Studies on reactions of pyrimidine compounds: Synthesis and reactions of 5-benzoyl-4,6-diphenyl-1,2,3,4-tetrahydro-2-thioxopyrimidine

Article abstract of DOI:10.1080/10426500701263554

The 5-benzoyl-4,6-diphenyl-1,2,3,4-tetrahydro-2-thioxopyrimidin (1) have been prepared via Biginelli cyclocondensation reaction in acetic acid under reflux condition in good yield (93%). Reactions of 1 and iodomethane to afford thiopyrimidine compounds 3

Full text of DOI:10.1080/10426500701263554

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Studies on Reactions of
Pyrimidine Compounds:
Synthesis and Reactions of 5-
Benzoyl-4,6-Diphenyl-1,2,3,4-
Tetrahydro-2-Thioxopyrimidine
a
Furgan Aslanoğlu a , Esvet Akbaş , Mehmet Sönmez
a & Barış Anıl b
a Chemistry Department, Faculty of Arts and
Sciences , University of Yuzuncu Yil , Van, Turkey
b Chemistry Department, Faculty of Arts and
Sciences , University of Ataturk , Erzurum, Turkey
Published online: 07 Jun 2007.
To cite this article: Furgan Aslanoğlu , Esvet Akbaş , Mehmet Sönmez & Barış
Anıl (2007) Studies on Reactions of Pyrimidine Compounds: Synthesis and
Reactions of 5-Benzoyl-4,6-Diphenyl-1,2,3,4-Tetrahydro-2-Thioxopyrimidine,
Phosphorus, Sulfur, and Silicon and the Related Elements, 182:7, 1589-1597, DOI:
10.1080/10426500701263554
To link to this article: http://dx.doi.org/10.1080/10426500701263554
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Phosphorus, Sulfur, and Silicon, 182:1589–1597, 2007
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701263554
Studies on Reactions of Pyrimidine Compounds:
Synthesis and Reactions of 5-Benzoyl-4,6-Diphenyl-
1,2,3,4-Tetrahydro-2-Thioxopyrimidine
˘
Furgan Aslanoglu
Esvet Akbas¸
¨
Mehmet Sonmez
Chemistry Department, Faculty of Arts and Sciences,
University of Yuzuncu Yil, Van, Turkey
Barıs¸ Anıl
Chemistry Department, Faculty of Arts and Sciences,
University of Ataturk, Erzurum, Turkey
The 5-benzoyl-4,6-diphenyl-1,2,3,4-tetrahydro-2-thioxopyrimidin (1) have been pre-
pared via Biginelli cyclocondensation reaction in acetic acid under reflux condition
in good yield (93%). Reactions of 1 and iodomethane to afford thiopyrimidine com-
pounds 3 and 5. Also, the acetylation of compounds 1 and 3 gave 3-acetyl thioxopy-
rimidine 2 and methylthiopyrimidine 4, respectively. Thioxopyrimidine derivative
6 was synthesized from 1 and POCl3/DMF. Furthermore, the starting compound
1 were cyclized with various bromo compounds to the thiazolopyrimidine 7, 8, 9
and pyrimido[2,3-b]thiazine10 derivatives, in approximately 55–78% yields. The
purpose of synthesizing the thioxopyrimidine derivatives is because of the high bio-
logical activities. All of these derivatives have been characterized by analytical and
spectroscopic studies and the reaction mechanism is discussed.
Keywords Biginelli reaction; cyclocondensation; multicomponent reaction; one-pot con-
densation reactions; synthesis; tetrahydropyrimidine
Received December 4, 2006; accepted January 5, 2007.
This work was supported by the Scientific and Technical Research Council of Turkey
(TBAG 2392 103T136). The authors would like to thank Department of Chemistry, Faculty
of Arts and Sciences, Ataturk University, for providing spectroanalytical facilities and Dr.
Musa Turker from the Department of Biology, Faculty of Arts and Sciences, Yuzuncu Yil
University for his helpful comments.
Address correspondence to Esvet Akbas¸, Chemistry Department, Faculty of Arts
and Sciences, University of Yuzuncu Yil, Zeve Campus, 65080, Van, Turkey. E-mail:
esvakbas@hotmail.com
1589

˘
F. Aslanoglu et al.
1590
INTRODUCTION
Many condensed heterocyclic systems, particularly when substituted to
a pyrimidine ring, play an important role as analgesic (1a), antipyretic
(1b), antihypertensive (1c), and antiinflammatory drugs (1d), also as
pesticides (1e), herbicides (1f), plant growth regulators, and organic cal-
cium channel modulators (2). Thus, pyrimidines have been subjected to
a large variety of structural modifications in order to synthesize deriva-
tives with different biological properties.
Various synthesis methods have been reported in the literature for
the synthesis of pyrimidine derivatives.1−9 Most of them are based
on the simple Biginelli2k three-component cyclocondensation reaction.
This very simple one-pot, acid-catalyzed cyclocondensation reaction of
an β-diketone, arylaldehyde, and (thio)urea.
Herein, due to versatile biological properties of pyrimidine deriva-
tives, we have reported synthesis of 5-benzoyl-4,6-diphenyl-1,2,3,4-
tetrahydro-2-thioxopyrimidine10 (1), and its various derivatives via the
general method of Biginelli cyclocondensation reaction in good yield.
RESULTS AND DISCUSSION
The synthetic pathway employed in the preparation of 1 is outlined
in Scheme 1. The condensation of 1,3-diphenyl-1,3-propanedione, ben-
zaldehyde, and thiourea in acetic acid, catalyzed by HCl, proceeded
according to the Biginelli reaction.
The 3-acetyl thioxopyrimidine derivative 2 was prepared via reac-
tion of compound 1 with acetic anhydride. The 13C NMR spectrum of 2
SCHEME 1

Reactions of Pyrimidine Compounds
1591
revealed signals at δ 196.2 (C O, benzoyl), 180.2 (C S),11 175.2 (C O),
and 29.8 CH3. In 1H NMR spectra, the singlet at 2.9 ppm is due to the
resonance of the CH3 group of the acetyl. The singlet and multiplets
at 6.8 and 7.0–7.5 ppm are assigned to H-4 and to the aryl protons,
respectively. The NH proton gives broad signal at 8.5 ppm, in accord
with the expected reaction product.
When S-methylation of compound 1 in methanol6 was formed
5-benzoyl-4,6-diphenyl-1,4-dihydro-2-methylthio
pyrimidine
(3),
which upon acetylation gave 3-acetyl-5-benzoyl-4,6-diphenyl-4H-2-
methylthio pyrimidine (4). The acetylation compound 4 was supported
1
1
by H NMR spectrum. The H NMR spectrum showed that 2.6 and
2.5 singlet signals for methyl protons. The 13C NMR spectrum of 4
revealed signals at δ 26.1 and 16.9 methyl groups (See Experimental
section for details).
SCHEME 2
The methylation of compound 1 with methyl iodide in 1N sodium
hydroxide7 afforded the product 5-benzoyl-3-methyl-4,6-diphenyl-4H-
2-methylthio pyrimidine (5) (Scheme 2). It was identified on the basis of
its elemental analysis and spectra. Its IR spectrum showed absorption
1
bands at 1624 cm−1 due to C O. The H NMR spectrum of 5 exhib-
ited singlet signals at δ 5.8 H-4 and 2.8, 2.5 ppm due to CH3 protons,
respectively.
SCHEME 3

˘
F. Aslanoglu et al.
1592
The compound 1 was treated with phosphoros oxychloride in
dimethylformamide at room temperature,6 intermediate product was
readily formed, which upon hydrolysis gave the formyl derivative
6 (Scheme 3). In the 1H NMR spectra of 6, as a singled signal
at δ 9.9 was exhibited due to formyl proton (See experimental for
details).
The compound 7 was synthesized reaction of the starting pyrimi-
dine derivative 1 and 1,2-dibromoethane in dimethylformamide under
reflux. The signals of two NH function groups disappeared in the IR and
1H NMR spectra of compound 7. The 1H NMR spectrum of compound 7
revealed multiplet signals at δ 3.8–4.5 due to thiazole methylen protons.
Also reaction of 1 and 2-bromopropionic acid as a cyclocondensation
reagent in dioxane8 under reflux gave compound 8. The IR spectrum of
8 showed absorption band at 1737, 1634 cm−1 because of two carbonyl
absorption bands.
SCHEME 4
On the other hand, the reaction of 1 with 2-bromoacetic acid lead
to 6-benzoyl-5,7-diphenyl-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidine-
2,3-dione (9), whereas reaction with 3-bromopropionic acid afforded
7-benzoyl-6,8-diphenyl-4-oxo-2,3-dihydro-6H-pyrimido[2,3-b]thiazine
(10) (Scheme 4). In the IR spectra of compounds 9 and 10 absence of
the characteristic absorption signals of the of NH groups of starting
material, is good evidence of the expected reactions.

Reactions of Pyrimidine Compounds
1593
EXPERIMENTAL
Solvents were dried by refluxing with the appropriate drying agents
and distilled before use. Melting points were determined on an Elec-
trothermal Gallenkamp apparatus and are uncorrected. Microanaly-
ses were performed on LECO CHNS 932 Elemental Analyzer. The IR
spectra were obtained in as potassium bromide pellets using a Mattson
1
1000 FTIR spectrometer. The H and 13C NMR spectra were recorded
on Bruker Avance DPX-200 spectrometers, using TMS as an internal
standard. All experiments were followed by TLC using DC Alufolien
Kieselgel 60 F 254 Merck and Camag TLC lamp (254/366 nm).
5-Benzoyl-4,6-diphenyl-1,2,3,4-tetrahydro-2-thioxopyrimidine
(1)
(The synthesis method of 1 was not to be able to reached, in spite of it is
availablity from the product list of Aurora Fine Chemicals. Therefore,
we think that the method applied in the present study is different).
A mixture of 1,3-diphenyl-1,3-propanedione (0.3584 g, 1.6 mmol), ben-
zaldehyde (0.11 ml, 1.1 mmol), thiourea (0.084 g, 1.1 mmol), and 20 ml
of glacial acetic acid containing a few drops concentrated hydrochloric
acid was heated under reflux for 8 h. The solution was allowed several
hours to yield 0.38 g (93%) of product.
3-Acetyl-5-benzoyl-4,6-diphenyl-1,2,3,4-tetrahydro-2-thioxop-
yrimidine (2)
A mixture of 1 (0.370 g, 1 mmol) in acetic anhydride (3 ml) was heated
under reflux for 1 h, then the reaction mixture was allowed to cool
to room temperature, and poured over crushed ice and stirred for
several minutes. The separated solid filtered off, washed with water,
and recrystallized from ethanol to give 0.218 g (59%) of 2, m.p. 190–
191◦C, IR(KBr): 3200 (NH), 2962 (CH), 1708, 1628 (C O), 1608, 1576,
1
1271(C S)9 cm−1, H-NMR (CDCl3): δ 8.5 (bs, 1H, NH), 7.0–7.5 (m,
15H, Harom.), 6.8 (s, 1H, CH), 2.9 (s, 3H, -CH3), 13C NMR (CDCl3):
δ = 196.2 (C O, benzoyl) and 180.2 (C S)11, 175.2 (C O), 145.8, 140.4,
139.8, 133.8, 133.6, 132.9, 132.5, 131.2, 131.1, 130.8, 130.0, 129.7, 128.5,
117.5, 57.8, and 29.8 ppm (CH3). Anal. Calcd. for C25H20N2O2S (412).
C, 72.79; H, 4.89; N, 6.79. Found: C, 72.76; H, 4.56; N, 6.65.
5-Benzoyl-4,6-diphenyl-1,4-dihydro-2-methylthio
Pyrimidine (3)
A solution of 1 (0.370 g, 1 mmol) in 20 ml methanol and methyl iodide
(0.074 ml, 1.2 mmol) was added. The mixture was then refluxed for 2

˘
F. Aslanoglu et al.
1594
h, and after addition of pyridine (0.5 ml), the solution was refluxed for
another 10 min. The reaction mixture was cooled and poured into 100
ml of ice-water. The precipitate was filtered off and washed with water
and cyclohexane. Compound 3 was obtained in yield 0.2 g (54%). m.p.
138–139◦C, IR(KBr): 3382 (NH), 1624 (C O) cm−1, 1H-NMR (CDCl3): δ
8.3 (s, 1H, NH), 7.0–7.4 (m, 15H, Harom.), 5.7 (s, 1H, -CH), 2.5 (s, 3H,
-CH3). Anal. Calcd. for C24H20N2OS (384). C, 74.97; H, 5.24; N, 7.29.
Found: C, 75.42; H, 5.31; N, 7.67.
3-Acetyl-5-benzoyl-4,6-diphenyl-4H-2-methylthio
Pyrimidine (4)
A mixture of 3 (0.384 g, 1 mmol) in acetic anhydride (3 ml) was heated
under reflux for 1 h. The solvent was evaporated, then the oily residue
was treated with dry ether, and the formed crude product was recrys-
tallized from ethanol. Compound 4 was obtained in yield 0.058 g (15%).
m.p. 197–198◦C, IR(KBr): 1708, 1664 (C O) cm−1, 1H-NMR (CDCl3): δ
7.1–7.5 (m, 15H, Harom.), 6.7 (s, 1H, -CH), 2.6 (s, 3H, -CH3),and 2.5 (s,
3H, -CH3), 13C NMR (CDCl3): δ = 197.0 and 171.9 (C O), 158.2, 149.8,
140.2, 139.0, 137.5, 133.9, 131.2, 131.0, 130.8, 130.6, 130.2, 129.7, 129.5,
128.2, 123.4, 56.7, 26.1, and 16.9 ppm. Anal. Calcd. for C26H22N2O2S
(426). C, 73.21; H, 5.20; N, 6.57. Found: C, 73.23; H, 5.22; N,
6.56.
5-Benzoyl-3-methyl-4,6-diphenyl-4H-2-methylthio
Pyrimidine (5)
To a suspension of 1 (0.370 g, 1 mmol) in 1N sodium hydroxide (4 ml),
methyl iodide (0.24 ml, 3.85 mmol) was added. The reaction mixture
was stirred at room temperature for 2 h. The solid was precipitated,
collected, washed with water, and dried. Yield 0.35 g (95%), yellow crys-
tals (2-propanol), m.p. 210–211◦C, IR(KBr): 1624 cm−1 (C O), 1H-NMR
(DMSO-d6): δ 7.0–7.5 (m, 15H, Harom.), 5.8 (s, 1H, -CH), 2.8 (s, 3H,
CH3), 2.5 (s, 3H, CH3). Anal. Calcd. for C25H22N2OS (398). C, 75.35; H,
5.56; N, 7.03. Found: C, 75.38; H, 5.54; N, 6.98.
5-Benzoyl-4,6-diphenyl-3-formyl-1,2,3,4-tetrahydro-2-thioxo-
pyrimidine (6)
To a solution of 1 (0.370 g, 1 mmol) in dry DMF (6 ml); 0.168 ml POCl3
was added under stirring in an ice-bath. Stirring was continued at room
temperature for another 30 min, and then the solution was poured into
ice-water, filtered, dried, and recrystallized from ethanol to give 6. Yield

Reactions of Pyrimidine Compounds
1595
0.2 g (54%), m.p. 212–213◦C, IR(KBr): 3200 cm−1 (NH), 1703, 1625 cm−1
1
(C O), 1253 (C S), H-NMR (CDCl3): δ 9.9 (s, 1H, -CHO), 8.6 (s, 1H,
-NH), 7.0–7.5 (m, 15H, Harom.), 6.6 (s, 1H, -CH), 13C-NMR (CDCl3): δ
196.2 (C O, benzoyl), 179.9 (C S), 164.9 (C O, formyl), 143.1, 140.6,
139.7, 134.0, 133.6, 132.8, 131.0, 130.9, 130.89, 130.80, 130.6, 129.8,
128.7, 116.9, and 56.1. Anal. Calc. for C24 H18N2O2S(398). C, 72.34; H,
4.55; N, 7.03. Found: C, 72.32; H, 4.58; N, 7.07.
6-Benzoyl-5,7-diphenyl-3,5-dihydro-2H-thiazolo[3,2-a]-
pyrimidine (7)
Compound 7 was prepared as a HBr salt. To a solution of 1 (0.370 g,
1mmol) in dry DMF (5 ml); 1.1 mmol dibromoethane was added under
stirring and the reaction mixture was refluxed for 3 h. The solvent was
evaporated, then the oily residue was treated with dry ether, and the
formed crude product was recrystallized from ethanol. Yield 0.236 g
(64%). m.p. 274–275◦C, IR(KBr): 3055, 2763 (-CH), 1626 cm−1 (C O),
1H-NMR (DMSO-d6): δ 7.3–7.8 (m, 15H, Harom.), 5.3 (s,1H, -CH), 3.8–
4.5 (m, 4H, thiazole -CH2),13C-NMR (DMSO-d6): δ 193.2, 173.2, 170.3,
160.8, 137.3, 136.7, 136.2, 134.5, 133.5, 131.4, 131.0, 130.9, 130.6, 130.2,
129.9, 129.7, 58.8, 46.9, and 30.1.
6-Benzoyl-2-methyl-5,7-diphenyl-3-oxo-2,3-dihydro-5H-
thiazolo[3,2-a] Pyrimidine (8)
A mixture of 1 (0.370 g, 1mmol) and 2-bromopropionic acid (1 mmol)
in dioxane (5 ml) were refluxed for 1 to 2 h. The reaction mixture was
cooled and the precipitate filtered off and then washed with water. The
crude product was recrystallized from 2-propanol. Yield 0.064 g (15%).
1
m.p. 247–248◦C, IR(KBr): 1737, 1634 cm−1 (C O), H-NMR (DMSO-
d6): δ 7.1–7.9 (m, 15H, Harom.), 6.1 (s,1H, -CH), 4.6 (q,1H, -CH), 1.7
(d, 3H, -CH3). Anal. Calc. for C26H20N2O2S (424). C, 73.56; H, 4.75; N,
6.60. Found: C, 73.54; H, 4.76; N, 6.62.
6-Benzoyl-5,7-diphenyl-3-oxo-2,3-dihydro-5H-thiazolo[3,2-a]
Pyrimidine (9)
A mixture of 1 (0.370 g, 1mmol), bromoacetic acid (1.1 mmol), and an-
hydrous sodium acetate (2 mmol), acetic anhydride (1.2 ml) in acetic
acid (20ml) was heated under reflux for 1 h. The residue was treated
with water (100 ml), the precipitate filtered off, and the formed crude
product was recrystallized from 2-propanol. Compound 9 was obtained

˘
F. Aslanoglu et al.
1596
in yield 0.277 g (75%). mp 169–170◦C, IR(KBr): 1737, 1635 cm−1 (C O).
1H-NMR (CDCl3): δ 7.3–7.9 (m, 15H, Harom.), 6.0 (s, 1H, -CH), 3.9 (2H,
d, CH2, J = 8.8 Hz, A part of AB system), 3.8 (2H, d, CH2, J = 8.8 Hz,
B part of AB system). Anal. Calc. for C25H18N2O2S (410). C, 73.15; H,
4.42; N, 6.82. Found: C, 73.13; H, 4.41; N, 6.80.
7-Benzoyl-6,8-diphenyl-4-oxo-2,3-dihydro-6H-pyrimido[2,3-b]
Thiazine (10)
A mixture of 1 (0.370 g, 1 mmol), 3-bromopropionic acid (1.1 mmol),
anhydrous sodium acetate (2 mmol), and acetic anhydride (2 ml) in
acetic acid (20 ml) was heated under reflux for 2 h. The residue was
treated with water (100 ml), the precipitate filtered off, and the formed
crude product was recrystallized from 2-propanol. Compound 10 was
obtained in yield 0.288 g (78%). m.p. 202–203◦C, IR(KBr): 1699, 1624
cm−1 (C O), 1H-NMR (DMSO-d6): δ 7.0–7.8 (m, 15H, Harom.), 5.6 (s,1H,
-CH), 2.8–3.2 (m, 4H, thiazine -CH2). Anal. Calc. for C26H20N2O2S (424).
C, 73.56; H, 4.75; N, 6.60. Found: C, 73.58; H, 4.74; N, 6.58.
CONCLUSIONS
This article deals with the synthesis of the 5-benzoyl-4,6-diphenyl-
1,2,3,4-tetrahydro-2-thioxopyrimidine10 by Biginelli cyclocondensation
reaction under Bro¨nsted acid catalysis in acetic acid. This protocol
has got advantages of high yield (93%), and simple work-up proce-
dure. Thereafter, various derivatives of 5-benzoyl-4,6-diphenyl-1,2,3,4-
tetrahydro-2-thioxopyrimidine was prepared because of the high bio-
logical activity of the pyrimidine derivatives.1
REFERENCES
[1] N. A. Hassan, Molecules, 5, 827 (2000), references cited therein: (a) M. Pemmsin,
C. Lnu-Due, F. Hoguet, C. Gaultier, and J. Narcisse, Eur. J. Chem., 23, 543 (1988);
(b) P. A. S. Smith, and R. O. Kan, J. Org. Chem., 29, 2261 (1964); (c) A. Cannito, M.
Pemmsin, C. Lnu-Due, F. Hoguet, C. Gaultier, and J. Narcisse, Eur. J. Chem., 25,
635 (1990); (d) S. Nega, J. Aionso, A. Diazj, and F. Junquere, J. Heterocycl. Chem.,
27, 269 (1990); (e) S. Tetsuo, T. Mikio, H. Hidetoshi, H. Daijiro, and I. Akira, Jpn.
Kokai Tokyo Koho JP 62,132,884 (1987), Chem. Abstr., 107, 198350h (1987); (f) P. K.
Chakaravorty, W. J. Grelnlee, K. Dooseap, N. B. Mantlo, and A. A. Patchett, A.P.C.T.
Int. Appl. WO 92.20.687.156 (1992), Chem. Abstr., 118, 213104d (1993); (g) C. J.
Shishoo, and K. S. Jain, J. Heterocycl. Chem., 29, 883 (1992).
[2] C. O. Kappe, Molecules, 3, 1– 9 (1998), references cited therein: (a) R. A. Janis, P.
J. Silver, and D. Triggle, J. Adv. Drug Res., 16, 309 (1987); (b) F. Bossert, and W.
Vater, Med. Res. Rev., 9, 291 (1989); (c) H. Cho, M. Ueda, K. Shima, A. Mizuno, M.
Hayashimatsu, Y. Ohnaka, Y. Takeuchi, M. Hamaguchi, K. Aisaka, T. Hidaka, M.

Reactions of Pyrimidine Compounds
1597
Kawai, M. Takeda, T. Ishihara, K. Funahashi, F. Satah, M. Morita, and T. Noguchi, J.
Med. Chem., 32, 2399 (1989); (d) K. Atwal, G. C. Rovnyak, J. Schwartz, S. Moreland,
A. Hedberg, J. Z. Gougoutas, M. F. Malley, and D. M. Floyd, J. Med. Chem., 33, 1510
(1990); (e) K. S. Atwal, G. C. Rovnyak, S. D. Kimball, D. M. Floyd, S. Moreland, B.
N. Swanson, J. Z. Gougoutas, J. Schwartz, K. M. Smillie, and M. F. Malley, J. Med.
Chem., 33, 2629 (1990); (f) K. S. Atwal, B. N. Swanson, S. E. Unger, D. M. Floyd,
S. Moreland, A. Hedberg, and B. C. O’Reilly, J.Med. Chem., 34, 806 (1991); (g) G.
C. Rovnyak, K. S. Atwal, A. Hedberg, S. D. Kimball, S. Moreland, J. Z. Gougoutas,
B.C. O’Reilly, J. Schwartz, and M. F. Malley, J. Med. Chem., 35, 3254 (1992); (h)
G. J. Grover, S. Dzwonczyk, D. M. McMullen, C. S. Normadinam, P. G. Sleph, and
S. J. Moreland, J. Cardiovasc. Pharmacol, 26, 289 (1995); (i) M. Negwer, Organic-
Chemical Drugs and their Synonyms, (Akademie Verlag, Berlin, 1994). p02558; (j)
G. C. Rovnyak, S. D. Kimball, B. Beyer, G. Cucinotta, J. D. DiMarco, J. Gougoutas,
A. Hedberg, M. Malley, J. P. McCarthy, R. Zhang, and S. Moreland, J. Med. Chem.,
38, 119 (1995); (k) P. Biginelli, Gazz. Chim. Ital., 23, 360 (1893); (l) D. J. Triggle,
and S. Padmanabhan, Chemtracts: Org. Chem., 8, 191 (1995); (m) C. O. Kappe,
Tetrahedron, 49, 6937 (1993).
[3] A. B. A. Elgazzar, A. M. Gafaar, and H. N. Hafez, A. S. Aly, Phosphorus, Sulfur, and
Silicon, 181, 1859–1883 (2006).
[4] J. M. Xu, S. P. Yao, W. B. Wu, D. S. Lv, and X. F. Lin, Journal of Molecular Catalysis
B: Enzymatic, 35, 4–6, 122–127 (2005).
˙
¨
[5] H. Kutlu, and Farmaso¨tik Kimya, Heterosiklik Seri Ilac¸lar, (Ozkaya Matbaacılık,
˙
Istanbul, 1976), 1st ed., Chap. 4, pp. 627–634.
[6] C. O. Kappe and P. Roschger, J. Heterocyclic Chem., 26, 55 (1989).
[7] E. Kh. Ahmed, M. A. Ameen, and F. F. Abdel-latif, Phosphorus, Sulfur, and Silicon.,
181, 497–510 (2006).
[8] A. Mobinikhaledi, N. Forughifar, and F. Goodarzi,Phosphorus, Sulfur, and Silicon,
178, 2539–2543 (2003).
[9] A.A. Aly, Phosphorus, Sulfur, and Silicon, 181,1285–1298 (2006).
[10] Aurora Fine Chemicals Product List ck-0179 (2005).
[11] K. Z. Beresneviciote, Z. Beresnevıcıus, G. Mikulskiene, J. Kihlberg, and J. Brodde-
falk, Magnetic Resonance in Chem., 35, 553–555 (1997).