8-Hydroxyquinoline bromination

Coulometric determination of Cu(II) and Ni(II) was canied out applying such reagents as 8-hydroxyquinoline and 8-mercaptoquinoline. Electrogenerated bromine was used as a titrant. 

Hydroxyquinoline forms the complex with Cu(II) in ratio 1 1 at pH 5-7. The composition of the complex is changed on 1 2 at pH>7. 8-Hydroxy-quinoline accepts bromine therefore its excess has been removed with NaOH solution. The complex was extracted with chloroform. It was shown that double extraction was enough to extract the complex. The detection limit is 5x10 M during 10c and at current generation IxlO A. 

Allylation of the 7-hydroxyquinoline derivative 242 with allyl bromide gave the corresponding 7-allyl ether 243 which underwent Claisen rearrangement to give the 8-allyl derivative 244. Acylation and subsequent bromination afforded the dibromopropyl derivative 245. Treatment of 245 with KOH/EtOH gave 8-hydroxypyrroloquinoline 246 that was methylated with methyl iodide to afford 247 (91JOC980) (Scheme 44). 

Discussion. Various metals (e.g. aluminium, iron, copper, zinc, cadmium, nickel, cobalt, manganese, and magnesium) under specified conditions of pH yield well-defined crystalline precipitates with 8-hydroxyquinoline. These precipitates have the general formula M(C9H6ON) , where n is the charge on the metal M ion [see, however, Section 11.11(c)]. Upon treatment of the oxinates with dilute hydrochloric acid, the oxine is liberated. One molecule of oxine reacts with two molecules of bromine to give 5,7-dibromo-8-hydroxyquinoline ... 

Bromine in acetic acid readily converted the activated 3-hydroxy-quinoline into its 4-bromo derivative (76%) under similar conditions 8-hydroxyquinoline gave a mixture of the 5-bromo and 5,7-dibromo compounds [71BAU400 72JOC4078]. All of the possible monobromo derivatives of the latter substrate have been made (91M935). 4-Hydroxy-... 

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... 

Among the most important indirect methods of analysis which employ redox reactions are the bromination procedures for the determination of aromatic amines, phenols, and other compounds which undergo stoichiometric bromine substitution or addition. Bromine may be liberated quantitatively by the acidification of a bromate-bromide solution mixed with the sample. The excess, unreacted bromine can then be determined by reaction with iodide ions to liberate iodine, followed by titration of the iodine with sodium thiosulphate. An interesting extension of the bromination method employs 8-hydroxyquinoline (oxine) to effect a separation of a metal by solvent extraction or precipitation. The metal-oxine complex can then be determined by bromine substitution. 

Diazoxine, a red product which accompanies the formation of 8-methoxy-quinoline from 8-hydroxyquinoline and diazomethane, was first encountered by Caronna and Sansone in 1939. Later, it was suggested that the properties of this product were consistent with structure 189 (R = Me, R = R = H). ° Subsequently, this product has been prepared by treatment of the iodide 190 with potassium carbonate, and the betaine structure has been confirmed by spectroscopic and chemical studies. Compound 189 (R = Me, R = R = H) is isolated as hydrated violet-red needles. The UV and visible spectra are strongly dependent on the nature of the solvent the colors of solutions vary from yellow to blue. Bromination gives the 5,7-dibromo derivative (189 R = Me, R = R = Br), which is also obtained from... 

Complexes of 8-hydroxyquinoline and chromium(III) have been known for many years.1139 Complexes have been mercurated and the deuterated quinoline isolated.1139 The bromination of chelated 8-hydroxyquinoline proceeds about thirty-five times faster than that of the free ligand.1140 Tris(8-hydroxyquinolinato)chromium(III) absorbs large amounts of hydrochloric, hydrobromic and hydrofluoric acids. Chemical reaction with the complex was considered a more likely explanation than solid solution or clathrate formation, even though more than one mole of acid was absorbed per mole of complex.1141... 

Figure 8-3. The bromination of the copper(n) complex of 8-hydroxyquinoline. The sites of bromi-nation are the same as observed in the reactions of the free ligand.

To a suspension of 14.5 g of 8-hydroxyquinoline in 400 ml of water was added dropwise a solution of 32.3 g bromine and 30 g 8% aqueous hydrobromide in 30 ml water. A temperature of reaction mixture decreased to 33°C. Stirring was continued for 30 min, a fine yellow 5,7-dibromo-8-hydroxyquinoline was collected by filtration, washed with water and dried yield 29.8 g (98.4%), melting point 201°C. 

Hydroxyquinolines have been alkylated with methyliodide <94CHC(30)1061> or with various other methylating agents <94H(38)2615>. They have also been brominated <94CHC(31) 176>. 

Albrecht, M., Osetska, O., Klankermayer, J., etal. (2007) Enhancement of near-lR emission by bromine substitution in lanthanide complexes with 2-carboxamide-8-hydroxyquinoline. Chemical Communications, 1834. 

The bromination of 8-hydroxyquinoline (oxine) is applicable to the indirect determination (after separation) of various metals. Each mole of oxine consumes 2 moles of bromine, or 4 equivalents of oxidant ... 

An important example of the use of a bromine substitution reaction is the determination of 8-hydroxyquinoline ... 

In contrast to most bromine substitutions, this reaction takes place rapidly enough in hydrochloric acid solution to make direct titration feasible. The titration of 8-hydroxyquinoline with bromine is particularly significant because the former is an excellent precipitating reagent for cations (see Section 12C-3). For example, aluminum can be determined according to the sequence... 

Very favourable hydrogen bonding may occur in substituted 8-hydroxyquinoline N-oxides (substituted 32) judging from the 50H value (in the 5,7-dinitro-8-quinolinol N-oxide a value of 20.38 ppm is found) as well as the deuterium isotope effects on the C chemical shifts. Complicated substituent effects are found, because substiments such as bromine may interact with both the OH and the N—O group. No tautomerism was observed... 

Fused 2-hydroxyquinoline 29 exists in benzene, chloroform, dioxane, and ethanol in the hydroxy form (81ZOR803). On the addition of water or lower aliphatic carboxylic acids, the oxo form also appears reaching 75% in acetic acid. The introduction of bromine at the 3-position reduces the content of the lactam form in acetic acid to 45%, whereas the introduction of chlorine at position 6 reduces it to 60%. The introduction of the amino group at position 6, however, shifts the equilibrium in the opposite direction. 

Dibromination of the Cu(II), Co(III), Cr(III), Fe(III), and Al(III) chelates of 8-hydroxyquinoline occurred when reacted with bromine in chloroform solution, and the products and yields were comparable to those obtained when the free ligand was brominated. The dichlorination of 8-hydroxyquinoline with chlorine in carbon tetrachloride solution gave a 40% yield, whereas the dichlorination of Cu(II) or Al(III) chelates gave 80-90% yield of 5,7-dichloro-8-hydroxyquinoline. On the basis of this... 

The following example illustrates the manner in which changes that occur in the rate of a ligand reaction upon metal chelate formation can be used for synthetic purposes. Two halogen atoms are introduced into a molecule of 8-hydroxyquinoline rapidly and almost simultaneously to give the 5,7-dihalo derivative (118). Studies on the rate of bromination of the Cr(III) or Cu(II) chelates of 8-hydroxyquinoline showed that mono-bromination in the 5-position occurred extremely rapidly, whereas the subsequent introduction of another bromine atom in the 7-position was quite slow. Advantage was taken of this difference in reaction rates to prepare the 5-bromo-, 5-chloro-, and 5-iodo-substituted compounds of 8-hydroxyquinoline and its 2-methyl and 4-methyl derivatives in good yields (169). 

Scheme 19) (64) starting from 173, an intermediate similar to that which was used in their total synthesis of lavendamycin (Scheme 14) (57). Bromination of the 8-hydroxyquinoline 173, followed by oxidation of the... 

The same method was also used for the synthesis of the anti-malarial compound mefloquine. Heterocyclization of 2-trifluoromethylaniline with trifluoroacetic acid ethyl ester provides 2,8-6w-(trifluoromethyl)-4-hydroxyquinoline. Bromination with phosphorous tribromide, followed a carbon monoxide introduction, affords 2,7-trifluoromethyl-4-carboxylic acid quinoline. Amide formation and pyridine reduction completes the synthesis providing mefloquine in high yields. ... 

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