Basic hydrolysis of haloforms

Although relevant observations had been made as early as 1862, it was not until 1950 that the mechanism of the basic hydrolysis of haloforms was elucidated by Hine and his co-workers. Today the reactions of haloforms with base are the most thoroughly investigated examples of a-elirnination. 

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In solution, dihalocarbenes are often produced from the basic hydrolysis of haloforms ... 

Hine, J., Dowell, A. M. Singley, J. E. (1956). Carbon dihalides as intermediates in the basic hydrolysis of haloforms. IV Relative reactivities of haloforms. Journal of the American Chemical Society, 78, 479-82. 

The basic hydrolysis of haloforms is first-order with respect to both haloform and hydroxide ion . Several arguments eliminate nucleophilic attack of hydroxide ion on haloform, Sn2 displacement (22), as a possible mechanism. 

KINETIC parameters FOR THE BASIC HYDROLYSIS OF HALOFORMS AND RELATED COMPOUNDS IN 66.7% DlOX AN-WATER ... 

Accepting the carbene mechanism (23) as generally valid, the over-all rate coefficients for the basic hydrolysis of haloforms may be expressed in terms of the individual steps as follows. 

Hine and co-workers have since shown this scheme to be general for a variety of fluorine-free haloforms, and more recent work by Robinson has led to an improved rate expression for the basic hydrolysis of... 

When I was a first year graduate student at the University of Chicago in 1961, Professor M.J.S. Dewar asked me to prepare a review of Jack nine s pioneering studies of haloform hydrolysis.[1] Hine had demonstrated that the basic hydrolysis of (e.g.) chloroform proceeded via dichlorocarbene Eq. 1-3. 

The reaction of 2- and 4-hydroxyadamantane-l-carboxylic esters with dibromo-carbene produces the corresponding 2- and 4-bromo derivatives (10-20%). Slow hydrolysis of the ester groups may also occur under the basic conditions. l-Acetyl-4-hydroxyadamantane yields 4-bromoadamantane-l -carboxylic acid (37%), as a result of a concomitant reaction with dibromocarbene and a haloform-type reaction [8]. 

The replacement of an a hydrogen of an alkyl halide by halogen decreases Sn2 reactivity. Chloroform, however, is about one thousandfold more reactive in basic hydrolysis than methylene chloride . Every bromine-containing halo-form studied (Table 7) is at least 600 times as reactive toward hydroxide ions in 66.7% aqueous dioxan as methylene bromide ". Toward weakly basic nucleophiles, such as thiophenoxide ion, the predicted reactivity order is obeyed haloforms have been found to be less reactive than the corresponding methylene halides . The reaction of haloforms with sodium thiophenoxide is strongly accelerated, however, by the presence of hydroxide ions - . These observations are quite unexplainable in terms of scheme (22). 

As mentioned above, the replacement of bromine or chlorine in haloforms by fluorine decreases the rate coefficient of carbanion formation, k. The overall rate of basic hydrolysis, however, increases because fluorine stabilizes the carbene intermediate. Because of the increase in /cj, the ratio /ca/it-i of halo-forms CHX2F is in the order of 2-10. 

The oxidation of a methyl ketone to a carboxylic acid can be effected by the use of the haloform reaction. This involves treatment of the methyl ketone with an alkaline hypohalite reagent. A trihalomethyl ketone is initially formed which then undergoes hydrolysis under the basic conditions used. 

The simplest halogen substituted carbon acids which have been studied in detail are the haloforms CHX3 where X = F, Cl, Br, or I. The low acidity of the haloforms combined with their ready hydrolysis in strongly basic solutions means that equilibrium acidities cannot easily be measured. 

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