Chemoselective Reduction of Aromatic Nitro Groups
J . Org. Chem., Vol. 66, No. 3, 2001 923
compounds and their spectroscopic data and melting points
matched those of commercially available material.
efficient, and economical condition that should prove
useful in functional group transformation in organic
synthesis.
ter t-Bu tyl-(2-n itr oben zyloxy)d ip h en ylsila n e 8. To a
solution of 2-nitrobenzyl alcohol (5.32 g, 33.6 mmol) in
anhydrous DMF (60 mL) were added imidazole (2.74 g, 40.3
mmol) and TBDPSCl (8.6 mL, 33.6 mmol). The reaction
mixture was stirred at room temperature for 2 h, quenched
with water (50 mL), and extracted with Et2O (3 × 60 mL).
The combined organic phase was washed with brine (50 mL),
dried over anhydrous MgSO4, filtered through a pad of cotton,
and concentrated in vacuo. The residue was purified by flash
column chromatography on silica gel with EtOAc and hexanes
as the eluent (hexanes:ethyl acetate ) 11:1 f 10:1 f 9:1) to
give 8 as a white solid (12.86 g, 98%). Rf ) 0.35 (hexanes:ethyl
Exp er im en ta l Section
Gen er a l Meth od s. All glassware used in our experiments
was evacuated, flame-dried, and flushed with argon before use.
Reactions were performed under argon, unless otherwise
noted. Solvents were either ACS reagent grade or HPLC grade
and were subjected to the following purification procedures
before use. Et2O and THF were freshly distilled from sodium/
benzophenone under argon. MeOH was redistilled from sodium
methoxide and stored over 4 Å molecular sieves. CH2Cl2 was
freshly distilled from calcium hydride. Triethylamine (Et3N)
was distilled from calcium hydride and stored over potassium
hydroxide. CDCl3 was stored over magnesium turning and
filtered through a short column packed with basic aluminum
oxide. N,N-Dimethylformamide (DMF) was stored over anhy-
drous 4 Å molecular sieves for at least one week before use.
Pyridine was dried over potassium hydroxide for 24 h at room
temperature followed by distillation over CaH2 under nitrogen
and then stored over 4 Å molecular sieves in the darkness.
p-Toluenesulfonyl chloride was recrystallized from hexanes
before use. 1,1′-Dioctyl-4,4′-bipyridinium dibromide was pur-
chased from TCI America (Portland, OR). Samarium(0) powder
and other commercially available compounds were purchased
from Aldrich Chemical Co. (Milwaukee, WI) and used without
further purification.
1
acetate ) 9:1); mp 75-77 °C; H NMR (CDCl3) δ 8.16-8.10
(m, 2H), 7.79-7.71 (m, 5H), 7.52-7.28 (m, 7H), 5.21 (s, 2H),
1.19 (s, 9H); 13C NMR (CDCl3) δ 138.0, 135.7, 134.1, 133.1,
130.1, 128.2, 128.0, 127.7, 124.8, 63.1, 27.1, 19.6; IR (KBr):
3056.4, 2964.1, 2923.1, 1517.9, 1333.3 cm-1; FABMS (in
3-nitrobenzyl alcohol matrix) m/z (relative intensity) 392 (6,
MH+), 334 (100), 314 (29), 197 (42).
2-(ter t-Bu t yld ip h en ylsila n yloxym et h yl)p h en yla m in e
9. Yield, 92%; Rf ) 0.3 (hexanes:ethyl acetate ) 3:1); 1H NMR
(CDCl3) δ 7.80-7.76 (m, 4H), 7.52-7.41 (m, 6H), 7.18 (t, J )
7.1 Hz, 1H), 6.96 (dd, J ) 7.3, 1.5 Hz, 1H), 6.79-6.70 (m, 2H),
4.80 (s, 2H), 4.30 (br s, 2H, N-H), 1.13 (s, 9H); 13C NMR
(CDCl3) δ 146.2, 135.8, 133.4, 130.0, 128.8, 128.7, 127.9, 125.0,
118.1, 115.8, 65.6, 27.0, 19.4; IR (neat): 3456.4, 3374.3 cm-1
;
FABMS (in 3-nitrobenzyl alcohol matrix) m/z (relative inten-
sity) 361 (32, M+), 304 (100); HRMS (FAB) (in 3-nitrobenzyl
alcohol matrix) m/z calcd for C23H27NOSi (M+) 361.1862, found
361.1862.
Unless otherwise stated, all reactions were magnetically
stirred and monitored by thin-layer chromatography (TLC)
using 0.25 mm Whatman precoated silica gel plates. TLC
plates were visualized using either 7% (w/w) ethanolic phos-
phomolybdic acid or 1% (w/w) aqueous potassium permagnate
containing 1% (w/w) NaHCO3. Flash column chromatography
was performed using silica gel (Merck 230-400 mesh). Yields
were based on the chromatographically and spectroscopically
pure compounds.
(2-Meth yl-5-n itr op h en yl)ca r ba m ic Acid ter t-Bu tyl Es-
ter 12. A solution of 5-nitro-o-toluidine (350 mg, 2.3 mmol) in
MeOH (20 mL) was charged with NaHCO3 (396 mg, 4.6 mmol)
and (t-Boc)2O (510 mg, 2.3 mmol). The reaction mixture was
sonicated for 4 h and evaporated in vacuo to remove most of
the solvent. The residue was diluted with EtOAc (200 mL) and
brine (60 mL). The organic phase was dried over anhydrous
Na2SO4, filtered through a pad of cotton, and concentrated in
vacuo. The residue was purified by flash column chromatog-
raphy on silica gel with EtOAc and hexanes as the eluent
(hexanes:EtOAc ) 7:1 f 6:1 f 5:1) to give 12 as a brownish
crystal (487 mg, 85%). Rf ) 0.45 (hexanes:EtOAc ) 3:1); mp
143-144 °C;1H NMR (CDCl3) δ 8.81 (d, J ) 2.6 Hz, 1H), 7.82
(dd, J ) 16.4, 2.6 Hz, 1H), 7.30-7.26 (m, 2H), 6.51 (br s, 1H),
2.35 (s, 3H), 1.55 (s, 9H); 13C NMR (CDCl3) δ 152.5, 147.2,
137.6, 133.7, 130.9, 118.0, 114.9, 81.8, 28.4, 18.2; IR (KBr):
3342.5, 1697.5 cm-1; FABMS (in 3-nitrobenzyl alcohol matrix)
m/z (relative intensity) 252 (47, M+), 197 (100), 180 (9).
(5-Am in o-2-m eth ylp h en yl)ca r ba m ic Acid ter t-Bu tyl
Ester 13. Yield, 79%; Rf ) 0.25 (hexanes:ethyl acetate ) 3:1);
1H NMR (CDCl3) δ 7.34 (d, J ) 1.6 Hz, 1H), 6.89 (d, J ) 8.2
Hz, 1H), 6.33 (dd, J ) 2.6, 8.0 Hz), 6.28 (br s, 1H), 3.58 (br s,
2H), 2.13 (s, 3H), 1.52 (s, 9H); 13C NMR (CDCl3) δ 153.0, 145.5,
137.2, 131.0 116.2, 110.3, 107.2, 80.5, 28.6, 17.0; IR (KBr):
3425.6, 3333.3, 3312.8, 1692.3 cm-1; FABMS (in 3-nitrobenzyl
alcohol matrix) m/z (relative intensity) 222 (80, M+), 166 (100);
HRMS (FAB) (in 3-nitrobenzyl alcohol matrix) m/z calcd for
Melting points were determined using a Mel-Temp ap-
paratus and are uncorrected. Infrared spectra were recorded
with a Perkin-Elmer model 1600 series FTIR spectrometer
using polystyrene as an external standard. Infrared absor-
1
bance is reported in reciprocal centimeters (cm-1). All H and
13C NMR spectra were recorded on a Varian Gemini 200 MHz
spectrometer at ambient temperature. Chemical shifts (200
MHz for 1H and 50 MHz for 13C) are reported in parts per
1
million (δ) relative to CDCl3 (δ 7.24 for H and 77.0 for 13C) or
DMSO-d6 (δ 2.49 for 1H and 39.5 for 13C). Coupling constants
(J values) are given in hertz (Hz). Mass spectral data were
obtained from the University of Kansas Mass Spectrometry
Laboratory (Lawrence, KS).
Gen er a l P r oced u r es for th e Red u ction of Nitr o Com -
p ou n d s. A flame-dried, 50 mL, round-bottomed, two-neck
flask equipped with a Teflon-coated magnetic stirring bar was
flushed with dried argon and charged with substrate (1 mmol)
in anhydrous MeOH (30 mL). To the well-stirred clear solution
were added sequentially a catalytic amount of 1,1′-dioctyl-4,4′-
bipyridinium dibromide (22 mg, 0.05 mmol) and Sm (301 mg,
2 mmol). The deep blue suspension formed was stirred
vigorously at room temperature until TLC showed disappear-
ance of the starting material. At the end of reaction, saturated
aqueous NH4Cl (50 mL) and Et2O (100 mL) were added to
partition the reaction mixture. The aqueous phase was sepa-
rated and extracted with Et2O (2 × 50 mL). The combined
ether phase was washed with brine (50 mL) and dried over
anhydrous MgSO4. After filtration and removal of organic
solvent under reduced pressure, the residue was purified by
flash column chromatography using ethyl acetate (EtOAc)/
hexanes (0.5% Et3N) to give the desired aromatic amine
product.35 Compounds 3, 5, 7, 11, 21, 23, and 25 are known
C
12H18N2O2 (M+) 222.1368, found 222.1368; N, N′-Bis-[3-(t-
Boc-a m in o)-4-m et h ylp h en yl]h yd r a zin e 30. Yield, 11%;
Rf ) 0.5 (hexanes:ethyl acetate ) 3:1); mp 114-116 °C; 1H
NMR (CDCl3) δ 8.30 (s, 1H), 7.73 (dd, J ) 15.8, 2.2 Hz, 1H),
7.41 (d, J ) 8.0 Hz, 1H), 7.29 (s, 1H), 6.45 (s, 1H), 2.35 (s,
3H), 1.55 (s, 9H); 13C NMR (CDCl3) δ 166.1, 152.7, 137.7, 135.1,
131.1, 118.1, 111.3, 81.5, 28.5, 18.5; IR (neat): 3333.3, 2974.3,
1692.3 cm-1; FABMS (in 3-nitrobenzyl alcohol matrix) m/z
(relative intensity) 442 (3, M+), 327 (21), 316 (50), 222 (2), 181
(100); HRMS (FAB) (in 3-nitrobenzyl alcohol matrix) m/z calcd
for C24H34N4O4 (M+) 442.2580, found 442.2608.
3-Vin ylp h en yla m in e 15.36 Yield, 82%; Rf ) 0.35 (hexanes:
1
ethyl acetate ) 4:1); H NMR (CDCl3) δ 7.13 (t, J ) 18 Hz,
1H), 6.83 (d, J ) 8 Hz, 1H), 6.73 (s, 1H), 6.70-6.55 (m, 2H),
5.70 (d, J ) 18 Hz, 1H), 5.20 (d, J ) 11 Hz, 1H), 3.85 (br s,
2H); 13C NMR (CDCl3) δ 146.4, 138.1, 136.7, 128.9, 116.2,
(35) Because aromatic amine products are known to be unstable
upon exposure to air and light, all products should be handled with
care and stored under argon at low temperature.