Question

Synthesize n-pentylamine from any alcohol using the process of (a) Hofmann degradation (b) nitrile reduction (c) reductive amination

Short answer

To synthesize n-pentylamine (\(C_{5}H_{11}N\)) using the given processes, perform the following steps: (a) Hofmann degradation: 1. Convert n-hexanol (\(C_{6}H_{13}OH\)) to n-hexylamine using hydrochloric acid. 2. Perform Hofmann degradation by reacting n-hexylamine with hypobromous acid and aqueous sodium hydroxide to obtain n-pentylamine. (b) Nitrile reduction: 1. Convert pentyl alcohol (\(C_{5}H_{11}OH\)) to pentanenitrile via pentyl chloride, using thionyl chloride and potassium cyanide. 2. Reduce pentanenitrile to n-pentylamine using lithium aluminum hydride. (c) Reductive amination: 1. Convert pentyl alcohol to pentanal with pyridinium chlorochromate (PCC). 2. Perform reductive amination by reacting pentanal with ammonium chloride and sodium cyanoborohydride to form n-pentylamine.

Step-by-step solution

Convert n-hexanol to n-hexylamine

To do this, react n-hexanol with hydrochloric acid to form n-hexyl chloride: \[C_{6}H_{13}OH + HCl \rightarrow C_{6}H_{13}Cl + H_{2}O\]

Convert n-hexylamine to n-pentylamine using Hofmann degradation

React n-hexylamine with hypobromous acid (HOBr) and aqueous sodium hydroxide (NaOH) to yield n-pentylamine: \[C_{6}H_{13}NH_{2} + 2NaOH + Br_{2} \rightarrow C_{5}H_{11}NH_{2} + 2NaBr + H_{2}O\] (b) Nitrile reduction: To synthesize n-pentylamine using nitrile reduction, we can start with pentyl alcohol (\(C_{5}H_{11}OH\)).

Convert pentyl alcohol to pentanenitrile

First, react pentyl alcohol with thionyl chloride (SOCl₂) to form pentyl chloride, and then react with potassium cyanide (KCN) to form pentanenitrile: \[C_{5}H_{11}OH + SOCl_{2} \rightarrow C_{5}H_{11}Cl + SO_{2} + HCl\] \[C_{5}H_{11}Cl + KCN \rightarrow C_{5}H_{11}CN + KCl\]

Reduction of nitrile to amine

Reduce pentanenitrile to n-pentylamine using lithium aluminum hydride (LiAlH₄): \[C_{5}H_{11}CN + 4LiAlH_{4} \rightarrow C_{5}H_{11}NH_{2} + 4LiAlH_{3}\] (c) Reductive amination: In this process, we will use pentanal (\(C_{5}H_{10}O\)) which can be synthesized from pentyl alcohol.

Convert pentyl alcohol to pentanal

First, react pentyl alcohol with pyridinium chlorochromate (PCC) to form pentanal: \[C_{5}H_{11}OH + PCC \rightarrow C_{5}H_{10}O + \text{reduced PCC}\]

Reductive amination of pentanal

React pentanal with ammonium chloride (\(NH_{4}Cl\)) and sodium cyanoborohydride (\(NaBH_{3}CN\)) to form n-pentylamine: \[C_{5}H_{10}O + NH_{4}Cl + NaBH_{3}CN \rightarrow C_{5}H_{11}NH_{2} + NaCl + H_{2}O\]

Key concepts

Hofmann Degradation

The Hofmann degradation is an essential reaction in organic chemistry, especially for transforming primary amides into primary amines. This reaction proves useful when synthesizing smaller amines from larger molecules. In this context, n-hexylamine undergoes Hofmann degradation to become n-pentylamine. The key reagents used in this transformation include hypobromous acid (HOBr) and aqueous sodium hydroxide (NaOH). This leads to the removal of the amide's first carbon, effectively shortening the carbon chain by one unit. Ultimately, this degradation results in the formation of a primary amine through the loss of carbon dioxide and rearrangement of remaining atoms.

• The reaction is useful for creating smaller amines from longer carbon chains.
• Involves the use of halogenation and a base.
• Converts the amide group into an amine through decarboxylation.

Nitrile Reduction

The nitrile reduction process involves converting a nitrile group into an amine. This reaction is highly efficient for transforming nitriles into their respective amines due to the presence of reagents such as lithium aluminum hydride (LiAlH₄). To make n-pentylamine, pentanenitrile is used as the starting material. Initially, pentanol is converted to pentanenitrile through reactions with thionyl chloride and potassium cyanide. Following this, pentanenitrile is reduced, effectively adding hydrogen across the carbon-nitrogen triple bond. This reduction produces n-pentylamine as the nitrile group transforms into a primary amine group.

• Highly efficient for forming primary amines from nitriles.
• Involves strong reducing agents like LiAlH₄.
• A key step is the transformation of the carbon triple bond to a single bond.

Reductive Amination

Reductive amination is another vital methodology in synthesizing amines, particularly in converting carbonyl compounds into amines. This process entails reacting an aldehyde or ketone with an amine in the presence of a reducing agent. For the conversion of pentanal into n-pentylamine, an important stage is the formation of an imine intermediate, which is then reduced to an amine with agents like sodium cyanoborohydride (NaBH₃CN). The reaction starts with pentanal, synthesized from pentanol, in reaction with ammonium chloride (NH₄Cl). This method is advantageous due to its simplicity and high yields when producing primary amines.

• Widely used to synthesize different types of amines from carbonyl compounds.
• Requires formation and reduction of an imine intermediate.
• Often uses sodium cyanoborohydride as a reducing agent.

Organic Chemistry Synthesis

Organic chemistry synthesis is a broad and fundamental process needed to build complex molecules from simpler substances. In the context of n-pentylamine synthesis, various organic reactions are utilized, each with distinct mechanisms and outcomes. The goal in synthesis is to lead to the intended product with highest selectivity and efficiency, often involving multiple stepwise transformations. From alcohol conversion to halides, and through amides and nitriles, each step requires careful selection of reagents and conditions. These transformations highlight the versatility and complexity inherent in organic synthesis.

• Series of reactions aimed at creating specific molecular structures.
• Emphasizes selectivity and efficiency in product formation.
• Depends upon the strategic use of reagents and conditions for success.

Alcohol Conversion

Alcohol conversion refers to the transformation of alcohol compounds into various other functional groups, each of which could serve as a building block in more complex synthesis processes. For n-pentylamine, alcohols like n-pentanol can be converted into chlorides, which subsequently become part of further chemistry such as nitrile formation. The initial step often involves reacting with reagents like thionyl chloride (SOCl₂) to convert the alcohol to an alkyl chloride, opening up paths to further chemical transformations. Alcohol conversions are key to versatility in synthesis, making them valuable for creating a range of chemical species.

• Enables transformation of alcohols into more reactive species.
• Facilitates subsequent reactions in synthetic pathways.
• Thionyl chloride is often used for creating acid chlorides.