Quinoline halogens

The Sonogashira reaction can also be applied in quinoline halogens, attaching alkynes the quinoline ring. This method has been employed as an easy way to connect the quinoline pharmacophore tmit in interesting biological molecules as in the derivatization of 2-fluoro-6-0-propargyl-11,12-carbamate ketolide of erythromycin. ... 

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). 

Dialkylquinolinyl boranes 83 and 86 were prepared from halogen/metal exchange of 3-bromoquinoline (70) with n-BuLi followed by quenching with Et2BOMe and Br-9-BBN, respectively. They are then coupled with bromides 84 and 87 to give 3-substituted quinoline derivatives 85 and 88, respectively (85H2375). 

The oxazole ring can be constructed on a quinoline ring such as 589 by alkylation to give 590 which upon treatment with halogen in CHCI3 gave the corresponding oxazoloquinolinium derivative 591 that upon treatment with... 

Since various substituents are tolerated, the Friedlander reaction is of preparative value for the synthesis of a large variety of quinoline derivatives. The benzene ring may bear for example alkyl, alkoxy, nitro or halogen substituents. Substituents R, R and R" also are variable. The reaction can be carried out with various carbonyl compounds, that contain an enolizable a-methylene group. The reactivity of that group is an important factor for a successful reaction. 

Halogenations of quinoline, isoquinoline, acridine, and phenanthridine will be discussed here. Reaction usually occurs in a homocyclic fused ring rather than in the 7r-deficient pyridine moiety, especially in acidic media. Relatively mild conditions suffice, but under more vigorous regimes radical involvement can result in heteroring halogenation. Substituents are able to modify reactivity and regiochemistry. 

Among the nucleophilic processes available for introduction of bromine to quinolines are reactions of the diazonium salts (87JHC181) and syntheses based on hydroxyquinolines or quinolones (91M935) (Scheme 36). The former processes are especially useful for making 5-, 6-, 7-, and 8-bromo derivatives. Halogen-halogen exchange reactions have also been reported, but they are not common. When perfluoroquinoline was heated... 

Halogen exchange with metallic derivatives provides a powerful means of introducing iodine into specific quinoline sites. It has proved possible to prepare 2-, 3-, and 4-iodoquinolines from the trimethylstannyl [82H(19)168] or lithium derivatives [86S670]. Protected 2-aminoquinoline, lithiated at C-3, was quenched with iodine to give a 90% yield of the 3-iodo derivative (86S670). 

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