2,4,6-Trichlorobenzoyl Chloride (Yamaguchi Reagent)

Dedicated to my beloved parents and my research supervisor Dr. Asish K. Bhattacharya.

Introduction

2,4,6-Trichlorobenzoyl chloride (TCBC), known as ­Yamaguchi reagent, is widely used for the Yamaguchi esterification. Yamaguchi and co-workers were the first to discover its use as esterifying reagent in 1979.[1] It is a light yellow colored liquid (bp 107–108 °C, ρ = 1.561 g/cm³)[2] and a moisture-sensitive reagent.

TCBC allows the regioselective synthesis of highly functionalized esters under mild reaction conditions. The ­Yamaguchi esterification is one of the most preferred protocol for macrolactonizations as evident by more than 340 research papers published using this methodology.[3]

• References

• 1a Inanaga J, Hirata K, Saeki H, Katsuki T, Yamaguchi M. Bull. Chem. Soc. Jpn. 1979; 52: 1989
• 1b Kawanami Y, Dainobu Y, Inanaga J, Katsuki T, Yamaguchi M. Bull. Chem. Soc. Jpn. 1981; 54: 943
• 2 Ewin R. A., Pertusati F. 2013. 2,4,6-Trichlorobenzoyl Chloride. e-EROS Encyclopedia of Reagents for Organic Synthesis.
• 3 Parenty A, Moreau X, Niel G, Campagne J.-M. Chem. Rev. 2013; 113: PR1
• 4 Inanaga J, Katsuki T, Takimoto S, Ouchida S, Inoue K, Nakano A, Okukado N, Yamaguchi M. Chem. Lett. 1979; 1021
• 5 Sutter MA, Seebach D. Liebigs Ann. Chem. 1983; 939
• 6 Robinson A, Aggarwal VK. Angew. Chem. Int. Ed. 2010; 49: 6673
• 7 Valot G, Regens CS, O’Malley DP, Godineau E, Takikawa H, Fürstner A. Angew. Chem. Int. Ed. 2013; 52: 9534
• 8 McGowan MA, Stevenson CP, Schiffler MA, Jacobsen EN. Angew. Chem. Int. Ed. 2010; 49: 6147
• 9 Lisboa MP, Jones DM, Dudley GB. Org. Lett. 2013; 15: 886
• 10 Waldmann H, Kunz H. J. Org. Chem. 1988; 53: 4172
• 11 Glorius F, Grohmann C, Wang H. Org. Lett. 2013; 15: 3014