Ionic Liquids

Molten salts with melting point below 100 °C are defined as ionic liquids (ILs) and they are in most cases formed by 1,3-N,N-dialkylimidazolium, N-alkylpyridinium

Ar = Ph, 2-Naphtyl, 2-Furyl, 4-Cl-Ph, 4-F-Ph,4-(C F3 )-Ph

Ar = Ph, 2-Naphtyl, 2-Furyl, 4-Cl-Ph, 4-F-Ph,4-(C F3 )-Ph

Scheme 3.10 Chiral Bronsted acid catalysis in water

o

0 N

| Ry

X-

X-

Rz

Rz

[EMIm]+ R = Et [BMIm]+ R = Bu

[N*yzw] + x>y>z>w

[P xyzw[ x>y>z>w

[HMIm]+ R = C6H13

X- = Cl-, no3-, bf4-

PF6-, CF3SO3-, CF3CO2-, NTf2-

miscibility with water miscibility with water

PFg" , NTf2- immiscible [RMIm]X increasing alkyl chain lenght-»- decreased miscibility viscosity

Scheme 3.11 Structures of the more common ionic liquids or tetraalkyl- ammonium and phosphonium cations combined with either organic or inorganic anions. Their negligible vapour pressure accounting for the lack of release in the atmosphere in contrast to common organic solvents makes them very attractive as sustainable alternative in organic synthesis. Moreover, ILs are non-inflammable, thermally and chemically stable, display high density and viscosity, high conductivity and low dielectric constant as well as unique solvating properties through hydrogen-bonding, p-p, electrostatic and hydrophobic interactions [76]. Remarkably, physicochemical properties of ILs can be tailored through proper choice of cations and anions offering the possibility to design task specific compounds with broader versatility with respect to organic solvents. For example, non-symmetrical N,N-dialkylimidazolium cations give ILs with lower melting point whereas the nature of anion has a marked impact on viscosity and water solubility. Salts with halide anions, BF-, CF3SO-, CF3COO-, but not PF- or NTf—, are fully miscible with water whereas solubility in organic solvents can be finely tuned by modification of the length of alkyl chains on the imidazolium cation (Scheme 3.11).

Besides their use as solvents in a wide variety of organic reactions either in homogeneous or heterogeneous systems [77], ILs have found interesting applications as heat-transfer fluids, in chromatographic and electrophoretic separations [78], selective extractions [79], electrochemistry [80] and polymer science [81]. Although a significant collection of data has been set up in last decade regarding the synthesis of ILs and purification methods [82], the relationships between structure and solubility parameters [83], the influence of impurities and additives on physical properties [84], questions on their modes of toxicity and bioaccumulation remain still to be better investigated. From a number of ecotoxicity tests carried out on different bacterial strains or aquatic organisms and recently reviewed by Seddon et al. [85] it appeared evident that toxicity of ILs cannot be systematically estimated by the sum of effects of the cation and anion and, considering the immense diversity of possible formulations, a generalisation of ILs as entirely ''green'' or ''toxic'' solvents could be misleading.

Due to their cost, the synthetic efforts required for their preparation and their persistance in the environment, the use of ILs in green chemistry finds justification in conjunction with their efficient recycle and in the majority of synthetic applications the choice or ''design'' of a suitable IL has also allowed the selective separation of products and residual reactants by extraction with organic solvent or supercritical CO2 (scCO2). In this context, biphasic systems with scCO2 appear very promising since ILs do not dissolve in this fluid so that cross-contamination is avoided and pure products can be recovered [86] while ILs can be reused after addition of fresh reactants.

The development of catalysts ''pseudo-immobilised'' in the IL phase offers a general strategy for simultaneous recycle of catalysts and solvent with direct cost reduction but also many unmodified transition-metal precursors and their chiral complexes as well as proline and prolinamides display good solubility in ILs. In such instances, satisfactory recovery of catalysts can be achieved by extraction from biphasic organic solvents/ILs mixtures and a variety of asymmetric reactions has been performed without the need of specially designed ligands [87-89].

In the first report of asymmetric alkene hydrogenation with BINAP-Ru(II) complex in i-PrOH/[BMIm][BF4] 10:1 mixture, the enantioselectivity was found comparable with that obtained in pure alcohol and constant catalyst performances were maintained in four recycle runs [90]. In the hydrogenation of tiglic acid with the same catalyst, the enantioselectivity was found H2-pressure dependent (low H2 pressure and mass transfer rates for optimum selectivity) and, among different ILs, neat [BMIm][PF6] was the best reaction medium for its higher viscosity, that provided lower concentration of dissolved H2 [91]. When the carbonyl hydrogenation of methylacetoacetate was carried out in [NR222][NTf2]/MeOH 1:1 mixtures, both enantioselectivity and activity of BINAP-Ru(II) complex were

COOH NHAc -

COOH NHAc -

Cl^X0

>99% ee after 10 cycles

38 (1.2% mol) InCl3 (10% mol) AgSbF6 (20% mol) [C6MIm][PF6]/DCE 1:1

F3COH

F3COH

38 (1.2% mol) InCl3 (10% mol) AgSbF6 (20% mol) [C6MIm][PF6]/DCE 1:1

Scheme 3.12 Transition-metal catalyzed reactions in ionic liquids

influenced by the length of the R alkyl chain in the ammonium cation and excellent results were obtained with dodecyl substituent [92].

Catalyst Rh[Me-DuPHOS] 36 in [BMIm][PF6] or in [BMIm][BF4]/sCO2 homogeneous phase was effective in the hydrogenation of methyl-a-acetamido cinnamate [93, 94] and the reaction was also exploited in the design of a novel process for industrial preparation of Levodopa starting from related substrate 35b (Scheme 3.12a). The hydrogenation was optimized using 1-butyl-3-methylpyrro-lidinium octylsulphate, as more stable and biodegradable reaction medium, whereas the product separation and recycle of catalyst in the IL phase were ensured by sCO2 extraction. Moreover, the IL provided sensible stabilization of the air-sensitive rhodium catalyst thus extending its recyclability. Combining these two alternative solvents, notable reductions in the amounts of deactivated catalyst and solvent (120-fold and 90-fold, respectively) were estimated in comparison with the conventional process in MeOH [95].

Coupling of ILs with sCO2 extraction has been also advantageously exploited in asymmetric dihydroxylation of trans-cinnamoyl methyl ester with the classical Cinchona alkaloid/Os-catalysts and [C8MIm][PF6] was found optimal in

O Ph

0 0

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