Alpha Halogenation of Aldehydes and Ketones

Aldehydes and ketones can be halogenated at their a positions by reaction with CI2, Br-2, or I2 in acidic solution. Bromine in acetic acid solvent is often used. 

Additional evidence is that acid-catalyzed halogenations show second-order kinetics and follow the rate law 

In other words, the rate of halogenation depends only on the concentrations of ketone and acid, and is independent of halogen concentration. Halogen is not involved in the rate-limiting step. 

A final piece of evidence comes from deuterium-exchange experiments. If an aldehyde or ketone is treated with DgO instead of HsO , the acidic a hydrogens are replaced by deuterium. For a given ketone, the rate of deuterium exchange is identical to the rate of halogenation, indicating that the same intermediate is involved in both processes. That common intermediate can only be an enol (see the reaction mechanism at the top of p. 909). 

The carbonyl oxygen atom is prolonated by acid catalyst. 

Remarkably, ketone halogenation also occurs in biological systems, particularly in marine alga, wdiere dibromoacetaldehyde, bromoacetone, 1,1,1-tri-bromoacetone, and other related compounds have been found. 

O Loss of an acidic proton from the alpha carbon takes place in the normal way to yield an enol intermediate. 

I An electron pair from the enol attacks bromine, giving an intermediate cation that is stabilized by resonance between two forms. 

O Loss of the -OH proton then gives the alpha-halogenated product and generates more acid catalyst. 

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Alpha halogenation of aldehydes and ketones occurs readily under basic conditions and does not stop with the replacement of a single hydrogen atom. All a-hydrogen atoms are substituted. 

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). 

Halogenation of saturated aldehydes and ketones usually occurs exclusively by replacement of hydrogens alpha to the carbonyl group ... 

Carbonyl compounds are in a rapid equilibrium with their cnols, a process called keto-enol tautomerism. Although enol tautomers arc normally present to only a small extent at equilibrium and can t usually be isolated in pure form, they nevertheless contain a highly nucleophilic double bond and react with electrophiles. P or example, aldehydes and ketones are rapidly halogenated at the a position by reaction with CI2 Br2, or I2 in acetic acid solution. Alpha bromination of carboxylic acids can be similarly accomplished by the Hell-Volhard-Zelinskii (HVZ) reaction, in which an acid is treated with Bt2 and PBrThe a--halogenated inoducts can then undergo base-induced E2 elimination to yield a,/3-un.salurated carbonyl compounds. 

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... 

Alpha halogenation, as described in the previous section, occurs readily with ketones and aldehydes, but not with carboxylic acids, esters, or amides. This is likely due to the fact that these functional groups are not readily converted to their corresponding enols. Nevertheless, carboxylic acids do undergo alpha halogenation when treated with bromine in the presence of PBt3. 

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