Categories: C-Br Bond Formation >
Synthesis of aryl bromides
Mandelic acid catalyzes a highly regioselective aromatic bromination with N-bromosuccinimide (NBS) under aqueous conditions at room temperature. Computational results demonstrate that Lewis basic additives interact with NBS to increase the electropositive character of bromine prior to electrophilic transfer.
S. I. Baker, M. Yaghoubi, S. L. Bidwell, S. L. Pierce, H. P. Hratchian, R. D. Baxter, J. Org. Chem., 2022, 87, 8492-8502.
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.
DMSO as a mild and inexpensive oxidant enables an efficient and practical bromination and iodination of arenes with HX (X = Br, I) reagents. This oxidative system is amenable to late-stage bromination of natural products and kilogram-scale conversions.
S. Song, X. Sun, X. Li, Y. Yuan, N. Jiao, Org. Lett., 2015, 17, 2886-2889.
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 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.
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.
Moderately deactivated arenes are efficiently brominated with 0.34 eq. tribromoisocyanuric acid in trifluoroacetic acid at room temperature. The use of trifluoroacetic acid avoids the polybromination of the substrate, as can be observed in the same reaction performed in 98% H2SO4.
L. S. de Almeida, M. C. S. de Mattos, P. M. Esteves, Synlett, 2013, 24, 603-606.
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.
Vanadium pentoxide very effectively promotes the bromination of organic substrates, including selective bromination of some aromatics, by tetrabutylammonium bromide in the presence of hydrogen peroxide. The reaction offers mild conditions, high selectivity, yield, and reaction rate, and redundancy of bromine and hydrobromic acid.
U. Bora, G. Bose, M. K. Chaudhuri, S. S. Dhar, R. Gopinath, A. T. Khan, B. K. Patel, Org. Lett., 2000, 2, 247-249.
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.
A highly efficient, rapid and regioselective protocol for the ring bromination of aromatic compounds under mild conditions can be conducted with ammonium bromide as a source of bromine source and Oxone as an oxidant. Various aromatic compounds reacted smoothly to give the corresponding monobrominated products in good yields in very short reaction times.
N. Naresh, M. A. Kumar, M. M. Reddy, P. Swamy, J. B. Nanubolu, N. Narender, Synthesis, 2013, 45, 1497-1504.
A simple, efficient and mild method for the selective bromination of activated aromatic compounds using ammonium bromide as the source of bromine and Oxone as the oxidant in methanol or water as solvent proceeds at ambient temperature in good yields without a catalyst.
M. A. Kumar, C. N. Rohitha, S. J. Kulkarni, N. Narender, Synthesis, 2010, 1629-1632.
Iodobenzene can be used as a recyclable catalyst in combination with m-chloroperbenzoic acid as the terminal oxidant for an efficient and regioselective monobromination of electron-rich aromatic compounds. The bromination of electron-rich aromatic compounds with lithium bromide was fast in tetrahydrofuran at room temperature, providing regioselective monobrominated products in good yields.
Z. Zhou, X. He, Synthesis, 2011, 207-209.
A catalytic decarboxylative halogenation of (hetero)aryl carboxylic acids accommodates an exceptionally broad scope of substrates. The generated aryl radical intermediate enables divergent functionalization pathways: (1) atom transfer to access bromo- or iodo(hetero)arenes or (2) radical capture by copper and subsequent reductive elimination to generate chloro- or fluoro(hetero)arenes.
T. Q. Chen, P. Scott Pedersen, N. W. Dow, R. Fayad, C. E. Hauke, M. S. Rosko, E. O. Danilov, D. C. Blakemore, A.-M. Dechert-Schmitt, T. Knauber, F. N. Castelano, D. W. C. MacMillan, J. Am. Chem. Soc., 2022, 144, 8296-8305.
AuCl3-catalyzed halogenations of aryl borononates with N-halosuccinimides enables a convenient synthesis of aromatic boronates bearing halogen substituents in the aromatic ring.
D. Qiu, F. Mo, Z. Zheng, Y. Zhang, J. Wang, Org. Lett., 2010, 12, 5474-5477.
N,N,N',N'-Tetrabromobenzene-1,3-disulfonylamide (TBBDA) and poly[N-bromobenzene-1,3-disulfonylamide] (PBBS) can be used for the regioselective bromination of aromatic compounds in excellent yields under mild conditions.
R. Ghorbani-Vaghei, H. Jalili, Synthesis, 2005, 1099-1102.
Organotrifluoroborates are rapidly and regioselectively converted into organic bromides in excellent yields under mild conditions, using sodium bromide in the presence of chloramine-T.
G. W. Kabalka, A. R. Mereddy, Organometallics, 2004, 23, 4519-4521.
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.
ridium-catalyzed borylation of 1,3-disubstituted arenes with B2pin2, followed by reaction of the boronic ester with copper(II) bromide or chloride converts arylboronic esters to the corresponding meta-halogenated aryl halides. Various functional groups, such as alkoxy, alkyl, halogen, nitrile, ester, amide, and pivaloyl and TIPS-protected alcohols, are tolerated.
J. M. Murphy, X. Liao, J. F. Hartwig, J. Am. Chem. Soc., 2007, 129, 15434-15435.
Mild, novel procedures have been developed for the syntheses of aryl halides from the corresponding phenols in modest to good yields via boronate ester intermediates.
A. L. S. Thompson, G. W. Kabalka, M. R. Akula, J. W. Huffman, Synthesis, 2005, 547-550.
Aryl triflates were simply transformed to aryl bromides or iodides in the presence of LiBr or NaI and [Cp*Ru(MeCN)3]OTf as catalyst. A similar transformation of alkenyl sulfonates and phosphates can be conducted under mild conditions to provide the corresponding halides.
Y. Imazaki, E. Shirakawa, R. Ueno, T. Hayashi, J. Am. Chem. Soc., 2012, 134, 14760-14761.
A facile Pd-catalyzed conversion of aryl and vinyl triflates allows convenient access to various aryl, heteroaryl, and vinyl halides in good to excellent yields and with greatly simplified conditions relative to our previous report.
J. Pan, X. Wang, Y. Zhang, S. L. Buchwald, Org. Lett., 2011, 13, 4974-4976.
An efficient version of the Sandmeyer bromination using catalytic amounts of Cu(I)/Cu(II)/phen is highly useful for the preparation of various aryl bromides and dibromides in excellent yields.
I. P. Beletskaya, A. S. Sigeev, A. S. Peregudov, P. V. Petrovskii, Synthesis, 2007, 2534-2538.
Halogen abstraction from bromotrichloromethane and diiodomethane enables a metal-free synthesis of aryl bromides and iodides from anilines without isolation of diazonium salts. The transformation offers short reaction times, a simple workup, and insensitivity to moisture and air and avoids excess halogenation. This method represents a convenient alternative to the classic Sandmeyer reaction.
D. A. Leas, Y. Dong, J. L. Vennerstrom, D. E. Stack, Org. Lett., 2017, 19, 2518-2521.
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.
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.
Silver carbonate or nickel(II) chloride catalyzes an ortho-C-H bond halogenation of anilides and N-aryl carbamates with N-halosuccinimides to provide 2-haloanilides and carbamates, which may serve as starting materials for the synthesis of pharmaceutically and biologically active compounds.
E. Kianmehr, H. Afaridoun, Synthesis, 2021, 53, 1513-1523.
A standard ortho-lithiation/bromination procedure applied to bromoarenes resulted in poor yields of the corresponding 1,2-dibromoarenes. Transmetalation of the aryllithium intermediates with ZnCl2, followed by bromination, improved the yields of the synthetically useful 1,2-dibromoarenes dramatically.
K. Menzel, E. L. Fisher, L. DiMichele, D. E. Frantz, T. D. Nelson, M. H. Kress, J. Org. Chem., 2006, 71, 2188-2191.
A mild palladium-catalyzed, regioselective chlorination, bromination, and iodination of arene C-H bonds using N-halosuccinimides as oxidants is described. These transformations can provide products that are complementary to those obtained via conventional electrophilic aromatic substitution reactions.
D. Kalyani, A. R. Dick, W. Q. Anani, M. S. Sanford, Org. Lett., 2006, 8, 2523-2526
Use of a solvent with greater density than the fluorous phase is an alternative to the U-tube method in phase-vanishing reactions in cases where both reactants are less dense than the fluorous phase.
N. K. Jana, J. G. Verkade, Org. Lett., 2003, 5, 3787-3790.