Acid-Catalyzed Halogenation of Aldehydes and Ketones

Part of the evidence that supports these mechanisms comes from studies of reaction kinetics. Both base-promoted and acid-catalyzed halogenations of ketones show initial rates that are independent of the halogen concentration. The mechanisms that we have written are in accord with this observation In both instances the slow step of the mechanism occurs before the intervention of the halogen. (The initial rates are also independent of the nature of the halogen see Review Problem 18.5.) 

Why do we say that the halogenation of ketones in a base is base promoted rather than 

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As m the acid catalyzed halogenation of aldehydes and ketones the reaction rate is mde pendent of the concentration of the halogen chlorination brommation and lodmation all occur at the same rate Formation of the enolate is rate determining and once formed the enolate ion reacts rapidly with the halogen... 

Halogenation of Aldehydes and Ketones 827 [ A MECHANISM FOR THE REACTION ] Acid-Catalyzed... 

Sulfur tetrafluoride [7783-60-0] SF, replaces halogen in haloalkanes, haloalkenes, and aryl chlorides, but is only effective (even at elevated temperatures) in the presence of a Lewis acid catalyst. The reagent is most often used in the replacement of carbonyl oxygen with fluorine (15,16). Aldehydes and ketones react readily, particularly if no alpha-hydrogen atoms are present (eg, benzal fluoride [455-31-2] from benzaldehyde), but acids, esters, acid chlorides, and anhydrides are very sluggish. However, these reactions can be catalyzed by Lewis acids (HP, BF, etc). 

Simple olefins do not usually add well to ketenes except to ketoketenes and halogenated ketenes. Mild Lewis acids as well as bases often increase the rate of the cycloaddition. The cycloaddition of ketenes to acetylenes yields cyclobutenones. The cycloaddition of ketenes to aldehydes and ketones yields oxetanones. The reaction can also be base-catalyzed if the reactant contains electron-poor carbonyl bonds. Optically active bases lead to chiral lactones (41-43). The dimerization of the ketene itself is the main competing reaction. This process precludes the parent compound ketene from many [2 + 2] cycloadditions. Intramolecular cycloaddition reactions of ketenes are known and have been reviewed (7). 

Aldehydes and ketones react with halogens at the a-position via the enol or enolate, depending on the solution pH (Figure 17.14). For the acid-catalyzed reaction, the acid is usually HBr or HOAc, and a typical reaction mechanism is shown in Figure 17.15. In acid, the enol reacts with bromine in base, the enolate is the reacting species. The enolate, as you might expect (remember that the phenolate anion is a better nucleophile than neutral phenol), is the better nucleophile. However, irrespective of pH, the rate of bromination is not dependent on the concentration of molecular bromine. The RDS is enolization, and subsequent reaction of the enol/enolate with bromine is fast. 

It is not the aldehyde or ketone itself that is halogenated, but the corresponding enol or enolate ion. The purpose of the catalyst is to provide a small amount of enol or enolate. The reaction is often done without addition of acid or base, but traces of acid or base are always present, and these are enough to catalyze formation of the enol or enolate. With acid catalysis the mechanism is... 

Organometallic compounds or carbanions undergo a number of reactions in which the carbanion or carbanion-like moiety of the organometallic compound acts as a nucleophilic displacing agent. Examples are the formation of hydrocarbons from alkyl halides, alkyl halides from halogens, and ketones from acid chlorides or esters. The latter two reactions are closely related to the base-catalyzed condensations and are perhaps additions as well as displacement reactions. Related addition reactions are the carbonation of organometallic compounds and the addition to ketones or aldehydes. 

Mechanism 22-6 Base-Promoted Halogenation 1054 Mechanism 22-7 Final Steps of the Haloform Reaction 1056 Mechanism 22-8 Acid-Catalyzed Alpha Halogenation 1058 22-6 Alpha Bromination of Acids The HVZ Reaction 1059 22-7 The Aldol Condensation of Ketones and Aldehydes 1060... 

Addition of an Enolate to Ketones and Aldehydes (a Condensation) 1046 Substitution of an Enolate on an Ester (a Condensation) 1046 Base-Catalyzed Keto-EnolTautomerism 1047 Acid-Catalyzed Keto-EnolTautomerism 1047 Base-Promoted Halogenation 1054 Final Steps of the Haloform Reaction 1056 Acid-Catalyzed Alpha Halogenation 1058 Acid-Catalyzed Aldol Condensation 1063 1,2-Addition and 1,4-Addition (Conjugate Addition) 1085... 

The aldol reaction involves the substitution of an ct-hydrogen by the carbonyl carbon of another carbonyl compound, thereby creating a 3-hydroxycarbonyl product. Eq. 11.13 shows the coupling of two aldehydes, while Eq. 11.14 shows the coupling of two ketones. The reaction is similar to the alkylation and halogenation of an enolate, except that now the electrophile is another carbonyl compound, and so we have nucleophilic addition to a carbonyl as well as substitution on an a-carbon. As with other reactions we have seen in this section, the aldol reaction can proceed via an enol or an enolate. However, the most common pathway, and the one we will emphasize here, makes use of an enolate and so is base-catalyzed. With prolonged treatment in acid or base, the p-hydroxycarbonyl products will dehydrate to form a,(3-unsaturated carbonyl structures. 

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