Investigating microscopic interactions to explain ionic liquid effects in
23rd IUPAC Conference on Physical Organic Chemistry (ICPOC23) 3rd – 8th July 2016 • Sydney • Australia
Investigating microscopic interactions to explain ionic liquid effects in bimolecular nucleophilic substitution processes Karin S. Schaffarczyk McHale,a Ronald S. Haines and Jason B. Harper,* a
School of Chemistry, The University of New South Wales, Sydney NSW, Australia *[email protected]
Ionic liquids, salts with normal melting points below 100 ºC,1 have the potential to alter reaction outcomes relative to when a reaction is carried out in a molecular solvent.1, 2 An example of such an effect is seen for the bimolecular nucleophilic substitution reaction between pyridine 1 and benzyl halides 2 (Scheme 1) where a rate enhancement was observed in the presence of the ionic liquid 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([Bmim][N(CF3SO2)2], 3).3, 4 This ionic liquid solvent effect was driven by an entropic benefit caused by interactions between the lone pair of pyridine 1 and the cation of the salt 3.5 Presently there is a general understanding of how varying the constituent ions of ionic liquids affects the cation-nucleophile interaction, allowing increased control of the reaction outcome.6, 7 However, there is currently a limited understanding of other interactions that may be contributing to the observed rate enhancement in these systems. These include key interactions with the transition state, which have been seen to be important in related systems.8
OO CF 3 S S N O O
F 3C
N
N 3
X N
X
N
[Bmim][N(SO 2CF 3)2] 3
R 1
acetonitrile
R 4 X = Cl, Br
2 X = Cl, Br
Scheme 1. Menschutkin reaction between pyridine 1 and each of the benzyl halides 2. (R = p-COCH3, p-CH3, m-CH3, H, p-Br, p-CO2CH3, p-NO2).
Initial results replacing pyridine 1 in Scheme 1 with phosphorus nucleophiles indicate that such interactions significantly contribute to ionic liquid solvent effects in these cases. Through variation of the electrophile, the importance of the extent of charge development in the transition state is being considered. Along with a greater understanding of these 'secondary' interactions, this will expand the predictive framework for ionic liquid solvent effects through an understanding of the effect of varying the nucleophilic heteroatom. References 1. 2. 3. 4. 5. 6. 7. 8.
C. Chiappe, D. Pieraccini, J. Phys. Org. Chem., 2005, 18, 275-297. M. J. Earle, S. P. Katdare, K. R. Seddon, Org. Lett., 2004, 6, 707-710. H. M. Yau, A. G. Howe, J. M. Hook, A. K. Croft, J. B. Harper, Org. Bimol. Chem., 2009, 7, 3572-3575. S. T. Keaveney, J. B. Harper, RSC Adv., 2013, 3, 15698-15704. H. M. Yau, A. K. Croft, J. B. Harper, Faraday Discuss., 2012, 154, 365-371. E. E. L. Tanner, H. M. Yau, R. R. Hawker, A. K. Croft, J. B. Harper, Org. Bimol. Chem., 2013, 11, 6170-6175. S. T. Keaveney, D. V. Francis, W. Cao, R. S. Haines, J. B. Harper, Aust. J. Chem., 2014, 68, 31-35. S. T. Keaveney, R. S. Haines, J. B. Harper, Org. Bimol. Chem., 2015, 13, 3771-3780.
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Investigating microscopic interactions to explain ionic liquid effects in bimolecular nucleophilic substitution processes Karin S. Schaffarczyk McHale,a Ronald S. Haines and Jason B. Harper,* a
School of Chemistry, The University of New South Wales, Sydney NSW, Australia *[email protected]
Ionic liquids, salts with normal melting points below 100 ºC,1 have the potential to alter reaction outcomes relative to when a reaction is carried out in a molecular solvent.1, 2 An example of such an effect is seen for the bimolecular nucleophilic substitution reaction between pyridine 1 and benzyl halides 2 (Scheme 1) where a rate enhancement was observed in the presence of the ionic liquid 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([Bmim][N(CF3SO2)2], 3).3, 4 This ionic liquid solvent effect was driven by an entropic benefit caused by interactions between the lone pair of pyridine 1 and the cation of the salt 3.5 Presently there is a general understanding of how varying the constituent ions of ionic liquids affects the cation-nucleophile interaction, allowing increased control of the reaction outcome.6, 7 However, there is currently a limited understanding of other interactions that may be contributing to the observed rate enhancement in these systems. These include key interactions with the transition state, which have been seen to be important in related systems.8
OO CF 3 S S N O O
F 3C
N
N 3
X N
X
N
[Bmim][N(SO 2CF 3)2] 3
R 1
acetonitrile
R 4 X = Cl, Br
2 X = Cl, Br
Scheme 1. Menschutkin reaction between pyridine 1 and each of the benzyl halides 2. (R = p-COCH3, p-CH3, m-CH3, H, p-Br, p-CO2CH3, p-NO2).
Initial results replacing pyridine 1 in Scheme 1 with phosphorus nucleophiles indicate that such interactions significantly contribute to ionic liquid solvent effects in these cases. Through variation of the electrophile, the importance of the extent of charge development in the transition state is being considered. Along with a greater understanding of these 'secondary' interactions, this will expand the predictive framework for ionic liquid solvent effects through an understanding of the effect of varying the nucleophilic heteroatom. References 1. 2. 3. 4. 5. 6. 7. 8.
C. Chiappe, D. Pieraccini, J. Phys. Org. Chem., 2005, 18, 275-297. M. J. Earle, S. P. Katdare, K. R. Seddon, Org. Lett., 2004, 6, 707-710. H. M. Yau, A. G. Howe, J. M. Hook, A. K. Croft, J. B. Harper, Org. Bimol. Chem., 2009, 7, 3572-3575. S. T. Keaveney, J. B. Harper, RSC Adv., 2013, 3, 15698-15704. H. M. Yau, A. K. Croft, J. B. Harper, Faraday Discuss., 2012, 154, 365-371. E. E. L. Tanner, H. M. Yau, R. R. Hawker, A. K. Croft, J. B. Harper, Org. Bimol. Chem., 2013, 11, 6170-6175. S. T. Keaveney, D. V. Francis, W. Cao, R. S. Haines, J. B. Harper, Aust. J. Chem., 2014, 68, 31-35. S. T. Keaveney, R. S. Haines, J. B. Harper, Org. Bimol. Chem., 2015, 13, 3771-3780.
TH17
