Ammonium acetate Knoevenagel reaction

The formation of ethyl isopropylidene cyanoacetate is an example of the Knoevenagel reaction (see Discussion before Section IV,123). With higher ketones a mixture of ammonium acetate and acetic acid is an effective catalyst the water formed is removed by azeotropic distillation with benzene. The essential step in the reaction with aqueous potassium cyanide is the addition of the cyanide ion to the p-end of the ap-double bond ... 

A wide variety of M W-assisted aldol [59, 60] and Knoevenagel condensation reactions have been accomplished using relatively benign reagents such as ammonium acetate [61], including the Gabriel synthesis of phthalides with potassium acetate [62],... 

A series of tetrasubstituted thiazole derivatives 28 has been prepared via a multi-component tandem protocol <07T10054>. Reaction of bis(aroylmethyl)sulfides 23 with aryl aldehydes and ammonium acetate in 1 2 1 ratio under solvent-free microwave irradiation affords 28 in good yields. This reaction presumably starts with Knoevenagel condensation of sulfide with 2 equiv. of aryl aldehydes to give 24. Michael addition with ammonia and concomitant cyclocondensation lead to 26. Base-catalyzed ring opening of 26 to 27 and ring... 

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... 

Reactions of chrotnene 168 (Scheme 32) with Knoevenagel adducts derived from aldehydes and ethyl cyanoacetate or malononitrile and ammonium acetate yielded, after condensation, libraries of general structure 169 and 170, respectively [69]. 

Once obtained, these substituted benzaldehydes could be converted into amphetamines by an interesting variant of the Knoevenagel reaction as described in Chapter 9. They could be reacted in a mixture of nitroethane and ammonium acetate to form the appropriately substituted... 

On the other hand the catalyst is of great importance primary, secondary or tertiary amines or their corresponding ammonium salts are usually used, but many other catalysts such as phase transfer catalysts, Lewis acids or potassium fluoride can also be applied. The most widely employed catalysts are pyridine, with or without added piperidine, and ammonium salts, such as ammonium or piperidinium acetate. Condensations that employ strong bases or preformed metal salts of the methylene component are not covered here since transformations under these conditions are not usually considered to be Knoevenagel reactions. 

Steroidal ketones have been used extensively in the Knoevenagel reaction. Thus, die transformation of 17-oxoandrostane derivatives (309), which are readily available by microbiological degradation of sitosterin, are employed for the synthesis of enantiomerically pure cardiotonic steroids such as bufa-dienolide and cardenolide (311). In toth syntheses the substitutent at C-17 is introduced by a Knoevenagel reaction of the 17-oxoandrostane derivative (309) with ethyl cyanoacetate in the presence of ammonium acetate to give the cyano ester (310), presumably as a mixture of the ( )- and (Z)-isomers, in 89% yield.5 5... 

Piperidoius. The Knoevenagel reaction of aryl or heterocyclic aldehydes with ethyl 4-nitrobutanoate in the presence of ammonium acetate has been used for the synthesis of 2-piperidones (equation I). 

A similar reaction was published by Song et al. in 2013 (Scheme 13.29) [47]. 2-Hydroxynaphthoquinone 75 was reacted with aromatic aldehydes 97 and ethyl 4,4,4-lrifluoro-3-oxobutanoate 98 catalyzed by a mixture of ammonium acetate and acetic acid (25mol% each). A Knoevenagel-Michael addition sequence was followed by hemiketal formation to give the desired product 99 in moderate to good yields. Dehydration of the product yielded the 4 f-pyran derivatives. 

In a related transformation, the same group described a three-component domino reaction of 2-hydroxy-l,4-naphthoquinone, acting as a P-dicarbonyl surrogate, aromatic aldehydes and 1-(2-oxo-2-phenylethyl)pyridinium bromides in the presence of ammonium acetate, in water under microwave irradiation, that affords naphtho[2,3-Z)]furan-4,9-diones 31 [22]. Mechanistically, this domino reaction probably follows the same Knoevenagel-Michael intramolecular S 2 pathway described for the preparation of compounds 28, with ammonium acetate acting in this case as the base, to give intermediates 33. These compounds, which can be considered as tautomers of a hydroquinone species, would be finally transformed into the observed quinones by air-promoted oxidation, yielding the final products 31 (Scheme 1.16). 

Like many other MCRs, the Hantzsch protocol usually commences with a condensation reaction that produces an imine from the amine and aldehyde. In this case, however, the Knoevenagel adduct undergoes addition by the nucleophilic p-keto ester, which generates the intermediary dihydropyranol. Ammonium acetate addition then finally initiates the expected cyclocondensation to give the aminal. Although the... 

Bhuiyan et al. (2012) reported that arylidene-malononitrile can be prepared by Knoevenagel condensation reaction of malononitrile with corresponding aromatic aldehydes in presence of ammonium acetate (NH OAc), using microwave irradiation under solvent-free condition. The reaction proceeds in a clean manner with shorter reaction time, mild reaction condition, ecofriendly and with excellent yields as compared to conventional methods. A variety of functional groups such as nitro, chloro, amino and ether survived under the reaction conditions. 

Butylation of phenylacetonitrile with aqueous NaOH, as shown in Scheme 25, proceeds faster by use of high DF (>0.5) anion exchange resins.The strongly alkaline conditions degrade the quaternary ammonium ions of the catalyst. Catalyst (64) (1% DVB) is active for alkylation of phenylacetonitrile and benzyl phenyl ketone, and for Williamson ether synthesis, and it is much more stable in base than AERs. AERs in OH form are catalysts for dichlorocyclopropane syntheses from alkenes, chloroform and solid sodium hydroxide, and for dehydration of amides to nitriles. AERs in the appropriate hydroxide, acetate, or cyanide form are catalysts for aldol condensations, Michael reactions, Knoevenagel condensations, cyanoethylations and cyanohydrin syntheses. " ... 

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