Scandium(III) Triflate-Catalyzed Reaction of Aroyl-Substituted Donor-Acceptor Cyclopropanes with 1-Naphthylamines: Access to Dibenzo[ c, h]acridines

Article abstract of DOI:10.1021/acs.joc.0c02105

The reaction of aroyl-substituted donor-acceptor (D-A) cyclopropanes with two equivalents of 1-naphthylamines in the presence of a catalytic amount of scandium(III) triflate provides access to dibenzo[c,h]acridines. The key steps of the transformation are the formation of nucleophilic ring-opening products from the D-A cyclopropanes and 1-naphthylamines and their subsequent fragmentation and cyclization. The method has a reasonable substrate scope, and the products are formed in 50-70% yields.

Full text of DOI:10.1021/acs.joc.0c02105

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Scandium(III) Triflate-Catalyzed Reaction of Aroyl-Substituted
Donor−Acceptor Cyclopropanes with 1‑Naphthylamines: Access to
Dibenzo[c,h]acridines
Murugesan Thangamani and Kannupal Srinivasan*
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ABSTRACT: The reaction of aroyl-substituted donor−acceptor
(D−A) cyclopropanes with two equivalents of 1-naphthylamines in
the presence of a catalytic amount of scandium(III) triflate
provides access to dibenzo[c,h]acridines. The key steps of the
transformation are the formation of nucleophilic ring-opening
products from the D−A cyclopropanes and 1-naphthylamines and
their subsequent fragmentation and cyclization. The method has a
reasonable substrate scope, and the products are formed in 50−70% yields.
fonic acid-mediated electrophilic cycloisomerization of 2,6-
diaryl-3,5-diynylpyridines.12
onor−acceptor (D−A) cyclopropanes are renowned
Dbuilding blocks in organic synthesis, which could be
ingeniously exploited for the synthesis of various carbocyclic,
heterocyclic, and acyclic compounds.1 They usually undergo
three types of reactions, namely, annulation, ring opening, and
ring expansion reactions. Among those reactions, their ring-
opening reactions with N-nucleophiles serve as versatile tools
for the access of a variety of N-containing cyclic and acyclic
products.1d,2
Acridines are one of the important heterocyclic compounds
that have received huge attention, owing to their assortment of
applications in various fields. The acridine motif is found in a
large number of bioactive natural products such as cytotoxic
cystodytins A−K, neurogenin2 promoting insubosins A−C, and
antibacterial xanthacridone.3 Many acridine derivatives also
display a wide range of pharmaceutical activities, and some of
them, such as amsacrine, pyronaridine, and quinacrine, serve as
antineoplastic, antimalarial, and antiprotozoal drugs, respec-
tively.4 Many acridine derivatives also find application as
photocatalysts,5 functional materials,6 and fluorescent dyes to
study cellular processes.7 The significance of acridine
derivatives has acted as a stimulus for the development of
numerous methods for their synthesis,8 in addition to classical
methods.9
Our research group is interested in exploring the synthetic
potentials of trans-2-aroyl-3-arylcyclopropane-1,1-dicarboxy-
lates 1 (Scheme 1; also termed as aroyl-substituted D−A
cyclopropanes).13 Recently, we reported the ring-opening
reactions of 1 with hydrazines for the access of dihydropyr-
azoles 2 and cyclopropane-fused pyridazinones 3 [Scheme
1a].13d In continuation of the work, we became interested in
studying their ring-opening reactions with various amines with
a view to obtain useful nitrogen-containing compounds.
Although many of those reactions gave complicated mixtures
(with amines such as aniline, 2-, 3-, or 4-methylaniline and 2-
naphthylamine), we found that the scandium(III) triflate-
catalyzed reaction of the cyclopropane dicarboxylates 1 and
also related trans-2-aroyl-3-styrylcyclopropane-1,1-dicarboxy-
lates 4 with 1-naphthylamines 5 provide access to various
dibenzo[c,h]acridines 6 [Scheme 1b]. We believe that the
unexpected formation of the products coupled with the
availability of only limited methods for the synthesis of such
compounds compensates for the lack of atom economy in the
reaction. It may also be noted that arylamine acting as a C-
nucleophile for the ring opening of D−A cyclopropanes is rare
in the literature.2e
We began the study by taking the reaction of cyclopropane
dicarboxylate 1a with 1-naphthylamine (5a) as a model
reaction to identify optimal reaction conditions (Table 1).
Among various acridines, dibenzo[c,h]acridines exhibit
unique photophysical properties, and hence, they are
considered promising OLED materials.10 Despite their
importance, only sporadic reports are available for the
synthesis of dibenzo[c,h]acridines in the literature, and they
often involve multistep procedures.10,11 So alternate strategies
for the access of dibenzo[c,h]acridines are necessary. Recently,
Langer and co-workers have developed a convenient procedure
for the access of dibenzo[c,h]acridines through methanesul-
Received: September 1, 2020
https://dx.doi.org/10.1021/acs.joc.0c02105
© XXXX American Chemical Society
J. Org. Chem. XXXX, XXX, XXX−XXX
A

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Note
Scheme 1. Ring-Opening Reactions of Aroyl-Substituted D−A Cyclopropanes with (a) Hydrazines and (b) 1-Naphthylamines
(entry 8). At the same time, increasing the amount of catalyst
to 20 mol % decreased the yield of 6a to 52% due to the
formation of more impurities (entry 9). The reaction did not
take place when a catalytic or stoichiometric amount of AlCl3,
SnCl4, and BF3·OEt2 was used as Lewis acids, possibly due to
the strong coordination of these Lewis acids to 1-naphthyl-
amine (6a) (entry 10). Other triflate catalysts, such as
copper(II) triflate, indium(III) triflate, and ytterbium(III)
triflate and a Bronsted acid, p-TsOH, were ineffective for
catalyzing the reaction (entry 11). Further, the reaction did not
take place in other solvents such as THF, EtOH, and
nitromethane (entry 12). So, we selected heating 1 equiv of
cyclopropane dicarboxylate 1a with 2 equiv of 1-naphthyl-
amine (5a) in toluene under reflux as optimal conditions for
the formation of dibenzo[c,h]acridine 6a.
Adapting the optimized reaction conditions, we first probed
the scope of the reaction for various trans-2-aroyl-3-
arylcyclopropane-1,1-dicarboxylates and 1-naphthylamines
(Table 2). Since the aroyl group of the cyclopropane is lost
during the course of the reaction, we observed that both
cyclopropane dicarboxylates 1a (Ar1 = Ar2 = Ph) and 1b (Ar1
= Ph and Ar2 = 4-MeC6H4) gave the same dibenzo[c,h]-
Table 1. Optimization of the Reaction Conditions
S.
No.
yield of
a
reagents and conditions
6a (%)
b
1
5a (1 equiv), Sc(OTf)3 (10 mol %), DCM, rt or reflux,
24 h
NR
b
2
5a (1 equiv), Sc(OTf)3 (10 mol %), 1,2-DCE, rt or reflux,
24 h
NR
b
3
4
5
6
7
8
9
5a (1 equiv), Sc(OTf)3 (10 mol %), PhMe, rt, 24 h
5a (1 equiv), Sc(OTf)3 (10 mol %), PhMe, reflux, 12 h
5a (2 equiv), Sc(OTf)3 (10 mol %), PhMe, reflux, 10 h
5a (3 equiv), Sc(OTf)3 (10 mol %), PhMe, reflux, 10 h
5a (2 equiv), Sc(OTf)3 (10 mol %), PhMe, 80 °C, 12 h
5a (2 equiv), Sc(OTf)3 (5 mol %), PhMe, reflux, 10 h
5a (2 equiv), Sc(OTf)3 (20 mol %), PhMe, reflux, 10 h
NR
30
68
66
55
40
52
b
10 5a (2 equiv), AlCl3, SnCl4 or BF3·OEt2 (10 mol % or 1
equiv), PhMe, reflux, 12 h
11 5a (2 equiv), Cu(OTf)2, In(OTf)3, Yb(OTf)3 or p-TsOH
(10 mol %), PhMe, reflux, 12 h
12 5a (2 equiv), Sc(OTf)3 (10 mol %), THF, EtOH or
MeNO2, reflux, 12 h
NR
b
NR
b
NR
Table 2. Scope of the Reaction for Various trans-2-Aroyl-3-
arylcyclopropane-1,1-dicarboxylates and 1-Naphthylamines
a
b
Isolated yield. No reaction.
Initially, we selected scandium(III) triflate as a catalyst for the
reaction, owing to its tendency of weakly coordinating with
amines14 and also its widespread use in D−A cyclopropane
chemistry.1 When the reaction was conducted in the presence
of 10 mol % of scandium(III) triflate using DCM or 1,2-DCE
as a solvent, the reactions did not materialize at room
temperature as well as under refluxing conditions (Table 1,
entries 1 and 2). When toluene was used as a solvent, the
reaction did not take place even after 24 h at room temperature
(entry 3). However, the reaction afforded dibenzo[c,h]acridine
6a in 30% yield when heated under reflux for 12 h (entry 4)
(the structure of 6a was confirmed by X-ray crystallographic
analysis15). The yield of 6a increased to 68% when 2 equiv of
5a was used in the reaction (entry 5). However, the use of 3
equiv of 5a did not alter the yield of 6a significantly (entry 6).
When the temperature of the reaction (using two equivalents
of 5a) was reduced to 80 °C, the yield of 6a was also reduced
to 55% (entry 7). When the amount of catalyst in the reaction
was reduced to 5 mol %, the yield of 6a decreased to 40%
a
entry
Ar1, Ar2
R
yield of 6 (%)
b
1
2
3
4
5
6
7
8
Ph, Ph (1a)
H (5a)
H (5a)
H (5a)
H (5a)
H (5a)
H (5a)
H (5a)
Br (5b)
Br (5b)
Br (5b)
NO2 (5c)
68 (6a)
62 (6a)
70 (6b)
66 (6c)
63 (6d)
c
60 (6e)
66 (6f)
62 (6g)
50 (6h)
52 (6i)
Ph, 4-MeC6H4 (1b)
4-MeC6H4, Ph (1c)
4-MeOC6H4, Ph (1d)
4-ClC6H4, Ph (1e)
4-O2NC6H4, Ph (1f)
1-Naphthyl, Ph (1g)
Ph, Ph (1a)
4-MeC6H4, Ph (1c)
4-NO2C6H4, Ph (1f)
Ph, Ph (1a)
9
10
11
a
b
c
Isolated yield. cis-Isomer of 1a also forms 6a in 63% yield. Could
not be isolated in pure form.
B
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acridine 6a with 1-naphthylamine (5a) (Table 2, entries 1 and
2). So we decided to vary only the Ar1 ring of the
cyclopropanes for further experiments. The reaction tolerates
cyclopropane dicarboxylates 1c−e having electron-donating
and halogen-containing aryl rings such as p-tolyl, p-anisyl, and
p-chlorophenyl rings as Ar1and the respective dibenzo[c,h]-
acridines 6b−d are produced in 63−70% yields (entries 3−5).
Although the reaction took place when the p-nitrophenyl ring
was used as Ar1, the respective dibenzo[c,h]acridine could not
be isolated in pure form (entry 6). When cyclopropane
dicarboxylate 1g possessing bulky 1-naphthyl ring as Ar1 was
used, the reaction afforded the corresponding dibenzo[c,h]-
acridine 6e in 60% yield (entry 7). We also reacted
cyclopropane dicarboxylates 1a, 1c, and 1f with 4-bromo-1-
naphthylamine (5b) and obtained the respective dibenzo[c,h]-
acridines 6f−h in 50−66% yields (entries 8−10). It is
interesting to note that the presence of bromo substituents
in the products 6f−h would allow further synthetic elaboration
through palladium chemistry. We also tested the reaction of
cyclopropane dicarboxylate 1a with 4-nitro-1-naphthylamine
(5c), and the reaction also afforded the corresponding
dibenzo[c,h]acridine 6i in 52% yield (entry 11).
fragmentation with BF3·OEt2 to yield benzaldehyde and
phenacyl malonate (7). So, we infer that a similar
fragmentation is possible in the present transformation as
well when the putative 1,3-zwitterionic intermediate from the
cyclopropane captures the nucleophile (1-naphthylamine).16
The absence of aroyl and diester moieties in the products also
supports this point. Accordingly, we propose a plausible
mechanism outlined in Scheme 2 for the formation of
dibenzo[c,h]acridines in the present reactions, by taking the
reaction between 1a and 2a as a representative example. In the
presence of Sc(OTf)3 (LA), 1-naphthylamine (5a) acts as a C-
nucleophile and attacks the cyclopropane dicrboxylate 1a at
the carbon bearing the donor group to give intermediate A,
which upon rearomatization produces the adduct B. The
adduct B then undergoes fragmentation to form the
intermediate C by eliminating phenacyl malonate (7). The
intermediate C is further attacked by another molecule of 1-
naphthylamine (5a), resulting in intermediate D. The
electrocyclic ring closure of D with a loss of ammonia gives
intermediate E, which finally undergoes aromatization with a
loss of hydrogen to afford dibenzo[c,h]acridine 6a. It may be
noted that we are not able to isolate the eliminated phenacyl
malonate (7) from the reaction mixture, possibly due to its
untraceable reaction with 1-naphthylamine (5a). It is also
noteworthy that the reaction of benzaldehyde or 1,3-dioxolane-
protected benzaldehyde with 5a does not give any trace of
dibenzo[c,h]acridine 6a under the current reaction conditions.
In summary, we have synthesized a series of dibenzo[c,h]-
acridines through the scandium(III) triflate-catalyzed reaction
of aroyl-substituted D−A cyclopropanes with 1-naphthyl-
amines. The reaction proceeds through the ring opening of
cyclopropane, the addition of naphthylamine, fragmentation of
resulting intermediate, and subsequent cyclization. Given the
limited methods available for the access of dibenzo[c,h]-
acridines, the current method is a valuable addition to the
existing methods.
Next, we extended the scope of the reaction to another type
of aroyl-substituted D−A cyclopropanes 4, having the styryl
moiety as a donor group, in order to see whether the presence
of a vinyl unit has any effect on the outcome of the reaction
(Table 3). Nevertheless, these styrylcyclopropane dicarbox-
Table 3. Scope of the Reaction for Various trans-2-Aroyl-3-
styrylcyclopropane-1,1-dicarboxylates and 1-
Naphthylamines
a
EXPERIMENTAL SECTION
entry
Ar1, Ar2
Ph, Ph (4a)
4-MeOC6H4, Ph (4b)
2-Thienyl, Ph (4c)
Ph, Ph (4a)
2-Naphthyl, Ph (4d)
2-Thienyl, Ph (4c)
Ph, Ph (4a)
R
yield of 6 (%)
■
General Remarks. Melting points were determined by the open
1
2
3
4
5
6
7
H (5a)
H (5a)
H (5a)
Br (5b)
Br (5b)
Br (5b)
NO2 (5c)
70 (6j)
60 (6k)
62 (6l)
60 (6m)
66 (6n)
60 (6o)
61 (6p)
capillary tube method and are uncorrected. The H and 13C NMR
1
spectra were recorded on a 400 MHz NMR spectrometer. High-
resolution mass spectra (ESI) were recorded on a Q-Tof mass
spectrometer. Low-resolution mass spectra (ESI) were recorded on an
LC−MS spectrometer. Elemental analyses were performed on a CHN
analyzer. X-ray crystallographic data were collected on a CCD
diffractometer using graphite-monochromated Mo Kα radiation.
Thin-layer chromatography (TLC) was performed on precoated
alumina sheets and detected under UV light. Silica gel (100−200
mesh) was used for column chromatography. The starting materials,
trans-2-aroyl-3-aryl/styrylcyclopropane-1,1-dicarboxylates 1 and 4,
were prepared as per our earlier reports.13b,e
a
Isolated yield.
ylates 4 also exhibited a similar pattern of reactivity as their
sister substrates. Thus, cyclopropane dicarboxylates 4a−d
having phenyl, p-anisyl, 2-thienyl, and 1-naphthyl rings
attached to the vinyl unit gave the expected dibenzo[c,h]-
acridines 6j−p in 60−70% yields upon reaction with 1-
naphthylamine (5a), 4-bromo-1-naphthylamine (5b), and 4-
nitro-1-naphthylamine (5c) (entries 1−7).
We have previously reported that diethyl trans-2-benzoyl-3-
styrylcyclopropane-1,1-dicarboxylate 4a when treated with
BF3·OEt2 in DCM undergoes ring opening to give the
corresponding putative 1,3-zwitterionic intermediate, which
captures H2O (from moisture) and undergoes fragmentation
to yield cinnamaldehyde and phenacyl malonate (7).13e We
have also observed that diethyl trans-2-benzoyl-3-phenyl-
cyclopropane-1,1-dicarboxylate 1a also undergoes similar
General Procedure for the Synthesis of Acridines 6a−p. To
a solution of trans-2-aroyl-3-aryl/styryl-cyclopropane-1,1-dicarboxy-
late 1/4 (1.0 mmol) in toluene (5 mL) were added 1-naphthylamine
2 (2.0 mmol) and Sc(OTf)3 (49 mg, 10 mol %), and the reaction
mixture was heated in an oil bath under reflux for 8−10 h. After the
reaction was complete (monitored by TLC), the reaction mixture was
quenched with water and extracted with ethyl acetate. The combined
organic layers were washed with brine, dried over anhydrous Na2SO4,
and evaporated under a vacuum. The crude product was purified by
column chromatography on silica gel using ethyl acetate/hexane (1:9)
as the eluent to give pure acridine 6.
7-Phenyldibenzo[c,h]acridine (6a).8a Yellow solid. Yield: 241 mg
(68%). Mp: 208−212 °C. Rf: 0.65 (EtOAc/hexane, 1:19 v/v). H
NMR (400 MHz, CDCl3): δ 9.82 (d, J = 8.0 Hz, 2H), 7.90−7.83 (m,
1
C
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Scheme 2. Mechanism for the Formation of Dibenzo[c,h]acridines (LA Coordination to Malonate Moiety Is Not Shown in
Intermediate Structures for Clarity)
4H), 7.77−7.23 (m, 2H), 7.68−7.59 (m, 5H), 754−7.52 (m, 2H),
7.48−7.46 (m, 2H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ
145.8, 145.5, 136.6, 133.5, 132.1, 130.6, 128.7, 128.6, 128.2, 127.8,
127.4, 127.2, 125.5, 124.0, 123.7 ppm. HRMS (ESI-TOF) m/z: [M+
H]+ calcd for C27H18N, 356.1434; found, 356.1440.
5,9-Dibromo-7-(p-tolyl)dibenzo[c,h]acridine (6g). Yellow liquid.
Yield: 327 mg (62%). Rf: 0.56 (EtOAc/hexane, 1:19 v/v). H NMR
1
(400 MHz, CDCl3): δ 9.88 (d, J = 8.0 Hz, 2H), 7.96−7.88 (m, 2H),
7.82−7.80 (m, 2H), 7.74−7.71 (m, 2H), 7.64−7.61 (m, 2H), 7.50−
7.48 (m, 2H), 7.42−7.40 (m, 2H), 2.60 (s, 3H) ppm; 13C{1H} NMR
(100 MHz, CDCl3): δ 146.0, 145.5, 138.0, 133.6, 132.1, 130.5, 129.2,
128.7, 127.7, 127.2, 127.1, 125.5, 124.2, 123.8, 21.5 ppm; HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C28H18Br2N, 525.9800; found,
525.9797.
5,9-Dibromo-7-(4-nitrophenyl)dibenzo[c,h]acridine (6h). Pale
yellow liquid. Yield: 279 mg (50%). Rf: 0.18 (EtOAc/hexane, 1:19
v/v). 1H NMR (400 MHz, CDCl3): δ 9.78−9.68 (m, 2H), 8.26−8.24
(m, 1H), 7.82−7.68 (m, 5H), 7.61−7.54 (m, 3H), 7.43−7.37 (m,
3H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ 145.1, 144.7, 135.9,
133.6, 133.0, 132.0, 130.5, 128.8, 127.9, 127.5, 125.7, 125.5, 124.0,
123.9, 122.6 ppm. MS (ESI) m/z: 573.43 [M + NH4]+. Anal. Calcd
for C27H14Br2N2O2: C, 58.09; H, 2.53; N, 5.02. Found: C, 58.33; H,
2.60; N, 5.10.
7-(p-Tolyl)dibenzo[c,h]acridine (6b). Pale yellow solid. Yield: 258
mg (70%). Mp: 210−214 °C. Rf: 0.42 (EtOAc/hexane, 1:19 v/v). 1H
NMR (400 MHz, CDCl3): δ 9.82 (d, J = 8.4 Hz, 2H), 7.90−7.82 (m,
4H), 7.76−7.72 (m, 2H), 7.68−7.65 (m, 2H), 7.58−7.56 (m, 2H),
7.44−7.42 (m, 2H), 7.36−7.35 (m, 2H), 2.54 (s, 3H) ppm. 13C{1H}
NMR (100 MHz, CDCl3): δ 146.0, 145.5, 138.0, 133.6, 133.5, 132.1,
130.5, 129.2, 128.7, 127.7, 127.2, 127.1, 125.5, 124.2, 123.8, 21.5
ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C28H20N,
370.1590; found, 370.1597.
7-(4-Methoxyphenyl)dibenzo[c,h]acridine (6c).8a Pale yellow
solid. Yield: 254 mg (66%). Mp: 209−211 °C. Rf: 0.44 (EtOAc/
1
hexane, 1:19 v/v). H NMR (400 MHz, CDCl3): δ 9.48 (d, J = 8.0
Hz, 1H), 8.30 (d, J = 8.8 Hz, 3H), 8.16 (d, J = 8.4 Hz, 1H), 7.89−
7.82 (m, 3H), 8.00−7.65 (m, 6H), 7.07 (d, J = 8.8 Hz, 2H), 3.89 (s,
3H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ 160.8, 155.2, 146.2,
136.5, 133.9, 132.5, 128.9, 128.1, 127.8, 127.0, 126.8, 125.2, 124.7,
118.3, 114.2, 55.5 ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C28H20NO, 386.1539; found, 386.1545.
7-(4-Chlorophenyl)dibenzo[c,h]acridine (6d). Yellow solid. Yield:
245 mg (63%). Mp: 214−216 °C. Rf: 0.50 (EtOAc/hexane, 1:19 v/v).
1H NMR (400 MHz, CDCl3): δ 9.81 (d, J = 8.4 Hz, 2H), 7.89−7.84
(m, 6H), 7.67−7.59 (m, 4H), 7.53−7.51 (m, 2H), 7.47−7.46 (m,
2H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ 145.5, 144.3, 135.0,
134.4, 133.5, 131.99, 131.96, 128.9, 128.8, 127.8, 127.7, 127.3, 125.5,
123.6, 123.5 ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C27H17ClN, 390.1044; found, 390.1048.
7-(Naphthalen-1-yl)dibenzo[c,h]acridine (6e). Yellow solid. Yield:
243 mg (60%). Mp: 210−214 °C. Rf: 0.48 (EtOAc/hexane, 1:19 v/v).
1H NMR (400 MHz, CDCl3): δ 9.88 (d, J = 8.0 Hz, 2H), 8.10−8.01
(m, 2H), 7.88−7.84 (m, 4H), 7.76−7.68 (m, 3H), 7.57−7.42 (m,
5H), 7.28−7.19 (m, 2H), 7.11−7.09 (m, 1H) ppm. 13C{1H} NMR
(100 MHz, CDCl3): δ 145.6, 144.2, 134.3, 133.7, 133.6, 132.7, 132.1,
128.83, 128.76, 128.5, 128.4, 127.9, 127.6, 126.7, 126.3, 126.2, 125.5,
125.47, 124.7, 124.1 ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd
for C31H20N, 406.1590; found, 406.1599.
5,9-Dibromo-7-phenyldibenzo[c,h]acridine (6f). Brown liquid.
Yield: 339 mg (66%). Rf: 0.62 (EtOAc/hexane, 1:19 v/v). 1H
NMR (400 MHz, CDCl3): δ 9.46−9.42 (m, 1H), 9.09−9.06 (m, 1H),
8.19−7.76 (m, 3H), 7.62−7.57 (m, 4H), 7.52−7.30 (m, 6H) ppm.
13C{1H} NMR (100 MHz, CDCl3): δ 148.6, 147.9, 138.3, 137.7
133.4, 132.7, 131.8, 129.6, 128.9, 128.6, 128.0, 127.4, 126.6, 124.9,
123.0 ppm. MS (ESI) m/z: 533.37 [M + Na]+. Anal. Calcd for
C27H15Br2N: C, 63.19; H, 2.95; N, 2.73. Found: C, 63.43; H, 2.97; N,
2.69.
5,9-Dinitro-7-phenyldibenzo[c,h]acridine (6i). Pale yellow solid.
Yield: 232 mg (52%). Mp: 217−219 °C. Rf: 0.16 (EtOAc/hexane,
1
1:19 v/v). H NMR (400 MHz, CDCl3): 8.84 (d, J = 2.4 Hz, 2H),
8.55−8.43 (m, 2H), 8.33−8.25 (m, 6H), 8.09 (d, J = 8.4 Hz, 1H),
7.63−7.58 (m, 4H) ppm. 13C NMR (100 MHz, CDCl3): 160.7,
150.4, 145.2, 138.52, 138.46, 131.4, 130.5, 129.1, 127.9, 125.9, 124.4,
123.2, 120.7 ppm. MS (ESI) m/z: 481.26 [M + 2H2O]+. Anal. Calcd
for C27H15N3O4: C, 72.80; H, 3.39; N, 9.43. Found: C, 72.94; H,
3.44; N, 9.40.
(E)-7-Styryldibenzo[c,h]acridine (6j). Dark brown liquid. Yield:
267 mg (70%). [Yield: 756 mg (66%) on 3.0 mmol scale]. Rf: 0.80
1
(EtOAc/hexane, 1:19 v/v). H NMR (400 MHz, CDCl3): δ 9.50−
9.48 (m, 1H), 8.34−8.33 (m, 2H), 8.19−8.17 (m, 1H), 8.09−7.88
(m, 3H), 7.78−7.70 (m, 7H), 7.69−7.45 (m, 5H) ppm. 13C{1H}
NMR (100 MHz, CDCl3): δ 155.5, 146.3, 139.8, 136.6, 133.9, 131.9,
129.3, 128.9, 128.2, 127.9, 127.53, 127.50, 127.0, 125.21, 125.16,
124.8, 118.9 ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C29H20N, 382.1590; found, 382.1604.
(E)-7-(4-Methoxystyryl)dibenzo[c,h]acridine (6k). Brown liquid.
1
Yield: 247 mg (60%). Rf: 0.63 (EtOAc/hexane, 1:19 v/v). H NMR
(400 MHz, CDCl3): δ 9.44 (d, J = 8.0 Hz, 1H), 8.24 (d, J = 15.2 Hz,
1H), 7.88−7.50 (m, 8H), 7.40−7.33 (m, 5H), 7.31−7.21 (m, 3H),
4.33 (s, 3H) ppm. 13C{1H} NMR (100 MHz, CDCl3): δ 152.7, 144.9,
139.7, 137.1, 135.1, 133.7, 132.3, 128.9, 128.82, 128.77, 128.0, 127.9,
127.5, 126.7, 125.6, 125.1, 124.6, 38.6 ppm. HRMS (ESI-TOF) m/z:
[M + H]+ calcd for C30H22NO, 412.1696; found, 412.1692.
(E)-7-[2-(Thien-2-yl)vinyl]dibenzo[c,h]acridine (6l). Brown liquid.
1
Yield: 239 mg (62%). Rf: 0.53 (EtOAc/hexane, 1:19 v/v). H NMR
(400 MHz, CDCl3): δ 9.78 (d, J = 8.0 Hz, 1H), 7.84−7.65 (m, 6H),
7.41−7.35 (m, 4H), 7.28−7.21 (m, 4H), 6.68−6.66 (m, 2H) ppm.
13C{1H} NMR (100 MHz, CDCl3): δ 148.2, 147.2, 140.7, 139.3,
133.4, 131.7, 128.8, 128.5, 128.1, 127.9, 127.7, 127.4, 127.2, 125.0,
D
https://dx.doi.org/10.1021/acs.joc.0c02105
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
124.3, 122.8, 122.7 ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C27H18NS, 388.1154; found, 388.1153.
Author
Murugesan Thangamani − School of Chemistry,
Bharathidasan University, Tiruchirappalli, Tamil Nadu 620
024, India
(E)-5,9-Dibromo-7-styryldibenzo[c,h]acridine (6m). Dark brown
1
liquid. Yield: 323 mg (60%). Rf: 0.72 (EtOAc/hexane, 1:19 v/v). H
NMR (400 MHz, CDCl3): δ 9.70 (d, J = 8.0 Hz, 1H), 8.02−7.98 (m,
3H), 7.84−7.65 (m, 3H), 7.47−7.36 (m, 5H), 7.27−7.15 (m, 2H),
6.94−6.92 (m, 2H), 6.24 (s, 1H) ppm. 13C{1H} NMR (100 MHz,
CDCl3): δ 140.3, 134.7, 133.5, 132.5, 128.7, 128.5, 127.7, 127.2,
127.1, 126.9, 126.2, 126.1, 125.7, 125.6, 122.4, 121.8, 115.5 ppm.
HRMS (ESI-TOF) m/z: [M + NH4]+ calcd for C29H21Br2N2,
555.0066; found, 555.0059.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02105
Notes
The authors declare no competing financial interest.
(E)-5,9-Dibromo-7-[2-(naphthalen-2-yl)vinyl]dibenzo[c,h]-
acridine (6n). Dark brown liquid. Yield: 388 mg (66%). Rf: 0.56
(EtOAc/hexane, 1:19 v/v). 1H NMR (400 MHz, CDCl3): δ 9.43 (d, J
= 8.0 Hz, 2H), 9.04 (d, J = 4.4 Hz, 2H), 8.23−8.19 (m, 2H), 7.95−
7.76 (m, 6H), 7.61−7.57 (m, 4H), 7.43−7.27 (m, 3H) ppm. 13C{1H}
NMR (100 MHz, CDCl3): δ 151.0, 148.2, 147.3, 146.1, 140.7, 139.3,
136.4, 133.4, 131.7, 129.9, 128.9, 128.5, 128.1, 128.9, 127.9, 127.7,
127.3, 125.0, 122.8, 122.7, 117.5 ppm. MS (ESI) m/z: 588.41 [M +
H]+. Anal. Calcd for C33H19Br2N: C, 67.26; H, 3.25; N, 2.38. Found:
C, 67.40; H, 3.33; N, 2.29.
ACKNOWLEDGMENTS
■
The authors thank the Science and Engineering Research
Board (SERB), India, for financial support and DST-FIST for
instrumentation facilities at the School of Chemistry,
Bharathidasan University. M.T. thanks the University Grants
Commission (UGC) for a BSR-RFSMS fellowship.
REFERENCES
■
(E)-5,9-Dibromo-7-[2-(thiophen-2-yl)vinyl]dibenzo[c,h]acridine
(6o). Brown liquid. Yield: 327 mg (60%). Rf: 0.64 (EtOAc/hexane,
1:19 v/v). 1H NMR (400 MHz, CDCl3): δ 8.49 (s, 1H), 8.41 (d, J =
8.4 Hz, 2H), 8.29 (d, J = 8.4 Hz, 2H), 7.97−7.95 (m, 2H), 7.79−7.77
(m, 2H), 7.71−7.51 (m, 4H), 6.93−6.91 (m, 2H) ppm. 13C{1H}
NMR (100 MHz, CDCl3): δ 159.2, 148.7, 137.9, 134.7, 132.2, 130.2,
130.0, 129.9, 129.2, 129.0, 127.9, 127.1, 126.6, 124.5, 120.2, 113.1
ppm. MS (ESI) m/z: 542.31 [M]+. Anal. Calcd for C27H15Br2NS: C,
59.47; H, 2.77; N, 2.57. Found: C, 59.68; H, 2.81; N, 2.49.
(E)-5,9-Dinitro-7-styryldibenzo[c,h]acridine (6p). Yellow solid.
Yield: 287 mg (61%). Mp: 212−214 °C. Rf: 0.12 (EtOAc/hexane,
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1:19 v/v). H NMR (400 MHz, CDCl3): 9.04 (d, J = 8.4 Hz, 2H),
8.45 (d, J = 7.2 Hz, 2H), 8.05 (d, J = 8.4 Hz, 2H), 7.88 (d, J = 8.0 Hz,
2H), 7.62−7.43 (m, 6H), 7.29−7.26 (m, 6H) ppm. 13C NMR (100
MHz, CDCl3): 162.4, 155.2, 143.7, 132.5, 130.0, 129.5, 129.1, 128.9,
127.0, 126.1, 125.9, 124.9, 123.3, 111.2 ppm. MS (ESI) m/z: 504.34
[M + MeOH + H]+. Anal. Calcd for C29H17N3O4: C, 73.88; H, 3.63;
N, 8.91. Found: C, 73.96; H, 3.56; N, 8.80.
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02105.
Copies of 1H and 13C NMR spectra for all products 6a−
p and the ORTEP plot of the crystal structure of 6a
(PDF)
Accession Codes
CCDC 1988029 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK. Fax: +44-1223-336033.
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AUTHOR INFORMATION
■
Corresponding Author
Kannupal Srinivasan − School of Chemistry, Bharathidasan
University, Tiruchirappalli, Tamil Nadu 620 024, India;
orcid.org/0000-0001-5044-4716; Phone: +91-431-
2407053; Email: srinivasank@bdu.ac.in; Fax: +91-431-
2407043
E
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