Organic Process Research & Development
Article
Vries, T.; Whipple, D. A.; Wilcox, G. Org. Process Res. Dev. 2003, 7, 115−
120.
(4) Anelli, P. L.; Biffi, C.; Montanari, F.; Quici, S. J. Org. Chem. 1987,
(18) Lewis, B.; Elbe, G. v. Combustion, Flames and Explosions of Gases,
2nd ed.; Academic Press Inc.: New York, 1961; pp 228−261.
(19) Schroder, V.; Molnarne, M. J. Hazard. Mater. 2005, 121, 37−44.
̈
(20) Brooks, M. R.; Crowl, D. A. J. Loss Prev. Proc. Ind. 2007, 20, 144−
150.
(21) Ongoing studies suggest the LOC of toluene decreases by 1−2%
at elevated pressures. More extensive analysis of LOC values for
different solvents at different pressures will be the focus of a forthcoming
publication.
52, 2559−2562.
(5) Ciriminna, R.; Pagliaro, M. Org. Process Res. Dev. 2010, 14, 245−
251.
(6) Fritz-Langhals, E. Org. Process Res. Dev. 2005, 9, 577−582.
(7) Bogdan, A.; McQuade, D. T. Beilstein J. Org. Chem. 2009, 5,
No. 10.3762/bjoc.5.17.
(22) Chen, L.; Tian, Y. S.; Karayiannis, T. G. Int. J. Heat Mass Transfer
2006, 49, 4220−4230.
(8) For context, see the following: (a) Constable, D. J. C.; Dunn, P. J.;
Hayler, J. D.; Humphrey, G. R.; Leazer, J. L.; Linderman, R. J.; Lorenz,
K.; Manley, J.; Pearlman, B. A.; Wells, A.; Zaks, A.; Zhang, T. Y. Green
Chem. 2007, 9, 411−420. (b) Carey, J. S.; Laffan, D.; Thomson, C.;
Williams, M. T. Org. Biomol. Chem. 2006, 4, 2337−2347. (c) Caron, S.;
Dugger, R. W.; Ruggeri, S. G.; Ragan, J. A.; Ripin, D. H. B. Chem. Rev.
2006, 106, 2943−2989.
(23) Slug flow in the small diameter tubing at these low flow rates was
observed using a small segment of glass tubing at Eli Lilly. Slug flow has
also been observed using Teflon tubing and a colored solution.
(24) The nCSTR model is a simplified two-parameter reactor model
that treats local mixing as being produced by multiple equal-volume
CSTRs in series. For example, behavior of a 50 mL tubular reactor might
be approximated by 100 CSTRs (0.50 mL volume each) in series to
model how the actual RTD deviates from ideal plug flow behavior.
(25) Independent deactivation studies were not performed with each
alcohol, but one would expect that different alcohols might lead to
different deactivation parameters (cf. eq 3).
(9) For relevant reviews, see: (a) Mallat, T.; Baiker, A. Chem. Rev. 2004,
́ ́
104, 3037−3058. (b) Marko, I. E.; Giles, P. R.; Tsukazaki, M.; Chelle-
Regnaut, I.; Gautier, A.; Dumeunier, R.; Philippart, F.; Doda, K.;
Mutonkole, J.-L.; Brown, S. M.; Urch, C. J. Adv. Inorg. Chem. 2004, 56,
211−240. (c) Zhan, B.-Z.; Thompson, A. Tetrahedron 2004, 60, 2917−
2935. (d) Schultz, M. J.; Sigman, M. S. Tetrahedron 2006, 62, 8227−
8241. (e) Matsumoto, T.; Ueno, M.; Wang, N.; Kobayashi, S. Chem.
Asian J. 2008, 3, 196−214. (f) Parmeggiani, C.; Cardona, F. Green Chem.
2012, 14, 547−564. (g) Ryland, B. L.; Stahl, S. S. Angew. Chem., Int. Ed.
2014, 53, 8824−8838.
(26) Photos are available in the Supporting Information.
(10) Ye, X.; Johnson, M. D.; Diao, T.; Yates, M. H.; Stahl, S. S. Green
Chem. 2010, 12, 1180−1186.
(11) Greene, J. F.; Hoover, J. M.; Mannel, D. S.; Root, T. W.; Stahl, S. S.
Org. Process Res. Dev. 2013, 17, 1247−1251.
(12) For other examples of flow-based aerobic oxidation methods, see
the following leading references: (a) Bavykin, D. V.; Lapkin, A. A.;
Kolaczkowski, S. T.; Plucinski, P. K. Appl. Catal., A 2005, 288, 175−184.
(b) Wang, N.; Matsumoto, T.; Ueno, M.; Miyamura, H.; Kobayashi, S.
Angew. Chem., Int. Ed. 2009, 48, 4744−4746. (c) Chapman, A. O.; Akien,
G. R.; Arrowsmith, N. J.; Licence, P.; Poliakoff, M. Green Chem. 2010,
12, 310−315. (d) Aellig, C.; Scholz, D.; Hermans, I. ChemSusChem
2012, 5, 1732−1736. (e) Hamano, M.; Nagy, K. D.; Jensen, K. F. Chem.
Commun. 2012, 48, 2086−2088. (f) Aellig, C.; Scholz, D.; Conrad, S.;
Hermans, I. Green Chem. 2013, 15, 1975−1980. (g) Liu, X.; Jensen, K. F.
Green Chem. 2013, 15, 1538−1541. (h) Obermayer, D.; Balu, A. M.;
Romero, A. A.; Goessler, W.; Luque, R.; Kappe, C. O. Green Chem. 2013,
15, 1530−1537. (i) Gutmann, B.; Elsner, P.; Roberge, D.; Kappe, C. O.
ACS Catal. 2013, 3, 2669−2676. (j) Ushakov, D. B.; Gilmore, K.;
Kopetzki, D.; McQuade, D. T.; Seeberger, P. H. Angew. Chem., Int. Ed.
2014, 53, 557−561. (k) He, Z.; Jamison, T. F. Angew. Chem., Int. Ed.
2014, 53, 3353−3357.
(13) For continuous process examples, see: (a) Kawaguchi, T.; Miyata,
H.; Ataka, K.; Mae, K.; Yoshida, J. Angew. Chem., Int. Ed. 2005, 44,
2413−2416. (b) Baxendale, I. R.; Deeley, J.; Griffiths-Jones, C. M.; Ley,
S. V.; Saaby, S.; Tranmer, G. K. Chem. Commun. 2006, 2566−2568.
(c) Johnson, M. D.; May, S. A.; Calvin, J. R.; Remacle, J.; Stout, J. R.;
Diseroad, W. D.; Zaborenko, N.; Haeberle, B. D.; Sun, W.-M.; Miller, M.
T.; Brennan, J. Org. Process Res. Dev. 2012, 16, 1017−1038.
(14) For continuous processing scale-up reviews, see: (a) Anderson, N.
G. Org. Process Res. Dev. 2001, 5, 613−621. (b) Wiles, C.; Watts, P. Green
Chem. 2012, 14, 38−54.
(15) (a) Yamaguchi, K.; Mori, K.; Mizugaki, T.; Ebitani, K.; Kaneda, K.
J. Am. Chem. Soc. 2000, 122, 7144−7145. (b) Ji, H.; Mizugaki, T.;
Ebitani, K.; Kaneda, K. Tetrahedron Lett. 2002, 43, 7179−7183.
(c) Yamaguchi, K.; Mizuno, N. Angew. Chem., Int. Ed. 2002, 41,
4720−4724. (d) Yamaguchi, K.; Mizuno, N. Chem.Eur. J. 2003, 9,
4353−4361. (e) Mizuno, N.; Yamaguchi, K. Catal. Today 2008, 132,
18−26. (f) Yamaguchi, K.; Kim, J. W.; He, J.; Mizuno, N. J. Catal. 2009,
268, 343−349.
(16) Zotova, N.; Hellgardt, K.; Kelsall, G. H.; Jessiman, A. S.; Hii, K. K.
Green Chem. 2010, 12, 2157−2163.
́
(17) Wu, Y.; Khadilkar, M. R.; Al-Dahhan, M. H.; Dudukovic, M. P.
Ind. Eng. Chem. Res. 1996, 35, 397−405.
1508
dx.doi.org/10.1021/op5002676 | Org. Process Res. Dev. 2014, 18, 1503−1508