Quinolines, alkoxy-, reactions

Quinazoline methiodide, 29 Quinazoline 3-oxides, 31 Quinazoline-thiones, 31, 51 4-Quinazolone, 3-alkyl-, 31 Quindolines, 103, 134, 144, 146 Quindoline-11-carboxylic acid, 144 Quinindoline, 135, 144 Quinolines, alkoxy-, reactions of, 311 2-alkyl-, reaction with carbenes, 77 aza-effects in, 318 basicity of, 244, 245, 247, 288, 289... 

Friedlander synthesis, 2, 445 Quinoline, alkenyl-1,2-dihydro-disproportionation, 2, 369 Quinoline, 2-alkoxy-reactions, 2, 351 Quinoline, 4-alkoxy-reactions, 2, 351 Quinoline, 2-alkoxy-4-hydroxy-synthesis... 

An acid-catalyzed substitution of a 6-oxo group on 2-aminopteridine-4,6-dione with hydrogen chloride in alcohols (65-100°, 3 hr, 80% yield) represents a convenient synthesis of the 6-alkoxy analogs. The reaction proceeds also with pteridine-2,4,6-trione and its 1-methyl and 1,3-dimethyl derivatives. While methoxylation of 2,4,7-trichloro-quinoline gives about equal amounts of 2- and 4-substitution, acid-catalyzed hydrolysis gives specific reaction at the 2-position only. ... 

Indirect deactivation by an alkoxy group is apparent in the sluggish reaction of 4-butoxy-2-chloroquinoline with w-butylamine (EtOH, 5 hr, 180°, but not at 80°). The chloro group in 2-chloro-4-ethoxy-quinoline is more reactive than that in the 4-chloro-2-ethoxy isomer toward alkoxides or amines in spite of the usually more effective para indirect deactivation in the former. For kinetic data on quinolines see Tables X and XI, pp. 336 and 338, respectively. 

Reaction of 2,4,7-trichloroquinoline with sodium methoxide (65°, 30 min) yielded an equal mixture of 2,7-dichloro-4-methoxy- (40%) and 4,7-dichloro-2-methoxy-derivatives (31%). The activating effect of the chloro groups is evident from the inertness of 4-chloro-quinoUne to methoxide ion at 65°. Alteration of the relative reactivity by cationization of the azine ring is again noted here in the acid-catalyzed hydrolysis (dilute HCl, 100°, 1.5 hr) of the trichloro compound to give 72% of the 2-hydroxylation product.Similarly, acid-hydrolysis of the alkoxy group proceeds much more readily in 2-ethoxy-4-chloro- than in 4-ethoxy-2-chloro-quinoline. ... 

Since various substituents are tolerated, the Friedlander reaction is of preparative value for the synthesis of a large variety of quinoline derivatives. The benzene ring may bear for example alkyl, alkoxy, nitro or halogen substituents. Substituents R, R and R" also are variable. The reaction can be carried out with various carbonyl compounds, that contain an enolizable a-methylene group. The reactivity of that group is an important factor for a successful reaction. 

The Reissert-Henze and the Feely-Beavers-Tani reactions are considered together in this section because of their similarity. The former involves cyanation of acyloxy (formed in situ) (Scheme 113), and the latter alkoxy (Scheme 114), quaternary salts. The Reissert-Henze reaction is a facile, fairly general reaction for quinoline and isoquinoline AT-oxides (Table 19) with cyanation occurring a to the ring nitrogen. Certain substituents inhibit reaction, for example a 1-methyl group (equation 125), and others undergo replacement (Scheme 130) (81H(15)98l). Reaction of 1-methylisoquinoline 2-oxide with benzoyl chloride... 

The principal type of ether cleavage classically employed in bisbenzyliso-quinoline alkaloid research is reductive reaction with Na/NH3, which cleaves diphenyl ether linkages, providing characterizable fragments. Numerous examples are to be found in Section II,C. A drawback is that methylenedioxy (e.g., see Section II,C, 131) and certain alkoxy (e.g., see Section II,C, 130) functions are also attacked, leading occasionally to ambiguous results quaternary alkaloids also suffer Hofmanmelimination (e.g., see Section II,C,131). 

Moreover, dioxepin (149) has been prepared by a photochemical reaction of 6-alkoxy-7-(2-oxoalkyl)quinoline-5,8-quinone via intramolecular hydrogen abstraction <93H(36)i477>, and bicyclic 1,3-dioxepin (150) was prepared, and its PE spectra have been studied <95HCA2148>. 

The condensation reaction of aniline with alkoxy-methylenemalonic esters, followed by cyclization to 4-hydroxy-3-carbalkoxy quinolines, is described as the Gould-Jacobs reaction. The reaction can use various derivatives of methylene malonic ester such as keto-malonic esters, malonitriles, malonamides, and Meldrum acid. 

The first catalytic insertion of a C=C bond into an acyl CO bond was attained with Rh catalysts. Thus, the ort/io-substituted olefinic phenol esters with the quinoline chelating group (70) were converted into the )3-alkoxy ketones (72). The stabilization of the intermediate Rh-alkoxide by chelation (71) is a prerequisite for the reaction to occur. 

Quinolines react with arynes and aldehydes in a diastereoselective manner to form benzoxazino quinolines in good yields (Scheme 71) (13OL4620). Halides and alkoxy groups were tolerated on the aromatic aldehydes. Heteroaromatic aldehydes also reacted smoothly (2 examples, 57—69%). The aldehydes can be replaced with ketones without a loss in yield. Various functional groups are also tolerated on the quinoline or aryne. Finally, the reaction proceeds in an analogous fashion with isoquinolines but with less diastereoselectivity (8 examples, 62-92%, 3 1). 

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