Quinolines, alkylation halogenation

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). 

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. 

The reactivities of several azanaphthalene anion-radicals, alter polaro-graphic generation, are discussed by van der Meer.122,123 This includes the radicals of quinazoline and cinnoline whose ESR spectra do not appear to have been reported. The stability of carbon-halogen bonds in various azine anion-radicals, including quinoxaline and quinoline, has been discussed, as has the reactivity of quinoline anions toward alkyl halides.92,182 In the latter reaction alkylation occurs at the 1,2- and 2,4-positions. Heteroarylation of a range of electron-rich substrates by azine anion-radicals has been reported.183 No mechanism is implied in the available abstract, but the apparent electrophilicity on the part of the azine anions is surprising. 

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]. 

Many quinoline derivatives are important biologically active agents. 8-Hydroxyquinoline and some of its halogenated derivatives are used as antiseptics. Chloroquine 111 is one of the older but still important antimalarials. A -Alkyl-4-quinolone-3-carboxylic acid and systems derived therefrom are constituents of antibacterials (gyrase inhibitors [112]) such as nalidixic acid 112, ciprofloxazin 113 and moxifloxazin 114. The quinoline-8-carboxylic acid derivative 115 (quinmerac) is employed as a herbicide for Galium aparine and other broad-leaved weeds. Methoxatin 116, known as coenzyme PQQ is a heterotricyclic mammalian cofactor for lysyl oxidase and dopamine P-hydroxylase [113]. 

The retention characteristics of 29 aza-arenes (e.g., pyridine, acridine, quinoline, benz[a]acridine, and numerous substituted analogs) were studied on a diol column using a 97.5/2.5 iso-octane/ethanol mobile phase [611]. Dimethylbenz[a]acridine was least retained k < 3) and indole had the greatest retention (k > 9). The study also worked with 29 phenols (e.g., numerous alkyl-substituted phenols, nitrophenols, and halogenated phenols). They were studied in detail on the diol column using a 50/50 iso-octane/dichloromethane mobile phase. Appropriate selection of solvent composition provided baseline resolution of isomeric groups (e.g., dimethylphenols using hexane/ethyl acetate). 

The reactivity of ketenimines such as 146 is related to substituent R. Ketenimines were isolable when R was phenyl or alkyl. In contrast, ketenimines wherein R was halogen, thienyl, phenylthio, methylthio, or methylsulfonyl were sufficiently reactive to afford iminoethers (147) at -78°C in the presence of excess lithium methoxide. The trimethyl-chlorosilane-quinoline procedure satisfactorily converted all these substituted iminoethers to amides in good yields. The overall sequence proved amenable for use with cephalosporin acids, by prior protection of the carboxyl group as a silyl ester. Extension of this method to the penicillin series permitted the preparation of 6a-methoxyketenimine 149 and 6a-methoxyimino ether 150 from the corresponding methyl 6p-(2-chlorophenyl)acetamido and fi -dichloroacetamidopenicillanates, respectively. No further transformations of these substances were reported. 

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