1,8-diazabicyclo[5.4.0]undec-7-ene: A highly efficient catalyst for one-pot synthesis of substituted tetrahydro-4h-chromenes, tetrahydro[b]pyrans, pyrano[d]pyrimidines, and 4h-pyrans in aqueous medium

Article abstract of DOI:10.1002/jhet.1507

We have reported 1,8-diazabicyclo[5.4.0]undec-7-ene catalyzed one-pot synthesis of tetrahydro-4H-chromenes, tetrahydro[b]pyrans, pyrano[d]pyrimidines and 4H-pyrans from aldehydes, active methylene compounds malononitrile/ethyl cyanocacetate and activated C-H acids such as dimedone, 1,3-cyclohexanedione, 1,3-cyclopentanedione, 1,3-dimethylbarbituric acid, and ethyl acetoacetate in water under reflux. The attractive features of this process are mild reaction conditions, reusability of the reaction media, short reaction times, easy isolation of products, and excellent yields. Copyright 2013 HeteroCorporation

Full text of DOI:10.1002/jhet.1507

Month 2013 1,8-Diazabicyclo[5.4.0]undec-7-ene: A Highly Efficient Catalyst for One-
Pot Synthesis of Substituted Tetrahydro-4H-chromenes, Tetrahydro[b]
pyrans, Pyrano[d]pyrimidines, and 4H-Pyrans in Aqueous Medium
*
Jitender M. Khurana, Bhaskara Nand, and Pooja Saluja
Department of Chemistry, University of Delhi, Delhi-110007, India
*
E-mail: jmkhurana@chemistry.du.ac.in
Received July 7, 2011
DOI 10.1002/jhet.1507
Published online 00 Month 2013 in Wiley Online Library (wileyonlinelibrary.com).
O
O
R
O
R2
R2
R1
R2
R2
O
O
NH2
R
O
O
CN
O
NH2
CH3
N
O
CN
R1
DBU
O
OH
+
CH3
R
H
Water/reflux
N
NH2
CN
O
N
O
H3C
R1 = CN, COOEt
O
N
H3C
O
O
O
R
R
C2H5
CN
O
O
O
O
NH2
We have reported 1,8-diazabicyclo[5.4.0]undec-7-ene catalyzed one-pot synthesis of tetrahydro-4H-
chromenes, tetrahydro[b]pyrans, pyrano[d]pyrimidines and 4H-pyrans from aldehydes, active methylene
compounds malononitrile/ethyl cyanocacetate and activated C–H acids such as dimedone, 1,3-cyclohexanedione,
1,3-cyclopentanedione, 1,3-dimethylbarbituric acid, and ethyl acetoacetate in water under reflux. The attractive
features of this process are mild reaction conditions, reusability of the reaction media, short reaction times, easy
isolation of products, and excellent yields.
J. Heterocyclic Chem., 00, 00 (2013).
INTRODUCTION
substitution patterns [3]. The network of hydrogen bonds in
water influences the reactivity of the substrates, which makes
it an ideal solvent [4]. It is also proposed that the reactions
with negative activation volume might be facilitated by water
[5]. MCRs are believed to exhibit negative activation
volumes owing to the condensation of several molecules into
a single reactive intermediate and product [6].
In recent years, 4H-pyrans and its derivatives have
attracted strong interest because of their useful biological
and pharmacological properties, such as anticoagulant,
spasmolytic, anticancer, and antianaphylactin agents [7].
2-Amino-4H-pyrans can be used as photoactive materials
[8]. Furthermore, polyfunctionalized 4H-chromenes and
4H-pyrans also constitute a structural unit of many
natural products [9]. 2-Amino-4H-chromene derivatives
In recent years, the “greening” of chemical processes to
attain environmental benignness [1] and sustainability
has become a major issue in academia and industry. The
search for alternative reaction media to replace volatile,
flammable, and often toxic solvents commonly used in
organic synthesis is an important objective in the develop-
ment of green chemical processes [2]. Developing multicom-
ponent reaction (MCR) protocols in water is an active area of
research in this direction. MCR offers greater possibilities for
molecular diversity per step with a minimum synthetic time
and effort. It constitutes an attractive synthetic strategy in
drug discovery research, as they provide easy and rapid
access to large libraries of organic compounds with diverse
© 2013 HeteroCorporation

J. M. Khurana, B. Nand, and P. Saluja
Vol 000
are often used in cosmetics and pigments and utilized as
potentially biodegradable agrochemicals [10]. 4H-Pyran
derivatives are also potential calcium channel antagonists
[11] that are structurally similar to biologically active
1,4-dihydropyridines.
Inspired by the recent advances based upon DBU, we
examined first the efficiency of DBU as a promoter for
one-pot synthesis of 2-amino-4H-chromenes via three-
component condensation of aldehydes, malononitrile, or
ethyl cyanoacetate and dimedone (1a), and we were
pleased to find that with a substoichiometric amount
of DBU, 4-chlorobenzaldehyde (1.0 equiv), malononitrile
(1.0 equiv), and dimedone (1.0 equiv) underwent
condensation smoothly, affording 90% of 2-amino-4-
(4-chlorophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-
chromene-3-carbonitrile (2a) in 5 min using water as
solvent under reflux.
This preliminary study prompted us to carry out in-depth
investigation on this novel synthetic protocol. So when this
reaction was repeated at room temperature, no desired
product formation was observed because of insolubility
of the starting materials. The reaction remained incomplete
after 2 h at room temperature when a mixture of ethanol/
water (1:1, v/v) was used, giving 76% yield of the desired
product. Heating the reaction mixture at 80ꢀC using
ethanol/water (1:1, v/v) as solvent yielded 86% of the
desired product in 40 min. No product formation was
observed in the absence of DBU, and the use of 10 mol%
of DBU was found to be sufficient for catalyzing this
reaction. Thus, refluxing all the components in the
presence of 10 mol% of DBU in water proved to be the
optimum condition for this reaction (Scheme 1).
The importance of these compounds has led many
workers to synthesize them using methods including
microwave [12] and ultrasonic irradiation [13], by using
halide ions [14], (S)-proline [15], rare earth perfluorooc-
tanoates [16], hexadecyltrimethylammonium bromide [17],
and magnesium oxide [18] as basic catalysts or 1,1,3,3-
tetramethylguanidinium trifluoroacetate [19] as an ionic
liquid in one-pot reactions. Each of the beforementioned
methods has its own merits and demerits. Thus, in view
of the importance of chromenes/pyrans for diverse
therapeutic activity and in continuation to our endeavor
of developing new methodologies aimed at synthesis of
polyfunctionalized heterocyclic moieties [20], we considered
it necessary to develop a general rapid, high yielding,
environmentally benign, and easy synthetic protocol for a
variety of chromene/pyran derivatives.
RESULTS AND DISCUSSION
We report in this article highly efficient one-pot synthesis of
a variety of chromene/pyran derivatives, namely, tetrahydro-
4H-chromenes (2a-s), tetrahydro[b]pyrans (2t-x), pyrano[d]
pyrimidines (3a-i), and 4H-pyrans (4a-i) catalyzed by 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU) in water under re-
flux. DBU was found to be far superior to other tertiary
amines, and its nucleophilic nature as well as its utility in
organic synthesis has also been investigated over the past
decades [21].
Thereafter, a series of reactions were carried out under
identical reaction conditions. A wide range of diversely
substituted aromatic aldehydes underwent this three-
component cyclocondensation reaction with malononitrile
and dimedone to produce 2-amino-4-aryl-7,7-dimethyl-5-
oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile(Table1,
Scheme 1
O
O
O
R
R1
O
O
O
2a-o
NH2
1a
R
O
O
R1
O
CN
R1
DBU
+
R
H
O
NH2
1b
Water/reflux
2p-s
R1 = CN, COOEt
R
O
O
CN
NH2
1c
O
2t-x
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
1,8-Diazabicyclo[5.4.0]undec-7-ene
entries 2a–g). The substituents in the aromatic ring of
aldehydes did not show any effect on the rate of the reaction
and yield of the products. The heteroaryl aldehydes, such as
2-furaldehyde and 2-thiophenealdehyde (Table 1, entries 2h
and 2i), reacted very smoothly to give the corresponding 4H-
chromenes in good yields. These compounds have been
reported to exhibit molluscicidal activity [22]. Aliphatic
aldehydes also underwent this three-component cyclocon-
densation reaction to give corresponding 4H-chromene
derivatives (Table 1, entry 2j).
We then investigated the scope of extending the
condensation strategy by replacing the active methylene
compound, malononitrile, with ethyl cyanoacetate for reaction
with aromatic aldehydes and dimedone. The reaction under-
went successful condensation under similar reaction
conditions to afford a series of ethyl 2-amino-7,7-dimethyl-
5-oxo-4-aryl-5,6,7,8-tetrahydro-4H-chromene-3-carboxylate
derivatives in high yields (Table 1, entries 2k–o).
To further expand the scope of the present method,
the replacement of 5,5-dimethyl-1,3-cyclohexanedione
(dimedone) with 1,3-cyclohexanedione (1b) was examined
under the same reaction conditions. The reactions proceeded
steadily to provide the targeted tetrahydro-4H-chromenes
(Table 1, entries 2p–s) in good yields. Reactions were also
attempted by replacing dimedone with 1,3-cyclopentanedione
(1c). The components underwent successful condensation to
give tetrahydro [b]pyrans (Table 1, entries 2t–x) in nearly
quantitative yields.
Encouraged by these results, we attempted the present
protocol for condensation of aldehydes, malononitrile,
and 1,3-dimethyl barbituric acid. During our exploratory
experiments, we observed that 4-chlorobenzaldehyde
underwent the three-component condensation smoothly
in the presence of 10 mol% of DBU under reflux to
afford 84% of 7-amino-5-(4-chlorophenyl)-1,3-dimethyl-
2,4-dioxo-1,3,4,5-tetrahydro-2H-pyrano[2,3-d] pyrimidine-
6-carbonitrile in 5 min (Table 2, entry 3a). Thereafter, a
series of differently substituted pyrano[2,3-d]pyrimidines
were prepared from different aromatic aldehydes bearing
electron-withdrawing and electron-donating groups using
10mol% of DBU in aqueous medium under reflux in high
yields (Scheme 2, Table 2, entries 3a–i). These results clearly
indicate that reactions can tolerate a wide range of differently
substituted aromatic aldehydes.
Further, to realize the generality and versatility of the
catalyst, this novel protocol was extended for the synthesis
of 6-amino-4H-pyrans (Table 3, entries 4a–i) by one-pot
condensation of aromatic aldehydes (1.0 equiv), malononitrile
(1.0 equiv), and ethyl acetoacetate (1.0 equiv) in aqueous
media under reflux in the presence of 10 mol% of DBU
(Scheme 3). In all cases, the reactions were remarkably clean,
and no chromatographic separation was required.
Table 1
DBU-catalyzed three-component one-pot synthesis of substituted tetrahydro-4H-chromenes and tetrahydro[b]pyrans.
Product
Rfa
R
R1
1,3-Dicarbonyl Time (min) Yield (%) mp (ꢀC)b (observed) mp (ꢀC) (lit. [14,16,24])
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
2p
2q
2r
2s
0.61
0.39
0.28
0.67
0.58
0.61
0.60
0.66
0.68
0.83
0.88
0.85
0.88
0.82
0.82
0.46
0.34
0.43
0.48
0.23
0.47
0.37
0.21
0.58
4-ClC6H4
CN
CN
CN
CN
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
1c
1c
1c
1c
1c
5
5
10
10
10
5
5
5
5
10
5
90
92
88
91
90
90
86
86
85
88
88
90
85
90
90
88
90
87
86
85
75
68
65
60
210–212
178–180
202–204
216–220
200–202
204–206
190–194
220–224
216–218
174–176
148–150
152–154
152–154
178–180
180–182
228–230
232–234
230–232
198–200
200–202
218–220
190–192
218–220
202–204
214–215
180–181
205
4-O2NC6H4
4-HOC6H4
4-CH3C6H4
224–225
202–203
202–203
210–211
225–226
216–218
172–174
154–155
157–158
157–158
182–183
184–185
228–229
235–236
234–235
205–206
198–200
4-CH3OC6H4 CN
4-BrC6H4
4-FC6H4
2-Furanyl
CN
CN
CN
2-Thiophenyl CN
(CH3)2CH
4-ClC6H4
C6H5
4-CH3C6H4
3-O2NC6H4
4-O2NC6H4
4-ClC6H4
4-O2NC6H4
2-Furanyl
CN
COOC2H5
COOC2H5
COOC2H5
COOC2H5
COOC2H5
CN
5
10
10
10
5
5
5
CN
CN
2-Thiophenyl CN
5
2t
3-O2NC6H4
2-O2NC6H4
4-CH3C6H4
4-HOC6H4
4-ClC6H4
CN
CN
CN
CN
CN
10
10
15
15
20
c
2u
2v
2w
2x
–
c
–
c
–
c
–
aTLC solvent system ethyl acetate : petroleum ether (40:60 v/v).
bSolvent of recrystallization, ethanol. The compounds that showed slight variation from reported melting point was further recrystallized from ethanol, but
no improvement in the melting point of these compounds was noticed.
cKnown compounds, but their melting points were not reported.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

J. M. Khurana, B. Nand, and P. Saluja
Vol 000
Table 2
DBU-catalyzed three-component one-pot synthesis of pyrano[d]pyrimidines.
Product
Rfa
R
Time (min)
Yield (%)
mp (ꢀC)b (observed)
mp (ꢀC) (lit. [19,24])
c
c
c
c
c
3a
3b
3c
3d
3e
3f
3g
3h
3i
0.30
0.19
0.29
0.30
0.20
0.32
0.31
0.21
0.30
4-ClC6H4
4-O2NC6H4
4-FC6H4
4-BrC6H4
4-F3CC6H4
C6H5
2-ClC6H4
3-O2NC6H4
3-ClC6H4
5
5
5
5
10
5
5
5
5
84
82
78
76
80
85
88
86
87
206–208
196–198
164–166
206–210
146–150
198–202
218–220
168–170
196–198
–
–
–
–
–
205–207
c
–
c
–
c
–
aTLC solvent system methanol : chloroform (25:75 v/v).
bSolvent of recrystallization, ethanol.
cKnown compounds, but their melting points were not reported.
According to the proposed mechanism, the first step of
this reaction is the formation of Knoevenagel product by
the condensation of an aldehyde with malononitrile [18].
During such base-catalyzed three-component reaction,
formation of many side products like enaminonitrile,
higher adducts, reduced products, and malononitrile self
addition products have been reported [23]. We believe that
higher basicity and stability of DBU_H+ species generated
in these reactions suppress the formation of these side
products, and hence the yield of the products increases.
The a-cyanocinnamonitrile or a-carbethoxycinnamonitrile
formed initially by Knoevenagel condensation in the
presence of DBU undergo subsequent reactions with C–H
acids, for example, dimedone/1,3-cyclohexanedione/1,3-
cyclopentanedione/1,3-dimethyl barbituric acid or ethyl
acetoacetate in the presence of DBU to give the desired
products (Scheme 4). This has been confirmed by indepen-
dent reactions of a-cyano-4 chlorocinnamonitrile and
a-carbethoxy-4-chlorocinnamonitrile with dimedone in
the presence of DBU, which yielded the desired products
in 94% and 92% yields, respectively. The three reactions
in the absence of DBU showed the formation of
a-cyanocinnamonitrile or a-carbethoxycinnamonitriles only.
The reaction media can be reused for further reactions. For
example, after completion of the reaction, the solid product
was collected by filtration (entry 2a). To the filtrate,
Scheme 2
CH3
N
CH3
N
O
O
R
NH2
CN
O
OH
CN
CN
DBU
R
CHO
+
+
N
N
H3C
Water/reflux
H3C
O
3a-i
O
Table 3
DBU-catalyzed three-component one-pot synthesis of 4H-pyrans.
Product
Rfa
R
Time (min)
Yield (%)
mp (ꢀC)b (observed)
mp (ꢀC) (lit. [18,24])
4a
4b
4c
4d
4e
4f
4g
4h
4i
0.83
0.49
0.85
0.88
0.67
0.85
0.52
0.15
0.67
4-ClC6H4
4-O2NC6H4
3-ClC6H4
4-CH3C6H4
C6H5
2-ClC6H4
3-O2NC6H4
4-HOC6H4
4-CH3OC6H4
5
5
5
10
5
5
5
10
5
95
90
92
85
88
90
88
85
85
168–170
176–178
152–154
178–180
194–195
167–169
184–186
175–177
140–142
172–174
180–183
153–156
177–179
195–196
c
–
182–183
c
–
142–144
aTLC solvent system ethyl acetate : petroleum ether (40:60 v/v).
bSolvent of recrystallization, ethanol.
cKnown compounds, but their melting points were not reported.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
1,8-Diazabicyclo[5.4.0]undec-7-ene
Scheme 3
O
Ar
C2H5
CN
O
O
CN
CN
DBU
O
C2H5
+
R
CHO
+
O
Water/reflux
O
NH2
4a-i
Scheme 4
DBU. The reaction mixture was stirred for specified time;
marginal loss of the yield was observed in the first three runs
(90%, 91%, and 84%), whereas in the fourth and fifth runs,
the yield dropped to 74% and 63%, respectively.
H
N
O
CN
R1
R
H
N
CN
R1
CONCLUSION
N
N
HN
NC
H
R1
O
H
R
DBU is an effective catalyst and provides a new and
useful method to synthesize pyran annulated heterocyclic
systems by condensation of aldehydes, activated C–H acid
compounds, and active methylene compounds. The
procedure offers several advantages including high yields,
operational simplicity, clean reaction conditions, and
minimum pollution of the environment, which make it a
valid contribution to the existing processes in the field of
pyran derivative synthesis.
N
NC
H
OH
H
R1
R
EXPERIMENTAL
H2O
H
CN
R1
All of the chemicals used were purchased from Sigma-
Aldrich, (Bangalore, India) and used as received. Structures of
all of the compounds were identified by their melting point and
spectral data. Thin layer chromatography was used to monitor
reaction progress. Compounds were purified by crystallization
through hot ethanol. Melting points were determined on a
Tropical Labequip apparatus and are uncorrected. IR (KBr) spec-
tra were recorded on Perkin Elmer (USA) FTIR Spectrum-1710,
and the values are expressed as nmax per centimeter. Mass
spectral data were recorded on a Waters (USA) micromass
LCT Mass Spectrometer. The NMR (1H and 13C) spectra were
recorded on Jeol JNM ECX-400P (Tokyo, Japan) at 400MHz
using TMS as an internal standard. The chemical shift values are
recorded on d scale, and the coupling constants (J) are in hertz.
General procedure for 1,8-diazabicyclo[5.4.0]undec-7-ene
catalyzed multicomponent synthesis. Aldehyde (2.5 mmol),
malononitrile (or ethyl cyanoacetate) (2.5 mmol), and 10 mL
of water were placed in a 50-mL round-bottomed flask
mounted over a magnetic stirrer. DBU (10 mol%, 0.25 mmol)
was added to the mixture, and the contents were stirred. To
this stirred mixture, dimedone (or 1,3-cyclohexanedione or
1,3-cyclopentadione or 1,3-dimethylbarbituric acid or ethyl
acetoacetate) (2.5 mmol) was added. The reaction mixture
was refluxed for an appropriate time as mentioned in
Tables 1, 2, or 3. The progress of the reaction was
monitored by TLC (solvent system ethyl acetate : petroleum
ether 40:60) for disappearance of the aldehyde. After
N
R
N
N
O
NH
O
R
H
R1
O
C
N
O
O
N
N
O
O
R
H
R1
N
N
O
NH
O
R
O
R1
NH2
4-chlorobenzaldehyde, malononitrile, and dimedone were
added in the same molar ratio without additional load of
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

J. M. Khurana, B. Nand, and P. Saluja
Vol 000
completion of the reaction, the reaction mixture was allowed
to cool at room temperature, and water was decanted.
Ethanol (3 mL) was added to the mixture, and it was stirred.
The solid was collected by filtration at pump, washed with
ethanol, and crystallized from hot ethanol to obtain pure
products. The aqueous filtrate containing DBU was used as
such for investigating the recyclability of the catalyst.
Representative analytical data.
Acknowledgments. B.N. and P.S. thank CSIR and UGC New
Delhi, India for the grant of Junior/Senior Research Fellowships.
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2-Amino-4-(4-chlorophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-
tetrahydro-4H-chromene-3-carbonitrile (2a, C18H17ClN2O2).
nmax (KBr) 3380, 3183, 2188, 1675, 1635, 1364, 1216 cmÀ1
;
dH (400 MHz, CDCl3) 1.02 (s, 3H, CH3), 1.11 (s, 3H, CH3),
2.10 (d, J = 16.1 Hz, 1H), 2.23 (d, J = 16.1 Hz, 1H), 2.45 (s, 2H,
CH2), 4.38 (s, 1H, CH), 4.59 (s, br, 2H, NH2), 7.18 (d,
J = 8.08 Hz, 2H, Ar), 7.26 (d, J = 6.04 Hz, 2H, Ar); dC
(400 MHz, CDCl3) 27.43, 28.75, 31.00, 35.22, 41.27, 49.34,
57.85, 114.55, 118.53, 128.74, 128.99, 129.12, 141.20, 156.64,
160.68, 195.92; m/z 328.0669 [M+].
Ethyl-2-amino-4-(4-chlorophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-
tetrahydro-4H-chromene-3-carboxylate (2k, C20H22ClNO4).
nmax (KBr) 3480, 3327, 1688, 1660, 1525, 1206 cmÀ1; dH
(400 MHz, CDCl3) 0.96 (s, 3H, CH3), 1.09 (s, 3H, CH3), 1.17
(t, J = 7.32, 3H, CH3), 2.17 and 2.25 (AB system, J = 16.04 Hz,
2H, CHaCHbC(CH3)2), 2.41 (s, 2H, CH2); 4.02–4.04 (m, 2H,
OCH2), 4.46 (s, 1H, CH), 6.20 (s, br, 2H, NH2), 7.15–7.20
(m, 4H, Ar); dC (400 MHz, CDCl3) 14.18, 27.31, 29.09, 32.21,
33.39, 40.58, 50.62, 59.74, 81.04, 116.33, 127.86, 129.62, 131.6,
144.38, 158.26, 161.46, 168.92, 196.40; m/z 375.8429 [M+].
2-Amino-4-(4-nitrophenyl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-
[9] Hatakeyama, S.; Ochi, N.; Numata, H.; Takano, S. Chem
Commun 1988, 1202 (DOI: 10.1039/C39880001202).
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Martin, N.; Martinez, R.; Quinteiro, M.; Seoane, C.; Novoa, H.; Blaton,
N.; Peeters, O. M.; Ranter, C. D. Tetrahedron 2002, 58, 953.
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21, 742.
3-carbonitrile (2q, C16H13N3O4).
nmax (KBr) 3414, 3362, 2196,
1682, 1651, 1518, 1346, 1210 cmÀ1; dH (400 MHz, DMSO-d6)
1.97–1.95 (m, 2H, CH2), 2.26–2.29 (m, 2H, CH2), 2.64 (m,
2H, CH2) 4.35 (s, 1H, CH), 7.19 (s, br, 2H, NH2), 7.46 (d,
J = 8.24 Hz, 2H, Ar) 8.17 (d, J = 7.80 Hz, 2H, Ar); dC
(400 MHz, DMSO-d6) 56.12, 115.24, 120.05, 123.65, 130.87,
146.43, 154.49, 158.21, 165.23, 166.54, 196.76; m/z 311.2716 [M+].
2-Amino-4-(3-nitrophenyl)-5-oxo-4,5,6,7-tetrahydrocyclopenta
[b]pyran-3-carbonitrile (2t, C15H11N3O4).
nmax (KBr) 3369,
[13] Tu, S. J.; Jiang, H.; Zhuang, Q. Y.; Miao, C. B.; Shi, D. Q.;
Wang, X. S.; Gao, Y. Chin. J Org Chem 2003, 23, 488.
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Synlett 2003, 2001; (b) Gao, S.; Tsai, C. H.; Tseng, C..; Yao, C. F. Tetra-
hedron 2008, 64, 9143; (c) Sun, W. B.; Zhang, P.; Fan, J.; Chen, S. H.;
Zhang, Z. H. Synth Commun 2010, 40, 587.
[15] Balalaie, S.; Bararjanian, M.; Amani, A. M.; Movassagh, B.
Synlett 2006, 263.
[16] Wang, L. M.; Shao, J. H.; Tian, H.; Wang, Y. H.; Liu, B. J
Fluorine Chem 2006, 127, 97.
3314, 3187, 2196, 1662, 1348, 1238 cmÀ1; dH (400 MHz,
DMSO-d6) 2.36 (s, 2H, CH2), 2.68–2.80 (m, 2H, CH2), 4.48 (s,
1H, CH), 7.35 (s, br, 2H, NH2), 7.62–7.72 (m, 2H, Ar), 8.05–8.11
(m, 2H, Ar); dC (400 MHz, DMSO-d6) 24.84, 33.49, 35.17, 56.45,
115.92, 119.54, 122.27, 122.38, 130.08, 134.87, 144.85, 147.87,
159.88, 177.01, 201.33; m/z 297.2456 [M+].
7-Amino-1,3-dimethyl-2,4-dioxo-5-(4-trifluoromethylphenyl)-
1,3,4,5-tetrahydro-2H-pyrano [2,3-d]pyrimidine-6-carbonitrile
(3e, C17H13F3N4O3).
nmax (KBr) 3381, 3192, 2199,
[17] Jin, T. S.; Wang, A. Q.; Wang, X.; Zhang, J. S.; Li, T. S.
Synlett 2004, 871.
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Kumar, D.; Reddy, V. B.; Sharad, S.; Dube, U.; Kapur, S. Eur J Med
Chem 2009, 44, 3805.
1708, 1640, 1493, 1224 cmÀ1; dH (400 MHz, DMSO-d6)
3.02 (s, 3H, CH3), 3.31 (s, 3H, CH3), 4.31 (s, 1H, CH),
7.07–7.26 (m, 4H, Ar), 7.30 (s, br, 2H, NH2); dC (400 MHz,
DMSO-d6); 27.77, 39.50, 39.70, 57.79, 85.11, 118.94, 125.29,
126.4, 128.40, 131.01, 148.86, 157.77, 160.13, 160.61; m/z
378.3134 [M+].
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2005, 104, 39.
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Trans 1 2002, 2520; (b) Khurana, J. M.; Kukreja, G. J Heterocycl Chem
2003, 40, 677; (c) Khurana, J. M.; Agarwal, A.; Kukreja, G.
Heterocycles 2006, 68, 1885; (d) Khurana, J. M.; Arora, R.; Satija,
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2010, 66, 5637.
Ethyl-6-amino-5-cyano-2-methyl-4-phenyl-4H-pyran-3-
carboxylate (4e, C16H16N2O3).
nmax (KBr) 3403, 3329,
2190, 1693, 1259, 1060 cmÀ1; dH (400 MHz, CDCl3) 1.08
(t, J = 7.17Hz, 3H, CH3), 2.24 (s, 3H, CH3), 4.00–4.01 (m,
2H, OCH2), 4.41 (s, 1H, CH), 4.49 (s, br, 2H, NH2), 7.24–7.70
(m, 5H, Ar); dC (400 MHz, CDCl3) 13.50, 18.50, 19.51, 38.50,
60.79, 61.60, 107.37, 118.64, 126.51, 128.26, 129.58, 134.30,
134.51, 147.06, 158.41, 166.23, 166.49; m/z 284.3429 [M+].
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
1,8-Diazabicyclo[5.4.0]undec-7-ene
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet