Haloform reaction mechanism

The methyl ketone shown in the example can enolize in only one direction and typifies the kind of reactant that can be converted to a carboxylic acid in synthetically acceptable yield by the haloform reaction. Mechanism 20.4 describes how this cleavage occurs. 

The mechanism of the haloform reaction begins with a halogenation via the eno late The electron attracting effect of an a halogen increases the acidity of the protons on the carbon to which it is bonded making each subsequent halogenation at that car bon faster than the preceding one... 

The oxidation of aldehydes to carboxylic acids can proceed by a nucleophilic mechanism, but more often it does not. The reaction is considered in Chapter 14 (14-6). Basic cleavage of (3-keto esters and the haloform reaction could be considered at this point, but they are also electrophilic substitutions and are treated in Chapter 12 (12-41 and 12-42). 

Figure 11-9 illustrates the mechanism for the haloform reaction. The mechanism involves a repeated series of base attacks (removal of an a-hydrogen) followed by the reaction with the halogen until all three a-hydrogen atoms are replaced. Then the base attacks the carbonyl carbon to induce the loss of a carbanion Q.CXf. The highly reactive carbanion quickly attacks and removes the hydrogen from the carboxylic acid group. 

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... 

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. 

In the haloform reaction, the three H atoms of the CH3 group are successively replaced by X to form an intermediate that is oxidatively cleaved with base. Mechanism 23.5 is written with I2 as halogen, forming CHI3 (iodoform) as product. 

The mechanism of the haloform reaction has been extensively studied, and it can be concluded that it is a very complex process. The exact mechanistic pathway is dependent on the structure of the substrate and the specific reaction conditions. The scheme depicts the oxidation of a methyl carbinol to the corresponding methyl ketone via an organic hypohalite. The methyl ketone then undergoes deprotonation, and three sequential a-halogenations take place to afford the trihalomethyl ketone. This compound undergoes rapid hydrolysis to afford the haloform and a carboxylate. 

Bartlett, P. D. Enolization as directed by acid and basic catalysts. II. Enolic mechanism of the haloform reaction. J. Am. Chem. Soc. 1934,... 

The mechanism of the Haloform reaction involves base-catalyzed generation of an enolate 6 followed by in situ halogenation to afford an a-haloketone 7. Two subsequent repetitions afford trihaloketone 8, which then is susceptible to cleavage by alkali to furnish carboxylic acid 5 and haloform 4, after acidification. 

Several reported kinetic studies shed light on the various steps in the Haloform reaction. Bartlett showed in 1934 that the reaction of acetone with strong alkaline solutions of hypobromite and hypoiodite involves enolization of acetone as the ratedetermining step, but the rate of the same reaction with alkaline hypochlorite involves as the slow step reaction of acetone enol with hypochlorite.15 Likewise, the mechanism of the iodoform reaction and its optimization for quantitative analysis have received much scrutiny16 including studies of acetone-1-C-l4 7 and deuterated acetone18 for isotope... 

PROBABLE FATE photolysis, could be important, direct photolysis does not occui below the ozone layer, if released to air, the transformation process in the troposphere is reactior with hydroxyl radicals, with an estimated half-life of 6.65 months oxidation, could occur hydrolysis too slow to be important volatilization volatilization has been demonstrated, probabl> an important transport mechanism, if released to water or soil, volatilization will be the dominani fate process, volatilization half-life from rivers and streams 33 min to 12 days with a typical half-life of 35 hrs sorption no information, but adsorption onto activated carbon has been demonstrated biological processes moderate potential for bioaccumulation, metabolization by some aquatic life is known to occur, anaerobic biodegradation may be the major removal process in aquatic regions where volatilization is not possible other reactions/interactions may be formed by a haloform reaction following chlorination of drinking water if sufficient bromide is present... 

Figure 5.5. Mechanism of the haloform reaction with methyl ketones. From Morris and Baum (1978). Reprinted by permission of Lewis Publishers.

Mechanism 20.7 outlines the steps involved in the haloform cleavage of a methyl ketone. The boxed essay The Haloform Reaction and the Biosynthesis of Trihalo-methanes describes its involvement as an environmental source of chloroform and bromoform. 

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