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What’s Your Green Chemistry? #mygreenchem
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“Chemistry & the Economy: 2014 Year-
End Review”
Paul Hodges, Chairman, International eChem
Dr. Mark Jones, Executive External Strategy and Communications
Fellow, Dow Chemical Corporation
Thursday, January 15, 2015
“Rookie Lab Mistakes and Other Facts Not
Found in Textbooks”
Dr. Alison Frontier, Professor of Chemistry, University of Rochester
Bill Courtney, Chemist and Chef, Cheese-Ology
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“Transitioning Organic Synthesis from Organic Solvents to Water”
www.acs.org/acswebinars
Co-produced with the ACS Green Chemistry Institute
Recordings will be available to ACS members after three weeks
Dr. Joseph Fortunak Professor of Chemistry,
Howard University Dr. Bruce Lipshutz Professor of Chemistry,
Univ. of California, Santa Barbara
Bruce H. Lipshutz
Department of Chemistry & Biochemistry
University of California
Santa Barbara, CA 93106 USA
“Transitioning Organic Synthesis
From Organic Solvents to Water”
Co-produced with the
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Smith Jones
Vollhardt & Schore
Soap (as in textbooks)
[spherical micelles]
19
Smith Jones
Vollhardt & Schore
soaps, detergents,
emulsifying agents,
surfactants, etc.
20
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soaps, detergents, emulsifying agents,
surfactants, etc.
Where from?
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Benign by design “designer” surfactants available from Aldrich 22
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Comparisons: PTS, TPGS, and TPGS-750-M
NRC (2000)
Kodak (1954)
Lipshutz (2011)
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PTS
10 nm spheres
&
variable sized worms
TPGS-750-M 60 nm spheres
TPGS-1000 13 nm spheres
Cryo-Transmission Electron Microscopy:
PTS vs. TPGS-750-M vs. TPGS
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12/3/2014
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Chemistry in nanoreactors…in water @ room temperature
O
CH3
CH3
CH3
OO
OO
Me
H3C
CH3 CH3CH3
O
CH3
O
16
reactions take
place here
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TPGS-750-M vs. related surfactants
Ring-Closing Metathesis
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Recycling PTS & TPGS-750-M
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How might PEG in a nonionic surfactant control
the particle size of nanomicelles?
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• by its release from the surfactant into the
surrounding water
• by its length and, therefore, extent of coiling
• by interactions with other PEGs in nearby micelles
• by forming crown ether-like arrays around trace
metals found in water
• it doesn't have anything to do with determining
particle size
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Designer surfactant technologies; in water @ RT
Can the impact be quantified?
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E Factors: What’s Possible with this Technology
E Factor =kg of waste
kg of desired product
typically 5-100 for pharma and fine chemicals
(does not include water)
I
Br
B(OH)2
Br
Org. Proc. Res. Dev. 2003, 7, 362
2 wt % TPGS-750-M/H2O (1 M)
12 h, rt
PdCl2(dtbpf) (1 mol %), Et3N
aq. Na2CO3/acetone, ∆, 12 h
Pd(OAc)2 (5 mol %)Ph3P (10 mol %) (80%)
(93%)
+
Suzuki-Miyaura Coupling
pharma
[ Lipshutz, Isley, Fennewald, Slack, Angew. Chem., Int. Ed. 2013, 52, 10911 ] 32
12/3/2014
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E Factor =kg of waste
kg of desired product
typically 5-100 for pharma and fine chemicals
(does not include water)
I
Br
B(OH)2
Br
Org. Proc. Res. Dev. 2003, 7, 362
2 wt % TPGS-750-M/H2O (1 M)
12 h, rt
PdCl2(dtbpf) (1 mol %), Et3N
aq. Na2CO3/acetone, ∆, 12 h
Pd(OAc)2 (5 mol %)Ph3P (10 mol %) (80%)
(93%)
+
Suzuki-Miyaura Coupling
pharma
E Factors: What’s Possible with this Technology
33
E Factors: What’s possible with Recycling
Suzuki-Miyaura Coupling
N N
ClCl
Pd(PPh3)4, aq. Na2CO3
N N
Cl
CF3
(41%)
2 wt % TPGS-750-M/H2O (1 M)
Et3N (3 equiv), rt
(68%)
(45%)J. Med. Chem. 2007, 50, 3497
+
Pd(dtbpf)Cl2 (2 mol %)
CH3CN, 80 °C
(recycled)
CF3
(HO)2B
pharma
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12/3/2014
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E Factors as a measure of greenness used in this
discussion may not tell the whole story. Why not?
35
• they misrepresent the true nature of organic waste
• they do not consider the origins of materials being
used in reactions
• they do not include salts present, or formed, in a
reaction
• they involve too many mathematical assumptions and
unknowns
• they originated in Europe
Heck Coupling
H2N
I
CN
Pd/C (0.5 mol %) (81%)
5 wt % PTS/H2O (1 M)
Et3N (3 equiv), 60 °C, 3 M NaCl
(76%)
(69%)
+
Pd(t-Bu3P)2 (7.5 mol %)
NaOAc (1.2 equiv), DMA, 140 °C
H2N
CN
(recycled)Org. Proc. Res. and Dev. 2008, 12, 530
pharma
pharma this work
16.7
31.1
2.5
10.2
based on:
total organic solvent
aqueous workup included 2.8
with recycle
2.8
E Factors
E Factors: What’s possible with Recycling
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Designer surfactant technologies; in water @ RT
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Aminations in PTS or TPGS-750-M, in Water @ RT
Lipshutz, B.H.; Chung, D.; Rich, B. Adv. Synth. Catal. 2009, 351, 1717. 38
12/3/2014
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Aminations: Couplings with carbamates
in water @ RT
Isley, Dobarco, Lipshutz, Green Chem. 2014, 16, 1480. 39
Couplings in water @ RT to 50 °C
Salome, C.; Schmitt, M. et al. Green Chem. 2014, 16, 4170. alkyl amines
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C-O Bond construction:
Handa, S.; Lippincott, D. J.; Aue, D. H.; Lipshutz, B. H. Angew. Chem., Int. Ed. 2014, 53, 10658.
Asymmetric lactonizations
O
O
O
97%, 96% ee
OO
Cl
Cl
95%, 90% ee
O
88%, 91% ee
O
41
Trifluoromethylations
NaSO2CF3 = Langlois reagent
Baran, P. S. et al. PNAS 2011, 108, 14411.
Fennewald, J. C.; Lipshutz, B. H. Green Chem. 2014, 16, 1097.
C-C Bond-forming reactions in water @ RT
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olefin metathesis
Klumphu, P.; Lipshutz, B. H. J. Org. Chem. 2014, 79, 888.
C-C Bond-forming reactions in water @ RT
OTBS
+
O
(3 equiv)
Grubbs-2 (2 mol %)
2 wt % surfactant/H2O, rt, 12 h
OTBSO
N N
Ru
Ph
P
Cl
Cl
Surfactant Time (h)
2.0 wt % TPGS-750-M
2.0 wt % Nok
0.02 M KHSO4 /2.0 wt % TPGS-750-M
0.02 M KHSO4 /2.0 wt % Nok
Conversion (%)a
12
12
4
4
76
86
84
a by 1H NMR
77
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reaction appearance
Olefin metathesis reactions in water @ RT
44
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What is the key reaction parameter associated with
micellar catalysis not usually of consequence in
traditional reactions in organic solvents?
45
• greater solubility of organic substrates in water
• pH of the water
• use of a rigorously dried Ar atmosphere
• lipophilicity of the reaction components
• use of room temperature as defined in Southern California
Negishi-like couplings
C-C bond-forming reactions in water @ RT
Zn 46
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Negishi couplings
Krasovskiy, A.; Duplais, C.; Lipshutz, B. H. J. Am. Chem. Soc. 2009, 131, 15592.
C-C bond-forming reactions in water @ RT
Duplais, C.; Krasovskiy, A.; Lipshutz, B. H. Organomet. 2011, 30, 6090. Zn
47
Summary
Potential bonuses:
modified impurity profile
throughput
“The best solvent is no solvent
and if a solvent (diluent) is needed
then water is preferred."
Lower E Factors = sustainability + $
Still running reactions in organic solvents? What’s your E Factor?
48
12/3/2014
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Acknowledgements
NIH, NSF
Takasago (Hideo Shimizu), Sigma-Aldrich (Chris Thomas, Subir Ghorai)
Johnson Matthey (Tom Colacot)
49
50
“Transitioning Organic Synthesis from Organic Solvents to Water”
www.acs.org/acswebinars
Co-produced with the ACS Green Chemistry Institute
Recordings will be available to ACS members after three weeks
Dr. Joseph Fortunak Professor of Chemistry,
Howard University Dr. Bruce Lipshutz Professor of Chemistry,
Univ. of California, Santa Barbara
12/3/2014
26
What’s Your Green Chemistry? #mygreenchem
51 Check out the videos at http://ow.ly/FfxQg and the guidelines at http://ow.ly/Ffy5Y
Share your Green Chem…Blog it. Film it. Picture it.
Upcoming ACS GCI Webinars
52
®
Discover more about ACS GCI at www.acs.org/content/acs/en/greenchemistry
Thursday, March 5, 2015
Thursday, July 16, 2015
Thursday, September 10, 2015
Thursday, December 3, 2015
12/3/2014
27
Upcoming ACS Webinars www.acs.org/acswebinars
53
®
Contact ACS Webinars ® at [email protected]
Thursday, December 11, 2014
“Chemistry & the Economy: 2014 Year-
End Review”
Paul Hodges, Chairman, International eChem
Dr. Mark Jones, Executive External Strategy and Communications
Fellow, Dow Chemical Corporation
Thursday, January 15, 2015
“Rookie Lab Mistakes and Other Facts Not
Found in Textbooks”
Dr. Alison Frontier, Professor of Chemistry, University of Rochester
Bill Courtney, Chemist and Chef, Cheese-Ology
54
“Transitioning Organic Synthesis from Organic Solvents to Water”
www.acs.org/acswebinars
Co-produced with the ACS Green Chemistry Institute
Recordings will be available to ACS members after three weeks
Dr. Joseph Fortunak Professor of Chemistry,
Howard University Dr. Bruce Lipshutz Professor of Chemistry,
Univ. of California, Santa Barbara
12/3/2014
28
Be a featured fan on an upcoming webinar! Write to us @ [email protected]
55
How has ACS Webinars benefited you?
®
“ACS Webinars are entertaining and
often times very informative and
applicable to my career. Watching ACS
Webinars have enriched my knowledge.”
Jackie Le
Scientist, Chemical Development,
Neurocrine Biosciences
56
facebook.com/acswebinars
@acswebinars
youtube.com/acswebinars
12/3/2014
29
Benefits of ACS Membership
57 www.acs.org/2joinACS
Chemical & Engineering News (C&EN) The preeminent weekly news source.
NEW! Free Access to ACS Presentations on Demand® ACS Member only access to over 1,000 presentation recordings from recent ACS meetings and select events.
NEW! ACS Career Navigator Your source for leadership development, professional education, career services, and much more.
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ACS Webinars does not endorse any products or
services. The views expressed in this
presentation are those of the presenter and do
not necessarily reflect the views or policies of the
American Chemical Society.
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Contact ACS Webinars ® at [email protected]
12/3/2014
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Upcoming ACS Webinars www.acs.org/acswebinars
59
®
Contact ACS Webinars ® at [email protected]
Thursday, December 11, 2014
“Chemistry & the Economy: 2014 Year-
End Review”
Paul Hodges, Chairman, International eChem
Dr. Mark Jones, Executive External Strategy and Communications
Fellow, Dow Chemical Corporation
Thursday, January 15, 2015
“Rookie Lab Mistakes and Other Facts Not
Found in Textbooks”
Dr. Alison Frontier, Professor of Chemistry, University of Rochester
Bill Courtney, Chemist and Chef, Cheese-Ology