N-Bromosuccinimide (NBS) is a brominating and oxidizing agent that is used as source for bromine in radical reactions (for example: allylic brominations) and various electrophilic additions. The NBS bromination of substrates such as alcohols and amines, followed by elimination of HBr in the presence of a base, leads to the products of net oxidation in which no bromine has been incorporated.
An efficient and user-friendly procedure has been developed for the oxidative deprotection of tetrahydropyranyl (THP) ethers with N-bromosuccinimide (NBS) using β-cyclodextrin (β-CD) in water. A series of tetrahydropyranyl ethers were oxidatively deprotected at room temperature in impressive yields.
M. Narender, M. S. Reddy, K. R. Rao, Synthesis, 2004, 1741-1743.
N-alkoxyamides conveniently afford the corresponding carboxylic esters in the presence of NBS in toluene via oxidative homocoupling and the subsequent thermal denitrogenation. Even substrates bearing a bulky or long-chain substituent gave products in good yields in this convenient and economic approach to a direct transformation of an alkoxyamide moiety into the carboxylic ester functional group.
N. Zhang, R. Yang, D. Zhang-Negrerie, Y. Du, K. Zhao, J. Org. Chem., 2013, 78, 8705-8711.
An efficient, metal and base-free, chemoselective reaction of boronic acids with cyanamidyl/arylcyanamidyl radicals provides primary aryl-, heteroaryl-, and alkyl amines at ambient temperature within 1 h. The reaction is mediated by PIFA and NBS.
N. Chatterjee, M. Arfeen, P. V. Bharatam, A. Goswami, J. Org. Chem., 2016, 81, 5120-5127.
A stereoselective synthesis of dienes from aldehydes and N-allylhydrazine derivatives offers high levels of (E)-stereoselectivity for a variety of substrates. Addition of a dienophile to the reaction mixture allows a one-flask diene synthesis-cycloaddition sequence.
D. A. Mundal, K. E. Lutz, R. J. Thomson, Org. Lett., 2009, 11, 465-468.
An efficient one-pot transformation of β-hydroxycarbonyl compounds to α-brominated 1,3-dicarbonyl compounds is achieved with MoO2Cl2 in the presence of N-bromosuccinimide. All the reactions were carried out under mild conditions and provide good yields. No bromination occurs at benzylic and allylic positions.
K. Jeyakumar, D. K. Chand, Synthesis, 2009, 306-310.
Selective oxyhalogenations of alkynes were achieved in water under very mild conditions in the presence of inexpensive halogenating reagents, such as N-bromosuccinimide and N-chlorosuccinimde, and FI-750-M as amphiphile. No halogenation at the aromatic rings was detected. Reaction medium and catalyst can be recycled.
L. Finck, J. Brals, B. Pavuluri, F. Gallou, S. Handa, J. Org. Chem., 2018, 83, 7366-7372.
A triphenylphosphine oxide catalyzed reductive halogenation of an α,β-unsaturated ketone with trichlorosilane as the reducing reagent and an N-halosuccinimide as the electrophilic halogen source enables a selective synthesis of unsymmetrical α-haloketones.
Z. Lao, H. Zhang, P. H. Toy, Org. Lett., 2019, 21, 8149-8152.
Reliable, operationally simple, catalytic α-selective hydroalumination reactions proceed in the presence of diisobutylaluminum hydride and (Ni(dppp)Cl2), and, unlike uncatalyzed transformations, generate little or no alkynylaluminum byproducts. The derived α-vinyl halides and boronates can be synthesized through direct treatment with the appropriate electrophiles.
F. Gao, A. H. Hoveyda, J. Am. Chem. Soc., 2010, 132, 10961-10963.
Trapping of a diazo species in an intermolecular fashion by two independent ion species in tandem at the carbene center installs an electrophile and a nucleophile on the same carbon. This metal-free concept enables regioselective syntheses of various vinyl halides, vinyl sulfones, and alkyne derivatives.
D. P. Ojha, K. R. Prabhu, Org. Lett., 2015, 17, 18-21.
Unsaturated compounds such as alkenes, alkynes, allenes, and methylenecyclopropanes (MCPs) can be dibrominated within minutes by NBS and lithium bromide in THF at room temperature in good to excellent yields under mild conditions.
L.-X. Shao, M. Shi, Synlett, 2006, 1269-1271.
The use of N-bromosuccinimide enables a metal-free one-pot strategy for the synthesis of pharmaceutically important α-amino ketones from readily available benzylic secondary alcohols and amines. This reaction proceeds via three consecutive steps involving oxidation of alcohols, α-bromination of ketones, and nucleophilic substitution of α-bromo ketones to give α-amino ketones.
S. Guha, V. Rajeshkumar, S. S. Kotha, G. Sekar, Org. Lett., 2015, 17, 406-409.
A combination of N-bromoimide and DBU enables allylic amination reactions of alkenes, in which both internal and external nitrogen nucleophiles can be installed directly. Dual activation of NBS or NBP by DBU leads to more electrophilic bromine and more nucleophilic nitrogen atoms simultaneously. This protocol provides a complementary access to allylic amination under mild conditions.
Y. Wei, F. Liang, X. Zhang, Org. Lett., 2013, 15, 5186-5189.
A convenient and efficient method for aminobromination of alkylidenecyclopropanes is reported. This is exemplified in the stereoselective preparation of N-[(Z)-3-bromobut-3-en-1-yl]-p-toluenesulfonamides by using p-toluenesulfonamide and N-bromosuccinimide (NBS) as nitrogen and bromine sources, respectively.
X. Huang, W.-J. Fu, Synthesis, 2006, 1016-1017.
In a continuous-flow protocol for the bromination of benzylic compounds with only a small excess of N-bromosuccinimide, the radical reactions were activated with a readily available household compact fluorescent lamp (CFL) using a simple flow reactor design based on transparent fluorinated ethylene polymer tubing. All of the reactions were carried out using acetonitrile as the solvent, thus avoiding hazardous chlorinated solvents such as CCl4.
D. Cantillo, O. de Frutos, J. A. Rincon, C. Mateos, C. O. Kappe, J. Org. Chem., 2014, 79, 223-229.
The Lewis base Trip-SMe (Trip = triptycenyl) catalyzes an electrophilic halogenation of unactivated aromatic compounds using N-halosuccinimides (NXS) at ambient temperature in the presence of AgSBF6 as source of a non-coordinating anion. The π system of the triptycenyl functionality exerts a crucial role for the enhancement of electrophilicity.
Y. Nishii, M. Ikeda, Y. Hayashi, S. Kawauchi, M. Miura, J. Am. Chem. Soc., 2020, 142, 1621-1629.
A highly regioselective bromination of activated aromatic compounds has been accomplished using N-bromosuccinimide in tetrabutylammonium bromide. Predominant para-selective monobromination of activated aromatics, rate acceleration for less reactive substrates on addition of acidic montmorillonite K-10 clay, with or without microwave assistance, are the notable features of this protocol.
N. C. Ganguly, P. De. S. Dutta, Synthesis, 2005, 1103-1108.
The use of a hexafluoroisopropanol as solvent enables a mild and regioselective halogenation of a broad range of arenes and heterocycles with N-halosuccinimides in good yields. In addition, the versatility of the method is demonstrated by the development of one-pot sequential dihalogenation and halogenation-Suzuki cross-coupling reactions.
R.-J. Tang, T. Milcent, B. Crousse, J. Org. Chem., 2018, 83, 930-938.
A highly para-selective halogenation of arenes bearing electron-donating coordinating groups in the presence of a dimidazolium salt rpovides p-haloarenes in good yields. A plausible mechanism for the catalytic reaction is proposed.
J. Chen, X. Xiong, Z. Chen, J. Huang, Synlett, 2015, 26, 2831-2834.
Highly deactivated aromatic compounds were smoothly monobrominated by treatment with N-bromosuccinimide (NBS) in concentrated sulfuric acid. Mild reaction conditions and simple workup provides a practical and commercially viable route for the synthesis of bromo compounds of deactivated aromatics in good yields.
K. Rajesh, M. Somasundaram, R. Saiganesh, K. K. Balasubramanian, J. Org. Chem., 2007, 72, 5867-5869.
N-Halosuccinimides are efficiently activated in trifluoromethanesulfonic acid and BF3-H2O, allowing the halogenations of deactivated aromatics. BF3-H2O is more economic, easy to prepare, nonoxidizing, and offers sufficiently high acidity.
G. K. S. Prakash, T. Mathew, D. Hoole, P. M. Esteves, Q. Wang, G. Rasul, G. A. Olah, J. Am. Chem. Soc., 2004, 126, 15770-15776.
Aryl and heteroaryl boronic acids react with N-iodosuccinimide and N-bromosuccinimide to give the corresponding iodo- and bromo-arenes in good to excellent yields. The reaction is usually highly regioselective and yields only the ipso-substituted product.
C. Thiebes, G. K. Surya Prakash, N. A. Petasis, G. A. Olah, Synlett, 1998, 141-142.
A high-yielding, general, and practical ortho bromination and iodination reaction of different classes of aromatic compounds occurs by Rh(III)-catalyzed C-H bond activation methodology.
N. Schröder, J. Wencel-Delord, F. Glorius, J. Am. Chem. Soc., 2012, 134, 8298-8301.
Using cyano as the directing group, a palladium-catalyzed ortho-halogenation (I, Br, Cl) reaction gave good to excellent yields. The method is compatible to arylnitriles with either electron-withdrawing or electron-donating groups. The present method was successfully applied to the synthesis of the precursors of paucifloral F and isopaucifloral F.
B. Du, X. Jiang, P. Sun, J. Org. Chem., 2013, 78, 2786-2791.
An efficient protocol for a highly stereoselective one-pot synthesis of (E)-β-aryl vinyl iodides and (E)-β-aryl vinyl bromides from styrenes is based on a ruthenium-catalyzed silylative coupling followed by a N-halosuccinimide-mediated halodesilylation reaction.
P. Pawluć, G. Hreczycho, J. Szudkowska, M. Kubicki, B. Marciniec, Org. Lett., 2009, 11, 3390-3393.
Using triethylamine as catalyst in Hunsdiecker reactions with N-halosuccinimides as Br+ or I+ source, cinnamic acids, and propiolic acids are converted to the corresponding α-halostyrenes and 1-halo-1-alkynes in good isolated yields within 1-5 min.
J. Prakash, S. Roy, J. Org. Chem., 2002, 67, 7861-7864.
(E)-β-Arylvinyl bromides were readily prepared in a short reaction time (1-2 min) by microwave irradiation of the corresponding 3-arylpropenoic acids in the presence of N-bromosuccinimide and a catalytic amount of lithium acetate.
C. Kuang, Q. Yang, H. Senboku, M. Tokuda, Synthesis, 2005, 1319-1325.
An efficient synthesis of α-iodo/bromo-α,β-unsaturated aldehydes/ketones directly from propargylic alcohols is catalyzed collaboratively by Ph3PAuNTf2 and MoO2(acac)2, and Ph3PO as an additive helps suppress undesired enone/enal formation. Notable features of this method include low catalyst loadings, mild reaction conditions, and mostly good diastereoselectivity.
L. Ye, L. Zhang, Org. Lett., 2009, 11, 3646-3649.
A regio- and stereoselective iodination, along with some examples for bromination, of readily available acrylamides proceeds under mild conditions via a Rh(III)-catalyzed C-H-activation/halogenation mechanism. The reaction represents a rare example of a direct halogenation of electron-poor acrylic acid derivatives to access a variety of differently substituted Z-haloacrylic acid derivatives.
N. Kuhl, N. Schröder, F. Glorius, Org. Lett., 2013, 15, 3860-3863.
In an NBS-promoted allyloxyl addition-Claisen rearrangement-dehydrobromination cascade reaction, more than 20 substituted alkynylsulfonamides were reacted with allyl alcohols to generate (2Z)-2,4-dienamides in good yields. Theoretical calculations suggested that a [3,3] sigmatropic rearrangement be the rate-limiting step.
R. Ding, Y. Li, C. Tao, B. Cheng, H. Zhai, Org. Lett., 2015, 17, 3994-3997.
A fast and convenient one-step procedure allows the conversion of α,β-unsaturated carbonyl compounds into their corresponding bromo-enones at room temperature under very mild conditions in high yields using NBS-Et3N • 3 HBr in the presence of potassium carbonate in dichloromethane.
D. Jyothi, S. HariPrasad, Synlett, 2009, 2309-2311.
A mild, one-pot cyanoimidation of aldehydes using cyanamide as a nitrogen source and NBS as an oxidant was achieved in high yields without the addition of a catalyst. Subsequently, the substituted N-cyanobenzimidate products may also undergo a cyclization reaction to give 1,2,4-triazole derivatives in high yields.
P. Yin, W.-B. Ma, Y. Chen, W.-C. Huang, Y. Deng, L. He, Org. Lett., 2009, 11, 5482-5485.
Sm(OTf)3 is an effective catalysts for a versatile and efficient halogen-promoted highly regio- and stereoselective Friedel-Crafts (F-C) alkylation of electron-rich arenes with alkenes and α,β-unsaturated carbonyl compounds in the presence of NBS or I2 as halogen sources.
S. Haira, B. Maji, S. Bar, Org. Lett., 2007, 9, 2783-2786.
A new silver-catalyzed highly regio- and stereoselective difunctionalization reaction of simple terminal alkynes gives (Z)-β-haloenol acetate derivatives in good yields. The resulting products are versatile intermediates in organic synthesis.
Z. Chen, J. Li, H. Jiang, S. Zhu, Y. Li, C. Qi, Org. Lett., 2010, 12, 3262-3265.
A zwitterion-catalyzed intermolecular bromoesterification of alkenes works with acid and olefin in an equimolar ratio. Mechanistic study revealed that the charge pair in the zwitterion works synergistically in activating both NBS and carboxylic acid.
W.-H. Ng, R.-B. Hu, Y.-P. Lam, Y.-Y. Yeung, Org. Lett., 2020, 22, 5567-5571.
A new procedure for aminobromination of olefins gives vicinal bromoamine derivatives in high yields using Cu, Mn, or V catalysts with p-toluenesulfonamide as nitrogen source and N-bromosuccinimide (NBS) as bromine source. Excellent regio- and stereoselectivity is shown for different olefinic substrates as well as transition metal catalysts.
V. V. Thakur, S. K. Talluri, A. Sudalai, Org. Lett., 2003, 5, 861-864.
A convenient and efficient iron-catalyzed aminobromination of alkenes has been developed using inexpensive FeCl2 as the catalyst, amides/sulfonamides and NBS as the nitrogen and bromine sources, respectively, under mild conditions.
Z. Wang, Y. Zhang, H. Fu, Y. Jiang, Y. Zhao, Synlett, 2008, 2667-2668.
In an efficient, catalyst-free, and metal-free bromoamidation of unactivated olefins, 4-(trifluoromethyl)benzenesulfonamide and N-bromosuccinimide were used as the nitrogen and halogen sources, respectively. The methodology is applicable to both cyclic and aliphatic olefins.
W. Z. Yu, F. Chen, Y. A. Cheng, Y.-Y. Yeung, J. Org. Chem., 2015, 80, 2815-2821.
An efficient catalyst-free radical cross-coupling reaction between aromatic aldehydes and sulfoximines took place in the presence of N-bromosuccinimide as the radical initiator under microwave irradiation to afford the corresponding acylated sulfoximines in good yields.
K. K. Rajbongshi, S. Ambala, T. Govender, H. G. Kruger, P. I. Arvidsson, T. Naicker, Synthesis, 2020, 52, 1279-1286.
A novel electrophilic one-pot reaction of an olefin, a cyanimide, an amine, and N-bromosuccinimide enables the synthesis of a number of guanidine derivatives with very good yields - including an rTRTVI precursor.
L. Zhou, J. Chen, J. Zhou, Y.-Y. Yeung, Org. Lett., 2011, 13, 5804-5807.
A stereoselective arylation and vinylation of alkenes without transition-metal catalysts takes place through an interesting NBS-promoted semipinacol rearrangement under mild conditions and a subsequent unusual NaOH-mediated Grob fragmentation.
D.-Y. Yuan, Y.-Q. Tu, C.-A. Fan, J. Org. Chem., 2008, 73, 7797-7799.
A novel cationic Br initiated one-pot synthesis using olefin, nitrile, amine, and N-bromosuccinimide gives imidazolines in good yields. The olefinic substrates and the nitrile partners can be flexibly varied to achieve a range of imidazoline derivatives.
L. Zhou, J. Zhou, C. K. Tan, J. Chen, Y.-Y. Yeung, Org. Lett., 2011, 13, 2448-2451.
A N-bromosuccinimide-mediated direct synthesis of 2,5-diaryloxazoles starting from N-H ketoaziridines proceeds via in situ formation of N-bromoketoaziridines followed by generation of azomethine ylides.
H. S. Samimi, F. Dadvar, Synthesis, 2015, 47, 1899-1904.
3-Oxazoline-4-carboxylates as easily available synthetic intermediates can be oxidized to yield oxazole-4-carboxylates. Furthermore, derivatization of 3-oxazoline-4-carboxylates with Grignard reagents enables a facile preparation of 4-keto-oxazole derivatives.
K. Murai, Y. Takahara, T. Matsushita, H. Komatsu, H. Fujioka, Org. Lett., 2010, 12, 3456-3459.
2-Amino-4-alkyl- and 2-amino-4-arylthiazole-5-carboxylates and their selenazole analogues were synthesized by α-halogenation of β-keto esters with N-bromosuccinimide, followed by cyclization with thiourea or selenourea, respectively, in the presence of β-cyclodextrin in water at 50°C.
M. Narender, M. S. Reddy, V. P. Kumar, B. Srinivas, R. Sridhar, Y. V. D. Nageswar, K. R. Rao, Synthesis, 2007, 3469-3472.
Various 2-aryl-3-arylamino-2-alkenenitriles give N-arylindole-3-carbonitriles in a one-pot manner through NBS- or NCS-mediated halogenation followed by Zn(OAc)2-catalyzed intramolecular cyclization. The process involves the formation of arylnitrenium ion intermediates, which undergo an electrophilic aromatic substitution to give the cyclized N-arylindoles.
Q. Yan, J. Luo, D. Zhang-Negrerie, H. Li, X. Qi, K. Zhao, J. Org. Chem., 2011, 76, 8690-8697.
tert-Butyl sulfoxides can be used as sulfinyl sources in an intramolecular sulfinylation of sulfonamides followed by an all-heteroatom Wittig-equivalent process to afford aryl[4,5]isothiazoles in high yields.
F. Xu, Y. Chen, E. Fan, Z. Sun, Org. Lett., 2016, 18, 2777-2779.
A catalyst-free halogenative cyclization of N-aryl diazoamides with N-halosuccinimides (NXS) provides 3-halooxindoles in good yields through a carbene-free mechanism under mild and catalyst-free conditions. This transformation is proposed to proceed through diazonium ion formation followed by intramolecular Friedel-Crafts alkylation.
C. Ma, D. Xing, W. Hu, Org. Lett., 2016, 18, 3134-3137.
New methodology for the synthesis of variously substituted 2-oxazolines and one dihydrooxazine using aldehydes, amino alcohols, and N-bromosuccinimide as an oxidizing agent is described. This one-pot synthesis is characterized by mild reaction conditions, broad scope, high yields, and its preparative simplicity.
K. Schwekendiek, F. Glorius, Synthesis, 2006, 2996-3002.
A gold-catalyzed cyclization of β-amino-ynone intermediates and halodeauration process enables a rapid and efficient one-step halopyridone synthesis.
K. H. Nguyen, S. Tomasi, M. Le Roch, L. Toupet, J. Renault, P. Uriac, N. Gouault, J. Org. Chem., 2013, 78, 7809-7815.
A versatile and highly efficient Zn(OTf)2-catalyzed one-pot reaction of alkenes, NBS, nitriles, and TMSN3 gives various 1,5-disubstituted tetrazoles containing an additional α-bromo functionality of the N1-alkyl substituent.
S. Hajra, D. Sinha, M. Bhowmick, J. Org. Chem., 2007, 72, 1852-1855.
A one-pot synthesis of aryl sulfones from primary alcohols is described. Alcohols were treated with N-bromosuccinimide and triphenylphosphine, followed by addition of sodium arenesulfinate with a catalytic amount of tetrabutylammonium iodide to afford the aryl sulfones in good to high yields.
T. Murakami, K. Furusawa, Synthesis, 2002, 479-482.
Sulfoxides bearing a tert-butyl group can be activated using N-bromosuccinimide (NBS) under acidic conditions. Subsequent treatment with various nitrogen, carbon, or oxygen nucleophiles affords a wide range of sulfinic acid amides, new sulfoxides, and sulfinic acid esters.
J. Wei, Z. Sun, Org. Lett., 2015, 17, 5396-5399.
Cyanide mediates an in situ generation of a nucleophilic sulfinate ion from vinyl sulfones. Subsequent in situ S-alkylation provides sulfones in high yields. In the presence of N-bromosuccinimide, primary and secondary amines underwent sulfonamide formation.
T. Roy, J.-W. Lee, Synlett, 2020, 31, 455-458.
Thiosulfonates synthesized by copper-catalyzed aerobic dimerization serve as substrate for simple and high-yielding strategies for the production of a variety of sulfones and sulfonamides. Thiosulfinates are stable, nontoxic alternatives to metal sulfinate salts derived from toxic SO2.
P. K. Shyam, H.-Y. Jang, J. Org. Chem., 2017, 82, 1761-1767.
The synthesis of N-cyanosulfilimines can readily be achieved by reaction of the corresponding sulfides with cyanogen amine in the presence of a base and NBS or I2 as halogenating agents. Oxidation followed by decyanation affords synthetically useful sulfoximines.
O. García Mancheño, O. Bistri, C. Bolm, Org. Lett., 2007, 9, 3809-3811.
In a one-pot cascade transformation of ketones into α-imidoketones, N-bromosuccinimide (NBS) provides both electrophilic bromine and nucleophilic nitrogen sources, and diazabicyclo[5.4.1]undec-7-ene (DBU) functions as a base and a nucleophilic promoter for the activation of NBS. α-Bromination is supposed as the key step in the process.
Y. Wei, S. Lin, F. Liang, Org. Lett., 2012, 14, 4202-4205.