Quinoline oxide

The infrared spectra of 2- and 4-hydroxy quinoline 1-oxide have been interpreted to favor forms 55 and 56,. respectively. Lehm-stedt has discussed the tautomerism of 10-hydroxyacridone (57 58) but reached no definite conclusions. Igeta investigated the... 

The photochemical ring enlargement of quinoline 1-oxides provides 3,1-benzoxazepines 1 (see Houben-Weyl, Vol.4/5b, p 12971T).24... 

Irradiation of quinoline 1-oxide itself yields the parent 3,1-benzoxazepine (2), accompanied by quinolin-2(l//)-one (3).17... 

A solution of quinoline 1-oxide (0.29 g, 2 mmol) in cyclohexane (1 L) was dehydrated by azeotropic distillation in the reaction vessel. The solution was purged with dry N2 and irradiated with a Hanau high-pressure Hg lamp. The resulting solution was evaporated and the residue was extracted with a little cyclohexane. The insoluble part contained carbostyril (3). The cyclohexane extract was evaporated and the residue purified by short-path distillation at 50°C/0.1 Torr yield 0.174g (60%) moisture-sensitive oil. 

In the Meisenheimer reaction of quinoline 1-oxides chlorine atoms usually enter the 2-and 4-positions, but not exclusively. 2,4-Dibromoquinoline 1-oxide was 6-chlorinated (57MI1), and the 5- and 6-nitroquinoline 1-oxides were 3-chlorinated to some extent (44JOC302). This reaction with phosphoryl chloride-phosphorus pentachloride has also been used in the preparation of chlorinated phenanthrolines (88YZ1148). 

Kohda, T., Tada, M., Hakura, A., Kasai, H. and Kawazoe, Y. (1987). Formation of 8-hydroxyguanine residues in DNA treated with 4-hydroxyamino quinoline 1-oxide and its related compounds in the presence of seryl-AMP. Biochem. Biophys. Res. Commun. 149, 1141. 

Benzoylation constitutes the first step of the Reissert and Reissert-Henze reactions of quinoline and quinoline 1-oxides respectively, but as the benzoyl intermediates are rarely isolated this topic will be dealt with in Section 2.05.4.7. Pyridine and quinoline N-oxides react easily with p-toluenesulfonyl chloride in pyridine solution to give a variety of products which closely resemble those from the last two reactions discussed (equations 22 and 23). These belong to a family of reactions that have considerable synthetic potential and much mechanistic interest (B-67MI20501) which will be discussed collectively in Section 2.05.4.5. 

Quinoline 1-oxide undergoes nucleophilic attack by ozone to yield a hydroxamic acid (128), and 40% of the starting iV-oxide is recovered (Scheme 74). When an excess of ozone is employed the aldehydes (129) and (130) are obtained. Formation of these products has been attributed to electrophilic attack by ozone rather than further oxidation of (128), because in a separate experiment (128) yielded carbostyril on treatment with ozone. Isoquinoline 2-oxide yields 2-hydroxyisoquinolin-l-one, and acridine 10-oxide gives 10-hydroxyacridone and acridone in a similar manner to the above. Likewise, phenanthridine 5-oxide affords mainly 5-hydroxyphenanthridone. Quinoline 1-oxide undergoes oxidation by lead tetraacetate as shown (Scheme 75). 

The reaction of N,N- dimethylaniline with pyridine (equation 55) should also be considered in this category. Enamines usually attack acylated N- oxides at position 2 unless it is blocked, as in 2-methylquinoline 1-oxide, when attack takes place at C-4. Methyl /3-aminocrotonate attacks quinoline and isoquinoline AT-oxides at the position a to the N- oxide function in the presence of tosyl chloride (78JHC1425). However, pyridine and 2-methylpyridine 1-oxides react at the 4-position (equation 142). A low yield of by-product (242) is formed in each case, probably as a result of self-condensation of methyl /3-aminocrotonate. 4-Hydroxyquinoline 1-oxide is exceptional in that it reacts with an enamine in the presence of tosyl chloride at the /3-position (Scheme 170) (B-71MI20500). 5-Amino-3-methylisoxazole reacts with quinoline 1-oxide at the a-position, and the product can be degraded, to afford ultimately 2-methylquinoline (Scheme 171) (78CPB2759). 

Benzoxazepine intermediates, generated on quinoline 1-oxide photolysis, are more stable than their monocyclic counterparts and therefore they undergo other reactions in preference to the above. Nonetheless, if first isolated they can be induced to isomerize in high yield to /3-hydroxyquinolines. 

Quinoline 1-oxide gives a 4-bromo derivative (Br2-H20,100°C). Isoquinoline 2-oxide is brominated in the 4-position by the mechanism of Scheme 13. 

In the Reissert-Henze reaction, quinoline 1-oxide reacts with benzoyl chloride and potassium cyanide to give 2-cyanoquinoline in good yield (Scheme 30). Pyridine 1-oxides undergo the Reissert-Henze reaction readily when the reaction is carried out in non-aqueous medium using PhCOCl-Me3SiCN (Scheme 31). Pyrimidine /V-oxides and pyrazine /V-oxides also undergo Reissert-Henze reactions. 

The relative reactivity of different positions toward electrophilic substitution is conveniently studied by acid-catalyzed deuterium exchange reaction rates can be followed by NMR and introduction of deuterium hardly affects the reactivity of the remaining positions. In D2S04 both quinoline and quinoline 1-oxide react as the conjugate acid at positions 8 > 5, 6 > 7 > 3. 

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 1-oxide (578) reflects the decrease in intrinsic acidity as the temperature rises, which in turn increases the available amount of free base species. 

Quinoline 1-oxides can be rearranged photochemically into indoles (103 — 104 — 105) or N-hydroxyindoles (106 — 107). Cinnolines are reductively ring-contracted into indoles (Section 3.2.1.6.9.ii). 

Benzoxazepines are obtained photolytically from quinoline 1-oxides (Section 3.2.3.12.5.iv). 

Similar transformations have been reported for quinoline 1-oxide and 3-, 4-, 5-, 6-, 7-, and 8-methylquinoline 1-oxides in aqueous solution,151 for quinoxaline 1-oxide,152 for adenine 1-oxide,153 and for phenanthridine 5-oxide (181 R = H) which yields phenanthridone (182 R = H).154... 

AT-Benzoyl-2-hydroxy-2,3-dihydroindoles (192) are additional products resulting from the photolysis of 2-phenylquinoline 1-oxide (193) and its derivatives in ethanol solution.162 These dihydroindoles are also formed by the solvolysis of the corresponding benz[d]-l,3-oxazepines (194) with aqueous ethanol at room temperature, and are therefore interpreted as arising in this way in the photolysis. Quinoline 1-oxide itself undergoes ring contraction166 to IV-formyl-2-hydroxy-2,3-dihydroindole on irradiation in a protonic solvent. 

The 1,3-dipolar cycloaddition between quinoline-1-oxide (346) and methyl propiolate in the presence of acetic anhydride and hydroquinone gave 348 via 347.390... 

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