Quinoline V-oxide

Free-Energy Values (AG°, 0.1 kcal moF ) for the Tautomerism of Some Substituted Oxadiazolo[3,4-/ or [3,4-/i]Quinoline V-Oxides 46... 

Pyridine and quinoline /V-oxides react with phosphorus oxychloride or sulfuryl chloride to form mixtures of the corresponding a- and y-chloropyridines. The reaction sequence involves first formation of a nucleophilic complex (e.g. 270), then attack of chloride ions on this, followed by rearomatization (see also Section 3.2.3.12.5) involving the loss of the /V-oxide oxygen. Treatment of pyridazine 1-oxides with phosphorus oxychloride also results in an a-chlorination with respect to the /V-oxide groups with simultaneous deoxygenation. If the a-position is blocked substitution occurs at the y-position. Thionyl chloride chlorinates the nucleus of certain pyridine carboxylic acids, e.g. picolinic acid — (271), probably by a similar mechanism. 

Quinoline(V-oxide (QuinNO) (13) Bipyridyl bis-Ai -oxide (bipy2NO)... 

Figure 141. Molecular structure of PhiSn(S2CO—i-Pr((quinoline /V-oxide).

Within a given series of heterocycles, differences in reactivity and stability are found compared to their corresponding benzo analogues (see Section 7.02.5). For example, 2,1-benzoisoxazoles are stable in mineral acids, while thieno[3,2-c]isoxazoles (1) and selenolo[3,2-c]isoxazoles (2) are not. Further, 2,1-benzoisoxazoles react with activated methylene synthons to afford quinoline V-oxides <67TL2337> whereas compounds (1) and (2) are inert. The isomer distribution from the pH dependent bromination of thieno[3,2-c]pyrazole (3) is similar to that found for indazole, while thieno[3,2-c]isoxazole (4) is relatively inert <76CS165,77CSi>. 

In other compounds, reaction can occur in both rings. Under such circumstances the orientation can depend on the conditions frequently reaction in the benzene ring involves the cationic species, whereas that in the pyridine ring involves the free base. Thus, the temperature-dependent nitration of quinoline V-oxide 617 reflects the decrease in intrinsic acidity as the temperature rises, which in turn increases the available amount of free base. 

The checkers noticed that a thin film of oil which was evidently quinoline /V-oxide deposited on the surface of the immersion well and irradiation vessel during cooling. 

Quinoline /V-oxide dihydrate is supplied by Aldrich Chemical Company, Inc. and EGA Chemie KG, Steinheim/Albuch, Germany. The submitters prepared the compound by the procedure of Hayashi2 with minor modifications. The water of hydration may be removed under reduced pressure in a drying pistol. However, since the anhydrous N-oxide is very hygroscopic, the submitters have found that it is more expedient to use the dihydrate and remove the water by azeotropic distillation in the irradiation vessel. 

The action of N-oxides of a-dimethylaminocarboxylic acids on dihydroxyphenylborane produces the internal chelates of the oxidation products. Various pyridine and quinoline V-oxides may be used to oxidize organylboranes, but there can be some alkylation of the heteroaromatic rings. ... 

An alternative pattern for functionalization of quinoline-)V-oxides is observed with rhodium and iridium catalysis. The A -oxide functionality can direct the metal insertion to the 2-or the 8-position of the quinoline, and stable five-membered metallocycles can form after C-H insertion at the latter. As... 

Other classes of heterocycles that have been arylated using the C-H activation method and involving palladium acetate and tri-tert-butylphosphonium tetrafluorohorate include the quinoline N-oxides (eq 25) and the thiazoleiV-oxides (eq 26). In the case of quinoline (V-oxides, the regioselectivity of arylation is as expected and leads to the corresponding 2-aryl derivatives. However, in the case of thiazole IV-oxides, the nature of the phosphine has a dramatic influence on the regioselectivity of the arylation process, with tri-terf-butylphosphine providing the product of C5 arylation. 

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