Wasserscheid P., Welton T. - Ionic Liquids in Synthesis (2002)(en)

276 Hélène Olivier-Bourbigou, Alain Forestière

and recyclable system for the production of ethylbenzene (benzene/ethene alkylation) and synthetic lubricants (alkylation of benzene with 1-decene). The production of linear alkyl benzene (LAB) has also been developed by Akzo [43].

The ethylbenzene experiments were run by BP in a pilot loop reactor similar to that described for the dimerization (Figure 5.3-8).

Ionic liquids operate in true biphasic mode. While the recovery and recyclability of ionic liquid was found to be more efficient than with the conventional AlCl3 catalyst (red oil), the selectivity for the monoalkylated aromatic hydrocarbon was lower. In this gas-liquid-liquid reaction, the solubility of the reactants in the ionic phase (e.g. the benzene/ethene ratio in the ionic phase) and the mixing of the phases were probably critical. This is an example in which the engineering aspects are of the utmost importance.

The use of acidic chloroaluminates as alternative liquid acid catalysts for the alkylation of light olefins with isobutane, for the production of high octane number gasoline blending components, is also a challenge. This reaction has been performed in a continuous flow pilot plant operation at IFP [44] in a reactor vessel similar to that used for dimerization. The feed, a mixture of olefin and isobutane, is pumped continuously into the well stirred reactor containing the ionic liquid catalyst. In the case of ethene, which is less reactive than butene, [pyridinium]Cl/AlCl3 (1:2 molar ratio) ionic liquid proved to be the best candidate (Table 5.3-4).

The reaction can be run at room temperature and provides good quality alkylate (dimethylbutanes are the major products) over a period of three hundred hours.

Feed

Ionic liquid pump

Figure 5.3-8: Loop reactor as used in aromatic hydrocarbon alkylation experiments.

aVolume of olefin/(volume of ionic liquid.hour). bi-C6 = 2,2- and 2,3-dimethylbutanes, ci-C8 = isooctanes, TMP : trimethylpentanes, dC8+ = hydrocarbon products with more than eight carbon atoms, eLight ends = hydrocarbon products with fewer than eight carbon atoms, fRON = research octane number, MON = motor octane number

When butenes are used instead of ethene, lower temperature and fine-tuning of the acidity of the ionic liquid are required to avoid cracking reactions and heavy byproduct formation. Continuous butene alkylation has been performed for more than five hundred hours with no loss of activity and stable selectivity. A high level of mixing is essential for a high selectivity and thus for a good quality alkylate. These applications are promising, but efforts are still needed to compete with the existing effective processes based on hydrofluoric and sulfuric acids.

5.3.6.3Industrial use of ionic liquids

What can drive the switch from existing homogeneous processes to novel ionic liquids technology? One major point is probably a higher cost-effectiveness. This can result from improved reaction rates and selectivity, associated with more efficient catalyst recovery and better environmental compatibility.

The cost of ionic liquids can, of course, be a limiting factor in their development. However, this cost has to be weighed against that of current chemicals or catalysts.

278 Hélène Olivier-Bourbigou, Alain Forestière

If the ionic liquid can be recycled and if its lifetime is proven to be long enough, then its initial price is probably not the critical point. In Difasol technology, for example, ionic liquid cost, expressed with respect to the octene produced, is lower than that of the catalyst components.

The manufacture of ionic liquids on an industrial scale is also to be considered. Some ionic liquids have already been commercialized for electrochemical devices (such as capacitors) applications [45].

Chloroaluminate laboratory preparations proved to be easily extrapolated to large scale. These chloroaluminate salts are corrosive liquids in the presence of protons. When exposed to moisture, they produce hydrochloric acid, similarly to aluminium chloride. However, this can be avoided by the addition of some proton scavenger such as alkylaluminium derivatives. In Difasol technology, for example, carbonsteel reactors can be used with no corrosion problem.

The purity of ionic liquids is a key parameter, especially when they are used as solvents for transition metal complexes (see Section 5.2). The presence of impurities arising from their mode of preparation can change their physical and chemical properties. Even trace amounts of impurities (e.g., Lewis bases, water, chloride anion) can poison the active catalyst, due to its generally low concentration in the solvent. The control of ionic liquid quality is thus of utmost importance.

As new compounds, very limited research has been done to evaluate the biological effects of ionic liquids. The topical effect of [EMIM]Cl/AlCl3 melts and [EMIM]Cl on the integument of laboratory rat has been investigated. The study reports that [EMIM]Cl is not in itself responsible for tissue damage. However, the chloroaluminate salt can induce tissue irritation, inflammation, and necrosis, due to the presence of aluminium chloride. However, treatments for aluminium chloride and hydrochloric acid are well documented. This study needs to be expanded to the other ionic liquids, and their toxicity need to be investigated [46].

Very few data [47] relating to the disposal of used ionic liquids are available. In Difasol technology, the used ionic liquid is taken out of the production system and the reactor is refilled with fresh catalyst solution.

5.3.7

Concluding Remarks and Outlook

In comparison with classical processes involving thermal separation, biphasic techniques offer simplified process schemes and no thermal stress for the organometallic catalyst. The concept requires that the catalyst and the product phases separate rapidly, to achieve a practical approach to the recovery and recycling of the catalyst. Thanks to their tunable solubility characteristics, ionic liquids have proven to be good candidates for multiphasic techniques. They extend the applications of aqueous biphasic systems to a broader range of organic hydrophobic substrates and water-sensitive catalysts [48–50].

To be applied industrially, performances must be superior to those of existing catalytic systems (activity, regioselectivity, and recyclability). The use of ionic liquid biphasic technology for nickel-catalyzed olefin dimerization proved to be successful,

5.4 Multiphasic Catalysis with Ionic Liquids in Combination with Compressed CO2 281

5.4

Multiphasic Catalysis with Ionic Liquids in Combination with Compressed CO2

Peter Wasserscheid

5.4.1

Introduction

Ionic liquids are often viewed as promising solvents for “clean processes” and “green chemistry”, mainly due to their nonvolatile characters [1, 2]. These two catchphrases encompass current efforts to reduce drastically the amounts of side and coupling products, and also solvent and catalyst consumption in chemical processes. As another “green solvent” concept for chemical reactions, the replacement of volatile organic solvents by supercritical CO2 (scCO2) is frequently discussed [3]. scCO2 combines environmentally benign characteristics (nontoxic, nonflammable) with favorable physicochemical properties for chemical synthesis. Catalyst separation schemes based on the tunable phase behavior of scCO2 (e.g. CESS process) have been developed [4].

However, ionic liquids and scCO2 are not competing concepts for the same applications. While ionic liquids can be considered as alternatives for polar organic solvents, the use of scCO2 can cover those applications in which non-polar solvents are usually used.

With regard to homogeneous transition metal-catalyzed reactions, the two media show complementary strengths and weaknesses. While ionic liquids are known to be excellent solvents for many transition metal catalysts (see Section 5.2), the solubilities of most transition metal complexes in scCO2 are poor. Usually, special ligand designs (such as phosphine ligands with fluorous “ponytails” [3]) are required to allow sufficient catalyst concentration in the supercritical medium. However, the isolation of the product from the solvent is always very easy in the case of scCO2, while product isolation from an ionic catalyst solution can become more and more complicated depending on the solubility of the product in the ionic liquid and on the product’s boiling point.

In cases in which product solubility in the ionic liquid and the product’s boiling point are high, the extraction of the product from the ionic liquid with an additional organic solvent is frequently proposed. This approach often suffers from some catalyst losses (due to some mutual solubility) and causes additional steps in the workup. Moreover, the use of an additional, volatile extraction solvent may nullify the “green solvent” motivation to use ionic liquids as nonvolatile solvents.

Beckman, Brennecke, and their research groups were the first to realize that the combination of scCO2 and an ionic liquid can offer special advantages. They observed that, although scCO2 is surprisingly soluble in some ionic liquids, the reverse is not the case, with no detectable ionic liquid solubilization in the CO2 phase. On the basis of these results they described a method to remove naphthalene quantitatively from the ionic liquid [BMIM][PF6] by extraction with scCO2 [5]. Sub-

282 Peter Wasserscheid

sequent work by Brennecke’s team has applied the same procedure to the extraction of a large variety of different solutes from ionic liquids, without observation of any ionic liquid contamination in the isolated substances [6].

Research efforts aiming to quantify the solubility of CO2 in ionic liquids revealed a significant influence of the ionic liquid’s water content on the CO2 solubility. While water-saturated [BMIM][PF6] (up to 2.3 wt% water) has a CO2 solubility of only 0.13 mol fraction, 0.54 mol fraction CO2 dissolves in dry [BMIM][PF6] (about 0.15 wt% water) at 57 bar and 40 °C [7]. Kazarian et al. used ATR-IR to determine the solubility of CO2 in [BMIM][PF6] and [BMIM] [BF4]. They reported a solubility of 0.6 mol fraction CO2 in [BMIM][PF6] at 68 bar and 40 °C [8].

5.4.2

Catalytic Reaction with Subsequent Product Extraction

The first application involving a catalytic reaction in an ionic liquid and a subsequent extraction step with scCO2 was reported by Jessop et al. in 2001 [9]. These authors described two different asymmetric hydrogenation reactions using [Ru(OAc)2(tolBINAP)] as catalyst dissolved in the ionic liquid [BMIM][PF6]. In the asymmetric hydrogenation of tiglic acid (Scheme 5.4-1), the reaction was carried out in a [BMIM][PF6]/water biphasic mixture with excellent yield and selectivity. When the reaction was complete, the product was isolated by scCO2 extraction without contamination either by catalyst or by ionic liquid.

In a similar manner, the asymmetric hydrogenation of isobutylatropic acid to afford the anti-inflammatory drug ibuprofen has been carried out (Scheme 5.4-2). Here, the reaction was carried out in a [BMIM][PF6]/MeOH mixture, again followed by product extraction with scCO2 (see Section 5.2.4.1 for more details on these hydrogenation reactions).

5.4.3

Catalytic Reaction with Simultaneous Product Extraction

More recently, Baker, Tumas, and co-workers published catalytic hydrogenation reactions in a biphasic reaction mixture consisting of the ionic liquid [BMIM][PF6] and scCO2 [10]. In the hydrogenation of 1-decene with Wilkinson’s catalyst [RhCl(PPh3)3] at 50 °C and 48 bar H2 (total pressure 207 bar), conversion of 98 %

[BMIM][PF6], H2O 25°C/ 5bar

after reaction: extraction with scCO2

Scheme 5.4-1: Asymmetric, Ru-catalyzed hydrogenation of tiglic acid in [BMIM][PF6] followed by extraction with scCO2.

Scheme 5.4-2: Synthesis of ibuprofen by asymmetric, Ru-catalyzed hydrogenation in [BMIM][PF6] with product isolation by subsequent extraction with scCO2.

after 1 h was reported, corresponding to a turnover frequency (TOF) of 410 h–1. Under identical conditions, the hydrogenation of cyclohexene proceeded with 82 % conversion after 2 h (TOF = 220 h–1). The isolated ionic catalyst solution could be recycled in consecutive batches up to four times. The fact that a biphasic hydrogenation of 1-decene can be successfully achieved is not, however, any special benefit of the unconventional [BMIM][PF6]/scCO2 biphasic system. In fact, no reactivity advantage with the use of scCO2 in place of a more common alkane solvent for such a biphasic system can be concluded from the reported results.

5.4.4

Catalytic Conversion of CO2 in an Ionic Liquid/scCO2 Biphasic Mixture

In the same paper [10], the authors described the [RuCl2(dppe)]-catalyzed (dppe = Ph2P-(CH2)2-PPh2) hydrogenation of CO2 in the presence of dialkylamines to obtain N,N-dialkylformamides. The reaction of di-n-propylamine in the [BMIM][PF6]/scCO2 system resulted in complete amine conversion to provide the desired N,N-di-n-propylformamide with high selectivity. This compound showed very high solubility in the ionic liquid phase, and complete product isolation by extraction with scCO2 proved to be difficult. However, product extraction with scCO2 became possible once the ionic catalyst solution had become completely saturated with the product.

5.4.5

Continuous Reactions in an Ionic Liquid/Compressed CO2 System

Cole-Hamilton and co-workers demonstrated the first flow apparatus for a continuous catalytic reaction using the biphasic system [BMIM][PF6]/scCO2 [11]. They investigated the continuous Rh-catalyzed hydroformylation of 1-octene over periods of up to 33 h using the ionic phosphine ligand [PMIM]2[PhP(C6H4SO3)2] ([PMIM] = 1-methyl-3-propylimidazolium). No catalyst decomposition was observed during the period of the reaction, and Rh leaching into the scCO2/product stream was less than 1 ppm. The selectivity for the linear hydroformylation product was found to be stable over the reaction time (n/iso = 3.1).

During the continuous reaction, alkene, CO, H2, and CO2 were separately fed into the reactor containing the ionic liquid catalyst solution. The products and uncon-

284 Peter Wasserscheid

verted feedstock were removed from the ionic liquid still dissolved in scCO2. After decompression the liquid product was collected and analyzed. A schematic view of the apparatus used by Cole-Hamilton et al. is given in Figure 5.4-1.

Obviously, the motivation to perform this hydroformylation reaction in a continuous flow reactor arose from some problems during the catalyst recycling when the same reaction was first carried out in repetitive batch mode. In the latter case, ColeHamilton et al. observed a continuous drop of the product’s n/iso ratio from 3.7 to 2.5 over the first nine runs. Moreover, the isomerization activity of the system increased during the batch-wise recycling experiments, and Rh leaching became significant after the ninth run. The authors concluded from 31P NMR investigations that ligand oxidation due to contamination of the systems with air (during the opening of the reactor for recycling) had resulted in the formation of [RhH(CO)4] as the active catalytic species. This compound is known to show more isomerization activity and a lower n/iso ratio than the phosphine-modified catalyst system. Moreover, [RhH(CO)4] is also known to display some solubility in scCO2, which explains the observed leaching of rhodium into the organic layer.

All the problems associated with the batch-wise catalyst recycling could be convincingly overcome by application of the continuous operation mode described above. The authors concluded that continuous flow scCO2/ionic liquid biphasic systems provided a method for continuous flow homogeneous catalysis with integrated separation of the products from the catalyst and from the reaction solvent. Most interestingly, this unusual continuous biphasic reaction mode enabled the quantitative separation of relatively high boiling products from the ionic catalyst solution under mild temperature conditions and without use of an additional organic extraction solvent.

Slightly later, and independently of Cole-Hamilton’s pioneering work, the author’s group demonstrated in collaboration with Leitner et al. that the combination of a suitable ionic liquid with compressed CO2 can offer much more potential for homogeneous transition metal catalysis than only being a new procedure for easy product isolation and catalyst recycling. In the Ni-catalyzed hydrovinylation of

product collector

Figure 5.4-1: Continuous flow apparatus as used for the hydroformylation of 1-octene in the biphasic system [BMIM][PF6]/scCO2

5.4 Multiphasic Catalysis with Ionic Liquids in Combination with Compressed CO2 285

styrene it was possible to activate, tune, and immobilize the well-known Wilke complex by use of this unusual biphasic system (Scheme 5.4-3). Obviously, this reaction benefits from this special solvent combination in a new and highly promising manner.

Hydrovinylation is the transition metal-catalyzed co-dimerization of alkenes with ethene yielding 3-substituted 1-butenes [12]. This powerful carbon–carbon bondforming reaction can be achieved with high enantioselectivity by the use of Wilke’s complex as a catalyst precursor [13]. In conventional solvents, this pre-catalyst needs to be activated with a chloride abstracting agent, such as Et3Al2Cl3. Leitner et al. reported the use of Wilke’s complex in compressed CO2 (under liquid and under supercritical conditions) after activation with alkali salts of weakly coordinating anions such as Na[BARF] ([BARF]– = [(3,5-(CF3)2C6H3)4B]–) [14].

At first, the reaction was investigated in batch mode, by use of different ionic liquids with weakly coordinating anions as the catalyst medium and compressed CO2 as simultaneous extraction solvent. These experiments revealed that the activation of Wilke’s catalyst by the ionic liquid medium was clearly highly dependent on the nature of the ionic liquid’s anion. Comparison of the results in different ionic liquids with [EMIM]+ as the common cation showed that the catalyst’s activity drops in the order [BARF]– > [Al{OC(CF3)2Ph}4]– > [(CF3SO2)2N]– > [BF4]–. This trend is consistent with the estimated nucleophilicity/coordination strength of the anions.

Interestingly, the specific environment of the ionic solvent system appears to activate the chiral Ni-catalyst beyond a simple anion-exchange reaction. This becomes obvious from the fact that even the addition of a 100-fold excess of Li[(CF3SO2)2N] or Na[BF4] in pure, compressed CO2 produced an at best moderate activation of Wilke’s complex in comparison to the reaction in ionic liquids with the corresponding counter-ion (e.g., 24.4 % styrene conversion with 100-fold excess of Li[(CF3SO2)2N], in comparison to 69.9 % conversion in [EMIM][(CF3SO2)2N] under otherwise identical conditions).

*

Wilke’s catalyst

+ C2H4 ionic liquid/

compressed CO2

Scheme 5.4-3: The enantioselective hydrovinylation of styrene with Wilke’s catalyst.