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1 We will begin momentarily at 2pm ET Recordings will be available to ACS members after three weeks Contact ACS Webinars at 1 Have Questions? Why am I muted? Don t worry. Everyone is muted except the presenter and host. Thank you and enjoy the show. Type them into questions box! Contact ACS Webinars at acswebinars@acs.org 2 1

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5 Beginning in 2014 all recordings of ACS Webinars will be available to current ACS members three weeks after the Live broadcast date. Live weekly ACS Webinars will continue to be available to the general public. Contact ACS Webinars at 9 Upcoming ACS GCI Webinars Thursday, March 5, 2015 Thursday, July 16, 2015 Thursday, September 10, 2015 Thursday, December 3, 2015 Discover more about ACS GCI at

6 What s Your Green Chemistry? #mygreenchem Share your Green Chem Blog it. Film it. Picture it. Check out the videos at and the guidelines at 11 Upcoming ACS Webinars 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 Contact ACS Webinars at acswebinars@acs.org 12 6

7 Transitioning Organic Synthesis from Organic Solvents to Water Dr. Bruce Lipshutz Professor of Chemistry, Univ. of California, Santa Barbara Dr. Joseph Fortunak Professor of Chemistry, Howard University Recordings will be available to ACS members after three weeks Co-produced with the ACS Green Chemistry Institute 13 Transitioning Organic Synthesis From Organic Solvents to Water Bruce H. Lipshutz Department of Chemistry & Biochemistry University of California Santa Barbara, CA USA Co-produced with the 14 7

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10 Soap (as in textbooks) [spherical micelles] Vollhardt & Schore Smith Jones 19 soaps, detergents, emulsifying agents, surfactants, etc. Vollhardt & Schore Smith Jones 20 10

11 soaps, detergents, emulsifying agents, surfactants, etc. Where from? 21 Benign by design designer surfactants available from Aldrich 22 11

12 Comparisons: PTS, TPGS, and TPGS-750-M NRC (2000) Kodak (1954) Lipshutz (2011) 23 Cryo-Transmission Electron Microscopy: PTS vs. TPGS-750-M vs. TPGS PTS 10 nm spheres & variable sized worms TPGS-750-M 60 nm spheres TPGS nm spheres 24 12

13 Chemistry in nanoreactors in room temperature H 3 C reactions take place here CH 3 CH 3 CH 3 O CH 3 CH 3 O O CH 3 CH 3 O O O 16 O Me 25 TPGS-750-M vs. related surfactants Ring-Closing Metathesis 26 13

14 Recycling PTS & TPGS-750-M 27 How might PEG in a nonionic surfactant control the particle size of nanomicelles? 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 28 14

15 Designer surfactant technologies; in RT Can the impact be quantified?

16 31 E Factors: What s Possible with this Technology typically for pharma and fine chemicals E Factor = kg of waste kg of desired product (does not include water) Suzuki-Miyaura Coupling B(OH) 2 I + Br Org. Proc. Res. Dev. 2003, 7, 362 pharma Pd(OAc) 2 (5 mol %) Ph 3 P (10 mol %) (80%) aq. Na 2 CO 3 /acetone,, 12 h PdCl 2 (dtbpf) (1 mol %), Et 3 N 2 wt % TPGS-750-M/H 2 O (1 M) 12 h, rt Br (93%) [ Lipshutz, Isley, Fennewald, Slack, Angew. Chem., Int. Ed. 2013, 52, ] 32 16

17 E Factors: What s Possible with this Technology typically for pharma and fine chemicals E Factor = kg of waste kg of desired product (does not include water) Suzuki-Miyaura Coupling B(OH) 2 I + Br Org. Proc. Res. Dev. 2003, 7, 362 pharma Pd(OAc) 2 (5 mol %) Ph 3 P (10 mol %) (80%) aq. Na 2 CO 3 /acetone,, 12 h PdCl 2 (dtbpf) (1 mol %), Et 3 N 2 wt % TPGS-750-M/H 2 O (1 M) 12 h, rt Br (93%) 33 E Factors: What s possible with Recycling Suzuki-Miyaura Coupling pharma Pd(PPh 3 ) 4, aq. Na 2 CO 3 (41%) (HO) 2 B CF 3 + Cl N N Cl CH 3 CN, 80 C Pd(dtbpf)Cl 2 (2 mol %) Cl N N CF 3 J. Med. Chem. 2007, 50, wt % TPGS-750-M/H 2 O (1 M) Et 3 N (3 equiv), rt (68%) (45%) (recycled) 34 17

18 E Factors as a measure of greenness used in this discussion may not tell the whole story. Why not? 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 35 E Factors: What s possible with Recycling Heck Coupling pharma Pd/C (0.5 mol %) (81%) NaOAc (1.2 equiv), DMA, 140 C H 2 N I + CN Pd(t-Bu 3 P) 2 (7.5 mol %) H 2 N CN Org. Proc. Res. and Dev. 2008, 12, wt % PTS/H 2 O (1 M) Et 3 N (3 equiv), 60 C, 3 M NaCl (76%) (69%) (recycled) E Factors based on: pharma this work with recycle total organic solvent aqueous workup included

19 Designer surfactant technologies; in RT 37 Aminations in PTS or TPGS-750-M, in RT Lipshutz, B.H.; Chung, D.; Rich, B. Adv. Synth. Catal. 2009, 351,

20 Aminations: Couplings with carbamates in RT Isley, Dobarco, Lipshutz, Green Chem. 2014, 16, Couplings in RT to 50 C alkyl amines Salome, C.; Schmitt, M. et al. Green Chem. 2014, 16,

21 C-O Bond construction: Asymmetric lactonizations O O O 97%, 96% ee O O Cl Cl 95%, 90% ee O O 88%, 91% ee Handa, S.; Lippincott, D. J.; Aue, D. H.; Lipshutz, B. H. Angew. Chem., Int. Ed. 2014, 53, C-C Bond-forming reactions in RT Trifluoromethylations NaSO 2 CF 3 = Langlois reagent Fennewald, J. C.; Lipshutz, B. H. Green Chem. 2014, 16, Baran, P. S. et al. PNAS 2011, 108,

22 C-C Bond-forming reactions in RT olefin metathesis OTBS + O 2 wt % surfactant/h 2 O, rt, 12 h Grubbs-2 (2 mol %) OTBS O (3 equiv) N N Cl Cl Ru Ph P Surfactant 2.0 wt % TPGS-750-M 2.0 wt % Nok 0.02 M KHSO 4 /2.0 wt % TPGS-750-M 0.02 M KHSO 4 /2.0 wt % Nok a by 1 H NMR Time (h) Conversion (%) a Klumphu, P.; Lipshutz, B. H. J. Org. Chem. 2014, 79, Olefin metathesis reactions in RT reaction appearance 44 22

23 What is the key reaction parameter associated with micellar catalysis not usually of consequence in traditional reactions in organic solvents? 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 45 C-C bond-forming reactions in RT Negishi-like couplings Zn 46 23

24 C-C bond-forming reactions in RT Negishi couplings Krasovskiy, A.; Duplais, C.; Lipshutz, B. H. J. Am. Chem. Soc. 2009, 131, Zn Duplais, C.; Krasovskiy, A.; Lipshutz, B. H. Organomet. 2011, 30, Summary Still running reactions in organic solvents? What s your E Factor? Lower E Factors = sustainability + $ The best solvent is no solvent and if a solvent (diluent) is needed then water is preferred." Potential bonuses: modified impurity profile throughput 48 24

25 Acknowledgements NIH, NSF Johnson Matthey (Tom Colacot) Takasago (Hideo Shimizu), Sigma-Aldrich (Chris Thomas, Subir Ghorai) 49 Transitioning Organic Synthesis from Organic Solvents to Water Dr. Bruce Lipshutz Professor of Chemistry, Univ. of California, Santa Barbara Dr. Joseph Fortunak Professor of Chemistry, Howard University Recordings will be available to ACS members after three weeks Co-produced with the ACS Green Chemistry Institute 50 25

26 What s Your Green Chemistry? #mygreenchem Share your Green Chem Blog it. Film it. Picture it. Check out the videos at and the guidelines at 51 Upcoming ACS GCI Webinars Thursday, March 5, 2015 Thursday, July 16, 2015 Thursday, September 10, 2015 Thursday, December 3, 2015 Discover more about ACS GCI at

27 Upcoming ACS Webinars 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 Contact ACS Webinars at 53 Transitioning Organic Synthesis from Organic Solvents to Water Dr. Bruce Lipshutz Professor of Chemistry, Univ. of California, Santa Barbara Dr. Joseph Fortunak Professor of Chemistry, Howard University Recordings will be available to ACS members after three weeks Co-produced with the ACS Green Chemistry Institute 54 27

28 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 Be a featured fan on an upcoming webinar! Write to acswebinars@acs.org 55 youtube.com/acswebinars 56 28

29 Benefits of ACS Membership 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 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. Contact ACS Webinars at 58 29

30 Upcoming ACS Webinars 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 Contact ACS Webinars at 59 30