Reactivity of aldehydes and ketones

The reactivity of aldehydes and ketones toward cyanide may be influenced by the steric and/or electronic properties of the carbonyl substituents, X. Examine spacefilling models of formaldehyde (X=H), acetone (X=Me), and benzophenone (X=Ph). Which compound offers the least steric hindrance to nucleophilic attack The most ... 

Now this is exactly the same situation we encountered when we compared the reactivity of aldehydes and ketones with that of carboxylic acid derivatives (see Section 7.8). The net result here is acylation of the nucleophile, and in the case of acylation of enolate anions, the reaction is termed a Claisen reaction. It is important not to consider aldol and Claisen reactions separately, but to appreciate that the initial addition is the same, and differences in products merely result from the absence or presence... 

Steric factors also play an important role in the reactivity of aldehydes and ketones. We may look at the relative ease with which the attacking nucleophile can approach the carbonyl carbon or consider how steric factors influence the stability of the transition state leading to the final product. 

More recently, the use of high pressure with tetra-n-butylammonium fluoride as catalyst allowed these reactions to be accomplished with cyclic ketones. Thus, the Henry reaction of nitroalkanes with 3- and 4-methylcyclohexanones in THF at 30 C and 9 kbar (1 bar = 100 kPa) afforded fair to high yields (60-90% after 4 d) of the corresponding nitro alcohols, while with 2-methyIcyclohexanones it was possible to obtain addition products, although in moderate yields. These facts explain the modest utility of the Henry reaction as a chain-lengthening reaction when the carbonyl component is a ketone, but also show the difference in reactivity of aldehyde and ketone C==0 groups with respect to nitromethane, primary and secondary nitroalkanes in the presence of a base as catalyst. Such a difference in reactivity can be considered as the most evident chemoselectivity of this reaction. 

Difference in reactivity of aldehydes and ketones was used for selective protection of aldehydes in the presence of a ketone functional group. Chemoselectivity is demonstrated by two competitive reactions. When a 1 1 mixture of p-hydroxy- or p-nitrobenzaldehyde and p-hydroxy- or p-nitroacetophenone was allowed to react with 1.0 equiv. of semicarbazide hydrochloride for 45 min, the aldehydes were transformed quantitatively to their corresponding semicarbazones 59, whereas the ketones remain unreacted (Scheme 3.14). 

The different reactivities of aldehydes and ketones with hydroxylamine hydrochloride were used as a method for protecting aldehydes by oximation in the presence of a ketone functional group. The competitive reactions with 1 1 mixtures of o-nitro- or p-nitrobenzaldehyde and o-nitro- or p-nitroacetophenone when milled with 1 equiv. of NH20H flCl for 60 min at 25°C afforded only the transformation of aldehydes to their corresponding oximes, whereas the ketones did not react. In a similar manner the difference in temperatures needed for the conversion of ketones into the 2,4-dinitrophenyIhydrazones was used for chemoselective reaction of aldehydes. As an example, milling of 1 1 mixture of p-nitrobenzaldehyde and p-nitroace-tophenone with 2,4-dinitrophenylhydrazine and water at 70°C for 50 min produced quantitative transformation of aldehyde to its 2,4-dinitrophenylhydrazone, whereas the ketone remained unaffected. 

The diflferent reactivity of aldehydes and ketones toward condensation with amines is also a differentiating element when using enals or enones as Michael donors under iminium activation. As in the enamine activation case, working with a,p-unsaturated aldehydes usually leads to faster reactions or better conversions but the same reaction with enones in many cases turns out to be a very slow or even non-existent reaction. Stereochemical control is also more problematic when a,p-unsaturated ketones are employed because the presence... 

This chapter will explore the reactivity of aldehydes and ketones. 

The reactivity of carboxylic add derivatives is similar to the reactivity of aldehydes and ketones in a number of ways. In both cases, the carbonyl group is electrophiUc and subject to attack by a nucleophile. In both cases, the same rules and principles govern the proton transfers that accompany the reactions, as we will soon see. Nevertheless, there is one critical difference between carboxyhc acid derivatives and aldehydes/ketones. Specifically, carboxylic acid derivatives possess a heteroatom that can function as a leaving group, while aldehydes and ketones do not. 

In the preceding chapter, we saw that the chemistry of the carbonyl group turns upon its polarity. In this chapter, we examine the differences in stability and reactivity of aldehydes and ketones. Many of the reactions we discuss occur by addition of a nucleophile to the carbonyl carbon and the addition of an electrophile to the carbonyl oxygen. Sometimes these reactions produce a stable, tetrahedral adduct, as we see in the compound shown at the left. In other cases, the tetrahedral adduct undergoes further reaction. Nucleophilic addition to carbonyl groups is a major new class of reaction mechanism. 

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