A convenient and efficient protocol for the one pot synthesis of 3,4-dihydropyrimidin-2-(1H)-ones catalyzed by ionic liquids under ultrasound irradiation

Article abstract of DOI:10.1590/S0103-50532011000300014

Derivatives of 3,4-dihydropyrimidin-2-(1H)-ones were synthesized in excellent yields in short reaction time by one pot, three component reaction of aldehydes, ethyl acetoacetate and urea (or thiourea) in room temperature ionic liquids (RTILs) under ultras

Full text of DOI:10.1590/S0103-50532011000300014

J. Braz. Chem. Soc., Vol. 22, No. 3, 511-516, 2011.
Printed in Brazil - ©2011 Sociedade Brasileira de Química
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Article
A
A Convenient and Efficient Protocol for the One Pot Synthesis of
3,4-Dihydropyrimidin-2-(1H)-ones Catalyzed by Ionic Liquids
under Ultrasound Irradiation
Abhishek N. Dadhania, Vaibhav K. Patel and Dipak K. Raval*
Department of Chemistry, Sardar Patel University, Vallabh Vidyanagar, 388 120, Gujarat, India
Derivados de 3,4-dihidropirimidin-2-(1H)-onas foram sintetizados via uma reação one-pot
de três componentes, com excelentes rendimentos em curtos tempos reacionais, usando aldeídos,
acetoacetato de etila e uréia (ou tiouréia) em líquidos iônicos à temperatura ambiente (RTILs) sob
radiação de ultrassom, sem adição de catalisador. Um mecanismo sintético plausível foi postulado
levando em consideração o papel catalítico dos líquidos iônicos em promover a reação. Os líquidos
iônicos puderam ser reciclados no mínimo seis vezes com boa retenção de atividade.
Derivatives of 3,4-dihydropyrimidin-2-(1H)-ones were synthesized in excellent yields in short
reaction time by one pot, three component reaction of aldehydes, ethyl acetoacetate and urea (or
thiourea) in room temperature ionic liquids (RTILs) under ultrasound irradiation without any
added catalyst. A plausible mechanistic pathway has been postulated based on the catalytic role
of the ionic liquid in promoting the reaction. The ionic liquids could be recycled at least six times
with retention of their activity.
Keywords: one pot synthesis, 3,4-dihydropyrimidin-2-(1H)-ones, ionic liquid, ultrasound
Introduction
acidic clay montmorillonite KSF, zeolites, FeCl3·6H2O,
LaCl3·7H2O, Yb(OTf)3, InCl3 have been reported. In
addition, microwave9 and ultrasound10 are also reported to
promote the Biginelli three component cyclocondensation
reaction. Most of the reported methods employ strong acidic
conditions, high temperature and require long reaction
times, or use expensive catalysts. From a literature survey,
emerged the need to carry out this reaction with higher atom
utilization and shorter reaction times under milder reaction
conditions.
Ionic liquids (ILs) have attracted extensive research
interest as environmental benign solvents due to their
negligible vapour pressure, solvating ability, reusability
and high thermal stability.11 Apart from this, some ILs
possess inherent Lewis/Bronsted acidity;12 by combining
these unique properties they have emerged as a ‘‘green
reaction media’’. The use of ILs as reactions media may
offer a convenient solution to both the solvent emission and
catalytic recycling problem with high efficiency.13 The use
of ultrasound is now well known to enhance the reaction
rates and yields of reactions under milder conditions.14
The considerable energy for transformation is liberated
by formation and collapse of bubbles. The reaction media
such as ILs, having negligible vapour pressure,15 should
change characteristics of cavitation and force less volatile
3,4-Dihydropyrimidin-2-(1H)-ones (DHPMs) and their
derivatives have attracted global interest because of their
pharmacological and therapeutic properties.1,2 They have
emerged as integral backbones of several calcium channel
blockers, antihypertensive agents, alpha-1a adrenergic
receptor antagonists.3 Several marine alkaloids containing
theDHPMunithaveshowninterestingbiologicalproperties.4
Synthetic strategies towards the dihydropyrimidine nucleus
involve one-pot to multistep approaches. The classical
synthesis of DHPM nucleus, condensation of ethyl
acetoacetate, benzaldehyde and urea under strong acidic
condition was low yielding (20-50%).1 Subsequent multistep
synthesis produced somewhat higher yields but lacked the
simplicity of one-pot, one-step procedure.5 Consequently,
for the synthesis of DHPMs many improved procedures
have been reported. Many of these procedures effectively
employed catalyst such as BF3·Et2O6 in combination
with transition metal salts and a proper proton source.
Polyphosphate ester7 was claimed to greatly improve the
yield. Recently, the use of various catalysts8 like polystyrene
sulphonic acid (PSSA), Bi(NO3)3, PhB(OH)2, TaBr5,
*e-mail: dipanalka@yahoo.com

512
A Convenient and Efficient Protocol for the One Pot Synthesis of DHPMs Catalyzed by Ionic Liquids
J. Braz. Chem. Soc.
substrates to undergo the cavitational activation. From
this fact, we planned for further innovations in this multi
component reaction (MCR) by practising sonochemistry
in ILs. Proceeding on the same lines, we opted to evolve
an efficient and ecofriendly process for the preparation
of ionic liquid 1-carboxymethyl-3-methylimidazolium
tetrafluoroborate [cmmim][BF4] by ultrasound irradiation.
Herein we disclose the preparation of [cmmim][BF4] via
ultrasound and report the synthesis of DHPMs promoted by
the combined use of ultrasound and the mixture of carboxy
functionalized ionic liquid [cmmim][BF4] and 1-butyl-
3-methylimidazolium tetrafluoroborate [bmim][BF4] at
30 oC in excellent isolated yields. The mixture of ILs can
be efficiently recovered and reused at least six times. The
process holds well without any added catalyst.
aco-solvent to increase thesolvationcapacityofthe medium.
With carboxyl-functionalized ionic liquid [cmmim][BF4] in
hand, various proportions with [bmim][BF4] were screened
for the model reaction to afford 5-ethoxycarbonyl-4-phenyl-
6-methyl-3,4-dihydropyrimidin-2-(1H)-one (Table 1).
When the voluminal ratio of [bmim][BF4] was increased
(entry 2, 3 and 4) a ramp in the yields with shorter reaction
time was observed. Based on that evidence the optimal ratio
of [cmmim][BF4] to [bmim][BF4] was chosen to be 2:1 (v/v).
Basedonthisinvestigation,anumberofDHPMs(Table2,a-o)
were successfully synthesized using the same proportion for
ILmixturefromvarietyofaldehydes.Thereactionproceeded
with low yield over a long reaction time when [bmim][BF4]
sole was employed as the reaction medium (Table 1,
entry 5). From this observation, it becomes evident that the
role of [bmim][BF4] is as a co-solvent, the reaction does
not get accelerated by its presence. A series of successful
experiments were run by using molecular solvents like
methanol and ethyl acetate as the co-solvents in lieu of
[bmim][BF4]. To avoid the use of molecular solvents, we
opted for [bmim][BF4] as the co-solvent for the reaction.
Results and Discussion
Song and co-workers16 have reported the synthesis
of [cmmim][BF4] under conventional conditions at
o
70 C. Herein we have successfully carried out the same
transformation under sonication at ambient temperature in
comparatively shorter duration.
Table 1. The effects of ratio between [cmmim][BF4] and [bmim][BF4] on
the synthesis of 2a under ultrasound irradiation
A variety of aldehydes were condensed with ethyl
acetoacetate and urea (or thiourea) as shown in Scheme 1.
Typical ultrasound assisted MCR of benzaldehyde, ethyl
acetoacetate and urea was chosen as a model reaction for
optimization.TheresultsareshowninTable1.Using[cmmim]
[BF4] as the sole solvent, the reaction system became non
homogeneous and proceeded with comparatively low yield
over a long reaction time, due to the low solvation capacity of
IL (entry 1). Consequently, another ionic liquid was added as
[cmmim][BF4]:
[bmim][BF4] (v/v)
time /
min
Yield /
(%)a
entry
1
2
3
4
5
1:0
3:1
2:1
1:1
0:1
60
55
40
50
60
83
90
96
92
81
aIsolated yield of 2a.
Table 2. Different DHPMs synthesized by Condensation of aldehydes 1a-o with EAA and urea-thiourea in ionic liquid under ultrasonic irradiation
Ultrasound irradiation
time / min
Yield /
(%)a
mp / °C
observed (lit.)b
Product 2
R
X
2a
2b
2c
2d
2e
2f
Ph–
4-O2N–C6H4–
4-F–C6H4–
O
O
O
O
O
O
O
O
O
O
O
O
S
40
65
55
45
40
45
40
35
45
50
45
45
50
55
70
96
97
94
94
95
97
94
96
94
96
94
92
91
94
91
201-202 (202-204)17
206-208 (207-209)18
174-176 (175-176)20
192-194 (193-195)17
214-215 (215-216)18
200-202 (202-204)17
208-210 (209-211)17
221-222 (222–224)17
228-230 (230-232)17
178-180 (180-182)19
202-203 (204-205)19
214-216 (215-217)17
207-208 (208-210)17
150-151 (150-152)17
201-203 (202-204)21
3-Cl–C6H4–
4-H3C–C6H4–
4-MeO–C6H4–
2-Furyl-
2g
2h
2i
2-Cl–C6H4–
4-HO–C6H4–
3,4,5-(MeO)3–C6H2–
4-HO,3-MeO–C6H3–
2-Thienyl
2j
2k
2l
2m
2n
2o
Ph–
4-MeO–C6H4–
3,4,5-(MeO)3–C6H2–
S
S
aYields after recrystallisation. bMelting points are uncorrected.

Vol. 22, No. 3, 2011
Dadhania et al.
513
O
R
O
X
O
H
30 oC, u.s.
30-70 min
NH2
BF4
O
O
O
H
N
EtO
Me
NH
N
O
Me
OEt
H2N
X = O, S
R
H
N
H
X
R = 1a-o
EAA
H
2a-o
O
O
O
O
O
BF4
BF4
H
H
H
H
N
N
H
N
N
Scheme 1. Synthesis of 3,4-dihydropyrimidin–2(1H)–ones.
O
O
O
O
O
All the reactions were monitored by TLC and carried
forward to maximum atom utilization. All the compounds
were characterized by melting point, IR, H NMR,
Scheme 2. Bonding of –COOH proton of [cmmim][BF4] with aldehydic
carbonyl oxygen of aldehyde and ketonic carbonyl oxygen of EAA.
1
13C NMR and mass spectral techniques. All the data were
in agreement with the cited literature. It was noticed that
the aldehydes having electron donating/withdrawing
substituent reacted in short reaction time to afford the
DHPMs in very good to excellent isolated yields.
From the experimental observations, it was noticed that
thereactionsdidnotproceedevenafterminutesofultrasound
irradiation in molecular solvents such as ethanol and ethyl
acetate in place of the ILs. Similarly, formation of DHPMs
was not observed when the reactions were conducted in
the ILs under simple stirring at 30 °C without ultrasonic
irradiation. Thus the combined use of ultrasound irradiation
and the ionic liquid as reaction medium has promoted
Biginelli reaction in absence of any added catalyst.
The IL [cmmim][BF4] promotes the reaction due to
its inherent Brønsted acidity. The -COOH proton of
[cmmim][BF4] is capable of bonding with the aldehydic
carbonyl oxygen of aldehyde as well as ketonic carbonyl
oxygen of ethylacetoacetate as shown in Scheme 2.
Evidence for this was obtained by recording 13C NMR
spectra of p-tolualdehyde (neat) and EAA (neat) with
an external lock of D2O. The results are shown in Table
3. When 13C NMR spectra of neat p-tolualdehyde and
EAA were recorded, the chemical shift for aldehydic and
ketonic carbonyl carbon was observed respectively at
190.6 and 200.4 ppm. When 13C NMR spectra of both the
substrates were recorded with one equivalent of [cmmim]
[BF4] under similar conditions, no significant change was
observed in the chemical shifts of carbonyl carbon (only
ca. 0.2 ppm), possibly due to the low solvation capacity
of the IL. However, when the 13C NMR spectra of both the
substrates when recorded in a 2:1 mixture of [cmmim][BF4]
and [bmim][BF4] under similar conditions, significant
change in the chemical shifts were observed for aldehydic
and ketonic carbonyl carbons (ca. 5 ppm) for both due to
their interaction with IL. A plausible mechanistic pathway
has been postulated based on this evidence (Scheme 3).
Table 3. 13C NMR chemical shifts for the formyl and ketonic carbonyl
carbons of p-tolualdehyde and EAA
Chemical Shifta,
entry
1
Substrate
d / ppm
O
190.6
H
O
2
3
+ [cmmim][BF4]
190.8
196.0
H
O
+ [cmmim][BF4]
+ [bmim][BF4]
H
O
O
O
O
O
O
4
5
6
200.4
200.7
OEt
OEt
OEt
+ [cmmim][BF4]
+ [cmmim][BF4]
+ [bmim][BF4]
205.10
aRecorded neat with D2O as external lock.
O
OH
O
O
OEt
N
–H2O
N
H
O
O
R
N
NH2
H2N
N
R
O
O
O
BF4
H
R
H
O
H
BF4
N
H
N
H2N
NH2
O
O
R
R
R
O
O
H
EtO
NH
NH
–H2O
NH
O
EtO
O
EtO
HN
N
H
O
N
H
O
HO
H
H
O
N
BF4
N
O
Scheme 3. Plausible mechanistic pathway for the reaction.

514
A Convenient and Efficient Protocol for the One Pot Synthesis of DHPMs Catalyzed by Ionic Liquids
J. Braz. Chem. Soc.
o
The activity of recycled ionic liquid was studied in
ultrasound at 70 C for 2.5 h. Water was removed from
the reaction mixture by subjecting it to evaporation for
4 h at 80 °C under reduced pressure (10 mm Hg) to give
the product [cmmim][BF4] as a slight yellowish oil. This
the synthesis of 2a. After product separation, the aqueous
filtrate was subjected to vacuum for 4h, to leave behind
the mixture of ionic liquids. This mixture was reused in
the next run without any further purification. As shown in
Figure 1 the reaction medium can be reused for at least six
times without significant decrease in the yields.
was characterized by H NMR and 13C NMR. All the
1
data were in good agreement with the reported method.
1H NMR (400 MHz, D2O): d 8.38 (s, 1H), 7.11-7.12 (d,
J 1.6 Hz, 2H), 4.73 (s, 2H), 3.55 (s, 3H).
General procedure for the synthesis of DHPMs
A mixture containing aldehyde 1 (10 mmol), ethyl
acetoacetate (EAA, 10 mmol) and urea or thiourea
(11 mmol) in the mixture of [cmmim][BF4] and
[bmim][BF4](2:1, 2 g) was exposed to ultrasound at 30 oC.
The reactions were carried out in a 25 mL capacity round
bottom flask. Reactant mixture was suspended at the center
of the bath, slight below the water surface.At completion of
the reaction (as indicated byTLC), a solid product gradually
formed was poured into crushed ice (20 g) and stirred for
15-20min.Thesolidseparatedwasfilteredthroughasintered
funnel under suction, washed with ice-cold water (15 mL)
and then recrystalliszed from hot ethanol or ethyl acetate to
afford pure DHPMs, 2a-o. The combined aqueous filtrate
was heated at 80 °C under reduced pressure (10 mm Hg)
for 4 h to leave behind the mixture of ILs in near complete
recovery, pure enough to recycle. The recovered ionic liquid
mixture was found to be equally effective for at least six
recycles in the synthesis of 2a.
Figure 1. Recyclability of ionic liquid mixture.
Experimental
Materials
All chemicals were of research grade and were used
as obtained. The reactions were performed in D-compact
ultrasonic cleaner with a frequency of 50 kHz and power
250 W. IR spectra were recorded on a FT IR Perkin Elmer
Spectrum GX spectrometer, mass spectra on a Shimadzu
GCMS QP 2010 instrument, elemental analysis on
Spectral data for some selected DHPMs
1
Perkin Elmer PE 2400 elemental analyzer and H NMR
5-Ethoxycarbonyl-6-methyl-4-phenyl-3,4-dihydro-
pyrimidin-2(1H)-one (2a)
and 13C NMR spectra were recorded on Bruker Avance
400 MHz spectrometer in CDCl3/DMSO-d6 with TMS as
an internal standard. The melting points are uncorrected and
are compared with the reported literature values.
IR (KBr) νmax/cm-1: 3233, 2954, 1730, 1690, 1206,
698; 1H NMR: d 9.21 (s, 1H), 7.74 (s, 1H), 7.25 (m, 5H),
5.14 (s, 1H), 3.98 (q, J 7.1 Hz, 2H), 2.25 (s, 3H), 1.09 (t,
13
J 7.1 Hz, 3H); C NMR: d 13.9, 17.7, 53.9, 59.1, 99.2,
Preparation of carboxyl-functionalized ionic liquid
[cmmim][BF4]
126.1, 127.1, 128.3, 144.7, 148.2, 152.0, 165.2. Calc. for
C14H16N2O3: C, 64.60; H, 6.20; N, 10.76. Found: C, 64.61;
H, 6.18; N, 10.74. MS: 261 (M+1).
Aliquots of chloroacetic acid (1 equiv.) was added
over a period of 60 min to 1-methyl-imidazole (1 equiv.)
at room temperature under stirring, and then the reaction
mixture was exposed to ultrasound for an additional
period of 120 min at ambient temperature. The solid
thus obtained was washed with acetonitrile, and dried
under vacuum. The intermediate, 1-carboxymethyl-3-
methylimidazolium chloride was obtained as a white
solid (mp 172-174 °C). The [cmmim][Cl] (1 equiv.) and
NaBF4 (1 equiv.) were dissolved in H2O and exposed to
5-Ethoxycarbonyl-6-methyl-4-(4-fluorophenyl)-3,4-
dihydropyrimidin-2(1H)-one (2c)
IR (KBr) νmax/cm-1: 3240, 2980, 1730, 1640, 1230,
1
1150, 790; H NMR: d 9.25 (s, 1H), 7.77 (s, 1H), 7.21
(m, 4H), 5.15 (s, 1H), 3.99 (q, J 7.1 Hz, 2H), 2.26 (s, 3H),
1.09 (t, J 7.1 Hz, 3H); 13C NMR: d 13.9, 17.8, 53.6, 59.5,
123.4, 127.5, 145.2, 149.3, 151.6, 152.1, 164.8. Calc. for
C14H15FN2O3: C, 60.42; H, 5.43; N, 10.07. Found: C, 60.44;
H, 5.42; N, 10.10.

Vol. 22, No. 3, 2011
Dadhania et al.
515
5-Ethoxycarbonyl-6-methyl-4-(4-methoxyphenyl)-3,4-
dihydropyrimidin-2(1H)-one (2f)
3. Baldwin, J. J.; Claremon, D. A.; McClure, D. E.; U.S. Patent 4
609 494, 1986; Baldwin, J. J.; Ptizenberger, S. M.; McClure,
D. E.; U.S. Patent 675 321, 1987; Atwal, K. S.; U.S. Patent
4 684 655, 1987; Atwal, K. S.; U.S. Patent 4 684 656, 1987;
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Morita, M.; Noguchi, T.; J. Med. Chem. 1989, 32, 2399; Atwal,
K. S.; Rovnyak, G. C.; Kimball, S. D.; Floyd, D. M.; Moreland,
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K. M.; Malley, M. F.; J. Med. Chem. 1990, 33, 2629; Atwal,
K. S.; Swanson, B. N.; Unger, S. E.; Floyd, D. M.; Moreland,
S.; Hedberg, A.; O’Reilly, B. C.; J. Med. Chem. 1991, 34, 806;
Nagarathnam, D.; Chiu, G.; Dhar, T.; Wong, W.; Marzabadi, M.;
Gluchowski, C.;Lagu, B.;Miao, S.; PCTInt.Appl.WO96/14846.
4. Overman, L. E.; Rabinowitz M. H.; Renhowe, P. A.; J. Am.
Chem. Soc. 1995, 117, 2657; Snider, B. B.; Shi, Z.; J. Org.
Chem. 1993, 58, 3828.
IR (KBr) νmax/cm-1: 3206, 2956, 1740, 1679, 1245,
1
1180, 1040, 875; H NMR: d 9.14 (s,1H), 7.66 (s, 1H),
6.99 (m, 4H), 5.07 (s, 1H), 3.96 (q, J 6.8 Hz, 2H), 3.70 (s,
3H), 2.23 (s, 3H), 1.09 (t, J 6.8 Hz, 3H); 13C NMR: d 14.5,
18.2, 53.78, 55.47, 59.60, 99.9, 114.1, 127.8, 136.4, 148.3,
158.8, 165.8. Calc. for C15H18N2O4: C, 62.06; H, 6.25;
N, 9.65. Found: C, 62.04; H, 6.28; N, 9.67. MS: 291 (M+1).
5-Ethoxycarbonyl-6-methyl-4-(3,4,5-trimethoxyphenyl)-
3,4-dihydropyrimidin-2(1H)-thione (2o)
IR (KBr) νmax/cm-1: 3284, 2967, 1720, 1632, 1234,
1
1140, 780; H NMR: d 10.21 (s,1H), 9.49 (s, 1H), 7.29
(m, 2H), 5.02 (s, 1H), 6.40 (s, 2H), 3.94 (q, J 6.6 Hz, 2H),
3.57 (s, 9H) 2.13 (s, 3H), 1.04 (t, J 7.0 Hz, 3H); 13C NMR:
d 14.9, 17.7, 54.2, 56.1, 60.1, 60.4, 101.2, 103.5, 137.1,
139.4, 145.7, 153.3, 165.4, 174.5. Calc. for C17H22N2O5S:
C, 55.72; H, 6.05; N, 7.64. Found: C, 55.69; H, 6.03; N, 7.62.
5. Atwal, K. S.; O’Reilly, B. C.; Gougoutas, J. Z.; Malley, M. F.;
Heterocycles 1987, 26, 1189; Atwal, K. S.; Rovnyak, G. C.;
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3454.
Conclusions
The synergistic effect of ILs and ultrasound has been
successfully demonstrated to offer an easy way for the
synthesis of DHPMs in excellent yields in a single pot
reaction. The milder conditions, absence of additional
catalyst, high reaction rates, excellent yields, easy work
up and combined use of ionic liquids and ultrasound make
this procedure an improved alternative to the conventional
acid/base catalyzed thermal processes and is environment
friendly with minimal or no waste.
7. Kappe, C. O.; Falsone, S. F.; Synlett 1998, 7, 718.
8. Polshettiwar, V.; Varma, R. S.; Tetrahedron Lett. 2007, 48,
7343; Banik, B. K.; Reddy, A. T.; Datta, A.; Mukhopadhyay,
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B.; Amimour, M.; Belfaitah, A.; Rhouati, S.; Carboni, B.;
Tetrahedron Lett. 2006, 47, 5697; Ahmed, N.; van Lier J. E.
Tetrahedron Lett. 2007, 48, 5407; Bigi, F.; Carloni, S.; Frullanti,
B.; Maggi, R.; Sartori, G.; Tetrahedron Lett. 1999, 40, 3465;
Radha Rani, V.; Srinivas, N.; Radha Krishnan, M.; Kulkarni, S.
J.; Raghavan, K. V.; Green Chem. 2001, 3, 305; Lu, J.; Ma, H.;
Synlett 2000, 1, 63; Lu, J.; Bai,Y.; Wang, Z.;Yang, B.; Ma, H.;
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A.; Jana, U.; J. Org. Chem. 2000, 65, 6270.
Supplementary Information
Spectral data for all synthesized DHPMs and13C NMR
spectra in evidence for bonding of IL with p-tolualdehyde are
available free of charge at http://jbcs.sbq.org.br, as PDF file.
Acknowledgments
Authors thank Dr. H. S. Patel (Sardar Patel University)
for providing infrastructural and other facilities and
Vaibhav Analytical Laboratory-Ahmadabad for IR
facilities. A. N. Dadhania also thanks University Grant
Commission, New Delhi for the award of Meritorious
Student Fellowship-2008.
9. Gupta, R.; Gupta, A. K.; Paul, S.; Kachroo, P. L.; Indian J.
Chem. B 1995, 34, 151; Kappe, C. O.; Kumar, D.;Varma, R. S.;
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E. J.; Ramalingam, T.; J. Chem. Res. (S) 2000, 354; Stefani,
H. A.; Gatti, P. M.; Synth. Commun. 2000, 30, 2165; Kidwai,
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2. Kappe, C. O.; Tetrahedron 1993, 49, 6937.

516
A Convenient and Efficient Protocol for the One Pot Synthesis of DHPMs Catalyzed by Ionic Liquids
J. Braz. Chem. Soc.
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Submitted: July 16, 2010
Published online: November 4, 2010

J. Braz. Chem. Soc., Vol. 22, No. 3, S1-S3, 2011.
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Supplementary Information
SI
A Convenient and Efficient Protocol for the One Pot Synthesis of
3,4-Dihydropyrimidin-2-(1H)-ones Catalyzed by Ionic Liquids
under Ultrasound Irradiation
Abhishek N. Dadhania, Vaibhav K. Patel and Dipak K. Raval*
Department of Chemistry, Sardar Patel University, Vallabh Vidyanagar, 388 120, Gujarat, India
Spectral data for all synthesized DHPMs
5-Ethoxycarbonyl-6-methyl-4-(2-furyl)-3,4-dihydro-
pyrimidin-2(1H)-one (2g)
5-Ethoxycarbonyl-6-methyl-4-(4-nitrophenyl)-3,4-
dihydropyrimidin-2(1H)-one (2b)
IR (KBr) νmax/cm-1: 3234, 2918, 1727, 1648, 1234,
1
1113; H NMR: d 9.24 (s,1H), 7.75 (s, 1H), 7.54 (s, 1H),
IR (KBr) νmax/cm-1: 3224, 2950, 1745, 1670, 1510,
6.34 (s, 1H), 6.08 (s, 1H), 5.19 (s, 1H), 4.01 (q, J 6.9 Hz,
2H), 2.22 (s, 3H), 1.12 (t, J 6.9 Hz, 3H); 13C NMR: d 14.1,
17.7, 47.8, 59.1, 96.8, 105.2, 110.3, 142.3, 149.2, 152.2,
155.9, 165.2. Calc. for C12H14N2O4: C, 57.59; H, 5.64;
N, 11.19. Found: C, 57.55; H, 5.62; N, 11.21.
1
1340, 1125, 780; H NMR: d 9.37 (s,1H), 8.20 (d, 2H),
7.91 (s, 1H), 7.50 (d, 2H), 5.27 (s, 1H), 3.98 (q, J 7.1
Hz, 2H), 2.27 (s, 3H), 1.09 (t, J 7.1 Hz, 3H); 13C NMR: d
13.9, 17.8, 53.6, 59.3, 123.7, 127.5, 146.6, 149.3, 151.7,
151.9, 164.9. Calc. for C14H15N3O5: C, 55.08; H, 4.95; N,
13.76. Found: C, 55.05; H, 4.97; N, 13.74.
5-Ethoxycarbonyl-6-methyl-4-(2-chlorophenyl)-3,4-
dihydropyrimidin-2(1H)-one (2h)
5-Ethoxycarbonyl-6-methyl-4-(3-chlorophenyl)-3,4-
dihydropyrimidin-2(1H)-one (2d)
IR (KBr) νmax/cm-1: 3109, 2948, 1725, 1698, 1177, 1089,
750; 1H NMR: d 9.25 (s,1H), 7.70 (s, 1H), 7.33 (m, 4H),
5.61 (s, 1H), 3.87 (q, J 6.9 Hz, 2H), 2.28 (s, 3H), 0.98 (t,
J6.9Hz, 3H);13CNMR:d13.9, 17.7, 51.6, 59.1, 98.2, 127.7,
128.8, 129.1, 129.4, 131.8, 141.7, 149.2, 151.4, 165.0. Calc.
for C14H15ClN2O3: C, 57.05; H, 5.13; N, 9.50. Found:
C, 57.08; H, 5.15; N, 9.53.
IR (KBr) νmax/cm-1: 3254, 2966, 1738, 1669, 1170, 1096,
759; 1H NMR: d 9.24 (s,1H), 7.77 (s, 1H), 7.26 (m, 4H),
5.14 (s, 1H), 3.98 (q, J 7.1 Hz, 2H), 2.25 (s, 3H), 1.09 (t,
J7.1Hz, 3H);13CNMR:d14.0, 17.8, 53.6, 59.3, 98.7, 124.9,
126.2, 127.2, 130.4, 132.9, 147.2, 148.9, 151.9, 165.2. Calc.
for C14H15ClN2O3: C, 57.05; H, 5.13; N, 9.50. Found:
C, 57.08; H, 5.16; N, 9.48.
5-Ethoxycarbonyl-6-methyl-4-(4-hydroxyphenyl)-3,4-
dihydropyrimidin-2(1H)-one (2i)
5-Ethoxycarbonyl-6-methyl-4-(4-methylphenyl)-3,4-
dihydropyrimidin-2(1H)-one (2e)
IR (KBr) νmax/cm-1: 3358, 3219, 2930, 1731, 1678, 1171,
1
819; H NMR: d 9.34 (s,1H), 9.10 (s, 1H), 7.64 (s, 1H),
IR (KBr) νmax/cm-1: 3260, 2980, 1720, 1635, 1248, 1120,
6.84 (m, 4H), 5.02 (s, 1H), 3.96 (q, J 7.0 Hz, 2H), 2.21 (s,
3H), 1.08 (t, J 7.0 Hz, 3H); 13C NMR: d 13.7, 17.45, 54.4,
59.2, 101.1, 115.0, 127.7, 133.8, 146.9, 153.0, 156.8, 165.4.
Calc. for C14H16N2O4: C, 60.86; H, 5.84; N, 10.14. Found:
C, 60.84; H, 5.86; N, 10.16.
1
775; H NMR: d 9.15 (s,1H), 7.80 (s, 1H), 7.10 (s, 4H),
5.09 (s, 1H), 3.96 (q, J 7.1 Hz, 2H), 2.23 (s, 3H), 1.08 (t,
J 7.1 Hz, 3H); 13C NMR: d 14.1, 17.7, 20.6, 53.7, 59.1, 99.4,
126.1, 128.8, 136.3, 141.7, 148.2, 152.2, 165.2. Calc. for
C15H18N2O3: C, 65.68; H, 6.61; N, 10.21. Found: C, 65.64;
H, 6.59; N, 10.23.
5-Ethoxycarbonyl-6-methyl-4-(3,4,5-trimethoxyphenyl)-
3,4-dihydropyrimidin-2(1H)-one (2j)
IR (KBr) νmax/cm-1: 3215, 2922, 1732, 1676, 1248, 1126,
1
821; H NMR: d 9.23 (s,1H), 7.75 (s, 1H), 6.53 (s, 2H),
*e-mail: dipanalka@yahoo.com

2
A Convenient and Efficient Protocol for One Pot Synthesis
J. Braz. Chem. Soc.
5.13 (s, 1H), 4.02 (q, J 6.6 Hz, 2H), 3.72 (s, 9H), 2.25 (s,
3H), 1.13 (t, J 7.0 Hz, 3H); 13C NMR: d 14.2, 17.8, 54.1,
56.0, 59.4, 60.1, 99.3, 104.3, 140.6, 148.5, 152.5, 152.9,
165.4. Calc. for C17H22N2O6: C, 58.28; H, 6.33; N, 8.00.
Found: C, 58.24; H, 6.30; N, 8.03.
59.3, 99.8, 124.1, 124.9, 126.3, 148.7, 148.9, 152.3, 165.0.
Calc. for C12H14N2O3S: C, 54.12; H, 5.30; N, 10.52. Found:
C, 54.15; H, 5.34; N, 10.54.
5-Ethoxycarbonyl-6-methyl-4-phenyl-3,4-dihydro-
pyrimidin-2(1H)-thione (2m)
5-Ethoxycarbonyl-6-methyl-4-(4-hydroxy-3-methoxy-
phenyl)-3,4-dihydropyrimidin-2(1H)-one (2k)
IR (KBr) νmax/cm-1: 3200, 2956, 1720, 1678, 1180, 1097,
694;1H NMR: d 10.32 (s,1H), 9.64 (s, 1H), 7.27 (m, 5H),
5.15 (d, 1H), 4.01 (q, J 7.0 Hz, 2H), 2.27 (s, 3H), 1.09 (t,
J 7.0 Hz, 3H); 13C NMR: d 14.4, 17.6, 54.4, 60.0, 101.1,
126.8, 128.1, 129.2, 140.4, 143.9, 153.7, 165.5. Calc. for
C14H16N2O2S: C, 60.85; H, 5.84; N, 10.14. Found: C, 60.84;
H, 5.80; N, 10.16.
IR (KBr) νmax/cm-1: 3384, 3238, 2994, 1726, 1642, 1210,
1140, 756; 1H NMR: d 9.35 (s,1H), 9.10 (s, 1H), 7.68 (s,
1H), 7.32 (m,3H), 6.10 (s, 1H), 4.12 (q, J 7.2 Hz, 2H), 3.45
(s, 3H), 2.32 (s, 3H), 1.10 (t, J 7.2 Hz, 3H); 13C NMR: d
13.6, 18.8, 54.4, 61.7, 101.7, 113.54, 127.8, 128.9, 139.6,
141.8, 146.4, 148.3, 158.8, 165.8. Calc. for C15H18N2O5:
C, 58.82; H, 5.92; N, 9.15. Found: C, 58.79; H, 5.93; N,
9.12.
5-Ethoxycarbonyl-6-methyl-4-(4-methoxyphenyl)-3,4-
dihydropyrimidin-2(1H)-thione (2n)
IR (KBr) νmax/cm-1: 3088, 2933, 1730, 1687, 1247, 1175,
944; 1H NMR: d 10.28 (s,1H), 9.59 (s, 1H), 7.01 (m, 4H),
5.10 (s, 1H), 3.98 (q, J 7.0 Hz, 2H), 3.70 (s, 3H), 2.27 (s,
3H), 1.09 (t, J 7.0 Hz, 3H); 13C NMR: d 14.1, 17.6, 53.9,
55.2, 59.6, 101.2, 113.7, 127.5, 135.3, 144.7, 158.2, 165.2,
174.2. Calc. for C15H18N2O3S: C, 58.80; H, 5.92; N, 9.14.
Found: C, 58.78; H, 5.95; N, 9.11.
5-Ethoxycarbonyl-6-methyl-4-(2-thienyl)-3,4-dihydro-
pyrimidin-2(1H)-one (2l)
IR (KBr) νmax/cm-1: 3228, 2954, 1734, 1664, 1242, 1127,
786; 1H NMR: d 9.31 (s,1H), 7.88 (s, 1H), 7.35 (d, 1H),
6.90 (m, 2H), 5.39 (s, 1H), 4.05 (q, J 7.1 Hz, 2H), 2.20 (s,
3H), 1.15 (t, J 7.1 Hz, 3H); 13C NMR: d 14.2, 17.7, 49.9,
Copies of 13C NMR spectra in evidence for bonding of IL with p-tolualdehyde
Figure S1. 13C NMR spectrum of neat p-tolualdehyde.

Vol. 22, No. 3, 2011
Dadhania et al.
3
Figure S2. 13C NMR spectrum of p-tolualdehyde + [cmmim][BF4].
Figure S3. 13C NMR spectrum of p-tolualdehyde + [cmmim][BF4] + [bmim][BF4].