Isocyanide-catalyzed reaction of tetracyanoethylene and activated 1,3-dicarbonyl CH-acid compounds: A rapid and efficient synthesis of pyran annulated heterocyclic systems

Article abstract of DOI:10.1080/00397910701749757

An isocyanide-catalyzed reaction between tetracyanoethylene and various activated CH-acid compounds to afford the corresponding pyran annulated heterocyclic ring systems, in high yield at room temperature within a few minutes, is described. To the best of our knowledge, this is the first example in which isocyanide functions as only a catalyst but not a reagent. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701749757

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Isocyanide‐Catalyzed Reaction of
Tetracyanoethylene and Activated
1,3‐Dicarbonyl CH‐Acid Compounds: A Rapid
and Efficient Synthesis of Pyran Annulated
Heterocyclic Systems
a
a
a
Ahmad Shaabani , Ali Hossein Rezayan , Afshin Sarvary & Abbas Rahmati
a
a
Department of Chemistry, Shahid Beheshti University, Tehran, Iran
Published online: 18 Jan 2008.
To cite this article: Ahmad Shaabani , Ali Hossein Rezayan , Afshin Sarvary & Abbas Rahmati (2008):
Isocyanide‐Catalyzed Reaction of Tetracyanoethylene and Activated 1,3‐Dicarbonyl CH‐Acid Compounds:
A Rapid and Efficient Synthesis of Pyran Annulated Heterocyclic Systems, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 38:2, 274-281
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Synthetic Communications , 38: 274–281, 2008
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701749757
Isocyanide-Catalyzed Reaction
of Tetracyanoethylene and Activated 1,3-
Dicarbonyl CH-Acid Compounds: A Rapid
and Efficient Synthesis of Pyran Annulated
Heterocyclic Systems
Ahmad Shaabani, Ali Hossein Rezayan, Afshin Sarvary,
and Abbas Rahmati
Department of Chemistry, Shahid Beheshti University, Tehran, Iran
Abstract: An isocyanide-catalyzed reaction between tetracyanoethylene and various
activated CH-acid compounds to afford the corresponding pyran annulated hetero-
cyclic ring systems, in high yield at room temperature within a few minutes, is
described. To the best of our knowledge, this is the first example in which isocyanide
functions as only a catalyst but not a reagent.
Keywords: CH-acid, isocyanide-catalyzed reaction, pyrans, tetracyanoethylene
INTRODUCTION
Pyrans and their derivatives are of considerable interest because of their
[1]
wide range of biological properties, such as spasmolytic, diuretic, anticoa-
gulant, and anti-cancer, anti-anaphylactic activity.
[2–6]
In addition, they can
be used as cognitive enhancers for the treatment of neurodegenerative
diseases, including Alzheimer’s disease, amyotrophic lateral sclerosis,
Huntington’s disease, Parkinson’s disease, AIDS-associated dementia, and
Received December 12, 2006
Address correspondence to Ahmad Shaabani, Department of Chemistry, Shahid
Beheshti University, P. O. Box 19396-4716, Tehran, Iran. E-mail: a-shaabani@cc.
sbu.ac.ir
2
74

Isocyanide as Catalyst
275
Scheme 1.
Down syndrome, as well as for the treatment of schizophrenia and
[
myoclonus. 4H-Pyrans also constitute the structural unit of a series of
7]
[
8,9]
natural products.
In view of our general interest in isocyanide-based multicomponent
[10]
reactions (MCRs) involving zwitterionic species,
we were intrigued by
the possibility trapping of the 1,3-zwitterionic intermediate generated from
isocyanide and tetracyanoethylene (TCNE) with activated CH-acids. We did
not observe the expected MCR product 4; instead, the reaction afforded the
corresponding pyran annulated heterocyclic systems (PAHS) with isocyanide
playing a catalyst role in the reaction between TCNE and activated CH-acids.
To the best of our knowledge, an isocyanide-catalyzed reaction is not known
(Scheme 1).
RESULTS AND DISCUSSION
In an initial experiment, the reaction of TCNE 1 with 5,5-dimethylcyclohex-
ane-1,3-dione 2 in the presence of cyclohexyl isocyanide 3 (10 mol%) in
CH Cl afforded the 2-amino-5,6,7,8-tetrahydro-7,7-dimethyl-5-oxochro-
2
2
mene-3,4,4-tricarbonitrile 5a in 89% yield. Similar reactivity was observed
with other cyclic-1,3-dicarbonyl compounds such as cyclopentane-1,3-dione
and cyclohexane-1,3-dione, and results are summarized in Table 1.
All of the products are new compounds that were characterized by IR,
1
13
H NMR, and C NMR spectra. The mass spectra of products displayed
molecular ion peaks at the appropriate m/z values.
1
The H NMR spectrum of 5a exhibited three singlets identified as one
methyl (at d ¼ 1.04 ppm) and two methylene (at d ¼ 2.44 and 2.59 ppm)

2
76
A. Shaabani et al.
Table 1. Reaction of TCNE with various b-dicarbonyl activated CH-acids in the
presence of a catalytic amount of cyclohexyl isocyanide
Entry
1
CH-acid
Product
Yield (%)
89
Time (min)
30
2
3
4
95
90
79
10
30
40
5
6
82
84
20
15
7
84
50
1
13
protons. The NH protons resonate at d ¼ 8.40 ppm. The H decoupled
C
2
NMR spectrum of 5a showed 12 distinct resonances, in agreement with the
suggested structures.
To illustrate the role of isocyanide, the reaction of TCNE 1 and 5,5-
dimethylcyclohexane-1,3-dione 2 was studied in the absence of cyclohexyl
isocyanide. Only a trace yield of the desired product was obtained under
similar conditions after 30 min.
The reaction of 1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione with
TCNE 1 in the presence of isocyanide in CH Cl at room temperature also
afforded similar pyran annulated heterocyclic systems (Table 1, entry 4).
2
2

Isocyanide as Catalyst
277
In view of the success of these reactions, we explored the use of
-hydroxy-6-methyl-2H-pyran-2-one, 4-hydroxy-2H-chromen-2-one, and
-hydroxy-1-methylquinolin-2(1H)-one as activated CH-acid in this
4
4
reaction. Treatment of 4-hydroxy-6-methyl-2H-pyran-2-one, 4-hydroxy-2H-
chromen-2-one, or 4-hydroxy-1-methylquinolin-2(1H)-one with TCNE 1 in
the presence of isocyanide in CH Cl at room temperature led to the
2
2
formation of the corresponding pyran annulated heterocyclic systems in
high yields (Table 1, entries 5–7).
A mechanistic rationalization for the reaction is provided in Scheme 2.
In conclusion, we have devised a rapid and very efficient isocyanide-
catalyzed approach for the synthesis of pyran annulated heterocyclic ring
systems under neutral and mild reaction conditions with excellent yields. To
the best of our knowledge, this is the first example in which isocyanide
functions as only a catalyst, but not a reagent.
EXPERIMENTAL
Melting points were measured on an Electrothermal 9200 apparatus. IR
spectra were recorded on a FT-IR 102MB BOMEM apparatus. Mass spectra
were recorded on a Finnigan-MAT 8430 mass spectrometer operating at an
1
13
ionization potential of 70 eV. H and C NMR spectra were recorded on a
Scheme 2.

2
78
A. Shaabani et al.
1
13
Bruker DRX-300 Avance spectrometer at 300.13 and 75.47 MHz. H and
NMR spectra were obtained on solutions in CDCl and DMSO-d .
C
3
6
Typical Experimental Procedure: Preparation of 2-Amino-5,6,7,8-
tetrahydro-7,7-dimethyl-5-oxochromene-3,4,4-tricarbonitrile (5a)
A mixture of cyclohexyl isocyanide (0.011 g, 10 mol%) in CH Cl (2 mL)
2
2
was added dropwise to a magnetically stirred solution of tetracyanoethylene
0.128 g, 1.0 mmol) and 5,5-dimethylcyclohexane-1,3-dione (0.140 g,
(
1
3
.0 mmol) in CH Cl (15 mL) at room temperature and was stirred for
2 2
0 min. After completion of the reaction, the solvent was removed under
vacuum, and the residue was crystallized from CH Cl /n-hexane 1:2 to
2
2
yield 0.238 g of 5a as a pink powder (89%). Mp 198–2008C. IR (KBr)
2
1
1
nmax, cm ): 3370, 3345 (NH ), 2209 (CN), 1681 (C 55 O). H NMR
(
2
(
300 MHz, DMSO-d ): dH (ppm) 1.04 (s, 6H, 2CH ), 2.44 (s, 2H, CH ),
6
3
2
1
3
.59 (s, 2H, CH ), 8.40 (s, 2H, NH ). C NMR (75 MHz, DMSO-d ): d
2 2 6 C
2
(
ppm) 13.76, 18.58, 27.18, 30.07, 31.77, 49.69, 101.91, 113.74 (CN),
þ
1
16.16 (CN), 158.83, 166.36, 193.94 (C 55 O). MS, m/z (%): 268 (M , 20),
242 (40), 226 (100), 185 (55), 157 (30), 129 (35), 83 (45), 57 (50), 41 (60).
Anal. calcd. for C H N O : C, 62.68; H, 4.51; N, 20.88. Found: C, 62.50;
H, 4.45; N, 20.69.
1
4 12 4 2
Data
2-Amino-6,7-dihydro-5-oxocyclopenta[b]pyran-3,4,4(5H)-
tricarbonitrile (5b)
2
1
Cream powder (0.215 g, 95%): mp 178–1808C. IR (KBr) (nmax, cm ): 3382,
1
360 (NH ), 2201 (CN), 1666 (C 55 O). H NMR (300 MHz, DMSO-d ): d
2 6 H
3
1
3
(
ppm) 2.61 (br, 2H, CH ), 2.84 (br, 2H, CH ), 8.60 (s, 2H, NH
2).
C NMR
75 MHz, DMSO-d ) dc 19.06, 29.43, 33.69, 49.26, 105.46, 113.09 (CN),
2
2
(
6
þ
1
16.68 (CN), 161.08, 180, 198.85 (C 55 O). MS, m/z (%): 226 (M , 30), 200
(
25), 184 (20), 78 (20), 57 (60), 41(100). Anal. calcd. for C H N O : C,
11 6 4 2
58.41; H, 2.67; N, 24.77. Found: C, 58.27; H, 2.58; N, 23.92.
2-Amino-5,6,7,8-tetrahydro-5-oxochromene-3,4,4-tricarbonitrile (5c)
2
1
Pink powder (0.216 g, 90%): mp 196–1988C. IR (KBr) (nmax, cm ): 3372,
1
355 (NH ), 2208 (CN), 1668 (C 55 O). H NMR (300 MHz, DMSO-d ): d
2 6 H
3
(
ppm) 1.99 (br, 2H, CH ), 2.49 (br, 2H, CH ), 2.64 (br, 2H, CH ), 8.36
2 2 2
1
3
(
s, 2H, NH2). C NMR (75 MHz, DMSO-d ): d (ppm) 19.53, 27.40,
6 C
3
1
0.71, 35.92, 50.29, 103.10, 114.37 (CN), 116.67 (CN), 159.13, 168.83,
þ
94.58 (C 55 O). MS, m/z (%): 240 (M , 25), 214 (100), 184 (90), 158 (40),

Isocyanide as Catalyst
279
1
3
20 (35), 88 (30), 66 (65), 39 (85). Anal. calcd. for C H N O : C, 60.00; H,
1
2 8 4 2
.36; N, 23.32. Found: C, 60.10; H, 3.32; N, 23.14.
6-Amino-1,2,3,4-tetrahydro-1,3-dimethyl-2,4-dioxopyrano[3,2-
d]pyrimidine-7,8,8-tricarbonitrile (5d)
2
1
Light green powder (0.224 g, 79%): mp 2108C (dec). IR (KBr) (n , cm ):
3
max
1
351, 3340 (NH ), 2214 (CN), 1718 (C 55 O), 1685 (C 55 O). H NMR
2
(
300 MHz, DMSO-d ): d (ppm) 3.23 (s, 3H, CH ), 3.29 (s, 3H, CH ), 8.67
6 H 3 3
1
s, 2H, NH2). C NMR (75 MHz, DMSO-d ): d (ppm) 28.48, 30.02,
3
(
6 C
3
2.08, 50.28, 78.75, 114.07 (CN), 116.23 (CN), 149.72, 152.94, 158.81
þ
(
(
C 55 O), 159.62 (C 55 O). MS, m/z (%): 268 (M 2 16, 20), 242 (25), 209
30), 181 (20), 154 (70), 132 (25), 105 (60), 78 (60), 56 (100), 41 (75).
Anal. calcd. for C H N O : C, 50.71; H, 2.84; N, 29.57. Found: C, 50.13;
1
2 8 6 3
H, 2.75; N, 29.32.
2-Amino-7-methyl-5-oxopyrano[4,3-b]pyran-3,4,4(5H)-tricarbonitrile (5e)
2
1
Cream powder (0.208 g, 82%): mp 2038C (dec). IR (KBr) (nmax, cm ): 3382,
1
366 (NH ), 2215 (CN), 1729 (C 55 O). H NMR (300 MHz, DMSO-d ): d
2 6 H
3
1
3
(
(
(
ppm) 2.33 (s, 3H, CH ), 6.48 (s, 1H, olefin), 8.52 (s, 2H, NH ). C NMR
3 2
75 MHz, DMSO-d ): dC (ppm) 20.06, 31.70, 49.77, 89.38, 98.94, 113.53
6
CN), 116.63 (CN), 159.30, 160.15, 160.68, 167.72 (C 55 O). MS, m/z (%):
þ
228 (M 2 26, 20), 200 (25), 85 (95), 69 (30), 43 (100). Anal. calcd. for
C H N O : C, 56.70; H, 2.38; N, 22.04. Found: C, 56.35; H, 2.23; N, 21.89.
1
2 6 4 3
2
-Amino-5-oxopyrano[3,2-c]chromene-3,4,4(5H)-tricarbonitrile (5f)
2
1
White powder (0.244 g, 84%): mp 2208C (dec). IR (KBr) (nmax, cm ): 3355,
1
345 (NH ), 2213 (CN), 1712 (C 55 O). H NMR (300 MHz, DMSO-d ): d
2 6 H
3
1
3
(
ppm) 7.60–7.87 (m, 4H, arom), 8.69 (s, 2H, NH2). C NMR (75 MHz,
DMSO-d ) dC (ppm) 32.19, 50.03, 92.49, 112.57 (CN), 113.48 (CN),
6
1
16.52, 117.55, 123.78, 125.86, 135.71, 153.14, 156.43, 158.69, 159.10
þ
(C 55 O). MS, m/z (%): 264 (M 2 26, 35), 236 (20), 150 (40), 121 (100),
9
1
2 (35), 65 (20), 45 (20). Anal. calcd. for C H N O : C, 62.07; H, 2.08; N,
15 6 4 3
9.3. Found: C, 61.33; H, 2.09; N, 19.02.
2-Amino-5,6-dihydro-6-methyl-5-oxopyrano[3,2-c]quinoline-3,4,4-
tricarbonitrile (5g)
2
1
White powder (0.254 g, 84%): mp 2198C (dec). IR (KBr) (nmax, cm ): 3375,
1
3
360 (NH ), 2203 (CN), 1676 (C 55 O). H NMR (300 MHz, DMSO-d ): d
2 6
H
1
3
(
ppm) 3.69 (s, 3H, CH ), 7.45–7.96 (m, 4H, arom), 8.53 (s, 2H, NH ).
3
C
2

2
80
A. Shaabani et al.
NMR (75 MHz, DMSO-d ) d (ppm) 30.22, 32.57, 50.34, 96.56, 112.09 (CN),
6
C
1
1
1
2
14.27 (CN), 116.07, 116.95, 123.46, 123.55, 134.40, 140.00, 152.20, 158.59,
þ
59.52 (C 55 O). MS, m/z (%): 304 (MH , 10), 285 (50), 276 (100), 249 (40),
50 (30), 104 (30), 84 (25), 49 (70). Anal. calcd. for C H N O : C, 63.37; H,
.99; N, 23.09. Found: C, 62.09; H, 2.87; N, 22.05.
1
6 9 5 2
ACKNOWLEDGMENT
We gratefully acknowledge the financial support from the Research Council
of Shahid Beheshti University.
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