F. Thomas et al.
FULL PAPER
114.5 (d), 140.2 (s), 147.5 (s), 153.9 (s); MS (DCI, NH3 isobutane): m/z:
154 (2,4-dimethoxyphenol); elemental analysis calcd (%) for C8H10O3: C
62.33, H 6.54; found: C 62.34, H 7.04.
rified by column chromatography on silica gel, eluting first with metha-
nol/ethyl acetate (6:1) and then with methanol. HLotBu (740 mg, 60%)
was obtained as a white solid. 1H NMR (300 MHz, CDCl3, 298 K, TMS):
4
HLoOMe: 2,4-Dimethoxyphenol (462 mg, 3 mmol), bis(2-pyridylmethyl)-
amine (537 mg, 3 mmol), and formaldehyde (1.11 mL of a 37% aqueous
solution) in EtOH/H2O (4:6, 10 mL) were heated for 24 h at 808C. The
reaction mixture was then extracted with CH2Cl2 (2î50 mL) and the or-
ganic layer was dried (Na2SO4) and concentrated. The ligand was purified
by column chromatography on neutral alumina (+3% isopropylamine)
with CH2Cl2/ethyl acetate (1:1) as eluent. HLoOMe (439 mg, 40%) was
d = 1.28 (s, 9H), 3.79 (s, 2H), 3.87 (s, 4H), 3.90 (s, 3H), 6.66 (d, J(H,H)
= 2.3 Hz, 1H), 6.85 (d, 4J(H,H) = 2.3 Hz, 1H), 7.14 (m, 2H), 7.39 (d,
3J(H,H) = 9 Hz, 2H), 7.61 (m, 2H), 8.56 (d, 3J(H,H) = 6 Hz, 2H); 13C
NMR (75 MHz, CDCl3, 298 K, TMS): d = 53.9 (q), 55.1 (t), 57.2 (t), 97.6
(d), 103.7 (d), 120.3 (d), 120.9 (s), 121.3 (d), 135.0 (d), 138.9 (s), 147.0 (d),
150.3 (s), 156.3 (s); MS (DCI, NH3 isobutane): m/z: 365 (HLotBu); ele-
mental analysis calcd (%) for C24H29N3O2: C 73.63, H 7.47, N 10.73;
found: C 74.06, H 7.75, N 10.34.
1
obtained as a beige solid. H NMR (200 MHz, CDCl3, 298 K, TMS): d =
3.76 (s, 2H), 3.87 (s, 4H), 3.88 (s, 3H), 6.25 (d, 3J(H,H) = 2.7 Hz, 1H),
3
3
6.46 (d, J(H,H) = 2.7 Hz, 1H), 7.15 (m, 2H), 7.37 (d, J(H,H) = 12 Hz,
2H), 7.61 (m, 2H), 8.55 (d, 3J(H,H) = 3.9 Hz, 2H); 13C NMR (75 MHz,
CDCl3, 298 K, TMS): d = 53.9 (q), 55.1 (t), 57.2 (t), 97.6 (d), 103.7 (d),
120.3 (d), 120.9 (s), 121.3 (d), 135.0 (d), 138.9 (s), 147.0 (d), 150.3 (s),
156.3 (s); MS (DCI, NH3 isobutane): m/z: 365 (HLoOMe); elemental
analysis calcd (%) for C21H23N3O3: C 69.02, H 6.34, N 11.50; found: C
68.89, H 6.31, N 11.46.
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2-Bromo-4-tert-butylphenol: 4-tert-Butylphenol (5 g, 27.7 mmol) and
tetra-n-butylammonium tribromide (16 g, 27.7 mmol) were dissolved in
CH2Cl2/methanol (9:6; 150 mL) and the solution was stirred for 30 min at
room temperature. The solvents were then evaporated and the concen-
trated reaction mixture was added to water (50 mL) and extracted with
diethyl ether (2îî50 mL). The combined organic layers were washed
with NaCl, dried (Na2SO4), and concentrated. The solvent was evaporat-
ed and 2-bromo-4-tert-butylphenol (5.71 g, 90%) was obtained as a color-
1
less oil. H NMR (300 MHz, CDCl3, 298 K, TMS): d = 1.27 (s, 9H), 6.94
(d, 3J(H,H) = 6.4 Hz, 1H), 7.22 (dd, 4J(H,H) = 2.3 Hz, 1H), 7.43 (d,
3J(H,H) = 2.3 Hz, 1H); 13C NMR (75 MHz, CDCl3, 298 K, TMS): d =
31.6 (q), 34.6 (s), 110.3 (s), 115.9 (d), 126.6 (d), 129.2 (d), 145.5 (s), 150.3
(s); MS (DCI, NH3 isobutane): m/z: 228 (2-bromo-4-tert-butylphenol);
elemental analysis calcd (%) for C10H13BrO: C 52.42, H 5.72, Br 34.88;
found: C 51.30, H 5.77, Br 33.72.
4-tert-Butyl-2-methoxyphenol:
2-Bromo-4-tert-butylphenol
(5 g,
21.8 mmol), anhydrous CuCl2 (1.5 g, 11.2 mmol), and sodium methoxide
(12 g, 0.218 mol) were dissolved in DMF (150 mL). The mixture was
heated under reflux for 1.5 h, filtered, and the solvent was evaporated.
The solution was poured into water and HCl was added until neutraliza-
tion. The mixture was extracted with CH2Cl2 and the combined organic
layers were washed with NaCl, dried (Na2SO4), and concentrated.
Column chromatography on silica gel (CH2Cl2 as eluent) yielded 4-tert-
butyl-2-methoxyphenol (3.14 g, 80%) as an orange oil. 1H NMR
(200 MHz, CDCl3, 298 K, TMS): d = 1.30 (s, 9H), 3.89 (s, 3H), 6.80 6.94
(m, 3H); 13C NMR (75 MHz, CDCl3, 298 K, TMS): d = 31.9 (s), 34.8
(q), 56.3 (q), 114.2 (d), 118.3 (d), 120.6 (d), 143.6 (s), 143.8 (s), 147.3 (s);
MS (DCI, NH3 isobutane): m/z: 180 (4-tert-butyl-2-methoxyphenol); ele-
mental analysis calcd (%) for C11H16O2: C 73.30, H 8.95; found: C 72.58,
H 8.69.
5-tert-Butyl-2-hydroxy-3-methoxybenzaldehyde: 4-tert-Butyl-2-methoxy-
phenol (1 g, 5.55 mmol) and hexamethylenediamine (0.8 g, 6.9 mmol)
were dissolved in trifluoroacetic acid (10 mL). The mixture was heated
under reflux for 2.5 h, hydrolyzed with 4 m hydrochloric acid (10 mL) for
12 h at room temperature, and extracted with CH2Cl2. The combined or-
ganic layers were washed with 4 m hydrochloric acid and brine, dried
(Na2SO4), and concentrated. Column chromatography on silica gel (di-
ethyl ether/pentane (1:7) as eluent) yielded 5-tert-butyl-2-hydroxy-3-me-
thoxybenzaldehyde (0.93 g, 80%) as a yellow solid. 1H NMR (300 MHz,
CDCl3, 298 K, TMS): d = 1.33 (s, 9H; tBu), 3.93 (s; OMe), 7.16 (dd,
4J(H,H) = 2.0 Hz, 2H), 9.90 (s, 1H; CHO); 13C NMR (75 MHz, CDCl3,
298 K, TMS): d = 31.9 (q), 34.8 (s), 56.8 (q), 116.9 (d), 120.5 (s), 121.0
(d), 143.2 (s), 148.2 (s), 150 (s), 197.2 (s); MS (DCI, NH3 isobutane): m/z:
208 (5-tert-butyl-2-hydroxy-3-methoxybenzaldehyde); elemental analysis
calcd (%) for C12H16O3: C 69.21, H 7.74; found: C 69.29, H 7.79.
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Pierre, Angew. Chem. 2002, 114, 3173; Angew. Chem. Int. Ed. 2002,
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L. Pierre, Chem. Eur. J. 2003, 9, 3803.
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Soc. Chim. Fr. 1997, 134, 785.
HLotBu:
5-tert-Butyl-2-hydroxy-3-methoxybenzaldehyde
(656 mg,
[9] F. Thomas, O. Jarjayes, H. Jamet, S. Hamman, E. Saint-Aman, C.
Duboc, J.-L. Pierre, Angew. Chem. 2004, 116, 604; Angew. Chem.
Int. Ed. 2004, 43, 594; b) T. Maki, Y. Araki, Y. Ishida, O. Onomura,
Y. Matsumura, J. Am. Chem. Soc. 2001, 123, 3371; c) L. Benisvy,
A. J. Blake, D. Collison, E. S. Davies, C. D. Garner, E. J. L. McInnes,
J. McMaster, G. G. Whittaker, C. Wilson, Chem. Commun. 2001,
3.15 mmol), bis(2-pyridylmethyl)amine (627 mg, 3.15 mmol), ten drops of
acetic acid, and sodium cyanoborohydride (198 mg, 3.15 mmol) in MeOH
(50 mL) were stirred for three days at room temperature. The reaction
mixture was extracted with CH2Cl2 and the combined extracts were
washed with brine, dried (Na2SO4), and concentrated. The ligand was pu-
4124
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Chem. Eur. J. 2004, 10, 4115 4125