Ortho -Bromophenol

Various bromophenols are useful precursors for medicinal drugs, agricultural chemicals, dyes, and flame retardants. It is difficult to synthesize directly ortho-bromophenols by use of bromine with which bromination afford para-substitution predominantly (ref. 1). Thus desired ort/io-bromophenols were generally prepared via tedious steps as shown in Scheme 1 (refs. 2,3). 

The investigation on the influence of the temperature on the hydrolysis rate of the ortho-bromophenol into the catecholate shows that the induction time depends strongly on the temperature from about 5 hours at 135°C to 1 hour at 165°C and 1/2 hour at 180°C (Fig. 17). 

The shifts are smallest in the ortho and para positions so these are where there is greatest electron density and hence these are the sites for electrophilic attack. The shifts in the meta positions are not significantly different from those in benzene. If you want to put just one bromine atom into a phenol, you must work at low temperature (< 5°C) and use just one equivalent of bromine. The best solvent is the rather dangerously inflammable carbon disulfide (CS2), the sulfur analogue of C02. Under these conditions, para bromophenol is formed in good yield as the main product, which is why we started the bromination of phenol in the para position. The minor product is ortho bromophenol. 

When phenol is treated with Br2, a mixture of monobromo-, dibromo-, and tribromophe-nols is obtained. Design a synthesis that would convert phenol primarily to ortho-bromophenol. 

Halophenols without 2,6-disubstitution do not polymerize under oxidative displacement conditions. Oxidative side reactions at the ortho position may consume the initiator or intermpt the propagation step of the chain process. To prepare poly(phenylene oxide)s from unsubstituted 4-halophenols, it is necessary to employ the more drastic conditions of the Ullmaim ether synthesis. A cuprous chloride—pyridine complex in 1,4-dimethoxybenzene at 200°C converts the sodium salt of 4-bromophenol to poly(phenylene oxide) (1) ... 

A spore-forming strain of Desulfitobacterium chlororespirans was able to couple the dechlorination of 3-chloro-4-hydroxybenzoate to the oxidation of lactate to acetate, pyruvate, or formate (Sanford et al. 1996). Whereas 2,4,6-trichlorophenol and 2,4,6-tribro-mophenol supported growth with the production of 4-chlorophenol and 4-bromophenol, neither 2-bromophenol nor 2-iodophenol was able to do so. The membrane-bound dehalogenase contains cobalamin, iron, and acid-labile sulfur, and is apparently specific for ortho-substituted phenols (Krasotkina et al. 2001). 

The robust nature of the rhodium-iodide catalyst is also revealed in reactions with ortho-halo phenols that proved to be problematic with the first-generation catalyst system (Section 9.3.1). By employing the [Rh(PPF-P Bu2)I] catalyst, complete conversion is obtained with 2-bromophenol to give 6 in 94% yield, and with 95% enantiomeric excess after only 1.5 h of reaction time at 1 mol% catalyst loading (Scheme 9.3) [11]. The ready availability of these ring-opened compounds has been utilized to prepare enan-tiomerically enriched benzofurans 7. 

Phenols undergo electrophilic substitutions. In phenol, the substitutions take place in ortho and para positions. As the —OH group is an activating group, the reaction rate is much faster than usually observed with benzene. For example, the bromination of phenol produces ort/io-bromophenol (12%) and para-bromophenol (88%). 

Chloro- and bromophenols and A -acylhaloanilines can be fluorinated in the ortho or para position by 1-fluoropyridinium triflates and the fluorophenols and iV-acylfluorohaloanilines thus obtained reduced to fluorophenols and iV-acylfluoroanilincs. For example, 4-chlorophenol reacts with 2-chloro-l-fluoro-6-(trichloromethyl)pyridinium tetrafluoroborate in 1,2-dichlo-roethane at 45°C for three hours to give 4-chloro-2-fluorophenol in 68% yield.51... 

In a two-phase system similar to that used by Price, Stamatoff (29) obtained from 2,6-dichloro-4-bromophenol a branched polymer having approximately the statistical ratio of ortho and para ether linkages. When the reaction was carried out using the anhydrous salt of the phenol in the presence of highly polar aprotic solvents, such as dimethyl sulfoxide, the product was the linear poly(2,6-dichlorophenylene oxide) (Reaction 23). 

At a temperature of 78° C. the velocity constant whether referred to a unimolecular or a bimolecular reaction diminished with time after an hour rather less than three-quarters of the original metaphosphate remains.6 The product is mainly orthophosphate, as was proved by titration with methyl orange and phenolphthalein, although small quantities of pyrophosphate were formed by a side reaction. The pyro-acid was determined by titration to bromophenol blue in the presence of zinc sulphate, which leads to a complete precipitation of pyrophosphate, the ortho-acid being unaffected, thus... 

The position of a trimethylsilyl substituent in phenols 33 determines great yield differences in both thiocarbamate formation and rearrangement [57, 58]. The required TMS-substituted phenols, which were prepared from the respective bromophenols, were tested under standard conditions (Scheme 19). The yield of the rearrangement decreased as the substituent moved from para to ortho. 

A number of the reactions of phenols are typical of ends. Thus they are readily halogenated in the ortho and para positions, with a marked tendency for polyhalogenation. Bromination of phenol with bromine in carbon tetrachloride gives 4-bromophenol, but 2,4,6-tribromophenol is formed with bromine water. 

IUPAC Nomenclature of Phenols Section 9.1C (a) 2-methylphenol (b) 3-bromophenol (c) 4-ethylphenol (ortho, meta, and para in a,b,c respectively is correct also) d) 4-methoxy-2-nitrophenol... 

Pearson27 was to manipulate orientation in various ways to obtain any isomer desired. An example cited on 1, 32-33 is the meru-bromination of acetophenone, described by Pearson as a swamping catalyst effect. In the bromination of a phenol, para substitution ordinarily predominates over ortho substitution, but considerable increase in the proportion of ortho isomer can be achieved by operating at — 70° in the presence of a strongly basic aliphatic amine.28 The best procedure was to add bromine to a cold solution of f-butylamine in toluene, cool to about — 7(P, and add a phenol dropwise over a short period of time. By this procedure, phenol was converted by 1 equivalent of bromine into 2-bromophenol in 60% yield and by 2 equivalents of bromine into 2,6-dibromophenol in 87% yield. Tertiary amines such as DABCO and triethylamine serve also for enhanced o-bromination of phenols. Chlorination under the same conditions gave a mixture of o- and p-chlorophenols in the ratio 2 1. 

While using o-bromophenol as the ort/w-arylating agent in the above sequence, Catellani found the product to be a 67/-dibenzopyran, the product of an ortho-arylation/Mizoroki-Heck coupling followed by an oxy-Michael addition of the phenol to the electron-deficient alkene. This was later developed into an efficient method for the synthesis of a variety of 6//-dibenzopyrans (Scheme 21) [56, 57], and is one of the most modular and effective methods to construct this interesting heterocyclic framework. 

Bromophenol. The unexpanded spectrum shows two doublets and two triplets, consistent with a 1,2-disubstituted ortho) pattern. Each shows fine structure in the expansions Assignments can be made by assuming that the two upheld protons (shielded) are ortho and para with respect to the electron-releasing OH group. The other two patterns can be assigned by a process of elimination. 

In the second stage, the bromination, the OH directs to the ortho and para positions, but only one ortho position is vacant, so the bromine attacks there. Sodium hydroxide is needed to deprotonate the sulfonic acid groups to make them less deactivating. The sulfonation reaction is reversible, and in the third stage it is possible to drive the reaction over to the products by distilling out the relatively volatile 2-bromophenol at high temperature. The loss of SO3 involves attack of H on the aromatic ring. 

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