19.0: Why This Chapter? Much of organic chemistry is the chemistry of carbonyl compounds. Aldehydes and ketones, in particular, are intermediates in the synthesis of many pharmaceutical agents, in almost all biological pathways, and in numerous industrial processes, so an understanding of their properties and reactions is essential. In this chapter, we’ll look at some of their most important reactions. 19.1: Naming Aldehydes and Ketones Aldehydes are named by replacing the terminal -e of the corresponding alkane name with -al. The parent chain must contain the –CHO group, and the –CHO carbon is numbered as carbon 1. 19.2: Preparing Aldehydes and Ketones Perhaps the best method of aldehyde synthesis is by oxidation of a primary alcohol. The reaction is usually carried out using the Dess–Martin periodinane reagent in dichloromethane solvent at room temperature. 19.3: Oxidation of Aldehydes and Ketones Aldehydes are easily oxidized to yield carboxylic acids, but ketones are generally inert toward oxidation. The difference is a consequence of structure: aldehydes have a –CHO proton that can be abstracted during oxidation, but ketones do not. 19.4: Nucleophilic Addition Reactions of Aldehydes and Ketones The most general reaction of aldehydes and ketones is the nucleophilic addition reaction. In general, a nucleophile, :Nu–, approaches the carbonyl group from an angle of about 105° opposite the carbonyl oxygen and forms a bond to the electrophilic C–O carbon atom. 19.5: Nucleophilic Addition of Water- Hydration Aldehydes and ketones react with water to yield 1,1-diols, or geminal (gem) diols. The hydration reaction is reversible, and a gem diol can eliminate water to regenerate an aldehyde or ketone. 19.6: Nucleophilic Addition of HCN - Cyanohydrin Formation The nucleophilic addition of hydrogen cyanide (HCN) to aldehydes and ketones leads to the formation of cyanohydrins. The reaction mechanism involves the nucleophilic attack of the cyanide ion on the carbonyl carbon, followed by protonation. Cyanohydrins are valuable intermediates in organic synthesis and are important in various chemical applications. 19.7: Nucleophilic Addition of Hydride and Grignard Reagents- Alcohol Formation This section explains the nucleophilic addition reactions of aldehydes and ketones using hydride and Grignard reagents to form alcohols. Hydride reagents like sodium borohydride and lithium aluminum hydride reduce carbonyl compounds, while Grignard reagents, being strong nucleophiles, add to carbonyls to yield alcohols after hydrolysis. The text emphasizes the mechanisms, products, and implications of these reactions in organic synthesis. 19.8: Nucleophilic Addition of Amines- Imine and Enamine Formation Primary amines, RNH₂, add to aldehydes and ketones to yield imines, R₂C═NR . Secondary amines, R2NH, add similarly to yield enamines, R₂N–CR═CR₂ (ene + amine = unsaturated amine). 19.9: Nucleophilic Addition of Hydrazine - The Wolff-Kishner Reaction A useful variant of the imine-forming reaction just discussed involves the treatment of an aldehyde or ketone with hydrazine, H2N–NH2, in the presence of KOH. Called the Wolff–Kishner reaction, the process is a useful and general method for converting an aldehyde or ketone into an alkane. 19.10: Nucleophilic Addition of Alcohols - Acetal Formation Aldehydes and ketones react reversibly with 2 equivalents of an alcohol in the presence of an acid catalyst to yield acetals, R₂C(OR′)₂, which are often called ketals if derived from a ketone. Cyclohexanone, for instance, reacts with methanol in the presence of HCl to give the corresponding dimethyl acetal. 19.11: Nucleophilic Addition of Phosphorus Ylides- The Wittig Reaction Aldehydes and ketones are converted into alkenes by means of a nucleophilic addition called the Wittig reaction, after the German chemist Georg Wittig who won the 1979 Nobel Prize in Chemistry. The reaction has no direct biological counterpart but is important both because of its wide use in drug manufacture and because of its mechanistic similarity to reactions of the coenzyme thiamin diphosphate. 19.12: Biological Reductions The tetrahedral intermediate produced by addition of a nucleophile to a carboxylic acid derivative can eliminate a leaving group, leading to a net nucleophilic acyl substitution reaction. The tetrahedral intermediate produced by addition of a nucleophile to an aldehyde or ketone, however, has only alkyl or hydrogen substituents and thus can’t usually expel a leaving group. One exception to this rule is the Cannizzaro reaction. 19.13: Conjugate Nucleophilic Addition to α,β‑Unsaturated Aldehydes and Ketones This section covers the conjugate nucleophilic addition of nucleophiles to unsaturated aldehydes and ketones. It explains how these reactions differ from standard nucleophilic additions due to the presence of α,β-unsaturated carbonyl compounds. The mechanism involves the nucleophile attacking the β-carbon, leading to the formation of more complex products. This process is essential in organic synthesis and has significant applications in creating diverse chemical compounds. 19.14: Spectroscopy of Aldehydes and Ketones Aldehydes and ketones show a strong C═O bond absorption in the IR region from 1660 to 1770 cm⁻¹, as the spectra of benzaldehyde and cyclohexanone demonstrate. In addition, aldehydes show two characteristic C–H absorptions between 2700–2760 and 2800–2860 cm⁻¹. These absorbances are important for distinguishing between aldehydes and ketones. Aldehyde protons (RCHO) absorb near 10 δ in the 1H NMR spectrum and are very distinctive because no other absorptions occur in this region. 19.15: Chemistry Matters—Enantioselective Synthesis Whenever a chiral product is formed by reaction between achiral reagents, the product is racemic; that is, both enantiomers of the product are formed in equal amounts. Unfortunately, it’s usually the case that only one enantiomer of a given drug or other important substance has the desired biological properties. Thus, much work is currently being done on developing enantioselective methods of synthesis, which yield only one of the two possible enantiomers 19.16: Key Terms 19.17: Summary Aldehydes and ketones are among the most important of all functional groups, both in the chemical industry and in biological pathways. In this chapter, we’ve looked at some of their typical reactions. Aldehydes are normally prepared in the laboratory by oxidation of primary alcohols or by partial reduction of esters. Ketones are similarly prepared by oxidation of secondary alcohols. 19.18: Summary of Reactions This section summarizes the key reactions involving aldehydes and ketones, highlighting their nucleophilic addition reactions. It covers the formation of alcohols from hydride and Grignard reagents, as well as the reaction of carbonyl compounds with other nucleophiles. The importance of these reactions in organic synthesis is emphasized, detailing the mechanisms and various products formed.