Hetrocyclic Compounds.pptx

Hetrocyclic Compounds Definition: “Heterocyclic compounds are cyclic hydrocarbons contain one or more heteroatoms in a ring.” OR “Any of a class of organic compounds whose molecules contain one or more rings of atoms with at least one atom (the heteroatom)...

Hetrocyclic Compounds Definition: “Heterocyclic compounds are cyclic hydrocarbons contain one or more heteroatoms in a ring.” OR “Any of a class of organic compounds whose molecules contain one or more rings of atoms with at least one atom (the heteroatom) being an element other than carbon, most frequently oxygen, nitrogen, or sulfur.” They may be aromatic, or partially or fully saturated.  Examples: Aromatic Six-Membered Compounds.  Examples: Aromatic Five-Membered Compounds.  Examples: Saturated Heterocyclic Compounds. Examples: Unsaturated Heterocyclic Compounds.  Conti… Heterocyclic compounds include many of the biochemical material essential to life. For example, nucleic acids, the chemical substances that carry the genetic information controlling inheritance, consist of long chains of heterocyclic units held together. Many pharmaceuticals and agrochemicals contain at least one heterocyclic unit. Many naturally occurring pigments, vitamins, and antibiotics are heterocyclic compounds.  Quinoline Definition: “Quinoline, also known as benzo-pyridine is a heterocyclic aromatic organic compound with the chemical formula C₉H₇N.” Structure: Quinoline is characterized by a double ring structure composed of a benzene and a pyridine ring fused at two adjacent carbon atoms.  It is a colorless hygroscopic liquid with a strong odor. Physical Properties: Boiling point 238ºC. Melting point -15°C. Density at 25°C is 1.09 g/cm³. Absorbs as much as 22% water and is volatile with steam. It is slightly soluble in cold water but dissolves readily in hot water and most organic solvents. Miscible with alcohol, ether and carbon disulphide. Dissolves sulphur, phosphorus and arsenic trioxide. Quinoline is also known as benzo(b)pyridine or 1-aza-naphthalene. It is a weak tertiary base.  Resonance structures of Quinoline Quinoline shows aromatic properties because the resulting molecular orbital satisfies the Huckle’s rule (4n+2 rule). The nitrogen lone pair is not released into the aromatic system because it is perpendicular to the p system. The nitrogen withdraws electrons by resonance, resulting in an electron-deficient ring system. The resonance phenomena increase the stability of the quinoline ring. Quinoline is the mixture of the following six resonance structures: Methods of Prepartion: Skraup synthesis: The Skraup synthesis is a chemical reaction used to synthesize quinolines. Aniline is heated with sulphuric acid, glycerol, and an oxidizing agent, like nitrobenzene to yield quinoline.  Combes Quinoline Synthesis: It involves the condensation of unsubstituted anilines (1) with β-diketones (2) to form substituted quinolines after an acid catalyzed ring closure of an intermediate Schiff base. Note: A Schiff base is a compound with the general structure R2C=NR' (R' ≠ H). They can be considered a sub-class of imines, being either secondary ketimines or secondary aldimines depending on their structure.  Friedländer Synthesis of Multisubstituted Quinolines: General Reaction: An Example: It involves condensation of o-amino benzaldehyde with acetaldehyde in the presence of an alkali.  Niementowski quinoline synthesis: The Niementowski quinoline synthesis is the chemical reaction of anthranilic acids and ketones (or aldehydes) to form γ- hydroxyquinoline derivatives. Dobener Reaction: The Dobener reaction is the chemical reaction of an aniline with an aldehyde and pyruvic acid to form quinoline-4-carboxylic acids. Chemical Reactions: Basic Character: Quinoline is slightly weaker base than pyridine. It reacts with acids to yield salts which are sparingly soluble in water. Electrophilic substitution reaction: Benzene ring is more electron rich than pyridine ring. Undergo electrophilic substitution in benzene ring and not in the more resistent pyridine ring. The elctrophile attacks position 8 and 5.  Nitration: Sulphonation:  Halogenation: Nucleophilic substitution reaction: Quinoline readily gives nucleophilic substitution reaction shown by pyridine ring. It reacts with Sodium Amide (NaNH2) to give 2- Aminoquinoline. If any substitution present at C-2 position then reaction occur at C-4 position.  Reaction with KOH: Reaction with n-butyl lithium: Reaction with per acetic acid:  Oxidation Reaction with KMnO4: Quinoline undergo oxidative cleavage with alkaline potassium permangnate to give pyridine-2,3-dicarboxylic acid. However, pyridine-2,3- dicarboxylic acid is not stable and undergoes decarboxylation to give nicotinic acid.  Reduction: Reaction with alkyl halides:  Quinoline ring has been found to possess antimalarial, anti-bacterial, antifungal, Pharmaceutical and Medical Applications anthelmintic (a group of antiparasitic drugs that expel internal parasites from the body), cardiotonic (drugs that increase the contracting mechanism within the heart), anticonvulsant (drugs used in the treatment of epileptic seizures), anti- inflammatory, and analgesic activity. Quinoline family compounds are widely used as a parent compound to make drugs (especially anti-malarial medicines such as Chloroquine and hydroxychloroquine), fungicides and biocides. Chloroquine is a completely synthetic anti-malarial drug that has the quinoline system found in quinine. They have antiseptic, antipyretic (substances that reduce fever), and antiperiodic (Preventing regular recurrence of the symptoms of a disease, as in malaria) properties.  Quinaldine, 2-methylquinoline, is used as an anti-malarial and preparing other anti- malarial drugs. Quinazoline, diazanaphthalene at 1,3 positions, is used as a chemical intermediate for making medicines and other organic compounds. It is a fundamental structure in some antihypertensive agents such as prazosin and doxazosin which are peripheral vasodilator. Quinoxaline, diazanaphthalene at 1,4 positions, is used as a chemical intermediate for making fungicides and other organic compounds.  Quinine is an anti-malarial natural product isolated from the bark of the Cinchona tree.