Magnesium bromide and magnesium chloride hexahydrate catalyzed one-pot synthesis of dihydropyrimidines via biginelli reaction under solvent-free conditions

Article abstract of DOI:10.1002/jhet.980

Biologically important 12 new important 3,4-dihydropyrimidin-2-(1H)-ones (-thiones) were synthesized with in one-pot three-component Biginelli reaction from the corresponding aromatic aldehydes (5-methyl-2-thiophenecarboxaldehyde and 2-chloro-5-nitrobenza

Full text of DOI:10.1002/jhet.980

Month 2013
Magnesium Bromide and Magnesium Chloride Hexahydrate
Catalyzed One‐Pot Synthesis of Dihydropyrimidines via Biginelli
Reaction under Solvent‐Free Conditions
*
Şirin Gülten
Department of Chemistry, Faculty of Arts and Sciences, Çanakkale Onsekiz Mart University,
Çanakkale 17020, Turkey
*
E-mail: siringulten@hotmail.com
Received March 3, 2011
DOI 10.1002/jhet.980
Published online 00 Month 2013 in Wiley Online Library (wileyonlinelibrary.com).
Biologically important 12 new important 3,4‐dihydropyrimidin‐2‐(1H)‐ones (‐thiones) were synthesized
with in one‐pot three‐component Biginelli reaction from the corresponding aromatic aldehydes (5‐methyl‐
2‐thiophenecarboxaldehyde and 2‐chloro‐5‐nitrobenzaldehyde), β‐keto esters (ethylacetoacetate, allylacetoacetate,
and t‐butylacetoacetate), and urea/thiourea in the presence of catalytic amount of magnesium bromide
and magnesium chloride hexahydrate as nontoxic, inexpensive, and easily available catalysts under
solvent‐free conditions at 80 and 100°C. Compared with the catalyst‐free three‐component Biginelli reaction
conditions, this method consistently has the advantage of short reaction time (45–100 min) and good to excellent
yields (75–91%).
J. Heterocyclic Chem., 00, 00 (2013).
INTRODUCTION
yields of products because of the side reaction, in particular,
when substituted aromatic aldehydes or thioureas are used.
Recently, many improved synthetic procedures using
different types of catalysts and conditions were reported for
the synthesis of DHPMs either by the modification of
classical Biginelli condensation or by the development of
novel but more complex multistage strategies [36–63].
However, despite their potential utility, some of these
procedures require expensive reagents, strong acidic conditions,
prolonged reaction time, high temperature, stoichiometric
amounts of catalyst, toxic reagents, large amount of solvents,
unsatisfactory yields, and inconvenient purification techniques.
Therefore, the discovery of a novel and inexpensive catalyst,
which can be easily separated and environmentally benign
procedure for the preparation of DHPMs under mild
conditions is of main importance. Recently, magnesium
bromide and magnesium chloride have had considerable
attention as a powerful reaction medium for effecting
various transformations [54–64]. Herein, we report an
efficient, economic, and practical route for the one‐pot
synthesis of DHPMs by Biginelli cyclocondensation
reaction using either magnesium bromide or magnesium
chloride hexahydrate as mild catalysts under solvent‐free
conditions (Scheme 1).
In recent years, 3,4‐dihydropyrimidin‐2‐(1H)‐ones
(DHPMs) and thiones have attracted significant attention
because of their wide range of biological activities such
as antihypertensives (calcium channel modulators), neuro-
peptide Y antagonists, antifungal, antibacterial, antiviral,
anticancer leads (mitotic kinesin Eg5 motor protein inhibi-
tors and blood platelet aggregation inhibitors), antioxidative,
anti‐inflammatory, antistaphylococcal antibiotics, and their
treating benign prostatic hyperplasia (α‐1a‐adrenergic recep-
tor antagonists) [1–28]. In addition, several isolated marine
alkaloids containing the 3,4‐dihydropyrimidinone‐5‐carbox-
ylate skeleton display interesting biological properties [29,
30]. Among them, the most notable are the batzelladine
alkaloids A and B which inhibit the binding of HIV envelope
protein gp‐120 to human CD4 cells which are potential
compounds in AIDS therapy [31–33]. Structurally simple
DHPM derivative Monastrol has emerged as a mitotic
kinesin Eg 5 motor protein inhibitor for the development of
anticancer drugs [34, 35]. Therefore, the synthesis of DHPM
core scaffold is of much current importance.
Classical Biginelli reaction suffers from the harsh reaction
conditions, lengthy reaction time and relatively low reaction
© 2013 HeteroCorporation

Ş. Gülten
Vol 000
Scheme 1. General procedure for the synthesis of DHPMs.
RESULTS AND DISCUSSION
We studied the Biginelli condensation using anhydrous
and hydrous salts as catalysts under solvent‐free conditions.
Inexpensive and easily available MgBr2 and MgCl2·6H2O
as catalysts were selected to the three‐component Biginelli
condensation under solvent‐free conditions. Twelve 4a‐l
variously substituted DHPMs were synthesized, and the
results obtained exhibited in Table 1.
Table 1
Magnesium bromide and magnesium chloride hexahydrate catalyzed one‐pot synthesis of DHPMs under solvent‐free conditions versus
catalyst‐free conditions.
Entries
R1
R2
X
O
Product
Time (min)
Yield (%)
Mp (found) (°C)/(lit.) (°C)
1
OEt
4a
45a 90b, 200c
88a, 85b, 55c
232–234/–
2
3
4
5
6
7
Ot‐Bu
OAllyl
OEt
O
O
S
4b
4c
4d
4e
4f
90a, 100b, 210c
45a, 100b, 210c
95a, 90b, 210c
60a, 90b, 220c
45a, 100b, 220c
60a, 90b, 130c
78a, 75b, 44c
85a, 82b, 50c
91a, 89b, 52c
77a, 75b, 43c
81a, 80b, 49c
91a, 88b, 58c
226–227/–
206–208/–
209–210/–
191–193/–
193–195/–
254–256/–
Ot‐Bu
OAllyl
OEt
S
S
O
4g
8
Ot‐Bu
OAllyl
OEt
O
O
S
4h
4i
45a, 60b, 130c
60a, 90b, 130c
80a, 90b, 160c
60a, 90b, 140c
90a, 120b, 150c
86a, 83b, 45c
86a, 82b, 47c
90a, 85b, 55c
85a, 81b, 44c
84a, 80b, 46c
238–239/–
215–217/–
193–195/–
208–210/–
158–160/–
9
10
11
12
4j
4k
4l
Ot‐Bu
OAllyl
S
S
The Biginelli reaction conditions:
aMethod I: MgBr2 (0.2 mmol), solvent‐free, 100°C.
bMethod II: MgCl2·6H2O (0.4 mmol), solvent‐free, 80°C.
cMethod III: catalyst‐free, EtOH (2 mL), 100°C.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
Magnesium Bromide and Magnesium Chloride Hexahydrate Catalyzed One-Pot Synthesis
of Dihydropyrimidines via Biginelli Reaction under Solvent-Free Conditions
Scheme 2. The plausible mechanism for MgBr2 and MgCl2·6H2O catalyzed Biginelli reaction.
spectrometer and chemical shifts were recorded as ppm downfield
from internal tetramethylsilane. The mass spectra were taken on a
Waters ZQ Micromass LC/MS spectrometer. Elemental analyses
were performed on a Leco 932 CHNS instrument. Reaction prog-
ress was monitored by TLC on precoated aluminum‐backed
plates (Merck SIL G/UV254) and chromophoric compounds were
visualized by UV light and subsequent staining with alkaline po-
tassium permanganate solution or iodine.
For comparison purposes, DHPMs were prepared using
three different procedures (Scheme 1). Our initial attempts
focused on the catalyzed Biginelli reaction which involves
condensation of β‐keto ester, aldehyde and urea/thiourea
under solvent‐free conditions. In the case of MgBr2 as a
catalyst, we found that its isolated yield was higher than when
MgCl2·6H2O was used as a catalyst. Magnesium chloride
hexahydrate was very much moisture sensitive. Therefore,
we determined that MgBr2 as the best catalyst for the Biginelli
reaction. In the course of our work, we utilized the same
synthetic procedure of Salehi [61–63] and Zhang [64]. All
the synthesized DHPMs were new and not reported elsewhere.
In the final experimental procedure, a mixture of β‐keto
ester, aldehyde and urea/thiourea was heated at 100°C in a
little amount of EtOH without catalyst [65]. For all the
cases, the catalyzed methods (methods I and II) produced
significantly shorter reaction time (45–120 min) and better
reaction yields (75–91%) than the catalyst‐free Biginelli re-
action [65]. This indicates the special advantage of the sol-
ventless and catalyzed Biginelli reaction.
General procedure for the one‐pot synthesis of 3,
4‐dihydropyrimidinones under solvent‐free conditions.
Method
I (catalyst: MgBr2). The mixture of aldehyde
(2 mmol), β‐keto ester (2 mmol), urea/thiourea (3 mmol), and
MgBr2 (0.2 mmol, 10% mol) was heated at 100°C with stirring
until the mixture turned to solid mass. After the completion of the
reaction (monitored by TLC), the solid was cooled to room
temperature and poured onto crushed ice (20 g) and stirred for
10 min. The crude product was filtered, washed with cold water
(2 × 10 mL), and then recrystallized from either ethanol or ethyl
acetate/hexane to afford pure products.
Method II (catalyst: MgCl2·6H2O). The mixture of aldehyde
(2 mmol), β‐keto ester (2 mmol), urea/thiourea (3 mmol), and
MgCl2·6H2O (0.4 mmol, 20% mol) was heated at 80°C with
stirring until the mixture turned to solid mass. After the
completion of the reaction (monitored by TLC), the solid was
cooled to room temperature and poured onto crushed ice (20 g)
and stirred for 10 min. The crude product was filtered, washed
with cold water (2 × 10 mL), and then recrystallized from either
ethanol or ethyl acetate/hexane to afford pure products.
Method III (without catalyst). The solution of aldehyde
(2 mmol), β‐keto ester (2 mmol), and urea/thiourea (3 mmol) in
EtOH (2 mL) was heated at 100°C with stirring. After the reaction
completion (monitored by TLC), the resulting mixture was then
poured onto crushed ice (20 g), and solid product separated was
filtered and recrystallization from ethanol provides the pure products.
5‐Ethoxycarbonyl‐6‐methyl‐4‐(5‐methylthiophen‐2‐yl)‐3,4‐
dihydropyrimidin‐2(1H)‐one (4a). White crystals. Rf = 0.23
(50% ethyl acetate/hexane). IR (ATR, neat): 3233, 3110, 2971,
1723, 1702, 1650 cm−1. 1H‐NMR (400 MHz, DMSO‐d6): 9.27
(s, 1H, NH), 7.83 (s, 1H, NH), 6.65 (d, 1H, J = 3.4 Hz, Har),
6.60 (m, 1H, Har), 5.31 (d, 1H, J = 3.5 Hz, CH), 4.07 (q, 2H,
J = 7.1 Hz, OCH2CH3), 2.36 (s, 3H, CH3), 2.21 (s, 3H, CH3),
1.18 (t, 3H, J = 7.1 Hz, OCH2CH3). 13C‐NMR (100 MHz, DMSO‐
d6): 165.5, 152.72, 148.95, 146.67, 138.41, 125.10, 123.69, 100.24,
59.79, 49.91, 18.12, 15.42, 14.64. MS (ES+): m/z (%) = 344.41
The results indicated that steric hindrance and the long
chain of the R2 (Ot‐Bu and OAllyl) on the 1,3‐dicarbonyl
compound reduced the reaction yield (Table 1).
The plausible mechanism is given in Scheme 2. In this
mechanism, the first step of the reaction between aldehyde 1
and urea/thiourea 2 includes the formation of the acyl imine
intermediate like the Schiff’s base (a conjugated imino‐ketone
as a Michael acceptor) which is stabilized by the magnesium
ion followed by β‐carbonyl carbon of the β‐carbonyl enolate
attack on the imine carbon produces an open‐chain ureide
which subsequently cyclizes to six‐member heterocyclic
compound. Dehydration leads to the DHPMs 4.
EXPERIMENTAL
The melting points were measured on an Electrothermal 9100
melting point apparatus and are uncorrected. The IR spectra were
recorded on a One FTIR ATR PerkinElmer spectrometer. The 1H‐
and 13C‐NMR spectra were taken with a Bruker 400 Ultra Shield
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Ş. Gülten
Vol 000
(M+ + Na + CH3CN, 71), 332.38 (M+ + 1 + CH3CN, 73), 281.37
(M+ + 1, 100). Anal. Calcd. for (C13H16N2O3S): C, 55.70; H, 5.75;
N, 9.99; S, 11.44. Found: C, 55.73; H, 5.65; N, 10.08; S, 11.42.
5‐tert‐Butoxycarbonyl‐6‐methyl‐4‐(5‐methylthiophen‐2‐yl)‐
3,4‐dihydropyrimidin‐2(1H)‐one (4b).Pale yellow crystals. Rf = 0.25
(50% ethyl acetate/hexane). IR (ATR, neat): 3233, 3110, 2976,
1718, 1699, 1645 cm−1. 1H‐NMR (400 MHz, DMSO‐d6): 9.15
(s, 1H, NH), 7.76 (s, 1H, NH), 6.64–6.61 (m, 2H, Har), 5.25
(d, 1H, J = 3.2 Hz, CH), 2.37 (s, 3H, CH3), 2.18 (s, 3H, CH3),
1.39 (s, 9H, (CH3)3C). 13C‐NMR (100 MHz, DMSO‐d6): 165.0,
152.8, 148, 146.82, 138.3, 125.0, 123.5, 101.6, 79.8, 50.13, 28.4,
18.1, 15.4. MS (ES+): m/z (%) = 372.51 (M+ + Na + CH3CN,
93), 350.42 (M+ + 1 + CH3CN, 83), 309.46 (M+ + 1, 100). Anal.
Calcd. for (C15H20N2O3S): C, 58.42; H, 6.54; N, 9.08; S, 10.40.
Found: C, 58.68; H, 6.18; N, 9.20; S, 10.46.
(C14H16N2O2S2·0.38H2O): C, 53.34; H, 5.36; N, 8.88; S, 20.34.
Found: C, 53.41; H, 5.07; N, 8.68; S, 19.95.
4‐(2‐Chloro‐5‐nitrophenyl)‐5‐ethoxycarbonyl‐6‐methyl‐3,4‐
dihydropyrimidin‐2(1H)‐one (4g). White solid. Rf = 0.31 (50%
ethyl acetate/hexane). IR (ATR, neat): 3339, 3228, 3113, 2976,
1
1701, 1642, 1575, 1524 cm−1. H‐NMR (400 MHz, DMSO‐d6):
9.45 (br s, 1H, NH), 8.14 (dd, 1H, J = 6.9, 1.8 Hz, Har), 8.07
(d, 1H, J = 1.7 Hz, Har), 7.90 (br s, 1H, NH), 7.76 (d, 1H, J = 8.7
Hz, Har), 5.72 (s, 1H, CH), 3.89 (q, 2H, J = 6.9 Hz, OCH2CH3 ),
2.33 (s, 3H, CH3), 1.02 (t, 3H, J = 7.2 Hz, OCH2CH3). 13C‐NMR
(100 MHz, DMSO‐d6): 164.65, 150.89, 150.10, 146.70, 143.57,
138.60, 131.11, 123.82, 123.64, 96.86, 59.25, 52.06, 17.72,
13.82. MS (ES+): m/z (%) = 381.52 (M+ + 1 + CH3CN, 64),
340.39 (M + + 1, 87).
5‐tert‐Butoxycarbonyl‐4‐(2‐chloro‐5‐nitrophenyl)‐6‐methyl‐
3,4‐dihydropyrimidin‐2(1H)‐one (4h). White solid. Rf = 0.24 (50%
ethyl acetate/hexane). IR (ATR, neat): 3368, 3227, 3097, 2968,
5‐Allyloxycarbonyl‐6‐methyl‐4‐(5‐methylthiophen‐2‐yl)‐3,4‐
dihydropyrimidin‐2(1H)‐one (4c). White solid. Rf = 0.28 (50%
ethyl acetate/hexane). IR (ATR, neat): 3413, 3245, 3114, 2946,
1
1710, 1648, 1574, 1520 cm−1. H‐NMR (400 MHz, DMSO‐d6):
1
1723, 1708, 1654 cm−1. H‐NMR (400 MHz, DMSO‐d6): 9.34
9.38 (br s, 1H, NH), 8.22 (dd, 1H, J = 6.1, 2.7 Hz, Har), 8.09
(d, 1H, J = 2.7 Hz, Har), 7.96 (br s, 1H, NH), 7.84 (d, 1H, J = 8.9
Hz, Har), 5.71 (d, 1H, J = 2.3 Hz, CH), 2.36 (s, 3H, CH3), 1.25
(s, 9H, (CH3)3C). 13C‐NMR (100 MHz, DMSO‐d6): 164.08,
151.43 149.93, 147.07, 143.73, 139.36, 131.74, 124.33, 123.92,
98.23, 79.99, 28.22, 18.13, 14.32. MS (ES+): m/z (%) = 390.54
(M+ + Na, 100), 368.54 (M+ + 1, 10).
(s, 1H, NH), 7.85 (s, 1H, NH), 6.65 (d, 1H, J = 3.3 Hz, Har),
6.61–6.60 (m, 1H, Har), 5.86–5.94 (m, 1H, CH2═CH), 5.34
(d, 1H, J = 3.4 Hz, CH2═CH), 5.24 (m, 1H, CH2═CH), 5.16
(s, 1H, CH), 4.55 (d, 2H, J = 5.2 Hz, CH2O), 2.36 (s, 3H, CH3),
2.23 (s, 3H, CH3). 13C‐NMR (100 MHz, DMSO‐d6): 165.1,
152.6, 149.6, 146.6, 138.5, 133.5, 125.2, 123.8, 117.6, 99.9,
64.3, 49.8, 18.21, 15.4. MS (ES+): m/z (%) = 356.33 (M+ + Na
+ CH3CN, 47), 334.38 (M+ + 1 + CH3CN, 75), 293.45 (M+ + 1,
100). Anal. Calcd. for (C14H16N2O3S): C, 57.52; H, 5.52; N,
9.58; S, 10.97. Found: C, 57.33; H, 5.32; N, 9.45; S, 10.74.
5‐Ethoxycarbonyl‐6‐methyl‐4‐(5‐methylthiophen‐2‐yl)‐3,4‐
dihydropyrimidin‐2(1H)‐thione (4d). Pale yellow crystals. Rf = 0.72
(50% ethyl acetate/hexane). IR (ATR, neat): 3318, 3168, 3102, 1698,
5‐Allyloxycarbonyl‐4‐(2‐chloro‐5‐nitrophenyl)‐6‐methyl‐3,4‐
dihydropyrimidin‐2(1H)‐one (4i). White solid. Rf = 0.21 (50%
ethyl acetate/hexane). IR (ATR, neat): 3226, 3099, 2958, 1706,
1
1651, 1575, 1527 cm−1. H‐NMR (400 MHz, DMSO‐d6): 9.66
(br s, 1H, NH), 8.19 (dd, 1H, J = 5.9, 2.7 Hz, Har), 8.12 (d, 1H,
J = 2.7 Hz, Har), 7.98 (br s, 1H, NH), 7.79 (1H, d, J = 8.7 Hz,
Har), 5.80–5.76 (m, 2H, CH2═CH and CHNH), 5.12–5.08 (m,
2H, CH2═CH), 4.48–4.47 (m, 2H, OCH2), 2.24 (s, 3H, CH3).
13C‐NMR (100 MHz, DMSO‐d6): 164.79, 151.38, 151.14,
147.19, 143.84, 139.17, 133.18, 131.16, 124.36, 124.08,
117.59, 97.05, 64.35, 52.52, 18.34. MS (ES+): m/z (%) =
393.57 (M+ + 1 + CH3CN, 100), 352.34 (M+ + 1, 77).
4‐(2‐Chloro‐5‐nitrophenyl)‐5‐ethoxycarbonyl‐6‐methyl‐3,4‐
dihydropyrimidin‐2(1H)‐thione (4j). Pale yellow solid. Rf = 0.72
(50% ethyl acetate/hexane). IR (ATR, neat): 3320, 3188, 3107,
2985, 1713, 1682, 1651, 1558, 1522 cm−1. 1H‐NMR (400 MHz,
DMSO‐d6): 10.54 (br s, 1H, NH), 9.74 (br s, 1H, NH), 8.17
(dd, 1H, J= 6.0, 2.7 Hz, Har), 8.06 (d, 1H, J = 2.7 Hz, Har),
7.76 (d, 1H, J = 8.8 Hz, Har), 5.74 (d, 1H, J = 2.8 Hz, CH),
3.93 (q, 2H, J = 7.1 Hz, OCH2CH3), 2.35 (s, 3H, CH3), 1.01
(t, 3H, J = 7.1 Hz, OCH2CH3). 13C‐NMR (100 MHz, DMSO‐d6):
174.48, 164.96, 147.14, 146.77, 142.81, 139.31, 131.76, 124.70,
99.21, 60.12, 52.69, 17.56, 14.27. MS (ES+): m/z (%) = 358.42
(M+ + 2, 37), 356.43 (M+ + 1, 100).
5‐tert‐Butoxycarbonyl‐4‐(2‐chloro‐5‐nitrophenyl)‐6‐methyl‐
3,4‐dihydropyrimidin‐2(1H)‐thione (4k). Pale yellow solid. Rf = 0.76
(50% ethyl acetate/hexane). IR (ATR, neat): 3330, 3170, 3105,
2950, 1711, 1653, 1585, 1520 cm−1. 1H‐NMR (400 MHz,
DMSO‐d6): 10.44 (br s, 1H, NH), 9.64 (br s, 1H, NH), 8.20
(dd, 1H, J = 6.0, 2.7 Hz, Har), 8.03 (d, 1H, J = 2.7 Hz, Har), 7.80
(d, 1H, J = 8.8 Hz, Har), 5.67 (d, 1H, J = 2.46 Hz, CH), 2.23
(s, 3H, CH3), 1.21 (s, 9H, (CH3)3C). 13C‐NMR (100 MHz,
DMSO‐d6): 173.94, 163.87, 146.48 145.66, 141.87, 139.06,
131.43, 124.15, 99.62, 80.13, 52.58, 30.66, 27.67, 17.00. MS (ES
+): m/z (%) = 386.61 (M+ + 3, 37), 384.57 (M+ + 1, 100).
1
1667, 1646, 1574 cm−1. H‐NMR (400 MHz, DMSO‐d6): 10.44
(s, 1H, NH), 9.72 (s, 1H, NH), 6.66 (d, 1H, J = 3.4 Hz, Har), 6.63
(m, 1H, Har), 5.32 (d, 1H, J = 3.3 Hz, CH), 4.08 (q, 2H, J = 7.1 Hz,
OCH2CH3), 2.37 (s, 3H, CH3), 2.26 (s, 3H, CH3), 1.17 (t, 3H,
J = 7.1 Hz, OCH2CH3). 13C‐NMR (100 MHz, DMSO‐d6): 175.04,
165.29 145.66, 144.90, 139.23, 125.30, 124.42, 101.64, 60.18,
49.88, 17.50, 15.43, 14.56. MS (ES+): m/z (%) = 297.40 (M+ + 1,
100). Anal. Calcd. for (C13H16N2O2S2·0.15H2O): C, 52.20; H,
5.49; N, 9.36; S, 21.43. Found: C, 51.93; H, 5.60; N, 9.43; S, 21.22.
5‐tert‐Butoxycarbonyl‐6‐methyl‐4‐(5‐methylthiophen‐2‐yl)‐
3,4‐dihydropyrimidin‐2(1H)‐thione (4e). Pale yellow crystals.
Rf = 0.76 (50% ethyl acetate/hexane), IR (ATR, neat): 3154,
3120, 2979, 1702, 1678, 1650, 1587 cm−1 1H‐NMR (400
.
MHz, DMSO‐d6): 10.33 (s, 1H, NH), 9.64 (s, 1H, NH), 6.65
(m, 2H, Har), 5.26 (d, 1H, J = 3.3 Hz, CH), 2.38 (s, 3H, CH3),
2.23 (s, 3H, CH3), 1.39 (s, 9H, CH3). 13C‐NMR (100 MHz,
DMSO‐d6): 175.05, 164.67 145.03, 144.84, 139.11, 125.20,
124.23, 102.97, 80.46, 50.10, 28.32, 17.48, 15.45. MS (ES+):
m/z (%) = 325.41 (M+ + 1, 100).
5‐Allyloxycarbonyl‐6‐methyl‐4‐(5‐methylthiophen‐2‐yl)‐3,4‐
dihydropyrimidin‐2(1H)‐thione (4f). Pale yellow crystals. Rf = 0.69
(50% ethyl acetate/hexane). IR (ATR, neat): 3315, 3173, 3106,
2998, 1738, 1723, 1578, 1663 cm−1. 1H‐NMR (400 MHz,
DMSO‐d6): 10.48 (br s, 1H, NH), 9.74 (br s, 1H, NH), 6.67
(d, 1H, J = 3.5 Hz, Har), 6.64 (m, 1H, Har), 5.90 (m, 1H, CH2═CH),
5.35 (s, 1H, CH), 5.20 (m, 2H, CH2═CH), 4.58 (d, 2H, J = 5.2 Hz,
OCH2), 2.37 (s, 3H, CH3), 2.28 (s, 3H, CH3). 13C‐NMR (100 MHz,
DMSO‐d6): 174.96, 164.90 146.25, 144.85, 139.30, 133.24,
125.37, 124.53, 117.78, 101.25, 64.62, 49.80, 17.59, 15.44. MS
#(ES+): m/z (%) = 309.36 (M+ + 1, 100). Anal. Calcd. for
5‐Allyloxycarbonyl‐4‐(2‐chloro‐5‐nitrophenyl)‐6‐methyl‐3,4‐
dihydropyrimidin‐2(1H)‐thione (4l). Pale yellow solid. Rf = 0.72
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
Magnesium Bromide and Magnesium Chloride Hexahydrate Catalyzed One-Pot Synthesis
of Dihydropyrimidines via Biginelli Reaction under Solvent-Free Conditions
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(50% ethyl acetate/hexane). IR (ATR, neat): 3377, 3308, 3267,
1
3176, 3004, 1712, 1645, 1609, 1523 cm−1. H‐NMR (400 MHz,
DMSO‐d6): 10.58 (br s, 1H, NH), 9.75 (br s, 1H, NH), 8.17
(dd, 1H, J = 6.1, 2.7 Hz, Har), 8.05 (d, 1H, J = 2.7 Hz, Har),
7.77 (d, 1H, J = 8.8 Hz, Har), 5.70–5.79 (m, 2H, CH2═CH and
CHNH), 5.08–5.00 (m, 2H, CH2═CH), 4.43–4.48 (m, 2H,
OCH2), 2.33 (s, 3H, CH3). 13C‐NMR (100 MHz, DMSO‐d6):
184.33, 174.51, 164.62, 147.22, 147.13, 142.60, 139.35,
132.97, 131.83, 124.73, 117.90, 98.91, 64.68, 52.67, 17.68. MS
(ES+): m/z (%) = 368.38 (M+ + 1, 100).
Acknowledgments. The author thanks to Çanakkale Onsekiz Mart
University (BAP 2008/28) for financial support. The author also
thanks to NMR Analysis Laboratory of Hacettepe University for
recording NMR spectra and Central Laboratory of Pharmacy,
Ankara University, for the measurement of the mass spectra and
elemental microanalyses.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet