FeCl3-catalyzed three-component reaction: A novel synthesis of tetrahydro-2,6-dioxopyrimidin-4-yl-2,3-dihydrophthalazine-1,4-dione derivatives under solvent-free conditions

Article abstract of DOI:10.1016/j.tet.2014.04.044

Three-component coupling of phthalhydrazide, aldehydes, and barbituric acid has been accomplished in the presence of 15 mol % FeCl₃ under solvent-free conditions to afford the corresponding tetrahydro-2,6- dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-1,4-dione derivatives in excellent yields. This method provides high yields, shorter reaction time, and mild reaction conditions. This is the first example of the condensation of phthalhydrazide, aldehydes, and barbituric acid to provide a novel series of phthalhydrazide derivatives.

Full text of DOI:10.1016/j.tet.2014.04.044

Tetrahedron xxx (2014) 1e8
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
FeCl3-catalyzed three-component reaction: a novel synthesis
of tetrahydro-2,6-dioxopyrimidin-4-yl-2,3-dihydrophthalazine-
1,4-dione derivatives under solvent-free conditions
,
Veeranarayana Reddy Mudumala a, Radha Rani Chinthaparthi b, Tae Jeong Yeon a
*
a Department of Image Science and Engineering, Pukyong National University, Busan 608-737, Republic of Korea
b Department of Chemistry, Sri Venkateswara University, Tirupati 517502, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Three-component coupling of phthalhydrazide, aldehydes, and barbituric acid has been accomplished in
the presence of 15 mol % FeCl3 under solvent-free conditions to afford the corresponding tetrahydro-2,6-
dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-1,4-dione derivatives in excellent yields. This method
provides high yields, shorter reaction time, and mild reaction conditions. This is the first example of the
condensation of phthalhydrazide, aldehydes, and barbituric acid to provide a novel series of phthalhy-
drazide derivatives.
Received 1 March 2014
Received in revised form 10 April 2014
Accepted 14 April 2014
Available online xxx
Keywords:
Ó 2014 Elsevier Ltd. All rights reserved.
Tetrahydro-2,6-dioxopyrimidin-4-yl)-2,3-
dihydrophthalazine-1,4-dione derivatives
FeCl3
Neat condition
Barbituric acid
1. Introduction
Herein multi-component reactions (MCRs) are gaining more
importance in the synthesis of biologically active heterocyclic
Heterocyclic compounds have allured extensive great compre-
hensive due to their therapeutic properties in natural product and
medicinal chemistry.1 Nitrogen-containing heterocycles have wide
range of biologically activities such as antibiotics, fungicides, anti-
HIV protease, plant growth regulators, anti-thrombotic agents,
anti-cancer, anti-inflammatory, anti-allergic, analgesic, glucagon
receptor antagonism, herbicides, and insecticides.2 Phthalazine
derivatives have attracted much attention owing to their biological
activities such as anticonvulsant, cardiotonic, vasorelaxant, phar-
macological properties, and many other applications are well
documented.2,3 Due to their importance, some methods have been
reported for synthesis of phthalazine derivatives.4 Although,
a number of adapted methods under enhanced conditions have
been reported, many of them suffer from one or more drawbacks,
such as unsatisfactory yields, high temperature, long reaction
times, and the use of toxic organic solvents and catalysts. Thus, it is
essential to further develop an efficient and suitable method to
build this type of heterocyclic compounds.
compounds.5 MCRs offer superior potential for molecular diversity
per step with a minimum of synthetic time and under solvent-free
conditions have concerned more attention from chemists princi-
pally from the viewpoint of green chemistry aspects due to for-
mation of carboneheteroatom bond.6 Therefore, research on the
MCR for the synthesis of heterocyclic compounds under solvent-
free conditions is an interesting challenge.
FeCl3 is a ‘green’ and efficient Lewis acid catalyst is potentially
attractive in current organic synthesis by forming carbonecarbon
and carboneheteroatom bonds.7 In recent years there have
been many reports unraveling the utility of FeCl3 in a wide variety
of organic transformations.8 Moreover, FeCl3 is inexpensive, easy
to handle, and are environmentally friendly. However, there
have been no previous reports on the direct synthesis of tetrahy-
dro-2,6-dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-1,4-dione
derivatives (4aet) using FeCl3 as a catalyst.
As part of our continuing effort for accessing heterocyclic
compounds, the development of an efficient green methodologies
and Lewis acid-catalyzed organic transformations,9 herein, we re-
port a new and simple synthesis of tetrahydro-2,6-dioxopyrimidin-
4-yl)-2,3-dihydrophthalazine-1,4-dione derivatives (4aet) pro-
moted by FeCl3 via condensation of phthalhydrazide, aldehydes,
and barbituric acid under neat condition at 60 ꢀC (Scheme 1).
* Corresponding author. Tel.: þ82 51 629 6411; fax: þ82 51 629 6408; e-mail
address: ytjeong@pknu.ac.kr (T. Jeong Yeon).
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.04.044
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V. Reddy Mudumala et al. / Tetrahedron xxx (2014) 1e8
Table 1
R
Influence of the solvent on the synthesis of (4a)a
O
O
O
O
O
FeCl3
HN
NH
NH
NH
NH
N
NH
+ R CHO
(2a-t)
+
N
Solvent-Free
O
O
O
60 °C
O
(1)
(4a-t)
(3)
Scheme 1. Synthesis of tetrahydro-2,6-dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-
1,4-dione derivatives (4aet) catalyzed by FeCl3 under solvent-free condition.
2. Results and discussion
At beginning we performed three-component condensation
reaction of phthalhydrazide (1), 4-ethoxybenzaldehyde (2a), and
barbituric acid (3) in the presence of FeCl3 (15 mol %) at 60 ꢀC.
Curiously, the product 2-((5Z)-5-(4-ethoxybenzylidene)-1,2,5,6-
tetrahydro-2,6-dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-1,4-
dione (4a) was found in 94% yield instead of the cyclization product,
5-(4-ethoxyphenyl)-1H-pyrimido[40,50:3,4]pyrazolo[1,2-b]phthala-
zine-2,4,7,12(3H,5H)-tetraone (5a) (Scheme 2)which was con-
firmed by NMR and HRMS. Probably lower selectivity of FeCl3 and
extended conjugation of the double bonds are the reasons for the
inability of the formation of 5a.
Entry
Solvent (5 mL)
Time (min)
Yieldb (%)
1
2
3
4
5
Toluene
80
180
130
60
55
40
35
75
94
Acetonitrile
Tetrahydrofuran
Ethanol
Neat
15
a
Reaction of phthalhydrazide(1 mmol), 4-ethoxybenzaldehyde (1 mmol), and
barbituric acid (1 mmol) catalyzed by 15 mol % of FeCl3 at 60 ꢀC.
b
Isolated yield.
Table 2
Influence of the catalyst on the synthesis of (4a)a
Entry
Catalyst
Catalyst (mol %)
Time (min)
Yieldb (%)
1
2
3
4
5
6
7
8
Free
ZnCl2
FeF3
InF3
d
15
15
15
15
15
15
15
5
110
60
45
40
70
100
55
15
40
15
15
30
40
60
70
55
40
40
94
50
75
94
GaCl3
Y(OAc)3$H2O
Cd(ClO4)2$H2O
FeCl3
FeCl3
FeCl3
Scheme 2. Condensation of phthalhydrazide (1 mmol), 4-ethoxybenzaldehyde
(1 mmol), and barbituric acid (1 mmol).
9
10
11
10
30
FeCl3
Encouraged by this result, we chosen this reaction as a model
reaction to study the reaction conditions further for the synthesis of
tetrahydro-2,6-dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-1,4-
dione derivatives (4aet). At first investigated the effect of solvent
on model reaction in the presence of FeCl3 catalyst at 60 ꢀC. The
results are summarized in Table 1. It was observed that, among all
solvents ethanol shown good product yield (Table 1, entry 4), but
even better result was obtained under solvent-free condition and
gave excellent product yield in less reaction time and high purity of
product (Table 1, entry 5).
The catalyst plays an important role in the success of the re-
action in terms of rate of the reaction and yields. After determined
the optimized solvent conditions, we performed the scope of the
catalyst. To find the best catalyst, we screened the model reaction in
the presence and absence of different Lewis acid catalysts. In all
cases the catalysts were taken as 15 mol % and reaction was done
under solvent-free conditions at 60 ꢀC (Table 2). In absence of the
catalyst, the model reaction could be carried out but the product
was obtained in very low yield after prolonged reaction time (Table
2, entry 1). But in the presence of the catalysts showed good results
and in them found that, FeCl3 proved to be the most efficient cat-
alyst for the model reaction (Table 2, entry 8).
a
Reaction of phthalhydrazide(1 mmol), 4-ethoxybenzaldehyde (1 mmol), and
barbituric acid (1 mmol) under solvent-free conditions at 60 ꢀC.
b
Isolated yield.
zine-1,4-dione derivatives (4aet) via this novel green chemical
approach, quantity of the catalyst required was determined. Ini-
tially, 5 mol % FeCl3was used to perform the reaction. But it requires
slightly long reaction time. Therefore, the loading of the catalyst was
gradually increased from 5 mol % to 30 mol % (Table 2, entries 8e11).
It was found that 15 mol % of FeCl3 is optimal to carry out the re-
actions in a short duration (Table 2, entry 8). The use of excess of
catalyst did not alter either reaction time or yield of the product.
Thus, the use of 15 mol % FeCl3 at 60 ꢀC is ideal to achieve the desired
product in good yields.
We also investigated different temperatures for the model re-
action (Table 3). It was observed that fast reaction occurred on
raising the temperature from 30 ꢀC to reflux and the yield of pre-
ferred product increased significantly. We were satisfied to find
that the reaction proceeded smoothly and almost complete con-
version of reactants was observed at 60 ꢀC to afford the desired
product (4a) in 94% yield within 15 min (Table 3, entry 3). Further
increase in the temperature did not affect the product yield.
Having optimized reaction conditions for the synthesis of tetra-
hydro-2,6-dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-1,4-dione
In order to optimize the suitable reaction conditions for prepa-
ration of tetrahydro-2,6-dioxopyrimidin-4-yl)-2,3-dihydrophthala-
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V. Reddy Mudumala et al. / Tetrahedron xxx (2014) 1e8
Table 4 (continued )
3
Table 3
Effect of temperature for the synthesis of (4a)a
Entry
Aldehydes (R)
Product
Time Yieldb Mp (ꢀC)
(min) (%)
OEt
O
O
O
O
CHO
HN
NH
NH
NH
NH
N
FeCl3
Neat
+
+
N
5
21
90
274e276
NH
O
O
O
O
O
OEt
(2a)
(1)
(3)
(4a)
Entry
Temp (ꢀC)
Time (min)
Yieldb (%)
1
2
3
4
5
30
40
60
100
Reflux
150
80
15
15
10
40
94
94
94
15
6
16
93
258e260
a
Reaction of phthalhydrazide(1 mmol), 4-ethoxybenzaldehyde (1 mmol), and
barbituric acid (1 mmol) catalyzed by FeCl3 under solvent-free conditions.
b
Isolated yield.
derivatives (4aet) using 15 mol % FeCl3 as the catalyst under solvent-
free conditions at 60 ꢀC we subsequently applied for a variety of
aldehydes including ortho-, meta-, and para-substituted arylalde-
hydes (Table 4). Notably, sterically hindered ortho-substituted
7
18
91
290e292
Table 4
FeCl3-catalyzed multi-component synthesis of tetrahydro-2,6-dioxopyrimidin-4-
yl)-2,3-dihydrophthalazine-1,4-dione derivativesa
Entry
Aldehydes (R)
Product
Time Yieldb Mp (ꢀC)
(min) (%)
8
20
94
248e250
1
15
94
268e270
9
16
92
330e332
2
16
93
255e257
10
19
90
248e250
3
20
90
270e272
11
17
91
232e234
4
18
91
262e264
(continued on next page)
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4
V. Reddy Mudumala et al. / Tetrahedron xxx (2014) 1e8
Table 4 (continued)
Table 4 (continued )
Entry
Aldehydes (R)
Product
Time Yieldb Mp (ꢀC)
(min) (%)
Entry
Aldehydes (R)
Product
Time Yieldb Mp (ꢀC)
(min) (%)
19
20
22
20
90
90
272e274
280e282
12
22
90
258e260
13
25
89
280e282
a
Reaction of aldehydes (1 mmol), phthalhydrazide(1 mmol), and barbituric acid
(1 mmol) catalyzed by FeCl3 under solvent-free microwave irradiation at 60 ꢀC.
b
Isolated yield.
aldehydes (Table 4, entries 14e16) also participated effectively in
this reaction. Both the electron rich (Table 4, entries 1e4, 6, 8, 9 and
17e20) as well as electron deficient substrates (Table 4, entries 5 and
7) are found to be equally effective for this conversion. The acid-
sensitive heterocyclic aldehyde, thiophene-2-carbaldehyde was
also obtained in good yield (Table 4, entry 19). But the meta-
substituted aldehydes resulted little bit lesser product yields (Table
4, entries 10e13). All of the new structures were characterized by 1H
NMR, 13C NMR, and HRMS.
14
21
90
276e278
2.1. Spectral analysis of (Z)-2-(5-(2-methylbenzylidene)-2,6-
dioxo-1,2,5,6-tetrahydropyrimidin-4-yl)-2,3-
dihydrophthalazine-1,4-dione (4p)
15
17
91
238e240
Compound 4p showed absorption bands in IR spectrum (Fig. 1)
at 3070 and 1922 cmꢁ1 indicating that the presence of unsatura-
tion, which is as internal double bond and it clearly observed as Z-
configuration at C]C due to appearance of a strong absorption
band at 746 cmꢁ1. The carbonyl groups of this compound showed
an absorption band at 1691 cmꢁ1 indicating that the C]O is in an
amide function.
16
19
90
256e258
17
20
91
230e232
18
18
94
268e270
Fig. 1. FTIR spectrum of compound 4p.
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V. Reddy Mudumala et al. / Tetrahedron xxx (2014) 1e8
5
In PMR spectrum (Fig. 2) of this compound the basic protons
(NeH), olefinic proton (C]CeH), and methyl protons appear as
singlet at 11.40, 11.17, 8.40, and 2.27 ppm, respectively. All the
aromatic protons appear in the region of 8.08e7.15 ppm. All these
d
d
protons are correlating to each other in their corresponding cor-
relation spectroscopy (COSY) (Fig. 3). At the inset of the COSY
spectrum shows a part of nuclear Overhauser exchange spectros-
copy (NOESY) spectrum indicating that a much weaker correlation
through-space appears between NeH and C]CeH protons at
8.40 ppm. It indicates that the compound exists in Z-configuration
at the double bond.
Fig. 4. 1D-CMR spectrum of compound 4p.
Fig. 2. 1D-PMR spectrum of compound 4p.
Fig. 5. HSQC spectrum of compound 4p.
conjugated C]O bond of 6b. Finally, the products (4aet) obtained
by elimination of water molecule in good yields rather than the
cyclization products (5aet).
Fig. 3. HeH COSY (inset: part of NOESY of NeH & C]CeH) spectrum of compound 4p.
Scheme 3. Schematic presentation of the possible mechanism for products 4aet
formation.
The CMR spectrum (Fig. 4) shows that the amide carbonyl car-
bons and the olefinic carbon appear at high frequency region. And
also the aromatic carbons appear at lower field region. The olefinic
carbon and its corresponding protons are in correlation in their
heteronuclear single quantum correlation (HSQC) spectrum (Fig. 5).
And all the remaining protons are also correlating with corre-
sponding carbons in their single quantum correlation spectrum.
The carbons, which have no protons are not correlating with any
other proton nuclei.
The role of FeCl3 as catalyst in titled compounds (4aet) syn-
thesis should be postulated as shown in Scheme 3. The multi-
component reaction should be proceeding in a stepwise manner.
At first, the reaction occurs via Knoevenagel condensation between
enolic form of barbituric acid (3) and aldehyde (2) in the presence
of FeCl3 catalyst to form the intermediate, 6a. This is enolising as 6b
to stabilize by extending conjugation in presence of catalyst. After
that it transforms immediately into one more intermediate, 7, by
Michael addition of 2,3-dihydrophthalazine-1,4-dione (1) at
3. Conclusion
In summary, we have successfully developed a green and facile
method for the synthesis of tetrahydro-2,6-dioxopyrimidin-4-yl)-
2,3-dihydrophthalazine-1,4-dione derivatives from easily available
starting materials using FeCl3 as a catalyst under solvent-free
conditions. The mild reaction conditions, simple work-up without
column chromatographic purification, neat condition, operational
simplicity, and high yields are the advantages of this protocol.
4. Experimental
4.1. General
Chemicals were purchased from Aldrich and Alfaaesar Chemical
Companies. NMR spectra were recorded in parts per million (ppm)
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6
V. Reddy Mudumala et al. / Tetrahedron xxx (2014) 1e8
in DMSO-d6 on a Jeol JNM ECP 400 NMR instrument using TMS as
internal standard. Mass spectra were recorded on a Jeol JMS-700
mass spectrometer. All melting points were determined using
open capillaries on an Electrothermal-9100 (Japan) instrument.
HRMS (ESI, m/z): calcd for C19H11N5O6 (MþHþ) 405.0709, found:
405.0704.
4.2.6. 2-((13Z)-5-(4-Methylbenzylidene)-1,2,5,6-tetrahydro-2,6-
dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-1,4-dione (4f). Yield
4.2. Synthesis of 2-((13Z)-5-(4-ethoxybenzylidene)-1,2,5,6-
tetrahydro-2,6-dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-
1,4-dione (4a)
93%; yellow solid; mp 258e260 ꢀC. IR (KBr):
n
¼3290, 3096, 2840,
1749, 1665, 1621, 1581, 712 cmꢁ1
.
1H NMR (400 MHz, DMSO-d6):
d
11.38 (s, 1H), 11.23 (s, 1H), 8.23 (s, 1H), 8.08e8.05 (m, 4H),
7.88e7.85 (m, 2H), 7.26 (d, J¼8.0 Hz, 2H), 2.34 (s, 3H); 13C NMR
A
mixture of phthalhydrazide (1, 1 mmol), 4-ethoxtben-
(100 MHz, DMSO-d6) d 163.6, 161.8, 155.0, 150.2, 143.5, 134.0, 132.6,
zaldehyde (2a, 1 mmol), barbituric acid (3, 1 mmol), and FeCl3
(15 mol %) was stirred at 60 ꢀC under solvent-free condition for
15 min (Table 4, entry 1). The progress of the reaction was moni-
tored by TLC. After completion of reaction, the reaction mixture was
washed with water and ethanol and residue recrystallized from
ethanol to afford the pure product 4a (94%).
129.9, 128.8, 127.2, 125.1, 117.8, 21.4; HRMS (ESI, m/z): calcd for
C
20H14N4O4 (MþHþ) 374.1015, found: 374.1015.
4.2.7. 2-((13Z)-5-(4-Fluorobenzylidene)-1,2,5,6-tetrahydro-2,6-
dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-1,4-dione (4g). Yield
92%; yellow solid; mp 290e292 ꢀC. IR (KBr):
n
¼3390, 3096, 2851,
1761, 1679, 1659, 1588, 695 cmꢁ1
.
1H NMR (400 MHz, DMSO-d6):
4.2.1. 2-((13Z)-5-(4-Ethoxybenzylidene)-1,2,5,6-tetrahydro-2,6-
d 11.41 (s,1H),11.27 (s,1H), 8.26 (s,1H), 8.23e8.20 (m, 2H), 8.07e8.05
dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-1,4-dione (4a). Yield
(m, 2H), 7.87e7.85 (m, 2H), 7.28 (t, J¼8.8 Hz, 2H); 13C NMR (100 MHz,
94%; yellow solid; mp 268e270 ꢀC. IR (KBr):
n
¼3350, 3196, 2853,
DMSO-d6)
d
164.2 (CeF, d, J¼252.2 Hz), 163.4, 161.8, 153.5, 150.2,
1740, 1695, 1664, 1591, 708 cmꢁ1
.
1H NMR (400 MHz, DMSO-d6):
136.4, 136.3, 132.6, 129.2, 127.2, 125.1, 118.7, 115.3, 115.1; HRMS (ESI,
d
11.29 (s, 1H), 11.17 (s, 1H), 8.35 (d, J¼8.8 Hz, 2H), 8.24 (s, 1H),
m/z): calcd for C19H11FN4O4 (MþHþ) 378.0764, found: 378.0760.
8.07e8.05 (m, 2H), 7.88e7.86 (m, 2H), 7.02 (d, J¼9.1 Hz, 2H),
4.15e4.11 (q, 2H), 1.34 (t, J¼6.9 Hz, 3H); 13C NMR (100 MHz, DMSO-
4.2.8. 2-((13Z)-5-(4-Isopropylbenzylidene)-1,2,5,6-tetrahydro-2,6-
d6)
d
164.0, 162.8, 162.2, 155.1, 150.2, 137.6, 132.6, 127.2, 125.1, 125.0,
dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-1,4-dione (4h). Yield
115.3, 114.3, 63.7, 14.4; HRMS (ESI, m/z): calcd for C21H16N4O5
90%; yellow solid; mp 248e250 ꢀC. IR (KBr):
n
¼3351, 3086, 2853,
1H NMR (400 MHz, DMSO-d6):
11.37 (s, 1H), 11.22 (s, 1H), 8.25 (s, 1H), 8.07e8.05 (m, 3H),
(MþHþ) 404.1121, found: 404.1120.
1740, 1693, 1660, 1581, 712 cmꢁ1
.
d
4.2.2. 2-((13Z)-5-(4-Methoxybenzylidene)-1,2,5,6-tetrahydro-2,6-
dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-1,4-dione (4b). Yield
7.88e7.86 (m, 3H), 7.34 (d, J¼8.4 Hz, 2H), 2.95e2.90 (m, 1H), 1.20 (d,
J¼6.9 Hz, 6H); 13C NMR (100 MHz, DMSO-d6)
d 163.6, 161.8, 154.9,
93%; yellow solid; mp 255e257 ꢀC. IR (KBr):
n
¼3370, 3042, 2847,
1H NMR (400 MHz, DMSO-d6):
11.31 (s, 1H), 11.18 (s, 1H), 8.36 (d, J¼9.1 Hz, 2H), 8.24 (s, 1H),
8.07e8.05 (m, 2H), 7.88e7.86 (m, 2H), 7.04 (d, J¼8.8 Hz, 2H), 3.86 (s,
3H); 13C NMR (100 MHz, DMSO-d6)
163.9, 163.4, 162.2, 154.9,
153.8, 150.2, 134.1, 132.6, 130.2, 128.1, 127.1, 126.1, 125.5, 125.1, 117.9,
1745, 1693, 1646, 1545, 710 cmꢁ1
.
33.6, 23.4; HRMS (ESI, m/z): calcd for
402.1328, found: 402.1325.
C
22H18N4O4 (MþHþ)
d
d
4.2.9. 2-((13Z)-5-(4-Hydroxybenzylidene)-1,2,5,6-tetrahydro-2,6-
150.2, 137.5, 132.6, 128.0, 127.1, 125.1, 115.5, 113.9, 55.6; HRMS (ESI,
dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-1,4-dione (4i). Yield
m/z): calcd for C20H14N4O5 (MþHþ) 390.0964, found: 390.0960.
92%; yellow solid; mp 330e332 ꢀC. IR (KBr):
n
¼3350, 3100, 2858,
1H NMR (400 MHz, DMSO-d6):
11.27 (s, 1H), 11.14 (s, 1H), 10.82 (s, 1H), 8.32 (d, J¼7.6 Hz, 2H), 8.21
(s, 1H), 8.08e8.05 (m, 2H), 7.87 (t, J¼5.8 Hz, 2H), 6.87 (d, J¼8.8 Hz,
2H); 13C NMR (100 MHz, DMSO-d6)
164.1, 163.0, 162.3, 155.5,
1748, 1695, 1664, 1590, 710 cmꢁ1
d
.
4.2.3. 2-((13Z)-5-(4-Bromobenzylidene)-1,2,5,6-tetrahydro-2,6-
dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-1,4-dione (4c). Yield
90%; yellow solid; mp 270e272 ꢀC. IR (KBr):
n
¼3203, 3092, 2850,
d
1726, 1660, 1654, 1598, 711 cmꢁ1
.
1H NMR (400 MHz, DMSO-d6):
150.3, 138.3, 132.6, 127.2, 125.2, 123.8, 115.5, 114.2; HRMS (ESI, m/z):
calcd for C19H12N4O5 (MþHþ) 376.0808, found: 376.0810.
d
11.42 (s, 1H), 11.28 (s, 1H), 8.21 (s, 1H), 8.07e8.04 (m, 2H), 7.97 (d,
J¼8.8 Hz, 2H), 7.86 (dd, J¼2.1, 10.2 Hz, 2H), 7.66e7.62 (m, 2H); 13C
NMR (100 MHz, DMSO-d6)
d
163.2, 161.6, 153.1, 150.2, 134.7, 132.6,
4.2.10. 2-((13Z)-5-(3-Bromobenzylidene)-1,2,5,6-tetrahydro-2,6-
131.9, 131.0, 128.1, 127.1, 125.8, 125.5, 125.1, 119.7; HRMS (ESI, m/z):
dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-1,4-dione (4j). Yield
calcd for C19H11BrN4O4 (MþHþ) 439.219, found: 439.215.
89%; yellow solid; mp 248e250 ꢀC. IR (KBr):
n
¼3290, 3096, 2863,
1H NMR (400 MHz, DMSO-d6):
11.46 (s, 1H), 11.30 (s, 1H), 8.27 (s, 1H), 8.21 (s, 1H), 8.08e8.05 (m,
2H), 7.88e7.85 (m, 3H), 7.66 (d, J¼7.6 Hz, 1H), 7.39 (t, J¼7.6 Hz, 1H);
13C NMR (100 MHz, DMSO-d6)
163.1, 161.5, 152.5, 150.2, 135.1,
1760, 1685, 1654, 1586, 715 cmꢁ1
d
.
4.2.4. 2-((13Z)-5-(4-Chlorobenzylidene)-1,2,5,6-tetrahydro-2,6-
dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-1,4-dione (4d). Yield
91%; yellow solid; mp 262e264 ꢀC. IR (KBr):
n
¼3309, 3012, 2850,
d
1761, 1662, 1644, 1559, 718 cmꢁ1
.
1H NMR (400 MHz, DMSO-d6):
134.3, 134.1, 132.6, 131.7, 130.0, 127.2, 125.2, 121.0, 120.6; HRMS (ESI,
d
11.42 (s, 1H), 11.21 (s, 1H), 8.24 (s, 1H), 8.07 (d, J¼8.8 Hz, 3H),
m/z): calcd for C19H11BrN4O4 (MþHþ) 439.219, found: 439.214.
7.89e7.85 (m, 2H), 7.51 (d, J¼8.4 Hz, 3H); 13C NMR (100 MHz,
DMSO-d6)
d
163.2, 161.5, 153.0, 150.1, 136.7, 134.7, 132.5, 131.5, 128.0,
4.2.11. 2-((13Z)-5-(3-Methylbenzylidene)-1,2,5,6-tetrahydro-2,6-
127.1, 125.1, 119.6; HRMS (ESI, m/z): calcd for C19H11ClN4O4 (MþHþ)
dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-1,4-dione (4k). Yield
394.768, found: 394.764.
92%; yellow solid; mp 232e234 ꢀC. IR (KBr):
n
¼3352, 3086, 2857,
1751, 1678, 1639, 1588, 709 cmꢁ1
.
1H NMR (400 MHz, DMSO-d6):
4.2.5. 2-((13Z)-5-(4-Nitrobenzylidene)-1,2,5,6-tetrahydro-2,6-
d 11.40 (s, 1H), 11.24 (s, 1H), 8.23 (s, 1H), 8.08e8.05 (m, 3H),
dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-1,4-dione (4e). Yield
7.88e7.85 (m, 3H), 7.33 (d, J¼7.2 Hz, 2H), 2.31 (s, 3H); 13C NMR
90%; yellow solid; mp 274e276 ꢀC. IR (KBr):
n
¼3350, 3017, 2853,
(100 MHz, DMSO-d6) d 163.4, 161.6, 154.9, 150.3, 137.2, 133.6, 133.0,
1740, 1657, 1634, 1596, 717 cmꢁ1
.
1H NMR (400 MHz, DMSO-d6):
132.6, 130.3, 128.0, 127.1, 125.1, 118.9, 20.9; HRMS (ESI, m/z): calcd
d
11.52 (s, 1H), 11.34 (s, 1H), 8.31 (s, 1H), 8.27e8.20 (m, 2H),
for C20H14N4O4 (MþHþ) 374.1015, found: 374.1010.
8.07e8.04 (m, 2H), 8.00 (d, J¼7.2 Hz, 2H), 7.87e7.83 (m, 2H); 13C
NMR (100 MHz, DMSO-d6)
d
162.7, 161.5, 151.2, 150.3, 148.0, 140.0,
4.2.12. 2-((13Z)-5-(3-Fluorobenzylidene)-1,2,5,6-tetrahydro-2,6-
132.6, 132.3, 127.2, 125.2, 122.7, 122.3; HRMS (ESI, m/z): calcd for
dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-1,4-dione (4l). Yield
Please cite this article in press as: Reddy Mudumala, V.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.04.044

V. Reddy Mudumala et al. / Tetrahedron xxx (2014) 1e8
7
90%; yellow solid; mp 258e260 ꢀC. IR (KBr):
1749, 1690, 1650, 1598, 705 cmꢁ1 1H NMR (400 MHz, DMSO-d6):
11.46 (s, 1H), 11.31 (s, 1H), 8.24 (s, 1H), 8.08e8.05 (m, 2H),
n
¼3299, 3076, 2850,
DMSO-d6):
2H), 7.89e7.86 (m, 2H), 7.83 (s, 2H), 3.81 (s, 6H), 3.78 (s, 3H); 13C
NMR (100 MHz, DMSO-d6) 163.7, 162.1, 155.2, 151.9, 150.1, 141.9,
d 11.37 (s, 1H), 11.24 (s, 1H), 8.25 (s, 1H), 8.07e8.05 (m,
.
d
d
8.02e7.99 (m, 1H), 7.88e7.85 (m, 2H), 7.75 (d, J¼7.7 Hz, 1H),
132.5, 127.5, 125.1, 117.2, 112.6, 60.3, 56.0; HRMS (ESI, m/z): calcd for
C
7.51e7.46 (m,1H), 7.37e7.33 (m,1H); 13C NMR (100 MHz, DMSO-d6)
22H18N4O7 (MþHþ) 450.1175, found: 450.1172.
d
163.1, 161.5, 160.3 (CeF, d, J¼240.0 Hz), 152.7, 150.2, 134.9, 132.6,
130.0,129.9,129.4,127.2,125.1, 120.4,118.8e118.4; HRMS (ESI, m/z):
calcd for C19H11FN4O4 (MþHþ) 378.0764, found: 378.0758.
4.2.19. 2,3-Dihydro-2-((13Z)-1,2,5,6-tetrahydro-2,6-dioxo-5-((thio-
phen-2-yl)methylene)pyrimidin-4-yl)phthalazine-1,4-dione
(4s). Yield 88%; yellow solid; mp 272e274 ꢀC. IR (KBr):
n
¼3390,
3022, 2852, 1751, 1679, 1659, 1597, 700 cmꢁ1. 1H NMR (400 MHz,
DMSO-d6): 11.32 (s, 1H), 11.28 (s, 1H), 8.56 (s, 1H), 8.27e8.25 (m,
1H), 8.16e8.15 (m, 1H), 8.08e8.05 (m, 2H), 7.88e7.7.85 (m, 2H),
7.33e7.32 (m, 1H); 13C NMR (100 MHz, DMSO-d6)
163.5, 163.0,
4.2.13. 2-((13Z)-5-(3-Nitrobenzylidene)-1,2,5,6-tetrahydro-2,6-
dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-1,4-dione (4m). Yield
d
89%; yellow solid; mp 280e282 ꢀC. IR (KBr):
n
¼3300, 3056, 2831,
1H NMR (400 MHz, DMSO-d6):
11.50 (s, 1H), 11.35 (s, 1H), 8.90 (s, 1H), 8.31e8.29 (m, 1H), 8.21 (d,
1726, 1670, 1689, 1598, 715 cmꢁ1
.
d
d
150.0,145.8,145.7,142.1,136.6,132.6,128.4,127.1,125.1,111.6; HRMS
J¼7.6 Hz, 1H), 8.07e8.05 (m, 2H), 7.89e7.85 (m, 3H), 7.72
(ESI, m/z): calcd for
366.0420.
C
17H10N4O4S (MþHþ) 366.0423, found:
(t, J¼8.0 Hz, 1H); 13C NMR (100 MHz, DMSO-d6)
d
162.8, 161.5, 151.2,
150.3, 147.1, 138.4, 134.5, 132.6, 129.4, 126.1, 125.5, 125.1, 121.6;
HRMS (ESI, m/z): calcd for C19H11N5O6 (MþHþ) 405.0709, found:
405.0702.
4.2.20. 2-((5Z)-5-((Benzo[d][1,3]dioxol-5-yl)methylene)-1,2,5,6-
tetrahydro-2,6-dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-1,4-di-
one (4t). Yield 90%; yellow solid; mp 280e282 ꢀC. IR (KBr):
n
¼3370,
3016, 2841, 1755, 1679, 1648, 1593, 698 cmꢁ1. 1H NMR (400 MHz,
DMSO-d6):
4.2.14. 2-((13Z)-5-(2-Fluorobenzylidene)-1,2,5,6-tetrahydro-2,6-
dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-1,4-dione (4n). Yield
d
11.33 (s, 1H), 11.21 (s, 1H), 8.25 (d, J¼7.0 Hz, 1H), 8.19 (s,
90%; yellow solid; mp 276e278 ꢀC. IR (KBr):
n
¼3310, 3096, 2851,
1H NMR (400 MHz, DMSO-d6):
11.47 (s, 1H), 11.29 (s, 1H), 8.27 (s, 1H), 8.08e8.05 (m, 2H),
7.94e7.86 (m, 3H), 7.55e7.51 (m, 1H), 7.30e7.22 (m, 2H); 13C NMR
(100 MHz, DMSO-d6)
1H), 8.07e8.05 (m, 2H), 7.88e7.86 (m, 2H), 7.72 (dd, J¼2.2, 8.8 Hz,
1741, 1670, 1650, 1594, 713 cmꢁ1
.
1H), 7.06 (d, J¼8.3 Hz, 1H), 6.17 (s, 2H); 13C NMR (100 MHz, DMSO-
d
d6) d 163.8, 162.2, 154.9, 151.9, 150.1, 147.3, 133.7, 132.6, 126.7, 125.1,
115.9, 112.4, 108.2, 102.3; HRMS (ESI, m/z): calcd for C20H12N4O6
d
162.7, 161.8, 160.5 (CeF, d, J¼200.0 Hz),
(MþHþ) 404.0757, found: 404.0755.
150.2,145.5,133.5,132.6,132.2,125.1,123.8,121.6,121.5,121.3,115.3,
115.1; HRMS (ESI, m/z): calcd for C19H11FN4O4 (MþHþ) 378.0764,
found: 378.0761.
Supplementary data
NMR spectra of all compounds. Supplementary data associated
with this article can be found in the online version, at http://
dx.doi.org/10.1016/j.tet.2014.04.044.
4.2.15. 2-((13Z)-5-(2-Bromobenzylidene)-1,2,5,6-tetrahydro-2,6-
dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-1,4-dione (4o). Yield
91%; yellow solid; mp 238e240 ꢀC. IR (KBr):
n
¼3290, 3088, 2850,
1H NMR (400 MHz, DMSO-d6):
11.48 (s, 1H), 11.25 (s, 1H), 8.22 (s, 1H), 8.08e8.06 (m, 2H),
7.89e7.86 (m, 2H), 7.70 (dd, J¼2.2, 9.1 Hz, 2H), 7.39e7.36 (m, 2H);
13C NMR (100 MHz, DMSO-d6)
162.6, 160.8, 151.8, 150.2, 134.2,
1761, 1666, 1633, 1580, 712 cmꢁ1
.
References and notes
d
1. (a) Gribble, G. W. J. Chem. Soc., Perkin Trans. 1 2000, 1045e1075; (b) Baran, P. S.;
Richter, J. M.; Lin, D. W. Angew. Chem., Int. Ed. 2005, 44, 606e609; (c) Tc¸ rc¸ k, M.;
Abid, M.; Mhadgut, S. C.; Tc¸ rc¸ k, B. Biochemistry 2006, 45, 5377e5383; (d) Eicher,
T.; Hauptmann, S. The Chemistry of Heterocycles; Wiley-VCH: Weinheim, Ger-
many, 2003.
2. (a) Fyaz, I. J. Fluorine Chem. 2002, 118, 27e33; (b) Litvinov, V. P. Russ. Chem. Rev.
2003, 72, 69e85; (c) Kim, J. S.; Rhee, H. K.; Park, H. J.; Lee, S. K.; Lee, C. O.; Park
Choo, H. Y. Bioorg. Med. Chem. 2008, 16, 4545e4550; (d) Zhang, L.; Guan, L. P.;
Sun, X. Y.; Wei, C. X.; Chai, K. Y.; Quan, Z. S. Chem. Biol. Drug Des. 2009, 73,
313e319; (e) Ryu, C. K.; Park, R. E.; Ma, M. Y.; Nho, J. H. Bioorg. Med. Chem. Lett.
2007, 17, 2577e25780; (f) Li, J.; Zhao, Y. F.; Yuan, X. Y.; Xu, J. X.; Gong, P. Molecules
2006, 11, 574e582; (g) Sinkkonen, J.; Ovcharenko, V.; Zelenin, K. N.; Bezhan, I. P.;
Chakchir, B. A.; Al-Assar, F.; Pihlaja, K. Eur. J. Org. Chem. 2002, 2046e2053; (h)
Hoepping, A.; Diekers, M.; Deuther-Conrad, W.; Scheunemann, M.; Fischer, S.;
Hiller, A.; Wegner, F.; Steinbach, J.; Brust, P. Bioorg. Med. Chem. 2008, 16,
1184e1194; (i) Wawer, I.; Pisklak, M.; Chilmonczyk, Z. H. J. Pharm. Biomed. Anal.
2005, 38, 865e870.
d
132.5, 131.9, 127.1, 126.7, 125.1, 123.3, 121.3; HRMS (ESI, m/z): calcd
for C19H11BrN4O4 (MþHþ) 439.219, found: 439.216.
4.2.16. 2-((13Z)-5-(2-Methylbenzylidene)-1,2,5,6-tetrahydro-2,6-
dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-1,4-dione (4p). Yield
90%; yellow solid; mp 256e258 ꢀC. IR (KBr):
n
¼3452, 3314, 3070,
1H NMR (400 MHz,
11.42 (s, 1H), 11.19 (s, 1H), 8.40 (s, 1H), 8.09e8.06 (m,
2959, 2872, 1691, 1615, 1569, 1226, 746 cmꢁ1
DMSO-d6):
.
d
2H), 7.89e7.86 (m, 2H), 7.57 (d, J¼7.6 Hz, 1H), 7.31 (t, J¼7.3 Hz, 1H),
7.24 (d, J¼7.3 Hz, 1H), 7.17 (t, J¼7.6 Hz, 1H), 2.27 (s, 3H); 13C NMR
(100 MHz, DMSO-d6)
d 163.1, 161.1, 153.7, 150.3, 137.6, 133.1, 132.6,
130.4, 129.9, 129.6, 127.2, 125.1, 124.9, 120.4, 19.7; (ESI, m/z): calcd
3. (a) El-Saka, S. S.; Soliman, A. H.; Imam, A. M. Afinidad 2009, 66, 167e172; (b)
Piatnitski, E. L.; Duncton, M. A. J.; Kiselyov, A. S.; Katoch-Rouse, R.; Sherman, D.;
Milligan, D. L.; Balagtas, C.; Wong, W. C.; Kawakami, J.; Doody, J. F. Bioorg. Med.
Chem. Lett. 2005, 15, 4696e4698; (c) Duncton, M. A. J.; Piatnitski, E. L.; Katoch, R.
R.; Smith, L. M.; Kiselyov, A. S.; Milligan, D. L.; Balagtas, C.; Wong, W. C.; Ka-
wakami, J.; Doody, J. F. Bioorg. Med. Chem. Lett. 2006, 16, 1579e1581; (d) Wu, H.;
Chen, X. M.; Wan, Y.; Xin, H. Q.; Xu, H. H.; Ma, R.; Yue, C. H.; Pang, L. L. Lett. Org.
Chem. 2009, 6, 219e223.
4. (a) Liu, L. P.; Lu, J. M.; Shi, M. Org. Lett. 2007, 9, 1303e1306; (b) Amarasekara, A.
S.; Chandrasekara, S. Org. Lett. 2002, 4, 773e775; (c) Ramtohup, Y. K.; James, M.
N. G.; Vederas, J. C. J. Org. Chem. 2002, 67, 3169e3318; (d) Mosaddegh, E.; Has-
sankhani, A. Tetrahedron Lett. 2011, 52, 488e490; (e) Fazaeli, R.; Aliyan, H.; Fa-
zaeli, N. Open Catal. J. 2010, 3, 14e18; (f) Karthikeyan, G.; Pandurangan, A. J. Mol.
Catal. A: Chem. 2012, 361, 58e67; (g) Ghorbani-Vaghei, R.; Karimi-Nami, R.;
Toghraei-Semiromi, Z.; Amiri, M.; Ghavidel, M. Tetrahedron 2011, 67, 1930e1937;
(h) Gaurav, S.; Rajiv, K. V.; Girijesh, K. V.; Shankar Singh, M. Tetrahedron Lett.
2011, 52, 7195e7198; (i) Ramin, G.; Somayyeh, A.; Maryam, S.; Ayoob, B. Tetra-
hedron Lett. 2008, 49, 4479e4482; (j) Veeranarayana Reddy, M.; Chandra Sekhar
Reddy, G.; Yeon Tae, J. Tetrahedron 2012, 68, 6820e6828; (k) Mazaahir, K.; Anwar,
J.; Ritika, C.; Neeraj Kumar, M. Tetrahedron Lett. 2012, 53, 1728e1731; (l) Shirin,
S.; Mohammadpoor-Baltork, I.; Ahmad Reza, K.; Moghadam, M.; Shahram, T.;
Valiollah, M. Catal. Sci. Technol. 2013, 3, 2717e2722; (m) Ali Reza, K.; Siamak, N.;
for C20H14N4O4 (MþHþ) 374.1015, found: 374.1013.
4.2.17. 2-((13Z)-5-Benzylidene-1,2,5,6-tetrahydro-2,6-
dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-1,4-dione (4q). Yield
91%; yellow solid; mp 230e232 ꢀC. IR (KBr):
n
¼3390, 3017, 2853,
1H NMR (400 MHz, DMSO-d6):
11.41 (s, 1H), 11.25 (s, 1H), 8.27 (s, 1H), 8.09e8.05 (m, 4H),
7.88e7.85 (m, 2H), 7.51e7.49 (m, 1H), 7.45e7.43 (m, 2H); 13C NMR
(100 MHz, DMSO-d6) 163.4, 161.6, 154.7, 150.2, 133.1, 132.7, 132.6,
1761, 1657, 1639, 1596, 713 cmꢁ1
.
d
d
132.2, 128.1, 128.0, 127.2, 125.5, 125.1, 119.1; HRMS (ESI, m/z): calcd
for C19H12N4O4 (MþHþ) 360.0859, found: 360.0856.
4.2.18. 2-((13Z)-5-(3,4,5-Trimethoxybenzylidene)-1,2,5,6-tetrahydro-
2,6-dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-1,4-dione
(4r). Yield 93%; yellow solid; mp 268e270 ꢀC. IR (KBr):
n
¼3370,
3042, 2847, 1744, 1690, 1646, 1578, 716 cmꢁ1
.
1H NMR (400 MHz,
Please cite this article in press as: Reddy Mudumala, V.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.04.044

8
V. Reddy Mudumala et al. / Tetrahedron xxx (2014) 1e8
Mahboubeh, G.; SeyedJafar, S. J. Mol. Struct. 2013, 1036, 216e225; (n) Teimouri,
N. Synlett 2014, 193e196; (e) Tayebeh, S.; Haman, T.; Fouad, M. Appl. Catal. A:
Gen. 2014, 470, 56e62; (f) Sushobhan, C.; Ganesh Chandra, N.; Subhasis, S.;
Shankar Singh, M. Org. Lett. 2011, 13, 3762e3765; (g) Ismail Abulkalam, A.; Pil-
laiyar, P.; Kasi, P. ACS Sustain. Chem. Eng. 2013, 1, 174e179.
7. (a) Krishnendu, B.; Swapnadeep, J.; Soumen, S.; Umasish, J. Org. Biomol. Chem.
2014, http://dx.doi.org/10.1039/c3ob42292e; (b) Johannes, E M. N. K.; Bernd, P.
Org. Biomol. Chem. 2013, 11, 1271e1279; (c) Shiyong, P.; Lei, W.; Jian, W. Org.
Biomol. Chem. 2012, 10, 225e228; (d) Zhen, L.; Jianquan, H.; Linhong, W.; Xigeng,
Z. Tetrahedron 2012, 68, 1552e1559; (e) Johan, C.; Amandine, G.; Sebastien, R.;
Janine, C. J. Org. Chem. 2013, 78, 10273e10287.
8. (a) Qiuping, D.; Banpeng, C.; Xianjin, L.; Zhenzhen, Z.; Yi-Yuan, P. Green Chem.
2010, 12, 1607e1610; (b) Surya Prakash Rao, H.; Satish, V. RSC Adv. 2012, 2,
6773e6783; (c) Wang, B.; Pinhua, Z.; Yicheng, W. L. Chin. J. Chem. 2010, 28,
2463e2468; (d) Yichao, Z.; Wen, W.; Jian, L.; Feng, W.; Xiufang, Z.; Hongying, Y.;
Weili, Z.; Xiaochun, D. Tetrahedron Lett. 2013, 54, 5849e5852; (e) Xiuli, B.;
Longcheng, H.; Ruiting, L.; Jianquan, H.; Zhengxing, Z.; Xigeng, Z. Tetrahedron
2012, 68, 7960e7965; (f) Roy, B.; Inul, A.; Srikanta, S.; Majumdar, K. C. Tetrahe-
dron Lett. 2012, 53, 5119e5122; (g) Prouiss, K. C.; Nicolaos, A.; Heropoulos, G. A.;
Theodora, C. Ultrasonics Sonochem. 2014, 21, 937e942; (h) Yicheng, Z.; Min, W.;
Pinhua, L.; Lei, W. Org. Lett. 2012, 14, 2206e2209.
M. B. Tetrahedron 2006, 62, 10849e10853; (o) Shanthi, G.; Perumal, P. T. J. Chem.
Sci. 2010, 122, 415e421; (p) Zhang, X.; Li, Y.; Zhang, Z. Tetrahedron 2011, 67,
7426e7430; (q) Wang, J.; Bai, X.; Xu, C.; Wang, Y.; Lin, W.; Zou, Y.; Shi, D. Mol-
ecules 2012, 17, 8674e8686; (r) Chen, H.; Shi, D. Q. J. Heterocycl. Chem. 2013, 50,
56e61.
5. (a) Jaspreet Kaur, R.; Gagandeep, K. Catal. Sci. Technol. 2014, 4, 142e151; (b)
Leonid, G. V.; Alexey, A. F.; Alexey, V. V. Tetrahedron 2014, 70, 551e572; (c) Anqi,
W.; Xiang, L.; Zhongxing, S.; Huanwang, J. Catal. Sci. Technol. 2014, 4, 71e80; (d)
Bin, Z.; Chun, C.; Seh Yong, L.; Mei, D.; Paul, W. S. Tetrahedron 2014, 70, 578e582;
(e) Pethaiah, G.; Pitchaimani, P.; Subbu, P. Tetrahedron Lett. 2014, 55, 329e332; (f)
Radha Krishna Murthi, P.; Rambabua, D.; Basaveswara Rao, M. V.; Manojit, P.
Tetrahedron Lett. 2014, 55, 507e509; (g) Selvaraj, K.; Sathiyamoorthi, S.; Raju, R.
K.; Palani, E.; QaziNaveed, A.; Anil, K. K. ACS Comb. Sci. 2013, 15, 631e638; (h)
Rui-Yun, G.; Zhi-Min, A.; Li-Ping, M.; Rui-Zhi, W.; Hong-Xia, L.; Shu-Xia, W.;
Zhan-Hui, Z. ACS Comb. Sci. 2013, 15, 557e563; (i) Ayoob, B.; Ghaffar, H.; Ramin,
G. ACS Comb. Sci. 2013, 15, 530e534; (j) Ya-Shan, H.; Bharat, D. N.; Ying-Sheng,
C.; Chung-Ming, S. ACS Comb. Sci. 2013, 15, 551e555.
6. (a) Eskandar, K.; Nadiya, K.; Ozra, A. Tetrahedron 2014, 70, 1383e1386; (b) Matiur,
R.; Anirban, S.; Monoranjan, G.; Adinath, M.; Alakananda, H. Tetrahedron Lett.
2014, 55, 235e239; (c) Wang, X.; Shen-yan, L.; Ying-ming, P.; Heng-shan, W.;
Hong, L.; Zhen-feng, C.; Xiao-huan, Q. Org. Lett. 2014, 16, 580e583; (d) Ahmad
Reza, M.; Mohammad Ali, Z.; Shohreh, F.; Abdolkarim, Z.; Ali Reza, P.; RoyaAyazi,
9. (a) Veeranarayana Reddy, M.; Jeong, Y. T. Synlett 2012, 2985e2991; (b)
Veeranarayana Reddy, M.; Jeong, Y. T. Tetrahedron Lett. 2013, 54,
3546e3549.
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Please cite this article in press as: Reddy Mudumala, V.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.04.044