Bromination benzylic, bromosuccinimide

Either elemental bromine (much cheaper) or A-bromosuccinimide may be used as the reagent for benzylic bromination. (V-Bromosuccinimide is preferred for allylic bromination (Section 15-7) because Br2 can add to the double bond. This is not a problem with the relatively unreactive benzene ring unless it has powerful activating substituents. 

Halogenation (Section 11 12) Free radical halo genation of alkylbenzenes is highly selective for substitution at the benzylic position In the exam pie shown elemental bromine was used Alterna Lively N bromosuccinimide is a convenient re agent for benzylic bromination... 

Treatment of pyrrole, 1-methyl-, 1-benzyl- and 1-phenyl-pyrrole with one mole of A -bromosuccinimide in THF results in the regiospecific formation of 2-bromopyrroles. Chlorination with IV-chlorosuccinimide is less selective (8UOC2221). Bromination of pyrrole with bromine in acetic acid gives 2,3,4,5-tetrabromopyrrole and iodination with iodine in aqueous potassium iodide yields the corresponding tetraiodo compound. 

Allylicor benzylic bromination or chlonnalion with N bromosuccinimide (NBS) or NCS... 

A -Bromosuccinimide has been used in combination with benzyl alcohol for the bromination of ketones ... 

As mentioned in an earlier section (cf. Chapter 1, Section III), allylic positions are subject to attack by free radicals resulting in the formation of stable allyl radicals. A-Bromosuccinimide (NBS) in the presence of free-radical initiators liberates bromine radicals and initiates a chain reaction bromination sequence by the abstraction of allylic or benzylic hydrogens. Since NBS is also conveniently handled, and since it is unreactive toward a variety of other functional groups, it is usually the reagent of choice for allylic or benzylic brominations (7). 

Side-chain bromination at the benzylic position occurs when an alkylbenzene is treated with /V-bromosuccinimide (NBS). For example, propylbenzene gives (l-bromopropyl)benzene in 97% yield on reaction tvith NBS in the presence of benzoyl peroxide, (PhC02)2f as a radical initiator. Bromination occurs exclusively in the benzylic position and does not give a mixture of products. 

The benzylic position of an alkylbcnzene can be brominated by reaction with jV-bromosuccinimide, and the entire side chain can be degraded to a carboxyl group by oxidation with aqueous KMnCfy Although aromatic rings are less reactive than isolated alkene double bonds, they can be reduced to cyclohexanes by hydrogenation over a platinum or rhodium catalyst. In addition, aryl alkyl ketones are reduced to alkylbenzenes by hydrogenation over a platinum catalyst. 

Al-Bromosuccinimide is also a highly regioselective brominating agent at other positions, including positions a to a carbonyl group, to a C=C triple bond, and to an aromatic ring (benzylic position). When both a double and a triple bond are in the same molecule, the preferred position is a to the triple bond. ... 

The accessibility of ethyl-substituted stabilizer precursors suggests benzylic bromination with N-bromosuccinimide followed by base-catalyzed dehydrobromination. Tertiary amines were found to be particularly effective in the syntheses described in this paper. 

Et3N-3HF as a fluorinating agent [285, 286] or with other reagents [475, 476], Benzylic brominations with N-bromosuccinimide in the presence of a radical initiator have been investigated by van Koten [287]. 

N-Bromosuccinimide in bromination of o-nitrotoluene to form u-nitro-benzyl bromide, 46, 81 -Bromotoluene, conversion to Grignard reagent, 47,108... 

Direct bromination of toluene and ethylbenzene form the corresponding benzyl bromides in high yield. The observed selectivity in SC-CO2 is similar to that observed in conventional organic solvents. Also, SC-CO2 is an effective alternative to carbon tetrachloride for use in the classical Ziegler bromination with N-bromosuccinimide. Reaction yields are high, side products are minimized, and bromine-atom selectivities are observed. Thus, SC-CO2 must be useful as a viable, environmentally benign substitute for many of the solvents typically used for free-radical reactions (Tanko and Blackert, 1994). 

A typical procedure is that described in Expt 6.119 for the synthesis of 1-naphthaldehyde. The synthesis of p-nitrobenzaldehyde provides an example in which the intermediate crystalline hexamine salt is isolated prior to hydrolysis. 2-Naphthaldehyde is prepared from the bromomethyl compound, the preparation of which illustrates the use of Af-bromosuccinimide for effecting benzylic bromination of 2-methylnaphthalene. 

Table 4-1 compares two different reactions, namely, anode oxidation and oxidation with cerium ammonium nitrate (which are bona fide electron-transfer processes) and bromination by /V-bromosuccinimide in the presence of azobis(iso-butyro)nitrile (which is bona fide hydrogen-atom-transfer process). Both electron-transfer and hydrogen-atom-transfer processes have the benzylic radical as a common intermediate, but positional selectivity is stronger for electron-transfer processes. Another important point is the preference of the 2-positioned methyl group over the 1-positioned group, in terms of selectivity. For 1,2,3-tetramethylbenzene, such a preference reaches values from 16 to 55, and it is over 200 for 5-methoxy-1,2,3-tctramcthylbcnzcnc. 

Only benzylic (or ally lie) hydrogens are replaced by A-bromosuccinimide. Among the four bromines in 3,4,5-tribromobenzyl bromide, three are substituents on the ring and are not capable of being introduced by benzylic bromination. The starting material must therefore have these three bromines already in place. 

Direct introduction of a vinyl substituent onto an aromatic ring is not a feasible reaction. p-Methoxystyrene must be prepared in an indirect way by adding an ethyl side chain and then taking advantage of the reactivity of the benzylic position by bromination (e.g., with N-bromosuccinimide) and dehydrohalogenation. 

The sequence that presents itself begins with benzylic bromination with N-bromosuccinimide. 

V-Bromosuccinimide (NBS) is a reagent used to substitute benzylic and allylic hydrogens with bromine. The benzylic bromide undergoes SN2 substitution with the nucleophile, methanethiolate. As in part (e), the alkyl halide is more reactive toward substitution than the aryl halide. 

An efficient procedure for the formation of primary bromides is the reaction of 4,6-O-benzylidene hexopyranosides with A-bromosuccinimide (NBS) in the presence of barium carbonate. This reaction leads to the corresponding 4-0-benzoyl-6-bromide-6-deoxy-glycoside (Scheme 3.4a).17 Probably, the reaction proceeds by the radical bromination of the benzylic carbon atom followed by rearrangement to the 6-deoxy-6-bromo derivative. The application of this method is very efficient since the benzylidene functionality can act as a protecting group but can be oxidatively cleaved to give a 6-deoxy-6-bromo derivative. 

Hydrogen atoms in the benzylic position can be replaced by elemental bromine as shown. This is not true for hydrogen atoms in the allylic position. The alkene reacts rapidly with molecular bromine via addition and allylic bromination is not observed (Figure 1.25, left). A chemoselective allylic bromination of alkenes succeeds only according to the Wohl-Ziegler process (Figure 1.25, right), that is, with A-bromosuccinimide (NBS). 

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