Ketones base-promoted halogenation

With most ketones, base-promoted halogenation continues until the a carbon atom is completely halogenated. Methyl ketones have three a protons on the methyl carbon, and they undergo halogenation three times to give trihalomethyl ketones. 

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... 

The base-promoted halogenation takes place by a nucleophilic attack of an enolate ion on the electrophilic halogen molecule. The products are the halogenated ketone and a halide ion. 

Because of this tendency for multiple halogenation, base-promoted halogenation is rarely used for the preparation of monohalo ketones. The acid-catalyzed procedure (discussed in Section 22-5C) is preferred. 

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... 

Problem 21.5 Show in detail exactly how each of the following facts provides evidence for the carbanion mechanism of base-promoted halogenation of ketones. 

Base-promoted halogenation of aldehydes and ketones is little used ir, practice because it s difficult to stop the reaction at the monosubstituted product. An -halogenated ketone is generally more acidic than the star ing, unsubstituted ketone because of the electron-withdrawing inductiv effect of the halogen atom. Thus, monohaiogenated products are themselvi rapidly turned into enoiate ions and further halogcnated. 

In contrast, base-promoted halogenation tends to occur on the less substituted a carbon atom. For example, base-promoted iodination of methyl alkyl ketones leads initially to the iodomethyl alkyl ketone. Further reaction leads to the a,a-diiodo-, then to the a,a,a-triiodoketone, and then to iodoform and a carboxylate ion by the haloform reaction (Figure 7.10). 

Two factors could contribute to the observed regiochemistry of base-promoted halogenation of ketones. One is a kinetic preference for formation of the less substituted enolate. Evidence for this effect can be seen in the rate constants for base-catalyzed iodination of phenyl alkyl ketones with the structure C6H5COCHR1R2, which are found to decrease with increasing alkyl substitution (Table 7.8). ... 

A second possible explanation for the regiochemistry of base-promoted halogenation of ketones is a greater thermodynamic stability of the less substituted enolate, and there is evidence suggesting that this may be the case for some enolates. House and Kramar investigated the equilibria... 

Base-promoted halogenation of methyl ketones leads to an interesting result known as the haUtform reaction (See Exercises.). 

Base-promoted halogenation of a methyl ketone (or aldehyde) gives rise to the following... 

As an example of enolate-ion reactivity, aldehydes and ketones undergo base-promoted o halogenation. Even relatively weak bases such as hydroxide ion are effective for halogenation because it s not necessary to convert the ketone completely into its enolate ion. As soon as a small amount of enolate is generated, it reacts immediately with the halogen, removing it from the reaction and driving the equilibrium for further enolate ion formation. 

Problem 22.9 Why do you suppose ketone halogenations in acidic media referred to as being ackl-calalyzed, whereas halogenations in basic media are base-promoted In other words, why is a full equivalent of base required for halogenation ... 

Substituent effects on rate constants of base-promoted ionisation of ketones have led to the conclusion that an electron-withdrawing substituent increases the rate of ionisation, in agreement with the anionic character of the transition state. This is based chiefly on studies on halogenation and isotope exchange of aromatic ketones. Data on p-values observed by plotting ionisation rate constants versus Hammett -parameters (Table 3) for substituted... 

Q Give mechanisms for the acid-catalyzed and base-promoted alpha halogenations Problems 22-68 and 69 of ketones. Explain why multiple halogenations are common with basic catalysis, and give a mechanism for the haloform reaction. 

Acids, like bases, speed up the halogenation of ketones. Acids are not, however, consumed, and hence we may properly speak of Sicid-catalyzed halogenation (as contrasted to basQ-promoted halogenation). Although the reaction is not. 

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