Nucleophilic Addition Reaction

Aldehydes and ketones are chemical molecules with a carbonyl group (>C= O). As a result, they are referred to as carbonyl compounds. Because the carbonyl group is common in aldehydes and ketones, their methods of synthesis and characteristics are quite similar. 

Carbonyl molecules are found naturally in plants and animals’ nucleic acid carbs and proteins. They serve a crucial part in metabolic processes that keep life going. They bring scent and flavour to nature and are also found in a variety of medications and textiles. Almonds (benzaldehyde), cinnamon (cinnamaldehyde), vanilla bean (vanillin), camphor (from camphor tree), citronella oil (citronellal), vitamin k, and many other natural ingredients including essential carbonyl compounds.

Carbon atoms are connected to oxygen by a double bond in a carbonyl group, while the remaining two valencies are satisfied by hydrogen atoms or alkyl groups. Carbonyl carbon is connected to a hydrogen atom and an allied group in aldehydes, but to two distinct alkyl groups in ketones. Carbonyl carbon is linked to two hydrogen atoms in formaldehyde. The difference in the structure influences the characteristics, such as how aldehydes are more reactive than ketones in nucleophilic addition processes and how quickly aldehydes oxidize. The carbonyl carbon atom is connected to an alkyl group and a (-OH) group in carboxylic acids. The carbonyl group is found in the chemical substances listed below. 

Structure of Carbonyl Functional group

The carbon of the carbonyl group is sp² hybridised and bound to three additional atoms in aldehydes and ketones. Carbon atoms create three sigma (σ) bonds with bond angles of 120° that are all in the same plane. One sigma bond is established with an oxygen atom, and the other two with hydrogen and/or carbon atoms. To produce the pi (π) bond, the remaining unhybridised 2p orbital carbon coincides with the 2p orbital of oxygen. As a result, carbon and oxygen are connected by a double bond. Two lone pairs of electrons are carried by the oxygen atom. 

Structure of carbonyl group

The carbonyl bond is more powerful. In comparison to the double bond in alkenes, this bond is shorter and more polarised. Because oxygen is more electronegative than carbon, the carbonyl group’s double bond is polar and has a dipole moment. Polarization adds to aldehyde and ketone reactivity. 

Nucleophilic addition Reactions of Aldehydes and Ketones

Mechanism

Oxygen has a greater electronegativity than carbon, because of that, the C = O bond in aldehydes and ketones is polarised.

Electrons are highly attracted to oxygen. The oxygen atom receives a partial negative charge (δ^–), whereas the carbon atom receives a partial positive charge (δ⁺).

This high polarity of carbonyl group is explained on the basis of resonance involving a neutral [Fig 1] and Dipolar [Fig 2] structures.

Nucleophilic addition reactions occur between aldehydes and ketones. A nucleophile, Nu^–, approaches the plane of the carbonyl group from an angle of about 75° degrees along the C = O bond and attaches to an electrophilic carbonyl carbon atom. The hybridised state of the carbonyl carbon atom shifts from sp² to sp³ during this process. The electron pair in the C=O bond changes to carbonyl oxygen, resulting in the formation of a tetrahedral alkoxide ion intermediate. To produce the final product, this tetrahedral intermediate is protonated. As a result, the net result of the addition of Nu^– and H⁺ across the C = O bond is [refer to below image

Mechanism of nucleophilic addition reaction

Aldehydes are more reactive than ketones in nucleophilic addition processes for both steric and electrical reasons. Because aldehyde has just one bulky substituent, a nucleophile can reach the carbonyl carbon more easily than ketones, which have two bulky substituents. The carbonyl carbon in aldehyde is more electrophilic than the carbonyl carbon in ketones. This is due to the +I effect of two bulky substituents in ketones reducing the electrophilicity of carbonyl carbon.

The result of aldehyde attack is less inhibited than the product of ketone attack, especially with a bulky mucleophile (sterric effects). Aromatic aldehydes are less reactive in nucleophilic addition processes than aliphatic aldehydes. This is due to the aromatic ring’s electron-donating resonance effect, which renders carbonyl carbon less electrophilic.

• Addition of Cyanide

Aldehydes and ketones add hydrogen cyanide to give corresponding cyanohydrins. The reaction is reversible and occurs slowly when pure hydrogen cyanide is used  but rapidly when a small amount of base is used to generate the nucleophile CN^–

The mechanism of addition of nucleophile CN^– is given below,

Step 1: A strong nucleophile adds to the carbonyl group (>C = O) to form an intermediate alkoxide.

Step 2: The alkoxide ion formed is protonated by a weak acid to give the addition product. 

[Note: The cyanohydrin formation is reversible. The order of reactivity is Formaldehyde > other aldehydes > Ketones]

For Examples:

Acetaldehyde reacts with Hydrogen cyanide to give acetal cyanohydrin

• Addition of sodium bisulphate

Aldehydes and ketones when treated with saturated aqueous solution of sodium bisulphate give addition products

They are water soluble crystalline solids that are hydroxy sulphonic acid salts. By treating them with weak mineral acids or alkali, they may be readily hydrolyzed back to aldehydes and ketones. As a result, this process is used to separate and purify aldehydes or ketones from other organic molecules. 

• Addition Of Grignard Reagent

An aldehyde or a ketone undergoes nucleophilic addition of grignard reagent in presence of dry ether to form a complex which on acid hydrolysis gives alcohol

Methanal reacts with methyl magnesium iodide in presence of dry ether to give complex which on acid hydrolysis gives ethanol.

Note: Methanal produces primary alcohols containing one more carbon than in grignard reagant.

• Addition of alcohols

Aldehydes and Ketones react with alcohols to form branched acetal and cyclic acetal.

• Branched acetal

Two molecules of alcohol are added to carbonyl group to form acetal by elimination of one water molecule

Step 1: Acid catalysed addition of an alcohol to the carbonyl group n presence of dry hydrogen chloride, to form hemiacetal.

Step 2: In the second half of the mechanism the hemiacetal gets converted to more stable acetal

• Cyclic acetal

Acetal is a geminal dialkoxy compound (an ether). Aldehydes and Ketones react with one equivalent of 1,2 or 1,3 -diols in presence of dry hydrogen chloride to give cyclic acetal.

Acetal and Ketals are rapidly hydrolysed back into aldehydes and Ketones, by the action of dilute mineral acids even at room temperature

• Addition of ammonia and its derivative

Urotropine is formed when formaldehyde interacts with an excess of ammonia to form hexamethylene tetramine. Urotropine is used as an antiseptic for the urinary tract, as well as to treat rheumatism and gout. It is also utilised in the manufacture of polymers and pharmaceuticals. When nitrated, it produces cyclonite, a powerful explosive.

6HCNO  +  4NH₃    ⟶    (CH₂​)₆​N₄​  +  6H₂​O

Hexamethylene tetramine has a cage-like structure composed of three six-membered rings, each in chair conformation. 

Structure of hexamethylene tetramine

Acetaldehyde dissolved in ether reacts with ammonia gas to form solid acetaldehyde ammonía. It loses a water molecule to give an imine which further trimerises to give a heterocyclic compound.

When acetone is boiled with ammonia in slightly acidic medium for long time, diacetone amine is formed. The reactions take place in two steps as follows.

Several ammonia derivatives of the H₂N-Z type react with aldehydes or ketones to form an addition product that loses a water molecule to form imines. The process is reversible and catalysed by acid. Carbonyl oxygen is protonated, making carbonyl carbon more vulnerable to attack by the nucleophile H₂NZ. However, in sufficiently acidic media, the nitrogen atom of the ammonia derivative H₂NZ gets protonated, resulting in the ion H I N+-Z, which is no longer a nucleophile. As a result, the process is aided by low acidity.

Here Z is -R, -Ar, -OH, -NH₂, -NHC₆H₅ etc. The C = O group is transformed into the C = N – Z group. The majority of imines can be hydrolyzed back to aldehydes, ketones, and amines. A Schiff base is a substituted imine. Because these imine derivatives are frequently solids with high melting temperatures, they are employed for the characterization and identification of aldehydes and ketones.

Note: Carboxylic acid has a carbonyl group but does not undergo nucleophilic addition as do aldehyde and ketone. The partial positive charge on the carbonyl carbon atom is lowered as a result of resonance.

Sample Questions

Question 1: What are aldehyde and ketones? How are ketones classified?

Answer: 

Aldehydes are the carbonyl compounds, in which carbonyl group is attached with at-least one -H atom. 

Ketones are the first oxidation products of secondary alcohols. They contain > C = O functional group.

Classification of Ketones

• Simple ketone (similar alkyl groups)
• Mixed ketone (different alkyl groups)

Question 2: Explain aldehydes and ketones undergo nucleophilic reaction and carboxylic acid doesn’t?

Answer:

In carbonyl group (C=O)), oxygen being more electronegative, electrons get slightly shifted towards the oxygen atom. Due to this, the carbon-atom develops a partial positive charge (electron deficient)

Hence the carbon atom in the carbonyl group is readily attacked by a nucleophilic addition reaction.

On the other hand, Carboxylic acid possesses a carbonyl group but, unlike aldehyde and ketone, does not undergo nucleophilic addition. As a result of resonance, the partial positive charge on the carbonyl carbon atom is reduced. 

Question 3: What is the action of the following reagent on formaldehyde

• HCN
• NaHSO₃

Answer:

• HCN

Action of HCN on formaldehyde: Fmaldehyde when reacted with hydroge cyanid gives formaldehyde cyanohydrin

• NaHSO₃

Formaldehyde when reacted with sodium bisulphite gives formaldehyde sodium bisulphite.

Question 4: Why does aldehyde undergo nucleophilic addition reaction more readily than the ketones?

Answer:

The electron-releasing group (+I effect) of the alkyl radicals linked to the carbonyl carbon in ketone makes the carbonyl carbon less positive. This reduces the proclivity of carbonyl carbon to accept the nucleophile. As a result, aldehydes are more easily nucleophilic than ketones.

Question 5: How will you prepare hexamethylene tetramine using an aldehyde, also draw its structure?

Answer:

Using Formaldehyde we can prepare hexamethylene tetramine

Formaldehyde, when reacted with ammonia (NH₃) in ether solution gives hexamethylene tetramine, i.e., urotropine

Question 6: What is the action of CH₃ – MgI on acetaldehyde, give reaction?

Answer:

Acetaldehyde when reacted with CH₃ – MgI in the presence of dry ether, gives Mg – complex, which on hydrolysis with dil. acid gives iso – propyl alcohol

Question 7: Write the structure of carbonyl compound and ammonium derivatives that combine to give the following imine.

Answer:

Carbonyl compound is,

Ammonium derivative is,