PAPER
Novel 3-Alkyl- and 3-Aryl-4-iodophenols
223
4-Iodo-3-isopropylphenol (1a) and 2-Iodo-5-isopropylphenol
(5a)
4-Iodobiphenyl-3-ol (5b)
Yield: 2.15 g (62%); Rf = 0.43 (hexane–CH2Cl2, 4:1).
To a stirred soln of commercially available 3-isopropylphenol (4a,
10.0 g, 73.4 mmol) in MeOH (250 mL) was added a soln of ICl
(11.9 g, 73.4 mmol) in MeOH (100 mL) over 1 h. After stirring at
r.t. for 16 h, the mixture was quenched with 20% aq Na2S2O3 (50
mL), stirred for 20 min, and concentrated to give a two-phase mix-
ture. H2O (200 mL) was added and the mixture was extracted with
EtOAc (2 × 150 mL). The combined organic phases were dried
(MgSO4), filtered, and concentrated to dryness. The crude product
was purified by column chromatography (silica gel, gradient hexane
to hexane–CH2Cl2, 1:1).
1H NMR (500 MHz, CDCl3): d = 7.70 (d, J = 8 Hz, 1 H, H3), 7.55–
7.58 (m, 2 H, Haryl), 7.42–7.45 (m, 2 H, Haryl), 7.35–7.38 (m, 1 H,
Haryl), 7.23 (d, J = 2 Hz, 1 H, H6), 6.93 (dd, J = 8, 2.5 Hz, 1 H, H4),
5.30 (s, 1 H, OH); NOE cross peaks observed: H4 and H6 to
d = 7.55–7.58.
13C NMR (125 MHz, CDCl3): d = 155.07, 143.75, 139.74, 138.38,
128.87, 127.87, 126.95, 121.34, 113.69, 84.33.
HPLC/MS: m/z = 295 (M–).
Anal. Calcd for C12H9IO: C, 48.68; H, 3.06. Found: C, 48.65; H,
2.99.
4-Iodo-3-isopropylphenol (1a)
Yield: 7.88 g (41%); Rf = 0.26 (hexane–CH2Cl2, 2:3).
3-tert-Butyl-4-iodophenol (1c); Typical Procedure
1H NMR (500 MHz, CDCl3): d = 7.63 (d, J = 8.5 Hz, 1 H, H5), 6.76
(d, J = 3.5 Hz, 1 H, H2), 6.43 (dd, J = 3, 8.5 Hz, 1 H, H6), 4.69 (s,
1 H, OH), 3.12 (sept, J = 7 Hz, 1 H, CH), 1.21 (d, J = 7 Hz, 6 H,
CH3); NOE cross peaks observed: H2 to d = 1.21.
13C NMR (125 MHz, CDCl3): d = 156.11, 151.96, 140.03, 115.24,
113.42, 89.51, 37.94, 22.95.
A soln of 5-tert-butyl-2,4-diiodophenol (6c, 2.63 g, 6.54 mmol) in
NMM (27 mL) was heated to reflux for 8 h. The mixture was con-
centrated under vacuum. The residues were taken up in EtOAc (50
mL) and washed with 2 M HCl (25 mL) and 20% Na2S2O3 soln (30
mL). The organic phase was dried (MgSO4), filtered, and concen-
trated under vacuum. The resulting oil was purified by column chro-
matography (hexane–CH2Cl2, 7:3 to 1:1); yield: 922 mg (51%);
Rf = 0.42 (hexane–CH2Cl2, 3:7).
HPLC/MS: m/z = 261 (M–).
Anal. Calcd for C9H11IO: C, 41.25; H, 4.23. Found: C, 41.35; H,
4.19.
1H NMR (500 MHz, CDCl3): d = 7.79 (d, J = 8 Hz, 1 H, H5), 6.94
(d, J = 3 Hz, 1 H, H2), 6.38 (dd, J = 2.9, 8.4 Hz, 1 H, H6), 4.65 (s,
1 H, OH), 1.50 (s, 9 H, CH3); NOE cross peaks observed: H2 to
d = 1.50.
13C NMR (125 MHz, CDCl3): d =155.33, 151.93, 144.17, 115.50,
114.69, 83.49, 36.56, 29.70.
2-Iodo-5-isopropylphenol (5a)
Yield: 5.34 g (28%); Rf = 0.54 (hexane–CH2Cl2, 2:3);
1H NMR (500 MHz, CDCl3): d = 7.54 (d, J = 8 Hz, 1 H, H3), 6.88
(d, J = 2 Hz, 1 H, H6), 6.57 (dd, J = 2.5, 8.5 Hz, 1 H, H4), 5.18 (s,
1 H, OH), 2.83 (sept, J = 7 Hz, 1 H, CH), 1.22 (d, J = 7 Hz, 6 H,
CH3); NOE cross peaks observed: H4 and H6 to d = 1.22.
13C NMR (125 MHz, CDCl3): d = 154.67, 151.95, 137.83, 120.99,
113.23, 81.92, 33.75, 23.75.
HPLC/MS: m/z = 261 (M–).
HPLC/MS: m/z = 275 (M–).
Anal. Calcd for C10H13IO: C, 43.50; H, 4.75. Found: C, 43.42; H,
4.68.
4-Bromo-3-tert-butylphenol (1d)
4-Bromo-5-tert-butyl-2-iodophenol (3,7 100 mg, 0.281 mmol) was
taken up in NMM (2 mL) and heated to reflux for 16 h. The soln was
cooled to r.t. and concentrated to dryness. The obtained oil was tak-
en up in EtOAc (50 mL) and washed with 2 M HCl (20 mL). The
organic phase was dried (MgSO4), filtered, and concentrated to dry-
ness. The resulting oil was purified by chromatography (silica gel,
hexane–CH2Cl2, 9:1 to 1:1); yield: 34 mg (50%); Rf = 0.20 (hexane–
CH2Cl2, 1:1).
HRMS: m/z calcd for C9H11IO: 261.9854; found: 261.9846.
Anal. Calcd for C9H11IO: C, 41.25; H, 4.23. Found: C, 41.71; H,
4.34.
6-Iodobiphenyl-3-ol (1b) and 4-Iodobiphenyl-3-ol (5b)
A soln of ICl (2.28 g, 14.1 mmol) in MeOH (10 mL) was added
dropwise to a stirred soln of commercially available biphenyl-3-ol
(4b, 2.00 g, 11.7 mmol) in MeOH (40 mL) over 1 h. The mixture
was stirred at r.t. for 20 h, quenched with 20% Na2S2O3 soln (30
mL) and stirred for a further 15 min. The mixture was concentrated
under vacuum to half of its volume and extracted with EtOAc
(2 × 100 mL). The combined organic phases were dried (Na2SO4),
filtered, and concentrated under vacuum to dryness. The resulting
oil was purified by chromatography (silica gel, hexane–CH2Cl2, 4:1
to 100% CH2Cl2).
1H NMR (500 MHz, CDCl3): d = 7.42 (d, J = 8.5 Hz, 1 H, H5), 6.93
(d, J = 2.5 Hz, 1 H, H2), 6.53 (dd, J = 8.5, 2.5 Hz, 1 H, H6), 4.68 (s,
1 H, OH), 1.48 (s, 9 H, CH3); NOE cross peaks observed: H2 to
d = 1.48.
2-Bromo-5-tert-butylphenol (2)
4-Bromo-5-tert-butyl-2-iodophenol (3,7 1.97 g, 5.56 mmol) was
taken up in 10% aq NaOH (80 mL). Zn powder (4.36 g, 66.7 mmol)
was added in 1 portion and the resulting suspension was heated to
100 °C for 2.5 h. The mixture was cooled to r.t. and filtered through
a pad of Celite. The filtrate was acidified to pH 1–2 with concd HCl
and extracted with EtOAc (2 × 100 mL). The combined organic lay-
ers were dried (MgSO4), filtered, and concentrated to dryness. The
resulting oil was purified by chromatography (silica gel, hexane–
Et2O, 95:5 to 4:1); yield: 1.27 g (quantitative); Rf = 0.51 (hexane–
Et2O, 4:1).
6-Iodobiphenyl-3-ol (1b)
Yield:0.41 g (12%); Rf = 0.20 (hexane–CH2Cl2, 4:1).
1H NMR (500 MHz, CDCl3): d = 7.76 (d, J = 8.5 Hz, 1 H, H5),
7.39–7.43 (m, 3 H, Haryl), 7.31–7.33 (m, 2 H, Haryl), 6.83 (d, J = 3
Hz, 1 H, H2), 6.59 (dd, J = 8.5, 3 Hz, 1 H, H6) 4.77 (s, 1 H, OH);
NOE cross peaks observed: H2 to d = 7.31–7.33.
13C NMR (125 MHz, CDCl3): d = 155.63, 147.79, 143.75, 140.27,
129.11, 127.97, 127.77, 117.47, 116.41, 87.19.
HPLC/MS: m/z = 295 (M–).
1H NMR (500 MHz, CDCl3): d = 7.35 (d, J = 8.5 Hz, 1 H, H3), 7.06
(d, J = 2.5 Hz, 1 H, H6), 6.84 (dd, J = 8.5, 2.5 Hz, 1 H, H4), 5.41 (s,
1 H, OH), 1.29 (s, 9 H, CH3); NOE cross peaks observed: H4 and
H6 to d = 1.29.
HRMS: m/z calcd for C12H9IO: 295.9698; found: 295.9706.
Anal. Calcd for C12H9IO: C, 48.68; H, 3.06. Found: C, 49.26; H,
3.06.
Synthesis 2008, No. 2, 221–224 © Thieme Stuttgart · New York