Which of the following substrates would react most efficiently in a substitution reaction with sodium cyanide (NaCN)?
(A) 1-iodohexane (B) 1-fluorohexane (C) (R)-2-bromohexane (D) chlorocyclohexane (E) 1-bromo-1-methylcyclohexane
Answer: (A) 1-iodohexaneA
We first must figure out which reaction does the question ask about. The question mentions substitution reaction, thus either SN1 or SN2. We are also given NaCN as the nucleophile. We need to remember that SN1 prefers neutral, weak nucleophiles while SN2 prefers strong, often negatively charged nucleophiles. NaCN is an ionic compound, which we can rewrite as Na+ and CN-. CN- is a strong nucleophile (it has a negative charge). While, NaCN might have looked neutral to begin with, Na was a spectator ion hiding out CN-. Therefore, the reaction in this problem is SN2.
What kind of substrates does an SN2 reaction prefer? Primary substrates (leaving group is attached to a carbon that is attached to only one more carbon). We can thus eliminate choices C, D and E since these are not primary. The different between A and B is the identity of the leaving group (Iodine vs Fluorine). We need to know that for halogens, as the size increases, the halogen becomes a better and better leaving group. Therefore, iodine is a much better group that fluorine.