Synthesis of a naphtho-pyrido-annulated iodonium salt and pd-catalyzed transformation to 7 H-Naphtho[1,8-bc ][1,5]naphthyridine

Article abstract of DOI:10.1055/s-0033-1338530

Nitropyridylnaphthalene is the central intermediate for the synthesis of naphthonaphthyridine and benzo-δ-carboline. Whereas the Cadogan reaction gives the carboline, transformation of the nitro group to iodo followed by oxidation and cyclization results in an iodonium salt. A twofold Pd-catalyzed amination leads to the naphthyridine. Georg Thieme Verlag Stuttgart, New York.

Full text of DOI:10.1055/s-0033-1338530

PAPER
▌3173
paper
Synthesis of a Naphtho-pyrido-Annulated Iodonium Salt and Pd-Catalyzed
Transformation to 7H-Naphtho[1,8-bc][1,5]naphthyridine
Naphthonaphthyridine
Julien Letessier, Mario Geffe, Dieter Schollmeyer, Heiner Detert*
Institute for Organic Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10–14, 55099 Mainz, Germany
Fax +49(6131)3925338; E-mail: detert@uni-mainz.de
Received: 23.06.2013; Accepted after revision: 22.08.2013
Dedicated to Heinz Kolshorn on the occasion of his 70th birthday
ortho position of the remote aryl moiety results in the for-
Abstract: Nitropyridylnaphthalene is the central intermediate for
mation of the bisannulated iodolium salts. In the presence
the synthesis of naphthonaphthyridine and benzo-δ-carboline.
of a Pd/phosphine catalytic system, these salts are able to
arylate primary amines. An initial ring opening to a 2-ami-
Whereas the Cadogan reaction gives the carboline, transformation
of the nitro group to iodo followed by oxidation and cyclization re-
sults in an iodonium salt. A twofold Pd-catalyzed amination leads no-2′-iodobiaryl is followed by intramolecular ring clo-
to the naphthyridine.
sure delivering the anticipated carbazole or carboline
framework. Therefore, o-nitrobiaryls are the central inter-
mediates for the iodolium and the Cadogan route to
(aza)carbazoles. Furthermore, both methodologies have
in common the construction of the pyrrole core. Neverthe-
less these are complimentary methods. In the Cadogan re-
action, the pyrrole is formed in a reductive cyclization
with trivalent phosphorus reagents, whereas the first key
step of the iodolium route is an oxidative cyclization of an
o-iodobiaryl to give a hypervalent iodolium salt. Second-
ly, the twofold palladium-catalyzed amination of the iod-
olium salts leads to (aza)carbazoles substituted on the
pyrrole nitrogen whereas only unsubstituted derivatives
are obtained by the classical routes. With almost perfect
selectivity, pyrroles are formed in the Cadogan reaction.9
Most known cyclic iodonium salts are also five-mem-
bered rings,12 only a limited number of larger cyclic iodo-
nium salts have been reported.13 Whereas the iodolium
salts are suitable substrates for twofold arylation, no re-
ports of analogous conversions of six-membered iodoni-
um salts appeared in the literature. Herein, we describe the
preferential formation of a six-membered iodonium salt
and the first successful transformation of the latter to a
pyridine ring, resulting in N-substituted 7H-naphtho[1,8-
bc][1,5]naphthyridine, a hitherto unknown tetracyclic
base.
Key words: amination, fused-ring systems, heterocycles, iodine,
palladium, catalysis
Carbazole and carbolines are important as scaffolds for a
large number of biologically active alkaloids and synthet-
ic derivatives.1 Several methods for the synthesis of these
units are known. The Graebe–Ullmann, the Borsche syn-
thesis, and the Cadogan cyclization are probably the most
prominent routes.2 Nevertheless, all routes have limita-
tions and the need for specific substitution patterns
prompted us to search for new routes to these tricyclic sys-
tems. In addition to the successful approaches via [2+2+2]
cycloaddition,3 cyclizations of nitrobiaryls and of indo-
loaminonitriles,4 we have started to apply hypervalent io-
dolium salts as intermediates.5 Diaryliodonium salts are
known to be efficient arylating agents for a variety of nu-
cleophiles such as arenes, alkynes, or carbonyl com-
pounds.6 The copper- and palladium-catalyzed arylation
of phenols or anilines using diaryliodonium salts 7 trans-
fers one aryl ring to the heteroatom of the substrate, which
results in the formation of iodoarenes as byproducts. The
latter are typical substrates in palladium-catalyzed N-ary-
lations, this methodology has been extensively developed
by Buchwald and Hartwig.8
Recently, we have applied the Cadogan reaction9 to the
synthesis of indolocarbazoles and related extended π-sys-
tems.10 The palladium-catalyzed cross-coupling reaction
between boronic acids and o-nitrohaloarenes allows a fast
access to the required starting materials for the reductive
cyclization. Furthermore, these o-nitrobiaryls11 also ap-
peared to be valuable starting materials for the iodolium
route, our lately developed new route for the synthesis of
(aza)carbazoles.6i,12 This approach requires the transfor-
mation of the o-nitrobiaryls to o-iodobiaryls. Oxidation of
the iodoarenes leads to the iodoso compounds and an in-
tramolecular attack of the protonated iodoso group on the
The formation of the o-iodobiaryl unit was performed by
the Suzuki reaction of 2-chloro-3-nitropyridine (1) and
naphthalen-1-ylboronic acid (2) to give nitropyridyl-
naphthalene 3 in excellent yield (Scheme 1). Catalytic re-
duction of the nitro group to 4 followed by diazotization
and in situ Sandmeyer reaction yields 5 (49%). Among a
variety of mixtures of peroxo compounds and strong acids
with non-nucleophilic anions, the combination of 3-chlo-
roperoxybenzoic acid and triflic acid appeared to be the
best reagent for the remote functionalization.5 Triflic acid
protects the pyridine nitrogen from oxidation and effi-
ciently protonates the iodoso group, thus initiating the in-
tramolecular electrophilic substitution on the naphthalene
unit. An 8:1 mixture of two hypervalent iodonium salts
6a/6b was formed that could not be separated by crystal-
SYNTHESIS 2013, 45, 3173–3178
Advanced online publication: 18.09.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
1
DOI: 10.1055/s-0033-1338530; Art ID: SS-2013-Z0431-OP
© Georg Thieme Verlag Stuttgart · New York
lization. In the H NMR spectrum, the major compound

3174
J. Letessier et al.
PAPER
B(OH)2
N
N
Pd/C, H2
THF, 98%
NH2
2
NO2
NO2
Cl
Pd/C, Ph3P
DME, Na2CO3
80°C, 98%
N
4
1
3
MCPBA
O
p-TsOH, NaNO2
KI, MeCN, 0 °C
49%
TfOH
CH2Cl2
0 °
N
N
I
I
5
5a
TfO
I
TfOH
CH2Cl2
0 °C, 65%
N
N
I
TfO
+
6a
8/1
6b
Scheme 1 Synthesis of naphtho-pyrido-iodonium salt 6a
6a showed three AMX spin systems, giving evidence for posed of four six-membered rings. The unsubstituted 7H-
a cyclization from the iodine into the β-position of the naphtho[1,8-bc][1,5]naphthyridine (8) was obtained in
naphthalene core. According to extensive NMR investiga- nearly quantitative yield via base-induced debenzylation
tions, 6a contains a six-membered cyclic iodonium ring of 8.
with a peri-annulated naphthalene system. This is proba-
bly the first example of the preferential formation of a six-
In an additional experiment, we could prove that the peri-
functionalization in the formation of 6a is a unique feature
membered ring iodonium salt if both five- and six-mem-
of the iodolium salt route. Microwave-assisted Cadogan
bered rings were possible. The second compound is prob-
reaction of nitro-biaryl 3 results in the exclusive formation
of benzocarboline 10 (Scheme 3).
ably the isomeric five-membered-ring iodonium salt 6b.
Using the successful protocol for the transformation of an-
nulated iodolium salts to pyrroles12 we succeeded in the
twofold Buchwald–Hartwig arylation of benzylamine
with 6a to give compound 7 in 53% yield accompanied by
the formation of small amounts of benzo-δ-carboline 9
(Scheme 2). According to all spectroscopic data including
HMBC and HSQC experiments, the new base 7 is com-
(EtO)3P
MW (300 W)
210 °C, 65%
N
N
NO2
NH
3
10
Scheme 3 Synthesis of benzo-δ-carboline 10
TfO
TfO
Pd2(dba)3 /Xantphos
Cs2CO3, toluene
BnNH2
N
N
I
I
+
The absorption and emission spectra of the isomeric het-
erocycles 8 and 10 are significantly different (see the Sup-
porting Information).
100 °C, 60% (7 + 9)
8/1
+
6a
6b
The UV-vis absorption spectrum of 8 in cyclohexane is
highly structured, three main absorption bands
(λmax = 206, 259, 331 nm) appear in the UV and a broad
one in the visible spectrum (λmax = 423 nm). The vibra-
tional fine structure is blurred in more polar solvents and
a weak positive solvatochromism has to be noted. In cy-
clohexane, 8 fluoresces intensively with λFmax = 459 nm
(2nd max: λF = 488 nm). According to the rigid molecular
structure, the Stokes shift is very small (386 cm–1). In-
creasing solvent polarity shifts the emission maximum to
7
N
N
Bn
N
KOt-Bu
DMSO
air, 98%
N
HN
Bn
N
9
7
8
7/1
Scheme 2 Palladium-catalyzed arylamination of iodonium salts
6a,b to give naphtho-naphthyridine 7 and benzo-δ-carboline 9
Synthesis 2013, 45, 3173–3178
© Georg Thieme Verlag Stuttgart · New York

PAPER
Naphthonaphthyridine
3175
λFmax = 487 nm in dichloromethane and to λFmax = 512 nm
in ethanol. Upon addition of trifluoroacetic acid to solu-
tions of 8 in dichloromethane, a protonated species is
formed in 10–4 M trifluoroacetic acid, protonation is com-
plete in 10–3 M trifluoroacetic acid and protonated 8 ab-
sorbs with λmax = 525 nm. This red shift corresponds to a
pronounced electronic donor-acceptor structure, resulting
from protonation of the lateral pyridine. AM1-INDO/S
calculations substantiate this interpretation. Nevertheless,
though protonation of 8 in its ground state shifts the elec-
tronic transition to lower energies, protonation of its excit-
ed state results in quenching of the blue emission
(λFmax = 487 nm) and a new, violet emission (λFmax = 414
nm in 10–2 M TFA) appears. This intense fluorescence is
quenched in the presence of high concentrations of triflu-
oroacetic acid.
The isomeric carboline 10 absorbs only in the UV:
λ
max = 250 nm, and a band at lower energies with two in-
Figure 1 Molecular structure of benzyl-naphthonaphthyridine 7
tense maxima: λ = 319, 333 nm. The light emitted by this
species in cyclohexane has a λFmax = 394 nm, a negative
solvatochromism of the emission shifts the maximum to
381 nm in ethanol. An addition of trifluoroacetic acid
(10–4 M) to the solution of 10 in dichloromethane causes
a small shift of the absorption maximum to λmax = 350 nm
with a shoulder centered at λ = 390 nm. Higher concentra-
tions of trifluoroacetic acid have only a weak effect on the
absorption. Quenching of the fluorescence starts at 10–5 M
trifluoroacetic acid, only a very weak emission with
λFmax = 452 nm remains in solutions with higher concen-
trations of trifluoroacetic acid.
er than in the β-position. With a successive protonation of
pyridine and iodoso group, the relative charge density
peri/β increases to 180:1, therefore directing the electro-
philic attack into the peri-position. Under the conditions
of a Buchwald–Hartwig arylation, iodonium salt 6a reacts
with benzylamine. In the first step, ring opening to an
iodo-amino derivative occurs and the pyridine ring is
closed in an intramolecular palladium-catalyzed arylation
to yield 53% of 7. Up to now, the iodolium and the
Cadogan route have been regarded as alternative methods
for the cyclization of nitrobiaryls to (aza)carbazoles. In
the special case of a possible peri-functionalization,15 the
iodolium route allows access to six-membered cyclic io-
donium salts. Furthermore, we could show that these are
suitable substrates for the palladium-catalyzed formation
of pyridine rings, opening a new route to annulated naph-
thyridines.16 For comparison purposes, we subjected 3 to
the conditions of the Cadogan reaction.10 The yield of the
anticipated benzocarboline 10 was 65%, spectroscopy did
not give any evidence for the formation of the isomeric
compound 8.
X-ray analysis of 7-benzylnaphthonaphthyridine 7 gave
final proof of the molecular structure (Figure 1). The
monoclinic crystals are formed from centrosymmetric
pairs of 7, connected via π-stacking with a distance of
3.491(1) Å between the centroids of the central pyridine
ring of one molecule and the lateral pyridine ring of the
other. With an angle of 80.1(1)°, the plane of the benzyl
ring is close to orthogonal to the plane of the completely
flat naphthonaphthyridine. The C–N8 bond lengths of
1.330 Å and 1.340 Å in the lateral ring correspond to a
normal pyridine system whereas the C–N1 bond lengths
in the central ring are significantly longer (1.391, 1.397
Å). Similarly, the bond C7A–C7B (1.465 Å), connecting
the pyridine and naphthalene units, is much longer than all
other bonds in the tetracyclic framework.
All reactions were carried out under dry argon or N2 unless other-
wise indicated. Commercially available reagents were used without
further purification unless otherwise indicated; solvents and gases
were dried by standard procedures. Yields refer to chromatograph-
The Cadogan reaction of o-nitrobiaryl units with trivalent ically and spectroscopically pure compounds unless otherwise stat-
1
ed. H and 13C NMR spectra: Bruker AC 300 (300 MHz), Bruker
phosphorus reagents belongs to the most important syn-
AV 400 (400 MHz), and Bruker ARX 400 (400 MHz); CDCl3 or
DMSO-d6. The H and C signals were assigned on the basis of
DEPT, COSY 45, HMQC, and HMBC experiments; atom number-
ing for 6–10 is shown in Figure 2. Melting points: Büchi HWS SG
thetic routes to carbazoles and has recently also been ap-
plied to the synthesis of carboline derivatives.14 This
reductive cyclization is characterized by the exclusive for-
mation of pyrrole rings,9 probably via electrocyclization
200. IR spectra: Jasco 4100 FT-IR (ATR). FD-MS spectra: Mat 95
(Finnigan); HRMS (ESI): Q-TOF-ULTIMA 3 with Lock Spray de-
vice (Waters-Micromass), NaICsI as reference. UV-vis spectra:
Perkin-Elmer Lambda 16. Fluorescence spectra: Perkin-Elmer LS
50B. Elemental analyses: Vario EL. Semiempirical calculations of
structures and charge densities were performed on the AM1 level
using the MOPAC package. Column chromatography on silica gel;
PE = petroleum ether.
of an intermediary 1-azapentadiene anion. In our ap-
proach, the functionalization of the remote aromatic ring
is performed via an electrophilic attack of the protonated
o′-iodoso group. The regioselectivity is controlled by the
charge density in the sterically accessible positions. AM1-
calculations predict a charge density on the peri-position
of the naphthalene system in 5b (iodoso) about 33% high-
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 3173–3178

3176
J. Letessier et al.
PAPER
2-(Naphthalen-1-yl)-3-nitropyridine (3)
HRMS: m/z [M + H]+ calcd for C15H11IN: 331.9936; found:
331.9946.
A mixture of 1 (200 mg, 1.26 mmol), 2 (270 mg, 1.58 mmol), Ph3P
(34 mg, 0.13 mmol), DME (5 mL), 2 M aq Na2CO3 (2.5 mL), and
10% Pd/C (60 mg, 0.06 mmol) was stirred for 16 h at 80 °C, fol-
lowed by filtration through Celite and washing the filter cake with
EtOAc (4 × 7 mL). The combined filtrates were washed with 10%
NaOH and brine, dried (MgSO4), and concentrated, and the residue
was purified by chromatography (PE–EtOAc, 5:1) to give 3 (312
mg, 98%) as a yellow oil. Previously reported analytical data14 for
3 are incorrect.
9
9
8
8
10
10
7a
7a
N
N
11a
11b
11a
X
NH
6a
1
11b
5
6a
11c
11c
2
6
1
2
6
5
3
4a
3a
4
4
3
IR (neat, ATR): 1590, 1560, 1524, 1392, 1348, 1232, 1082, 862,
803, 777, 726, 661 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.98 (dd, J = 4.7, 1.6 Hz, 1 H, 6-
Figure 2 Atom numbering in 6–10
CH), 8.37 (dd, J = 8.2, 1.4 Hz, 1 H), 7.95 (m, 2 H), 7.45–7.60 (m, 6
H).
13C NMR (75 MHz, CDC l3): δ = 153.4 (s), 152.6 (d), 147.2 (s),
134.4 (s), 133.6 (s), 132.3 (d), 130.9 (s), 129.7 (d), 128.6 (d), 126.9
(d), 126.4 (d), 126.2 (d), 125.2 (d), 124.2 (d), 123.0 (d).
MS (FD): m/z = 250.1 [C15H10N2O2]+.
HRMS: m/z [M + H]+ calcd for C15H11N2O2: 251.0821; found:
Naphtho[1,8-de]pyrido[3,2-b]iodinin-7-ium Trifluoromethane-
sulfonate (6a) and Naphtho[1,2-d]pyrido[3,2-b]iodolium Tri-
fluoromethanesulfonate (6b)
Iodo compound 5 (2.00 g, 6.04 mmol) was dissolved in CH2Cl2 (20
mL) in a sealed tube under argon. At 0 °C MCPBA (2.07 g, 12.01
mmol) was added, and after stirring for 10 min, TfOH (1.61 mL,
18.12 mmol) was added dropwise. The black solution was stirred
for 1 h and evaporated in vacuo. Et2O was added and the sealed tube
cooled to –25 °C. After 30 min the solid was isolated by suction fil-
tration and washed with cold Et2O to give 6a/6b (ratio 8:1, 1.88 g,
65%) as a yellow solid.
251.0825.
2-(Naphthalen-1-yl)pyridin-3-amine (4)
To 3 (15.00 g, 59.94 mmol) in anhyd THF (100 mL) was added 10%
Pd/C (3.20 g), and the mixture was stirred for 16 h under a H2 atmo-
sphere. The mixture was filtered through celite and the residue
washed with EtOAc. The combined organic layers were washed
with 10% Na2CO3 (15 mL), brine (2 × 20 mL), and dried (MgSO4)
and the solvent was removed. The residue purified by chromatogra-
phy (PE–EtOAc, 3:2) to yield 4 (12.95 g, 98%) as a colorless oil.
IR (neat, ATR): 1608, 1522, 1279, 1214, 1160, 1022, 820, 791, 755
cm–1.
1H NMR COSY, HSQC, HMBC (400 MHz, 100.6 MHz, DMSO-
d6): δ (6a) = 8.98 (dd, J = 7.6, 1.2 Hz, 1 H, 1-CH), 8.79 (dd, J = 4.5,
1.4 Hz, 1 H, 10-CH), 8.51 (dd, J = 8.2, 1.4 Hz, 1 H, 8-CH), 8.29 (dd,
J = 7.6, 1.2 Hz, 1 H, 6-CH), 8.19 (m, 2 H, 4-CH, 3-CH), 7.82 (t,
J = 8.0 Hz, 1 H, 2-CH), 7.68 (t, J = 8.0 Hz, 1 H, 5-CH), 7.57 (dd,
J = 8.2, 4.5 Hz, 1 H, 9-CH).
IR (neat, ATR): 3473, 1611, 1577, 1449, 1309, 1250, 1136, 1017,
971, 906, 799, 778, 764, 727 cm–1.
1H NMR (400 MHz, 100.6 MHz, DMSO-d6): δ (6b) = 9.18 (d, 1 H),
8.79 (dd, 1 H), 8.53 (d, J = 8.2 Hz, 1 H), 8.47 (d, 1 H), 8.22 (1 H,
sup.), 8.09 (t, 2 H), 7.93 (d, 1 H), 7.63 (dd, 1 H).
13C NMR HSQC, HMBC (100.6 MHz, 400 MHz, DMSO-d6): δ
(6a) = 151.9 (d, 10-CH), 147.4 (s, 11a-C), 141.8 (d, 8-CH), 135.1
(s, 3a-C), 132.7 (d, 6-CH), 132.7 (d, 3-CH), 132.2 (d, 4-CH), 130.7
(s, 11b-C), 129.0 (d, 1-CH), 127.9 (d, 5-CH), 127.8 (d, 2-CH), 127.7
(s, 11c-C), 126.0 (d, 9-CH), 102.8 (s, 7a-C), 101.6 (s, 6a-C).
1H NMR (400 MHz, CDCl3): δ = 8.17 (dd, J = 4.6 Hz, J′ = 0.7 Hz,
1 H), 7.91 (m, 2 H), 7.56 (m, 3 H), 7.49 (t, J = 7.2 Hz, 1 H), 7.42 (t,
J = 7.2 Hz, 1 H), 7.15 (dd, J = 8.1 Hz, J′ = 4.6 Hz, 1 H), 7.07 (dd,
J = 4.6, 0.8 Hz, 1 H), 3.56 (br, 2 H).
13C NMR (75 MHz, CDC l3): δ = 144.4 (s), 140.9 (s), 139.5 (d),
135.5 (s), 133.9 (s), 131.0 (s), 128.8 (d), 128.3 (d), 127.1 (d), 126.4
(d), 126.0 (d), 125.7 (d), 125.3 (d), 123.3 (d), 122.1 (d).
MS (FD): m/z (%) = 220.1 (100) [C15H12N2]+.
HRMS: m/z [M + H]+ calcd for C15H13N2: 221.1079; found:
MS (FD): m/z (%) = 330.1 (100), 331.1 (15) [C15H9IN]+.
HRMS: m/z [M]+ calcd for C15H9IN: 329.9780; found: 329.9780.
221.1089.
7-Benzyl-7H-naphtho[1,8-bc][1,5]naphthyridine (7) and 7-Ben-
zyl-7H-benzo[e]pyrido[3,2-b]indole (9)
3-Iodo-2-(naphthalen-1-yl)pyridine (5)
To a solution of p-TsOH (13.0 g, 68.10 mmol) in MeCN (100 mL)
was added 4 (5.00 g, 22.70 mmol). At 10–15 °C, a solution of
NaNO2 (3.13 g) and KI (9.40 g) in H2O was added gradually to the
suspension and stirring was continued for 1 h; the solution was al-
lowed to come to 20 °C. H2O (150 mL) was added and NaHCO3 un-
til pH 9, Na2S2O3 was added to reduce iodine. The mixture was
extracted with Et2O (3 × 30 mL), washed with brine, dried
(MgSO4), and concentrated. Purification by chromatography (PE–
EtOAc, 6:1) afforded pure 5 (3.77 g, 49%) as a pale yellow solid;
mp 108–109 °C.
Pd2(dba)3 (34 mg, 0.04 mmol), Xanthphos (64 mg, 0.11 mmol), and
Cs2CO3 (850 mg, 2.61 mmol) were added to a suspension of 6a/6b
(400 mg, 0.93 mmol) in toluene. After stirring for 5 min, BnNH2
(120 mg) was added and the mixture was stirred overnight at
110 °C. Chromatography (PE–EtOAc, 4:1) gave pure 7 (155 mg,
53% from 6a) as a yellowish solid and the second product 9 (17 mg,
ca. 60%) as a yellow-greenish solid.
7-Benzyl-7H-naphtho[1,8-bc][1,5]naphthyridine (7)
Mp 148–149 °C.
IR (neat, ATR): 1561, 1432, 1419, 1386, 1118, 1065, 1012, 970,
862, 800, 774, 721 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.72 (dd, J = 4.7, 1.6 Hz, 1 H, 6-
CH), 8.32 (dd, J = 8.0, 1.6 Hz, 1 H), 7.93 (m, 2 H), 7.57 (dd, J = 8.2,
7.0 Hz, 1 H), 7.37–7.52 (m, 4 H), 7.10 (dd, J = 8.0, 4.7 Hz, 1 H, 5-
CH).
13C NMR (75 MHz, CDCl3): δ = 162.0 (s), 148.6 (d), 146.9 (d),
140.1 (s), 133.6 (s), 130.9 (s), 128.9 (d), 128.3 (d), 126.7 (d), 126.4
(d), 126.0 (d), 125.3 (d), 125.1 (d), 123.6 (d), 97.1 (s).
IR (neat, ATR): 3057, 2924, 1619, 1590, 1570, 1445, 1433, 1380,
1261, 1152, 1026, 905, 767, 725, 695 cm–1.
1H NMR, COSY, HSQC (400 MHz, 100.6 MHz, CDCl3): δ = 8.27
(dd, J = 7.4, 1.2 Hz, 1 H, 1-CH), 8.20 (dd, J = 4.5, 1.6 Hz, 1 H, 10-
CH), 7.60 (dd, J = 8.2, 1.2 Hz, 1 H, 3-CH), 7.50 (m, 1 H, 2-CH),
7.36 (m, 2 H, CHPh), 7.30 (m, 3 H, CHPh), 7.17 (m, 2 H, 4-CH, 5-
CH), 7.05 (dd, J = 8.2, 4.3 Hz, 1 H, 9-CH), 6.98 (dd, J = 8.4, 1.4 Hz,
1 H, 8-CH), 6.34 (m, 1 H, 6-CH), 5.02 (s, 2 H, CH2).
13C NMR, HSQC(100.6 MHz, 400 MHz, CDCl3): δ = 141.7 (d, 10-
CH), 140.8 (s, 11a-C), 139.7 (s, 6a-C), 137.5 (s, 7a-C), 135.3 (s, 2′-
MS (FD): m/z (%) = 331.0 (100) [C15H10IN]+.
Synthesis 2013, 45, 3173–3178
© Georg Thieme Verlag Stuttgart · New York

PAPER
Naphthonaphthyridine
3177
C),135.2 (s, 3a-C), 130.9 (s, 11b-C), 129.1 (d, 4′-CH), 127.5 (d, 2-
CH), 127.5 (d, 5′-CH), 127.2 (d, 5-CH), 126.2 (d, 3-CH), 126.0 (d,
3′-CH), 125.7 (s, 11c-C), 124.0 (d, 9-CH), 120.1 (d, 8-CH), 118.0
(d, 4-CH), 116.4 (d, 1-CH), 103.9 (d, 6-CH), 50.8 (t, 1′-CH2).
C), 126.9 (d, 2-CH), 123.8 (d, 1-CH), 123.2 (d, 3-CH), 118.6 (d, 9-
CH), 118.4 (d, 8-CH), 113.6 (d, 6-CH), 113.1 (s, 11b-C).
MS (FD): m/z = 218.1 [C15H10N2]+.
FD-MS: m/z (%) = 308.1 (100) [M+]
X-ray Structure Determination of 7
Enraf–Nonius Turbo-Cad 4, equipped with a rotating anode (CuKα,
graphite monochromator; λ = 1.54180 Å). Crystal data: C22H16N2,
M = 308.4 g mol–1, 0.05 × 0.1 × 0.2 mm3, monoclinic, P21/n,
T = 193 K, unit cell: a = 7.603(2) Å, b = 17.772(1) Å, c = 11.613(2)
Å, β = 96.571(10)°, V = 1558.8(5) Å3, z = 4, dcalc = 1.314 g cm–3,
absorption μ = 0.6 mm–1, θ range for data collection: 2–70°; index
ranges: –9 ≤ h ≤ 0, 0 ≤ k ≤ 21, –14 ≤ l ≤ 14. Number of reflections
collected: 3301; independent reflections: 2951 [Rint = 0.0725]. Di-
rect structure solution: program SIR 97, refinement: SHELXL
97,17a full-matrix least squares on 217 parameters, weighted refine-
Anal. Calcd for C22H16N2: C, 85.79; H, 5.23; N, 9.09. Found: C,
85.46; H, 5.02; N, 9.30.
7-Benzyl-7H-benzo[e]pyrido[3,2-b]indole (9)
Mp 133–134 °C.
1H NMR (400 MHz, CDCl3): δ = 9.66 (d, J = 8.5 Hz, 1 H, 1-CH),
8.77 (dd, J = 4.6, 1.6 Hz, 1 H, 10-CH), 8.01 (d, J = 8.0 Hz, 1 H),
7.92 (d, J = 8.8 Hz, 1 H), 7.83 (t, J = 8.6 Hz, 1 H), 7.69 (dd, J = 8.8
Hz, 1 H), 7.57–7.53 (m, 2 H), 7.34 (dd, 1 H), 7.28–7.23 (m, 3 H,
Ph), 7.07 (dd, 2 H), 5.59 (s, 2 H, CH2).
13C NMR, (100.6 MHz, CDCl3): δ = 142.9, 142.6, 139.2, 136.6,
132.8, 129.5 (Cq), 129.2 (CH), 128.9 (2 CH), 128.9, 128.5, 127.8,
127.7 (CH), 126.2 (2 CH), 124.8, 123.8, 118.5, 116.2 (CH), 114.3
(Cq), 110.6 (CH), 436.5 (CH2).
2
2
2
ment: w = 1/[σ2(Fo ) + (0.0826 P)2] with P = [max(Fo ,0) + 2Fo ]/3,
H atoms located from difference Fourier synthesis and refined iso-
tropically assuming a riding motion model, non-hydrogen atoms
improved with anisotropic temperature factors. Goodness-of-fit on
S = 1.013, maximal range of parameters: 0.001(e.s.d.), final R indi-
ces: R1 = 0.1565, wR2 = 0.0522, the final difference Fourier map
showed minimum and maximum values of 0.23 and –0.23 e Å–3, re-
spectively.17b
HRMS: m/z [M + H]+ calcd for C22H17N2: 309.1392; found:
309.1401.
7H-Naphtho[1,8-bc][1,5]naphthyridine (8)
KOt-Bu (200 mg, 2.6 mmol) was added to a solution of 7 (80 mg,
0.36 mmol) in DMSO (2 mL) and at 25 °C, air was bubbled through
the solution; the mixture turned deeply violet. After 10 min, aq
NH4Cl was added and the product extracted with EtOAc (3 ×),
dried, concentrated, and purified by chromatography (PE–EtOAc,
1:1) to give 8 (76 mg, 98%) as a yellowish solid; mp 193 °C (dec).
Acknowledgement
The authors are grateful to Heinrich Kolshorn for inspiring discus-
sions and NMR spectra.
Supporting Information for this article is available online at
IR (neat, ATR): 3186, 1629, 1607, 1566, 1444, 1365, 1302, 1249,
1127, 955, 870, 825, 762, 669 cm–1.
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
m
tgioSrantnugIifoop
r
itmnatr
1H NMR, COSY, HSQC, HMBC (400 MHz, 100.6 MHz, DMSO-
d6): δ = 9.90 (s, 1 H, NH), 8.05 (dd, J = 3.9, 2.0 Hz, 1 H, 10-CH),
7.83 (dd, J = 7.2, 1.2 Hz, 1 H, 1-CH), 7.43 (dd, J = 8.2, 1.0 Hz, 1 H,
3-CH), 7.34 (m, 1 H, 2-CH), 7.16 (m, 3 H, 9-CH, 8-CH, 5-CH), 6.98
(d, J = 7.6 Hz, 1 H, 4-CH), 6.48 (dd, J = 7.4, 1.0 Hz, 1 H, 6-CH).
13C NMR, HSQC, HMBC (100.6 MHz, 400 MHz, DMSO-d6):
δ = 141.3 (d, 10-CH), 138.5 (s, 6a-C), 138.0 (s, 11a-C), 135.9 (s, 7a-
C), 135.5 (s, 3a-C), 131.8 (s, 11b-C), 127.7 (d, 5-CH), 127.6 (d, 2-
CH), 125.1 (d, 3-CH), 124.8 (s, 11c-C), 124.7 (d, 9-CH), 121.4 (d,
8-CH), 115.4 (d, 4-CH), 114.0 (d, 1-CH), 105.5 (d, 6-CH).
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