Explorations With Deep Eutectic Solvents For Chemical Extractions

Douglas E. Raynie

Department of Chemistry and Biochemistry South Dakota State University douglas.raynie@sdstate.edu

Green Chemistry

Supercritical Fluid

Technology

Analytical Separations Bioprocessing

Chemical Problem Solving

Environmental Analysis

Fundamental Studies

DIFFUSION COEFFICIENT SUMMARY

DECREASING THE IMPACT OF SOLVENTS 1.Reduce the volume of solvent

use higher concentra/ons use solvent for more than one step

2. Make the solvents greener

carefully chosen conven/onal solvents new green solvents

GREEN SOLVENTS

We know guidelines such as like dissolves like, but when it comes to green solvents, how will we

recognize one when we see it?

General Guidelines for PredicHng the Toxicity of Solvents As the number of alipha/c carbons increases, toxicity increases up to about eight carbons. Including subs/tu/ons, toxicity increases as molecular weight increases up to eight carbons. As the number of carbon-carbon double bonds increases, toxicity increases. As the degree of halogena/ons increases, toxicity increases. Brominated compounds are more toxic than chlorinated, which are more toxicity than uorinated. These same general statements are true for alipha/c subs/tu/on on aroma/c compounds. Subs/tu/on of aroma/cs increases toxicity. Subs/tu/on on phenols para- or ortho-, para- to the hydroxyl are more toxic.

PROPERTIES OF CONCERN For greenness boiling point/energy to dis/ll ash point cumula/ve energy demand For uHlity polarity basicity/hydrogen-bond accep/ng ability acidity/hydrogen-bond dona/ng ability viscosity

C. Capello, U. Fischer, and K. Hungerbuhler, Green Chem., 9, 927-934 (2007).

WHAT IS A GREEN SOLVENT?

GSK SOLVENT SELECTION GUIDE

C. Jimenez-Gonzalez, A. D. Curzons, D. J. Constable, and V. L. Cunningham, J. Clean Technol. Environ. Policy, 7, 42-50 (2005).

PFIZER MEDICINAL CHEMISTRY SOLVENT SELECTION GUIDE

Preferred Usable Undesirable

Water Cyclohexane Pentane Acetone Toluene Hexane(s)

Ethanol Methylcyclohexane Di-isopropyl ether 2-Propanol TBME Diethyl ether

1-Propanol Isooctane Dichloromethane Heptane Acetonitrile Dichloroethane

Ethyl acetate 2-Me THF Chloroform Isopropyl acetate THF NMP Methanol Xylenes DMF

MEK DMSO Pyridine 1-Butanol Acetic acid DMAc

t-Butanol Ethylene glycol Dioxane Dimethoxyethane

PFIZER SOLVENT REPLACEMENT TABLE Red Solvents Alternative

Pentane Heptane Hexane(s) Heptane Di-isopropyl ether or ether 2-MeTHF or t-Butyl methyl ether Dioxane or dimethoxyethane 2-MeTHF or t-Butyl methyl ether Chloroform, dichloroethane or carbon tetrachloride

DCM

DMF, NMP or DMAc Acetonitrile Pyridine Et3N (if pyridine used as base) DCM (extractions) EtOAc, MTBE, toluene, 2-MeTHF DCM (chromatography) EtOAc/Heptanes Benzene Toluene

Deep Eutectic Solvents (DES)

Diagrammatic representation of how HBD interacts with a QAS

Eutectic mixtures of quaternary ammonium salts (QAS) and hydrogen bond donors (HBD)

Bulky cations and smaller anions which are bound to a HBD

Abbott, A. P.; Boothby, D et al.; J. Am. Chem. Soc., 2004, 126 (29), 9142-9147.

Choline chloride-Urea (1:2) Choline chloride melts at

302C and urea melts at 133C Molar ratio of choline chloride

to urea is 1:2 The eutectic mixture melts at

12C The depression in freezing

point is 178C

Andrew P. Abbott.; Glen Capper et al.; Chem. Eur. J., 2004, 10, 3769-3774

Choline chloride-Urea

Synthesis General formula

(R1R2R3R4N+) (X-) (R5) (YH) A B C D 106 combinations Not possible to study all the combinations QAS: HBD: Choline chloride Acetylcholine chloride Urea Glycerol

N+

HO

Cl- N+

O

O

Cl-H2N

O

NH2

OH

HO

OH

Andrew P. Abbott.; Glen Capper et al.; Chem. Eur. J., 2004, 10, 3769-3774

Synthesis 16 different combinations of DES were synthesized by

changing the QAS, HBD, and their composition Binary:

QAS+HBD (4 combinations)

Ternary:

QAS+HBD+HBD (6 combinations)

QAS+QAS+HBD (6 combinations)

Components Composition Choline chloride: Urea 1:2

Choline chloride: Glycerol 1:2

Acetyl choline chloride: Urea 1:2

Acetyl choline chloride: Glycerol 1:2

Choline chloride: Urea: Glycerol 1:1:1

Choline chloride: Urea: Glycerol 2:3:1

Choline chloride: Urea: Glycerol 2:1:3

Acetyl choline chloride: Urea: Glycerol 1:1:1

Acetyl choline chloride: Urea: Glycerol 2:3:1

Acetyl choline chloride: Urea: Glycerol 2:1:3

Choline chloride: Acetyl choline chloride: Urea 1:1:4

Choline chloride: Acetyl choline chloride: Urea 1:2:6

Choline chloride: Acetyl choline chloride: Urea 2:1:6

Choline chloride: Acetyl choline chloride: Glycerol 1:1:4

Choline chloride: Acetyl choline chloride: Glycerol 1:2:6

Choline chloride: Acetyl choline chloride: Glycerol 2:1:6

QAS+HBD (4combinations)

QAS+HBD+HBD (6 combinations)

QAS+QAS+HBD (6 combinations)

Phase Properties

Tc range from -37C to -15C Tm range from 12C to 25C Tc and Tm values of DES were far less than the

corresponding QAS and HBD used in their synthesis Tdecomp (10%) range from 186C to 208C

Viscosity Range from 5.4294 x 10-1 Pa.sec to 0.9243 x 10-2 Pa.sec As the choline chloride concentration increased, viscosity

decreased Viscosity studied as a function of temperature from 25C

-150C, with increasing temperature viscosity decreased

Range from 1.1684 g/mL to 1.264 g/mL As the glycerol concentration increased, density increased

Density

pH

Range from 10.44 to 5.42 As the acetylcholine chloride concentration increased, pH

decreased As the urea concentration increased, pH increased

Kow Range from 0.061 to 0.141 As the glycerol concentration increased, Kow increased

RefracHve Index

Ranges from 1.43-1.51 Relates to polarity (water is 1.33)

Choline Chloride

Urea

Glycerol

1:2 Choline Chloride: Urea

1:2 Choline Chloride: Glycerol

1:1:1 Choline Chloride:Urea: Glycerol

Water S S S S S S

Acetone IS IS IS IS IS IS

Acetonitrile IS IS IS IS IS IS

Methanol S S S S S S

Ethanol S S S S S S

Isopropanol IS IS S IS S IS

Dichloromethane IS SS IS IS IS IS

Chloroform SS SS IS IS IS IS

DMSO SS S S S S S

Pentane IS IS IS IS IS IS

Hexane IA IS IS IS IS IS

Toluene IS IS IS IS IS S

Miscibility with Common Solvents

S= soluble SS = slightly soluble IS = insoluble

DES soluble with polar solvents

*

Cyclohexane 0 0 0

Benzene 0 0.1 0.59

Acetonitrile 0.19 0.31 0.75

Water 1.17 0.47 1.09

1:2 Choline Chloride:Urea

0.734 0.632 0.987

1:2 Choline Chloride:Glycerol

0.927 0.642 0.979

1:1:1 Choline Chloride:Urea:Glycerol

0.917 0.765 0.985

= acidity, H-bond dona/ng ability = basicity, H-bond accep/ng ability * = polarity and polarizability

Kamlet-TaQ Solvatochromic Parameters

DES

DES

DES

DES

Dissolution of Sugars

Glucose Sucrose Dextrose Xylose

1:2 Choline chloride: Urea

Soluble Soluble Soluble Soluble

1:2 Choline chloride: Glycerol

Soluble Soluble Soluble Soluble

1:2 Acetyl choline chloride: Urea

Soluble Soluble Soluble Soluble

1:2 Acetyl choline chloride: Glycerol

Soluble Soluble Soluble Soluble

Naturally Occurring DES 1:2, 1:3 Citric Acid:Choline Chloride 1:1, 1:2, 1:3 Malic Acid:Choline Chloride 1:1, 1:2, 1:3 Maleic Acid:Choline Chloride 1:1 Aconi/c Acid:Choline Chloride 1:1:1 Glucose:Choline Chloride:Water 1:1:1 Fructose:Choline Chloride:Water 1:1:1 Sucrose:Choline Chloride:Water 1:1, 1:2, 1:3 Citric Acid:Proline 1:1 Malic Acid:Glucose 1:1 Malic Acid:Fructose 1:1 Malic Acid:Sucrose 2:2 Citric Acid:Glucose 2:1 Citric Acid:Trehalose 1:1 Citric Acid:Sucrose

4:1 Maleic Acid:Glucose 1:1 Maleic Acid:Sucrose 1:1 Glucose:Fructose 1:1 Fructose:Sucrose 1:1 Glucose:Sucrose 1:1:1 Sucrose:Glucose:Fructose

Plant Physiology 156: 1701-1705 (2011).

Analy.cal Chemistry 85: 6272-6278 (2013).

CONCLUSIONS

Deep eutec/c solvents comprise a class of novel, green solvents suitable for separa/ons and other chemical processes.