Question

2. Explain why the proposed scheme below will not work to generate guaifenesin. Note: Assume all reagents are soluble in THF (polar aprotic solvent). HC- OH 1. NaH, THE но. OH А он 2. Нco glycerol guaifenesin 1-chloro-2-methoxybenzene reflux, 1 hour

Answer 1

There are two main reason why the reaction will not work,

1) Starting material glycerol has 3 OH groups, all are equally reactive towards deprotonation by a strong base such as NaH. Therefore other OH groups will form the undesired products.

2) The reaction shown here is a nucleophilic aromatic substitution on the 1-chloro-2-methloxybenzene. Here the due to the presence of methoxy group the electron density in the ring increases specifically at ortho and para position. This creates nucluophilic center at ortho and para position. Therefore, the nucleophilic substitution shown above is not possible.