METHYL-4-HYDROXYQUINOLINE

Submitted by Geobge A. Reykoij s and Chaxles R. Hauser. Checked by Arthur C. Cope and William R. Armstrong. 

2-methyl-4-hydroxyquinoline are separated by filtration. The yield of product, melting at 235-236° (cor.), is 43-46 g. (85-90%). 

Dowtherm is a mixture of diphenyl and diphenyl ether, obtainable from the Dow Chemical Co. 

If the treatment with decolorizing carbon is omitted, the product has a low melting point after several crystallizations. 

The present procedure is a modification of preparations described previously. - - The cyclization has been effected by allowing a solution of ethyl /3-anilinocrotonate in concentrated sulfuric acid to stand at room temperature for several hours by rapidly heating the ester to 240-250° without a solvent or by adding the ester to mineral oil at 250°. The procedure described has been applied to the preparation of other 2-sub-stituted 4-hydroxyquinoline derivatives.  

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Recently kinetic data have become available for the nitration in sulphuric acid of some of these hydroxy compounds (table 10.3). For 4-hydroxyquinoline and 4-methoxyquinoline the results verify the early conclusions regarding the nature of the substrate being nitrated in sulphuric acid. Plots of log Q against — (Lf + logioflHao) fo " these compounds and for i-methyl-4-quinolone have slopes of i-o, i-o and 0-97 at 25 C respectively, in accord with nitration via the majority species ( 8.2) which is in each case the corresponding cation of the type (iv). At a given acidity the similarity of the observed second-order rate constants for the nitrations of the quinolones and 4-methoxy-quinoline at 25 °C supports the view that similarly constructed cations are involved. Application of the encounter criterion eliminates the possibilities of a... 

The case of i-methyl-4-quinolone is puzzling. The large proportion of the 3-nitro isomer formed in the nitration (table 10.3 cf. 4-hydroxyquinoline) might be a result of nitration via the free base but this is not substantiated by the acidity dependence of the rate of nitration or by the Arrhenius parameters. From r-methyl-4-quinolone the total yield of nitro-compounds was not high (table ro.3). 

In acidic solution, the degradation results in the formation of furfural, furfuryl alcohol, 2-furoic acid, 3-hydroxyfurfural, furoin, 2-methyl-3,8-dihydroxychroman, ethylglyoxal, and several condensation products (36). Many metals, especially copper, cataly2e the oxidation of L-ascorbic acid. Oxalic acid and copper form a chelate complex which prevents the ascorbic acid-copper-complex formation and therefore oxalic acid inhibits effectively the oxidation of L-ascorbic acid. L-Ascorbic acid can also be stabilized with metaphosphoric acid, amino acids, 8-hydroxyquinoline, glycols, sugars, and trichloracetic acid (38). Another catalytic reaction which accounts for loss of L-ascorbic acid occurs with enzymes, eg, L-ascorbic acid oxidase, a copper protein-containing enzyme. 

Dichloro-2-methyl-8-hydroxyquinoline (5,7-dichloro-8-hydroxyquinaldine) [72-80-0] M 228.1, m 114-115°, pKE,t(i) Crystd from EtOH. 

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. ... 

A series of 2-aryloxazolo[4,5-/i]quinoline-5-arylidines was prepared by the reaction of 5,7-diamino-8-hydroxyquinoline with aromatic or aliphatic aldehydes in the presence of a basic catalyst such as piperidine. On the other hand, 2-styryl-5-diacetylamino-oxazolo[4,5-/i]quinolines were prepared by interaction of 2-methyl-5-diacetylamino-oxazolo[4,5-/i]quinoline with aromatic aldehydes (77MI1, 82MI2) (Scheme 6). 

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). 

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). 

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... 

The five-coordinate complexes Ir(CO)(PPh3)2L, where HL = /3-diketone, A-benzoyl-A-phenyl-hydroxylamine, salicylaldehyde, 8-hydroxyquinoline, 2-hydroxybenzophenone, 2-hydroxy-8-methoxybenzophenone, were prepared from [Ir(CO)(PPh3)2Cl].632 The resulting compounds all underwent oxidative addition reactions with Br2. Reaction of [(cod)2IrCl]2 with N-substituted 3-hydroxy-2-methyl-4-pyridine gives the bichelated complex (389). 33... 

GFP hopo ICBP IP3 Ln3+ mal memal MLCK nota oxine par pdta pmea py quin-2 green fluorescent protein hydroxypyridinon(at)e intestinal calcium-binding protein inositol 1,4,5-triphosphate a lanthanide(III) cation malonate methylmalonate myosin light chain kinase 1,4,7-triazacyclononane-l,4,7-triacetate 8- hydroxyquinoline pyridine-2-azo-4 -dimethylaniline propylene-1,2-diaminetetraacetate 9- [2-(phosphonomethoxy)ethyl] adenine pjrridine pjrridyl 8-amino-2- [(2-amino-5-methylphenoxy )methyl] -6-methoxyquinoline-ATJV -tetraacetate 2- [ [2-[his(carboxymethyl)amino]-5-methyl-phenoxy] methyl] -6-methoxy-8- [bis(carboxymethyl) amino] quinoline]... 

Atomic absorption spectrometry coupled with solvent extraction of iron complexes has been used to determine down to 0.5 pg/1 iron in seawater [354, 355]. Hiire [354] extracted iron as its 8-hydroxyquinoline complex. The sample is buffered to pH 3-6 and extracted with a 0.1 % methyl isobutyl ketone solution of 8-hydroxyquinoline. The extraction is aspirated into an air-acetylene flame and evaluated at 248.3 nm. 

Methyl-8-hydroxyquinoline, 7 588 10-Methyl-9-acridinium carboxylate, chemiluminescence reagent, 5 846 Methyl abietate, 24 553 Methyl acetate... 

Methyl 2-substituted 4-hydroxyquinoline-3-carboxylates (564) were prepared in 41 -54% yields by heating diazo derivatives (562) in boiling toluene for 0.5-9 hr, via aminomethylenemalonates (563). H-NMR investigation revealed the formation of a 52 48 mixture of aminomethylenemalonate (563, R = COPh) and quinolinecarboxylate (564, R = COPh) when the diazo compound (562, R = COPh) was heated in toluene for 4 hr. A better yield was achieved when the triester (562, R = COOMe) was heated in boiling 1,2-dichlorobenzene (80T1821). 

Dimethyl methyithio(phenylamino)methylenemalonate was cyclized in boiling decalin for 2 hr to afford methyl 2-methylthio-4-hydroxyquinoline-3-carboxylate in 70% yield (69T4649). 

The prothoracic defensive secretion in one of water beetles, llybius fer-nestratus, contains as a main component methyl 8-hydroxyquinoline-2-carboxy-late (51) (Table V), which is not toxic to amphibians and fishes but produces clonic spasms in small mammals like mice (96,100,101). 

A predominant toxin (51) from water beetles of the genus llybius (Table V) shows a UV absorption corresponding to hydroxyquinoline or hydroxyiso-quinoline. The H-NMR spectrum exhibits, beside signals of methyl ester and phenol, signals of five aromatic protons as both ABC and AB systems, the latter indicating two protons at C-3 and C-4 in quinoline. Since electron pyrolysis of 51 gives radioactive 8-hydroxyquinoline, its structure is identified as methyl 8-hydroxyquinoline-2-carboxylate (51) and confirmed by synthesis from xanthurenic acid (52) (Scheme 48) (101). The precursor of this alkaloid was shown to be tryptophan (444). 

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