Halogenation of phenols

Beside being acidic, a significant industrial chemical property of phenol is the extremely high reactivity of its ring toward electrophilic substitution. If steric conditions permit, the substitution leads first to the formation of the 2- or 4-mono derivative, then to the 2,4- or 2,6-diderivative, and finally to the 2,4,6-triderivative. The halogenation of phenol produces mono-, di-, and tribal ophenols. 

Wannstedt, C., Rotella, D., and Siuda, J.F. Chloroperoxidase mediated halogenation of phenols. Bull. Environ. Contam. Toxicol, a 2) 282-287, 1990. 

For a review of the halogenation of phenols, see Brittain de la Mare, in Patai Rappoport The Chemistry of... 

The ability of compounds with a quinonic structure to form donor-acceptor interactions and CT complexes is useful in regioselective halogenation of phenol (or naphthols and their derivatives). 

Generally, electrophilic halogenation of phenols leads to the corresponding ortho-and para-substituted products. The synthesis of meta-substituted products is considered difficult.474,555... 

The halogenation of phenols and aromatic amines in aqueous solution also provides evidence for diffusion control, but the interpretation is complicated by the fact that either the formation of the o-complex or the proton loss from the (7-complex can be rate-determining. The reaction path for the halogenation of aromatic amines in aqueous acids is believed to be that shown for N,N-dialkyl anilines in Scheme 9. Where the formation of the o-complex is rate-determining, the kinetic form for attack by the molecular halogen is given by (39). In this equation, the observed rate coefficient (k ) is related to the rate coefficient for the reaction of the amine molecule (k) by (40), where KSH+ is the... 

Difunctional compounds have been prepared by the nuclear halogenation of phenols, acids, amines, cyanides, and nitro compounds. Aromatic esters containing nuclear halogen atoms ate best prepared by halogenating the acid chloride followed by esterification. The direct halogenations of ethers (method 65), aldehydes and ketones (method 66), and acids and esters (method 67) are discussed later. 

Many derivatives of phenol are now made by a synthetic process. A combination of alkyl or aryl substitution and halogenation of phenolic compounds has produced useful derivatives. Two of the most... 

Although a stable dibromide cannot be isolated for a similar study of the bromination of benzene, the kinetics of the iodine catalyzed bromina-tion of benzene is identical with that of phenanthrene.26 Consequently it is very probable that the mechanism of the halogenation of benzene is the same as that proposed for phenanthrene. The kinetics of chlorination,27 bromination,28 and iodination by iodine chloride29 are also in agreement with this interpretation. The halogenation of phenols, however, appears to be a different, more complex process. 0... 

The electrophilic halogenation of phenols give rise to mixtures of ortho- and para-substituted phenols. Phenols are more reactive than aUcylaromatics in these reactions due to the enhanced resonance stabilization of the carbocationic intermediates (equation 72). However, in superacidic solutions, the oxygen protonation of the phenols leads to the deactivated substrate for halogenation and meta-halo products are obtained (equation 73). ... 

Halogenation of phenols is faster in polar solvents due to the dissociation of phenol, with phenoxide ions being more susceptible to electrophilic attack as they are more electron-rich. 

GUY LEMAIRE GUETTE Phenol Chlorination Regloselective ortho or para halogenation of phenols and the corresponding ethers (only para) by hexachloro cyclohexadene 2 or 3 respectively. 

A potentially important appUcation of micelles or similar species is the extent to which they can control product composition. The abiUty of cationic micelles to speed E2 eliminations and inhibit S l reactions has been cited [53-55]. But in addition micelles can control isomer distribution to some extent, as in the halogenation of phenolic ethers [179]. In another example Sukenik and coworkers have used micelles to mediate the isomeric composition of the products of oxymercuration of alkenes [180],... 

Regioselective para-halogenation of phenols in good yield and... 

Halogenation of phenol also leads to phenol derivatives which are much more effective than the starting substance. At the same time, the dissociation constant increases with an increase in the number of halogen atoms, i.e. the acidic character of the phenol derivatives becomes more distinctive. The combination of alkylation and halogenation (the latter with preference in the p-position) has led to microbicides which have attained great practical significance as substances for the protection of materials and disinfection, e.g. p-chloro-o-benzyl phenol, p-chloro-m-cresol, p-chloro-/M-xylenol. 

Halophenols have broad applications in the synthesis of oxygen-containing heterocycles. Typically, 2-halophenol can be prepared by the halogenation of phenols. Then, 2-halophenol can be used for the preparation of the other derivatives. Notably, 2-halophenol also acts as the precursor for aiynes by activation of the C-O bond. 

This should not be confused with the lower pK value that results upon halogenation of phenol (see Table 2.1), for this again represents inductive pull. Nonetheless, resonance effects can extend themselves to other important examples as is noted by a comparison of the basicity of cyclohexylamine and aniline. The former has a pK typical of an organic amine (Table 2.1), but the latter is considerably more acidic. That is because at any given time the electron density of the amino function of aniline is much less than that of cyclohexylamine. The nonbonding electrons are smeared into the aromatic ring via resonance ... 

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