Question

Phenacetin, a substance formerly used in over-the-counter headache remedies, has the formula \(\mathrm{C}_{10} \mathrm{H}_{13} \mathrm{NO}_{2}\). Phenacetin is neutral and does not dissolve in either acid or base. When warmed with aqueous \(\mathrm{NaOH},\) phenacetin yields an amine, \(\mathrm{C}_{8} \mathrm{H}_{11} \mathrm{NO},\) whose \({ }^{1} \mathrm{H}\) NMR spectrum is shown. When heated with HI, the amine is cleaved to an aminophenol, \(\mathrm{C}_{6} \mathrm{H}_{7} \mathrm{NO} .\) What is the structure of phenacetin, and what are the structures of the amine and the aminophenol?

Short answer

Phenacetin is N-(4-ethoxyphenyl)acetamide. The amine is para-ethoxyaniline; the aminophenol is 4-aminophenol.

Step-by-step solution

Analyze Phenacetin Formula

Phenacetin has the chemical formula \( \mathrm{C}_{10} \mathrm{H}_{13} \mathrm{NO}_{2} \). This suggests a potential for aromatic character due to the carbon count and lack of acid or base solubility, which might imply stable aromatic rings.

Reaction with NaOH

Phenacetin is warmed with aqueous \( \mathrm{NaOH} \), yielding an amine with the formula \( \mathrm{C}_{8} \mathrm{H}_{11} \mathrm{NO} \). This indicates the removal of two carbons likely from a small aliphatic chain, hinting that phenacetin's structure included an ethyl group or similar moiety.

Analyze Aminophenol Formation

When the amine is heated with HI, it cleaves to form an aminophenol, \( \mathrm{C}_{6} \mathrm{H}_{7} \mathrm{NO} \). This structure is indicative of a benzene ring with an amine \( (\mathrm{NH}_2) \) and hydroxyl \( (\mathrm{OH}) \) group attached.

Determine Phenacetin Structure

Because phenacetin yields an amine and involves deconstruction to an aminophenol, this suggests it initially includes an acetamide structure. An ethoxide group is merged into an amide, giving the structure: N-(4-ethoxyphenyl) acetamide.

Construct Structures of Products

For the amine \( \mathrm{C}_{8} \mathrm{H}_{11} \mathrm{NO} \), one possible structure is para-ethoxyaniline. For the aminophenol \( \mathrm{C}_{6} \mathrm{H}_{7} \mathrm{NO} \), potential structures are 4-aminophenol, which fits the molecular formula after HI cleavage.

Key concepts

Aromatic Character

Aromatic compounds contain ring structures with delocalized electrons, which make them especially stable. In the context of phenacetin, its chemical formula \( \mathrm{C}_{10} \mathrm{H}_{13} \mathrm{NO}_{2} \) hints at an aromatic character. This stability can be attributed to the presence of a benzene ring—a six-carbon ring with alternating double bonds, making it aromatic.

Aromatic rings do not dissolve in acids or bases easily, explaining why phenacetin remains neutral and stable in those solutions. This intrinsic stability of the benzene ring is an essential feature when deducing the overall structure of phenacetin. Observing how the molecule reacts with other chemicals also provides clues to its aromatic nature.

Acetanilide Derivatives

Derivatives of acetanilide include structures where the main amide moiety is present. In phenacetin's case, its structure is classified as an acetanilide derivative, notably N-(4-ethoxyphenyl) acetamide.

The fundamental framework of these derivatives consists of an aromatic ring—often a phenyl group—attached to an amide. When analyzing a potential acetanilide derivative like phenacetin, understanding this basic arrangement helps in piecing its structure. These compounds often display unique reactivity patterns too, especially when interacting with strong bases or acids, as demonstrated by the reaction to form an amine on treating phenacetin with NaOH.

Aminophenol Synthesis

Aminophenol synthesis is an integral step in understanding the transformation of phenacetin. When phenacetin is treated with HI, it cleaves to form an aminophenol, \( \mathrm{C}_{6} \mathrm{H}_{7} \mathrm{NO} \).

This molecule consists mainly of a benzene ring with an amine \( (\mathrm{NH}_2) \) and hydroxyl \( (\mathrm{OH}) \) group. The cleavage action of HI effectively removes the alkyl moiety from the phenacetin structure, leaving the benzene core intact. This structural transformation is crucial for understanding molecular rearrangements and potential synthetic paths for creating similar molecules.

NMR Spectroscopy

Nuclear Magnetic Resonance (NMR) Spectroscopy is a valuable tool in identifying molecular structures, especially when analyzing compounds like phenacetin and its derivatives. It helps in observing the \( {}^1\mathrm{H} \) NMR spectra of amines derived from phenacetin, providing insights into the electronic environment of the hydrogen atoms.

For instance, in phenacetin, NMR can help determine the locations of the different functional groups by identifying the chemical shifts related to hydrogen atoms in aromatic versus aliphatic environments. Recognizing these patterns aids scientists in determining the precise structure, confirming suspicions about aromaticity and other chemical features.

Ester Hydrolysis

Ester hydrolysis involves the breaking of an ester bond, typically with the aid of a base like \( \mathrm{NaOH} \). Although phenacetin itself is primarily an amide, observing similar hydrolysis reactions helps understand the process of its structural breakdown.

During this reaction, an ester bond would be hydrolyzed, leading to the cleavage of side chains and generating an amine structure. This breakdown is likely similar to the hydrolysis of the group attached to the benzene ring in phenacetin. Understanding ester hydrolysis further aids in unraveling complex transformations and fitting into a broader chemical context, such as the conversion of acetanilide derivatives into more simplified aromatic amines.