Heterocyclic chemistry Quinoline and Isoquiniline BSc B Ed

Heterocyclic chemistry: Quinoline and Isoquiniline BSc. B. Ed: Course Code-CHE-352 Dr. Mahender Khatravath Central University of South Bihar

v Quinoline is a heterocyclic aromatic organic compound with the chemical formula C 9 H 7 N. v Quinoline (benzo[b]pyridine) is a fused heterocyclic system consisting of a benzene ring fused with pyridine cycle. v It can be also considered as the heterocyclic analogue of naphthalene (1 -azanaphthalene). v Systematic IUPAC name: 1 -Benzopyridine; Benzo[b]azine; Benzo[b]azabenzene. v Other names: 1 -Azanaphthalene; 1 -Benzazine; Benzazabenzene; Benzopyridine; Quinolin; Chinoline; v Chinoleine; Chinolin; Leucol; Leukol; Leucoline. v Quinoline is a colourless liquid with an unpleasant odour and boiling point 2370 C. It is miscible with water, ethanol v and ether; it may be distilled by steam distillation.

Synthesis of quinoline: Skraup synthesis v The Skraup synthesis is a chemical reaction used to synthesize quinolines. It is named after the Czech chemist Zdenko Hans Skraup (1850 -1910). In the archetypal Skraup reaction, aniline is heated with sulfuric acid, glycerol, and an oxidizing agent such as nitrobenzene to yield quinoline.

Electrophilic substitution Reactions of quinolines: Quinoline and isoquinoline, the two possible structures in which a benzene ring is annelated to a pyridine ring, represent an opportunity to examine the effect of fusing one aromatic ring to another. Clearly, both the effect that the benzene ring has on the reactivity of the pyridine ring, and vice versa , as well as comparison with the chemistry of naphthalene must be considered. Firstly, it will be clear from the discussion of pyridine with electrophiles that, of the two rings, electrophilic substitution favours the benzenoid ring, rather than the pyridine ring. Regioselectivity, which in naphthalene favours an a - position, is mirrored in quinoline/isoquinoline chemistry by preferred substitution at the 5 - and 8 - positions. It should be noted that such substitutions usually involve attack on the species formed by electrophilic addition (often protonation) at the nitrogen, which has the effect of further discouraging (preventing) attack on the heterocyclic ring.

Mechanism for Nucleophilic substitution of Quinoline

Isoquinoline

The Bischler – Napieralski Synthesis

Mechanism for Bischler – Napieralski Synthesis

Pomeranz–Fritsch reaction v This synthesis is normally carried out in two stages. Firstly, an aryl aldehyde is condensed with aminoacetal to form an aryl - aldimine. This stage proceeds in high yield under mild conditions. Secondly, the aldimine is cyclised by treatment with strong acid; hydrolysis of the imine competes and reduces the effi ciency of this step and for this reason trifl uoroacetic acid with boron trifluoride is a useful reagent. v The second step is similar to those in the Combes and Skraup syntheses, in that the acid initially protonates, causing elimination of ethanol and the production of a species that can attack the aromatic ring as an electrophile. Final elimination of a second mole of alcohol completes the process.