Ionic Liquids

in
Organic Synthesis
Adam M. Azman
15 November 2006
15 November 2006

Ionic Liquids

AMA 1

What is an Ionic Liquid?

Any salt above its melting point
Technically, all molten salts, such as NaCl
(mp = 800oC), are ionic liquids
Obviously not practical for organic synthesis

15 November 2006

Ionic Liquids

AMA 2

What is an Ionic Liquid?

Definitions from Literature

The term ionic liquid implies a material that is fluid at (or close to) ambient temperature, is colorless,
has a low viscosity and is easiliy handled. (Sheldon)
Room temperature ionic liquids are generally salts of organic cations, e.g. tetraalkylammonium,
tetraalkylphosphonium, N-alkylpyridinium, 1,3-dialkylimidazolium and trialkylsulfonium cations.
(Sheldon)
Most basic definition of a room temperature ionic liquid is a salt that has a melting point at or near
room temperature. (Handy)
Organic salts with melting points below ambient or reaction temperature. (Maio)
Ionic liquid is a salt with a metling temperature below the boiling point of water. (Wilkes)

Salt of organic cation which has a

melting point near ambient
temperature (up to ~100oC)
H
Al2 Cl7

AlCl3
N Cl

R
H

Et 3 NHCuCl2

N
PF6

15 November 2006

Ionic Liquids

AMA 3

Synonyms for Ionic Liquids

Ionic Liquid (IL)

Room temperature ionic liquid (RTIL)
Molten salt
Room temperature molten salt
Ambient temperature molten salt/ionic liquid
Task specific ionic liquid (TSIL)
Liquid organic salt
Fused salt
Neoteric solvent

15 November 2006

Ionic Liquids

AMA 4

(very)

1800s So called red oil formed during Friedel-Crafts reactions

AlCl3
N

Melting point = 40 C, butylpyridinium cation easily reduced

Cl-

Large, asymmetric anions should lower melting point, as should large, asymmetric cations

Imidazolium theorized to be excellent candidate (experimentally true)

Imidazolium cation more stable to reduction, melting point below room temperature

R N

N R

Chloroaluminate salts are reactive to water not a problem for batteries

Thermal batteries have molten salt electrolyte (LiCl-KCl)

Reaches temperatures between 375-550oC

1970s Fast computer method (1 week) for predicting electrochemical

properties of ammonium salts

Al2 Cl7 -

It was noticed that large anions with many degrees of freedom inhibited
crystalization until lower temperature

R
H

Ethylammonium nitrate (1914) has melting temperature of 12oC

Used as liquid propellants for naval guns

Start of modern era of ionic liquids began with discovery of 1butylpyridinium chloride-aluminum chloride mixture

Identified as long presumed intermediate called sigma complex

1960s-Present Air Force Academy has continuous research effort for

ionic liquds for thermal batteries

Early 1900s - Alkylammonium nitrates found to be liquids at room

temperature

Brief History of Ionic Liquids

Early 1990s Ethylmethylimidazolium halides prepared, then anion metathesis with various silver
salts provided a small library of room temperature ionic liquids

Late 1990s-Present (and beyond) Envelope (as always) being pushed

Exotic anions, functionalized cations, functionalized anions, chiral cations/anions,

Limitless possibilities of new ionic salts to fill every niche of chemistry

15 November 2006

Ionic Liquids
Wilkes, J. S. Green Chemistry, 2002, 4, 73-80

AMA 5

Properties

Non-flammable
Negligible vapor pressure
High thermal/chemical/electrochemical stability
Solvating ability
Large liquidus range (span of temperatures between melting and
boiling point of a liquid)
Easy recyclability
Highly polar
Non-coordinating
Tunable miscibility with water or organic solvents
Generally do not coordinate with metals, enzymes
Able to be stored for long time without decomposition
Chiral ionic liquids may control stereoselectivity
Pure imidazolium ionic liquids can be described as polymeric hydrogenbonded supramolecules and in some cases when mixed with other
molecules, they should better be regarded as nonstructured materials with
polar and non polar regions rather than homogeneous solvent. (Dupont)

15 November 2006

Ionic Liquids

AMA 6

Properties

Stability/Thermal decomposition
Imidazolium cation stable above 300oC
Decomposition: cleavage of C-N bond between imidazole nitrogen and alkyl
chain
Anion plays a role
Less nucleophilic higher stability

Density

Least effected by temperature variation or impurity

All greater than 1 for imidazolium cation
Lengthening alkyl chain lower density
Increasing halogen content higher density

Viscosity
Even least viscous room temperature ionic liquids are quite viscous
compared to conventional solvents
Highly sensitive to temperature and impurities
Short alkyl chain/functionalized alkyl chain lower viscosity
Longer alkyl chain increased van der Waals forces increased energy required
for molecular motion

BF4- anion causes lower viscosity than PF6- anion

Conductivity

Inversely parallels viscosity

15 November 2006

Ionic Liquids

AMA 7

The Cation
Infinite in number
Most common:

Dialkylimidazolium N N
N R
Alkylpyridinium
R
Tetraalkylammonium R N R R
R
Tetraalkylphosphonium R PR R

Can be tuned to properties needed

For liquid at room temperature, should be
unsymmetrical
Functionalizing side chain on cation can change melting
point of straight-chain relative
Presence of C2-methyl group generally increases melting
point of unsubstituted relative
Substituting at C4 has little effect on melting point
15 November 2006

Ionic Liquids

AMA 8

The Anion
Much diversity
Common:

F
F B- F

Tetrafluoroborate
F
Hexafluorophosphate FF P FF
F
Bis(trifluoromethanesulfonyl)imide
Halogen
Mesylate/tosylate/triflate
F

O S
O

O
F
F

OO
O
S
F
N
F F
F

O S
O

O F
-

O S
F
O F

Larger, more weakly coordinating anion

lower melting temperature

15 November 2006

Ionic Liquids

AMA 9

Melting Point Variation

BF4

Melting point for R Methyl Imidazolium Cation with Varying Anion

Br
Cl

250

Me N

Ms
NTf2

200

R methyl imidazolium cation

[Rmim][X]

PF6
Melting Point (deg C)

N R
X-

Tf

150
100
50
0
0

10

12

14

16

18

20

-50
-100
Le ngth of Alkyl Cha in (# Ca rbon Atom s)

Melting Points for Symmetrical Ionic Liquids (PF6 Anion)

120
100

Melting Point (deg C)

80

R N

N R
PF6 -

symmetrically substituted
imidazolium cation
[RRim][PF6 ]

15 November 2006

Ionic Liquids

60
40
20
0
-20 0

-40
-60
-80
-100
# Carbon atoms (per side)

AMA 10

10

Partial Miscibility Chart

(R Methyl Imidazolium Cation)

15 November 2006

Ionic Liquids

AMA 11

Other Ionic Liquid Cations

Pyridinium
Possibly unstable in presence of nucleophiles
Alkyl chain length effect on melting point mirrors
imidazolium

Tetraalkylammonium
Known for much longer than imidazolium
Highly viscous/difficult to handle
Long alkyl chain/decreased symmetry lower
melting point

Others
Triazolium, pyrazolium, thiazolium,
benzimidazolium
Guanidinium, phosphonium, sulfonium
15 November 2006

Ionic Liquids

AMA 12

Synthesis

15 November 2006

Ionic Liquids

AMA 13

Why do I care?

Problems with molecular solvents:

Grant money becoming more competitive

Chemical bunker a real inconvenience
Toxic/hazardous properties of solvents, notably chlorinated hydrocarbons
Expensive catalysts
Strong acids
High temperatures
Long reaction times
Possible cumbersome isolation procedures
Other drives to anchor catalyst for recovery/reuse require additional
catalyst/enzyme modification
Steric hindrance causes decrease in efficiency of reaction

Solutions with ionic liquids:

Combine best advantages of molten salts and avoid worst disadvantages
caused by high temperatures
Two phase system allows product in one phase, everything else in other
phase
Ionic liquid immobilizes catalyst/reagent for recycling and reuse
Ionic liquids can act as solvent and catalyst in some systems without
need for additional catalyst or ligand
Rate acceleration effect on some catalytic reactions

15 November 2006

Ionic Liquids

AMA 14

Limitations

A dearth of information on biodegradability and toxicity

Cannot be purified by distillation
Trace impurities can have significant impact on physical properties
must be initially produced in high purity
Some ionic liquids are prone to hydrolysis especially in reactions
involving metals
C2 hydrogen relatively acidic (pKa = 21-23)

Deprotonation generates N-heterocyclic carbene

Good ligand for metal complexes

Oxidative addition to electron-rich Ni0 or Pd0 to generate

(carbene)metal hydride compounds
Decomposition possible under sonochemical conditions

Creates hot spots in solvent

May limit ultrasound- and microwave-assisted processes

15 November 2006

Ionic Liquids

AMA 15

Applications

Storage media for toxic gases

Lubricants
Performance additives in pigments
Propellants
Organic chemistry:
Hydrogenation

Wittig

Hydroformylation

Robinson annulation

Alkoxycarbonylation

Dihydroxylation

Cross coupling (Heck, Suzuki, Negishi, Stille)

Alcohol oxidation

Allylic substitution

Friedlander reaction

Friedel-Crafts alkylation

Nitration of phenols

Diels-Alder

Bromination of aromatics/alkynes

Diol/carbonyl protection

Cyclopropanation

Epoxidation/Epoxide opening

Synthesis of 2,4,5-triaryl imidazoles

Cyanosilyation of aldehydes

Synthesis of 3,4-dihydropyrimidin-2(1H)ones

Esterification

Dimer-/Oligomer-/Polymerization

Ring closing metathesis

Chiral solvent for asymmetric synthesis

Knoevenagel condensation
Baylis-Hillman
15 November 2006

Kinetic resolution
Ionic Liquids

Biocatalysis

AMA 16

Diol/Carbonyl Protection
R3
O
R1

HO

R3

OH

[Hmim][BF4 ]
90 C

R1

R2

HN

N Me
BF4 -

[Hmim][BF4-]

In molecular solvents large excess of reagents

Monosubstituted imidazolium ionic liquids serve as Brnsted acids
Acidic ionic liquids afford protected product with:

R2

O O

No added catalyst
1:1 ratio of carbonyl to diol
No refluxing/Dean-Stark trap
No molecular solvent
Recyclable catalyst

Acetals immiscible with ionic liquid no need to remove water

15 November 2006

Ionic Liquids
Wu, H-H.; Yang, F.; Cui, P.; Tang, J.; He, M-Y. Tetrahedron Lett., 2004, 45, 4963-4965.

AMA 17

Diol/Carbonyl Protection
R3
O
R1
C a rb o ny l

HO

R2
A lc oh o l

R3

O O
OH

[H m im ][B F 4]
9 0 C

M o la r R ati o Ti me (h )

R1

R2

Se l ec ti vi ty (% )

C on ve rs io n (% )

O
n

hex

HO

OH

1:1

100

98

HO

OH

1:1

3 .5

100

100

HO

OH

1:1

100

93

HO

OH

1:1

100

76

1:1

100

93

1:1

100

100

OH

1:1

100

97

OH

1:1

100

94

OH

1:1

100

OH

1:2

100

100

OH

1:2

100

60

OH

1:2

100

100

O
O

O
O
Ph

H
O
H

HO

OH

HO

OH

HN

BF 4 -

[Hm im ][BF 4 ]

NO 2
O
nh e x

HO

O
HO
O
HO
O

HO

O
Ph

HO

H
O
H

HO

92

92

94

94

94

95

94

95

94

NO 2

15 November 2006

Ionic Liquids
Wu, H-H.; Yang, F.; Cui, P.; Tang, J.; He, M-Y. Tetrahedron Lett., 2004, 45, 4963-4965.

AMA 18

Friedlander Synthesis
O

R1
R1

O
R2

R2

R3

NH 2

Common additives: HCl, H2SO4, PTSA, microwave, ZnCl2/NEt3, ruthenium or

palladium complexes
Can be run in ionic liquid with no additive
Efficacy correlated to basicity of anions of ionic liquid
Bu N

N Bu
X-

[bbim][X]

HN

N Bu
X-

[Hbim][X]

R3

Ionic Liquid

pKa of Acid of Anion, HX

Yield (%)

[bbim][ClO4]
[bbim][Br]
[bbim][Cl]
[bbim][PF6]
[bbim][BF4]

-11
-9
-7

37
50
50
70
75

[Hbim][ClO4]
[Hbim][Br]
[Hbim][Cl]
[Hbim][PF6]
[Hbim][BF4]

-11
-9
-7

0.5

0.5

50
75
73.8
90
96

Ionic liquid can be recovered almost completely and recycled at least twice

15 November 2006

Ionic Liquids

Palimkar, S. S.; Siddiqui, S. A.; Daniel, T.; Lahoti, R. J.; Srinivasan, K. V.; J. Org. Chem., 2003, 68, 9371-9378.

AMA 19

Friedlander Synthesis

OH

OH

O
H

O
H

NH 2

NH 2
O
Me

H
O

N
H
N

N
H
N
H
O

N
O

Ar

15 November 2006

H
N N

Ionic Liquids
Muchowski, J. M.; Maddox, M. L.; Can. J. Chem., 2004, 82, 461-478.

AMA 20

O
H

Friedlander Synthesis
O

R1
R1

Co m po u nd 1

O
R2

NH2
C om p ou n d 2

A B -

R 1 =H,
R 1 =Cl,

R2

A
B

N H2
R 2 =Me
R 2 =Ph

O
OE t

N
R2

Me
O

OE t

R1

Me

Me

A
B

R2
R1

Me

[H b im ][BF 4 ]

Pro d u ct

O
R1

R2
R3

Me

N
Tim e (h )

A 94 93
B 94 94

93
93

3.3

A 94 94
B 93 93

93
91

N
Me
R2

HN

R1
3

A 96 95
B 97 96

94
95

A 96 96
B 98 96

94
96

A 97 96
B 97 95

95
95

A 94 94
B 93 92

93
91

N
R2

A 93 92
B 91 90

90
90

3.3

A 93 93
B 93 93

91
92

R1

A
B

N
R2

O
Me

Me

R1

Me
N
R2

Me

R1

Me

Ph
N

15 November 2006

[H b im ][BF 4 ]

R1

A
B

A
B

N Bu
BF 4-

R1
N
R2

A
B

Yi e ld (% )

N
R2
A
B

R3

Me

Ionic Liquids

Palimkar, S. S.; Siddiqui, S. A.; Daniel, T.; Lahoti, R. J.; Srinivasan, K. V.; J. Org. Chem., 2003, 68, 9371-9378.

AMA 21

Knoevenagel Condensation/
Robinson Annulation
EWG

EWG

EWG

O
R

EWG

Reactions performed in air without rigorous drying of ionic liquid

Product extracted with toluene
Ionic liquid washed with toluene and reused without further purification

15 November 2006

Ionic Liquids
Morrison, D. W.; Forbes, D. C.; Davis, Jr., J. H. Tetrahedron Lett., 42, 2001, 6053-6055.
Forbes, D. C.; Law A. M.; Morrison, D. W. Tetrahedron Lett., 47, 2006, 1699-1703.

AMA 22

Knoevenagel Condensation/
Robinson Annulation
O
EWG

R
M al on a te
D e riv ati ve

NC

[h ex mi m][PF 6 ]
22 h , 4 5 -5 5 C

C ar bo n yl
D e ri va tive
Cl

E WG

R
Yi e ld (% ) (u no p tim ize d )

Pr od u ct

CN

EWG

gl yci n e (0 .2 e q .)

E WG

CN

O
Cl

86

CN

CN

CN
O 2N

CN

77

CN

CN

CN

O
M eO

OH

74

H
NC

CN

O 2N

CN

PF 6-

g ly cin e

H
NC

n h ex

H 2N

H
NC

[h e xm im ][P F 6 ]

Cl

Cl

Me N

62

10 cycles
performed without
dropping below
90% conversion.

CN

Me O
H

NC

CN

CN

32

CN
O
O
EtO

15 November 2006

EtO

48

Me

Ionic Liquids
Morrison, D. W.; Forbes, D. C.; Davis, Jr., J. H. Tetrahedron Lett., 42, 2001, 6053-6055.
Forbes, D. C.; Law A. M.; Morrison, D. W. Tetrahedron Lett., 47, 2006, 1699-1703.

AMA 23

Hydrogenation

First example by Chauvin, 1995

Dupont showed RuCl2(Ph3P)3 in [bmim][BF4] has turnover number = 540 h-1

Metal complex recyclable

H2
C O 2H

C ata ly st

Su b stra te

i n s it u R u -(S )-BIN AP

[R uC l 2- (S)- BIN AP ]2 N Et 3
i n s itu R u -(R )-B IN A P

(S)

C O 2H

Ph
Ph

[R uC l 2- (S)- BIN AP ]2 N Et 3

Ph
(S)

1 st re cyc le

Ph

2 nd re cy cle

C O 2H

Ph

3r d re c ycl e

Ph
(S)

[R u -(S )-BIN AP ]
M eO

100

62 (S)

M e OH

100

83 (S)

i -PrO H

100

64 (S)

[b mi m][BF 4 ]/Me OH

100

86 (S)

[b mi m][B F 4]/i -P rOH

99

6 9 (R )

[b mi m][B F 4]/i -P rOH

99

7 2 (R )

[b mi m][B F 4]/i -P rOH

99

7 7 (R )

[b mi m][B F 4]/i -P rOH

99

7 0 (R )

[b mi m][B F 4]/i -P rOH

100

78 (S)

[b mi m][B F 4]/i -P rOH

100

84 (S)

[b mi m][B F 4]/i -P rOH

90

79 (S)

[b mi m][B F 4]/i -P rOH

95

67 (S)

[b mi m][B F 4]/i -P rOH

100

80 (S)

PH 2
PH 2

B INA P

(R)

3r d re c ycl e

M e OH

Ph

Ph

2 nd re cy cle

% ee

Ph

Ph

1 st re cyc le

C on v er sio n (% )

C O 2H

Ph

i n s itu R u -(R )-B IN A P

So l ve nt
Sy ste m

Pro d uc t

Ph

[R uC l 2- (S)- BIN AP ]2 N Et 3

* C O 2H

[R u- BIN AP ]
[b mi m][BF 4 ]/Org a n ic S ol ve nt

C O 2H

Me

N
B F 4-

[bm im ][B F 4 ]

M eO
(S)- Na p ro xe n

15 November 2006

Ionic Liquids

Monteiro, A. L.; Zinn, F. K.; de Souza, R. F.; Dupont, J. Tetrahedron: Asymmetry, 1997, 8, 177-179.

AMA 24

DielsAlder

Ionic liquid allows for catalyst recovery, rate acceleration, selectivity

enhancement
O

O
S c(OTf )3 ( 0.2 mo l% )
s ol ve n t, rt, 2 h

O
Yi el d ( % )
22
46
>99

S ol ve nt
C D 2 C l2
[bm im ][PF 6 ] ( 1 e q .) + C D 2 Cl 2
[bm im ][PF 6 ]
Di e no p hi le

Di e ne

Pr od u ct

Y ie ld (% )

>99 :1

94

[bmim][PF6 ]

O
-

94

>99 :1

96

80

>99 :1

84

>99 :1

71

86
83

81
87

88
89

86
91

85
90

O
O

O
O

O
O

O
O
O

N Bu
PF6 -

Me N

15 November 2006

En d o :ex o

O
O

Ionic Liquids

Song, C. E.; Shim, W. H.; Roh, E. J.; Lee, S.; Choi, J. H. Chem. Commun., 2001, 1122-1123.

AMA 25

Olefin Epoxidation

(R,R)-Jacobsens catalyst immobilized in ionic liquid

Rate enhancement noticed over molecular solvents
Enantioselectivity and activity decrease upon reuse possible catalyst
degredation over time
Co-solvent used for reactions below room temperature, because ionic liquid
solid at reaction temperature

H
N

N
Mn

t-Bu

O
t-Bu

Cl

t-Bu

t-Bu

(R,R)-Jacobsen's Catalyst

15 November 2006

Ionic Liquids

AMA 26

Olefin Epoxidation
R1

R3

(R, R)-Jacobsen's Catalyst

NaOCl

R2

R4

[bmim][PF 6]-CH2 Cl2

0 C

Substrate

Product

O
R1

R2

R3
R4
Me N

Time (h)

Yield (%)

% ee

86
73 73 60 53

96
90 90 89 88

72

94

N Bu
PF6 -

[bmim][PF 6]

O
O

O
NC

NC

O
4

72

Ph

84

t-Bu

O
Me

N
Mn

t-Bu

Ph

H
N
Cl

t-Bu

t-Bu

(R,R)-Jacobsen's Catalyst

Me
3

72

86

77

84

O
O

15 November 2006

Ionic Liquids
Song, C. E.; Roh, E. J. Chem. Commun., 2000, 837-838.

AMA 27

Heck Reaction

1996 First example in ionic liquid by Kaufmann

Used ammonium and phosphonium salts

Ph

Br
Pd

Under basic conditions, deprotonation and formation of palladium

Br
complexes of imidazolium carbenes facile
N
Me
Competition of cationic and neutral pathways for enol ethers nonexistent
in ionic liquids -arylation (cationic) regiospecific
+

Pd P
P
I

BuO

N
N
Me

IPh

OBu
P
Pd P

Ph

Ph

OBu

Pd P

OBu

Ph

BuO
Ph Pd P

P
Pd P

Ph

Ph

OBu

1999 Seddon found tri-phasic system organic: product, ionic liquid:

catalyst, aqueous: salt

Bu

OBu

Bu
N

Allows catalyst to be recovered and reused

Similar results for Suzuki, Stille, and Negishi (although yield decreases
on recycle experiments for Negishi)

15 November 2006

Ionic Liquids

AMA 28

Heck Reaction
D PP P (2 eq .)
N Et 3 (1 .2 e q)
P d( OAc )2 ( 2.5 mo l% )

A rX

OBu

[b m im ][B F 4 ], 1 00 C , 1 8 h

Ar

OBu
!

Su bs tra te

Te mp e ra tur e ( C )

Tim e (h ) C o nv er sio n (% )

OB u

Ar
"
!/ "

Y ie ld (% )

Br
10 0

24

100

>9 9 /1

95

80

24

100

>9 9 /1

94

Ph2 P

Br
11 0

36

100

>9 9 /1

94

12 0

36

100

>9 9 /1

90

PPh2
DPPP

NC
Br
M eO 2C
Br
Me

12 0

36

100

>9 9 /1

92

10 0

24

100

>9 9 /1

93

12 0

24

100

>9 9 /1

97

10 0

24

100

>9 9 /1

95

12 0

36

100

>9 9 /1

88

Me N

BF4 -

[bmim][BF4]

O
Br
H
O
Br
F
Br

Br
Me

15 November 2006

Ionic Liquids
Xu, L.; Chen, W.; Ross, J.; Xiao, J. Org. Lett., 2001, 3, 295-297.

AMA 29

Swern Oxidation
Ionic liquid tethered dimethyl sulfoxide can be prepared with no chromatography
and no volatile (read: smelly) organosulfur reagents
Products separated from ionic liquid by phase extraction with ether
Reduced sulfide may be reoxidized and reused for at least 4 recycles with small loss
of activity
Also able to tether TEMPO catalyst
1)

Br

OH
N

!
N

N
TfO -

OH

2 ) Ag OTf, Me C N

M sC l
C s2 C O 3

S
1)

Me C N

H2 N

H 5 IO 6

N H2

M eC N
N

N
TfO -

OMs

2 ) N a OH /H2 O
3 ) M e2 S O 4

98%
N

N
TfO

9 4%
6 s te p s
no ch ro ma to gr ap y

TfO -

- 78 C
O

15 November 2006

(C OC l)2 , NE t 3
C H 2C l 2/M eC N

Ionic Liquids
He, X.; Chan, T. H. Tetrahedron, 2006,62, 3389-3394

OH

AMA 30

Swern Oxidation
H5 IO 6
N

(COCl)2 , NEt3
CH 2Cl2/MeCN

TfO -

O
S

N
TfO -

-78 C
O

OH

Substrate

Product

OH

Yield(%)

O
90
OH

OH

81

88

95

H
OH

86

BnO

87

BnO

O
82

O
Me Me

O
Me Me

Me

Me

90

OH

15 November 2006

Ionic Liquids
He, X.; Chan, T. H. Tetrahedron, 2006,62, 3389-3394

AMA 31

RCM

Simple dissolution of catalyst not effective catalyst soluble in organic solvents

& decomposes

HO

OMe

Br

1 ) N aH , iP rI, D MF 9 0%
2 ) Br2 , H OAc , C H 2 C l2 , 9 8 %
3 ) Li Al H 4, TH F, 95 %

1 ) 1- me thy li mi da zo l e, Ph M e
2 ) H PF 6 , H2 O, 8 7% - 2 step s
3 ) 1, C u Cl , CH 2 C l2 , 78 %

Br
O

Cl
Cl

HO

P Cy 3
Ru

1) B u3 S nC H C H 2, Pd (P Ph 3 )4 , P hM e , 7 5 %
2) N Et 3 , Ms Cl , CH 2 C l2
3) L iB r, TH F, D M F, 7 4 % - 2 s te p s

PF 6 - N

15 November 2006

Ionic Liquids

Audic, N.; Clavier, H.; Mauduit, M.; Guillemin, J-C. J. Am. Chem. Soc., 2003, 125, 9248-9249.

Cl
Cl

P Cy 3
Ru
P Cy 3Ph
1

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Ring Closing Metathesis

R
Cl
Ru
Cl

PF6-

N
N

O
R

[bmim][PF6 ], 60 C

! 5 mol% cat.
! 4h
R

Substrate
Ts
N

PCy3
Ts
N

Product
Ts
N

Ts
N

PCy3

Ts
N

sIMesa

Ts
N

Conversion(%)

>98

>98

>98

>98

>98

>98

97

92

>98

>98

>98

96

93

91

80

>98

>98

>98

>98

>98

>98

95

[bmim][PF6 ]

95
Mes N

EtO 2C CO2 Et

EtO2 C CO 2Et

sIMes (25C)a
O
PCy3

>98

>98

>98

94

78

48

>98

>98

>98

83

PF6 -

33

N Mes

sIMes

biphasic with toluene (25:75, [bmim][PF6] : toluene)

15 November 2006

Ionic Liquids

Audic, N.; Clavier, H.; Mauduit, M.; Guillemin, J-C. J. Am. Chem. Soc., 2003, 125, 9248-9249.

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The Future
Chiral functionalized ionic liquid
Side chain or anion incorporates chirality
Asymmetric induction
Kinetic resolution

Task-specific ionic liquids

Incorporate reagent or catalyst or substrate into
cation or anion
If substrate can carry substrate on several steps,
immobilized in ionic liquid allows for easy
separation/recovery

Supercritical CO2

Used to extract product from ionic liquid phase

without using molecular solvents

15 November 2006

Ionic Liquids

AMA 34

Summary
Ionic liquids viable alternative to molecular
solvents in many reaction types
Ionic liquids allow for potential recovery/reuse
of catalyst (it may be the catalyst itself)
Rate enhancement, ease of product isolation,
recyclability of catalyst ionic liquids could
become widely popular in near future

15 November 2006

Ionic Liquids

AMA 35

References
Properties:
Handy, S. T. Current Organic Chemistry, 2005, 9, 959-988.
Dupont, J.; Spencer, J. Angew. Chem. Int. Ed., 2004, 43,
5296-5297.
Baudequin, C.; Brgeon, D.; Levillain, J.; Guillen, F.;
Plaquevent, J-C.; Gaumont, A-C. Tetrahedron: Asymmetry,
2005, 16, 3921-3945. (Chiral ionic liquids)
Welton, T. Chem. Rev., 1999, 99, 2071-2083.

Reactions:
Sheldon, R. Chem. Commun., 2001, 2399-2407.
Song, C. E. Chem. Commun., 2004, 1033-1043.
Lee, S. Chem. Commun., 2006, 1049-1063. (Functionalized
ionic liquids)
Miao, W.; Chan, T. H. Acc. Chem. Res., ASAP (Ionic liquidsupported synthesis)
Jain, N.; Kumar, A.; Chauhan, S.; Chauhan, S. M. S.
Tetrahedron, 2005, 61, 1015-1060.
15 November 2006

Ionic Liquids

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