Enols alpha halogenation

Mechanism 22-4 Base-Catalyzed Keto-EnolTautomerism 1047 Mechanism 22-5 Acid-Catalyzed Keto-EnolTautomerism 1047 22-3 Alkylation of Enolate Ions 1050 22-4 Formation and Alkylation of Enamines 1051 22-5 Alpha Halogenation of Ketones 1054... 

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. 

The base abstracts a proton to form the enolate, which then functions as a nucleophile and undergoes alpha halogenation. 

This small amount of enol is able to react as a nucleophile and attack some electrophile. After the enol attacks the electrophile, the keto-enol equilibrium is re-established by producing some more enol (to account for the enol that disappeared as a result of the reaction). Slowly but surely, most of the ketone molecules end up converting into enols and reacting with the electrophile. The most common example is alpha-halogenation, which can occur when a ketone is treated with Br2 in aqueous acid (HsO ) to generate an a-halo ketone ... 

Based on the energy diagram in CTQ 11, which is rate-limiting in acid-catalyzed alpha-halogenation, keto-enol tautomerization or halogenation (circle one)... 

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. 

Z3.3. The Feist-Benary Furan Synthesis. In this synthesis, an aldol-type carbonyl-carbanion condensation and a halogen displacement by an enol are employed to bring two molecules together in a ring stmc-ture, and in this sense it resembles the Knorr synthesis. The reactants are an alpha-haloketone and a ketoester (like ethyl acetoacetate). The mechanistic details remain unclear, but a logical mechanism is shown in Scheme 4.34. This assumes the carbonyl condensation occurs first before the halogen displacement, but the reverse may be tme. 

If we want to halogenate the alpha position of a carboxylic acid, it is possible, but it will require some extra steps. First, we must convert the carboxyhc acid into an acid halide. We do this because the enol of an acid halide will rapidly attack a halogen. Then, in the end, we just convert the acid hahde back into a carboxylic acid ... 

---