1
306
C. Pardo, C. Pirat and J. Elguero
Vol 44
amide 7. The crude was chromatographed using as eluent ethyl
acetate/hexane 9:1. Pale brown pure amide was obtained (98 mg,
yield 53%). The reaction was repeated starting from 2.72 mmol
C, 85.68; H, 5.63; N, 8.69. Found: C, 85.86; H, 5.43; N, 8.77.
HRMS(EI) Calcd. for C H N : 322.14699. Found: 322.14653.
2
3
18
2
6H-12H-Dipyrido[2,3-b:2',3'-f][1,5]diazocine-5,11-dione (10).
(
546 mg) of ester 6 and 492 mg of amide pure enough to
O
H
continue the synthesis was obtained (yield 100%). Mp: > 300 ºC
4
N
-
1
4a
N
(dec.). IR (KBr) ꢀ (cm ): 3167, 3053, 2922, 1655, 1387, 1308,
3
2
1
1
267, 1236, 752. H RMN (DMSO-d ) ꢁ (ppm): 7.46 (td, 1H,
12a
N
6
3
4
3
N
Japp = 6.7 Hz, J = 1.3 Hz, H-2), 7.50 (td, 1H, J = 6.5 Hz,
1
2,4
app
4
3
H
O
J1,3 = 1.3 Hz, H-3), 7.65 (s, 1H, H-5), 7.85 (d, 1H, J = 7.4 Hz,
3,4
3
Ester 9 (0.921 mmol, 140 mg) was added to 2.43 mmol (97 mg)
of 60% sodium hydride in suspension in oil covered by anhydrous
THF. The resulting suspension was refluxed 24 h and then
acidified with 5% hydrochloric acid. By adding water, bis-amide
10 precipitates: 25 mg, 25% yield. A second reaction starting from
3.72 mmol (566 mg) of 9 affords 128 mg of pure 10, yield 29%.
Mp: > 300 ºC (dec.). IR (KBr) ꢀ (cm ): 3238, 3177, 3057, 2922,
655, 1589, 1576, 1481, 1429, 1385. H RMN (DMSO-d ) ꢁ
6
(ppm): 7.34 (dd, 1H, J =7.7 Hz, J = 4.8 Hz, H-3), 7.86 (dd,
3,4 2,3
H-4), 7.90 (d, 1H, J = 7.3 Hz, H-1), 7.95 (s, 1H, H-8(16)),
1,2
13
1
1
1
1
7
0.50 (s, 1H, NH). C RMN (DMSO-d ) ꢁ (ppm): 124.02 (C-5),
6
26.77 (C-2), 127.37 (C-4), 127.69 (C-3), 127.86 (C-8(16)),
27.93 (C-1), 131.17 (C-16a), 131.73 (C-4a), 133.12 (C-5a),
33.36 (C-15a), 169.56 (CO). Anal. Calcd. for C H N O : C,
2
2
14
2
2
8.09; H, 4.17; N, 8.28.Found: C, 77.88; H, 4.33; N, 8.30.
-1
6H-7H-14H-15H-Dinaphtho[2,3-b:2',3'-f][1,5]diazocine (8).
1
1
H
N
3
3
1
4
16
5
1
6a
2
3
3
4
3
1
5a
1
H, J = 7.7 Hz, J = 1.8 Hz, H-4), 8.47 (dd, 1H, J = 4.8 Hz,
3,4 2,4 2,3
2,4 = 1.8 Hz, H-2), 10.94 (bs, 1H, NH). C RMN (DMSO-d
5
a
4
13
4
a
J
) ꢁ
6
N
H
(ppm): 123.05 (C-3), 127.64 (C-4a), 138.35 (C-4), 147.11 (C-
1
6
2a), 150.74 (C-2), 167.50 (CO). Anal. Calcd. for C H N O : C,
12 8 4 2
0.00; H, 3.36; N, 23.32. Found: C, 59.87; H, 3.21; N, 23.57.
To 0.176 mmol (60 mg) of bis-amide 7 was added first 1.47
mL of anhydrous THF and then slowly and at 0 ºC, 1.179 mmol
118 μL) of 10 M BH SMe . The mixture is refluxed for 17 h
5
H-6H-11H-12H-Dipyrido[2,3-b:2',3'-f][1,5]diazocine (11).
(
3
2
resulting in a transparent solution. 6 M hydrochloric acid at 0 ºC
was added to destroy the borane, the solution was stirred 3 h and
H
4
N
4
a
N
3
2
1
5 M ammonium hydroxide was added at 0 ºC until the solution
1
2a
becomes basic. Then, it was extracted by dichloromethane (3
times 10 mL), the organic layer is washed with water and dried
N
1
N
H
over anhydrous MgSO . After the solvent was evaporated, 58
4
mg of bis-amine 8 almost pure was obtained and used as such in
the following reaction (attempts to purify the compound by
column chromatography result in partial decomposition). Yield
Careful addition of 0.556 mmol (55.6 μL) of 10 M BH SMe
3
2
to a solution of 0.083 mmol (20 mg) of bis-amide 10 in 1 mL of
anhydrous THF and then 17 h reflux of the resulting solution
results in a transparent solution. The borane in excess is
destroyed by treating the solution with 6 M hydrochloric acid.
Then the stirring is maintained for 3 h, 15 M ammonium
hydroxide is added at 0 ºC till basic pH. The solution is
extracted with dichloromethane (3 times 10 mL), the organic
1
1
1
00%. Mp 275-277 ºC. H RMN ( DMSO-d ) ꢁ (ppm): 6.31 (bt,
6
3
3
H, J = 6.9 Hz, NH), 6.91 (s, 1H, H-5), 7.08 (td, 1H, J = 7.4
Hz, J2 = 1.5 Hz, H-2), 7.23 (td, 1H, J = 7.4 Hz, J = 1.5 Hz,
H-3), 7.44 (bd, 1H, J = 8.6 Hz, H-4), 7.54 (bs, 1H, H-8(16)),
.62 (bd, 1H, J1,2 = 8.6 Hz, H-1). HRMS(EI) Calcd. for
4
3
4
,4
1,3
3
3,4
3
7
C H N : 310.14700. Found: 310.14721.
22
18
2
layer is washed with water and dried over anhydrous MgSO . By
4
7
H-15H-6,14-Methanodinaphtho[2,3-b:2',3'-f][1,5]diazo-
evaporation of the solvent, 11 mg of the bis-amine 11 is
obtained that is pure enough to be used without further
cine (3).
1
3
H
7
x
purification. H RMN (DMSO-d
6
) ꢁ (ppm): 6.52 (dd., 1H, J3,4
=
H
n
3
3
7
.1 Hz, J = 4.9, H-3), 6.58 (bt, J = 8.5 Hz,1H, NH), 7.27 (dd,
1H, J3,4 = 7.1 Hz, J =1.7 Hz, H-4), 7.84 (dd, 1H, J2,3 = 4.9
Hz, J2,4 = 1.7 Hz, H-2). HRMS(EI) Calcd. for C H N :
9
2
8
5
4
1
2,3
N
8
a
7a
3a
13
4a
3
4
3
1
0
1
3
5
a
2,4
1
17
4
1
5a
1
2
12 12
4
15
1
2a
16a
N
1
16
212.10620. Found: 212.10833.
H
n
Hx
Acknowledgement. This work has been financed by the
Spanish Ministry of Education and Science (Project No.
BQU2003-07793-C02-01
To 0.187 mmol (58 mg) of bis-amine 8 were added, under Ar
atmosphere, 2.3 mmol (157 μl) of 35-40% formaldehyde, 1.5
mL of anhydrous ethanol and finally, with care, 393 μL of 6 M
hydrochloric acid. The suspension becomes pale brown with an
increase of the temperature. It was stirred for 64 h at RT. Then
the solution is made basic with 25% ammonium hydroxide.
Water was added and the aqueous solution extracted with
dichloromethane (3 times 10 mL), the organic layer dried over
REFERENCES
[1] Farrar, W. V. J. Appl. Chem. 1964, 389.
[2] Tálas, E.; Margitfalvi, J.; Machytka, D.; Czugler, M.
Tetrahedron Asymm. 1998, 9, 4151.
anhydrous MgSO and the solvent evaporated under reduced
4
pressure. The resulting TB 3 was obtained as a brown solid,
[3] Newkome, G. R.; Paudler, W. W. Contemporary
Heterocyclic Chemistry, John Wiley & Sons, New York, NY, 1982,
pp 107-109.
-1
yield 52 mg, 86%. Mp 213-215 ºC. IR (KBr) ꢀ (cm ): 3422,
924, 2852, 2345, 1499, 1458, 748. Anal. Calcd. for C H N :
2
2
3
18
2