Synthesis of 1- and 3-Nitrobenzo[a]pyrene
FULL PAPER
vided the by-product 9 (30 mg, 0.07 mmol, 2%). Overall, 760 mg
379 (5), 341 (4), 324 (5), 311 (23), 295 (12), 278 (5), 250 (27), 238
(1.8 mmol, 56%) of 6a and 230 mg (0.54 mmol, 17%) of 6b were (6), 125 (5).
isolated.
n-Hexyl 1-Nitrobenzo[a]pyrene-6-carboxylate (6a): Rf ϭ 0.21 (silica,
toluene/petroleum ether, 1:10). IR (KBr): ν˜ ϭ 2957 cmϪ1 (w), 2927
(w), 2856 (w), 1717 (vs), 1505 (m), 1333 (s), 843 (m), 824 (m), 750
(s), 695 (m). 1H NMR (400 MHz, CDCl3): δ ϭ 0.93 (t, J ϭ 7.1 Hz,
3 H, 6Ј-H), 1.35Ϫ1.41 (m, 4 H, 5Ј-H, 4Ј-H), 1.50Ϫ1.58 (m, 2 H,
3Ј-H), 1.91Ϫ1.98 (m, 2 H, 2Ј-H), 4.71 (t, J ϭ 6.5 Hz, 2 H, 1Ј-H),
7.83Ϫ8.00 (m, 2 H, 8-H, 9-H), 7.99 (d, J ϭ 9.3 Hz, 1 H, 4-H), 8.11
(d, J ϭ 8.3 Hz, 1 H, 3-H), 8.18 (d, J ϭ 9.3 Hz, 1 H, 5-H), 8.29
(‘‘d’’, J ϭ 8.3 Hz, 1 H, 7-H), 8.69 (d, J ϭ 8.3 Hz, 1 H, 2-H), 9.10
(‘‘d’’, J ϭ 9.0 Hz, 1 H, 10-H), 9.12 (d, J ϭ 9.7 Hz, 1 H, 12-H), 9.26
(d, J ϭ 9.7 Hz, 1 H, 11-H) ppm. 13C NMR (100 MHz, CDCl3):
δ ϭ 14.0 (q, C-6Ј), 22.6 (t, C-5Ј), 25.8 (t, C-3Ј), 28.8 (t, C-2Ј), 31.5
(t, C-4Ј), 66.5 (t, C-1Ј), 121.8 (s, C-12c), 123.1 (d, C-12), 123.4 (d,
C-10), 123.7 (d, C-2), 124.3 (s, C-12a), 124.3 (d, C-3), 125.4 (s, C-
5a), 125.4 (d, C-11), 125.8 (s, C-12b), 126.1 (d, C-7), 127.5 (d, C-
9), 127.8 (s, C-10b), 127.8 (d, C-8), 127.9 (s, C-6a), 128.1 (d, C-5),
128.2 (s, C-10a), 128.3 (d, C-4), 130.1 (s, C-6), 135.3 (s, C-3a), 143.6
(s, C-1), 169.5 (s, COO) ppm. MS: (EI): m/z (%) ϭ 425 (100) [Mϩ],
379 (5), 341 (4), 324 (5), 311 (23), 295 (12), 278 (5), 250 (27), 238
(6), 125 (5).
1-Nitrobenzo[a]pyrene-6-carboxylic Acid (7a): The ester 6a (100 mg,
0.24 mmol) was coated onto silica (by evaporation of a CH2Cl2
solution with 5 g of silica) and then heated at 280 °C for 4 h at a
pressure of less than 1·10Ϫ2 mbar. After cooling to room tempera-
ture, the silica was extracted with ethyl acetate (200 mL). From this
fraction, 6a (32 mg) was recovered. The silica was then transferred
to a Soxhlet extractor and was extracted with methanol for 10 h.
Evaporation of the methanol gave the acid 7a (61 mg, 0.18 mmol,
74%; 90% based on recovered starting material). TLC (silica, ethyl
acetate): Rf ϭ 0.00. IR (KBr): ν˜ ϭ 3430 cmϪ1 (vs), 3430 (w), 2927
(w), 2856 (w), 1581 (vs), 1518 (s), 1495 (m), 1305 (s), 840 (m), 745
1
(m). H NMR (400 MHz, [D4]MeOH): δ ϭ 7.90Ϫ7.94 ppm (m, 1
H, 8-H), 7.96Ϫ8.00 (m, 1 H, 9-H), 8.10 (d, J ϭ 9.3 Hz, 1 H, 4-H),
8.22 (d, J ϭ 8.3 Hz, 1 H, 3-H), 8.51 (d, J ϭ 9.3 Hz, 1 H, 5-H), 8.61
(‘‘d’’, J ϭ 8.0 Hz, 1 H, 7-H), 8.73 (d, J ϭ 8.3 Hz, 1 H, 2-H), 9.10
(d, J ϭ 9.5 Hz, 1 H, 12-H), 9.25 (‘‘d’’, J ϭ 8.5 Hz, 1 H, 10-H), 9.47
(d, J ϭ 9.5 Hz, 1 H, 11-H) ppm.
n-Hexyl 3-Nitrobenzo[a]pyrene-6-carboxylate (6b): Rf ϭ 0.21 (silica,
toluene/petroleum ether, 1:10). IR (KBr): ν˜ ϭ 2955 cmϪ1 (m), 2928
(w), 2860 (w), 1720 (vs), 1519 (m), 1326 (vs), 844 (m), 748 (m), 693
1
(w). H NMR (400 MHz, CDCl3): δ ϭ 0.92 (t, J ϭ 7.1 Hz, 3 H,
6Ј-H), 1.34Ϫ1.42 (m, 4 H, 5Ј-H, 4Ј-H), 1.52Ϫ1.56 (m, 2 H, 3Ј-H),
1.91Ϫ1.98 (m, 2 H, 2Ј-H), 4.72 (t, J ϭ 6.8 Hz, 2 H, 1Ј-H),
7.86Ϫ7.94 (m, 2 H, 8-H, 9-H), 8.20 (d, J ϭ 8.5 Hz, 1 H, 1-H), 8.26
(d, J ϭ 9.7 Hz, 1 H, 5-H), 8.30 (‘‘d’’, J ϭ 8.0 Hz, 1 H, 7-H), 8.34
(d, J ϭ 9.0 Hz, 1 H, 12-H), 8.55 (d, J ϭ 8.5 Hz, 1 H, 2-H), 8.77
(d, J ϭ 9.5 Hz, 1 H, 4-H), 9.05 (‘‘d’’, J ϭ 8.0 Hz, 1 H, 10-H), 9.15
(d, J ϭ 9.0 Hz, 1 H, 11-H) ppm. 13C NMR (100 MHz, CDCl3):
δ ϭ 14.0 (q, C-6Ј), 22.6 (t, C-5Ј), 25.8 (t, C-3Ј), 28.8 (t, C-2Ј), 31.5
(t, C-4Ј), 66.6 (t, C-1Ј), 122.3 (s, C-12c), 122.4 (d, C-2), 123.1 (d,
C-4), 123.4 (d, C-10), 124.9 (d, C-11), 125.0 (s, C-5a), 125.1 (s, C-
3a), 125.2 (s, C-12b), 126.0 (d, C-1), 126.3 (d, C-7), 27.5 (d, C-9),
127.8 (d, C-8), 127.9 (s, C-6a), 128.2 (d, C-12), 128.7 (s, C-10a),
128.8 (s, C-10b), 129.1 (d, C-5), 129.8 (s, C-6), 134.1 (s, C-12a),
150.7 (s, C-3), 169.4 (s, COO) ppm. MS: (EI): m/z (%) ϭ 425 (100)
[Mϩ], 379 (5), 341 (4), 324 (5), 311 (23), 295 (12), 278 (5), 250 (27),
238 (6), 125 (5).
No 13C NMR of 7a was recorded, due to its extremely low solu-
bility; an EI mass spectrum also failed.
3-Nitrobenzo[a]pyrene-6-carboxylic Acid (7b): By starting from the
ester 6b (100 mg, 0.24 mmol) and using the same procedure as de-
scribed for 7a, starting material (40 mg) and 7b (30 mg, 31%; 51%
based on recovered starting material) were obtained. Rf ϭ 0.00
(silica, ethyl acetate). IR (KBr): ν˜ ϭ 3453 cmϪ1 (vs), 2927 (w), 2925
(w), 2861 (w), 1562 (vs), 1519 (s), 1493 (m), 1317 (vs), 836 (m),
1
791 (w), 746 (m), 698 (w). H NMR (400 MHz, [D4]MeOH): δ ϭ
7.04Ϫ7.08 ppm (m, 1 H, 8-H), 7.10Ϫ7.14 (m, 1 H, 9-H), 7.52 (d,
J ϭ 9.0 Hz, 1 H), 7.62 (d, J ϭ 9.0 Hz, 1 H), 7.73 (d, J ϭ 9.5 Hz,
1 H), 7.75 (d, J ϭ 9.0 Hz, 1 H, 12-H), 7.78 (‘‘d’’, J ϭ 8.0 Hz, 1 H,
7-H), 7.83 (d, J ϭ 9.5 Hz, 1 H, 2-H), 8.39 (‘‘d’’, J ϭ 8.5 Hz, 1 H,
10-H), 8.55 (d, J ϭ 9.0 Hz, 1 H, 11-H) ppm. No 13C NMR of 7b
was recorded, due to its extremely low solubility; an EI mass spec-
trum also failed.
n-Hexyl 6-Nitrobenzo[a]pyrene-1-carboxylate (9): Rf ϭ 0.50 (silica,
toluene/petroleum ether, 1:10). IR (KBr): ν˜ ϭ 2963 cmϪ1 (m), 2933 1-Nitrobenzo[a]pyrene (8a): The crude acid 7a, resulting from silica
(w), 2860 (w), 1714 (vs), 1520 (s), 1356 (vs), 825 (m), 804 (m), 758
gel-supported ester pyrolysis, was suspended in freshly distilled
(m), 693 (w). 1H NMR (400 MHz, CDCl3): δ ϭ 0.95 (t, J ϭ 7.2 Hz, quinoline (80 mL). Copper powder (100 mg, 2.7 mmol) was added
3 H, 6Ј-H), 1.38Ϫ1.42 (m, 4 H, 5Ј-H, 4Ј-H), 1.42Ϫ1.61 (m, 2 H, and the degassed suspension was heated at reflux under argon for
3Ј-H), 1.89Ϫ1.96 (m, 2 H, 2Ј-H), 4.53 (t, J ϭ 6.6 Hz, 2 H, 1Ј-H),
7.88Ϫ7.93 (m, 2 H, 8-H, 9-H), 7.94 (d, J ϭ 9.5 Hz, 1 H, 4-H), 8.05 The solution was washed four times with half-concentrated hydro-
(d, J ϭ 9.5 Hz, 1 H, 5-H), 8.13 (d, J ϭ 7.8 Hz, 1 H, 3-H), 8.14 chloric acid. Alumina (neutral, 3 g) was added and the toluene was
12 h. Toluene (150 mL) was added and the copper was filtered off.
(‘‘d’’, J ϭ 8.0 Hz, 1 H, 7-H), 8.64 (d, J ϭ 7.8 Hz, 1 H, 2-H), 9.06 distilled off. The residue was poured onto a small column of neutral
(‘‘d’’, J ϭ 9.6 Hz, 1 H, 10-H), 9.09 (d, J ϭ 8.0 Hz, 1 H, 12-H), 9.54 alumina and a 1:1 mixture of toluene and pentane was applied as
(d, J ϭ 9.7 Hz, 1 H, 11-H) ppm. 13C NMR (100 MHz, CDCl3): eluent. Yield: 41 mg (0.14 mmol, 54%) of pure 8a. Rf ϭ 0.21 (silica,
δ ϭ 14.1 (q, C-6Ј), 22.7 (t, C-5Ј), 25.9 (t, C-3Ј), 28.9 (t, C-2Ј), 31.6
toluene/pentane). IR (KBr): ν˜ ϭ 2932 cmϪ1 (w), 1520 (s), 1505 (m),
(t, C-4Ј), 65.8 (t, C-1Ј), 120.7 (s, C-12b), 121.8 (s, C-12c), 122.3 (s, 1334 (s), 844 (w), 823 (w), 809 (m), 749 (m), 705 (w). 1H NMR
C-10b), 122.4 (d, C-3), 122.6 (d, C-5), 123.4 (d, C-10), 123.5 (d, C-
12), 124.8 (s, C-10a), 125.9 (d, C-7), 126.4 (s, C-5a), 127.6 (d, C-
11), 127.6 (d, C-9), 128.2 (s, C-6a), 128.4 (s, C-12a), 128.7 (d, C-8),
(400 MHz, CDCl3): δ ϭ 7.93Ϫ7.97 (m, 1 H, 8-H), 8.00Ϫ8.03 (m,
1 H, 9-H), 7.96 (d, J ϭ 9.0 Hz, 1 H, 4-H), 8.08 (d, J ϭ 8.3 Hz, 1
H, 3-H), 8.19 (d, J ϭ 9.0 Hz, 1 H, 5-H), 8.33 (‘‘d’’, J ϭ 8.3 Hz, 1
129.8 (d, C-2), 130.5 (s, C-1), 131.1 (d, C-4), 133.5 (s, C-3a), 143.9 H, 7-H), 8.67 (s, 1 H, 6-H), 8.72 (d, J ϭ 8.3 Hz, 1 H, 2-H), 9.08
(s, C-6), 167.5 (s, COO) ppm. MS: (EI): m/z (%) ϭ 425 (100) [Mϩ],
(‘‘d’’, J ϭ 8.3 Hz, 1 H, 10-H), 9.19 (d, J ϭ 9.5 Hz, 1 H, 12-H), 9.29
Eur. J. Org. Chem. 2003, 3162Ϫ3166
2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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