Question

29. How propyl amine can be synthesized by Gabriel Synthesis? Write the mechanism of the reaction.

30. How reductive amination methodology can be applied for the synthesis of the potent CNS drug “Amphetamine”?

31. Write note on “Sandmeyer reaction”. Write down the mechanism of formation of p-Bromotoluene from pMethylaniline.

Answer 1

The Gabriel Pthalimide synthesis is used for the synthesis of primary amines from primary alkyl halides. The reason we can only synthesize primary amine is because of the inherent nature of reaction mechanism as it involves a binuclear substitution reaction(SN2) and for a substrate to give SN2 it should be a primary substituent.

Since the important step in the mechanism is a binuclear substitution reaction hence we can only use those primary halides which are good substrates for SN2 reactions.

The mechanism of the reaction is given below .

Mechanism of the reaction :

The reaction involved in Gabriel Pthalimide synthesis is given in the reaction scheme below:

The very first step of reaction mechanism involves the deprotonation of acidic proton available on nitrogen and hence on adding KOH, the OH- ion can easily abstract that proton and the negative charge

ends up being at nitrogen.

Due to the negative charge on Nitrogen it behaves as a very good nucleophile and attacks on the primary alkyl halide leading to a substitution reaction and formation of a intermediate B as shown in the meachanism.

In the second step of the reaction we use hydrazine as a base which attacks at the carbonyl carbon of A and leads to a unstable tetrahedral intermediate B in a reaction similar to nucleophilic attack on carbonyl groups.

The unstable tetrahedral intermediate further decomposes to give product propyl amine and byproduct Pthalimide hydrazide as shown in the mechanism.