The Journal of Organic Chemistry
Note
BuOH (2.7 mL) to yield the title compound as an off-white solid
(0.4064 g, 44%).
(3-Nitropropyl)benzene (2d). The title compound was synthe-
sized according to general procedure A using 3-phenylpropylamine
(0.0270 g, 0.2 mmol) and 2 g of dry silica gel. After reaction, the
product was isolated using flash chromatography (5% EtOAc/
Hexanes, Rf: 0.26). The title compound was isolated as a pale-yellow
3-Aminoadamantol (1k). Synthesized according to the liter-
ature.37 Adamantanamine (1 g, 5.33 mmol) was added to a pot of
premixed H2SO4 (10.3 mL) and nitric acid (1 mL) at 0 °C and
yielded the title product as a white solid (0.6987 g, 78%).
3,7-Dimethyloctyl Acetate (5a). Synthesized according to
literature precedent.38 3,7-Dimethyloctanol (0.96 mL, 5.0 mmol)
and acetyl chloride (0.43 mL, 6.0 mmol) were mixed to yield the title
compound as a colorless oil (0.7712 g, 77%).
General Procedure A. To a clean round-bottom flask was added
the corresponding amine (0.3 mmol), followed by pentane (20 mL).
A 3 g amount of silica gel (stored in a 140 °C oven overnight) was
added to form a slurry (0.1 mmol of substrate per gram of silica). The
solvent was slowly evaporated under reduced pressure (no lower than
800 mbar to avoid silica bumping as it dries) to yield silica gel loaded
with starting material. A 1 g amount of this impregnated silica gel was
added to an omnifit column measuring 150 mm long with an I.D. of
10 mm (Part number# 006EZ-10-15-AF). The silica plug measured
around 3 cm long inside the column. This assembly was connected to
a Vapourtec E-series (easy-Medchem) reactor and cooled down to
−60 °C using the with Vapourtec Cooling Module (#50-1314) under
a constant flow of oxygen through the reaction vessel (10 psi). Once
the reactor was cooled, the in-line ozone generator (Oxidation
Technologies, VMUS-DG1) was turned on. This was operated at
maximum power with an approximate flow rate of 0.12 L/min of
oxygen. This corresponds to an approximate production of 1.75 g/h
or 0.6 mmol of O3 per min. Ozone exit tubing from the reaction led to
a solution of sodium metabisulfite in water to quench any remaining
excess.
1
oil (0.0283 g, 85%). H NMR: (400 MHz, CDCl3) δ 7.34−7.16 (m,
5H), 4.37 (t, J = 6.9 Hz, 2H), 2.73 (t, J = 7.4 Hz), 2.37−2.30 (m,
2H). 13C{1H} NMR (100 MHz, CDCl3) δ 139.5, 128.7, 128.4, 126.6,
74.7, 32.3, 28.8. Spectral data were consistent with literature reports.42
1-(2-Nitroethyl)-4-(trifluoromethyl)benzene (2e). The title
compound was synthesized according to general procedure A using 2-
(4-trifluoromethylphenyl)ethylamine (0.0378 g, 0.2 mmol) using 2 g
of dry silica gel. After reaction the product was isolated using flash
chromatography (10% EtOAc/Hexanes, Rf: 0.33). The title
compound was isolated as a pale-yellow oil (0.0325 g, 74%). 1H
NMR: (400 MHz, CDCl3) δ 7.60 (d, J = 7.9 Hz, 2H), 7.34 (d, J = 7.9
Hz, 2H), 4.64 (t, J = 7.2 Hz, 2H), 3.38 (t, J = 7.2 Hz, 2H). 13C{1H}
NMR (100 MHz, CDCl3) δ 139.7, 129.0, 125.9 (quart), 122.6, 75.6,
33.0. Spectral data were consistent with literature reports.43
1-(2-Nitroethyl)-4-chlorobenzene (2f). The title compound
was synthesized according to general procedure A using 2-(4-
chlorophenyl)ethylamine (0.0311 g, 0.2 mmol) and 2 g of dry silica
gel. After reaction, the product was isolated using flash chromatog-
raphy (5% EtOAc/Hex, Rf: 0.15). The title compound was isolated as
1
a colorless oil (0.0271 g, 73%). H NMR: (400 MHz, CDCl3) δ
7.32−7.28 (m, 2H), 7.16−7.13 (m, 2H), 4.60 (t, J = 7.13 Hz, 2H),
3.29 (t, J = 7.13 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3) δ 134.1,
133.4, 129.9, 129.2, 76.0, 32.7. Spectral data were consistent with
literature reports.44
6-Nitrohexanoic Acid tert-Butyl Ester (2g). The title
compound was synthesized according to general procedure A using
tert-butyl-6-aminohexanoate (0.0375 g, 0.2 mmol) and 2 g of dry silica
gel. After reaction, the product was isolated using flash chromatog-
raphy (10% EtOAc/Hexanes, Rf: 0.21). The title compound was
isolated as a white solid (0.0294 g, 70%). 1H NMR: (400 MHz,
CDCl3) δ 4.38 (t, J = 7.0 Hz, 2H), 2.23 (t, J = 7.3 Hz, 2H), 2.06−1.99
(m, 2H), 1.67−1.58 (m, 2H), 1.44 (s, 9H), 1.42−1.39 (m, 2H).
13C{1H} NMR (100 MHz, CDCl3) δ 172.6, 80.4, 75.4, 35.0, 28.1,
27.1, 25.7, 24.2. IR: 1722, 1554, 1264, 1151, 730. HRMS (ESI-TOF)
m/z: [M + Na]+ Calcd for C10H19NO4Na: 240.1212; Found:
240.1202.
After 15 min, the ozone generation was turned off while allowing
oxygen to continue to flow. After the remaining ozone is purged from
the silica gel (∼10 s; loss of blue color), the reactor is allowed to
warm to room temperature. The silica gel was collected in a fritted
funnel, and ∼15 mL of MeOH were added to extract product. The
silica gel was then rinsed with 2 × 10 mL of EtOAc. The solvent was
removed by rotary evaporation. The column was cleaned with acetone
before repeating the above procedure again. In isolations, two
combined 1 g reactions were directly dry loaded to a column of silica
gel for purification following a pentane wash to remove excess grease
without further extraction.
General Procedure B. Identical to General Procedure A, but
reactor is cooled to −20 °C and ozone is applied for 60 min.
1-Nitrododecane (2a). The title compound was synthesized
according to general procedure A using dodecylamine (0.0370 g, 0.2
mmol) and 2 g of dry silica gel. After reaction, the product was
isolated using flash chromatography (5% EtOAc/Hexanes, Rf: 0.43).
1,1-Diethoxy-4-nitrobutane (2h). The title compound was
synthesized according to general procedure A using 1,1-diethoxy-4-
aminobutane (0.0322 g, 0.2 mmol) and 2 g of dry silica gel. After
reaction, the product was isolated using flash chromatography (25%
EtOAc/Hexanes, Rf: 0.47). The title compound was isolated as a
yellow oil (0.0352g, 92%). 1H NMR: (400 MHz, CDCl3) δ 4.50 (t, J
= 5.3 Hz, 1H), 4.42 (t, J = 7.0 Hz, 2H), 3.68−3.60 (dq, J = 9.4, 7.1
Hz, 2H), 3.51−3.44 (dq, J = 9.4, 7.1 Hz, 2H), 2.13−2.06 (m, 2H),
1.73−1.68 (m, 2H), 1.20 (t, J = 7.1 Hz, 6H). 13C{1H} NMR (100
MHz, CDCl3) δ 102.0, 75.4, 61.7, 30.3, 22.6, 15.3. Spectral data were
consistent with literature reports.45
1
The title compound was isolated as a yellow oil (0.013 g, 62%). H
NMR: (400 MHz, CDCl3) δ 4.38 (t, J = 7.1 Hz, 2H), 2.00 (quin, J =
7.1 Hz, 2H), 1.42−1.20 (m, 18H), 0.88 (t, J = 6.8 Hz, 3H). 13C{1H}
NMR (100 MHz, CDCl3) δ 75.7, 31.9, 29.7, 29.6, 29.4, 29.3, 29.2,
28.8, 27.4, 26.2, 22.7, 14.1. Spectral data were consistent with
literature reports.39
tert-Butyl Nitrophenylpropanoate (2i). The title compound
was synthesized according to general procedure A using phenylalanine
tert-butyl ester (0.0443 g, 0.2 mmol) and 2 g of dry silica gel. After
reaction, the product was isolated used flash chromatography (5%
EtOAc/Hexanes, Rf: 0.35). The title compound was isolated as a
Nitrocyclohexane (2b). The title compound was synthesized
according to general procedure A using cyclohexylamine (0.0298 g,
0.3 mmol) and 3 g of dry silica gel. Crude NMR: 80%. After reaction,
the product was isolated using flash chromatography (10% EtAOc/
Hexanes, Rf: 0.44). The title compound was isolated as a yellow oil
1
white solid (0.0333 g, 66%). H NMR: (400 MHz, CDCl3) δ 7.33−
1
(0.0216 g, 56%). H NMR: (400 MHz, CDCl3) δ 4.36 (tt, J = 10.7,
7.20 (m, 5H), 5.25 (dd, J = 9.3, 5.9 Hz), 3.55−3.40 (m, 2H), 1.46 (s,
9H). 13C{1H} NMR (100 MHz, CDCl3) δ 162.9, 134.3, 128.9, 128.8,
127.7, 89.9, 84.8, 36.2, 27.7. IR: 2982, 1742, 1561, 1456, 1370, 1149.
HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C13H16NO4: 250.1079;
Found: 250.1075.
4.0 Hz, 1H), 2.26−2.19 (m, 2H), 1.91−1.82 (m, 4H), 1.69−1.62 (m,
1H), 1.39−1.23 (m, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 84.6,
30.9, 24.7, 24.1. Spectral data were consistent with literature reports.40
Nitroadamantane (2c). The title compound was synthesized
according to general procedure A using adamantylamine (0.0306 g,
0.2 mmol) and 2 g of dry silica gel. After reaction, the product was
isolated using flash chromatography (5% EtOAc/Hexanes, Rf: 0.44).
The title compound was isolated as a yellowish solid (0.0290 g, 80%).
1H NMR: (400 MHz, CDCl3) δ 2.23 (s, 3H), 2.21 (s, 6H), 1.77−1.66
(m, 6H). 13C{1H} NMR (100 MHz, CDCl3) δ 84.7, 40.8, 35.5, 29.7.
Spectral data were consistent with literature reports.41
Trans-4-Nitrocyclohexanol (2j). The title compound was
synthesized according to general procedure A using trans-4-
aminocyclohexanol (0.0230 g, 0.2 mmol) and 2 g of dry silica gel.
After reaction, the product was isolated using flash chromatography
(50% EtOAc/Hexanes, Rf: 0.31). The title compound was isolated as
white needle-like crystals (0.0167 g, 58% yield). 1H NMR: (400 MHz,
CDCl3) δ 4.39 (tt, J = 10.8, 4.1 Hz, 1H), 3.76 (tt, J = 9.9, 4.1 Hz, 1H),
E
J. Org. Chem. XXXX, XXX, XXX−XXX