Facile synthesis of pyrimidine-isoxazoline hybrids in a [bmim][PF 6]-water biphasic system

Article abstract of DOI:10.1055/s-0030-1260099

The convenient synthesis of a library of pyrimidine-isoxazoline hybrids in 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim][PF₆])-water/ potassium hydroxide at ambient temperature has been accomplished. The ionic liquid [bmim][PF₆

Full text of DOI:10.1055/s-0030-1260099

2644
PAPER
Facile Synthesis of Pyrimidine–Isoxazoline Hybrids in a [bmim][PF6]–Water
Biphasic System
P
yrimidine–Isoxaz
u
oline
H
ybrid
s
s
hal Lanjewar,a Anjali Rahatgaonkar,*a Mukund Chorghade,b Binda Sarafa
a
Chemistry Department, Institute of Science, Civil Lines, Nagpur 440001, MS, India
E-mail: anjali_rahatgaonkar@yahoo.com
b
Chorghade Enterprises, 14 Carlson Circle, Natick, MA 01760-4205, USA
Received 25 March 2011; revised 5 May 2011
thesis. 1,3-Dipolar cycloadditions of nitrile oxides to var-
ious dipolarophiles23 have been considerably accelerated
Abstract: The convenient synthesis of a library of pyrimidine–
isoxazoline hybrids in 1-butyl-3-methylimidazolium hexafluoro-
phosphate ([bmim][PF6])–water/potassium hydroxide at ambient
temperature has been accomplished. The ionic liquid [bmim][PF6],
in
1-butyl-3-methylimidazolium
tetrafluoroborate
([bmim][BF4])24 or 1-butyl-3-methylimidazolium hexa-
immiscible in water, can be easily recycled for reuse after separa- fluorophosphate ([bmim][PF6]).25 The most convenient
tion of the products without any noticeable diminution in its activi-
syntheses of isoxazolines have usually been in solvents
ty. The protocol is rapid, the yields are good to excellent, and the
method is facile.
such as dichloromethane, chloroform at 65 °C, methanol–
sodium hydroxide at 80 °C, toluene at 80 °C, N,N-dimeth-
ylformamide, and ethanol–sodium hydroxide.
Key words: pyrimidines, dihydroisoxazoles, ionic liquids, water,
biphasic systems
The hydrophobic ionic liquid [bmim][PF6] is well known
for its capability in various catalytic applications. In par-
ticular, hydrophobic media possessing hexafluorophos-
Isoxazoles and their dihydro derivatives, isoxazolines,
phate anions have a multitude of uses in different
constitute an interesting heterocyclic family with diverse
biochemical and chemical reactions.26
and defined therapeutic significance.1 Such compounds
We have investigated the effect of different reaction con-
ditions involving model hydrophobic ionic liquids, such
as [bmim][PF6], on the formation of isoxazolines, and we
illustrate herein the extension of the use of [bmim][PF6] to
reactions of diversely substituted substrates. The possibil-
ity of adjusting solubility properties using [bmim][PF6]
combinations allows the systematic optimization of the
productivity of the biphasic reaction.
exhibit analgesic, antimicrobial, antifungal, and antican-
cer activities. They are useful intermediates for the syn-
thesis of a variety of bioactive natural products,2 and they
have also served as lead structures for new glutamic acid
ligand receptor designs,3 such as ionotropic (iGluRs) and
metabotropic Glu receptors (mGluRs).
Several methods have been developed for the synthesis of
isoxazolines or isoxazoles, such as the reaction of hydrox-
ylamine with 1,3-dicarbonyl compounds,4 a,b-unsaturat-
ed carbonyl compounds,5 and a,b-unsaturated nitriles.6
Previous reports reveal interesting methods for the syn-
thesis of isoxazolines, e.g. 1,3-dipolar additions,7 a photo-
chemical reaction with nitrosonium tetrafluoroborate as
catalyst,8 solid-phase 1,3-dipolar cycloadditions,9 synthe-
ses of structurally diverse isoxazolines and isoxazoles in
Magtrieve (CrO2),10 and ultrasound-promoted synthesis in
water.11 The synthesis of semisynthetic steroidal
[16a,17a-d]-isoxazolines in the presence of chloramine-T
in refluxing ethanol has been reported.12 A tandem oxima-
tion–cyclization route to D2-isoxazolines in ethanol–sodi-
um hydroxide13 has also been explored.
We embarked on the synthesis of pyrimidine–isoxazoline
hybrid compounds via the cyclocondensation of a,b-un-
saturated carbonyl compounds with hydroxylamine hy-
drochloride. Several reaction conditions were explored in
a diverse array of solvent systems. Few approaches have
been used for the synthesis of heterocycles containing
both isoxazoline and pyrimidine nuclei within a single
molecular framework in ionic liquid–water biphasic sys-
tems. In our synthesis, described below, the model start-
ing material 6-methyl-4-phenyl-5-(3-phenylacryloyl)-
3,4-dihydropyrimidin-2(1H)-one was completely con-
sumed after two hours when the reaction was conducted in
a
[bmim][PF6]–water/potassium hydroxide biphasic
solvent system; the corresponding product, 6-methyl-4-
phenyl-5-(5-phenyl-4,5-dihydroisoxazol-3-yl)-3,4-dihy-
dropyrimidin-2(1H)-one, was formed in high yield. As
previously reported in the literature, the reaction rate was
sluggish in organic solvents. Our efforts at generating a
representative library of isoxazolines using different con-
centrations of [bmim][PF6] in biphasic solvent systems
with addition of catalytic quantities of base are presented
here, and our observations prompted us to explore the po-
tential use of [bmim][PF6]–water and potassium hydrox-
ide.
A wide variety of reagents, such as chlorine,14 N-bromo-15
and N-chlorosuccinimide,16 sodium hypochlorite,17 alkyl
hypochlorites,18 chloramine-T,19 1-chlorobenzotriazole,20
benzyltrimethylammonium tetrachloroiodate,21 and N-
tert-butyl-N-chlorocyanamide,22 have been used for the
chloramination of aldoximes leading to isoxazoline syn-
SYNTHESIS 2011, No. 16, pp 2644–2650
x
x.
x
x
.
2
0
1
1
Advanced online publication: 27.07.2011
DOI: 10.1055/s-0030-1260099; Art ID: M32611SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Pyrimidine–Isoxazoline Hybrids
2645
Initially, 3,4-dihydropyrimidin-2(1H)-one 1a was chosen ylformamide–water at reflux for 15 hours (entries 5 and 6,
as a model substrate in the reaction to give isoxazolines, respectively); the latter reaction resulted in a 56% yield,
forming
isoxazol-3-yl)-3,4-dihydropyrimidin-2(1H)-one
6-methyl-4-phenyl-5-(5-phenyl-4,5-dihydro- indicating a preference for protic conditions.
(2a)
Additionally, the reactions in the ionic liquids triethylam-
monium sulfate ([Et3NH][HSO4] functions dually as sol-
vent and catalyst), [bmim][PF6], [bmim][PF6]–water, and
[bmim][PF6]–water/potassium hydroxide were monitored
over various periods (entries 7–10, respectively); the reac-
tions took place at ambient temperature in these ionic liq-
uids. The use of [bmim][PF6]–water/potassium hydroxide
(entry 10) resulted in much higher reaction rates than
those of the reactions performed in the other ionic liquid
containing solvent systems (entries 7–9). Remarkably, it
was observed that the reaction of substrate 1a proceeded
better in ionic liquids (entries 7–10) compared with that
performed in common organic solvents (entries 1–6). The
reaction in [bmim][PF6]–water/potassium hydroxide un-
questionably showed the highest levels of efficacy and
atom economy compared with the reactions in the other
solvents. In addition, the use of water as a secondary sol-
vent in all the protic, aprotic, and ionic liquid systems im-
proved the isolated yield. Using a catalytic amount of a
base, a remarkable effect on the efficiency of the reaction
in the solvent systems was also observed. Table 1 summa-
rizes our results, clearly showing the superiority of an
ionic liquid–water/potassium hydroxide biphasic system
over an organic solvent–water system.
(Scheme 1). To optimize the reaction conditions, com-
pound 1a was subjected to the reaction with hydroxyl-
amine hydrochloride in various solvents and over
different periods to afford the corresponding pyrimidine–
isoxazoline hybrid 2a (Table 1).
C
A
B
A
B
C
NH2OH•HCl
O
D
N
HN
HN
O
X
N
H
X
N
H
1a
2a
Scheme 1 Synthesis of pyrimidine–isoxazoline hybrid 2a
The reaction of 1a in ethanol with a catalytic amount of
potassium hydroxide at reflux was complete within 15
hours, giving 2a in 65% isolated yield (Table 1, entry 1).
The reaction time was carefully regulated to avoid the de-
composition of the product and the formation of byprod-
ucts. It was observed that the reaction proceeded well on
the addition of a small amount of water: the yield im-
proved to 70% (entry 2). Thus, the efficiency of the reac-
tion was markedly influenced by the nature of the solvent,
i.e. by increasing the hydrophilicity of the reaction mix-
ture. Further, the reaction in acetic acid and acetic acid–
water at reflux for 15 hours diminished the yield (entries
3 and 4, respectively); however, using the latter solvent,
the yield obtained was slightly higher than that achieved
using the former solvent. The yield of 2a was drastically
reduced using N,N-dimethylformamide and N,N-dimeth-
The course of the reaction was monitored by thin-layer
chromatography (TLC), but we found that for all early ex-
periments, TLC or high-performance liquid chromatogra-
phy was not an optimal choice for the evaluation of yields
or for a quantitative in-process assay. The viscous solu-
tion containing water and ionic liquids was not conducive
to TLC and considerable streaking was discerned. We re-
sorted to quenching the reactions and isolating the report-
ed products. All elemental analyses were conducted on
Table 1 Optimization of the Reaction Conditions for the Synthesis of 6-Methyl-4-phenyl-5-(5-phenyl-4,5-dihydroisoxazol-3-yl)-3,4-dihy-
dropyrimidin-2(1H)-one (2a)
Entry
Solvent
Temp
Final isolated yield (%) at a given time
1 h
10
13
12
11
09
10
15
29
37
50
2 h
22
21
26
19
24
26
32
48
59
93
3 h
29
34
38
26
35
38
50
68
87
93
5 h
40
51
49
36
48
46
75
87
87
93
10 h
55
66
60
51
55
50
76
88
89
93
15 h
65
70
61
62
53
56
77
88
90
93
1
2
EtOH/KOH
reflux
reflux
reflux
reflux
reflux
reflux
r.t.
EtOH–H2O/KOH
AcOH
3
4
AcOH–H2O
5
DMF
6
DMF–H2O
7
[Et3NH][HSO4]
[bmim][PF6]
[bmim][PF6]–H2O
[bmim][PF6]–H2O/KOH
8
r.t.
9
r.t.
10
r.t.
Synthesis 2011, No. 16, 2644–2650 © Thieme Stuttgart · New York

2646
K. Lanjewar et al.
PAPER
isolated and purified compounds, and the yields were cal- strates with electron-withdrawing groups at the para posi-
culated based on the quantities of these final products.
tions of rings A (R1) and C (R3) (Table 2, entries 10, 11
and 12 vs entries 4 and 7, and entries 3 and 6 vs entry 2)
displayed enhanced yields ranging from 90–92%. Thus,
electron-withdrawing groups exert better influence than
electron-donating substituents in enhancing the efficacy
and yields of the reaction.
We extended our investigation to the reactions of other
substrates by introducing various substituents to rings A
and C of the molecular framework of 1; we also looked at
related thione derivatives (Table 2).
Table 2 Synthesis of Substituted 5-(4,5-Dihydroisoxazol-3-yl)-6-
methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-ones and Related
Thione Derivatives 2
To verify the impact of the concentration of [bmim][PF6]
on the efficiency of the reaction, we gradually increased
the quantity of [bmim][PF6] from 1 to 15 millimoles while
keeping the amount of water constant at 30 millimoles in
reactions conducted at room temperature for two hours
(Table 3). It was observed that as the concentration of
[bmim][PF6] in water increased, the efficiency of the re-
action also increased. Variations in yield were observed;
albeit minor, these prompted us to reproduce the proce-
dure several times. We established that the variations in
yield were not attributable to losses from workup. Beyond
the use of 10 millimoles of [bmim][PF6], the efficiency of
the reaction decreased, suggesting that the nonpolar or-
ganic hydrophobic tail of the ionic liquid may interfere
with the reaction mechanism.
R3
R1
A
R1
A
C
O
R3
R2
Hc
C
NH2OH•HCl
O
D
N
[bmim][PF6]–H2O, KOH
stirring, r.t.
R2
HN
HN
Hb
B
B
Ha
X
N
H
X
N
H
1
2
Entry
1
Product R1
R2
H
H
H
H
H
H
H
H
Cl
H
H
Cl
H
H
Cl
H
H
Cl
R3
X
Yielda (%)
93
2a
2b
2c
2d
2e
2f
H
H
O
O
O
O
O
O
O
Balanced hydrophobic–hydrophilic solvent interactions
have been observed. Increased yields were noted on the
addition of measured amounts of water to all solvent sys-
tems (vide supra), suggesting that an environment of polar
or protic solvents is more conducive to the reaction.
2
H
OMe
Cl
85
3
H
89
4
OMe
OMe
OMe
OH
OH
OH
Cl
H
87
5
OMe
Cl
88
Table 3 Effect of Varying the Concentration of the Ionic Liquid
[bmim][PF6] in Water/KOH for the Synthesis of 6-Methyl-4-phenyl-
5-(5-phenyl-4,5-dihydroisoxazol-3-yl)-3,4-dihydropyrimidin-2(1H)-
one (2a)a
6
92
7
2g
2h
2i
H
82
Entry
[bmim][PF6] (mmol)
Yield (%)
8
OMe
H
O
O
O
O
O
S
84
1
2
3
4
5
6
1
3
81
85
89
93
90
87
9
88
10
11
12
13
14
15
16
17
18
2j
H
90
7
2k
2l
Cl
OMe
H
89
10
13
15
Cl
90
2m
2n
2o
2p
2q
2r
H
H
89
H
OMe
H
S
85
a With H2O (30 mmol) and KOH (1 mmol) at r.t. for 2 h.
H
S
90
OMe
OMe
OMe
H
S
86
Interestingly, the ionic liquid–water biphasic system
[bmim][PF6]–water/potassium hydroxide proved to be ex-
ceptionally effective at enhancing the efficiency of the re-
action. The ionic liquid [bmim][PF6] is used in a biphasic
system as a substrate reservoir for substrates that are poor-
ly soluble in water–organic solvent mixtures. A plausible
explanation of the reaction mechanism in the ionic liquid–
water biphasic system is as follows: The ionic liquid
[bmim][PF6] is hydrophobic and immiscible with water.
One of the reactants, the pyrimidinone, e.g. 1a, is hydro-
phobic while hydroxylamine hydrochloride is hydrophilic
in nature. The different solvation affinities of these two re-
actants retard the reaction. The [bmim][PF6]–water/potas-
OMe
H
S
85
S
90
a Isolated yield.
The incorporation of electron-donating substituents at the
para-position of ring A (R1) resulted in a slight decrease
in the yield (Table 2, entries 4 and 7 vs entry 1, and entry
16 vs entry 13). Electron-donating substituents at ring C
(R3) showed a very slight increase in reaction efficiency
(Table 2, entry 5 vs entry 4 and entry 8 vs entry 7). Sub-
Synthesis 2011, No. 16, 2644–2650 © Thieme Stuttgart · New York

PAPER
Pyrimidine–Isoxazoline Hybrids
2647
sium hydroxide solvent system provides a platform for the was flushed out with water and reused directly without
nonpolar organic counterpart [bmim]+ to easily make 1a further purification and without great diminution of the
soluble; [PF6]– and the water/potassium hydroxide coun- yields in up to 10 reaction cycles; however, there was a
terpart make hydroxylamine hydrochloride soluble. The noticeable drop in yield after the 10th cycle, suggesting
free hydroxylamine, produced in situ in the aqueous phase that the catalyst may have become contaminated, degrad-
by the reaction of hydroxylamine hydrochloride and po- ed, or exhausted (Table 4). Our protocol has the merit of
tassium hydroxide, is transported to the ionic liquid phase being environmentally benign and a simple operation, in-
where the reaction may occur at the junction of the two volving convenient workup, a short reaction time, and
immiscible solvents (Scheme 2). This suggests that the proceeding in good to excellent yields.
ionic liquid biphasic system effectively delivers the sub-
strates at the interface of two immiscible liquids.
Contributing to the elucidation of the structures of com-
pounds 2a–r (see Table 2), their infrared spectra showed
a peak at 519–526 cm–1 owing to C=N stretching of the
isoxazoline ring and peaks at 828–835 and 968–974 cm–1
_
because of N–O and C–O–N stretching, respectively, of
PF6
+
N
N
the isoxazoline ring. Furthermore, the 1H NMR spectra of
compounds 2a–r showed a singlet of three protons at d =
2.04–2.20 ppm owing to the ArCH3 protons. In the isox-
azoline ring there are three types of hydrogen, one at-
tached to the C-5 carbon, i.e. Hc, and two at C-4. The two
hydrogens attached at the 4-position are cis and trans Ha
and Hb, respectively. The 1H NMR spectra for model com-
pound 2a showed a doublet at d = 2.59–2.61 ppm owing
to the Ha proton. Proton Hb coupled with both Ha and Hc
to give a double doublet at d = 3.19–3.22 ppm. The dou-
blet at d = 5.09–5.13 ppm owing to the Hc proton confirms
the structure of the isoxazoline ring. A signal owing to the
proton in a hydroxy group appeared at d = 10.50–10.53
ppm in the spectra of compounds 2g–i. In addition, the
three protons of the methoxy group in compounds 2b, 2d–
f, 2h, 2k, 2n, and 2p–r resonated as a singlet at d = 3.78–
3.87 ppm. The 13C NMR spectra also support the struc-
tures of the products; signals at d = 25.4–28.0, 72.0–82.2,
and 155.6–161.2 ppm indicated the presence of an isox-
azoline ring. Satisfactory elemental analyses were ob-
tained for compounds 2a–r, and the mass spectral data
also lent credence to the assigned structures.
1a
NH2OH
KOH
NH2OH⋅HCl
aqueous phase
Scheme 2 A plausible reaction mechanism in an ionic liquid–water
biphasic system
For each reaction, we have optimized the extraction and
isolation of the resulting product in the ionic liquid phase
using various solvents, such as diethyl ether, dichloro-
methane, ethyl acetate, and n-hexane; the best results were
obtained with diethyl ether and this was the solvent of
choice for further experiments. Inorganic salts, formed as
byproducts, dissolved in water. The separated ionic liquid
Table 4 Effect of the Reuse of the Ionic Liquid [bmim][PF6] on the
Formation of 6-Methyl-4-phenyl-5-(5-phenyl-4,5-dihydroisoxazol-
3-yl)-3,4-dihydropyrimidin-2(1H)-one (2a)
In conclusion, [bmim][PF6]–water/potassium hydroxide
proved to be an exceptionally efficient biphasic solvent
system for the synthesis of pyrimidine–isoxazoline hy-
brids at ambient temperature within two hours. The proto-
col has the merit of being environmentally friendly and a
simple operation, involving convenient workup, a short
reaction time, and resulting in good to excellent yields.
The ionic liquid [bmim][PF6] can be reused in up to 10 re-
action cycles, but after this the loss of its activity has been
observed. The reaction is influenced by aqueous potassi-
um hydroxide. The ionic liquid [bmim][PF6] stabilizes the
hydrophobic reactant, and water stabilizes hydroxylamine
hydrochloride; the reaction presumably occurs at the junc-
tion of the two immiscible phases.
Entry
1
Ionic liquid recycling
Yield (%)
93
0
1
2
92
3
2
92
4
3
91
5
4
91
6
5
90
7
6
89
8
7
87
9
8
85
All solvents were distilled prior to use. Thin-layer chromatography
was performed on silica gel G (Qualigen). Melting points were de-
termined by the open capillary method and are uncorrected. H
NMR spectra were recorded in DMSO-d6 on a Bruker Avance II
400 NMR spectrometer and 13C NMR spectra were recorded in
CDCl3 on a Varian Mercury YH-300 spectrometer. Chemical shifts
are reported using TMS as an internal standard. The IR spectra were
obtained on a Shimadzu FT-IR spectrophotometer using KBr discs.
10
11
12
13
9
81
1
10
11
12
75
67
55
Synthesis 2011, No. 16, 2644–2650 © Thieme Stuttgart · New York

2648
K. Lanjewar et al.
PAPER
4-(4-Methoxyphenyl)-6-methyl-5-(5-phenyl-4,5-dihydroisox-
azol-3-yl)-3,4-dihydropyrimidin-2(1H)-one (2d)
Yield: 950 mg (87%); yellow solid; mp 173 °C.
Mass spectra were recorded using a Shimadzu gas chromatograph.
Elemental analyses were performed on a Perkin-Elmer 2400 instru-
ment.
IR (KBr): 521, 830, 973 cm–1.
6-Methyl-4-phenyl-5-(5-phenyl-4,5-dihydroisoxazol-3-yl)-3,4-
dihydropyrimidin-2(1H)-one (2a); Typical Procedure
1H NMR (400 MHz, DMSO-d6): d = 2.20 (s, 3 H, ArCH3), 2.61–
2.63 (d, J = 8.2 Hz, 1 H, Ha), 3.23–3.28 (dd, J = 9.7, 8.6 Hz, 1 H,
Hb), 3.78 (s, 3 H, OCH3), 4.91 (s, 1 H, CH), 5.06–5.09 (d, J = 12.6
Hz, 1 H, Hc), 6.45 (s, 1 H, NH), 7.10–7.50 (m, 9 H, ArH), 7.68 (s, 1
H, NH).
13C NMR (75 MHz, CDCl3): d = 18.4, 27.0, 46.4, 55.8, 82.0, 109.6,
113.8, 127.0, 127.4, 128.2, 129.6, 134.0, 141.4, 144.2, 150.8, 155.0,
159.6.
A mixture of 6-methyl-4-phenyl-5-(3-phenylacryloyl)-3,4-dihydro-
pyrimidin-2(1H)-one (1a) (0.95 g, 3 mmol), hydroxylamine hydro-
chloride (0.28 g, 4 mmol), and KOH (0.056 g, 1 mmol) was
introduced to a vigorously stirred mixture of the [bmim][PF6] (2.84
g, 2 mL, 10 mmol) and H2O (0.54 g, 30 mmol) biphasic solvent sys-
tem at r.t., and stirring was continued for 2 h. The course of reaction
was monitored by TLC. After completion, the reaction was
quenched with H2O (5 mL), and the immiscible ionic liquid
[bmim][PF6] layer was separated from the aqueous phase and ex-
tracted with Et2O (3 × 10 mL). The organic layer was dried (anhyd
Na2SO4) and then concentrated in vacuo to afford the pure product
as a yellow solid. Yield: 0.92 g (93%); mp 148 °C.
GC-MS (70 eV): m/z = 363 [M+].
Anal. Calcd for C21H21N3O3: C, 69.42; H, 5.78; N, 11.57. Found: C,
69.38; H, 5.67; N, 11.49.
4-(4-Methoxyphenyl)-5-[5-(4-methoxyphenyl)-4,5-dihydroisox-
azol-3-yl]-6-methyl-3,4-dihydropyrimidin-2(1H)-one (2e)
Yield: 1040 mg (88%); yellow solid; mp 160 °C.
IR (KBr): 519, 829, 972 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 2.10 (s, 3 H, ArCH3), 2.63–
2.65 (d, J = 8.4 Hz, 1 H, Ha), 3.23–3.29 (dd, J = 9.7, 8.6 Hz, 1 H,
Hb), 3.79 (s, 3 H, OCH3), 3.83 (s, 3 H, OCH3), 4.91 (s, 1 H, CH),
5.07–5.09 (d, J = 11.0 Hz, 1 H, Hc), 7.08 (s, 1 H, NH), 7.30–7.51
(m, 8 H, ArH), 7.68 (s, 1 H, NH).
The recycled ionic liquid was reused in the next reaction without
any noticeable effect on the results.
IR (KBr): 522, 831, 970 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 2.12 (s, 3 H, ArCH3), 2.59–
2.61 (d, J = 7.4 Hz, 1 H, Ha), 3.19–3.22 (dd, J = 8.8, 2.3 Hz, 1 H,
Hb), 4.98 (s, 1 H, CH), 5.09–5.13 (d, J = 10.3 Hz, 1 H, Hc), 6.68 (s,
1 H, NH), 6.82–7.48 (m, 10 H, ArH), 7.96 (s, 1 H, NH).
13C NMR (75 MHz, CDCl3): d = 18.4, 27.0, 46.8, 82.0, 110.2, 126.2,
127.0, 127.9, 129.6, 140.2, 143.8, 144.4, 150.8, 155.6.
GC-MS (70 eV): m/z = 333 [M+].
13C NMR (75 MHz, CDCl3): d = 16.0, 26.2, 47.2, 55.8, 81.0, 109.4,
113.8, 114.0, 127.2, 132.0, 133.8, 144.0, 150.6, 154.8, 159.4, 159.6.
GC-MS (70 eV): m/z = 393 [M+].
Anal. Calcd for C20H19N3O2: C, 72.07; H, 5.72; N, 12.61. Found: C,
72.01; H, 5.62; N, 12.55.
Anal. Calcd for C22H23N3O4: C, 67.17; H, 5.85; N, 10.68. Found: C,
66.99; H, 5.82; N, 10.61.
5-[5-(4-Methoxyphenyl)-4,5-dihydroisoxazol-3-yl]-6-methyl-4-
phenyl-3,4-dihydropyrimidin-2(1H)-one (2b)
Yield: 930 mg (85%); yellow solid; mp 112 °C.
IR (KBr): 521, 833, 971 cm–1.
5-[5-(4-Chlorophenyl)-4,5-dihydroisoxazol-3-yl]-4-(4-methoxy-
phenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (2f)
Yield: 1100 mg (92%); yellow solid; mp 148 °C.
1H NMR (400 MHz, DMSO-d6): d = 2.17 (s, 3 H, ArCH3), 2.57–
2.59 (d, J = 8.5 Hz, 1 H, Ha), 3.22–3.29 (dd, J = 8.4, 6.4 Hz, 1 H,
Hb), 3.82 (s, 3 H, OCH3), 4.96 (s, 1 H, CH), 5.08–5.10 (d, J = 10.3
Hz, 1 H, Hc), 6.42 (s, 1 H, NH), 6.62–7.44 (m, 9 H, ArH), 8.00 (s, 1
H, NH).
13C NMR (75 MHz, CDCl3): d = 17.2, 26.8, 46.4, 55.8, 82.0, 109.4,
113.6, 126.4, 126.8, 128.0, 134.0, 143.8, 144.2, 150.6, 155.2, 161.2.
IR (KBr): 524, 830, 968 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 2.04 (s, 3 H, ArCH3), 2.60–
2.62 (d, J = 7.0 Hz, 1 H, Ha), 3.26–3.29 (dd, J = 7.2, 7.2 Hz, 1 H,
Hb), 3.82 (s, 3 H, OCH3), 4.88 (s, 1 H, CH), 5.11–5.14 (d, J = 11.1
Hz, 1 H, Hc), 7.02 (s, 1 H, NH), 7.10–7.44 (m, 8 H, ArH), 7.56 (s, 1
H, NH).
13C NMR (75 MHz, CDCl3): d = 15.8, 25.8, 47.2, 55.8, 81.9, 108.8,
113.6, 127.0, 128.0, 133.8, 134.0, 138.6, 144.2, 150.2, 154.0, 159.2.
GC-MS (70 eV): m/z = 363 [M+].
GC-MS (70 eV): m/z = 397 [M+].
Anal. Calcd for C21H21N3O3: C, 69.42; H, 5.78; N, 11.57. Found: C,
69.33; H, 5.64; N, 11.43.
Anal. Calcd for C21H20N3O3Cl: C, 63.47; H, 5.03; N, 10.57. Found:
C, 63.32; H, 4.91; N, 10.43.
5-[5-(4-Chlorophenyl)-4,5-dihydroisoxazol-3-yl]-6-methyl-4-
phenyl-3,4-dihydropyrimidin-2(1H)-one (2c)
Yield: 980 mg (89%); yellow solid; mp 150 °C.
IR (KBr): 520, 832, 969 cm–1.
4-(4-Hydroxyphenyl)-6-methyl-5-(5-phenyl-4,5-dihydroisox-
azol-3-yl)-3,4-dihydropyrimidin-2(1H)-one (2g)
Yield: 860 mg (82%); yellow solid; mp 172 °C.
1H NMR (400 MHz, DMSO-d6): d = 2.19 (s, 3 H, ArCH3), 2.62–
2.64 (d, J = 8.6 Hz, 1 H, Ha), 3.22–3.29 (dd, J = 8.0, 7.4 Hz, 1 H,
Hb), 4.90 (s, 1 H, CH), 5.05–5.08 (d, J = 11.6 Hz, 1 H, Hc), 6.71 (s,
1 H, NH), 7.00–7.44 (m, 9 H, ArH), 7.86 (s, 1 H, NH).
13C NMR (75 MHz, CDCl3): d = 17.8, 26.8, 47.4, 80.2, 108.2, 126.0,
126.6, 128.0, 129.2, 132.4, 137.4, 143.8, 144.0, 151.0, 155.2.
IR (KBr): 520, 828, 968 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.11 (s, 3 H, ArCH3), 2.51–2.53
(d, J = 8.56 Hz, 1 H, Ha), 3.11–3.16 (dd, J = 7.4, 8.6 Hz, 1 H, Hb),
4.80 (s, 1 H, CH), 5.21–5.23 (d, J = 10.96 Hz, 1 H, Hc), 6.68 (s, 1
H, NH), 7.10–7.68 (m, 9 H, ArH), 7.70 (s, 1 H, NH), 10.50 (s, 1 H,
OH).
13C NMR (75 MHz, CDCl3): d = 17.4, 27.8, 47.0, 81.8, 108.0, 115.8,
126.8, 127.0, 127.4, 128.8, 130.6, 140.0, 144.0, 150.6, 155.0, 155.8.
GC-MS (70 eV): m/z = 367 [M+].
Anal. Calcd. for C20H18N3O2Cl: C, 65.39; H, 4.90; N, 11.44. Found:
C, 65.29; H, 4.79; N, 11.42.
GC-MS (70 eV): m/z = 349 [M+].
Anal. Calcd for C20H19N3O3: C, 68.76; H, 5.44; N, 12.03. Found: C,
68.61; H, 5.29; N, 11.96.
Synthesis 2011, No. 16, 2644–2650 © Thieme Stuttgart · New York

PAPER
Pyrimidine–Isoxazoline Hybrids
2649
4-(4-Hydroxyphenyl)-5-[5-(4-methoxyphenyl)-4,5-dihydroisox-
azol-3-yl]-6-methyl-3,4-dihydropyrimidin-2(1H)-one (2h)
Yield: 960 mg (84%); yellow solid; mp 180 °C.
4-(4-Chlorophenyl)-5-[5-(2-chlorophenyl)-4,5-dihydroisoxazol-
3-yl]-6-methyl-3,4-dihydropyrimidin-2(1H)-one (2l)
Yield: 1080 mg (90%); yellow solid; mp 158 °C.
IR (KBr): 525, 833, 973 cm–1.
IR (KBr): 523, 834, 972 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.08 (s, 3 H, ArCH3), 2.59–2.61
(d, J = 8.6 Hz, 1 H, Ha), 3.19–3.22 (dd, J = 8.2, 7.0 Hz, 1 H, Hb),
3.85 (s, 3 H, OCH3), 4.77 (s, 1 H, CH), 5.22–5.25 (d, J = 10.6 Hz, 1
H, Hc), 7.12 (s, 1 H, NH), 7.25–7.70 (m, 8 H, ArH), 7.75 (s, 1 H,
NH), 10.53 (s, 1 H, OH).
13C NMR (75 MHz, CDCl3): d = 17.8, 27.8, 47.6, 55.9, 81.0, 108.2,
114.0, 115.2, 128.4, 129.0, 132.6, 135.8, 144.0, 150.6, 155.0, 155.8,
159.8.
1H NMR (400 MHz, DMSO-d6): d = 2.19 (s, 3 H, ArCH3), 2.62–
2.64 (d, J = 7.8 Hz, 1 H, Ha), 3.23–3.27 (dd, J = 7.9, 6.3 Hz, 1 H,
Hb), 4.91 (s, 1 H, CH), 5.07–5.10 (d, J = 11.5 Hz, 1 H, Hc), 7.03 (s,
1 H, NH), 7.12–7.44 (m, 8 H, ArH), 7.55 (s, 1 H, NH).
13C NMR (75 MHz, CDCl3): d = 17.8, 25.6, 48.0, 74.6, 108.8, 127.0,
128.8, 129.8, 130.2, 132.0, 136.6, 142.0, 145.8, 150.4, 156.2.
GC-MS (70 eV): m/z = 401 [M+].
Anal. Calcd for C20H17N3O2Cl2: C, 59.85; H, 4.23; N, 10.47. Found:
C, 59.74; H, 4.20; N, 10.36.
GC-MS (70 eV): m/z = 379 [M+].
Anal. Calcd for C21H21N3O4: C, 66.49; H, 5.54; N, 11.08. Found: C,
66.45; H, 5.42; N, 11.03.
6-Methyl-4-phenyl-5-(5-phenyl-4,5-dihydroisoxazol-3-yl)-3,4-
dihydropyrimidine-2(1H)-thione (2m)
5-[5-(2-Chlorophenyl)-4,5-dihydroisoxazol-3-yl]-4-(4-hydroxy-
phenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (2i)
Yield: 1010 mg (88%); yellow solid; mp 125 °C.
IR (KBr): 521, 835, 969 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.11 (s, 3 H, ArCH3), 2.51–2.53
(d, J = 9.0 Hz, 1 H, Ha), 3.12–3.17 (dd, J = 7.4, 8.6 Hz, 1 H, Hb),
4.80 (s, 1 H, CH), 5.20–5.23 (d, J = 11.4 Hz, 1 H, Hc), 6.68 (s, 1 H,
NH), 7.10–7.68 (m, 8 H, ArH), 7.70 (s, 1 H, NH), 10.50 (s, 1 H,
OH).
Yield: 930 mg (89%); yellow solid; mp 150 °C.
IR (KBr): 522, 833, 971 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 2.12 (s, 3 H, ArCH3), 2.61–
2.63 (d, J = 8.2 Hz, 1 H, Ha), 3.20–3.23 (dd, J = 4.9, 3.5 Hz, 1 H,
Hb), 3.56 (s, 1 H, NH), 4.19 (s, 1 H, NH), 4.97 (s, 1 H, CH), 5.07–
5.10 (d, J = 10.7 Hz, 1 H, Hc), 6.83–7.48 (m, 10 H, ArH).
13C NMR (75 MHz, CDCl3): d = 17.0, 26.4, 52.8, 82.2, 107.8, 126.0,
126.4, 127.2, 129.4, 130.0, 141.8, 144.2, 155.8, 158.0, 181.0.
GC-MS (70 eV): m/z = 349 [M+].
13C NMR (75 MHz, CDCl3): d = 16.4, 25.8, 47.2, 73.0, 108.8, 115.4,
126.4, 127.6, 128.8, 132.0, 134.0, 136.4, 143.8, 150.6, 155.2, 155.8.
GC-MS (70 eV): m/z = 383 [M+].
Anal. Calcd for C20H19N3OS: C, 68.77; H, 5.44; N, 12.03. Found:
C, 68.65; H, 5.36; N, 11.91.
Anal. Calcd for C20H18N3O3Cl: C, 62.66; H, 4.70; N, 10.96. Found:
C, 62.55; H, 4.65; N, 10.89.
5-[5-(4-Methoxyphenyl)-4,5-dihydroisoxazol-3-yl]-6-methyl-4-
phenyl-3,4-dihydropyrimidine-2(1H)-thione (2n)
Yield: 970 mg (85%); yellow solid; mp 138 °C.
4-(4-Chlorophenyl)-6-methyl-5-(5-phenyl-4,5-dihydroisoxazol-
3-yl)-3,4-dihydropyrimidin-2(1H)-one (2j)
Yield: 990 mg (90%); yellow solid; mp 178 °C.
IR (KBr): 524, 832, 972 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 2.09 (s, 3 H, ArCH3), 2.71–
2.73 (d, J = 8.5 Hz, 1 H, Ha), 3.19–3.24 (dd, J = 8.4, 8.4 Hz, 1 H,
Hb), 4.97 (s, 1 H, CH), 5.05–5.08 (d, J = 11.5 Hz, 1 H, Hc), 6.95 (s,
1 H, NH), 7.05–7.41 (m, 9 H, ArH), 7.58 (s, 1 H, NH).
13C NMR (75 MHz, CDCl3): d = 16.2, 25.8, 47.8, 82.0, 109.0, 126.8,
127.2, 129.0, 129.4, 129.8, 132.0, 140.0, 141.4, 145.0, 150.6, 155.2.
IR (KBr): 525, 831, 970 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 2.17 (s, 3 H, ArCH3), 2.57–
2.59 (d, J = 8.6 Hz, 1 H, Ha), 3.24–3.29 (dd, J = 8.4, 7.2 Hz, 1 H,
Hb), 3.55 (s, 1 H, NH), 3.82 (s, 3 H, OCH3), 4.29 (s, 1 H, NH), 4.96
(s, 1 H, CH), 5.08–5.11 (d, J = 15.08 Hz, 1 H, Hc), 6.78–7.44 (m, 9
H, ArH).
13C NMR (75 MHz, CDCl3): d = 18.0, 26.4, 52.0, 55.8, 82.0, 108.0,
115.2, 126.4, 127.2, 128.2, 129.0, 134.2, 144.4, 155.8, 156.8, 159.0,
181.2.
GC-MS (70 eV): m/z = 379 [M+].
GC-MS (70 eV): m/z = 367 [M+].
Anal. Calcd for C21H21N3O2S: C, 66.49; H, 5.54; N, 11.08. Found:
C, 66.25; H, 5.41; N, 10.95.
Anal. Calcd for C20H18N3O2Cl: C, 65.39; H, 4.90; N, 11.44. Found:
C, 65.32; H, 4.87; N, 11.36.
5-[5-(2-Chlorophenyl)-4,5-dihydroisoxazol-3-yl]-6-methyl-4-
phenyl-3,4-dihydropyrimidine-2(1H)-thione (2o)
Yield: 1030 mg (90%); yellow solid; mp 168 °C.
IR (KBr): 522, 830, 974 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 2.19 (s, 3 H, ArCH3), 2.60–
2.62 (d, J = 8.2 Hz, 1 H, Ha), 3.23–3.29 (dd, J = 8.0, 7.4 Hz, 1 H,
Hb), 3.54 (s, 1 H, NH), 4.20 (s, 1 H, NH), 4.90 (s, 1 H, CH), 5.06–
5.09 (d, J = 11.5 Hz, 1 H, Hc), 7.00–7.44 (m, 9 H, ArH).
13C NMR (75 MHz, CDCl3): d = 17.8, 26.8, 52.6, 72.0, 108.4, 126.6,
127.8, 128.6, 129.8, 133.4, 137.8, 143.6, 155.6, 160.0, 181.2.
GC-MS (70 eV): m/z = 383 [M+].
4-(4-Chlorophenyl)-5-[5-(4-methoxyphenyl)-4,5-dihydroisox-
azol-3-yl]-6-methyl-3,4-dihydropyrimidin-2(1H)-one (2k)
Yield: 1060 mg (89%); yellow solid; mp 168 °C.
IR (KBr): 519, 829, 968 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 2.19 (s, 3 H, ArCH3), 2.63–
2.65 (d, J = 8.6 Hz, 1 H, Ha), 3.23–3.29 (dd, J = 8.0, 7.4 Hz, 1 H,
Hb), 3.87 (s, 3 H, OCH3), 4.90 (s, 1 H, CH), 5.06–5.09 (d, J = 11.1
Hz, 1 H, Hc), 6.78 (s, 1 H, NH), 7.07–7.39 (m, 8 H, ArH), 7.86 (s, 1
H, NH).
13C NMR (75 MHz, CDCl3): d = 16.4, 25.8, 47.2, 57.0, 81.9, 108.8,
115.8, 127.8, 128.0, 128.4, 128.8, 132.0, 134.4, 141.8, 145.6, 150.6,
155.2, 160.6.
Anal. Calcd for C20H18N3OSCl: C, 62.66; H, 4.70; N, 10.97. Found:
C, 62.53; H, 4.57; N, 10.88.
GC-MS (70 eV): m/z = 397 [M+].
Anal. Calcd for C21H20N3O3Cl: C, 63.47; H, 5.03; N, 10.58. Found:
C, 63.38; H, 5.01; N, 10.45.
Synthesis 2011, No. 16, 2644–2650 © Thieme Stuttgart · New York

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K. Lanjewar et al.
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4-(4-Methoxyphenyl)-6-methyl-5-(5-phenyl-4,5-dihydroisox-
azol-3-yl)-3,4-dihydropyrimidine-2(1H)-thione (2p)
Yield: 980 mg (86%); yellow solid; mp 160 °C.
IR (KBr): 526, 831, 972 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 2.17 (s, 3 H, ArCH3), 2.23–
2.25 (d, J = 5.8 Hz, 1 H, Ha,), 3.23–3.29 (dd, J = 8.4, 6.4 Hz, 1 H,
Hb), 3.55 (s, 1 H, NH), 3.82 (s, 3 H, OCH3), 4.35 (s, 1 H, NH), 4.96
(s, 1 H, CH), 5.07–5.10 (d, J = 11.0 Hz, 1 H, Hc), 6.87–7.44 (m, 9
H, ArH).
References
(1) Gaonkar, S. L.; Lokanatha Rai, K. M.; Prabhuswamy, B.
Med. Chem. Res. 2007, 15, 407.
(2) (a) Zificsak, C. A.; Hlasta, D. J. Tetrahedron 2004, 60,
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(4) Hansen, T. V.; Wu, P.; Fokin, V. V. J. Org. Chem. 2005, 70,
7761.
13C NMR (75 MHz, CDCl3): d = 18.2, 28.0, 53.0, 55.8, 82.2, 107.6,
115.0, 127.8, 129.8, 130.6, 135.8, 140.8, 156.0, 158.0, 159.4, 181.2.
GC-MS (70 eV): m/z = 379 [M+].
(5) Waldo, J. P.; Larock, R. C. Org. Lett. 2005, 7, 5203.
(6) Vicentini, C. B.; Verones, A. C.; Poli, T.; Guameri, M.;
Gioni, P.; Ferreti, V. J. Heterocycl. Chem. 1990, 27, 1481.
(7) Higashida, S.; Nakashima, H.; Tohda, Y.; Tani, K.;
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Anal. Calcd for C21H21N3O2S: C, 66.49; H, 5.54; N, 11.08. Found:
C, 66.29; H, 5.34; N, 10.88.
4-(4-Methoxyphenyl)-5-[5-(4-methoxyphenyl)-4,5-dihydroisox-
azol-3-yl]-6-methyl-3,4-dihydropyrimidine-2(1H)-thione (2q)
Yield: 1040 mg (85%); yellow solid; mp 165 °C.
IR (KBr): 521, 829, 970 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 2.10 (s, 3 H, ArCH3), 2.62–
2.64 (d, J = 9.7 Hz, 1 H, Ha), 3.23–3.29 (dd, J = 9.7, 8.6 Hz, 1 H,
Hb), 3.37 (s, 1 H, NH), 3.78 (s, 3 H, OCH3), 3.84 (s, 3 H, OCH3),
4.31 (s, 1 H, NH), 4.91 (s, 1 H, CH), 5.07–5.09 (d, J = 11.0 Hz, 1 H,
Hc), 7.29–7.51 (m, 8 H, ArH).
13C NMR (75 MHz, CDCl3): d = 18.0, 27.8, 52.6, 55.8, 56.0, 82.2,
108.0, 115.7, 115.9, 129.4, 133.6, 135.9, 155.0, 157.8, 158.4, 159.6,
181.0.
(9) Shankar, B. B.; Yang, D. Y.; Girton, S.; Ganguly, A. K.
Tetrahedron Lett. 1998, 39, 2447.
(10) Bhosale, S.; Kurhade, S.; Prasad, U. V.; Palle, V. P.;
Bhuniya, D. Tetrahedron Lett. 2009, 50, 3948.
(11) Martins, M. A. P.; Pereira, C. M. P.; Cunico, W.; Moura, S.;
Rosa, F. A.; Peres, R. L.; Machado, P.; Zanatta, N.;
Bonacorso, H. G. Ultrason. Sonochem. 2006, 13, 364.
(12) Chowdhury, P.; Das, A. M.; Goswami, P. Steroids 2005, 70,
494.
(13) Norman, A. L.; Shurrush, K. A.; Calleroz, A. T.; Mosher, M.
D. Tetrahedron Lett. 2007, 48, 6849.
GC-MS (70 eV): m/z = 409 [M+].
(14) (a) Eibler, E.; Kasbauer, J.; Pohl, H.; Sauer, J. Tetrahedron
Lett. 1987, 28, 1097. (b) Corbett, D. F. J. Chem. Soc., Perkin
Trans. 1 1986, 421.
Anal. Calcd for C22H23N3O3S: C, 64.55; H, 5.62; N, 10.27. Found:
C, 64.41; H, 5.48; N, 10.05.
(15) Armstrong, S. K.; Collington, E. W.; Knight, J. G.; Naylorb,
A.; Warren, S. J. Chem. Soc., Perkin Trans. 1 1993, 1433.
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1980, 45, 3916. (b) Gi, H. J.; Xiang, Y.; Schinazi, R. F.;
Zhao, K. J. Org. Chem. 1997, 62, 88.
5-[5-(2-Chlorophenyl)-4,5-dihydroisoxazol-3-yl]-4-(4-meth-
oxyphenyl)-6-methyl-3,4-dihydropyrimidine-2(1H)-thione (2r)
Yield: 1120 mg (90%); yellow solid; mp 184 °C.
IR (KBr): 525, 833, 968 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 2.04 (s, 3 H, ArCH3), 2.60–
2.62 (d, J = 8.2 Hz, 1 H, Ha), 3.26–3.29 (dd, J = 6.6, 5.6 Hz, 1 H,
Hb), 3.49 (s, 1 H, NH), 3.78 (s, 3 H, OCH3), 4.29 (s, 1 H, NH), 4.88
(s, 1 H, CH), 5.13–5.16 (d, J = 11.1 Hz, 1 H, Hc), 7.10–7.44 (m, 8
H, ArH).
13C NMR (75 MHz, CDCl3): d = 17.9, 25.4, 52.6, 55.8, 73.0, 108.4,
115.6, 127.8, 128.0, 129.0, 129.8, 133.9, 136.0, 137.6, 154.6, 155.8,
159.8, 180.8.
(17) Lee, G. A. Synthesis 1982, 508.
(18) Ye, Y.; Zheng, Y.; Xu, G. Y.; Liu, L. Z. Heteroat. Chem.
2003, 14, 254.
(19) Hassner, A.; Lokanatha Rai, K. M. Synthesis 1989, 57.
(20) Kim, J.; Ryu, E. Synth. Commun. 1990, 20, 1373.
(21) Kanemasa, S.; Matsuda, H.; Kamimurac, A.; Kakinamid, T.
Tetrahedron 2000, 56, 1057.
(22) Kumar, V.; Kaushik, M. P. Tetrahedron Lett. 2006, 47,
1457.
(23) Seregin, I. V.; Ovchinnikov, I. V.; Makhova, N. N.;
Lyubetsky, D. V.; Lyssenko, K. A. Mendeleev Commun.
2003, 13, 230.
(24) Armstrong, W.; He, L.; Liu, Y. S. Anal. Chem. 1999, 71,
3873.
GC-MS (70 eV): m/z = 413 [M+].
Anal. Calcd for C21H20N3O2SCl: C, 61.01; H, 4.84; N, 10.17.
Found: C, 60.89; H, 4.78; N, 10.09.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
(25) Suarez, P. A.; Dullius, J. E. L.; Einloft, S.; DeSouza, R. F.;
Dupont, J. Polyhedron 1996, 15, 1217.
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2009, 60, 1.
Acknowledgment
The authors wish to express their gratitude to the Department of
Pharmacy, Nagpur, for IR spectroscopic analysis, the Sophisticated
Analytical Instrumentation Facility (SAIF), Chandigarh, for 1H
NMR spectroscopic analysis, and the University of Pune for 13C
NMR spectroscopic and mass analysis.
Synthesis 2011, No. 16, 2644–2650 © Thieme Stuttgart · New York