CN1057753C - Phase transfer catalysis process synthesizing 2,2,2-trifluoroethyl difluoromethyl ether - Google Patents

Phase transfer catalysis process synthesizing 2,2,2-trifluoroethyl difluoromethyl ether Download PDF

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CN1057753C
CN1057753C CN98110813A CN98110813A CN1057753C CN 1057753 C CN1057753 C CN 1057753C CN 98110813 A CN98110813 A CN 98110813A CN 98110813 A CN98110813 A CN 98110813A CN 1057753 C CN1057753 C CN 1057753C
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preparation
alkyl
phase transfer
reaction
trifluoroethanol
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CN1197787A (en
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郭彩云
高敏
林永达
陈庆云
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Shanghai Institute of Organic Chemistry of CAS
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Shanghai Institute of Organic Chemistry of CAS
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Abstract

The present invention relates to a method for synthesizing 2, 2, 2-trifluoroethyl difluoromethyl ether by using 2, 2, 2-trifluoroethanol and monochlorodifluoro methane as raw materials at the existence of univalent metal hydroxide, water and organic solvents mixed with water at the co-catalysis of phase transfer agents and catalysts. The molar ratio of 2, 2, 2-trifluoroethanol, monochlorodifluoro methane, phase transfer agents and catalysts is 1:0.8 to 2:0.0005 to 0.02:0.001 to 0.1, wherein the phase transfer agents are crown ether compounds, quaternary ammonium salt, trialkylamine inorganic acid salt or strong alkaline trialkylamine, and the catalysts are trivalent phosphine or amine phosphorus compounds and potassium halide. The present invention has the advantages of simple and convenient method, high selectivity and high conversion rate.

Description

The phase transfer catalysis process Synthetic 2,2,2-trifluoroethyl difluoro methyl ether
The present invention relates to a kind of synthetic method of fluorine-containing ether, is Synthetic 2 under phase-transfer catalyst and catalyst action furtherly by 2,2,2 tfifluoroethyl alcohol and monochlorodifluoromethane, 2, and the synthetic method of 2-trifluoroethyl difluoro methyl ether.
2,2,2-trifluoroethyl difluoro methyl ether is a narcotic isofluranum and for the precursor compound of fluorine ether, is reacted in the presence of alkali by 2,2,2 tfifluoroethyl alcohol and monochlorodifluoromethane to make (U.S.P., 3,637,477,1972).In this synthetic method, form for making monochlorodifluoromethane: CF 2Cabbeen is placed on attention on the concentration or alkaline intensity that increases alkali, therefore, use solid caustic soda and anhydrous reaction system, transformation efficiency only about 30%, R.T.Terrell has used water, with the solubleness of the salt that increase to form, even use expensive 2,2, the 2-trifluoroethanol is as solvent, in autoclave with 3.7 mole 2,2, the 2-trifluoroethanol, 0.8 mole monochlorodifluoromethane, 1 moles of hydrogen potassium oxide and 1.4 mole of water, at 80-95 ℃ of reaction 2h, transformation efficiency is the highest also to have only 56%.So, also need the constantly simple synthesis of exploration high conversion.
The purpose of this invention is to provide a kind of is raw material from 2,2,2 tfifluoroethyl alcohol and monochlorodifluoromethane, high conversion and highly selective Synthetic 2 in the presence of the monovalence metal hydroxides, 2, the method for 2-trifluoroethyl difluoro methyl ether.
In synthetic method of the present invention, consider 2,2, the reaction of 2-trifluoroethanol and monochlorodifluoromethane, be the reaction between the solution-air phase, in the presence of the monovalence metal hydroxides, along with the carrying out of reaction, the concentration of the salt (NaCl and possible NaF) that forms increases gradually and precipitates, and gas-liquid-solid three-phase system occurred.In the reaction, must make monochlorodifluoromethane gas that bigger solubleness is arranged in liquid phase, adopt phase-transfer catalyst to help the carrying out that reacts.For fast reaction speed, select for use appropriate catalyst that reaction is finished with fast speeds.Selected for use water and with the mixed solvent of the organic solvent of water blend, with the salt that generates in the further solubilizing reaction process, impel reaction to carry out to the direction that favourable product generates.
Synthetic method of the present invention be monovalence metal hydroxides, water and with the organic solvent of water blend in the presence of, 2,2,2-trifluoroethanol, monochlorodifluoromethane, phase-transfer catalyst and catalyzer are at room temperature-100 ℃ reaction 2-10h, the Synthetic 2 of highly selective, high conversion, 2,2-trifluoroethyl difluoro methyl ether.The longer reaction times also is favourable to reaction, 40-80 ℃ of recommendation response temperature, reaction times 1-5h.
In the synthetic method of the present invention, 2,2, the mol ratio of 2-trifluoroethanol, monochlorodifluoromethane, phase-transfer catalyst and catalyzer is respectively 1: 0.8-2: 0.0005-0.02: 0.001-0.10, recommend mol ratio to be followed successively by 1: 1-1.5: 0.0006-0.002: 0.01-0.02.Described phase-transfer catalyst is a crown compound, quaternary ammonium salt, tertiary amine inorganic acid salt and alkaline tertiary amine.Crown compound is the crown compound that contains 4-10 oxygen, as 12 crown ethers-4, and 15-crown ether-5, hexaoxacyclooctadecane-6-6, heptaoxacycloheneicosane-7-7,30 crown ether-10 etc.Quaternary ammonium salt, tertiary amine inorganic acid salt, strong alkaline tertiary amine have following molecular formula: R 1R 2R 3NR 4X, R 1R 2R 3NHX, [CH 3(OCH 2CH 2) n] 3N, wherein R 1, R 2Or R 3=C 1-18Alkyl, phenyl, benzyl, R 4=C 1-4Alkyl, benzyl, phenyl, X=Cl, Br or I, n=1-3.Described catalyzer is trivalent phosphine or amine phosphorus compound, and molecular formula is (R 5) 3P, and potassium halide, wherein R 5=C 4-12Alkyl, phenyl, benzyl, (R 6) 2N, R 6=C 1-4Alkyl.
Adopt method of the present invention, can use monovalence metal hydroxides, water respectively, also can use the monovalence metal hydroxides aqueous solution.The mol ratio of 2,2,2 tfifluoroethyl alcohol and monovalence metal hydroxides is 1: 1-4, recommending mol ratio is 1: 2-3.Usually the concentration of aqueous solution of alkali adopts 20% to 60%, if be lower than 20%, in the reaction micro-CF can take place 3H gas and by product (CF 3CH 2O) 3CH (2-6%).
The mixed solvent of the organic solvent of water and blend among the present invention, the aqueous solution is 0.5-5 with the volume of organic solvent ratio: 1, can change to some extent by the concentration of solvent property and monovalence metal hydroxides.
Adopt synthetic method of the present invention, used organic solvent is the organic solvent with the water blend, as acetonitrile, and dioxane, tetrahydrofuran (THF), 2,2,2 tfifluoroethyl alcohol, diethylene glycol monomethyl ether, diethylene glycol dimethyl ether, dimethyl sulfoxide (DMSO), acetone, N, N dimethyl formamide, N-Methyl pyrrolidone etc.In order to get rid of side reaction, the alcohols with the water blend except 2,2,2 tfifluoroethyl alcohol is excluded.
Adopt synthetic method of the present invention, not only can in general reaction flask or jar, realize, and can in autoclave, finish.When adopting reaction flask or jar, monochlorodifluoromethane constantly feeds in the reaction system under reaction conditions.Adopt method of the present invention, not only method is easy, and transformation efficiency and selectivity height, common transformation efficiency 〉=80%, selectivity 〉=95%.
To help to understand the present invention by following embodiment, but not place restrictions on content of the present invention.
Embodiment 1
On three mouthfuls of reaction flasks of 1000ml, HCF is housed 2The Cl ingress pipe, thermometer, reflux exchanger is put into NaOH or the KOH aqueous solution 200-600g of 25-60 ℃ of %, CF successively 3CH 21.0 moles of OH, (C 8H 17) 3NCH 3Cl or (C 8H 17) 2C 6H 4CH 2NCH 3Br 0.1-0.5g, [(C 2H 5) 2N] 3P or (C 8H 17) 3P 2-4g and dioxane or acetonitrile 100-300ml, heated and stirred to 40 ℃, logical N 2Behind the gas, feed HCF 2Cl with the about 2-6h of 10-15g/h speed, bathes warm 50-60 ℃, and the exothermic heat of reaction reacting liquid temperature is up to 70 ℃.Then reduce to below 50 ℃, distillation is finished in reaction, collects bP＜33 ℃, about 88g.Purity 〉=96%, transformation efficiency 〉=80%, productive rate 72-75%.With this product low-temperature distillation, collect bP.29 ℃, content 99%, analytical data:
19F-NMR，ppm：-0.82(S，3F)，+10.3(d，2F)
1H-NMR，ppm：+6.24(t，1H)，+4.38(q.2H)
m/e： 51(HCF 2 +，100％)，83(CF 3CH 2 +，45.3％)，81(HCF 2OCH 2 +，30.5％)，
69(CF 3 +，21.42％)，131(M +-F，2.95％)，149(M +-H，0.26％).
Embodiment 2
In the 500ml autoclave, put into 50%KOH or the LiOH solution of 80-400g, acetonitrile or di-alcohol dme 50-400ml, three iso-octyl phosphines or three (dimethyl amine) phosphine 1-2g, (C 4H 9) 4NBr 0.1-0.15g and CF 3CH 2OH 50g finds time in the time of-78 ℃, with liquid HCF 2Cl 60g gradation is pressed in the still, and reaction is 2-3 hour in the time of 60-75 ℃, collects bP≤33 ℃ cut 96g, purity 〉=95%, transformation efficiency 85%, productive rate 〉=75%.
Embodiment 3
With 400g 50%KOH, 100g CF 3CH 2OH, 0.25g (C 4H 9) 4NBr, 1.8g KBr or KI and acetonitrile or acetone 200ml feed HCF gradually continuously when bathing warm 50 ℃ 2Cl 86.5g, 4h altogether.Distill after the reaction bP＜33 ℃ product 86g, purity 96%, transformation efficiency 82%, productive rate 75%.
Adopt the autoclave reaction under the same conditions, come to the same thing.
Embodiment 4
KOH aqueous solution 400g with 50%, CF 3CH 2OH, 100g (1.0mol), (CH 3OCH 2CH 2OCH 2CH 2) 3N0.25g or hexaoxacyclooctadecane-6-6 or 30-crown ether-10 0.2g, KBr 1.8g and acetonitrile 200ml, 3-4h feeds HCF continuously in the time of 50 ℃ 2Cl is 95.2g (1.1mol) altogether, stopped reaction, and distillation is collected＜33 ℃, 83g, purity 94%, transformation efficiency＞79%, productive rate 76%.
Embodiment 5
In reaction flask, with 100g CF 3CH 2OH, 0.85-1.2 mole HCF 2Cl, 50%NaOH or KOH aqueous solution 100ml, the 100ml-200ml organic solvent changes solvent, catalyzer, consisting of phase-transferring agent, in the time of 50-80 ℃, reaction 4-8h, result such as following table, wherein selectivity is all at 94-96%, transformation efficiency with 19FNMR result calculates.HCF 2Mol ℃ of h % of Cl alkali solvent phase transfer agent catalyst temperature time conversion ratio productive rate % 1.2 KOH dioxane // 70-80 8 25 50 1.2 KOH dioxane (C8H 17) 3NHCl/70-80 8 35 51 0.85 KOH dioxane (C 8H 17) 3NHCl (Et 2N) 3P 50-60 4 80 72 1.2 KOH diethylene glycol dimethyl ether (C 8H 17) 3NHCl/70-80 8 40 56 1.0 KOH CH 3CN (C 4H 9) 4NBr KBr 60-70 5 82 75 1.1 KOH CH 3CN (C 4H 9) 3NHBr KI 60-70 5 78 73 1.0 KOH CH 3CN (CH 3OCH 2CH 2OCH 2CH 2) 3NKBr 60-70 4 70 75 1.0 NaOH CH 3CN (C 2H 5) 3NCH 2C 6H 3Br KI 60-70 4 80 75 1.0 LiOH CH 3CH 2OH (C 2H 3) 3NCH 2C 6H 3Br KI 60-70 4 84 77

Claims (7)

1, a kind of 2,2, the preparation method of 2-trifluoroethyl difluoro methyl ether, comprise from 2,2,2-trifluoroethanol and monochlorodifluoromethane are raw material, monovalence metal hydroxides and water and with the mixed solvent of the organic solvent of water blend in reacting by heating, it is characterized in that adopting phase-transfer catalyst and catalyzer, described 2,2, the 2-trifluoroethanol, monochlorodifluoromethane, phase-transfer catalyst and catalyzer be reaction 2-10h when room temperature-100 ℃, and mol ratio is followed successively by 1: 0.8-2: 0.0005-0.02-0.001-0.1, described phase-transfer catalyst is a crown compound, quaternary ammonium salt, tertiary amine inorganic acid salt or strong alkaline tertiary amine, described catalyzer are trivalent phosphine or amine phosphorus compound, potassium halide.
2, preparation method as claimed in claim 1 is characterized in that described crown compound is the crown compound that contains 4-10 oxygen.
3, preparation method as claimed in claim 1 is characterized in that described quaternary ammonium salt, tertiary amine inorganic acid salt or strong alkaline tertiary amine are R 1R 2R 3NR 4X, R 1R 2R 3NHX, [CH 3(OCH 2CH 2) n] 3N, wherein R 1, R 2Or R 3=C 1-18Alkyl, phenyl, benzyl, R 4=C 1-4Alkyl, benzyl or phenyl, X=Cl, Br or I, n=1-3.
4, preparation method as claimed in claim 1 is characterized in that described trivalent phosphine or trivalent amine phosphorus compound have (R 5) 3P molecular formula, wherein R 5=C 4-12Alkyl, phenyl, benzyl or (RR 6) 2N, R 6=C 1-4Alkyl.
5, want 1 described preparation method as right, it is characterized in that described and the organic solvent water blend are acetonitriles, acetone, dioxane, 2,2,2 tfifluoroethyl alcohol, diethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran (THF), dimethyl sulfoxide (DMSO), N, N dimethyl formamide and N-Methyl pyrrolidone.
6, preparation method as claimed in claim 1 is characterized in that the oxyhydroxide mol ratio of described 2,2,2 tfifluoroethyl alcohol and monovalence metal is 1: 1-4.
7, preparation method as claimed in claim 1 is characterized in that described monovalence metal hydroxides is the aqueous solution that contains the monovalence metal hydroxides of 20-60%.
CN98110813A 1998-04-28 1998-04-28 Phase transfer catalysis process synthesizing 2,2,2-trifluoroethyl difluoromethyl ether Expired - Fee Related CN1057753C (en)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0892145A (en) * 1994-09-22 1996-04-09 Agency Of Ind Science & Technol Production of 1,2,2,2-tetrafluoroethyl trifluoromethyl ether
EP0706506A1 (en) * 1993-06-30 1996-04-17 E.I. Du Pont De Nemours And Company Fluorinated bis-ethers and process for preparing them and fluorinated methyl ethers

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0706506A1 (en) * 1993-06-30 1996-04-17 E.I. Du Pont De Nemours And Company Fluorinated bis-ethers and process for preparing them and fluorinated methyl ethers
JPH0892145A (en) * 1994-09-22 1996-04-09 Agency Of Ind Science & Technol Production of 1,2,2,2-tetrafluoroethyl trifluoromethyl ether

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