With V-bromosuccinimide

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. 

A rather broadly applicable method leading to products which can be further modified starts from 3,8-diaryl-l,2-diazacycloocta-2,8-dienes 4.23,24 With /V-bromosuccinimide dihalogenation occurs which, after a double dehydrohalogenation, gives 3,8-diphenyl-1,2-di-azocine (5 Ar = Ph, X = H) in low yield. The reaction with sulfuryl chloride to give tetra-... 

Alternatively, the thiazolotriazine ring was prepared from l-nitro-2-aminonaphthalene with an isothiocyanate to give naphthylpyrimidine 669, whose reaction with phenacyl bromide gave thiazoline 670. Reduction with stanous chloride and cyclization with (V-bromosuccinimide gave naphthothiazolotriazine 671 (74JIC631) (Scheme 138). 

The optically active D- and L-em/rn.i-2-morpholmones 1 (only the d-erythro series is depicted) are efficiently brominated with (V-bromosuccinimide to afford the bromo derivatives 2 (X = Br) that serve as versatile precursors for electrophilic glycine templates which permit construction of either d- or L-a-atnino acids in high optical purity71. The corresponding chlorides 2 (X = Cl) are similarly obtained by chlorination of 1 with tert-butyl hypochlorite71. 

Besides the use of porphyrins as azomethinic ylide derivatives, the porphyrin macrocycle can also be used to generate porphyrinic nitrile oxides 55 (Scheme 17) <04RCB(E)2192>. Thus, the treatment of oxime 54 with /V-bromosuccinimide in the presence of triethylamine, led to the formation of nitrile oxide 55, which was trapped in 1,3-DC reactions with dimethyl maleate and 2,5-norbomadiene to afford 56 and 57, respectively. In the reaction with 2,5-norbomadiene, if an excess of 55 was used, then the corresponding bis-adduct was obtained in good yield. 

Cyclization of oximes containing y-,d-, or oo-alkenyl substituents, upon treatment with /V-bromosuccinimide (NBS) or iodine leads in good yields to the corresponding cyclic nitrones or their dimeric H- bonded hydriodide salts (290). 

Treatment of thioglycosides with /V-bromosuccinimide (NBS) in the presence of diethylaminosulfur trifluoride (DAST) or HF-pyridine complex furnishes glycosyl fluorides.23 These can be activated with AgC104/SnCL in the presence of another... 

The reactions involving bromine or chlorine generate hydrogen halide and are autocata-lytic. Reactions with /V-bromosuccinimide or tetrabromocyclohexadienone form no hydrogen bromide, and these reagents may therefore be preferable in the case of acid-sensitive compounds. 

Halofluorinations take place, as a rule, regioselectively (Markovnikov addition), the olefinic carbons can be substituted with a variety of substituents ranging from alkyl or aryl groups to different electron-withdrawing functions see for example refs 31 and 178-180. Bromo-fluorination of 4-/m-butyl-l-methylcyclohexene with /V-bromosuccinimide in 70% hydrogen fluoride/pyridine gave two stereoisomers 1 and 2.181... 

A certain compound A, when treated with (V-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. 

Bromomethylbenzo[6]thiophenes are readily obtained in high yields by treatment of the corresponding methyl compound with. V-bromosuccinimide in the presence of benzoyl peroxide.91,105,298 343,4i3,447,487,489-492,517,518 Applied to 3-methylbenzo[6]thiophene, this procedure affords 2-bromo-3-methylbenzo[6]thiophene (12%), in addition to the required product the yield of nuclear substituted product rises to 78% when peroxides are excluded.487 When 3,5-dimethylbenzo[6]thiophene is treated with W-bromosuccinimide, the 3-methyl group is preferentially brominated,489 but in the cases of other 5-alkyl-3-methylbenzo[6]thiophenes inseparable mixtures of products are formed.292 The above reaction has also been applied to... 

Oximo groups cannot themselves be used instead of the carbonyl functions in reactions of this kind, because, with /V-bromosuccinimide or bro-... 

The HF-SbF5 superacid finds numerous additional useful applications in other fluorination reactions. Ally lie amines are hydrofluorinated in HF-SbF5 (7 1) to give /3-fluoro-substituted products (—20°C, 24—85% yields).545 HF-SbF5 in combination with /V-bromosuccinimide transforms allylic amines and haloalkyl amines into gem-difluoro derivatives (0°C or 20°C, 43-70% yield).546... 

Stable dialkyl ether poly(hydrogen fluoride) complexes have been shown to be convenient and effective fluorinating agents.553 Various open-chain and cyclic alkenes undergo hydrofluorination with dimethyl ether-5 HF (DMEPHF) atroom temperature to furnish the corresponding fluoro derivatives in high yields (73-94%) with excellent selectivities. The fluorination of secondary and tertiary alcohols exhibit similar features. Bromofluorination of alkenes can also carried out with DMEPHF in combination with /V-bromosuccinimide. The homologous diethyl ether and dipropyl ether complexes are also suitable for fluorinations. 

In a different sequence of reactions, N-acetylation of 274 and exposure of the intermediate imide 275 to ethanolic KOH gave a mixture (about 2 1) of the desired carboxylic acid 276 together with the starting lactam 274 via the non-selective hydrolysis of the imide moiety of 275 (148a,c). When 276 was treated with /V-bromosuccinimide (NBS), an intermediate bromolactone was produced which was heated at reflux in pyridine in the presence of DBU to give 277. The conversion of the lactone 277 to the lactam 278 was effected by heating 277 in aqueous NaOH followed by protection of the resulting allylic alcohol function as a tetrahydropyranyl ether. 

The diastereoselective alkylation of /V-acyloxazolidinones enolates was examined first. Lithium enolates of 107 were reacted with a variety of alkyl halides, and alkylation products were formed with excellent diastereoselectivities (94-99% de). Hydrolysis gave optically pure carboxylic acids, and the chiral auxiliary was recovered for reuse almost quantitatively.105-106 Highly diastereoselective bromination was also achieved by reaction of the boron enolate of 107 with /V-bromosuccinimide (NBS) (98% de). Optically pure amino acids could be accessed by simple synthetic transformations (Scheme 24.26).106... 

Friedel-Crafts acetylation of l-methyl-4,5,6,7-tetrahydrobenzo[c]-thiophene is reported10 to give l-acetyl-3-methyl-4,5,6,7-tetrahydro-benzo[c]thiophene. Successive treatment of methyl 4,5,6,7-tetra-hydrobenzo[c]thiophene- 1-carboxylate with /V-bromosuccinimide and sodium methoxide gives benzo[c]thiophene-l-carboxylic acid.16,38... 

Stereoselective conversion of 2-amino-3-hydroxy-4-pentenoic acid35 into the highly functionalized 2-furanones with the m-(4-hydroxy, 4-haloalkyl) relationship has been obtained through electrophile-promoted cyclization, due to the propensity of the hydroxy group to direct a cis substitution. Thus, treatment of (2.S, 3S)-2-tcrt-butoxycarbonylamino-3-hydroxy-4-pentenoic acid (32) with /V-bromosuccinimide in tetrahydrofuran gives the corresponding (35,4/ ,55 )-bromolactone 33 in 70% yield as the sole product35. 

Halogenations with A/-halogenosuccinimides have also been studied. Treatment of 2-methyl- and 2,5-dimethylpyrazine with one equivalent of A -chlorosuccinimide and a small quantity of benzoyl peroxide gave the unstable 2-chloromethyl (679, 690) and 2-chloromethyl-5-methylpyrazine (679). 2-Ethyl-3-methylpyrazine and 23-diethylpyrazine with V-bromosuccinimide in the presence of benzoyl peroxide gave 2-(l -bromoethyl)-3-methyl(and 3-ethyl)pyrazine, respectively (691,692). 

Peroxy adds may epoxidize unsaturated ketones [299, 332], but a concomitant Baeyer-Villiger reaction is possible [254] (equations 389 and 391). Other ways of forming epoxy ketones are reactions with salts of hypochloric acid [691, 704] and with V-bromosuccinimide [746]. Mesityl oxide is converted into its epoxide, as shown in equation 437 [142, 220, 254, 746]. 

Allylic bromination of glycals 10 and 18 was investigated under the usual Wohl-Ziegler conditions with /V-bromosuccinimide (NBS/CCLt/reflux) in the presence of azobi-sisobutyronitrile (AIBN) as initiator. Although both bromides were easily formed in this reaction, the nonfluorinated one appeared to be unstable and could not be isolated [70], The parent 10-CF3-16-bromo derivative 22 was also obtained in good yield (72%) (see Scheme 6.12). The compound could be purified by crystallization and stored for several weeks at 0°C. Clearly, the electron-withdrawing character of the CF3 group makes the allyl bromide less labile. 

The treatment of 1 with bromine in DMF at 0 °C afforded a dihydrofuran product (122) as a mixture of C-15 a and (5 isomers instead of the expected 2-bromofuran product (Scheme 19) [50]. However, treatment of 1 with /V-bromosuccinimide (NBS) in acetonitrile gave the desired 2-bromofuran product (123) in 38% yield. From 123, Stille coupling with tributylvinyl tin in the presence of Pd(PPh3)4 afforded the 2-vinylfuran product (124) in 58% yield [44],... 

Formation of methylcyclopropane complexes and reactions of these metal alkyls competes with direct conversion of the homoallylmetal complex. Thus 1,2-hydrozirconation of 1,3-dienes with Schwartz s reagent [bis(cyclopentadienyl)zirconium chloride hydride] leads to homoallyl-zirconium complexes 1 which upon treatment with V-bromosuccinimide give the corresponding l-bromobut-3-enes 2 and the isomeric (bromomethyl)cyclopropanes 3 via intramolecular ring closure. ... 

A/-Bromoindoles 14 were synthesized by bromination of 2-ethylsulfonyl-3-methyl- and -3-phenylindoles 13 with /V-bromosuccinimide (77CPB2350) (Scheme 4). 

Bromo-4-nitropyrazole 19 is obtained by bromination of 4-nitropyra-zole with sodium hypobromite in water-acetic acid [55LA(593)179]. 3,5-Dimethyl-4-tropylpyrazole is brominated with /V-bromosuccinimide to form a mixture of Af-bromoderivative 20,4-bromo-3,5-diethylpyrazole, and 7-tropylsuccinimide (64BCJ1018) (Scheme 7). 

Photobromination of 5,6-dimethyl-1,2,4-triazine with /V-bromosuccinimide and sulfur in carbon tetrachloride for 24 hours gives 5,6-bis(dibromomethyl)-1,2,4-triazine (3) in 24% yield.295 Treatment of the telrabromide 3 with sodium iodide yields the quinodimethane 4, which is trapped by reaction with /V-phenylmaleimide or benzoquinone, elimination of hydrogen bromide giving the isolated products 5 and 6.295... 

Stereoselective, radical bromination of cyclic acetals with /V-bromosuccinimide is one of the steps in the synthesis of enantiomerically pure derivatives of pyruvic acid103. Asymmetric bromination in the a-position of dioxolanes is used for the preparation of optically active carbonyl cotnpunds1"4 The mechanism involves bromination of the low concentration ring-opened enols106. 

The bromofluorination of methylenecyclohexanes can be carried out with /V-bromosuccinimide and triethylamine/hydrogen fluoride 688 for example, the formation of 1 from l-methyl-2-methylenecyclohexane. 

Tryptophan-59 has been modified by formylation, with the formyl group replacing the NH proton on the indole ring, and oxidation with V-bromosuccinimide (NBS). In both cases the hydrogen bond to the buried heme propionic acid is broken, and the molecule undergoes the change in properties outlined in Table XV. Reductase activity is impaired, and the oxidase reaction is also affected somewhat The reaction is slower for any given cytochrome c concentration short of saturation, but the Vm x is the same as for unmodified cytochrome c. The NBS story... 

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