Teaching workshop and taking “Organic with the Boss” has brought back all kinds of old-school sophomore organic memories this semester, including the often perplexing role of solvent in reactivity. The thing at once annoying and intriguing about solvent effects is that spotting them requires a very keen sense of the chemistry of the system at hand. Solvent-reagent interactions come in a variety of forms, and often manifest themselves in weird or unfamiliar ways…something first-year organic students often have a hard time accepting.
One interesting example of solvent effects can be seen when looking at the nucleophilicity of the halides in protic solvents: although their basicity decreases from F to I, their nucleophilicity shows exactly the opposite trend. Naturally, an example featuring this apparent paradox appeared on the problem set today, right after I had just told the kids that nucleophilicity generally parallels basicity. The culprit is the protic solvent: the smaller, more basic halides hydrogen bond more strongly with the solvent than the heavier halides. This hydrogen bonding effectively makes the smaller halides heavier and decreases their nucleophilicity. Not surprisingly, gas phase studies showed that the parallel between basicity and nucleophilicity is restored for the bare halide ions: fluoride is the strongest nucleophile and iodide the weakest in the gas phase.