Brominations A -bromosuccinimide

The direct oxidation of the tr-adduct 1 with bromine, A -bromosuccinimide or, preferably, lead tetraacetate in the presence of acetic acid afforded jS-acetoxy amines 2 by an overall syn addition. The acetate reduction with lithium aluminum hydride gave the corresponding )S-hy-droxy amines 360 62. 

When halogenation is carried out in the presence of a nucleophile, interception of cation intermediates occurs and results in the formation of monohalogenated products. This was observed when bromine addition to 4,5-homo-l,7a-diazoindene was carried out in ethanol to give the corresponding (l-bromo-2-ethoxyalkyl)cyclopropane as the main product. " Similar products were obtained on treatment of vinylcyclopropanes with A-bromosuccinimide or N-chlorosuccinimide in water, methanol, and acetic acid, and N-bromoacetamide in water. Monohalides were also obtained when 3-acetoxy-6,6-di-phenylbicyclo[3.1.0]hexene derivatives, e.g. 1, and similar compounds reacted with bromine, A-bromosuccinimide in tetrahydrofuran, and sulfuryl chloride in carbon tetrachloride. ... 

Either elemental bromine (much cheaper) or A-bromosuccinimide may be used as the reagent for benzylic bromination. A-Bromosuccinimide is preferred for ally lie 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. 

Other Reactions.—An Indian group have investigated three means of effecting hydroxylation of unsaturated acids sulphation and hydrolysis, autoxidation and reduction, and allylic bromination (A-bromosuccinimide) and hydrolysis. French chemists have prepared and examined some mono-and di-oxo-enoic acids. They find that unsaturated 1,4-dioxo-acids rearrange spontaneously to 1,2-dioxo-isomers ... 

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. 

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. 

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 " ... 

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

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-... 

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. 

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... 

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)-... 

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). 

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