Synthesis of Symmetrical Tröger’s Base Analogues
132.48, 132.14, 128.10, 120.26, 65.86, 54.61, 17.52, 16.85 ppm. (300 MHz, [D6]DMSO): δ = 8.00 (d, J = 2.5 Hz, 2 H, 3-H, 9-H),
C19H20Br2N2 (436.19): calcd. C 52.32, H 4.62, N 6.42; found C
51.97, H 4.78, N 6.34.
7.60 (d, J = 2.5 Hz, 2 H, 1-H, 7-H), 4.71 (d, J = 17.9 Hz, 2 H, 6-
H, 12-H), 4.43 (d, J = 18.2 Hz, 2 H, 6-H, 12-H), 4.29 (s, 2 H,
13-H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 145.40, 139.60,
133.29, 131.60, 128.32, 123.04, 64.94, 55.95 ppm. HRMS (ESI):
2,8-Dibromo-1,4,7,10-tetrachloro-6,12-dihydro-5,11-methanodi-
benzo[b,f][1,5]diazocine (11): The crude product was obtained from
2j (7.58 g, 31.5 mmol), paraformaldehyde (1.90 g, 63.3 mmol) and
trifluoroacetic acid (70 mL) after basification with aqueous ammo-
nia and evaporation of the extraction solvent (dichloromethane).
The crude product was washed with a dichloromethane/hexane
(1:2) mixture to give 11 as a yellowish solid in 44% yield (3.55 g),
calcd. for C15H11Cl2N4O4 ([M + H]+) 381.0152; found 381.0155.
+
2,8-Dibromo-4,10-dinitro-6,12-dihydro-5,11-methanodibenzo[b,f]-
[1,5]diazocine (15): The product was obtained from 5 (0.5 g,
1.3 mmol), potassium nitrate (0.28 g, 2.8 mmol) and sulfuric acid
(20 mL) as a yellow solid in 92% yield (0.57 g). The analytical sam-
ple was obtained by precipitation from hot DMSO solution with
1
m.p. 266–267 °C. H NMR (300 MHz, [D6]DMSO): δ = 7.86 (s, 2
H, 3-H, 9-H), 4.55 (d, JH,H = 17.6 Hz, 2 H, 6-H, 12-H), 4.30 (s, 2 water and washing with acetone, m.p. 288–291 °C. 1H NMR
H, 13-H), 4.24 (d, JH,H = 17.8 Hz, 2 H, 6-H, 12-H) ppm. 13C NMR
(75 MHz, [D6]DMSO): δ = 143.99, 131.74, 130.76, 130.17, 128.04,
117.18, 64.46, 54.03 ppm. C15H8Br2Cl4N2 (517.85): calcd. C 34.79,
H 1.56, N 5.41; found C 34.58, H 1.51, N 5.40.
(300 MHz, [D6]DMSO): δ = 8.09 (d, JH,H = 2.3 Hz, 2 H, 3-H, 9-
H), 7.70 (d, JH,H = 2.3 Hz, 2 H, 1-H, 7-H), 4.71 (d, JH,H = 18.0 Hz,
2 H, 6-H, 12-H), 4.42 (d, JH,H = 18.0 Hz, 2 H, 6-H, 12-H), 4.29 (s,
2 H, 13-H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 145.51,
139.97, 134.48, 133.58, 125.72, 115.95, 64.88, 55.78 ppm.
C15H10Br2N4O4 (470.08): calcd. C 38.33, H 2.14, N 11.92; found C
38.12, H 2.13, N 12.02.
1,2,4,7,8,10-Hexabromo-6,12-dihydro-5,11-methanodibenzo[b,f]-
[1,5]diazocine (12): The crude product was obtained from 2k
(1.50 g, 4.6 mmol), paraformaldehyde (0.27 g, 9.1 mmol) and tri-
fluoroacetic acid (10 mL) after basification with aqueous ammonia
and evaporation of the extraction solvent (dichloromethane). The
crude product was washed with a dichloromethane/methanol
(100:1) mixture. The filtrate was further purified by column
chromatography (dichloromethane/methanol 100:1). The solids
were combined to obtain pure product as a white solid in 74%
2,8-Dimethyl-4,10-dinitro-6,12-dihydro-5,11-methanodibenzo[b,f]-
[1,5]diazocine (17): The product was obtained from 1 (0.52 g,
2.1 mmol), potassium nitrate (0.60 g, 4.4 mmol) and sulfuric acid
(45 mL) as an orange solid in 58% yield (0.41 g). The analytical
sample was obtained by washing with hot acetone, m.p. 229–232 °C
1
(ref.[16a] m.p. 242–243 °C). H NMR (300 MHz, [D6]DMSO): δ =
1
yield (1.17 g), m.p. 306–309 °C. H NMR (300 MHz, [D6]DMSO):
7.65 (d, JH,H = 1.4 Hz, 2 H), 7.23 (d, JH,H = 1.2 Hz, 2 H), 4.66 (d,
JH,H = 17.7 Hz, 2 H), 4.33 (d, JH,H = 17.8 Hz, 2 H), 4.26 (s, 2 H),
δ = 8.01 (s, 2 H, 3-H, 9-H), 4.46 (d, JH,H = 17.7 Hz, 2 H, 6-H, 12-
H), 4.30 (s, 2 H, 13-H), 4.22 (d, JH,H = 17.6 Hz, 2 H, 6-H, 12- 2.26 (s, 6 H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 144.68,
H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 145.23, 134.56,
132.45, 124.06, 120.48, 119.53, 64.60, 57.55 ppm. C15H8Br6N2 HRMS (ESI): calcd. for C17H17N4O4+ ([M + H]+) 341.1244; found
138.38, 134.35, 132.36, 130.75, 123.41, 65.63, 56.26, 19.99 ppm.
(695.67): calcd. C 25.90, H 1.16, N 4.03; found C 26.15, H 1.14, N
3.99.
341.1248.
2,4,8,10-Tetrabromo-1,7-dinitro-6,12-dihydro-5,11-methanodi-
benzo[b,f][1,5]diazocine (18): The product was obtained from
8 (1.00 g, 1.9 mmol), potassium nitrate (0.41 g, 4.1 mmol) and
sulfuric acid (15 mL) as a beige solid in 93% yield (1.09 g). The
analytical sample was obtained by washing with hot acetone, m.p.
General Procedure for the Synthesis of Dinitro-Substituted Tröger’s
Base Derivatives 13–15, 17–19, 22 and 23: Tröger’s base 1 or 3–
12[15b] (1 equiv.) was dissolved in the smallest volume of concen-
trated sulfuric acid, and potassium nitrate (2.1–2.2 equiv.) was
slowly added. The resulting mixture was stirred at room tempera-
ture for 2 h and then poured into crushed ice. The pH was adjusted
to 8–9 by addition of aqueous ammonia. The precipitated solid was
collected by filtration, washed with water and ether and dried in
vacuo to afford the dinitro-substituted Tröger’s base in good yield.
1
263–266 °C. H NMR [300 MHz, [D6]DMSO + acetone (30:1)]: δ
= 8.20 (s, 2 H, 3-H, 9-H), 4.70 (d, JH,H = 17.4 Hz, 2 H, 6-H, 12-
H), 4.44 (s, 2 H, 13-H), 4.16 (d, JH,H = 17.5 Hz, 2 H, 6-H, 12-
H) ppm. 13C NMR [75 MHz, [D6]DMSO + acetone (30:1)]: δ =
147.89, 144.88, 135.38, 124.46, 123.27, 108.27, 64.51, 51.03 ppm.
–
HRMS (ESI): calcd. for C15H7Br4N4O4 ([M – H]–) 626.7165;
2,8-Difluoro-4,10-dinitro-6,12-dihydro-5,11-methanodibenzo[b,f]-
[1,5]diazocine (13): The product was obtained from 3 (1.00 g,
3.9 mmol), potassium nitrate (0.82 g, 8.1 mmol) and sulfuric acid
(50 mL) as a yellow solid in 75% yield (1.00 g). The analytical sam-
ple was obtained by washing with hot acetone, m.p. 242–243 °C.
1H NMR (300 MHz, [D6]DMSO): δ = 7.84 (dd, JH,F = 8.4, JH,H
= 3.0 Hz, 2 H, 3-H, 9-H), 7.44 (dd, JH,F = 8.5, JH,H = 3.0 Hz, 2
H, 1-H, 7-H), 4.71 (d, JH,H = 18.1 Hz, 2 H, 6-H, 12-H), 4.42 (d,
JH,H = 18.2 Hz, 2 H, 6-H, 12-H), 4.28 (s, 2 H, 13-H) ppm. 13C
NMR (75 MHz, [D6]DMSO): δ = 157.24 (d, JC,F = 245.5 Hz),
145.36 (d, JC,F = 9.2 Hz), 137.17 (d, JC,F = 3.0 Hz), 133.46 (d, JC,F
= 7.6 Hz), 118.66 (d, JC,F = 22.4 Hz), 110.85 (d, JC,F = 27.9 Hz),
65.14 (s), 56.22 (s) ppm. 19F NMR (282 MHz, [D6]DMSO): δ =
–114.63 (dd, JF,H = 8.4, 8.4 Hz) ppm. HRMS (ESI): calcd. for
found 626.7198.
2,8-Dibromo-4,10-dichloro-1,7-dinitro-6,12-dihydro-5,11-methanodi-
benzo[b,f][1,5]diazocine (19): The product was obtained from
9 (0.50 g, 1.1 mmol), potassium nitrate (0.25 g, 2.5 mmol) and
sulfuric acid (10 mL) as a beige solid in 85% yield (0.51 g). The
analytical sample was obtained by washing with hot acetone, m.p.
317–319 °C. 1H NMR (300 MHz, [D6]DMSO): δ = 8.06 (s, 2 H, 3-
H, 9-H), 4.72 (d, JH,H = 17.3 Hz, 2 H, 6-H, 12-H), 4.43 (s, 2 H,
13-H), 4.13 (d, JH,H = 17.4 Hz, 2 H, 6-H, 12-H) ppm. 13C NMR
(75 MHz, [D6]DMSO): δ = 147.43, 143.61, 132.55, 132.26, 124.43,
1 0 7 . 9 7 , 6 4 . 3 9 , 5 0 . 5 4 p p m . H R M S ( E S I ) : c a l c d . fo r
C15H7Br2Cl2N4O4 ([M – H]–) 536.8196; found 536.8226.
–
2,8-Dibromo-1,4,7,10-tetramethyl-3,9-dinitro-6,12-dihydro-5,11-
methanodibenzo[b,f][1,5]diazocine (22): The product was obtained
from 10 (1.00 g, 2.3 mmol), potassium nitrate (0.49 g, 4.9 mmol)
and sulfuric acid (22 mL) as a yellow solid in 58% yield (0.70 g).
+
C15H11F2N4O4 ([M + H]+) 349.0743; found 349.0747.
2,8-Dichloro-4,10-dinitro-6,12-dihydro-5,11-methanodibenzo[b,f]-
[1,5]diazocine (14): The product was obtained from 4 (1.20 g,
4.1 mmol), potassium nitrate (0.88 g, 8.7 mmol) and sulfuric acid
(50 mL) as a yellow solid in 93% yield (1.47 g). The analytical sam-
ple was obtained by precipitation from hot DMSO solution with
water and washing with acetone, m.p. 309–312 °C. 1H NMR
1
Decomp. without melting. H NMR (300 MHz, [D6]DMSO): δ =
4.55 (d, JH,H = 17.4 Hz, 2 H, 6-H, 12-H), 4.21 (s, 2 H, 13-H), 4.03
(d, JH,H = 17.5 Hz, 2 H, 6-H, 12-H), 2.32 (s, 6 H, HC4,10-CH3), 2.23
(s, 6 H, HC1,7-CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 150.93,
Eur. J. Org. Chem. 2012, 7066–7074
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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