Base-promoted halogenation, of aldehydes and 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. 

Halogenation of aldehydes and ketones occurs under both basic and aci( conditions. As you might expect, the base-promoted reaction occurs throi an enoiate ion intermediate. Even relatively weak bases such as hydro ion are effective for halogenation because it s not necessary to convert, ketone completely into its enoiate ion. As soon as a small amount of eno-late is generated, it reacts immediately with the halogen. 

The slow step in base-promoted a-halogenation is removal of an a-hydrogen by base to form an enolate anion, which then reacts with halogen by nucleophilic displacement to form the final product. This procedure for a-halogenation produces HX as a by-product, and in order to keep the solution basic, it is necessary to add slightly more than one mole of base per mole of aldehyde or ketone. Because base is a reactant required in equimolar amounts, we say that this reaction is base-promoted rather than base-catalyzed. 

Generally, isolated olefinic bonds will not escape attack by these reagents. However, in certain cases where the rate of hydroxyl oxidation is relatively fast, as with allylic alcohols, an isolated double bond will survive. Thepresence of other nucleophilic centers in the molecule, such as primary and secondary amines, sulfides, enol ethers and activated aromatic systems, will generate undesirable side reactions, but aldehydes, esters, ethers, ketals and acetals are generally stable under neutral or basic conditions. Halogenation of the product ketone can become but is not always a problem when base is not included in the reaction mixture. The generated acid can promote formation of an enol which in turn may compete favorably with the alcohol for the oxidant. 

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 Reformatsky reaction is the reaction of an a-halo ester with an aldehyde or ketone in the presence of zinc metal as shown in Scheme 1. The usual product of the reaction is a -hydroxy ester, which may be dehydrated in subsequent steps to give an unsaturated ester. A zinc ester enolate (1), the so-called Reformatsky reagent, is an intermediate in the reaction and the sequence is thus classified as an aldol condensation. Compared to the usual base-promoted aldol procedures, the distinguishing features of the Reformatsky reaction are the use of a metal-halogen redox reaction rather than an acid-base reaction to form the enolate, and the fact that the counterion of the enolate is zinc. 

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