Ionic liquids are compatible with on-water catalysis

A major limitation of on-water catalysis has been the need for liquid reactants to enable emulsification. We demonstrate that ionic liquids are compatible with on-water catalysis, enabling on-water catalysed reactions for otherwise unreactive solid-solid systems. The unique solvation properties of ionic liquids dramatically expands the scope of on-water catalysis.


General Experimental Details:
All solvents and reagents were used as received from commercial sources.Water was purified using a Millipore Milli-Q System (<18.2 MΩ.cm @25°C) or Millipore Elix system (< 15 MΩ.cm @25°C).Melting points were determined using a Stanford Research Systems Optimelt automated melting point system and are uncorrected.Infrared spectra were acquired neat on a Bruker Alpha-E ATR spectrometer. 1 H and 13 C NMR spectra were recorded on a Bruker ASCEND 500 ( 1 H frequencies 500 MHz; 13 C frequencies 125 MHz), a Bruker AVANCE DPX300 ( 1 H frequencies 300 MHz; 13 C frequencies 75 MHz) or a Bruker AVANCE DPX200 ( 1 H frequencies 200 MHz; 13 C frequencies 50 MHz). 1H chemical shifts are expressed as parts per million (ppm) with residual chloroform (δ 7.26) as reference and are reported as chemical shift (δ Η ); relative integral; multiplicity (s singlet, br broad, d doublet, t triplet, dd doublet of doublets, dt doublet of triplets, q quartet, m multiplet); and coupling constants (J ) reported in Hz. 13 C NMR chemical shifts are expressed as parts per million (ppm) with residual chloroform (δ 77.1) as internal reference and are reported as chemical shift (δ C ); multiplicity (assigned from DEPT experiments).High resolution mass spectra were recorded on a Bruker ApexII Fourier Transform Ion Cyclotron Resonance mass spectrometer with a 7.0 T magnet, fitted with an off-axis Analytical electrospray source.

General Procedures for Cycloaddition Reactions:
All reactions were conducted in duplicate (or triplicate) and % conversion was calculated as [integral product]/([integral product] + [integral starting material]) determined by 1 H NMR analysis of the crude reaction mixture.

On-Water:
A suspension of the diene/dipole (0.5/0.3 mmol) and the dienophile/dipolarophile (0.5/0.3 mmol) in water (4 mL) was stirred vigorously at the prescribed temperature (80 o C, 40 o C or room temperature) for the stated time.The reaction was extracted with ethyl acetate (4 mL) and the organic phase concentrated under reduced pressure.

At-Water:
A suspension of the diene/dipole (0.5/0.3 mmol) and the dienophile/dipolarophile (0.5/0.3 mmol) in water (4 mL) was stirred gently (ca 250 r.p.m) at the prescribed temperature (80 o C, 40 o C or room temperature) for the stated time.The reaction was extracted with ethyl acetate (4 mL) and the organic phase concentrated under reduced pressure.

Neat:
The diene/dipole (0.5/0.3 mmol) and the dienophile/dipolarophile (0.5/0.3 mmol) were stirred neat at the prescribed temperature (80 o C, 40 o C or room temperature) for the stated time.The reaction was concentrated in vacuo where appropriate to remove the unreacted volatile components.

On-Water/IL:
A suspension of the diene/dipole (0.5/0.3 mmol) and the dienophile/dipolarophile (0.5/0.3 mmol) in water (4 mL) and [BMIM][NTf 2 ] (0.5 mL) was stirred vigorously at the prescribed temperature (80 o C, 40 o C or room temperature) for the stated time.The reaction was extracted with ethyl acetate (4 mL) and the organic phase concentrated under reduced pressure.
On-Water/Solvent: A suspension of the diene/dipole (0.5/0.3 mmol) and the dienophile/dipolarophile (0.5/0.3 mmol) in water water (4 mL) and organic solvent (0.5 mL, toluene or hexadecane) was stirred vigorously at the prescribed temperature (80 o C, 40 o C or room temperature) for the stated time.The reaction was extracted with ethyl acetate (4 mL) and the organic phase concentrated under reduced pressure.Freshly distilled cyclopentadiene (33 μL, 0.40 mmol) was added to a suspension of dimethyl fumarate (50 mg, 0.35 mmol) in water (4 mL) and the suspension was stirred vigorously for 150 minutes.Ethyl acetate (10 mL) was added and the phases were separated, the organic phase was dried over Na 2 SO 4 and the solvent was evaporated to give the title compound (68.3 mg, 93%) as colourless oil.ν max (neat)/cm
The dipole is very insoluble in most NMR solvents, so the reaction mixtures were diluted with ethyl acetate (4 mL), filtered and concentrated in vacuo.The percentage conversion was calculated relative to the remaining maleimide.
Additionally, the remaining insoluble dipole was collected after 6 hours, and the mass recovery was compared with the conversion by 1 H NMR analysis.

Solvent % conversion (by mass) % conversion (by NMR)
On-water 75-80% 76% Neat 80-85% 82% For both the on-water and neat reactions, the percentage conversion calculated by mass balance and by NMR was consistent; indicating that calculating conversion by NMR was a valid method.
Following the general procedure (On-Water/IL), a mixture of 9-anthracenemethanol (104 mg, 0.50 mmol) and dimethyl fumarate (72 mg, 0.50 mmol) in water (4.0 mL) and [BMIM][NTf 2 ] (0.5 mL) was stirred vigorously at 80 o C for 20 h.The resulting mixture was extracted with EtOAc (5 mL) and the organic phase concentrated under reduced pressure.The residue was extracted repeatedly with toluene (5 × 1 mL) to give the IL, which was dried under vacuum and used in subsequent cycles without further purification.The organic extracts were concentrated under reduced pressure to give a mixture of the Diels-Alder adduct and starting materials and analysed by 1 H NMR.

Table ESI - 1 .
Effect of varying the amount of ionic liquid in the emulsion.

Table ESI - 4 .
4omparison of endo:exo selectivity as a function of solvent.4