Bromination usefulness

Bromine water, saturated solution to 400 mL water add 20 mL of bromine use a glass stopper coated with petrolatum. 

Halogenation. Succinic acid and succinic anhydride react with halogens through the active methylene groups. Succinic acid heated in a closed vessel at 100°C with bromine yields 2,3-dibromosuccinic acid almost quantitatively. The yield is reduced in the presence of excess water as a result of the formation of brominated hydrocarbons. The anhydride gives the mono- or dibromo derivative, depending on the equivalents of bromine used. 

Phenols and phenol ethers readily undergo mono-, di-, or trihromination in inert solvents depending on the amount of bromine used. In water the main product is the 2,4,6-tribromophenol [118-79-6] C H Br O (23). In water or acetic acid anilines also give the tribrorninated product (25). 

Typical specifications for bromine produced ia a modem plant (54) generally exceed the ACS requirements for bromine used as a reagent chemical (55) (Table 4). 

Bromination using NBS has been used to provide acetylpyrazine derivatives from the corresponding ethylpyrazines. Bromination of 2-ethyl-3-methylpyrazine gives 2-bromoethyl-3-methylpyrazine in quantitative yield this may be oxidized using the sodium salt of 2-nitropropane or with pyridine AT-oxide to yield 2-acetyl-3-methylpyrazine in yields of 66 and 25% respectively (Scheme 14). 

X-RAY FLUORESCENCE ANALYSIS OE ORGANIC COMPOUNDS CONTAINING BROMINE USING QUASI-SOLID SPECIMENS... 

Nitrosyl bromide (NOBr) decomposes to nitrogen oxide and bromine. Use the following data to determine the order of the decomposition reaction of nitrosyl bromide. 

Bradfield et al.21g first studied the kinetics of molecular bromination using aromatic ethers in 50% aqueous acetic acid at 18 °C. They showed that the kinetics are complicated by the hydrogen bromide produced in the reaction which reacts with free bromine to give the tribromide in BrJ, a very unreactive electrophile. To avoid this complication, reactions were carried out in the presence of 5-10 molar excess of hydrogen bromide, and under these conditions second-order rate coefficients (believed to be I02k2 by comparison with later data) were obtained as follows after making allowance for the equilibrium Br2 + Br7 Bn, for which K = 50 at 18 °C 4-chloroanisole (1.12), 4-bromoanisole (1.20), 4-... 

Monobromination with bromine leads to exclusive 4-bromophenol, and dibromination with the same reagent gave predominant 2,4-dibromophenol. In the case of monobromination with NBS, the main product was 2-bromophenol, but no selectivity appeared in the bromination using two molar amounts of NBS. 

As described above, it was shown that A,iV-dibromomethylamine was effective for orr/io-dibromination of phenol (ref. 7). We also carried out a bromination using NBB as A-bromoamine analogue. One molar amount of NBB did not give 2-bromophenol selectively, but gave a mixture of o/t/io-monobromophenol and 2,6-dibromophenol, and a considerable amount of phenol was recovered. On the other hand, 2,6-dibromophenol was obtained in an 81.7 % yield when two molar amounts of NBB were used. These results suggested that 7V-bromoamines were the best reagents for orf/io-bromination of phenol. However N-bromoamines were very unstable and decomposed explosively in less than a day at room temperature. 

Whilst this process is attractive in that it removes an effluent problem and fully utilises the bromine used, it must be recognised that for some reactions, particularly where there is a degree of water sensitivity, the approach will not be practicable. 

In terms of economics, it has been calculated that the capital cost requirement for a unit to recover bromine by this method is relatively low. Consideration of the operating costs shows that the cost of recovered bromine using this process is about 30 % of that for purchasing new bromine. This takes no account of the savings associated with not having to dispose of the bromide. 

The Knoovenagol method (p T 161 ) gives high yields of crotonic acid. The allylic bromination uses N3S in CCl and the ylid (9) is stable enough to be isolated. 

The major disadvantage with bromination is the extreme toxicity of bromine. Use a fume hood for all operations. Avoid the breathing of fumes or contact with skin or eyes. Protective clothing and gloves are recommended. 

Most brominations used for synthetic purposes are carried out in halogenated solvents. There are, however, only a few mechanistic studies in these media, since it was difficult to obtain reproducible rate constants. Even now that reliable procedures have been published (Schmid et ai, 1972 Bellucci et ai, 1981), the upper limit of the rate constants available is about 10s—106 m-2 s-1, since only spectroscopic techniques can be used. 

Ground-glass equipment is preferred corks are attacked by the bromine used later. 

Cyclobutane-1,2-dione, bromine used in formation of, 4 303 Cyclobutane derivatives, 75 489 Cyclobutene adducts, 75 489... 

Lewis acid catalyst is normally required when ammonium polyhalides are used, although recourse does not have to be made to strong acids, such as aluminium trichloride. Bromination and iodination reactions are normally conducted in acetic acid in the presence of zinc chloride [32], but chlorination using the ammonium tetrachloroiodate in acetic acid does not require the additional presence of a Lewis acid [33]. Radical chlorination of toluenes by benzyltrimethylammonium tetrachloroiodate in the presence of AIBN gives mixtures of the mono-and dichloromethylbenzenes [34], Photo-catalysed side-chain chlorination is less successful [35], Radical bromination using the tribromide with AIBN or benzoyl peroxide has also been reported [36, 37],... 

Radical-initiated allylic bromination using NBS, and catalytic AIBN as initiator or NBS under photolysis. 

In 1842 Balard succeeded Thenard at the Sorbonne, and in 1851 he accepted a professorship at the College de France (36). He discovered hypochlorous acid, worked out the constitution of Javelle water (44), and perfected industrial methods for the extraction of various salts from sea water. He worked for twenty years at these technical researches, and extracted sodium sulfate, the basis of the soda industry, directly from sea water. He also extracted potassium salts from the sea water, and his artificial potash, entering into competition with that from the ashes of plants, soon lowered the price. Before the discovery of the Stassfurt deposits in 1858, all the bromine used by photographers was prepared by Balard s method. 

Very recently, Hu et al. claimed to have discovered a convenient procedure for the aerobic oxidation of primary and secondary alcohols utilizing a TEMPO based catalyst system free of any transition metal co-catalyst (21). These authors employed a mixture of TEMPO (1 mol%), sodium nitrite (4-8 mol%) and bromine (4 mol%) as an active catalyst system. The oxidation took place at temperatures between 80-100 °C and at air pressure of 4 bars. However, this process was only successful with activated alcohols. With benzyl alcohol, quantitative conversion to benzaldehyde was achieved after a 1-2 hour reaction. With non-activated aliphatic alcohols (such as 1-octanol) or cyclic alcohols (cyclohexanol), the air pressure needed to be raised to 9 bar and a 4-5 hour of reaction was necessary to reach complete conversion. Unfortunately, this new oxidation procedure also depends on the use of dichloromethane as a solvent. In addition, the elemental bromine used as a cocatalyst is rather difficult to handle on a technical scale because of its high vapor pressure, toxicity and severe corrosion problems. Other disadvantages of this system are the rather low substrate concentration in the solvent and the observed formation of bromination by-products. 

The initially patented synthesis of cetirizine (4) by UBC S. A. in Belgium was an extension of the hydroxyzine (41) synthesis.Gngnard addition to p-chlorobenzaldehyde gave (4-chloro-phenyl)-phenyl-methanol, which was easily brominated using PBrs in benzene to give 4-chlorodiphenylmethyl bromide (42). Sn2... 

In the synthesis of zafirlukast (5), as shown in Scheme 14.13, 40 was brominated using DBDMH/AIBN to afford 41. Subsequently, the indole and sulfonamide moieties were combined to achieve the synthesis of 5. 

Table 1. Substitution of Chlorine or Bromine Using Hydrogen Fluoride with Aluminum Trifluoride Catalysis...

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