Quinolines alkoxylation

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). 

Heteroaromatic fluorination. Fluorination of pyridine, quinoline, and quinoxaline systems occurs with fluorine-iodine mixtures. Pyridine is alkoxylated when an appropriate alcohol is present. 

Indolinonic and quinolinic aromatic nitroxides have been shown to efficiently scavenge all kinds of radicals. They couple with carbon-centred radicals, giving alkylated hydroxylamines (Carloni 1991, Stipa et al. 1997), and unlike the aliphatic nitroxides, they react with all oxygen-centred radicals such as hydroxyl (Damiani et al. 1999), alkoxyl (Greci 1982), peroxyl (Cardellini et al. 1989), and aroyloxyl (Berti et al. 1977) to form nonpara-magnetic compounds. From a study by Daminani et al. 2000) it seems that a structure activity relationship determined by the type of ring system and its substituents (to which the nitroxide function is attached) could exist. 

This way of rationalization is substantiated by the photolytic behavior of, -unsaturated aldehydes (478) (Scheme 162). Only in one of the five cases studied was 479 observed this result is in accordance with the difficult intramolecular addition of alkoxyl radicals in the Cy6/Cy7 case. Since thiyl cyclizations appear efficient even in the Cy6/Cy7 case one might expect to observe easy photocyclizations of unsaturated thiones also in this case the easy photochemical synthesis of quinolines from A -(o-styryl)thioamides appears to be an excellent illustration of this view. Here, the sulfur analog of 479 would be an intermediate. To complete the analogy, one may expect the converse P-scission reaction to be efficient with radicals that readily open such as oxyranylalkyl ones (see Section VIII.2) in this way an interesting macrolide synthesis was described by Carlson. Photolysis of epoxycyclanone (480)... 

Quinoline directs alkoxylation and phenoxylation of tethered arenes. The 8-aminoquinoline directs the copper oxidation of the sp C-H bond (Scheme 76) (130L5842). A number of alcohols are tolerated, including both aliphatic (6 examples 39-85%) and aromatic alcohols (9 examples, 59-88%).The aryl amides can also have a range of functional groups including cyano, nitro, alkoxy, and alkyl groups. Picolinic acid derivatives also direct oxidative formation of the ether. 

The difficult problem of introducing bromine into the 2-position in (28) [where R = Me RR = —(CH2)3—] is overcome by brominating the acid (29), then decarboxylating the product by heating with quinoline [29]. If R is alkoxyl or cycloalkoxyl (as in the 1,3-benzodioxole system) the methyl ester (30) must be used, as the free acid is susceptible to decarboxylation under conditions of electrophilic substitution... 

Series of 4-alkoxylated and 4-aminated benzofiiro[2,3]quinoline derivatives was synthesized, evaluated for thdr anti-TB and cytotoxic activities [30], Among the tested compounds, methoxybenzofuro[2,3]quinoline, methylamino-benzofuro[2,3]quinoline, dimethylamino benzofuro [2,3] quinoline, exhibited significant activities against the growth of Mycobacterium tuberculosis (MIC values of <0.20 mg/mL). 

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