Isoquinolines, halo-, amination

The rate of amination and of alkoxylation increases 1.5-3-fold for a 10° rise in the temperature of reaction for naphthalenes (Table X, lines 1, 2, 7 and 8), quinolines, isoquinolines, l-halo-2-nitro-naphthalenes, and diazanaphthalenes. The relation of reactivity can vary or be reversed, depending on the temperature at which rates are mathematically or experimentally compared (cf. naphthalene discussion above and Section III,A, 1). For example, the rate ratio of piperidination of 4-chloroquinazoline to that of 1-chloroisoquino-line varies 100-fold over a relatively small temperature range 10 at 20°, and 10 at 100°. The ratio of rates of ethoxylation of 2-chloro-pyridine and 3-chloroisoquinoline is 9 at 140° and 180 at 20°. Comparison of 2-chloro-with 4-chloro-quinoline gives a ratio of 2.1 at 90° and 0.97 at 20° the ratio for 4-chloro-quinoline and -cinnoline is 3200 at 60° and 7300 at 20° and piperidination of 2-chloroquinoline vs. 1-chloroisoquinoline has a rate ratio of 1.0 at 110° and 1.7 at 20°. The change in the rate ratio with temperature will depend on the difference in the heats of activation of the two reactions (Section III,A,1). 

Azine approach. Oxazolo[3,2-a]pyridinium salts (210) were first obtained from the cyclodehydration reaction of l-phenacyl-2(lii)-pyridinone in sulfuric acid (67JHC66). These salts can also be prepared from 2-halo-l-phenacylpyridinium derivatives (211) by treatment with a base which causes ylide formation and hence cyclization by intramolecular substitution (69JOC2129, 76CB3646). It is recommended that a bulky tertiary amine is used as base in order to avoid opening of the ring or substitution of the 2-halo substituent in the starting material (211). Isoquinoline and quinoline analogues have also been prepared by these methods. 

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