Simple and efficient synthesis of 1,3-dithioles with pyrimidinylidene or pyrazolylidene substituents

Article abstract of DOI:10.1080/10426507.2010.551617

2-Pyrimidinylidene-1,3-dithioles or 2-pyrazolylidene-1,3-dithioles are prepared by a three-component condensation reaction of pyrimidine-tetraone or 1H-pyrazole-4,5-dione, carbon disulfide, and dialkyl acetylendicarboxylates in the presence of tributylpho

Full text of DOI:10.1080/10426507.2010.551617

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Phosphorus, Sulfur, and Silicon and the
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Simple and Efficient Synthesis of 1,3-
Dithioles with Pyrimidinylidene or
Pyrazolylidene Substituents
Ayoob Bazgir a & Ali Mohammad Astaraki a
a Department of Chemistry , Islamic Azad University , Doroud
Branch, Doroud, Iran
Published online: 24 Aug 2011.
To cite this article: Ayoob Bazgir & Ali Mohammad Astaraki (2011) Simple and Efficient Synthesis of
1,3-Dithioles with Pyrimidinylidene or Pyrazolylidene Substituents, Phosphorus, Sulfur, and Silicon and
the Related Elements, 186:9, 1916-1921, DOI: 10.1080/10426507.2010.551617
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Phosphorus, Sulfur, and Silicon, 186:1916–1921, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2010.551617
SIMPLE AND EFFICIENT SYNTHESIS OF 1,3-DITHIOLES
WITH PYRIMIDINYLIDENE OR PYRAZOLYLIDENE
SUBSTITUENTS
Ayoob Bazgir and Ali Mohammad Astaraki
Department of Chemistry, Islamic Azad University, Doroud Branch,
Doroud, Iran
GRAPHICAL ABSTRACT
Abstract 2-Pyrimidinylidene-1,3-dithioles or 2-pyrazolylidene-1,3-dithioles are prepared by
a three-component condensation reaction of pyrimidine-tetraone or 1H-pyrazole-4,5-dione,
carbon disulfide, and dialkyl acetylendicarboxylates in the presence of tributylphosphine.
Keywords 1; 3-Dithiole; acetylenic esters; 1H-pyrazole-3; 4-dione; pyrimidine-2; 4; 5; 6-
tetraone
INTRODUCTION
Simple nitrogen heteroarenes have received much attention in the literature over
the years. These compounds can be considered as potential building blocks in synthesis
and are found in a wide variety of pharmacologically and biologically active compounds.
The pyrimidine moiety is present in numerous natural products as well as in synthetic
pharmacophores with biological activities.1–3 Substituted pyrimidines, particularly with
amino groups in the 2 and 4 positions, are known pharmacophores in several structure-
based drug design approaches in medicinal chemistry.4,5 Similarly, heterocycles containing
the pyrazole ring are important targets in synthetic and medicinal chemistry because this
Received 29 November 2010; accepted 29 December 2010.
Address correspondence to Ayoob Bazgir, Department of Chemistry, Islamic Azad University, Doroud
Branch, Doroud 688173551, Iran. E-mail: a bazgir@yahoo.com
1916

SYNTHESIS OF 1,3-DITHIOLES
1917
fragment is a key moiety in numerous biologically active compounds,6–8 among them
prominent drug molecules such as Celecoxib, Pyrazofurine, and many others. Recently,
they have also emerged as potential atypical antipsychotics.9
Derivatives of sulfur heterocycles such as thiophene and 1,3-dithiole have been widely
explored as new materials because of their superconducting, optical, and electronic switch-
ing properties.10 1,3-Dithiol-2-ylidenes have attracted much attention as building blocks
for electronic materials due to their highly electron-donating properties.11,12 Therefore, due
to the importance of 1,3-dithioles, various methods have been reported for the synthesis of
1,3-dithiole derivatives.13–19
Therefore, as part of our program aimed at developing new methodologies for the
preparation of heterocycles,20–22 we report here an efficient synthesis of pyrimidinylidene-
1,3-dithioles or pyrazolylidene-1,3-dithioles.
RESULTS AND DISCUSION
The one-pot, three-component condensation reaction of dialkyl acetylenedicarboxy-
late 1, carbon disulfide 2, and pyrimidine-tetraone 3 in the presence of tributylposphine 4
proceeded rapidly in acetonitrile at room temperature, and was completed after 5–8 h to
afford the pyrimidinylidene-1,3-dithiole derivatives 5 in good yields (Table 1).
The good yields and purity of the products and the simplicity of the present procedure
make it an interesting, convenient, and acceptable one-pot method for the preparation of
functionalized pyrimidinylidene-1,3-dithioles. The compounds 5a–f are stable solids whose
structures were established by IR, 1H NMR, 13C NMR spectroscopy, and elemental analysis.
We have not established an exact mechanism for the formation of the
pyrimidinylidene-1,3-dithioles 5. However, a reasonable possibility is shown in
Scheme 1. Reaction of the tributylphosphine adduct 6 with acetylenedicarboxylate 1 leads
Table 1 Synthesis of 2-pyrimidinylidene-1,3-dithioles 5
Product 5
R
R’
Time (h)
Yield (%)a
a
b
c
d
e
f
Me
Me
Et
Et
tBu
tBu
Me
H
Me
H
Me
H
5
6
5
7
7
8
90
83
87
79
80
75
aIsolated yields.

1918
A. BAZGIR AND A. M. ASTARAKI
to 2-tributylphosphoranylidene-1,3-dithioles 7, which yield 5 by in situ Wittig reaction
with pyrimidine-tetraone 3.13
Scheme 1
As expected, when the pyrimidine-tetraone 3 was replaced by 3-methyl-1-phenyl-
1H-pyrazole-4,5-dione 8, the desired pyrazolylidene-1,3-dithioles 9 were obtained with
good yields under the same reaction conditions (Scheme 2).
Scheme 2
When benzil 10 was selected as an active carbonyl compound, the desired 1,3-dithiole
11 was obtained in moderate yield (Scheme 3).
Scheme 3

SYNTHESIS OF 1,3-DITHIOLES
1919
In summary, we have described a mild, facile, and three-component method for
the synthesis of 2-pyrimidinylidene-1,3-dithioles and 2-pyrazolylidene-1,3-dithioles using
readily available starting materials. Prominent among the advantages of this new method
are operational simplicity, good yields, and easy work-up procedures employed.
EXPERIMENTAL
Melting points were measured on an Electrothermal 9100 apparatus. Mass spectra
were recorded on a FINNIGAN-MAT 8430 mass spectrometer operating at an ionization
1
potential of 70 eV. H and 13C NMR spectra were recorded in DMSO-d6 on a BRUKER
DRX-300 AVANCE spectrometer at 300.13 and 75.47 MHz, respectively. IR spectra were
recorded using an FTIR apparatus (KBr pellets, νmax/cm−1). Elemental analyses were
performed using a Heraeus CHN-O-Rapid analyzer. The chemicals used in this work were
obtained from Fluka and Merck and were used without purification.
General Procedure for the Preparation of 1,3-Dithioles
To a magnetically stirred solution of CS2 (1 mmol) and tributylphosphine (1 mmol) in
CH3CN (5 mL) was added pyrazole-4,5-dione or pyrimidine-2,4,5,6-tetraone (1 mmol) and
dimethyl acetyenedicarboxylate (1 mmol) at room temperature. The mixture was finally
stirred for an appropriate time. After completion of the reaction (TLC), the reaction mixture
was filtered and the residue was washed with ether (10 mL) to afford the pure products.
Dimethyl 2-(1,3-dimethyl-2,4,6-trioxotetrahydropyrimidin-5(6H)-ylidene)-1,3-
◦
◦
dithiole-4,5-dicarboxylate (5a). Cream powder (yield 90%); mp 209 C–211 C. IR:
1737, 1716, 1701. 1H NMR: δ 3.31 (6H, s, 2CH3), 3.90 (6H, s, 2CH3). 13C NMR: δ 21.5,
23.8, 28.3, 54.4, 136.4, 150.5, 159.7, 160.7, 173.2. MS: m/z 372 (M+). Anal. Calcd. for
C13H12N2O7S2: C, 41.93; H, 3.25; N, 7.52. Found: C, 41.85; H, 3.33; N, 7.60.
Dimethyl 2-(2,4,6-trioxotetrahydropyrimidin-5(6H)-ylidene)-1,3-dithiole-4,5-
◦
◦
dicarboxylate (5b). Cream powder (yield 83%); mp 232 C–234 C. IR: 3034, 1730,
1709, 1696. 1H NMR: δ 3.88 (6H, s, 2CH3), 9.43 (2H, bs, 2NH). 13C NMR: δ 22.4, 27.2,
56.9, 135.4, 149.6, 159.4, 161.7, 17.9. MS: m/z 343 (M+). Anal. Calcd. for C11H8N2O7S2:
C, 38.37; H, 2.34; N, 8.14. Found: C, 38.44; H, 2.25; N, 8.21.
Diethyl 2-(1,3-dimethyl-2,4,6-trioxotetrahydropyrimidin-5(6H)-ylidene)-1,3-
dithiole-4,5-dicarboxylate (5c). Cream powder (yield 87%); mp 184 ◦C. IR: 2975, 2928,
1
3
1733, 1633. H NMR: δ 1.30 (6H, t, JHH = 7.04 Hz, 2CH3), 3.20 (6H, bs, 2CH3), 4.48
and 4.55 (4H, ABq, JHH = 6.98 Hz, 2CH2). 13C NMR: δ 14.1, 28.3, 63.7, 103.1, 136.4,
3
150.5, 159.3, 160.7, 173.1. MS: m/z 400 (M+). Anal. Calcd. for C15H16N2O7S2: C, 44.99;
H, 4.03; N, 7.00. Found: C, 44.90; H, 4.09; N, 6.91.
Diethyl
2-(2,4,6-trioxotetrahydropyrimidin-5(6H)-ylidene)-1,3-dithiole-4,5-
◦
◦
dicarboxylate (5d). Cream powder (yield 79%); mp 215 C–217 C. IR: 3038, 2920,
1
3
1728, 1704, 1654. H NMR: δ 1.33 (6H, t, JHH = 6.87 Hz, 2CH3), 4.32 and 4.34 (4H,
q, JHH = 6.87 Hz, 2CH2), 9.41 (2H, bs, 2NH). MS: m/z 372 (M+). Anal. Calcd. for
3
C13H12N2O7S2: C, 41.93; H, 3.25; N, 7.52. Found: C, 41.83; H, 3.16; N, 7.44.
Due to the very low solubility of 5d–f, we cannot report the 13C NMR data for these
products.
Di-tert-butyl 2-(1,3-dimethyl-2,4,6-trioxotetrahydropyrimidin-5(6H)-ylidene)-
1,3-dithiole-4,5-dicarboxylate (5e). Cream powder (yield 80%); mp > 300 ◦C. IR: 2975,
1
2939, 1720, 1717, 1634. H NMR: δ 1.54 (18H, s, 6CH3), 3.32 (6H, s, 2CH3). MS: m/z

1920
A. BAZGIR AND A. M. ASTARAKI
456 (M+). Anal. Calcd. for C19H24N2O7S2: C, 49.99; H, 5.30; N, 6.14. Found: C, 49.83;
H, 5.22; N, 6.05.
Di-tert-butyl 2-(2,4,6-trioxotetrahydropyrimidin-5(6H)-ylidene)-1,3-dithiole-4,
◦
5-dicarboxylate (5f). White powder (yield 75%); mp > 300 C. IR: 30245, 2970, 2943,
1
1717, 1703, 1631. H NMR: δ 1.43 (18H, s, 6CH3), 9.32 (2H, bs, 2NH). MS: m/z 428
(M+). Anal. Calcd. for C17H20N2O7S2: C, 47.65; H, 4.70; N, 6.54. Found: C, 47.54; H,
4.76; N, 6.62.
Dimethyl 2-(3-methyl-5-oxo-1-phenyl-1H-pyrazol-4(5H)-ylidene)-1,3-dithiole-
4,5-dicarboxylate (9a). Cream powder (yield 78%); mp 221 ◦C–223 ◦C. IR: 3087, 1719,
1705. 1H NMR: δ 2.23 (3H, s, CH3), 3.75 (3H, s, OCH3), 3.78 (3H, s, OCH3), 721–7.32
(5H, m, H-Ar). 13C NMR: δ 15.8, 50.3, 50.4, 117.5, 118.7, 126.7, 128.4, 139.3, 140.6,
146.2, 151.3, 165.2, 171.3. MS: m/z 390 (M+). Anal. Calcd. for C17H14N2O5S2: C, 52.30;
H, 3.61; N, 7.17. Found: C, 52.38; H, 3.55; N, 7.08.
Diethyl
2-(3-methyl-5-oxo-1-phenyl-1H-pyrazol-4(5H)-ylidene)-1,3-dithiole-
4,5-dicarboxylate (9b). Cream powder (yield 74%); mp 213 ◦C–215 ◦C. IR: 3081, 1715,
1
3
1711. H NMR: δ 1.23 (6H, t, JHH = 7.11 Hz, 2CH3), 2.26 (3H, s, CH3), 4.11 (4H, m,
2CH2), 7.20–7.33 (5H, m, H-Ar). 13C NMR: δ 14.3, 16.2, 57.3, 57.5, 117.7, 117.9, 125.2,
128.7, 138.6, 140.1, 145.9, 151.7, 166.0, 171.1. MS: m/z 418 (M+). Anal. Calcd. for
C19H18N2O5S2: C, 54.53; H, 4.34; N, 6.69. Found: C, 54.41; H, 4.26; N, 6.60.
Di-tert-butyl 2-(3-methyl-5-oxo-1-phenyl-1H-pyrazol-4(5H)-yl◦idene)-1,3-dithiole-
◦
4,5-dicarboxylate (9c). White powder (yield 68%); mp 232 C–234 C. IR: 3078, 1719,
1714. 1H NMR: δ 1.41 (18H, s, 6CH3), 2.29 (3H, s, CH3), 7.18–7.25 (5H, m, H-Ar). 13
C
NMR: δ 15.7, 28.3, 69.7, 116.4, 117.5, 125.9, 127.5, 138.1, 141.4, 145.3, 151.0, 166.5,
171.7. MS: m/z 474 (M+). Anal. Calcd. for C23H26N2O5S2: C, 58.21; H, 5.52; N, 5.90.
Found: C, 58.31; H, 5.46; N, 5.99.
Di-tert-butyl 2-(3-methyl-5-oxo-1-phenyl-1H-pyrazol-4(5H)-ylidene)-1,3-dithiole-
4,5-dicarboxylate (11). White powder (yield 48%); IR: 3023, 1714, 1709, 1704. 1H NMR:
δ 3.87 (3H, s, CH3), 3.91 (3H, s, CH3), 7.31–7.54 (10H, m, H-Ar). 13C NMR: δ 50.3, 50.4,
120.2, 127.5, 127.8, 128.3, 132.5, 134.8, 138.7, 138.9, 139.2, 167.9, 178.5. MS: m/z 412
(M+). Anal. Calcd. for C21H16O5S2: C, 61.15; H, 3.91. Found: C, 61.23; H, 3.84.
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1921
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