This chapter concentrates on the chemistry of aldehydes (RCHO) and ketones (RCOR) and how they react in nucleophilic addition reactions. An aldehyde contains a C=O group bonded to at least one hydrogen atom, whereas a ketone has a carbonyl group bonded to two alkyl or aryl groups. The chapter illustrates general mechanisms for a nucleophilic addition reaction, an α-substitution reaction, and a carbonyl–carbonyl condensation reaction and mechanisms for nucleophilic addition reactions of aldehydes and ketones using reagents. It discusses keto–enol tautomerism and the factors that influence the stability of keto and enol forms. The structure of a product derived from a nucleophilic addition, an α-substitution, or a carbonyl–carbonyl condensation reaction of an aldehyde or ketone are also covered.
Chapter
Aldehydes and ketones
Nucleophilic addition and α-substitution reactions
Chapter
Enolate alkylations with alkyl halides
This chapter addresses enolate alkylations with alkyl halides. Simple enolates react irreversibly with soft (polarized) electrophiles such as methyl iodide. A new carbon–carbon bond is formed in an S
N
2, which is of considerable synthetic importance. The chapter then looks at enolates derived from simple ketones, simple esters, and β dicarbonyl compounds. If cyclohexanone is treated with ethanolic sodium ethoxide in the presence of methyl iodide, most of the latter reacts with ethoxide ion. However, if the considerably more hindered and slightly more basic t-butoxide is used as base, little reaction of it with the methyl iodide occurs. The difficulty arises from the fact that substantial concentrations of bases derived from alcohols are necessary to obtain even small concentrations of enolates from simple ketones.
Chapter
Reactions of hydroxyl groups Part II: cyclic acetals
This chapter deals with the reactions of carbohydrate hydroxyl groups with other aldehydes and ketones to form cyclic acetals, which are utilized as a means of protecting particular sugar hydroxyl groups. It explains why the reaction of carbohydrates with acetone and acid produces cyclic 5-ring acetonides, whereas benzaldehyde and acid produce 6-ring benzylidenes. It also looks at the reaction of glucose with acetone and acid. This produces the pyranose diacetonide with only the 6-hydroxyl group free. The chapter then discusses the reaction of glucose with acetone and acid. This produces furanose diacetonide with 3-hydroxyl group free. It explains the protection of carbohydrates as butane diacetals. This results in selective protection of vicinal diequatorial diol groups.
Chapter
Organometallic compounds
This chapter covers the most useful organometallic compounds R-M with M = Li, Mg, or Cd, including Zn compounds and lithium cuprates. It illustrates the main features of R-Mg-Hal as reagents in synthetic work and reactions that produce Mg derivatives from which the products are liberated by a treatment with dilute acid. It also discusses the reactions with esters that result in ketones or aldehydes, which cannot be isolated under standard conditions. The chapter refers to the instability of intermediates, which is are not readily predicted by organic theory and stems from the decrease of free energy associated with their decompositions. It highlights the formation of the tertiary alcohol in high yield by R-Li, which provides a sharp contrast and exemplifies the modern trends towards the use of reagents.
Chapter
Preparation of bifunctional compounds
This chapter describes methods used to prepare bifunctional compounds, which are usually specific to the particular combination of functional groups. It explains the retro-synthetic analysis, which is an approach to the synthesis of 1,2-bifunctional compounds that considers as a possible precursor the alkene that would result from eliminating the two functional groups. The chapter also considers an alternative approach that involves imagining cleaving the bond which links the two functionalized carbon atoms. The chapter emphasizes that working backwards is a logical way to tackle the synthesis of a given target molecule as it leads to a selection of appropriate methods for bringing about forward transformation. It details the preparation of 1,2-diols by preparing hydroxylation of alkenes, reductive dimerization of ketones, or nucleophilic addition to α-hydroxycarbonyl compounds.
Chapter
Reactions of hydroxy- and aminocarbonyl compounds
This chapter examines hydroxyaldehydes and ketones that react intramolecularly to form cyclic hemiacetals. It highlights the production of five- or six-membered rings, wherein the cyclizationcyclisation becomes so facile that it occurs even under neutral conditions. It also talks about the equilibrium betweenSince the hydroxycarbonyl compound and the cyclic hemiacetalhemiciacetal are in a solution, compounds which do not formally display a carbonyl group that may undergo the reactions of a carbonyl compound. The chapter cites glucose as an example of a hydroxyaldehyde that exists mainly in the form of its hemiacetal, both in the solid state and in solution. It refers to the open chain aldehyde and the six-membered cyclic hemiacetal that are in equilibrium in solution, causing glucose to react as an aldehyde.
Chapter
Aldehydes and Ketones
This chapter describes aldehydes and ketones. Aldehydes have one alkyl group and one hydrogen atom attached to the carbonyl carbon. Ketones have two alkyl groups and resist oxidation. Both aldehydes and ketones contain the carbonyl group which has a carbon atom doubly bonded to an oxygen atom. Fehling's solution and Tollens' reagent can also help determine the differences between aldehydes and ketones. Oxidation can also help the reduction of aldehydes and ketones to primary and secondary alcohols respectively. The chapter also explains nucleophilic addition, condensation reactions, and alpha carbon reaction of aldehydes and ketones.
Chapter
Oxidation of carbon-carbon double and triple bonds
This chapter examines the oxidation of carbon–carbon double and triple bonds. The oxidation of carbon–carbon π-bonds can yield several useful functional groups. Many oxidising agents have been developed for this purpose. In fact, one of the main advantages of oxidising alkenes is that the product distribution can be controlled, and a particular functional group formed, simply by the choice of oxidant. The chapter begins by looking at the oxidation of alkenes to form epoxides. Epoxides are the cyclic ethers that may be formed from the reaction of an alkene with an oxidising agent. They are electrophiles and they react with nucleophiles such as water. The chapter then considers the addition to alkenes via epi-ions; the oxidation of alkenes to syn diols; the formation of ketones from alkenes and the Wacker process; and the oxidation of alkynes to 1,2-diketones.
Chapter
Allylboranes and boron enolates
This chapter considers allylboranes in organic synthesis. Focusing on the stability of allylboranes, the chapter displays how allyldialkylboranes can be used in further reactions if either they are prepared and used directly at low temperature, or the predominant isomer at equilibrium is the required isomer. The chapter also discusses the reaction of allylboranes with carbonyl compounds. It examines how triallylboranes react with aldehydes and ketones to give, on hydrolysis, homoallylic alcohols. The chapter then investigates the synthesis of homochiral homoallylic alcohols containing one chiral centre, and the synthesis of homoallylic alcohols containing two chiral centres. It ends with a discussion of boron enolates in organic synthesis.
Chapter
The addition of nucleophilic reagents to aldehydes and ketones
This chapter discusses the addition of nucleophilic reagents to aldehydes and ketones. In the series formaldehyde–acetaldehyde–acetone, reactivity to nucleophiles decreases in that order. The electronic factor here is deactivating, but slight, because the additional Me groups are not attached directly to the carbonyl carbon. They are largely insulated from it by saturated carbon atoms. The chapter then considers high degrees of hydration at equilibrium, which generally result when the carbonyl group has strong electron-withdrawing substituents attached, and in extreme cases it is the hydrate which is the familiar form of the carbonyl compound. It also looks at hemiacetal and hemiketal formation; cyanohydrin formation; bisulfate addition; the Meerwein–Ponndorf–Verley reaction; the Cannizzaro reaction; and reaction with Grignard reagents.
Chapter
Reactions of amino compounds with aldehydes and ketones
This chapter investigates the reactions of amino compounds with aldehydes and ketones. Amino nucleophiles ~NH2 react reversibly with aldehydes and ketones. The reversible reaction of ~NH2 with an aldehyde or ketone is very similar to that of water, involving as it does nucleophilic addition followed by dehydration. Secondary amines R2NH are intrinsically just as nucleophilic as primary amines RNH2. They react with aldehydes and ketones similarly, except that the final stage is blocked because there is no proton to discard, so iminium ions are generated. The chapter then looks at classical aldehyde and ketone derivatization, as well as reactions of ammonia and primary amines with aldehydes and ketones. It also considers enamines, the Wolf–Kishner reaction, and transamination.
Chapter
Review of spectroscopic methods
This chapter presents a review of spectroscopic methods. It begins by looks at spectroscopy and carbonyl chemistry. Carbonyl compounds can be divided into two main groups: aldehydes and ketones, and acids and their derivatives. Which spectroscopic methods most reliably distinguish these two groups? Which help separate aldehydes from ketones? Which allows us to distinguish the various acid derivatives? The most consistently reliable method for doing this is 13C nuclear magnetic resonance (NMR). It does not matter much whether the compounds are cyclic or unsaturated or have aromatic substituents, they all give carbonyl 13C shifts in about the same regions. The chapter then looks at NMR spectra of alkynes and small rings.
Chapter
Nucleophilic addition to the carbonyl group
This chapter details the simplest of all organic reactions: the addition of a nucleophile to a carbonyl group. Nucleophilic additions to carbonyl groups generally consist of two mechanistic steps: nucleophilic attack on the carbonyl group and protonation of the anion that results. Why does cyanide, in common with many other nucleophiles, attack the carbonyl group? And why does it attack the carbon atom of the carbonyl group? To answer these questions, the chapter looks in detail at the structure of carbonyl compounds in general and the orbitals of the C=O group in particular. The chapter then considers the attack of cyanide on aldehydes and ketones; the acid and base catalysis of hemiacetal and hydrate formation; and bisulfite addition compounds.
Chapter
Silyl protecting groups
This chapter evaluates silyl protecting groups. To categorise silicon protecting groups as either acid or base-labile is impractical because both types of cleavage are possible and find routine use. Organosilicon chemistry is characterised by a high affinity for oxygen, which has led to the widespread use of silyl ethers for the protection of alcohols, and higher affinity for fluorine, which provides a very selective deprotection pathway. The chapter then looks at alcohols, diols, aldehydes and ketones, and amines. Deprotection of silyl protecting groups with F-ion is normally highly selective but the basic properties of the hydrated ion in solution can interfere with functionality not containing silicon and can lead to unexpected reactions.
Chapter
Reactions of diols
This chapter describes 1,2-diols that undergo acid-catalysed rearrangement to afford ketones, which is a general reaction that involves the generation of a carbocation intermediate. It refers to the driving force of the general reaction of 1,2-diols that is provided by the resonance stabilization of the resulting carbocation. It also explains how diols react with aldehydes and ketones under anhydrous conditions to give acetals and ketals, which is a reaction that is acid-catalysed and proceeds most readily when the heterocyclic ring formed is five- or six-membered. The chapter discusses a transformation that can be used to protect aldehydes, ketones, and diols, while other reactions that involve base treatment or reduction are carried out elsewhere in the molecule. It demonstrates a reaction wherein diols are cyclized to form cyclic ethers; this can be carried out under acidic conditions.
Chapter
Reactions of nucleophiles with carbonyl compounds
This chapter assesses reactions of nucleophiles with carbonyl compounds. In the context of organic synthesis, reactions of carbonyl compounds are probably the most useful of all; they are also amongst the most varied. This is because carbonyl is both the functional group of simple aldehydes and ketones, and also a principal component of a range of the more complex functional groups of carboxylic acid derivatives. Functional groups which include a carbonyl are very widespread in the molecules of nature. An understanding, therefore, of how the carbonyl group reacts is essential for the study of biological chemistry as well as organic synthesis. These reactions are invariably with nucleophiles at the carbon atom, as expected of a functional group with the polarity represented by the partial structure, although complexation of an electrophile by a lone pair on the oxygen sometimes leads to electrophile catalysis.
Chapter
Enamines, enol ethers, and enolates
This chapter deals with enamines, enol ethers, and enolates. Enamines are nucleophilic reagents that undergo alkylation, acylation, and conjugation addition reactions. The chapter elaborates how enamines afford an indirect route for preparing substituted carbonyl compounds, noting that they are prepared from aldehydes and ketones and their salts are hydrolysed by aqueous acid to regenerate the carbonyl group. It explains that for aldehydes and ketones, the enol tautomer is less stable than the keto form and only very little enol is present. The chapter highlights that the enol tautomer predominates for some carbonyl compounds due to extra stabilization afforded by intramolecular hydrogen bonding. It explains that the interconversion of the keto and enol forms is catalysed by acid or base.
Chapter
Reactions with nucleophiles
This chapter focuses on organic reactions with nucleophiles. Nucleophiles are 'electron-rich' and have either non-bonded pairs of electrons or π-bonds; they can be anions or neutral molecules. Nucleophiles can react with species which have either positive charge or low electron density. This is the basis of many reactions, which begin with the transfer of electron density from the more electron-rich atom (in the nucleophile) to the more electron-deficient atom (in the electrophile). The chapter then looks at nucleophilic substitution reactions of haloalkanes; substitution reactions of alcohols; polymerization of cyclic ethers; the carbocation intermediate; and the competition between nucleophilic substitution and elimination. It also considers the reactions of nucleophiles with aldehydes and ketones; the reactions of nucleophiles with esters, carboxylic acids, and derivatives; the comparison of acid derivatives with aldehydes and ketones; and the comparison of the reactivities of the different types of halocompound with nucleophiles.
Book
Michael Clugston, Malcolm Stewart, and Fabrice Birembaut
Making the transition to university chemistry aims to help students make the significant step from school to university, setting them up to be confident and successful in their chemistry studies. The book begins by looking at the basic atomic structure, bonding, and molecular shape. There is a chapter on moles. The text turns to the different states of matter after that. There are also chapters on thermochemistry, chemical equilibrium, and acid-base equilibrium. The middle of the book moves on to look at redox reactions, spontaneous change, entropy, and Gibbs energy. The periodic table is also examined, as are the halogens and transition metals. Hydrocarbons are considered. Towards the end, the text moves on to aldehydes and ketones, carboxylic acids and their derivatives, polymers, and instrumental analysis.
Chapter
Nucleophilic Addition to the Carbonyl Group in Aldehydes and Ketones
This chapter discusses the polarity of the carbonyl bond and the catalysis of nucleophilic addition to carbonyl groups by acids and bases. It considers in detail the reactions of a functional group, and looks at nucleophilic additions to the carbonyl group of aldehydes and ketones. The chapter argues that these reactions provide clear examples of several fundamental principles of organic reaction mechanisms, and they also include some of the most useful reactions for organic synthesis. The carbonyl (>C=O) group is a functional group found in aldehydes and ketones as well as carboxylic acids and their derivatives, and is one of the most important in organic and biological chemistry. The chapter ends by explicating the acetal and dithioacetal formation as well as the Wittig reaction. It also investigates the formation of imines and enamines.
