Synlett 2014; 25(12): 1769-1775
DOI: 10.1055/s-0034-1378225
letter
© Georg Thieme Verlag Stuttgart · New York

Practical and Metal-Free Electrophilic Aromatic Halogenation by Inter­halogen Compounds Generated In Situ from N-Halosuccinimide and Catalytic TMSCl

Tapanee Maibunkaew
a  Program on Chemical Biology, Chulabhorn Graduate Institute, Center of Excellence on Environmental Health and Toxicology, CHE, Ministry of Education, 54 Kampang Phet 6, Laksi, Bangkok 10210, Thailand
,
Charnsak Thongsornkleeb*
a  Program on Chemical Biology, Chulabhorn Graduate Institute, Center of Excellence on Environmental Health and Toxicology, CHE, Ministry of Education, 54 Kampang Phet 6, Laksi, Bangkok 10210, Thailand
b  Chulabhorn Research Institute, 54 Kampang Phet 6, Laksi, Bangkok 10210, Thailand   Fax: +66(2)5538545   Email: charnsak@cri.or.th
,
Jumreang Tummatorn
b  Chulabhorn Research Institute, 54 Kampang Phet 6, Laksi, Bangkok 10210, Thailand   Fax: +66(2)5538545   Email: charnsak@cri.or.th
,
Anon Bunrit
b  Chulabhorn Research Institute, 54 Kampang Phet 6, Laksi, Bangkok 10210, Thailand   Fax: +66(2)5538545   Email: charnsak@cri.or.th
,
Somsak Ruchirawat
a  Program on Chemical Biology, Chulabhorn Graduate Institute, Center of Excellence on Environmental Health and Toxicology, CHE, Ministry of Education, 54 Kampang Phet 6, Laksi, Bangkok 10210, Thailand
b  Chulabhorn Research Institute, 54 Kampang Phet 6, Laksi, Bangkok 10210, Thailand   Fax: +66(2)5538545   Email: charnsak@cri.or.th
› Author Affiliations
Further Information

Publication History

Received: 28 March 2014

Accepted after revision: 01 May 2014

Publication Date:
05 June 2014 (online)


Abstract

Halomonochloride compounds (ClCl, BrCl, ICl) generated in situ from N-halosuccinimide and catalytic chlorotrimethylsilane (TMSCl, 0.1 equiv) can efficiently halogenate aromatic compounds to give halogenated products in good to excellent yields and selectivities. The reaction can be carried out at room temperature or at lower temperatures, requires only one hour, is practical to apply to a wide range of substrates, and provides a simple access to a variety of haloarene compounds.

Supporting Information

 
  • References and Notes

    • 2a Miyaura N, Suzuki A. Chem. Rev. 1995; 95: 2457
    • 2b Beletskaya IP, Cheprakov AV. Chem. Rev. 2000; 100: 3009
    • 2c Meijere A, Meyer FE. Angew. Chem., Int. Ed. 1994; 33: 2379
  • 3 Hernandes MZ, Cavalcanti SM. T, Moreira DR. M, de Azevedo JrW. F, Leite AC. L. Curr. Drug Targets 2010; 11: 303
  • 4 Kamigata N, Satoh T, Yoshida M, Matsuyama H, Kameyama M. Bull. Chem. Soc. Jpn. 1988; 61: 2226
    • 5a Zhang Y, Shibatomi K, Yamamoto H. Synlett 2005; 2837
    • 5b Zhang Y, Yamamoto H. Eur. Patent 1928599B1, 2006
    • 6a Mo F, Yan JM, Qiu D, Li F, Zhang Y, Wang J. Angew. Chem. Int. Ed. 2010; 49: 2028
    • 6b Qiu D, Mo F, Zheng Z, Zhang Y, Wang J. Org. Lett. 2010; 12: 5474
  • 7 Tanemura K, Suzuki T, Nishida Y, Satsumabayashi K, Horaguchi T. Chem. Lett. 2003; 32: 932
  • 8 Castanet A.-S, Colobert F, Broutin P.-E. Tetrahedron Lett. 2002; 43: 5047
  • 9 Yu G, Mason HJ, Wu X, Endo M, Douglas J, Macora JE. Tetrahedron Lett. 2001; 42: 3247
  • 10 Bovonsombat P, Ali R, Khan C, Leykajarakul J, Pla-on K, Aphimanchindakul S, Pungcharoenpong N, Timsuea N, Arunrat A, Punpongjareorn N. Tetrahedron 2010; 66: 6928
  • 11 Goldberg Y, Alper H. J. Org. Chem. 1993; 58: 3072
  • 12 Schmid H. Helv. Chim. Acta 1946; 29: 1144
  • 13 Shao L.-X, Shi M. Synlett 2006; 1269
  • 14 Mahajan T, Kumar L, Dwivedi K, Agarwal DD. Ind. Eng. Chem. Res. 2012; 51: 3881
  • 15 Bunrit A, Ruchirawat S, Thongsornkleeb C. Tetrahedron Lett. 2011; 52: 3124
  • 16 Tummatorn J, Thongsornkleeb C, Ruchirawat S. Tetrahedron 2012; 68: 4732
    • 17a Sharaf MH. M, Schiff JrP. L, Tackie AN, Phoebe JrC. H, Martin GE. J. Heterocycl. Chem. 1996; 33: 239
    • 17b Cimanga K, De Bruyne T, Pieters L, Claeys M, Vlietinck A. Tetrahedron Lett. 1996; 37: 1703
    • 17c Grellier P, Ramiaramanana L, Millerioux V, Deharo E, Schrével J, Frapper F, Trigalo F, Bodo B, Pousset J.-L. Phytother. Res. 1996; 10: 317
    • 17d Baelen GV, Hostyn S, Dhooghe L, Tapolcsányi P, Mátyus P, Lemière G, Dommisse R, Kaiser M, Brun R, Cos P, Maes L, Hajós G, Riedl Z, Nagy I, Maes BU. W, Pieters L. Bioorg. Med. Chem. 2009; 17: 7209
    • 17e Whittell LR, Batty KT, Wong RP. M, Bolitho EM, Fox SA, Davis TM. E, Murray PE. Bioorg. Med. Chem. 2011; 19: 7519
  • 18 Thongsornkleeb C, Rabten W, Bunrit A, Tummatorn J, Ruchirawat S. Tetrahedron Lett. 2012; 53: 6615
  • 19 General Procedure for the Electrophilic Aromatic Halogenation; 4-Bromo-2-chloro-1-methoxybenzene (2a-Cl) and 2,4-Dichloro-1-methoxybenzene (2a-diCl; Ref 20): To a solution of 4-bromoanisole (1a; 200.8 mg, 1.09 mmol, 1.0 equiv) in MeCN (2 mL) was added N-chlorosuccinimide (NCS; 158.3 mg, 1.19 mmol, 1.1 equiv) at r.t. to give a slightly cloudy mixture. Chlorotrimethyl-silane (TMSCl; 14 μL, 0.11 mmol, 0.1 equiv) was then added dropwise to the reaction mixture. Within a few minutes, the reaction mixture became clear pale yellow solution. The mixture was stirred continuously at r.t. for 1 h and H2O was added to it. The separated aqueous layer was extracted with EtOAc. The combined organic phases were washed with sat. aq NaCl, dried over Na2SO4 and concentrated. The crude material was purified by flash SiO2 column eluted with 5–10% EtOAc–hexane to give a mixture of 4-bromo-2-chloro-1-methoxybenzene (2a-Cl) and 2,4-dichloro-1-methoxybenzene (2a-diCl): 237.0 mg yield (88% of 2a-Cl and 11% of 2a-diCl, based on NMR ratio 2a-Cl/2a-diCl = 7.1:1.0; as a pale yellow solid). IR (neat): 2854, 1288, 1222, 1028 cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.49 (d, J = 2.4 Hz, 1 H), 7.36 (d, J = 2.4 Hz, 0.15 H, minor), 7.32 (dd, J = 8.7, 2.4 Hz, 1 H), 7.19 (dd, J = 9.0, 2.7 Hz, 0.14 H, minor), 6.84 (d, J = 8.7 Hz, 0.15 H, minor), 6.79 (d, J = 8.7 Hz, 1 H), 3.87 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 154.4, 132.6, 130.5, 129.9 (minor), 127.6 (minor), 123.6, 113.3, 112.8 (minor), 112.5, 56.34, 56.28 (minor).
  • 20 Garcia P, Lau YY, Perry MR, Schafer LL. Angew. Chem. Int. Ed. 2013; 52: 9144