SolutionsThe target molecule
Exercise 1
Identify the functional groups, stereocentres and relationships between groups (1,2; 1,3…) in 4-hydroxy-4-methylpentan-2-one. What reaction does its structure suggest?
It has a ketone and a tertiary alcohol in a 1,3 relationship (the OH carbon is β to the carbonyl) and no stereocentre (C4 carries two methyl groups). The β-hydroxycarbonyl relationship is the fingerprint of an aldol reaction: it is the aldol of acetone, formed with base (barium hydroxide) from two molecules of acetone.
Exercise 2
Ibuprofen contains a carboxylic acid. What limitations does that group impose if a Grignard reagent is involved in the synthesis? Give two ways of solving it.
The acidic proton destroys the organometallic (which is protonated to the alkane), and the carboxylate would consume reagent. Solutions: introduce the carboxyl at the end, for example by carboxylating the Grignard reagent itself with CO2 or by hydrolysing a nitrile; or carry it protected in a form inert to organometallics, such as an oxazoline, and release it later with acid.