One-pot, sequential four-component synthesis of novel heterocyclic [3.3.3] propellane derivatives at room temperature

Article abstract of DOI:10.1039/c8ra01648h

An efficient, one-pot, two-step, four-component reaction for the synthesis of propellane derivatives is described by the condensation reaction between acenaphthenequinone, malono derivatives, primary amines and β-ketoester or β-diketone derivatives in the presence of triethylamine in ethanol at room temperature. Using this procedure, all the products were obtained in good to excellent yields.

Full text of DOI:10.1039/c8ra01648h

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One-pot, sequential four-component synthesis of
novel heterocyclic [3.3.3] propellane derivatives at
room temperature†
Cite this: RSC Adv., 2018, 8, 14171
*
Maryam Beyrati and Alireza Hasaninejad
Received 24th February 2018
Accepted 9th April 2018
An efficient, one-pot, two-step, four-component reaction for the synthesis of propellane derivatives is
described by the condensation reaction between acenaphthenequinone, malono derivatives, primary
amines and b-ketoester or b-diketone derivatives in the presence of triethylamine in ethanol at room
temperature. Using this procedure, all the products were obtained in good to excellent yields.
DOI: 10.1039/c8ra01648h
rsc.li/rsc-advances
method for the synthesis of novel propellane derivatives via
a one-pot, sequential four-component condensation reaction
Introduction
between acenaphthoquinone (1), malono derivatives (2),
primary amines (4) and b-ketoester or b-diketone (5) derivatives
in the presence of triethylamine in ethanol at room temperature
(Scheme 1).
In modern organic chemistry, the improvement of reaction
efficiency, the reduction of waste, the avoidance of toxic
reagents and the responsible utilization of our resources have
become critical objectives.1,2 Multi-component reactions, are
useful tools for the synthesis of biologically and pharmacolog-
ically important compounds because of their environmentally
friendly, green characteristics and atom efficient.3–6 Therefore,
the design and application of multi-component reactions has
attracted great attention from research groups working in areas
such as biological, medicinal and organic chemistry.
Heterocyclic compounds occur commonly in nature and are
essential to life.7 These compounds have received considerable
attention in recent times due to their wide applications. Func-
tionalized nitrogen and oxygen-containing heterocycles are of
importance as they have various industrial, pharmaceutical and
biological applications.8–20
Propellanes are tricyclic compounds in which the three rings
are connected to a common C–C single bond.21 Nitrogen- and
oxygen-containing propellanes and their analogues constitute
the structural framework of many natural and non-natural
products such as periglaucine A, hasubanone, sinoacutine
and merrilactone A (Fig. 1).22,23 Propellanes due to their chal-
lenging framework and broad spectra of biological and phar-
macological activities, constitute an interesting class of
compounds in organic chemistry.24
Results and discussion
In the rst step, the reaction between acenaphthoquinone (1),
malononitrile (2a), ethyl acetoacetate (5a) and benzyl amine
(4c), as a model reaction, was investigated in the presence of
different molar ratios of Et3N in some solvents (5 mL) at room
temperature and the results are summarized in Table 1. For this
propose to a stirred mixture of acenaphthoquinone 1 (1 mmol)
and malononitrile 2a (1 mmol) in EtOH (5 mL) at room
temperature different amount of Et3N were added to form the
corresponding Knoevenagel adduct and then ethyl acetoacetate
5a (1 mmol) and benzyl amine 4c (1 mmol) were added to obtain
the corresponding product 6a. As it is shown in Table 1, higher
yield and shorter reaction time were obtained when the reaction
was carried out in the presence of 1 mmol of the Et3N in ethanol
at room temperature (Table 1, entry 4). It should be mention
that simultaneity of this four-component condensation reaction
was studied in the presence of 1 mmol Et3N in EtOH at room
temperature and we observed that benzyl amine has remained
Recently, there have been some reports about the synthesis
of propellane compounds from ninhydrin25–32 and acenaph-
thoquinone.32–34 In continuation of our research on the
synthesis of biologically important heterocycles and green
chemistry protocols,35–47 we report a simple and efficient
Department of Chemistry, Faculty of Sciences, Persian Gulf University, Bushehr,
7516913817, Iran. E-mail: a_hasaninejad@yahoo.com
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c8ra01648h
Fig. 1 Typical natural and biological products containing propellane
skeleton.
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cyanoacetate or ethyl cyanoacetate (compare 6b with 6p and 6l
with 6q). As it is shown in Table 2, benzyl amines bearing
electron-donating or -withdrawing substituents gave the desired
propellanes in high yields and in short reaction times and it
seems that when the methoxy group is placed on the aromatic
ring, reactivity is better than when the chlorine group is on the
ring. Moreover, the presence of 3,5-dimethyl group on the
aromatic ring has the best efficiency. Some aromatic amines
were also screened to carry out the four-component reaction by
this method and the results are listed in Table 2 (entries 6h–6j).
Generally, aliphatic amines are more reactive than aromatic
amines. Ortho-substituted anilines, whatever the nature of the
substituted groups, required a longer reaction period. For
instance, reaction of acenaphthenequinone, malononitrile and
2,6-dimethylaniline with ethyl acetoacetate gave the desired
product (6j) in 70% yield aer 3.1 h. Moreover, aliphatic amines
such as ethyl amine and butyl amine were used for the synthesis
of the corresponding product in excellent yields (Table 2, entries
6l–6o). In the same way, Some cyclic and acyclic 1.3-dicarbonyl
compounds were also screened to carry out the one pot four-
component reaction by this method and the results are listed
in Table 2. As it is shown in Table 2, aliphatic b-keto esters are
more reactive than aromatic b-keto esters (compare 6a and 6c)
and no products were obtained when cyclic 1.3-dicarbonyl
compounds were involved in this one-pot room temperature
reaction.
Scheme 1 The synthesis of propellane derivatives via the reaction
between acenaphthoquinone, malono derivatives, dicarbonyl
compounds and primary amines in the presence of Et3N in EtOH at
room temperature.
intact in this condition and the corresponding propellane was
not formed.
In the next step, the scope and efficiency of the process was
explored under the optimized conditions. For this purpose,
acenaphthoquinone was condensed with alkyl malonates,
aliphatic and aromatic amines and dicarbonyl compounds in
the presence of Et3N (1 mmol) to afford the corresponding
products 6. The structural diversity of reactants is summarized
in Fig. 2 and the results are displayed in Table 2.
The synthetic pathway for the synthesis of titled compounds
is consisting of two steps. At rst, compound 3 are obtained
from acenaphthoquinone 1 and alkyl malonates 2. Then, the
resulting products are treated with primary amines 4 and b-
dicarbonyl compounds 5 to afford the related propellane
derivatives as the desired products. As Table 2 indicates,
a variety of alkyl malonates, aliphatic and aromatic amines and
b-dicarbonyl compounds were successfully applied in this
process to afford the corresponding propellane derivatives as
novel compounds in good to excellent yields.
To demonstrate the generality and scope of this method,
malono derivatives, various acyclic b-dicarbonyl compounds
such as methyl acetoacetate, ethyl acetoacetate and ethyl ben-
zoylacetate were treated with a broad range of aliphatic and
aromatic amines in the presence of Et3N (1 mmol) in EtOH at
room temperature and the results are shown in Table 2. Use of
malononitrile leads to shorter reaction times and higher yields
compared to application of other alkylmalonates such as methyl
Table 1 Optimization of the reaction conditionsa
Amount of Et3N
(mmol)
Entry
Solvent
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
—
EtOH
EtOH
EtOH
EtOH
EtOH
H2O
5
5
5
—
45
87
91
91
70
60
85
40
55
45
0.1
0.5
1.0
1.5
1.0
1.0
1.0
1.0
1.0
1.0
1.2
1.2
2.0
4.0
1.5
4.0
4.0
40
DMF
MeOH
CHCl3
THF
9
10
11
CH3CN
a
Triethylamine (1.0 mmol) was added to
a stirred mixture of
acenaphthoquinone 1 (1 mmol), malononitrile 2a (1 mmol) in EtOH
(5 mL) at room temperature and aer about 10 min to form the
corresponding Knoevenagel adduct, then ethyl acetoacetate 5a (1
mmol) and benzyl amine 4c (1 mmol) were added to obtain the
corresponding product 6a. b Isolated yields.
Fig.
derivatives.
2 Diversity elements employed for synthesis of propellane
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Table 2 One-pot, sequential four component synthesis of propellane
derivatives in the presence of Et3N (1 mmol) in EtOH at room
temperature.a,b
Scheme 2 The proposed mechanism for the synthesis of propellane 6
in the presence of Et3N.
methylene of compound (2). Next, the formation of enamine (7)
occurs through condensation of amine (4) with dicarbonyl
compound (5). Then, the enamine (7) attacks to olen (3) in
a Michael addition to produce intermediate (8). Aer proton
transfer and tautomerization, intermediate (8) converts to
intermediate (10), through intramolecular cyclization by
nitrogen attack of enamine to carbonyl group. In this stage,
nucleophilic addition of amino group to C]O bond afforded
intermediate (10). Then, intramolecular O-cyclization and the
tautomerization of imino group to amino group lead to pro-
pellanes (6).
Experimental
All chemicals were purchased from Merck or Fluka chemical
1
companies. The H NMR (400 MHz) and 13C NMR (100 MHz)
were run on a Bruker Avance 400. Melting points were recorded
on a Stuart Scientic Apparatus SMP3 (UK) in open capillary
tubes. Elemental C, H and N analyses were performed using
a Costech CHNS-O elemental analyzer.
General procedure for the synthesis of propellane derivatives
6
Triethylamine (1.0 mmol) was added to a stirred mixture of
acenaphthoquinone 1 (1 mmol), malono derivatives 2 (1 mmol)
in EtOH (5 mL) and the reaction mixture was stirred to complete
the formation of related Knoevenagel adduct 3 (monitored by
TLC). Subsequently, dicarbonyl compound 5 (1 mmol) and
primary amine 4 (1 mmol) were added to this reaction mixture
at once and dropwise over 10 min, respectively and reacted at
room temperature for the appropriate amount of time (see
Table 2). Aer completion of the reaction conrmed by TLC, the
reaction mixture was ltered and washed with ethanol to afford
the pure product 6a–l.
a
Triethylamine (1.0 mmol) was added to
a stirred mixture of
acenaphthoquinone 1 (1 mmol), malono derivatives 2 (1 mmol) in
EtOH (5 mL) at room temperature to form the corresponding
Knoevenagel adduct (about 10–30 min), then dicarbonyl compound 5
(1 mmol) and primary amine 4 (1 mmol) were added to obtain the
desired product 6. b Isolated yields.
Ethyl-11-amino-7-benzyl-10-cyano-8-methyl-7H-6b,9a-(epox-
yetheno)acenaphtho[1,2-b]pyrrole-9-carboxylate 6a. White
powder, mp ¼ 249–251 ꢀC, 1H NMR (DMSO-d6, 400 MHz)
d (ppm): 1.45 (t, J ¼ 6.6 Hz, 3H), 2.25 (s, 3H), 4.04 (q, J ¼ 7.2 Hz,
2H), 4.54 (d, J ¼ 16.0 Hz, 1H), 4.60 (d, J ¼ 16.0 Hz, 1H), 7.57 (s,
2H), 7.66–7.71 (m, 3H), 7.73–7.81 (m, 4H), 7.89 (d, J ¼ 8.0 Hz,
2H), 8.04 (d, J ¼ 7.2 Hz, 2H). 13C NMR (DMSO-d6, 100 MHz)
The proposed mechanism for the synthesis of propellane
compounds 6 in the presence of Et3N is shown in Scheme 2.
Based on this mechanism, Et3N is effective catalyst for the
formation of olen (3) which readily prepares in situ by Knoe-
venagel condensation of acenaphthoquinone (1) with the active
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d (ppm): 14.4, 14.6, 58.1, 60.5, 61.2, 70.7, 79.9, 110.4, 118.4,
120.6, 121.0, 124.7, 125.8, 127.8, 129.2, 129.6, 132.0, 135.8,
136.3, 142.7, 147.2, 147.6, 147.7, 162.4, 166.5, 166.9, 168.0,
168.1. Anal. calcd for C28H23N3O3: C, 74.82; H, 5.16; N, 9.35%.
Found: C, 74.85; H, 5.14; N, 9.33%. IR (KBr) (nmax, cmꢁ1): 3358
and 3192 (NH2), 2193 (CN), 1687 (C]O), 1652 (OC]C).
9-Acetyl-11-amino-7-benzyl-8-methyl-7H-6b,9a-(epoxyetheno)ace-
naphtho[1,2-b]pyrrole-10-carbonitrile 6b. White powder, mp ¼ 250–
252 ꢀC, 1H NMR (DMSO-d6, 400 MHz) d (ppm): 2.32 (s, 3H), 2.36 (s,
3H), 4.74 (d, J ¼ 15.6 Hz, 1H), 4.99 (d, J ¼ 15.6 Hz, 1H), 7.45 (s, 2H),
7.63 (t, J ¼ 7.4 Hz, 2H), 7.69–7.71 (m, 2H), 7.73–7.77 (m, 3H), 7.85 (d,
J ¼ 7.6 Hz, 2H), 8.02 (d, J ¼ 8.0 Hz, 2H). 13C NMR (DMSO-d6, 100
MHz) d (ppm): 15.9, 30.3, 58.4, 59.1, 72.2, 79.8, 116.4, 116.6, 118.5,
120.4, 121.4, 121.6, 124.4, 124.9, 127.7, 128.9, 129.5, 131.9, 135.9,
136.3, 143.0, 148.0, 156.6, 157.1, 166.5, 167.2, 192.7. Anal. calcd for
C27H21N3O2: C, 77.31; H, 5.05; N, 10.02%. Found: C, 77.32; H,
5.02; N, 10.05%.
Ethyl-11-amino-7-(4-chlorobenzyl)-10-cyano-8-methyl-7H-6b,9a-
(epoxyetheno)acenaphtho[1,2-b]pyrrole-9-carboxylate 6f. White
powder, mp ¼ 249–251 ꢀC, 1H NMR (DMSO-d6, 400 MHz)
d (ppm): 1.44 (t, J ¼ 7.0 Hz, 3H), 2.25 (s, 3H), 4.11–4.17 (m, 2H),
4.42 (d, J ¼ 16.0 Hz, 1H), 4.48 (d, J ¼ 16.0 Hz, 1H), 7.77 (s, 2H),
7.85–7.91 (m, 2H), 7.92–7.96 (m, 3H), 7.99 (t, J ¼ 6.0 Hz, 1H),
8.08 (d, J ¼ 8.4 Hz, 2H), 8.23 (d, J ¼ 8.0 Hz, 2H). 13C NMR
(DMSO-d6, 100 MHz) d (ppm): 14.4, 14.6, 58.1, 60.6, 60.6, 70.7,
79.9, 110.4, 118.4, 120.6, 121.0, 124.7, 125.8, 127.8, 129.1, 129.6,
132.0, 135.8, 136.3, 142.7, 154.8, 155.1, 155.8, 157.5, 157.8,
166.6, 167.2, 167.3. Anal. calcd for C28H22ClN3O3: C, 69.49; H,
4.58; Cl, 7.33; N, 8.68%. Found: C, 69.50; H, 4.56; N, 8.70%.
9-Acetyl-11-amino-7-(3,5-dimethylbenzyl)-8-methyl-7H-6b,9a-
(epoxyetheno)acenaphtho[1,2-b]pyrrole-10-carbonitrile 6g. White
powder, mp ¼ 251–253 ꢀC, 1H NMR (DMSO-d6, 400 MHz)
d (ppm): 2.05 (s, 3H), 2.10 (s, 3H), 2.31 (s, 3H), 2.36 (s, 3H), 4.96
(d, J ¼ 16.0 Hz, 1H), 5.02 (d, J ¼ 16.0 Hz, 1H), 6.83 (d, J ¼ 7.6 Hz,
1H), 7.02 (t, J ¼ 7.4 Hz, 1H), 7.21–7.35 (m, 2H), 7.49 (d, J ¼
7.2 Hz, 2H), 7.58 (d, J ¼ 9.2 Hz, 1H), 7.79 (s, 2H), 7.85 (dd, J ¼
2.4 Hz, 8.8 Hz, 1H), 8.02 (d, J ¼ 2.4 Hz, 1H). 13C NMR (DMSO-d6,
100 MHz) d (ppm): 14.1, 20.2, 20.5, 30.3, 47.4, 59.3, 71.9, 79.7,
103.9, 108.4, 112.9, 116.9, 122.4, 123.4, 123.6, 125.4, 127.7,
128.4, 128.7, 134.1, 134.5, 137.2, 145.4, 152.4, 154.5, 158.4,
159.2, 167.5, 198.2. Anal. calcd for C29H25N3O2: C, 77.83; H,
5.63; N, 9.39%. Found: C, 77.80; H, 5.65; N, 9.41%.
Ethyl-11-amino-7-benzyl-10-cyano-8-phenyl-7H-6b,9a-(epox-
yetheno)acenaphtho[1,2-b]pyrrole-9-carboxylate
6c.
White
powder, mp ¼ 247–249 ꢀC, 1H NMR (DMSO-d6, 400 MHz)
d (ppm): 1.38 (t, J ¼ 7.0 Hz, 3H), (q, J ¼ 6.8 Hz, 2H), 4.92 (d, J ¼
16.0 Hz, 1H), 4.98 (d, J ¼ 16.0 Hz, 1H), 7.43 (t, J ¼ 7.4 Hz, 3H),
7.51 (t, J ¼ 7.0 Hz, 3H), 7.66 (s, 2H), 7.70–7.77 (m, 4H), 7.83 (d, J
¼ 6.8 Hz, 1H), 7.87 (d, J ¼ 7.2 Hz, 1H), 7.93 (d, J ¼ 8.0 Hz, 2H),
8.07 (d, J ¼ 8.0 Hz, 2H). 13C NMR (DMSO-d6, 100 MHz) d (ppm):
15.3, 43.6, 47.1, 47.2, 72.2, 79.9, 113.0, 116.3, 117.3, 117.5, 121.2,
123.4, 125.4, 125.7, 127.0, 127.7, 127.9, 128.3, 130.3, 134.5,
134.7, 135.6, 139.3, 147.4, 152.6, 155.4, 158.5, 158.5, 159.1,
159.3, 162.2, 168.1. Anal. calcd for C33H25N3O3: C, 77.48; H,
4.93; N, 8.21%. Found: C, 77.51; H, 4.91; N, 8.19%.
9-Acetyl-11-amino-8-methyl-7-phenyl-7H-6b,9a-(epoxyetheno)
acenaphtho[1,2-b]pyrrole-10-carbonitrile 6h. White powder, mp
1
ꢀ
¼ 247–249 C, H NMR (DMSO-d6, 400 MHz) d (ppm): 2.31 (s,
3H), 2.36 (s, 3H), 7.51–7.60 (m, 3H), 7.78–7.82 (m, 2H), 7.88 (s,
2H), 7.97 (dd, J ¼ 1.4 Hz, 7.8 Hz, 2H), 8.23 (dd, J ¼ 2.2 Hz, 8.6 Hz,
2H), 8.38 (d, J ¼ 2.4 Hz, 2H). 13C NMR (DMSO-d6, 100 MHz)
d (ppm): 15.8, 30.2, 57.2, 71.4, 79.8, 101.7, 109.6, 112.9, 117.2,
117.5, 123.2, 123.4, 124.6, 125.5, 127.6, 127.8, 128.9, 129.5,
132.8, 134.3, 136.4, 143.2, 152.6, 155.8, 158.9, 199.0. Anal. calcd
for C26H19N3O2: C, 77.02; H, 4.72; N, 10.36%. Found: C, 77.04;
H, 4.75; N, 10.32%.
9-Acetyl-11-amino-7-(4-methoxybenzyl)-8-methyl-7H-6b,9a-(epox-
yetheno)acenaphtho[1,2-b]pyrrole-10-carbonitrile
6d.
White
powder, mp ¼ 249–251 ꢀC, 1H NMR (DMSO-d6, 400 MHz)
d (ppm): 2.32 (s, 3H), 2.37 (s, 3H), 3.75 (s, 3H), 4.67 (d, J ¼
16.0 Hz, 1H), 4.78 (d, J ¼ 16.0 Hz, 1H), 7.35 (d, J ¼ 6.8 Hz, 2H),
7.55–7.59 (m, 2H), 7.77 (t, J ¼ 7.6 Hz, 2H), 7.84–7.89 (m, 2H),
8.09 (s, 2H), 8.17 (d, J ¼ 7.6 Hz, 2H). 13C NMR (DMSO-d6, 100
MHz) d (ppm): 15.9, 30.3, 57.6, 58.0, 58.4, 72.2, 79.9, 118.5,
120.4, 121.4, 121.7, 124.5, 124.9, 127.7, 128.9, 129.5, 131.9,
135.9, 136.3, 140.0, 140.1, 140.6, 140.8, 143.8, 166.6, 167.2,
168.6, 192.7. Anal. calcd for C28H23N3O3: C, 74.82; H, 5.16; N,
9.35%. Found: C, 74.79; H, 5.17; N, 9.38%. IR (KBr) (nmax, cmꢁ1):
3361 and 3101 (NH2), 2195 (CN), 1711 (C]O), 1644 (OC]C).
Ethyl-11-amino-10-cyano-7-(4-methoxybenzyl)-8-methyl-
7H-6b,9a-(epoxyetheno)acenaphtho[1,2-b]pyrrole-9-
9-Acetyl-11-amino-7-(4-methoxyphenyl)-8-methyl-7H-6b,9a-
(epoxyetheno)acenaphtho[1,2-b]pyrrole-10-carbonitrile
6i.
White powder, mp ¼ 252–254 ꢀC, 1H NMR (DMSO-d6, 400 MHz)
d (ppm): 2.22 (s, 3H), 2.93 (s, 3H), 3.74 (s, 3H), 7.53 (d, J ¼ 6.8 Hz,
2H), 7.67 (t, J ¼ 7.6 Hz, 1H), 7.89 (t, J ¼ 7.4 Hz, 1H), 7.99–8.04 (m,
4H), 8.08 (s, 2H), 8.33 8.02 (d, J ¼ 8.4 Hz, 2H). 13C NMR (DMSO-
d6, 100 MHz) d (ppm): 15.4, 30.0, 48.1, 57.5, 72.1, 79.2, 101.9,
110.0, 112.9, 117.1, 117.5, 122.5, 123.1, 124.6, 125.5, 129.4,
133.5, 134.2, 142.7, 152.5, 155.6, 158.8, 158.9, 166.1, 167.6,
177.6, 195.0. Anal. calcd for C27H21N3O3: C, 74.47; H, 4.86; N,
9.65%. Found: C, 74.43; H, 4.89; N, 9.67%.
carboxylate 6e. White powder, mp ¼ 251–253 ꢀC, 1H NMR
(DMSO-d6, 400 MHz) d (ppm): 0.57 (t, J ¼ 7.6 Hz, 3H), 1.90 (s,
3H), 3.10 (s, 3H), 3.45–3.49 (m, 1H), 3.79–3.82 (m, 1H), 4.77 (d, J
¼ 16.0 Hz, 1H), 5.03 (d, J ¼ 15.6 Hz, 1H), 7.57 (s, 2H), 7.66–7.71
(m, 2H), 7.73–7.76 (m, 2H), 7.79 (t, J ¼ 6.0 Hz, 2H), 7.88 (d, J ¼
8.0 Hz, 2H), 8.03 (d, J ¼ 7.6 Hz, 2H). 13C NMR (DMSO-d6, 100
MHz) d (ppm): 14.4, 14.6, 47.5, 69.4, 70.0, 73.1, 73.3, 79.7, 106.1,
116.2, 117.6, 121.2, 125.1, 127.0, 127.7, 127.9, 128.2, 130.2,
134.7, 135.5, 139.3, 147.4, 158.7, 159.3, 159.8, 160.7, 162.3,
165.0, 168.8. Anal. calcd for C29H25N3O4: C, 72.64; H, 5.25; N,
8.76%. Found: C, 72.62; H, 5.23; N, 8.79%.
Ethyl-11-amino-10-cyano-7-(2,6-dimethylphenyl)-8-methyl-7H-
6b,9a-(epoxyetheno)acenaphtho[1,2-b]pyrrole-9-carboxylate 6j.
White powder, mp ¼ 255–257 ꢀC, 1H NMR (DMSO-d6, 400 MHz)
d (ppm): 1.35 (t, J ¼ 7.2 Hz, 3H), 2.21 (s, 3H), 2.30 (s, 3H), 2.33 (s,
3H), 3.31–3.34 (m, 2H), 7.35 (d, J ¼ 6.8 Hz, 2H), 7.55–7.59 (m,
2H), 7.77 (t, J ¼ 7.6 Hz, 2H), 7.84–7.89 (m, 2H), 8.10 (s, 2H), 8.17
(d, J ¼ 7.6 Hz, 1H). 13C NMR (DMSO-d6, 100 MHz) d (ppm): 13.6,
14.6, 21.4, 21.7, 59.6, 60.2, 72.0, 79.8, 104.3, 108.9, 112.8, 112.9,
116.8, 117.0, 121.5, 123.7, 124.1, 125.3, 125.6, 128.4, 133.9,
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134.3, 135.2, 144.6, 152.3, 154.2, 167.6, 170.9, 179.4. Anal. calcd ¼ 7.3 Hz, 2H), 7.46 (s, 2H), 7.63 (t, J ¼ 7.6 Hz, 1H), 7.70 (d, J ¼
for C29H25N3O3: C, 75.14; H, 5.44; N, 9.07%. Found: C, 75.10; H, 7.2 Hz, 1H), 7.75 (t, J ¼ 7.0 Hz, 1H), 7.85 (d, J ¼ 7.2 Hz, 2H), 8.01
5.42; N, 9.12%.
(d, J ¼ 8.0 Hz, 1H). 13C NMR (DMSO-d6, 100 MHz) d (ppm): 15.2,
Ethyl-11-amino-7-(4-chlorophenyl)-10-cyano-8-methyl-7H- 15.9, 23.7, 29.9, 30.3, 58.4, 59.5, 72.2, 79.9, 118.5, 120.4, 121.4,
6b,9a-(epoxyetheno)acenaphtho[1,2-b]pyrrole-9-carboxylate
121.6, 124.4, 124.9, 127.7, 128.9, 129.5, 131.9, 135.9, 136.3,
1
ꢀ
6k. White powder, mp ¼ 251–253 C, H NMR (DMSO-d6, 400 166.6, 167.2, 192.7. Anal. calcd for C24H23N3O2: C, 74.78; H,
MHz) d (ppm): 1.19 (t, J ¼ 7.2 Hz, 3H), 2.00 (s, 3H), 4.04 (q, J ¼ 6.01; N, 10.90%. Found: C, 74.75; H, 6.03; N, 10.92%.
7.2 Hz, 2H), 7.56 (d, J ¼ 8.8 Hz, 1H), 7.65 (d, J ¼ 7.2 Hz, 1H), 7.72
Ethyl-9-acetyl-11-amino-7-benzyl-8-methyl-7H-6b,9a-(epox-
(t, J ¼ 7.6 Hz, 1H), 7.77 (s, 2H), 7.84 (dd, J ¼ 2.4 Hz, 8.8 Hz, 1H), yetheno)acenaphtho[1,2-b]pyrrole-10-carboxylate 6p. White
7.90 (t, J ¼ 7.6 Hz, 1H), 8.03–8.06 (m, 3H), 8.37 (d, J ¼ 8.0 Hz, powder, mp ¼ 249–251 ꢀC, 1H NMR (DMSO-d6, 400 MHz)
2H). 13C NMR (DMSO-d6, 100 MHz) d (ppm): 13.7, 14.6, 59.8, d (ppm): 0.83 (t, J ¼ 7.0 Hz, 3H), 2.10 (s, 3H), 2.44 (s, 3H), 3.80 (q,
60.2, 71.9, 79.2, 103.0, 108.9, 113.1, 116.9, 119.8, 123.5, 125.3, J ¼ 7.3 Hz, 2H), 4.84 (d, J ¼ 16.0 Hz, 1H), 5.12 (d, J ¼ 16.0 Hz,
126.1, 134.1, 136.2, 142.4, 151.2, 152.4, 155.1, 158.7, 159.3, 1H), 7.42 (s, 2H), 7.64–7.67 (m, 2H), 7.70–7.74 (m, 3H), 7.84 (d, J
167.2, 167.7, 180.2. Anal. calcd for C27H20ClN3O3: C, 69.01; H, ¼ 6.4 Hz, 3H), 7.99–8.06 (m, 3H). 13C NMR (DMSO-d6, 100 MHz)
4.29; Cl, 7.54; N, 8.94%. Found: C, 69.05; H, 4.26; N, 8.92%.
d (ppm): 15.0, 15.1, 31.9, 58.7, 59.4, 71.8, 72.5, 80.0, 118.2, 118.4,
Ethyl-11-amino-10-cyano-7-ethyl-8-methyl-7H-6b,9a-(epox- 120.1, 120.8, 124.0, 124.1, 125.6, 127.5, 128.6, 129.1, 131.8,
yetheno)acenaphtho[1,2-b]pyrrole-9-carboxylate 6l. White 136.2, 136.6, 142.9, 163.4, 166.1, 166.7, 167.3, 167.9, 195.3. Anal.
powder, mp ¼ 250–252 ꢀC, 1H NMR (DMSO-d6, 400 MHz) calcd for C29H26N2O4: C, 74.66; H, 5.62; N, 6.00%. Found: C,
d (ppm): 0.76 (t, J ¼ 7.2 Hz, 3H), 1.44 (t, J ¼ 7.0 Hz, 3H), 2.25 (s, 74.68; H, 5.59; N, 6.02%. IR (KBr) (nmax, cmꢁ1): 3359 and 3161
3H), 2.81 (q, J ¼ 7.0 Hz, 2H), 4.30 (q, J ¼ 7.0 Hz, 2H), 7.57 (s, 2H), (NH2), 1738 (C]O), 1667 (C]O), 1639 (OC]C).
7.66–7.71 (m, 1H), 7.72–7.76 (m, 2H), 7.79 (t, J ¼ 6.0 Hz, 1H),
9-Ethyl-10-methyl-11-amino-7-ethyl-8-methyl-7H-6b,9a-(epox-
7.88 (d, J ¼ 8.4 Hz, 1H), 8.03 (d, J ¼ 8.0 Hz, 1H). 13C NMR yetheno)acenaphtho[1,2-b]pyrrole-9,10-dicarboxylate 6q. White
(DMSO-d6, 100 MHz) d (ppm): 7.9, 14.4, 14.6, 58.1, 58.6, 60.5, powder, mp ¼ 247–249 ꢀC, 1H NMR (DMSO-d6, 400 MHz)
70.7, 79.9, 110.4, 118.4, 120.6, 121.0, 124.7, 125.8, 127.8, 129.1, d (ppm): 0.86 (t, J ¼ 7.0 Hz, 3H), 1.18 (t, J ¼ 7.2 Hz, 3H), 2.00 (s,
129.6, 132.0, 135.8, 136.3, 142.7, 167.3, 168.1. Anal. calcd for 3H), 3.22 (s, 3H), 3.81 (q, J ¼ 7.1 Hz, 2H), 4.04 (q, J ¼ 7.2 Hz, 2H),
C
23H21N3O3: C, 71.30; H, 5.46; N, 10.85%. Found: C, 71.28; H, 7.38 (s, 2H), 7.59 (t, J ¼ 7.6 Hz, 1H), 7.63 (d, J ¼ 7.2 Hz, 1H), 7.69
5.44; N, 10.88%. IR (KBr) (nmax, cmꢁ1): 3405 and 3278 (NH2), (t, J ¼ 6.6 Hz, 1H), 7.81 (d, J ¼ 8.4 Hz, 1H), 7.99 (d, J ¼ 7.6 Hz,
2197 (CN), 1663 (C]O), 1639 (OC]C).
1H), 8.08 (d, J ¼ 6.8 Hz, 1H). 13C NMR (DMSO-d6, 100 MHz)
9-Acetyl-11-amino-7-ethyl-8-methyl-7H-6b,9a-(epoxyetheno)ace- d (ppm): 14.5, 14.6, 15.1, 58.6, 60.1, 60.9, 61.7, 70.8, 79.8, 120.1,
naphtho[1,2-b]pyrrole-10-carbonitrile 6m. White powder, mp ¼ 124.0, 124.2, 126.0, 127.6, 128.5, 129.0, 131.7, 136.1, 136.6,
1
251–253 ꢀC, H NMR (DMSO-d6, 400 MHz) d (ppm): 0.86 (t, J ¼ 142.7, 164.6, 165.0, 166.2, 166.9. Anal. calcd for C24H24N2O5: C,
7.0 Hz, 3H), 2.32 (s, 3H), 2.36 (s, 3H), 3.81 (q, J ¼ 7.1 Hz, 2H), 68.56; H, 5.75; N, 6.66%. Found: C, 68.58; H, 5.77; N, 6.63%. IR
7.46 (s, 2H), 7.63 (t, J ¼ 7.6 Hz, 1H), 7.70 (d, J ¼ 7.2 Hz, 1H), 7.75 (KBr) (nmax, cmꢁ1): 3412 and 3249 (NH2), 1736 (C]O), 1675 (C]
(t, J ¼ 7.0 Hz, 1H), 7.85 (d, J ¼ 7.6 Hz, 2H), 8.01 (d, J ¼ 7.6 Hz, O), 1642 (OC]C).
1H). 13C NMR (DMSO-d6, 100 MHz) d (ppm): 15.3, 15.9, 30.3,
58.4, 59.0, 72.2, 79.9, 118.5, 120.4, 121.4, 121.6, 124.4, 124.9,
127.7, 128.9, 129.5, 131.9, 135.9, 136.3, 143.0, 167.2, 192.7. Anal.
Conclusions
calcd for C22H19N3O2: C, 73.93; H, 5.36; N, 11.76%. Found: C, In conclusion, we have reported a highly efficient method for
73.92; H, 5.39; N, 11.73%.
the synthesis of biologically important propellane derivatives
Ethyl-11-amino-7-butyl-10-cyano-8-methyl-7H-6b,9a-(epox-
via a one-pot, sequential four-component condensation reac-
yetheno)acenaphtho[1,2-b]pyrrole-9-carboxylate 6n. White tion presence of triethylamine in ethanol at room temperature.
powder, mp ¼ 247–249 ꢀC, 1H NMR (DMSO-d6, 400 MHz) High atom-economy, simple procedure in the excellent yields,
d (ppm): 0.95 (t, J ¼ 7.2 Hz, 3H), 1.44 (t, J ¼ 7.2 Hz, 3H), 1.80– easy workup procedure, mild reaction conditions and metal-
1.92 (m, 4H), 2.25 (s, 3H), 2.98 (t, J ¼ 6.4 Hz, 2H), 4.32 (q, J ¼ catalyst free are the main advantages of this method.
7.2 Hz, 2H), 7.57 (s, 2H), 7.67 (t, J ¼ 7.6 Hz, 1H), 7.71 (d, J ¼
7.6 Hz, 1H), 7.75 (d, J ¼ 6.4 Hz, 1H), 7.79 (t, J ¼ 6.4 Hz, 1H), 7.88
Conflicts of interest
(d, J ¼ 8.0 Hz, 1H), 8.03 (d, J ¼ 8.0 Hz, 1H). 13C NMR (DMSO-d6,
100 MHz) d (ppm): 12.7, 14.4, 14.6, 19.0, 26.2, 55.1, 58.1, 60.5, There are no conicts to declare.
70.7, 79.9, 110.4, 118.4, 120.6, 121.0, 124.7, 125.8, 127.8, 129.1,
129.6, 132.0, 135.8, 136.3, 142.7, 167.3, 168.1. Anal. calcd for
Acknowledgements
C
25H25N3O3: C, 72.27; H, 6.06; N, 10.11%. Found: C, 72.30; H,
6.05; N, 10.08%. IR (KBr) (nmax, cmꢁ1): 3389 and 3179 (NH2), The authors thank Persian Gulf University Research Councils
2203 (CN), 1661 (C]O), 1635 (OC]C).
for the nancial support of this work.
9-Acetyl-11-amino-7-butyl-8-methyl-7H-6b,9a-(epoxyetheno)
acenaphtho[1,2-b]pyrrole-10-carbonitrile 6o. White powder, mp
¼ 248–250 ꢀC, 1H NMR (DMSO-d6, 400 MHz) d (ppm): 0.84 (t, J ¼
7.2 Hz, 3H), 1.05–1.12 (m, 4H), 2.31 (s, 3H), 2.36 (s, 3H), 2.96 (q, J
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