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Diminished Reactivity of Ortho-Substituted Phenacyl Bromides toward Nucleophilic Displacement

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Chemical Development Department, GlaxoSmithKline Co., 5 Moore Drive, Research Triangle Park, North Carolina 27709 [email protected]
Cite this: J. Org. Chem. 2003, 68, 4, 1594–1596
Publication Date (Web):January 23, 2003
https://doi.org/10.1021/jo011042o
Copyright © 2003 American Chemical Society
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    Abstract

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    A systematic increase of substitution rates by tert-butylamine on α-bromopropiophenones is observed with meta or para substituents with increasing electron-withdrawing ability (k × 103 L M-1 min-1 = 12.7 (p-CH3), 15.7 (o-F), 20.5 (H), 20.0 (p-Cl), 23.6 (m-Cl), 27.3 (p-CF3)). Within an ortho-substituted series, the reactivities decrease (k × 103 L M-1 min-1 = 7.64 (o-OCH3), 5.31 (o-CH3), 2.85 (o-Cl), 2.40 ( o-CF3)). Ortho-substitution results occur from rotational barrier effects and an Aδσ+ Bδσ+ repulsion. The major bonding contribution between reaction and α-substituent centers (A−B) is only the σ bond. When π bonding is allowed between A and B (meta/para-substitution), delocalization and stabilization of the reacting center occurs.

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    1H NMR spectra for the o-propiophenones, selected α-bromo compounds, and mass spectral product characterizations. This material is available free of charge via the Internet at http://pubs.acs.org.

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