4-Hydroxyquinolin-2 -one

Reaction of 4-hydroxyquinoline-2-one 598 with oxalyl chloride gave oxazoloquinoline 599 (970PP211). The oxazoloquinoline 600 was obtained as a byproduct during the synthesis of pyranoquinoline alkaloids 601 by reaction of 598 with 2-methyl-2-chlorobutyne under phase transfer catalysis (87JHC869) (Scheme 101). 

Dimethyl-3 -hydroxydihydropyranoquinolin/4-ones (10, 11) have been obtained from several rutaceous species. Although tracer feeding experiments have not been reported, the co-occurrence of furoquinolin/one and these pyrano derivatives suggest that the biosynthesis of both groups involve oxidative cyclization of a common 3-(2,3-epoxy-3-methybutenyl)-4-hydroxyquinolin-2-one precursor. 

Dimethyldihydropyranoqumolin/4-ones (13, 14) have also been obtained from mtaceous species, but they can be artifacts formed from 3-(3,3-dimethylallyl)-4-hydroxyquinolin-2-one (2) during isolation, by an electrophilic attack involving transfer of a proton to the alkene and the oxygen would be added to the more substituted carbon. 

Once recrystallized, 3-hydroxyquinoline is pure enough for most purposes. One or two more recrystallizations are required to produce white crystals, m.p. 201-202° (cor.). 

Recently, many investigators have extended the early observations that the ultraviolet spectra of - and y-hydroxypyridines resemble those of their A -methyl (not the 0-methyl) derivatives. This spectral resemblance is found both in aqueous solutions and in solutions of solvents with low dielectric constants, e.g., quinol-4-one in benzene, indicating that these compounds exist predominantly in the oxo form under all conditions. These data are summarized in Table I. In contrast, 4-hydroxyquinoline-3-carboxylic acid has been tentatively concluded to exist in the hydroxy form %- pjTid-2-one-4-carboxylic acid has also been formulated as a hydroxy compound, but this has been disputed. ... 

Cyclocondensation of 8-hydroxyquinolin-2(l//)-one and chloroacetone in the presence of K2CO3 in dry DMF at ambient temperature for 24 h afforded 2,3-dihydro-3-hydroxy-3-methyl-5//-pyrido[l,2,3- /e]-l,4-benzoxa-zin-5-one (240, R = Me) (97HCA1161). A tautomeric mixture of ring-opened... 

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 ... 

One frequently used method for synthesizing 2-quinolones is to react anilines with malonic esters. This reaction can be difficult to accomphsh by conventional methods [48,49] since high temperatures (250-350 °C) are required for the generation of an o -oxoketene intermediate 12 (Fig. 6). In a recent example of this type of reaction, Stadler et al. synthesized 4-hydroxyquinolin-2(lH)-ones by using a microwave-assisted procedure (Scheme 5) [50]. 

Substituted phenacyl anthranilates were prepared by reaction of sodium anthranilate with substituted phenacyl halides in DMF. The phenacyl esters were cyclized in polyphosphoric add or by heating to give the respective substituted 2-aryl-3-hydroxyquinoline-4(l. -ones in high yield <95CCC(60)1357>. 

The synthesis of this aminoquinoline starts with one of the standard sequences for preparation of 4-hydroxyquinolines, i.e., with the formation of the Shiff base (5) from the appropriately substituted aniline and diethyl oxaloacetate. Thermal cycliza-tion gives the quinolone (6) this then spontaneously tautomerizes to the enol form (7). Saponification followed by decarboxylation gives the desired quinolol... 

In a molecule of 2-phenyl-l-boraadamantane there are two markedly different types of B-C bonds two of them are boron-alkyl and one is boron-benzyl. On treatment of THF complex 34 with 8-hydroxyquinoline at 20 °C, mpture of the 1-boraadamantane core takes place, resulting in a mixture of boron chelates 52-54 (Scheme 16). When trimethylamine adduct 16 is used as the starting compound, reaction takes place only in boiling toluene. Interestingly, all the products result from the protolysis of B-CH2 bonds only <2006UP1>. 

A one-pot synthesis of pyrano[3,2-c]quinolin-2,5(<5/7)-dione 107 was reported through the condensation reaction of chlorocarbonyl ketenes 108 with 4-hydroxyquinolin-2(l//)-ones 109. This simple procedure was shown to be a convenient synthesis of pharmacologically active compounds in high yields <06S435>. 

Scheme 4.11 Formation of 4-hydroxyquinolin-2-(l H)-ones from anilines and malonic esters.

Ke and Regier [71] have described a direct potentiometric determination of fluoride in seawater after extraction with 8-hydroxyquinoline. This procedure was applied to samples of seawater, fluoridated tap-water, well-water, and effluent from a phosphate reduction plant. Interfering metals, e.g., calcium, magnesium, iron, and aluminium were removed by extraction into a solution of 8-hydroxyquinoline in 2-butoxyethanol-chloroform after addition of glycine-sodium hydroxide buffer solution (pH 10.5 to 10.8). A buffer solution (sodium nitrate-l,2-diamino-cyclohexane-N,N,N. AT-tetra-acetic acid-acetic acid pH 5.5) was then added to adjust the total ionic strength and the fluoride ions were determined by means of a solid membrane fluoride-selective electrode (Orion, model 94-09). Results were in close agreement with and more reproducible than those obtained after distillation [72]. Omission of the extraction led to lower results. Four determinations can be made in one hour. 

Sakamoto [243] determined picomolar levels of cobalt in seawater by flow injection analysis with chemiluminescence detection. In this method flow injection analysis was used to automate the determination of cobalt in seawater by the cobalt-enhanced chemiluminescence oxidation of gallic acid in alkaline hydrogen peroxide. A preconcentration/separation step in the flow injection analysis manifold with an in-line column of immobilised 8-hydroxyquinoline was included to separate the cobalt from alkaline-earth ions. One sample analysis takes 8 min, including the 4-min sample load period. The detection limit is approximately 8 pM. The average standard deviation of replicate analyses at sea of 80 samples was 5%. The method was tested and inter calibrated on samples collected off the California coast. 

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