Understanding Enolate Chemistry and the Tishchenko...
20
Dan Waddell June 24, 2009 Understanding Enolate Chemistry and the Tishchenko Reaction Under High Speed Ball Milling Conditions
Transcript of Understanding Enolate Chemistry and the Tishchenko...
Dan WaddellJune 24, 2009
Understanding Enolate Chemistry and the Tishchenko
Reaction Under High Speed Ball Milling Conditions
12 Principles of Green Chemistry• Prevention
• Atom Economy
• Less Hazardous Chemical Syntheses
• Designing Safer Chemicals
• Safer Solvents and Auxiliaries
• Design for Energy Efficiency
• Use of Renewable Feed stocks
• Reduce Derivatives
• Catalysis
• Design for Degradation
• Real-time Analysis for Pollution Prevention
• Inherently Safer Chemistry for Accident Prevention
Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and Practice, Oxford University Press: New York, 1998, p.30.
How to Prevent Waste
Non-Solvent Chemical Waste Methanol Toluene1,2-Dichloroethane Ethylene Glycol DichloromethaneXylenes Benzene n-hexaneAcetonitrile Cyclohexane Carbon DisulfideTetrachloroethylene Chloroform Carbon TetrachlorideDimethylformamide 1,4-Dioxane Pyridine
32%68%
Total Waste = 11.5 Billion Pounds
Total Solvent Waste = 3.7 Billion Pounds
EPA Toxic Release Index: 2005
Eliminate Organic Solvents
-Large volume used in industry
-Difficulty containing volatile compounds
- $$$$ Cost $$$$
http://www.epa.gov/triexplorer/chemicalquantity.htm
Why?
Why use solvents anyway?
Aristotle’s Conclusion:“No Coopora nisi Fluida”
“No reaction occurs in the absence of solvent”
Mack LabSPEX mixer/mill
Custom Vials
Path of BallA. Concas et al. / Chemical Engineering Science 61 (2006) 3746 – 3760
Mixer/Mill
My projects
Tishchenko Reaction
Carbon-carbon bond formation– Regio- and Stereoselectivity
Tishchenko Reaction
• Environmentally Friendly
– 100% atom economic
– Use of catalyst• Both reduce chemical
waste
• Industrially Relevant
– Create benzyl benzoate• Flavorings and
Fragrances
– Create ethyl acetate• Common organic solvent
Tishchenko Reaction
History1887: First reported by Claisen using sodium alkoxide1906: Tishchenko used aluminum alkoxides and broadened the scope of the reactions
Tishenko, V., J. Russ. Phys. Chem. Soc. 1906, 3 8 , 355.Claisen, L., Chem. Ber. 1887, 2 0 , 646.
Other catalysts have been applied to increase scope of the Tishchenko reaction
HSBM Tishchenko
Daniel C. Waddell and James Mack, An environmentally benign solvent-free Tishchenko reaction, Green Chem., 2009, 11, 79 – 82.
Aryl Aldehydes Continued
Daniel C. Waddell and James Mack, An environmentally benign solvent-free Tishchenko reaction, Green Chem., 2009, 11, 79 – 82.
Non-Aryl Aldehydes
H
OH
O
O
H
H
O
O
H
O
HPolymer
Formation
Mainly conjugate additon products
Daniel C. Waddell and James Mack, An environmentally benign solvent-free Tishchenko reaction, Green Chem., 2009, 11, 79 – 82.
O
OO
H
H
O
Other Tischenko Considerations
• Magnesium turnings can be used to catalyze the reaction– Magnesium vial under investigation
• Aluminum vial also catalyzes reaction– Create Aluminum Alkoxides (original catalyst
for these reactions)– Use HgCl2 and isopropanol
Second Project:Carbon-carbon bond formation
• Fundamental Organic Transformation
• Enolate Chemistry is arguably the easiest method
Prof. Dr. Burkhard König, Institut für Organische Chemie, Uni Regensburg
Solvent-Free Literature Precedent?
Mortarand
Pestle5 min
NaOH
O
H
O O
+
K. Tanaka and F. Toda, Chem. Rev., 2000, 100, 1025–1074.
Ketone Electrophile 97%
C. L. Raston, J. L. Scott, Green Chem. 2000, 2, 49 – 52.
Probing SelectivityKinetic vs. Thermodynamic Control
• 2-methylcyclohexanone as a model system
HO
H
O–
O–
Thermodynamic enolate
Kinetic enolate
Kinetic vs. Thermodynamic
• Is this regioselectivity possible under HSBM conditions?– Prevailing thought:
• HSBM is an extremely high energy system• All reactions should proceed to the thermodynamic
product
• Test the system– Use KOH as a thermodynamic base– Use LiHMDS as a kinetic base N
SiSi
Li
Selectivity!O
BrO
Br
Br
+ + KOH1/8" ss ball
O
Br24% 5%
Thermodynamic Kinetic
O
Br
Br
+ +1/8" ss ball
HMDS
O
Br
O
Br10% 44%
Br
O
Br8%
Thermodynamic Kinetic
Daniel C. Waddell, Indre Thiel, S. Tyler Marcum and James Mack, Making kinetic and thermodynamic enolates via solvent-free high
speed ball milling, Green Chem., submitted.
Other Base Choices1/8" ss ball
BASE
Br
BrO
+ +1/8" ss ball
BASE
Br
BrO
+ +
O
Br Br
O
Br
O
Br
NaOH 76% 2%
LiOH
CsF/LiOH 9%9%50%
-/- -/- -/-
-/-
BASE
NaH0.6 equiv.
46% 2% -/-
LiHMDS0.9 equiv.
9% 19% -/-Daniel C. Waddell, Indre Thiel, S. Tyler Marcum and James Mack, Making kinetic and thermodynamic enolates via solvent-free high
speed ball milling, Green Chem., submitted.
Conclusions
• HSBM is a viable technique to create a paradigm shift in the way we perform organic reactions
• Tishchenko reaction is successful for a variety of aryl aldehydes
• Stereo- and regio-selectivite enolate chemistry is viable under HSBM conditions
Acknowledgements• Dr. James Mack• Mack Group• Indre Thiel
– Cincinnati REU Program• S. Tyler Marcum• Brandon Smith• NSF Scholars Program• University of Cincinnat
– University Research Council• NSF - 0548150
