Question

How would you prepare the following substances from pentanoic acid? (a) Pentanamide (b) Butylamine (c) Pentylamine (d) 2-Bromopentanoic acid (e) Hexanenitrile (f) Hexylamine

Short answer

Use chlorination and Hoffman degradation for amines, HVZ for bromination, and convert to nitrile via reaction with cyanide.

Step-by-step solution

Convert Pentanoic Acid to Pentanamide

Pentanamide can be prepared by converting pentanoic acid to its acid chloride using thionyl chloride (SOCl₂). Then react the pentanoyl chloride with ammonium (NH₃) to get pentanamide. Reaction: 1. Pentanoic acid + SOCl₂ → pentanoyl chloride 2. Pentanoyl chloride + NH₃ → pentanamide

Convert Pentanoic Acid to Butylamine

First, use the Hoffman degradation method. Start by preparing the butylamine - this involves converting butanoic acid to its corresponding amine. Then, decarboxylate to achieve butylamine: 1. Convert butanoic acid to butanamide using NH₃, as shown in Step 1-like reaction. 2. Perform Hoffmann degradation on butanamide to get butylamine.

Convert Pentanoic Acid to Pentylamine

Use the same Hoffman degradation process: 1. Convert pentanoic acid to pentanamide. 2. Perform Hoffmann degradation on pentanamide using Br₂ and NaOH to isolate the primary amine, pentylamine.

Convert Pentanoic Acid to 2-Bromopentanoic Acid

For halogenation at the α-position, use the Hell-Volhard-Zelinsky reaction: 1. Treat pentanoic acid with PBr₃ to convert it to an acyl bromide. 2. Then use br₂ to introduce the bromine. 3. Hydrolyze the acyl bromide back to 2-bromopentanoic acid.

Convert Pentanoic Acid to Hexanenitrile

First convert pentanoic acid to pentanoyl chloride using SOCl₂. Then, convert the acyl chloride to a nitrile using sodium cyanide (NaCN): 1. Pentanoic acid + SOCl₂ → pentanoyl chloride 2. Pentanoyl chloride + NaCN → hexanenitrile.

Convert Pentanoic Acid to Hexylamine

Convert pentanoyl chloride to hexanenitrile as described in Step 5 and use the following conversion: 1. Reduce nitrile to amine using LiAlH₄. 2. This reduction gives hexylamine.

Key concepts

Acid Chloride Formation

Acid chloride formation is a crucial step in converting carboxylic acids into more reactive intermediates like acyl chlorides. An acyl chloride is typically synthesized by treating a carboxylic acid with thionyl chloride (\( ext{SOCl}_2 \)). This reaction replaces the hydroxyl group (-OH) of the acid with a chlorine atom, forming an acyl chloride. The general reaction is:

• Carboxylic Acid + \( ext{SOCl}_2 \) → Acyl Chloride + \( ext{SO}_2 \) + \( ext{HCl} \)

This process is appealing due to its simplicity and high yield of acyl chlorides. The use of thionyl chloride is advantageous because the by-products are gases and are easily removed, leaving behind pure acyl chloride.

Hoffman Degradation

The Hoffman degradation is a method to convert amides into primary amines, shortening the carbon chain by one carbon atom. This reaction involves the use of bromine (\( ext{Br}_2 \)) and sodium hydroxide (\( ext{NaOH} \)):

• Amide + Br₂ + NaOH → Primary Amine + NaBr + \( ext{Na}_2 ext{CO}_3 \) + \( ext{H}_2 ext{O} \)

The mechanism involves the formation of an isocyanate intermediate, which hydrolyzes to give an amine. This reaction is particularly useful for synthesizing primary amines where the removal of the carbonyl group is desired, effectively reducing the carbon length of the original amide by one.

Hell-Volhard-Zelinsky Reaction

The Hell-Volhard-Zelinsky (HVZ) reaction is used to halogenate carboxylic acids at the alpha position. This is especially useful for incorporating halogen atoms into carboxylic acids:

• Start by converting the acid into an acyl halide using \( ext{PBr}_3 \).
• Next, treat the acyl halide with Br₂ to introduce the bromine atom to the alpha position.
• Finally, hydrolyze the acyl bromide back to the carboxylic acid form.

This method is beneficial because it selectively introduces a bromine atom into the alpha position without affecting other parts of the molecule, providing a versatile functional group for further chemical transformations.

Amine Synthesis

Amine synthesis often involves the reduction of derivatives such as nitriles or imines. One common strategy involves the reduction of nitriles to primary amines using agents like lithium aluminum hydride (\( ext{LiAlH}_4 \)). Amine synthesis is important in forming key building blocks for pharmaceuticals and materials:

• Nitrile + \( ext{LiAlH}_4 \) → Primary Amine

This process is highly valued for its ability to generate amines directly and selectively from nitrile precursors, making it a staple reaction in organic synthesis.

Nitrile Reduction

Nitrile reduction transforms nitriles into primary amines, which broadens the utility of nitriles in synthetic chemistry. One prominent method of achieving this uses \( ext{LiAlH}_4 \), a powerful reducing agent:

• Nitrile + \( ext{LiAlH}_4 \) → Primary Amine

The reaction typically proceeds through the formation of an imine intermediate, which is further reduced to give the amine product. This technique is prized for transforming nitriles due to its efficiency, creating straightforward pathways to produce various amine compounds important in synthesis.