Bromination by N-bromosuccinimide

Radecka and Nigam (17) have reported the direct titration of phenelzine with N-bromosuccinimide in acidic solution employing methyl red as the indicator. However, their results show a 5% positive bias. This bias is attributed to allylie bromination by N-bromosuccinimide. 

Stabilizing influences of substituents on free alkyl radicals. In brominations by N-bromosuccinimide a phenyl group has a greater stabilizing effect than a benzoyl or carboxyl group on the intermediate free radical.— E 4-Benzoyl-1-... 

EOTT, or, denoted by its lUPAC name, thieno-[3,4-i7]-l,4-oxathiane, is easily accessible via acid-catalyzed transetherification from 3,4-dimethoxy-thio-phene and 2-mercaptoethanol, as demonstrated by Blanchard, Roncali, and colleagues (Figure 13.12). A few derivatives were also described, demonstrating the chemical behavior of EOTT. Bromination by N-bromosuccinimide (NBS) results in a 85 15 isomer mixture of the two possible monobromination products (Figure 13.13). 

The isoxazole nucleus is also halogenated in the 4-position by N-bromosuccinimide provided there is no substituent in this position. This reaction does not proceed homolytically, as might have been expected, and appears to represent a simple electrophilic substitution by the bromine cation. Similar cases have been previously described for the bromination of certain aromatic compounds with A -bromo-succinimide. ... 

One such compound, bropirimine (112), is described as an agent which has both antineo-plastic and antiviral activity. The first step in the preparation involves formation of the dianion 108 from the half ester of malonic acid by treatment with butyllithium. Acylation of the anion with benzoyl chloride proceeds at the more nucleophilic carbon anion to give 109. This tricarbonyl compound decarboxylates on acidification to give the beta ketoester 110. Condensation with guanidine leads to the pyrimidone 111. Bromination with N-bromosuccinimide gives bropirimine (112) [24]. 

In a similar way, iV-bromination on the imidazole group of an imidazolide by N-bromosuccinimide increases the compound s reactivity E11],[140]... 

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. 

Protocol for Labeling Nucleic Acids by N-Bromosuccinimide Activation Bromination... 

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]. 

Saturated large rings may form nitrogen radicals by H abstraction from N, or abstraction may occur in the a- or (3-positions in non-nitrogen systems. Oxepane gives the radical in the 2-position, with subsequent cleavage and reclosure of the intermediate carbenoid to cyclohexanol (CHEC 5.17.2.1.5). In unsaturated large systems a variety of reactions, unexceptional in their nature, are found. Some azepines can be brominated by /V-bromosuccinimide others decompose under similar conditions (CHEC 5.16.3.7). 

Since the only by-product of the reaction is ethyl acetate, the silylated product can be employed for further reactions without purification. Examples include the fluoride-catalyzed aldol reaction14 and bromination with N-bromosuccinimide.10a... 

N-Iodosuccinimide reacts with enol acetates derived from ketones to give a-iodoketones, and the reaction has found application in the steroid field/ The iodination of the enol acetates seems to proceed by an ionic mechanism, and preliminary work indicates that N-iodosuccinimide is not capable of at least some of the radical-chain iodinations analogous to radical-chain brominations brought about by N-bromosuccinimide. ... 

Preparative Methods acid-catalyzed acetalization of Pivalalde-hyde with (l )-3-hydroxybutanoic acid gives the ci j-1,3-dioxan-4-one (2) in 40% yield after recrystallization from ether/pentane. (Up to 60% yield can be obtained by using freshly loaded acidic ion-exchange resin and following the procedure of Seebach et al. Runs with up to 120 g hydroxy butanoic acid were performed in this way). Bromination with N-Bromosuccinimide leads to a mixture of brominated dioxi-nones which are debrominated hydrogenolytically to (1) (eq 1). The yield (2) -> (1) is 45% after recrystallization from pen-tane/ether (50 3) at —20°C. The enantiomer ent- ) is of course equally readily available from (5)-3-hydroxybutanoic acid. Both enantiomers of 3-hydroxybutanoic acid are commercially available. 

Y(acac)3 can be brominated with N-bromosuccinimide at carbon-3 forming Y(3-Bracac)3, isolated as a monohydrate. NMR spectroscopy shows that in solution two rings chelate via O and Br, the other by two oxygens the molecule is fluxional." " ... 

An attempt has been made to synthesize the morphinane ring-system in this way, and l-(/3-diethylaminoethyl)-2-keto-1 2 3 4-tetrahydro-naphthalene was converted to [oxxvm] by condensation with the appropriate Mannich base methiodide, the product brominated with N-bromosuccinimide, and finally converted to the quaternary salt [cxxix]. Work on the corresponding N-dimethyl series was abandoned when it was found impossible to obtain the requisite substituted /3-tetralone in a state even approaching purity. The synthesis of [cxxx] has been accomplished by the same method, its production being accompanied by the production of [cxxxi] as a result of further ring-extension [43]. 

Dihydro-l//-2,l,3-benzothiadiazine 2,2-dioxide (46) has been oxidized to 3//-2,l,3-benzothiadiazine 2,2-dioxide (47) with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (Scheme 6). The oxidation may also be carried out by irradiating a solution of the dihydro compound while adding bromine. With N-bromosuccinimide (NBS), and if substituents are not present in the 6- or 8-position, bromination occurs prior to oxidation (79JHC1069). 

Recently, Nakamura et al. successfully synthesized a regioisomer of kealiiquinone (Scheme 11) [50]. l-Methyl-2-phenylthio-lff-imidazole 44 was first converted into the 5-substituted imidazole 45, then the benzylic hydroxyl group in 45 was protected by a ferf-butyldimethylsilyl (TBDMS) group, and bromination with N-bromosuccinimide gave the bromide 46. Lithiation by ferf-butyllithium at the 4-position of 46 followed by trapping with 3,4-dimethoxy-2-(methoxymethoxy)benzaldehyde gave the tetrasubstituted imidazole 47 as a diastereomeric mixture. Acetylation of the hydroxy group of 47... 

Electrophilic substitutions of thiazolo[2,3-/]purinediones were demonstrated by the reaction of l,3-dimethyl-6-phenylthiazolo[2,3-/]purine-2,4(177,377)-dione (121) with bromine or N-bromosuccinimide producing the 7-bromo derivative 123. 

Oxidation of cyclic tertiary amines with hydrogen atoms a to the nitrogen, by bromine or N-bromosuccinimide under basic conditions, has been investigated. Experimental conditions for lactam formation were precisely defined. 21-Nor-conanine (17) and 20-methylconanine (18) with one mole of bromine (or NBS) in the... 

A route to canthaxanthin using Wittig reaction methodology has been described (ref. 50). In this approach retinol (vitamin A) was oxidised in dichloromethane with manganese dioxide to retinal (vitamin A aldehyde) which was converted to 4-acetoxyretinal by bromination with N-bromosuccinimide in dichloromethane containing acetic acid. By reaction with retinyltriphenylphosphonium hydrogensulphate derived by reaction of triphenylphosphine with retinol hydrogensulphate, isocryptoxanthin acetate was obtained. Treatment of this with 68% hydrobromic acid formed... 

Naphthoquinones have been generated by a non-oxidative route involving bromination with N-bromosuccinimide in the 1-position of the respective 2-keto tautomer as the mono t-butyidimethylsilyl derivative, treatment of the bromo compound with tetra-n-butylammonium fluoride and trapping of the product as a norbornadiene adduct, in a yield of 64% in the case of the 1,4-diphenyl member (ref.58). 

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