Nitrogen Containing Organic Compounds - Amines and Other Carbon-Nitrogen Compounds

  • In this lecture, we will focus on the topic of nitrogen-containing organic compounds.

  • Amines are organic compounds that contain a nitrogen atom bonded to one or more carbon atoms.

  • Amines can be classified into three categories: primary (1°), secondary (2°), and tertiary (3°) depending on the number of carbon groups attached to the nitrogen atom.

  • Amines are commonly used as solvents, pharmaceuticals, dyes, and agricultural chemicals due to their unique properties.

  • Examples of primary amines include methylamine (CH3NH2), ethylamine (C2H5NH2), and propylamine (C3H7NH2).

Nomenclature of Amines

  • Amines are named using the suffix -amine.
  • For primary amines, the alkyl group attached to the nitrogen atom is named as a prefix.
  • For secondary amines, both alkyl groups attached to the nitrogen atom are named as prefixes.
  • For tertiary amines, all three alkyl groups attached to the nitrogen atom are named as prefixes.
  • Examples:
    • Ethylamine (C2H5NH2)
    • Dimethylamine (CH3)2NH
    • Trimethylamine (CH3)3N

Physical Properties of Amines

  • Amines have higher boiling points compared to alkanes or ethers of similar molecular weight due to intermolecular hydrogen bonding.
  • Amines with smaller alkyl groups exhibit stronger hydrogen bonding and higher boiling points.
  • The solubility of amines in water decreases as the size of the alkyl groups increases.
  • Due to the presence of a lone pair of electrons on the nitrogen atom, amines can act as weak bases and undergo protonation reactions.
  • Amines can also exhibit nucleophilic behavior, participating in reactions such as nucleophilic substitution or addition.

Preparation of Amines

  • Amines can be prepared through various methods:

    • Nucleophilic Substitution: By reacting alkyl halides with ammonia or primary/secondary amines.
    • Reductive Amination: By reducing a carbonyl compound (aldehyde or ketone) with ammonia or primary/secondary amines.
    • Gabriel Amine Synthesis: By converting phthalimide to a primary amine using hydrazine and a strong base.

  • Examples:

    • The reaction of ethyl bromide with ammonia produces ethylamine.
    • The reduction of acetophenone with methylamine yields N-methylphenylamine.
    • The Gabriel synthesis using phthalimide and hydrazine produces primary amines.

Reactions of Amines

  • Amines can undergo various reactions due to the presence of the lone pair of electrons on the nitrogen atom.
  • Amines can behave as nucleophiles, attacking electrophilic species.
  • Amines can undergo alkylation, acylation, and reductive amination reactions.
  • Aromatic amines can undergo diazonium salt reactions to form various products.
  • Examples:
    • Alkylation of amines with alkyl halides produces N-alkylated amines.
    • Acylation of amines with acyl chlorides forms amides.
    • Reductive amination can lead to the formation of secondary and tertiary amines.

Amino Acids and Peptides

  • Amino acids are organic compounds that contain both an amino group (-NH2) and a carboxyl group (-COOH).
  • Amino acids are the building blocks of proteins and play a crucial role in various biochemical processes.
  • Amino acids can be classified into essential and non-essential based on their requirement by the human body.
  • Peptides are formed by the condensation reaction between the amino group of one amino acid and the carboxyl group of another.
  • Examples:
    • Glycine, alanine, and valine are examples of amino acids.
    • The dipeptide formed by the condensation of glycine and alanine is glycylalanine.

Other Carbon-Nitrogen Compounds

  • Besides amines, there are other carbon-nitrogen compounds with unique properties and applications.
  • Nitro compounds contain a nitro group (-NO2) and are commonly used as explosives or intermediates for the synthesis of other compounds.
  • Nitriles contain a cyano group (-CN) and are used in the production of plastics, synthetic fibers, and pharmaceuticals.
  • Cyanides are highly toxic compounds; they contain a cyano group bound to any other atom than carbon.
  • Examples:
    • Nitroglycerin is a nitro compound used as an explosive.
    • Acetonitrile is a nitrile used as a solvent in organic synthesis.
    • Potassium cyanide is a cyanide compound used in gold mining.

Nomenclature of Amines

  • Amines are named using the suffix -amine.
  • For primary amines, the alkyl group attached to the nitrogen atom is named as a prefix.
  • For secondary amines, both alkyl groups attached to the nitrogen atom are named as prefixes.
  • For tertiary amines, all three alkyl groups attached to the nitrogen atom are named as prefixes.
  • Examples:
    • Ethylamine (C2H5NH2)
    • Dimethylamine (CH3)2NH
    • Trimethylamine (CH3)3N

Physical Properties of Amines

  • Amines have higher boiling points compared to alkanes or ethers of similar molecular weight due to intermolecular hydrogen bonding.
  • Amines with smaller alkyl groups exhibit stronger hydrogen bonding and higher boiling points.
  • The solubility of amines in water decreases as the size of the alkyl groups increases.
  • Due to the presence of a lone pair of electrons on the nitrogen atom, amines can act as weak bases and undergo protonation reactions.
  • Amines can also exhibit nucleophilic behavior, participating in reactions such as nucleophilic substitution or addition.

Preparation of Amines: Nucleophilic Substitution

  • Amines can be prepared through nucleophilic substitution reactions.
  • Alkyl halides (RX) react with ammonia (NH3) or primary/secondary amines to form amines.
  • This reaction involves the substitution of the halogen atom (X) with the nitrogen atom.
  • Examples:
    • Ethyl bromide (C2H5Br) reacts with ammonia (NH3) to yield ethylamine (C2H5NH2).
    • Methyl iodide (CH3I) reacts with ethylamine (C2H5NH2) to produce dimethylamine (CH3)2NH.

Preparation of Amines: Reductive Amination

  • Amines can also be prepared through reductive amination reactions.
  • Carbonyl compounds (aldehydes or ketones) react with ammonia (NH3) or primary/secondary amines to form amines.
  • The carbonyl group (C=O) is reduced to an alcohol (C-OH), and the amino group (-NH2) is introduced.
  • Examples:
    • Acetophenone reacts with methylamine to yield N-methylphenylamine.
    • Formaldehyde reacts with ethylamine to produce diethylamine.

Preparation of Amines: Gabriel Amine Synthesis

  • The Gabriel synthesis is a method to prepare primary amines.
  • Phthalimide is converted to a primary amine using hydrazine (N2H4) and a strong base like KOH.
  • The reaction involves the replacement of the phthalimide group with an amino group.
  • Examples:
    • Phthalimide reacts with hydrazine and KOH to yield primary amines.
    • N-Phenylphthalimide is converted to aniline (C6H5NH2) through the Gabriel synthesis.

Reactions of Amines

  • Amines can undergo various reactions due to the presence of the lone pair of electrons on the nitrogen atom.
  • Amines can behave as nucleophiles, attacking electrophilic species.
  • Amines can undergo alkylation, acylation, and reductive amination reactions.
  • Aromatic amines can undergo diazonium salt reactions to form various products.
  • Examples:
    • Alkylation of amines with alkyl halides produces N-alkylated amines.
    • Acylation of amines with acyl chlorides forms amides.
    • Reductive amination can lead to the formation of secondary and tertiary amines.
    • Aromatic amines can react with nitrous acid to form diazonium salts.

Amino Acids

  • Amino acids are organic compounds containing an amino group (-NH2) and a carboxyl group (-COOH).
  • Amino acids are the building blocks of proteins and play a crucial role in various biochemical processes.
  • Amino acids can be classified into essential and non-essential based on their requirement by the human body.
  • Examples of essential amino acids include lysine, leucine, and valine.
  • Amino acids exhibit both acidic and basic properties, depending on the pH of the solution.

Peptides

  • Peptides are formed by the condensation reaction between the amino group of one amino acid and the carboxyl group of another.
  • This condensation reaction results in the formation of an amide bond between the two amino acids.
  • Peptides can range from dipeptides (two amino acids) to polypeptides (many amino acids) and ultimately form proteins.
  • The primary structure of a protein is determined by the sequence of amino acids in the peptide chain.

Other Carbon-Nitrogen Compounds: Nitro Compounds

  • Nitro compounds contain a nitro group (-NO2) and are commonly used as explosives or intermediates for the synthesis of other compounds.
  • Nitro compounds are highly reactive due to the presence of the nitro group.
  • The nitro group can be reduced to an amino group through various reduction reactions.
  • Examples:
    • Nitroglycerin is a nitro compound used as an explosive.
    • Nitrobenzene is a nitro compound used in the production of dyes and pharmaceuticals.

Other Carbon-Nitrogen Compounds: Nitriles and Cyanides

  • Nitriles contain a cyano group (-CN) and are used in the production of plastics, synthetic fibers, and pharmaceuticals.
  • Nitriles can be hydrolyzed to form carboxylic acids.
  • Cyanides are highly toxic compounds that contain a cyano group bound to any other atom than carbon.
  • Cyanides are used in gold mining and as starting materials for the synthesis of various organic compounds.
  • Examples:
    • Acetonitrile is a nitrile used as a solvent in organic synthesis.
    • Potassium cyanide is a cyanide compound used in gold mining.

Importance of Nitrogen Containing Organic Compounds

  • Nitrogen-containing organic compounds play a significant role in various fields such as agriculture, pharmaceuticals, and materials science.
  • Amines are used as solvents, catalysts, and intermediates in the production of dyes, drugs, and polymers.
  • Nitro compounds are utilized as explosives, propellants, and pharmaceutical intermediates.
  • Nitriles find applications in the production of plastics, synthetic fibers, and pharmaceuticals.
  • Cyanides are important in gold mining, electroplating, and organic synthesis.

Biological Importance of Amino Acids

  • Amino acids are the building blocks of proteins, which are essential for the structure and function of cells.
  • Amino acids are involved in enzymatic reactions, regulation of gene expression, and cell signaling.
  • They provide energy and participate in metabolic processes such as the synthesis of hormones and neurotransmitters.
  • Amino acids are essential for human nutrition as they cannot be synthesized by the body and must be obtained through diet.
  • Imbalances or deficiencies in amino acids can lead to various health issues.

Pharmaceutical Applications of Amines

  • Amines find extensive use in the pharmaceutical industry.
  • They are employed as active ingredients in drugs for the treatment of various diseases such as hypertension, depression, and allergies.
  • Amines can act as receptor agonists or antagonists, affecting cell signaling pathways.
  • Many anticancer drugs contain amine groups that target specific receptors in cancer cells.
  • Amines are also used in the synthesis of drug delivery systems and the modification of drug properties.

Synthesis of Amines through Gabriel Amine Synthesis

  • Gabriel amine synthesis is a method to prepare primary amines.
  • It involves the reaction of phthalimide with hydrazine (N2H4) and a strong base, such as potassium hydroxide (KOH).
  • The reaction proceeds through the formation of an intermediate, followed by the replacement of the phthalimide group by the amino group.
  • The resulting primary amine can be isolated and used for various applications.
  • Example: Phthalimide reacts with hydrazine and KOH to yield primary amines.

Reaction of Amines with Nitrous Acid

  • Aromatic amines can react with nitrous acid (HNO2) to form diazonium salts.
  • Diazonium salts are versatile intermediates used in the synthesis of various compounds, including dyes, pigments, and pharmaceuticals.
  • Diazonium salts can undergo coupling reactions to produce azo compounds, which exhibit intense colors.
  • Example: Aniline (C6H5NH2) reacts with nitrous acid to form the diazonium salt.

Application of Nitroglycerin as an Explosive

  • Nitroglycerin (C3H5N3O9) is a powerful explosive used in mining, construction, and military applications.
  • It releases a large amount of energy upon detonation due to the decomposition of nitroglycerin into gases.
  • The controlled use of nitroglycerin in dynamite and other explosives makes it an essential compound in the industry.
  • Nitroglycerin is highly sensitive and requires careful handling and storage due to its instability.
  • Example: The decomposition reaction of nitroglycerin can be represented as 4C3H5N3O9 → 6N2 + 12CO2 + 10H2O + O2 + energy.

Synthesis of Nitriles through Nitrile Hydrolysis

  • Nitriles can be hydrolyzed to form carboxylic acids in the presence of an acid or a base.
  • The reaction involves the cleavage of the carbon-nitrogen triple bond, resulting in the formation of a carboxyl group (-COOH).
  • Nitrile hydrolysis is an important step in the synthesis of pharmaceuticals, organic acids, and polymers.
  • The choice of acid or base used in the hydrolysis determines the yield and selectivity of the reaction.
  • Example: Acetonitrile can be hydrolyzed to form acetic acid (CH3COOH) in the presence of an acid or a base.

Biological Toxicity of Cyanide Compounds

  • Cyanide compounds are highly toxic to living organisms, including humans.
  • They interfere with cellular respiration by inhibiting the enzymes involved in the electron transport chain.
  • Cyanide poisoning can lead to symptoms such as dizziness, headache, nausea, and, in severe cases, respiratory failure and death.
  • However, cyanide compounds can also be used for therapeutic purposes, such as in cancer treatments.
  • Cyanide poisoning requires immediate medical attention and specific antidotes like hydroxocobalamin or sodium thiosulfate.

Uses of Nitriles in Pharmaceutical Industry

  • Nitriles find significant use in the pharmaceutical industry.
  • They serve as intermediates in the synthesis of various drugs, particularly those targeting the central nervous system and cardiovascular system.
  • Nitriles can be transformed into amides or amines, which are crucial components of many medications.
  • Nitriles are utilized in the development of inhibitors for enzymes involved in diseases like hypertension and diabetes.
  • Example: Acetonitrile can be converted into valsartan, a widely used antihypertensive drug.

Environmental Concerns with Nitro Compounds and Cyanides

  • Nitro compounds and cyanides pose environmental concerns due to their toxicity and persistence in the environment.
  • Uncontrolled release of nitro compounds can contribute to soil and water pollution, impacting ecosystems and human health.
  • Cyanide compounds can contaminate water bodies through industrial waste or mining activities, causing severe harm to aquatic life.
  • Proper waste management, treatment methods, and regulation are essential to minimize the environmental impact of these compounds.
  • Researchers are actively working towards developing greener and safer alternatives to mitigate the environmental risks associated with these compounds.