1
584
J. Cairns et al. / Tetrahedron Letters 43 (2002) 1583–1585
Figure 1.
Scheme 3. Conversion of 4 to the pentacyclic dibenzodi-
azepine. Conditions: (i) Ac O, ZnCl , 65°C, 1 h, 68%. (ii)
2
2
−
1
troscopy indicated contained a carbonyl (1670 cm ),
this and absence of an olefinic signal in its NMR
spectrum indicated the product was not 1b. NMR (360
PPA, POCl , 120°C, 45 min, 73%.
3
reflux for 4 h. The warm solution was poured onto ice
and allowed to stand overnight at room temperature.
Ammonium hydroxide was added to neutralise the
solution and 17 g of a green solid collected. Purification
by chromatography on silica (eluent dichloromethane/
methanol, 9/1), followed by conversion to the fumarate
MHz in CDCl ) analysis of the product showed the
3
proton on the 4 position, l 3.48 (q, 4ax, J=7.2 Hz), of
the piperidinyl ring was now adjacent to a nitrogen and
a large coupling with the proton at 3, indicating trans
stereochemistry at the ring fusion. The product was
identified as trans-5-(2-aminophenyl)-1,3,4,4a,5,10a-
hexahydro-2-methylbenzo[b][1,6]naphthyridin-10(2H)-
one 4. A mechanism for the rearrangement is shown in
Scheme 2: the imine function is rapidly hydrolysed
under acidic conditions opening the dibenzodiazepine
ring and an intramolecular Michael addition (6-endo-
trig) affording 4 follows. N-Acetylation of 4 followed
by cyclisation under Bischler–Napieralski conditions
afforded the novel pentacyclic compound 3,9-dimethyl-
salt and crystallisation from methanol–ether afforded
1
3
.38 g (12.3% yield) of 4 fumarate salt. H NMR (200
MHz, DMSO-d ): l 7.75 (d, 1H, J=7 Hz), 7.25 (t, 1H,
6
J=8 Hz), 7.02 (t, 1H, J=8 Hz), 6.90 (d, 1H, J=9 Hz),
6
1
.87–6.60 (m, 3H), 6.60 (s, 2H, fumaric acid), 6.10 (d,
H, J=8 Hz), 4.50–5.70 (broad peak, 4H), 3.70–3.50
(
2
m, 1H), 3.45–3.20 (m, 2H), 2.85 (d, 1H, J=11 Hz),
.32 (s, 3H), 2.15–1.90 (m, 2H), 1.70–1.50 (m, 2H).
Anal. calcd for C H N O : C, 65.24; H, 5.95; N, 9.92.
23
25
3
5
1
,2,3,4,4a,14c - hexahydro - 3,10,14b - triaza - benzo[4,5]-
Found C, 65.22; H, 6.08; N, 9.83. IR 0.5% KBr disc
7
cyclohepta[1,2,3-de]anthracene-5-one 5 (Scheme 3).
−1
−1
3
(
300–3500 cm (two peaks, NH stretch), 1670 cm
−
1
−1
carbonyl), 1615 cm and 1492 cm (Ar-H). Melting
The same demethylation conditions were applied to
point=197°C.
11-(1,2,5,6-tetrahydro-1-methyl-4-pyridinyl)-5-methyl-
5
H-dibenzo[b,e][1,4]diazepine 6. No infrared absorp-
4
[
- Amino - 5,13 - diaza - 13 - methyl - bicyclo[3.3.1]nonan-
6,7,8-k,l]acridine 7. 11-(1,2,5,6-Tetrahydro-1-methyl-
4-pyridinyl)-5-methyl-5H-dibenzo[b,e][1,4]diazepine
0.5 g, 1.65 mmol) was treated with conc. HBr as
tion was observed in the carbonyl stretch region, indi-
cating the expected hydrolysis-Michael product had not
been formed. H NMR analysis of the product showed
the presence of only six protons attached to aromatic
rings and the piperidine ring still intact but fully satu-
rated, while C contained a total of 13 aromatic
carbons. The product was identified as 4-amino-5,13-
diaza-13-methyl-bicyclo[3.3.1]nonan[6,7,8-k,l]acridine
1
6
(
described above. After chromatography 150 mg of a
1
1
3
red gum was isolated (21% yield). H NMR (360 MHz,
CDCl ): l 8.22 (d, 1H, J=9 Hz), 8.14 (d, 1H, J=9 Hz),
3
7
.71 (dd, 1H, J=8.6, 1.5 Hz), 7.53 (dd, 1H, J=7.9, 1.5
Hz), 7.02 (d, 1H, J=9 Hz), 6.89 (d, 1H, J=9 Hz),
.10–5.40 (br, 2H), 4.13 (m, 1H), 4.02 (t, 1H, J=2.7
Hz), 2.62–2.57 (m, 1H), 2.52–2.40 (m, 2H), 2.27 (s, 3H),
7
, and a mechanism has been tentatively proposed
Scheme 4).
5
(
2
1
.24–2.17 (m, 1H), 1.89–1.82 (m, 1H), 1.65–1.56 (m,
Experimental
13
H). C NMR (50 MHz, CDCl ): l 146.6 (q), 145.1
3
trans-5-(2-Aminophenyl)-1,3,4,4a,5,10a-hexahydro-2-
methylbenzo[b][1,6]naphthyridin-10(2H)-one 4. 11-(1,2,5,
(q), 143.4 (q), 138.9 (q), 130.6 (CH), 128.9 (CH), 126.5
(CH), 125.7 (CH), 125.3 (q), 123.5 (q), 123.0 (CH),
6
-Tetrahydro-1-methyl-3-pyridinyl)-5-methyl-5H-diben-
117.6 (q), 106.8 (CH), 58.4 (NCH), 46.3 (NCH
), 42.5
2
zo[b,e][1,4]diazepine 1 (19.7 g 0.065 mol) was dissolved
(NCH ), 33.1 (CH ), 31.4 (CH ), 28.2 (CH). C H N ,
3
2
2
19 19
3
3
+
in 48% hydrobromic acid (100 cm ) and heated under
EI GC-MS 289 (M ).
Scheme 2. Mechanism of rearrangement of 1. Conditions: conc. HBr, reflux, 4 h, 20%.