N. BACKSTROM, N. A. BURTON AND C. I. F. WATT
1-(2-Methoxyphenyl)-2-nitropropane, 7(X ¼ H, L ¼ H): Sodium
hydroxide pellets (1.02 g) and sodium borohydride (1.02 g) were
dissolved in absolute ethanol (30 ml). In a separate flask,
1-(2-methoxyphenyl)-2-nitropropene (0.84 g) was dissolved in
absolute ethanol (20 ml) in a stirred cooled flask. Aliquots (ca
100 ml) of the sodium borohydride solution were then added, and
the reaction was monitored a few minutes after each addition by
loss of the broad absorption at 348 nm in the UV–Vis spectrum of
the mixture (5 ml of the mixture diluted in 5 mls of ethanol).
Reaction was complete after addition of 1.8 ml of borohydride
solution and 1 h at 0 8C. Any excess sodium borohydride was
destroyed by addition of acetone (2 ml). After stirring for 10 min,
solid carbon dioxide was added, followed by a few drops of
aqueous HCl to adjust the solution to pH 6 as judged by spotting
on wide-range pH paper. Saturated aqueous NaCl solution (40 ml)
was then added and the mixture was left undisturbed for 1 h
before extraction with ether. The combined ether layers were
dried over anhydrous Na2SO4, evaporated, and the resulting
yellow oil was subjected to bulb-to-bulb distillation (145–150 8C
at 1 mm Hg) to yield 1-(2-Methoxyphenyl)-2-nitropropane, as a
light yellow oil (0.61 g, 72%) which was a single component by
GLC and HPLC analysis. dH (500 MHz, CDCl3) 7.29 (1H, t, J ¼ 8.0),
7.11 (1H, d, J ¼ 7.8), 6.91 (2H, m), 4.95(1H, 6 lines, W ¼ 34.1),
3.87(3H, s), 3.30(1H, dd, J ¼ 13.6 and 7.4), 3.09(1H, dd, J ¼ 13.6 and
6.7 Hz); 1.56(3H, d, J ¼ 6.6); dC (75 MHz, CDCl3) 157.9, 131.4, 129.3,
124.4, 121.0, 110.7, 83.4, 55.5, 37.4, 19.8; nmax/cmꢁ1, 3064, 2936,
1539, 1439, 1238, 1124, 1021, 747; m/z (EI) 195(28%, Mþ., found
195.0898, calcd. for C10H13O3N, 195.0980), 151(69%), 148(100%),
120(82%), 115(57%), 91(100%), 84(44%), 77(39%), 49(81%).
2-Deuterio-1-(2-Methoxyphenyl)-2-nitropropane, 7(X ¼ H, L ¼ D):
1-(2-Methoxyphenyl)-2-nitropropane, 7(X ¼ H, L ¼ H), (1.02 g) was
dissolved in methanol-OD (5 ml) and pyridine (1 ml) added. The
reaction mixture was refluxed under nitrogen atmosphere for
purification was by column chromatography (silica, eluting with
ether: petrol 50:50 (v/v), containing 0.05% of formic acid) to yield
a near colourless oil (0.61 g, 89%).
For 3 (X ¼ H, L ¼ H), dH (500 MHz, CDCl3) 7.16 (1H, t, J ¼ 7.4),
7.09 (1H, d, J ¼ 7.4), 6.89 (1H, t, J ¼ 7.4), 6,76 (1H, d, J ¼ 7.4), 5.2(1H,
bs), 5.03(1H, 6 lines, W ¼ 34.2), 3.31(1H, dd, J ¼ 13.8 and 7.8);
3.11(1H, dd, J ¼ 13.8 and 6.3), 1.59(3H, d, J ¼ 6.6); dC (75 MHz,
CDCl3) 154.2, 131.9, 129.2, 122.6, 121.4, 115.8, 83.4, 36.7, 19.7;
nmax/cmꢁ1 3468, 2932, 1595, 1447, 1504; m/z(CI,NH3) 180(M-1),
146, 164, 131; (EI) 181, 134, 107; (ES ꢁve) 180 (100%, M-H, found
180.0661, calcd. for C9H10O3N, 180.0661)
For 3 (X ¼ H, L ¼ D), dH (500 MHz, CDCl3) 7.16 (1H, t, J ¼ 7.4),
7.09 (1H, d, J ¼ 7.4), 6.89 (1H, t, J ¼ 7.4), 6,76 (1H, d, J ¼ 7.4), 5.8(1H,
bs), 3.31(1H, d, J ¼ 13.8); 3.11(1H, d, J ¼ 13.8), 1.59(3H, s).
Integration of the H-NMR spectrum over the signal region
(d5.03) for the exchangeable site indicated deuterium incorp-
oration in excess of 97%.
1-(2-methoxy-5-nitrophenyl)-2-nitropropane, 7 (X ¼ NO2, L ¼ H
or D): 1-(2-Methoxyphenyl)-2-nitropropane (L ¼ H or D) (0.41 g,
2.1 mmol) was dissolved in glacial acetic acid (2 ml) and the
stirred solution cooled to 5 8C. A mixture of concentrated (70%)
nitric acid and acetic acid (2 ml dissolved in) was then added over
a period of 10 min, and the reaction was followed by tlc, which
indicated the formation of two new compounds. The solution
was allowed to warm to 20 8C and stirred for 4 h when it was
poured into ice-water (20 ml) and extracted with three portions
(5 ml each) of dichloromethane. The combined extracts were
dried over anhydrous magnesium sulfate and evaporated to yield
an oil containing residual acetic acid, which was pumped off
under high vacuum at 35 8C. Analysis of the resulting brown oil by
HPLC indicated the presence of two major components in ca 6:4
ratio and the major component was isolated by chromatography
on silica, eluting with 30:70 v/v ether: petrol containing 0.05% of
formic acid, to yield a light yellow oil (0.18 g, 0.79 mmol, 38%).
For 7 (X ¼ NO2, L ¼ H), dH (300 MHz, CDCl3) 8.10 (1H, dd, J ¼ 9.3
and 2.9), 7.92 (1H, d, J ¼ 2.9), 6.88 (1H, d, J ¼ 9.3), 4.85 (1H, 6 lines,
W ¼ 34.1), 3.89(3H, s), 3.22(1H, dd, J ¼ 13.8 and 8.5), 3.05(1H, dd,
J ¼ 13.8 and 5.8), 1.51(3H, d, J ¼ 6.6); dC (75 MHz, CDCl3) 162.5,
1
35 h, and the exchange was followed by H-NMR spectroscopy.
The solvent and pyridine were then removed under reduced
pressure and the residue was taken up in fresh methanol-OD
(2 ml) and pyridine (0.2 ml) added. The mixture was refluxed for
further 48 h before the solvent and pyridine were removed under
reduced pressure to leave a light yellow oil, purified by distillation
under vacuum. dH (300 MHz, CDCl3) 7.80 (1H, t, J ¼ 8.0), 7.11 (1H,
d, J ¼ 7.8), 6.91 (2H, m), 3.87(3H, s), 3.30(1H, d, J ¼ 13.6); 3.09(1H, d,
J ¼ 13.6); 1.57(3H, s); dC (75 MHz, CDCl3) 157.7, 131.2, 130.1, 124.2,
120.9, 110.6, 83.2, 55.5, 36.8, 19.2; nmax/cmꢁ1, 3064, 2939, 1602,
1575, 1495; m/z (EI) 196(26%, Mþ.), 152(63%), 149(100%),
121(80%), 115(57%), 91(100%). Integration of the H-NMR
spectrum over the signal region for the exchangeable site
(d4.95) indicated deuterium incorporation in excess of 97%.
1-(2-Hydroxyphenyl)-2-nitropropane, 3 (X ¼ H, L ¼ H and D):
1-(2-Methoxyphenyl)-2-nitropropane(X¼ H or D) (0.81 g, 4.1 mmol)
was dissolved in chloroform (5.0 ml), in a round bottom flask fitted
for inert atmosphere. The solution was cooled to ꢁ78 8C and stirred
under nitrogen. Boron tribromide (0.5 ml) was then added to the
solution by syringe, and the temperature of the reaction mixture
was allowed to rise to 20 8C and then to left undisturbed for 1 h.
The temperature was then reduced again to ꢁ80 8C and the
reaction was quenched by pouring the reaction mixture into cold
methanol (10.0 ml). The temperature was then allowed to rise to
room temperature, and the solvent was removed by evaporation
under reduced pressure. The residue was taken up in fresh
methanol (10 ml) and the solvent was removed again under
reduced pressure. This process was repeated, and tlc analysis
then indicated the presence of a single major product. Final
141.2, 126.5, 125.4, 125.2, 110.3, 82.2, 56.4, 36.1, 19.3; nmax/cmꢁ1
,
2942, 1546, 1512, 1336, 1260, 1100, and 1029; m/z(CI,NH3)
258(100%, M þ NH4), 193(71%); (EI) 240(8%, Mþ, found 240.0739,
calcd. for C10H12O5N2, 240.0741), 193 (100%) 166 (44%),
115(19%), 77(31%).
For 7 (X ¼ NO2, L ¼ D), dH (300 MHz, CDCl3) 8.10 (1H, dd, J ¼ 9.3
and 2.9), 7.92 (1H, d, J ¼ 2.9), 6.88 (1H, d, J ¼ 9.3), 3.89(3H, s),
3.21(1H, d, J ¼ 13.8), 3.04(1H, d, J ¼ 13.8), 1.50(3H, s). Integration
over of the H-NMR spectrum over the signal region (d4.85) for the
exchangeable site indicated deuterium incorporation in excess of
97%.
1-(2-Hydroxy-5-nitrophenyl)-2-nitropropane, 3 (X ¼ NO2, L ¼ H
and D): The methyl ethers were dissolved in chloroform (ca
30 mgs in 0.5 ml of chloroform) in a small RB flask with a well
fitting stopper. At room temperature, the reagent (BF3: SMe2,
0.5 ml) was added by a syringe in a single portion and the flask
stoppered and swirled to mix. The stoppered flask was then was
left undisturbed at 20 8C for 24 h with occasional swirling. A deep
red oil was deposited, which could be redissolved with a little
heating. After warming to ensure homogeneity, the liquid was
transferred by pipette to about 50 ml of methanol in an
ice-cooled RB flask. The flask was then placed on the rotavap
and the volume was reduced to about 3 ml of red liquid. This was
taken up in chloroform (20 ml) and partitioned with water. The
Copyright ß 2009 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2010, 23 711–722