A/-bromosuccinimide

Alternative Names NBS l-bromo-2,5-pyrrolidinedione. Physical Data mp 173-175 °C (dec) d 2.098 gcm . Solubility sol acetone, THF, DMF, DMSO, MeCN slightly sol H2O, AcOFI insol ether, hexane, CCI4 (at 25 °C). 

Form Supplied in white powder or crystals having a faint odor of bromine when pure widely available. 

Purification in many applications the use of unrecrystallized material has led to erratic results. Material stored for extended periods often contains significant amounts of molecular bromine and is easily purified by recrystallization from H2O (AcOFI has also been used). In an efficient fume hood (caution bromine evolution), an impure sample of NBS (200 g) is dissolved as quickly as possible in 2.5 L of preheated water at 90-95 °C. As filtration is usually unnecessary, the solution is then chilled well in an ice hath to effect crystallization. After most of the aqueous portion has been decanted, the white crystals are collected by filtration through a bed of ice and washed well with water. The crystals are dried on the filter and then in vacuo. The purity of NBS may be determined by the standard iodide-thiosulfate titration method. 

Introduction. IV-Bromosuccinimide is a convenient source of bromine for both radical substitution and electrophilic addition reactions. For radical substitution reactions, NBS has several advantages over the use of molecular Bromine, while l,3-Dibromo-5,5-dimethylhydantoin is another reagent of use. N-Chlorosuccinimide and N-Iodosuccinimide generally do not 

Essential Reactions for Organic Synthesis, First Edition. Edited by Philip L. Fuchs. 2016 John Wiley Sons, Lid. Published 2016 by John Wiley Sons, Ltd. 

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A -Bromosuccinimide (prepared by the action of bromine on succinimide at o in the presence of sodium hydroxide) is a valuable specific reagent for brominating olefines in the a-methylene position to the double bond without simultaneously adding bromine to this bond. For example, if A -bromosuccini-mide is represented by (C4H40t)NBr —... 

The substitution is best carried out by boiling A -bromosuccinimide with the olefine in carbon tetrachloride. Succinimide crystallises out from the carbon tetrachloride on cooling w hereas the brominated product remains dissolved in the carbon tetrachloride. 

Strecker Degradation (Oxidative Deamination), Mild oxidizing agents such as aqueous sodium hypochlorite or aqueous A-bromosuccinimide, cause decarboxylation and concurrent deamination of amino acids to give aldehydes. 

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. 

Treatment of a carborane derivative of thiirane with A-bromosuccinimide gives a j3-bromodisulfide (79MI50601). Chlorination of CM-2,3-di-f-butylthiirane by f-butyl hypochlorite proceeded differently to the reaction with chlorine itself (Scheme 41) (74JA3146). 

Tropolone has been made from 1,2-cycloheptanedione by bromination and reduction, and by reaction with A -bromosuccinimide from cyolo-heptanone by bromination, hydrolysis, and reduction from diethyl pimelate by acyloin condensation and bromination from cyclo-heptatriene by permanganate oxidation from 3,5-dihydroxybenzoic acid by a multistep synthesis from 2,3-dimethoxybenzoic acid by a multistep synthesis from tropone by chlorination and hydrolysis, by amination with hydrazine and hydrolysis, or by photooxidation followed by reduction with thiourea from cyclopentadiene and tetra-fluoroethylene and from cyclopentadiene and dichloroketene. - ... 

Bromination with A-bromosuccinimide generally gives the same result as bromination with free bromine or hypobromous acid. The reaction is considered to proceed with a small concentration of free bromine and does not generate an appreciable concentration of acid. Conditions are therefore mild. In addition, A-bromosuccinimide has been used to brominate the allylic position of a, -unsaturated ketones in the presence of free-radical promoters or with irradiation, and thus gives access to dienones by dehydro-halogenation, for exaraple " ... 

The reaction of A -bromosuccinimide with 5a-cholestan-3-one enol acetate in aprotic conditions, described by Green and Long, is probably free radical in character cf. ref. 69). 

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

In analogy with the peracid attack on steroidal double bonds, the formation of the bromonium ion, e.g., (81a), occurs from the less hindered side (usually the a-side of the steroid nucleus) to give in the case of the olefin (81) the 9a-bromo-l l -ol (82). Base treatment of (82) provides the 9 5,1 l S-oxide (83). Similarly, reaction of 17/3-hydroxyestr-5(10)-en-3-one (9) with A -bromosuccinimide-perchloric acid followed by treatment with sodium hydroxide and sodium borohydride furnishes the 3, 17 5-dihydroxy-5a,l0a-oxirane. As mentioned previously, epoxidation of (9) with MPA gives the 5, 10 -oxirane. °... 

The method of Fried and Sabo for the in situ preparation of hypobromous acid from A-bromoacetamide (or A-bromosuccinimide) in aqueous dioxane or acetone containing perchloric acid is commonly used, e.g., (81) (82). 

The elements of bromine azide have been added to steroid olefins. The addition can be rationalized as proceeding through a positive bromonium ion under the ionic conditions of Hassner and Boerwinkle (bromine plus sodium azide and hydrochloric acid in nitromethane-dichloromethane) or Ponsold (A-bromosuccinimide or A-bromoacetamide in chloroform contain-... 

Substituted aryl hydrazones can be converted to geminal difluondes in satis factory yields by molecular fluorine [H4, iodine fluoride [ 5], and N bromo-suc-cinimide-pyridinium polyhydrogen fluoride or A -bromosuccinimide-polyvi-nylpyridinium polyhvdrogen fluoride [5(5] (equation 21) (Table 6)... 

A-Bromosuccinimide provides a low concentration of molecular bromine, which reacts with alkenes by a mechanism analogous to that of other free-radical halogenations. 

A/-Bromosuccinimide will be seen again as a reagent for selective bromination in Section 11.12. 

Halogenation (Section 11.12) Free-radical halo-genation of alkylbenzenes is highly selective for substitution at the benzylic position. In the example shown, elemental bromine was used. Alternatively, A/-bromosuccinimide is a convenient reagent for benzylic bromination. 

A certain compound A, when treated with A-bromosuccinimide and benzoyl peroxide under photochemical conditions in refluxing carbon tetrachloride, gave 3,4,5-tribromobenzyl bromide in excellent yield. Deduce the structure of compound A. 

Campaigne et al. have used 3-thenyl bromide obtained by benzoyl peroxide-catalyzed, side-chain bromination of 3-methylthiophene with A -bromosuccinimide, as a starting material for 3-substituted thiophenes. - 22 3-Methylthiophene is now prepared commercially from itaconic acid. The reactive halogen in 3-thenyl bromide could be directly reacted with a variety of nucleophiles, such as cyanide, or malonate, to give more complex 3-substituted compounds. 3-Thenyl bromide was converted by the Sommelet reaction to 3-thio-phenealdehyde which, with silver oxide, was oxidized to 3-thio-... 

This activation of the ortho position is most strikingly illustrated in the reactivity of 2,5-dimethylthiophene, which competitive experiments have shown to undergo the SnCb-catalyzed Friedel-Crafts reaction more rapidly than thiophene and even 2-methylthiophene. The influence of the reagent on the isomer distribution is evident from the fact that 2-methoxythiophene is formylated and bromi-nated (with A -bromosuccinimide) only in the 5-position. Similarly, although 3-bromo-2-methylthiophene has been detected in the bromi-nation of 2-methylthiophene with bromine, only the 5-isomer (besides some side-chain bromination) is obtained in the bromination of alkylthiophenes with A -bromosuccinimide. ° However, the mechanism of the latter type of bromination is not established. No lines attributable to 2-methyl-3-thiocyanothiophene or 2-methyl-3-chIoro-thiophene could be detected in the NMR spectra of the substitution products (5-isomers) obtained upon thiocyanation with thiocyanogen or chlorination with sulfuryl chloride. 2-Methyl- and 2-ethyl-thiophene give, somewhat unexpectedly, upon alkylation with t-butyl chloride in the presence of Feds, only 5-t-butyl monosubstituted and... 

Aldehydes are also obtained from thenylalcohols by oxidation with selenium dioxide,A"-bromosuccinimide, persulfate,lead dioxide, and nitric acid. ... 

Bromination of the methyl group of (249) with A -bromosuccinimide, followed by reaction with excess secondary amine gave (250) which shows combined analgesic and antitussive properties. The Reformatsky reaction has also been used for the preparation of 2-amino-ethyl 3,3-diaryl-3-hydroxypropanates (251) as well as their dehydration products. The propene amides (252) have also been prepared for pharmacological evaluation. In l-methyl-3-bis (2-thienyl)-... 

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