4-Fluorinated isoquinoline, formation

Ring-fluorinated isoquinoline derivatives thus synthesized exhibit a wide range of bioactivities that rival or surpass those of the original fluorine-free compounds, hi addition to such remarkable potentials in the field of pharmaceutical sciences, the formation of supramolecular structures and the use of ligands of light-emitting metal complexes have also attracted considerable attention as possible functions of fluoroisoquinolines. This section describes conaete examples of the properties and applications of fluoroisoquinoline derivatives. 

Bicyclomycin rearrangement product, synthesis, 57, 224 2,2 -Bifuran, 5,5 -dibromo-, 57, 306 2,2 -Biimidazoles bromination, 57, 350 chlorination, 57, 347 2,2 -Biindolyl, synthesis, 56, 174 l,l -Biisoquinoline. formation from isoquinoline and LDA, 56, 245 fiimanes, fluorination by acetyl hypofluorite, 59, 4 Biological properties of heterocyclic betaines and precursors, 60, 250-1... 

Oxazoles.—Formation. ci)-Diazoacetophenone reacts with benzonitrile in the presence of trifluoromethanesulphonic acid to give 2,5-diphenyloxazole (514). Bi-, ter-, and quater-oxazoles have been synthesized from a-metallated isocyanides thus lithiobenzyl isocyanide (PhCHLiNC) and dimethyl oxazole-3,4-dicarboxylate afford compound (515). Stable methylene-oxazolines (516 R = Me or Ph) are obtained by heating the iminesHN=C(Ph)OCHRC=CH. The fluorinated oxazoline (518) results from the action of benzonitrile on the oxiran (517), and also from the reaction of bis(trifluoromethyl)carbene with the benzoylimine (CF3)2C=NCOPh/ Treatment of 2-acylamino-l-aryl-alkan-l-ols (519) under the conditions of the Pictet-Gams reaction, i.e. with phosphorus pentoxide in boiling toluene or xylene, results in cis- and trans-2-oxazolines (520), rather than isoquinolines, as claimed previously. The spiro-oxazolines (521 R = Me or Ph) are formed when the lithiated di-isocyanide CN—CH2CH2CHLi—NC is treated with acetone or benzophenone, respec-tively. ... 

When pentafluoropyridine and heptafluoro-quinoline and -isoquinoline react with hydrogen diloride or bromide in suipholane, replacement of fluorine ortho and para to the nitrogen by halogen occurs. The order of reactivity is heptafluoroquinoline > heptafluoroisoquinoline > pentafluoropyridine traces of water lead to a considerable rediKtion in the reaction rate and to the formation of hydroxy-daivatives. The proposed mechanism for these reactions, involving nucleophilic displacement of fluoride ion from the protonated heterocycle, is illustrated for heptafluoroquinoline in Scheme 52. No evidence for initial attack at the 4-position was obtained, mid 2,4-dichloro-pentafluoroquinoline was obtained in high yield. 

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