Ionic liquid-catalyzed one-pot synthesis of 1 H-pyrano[2,3-d[pyrimidin-2(8a H)-one derivatives via three-component reaction under solvent-free conditions

Article abstract of DOI:10.1080/00397911.2011.574246

A series of 1H-pyrano[2,3-d]pyrimidin-2(8aH)-one derivatives were synthesized via one-pot, three-component reaction of aromatic aldehydes, urea or thiourea, and 3,4-dihydro-2H-pyran using the green and inexpensive Brnsted acidic ionic liquid 1-methyl-2-py

Full text of DOI:10.1080/00397911.2011.574246

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Ionic Liquid–Catalyzed One-Pot Synthesis
of 1H-Pyrano[2,3-d]pyrimidin-2(8aH)-
one Derivatives via Three-Component
Reaction under Solvent-Free Conditions
Hong-Yun Guo a , Xiao-Jun Li a & Yi Yu a
a College of Chemical Engineering and Materials, Zhejiang University
of Technology, Zhejiang, China
Accepted author version posted online: 10 Jan 2012.Published
online: 21 Jun 2012.
To cite this article: Hong-Yun Guo , Xiao-Jun Li & Yi Yu (2012): Ionic Liquid–Catalyzed One-Pot
Synthesis of 1H-Pyrano[2,3-d]pyrimidin-2(8aH)-one Derivatives via Three-Component Reaction
under Solvent-Free Conditions, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 42:20, 3011-3020
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Synthetic Communications1, 42: 3011–3020, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.574246
IONIC LIQUID–CATALYZED ONE-POT SYNTHESIS OF
1H-PYRANO[2,3-d]PYRIMIDIN-2(8aH)-ONE
DERIVATIVES VIA THREE-COMPONENT REACTION
UNDER SOLVENT-FREE CONDITIONS
Hong-Yun Guo, Xiao-Jun Li, and Yi Yu
College of Chemical Engineering and Materials, Zhejiang University of
Technology, Zhejiang, China
GRAPHICAL ABSTRACT
Abstract A series of 1H-pyrano[2,3-d]pyrimidin-2(8aH)-one derivatives were synthesized
via one-pot, three-component reaction of aromatic aldehydes, urea or thiourea, and 3,4-
dihydro-2H-pyran using the green and inexpensive Brønsted acidic ionic liquid 1-methyl-2-
pyrrolidinone hydrosulfate ([Hnmp]HSO4) as catalyst under solvent-free conditions. The
method has several advantages such as mild conditions, shorter reaction time, good yields,
and environmentally benign procedure. Moreover, the catalyst could be recovered con-
veniently and reused at least four times without evident loss of activity.
Keywords Ionic liquid; 1H-pyrano[2,3-d]pyrimidin-2(8aH)-one derivatives; solvent-free;
three-component reaction
INTRODUCTION
Multicomponent reactions (MCRs) have received a great deal of attention,
most notably for the construction of heterocyclic libraries.[1,2] MCR strategies offer
significant advantages of convergence, productivity, ease of execution, generally
good yields of products, and reduced number of synthetic steps. The first MCRs
were described by Strecker in 1850 for the synthesis of amino acids,[3] and in the past
decades, there has been tremendous development in three-component reactions and
great efforts to afford new and effective MCRs.[4–6] Meanwhile, in recent times, the
Received December 11, 2010.
Address correspondence to Hong-Yun Guo, College of Chemical Engineering and Materials,
Zhejiang University of Technology, Zhejiang, China. E-mail: guohy63@163.com
3011

3012
H.-Y. GUO, X.-J. LI, AND Y. YU
Scheme 1. Synthesis of 1H-pyrano[2,3-d]pyrimidin-2(8aH)-one derivatives.
use of room-temperature ionic liquids[7] as excellent alternatives in organic synthetic
processes has gained considerable importance because of their solvating ability,
negligible vapor pressure, easy recyclability, and reusability. Many reactions, for
instance, Friedel–Crafts alkylation,[8] hydrogenation,[9] Heck reaction,[10] Suzuki
coupling reaction,[11] Biginelli reaction,[12] Beckmann rearrangement reaction,[13]
and Pechmann reaction[14] could react in the room-temperature ionic liquids.
1H-Pyrano[2,3-d]pyrimidin-2(8aH)-one derivatives, a novel class of pyranopyr-
imidiones, and related fused-ring pyrimidiones both possess various important
bioactivities, such as antitumor, antihypertensive, vasodilator, hepatoprotective,
cardiotonic, and antiallergic activities. Some also exhibit antimalarial, antifungal,
analgesics, anti-HIV, and herbicidal properties.[15–17]
To the best of our knowledge, only a few methods are available for the prep-
aration of 1H-pyrano[2,3-d]pyrimidin-2(8aH)-one derivatives;[18–20] however, these
methods have various drawbacks: reactions require a long time, toxic organic sol-
vent, and expensive catalyst. Therefore, it is desirable to develop a more efficient
and general method for the synthesis of 1H-pyrano[2,3-d] pyrimidin-2(8aH)-one
derivatives.
In this regard, our own interest had focused on the development of novel meth-
ods for the preparetion of various 1H-pyrano[2,3-d]pyrimidin-2(8aH)-one deriva-
tives using ionic liquid as catalyst under solvent-free conditions. Here we report
the results of our investigation that enabled an alternative preparation of 1H-
pyrano[2,3-d]pyrimidin-2(8aH)-one derivatives (4) from aromatic aldehydes (1), urea
or thiourea (2), and 3,4-dihydro-2H-pyran (3) in the presence of acidic ionic liquid
[Hnmp]HSO4 as catalyst at 110 ꢀC under solvent-free conditions (Scheme 1).
RESULTS AND DISCUSSION
Initially, the three-component reaction of 4-fluorophenyl aldehyde (1a,
1 mmol), urea (2, 1 mmol), and 3,4-dihydro-2H-pyran (3, 1 mmol) was carried out
in different solvents in the presence of [Hnmp]HSO4. Table 1 shows that the solvent-
free condition resulted in the most yield and shortest reaction time. Therefore, we
chose solvent-free conditions for all further reactions. It is environmentally friendly,
the toxic reagents can be avoided, and better yields are obained.
To further optimize the reaction temperature, the same three reagents were
allowed to react at temperatures ranging from 70 to 130 ꢀC under solvent-free con-
ditions, with an increment of 10 ꢀC each time. The results are shown in Table 2. The

IONIC LIQUID–CATALYZED THREE-COMPONENT REACTION
3013
Table 1. Solvent optimization for the synthesis of 4aa
Entry
Solvent
Temperature (ꢀC)
Time (h)
Yield (%)b
1
2
3
4
5
6
—
H2O
110
1=12
24
92
0
Reflux
Reflux
Reflux
Reflux
Reflux
CH3OH
EtOH
CH3CN
CHCl3
10
10
15
23
30
29
10
10
aAll reactions were run with 4-fluorophenyl aldehyde (1a, 1 mmol), urea (2, 1 mmol),
3,4-dihydro-2H-pyran (3, 1 mmol), and 10 mol % [Hnmp]HSO4.
bIsolated yield.
yield of product 4a was increased, and the reaction time was shortened as the tem-
perature increased from 70 to 110 ꢀC (Table 2, entries 1–5). However, further
increase of the temperature from 110 to 130 ꢀC failed to improve the yield of product
4a (Table 2, entries 6 and 7). Therefore, 110 ꢀC was chosen as the reaction tempera-
ture for all further reactions under solvent-free conditions.
It can be seen from Table 3 that the reaction conditions for the three-
component reaction gave the anticipated 1H-pyrano[2,3-d]pyrimidin-2(8aH)-one
derivatives in excellent yields and aromatic aldehydes carrying either electron-
donating or electron-withdrawing substituents reacted very well in good to excellent
yields. We also found that the aromatic aldehydes with electron-withdrawing groups
had better reactivity (shorter reaction time and better yields) than those bearing
electron-donating groups, so it was concluded that the electronic nature of the sub-
stituents on aldehydes had some effect on those reactions. In this study, all the pro-
ducts were characterized by melting point (mp), infrared (IR), 1H NMR, and
elemental analyses.
The ionic liquid plays an important role in the MCR system. Therefore, we also
studied the reuse of [Hnmp]HSO4. Just 10 mol % ionic liquid was sufficient to push
the reaction forward. More amounts of the ionic liquid did not improve the results
to a great extent. It also should be noted that [Hnmp]HSO4 as catalyst could be
Table 2. Temperature optimization for the synthesis of 4aa
Entry
Temperature (ꢀC)
Time (min)
Yield (%)b
1
2
3
4
5
6
7
70
80
60
60
30
20
5
71
75
81
90
92
85
79
90
100
110
120
130
10
10
aAll reactions were run with 4-fluorophenyl aldehyde (1a, 1 mmol), urea (2, 1 mmol),
3,4-dihydro-2H-pyran (3, 1 mmol), and 10 mol% [Hnmp]HSO4 under solvent-free
conditions.
bIsolated yield.

3014
H.-Y. GUO, X.-J. LI, AND Y. YU
Table 3. Multicomponent reactions of aromatic aldehydes, urea or thiourea, and 3,4-dihydro-2H-pyran
for the synthesis of 4a–4n
Entry
R
X
Product
Time (min)
Yield (%)a
1
2
4-FC6H4
O
O
O
O
O
O
O
S
4a
4b
4c
4d
4e
4f
5
5
92
94
90
90
93
88
86
90
89
88
87
90
84
82
4-ClC6H4
3-BrC6H4
C6H5
3
10
10
5
4
5
4-NO2C6H4
4-CH3C6H4
4-CH3OC6H4
4-FC6H4
6
20
30
20
20
20
10
10
35
35
7
4g
4h
4i
8
9
4-ClC6H4
3-BrC6H4
C6H5
S
10
11
12
13
14
S
4j
S
4k
4l
4-NO2C6H4
4-CH3C6H4
4-CH3OC6H4
S
S
4m
4n
S
aIsolated yield.
Table 4. Studies on the reuse of [Hnmp]HSO4 in the
preparation of 4a
Round
Yield (%)a
1
2
3
4
5
92
90
91
89
80
aIsolated yield.
Scheme 2. Possible mechanism for the synthesis of 1H-pyrano[2,3-d]pyrimidin-2(8aH)-one derivatives.

IONIC LIQUID–CATALYZED THREE-COMPONENT REACTION
3015
recovered easily and reused several times without any decrease in terms of efficiency
in the reaction. The corresponding product still could be obtained in good yield
when [Hnmp]HSO4 was reused in the fourth round as shown in Table 4.
Finally, a possible mechanism for the formation of 1H-pyrano[2,3-d]-
pyrimidin-2(8aH)-one derivatives is proposed in Scheme 2. It involves the initial for-
mation of the N-acyliminium ion intermediate (5) from an aldehyde and urea in the
presence of ionic liquid. Then 5 undergoes complex formation with 3,4-dihydro-(2-
H)-pyran (3) and generates an oxonium ion intermediate (6). Then the product 4
arises from the trapping of intermediate 6.
CONCLUSION
In summary, a series of 1H-pyrano[2,3-d]pyrimidin-2(8aH)-one derivatives
were synthesized using the green and inexpensive ionic liquid [Hnmp]HSO4 as
catalyst under solvent-free conditions. The procedure offered several advantages
including greater yields, operational simplicity, cleaner reactions, and minimal
environmental impact and provided a useful and attractive protocol for the synthesis
of those compounds.
EXPERIMENTAL
Melting points were determined with a X-4 microscopic melting-point appar-
atus and were uncorrected. IR spectra were recorded on a Nexus 670 spectrometer
1
in KBr. H NMR spectra was measured on a Bruker Avance-II 500-MHz spec-
trometer using tetramethylsilane (TMS) as internal standard and dimethylsulfoxide
(DMSO-d6) as solvent. Elemental analyses were performed on a Flash EA 1112
elemental analyzer.
The synthesis of this task-specific ionic liquid had been carried out from a simi-
lar method in the literature.[21] The ionic liquid was formed quantitatively and in
1
high purity as assessed by H NMR. All other chemicals (analytical-regent grade)
were commercially available and used without further purification.
Synthesis of 1H-Pyrano[2,3-d]pyrimidin-2(8aH)-one Derivatives 4
The mixture of the aromatic aldehyde (1, 1 mmol), urea (2, 1 mmol), and 3,4-
dihydro-2H-pyran (3, 1 mmol) were added to a 20-mL round-bottom flask contain-
ing 10 mol % [Hnmp]HSO4, after being stirred for appropriate time at 110 ꢀC
(monitored by thin-layer chromatography TLC). Upon completion, the mixture
was added with 5 mL EtOH. The precipitate was collected by suction and purified
by recrystallization from EtOH to give the desired product, and the results are listed
in Table 3. Then the filtrate was concentrated under the reduced pressure and dried to
recover the ionic liquid for subsequent use.
4-(4-Fluorophenyl)-hexahydro-1H-pyrano[2,3-d]pyrimidin-2(8aH)-
one (4a)
This compound was obtained as a white powder with mp 232–234 ꢀC IR
1
(KBr): 3291, 3074, 2937, 2865, 1669, 1604, 1509, 1419 cmꢁ1; H NMR (DMSO-d6,

3016
H.-Y. GUO, X.-J. LI, AND Y. YU
500 MHz): d 7.22–7.16 (m, 5H), 6.92 (s, 1H), 4.58 (d, J ¼ 11.0 Hz, 1H), 4.38 (q,
J ¼ 2.0 Hz, 1H), 3.84 (t, J ¼ 7.0 Hz, 1H), 3.43 (q, J ¼ 8.5 Hz, 1H), 1.57–1.31 (m,
3H), 1.24 (d, J ¼ 10.0 Hz, 2H); MS (EI) m=z 251 ([M þ H]þ). Anal. calcd. for
C13H15FN2O2: C, 62.39; H, 6.04; N, 11.19. Found: C, 62.37; H, 6.05; N, 11.17.
4-(4-Chlorophenyl)-hexahydro-1H-pyrano[2,3-d]pyrimidin-2(8aH)-
one (4b)
This compound was obtained as a white powder with mp 248–250 ꢀC; IR
1
(KBr): 3305, 3096, 2943, 2864, 1681, 1669, 1596, 1409 cmꢁ1; H NMR (DMSO-d6,
500 MHz): d 7.21–7.11 (m, 5H), 6.47 (s, 1H), 4.49 (d, J ¼ 11.0 Hz, 1H), 4.41 (d,
J ¼ 2.0 Hz, 1H), 3.88 (d, J ¼ 7.0 Hz, 1H), 3.42 (t, J ¼ 11.5 Hz, 1H), 1.69–1.42 (m,
2H), 1.31–1.29 (m, 1H), 1.23–1.19 (m, 2H); MS (EI) m=z 267 ([M þ H]þ). Anal.
calcd. for C13H15ClN2O2: C, 58.54; H, 5.67; N, 10.50. Found: C, 58.59; H, 5.59;
N, 10.47.
4-(3-Bromophenyl)-hexahydro-1H-pyrano[2,3-d]pyrimidin-2(8aH)-
one (4c)
This compound was obtained as a white powder with mp 246–248 ꢀC; IR
1
(KBr): 3229, 3090, 2937, 2858, 1688, 1668, 1497, 1428 cmꢁ1; H NMR (DMSO-d6,
500 MHz): d 7.50 (t, J ¼ 7.5 Hz, 2H), 7.37–7.28 (m, 3H), 6.67 (s, 1H), 4.54 (d,
J ¼ 6.0 Hz, 1H), 4.43–4.42 (q, J ¼ 2.5 Hz, 1H), 3.88 (d, J ¼ 7.5 Hz, 1H), 3.48–3.43
(m, 1H), 1.85–1.82 (m, 2H), 1.61–1.55 (m, 1H), 1.26 (t, J ¼ 9.0 Hz, 2H); MS (EI)
m=z 311 ([M þ H]þ). Anal. calcd. for C13H15BrN2O2: C, 50.18; H, 4.86; N, 9.00.
Found: C, 50.16; H, 4.88; N, 9.01.
4-Phenyl-hexahydro-1H-pyrano[2,3-d]pyrimidin-2(8aH)-one (4d)
This compound was obtained as white powder with mp 220–222 ꢀC; IR (KBr):
;
3261, 2964, 2912, 2367, 1688, 1667, 1504, 1439 cmꢁ1 1H NMR (DMSO-d6,
500 MHz): d 7.34–7.27 (m, 6H), 6.56 (s, 1H), 4.52 (d, J ¼ 10.5 Hz, 1H), 4.40 (s,
1H), 3.88 (d, J ¼ 9.5 Hz, 1H), 3.42 (t, J ¼ 10.0 Hz, 1H), 1.78–1.67 (m, 2H),
1.54–1.49 (m, 1H), 1.23–1.17 (m, 2H); MS (EI) m=z 233 ([M þ H]þ). Anal. calcd.
for C13H16N2O2: C, 67.22; H, 6.94; N, 12.06. Found: C, 67.26; H, 6.95; N, 12.00.
4-(4-Nitrophenyl)-hexahydro-1H-pyrano[2,3-d]pyrimidin-2(8aH)-one
(4e)
This compound was obtained as yellow powder with mp 237–239 ꢀC; IR (KBr):
;
3307, 3215, 3098, 2940, 2860, 1698, 1519, 1493 cmꢁ1 1H NMR (DMSO-d6,
500 MHz): d 8.23 (d, J ¼ 8.5 Hz, 2H), 7.65 (d, J ¼ 8.5 Hz, 2H), 7.36 (d, J ¼ 2.5 Hz,
1H), 6.81(s, 1H), 4.72 (d, J ¼ 10.5 Hz, 1H), 4.45 (t, J ¼ 2.0 Hz, 1H), 3.90 (d,
J ¼ 8.0 Hz, 1H), 3.45 (m, 1H), 1.87–1.79 (m, 2H), 1.62–1.23 (m, 3H); MS (EI) m=z
278 ([M þ H]þ). Anal. calcd. for C13H15N3O4: C, 56.31; H, 5.45; N, 15.15. Found:
C, 56.25; H, 5.48; N, 15.16.

IONIC LIQUID–CATALYZED THREE-COMPONENT REACTION
3017
4-p-Tolyl-hexahydro-1H-pyrano[2,3-d]pyrimidin-2(8aH)-one (4f)
This compound was obtained as white powder with mp 244–246 ꢀC; IR (KBr):
3275, 2939, 2861, 1687, 1509, 1441 cmꢁ1 1H NMR (DMSO-d6, 500 MHz): d
;
7.22–7.16 (m, 5H), 6.47 (s, 1H), 4.49 (d, J ¼ 11.0 Hz, 1H), 4.41(q, J ¼ 2.0 Hz, 1H),
3.88 (t, J ¼ 7.0 Hz, 1H), 3.42 (m, 1H), 2.30 (s, 3H), 1.68–1.06 (m, 5H); MS (EI)
m=z 247 ([M þ H]þ). Anal. calcd. for C14H18N2O2: C, 68.27; H, 7.37; N, 11.37.
Found: C, 68.23; H, 7.41; N, 11.40.
4-(4-Methoxyphenyl)-hexahydro-1H-pyrano[2,3-d]pyrimidin-2(8aH)-
one (4g)
This compound was obtained as white powder with mp 232–234 ꢀC; IR (KBr):
1
3264, 1681, 1615, 1498, 1270, 1255, 1173 cmꢁ1; H NMR (DMSO-d6, 500 MHz): d
7.25 (s, 1H), 7.20 (d, J ¼ 7.5 Hz, 2H), 6.92 (d, J ¼ 8.0 Hz, 2H), 6.74 (s, 1H), 4.45
(d, J ¼ 10.5 Hz, 1H), 4.39 (m, 1H), 3.86 (d, J ¼ 11.5 Hz, 1H), 3.75 (s, 3H), 3.43 (t,
J ¼ 10.5 Hz, 1H), 1.57–1.83 (m, 5H); MS (EI) m=z 263 ([M þ H]þ). Anal. calcd.
for C14H18N2O3: C, 64.10; H, 6.92; N, 10.68. Found: C, 64.06; H, 6.93; N, 10.69.
4-(4-Fluorophenyl)-hexahydro-1H-pyrano[2,3-d]pyrimidin-2(8aH)-
thione (4h)
This compound was obtained as white powder with mp 245–247 ꢀC; IR (KBr):
1
3175, 2975, 2860, 1574, 1538, 1508, 1442 cmꢁ1; H NMR (DMSO-d6, 500 MHz): d
8.67 (d, J ¼ 2.5 Hz, 1H), 8.31 (s, 1H), 7.21–7.17 (m, 2H), 7.14–7.04 (m, 2H), 4.34
(d, J ¼ 9.5 Hz, 1H), 4.21 (s, 1H), 3.65 (d, J ¼ 11.0 Hz, 1H), 3.32 (t, J ¼ 10.5 Hz,
1H), 1.68–1.34 (m, 3H), 1.08 (d, J ¼ 9.5 Hz, 2H); MS (EI) m=z 267 ([M þ H]þ). Anal.
calcd. for C13H15FN2OS: C, 58.63; H, 5.68; N, 10.52. Found: C, 58.60; H, 5.72; N,
10.47.
4-(4-Chlorophenyl)-hexahydro-1H-pyrano[2,3-d]pyrimidin-2(8aH)-
thione (4i)
This compound was obtained as white powder with mp 245–247 ꢀC; IR (KBr):
1
3186, 2976, 2836, 1572, 1535, 1491, 1438 cmꢁ1; H NMR (DMSO-d6, 500 MHz): d
8.85 (d, J ¼ 3.0 Hz, 1H), 8.46 (s, 1H), 7.43 (d, J ¼ 8.5 Hz, 2H), 7.34 (d, J ¼ 8.5 Hz,
2H), 4.52 (d, J ¼ 10.5 Hz, 1H), 4.39 (m, 1H), 3.86 (d, J ¼ 11.5 Hz, 1H), 3.45 (m,
1H), 1.85 (t, J ¼ 5.0 Hz, 1H), 1.75–1.70 (m, 1H), 1.65–1.60 (m, 1H), 1.22 (d,
J ¼ 8.0 Hz, 2H); MS (EI) m=z 283 ([M þ H]þ). Anal. calcd. for C13H15ClN2OS: C,
55.21; H, 5.35; N, 9.91. Found: C, 55.20; H, 5.37; N, 9.89.
4-(3-Bromophenyl)-hexahydro-1H-pyrano[2,3-d]pyrimidin-2(8aH)-
thione (4j)
This compound was obtained as white powder with mp 260–262 ꢀC; IR (KBr):
;
3388, 3227, 3060, 2927, 2848, 1556, 1514, 1416 cmꢁ1 1H NMR (DMSO-d6,
500 MHz): d 8.87 (d, J ¼ 3.0 Hz, 1H), 8.51(s, 1H), 7.52 (d, J ¼ 4.5 Hz, 2H), 7.33 (d,

3018
H.-Y. GUO, X.-J. LI, AND Y. YU
J ¼ 6.0 Hz, 2H), 4.52 (d, J ¼ 10.5 Hz, 1H), 4.40-4.39 (m, 1H), 3.86 (d, J ¼ 11.5 Hz,
1H), 3.50–3.46 (m, 1H), 1.91 (t, J ¼ 4.0 Hz, 1H), 1.78–1.73 (m, 1H), 1.67–1.61 (m,
1H), 1.26–1.24 (t, J ¼ 3.0 Hz, 2H); MS (EI) m=z 327 ([M þ H]þ). Anal. calcd. for
C13H15BrN2OS: C, 47.71; H, 4.62; N, 8.56. Found: C, 47.70; H, 4.64; N, 8.58.
4-Phenyl-hexahydro-1H-pyrano[2,3-d]pyrimidin-2(8aH)-thione (4k)
This compound was obtained as white powder with mp 245–247ꢀC; IR (KBr):
1
3170, 2970, 2848, 1572, 1534, 1451, 1373 cmꢁ1; H NMR (DMSO-d6, 500 MHz): d
8.80 (d, J ¼ 2.0 Hz, 1H), 8.36 (s, 1H), 7.41 (d, J ¼ 7.5 Hz, 2H), 7.34 (m, 2H), 7.19
(m, 2H), 4.48 (d, J ¼ 4.0 Hz, 1H), 4.39 (t, J ¼ 3.0 Hz, 1H), 3.42 (t, J ¼ 10.0 Hz,
1H), 1.87–1.85(m, 1H), 1.75–1.60 (m, 2H), 1.19 (d, J ¼ 10.0 Hz 2H); MS (EI) m=z
249 ([M þ H]þ). Anal. calcd. for C13H16N2OS: C, 62.87; H, 6.49; N, 11.28. Found:
C, 62.86; H, 6.37; N, 11.29.
4-(4-Nitrophenyl)-hexahydro-1H-pyrano[2,3-d]pyrimidin-2(8aH)-
thione (4l)
This compound was obtained as yellow powder with mp 257–259 ꢀC; IR (KBr):
1
3282, 3178, 3070, 2949, 2862, 1604, 1564, 1520, 1444 cmꢁ1; H NMR (DMSO-d6,
500 MHz): d 8.94 (d, J ¼ 3.0 Hz, 1H), 8.63 (s, 1H), 8.24 (d, J ¼ 8.5 Hz, 2H), 7.61
(d, J ¼ 9.0 Hz, 2H), 4.69 (d, J ¼ 10.5 Hz, 1H), 4.42–4.41 (m, 1H), 3.87 (d, J ¼ 6.5 Hz,
1H), 3.51–3.47 (m, 1H), 1.92 (t, J ¼ 4.0 Hz, 1H), 1.76 (t, J ¼ 11.5 Hz, 1H), 1.68–1.62
(m, 1H), 1.28–1.20 (m, 2H); MS (EI) m=z 294 ([M þ H]þ). Anal. calcd. for
C13H15N3O3S: C, 53.23; H, 5.15; N, 14.32. Found: C, 53.10; H, 5.18; N, 14.37.
4-p-Tolyl-hexahydro-1H-pyrano[2,3-d]pyrimidin-2(8aH)-thione (4m)
This compound was obtained as white powder with mp 254–256 ꢀC; IR (KBr):
3196, 2973, 2902, 2842, 1571, 1458 cmꢁ1; 1H NMR (DMSO-d6, 500 MHz): d 8.64 (s,
1H), 8.23 (s, 1H), 7.12 (m, 4H), 4.31(d, J ¼ 9.5 Hz, 1H), 4.21 (s, 1H), 3.65 (d,
J ¼ 11.0 Hz, 1H), 3.32 (t, J ¼ 10.5 Hz, 1H), 2.13 (s, 3H), 1.78–1.56 (m, 4H), 1.15
(d, J ¼ 7.0 Hz, 1H); MS (EI) m=z 263 ([M þ H]þ). Anal. calcd. for C14H18N2OS:
C, 64.09; H, 6.91; N, 10.68. Found: C, 64.01; H, 6.94; N, 10.64.
4-(4-Methoxyphenyl)-hexahydro-1H-pyrano[2,3-d]pyrimidin-2(8aH)-
thione (4n)
This compound was obtained as white powder with mp 263–265 ꢀC; IR (KBr):
;
3185, 2974, 2944, 2869, 1614, 1569, 1514, 1461 cmꢁ1 1H NMR (DMSO-d6,
500 MHz): d 8.79 (d, J ¼ 2.5 Hz, 1H), 8.29 (s, 1H), 7.22 (d, J ¼ 9.0 Hz, 2H), 6.92
(d, J ¼ 9.0 Hz, 2H), 4.45 (d, J ¼ 10.5 Hz, 1H), 4.40–4.38 (m, 1H), 3.86 (d, J ¼ 11.5 Hz,
1H), 3.76 (s, 3H), 3.49–3.44 (m, 1H), 1.83 (t, J ¼ 5.0 Hz, 1H), 1.68 (t, J ¼ 12.0 Hz, 1H),
1.64–1.57 (m, 1H), 1.26–1.22 (m, 2H); MS (EI) m=z 279 ([M þ H]þ). Anal. calcd. for
C14H18N2OS: C, 60.41; H, 6.52; N, 10.06. Found: C, 60.38; H, 6.54; N, 10.02.

IONIC LIQUID–CATALYZED THREE-COMPONENT REACTION
3019
ACKNOWLEDGMENT
This work was financially supported by the Research Foundation of Zhejiang
Provincial Education Department (No. 20060811).
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