Base-Promoted Halogenation

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. 

By the same token, in base-promoted E2 dehydrohalogenations, the rate of elimination of the halogen as a halide ion is expected to be I > Br > Cl F This element effect has indeed been documented in many instances, a few examples of which are listed in Table I... 

Table 1. Relative Rates of Base-Promoted Dehydrohalogenations of Halogenated Compounds...

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 ... 

The base-promoted dehydrohalogenation of vinyl or allylic halides affords poor yields of allenes because of the competing side reaction leading to acetylenes [21,22], The presence of tertiary hydrogens a to the halogen also helps to... 

The base-promoted a eliminations of chloroform or bromoform provide a simple method for the production of dihalocarbenes. These add readily to olefinic double bonds to give 1,1-dihalocyclopropanes. The halogens can be removed (one or both) by reduction the most common method is to use tri-n-butyltin hydride. 

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... 

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. 

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. 

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. 

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... 

Halogenation in basic medium is base-promoted because a stoichiometric amount of base is consumed ... 

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. 

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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