Lanthanide triflate catalyzed one-pot synthesis of dihydropyrimidin-2(1H)-thiones by a three-component of 1,3-dicarbonyl compounds, aldehydes, and thiourea using a solvent-free Biginelli condensation

Article abstract of DOI:10.1081/SCC-120018755

Novel one-pot Biginelli-type reaction has been developed. Aromatic and aliphatic aldehydes with β-dicarbonyl compounds and thiourea in the presence of catalytic amount 5 mol % of Yb(OTf)3 at 100° C for 60-90min under solvent-free conditions proceeded smoo

Full text of DOI:10.1081/SCC-120018755

This article was downloaded by: [Universita degli Studi di Torino]
On: 01 July 2013, At: 06:24
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,
37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
Lanthanide Triflate Catalyzed One-Pot Synthesis of
Dihydropyrimidin-2(1H)-thiones by a Three-Component
of 1,3-Dicarbonyl Compounds, Aldehydes, and
Thiourea Using a Solvent-Free Biginelli Condensation
Limin Wang a , Changtao Qian b , He Tian a & Yun Ma c
a Institute of Fine Chemicals, East China University of Science and Technology, Shanghai, P.R.
China
b Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, Shanghai, P.R. China
c Department of Chemistry, Cornell University, Ithaca, New York, USA
Published online: 16 Aug 2006.
To cite this article: Limin Wang , Changtao Qian , He Tian & Yun Ma (2003): Lanthanide Triflate Catalyzed One-Pot Synthesis
of Dihydropyrimidin-2(1H)-thiones by a Three-Component of 1,3-Dicarbonyl Compounds, Aldehydes, and Thiourea Using
a Solvent-Free Biginelli Condensation, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 33:9, 1459-1468
To link to this article: http://dx.doi.org/10.1081/SCC-120018755
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to
anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation that the contents
will be complete or accurate or up to date. The accuracy of any instructions, formulae, and drug doses should
be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims,
proceedings, demand, or costs or damages whatsoever or howsoever caused arising directly or indirectly in
connection with or arising out of the use of this material.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 9, pp. 1459–1468, 2003
Lanthanide Triflate Catalyzed One-Pot Synthesis
of Dihydropyrimidin-2(1H )-thiones by a
Three-Component of 1,3-Dicarbonyl Compounds,
Aldehydes, and Thiourea Using a Solvent-Free
Biginelli Condensation
2
1
3
Limin Wang,1, Changtao Qian, He Tian, and Yun Ma
*
1Institute of Fine Chemicals, East China University of
Science and Technology, Shanghai, P.R. China
2Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of
Sciences, Shanghai, P.R. China
3Department of Chemistry, Cornell University,
Ithaca, New York, USA
ABSTRACT
Novel one-pot Biginelli-type reaction has been developed. Aromatic
and aliphatic aldehydes with b-dicarbonyl compounds and thiourea
*Correspondence: Limin Wang, Institute of Fine Chemicals, East China
University of Science and Technology, 130 Meilong Lu, Shanghai 200237,
P.R. China; Fax: 86-21-64252288; E-mail: wanglimin@ecust.edu.cn.
1459
DOI: 10.1081/SCC-120018755
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
1460
Wang et al.
in the presence of catalytic amount 5 mol% of Yb(OTf )3 at100 ꢀ C
for 60–90 min under solvent-free conditions proceeded smoothly
to afford corresponding dihydropyrimidin-thiones. The yields
of the classical Biginelli reaction can be increased from 20–50%
to 81–91% while the reaction time was shortened from 18–48 h to
60–90 min. In addition the catalyst can be easily recovered and
reused.
Key Words: Lanthanide triflate; Biginelli reaction; One-pot synth-
esis; Dihydropyrimidin-2(1H)-thiones.
INTRODUCTION
In the recent years, the synthesis of Dihydropyrimidinones has
received an increasing amount of attention because their derivatives are
pharmacologically important as calcium channel blockers, antihyper-
tensive agents, and alpha1-1-a-antagonists.[1] Furthermore, several
marine alkaloids with interesting biological activities containing the
dihydropyrimidin-5-carboxylate unit have been isolated.[2] Thus,
synthetic methods for preparing this heterocyclic nucleus have been
developed.[3] In 1893 pietro Biginelli firstly reported the synthesis of
3,4-dihydropyrimidin-2(1H )-ones by a very simple one-potcondensation
reaction of benzaldehyde, ethyl acetoacetate, and urea under strongly
acidic conditions,[4] unfortunately, one serious drawback of this
Biginelli reaction is low yields (20–50%), when using substituted
aromatic, aliphatic aldehydes, in particular using thioureas.[5] Thus,
Biginelli reaction for the synthesis of DHPMs (‘‘Bignelli: Compounds,’’
DHPMs) has received renewed interest and several improved procedures
have recently been reported,[6] either by modification of the classical
[7]
one-potBiginelli approach istelf
or by the development of novel, but
more complex multi-step strategies[8] was reported that these methods
involve strong Lewis acids such as BF3,[9] Protic acids such as HCl[10]
and other milder Lewis acid such as InCl3,[11] BiCl3,[12] Ferric and Nickel
Chloride hexahydrates,[13] the acid clay montmorillonite KSF,[14]
Zeolite,[15] solid-supported ytterbium(III) reagent.[16] The reported
Biginell’s reactions normally require prolonged reaction time and using
organic solvent.
The use of lanthanide compounds, especially lanthanide triflates
Lewis acid as catalysts in organic synthesis has attracted great interest
from many chemists.[17] We have recently reported a series of lanthanide
triflates Lewis acid catalyzed organic reaction, such as ytterbium

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
Lanthanide Triflate Catalyzed Synthesis of Dihydropyrimidinones
1461
catalyzed ee reaction,[18] scandium triflate catalyzed [2 þ 2] cycloaddition
reaction,[19] one-pot synthesis of amino phosponate,[20] asymmetric
glyoxylate-ene reaction catalyzed by C2-symmtric chiral bis(oxazoline)-
lanthanide triflates complexes.[21]
Continuing our recent work in lanthanide triflate catalyzed
Biginelli reaction: one-pot synthesis of dihydropyrimidin under the
solvent-free condition,[22] we have focused our attention on the lan-
thanide triflate catalyzed synthesis of the dihydropyrimidin-2(1H )-
thiones. We wish to report here a novel lanthanide triflate catalyzed
Biginelli reaction, applied to one-pot synthesis of dihydropyrimidin-
2(1H )-thiones by a three component of thiourea, 1,3-dicarbonyl
compounds, aldehyde under solvent-free condition to, which not only
is very simple and excellent-yielding (81–91%) but also greatly
development environmentally friendly and effective synthetic methods.
RESULTS AND DISCUSSION
For the present study we have selected benzaldehyde, ethyl aceto-
acetate, and thiourea as model compounds using lanthanide triflate as a
catalyst and have tested a variety of reaction conditions (Sch. 1). It was
found that, in the presence of 0.05 equiv. of a lanthanide triflate, the
modification one-pot reaction of the classical Biginelli under
solvent-free can proceed smoothly to afford the corresponding dihydro-
pyrimidin-2(1H )-thiones in excellent yields. The reaction results are sum-
marized in Table 1. We investigated the effectiveness of three lanthanide
triflate, Yb(OTf )3, La(OTf )3, and La(OTf )3 in catalyzing the reaction
and compared with the reaction using several Lewis acids. There was no
significant difference among the three lanthanide triflates in terms of the
Scheme 1.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
1462
Wang et al.
Table 1. Reaction of benzaldehyde, ethyl acetoacetate, and thioureas under
different reaction conditions.
Amountof catalyst
(mol%)
Yield
(%)d
Entry
Solventa
Catalyst
1
2
H2O
Yb(OTf )3
Yb(OTf )3
Yb(OTf )3
Yb(OTf )3
Yb(OTf )3
Yb(OTf )3
Yb(OTf )3
Yb(OTf )3
Yb(OTf )3
Yb(OTf )3
Sc(OTf )3
La(OTf )3
LaCl3
5
5
18
80
Toluene
HOCH2CH2OCH3
CH2Cl2
THF
Noneb
None
None
3
5
85
16
4
5
5
5
34
92
6
5
7
20
10
2.5
1.5
5
91
91
8
9
None
None
88
78
10
11
12
13
14
15
16
17
18
None
None
89
86
5
None
None
5
40
43
ScCl3
YbCl3
5
None
None
5
46
ZnCl2
SnCl2
Yb(OTf )3
5
5
6
None
None
5
c
5
89, 87, 84
aRefluxed for 6 h; b100ꢀC for 60 min; cCatalyst was reused in three times;
dIsolated yield.
yield, butYb(OTf ) showed particularly superior catalytic activity and
3
could be reused three times and exhibited the same catalytic activity (the
yields of 4a: first: 89%, second: 87%, third: 84%). Use of just 5 mol% of
Yb(OTf )3 is sufficient to push the reaction forward. Higher amount of
Yb(OTf )3 did not improve the result to a great extent. Some lanthanide
compounds such as YbCl3, ScCl3, and LaCl3 gave low yields (46%, 43%,
and 40%) at the first use. In contrast, the other Lewis acids such as ZnCl2
and SnCl2 gave lower yields. Effectof solvents on the yields of dihydro-
pyrimidin-2(1H )-thiones in the model reaction under the influence of
a catalyst amount of Yb(OTf ) (5 mol%) are shown in Table 1 too.
HOCH2CH2OCH3 was the best solvent among those tested, such as
toluene (80%), THF (34%), Dichloromethane (16%), and water (18%).
Reaction under solvent-free condition is especially appealing, the yields
were significantly raised (92%), and the reaction time was shortened
from 18 h to 60 min.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
Lanthanide Triflate Catalyzed Synthesis of Dihydropyrimidinones
1463
The reaction of several aromatic and aliphatic aldehydes, 1,3-dicar-
bonyl compounds and thiourea were examined in the presence of a
catalytic amount (5 mol%) of Yb(OTf )3 under solvent-free at 100ꢀC
for 60 min (Sch. 2) and the results are summarized in Table 2. In all
cases, the one-pot reaction proceeded smoothly to afford the correspond-
ing dihydropyrimidin-2(1H )-thiones in high yield. Aromatic aldehydes
either electron-donating or electron-withdrawing provided excellent
yields of products, and aliphatic aldehydes such as n-valeric and is butyric
aldehyde afforded corresponding dihydropyrimidin products in 76% (4j)
and 75% (4i) yield. Aromatic aldehydes have higher reactivity than
aliphatic aldehydes. Similarly, an a,b-unsaturated aldehyde also give
Scheme 2.
Table 2. Ytterbium triflate catalyzed synthesis of different
dihydropyrimidinones under the solventless conditions.
Entry
R
R1
R2
ProductYield (%)
1
2
C6H5
C2H5O
C2H5O
C2H5O
C2H5O
C2H5O
C2H5O
C2H5O
C2H5O
C2H5O
C2H5O
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
4a
4b
4c
4d
4e
4f
92
90
88
89
87
86
81
80
75
76
85
91
4-(CH3O)-C6H4
4-(NO2)-C6H4
4-(Cl)-C6H4
2,4-(Cl)2-C6H3
3-(NO2)-C6H4
C6H5CH¼CH
C6H5CH2CH2
i-Pr
3
4
5
6
7
4g
4h
4i
8
9
10
11
12
n-Bu
C6H5
C6H5
4j
4k
4l
CH3O

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
1464
Wang et al.
the product 4g (81% yield). Compared to classical Biginelli method, one
additional important feature of the present protocol is the ability to
tolerate the variation in all the three components. Besides b-ketone
ester, the b-diketone can also be employed.
We have recently investigated the mechanism[22] of the Biginelli reac-
tion and proposed that it must first form an acyl imine intermediate, by
the reaction of the aldehyde with thiourea and activated by lanthanide
coordination which is the key and rate-limiting step, especially the S¼C
double bond by lanthanide is stabilized. Interception of the acyl imine by
b-ketoester compound produces an open chain ureide, which subse-
quently cyclizes to that dihydropyrimidin-2(1H )-thiones.
In conclusion, ytterbium triflate Yb(OTf )3 were found to be efficient
catalyst in one-pot reaction of aldehydes, 1,3-dicarbonyl compounds, and
thiourea to afford dihydropyrimidin-2(1H )-thiones in good for excellent
yields under solvent-free condition. This report discloses a new and simple
modification of the Biginelli’s reaction. The yields of the one-pot Biginelli
reaction can be increased from 20–50 to 81–91% while the reaction time
was shortened from 18–48 h to 60–90 min. Other important feature of this
Biginelli reaction is that the catalyst can be easily recovered from aqueous
layer after the reaction is completed and can be reused with no less of
yield. It not only led to economical automation, but also reduces hazar-
dous pollution to achieve environmentally friendly processes and could
replace traditional Lewis acid catalysis.
EXPERIMENTAL SECTION
General
1
Melting points were determined on a Kofler hot stage. H NMR
spectra were recorded at 300 MHz or 400 MHz in DMSO-d6 using
TMS as internal standard. 13C NMR spectral measurements were per-
formed at75 MHz using DMSO- d6 as an internal standard. IR spectra
were obtained as KBr plates on FTS-185. Mass spectra were determined
on a Finigan 8230 mass spectrometer.
Lanthanide triflate catalyzed synthesis of different dihydropyrimidin-
2(1H )-thione under the solventless conditions: aldehyde (1 mmol),
b-dicarbonyl compound (1 mmol), thiourea (1.5 mmol), and Yb(OTf )3
(0.05 mmol, 5 mol%) were heated at 100ꢀC, under stirring for
60–90 min. Then water was added and the product was extracted with
ethyl acetate. After the organic layer was dried (Na2SO4) and

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
Lanthanide Triflate Catalyzed Synthesis of Dihydropyrimidinones
1465
evaporated, the residue was recrystallized by ethyl acetate and hexane to
products 4.
5-Ethoxycarbonyl-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-thione
(4a): M.p. 207–208ꢀC; 1H NMR: ꢀ ¼ 10.30 (s, 1H, NH), 9.63 (s, 1H, NH),
7.28 (m, 5H, arom CH), 5.18 (s, 1H, CH), 4.00 (q, J ¼ 7.0 Hz, 2H, OCH2),
2.29 (s, 3H, CH3), 1.10 (t, J ¼ 7.06Hz, 3H, OCH2CH3); 13C NMR:
ꢀ ¼ 12.2, 15.5, 52.2, 57.8, 99.2, 124.7, 125.8, 126.6, 143.1, 163.4, 172.6; IR
(KBr): 3243, 1711, 1627cmꢁ1; MS (70 eV, EI): m/z (%): 276 (M, 60), 199
(100); Anal. calcd. for C14H16N2O2S: C, 60.85; H, 5.84; N, 10.14. Found:
C, 60.81; H, 5.85; N, 10.11.
5-Ethoxycarbonyl-4-(4-methoxyphenyl)-6-methyl-3,4-dihydropyrimidin-
2(1H )-thione (4b): M.p. 140–141ꢀC; H NMR: ꢀ ¼ 10.35 (s, 1H, NH),
1
9.57 (s, 1H, NH), 7.13 (d, J ¼ 8.65 Hz, 2H, arom CH), 6.90
(d, J ¼ 8.71 Hz, 2H, arom CH), 5.12 (s, 1H, CH), 4.00 (q, J ¼ 7.07 Hz,
2H, OCH2), 3.72 (s, 3H, OCH3), 2.29 (s, 3H, CH3), 1.11 (t, J ¼ 7.08 Hz,
3H, CH3); 13C NMR: ꢀ ¼ 14.0, 17.9, 55.1, 55.3, 60.2, 103.0, 114.0,
127.9, 134.7, 142.7, 159.4, 165.3, 173.7; IR (KBr): 3244, 1707,
1634 cmꢁ1; MS (70 eV, EI): m/z (%): 306 (M, 48), 277 (100); Anal.
calcd. for C15H18N2O3S: C, 58.80; H, 5.92; N, 9.14. Found:
C, 58.78; H, 5.82; N, 9.04.
5-Ethoxycarbonyl-6-methyl-4-(4-nitrophenyl)-3,4-dihydropyrimidin-2-
(1H )-thione (4c): M.p. 208–209ꢀC; 1H NMR: ꢀ ¼ 10.50 (s, 1H, NH), 8.28
(d, J ¼ 8.78 Hz, 2H, arom CH), 9.78 (s, 1H, NH), 7.78 (d, J ¼ 8.70 Hz,
2H, arom CH), 5.38 (d, J ¼ 3.2 Hz, 1H, CH), 4.07 (q, J ¼ 7.6 Hz, 2H,
OCH2), 2.35 (s, 3H, CH3), 1.12 (t, J ¼ 7.5 Hz, 3H, CH3); IR (KBr):
3238, 2971, 1725, 1701, 1658, 1593 cmꢁ1
;
Anal. calcd. for
C14H15N3O4S: C, 52.33; H, 4.71; N, 13.08. Found: C, 52.22; H, 4.61;
N, 13.12.
4-(4-Chlorophenyl)-5-ethoxycarbonyl-6-methyl-3,4-dihydropyrimidin-
2(1H )-thione (4d): M.p. 209–210ꢀC; H NMR: ꢀ ¼ 10.58 (s, 1H, NH),
1
9.75 (s, 1H, NH), 7.45 (d, J ¼ 0.8 Hz, 2H, arom CH), 7.28 (d,
J ¼ 8.6 Hz, 2H, arom CH), 5.16 (s, 1H, CH), 4.02 (q, J ¼ 7.1 Hz, 2H,
OCH2), 2.27 (s, 3H, CH3), 1.12 (t, J ¼ 7.1 Hz, 3H, CH3); IR (KBr):
3242, 1705, 1638 cmꢁ1; Anal. calcd. for C14H15N2O2ClS: C, 54.10; H,
4.86; N, 9.01. Found: C, 54.08; H, 4.76; N, 9.03.
4-(2,4-Dichlorophenyl)-5-ethoxycarbonyl-6-methyl-3,4-dihydropyrimi-
din-2(1H )- thione (4e): M.p. 225–228ꢀC; 1H NMR: ꢀ ¼ 10.68 (s, 1H, NH),
9.16 (s, 1H, NH), 7.67 (s, 1H, arom CH), 7.43 (d, J ¼ 8.1 Hz, 1H, arom CH),
7.34 (d, J ¼ 8.2 Hz, 1H, arom CH ), 5.63 (s, 1H, CH), 3.96 (q, J ¼ 7.3 Hz,
2H, OCH2), 2.30 (s, 3H, CH3), 1.01 (t, J ¼ 7.5 Hz, 3H, CH3); IR (KBr):
3359, 1695, 1624 cmꢁ1; Anal. calcd. for C14H14N2O2Cl2S: C, 48.71; H,
4.09; N, 8.11. Found: C, 48.69; H, 4.05; N, 8.08.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
1466
Wang et al.
5-Ethoxycarbonyl-6-methyl-4-(3-nitrophenyl)-3,4-dihydropyrimidin-2-
(1H )-thione (4f ): M.p. 206–207ꢀC; 1H NMR: ꢀ ¼ 10.56 (s, 1H, NH), 9.80
(s, 1H, NH), 8.08 (s, 1H, arom CH), 7.65–7.73 (m, 2H, arom CH), 5.36
(s, 1H, CH), 4.04 (q, J ¼ 7.6 Hz, 2H, OCH2), 2.34 (s, 3H, CH3), 1.11
(t, J ¼ 7.5 Hz, 3H, CH3); IR (KBr): 3170, 1715, 1661, 1593, 1540 cmꢁ1
;
Anal. calcd. for C14H15N3O4S: C, 52.33; H, 4.71; N, 13.08. Found:
C, 52.34; H, 4.66; N, 13.15.
5-Ethoxycarbonyl-6-methyl-4-styryl-3,4-dihydropyrimidin-2(1H )-thione
(4g): M.p. 223–225ꢀC; H NMR: ꢀ ¼ 10.13 (s, 1H, NH), 9.46 (s,1H, NH),
1
7.31–7.56 (m, 5H, arom CH), 6.36 (d, J ¼ 15.7Hz, 1H, H–C¼CH), 6.28
(dd, J ¼ 15.9, 6.0 Hz, 1H, CH¼C–H), 4.74 (d, J ¼ 5.70Hz, 1H, CH), 4.08
(m, 2H, OCH2), 2.29 (s, 3H, CH3), 1.21 (t, J ¼ 7.1 Hz, 3H, CH3); IR (KBr):
3242, 1706, 1653cmꢁ1; Anal. calcd. for C16H18N2O2S: C, 63.55; H, 6.00;
N, 9.26; Found: C, 63.56; H, 6.05; N, 9.22.
5-Ethoxycarbonyl-6-methyl-4-(2-phenylethane)-3,4-dihydropyrimidin-
2(1H )-thione (4h): M.p. 167–169ꢀC; 1H NMR: ꢀ ¼ 10.22 (s, 1H, NH), 9.23
(s, 1H, NH), 7.06–7.33 (m, 5H, arom CH), 4.20 (m, 1H, CH), 4.01 (m, 2H,
OCH2), 1.71 (t, 3H, CH3), 2.20 (s, 3H, CH3), 1.85 (m, 4H, CH2CH2); IR
(KBr): 3245, 1700, 1635 cmꢁ1; Anal. calcd. for C16H20N2O2S: C, 63.13;
H,6.62; N, 9.20. Found: C, 63.11; H, 6.60; N, 9.18.
4-Isopropyl-5-ethoxycarbonyl-6-methyl-3,4-dihydropyrimidin-2(1H )-
thione (4i): M.p. 191–192ꢀC; 1H NMR: ꢀ ¼ 10.05 (s, 1H, NH), 9.21 (s, 1H,
NH), 4.04 (m, 2H, OCH2), 3.95 (t, J ¼ 3.5 Hz, 1H, CH), 2.18 (s, 3H,
CH3), 1.66 (m, 1H, CH), 1.18 (t, J ¼ 7.1 Hz, 3H, CH3), 0.85 (d,
J ¼ 6.9 Hz, 3H, CH3), 0.76 (d, J ¼ 6.8 Hz, 3H, CH3); IR (KBr): 3235,
3104, 1691, 1643 cmꢁ1; Anal. calcd. for C11H18N2O2S: C, 54.52; H,
7.49; N, 11.56. Found: C, 54.50; H, 7.46; N, 11.51.
4-Butyl-5-ethoxycarbonyl-6-methyl-3,4-dihydropyrimidin-2(1H )-thione
(4j): M.p. 185–187ꢀC; 1H NMR: ꢀ ¼ 10.10 (s, 1H, NH), 9.25 (s, 1H, NH),
4.05 (m, 2H, OCH2), 2.50 (s, 3H, CH3), 1.15–1.39 (m, 9H, (CH2)3CH3),
0.86 (t, J ¼ 6.5 Hz, 3H, CH3); IR (KBr): 3247, 1721, 1646 cmꢁ1; MS (70 eV,
EI): m/z (%): 256 (M, 4), 199 (100); Anal. calcd. for C12H20N2O2S: C,
56.22; H, 7.86; N, 10.93. Found: C, 56.20; H, 7.81; N, 10.90.
5-Aceto-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H )-thione (4k):
M.p. 220–221ꢀC; H NMR: ꢀ ¼ 10.16 (s, 1H, NH), 9.66 (s, 1H, NH),
1
7.21–7.35 (m, 5H, arom CH), 5.23 (d, J ¼ 2.2 Hz, 1H, CH), 2.23 (s, 3H,
CH3CO), 2.06 (s, 3H, CH3 ); IR (KBr): 3254, 1693, 1672 cmꢁ1; Anal.
calcd. for C13H14N2OS: C, 63.39; H, 5.73; N, 11.37. Found: C, 63.35; H,
5.71; N, 11.33.
5-Methoxycarbonyl-4-phenyl-6-methyl-3,4-dihydropyrimidin-2(1H)-thione
(4l): M.p. 201–202ꢀC; HNMR: ꢀ ¼ 10.15 (s, 1H, NH), 9.27 (d, J¼ 3.1 Hz,
1
1H, NH), 7.22–7.35 (m, 5H, arom CH), 5.16 (d, J¼ 2.6Hz, 1H, CH), 3.52

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
Lanthanide Triflate Catalyzed Synthesis of Dihydropyrimidinones
1467
(s, 3H, OCH3), 2.25 (s, 3H, CH3); IR (KBr): 3332, 1696, 1653 cmꢁ1; Anal.
calcd. for C13H14N2O2S: C, 59.52; H, 5.38; N, 10.68. Found: C, 59.50; H,
5.36; N, 10.65.
ACKNOWLEDGMENT
We thank the National Nature Science Foundation of China and the
Science Foundation of East China University of Science and Technology
for their financial support.
REFERENCES
1. Atwal, K.S.; Rovnyak, G.C.; O’Reilly, B.C.; Schwartz, J. J. Org.
Chem. 1989, 54, 5898; Kappe, C.O.; Fabian, W.M.F.; Semones,
M.A. Tetrahedron 1997, 53, 2803; Atwal, K.S.; Swanson, B.N.;
Unger, S.E.; Floyd, D.M.; Moreland, S.; Hedberg, A.; O’Reilly,
B.C. J. Med. Chem. 1991, 34804 and references therein.
2. Sinder, B.B.; Shi, Z. J. Org. Chem. 1993, 58, 3828; Dzwonczyk,
Grover, G.J.; McMullen, S.; Normadinam, D.M.; Sleph, C.S.;
Moreland, S.J. J. Cardiovasc. Pharmacol. 1995, 26, 289.
3. Kappe, C.O. Tetrahedron 1993, 49, 6937.
4. Biginelli, P. Gazz. Chim. Ital. 1893, 23, 360; Kappe, C.O. Molecules
1998, 3, 1.
5. Hu, E.H.; Sinder, D.R.; Dolling, U.-H. J. Org. Chem. 1998, 63,
3454; Atwal, K.S.; Rovnyak, G.C.; O’Reilly, B.C.; Gougoutas,
J.Z.; Malley, D. J. Heterocycles 1987, 26, 1189; O’Reilly, B.C.;
Atwal, K.S. Heterocycles 1987, 26, 1185; Studer, A.; Jeger, P.;
Wipf, P.; Curran, D.P. J. Org. Chem. 1997, 62, 2917; Studer, A.;
Hadida, S.; Ferrito, R.; Kim, S.-Y.; Eger, P.; Wipf, P.; Curran, D.P.
Science 1997, 275, 823.
6. Gupta, R.; Gupta, A.K.; Paul, S.; Kachroo, P.L. Indian J. Chem.
1995, 34B, 61; Lu, Bigi, F.; Carloni, S.; Frullanti, B.; Maggi, R.;
Sartori, G. Tetrahedron Lett. 1999, 40, 3465; Kappe, C.O.; Falsone,
F.S. Synlett 1998, 718.
7. Shutalev, A.D.; Kishko, E.A.; Sivova, N.; Kuznetsov, A.Y.
Molecules 1998, 3, 100.
8. Shutalev, A.D.; Kuksa, V.A. Khim. Geterotsikl. Soedin. 1997, 105.
9. Hu, E.H.; Sinder, D.R.; Dolling, U.H. J. Org. Chem. 1998, 63, 3454.
10. Lu, J.; Ma, H.R. Synlett 2000, 63.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
1468
Wang et al.
11. Ranu, B.C.; Hajra, A.; Jana, U.; J. Org. Chem. 2000, 65, 6270.
12. Ramalinga, K.; Vijayalakshmi, P.; Kaimal, T.N.B. Synlett 2001,
6, 863.
13. Lu, J.; Bai, Y. Synthesis 2002, 4, 466.
14. Bigi, F.; Carloni, S.; Frullanti, B.; Maggi, R.; Sartori, G.
Tetrahedron Lett. 1999, 40, 3465.
15. Radha Rani, V.; Srinivas, N.; Radha Kishan, M.; Kulkarni, S.J.;
Raghavan, K.V. Green Chemistry 2001, 3, 305.
16. Dondoni, A.; Massi, A. Tetrahedron Lett. 2001, 42, 7975.
17. Kobayashi, S. Synlett. 1994, 689; Molander, G.A. Chem. Rev. 1992,
92, 29; Kobayashi, S. Eur. J. Org. Chem. 1999, 64, 15.
18. Qian, C.; Huang, T. Tetrahedron Lett. 1997, 38, 6721.
19. Ma, Y.; Qian, C. Tetrahedron Lett. 2000, 41, 945.
20. Qian, C.; Huang, T. J. Org. Chem. 1998, 63, 4125.
21. Qian, C.; Wang, L. Tetrahedron: Asymmetry 2000, 11, 2347.
22. Ma, Y.; Qian, C.; Wang, L.M.; Yang, M. J. Org. Chem. 2000,
65, 3864.
Received in Japan April 9, 2002