Haloforms acidity

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 haloform reaction is sometimes used for the preparation of carboxylic acids from methyl ketones... 

The methyl ketone shown in the example can enohze in only one direction and typifies the kind of reactant that can be converted to a carboxylic acid in synthetically accept able yield by the haloform reaction When C 3 of a methyl ketone bears enolizable hydro O... 

In addition to the applications indicated on p. 858. hypohalous acids are useful halogenating agents for Ixjth aromatic and aliphatic compounds. HOBr and HOI are usually generated in silii. The ease of aromatic halogenation increa.ses in the sequence OCl < OBr < Ol and is facilitated by salts of Pb or Ag. Another well-known reaction of hypohalites is their cleavage of methyl ketones to form carboxylates and haloform ... 

Fluorine cannot be used, although trifluoroketones can be cleaved into carboxylate and trifluoromethane. The haloform reaction can be conducted under mild conditions—at temperatures ranging from 0-10 °C—in good yields even a sensitive starting material like methylvinylketone can be converted into acrylic acid in good yield. 

Haloform reaction (Section 22.6) The reaction of a methyl ketone with halogen and base to yield a haloform (CHX3) and a carboxylic acid. 

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). 

An overview of the reactions involving trihalomethanes (haloforms) CHXYZ, where X, Y, and Z are halogen atoms, has been given in the context of ozone depletion (Hayman and Derwent 1997). Interest in the formation of trichloroacetaldehyde formed from trichloroethane and tetrachloroethene is heightened by the phytotoxicity of trichloroacetic acid (Frank et al. 1994), and by its occurrence in rainwater that seems to be a major source of this contaminant (Muller et al. 1996). The situation in Japan seems, however, to underscore the possible significance of other sources including chlorinated wastewater (Hashimoto et al. 1998). Whereas there is no doubt about the occurrence of trichloroacetic acid in rainwater (Stidson et al. 2004), its major source is unresolved since questions remain on the rate of hydrolysis of trichloroacetaldehyde (Jordan et al. 1999). 

Thus acid chlorides and anhydrides react readily with ROH and NH3 to yield esters and amides, respectively, while esters react with NH3 or amines to give amides, but the simple reversal of any of these reactions on an amide, though not impossible, is usually pretty difficult. The relative reactivity will also depend on both the electronic and, more particularly, the steric effect of R. A slightly unusual leaving group is eCX3 (e.g. eCI3) in the haloform (158) reaction (cf. p. 297) ... 

It is also found, in contrast to bromination under base-catalysed conditions, that introduction of a further bromine into a mono-bromoketone is more difficult than was introduction of the initial one. It is thus normally possible, under acid conditions, to stop bromination so as to obtain the mono-bromo product, e.g. (107), preparatively. This is, of course, in contrast to under base conditions, where further bromination cannot be prevented and is followed, in suitable cases, by haloform cleavage (p. 296). 

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]. 

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. 

The haloform reaction is a useful method of preparing a carboxylic acid (carboxylate ion) with one less carbon. It is one of the very few cases where carbanion loss occurs. It s only possible because the three halogen atoms are capable of stabilizing the negative charge. 

Problem 16.8 (a) Why isn t 2-naphthoic acid made from 2-chloronaphthalene (f>) How is 2-naphthoic acid prepared in a haloform reaction M... 

---