Dicarbonyl compounds quinolines

When we consider the synthesis of a quinoline, the obvious disconnections are, first, the C-N bond in the pyridine ring and, then, the C-C bond that joins the side chain to the benzene ring. We will need a three-carbon (C3) synthon, electrophilic at both ends, which will yield two double bonds after incorporation. The obvious choice is a 1,3-dicarbonyl compound. 0... 

The enamine will normally prefer to adopt the first configuration shown in which cyclization is i not possible, and (perhaps for this reason or perhaps because it is difficult to predict which quinoline will be formed from an unsymmetrical 1,3-dicarbonyl compound) this has not proved a very important quinoline synthesis. We shall describe two more important variants on the same theme, one for quinolines and one for qui nolo lies. 

A microwave-assisted three-component coupling reaction of 5-amino-3-phenyl-pyrazole, a cychc 1,3-dicarbonyl compound and an aromatic aldehyde has been described by Chebanov and co-workers [121]. Depending on the apphed reaction conditions a series of 4-aryl-3-phenyl-l,4,6,7,8,9-hexahydro-l// pyrazolo[3,4-h] quinolin-5-ones 80, 9-p-tolyl-6,6-dimethyl-2-phenyl 5,6,7,9-tetrahydro-pyrazolo [5,l-h]quinazolin-8-ones 81, or 4-aryl-5a-hydroxy-4,5,5a,6,7,8-hexahydropyra-zolo[4,3-c]quinolizin-9-ones 82 can be formed (Scheme 61). 

A variety of reactions that use water as a solvent were also reported. Many of these reports have the advantage of being environmentally friendly. The reaction of Schififbase 97 with 1,3-dicarbonyl compounds 98 in water and catalyzed by benzyltriethylammonium chloride (TEBA) resulted in substituted quinoline derivatives such as 99 in good to high yields (Scheme 27)... 

Quinolines from Aryl-Amines and 1,3-Dicarbonyl Compounds... 

Condensation of a 1,3-dicarbonyl compound with an arylamine gives a high yield of a p-amino-enone, which can then be cyclised with concentrated acid. Mechanistically, the cyclisation step is an electrophilic snbstitntion by the 0-protonated amino-enone, followed by loss of water to give the aromatic quinoline. 

In the first step, p-enaminones 75 or A-arylimines 76 are formed which, after C=0 protonation (possibly by way of an 0-N diprotonated species), undergo intramolecular hydroxyalkylation and dehydration (via 77) to afford quinolines 74. Regioselectivity and product formation in unsymmetrical P-dicarbonyl compounds can be influenced by the acidity of the reaction medium and by the reaction temperature, eg. ... 

An earlier reported synthesis of benzodiazepinoquinolines by reaction of hydrazinobenzo-quinolines with 1,3-dicarbonyl compounds <74BCJ1786> has been shown to be in error the reaction actually affords pyrazolylbenzoquinolines <93BCJ1703>. 

Reactions of heterocycles ch29 How to make pyridazines and pyrazoles How to make pyrimidines from 1,3-dicarbonyl compounds and amidines How to make thiazoles How to make isoxazoles and tetrazoles by 1,3-dipolar cycloadditions The Fischer indole synthesis Making drugs Viagra, sumatriptan, ondansetron, indomethacin How to make quinolines and isoquinolines ... 

X.-S. Wang, M.-M. Zhang, Z.-S. Zeng, D.-Q. Shi, S.-J. Tu, X.-Y. Wei, Z.-M. Zong, Tetrahedron Lett. 2005, 46, 7169-7173. A simple and clean procedure for the synthesis of polyhydroacridine and quinoline derivatives reaction of Schiff base with 1,3-dicarbonyl compounds in aqueous medium. 

Hinsberg suggested calling this series of compounds quinoxalines to point out their relationship with quinolines and the glyoxal—the dicarbonyl compound, from which the first representative of the series was obtained. Quinoxaline [Quin (oline) -I- (gly)oxa/ -l- ine] (Hinsberg 1884). 

In these reactions the tested organic substance and an inorganic salt give a more or less stable strong color due to a complex salt. In Part 2 of this monograph a series of such reactions is described, such as, for example, the reaction of hydroxamic acids with ferric salts (p. 276), the reaction of phenols with ferric chloride (p. 188), the reaction of molybdenum with o-dihydro-xybenzenes (p. 191), of diacetyl dioxime with nickel salts (p. 227), of phenols with Millon s reagent (p. 196), alcohols with ceric ammonium nitrate (p. 170), alcohols with vanadium-hydroxy quinoline complex (p. 171), and the reaction of cis-enols of )5-dicarbonylic compounds and a-dicarbonyl compounds with ferric chloride, (p. 294.)... 

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