Jamison, T. F. et al.: 2018 Science of Synthesis, 2018/5: Flow Chemistry in Organic Synthesis DOI: 10.1055/sos-SD-228-00002
Flow Chemistry in Organic Synthesis

2 Flow Chemistry System Design and Automation

More Information

Book

Editors: Jamison, T. F.; Koch, G.

Authors: Beeler, A. B.; Beingessner, R. L.; Bottecchia, C.; Browne, D. L.; Coley, C. W.; Ferguson, S.; Folgueiras-Amador, A. A.; Gilmore, K.; Hicklin, R. W.; Imbrogno, J.; Itsuno, S.; Jamison, T. F.; Jensen, K. F.; Kelly, L. P.; Kerr, M. S.; Kiesman, W. F.; Kim, H.; Kwok, D.-I. A.; Ley, S. V.; Longstreet, A. R.; May, S. A. ; McTeague, T. A.; Mijalis, A. J.; Mo, Y.; Moon, S.; Myerson, A.; Noël, T.; O’Brien, A. G.; O’Brien, M.; O’Mahony, M.; Opalka, S. M.; Pentelute, B. L.; Polyzos, A. ; Schepartz, A.; Seeberger, P. H.; Seo, H.; Steinauer, A.; Stelzer, T.; Stephenson, C. R. J.; Strom, A. E.; Styduhar, E. D.; Sun, A. C.; Telmesani, R.; Thomas, D. A.; Tran, T. H.; Ullah, M. S.; Wicker, A. C.; Wirth, T.; Yoshida, J.

Title: Flow Chemistry in Organic Synthesis

Print ISBN: 9783132423312; Online ISBN: 9783132423350; Book DOI: 10.1055/b-006-161272

Subjects: Organic Chemistry;Chemical Reactions, Catalysis;Organometallic Chemistry;Laboratory Techniques, Stoichiometry

Science of Synthesis Reference Libraries



Parent publication

Title: Science of Synthesis

DOI: 10.1055/b-00000101

Series Editors: Fürstner (Editor-in-Chief), A.; Carreira, E. M.; Faul, M.; Kobayashi, S.; Koch, G.; Molander, G. A.; Nevado, C.; Trost, B. M.; You, S.-L.

Type: Multivolume Edition

 


Abstract

Organic chemistry performed in continuous-flow equipment, flow chemistry, has emerged as a complementary tool to traditional batch synthesis. This chapter describes typical components of a flow chemistry platform (e.g., pumps, mixers, reactors, and separators), reviews reaction engineering fundamentals as they apply to flow chemistry (e.g., mixing, dispersions, mass and heat transfer), summarizes laboratory and production reactors for single-phase, multiphase, thermal, photochemical, and electrochemical reactions, and describes strategies for separation with a focus on extraction. The chapter also reviews systems for multistep reactions along with integrated flow platforms comprising flow reactors, analytics, and computer control for automation, screening, and optimization.

 
  • 1 Stankiewicz AI, Moulijn JA. Chem. Eng. Prog 2000; 22
  • 2 Górak A, Stankiewicz A. Annu. Rev. Chem. Biomol. Eng 2011; 2: 431
  • 3 Hessel V. Chem. Eng. Technol 2009; 32: 1655
  • 4 Micro Process Engineering: A Comprehensive Handbook. Hessel V, Renken A, Schouten JC, Yoshida J.-I. Wiley-VCH; Weinheim, Germany 2009. 1–3.
  • 5 Jensen KF, Reizman BJ, Newman SG. Lab Chip 2014; 14: 3206
  • 6 Kitson PJ, Glatzel S, Cronin L. Beilstein J. Org. Chem 2016; 12: 2776
  • 7 Jensen KF. AIChE J 2017; 63: 858
  • 8 Gutmann B, Cantillo D, Kappe CO. Angew. Chem. Int. Ed 2015; 54: 6688
  • 9 Hessel V, Kralisch D, Kockmann N, Noël T, Wang Q. ChemSusChem 2013; 6: 746
  • 10 Ley SV, Fitzpatrick DE, Myers RM, Battilocchio C, Ingham RJ. Angew. Chem. Int. Ed 2015; 54: 10122
  • 11 Ley SV, Fitzpatrick DE, Ingham RJ, Myers RM. Angew. Chem. Int. Ed 2015; 54: 3449
  • 12 Movsisyan M, Delbeke EIP, Berton JKET, Battilocchio C, Ley SV, Stevens CV. Chem. Soc. Rev 2016; 45: 4892
  • 13 Plutschack MB, Pieber B, Gilmore K, Seeberger PH. Chem. Rev 2017; 117: 11796
  • 14 Yoshida J.-I, Takahashi Y, Nagaki A. Chem. Commun. (Cambridge) 2013; 49: 9896
  • 15 Hartman RL, McMullen JP, Jensen KF. Angew. Chem. Int. Ed 2011; 50: 7502
  • 16 Bedore MW, Zaborenko N, Jensen KF, Jamison TF. Org. Process Res. Dev 2010; 14: 432
  • 17 Deen WM. Analysis of Transport Phenomena. Oxford University Press; New York 1998
  • 18 Danckwerts PV. Chem. Eng. Sci 1953; 2: 1
  • 19 Trachsel F, Günther A, Khan S, Jensen KF. Chem. Eng. Sci 2005; 60: 5729
  • 20 Hornung CH, Mackley MR. Chem. Eng. Sci 2009; 64: 3889
  • 21 Fogler HS. Elements of Chemical Reaction Engineering. Prentice Hall; Boston 2016
  • 22 Mo Y, Jensen KF. React. Chem. Eng 2016; 1: 501
  • 23 Chapman MR, Kwan MHT, King G, Jolley KE, Hussain M, Hussain S, Salama IE, González Niño C, Thompson LA, Bayana ME, Clayton AD, Nguyen BN, Turner NJ, Kapur N, Blacker AJ. Org. Process Res. Dev 2017; 21: 1294
  • 24 Aris R. Proc. R. Soc. London, Ser. A 1956; 235: 67
  • 25 Nagy KD, Shen B, Jamison TF, Jensen KF. Org. Process Res. Dev 2012; 16: 976
  • 26 Günther A, Jensen KF. Lab Chip 2006; 6: 1487
  • 27 Losey MW, Schmidt MA, Jensen KF. Ind. Eng. Chem. Res 2001; 40: 2555
  • 28 Günther A, Khan SA, Thalmann M, Trachsel F, Jensen KF. Lab Chip 2004; 4: 278
  • 29 Coleman JW, Garimella S. Int. J. Heat Mass Transfer 1999; 42: 2869
  • 30 Qian D, Lawal A. Chem. Eng. Sci 2006; 61: 7609
  • 31 Kashid MN, Agar DW. Chem. Eng. J. (Amsterdam, Neth.) 2007; 131: 1
  • 32 Hawbaker N, Wittgrove E, Christensen B, Sach N, Blackmond DG. Org. Process Res. Dev 2016; 20: 465
  • 33 Zhao C.-X, Middelberg APJ. Chem. Eng. Sci 2011; 66: 1394
  • 34 Yoshida J.-I, Nagaki A, Yamada T. Chem.–Eur. J 2008; 14: 7450
  • 35 Hessel V, Löwe H, Schönfeld F. Chem. Eng. Sci 2005; 60: 2479
  • 36 Schwolow S, Hollmann J, Schenkel B, Röder T. Org. Process Res. Dev 2012; 16: 1513
  • 37 Zaborenko N, Bedore MW, Jamison TF, Jensen KF. Org. Process Res. Dev 2011; 15: 131
  • 38 Saxena AK, Nigam KDP. AIChE J 1984; 30: 363
  • 39 Dong Z, Zhao S, Zhang Y, Yao C, Yuan Q, Chen G. AIChE J 2017; 63: 1404
  • 40 Navarro-Brull FJ, Teixeira AR, Zhang J, Gómez R, Jensen KF. Ind. Eng. Chem. Res 2018; 57: 122
  • 41 Nagaki A, Togai M, Suga S, Aoki N, Mae K, Yoshida J.-I. J. Am. Chem. Soc 2005; 127: 11666
  • 42 Mo Y, Lin H, Jensen KF. Chem. Eng. J. (Amsterdam, Neth.) 2018; 335: 936
  • 43 Ismagilov RF, Stroock AD, Kenis PJA, Whitesides G, Stone HA. Appl. Phys. Lett 2000; 76: 2376
  • 44 Yamaguchi Y, Takagi F, Watari T, Yamashita K, Nakamura H, Shimizu H, Maeda H. Chem. Eng. J. (Amsterdam, Neth.) 2004; 101: 367
  • 45 Hardt S, Drese KS, Hessel V, Schönfeld F. Microfluid. Nanofluid 2005; 1: 108
  • 46 Handbook of Industrial Mixing: Science and Practice. Paul EL, Atiemo-Obeng VA, Kresta SM. Wiley; Hoboken, NJ 2004
  • 47 Schönfeld F, Hessel V, Hofmann C. Lab Chip 2004; 4: 65
  • 48 Kinoshita H, Kaneda S, Fujii T, Oshima M. Lab Chip 2007; 7: 338
  • 49 Haber J, Kashid MN, Renken A, Kiwi-Minsker L. Ind. Eng. Chem. Res 2012; 51: 1474
  • 50 Laue S, Haverkamp V, Mleczko L. Org. Process Res. Dev 2016; 20: 480
  • 51 Westermann T, Mleczko L. Org. Process Res. Dev 2016; 20: 487
  • 52 Schwolow S, Ko JY, Kockmann N, Röder T. Chem. Eng. Sci 2016; 141: 356
  • 54 Jensen KF. Chem. Eng. Sci 2001; 56: 293
  • 55 Adamo A, Beingessner RL, Behnam M, Chen J, Jamison TF, Jensen KF, Monbaliu J.-CM, Myerson AS, Revalor EM, Snead DR, Stelzer T, Weeranoppanant N, Wong SY, Zhang P. Science (Washington, D. C.) 2016; 352: 61
  • 56 Johnson MD, May SA, Haeberle B, Lambertus GR, Pulley SR, Stout JR. Org. Process Res. Dev 2016; 20: 1305
  • 57 Nagaki A, Imai K, Ishiuchi S, Yoshida J.-I. Angew. Chem. Int. Ed 2015; 54: 1914
  • 58 Nagaki A, Ichinari D, Yoshida J.-I. J. Am. Chem. Soc 2014; 136: 12245
  • 59 Kim H, Min K.-I, Inoue K, Im DJ, Kim D.-P, Yoshida J.-I. Science (Washington, D. C.) 2016; 352: 691
  • 60 Inoue T, Schmidt MA, Jensen KF. Ind. Eng. Chem. Res 2007; 46: 1153
  • 61 de Mas N, Günther A, Schmidt MA, Jensen KF. Ind. Eng. Chem. Res 2009; 48: 1428
  • 62 Kumar GS, Pieber B, Reddy KR, Kappe CO. Chem.–Eur. J 2012; 18: 6124
  • 63 Pieber B, Glasnov T, Kappe CO. Chem.–Eur. J 2015; 21: 4368
  • 64 Bottausci F, Cardonne C, Meinhart C, Mezić I. Lab Chip 2007; 7: 396
  • 65 Yang Z, Matsumoto S, Goto H, Matsumoto M, Maeda R. Sens. Actuators, A 2001; 93: 266
  • 66 Bengtsson M, Laurell T. Anal. Bioanal. Chem 2004; 378: 1716
  • 67 Usutani H, Tomida Y, Nagaki A, Okamoto H, Nokami T, Yoshida J.-I. J. Am. Chem. Soc 2007; 129: 3046
  • 68 Dreyfus R, Tabeling P, Willaime H. Phys. Rev. Lett 2003; 90: 144505
  • 69 Yang L, Nieves-Remacha MJ, Jensen KF. Chem. Eng. Sci 2017; 169: 106
  • 70 Song H, Chen DL, Ismagilov RF. Angew. Chem. Int. Ed 2006; 45: 7336
  • 71 Sebastian Cabeza V, Kuhn S, Kulkarni AA, Jensen KF. Langmuir 2012; 28: 7007
  • 72 Naber JR, Buchwald SL. Angew. Chem. Int. Ed 2010; 49: 9469
  • 73 Noël T, Kuhn S, Musacchio AJ, Jensen KF, Buchwald SL. Angew. Chem. Int. Ed 2011; 50: 5943
  • 74 Nieves-Remacha MJ, Kulkarni AA, Jensen KF. Ind. Eng. Chem. Res 2012; 51: 16251
  • 75 Nieves-Remacha MJ, Yang L, Jensen KF. Ind. Eng. Chem. Res 2015; 54: 6649
  • 76 Song H, Bringer MR, Tice JD, Gerdts CJ, Ismagilov RF. Appl. Phys. Lett 2003; 83: 4664
  • 77 Kreutzer MT, Kapteijn F, Moulijn JA, Heiszwolf JJ. Chem. Eng. Sci 2005; 60: 5895
  • 78 van Baten JM, Krishna R. Chem. Eng. Sci 2005; 60: 1117
  • 79 Nieves-Remacha MJ, Kulkarni AA, Jensen KF. Ind. Eng. Chem. Res 2013; 52: 8996
  • 80 Yang L, Shi Y, Abolhasani M, Jensen KF. Lab Chip 2015; 15: 3232
  • 81 Zhang J, Teixeira AR, Jensen KF. AIChE J 2018; 64: 564
  • 82 Murphy ER, Martinelli JR, Zaborenko N, Buchwald SL, Jensen KF. Angew. Chem. Int. Ed 2007; 46: 1734
  • 83 Cantillo D, Kappe CO. React. Chem. Eng 2017; 2: 7
  • 84 Chambers RD, Holling D, Spink RCH, Sandford G. Lab Chip 2001; 1: 132
  • 85 Wada Y, Schmidt MA, Jensen KF. Ind. Eng. Chem. Res 2006; 45: 8036
  • 86 Cranwell PB, OʼBrien M, Browne DL, Koos P, Polyzos A, Peña-López M, Ley SV. Org. Biomol. Chem 2012; 10: 5774
  • 87 OʼBrien M, Baxendale IR, Ley SV. Org. Lett 2010; 12: 1596
  • 88 Polyzos A, OʼBrien M, Petersen TP, Baxendale IR, Ley SV. Angew. Chem. Int. Ed 2011; 50: 1190
  • 89 Yang L, Jensen KF. Org. Process Res. Dev 2013; 17: 927
  • 90 Frost CG, Mutton L. Green Chem 2010; 12: 1687
  • 91 Tanimu A, Jaenicke S, Alhooshani K. Chem. Eng. J. (Amsterdam, Neth.) 2017; 327: 792
  • 92 Hu C, Creaser D, Siahrostami S, Grönbeck H, Ojagh H, Skoglundh M. Catal. Sci. Technol 2014; 4: 2427
  • 93 OʼNeal EJ, Jensen KF. ChemCatChem 2014; 6: 3004
  • 94 Shore G, Morin S, Organ MG. Angew. Chem. Int. Ed 2006; 45: 2761
  • 95 Loudon D, van der Merwe W, Nicol W. Chem. Eng. Sci 2006; 61: 7551
  • 96 Al-Naimi SA, Al-Sudani FTJ, Halabia EK. Chem. Eng. Res. Des 2011; 89: 930
  • 97 Zhang J, Teixeira AR, Kögl LT, Yang L, Jensen KF. AIChE J 2017; 63: 4694
  • 98 Cantillo D, Kappe CO. ChemCatChem 2014; 6: 3286
  • 99 Li P, Moore JS, Jensen KF. ChemCatChem 2013; 5: 1729
  • 100 Peer M, Weeranoppanant N, Adamo A, Zhang Y, Jensen KF. Org. Process Res. Dev 2016; 20: 1677
  • 101 Marchetti P, Jimenez Solomon MF, Szekely G, Livingston AG. Chem. Rev 2014; 114: 10735
  • 102 OʼNeal EJ, Lee CH, Brathwaite J, Jensen KF. ACS Catal 2015; 5: 2615
  • 103 Cambié D, Bottecchia C, Straathof NJW, Hessel V, Noël T. Chem. Rev 2016; 116: 10276
  • 104 Loponov KN, Lopes J, Barlog M, Astrova EV, Malkov AV, Lapkin AA. Org. Process Res. Dev 2014; 18: 1443
  • 105 Hook BDA, Dohle W, Hirst PR, Pickworth M, Berry MB, Booker-Milburn KI. J. Org. Chem 2005; 70: 7558
  • 106 Elliott LD, Berry M, Harji B, Klauber D, Leonard J, Booker-Milburn KI. Org. Process Res. Dev 2016; 20: 1806
  • 107 Justus Liebigs Ann. Chem 1848; 64: 339
  • 108 Horn EJ, Rosen BR, Baran PS. ACS Cent. Sci 2016; 2: 302
  • 109 Badalyan A, Stahl SS. Nature (London) 2016; 535: 406
  • 110 Xu H.-C, Moeller KD. J. Am. Chem. Soc 2008; 130: 13542
  • 111 Ashikari Y, Nokami T, Yoshida J.-I. J. Am. Chem. Soc 2011; 133: 11840
  • 112 OʼBrien AG, Maruyama A, Inokuma Y, Fujita M, Baran PS, Blackmond DG. Angew. Chem. Int. Ed 2014; 53: 11868
  • 113 Kawamata Y, Yan M, Liu Z, Bao D.-H, Chen J, Starr JT, Baran PS. J. Am. Chem. Soc 2017; 139: 7448
  • 114 Horn EJ, Rosen BR, Chen Y, Tang J, Chen K, Eastgate MD, Baran PS. Nature (London) 2016; 533: 77
  • 115 Atobe M, Tateno H, Matsumura Y. Chem. Rev 2018; 118: 4541
  • 116 Suga S, Okajima M, Fujiwara K, Yoshida J.-I. J. Am. Chem. Soc 2001; 123: 7941
  • 117 Suga S, Okajima M, Fujiwara K, Yoshida J.-I. QSAR Comb. Sci 2005; 24: 728
  • 118 Kashiwagi T, Amemiya F, Fuchigami T, Atobe M. Chem. Commun. (Cambridge) 2012; 48: 2806
  • 119 Gütz C, Stenglein A, Waldvogel SR. Org. Process Res. Dev 2017; 21: 771
  • 120 Green RA, Brown RCD, Pletcher D, Harji B. Org. Process Res. Dev 2015; 19: 1424
  • 121 Green RA, Brown RCD, Pletcher D. J. Flow Chem 2015; 5: 31
  • 122 Leung P, Shah AA, Sanz L, Flox C, Morante JR, Xu Q, Mohamed MR, Ponce de León C, Walsh FC. J. Power Sources 2017; 360: 243
  • 123 Mo Y, Jensen KF. Chem.–Eur. J 2018; 24: 10260
  • 124 Peela NR, Lee IC, Vlachos DG. Ind. Eng. Chem. Res 2012; 51: 16270
  • 125 Hartman RL. Org. Process Res. Dev 2012; 16: 870
  • 126 Sedelmeier J, Ley SV, Baxendale IR, Baumann M. Org. Lett 2010; 12: 3618
  • 127 Noël T, Naber JR, Hartman RL, McMullen JP, Jensen KF, Buchwald SL. Chem. Sci 2011; 2: 287
  • 128 Hartman RL, Naber JR, Zaborenko N, Buchwald SL, Jensen KF. Org. Process Res. Dev 2010; 14: 1347
  • 129 Kuhn S, Noël T, Gu L, Heider PL, Jensen KF. Lab Chip 2011; 11: 2488
  • 130 Pamme N. Lab Chip 2006; 6: 24
  • 131 Rodríguez-Villarreal AI, Tarn MD, Madden LA, Lutz JB, Greenman J, Samitier J, Pamme N. Lab Chip 2011; 11: 1240
  • 132 Pamme N, Wilhelm C. Lab Chip 2006; 6: 974
  • 133 Browne DL, Deadman BJ, Ashe R, Baxendale IR, Ley SV. Org. Process Res. Dev 2011; 15: 693
  • 134 Liguori L, Bjørsvik H.-R. Org. Process Res. Dev 2011; 15: 997
  • 135 Spaccini R, Liguori L, Punta C, Bjørsvik H.-R. ChemSusChem 2012; 5: 261
  • 136 Poe SL, Cummings MA, Haaf MP, McQuade DT. Angew. Chem. Int. Ed 2006; 45: 1544
  • 137 Horie T, Sumino M, Tanaka T, Matsushita Y, Ichimura T, Yoshida J.-I. Org. Process Res. Dev 2010; 14: 405
  • 138 Gilmore K, Vukelić S, McQuade DT, Koksch B, Seeberger PH. Org. Process Res. Dev 2014; 18: 1771
  • 139 Kopach ME, Roberts DJ, Johnson MD, McClary Groh J, Adler JJ, Schafer JP, Kobierski ME, Trankle WG. Green Chem 2012; 14: 1524
  • 140 Cole KP, McClary Groh J, Johnson MD, Burcham CL, Campbell BM, Diseroad WD, Heller MR, Howell JR, Kallman NJ, Koenig TM, May SA, Miller RD, Mitchell D, Myers DP, Myers SS, Phillips JL, Polster CS, White TD, Cashman J, Hurley D, Moylan R, Sheehan P, Spencer RD, Desmond K, Desmond P, Gowran O. Science (Washington, D. C.) 2017; 356: 1144
  • 141 Glöckner S, Tran DN, Ingham RJ, Fenner S, Wilson ZE, Battilocchio C, Ley SV. Org. Biomol. Chem 2015; 13: 207
  • 142 Seader JD, Henley EJ. Separation Process Principles. Wiley; New York 1998
  • 143 Cohen Y, Glater J. Desalin. Water Treat 2010; 15: 222
  • 144 Daufin G, Escudier J.-P, Carrère H, Bérot S, Fillaudeau L, Decloux M. Food Bioprod. Process 2001; 79: 89
  • 145 Lee KP, Arnot TC, Mattia D. J. Membr. Sci 2011; 370: 1
  • 146 Hellweg S, Fischer U, Scheringer M, Hungerbühler K. Green Chem 2004; 6: 418
  • 147 Badman C, Trout BL. J. Pharm. Sci 2015; 104: 779
  • 148 Brennan Z. RAPS Regulatory Focus: FDA Allows First Switch From Batch to Continuous Manufacturing for HIV Drug.
  • 149 Adamo A, Heider PL, Weeranoppanant N, Jensen KF. Ind. Eng. Chem. Res 2013; 52: 10802
  • 150 Weeranoppanant N, Adamo A, Saparbaiuly G, Rose E, Fleury C, Schenkel B, Jensen KF. Ind. Eng. Chem. Res 2017; 56: 4095
  • 151 Shen Y, Weeranoppanant N, Xi L, Chen Y, Lusardi MR, Imbrogno J, Bawendi MG, Jensen KF. Nanoscale 2017; 9: 7703
  • 152 Yang L, Weeranoppanant N, Jensen KF. Ind. Eng. Chem. Res 2017; 56: 12184
  • 153 Imbrogno J, Rogers L, Thomas DA, Jensen KF. Chem. Commun. (Cambridge) 2018; 54: 70
  • 154 McMullen JP, Jensen KF. Annu. Rev. Anal. Chem 2010; 3: 19
  • 155 Yue J, Schouten JC, Nijhuis TA. Ind. Eng. Chem. Res 2012; 51: 14583
  • 156 Moore JS, Jensen KF. Org. Process Res. Dev 2012; 16: 1409
  • 157 Carter CF, Lange H, Ley SV, Baxendale IR, Wittkamp B, Goode JG, Gaunt NL. Org. Process Res. Dev 2010; 14: 393
  • 158 Sans V, Porwol L, Dragone V, Cronin L. Chem. Sci 2015; 6: 1258
  • 159 McMullen JP, Stone MT, Buchwald SL, Jensen KF. Angew. Chem. Int. Ed 2010; 49: 7076
  • 160 Holmes N, Akien GR, Savage RJD, Stanetty C, Baxendale IR, Blacker AJ, Taylor BA, Woodward RL, Meadows RE, Bourne RA. React. Chem. Eng 2016; 1: 96
  • 161 Schwolow S, Braun F, Rädle M, Kockmann N, Röder T. Org. Process Res. Dev 2015; 19: 1286
  • 162 Welch CJ, Gong X, Schafer W, Pratt EC, Brkovic T, Pirzada Z, Cuff JF, Kosjek B. Tetrahedron: Asymmetry 2010; 21: 1674
  • 163 Moore JS, Smith CD, Jensen KF. React. Chem. Eng 2016; 1: 272
  • 164 Mascia S, Heider PL, Zhang H, Lakerveld R, Benyahia B, Barton PI, Braatz RD, Cooney CL, Evans JMB, Jamison TF, Jensen KF, Myerson AS, Trout BL. Angew. Chem. Int. Ed 2013; 52: 12359
  • 165 Quon JL, Zhang H, Alvarez A, Evans J, Myerson AS, Trout BL. Cryst. Growth Des 2012; 12: 3036
  • 166 MIT News: Continuous drug manufacturing offers speed, lower costs.
  • 167 Zhang P, Weeranoppanant N, Thomas DA, Tahara K, Stelzer T, Russell MG, OʼMahony M, Myerson AS, Lin H, Kelly LP, Jensen KF, Jamison TF, Dai C, Cui Y, Briggs N, Beingessner RL, Adamo A. Chem.–Eur. J 2018; 24: 2776
  • 168 Dryland A, Sheppard RC. Tetrahedron 1988; 44: 859
  • 169 Mijalis AJ, Thomas III DA, Simon MD, Adamo A, Beaumont R, Jensen KF, Pentelute BL. Nat. Chem. Biol 2017; 13: 464
  • 170 Sans V, Cronin L. Chem. Soc. Rev 2016; 45: 2032
  • 171 Hartman RL, Jensen KF. Lab Chip 2009; 9: 2495
  • 172 Mohamed DKB, Yu X, Li J, Wu J. Tetrahedron Lett 2016; 57: 3965
  • 173 Reizman BJ, Jensen KF. Acc. Chem. Res 2016; 49: 1786
  • 174 Ratner DM, Murphy ER, Jhunjhunwala M, Snyder DA, Jensen KF, Seeberger PH. Chem. Commun. (Cambridge) 2005; 578
  • 175 Sugimoto A, Fukuyama T, Rahman MT, Ryu I. Tetrahedron Lett 2009; 50: 6364
  • 176 Koch K, van Weerdenburg BJA, Verkade JMM, Nieuwland PJ, Rutjes FPJT, van Hest JCM. Org. Process Res. Dev 2009; 13: 1003
  • 177 Box GEP, Hunter WG, Hunter JS. Statistics for Experimenters: An Introduction to Design, Data Analysis, and Model Building. Wiley; Hoboken, NJ 1978
  • 178 Nieuwland PJ, Segers R, Koch K, van Hest JCM, Rutjes FPJT. Org. Process Res. Dev 2011; 15: 783
  • 179 Zheng B, Ismagilov RF. Angew. Chem. Int. Ed 2005; 44: 2520
  • 180 Hatakeyama T, Chen DL, Ismagilov RF. J. Am. Chem. Soc 2006; 128: 2518
  • 181 Wheeler RC, Benali O, Deal M, Farrant E, MacDonald SJF, Warrington BH. Org. Process Res. Dev 2007; 11: 704
  • 182 Benali O, Deal M, Farrant E, Tapolczay D, Wheeler R. Org. Process Res. Dev 2008; 12: 1007
  • 183 Goodell JR, McMullen JP, Zaborenko N, Maloney JR, Ho C.-X, Jensen KF, Porco Jr. JA, Beeler AB. J. Org. Chem 2009; 74: 6169
  • 184 Martin VI, Goodell JR, Ingham OJ, Porco Jr. JA, Beeler AB. J. Org. Chem 2014; 79: 3838
  • 185 Martha CT, Elders N, Krabbe JG, Kool J, Niessen WMA, Orru RVA, Irth H. Anal. Chem 2008; 80: 7121
  • 186 Martha CT, Heemskerk A, Hoogendoorn J.-C, Elders N, Niessen WMA, Orru RVA, Irth H. Chem.–Eur. J 2009; 15: 7368
  • 187 Browne DL, Wright S, Deadman BJ, Dunnage S, Baxendale IR, Turner RM, Ley SV. Rapid Commun. Mass Spectrom 2012; 26: 1999
  • 188 Fang H, Xiao Q, Wu F, Floreancig PE, Weber SG. J. Org. Chem 2010; 75: 5619
  • 189 Hwang Y.-J, Coley CW, Abolhasani M, Marzinzik AL, Koch G, Spanka C, Lehmann H, Jensen KF. Chem. Commun. (Cambridge) 2017; 53: 6649
  • 190 Houben C, Lapkin AA. Curr. Opin. Chem. Eng 2015; 9: 1
  • 191 McMullen JP, Jensen KF. Org. Process Res. Dev 2011; 15: 398
  • 192 Reizman BJ, Jensen KF. Org. Process Res. Dev 2012; 16: 1770
  • 193 Moore JS, Jensen KF. Angew. Chem. Int. Ed 2014; 53: 470
  • 194 Fabry DC, Sugiono E, Rueping M. Isr. J. Chem 2014; 54: 341
  • 195 Krishnadasan S, Brown RJC, deMello AJ, deMello JC. Lab Chip 2007; 7: 1434
  • 196 Huyer W, Neumaier A. ACM Trans. Math. Softw 2008; 35: 9
  • 197 Nelder JA, Mead R. Comput. J 1965; 7: 308
  • 198 McMullen JP, Jensen KF. Org. Process Res. Dev 2010; 14: 1169
  • 199 Bezerra MA, Santelli RE, Oliveira EP, Villar LS, Escaleira LA. Talanta 2008; 76: 965
  • 200 Parrott AJ, Bourne RA, Akien GR, Irvine DJ, Poliakoff M. Angew. Chem. Int. Ed 2011; 50: 3788
  • 201 Skilton RA, Parrott AJ, George MW, Poliakoff M, Bourne RA. Appl. Spectrosc 2013; 67: 1127
  • 202 Kreutz JE, Shukhaev A, Du W, Druskin S, Daugulis O, Ismagilov RF. J. Am. Chem. Soc 2010; 132: 3128
  • 203 Lawler EL, Wood DE. Oper. Res 1966; 14: 699
  • 204 Reizman BJ, Jensen KF. Chem. Commun. (Cambridge) 2015; 51: 13290
  • 205 Reizman BJ, Wang Y.-M, Buchwald SL, Jensen KF. React. Chem. Eng 2016; 1: 658
  • 206 Reizman BJ. 2015
  • 207 Baumgartner LM, Coley CW, Reizman BJ, Gao KW, Jensen KF. React. Chem. Eng 2018; 3: 301
  • 208 Skilton RA, Bourne RA, Amara Z, Horvath R, Jin J, Scully MJ, Streng E, Tang SLY, Summers PA, Wang J, Pérez E, Asfaw N, Aydos GLP, Dupont J, Comak G, George MW, Poliakoff M. Nat. Chem 2015; 7: 1
  • 209 Fitzpatrick DE, Battilocchio C, Ley SV. Org. Process Res. Dev 2016; 20: 386