N-Chlorosuccinimide (NCS) is a chlorinating and oxidizing agent that is used as source for chlorine in radical reactions and various electrophilic additions.
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.
A mild, efficient, Cu(I)-catalyzed method for the synthesis of aryl chlorides from arylboronic acids is particularly useful for the conversion of electron-deficient arylboronic acids to aryl chlorides, a transformation that is inefficient in the absence of Cu catalysis.
H. Wu, J. Hynes, Jr., Org. Lett., 2010, 12, 1192-1195.
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 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.
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 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.
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.
Using an efficient visible-light photocatalysis-based method, a mixture of an aldehyde, tert-butyl hydrogen peroxide, and N-chlorosuccinimide afforded an acid chloride in the presence of Ru(bpy)3Cl2 as photocatalyst. A subsequent reaction with an amine provided the corresponding amide.
N. Iqbal, E. J. Cho, J. Org. Chem., 2016, 81, 1905-1911.
An operationally simple oxidation-cyanation enables the synthesis of cyanamides using inexpensive and commercially available N-chlorosuccinimide and Zn(CN)2 as reagents. The method avoids the direct handling of toxic cyanogen halides and is amenable for the cyanation of various primary and secondary amines and aniline derivatives.
N. Kuhl, S. Raval, R. D. Cohen, Org. Lett., 2019, 21, 1268-1272.
Treatment of anilines with N-chlorosuccinimide and 1,8-diazabicyclo[5.4.0]undec-7-ene enables a convenient one-step procedure for the synthesis of symmetrical azobenzenes in good yields in minutes.
A. A. John, Q. Lin, J. Org. Chem., 2017, 82, 9873-9876.
An intramolecular chloroamination of allenes with N-chlorosuccinimide proceeds under mild conditions in the presence of a 1,10-phenanthroline-ligated cationic silver complex and 2,6-lutidine as a base. The reaction tolerates various functional groups. The chloroamination products are useful synthetic intermediates and can be easily transformed into functionalized 3-pyrroline and pyrrole derivatives.
M. Sai, S. Matsubara, Org. Lett., 2011, 13, 4676-4679.
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.
A one-pot, cascade reaction sequence of α-azido acrylates and aromatic oximes provides an efficient, straightforward and metal-free synthesis of 3,4,5-trisubstituted isoxazoles under mild reaction conditions via a 1,3-dipolar cycloaddition.
M. Hu, X. He, Z. Niu, Z. Yan, F. Zhou, Y. Shang, Synthesis, 2014, 46, 510-514.
A divergent and regioselective synthesis of either 3-substituted benzisoxazoles or 2-substituted benzoxazoles from readily accessible ortho-hydroxyaryl N-H ketimines proceeds in two distinct pathways through a common N-Cl imine intermediate: (a) N-O bond formation to form benzisoxazole under anhydrous conditions and (b) NaOCl mediated Beckmann-type rearrangement to form benzoxazole, respectively.
C.-y Chen, T. Andreani, H. Li, Org. Lett., 2011, 13, 6300-6303.
A fluorous (S)-pyrrolidine-thiourea bifunctional organocatalyst shows good activity and enantioselectivity for direct α-chlorination of aldehydes using N-chlorosuccinimide (NCS) as the chlorine source. The catalyst can be recovered from the reaction mixture by fluorous solid-phase extraction with excellent purity for direct reuse.
L. Wang, C. Cai, D. P. Curran, W. Zhang, Synlett, 2010, 433-436.
A direct organocatalytic enantioselective α-chlorination of aldehydes proceeds for a series of different aldehydes with NCS as the chlorine source using easily available catalysts such as L-proline amide and (2R,5R)-diphenylpyrrolidine. The α-chloro aldehydes are obtained in very good yield and high enantioselectivity.
N. Halland, A. Braunton, S. Bachmann, M. Marigo, K. A. Jorgensen, J. Am. Chem. Soc., 2004, 126, 4790-4791.
A Rh(III)-catalyzed cascade arylation and chlorination of α-diazocarbonyl compounds with arylboronic acids and N-chlorosuccinimide exhibits excellent functional group tolerance on the organoboron and the diazo reagents. Functionalized α-aryl-α-chlorocarbonyl compounds were obtained in good yields.
F.-N. Ng, Y.-F. Lau, Z. Zhou, W.-Y. Yu, Org. Lett., 2015, 17, 1676-1679.
The use of diphenyl selenide as a Lewis base catalyst enables a mild chloroamidation of a wide rand of olefinic substrates including starting materials with acid labile functional groups.
D. W. Tay, I. T. Tsoi, J. C. Er, G. Y. C. Leung, Y.-Y. Yeung, Org. Lett., 2013, 15, 1310-1313.
Structurally diverse sulfonyl chlorides were synthesized via N-chlorosuccinimide chlorosulfonation in good yields from S-alkylisothiourea salts, which can be easily prepared from readily accessible alkyl halides or mesylates and inexpensive thiourea. In large-scale syntheses, the water-soluble byproduct succinimide can be conveniently converted into the starting reagent N-chlorosuccinimide with sodium hypochlorite.
Z. Yang, J. Xu, Synthesis, 2013, 45, 1675-1682.
A smooth oxidation of several thiol derivatives by a combination of N-chlorosuccinimide and dilute hydrochloric acid afforded the corresponding sulfonyl chlorides in good yield.
A. Nishiguchi, K. Maeda, S. Miki, Synthesis, 2006, 4131-4134.
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 method for the synthesis of N-aroylated sulfoximines involves a manganese oxide promoted C-H activation of methyl arenes to form an aroyl intermediate which then reacts readily with N-chlorosulfoximines to form a series of valuable aroyl sulfoximine derivatives in high yields.
D. L. Priebbenow, C. Bolm, Org. Lett., 2014, 16, 1650-1652.