Quinolines Knoevenagel reaction

Besides the domino Michael/SN processes, domino Michael/Knoevenagel reactions have also been used. Thus, Obrecht, Filippone and Santeusanio employed this type of process for the assembly of highly substituted thiophenes [102] and pyrroles [103]. Marinelli and colleagues have reported on the synthesis of various 2,4-disubstituted quinolines [104] and [l,8]naphthyridines [105] by means of a domino Michael addition/imine cyclization. Related di- and tetrahydroquinolines were prepared by a domino Michael addition/aldol condensation described by the Hamada group [106]. A recent example of a domino Michael/aldol condensation process has been reported by Brase and coworkers [107], by which substituted tetrahydroxan-thenes 2-186 were prepared from salicylic aldehydes 2-184 and cycloenones 2-185 (Scheme 2.43). 

The Winterfeldt oxidation (O2, r-BuOK) of carbolines such as the unsubstituted (37a) and aryl (37b) (Scheme 13) is known to give the pyrrolo[3,4-( ]quinoline-9-ones (38), via the attack on the amide function by the ketone enolate (path a). In the presence of the ester functionality (37c), however, the more readily formed malonic-type anion attacks the ketone according to an intramolecular Knoevenagel reaction leading to the new pyrrolo[2,3-c]quinoline-4-one system (39) (path... 

In this stndy 5-(Quinoline-2-ylidene)-l,3-diethyl-2-thiobaibituric acid have been synthesized via Knoevenagel condensation reaction, the prodnct solntions were prepared 10 -10 M in CHCIj, THF, MeOH, DMF and DMSO. UVAfiS spectra recorded and then compared at each other. Absorbance of the solntions were measured at 200-300 nm. The maximum absorbance valne increased and a new absorption appeared at 400-500 nm. The samples were excited at 337 nm in order to measure fluorescence. The maximum emission was observed in MeOH at 398 nm. These values increased by time therefore, the samples were not stable in solution state. 

Chloro-3-fonnylquinolines 161 (Scheme 31) were transformed in the presence of acetic acid to 3-formylquinolones which upon reaction with acetophenones provided the intermediate a,p unsaturated Knoevenagel adducts. Subsequent Krohnke reaction of these adducts with pyridinium salts 162 and ammonium acetate provided the final quinoline-pyridines 163 in excellent yields [68]. All the compounds were tested... 

The Knoevenagel condensation of alkyl orilio-nitroaiylacetates and ortho-nitroarylacetonitriles with aliphatic aldehydes proved to give the corresponding alkylidene nitriles and esters [191-194]. In the presence of a base these nitriles undergo cyclization into indole or quinoline derivatives, depending on the reaction... 

Other reactions that have been applied in the Ugi postmodification strategy are the aza-Wittig reaction [80-84] and copper-catalyzed processes [85, 86], More recently, Domling and coworkers have developed a new approach for the synthesis of polycyclic compounds via Ugi MCR followed by a Pictet-Spengler reaction [87-89]. In 2011, apro-tocol for the rapid access to quinolin-2-(l//)-one scaffold was reported by a sequential 4-component Ugi-Knoevenagel condensation [90]. Hulme et al. have introduced a one-pot, two-step protocol for large-scale production of libraries of novel peptidomimetic-like fcM-pyrrolidinone tetrazoles via the Ugi-3CR-azide reaction of tethered keto ester methyl... 

In 1894, Emil Knoevenagel expanded on Hantzsch s work in two significant ways. First, he showed that this reaction could be promoted by any primary or secondary amine, not just the few primary amines demonstrated by Hantzsch. (In ICnoevenagel s hands, tertiary amines, such as pyridine, quinoline, diethylaniline or dimethylaniline were ineffective, although this was to be later revisited by Hann and Lapworth, vide infra). 

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