Benzo quinoline-1 -oxide

Benzo[/]quinoline (13 R=H) on nitration at -15 °C gives 7-nitrobenzo[/]quinoline (40%) (13 R = N02) 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 AT-oxide gives 7-nitrobenzo[/]quinoline Af-oxide. 

The Pd-catalyzed oxidation of unfunctionalized C-H bonds has recently been described by Sanford. These reactions lead to the direct, regioselective installation of hydroxyl groups or halogen atoms onto aromatic and heteroaromatic ring systems. For example, benzo[//]quinoline is selectively converted to 10-chlorobenzo[A]quinoline upon treatment with catalytic Pd(OAc)2 and NCS [103]. As shown below, these transformations are also effective for the installation of oxygenated functional groups including acetates and alkyl ethers. The oxidative functionalization of. sy/ C-H bonds has also been achieved [104]. 

Treatment of the Reissert compound derived from 4-chloroisoquinoline with phosphorus pentachloride yielded 4-chloro-l-cyanoisoquinoline. Similar treatment of the benzo[/]quinoline Reissert compound gave a mixture of nitrile and amide." The Reissert compound from 2-bromo-benzo[/]quinoline with thionyl chloride gives 2-bromo-3-cyanobenzo-[/]quinoline." Oxidation of a Reissert compound in the presence of 50% sodium hydroxide and a phase transfer catalyst also gives the isoquinaldonitrile. ... 

Bisalkynylplatinate complexes with the 6, A-chelating benzo[ ]-quinolinate ligand 683 have been prepared by transmetallation of the lithium acetylides with dichloroplatinate. " " The absorption peaks at 392-405 nm are attributed to ligand (acetylide) to ligand (benzoquinolinate) transition. Tris(cycloheptatrienyl)phosphine and diphenyl-phosphine oxide form complexes with two alkynyl ligands at m-positions 684 and 685. " " ... 

The site of dihydroxylation in heterocycles depends on the nature of the heteroaromatic system (Scheme 9.31) usually, electron-rich heterocycles like thiophene are readily biooxidized but give conformationally labile products, vhich may undergo concomitant sulfoxidation [241]. Electron deficient systems are not accepted only pyridone derivatives give corresponding cis-diols [242]. Such a differentiated behavior is also observed for benzo-fused compounds biotransformation of benzo[b] thiophene gives dihydroxylation at the heterocyclic core as major product, while quinoline and other electron-poor systems are oxidized at the homoaromatic core, predominantly [243,244]. 

Mesitonitrile oxide, but not benzonitrile oxide, adds to aza-analogs of phenan-threne, viz., benzo[/z]quinoline, 1,10-, 1,7-, and 4,7-phenanthrolines to give low yields of mono-cycloadducts at the C(5)=C(6> bond. Only 4,7-phenanthroline gave minor products, of which one the bisadduct 167 was isolated in approximately 7% yield. Phenanthridine reacts with two nitrile oxides but affords phenanthridin-6-one rather than a cyclo-adduct (336). 

Reaction conditions used for reduction of acridine [430,476, partly hydrogenated phenanthridine [477 and benzo f]quinoline [477 are shown in Schemes 38-40. Hydrogenation over platinum oxide in trifluoroacetic acid at 3.5 atm reduced only the carbocyclic rings in acridine and benzo[h]quinoline, leaving the pyridine rings intact [471]. 

Oxidation of quinoline and isoquinoline under vigorous conditions with potassium permanganate results in oxidative degradation of the benzo-fused ring and formation of pyridine-2,3- and -3,4-dicarboxylic acid respectively. As expected, the presence of electron-donating substituents facilitates the reaction while electron-withdrawing substituents make oxidation much more difficult. Apart from A-oxide formation, little study has been devoted to the oxidation of other benzo-fused 7r-deficient systems. 

Nitration of pyridines in other than nitric or sulfuric acids is of little interest here because either no reaction or N-nitration takes place (see Section 2.05.2.10). However, pyridine 1-oxide is considerably more reactive and treatment with benzoyl nitrate ultimately leads to the 3-nitro derivative (Scheme 25) (60CPB28). Annelation of a benzene ring bestows greater reactivity on the 3-position in quinoline, compared with pyridine, and reaction with nitric acid in acetic anhydride furnishes the 3-nitro derivative (ca. 6%) (Scheme 26). This isomer has also been obtained, again at low yield (6-10%), by treatment of quinoline with tetranitratotitanium(IV) in carbon tetrachloride (74JCS(P1)1751>. Nitration of benzo analogues of pyridine occurs much more readily in the benzene ring, and Chapter 2.06 should be consulted for these reactions. 

Radical attack on isoquinoline, as either free base or isoquinolinium cation, always occurs at position 1 and the method is not suitable for the preparation of benzo ring-substituted products. The same can be said of radical attack on the JV-oxides of quinoline and isoquinoline. 

Opening of the benzo ring of quinoline can be achieved with a large variety of oxidizing agents. Ozonolysis at -25 °C proceeds by a primary attack at the 5,6- and 7,8-bonds,... 

Whereas with quinoline the benzo ring is the more susceptible to oxidative ring opening, with isoquinoline the matter is more finely balanced. Use of ozone or alkaline permanganate results in attack on both the rings, the products being phthalic acid and pyridine-3,4-dicarboxylic acid (cinchomeronic acid) (38 Scheme 25). 

Benzo ring cleavage of acridine results from oxidation with permanganate, the product being quinoline-2,3-dicarboxylic acid (acridinic acid), which is also the main product of ozonolysis in methanol (Scheme 26) (64JA38). 

Benzo[g]quinolines, e.g. (40), and benzo[g]isoquinolines are oxidized to the corresponding azaanthraquinones using, for example, chromium trioxide in acetic acid (Scheme 28) (79KGS517). 

Permanganate oxidation of the benzo[c]quinolizinium ion (Scheme 35) likewise involves attack of the quinolizinium nucleus to produce quinoline-2-carboxylic acid. Similar behavior is shown by the 10-nitrobenzo[c]quinolizinium ion (71JCS(C)3650). 

Castle and co-workers <1996JHC119, 1996JHC185, 1997JHC1597, 1998JHC1441> used 3-chlorothieno [2,3-3]thiophene-2-carbonyl chloride 280 in the synthesis of the appropriate amides, which by oxidative photo-cyclization gave novel polycyclic heterocyclic ring systems thieno[3, 2 4,5]thieno[2,3-f][l,10]phenanthroline 281, thieno[3, 2 4,5]thieno[2,3-f]naphtho[2,iy ]quinoline 282 and thieno[3, 2 4,5]thieno[2,3-f]naphtho[l,2-g]qui-noline 283, thieno[3, 2 4,5]thieno[2,3-f]naphtho[l,2y ]quinoline 284, thieno[3, 2 4,5]thieno[2,3-f]naphtho[l,2 7]-[l,2,4]triazolo[3,4- ]quinoline 286, thieno[3, 2 4,5]thieno[2,3-f]naphtho[l,2-/]tetrazolo[l,5- ]quinoline 288, benzo[ ]thieno[3, 2 4,5]thieno[2,3-f]quinoline 285, benzo /]thieno[3, 2 4,5]thieno[2,3-f]quinoline 287, benzol/] thieno[3, 2 4,5]thieno[2,3-f]tetrazolo[l,5- ]quinoline 289, and benzo[/jthieno[3, 2 4,5]thieno[2.3-f][l,2,4]triazolo[4,3- ]-quinoline 290. 

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>. 

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