T. Mas, C. Pardo, F. Salort, J. Elguero, M. R. Torres
FULL PAPER
NH) ppm. 13C NMR ([D6]DMSO): δ ϭ 20.22, 113.75, 115.57,
116.06, 116.74, 120.83, 121.27, 123.33, 126.50, 127.78, 128.67,
133.05, 134.30, 135.13, 135.56, 147.59, 155.40, 166.01, 167.87 ppm.
C21H19N5O4 (405.4): calcd. C 62.22, H 4.72, N 17.27; found C
62.20, H 4.60, N 17.39.
N-(2-Amino-5-methylbenzyl)-NЈ-(2-amino-5-nitrobenzyl)-p-phenyl-
enediamine (14): 10 borane-dimethylsulfide (2.1 mL; 20.7 mmol)
was added dropwise to a suspension of amide 13 (700 mg;
1.73 mmol) in anhydrous THF (15 mL) at 0 °C under an argon
atmosphere. The suspension was refluxed for 20 h and cooled to
room temperature. A 0.7 solution of HCl in methanol (15 mL)
was then added dropwise, the reaction mixture refluxed for 1 h, and
the solvents evaporated under reduced pressure. Water (50 mL) was
added to the residue, the resulting solution adjusted to pH 11 with
25% aqueous ammonia solution, and extracted with CH2Cl2 (3 ϫ
50 mL). The organic layer was washed with water (50 mL), dried
with anhydrous MgSO4, and the solvents evaporated under reduced
pressure. Flash chromatography (eluent hexane/ethyl acetate 1:1)
afforded the pure amine 14 (620 mg). Yield 95%. M.p. 173Ϫ174
°C. IR (KBr): ν˜ ϭ 3481, 3452, 3406 and 3368 (νNH), 1636, 1522
(νNO asymm.), 1306 (νNO symm.), 1286, 824 cmϪ1 1H NMR
.
2
2
([D6]DMSO): δ ϭ 2.11 (s, 3 H, CH3), 3.92 (d, J ϭ 5.9 Hz, 2 H,
CH2), 3.99 (d, J ϭ 5.9 Hz, 2 H, CH2), 5.09 (t, J ϭ 5.9 Hz, 1 H,
NH), 5.46 (t, J ϭ 5.9 Hz, 1 H, NH), 6.39Ϫ6.46 (AAЈBBЈ, 4 H, 2-
H, 3-H, 5-H and 6-H), 6.47 (br. s, 2 H, NH2), 6.53 (d, J ϭ 8.1 Hz,
1 H, 3Ј-H), 6.60 (br. s, 2 H, NH2), 6.67 (d, J ϭ 8.8 Hz, 1 H, 3"-H),
6.75 (br. d, J ϭ 8.1, 1 H, 4Ј-H), 6.89 (br. s, 1 H, 6Ј-H), 7.87 (dd,
J ϭ 9.0, 2.7 Hz, 1 H, 4"-H), 7.99 (d, J ϭ 2.7 Hz, 1 H, 6"-H) ppm.
13C NMR ([D6]DMSO): δ ϭ 20.22, 44.03, 45.48, 113.15, 113.87,
114.10, 114.88, 122.57, 123.36, 124.01, 124.20, 124.28, 127.64,
128.84, 135.99, 139.86, 140.85, 143.90, 153.17 ppm. C21H23N5O2
(377.4): calcd. C 66.83, H 6.14, N 18.55; found C 66.76, H 6.10,
N 18.64.
Figure 2. The unit cell of 17b
reaction was allowed to reach room temperature and the mixture
stirred overnight. The precipitate of dicyclohexylurea was then fil-
tered off, washed with dichloromethane, and ethyl acetate (300 mL)
added to the filtrate. The resulting solution was washed with satu-
rated aqueous NaHCO3 (3 ϫ 100 mL), water (10 ϫ 100 mL), dried
with anhydrous MgSO4, and the solvents evaporated under reduced
2-Methyl-11-nitro-5,17:8,14-dimethano-5,8,14,17-tetraaza-5,6,7,8,
pressure. Flash chromatography (eluent hexane/ethyl acetate 6:4) 13,14,17,18-octahydrodibenzo[e,eЈ]benzo[1,2-a:3,4-aЈ]dicyclo-
octene (5). Method A: 35% Aqueous formaldehyde (0.6 mL) and
yielded the pure amide 12 (5.28 g). Yield 56%. M.p. 164Ϫ165 °C.
IR (KBr): ν˜ ϭ 3416 and 3288 (νNH), 1639 (νCO), 1516, 1425, 1256, 35% HCl (0.6 mL) were added successively to a suspension of the
1
1207, 822 cmϪ1. H NMR ([D6]DMSO): δ ϭ 2.20 (s, 3 H, CH3), diamine 14 (200 mg; 0.53 mmol) in ethanol (9 mL) at room tem-
4.88 (s, 2 H, NH2), 6.03 (s, 2 H, NH2), 6.53 (AAЈ, 2 H, 2Ј-H and perature under argon. The mixture was stirred at 90 °C for 24 h,
6Ј-H), 6.64 (d, J ϭ 8.3 Hz, 1 H, 3-H), 6.99 (dd, J ϭ 8.3, 1.5 Hz, 1 cooled to room temperature and poured inzo 17 mL of water. The
H, 4-H), 7.31 (BBЈ, 2 H, 3Ј-H and 5Ј-H), 7.38 (d, J ϭ 1.5 Hz, 1 H,
6-H), 9.60 (s, 1 H, NH) ppm. 13C NMR ([D6]DMSO): δ ϭ 20.20, extracted with dichloromethane (3 ϫ 50 mL). The organic layer
113.81, 116.19, 116.58, 122.53, 123.26, 128.38, 128.51, 132.51,
was washed with saturated solutions of NaHCO3 and NaCl, dried
145.11, 147.28, 167.35 ppm. C14H15N3O (241.3): calcd. C 69.69, H with anhydrous MgSO4, filtered and the solvents were evaporated
solution was adjusted to pH 11 with 25% aqueous ammonia and
6.27, N 17.41; found C 69.78, H 6.03, N 17.55.
under reduced pressure. Flash chromatography (eluent hexane/ethyl
acetate, 1:9) yielded first the anti isomer 5b (12% yield) and then
the syn isomer 5a (10% yield). Method B: As for Method A, but
with heating at 50 °C for 24 h. Only anti 5b was obtained (10%
yield). Method C: A suspension of the diamine 14 (0.40 mmol) and
hexamethylenetetramine (0.8 mmol) in trifluoroacetic acid (1.5 mL)
was stirred under argon at room temperature for 24 h, by which
time the suspension had cleared. Trifluoroacetic acid was removed
under reduced pressure, water was added to the residue and the
solution adjusted to pH 11 with 25% aqueous ammonia. This solu-
tion was extracted with CHCl3 (3 ϫ 50 mL), the organic layer dried
with anhydrous MgSO4, filtered and the solvents were evaporated
N-(2-Amino-5-methylbenzoyl)-NЈ-(2-amino-5-nitrobenzoyl)-p-phen-
ylenediamine (13): Amide 12 (400 mg; 1.66 mmol) was added in
small portions to a suspension of 6-nitroisatoic anhydride (9)
(448 mg; 2.16 mmol) in anhydrous THF (4.5 mL) at room tempera-
ture under an argon atmosphere. The solution was refluxed for 6 h,
poured into saturated aqueous NaHCO3 (50 mL) and extracted
with ethyl acetate (3 ϫ 50 mL). The organic layer was washed with
water (50 mL), dried with anhydrous MgSO4, and the solvents eva-
porated under reduced pressure. Crystallization from ethyl acetate
yielded the pure amide 13 (504 mg). Yield 75%. M.p. 288Ϫ289 °C.
IR (KBr): ν˜ ϭ 3458, 3371 and 3332 (νNH), 1645 and 1612 (νCO),
1
under reduced pressure. TLC and H NMR of the residue showed
that there were no traces of 5.
1520 (νNO asymm.), 1320 (νNO symm.), 820 cmϪ1
.
1H NMR
2
2
([D6]DMSO): δ ϭ 2.22 (s, 3 H, CH3), 6.10 (br. s, 2 H, NH2), 6.67
(d, J ϭ 8.3 Hz, 1 H, 3Ј-H), 6.85 (d, J ϭ 9.3 Hz, 1 H, 3"-H), 7.03 N,NЈ-Bis(2-amino-5-nitrobenzoyl)-p-phenylenediamine (15): 6-Nitro-
(br. d, J ϭ 8.3 Hz, 1 H, 4Ј-H), 7.43 (br. s, 1 H, 6Ј-H), 7.67 (m, 4 isatoic anhydride (9) (1.92 g; 9.2 mmol) was added in small por-
H, 2-H, 3-H, 5-H and 6-H), 8.08 (dd, J ϭ 9.3, 2.5 Hz, 1 H, 4"-H),
tions to a suspension of p-phenylenediamine (8) (482 mg;
8.62 (d, J ϭ 2.5 Hz, 1 H, 6"-H), 9.98 (s, 1 H, NH), 10.42 (s, 1 H, 4.5 mmol) in anhydrous THF (16 mL) at room temperature under
1102
2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2004, 1097Ϫ1104