6890 J . Org. Chem., Vol. 63, No. 20, 1998
Zhang et al.
filtered and the precipitate was washed with CH2Cl2. The
filtrates were concentrated by rotary evaporation to give a
brown oil, and it was then redissolved in CH2Cl2 (30 mL),
washed with water and brine, and dried over MgSO4. Con-
centration using a rotary evaporator and subsequent chroma-
tography on silica gel using hexane/ethyl acetate (6:1) as the
eluent afforded 3,5-di-tert-butyl-2-(2′-pyridyl)anisole (6b) (127
mg, 86%) as colorless crystals; mp 105-107 °C (hexane/
CH2Cl2); Rf ) 0.25 (hexane/ethyl acetate ) 6:1); 1H NMR (250
MHz, CDCl3) δ 1.12 (s, 9 H), 1.36 (s, 9 H), 3.63 (s, 3 H), 6.85
(d, 1 H, J ) 1.5 Hz), 7.18-7.31 (m, 3 H), 7.65 (t, 1 H, J ) 7.6
Hz), 8.64 (dd, 1 H, J ) 1.7, 5.4 Hz), 13C NMR (125 MHz,
CDCl3): δ 31.4, 32.4, 35.1, 36.9, 56.0, 106.3, 116.5, 121.4, 127.0,
127.2, 134.9, 148.3, 148.5, 151.4, 157.5, 159.5; FABMS: m/z
for C20H27NO: C, 80.75; H, 9.16; N, 4.71. Found: C, 80.27;
H, 9.26; N, 4.60.
3,5-Di-ter t-bu tyl-2-(2′-p yr id yl)p h en ol (8b). A solution of
anisole 6b (250 mg, 0.84 mmol) in CH2Cl2 (8 mL) was added
32
to a solution of BBr3 (0.08 mL, 0.84 mmol) in CH2Cl2 (1 mL)
at -78 °C under N2. The reaction mixture was allowed to
warm to rt and stirred overnight. Then H2O (10 mL) was
added, the solution stirred for 10 min, and the organic layer
separated. The aqueous layer was neutralized with saturated
NaHCO3 to pH ) 6 and was then extracted with CHCl3 (10
mL × 3). The combined organic phase was washed with brine
and dried over MgSO4. After the solvent was removed, the
residue was purified by flash chromatography on silica gel with
a mixture of hexane/ethyl acetate (3:1) as the eluent to afford
3,5-di-tert-butyl-2-(2′-pyridyl)phenol (8b) as colorless crystals
(170 mg, 71%): mp 181-183 °C (CHCl3); Rf ) 0.23 (hexane/
(relative intensity) 297 (M+, 100). Anal. Calcd for C20H27
-
NO: C, 80.75; H, 9.16; N, 4.71. Found: C, 80.52; H, 9.26; N,
4.68.
1
ethyl acetate ) 3:1); H NMR (250 MHz, CDCl3) δ 1.15 (s, 9
3,5-Di-ter t-bu tyl-2-(2′-isoqu in olin yl)a n isole (6c). A si-
miliar procedure as that used in the preparation of 6a :
2-Chloroisoquinoline (5c) was used as the halopyridine, and
the reaction was refluxed for 10 h. After usual workup, 3,5-
di-tert-butyl-2-(2′-isoquinolinyl)anisole (6c) was obtained as
colorless crystals in 77% yield; mp 106-108 °C (hexane/
CH2Cl2); Rf ) 0.36 (hexane/ethyl acetate ) 6:1); 1H NMR (250
MHz, CDCl3) δ 1.01 (s, 9 H), 1.40 (s, 9 H), 3.48 (s, 3 H), 6.88
(s, 1 H), 7.30 (s, 1 H), 7.38 (t, 1 H, J ) 7.3 Hz), 7.58 (m, 3 H),
7.78 (d, 1 H, J ) 8.0 Hz), 8.60 (d, 1 H, J ) 5.8 Hz); 13C NMR
(62.9 MHz, CDCl3) δ 32.1, 32.9, 35.8, 37.6, 56.6, 107.0, 117.7,
120.2, 125.4, 127.1, 128.4, 130.1, 130.6, 136.2, 142.3, 150.0,
152.4, 158.5, 162.1; FABMS: m/z (relative intensity) (M+, 100).
H), 1.32 (s, 9 H), 5.72 (brs, 1 H), 6.85 (d, 1 H, J ) 1.8 Hz), 7.17
(d, 1 H, J ) 1.8 Hz), 7.30 (t, 1 H, J ) 6.1 Hz), 7.41 (d, 1 H, J
) 7.7 Hz), 7.73 (t, 1 H, J ) 7.7 Hz), 8.69 (d, 1 H, J ) 5.0 Hz);
13C NMR (62.9 MHz, CDCl3) δ 31.3, 32.8, 34.8, 36.9, 111.0,
116.9, 122.2, 124.3, 127.4, 136.2, 148.6, 149.4, 152.1, 153.6,
158.9; FABMS: m/z (relative intensity) 283 (M+, 100); IR
(neat): 3250 cm-1; HRMS (matrix, NBA) calcd for C19H25NO‚
H+ 284.2009, found 284.2001.
3,5-Di-ter t-bu tyl-2-(2′isoqu in olin yl)p h en ol (8c). A 10
mL round-bottom flask was charged with 3,5-di-tert-butyl-2-
(2′-isoquinolinyl)anisole (6c) (260 mg, 0.75 mmol) and NaI (330
mg, 2.25 mmol), CH3CN (2.0 mL) was added to the mixture,
the flask was flushed with N2, and Me3SiCl (0.29 mL, 2.25
mmol) was then added.33 The reaction mixture was refluxed
for 96 h under N2. H2O (5.0 mL) was added to the mixture,
and it was extracted with diethyl ether (5.0 mL × 3). The
extracts were washed with aqueous Na2S2O3 and brine and
dried over MgSO4. After the solvent was removed, the residue
was purified by flash chromatography with a solvent mixture
of hexane/ethyl acetate (3:1) as the eluent to afford 3,5-di-tert-
butyl-2-(2′-isoquinolinyl)phenol (8c) as colorless crystals (217
mg, 87%): mp 122-124 °C (CHCl3); Rf ) 0.29 (hexane/ethyl
acetate ) 3:1); 1H NMR (250 MHz, CDCl3) δ 1.00 (s, 9 H), 1.36
(s, 9 H), 6.87 (d, 1 H, J ) 1.8 Hz), 7.25 (d, 1 H, J ) 1.8 Hz),
7.49 (t, 1 H, J ) 6.6 Hz), 7.68 (m, 3 H), 7.86 (d, 1 H, J ) 8.0
Hz), 8.59 (d, 1 H, J ) 5.8 Hz); 13C NMR (62.9 MHz, CDCl3) δ
31.3, 32.3, 34.8, 37.0, 111.4, 117.0, 120.4, 122.3, 126.7, 127.3,
127.6, 129.8, 130.3, 136.0, 141.8, 149.3, 152.3, 153.5, 160.3;
FABMS: m/z (relative intensity) 333 (M+, 100); IR (neat): 3056
cm-1; Anal. Calcd for C23H27NO: C, 82.83; H, 8.17; N, 4.20.
Found: C, 82.49; H, 8.20; N, 4.20.
Anal. Calcd for
C24H29NO: C, 82.94; H, 8.42; N, 4.03.
Found: C, 82.83; H, 8.53; N, 3.91.
3,5-Di-ter t-bu tyl-2-(3′-m eth yl-2′-pyr idyl)ph en ol (8a). Py-
ridine (11.8 mL, 145 mmol) was added to 37% of hydrochloride
acid (12.1 mL, 145 mmol), and the mixture was stirred and
heated at 200 °C for 30 min. Then water was removed by
distillation at 220 °C to give a white solid of pyridinium
hydrochloride.31 3,5-Di-tert-butyl-2-(3′-methyl-2′-pyridyl)ani-
sole (6a ) (3.5 g, 11 mmol) was then added, and the mixture
was heated to 200 °C for 12 h under N2. After cooling to room
temperature, water (40 mL) was added. The reaction mixture
was neutralized with aqueous sodium hydroxide and was
extracted with CH2Cl2 (50 mL × 3). The extracts were washed
with brine and dried over MgSO4. After the solvent was
removed, the residue was purified by flash chromatography
with a solvent mixture of hexane/ethyl acetate (3:1) as the
eluent to afford 3,5-di-tbutyl-(3′-2′-methylpyridyl)phenol (8a )
as colorless crystals (2.7 g, 83%): mp 162-164 °C (CHCl3); Rf
) 0.21 (hexane/ethyl acetate ) 3:1); 1H NMR (250 MHz, CDCl3)
δ 1.11 (s, 9 H), 1.32 (s, 9 H), 2.14 (s, 3 H), 4.60 (brs, 1 H), 6.84
(s, 1 H), 7.16 (s, 1 H), 7.21-7.26 (m, 1 H), 7.59 (d, 1 H, J ) 7.5
Hz), 8.49 (d, 1 H, J ) 4.1 Hz); 13C NMR (62.9 MHz, CDCl3) δ
19.2, 31.3, 32.0, 34.8, 37.0, 110.9, 117.1, 122.8, 123.3, 134.8,
137.7, 146.9, 148.1, 152.0, 152.6, 157.8; FABMS: m/z (relative
Ack n ow led gm en t. We thank the Research Grants
Council of Hong Kong and the Direct Grant of the
Chinese University of Hong Kong for financial support.
J O980646Y
intensity) 297 (M+, 58); IR (neat): 3057 cm-1
. Anal. Calcd
(32) (a) Holligan, B. M.; J effery, J . C.; Norgett, M. K.; Schatz, E.;
Ward, M. D. J . Chem. Soc., Dalton Trans. 1992, 3345. (b) Dietrich-
Buchecker, C. O.; Sauvage, J . P. Tetrahedron 1990, 46, 503.
(33) Olah, G. A.; Narang, S. C.; Gupta, B. G. B.; Malhotra, R. J .
Org. Chem. 1979, 44, 1247.
(30) Cozort, J . R.; Outlaw, J . F., J r.; Hawkins, A.; Siegel, S. J . Org.
Chem. 1983, 48, 4190.
(31) McOmie, J . F. W.; Watts, M. L.; West, D. E. Tetrahedron 1968,
24, 2289.