Bromination with NBS

As we saw when discussing allylic bromination in Section 10.4, A-bromosuccin-imide (NBS) is a convenient free-radical brominating agent. Benzylic brominations with NBS are nonnally perfonned in carbon tetrachloride as the solvent in the presence of peroxides, which are added as initiators. As the exanple illustrates, free-radical bromination is selective for substitution of benzylic hydrogens. 

This allylic bromination with NBS is analogous to the alkane halogenation reaction discussed in the previous section and occurs by a radical chain reaction pathway. As in alkane halogenation, Br- radical abstracts an allylic hydrogen atom of the alkene, thereby forming an allylic radical plus HBr. This allylic radical then reacts with Br2 to yield the product and a Br- radical, which cycles back... 

Why does bromination with NBS occur exclusively at an allylic position rather than elsewhere in the molecule The answer, once again, is found by looking at bond dissociation energies to see the relative stabilities of various kinds of radicals. 

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. 

It is generally supported that the bromination with NBS proceeded by a radical (ref. 11) or an ionic mechanism via bromine molecule. For instance, the former was suggested in benzylic and allylic bromination with NBS for Whol-Ziegler reaction (ref. 12). Calo et al. (ref. 5) accounted NBS brominated phenol by the latter mechanism. 

The compounds 12,14 and 15 can be prepared from parent lysergic acid amides by bromination with NBS or PHT, but not the compounds of the type 12. The latter structure is very sensitive and under these circumstances only degradation products were obtained. Besides it was necessary to use much milder reagent, e.g. bromine bonded onto polymeric matrix with polyvinylpyrrolidone or polyvinylpyridine structure (29) ... 

The first stable derivative of methylene cyclopropene was the quinocyclopropene 108 reported in 1964 by Kende98 it was prepared from the cyclopropenium cation 106 which underwent pyrolysis and bromination with NBS to the p-hydroxy-phenyl substituted cation 107, which gave quinocyclopropene 108 by deprotonation ... 

The task of assaulting 72 was bestowed upon Chin Wing Chan whose undergraduate research work was under my direction. The key feature of our route to 72 doubtlessly revolved around the combined use of the Diels-Alder reaction in conjunction with low-valent-titanium deoxygenation. Thus, the known 75 was brominated with NBS to afford the dibromide 76, which was then dehydrobromi-nated in the usual way to give presumably the strained alkyne 77. As expected, all efforts to isolate 77 as a stable molecule were fruitless. However, 77 could be tr ped by furan to form the endoxide 78. Low-valent-titanium deoxygenation converted 78 to the desired molecule 72 (Scheme 16). ... 

Hydroxypyrazines or 2(l//)-pyrazinones are also subject to electrophilic halogenation. A new result is that 1-benzyl- or 1-phenyl-substituted 2(l//)-pyrazinones undergo bromination with NBS or A -iodosuccinimide (NIS) to give the 5-bromo or iodo-2(l//)-pyrazinones in 66-82% yields <2004TL1885, 2005T3953>. 

The ene-reaction, which is mechanistically related to the Diels-Alder reaction, has also been reported. The thermal addition of 3-ferf-butoxycarbonyl-2(3//)-oxazolone 236 to 2,2 -biindole 235 affords 4-(2,2 -biindol-3-yl)-2-oxazolidinone 237, probably via the indoline derivative. The product is further converted to the fused aromatic compound 238 by bromination with NBS and AIBN, followed by dehydrobromination (Fig. 5.58). ... 

Oxidation of dihydroisocoumarins is conveniently achieved through bromination with NBS followed by dehydrohalogenation with triethylamine (62JOC4337, 71T6171). Since the oxidation of isochromans to isochromanones proceeds readily using chromium trioxide, this method effectively constitutes a synthesis of isocoumarins from isochromans. 

Similarly, the silicon-substituted precursor 187 was obtained by the reaction of 184 and trimethylsilylacetylene in 88% yield (Scheme 23) <1999CPB1108>. The enyne 187 was hydroaluminated with DIBAL-H, followed by bromination with NBS to give (Z,Z)-dibromide 188 and its (Z,/. )-stcreoisomer 189 in a ratio 10 1 in ca. 60% yield. The dibromide 188 containing small amount of isomer 189 was treated with a excess of /-butyllithium, followed by (PhSC lzS resulting in ring closure to form the 2-trimethylsilyl-l-benzothiepine 29g in 26% yield, presumably via the 1,6-dilithium intermediate 190. 

The copolymer of ethylene withp-MS was available as a PE macroinitiator. PE-g-Br, which works as a PE macroinitiator for ATRP, was prepared from PE-g-MS by bromination with NBS [78], and PE-g-Br can be used to prepare PE-g-PMMA, PE-g-PS and PE-g-PnBA. 

Thus, 3-methylthiophene is brominated with NBS to give 2-bromo-3-methyl-thiophene (cf Figure 16) which is then metallated with n-butyllithium. The lithiated thiophene is activated with TMEDA and then coupled with 3,7,11-trimethyldodecanal. The coupled product contains a secondary alcohol which is... 

The synthesis of 23 was known to be amazingly simple pyruvic acid 22 is mixed with ammonia The yield is low, but who minds If you must have a low-yielding step, it is a good idea to have it at the start of the synthesis to avoid the waste of materials and energy. In this case, so much is achieved that a low yield is acceptable. Esterification gave the diester 21 R = Me which could be brominated with NBS (chapter 24) and combined with Ph P to give the phosphonium salt. This is the first branch complete. 

Radical bromination with NBS can result in the replacement of a sugar ring hydrogen by bromine.18 These reactions can be highly regioselective... 

Under free-radical conditions (e.g. in CC14) the cyclic tryptophan tautomer 15 undergoes bromination with NBS at the 3a-position, but under electrophilic conditions, aromatic bromination occurs at C-5 as reported by Crich and coworkers (equation 42)61. Their... 

Now the alkene is converted into an epoxide by a slightly unusual sequence. Bromination with NBS (N-bromosuccinimide) in water gives a mixture of bromohydrins by electrophilic addition to the... 

Radical bromination with fV-bromosuccinimide often succeeds. Thus, 2,5-disubstituted 4-methyloxazoles on bromina-tion give the 4-bromomethyl compounds, and methyl groups at the 4- or 5-positions of isoxazoles 568 and 569 can be brominated with NBS. Controlled mono- or dibromination of 3-aryl-5-methylisoxazole-4-carboxylates allows access to aldehydes <2004T2301>. 

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