Synthesis of some biginelli compounds in solvent medium using a photochemistry method

Article abstract of DOI:10.1080/10426500307928

Some Biginelli compounds were synthesized by using a photochemistry method. The Biginell three-component cyclocondensation reactions in THF medium using a mixture of β-ketoester or β-diketone, arylaldehyde and (thio)urea under irradiation with a Wolframe

Full text of DOI:10.1080/10426500307928

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Phosphorus, Sulfur, and Silicon and the Related
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Synthesis of Some Biginelli Compounds in Solvent
Medium Using a Photochemistry Method
N. Foroughifar a , A. Mobinikhaledi a & H. Fathinejad Jirandehi a
a Arak University , Arak, Iran
Published online: 27 Oct 2010.
To cite this article: N. Foroughifar , A. Mobinikhaledi & H. Fathinejad Jirandehi (2003) Synthesis of Some Biginelli Compounds
in Solvent Medium Using a Photochemistry Method, Phosphorus, Sulfur, and Silicon and the Related Elements, 178:3, 495-500
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Phosphorus, Sulfur and Silicon, 2003, Vol. 178:495–500
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DOI: 10.1080/10426500390170624
SYNTHESIS OF SOME BIGINELLI COMPOUNDS
IN SOLVENT MEDIUM USING A
PHOTOCHEMISTRY METHOD
N. Foroughifar, A. Mobinikhaledi, and H. Fathinejad Jirandehi
Arak University, Arak, Iran
(Received August 13, 2002)
Some Biginelli compounds were synthesized by using a photochemistry
method. The Biginell three-component cyclocondensation reactions in
THF medium using a mixture of -ketoester or -diketone, arylaldehyde
and (thio)urea under irradiation with a Wolframe lamplight gave 1,4-
dihydropyrimidine-2(1H)-ones, DHPMs, in 70–95% yield after workup.
Keywords: 1,4-Dihydropyrimidine-2(1H)-ones; DHPM; photochemistry
INTRODUCTION
The first Biginelli compound was synthesized in 1893.1 Recently this re-
action has been extended for preparation of a large number of DHPMs.2
It is well established that various derivatives of pyrimidines, DHPMs,
exert interesting pharmacological efficiencies such as antitumor, an-
11
tiviral, and antibacterial activities.2
In the past decade DHPMs
with appropriate functional groups have emerged as antihypertensive
9
5
agents6 and potent calcium channel blockers.3 Thus, it seemed of
interest for us to prepare 1,4-dihydropyrimidine-2(1H)-ones, DHPMs,
with an improved procedure and in high yield. The most conve-
nient method for preparation of these compounds is condensation of a
-ketoester or -diketone 1, arylaldehyde 2, and (thio)urea 3 under
acidic conditions giving a low to moderate yield, in particular when sub-
stituted aromatic aldehydes or thioureas are used as starting materials.
The purpose of the present work is to extend the method of preparation
of pyrimidine derivatives of type 4 by using the photochemistry method
(Scheme 1).
Address correspondence to N. Foroughifar, Arak University, Chemistry Department,
Dr. Beheshti Avenue, Arak, Iran. E-mail: N Foroughifar@yahoo.com
495

496
N. Foroughifar et al.
SCHEME 1
RESULTS AND DISCUSSION
Reaction of the -ketoester or -diketone 1, appropriate aldehyde 2,
and (thio)urea 3 in THF under irradiation with a 100 W electrical lamp
afforded 4a–4m in high yields (see Table I). In each experiment a mo-
lar ratio 1.1:1:1.5 of the three components, 1, 2, and 3 were used as
reactants.12 The method is very simple and it can be used for different
-ketoesters or -diketones 1, appropriate aldehydes 2, and (thio)ureas
3 depending on Z, X, R groups to prepare various compounds. Substi-
tuted aldehydes or (thio)ureas can be used with no loss of yield (4a–4g,
4h–4m, see Table I) which is the advantage of this method as compared
with other methods.2,12–16 Solubility of impurities in THF as a solvent
is another advantage of this method, which distinguishes it from the
TABLE I 1,4-Dihydropyrimidine-2(1H)-ones, DHPMs (4a–4m)
Required
DHPMs
Z
X
R
time (h)
Yield (%)
4a
4b
4c
4d
4e
4f
4g
4h
4i
O
O
O
O
O
O
O
S
S
S
S
S
H
4-Cl
4-N(Me)2
H
4-Cl
4-NO2
2,5-(MeO)2
4-Me
4-N(Me)2
H
4-N(Me)2
4-Cl
4-MeO
Me
Me
Me
2.5
2
3
2.5
5
4
3
4
4
3
88
75
86
85
79
80
95
85
80
81
85
75
81
EtO
EtO
EtO
EtO
EtO
EtO
EtO
t-BuO
t-BuO
t-BuO
4j
4k
4l
4
5
4
4m
S

Synthesis of Some Biginelli Compounds in Solvent Medium
497
microwave-promoted preparation.12 Reactions were usually carried out
for 2 to 4 h. Yields of these one-pot protocol reactions following recrystal-
lization in ethanol were of the order of 70–95%, which is very favorable
as compared with a multistep method.17 Based on 1H NMR (500 MHz)
1
spectra these products exhibited high purity. In the H NMR spectra
of these compounds the two different broad signals at low field were
assigned to resonance of two NHs of the pyrimidine ring. This was
supported by IR spectra, which included signals in the region 3200–
1
3300 cm
.
In conclusion we have developed a simple and efficient practical
method for preparation of 1,4-dihydropyrimidine-2(1H)-ones, DHPMs,
in high yield, by using a 100 W electrical lamp.
EXPERIMENTAL
Melting points were determined on an electrothermal digital melting
point apparatus. 1H NMR spectra were recorded on a Bruker (500 MHz)
Spectrometer. The IR spectra were recorded on Galaxy FT-IR 5000 Spec-
trophotometer. Reactions were monitored by thin layer chromatogra-
phy. All commercial materials were used without purification.
General Procedure
A mixture of the -ketoester or -diketone (2.2 mmol) 1, appropriate
aldehyde 2 (2 mmol), (thio)urea (3 mmol) 3, and THF (25 ml) was stirred
while the set-up was irradiated from the top by a 100 W electrical lamp
for the desired time. For compounds 4a–4m, the clear solution converted
to a turbid solution after the required time. Then the mixture was kept
at room temperature for 5 h. The crude product was filtered off and re-
crystallized from ethanol to give pure product in 70–95% yields (Table I).
5-Acyl-6-methyl-4-phenyl-2-oxo-1,2,3,
4-tetrahydropyrimidine (4a)
Yield 88%, m.p. 219–221 C. IR (KBr): = 3260, 3050, 1700, 1620
cm 1. 1H-NMR (DMSO-d6): (ppm) = 2.1 (s, 3H, CH3), 2.3 (s, 3H, CH3),
5.1 (d, J = 2.4 Hz, 1H, H4), 7.2 (m, 5H, Harom), 7.9 (brs, 1H, NH), 8.7
(brs, 1H, NH).
5-Acyl-6-methyl-4-(4-chlorophenyl)-2-oxo-1,2,3,
4-tetrahydropyrimidine (4b)
Yield 75%, m.p. 223–225 C. IR (KBr): = 3289, 3050, 1699,
1619 cm 1. 1H-NMR (DMSO-d6): (ppm) = 2.1 (s, 3H, CH3), 2.3 (s, 3H,

498
N. Foroughifar et al.
CH3), 5.2 (d, J = 2.4 Hz, 1H, H4), 7.3 (m, 2H, Harom), 7.8 (brs, 1H, NH), 9.2
(s, 1H, NH).
5-Acyl-6-methyl-4-(4-dimethylaminophenyl)-2-oxo-1,2,3,
4-tetrahydropyrimidine (4c)
Yield 86%, m.p. 235–237 C. IR (KBr): = 3265, 3130, 3020, 1699,
1630 cm 1. 1H-NMR (DMSO-d6): (ppm) = 2.1 (s, 3H, CH3), 2.3 (s, 3H,
CH3), 5.3 (d, J = 2.4 Hz, 1H, H4), 7.2 (m, 2H, Harom), 7.4 (m, 2H, Harom),
7.7 (brs, 1H, NH), 8.5 (brs, 1H, NH).
Ethyl-6-methyl-4-phenyl-2-oxo-1,2,3,
4-tetrahydropyrimidine-5-carboxylate (4d)
Yield 86%, m.p. 202–204 C. IR (KBr): = 3245, 3120, 3040, 1730,
1710 cm 1. 1H-NMR (DMSO-d6): (ppm) = 1.1 (t, J = 7.2 Hz, 3H, CH3),
2.3 (s, 3H, CH3), 4.0 (q, 2H, J = 7.5, OCH2), 5.2 (d, J = 3.4 Hz, 1H,
H-4), 7.4 (m, 2H, Harom), 7.7 (brs, 1H, NH), 8.5 (brs, 1H, NH).
Ethyl-6-methyl-4-(4-chlorophenyl)-2-oxo-1,2,3,
4-tetrahydropyrimidine-5-carboxylate (4e)
Yield 79%, m.p. 214–216 C. IR (KBr): = 3242, 3118, 1724, 1702,
1648 cm 1. 1H-NMR (DMSO-d6): (ppm) = 1.1 (t, J = 7.2 Hz, 3H, CH3),
2.3 (s, 3H, CH3), 4.0 (q, J = 7.2 Hz, 2H, OCH2), 5.2 (d, J = 3.4 Hz, 1H,
H4), 7.4 (m, 4H, Harom), 7.8 (brs, 1H, NH), 9.2 (brs, 1H, NH).
Ethyl-6-methyl-4-(4-nitrophenyl)-2-oxo-1,2,3,
4-tetrahydropyrimidine-5-carboxylate (4f)
Yield 80%, m.p. 175–177.5 C. IR (KBr): = 3244, 3117, 1726,
1
1700 cm 1. H-NMR (DMSO-d6): (ppm) = 1.0 (t, 3H, CH3), 2.2 (s,
3H, CH3), 4.0 (q, J = 7.2 Hz, 2H, OCH2), 5.3 (d, J = 3.6 Hz, 1H, H4), 7.5
(m, 2H, Harom), 7.9 (brs, 1H, NH).
Ethyl-6-methyl-4-(2,5-dimethoxyphenyl)-2-oxo-1,2,3,
4-tetrahydropyrimidine-5-carboxylate (4g)
Yield 95%, m.p. 187–188.5 C. IR (KBr): = 3240, 3112, 1705,
1680 cm 1. 1H-NMR (DMSO-d6): (ppm) = 1.0 (t, J = 7.2 Hz, 3H, CH3),
2.3 (s, 3H, CH3), 3.8 (s, 6H, OCH3), 4.0 (q, 2H, OCH2), 5.2 (d, J = 3.6
Hz, 1H, H4), 7.2 (s, 1H, Harom)), 7.5 (m, 2H, Harom), 8.1 (brs, 1H, NH),
9.2 (brs, 1H, NH).
Ethyl-6-methyl-4-(4-methylphenyl)-2-thioxo-1,2,3,
4-tetrahydropyrimidine-5-carboxylate (4h)
1
Yield 85%, m.p. 185–187 C. IR (KBr): = 3325, 3177, 1674 cm
.
1H-NMR (DMSO-d6): (ppm) = 1.1 (t, J = 7.2 Hz, 3H, CH3), 2.3 (s, 6H,

Synthesis of Some Biginelli Compounds in Solvent Medium
499
2CH3), 4.0 (q, J = 7.2 Hz, 2H, OCH2), 5.2 (d, J = 3.6 Hz, 1H, H4), 7.2
(m, 4H, Harom)), 9.5 (brs, 1H, NH), 10.2 (brs, 1H, NH).
Ethyl-6-methyl-4-(4-dimethylaminophenyl)-2-thioxo-1,2,3,
4-tetrahydropyrimidine-5-carboxylate (4i)
Yield 80%, m.p. 248–250 C. IR (KBr): = 3240, 3100, 1730,
1700 cm 1. 1H-NMR (DMSO-d6): (ppm) = 1.1 (t, J = 7.2 Hz, 3H, CH3),
2.2 (s, 3H, CH3), 2.8 (s, 6H, N(CH3)2), 4.0 (q, J = 7.2 Hz, 2H, OCH2), 5.0
(d, J = 3.6 Hz, 1H, H4), 6.5 (m, 2H, Harom), 7.1 (m, 2H, Harom), 7.5 (brs,
1H, NH).
Ethyl-6-methyl-4-phenyl-2-thioxo-1,2,3,
4-tetrahydropyrimidine-5-carboxylate (4j)
Yield 80%, m.p. 206–208 C. IR (KBr): = 3340, 3180, 1703,
1675 cm 1. 1H-NMR (DMSO-d6): (ppm) = 1.1 (t, J = 7.2 Hz, 3H, CH3),
2.3 (s, 3H, CH3), 4.0 (q, J = 7.2 Hz, 2H, OCH2), 5.3 (d, J = 3.6 Hz, 1H,
H4), 7.3 (m, 5H, Harom), 9.6 (brs, 1H, NH), 10.3 (brs, 1H, NH).
tert-Butyl-6-methyl-4-(4-dimethylaminophenyl)-2-thioxo-
1,2,3,4-tetrahydropyrimidine-5-carboxylate (4k)
Yield 85%, m.p. 214–216 C. IR (KBr): = 3330, 3160, 3050, 1720,
1
1662 cm
.
1H-NMR (DMSO-d6): (ppm) = 1.3 (s, 9H, 3CH3), 2.24
(s, 3H, CH3), 2.8 (s, 6H, N(CH3)2), 5.12 (d, J = 3 Hz, 1H, H4), 6.8 (m, 2H,
H
arom), 7.3 (m, 2H, Harom), 7.5 (brs, 1H, NH), 9.0 (brs, 1H, NH).
tert-Butyl-6-methyl-4-(4-chlorophenyl)-2-thioxo-1,2,3,
4-tetrahydropyrimidine-5-carboxylate (4l)
Yield 75%, m.p. 209–211 C. IR (KBr): = 3220, 3180, 3010,
1
1705 cm
.
1H-NMR (DMSO-d6): (ppm) = 1.3 (s, 9H, 3CH3), 2.24
(s, 3H, CH3), 5.3 (d, J = 3.0 Hz, 1H, H4), 7.3 (m, 4H, Harom), 8.0 (brs,
1H, NH), 9.8 (brs, 1H, NH).
tert-Butyl-6-methyl-4-(4-methoxylphenyl)-2-thioxo-1,2,3,
4-tetrahydropyrimidine-5-carboxylate (4m)
Yield 81%, m.p. 185–187 C. IR (KBr): = 3280, 3150, 3045,
1
1705 cm
.
1H-NMR (DMSO-d6): (ppm) = 1.3 (s, 9H, 3CH3), 2.25
(s, 3H, CH3), 5.2 (d, J = 3.0 Hz, 1H, H4), 7.1 (m, 2H, Harom), 7.5 (m,
2H, Harom), 8.2 (brs, 1H, NH), 9.5 (brs, 1H, NH).
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