[Chemistry Class Notes] Nucleophilic Addition Reactions Pdf for Exam

A nucleophilic addition reaction is simply a chemical addition reaction in which a nucleophile creates a sigma bond (σ) with an electron-deficient species. Such reactions are considered to be very important in organic chemistry because they enable the conversion of carbonyl groups into several functional groups. In general, nucleophilic addition reaction of carbonyl compounds take place by the following steps-

1. Electrophilic carbonyl carbon forms a sigma bond with the nucleophile.

2. The carbon-oxygen pi bond is then broken, forming an alkoxide intermediate (the bond pair of electrons is passed to the oxygen atom).

3. The subsequent protonation of the alkoxide results in a derivative of alcohol.

The carbon-oxygen dual bond is specifically attacked by strong nucleophiles to give rise to an alkoxide. However, where weak nucleophiles are used, the carbonyl group must be activated, seeking the help of an acid catalyst for a nucleophilic addition reaction to happen.

 

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Here, the carbonyl group has a coplanar structure, and its carbon is sp₂ hybridized. Although, the attack of the nucleophile on the C=O group results in the breakage of the pi bond. Now, the carbonyl carbon is sp₃ hybridized and forms a sigma bond with the nucleophile. As represented above, the resulting alkoxide intermediate has a tetrahedral geometry.

Why do Carbonyl Compounds Undergo Nucleophilic Addition?

The carbon-oxygen bond is polar in the nucleophilic addition of carbonyl compounds. Owing to the relatively higher electronegativity of the oxygen atom, the electron density becomes higher near the oxygen atom. This results in generating a partial negative charge on the oxygen atom and a partial positive charge on the carbon atom.

 

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Because carbonyl carbon holds a partial positive charge, it behaves like an electrophile. The partial negative charge on the oxygen atom can stabilize by introducing an acidic group. The proton is donated by the acid to the carbonyl oxygen atom and neutralizes the negative charge.

 

Relatively, aldehydes are more reactive to nucleophilic addition reactions compared to ketones. This is because the adjacent R groups stabilize the secondary carbocations formed by the ketones. The primary carbocations produced by aldehydes are less stable than secondary carbocations formed by ketones and are thus more vulnerable to nucleophilic attacks.

Mechanism of Nucleophilic Addition Reaction of Carbonyl Compounds

The general mechanism of nucleophilic addition reaction involves two steps.

Step 1 – Nucleophilic attack on carbonyl

 

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Step 2 – Leaving group is removed

 

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Even though nucleophilic addition to aldehydes and ketones contain a carbonyl, their chemistry is different in a distinct manner because they don’t contain a suitable leaving group. Once the tetrahedral intermediate forms, both aldehydes and ketones cannot reform carbinyl. Due to this, aldehydes and ketones typically undergo nucleophilic additions, but no substitutions.

 

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The relative reactivity of carboxylic acid derivatives to nucleophilic substitution is related to the ability of the electronegative group to activate carbonyl. The more electronegative leaving groups withdraw the electron density from carbonyl, increasing its electrophilicity thereby.

 

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Nucleophilic Addition Reaction of Aldehyde and Ketone

Aldehydes are highly reactive and readily undergo nucleophilic addition reactions compared to ketones. Aldehydes demonstrate many favourable equilibrium constants for addition reactions than ketones due to the electronic and steric effect.

 

Aldehydes present more favorable equilibrium constants for additional reactions than ketones due to electronic and steric results. Concerning the ketones case, two large substituents are contained in the ketone structure, which causes steric hindrance when the nucleophile approaches the carbonyl carbon.

 

After all, aldehydes comprise one substitute, and thus the steric hindrance to the approaching nucleophile is comparatively less. In contrast, electronically aldehydes exhibit better reactivity than ketone. It is because ketones contain two alkyl groups that reduce the carbonyl carbon atoms’ electrophilicity rather than aldehydes.

 

The rate-determining step with regards to the base-catalyzed nucleophilic addition reaction and the acid-catalyzed nucleophilic addition reaction is the step, wherein the nucleophile works on carbonyl carbon.

 

Moreover, the protonation process happens in carbonyl oxygen after a nucleophilic addition step in the case of acid catalysis conditions. The carbocation character of the carbonyl structure increases due to protonation and thus makes it further electrophilic.

Reactions of Grignard Reagents with Aldehydes and Ketones

Grignard reagent has a formula – RMgX. 

 

Where ‘X’ is a halogen, and ‘R’ is an aryl or alkyl (depending on a benzene ring) group. 

 

For instance, we shall take R to be an alkyl group.

 

A typical Grignard reagent might be CH₃CH₂MgBr.

Preparation of a Grignard Reagent

All grignard reagents are made by adding halogenoalkane to little bits of magnesium in a flask with ethoxyethane (called either “diethyl ether” or just “ether”). The flask is fitted with a reflux condenser, and the mixture is warmed in a water bath for 20 – 30 minutes.

 

CH₃CH₂Br + Mg  → ethoxyethane → CH₃CH₂MgBr

 

It is to note that everything must perfectly be dry because Grignard reagents can undergo reactions with water.

 

Any reactions using the Grignard reagent are carried out with a mixture formed from this reaction and we cannot separate it out in any other way.

 

These are the reactions of the double bond carbon-oxygen, and therefore aldehydes and ketones react in just the same way – all these changes are the groups that happen to attach with the carbon-oxygen double bond. All these changes are groups that happen to be attached to the double bond of carbon-oxygen.

 

It’s easier to understand what’s going on when looking closer at the general case (using ‘R’ groups instead of specific groups). And then, slotting in various real groups as and when you need to. Also, the ‘R’ groups can be either hydrogen or alkyl in any combination.

 

The Grignard reagent adds across the carbon-oxygen double bond in the first stage, as seen below.

 

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Then, the dilute acid is added to this to hydrolyze it.

 

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Therefore, alcohol is formed. One of the significant uses of Grignard reagents is the ability to produce complicated alcohols easily.

 

Which type of alcohol you get depends on the carbonyl compound you started with, it means what R and R’ are.

Nucleophilic addition Reaction of Carbonyl Compounds

The carbonyl group in chemistry acts as a site of nucleophilic addition (which is also termed nucleophilic assault) and raises the acidity of the hydrogen atoms which are connected to the alpha carbon. Both of these two effects are in relation to the oxygen’s capacity to incorporate or absorb the negative charge and are totally compatible with the structure of carbonyl groups. Also, the carbonyl compounds reactivity towards the nucleophilic addition reaction is influenced by the groups which are attached to the carbonyl carbon. And the reactivity here is dependent on the magnitude of the positive charge present on the carbonyl atom and is high for the electron-deficient carbon. The functional group such as alkyl prevents the nucleophilic attack and therefore, decreases both the electron deficiency and reactivity.

Examples of Nucleophilic Addition Reaction

A few examples of the nucleophilic addition reaction are stated below:

1. Nucleophilic Addition of Alcohols

Aldehydes and ketones go through the nucleophilic addition reaction with alcohols to give out hemiacetal, which then reacts with another molecule of alcohol to give acetal also known as geminal diethers. Acid catalyst is present to complete the reaction.

RCOR’ + 2 R”OH → RC(OR”)2R’ + H₂O

Example: Acetone (CH₃COCH₃) and ethanol (EtOH)here react with each other to give out 2,2 diethoxy propane ((CH₃)₂C(OEt)₂) and water (H₂O).

CH₃COCH₃ + 2 EtOH → (CH₃)₂C(OEt)₂ + H₂O

2. Nucleophilic Addition of Water

The nucleophilic addition of water with the carbonyl compound like an aldehyde or ketone gives out in a geminal diol (hydrate). This reaction goes usually slow under the neutral conditions. However, this rate can be significantly increased by adding an acid or a base catalyst in it.

RCOR’ + H₂O → RC(OH)₂R’

Example: Acetaldehyde (CH3CHO) here hydrolyzes to propane-2, 2-diol (C₃H₈O₂).

CH₃CHO + H₂O → C₃H₈O₂