Intramolecular [4 + 2] cycloaddition reactions of ketenimines: A new synthesis of benz[b]acridines

Article abstract of DOI:10.1055/s-2002-35234

N-[2-(2-Propenyl)phenyl]-C,C-diphenyl ketenimines undergo a thermally induced intramolecular [4 + 2] cycloaddition to give 5,11,11a,12-tetrahydrobenz[b]acridines, which are converted into the fully aromatic benz[b]acridines by oxidation with Pd/C in refluxing ortho-xylene.

Full text of DOI:10.1055/s-2002-35234

PAPER
2393
Intramolecular [4 + 2] Cycloaddition Reactions of Ketenimines: A New
Synthesis of Benz[b]acridines
Intramolecular [4
+
2]
a
Cycloadditi
t
on Rea
e
c
tions of
K
o
etenimines: A New
A
Synthesis of
B
en
l
z
[
b
]
acr
a
idines jarín,* Angel Vidal, María-Mar Ortín, Fulgencio Tovar
Departamento de Química Orgánica, Facultad de Química, Universidad de Murcia, Campus de Espinardo, 30100 Murcia, Spain
Fax +34(968)364149; E-mail: alajarin@um.es
Received 18 July 2002; revised 24 July 2002
equivalent of diphenylketene led to N-(2-allylphenyl)-
C,C-diphenylketenimine (3), which was used in the next
step without purification due to the hydrolytic sensitivity
of the ketenimine function. Nevertheless, its formation
was established by IR spectroscopy: the reaction mixture
showed a strong absortion around 2000 cm–1 attributable
to the N=C=C grouping. When compound 3 was heated at
130 °C for 16 hours (toluene solution, sealed tube), 6-phe-
nyl-5,11,11a,12-tetrahydrobenz[b]acridine (5) was ob-
tained in a 39% yield, after purification by column
chromatography (Scheme 1).
Abstract: N-[2-(2-Propenyl)phenyl]-C,C-diphenyl
ketenimines
undergo a thermally induced intramolecular [4 + 2] cycloaddition to
give 5,11,11a,12-tetrahydrobenz[b]acridines, which are converted
into the fully aromatic benz[b]acridines by oxidation with Pd/C in
refluxing ortho-xylene.
Key words: azides, acridines, cycloadditions, polycycles, keten-
imines, phosphazenes
Ketenimines have been extensively used in organic syn-
thesis as substrates for the construction of isolated or
fused six-membered heterocycles via inter or intramolec-
ular [4 + 2] cycloaddition reactions,1 where the keten-
imines are able to play different roles. First, these
heterocumulenes can serve as the 2 -electron components
by using either their C=N or C=C bonds. Secondly, keten-
imines may act in [4 + 2] cycloadditions as 2-azadienes,
reacting across the dienic system formed by their C=N
bond and a conjugated C=C bond from a substituent on
the nitrogen atom [N-vinyl (or aryl) ketenimines], or as an
all-carbon diene, using their cumulative C=C bond and a
conjugated C=C bond on the sp2 carbon terminus [C-vinyl
(or aryl) ketenimines]. We have applied this methodology
to the synthesis of benzo[de][1,6]naphthyridines2 and py-
rido[2,3,4-de]quinazolines2 (ketenimine as 2-azadiene),
11-aryl-6-phenyl-6,11-dihydrobenzimidazo[1,2-b]isoqui-
nolines3 (ketenimine as an all-carbon diene) and 3-aryl-
3,4-dihydropyrido[1,2-a]benzimidazoles4 (ketenimine as
2 -electron component via its C=C bond).
Compound 5 was characterized by its analytical and spec-
troscopic data. In this respect, its 1H and 13C NMR spectra
indicated that the original allyl side-chain now appears as
a three sp3-carbon chain, with one central methine group
flanked by two methylenes. In the 1H NMR the four me-
thylene protons were observed as a multiplet at = 2.73–
3.10, and the H-C11a proton also appears as a multiplet at
= 3.25–3.45. The 13C NMR spectrum shows the signals
due to the two methylene carbon atoms, C11 and C12, at
= 33.1 and 36.1, and the methine carbon C11a at
= 34.6.
We believe that the conversion 3 5 involves an intramo-
lecular [4 + 2] cycloaddition, in which the ketenimine
fragment acts as an all-carbon diene, followed by H shift.
The 5,11,11a,12-tetrahydrobenz[b]acridine 5 was oxi-
dized in refluxing ortho-xylene in the presence of Pd/C to
give the fully aromatic compound 6 in almost quantitative
yield (Scheme 1). However, this method could not be ap-
plied to the preparation of 6-alkyl substituted analogues of
6, as the thermal treatment of C-alkyl-C-phenyl keten-
imines (prepared from 2 and alkyl phenyl ketenes) yielded
only intractable mixtures.
As a further application we report herein a new general
synthesis of the benz[b]acridine ring system,5 based on an
intramolecular [4 + 2] cycloaddition reaction on N-[2-(2-
propenyl)phenyl]-C,C-diphenyl ketenimines, in which
the ketenimine function acts as an all-carbon diene and the
C=C bond of the allyl side-chain plays the role of the di-
enophile.
Staudinger reaction6 of 2-allyl-1-azidobenzene7 (1) with
triphenylphosphane, in toluene solution at room tempera-
ture, yielded the corresponding triphenylphosphazene 2.
The transformation 1 2 was completed in less than 1
hour, as followed by IR (disappearance of the azide vibra-
tion near 2100 cm–1) and 31P NMR.8 The reaction of tri-
phenylphosphazene 2 in the same reaction flask with one
Next we applied this synthetic methodology to the prepa-
ration of a series of 6-phenylbenz[b]acridines substituted
at C11. Thus, the Wittig reaction of 2-azido-
phenylacetaldehyde7 7 with several benzyltriphenylphos-
phonium bromides 8 in the presence of potassium
carbonate and dibenzo-18-crown-6, in dichloromethane at
room temperature, provided 1-aryl-3-(2-azidophenyl)pro-
penes 9 in moderate to good yields (Table 1). Azides 9
were converted into the corresponding ketenimines 10 by
sequential treatment with triphenylphosphane and diphe-
nylketene. When compounds 10 were heated at 130 °C for
16 hours, in toluene solution in a sealed tube, and the
crude material resulting from this thermal treatment9 sub-
sequently heated in refluxing ortho-xylene in the presence
Synthesis 2002, No. 16, Print: 14 11 2002.
Art Id.1437-210X,E;2002,0,16,2393,2398,ftx,en;Z10502SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

2394
M. Alajarín et al.
PAPER
1) PPh3
toluene, r.t., 1 h
2) Ph2C=C=O
toluene, r.t., 30 min
N3
N PPh3
1
2
3) 130°C
H
toluene, sealed tube, 16 h
(39%)
N
N C C
Ph
Ph
3
4
1
12
N
11
10% Pd/C
o-xylene, reflux, 2 h
(98%)
N
H
6
Ph
4
Ph
5
6
Scheme 1
of Pd/C the 11-aryl-6-phenylbenz[b]acridines 11 were is representative of a new heterocyclic system. Its struc-
isolated and purified by column chromatography ture was unambiguously deduced from its spectroscopic
(Scheme 2). Compounds 11 were obtained in acceptable and analytical data. The absence of a low-field signal cor-
global yields (20–50%) for the conversion 9 11, four re- responding to the H–C12 proton of the benz[b]acridines
action steps in a one-pot process (Table 1).
11 in the 1H NMR spectrum of 12 is particularly signifi-
cant for assigning its structure.
The hexacyclic 9-phenyl-15H-benzo[i]quino[4,3,2-
kl]acridine (12) accompanied compound 11d in the mix- The formation of the benzo[i]quino[4,3,2-kl]acridine 12
ture resulting from the thermal treatment and subsequent during the preparation of 11d can be understood as result-
oxidation of ketenimine 10d (Ar = 2-O2N-C6H4). In fact, ing from the reduction of the nitro group of 11d to give the
12 was the major reaction product (36% yield vs. 20% 11-aminophenyl derivative 13, which by means of an in-
yield of 11d). To the best of our knowledge, compound 12 tramolecular amination process of the pyridine ring and a
Ar
Ar-CH2PPh3Br (8)
K2CO3, dibenzo-18-crown-6
CHO
CH2Cl2, r.t., 16 h
(52-80%)
N3
N3
7
9
1) PPh3
toluene, r.t., 1 h
2) Ph2C=C=O
toluene, r.t., 30
min
Ar
Ar
3) 130°C
toluene, sealed tube, 16 h
Ph
N C C
Ph
4) 10% Pd/C
N
o-xylene, reflux, 5 h
Ph
(20-50%)
11
10
Scheme 2
Synthesis 2002, No. 16, 2393–2398 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Intramolecular [4 + 2] Cycloaddition Reactions of Ketenimines: A New Synthesis of Benz[b]acridines
2395
Table 1 1-Aryl-3-(2-azidophenyl)propenes 9 and 11-Aryl-6-phe-
nylbenz[b]acridines 11
Alternatively when a solution of the 11-(2-nitrophe-
nyl)benz[b]acridine 11d in a mixture of triethylphosphite
and ortho-xylene was heated at reflux temperature for 16
hours a 30% yield of compound 12 was obtained, as ex-
pected for a nitrene insertion10 into the 4-pyridyl C–H
bond (Scheme 4).
Entry
Ar
Yield of 9 (%)
Yield of 11 (%)a
a
b
c
d
e
f
2-Br-C6H4
4-Br-C6H4
4-Me-C6H4
2-O2N-C6H4
4-O2N-C6H4
4-MeO-C6H4
74
55
52
71
80
35
40
27
50
20
33
36
In conclusion we have developed a general approach to
the tetracyclic benz[b]acridine core, based on a new in-
tramolecular [4 + 2] cycloaddition in C,C-diphenylketen-
imines, which in turn are easily accessible from
adequately substituted azidobenzenes. From these com-
pounds, four consecutive reaction steps are carried out in
one-pot, and the final products are obtained in acceptable
yields.
a Global yields of the conversion 9 11
All mps were determined on a Kofler hot-plate mp apparatus and
are uncorrected. IR spectra were obtained as Nujol emulsions or
films on a Nicolet Impact 400 spectrophotometer. NMR spectra
were recorded on a Bruker AC-200 or a Varian Unity 300 spectro-
meter, using SiMe4 as the internal standard. Mass spectra were re-
corded on a Hewlett–Packard 5993C spectrometer. Microanalyses
were performed on a Carlo Erba EA-1108 instrument. 2-Allyl-1-
azidobenzene7 (1), 2-azidophenylacetaldehyde7 (7) and
diphenylketene11 were prepared according to literature procedures.
Benzyltriphenylphosphonium bromides 8 were prepared from the
corresponding commercially available benzylbromides following
the procedure described by Le Corre for the preparation of 2-ni-
trobenzyltriphenylphosphonium bromide.12
further oxidation step should lead to 12 (Scheme 3). This
assumption was eventually confirmed: when the
benz[b]acridine 11d was kept under H2 atmosphere in the
presence of Pd/C compound 12 was obtained in 65% yield
as the only reaction product (Scheme 4). The presumed
conversion of 13 into 12 is not widely precedented and we
are currently investigating its occurrence in other benzo-
fused pyridines.
6-Phenyl-5,11,11a,12-tetrahydrobenz[b]acridine (5)
HN
To a solution of 2-allyl-1-azidobenzene (1) (0.45 g, 2.8 mmol) in
anhyd toluene (15 mL) Ph3P (0.74 g, 2.8 mmol) was added. The re-
action mixture was stirred at r.t. under N2 for 1 h. Then, a solution
of diphenylketene (0.54 g, 2.8 mmol) in anhyd toluene (2 mL) was
added to the mixture, and the stirring continued for 30 min. The re-
sulting toluene solution was heated at 130 °C in a sealed tube for 16
h. After removing the solvent under reduced pressure the residue
was purified by column chromatography (silica gel; hexane–Et2O,
9:1) to give 5.
N
Ph
12
Yield: 0.34 g, 39%; colourless prisms; mp 158–160°C (Et2O).
IR (Nujol): 3392, 1634, 1610, 1595, 1303, 1165, 761, 725, 703
cm–1.
1H NMR (CDCl3): = 2.73–3.10 (m, 4 H), 3.25–3.45 (m, 1 H), 5.95
(s, 1 H), 6.31 (d, 1 H, J = 7.7 Hz), 6.44 (d, 1 H, J = 7.2 Hz), 6.68 (t,
1 H, J = 7.3 Hz), 6.85–7.07 (m, 5 H), 7.28–7.55 (m, 5 H).
13C NMR (CDCl3): = 33.1, 34.6, 36.1, 109.2 (s), 113.3, 119.5,
122.1 (s), 122.7, 123.5, 126.7, 126.8, 127.5, 128.1, 129.7, 131.4,
137.0 (s), 138.1 (s), 138.2 (s), 139.5 (s).
H2N
11d
12
N
Ph
13
Scheme 3
H2, 10% Pd/C
HN
N
O2N
N
EtOH, 60°C, 14 h (65%)
or
P(OEt)3
o-xylene, reflux, 16 h (30%)
Ph
Ph
11d
12
Scheme 4
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M. Alajarín et al.
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MS (EI): m/z (%) = 309 (M+, 100).
J = 15.7, 6.8 Hz), 6.60 (d, 1 HZ, J = 11.3 Hz), 6.77 (d, 1 HE, J = 15.7
Hz), 6.99–7.33 (m, 14 HZ,E), 7.49 (td, 1 HZ, J = 7.4, 1.4 Hz), 7.59 (d,
1 HZ, J = 7.8 Hz).
13C NMR (CDCl3): = 29.8, 34.6, 118.1, 118.2, 123.4 (s), 124.1 (s),
124.9, 127.0, 127.4, 127.7, 127.9, 128.5, 128.6, 130.0, 130.3, 130.5,
130.6, 130.7, 131.2, 131.6 (s), 132.7, 132.9, 137.3 (s), 138.0 (s).
Anal. Calcd for C23H19N (309.40): C, 89.28; H, 6.19; N, 4.53.
Found: C, 89.23; H, 6.20; N, 4.57.
6-Phenylbenz[b]acridine (6)
To a solution of 5 (50 mg, 0.16 mmol) in anhyd ortho-xylene (4
mL), Pd/C (32 mg) was added. The mixture was stirred at reflux
temperature for 2 h. Then the hot solution was filtered through a
short path of Celite, which afterward was washed with toluene
(3 5 mL). The solvent was removed under reduced pressure and
the residue purified by column chromatography (silica gel; hexane–
Et2O, 7:3) to give 6.
MS (EI): m/z (%) = 287 [(M+ + 2) – N2, 59], 285 (M+ – N2, 64), 204
(100).
Anal. Calcd for C15H12BrN3 (314.18): C, 57.34; H, 3.85; N, 13.37.
Found: C, 57.27; H, 3.80; N, 13.30.
3-(2-Azidophenyl)-1-(4-methylphenyl)propene (9c)
Silica gel; hexane–Et2O, 4:1.
Yield: 48 mg (98%); red needles; mp 209–211°C (Et2O).
IR (Nujol): 1629, 1616, 1588, 1519, 1077, 915, 806, 759, 690 cm–1.
1H NMR (CDCl3): = 7.29–7.45 (m, 3 H), 7.53–7.65 (m, 6 H), 7.90
(t, 2 H, J = 9.1 Hz), 8.00–8.02 (m, 2 H), 8.65 (s, 1 H), 8.96 (s, 1 H).
13C NMR (CDCl3): = 125.0 (s), 125.2, 125.4, 125.9 (s), 126.0,
127.0, 127.1, 127.2, 127.8, 127.9, 128.5, 130.0, 130.6, 131.3 (s),
132.1, 132.6 (s), 136.2, 137.6 (s), 138.2 (s), 143.9 (s), 150.1 (s).
Yield: 0.5 g (52%); ratio Z:E = 10:3.
IR (neat): 2122, 1598, 1584, 1513, 1487, 1450, 1284, 1162, 1148,
1087, 968 cm–1.
1H NMR (CDCl3): = 2.30 (s, 3 HE), 2.34 (s, 3 HZ), 3.46 (d, 2 HE,
J = 6.0 Hz), 3.60 (dd, 2 HZ, J = 7.4, 2.0 Hz), 5.71 (dt, 1 HZ, J = 11.6,
7.4 Hz), 6.23 (dt, 1 HE, J = 17.5, 6.0 Hz), 6.39 (d, 1 HE, J = 17.5
Hz), 6.53 (d, 1 HZ, J = 11.6 Hz), 7.05–7.24 (m, 16 HZ,E).
MS (EI): m/z (%) = 305 (M+, 82), 304 (100).
Anal. Calcd for C23H15N (305.37): C, 90.56; H, 4.95; N, 4.59.
Found: C, 90.31; H, 5.03; N, 4.66.
13C NMR (CDCl3): = 21.0, 21.1, 29.9, 30.0, 118.1, 118.2, 124.4,
126.0, 127.0, 127.5, 127.6, 128.7, 128.9, 129.2, 130.0, 130.2, 130.5,
131.2, 131.8 (s), 132.3 (s), 134.4 (s), 134.6 (s), 136.5 (s), 136.8 (s),
138.0 (s).
1-Aryl-3-(2-azidophenyl)propenes 9; General Procedure
To a solution of the corresponding benzyltriphenylphosphonium
bromide 8 (3.85 mmol) in anhyd CH2Cl2 (25 mL) was added a so-
lution of 2-azidophenylacetaldehyde (7) (0.8 g, 5 mmol) in the same
solvent (5 mL). Then anhyd K2CO3 (0.7 g, 5 mmol) and a catalytic
amount of dibenzo-18-crown-6 were added. The reaction mixture
was stirred at r.t. for 16 h. After separation of the KBr by filtration,
the solvent was removed under reduced pressure and the crude
product was purified by column chromatography to give com-
pounds 9 as colourless oils.
MS (EI): m/z (%) = 222 (27), 221 (M+ – N2, 81), 220 (100).
Anal. Calcd for C16H15N3 (249.31): C, 77.08; H, 6.06; N, 16.85.
Found: 76.90; H, 5.98; N, 16.95.
3-(2-Azidophenyl)-1-(2-nitrophenyl)propene (9d)
Silica gel; hexane–Et2O, 7:3.
Yield: 0.77 g (71%); ratio Z:E = 10:3.
IR (neat): 2122, 1644, 1608, 1582, 1522, 1489, 1450, 1344, 1283,
1150, 1086, 964 cm–1.
1H NMR (CDCl3): = 3.35 (d, 2 HZ, J = 7.5 Hz), 3.54 (d, 2 HE,
J = 6.7 Hz), 5.93 (dt, 1 HZ, J = 11.3, 7.5 Hz), 6.30 (dt, 1 HE,
J = 15.5, 6.7 Hz), 6.86 (d, 1 HZ, J = 11.3 Hz), 7.02–7.63 (m, 15
HZ,E), 7.88 (d, 1 HE, J = 8.0 Hz), 8.04 (d, 1 HZ, J = 8.0 Hz).
13C NMR (CDCl3): = 29.9, 34.7, 118.1, 118.3, 124.5, 124.6,
124.9, 126.5, 126.9, 127.7, 127.8, 128.0, 128.6, 129.9, 130.7, 131.1,
131.8, 132.6 (s), 132.8, 132.9, 133.0 (s), 133.7, 148.3 (s).
3-(2-Azidophenyl)-1-(2-bromophenyl)propene (9a)
Silica gel; hexane–Et2O, 9:1.
Yield: 0.85 g (74%); ratio Z:E = 2:1.
IR (neat): 2122, 1646, 1581, 1487, 1465, 1449, 1436, 1286, 1046,
966 cm–1.
1H NMR (CDCl3): = 3.44 (d, 2 HZ, J = 7.4 Hz), 3.52 (d, 2 HE,
J = 6.8 Hz), 5.87 (dt, 1 HZ, J = 11.2, 7.4 Hz), 6.22 (dt, 1 HE,
J = 15.9, 6.8 Hz), 6.60 (d, 1 HZ, J = 11.2 Hz), 6.77 (d, 1 HE, J = 15.9
Hz), 7.00–7.32 (m, 14 HZ,E), 7.48 (t, 1 HZ, J = 7.8 Hz), 7.59 (d, 1 HZ,
J = 7.8 Hz).
13C NMR (CDCl3): = 29.8, 34.6, 118.1, 118.2, 123.4 (s), 124.1 (s),
124.9, 127.0, 127.4, 127.7, 127.9, 128.5, 128.6, 130.0, 130.1, 130.2,
130.5, 130.6, 130.7, 131.1, 131.6 (s), 132.6, 132.9, 137.3 (s), 138.0
(s).
MS (EI): m/z (%) = 252 (M+ – N2, 30), 117 (100).
Anal. Calcd for C15H12N4O2 (280.28): C, 64.28; H, 4.32; N, 19.99.
Found: C, 64.13; H, 4.41; N, 20.08.
3-(2-Azidophenyl)-1-(4-nitrophenyl)propene (9e)
Silica gel; hexane–Et2O, 7:3.
Yield: 0.86 g (80%).
MS (EI): m/z (%) = 287 [(M+ + 2) – N2, 90], 285 (M+ – N2, 91), 204
IR (neat): 2122, 1645, 1597, 1512, 1489, 1450, 1339, 1281, 1180,
1111, 1091 cm–1.
1H NMR (CDCl3): = 3.58 (dd, 2 H, J = 7.4, 1.3 Hz), 5.97 (dt, 1 H,
J = 11.6, 7.4 Hz), 6.60 (d, 1 H, J = 11.6 Hz), 7.05–7.35 (m, 4 H),
7.44 (d, 2 H, J = 8.6 Hz), 8.20 (d, 2 H, J = 8.6 Hz).
(100).
Anal. Calcd for C15H12BrN3 (314.18): C, 57.34; H, 3.85; N, 13.37.
Found: C, 57.19; H, 3.89; N, 13.25.
3-(2-Azidophenyl)-1-(4-bromophenyl)propene (9b)
Silica gel; hexane–Et2O, 9:1.
13C NMR (CDCl3): = 30.2, 34.7, 118.1, 118.3, 123.6, 123.9,
125.0, 126.6, 128.0, 128.1, 128.4, 129.3, 129.4, 129.9, 130.7, 131.0
(s), 133.5, 138.1 (s), 143.9 (s).
Yield: 0.66 g (55%); ratio Z:E = 2:1.
IR (neat): 2120, 1644, 1582, 1560, 1486, 1470, 1451, 1283, 1147,
1025, 970 cm–1.
MS (EI): m/z (%) = 252 (M+ – N2, 99), 204 (100).
1H NMR (CDCl3): = 3.44 (d, 2 HZ, J = 7.4 Hz), 3.52 (d, 2 HE,
J = 6.8 Hz), 5.88 (dt, 1 HZ, J = 11.3, 7.4 Hz), 6.23 (dt, 1 HE,
Anal. Calcd for C15H12N4O2 (280.28): C, 64.28; H, 4.32; N, 19.99.
Found: C, 64.39; H, 4.24; N, 19.93.
Synthesis 2002, No. 16, 2393–2398 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Intramolecular [4 + 2] Cycloaddition Reactions of Ketenimines: A New Synthesis of Benz[b]acridines
2397
3-(2-Azidophenyl)-1-(4-methoxyphenyl)propene (9f)
MS (EI): m/z (%) = 461 (M+ + 2, 31), 459 (M+, 35), 189 (100).
Silica gel; hexane–Et2O, 4:1.
Anal. Calcd for C29H18BrN (460.36): C, 75.66; H, 3.94; N, 3.04.
Found: C, 75.56; H, 3.83; N, 3.11.
Yield: 0.36 g (35%); ratio Z:E = 3:1.
IR (neat): 2125, 1646, 1607, 1583, 1509, 1490, 1465, 1453, 1288,
1253, 1177, 1087, 1038, 967 cm–1.
6-Phenyl-11-(4-methylphenyl)benz[b]acridine (11c)
Silica gel; hexane–EtOAc, 9:1.
1H NMR (CDCl3): = 3.46 (d, 2 HE, J = 6.6 Hz), 3.59 (dd, 2 HZ,
J = 7.2, 1.8 Hz), 3.77 (s, 3 HE), 3.80 (s, 3 HZ), 5.67 (dt, 1 HZ,
J = 11.4, 7.2 Hz), 6.15 (dt, 1 HE, J = 15.9, 6.6 Hz), 6.35 (d, 1 HE,
J = 15.9 Hz), 6.51 (d, 1 HZ, J = 11.4 Hz), 6.81 (d, 2 HE, J = 8.7 Hz),
6.87 (d, 2 HZ, J = 7.8 Hz), 7.04–7.28 (m, 12 HZ,E).
13C NMR (CDCl3): = 29.8, 30.0, 55.3, 113.8, 114.0, 118.1, 124.9,
125.9, 127.3, 127.6, 127.7, 128.2, 129.9, 130.0, 130.6, 130.7, 132.7
(s), 138.1 (s), 158.6 (s).
Yield: 0.2 g (50%); red prisms; mp 227–228 °C (Et2O).
IR (Nujol): 1626, 1599, 1578, 1515, 1504, 1118, 1125, 1010, 965,
949, 842, 760, 749, 737, 698 cm–1.
1H NMR (CDCl3): = 2.55 (s, 3 H), 7.26–7.32 (m, 3 H), 7.39–7.45
(m, 4 H), 7.53–7.65 (m, 6 H), 7.73–7.78 (m, 2 H), 7.90–7.93 (m, 1
H), 8.00 (d, 1 H, J = 9.0 Hz), 8.69 (s, 1 H).
13C NMR (CDCl3): = 21.5, 124.6 (s), 125.1, 125.2, 125.8, 127.1,
127.2, 127.4, 127.8, 128.4, 129.4, 129.6 (s), 130.1, 130.5, 131.5,
132.3, 132.5 (s), 135.2 (s), 135.6, 137.5 (s), 137.7 (s), 138.0 (s),
138.8 (s), 143.6 (s), 149.8 (s).
MS (EI): m/z (%) = 237 (M+ – N2, 99), 236 (100).
Anal. Calcd for C16H15N3O (265.31): C, 72.43; H, 5.70; N, 15.84.
Found: C, 72.55; H, 5.76; N, 15.72.
MS (EI): m/z (%) = 395 (M+, 100).
11-Aryl-6-phenylbenz[b]acridines 11; General Procedure
To a solution of the corresponding 1-aryl-3-(2-azidophenyl)pro-
pene 9 (1 mmol) in anhyd toluene (20 mL), Ph3P (0.26 g, 1 mmol)
was added. The reaction mixture was stirred at r.t. under N2 for 1 h.
Then a solution of diphenylketene (0.19 g, 1 mmol) in anhyd tolu-
ene (2 mL) was added, and the mixture stirred at r.t. for 30 min. The
resulting toluene solution was heated at 130 °C in a sealed tube for
16 h. The toluene was removed under reduced pressure, the residue
dissolved in anhyd ortho-xylene (4 mL) and after addition of Pd/C
(0.2 g) the mixture was stirred at reflux temperature for 5 h. Then
the hot solution was filtered through a short path of Celite, which af-
terward was washed with toluene (3 5 mL). From the combined
solution, the solvent was removed under reduced pressure and the
residue purified by column chromatography.
Anal. Calcd for C30H21N (395.49): C, 91.11; H, 5.35; N, 3.54.
Found: C, 91.02; H, 5.25; N, 3.48.
6-Phenyl-11-(2-nitrophenyl)benz[b]acridine (11d)
Silica gel; hexane–Et2O, 4:1.
Yield: 85 mg (20%); orange prisms; mp 214 °C (Et2O).
IR (Nujol): 1627, 1607, 1523, 1349, 1161, 1070, 1037, 962, 851,
767, 741, 705, 663 cm–1.
1H NMR (CDCl3): = 7.24–7.46 (m, 4 H), 7.56–7.95 (m, 11 H),
8.03 (d, 1 H, J = 8.8 Hz), 8.34 (dd, 1 H, J = 7.6, 1.4 Hz), 8.42 (s, 1
H).
13C NMR (CDCl3): = 124.0 (s), 124.9, 125.6, 125.7, 125.8, 125.9
(s), 126.2, 127.3, 127.7 (s), 127.8, 127.9, 128.2, 129.2 (s), 129.7,
130.3, 130.5, 132.1, 132.3 (s), 132.4, 133.4, 134.3, 138.4 (s), 138.7
(s), 143.4 (s), 149.8 (s), 150.4 (s).
11-(2-Bromophenyl)-6-phenylbenz[b]acridine (11a)
Silica gel; hexane–Et2O, 4:1.
MS (EI): m/z (%) = 426 (M+, 72), 378 (100).
Yield: 0.19 g (40%); red prisms; mp 200–202 °C (Et2O).
Anal. Calcd for C29H18N2O2 (426.47): C, 81.67; H, 4.25; N, 6.57.
Found: C, 81.68; H, 4.13; N, 6.51.
IR (Nujol): 1632, 1600, 1574, 1525, 1131, 1073, 1031, 960, 904,
853, 811, 769, 746, 702 cm–1.
1H NMR (CDCl3): = 7.30–7.36 (m, 3 H), 7.45–7.50 (m, 2 H),
7.52–7.65 (m, 7 H), 7.68–7.70 (m, 1 H), 7.78 (d, 1 H, J = 8.4 Hz),
7.91 (d, 1 H, J = 8.4 Hz), 7.95 (dd, 1 H, J = 6.6, 3.0 Hz), 8.02 (d, 1
H, J = 8.7 Hz), 8.47 (s, 1 H).
6-Phenyl-11-(4-nitrophenyl)benz[b]acridine (11e)
Silica gel; hexane–Et2O, 9:1.
Yield: 0.14 g (33%) red prisms; mp 335–337 °C (Et2O).
13C NMR (CDCl3): = 123.9 (s), 125.5, 125.8, 125.9, 126.0 (s),
126.4, 127.2, 127.6, 127.7, 127.8, 128.4, 129.4 (s), 129.9, 130.1,
130.6, 132.2, 132.4, 132.5 (s), 133.3, 134.6, 136.2 (s), 138.5 (s),
138.6 (s), 139.2 (s), 143.7 (s), 149.9 (s).
IR (Nujol): 1591, 1513, 1346, 1108, 1037, 968, 918, 853, 825, 764,
742, 699 cm–1.
1H NMR (CDCl3 + TFA): = 7.56–7.85 (m, 12 H), 8.14–8.20 (m,
2 H), 8.32 (d, 1 H, J = 9.2 Hz), 8.64 (d, 2 H, J = 8.7 Hz), 9.41 (s, 1
H).
MS (EI): m/z (%) = 461 (M+ + 2, 34), 459 (M+, 37), 378 (100).
13C NMR (CDCl3 + TFA): = 119.5, 122.9 (s), 124.6, 125.3 (s),
127.0, 127.3, 128.2, 129.0, 130.2 (s), 130.3, 130.5, 130.8 (s), 131.0,
131.2 (s), 131.4, 132.0, 132.3 (s), 132.7, 137.5 (s), 139.4 (s), 141.0,
141.9 (s), 142.0 (s), 148.9 (s), 150.1.
Anal. Calcd for C29H18BrN (460.36): C, 75.66; H, 3.94; N, 3.04.
Found: C, 75.70; H, 3.88; N, 2.98.
11-(4-Bromophenyl)-6-phenylbenz[b]acridine (11b)
Silica gel; hexane–Et2O, 4:1.
MS (EI): m/z (%) = 426 (M+, 75), 189 (100).
Yield: 0.13 g (27%); red prisms; mp 205 °C (Et2O).
Anal. Calcd for C29H18N2O2 (426.47): C, 81.67; H, 4.25; N, 6.57.
Found: C, 81.53; H, 4.34; N, 6.65.
IR (Nujol): 1624, 1595, 1576, 1522, 1126, 1072, 1025, 911, 899,
850, 810, 769, 742, 701 cm–1.
6-Phenyl-11-(4-methoxyphenyl)benz[b]acridine (11f)
Silica gel; hexane–Et2O, 4:1.
1H NMR (CDCl3 + TFA): = 7.47 (d, 2 H, J = 8.4 Hz), 7.54–7.80
(m, 9 H), 7.89–7.93 (m, 3 H), 8.17 (d, 2 H, J = 7.4 Hz), 8.27 (d, 1
H, J = 9.2 Hz), 9.54 (s, 1 H).
Yield: 0.15 g (36%); red prisms; mp 155–157 °C (Et2O).
13C NMR (CDCl3 + TFA): = 120.6, 123.3 (s), 124.4 (s), 125.0 (s),
126.9, 127.7, 127.8, 128.2, 129.3 (s), 129.5 (s), 130.1, 130.3, 130.7,
130.8 (s), 131.5, 132.5 (s), 132.7, 132.9, 133.8 (s), 137.5 (s), 140.3,
141.0 (s), 142.2 (s), 150.3.
IR (Nujol): 1606, 1574, 1513, 1284, 1247, 1185, 1175, 1104, 913,
839, 818, 766, 745, 702 cm–1.
1H NMR (CDCl3): = 4.00 (s, 3 H), 7.20 (d, 2 H, J = 8.6 Hz), 7.30–
7.37 (m, 3 H), 7.47 (d, 2 H, J = 8.6 Hz), 7.55–7.67 (m, 6 H), 7.78–
Synthesis 2002, No. 16, 2393–2398 ISSN 0039-7881 © Thieme Stuttgart · New York

2398
M. Alajarín et al.
PAPER
7.81 (m, 2 H), 7.90–7.94 (m, 1 H), 8.02 (d, 1 H, J = 8.8 Hz), 8.72 (s,
1 H).
Acknowledgement
This work was supported by the MCYT and FEDER (Project
BQU2001-0010), and Fundación Séneca-CARM (Project PI-1/
00749/FS/01). One of us (M.-M. O.) thanks the Fundación Séneca-
CARM for a fellowship.
13C NMR (CDCl3): = 55.5, 114.2, 124.8 (s), 125.2, 125.3, 125.8,
127.1, 127.2, 127.4, 127.9, 128.5, 129.9 (s), 130.1, 130.4 (s), 130.5,
132.3, 132.5 (s), 132.7, 135.6, 137.5 (s), 137.8 (s), 138.8 (s), 143.7
(s), 149.8 (s), 160.5 (s).
MS (EI): m/z (%) = 411 (M+, 100).
References
Anal. Calcd for C30H21NO (411.49): C, 87.56; H, 5.14; N, 3.40.
Found: 87.58; H, 5.05; N, 3.31.
(1) (a) Barker, M. W.; McHenry, W. E. In The Chemistry of
Ketenes, Allenes and Related Compounds, Part. 2; Patai, S.,
Ed.; Wiley: Chichester, 1980, 701. (b) Alajarín, M.; Vidal,
A.; Tovar, F. Targets Heterocycl. Syst. 2000, 4, 293; and
references cited therein..
9-Phenyl-15H-benzo[i]quino[4,3,2-kl]acridine (12)
Yield: 0.14 g (36%); colourless prisms; mp 245 °C (EtOAc–n-hex-
ane).
(2) (a) Molina, P.; Alajarín, M.; Vidal, A. Tetrahedron Lett.
1991, 32, 5379. (b) Molina, P.; Alajarín, M.; Vidal, A. J.
Org. Chem. 1992, 57, 6703.
(3) Alajarín, M.; Vidal, A.; Tovar, F.; Conesa, C. Tetrahedron
Lett. 1999, 40, 6127.
IR (Nujol): 3402, 1617, 1607, 1591, 1567, 1553, 1503, 1235, 1157,
851, 766, 745, 707, 676 cm–1.
1H NMR (CDCl3): = 6.68 (d, 1 H, J = 8.1 Hz), 6.99 (s, 1 H), 7.06–
7.11 (m, 1 H), 7.30 (ddd, 1 H, J = 8.2, 7.0, 1.4 Hz), 7.46–7.49 (m, 5
H), 7.53–7.61 (m, 2 H), 7.65–7.74 (m, 3 H), 8.20 (dd, 1 H, J = 8.2,
1.0 Hz), 8.80 (d, 1 H, J = 7.2 Hz), 8.86 (d, 1 H, J = 8.4 Hz), 8.97–
9.00 (m, 1 H).
13C NMR (CDCl3): = 114.8, 116.3 (s), 120.0 (s), 121.2, 123.0,
123.5 (s), 124.0 (s), 124.8, 125.4, 126.0, 127.7, 128.0, 128.5, 128.6,
128.9, 129.5, 130.3, 131.5, 132.7 (s), 133.0 (s), 135.3 (s), 135.6 (s),
139.3 (s), 147.7 (s), 149.7 (s).
(4) Alajarín, M.; Vidal, A.; Tovar, F. Tetrahedron Lett. 2000,
41, 7029.
(5) General syntheses of benz[b]acridines have been scarcely
reported and usually yield oxidized derivatives. For
examples, see: (a) Narasimhan, N. S.; Ranade, A. C. Indian
J. Chem. 1969, 7, 538. (b) Roushdi, I. M.; Mikhail, A. A.;
Chaaban, I. Pharmazie 1976, 31, 406. (c) Joos, K.; Pardo,
M.; Schäfer, W. J. Chem. Res., Synop. 1978, 406.
(d) Hamdan, A. J.; Moore, H. W. J. Org. Chem. 1985, 50,
3427. (e) Chuang, C.-P.; Wu, Y.-L.; Jiang, M.-C.
Tetrahedron 1999, 55, 11229. (f) Prato, M.; Scorrano, G.;
Stiranello, M.; Tecilla, P.; Lucchini, V. Gazz. Chim. Ital.
1987, 117, 325. (g) Alvarez, M.; Ajana, W.; López-
Calahorra, F.; Joule, J. A. J. Chem. Soc., Perkin Trans. 1
1994, 917.
(6) (a) Staudinger, H.; Meyer, J. Helv. Chim. Acta 1919, 2, 635.
(b) Gololobov, Y. G.; Kasukhin, L. F. Tetrahedron 1992, 48,
1353. (c) Gololobov, Y. G.; Zhmurova, I. N.; Kasukhin, L.
F. Tetrahedron 1981, 37, 437.
(7) Smith, P. A. S.; Chou, S. P. J. Org. Chem. 1981, 46, 3970.
(8) Compound 2 31P NMR (121.4 MHz, CDCl3): = 1.29.
(9) The heating of the toluene solutions of the ketenimines 10 at
130 °C in a sealed tube gave mixtures of 5,11,11a,12-
tetrahydro, 5,12-dihydro and the fully aromatic 11-aryl-6-
phenylbenz[b]acridines, and the same results were obtained
when this thermal treatment was carried out in the presence
of Pd/C.
MS (EI): m/z (%) = 394 (M+, 100).
Anal. Calcd for C29H18N2 (394.47): C, 88.30; H, 4.60; N, 7.10.
Found: C, 88.11; H, 4.70; N, 7.18.
9-Phenyl-15H-benzo[i]quino[4,3,2-kl]acridine (12)
Method A
To a solution of 11d (0.1 g, 0.23 mmol) in EtOH (25 mL) was added
Pd/C (10 mg) and the mixture stirred at 60 °C under H2 atm for 14
h. Then the solution was filtered through a short path of Celite, the
solvent removed under reduced pressure, and the crude material pu-
rified by column chromatography (silica gel; hexane–Et2O, 7:3) to
give 12.
Yield: 60 mg (65%).
Method B
A solution of 11d (64 mg, 0.15 mmol) in a mixture of triethylphos-
phite (1 mL) and ortho-xylene (4.5 mL) was heated at reflux tem-
perature for 16 h. The solvent was removed under reduced pressure
and the crude material purified by column chromatography (silica
gel, hexane–Et2O, 7:3) to give 12.
(10) (a) Alkhader, M. A.; Smalley, R. K.; Mohajerani, B.
Synthesis 1980, 381. (b) Bassoli, A.; Maddinelli, G.;
Rindone, B.; Tollari, S.; Chioccara, F. J. Chem. Soc., Chem.
Commun. 1987, 150.
Yield: 18 mg (30%).
(11) Taylor, E. C.; McKillop, A.; Hawks, G. H. Org. Synth. 1973,
52, 36.
(12) Le Corre, M.; Hercouet, A.; Le Stanc, Y.; Le Baron, H.
Tetrahedron 1985, 41, 5313.
Synthesis 2002, No. 16, 2393–2398 ISSN 0039-7881 © Thieme Stuttgart · New York