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

Tapanee Maibunkaew; Charnsak Thongsornkleeb; Jumreang Tummatorn; Anon Bunrit; Somsak Ruchirawat

doi:10.1055/s-0034-1378225

Synlett, Table of Contents

Synlett 2014; 25(12): 1769-1775
DOI: 10.1055/s-0034-1378225

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

Tapanee Maibunkaew

^aProgram 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*

^aProgram 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

^bChulabhorn Research Institute, 54 Kampang Phet 6, Laksi, Bangkok 10210, Thailand Fax: +66(2)5538545 Email: charnsak@cri.or.th

,

Jumreang Tummatorn

^bChulabhorn Research Institute, 54 Kampang Phet 6, Laksi, Bangkok 10210, Thailand Fax: +66(2)5538545 Email: charnsak@cri.or.th

,

Anon Bunrit

^bChulabhorn Research Institute, 54 Kampang Phet 6, Laksi, Bangkok 10210, Thailand Fax: +66(2)5538545 Email: charnsak@cri.or.th

,

Somsak Ruchirawat

^aProgram 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

^bChulabhorn Research Institute, 54 Kampang Phet 6, Laksi, Bangkok 10210, Thailand Fax: +66(2)5538545 Email: charnsak@cri.or.th

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Abstract

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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.

Key words

interhalogens - electrophilic aromatic halogenation - isocryptolepine - chlorotrimethylsilane - N-halosuccinimide

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References

References and Notes

1a Davis SG In Organotransition Metal Chemistry: Applications to Organic Synthesis. Pergamon Press; Oxford, UK: 1982
1b Cannon KC, Krow GR In Handbook of Grignard Reagents . Dekker; New York: 1996

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

Supplementary Material

Supporting Information

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

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