Hydroxy-4-methylquinoline

Conra.d-Limpa.ch-KnorrSynthesis. When a P-keto ester is the carbonyl component of these pathways, two products are possible, and the regiochemistry can be optimized. Aniline reacts with ethyl acetoacetate below 100°C to form 3-anilinocrotonate (14), which is converted to 4-hydroxy-2-methylquinoline [607-67-0] by placing it in a preheated environment at 250°C. If the initial reaction takes place at 160°C, acetoacetanilide (15) forms and can be cyclized with concentrated sulfuric acid to 2-hydroxy-4-methylquinoline [607-66-9] (49). This example of kinetic vs thermodynamic control has been employed in the synthesis of many quinoline derivatives. They are useful as intermediates for the synthesis of chemotherapeutic agents (see Chemotherapeuticsanticancer). 

These early contradictions were eventually resolved and led to the correction by Knorr of his initially proposed structure. While Conrad and Limpach described the reaction of aniline 1 with ethyl acetoacetate 5 which ultimately yielded 4-hydroxy-2-methylquinoline (7) via initial reaction of the amine with the ketone, Knorr described... 

The proposed mechanism for the Conrad-Limpach reaction is shown below. Condensation of an aniline with a 3-keto-ester (i.e., ethyl acetoacetate 5) with loss of water provides enamino-ester 6. Enolization furnishes 10 which undergoes thermal cyclization, analogous to the Gould-Jacobs reaction, via 6n electrocyclization to yield intermediate 11. Compound 11 suffers loss of alcohol followed by tautomerization to give 4-hydroxy-2-methylquinoline 7. An alternative to the proposed formation of 10 is ejection of alcohol from 6 furnishing ketene 13, which then undergoes 671 electrocyclization to provide 12. 

Chloroaniline was reacted with diethyl acetylmalonate at room temperature in vacuo over anhydrous CaCl2 for 10 days. The resulting cro-tonate (803) was cyclized in boiling diphenyl ether for 40 min to give 7-chloro-4-hydroxy-2-methylquinoline-3-carboxylate in 17% yield (73USP3755332). 

Ahematively, the ethoxy group in the ethyl enol ether of acetylacetone (299) was substituted by heating with methyl anthranilate (207) in 1,2-dichlorobenzene to give the enaminone 300. Cyclization of 300 to 3-acetyl-4-hydroxy-2-methylquinoline (301) was catalyzed by sodium methoxide. The corresponding 4-chloro derivative 302 was obtained by heating 301 with phosphoryl chloride. Functionalization of 302 by bromination with A -bromosuccinimide gave 303, which was converted to the desired 3-acetyl-4-chloro-2-cyanomethylquinoline (293) upon treatment with sodium cyanide in dimethylformamide. 

EtOH) was examined in detail by Mead and Koepfli, who, from its reactions and the resemblance of its absorption spectrum to that of 2-hydroxy-6-methoxy-4-methylquinoline, regard it as Z-2 -hydroxyquinine (2 -hydroxy-6 -methoxy-3-vinylruban-9-ol). According to P. B. Marshall, this metabolite is inactive in chick malaria, but Kelsey efaZ. (1946) find that at a dosage of 40-70 mgm./kilo./day, it exercises about the same degree of suppression as 15 mgm./kilo./day of quinine, and quote E. K. Marshall for the observation that it has about one-twentieth the activity of quinine in the malaria of ducks. 

Methylquinoline (2) 3-methyl-2(lH)quinolinone (3) 5,6-dihydro-5,6-dihydroxy-3-me thy 1-2(1 H)quinolinone (4) 6-hydroxy-3 -methyl-2( 1 H)quinolinone (5) 5,6-dihydroxy-3-methyl-2(lH)quinolinone (6) 3-methyl-2,4,6-trihydroxypyridine (1) 4-Methylquinoline (2) 4-methyl-2(lH)quinolinone (3) 7,8-dihydro-7,8-dihydroxy-4-methy 1-2(1 H) quinolinone (4) 8-hydroxy-4-methyl-2(lH)quinolinone (5) 7,8-dihydroxy-4-methyl-2(1 H)quinolinone (6) 6-hydroxy-5-(2-carboxyethenyl)-4-methyl-2( 1 H)pyridone... 

Quinophthalone (6.229) and its derivatives [86] also fall into the methine category, although they appear in the Colour Index under quinoline colouring matters. The parent compound was discovered in 1882 by Jacobsen, who condensed 2-methylquinoline (quinaldine) with phthalic anhydride. The product, quinoline yellow, is used as a solvent dye (Cl Solvent Yellow 33). The light fastness is improved by the presence of a hydroxy group in the quinoline ring system. Derivatives of this type provide greenish yellow disperse dyes for polyester. The moderate sublimation fastness of Cl Disperse Yellow 54 (6.230 R = H) is improved by the introduction of an adjacent bromine atom in Cl Disperse Yellow 64 (6.230 R = Br). 

When the reaction mixture of 4-chloroaniline, triethyl orthoformate, and isopropylidene methylmalonate in Dowtherm A was heated slowly, stirred to reflux, and maintained at reflux for 3 minutes, 6-chloro-4-hydroxy-3-methylquinoline (1167) was obtained (69BRP1147760). 

Hydroxy-2-methylquinoline [826-81-3] M 159.2, m 74-75", b 266-267". Crystd from EtOH or aqueous EtOH. 

There are few dyes in this class but two derivatives are among the most important yellow disperse dyes. The simplest example is Cl Disperse Yellow 54 (62), which is marketed by several companies, as is its brominated derivative Cl Disperse Yellow 64, which has slightly superior fastness properties. The simple molecule may be prepared (B-70MI11203) by condensation between chloroacetone and isatin, followed by fusion of the resulting 3-hydroxy-2-methylquinoline-4-carboxylic acid with phthalic anhydride. 

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