Question

Several diamines are building blocks for the synthesis of pharmaceuticals and agrochemicals. Show how both 1,3 -propanediamine and 1,4-butanediamine can be prepared from acrylonitrile.

Short answer

Question: Describe the synthesis of 1,3-propanediamine and 1,4-butanediamine starting from acrylonitrile. Answer: The synthesis of 1,3-propanediamine and 1,4-butanediamine from acrylonitrile can be achieved in two major steps. First, acrylonitrile undergoes hydrolysis to form an intermediate amine called allylamine. To synthesize 1,3-propanediamine, allylamine reacts with 1,3-dibromopropane in the presence of KOH via an SN2 reaction mechanism. For the synthesis of 1,4-butanediamine, allylamine is first reacted with formaldehyde via a Mannich reaction followed by reduction with hydrazine. The resulting intermediate amine then reacts with 1,2-dibromoethane and KOH via an SN2 reaction mechanism to yield 1,4-butanediamine.

Step-by-step solution

Convert Acrylonitrile to an Intermediate Amine

First, we need to convert acrylonitrile (CH_2=CH-C≡N) to an intermediate amine. For this purpose, we can carry out hydrolysis with the reaction of acrylonitrile with water. The reaction is as follows: CH_2=CH-C≡N + H_2O ⟶ CH_2=CH-CH_2-NH_2 The resulting product is allylamine.

Extend the Chain to 1,3-Propanediamine and 1,4-Butanediamine

Now, we need to extend the chain to form the desired diamine molecules. #

2.1: Preparation of 1,3-Propanediamine

To obtain 1,3-propanediamine from allylamine, we'll carry out the reaction with 1,3-dibromopropane in the presence of a base (e.g. potassium hydroxide, KOH). This will occur through an S_N2 reaction mechanism. Here's the reaction: CH_2=CH-CH_2-NH_2 + Br-CH_2-CH_2-CH_2-Br + 2KOH⟶ H_2N-CH_2-CH_2-CH_2-NH_2 + 2KBr + 2H_2O The final product is 1,3-propanediamine. #

2.2: Preparation of 1,4-Butanediamine

To obtain 1,4-butanediamine, we need to first add an extra methylene group to the allylamine. This can be done by reacting allylamine with formaldehyde (HCHO) in the presence of a suitable catalyst (e.g. hydrochloric acid, HCl) through a Mannich reaction. The reaction is as follows: CH_2=CH-CH_2-NH_2 + HCHO ⟶ CH_2=CH-CH_2-NH-CH_2 Now, we need to convert the resulting imino group to an amino group. This can be done by reducing the imino group with hydrazine (N_2H_4). The reaction is: CH_2=CH-CH_2-NH-CH_2 + N_2H_4 ⟶ CH_2=CH-CH_2-NH-CH_2-NH_2 + N_2 Next, we need to react this intermediate amine with 1,2-dibromoethane in the presence of a base (e.g. potassium hydroxide, KOH) through an S_N2 reaction mechanism. The reaction proceeds as follows: CH_2=CH-CH_2-NH-CH_2-NH_2 + Br-CH_2-CH_2-Br + 2KOH ⟶ H_2N-CH_2-CH_2-CH_2-CH_2-NH_2 + 2KBr + 2H_2O The final product is 1,4-butanediamine.

Key concepts

Acrylonitrile Hydrolysis

Acrylonitrile hydrolysis is a crucial initial step in the synthesis of various diamines. This process involves the transformation of acrylonitrile, a compound with the triple bond nitrile group (-C≡N), into an amine group (-NH2). The hydrolysis reaction is executed by introducing water (H2O) into acrylonitrile, which results in the opening of the nitrile group to create the primary amine, allylamine. This reaction is fundamental because it provides the primary amine needed for further chain extension reactions.

Understandably, acrylonitrile, comprising a double bond and a nitrile group, offers reactive sites for such transformations. By undergoing hydrolysis, the nitrile group can be converted into an amine group, providing a stepping stone towards the synthesis of more complex amine structures of pharmaceutical and agricultural importance. Students should recognize that this reaction not only changes the functional group but also preserves the chain length, which is pivotal for subsequent steps in the diamine synthetic pathway.

Allylamine Chain Extension

Once the allylamine is produced, it serves as the platform for chain extension to synthesize the desired diamines. The process of allylamine chain extension involves reactions that add carbon atoms to the existing molecule, effectively increasing its molecular size to form 1,3-propanediamine and 1,4-butanediamine.

For the synthesis of 1,3-propanediamine, allylamine undergoes a reaction with 1,3-dibromopropane, while for 1,4-butanediamine, an additional methylene group (-CH2-) is first introduced via the Mannich reaction with formaldehyde. Following this, the Mannich base is subjected to reduction to convert the imino group to an amino group, and then further extended with 1,2-dibromoethane.

Chain extension is a key concept in organic synthesis allowing for the built-up of more complex molecules from simpler ones. Careful selection of reagents and reaction conditions enables the construction of different chain lengths, which is essential for producing compounds with specific properties and applications.

S_N2 Reaction Mechanism

The S_N2 reaction mechanism stands for 'bimolecular nucleophilic substitution' and plays a pivotal role in the synthesis of diamines from allylamine. It is characterized by a single step wherein the nucleophile attacks the electrophilic carbon, leading to the displacement of a leaving group. This reaction proceeds with a backside attack and involves a transition state where bonds are both being formed and broken simultaneously.

In the contexts of 1,3-propanediamine and 1,4-butanediamine synthesis, the S_N2 mechanism applies when allylamine reacts with dibromoalkanes. The nucleophilic nitrogen from the allylamine aims at the carbon that is bonded to a good leaving group, typically a bromine atom in this case, and displaces it to form a new carbon-nitrogen bond.

Students should understand that the S_N2 reaction is highly dependent on the steric hindrance and the nature of the leaving group. It is favored in less sterically hindered primary halides and proceeds with inversion of stereochemistry. This aspect is crucial when considering the reaction's selectivity and outcome in synthetic sequences.