Single step incorporation of carboxylic acid groups in the lower rim of calix[4]arenes: A recyclable catalyst towards assembly of diverse five ring fused acridines

Article abstract of DOI:10.1039/c5gc00156k

This is the first report of an efficient protocol for the incorporation of the -COOH moiety in a single step at the lower rim of calixarene to produce a new calix[4]arene grafted tricarboxylic acid, calix 4a. Generation of this catalyst was confirmed by NMR and HRMS analyses. The efficacy of this compound as an organocatalyst was successfully extended towards the synthesis of an assembly of new diversely substituted five ring fused acridine derivatives.

Full text of DOI:10.1039/c5gc00156k

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DOI: 10.1039/C5GC00156K
Journal Name
ARTICLE TYPE
First single step incorporation of carboxylic acid groups in the lower rim
of calix[4]arenes: a new recyclable catalyst towards assembly of diverse
five ring fused acridines
Piyali Sarkara and Chhanda Mukhopadhyay*a
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
5
45 challenge for their multi-step tedious synthetic procedure.
This is the first report of an efficient protocol of
incorporation of the –COOH moiety in a single step at the
lower rim of calixarene to produce a new calix[4]arene
10 grafted tricarboxylic acid, calix 4a. Generation of this catalyst
was confirmed by NMR and HRMS analyses. The efficacy of
this compound as an organocatalyst was successfully
extended towards the synthesis of an assembly of new
diversely substituted five ring fused acridine derivatives.
Previously reported upper rim substitution procedure contained
at least three steps, (i) removal of tertiary-butyl group, (ii)
protection of phenolic –OH group, and (iii) insertion of carbonyl
or carboxyl group in order to incorporate acid functionality.5 On
50 the other hand, all the reported examples of acid group
incorporation to the lower rim engaged protocols operating via
protection-deprotection steps.6 So, all those steps resulted in
lowering of the reaction efficiency. Having secured a facile one
step route to functionalize the lower rim with acid group, we tried
55 to focus on the controlling factors of direct substitution of
haloalkanes in the phenolic-OH group. It is our belief that an
increased organization of those factors will assist in the rational
extension of known methodology to allow incorporation of
unprotected –COOH group in a single step. Interestingly,
60 modification to temperature dependency and slow addition
technology brought us success to gain 90% yield of acid
substituted calixarene via a remarkably simple single step
protocol using sodium hydride in DMF.
15 Introduction:
A catalyst lies at the heart of enormous organic reactions as it
plays a crucial role to enforce the syntheses of many complex
organic compounds.1 In the recent decade, applicability of a
catalyst has been judged from the point of recyclability along
20 with its efficiency to reduce the environmental effect of catalytic
chemical technology. If we try to focus on the greenness of an
acid catalyst, avoiding usual organic (like acetic acid, butyric acid
etc.) and inorganic (like H2SO4, HCl etc.) acids, solid supported
or supramolecule supported acids get more impact.2 Solid
25 supported heterogeneous catalysts are of considerable interest in
recent years, but in contrast to recyclable behaviour, low
solubility is a drawback for many organic reactions. Thus, in
recent times, the significance of macromolecular homogeneous
organocatalysts has increased rapidly in synthetic organic
30 chemistry.3
Now, utilizing the catalytic activity of the newly generated
65 calixarene acid derivative, we thought to design a new method to
synthesize a new biologically important polynuclear heterocyclic
core. Polycyclic heteroaromatic alkaloids with 16-18 pi-electron
containing cores are of great importance due to their various
biological activities.7 Multi-ring fused acridine systems are such
70 type of alkaloids with high inhibition power to tumoral, fungal
and bacterial activities.8 Alpkinidines (1), cyclodercitine (2, 3)
etc. are marine sponge derived alkaloids having significant effect
regarding DNA intercalation and Topoisomerase I and II
inhibition.8,9
Calixarene grafted catalysts offer us the opportunity to improve
the green aspect of many reactions.4 Alignment of lipophilic and
lipophobic groups establish them as highly efficient
supramolecular organocatalysts in various organic protocols in
35 gripping organic as well as aqueous mediums.4 Their notable
stability towards many organic and inorganic substances enable
them to show reusable catalytic activities. In addition, their
stability towards moisture and air keep them away from
inconvenient air perceptive techniques. Considering these
40 enormous perspectives, functionalized calixarenes have been
widely used as organocatalysts for many organic syntheses since
the last decade.4 Strategic introduction of acid-functional
substituents at upper and lower rim of calixarene core is very
important, though the preparations of these are still a great
H3C
O
H3C
S
H3C
S
N
N
N
HO
O
N
N
N
N
N
N
H3C
1
2
3
75
Figure 1
For instance, as illustrated in Figure 1, several alkaloids having
This journal is © The Royal Society of Chemistry [year]
[journal], [year], [vol], 00–00 | 1

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DOI: 10.1039/C5GC00156K
ring fused acridine skeletons were reported to exhibit different 50 unreacted p-tert-butylcalix[4]arene after 4 h in reaction mixture
biological activities with therapeutic potential depending on the
substitution patterns of the core structure. Only a single step
towards this synthesis has been reported in literature.10 Therefore,
development of new strategy to install diverse functional groups
as the peak of –OH of the starting p-tert-butylcalix[4]arene is
totally absent in the crude NMR, i.e., 100% conversion occurred.
One more vital evidence in support of 100% conversion was
reflected from the HRMS data of the same crude product
5
at different positions of this core is still needed to extend 55 obtained from the reaction between p-tert-butylcalix[4]arene and
versatility of this scaffold in various medicinal applications. In
order to access a range of newly functionalized cores, we tried to
push calixarene chemistry to the forefront of the synthesis of that
2-bromopropionic acid (Figure 4). No trace of peak around
m/z=648.4179 convincingly proved the absence of the starting
material p-tert-butylcalix[4]arene. Additionally generation of
only the tri O-alkylated C4a can be confirmed from this
10 core in a one pot atom economic multi-component fashion. In this
context, our continuous effort enlightened an easy proficient 60 spectrum. The single configuration of the calixarene C4a was
protocol to produce a new series of five ring fused acridine
derivatives with a variety of substitutions in excellent yields via
reaction of equimolar (1 mmol of each) isatin, 5,5-dimethyl-1,3-
15 cyclohexanedione, aromatic or aliphatic amines with a slight
further confirmed by taking 1H-NMR of the pure C4a and
secondly C4a with little amount of fixatives (NaI and CD3CN)
(Figure 3).11 Interestingly addition of 0.005 mmol (0.75 mg) NaI
and 0.04 ml CD3CN to 0.5 ml 10 mM of C4a in CDCl3 we got a
excess (1.2 mmol) of acetylene dicarboxylate ester in presence of 65 simplified spectrum. For C4a, peak of tertiary butyl group (peak
catalytic amount (10 mol%) catalyst calixarene C4a in
dimethylformamide solvent. The synthetic route is convergent
and permits uncomplicated residency of substituent around the
d, Figure 3) produces a multiplet signal which simplifies after
addition of the fixatives. So, here fixation of only one i.e., cone
conformer occurs in CDCl3 solution confirming the presence of
the only one single isomer of C4a. The structure of the C4a was
70 established from 1H-NMR, 13C-NMR and HRMS.
20 core.
Result and Discussion:
Subsequently, to confirm the number of O-substitution, reactions
of different ω-bromoalkylacids such as bromoacetic acid and 5-
bromovaleric acid with p-tert-butylcalix[4]arene were performed
(Scheme 2). In case of bromoacetic acid we got the tetra O-
75 substituted product C4b as the only product. Any mono, di or tri
At the onset, we enlisted the bases that catalysed the o-
alkylation of calixarene to synthesize calixarene C4a. We
investigated with the usual weak bases K2CO3, Cs2CO3, etc. in
25 high efficient solvents (pyridine, DMF etc.) that resulted in poor
yield (upto 25%) at room temperature (25-30 ºC) rather than at
80-100 ºC. Also, the Arrhenius bases [NaOH, KOH, Ba(OH)2,
etc.] were ineffective to synthesize the desired acid substituted
calixarene.
Stacking diagram
Br
NaH, dry DMF
H2C COOH
20-25 ºC, 4h stirring
O
O
O
H
O
O
H
H
O
O
H
H
O
H3C
CH3
H3C
COOH
COOH
COOH
p-tert-butylcalix[4]arene
C4a
30
Scheme 1: Single step synthesis of C4a
This goal was achieved by stirring of p-tert-butylcalix[4]arene
(0.3 mmol) with 2-bromopropionic acid (3.33 mmol) in presence
35 of NaH (5 mmol) in 5 ml dry DMF (Scheme 1). The temperature
dependency of this methodology was shown in Table 1. Any
increase or decrease in reaction temperature from 20-25 ºC
notably hampered the reaction. So, the ideal reaction was
achieved at 20-25 ºC with a slow addition of the starting acid.
Figure 2: Study of conversion of p-tert-butylcalix[4]arene to C4a
40 The crude product was taken for NMR after completion of 4 h of
the reaction followed by quenching and washing with water. As
the excess unreacted 2-bomopropionic acid washed out with
water, we got only the three O-substituted acid C4a with a little
bit of impurity as the crude product. This implies that, under this
45 condition, the substitution selectivity was very high as no other
mono, di or tetra O-alkylated product were formed with tri O-
alkylated C4a. This was confirmed from comparison of crude
NMR for formation of C4a with the pure product presented in
Figure 2. The crude NMR also signifies nonexistence of any
80

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DOI: 10.1039/C5GC00156K
Figure 3: Study of conversion of calix[4]arene to C4a
phenomenon.
Our next target was to test the viability of our approach to
25 synthesize five ring fused acridine derivatives using C4a.
Initially, a screening was conducted to determine the optimal
conditions considering a representative reaction between 5,5-
Table 2: Optimization for the synthesis of C4a with respect to the
amount of the starting acida:
Entry Amount of 2-BPA
Added (eqiv.)
Amountb of unreacted p-tert- Yieldb (%)
butylcalix[4]arene (%)
1
2
3
4
5
6
4
6
8
10
11.1
12
80
52
20
8
0
0
12
39
72
83
92
92
Figure 4: High Resolution Mass Spectrum of the crude product of C4a
5 Table 1: Optimization for the synthesis of C4a
30 aReaction conditions: p-tert-butylcalix[4]arene (0.3 mmol) with 2-
bromopropionic acid (as mentioned) in presence of NaH (5 mmol) in 5 ml
dry DMF was stirred at 20-25 ºC for 4h. bIsolated.
Entry
2-BPA addition (1 drop Temperature
Yield (%)
per 5 second)
(ºC)
1
2
3
4
5
6
7
acid
acid
acid
100
21
32
42
72
92
76
55
dimethyl-1,3-cyclohexaedione (1 mmol), p-toluidine (1 mmol),
35 isatin (1 mmol) and dimethylacetylenedicarboxylate (1.3 mmol)
with variation of reaction parameters, such as catalyst, solvent,
reaction temperature etc., and the results are summarized in Table
3. Screening of the reaction conditions established that the nature
of the catalyst and the temperature of the reaction medium had a
40 significant effect on the yield of the product.
75-80
55-60
30-35
20-25
15-20
10-15
37.5% acid in DMF
37.5% acid in DMF
37.5% acid in DMF
37.5% acid in DMF
With our focus on recyclability and easy work up procedure, we
started searching the activity of well known organic acid
catalysts, p-toluenesulphonic acid, benzoic acid etc., and found
that their capability was much to low to produce the five ring
45 fused acridine derivative (9a). Subsequently, we scrutinized the
reaction with the aid of heterogeneous spherical mesoporous
silica nanoparticle supported carboxylic acid (SMSNP-CA,
Figure 5) and porous silica nanoparticle supported carboxylic
acid (PSNP-CA, Figure 5) under the same reaction conditions.
50 Although those acids performed a bit in water but the yields in
water were not appreciable. After suffering a setback with
heterogeneous catalyst, we turned our attention toward
organocatalysis again. Capability of some dicarboxylic acids was
screened but they furnished the expected product 9a only in poor
55 yields (entry 3-7). Further increment of one –COOH group was
also unsuccessful to catalyze this multicomponent reaction
efficiently (entry 8-10). To our delight one promising condition
was identified using newly synthesized catalyst C4a. Thus the
best yield, smooth reaction and easy work-up were achieved
NaH, dry DMF
(a)
Br
COOH
20-25 ºC, 4h stirring
O
O
O
O
H
H
O
H
H
O
O
O
COOH
COOH
COOH
COOH
p-tert-butylcalix[4]arene
C4b
Br
NaH, dry DMF
(b)
COOH
20-25 ºC, 4h stirring
O
O
O
H
O
H
H
O
H
H
O
O
O
H
H
HOOC
C4c
p-tert-butylcalix[4]arene
Scheme 2: Reaction of p-tert-butylcalix[4]arene with (a) bromoacetic
acid (b) 5-bromovaleric acid
10
O-alkylated products were not found. On the other hand, when
the number of carbon increases to five that is for 5-bromovaleric
acid, mono O-substituted C4c was formed as the single product. 60 employing 1.0 equiv. of each of dimedone (1 mmol), isatin (1
So, the selectivity of O-substituted product of p-tert-
mmol), and p-toluidine (1 mmol) with
15 butylcalix[4]arene depends on the bulk of the used acids
exhibiting steric-controlled phenomenon. The structure of the
C4b and C4b were established from 1H-NMR, 13C-NMR and
HRMS.
dimethylacetylenedicarboxylate (1.3 mmol) occupying 0.05
mol% of calixarene supported –COOH (C4a) as the exact picking
of catalyst and was established to be the key to obtain good to
65 excellent yields of the fused acridines (entry 16).
The nature of substitution does not depend on the amount of the
20 starting acid added. In all cases, as described in Table 2, only the
trisubstituted C4a has been formed to different extent. This result
also supports the steric-controlled single product formation
Further, to emphasize the importance of the present catalyst, we
studied a comparison of citric and isocitric acid with the C4a.
Although the former acids have the same functional groups, three
–COOH (Figure 5), with the later C4a but they triggered poor

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DOI: 10.1039/C5GC00156K
Entry
Catalyst
Solvent
Temp. Time (h) Yieldb (%)
(ºC)
yields of the expected product 9a in expense of longer reaction
times (entry 8-10). Again when the monomer of the calixarene
C4a (MC4a) (Figure 5) was used as catalyst no product was
formed (entry 12). So, the obtained results proved the
requirement of the cavity of the C4a to provide an affordable
environment for this reaction. Probably the aromatic groups of
the C4a provide stability towards the starting materials that
reflects the increase in yield along with the reaction rate at the
same time. We tried to find out the consequence of only the
10 cavity with very mild acidity i.e., p-tert-butylcalix[4]arene, that
resulted in failure to produce any product. But with increasing
incorporation of acid substitution i.e., from mono (C4c) to
triacidsubstituted calixarene (C4a), a continuous increase in yield
was definitely found (entries 13-16). Decisively, both the cavity
15 as well as the acidic substituents play simultaneous important role
in this reaction. On the other hand, further enhancement of acid
substitution i.e., use of the tetrasubstituted calixarene (C4b) did
not show any mentionable increase in yield which established the
C4a as the acceptable optimised catalyst. So, it can be concluded
20 that a minimum of three COOH groups at the lower rim of this p-
tert-butylcalix[4]arene are absolutely necessary, since four
COOH groups also catalyse the reaction with equal efficiency.
1
2
3
4
5
6
7
8
SMSNP-CA
PSNP-CA
Oxalic acid
Malonic acid
Succinic acid
Fumaric acid
Maleic acid
Propane-1,2,3-
trycarboxylic acid
Citric acid
Isocitric acid
Calix[4]arene
MC4a
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
100
100
100
100
100
100
100
100
72
72
72
72
72
72
72
72
18
15
35
27
25
28
27
36
5
9
H2O
H2O
100
100
100
100
100
100
80
100
100
120
100
100
100
100
100
72
72
72
72
72
72
72
12
18
12
72
72
72
72
72
38
38
NF
NF
12
33
NF
76
76
75
30
NF
NF
22
75
10
11
12
13
14
15
16
17
18
19
20
21
22
23
PEG+H2Oc
PEG+H2Oc
PEG+H2Oc
PEG+H2Oc
PEG+H2Oc
PEG+H2Oc
PEG+H2Oc
PEG+H2Oc
H2O
C4c
C4d
C4a
C4a
C4a
C4a
C4a
C4a
toluene
C4a
C4a
C4b
1,4-dioxane
DMSO
PEG+H2Oc
aReaction conditions: mixture of 1.0 equiv. of each of dimedone (1
mmol), isatin (1 mmol), and p-toluidine (1 mmol) with
dimethylacetylenedicarboxylate (1.3 mmol) were heated with stirring in
presence of different catalysts (10 mol% for heterogeneous catalysts and 5
30 mol% of calixarene catalysts) in 2 ml of solvent. Isolated yield. (0.5 ml
PEG-400 + 1.5 ml H2O). NF= not found.
Table 3: Effect of various reaction parametersa
H3C
b
c
O
O
NH2
O
N
Several solvents like DMSO, toluene, 1,4-dioxane, water and
PEG+H2O (0.5 ml PEG-400 + 1.5 ml H2O) were tested as
reaction medium. In case of heterogeneous catalysts, little amount
35 (15-18%) of product was generated due to some acidity in water.
In comparison between organic catalysts in water, C4a showed
comparatively better result. Actually we got the best result in 1:3
conditions
O
MeOOC
COOMe
N
H
O
N
CH3
MeOOC
COOMe
6
5a
7a
8a
9a
25
H
O
CH3
O
SMSNP
Si
S
COOH
O
O
Si
S
COOH
PSNP
O
O
(a) SMSNP-CA
(b) PSNP-CA
O
O
OH
OH
O
O
O
O
HO
OH
HO
OH
OH
OH
( c) Citric acid
(d) Isocitric acid
O
O
O
O
H
O
H3C
H
COOH
HOOC
(f)
COOH
(e) MC4a
Calix 4d
Figure 5: silica nanoparticle supported carboxylic acid (a) SMSNP-CA &
(b) PSNP-CA, tricarboxylic acid (c) citric acid & (d) isocitric acid,
monomer of C4a (e) MC4a and dicarboxylate calixarene (f) C4d12
40

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DOI: 10.1039/C5GC00156K
H3C
H3C
H3C
80
60
40
20
0
O
O
O
N
N
N
Br
Cl
N
N
N
MeOOC
COOMe
MeOOC
COOMe
MeOOC
COOMe
9c (70%)
9a (76%)
9b (72%)
OMe
O
O
N
N
O
H3C
MeOOC
Br
H3C
0
4
8
12
16
20
Br
N
Time (h)
N
N
N
COOMe
9e (71%)
Figure 6: Selective productivity of compound 9a vs. time plot using C4a
MeOOC
COOMe
9d (75%)
MeOOC
COOMe
9f (75%)
as the catalyst
OMe
MeO
80
75
70
65
60
55
50
45
40
O
O
O
N
N
N
Br
N
N
N
MeOOC
COOMe
MeOOC
COOMe
9h (71%)
MeOOC
COOMe
9i (77%)
9g (72%)
MeO
2
4
6
8
10
O
O
O
Amount of catalyst (mol%)
N
N
N
Br
Br
N
N
N
5
Figure 7: yields at different catalyst loading
MeOOC
COOMe
MeOOC
9l (70%)
COOMe
MeOOC
H3C
COOMe
9k (74%)
9j (74%)
H3C
R2
CH3
O
O
O
NH2
O
N
O
O
5 mol% C4a,
R1
N
R1
N
PEG+H2O
O
N
R3OOC
COOR3
N
Br
100 ºC, 12 h
stirring
H
O
N
R2
R1=H, 5a
R1=Br, 5b
R1=Cl, 5c
R3=Me, 8a
R3=Et, 8b
R3OOC
COOR3
N
6
7
N
N
9
R2= electron withdrawing
or donating substituent
EtOOC
COOEt
EtOOC
COOEt
9n (72%)
EtOOC
COOEt
9o (74%)
9m (75%)
OMe
O
O
N
N
O
Br
N
N
N
EtOOC
COOEt
9q (71%)
N
EtOOC
COOEt
EtOOC
H3C
COOEt
9p (73%)
9r (71%)
OMe
OMe
CH3
O
O
O
N
N
N
Cl
Br
N
N
N
EtOOC
COOEt
EtOOC
COOEt
EtOOC
COOEt
9t (67%)
9s (69%)
9u (77%)

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DOI: 10.1039/C5GC00156K
CH3
N
CH3
N
H3C
25 After our successful efforts, we shifted our attention to generalize
this approach with various substituted isatins, amines and
dialkylacetylenedicarboxylates and all were successful towards
the library synthesis of an assembly of compounds and the results
are shown in Scheme 3.
H3C
O
O
O
N
Br
Cl
N
N
N
EtOOC
COOEt
9v (73%)
30 We examined the reactivity of electron deficient 5-chloro or 5-
bromo isatin which resulted in moderate yields (67-72%) of the
product. The behaviour of electronic variation to the amine part
was also observed. So, the starting materials that are selected in
Scheme 3, contained a wide range of functionalities with the
35 purpose to maximize diversity to a reasonable extent. As
expected, using the standard set of the reaction conditions, benzyl
amines also incorporated assortment in acridine derivative (10,
Scheme 4) with a good yield of 72-75% range. Aliphatic
substitutions on pyrrole counterpart were also carefully
40 investigated employing aliphatic amines (Scheme 4).
EtOOC
COOEt
EtOOC
COOEt
9w (70%)
9x (73%)
MeO
MeO
O
O
O
N
N
N
Br
Br
N
N
N
EtOOC
Cl
COOEt
EtOOC
COOEt
9a' (74%)
EtOOC
COOEt
9y (70%)
9z (76%)
Cl
Br
R4
O
O
O
O
N
O
O
R1
R1
N
N
N
O
R4 NH2
R3OOC
COOR3
Br
N
H
O
N
R4 = benzyl or
aliphatic group
R3=Me or Et
R1=H or Br or Cl
R3OOC
N
COOR3
N
N
10
EtOOC
COOEt
9c' (67%)
EtOOC
COOEt
9d' (68%)
EtOOC
COOEt
9b' (68%)
O
O
O
O
N
N
N
N
Br
Br
N
N
N
N
EtOOC
COOEt
9e' (74%)
MeOOC
COOMe
10c (70%)
EtOOC
COOEt
COOEt
EtOOC
10b (70%)
10a (73%)
CH3
CH3
Scheme 3: C4a catalyzed synthesis of some acridine derivatives with
aromatic substitution
O
N
PEG-400 and H2O mixture as the PEG, being a phase-transfer-
catalyst, increases the missibility of the catalyst in water. Where
as in DMSO the four ring containing pyrrolo fused acridine
intermediate (D) was obtained.
O
O
N
N
Br
5
N
EtOOC
COOEt
N
N
10f (74%)
MeOOC
COOMe MeOOC
COOMe
Temperature also played a crucial role to the fruitfulness of five
ring fusion which was reflected from the reaction occurring at
80ºC employing C4a in PEG+H2O producing only the same
10d (75%)
10e (72%)
O
O
10 intermediate (D). 100ºC was the critical temperature for this
reaction. The kinetics of the reaction i.e., the dependence of the
reaction on time was also studied (Figure 6), which revealed the
reaction completion time was just 12 h and further increase in
time up to 18 h did not hamper the amount of the product 9a
15 formation.
N
O
N
N
Br
Br
N
N
N
EtOOC
10i (67%)
COOEt
EtOOC
COOEt
EtOOC
COOEt
10h (68%)
10g (72%)
To determine the appropriate amount of the catalyst, the synthesis
of the product (9a) was carried out in the presence of various
amounts of catalyst in (PEG+H2O) at 100 ºC. Figure 7 shows a
striking increase in productivity consistent with the increase in
20 the quantity of the catalyst up to 5 mol%. No significant increase
in the yield was observed with a further higher amount of
catalyst. With the intention of using the minimum amount of the
catalyst, we have been restricted to 5 mol% for continuation
purpose.
Scheme 4: C4a catalyzed synthesis of some acridine derivatives with
aliphatic substitution
45 The structure of newly generated five ring fused acridine
derivative was confirmed by single crystal X-ray analysis of
compound 9a (crystallized from EtOAc) (Figure 8).
Reprocessing of catalyst recovered from column was investigated
and it had been seen that the catalytic activity did not hamper the

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DOI: 10.1039/C5GC00156K
yield notably up to five cycles that was reflected in Table 3. Thus 25 ring closer of D with acetylenedicarboxylate forms intermediate
the catalyst had the potential of reworking at least five times. The
1H NMR data of the catalyst after each 2 cycles was taken to
prove that it still remains the same and the NMR data is given in
the supplementary section which reveals that after recycling, the
catalysts remains unchanged.
E that undergoes aerial oxidation to produce the desired product.
We also got the same final product starting from the intermediate
D.
5
Table 3: Recyclability of the C4a for the synthesis of 9a
No of cycles a
yield b (%)
1
2
3
4
5
6
76
75
75
74
73
70
a Reaction was carried out with recovered catalyst. b Isolated yield.
H
N
O
O
O
O
H2N
OH
R
COOH
HO
O
NH
R
6
A
COOH
H
N
HOOC
HO
OH
O
COOH
HOOC
O
O
H
HOOC
NH
H
N
30
Figure 8: X-ray single crystal structure of 9a. (CCDC 1014291)
O
O
HOOC
HO
COOH
N
O
H
R
B
COO
OH
4
OH
H
OOC
x
l
i
H
Conclusions
a
N
O
C
R
HOOC
In summary, we have developed the first, efficient and novel one
step strategy of incorporation of carboxylic acid group at the
lower rim of simple p-tert-butylcalix[4]arene with high
O
HOOC
HO
O
R
H2N
O
COO
H
N
HOOC
C
35 throughput yield upon 100% conversion. The most important
application of this newly synthesized calixarene grafted acid was
investigated towards multiring conjunction as recyclable
organocatalyst in organic synthesis. A fruitful result evident from
this investigation is the generation of a new series of five ring
40 fused acridine derivatives. So, in this paper, we report a new and
competent methodology for the synthesis of that core in high
yields in a multicomponent fashion from simple commercially
available reagents. The use of the recyclable catalyst makes this
organic protocol more environmentally benign from the point of
45 catalytic chemistry. This new entry to the calixrene member is
hoped to stride towards sensing and hosting of many inorganic
and organic compounds along with organocatalysis. Also our new
series of diverse acridine derivatives may bright a part of
medicinal chemistry.
a
l
i
x
COOH
4
O
N
OH
N
R
O
H
H
COOH
D
O
C
R
O
R
O
O
R
N
N
N
R1
R1
areal
oxydation
N
N
N
R3OOC
COOR3
H
R3OOC
H
COOR3
E
R'
9 or 10
OOC
HO
R'
O
C
a
O
l
i
x
4
HOOC
10
Scheme 5: Suggested mechanism for the C4a catalyzed synthesis of
acridine derivative [the probable weak interactions of starting materials
and the aromatic groups of the C4a have not been shown in mechanism
due to shake of simplicity and also all amines are represented as R-NH2
50 Experimental section
15 for the same simplicity reason]
Synthesis of p-tert-butylcalix[4]arene:
The mechanism of this multicomponent reaction (Scheme 5)
expectedly passes through a series of condensations followed by
the ring closure cascade reactions. Intermediate B may be formed
via condensation of initially formed enaminoketone A with isatin.
20 Then the catalyst promoted intramolecular ring opening in
concurrence with ring closing involving B to produce C which
upon further condensation produce intermediate D. The structure
of D is confirmed from the NMR spectrum of the major product
(D, see SI), isolated by quenching the reaction after 1 h. The third
p-tert-Butylcalix[4]arene was synthesized from the mixture of p-
tert-butylphenol (2 g, 13.32 mmol), 37% formaldehyde solution
(1.24 mL, 16.6 mmol of HCHO), and NaOH (240 mg, 0.6 mmol)
55 according to our reported procedure.4a
Synthesis of 25-hydroxy-26, 27, 28-tris(1-carboxy-1-
methylmethoxy)-p-tert-butylcalix[4]arene (C4a):

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DOI: 10.1039/C5GC00156K
p-tert-Butylcalix[4]arene (200mg, 0.3 mmol) was mixed with
NaH (120 mg, 5 mmol) in a 25 ml round bottom flask, 10 ml of
dry DMF was added to it. The mixture was allowed to stir for 30
mins at room temperature (25-30 ºC). 2-Bromopropionic acid (3
ml, 3.3 mmol) was diluted with dry DMF (5 ml) up to 37.5%.
Then it was added drop wise (1 drop per 5 sec) maintaining the
temperature at 20-25 ºC. After the complete addition the reaction
mixture was stirred for 4 h. As the reaction progressed, the
suspended particles changed into a form of viscous mass. The
114.7, 76.6, 53.4, 34.0, 33.9, 33.5, 33.0, 32.2, 31.9, 31.5, 31.2,
29.7, 29.2, 22.7, 21.2; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd
for [C49H64O6Na]: 771.4595. Found 771.4495. Anal. calcd. for
C49H64O6; C: 78.57; H: 8.61. Found: C: 78.54; H: 8.63.
5
60 General procedure for the synthesis of five ring fused
acridine derivatives (all entries of Scheme 3 & 4):
First 43 mg (5 mol%) of C4a was dissolved in 2ml of PEG+H2O
(1:3) (v/v) by slight heating and stirring. Then 5,5-dimethyl-1,3-
cyclohexaedione (140 mg, 1 mmol), aromatic or aliphatic amine
10 disappearance of starting p-tert-Butylcalix[4]arene was checked
by TLC. After complete conversion the reaction mixture was
placed in an ice bath and was quenched via acidification using
5% HCl solution. Then 20 ml of chilled water was added to it and
we got the crude product by filtration. 245 mg (92%) pure
15 product, color less solid was gained via column chromatography
at 25% ethyl acetate in petroleum ether as eluent. mp. 298 ºC; IR
(KBr, υ cm-1): 3384, 2962, 2874, 2365, 1686, 1479, 1362, 1194,
1106, 1043. 1H NMR (300 MHz, CDCl3): δ 7.74-7.61 (m, 1H, -
OH), 7.20-7.14 (m, 4H, Ar-H), 7.08-7.00 (m, 4H, Ar-H), 4.80 (br
20 s, 1H, -CH), 4.43-4.39 (m, 4H, -CH2), 4.20-3.95 (m, 2H, -CH),
3.45-3.31 (m, 4H, -CH2),1.66 (br s, 3H, -CH3),1.55 (d, J = 8.4
Hz, 4H, -CH3), 1.66 (br s, 2H, -CH3), 1.27-1.15 (m, 36H, -CH3);
13C NMR (75 MHz, CDCl3): δ 178.0, 177.7, 177.3, 176.9, 148.9,
148.8, 148.3, 147.3, 142.8, 135.2, 134.9, 134.4, 134.1, 132.0,
25 126.9, 126.2, 125.4, 125.2, 125.0, 83.8, 82.7, 82.0, 78.7, 34.1,
34.1, 33.9, 32.3, 32.0, 31.6, 31.4, 31.2, 30.3, 17.9, 17.3, 16.7,
65 (1
mmol),
isatin
(147
mg,
1
mmol)
and
dialkylacetylenedicarboxylate (1.3 mmol) were added to the
solution. This reaction mixture was heated to 100 ºC and stirred
for 12 h at that temperature. The progress of the reaction was
measured by TLC and the time of completion was monitored by
70 disappearance of spot for isatin. After that the reaction mixture
was poured into crushed ice and filtered. The residue was
submitted to column chromatography with using 60-120 mesh
silica gel and petroleum ether-ethyl acetate mixture as eluent. We
got the pure products at 5-6% ethyl acetate at petroleum ether and
75 the pure catalyst at 22% ethyl acetate at petroleum ether.
Spectral and Analytical Data of the products:
Dimethyl-4,4-dimethyl-1-oxo-2-p-tolyl-2,4-dihydro-1H-2,6a-
diazacyclopenta[fg]aceanthrylene-5,6-dicarboxylate
(9a):
16.4; HRMS (ESI-TOF) m/z: [M
+
Na]+ Calcd for
Yellow solid (76%), mp. 216 ºC (EtOAc); IR (KBr, υ cm-1):
[C53H68O10Na]: 887.4705. Found 887. 4702. Anal. calcd. for
C53H68O10; C: 73.58; H: 7.92. Found: C: 73.52; H: 7.95.
1
80 2949, 2342, 1718, 1689, 1448, 1326, 1232, 760 ; H NMR (300
MHz, CDCl3): δ 8.51-8.48 (m, 1H, Ar-H), 8.02-7.99 (m, 1H, Ar-
H), 7.52-7.49 (m, 2H, Ar-H), 7.42 (d, J = 8.4 Hz, 2H, Ar-H), 7.34
(d, J = 8.4 Hz, 2H, Ar-H), 5.78 (s, 1H, vinylic-H), 4.13 (s, 3H, -
OCH3), 3.96 (s, 3H, -OCH3), 2.44 (s, 3H, -CH3), 1.68 (s, 6H, -
85 CH3) ; 13C NMR (75 MHz, CDCl3): δ 167.2, 164.4, 164.3, 136.6,
134.0, 133.1, 131.4, 131.0, 129.9, 127.5, 126.4, 125.6, 125.5,
124.7, 123.3, 122.8, 122.1, 119.6, 117.6, 108.3, 53.3, 52.0, 42.5,
28.1, 21.1 ; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
[C29H24N2O5Na]: 503.1577. Found 503.1554. Anal. calcd. for
90 C29H24N2O5; C: 72.49; H: 5.03; N: 5.83. Found: C: 72.41; H:
5.01; N: 5.80.
30 Synthesis of 25, 26, 27, 28-tetrakis(1-carboxy-1-methoxy)-p-
tert-butylcalix[4]arene (C4b):
C4b was synthesized from p-tert-Butylcalix[4]arene at the same
procedure like C4a. 211 mg (80%) pure product, white solid was
gained via column chromatography at 80% ethyl acetate in
35 petroleum ether as eluent. mp. Above 300 ºC; IR (KBr, υ cm-1):
3392, 2961, 2868, 1603, 1736, 1482, 1393, 1193, 1056. 1H NMR
(300 MHz, CDCl3): δ 7.26-7.23 (m, 3H, Ar-H), 7.18-7.02 (m, 3H,
Ar-H), 6.79-6.74 (m, 2H, Ar-H), 4.81-4.21 (m, 14H, -CH2), 3.32
(bs, 2H, -CH2), 1.25-0.94 (m, 36H, -CH3); HRMS (ESI-TOF)
40 m/z: [M + Na]+ Calcd for [C52H64O12Na]: 903.4290. Found
903.4294. Anal. calcd. for C52H64O12; C: 70.89; H: 7.32. Found:
C: 70.85; H: 7.35.
Dimethyl-9-bromo-4,4-dimethyl-1-oxo-2-p-tolyl-2,4-dihydro-
1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-dicarboxylate
(9b): Reddish yellow solid (72%), mp. 252 ºC (EtOAc) ; IR
95 (KBr, υ cm-1): 2950, 2366, 1715, 1677, 1478, 1345, 1281, 992;
1H NMR (300 MHz, CDCl3): δ 8.49 (s, 1H, Ar-H), 8.12 (s, 1H,
Ar-H), 7.34-7.27 (m, 5H, Ar-H), 5.74 (s, 1H, vinylic-H), 3.92 (s,
3H, -OCH3), 3.87 (s, 3H, -OCH3), 2.38 (s, 3H, -CH3), 1.63 (s, 6H,
-CH3) ; 13C NMR (75 MHz, CDCl3): δ 168.4, 162.5, 162.4, 135.5,
100 135.0, 133.1, 132.3, 130.1, 129.9, 128.6, 126.2, 125.3, 125.2,
121.2, 119.1, 117.1, 55.6, 53.3, 52.1, 42.6, 27.8, 21.2; HRMS
(ESI-TOF) m/z: [M + Na]+ Calcd for [C29H23BrN2O5Na]:
581.0683. Found 581.0674. Anal. calcd. for C29H23BrN2O5; C:
62.26; H: 4.14; N: 5.01. Found: C: 62.20; H: 4.11; N: 5.04.
Synthesis of 25, 26, 27-trihydroxy-28-(4-carboxy-1-butoxy)-p-
tert-butylcalix[4]arene (C4c):
45 C4c was synthesized from p-tert-Butylcalix[4]arene at the same
procedure like C4a. 197 mg (85%) pure product, color less
gummy solid was gained via column chromatography at 15%
ethyl acetate in petroleum ether as eluent. IR (KBr, υ cm-1): 3350,
2960, 2870, 1710, 1485, 1362, 1202, 1123.. 1H NMR (300 MHz,
50 CDCl3): δ 10.09 (bs, 1H, -OH), 9.49 (bs, 2H, -OH), 7.01-6.91 (m,
8H, Ar-H), 4.27-4.18 (m, 4H, -CH2), 4.08-4.06 (m, 2H, -CH2),
3.38-3.34 (m, 4H, -CH2), 2.53(t, J = 6.75 Hz, 2H, -CH2), 2.14-
1.99 (m, 4H, -CH2), 1.14-1.12 (m, 36H, -CH3); 13C NMR (75
MHz, CDCl3): δ 177.84, 149.2, 148.4, 148.2, 147.7, 143.6, 143.2,
55 133.4, 128.3, 128.0, 127.6, 126.5, 125.9, 125.8, 125.7, 125.6,
105 Dimethyl-9-chloro-4,4-dimethyl-1-oxo-2-p-tolyl-2,4-dihydro-
1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-dicarboxylate
(9c): Yellow solid (70%), mp. 244 ºC (EtOAc); IR (KBr, υ cm-1):
1
2945, 2401, 1721, 1447, 1326, 1294, 1056; H NMR (300 MHz,

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DOI: 10.1039/C5GC00156K
CDCl3): δ 8.42 (d, J = 4.2 Hz, 1H, Ar-H), 7.79 (d, J = 9.3 Hz, 1H,
Ar-H), 7.50 (dd, J = 8.4 Hz, J = 2.4 Hz, 1H, Ar-H), 7.34-7.24 (m,
4H, Ar-H), 5.72 (s, 1H, vinylic-H), 4.52 (s, 3H, -OCH3), 4.37 (s,
3H, -OCH3), 2.36 (s, 3H, -CH3), 1.59 (s, 6H, -CH3); 13C NMR
dicarboxylate (9g): Yellow solid (72%), mp. 266 ºC (EtOAc); IR
(KBr, υ cm-1): 2927, 2342, 1708, 1621, 1319, 1209, 851; 1H
NMR (300 MHz, CDCl3): δ 8.43 (s, 1H, Ar-H), 7.88 (d, J = 9.3
Hz, 1H, Ar-H), 7.41-7.33 (m, 4H, Ar-H), 7.12-7.05 (m, 1H, Ar-
5
(75 MHz, CDCl3): δ 169.0, 164.5, 164.2, 136.4, 135.2, 134.6, 60 H), 5.41 (s, 1H, vinylic-H), 3.92 (s, 3H, -OCH3), 3.88 (s, 3H, -
134.2, 134.0, 133.6, 131.2, 130.7, 129.4, 127.9, 127.8, 125.3,
122.8, 121.6, 115.2, 113.2, 112.6, 53.4, 52.6, 43.3, 29.3, 21.0;
Anal. calcd. for C29H23ClN2O5; C: 67. 64; H: 4.50; N: 5.44.
Found: C: 67.59; H: 4.51; N: 5.42.
OCH3), 3.80 (s, 3H, -OCH3), 1.60 (s, 6H, -CH3); 13C NMR (75
MHz, CDCl3): δ 167.0, 164.0, 163.8, 160.7, 137.0, 134.2, 131.5,
130.9, 129.8, 127.5, 126.4, 126.1, 124.5, 123.3, 122.9, 122.7,
119.7, 117.7, 112.4, 111.4, 107.4, 55.5, 54.4, 53.7, 42.6, 28.1;
65 Anal. calcd. for C29H23BrN2O6; C: 60.53; H: 4.03; N: 4.87.
Found: C: 60.50; H: 4.05; N: 4.89.
10 Dimethyl-4,4-dimethyl-1-oxo-2-o-tolyl-2,4-dihydro-1H-2,6a-
diazacyclopenta[fg]aceanthrylene-5,6-dicarboxylate
(9d):
Yellow solid (75%), mp. 228 ºC (EtOAc); IR (KBr, υ cm-1):
Dimethyl-2-(4-bromophenyl)-4,4-dimethyl-1-oxo-2,4-dihydro-
1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-dicarboxylate
1
2951, 2355, 1705, 1621, 1436, 1293, 1151, 762; H NMR (300
MHz, CDCl3): δ 8.43-8.40 (m, 1H, Ar-H), 7.95-7.92 (m, 1H, Ar-
(9h): Reddish yellow solid (71%), mp. 258 ºC (EtOAc): IR (KBr,
1
15 H), 7.47-7.42 (m, 2H, Ar-H), 7.31-7.26 (m, 4H, Ar-H), 5.35 (s, 70 υ cm-1): 2969, 2352, 1711, 1591, 1425, 1149, 887; H NMR (300
1H, vinylic-H), 4.04 (s, 3H, -OCH3), 3.87 (s, 3H, -OCH3), 2.18
(s, 3H, -CH3), 1.57(s, 3H, -CH3), 1.56 (s, 3H, -CH3); 13C NMR
(75 MHz, CDCl3): δ 167.4, 164.5, 164.3, 136.9, 134.1, 131.8,
131.4, 128.8, 128.6, 127.6, 126.9, 126.6, 126.4, 125.6, 124.8,
MHz, CDCl3): δ 8.47-8.44 (m, 1H, Ar-H), 7.98-7.95 (m, 1H, Ar-
H), 7.69-7.61 (m, 2H, Ar-H), 7.52-7.38 (m, 4H, Ar-H), 5.79 (s,
1H, vinylic-H), 4.12 (s, 3H, -OCH3), 3.95 (s, 3H, -OCH3), 1.68
(s, 6H, -CH3); Anal. calcd. for C28H21BrN2O5; C: 61.66; H: 3.88;
20 123.3, 123.0, 121.8, 119.7, 117.6, 108.5, 53.4, 52.0, 42.5, 28.1, 75 N: 5.14. Found: C: 61.63; H: 3.87; N: 5.11.
28.0, 18.1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
Dimethyl-2-(4-methoxyphenyl)-4,4-dimethyl-1-oxo-2,4-
[C29H24N2O5Na]: 503.1577. Found 503.1561. Anal. calcd. for
C29H24N2O5; C: 72.49; H: 5.03; N: 5.83. Found: C: 72.43; H:
5.07; N: 5.86.
dihydro-1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-
dicarboxylate (9i): Reddish yellow solid (77%), mp. 236 ºC
(EtOAc); IR (KBr, υ cm-1): 2960, 2297, 1715, 1604, 1502, 1166,
1
25 Dimethyl-9-bromo-4,4-dimethyl-1-oxo-2-o-tolyl-2,4-dihydro-
1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-dicarboxylate
(9e): Yellow solid (71%), mp. 260-262 ºC (EtOAc); IR (KBr, υ
80 955; H NMR (300 MHz, CDCl3): δ 8.59-8.58 (m, 1H, Ar-H),
8.09-8.06 (m, 1H, Ar-H), 7.97-7.94 (m, 2H, Ar-H), 7.44-7.41 (m,
2H, Ar-H),6.98 (d, J = 9 Hz, 1H, Ar-H), 5.71 (s, 1H, vinylic-H),
3.97 (s, 3H, -OCH3), 3.87 (s, 3H, -OCH3), 3.85 (s, 3H, -OCH3),
1.67 (s, 6H, -CH3); 13C NMR (75 MHz, CDCl3): δ 169.6, 169.0,
1
cm-1): 3011, 2301, 1719, 1655, 1391, 1293, 1175, 769; H NMR
(300 MHz, CDCl3): δ 8.58 (s, 1H, Ar-H), 8.08-8.07 (m, 1H, Ar-
30 H), 7.79-7.78 (m, 2H, Ar-H), 7.66-7.65 (m, 2H, Ar-H), 7.50-7.49 85 167.9, 167.2, 138.6, 137.2, 133.8, 133.5, 131.2, 130.7, 129.3,
(m, 1H, Ar-H), 5.68 (s, 1H, vinylic-H), 3.92 (s, 3H, -OCH3), 3.86
(s, 3H, -OCH3), 2.11 (s, 3H, -CH3), 1.56 (s, 6H, -CH3); 13C NMR
(75 MHz, CDCl3): δ 166.7, 165.0, 164.8, 138.1, 136.6, 134.4,
133.3, 132.0, 131.9, 130.6, 129.9, 127.0, 126.8, 126.3, 124.3,
35 123.4, 123.2, 122.3, 119.9, 115.2, 108.6, 53.9, 52.9, 43.7, 27.9,
127.9, 127.8, 127.5, 122.8, 121.6, 115.2, 113.1, 110.8, 53.4, 52.7,
52.4, 43.1, 28.5; Anal. calcd. for C29H24N2O6; C: 70.15; H: 4.87;
N: 5.64. Found: C: 70.12; H: 4.85; N: 5.66.
Dimethyl-9-bromo-2-(4-methoxyphenyl)-4,4-dimethyl-1-oxo-
90 2,4-dihydro-1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-
dicarboxylate (9j): Yellow solid (74%), mp. 266 ºC (EtOAc); IR
(KBr, υ cm-1): 2939, 2331, 1712, 1598, 1365, 1203, 1012; 1H
NMR (300 MHz, CDCl3): δ 8.52 (d, J = 2.1 Hz, 1H, Ar-H), 7.86
(d, J = 9.3 Hz, 1H, Ar-H), 7.52-7.48 (m, 1H, Ar-H), 7.33 (d, J = 9
95 Hz, 2H, Ar-H), 6.97 (d, J = 9 Hz, 2H, Ar-H), 5.67 (s, 1H, vinylic-
H), 4.02 (s, 3H, -OCH3), 3.87 (s, 3H, -OCH3), 3.80 (s, 3H, -
OCH3), 1.58 (s, 6H, -CH3); 13C NMR (75 MHz, CDCl3): δ 166.9,
164.4, 163.9, 158.4, 132.9, 132.0, 131.1, 130.3, 128.7, 128.2,
127.7, 127.0, 126.9, 125.5, 124.7, 124.4, 123.7, 122.6, 121.7,
21.1; HRMS (ESI-TOF) m/z: [M
+
Na]+ Calcd for
[C29H23BrN2O5Na]: 581.0683. Found 581.0704. Anal. calcd. for
C29H23BrN2O5; C: 62.26; H: 4.14; N: 5.01. Found: C: 62.28; H:
4.15; N: 4.99.
40 Dimethyl-2-(3-methoxyphenyl)-4,4-dimethyl-1-oxo-2,4-
dihydro-1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-
dicarboxylate (9f): Yellow solid (75%), mp. 232 ºC (EtOAc); IR
(KBr, υ cm-1): 2973, 2347, 1702, 1500, 1425, 1228, 731; 1H
NMR (300 MHz, CDCl3): δ 8.52-8.48 (m, 1H, Ar-H), 8.00-7.96
45 (m, 1H, Ar-H), 7.52-7.49 (m, 2H, Ar-H), 7.43 (t, J = 8.4 Hz, 1H, 100 120.5, 120.1, 119.2, 114.6, 114.1, 107.4, 55.5, 53.4, 52.1, 42.6,
Ar-H), 7.12-7.10 (m, 2H, Ar-H), 6.93-6.89 (m, 1H, Ar-H), 5.84
(s, 1H, vinylic-H), 4.12 (s, 3H, -OCH3), 3.95 (s, 3H, -OCH3),
3.88 (s, 3H, -OCH3), 1.67 (s, 6H, -CH3); 13C NMR (75 MHz,
CDCl3): δ 167.1, 164.4, 164.4, 160.3, 136.9, 134.0, 131.6, 130.8,
50 129.9, 129.6, 127.6, 126.5, 125.7, 124.6, 123.4, 122.8, 122.7,
119.6, 117.7, 117.6, 112.5, 111.4, 108.2, 55.5, 53.4, 52.1, 42.6,
28.1; Anal. calcd. for C29H24N2O6; C: 70.15; H: 4.87; N: 5.64.
Found: C: 70.18; H: 4.85; N: 5.69.
28.1; Anal. calcd. for C29H23BrN2O6; C: 60.53; H: 4.03; N: 4.87.
Found: C: 60.57; H: 4.01; N: 4.90.
Dimethyl-2-(2-isopropylphenyl)-4,4-dimethyl-1-oxo-2,4-
dihydro-1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-
105 dicarboxylate (9k): Yellow solid (74%), mp. 240 ºC (EtOAc);
1
IR (KBr, υ cm-1): 2921, 2402, 1699, 1614, 1298, 1087, 934; H
NMR (300 MHz, CDCl3): δ 8.39 (dd, J = 6.2 Hz, J = 3.3 Hz, 1H,
Ar-H), 7.92 (dd, J = 6.3 Hz, J = 3.3 Hz, 1H, Ar-H), 7.43-7.34 (m,
3H, Ar-H), 7.27-7.17 (m, 3H, Ar-H), 5.29 (s, 1H, vinylic-H),
110 4.02 (s, 3H, -OCH3), 3.85 (s, 3H, -OCH3), 2.88-2.83 (m, 1H, -
Dimethyl-9-bromo-2-(3-methoxyphenyl)-4,4-dimethyl-1-oxo-
55 2,4-dihydro-1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-

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DOI: 10.1039/C5GC00156K
CH), 1.55 (s, 3H, -CH3), 1.52 (s, 3H, -CH3), 1.14 (d, J = 6.9 Hz,
3H, -CH3), 1.06 (d, J = 6.6 Hz, 3H, -CH3);13C NMR (75 MHz,
CDCl3): δ 167.9, 164.4, 164.2, 147.8, 134.8, 134.0, 132.5, 131.6,
129.5, 129.4, 129.3, 129.2, 127.6, 127.5, 126.7, 126.5, 126.3,
vinylic-H), 4.52 (q, J = 7.2 Hz, 2H, -OCH2), 4.34 (q, J = 7.2 Hz,
2H, -OCH2), 2.18 (s, 3H, -CH3), 1.58 (s, 6H, -CH3), 1.42 (t, J =
7.2 Hz, 3H, -CH3), 1.36 (t, J = 7.2 Hz, 3H, -CH3); 13C NMR (75
MHz, CDCl3): δ 167.5, 164.1, 163.9, 136.9, 134.2, 131.4, 131.3,
5
125.5, 125.1, 124.7, 124.3, 123.2, 123.0, 122.7, 121.5, 119.6, 60 128.8, 128.6, 127.4, 126.9, 126.5, 126.3, 126.0, 124.6, 123.2,
117.6, 108.3, 53.3, 52.0, 42.4, 28.0, 27.9, 23.9, 23.6; Anal. calcd.
for C31H28N2O5; C: 73.21; H: 5.55; N: 5.51. Found: C: 73.15; H:
5.51; N: 5.56.
123.0, 121.9, 119.8, 117.7, 108.3, 62.7, 61.1, 42.5, 28.0, 18.1,
14.2, 14.0; Anal. calcd. for C31H28N2O5; C: 73.21; H: 5.55; N:
5.51. Found: C: 73.26; H: 5.53; N: 5.48.
Dimethyl-9-bromo-2-(2-isopropylphenyl)-4,4-dimethyl-1-oxo-
Diethyl-4,4-dimethyl-1-oxo-2-phenyl-2,4-dihydro-1H-2,6a-
10 2,4-dihydro-1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-
dicarboxylate (9l): Yellow solid (70%), mp. 280 ºC (EtOAc); IR
(KBr, υ cm-1): 2960, 1697, 1627, 1428, 1225, 1036, 725; 1H
NMR (300 MHz, CDCl3): δ 8.42 (d, J = 2.4 Hz, 1H, Ar-H), 7.86
(d, J = 10.2 Hz, 1H, Ar-H), 7.52 (d, J = 4.5 Hz, 1H, Ar-H), 7.41-
65 diazacyclopenta[fg]aceanthrylene-5,6-dicarboxylate
(9p):
Yellow solid (73%), mp. 234 ºC (EtOAc); IR (KBr, υ cm-1):
1
2965, 1708, 1642, 1464, 1192, 1015, 991; H NMR (300 MHz,
CDCl3): δ 8.50-8.46 (m, 1H, Ar-H), 8.09-8.06 (m, 1H, Ar-H),
7.51-7.46 (m, 2H, Ar-H), 7.36-7.32 (m, 5H, Ar-H), 5.71 (s, 1H,
15 7.38 (m, 2H, Ar-H), 7.28-7.20 (m, 2H, Ar-H), 5.32 (s, 1H, 70 vinylic-H), 4.59 (q, J = 7.2 Hz, 2H, -OCH2), 4.44 (q, J = 7.2 Hz,
vinylic-H), 4.04 (s, 3H, -OCH3), 3.89 (s, 3H, -OCH3), 2.85-2.81
(m, 1H, -CH), 1.56 (s, 6H, -CH3), 1.17 (d, J = 8.4 Hz, 3H, -CH3),
1.07 (d, J = 5.7 Hz, 3H, -CH3); HRMS (ESI-TOF) m/z: [M +
Na]+ Calcd for [C31H27BrN2O5Na]: 531.1890. Found 531.1856.
2H, -OCH2), 1.67 (s, 6H, -CH3), 1.49 (t, J = 7.2 Hz, 3H, -CH3),
1.43 (t, J = 7.2 Hz, 3H, -CH3); 13C NMR (75 MHz, CDCl3): δ
166.6, 163.1, 162.0, 136.7, 135.8, 133.2, 132.6, 132.3, 130.9,
129.8, 126.8, 126.6, 124.4, 122.6, 120.4, 119.2, 118.2, 117.5,
20 Anal. calcd. for C31H27BrN2O5; C: 63.38; H: 4.63; N: 4.77. 75 113.9, 112.6, 112.0, 62.6, 61.3, 41.2, 29.7, 14.2, 14.0; Anal.
Found: C: 63.35; H: 4.67; N: 4.72.
calcd. for C30H26N2O5; C: 72.86; H: 5.30; N: 5.66. Found: C:
72.80; H: 5.31; N: 5.68.
Diethyl-4,4-dimethyl-1-oxo-2-p-tolyl-2,4-dihydro-1H-2,6a-
diazacyclopenta[fg]aceanthrylene-5,6-dicarboxylate
(9m):
Diethyl-9-bromo-4,4-dimethyl-1-oxo-2-phenyl-2,4-dihydro-
1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-dicarboxylate
Yellow solid (75%), mp. 188 ºC (EtOAc); IR (KBr, υ cm-1):
25 2932, 1700, 1514, 1249, 1096, 791; 1H NMR (300 MHz, CDCl3): 80 (9q): Yellow solid (71%), mp. 254 ºC (EtOAc); IR (KBr, υ cm-1):
δ 8.53-8.51 (m, 1H, Ar-H), 8.04-8.02 (m, 1H, Ar-H), 7.52-7.50
(m, 2H, Ar-H), 7.42 (d, J = 8.4 Hz, 2H, Ar-H), 7.34 (d, J = 8.1
Hz, 2H, Ar-H), 5.77 (s, 1H, vinylic-H), 4.60 (q, J = 7 Hz, 2H, -
OCH2), 4.43 (q, J = 7 Hz, 2H, -OCH2), 2.44 (s, 3H, -CH3), 1.69
2956, 1702, 1631, 1501, 1203, 864; 1H NMR (300 MHz, CDCl3):
δ 8.61 (d, J = 2.1 Hz, 1H, Ar-H), 8.00 (d, J = 9.3 Hz, 1H, Ar-H),
7.48 (d, J = 8.7 Hz, 1H, Ar-H), 7.32-7.22 (m, 5H, Ar-H), 5.66 (s,
1H, vinylic-H), 4.54 (q, J = 7.2 Hz, 2H, -OCH2), 4.39 (q, J = 7.2
30 (s, 6H, -CH3), 1.50 (t, J = 7.2 Hz, 3H, -CH3), 1.44 (t, J = 7.2 Hz, 85 Hz, 2H, -OCH2), 1.62 (s, 6H, -CH3), 1.44 (t, J = 7.2 Hz, 3H, -
3H, -CH3); 13C NMR (75 MHz, CDCl3): δ 167.4, 164.0, 163.9,
148.6, 136.6, 134.1, 131.6, 129.9, 127.4, 126.5, 126.4, 125.5,
123.2, 122.9, 122.2, 117.6, 117.1, 62.7, 61.2, 42.6, 22.6, 14.2,
14.1; Anal. calcd. for C31H28N2O5; C: 73.21; H: 5.55; N: 5.51.
35 Found: C: 73.25; H: 5.58; N: 5.49.
CH3), 1.38 (t, J = 7.2 Hz, 3H, -CH3); 13C NMR (75 MHz,
CDCl3): δ 168.4, 164.2, 164.1, 141.2, 133.9, 131.2, 127.2, 126.4,
126.3, 124.7, 123.1, 122.6, 120.7, 117.7, 108.8, 62.7, 61.2, 42.3,
28.1, 20.2, 14.2, 14.0; Anal. calcd. for C30H25BrN2O5; C: 62.84;
90 H: 4.39; N: 4.89. Found: C: 62.80; H: 4.35; N: 4.93.
Diethyl-9-bromo-4,4-dimethyl-1-oxo-2-p-tolyl-2,4-dihydro-
1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-dicarboxylate
(9n): Reddish yellow solid (72%), mp. 225 ºC (EtOAc); IR (KBr,
Diethyl-2-(3-methoxyphenyl)-4,4-dimethyl-1-oxo-2,4-dihydro-
1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-dicarboxylate
(9r): Yellow solid (71%), mp. 236 ºC (EtOAc); IR (KBr, υ cm-1):
1
1
υ cm-1): 3001, 1708, 1540, 1122, 1096, 791; H NMR (300 MHz,
3001, 1711, 1589, 1364, 1115, 992, 735; H NMR (300 MHz,
40 CDCl3): δ 8.54 (d, J = 2.1 Hz, 1H, Ar-H), 7.88 (d, J = 9 Hz, 1H, 95 CDCl3): δ 8.43-8.41 (m, 1H, Ar-H), 7.96-7.92 (m, 1H, Ar-H),
Ar-H), 7.50 (dd, J = 9.2 Hz, J = 2.6 Hz, 1H, Ar-H), 7.33-7.24 (m,
4H, Ar-H), 5.72 (s, 1H, vinylic-H), 4.49 (q, J = 7.2 Hz, 2H, -
OCH2), 4.34 (q, J = 7.2 Hz, 2H, -OCH2), 2.36 (s, 3H, -CH3), 1.59
(s, 6H, -CH3), 1.43-1.33 (m, 6H, -CH3); 13C NMR (75 MHz,
7.44-7.41 (m, 2H, Ar-H), 7.39-7.33 (m, 1H, Ar-H), 7.05-7.03 (m,
2H, Ar-H), 6.85-6.82 (m, 1H, Ar-H), 5.76 (s, 1H, vinylic-H), 4.52
(q, J = 7.2 Hz, 2H, -OCH2), 4.34 (q, J = 7.2 Hz, 2H, -OCH2), 3.81
(s, 3H, -OCH3), 1.61 (s, 6H, -CH3), 1.44-1.34 (m, 6H, -CH3); 13
C
45 CDCl3): δ 166.8, 164.0, 163.5, 136.7, 133.0, 132.2, 130.9, 130.2, 100 NMR (75 MHz, CDCl3): δ 167.0, 164.0, 163.9, 160.3, 137.0,
129.9, 128.8, 125.4, 124.5, 123.6, 122.8, 120.6, 120.1, 119.2,
107.3, 62.8, 61.3, 42.6, 28.1, 21.1, 14.2, 14.0; Anal. calcd. for
C31H27BrN2O5; C: 63.38; H: 4.63; N: 4.77. Found: C: 63.35; H:
4.60; N: 4.79.
134.1, 131.7, 130.8, 129.9, 127.5, 126.4, 126.2, 124.4, 123.3,
122.8, 122.7, 119.7, 117.7, 112.5, 111.4, 62.7, 61.2, 55.5, 42.6,
28.1, 14.2, 14.0; Anal. calcd. for C31H28N2O6; C: 70.98; H: 5.38;
N: 5.34. Found: C: 71.01; H: 5.33; N: 5.38.
50 Diethyl-4,4-dimethyl-1-oxo-2-o-tolyl-2,4-dihydro-1H-2,6a-
105 Diethyl-9-bromo-2-(3-methoxyphenyl)-4,4-dimethyl-1-oxo-
2,4-dihydro-1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-
dicarboxylate (9s): Yellow solid (69%), mp. 248 ºC (EtOAc); IR
diazacyclopenta[fg]aceanthrylene-5,6-dicarboxylate
(9o):
Reddish yellow solid (74%), mp. 185 ºC (EtOAc); IR (KBr, υ cm-
1): 2940, 1710, 1634, 1321, 1156, 1032, 828; 1H NMR (300 MHz,
CDCl3): δ 8.43-8.40 (m, 1H, Ar-H), 7.97-7.94 (m, 1H, Ar-H),
1
(KBr, υ cm-1): 2977, 1703, 1605, 1399, 1011, 903, 814; H NMR
(300 MHz, CDCl3): δ 8.52 (s, 1H, Ar-H), 7.94-7.85 (m, 1H, Ar-
55 7.46-7.41 (m, 2H, Ar-H), 7.31-7.26 (m, 4H, Ar-H), 5.34 (s, 1H, 110 H), 7.52-7.49 (m, 1H, Ar-H), 7.37-7.31 (m, 1H, Ar-H), 7.09-7.00

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DOI: 10.1039/C5GC00156K
(m, 2H, Ar-H), 6.90-6.82 (m, 1H, Ar-H), 5.79 (s, 1H, vinylic-H),
4.49 (q, J = 7.2 Hz, 2H, -OCH2), 4.34 (q, J = 7.2 Hz, 2H, -OCH2),
3.79 (s, 3H, -OCH3), 1.60 (s, 6H, -CH3), 1.43-1.33 (m, 6H, -
CH3); 13C NMR (75 MHz, CDCl3): δ 166.6, 163.9, 163.5, 160.3,
(300 MHz, CDCl3): δ 8.43 (d, J = 2.7 Hz, 1H, Ar-H), 8.01 (d, J =
9.3 Hz, 1H, Ar-H), 7.42 (dd, J = 9.2 Hz, J = 2.6 Hz, 1H, Ar-H),
7.29-7.25 (m, 2H, Ar-H), 7.21-7.18 (m, 1H, Ar-H), 5.78 (s, 1H,
vinylic-H), 4.57 (q, J = 7.2 Hz, 2H, -OCH2), 4.42 (q, J = 7.2 Hz,
5
136.7, 133.0, 132.2, 130.3, 130.1, 129.9, 128.7, 126.5, 126.1, 60 2H, -OCH2), 2.33 (s, 3H, -CH3), 2.32 (s, 3H, -CH3),1.67 (s, 6H, -
124.4, 123.7, 123.4, 120.6, 120.1, 119.2, 117.6, 112.6, 111.3,
107.1, 62.8, 61.3, 55.5, 42.7, 28.0, 14.1, 14.0; Anal. calcd. for
C31H27BrN2O6; C: 61.70; H: 4.51; N: 4.64. Found: C: 61.76; H:
4.47; N: 4.60.
CH3), 1.48 (t, J = 7.2 Hz, 3H, -CH3), 1.43 (t, J = 7.2 Hz, 3H, -
CH3); 13C NMR (75 MHz, CDCl3): δ 166.9, 164.0, 163.5, 137.8,
135.5, 133.1, 132.5, 132.2, 131.0, 130.3, 127.3, 126.8, 125.9,
125.7, 124.6, 124.2, 123.6, 122.9, 122.9, 120.6, 119.0, 107.4,
65 62.7, 61.3, 42.6, 28.1, 19.9, 19.4, 14.2, 14.0; Anal. calcd. for
C32H29ClN2O5; C: 69.00; H: 5.25; N: 5.03. Found: C: 69.07; H:
5.22; N: 4.99.
10 Diethyl-9-chloro-2-(3-methoxyphenyl)-4,4-dimethyl-1-oxo-
2,4-dihydro-1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-
dicarboxylate (9t): Yellow solid (67%), mp. 242 ºC (EtOAc); IR
(KBr, υ cm-1): 2966, 1706, 1595, 1245, 1156, 863; 1H NMR (300
MHz, CDCl3): δ 8.38 (d, J = 2.4 Hz, 1H, Ar-H), 7.94 (d, J = 9.3
Diethyl-2-(2-isopropylphenyl)-4,4-dimethyl-1-oxo-2,4-
dihydro-1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-
15 Hz, 1H, Ar-H), 7.38-7.32 (m, 2H, Ar-H), 7.03-7.01 (m, 2H, Ar- 70 dicarboxylate (9x): Greenish yellow solid (73%), mp. 224 ºC
H), 6.86-6.82 (m, 1H, Ar-H), 5.80 (s, 1H, vinylic-H), 4.50 (q, J =
7.2 Hz, 2H, -OCH2), 4.34 (q, J = 7.2 Hz, 2H, -OCH2), 3.80 (s,
3H, -OCH3), 1.60 (s, 6H, -CH3), 1.47-1.33 (m, 6H, -CH3); 13C
NMR (75 MHz, CDCl3): δ 166.7, 164.0, 163.5, 160.4, 136.7,
(EtOAc); IR (KBr, υ cm-1): 3004, 1710, 1538, 1206, 998, 811; 1H
NMR (300 MHz, CDCl3): δ 8.50-8.47 (m, 1H, Ar-H), 8.06-8.02
(m, 1H, Ar-H), 7.51-7.45 (m, 4H, Ar-H), 7.36-7.26 (m, 2H, Ar-
H), 5.38(s, 1H, vinylic-H), 4.59 (q, J = 7.2 Hz, 2H, -OCH2), 4.41
20 132.6, 132.3, 130.6, 130.0, 127.4, 125.8, 124.5, 124.2, 123.7, 75 (q, J = 7.2 Hz, 2H, -OCH2), 2.97-2.92 (m, 1H, -CH), 1.65 (s, 3H,
123.3, 119.0, 117.6, 112.6, 111.4, 62.8, 61.3, 55.5, 42.7, 28.1,
14.2, 14.0; Anal. calcd. for C31H27ClN2O6; C: 66.61; H: 4.87; N:
5.01. Found: C: 66.67; H: 4.85; N: 5.04.
-CH3), 1.62 (s, 3H, -CH3), 1.49 (t, J = 7.2 Hz, 3H, -CH3), 1.42 (t,
J = 7.2 Hz, 3H, -CH3), 1.23 (d, J = 6.9 Hz, 3H, -CH3), 1.15 (d, J
= 6.9 Hz, 3H, -CH3); 13C NMR (75 MHz, CDCl3): δ 167.9, 164.0,
163.8, 147.8, 134.1, 132.6, 132.5, 131.7, 129.4, 129.3, 129.2,
80 127.3, 126.7, 126.6, 126.6, 126.5, 126.2, 126.0, 124.5, 123.1,
123.0, 121.6, 119.8, 117.6, 108.1, 62.6, 61.0, 42.4, 28.2, 28.0,
27.9, 23.8, 23.6, 14.1, 14.0; Anal. calcd. for C33H32N2O5; C:
73.86; H: 6.01; N: 5.22. Found: C: 73.90; H: 5.98; N: 5.18.
Diethyl-2-(3,4-dimethylphenyl)-4,4-dimethyl-1-oxo-2,4-
25 dihydro-1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-
dicarboxylate (9u): Reddish yellow solid (77%), mp. 228 ºC
(EtOAc); IR (KBr, υ cm-1): 2973, 1713, 1605, 1273, 1159, 747;
1H NMR (300 MHz, CDCl3): δ 8.43-8.40 (m, 1H, Ar-H), 7.95-
7.92 (m, 1H, Ar-H), 7.42-7.40 (m, 2H, Ar-H), 7.24-7.15 (m, 3H,
Diethyl-9-bromo-2-(2-isopropylphenyl)-4,4-dimethyl-1-oxo-
30 Ar-H), 5.67 (s, 1H, vinylic-H), 4.51 (q, J = 7.2 Hz, 2H, -OCH2), 85 2,4-dihydro-1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-
4.34 (q, J = 7.2 Hz, 2H, -OCH2), 2.27 (s, 3H, -CH3), 2.25 (s, 3H, -
CH3), 1.59 (s, 6H, -CH3), 1.44-1.33 (m, 6H, -CH3); 13C NMR (75
MHz, CDCl3): δ 167.4, 164.0, 163.9, 137.7, 135.4, 134.1, 133.3,
131.5, 131.1, 130.3, 127.4, 126.9, 126.4, 126.3, 126.0, 124.6,
dicarboxylate (9y): Greenish yellow solid (70%), mp. 252 ºC
(EtOAc); IR (KBr, υ cm-1): 3005, 1709, 1622, 1315, 1032, 943;
1H NMR (300 MHz, CDCl3): δ 8.53 (s, 1H, Ar-H), 7.90 (d, J = 9
Hz, 1H, Ar-H), 7.50 (dd, J = 9.2 Hz, J = 2 Hz, 1H, Ar-H), 7.41-
35 123.2, 123.0, 122.9, 122.2, 119.8, 117.6, 108.1, 62.6, 61.1, 42.5, 90 7.38 (m, 2H, Ar-H), 7.28-7.18 (m, 2H, Ar-H), 5.33 (s, 1H,
28.1, 19.9, 19.4, 14.2, 14.0; Anal. calcd. for C32H30N2O5; C:
73.55; H: 5.79; N: 5.36. Found: C: 73.50; H: 5.84; N: 5.34.
vinylic-H), 4.48 (q, J = 6.9 Hz, 2H, -OCH2), 4.33 (q, J = 6.9 Hz,
2H, -OCH2), 2.85-2.82 (m, 1H, -CH), 1.56 (s, 3H, -CH3), 1.53 (s,
3H, -CH3), 1.42-1.32 (m, 6H, -CH3), 1.23-1.14 (m, 6H, -CH3);
13C NMR (75 MHz, CDCl3): δ 167.4, 164.0, 163.4, 147.8, 133.0,
95 132.4, 130.1, 129.4, 129.3, 128.8, 127.0, 126.8, 126.6, 125.9,
124.6, 124.6, 123.6, 122.2, 120.7, 120.0, 119.2, 107.3, 62.7, 61.2,
42.5, 28.0, 27.9, 23.9, 23.6, 14.2, 13.9; Anal. calcd. for
C33H31BrN2O5; C: 64.39; H: 5.08; N: 4.55. Found: C: 64.31; H:
5.04; N: 4.61.
Diethyl-9-bromo-2-(3,4-dimethylphenyl)-4,4-dimethyl-1-oxo-
2,4-dihydro-1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-
40 dicarboxylate (9v): Orange solid (73%), mp. 250 ºC (EtOAc); IR
1
(KBr, υ cm-1): 2961, 1702, 1610, 1277, 1049, 962, 754; H NMR
(300 MHz, CDCl3): δ 8.56-8.54 (m, 1H, Ar-H), 7.90-7.87 (m, 1H,
Ar-H), 7.52-7.48 (m, 1H, Ar-H), 7.22-7.12 (m, 3H, Ar-H), 5.72
(s, 1H, vinylic-H), 4.49 (q, J = 7.2 Hz, 2H, -OCH2), 4.34 (q, J =
45 7.2 Hz, 2H, -OCH2), 2.27 (s, 3H, -CH3), 2.26 (s, 3H, -CH3), 1.59 100 Diethyl-2-(4-methoxyphenyl)-4,4-dimethyl-1-oxo-2,4-dihydro-
(s, 6H, -CH3), 1.43-1.33 (m, 6H, -CH3); 13C NMR (75 MHz,
CDCl3): δ 168.4, 162.9, 161.3, 137.9, 137.2, 135.1, 133.1, 130.9,
130.4, 130.2, 129.2, 128.2, 126.9, 125.8, 124.5, 123.8, 122.9,
122.8, 120.1, 119.9, 119.2, 62.7, 61.3, 42.6, 28.1, 19.9, 19.4,
1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-dicarboxylate
(9z): Reddish yellow solid (76%), mp. 202 ºC (EtOAc); IR (KBr,
1
υ cm-1): 2971, 1712, 1589, 1321, 1054, 868; H NMR (300 MHz,
CDCl3): δ 8.50-8.47 (m, 1H, Ar-H), 8.08-8.03 (m, 1H, Ar-H),
50 14.2, 14.0; Anal. calcd. for C32H29BrN2O5; C: 63.90; H: 4.86; N: 105 7.51-7.46 (m, 2H, Ar-H), 7.33 (d, J = 8.4 Hz, 2H, Ar-H), 6.97 (d,
4.66. Found: C: 63.87; H: 4.87; N: 4.60.
J = 9 Hz, 2H, Ar-H), 5.67 (s, 1H, vinylic-H), 4.50 (q, J = 6.9 Hz,
2H, -OCH2), 4.33 (q, J = 6.9 Hz, 2H, -OCH2), 3.80 (s, 3H, -
OCH3), 1.62 (s, 6H, -CH3), 1.40 (t, J = 7.2 Hz, 3H, -CH3), 1.34
(t, J = 7.2 Hz, 3H, -CH3); 13C NMR (75 MHz, CDCl3): δ 166.5,
110 163.1, 162.8, 160.3, 136.0, 134.1, 133.3, 132.6, 132.3, 130.9,
129.9, 128.5, 126.6, 125.8, 124.2, 123.3, 121.5, 119.1, 119.0,
Diethyl-9-chloro-2-(3,4-dimethylphenyl)-4,4-dimethyl-1-oxo-
2,4-dihydro-1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-
dicarboxylate (9w): Orange solid (70%), mp. 238 ºC (EtOAc);
55 IR (KBr, υ cm-1): 2987, 1707, 1565, 1197, 1045, 857; H NMR
1

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DOI: 10.1039/C5GC00156K
118.3, 117.6, 113.8, 108.0, 62.8, 61.6, 55.5, 41.1, 31.0, 14.1,
13.9; Anal. calcd. for C31H28N2O6; C: 70.98; H: 5.38; N: 5.34.
Found: C: 71.00; H: 5.41; N: 5.30.
C30H25BrN2O5; C: 62.84; H: 4.39; N: 4.89. Found: C: 62.82; H:
4.36; N: 4.93.
Diethyl-4,4-dimethyl-2-naphthalen-1-yl-1-oxo-2,4-dihydro-
1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-dicarboxylate
60 (9e’): Reddish yellow solid (74%), mp. 282 ºC (EtOAc); IR
Diethyl-9-bromo-2-(4-methoxyphenyl)-4,4-dimethyl-1-oxo-
2,4-dihydro-1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-
dicarboxylate (9a’): Reddish yellow solid (74%), mp. 218 ºC
(EtOAc); IR (KBr, υ cm-1): 2984, 1709, 1535, 1405, 1143, 980,
764; 1H NMR (300 MHz, CDCl3): δ 8.47 (d, J = 2.4 Hz, 1H, Ar-
H), 7.86 (d, J = 9 Hz, 1H, Ar-H), 7.48 (d, J = 6.9 Hz, 1H, Ar-H),
5
1
(KBr, υ cm-1): 2969, 1705, 1577, 1385, 1051, 927; H NMR (300
MHz, CDCl3): δ 8.51 (dd, J = 6 Hz, J = 3.3 Hz, 1H, Ar-H), 8.06
(dd, J = 6.3 Hz, J = 3.3 Hz, 1H, Ar-H), 7.96 (d, J = 7.8 Hz, 1H,
Ar-H), 7.76 (d, J = 8.1 Hz, 1H, Ar-H), 7.64-7.46 (m, 6H, Ar-H),
10 7.32 (d, J = 8.7 Hz, 2H, Ar-H), 6.94 (m, 2H, Ar-H), 5.66 (s, 1H, 65 5.37 (s, 1H, vinylic-H), 4.60 (q, J = 7.2 Hz, 2H, -OCH2), 4.41 (q,
vinylic-H), 4.48 (q, J = 7.2 Hz, 2H, -OCH2), 4.33 (q, J = 7.2 Hz,
2H, -OCH2), 3.78(s, 3H, -OCH3), 1.59 (s, 6H, -CH3), 1.42-1.32
(m, 6H, -CH3); 13C NMR (75 MHz, CDCl3): δ 166.9, 163.9,
163.4, 158.4, 132.9, 132.0, 131.1, 130.1, 128.6, 128.2, 127.7,
J = 7.2 Hz, 2H, -OCH2), 1.62 (s, 3H, -CH3), 1.60 (s, 3H, -CH3),
1.52(t, J = 7.2 Hz, 3H, -CH3), 1.42 (t, J = 7.2 Hz, 3H, -CH3); 13
NMR (75 MHz, CDCl3): δ 168.0, 164.0, 163.8, 134.7, 134.2,
C
132.2, 132.0, 131.9, 130.6, 128.9, 128.4, 127.4, 126.7, 126.7,
15 127.6, 127.0, 125.9, 124.5, 124.4, 123.6, 122.6, 120.6, 119.9, 70 126.5, 126.4, 126.4, 126.1, 125.7, 125.6, 124.5, 123.3, 123.0,
119.2, 114.6, 114.6, 107.2, 62.7, 61.2, 55.5, 42.6, 30.8, 28.0;
Anal. calcd. for C31H27BrN2O6; C: 61.70; H: 4.51; N: 4.64.
Found: C: 61.66; H: 4.47; N: 4.69.
122.4, 119.9, 117.7, 108.1, 62.6, 61.1, 42.6, 28.0, 27.9, 14.2,
14.0; Anal. calcd. for C34H28N2O5; C: 74.98; H: 5.18; N: 5.14.
Found: C: 75.03; H: 5.16; N: 5.12.
Diethyl-2-(4-chlorophenyl)-4,4-dimethyl-1-oxo-2,4-dihydro-
20 1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-dicarboxylate
(9b’): Yellow solid (68%), mp. 222 ºC (EtOAc); IR (KBr, υ cm-
Diethyl-2-benzyl-4,4-dimethyl-1-oxo-2,4-dihydro-1H-2,6a-
75 diazacyclopenta[fg]aceanthrylene-5,6-dicarboxylate
(10a):
Reddish yellow solid (73%), mp. 182 ºC (EtOAc); IR (KBr, υ cm-
1
1
1): 2970, 1710, 1544, 1413, 1201, 894, 755; H NMR (300 MHz,
1): 3003, 1712, 1610, 1489, 1154, 988, 745; H NMR (300 MHz,
CDCl3): δ 8.48-8.46 (m, 1H, Ar-H), 8.01-7.99 (m, 1H, Ar-H),
7.51-7.49 (m, 6H, Ar-H), 5.79 (s, 1H, vinylic-H), 4.59 (q, J = 6.9
CDCl3): δ 8.43-8.41 (m, 1H, Ar-H), 8.02-7.98 (m, 1H, Ar-H),
7.46-7.43 (m, 2H, Ar-H), 7.32-7.31 (m, 4H, Ar-H), 7.28-7.22 (m,
25 Hz, 2H, -OCH2), 4.42 (q, J = 6.9 Hz, 2H, -OCH2), 1.69 (s, 6H, - 80 1H, Ar-H), 5.50 (s, 1H, vinylic-H), 4.97 (s, 2H, -CH2), 4.57 (q, J
CH3), 1.52-1.41 (m, 6H, -CH3); 13C NMR (75 MHz, CDCl3): δ
167.1, 163.9, 134.4, 134.1, 132.2, 131.8, 130.6, 129.5, 127.6,
126.7, 126.4, 123.4, 122.7, 122.5, 119.7, 117.6, 107.8, 62.8, 61.2,
42.7, 28.1, 14.2, 14.0; Anal. calcd. for C30H25ClN2O5; C: 68.12;
30 H: 4.76; N: 5.30. Found: C: 68.05; H: 4.80; N: 5.27.
= 7.2 Hz, 2H, -OCH2), 4.40 (q, J = 7.2 Hz, 2H, -OCH2), 1.61 (s,
6H, -CH3), 1.47 (t, J = 7.2 Hz, 3H, -CH3), 1.41 (t, J = 7.2 Hz, 3H,
-CH3); 13C NMR (75 MHz, CDCl3): δ 168.2, 164.1, 163.8, 137.3,
134.0, 131.5, 130.7, 128.6, 128.6, 127.4, 127.2, 126.2, 125.7,
85 124.6, 122.9, 121.8, 119.9, 117.7, 108.3, 62.6, 61.1, 44.2, 42.4,
28.0, 14.2, 14.0; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
[C31H28N2O5Na]: 531.1890. Found 531.1799. Anal. calcd. for
C31H28N2O5; C: 73.21; H: 5.55; N: 5.51. Found: C: 73.27; H:
5.54; N: 5.49.
Diethyl-9-bromo-2-(4-chlorophenyl)-4,4-dimethyl-1-oxo-2,4-
dihydro-1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-
dicarboxylate (9c’): Yellow solid (67%), mp. 218 ºC (EtOAc);
1
IR (KBr, υ cm-1): 2983, 1703, 1604, 1364, 1214, 897; H NMR
35 (300 MHz, CDCl3): δ 8.58 (d, J = 2.1 Hz, 1H, Ar-H), 7.94 (d, J = 90 Diethyl-2-benzyl-9-bromo-4,4-dimethyl-1-oxo-2,4-dihydro-
9 Hz, 1H, Ar-H), 7.59 (d, J = 9.3 Hz, 1H, Ar-H), 7.48-7.41 (m,
4H, Ar-H), 5.81 (s, 1H, vinylic-H), 4.57 (q, J = 7.2 Hz, 2H, -
OCH2), 4.42 (q, J = 7.2 Hz, 2H, -OCH2), 1.68 (s, 6H, -CH3),
1.51-1.41 (m, 6H, -CH3); 13C NMR (75 MHz, CDCl3): δ 166.5,
1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-dicarboxylate
(10b): Reddish yellow solid (70%), mp. 210-212 ºC (EtOAc); IR
1
(KBr, υ cm-1): 2979, 1709, 1541, 1488, 1161, 931, 832; H NMR
(300 MHz, CDCl3): δ 8.32-8.28 (m, 1H, Ar-H), 7.90-7.87 (m, 1H,
40 163.8, 163.5, 134.2, 133.0, 132.4, 130.4, 129.5, 128.8, 126.6, 95 Ar-H), 7.38-7.29 (m, 3H, Ar-H), 6.95-6.90 (m, 3H, Ar-H), 5.62
124.3, 123.8, 123.1, 120.5, 120.2, 119.2, 107.0, 62.8, 61.3, 42.8,
28.1, 14.2, 14.0; Anal. calcd. for C30H24BrClN2O5; C: 59.28; H:
3.98; N: 4.61. Found: C: 59.33; H: 3.95; N: 4.62.
(s, 1H, vinylic-H), 4.48 (q, J = 7.2 Hz, 2H, -OCH2), 4.31 (q, J =
7.2 Hz, 2H, -OCH2), 3.74 (s, 2H, -CH2), 1.58 (s, 6H, -CH3), 1.39
(t, J = 7.2 Hz, 3H, -CH3), 1.32 (t, J = 7.2 Hz, 3H, -CH3); 13C
NMR (75 MHz, CDCl3): δ 166.9, 164.0, 163.8, 158.3, 134.0,
100 131.4, 131.3, 129.4, 128.5, 127.6, 127.4, 127.1, 126.2, 126.0,
124.5, 124.2, 123.2, 122.8, 122.6, 121.6, 119.8, 117.6, 114.5,
108.0, 62.7, 61.1, 55.5, 42.5, 28.1, 14.2, 14.0; Anal. calcd. for
C31H27BrN2O5; C: 63.38; H: 4.63; N: 4.77. Found: C: 63.40; H:
4.61; N: 4.72.
Diethyl-2-(4-bromophenyl)-4,4-dimethyl-1-oxo-2,4-dihydro-
45 1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-dicarboxylate
(9d’): Yellow solid (68%), mp. 231 ºC (EtOAc); IR (KBr, υ cm-
1): 2962, 1702, 1591, 1352, 1144, 1021, 902; 1H NMR (300 MHz,
CDCl3): δ 8.12-8.08 (m, 1H, Ar-H), 7.71-7.68 (m, 1H, Ar-H),
7.36-7.33 (m, 2H, Ar-H), 7.22-7.13 (m, 4H, Ar-H), 5.54 (s, 1H,
50 vinylic-H), 4.30 (q, J = 7.2 Hz, 2H, -OCH2), 4.13 (q, J = 7.2 Hz, 105 Dimethyl-2-benzyl-9-bromo-4,4-dimethyl-1-oxo-2,4-dihydro-
2H, -OCH2), 1.41 (s, 6H, -CH3), 1.21(t, J = 7.2 Hz, 3H, -CH3),
1.15 (t, J = 7.2 Hz, 3H, -CH3); 13C NMR (75 MHz, CDCl3): δ
166.3, 163.3, 163.1, 134.4, 133.4, 131.8, 131.2, 129.8, 127.1,
126.5, 125.8, 123.7, 122.9, 122.1, 122.0, 119.4, 119.2, 117.1,
1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-dicarboxylate
(10c): Reddish yellow solid (70%), mp. 221 ºC (EtOAc); IR
(KBr, υ cm-1): 2968, 1708, 1495, 1397, 1213, 935; 1H NMR (300
MHz, CDCl3): δ 8.38 (d, J = 2.1 Hz, 1H, Ar-H), 8.19 (d, J = 9.6
55 107.1, 62.2, 60.6, 42.1, 27.5, 13.7, 13.4; Anal. calcd. for 110 Hz, 1H, Ar-H), 7.57 (d, J = 8.7 Hz, 1H, Ar-H), 7.43 (dd, J = 8.7

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DOI: 10.1039/C5GC00156K
Hz, J = 2.1 Hz, 1H, Ar-H), 7.24-7.18 (m, 4H, Ar-H), 5.44 (s, 1H,
vinylic-H), 4.86 (s, 2H, -CH2), 3.83 (s, 3H, -OCH3), 3.79 (s, 3H, -
OCH3), 1.54 (s, 6H, -CH3); 13C NMR (75 MHz, CDCl3): δ 168.1,
164.4, 137.2, 133.1, 132.0, 130.5, 129.8, 128.7, 128.6, 127.5,
1H, vinylic-H), 4.46 (q, J = 7.2 Hz, 2H, -OCH2), 4.33 (q, J = 7.2
Hz, 2H, -OCH2), 3.69 (t, J = 6.9 Hz, 2H, -NCH3), 1.59 (s, 6H, -
CH3), 1.38-1.28 (m, 6H, -CH3), 1.19-1.15 (m, 4H, -CH2), 0.93-
0.88 (m, 3H, -CH3); 13C NMR (75 MHz, CDCl3): δ 167.7, 164.0,
5
127.5, 124.5, 124.0, 123.9, 122.9, 120.5, 119.4, 118.5, 117.0, 60 163.4, 132.9, 131.8, 130.8, 129.9, 128.5, 125.5, 124.6, 124.6,
115.6, 51.5, 44.2, 43.0, 27.6; Anal. calcd. for C29H23BrN2O5; C:
62.26; H: 4.14; N: 5.01. Found: C: 62.30; H: 4.15; N: 4.98.
123.0, 121.4, 120.7, 119.8, 119.2, 107.8, 62.6, 61.2, 42.4, 40.2,
31.1, 28.1, 20.1, 14.0, 13.9, 13.8; Anal. calcd. for C28H29BrN2O5;
C: 60.76; H: 5.28; N: 5.06. Found: C: 60.83; H: 5.27; N: 4.02.
Dimethyl-4,4-dimethyl-2-(4-methylbenzyl)-1-oxo-2,4-dihydro-
1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-dicarboxylate
Diethyl-2-cyclohexyl-4,4-dimethyl-1-oxo-2,4-dihydro-1H-2,6a-
10 (10d): Reddish yellow solid (75%), mp. 205-206 ºC (EtOAc); IR 65 diazacyclopenta[fg]aceanthrylene-5,6-dicarboxylate
(10h):
(KBr, υ cm-1): 2955, 1711, 1588, 1373, 1291, 1044, 833; 1H
NMR (300 MHz, CDCl3): δ 8.32-8.28 (m, 1H, Ar-H), 7.82-7.79
(m, 1H, Ar-H), 7.42-7.39 (m, 2H, Ar-H), 7.14-7.11 (m, 4H, Ar-
H), 5.42 (s, 1H, vinylic-H), 4.86 (s, 2H, -CH2), 4.02 (s, 3H, -
Yellow solid (68%), mp. 213-214 ºC (EtOAc); IR (KBr, υ cm-1):
3012, 1715, 1608, 1364, 1199, 1014, 833, 742; 1H NMR (300
MHz, CDCl3): δ 8.70 (d, J = 6.6 Hz, 1H, Ar-H), 8.12 (d, J = 7.8
Hz, 1H, Ar-H), 7.87-7.72 (m, 2H, Ar-H), 5.90 (s, 1H, vinylic-H),
15 OCH3), 3.87 (s, 3H, -OCH3), 2.28 (s, 3H, -CH3), 1.50 (s, 6H, - 70 4.84-4.25 (m, 4H, -OCH2), 4.04-3.99 (m, 1H, -NCH), 2.13-1.99
CH3); 13C NMR (75 MHz, CDCl3): δ 164.0, 162.0, 161.7, 137.1,
134.0, 134.0, 131.9, 131.1, 129.5, 129.3, 129.1, 128.3, 128.1,
127.5, 127.2, 126.4, 126.0, 123.0, 122.8, 122.0, 120.3, 115.6,
55.2, 53.3, 52.8, 44.0, 29.7, 21.1; Anal. calcd. for C30H26N2O5; C:
20 72.86; H: 5.30; N: 5.66. Found: C: 72.81; H: 5.34; N: 5.69.
(m, 6H, -CH2), 1.86-1.79 (m, 4H, -CH2), 1.55 (s, 6H, -CH3), 1.52-
1.42 (m, 6H, -CH3); 13C NMR (75 MHz, CDCl3): δ 167.2, 166.3,
154.3, 142.7, 131.8, 130.9, 130.5, 129.8, 129.3, 128.7, 127.5,
124.8, 124.0, 122.6, 117.7, 60.8, 60.4, 48.8, 42.8, 37.1, 31.0,
75 27.8, 25.4, 13.3, 13.1; Anal. calcd. for C30H32N2O5; C: 71.98; H:
6.44; N: 5.60. Found: C: 71.91; H: 6.41; N: 5.56.
Dimethyl-9-bromo-4,4-dimethyl-2-(4-methylbenzyl)-1-oxo-
2,4-dihydro-1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-
dicarboxylate (10e): Reddish yellow solid (72%), mp. 233 ºC
(EtOAc); IR (KBr, υ cm-1): 2955, 1711, 1588, 1373, 1291, 1044,
Diethyl-9-bromo-2-cyclohexyl-4,4-dimethyl-1-oxo-2,4-
dihydro-1H-2,6a-diazacyclopenta[fg]aceanthrylene-5,6-
dicarboxylate (10i): Yellow solid (67%), mp. 232 ºC (EtOAc);
25 833; 1H NMR (300 MHz, CDCl3): δ 8.52 (d, J = 2.4 Hz, 1H, Ar- 80 IR (KBr, υ cm-1): 3004, 1713, 1622, 1444, 1249, 1135, 952, 743;
H), 7.86 (d, J = 9.3 Hz, 1H, Ar-H), 7.48 (dd, J = 9.3 Hz, J = 2.4
Hz, 1H, Ar-H), 7.07-7.01(m, 4H, Ar-H), 5.46 (s, 1H, vinylic-H),
4.85 (s, 2H, -CH2), 4.00 (s, 3H, -OCH3), 3.85 (s, 3H, -OCH3),
2.24 (s, 3H, -CH3), 1.50 (s, 6H, -CH3); 13C NMR (75 MHz,
1H NMR (300 MHz, CDCl3): δ 8.52 (d, J = 2.4 Hz, 1H, Ar-H),
8.26 (d, J = 9 Hz, 1H, Ar-H), 7.86 (d, J = 9 Hz, 1H, Ar-H), 5.86
(s, 1H, vinylic-H), 4.47 (q, J = 7.2 Hz, 2H, -OCH2), 4.34 (q, J =
7.2 Hz, 2H, -OCH2), 4.22-4.18 (m, 1H, -NCH), 1.87-1.84 (m,
30 CDCl3): δ 167.6, 164.4, 163.9, 137.2, 134.0, 132.8, 132.0, 130.5, 85 6H, -CH2), 1.73 (s, 4H, -CH2), 1.53 (s, 6H, -CH3), 1.43-1.33 (m,
130.1, 129.5, 129.4, 129.3, 129.2, 128.7, 128.3, 127.4, 126.3,
125.2, 124.6, 123.4, 122.3, 120.5, 120.0, 119.2, 53.3, 52.1, 44.0,
42.4, 28.0, 21.0; Anal. calcd. for C30H25BrN2O5; C: 62.84; H:
4.39; N: 4.89. Found: C: 62.88; H: 4.36; N: 4.91.
6H, -CH3); 13C NMR (75 MHz, CDCl3): δ 167.2, 166.3, 154.3,
142.7, 134.3, 133.5, 129.9, 126.4, 123.4, 119.1, 118.4, 62.7, 61.2,
48.9, 42.5, 31.9, 29.7, 26.4, 25.4, 14.2, 14.1, 14.0; Anal. calcd.
for C30H31BrN2O5; C: 62.18; H: 5.39; N: 4.83. Found: C: 62.11;
90 H: 5.37; N: 4.86.
35 Diethyl-2-butyl-4,4-dimethyl-1-oxo-2,4-dihydro-1H-2,6a-
diazacyclopenta[fg]aceanthrylene-5,6-dicarboxylate
(10f):
4,4-Dimethyl-2-p-tolyl-4,5-dihydro-2H-pyrrolo[2,3,4-
Yellow solid (74%), mp. 170-171 ºC (EtOAc); IR (KBr, υ cm-1):
kl]acridin-1-one (Intermediate D of 9a):Light yellow solid; m.p.
223 °C (EtOAc); IR (KBr, υ cm-1): 3075, 2957, 1719, 1466,
1
2999, 1713, 1598, 1503, 1355, 1260, 1044, 865, 735; H NMR
(300 MHz, CDCl3): δ 8.39-8.36 (m, 1H, Ar-H), 7.95-7.93 (m, 1H,
1
1354, 1141, 837, 732, 479; H NMR (300 MHz, CDCl3): δ 8.73
40 Ar-H), 7.42-7.39 (m, 2H, Ar-H), 5.54 (s, 1H, vinylic-H), 4.50 (q, 95 (d, J = 7.8 Hz, 1H, Ar-H), 8.17 (d, J = 8.4 Hz, 1H, Ar-H), 7.78-
J = 6.9 Hz, 2H, -OCH2), 4.34 (q, J = 6.9 Hz, 2H, -OCH2), 3.37-
3.69 (m, 2H, -NCH2), 1.53 (s, 6H, -CH3), 1.43-1.34 (m, 6H, -
CH3), 1.19 (t, J = 7.2 Hz, 2H, -CH2), 0.93-0.88 (m, 3H, -CH3);
13C NMR (75 MHz, CDCl3): δ 168.2, 164.2, 163.9, 134.1, 133.0,
7.72 (m, 1H, Ar-H), 7.68-7.63 (m, 1H, Ar-H), 7.40-7.33 (m, 4H,
Ar-H), 5.59 (s, 1H, vinylic-H), 3.21 (s, 2H, -CH2), 2.44 (s, 3H, -
CH3), 1.32 (s, 6H, -CH3); 13C NMR (75 MHz, CDCl3): δ 166.8,
154.6, 149.7, 137.4, 133.6, 132.1, 130.0, 129.9, 129.4, 127.7,
45 131.1, 130.0, 127.2, 126.4, 126.2, 125.5, 123.0, 122.4, 120.8, 100 126.4, 126.4, 126.3, 126.2, 125.1, 124.3, 122.6, 118.1, 44.2, 37.0,
117.7, 62.6, 61.1, 42.4, 40.3, 31.2, 28.2, 20.2, 14.2, 14.0, 13.8;
HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for [C28H30N2O5Na]:
497.2047. Found 497.2068. Anal. calcd. for C28H30N2O5; C:
70.87; H: 6.37; N: 5.90. Found: C: 70.81; H: 6.41; N: 5.88.
30.9, 21.2; Anal. Calcd for C23H20N2O: C, 81.15; H, 5.92; N,
8.23%. Found: C, 81.18; H, 5.93; N, 8.24%.
50 Diethyl-9-bromo-2-butyl-4,4-dimethyl-1-oxo-2,4-dihydro-1H-
2,6a-diazacyclopenta[fg]aceanthrylene-5,6-dicarboxylate
(10g): Yellow solid (72%), mp. 183 ºC (EtOAc); IR (KBr, υ cm-
Acknowledgements
105 One of the authors (PS) thanks the Council of Scientific &
Industrial Research, New Delhi for her fellowship (SRF). We
thank the CAS Instrument Facility, University of Calcutta for
spectral data.
1
1): 3005, 1711, 1662, 1505, 1288, 1054, 963, 750; H NMR (300
MHz, CDCl3): δ 8.46 (d, J = 1.8 Hz, 1H, Ar-H), 7.87 (d, J = 9
55 Hz, 1H, Ar-H), 7.45 (dd, J = 9 Hz, J = 2.1 Hz, 1H, Ar-H), 5.58 (s,

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DOI: 10.1039/C5GC00156K
Notes and references
a
Department of Chemistry, University of Calcutta, 92 APC Road,
Kolkata, 700009,
India.
Tel:
+91
9433019610; E-mail:
cmukhop@yahoo.co.in
5 † Electronic Supplementary Information (ESI) available: [CCDC
1014291. Details of supplementary information (experimental procedure,
spectral data and crystallographic data in CIF) available]. See
DOI: 10.1039/b000000x/
1
2
(a) P. Das, R. J. Butcher and C. Mukhopadhyay, Green Chem., 2012,
14, 1376–1387; (b) Y. Gu, Green Chem., 2012, 14, 2091–2128.
10
15
20
25
30
35
40
(a) S. Ray, A. Bhaumik, M. Pramanik and C. Mukhopadhyay, RSC
Adv., 2014, 4, 15441–15450; (b) S. Ray, P. Das, A. Bhaumik, A.
Dutta and C. Mukhopadhyay, Applied Catalysis A: General, 2013,
458,183– 195; (c) L. A. Joyce, S. H. Shabbir and E. V. Anslyn,
Chem. Soc. Rev., 2010, 39, 3621–3632; (d) M. North, R. Pasquale
and C. Young, Green Chem., 2010, 12, 1514–1539.
3
4
(a) M. Hatanoa and K. Ishihara, Chem. Commun., 2012, 48, 4273–
4283 (b) R. R. Knowles and E. Jacobsen, N. Proc Natl Acad Sci U S
A., 2010, 107, 20678-20685; (b) B. Escuder, F. Rodrı´guez-Llansola
and J. F. Miravet, New J. Chem., 2010, 34, 1044–1054.
(a) P. Sarkar, S. Maiti, K. Ghosh, S. Sengupta (Bandyopadhyay), R.
J. Butcher and C. Mukhopadhyay, Tetrahedron Letters, 2014, 55,
996–1001; (b) S. Shimizu, N. Shimada and Y. Sasaki, Green Chem.,
2006, 8, 608–614; (c) J. B. Simoes, A. d. Fatima, A. A. Sabino, L. C.
A. Barbosa and S. A. Fernandes, RSC Adv., 2014, 4, 18612–18615.
5
6
(a) S. Pasquale, S. Sattin, E. C. Escudero-Adán, M. Martínez-
Belmonte and J. d. Mendoza, Nature Communications | 3:785 | DOI:
10.1038/ncomms1793, 2012; (b) L. K. Tsou, G. E. Dutschman, E. A.
Gullen, M. Telpoukhovskaia, Y.C. Cheng and A. D. Hamilton,
Bioorg. Med. Chem. Lett., 2010, 20, 2137–2139.
(a) L. Moni, S. Rossetti, M. Scoponi, A. Marra and A. Dondoni,
Chem. Commun., 2010, 46, 475–477; (b) C. Lynam, K. Jennings, K.
Nolan, P. Kane, M. A. McKervey and D. Diamond, Anal. Chem.,
2002, 74, 59-66; (c) A. Casnati, Y. Ting, D. Berti, M. Fabbi, A.
Pochini, R. Ungaro, D. Sciotto and G. G. Lombardo, Tetrahedron,
1993, 49, 9815-9822.
7
8
(a) P. Kovacic1, R. Somanathan, Open Journal of Preventive
Medicine, 2014, 4, 583-597; (b) P. Ralifo, L. Sanchez, N. C. Gassner,
K. Tenney, R. S. Lokey, T.R. Holman, F. A. Valeriote and P. Crews,
J Nat Prod., 2007; 70, 95–99; (c) D. J. Newman and G. M. Cragg, J.
Nat. Prod., 2004, 67, 1216-1238.
Z. Thale, T. Johnson, K. Tenney, P. J. Wenzel, E. Lobkovsky, J.
Clardy, J. Media, H. Pietraszkiewicz, F. A. Valeriote and P. Crews,
J. Org. Chem., 2002, 67, 9384-9391.
45 9 (a) G. P. Gunawardana, F. E. Koehn, A. Y. Lee, J. Clardy, H. He and
D. J. Faulkner, J. Org. Chem., 1992, 57, 1523-1526; (b) P. W. Ford
and B. S. Davidson, J. Nat. Prod., 1997, 60, 1051-1053; (c) G. P.
Gunawardand, S. Kohmoto and N. S. Burres, Tetrahedron Letters,
1989, 30, 4359-4362.
50 10 B. Jiang, X. Wang, H. W. Xu, M. S. Tu, S. J. Tu and G. Li, Org.
Lett., 2013, 15, 1540–1543.
11 C. Fischer, W. Seichter and E. Weber, Beilstein J. Org. Chem., 2011,
7, 1602–1608.
12 X. Cai, Y. Wu, L. Wang, N. Yan, J. Liu, X. Fanga and Y. Fang, Soft
55
Matter, 2013, 9, 5807-5814.