Amines and Amides

17.1 Bonding Characteristics of Nitrogen Atoms in Organic Compounds

Nitrogen, a Group VA element, possesses five valence electrons and achieves a stable octet by forming three covalent bonds.

17.2 Structure and Classification of Amines

• Amine Definition: Organic compounds derived from ammonia ($NH_3$), where one or more alkyl, cycloalkyl, or aryl groups are bonded to the nitrogen atom.
• Classification of Amines:
  • Primary ($1^o$) amines: one R group attached to the nitrogen.
  • Secondary ($2^o$) amines: two R groups attached to the nitrogen.
  • Tertiary ($3^o$) amines: three R groups attached to the nitrogen.
• Cyclic Amines: These can be either secondary or tertiary. They are also termed heterocyclic compounds and are commonly found in biochemical systems.

17.3 Nomenclature for Amines

• IUPAC Rules for Naming Primary Amines:
  1. Identify the longest carbon chain bonded to the nitrogen atom as the parent chain.
  2. Change the suffix of the corresponding alkane name from -e to -amine.
  3. Number the parent chain starting from the end closest to the nitrogen atom.
  4. Indicate the position of the nitrogen atom's attachment with a number preceding the parent chain name.
  5. Append the identity and location of any substituents to the front of the parent chain name.
• Secondary and Tertiary Amines: Named as N-substituted primary amines.
  • The largest carbon group connected to the nitrogen serves as the parent amine.
  • Other groups attached to the nitrogen are named as substituents with the prefix N- or N,N-.
• When amines contain additional functional groups, the amine group (—NH2) is treated as an amino substituent.
• Aromatic Amines: The simplest aromatic amine, featuring a benzene ring with an amino group, is known as aniline. More complex aromatic amines are named as derivatives of aniline. Substituents on the nitrogen atom in secondary and tertiary aromatic amines are located using N-.

17.4 Isomerism for Amines

• Constitutional isomerism in amines arises from: different arrangements of carbon atoms, varying positions of the nitrogen atom along the carbon chain and different partitioning of carbon atoms among carbon chains in secondary and tertiary amines.

17.5 Physical Properties of Amines

• Physical State: Methylamines and ethylamine are gases at room temperature. Most other amines exist as liquids.
• Odor: Methylamines and ethylamine (gases) possess an ammonia-like odor. Liquid amines generally have strong, disagreeable odors resembling raw fish. The foul smell of decaying flesh is due to diamines like putrescine and cadaverine, released during bacterial decomposition of protein.
• Boiling Point: Amines have boiling points intermediate between alkanes and alcohols due to weaker hydrogen bonding between H and N compared to H and O. Tertiary amines have lower boiling points than primary and secondary amines because hydrogen bonding is not possible between tertiary amine molecules.
• Solubility in Water: Amines with fewer than six carbon atoms are highly soluble in water due to hydrogen bonding between the amines and water. Even tertiary amines are water-soluble because of their ability to form hydrogen bonds.

17.6 Basicity of Amines

• Amines are basic, accepting a proton ($H^+$) from an acid, similar to ammonia ($NH_3$).
• The resulting solution is alkaline because of the presence of $OH^-$ ions and a substituted ammonium ion.
• Ammonium and substituted ammonium ions have four bonds with N and carry a + charge. Their names are derived from the parent amine, with the “-e” replaced by “ammonium ion”.

17.7 Amine Salts

• Amine salts result from the neutralization reaction between an amine (base) and an acid: Amine + Acid → Amine Salt.
• Amine salt names are written as substituted amine followed by the anion name.
• Amine slats are water soluble. Drugs of amines are administered in the form of amine salts

17.8 Preparation of Amines and Quaternary Ammonium Salts

• Primary amines in alkylation reaction mixtures can react further with alkyl halide molecules to yield secondary and tertiary amines.
• Tertiary amines react with alkyl halides in the presence of a strong base to produce quaternary ammonium salts.
• Quaternary ammonium salts differ from amine salts because the addition of a strong base does not result in the “parent” amine.
• Quaternary ammonium salts: Colorless, odorless, crystalline solids that have high melting points and are water-soluble.

17.9 Heterocyclic Amines

• Definition: Organic compounds with nitrogen atoms of amine groups present within a ring system.
  • These ring systems can be saturated, unsaturated, or aromatic.
  • Multiple nitrogen atoms may be present in a single ring and fused ring systems are common.
• Heterocyclic amines are important starting materials for medicinal, agricultural and food products, as well as being important in the human body.
  • Examples: Nicotine and Caffeine (stimulants); Porphyrin ring (component of hemoglobin).

17.10 Selected Biochemically Important Amines

• Neurotransmitters: Chemical substances released at the end of a nerve, crossing the synaptic gap to bind to receptors on another nerve, triggering a nerve impulse.
  • Acetylcholine: Involved in the transmission of nerve impulses.
  • Dopamine: Found in the brain; deficiency may cause Parkinson's disease.
  • Serotonin: Involved in sleep, sensory perception, and mental illness.
  • Norepinephrine: Helps maintain muscle tone in blood vessels.
• Epinephrine: A central nervous system stimulant released into the blood in response to pain, excitement, and fear. It increases the rate and force of heart contraction, as well as muscular strength.
• Histamine: Responsible for unpleasant effects during hay fever and pollen allergies; antihistamines are used to counter its effects.

17.11 Alkaloids

• Definition: Nitrogen-containing organic compounds extracted from plant material.
  • Well-known alkaloids include nicotine, caffeine, cocaine, morphine, and codeine.
• Many alkaloids are used in medicine:
  • Quinine (from cinchona tree bark) is used to treat malaria.
  • Atropine (from the belladonna plant) is used as a preoperative muscle relaxant.

17.12 Structure and Classification of Amides

• Amides: Derivatives of carboxylic acids in which the “-OH” group is replaced by an $NH<em>2$, NHR, or $NR</em>2$ group.
• The same rules apply to amides as to amines to determine if they are primary, secondary, or tertiary.
• Amide groups are considered as -R groups.
• Amide Classification:
  • Primary amides ($1^o$): Two hydrogen atoms bonded to the amide nitrogen.
  • Secondary amides ($2^o$): One alkyl (or aryl) group and one hydrogen atom bonded to the amide nitrogen.
  • Tertiary amides ($3^o$): Two alkyl (or aryl) groups and no hydrogen atoms bonded to the amide nitrogen.
• Lactam: A cyclic amide.
  • The ring size is indicated using a Greek letter.
  • Beta-lactam: four-membered ring.

17.13 Nomenclature for Amides

• Amides are named as derivatives of carboxylic acids.
• Rules: Change the ending of the carboxylic acid name from “-ic acid” or “-oic acid” to -amide.
  • Example: benzoic acid becomes benzamide.
• Groups attached to the nitrogen in secondary and tertiary amides are indicated with an “N-” prefix.
• The simplest aromatic amide is benzamide, with other aromatic amides named as benzamide derivatives.

17.14 Selected Amides and Their Uses

• Urea: A naturally occurring, water-soluble white solid produced in the human body from carbon dioxide and ammonia through the urea cycle: $CO<em>2 + 2NH</em>3 \rightarrow (H<em>2N)</em>2CO + H_2O$. Urea is a human nitrogen waste product, removed from the blood by the kidneys and excreted via urine. Improper kidney function can lead to urea accumulation in the blood (uremia).
• Melatonin: A polyfunctional amide; a hormone synthesized by the pineal gland that regulates the sleep-wake cycle in humans. Melatonin levels increase in the evening and decrease in the morning. Levels decrease with age. It’s used to treat insomnia and jet lag.
• Acetaminophen: A synthetic amide and a top-selling over-the-counter pain reliever, derived from acetamide.
• Barbiturates: Cyclic amides and derivatives of barbituric acid, first synthesized from urea and malonic acid. Used as tranquilizers, sedatives, and can cause death in case of overdoses.

17.15 Physical Properties of Amides

• Amides do not exhibit basic properties in solution like amines.
• Boiling Points: Monosubstituted > Disubstituted > Trisubstituted
• Monosubstituted amides are solids except for formamide, which exhibits hydrogen bonding.
• Low molecular mass amides with 5-6 carbon atoms are soluble in water.

17.16 Preparation of Amides

• Amides are produced by reacting a carboxylic acid with ammonia, a primary amine, or a secondary amine at elevated temperatures.
  • A primary amine produces a secondary amide.
  • A secondary amine produces a tertiary amide.

17.17 Hydrolysis of Amides

• Amides undergo hydrolysis to release a free acid and an amine. The reaction is catalyzed by acids, bases, or certain enzymes, and may require sustained heating.
• Under acidic conditions, the amine is converted to an amine salt. Under basic conditions, the carboxylic acid is converted to a carboxylic acid salt.

17.18 Polyamides and Polyurethanes

• Polyamides: Synthesized by combining diamines and dicarboxylic acids in a condensation polymerization reaction. Nylon is a synthetic polyamide; Nylon 66 is a polymer of 1,6-hexanediamine and hexanedioic acid monomers.
• Additional stiffness and toughness are imparted to polyamides with the introduction of aromatic rings to the polymer backbone (e.g., Kevlar).
• Silk and wool are naturally occurring polyamide polymers. The human body is also largely a polyamide polymer.
• Urethane: A hydrocarbon derivative containing a carbonyl group bonded to both an —OR group and a —NHR (or –NR2) group.
• Polyurethane: A polymer formed from the reaction of dialcohol and diisocyanate monomers. Urethane is a hydrocarbon derivative containing a carbonyl group bonded to both an —OR group and a —NHR (or –NR2) group. Polyurethane is formed from the reaction of dialcohol and diisocyanate monomers.