Nucleophilic attack on a carbonyl is one of the most important reactions in organic chemistry. Not only is it a good way to turn a carbonyl into an alcohol, it becomes the gateway for that alcohol to interconvert into many other functional groups. That’s why nucleophilic attack on a ketone or aldehyde is very important for you to understand. But let’s move on first. Here are a couple of examples of nucleophilic attack on a carbonyl:
The mechanism is also important understand. It all starts with the nucleophile attacking the carbonyl at the carbon. Attack occurs at this position because there is a partial positive charge on the carbonyl carbon, meaning it is electrophilic. (You can also confirm this by drawing the resonance structure) This forms a tetrahedral intermediate, with a negative charge on the oxygen.
At this point the pi bond has been broken and the intermediate alkoxide is formed. If the carbonyl that was attacked is a ketone or aldehyde, the negative oxygen or alkoxide will pick up a proton during work up and become the alcohol. If an ester or acid halide was attacked, the carbonyl is reformed but we will look at that reaction later.
Remember when doing these type of reactions, there are more than one type of nucleophile that can attack the carbonyl. Lewis acids can also be used as catalysts in this type of reaction to accelerate the formation of product. The Lewis acid acts to draw electron density away from the oxygen which in turn pulls electron density out of the pi bond. This causes the carbon of the carbonyl to become much more electrophilic and therefore much more reactive.
Some common nucleophiles you will see attack a carbonyl are listed below:
- Grignard reagents, such as CH3MgBr, CH3CH2MgCl
- Organolithiums, such as CH3Li, CH3CH2Li
- Alkoxides, such as NaOCH3, and NaOCH2CH3
- Cyano groups, such as NaCN
Dr. Michael Pa
Dr. Michael Pa got a bachelors degree in chemistry from Binghamton University, a masters degree in organic chemistry from the University of Arizona and a Ph.D. in organic chemistry from the University of Arizona. His research focus was on novel pain killers which were more potent than morphine but designed to have fewer side effects. There may even be a patent or two that came out of it. Prior to all of this, he was a chemist at Procter and Gamble. After all of that, he (briefly) worked as a post-doctoral assistant at Syracuse University, working on novel organic light-emitting diodes (OLEDs). In between, he did NOT compete at the 1996 Olympics, make the Atlanta Braves opening day roster, or become the head coach of the Indiana Pacers, as he had intended. #fail During this entire time, he always loved helping students, especially if they were struggling with organic chemistry. In 2006, Dr. Pa founded AceOrganicChem.com in order to make learning organic chemistry fast and easy. 14 years and about 60,000 students later we are still helping students to learn organic chemistry one reaction at a time at https://www.aceorganicchem.com
