Greener Solvents

Dr. Tamer Andrea

Queen’s University
GreenCentre Canada
The Commercialization Gap
Typical stage of university technologies:
• Bench-test proof of utility
• Applications speculative and unproven
• Incomplete material characterization
• Grams of sample
• Manufacturing feasibility not studied

What Industry wants:

• Demonstrated scale-up
• Optimization
• Field-test proof of utility
• Kilograms of sample
 Process for Technology Disclosures
GCC GCC
Option exclusive
license

Stage 2: Stage 3:
Stage 1:
Technology Technology
Quick Screening
Assessment Development

Output: technology
returned without
assessment
$ Output:
licensable
technology;
$
Assessment indicates need 75/25 split
for PoP funding
Output: analysis of
commercialization potential
Green Solvents
Dr. Philip Jessop
Queen’s University
GOALS OF GREEN CHEMISTRY: REDUCE SOLVENT USE

Industry segment Product tonnage E factor

Mass of waste
“E” factor = Bulk chemicals 104 - 106 <1 - 5
Mass of product
Fine chemicals 103 - 104 5 - 50

Pharmaceuticals 10 - 103 25 - over 100

R. Sheldon, CHEMTECH 1994, 38.

Mass utilization in fine chemical production

Other
10-20%

Solvent 80-90%

http://www.caraet.com/Waste_solvent.htm
PROBLEMS WITH CURRENTLY USED SOLVENTS

In the US in the early 1990’s:

• solvent production was 26 million tons p.a.
• of tracked chemicals, many of the top chemicals released or disposed of were solvents
(MeOH, toluene, xylene, CS2, MEK, CH2Cl2)

Organic solvent hazards

• flammable (almost all except chlorinated solvents)

• carcinogenic (chlorinated solvents and aromatics)

• high vapour pressure (i.e. inhalation route)

• narcotic (ether, chloroform)

• toxic (MeOH, CS2)

• mutagens/teratogens (toluene)

• peroxides (ethers)

• smog formation
OUTLINE

1. Reducing the Impact of Solvents

2. Solvent Properties

3. Greener Conventional Solvents

4. Unconventional Solvents

5. Conclusions
DECREASING THE IMPACT OF SOLVENTS

1. Reduce the volume of solvent

• use higher concentrations
• use solvent for more than one step

2. Make the solvents greener

• carefully chosen conventional solvents
• new green solvents
Murphy’s Law of Solvents

“The best solvent for any

process step is bad for the
subsequent step.”
AN IMAGINARY PROCESS

Solving Murphy’s Law of Solvents

1. A Compromise Solvent

2. A Switchable Solvent
CAREFUL SELECTION OF A TRADITIONAL SOLVENT

http://www.rx-pharmacy.cc/product_info.php?products_id=169
SWITCHABLE-POLARITY SOLVENT

CO2

N2 or Ar

Nature (2005) 436, 1102

Ind Eng Chem Res (2008) 47, 539
APPLICATION TO POLYSTYRENE SYNTHESIS

75 ˚C CO2
6h

1.0 mL styrene
4.5 mL DBU/PrOH filter or centrifuge
45 mg initiator

N2 +

Mn = 412,000
PDI = 1.57
DECREASING THE IMPACT OF SOLVENTS

1. Reduce the volume of solvent

• use higher concentrations
• use solvent for more than one step

2. Make the solvents greener

• carefully chosen conventional solvents
• unconventional solvents
OUTLINE

1. Reducing the Impact of Solvents

2. Solvent Properties

3. Greener Conventional Solvents

4. Unconventional Solvents

5. Conclusions
PROPERTIES OF CONCERN

For green-ness
boiling point / energy to distill
flash point
energy to distill
cumulative energy demand
the 10 factors

For utility
polarity
basicity / hydrogen-bond accepting ability
acidity / hydrogen-bond donating ability
viscosity
THE TOOLBOX ANALOGY
KAMLET-TAFT SOLVATOCHROMIC PARAMETERS

cyclohexane
KAMLET-TAFT SOLVATOCHROMIC PARAMETERS

protic
solvents

α (acidity)

aprotic
solvents

β (basicity)
π* (polarity/polarizability)
KAMLET-TAFT SOLVATOCHROMIC PARAMETERS

1.2
water

protic
solvents

formamide
tBuOH
α (acidity)

CHCl3

aprotic
solvents
HMPA
1.1
toluene
NEt3
1.1

β (basicity)
π* (polarity/polarizability)
cyclohexane
 SURVEY OF SOLVENTS (APROTIC)

1.1
HMPA
High basicity

1
0.9 tetramethyl-
urea
0.8 OP(OEt)3
DMA NMP
DMSO
NEt3
0.7 Me2py DMF
4-Mepy quinoline
NBu3 BzNMe2 pyridine
0.6 THF
β

MEK
0.5 acetone butyrolactone
Et2O EtOAc
Pr2O EtO2CPhpropylene PhCN
EtO2CEt MeOAc
0.4 MeOC2H4OMe MeO2CH carbonate PhNO2
Low basicity

dioxane sulfolane
anisole MeCN
0.3 EtO2CCl3
0.2 p-xylene toluene
cyclohexane, benzene
PhCl PhBr
0.1 hexane, CCl4 & MeNO2
heptane Cl2C=CCl2 Cl2C=CClH CHCl3 CH2Cl2
0 ClC2H4Cl
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 1.1
Low polarity π* High polarity

Jessop, Green Chem (2012) 14, 1245

 SURVEY OF SOLVENTS (PROTIC)

1.1
High basicity

tBuOH
1
iPrOH
0.9 1-propanol
butanol
hexanol
0.8 octanol
ethanol

0.7
methanol
0.6
PhCH2OH
β

ethylene glycerol
0.5 hexanoic glycol
acid acetic acid formamide
0.4
Low basicity

0.3 phenol

0.2 water

0.1
CF3CO2H (CF3)2CHOH CF3CH2OH
0
0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 1.1
Low polarity π* High polarity

Jessop, Green Chem (2012) 14, 1245

OUTLINE

1. Reducing the Impact of Solvents

2. Solvent Properties

3. Greener Conventional Solvents

4. Unconventional Solvents

5. Conclusions
PFIZER SOLVENT SELECTION GUIDE
WHICH SOLVENT IS GREENER?

solvent #1 solvent #2

General Comparison
• solvent impact
• solvent impact including manufacture
• energy to manufacture / cumulative energy demand

Application-Specific Comparision
• ISO LCA
ENVIRONMENTAL AND HEALTH RISKS

Alcohols Acids Dioxane

Acetate esters Acetonitrile Formaldehyde

Capello et al., Green Chem (2007) 9, 927

ENERGY REQUIREMENT FOR MANUFACTURE

300

250

200
MJ/kg

150

100

50

0
Ethanol Hexane Acetone Toluene DMF EtOAc THF
Capello et al., Green Chem (2007) 9, 927
ENERGY REQUIREMENTS FOR A SOLVENT

How is hexane made? How is DMF made?

distillation
oil hexane
WHICH SOLVENT IS GREENER?

solvent #1 solvent #2

General Comparison
• solvent impact
• solvent impact including manufacture
• energy to manufacture / cumulative energy demand

Application-Specific Comparision
Why would this give
• ISO LCA
a different result?
PROPOSED NEW GREEN ORGANIC SOLVENTS

g-valerolactone
ethyl lactate

low toxicity, biodegradable, renewable low toxicity, biodegradable, renewable

Aparicio, Green Chem. (2009) 11, 65 Horvath, Green Chem., 2008, 10, 238

2-methyltetrahydrofuran cyclopentylmethylether

renewable doesn’t form peroxides, low solubility in water

Aycock, Org. Process Res. Dev. 2007, 11, 156 Watanabe, Org. Process Res. Dev. 2007, 11, 251
 GREEN SOLVENTS (APROTIC)

1.1
High basicity

1
0.9
0.8
0.7 PEG
PPG
0.6 2-MeTHF γ-valerolactone
β

MEK
0.5 acetone
EtOAc
(EtO)2CO propylene
iPrOAc
0.4 carbonate
Low basicity

0.3
0.2
0.1
heptane
0
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 1.1
Low polarity π* High polarity

Jessop, Green Chem (2012) 14, 1245

 GREEN SOLVENTS (PROTIC)

1.1
High basicity

tBuOH
1
iPrOH
0.9 1-propanol
butanol

0.8 ethanol

0.7
methanol
0.6 ethyl lactate
β

glycerol
0.5
0.4
Low basicity

0.3
0.2 water

0.1
0
0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 1.1
Low polarity π* High polarity

Jessop, Green Chem (2012) 14, 1245

OUTLINE

1. Reducing the Impact of Solvents

2. Solvent Properties

3. Greener Conventional Solvents

4. Unconventional Solvents

5. Conclusions
UNCONVENTIONAL SOLVENTS

water liquid polymer switchable solvent

supercritical CO2 ionic liquid CO2-expanded liquid

IN WATER

Why not water?

http://students.washington.edu/~haoli/photo_gallery/archives/olympic/

Li, 1995
 SWITCHABLE WATER

CO2
water & water &
B -CO2 [BHn][HCO3]n

• low ionic strength • high ionic strength

• low osmotic pressure • high osmotic pressure
• good solvent for polar organics • poor solvent for polar organics

product
water, B, & product
CO2
product water, B, &
water &
filter product
[BHn][HCO3]n

-CO2

Mercer, Jessop, et al. ChemSusChem (2010) 3, 467

Mercer, Jessop, et al. Green Chem (2012) 14, 832
IONIC LIQUIDS

NaCl, mp 801 ˚C

NaBF4, mp 384 ˚C

[PiBu3Me]O3SC6H4Me, mp < RT

Nonvolatile
Nonflammable
Doesn’t create smog
No inhalation hazards
 BY GENERAL COMPARISON, ARE IONIC LIQUIDS GREEN?

Zhang, Env. Sci. Tech. (2008) 42, 1724

Jessop, Green Chem (2011) 13, 1391

 CHEMICAL STEPS IN SOLVENT SYNTHESIS

Jessop, Green Chem (2011) 13, 1391

 CHEMICAL STEPS IN SOLVENT SYNTHESIS

Jessop, Green Chem (2011) 13, 1391

LIQUID POLYMERS
LIQUID POLYMERS

liquid polymers ionic liquids

Nile Red scale

Heldebrant, Jessop et al. Green Chem (2006)

SOME ORGANIC SOLVENTS ARE VOLATILE

Volatile Solvents Nonvolatile Solvents

• flammability • no flammability
• high insurance costs • low insurance costs
• vapour losses • no vapour losses
• smog formation • no smog formation
• inhalation hazards • no inhalation hazards
- toxic,
- narcotic,
- mutagenic,
- carcinogenic
SWITCHABLE-HYDROPHILICITY SOLVENTS

Green Chem (2010) 12, 809

Green Chem (2011) 13, 619
A REAL WORLD PROBLEM

hexane emissions to air in Canada (NPRI, 2007)

extract
with
solvent distill

Green Chem (2010) 12, 809

 SOY EXTRACTION WITHOUT DISTILLATION

extract
with H2O
solvent CO2

-CO2

Green Chem (2010) 12, 809

Green Chem (2011) 13, 619
[

51
USING A SWITCHABLE-HYDROPHILICITY SOLVENT

Add water
& CO2
extract

oil sands

- CO2

52
OIL SANDS

53
OUTLINE

1. Reducing the Impact of Solvents

2. Solvent Properties

3. Greener Conventional Solvents

4. Unconventional Solvents
• Ionic Liquids
• Liquid Polymers
• Switchable Solvents
• Gas-Expanded Liquids
• Supercritical Fluids
5. Conclusions
EXPANSION OF LIQUIDS BY CO2

CO2-expanded NEt3 (Jessop, 1996)

Volumetric expansion of aprotic solvents by CO2
at 40˚C (Kordikowski, 1995)
Characteristics:
• tunable polarity
• tunable solvent properties
• lowered melting point
• improved mass transfer rates
• improved solubility of reagent gases
EFFECT OF SOLVENT CHOICE

Expansion with CO2 increases in the order:

water < ionic liquid liquid polymer < protic polar < aprotic polar < nonpolar

Class Examples Volumetric Properties that Properties that

change change don’t change

I Water Very small Acidity Most

Glycerol

II Hexane Very large All None

Methanol
DMF

III Ionic liquids Moderate Viscosity Polarity

Liquid polymers Phase behaviour
Crude oil

review paper: Jessop & Subramaniam, Chem. Rev. (2007) 107, 2666
VISCOSITY
1400

1200

1000

Viscosity, cp
800

600

400

200
Crude oil
0
0 20 40 60 80 100 120 140 160
P, bar

Viscosity of CO2-expanded crude oil at 49 ˚C

Simon & Graue, J. Petrol. Technol. (1965) 102.
CO2 CAN TRIGGER INSOLUBILITY AND IMMISCIBILITY

Polar solids are precipitated from solution when the solvent is expanded with CO2

CO2

Some miscible liquids become immiscible when expanded with CO2

CO2 Solvent A Solvent B P, bar

pressure
water methanol 80
water 1-propanol 68
water acetic acid 75
water acetone 26
water THF <10
water 1,4-dioxane <28
water MeCN <19
OUTLINE

1. Reducing the Impact of Solvents

2. Solvent Properties

3. Greener Conventional Solvents

4. Unconventional Solvents
• Ionic Liquids
• Liquid Polymers
• Switchable Solvents
• Gas-Expanded Liquids
• Supercritical Fluids
5. Conclusions
SUPERCRITICAL CO2
SOLUBILIZING POWER DEPENDS ON DENSITY

CO2

Fe3(CO)12
 CO2 AS A SOLVENT

DuPont fluoropolymer plant, N.C

Natex CO2 decaffeination plant

CO2 dry cleaning

Prep SFC (Novasep)

http://www.natex.at/album/index.htm
http://www.metropolitanmachinery.com/sail_star.htm
http://www.pharmaceutical-technology.com/contractors/purification/novasep/novasep3.html
scCO2 AS A SOLVENT

ADVANTAGES DISADVANTAGES

Safety Nonflammable Pressure

Nontoxic
In-situ fire/explosion suppression

Economics Free Pressure

Environment Recycled material

No smog, ozone contribution
Naturally occurring

Process benefits Rapid mass transfer Pressure

High solubility of reagent gases Low solubility of some reagents
Controllable solubilizing power
Easy to separate
OVERVIEW OF UNCONVENTIONAL GREEN SOLVENTS
ionic liquids

switchable
polarity
solvent

ethanol

switchable
cxl MeOH hydrophilicity
solvent

cxl acetone

water
scCO2
SURVEY

If the adoption of greener solvents over the next 20-30 years will reduce
environmental damage from human activities, then the adoption of what class of
solvents will be responsible for the greatest reduction in environmental damage?

• Bioderived solvents (glycerol, 2-methylTHF, valerolactone, etc.)

• CO2 (liquid, supercritical, expanded liquid)
• Conventional organic solvents (carefully selected)
• Ionic liquids
• Switchable solvents
• Solvent-free conditions
• Water (including liquid, superheated, supercritical, on-water)
SURVEY

survey results solvents described in related papers in

Green Chemistry in 2010
WHAT DO WE CHOOSE TO STUDY?
CONCLUSIONS

No solvent is perfectly green.

The nonconventional solvents are more exciting, but it’s

the conventional ones that are greening the industry.

We’re making progress populating the map with green

solvents.

Is it really green? Consider the solvent’s synthesis and

its effect on the entire process.
 CATIONS AND ANIONS

hmim
bmim
emim
hydrophobic hydrophilic

noncoordinating coordinating
GREEN SOLVENTS

1.1
High basicity

tBuOH
1
iPrOH

0.9 PrOH
BuOH
0.8 EtOH
[bmim]O3SOMe4

0.7
MeOH
0.6 MeTHF (est.)
β

MEK
γ-VL (est.)
0.5 MTBE, CypOMe (est.)
EtOAc
acetone aprotic
0.4 iPrOAc protic
[bmim]BF4
Low basicity

0.3 [bmim]NTf2

0.2 Water (150 ˚C)

water
Water (275 ˚C)

0.1
heptane
0
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 1.1
π*
Low polarity High polarity
DISSOLVING CELLULOSE

Solvents known to dissolve cellulose:

Strong alkali & CS2
Cellosolve (EtOCH2CH2OH)
ZnCl2 solution
DMA / LiCl

Graenacher, US Pat. Rogers, JACS (2002)

1943176, 1934 124, 4974

Uses of IL cellulose solutions

• separation from lignin
• prep of cellulose for conversion to EtOH
• derivatization of cellulose

Review: Green Chem., 2006, 8, (4), 325-327

ELECTROCHEMISTRY AND ELECTRODEPOSITION

MCl3 + 3e-

M + 3Cl-

Trulove & Mantz, in Ionic Liquids in Synthesis