Oxyquinolines and-isoquinolines

Quinolinols and isoquinolinols in which the oxygen is at any position other than 2-and 4- for quinolines and 1- and 3- for isoquinolines are true phenols i.e. have an hydroxyl group, though they exist in equilibrium with variable concentrations of zwitterionic structures with the nitrogen protonated and the oxygen deprotonated. They show the typical reactivity of naphthols. 8-Quinolinol has long been used in 

2-Quinolone (strictly 2(l/f)-quinoIinone) and 4-quinolone and 1-isoquinolone are completely in the carbonyl tautomeric form for all practical purposes - the hydroxyl tautomers lack a favourable polarised resonance contribution, as illustrated below for 1-isoquinolone. There is considerable interest in quinolones as antibacterial agents.  

In 3-oxy-isoquinoline there is an interesting and instructive situation here the two tautomers are of comparable stability. 3-Isoquinolinol is dominant in dry ether solution, 3-isoquinolone is dominant in aqueous solution. A colourless ether solution of 3-isoquinolinol turns yellow on addition of a little methanol because of the production of some of the carbonyl tautomer. The similar stabilities is the consequence of the balancing of two opposing tendencies the presence of an amide unit in 3-isoquinolone forces the benzene ring into a less favoured quinoid structure, conversely, the complete benzene ring in isoquinolinol necessarily means loss of the amide unit and its contribution to stability. One may contrast this with 1-isoquinolone which has an amide, as well as a complete benzene, unit.  

The position of electrophilic substitution of quinolones and isoquinolones depends upon the pH of the reaction medium. Each type protonates on carbonyl oxygen so reactions in strongly acidic media involve attack on this cation the contrast can be illustrated by the nitration of 4-quinolone at different acid strengths. The balance between benzene ring and unprotonated heterocyclic ring selectivity is small, for example 2-quinolone chlorinates preferentially, as a neutral molecule, at C-6, and only secondly at C-3. 

Strong acid-catalysed H-exchange of 2-quinolone proceeds fastest at C-6 and C-8 of 1-isoquinolone at C-4, then 5-1. This is echoed in various electrophilic substitutions, for example formylation.  

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