# Patent

## Title
Method of preparing a high purity imidazolium salt

## Abstract

The present invention encompasses a novel method for synthesizing highly pure salts of the general formula Q+A−, wherein Q+ is:




and wherein A− is

## Background
CROSS REFERENCE TO RELATED APPLICATIONS
The present application claims priority under 35 USC §119 to European application, EP16174303.4, filed on Jun. 14, 2016, the contents of which is incorporated herein by reference in its entirety.
FIELD OF THE INVENTION
The invention relates to a method of preparing a high purity imidazolium salt.
BACKGROUND OF THE INVENTION
In air conditioning systems for the aeration and conditioning of buildings or vehicles, the air generally not only has to be cooled, but also dehumidified since the air to be cooled often has such a high humidity that, upon cooling to the desired temperature, the dew point is fallen below. Hence in conventional air conditioning systems dehumidification of the air accounts for a large part of the electricity consumption.
One option of reducing the electricity consumption of air conditioning systems for buildings is the dehumidification of air by adsorption or absorption of water using a drying medium and a regeneration of the drying medium laden with water by heating to a temperature at which the water is desorbed again. Compared to adsorption on a solid adsorbent, the advantage of absorption in a liquid absorption medium is that drying of air can be performed with reduced equipment complexity and with less drying medium and that regeneration of the water-laden drying medium using solar heat is easier to carry out.
The aqueous solutions of lithium bromide, lithium chloride or calcium chloride hitherto employed as liquid absorption media in commercial air conditioning systems have the disadvantage that they are corrosive towards the metallic materials of construction typically employed in air conditioning systems and that they thus necessitate the use of expensive specific materials of construction. These solutions can additionally cause problems due to salt crystallizing out of the absorption medium.
Ionic liquids comprising dialkylimidazolium ions (as described in WO 2004/016631 A1) have been described as alternatives to lithium salts in the prior art for similar applications. Y. Luo et al., Appl. Thermal Eng. 31 (2011) 2772-2777 proposes the ionic liquid 1-ethyl-3-methylimidazolium tetrafluoroborate in place of aqueous solutions of lithium bromide for drying of air.
Y. Luo et al., Solar Energy 86 (2012) 2718-2724 proposes the ionic liquid 1,3-dimethyimidazolium acetate as an alternative to 1-ethyl-3-methylimidazolium tetrafluoroborate for drying of air.
US 2011/0247494 A1 proposes, in paragraph [0145], the use of trimethylammonium acetate or 1-ethyl-3-methylimidazolium acetate as liquid drying agent instead of aqueous lithium chloride solution. Example 3 compares water uptake from humid air for a series of further ionic liquids.
However, a problem of ionic liquids comprising dialkylimidazolium ions is that they often comprise impurities, which lead to substances that are odour-intensive or are injurious to health entering the dehumidified air upon a dehumidification of air using the ionic liquid. Moreover, it has been found that during the desorption of water from ionic liquids which contain a basic anion, such as, for example, a carboxylate ion, odour-intensive decomposition products are formed which, in the event of a subsequent use of the ionic liquid for the dehumidification of air, enter the dehumidified air.
Therefore, there remains a need for ionic liquids comprising imidazolium ions, which do not display the disadvantages described above. The problem to be solved by the present invention is hence provision of a process for the production of ionic liquids comprising dialkylimidazolium ions, wherein the level of volatile compounds is brought to a minimum.


DETAILED DESCRIPTION OF THE INVENTION
It has been surprisingly found that the above problem is solved by the process described hereinafter.
The invention hence provides a process for preparing a high purity compound of formula (I):

Q+A−,

wherein Q+ is





and wherein A− is





the process comprising:

    
    
        a) reacting a compound of formula (II) with a compound of formula (III), wherein (II) and (III) are:
    
    






    
    
        
        
            to give a crude product comprising a compound of formula (I);
        
        
        b) adding water to the crude product of formula (I) from step a), to give a diluted crude product comprising a compound of formula (I);
        c) at least partial removal of the water added in step b) from the diluted crude product by distillation of the diluted crude product at a temperature T1 in the range of 30-180° C. and at a pressure p1 which is lower than the saturated vapour pressure of compound (III) at the temperature T1, giving a high purity compound of formula (I);

wherein:

each of R1, R2, R3 are independently a hydrogen or alkyl of 1 to 4 carbon atoms,

each of R4, R5, R6, R7 are independently alkyl of 1 to 4 carbon atoms.

    
    


In a preferred embodiment of the present invention, R1═R2═R3=hydrogen and each of R4, R5, R6, R7 are independently methyl or ethyl. In a more preferred embodiment of the present invention, R1═R2═R3=hydrogen, R5=methyl and each of R4, R6, R7 are independently methyl or ethyl. In an even more preferred embodiment of the present invention, R1═R2═R3=hydrogen, R5=methyl and R4═R6═R7=ethyl.
In step a) of the process according to the invention, a compound of formula (II) with a compound of formula (III) is reacted, giving a crude product comprising a compound of formula (I). The skilled person is familiar with the reaction conditions, which are described in WO 2004/016631 A1, for example.
In particular, step a) of the process according to the invention is preferably carried out at a temperature in the range of from 130° C. to 200° C., more preferably 140° C. to 190° C., even more preferably 150° C. to 175° C.
The pressure of the reaction is not critical and may be for example atmospheric pressure, preferably under an inert atmosphere, such as nitrogen.
As the reaction is exothermic, it may be desirable to control the rate of addition in some cases and/or to apply external cooling during the addition step.
In general, the compounds of formula (II) and (III) are present in stoichiometric amounts, i.e. the molar relation of compound (II) to compound (III) is in the range 0.9:1 to 1.1:1, more preferably 1:1. In some cases, it might be advantageous to use the imidazole compound (II) in a slight excess to the phosphate ester (III), for example in the range of 1.01 to 1.4 molar equivalents, preferable 1.02 to 1.4.
The reaction time is not particularly limited. Typically, the reaction is continued until at least 90% of the compounds (II) or (III) has reacted to form compound (I). The progress of the reaction can be conveniently controlled by methods known to the skilled person, such as NMR
The reaction in step a) can be carried out in the presence or absence of a solvent and is preferably carried out in the absence of a solvent.
“Solvent” means water or organic solvents which are known to the skilled person, preferably it means water. These organic solvents are preferably selected from the group consisting of aliphatic solvents, preferably pentane, hexane, heptane, octane, decane, cyclohexane, tetramethylsilane; aromatic solvents, preferably benzene, toluene, xylene; ether compounds, preferably diethyl ether, dipropyl ether, dibutyl ether, methyl tert-butyl ether; halogenated solvents, preferably dichloromethane, chloroform, tetrachloromethane; alcohols, preferably methanol, ethanol, propanol, iso-propanol, butanol, tert-butanol; esters, preferably methyl acetate, ethyl acetate, propyl acetate, butyl acetate; acetone. Especially preferred organic solvents are selected from esters, alcohols.
“Absence of a solvent” means particularly that the overall content of all solvents in the reaction mixture is below 10 weight-% based on the sum of the weights of compounds (II) and (III), preferably below 5 weight-% based on the sum of the weights of compounds (II) and (III), more preferably below 1 weight-% based on the sum of the weights of compounds (II) and (III).
“Presence of a solvent” means that the sum of all solvents present in the reaction mixture is at least 1.0 weight-%, based on the combined masses of compounds (II) and (III). Even more preferred, it means that the sum of all solvents present in the reaction mixture is at least 3.7 weight-%, based on the combined masses of compounds (II) and (III). Even more preferred, it means that the sum of all solvents present in the reaction mixture is at least 7.4 weight-%, based on the combined masses of compounds (II) and (III). Even more preferred, it means that the sum of all solvents present in the reaction mixture is at least 10.0 weight-%, based on the combined masses of compounds (II) and (III). Even more preferred, it means that the sum of all solvents present in the reaction mixture is at least 20.0 weight-%, based on the combined masses of compounds (II) and (III). Even more preferred, it means that the sum of all solvents present in the reaction mixture is at least 40.0 weight-%, based on the combined masses of compounds (II) and (III). Even more preferred, it means that the sum of all solvents present in the reaction mixture is at least 80 weight-%, based on the combined masses of compounds (II) and (III). Even more preferred, it means that the sum of all solvents present in the reaction mixture is at least 100 weight-%, based on the combined masses of compounds (II) and (III). Even more preferred, it means that the sum of all solvents present in the reaction mixture is at least 150 weight-%, based on the combined masses of compounds (II) and (III).
In the embodiment of the invention in which the step a) is carried out in the presence of a solvent, it is preferred that the solvent is at least partially removed after step a) before step b) is carried out. Such at least partial removal can be carried out by extraction, stripping, distillation or any other process known to the skilled person, preferably by extraction, stripping, distillation. In this context, “partial removal” means in particular, that at least 50% of the solvent added in step a) is removed, preferably at least 70%, even more preferably at least 90%, even more preferably 99% of the solvent is removed.
In case step a) is carried out in the presence of a solvent comprising water, the partial removal of the solvent is preferably carried out by distillation at a temperature T2 in the range of 30-180° C., preferably 37° C.-178° C., even more preferably 50° C.-150° C., even more preferably 60° C.-120° C., even more preferably 70° C.-99° C., and at a pressure p2 which is lower than the saturated vapour pressure of compound (III) at the temperature T2.
In a preferred embodiment, the pressure p2 is also higher than the saturated vapour pressure of the compound (I), even more preferably higher than the saturated vapour pressure of a mixture of compound (I):water=99:1, even more preferably 98:2, even more preferably 97:3.
The result of the reaction of step a) of the method according to the invention is a crude product comprising a compound of formula (I).
Within the context of the invention, the term “crude product” means the reaction mixture which is obtained after the reaction has taken place [step a) of the process according to the invention] and is then submitted to step b). As stated above, in case step a) is carried out in presence of a solvent, such solvent can be optionally removed at least partially from the crude product obtained after step a) before step b) is carried out.
The crude product obtained in step a) is then further processed in step b). In step b), water is added to the crude product of formula (I) from step a), preferably in an amount of at least 1 weight-% based on the amount of compounds (II) and (III) used in step a), giving a diluted crude product comprising a compound of formula (I).
Preferably, in step b) water is added to the crude product of formula (I) from step a) in an amount in the range of 1 to 200, more preferably 5 to 100, even more preferably 7 to 75, even more preferably 10 to 50, most preferably 15 to 20 weight-% based on the amount of compounds (II) and (III) used in step a).
Within the context of the invention, the term “diluted crude product” means the mixture which is obtained after the addition of water according to step b) and is then submitted to step c).
In step c) of the process, the water added in step b) is then at least partially removed from the diluted crude, wherein special temperature and pressure conditions are applied. Namely, it is essential to the invention that the water is removed by distillation at a temperature T1 in the range of 30-180° C., preferably 37° C.-178° C., even more preferably 50° C.-150° C., even more preferably 60° C.-120° C., even more preferably 70° C.-99° C., and at a pressure p1 which is lower than the saturated vapour pressure of compound (III) at the temperature T1.
“At least partially removed” in the context of the invention with respect to claim c) means, that at least 50% of the water added in step b) is removed, preferably at least 70%, even more preferably at least 90%, even more preferably 99% of the water added in step b) is removed.
For carrying out the distillation, all apparatuses known to the person skilled in the art can be used, thus e.g. a stirred reactor, a falling-film evaporator or a thin-film evaporator, in each case in combination with a suitable distillation column or another apparatus suitable for the distillation.
The pressure p1 at which the distillation takes place has to be lower than the saturated vapour pressure of compound (III) at the temperature T1, wherein T1 is in the range of 30-180° C.
In a preferred embodiment, the pressure p1 is also higher than the saturated vapour pressure of the compound (I), even more preferably higher than the saturated vapour pressure of a mixture of compound (I):water=99:1, even more preferably 98:2, even more preferably 97:3.
“Saturated vapour pressure” of a certain substance or mixture is defined as the pressure exerted by a vapour of this substance or mixture in thermodynamic equilibrium with its condensed phases (solid or liquid) at a given temperature in a closed system.
The saturated vapour pressure at the respective temperature can be determined by the skilled person by methods known in the art. For example, and according to the invention, the saturated vapour pressures of a certain substance or mixture is determined as set forth in the OECD Guidelines for the Testing of Chemicals (1981): Test No. 104, items 14-19 “Static Method”, adopted Mar. 23, 2006.
In a preferred embodiment of the method according to the present invention, steps b) and c) are carried out at least twice, even more preferably at least three times, wherein step b) is carried out with the high purity compound of formula (I) obtained in directly antecedent step c).
It has now surprisingly been found that, only when the combination of the water addition step b) and the distillation step c) according to the method of the invention is carried out, the product obtained at the end of step c) has as unexpectedly low level of odour-intensive and smelly substances. This is even more surprising as a skilled person would not have treated the crude product (I) obtained after step a) with water, especially because compound (I) is in fact to be used as water-absorbing material.
The method of the present invention thus provides as a product a highly pure imidazolium salt.
The following examples illustrate the invention.
EXAMPLES
Materials
In the following examples, N-methylimidazole (CAS number: 616-47-7) and triethylphosphate (CAS number: 78-40-0) were purchased from Sigma Aldrich.
Methods
The saturated vapour pressures were determined by the method described in: OECD Guidelines for the Testing of Chemicals (1981): Test No. 104, items 14-19 “Static Method”, adopted Mar. 23, 2006.
The saturated vapour pressure determined by this method for triethylphosphate follow the formula <1> wherein

log10(p)=16.42−5108.4/(273.15+T)  <1>.

In formula <1>, p is the pressure in hPa, T is the temperature in ° C., “log10” is the common logarithm.
The saturated vapour pressure of triethylphosphate at 150° C.=22268 hPa,
at 140° C.=11363 hPa, at 120° C.=2669.9 hPa, at 99° C.=493.5, at 85° C.=143.5 hPa, at 70° C.=34.1 hPa, at 60° C.=12.2 hPa, at 50° C.=4.1 hPa.
The saturated vapour pressure of a mixture of 99 parts of 1-ethyl-3-methylimidazolium diethylphosphate (=EMIM DEP) and 1 part of water are as follows: at 150° C.=380 hPa, at 140° C.=254 hPa, at 85° C.=18.6 hPa, at 60° C.=4.2 hPa.
The residuals in each sample were determined by olfactory analysis.
In addition, the residuals in samples obtained in V1-V4 and E1-E3 were determined by headspace GC/MS as follows: 0.1 g of the sample was incubated for 20 minutes at 70° C. in a sampler. The composition of the gas phase was analyzed directly with gas chromatography (“GC”) and mass spectrometry (“MS”). GC is performed with an apparatus of Hewlett Packard (“HP 6890”; sampler: Turbomatrix 40, Perkin Elmer). MS is performed with an apparatus of Hewlett-Packard (“HP 5973”).
The quantity of the residuals are determined based on the peak height observed in the chromatogram.
General Procedure for Inventive Examples E1-E8 and Comparative Examples V1-V8
Triethylphosphate (929 g, 5.0 mole) was added dropwise to a reaction vessel containing N-methylimidazole (411 g, 5.0 mole). Afterwards the reaction mixture was heated up to 150° C. and stirred under reflux for 14 h. Then, the mixture was diluted with 20 weight-% of water (based on the sum of the masses of the starting materials triethylphosphate and N-methylimidazole) and the water was distilled of at different pressures as summarized in the following table.
In comparative example V1, the treatment with water was omitted and the mixture merely moved to a rotary evaporator.
In all examples except V1, 93.8 g water (=7 weight-% based on the combined masses of triethylphosphate and N-methylimidazole used in the general procedure) were added. In examples V2-V4, the water was removed at 60° C. and a pressure of 20 hPa, which is above the saturated vapour pressure of triethylphosphate at the respective temperature (12.2 hPa).
In example V5, the water was removed at 50° C. and a pressure of 5 hPa, which is above the saturated vapour pressure of triethylphosphate at the respective temperature (4.1 hPa).
In example V6, the water was removed at 60° C. and a pressure of 14 hPa, which is above the saturated vapour pressure of triethylphosphate at the respective temperature (12.2 hPa).
In example V7, the water was removed at 70° C. and a pressure of 37 hPa, which is above the saturated vapour pressure of triethylphosphate at the respective temperature (34.14 hPa).
In example V8, the water was removed at 99° C. and a pressure of 540 hPa, which is above the saturated vapour pressure of triethylphosphate at the respective temperature (493.5 hPa).
In inventive examples E1-E3, water was added, and the water was removed at 60° C. (E1, E2) or 85° C. (E3) and a pressure of 5 and 20 hPa, respectively, which is below the saturated vapour pressure of triethylphosphate at the respective temperatures (12.2 hPa at 60° C. and 143.5 hPa at 85° C.).
In example E4, the water was removed at 50° C. and a pressure of 3 hPa, which is below the saturated vapour pressure of triethylphosphate at the respective temperature (4.1 hPa).
In example E5, the water was removed at 60° C. and a pressure of 10 hPa, which is below the saturated vapour pressure of triethylphosphate at the respective temperature (12.2 hPa).
In example E6, the water was removed at 70° C. and a pressure of 31 hPa, which is below the saturated vapour pressure of triethylphosphate at the respective temperature (34.1 hPa).
In example E7, the water was removed at 99° C. and a pressure of 440 hPa, which is below the saturated vapour pressure of triethylphosphate at the respective temperature (493.5 hPa).
In example E8, the water was removed at 120° C. and a pressure of 1000 hPa, which is below the saturated vapour pressure of triethylphosphate at the respective temperature (2669.9 hPa).

















Distillation
Repetitions 






at T
of adding 





Water
[°C.]/p
water und
Residual



Example
added?
[hPa]
distillation
[ng/g]
odor







V1
No
150/50 
0
3049
sweet and 







slightly fishy


V2
Yes
60/20
1
1021
slightly fishy


V3
Yes
60/20
2
 407
slightly fishy


V4
Yes
60/20
3
 297
very slightly







fishy


V5
Yes
50/5 
1

slight sweet


V6
Yes
60/14
1

slight sweet


V7
Yes
70/37
1

slight sweet


V8
Yes
 99/540
1

slight sweet


E1
Yes
60/5 
1
 70
No smell


E2
Yes
60/5 
3
n.d.* (<10)
No smell


E3
Yes
85/20
3
n.d.* (<10)
No smell


E4
Yes
50/3 
1

No smell


E5
Yes
60/10
1

No smell


E6
Yes
70/31
1

No smell


E7
Yes
 99/440
1

No smell


E8
Yes
 120/1000
1

No smell





* “n.d.” = “not detectable” 






The above summarized result show that only when the combination of the water addition step b) and the removal step c), only when carried out under the distillation conditions according to the invention, lead to the highly pure imidazolium salt.
All references cited herein are fully incorporated by reference. Having now fully described the invention, it will be understood by those of skill in the art that the invention may be practiced within a wide and equivalent range of conditions, parameters and the like, without affecting the spirit or scope of the invention

## Claims

1. A process for preparing a high purity compound of formula (I): Q+A−,
wherein Q+ is:




and wherein A− is:




the process comprising:
a) reacting a compound of formula (II) with a compound of formula (III), wherein (II) and (III) are:





to give a crude product comprising a compound of formula (I);

b) adding water to the crude product of formula (I) from step a), to give a diluted crude product comprising a compound of formula (I);
c) at least partial removal of the water added in step b) from the diluted crude product by distillation of the diluted crude product at a temperature T1 in the range of 30-180° C. and at a pressure p1 which is lower than the saturated vapour pressure of compound (III) at the temperature T1, giving a high purity compound of formula (I);
wherein:
each of R1, R2, R3 are independently a hydrogen or alkyl of 1 to 4 carbon atoms;
each of R4, R5, R6, R7 are independently alkyl of 1 to 4 carbon atoms.

2. The process of claim 1, wherein R1═R2═R3=hydrogen and wherein each of R4, R5, R6, R7 are independently methyl or ethyl.

3. The process of claim 2, wherein R1═R2═R3=hydrogen, R5=methyl and wherein each of R4, R6, R7 are independently methyl or ethyl.

4. The process of claim 1, wherein step a) is carried out in the absence of a solvent.

5. The process of claim 1, wherein step a) is carried out in the presence of a solvent.

6. The process of claim 5, wherein the solvent is at least partially removed between steps a) and b).

7. The process of claim 1, wherein, in step b), water is added in an amount of at least 1 weight-% based on the amount of compounds (II) and (III) used in step a).

8. The process of claim 1, wherein “partial removal” in step c) means removal of at least 50% of the water added in step b).

9. The process of claim 1, wherein pressure p1 is lower than the saturated vapour pressure of compound (III) at the temperature T1 and higher than the saturated vapour pressure of (I) at the temperature T1.

10. The process of claim 1, wherein steps b) and c) are carried out at least twice, and wherein step b) is carried out with the high purity compound of formula (I) obtained in directly antecedent step c).

11. The process of claim 2, wherein said process is carried out in the absence of an organic solvent.

12. The process of claim 11, wherein in step b) water is added in an amount of at least 1 weight-% based on the amount of compounds (II) and (III) used in step a).

13. The process of claim 12, wherein “partial removal” in step c) means removal of at least 50% of the water added in step b).

14. The process of claim 13, wherein pressure p1 is lower than the saturated vapour pressure of compound (III) at the temperature T1 and higher than the saturated vapour pressure of (I) at the temperature T1.

15. The process of claim 14, wherein steps b) and c) are carried out at least twice, and wherein step b) is carried out with the high purity compound of formula (I) obtained in directly antecedent step c).

16. The process of claim 3, wherein said process is carried out in the absence of an organic solvent.

17. The process of claim 16, wherein in step b) water is added in an amount of at least 1 weight-% based on the amount of compounds (II) and (III) used in step a).

18. The process of claim 17, wherein “partial removal” in step c) means removal of at least 50% of the water added in step b).

19. The process of claim 18, wherein pressure p1 is lower than the saturated vapour pressure of compound (III) at the temperature T1 and higher than the saturated vapour pressure of (I) at the temperature T1.

20. The process of claim 19, wherein steps b) and c) are carried out at least twice, and wherein step b) is carried out with the high purity compound of formula (I) obtained in directly antecedent step c).