Quinoline A -oxides

In the A-oxides 46 the tautomerism of the oxygen atom attached to the oxadiazole nucleus was determined as AG 20 kcal moF The steric effect of the 9-methyl group of 7,9-dimethyl l,2,5-oxadiazolo[3,4-/]quinoline A-oxide 46, (Y = C—CH3 X = N = H = CH3) would not be expected to favor the presence... 

Unlike quinoline A -oxide, which yields a mixture of quinolin-2(l//)-one and 4-(4-quinolyl)quinolin-2(l//)-one, 7-methoxy-4-phenylquinoline A -oxide (47) with phenylsulfonyl chloride and dimcthylsulfoxonium metliylide affords the l//-l-benzazepine 48 (a rare example of an 7V-unsubstituted l//-l-benzazepine), together with small amounts of the dimeric 1//-1-benzazepine 49 and 2,2-bis(7-methoxy-4-pheny]-2-quinolyl) (8% mp 276 C).166... 

Other quinoline A-oxide derivatives have been examined. A 1,3-oxazepine is the major product of irradiation of 2-cyanoquinoline A-oxide whereas lactam formation predominates on irradiation of 4-methylquinoline N-oxide in aqueous ethanol.60 Lactam formation has been shown to be influenced by an external magnetic field and on this basis it has been proposed that the first step in this transformation is the formation of an excited radical-ion pair.61 1,3-Oxazepines undergo further reaction on prolonged irradiation. The synthesis of 4-substituted indoles, for example, has been accomplished in this way by irradiation of 5-substituted quinoline A-oxides.62... 

The Sn atom in the quinoline-N-oxide derivative (Table 26, entry 7) shows trans-C3Sn02 TBP coordination [SC-Sn-C 357.5°, O - Sn-O 171.4°417], but the O - Sn bond of 2.446 A is much longer than that (2.319 A) found in the quinoline A-oxide complex of the benzisothiazolone derivative (entry 2)414. 

Thienoisoquinolines can be prepared in high yields by the palladium cross-coupling reaction of o-formylarylboronic acids with aryl halides. By this method, thieno[3,2-c]- (102), thieno[3,4-c]-(103), and thieno[2,3-c]isoquinolines (104) have been prepared in yields of 90%, 52%, and 75%, respectively (Scheme 48) <86CS3il, 89JHC865). This method was unsuccessful for the preparation of thieno[3,2-c]quinoline A-oxide and thieno[3,2-c]isoquinoline A-oxide. The former compounds were readily prepared via a modification of the reaction using a palladium-catalyzed coupling reaction between 2-tributylstannyl-3-thiophenecarboxaldehyde and o-bromonitrobenzene, while the isoquinoline A-oxide was prepared by mcpba oxidation of the parent compound <90JHC1127>. 

Quinoline A -oxide gives a 4-bromo derivative (Br2H20, 100 C). Isoquinoline A -oxide is brominated at the 4-position... 

In the ReissertHenze reaction, quinoline A-oxide reacts with benzoyl chloride and potassium cyanide to give 2-cyanoquinoline in good yield (Scheme 42). Pyridine 1-oxides undergo the ReissertHenze reaction readily when the reaction is carried out in nonaqueous medium using PhCOClMe3SiCN (Scheme 43). Pyrimidine A-oxides and pyrazine A-oxides also undergo ReissertHenze reactions. 

The preparation of 3,1-benzoxazepines by photochemical isomerization of quinoline A-oxides constitutes a rather general entry into this class of seven-membered heterocycles. Since the structure of the photoisomer of 2-phenylquinoline A-oxide was first recognized as 2-pheny 1-3,1-benzoxazepine by Buchardt et al.,3 the scope of this method for oxidative ring expansion of six-membered heterocyclic A-oxides to 1,3-oxazepines has been extensively explored.4 For example, irradiation of 2-cyano-, 2-phenyl-, and 2-methoxyquinoline A-oxides affords the corresponding 2-substituted 3,1-benzoxazepines in 70-90% yield.5 However, isolation of the moisture-sensitive parent compound was only recently accomplished in the submitters laboratories.6... 

Benzo[/]quinoline (13 R=H) on nitration at -15 °C gives 7-nitrobenzo[/]quinoline (40%) (13 R = NO2) together with smaller amounts of the 10- (13%) and 9-nitro derivatives (9%). At 0 °C the 7,9-dinitro derivative is obtained. Nitration of benzo[/]quinoline A-oxide gives 7-nitrobenzo[/]quinoline A-oxide. 

Asymmetric intermolecular Pauson Khand reactions have been reahzed using a number of chiral auxiliaries chelating to the metal and/or attached to the alkyne. One example using a camphor-derived hgand is seen in Scheme 253. Moderate asymmetric induction has been observed using chiral amine A-oxides as the promoter. For example, (-F)-indohzino[3,4-b]quinoline A-oxide gave up to 53% ee. 

Quinoline A-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 Hayashi 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. 

P3Tidine N < benzene C—NO2 < pyridine N—0 < pyridine N—CHg for these activating centers. The same relationship quinoline ring-A < naphthalene C—NO 2 < quinoline A-oxide holds for the 4-halo bicyclic compounds in Table XI and for fluoro-quinolines and -pyridines. ... 

The reaction of zirconyl perchlorate with pyridine iV -oxide in ethanol (382) gave a product of composition Zr0(py0)e(C104)2. The infrared spectrum shows that bonding is through the oxygen. A similar product was obtained with quinoline A -oxide (327). Zirconium is assumed to have a coordination number of seven in these species. The nature of the zirconium-oxygen moiety is not known. 

Af-Oxide chemistry in these bicyclic systems largely parallels the processes described for pyridine 7V-oxide, with the additional possibility of benzene ring electrophilic susbstitution, for example mixed acid nitration of quinoline A -oxide takes place at C-5 and C-8 via the O-protonated species, but at C-4 at lower acid strength nitration of isoquinoline A/ -oxide takes place at C-5. ... 

Quinoline A -oxide (QuinNO) (13) Bipyridyl bis-A-oxide (bipy2NO)... 

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