Title of Invention

"A PROCESS FOR PRODUCING A HALOALKYL ETHER COMPOUND"

Abstract

A process for producing a haloalkyl ether compound of the formula (1) wherein a compound of the formula (2) is reacted with a compound of the formula (3) in the presence of a Lewis acid wherein R1 is straight-chain or branched alkyl having 1 to 4 carbon atoms, wherein R1 is straight-chain or branched alkyl having 1 to 4 carbon atoms, wherein R1 and X are as defined above; the lewis acid is A1X3, FeX3, SbX5, TeX2, SnX4, TiX4, TeX4, BiX3, ZnX2, SiX4 BX3 or P2O5, (X is Cl, Br or I); and the reaction temperature is -10°C to +50°C.

Full Text

TECHNICAL FIELD The present invention relates to a process for producing a haloalkyl ether compound BACKGROUND ART Haloalkyl ether compounds are usable as a starting material for an aromatic chloromethyl compound which is widely used as intermediates for medicals, dyes, ion-exchange resins, conductive agents, antistatic agents, etc. In recent years, haloalkyl ether compounds are usable as a starting material for a quaternary ammonium salt which is expected as an electrolyte for a electrochemical device such as a battery, capacitor, etc. As a method of preparing a haloalkyl ether compound, a method is conventionally known wherein an aldehyde, alchohol and hydrogen halide are reacted (nonpatent literature 1). However, this method entails many impurities such as aldehyde condensates, hyperreactants, etc., and has difficulty of obtaining a haloalkyl ether compound having high purity. Particularly in preparing chloromethyl methyl ether, cancer-causing bischloromethyl ether is produced in a large amount as a by-product, giving problems in handling and disposal thereof. In order to solve the above problems, for example, it is known to react a compound of the formula (2) with a compound of the formula (3) with heat to prepare a haloalkyl ether compound of the formula (1) (nonpatent literature 2). Although by-products are formed in a small amount in this method, the reaction is conducted at a high temperature (55 to 60° C) for a long period of time (18 hours). Thus, it is considered that a low-boiling starting material and highly toxic chloromethyl methyl ether (desired compound) will vaporize to burden the environment. [nonpatent literature 1] ORGANIC SYNTHESES Collective Volume 1 P.377-379 [nonpatent literature 2] J. Org. Chem. 1994, 59, 6499-6500 An object of the present invention is to provide a process for producing a haloalkyl ether compound at a low temperature, with a short reaction time and improved yield, and less likely to burden the environment. DISCLOSURE OF THE INVENTION The present invention provides the following inventions. 1. A process for producing a haloalkyl ether compound of the formula (1) wherein a compound of the formula (2) is reacted with a compound of the formula (3) in the presence of a Lewis acid (Figure Removed) wherein R1 is straight-chain or branched alkyl having 1 to 4 carbon atoms, wherein R2 is straight-chain or branched alkyl having 1 to 8 carbon atoms or phenyl, and X is a halogen atom(Figure Removed) wherein R1 and X are as defined above. In the present invention, examples of straight-chain or branched alkyl having 1 to 4 carbon atoms represented by R1 are methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl and tert-butyl. Preferable are straight-chain or branched alkyl having 1 to 3 carbon atoms. More preferable are methyl and ethyl. Examples of the compound of the formula (2) are dimethoxymethane, diethoxymethane, di-n-propoxymethane, di-iso-propoxymethane, di-n-butoxymethane, di-sec-butoxymethane and di-tert-butoxymethane. Preferable are dimethoxymethane, diethoxymethane, di-n-propoxymethane and di-iso-propoxymethane. More preferable are dimethoxymethane and diethoxymethane. Examples of straight-chain or branched alkyl having 1 to 8 carbon atoms represented by R2 are methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl , tert-butyl, n-pentyl, n-hexyl, n-heptyl and n-octyl. Preferable are straight-chain or branched alkyl having 1 to 5 carbon atoms. More preferable are straight-chain alkyl having 1 to 5 carbon atoms. Examples of halogen atoms represented by X are Cl, Br and I. Examples of the compound of the formula (3) are acetyl chloride, propionyl chloride, n-butyryl chloride, n-pentanoyl chloride, n-hexanoyl chloride, n-heptanoyl chloride, n-octanoyl chloride, n-nonanoyl chloride, benzoyl chloride, and bromides of these compounds. Preferable are acetyl chloride, propionyl chloride, n-butyryl chloride, n-pentanoyl chloride, n-hexanoyl chloride and benzoyl chloride. Conventionally known Lewis acids are widely usable. Examples of Lewis acids are A1X3, FeX3, SbX5, TeX2, SnX4, TiX4, TeX4, BiX3, ZnX2, SiX4, BX3, P2O5, (X is Cl, Br or I) . More specific examples thereof are titanium trichloride, titanium tetrachloride, molybdenum trichloride, molybdenum pentachloride, iron (IH) chloride, iron (IE) bromide, zinc chloride, zinc bromide, boron trifluoride, boron trifluoride ether complex, boron trichloride, boron tribromide, aluminum chloride, aluminum bromide, gallium (It) chloride, tin chloride, tin bromide, antimony trichloride, antimony pentachloride, bismuth (IE) chloride, bismuth (II and IV) bromide, silicon tetrachloride, tellurium (H and IV) chloride and phosphorus pentaoxide. Among them, iron (III) chloride and aluminum chloride are preferable in view of reaction selectivity and improved yield of the desired product. Lewis acids are usable singly, or at least two of them are usable. Examples of haloalkyl ether compound of the formula (1) are chloromethyl methyl ether, chloromethyl ethyl ether, chloromethyl-n-propyl ether, chloromethyl-iso-propyl ether, chloromethyl-n-butyl ether, chloromethyl-sec-butyl ether and chloromethyl-tert-butyl ether, and corresponding bromides of these compounds. Preferable are chloromethyl methyl ether, chloromethyl ethyl ether, chloromethyl-n-propyl ether and chloromethyl-iso-propyl ether. More preferable are chloromethyl methyl ether and chloromethyl ethyl ether. Typical of process for preparing haloalkyl ether compound of the formula (1) is explained by the following reaction equation. (1) The haloalkyl ether compound of the formula (1) can be prepared by reacting a compound of the formula (2) and a compound of the formula (3) in the presence of Lewis acid. The reaction is carried out without a solvent or in a suitable solvent. The solvent to be used can be a wide variety of known solvents insofar as they are capable of dissolving Lewis acid, the compounds of the formulas (2) and (3) and will not adversely affect the reaction. Examples of such solvents are hexane, heptane, cyclohexane and like aliphatic hydrocarbons, dichloromethane, chloroform and like hydrocarbon halides, acetone, methyl ethyl ketone and like ketones, methyl acetate, ethyl acetate and like esters, toluene and like aromatic hydrocarbons, acetonitrile and like nitriles. The compound of the formula (2) and the compound of the formula (3) are used in the ratio usually of 1.0 to 1.5 equivalents, preferably 1.0 to 1.2 equivalents of the latter based on the former. Lewis acid is used in an amount of preferably 0.0001 to 1 equivalent, more preferably 0.0001 to 0.1 equivalent, most preferably 0.001 to 0.1 equivalent based on the compound of the formula (2). When a large quantity of Lewis acid is used, a slurry of the reactants becomes a high concentration, the reaction is difficult to be controlled and the product is difficult to be purified, causing an increased loss of the desired product. Further, upon distillation, boiling point elevation occurred which causes thermal decomposition of the desired product, decrease in yield and purity of the desired product, etc., hence unfavorable. The reaction is carried out usually at -10 to +50° C, preferably at 0 to 30° C, more preferably at 0 to 10° C, for 10 minutes to 200 hours, preferably for 10 minutes to 10 hours, more preferably 0.5 to 5 hours. The desired product obtained by the foregoing reaction can be readily isolated from the reaction mixture and purified by usual isolating and purifying means such as distillation, concentration, organic solvent extraction, centrifuging, washing, chromatography and recrystallization. BEST MODE OF CARRYING OUT THE INVENTION The present invention will be described with reference to the following Examples, but is not limited to these examples. Example 1 To a vessel having an inside atmosphere replaced by nitrogen were added 0.02 g of anhydrous iron (ffi) chloride (reagent of Kishida Chemical Co., Ltd.) and 14.5 g of dimethoxymethane (reagent of Kanto Chemical Co., Inc.). Acetyl chloride (15.0 g, reagent of Kanto Chemical Co., Inc.) was added dropwise to the mixture at 3°C over a period of 1 hour. The mixture was stirred at,2°C for 1 hour to obtain the desired chloromethyl methyl ether (yield 100%). Yield was confirmed by 1H-NMR. ^-NMR (CDC13) (5ppm: 2.02(s 3Hb), 3.48(s 3Ha), 3.63(s 3Hb), 5.43(s 2Ha) Example 2 To a vessel having an inside atmosphere replaced by nitrogen were added 0.2 g of anhydrous iron (IH) chloride (same as above) and 14.5 g of dimethoxymethane (same as above). Acetyl chloride (15.0 g, same as above) was added dropwise to the mixture at 3°C over a period of 1.5 hours to obtain the desired chloromethyl methyl ether (yield 100%) Yield was confirmed by 1H-NMR. ^-NMR (CDC13) Oppm: 2.02(s 3Hb), 3.48(s 3Ha), 3.63(s 3Hb), 5.43(s 2Ha) Example 3 To a vessel having an inside atmosphere replaced by nitrogen were added 0.29 g of anhydrous iron (IE) chloride (same as above) and 14.1 g of dimethoxymethane (same as above). n-Hexanoyl chloride (25.0 g, reagent of Tokyo Kasei Co., Ltd.) was added dropwise to the mixture at 3°C over a period of 1 hour to obtain the desired chloromethyl methyl ether (yield 100%). Yield was confirmed by ^-NMR. ^-NMR (CDC13) 0.88(b 3Hb), 1.30(b 4Kb), 1.63(b 2Kb), 2.32(b 2Kb), 3.50(s 3Ha), 3.67(s 3Hb), 5.44(s 2Ha) Example 4 To a vessel having an inside atmosphere replaced by nitrogen were added 0.30 g of anhydrous iron (M) chloride (same as above) and 20.8 g of diethoxymethane (reagent of Tokyo Kasei Co., Ltd.). Acetyl chloride (15.7 g, same as above) was added dropwise to the mixture at 3°C over a period of 1 hour to obtain the desired chloromethyl methyl ether (yield 100%). Yield was confirmed by 1H-NMR. '-H-NMR (CDC13) Oppm: 1.27(m 3Ha&3Hb) , 2.08(s 3Hb), 3.77(q 2Ha), 4.15(q 2Kb), 5.52(s 2Ha) Example 5 To a vessel having an inside atmosphere replaced by nitrogen were added 0.29 g of anhydrous iron (HI) chloride (same as above) and 13.5 g of dimethoxymethane (same as above). Benzoyl chloride (25.0 g, reagent of Tokyo Kasei Co., Ltd.) was added dropwise to the mixture at 3°C over a period of 1 hour to obtain the desired chloromethyl methyl ether (yield 100%). Yield was confirmed by 1H-NMR. ^-NMR (CDC13) Oppm: 3.51(s 3Ha), 3.95(s 3Hb), 5.46(s 2Ha), 7.45(m 2Kb), 7.55(m 1Kb), 8.05(m 2Kb) Example 6 To a vessel having an inside atmosphere replaced by nitrogen were added 0.08 g of anhydrous aluminum (ffi) chloride (reagent of Wako Pure Chemical Ind. Ltd.) and 44.2 g of dimethoxymethane (same as above). Acetyl chloride (45.6 g, same as above) was added dropwise to the mixture at 3°C over a period of 0.5 hour. The mixture was stirred for 8 hours while gradually heating from 3°C to room temperature (25°C) to obtain the desired chloromethyl methyl ether (yield 94%). Yield was confirmed by 1H-NMR. ^-NMR (CDC13) 2.00(s 3Hb), 2.61(s 3Hd), 3.30(s 6Hc), 3.46(s 3Ha), 3.61(s 3Hb), 4.51(s 2Hc), 5.41(s 2Ha) Comparative Example 1 To a vessel having an inside atmosphere replaced by nitrogen was added 50.7 g of dimethoxymethane (same as above). Thereto was added acetyl chloride (52.3 g, same as above) dropwise at 3°C over a period of 1 hour. The mixture was stirred for 4 hours while gradually heating from 3°C to room temperature (25°C). The mixture was further heated to reflux (47°C) with stirring for 22 hours to obtain the desired chloromethyl methyl ether (yield 14%). Yield was confirmed by 1H-NMR. ^-NMR (CDC13) Oppm: 2.01(s 3Hb), 2.62(s 3Hd) , 3.31(s 6Hc), 3.47(s 3Ha), 3.62(s 3Hb), 4.53(s 2Hc), 5.42(s 2Ha) Comparative Example 2 To a vessel having an inside atmosphere replaced by nitrogen was added 14.1 g of dimethoxymethane (same as above). Thereto was added n-hexanoyl chloride (25.0 g, reagent of Tokyo Kasei Co., Ltd.) dropwise at 3°C over a period of 0.5 hour. The mixture was stirred for 4 hours while gradually heating from 3°C to room temperature (25°C). The mixture was further heated to reflux (66°C) with stirring for 22 hours to obtain the desired chloromethyl methyl ether (yield 7%). Yield was confirmed by 1H-NMR. ^-NMR (CDC13) 0.89(m 3Hb&3Hd) , 1.32(m 4Hb&4Hd), 1.70(m 2Hb&2Hd) , 2.29(t 2Kb), 2.86(t 2Hd) , 3.34(s 3Hc), 3.50(3 3Ha), 3.64(s 3Hb), 4.55(s 2Hc), 5.45(s 2Ha) Comparative Example 3 To a vessel having an inside atmosphere replaced by nitrogen was added 50.0 g of dimethoxymethane (same as above). Thereto was added benzoyl chloride (92.3 g, same as above) dropwise at 3°C over a period of 0.5 hour. The mixture was stirred for 4 hours while gradually heating from 3°C to room temperature (25°C) . The mixture was further heated to reflux (58°C) with stirring for 22 hours to obtain the desired chloromethyl methyl ether (yield 1%). Yield was confirmed by ^-NMR. Hl-NMR (CDC13) Oppm: 3.36(s 6Hc), 3.51(s 3Ha), 3.92(s 3Hb), 4.57(s 2Hc), 5.46( 2Ha), 7.52(m 2Hb&2Hd), 7.69(m IHb&lHd), 8.12(m 2Hb&2Hd) s INDUSTRIAL APPLICABILITY The process of the invention can provide a haloalkyl ether compound with a short reaction time and improved yield at a low temperature, and therefore greatly restricts vaporization of the haloalkyl ether compound which largely burden the environment. We claim 1. A process for producing a haloalkyl ether compound of the formula (1) wherein a compound of the formula (2) is reacted with a compound of the formula (3) in the presence of a Lewis acid (Formula Removed) wherein R1 is straight-chain or branched alkyl having 1 to 4 carbon atoms, (Formula Removed) wherein R2 is straight-chain or branched alkyl having 1 to 8 carbon atoms or phenyl, and X is a halogen atom, (Formula Removed) the lewis acid is A1X3, FeX3, SbX5, TeX2, SnX4, T1X4, TeX4, BiX3, ZnX2, SiX4, BX3 or P2O5, (X is Cl, Br or I); and the reaction temperature is -10°C to +50°C; wherein R1 and X are as defined above. 2. A process as claimed in claim 2 wherein Lewis acid is A1X3, FeX3, SbXs, S11X4, TiX4, ZnX2 or SiX4, (X is Cl, Br or I). 3. A process as claimed in claim 2 wherein Lewis acid is A1C13 or FeCl3. 4. A process as claimed in claim 3 wherein Lewis acid is FeCl3. 5. A process as claimed in claim 1 wherein Lewis acid is used in an amount of 0.0001 to 1 equivalent based on the compound of the formula (2).

Documents:

7287-DELNP-2007-Abstract-(17-11-2011).pdf

7287-delnp-2007-abstract.pdf

7287-delnp-2007-Claims (19-04-2012).pdf

7287-DELNP-2007-Claims-(17-11-2011).pdf

7287-delnp-2007-claims.pdf

7287-DELNP-2007-Correspondence Others-(04-08-2011).pdf

7287-DELNP-2007-Correspondence Others-(17-11-2011).pdf

7287-delnp-2007-Correspondence-others (19-04-2012).pdf

7287-delnp-2007-correspondence-others.pdf

7287-DELNP-2007-Description (Complete)-(17-11-2011).pdf

7287-delnp-2007-description (complete).pdf

7287-DELNP-2007-Form-1-(17-11-2011).pdf

7287-delnp-2007-form-1.pdf

7287-DELNP-2007-Form-2-(17-11-2011).pdf

7287-delnp-2007-form-2.pdf

7287-DELNP-2007-Form-3-(04-08-2011).pdf

7287-delnp-2007-form-3.pdf

7287-delnp-2007-form-5.pdf

7287-DELNP-2007-GPA-(17-11-2011).pdf

7287-delnp-2007-pct-301.pdf

7287-delnp-2007-pct-304.pdf

7287-delnp-2007-pct-308.pdf

7287-DELNP-2007-Petitio-137-(17-11-2011).pdf

abstract.jpg