Oxidation methylquinoline

Treatment of quinoline with ethylene oxide gave oxazolo[3,2-u]quinoline 597 whereas 2-methylquinoline did not react with ethylene oxide (79JOC285). The oxazolidine 597 is labile as monitored by H NMR spectroscopy its colorless solution in CDCI3 became dark red within several hours (Scheme 100). 

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 palladium-catalyzed reaction of benzol]quinoline in the presence of PhI(OAc)2 as an oxidant in MeCN gives an 11 1 mixture of 10-acetoxy- and 10-hydroxybenzo[ ]quinolines in 86% yield (Equation (98)).135 This chelation-directed oxidation can be extended to the benzylic C-H bond of 8-methylquinoline. The inactivated sp3 C-H bonds of oximes and pyridines undergo the same palladium-catalyzed oxidation with PhI(OAc)2 (Equation (99)).1... 

In the case of 8-methylquinoline, the intermediate dihydro derivative yields nearly equal amounts of the two disproportionation products, while with quinoline itself only a trace of the tetrahydro compound was formed. ° In the latter case some other oxidizing agent, perhaps traces of oxygen, must have been involved. 

Epoxidation of propene and oct-l-ene was effected with tran5-Ru(0)j(TMP)/ O ll atm)/water-CH2Cl2. After some 40 turnovers in a day, the deactivated form of the complex, Ru(C0)(TMP).H20 was detected (vide infra). Use of (l-( C)-oct-l-ene suggest that, in part at least, the carbon atom of the Ru(CO)(TMP) formed derives from the first C atom of the octene [591]. For styrene epoxidation by trans-Ru(0)2(TMP)/(LN0)/CgH (LNO=N-oxides of 2,3,5,6-tetramethylpyrazine, acridine, 2-methylquinoline and 3,6-dichloropyridazine) the mono- and bis-A-oxides of tetramethylpyrazine were the most effective co-oxidants [586]. 

For pyridine N- oxides, direct oxygen loss may occur, but for quinoline and isoquinoline N- oxides (118) a 1,2-shift is an alternative, giving the corresponding -one radical cation (119) (68T3139), while -one derivatives themselves readily lose CO, as shown for N-methylquinolin-2-one (120) and acridinone (121) molecular ions (67AJC1179, B-71MS364). 

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). 

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 N-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 N-oxide. When the 8-position is blocked, as in 8-bromoquinoline N-oxide, mercuration is reported to occur at the 4-position (55YZ490, 69CPB906). 

Problem 20.45 Which methylquinoline is vigorously oxidized to a tricarboxylic acid that is then dehydrated to a mixture of two carboxylic acid anhydrides ... 

Gunther and co-workers have developed an exceedingly sensitive colorimetric assay for ethylene oxide based on tho intensely-blne deformed in the presence of lepidine (4-methylquinoline) 9 Other authors/47-274 however, have called attention to certain inadequacies in this method. 

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... 

The photolysis of 2-methylquinoline 1-oxide (185) in aqueous or methanolic solution is equally interesting it affords 3-methyl- (186) and 1-methylquinolin-2-one (187).154... 

A number of other miscellaneous transformations of hetero-aromatic A-oxides have been reported. Of particular interest is the application189 of the photolysis of 2-cyanoquinoline 1-oxides to the synthesis of 1-aminocarbostyrils 2-cyano-4-methylquinoline 1-oxide is converted into the quinolinone by irradiation in dichloromethane solution in the presence of a secondary amine, and the conversion presumably takes place via the intermediate oxaziridine [Eq. (45)]. 

A new approach to the synthesis of 4-alkoxy-l-methyl-2-quinolones has been described (Scheme 3).18 Irradiation of 4-alkoxy-2-methylquinoline 1-oxides (12) (prepared from 2-methyl-4-nitroquinoline 1-oxide) results in photo-rearrangement to give the 2-quinolones (13) as major products a mechanism (Scheme 3) has been proposed. The alkaloids (13 R = Me) and ravenine (13 R = CH2CH=CMe2), which have been synthesized by other means, were prepared in this way. 

Methoxyquinoline is regioselectively oxidized at the methyl group by a chelate-directed palladium-catalyzed C-H bond activation <2004JA2300>. 8-Methylquinoline is selectively oxidized at the methyl position on treatment with palladium(ll) acetate followed by the oxidant phenyliodinium diacetate in acetic acid. The reaction proceeds via formation of a palladacycle (Scheme 4). Performing the reaction in methanol leads to isolation of 8-(methoxy-methyl)quinoline in 77% yield. 

The use of the above methods does not generally result in the coupling reaction of aromatic compounds, ArX, because of the strong bond of C(sp2)-X in ArX. However, the coupling reaction of a cation radical formed from the single-electron oxidation of aromatics readily occurs. For example, 4-methylquinoline coupled to give bis[2-(4-methylquinolyl)] in 90% yield, by electrolysis [14-19]. Direct irradiation (300 nm) of carbonyl compound (13) in dimethylaniline without a solvent gives rise to ethanolamine (14) as the major product as shown in eq. 2.7 [20]. 

The syntheses presented here are examples of two types of "ligand isomers (1) Nitrito complexes, [Ni 2-[(methylamino)-methyl]pyridine 2(ONO)2], and [Ni 2-[(methylamino)methyl]-piperidine)2(ONO)2] (2) Chelating nitrite groups, [Co(2,4,6-trimethylpyridine iV-oxide NCh ], [Co(2,6-dimethylpyridine iV-oxide) 2 (NO 2)2], and [Co(4-methylquinoline iV-oxide)2(N02)2]. 

The chloride complex is made by adding 4.89 g. (0.03 mole) of 4-methylquinoline iV-oxide [obtained by hydrogen peroxide oxidation of 4-methylquinoline (lepidine) (Pierce Chemical Company) by the method of Ochiai11] to a solution of 3.57 g. (0.015 mole) cobalt(II) chloride hexahydrate dissolved in 12 ml. of absolute ethanol. This solution is stirred and then evaporated at a mild temperature on a hot plate. The residue is recrystallized from absolute ethanol, filtered by suction, washed several times with cold ethanol, and then dried in vacuo. Dark blue crystals are obtained which melt between 220 and 222°. Yield is 5.54 g. (84%). Then add 4.8 g. (0.032 mole) of silver nitrite to 2.77 g. (0.008 mole) of Co(4-methylquinoline IV-oxide)2-Cl2 in 800 ml. of dry acetone. The solution is treated as in Procedure 1 on page 204. Brown crystals are obtained from a reddish-brown solution. Yield is 1.15 g. (42%). Anal. Calcd. for C20Hi8CoN4O6 C, 51.18 H, 3.86 N, 11.94. Found C, 50.82 H, 3.94 N, 11.22. 

A recent study of some parameters which influence the oxidation of 2- and 4-methylquinolines to aldehydes with selenium dioxide in dioxane has shown that the successful result of oxidation is dependent on the amount of the oxidant used, but not on its purity, and on neutralization of quinolinecarboxylic acid in the reaction product before isolation of an aldehyde [16]. When 2,2,5,5-tetramethyltetrahydrofuran-3-one (43) was oxidized with selenium dioxide in ethanol, the six-membered selenium-containing heterocycle 44 was formed along with the expected 3,4-furandione 45 [17] (Eq. 5). 

There are a few tetra- and pentacyclic analogues. Benzo analogues of 245 were prepared from pyridine-2,3-dicarboxylic acid anhydride and a tetralin derivative under conditions of the Friedel-Crafts reaction (85JCR(S)338). Pentacyclic compounds 258 (R = H or Me) were prepared from the bis adduct of anthranilic (or IV-methylanthranilic) acid to 1,4-benzoquinone, followed by cyclization in concentrated sulfuric acid (55JCS4440 66CB1991). 6-Methylquinoline-5,8-dione dimerized in the presence of ethanolic N-methyl-cyclohexylamine to 259 in very low yield and the dimerization is interpreted as two base-catalyzed addition reactions and three oxidation steps (71JCS(C)1253). 

Compound 410 was prepared from 4-chloro-3-chloromethyl-5,8-di-methoxy-2-methylquinoline. In hot acetic acid the furan ring was formed and dichromate oxidation gave the product (6SMI1). 

Methylquinoline-3-carboxylic acid is oxidized quantitatively by nickel dioxide in sodium hydroxide after 12 h at 25 °C to quinoline-2,3-dicarboxylic acid [933],... 

There are two possible mechanisms for cyclometallation oxidative addition or electrophilic substitution followed by reductive elimination of a small molecule. The balance of electronic and steric effects determines the course of the reaction. The metallation of 8-methylquinoline is the prototype of most cyclometallation reactions. It can be viewed in two ways, as shown in reactions (ar) and (as). 

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