A. Cordeiro, J. Shaw, J. O’Brien, F. Blanco, I. Rozas
FULL PAPER
6.6 Hz, 2 H), 3.84 (t, J = 6.6 Hz, 2 H), 7.51 (t, J = 7.6 Hz, 1 H),
7.56 (d, J = 8.4 Hz, 1 H), 7.67 (d, J = 7.6 Hz, 1 H) ppm.
2 H, CH2), 2.72 (t, J = 6.3 Hz, 2 H), 3.29 (q, J = 3.3 Hz, 2 H),
6.48 (d, J = 8.9 Hz, 1 H), 7.43 (br. s, 1 H, NH), 7.76 (d, J = 2.7 Hz,
1 H), 7.78 (dd, J = 2.7, J = 8.9 Hz, 1 H) ppm. 13C NMR (150 MHz,
DMSO): δ = 20.0 (CH2), 26.3 (CH2), 40.5 (CH2), 111.7 (arom),
119.1 (C=), 124.1 (arom), 125.2 (arom), 134.7 (C-NO2), 151.6 (C=)
N-Fluorenylmethyloxycarbonyl-1,2,3,4-tetrahydroquinoline (2f): To
a solution of THQ (3.75 mmol) in DCM (10 mL) at 0 °C, fluorenyl-
methyloxycarbonyl chloride (1.1 equiv.) and TEA (1.1 equiv.) were
added. After stirring overnight at room temperature, the solvent
was evaporated under reduced pressure. The residue was taken up
with EtOAc and washed with 1 n HCl (3ϫ15 mL) and brine
(2ϫ15 mL). The organic layer was dried (Na2SO4) and concen-
trated in vacuo to give 0.93 g (70%) of 2f as a yellow solid with m.p.
1
ppm. H NMR (600 MHz, CDCl3): δ = 1.97 (q, J = 6.0 Hz, 2 H,
CH2), 2.81 (t, J = 6.0 Hz, 2 H), 3.43 (q, J = 6.0 Hz, 2 H), 4.76 (br.
s, 1 H, NH), 6.38 (dd, J = 8.9, J = 3.7 Hz, 1 H), 7.90 (m, 2 H) ppm.
HRMS (ESI-, MeOH) m/z found [M – H]+ 177.0732, C9H10N2O2
requires [M – H]+ 177.0742. IR: ν = 3374 (NH), 1514 (NO ) cm–1.
˜
2
1
90–92 °C. H NMR (400 MHz, CDCl3): δ = 1.94 (q, J = 6.8 Hz, 2
Deprotection of N-Acetyl-8-nitro-1,2,3,4-tetrahydroquinoline (5c):
After dilution of 5c (0.5 g) with EtOH (5 mL), water (2.5 mL) and
HCl (1 mL) were added and the mixture was refluxed for 4 h. After
that, the mixture was diluted with water and 5a precipitated as a
red crystals (90%).
H), 2.79 (t, J = 6.8 Hz, 2 H), 3.75 (t, J = 6.8 Hz, 2 H), 4.31 (t, J =
6.4 Hz, 1 H, CH), 4.61 (d, J = 6.4 Hz, CH2), 7.03 (m, 2 H), 7.10
(m, 2 H), 7.32 (t, J = 7.6 Hz, 2 H.), 7.43 (t, J = 7.6 Hz, 2 H), 7.58
(d, J = 7.6 Hz, 2 H), 7.80 (d, J = 7.6 Hz, 2 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 23.4 (CH2), 27.2 (CH2), 44.8 (CH2), 47.3
(CH-Fmoc), 67.5 (CH2-Fmoc), 120.0, 123.7, 124.1, 124.9, 125.9,
127.1, 127.7, 128.5, 130.1, 137.9 (C=), 141.4 (C=), 143.9 (C=),
154.7 (CO) ppm. HRMS (ESI, MeOH) m/z found [M + H]+
8-Nitro-1,2,3,4-tetrahydroquinoline (5a): M.p. 48–50 °C (ref.[9]
71 °C). 1H NMR (600 MHz, DMSO): δ = 1.83 (q, J = 5.8 Hz, 2
H, CH2), 2.79 (t, J = 6.2 Hz, 2 H), 3.46 (br. q, 2 H), 6.51 (dd, J =
8.5, J = 6.8 Hz, 1 H), 7.21 (d, J = 6.8 Hz, 1 H), 7.85 (d, J = 8.5 Hz,
1 H), 8.46 (br. s, 1 H, NH) ppm. 13C NMR (150 MHz, DMSO): δ
= 19.8 (CH2), 27.6 (CH2), 41.4 (CH2), 114.3 (arom.), 124.2 (arom.),
125.6 (C-NO2), 130.1 (arom.), 135.3 (arom.), 143.3 (arom.) ppm.
1H NMR (600 MHz, CDCl3): δ = 2.00 (q, J = 6.0 Hz, 2 H, CH2),
2.86 (t, J = 6.0 Hz, 2 H), 3.55 (t, J = 6.0 Hz, 2 H), 6.51 (d, J =
7.0 Hz, 1 H), 7.14 (dd, J = 7.0, J = 1.7 Hz, 1 H), 7.99 (dd, J = 7.0,
J = 1.7 Hz, 1 H), 8.36 (br. s, 1 H, NH) ppm. 13C NMR (150 MHz,
CDCl3): δ = 20.1 (CH2), 27.8 (CH2), 41.3 (CH2), 114.3 (arom.),
124.7 (arom.), 128.8 (C-NO2), 130.9 (arom.), 134.9 (arom.), 143.4
(arom.) ppm. HRMS (ESI, MeOH) m/z found [M]+ 178.0746,
356.1575, C24H21NO2 requires [M + H]+ 356.1572. IR: ν = 1702
˜
(CO) cm–1.
N-Fluorenylmethyloxycarbonyl-6-nitro-1,2,3,4-tetrahydroquinoline
1f): To a solution of 2e (1 equiv.) in DCM (5 mL) at room tempera-
ture, concentrated sulfuric acid (1 equiv.) was added. Then, potas-
sium nitrate (1 equiv.) was added to the solution: the mixture was
stirred for 2:30 h and was quenched by pouring over ice. The solu-
tion was extracted with DCM, and the organic layer washed with
water and dried with Na2SO4. Finally, after concentration in vacuo,
1
Ͼ 99% of 1f was obtained as brown syrup. H NMR (400 MHz,
CDCl3): δ = 1.91 (q, J = 6.1 Hz, 2 H), 2.81 (t, J = 6.1 Hz, 2 H),
3.71 (t, J = 6.1 Hz, 2 H), 4.30 (t, J = 5.5 Hz, 1 H, CH), 4.74 (d, J
= 5.5 Hz, 2 H, CH2), 7.35 (t, J = 7.2 Hz, 2 H), 7.44 (t, J = 7.2 Hz,
2 H), 7.55 (br. d, 1 H), 7.58 (d, J = 7.3 Hz, 2 H), 7.80 (d, J =
7.3 Hz, 2 H), 7.84 (d, J = 7.7 Hz, 1 H), 7.94 (s, 1 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 22.3 (CH2), 27.5 (CH2), 45.1 (CH2),
47.1 (CH-Fmoc), 67.6 (CH2-Fmoc), 119.9 (Fmoc), 121.5 (arom),
123.4 (arom), 123.8 (arom), 124.5 (Fmoc), 127.0 (Fmoc), 127.7
(Fmoc), 130.0 (C=), 141.3 (C=), 143.4 (C=), 143.6 (C-NO2), 154.1
(CO) ppm. HRMS (ESI, MeOH) m/z found [M + Na]+ 423.1429,
C9H10N2O2 requires [M + H]+ 178.0742. IR: ν = 3375 (NH), 1511
˜
(NO2) cm–1.
Computational Details: Geometries of the stationary structures
were fully optimized at the B3LYP theoretical level with the 6-
31++G** basis set as implemented in the Gaussian 03 program.[18]
Frequency calculations have been carried out at the same computa-
tional level to confirm that all relevant structures correspond to
energetic minima or real transition states. For the condensed-phase
calculations, the PCM as implemented in Gaussian was employed
to account for continuum solvation effects.
C H N O requires [M + Na]+ 423.1423. IR: ν = 1707 (CO), 1511
˜
24 20
(NO2) cm–1.
2
4
Supporting Information (see footnote on the first page of this arti-
cle): Analytical and spectral characterization data of compounds
3a, 4a, 2c, 5c, 1d, 2d, 5d, 1e, 2e, 5e, 6e, 2f, 1f, 1a, and 5a. 1H NMR
spectrum of the aromatic region of the crude nitration reaction of
2e at 0 °C, isolated 6e and isolated 1e; and the molecular modelling
coordinates of the structures optimized.
Deprotection of N-Protected 6-Nitro-THQ (1c, 1d, 1e and 1f) and
N-Protected 8-Nitro-THQ (5c) Derivatives: Deprotection of N-Ace-
tyl-6-nitro-1,2,3,4-tetrahydroquinoline (1c) or 6-Nitro-N-pivaloyl-
1,2,3,4-tetrahydroquinoline (1d): After dilution of 1c (0.5 g) or 1d
(0.5 g) with ethanol (5 mL), water (2.5 mL) and HCl (1 mL) were
added, and the mixture refluxed for 4 h. Then, the mixture was
diluted with water and 1a precipitated as a red crystals in a 90%
yield.
Acknowledgments
Deprotection of 6-Nitro-N-trifluoroacetyl-1,2,3,4-tetrahydroquinol-
ine (1e): After dilution of 1e (0.6 g) in 25 mL of MeOH a solution
of K2CO3 (1.5 equiv.) in 20 mL of water was added. The mixture
was refluxed for 1 h, MeOH was then evaporated and the residue
washed three times with EtOH. The organic solution was dried
(Na2SO4) and concentrated under vacuum. Compound 1a was ob-
tained by crystallization as red crystals (85%).
This work has been funded by the Science Foundation Ireland,
Research Frontiers Program grant CHE275 (F. B.), the Fundación
Alfonso Martín Escudero (A. C.) and the School of Chemistry at
Trinity College Dublin (J. S.). All calculations were performed on
the IITAC cluster maintained by the Trinity Centre for High Per-
formance Computing and on the computer cluster maintained by
Prof. Alkorta’s laboratory at the Instituto de Quimica Medica
(CSIC, Madrid, Spain).
Deprotection of N-Fluorenylmethyloxycarbonyl-6-nitro-1,2,3,4-tetra-
hydroquinoline (1f): Compound 1f (0.1 g) was dissolved in 10 mL
of DCM. Then, 5 mL of pyrrolidine were added. After 5 min, the
reaction was finished yielding 1a as red crystals (85%).
[1] G. A. Olah, R. Malhotra, S. C. Narang, in: Nitration Methods
and Mechanisms; VCH Publishers, New York, 1989.
[2] L. Hoffman, W. Königs, Ber. Dtsch. Chem. Ges. 1883, 16, 727–
740.
6-Nitro-1,2,3,4-tetrahydroquinoline (1a): M.p. 160–162 °C (ref.[9]
161–162 °C). 1H NMR (600 MHz, DMSO): δ = 1.79 (q, J = 6.3 Hz,
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