What is Nucleophilic Addition Reaction?
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-
Electrophilic carbonyl carbon forms a sigma bond with the nucleophile.
The carbon-oxygen pi bond is then broken, forming an alkoxide intermediate (the bond pair of electrons is passed to the oxygen atom).
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
FAQs on Nucleophilic Addition Reactions
1. Explain nucleophilic addition reaction with monohydric alcohols?
Aldehydes and ketones undergo nucleophilic external reactions with monohydric alcohols to create hemiacetals. The acetal is obtained following a further reaction with another molecule of alcohol. Because alcohols are weak nucleophiles, the reaction needs an acid catalyst to activate the carbonyl group towards a nucleophilic attack. The reason being the hemiacetals can undergo hydrolysis to produce reagents (alcohol and carbonyl compounds), the water produced during the reaction needs to be removed. During this reaction, carbonyl oxygen is protonated due to the nucleophilic attack by alcohol. Now, the nucleophilic alcohol is deprotonated to produce the hemiacetal. The same reaction can be repeated to obtain acetal.
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2. Explain the nucleophilic reaction with primary amines.
The reaction between the primary amines and aldehydes or ketones generates imine derivatives along with water. The same can be seen below. Firstly, the nucleophilic nitrogen of the amine attacks carbonyl carbon. The carbon-oxygen double bond is thus broken, and a new sigma bond of carbon-nitrogen is formed. The proton is now being transferred from the amine to the oxygen atom. In the next step of this nucleophilic addition reaction, the OH group is further protonated, and the water is removed.
Now, the carbon atom forms a double bond with the nitrogen that belongs to the amine. This nitrogen is now deprotonated to afford the necessary imine product.
3. Why are nucleophilic addition reactions important?
Nucleophilic addition reactions is an important topic in chemistry so is to understand them. Nucleophilic addition reaction is a chemical addition reaction in which a nucleophile establishes a sigma bond with an electron-deficient molecule and therefore it is known as a nucleophilic addition reaction. These types of reactions are very crucial in the section of organic chemistry as they allow carbonyl groups to be converted into a variety of functional groups also The carbon atoms are partially positive in charge, whereas the oxygen atoms are partially negative and because of steric and electrical factors, aldehydes are frequently more reactive toward nucleophilic replacements rather than ketones.
4. What is the nucleophilic addition reaction's mechanism?
A nucleophilic addition reaction is an addition reaction in organic chemistry in which a chemical molecule having an electrophilic double or triple bond combines with a nucleophile, breaking the double or triple bond or when two or more than two reactants combine together to form a product without losing any atom of the reactant, which is also known as an addition reaction. In compounds with unsaturated C-C bonds, such as double (alkene) and triple (alkyne) bonds, the addition reaction is frequent. Here the weaker π (pi) bond is converted into two new types of σ (sigma) bonds which are both stronger in nature.
5. Which steps are involved in the process of a nucleophilic addition reaction?
As we have learned what nucleophilic addition reaction is, understanding the steps involved in it is also very important. There are three major steps involved in the nucleophilic addition reaction which are stated below:
The first step involved in the generation of the nucleophile, the nucleophile CN- is generated when there is a reaction between the acid and base of NaOH and HCN in the presence of a trace of NaOH. If a trace of NaOH is not used and if the trace of NaCN is used in its place then it will be an easy dissociation to generate CN-.
The second step involves the attack of a nucleophile or nucleophilic attack where the nucleophile attacks the carbonyl carbon to form a bond of carbon-carbon. In the second phase, both the electrons will be transferred to oxygen as the pi bond between carbon and oxygen breaks down which leads to generating an alkyoxide. This process takes more time as it is a slow process.
The third and final step is the Protonation and Regeneration of Catalyst. When the alkyoxide oxygen will attack the reactant which is HCN and extract a proton or H+ from it, it will form a product called cyanohydrin where CN- is regenerated during this process. Also, the third step occurs readily and fast in comparison to the second step which was a slow process.
