The following compound has been found effective in treating pain and inflammation (J. Med. Chem. 2007, 4222). Which sequence correctly ranks each carbonyl group in order of increasing reactivity toward nucleophilic addition?
A) 1

Question

The following compound has been found effective in treating pain and inflammation (J. Med. Chem. 2007, 4222). Which sequence correctly ranks each carbonyl group in order of increasing reactivity toward nucleophilic addition? 
A) 1 < 2 < 3 
B) 2 < 3 < 1 
C) 3 < 1 < 2 
D) 1 < 3 < 2

Quizplus · Accepted Answer

Carbonyl reactivity towards nucleophilic addition is primarily determined by the electron-withdrawing ability of groups attached to the carbonyl carbon. In this compound, carbonyl group 2 has two electron-donating methyl groups attached to the carbon, making it the least reactive towards nucleophilic addition. Carbonyl group 3 has only one electron-donating methyl group attached and a moderately electron-withdrawing amide group, making it more reactive than carbonyl group 2. Carbonyl group 1 has no electron-donating groups attached and a very electron-withdrawing ester group, making it the most reactive towards nucleophilic addition. Therefore, the correct sequence of increasing reactivity is 2 < 3 < 1, which corresponds to option B.

The Following Compound Has Been Found Effective in Treating Pain