A’-Bromosuccin imide

Aromatic thio orthoesters are successfully converted into trifluoromethyl arenes by treatment with a pyridinium polyhydrogen fluoride-A -halo imide reagent. The reactions are conducted at -30 to -20 °C, and the nature of A-halo imide is critical both 1,3-dibromo-5,5-dimethylhydantoin and A-bromosuccin-imide give similar yields of trifluoromethyl compounds [5] (equation 7)... 

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. 

As an alternative to the use of quaternary ammonium tribromide, A -bromosuccin-imide tetra-n-butylammonium bromide converts alkenes into the dibromoalkanes generally in high yield (>90%) [8]. It is probable that the ammonium tribromide is formed in situ. 

Hydroximoyl halides (4) are conveniently prepared by halogenation of the respective aldoximes (5), for which a number of halogenating agents such as chlorine (38), ferf-butyl hypochlorite, A -chlorosuccinimide (NCS) (39), or A -bromosuccin-imide (NBS) (40) have been employed. A plausible mechanistic course involves Hal addition and proton loss to give an a-halonitroso compound, often observed as a transient blue-green color, as shown for the chloro case (Scheme 6.1). 

Comparison of bromofluorinations of six substituted ethyl cinnamates using A-bromosuccin-imide with hydrogen fluoride/pyridine and hydrogen fluoride/tetrahydrofuran (several molar ratios) also shows a Markovnikov-type regioselectivity. The stereoselectivity depends on several factors 184... 

Selected examples are given in Table 9 for bromofluorinations of alkenes using A-bromosuccin-imide in combination with 70% hydrogen fluoride/pyridine (Method A) and hydrogen fluo-ride/polyvinylpyridine (Method B), respectively. Table 10 shows examples of the selective monoaddition of in situ produced halofluorides (70 % hydrogen fluoride/pyridine and A-iodo-. A-bromo- or /V-ehloro-succinimide) to symmetrically substituted alkynes. 

Halohydrin formation with subsequent reductive dehalogcnation represents an interesting variation on the theme. For example, when the enone rac-1 was treated with A -bromosuccin-imide in aqueous dimethyl sulfoxide, the bromohydrin roc-2 was formed, predominantly as one diastereomer (the relative configuration at C-3 was not established)23. Reduction with tri-butyltin hydride gave the diastereomeric products exo-3 and endo-3 in 27% and 63% yield, respectively. Here, the product distribution can be explained by the preferred attack of the hydride reagent on the exo-face of the intermediate bicyclic carbon radical, i.e., by kinetic control. Thus, the predominant endo-orientation of the 2-(2-hydroxypropyl) substituent at C-3 was achieved, in contrast to what may be expected from a reversible, i.e., thermodynamically controlled, hydration of the enone rac-1. 

For synthetic purposes cyclized radicals are preferentially trapped by chlorine [16], bromine [60], or iodine atom donors [54] to provide y9-functionalized tetrahy-drofurans, for instance halides 35-37 (Scheme 9), which serve as building blocks for subsequent ionic or free-radical reactions. This radical version of the classical halogen cyclization (Bartlett reaction [61]) is particularly useful if functionalized tetrahydrofurans can be obtained from terminal alkyl- or aryl-substituted alkenols. If these compounds are reacted for example with iodine or with A -bromosuccin-imide, tetrahydropyrans are formed from ionic cyclofunctionalizations [62], If, however, the corresponding alkenols are converted into a thiohydroxamic acid... 

Treatment of zirconacyclopentanes with bromine, iodine, or A-bromosuccin-imide (NBS) gives the 1,4-dihalide in good yield. Selective monohalogenation... 

Related Reagents. A-Bromosuccinimide-dimethylform-amide A-bromosuccinimide-dimethyl sulfide A-bromosuccin-imide-hydrogen fluoride A-bromosuccinimide-sodium azide triphenylphosphine-A-bromosuccinimide. 

The pyridine was a pure product, b.p. 113-115°, obtained from Mallinckrodt Chemical Company and used as supplied. The methylene chloride (technical grade) and N-bromosuccin-imide (practical grade) were obtained from the Matheson Company and used as received. 

Oxidation of a-diketone hydrazone imines with cuprammonium salts gives 2/f-triazoles. With substituted imines (using W-bromosuccin-imide as oxidant) 1,2-disubstituted triazolium salts are obtained (Scheme 33). ... 

Eghbali et al. [185] have reported the details of a highly efficient method for converting alkenes and C02 into CCs directly in water, by using N-bromosuccin-imide (NBS) together with l,8-diazabicyclo[5.4.0]undecen-7-ene (DBU), or a catalytic quantity of bromide ion together with aqueous H202. 

Kimura Y, Alfano JC, Walhout PK, Barbara PF (1994) Ultrafast transient absorption spectroscopy of the solvated electron in water. J Phys Chem 98 3450-3458 Li X, Sevilla MD, Sanche L (2003) Density functional theory studies of electron interaction with DNA can zero eV electrons induce strand breaks J Am Chem Soc 125 13668-13699 Lind J, Shen X, Eriksen TE, Merenyi G, Eberson L (1991) One-electron reduction of N-bromosuccin-imide. Rapid expulsion of a bromine atom. J Am Chem Soc 113 4629-4633 Marasas RA, lyoda T, Miller JR (2003) Benzene radical ion in equilibrium with solvated electrons. J Phys Chem A 107 2033-2038... 

The choice of the solvent and of the electrophile is very important since the reaction can be carried out under kinetic or thermodynamic control. The possibility of equilibrating a cyclic intermediate strongly influences the regio- and stereochemistry of the reaction. The presence of a base in an aqueous medium generally results in kinetic control of the cyclization process18, while reversible conditions are favored by iodine in acetonitrile19. In addition, A -iodosuccin-imide in chloroform, iodine in chloroform and iodine in tetrahydrofuran/pyridine are considered to give cyclizations under kinetic control. On the other hand, the use of AT-bromosuccin-imide or bromine affords lower selectivity. 

In the course of their application to the natural product, Danishefsky provided a total synthesis of (+ )-lincosamine (Scheme 30) (83JA6715 85JA1274). An intermolecular hetero Diels-Alder reaction of the diene mixture 195 with crotonaldehyde (210) under the influence of trifluoroacetic acid at -78°C gave a 67% yield of the 2-[( )-l-propenyl]pyrone 211. Reduction of the ketone 211 by Luche s procedure (79JA5848) followed by benzoylation afforded the galactal derivative 212. Treatment of 212 with m-chloroperbenzoic acid in anhydrous methanol followed by benzoylation afforded the methyl galactoside 213. Reaction of 213 with N-bromosuccin-imide in the presence of wet acetic acid produced a single bromohydrin (214). 

Diarylacetylenes are converted in 55-90% yields into a-diketones by refluxing for 2-7 h with thallium trinitrate in glyme solutions containing perchloric acid [413. Other oxidants capable of achieving the same oxidation are ozone [84], selenium dioxide [509], zinc dichromate [660], molybdenum peroxo complex with HMPA [534], potassium permanganate in buffered solutions [848, 856, 864,1117], zinc permanganate [898], osmium tetroxide with potassium chlorate [717], ruthenium tetroxide and sodium hypochlorite or periodate [938], dimethyl sulfoxide and iV-bromosuccin-imide [997], and iodosobenzene in the presence of a ruthenium catalyst [787] (equation 143). 

Auerbach, J. Weissman, S. A. Blacklock, T. J. Angeles, M. R. Hoogsteen, K., N-Bromosuccin-imide / Dibromodimethylhydantoin in Aqueous Base A Practical Method for the Bromination of Activated Benzoic Acids. Tetrahedron Lett. 1993, 43, 931. 

The Si—H group can be converted to the Si—group by a variety of methods. In the disilane series, both halogens (42, 76) and iV-bromosuccin-imide (NBS) (42) have been used effectively. The same reagents have been employed with higher polysilanes (58). 

The reaction is readily monitored by the characteristic changes in the uv spectrum. A more reliable source of positively charged bromine is N-bromosuccin-imide, which has often been used for cleavage at tryptophan ... 

The only approach to the synthesis of the natural arylnaphthalides has been the preparation of two fully methylated derivatives shown in Scheme XI (65). A 2,7-diarylpent-4-enenitrile (68) was cyclized to the phenyltetralin (69). Bromination and aromatization with N-bromosuccin-imide then gave the phenylnaphthalene derivative (70). Finally basic hydrolysis produced the phenylnaphthalide (71). 

A different approach using alkene derivatives involved allylic substitution reactions. Ethyl cyclohex-3-en-l-carboxylate (7.51) reacted with N-bromosuccin-imide to give 7.52.26 This allowed reaction with potassium phthalimide to give 7.53 in an overall yield of 41%. Catalytic hydrogenation and treatment with methylamine led to ds-3-aminocyclohexane-l-carboxylic acid, 7.22.26... 

The allylic bromination of cyclohexene was successfully done using co(polyethylene-N-bromomaleimide). When polymeric AT-bromosuccin-imide ( -NBS) was used for bromination of cumene, products other than those of benzylic bromination were also formed (Scheme 12-10) (Yaroslavsky et aL, 1970a,b). The change in mechanism has been attributed to the polar environment provided by neighboring succinimide units in (p)-NBS. Polymeric A/-chloromaleimide, synthesized by Yaroslavsky and Katchalski (1972), on reaction with ethylbenzene, also gave products due to aromatic substitution. 

---