Synthesis of novel fluoranthene-based conformationally constrained α-amino acid derivatives and polycyclic aromatics via the diels-alder reaction

Article abstract of DOI:10.1055/s-0033-1341042

Conformationally constrained cyclic α-amino acid moieties have been fused to the fluoranthene system. Aminoindanecarboxylic acid (Aic) and 1,2,3,4-tetrahydroisoquinolinecarboxylic acid (Tic) derivatives were synthesized by an alkylation sequence, whereas a aminotetralincarboxylic acid (Atc) derivative was assembled using the Diels-Alder reaction as a key step. These α-amino acid derivatives are considered as constrained analogues of phenylalanine (Phe) and play an important role in the design and synthesis of bioactive peptides and some fluorescence chemosensor molecules. Moreover, this strategy has been extended to polycyclic aromatics via the Diels-Alder reaction and subsequent aromatization with DDQ. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0033-1341042

PAPER
▌1525
paper
Synthesis of Novel Fluoranthene-Based Conformationally Constrained α-Amino
Acid Derivatives and Polycyclic Aromatics via the Diels–Alder Reaction
Novel Fluoranthene-Based α-Amino Acid Derivatives
Sambasivarao Kotha,* Milind Meshram
Department of Chemistry, Indian Institute of Technology-Bombay, Mumbai, 400076, India
Fax +91(22)25723480; E-mail: srk@chem.iitb.ac.in
Received: 02.01.2014; Accepted after revision: 25.02.2014
act as fluorescent chemosensors for the detection of ex-
Abstract: Conformationally constrained cyclic α-amino acid moi-
plosives such as 2,4,6-trinitrotoluene and picric acid.3d
eties have been fused to the fluoranthene system. Aminoindanecar-
boxylic acid (Aic) and 1,2,3,4-tetrahydroisoquinolinecarboxylic
acid (Tic) derivatives were synthesized by an alkylation sequence,
whereas a aminotetralincarboxylic acid (Atc) derivative was assem-
bled using the Diels–Alder reaction as a key step. These α-amino
acid derivatives are considered as constrained analogues of phenyl-
alanine (Phe) and play an important role in the design and synthesis
of bioactive peptides and some fluorescence chemosensor mole-
cules. Moreover, this strategy has been extended to polycyclic aro-
matics via the Diels–Alder reaction and subsequent aromatization
with DDQ.
In view of the interesting photophysical and electrochem-
ical properties of various fluoranthene-fused derivatives,
strategies for their syntheses are of great interest.2–4 To
this end, Fabrizio et al. reported the synthesis of fluoran-
thene-fused sulfone derivatives such as 9,10-dimethylsul-
fone-7,12-diphenylbenzo[k]fluoranthene 1 (DSDPBF)2
employing the Diels–Alder reaction. On the other hand,
Pei and co-workers reported the synthesis of fluoran-
thene-fused imide derivatives3b,c using the Diels–Alder re-
action and decarbonylation as key steps. Similarly, Patil
and co-workers demonstrated the synthesis of fluoran-
thene-fused derivatives, such as fluorescent chemosensor
6,3d by the Diels–Alder reaction.
Key words: amino acids, alkylation, bioorganic chemistry, fused-
ring systems, Diels–Alder reaction
Various polycyclic aromatic hydrocarbons (e.g., fluoran-
thene derivatives) play significant roles in optoelectron-
ics, fluorescent chemosensors, and self assembly. They
can act as critical building blocks in the design of organic
light-emitting diodes (OLEDs) and organic field-effect
transistors (OFETs).1 In this regard, fluoranthene-fused
sulfones such as 1 act as a light-emitting compound.2
Moreover, fluoranthene derivatives (Figure 1), such as 2
and 3,3a and 4 and 5,3b,c exhibit interesting photophysical
and electrochemical properties, and compounds such as 6
As a part of our major program for the design of unusual
α-amino acid derivatives and polycyclic aromatics, we
chose to incorporate the fluoranthene ring as a core struc-
tural unit and thus α-amino acid derivatives 7–9 and poly-
cyclic aromatics such as 10–12 became our synthetic
targets. Due to various interesting properties of fluoran-
thene-fused derivatives,2–4 we designed a simple route to
these α-amino acid derivatives and polycyclic compounds
using the Diels–Alder reaction5 and alkylation as key
steps. Here, we report a simple route to fluoranthene-
Ph
O
S
O
Ph
DSDPBF (1)
2
OC6H13
Ar
O
Ar
NC
3
N
R
NC
O
Ar
Ar
OC6H13
4 R = C8H17
5 R = C6F5
6
Figure 1 Various fluoranthene-fused polycyclic aromatic hydrocarbons2,3
SYNTHESIS 2014, 46, 1525–1531
Advanced online publication: 31.03.2014
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1341042; Art ID: SS-2014-Z0002-OP
© Georg Thieme Verlag Stuttgart · New York

1526
S. Kotha, M. Meshram
PAPER
NHAc
CO2Me
CO2Et
CO2Et
NHAc
CO2Et
N
Ac
7
8
9
CO2Me
CO2Me
O
O
S
S
O
O
10
11
12
Figure 2 Fluoranthene-fused α-amino acid derivatives 7–9 and polycyclic aromatics 10–12
fused conformationally constrained cyclic α-amino acid acetamidoacrylate (16) involving the transient diene inter-
derivatives involving aminoindanecarboxylic acid 7 mediate 10A. Our strategy may be extended toward the
(Aic), 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid 8 synthesis of fluoranthene-fused polycyclic compound 12
(Tic), and aminotetralincarboxylic acid 9 (Atc) deriva- by a Diels–Alder reaction involving sultine intermediate
tives, and polycyclic compounds such as 10–12 (Figure 10, which can act as a latent diene equivalent 10A
2).
(Scheme 1).
In the design of conformationally constrained α-amino The required 8,9-dimethylfluoranthene (17) was prepared
acid derivatives,6–13 fluoranthene-fused derivatives 7–9 by following the literature procedure.15,16 Although, Clar
and polycyclic aromatic compound 12 are considered and Stephen17a reported the synthesis of 8,9-bis(bromo-
worthwhile targets. To this end, 8,9-bis(bromometh- methyl)fluoranthene (13) by a different route17 with limit-
yl)fluoranthene (13) was identified as a key building ed data (melting point and CHN analysis only), we
block. A possible route to α-amino acid derivatives 7 and prepared 8,9-bis(bromomethyl)fluoranthene (13) by fol-
8 was envisioned involving ethyl isocyanoacetate (14)14 lowing a slightly modified route with the aid of N-bromo-
and diethyl acetamidomalonate (15). Alternatively, α- succinimide by adopting the radical bromination of an
amino acid derivative 9 could be derived by Diels–Alder aromatic methyl group.
reaction of fluoranthene-fused sultine 10 and methyl 2-
NHAc
CO2Me
CO2Et
CO2Et
NHAc
CO2Et
N
Ac
CO2Et
7
9
8
EtO2C
AcHN
CO2Me
EtO2C
NC
14
NHAc
15
16
Br
Br
O
S
O
17
13
10
CO2Me
CO2Me
12
10A
18
Scheme 1 Retrosynthetic pathway to α-amino acid derivatives and polycyclic aromatics
(i)
(ii)
(iii)
+
84%
2 steps
80%
18
19
20
21
17
Scheme 2 Preparation of 8,9-dimethylfluoranthene (17). Reagents and conditions: (i) DDQ, toluene, reflux, 24 h; (ii) toluene, sealed tube,
150 °C, 48 h; (iii) chloranil, o-xylene, reflux, 7 h.
Synthesis 2014, 46, 1525–1531
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Novel Fluoranthene-Based α-Amino Acid Derivatives
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HO
SO2Na
toluene, reflux
24
Br
Br
O
S
O
O
S
TBAB, DMF
0 °C, 4 h
25 h, 74%
O
13
10 89%
11
NHAc
toluene
reflux, 43 h
CO2Me
16
NHAc
CO2Me
9 50%
Scheme 3 Synthesis of tetralin-based α-amino acid 9 derivative via sultine building block 10
In this regard, we started from readily available 1,2-dihy- Treatment of 8,9-dimethylfluoranthene (17) with N-bro-
droacenaphthene (18), which was oxidized with 2,2-di- mosuccinimide in the presence of catalytic amounts of
chloro-5,6-dicyano-1,4-benzoquinone (DDQ) in toluene radical initiator such as benzoyl peroxide in various sol-
at reflux to give acenaphthylene (19) as a yellow crystal- vent systems under reflux conditions gave two products,
line solid in 80% yield, which was subjected to a [4+2]- dibromide 13 and ether 22, in low yields (entries 1–3). In
cycloaddition reaction with 2,3-dimethylbuta-1,3-diene an attempt to improve the yield, 8,9-dimethylfluoranthene
(20) (toluene, sealed tube, 150 °C, 48 h) to deliver the cy- (17) was treated with benzyltrimethylammonium
cloadduct 21. Treatment of the cycloadduct 21 with tribromide18 in the presence of benzoyl peroxide in di-
chloranil in refluxing o-xylene for seven hours gave 8,9- chloromethane–methanol (1:1) at 65 °C, but this gave
dimethylfluoranthene (17) as a pale-yellow crystalline ring-substituted product 23 in 84% yield (entry 4). The di-
solid in 84% yield (Scheme 2).
bromide 13 was obtained in 40% yield by treating com-
pound 17 with N-bromosuccinimide in carbon
tetrachloride in the presence of a catalytic amount of ben-
zoyl peroxide at room temperature for two hours by irra-
diation with a 200-W lamp (entry 6). The product was
purified by silica gel column chromatography. Elution of
the column with 10% dichloromethane in petroleum ether
gave the product and further crystallization from benzene
furnished the crystalline product. 8,9-Bis(bromometh-
Toward the synthesis of α-amino acid derivatives, such as
7–9, and polycyclic derivatives, the synthesis of the key
building block 8,9-bis(bromomethyl)fluoranthene (13)
seems to be a non-trivial task. In this regard, 8,9-dimeth-
ylfluoranthene (17) was subjected to radical bromination
to deliver 8,9-bis(bromomethyl)fluoranthene (13).17a The
results are summarized in Table 1.
1
yl)fluoranthene (13) was characterized by H and 13C
Table 1 Reaction Conditions for the Preparation of 8,9-Bis(bromomethyl)fluoranthene (13)
benzylic
bromination
Br
Br
O
+
+
Br
17
13
22
23
Entry
Reagent
Initiator
Solvent
Temp (°C)
Time (h)
Yielda (%)
13
22
23
1
2
3
4
5
6
NBS
Bz2O2
Bz2O2
Bz2O2
Bz2O2
AIBN
Bz2O2
CCl4
75–80
75–80
100
15
6
15
4
10
13
24
–
–
NBS
CCl4
–
NBS
PhCF3
4
10
–
–
BnMe3NBr3
NBS
CH2Cl2–MeOH (1:1)
65
3
84
–
CCl4
CCl4
75–80
r.t.b
51
2
12
40
15
–
NBS
–
a Yields refers isolated yields of various products as characterized by 1H and 13C NMR spectroscopic data.
b Conducted using hν (200 W lamp).
© Georg Thieme Verlag Stuttgart · New York
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S. Kotha, M. Meshram
PAPER
CO2Et
CO2Et
NHAc
CO2Et
(i)
(ii)
Br
Br
N
19%
(3 steps)
30%
Ac
7
13
8
Scheme 4 Synthesis of indane- and Tic-based α-amino acid derivatives. Reagents and conditions: (i) (a) ethyl isocyanoacetate (14),
Bu4NHSO4, K2CO3, MeCN, 75 °C, 21 h; (b) EtOH, concd HCl, CH2Cl2, r.t., 3 h; (c) Ac2O, MeCN, r.t., 42 h; (ii) diethyl acetamidomalonate
(15), K2CO3, MeCN, reflux, 15 h.
CO2Me
CO2Me
(i) toluene, reflux, 25 h
O
S
+
(ii) toluene, reflux, DDQ
19 h
O
CO2Me
CO2Me
10
12 32% (2 steps)
25
Scheme 5 Synthesis of polycyclic aromatic 12
NMR spectroscopic data and further supported by mass The steady state absorption spectra were recorded on a
spectral data where fragment ion corresponds to the [M – Jasco V530 spectrophotometer, and steady state PL spec-
Br] fragment.
tra were recorded on a Varian Cary Eclipse fluorescence
spectrophotometer bandwidth of 5 nm. Fluoranthene is
known to exhibit strong fluorescence owing to its rigid
and highly conjugated structure. The quantum yield (QY)
of fluoranthene is 0.30 in dilute cyclohexane solution.19
The fluoranthene-based α-amino acid derivatives were
studied, and are found to be considerably fluorescent. All
the fluorescence measurements were performed using dry
acetonitrile as the solvent. The fluorescent QY
calculated20 for the three derivatives were between 0.1 to
0.3. Furthermore, it has been shown that Tic derivative 2
has similar value of QY (0.28), indane- 1 and tetralin-
based 3 α-amino acid derivatives have QY (0.10) and
(0.14) respectively nearly half that compared to the fluor-
anthene chromophore. The time resolved fluorescent
measurements were performed using a time-correlated
single photon counting (TCSPC) system, from IBH (UK),
with λex = 294 nm. The fluorescence decay profile of the
compounds showed a fast fluorescence decay component
of around 500 ps in addition to a slow component. Due to
the different functional groups and various ring substitu-
ents in the fluoranthene unit, there is slight difference in
the fluorescence lifetime. The data for the fluorescence
study can be found in the supporting information.
The dibromo compound 13 was treated with sodium hy-
droxymethanesulfinate (rongalite) (24) in N,N-dimethyl-
formamide in the presence of tetrabutylammonium
bromide as a phase-transfer catalyst at 0 °C for four hours
to afford the sultine 10 in 89% yield. However, NMR data
indicate that the sultine product was contaminated with a
small amount of sulfone 11 and it was difficult to remove
the sulfone by column chromatography. Further, sultine
10 was heated at 100 °C to deliver the corresponding sul-
fone 11 in 74% yield. Later, the sultine 10 was treated
with methyl 2-acetamidoacrylate (16) in toluene at reflux
for 43 hours to furnish the desired product, aminotetralin-
carboxylic acid 9 (Atc) derivative in 50% yield (Scheme
3).
Next, the 8,9-bis(bromomethyl)fluoranthene (13) was re-
acted with ethyl isocyanoacetate (14) in the presence of
potassium carbonate in refluxing acetonitrile under phase-
transfer conditions to give the alkylated product, which
was directly treated with concentrated hydrochloric acid
in absolute ethanol to generate the desired amino ester.
Subsequent acetylation of the amino ester with acetic an-
hydride in acetonitrile at room temperature gave the de-
sired acetylated product 7 as an off-white solid in 19%
yield (3 steps; overall yield). Similarly, the dibromide 13
reacted with diethyl acetamidomalonate (15) in the pres-
ence of potassium carbonate as the base in acetonitrile at
reflux for 15 hours to furnish the required 1,2,3,4-tetrahy-
droisoquinoline-3-carboxylic acid (Tic) 8 derivative as a
white solid in 30% yield (Scheme 4).
We have demonstrated a simple strategy for the synthesis
of novel fluoranthene-fused conformationally constrained
cyclic α-amino acid derivatives via the Diels–Alder reac-
tion as a key step. This strategy has been extended to poly-
cyclic aromatics. Moreover, the methodology developed
here is useful for the design the biologically active com-
pounds and is likely to play a significant role in the prep-
aration of optoelectronics and fluorescent chemosensors
molecules.
To expand this strategy to fluoranthene-fused polycyclic
aromatics, sultine derivative 10 was treated with dimethyl
acetylenedicarboxylate (25) in refluxing toluene for 25
hours to afford the cycloadduct, which was directly sub-
jected to an aromatization sequence in the presence of
DDQ in refluxing toluene to give the desired aromatized
product 12 in 32% (Scheme 5).
Melting points were recorded on a Labhosp or Veego melting point
apparatus and are uncorrected. 1H NMR spectra were generally re-
corded on Varian VXR (400 MHz) or Bruker (400 MHz) spectrom-
eters. 13C NMR spectra were recorded on Varian VXR (75 MHz) or
Bruker (100 MHz) spectrometers. NMR spectra were generally per-
Synthesis 2014, 46, 1525–1531
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Novel Fluoranthene-Based α-Amino Acid Derivatives
1529
formed in CDCl3 soln with TMS as the internal standard. Analytical
TLC was performed on glass plates coated with silica gel G or GF
254 (Acme, 13% CaSO4 as a binder).
3-Bromo-8,9-dimethylfluoranthene (23) (Table 1, Entry 4)
To a 50-mL round-bottomed flask were added 8,9-dimethylfluoran-
thene (17, 30 mg, 0.13 mmol) and Bz2O2 (15 mg, 0.5 equiv) in
CH2Cl2–MeOH (1:1, 15 mL). Then BnMe3NBr3 (146 mg, 0.39
mmol) was added, and the mixture was refluxed under N2 for 3 h
(TLC monitoring). The mixture was extracted with CH2Cl2 (2 × 15
mL). The organic layer was washed with H2O (2 × 15 mL), dried
(anhyd Na2SO4), and filtered. Evaporation of the solvent gave the
crude product, which was purified by column chromatography
(10% EtOAc–PE) to afford 23 (33.9 mg, 84%) as a pale-yellow sol-
id; mp 165–167 °C.
All reactions were monitored by TLC using an appropriate solvent
system for development. The transfer of moisture-sensitive materi-
als was carried out using standard syringe-septum techniques and
reactions were maintained under a N2 atmosphere until workup. An-
hyd CCl4 and CH2Cl2 were obtained by distillation over P2O5.
MgSO4 and Na2SO4 were dried in an oven at 130 °C for 1 d. All sol-
vent extracts were washed successively with H2O and brine, dried
(anhyd MgSO4 or Na2SO4), and concentrated at reduced pressure on
a Buchi R-114 rotary evaporator. Petroleum ether = PE. Yields re-
ported are isolated, chromatographically pure, yields. Ethyl isocya-
noacetate was prepared by following the literature procedure.14
Methyl 2-acetamidoacrylate and diethyl acetamidomalonate were
purchased from Aldrich. All the commercial grade reagents were
used without further purification.
IR (neat): 3054, 2987, 1559, 1422, 1362, 1052, 739 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.93 (d, J = 8.4 Hz, 1 H, HAr), 7.83
(d, J = 6.7 Hz, 1 H, HAr), 7.77 (d, J = 7.6 Hz, 1 H, HAr), 7.65–7.59
(m, 4 H, HAr), 2.37 (s, 6 H, 2 CH3).
13C NMR (100 MHz, CDCl3): δ = 137.8, 137.3, 137.2, 136.8, 136.5,
133.9, 131.2, 130.0, 129.2, 125.5, 123.1, 123.0, 121.3, 120.2, 120.2,
20.5, 20.5.
8,9-Bis(bromomethyl)fluoranthene (13)17a (Table 1, Entry 6)
To a 50-mL round-bottomed flask was added 8,9-dimethylfluoran-
thene (17, 200 mg, 0.09 mmol) in CCl4 (15 mL). Then, NBS (321
mg, 1.80 mmol) and Bz2O2 (0.25 equiv) were added. The resulting
mixture was stirred at r.t. under irradiation (200-W lamp) for 2 h
(TLC monitoring). At the conclusion of the reaction, the mixture
was extracted with CH2Cl2 (2 × 15 mL). The organic layer was
washed with H2O (2 × 15 mL), dried (anhyd Na2SO4), and filtered.
Evaporation of the solvent gave the crude product, which was puri-
fied by column chromatography (10% CH2Cl2–PE) to afford 13
(136.5 mg, 40%) as a pale-yellow solid, which on further crystalli-
zation (benzene) afforded needle-shaped crystals; mp 195–196 °C.
(Note: Since, benzene is known to be carcinogenic, extra care
should be taken while handling benzene and the experiment was
carried out in well-ventilated hood.)
HRMS (Q-ToF MS ES+): m/z [M + H]+ calcd for C18H14Br:
309.0276; found: 309.0279.
1,4-Dihydrofluorantheno[8,9-d][1,2]oxathiin-3-one (10)
To a suspension of rongalite 24 (240 mg, 1.5 mmol) in DMF (4 mL)
was added 13 (60 mg, 0.15 mmol) and TBAB (48 mg, 0.15 mmol).
The resulting suspension was stirred at 0 °C for 4 h (TLC monitor-
ing). The mixture was diluted with H2O (10 mL) and extracted with
CH2Cl2. The organic layer was washed with H2O (2 × 10 mL) and
dried (anhyd Na2SO4). Evaporation of the organic layer under re-
duced pressure gave crude product, which was purified by column
chromatography (20% EtOAc–PE) to afford 10 (40.8 mg, 89%) as
an off-white solid; mp 267–268 °C.
IR (neat): 2983, 2934, 1508, 1353, 1275, 1053, 747 cm–1.
IR (neat): 3054, 2987, 1559, 1422, 1351, 1047, 740 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.90 (m, 4 H, HAr), 7.72 (s, 2 H,
HAr), 7.69 (m, 2 H, HAr), 5.38 (0.5 ABq, J = 3.5 Hz, 1 H), 5.06 (0.5
ABq, J = 3.4 Hz, 1 H), 4.56 (0.5 ABq, J = 15.3 Hz, 1 H), 3.65 (0.5
ABq, J = 15.2 Hz, 1 H).
1H NMR (400 MHz, CDCl3): δ = 7.94 (d, J = 6.7 Hz, 2 H, HAr), 7.88
(s, 2 H, HAr), 7.86 (s, 2 H, HAr), 7.66–7.62 (m, 2 H, HAr), 4.81 (s, 4
H, 2 CH2Br).
13C NMR (100 MHz, CDCl3): δ = 140.5, 135.8, 133.0, 130.1, 128.2,
127.6, 124.3, 121.0, 31.1.
HRMS (Q-ToF MS ES+): m/z [M – Br] calcd for C18H12Br:
307.0.121; found: 307.0122.
13C NMR (100 MHz, CDCl3): δ = 139.9, 139.2, 136.0, 133.6, 132.7,
130.1, 128.2, 128.2, 127.5, 127.3, 125.9, 122.6, 120.7, 120.6, 119.2,
119.0, 64.4, 58.6.
HRMS (Q-ToF MS ES+): m/z [M + H]+ calcd for C18H13O2S:
293.0636; found: 293.0629.
8,9-Bis(bromomethyl)fluoranthene (13) and 1,3-Dihydroace-
naphtho[1,2-f]isobenzofuran (22) (Table 1, Entry 1)
1,3-Dihydroacenaphtho[1,2-f]isobenzothiophene-2,2-dione (11)
To a 25-mL round-bottomed flask was added sultine 10 (15 mg) in
toluene (3 mL) the mixture was heated at 100 °C for 25 h (TLC
monitoring). Evaporation of the solvent gave the crude product,
which was further purified by column chromatography (20%
EtOAc–PE) to afford 11 (11 mg, 74%) as a yellow solid; mp 272–
274 °C.
To a 50-mL round-bottomed flask was added 8,9-dimethylfluoran-
thene (17, 60 mg, 0.26 mmol) in CCl4 (12 mL). Then, NBS (98 mg,
0.54 mmol) and Bz2O2 (31 mg, 0.5 equiv) were added. The resulting
mixture was stirred at 75 °C for 15 h (TLC monitoring). At the con-
clusion of the reaction, the mixture was extracted with CH2Cl2 (2 ×
15 mL). The organic layer was washed with H2O (2 × 15 mL), dried
(anhyd MgSO4), and filtered. Evaporation of the solvent gave the
crude product, which was purified by column chromatography
(10% EtOAc–PE) to afford dibromide 13 (15 mg, 15%) as a pale-
yellow solid and the ether 22 (6 mg, 10%) as an off-white solid.
IR (neat): 2989, 2928, 1542, 1418, 1296, 1119, 741 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.90–7.89 (m, 4 H, HAr), 7.77 (br
s, 2 H, HAr), 7.68 (m, 2 H, HAr), 4.48 (s, 4 H, ArCH2).
13C NMR (100 MHz, CDCl3): δ = 140.1, 135.8, 130.1, 130.1, 128.3,
127.6, 120.8, 119.1, 57.4.
Ether 22
Mp 222–224 °C.
IR (neat): 2956, 2917, 1559, 1454, 1421, 1041, 772 cm–1.
HRMS (ESI): m/z [M + Na] calcd for C18H12O2SNa: 315.0458;
found: 315.0450.
1H NMR (400 MHz, CDCl3): δ = 7.90 (d, J = 6.7 Hz, 2 H, HAr), 7.84
(d, J = 8.3 Hz, 2 H, HAr), 7.71 (s, 2 H, HAr), 7.64 (s, J = 8.0 Hz, 2 H,
HAr), 5.20 (s, 4 H, 2 CH2O).
Methyl 9-Acetamido-8,9,10,11-tetrahydrobenzo[k]fluoran-
thene-9-carboxylate (9)
To a solution of 10 (10 mg, 0.03 mmol) in toluene (3 mL) was added
methyl 2-acetamidoacrylate (16, 11 mg, 0.07 mmol). The resulting
mixture was refluxed for 43 h (TLC monitoring). Evaporation of the
solvent gave the crude product, which was further purified by col-
umn chromatography (50% EtOAc–PE) to afford 9 (6 mg, 50%) as
a white solid; mp 243–245 °C.
13C NMR (100 MHz, CDCl3): δ = 139.6, 138.8, 136.6, 132.9, 130.1,
128.1, 126.8, 120.0, 114.2, 73.7.
HRMS (Q-ToF MS ES+): m/z [M + H]+ calcd for C18H13O:
245.0966; found: 245.0962.
© Georg Thieme Verlag Stuttgart · New York
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S. Kotha, M. Meshram
PAPER
Dimethyl Benzo[k]fluoranthene-9,10-dicarboxylate (12)
IR (neat): 3053, 2987, 1724, 1541, 1422, 1049, 739 cm–1.
To a solution of 10 (37 mg, 0.12 mmol) in anhyd toluene (6 mL) was
added DMAD (25, 0.06 mL, 0.51 mmol); the mixture was refluxed
for 25 h under N2. At the conclusion of the reaction (TLC monitor-
ing), the solvent was removed at reduced pressure to deliver the
crude product, which was directly subjected to the aromatization re-
action without further purification.
1H NMR (400 MHz, CDCl3): δ = 7.90–7.87 (m, 2 H, HAr), 7.84 (s,
1 H, HAr), 7.82 (s, 1 H, HAr), 7.66–7.60 (m, 4 H, HAr), 5.73 (br s, 1
H, NH), 3.80 (s, 3 H, OCH3), 3.42 (d, J = 6.7 Hz, 1 H), 3.16 and 3.12
(d, J = 6.7, 6.8 Hz, 1 H), 3.06–2.88 (m, 2 H, CH2), 2.67–2.61 (m, 1
H, CH), 2.29–2.20 (m, 1 H, CH), 1.95 (s, 3 H, COCH3).
13C NMR (100 MHz, CDCl3): δ = 174.1, 170.3, 138.4, 138.0, 136.8,
136.8, 134.6, 133.0, 131.4, 130.2, 128.1, 126.7, 126.7, 122.6, 122.0,
119.9, 119.8, 58.2, 52.8, 38.7, 28.2, 26.0, 23.3.
To a solution of the crude Diels–Alder adduct in toluene (10 mL)
was added DDQ (1.2 equiv), and the mixture was refluxed for 19 h.
At the conclusion of the reaction (TLC monitoring), the mixture
was quenched with H2O and extracted with CH2Cl2 (3 × 10 mL).
The organic layer was washed with H2O, and dried (anhyd Na2SO4),
filtered. Evaporation of the solvent under reduced pressure gave the
crude product, which was purified by column chromatography (sil-
ica gel, 10% EtOAc–PE) to give 12 (32 mg, 32% over 2 steps) as a
pale-yellow solid; mp 151–153 °C.
HRMS (Q-ToF MS ES+): m/z [M + H]+ calcd for C24H22NO3:
372.1600; found: 372.1596.
Ethyl 9-Acetamido-9,10-dihydro-8H-cyclopenta[k]fluoran-
thene-9-carboxylate (7)
To a suspension of 13 (84 mg, 0.21 mmol), Bu4NHSO4 (28 mg, 0.08
mmol), and K2CO3 (580 mg, 4.2 mmol) in MeCN (15 mL) was add-
ed ethyl isocyanoacetate (14, 10 equiv). The mixture was stirred un-
der N2 at 75–80 °C for 21 h, then cooled to r.t., and filtered through
sintered glass. The solid obtained was washed with CH2Cl2 and the
filtrate was evaporated under reduced pressure. The crude product
obtained was hydrolyzed directly without further purification. The
crude product in CH2Cl2 (10 mL), was reacted with dry EtOH (20
mL) in the presence of concd HCl (1 mL). The mixture was stirred
at r.t. for 3 h and then diluted with CH2Cl2 (100 mL) and H2O (150
mL), and the mixture was made alkaline by slow addition of
NaHCO3 with stirring. The separated CH2Cl2 layer was washed
with H2O (2 × 30 mL), dried (anhyd Na2SO4), and then filtered.
Evaporation of the solvent gave the crude product, which was acet-
ylated directly. The crude product obtained was reacted in anhyd
MeCN (10 mL) with Ac2O (1.5 mL) at r.t. for 42 h. Evaporation of
the solvent gave the crude product, which was purified by column
chromatography (50% EtOAc–PE) to give pure 7 (15 mg, 19% over
3 steps) as an off-white solid; mp 225–227 °C.
IR (neat): 3055, 2986, 1723, 1446, 1127, 1053, 739 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.37 (s, 2 H, HAr), 8.34 (s, 2 H,
HAr), 8.09 (d, J = 6.9 Hz, 2 H, HAr), 7.93 (d, J = 8.0 Hz, 2 H, HAr),
7.73 (dd, J1 = 7.0 Hz, J2 = 7.0 Hz, 2 H), 3.99 (s, 6 H, 2 OCH3).
13C NMR (100 MHz, CDCl3): δ = 168.4, 140.5, 136.0, 135.4, 133.6,
130.8, 130.6, 128.5, 127.3, 120.8, 120.3, 52.9.
HRMS (Q-ToF MS ES+): m/z [M + H]+ calcd for C24H17O4:
369.1113; found: 369.1127.
Acknowledgement
We thank Department of Science and Technology (DST) and CSIR,
New Delhi for the financial support. S.K. thanks DST for the award
of a J. C. Bose fellowship. Milind Meshram thanks CSIR for the
award of a research fellowship. We also thank to Prof. Anindya Dat-
ta, and Mr. Avinash Singh for their help in collecting fluorescence
data.
IR (neat): 3274, 2988, 2944, 1688, 1574, 1420, 1362, 1047, 742 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.89 (d, J = 6.7 Hz, 2 H, HAr), 7.83
(d, J = 8.0 Hz, 2 H, HAr), 7.72 (s, 2 H, HAr), 7.63 (t, J = 6.7 Hz, 2 H,
HAr), 6.1 (s, NH), 4.27 (q, J = 7.2 Hz, 2 H, OCH2CH3), 3.76 and 3.36
(d, J = 16.3 Hz, 2 H, ArCH2 and d, J = 16.6 Hz, 2 H, ArCH2), 1.96
(s, 3 H, COCH3), 1.29 (t, J = 7.2 Hz, 3 H, OCH2CH3).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
m
tgioSrantnugIifoop
r
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13C NMR (100 MHz, CDCl3): δ = 173.0, 170.3, 139.5, 139.2, 136.9,
132.7, 130.1, 128.1, 126.6, 119.9, 118.0, 66.4, 61.9, 43.6, 23.3,
14.3.
HRMS (Q-ToF MS ES+): m/z [M + H]+ calcd for C24H22NO3:
372.1611; found: 372.1600.
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