Physi Pc lae la Cs eh ed mo ins ot tr ya dC j hu se tm mi ca ar lg iPn hs ysics
Page 10 of 11
ARTICLE
Journal Name
1
Although neither the IL nor HOAc is a good solvent to dissolve
ibuprofen (in its free acid form), its solubility increases in
and K. R. Seddon, Phys. Chem. Chem. Phys., 2008, 10, 2972.
DOI: 10.1039/C7CP04078D
1
1
5 K. Bica and R. D. Rogers, Chem. Commun., 2010, 46, 1215.
6 G. J. Maximo, R. J. B. N. Santos, J. A. Lopes-da-Silva, M. C.
Costa, A. J. A. Meirelles and J. A. P. Coutinho, ACS Sustainable
Chem. Eng., 2014, 2, 672.
7 M. S. Miran, H. Kinoshita, T. Yasuda, Md. A. B. H. Susan and M.
Watanabe, Phys. Chem. Chem. Phys., 2012, 14, 5178.
mixtures of [C
free lidocaine in the [C
with the amine molar fraction, likely by weakening the strength
of C NH as an hydrogen-bond donor. Interestingly, the addition
4
NH
3
][OAc] and HOAc. Likewise, the solubility of
4
NH ][OAc] and C NH mixtures increases
3
4
2
1
1
4
2
of an acid API, such as ibuprofen, to a mixture with excess of
8 B. Nuthaki, T. L. Greaves, I. Krodkiewska, A. Weerwardena, M.
I. Burgar, R. J. Mulder and C. J. Drummond, Aust. J. Chem.,
+
4
C NH
2
induces the crystallization of the API as a [C
4
NH
3
] salt
while the addition of lidocaine, the free base of the API, to
2
007, 60, 21.
mixtures with excess of HOAc induces crystallization of the API 19 M. Shen, Y. Zhang, K. Chen, S. Che, J. Yao and H. Li, J. Phys.
Chem. B, 2017, 121, 1372.
in its pure form.
2
2
0 M. Yoshizawa, W. Xu and C. A. Angell, J. Am. Chem. Soc., 2003,
All in all, this study illustrates that adding an acid or a base to a
protic IL can result in ion oligomerization and thus change the
speciation in the system, leading to solvents with tunable
1
25, 15411.
1 P. D. McCrary, P. A. Beasley, G. Gurau, A. Narita, P. S. Barber,
O. A. Cojocaru and R. D. Rogers, New J. Chem., 2013, 37, 2196.
physicochemical properties, useful for many industrial 22 Apex3, version 2015-R7, Bruker-AXS: Madison, WI, 2015
(
Accessed 04/22/2017).
processes. The nature of this change is flexible, as the ions tend
to interact with their conjugate acid or base selectively to
produce different types of oligomeric ions depending on what
is added. In particular, the synthesis and purification of APIs in
2
2
3 SADABS, An Empirical Absorption Correction Program, v.2.01.,
Bruker AXS Inc., Madison, WI, 2001.
4 G. M. Sheldrick, SHELXTL, Structure Determination Software
Suite, v.6.10., Bruker AXS Inc., Madison, WI, 2001.
pharmaceutical processes might be benefit by these tunable 25 C. F. Macrae, I. J. Bruno, J. A. Chisholm, P. R. Edgington, P.
McCabe, E. Pidcock, L. Rodriguez-Monge, R. Taylor, J. van de
solvents, allowing the solubilization and crystallization of pure
APIs with only two chemicals, solely by controlling their ratio.
Streek and P. A. Wood, J. Appl. Crystallogr., 2008, 41, 466.
2
2
2
2
6 M. Lin, M. Tesconi and M. Tischler, Int. J. Pharm., 2009, 369,
4
7.
7 M. Yoshizawa, W. Xu and C. A. Angell, J. Am. Chem. Soc., 2003,
25, 15411.
Acknowledgements
We thank the Novartis-Massachusetts Institute of Technology
1
8 S. P. Kelley, A. Narita, J. D. Holbrey, K. D. Green, W. M. Reichert
and R. D. Rogers, Cryst. Growth Des., 2013, 13, 965.
(MIT) Center for Continuous Manufacturing (CCM) and Novartis
9 Y. Fukaya, Y. Iizuka, K. Sekikawa and H. Ohno, Green Chem.,
International AG for financial support. This research was
2
007, 9, 1155.
undertaken, in part, thanks to funding from the Canada 30 S. Fendt, S. Padmanabhan, H. W. Blanch and J. M. Prausnitz, J.
Chem. Eng. Data, 2011, 56, 31.
1 A. P. Abbott, D. Boothby, G. Capper, D. L. Davies and R. K.
Rasheed, J. Am. Chem. Soc., 2004, 126, 9142.
Excellence Research Chairs Program.
3
3
2 G. Gurau, H. Rodríguez, S. P. Kelley, P. Janiczek, R. S. Kalb and
R. D. Rogers, Angew. Chem. Int. Ed., 2011, 50, 12024.
Notes and references
1
2
3
4
5
R. Hayes, G. G. Warr and R. Atkin, Chem. Rev., 2015, 115
357.
,
33 A. D. Headley and N. M. Jackson, J. Phys. Org. Chem., 2002, 15
52.
,
6
J. G. Huddleston, A. E. Visser, W. M. Reichert, H. D. Willauer, 34 F. Quils and A. Burneau, Vib. Spectrosc., 1998, 16, 105.
G. A. Broker and R. D. Rogers, Green Chem., 2001,
3
, 156.
35 T. Morimoto, J. Imai and M. Nagao, J. Phys. Chem., 1974, 78
,
H. Rodríguez, Ed. Ionic Liquids for Better Separation Processes,
Springer-Verlag Berlin Heidelberg, Heidelberg, 2016.
H. Niedermeyer, J. P. Hallett, I. J. Villar-Garcia, P. A. Hunt and
T. Welton, Chem. Soc. Rev., 2012, 41, 7780.
704.
36 Y. Geng, T. Wang, D. Yu, C. Peng, H. Liu and Y. Hu, Chinese J.
Chem. Eng., 2008, 16, 256.
37 G. Annat, M. Forsyth and D. R. MacFarlane, J. Phys. Chem. B,
2012, 116, 8251.
A. B. Pereiro, J. M. M. Araújo, F. S. Oliveira, C. E. S. Bernardes,
J. M. S. S. Esperança¸ J. N. C. Lopes, I. M. Marrucho and L. P. 38 K. R. Seddon, A. Stark and M.-J. Torres, Pure Appl. Chem.,
N. Rebelo, Chem. Commun., 2012, 48, 3656.
M. Y. Lui, L. Crowhurst, J. P. Hallett, P. A. Hunt, H. Niedermeyer 39 J. Wang, Y. Tian, Y. Zhao and K. Zhuo, Green Chem., 2003,
and T. Welton, Chem. Sci., 2011, , 1491.
618.
M. Smiglak, N. J. Bridges, M. Dilip and R. D. Rogers, Chem. Eur. 40 M. Geppert-Rybczyńska, J. K. Lehmann and A. Heintz, J. Chem.
J., 2008, 14, 11314.
Thermodyn., 2014, 71, 171.
G. Chatel, J. F. B. Pereira, V. Debbeti, H. Wang and R. D. 41 J. Wang, A. Zhu, Y. Zhao and K. Zhuo, J. Solution Chem., 2005,
Rogers, Green Chem., 2014, 16, 2051.
34, 585.
H. Wang, J. F. B. Pereira, A. S. Myerson and R. D. Rogers, ECS 42 Y. Zhong, H. Wang and K. Diao, J. Chem. Thermodyn., 2007, 39
Trans., 2014, 64, 33.
291.
2000, 72, 2275.
6
7
8
9
1
5,
2
,
0 H. Wang, S. P. Kelley, J. W. Brantley, G. Chatel, J. Shamshina, 43 U. Domańska, A. Pobudkowska, A. Pelczarska and P. Gierycz,
J. F. B. Pereira, V. Debbeti, A. S. Myerson and R. D. Rogers,
ChemPhysChem, 2015, 16, 993.
1 H. Wang, P. Berton, A. S. Myerson and R. D. Rogers, ECS Trans.,
J. Phys. Chem. B, 2009, 113, 8941.
44 H. Sjöberg, K. Karami, P. Beronius and L.-O. Sundelöf, Int. J.
Pharm., 1996, 141, 63.
45 Z. Wojnarowska, K. J. Paluch, E. Shoifet, C. Schick, L. Tajber, J.
Knapik, P. Wlodarczyk, K. Grzybowska, S. Hensel-Bielowka, S.
P. Verevkin and M. Paluch, J. Am. Chem. Soc., 2015, 137, 1157.
1
1
1
2
016, 75, 451.
2 J. Wang, T. L. Greaves, D. F. Kennedy, A. Weerawardena, G.
Song and C. J. Drummond, Aust. J. Chem., 2011, 64, 180.
3 T. L. Greaves and C. J. Drummond, Chem. Rev., 2008, 108, 206.
1
0 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins