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The Nucleophilic addition is an addition reaction in which a nucleophile reacts with an electrophilic carbonyl carbon. As a result, a new sigma bond is made. These types of reactions help in the development of new complex organic chemicals. Most importantly, this reaction holds an important place in organic chemistry because it implements the reorganization of carbonyl into different kinds of functional groups. The various types of nucleophilic and the interrelated reactions help us in the biological synthesis of compounds in the metabolic procedure of living beings.
Normally, nucleophilic addition reactions of carbonyl compounds can be divided into the following three steps:
Electrophilic carbonyl carbon builds a sigma bond with the nucleophile.
The Carbon-oxygen pi bond is subdivided, creating an alkoxide interposed.
Subsequent protonation of the alkoxide generates the alcohol derivatives.
The Reactivity of Carbonyl Compounds
This reactivity is mainly dependent on the immensity of the effective charge on the carbonyl atom. It is also known that the reactivity is higher for the electron-deficient carbon. Groups anchored to the carbonyl carbon are influenced by the reactivity of Carbonyl Compounds towards the Nucleophilic Addition Reaction.
The Aldehydes are more reactive towards nucleophilic addition reactions compared to ketones. Therefore, the primary carbocation formed by ketones is mainly more inclined to nucleophilic attacks, whereas the secondary carbocation of ketones is stabilized by adjoining R groups.
The mechanism of nucleophilic addition reaction:
The steps involved in the mechanism of nucleophilic addition reactions are:
The Nucleophile makes a bond with the electrophilic C=O carbon atom, resulting from rehybridization of the carbonyl carbon from sp2 to sp3. The electrons present in the pi-bond are attracted towards the electronegative oxygen atoms, which, as a result, gives us an intermediate tetrahedral alkoxide.
When an acid is added to make alcohol, the alkoxide is protonated.
The Nucleophiles that are strong, like RMgX (Grignard reagent), RLi, and others are added directly to the C=O bond. Whereas the Nucleophiles that are weak like H2O, ROH, and RNH2, need acid catalysts.
Nucleophilic addition reaction plays a crucial role in organic chemistry. It is a reaction where a chemical compound with an electrophilic reaction reacts with nucleophile double or triple times. This reaction gives an overall effect of substitution.
Types of addition reactions
The Nucleophilic Addition of Water-
It is a chemical reaction in which nucleophilic addition of water to a carbonyl compound is done, which results in a geminal diol. The Nucleophilic Addition of Water reactions are slow under neutral conditions.
The Nucleophilic Addition of Alcohols:
Generally, this reaction takes place in the presence of an acid catalyst. For example, to form hemiacetal, aldehydes and ketones go through a nucleophilic addition reaction with alcohols.
The reactions with Hydrogen Cyanide:
Cyanohydrin Formation
Nucleophilic addition reactions between hydrogen cyanide (HCN) and carbonyl compounds (aldehydes and ketones) form cyanohydrins.
Cyanide (HC≡N) can also be reversibly added to water to form products called cyanohydrins.
RCH=O + H–C≡N → RCH(OH)CN (a cyanohydrin)
Due to the fact that hydrogen cyanide is itself an acid (pKa = 9.25), the addition cannot be acid-catalyzed. Whenever the cyanide anion, C≡N-, is used, a catalytic base must be added. An aldehyde-friendly reaction, cyclic ketones and methyl ketones can form unhindered.
Thus, this reaction is not generally done using hydrogen cyanide (HCN) only because HCN is a hazardous, poisonous gas. Therefore, the solution of sodium or potassium cyanide is mixed with aldehyde or ketone in the water, which consists of a small amount of sulphuric acid. This solution contains not only HNC but also contains some amount of free Cyanide ions.
NH3 and Its Derivatives
NH3 is also referred to as ammonia. Its derivatives are:
The reaction with Primary Amines to form Imines:
Imine derivatives are formed by aldehydes and ketones with Ammonia or 1º- amines, also known as Schiff bases. So, the water is eliminated in the reaction, which is precisely acid-catalyzed and reversible, similar to acetal formation. Therefore, the pH for such reactions, which form imine compounds, should be taken care of and controlled. At low pH, mainly all the amines are tied up as its ammonium is joined with acid, making it non-nucleophilic. Whereas, at a high pH level, there is not enough acid left to protonate in the intermediate to permit the removal of water.
Reversibility of imine forming reactions:
Under acidic conditions, imines can be hydrolyzed back to the corresponding primary amine.
Reactions involving other reagents of the type Y-NH2:
Sometimes, Imines can be problematic to isolate and purify because of their sensitivity to hydrolysis. Accordingly, other Reagents of Y-NH2 have been thoroughly studied and found to give stable and positive products, which is helpful in the characterization of aldehydes and ketones exactly from which it has been made.
Reaction with Secondary Amines to form Enamines
Many aldehydes and ketones react with 2º amines to deliver products that are referred to as enamines. In this, the reaction with water is lost because these are acid-catalyzed. Accordingly, the Enamines can be easily converted back to carbonyl originator through acid-catalyzed hydrolysis.
