Acetophenone Knoevenagel reaction

The rate of the Knoevenagel reaction of acetophenone 30 with ethyl cyanoacetate 31 (Scheme 4.16) was observed to be considerably slower and it was therefore found to be more suitable for rate studies [19]. 

Scheme 4.16 Knoevenagel reaction of acetophenone with ethyl cyanoacetate.

An improved version of the Knoevenagel reaction between acetophenones and aldehydes allows direct access to trarcr-2,3-disubstituted chroman-4-ones, examples of which show high anti-estrogenic activity <00T1811>. Reduction of flavanones by NaBUi leads to the 2,4-cis-flavan-4-ols from which 4-methoxyflavans can readily be obtained detailed H and 13C NMR data are provided <00T6047>. 

Isatins fail to yield Knoevenagel condensation products with malonic acid419. However, malonic acid can be condensed with isatin in a mixture of ethanol and pyridine, in which the initial condensation product suffers decarboxylation, furnishing an acetic acid derivative. This can be converted to the acid chloride and submitted to a Friedel-Crafts acylation reaction, yielding acetophenone derivatives420. Alternatively the oxoindolinylidene acetic acid derivative can be treated with an arene in the presence of AICI3 to yield. sy />o[indoline-3,3 -indan]-2,l-dione derivatives. ... 

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... 

Another frequently used reaction to estimate the number and strength of basic sites in zeolites is the Knoevenagel condensation. As an example, the Knoevenagel condensation of acetophenone and malononitrile is shown in Scheme 15. The reactions were studied, e.g., by Corma et al. [236-238] and Rodriguez et al. [239-241]. In this reaction, the basic sites in the zeolite abstract a proton from the methylenic compound, e.g., a nitrile or ester. The... 

The use of supported organocatalysts in flow chemistry is not new. A pioneering work using an organic base catalyst was reported by Venturello. Knoevenagel condensations of aromatic aldehydes, cyclohexanone, and acetophenone with acetoa-cetate, cyanoacetate, or malonate were catalyzed by aminopropyl-functionalized silica gel (56), which was packed in a gravity-fed column, under continuous-flow conditions (Scheme 7.40) [149]. A flowcell microreactor, whose wall surfaces were coated with aminopropylsilica, was utilized in Knoevenagel and Michael reactions [150]. 

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