Nitrogen Containing Organic Compounds - Some Biologically Important Amines

  • Organic compounds that contain nitrogen atom(s) are called nitrogen-containing organic compounds or amines.
  • Amines are derived from ammonia (NH3) by replacing one or more hydrogen atoms with organic groups (R).
  • Amines are classified as primary (1°), secondary (2°), or tertiary (3°) based on the number of alkyl or aryl groups attached to the nitrogen atom.
  • Amines have a characteristic ammonia-like odor due to their ability to form hydrogen bonds with water molecules.
  • Amines can be synthesized via various methods such as reduction of nitro compounds, nucleophilic substitution reactions, and reductive amination.

Naming Amines

  • Primary amines are named by prefixing the name of the alkyl or aryl group with “amino-”.
  • Secondary amines are named by using N-alkyl prefix for the alkyl group attached to the nitrogen.
  • Tertiary amines are named by using N,N-dialkyl prefix for the two alkyl groups attached to the nitrogen.

Physical Properties

  • Amines exhibit intermolecular hydrogen bonding due to the presence of a nitrogen lone pair.
  • Lower molecular weight amines are soluble in water, while higher molecular weight amines are less soluble.
  • Amines have lower boiling points compared to alcohols and carboxylic acids of similar molecular weights.
  • Amines have a higher boiling point than hydrocarbons due to intermolecular hydrogen bonding.

Basicity of Amines

  • Amines are weak bases due to the presence of a lone pair of electrons on the nitrogen atom.
  • They react with acids to form salts.
  • The basicity of amines is affected by the degree of substitution on the nitrogen atom.
  • Primary amines are more basic than secondary amines, which are more basic than tertiary amines.

Reactions of Amines

  • Amines can undergo various organic reactions such as nucleophilic substitution, oxidation, and condensation.
  • Nucleophilic substitution reactions of amines involve the substitution of the nitrogen atom with a different group.
  • Amines can be oxidized to form nitro compounds or to undergo oxidative deamination.
  • Condensation reactions of amines can lead to the formation of imines, enamines, or Schiff bases.

Biological Importance of Amines

  • Amines play significant roles in biological processes.
  • They are involved in the synthesis of neurotransmitters, hormones, and vitamins.
  • Important examples of biologically important amines include dopamine, serotonin, adrenaline, and histamine.
  • Amino acids, the building blocks of proteins, contain an amine group.
  • Amines can also act as drugs or toxins in the body.

Examples of Biologically Important Amines

  1. Dopamine
  1. Serotonin
  1. Adrenaline
  1. Histamine
  1. Epinephrine
  1. Noradrenaline
  1. Acetylcholine
  1. GABA (gamma-aminobutyric acid)
  1. Tryptamine
  1. Norepinephrine

Dopamine - Example of a Biologically Important Amine

  • Dopamine is a neurotransmitter involved in various physiological functions.
  • It plays a role in mood regulation, movement control, and reward reinforcement.
  • Dopamine imbalance in the brain is associated with several neurological disorders such as Parkinson’s disease and schizophrenia.
  • Dopamine is synthesized from the amino acid tyrosine via enzymatic reactions.

Serotonin - Example of a Biologically Important Amine

  • Serotonin is a neurotransmitter and hormone that is involved in the regulation of mood, sleep, and appetite.
  • It is synthesized from the amino acid tryptophan.
  • Imbalances in serotonin levels are associated with mood disorders such as depression and anxiety.
  • Serotonin is also involved in the regulation of gastrointestinal functions.

Synthesis of Amines

  • Reduction of Nitro Compounds:

    • Nitro compounds (R-NO2) can be reduced to primary amines (R-NH2) using reducing agents such as hydrogen gas in the presence of a catalyst (e.g., Raney nickel) or using metal hydrides like LiAlH4.
    • Example: Nitrobenzene can be reduced to aniline.

  • Nucleophilic Substitution:

    • Amines can be synthesized by nucleophilic substitution reactions of halides or alkyl/acyl halides with ammonia or amines.
    • Example: Ethyl bromide can undergo nucleophilic substitution with ammonia to form ethylamine.

  • Reductive Amination:

    • Aldehydes or ketones react with primary or secondary amines in the presence of reducing agents (e.g., sodium borohydride) to form amines.
    • Example: Acetaldehyde reacts with methylamine to form N-methyl-ethanamine (methylamine).

  • Gabriel Amine Synthesis:

    • Phthalimide reacts with an alkyl halide in the presence of a strong base (e.g., potassium hydroxide) to form a primary amine.
    • Example: Reaction of phthalimide with 1-bromobutane yields n-butylamine.

Nitro Compounds

  • Nitro compounds have a nitro group (-NO2) attached to a carbon atom.
  • They can act as intermediates in the synthesis of amines.
  • Nitro compounds are often used as explosives due to their high stability.
  • Reduction of nitro compounds results in the formation of amines.
  • Example: Nitroethane can be reduced to ethylamine.

Nucleophilic Substitution Reactions

  • Nucleophilic substitution reactions involve the substitution of an atom or group with a nucleophile (electron-rich species).
  • In the context of amine synthesis, the nitrogen of the amine or ammonia acts as a nucleophile.
  • Nucleophilic substitution reactions can occur with alkyl halides, acyl halides, or alkyl sulfonates as the electrophilic substrate.
  • Example: The nucleophilic substitution of methyl bromide with ammonia yields methylamine.

Reductive Amination

  • Reductive amination is a method used to synthesize primary and secondary amines.
  • It involves the reaction of an aldehyde or ketone with ammonia or a primary/secondary amine in the presence of a reducing agent.
  • The reducing agent helps convert the imine intermediate to the corresponding amine.
  • Example: The reductive amination of benzaldehyde with methylamine yields N-methylbenzylamine.

Gabriel Amine Synthesis

  • Gabriel amine synthesis is a method used to prepare primary amines.
  • It involves the reaction of phthalimide with an alkyl halide in the presence of a strong base.
  • The alkyl group from the alkyl halide replaces the phthalimide group to form the primary amine.
  • Example: The Gabriel synthesis of n-butylamine involves the reaction of phthalimide with 1-bromobutane.

Oxidation of Amines

  • Amines can be oxidized to form nitro compounds or undergo oxidative deamination.
  • Oxidation of amines typically requires strong oxidizing agents such as potassium permanganate (KMnO4) or chromic acid (H2CrO4).
  • Example: Primary amine oxidation can yield nitro compounds, while secondary amines are oxidized to form imines.

Condensation Reactions of Amines

  • Condensation reactions of amines involve the formation of a new bond by combining amines with carbonyl compounds (aldehydes or ketones).
  • The reaction forms an imine (primary amine) or an enamine (secondary amine).
  • Example: Reaction of an aldehyde (e.g., formaldehyde) with an amine (e.g., aniline) can form an imine.

Schiff Base Formation

  • Schiff base formation is a specific type of condensation reaction between a primary amine and an aldehyde or ketone.
  • The reaction results in the formation of a Schiff base, which contains a carbon-nitrogen double bond (-C=N-).
  • Schiff bases are important intermediates in various organic reactions and can be used as ligands in coordination chemistry.
  • Example: The reaction of benzaldehyde with aniline can form a Schiff base.

Biological Role of Amines - Neurotransmitters

  • Amines play a crucial role in biological systems as neurotransmitters.
  • Neurotransmitters are chemical messengers responsible for transmitting signals within the nervous system.
  • Examples of amine neurotransmitters: dopamine, serotonin, adrenaline, acetylcholine.
  • These neurotransmitters regulate various physiological processes such as mood, cognition, and motor control.

Biological Role of Amines - Hormones

  • Amines also function as hormones in the body, acting as chemical messengers that regulate various physiological processes.
  • Examples of amine hormones: epinephrine, norepinephrine.
  • Epinephrine (adrenaline) is involved in the body’s fight-or-flight response, regulating heart rate, blood pressure, and metabolism.
  • Norepinephrine is involved in stress response, arousal, and attention regulation.

Slide 21:

  • Biological Role of Amines - Neurotransmitters (continued)
  • Dopamine: Regulates pleasure, motivation, and movement. Imbalances linked to Parkinson’s disease and schizophrenia.
  • Serotonin: Regulates mood, sleep, and appetite. Imbalances linked to depression and anxiety disorders.
  • Adrenaline: Involved in fight-or-flight response, increasing heart rate and blood flow.
  • Acetylcholine: Plays a role in muscle movement, memory, and learning.

Slide 22:

  • Biological Role of Amines - Hormones (continued)
  • Epinephrine (Adrenaline): Released during stress, increases heart rate, and prepares the body for action.
  • Norepinephrine: Regulates stress response, attention, and arousal.

Slide 23:

  • Amino Acids: Building Blocks of Proteins
  • Amino acids are organic compounds containing both an amino group (-NH2) and a carboxyl group (-COOH).
  • They are the building blocks of proteins, which play essential roles in cell structure and function.
  • Amino acids differ in their side chains (R groups), which determine their properties and functions.
  • Example: Glycine, the simplest amino acid, has a hydrogen atom as its side chain.

Slide 24:

  • Peptide Bond Formation
  • Amino acids are linked together through peptide bonds to form polypeptides or proteins.
  • Peptide bond formation involves the condensation reaction between the carboxyl group of one amino acid and the amino group of another.
  • Water is eliminated in the process, and a peptide bond is formed.
  • Example: Glycine and alanine can form a dipeptide by peptide bond formation.

Slide 25:

  • Classification of Amino Acids
  • Amino acids can be classified based on various properties, including their side chains (R groups) and charge.
  • Nonpolar Amino Acids: Side chains contain mostly hydrocarbon groups. Examples: Alanine, Valine, Leucine.
  • Polar Amino Acids: Side chains contain functional groups like hydroxyl (-OH) or amide (-CONH2). Examples: Serine, Asparagine.
  • Acidic Amino Acids: Side chains contain carboxyl groups (COOH). Examples: Aspartic acid, Glutamic acid.
  • Basic Amino Acids: Side chains contain amino groups (NH2). Examples: Lysine, Arginine.

Slide 26:

  • Acid-Base Behavior of Amino Acids
  • Amino acids can act as both acids (proton donors) and bases (proton acceptors) due to their carboxyl and amino groups.
  • In neutral solutions, amino acids exist as zwitterions, with a positive and negative charge on different parts of the molecule.
  • The pKa values of the carboxyl and amino groups determine the acid-base behavior of amino acids.
  • Example: The amino acid glycine exists as a zwitterion in neutral solutions.

Slide 27:

  • Isoelectric Point (pI) of Amino Acids
  • The isoelectric point (pI) is the pH at which an amino acid has no net charge.
  • At pH values above the pI, the amino acid carries a net negative charge.
  • At pH values below the pI, the amino acid carries a net positive charge.
  • Example: The pI of glycine is around pH 5.97.

Slide 28:

  • Peptides and Proteins
  • Peptides are short chains of amino acids linked by peptide bonds.
  • Proteins are larger, complex molecules made up of one or more polypeptide chains.
  • The structure and function of proteins depend on the sequence and arrangement of amino acids.
  • Example: Insulin, a hormone, is composed of two polypeptide chains linked by disulfide bonds.

Slide 29:

  • Denaturation of Proteins
  • Denaturation refers to the disruption of a protein’s structure and loss of its function.
  • Factors such as heat, pH extremes, and certain chemicals can denature proteins.
  • Denaturation can lead to loss of enzyme activity, altered protein structure, and loss of biological function.
  • Example: Cooking an egg denatures the protein in egg whites, changing its texture and appearance.

Slide 30:

  • Summary
  • Amines are nitrogen-containing organic compounds derived from ammonia.
  • They play important roles in biology as neurotransmitters, hormones, and amino acids.
  • Amines can be synthesized through various methods like reduction, nucleophilic substitution, and reductive amination.
  • Amino acids are the building blocks of proteins and can act as both acids and bases.
  • Peptide bond formation links amino acids to form peptides and proteins.
  • Denaturation disrupts protein structure and function.