4.

Novel reaction media: ionic liquids

Organisch-Chemisches Praktikum II, 2011

4. Novel reaction media Ionic liquids

Literature: P. Wasserscheid, T. Welton, Eds., Ionic Liquids in Synthesis, 2nd ed., Wiley-VCH, 2007, Weinheim. Characteristics definition: salts with melting points mp < 100 C (typically at or below 25 C) upper limit of liquid range: 350 C (decomposition) extremely low vapor pressure common cations:

R1

R2

NR4 R

common anions: BF4, PF6, AlCl4, TfO

4. Novel reaction media: ionic liquids

Organisch-Chemisches Praktikum II, 2011

Synthesis and purification quaternization of N-base as first step: facile reaction with RHal various methods for generating complex anions X: a) addition of AlCl3:
N N Cl CH3 AlCl3 Et N N Cl CH3 Cl Al Cl Cl

Et

[Emim]+Cl

[Emim]+AlCl4, moisture-sensitive

b) anion metathesis: [Emim]+Cl + AgBF4 [Emim]+BF4 + AgCl c) use of anion exchange resin d) addition of HX or MX: works only for water immiscible ionic liquids (HHal or MHal can be washed out) purification: a) washing steps with water and/or apolar organic solvents b) drying under vacuum at elevated temperature

4. Novel reaction media: ionic liquids

Organisch-Chemisches Praktikum II, 2011

Correlation of structure and melting point melting point decreases as a function of anion size (no strict correlation) X Cl BF4 PF6 AlCl4 r/pm 170 220 240 280 mp(NaX) in C 801 384 > 200 185 mp([Emim]+X]) in C 87 6 60 7

similar trend for cation size lower melting points for asymmetric cations explanation: reduced Coulomb interactions

4. Novel reaction media: ionic liquids

Organisch-Chemisches Praktikum II, 2011

Polarity of ionic liquids

r [Pr2NH2]+SCN [Emim]+TfO [Emim]+BF4 [Bmim]+BF4 [Bmim]+TfO [Bmim]+PF6 11.4 15.2 12.8 11.7

ETN 1.006 high polarity, but only 0.673 0.667 0.667 weakly coordinating anions

ionic liquids typically immiscible with apolar solvents poor solubility of hydrocarbons ionic liquids typically miscible with polar solvents (miscibility with water depends on hydrophobicity of cation) hygroscopic

4. Novel reaction media: ionic liquids

Organisch-Chemisches Praktikum II, 2011

Characteristics of ionic liquids as reaction media strong interactions between cations and anions (some authors propose formation of a 3-dimensional network): bringing the reactants together may cost energy in contrast, approach of the reactants often entropically less demanding than in less-ordered molecular liquids constituents of ionic liquids may actively participate in reaction small concentrations of simple molecules, such as H2O, may change properties of ionic liquids

4. Novel reaction media: ionic liquids

Organisch-Chemisches Praktikum II, 2011

Practical aspects of ionic liquids extremely low vapor pressure minimizes fire hazard extremely low vapor pressure permits product separation by distillation immiscibility of ionic liquids with apolar organic solvents often permits product separation by extraction catalyst immobilization in ionic liquid and recycling often possible polar by-products may accumulate in ionic liquid and compromise its performance high costs of ionic liquids so far only few commercial applications in organic synthesis

4. Novel reaction media: ionic liquids

Organisch-Chemisches Praktikum II, 2011

Diels-Alder reactions in ionic liquids faster reactions than in Et2O, but similar to those in H2O relatively high endo/exo selectivity 1st explanation: solvophobic effect (internal pressure): apolar reactants are forced together facilitation of association and formation of transition structure

2nd explanation: imidazolium cations act as Lewis acids

CH3 H3CO O H N R R N X X H N

CH3 N

+ reactants

Lewis basicity of anion affects endo/exo selectivity

4. Novel reaction media: ionic liquids

Organisch-Chemisches Praktikum II, 2011

Electrophilic substitutions common: use of chloroaluminate ionic liquids with an excess of AlCl3 (well soluble) works well for Friedel-Crafts alkylation and acylation reactions separation of polar products (such as ketones) from ionic liquid difficult: often aqueous work-up and destruction of ionic liquid necessary nitration and halogenation reactions have also been reported

4. Novel reaction media: ionic liquids

Organisch-Chemisches Praktikum II, 2011

Reactions catalyzed by transition-metal complexes transition-metal complexes often well soluble in ionic liquids use for a) hydrogenation (Rh, Ru catalysis), b) Heck (Pd catalysis), and c) cross-coupling (Pd catalysis) reactions imidazolium cations may act as precursors for in-situ formed carbene ligands:
2H 2 R N H N Br 2 CH3 R N N + 2 Br CH3 H3C Pd(II) N Br N Pd N Br N R

CH3

deprotonation

N H

CH3

+ Pt(PPh3)4

2 PPh3 R N Pt H N CH3

oxidative addition

Ph3P

PPh3