Knoevenagel condensation preparation

The cyanoacryhc esters are prepared via the Knoevenagel condensation reaction (5), in which the corresponding alkyl cyanoacetate reacts with formaldehyde in the presence of a basic catalyst to form a low molecular weight polymer. The polymer slurry is acidified and the water is removed. Subsequendy, the polymer is cracked and redistilled at a high temperature onto a suitable stabilizer combination to prevent premature repolymerization. Strong protonic or Lewis acids are normally used in combination with small amounts of a free-radical stabilizer. 

Many dihydropyridines that are of therapeutic interest are unsymmetrically substituted at C-3 and C-5. The synthesis of such compounds is possible from separately prepared Knoevenagel condensation products 6, as is outlined in the following scheme for nitrendipine 8, which is used in the medical treatment of high blood pressure." ... 

An early application of this reaction to the preparation of barbiturates starts by the condensation of the ketone, I21, with ethyl cyanoacetate by Knoevenagel condensation. Alkylation of the product (122) with ethyl bromide by means of sodium ethoxide affords 123. Condensation of this intermediate with guanidine in the presence of sodium ethoxide gives the diimino analog of a barbiturate (124). Hydrolysis affords vinbarbital (111). > ... 

A novel basic support and catalyst have been prepared by activation of aluminium phosphate with ammonia. Fine control of time and temperature allows to adjust the 0/N ratio of these oxynitride solids and thus to tune the acid-base properties. The aluminophosphate oxynitrides are active in Knoevenagel condensation, but a basicity range can not yet determined. Supporting Pt or Pt/Sn on AlPONs allows to prepare catalysts that are highly active and selective in dehydrogenation reactions. 

The domino process probably involves the chiral enamine intermediate 2-817 formed by reaction of ketone 2-813 with 2-815. With regard to the subsequent cy-doaddition step of 2-817 with the Knoevenagel condensation product 2-816, it is interesting to note that only a normal Diels-Alder process operates with the 1,3-bu-tadiene moiety in 2-817 and not a hetero-Diels-Alder reaction with the 1-oxa-l,3-butadiene moiety in 2-816. The formed spirocydic ketones 2-818/2-819 can be used in natural products synthesis and in medidnal chemistry [410]. They have also been used in the preparation of exotic amino adds these were used to modify the physical properties and biological activities of peptides, peptidomimetics, and proteins... 

The stereoselective total synthesis of both ( )-corynantheidine (61) (170,171) (alio stereoisomer) and ( )-dihydrocorynantheine (172) (normal stereoisomer) has been elaborated by Szdntay and co-workers. The key intermediate leading to both alkaloids was the alio cyanoacetic ester derivative 315, which was obtained from the previously prepared ketone 312 (173) by the Knoevenagel condensation accompanied by complete epimerization at C-20 and by subsequent stereoselective sodium borohydride reduction. ( )-Corynantheidine was prepared by modification of the cyanoacetate side chain esterification furnished diester 316, which underwent selective lithium aluminum hydride reduction. The resulting sodium enolate of the a-formyl ester was finally methylated to racemic corynantheidine (171). 

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. 

Recently, the first stable organic analog of a zeolite was prepared [58] which showed catalytic properties in the base-catalyzed Knoevenagel condensation. In... 

Scheme 33 Preparation of the substrate (220) for an intramolecular Knoevenagel condensation...

A rapid and low cost preparation of the tiE, 5Z )-alkadienyl system encountered in several insect pheromones has been developed. Knoevenagel condensation of (T )-2-alkenals with ethyl hydrogen malonate in DMSO, in the presence... 

In the last decade, the mesoporous molecular sieve MCM-41 has been developed (2S2) and applied as a catalyst to many acid-catalyzed reactions (2SS). However, until now, comparatively few investigations of mesoporous molecular sieves as base catalysts have been reported (169,211-214,234,235). For example, sodium- and cesium-exchanged mesoporous MCM-41 were shown to be mildly selective, water-stable, recyclable catalysts for the base-catalyzed Knoevenagel condensation, and mesoporous MCM-41 containing intraporous cesium oxide particles prepared by impregnation with aqueous cesium acetate and subsequent calcination was found to have strong-base activity for the Michael addition (211,213) and rearrangement of co-phenylalkanals to phenyl alkyl ketones (212). 

Pyrans 133 were obtained by spontaneous isomerization of dienones 132, smoothly prepared by the Knoevenagel condensation of 2,3-dime-thyl-2-butenal with 1,3-dicarbonyl compounds.175,176... 

Ethyl E7E -2,4-dienoutes.1 These diunsaturaled esters can be prepared by Knoevenagel condensation (piperidine catalyzed) of ethyl 2-phenylsulfinylacetate with aldehydes and thermolysis of the product in the presence of potassium carbonate (equation I). 

Several syntheses of 2//-pyrans are based on the preparation of the acyclic precursors (157b) in the hope that the dienone zZ 2//-pyran equilibrium will favor the heterocycle (157a). Often the product will contain both valence isomers. Such dienone precursors can be obtained by Knoevenagel condensation of 1,3-dicarbonyl compounds with a,(3-unsaturated aldehydes (Scheme 57). Simple 1,3-diketones yield the 2//-pyran directly (88IZV1815) and cyclohexan-l,3-diones afford fused pyrans (82S683, 84JHC913, 87JOC1972>. 

Numerous condensation polymers such as polyamides (75MI11103) containing the pyridine nucleus in the backbone have been prepared from the corresponding pyridine diesters or diacid chlorides. The Knoevenagel condensation (Scheme 32) has provided another way of incorporating the pyridine nucleus into a condensation framework. Poly(styrylpyridines) (116) have been found to exhibit exceptional flame resistance and are useful in reinforced composites (79USP4163740). 

Phenylcoumarins are conveniently prepared by the Knoevenagel condensation of salicylaldehyde with a benzyl cyanide, in the presence of base such as sodium hydroxide or piperidine, followed by acid hydrolysis of the resultant imine. A second convenient synthesis is via condensation of 2-methoxybenzaldehyde with benzyl cyanide and cyclization of the 2-methoxy-a-phenylcinnamic nitrile in pyridine (Scheme 12). 

Base catalysis is one of the less-well developed areas of heterogeneous catalysis. We have developed novel bases derived from amines via the one-step process outlined above. A range of supported amines have been prepared and evaluated in a series of reactions We have also investigated the nature of the amine groups attached to the surface in comparison with those formed by grafting onto pre-formed silica. While many workers have studied the use of basic catalysts for the Knoevenagel condensation of aldehydes, with three articles on the use of MCM derivatives[ 12], little has been done on the more demanding condensation of ketones. 

Elaboration of the side-chain of the salicylaldehyde (376) coupled with a Knoevenagel condensation enabled a number of naturally occurring coumarins such as xanthyletin (377) to be prepared (71CJC2297). The use of C-labelled malonic acid leading to coumarins labelled at C-3 enhances the potential of this route. 

Azobenzenes 5 were synthesized by coupling of the dialkyl aniline derivative 2 with 4-nitro- or 4-methyl-sulfonylbenzene diazonium salt (Figure 3). Vinylidine compound 6 was prepared by Knoevenagel condensation of the corresponding aldehydes with malononitrile (Figure 4). 

As a final example it should be mentioned that precondensed enones, prepared by standard Knoevenagel condensation of the aldehyde with the CH-acidic carbonyl component, when reacted with thioureas provided 1,3-thiazines 37, which are isomeric to thio-Biginelli compounds of the general formula 14 (see Figure 4.5). A published report describes the combinatorial synthesis of a library of 29 derivatives of thiazines 37 utilizing polymer-supported reagents and catalysts [168]. 

It consists of a Knoevenagel condensation [5] of an aldehyde with a 1,3-dicarbonyl compound in the presence of catalytic amounts of a weak base such as ethylene diammonium diacetate (EDDA) or piperidinium acetate (freshly prepared). In the reaction, a 1,3-oxabutadiene is formed as an intermediate, and this can undergo a hetero-Diels-Alder reaction [6] with either an enol ether or an alkene. 

Compound 85 was dehydrogenated at 300° over palladium black under reduced pressure to a pyridine derivative 96 which was independently synthesized by the following route. Anisaldehyde (86) was treated with iodine monochloride in acetic acid to give the 3-iodo derivative 87. The Ullmann reaction of 87 in the presence of copper bronze afforded biphenyldialdehyde (88). The Knoevenagel condensation with malonic acid yielded the unsaturated diacid 91. The methyl ester (92) was also prepared alternatively by a condensation of 3-iodoanisaldehyde with malonic acid to give the iodo-cinnamic acid (89), followed by the Ullmann reaction of its methyl ester (90). The cinnamic diester was catalytically hydrogenated and reduced with lithium aluminium hydride to the diol 94. Reaction with phosphoryl chloride afforded an amorphous dichloro derivative (95) which was condensed with 2,6-lutidine in liquid ammonia in the presence of potassium amide to yield pyridine the derivative 96 in 27% yield (53). 

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