qunolin and isoqunoline.pptx

Fused ring heterocycles Quinoline and isoquinoline (benzopyridines) man Mahmood Hassan ty of pharmacy/ pharmaceutical chemistry 20  Fused ring heterocycles (A) Quinoline and isoquinoline (benzopyridines) Two isomeric benzo pyridines are...

Fused ring heterocycles Quinoline and isoquinoline (benzopyridines) man Mahmood Hassan ty of pharmacy/ pharmaceutical chemistry 20  Fused ring heterocycles (A) Quinoline and isoquinoline (benzopyridines) Two isomeric benzo pyridines are quinoline and isoquinoline. Quinoline is the benzo[b]pyridine and isoquinoline is the benzo[c]pyridine isomer. These two are very important heterocyclic units because their derivatives widely occur in nature as alkaloids. For example, the antimalarial quinine and the pain reliever morphine. Dr. Eman Mahmood Hassan Faculty of  General properties  Both of these compounds are basic in nature  The lone pair of electrons on the nitrogen atom is not utilized in the internal resonance for the aromaticity of the compounds.  Unlike benzene, the bond lengths of both the compounds are irregular, and both of them possess considerable dipole moment directed toward the nitrogen atom.  Both of these compounds react with acids and Lewis acids at the basic nitrogen atom, forming quinolium and isoquinolium salts, respectively. Dr. Eman Mahmood Hassan Faculty of  Therefore, the products of electrophilic substitution of the compounds depend on the nature of the reagent used for the reaction. Since the electron density of the pyridine ring is lower than that of the benzene ring, the electrophilic substitutions of both quinoline and isoquinoline take place in the benzene ring. 1. The For nitration of quinoline with fuming nitric acid in example, concentrated (conc.) sulfuric acid containing SO3 at room temperature gives a mixture of 5-nitro-and 8-nitroquinolines, whereas isoquinoline reacts with same reagent at 0°C to give a mixture of 5- and 8- nitro isoquinolines. Dr. Eman Mahmood Hassan Faculty of  2. Sulfonation of quinoline with oleum at 92°C gives mainly quinoline-8-sulfonic acid. But, isoquinoline under similar condition gives isoquinoline-5-sulfonic acid. Dr. Eman Mahmood Hassan Faculty of  3. Alkyl and acyl halides react directly with the basic nitrogen atom of both the compounds to give quaternary salts. However, with acetyl nitrate at 20°C, quinoline undergoes an addition- substitution reaction to give 3-nitroquinoline. Isoquinoline undergoes no such reaction in the pyridine ring. Dr. Eman Mahmood Hassan Faculty of  The C=N bond of the pyridine ring in both of these compounds under goes nucleophilic addition at low temperature with KNH2, and the adduct on oxidation with KMnO4 at low temperature gives 2-aminoquinoline and 1-aminoisoquinoline in a Chichibabin-type reaction. Dr. Eman Mahmood Hassan Faculty of  Synthesis of benzopyridines (quinoline & isoquinoline ) 1. Synthesis of quinoline: Skraup synthesis A mixture of glycerol, aniline, sulfuric acid, nitrobenzene, and ferrous sulfate and heating gives quinoline. Glycerol is dehydrated by sulfuric acid to acrolein. Aniline undergoes a Michael-type addition with acrolein in an acid-promoted reaction to form β-anilinopropanal that, in turn, undergoes an acid-catalysed cyclization to give 1,2- dihydroquinoline. Nitrobenzene aromatizes this dihydro compound to quinoline Dr. and itself Eman Mahmood Hassan Faculty of This method can be applied to synthesize benzene ring-substituted quinoline provided the substituents are not strongly deactivating in nature. Dr. Eman Mahmood Hassan Faculty of  2. Synthesis of isoquinoline (a) Bischler–Napieralski synthesis. 1-Alkyl isoquinolines can be synthesized by this method, which involves the following steps: Dr. Eman Mahmood Hassan Faculty of  (b) Pomeranz–Fritsch reaction. The parent compound, that is, isoquinoline can be synthesized by this reaction, which is as follows Dr. Eman Mahmood Hassan Faculty of Dr. Eman Mahmood Hassan Faculty of  a n s san r. Em od Ha o D o t h m Ma n k s Th a n st e Li