Quinolines, halogenated

Halogenated quinolines very often nndergo nncleophilic addition with BuLi, so must be lithiated with LDA or LiTMP " The regioselectivity of their reactions parallels that of the pyridines, and similar halogen migrations are observed (Scheme 116) . ... 

Fig. 3.23 Oxidation of halogenated quinolines to halogenopyridine-2,3-dicarboxylic acids [260]...

The halogenated quinolines include clioquinol (iodo-chlorohydroxyquinohne), diiodohydroxyquinoline, broxy-quinohne, and chlorquinaldol (all rINNs). Once regarded as a prophylactic and remedy for simple diarrhea, some of them remain in limited use for special purposes, notably for the treatment of amebiasis when no alternative is available. 

A major epidemic of subacute myelo-optic neuropathy (SMON) in Japan during 1956-70 was identified as being due to choquinol, which led to the withdrawal of halogenated quinolines in Japan itself and subsequently elsewhere. There is every reason to believe that the adverse effects seen with choquinol can occur with the other hydroxyquinolines, but some of them are still sold freely in various parts of the world (1). 

There was a major epidemic of subacute myelo-optic neuropathy (SMON) in Japan during 1956-70. In 1970 a clinical observation led to case-control and cohort studies, which identified clioquinol as the culprit. A few cases were also reported elsewhere in the world, in Australia (2), Denmark (3), the Netherlands (4), Sweden (5-7), Switzerland (8), the UK (9-11), and the USA (12) some cases involved halogenated quinolines other than clioquinol. Prolonged use of diiodohydroxyquinoline in high doses has been associated with loss of vision and optic atrophy (SED-11, 594) (13). Halogenated quinolines were withdrawn in Japan and the epidemic abated (14). 

Trifluoromethylation reactions of heteroaromatic compounds represent a majority of reported nucleophihc perfluoroalkylations. For example, trifluoromethylation of halogenated quinolines, isoquinolines, or pyridines carried out under pressure using CF3X/CU powder system (X = 1 or Br) in DMF or (Me0)3P=0 solvent affords the corresponding trifluoromethylated heterocycles in 22-60% yield (Fig. 7.21). ... 

Mitamura T, Nomoto A, Sonoda M, Ogawa A (2010) Synthesis of 2-halogenated quinolines by hahde-mediated intramolecular cyclization of o-alkynylaryl isocyanides. Bull Chem Soc Jap 83 822-824... 

Bas M, Gueret C, Perrio C, Lasne M, Barr6 L (2001) Oxidation of 2- and 3-halogenated quinolines an easy access to 5- and 6-halogenopyridine-2,3-dicarboxylic acids. Synthesis... 

It has been stated that many halogen-free compounds, e.g., certain derivatives of pyridine and quinoline, purines, acid amides and cyano compounds, when ignited on copper oxide impart a green colour to the dame, presumably owing to the formation of volatile cuprous cyanide. The test is therefore not always trustworthy. The test is not given by duorides. 

This coupling works best when the halogen at the 7-position is bromine rather than chlorine or fluorine. This represents the first appUcation of this coupling reaction to the intact quinoline nucleus and thus represents an important advance in quinolone chemistry. 

The selectivity of the cyclization using enamino-esters 18-20 derived from m-halogenated anilines 14-16, provided mixtures of 5- and 7-substituted quinolines. In all of these cases, the cyclization gave either equal amounts of the 5- and 7- isomers or in the case of m-iodoaniline, about a 1 2 ratio was observed. During the time of these publications, it was the desire of the authors to obtain the 7-substituted quinolines, which were potential drugs for the treatment of malaria. 

Several 7-substituted (H, halogen, alkoxy, alkylthio, halogen, alkyl, carboxyl) oxazolo[5,4-/i]quinolines were found to be very effective against broadleaf weeds (90EUP1, 90GEP1). 

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