Charles A. Eckert

Novel Solvents for
Sustainable Technology

Prof. Charles A. Eckert, Prof. Charles L. Liotta

Georgia Institute of Technology, Atlanta, GA


and Prof. Philip G. Jessop

Queen’s University, Kingston, Ontario

CHEMRAWN
-
XVII and ICCDU
-
IX

GREENHOUSE GASES
–

Mitigation and Utilization,

Kingston, ON, Canada, 11 July, 2007

“
Sustainable”
is not just
hugging a
tree
…

It’s getting everyone to hug a tree

Sustainable Chemical Process

•
Major Cost: Separation and Purification

•
Systems Approach


Modify Reaction to Facilitate Separation

•
Applications:

Chemicals Pharmaceuticals





Microelectronics

Biotechnology

Reactor

Separator

Recycle

Raw

Material

Products

Novel Solvents Using CO
2

•
Supercritical CO
2

•
Gas
-
Expanded Liquids

•
Reversible Acids

•
Reversible Ionic Liquids

Supercritical CO
2

for Phase Transfer Catalysis

•
Reaction of Species of Different Polarity


Not Both Soluble in Most Common Solvents


Involves Reaction Between Phases, i.e. Toluene
-
Water

•
Alternative: PTC


Tetraheptyl Ammonium Bromide


‘Greasy” Counterion
--






Brings CN
-

into Toluene


C
N
K
B
r
B
r
K
C
N


N

C

7

H

15

CN
-

-

C

7

H

15

C

7

H

15

C

7

H

15

+

Phase Transfer Catalysis in SCFs:

Typical Reactions

K
C
N


+
K
C
l


+
C
H
2
C
l
C
H
2
C
N
C
a
t
a
l
y
s
t
C
H
2
C
N
C
a
t
a
l
y
s
t
+


C
H
3
C
H
2
B
r
C
H
C
N
C
H
2
C
H
3
Three
-
Phase PTC System with
Catalyst
-
Rich Surface Phase


Solid Phase



Catalyst Phase

Supercritical

CO
2

Phase


C

H

2

C

l

C

H

2

C

N


KCN


N

+

Benefits of SCFs for PTC

•
Environmentally Friendly

•
Favorable Transport Properties

•
Tunable with Density

•
Tunability with Cosolvents

•
Easy Solvent Removal

•
Catalyst Recycling Opportunities

Liquid

GAS

Liquid



G
as
-
E
x
panded
L
iquids (
GXL
s)

Tunable Organic
-
CO
2

Mixtures

GAS

Liquid

•
Good Organic Solvents
Miscible with CO
2

Add CO
2

•
Solvent properties are
pressure tunable

•
Separation by
Depressurization

•
Solubility is Pressure
Tunable

Properties of GXLs:

Phenanthrene Sol’y in Acetone, 25
°
C

0.0001
0.001
0.01
0.1
1
0
20
40
60
80
Pressure (bar)
mol fraction Phenanthrene
Liquid CO
2

Liquid Acetone

Acid Properties of GXLs

Methanol + Reichardt’s
Dye (Indicator)

CO
2

Same Flask after CO
2

Introduction

In Situ Formation of Acids from CO
2

O
H
3
C
H
O
C
O
C
H
3
O
O
H
O
+
O
H
H
O
C
O
+
H
O
O
H
O
+
O
C
O
H
2
O
2
O
O
H
O
H
O
Water + CO
2

Methanol + CO
2

Hydrogen Peroxide + CO
2


(for oxidation reactions)

β
-
Pinene to
α
-
Terpineol in GXL/MeOH

•
Fragrances, Intermediates

•
Current Process


Aqueous, Acidic


Neutralization, Waste Salt


Limited Solubility of
β
-
Pinene (10
-
15 ppm)

•
Reactants Much More Soluble in Methanol

•
Forms Methylcarbonic Acid


No Need to Add or Neutralize Acid


Reversible Acid Forms In Situ

•
Product Separation Tunable with CO
2

Pressure

•
No Waste Salt

O
H
H
+
O
rganic
A
queous
T
unable
S
olvents
(OATS)

for Homogeneous Catalysis

+ CO
2

-

CO
2

Organic


H
2
O

Catalyst

Vapor

GXL

Vapor

Aqueous

Catalyst

•
Homogeneous Reaction


Organic/Aqueous Solution


Ambient Pressure

•
CO
2

Induces Phase Split


Heterogeneous Separation

•
GXL Poor Solvent for


Ionic Catalysts


Enzymes

•
Decant, Depressurize


Catalyst Recycle


Product Purification

Organic
-
Aqueous Tunable Solvent: OATS

CO
2

Effect on LLE for THF/Water

0
25
50
75
100
125
150
0
50
100
Mass % Organic
Temperature °C
No CO
2
10.3 Bars CO
2
Water
-
THF
-
CO
2

Equilibria

Left: No CO
2


Single Liquid Phase

Water Soluble Dye


Right: 20 Bars CO
2

Two Liquid Phases,
Dye Partitioning > 10
5

Cover Picture,
J.
Phys. Chem. B
, 2004

OATS Reaction: Hydroformylation

•
Water
-
soluble catalyst

•
Minimal Rh loss

•
Industrial Process for Propylene

•
Mass transfer inhibited for larger olefins

•
THF improves solubility

•
TON improved 50
–

100 Fold

•
Isomerization Problems

C
O
,

H
2
,

1
2
0
°
C
,

2
0

b
a
r
H
C
O
R
h
L
3
O
H
H
O
O
c
t
e
n
e

i
s
o
m
e
r
s
P
N
a
O
3
S
N
a
O
3
S
S
O
3
N
a
Hydroformylation

Reaction Rate

0
50
100
150
200
250
300
350
400
TPPTS
Biphasic
TPPTS
Monophasic
TPPMS
Monophasic
Turnover Frequency (hr
-1
)
OATS for Biocatalytic Synthesis and
Purification of Hydrophobic Drugs

•
Enantioselective Biocatalysis


Water Insoluble Substrates


Facile Product Isolation and Catalyst Recycle

•
OATS Mixture


Benign Alternative for Organics


Higher Enantioselectivity


Higher Efficiency


Higher Stability of Enzymes


Facile Purification of Pharmaceuticals

Biocatalytic Synthesis of Chiral Alcohols

H
O
H
N
A
D
H
+
H
N
A
D
+
F
D
H
H
C
O
O
H
C
O
2
O
A
D
H
Enzymes: ADH (alcohol dehydrogenase),



FDH (formate dehydrogenase);



Cofactor: NAD(H)
—

hydrogen transfer agents;



Buffer: 0.1 M ammonia formate, pH


6.5

NADH
-
dependent enzymatic reduction of

less
-
water soluble ketones

Recovery Efficiency of (s)
-
(
-
)
-
sec
-
Phenylethyl Alcohol in OATS

95%
96%
97%
98%
99%
100%
20
30
40
50
60
P
CO2
(bar)
Recovery in organic phase
Acetonitrile/Water (50:50), 40
°
C.
(0.2 mol/L NH
4
HCO
3

buffer, pH 5)

OATS:

Homogeneous Reaction/Heterogeneous Recovery

Products

Product
Purification

Reactants

Aqueous/Enzyme Recycle

Organic Solvent Recycle

CO
2

in

CO
2


out




Homogeneous
Biocatalysis


Product/


Organic

(GXL)

Enzyme/

Aqueous

Best of Both Worlds


Difficult Separation






Product


Contamination


Variation in


Activity or


Selectivity




Catalyst Leaching



off Support



Mass Transfer


Limitations





Facile
Separation

Increased:
-

Selectivity
-

Yields
-

ee’s

Reversible Ionic Liquid

CO
2

(1 atm.) Acts as “Switch”

•
DBU

(1,8
-
diazabicyclo
-
[5.4.0]
-
undec
-
7
-
ene)


N
N
+


R
O
H
N
N
H
R
C
O
3
-
C
O
2
-
C
O
2
Non
-
Polar


Chloroform

Polar (Ionic Liquid)


Dimethylformamide
or Propanoic Acid

Jessop, Heldebrant, Li, Eckert, Liotta,
Nature

2005
,
436
, 1102.

Guanidine Cased ILs

•
Guanidines + MeOH + CO
2



RTILs

•
Reverses Readily


With Inert Gas Sparge, Heat




N
N
N
R
N
N
N
R
H
O
2
C
O
M
e
M
e
O
H
C
O
2
Polarity like

Chloroform


Significantly More Polar
than [bmim][BF4]

Reversible IL as a Solvent

•
S
oluble in DBU and TMBG


Octane, Heptane, Pentane

•
Phase separation upon formation of IL


Negligible Cross
-
contamination

CO
2

Hydrocarbon

TMBG/MeOH

Hydrocarbon


Phase

TMBGH
+
/

N
2

or Heat

MeOCO
2
-


Reaction/Separation in Reversible ILs

1
-

Pentane


2
-
MeOH/CO
2

A + B

Product C

Product C

Heat or N
2

DBU or TMBG

Ionic Liquid

Pentane

REACTION

SEPARATION

REFORMATION

RECYCLE

Novel CO
2
-
Based Solvents to
Couple Reaction and Separation

•
Build Separation Scheme into Reaction

•
Tunable Solvents


Supercritical


Nearcritical


Gas
-
Expanded Liquid

•
“Smart” Solvents

•
Sustainable Processes