2.3- Dihydro quinoline-4-oxides

TMATEMPOI TMDQ 4-Trimethylamino-2,2,6,6-tetra-methylpiperidine oxide iodide 2,2,4-Trimethyl-1,2-dihydro-quinoline Z5MC Zinc-V-pentamethylenedithio- carbamate... 

The nitration of l,2,5-selenadiazolo[3,4-/] quinoline 77 with benzoyl nitrate affords the 8-nitro derivative 78, whereas methylation with methyl iodide or methyl sulfate afforded the corresponding 6-pyridinium methiodide 79 or methosulfate 80, respectively (Scheme 29). The pyridinium salt 80 was submitted to oxidation with potassium hexacyanoferrate and provided 7-oxo-6,7-dihydro derivative 81 or, by reaction of pyridinium salt 79 with phenylmagnesium bromide, the 7-phenyl-6,7-dihydro derivative 82. Nucleophilic substitution of the methiodide 79 with potassium cyanide resulted in the formation of 9-cyano-6,9-dihydroderivative 83, which can be oxidized by iodine to 9-cyano-l,2,5-selenadiazolo [3,4-/]quinoline methiodide 84. All the reactions proceeded in moderate yields (81IJC648). 

Selenium dioxide oxidation of 7,8-dihydro-5(6//)-quinolinone semicarbazone gave, in addition to the expected 4,5-dihydro selenadiazoloquinoline 95 (analogous to sulfur derivative 76), the oxidized l,2,3-selenadiazolo[4,5-/]quinoline 96, which, when heated to 210°C for 30 min, gave the dimeric [l,4]diselenino [2,3-/ 5,6-/ ]diquinoline (95JHC177). 

Ar-quinolin-2-yl)imino]propionates by injection or sublimation at 530°C yielded a mixture of 3-amino- and 3-ethoxy-l//-pyrimido[l,2-rz]quinolin-l-ones <2004AJC577>. An oxidative cascade for the biomimetic formation of the pyoverdine chromophore was supported by incubation of 2-[(4-hydroxyphenyl)- and 2-[(2-(3,4-dihydroxipheny-l)ethyl]-l,4,5,6-tetrahydropyrimidines with polyphenol oxidase or Pseudomonas extract to afford a mixture of 8,9-dihydroxy-2,3-dihydro- and -2,3,5,6-tctrahydro-l //-pyrimido[ 1,2- ]quinolines <20030L2215>. Oxidation of 2-[(2-(3,4-dihydroxiphenyl)ethyl]-l,4,5,6-tetrahydropyrimidine with MnOz gave a similar result. 

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. 

Quinoline homologs and derivatives, including those with double bonds in the side chains, were reduced selectively by catalytic hydrogenation over platinum oxide (side chain double bonds), and to dihydro- and tetrahydro-quinolines by sodium in butanol, by zinc and formic acid, and by triethylam-monium formate [319, 472]. Catalytic hydrogenation of quinoline and its derivatives has been thoroughly reviewed [439]. 

Deoxygenation of N-oxides,4 TiCl4 -NaBH4 (1 2) in DME reduces the N-oxide of pyridine and mcthylpyridines (picolines) to the corresponding heterocycles in high yield. However the N-oxide of quinolines and isoquinolines is reduced further to dihydro derivatives of the hetcrocyclcs. Pyridine, quinoline, and isoquinoline themselves are not reduced by this low-valent titanium species. Reduction of heterocyclic N-oxides with TiCI, has been reported (6, 588). 

A number of furoquinoline alkaloids are available by taking advantage of in-between metalation of 2,4-dimethoxy quinoline derivatives, as established in model studies (Scheme 103). To illustrate, the trimethoxyquino-line 571, upon metalation and ethylene oxide quench, afforded the carbinol 572 which, upon mild hydrolysis, furnished the alkaloid dihydro-y-fagarine (573) together with the quinolone 574 (Scheme 172) (71T1351). 

Oxidation of 2,3-dihydro-l//-pyrimido[l,2-a]quinolines (103) with potassium permanganate yielded 2(3-dihydro-l//-pyrimido[l,2-a]quinolin-3-ones (104) (73YGK313). 

Reissert compounds (l-acyl-l,2-dihydro-2-quinolinecarbonitriles) have been prepared on cross-linked polystyrene and C-alkylated in the presence of strong bases (Entry 8, Table 15.25). Treatment of polystyrene-bound C-alkylated Reissert compounds with KOH leads to the release of isoquinolines into solution (Entry 9, Table 15.25). The reaction of support-bound quinoline- and isoquinoline /Y-oxides with acy-lating agents followed by treatment with electron-rich heteroarenes and enamines has been used to prepare alkylated and arylated derivatives of these heterocycles (Entry 10, Table 15.25 see also Table 15.26). 

This type of synthesis has been described earlier in the formation of 2,3-dihydro-l/7-l,2-diazepino[3,4-A]quinolines by 1,5-dipolar cycloaddition of quinoxalin-4-oxides with 2-chloroacrylonitrile <1996GHEC-II(9)113>. 

In [210, 211] the solid-phase reaction of unsaturated ketones and anilines on a surface of silica gel in the presence of indium chloride under microwave irradiation was described. The library consists of 15 quinolines in yields of 55-87% which were generated quickly and characterized. Ranu et al. [211] showed that dihydro derivatives of qiunolines (e.g., 270 and 273) can also be synthesized, but in this case one component of the reaction must be a 4,4-disubstituted methyl vinyl ketone, for example, mesityl oxide 52 or l-(2-methylcyclopent-l-enyl)ethanone 272 (Scheme 3.75). 

In connection with the anodic intramolecular coupling of 1-benzyltetrahydroiso-quinoline derivatives, the anodic oxidation of 4-(3,4-dimethoxybenzyl)-6,7-dimethoxy-isochromanone 15 has been studied rather extensively. The main product obtained from the isochromanone is a y-lactone, 7a,8-dihydro-3,10,ll-trimethoxy-2 H-phenanthro[9.8a, b]furan-2,7(5 H)-dione 16 13 ... 

The decreasing reactivity of the most familiar aromatic heterocyclic compounds with nucleophilic reagents may be illustrated by the following sequence quinoxaline > acridine > phenanthridine > isoquinoline > quinoline > pyridine. Acridine is alkylated in the 4-position, phenanthridine and quinoxaline in the a-position, isoquinoline in the 1-position, and quinoline and pyridine in the 2- or 4-positions. Weaker nucleophilic reagents seem to enter the 4-position of the pyridine and quinoline rings. If the addition occurs readily and in good yield, the intermediate dihydro derivative may sometimes be isolated otherwise, the product of the subsequent oxidation results. In synthetic work the dihydro derivative is usually directly oxidized. 

Cyclization of the quinoline (242) to give the tetrahydro compound (245) occurred in refluxing AcOH or by treatment of the quinoline (242) with NaOMe in ethanol in the presence of air. Oxidation to yield the dihydro derivative (187) from compound (245) was achieved using LTA <74JMC244>. In a later study, the elaborated quinoline (242) was refluxed in methanolic HC1 to deliver the tetrahydro triazin-3-one (245) (95%). Alternatively, cyclization in refluxing ethanol gave the tetrahydro compound (245) (77%) <76JHC60i>. 

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