Ring of quinolines

There exist many types of azoloquinolines, and therefore it is necessary to define the objects of interest to be described in this review. The tricyclic azoloquinolines reviewed in this article have an azole ring fused to the benzene ring of quinoline (not isoquinoline derivatives) in positions / g, and h. This means that the benzene ring is between azole and pyridine rings, and all of them are ortho-peri condensed. The azole and benzene rings do not have a common heteroatom, and also a carbon... 

Halogen-metal exchange reactions in the carbocyclic rings of quinolines have also successfully been achieved, and all four possible types of lithio... 

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,... 

Almost all alkylations at the carbocyclic rings of quinolines are effected by metal-mediated processes either by quenching of a quinolyl organometallic species with a suitable electrophile or by transition metal-mediated coupling of a haloquinoline or quinolyltriflate with an alkylmetal derivative. 

Nucleophilic substitution most readily occurs at the 2- and 4-position of the more electron-deficient heterocyclic ring of quinolines. However, SNAr reactions at the carbocyclic ring can occur, mainly at positions 5 and 7. 5,7-Dibromo-8-hydroxyquinoline, 5-bromo-8-hydroxyquinoline, and 7-bromo-8-hydroxy-5-methylquinoline undergo conversion to the corresponding chloroquinolines on treatment with neat pyridine hydrochloride at 220 °C in a process that is postulated to proceed via the formation of stabilized Meisenheimer complexes <1996TL6695> (Equations 20 and 21). 

The selective halomercuration and acetoxymercuration of the carbocyclic ring of quinolines can be achieved using mercury salts. However, no new work has occurred in this area since publication of CHEC-II <1996CHEC-II(5)91>. 

The electron-deficient ring of quinoline is not very reactive to electrophilic substitution, the preferred sites of attack being position 5 and 9 [24]. Nitration of CPT (best yields 70 % [25]) gives infacta mixtureofl2-and9-nitrocamptothecin (6). The latter is itself a compound (Rubitecan) endowed with potent antitumor activity [26], and is a precursor of many derivatives, as it can be easily reduced to 9-amino-CPT (7), in turn convertible into 9-hydroxy- and 9-methoxycamptothecin, minor components of the plant extract (Scheme 16.3). 

Compare, for example, the aromaticity index for pyridine versus for the pyridine ring of quinoline. See Matito, E.. Duran, M., and Sola, M. (2005) J. Chem. Phys., 122, 014109. 

The main principle here is that halogen on the homocychc rings of quinoline and isoquinoline, and at the quinoline-3- and the isoquinohne-4 positions, behaves as would a halo-benzene. In contrast, 2- and 4-halo-quinolines and 1-halo-isoquinohnes have the same susceptibility as a- and y-halopyridines (see 8.3.2). 3-Halo-isoquinolines are intermediate in their reactivity to nucleophiles. ... 

Amination of aromatic nitro compounds often occurs smoothly and directly also on condensation with hydroxylamine in alkaline solution, the amino group normally entering ortho or para to the nitro group. One nitro group activates naphthalene derivatives sufficiently, but in the benzene series two are necessary to induce this reaction. 2-Nitro-l-naphthylamine was thus obtained (80%) from 2-nitronaphthalene,400 and 4-nitro-l-naphthyl-amine (60%) from 1-nitronaphthylamine.401 The amino group also enters the nitrated ring of quinoline derivatives. 

Oxidative cleavage of fused heterocyclic systems is often of preparative value. The benzene ring of quinoline, for instance, can be oxidized away,... 

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