formaldehyde gas (after adding thermal depolymerization, being generated by 29 gram Paraformaldehyde 96s), logical Bi Houyu-30～-40
oC reaction 1 hour.Reaction system is risen again to room temperature, drips 120 milliliters in water, stirs a moment, filters, and removes insolubles, and filtrate merges organic phase with 100 milliliters of extractions of ethyl acetate 3 times, and drying, concentrated, distillation get compound (IV) 36 grams.
Claims (14)
1. 4-methyl-2,3,5, the synthetic method of 6-tetrafluorobenzyl alcohol is characterized in that, comprises following reactions steps:
(1) 2,3,5,6-tetrafluorobenzyl alcohol and hydrogen halide reaction obtain 3-monochloromethyl-1,2,4, the 5-tetra fluoro benzene;
(2) 3-monochloromethyl-1,2,4, the 5-tetra fluoro benzene in the presence of metal catalyst, through the hydro-reduction dehalogenation, obtains 2,3,5,6-tetrafluoro toluene;
(3) 2,3,5,6-tetrafluoro toluene under low temperature, with the organolithium reagent reaction, obtains the lithium aryl intermediate in inert solvent; The lithium aryl intermediate of gained under low temperature, with the formaldehyde gas reaction, obtains 4-methyl-2,3,5, the 6-tetrafluorobenzyl alcohol in inert solvent.
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 is selected from one or both in hydrogenchloride, the hydrogen bromide, the hydrogen halide consumption is 2,1～10 times of the amount of substance of 3,5,6-tetrafluorobenzyl alcohol.
3. 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 1, used solvent is moisture single solvent or moisture mixed solvent, and solvent load is 2,1～10 times of 3,5,6-tetrafluorobenzyl alcohol quality.
4. a kind of 4-methyl-2 according to claim 3,3, the synthetic method of 5,6-tetrafluorobenzyl alcohol is characterized in that: in synthesis step 1, when solvent is moisture mixed solvent, outside dewatering, mixed solvent consists of 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 are 5:1～1:5.
5. a kind of 4-methyl-2,3,5 according to claim 1, the synthetic method of 6-tetrafluorobenzyl alcohol is characterized in that: in synthesis step 1, temperature of reaction is 50～120
oC.
6. 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 2, described metal catalyst, be selected from following one or more: platinum charcoal, palladium charcoal, Raney's nickel, catalyst levels are 3-monochloromethyl-1,2,0.01～0.3 times of 4,5-tetra fluoro benzene quality.
7. a kind of 4-methyl-2,3,5 according to claim 1, the synthetic method of 6-tetrafluorobenzyl alcohol is characterized in that: in synthesis step 2, used hydrogen source is gaseous hydrogen, and hydrogen pressure is normal pressure to 1 MPa.
8. 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.
9. a kind of 4-methyl-2,3,5 according to claim 1, the synthetic method of 6-tetrafluorobenzyl alcohol is characterized in that: in synthesis step 2, temperature of reaction is 20～70
oC.
10. a kind of 4-methyl-2,3 according to claim 1,5, 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 are 2,3,1～10 times of 5,6-tetrafluoro toluene quality.
11. 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-tetrafluoro toluene is: 1:1～1.5:1.
12. a kind of 4-methyl-2,3 according to claim 1,5, the synthetic method of 6-tetrafluorobenzyl alcohol, it is characterized in that: in synthesis step 3, described formaldehyde gas is to obtain after heating energy produces the precursor of formaldehyde gas, and the formaldehyde gas that obtains is using after drying.
13. according to claim 1 with the described a kind of 4-methyl-2 of claim 12,3, 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 96, trioxymethylene, formalin, formaldehyde precursor and 2,3, the ratio of the amount of substance of 5,6-tetrafluoro toluene is: 1:1～5:1.
14. a kind of 4-methyl-2,3,5 according to claim 1, the synthetic method of 6-tetrafluorobenzyl alcohol 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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