Why is it good to do SN2 reactions in polar aprotic solvents?

1 Answer
Jan 2, 2017

The activity of any solute is moderated by the properties of the solvent in which it is dissolved.


In water, it is well known that the strongest base that can exist is #""^(-)OH# anion. Bases that are nominally stronger than hydroxide, for instance amide ion, would undergo reaction with the solvent:

#""^(-)NH_2 + H_2O(aq) rarr NH_3(aq) + HO^-#

Water is a polar, protic solvent, such that the water molecules stabilize the activity of any anion or cation dissolved in that solution.

With other solvents, say diethyl ether, or ammonia, or even hexanes, the activity of the anion MAY be greatly magnified, and thus this solvent is used as the medium for the reaction. It is well known that hydroxide ion is a much more potent nucleophile when deployed in say diethyl ether, than it is when deployed in water. Why? Because, the ether molecules are much less capable of stabilizing, of solvating, the hydroxide anion. Of course, hydroxide anion might be (in fact it is!) much less soluble in ether than it is in water.

With many solvents, e.g. water, ethers, DMSO, the solvent is more capable of stabilizing the cation than the anion, and the anion tends to become reactive because it is relatively unstabilized. The addition of #"HMPA"# (another aprotic, dipolar solvent) also tends to separate anion from cation.

So, synthetic chemists, usually make a choice, between solubility and activity. What works, works, even tho they might know that it does work until after they have done the experiment.