Question

The procedure of methylation of amines and thermal decomposition of quaternary ammonium hydroxides was first reported by Hofmann in 1851, but its value as a means of structure determination was not appreciated until 1881 , when he published a report of its use to determine the structure of piperidine. Following are the results obtained by Hofmann. Piperidine 1,4 -Pentadiene (a) Show that these results are consistent with the structure of piperidine (Section 23.1). (b) Propose two additional structural formulas (excluding stereoisomers) for \(\mathrm{C}_{5} \mathrm{H}_{11} \mathrm{~N}\) that are also consistent with the results obtained by Hofmann.

Short answer

Answer: Yes, Hofmann's results for the reaction of piperidine are consistent with the structure of piperidine. Two additional structural formulas for C5H11N that are also consistent with Hofmann's results are 1) a five-membered ring containing four carbon atoms and one nitrogen atom, with a one-carbon side chain connected to the nitrogen atom and 2) a straight-chain primary amine with the nitrogen atom connected to the terminal carbon of a 5-carbon chain, which is n-pentylamine. Both of these alternative structures would also undergo the Hofmann degradation reaction, yielding 1,4-pentadiene as a final product.

Step-by-step solution

Understand Hofmann Degradation reaction

The Hofmann degradation reaction is a process that involves the methylation of amines followed by thermal decomposition of quaternary ammonium hydroxides. This reaction allows for a unique way to determine the structure of an amine by reducing its size while maintaining the structure of the newly formed alkene or alkane component. The reaction mechanism can be summarized as follows: 1. Methylation of the amine: converting primary, secondary, or tertiary amines into their corresponding quaternary ammonium salts by reacting with an excess of methyl iodide (\(\mathrm{CH}_{3} \mathrm{I}\)). 2. Formation of the quaternary ammonium hydroxide: treating the quaternary ammonium salt with silver oxide (\(\mathrm{Ag}_{2} \mathrm{O}\)) yields the corresponding quaternary ammonium hydroxide. 3. Thermal decomposition of the quaternary ammonium hydroxide: upon heating, the quaternary ammonium hydroxide decomposes into an alkene or alkane depending on the initial amine structure, with the release of an amine (usually trimethylamine).

Confirm Hofmann's results for piperidine

First, let's take a look at the structure of piperidine: Piperidine is an N-heterocyclic compound, consisting of a 6-membered ring that contains 5 carbon atoms and one nitrogen atom (\(\mathrm{C}_{5} \mathrm{H}_{11} \mathrm{N}\)). To determine if Hofmann's results are consistent with this structure, we will apply the Hofmann degradation mechanism to piperidine: 1. Methylation: Piperidine is a secondary amine. Its nitrogen has two hydrogens that can be replaced with methyl groups from methyl iodide, forming a quaternary ammonium salt. 2. Formation of quaternary ammonium hydroxide: The salt is then treated with Ag2O to form a quaternary ammonium hydroxide. 3. Thermal decomposition: Upon heating, the quaternary ammonium hydroxide decomposes, and a hydrogen from one carbon adjacent to the nitrogen is lost together with the entire nitrogen atom (now in the form of trimethylamine). This forms a pentadiene molecule (1,4-pentadiene). Since the resulting product from piperidine matches Hofmann's result (1,4-pentadiene), it confirms the consistency of the results with the structure of piperidine.

Propose two additional structures

We need to find two alternative structures for \(\mathrm{C}_{5} \mathrm{H}_{11} \mathrm{N}\) that can also yield 1,4-pentadiene upon Hofmann degradation. One possible approach is to consider the nitrogen atom occupying different positions within an aliphatic chain or in a different ring structure. Alternative structure 1: A five-membered ring containing four carbon atoms and one nitrogen atom, with a one-carbon side chain connected to the nitrogen atom. Following the Hofmann degradation mechanism, the resulting compound would be 1,4-pentadiene. Alternative structure 2: A straight-chain primary amine with the nitrogen atom connected to the terminal carbon of a 5-carbon chain. In this case, the amine would be n-pentylamine. Following the Hofmann degradation mechanism, this would yield an alkane (pentane) after the initial steps, however, during the decomposition step, one carbon is lost as methane, leaving 1,4-pentadiene. Both of these alternative structures for \(\mathrm{C}_{5} \mathrm{H}_{11} \mathrm{N}\) would also undergo the Hofmann degradation reaction, yielding 1,4-pentadiene as a final product.

Key concepts

Organic Chemistry Reaction Mechanisms

In organic chemistry, reactions are described step-by-step to show how one molecule is transformed into another. These steps involve movement of electrons and formation or breakage of bonds.

One classic example is the Hofmann Degradation, a multistep process that converts amines into alkenes through a series of specific reactions. These include methylation, formation of a quaternary ammonium hydroxide, and thermal decomposition. Understanding the nuances of electron movements and predicting possible products are crucial skills in organic chemistry.

By analyzing the mechanism, students can predict the outcomes for different amines and how changes in structure can impact the resulting alkene.

• Methylation involves nucleophilic substitution reactions where an amine nitrogen attacks an electrophilic methyl group from methyl iodide.
• Quaternary ammonium hydroxide formation is an example of a salt reacting with a strong base to give a less stable species prone to decomposition.
• Thermal decomposition highlights how applying heat induces bond breakage and the formation of new molecules like alkenes or alkanes.

Nitrogen Heterocycles

Nitrogen heterocycles are organic compounds featuring rings that contain nitrogen as well as carbon atoms. Piperidine, for example, is a six-membered ring with five carbons and one nitrogen atom.

These structures are of interest because the presence of heteroatoms like nitrogen can impart unique chemical properties to the molecule, which are essential in pharmaceuticals and materials science.

• The nitrogen's lone pair can participate in chemical reactions, making heterocycles reactive sites in organic synthesis.
• In Hofmann degradation, the position of the nitrogen within the ring can determine the final alkene structure after the reaction.

Understanding the behavior of nitrogen heterocycles under reaction conditions helps in designing synthetic pathways and in the determination of structural isomers.

Amine Structure Determination

Determining the structure of an amine can be complex due to isomerism, where compounds with the same formula have different structures. The Hofmann Degradation provides chemists with a tool for inferring the structure of amines.

By converting amines into smaller, often simpler molecules, the process reveals information about the original amine's structure.

• In the case of piperidine, the degradation yields 1,4-pentadiene, confirming its specific ring layout.
• Analysis of the final products allows chemists to backtrack and deduce the amine's original structure. This is a key principle in structural organic chemistry.

Structure determination methods like this are foundational for pharmaceutical design and material science, where compound identification is critical.

Alkene Formation

Alkene formation is a common goal in organic synthesis due to their versatility as chemical intermediates. In the context of the Hofmann Degradation, alkenes are produced through the elimination of a nitrogen group from a quaternary ammonium hydroxide, followed by a beta-hydrogen.

The type of alkene formed is indicative of the starting material's structure.

• If we start with piperidine, the resultant alkene is 1,4-pentadiene.
• This selectivity in alkene formation is a direct result of the amine's initial structure and the decomposition process.

Mastery of such transformations is important for creating complex molecules in both the laboratory and industry.