Animated Solution for Chemistry - Organic Chemistry: The total number of amines among the following which can be synthesised by Gabriel synthesis is .........

The Gabriel Phthalimide Synthesis is a cornerstone reaction in organic chemistry, celebrated for its ability to produce pure primary aliphatic amines without the messy over-alkylation often seen in direct ammonolysis. But like any highly specialized tool, it comes with strict operational constraints. Let's dive into the mechanics of this reaction to understand why some molecules are perfect candidates while others fail completely.

At the heart of the Gabriel synthesis is a classic nucleophilic substitution reaction. The process begins with phthalimide, which is treated with a strong base like potassium hydroxide to form the resonance-stabilized phthalimide anion. This bulky, nitrogen-centered nucleophile then seeks out an electrophilic carbon on an alkyl halide ($R-X$).

Because the phthalimide anion is quite large, the substitution must proceed via an $S_{N}2$ mechanism. This means the incoming nucleophile attacks the carbon from the backside, simultaneously kicking out the halide leaving group. For an $S_{N}2$ reaction to be successful, the target carbon must be relatively unhindered. Therefore, the Gabriel synthesis is strictly limited to the preparation of primary ($1^{\circ }$) aliphatic amines.

Let's apply this rule to the molecules presented in our problem:

Option (a): Isobutylamine Isobutylamine is a primary aliphatic amine. Its precursor, isobutyl halide, has the halogen attached to a primary carbon. Despite the branching further down the chain, the reaction center is accessible enough for the phthalimide anion to attack. Thus, it is a valid candidate.

Option (b): Ethylamine Ethylamine is the quintessential primary aliphatic amine. Ethyl halides are highly reactive in $S_{N}2$ reactions due to minimal steric hindrance. This molecule can be synthesized effortlessly using the Gabriel method.

Option (c): Benzylamine Benzylamine (${\text{Ph-CH}}_2{\text{-NH}}_2$) often tricks students because of the prominent benzene ring. However, the nitrogen atom is attached to an $s{p}^3$ hybridized $-{\text{CH}}_2-$ group, not directly to the aromatic ring. This makes it a primary aliphatic amine. Furthermore, benzyl halides are exceptionally reactive towards $S_{N}2$ substitution because the adjacent $\pi$-system of the benzene ring stabilizes the transition state. Benzylamine is an excellent candidate for Gabriel synthesis.

Option (d): Aniline Aniline (${\text{Ph-NH}}_2$) is a primary aromatic amine, meaning the nitrogen is bonded directly to the $s{p}^2$ hybridized carbon of the benzene ring. To synthesize aniline via the Gabriel method, we would need an aryl halide (like chlorobenzene) to undergo an $S_{N}2$ reaction with the phthalimide anion.

This is where the chemistry hits a wall. Aryl halides are notoriously unreactive towards nucleophilic substitution for two main reasons: 1. Resonance Stabilization: The lone pairs on the halogen delocalize into the benzene ring, giving the carbon-halogen bond partial double bond character. This makes the bond incredibly strong and difficult to break. 2. Electronic Repulsion: The benzene ring is a dense cloud of $\pi$-electrons, which strongly repels the incoming negatively charged phthalimide anion.

Because the crucial $S_{N}2$ step cannot occur, aniline cannot be synthesized using the Gabriel phthalimide method.

By carefully analyzing the structural requirements of the $S_{N}2$ mechanism, we can confidently conclude that isobutylamine, ethylamine, and benzylamine can all be synthesized via the Gabriel method. Aniline, being an aromatic amine, cannot. Therefore, the total number of valid amines from the given list is 3.