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Unformatted text preview: 641 AMINES OCH3 OCH3 OCH3
NH2 N 1. NaNO2, HCl, H2O N F
BF4 2. HBF4 o-Anisidine (c) heat o-Methoxybenzenediazonium
fluoroborate (57%) o-Fluoroanisole
(53%) We can use the o-ﬂuoroanisole prepared in part (b) to prepare 3-ﬂuoro-4-methoxyacetophenone by Friedel–Crafts acylation.
as in part (b) OCH3 OO F CH3COCCH3
o-Anisidine (d ) o-Fluoroanisole CCH3 3-Fluoro-4-methoxyacetophenone
(70–80%) Remember from Section 12.16 that it is the more activating substituent that determines the
regioselectivity of electrophilic aromatic substitution when an arene bears two different substituents. Methoxy is a strongly activating substituent; ﬂuorine is slightly deactivating.
Friedel–Crafts acylation takes place at the position para to the methoxy group.
The o-ﬂuoroanisole prepared in part (b) serves nicely as a precursor to 3-ﬂuoro-4-methoxybenzonitrile via diazonium salt chemistry.
F OCH3 NH2 CN OCH3
F F F [from part (b)] NO2 The desired sequence of reactions to carry out the synthesis is
F HNO3 as in part (b) F H2, Pt NO2
o-Anisidine o-Fluoroanisole NH2 2-Fluoro-4nitroanisole
(85%) 1. NaNO2, HCl, H2O
2. CuCN OCH3
3-Fluoro-4methoxybenzonitrile (46%) Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website ...
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