Dibromine

Dibromine monoxide, BtjO, is prepared, similar to the corresponding dichlorine compound, by the action of a solution of bromine in carbon tetrachloride on yellow mercury(II) oxide ... 

Similarly o-sulphobeiizoic anhydride and o-cresol yields o-cresolsulphone-phthalein (o-cresol red) dibromination of the last-named gives dibromo-o-sulphonephthaleln (bromocresol purple) ... 

Epoxide opening with nucleophiles occurs at the less substituted carbon atom of the oxlrane ting. Cataiytic hydrogenolysis yields the more substituted alcohol. The scheme below contains also an example for trons-dibromination of a C—C double bond followed by dehy-drobromination with strong base for overall conversion into a conjugated diene. The bicycKc tetraene then isomerizes spontaneously to the aromatic l,6-oxido[l0]annulene (E. Vogel, 1964). 

Orotic acid undergoes 5-nitration, 5-bromination in hydrobromic acid with peroxide, 5,5-dibromination following decarboxylation in bromine water, esterification, methylation (rather complicated), conversion into its acid chloride (containing some anhydride) by treatment with thionyl chloride, and conversion into 2,6-dichloropyrimidine-4-carboxylic acid by phosphoryl chloride (62HC(16)422). 

Recent gas chromatographic analysis showed that about 9% of 2,3-dibromo-and 2% of 2,4-dibromothiophene is formed in the dibromination of thiophene. Sice, J. Am. Chem. Soc. 75, 3697 (1953). 

Bromine in pyridine largely dibrominated 2-amino- and 2-hydroxy-1,3-diazulenes (35), although some mono- and tri-bromo products were also detected (88BCJ2690). 

Reactions in acetic anhydride with metal acetates present probably occur by 1,4-addition of bromonium acetate (85CHE458). When NBS in sulfuric acid at 20°C was used, the product ratio resembled that observed with bromine-sulfuric acid-silver sulfate. At 60°C the ratio changed to 2 1.2 1 as a consequence of more extensive dibromination (88CHE892) (Scheme 33). As might have been deduced, 2-(2 -thienyl)quinoline was brominated only in the thiophene ring (82CHE28). 

Vapor phase brominations have given rise to varying products dependent on the reaction temperature. At 300°C bromine converted quinoline in the presence of pumice into 68 (25%) at 450°C 2-bromoquinoline (25%) became the major product at 500°C the yield of the 2-bromo isomer increased to 53%, but there was some dibrominated material [77HC(32-1)319]. The absence of 3-bromoquinoline at the higher temperatures could be accounted for in terms of radical attack, or it could be due to thermal instability of that isomer [59CI(L)1449]. 

If a slight excess of bromine has been added, a light yellow color remains after reaction of one equivalent since dibromination is very slow under these conditions. 

This procedure, in contrast to previous methods, comprises only one step and is readily adapted to large-scale preparative work. Furthermore dibromination is very slow in methanol and hence the crude reaction products contain only traces of dibromo ketones. This contrasts with the behavior in other solvents such as ether or carbon tetrachloride, where larger amounts of dibromo ketones are always present, even when one equivalent of bromine is used. Methanol is thus recommended as a brominating solvent even when no orientation problem is involved. It should be noted that a-bromomethyl ketals are formed along with x-bromoketones and must be hydrolyzed during the workup (Note 8).7... 

Brick et al. have studied this bromination in more detail and showed that the extent of the bromination can be controlled by changing the ratio of the reagents. The first substitution was found to be in the para position but subsequent intramolecular rearrangements allowed the formation of 2-5-dibrominated species. Brick et al. also reported the functionalization of such species using Pd-catalyzed reactions such as Heck and Suzuki couplings to give fully substituted p-stilbenes, p-biphenyls, diarylamines, and methylcinnamates. Hydrogenation of... 

Several methods for direct o/t/to-bromination and < /t/to-dibromination of phenols have been reported (refs. 4,5). Pearson et al. (ref. 6) found that treatment of phenols with bromine in the presence of a large excess of f-butylamine at - 70°C gave 2-bromo- or 2,6-dibromophenols in good yields. Recently, Schmitz et al. (ref. 7) showed that the reaction between phenol and AT,A -dibromomethylamine efficiently affords 2,6-dibromophenol. 

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. 

We considered A-bromoamines which generated in situ from the reaction of NBS and various amines, should promote the o/t/io-dibromination of phenol. The results of the bromination with NBS in the presence of amines are summarized in Table 2. 

Table 2. Dibromination of Phenol with NBS in the Presence of Primary, Secondary, and Tertiary Amines )...

Addition of every primary amine was effective for obtaining the ortho-dibromide selectively. In the absence of amines, the yield of 2,6-dibromophenol was much lower than that of 2,4,6-tribromophenol. The selective ortho-dibromination of phenols was also observed when secondary amines were added. 

The mechanism of the orf/to-dibromination of phenol with NBS in the presence of amines is considered as follows. The hydrogen bonding between phenol and N-bromoamine which are generated from the reaction of NBS and amines (ref. 14), is the driving force, and causes the bromination at one o/t/io-position of phenol and regeneration of the amines. A catalytic amount of the amines is enough because of the regeneration of the amines. The repetition of the above process causes one more substitution at the other orf/io-position of 2-bromophenol. In the cases of 2-substituted phenols the orf/io-bromination can occur only once (Scheme 5). 

This reaction has been also described for low chlorinated dibenzodioxins. Assuming an identical MS response factor for monoBrDD and monobromohydroxy-biphenyl ether (monoBrDPE) a quantification study shows that monoBrDPE is much more stable towards photolysis compared to monoBrDD, because it accumulates in the mixture of the reaction products. For the dibrominated dibenzodioxins the same reaction (ether fission) is observed but to a minor extent. With triBrDD and higher brominated BrDD no diaryl-ether products are observed at all. 

Ingenious experiments to which reference has already been made have used addition of specific PCB congeners that are more readily dechlorinated to prime dechlorination at specific positions (Bedard and Quensen 1995). They have been extended to the use of dibrominated biphenyls in the presence of malate to stimulate dechlorination of the hexachloro- to nanochlorobiphenyls (Bedard and Quensen 1995). Results from these experiments provide valuable evidence of important differences between anaerobic dechlorination and anaerobic debromination, and the greater facility of the latter. 

Whilst for the analysis of plant material for cannabinoids both GC and HPLC are commonly used, in analytical procedures the employment of GC-based methods prevails for human forensic samples. Nonetheless, the usage of HPLC becomes more and more of interest in this field especially in combination with MS [115-120]. Besides the usage of deuterated samples as internal standards Fisher et al. [121] describe the use of a dibrominated THC-COOH (see 7.5). The usage of Thermospray-MS and electrochemical detection provide good performance and can replace the still-used conventional UV detector. Another advantage in the employment of HPLC rather than GC could be the integration of SPE cartridges, which are needed for sample preparation in the HPLC-system. 

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