Efficient one-pot multicomponent synthesis of (carbazolylamino)furan-2(5 H)-one and carbazolyltetrahydropyrimidine derivatives

Article abstract of DOI:10.1055/s-0030-1260135

A simple and efficient approach to the synthesis of (carbazolylamino)furan- 2(5H)-one derivatives by the three-component reaction of 3-aminocarbazoles, dialkyl acetylenedicarboxylates and aromatic/heterocyclic aldehydes was developed. Further, we describe

Full text of DOI:10.1055/s-0030-1260135

PAPER
3307
Efficient One-Pot Multicomponent Synthesis of (Carbazolylamino)furan-
2(5H)-one and Carbazolyltetrahydropyrimidine Derivatives
M
ulticompone
u
nt Synthesis
b
of
H
eteroary
b
l-Substituted
u
C
arbazolesrethinam Ramesh, Rajagopal Nagarajan*
School of Chemistry, University of Hyderabad, Hyderabad 500 046, India
Fax +91(40)23012460; E-mail: rnsc@uohyd.ernet.in
Received 29 April 2011; revised 6 July 2011
R1
N
Br
H
N
Abstract: A simple and efficient approach to the synthesis of (car-
bazolylamino)furan-2(5H)-one derivatives by the three-component
reaction of 3-aminocarbazoles, dialkyl acetylenedicarboxylates and
aromatic/heterocyclic aldehydes was developed. Further, we de-
scribe an ionic liquid mediated, one-pot three-component strategy
to synthesize carbazolyltetrahydropyrimidine derivatives from 3-
aminocarbazoles, formaldehyde and dialkyl acetylenedicarboxy-
lates.
HN
HN
N
HN
O
Br
COOH
O
R3
N
(–)-manzacidin C
R2
aplicyanins A–F
A: R1 = R2 = R3 = H
B: R1 = Ac, R2 = R3 = H
C: R1 = R3 = H, R2 = OMe
Key words: multicomponent reactions, furan-2(5H)-ones, tetrahy-
dropyrimidines, heteroarylcarbazoles, ionic liquids
D: R1 = Ac, R2 = OMe, R3 = H
E: R1 = H, R2 = OMe, R3 = Br
F: R1 = Ac, R2 = OMe, R3 = Br .
Multicomponent reactions (MCRs) are one of the current
important areas of modern synthetic organic chemistry.1
MCRs have been becoming a powerful tool for simple and
convergent paths to synthesize structurally complex prod-
ucts from simple starting materials in a one-pot fashion.
The MCR strategies demonstrate a broad scope of appli-
cations for the synthesis of a variety of natural products.2
O
OH
O
O
(S)
O
OAc
O
O
acetylmelodorinol
fugomycin
HO
In recent years, furan-2(5H)-ones3 have attracted consid-
erable attention as they are found in a large number of
biologically active natural products (Figure 1).4 These
products exhibit diverse biological activities, such as anti-
fungal,5 antioxidant,6 anti-inflammatory,6 cytotoxic and
antiproliferative activity (against colon cancer, pancreatic
carcinoma, prostatic cancer and human lung cancer), and
also some other activities.7
O
O
tetrenolin
HO
Figure 1 Some biologically active furanones and tetrahydropyri-
midines
Tetrahydropyrimidines8 represent one of the most impor-
tant classes of heterocycles that have gained attention due
to their broad biological activities. Several tetrahydropy-
rimidine derivatives exhibit muscarinic agonist activi-
ty.8q,r Biologically active heterocycles such as pyridone,
iminopyridines and thiazolidinones incorporated with the
tetrahydropyrimidine moiety have shown strong antimi-
crobial activity.9 Aplicyanins A–F (Figure 1), a new fam-
ily of tetrahydropyrimidine-based indole alkaloids, have
cytotoxic, antiproliferative and antimitotic activities.10
synthesis of heteroarylcarbazoles,13 we have now extend-
ed our methodology to new furanone- and tetrahydropyri-
midine-substituted carbazole derivatives.
Initially, p-nitrobenzaldehyde (1a), diethyl acetylenedi-
carboxylate (2a) and 9-ethyl-9H-carbazol-3-amine (3a)
were stirred in acetonitrile as solvent at room temperature
to establish the feasibility of the strategy, and we obtained
ethyl 4-(9-ethyl-9H-carbazol-3-ylamino)-2-(4-nitrophe-
nyl)-5-oxo-2,5-dihydro-3-furancarboxylate (4a) in a trace
amount (Table 1, entry 1). Encouraged by this interesting
result, we continued to focus on the optimization of the re-
action conditions. The choice of a reaction medium is of
great importance for a successful synthesis. As shown in
Table 1, the optimization for the reaction was performed
on various parameters, such as temperature, base, concen-
tration of base and solvent. Various bases (Et3N, Na2CO3,
K2CO3, KOH) were screened for their efficiency in the re-
action. Among them, potassium hydroxide was proven su-
perior to the other bases (Table 1, entry 5; 75%); when the
Numerous compounds with a carbazole nucleus have
been shown to possess a wide range of pharmacological
properties.11 Considering the few reports on heteroaryl-
substituted carbazoles,12–14 the development of new and
simple synthetic methods for this kind of compound is an
interesting challenge. In continuation of our work on the
SYNTHESIS 2011, No. 20, pp 3307–3317
x
x.
x
x
.
2
0
1
1
Advanced online publication: 15.09.2011
DOI: 10.1055/s-0030-1260135; Art ID: N45411SS
© Georg Thieme Verlag Stuttgart · New York

3308
S. Ramesh, R. Nagarajan
PAPER
chosen as the reaction temperature for all further studies
on the synthesis of such furan-2(5H)-one derivatives. Un-
der the optimized conditions, the scope of this three-com-
ponent reaction was examined with a series of aldehydes
1a–o (aromatic, heterocyclic), dialkyl acetylenedicarbox-
ylates 2a, 2b, and 9-alkyl-9H-carbazol-3-amines 3a–e
(Table 2). The benzaldehydes with electron-withdrawing
groups (such as F, Cl, Br, NO2) or electron-donating
groups (such as Me, OMe), as well as the heterocyclic al-
dehydes (such as carbazole, quinoline and pyrazole deriv-
atives) with similar substituents, gave the corresponding
(carbazolylamino)furan-2(5H)-ones 4a–t in good yields.
Table 1 Optimization of the Reaction Conditions for the Synthesis
of (Carbazolylamino)furan-2(5H)-one 4aa
O2N
NH2
CHO
O
COOEt
O
base
+
+
COOEt
2a
EtOOC
solvent, r.t.
NH
N
Et
NO2
1a
3a
N
4a
Et
Entry Baseb
Solvent
Time
(min)
Yieldc
(%)
Unfortunately, aliphatic aldehydes (such as propanal and
valeraldehyde) did not tolerate the reaction. This may be
due to the lesser reactivity of aliphatic aldehydes. The X-
ray crystal structure of 4a is represented in Figure 2.15 The
proposed mechanism for the formation of 4a is shown in
Scheme 1.
1
2
–
MeCN
MeCN
MeCN
MeCN
MeCN
CH2Cl2
THF
60
40
40
30
30
30
30
30
30
trace
30
35
45
75
50
70
65
70
90
90
65
75
90
Na2CO3 (1 equiv)
K2CO3 (1 equiv)
Et3N (1 equiv)
KOH (1 equiv)
KOH (1 equiv)
KOH (1 equiv)
KOH (1 equiv)
KOH (1 equiv)
KOH (1 equiv)
KOH (2 equiv)
KOH (1 equiv)
KOH (0.5 equiv)
KOH (1 equiv)
3
4
5
6
7
8
EtOH
9
MeOH
10
11
12
13
14d
MeCN–H2O (9:1) 30
MeCN–H2O (9:1)
MeCN–H2O (1:1)
MeCN–H2O (9:1)
MeCN–H2O (9:1)
30
30
30
30
a For entries 1–13, room temperature was maintained.
b In all entries, the base equivalent was calculated relative to the mol%
of 3-aminocarbazole 3a.
c Yield refers to column-purified product.
d Reaction was carried out at 60 °C, followed by reflux temperature of
acetonitrile.
Figure 2 Crystal structure of 4a
reaction was carried out without any added base, the yield
was very low (Table 1, entry 1). Further, the reaction was
performed in different solvent systems (MeCN, CH2Cl2,
THF, EtOH, MeOH) at room temperature with 1 equiva-
lent of potassium hydroxide (Table 1, entries 5–9). Under
similar conditions, the yield increased to 90% when a
mixture of acetonitrile and water (9:1) was used (Table 1,
entry 10).
In our next experiment, the MCR strategy was focused on
the synthesis of carbazolyltetrahydropyrimidine deriva-
tives 6a–j using 3-aminocarbazoles 3a–e, acetylenes 2a–
c and formaldehyde (5). In order to synthesize the tetrahy-
dropyrimidine attached to two carbazole units, we started
the optimization with 2 equivalents of 9-ethyl-9H-carba-
zol-3-amine (3a), 1.2 equivalents of diethyl acetylenedi-
carboxylate (2a) and 6 equivalents of 37% formaldehyde
solution (5) at room temperature with 1 equivalent of po-
tassium hydroxide as base and acetonitrile as solvent.
When the reaction was performed at 50 °C, 60 °C and
80 °C, the yield was 20%, 35% and 40%, respectively. We
observed that temperature is an important parameter for
this conversion. Thus, we focused on high-boiling sol-
vents such as N,N-dimethylformamide, dimethyl sulfox-
Increasing the base concentration did not lead to any im-
provement in the reaction yield or in the reaction time
(Table 1, entry 11). The yield of the product 4a was found
to decrease as the concentration of the base was decreased
from 1 equivalent to 0.5 equivalents (Table 1, entry 13;
75%). No significant improvement in yield was obtained
when the reaction temperature was increased to 60 °C,
followed by the reflux temperature of acetonitrile
(Table 1, entry 14). Therefore, room temperature was
Synthesis 2011, No. 20, 3307–3317 © Thieme Stuttgart · New York

PAPER
Multicomponent Synthesis of Heteroaryl-Substituted Carbazoles
3309
Table 2 Synthesis of (Carbazolylamino)furan-2(5H)-one Derivatives 4a–ta
R1
R2
CHO
FG
O
COOR3
R5
NH2
R2
KOH
O
(1 equiv)
R3OOC
+
+
FG
MeCN–H2O
(9:1)
R5
NH
COOR3
N
R4
R1
r.t.
1a–o
3a–e
2a,b
N
R4
4a–t
CHO
Acetylenes
Aldehydes
CHO
2a: R3 = Et
OHC
O
O
1a: R1 = NO2, R2 = H
1b: R1 = F, R2 = H
1c: R1 = Cl, R2 = H
1d: R1 = Br, R2 = H
1e: R1 = R2 = H
2b: R3 = Me
1k
1l
1j
Aminocarbazoles
CHO
CHO
1f: R1 = Me, R2 = H
1g: R1 = OMe, R2 = H
1h: R1 = R2 = Cl
CHO
3a: R4 = Et, R5 = H
3b: R4 = Me, R5 = H
3c: R4 = Bn, R5 = H
3d: R4 = Et, R5 = Cl
3e: R4 = Et, R5 = Br
Cl
N
N
1i: R1 = H, R2 = Br
N
Cl
N
Et
1m
1n
1o
Entry
1
Aldehyde
1a
Amine
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3b
3c
Product
4a
4b
4c
Time (h)
Yield (%)
90
0.5
0.5
0.5
0.5
1.0
2.0
2.0
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
2
1b
1c
87
3
85
4
1d
1e
4d
4e
83
5
72
6
1f
4f
65
7
1g
4g
4h
4i
60
8
1h
1i
83
9
85
10
11
12
13
14
15
16
17
18
19
20
1j
4j
75
1k
1l
4k
4l
72
78
1m
1n
1o
4m
4n
4o
4p
4q
4r
85
80
70
1a
92
1a
90
1a
91
1a
3d
3e
4s
90
1a
4t
90
a For all entries except entry 16, acetylene 2a was used. For entry 16, acetylene 2b was used.
Synthesis 2011, No. 20, 3307–3317 © Thieme Stuttgart · New York

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S. Ramesh, R. Nagarajan
PAPER
Et
COOEt
H
O
O
EtOOC
NH2
EtOOC
COOEt
NH
H
N
+
a
b
_
N
COOEt
N
O
Et
N
3a
2a
Et
Et
Et
O2N
–
Et
O
O
O2N
O
O
O
H
O
O
H
O
EtOOC
Et
NH
EtOOC
N
O
N
NH
1a
NO2
N
N
4a
Et
Et
Et
a = hydroamination, b = KOH (1 equiv)
Scheme 1 Proposed mechanism for the formation of 4a
ide, toluene and ionic liquids. The yield remained mL) at 110 °C for 1 hour without any catalyst. With the
unaffected in the absence of added base. Prolonging the optimized conditions in hand, the scope of this three-com-
reaction time did not lead to an increased yield. From the ponent reaction was examined with a series of 3-ami-
optimization process, we found that the maximum yield nocarbazoles 3a–e, acetylenes 2a–c and formaldehyde (5)
(84%) of 6a was obtained in the ionic liquid 1-butyl-3- (Table 3).
methylimidazolium tetrafluoroborate ([Bmim][BF4], 3
Table 3 Synthesis of Carbazolyltetrahydropyrimidine Derivatives 6a–j
R3
R3
O
O
O
N
O
R5
R5
NH2
R5
COOR3
ionic liquid
110 °C, 1 h
N
+
+
HCHO
N
R4
3a–e
COOR3
N
R4
N
5
R4
6a–j
2a–c
Acetylenes
Ionic liquid
Aminocarbazoles
2a: R3 = Et
3a: R4 = Et, R5 = H
3b: R4 = Me, R5 = H
3c: R4 = Bn, R5 = H
3d: R4 = Et, R5 = Cl
3e: R4 = Et, R5 = Br
2b: R3 = Me
N
Bu
+
N
Me
–
BF4
2c:
EtOOC
H
Entry
Acetylene
Amine
Product
Yield (%)
1
2
2a
2b
2c
2a
2b
2a
2a
2b
2a
2b
3a
3a
3a
3b
3b
3c
3d
3d
3e
3e
6a
6b
6c
6d
6e
6f
84
88
75
85
82
80
83
85
85
82
3
4
5
6
7
6g
6h
6i
8
9
10
6j
Synthesis 2011, No. 20, 3307–3317 © Thieme Stuttgart · New York

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Multicomponent Synthesis of Heteroaryl-Substituted Carbazoles
3311
1
The proposed mechanism for the formation of 6a is shown The H NMR and 13C NMR spectra were recorded at 400 or 500
MHz and 100 or 125 MHz, respectively. The chemical shifts are re-
in Scheme 2. The X-ray crystal structure of 6b is repre-
ported in ppm downfield to TMS (d = 0 ppm) for 1H NMR and rel-
ative to the central CDCl3 resonance (d = 77.0 ppm) for 13C NMR.
In the 13C NMR spectra, the nature of the carbons (C, CH, CH2 or
CH3) was determined by recording the DEPT-135 experiment, and
is given in parentheses. The coupling constants J are given in Hz.
IR spectra were recorded on JASCO FT/IR-5300. Elemental analy-
ses were recorded on a Thermo Finnigan Flash EA 1112 analyzer.
Mass spectra were recorded on either a VG7070H mass spectrome-
ter using EI technique or a Shimadzu LCMS-2010 A mass spec-
trometer. The X-ray diffraction measurements were carried out at
298 K on an automated Enraf-Nonious MACH 3 diffractometer us-
ing graphite monochromated, Mo-Kα (l = 0.71073 Å) radiation
with CAD4 software or the X-ray intensity data were measured at
298 K on a Bruker SMART APEX CCD area detector system
equipped with a graphite monochromator and a Mo-Ka fine-focus
sealed tube (l = 0.71073 Å). For thin-layer chromatography (TLC),
silica gel plates Merck 60 F254 were used. Melting points were
measured in open capillary tubes and are uncorrected.
sented in Figure 3.15
Ethyl 4-(9-Ethyl-9H-carbazol-3-ylamino)-2-(4-nitrophenyl)-5-
oxo-2,5-dihydro-3-furancarboxylate (4a); Typical Procedure
In a round-bottom flask equipped with a magnetic stirrer bar, and
containing 9-ethyl-9H-carbazol-3-amine (3a; 0.223 g, 1.0 mmol)
and diethyl acetylenedicarboxylate (2a; 0.204 g, 1.2 mmol) in
MeCN (2.7 mL) and H2O (0.3 mL) as solvent, were added p-ni-
trobenzaldehyde (1a; 0.151 g, 1 mmol) and KOH (0.056 g, 1
mmol). The reaction mixture was stirred at r.t. for 30 min. After
completion of the reaction, as indicated by TLC, H2O (10 mL) was
added to the crude reaction mass. Then, the aqueous layer was ex-
tracted with CH2Cl2 (3 × 20 mL). The combined organic layers
were dried (Na2SO4), filtered and concentrated under reduced pres-
sure. Purification by column chromatography on silica gel (EtOAc–
hexane, 1:9) afforded 4a; yield: 0.436 g (90%).
Figure 3 Crystal structure of 6b
Mp 199–201 °C; Rf = 0.31 (EtOAc–hexanes, 1:9).
IR (KBr): 3314, 2978, 1784, 1672, 1234 cm–1.
In summary, we have described a highly efficient, three-
component synthesis of new (carbazolylamino)furanones
and carbazolyltetrahydropyrimidines in good yields. The
important features of this synthetic method are the mild
reaction conditions, the inexpensive starting materials and
the avoidance of the use of expensive catalysts.
1H NMR (400 MHz, CDCl3): d = 8.41 (s, 1 H), 8.25 (d, J = 8.0 Hz,
2 H), 8.05 (d, J = 7.4 Hz, 1 H), 7.91 (s, 1 H), 7.55 (d, J = 8.2 Hz, 2
H), 7.48 (t, J = 8.4 Hz, 1 H), 7.42–7.36 (m, 2 H), 7.31–7.29 (m, 1
H), 7.24–7.21 (m, 1 H), 6.13 (s, 1 H), 4.37 (q, J = 6.0 Hz, 2 H), 4.10
(q, J = 6.9 Hz, 2 H), 1.45 (t, J = 6.9 Hz, 3 H), 1.08 (t, J = 7.1 Hz, 3
H).
EtOOC
H
COOEt
EtOOC
NH
2a
NH2
5 + 3a
COOEt
a
b
EtOOC
EtOOC
N
N
3a
Et
Et
HN
NH
EtOOC
EtOOC
N
N
5
Et
N
Et
N
c
N
6a
N
Et
Et
a = hydroamination, b = Mannich-type reaction, c = dehydration
Scheme 2 Proposed mechanism for the formation of 6a
Synthesis 2011, No. 20, 3307–3317 © Thieme Stuttgart · New York

3312
S. Ramesh, R. Nagarajan
PAPER
13C NMR (100 MHz, CDCl3): d = 166.2, 163.9, 148.3, 143.6, 140.6,
139.3, 138.3, 128.7, 128.4, 126.1, 123.7, 122.9, 122.8, 122.5, 120.6,
119.0, 116.4, 111.3, 108.7, 108.3 (Aromatic C), 79.0, 60.8, 37.7,
14.0, 13.9 (Aliphatic C).
Ethyl 4-(9-Ethyl-9H-carbazol-3-ylamino)-5-oxo-2-phenyl-2,5-
dihydro-3-furancarboxylate (4e)
Yield: 0.319 g (72%); mp 145–147 °C.
IR (KBr): 3314, 2287, 1263, 887 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.40 (s, 1 H), 8.08 (d, J = 7.7 Hz,
1 H), 7.93 (s, 1 H), 7.51–7.47 (m, 1 H), 7.42–7.35 (m, 7 H), 7.34–
7.32 (m, 1 H), 7.24 (t, J = 7.2 Hz, 1 H), 6.09 (s, 1 H), 4.36 (q, J = 6.5
Hz, 2 H), 4.10 (q, J = 7.1 Hz, 2 H), 1.45 (t, J = 7.2 Hz, 3 H), 1.06 (t,
J = 7.8 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 166.8, 164.3, 140.6, 139.2, 138.1,
136.4, 129.3, 129.1, 128.5, 127.5, 126.0, 122.9, 122.7, 120.7, 118.9,
116.1, 112.7, 108.7, 108.3 (Aromatic C), 80.7, 60.5, 37.7, 13.96,
13.90 (Aliphatic C).
MS (positive mode): m/z = 486 [M + H]+.
Anal. Calcd for C27H23N3O6: C, 66.80; H, 4.78; N, 8.66. Found: C,
66.72; H, 4.85; N, 8.58.
Ethyl 4-(9-Ethyl-9H-carbazol-3-ylamino)-2-(4-fluorophenyl)-5-
oxo-2,5-dihydro-3-furancarboxylate (4b)
Yield: 0.398 g (87%); mp 120–122 °C.
IR (KBr): 3315, 2976, 1494, 1232, 1118 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.41 (s, 1 H), 8.07 (d, J = 6.4 Hz,
1 H), 7.93 (s, 1 H), 7.50 (t, J = 7.4 Hz, 1 H), 7.42–7.31 (m, 5 H),
7.24 (t, J = 7.8 Hz, 1 H), 7.09 (t, J = 8.2 Hz, 2 H), 6.07 (s, 1 H), 4.36
(q, J = 7.0 Hz, 2 H), 4.10 (q, J = 8.2 Hz, 2 H), 1.45 (t, J = 6.2 Hz, 3
H), 1.07 (t, J = 6.6 Hz, 3 H).
MS (negative mode): m/z = 439 [M – H]+.
Anal. Calcd for C27H24N2O4: C, 73.62; H, 5.49; N, 6.36. Found: C,
73.48; H, 5.45; N, 6.41.
13C NMR (100 MHz, CDCl3): d = 166.6, 164.4, 164.2, 161.9, 140.6,
139.3, 138.2, 132.2, 129.4, 129.3, 129.1, 126.0, 122.9, 122.7, 122.6,
120.6, 118.9, 116.2, 115.7, 115.4, 112.2, 108.7, 108.3 (Aromatic C),
79.9, 60.0, 37.7, 13.9, 13.8 (Aliphatic C).
Ethyl 4-(9-Ethyl-9H-carbazol-3-ylamino)-2-(4-methylphenyl)-
5-oxo-2,5-dihydro-3-furancarboxylate (4f)
Yield: 0.295 g (65%); mp 118–122 °C.
IR (KBr): 3439, 2924, 1232, 1039, 750 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.35 (s, 1 H), 8.06 (d, J = 7.7 Hz,
1 H), 7.92 (s, 1 H), 7.48 (t, J = 7.4 Hz, 1 H), 7.42–7.40 (m, 1 H),
7.38–7.36 (m, 1 H), 7.33–7.31 (m, 1 H), 7.27–7.25 (m, 2 H), 7.21 (t,
J = 8.0 Hz, 3 H), 6.06 (s, 1 H), 4.37 (q, J = 7.2 Hz, 2 H), 4.09 (q,
J = 6.8 Hz, 2 H), 2.38 (s, 3 H), 1.45 (t, J = 7.2 Hz, 3 H), 1.07 (t,
J = 7.1 Hz, 3 H).
MS (positive mode): m/z = 459 [M + H]+, 460 [M + 2]+.
Anal. Calcd for C27H23FN2O4: C, 70.73; H, 5.06; N, 6.11. Found: C,
70.65; H, 5.11; N, 6.21.
Ethyl 2-(4-Chlorophenyl)-4-(9-ethyl-9H-carbazol-3-ylamino)-
5-oxo-2,5-dihydro-3-furancarboxylate (4c)
Yield: 0.403 g (85%); mp 135–137 °C.
IR (KBr): 3431, 2976, 1780, 1120, 455 cm–1.
13C NMR (100 MHz, CDCl3): d = 166.9, 164.3, 140.6, 139.1, 139.0,
138.1, 133.4, 129.4, 129.2, 127.4, 125.9, 122.9, 122.7, 120.6, 118.9,
116.0, 112.7, 108.6, 108.2 (Aromatic C), 80.6, 60.5, 37.7, 21.3,
13.9, 13.8 (Aliphatic C).
1H NMR (400 MHz, CDCl3): d = 8.39 (s, 1 H), 8.07 (d, J = 7.7 Hz,
1 H), 7.92 (s, 1 H), 7.49 (t, J = 7.4 Hz, 1 H), 7.42–7.36 (m, 4 H),
7.33–7.31 (m, 3 H), 7.26–7.22 (m, 1 H), 6.05 (s, 1 H), 4.37 (q,
J = 7.1 Hz, 2 H), 4.10 (q, J = 7.1 Hz, 2 H), 1.45 (t, J = 7.1 Hz, 3 H),
1.08 (t, J = 7.1 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 166.5, 164.1, 140.6, 139.3, 138.2,
135.0, 129.1, 128.9, 128.8, 126.1, 122.9, 122.7, 120.6, 118.9, 116.2,
112.0, 108.7, 108.3 (Aromatic C), 79.8, 60.0, 37.7, 14.0, 13.9 (Ali-
phatic C).
MS (positive mode): m/z = 456 [M + 2]+.
Anal. Calcd for C28H26N2O4: C, 73.99; H, 5.77; N, 6.16. Found: C,
73.85; H, 5.71; N, 6.22.
Ethyl 4-(9-Ethyl-9H-carbazol-3-ylamino)-2-(4-methoxyphe-
nyl)-5-oxo-2,5-dihydro-3-furancarboxylate (4g)
Yield: 0.282 g (60%); mp 154–156 °C.
MS (positive mode): m/z = 475 [M + H]+, 476 [M + 2]+.
IR (KBr): 3325, 1763, 1230, 1149, 462 cm–1.
Anal. Calcd for C27H23ClN2O4: C, 68.28; H, 4.88; N, 5.90. Found:
C, 68.11; H, 4.91; N, 5.85.
1H NMR (400 MHz, CDCl3): d = 8.43 (s, 1 H), 8.04 (d, J = 7.4 Hz,
1 H), 7.89 (s, 1 H), 7.47–7.45 (m, 1 H), 7.42–7.36 (m, 2 H), 7.32–
7.28 (m, 3 H), 7.21 (t, J = 7.1 Hz, 1 H), 6.91 (d, J = 6.8 Hz, 2 H),
6.05 (s, 1 H), 4.38 (q, J = 6.4 Hz, 2 H), 4.06 (q, J = 6.5 Hz, 2 H),
3.82 (s, 3 H), 1.44 (t, J = 5.6 Hz, 3 H), 1.03 (t, J = 6.8 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 166.8, 163.9, 160.0, 140.3, 138.7,
137.8, 129.5, 128.7, 128.2, 125.9, 122.4, 120.4, 118.7, 115.7, 113.8,
112.5, 108.6, 108.1 (Aromatic C), 80.4, 60.3, 55.2, 37.5, 13.8, 13.7
(Aliphatic C).
Ethyl 2-(4-Bromophenyl)-4-(9-ethyl-9H-carbazol-3-ylamino)-
5-oxo-2,5-dihydro-3-furancarboxylate (4d)
Yield: 0.430 g (83%); mp 143–145 °C.
IR (KBr): 3310, 2930, 1672, 1120, 806 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.41 (s, 1 H), 8.08 (d, J = 7.6 Hz,
1 H), 7.93 (s, 1 H), 7.55–7.48 (m, 3 H), 7.42–7.40 (m, 1 H), 7.34 (q,
J = 8.5 Hz, 2 H), 7.27–7.23 (m, 3 H), 6.03 (s, 1 H), 4.35 (q, J = 6.8
Hz, 2 H), 4.10 (q, J = 6.9 Hz, 2 H), 1.44 (t, J = 7.0 Hz, 3 H), 1.08 (t,
J = 7.0 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 166.6, 164.1, 140.6, 139.2, 138.2,
135.6, 131.7, 129.2, 129.1, 126.1, 123.2, 122.9, 122.7, 122.6, 120.6,
118.9, 116.2, 112.0, 108.7, 108.3 (Aromatic C), 79.9, 60.6, 37.7,
14.0, 13.9 (Aliphatic C).
MS (positive mode): m/z = 471 [M + H]+.
Anal. Calcd for C28H26N2O5: C, 71.47; H, 5.57; N, 5.95. Found: C,
71.32; H, 5.62; N, 5.86.
Ethyl 2-(2,4-Dichlorophenyl)-4-(9-ethyl-9H-carbazol-3-ylami-
no)-5-oxo-2,5-dihydro-3-furancarboxylate (4h)
Yield: 0.422 g (83%); mp 120–122 °C.
MS (positive mode): m/z = 519/521 [M + H]+.
IR (KBr): 3352, 1782, 1155, 1005, 765 cm–1.
Anal. Calcd for C27H23BrN2O4: C, 62.44; H, 4.46; N, 5.39. Found:
C, 62.31; H, 4.52; N, 5.31.
1H NMR (400 MHz, CDCl3): d = 8.47 (s, 1 H), 8.06 (d, J = 7.6 Hz,
1 H), 7.91 (s, 1 H), 7.51–7.47 (m, 2 H), 7.42–7.36 (m, 2 H), 7.32–
7.21 (m, 3 H), 7.19–7.16 (m, 1 H), 6.55 (s, 1 H), 4.37 (q, J = 7.0 Hz,
2 H), 4.11 (q, J = 6.2 Hz, 2 H), 1.45 (t, J = 7.0 Hz, 3 H), 1.08 (t,
J = 6.6 Hz, 3 H).
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Multicomponent Synthesis of Heteroaryl-Substituted Carbazoles
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13C NMR (100 MHz, CDCl3): d = 166.3, 164.1, 140.6, 140.0, 138.2,
135.5, 135.4, 132.5, 129.8, 129.5, 128.5, 127.5, 126.1, 122.9, 122.7,
122.6, 120.6, 118.9, 116.2, 110.9, 108.7, 108.3 (Aromatic C), 76.2,
60.7, 37.7, 13.96, 13.90 (Aliphatic C).
Ethyl 2-(1,3-Benzodioxol-5-yl)-4-(9-ethyl-9H-carbazol-3-ylami-
no)-5-oxo-2,5-dihydro-3-furancarboxylate (4l)
Yield: 0.378 g (78%); mp 163–165 °C.
IR (KBr): 3310, 2930, 1491, 1035, 636 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.37 (s, 1 H), 8.08 (d, J = 7.6 Hz,
1 H), 7.92 (s, 1 H), 7.50 (t, J = 7.4 Hz, 1 H), 7.43–7.37 (m, 2 H),
7.34–7.32 (m, 1 H), 7.24 (t, J = 7.3 Hz, 1 H), 6.92 (d, J = 7.6 Hz, 1
H), 6.83 (d, J = 9.2 Hz, 2 H), 6.01 (s, 3 H), 4.39 (q, J = 7.0 Hz, 2 H),
4.13 (q, J = 7.0 Hz, 2 H), 1.47 (t, J = 5.7 Hz, 3 H), 1.10 (t, J = 6.9
Hz, 3 H).
MS (positive mode): m/z = 509 [M + H]+.
Anal. Calcd for C27H22Cl2N2O4: C, 63.66; H, 4.35; N, 5.50. Found:
C, 63.45; H, 4.31; N, 5.56.
Ethyl 2-(2-Bromophenyl)-4-(9-ethyl-9H-carbazol-3-ylamino)-
5-oxo-2,5-dihydro-3-furancarboxylate (4i)
Yield: 0.441 g (85%); mp 130–135 °C.
IR (KBr): 3356, 2968, 1684, 1249, 671 cm–1.
13C NMR (100 MHz, CDCl3): d = 166.7, 164.3, 148.3, 147.9, 140.6,
139.2, 138.1, 130.2, 129.3, 126.0, 122.9, 122.7, 121.9, 120.7, 118.9,
116.1, 112.3, 108.7, 108.3, 107.4 (Aromatic C), 101.4, 80.6, 60.6,
37.7, 14.1, 13.9 (Aliphatic C).
1H NMR (400 MHz, CDCl3): d = 8.50 (s, 1 H), 8.08 (d, J = 7.9 Hz,
1 H), 7.94 (s, 1 H), 7.64 (d, J = 8.3 Hz, 1 H), 7.50 (t, J = 7.7 Hz, 1
H), 7.42–7.40 (m, 1 H), 7.38–7.32 (m, 3 H), 7.26–7.22 (m, 3 H),
6.64 (s, 1 H), 4.35 (q, J = 7.2 Hz, 2 H), 4.10 (q, J = 6.8 Hz, 2 H),
1.44 (t, J = 7.1 Hz, 3 H), 1.06 (t, J = 7.1 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 166.6, 164.2, 140.6, 140.0, 138.2,
135.3, 133.3, 130.6, 129.1, 128.7, 127.7, 126.0, 124.9, 122.9, 122.7,
122.6, 120.6, 118.9, 116.2, 111.7, 108.7, 108.3 (Aromatic C), 79.2,
60.6, 37.7, 13.98, 13.91 (Aliphatic C).
MS (negative mode): m/z = 483 [M – H]+.
Anal. Calcd for C28H24N2O6: C, 69.41; H, 4.99; N, 5.78. Found: C,
69.52; H, 4.91; N, 5.65.
Ethyl 2-(2-Chloro-3-quinolyl)-4-(9-ethyl-9H-carbazol-3-ylami-
no)-5-oxo-2,5-dihydro-3-furancarboxylate (4m)
Yield: 0.446 g (85%); mp 139–141 °C.
MS (positive mode): m/z = 519 [M + H]+, 520 [M + 2]+.
IR (KBr): 3306, 2924, 1776, 1234, 750 cm–1.
Anal. Calcd for C27H23BrN2O4: C, 62.44; H, 4.46; N, 5.39. Found:
C, 62.34; H, 4.39; N, 5.45.
1H NMR (400 MHz, CDCl3): d = 8.59 (s, 1 H), 8.07–8.05 (m, 3 H),
7.96 (s, 1 H), 7.83 (d, J = 8.0 Hz, 1 H), 7.78 (t, J = 7.7 Hz, 1 H), 7.58
(t, J = 7.5 Hz, 1 H), 7.49 (t, J = 7.6 Hz, 1 H), 7.42–7.37 (m, 3 H),
7.24 (t, J = 7.8 Hz, 1 H), 6.67 (s, 1 H), 4.35 (q, J = 6.8 Hz, 2 H),
4.13–4.03 (m, 2 H), 1.44 (t, J = 7.0 Hz, 3 H), 1.03 (t, J = 7.0 Hz, 3
H).
Ethyl 4-(9-Ethyl-9H-carbazol-3-ylamino)-2-(1-naphthyl)-5-
oxo-2,5-dihydro-3-furancarboxylate (4j)
Yield: 0.368 g (75%); mp 134–136 °C.
IR (KBr): 3468, 2926, 1460, 1116, 748 cm–1.
13C NMR (100 MHz, CDCl3): d = 166.2, 164.1, 150.1, 147.6, 140.6,
140.4, 138.3, 138.1, 131.4, 128.8, 128.4, 127.8, 127.6, 126.8, 126.1,
122.9, 122.8, 122.6, 120.6, 118.9, 116.3, 110.3, 108.7, 108.3 (Aro-
matic C), 77.0, 60.8, 37.7, 14.0, 13.9 (Aliphatic C).
1H NMR (400 MHz, CDCl3): d = 8.58 (s, 1 H), 8.32 (d, J = 8.5 Hz,
1 H), 8.06 (d, J = 8.1 Hz, 1 H), 7.95–7.89 (m, 3 H), 7.63 (t, J = 7.2
Hz, 1 H), 7.55 (t, J = 7.5 Hz, 1 H), 7.48 (t, J = 7.4 Hz, 2 H), 7.42–
7.37 (m, 4 H), 7.23–7.21 (m, 1 H), 6.97 (s, 1 H), 4.37 (q, J = 7.2 Hz,
2 H), 4.07 (q, J = 7.0 Hz, 2 H), 1.45 (t, J = 7.0 Hz, 3 H), 0.92 (t,
J = 6.8 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 166.5, 164.7, 140.6, 140.2, 138.2,
133.9, 132.3, 132.1, 129.9, 129.3, 128.8, 128.1, 126.7, 125.9, 125.1,
123.4, 122.9, 122.7, 120.6, 118.9, 116.1, 111.6, 108.6, 108.3 (Aro-
matic C), 76.7, 60.5, 37.7, 13.96, 13.90 (Aliphatic C).
MS (positive mode): m/z = 527 [M + 2]+.
Anal. Calcd for C30H24ClN3O4: C, 68.50; H, 4.60; N, 7.99. Found:
C, 68.45; H, 4.66; N, 8.12.
Ethyl 2-(9-Ethyl-9H-carbazol-3-yl)-4-(9-ethyl-9H-carbazol-3-
ylamino)-5-oxo-2,5-dihydro-3-furancarboxylate (4n)
Yield: 0.445 g (80%); mp 158–160 °C.
MS (negative mode): m/z = 489 [M – H]+.
IR (KBr): 3369, 2924, 1693, 1012, 746 cm–1.
Anal. Calcd for C31H26N2O4: C, 75.90; H, 5.34; N, 5.71. Found: C,
75.81; H, 5.29; N, 5.62.
1H NMR (400 MHz, CDCl3): d = 8.40 (s, 1 H), 8.12–8.05 (m, 3 H),
7.94 (s, 1 H), 7.47–7.35 (m, 8 H), 7.26–7.19 (m, 2 H), 6.29 (s, 1 H),
4.33–4.32 (m, 4 H), 4.05–4.00 (m, 2 H), 1.42–1.40 (m, 6 H), 0.98 (t,
J = 6.7 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 167.1, 164.5, 140.6, 140.4, 139.2,
138.1, 129.6, 126.5, 125.9, 124.9, 123.0, 122.9, 122.8, 122.7, 122.6,
120.7, 120.6, 120.1, 119.2, 118.9, 115.9, 113.2, 108.7, 108.5, 108.3
(Aromatic C), 81.7, 60.5, 37.7, 14.0, 13.9, 13.8 (Aliphatic C).
Ethyl 4-(9-Ethyl-9H-carbazol-3-ylamino)-2-(2-naphthyl)-5-
oxo-2,5-dihydro-3-furancarboxylate (4k)
Yield: 0.353 g (72%); mp 148–152 °C.
IR (KBr): 3342, 2974, 1766, 1230, 748 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.49 (s, 1 H), 8.11 (d, J = 7.1 Hz,
1 H), 7.99 (s, 1 H), 7.92–7.88 (m, 4 H), 7.56–7.50 (m, 3 H), 7.47–
7.41 (m, 2 H), 7.38 (s, 2 H), 7.27 (t, J = 7.2 Hz, 1 H), 6.28 (s, 1 H),
4.35 (q, J = 7.0 Hz, 2 H), 4.07 (q, J = 7.9 Hz, 2 H), 1.45 (t, J = 7.0
Hz, 3 H), 1.03 (t, J = 7.0 Hz, 3 H).
MS (positive mode): m/z = 559 [M + 2]+.
Anal. Calcd for C35H31N3O4: C, 75.38; H, 5.60; N, 7.54. Found: C,
75.42; H, 5.66; N, 7.45.
13C NMR (100 MHz, CDCl3): d = 166.9, 164.4, 140.6, 139.3, 138.2,
133.7, 133.1, 129.3, 128.5, 128.2, 127.8, 127.6, 126.7, 126.5, 126.0,
124.2, 122.9, 122.7, 120.7, 118.9, 116.1, 112.7, 108.7, 108.3 (Aro-
matic C), 80.9, 60.6, 37.7, 13.99, 13.92 (Aliphatic C).
Ethyl 2-(5-Chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)-4-(9-
ethyl-9H-carbazol-3-ylamino)-5-oxo-2,5-dihydro-3-furancar-
boxylate (4o)
Yield: 0.388 g (70%); mp 175–177 °C.
MS (positive mode): m/z = 492 [M + H]+.
IR (KBr): 3431, 1668, 1275, 663 cm–1.
Anal. Calcd for C31H26N2O4: C, 75.90; H, 5.34; N, 5.71. Found: C,
75.81; H, 5.40; N, 5.76.
1H NMR (400 MHz, CDCl3): d = 8.45 (s, 1 H), 8.07 (d, J = 7.7 Hz,
1 H), 7.92 (s, 1 H), 7.62–7.48 (m, 5 H), 7.46–7.38 (m, 3 H), 7.33–
7.31 (m, 1 H), 7.28–7.22 (m, 1 H), 6.21 (s, 1 H), 4.39 (q, J = 7.8 Hz,
Synthesis 2011, No. 20, 3307–3317 © Thieme Stuttgart · New York

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S. Ramesh, R. Nagarajan
PAPER
2 H), 4.20 (q, J = 6.8 Hz, 2 H), 2.36 (s, 3 H), 1.46 (t, J = 7.1 Hz, 3
H), 1.18 (t, J = 7.8 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 166.5, 164.2, 148.7, 140.6, 139.8,
138.2, 137.9, 129.2, 129.1, 128.4, 127.0, 126.0, 125.1, 122.9, 122.7,
122.6, 120.6, 118.9, 116.1, 112.0, 110.1, 108.6, 108.3 (Aromatic C),
72.5, 60.6, 37.7, 14.1, 13.9, 12.9 (Aliphatic C).
Ethyl 4-(6-Chloro-9-ethyl-9H-carbazol-3-ylamino)-2-(4-nitro-
phenyl)-5-oxo-2,5-dihydro-3-furancarboxylate (4s)
Yield: 0.467 g (90%); mp 119–121 °C.
IR (KBr): 3323, 2980, 1641, 1201, 736 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.43 (s, 1 H), 8.25 (d, J = 7.9 Hz,
2 H), 7.99 (s, 1 H), 7.85 (s, 1 H), 7.55 (d, J = 7.9 Hz, 2 H), 7.42 (d,
J = 8.7 Hz, 1 H), 7.38–7.30 (m, 3 H), 6.14 (s, 1 H), 4.33 (q, J = 6.8
Hz, 2 H), 4.12 (q, J = 6.8 Hz, 2 H), 1.43 (t, J = 6.9 Hz, 3 H), 1.10 (t,
J = 6.9 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 166.1, 163.8, 148.3, 143.5, 139.3,
138.9, 138.7, 129.0, 128.4, 126.2, 124.5, 123.7, 123.6, 123.5, 122.0,
120.3, 116.5, 111.7, 109.7, 108.7 (Aromatic C), 79.0, 60.9, 37.9,
14.0, 13.8 (Aliphatic C).
MS (positive mode): m/z = 556 [M + 2]+.
Anal. Calcd for C31H27ClN4O4: C, 67.08; H, 4.90; N, 10.09. Found:
C, 67.18; H, 4.85; N, 10.21.
Methyl 4-(9-Ethyl-9H-carbazol-3-ylamino)-2-(4-nitrophenyl)-
5-oxo-2,5-dihydro-3-furancarboxylate (4p)
Yield: 0.433 g (92%); mp 186–188 °C.
IR (KBr): 3300, 2916, 2843, 1770, 1454, 829 cm–1.
MS (positive mode): m/z = 520 [M + H]+, 521 [M + 2]+.
1H NMR (400 MHz, CDCl3): d = 8.44 (s, 1 H), 8.24 (d, J = 8.7 Hz,
2 H), 8.08 (d, J = 7.7 Hz, 1 H), 7.94 (d, J = 1.6 Hz, 1 H), 7.55 (d,
J = 8.7 Hz, 2 H), 7.51 (d, J = 7.3 Hz, 1 H), 7.44–7.38 (m, 2 H),
7.34–7.32 (m, 1 H), 7.26 (t, J = 7.4 Hz, 1 H), 6.12 (s, 1 H), 4.37 (q,
J = 7.2 Hz, 2 H), 3.64 (s, 3 H), 1.46 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 166.1, 164.2, 148.3, 143.5, 140.6,
139.4, 138.3, 128.7, 128.4, 126.2, 123.8, 122.9, 122.8, 122.5, 120.6,
119.0, 116.5, 110.9, 108.8, 108.3 (Aromatic C), 78.9, 51.7, 37.7,
13.9 (Aliphatic C).
Anal. Calcd for C27H22ClN3O6: C, 62.37; H, 4.26; N, 8.08. Found:
C, 62.28; H, 4.31; N, 8.15.
Ethyl 4-(6-Bromo-9-ethyl-9H-carbazol-3-ylamino)-2-(4-nitro-
phenyl)-5-oxo-2,5-dihydro-3-furancarboxylate (4t)
Yield: 0.507 g (90%); mp 145–147 °C.
IR (KBr): 3314, 1682, 1232, 804 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.43 (s, 1 H), 8.25 (d, J = 8.2 Hz,
2 H), 8.14 (s, 1 H), 7.84 (s, 1 H), 7.55 (d, J = 8.1 Hz, 3 H), 7.34 (q,
J = 8.5 Hz, 2 H), 7.27 (d, J = 8.4 Hz, 1 H), 6.13 (s, 1 H), 4.32 (q,
J = 7.1 Hz, 2 H), 4.12 (q, J = 6.9 Hz, 2 H), 1.43 (t, J = 6.8 Hz, 3 H),
1.10 (t, J = 6.9 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 166.1, 163.9, 148.3, 143.5, 139.3,
139.2, 138.6, 129.1, 128.8, 128.4, 124.2, 123.8, 123.5, 123.3, 121.9,
116.5, 111.8, 111.7, 110.2, 108.6 (Aromatic C), 79.0, 60.9, 37.9,
14.0, 13.8 (Aliphatic C).
MS (positive mode): m/z = 472 [M + H]+.
Anal. Calcd for C26H21N3O6: C, 66.24; H, 4.49; N, 8.91. Found: C,
66.35; H, 4.41; N, 8.79.
Ethyl 4-(9-Methyl-9H-carbazol-3-ylamino)-2-(4-nitrophenyl)-
5-oxo-2,5-dihydro-3-furancarboxylate (4q)
Yield: 0.423 g (90%); mp 170–172 °C.
IR (KBr): 3308, 2978, 1647, 1116, 746 cm–1.
MS (negative mode): m/z = 563 [M]+, 565 [M + 2]+.
1H NMR (400 MHz, CDCl3): d = 8.43 (s, 1 H), 8.25 (d, J = 7.9 Hz,
2 H), 8.05 (d, J = 7.5 Hz, 1 H), 7.91 (s, 1 H), 7.57–7.48 (m, 3 H),
7.42–7.31 (m, 3 H), 7.26–7.22 (m, 1 H), 6.13 (s, 1 H), 4.12 (q,
J = 7.0 Hz, 2 H), 3.86 (s, 3 H), 1.10 (t, J = 6.1 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 166.0, 163.9, 143.6, 141.6, 139.4,
128.7, 128.4, 126.2, 123.7, 122.9, 122.4, 120.5, 119.1, 116.3, 111.3,
108.7, 108.3 (Aromatic C), 79.0, 60.8, 29.3, 14.1 (Aliphatic C).
Anal. Calcd for C27H22BrN3O6: C, 57.46; H, 3.93; N, 7.45. Found:
C, 57.39; H, 3.85; N, 7.38.
Diethyl 1,3-Bis(9-ethyl-9H-carbazol-3-yl)-1,2,3,6-tetrahydro-
4,5-pyrimidinedicarboxylate (6a); Typical Procedure
In a round-bottom flask equipped with a magnetic stirrer bar, and
containing 9-ethyl-9H-carbazol-3-amine (3a; 0.446 g, 2.0 mmol)
and diethyl acetylenedicarboxylate (2a; 0.204 g, 1.2 mmol) in
[Bmim][BF4] (3 mL) as solvent, was added 37% formaldehyde soln
(5; 0.2 mL, 6 mmol). The reaction mixture was stirred at 110 °C for
1 h. After completion of the reaction, as indicated by TLC, H2O (10
mL) was added to the crude reaction mass. Then, the aqueous layer
was extracted with CH2Cl2 (3 × 20 mL). The combined organic lay-
ers were dried (Na2SO4), filtered and concentrated under reduced
pressure. Purification by column chromatography on silica gel (hex-
ane–EtOAc, 7:3) afforded 6a; yield: 0.515 g (84%).
MS (positive mode): m/z = 472 [M + H]+.
Anal. Calcd for C26H21N3O6: C, 66.24; H, 4.49; N, 8.91. Found: C,
66.31; H, 4.52; N, 8.83.
Ethyl 4-(9-Benzyl-9H-carbazol-3-ylamino)-2-(4-nitrophenyl)-5-
oxo-2,5-dihydro-3-furancarboxylate (4r)
Yield: 0.497 g (91%); mp 159–161 °C.
IR (KBr): 3294, 2976, 1514, 850 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.41 (s, 1 H), 8.24 (d, J = 8.5 Hz,
2 H), 8.09 (d, J = 7.6 Hz, 1 H), 7.95 (s, 1 H), 7.55 (d, J = 8.4 Hz, 2
H), 7.46 (t, J = 7.6 Hz, 1 H), 7.38 (d, J = 8.1 Hz, 1 H), 7.33–7.26 (m,
6 H), 7.16–7.15 (m, 2 H), 6.13 (s, 1 H), 5.50 (s, 2 H), 4.09 (q, J = 6.9
Hz, 2 H), 1.07 (t, J = 6.9 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 166.3, 163.8, 148.3, 143.6, 141.3,
139.1, 138.9, 136.9, 129.2, 128.9, 128.4, 127.6, 126.4, 123.8, 123.1,
122.9, 122.7, 120.6, 119.5, 116.3, 111.5, 109.2, 108.9 (Aromatic C),
79.1, 60.9, 46.7, 14.0 (Aliphatic C).
Mp 120–122 °C; Rf = 0.31 (EtOAc–hexanes, 3:7).
IR (KBr): 3051, 1738, 1693, 1230, 746 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.96 (d, J = 7.7 Hz, 1 H), 7.81–
7.80 (m, 2 H), 7.76 (s, 1 H), 7.48–7.42 (m, 2 H), 7.39–7.37 (m, 2 H),
7.29–7.25 (m, 3 H), 7.19–7.11 (m, 3 H), 5.04 (s, 2 H), 4.41 (s, 2 H),
4.34–4.29 (m, 4 H), 4.26–4.21 (m, 2 H), 3.95 (q, J = 7.1 Hz, 2 H),
1.42–1.36 (m, 6 H), 1.30 (t, J = 7.1 Hz, 3 H), 0.90 (t, J = 7.2 Hz, 3
H).
13C NMR (100 MHz, CDCl3): d = 166.1, 164.4, 148.1, 141.9, 140.5,
138.5, 136.0, 135.1, 126.1, 125.6, 124.5, 123.2, 122.9, 122.8, 122.5,
120.5, 120.4, 119.6, 119.1, 118.8, 118.5, 110.9, 109.1, 108.7, 108.5
(Aromatic C), 97.7, 71.7, 61.4, 60.0, 49.1, 37.7, 37.6, 14.5, 13.9,
13.7 (Aliphatic C).
MS (positive mode): m/z = 548 [M + H]+.
Anal. Calcd for C32H25N3O6: C, 70.19; H, 4.60; N, 7.67. Found: C,
70.09; H, 4.55; N, 7.72.
MS (positive mode): m/z = 614 [M]+, 615 [M + 1]+.
Synthesis 2011, No. 20, 3307–3317 © Thieme Stuttgart · New York

PAPER
Multicomponent Synthesis of Heteroaryl-Substituted Carbazoles
3315
Anal. Calcd for C38H38N4O4: C, 74.24; H, 6.23; N, 9.11. Found: C,
74.32; H, 6.18; N, 9.15.
1H NMR (400 MHz, CDCl3): d = 7.97 (d, J = 7.7 Hz, 1 H), 7.83–
7.81 (m, 2 H), 7.71 (d, J = 1.4 Hz, 1 H), 7.48–7.46 (m, 2 H), 7.37
(d, J = 8.1 Hz, 2 H), 7.29–7.23 (m, 3 H), 7.18–7.13 (m, 3 H), 5.06
(s, 2 H), 4.44 (s, 2 H), 3.80 (s, 6 H), 3.79 (s, 3 H), 3.50 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 166.5, 164.9, 148.2, 141.9, 141.6,
141.5, 139.5, 137.2, 135.1, 126.2, 125.7, 124.3, 123.1, 122.9, 122.6,
122.3, 120.4, 120.3, 119.5, 119.2, 118.5, 118.4, 110.8, 109.1,
108.72, 108.66, 108.5 (Aromatic C), 97.4, 71.8, 52.4, 51.4, 48.9,
29.2, 29.1 (Aliphatic C).
Dimethyl 1,3-Bis(9-ethyl-9H-carbazol-3-yl)-1,2,3,6-tetrahydro-
4,5-pyrimidinedicarboxylate (6b)
Yield: 0.515 g (88%); mp 134–136 °C.
IR (KBr): 3059, 1269, 1111, 746 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.00 (d, J = 7.7 Hz, 1 H), 7.88–
7.84 (m, 2 H), 7.76 (d, J = 1.4 Hz, 1 H), 7.48 (q, J = 7.5 Hz, 2 H),
7.42–7.40 (m, 2 H), 7.34–7.32 (m, 2 H), 7.29–7.27 (m, 1 H), 7.22–
7.15 (m, 3 H), 5.09 (s, 2 H), 4.45 (s, 2 H), 4.34 (q, J = 6.8 Hz, 4 H),
3.82 (s, 3 H), 3.55 (s, 3 H), 1.45–1.39 (m, 6 H).
13C NMR (100 MHz, CDCl3): d = 166.6, 164.9, 148.2, 141.8, 140.5,
140.4, 138.5, 136.1, 134.9, 126.2, 125.6, 124.3, 123.3, 123.1, 122.8,
122.5, 120.6, 120.5, 119.5, 119.1, 118.5, 110.8, 109.1, 108.7, 108.5
(Aromatic C), 97.3, 71.7, 52.4, 51.4, 48.9, 37.7, 37.6, 13.9 (Aliphat-
ic C).
MS (positive mode): m/z = 559 [M + H]+.
Anal. Calcd for C34H30N4O4: C, 73.10; H, 5.41; N, 10.03. Found: C,
73.25; H, 5.36; N, 9.89.
Diethyl 1,3-Bis(9-benzyl-9H-carbazol-3-yl)-1,2,3,6-tetrahydro-
4,5-pyrimidinedicarboxylate (6f)
Yield: 0.590 g (80%); mp 166–168 °C.
IR (KBr): 3055, 2926, 1491, 1327, 746 cm–1.
MS (positive mode): m/z = 587 [M + H]+.
1H NMR (400 MHz, CDCl3): d = 8.00 (d, J = 7.4 Hz, 1 H), 7.87–
7.82 (m, 3 H), 7.43–7.32 (m, 4 H), 7.24–7.10 (m, 16 H), 5.46 (d,
J = 7.4 Hz, 4 H), 5.04 (s, 2 H), 4.40 (s, 2 H), 4.24 (q, J = 6.9 Hz, 2
H), 3.97 (q, J = 6.8 Hz, 2 H), 1.31 (t, J = 6.6 Hz, 3 H), 0.86 (t,
J = 6.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 166.0, 164.3, 147.9, 142.3, 141.3,
141.2, 139.2, 137.3, 136.8, 136.7, 135.4, 128.8, 128.7, 127.6, 127.4,
126.38, 126.35, 125.8, 124.7, 123.4, 123.1, 122.9, 122.6, 120.6,
120.4, 119.7, 119.6, 118.9, 118.8, 110.8, 109.6, 109.2, 108.9 (Aro-
matic C), 97.8, 71.4, 61.4, 60.0, 49.2, 46.7, 46.6, 14.5, 13.6 (Ali-
phatic C).
Anal. Calcd for C36H34N4O4: C, 73.70; H, 5.84; N, 9.55. Found: C,
73.65; H, 5.91; N, 9.48.
Ethyl 1,3-Bis(9-ethyl-9H-carbazol-3-yl)-1,2,3,6-tetrahydro-4-
pyrimidinecarboxylate (6c)
Yield: 0.406 g (75%); mp 141–143 °C.
IR (KBr): 3057, 1672, 1379, 1022, 723 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.08 (d, J = 7.8 Hz, 1 H), 8.02 (d,
J = 2.4 Hz, 1 H), 7.90 (d, J = 6.0 Hz, 1 H), 7.80–7.79 (m, 2 H), 7.52
(t, J = 7.2 Hz, 1 H), 7.43 (t, J = 8.4 Hz, 2 H), 7.37–7.30 (m, 4 H),
7.26 (t, J = 8.2 Hz, 1 H), 7.21–7.19 (m, 1 H), 7.15–7.11 (m, 1 H),
5.21 (s, 2 H), 4.44 (s, 2 H), 4.35–4.33 (m, 2 H), 4.32–4.30 (m, 4 H),
1.46 (t, J = 7.2 Hz, 3 H), 1.41–1.34 (m, 6 H).
13C NMR (100 MHz, CDCl3): d = 167.4, 142.4, 142.3, 140.6, 140.4,
137.5, 137.2, 135.9, 126.3, 125.6, 123.6, 123.2, 122.7, 122.5, 120.7,
120.3, 119.3, 118.9, 118.7, 118.4, 111.8, 110.6, 109.2, 109.0, 108.8,
108.5 (Aromatic C), 98.0, 68.2, 59.4, 49.1, 37.7, 37.6, 14.7, 13.9
(Aliphatic C).
MS (negative mode): m/z = 737 [M – H]+.
Anal. Calcd for C48H42N4O4: C, 78.03; H, 5.73; N, 7.58. Found: C,
78.12; H, 5.65; N, 7.51.
Diethyl 1,3-Bis(6-chloro-9-ethyl-9H-carbazol-3-yl)-1,2,3,6-tet-
rahydro-4,5-pyrimidinedicarboxylate (6g)
Yield: 0.567 g (83%); mp 135–140 °C.
IR (KBr): 3439, 2976, 1697, 1226, 655 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.87 (s, 1 H), 7.73 (s, 1 H), 7.68
(s, 1 H), 7.56 (s, 1 H), 7.40–7.37 (m, 2 H), 7.32–7.22 (m, 6 H), 5.04
(s, 2 H), 4.43 (s, 2 H), 4.28 (q, J = 6.4 Hz, 6 H), 4.00 (q, J = 7.0 Hz,
2 H), 1.41–1.32 (m, 9 H), 0.94 (t, J = 7.1 Hz, 3 H).
MS (positive mode): m/z = 543 [M + H]+.
Anal. Calcd for C35H34N4O2: C, 77.46; H, 6.32; N, 10.32. Found: C,
77.32; H, 6.41; N, 10.21.
Diethyl 1,3-Bis(9-methyl-9H-carbazol-3-yl)-1,2,3,6-tetrahydro-
4,5-pyrimidinedicarboxylate (6d)
Yield: 0.498 g (85%); mp 110–112 °C.
IR (KBr): 3057, 2930, 1469, 1103, 632 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.99 (d, J = 6.8 Hz, 1 H), 7.85–
7.82 (m, 2 H), 7.75 (s, 1 H), 7.47 (d, J = 6.7 Hz, 2 H), 7.36 (d,
J = 7.5 Hz, 2 H), 7.29–7.19 (m, 6 H), 5.05 (s, 2 H), 4.45 (s, 2 H),
4.28 (q, J = 6.1 Hz, 2 H), 3.97 (q, J = 6.1 Hz, 2 H), 3.83–3.72 (m, 6
H), 1.34 (t, J = 7.1 Hz, 3 H), 0.94 (t, J = 7.1 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 165.9, 164.3, 147.8, 142.1, 138.8,
138.7, 136.4, 130.5, 126.2, 125.6, 125.1, 124.6, 123.9, 123.8, 123.5,
122.3, 122.0, 120.3, 120.0, 119.9, 118.8, 110.8, 109.7, 109.6, 109.4,
108.9 (Aromatic C), 98.5, 71.7, 61.5, 60.1, 49.1, 37.9, 37.8, 14.4,
13.8, 13.6 (Aliphatic C).
MS (positive mode): m/z = 682 [M+], 684 [M + 2]+.
Anal. Calcd for C38H36Cl2N4O4: C, 66.76; H, 5.31; N, 8.20. Found:
C, 66.58; H, 5.36; N, 8.31.
13C NMR (100 MHz, CDCl3): d = 166.1, 164.4, 148.1, 141.9, 141.5,
139.5, 137.1, 135.2, 126.2, 125.7, 124.5, 123.1, 122.8, 122.6, 122.3,
120.4, 119.6, 119.2, 118.7, 118.5, 110.8, 109.1, 108.7, 108.5 (Aro-
matic C), 97.8, 71.8, 61.4, 60.0, 49.1, 29.2, 14.5, 13.7 (Aliphatic C).
Dimethyl 1,3-Bis(6-chloro-9-ethyl-9H-carbazol-3-yl)-1,2,3,6-
tetrahydro-4,5-pyrimidinedicarboxylate (6h)
Yield: 0.557 g (85%); mp 195–197 °C.
IR (KBr): 3063, 2943, 1294, 746 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.85 (s, 1 H), 7.68 (s, 2 H), 7.52
(s, 1 H), 7.38–7.35 (m, 2 H), 7.28–7.24 (m, 5 H), 7.21–7.18 (m, 1
H), 5.03 (s, 2 H), 4.41 (s, 2 H), 4.29–4.26 (m, 4 H), 3.80 (s, 3 H),
3.54 (s, 3 H), 1.40–1.34 (m, 6 H).
MS (positive mode): m/z = 587 [M + H]+.
Anal. Calcd for C36H34N4O4: C, 73.70; H, 5.84; N, 9.55. Found: C,
73.85; H, 5.81; N, 9.48.
Dimethyl 1,3-Bis(9-methyl-9H-carbazol-3-yl)-1,2,3,6-tetrahy-
dro-4,5-pyrimidinedicarboxylate (6e)
Yield: 0.458 g (82%); mp 184–186 °C.
IR (KBr): 2926, 1745, 1467, 746 cm–1.
13C NMR (100 MHz, CDCl3): d = 166.4, 164.9, 147.9, 142.0,
138.83, 138.80, 138.7, 136.4, 135.4, 126.3, 125.7, 124.9, 124.6,
123.9, 123.7, 123.5, 122.3, 122.2, 120.2, 120.1, 119.9, 118.5, 110.7,
Synthesis 2011, No. 20, 3307–3317 © Thieme Stuttgart · New York

3316
S. Ramesh, R. Nagarajan
PAPER
109.7, 109.6, 109.4, 109.0 (Aromatic C), 98.1, 71.7, 62.5, 61.5,
48.9, 37.9, 37.8, 13.82, 13.79 (Aliphatic C).
MS (positive mode): m/z = 654 [M]+, 656 [M + 2]+.
Kongkathip, B.; Kongkathip, N.; Polysuk, C.; Sridharan, V.
Angew. Chem. Int. Ed. 2005, 44, 7570. (f) Tietze, L. F.;
Sommer, K. M.; Zinngrebe, J.; Stecker, F. Angew. Chem. Int.
Ed. 2005, 44, 257. (g) Pache, S.; Lautens, M. Org. Lett.
2003, 5, 4827.
Anal. Calcd for C36H32Cl2N4O4: C, 65.96; H, 4.92; N, 8.55. Found:
C, 65.88; H, 4.96; N, 8.65.
(2) (a) Faulmann, C.; Cassoux, P. Prog. Inorg. Chem. 2004, 52,
399. (b) Musonda, C. C.; Taylor, D.; Lehman, J.; Gut, J.;
Rosenthal, P. J.; Chibale, K. Bioorg. Med. Chem. Lett. 2004,
14, 3901. (c) De Laszlo, S. E.; Williard, P. G. J. Am. Chem.
Soc. 1985, 107, 199. (d) Fan, L.; Lobkovsky, E.; Ganem, B.
Org. Lett. 2007, 9, 2015.
Diethyl 1,3-Bis(6-bromo-9-ethyl-9H-carbazol-3-yl)-1,2,3,6-tet-
rahydro-4,5-pyrimidinedicarboxylate (6i)
Yield: 0.656 g (85%); mp 95–97 °C.
IR (KBr): 2970, 1736, 1481, 1226 cm–1.
(3) (a) Iskander, G.; Zhang, R.; Chan, D. S.-H.; StC Black, D.;
Alamgir, M.; Kumar, N. Tetrahedron Lett. 2009, 50, 4613.
(b) Boukouvalas, J.; Lachance, N.; Ouellet, M.; Trudeau, M.
Tetrahedron Lett. 1998, 39, 7665. (c) Young, S. S.; Yun-
Jeong, L.; Bum, T. K.; Jung-Nyoung, H. Tetrahedron Lett.
2006, 47, 7427. (d) Vishal, A. M.; Popat, D. S.; Hanumant,
B. B.; Radhika, D. W. Tetrahedron Lett. 2005, 46, 1009.
(e) Murthy, N. S.; Madhav, B.; Vijay, K. A.; Rama, R. K.;
Nageswar, Y. V. D. Tetrahedron 2009, 65, 5251. (f) Sorg,
A.; Siegel, K.; Brückner, R. Chem. Eur. J. 2005, 11, 1610.
(g) Boukouvalas, J.; Pouliot, M. Synlett 2005, 343.
(h) Boukouvalas, J.; Wang, J.-X.; Marion, O.; Ndzi, B. J.
Org. Chem. 2006, 71, 6670. (i) Boukouvalas, J.; Loach, R.
P. J. Org. Chem. 2008, 73, 8109. (j) Patel, R. M.; Argade,
N. P. Synthesis 2010, 1188.
(4) (a) Carter, N. B.; Nadany, A. E.; Sweeney, J. B. J. Chem.
Soc., Perkin Trans. 1 2002, 2324. (b) Chen, Q. H.; Praveen,
P. N.; Knaus, E. E. Bioorg. Med. Chem. 2006, 14, 7898.
(c) Boukouvalas, J.; Cote, S.; Ndzi, B. Tetrahedron Lett.
2007, 48, 105. (d) Zarghi, A.; Praveen, P. N.; Knaus, E. E.
Bioorg. Med. Chem. 2007, 15, 1056. (e) Boukouvalas, J.;
Wang, J.-X.; Marion, O. Tetrahedron Lett. 2007, 48, 7747.
(f) Braun, M.; Hohmann, A.; Rahematpura, J.; Bühne, C.;
Grimme, S. Chem. Eur. J. 2004, 10, 4584.
1H NMR (400 MHz, CDCl3): d = 7.99 (s, 1 H), 7.83 (s, 1 H), 7.69
(s, 1 H), 7.55 (s, 1 H), 7.49 (t, J = 7.8 Hz, 2 H), 7.28–7.21 (m, 6 H),
5.02 (s, 2 H), 4.41 (s, 2 H), 4.26 (q, J = 7.1 Hz, 6 H), 3.98 (q, J = 6.6
Hz, 2 H), 1.38–1.28 (m, 9 H), 0.92 (t, J = 6.9 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 165.9, 164.3, 147.8, 142.2, 139.1,
138.9, 138.6, 136.2, 135.6, 128.8, 128.2, 125.1, 124.4, 124.1, 123.1,
122.9, 122.2, 121.9, 120.3, 118.8, 111.9, 111.2, 110.8, 110.2, 110.1,
109.4, 108.9 (Aromatic C), 98.6, 71.6, 61.5, 60.1, 49.1, 37.9, 37.8,
14.5, 13.8, 13.7 (Aliphatic C).
MS (positive mode): m/z = 774 [M + 2]+.
Anal. Calcd for C38H36Br2N4O4: C, 59.04; H, 4.70; N, 7.25. Found:
C, 59.15; H, 4.61; N, 7.36.
Dimethyl 1,3-Bis(6-bromo-9-ethyl-9H-carbazol-3-yl)-1,2,3,6-
tetrahydro-4,5-pyrimidinedicarboxylate (6j)
Yield: 0.610 g (82%); mp 110–112 °C.
IR (KBr): 2943, 1697, 1228, 605 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.89 (d, J = 1.7 Hz, 1 H), 7.73 (d,
J = 1.7 Hz, 1 H), 7.56 (s, 1 H), 7.41–7.36 (m, 3 H), 7.17 (d, J = 0.7
Hz, 2 H), 7.15–7.07 (m, 4 H), 4.92 (s, 2 H), 4.29 (s, 2 H), 4.19–4.14
(m, 4 H), 3.68 (s, 3 H), 3.42 (s, 3 H), 1.29–1.23 (m, 6 H).
13C NMR (100 MHz, CDCl3): d = 166.4, 164.8, 147.8, 142.1, 139.1,
139.0, 138.7, 136.3, 135.5, 128.9, 128.3, 124.9, 124.4, 124.1, 123.1,
123.0, 122.3, 122.1, 120.1, 118.5, 111.9, 111.2, 110.7, 110.2, 110.1,
109.4, 108.9 (Aromatic C), 98.2, 71.6, 52.5, 51.5, 48.9, 37.9, 37.8,
13.8, 13.7 (Aliphatic C).
(g) Boukouvalas, J.; Beltrán, P. P.; Lachance, N.; Côté, S.;
Maltais, F.; Pouliot, M. Synlett 2007, 219. (h) Gogoi, S.;
Argade, N. P. Synthesis 2008, 1455.
(5) (a) Senel, P.; Tichotova, L.; Votruba, I.; Buchta, V.; Spulak,
M.; Kunes, J.; Nobilis, M.; Krenk, O.; Pour, M. Bioorg. Med.
Chem. 2010, 18, 1988. (b) Milan, P.; Spulak, M.; Balsanek,
V.; Kunes, J.; Kubanova, P.; Buchta, V. Bioorg. Med. Chem.
2003, 11, 2843.
(6) (a) Weber, V.; Coudert, P.; Rubat, C.; Duroux, E.; Goyet, D.
V.; Gardette, D.; Bria, M.; Albuisson, E.; Leal, F.; Gramain,
J. C.; Couqueleta, J.; Madesclairea, M. Bioorg. Med. Chem.
2002, 10, 1647. (b) Pommier, A.; Stepanenko, V.;
Jarowicki, K.; Kocienski, P. J. J. Org. Chem. 2003, 68,
4008. (c) Boukouvalas, J.; Robichaud, J.; Maltais, F. Synlett
2006, 2480.
MS (negative mode): m/z = 742 [M+], 744 [M + 2]+.
Anal. Calcd for C36H32Br2N4O4: C, 58.08; H, 4.33; N, 7.53. Found:
C, 58.16; H, 4.37; N, 7.45.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
Acknowledgment
(7) (a) Bailly, F.; Queffelec, C.; Mbemba, G.; Franc, J.;
Mouscadet, O.; Pommery, N.; Pommery, J.; Henichart, J.;
Cotelle, P. Eur. J. Med. Chem. 2008, 43, 1222.
We gratefully acknowledge DST for financial assistance (Project
Number: SR/S1/OC–70/2008) and for providing the single-crystal
X-ray diffractometer facility in our school. S.R. thanks CSIR for a
Senior Research Fellowship.
(b) Gondela, E.; Walczak, K. Eur. J. Med. Chem. 2010, 45,
3993. (c) Steenackers, H. P.; Levin, J.; Janssens, J. C.;
Weerdt, A. D.; Balzarini, J.; Vanderleyden, J.; Vos, D. D.;
Keersmaecker, S. C. Bioorg. Med. Chem. 2010, 18, 5224.
(d) Teixeira, R. R.; Pinheiro, P.; Barbosa, L. C. A.; Carneiro,
J. W. M.; Forlani, G. Pest Manage. Sci. 2010, 66, 196.
(e) Boukouvalas, J.; McCann, L. C. Tetrahedron Lett. 2010,
51, 4636.
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Synthesis 2011, No. 20, 3307–3317 © Thieme Stuttgart · New York

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Multicomponent Synthesis of Heteroaryl-Substituted Carbazoles
3317
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(15) The crystal data of compounds 4a and 6b have been
deposited with the Cambridge Crystallographic Data Centre
as supplementary publication nos. CCDC 808976 (4a) and
808977 (6b). Copies of the data can be obtained, free of
charge, on application to CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK [Fax: +44(1223)336033; E-mail:
deposit@ccdc.cam.ac.uk or via http://www.ccdc.cam.ac.uk/
data_request/cif. Compound 4a: C27H23N3O6; unit cell
parameters: a = 8.5722(18) Å, b = 9.8231(18) Å,
c = 15.607(3) Å, a = 73.836(16)°, b = 74.258(18)°,
g = 76.080(17)°, space group P1. Compound 6b:
C36H34N4O4; unit cell parameters: a = 8.9790(6) Å,
b = 12.9073(8) Å, c = 15.8140(10) Å, a = 85.908(5)°,
b = 73.556(6)°, g = 76.731(6)°, space group P1.
(9) Abd, E. l.-FattahO.; Abbas, E. M. H.; Mohamed, N. A.; Abd-
Elmoez, S. I. Aust. J. Basic Appl. Sci. 2010, 4, 27.
Synthesis 2011, No. 20, 3307–3317 © Thieme Stuttgart · New York