Aromatic Amines

• Recall:

• The amino group is a powerful activating group that directs ortho and para

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Reduction of Nitro Compounds

• Catalytic hydrogenation:

• Reduction with finely divided metal powders:

223.11 Synthesis of Amines

Reduction of Nitro Compounds

• LiAlH4 and NaBH4 fail to provide the amine

323.11 Synthesis of Amines

Problems

• Draw the products for the following reactions:

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Reductive Amination

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• Sodium cyanoborohydride, NaBH3CN and sodium triacetoxyborohydride, NaBH(OAc)3, are common choices in the lab for the reduction step

• Formaldehyde can be used to introduce methyl groups

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1023.7 Alkylation and Acylation Reactions of Amines

Problem

• Draw the complete mechanism for the following problem:

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Hofmann and Curtius Rearrangements

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The Hofmann Rearrangement

• Sometimes called the Hofmann hypobromite reaction• Cl2 is sometimes used in place of Br2

• A primary amide is the required starting compound

1323.11 Synthesis of Amines

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The Curtius Rearrangement

• Acyl azides provide access to primary amines via an isocyanate• Concerted reaction

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The Curtius Rearrangement

• The resulting isocyanate can be hydrated in acid or base

• Carbamic acids spontaneously decarboxylate

1723.11 Synthesis of Amines

Hofmann vs. Curtius

• In the Hofmann rearrangement, the isocyanate cannot be isolated as the reaction is carried out in aqueous base

1823.11 Synthesis of Amines

Curtius and Hofmann Rearrangements

• In both of these reactions, the alkyl group migrates with complete retention of configuration

1923.11 Synthesis of Amines

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Problems• Draw the mechanisms for the following rxns

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Acylation of Amines

• Amines can be converted into amides by reaction with acid chlorides, anhydrides, or esters.

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• See section 21.8 for review of these rxns

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