4726
M. D. Bowman et al. / Tetrahedron 62 (2006) 4715–4727
4.4.3.4. 2,6-Di-(3-bromophenyl)-4-(4-hydroxy-3-meth-
0449959), CEM Corporation, and the UW-Madison for fi-
nancial support of this work and the W. M. Keck Foundation
for support of instrumentation at the UW Center for Chem-
ical Genomics. B.G.P. acknowledges support during the
2004–2005 academic year through a Wayland Noland
Undergraduate Chemistry Research Fellowship.
oxyphenyl)-pyridine (16l). THP-vanillin42 (500 mg, 2.1
mmol), 30-bromoacetophenone (836 mg, 4.2 mmol), and
NaOH (168 mg, 4.2 mmol) were ground together in a mortar
and pestle for 30 min. The resulting orange paste was al-
lowed to stand at room temperature for 1 h. The paste was
then transferred to a 70 mLTeflon MW reaction vessel along
with a magnetic stirring bar. A 0.5 mL aliquot of acetic acid
was added to the reaction vessel, followed by butanol
(5.0 mL) and hydroxylamine hydrogen chloride (510 mg,
7.3 mmol). The reaction vessel was closed tightly and heated
with stirring in theꢁ Milestone MW reactor fromꢁ room
temperature to 170 C over 10 min, held at 170 C for
10 min, and allowed to cool to room temperature over ca.
30 min. A 20 mL portion of water was added to the vessel,
and the reaction mixture was stirred for 8 h at room temper-
ature. Awhite solid gradually formed. This solid was filtered
to give 86 mg of triarylpyridine 16l (8% yield). TLC:
Rf¼0.55 (1% AcOH in CH2Cl2). 1H NMR: (300 MHz,
CDCl3) d 8.31 (t, J¼1.8 Hz, 2H), 8.11 (ddd, J¼7.8, 1.5,
1.2 Hz, 2H), 7.81, (s, 2H), 7.59 (ddd, J¼8.0, 2.2, 1.1 Hz,
2H), 7.40 (t, J¼8.0 Hz, 2H), 7.29 (dd, J¼8.3, 1.9 Hz, 1H),
7.20 (d, J¼1.9 Hz, 1H), 7.08 (d, J¼8.3 Hz, 1H), 5.81 (s,
1H), 4.04 (s, 3H); 13C NMR: (75 MHz, CDCl3) d 156.3,
150.8, 147.3, 147.2, 141.7, 132.3, 130.5, 130.3, 125.9,
123.2, 120.9, 117.6, 115.3, 109.6, 56.5; IR (ATR): 3509,
3061, 1601, 1567, 1548, 1518, 1478, 1469, 1442, 1422,
References and notes
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1387, 1369, 1350, 1271, 1241, 1212, 1177, 1120 cmꢄ1
;
ESI-MS: expected, 509.0; observed, m/z 509.9 [M+H+].
9. (a) Boyle, N. A.; Janda, K. D. Curr. Opin. Chem. Biol. 2002, 6,
339–346; (b) Tan, D. S.; Burbaum, J. J. Curr. Opin. Drug
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13. We use Whatman 1Chr chromatography paper for macroarray
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4.4.3.5. 2,6-Di-(3-methoxyphenyl)-4-(4-hydroxy-3-
methoxyphenyl)-pyridine (16r). Vanillin (1.00 g, 6.57
mmol), 30-methoxyacetophenone (1.97 g, 6.57 mmol),
NH4OAc (2.00 g, 25.9 mmol), and 30 mL of acetic acid
were combined in a 70 mL Teflon MW reaction vessel. A
magnetic stirring bar was added to the vessel. The vessel
was closed tightly and heated with stirring in the Milestone
ꢁ
MW reactor from room temperature to 180 C over
ꢁ
10 min, held at 180 C for 20 min, and allowed to cool to
room temperature over ca. 30 min. The MW heating se-
quence was repeated (1ꢀ). The reaction mixture was concen-
trated to an oil under reduced pressure. The oil was dissolved
in 50 mL of EtOAc and washed with satd aq NaHCO3 (2ꢀ),
brine, and H2O. The organic phase was concentrated under
reduced pressure to give a brown oil. The oil was purified
by flash silica gel column chromatography (1% AcOH in
CH2Cl2) to give 65 mg of triarylpyridine 16r as a colorless
1
oil (2% yield). TLC: Rf¼0.26 (1% AcOH in CH2Cl2); H
NMR: (300 MHz, CDCl3) d 7.81 (s, 2H), 7.79 (dd, J¼2.6,
1.4 Hz, 2H), 7.74 (dt, J¼8.0, 1.4 Hz, 2H), 7.42 (t, J¼
8.0 Hz, 2H), 7.29 (dd, J¼8.2, 2.0 Hz, 1H), 7.21 (d, J¼
2.0 Hz, 1H), 7.07 (d, J¼8.2 Hz, 1H), 7.00 (dd, J¼8.0,
2.6 Hz, 2H), 5.79 (s, 1H), 4.01 (s, 3H), 3.92 (s, 6H); 13C
NMR: (75 MHz, CDCl3) d 160.2, 157.4, 150.3, 147.2, 147.0,
141.4, 131.5, 129.9, 120.8, 119.8, 117.3, 115.2, 114.8, 113.0,
109.7, 56.4, 55.6; IR (ATR): 3727, 3600, 3052, 1599, 1583,
1547, 1515, 1492, 1401, 1288, 1169, 1125 cmꢄ1; ESI-MS:
expected, 413.2; observed, m/z 414.1 [M+H+].
Acknowledgments
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4455–4458.
21. Wang, S. S. J. Am. Chem. Soc 1973, 95, 1328–1333.
We thank the Donors of the ACS Petroleum Research Fund
(41332-G1), the National Science Foundation (CHE-