Hypohalous acids formation

However, as HOX is consumed, hydrolysis is retarded because of build-up of free amine. Consumption of hypohalous acid through reaction with HX can result in formation of elemental halogen HOX + + X X2 + H2 O (1—3). The tendency for halogen formation is much greater for HOBr and... 

Formation of oxiranes on the sterically more hindered side of the steroid ring system is usually carried out via /raw -halohydrins which afford oxiranes on treatment with base (c -Halohydrins yield ketones on exposure to base). Two general methods are available for the synthesis of tm s-halohydrins (1) the reduction of a-halo ketones and (2) the addition of a hypohalous acid to unsaturated steroids. 

Addition of Hypohalous Acids to Alkenes Halohydrin Formation... 

Yet another example of an electrophilic addition is the reaction of alkenes with the hypohalous acids HO—Cl or HO-Br to yield 1,2-halo alcohols, called halohydrins. Halohydrin formation doesn t take place by direct reaction of an alkene with HOBr or HOC1, however. Rather, the addition is done indirectly by reaction of the alkene with either Br2 or Cl2 in the presence of water. 

In cooling water applications, great importance is placed on activity against Legionella pneumophila, the causative agent of Legionnaires disease. Bromochloro dimethylhydantoin has been shown to rapidly hydrolyze in water with the formation of hypobromous acid (21). The pKa of hypobromous acid is 8.8, whereas the pK of hypochlorous acid is 7.4. Because the undissociated hypohalous acid is the active biocide, the hypobromous-generating chemical is more active in alkaline systems. 

Despite that the MPO-catalyzed oxidation of halides seems to employ the same mechanisms active in primary production of the respective hypohalous acids, the final products of peptide and protein oxidation vary, depending on the halide ion employed iodides and bromides when used as substrates yield stable bromo-and iodotyrosine derivatives, whereas direct chlorination of the available free amino moieties and semistable chloramines formation predominate when Cl is oxidized as the substrate (S54, Z3). The chlorination is a unique function of polymorphonuclear neutrophilic leukocytes (W6, Z2). 

The diastereoselectivity of the addition of hypohalous acids and esters to alkenes is potentially even more susceptible to polar effects than peracid epoxidations124 they correlate to the electronegativity of the halogen and of the oxygen substituent. The derived epoxide normally has the opposite configuration to that resulting from the polar effect on peracid epoxidation, e.g., formation of the epoxide 2 with various acyl hypohalites38. 

When bromine or chlorine is added to water, physical solution occurs followed by hydrolysis and formation of the corresponding hypohalous acid. In strongly acid solution... 

The formation of the intermediate OI2 is expected over HOIO for several reasons. First, the reactivity of hypohalous acids is usually as OH and X+ (51,... 

Nitryl chloride, formed from peroxynitrite and HOCl is also capable of nitrating, chlorinating and hydroxylating tyrosine [ 116]. However, the reduction of nitrotyrosine by hypohalous acid has also been demonstrated. Several recent studies indicate that peroxynitrite can lead to generation of both nitrated and hydroxylated phenylalanine residues. The formation of 3-nitrotyrosine and 4-nitrophenylalanine was favoured over the hydroxylation reaction when phenylalanine was treated with peroxy nitrite in vitro [117]. 

Enzymatic halogenation catalyzed by haloperoxidases and perhydrolases involves the oxidation of halide ions to a halonium ion species which leads to the formation of hypohalous acids (Fig. 16.9-1). The products obtained by enzymatic halogenation with these enzymes are the same as the products obtained by chemical electrophilic halogenation with hypohalous acids. The differences in the para ortho ratios in the halogenation of some aromatic compounds could be due to a mixture of halogenation at or near the active site and in solution. 

Figure 1.57 Reaction mechanisms of heme-type haloperoxidases showing the formation hypohalous acids (HOX X = Cl, Br, or I).

Haloperoxidases have been shown to transform alkenes by a formal addition of hypohalous acid to produce halohydrins. The reaction mechanism of enzymatic halogenatitHi has been debated for some time and it is now accepted that it proceeds via a halonium intermediate [1770, 1771], similar to the chemical formation of halohydrins (Scheme 2.228). The former species is derived from hypohalous acid or molecular halogen, which is in turn produced by the enzyme via oxidation of halide [1772]. In support of this, a HOCl-adduct of Fe -protoporphyrin IX was identified as a direct enzyme-halogen intermediate involved in chloroperoxidase-catalyzed halogenaticHi [1773]. 

The mechanism by which hypohalites oxidize alcohols probably involves initial formation of an alkyl hypohalite (Eq. 16.16). This product arises from reaction of the alcohol with the hypohalous acid that is in equilibrium with hypohalite ion in aqueous medium (Eq. 16.15). Base-promoted E2 elimination of the elements of H-X from the alkyl hypochlorite leads directly to either an aldehyde or ketone. The advantage of using hypohalite as an oxidant is immediately obvious upon examining Equation 16.16. The inorganic by-product derived from the oxidant is a halide salt that can be safely flushed down the drain. Reactions that do not produce toxic by-products are environmentally friendly and are now commonly referred to as "Green Chemistry." (See the Historical Highlight at the end of this chapter.)... 

Some side reactions may complicate the oxidation of a primary alcohol to an aldehyde using hypohalous acid. For example, an aldehyde may undergo reaction with an additional equivalent of hypohalite to form a carboxylic acid (Eq. 16.17), a process that may be initiated by acid-catalyzed formation of the hydrate of the intermediate aldehyde as shown in Equation 16.18. Subsequent steps in the oxidation are then analogous to those for converting an alcohol to an aldehyde or ketone (Eq. 16.16). It may be difficult to suppress this further oxidation, so unless carboxylic acids are the desired products, the use of hypohalite as an oxidant is limited to the conversion of secondary alcohols to ketones. 

The other hypohalous acids are all very reactive oxidizing agents that are relatively unstable. They are most conveniently prepared by the disproportionation of the parent halogen, X2, in water [Eq. (14)]. Addition of HgO or Ag20 precipitates the halide ion and shifts the equilibrium so as to favor additional hypohalite formation. Attempts to prepare pure samples from aqueous solution lead to decomposition. 

Oxidation in Add Solutions. In acid solutions the active oxidant is the free halogen or the hypohalous acid. As noted above, the proportions of these potential forms of the oxidant vary with the acidity of the solution and the nature of the halogen. However, unless a buffer or neutralizing substance is present, the solution will become strongly acid as a result of the formation of hydrohalic acid. 

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