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Regioselectivity Differentiation in Metalations of 3,5-Dichloro-Tertiary versus Secondary Benzamides
Department of Chemistry, The College of New Jersey, Ewing, USA
Department of Chemistry, The College of New Jersey, Ewing, USA
Department of Chemistry, The College of New Jersey, Ewing, USA
Department of Chemistry, The College of New Jersey, Ewing, USA
Department of Chemistry, The College of New Jersey, Ewing, USA
Department of Chemistry, The College of New Jersey, Ewing, USA
- 1 Department of Chemistry, The College of New Jersey, Ewing, USA
- 2 Department of Chemistry, The College of New Jersey, Ewing, USA
- 3 Department of Chemistry, The College of New Jersey, Ewing, USA
- 4 Department of Chemistry, The College of New Jersey, Ewing, USA
- 5 Department of Chemistry, The College of New Jersey, Ewing, USA
- 6 Department of Chemistry, The College of New Jersey, Ewing, USA
International Journal of Organic Chemistry·Volume 06 (2016)·Pages 142–146·Published 19 May 2016·DOI10.4236/ijoc.2016.62015
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Abstract
Metalation regioslectivity of 3,5-dichlorobenzamides is a function of the type of amide (secondary versus tertiary) used in the sequence. Metalation at the 2-position (adjacent to the carboxamide functional group) occurs when the secondary benzamide is metalated with sec-butyllithium/ TMEDA mediated through complex-induced proximity effects (CIPE) process, whereas metalation with sec-butyllithium/TMEDA occurs exclusively at the 4-position when the tertiary benzamide is used under identical reaction conditions.
KeywordsDirected Ortho-MetalationComplex-Induced Proximity Effects (CIPE)35-Dichlorobenzamides
- El-Hiti, G.A., Smith, K., Hegazy, A.S., Alshammari, M.B. and Masmali, A.M., ARKIVOC (Gainesville, FL, United States) (2015) For a Comprehensive Recent Review of Directed Ortho-Metalation. 4Spec.Issue, 19-47/1-19-47/30.
- Snieckus, V. (1990) Directed Ortho Metalation. Tertiary Amide and O-Carbamate Directors in Synthetic Strategies for Polysubstituted Aromatics. Chemical Reviews, 90, 879-933. http://dx.doi.org/10.1021/cr00104a001
- Epsztajn, J., Jozwiak, A. and Szczesniak, A.K. (2006) Secondary Amides as Ortho-Directed Metallation Groups for Arenes: A Useful Construction Way of the Polysubstituted Aromatic and Heteroaromatic Systems. Current Organic Chemistry, 10, 1817-1848. http://dx.doi.org/10.2174/138527206778249883
- Beak, P. and Meyers, A.I. (1986) Stereo- and Regiocontrol by Complex Induced Proximity Effects: Reactions of Organolithium Compounds. Accounts of Chemical Research, 19, 356-363. http://dx.doi.org/10.1021/ar00131a005
- Beak, P. and Snieckus, V. (1982) Directed Lithiation of Aromatic Tertiary Amides: An Evolving Synthetic Methodology for Polysubstituted Aromatics. Accounts of Chemical Research, 15, 306-312. http://dx.doi.org/10.1021/ar00082a002
- Schlosser, M. (2005) The 2×3 Toolbox of Organometallic Methods for Regiochemically Exhaustive Functionalization. Angewandte Chemie International Edition, 44, 376-393. http://dx.doi.org/10.1002/anie.200300645
- Campos, K.R. (2007) Direct Sp3 C-H Bond Activation Adjacent to Nitrogen in Heterocycles. Chemical Society Reviews, 36, 1069-1084. http://dx.doi.org/10.1039/B607547A
- Demas, M., Javadi, G.J., Bradley, L.M. and Hunt, D.A. (2000) Metalation of a 3,5-Dichloro-Tertiary Benzamide. An Unusual Regioselectivity Observation. The Journal of Organic Chemistry, 65, 7201-7202. http://dx.doi.org/10.1021/jo000160t
- Marna, C., Whisler, M.C., MacNeil, S., Snieckus, V. and Beak, P. (2004) Angewandte Chemie International Edition, 43, 2206-2225.
- Fraser, R.R., Bresse, M. and Mansour, T.S. (1983) Ortho Lithiation of Monosubstituted Benzenes: A Quantitative Determination of pKa Values in Tetrahydrofuran. Journal of the American Chemical Society, 105, 7790-7791. http://dx.doi.org/10.1021/ja00364a078
- Shatenshtein, A.I. (1962) Mechanism Study of the Protophilic Substitution of Hydrogen in Aromatic Compounds by Means of Hydrogen Isotope Exchange with Liquid Ammonia. Tetrahedron, 18, 95-106. http://dx.doi.org/10.1016/0040-4020(62)80029-5