Nucleophilic Addition to >C=O Group

This article aims to provide easy-to-understand notes on nucleophilic addition reactions. Here, the focus will be on the nucleophilic addition reaction of carbonyl compounds. We will be studying why ketones and aldehydes go through nucleophilic addition reactions while the alkene groups go through electrophilic addition reactions, as well as the various attacks by reagents for nucleophilic addition to >C=O group. 

Concepts of Nucleophilic Addition Reaction.

Meaning:

• The chemical addition reaction where a nucleophile forms a sigma bond with an electron-deficient species is a Nucleophilic addition reaction.

They can convert carbonyl groups into various functional groups, so they are considered important reactions in Organic Chemistry.

Mechanism: 

• A carbonyl carbon shows sp2 hybridisation, together forming a coplanar structure.

• A nucleophile attacks the polar carbonyl group’s electrophilic carbon atom on the plane of sp2 hybridised orbitals of carbonyl carbon from an approximately perpendicular direction.
• The carbon now shows sp3 hybridisation and produces a tetrahedral alkoxide intermediate.
• This intermediate takes a proton from the reaction medium, giving it a neutral electrical product.
• The net result of the reaction is the addition of Nu- and H+ across the carbon-oxygen double bond.

Reactivity:

• Unlike alkenes that go through electrophilic addition reactions, ketones and aldehydes go through a nucleophilic addition reaction.
• This is because Ketones and Aldehydes show polar nature. 
• In comparison to Ketones, Aldehydes are more reactive and easily undergo nucleophilic addition reactions due to electronic and steric effects.
• As a result, aldehydes provide more favourable equilibrium constants than ketones for addition reactions.
• In ketones, due to the two large substituents, a phenomenon of steric hindrance occurs when a nucleophile tries to approach the carbonyl group. In comparison, aldehydes have only a single such substituent.
• The presence of the two alkyl groups in ketones reduces the electrophilicity of the carbonyl carbon more effectively in comparison to aldehydes. Hence, aldehydes have higher reactivity to nucleophilic addition reactions than ketones.

Nucleophilic addition to >C=O group

The nucleophilic addition to a carbonyl group, i.e., a double-bonded carbon and oxygen atom, is in the following ways –

Nucleophilic attack by hydride:

• Hydride can be added to a carbonyl group with the help of compounds that contain nucleophilic hydrogen atoms.
• The chemical reaction of hydride addition is called a reduction reaction.
• An example of such a compound is sodium borohydride.
• In this chemical reaction, the carbonyl group behaves like an electrophile.
• Single pair of electrons is transferred to the carbon atom of the >C=O group from one of the B–H bonds.
• This reaction can be considered as a form of ‘hydride transfer’.

Formation of Cyanohydrin:

• Cyanohydrin is formed due to the attack of cyanide on either one of them or both of them – ketones and aldehydes – in the presence of an acidic catalyst.
• This acidic catalyst leads to the protonation of the resulting alkoxide, yielding the hydroxyl group.
• Cyanide contains C and N atoms with sp hybridization.
• Its HOMO is a sp orbital on carbon.
• This reaction is a typical nucleophilic addition reaction to a >C=O, i.e., carbonyl group.
• The electron pair from the HOMO of the cyanide moves to the C=O π* orbital, and electrons from the C=O π orbital move towards the oxygen atom.

Formation of Hemiacetal:

• We know that water is added to some carbonyl groups. As a result, it is unfathomable that alcohol can be added too.
• The product formed from these reactions of alcohol and carbonyl groups is known as hemiacetal. This is because it’s almost halfway to an acetal functional group.
• The overall consumption of ethanol is nil in all of the protonation or deprotonation steps. The order of these steps is not important to the reaction.
• The important step is the nucleophilic addition step.

Attack by Organometallics:

• Organometallics are very powerful nucleophiles that attack the carbonyl group to give out alcohols and form new C–C bonds.
• Metals such as Lithium (Li) and Magnesium (Mg) are highly electropositive in nature.
• The Li–C bond in organolithium or Mg–C bond in organomagnesium reagents is highly polarised towards the carbon atoms.
• The reactions of organometallic reagents with the carbonyl group from these two classes are one of the most important ways of the formation of C–C bonds.

Attack by Grignard reagent:

• The reaction from the Grignard reagent is similar to that of organolithium reagents.
• In this nucleophilic addition reaction, methyl magnesium bromide is made to react with ethanal.
• The metal cation again coordinates with the alkoxide, followed by the protonation of oxygen anion (O-) with water.

Attack by Organolithium reagent:

• In this nucleophilic addition reaction, methyllithium is made to react with an aldehyde.
• First, MeLi reacts with ethanal to form alkoxide. The metal atom coordinates with the negatively charged oxygen atom.
• Then water is added to protonate the oxygen atom.

Conclusion

With this article students have been introduced to the concepts of nucleophilic addition reaction, the mechanism of nucleophilic addition reaction, and nucleophilic addition reaction of carbonyl compounds in an easy, precise, and concise manner. They have come to know the reasons as to why aldehydes and ketones go through nucleophilic addition reaction though alkene groups go through electrophilic addition reaction as well as the various attacks by different reagents like hydride, cyanohydrin, Grignard reagent, etc. for the purpose of nucleophilic addition to >C=O group.