Ionic Liquids as Green Solvents - ACS Publications - American

Chapter 2

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Ionic Liquids: Improved Syntheses and New Products Adrian J. Carmichael, Maggel Deetlefs, Martyn J. Earle, Ute Fröhlich, and Kenneth R. Seddon The QUILL Centre, The Queen's University of Belfast, Stranmillis Road, Belfast BT9 5AG, United Kingdom

We report here the improved syntheses of 1-alkyl-3methylimidazolium ionic liquids. Microwave irradiation drastically reduces the preparation time of 1-alkyl-3methylimidazolium and N-alkylpyridinium halide salts and, in addition, three halide-free routes to ionic liquids have been developed. New, chiral, imidazolium-based ionic liquids were prepared using both conventional and halide-free procedures. Chirality was introduced in the new compounds at either the cation or the anion, or both.

Introduction At present, the use of ionic liquids as solvents and/or catalysts for chemical reactions is well past infancy, with many excellent review articles available summarising their preparation, use, and advantages compared to traditional solvents (1,2,3,4,5,6,7). While much research emphasis is still placed on the syntheses of new ionic liquids, systematic physico-chemical property studies of these neoteric solvents are rare (8). Both these topics are vital in gaining a better understanding of the factors governing chemistry in an ionic liquid environment, but the impact of purity on the latter remains a neglected issue. This can be illustrated by the various melting points reported for 1-ethyl-3-

14

© 2003 American Chemical Society In Ionic Liquids as Green Solvents; Rogers, R., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2003.

15 methylimidazolium tetrafluoroborate, [C mim][BF ]; 15 °C (9), 5.8 °C (76/), 12.0-12.5 °C (//), 11 °C (12) and 14.6 °C (13). Further examples of the effects of contaminants in ionic liquids are the varying reaction efficiencies and/or specificities reported for reactions in the same ionic liquid (3,6,7). If ionic liquid purity issues are not addressed, the reasons for "ionic liquid effects" will continue as a barrier for the predictive preparation of ionic liquids for particular applications. One might ask whether the increased cost of stringently purified ionic liquids is justified. In some instances the answer may be negative if no clear advantages are presented by using an uncontaminated ionic liquid. However, by disregarding the impact of impurities on reaction rates, physico-chemical properties and toxicological data, the reliability and reproducibility of reported results becomes problematic. Furthermore, when imidazolium ionic liquids reach fruition and find industrial application, their involatile nature and recyclability advantages will certainly outweigh their price tag. In our view, an ionic liquid should first be prepared in its purest form and used as such. Thereafter water, or chloride, or both, can be added to determine the impact, if any, on the reaction being studied. If no significant reactivity differences are found, the use of a "dirty" ionic liquid could then be justified and at the same time, the production of incorrect literature data avoided.


2

4

General Syntheses of Ionic Liquids +

The general preparation of l-alkyl-3-methylimidazolium, [C„mim] ionic liquids (Figure 1) involves a consecutive quaternisation-metathetic/acid-base procedure. The first step affords a l-alkyl-3-methylimidazoIium halide precursor, [C„mim]X (/) and has two disadvantages: (a) it is time consuming; and (b) an excess of haloalkane (10-100 %) is required to achieve good yields. The latter renders the quaternisation reaction dirty, especially when long chained derivatives are prepared, since high boiling haloalkanes are difficult to remove from the reaction mixture. Together, both (a) and (b) make the first step in ionic liquid preparation cost and atom inefficient. Our efforts to clean and speed-up the initial stage of ionic liquid synthesis using microwave (mw) radiation are presented here. Although the focus of this paper is on imidazolium-based ionic liquids, the same synthetic strategies apply to pyridinium-based ionic liquids. The second step of ionic liquid preparation proceeds via metathesis with a metal salt or an acid-base neutralisation reaction, respectively, producing a stoicheiometric amount of waste M X or HX (Figure 1). Due to the excellent solvating properties of ionic liquids, these by-products become trapped and contaminate the ionic liquid. A previous study in our group has shown that another source of halide contamination is the incomplete conversion of the

In Ionic Liquids as Green Solvents; Rogers, R., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2003.

16


[C„mim]X precursor to the target ionic liquid (14). This study also detailed various procedures to minimise and analyse the halide content of hydrophobic and hydrophilic ionic liquids. Although the preparation of ionic liquids derived from halide-containing starting materials is still the most widely used, the elimination of halide contamination during synthesis is attractive. This approach was first employed by Bonhôte et al (15) and we have also developed three such alternative strategies, which are described here, using respectively fluorinated esters, alkyl sulfonates and free carbenes.

N

^ - M e ROC \=J N

R-N^N-Mel

Acid-Base

Metathesis + MY

+ HY

M = Group 1 metal or Ag Y = anion other than X

-MX R

R = Alkyl X = C1, Br or I

-N-^N'

M e

-HX R ^

l

N

- M e |

PURIFICATION

Water soluble

Water insoluble

Figure L General preparation of l-alkyl~3-methylimidazolium ionic liquids.

The preparation of ionic liquid halide precursors is not limited to the use of 1-methylimidazole or pyridine. Various acyclic and heterocyclic salts derived from the chiral pool (16) are also available for this purpose and include natural α-hydroxy acids, alkaloids and terpenes. Alternatively, chiral heterocycles can be prepared and employed as ionic liquid substrates. Chiral ionic liquids have the potential to introduce chirality and this can be achieved by using either a chiral cation or anion, or both. Surprisingly, relatively few examples of chiral ionic liquids have been published thus far (Figure 2). Howarth et al. were the


17 first to describe the synthesis of a chiral 1,3-dialkylimidazolium cation (17) starting from imidazole and a chiral alkyl chloride and our group investigated Diels-Alder reactions in lactate ionic liquids (18). More recently, three patents (16 19,20) as well as one paper (21) detailing the syntheses of various chiral ionic liquids have been published. As for the general imidazolium-based ionic liquid preparations, the majority of chiral ionic liquid syntheses involve a consecutive quaternisationmetathetic/acid-base procedure (compare Figure 1) (22). Using this general methodology, we have recently prepared new imidazolium-based ionic liquids where chirality is introduced either at the cation or the anion.


%

CATIONS

ANIONS OH

ο

I OH

Ν

Ο

Y-J Ο

Figure 2. Some reported chiral cations and anions (17,18,21).

Preparation of Ionic Liquids using Microwave Irradiation The use of microwave ovens as tools for synthetic chemistry is one of the fastest growing areas of research (23, 24). Since the first reports of microwaveassisted synthesis in 1986 (25,26) the technique has been accepted as a method for drastically reducing reaction times and for increasing yields of products compared to conventional methods (27). A key advantage of modern scientific microwave equipment is the ability to control reaction conditions very specifically, monitoring temperature, pressure, and reaction times (28). In order to take advantage of microwave heating effects, a covalent, non-conducting reaction medium or reactant needs to have a



18 high dielectric constant. In contrast, ionic liquids are ideal candidates for the exploitation of microwave heating due to their conducting, ionic nature. When an irradiated sample is an electrical conductor, the ions move through the material under the influence of an electric field, which results in a polarisation and these induced currents cause heating due to electrical resistance. Our interest in utilising microwave radiation is diverse, but the preparation of ionic liquid halide salts using multimode microwave radiation was selected as a preliminary study. This is the first time ionic liquids have been prepared using controlled microwave radiation on a large scale. Although previous reports have shown that multimode microwave ovens can be used to prepare imidazolium halide (29,50), tetrafluoroborate (31) and aluminate (32) salts (Figure 3), realistic power control cannot be achieved with a domestic microwave oven. Although the rate of heating with a domestic microwave can be moderated either by using heat dissipaters (33), or by increasing reactant volumes, these methods are undesirable since they respectively provide no power control, which can lead to product charring, and produce large amounts of unwanted solvent vapour. Therefore, due to power control restrictions associated with the use of domestic microwave ovens, most previous ionic liquid preparations could only be performed on a small scale (3 - 150 mmol) in open vessels, which necessitates an excess of haloalkane of up to 100 %, due to evaporative loss.

2X

C4H9

R —

X = BrorI 2(X-R-X) N

mw < ^ - M e R-X w — ' mw N

mw AICI3.6HP

[NH ][BF ] 4

X = Cl,Br, I

"[Aicy-

R

-N^N'

M

e

|

[BFJ-

+

Figure 3. Previous [Rmim] syntheses using domestic mw heating (29,31,32).


4

19 It should be noted that the reported preparation of tetrachloroaluminate compounds (32) must be incorrect, as employing A1C1 -6H 0 would result in irreversible formation of hydroxoaluminate species via hydrolysis of the anion. Our attempts to clean-up and speed-up the synthesis of ionic liquids included the preparation of a series of both [Rmim]X and [Rpy]X salts using controlled, multimode microwave radiation (Figure 4) in sealed vessels, as well as scaling up these reactions in an open vessel. Imidazolium and pyridinium halide salts were prepared in duplicate by adding 1.1 equivalents of a haloalkane (110 mmol) to either 1-methylimidazole or pyridine (100 mmol) in a sealed quartz reaction vessel fitted with a temperature and pressure probe (Figure 4). The former regulates the selected temperature by adjusting the microwave power input and the latter monitors the autogenous pressure. The optimum reaction conditions determined for the medium-scale, sealed vessel syntheses of [Rmim]X and [Rpy]X salts are shown respectively in Tables I and II. The most effective reaction temperature was established to be the approximate average boiling point of the employed haloalkane and the heterocycle.


3

2

Figure 4. [RmimJX (or [C mim]X) and [RpyJX (or[C„py]X) preparations using controlled mw heating. n

Due to evaporative loss, the preparation of imidazolium and pyridinium halides in open vessels often requires a large excess of the haloalkane to obtain good yields. For example, a 100% excess of 1-chlorobutane or 2-bromobutane was used by Varma et al. (29) to respectively prepare [C mim]Cl (76 % yield) and [C mim]Br (61 % yield). In contrast, all the sealed vessel preparations in 4

4


20 the current study required less than 10 % excess of the appropriate haloalkane to obtain > 95 % conversions (based on NMR) and > 87 % work-up yields, making this synthetic route more cost and reagent efficient, and hence greener. The rate at which the quaternisation of 1-methylimidazole or pyridine proceeds follows the conventional order; R-I > R-Br > R-Cl. Using microwave, as opposed to conductive heating, this reactivity order remains the same but reaction times are significantly decreased. For example, compared to conductive heating, microwave radiation accelerates the formation of [C mim]Cl, [C mim]Cl and [C mim]Cl by a factor of ca. 70 and [C| mim]Cl is generated ca. 110 times faster. [Qmim] and [C„py] bromide and iodide salts show a similar trend. 4


6

8

0

Table I. Preparation of [Rmim]X Salts on a Medium Scale: 150 - 300 mmol. [RmimJCl Power/ W Temperature/°C Microwave irradiation time / min. Conventional heating time/ min. Conversion / % Work-up yield / % [RmimJBr Power/ W Temperature °C Microwave irradiation time / min. Conventional heating time/ min. Conversion / % Work-up yield / % [RmimJI Power/W Temperature °C Microwave irradiation time / min. Conventional heating time/ min. Conversion / % Yield/%

R —C^g 300 150 20

R = Cfi/Z/i 300 150 20

R = CsHiy 300 180 20

1440

1440

1440

1080

>95 95 240 80 6

>95 95 R = CJln 240 80 8

>95 90 R = QH 240 110 8

>95 95 R = CioH 240 120 10

840

960

960

1080

>95 87 R ^C^Hg 200 165 4

>95 91 R = CtjHu 200 190 7

>95 >95 95 95 R = CsH/7 R = 200 200 165 210 11 9

640

720

720

720

>95 93

>95 90

>95 95

>95 94

R ~C4Hg

/7

R -

C10H21

300 120 10

21


C0H21

21


A further result of haloalkane reactivity differences is that the chloride preparations require higher power levels (300 W) than the bromides (240 W), which in turn require greater levels than the iodides (200 W) to achieve similar yields. In addition, shorter irradiation times are required for bromide and iodide preparations than for the chlorides. It is of interest to note that despite the high temperatures employed during synthesis, no imidazolium-based disproportionation products were observed.

Table II. Preparation of [Rpy]X Salts on a Medium Scale: 150 - 300 mmol. [RpyJCl Power/ W Temperature/°C Microwave irradiation time /min. Conventional heating time/ min. Conversion / % Work-up yield / % [RpyJBr Power/ W Temperature/°C Microwave irradiation time /min. Conventional heating time/ min. Conversion / % Work-up yield / % [RpyJI Power/ W Temperature/°C Microwave irradiation time / min. Conventional heating time/ min. Conversion / % Work-up yield / %

300 120 40

300 120 60

R = CsH| 300 150 60

3360

3360

3360

2880

>95 87

>95 94 R = CgHn 240 130 30

>95 93

240 130 30

>95 94 R = CeHis 240 130 30

240 130 20

2880

2880

2880

2880

>95 98

>95 98 R = CgHn 200 210 15

>95 93

10

>95 100 R = CeH 200 190 12

960

960

1080

1140

>95 95

>95 97

>95 97

>95 93

—C4HQ

R

R

=

R

C4Hg

~C4HQ

200 165

R = C Hi3 6

13

7

R = Cuflu 300 180 60

R = C10H21

R -

C10H21

200 165 15



22 For the large scale [Rmim]X and [Rpy]X salt preparations (300 mmol-2 mol) a conventional reflux arrangement was employed. A one-litre roundbottomed flask equipped with a temperature probe housing was placed inside the microwave reactor cavity, with a reflux condenser protruding through an aperture in the reactor roof. All reactions were performed at the boiling point of the appropriate haloalkane and gave conversions > 95 and yields > 85 %. On these scales, the reaction times were between 200 - 400 times shorter compared to conductive heating. Both the sealed and open vessel reactions were optimised by determining the time required for complete conversion of 1-methylimidazole to product and purity subsequently ensured washing with either ethyl ethanoate or hexane. To summarise, using microwave radiation, the first step in the general synthesis of ionic liquids has been transformed from a time-consuming, dirty process to a rapid, more environmentally-friendly procedure. This was achieved in two ways: (a) using 100 cm sealed reaction vessels; or (b) a one-litre reflux set-up. Although the latter is a less laborious method, the former allows up to fourteen sealed vessels to be used simultaneously in a parallel approach. 3

Preparation of Halide-free Ionic Liquids During the second step of the general syntheses of ionic liquids (see Figure 1) the intrinsically good solvating properties of ionic liquids become a problem. Both the metathetic and acid-base neutralisation reactions generate a stoicheiometric amount of halide waste. Many ionic liquids solvate the generated halide waste so effectively that complete removal can often not be achieved. When metathesis is carried out using a silver(I) salt, the route gives purer ionic liquid products but becomes prohibitively expensive upon scale up and residual silver must be removed electrochemically (34). Employing alkali metal salts reduces the cost, but not the waste. Halide contamination of ionic liquids is a problem that must be overcome for them to be used as reaction solvents on a large scale. For instance, when used as media for many processes catalysed by transition metals the presence of strongly coordinating halide ions has been shown to reduce catalyst activity (35,36,37,38). The opportunity also exists in many reactions for the residual halides to be oxidised to halogens, which will react with many substrates and can corrode equipment. We have recently developed three synthetic strategies that eliminate halide contamination during ionic liquid synthesis and consequently reduce the amount of waste products. The first two methods are based on the use of fluorinated esters and alkyl sulfonates (39) as replacements for haloalkanes while the third makes use of free carbenes (40). All three methods are discussed.


23 Halide-free Ionic Liquids from Fluorinated Esters and Alkyl Sulfonates Using an analogous procedure to Bonhôte's (75) original method, trifluoroethanoate, [CF C0 ]\ or methanesulfonate, [CH3SO3]*, ionic liquids were respectively obtained in excellent yields by heating equimolar amounts of 1-methylimidazole and either a fluorinated ester or an alkyl sulfonate, under reflux, (Figure 5). The quaternisation reactions are time-consuming but this could be overcome using microwave radiation in a solvent-free procedure. The [C mim]Y (n = 4 or 6; Y = [CF C0 ]) ionic liquids are available as room temperature reaction media, but the [C mim] analogues melt above ambient temperature and can therefore not be employed as room-temperature solvents. Nevertheless, these methods provide two new routes to novel, halide-free ionic liquids. If ionic liquids with anions other than [CF C0 ]" or [CH3SO3]" are desired, the former can be used as metathetic substrates to produce e.g. hexafluorophosphate or tetrafluoroborate halide-free ionic liquids (Figure 5). The reactions respectively release trifluoroethanoic (CF COOH) and methanesulfonic (CH S0 H) acid as by-products (Figure 5). Trifluoroethanoic acid is too expensive a commodity to be produced as waste, but fortunately its low boiling point of 72 °C makes it recyclable (Figure 6). Recycling is simple 3

2

n

3

2


2

3

2

3

3

3

Figure 5. [Rmim][CF C0 ] and [Rmim][CH S0 ] preparations (39). 3

2

3

3


24 H0 2


[Rmim]X

mim Figure 6. Recycling of trifluoroethanoic acid (39).

and involves distilling trifluoroethanoic acid out of the non-volatile ionic liquid at 100 °C and at atmospheric pressure. Trifluoroethanoic acid is easily collected by distillation and reintroduced into the reaction cycle either by direct esterification of the acid, or by dehydration via the anhydride (Figure 6). In this way, the costly recyclable reagent is reused in a sustainable cycle. Methanesulfonic acid can similarly be recycled although its high boiling point of ca. 150 °C makes its separation from the product ionic liquid more difficult. It should also be noted that due to the low pH of methanesulfonic acid, it can only normally be exchanged using an acid with a higher pH. However, this potential problem can be overcome by anion exchange with Group 1 metal salts of the desired anion in water, followed by extraction with a water immiscible solvent such as ethyl ethanoate or dichloromethane. This method bypasses the anion exchange problem since [Rmim][CH S0 ] and methanesulfonic acid are hydrophilic while [Rmimjfanion] almost always dissolves in organic solvents. Exceptions of course exist for hydrophilic anions such as sulphate or phosphate. In addition, if the desired ionic liquid is hydrophobic, it will separate from the water layer making its isolation simple. 3


3

25

Halide-free Ionic Liquids from Imidazolium-based Carbenes The third method we have recently developed to prepare halide-free ionic liquids exploits the acidity of H-2 in [Rmim]X salts (40). These salts are easily deprotonated with a strong base such as K[OCMe ] to afford the corresponding free carbene (Figure 7). These reactions have been extensively studied since Arduengo isolated the first stable free carbene in 1991 (41) and a variety of procedures to synthesise free heterocyclic (diamino)carbenes are currently available (42,43,.44) Our initial work was based on these methods and involved the use of alkyllithium bases such as butyllithium or lithium diisopropylamide to deprotonate [Rmim]X salts in tetrahydrofuran. Although these methods produced imidazolium-based free carbenes, product isolation was laborious and yields low. Nevertheless, due to the stability of Arduengo-type free carbenes (44) we were able to isolate a series of l-alkyl-3-methylimidazol-2-ylidenes (Figure 7) by Kugelrohr distillation in a solvent free procedure. Heating an equimolar mixture of [Rmim]X with K[OCMe ] affords free carbenes in excellent yields (Table III), which were isolated by vacuum distillation. A variety of anions was subsequently introduced by equimolar


3

3

Ο

KOCMe ] „ t

R^

N

^

3

M

-

M

2

R

CH OH 3

CH C0 H 3

[Rmim][HC0 ]

2

CH3SO3H

^N^N'

3

M e

[OH]"

w-C H OH| 3

7

[Rmim][C H 0]

[Rmim][CH C0 ]

3

Η

H,0

e

- M e | Cl"

oyH o

Η

3

2

7

fRmim][CH S0 ]

[Rmim][CH 0]

3

3

R — C H J Î C^Hgî CgH| 2

3

7

Figure 7. Imidazolium carbene routes to halide-free ionic liquids (40).


26 addition of a free carbene to the Brénsted acid form (Figure 7) of the desired anion. In addition to providing a straightforward route to prepare a wide range of halide-free ionic liquids, this is the only known method to prepare unstable [Rmim][OH] salts as well as [Rmim][HC0 ] and [Rmim][OR] ionic liquids. The hydroxide was isolated as the hydrated salt and characterised by NMR spectroscopy. Complete dehydration of the salt was not possible. The hydroxide (a viscous oil) is unstable and slowly disproportionates at room temperature as illustrated in Figure 7. The C-NMR spectra of the "propoxide ionic liquid" (C-2 signal at δ 190) suggest that it is intermediate between a solution of the carbene (6C 210 p.p.m.) and an imidazolium salt with the C-2 signal at δ 135 p.p.m. This also suggests that the p^ 's of the imidazolium salt and 1-propanol are similar. 3


13

a

Table III.

Synthesis of l-Alkyl-3-methylimidazol-2-ylidenes using K[OCMe ] 3

[RmimJCl [C mim]Cl [C mim]Cl [C mim]Cl 2

4

8

Reaction Temp. Product bp /"CatlmmHg /"C 120 90 150 120 200 180

Yield/% 95 90 70

At the time of our initial study, it was generally accepted that free imidazolinylidenes required bulky groups on the nitrogen atoms to provide the necessary steric and electronic stability to exist in free form. In our hands, free carbenes such as l-ethyl-3-methylimidazol-2-ylidene proved to be stable enough to be handled at both room temperature and elevated temperatures under dry conditions. To summarise, the utilisation of imidazolium-based free carbenes provides a simple, relatively cheap method to prepare halide-free ionic liquids without the generation of noxious waste products.

Chiral Ionic Liquids With the growing number of reactions that can be performed in ionic liquids, the possibility of chiral induction through the use of a chiral ionic liquid is intriguing. The improved synthesis of an ionic liquid, based on a chiral cation, previously reported by Herrmann et al (45), was performed as shown in Figure 8. The chiral imidazolium cation was prepared starting from the readily available chiral amine, 1-phenylethylamine, using a method based on the current


27 fi ^

Ο ΝΗ

Ο

Ph

CH C02H

+ Η Ν~

Ionic Liquids as Green Solvents - ACS Publications - American

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