New series of acridines and phenanthrolines: Synthesis and characterization

Article abstract of DOI:10.1016/j.tet.2014.02.067

New series of acridines and phenanthrolines have been prepared from β-chlorovinyl aldehydes and various aniline derivatives allowing the installation of valuable substituents, such as ketone, nitro or amino groups at the heterocyclic core. X-ray analyses

Full text of DOI:10.1016/j.tet.2014.02.067

Tetrahedron 70 (2014) 3042e3048
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
New series of acridines and phenanthrolines: synthesis and
characterization
,
b
a
a
a
b
Amel Souibgui a , Anne Gaucher , Jerome Marrot , Flavien Bourdreux , Faouzi Aloui ,
ꢀ ^
a,
*
b,
*
ꢀ
Bechir Ben Hassine , Damien Prim
a University of Versailles Saint-Quentin-en-Yvelines, Institut Lavoisier de Versailles UMR CNRS 8180, 45, avenue des Etats-Unis,
78035 Versailles cedex, France
b
ꢁ
ꢀ
ꢁ
ꢀ
Laboratoire de Synthese Organique, Asymetrique et Catalyse Homogene, Faculte des sciences de Monastir, Avenue de l’Environnement,
5019 Monastir, Tunisia
a r t i c l e i n f o
a b s t r a c t
Article history:
New series of acridines and phenanthrolines have been prepared from
b-chlorovinyl aldehydes and
Received 10 January 2014
Received in revised form 11 February 2014
Accepted 24 February 2014
Available online 2 March 2014
various aniline derivatives allowing the installation of valuable substituents, such as ketone, nitro or
amino groups at the heterocyclic core. X-ray analyses confirmed the structures of acridines and phe-
nanthrolines as well as the presence of partially hydrogenated rings and their crucial impact on the
overall shape of the acridine-based architectures. 1H NMR revealed the helical behaviour of several ac-
ridine motives. Comparison of UV data between architectures and influence of number of partially hy-
drogenated rings is also described.
Keywords:
Acridine-based architectures
Phenanthrolines
Ó 2014 Elsevier Ltd. All rights reserved.
1. Introduction
angular topologies.11 The incorporation of a second nitrogen atom
leading to the phenanthroline family and to a new range of specific
Acridine is an aromatic linear tricyclic motif comprising a cen-
tral pyridine and two fused benzene rings. Known for more than
one century, this heterocycle and its derivatives is still of great in-
terest in the scientific community. Indeed, they represent an ap-
pealing structural feature widely occurring in numerous natural
products with biological activities and in medicinal chemistry. For
instance, acridine-based compounds recently showed anti-malar-
ial,1 -microbial,2 -inflammatory,3 -cancer4 and acetylcholinesterase
inhibition5 activities.
The acridine motif can also be found in chemosensors, dyes,
fluorescent probes,6 as ligands in metal-promoted catalysis7 or very
recently in hole transport or chiroptical materials8 and two photon
absorption devices.9 Most of these properties are strongly de-
pendent on the combination of two main factors10 that are (i) the
nature of substituents and their specific interactions with proteins,
lipids, DNA or natural macromolecules and (ii) the crucial role of
the acridine-platform nitrogen atom. Current strategies developed
to increase and/or modulate the aforementioned properties rely
first on the extension of the aromatic motif through additional
benzo- or naphtho-fused rings that may generate various linear and
properties represents a second research line.12 The fine tuning of
the overall flexibility of the acridine platform through in-
corporation of partially hydrogenated cycles within the acridine
core is an additional emerging concern.13 Nevertheless, catalytic
hydrogenation on substituted acridine structures does not neces-
sarily give access to partially hydrogenated moieties. It appears to
be dependent on the position of the substituent.14 A more conve-
nient approach should be the construction of acridine derivatives
from partially saturated precursors. Slight structural modifications
from entirely aromatic to partially hydrogenated shape have been
shown to bring significant changes in pharmaceutical activities2a
and to induce novel photophysical properties.10d,15a Elaboration of
methodologies that allow the joint construction of new acridine-
based topologies, the control of structural parameters, such as the
presence of partially hydrogenated ring and the installation of ad-
ditional nitrogen atoms are challenging and worthwhile.
We have recently reported on the preparation and influence of
structural modulations on photophysical properties of fused fluo-
renones including acridino-fluorenones.16 The high efficiency of
our strategy, encouraged us to explore the construction of new
acridine series that allows (i) the installation of various fused rings
(benzo, dibenzo, naphtho) to the acridine motif, (ii) the regiode-
fined introduction of nitrogen atoms, (iii) the comparison of
physical properties between partially hydrogenated and fully
* Corresponding authors. Tel.: þ33 1 39 25 44 54; fax: þ33 1 39 25 44 52 (D.P.);
tel.: þ216 735 00278 (B.B.H.); e-mail addresses: bechir.benhassine@fsm.mu.tn (B.
Ben Hassine), damien.prim@uvsq.fr (D. Prim).
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.02.067

A. Souibgui et al. / Tetrahedron 70 (2014) 3042e3048
3043
aromatic structures. We thus report herein the preparation of new
acridines as well as [1,7]- and [4,7]-phenanthrolines that in-
corporate partially hydrogenated ring using a single and easy-to-
set strategy (Fig. 1). NMR as well as X-ray support the de-
termination of novel topologies. Comparison of photophysical data
is also given showing the impact of structural modulations on UV/
vis, fluorescence and band gap energies.
Scheme 1. Preparation of various dihydroacridines from b-chlorovinyl aldehyde 1.
Our strategy was next extended to b-chlorovinyl aldehyde 2.
Similar conditions (1 equiv amine, isopropanol) were used for the
preparation of acridine derivatives 4aef. Heating at 150 ꢀC ensured
completion of reactions and high yields of expected products
(Scheme 2).
Fig. 1. Example of targeted acridine-based topologies.
2. Results and discussion
We first started with the preparation of various acridines from
b
-chlorovinyl aldehydes. As recently reported by us,17 aldehydes 1
and 2 were readily obtained from the parent cycloalkanone de-
rivatives (Fig. 2).
Scheme 2. Preparation of various dihydroacridines from b-chlorovinyl aldehyde 2.
Fig. 2. Starting b-chlorovinyl aldehydes.
Reaction of 1-naphthylamine, 1-amino dihydronaphthalene and
1,4-diaminobenzene with 2 afforded acridine derivatives 4a,b and
4d, which are benzofused analogues of 3a,b and 3d, respectively.
This series could be extended to anilines bearing an electron
withdrawing group, such as nitro without significant decrease of
yield. In contrast to 3c, the reaction involving 8-aminotetralone did
not lead to the expected ketone. In fact, 4c was isolated in a fair 58%
yield. No satisfactory explanation could be given for the plausible
overall ‘reductioneelimination’ process observed under such con-
ditions. Single crystals of 3b and 4b were obtained by slow evap-
The reaction of anilines with b-chlorovinyl aldehydes for the
preparation of heterocycles including quinolines and more scarcely
acridines, has already been reported.13d,18 Having in view the con-
struction of elaborated targets, the use of large excess of the
reacting amine (up to 5 equiv) or metal mediated processes as well
as the tedious isolation of the intermediates as stated in these
former studies appeared less attractive and inclined us to revisit the
preparation of acridine-based motives and define our own condi-
tions. Gratifyingly, reaction of equimolar amounts of 1 and various
anilines at 90 ꢀC in isopropanol cleanly afforded the expected ac-
ridines 3.
oration of
a dichloromethane solution. Solid state analysis
The use of concentrations ranging from 0.1 to 0.13 mol Lꢁ1
avoided the formation of side products and limited the purifica-
tion step to a simple filtration or recrystallization (Scheme 1). As
shown in Scheme 1, high to quantitative yields were obtained
regardless of the reacting amine. Indeed, 1-naphthylamine, 1-
confirmed the molecular structure of both acridine derivatives
(Fig. 3).
amino
dihydronaphthalene,
8-aminotetralone,
1,4-
diaminobenzene and 1,3-diaminobenzene afforded compounds
3aee, respectively. Interestingly, no trace of potential bisadduct
was observed when 1 equiv of 1,4-diaminobenzene was used.
Similarly, 3e was obtained as the unique product starting from 1
and 1,3-diaminobenzene. Compound 3e results from a selective
construction of the pyridine ring through preferred cyclization at
the less congested aromatic site. Noteworthy, one or two fused
benzene rings, an additional saturated cycle or functions, such as
amino and ketone groups can be selectively appended to the linear
tricyclic dihydroacridine core.
Fig. 3. X-ray structure determination of 3b (left) and 4b (right).19
Both structures confirm the presence of dihydro units in the
fused polycyclic architecture. The overall architecture displays
a twisted geometry resulting from the presence of one or two
cyclohexyl units. An almost planar central quinoline is

3044
A. Souibgui et al. / Tetrahedron 70 (2014) 3042e3048
accommodated by two cyclohexyl units at each side. Within these
cyclohexyl rings, contiguous methylene carbons lay up and beneath
the median plane of each aromatic fragment, both contributing to
the overall molecular distortion. As shown, the major effect is ob-
served in 4b, which comprises one naphthalene instead of one
benzene unit.
Moving from the partially hydrogenated 4a to the fully aro-
matic 4g through aromatization process impacts the overall
shape of the molecule. Indeed, oxidation process enforces both
methylene carbons to reach a planar shape. Comparison of 1H
NMR spectra of compounds 4a and 4g undoubtedly account for
the evolution of the molecular architecture towards planarity.
Selected 1H NMR data are gathered in Table 1. Interestingly,
chemical shifts for H(1) and H(7) in 3aee and H(1) and H(9) in 4aef
are characteristic of the dihydroacridine substitution pattern. In-
deed, chemical shifts of both H(1) and H(7) in 3aee that arise from
Protons H(9), H(1) and H(15) are privileged spectators vis-a-vis
ꢁ
the evolution of the molecular structure. Indeed, the shielding of
pyridinic H(9) proton Dd
¼
d
[H(9) in 4g]ꢁ
d[H(9) in 4a] is 0.7 ppm.
Noteworthy, fjord region protons H(1) and H(15) undergo dif-
ferently the effect of aromatization process.20 H(1) and H(15) are
shielded by 1.7 and 0.2 ppm, respectively, in good agreement
with an increase of helical behaviour. The large shielding ob-
served for H(1) most likely results from the closer relationship
with the nitrogen lone pair by contrast with H(15). According to
these data, 4g might be considered as an extended aza-helicene
(Fig. 4).
b-chlorovinyl aldehyde 1, are impacted by the presence of strong
electron donating group. A decrease of chemical shifts from 8.68 to
8.51 and 8.54 is observed for NH2 substituents (3d and 3e) by
comparison with cyclohexyl-fused structure 3b. In contrast, in-
stallation of a ketone or an additional aromatic group led to an
increase of the chemical shifts by 0.07 and 0.12 ppm, respectively.
Table 1
We next evaluated the formation of extended architectures
based on a dihydroacridine motif, such as [1,7]- and [4,7]-
phenanthrolines. Advantageously, the preparation of phenanthro-
lines was envisioned through either condensation of amino acri-
Selected characteristic 1H NMR data (
d in ppm) for compounds 3aee and 4aef
dine derivatives 3d, 3e or 4d and an additional equivalent of
chlorovinyl aldehydes or a one pot double condensation using
2 equiv of -chlorovinyl aldehydes and 1 equiv of diaminosubstrate.
Within this context, we first examined the reaction of 3d or 4d with
-chlorovinyl aldehydes 1 or 2. As shown below, this condensation
b-
b
Compound
d
H(1)
d
H(7)
Compound
d
H(1)
9.98
dH(9)
b
3a
3b
3c
3d
3e
8.80
8.68
8.75
8.51
8.54
7.95
7.84
7.86
7.67
7.76
4a
4b
4c
4d
4e
4f
8.08
7.94
7.90
7.88
8.17
8.41
may afford one quinacridine (Fig. 5, top) or one phenanthroline
(Fig. 5, bottom) depending on the cyclisation site.
10.02
9.88
9.58
9.68
9.99
The presence of an additional ring considerably modifies the
1H NMR spectra. Indeed, in each structure H(1) undergo a large
shielding effect plausibly due to the tight relationship with the
nitrogen atom lone pair. dH(1) ranged from 9.58 to 10.02 ppm
evidencing a clear trend to helicity behaviour. In contrast,
chemical shift of the pyridinic H(9) proton appears less affected
by the presence of an additional fused ring. Evolution of the
chemical shifts being related to the nature of the substituents,
similarly to compounds 3. Aromatization by mean of DDQ in
refluxing toluene led to the fully aromatic molecule 4g in a 93%
yield (Fig. 4).
Fig. 5. Envisioned access to quinacridine or phenanthroline starting from 1 and 2.
In fact, this reaction leads only to one product in a high 70%
yield. 1H and 13C NMR confirmed the selective formation of a sym-
metrical phenanthroline showing characteristic signals and shape
of fully symmetrical molecule but did not allow discrimination
between both structures. The structure of 13,14,17,18-
tetrahydronaphtho[2,1-b:10,20-j][4,7]phenanthroline
5 was un-
ambiguously assigned through single crystal X-ray analysis as
shown in Fig. 6.
As already evidenced, the central almost planar phenanthroline
is linked to two benzene rings by saturated cycles partly re-
sponsible for the overall shape of the molecule. Surprisingly, only
compound 6 displays weak
pep interactions. As shown, pep in-
ꢂ
teractions (3.68, 3.63 and 3.79 A) between two terminal naphtha-
lene units and two central heterocycles, respectively, set the design
of trimeric arrangement. Noteworthy, phenanthroline 5 could also
be selectively prepared from 1 and 1,4-diaminobenzene through
sequential addition of the diamine substrate at 90 ꢀC in isopropanol
(Scheme 3). Similarly, phenanthroline 6 could be obtained starting
from 2.
Fig. 4. Aromatization and comparison of 1H NMR spectra between 4a (up) and 4g
(beneath).

A. Souibgui et al. / Tetrahedron 70 (2014) 3042e3048
3045
Fig. 6. Structural determination of 13,14,17,18-tetrahydrodinaphtho[2,1-b:10,20-j][4,7]
phenanthroline 5 (left) and 6 (right).
Fig. 8. UV/vis absorption spectra of various acridines in dichloromethane.
Scheme 3. Synthesis of phenanthroline 5.
b-Chlorovinyl aldehyde 1 was further condensed with 1,3-dia-
minobenzene. Although this condensation may afford one quina-
cridine and one phenanthroline (Fig. 7), only product 7 was isolated
in 29% yield after purification. Careful analysis of 1H NMR spectra
evidenced the presence of singlets resonating at 7.97 and 9.46 ppm
that account for protons H(8) and H(16), respectively. The chemical
shift of H(8) is consistent with those observed for H(7) in com-
pounds 3 (Table 1). Similarly, protons H(4) and H(14) resonate at
8.75 ppm, which is in good agreement with analogous protons in
compounds 3 (Table 1). The large shielding observed for H(16)
Fig. 9. Absorption and emission spectra for compounds 4a and 4g.
(
d
¼9.48 ppm) might plausibly results from the joint contribution of
Both absorption spectra exhibit a set of three bands at 328, 355,
372 nm for 4a and 360, 381, 403 nm for 4g. Emission spectra were
recorded at 328 and 360 nm, respectively, and showed similarly
two sets of three broad bands at 387, 407, 429 and 411, 435, 463.
Bathochromic shifts observed by moving from 4a to 4g are in good
the pyridine ring and the fjord region nitrogen atom lone pair. COSY
as well as NOE experiments show signals characteristic of protons
H(7)eH(6), H(17)eH(16) and H(8)eH(9) relationships and allowed
us to unambiguously assign the structure of phenanthroline 7.
agreement with a concomitant extension of
p conjugation and
lesser spatial deformation. Comparison of absorption and emission
spectra for 5 and 7, which only differ each other by the relative
nitrogen position pattern, is shown in Fig. 9. Phenanthroline 5
displays three absorption bands at 312, 335 and 345 nm and five
emission bands (excitation at 335 nm) at 380, 384, 395, 418 and
447 nm. Moving from the symmetrical [4,7]-phenanthroline 5 to
the non symmetrical [1,7]-phenanthroline 7 led to noticeable
modifications. Indeed, absorption spectra exhibit broad and less
well resolved bands as well as absence of fluorescence (excitation at
338 nm) (Fig. 10).
Fig. 7. Selective access to phenanthroline 7 starting from 1 and 1,3-diaminobenzene.
Absorption spectra of compounds 3a,b and 4a,b were recorded
in dilute dichloromethane solutions (Fig. 8). Marked differences can
be observed moving from 3b, to 3a and further 4a,b.
As expected, the longest-wavelength hyperchromic absorption
maxima of 4a occur at 372 nm. The latter is redshifted by 25 nm
relative to 3a due to the introduction of an additional fused ben-
zene ring unit leading to an extension of the
p conjugation. De-
crease of conjugation either by moving from a naphthalene to
p
a benzene unit (compare 4a to 3a), from a benzoquinoline to
a quinoline (compare 4a to 4b) or combining both (compare 4a to
3b) led to ipsochromic shifts of 25, 17, 22 nm, respectively.
We next compared both UV/vis absorption and emission spectra
of compounds 4a and 4g (Fig. 9).
Fig. 10. Absorption and emission spectra for phenanthrolines 5 and 7.

3046
A. Souibgui et al. / Tetrahedron 70 (2014) 3042e3048
Starting from absorption spectra, we were also able to de-
termine the optical energy band gap (Eg) of acridines and phe-
nanthrolines, 3a,b, 4a,b, 4g, 6 and 7.
The Eg were calculated from the onset of the absorption at
356e479 nm and gathered in Table 2. The UV absorption shows
that 3a,b, 4a,b, 4g, 6, 7 display an Eg ranging from 3.04 to 3.50 eV.
As experimental evidence, we can assume that the Eg values in-
crease, when the number of cycles in the molecule increases.
were collected on a Bruker X8-APEX2 CCD area-detector diffrac-
ꢂ
tometer using Mo K
a
radiation (
l
¼0.71073 A). The structure was
solved by direct methods, developed by successive difference
Fourier syntheses, and refined by full-matrix least-squares on all F2
data using SHELXTL V6.12.
4.2. General procedures for the synthesis of acridines 3e7
Dihydroacridines 3aee: A round-bottom flask was charged un-
der argon with
b-chlorovinyl aldehyde 1 (0.5 mmol), amine
(0.5 mmol) and dry isopropanol (3 mL). The reaction mixture was
stirred and heated 90 ꢀC for 2 h. After coming back to room tem-
perature, the brown coloured organic mass was extracted with
dichloromethane (3ꢂ100 mL) and the layers were separated. The
organic layer was dried over magnesium sulfate and the solvent
was removed under reduced pressure. Thus obtained residue was
subjected to column chromatography purification on silica gel.
Dihydroacridines 4aef: A round-bottom flask was charged under
Table 2
Optical bandgaps for compounds 3ae7
a
Compound
lmax (nm)
lonset (nm)
Eg (eV)
3a
3b
4a
4b
4g
5
347
359
372
355
403
342
382
339
356
375
395
374
410
372
396
392
3.50
3.29
3.13
3.33
3.04
3.35
3.14
3.18
argon with
b-chlorovinyl aldehyde 1 (0.5 mmol), amine
6
7
(0.5 mmol) and dry isopropanol (3 mL). The reaction mixture was
stirred and heated 150 ꢀC for 2 h. After coming back to room
temperature, the brown coloured organic mass was extracted with
dichloromethane (3ꢂ100 mL) and the layers were separated. The
organic layer was dried over magnesium sulfate and the solvent
was removed under reduced pressure. Thus obtained residue was
subjected to column chromatography purification on silica gel.
Acridine 4g: Dihydroacridine 4a (44 mg, 0.13 mmol) and DDQ
(48 mg, 0.21 mmol) were dissolved in toluene (1 mL) and heated at
reflux for 3 h. After cooling to room temperature, the resulting
solution was purified by flash chromatography eluting with pe-
troleum ether/ethyl acetate: 98/02 to yield to acridine 4g as a yel-
low solid (40 mg, 0.121 mmol, 93%).
a
The criterion for reading ‘onset’ wavelengths was that the peak absorbance,
after background (subtraction) correction, should attain 5% of the absorbance of the
lowest-energy wavelength absorption peak.
3. Conclusion
We have developed a rapid and robust strategy to prepare
regiodefined acridines and phenanthrolines using
b-chlorovinyl
aldehydes and various aniline derivatives. X-ray analyses confirmed
the structures of novel acridines and phenanthrolines and high-
lighted the crucial impact of the presence of partially hydrogenated
rings on the overall shape of the acridine-based architectures. 1H
NMR revealed the presence of characteristic shifts that are con-
sistent with a trend towards helicity of acridines. A complete UV/vis
study was also achieved, showing that bathochromic shifts were
depending on the extension of p-conjugation and the modification
of spatial 3D shape of the targets induced by the presence and
number of partially hydrogenated rings.
Dihydroacridines 5e7: A round-bottom flask was charged under
argon with appropriate b-chlorovinyl aldehyde (0.5 mmol), amine
(0.25 mmol) and dry isopropanol (3 mL). The reaction mixture was
stirred and heated 150 ꢀC for 2 h. After coming back to room
temperature, the brown coloured organic mass was extracted with
dichloromethane (3ꢂ100 mL) and the layers were separated. The
organic layer was dried over magnesium sulfate and the solvent
was removed under reduced pressure. Thus obtained residue was
subjected to column chromatography purification on silica gel.
4. Experimental section
4.1. General
4.2.1. 1,2,3,4,8,9-Hexahydrodibenzo[c,h]acridine (3b). After purifi-
cation on silica gel (PE/EtOAc: 90/10), 3b was obtained (135 mg,
90%) as a yellow solid. Mp 128 ꢀC. 1H NMR (300 MHz, CDCl3):
Unless otherwise noted, all starting materials were obtained
from commercial suppliers and used without purification. Petro-
leum ether was distilled under Argon. NMR spectra were recorded
on a 300 MHz and 200 MHz Brucker spectrometers. Chemical shifts
were reported in parts per million relative to the residual solvent
peak (7.27 ppm for CHCl3) for 1H spectra and (77.00 ppm for CDCl3)
for 13C spectra. High Resolution Mass spectroscopy data were
recorded on an Autospec Ultima (Waters/Micromass) device with
a resolution of 5000 RP at 5%. UV/vis analyses were performed on
a PerkineElmer spectrophotometer UV/vis/NIR Lambda 19. A 1 cm
path quartz cells were used for the measurements. Steady-state
fluorescence measurements were recorded on a spectrofluorime-
ter FluoroMax-3 equipped with a 150 W Xenon lamp and a slit
width of 5 nm. For all measurements, the samples used for fluo-
rescence are the same for UV/vis, Infrared spectra were recorded
with an FT spectrometer. Compounds 1, 2 and 3a were prepared
according to literature.13d,17,18 Melting points were determined in
open capillary tubes and are uncorrected. Thin-layer chromatog-
raphy (TLC) was carried out on aluminium sheets precoated with
silica gel 60F254. Column chromatography separations were per-
formed using silica gel (0.040e0.060 mm). X-ray intensity data
d 1.94e2.01 (m, 4H), 2.96e3.14 (m, 6H), 3.52 (br, 2H), 7.20e7.27 (m,
2H), 7.30e7.52 (m, 3H), 7.84 (s, 1H), 8.68 (d, J¼7.5 Hz, 1H). 13C NMR
(75 MHz, CDCl3):
d 23.0, 23.1, 24.7, 28.4, 30.2, 123.8, 125.9, 126.0,
127.1, 127.8, 128.4, 129.1, 129.3, 133.8, 134.8, 135.2,137.2, 139.2, 146.1,
151.5. HRMSeESI: m/z [MþH]þ calcd for C21H20N: 286.1596; found:
286.1592.
4.2.2. 3,4,8,9-Dihydrodibenzo[c,h]acridin-1(2H)-one (3c). After pu-
rification on silica gel (CH2Cl2 and MeOH/CH2Cl2: 50/50), 3c was
obtained (260 mg, 83%) as a black solid. Mp 190 ꢀC. 1H NMR
(300 MHz, CDCl3):
d 2.19e2.27 (m, 2H), 2.83e2.88 (m, 2H),
2.98e3.03 (m, 2H), 3.08e3.13 (m, 4H), 7.23e7.27 (m, 1H), 7.30e7.39
(m, 2H), 7.42e7.47 (m, 2H), 7.79 (d, J¼8.1 Hz, 1H), 7.86 (s, 1H), 8.75
(d, J¼7.3 Hz, 1H). 13C NMR (75 MHz, CDCl3):
d 23.0, 28.2, 28.4, 31.1,
40.9, 126.8, 126.9, 127.1, 127.6 (2), 127.7, 128.5, 129.9, 130.1, 131.8,
133.7,134.8,134.9,139.2,147.9,198.3. HRMSeESI: m/z [MþH]þ calcd
for C21H18NO: 300.1388; found: 300.1391.
4.2.3. 9-Amino-5,6-dihydrobenzo[c]acridine (3d). After purification
on silica gel CH2Cl2, 3d was obtained (115 mg, 89%) as a brown solid.
Mp 52 ꢀC. 1H NMR (300 MHz, CDCl3):
d 2.96e3.09 (m, 4H), 3.85

A. Souibgui et al. / Tetrahedron 70 (2014) 3042e3048
3047
(br, 2H), 6.85 (d, J¼2.2 Hz, 1H), 7.10 (dd, J¼1.8, 8.8 Hz, 1H), 7.24e7.43
NMR (75 MHz, CDCl3):
d
29.0, 29.8, 122.2, 123.5, 125.7 (2), 126.3,
(m, 4H), 7.67 (s, 1H), 7.97 (d, J¼8.9 Hz, 1H), 8.51 (d, J¼7.7 Hz, 1H). 13
C
127.0, 127.7, 128.5, 128.9, 130.7, 131.1, 131.8, 133.9, 134.4, 135.0, 141.3,
145.2, 148.9, 158.2. HRMSeESI: m/z [MþH]þ calcd for C21H15N2O2:
327.1134; found: 327.1127.
NMR (75 MHz, CDCl3):
d 28.4, 28.8, 107.0, 120.8, 125.4, 127.2, 127.8,
128.9, 129.3, 130.9, 131.7, 131.7, 134.8, 138.8, 142.5, 144.4, 149.9.
HRMSeESI: m/z [MþH]þ calcd for C17H15N2: 247.1235; found:
247.1233.
4.2.10. 10,13-Dimethoxy-7,8-dihydronaphtho[2,1-c]acridine
(4f). After purification on silica gel (PE/CH2Cl2: 90/10), 4f was
obtained (65 mg, 93%) as a yellow oil. 1H NMR (300 MHz,
4.2.4. 10-Amino-5,6-dihydrobenzo[c]acridine (3e). After purifica-
tion on silica gel CH2Cl2, 3e was obtained (120 mg, 93%) as a brown
CDCl3):
d
3.1 (br, 4H), 4 (s, 3H), 4.07 (s, 3H), 6.76 (d, J¼9 Hz, 1H),
solid. Mp 86 ꢀC 1H NMR (300 MHz, CDCl3):
d
2.96e3.05 (m, 4H),
6.93 (d, J¼9 Hz, 1H), 7.40 (d, J¼6 Hz, 1H), 7.51 (t, J¼6, 15 Hz, 1H),
3.93 (br, 2H), 6.92 (dd, J¼2.3, 8.7 Hz, 1H) 7.25e7.42 (m, 4H), 7.54
7.65 (t, J¼6, 15 Hz, 1H), 7.85 (t, J¼6, 15 Hz, 1H), 8.41 (s, 1H), 9.99
(d, J¼8.7 Hz, 1H), 7.76 (s, 1H), 8.54 (d, J¼8.7 Hz, 1H). 13C NMR
(d, J¼6 Hz, 1H). 13C NMR (75 MHz, CDCl3):
d 29.1, 30.2, 55.7,
(75 MHz, CDCl3):
d
28.4, 28.5, 109.6, 118.2, 121.8, 125.9, 127.0, 127.1,
56.3, 103.6, 106.4, 120.0, 125.1, 126.2, 127.4, 127.4, 127.9, 128.2,
129.8, 130.3, 131.4, 132.4, 133.9, 139.0, 139.8, 148.2, 150.0, 153.8.
HRMSeESI: m/z [MþH]þ calcd for C23H20NO2: 342.1494; found:
342.1490.
127.8,127.9,129.3,133.6, 134.4,139.4,147.0, 149.1, 153.3. HRMSeESI:
m/z [MþH]þ calcd for C17H15N2: 247.1235; found: 247.1237.
4.2.5. 7,8-Dihydrobenzo[c]naphtho[1,2-h]acridine (4a). After puri-
fication on silica gel (PE/CH2Cl2: 90/10), 4a was obtained (160 mg,
4.2.11. Benzo[c]naphtho[1,2-h]acridine (4g). After purification on
silica gel (PE/ACOEt: 98/02), 4g was obtained (40 mg, 93%) as
58%) as a brown solid. Mp 160 ꢀC. 1H NMR (300 MHz, CDCl3):
d 3.13
(br, 4H), 7.45 (d, J¼8.3 Hz, 1H), 7.55 (m, 1H), 7.68e7.95 (m, 8H), 8.08
a yellow solid. Mp: 190 ꢀC 1H NMR (300 MHz, CDCl3):
d 7.74e7.88
(s, 1H), 9.40 (d, J¼8.1 Hz, 1H), 9.98 (d, J¼8.7 Hz, 1H). 13C NMR
(m, 4H), 7.91e8.11 (m, 8H), 8.69 (s, 1H), 9.62 (d, J¼8 Hz, 1H), 11.57
(75 MHz, CDCl3):
d
28.8, 30.1, 124.6, 124.8, 125.2, 126.4, 127.0, 127.1,
(d, J¼8.8 Hz, 1H). 13C NMR (75 MHz, CDCl3):
d 124.2, 125.3, 125.7,
127.4,127.5, 127.6, 127.8 (2),128.3,130.1 (2), 131.1,131.9, 133.2, 133.4,
126.1,126.6,126.7,127.0,127.2,127.4,127.8,128.1,128.4,128.5,128.5,
130.0, 131.7, 130.8, 131.7, 132.2, 133.7, 134.1, 134.1, 135.1, 146.1, 147.5.
HRMSeESI: m/z [MþH]þ calcd for C25H18N: 330.1283; found:
330.1280.
133.5, 134.0, 139.8, 144.5, 153.2. HRMSeESI: m/z [MþH]þ calcd for
C
25H18N: 332.1439; found: 332.1429.
4.2.6. 7,8,12,13,14,15-Hexahydrobenzo[c]naphtho[1,2-h]acridine
(4b). After purification on silica gel (PE/CH2Cl2: 90/10), 4b was
obtained (110 mg, 80%) as a brown solid. Mp: 150 ꢀC. 1H NMR
4.2.12. 13,14,17,18-Dihydrodinaphtho[2,1-b:10,20-j][4,7]phenanthro-
line (5). After purification on silica gel (PE/CH2Cl2: 50/50), 5 was
obtained (250 mg, 70%) as a yellow solid. Mp 260 ꢀC. 1H NMR
(300 MHz, CDCl3):
d 1.94e2.01 (m, 4H), 2.95e2.99 (m, 2H), 3.07
(br, 4H), 3.49e3.53 (m, 2H), 7.24e7.27 (m, 1H), 7.42 (d, J¼8.1 Hz,
(300 MHz, CDCl3):
d 3.05e3.09 (m, 2H), 3.21e3.26 (m, 2H),
1H), 7.49e7.55 (m, 2H), 7.61e7.66 (m, 1H), 7.88 (t, J¼8.4, 9.4 Hz, 2H),
7.28e7.47 (m, 3H), 8.08 (s, 1H), 8.28 (s, 1H), 8.62 (d, J¼9.4 Hz, 1H).
7.94 (s, 1H), 10.02 (d, J¼6 Hz, 1H). 13C NMR (75 MHz, CDCl3):
d
23.1,
13C NMR (75 MHz, CDCl3):
d 28.2, 28.9, 123.6, 126.0, 127.4, 128.0,
23.2, 25.1, 28.9, 30.2, 30.3, 123.6, 125.0, 125.1, 126.4, 126.7, 127.9,
128.2, 128.6, 130.0, 130.3, 131.1, 131.5, 133.1, 133.9, 135.1, 137.2, 139.9,
145.9, 153.3. HRMSeESI: m/z [MþH]þ calcd for C25H22N: 336.1752;
found: 336.1747.
129.9, 130.8, 139.1. HRMSeESI: m/z [MþH]þ calcd for C28H21N2:
385.1705; found: 385.1705.
4.2.13. 17,18,21,22-Tetrahydro[3,4-b:40,30-j][4,7]phenanthroline
(6). After purification on silica gel (PE/CH2Cl2: 50/50), 6 was
obtained (35 mg, 88%) as a white solid. Mp 265 ꢀC. 1H NMR
4.2.7. 7,8,12,13-Dihydrobenzo[c]naphtho[1,2-h]acridine (4c). After
purification on silica gel (PE/CH2Cl2: 90/10), 4c was obtained
(80 mg, 58%) as a brown solid. Mp: 138 ꢀC. 1H NMR (300 MHz,
(300 MHz, CDCl3):
d
3.13e3.21 (m, 4H), 7.45 (d, J¼8.3 Hz, 1H),
7.54 (t, J¼7.3, 14.8 Hz, 1H), 7.69 (t, J¼7.8, 15.2 Hz, 1H), 7.88e7.92
CDCl3): d 2.45e2.51 (m, 2H), 2.99e3.07 (m, 6H), 6.26e6.32 (m, 1H),
(m, 2H), 8.38 (s, 1H), 8.77 (s, 1H), 9.87 (d, J¼8.7 Hz, 1H). 13C NMR
7.33 (d, J¼8.1 Hz, 1H), 7.42 (d, J¼8.1 Hz, 1H), 7.50e7.68 (m, 3H),
(75 MHz, CDCl3): d 29.4 (2), 30.1 (2), 122.7 (2), 126.3 (2), 126.4 (2),
7.85e7.95 (m, 4H), 9.88 (d, J¼8.7 Hz, 1H). 13C NMR (75 MHz, CDCl3):
127.3 (2), 127.3 (2), 128.3 (2), 128.5 (2), 129.5 (2), 130.5 (2), 131.1
(2), 131.3 (2), 133.2 (2), 134.0 (2), 139.9 (2), 146.1 (2), 154.7 (2).
HRMSeESI: m/z [MþH]þ calcd for C36H25N2: 485.2018; found:
485.2013.
d
23.1, 28.1, 29.0, 30.3, 123.7, 124.8, 125.2, 125.9, 126.4, 126.9, 127.2,
127.8,128.3,128.9,130.2,130.3,131.1,131.2, 131.8, 133.0,133.9, 135.3,
140.1, 142.7, 153.8. HRMSeESI: m/z [MþH]þ calcd for C25H20N:
334.1596; found: 334.1594.
4.2.14. 9,10,17,18-Dihydrodinaphtho[1,2-b:10,20-j][1,7]phenanthroline
(7). After purification on silica gel (PE/CH2Cl2: 90/10), 7 was ob-
tained (54 mg, 29%) as a yellow solid. Mp: 92 ꢀC. 1H NMR (300 MHz,
4.2.8. 11-Amino-7,8-dihydronaphtho[2,1-c]acridine (4d). After pu-
rification on silica gel CH2Cl2, 4d was obtained (54 mg, 83%) as
a brown solid. Mp: 152 ꢀC. 1H NMR (200 MHz, CDCl3):
d
3.03
CDCl3): d 3.04e3.11 (m, 4H), 3.16e3.20 (m, 2H), 3.29e3.33 (m, 2H),
(br, 4H), 6.92 (d, J¼2.6 Hz, 1H), 7.16 (dd, J¼2.6, 7.1 Hz, 1H),
7.37e7.50 (m, 2H), 7.53e7.67 (m, 1H), 7.79e7.88 (m, 3H), 8.17
(d, J¼8.4 Hz, 1H), 9.58 (d, J¼8.8 Hz, 1H). 13C NMR (75 MHz, CDCl3):
7.31 (d, J¼7.4 Hz, 1H), 7.38e7.52 (m, 4H), 7.84 (d, J¼8.9, 1H), 7.97
(s,1H), 8.16 (d, J¼8.9,1H), 8.67 (d, J¼7.4,1H), 8.75 (d, J¼7.5,1H), 9.48
(s, 1H). 13C NMR (300 MHz, CDCl3):
d 28.2, 28.3, 28.5, 28.8, 125.4,
d
29.2, 30.1, 106.9, 121.0, 125.3, 126.2, 127.1, 127.2, 128.3, 128.5,
125.8, 126.1, 126.3, 127.2, 127.3, 127.9, 128.0, 128.8 (2), 129.6, 129.9,
130.1, 130.8, 131.0, 131.2, 131.4, 134.1, 134.8, 139.1, 139.4, 144.2, 152.1,
153.3. HRMSeESI: m/z [MþH]þ calcd for C28H21N2: 385.1705;
found: 385.1710.
129.7, 129.8, 130.1, 130.9, 131.0, 131.7, 133.3, 133.9, 134.5, 139.7,
144.9. HRMSeESI: m/z [MþH]þ calcd for C21H17N2: 297.1392;
found: 297.1392.
4.2.9. 11-Nitro-7,8-dihydronaphtho[2,1-c]acridine (4e). After purifi-
cation on silica gel CH2Cl2, 4e was obtained (110 mg, 82%) as a yel-
Acknowledgements
low solid. Mp 200 ꢀC. 1H NMR (200 MHz, CDCl3):
d
3.13 (br, 4H), 7.44
The authors are grateful to Direction Generale de la Recherche
ꢀ ꢀ
(d, J¼8.3 Hz, 1H), 7.54 (t, J¼6.9, 14.9 Hz, 1H), 7.67 (tdd, J¼1.2, 8.5 Hz,
Scientifique of the Tunisian Ministry of Higher Education and Sci-
entific Research, to the CNRS and the University of Versailles-St
Quentin-en-Yvelines for financial support.
1H), 7.92 (t, J¼8, 16 Hz, 2H), 8.17 (s, 1H), 8.31 (d, J¼9.2 Hz, 1H), 8.42
(d, J¼2.4 Hz, 1H), 8.74 (d, J¼2.3 Hz, 1H), 9.68 (d, J¼8.7 Hz, 1H). 13
C

3048
A. Souibgui et al. / Tetrahedron 70 (2014) 3042e3048
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