Question

How might you prepare pentylamine from the following starting materials? (a) Pentanamide (b) Pentanenitrile (c) 1-Butene (d) Hexanamide (e) 1 -Butanol (f) 5 -Decene (g) Pentanoic acid

Short answer

Use methods like Hofmann rearrangement, reduction of nitriles with LiAlH₄, and via bromination followed by nucleophilic substitution.

Step-by-step solution

Convert Amide to Amine

To prepare pentylamine from pentanamide, perform a Hoffman degradation. Heat the amide with bromine and an aqueous hydroxide base (e.g., NaOH) which will remove the carbonyl group, reducing the carboxamide to an amine, leaving pentylamine.

Nitrile Hydrolysis and Reduction

Begin with pentanenitrile (a nitrile), which must first be reduced to an amine. Use a reducing agent like LiAlH₄ in an ether solution to directly convert the nitrile group to a primary amine, forming pentylamine without an intermediate step.

Hydrobromination and Amine Formation

Convert 1-Butene to 1-bromobutane using HBr in the presence of peroxide (anti-Markovnikov addition). Follow it up with a nucleophilic substitution reaction, where 1-bromobutane undergoes reaction with concentrated NH₃ to yield pentylamine after the addition of 1 carbon through cyanide ion followed by reduction.

Rearrange Amide to Amine

Start with hexanamide and use the Hoffman rearrangement similar to pentanamide. Use bromine in an alkaline solution (commonly NaOH) to eliminate one carbon, converting hexanamide into pentylamine.

Alcohol to Amine Conversion

First, convert 1-butanol to 1-bromobutane through reaction with PBr₃. Subsequently, react this alkyl halide with KCN to form the corresponding nitrile, pentanenitrile, and finally reduce it using LiAlH₄ to achieve pentylamine.

Debromination and Reduction to Amine

Start with 5-Decene by converting it to 5-bromo-pentane using HBr, followed by KCN to form 5-pentyl nitrile. Reduce this nitrile using LiAlH₄ to yield pentylamine.

Acid to Amine Conversion

Convert pentanoic acid to a more reactive acyl chloride with SOCl₂. Follow this by converting it into an amide through ammonia treatment. Finally, use the Hofmann rearrangement to turn this amide into pentylamine.

Key concepts

Amide to Amine Conversion

The conversion of an amide to an amine is a fascinating process in organic chemistry. It’s a transformation that involves the removal of the carbonyl group from the amide molecule. A common method to achieve this conversion is via the Hoffmann degradation. In this process, the amide is treated with bromine and an aqueous solution of hydroxide, such as NaOH. This effectively removes the carbonyl group and results in the formation of an amine. Here are a few key points to make it clearer:

• This method reduces the number of carbon atoms in the chain by one.
• It involves the use of strong reagents, such as bromine and strong bases.
• The procedure is typically carried out under heat to facilitate the reaction.

By using the Hoffmann degradation, substrates like pentanamide can be converted to pentylamine, making it a powerful tool for organic synthesis.

Nitrile Reduction

Nitrile reduction is a vital step in the synthesis of amines, particularly primary amines. When it comes to reducing nitriles to amines, lithium aluminium hydride (LiAlH₄) is often the reagent of choice. This reducing agent is strong enough to break the triple bond in the nitrile group, converting it directly into an amine group. Here's how this works in essence:

• LiAlH₄ acts as a powerful reducing agent to transfer hydrogens to the nitrile carbon.
• Hydrogenation occurs, resulting in the conversion of the cyano group into an amino group.
• Typically, this requires an inert solvent such as an ether to prevent any side reactions.

Thus, by applying this methodology, pentanenitrile can be efficiently reduced to pentylamine without the need for intermediates.

Hofmann Rearrangement

The Hofmann rearrangement is an incredible reaction in organic synthesis, offering a unique way to convert an amide into a primary amine. Unlike merely removing the carbonyl group, this rearrangement accomplishes the transformation through the migration of the carbon adjacent to the nitrogen. Here's what makes it intriguing:

• Involves the treatment of amides with bromine in an alkaline medium like NaOH.
• The reaction causes one fewer carbon atom to be present, resulting in a primary amine.
• The migration of the nitrogen atom along with a shift of the carbon chain is what makes this reaction unique.

This technique can successfully convert compounds such as hexanamide into pentylamine, effectively cutting down carbon count by one. Hofmann rearrangement showcases the strategic manipulation of molecular structures in organic chemistry.

Hydrobromination

Hydrobromination is an essential transformation in organic synthesis, particularly for converting alkenes to alkyl bromides. This process typically involves adding hydrogen bromide (HBr) to an alkene. When carried out in the presence of peroxide, an anti-Markovnikov addition occurs, meaning the bromine is added to the less substituted carbon atom in the alkene, leading to significant product formation. Here’s a breakdown:

• Anti-Markovnikov addition results in the bromine attaching to the less substituted end due to a radical mechanism.
• It is crucial for forming alkyl bromides necessary for further reactions, specifically nucleophilic substitution.
• Used as a precursor step for various functional group transformations in organic synthesis.

Hydrobromination not only creates reactivity in the target molecule by introducing the bromine atom but also paves the path for further chemical reactions, including amine production through nucleophilic substitution.

Nucleophilic Substitution

Nucleophilic substitution is a cornerstone mechanism in organic chemistry and is fundamental for transforming molecules into more complex structures. In particular, this mechanism involves a nucleophile, which donates a pair of electrons to a substrate, displacing a leaving group. This reaction is often used to convert halides into amines or other functional groups. Here's why it's important:

• Utilizes a nucleophile like ammonia (NH₃) to convert alkyl halides into amines upon displacement of the halide ion.
• It can result in the expansion of the carbon chain when utilizing reagents like cyanide ions, which can then be reduced to an amine.
• Essential for diverse organic transformations, allowing the synthesis of complex molecular architectures.

In organic synthesis, nucleophilic substitution reactions are paramount, providing a versatile pathway to replace groups within molecules, leading to a myriad of functionalized products.