IL149339A - Imidazolium compounds, processes for their preparation and their use as ionic liquids in chemical reactions - Google Patents

Description

New imidazolium compounds, processes for their preparation and their use as ionic liquids in chemical reactions 1. Chemada Fine Chemicals Company (1996) 011X 0>bp»a yttt'a .1 (1996) Ltd. aia^ m-jano^ia N .2 2. Ben Gurion University of the Negev C.137643 - 1 - 149339/2 NEW IMIDAZOLIUM COMPOUNDS, PROCESSES FOR THEIR PREPARATION AND THEIR USE AS IONIC LIQUIDS IN CHEMICAL REACTIONS FIELD OF THE INVENTION This invention relates to imidazolium compounds, processes for their production and their use as ionic liquids in chemical reactions.

BACKGROUND OF THE INVENTION In recent years the use of ionic liquids as reaction medium in synthesis and catalysis has grown. Ionic liquids are typically used in reactions such as hydrogenations, dimerizations, polymerizations, as medium in electrochemical reactions and as extraction solvents. Ionic liquids are liquids composed entirely of ions. Usually, the term ionic liquid is used to describe all materials, which are liquids at temperature below a 100°C or even below 60°C. In some cases the ionic liquids may be a fluid at temperatures below 30°C. Examples of such low temperature ionic liquids or molten salts are described in several review articles (Room temperature ionic liquids. Solvents for synthesis and catalysis, Welton T., Chem. Rev. 1999, 99, 2071; Ionic liquids J. D. Holbrey, K. R. Seddon; Clean products and processes, 1999, 1, 223.) WO 95/21,871 describes an ionic liquid composed of a dialkylsubstituted imidazolium halide where the alkyl group has 6 or more carbon atoms, their preparation and use. The dialk l imidazolium halide salts, upon mixing with metal salts such as A1C13, form ionic liquids. WO 95/21,872 describes ionic liquid composed 25 of a ternary melt of a substituted imidazolium halide or substituted pyridinium halide, a quaternary aluminum or gallium salt and a quaternary ammonium salt, their preparation and use. WO 97/02252 describes the preparation of hydrophobic ionic liquids comprised of substituted pyridinium, imidazolium, pyrazolium, oxazolium, and other nitrogen containing heterocycles as cations and fluorine containing anions. It - 2 - 149339/3 should be noted that the different substituents on the cationic and anionic counterparts dictate the chemical nature and physical properties of the ionic liquid, e.g. acidic, neutral, hydrophobic or hydrophilic. For example, the reaction of alkyl methyl imidazolium chloride with HPF6 in water yields the hydrophobic ionic liquid [alkyl methyl imidazolium]PF6-, which being insoluble in water forms a new phase in the reaction mixture. Not every conceivable substituent or counterion may be used, and different substituents give rise to different ionic liquids, which vary in their potential use. Some may be efficient for one sort of reaction while inefficient for a different reaction. Thus a careful analysis of each ionic liquid should be done prior to its use as a medium for catalysis or synthesis. One way to tackle this variability in the properties of the various ionic liquids is the preparation of an array of ionic liquids for combinatorial screening of properties (Murphy, V.; Hagemeyer, A.; Poojaray, D. M.; WO 00/32572).

In addition, WO 01/77081 describes a vacuum procedure for the generation of the imidazolium carbene in 90-95% yield from an imidazolium chloride that does not require solvents, filtrations, or lead to the production of noxious waste products. The resultant products of this procedure can be separated to using any known separation techniques such as distillation.

SUMMARY OF THE INVENTION The present invention is based on the findings of a new family of compounds and the fact that may be used as ionic liquids. The new family comprises benzyl imidazolium cations with an appropriate anion.

Thus the present invention deals with a compound of formula (I): where R is a linear or branched C3-Ci0-alkyl, phenyl, benzyl which may optionally be substituted by alkyl or halogen, R1 is hydrogen, halogen, group, alkyloxy group, R2 is hydrogen, R3 is hydrogen or Ci-4-alkyl. X is a halogen, AICI4", BF4", PF6", [(CF3S02)2N]-, P04-3, HP04-2.

It is a further object of the present invention to provide methods for the preparation of the compounds of formula (I). The compounds of formula (I) may be prepared either by reacting benzylimidazole compounds with primary and/or secondary alkyl halides or by reacting alkylimidazole with the appropriately substituted benzyl halide.

It is yet a further object of the present invention to use the compounds of formula (I) as ionic liquids, which are used as reaction medium in chemical synthesis and catalysis.

DETAILED DESCRIPTION OF THE INVENTION The present invention deals with a new family of compounds. The compounds of the present invention are salts, which have low melting points, thus such compounds may serve as ionic liquids. The compounds of the present invention have a benzyl as one of the substituents of an imidazole moiety, which in turn serves as the quaternary salt component of the ionic liquid. The compounds of the present invention have the following advantages: They are easily prepared from readily available raw materials: benzylimidazole and primary and/or secondary alkyl halides. Alternatively, they may be prepared from readily available alkylimidazole with an appropriate substituted benzyl halide. Accordingly, the imidazolium halides of the present invention can be prepared by the following methods: By reaction of alkyl imidazoles with the appropriately substituted benzyl bromide for instance 1-benzy 1-3 -butyl imidazolium bromide can be prepared by reacting benzyl bromide with 1-butylimidazole. Alternatively the above mentioned 1-benzy 1-3 -butylimidazolium bromide can be prepared by reacting the benzyl imidazole with butyl bromide under the same conditions. In the latter case, due to the fact that benzylimidazole is a solid, the reaction can be performed in an appropriate solvent such as benzene, toluene, chloroform or trichloroethane. Another synthetic route, which does not require the use of an auxiliary solvent, is carried out by melting benzylimidazole at 70-80°C and adding to the melt an alkyl halide.

The ionic liquids of the present invention may be utilized as a medium for carrying out chemical reactions or as catalysts for such reactions. Non limiting examples for such chemical reactions are halogenations, hydrogenations, reductions, hydroformylation, alkoxycarbonylation, polymerizations and dimerizations. In particular they may be useful in reduction of carbonyls with NaBH e.g. Reformatsky reaction.

Examples Example 1: l-Benzyl-3-methylimidazolium bromide [Bzmim][Br] The salt was prepared using the method described for [bmim][Cl] (Huddleston, Chem. Commun., 1998, 1765). The reaction was highly exothermic. 1-methylimidazole (0.06 mole, 5.175 gr) was added very slowly to benzyl bromide (0.06 mole, 10.78 gr) at such a rate as to keep the temperature under 65°C. The product [Bzmim][Br], is slightly orange and crystalline at room temperature. Yield almost 100%. The Ή NMR spectrum (Bruker 500 MHz) for [Bzmim][Br] (d-chlroform, ppm) consist of the following peaks: δ 4.02 (s, N-CH3, 3H), 5.58 (s, N-CH2, 2H), 7.33 (m, phenyl-H, 3H), 7.50 (m, H 4,5 and phenyl-H, 3H), 7.62 (s, H 4,5, 1H), 10.12 (s, H 2, 1H).

Example 2: l-Benzyl-3-methylimidazolium hexafluorophosphate [Bzmim][PF6] [Bzmim][Br] (0.03 mole, 8gr) was transferred to a 0.5 L plastic container followed by the addition of 75 ml of deionized water. An aqueous solution of 60-65% HPF6 in a 1.2:1 molar ratio was added slowly at such a rate as to keep the temperature under 65°C. The product precipitated as a waxy solid after stirring for two hours and was collected by filtration. The solid obtained was washed several times by deionized water until the pH of the filtrate was 7. The wet [Bzmim][PF6] was dried at room temperature in a vacuum oven for 24 Hr. The product was obtained as a white powder (m.p = 146-148°C). The Ή NMR spectrum (Bruker 500 MHz) for [Bzmim][PF6] (d-acetone, ppm) consist of the following peaks: δ 4.04 (s, N-CH3, 3H), 5.55 (s, N-CHZ, 2H), 7.43 (m, phenyl-H, 5H), 7.70 (d, H 4,5, 2H), 9.07 (s, H 2, 1H).

IR (KBr plate): v/cm-l 3170, 3120 (s, aromatic C-H stretch), 1578, 1462, 1168 (s, sym. ring stretch).

Example 3: l-Benzyl-3-methylimidazolium tetrafluoroborate [Bzmim][BF4] [Bzmim][Br] (0.036 mole, 9.22gr) was transferred to a 0.5 L plastic container followed by the addition of 55 ml of deionized water. Three portions of NaBF4 salt in a 1.2:1 total molar ratio was added. The tetrafluoroborate salt immediately separate from the aqueous phase. After stirring the mixture for two hours, it was extracted by 3 portions of 50 ml of dichloromethane(pH =6 in the water phase) . The organic layer was collected, dried over CaCl2, filtered and the solvent removed in vacuo to yield the tetrafluoroborate salt as a crystalline oily liquid that solidify at room temperature (m.p. 54-57°C). Yield 84.5%. The chemical shifts (d-acetone, ppm) for Ή NMR are similar to the hexafluorophosphate salt.

Example 4: l-Benzyl-3-butylimidazolium bromide [Bzbim][Br] The salt was prepared using the method described for [bmim][Br]. The reaction was highly exothermic, then 1-butylimidazole (0.11 mole, 14gr) was added slowly (without external heating) to benzylbromide (0.11 mole, 19.28gr) at such a rate as to keep the temperature below 65 °C. The product [Bzbim][Br] (checked by H NMR) was obtained as a slightly yellow viscous oil. Yield almost 100%. The 1H NMR spectrum (Bruker 200 MHz) for [Bzbim][Br] (d-acetone) consist of the following peaks: δ (ppm): 0.94 (t, (CH2)3CH3, 3H), 1.35 (sextet, (CH2)2CH2CH3, 2H), 1.88 (q, CH2CH2CH2CH3, 2H), 4.30 (t, CH2(CH2)2CH3, 2H), 5.60 (s, 1-CH2, 2H), 7.40 (m, H 4,5 and phenyl-H, 7H), 10.56 (s, H 2, 1H).

Example 5: l-Benzyl-3-butylimidazolium hexafluorophosphate [Bzbim][PF6] [Bzbim][Br] (0.046 mole, 13.4382gr) was transferred to a 0.5 L plastic container followed by the addition of 180 ml of deionized water. An aqueous solution of 60-65% HPFe in a 1.2: 1 molar ratio was added at such a rate as to keep the temperature below 65°C. Addition of HPF6 formed two phases, where [Bzim][PF6] forms the lower phase while aqueous HBr forms the upper phase. After stirring the mixture for two hours, the upper phase was decanted and 180 ml of an aqueous solution of 1.5% NaHCO3 was added followed by vigorous mixing. After the mixture settles, the upper basic phase was decanted and the lower phase was washed again with 180 ml of deionized water. After decantation of the aqueous phase the wet ionic liquid was dried by Dean stark distillation with toluene to yield the hexafluorophosphate salt as a pale yellow oily liquid. Alternatively the salt can be extracted from the water by 3 portions of 50 ml of chlroform (or dichloromethane) followed by drying with CaCl2 and evaporation of the solvent under vacuum. The chemical shifts (d-chloroform) forΉ NMR appears as follows: δ (ppm): 0.97 (t, (CH2)3CH3, 3H), 1.36 (sextet, (CH2)2CH2CH3, 2H), 1.89 (q, CH2CH2CH2CH3, 2H), 4.20 (t, CH2(CH2)2CH3, 2H), 5.36 (s, 1-CH2, 2H), 7.38 (m, H 4,5 and phenyl-H, 7H), 8.88 (s, H 2, 1H). IR (liquid film): v/cm"1 3160, 3114 (s, aromatic C-H stretch), 2965 (m, aliphatic C-H stretch), 1565, 1457 (s, sym. ring stretch).

Example 6: l-Benzyl-3-butylimidazolium tetrafluoroborate Pzbim][BF4] [Bzmim][Br] (0.057 mole, 16.94gr) was transferred to a 0.5 L plastic container followed by the addition of 180 ml of deionized water. Three portions of NaBF4 salt in a 1.2:1 total molar ratio was added . The tetrafluoroborate salt immediately separated from the aqueous phase. After stirring the mixture for two hours, it was extracted by 3 portions of 50 ml of dichloromethane(pH =6 in the water phase) . The organic layer was collected, dried over CaCl2, filtered and the solvent removed in vacuo to yield the tetrafluoroborate salt as a pale orange crystalline oily liquid. Yield 80%. Analysis of [bmim][BF4] included Ή NMR (Bruker 200 MHz). The chemical shifts (d-chlroform, ppm) for 1H NMR are identical to the hexafluorophosphate salt.

Example 7: 1,3-Dibenzylimidazolium bromide [Bz2im][Br] Benzyl bromide (0.0316 mole, 5gr) was added drop wise to a round-bottomed flask fitted with a reflux condenser under a continuous flow of nitrogen, containing a solution of 1-benzylimidazole (0.0316 mole, 5.4gr) in toluene (0.05 gr/ml). The reaction flask was heated for 24 Hr at 60-65°C with magnetic stirring until all the starting material reacted. The oily product separate from the toluene upper phase containing the unreacted starting materials. The solvent was decanted off and the residue was removed in vacuo to yield a brown solid. Yield 76%. The Ή NMR spectrum (Bruker 200 MHz) for [Bz2im][Br] (d-chloroform, ppm) consist of the following peaks: δ (ppm): 5.53 (s, 1,3-CH2, 4H), 7.34 (m, H 4,5 and phenyl-H, 12H), 10.7 (s, H 2, 1H).

Example 8: 1,3-Dibenzylimidazolium hexafluorophosphate [Bz2im][PF6] [Bz2im][Br] (0.0316 mole, 10.4gr) was transferred to a 0.5 L plastic container followed by the addition of 130 ml of deionized water. An aqueous solution of 60-65% HPF6 in a 1.2:1 molar ratio was added at such a rate as to keep the temperature below 65°C. The product precipitated as a waxy solid and was collected by filtration after mixing for two hours. The solid obtained was washed by 50 ml of 1.5% NaHCO3 solution and two portions of 50 ml deionized water until the pH of the filtrate was 7. The wet [Bz2im][PF6] was dried at 110°C on a vacuum oven for 24 Hr. The product was obtained as a white powder (m.p = 125-129°C). The Ή NMR spectrum (Bruker 200 MHz)for [Bz2im][PF6] (d-acetone) consist of the following peaks: δ (ppm): 5.58 (s, 1,3-CH2, 4H), 7.45 (m, phenyl-H, 10H), 7.77 (d, H 4,5, 2H), 9.32 (s, H 2, 1H).

Example 9: Reduction of vanillin in [BzmimJPFe] Vanillin (4-hydroxy-3-methoxy benzaldehyde) (0.38 g., 0.0025 mole) was added to a flask containing [Bzmim][PF6] (2 ml). To the resulting homogeneous solution, NaBFLt (0.3 g, 0.0079 mole) was added. The reaction mixture was stirred at room temperature for 24 hours. The reaction was quenched with water and the product (4-hydroxy-3-methoxybenzylalcohol) was extracted from the reaction mixture by diethyl ether. The ionic liquid could be separated from the quenched reaction mixture and used in the next reaction. Ή NMR: 3.86(s, -OCH3, 3H), 4.54 (s, -CH2OH5 2H).

In Table I below are given melting points and viscosity values of several compounds of formula (I).

Table I. Charactization of benzyl alkyl (aryl)imidazolium bromides The salts mentioned in Table I having Br' as the anionic moiety were exchanged with hexafluorophosphate or tetrafluoroborate anion. Table II summarizes different [BzirnAlkyl][PF6] salts that were prepared their melting points and viscosity.

Table II. Some characteristics of Benzyl-alkyl (aryl)imidazolium hexafluorophosphate/ tetrafluoroborate salts

Claims (13)

- 13 - 149339/2 CLAIMS:

1. A compound of formula (I) wherein R is a linear or branched C3-C10-alkyl, phenyl, benzyl which may optionally be substituted by alkyl or halogen, R1 is hydrogen, halogen, Ci.6-alkyl group, alkyloxy group, R2 is hydrogen, R3 is hydrogen or Ci_4-alkyl; X is halogen, AICI4-, BF4", PF6-, [(CF3SO2)2N]\ PO4"3, HPO4-2.

2. A compound according to claim 1, wherein R is a linear or branched Ci.6-alkyl or benzyl optionally substituted by halogen, R1 is hydrogen, R2 is hydrogen, R3 is H or Ci.2-alkyl5 and X is Br", BF4" or PF6\

3. A compound according to claim 1, wherein R is a linear or branched Ci.6-alkyl or benzyl substituted by halogen, R1, R2 and R3 are H, and X is Br", BF4" or PF6".

4. A compound of formula (I) according to claim 1 for use as an ionic liquid. ^

5. A compound of formula (I) according to claim 1 for use in chemical synthesis, or electrochemistry.

6. A compound of formula (I) according to claim 1 for use according to claim 1/ 5. wherein said chemical synthesis is halogenations, hydrogenations, hydroformylation, alkoxycarbonylation, polymerizations and dimerizations.

7. A compound of formula (I) according to claim 1 for use according to claim 5, wherein said chemical synthesis is reduction of carbonyls in the presence of NaBH .

8. A process for the preparation of a compound of formula (I) comprising reacting a compound of formula (II) with a compound of formula (III): 14 - 149339/2 reacting a compound of formula (IV) with a compound of formula (v):

9. (IV) (V) (I) wherein R, Rls R2, R3 and X are as defined above.

10. A process according to claim 9 wherein the compound of formula (IV) is initially melted and the compound of formula (V) is added to the melt.

11. A compound (I) as defined in any one of claims 1 to 7 for use as an ionic liquid.

12. A compound (I) as defined in any one of claims 1 to 7 for use as reaction medium in chemical synthesis or catalysis.

13. The use as defined in claim 12, said chemical synthesis or catalysis selected from halogenations, hydrogenations, reductions, hydroformylation, alkoxycarbonylation, polymerizations and dimerizations For the Applicant, REINHOLD COHN AND PARTNERS