Carbonyl compound nucleophilicity

The second fundamental reaction of carbonyl compounds, nucleophilic acyl substitution, is related to the nucleophilic addition reaction just discussed but occurs only with carboxylic acid derivatives rather than with aldehydes and ketones. When the carbonyl group of a carboxylic acid derivative reacts with a nucleophile, addition occurs in the usual way, but the initially formed tetra-... 

We have intentionally selected example reactions (Figs. 29-33) that would not usually be immediately obvious to a chemist. The examples chosen have all been concerned with rearrangements of various types, since their courses are frequently difficult to predict. It remains to emphasize that the reactivity functions contained in EROS perform perfectly well with other types of reaction. This is true, for example, with reactions that a chemist could derive directly from an analysis of the functional groups in a molecule. Thus, EROS predicts addition reactions to carbonyl compounds, nucleophilic substitutions, and condensation reactions, to name just a few examples. In all these reaction types, the possibility of assigning a quantitative estimate to the reactivity at the various sites via the reactivity functions is of particular merit. It... 

But the best El eliminations of all are with tertiary alcohols. The alcohols can be made using the methods of Chapter 9 nucleophilic attack by an organometallic on a carbonyl compound. Nucleophilic addition, followed by El elimination, is the best way of making this substituted cyclohexene, for example. Note that the the proton required in the first step is recovered in the last—the reaction requires only catalytic amounts of acid. 

Baylis-Hillman reaction a,p-Unsaturated carbonyl compounds Nucleophilic 243-245... 

Evidence, chiefly from kinetics and experiments with isotopically labeled compounds, indicates that even this seemingly different reaction follows the familiar pattern for carbonyl compounds nucleophilic addition. Two successive additions... 

Carbonyl compound Nucleophile Solvent Time(h) Temperature ( C) Product Yield (%)... 

The mechanism of the Mannich reaction has been extensively investigated. The reaction can proceed under both acidic and basic conditions, but acidic conditions are more common. Under acidic conditions the first step is the reaction of the amine component with the protonated non-enolizable carbonyl compound to give a hemiaminal, which after proton transfer loses a molecule of water to give the electrophilic iminium ion.°° This iminium ion then reacts with the enolized carbonyl compound (nucleophile) at its a-carbon in an aldol-type reaction to give rise to the Mannich base. 

The position of the equilibrium depends on the structure of the carbonyl compound. Nucleophilic addition is favoured by small alkyl groups attached to the carbonyl group and also by electron-withdrawing groups (e.g. CC13), which increase the 8+ character of the carbonyl carbon atom (see Section 8.3.1). 

In the presence of a base, hydroxylamine-G-sulfonic acid or chloramine aminate carbonyl compounds nucleophilically (Schmitz 1961), e.g. ... 

III. FROM CARBONYL COMPOUNDS NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP... 

Relationships between reactivities of carbonyl compound, nucleophile, and catalyst... 

Ruppert reagent (CFsSiMes) Carbonyl compounds (nucleophilic) Aromatics Safe and easy to handle Silicon-containing waste generated Expensive... 

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