Synthesis of Quinoline Derivatives

Cacchi and Palmier (83T3373) investigated a new entry into the quinoline skeleton by palladium-catalyzed Michael-type reactions. They found that phenyl mercurial 134 was a useful intermediate for the synthesis of quinoline derivatives, and that by selecting the reaction conditions the oxidation level of the heterocyclic ring in the quinoline skeleton can be varied. On such example is shown in Scheme 16. PdCla-catalyzed coupling between organomercurial reagent 134 and enone 135 delivered adduct 136 which was subsequently cyclized to quinoline 137 under acidic conditions. 

Conrad, M. Limpach, L. Ber. Dtsch. Chem. Ges. 1887, 20, 944. Max Conrad (1848—1920), born in Munich, Germany, was a professor of the University of Wiirz-burg, where he collaborated with Leonhard Lhnpach (1852—1933) on the synthesis of quinoline derivatives. 

Makioka Y, Shindo T, Taniguchi Y, Takaki K, Fujiwara Y (1995) Ytterbium(III) triflate catalyzed synthesis of quinolinic derivatives from V-arylaldimincs and vinyl ethers. Synthesis 801-804... 

Friedlander Hetero-Annulation for the Synthesis of Quinoline Derivatives... 251... 

Another example of utilizing the amino group of 5-aminotetrazole in medicinal chemistry is the synthesis of quinoline derivative 411 as a potential antidiabetic agent (Equation 73) <2000BML1831>. 

Scheme 2 Synthesis of quinoline derivatives by [4 + 2] cycloaddition reaction [8]...

Scheme 22 Synthesis of quinoline derivatives, valuable intermediates for the pte paration of herbiades (Ref 19)...

Combes, A. Synthesis of quinoline derivatives from acetyl acetone. Bull. Soc. Chim. France 1883, 49, 89. 

Conrad, M., Limpach, L. The synthesis of quinoline derivatives from acetoacetic ester. Ber. 1887, 20, 944-948. 

Fiorito J, Saeed F, Zhang H, Staniszewski A, Feng Y, Francis YI et al (2013) Synthesis of quinoline derivatives Discovery of a potent and selective phosphodiesterase 5 inhibitor for the treatment of Alzheimer s disease. Eur J Med Chem 60 285-294... 

The synthesis of quinoline derivatives using metal catalyzed processes continues to be of interest. A modified preparation of 2,3-dialkylquinolines was reported <04JHC423> from nitroarenes and tetraalkylammonium halides via an in situ ruthenium-catalyzed reduction followed by an intrinsic amine exchange reaction using tin(ll) chloride. One of the examples reported is shown below in Scheme 25. 

A method was developed for the synthesis of quinoline derivatives from isatoic anhydrides and lactones. The amino ketones formed at the first stage were then converted into the desired products by cyclocondensation after isolation or by direct heating of the reaction mass. Thus, the reaction of the anhydride 2 with the butyrolactones 94 in the presence of lithium diisopropylamide gave the amino ketones (95) (yield 99%), which when boiled in toluene gave 4-hydroxy-3-R-l-methyl-2-quinolones 96 (yield 98% with R = H or 70% with R = Me). It was established that the latter exist in two isomeric forms 96a,b [57],... 

Various other cyclization protocols for the synthesis of quinoline derivatives were reported in 2001. Functionalized 3-formylquinolines were prepared by condensation of functionalized anilines such as 60 and vinamidinium salt 61. Subsequent cyclization and hydrolysis afforded... 

Hosseini-Sarvaria (2011b) reported the synthesis of quinoline derivatives (60) by the condensation of 2-aminoaryl ketones (58) with methylene carbonyl compounds (59) catalyzed by nanoflake ZnO as a reusable heterogeneous catalyst under solvent-free conditions involving Friedlander heteroannulation (Scheme 9.14). The employed catalyst was synthesized from zinc acetate dihydrate and urea. It constitutes a simple, environmentally benign, and cost-effective method for the synthesis of quinolines. Tamaddon and Moradi (2013) reported the application of nano-ZnO as a reusable heterogeneous catalyst for the synthesis of Biginelli dihydropyrimidines... 

SCHEME 13.92 Synthesis of quinoline derivatives 442 by AgNO catalysis. 

Scheme 3.32 Synthesis of quinoline derivatives using green method...

Wang et al. utilized /t-TSA as the catalyst to demonstrate the synthesis of quinoline derivatives (78) under solvent-less condition They carried out their reaction both under MW and conventional heating. Although yields of the products were excellent under both conditions, the reaction accomplished in the influence of MW was reported to be completed within a few seconds (Scheme 6.31) [70]. 

Synthesis of quinoline derivatives via the Friedlander coupling condensation reaction [116] was carried out under microwave inadiatioa The reactants were different acetophenones and 2-aminoacetophenones or benzophenones. The product was obtained in 4 min of irradiation (Scheme 11.59). 

Copper(I) chloride can be an effective catalyst in multicomponent reactions, such as in the synthesis of 5-alkoxycarbonyl-4-aryl-3,4-dihydrop3nimidine-2-(l//)-ones, the synthesis of quinoline derivatives (eq 69), and the synthesis of fully substituted triazoles. The use of CuCl as an additive is also reported in cross-metathesis reactions leading to significant turnover enhancement. ... 

Quinoline derivatives are of wide occurrence in natural products and medicinal drugs they also find applications in polymer chemistry, electronics, and optoelectronics for their excellent mechanical properties as well [200]. The Friedlander synthesis of quinolines is a classic method involving reduction of o-nitro aryl aldehyde as the first step followed by condensation of the reduced product with enolizable carbonyl compound in the presence of a Bronsted or Lewis acid catalyst [201]. To avoid the harsh reaction conditions, the use of ILs has recently gained considerable attention in the synthesis of quinoline derivatives. 

Scheme 10.3 Co2(CO)g-catalyzed synthesis of quinoline derivatives from N,Af-diallylaniline (a) and from N-benzylideneaniline and AflV-diallylaniline (b).

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