6- -quinoline, reaction

A well understood case is that of quinoline reaction at position 2 is kinetically favored as compared with reaction at position 4, but the adduct from the latter is thermodynamically more stable. This situation, where the site of attack leading to the more stable adduct is the y position, is analogous with those regarding the formation of Meisenheimer adducts from benzene and pyridine derivatives and RCT nucleophiles. Presumably, with quinoline kinetic control favors the position that is more strongly influenced by the inductive effect of the heteroatom. The fact that position 2 of quinoline is the most reactive toward nucleophilic reagents is probably related to the lower 71-electron density at that position.123 However, the predominance of the C-4 adduct at equilibrium can be better justified by the atom localization energies for nucleophilic attachment at the different positions of quinoline. Moreover, both 7t-electron densities and atom localization energies indicate position 1 of isoquinoline to be the most favored one for nucleophilic addition. 

For quinoline, reaction on the neutral species would require that 5- and 8-substitution would be sterically hindered, since o+ values (Section 7) predict the order 5 > 8 = 6 > 3. However, it seems improbable that steric hindrance is that severe and, moreover, the order for the unhindered 3-and 6-positions is the wrong way around. An alternative explanation is that bromination occurs on an intermediate addition product. This takes account of the fact that the 3-, 6-, and 8-positions may all conjugate with a lone pair on nitrogen. The order 3 > 6 > 8 would then precisely follow from such conjugation, since resonance to the 6- and 8-positions requires interruption of the benzenoid conjugation, and resonance is always re-... 

Alkaline treatment of 36 gave the 5,10-dihydro compound 37. This was also obtained directly by refluxing the diamine 38 and the chlorodinitropyridine 39 in quinoline.Reaction of 37 with iron and ferric chloride gave the charged species 40. 

See the very similar Knorr Quinoline Reaction, conducted with the same reagents at elevated temperatures. 

Formation of indole derivative by the reaction of 2-ethynylaniline, aryl halide and CO is known [53]. Cacchi extended the reaction to the synthesis of indolo[3.2-c]quinoline. Reaction of 2-(2 -aminophenylethynyl)trifluoroacetanilide 122, 4-iodoanisole and CO occurred as shown by 123 to provide 124 and then the 3-aroylindole 125. Treatment of 125 with a base gave the indoloquinoline 126 in 70% overall yield [54]. 

Isoquinoline (79) reacts similarly to quinoline. Reaction of isoquinoline with nitric acid/sulfuric acid gives a mixture of 5-nitroisoquinoline (101) and 8-nitroisoquinoline (102), but 101 is produced in about 90% yield. 

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