bringing new and green chemistry into undergraduate ... 2yc3 2011.pdf · bringing new and green...
TRANSCRIPT
Bringing New and Green Chemistryinto Undergraduate Laboratories
David A. Vosburg(and many student coworkers)
Department of ChemistryHarvey Mudd College
Why Go Green?
• minimize toxicity, hazards, and/or waste
• reduce dependence on fume hoods
• modernize with new and exciting chemistry
• innovate, merge with research goals
• contribute to chemical education
• create life-long student advocates
Green Ketone Reduction with Carrots
Ravía, S.; Gamenara, D.; Schapiro, V.; Bellomo, A.; Adum, J.; Seoane, G.; Gonzalez, D. J. Chem. Educ. 2006, 83, 1049.
harmless reagent and solvent, no heating
monitor by thin-layer chromatography (TLC)
extraction, Pasteur pipet column
1H NMR, optical rotation
O O carrot bits
H2O, rt
O OH
Green, Solventless Diels-Alder Reaction
McKenzie, L.C.; Huffman, L.M.; Hutchison, J.E.; Rogers, C.E.; Goodwin, T.E. J. Chem. Educ. 2009, 86, 488.
O
O
O
neat, rt+
OH
?
Green, Solventless Diels-Alder Reaction
McKenzie, L.C.; Huffman, L.M.; Hutchison, J.E.; Rogers, C.E.; Goodwin, T.E. J. Chem. Educ. 2009, 86, 488.
fast, no solvent, no heating, no purification
compare to 110 °C in toluene
melting point, IR spectroscopy
1H and 1H-1H COSY NMR
O
O
O
neat, rt+
OHO
CO2H
O
Green, Organocatalytic Synthesis of Warfarin
Kim, H.; Yen, C.; Preston, P.; Chin, J. Org. Lett. 2006, 8, 5239.Wong, T.C.; Sultana, C.M.; Vosburg, D.A. J. Chem. Educ. 2010, 87, 194.
Terence WongCamille Sultana
+
no heating, no stirring
water/acetone recrystallization
high stereoselectivity
melting point, 1H NMR, optical rotation
O
O
O
OH
O O
OH O
warfarin(anticoagulant)
NH2H2N
AcOH, THFrt, 1 week
(5 mol%)
Green, Enzymatic Synthesis of Divanillin
Rachel NishimuraChiara Giammanco
Russell, W.R.; Scobbie, L.; Chesson, A. Bioorg. Med. Chem. 2005, 13, 2537.Nishimura, R.T.; Giammanco, C.H.; Vosburg, D.A. J. Chem. Educ. 2010, 87, 526.
horseradishperoxidase
dilute vinegardilute H2O2
clean, easy reaction
simple purification
no toxic waste
solubility, melting point, NMR
divanillin(flavor enhancer)
H3CO
HO
H
O
vanillin
H3CO
HO
H
O
OH
OCH3
H
O
+ H2O
Flavor Properties of Divanillin
Gatfield, I.; Reiss, I.; Krammer, G.; Schmidt, C.O.; Kindel, G.; Bertram, H.-J. Perfum. Flavor. 2006, 31, 18.
Divanillin and Diapocynin
divanillin(flavor enhancer)
H3CO
HO
H
O
vanillin
H3CO
HO
H
O
OH
OCH3H
O
diapocynin(antioxidant)
H3CO
HO
O
apocynin
H3CO
HO
O
OH
OCH3
O
Green Synthesis of Citronellal
Anna Cunningham, Haley Ham
practicalenantioselective
catalyst?
expensive,
tedious,
or not stereoselective
citral(lemongrass oil)
O
H
citronellal(citronella oil)
O
H
Green Syntheses of Natural Perfumes
Cunningham, A.D.; Ham, E.Y.; Vosburg, D.A. J. Chem. Educ. 2011, 88, 322. Anna Cunningham, Haley Ham
reducealkene
simple, green,
biomimetic,
and chemoselective
citral(lemongrass oil)
O
H
citronellal(citronella oil)
O
H
geraniol(geranium oil)
OH
epoxycitral(mite pheromone)
O
H
O
reducealdehyde
oxidizealkene
Green Syntheses of Natural Perfumes
Cunningham, A.D.; Ham, E.Y.; Vosburg, D.A. J. Chem. Educ. 2011, 88, 322. Anna Cunningham, Haley Ham
smells wonderful (citrus, rose)
purify by simple extraction
detect by smell, TLC, GC/GC-MS, NMR, IR
citral(lemongrass oil)
O
H
natural perfumes
green, chemoselective,biomimetic reagents
Liquid CO2 Extraction of Limonene from Oranges
McKenzie, L.C.; Thompson, J.E.; Sullivan, R.; Hutchison, J.E. Green Chem. 2004, 6, 355. GCEW 2010
visually impressive, nice smell
no hazardous waste, no purification
optical rotation, GC/GC-MS
liquid CO2extraction
(+)-limonene
Liquid CO2 Extraction of Limonene from Oranges
McKenzie, L.C.; Thompson, J.E.; Sullivan, R.; Hutchison, J.E. Green Chem. 2004, 6, 355. GCEW 2010
Green Bromination of Stilbene
Doxsee, K.M.; Hutchison, J.E. Green Organic Chemistry: Strategies, Tools, and Laboratory Experiments, Brooks/Cole, 2004, 125. GCEW 2010
brief reflux, color change
avoids use of Br2 and CH2Cl2
melting point, GC/GC-MS
trans-stilbene
HBr, H2O2
ethanol
Br
Br
Davanone
• natural product from Indian sageArtemisia pallens
• antifungal and antispasmodic
• davana oil is used in perfume, as askin ointment, and in folk medicine
Artemisia pallens
OOH
davanone
Components of Davana Oil
Misra, L.N.; Chandra, A.; Thakur, R.S. Phytochemistry 1991, 30, 549.
OO
H
davanone
OO
H
artemone
OO
H
isodavanone
OO
H
nordavanone
O
OH
OH
davana acid
OO
H
trans-davanone
OO
H
cis-hydroxydavanone
OH
O
OEt
OH
davana acid ethyl ester
OO
H
trans-hydroxydavanone
OH
38% of davana oil by mass 5% 3%
3% 2% 1.5%
1.5% 2.5% 0.7%
Biological Activity of Davanone
Antispasmodic: Perfumi, M.; Paparelli, F.; Cingolani, M.L. J. Essent. Oil Res. 1995, 7, 387.Antifungal: Vajs, V.; et al. J. Serb. Chem. Soc. 2004, 69, 969.
• Antispasmodic0.2 µM in guinea pig small intestines
• Antifungal100 µM vs. ten fungi
OO
H
cis-hydroxydavanone
OH
N
N
bifonazole
25 µM 32 µM
Our Green, Seven-step Synthesis
Morrison, K.C.; Litz, J.P.; Scherpelz, K.P.; Dossa, P.D.; Vosburg, D.A. Org. Lett. 2009, 11, 2217.
OAc OAc
OH
OAc
OHO
SAE
83%
OAc
OO
H
OH O
OEt
OAc N
S
Ph
Cl
EtOHi-Pr2NEt
5:1 anti/syn 83%
O
OEt
OH
SO3•pyrDMSO
O
NO
OH
OO
H
(+)-davanone
ClMg
HNO
i-PrMgCl
96%
2.5:1 cis/trans
Pd2dba3
87%
C3-(S)-TunePhos
90% 62%
SeO2
72%
(31% pure anti,cisfrom aldehyde)
Green, 4-Step Route to (+)-Artemone
Eric NacsaJonathan Litz
Jeep SrisuknimitMary Van Vleet
OO
H
(–)-linalool
artemone
OH
H
OOHSeO2
t-BuOOH
BrIn
OHO
H
OO
H
H
75% anti,cis
microwave120 °C, 20 min
NH OTMS
PhPh
O
I
O
OAcOAc
AcO
25 °C
25 °C
25 °C
Natural Compounds Synthesized
OO
H
davanone
OO
H
artemone
OO
H
isodavanone
OO
H
nordavanone
O
OH
OH
davana acid
OO
H
trans-davanone
OO
H
cis-hydroxydavanone
OH
O
OEt
OH
davana acid ethyl ester
OO
H
trans-hydroxydavanone
OH
Kanny WanEric Nacsa
Jonathan LitzKaren Morrison
Jeep SrisuknimitMary Van Vleet
Outcomes
• reduced toxicity, hazards, waste, and dependence on fume hoods
• students get excited about green chemistry
• colleague support and adoption
• inspires innovation in research projects
• several student-authored posters and publications
• adopting labs in US, Europe, Asia, South America
Recommended Green Resources
• ACS Green Chemistry Institute (ACS GCI)
• Green Chemistry Education Network (GCEdNet)
• Green Chemistry in Education Workshop (GCEW)
• Greener Education Materials for Chemists (GEMs)
• greenchem.uoregon.edu
Acknowledgements
FundingHarvey Mudd Chemistry DepartmentCamille & Henry Dreyfus Foundation
Beckman Scholars FoundationHoward Hughes Medical Institute
American Chemical Society Petroleum Research FundResearch Corporation for Science Advancement
National Science Foundation Research Experiences for UndergraduatesMerck-AAAS Summer Undergraduate Research Program
Pfizer Summer Undergraduate Research Fellowships (SURF)Division of Organic Chemistry SURF
Rose Hills FoundationChristian Scholars Foundation
Pomona Chemistry Department
Green PedagogyRachel Nishimura ’09Terence Wong 09Andrew Chung ’10Helen Fitzmaurice ’10Chiara Giammanco ’10Camille Sultana ’10Athena Anderson ’11Anna Cunningham ’11Haley Ham ’12Jeep Srisuknimit ’12Cory Evans-Klock ’13Bryan Visser ’13Katherine Maloney
DavanonePaul Dossa ’06Kathryn Poindexter ’07Karen Brown ’08Jonathan Litz ’09Ryan Pakula ’09Eric Nacsa ’10Kanny Wan ’11Jeep Srisuknimit ’12Mary Van Vleet ’12Katherine Maloney
12 Principles of Green Chemistry
1. Prevent waste2. Atom economy3. Less hazardous syntheses4. Design safer chemicals5. Safer solvents and auxiliaries6. Energy efficiency7. Renewable feedstocks8. Reduce derivatives9. Catalysis10.Design for degradation11.Real-time analysis for pollution prevention12.Prevent accidents
Anastas, P.T.; Warner, J.C. Green Chemistry: Theory and Practice, New York: Oxford University Press, 1998.
Potential biosynthetic paths to davanone
OO
H
(+)-davanone
OPP
farnesyl diphosphate
oxidation,hydration
OPP
OH O
OOH
hydrolysis,oxidation
conjugateaddition
allylicalkylation
Eric Nacsa, Jonathan Litz