Carbonyl-based groups

The term Knoevenagel Condensation was originally applied to the base-catalysed condensation of the carbonyl ( CO) group of aldehydes and ketones with the reactive methylene group of malonic acid, with loss of w ater ... 

Base-catalyzed transformations can be carried out elsewhere on a complex molecule in the presence of such protected -dicarbonyl magnesium chelate. For example, the chelated magnesium enolate of a /3-ketoester such as 71 prevents the carbonyl keto group becoming an acceptor in aldol condensations. However, in the presence of excess of magnesium methanolate, exchange of the acetyl methyl protons can occur via a carbanion 72 stabilized by delocalization into the adjacent chelate system (equation 99). 

The hydrogens on the methylene unit located between the two carbonyl functional groups are acidic due to the electron withdrawing effects of the carbonyl groups. Either or both of these hydrogens can be removed by reaction with strong bases. 

In the first case [1] Y can be either a hydroxy, alkoxy or nitro group. The first two groups are important but variable constituents in coals and the last is probably minor or non-existent. The second active class of species are the alkyl-pyridines [2]. The final case [3] includes substituents on the benzyl carbon where X can be an ether or carbonyl functional group. The general mechanism of this reaction is most probably the base catalyzed iodination of the benzyl carbon with subsequent displacement of the iodide by the pyridine to form the pyridinium salt. In all three modes of activation, the single aromatic ring can be replaced with polycyclic rings. 

An alternative method, which uses the base-labile 9-fluorenylmethoxy-carbonyl (Fmoc) group to protect the a-amino group in combination with... 

Extending beyond alcohols and ethers, conjugate acids of carbonyl-based functional groups are known. Specifically referring to carboxylic acids and esters, the corresponding conjugate acids, illustrated in Scheme 3.7, have pKa values around 6. Furthermore, protonated aldehydes and ketones, illustrated in Scheme 3.8, have p/Ca values ranging from 7 to 9. 

Scheme 3.9 Carbonyl-based functional groups delocalize charges through resonance.

Scheme 3.10 Protonated carbonyl-based functional groups delocalize their positive charges.

Scheme 3.11 Protonated carbonyl-based functional groups are susceptible to reaction with...

In our present discussions, 1,2- and 1,4-additions to carbonyl systems were introduced. However, these reactions were not presented in the context of specific carbonyl-based functional groups. Expanding upon this concept, the three types of functional groups generally used in addition reactions to carbonyls are aldehydes, ketones, and esters. 

Figure 7.3 Unlike most carbonyl-based functional groups, nonconjugated esters can react with nucleophiles and retain the carbonyl unit.

Addition-elimination reactions are not exclusive to esters. In fact, these reactions can occur with any carbonyl-based system where the leaving group is a weaker nucleophile... 

We have used nitro groups very extensively so far and that is only right and proper as they are the best at stabilizing the anionic intermediate. Others that work include carbonyl, cyanide, and sulfur-based groups such as sulfoxides and sulfones. Here is a direct comparison for the displacement of bromide ion by the secondary amine piperidine. First the reaction with a carbonyl group. 

The relative reactivity of the alcohol and amine in the example just given could be overturned by conducting a reaction under thermodynamic control. In kinetically controlled reactions, the idea that you can conduct chemoselective reactions on the more reactive of a pair of functional groups— carbonyl-based ones, for example—is straightforward. But what if you want to react the less reactive of the pair There are two commonly used solutions. The first is illustrated by a compound needed by chemists at Cambridge to study an epoxidation reaction. They were able to make the following diol, but wanted to acetylate only the more hindered secondary hydroxyl group. 

Alkylation of the lower rim substitution with carbonyl-containing groups (101) has produced probably the most widely studied of the calixarene-based ionophores. These derivatives have been studied predominantly as ionophores for hard metal cations, and can form complexes of comparable stability to those of the cryptands in some cases. Such calixarenes have found applications as ionophores in ion selective electrodes. ... 

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