Abstract
An efficient synthesis of monofluorophenols via the reaction
of difluorobenzene derivatives with potassium trimethylsilanoate
in moderate to excellent yields is described. High regioselectivity
was observed in some cases.
Key words
fluorophenols - synthesis - regioselective - aromatic - substitution
References and Notes
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Typical Procedure
2 -flushed four-necked round-bottom flask (2 L) equipped
with a mechanical stirrer, a condenser, a tem-perature controller,
and a N2 inlet, was added potassium trimethylsilanolate
(225.0 g, 1.75 mole), 1-bromo-3,5-difluorobenzene (1i ,
96.5 g, 0.5 mole), and diglyme (300 mL) under N2 . The
reaction mixture was heated to 120 ˚C for 5 h.
After cooling to r.t., a solution of 1 N HCl (600 mL) was added
slowly. The mixture was then extracted with TBME (1 L). The organic
extract was washed with H2 O (3 × 500 mL), brine
(500 mL), dried over MgSO4 , filtered, and concentrated
in vacuo to give the crude product as a reddish liquid. The crude
material was then distillated to give the pure product 3-bromo-5-fluorophenol
(4i ) as a slightly yellow liquid (88.0
g, 92% yield); bp 52-55 ˚C/1.33˙10-4 bar. ¹ H
NMR (300 MHz, CDCl3 ): δ = 5.634 (s,
1 H), 6.66-6.72 (m, 1 H), 6.78-6.82 (m, 1 H),
7.11-7.23 (m, 1 H).
¹³ C
NMR (75 MHz, CDCl3 ): δ = 98.0 (d, J = 23.0 Hz,
1 C), 108.0 (d, J = 21.8
Hz, 2 C), 111.4 (d, J = 2.9
Hz, 2 C), 128.9 (d, J = 9.5
Hz, 2 C), 153.8 (d, J = 2.7
Hz, 1 C), 159.4 (d, J = 245.6
Hz, 1 C). ESI-HRMS: m/z calcd
for C6 H4 BrFO + :
190.9430; found: 190.9508.
6 Hansen PE.
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Jackobsen HJ.
Manzara AP.
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