Quinolines jV-oxides

Th(CIJCC02)4-2L Th (02CCH2)20 2-3L-3H20 Th(N03)4-3C8H11N0 L - quinoline JV-oxide ThX4yL... 

Hydroxyamino)quinoline JV-oxide is a carcinogen which is oxidized to give different radicals in different conditions. A structure, unlikely in the author s view, has been assigned to one. Conceivably, a nitroxyl-containing structure is involved here.392,393... 

Ochiai and Ohta have used lead tetraacetate in benzene to convert aromatic iV-oxides (67) to the corresponding acetylated hydroxamic acids (68). Similar oxidation of quinoline and isoquinoline JV-oxides... 

Radical attack on isoquinoline, as either free base or isoquinolinium cation, always occurs at position 1 and the method is not suitable for the preparation of benzo ring-substituted products. The same can be said of radical attack on the JV-oxides of quinoline and isoquinoline. 

The first reduction wave for phenanthridine jV-oxide in dimethyl-formamide (at 25°) appears at — 1.774 (vs. s.c.e.) in good agreement with the HMO energy of the lowest vacant orbital277 a mechanism for the reduction has been proposed.278 No esr signal could be detected during controlled-potential electrolysis at the appropriate potential, perhaps because of the relative instability of the anion radical. This behavior, which is paralleled by isoquinoline, contrasts sharply with that of the oxides of other polynuclear N-heteroaromatic systems (e.g., quinoline and acridine).277... 

Mercuration of quinoline N-oxide in acetic acid or perchloric acid gives the 8-mercurio-chloride (26) as the main product and small amounts of the 3-, 5-, 6- and 7-isomers. In the absence of solvent mercury(II) sulfate gives all the possible isomers although the total yield is poor. 6-Methylquinoline JV-oxide gives the 8-substituted derivative (27). The preferential 8-orientation is accounted for in terms of preliminary coordination of the mercury atom at the oxygen of the JV-oxide. When the 8-position is blocked, as in 8-bromoquinoline N-oxide, mercuration is reported to occur at the 4-position (55YZ490, 69CPB906). 

On treatment of both quinoline and pyridine /V-oxides with bromine and thallium(iil) acetate, y-bromo-derivatives are formed pyridine JV-oxides are the less reactive substrates/ The reaction of 8-methoxyquinoline iV-oxide with acetic anhydride and methanol yields 84% of 2,8-dimethoxyquinoline. Similarly, the reaction of the 6-methoxy-iV-oxide and ethanol and acetic anhydride gives 2-ethoxy-6-methoxyquinoline, but, under the same conditions, the 7-methoxy-N-oxide is unchanged/ The Reissert compounds (149) derived from substituted quinolines, on treatment with thallium(lll) nitrate and trimethyl orthoformate, undergo either smooth ring-contraction or oxidative debenzoyl-ation, depending on the substitution pattern in the aromatic ring (Scheme 61)/ ... 

Methylation. The reaction of 1,10-phenanthroline-JV-oxide with methylsulfinyl carbanion has been reported. Liberation of the A oxide moiety occurred when the compound was treated with sodium hydride in dimethylsulfoxide for 0.5 h, resulting in the formation of benzo[A]quinoline as a sole product in 48% yield. Prolonging the reaction time to 4 h led to a mixture of three products corresponding to further methylation at the 5- and 6-positions of the quinoline ring (eq 4). ... 

The JV-oxidation of 3-chloropyridazines increases their reactivity toward methoxide and sulfanilamide anions. The reactivity of 4-chloro- or 4-nitro-quinoline and of chloropyridines toward methoxide ion and piperidine is less than that of the corresponding N-oxides (see Tables II and XI, pp. 270 and 338). The activating effect of the AT-oxide moiety in 3-halopyridine AT-oxides is greater than that of a nitro group, and in fluoroquinoline AT-oxides the activation is transmitted to resonance-activated positions in the adjoining rings. ... 

Previous reports have indicated that 2-phenylquinoline A-oxide nitrates at the 4-position. However, it is now clear, although for reasons not yet understood, that the site of nitration varies with the reaction conditions. For example, 2-(3-nitrophenyl)quinoline iV-oxide is always produced, albeit in variable yield (27— 78%), in 80— 95% sulphuric acid regardless of the reaction temperature. In contrast, 4-nitro-2-phenylquinoline JV-oxide is the main product (19—35%) in more dilute (70—75%) sulphuric acid. N-Amino-quinolinium, -isoquinolinium, and -phenanthridinium salts, with base, give not the anticipated N-imides but their dimers, e.g. (106). ° Despite the fact that the 7V-imide monomers cannot be... 

Further extensions of the slilbene photocydizatinn are seen in analogous reactions of compounds containing the imine chro-mophore (e.g. 3,71 or an amide group (3.72). The amide reaction can be considered formally as giving a zwitterion intermediate, which undergoes proton shifts and oxidation to form the observed product. Non-oxidative cyclizations that start with either JV-vinyl aromatic carboxamides (C=C—N—CO—Ar) or N-aryl a. -unsaturated carboxamides (Ar—N—CO—C—C) have been extensively used to make quinoline or isoquinoline alkaloids and their derivatives a fairly simple example is given in (3.73). 

Treatment of the 2-pyrrolyl allyl thioether (498) with acetic anhydride and quinoline at 170 °C (or in A jV-dimethylaniline at ca. 100 °C) results in a thio-Claisen rearrangement to give the 5-(3-allyl-2-pyrrolyl) thioacetate (499), whilst peracid oxidation of (498) produces the non-rearranged sulfone in low yield and Raney nickel reduction of (498) yields 3-propylpyrrole (78CJC221). The polyphosphoric acid-catalyzed cyclization of (2-pyrrolylthio) acetic acid (501 R = R = H) somewhat unexpectedly yields (502) via the Spiro intermediate, instead of forming the expected oxothiolane (500), which can be obtained by a Dieckmann cyclization of ethyl (3-ethoxycarbonyl-2-pyrrolylthio) acetate (501 R = Et, R = C02Et) (B-77MI30506). 

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