Phenols monobromination

A hydroxyl group is a very powerful activating substituent, and electrophilic aromatic substitution in phenols occurs far- faster, and under milder conditions, than in benzene. The first entry in Table 24.4, for exfflnple, shows the monobromination of phenol in high yield at low temperature and in the absence of any catalyst. In this case, the reaction was carried out in the nonpolar- solvent 1,2-dichloroethane. In polar- solvents such as water it is difficult to limit the bromination of phenols to monosubstitution. In the following exfflnple, all three positions that are ortho or para to the hydroxyl undergo rapid substitution ... 

With 3-methylphenol (meto-cresol), around 8 % of dibromo products result when one equivalent of brominating agent is used, and this rises to 23 % of dibromo products on attempted monobromination of 3,5-dimethylphenol with 1 molar equivalent of resin. Nevertheless, the good yields of products obtained from the mono-substituted phenols tried demonstrate that this is a powerful new synthetic method for the organic chemist. 

This procedure is described by Lock 2 a modification using a small amount of phenol has been published.3 The patent literature discloses the use of a tertiary amine, such as pyridine, and its combination with other solvents for the monobromination of pyrene with elemental bromine.4 Brominating agents, such as N-bromosuccinimide5 and N-bromohydantoins,6 have also been used. 

Monobromination is achieved with nonpolar solvents such as CS to decrease the electrophilici-ty of Brj and also to minimize phenol ionization. 

Examjdes.—Aniline is rapidly tribrominated at room temperature, the end point is very sharp, and this estimation of aniline is preferable to the nitrous acid method. At ordinary temperature ortho- and para-toluidines are dibrominated and meta-toluidine is tribrominated. Dimethylaniline is monobrominated at 0°—5°, dibrominated at 40°—50° and tribrominated at 60°—70°, an interesting example of the effect of temperature. Sulphanilic acid at 60°—70° yields tribromoaniline, and at this temperature p-nitroaniline reacts quantitatively. Phenol at about 22° yields tribromophenol. For reference to the estimation of m-diamines, m-dihydroxy compounds, R salt, cresols, p nitroaniline, diphenylamine, p-nitrophenol, and other notes, see J. S. C. I., 41, 161. 

The monobromination of phenol can, however, be achieved by using solutions of bromine in non-polar solvents such as carbon disulphide and carbon tetrachloride at low temperature (0-5 °C). The product is almost exclusively the para isomer (Expt 6.105). 

Hydroxypyridines react very much like phenols they are not subject to keto-enol tautomerism to a significant degree. In aqueous alkali the oxyanion is the reactive species with bromine entering positions ortho and para to that substituent. It has proved possible to achieve a high proportion of monobromination by the use of one molar equivalent of bromine. As the proportion of bromine to substrate was increased more... 

The photocatalytic ability of POM to induce bromide-assisted functionalization process was also studied by Molinari et al. [27] in the bromination of some aromatics and alkenes. They reported the possibility to convert phenol and anisole to the corresponding monobrominated derivates and a wide range of cydoalkenes to dibromides and bromohydrins, the last ones as intermediates for the formation of epoxides. 

Vomicine is easily monobrominated, probably in position 3, ortho to the phenolic group (187). Mononitration may be achieved with dilute aqueous nitric acid, but is difficult and gives varying yields dihydro-vomicine on the other hand gives a dinitro derivative in very good yield (194). Nitric-concentrated sulfuric acid mixture at —18° oxidizes the aromatic ring (see Section IV, E, 2). 

Bromination ofarenes. NBS in DMF is useful for monobromination of reactive arenes and also of phenols and anilines. The reaction is not useful for monobromination of o- and p-hydroxyphenols or for dianilines. Some compounds (and the yields) prepared in this way are listed. ... 

A Under normal conditions, phenol brominates rapidly to give 2.4,6-tribromophenol and even under mild conditions with bromine in acetic acid it gives /7-bromophenol. Consequently, the reactivity of the ring has to be diminshed and the para position protected. In order to achieve this, phenol is first sulfonated to give the 2,4-disul-fonate. This is then monobrominated and the sulfonate groups are removed by heating with water. 

This reagent is useful for selective monobromination of phenols and of aromatic amines, predominantly in the para position. Methylene chloride and chloroform are used as solvents. Yields are generally higher than 90%. 

Bromination. Phenols and anilines undergo monobromination at room temperature in good yields. 

There are numerous procedures for the bromination of phenolic compounds and the regioselectivity in these reactions has been frequently achieved by varying the nature of the solvent system. Controlled monobromination of phenols can be achieved using N-bromosuccinimide (MBS) on silica gel . ... 

Interestingly, the dibrominated compound could be methylated by derivatisation with trimethylsulphonium hydroxid (TMSH) forming the corresponding methylether. The mass spectra are presented in Fig. 7. In contrast, the monobrominated phenol remained unaffected as the result of less acidity due to the lower degree of bromine substitution. 

The preparation of mono- and di-halogenated derivatives of phenols and aromatic amines is of particular preparative interest. Mild conditions often suffice for introduction of, especially, chlorine or bromine, but also of iodine, at all the favored positions, even when that is not desired. Monochlorination or monobromination of phenols by Cl2 or Br2 occurs mainly at position 4 in the cold but mainly at position 2 at 150-180°. 

Dioxan Br2, alone or in ether or dioxan, can be used to monobrominate phenol, polyhydric phenols, aryl ethers, and salicyclic acid.452... 

Monobromination of phenol can be achieved by carrying out the reaction in carbon disulfide at a low temperature, conditions that reduce the electrophilic reactivity of bromine. The major product is the para isomer ... 

In macroscopic chemistry, the experimental procedures for the bromination of aromatic compounds depend greatly on the nature and reactivity of the starting material. Activated aromatics such as phenol and aniline can be brominated to the tri-and tetrabrominated derivatives by using dilute aqueous solutions of bromine, whereas a controlled monobromination is very challenging and often requires cryogenic conditions. On the other hand, thermally controlled brominations of less activated aromatics such as toluene are rather slu ish reactions. Th often require photoinitiation and the use of Lewis adds as catalysts. 

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