Amines in Organic Chemistry

• Trimethylaminuria is a rare genetic disorder where the body cannot produce the enzyme to oxidize trimethylamine, resulting in a fish-like body odor. • Trimethylamine is a compound produced from trimethylamine oxide by enzymes and bacteria, and is used as a marker of freshness in fish. • Amines are important in biochemistry, medicine, and agriculture, and are involved in various reactions. • There are two naming systems for amines: common names and IUPAC names. • Primary amines have one alkyl or aryl group attached to the nitrogen, secondary amines have two, and tertiary amines have three. • The NH2 group is low priority in IUPAC nomenclature, often seen as a prefix "amino" when there are higher priority functional groups. • Diamines are used as monomers to prepare polymers like nylon and have a strong smell. • Amines have a trigonal pyramidal geometry, with the nitrogen atom being sp3 hybridized. • Amines are weak bases, with the lone pair of electrons on the nitrogen accepting a proton to form a conjugate acid (ammonium ion). • The pKa of the ammonium ion determines the basicity of the amine, with lower pKa values indicating higher acidity. • Substituting additional alkyl groups can increase the basicity of an amine, as they are electron-donating and help stabilize the positive charge. • Resonance can also affect the basicity of amines, such as in aniline, which is a weaker base than alkyl amines. • Nitrogen-containing heterocycles can be aromatic or non-aromatic, with aromatic ones being weaker bases due to sp2 hybridization. • Pyridine is a useful molecule in the lab, used as a precursor to produce herbicides, insecticides, and antiseptics, but has a strong, unpleasant smell. • Amines can be synthesized using nucleophilic substitution reactions and reductions, but may require additional steps to prevent over-alkylation or explosive reactions. • The Gabriel synthesis is a method that uses thalamide to add nitrogen and provides a built-in amine protecting group.- Primary amines can be obtained by reacting a compound with hydrazine.

• Reducing a nitrile group with a haloalkane can also produce a primary amine with a bonus carbon atom.
• Lithium aluminum hydride can be used to reduce amides to primary amines, and also provides a path to secondary and tertiary amines by making amides with alkyl groups substituting for hydrogen atoms.
• Reacting an ester with a primary or secondary amine can produce an amide, which can then be reduced to a secondary or tertiary amine.
• Reductive amination is a reaction that uses a mild reducing agent to add additional alkyl groups to an amine.
• In reductive amination, a hydride is added to the electrophilic carbon of an iminium ion, allowing customization of the alkyl group attached to the nitrogen.
• Iminium ions play a role in the synthesis of penicillin V, where the lone pair on the nitrogen attacks the carbonyl carbon, and a proton jumps to an acetate ion, forming the iminium ion.
• Various nucleophiles can add to iminium ions, including hydroxide ions, which can grab the hydrogen from the thio group and attach the sulfur to the iminium ion carbon.
• Quaternary ammonium salts can be used as leaving groups, and the Hoffman elimination reaction can be used to produce an alkene, water, and a tertiary amine.
• Enamines are molecules with a carbon-carbon double bond next to an amine, and can be formed by reacting an aldehyde or ketone with a secondary amine.
• Enamines can act as nucleophiles, similar to enolates, and can be used in alkylation and aldol reactions, with advantages over enolates including avoiding over-alkylation.
• Enamines can be used in carbon-carbon bond-forming reactions, and can be hydrolyzed to reform an aldehyde or ketone.