Question

Give the structures of the major organic products you would expect from reaction of \(m\) -toluidine \((m-\) methylaniline \()\) with the following reagents: (a) \(\mathrm{Br}_{2}\) (1 equivalent) (b) \(\mathrm{CH}_{3} \mathrm{I}\) (excess) (c) \(\mathrm{CH}_{3} \mathrm{COCl}\) in pyridine (d) The product of (c), then \(\mathrm{HSO}_{3} \mathrm{Cl}\)

Short answer

(a) 4-bromo-3-methylaniline (b) N,N,N-trimethyl-3-methylanilinium iodide (c) N-(3-methylphenyl)acetamide (d) N-(3-methylphenyl)sulfonylacetamide

Step-by-step solution

Understanding m-Toluidine

The starting compound is m-toluidine, which is a derivative of aniline where a methyl group is para to the amino group on the benzene ring. It is important to visualize it to predict the outcomes of the reactions.

Reaction with Br2 (1 equivalent)

Aniline derivatives react with bromine via electrophilic aromatic substitution. The presence of the amino group directs substitution to the ortho and para positions relative to it. In m-toluidine, bromination occurs at the position para to the NH2 group because the meta position is occupied by the methyl group. Therefore, the major product is 4-bromo-3-methylaniline.

Reaction with CH3I (Excess)

Reaction with excess CH3I will lead to methylation of the nitrogen atom. The result is the formation of a quaternary ammonium salt. In this case, the expected product is N,N,N-trimethyl-3-methylanilinium iodide.

Reaction with CH3COCl in Pyridine

The reaction of m-toluidine with CH3COCl in the presence of pyridine will lead to acylation of the amino group. This yields N-(3-methylphenyl)acetamide, where the acyl group is added to the nitrogen atom.

Sulfonylation with HSO3Cl

The acylated m-toluidine (product from Step 4) reacts with HSO3Cl (sulfonyl chloride) leading to sulfonylation on the acetamide nitrogen, producing N-(3-methylphenyl)sulfonylacetamide.

Key concepts

Electrophilic Aromatic Substitution

One of the most common reactions for aromatic compounds, such as m-toluidine, is electrophilic aromatic substitution (EAS). In this process, the aromatic ring itself acts as a nucleophile, reacting with an electrophile and substituting one of its hydrogen atoms. When applying bromine to m-toluidine, the amino group's presence as a strong electron-donating group profoundly affects the substitution pattern. The amino group directs incoming electrophiles to the ortho and para positions relative to itself. However, in m-toluidine, the para position, which is one of the optimal sites for substitution, is already taken by the methyl group. Therefore, bromination of m-toluidine predominantly yields 4-bromo-3-methylaniline.

• Anilines like m-toluidine are known to enhance electrophilic substitution due to their electron-rich benzene ring.
• The amount of bromine used can affect the product's orientation and regioselectivity.

Quaternary Ammonium Salt

Quaternary ammonium salts are a unique class of compounds formed when an amine is alkylated until it has four alkyl groups attached to the nitrogen atom. The nitrogen atom in such structures carries a positive charge, making the compound a salt. In the case of m-toluidine, when reacted with an excess of methyl iodide (\(CH_{3}I\)), the nitrogen atom undergoes successive methylations. The final product is a quaternary ammonium salt known as N,N,N-trimethyl-3-methylanilinium iodide.

• The process of methylation transforms the amino group into a positively charged quaternary ammonium center.
• This reaction is typical for tertiary amines and results in versatile compounds with applications ranging from surfactants to bactericidal agents.

Acylation

Acylation is a key reaction in organic chemistry, where an acyl group is introduced into a molecule, often making it less reactive towards certain substitutions. In the presence of an agent like acetic anhydride or an acyl chloride, and usually in the presence of a base like pyridine, amines such as the amino group in m-toluidine undergo acylation. Specifically, reacting m-toluidine with acetic chloride in pyridine forms N-(3-methylphenyl)acetamide.

• Acylation typically uses a catalyst or base to neutralize the resulting hydrochloric acid.
• The introduction of an acyl group provides enhanced stability by reducing electron density on the nitrogen.

Sulfonylation

Sulfonylation involves introducing a sulfonyl group into a compound, and it's widely used in modifying amines and other nucleophilic centers. Once the m-toluidine is acylated, it reacts with sulfonyl chloride (\(HSO_{3}Cl\)) to form a sulfonamide derivative. During this process, the acetamide nitrogen acquires a sulfonyl group, transforming N-(3-methylphenyl)acetamide into N-(3-methylphenyl)sulfonylacetamide.

• Sulfonylation is valuable in organic synthesis, adding a protective group or changing solubility properties.
• This reaction results in compounds that contain both acyl and sulfonyl groups, which are significant in pharmaceuticals and agrochemicals.