Categories: N-S Bond Formation >
Synthesis of sulfonamides
An easy and handy synthesis of sulfonamides directly from sulfonic acids or its sodium salts is performed under microwave irradiation, has shown a good functional group tolerance, and is high yielding.
L. De Luca, G. Giacomelli, J. Org. Chem., 2008, 73, 3967-3969.
The combination of H2O2 and SOCl2 is a highly reactive reagent for the direct oxidative conversion of thiol derivatives to the corresponding sulfonyl chlorides through oxidative chlorination. Upon reaction with amines, the corresponding sulfonamides were obtained in excellent yields in very short reaction times.
K. Bahrami, M. M. Khodaei, M. Soheilizad, J. Org. Chem., 2009, 74, 9287-9291.
In situ preparation of sulfonyl chlorides from thiols by oxidation with N-chlorosuccinimide (NCS), tetrabutylammonium chloride, and water followed by reaction with amine or sodium azide in the same reaction vessel enables a convenient synthesis of sulfonamides and sulfonyl azides.
H. Veisi, R. Ghorbani-Vaghei, S. Hemmati, J. Mahmoodi, Synlett, 2011, 2315-2320.
A mild and efficient reaction of amine derived sulfonate salts in the presence of cyanuric chloride, triethylamine as base, and anhydrous acetonitrile as solvent at room temperature gives the corresponding sulfonamides in good to excellent yields.
M. N. S. Rad, A. Khalafi-Nezhad, Z. Asrari, S. Behrouz, Z. Amini, M. Behrouz, Synthesis, 2009, 3983-3988.
The combination of calcium triflimide and DABCO activates sulfamoyl fluorides, fluorosulfates, and sulfonyl fluorides for SuFEx with amines to provide a diverse set of sulfamides, sulfamates, and sulfonamides at room temperature under mild conditions.
S. Mahapatra, C. P. Woroch, T. W. Butler, S. N. Carneiro, S. C. Kwan, S. R. Khasnavis, J. Gu, J. K. Dutra, B. C. Vetelino, J. Bellenger, C. W. am Ende, N. D. Ball, Org. Lett., 2020, 22, 4389-4394.
Calcium triflimide [Ca(NTf2)2] as a Lewis acid activates a wide array of sterically and electronically diverse sulfonyl fluorides toward nucleophilic addition with amines to provide the corresponding sulfonamides in good yield.
P. Mukherjee , C. P. Woroch, L. Cleary, M. Rusznak, R. W. Franzese, M. R. Reese, J. W. Tucker, J. M. Humphrey, S. M. Etuk, S. C. Kwan, C. W. am Ende, N. D. Ball, Org. Lett., 2018, 20, 3943-3947.
Heterocyclic thioethers and sulfones serve as readily available precursors for a convenient synthesis of α-chiral sulfinates. Treatment of the sulfinates with hydroxylamine sulfonate in aqueous solution provides α-C-chiral primary sulfonamides in good yield with retention of stereochemical purity.
M. G. Johson, M. W. Gribble Jr., J. B. Houze, N. A. Paras, Org. Lett., 2014, 16, 6248-6251.
A stereoretentive approach to sp3-enriched secondary sulfonamides bearing an asymmetric center at the α position to the sulfur atom relies on the electrophilic amination of the corresponding stereochemically pure sulfinates with N-alkylhydroxylamine sulfonic acids. This convenient method tolerates several functional groups (e.g., ether, phthalimide, or N-Boc carbamate).
V. A. Andriashvili, S. Zhersh, A. A. Tolmachev, O. O. Grygorenko, J. Org. Chem., 2022, 87, 6237-6246.
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.
A facile and efficient indium-catalyzed sulfonylation of amines allows the synthesis of a wide range of sulfonamides in excellent yields. The method showed a generality for substrates including less nucleophilic and sterically hindered anilines, and it is also applicable for preparing sulfonic esters from sulfonyl chlorides and alcohols.
J. Yan, J. Li, D. Cheng, Synlett, 2007, 2442-2444.
A one-pot three-component reaction involving nitroarenes, (hetero)arylboronic acids, and potassium pyrosulfite provides a broad range of sulfonamides bearing different reactive functional groups in very good yields through sequential C-S and S-N coupling.
K. Chen, W. Chen, B. Han, W. Chen, M. Liu, H. Wu, Org. Lett., 2020, 22, 1841-1845.
A synthesis of N-arylsulfonamides from readily available nitroarenes and sodium arylsulfinates was realized in the presence of FeCl2 as catalyst and NaHSO3 as reductant under mild conditions. A broad range of functional groups were tolerated. Mechanistic studies indicated that the N-S bond might be generated through direct coupling of nitroarene with sodium arylsulfinate prior to the reduction.
W. Zhang, J. Xie, B. Rao, M. Luo, J. Org. Chem., 2015, 80, 3504-3511.
A simple copper-catalyzed aminosulfonylation of aryldiazonium tetrafluoroborates, DABCO·(SO2)2, and N-chloroamines provides a wide range of sulfonamides in good yields under mild conditions. Mechanistic investigation suggests that a radical process and transition-metal catalysis take place.
F. Zhang, D. Zheng, L. Lai, J. Cheng, J. Sun, J. Wu, Org. Lett., 2018, 20, 1167-1170.
A Pd-catalyzed coupling of aryl iodides and the sulfur dioxide surrogate DABSO provides aryl ammonium sulfinates, that can be transformed in a one-pot process to various functionalized sulfonamides by simple treatment with an aqueous solution of the relevant amine and sodium hypochlorite (bleach). A broad range of amines, including anilines, and amino acid derivatives can be used.
E. F. Flegeau, J. M. Harrison, M. C. Willis, Synlett, 2016, 27, 101-105.
The bench-stable colorless solid charge-transfer complex generated from the combination of DABCO and sulfur dioxide, DABSO, can replace gaseous sulfur dioxide in organic synthesis. Reactions with Grignard reagents form sulfinates, which can then be converted in situ to sulfonamides. Alternatively, reaction with anilines and iodine leads to the formation of a series of sulfamides.
H. Woolven, C. Gonzáles-Rodríguez, I. Marco, A. L. Thompson, M. C. Willis, Org. Lett., 2011, 13, 4876-4878.
In ionic liquids [Bmim][PF6] or [Bmim][BF4], a highly regioselective N-substitution of pyrrole with alkyl halides, sulfonyl chlorides, and benzoyl chloride gave substituted pyrroles in excellent yields. Michael addition of pyrrole with electrophilic olefins was completed in a highly regioselective manner to afford N-alkylpyrroles.
Z.-G. Lea, Z.-C. Chen, Y. Hu, Q.-G. Zheng, Synthesis, 2004, 1951-1954.