Aldol condensation piperidine aldehyde

Another general method for the preparation of 19,19,19- and 20,20,20-trifluor-oretinals involves the aldol condensation of trifluoroacetone with an ethylenic aldehyde. When performed in the presence of acetic acid and piperidine, it affords an a, S-unsaturated ketone. Applied to cyclocitral and its homologues, the method leads to polyenic trifluoromethyl ketones. From these ketones, the various tri-fluorinated retinoids are prepared by known methods (Figure 4.24). ... 

The medicinal chemistry of Alzheimers is complicated by the fact that the etiology of this disease is still far from clear. Evidence points to an association with decreased levels of acetyl choline in the brain. Many of the drugs that have been introduced to date for treating this disease thus comprise agents intended to raise the deficient levels of that neurotransmitter by inhibiting the loss of existing acetylcholine due to the action of cholinesterase. A compound based on an indene that, perhaps surprisingly, inhibits that enzyme has been proposed for the treatment of Alzheimer s. Aldol condensation of piperidine aldehyde (4-2) with the indanone (4-1) from cyclization of 3,4-dimethoxycinnamic acid leads to the olefin (4-3). Catalytic reduction removes the double bond to afford donepezil (4-4) [3]. 

Preparation by reaction of ethyl acetoac-etate with 2-isobutyl-6-methyl-2-heptenal in the presence of pyridine and piperidine as catalysts in refluxing benzene (29%). The 2-isobutyl-6-methyl-2-heptenal was obtained by self-condensation of iso-capro-aldehyde in the presence of 15% potassium hydroxide solution (Aldol condensation) [2958-2960]. 

Aldol reactions, usually followed by dehydration, of /3-dicarbonyl compounds with the aldehyde forms of substituted nonnitrogenous monosaccharides are also known. 2,3-0-Isopropylidene-D-glyceraldehyde condenses with ethyl acetoacetate in the presence of piperidine, giving the 1,3-dideoxy-3-(ethoxycarbonyl)-5,C-0-isopropyIidenehexulose (54), presumably as a mixture of diastereoisomers, and 1,3,4-trideoxy-3-(ethoxy-carbonyl)-5,6-0-isopropylidene-D-gfi /cero-hex-3-enulose (55). Reaction of... 

Aldol-type condensation of an aromatic aldehyde with activated methylarene or phenylacetic acid is a useful reaction for preparing stilbene derivatives. Starting from para-substituted toluenes or para-substituted aromatic aldehydes, one can obtain 4,4 -disubstituted stilbenes. This reaction is relatively simple but has low yield. As an example, condensation of 2,4-dinitrotoluene and 4-nitrophenylacetic acid with aromatic aldehyde was studied [26]. The reaction involves carbanion addition to the carbonyl group. The carbanion is formed by the extraction of proton from the active methylene group of 2,4-dinitrotoluene by the base (usually, piperidine). The carbanion then adds to carbon atoms of the carbonyl group of the aldehyde. The reaction will therefore be facilitated by the ease of both the formation of the... 

Aldol-type condensations between but-2-enolides and carbonyl compounds constitute probably the most flexible routes to 4-ylidene-butenolides and 4-ylidenetetronic acids. One of the first applications of this general approach was in the preparation of (130) from but-2-enolide (129 a) employing aqueous sodium hydrogen carbonate as base 114). Bohlmann and Zdero 34) later described a synthesis of the naturally occurring thiophene (131) involving condensation between butenolide (129 b) and 5-methylthiophene-2-aldehyde in the presence of piperidine acetate in glacial acetic acid at 80°. 

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