Iminophosphorane-mediated efficient synthesis of new fluorine-containing triazolo[4,5-d]pyrimidin-7-ones

Article abstract of DOI:10.1080/10426507.2011.590169

The carbodiimides 3, obtained from aza-Wittig reactions of the corresponding iminophosphorane 2 with 1 equiv. of aromatic isocyanates, were allowed to react in the presence of a catalytic amount of potassium carbonate or EtO^-Na⁺ with

Full text of DOI:10.1080/10426507.2011.590169

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Phosphorus, Sulfur, and Silicon and the
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Iminophosphorane-Mediated Efficient
Synthesis of New Fluorine-Containing
Triazolo[4,5-d]Pyrimidin-7-Ones
Tao Wang a , Xiao-Ming Xu a , Xi-Xian Ke a , Xue-Ying Liu a , Jin Luo a
& Bei-Xin Yi a
a Key Laboratory of Functional Small Organic Molecules, Ministry of
Education, College of Chemistry and Chemical Engineering , Jiangxi
Normal University , Nanchang , China
Published online: 05 Jan 2012.
To cite this article: Tao Wang , Xiao-Ming Xu , Xi-Xian Ke , Xue-Ying Liu , Jin Luo & Bei-Xin Yi
(2012) Iminophosphorane-Mediated Efficient Synthesis of New Fluorine-Containing Triazolo[4,5-
d]Pyrimidin-7-Ones, Phosphorus, Sulfur, and Silicon and the Related Elements, 187:2, 155-164, DOI:
10.1080/10426507.2011.590169
To link to this article: http://dx.doi.org/10.1080/10426507.2011.590169
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Phosphorus, Sulfur, and Silicon, 187:155–164, 2012
Copyright ꢀC Jiangxi Normal University
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2011.590169
IMINOPHOSPHORANE-MEDIATED EFFICIENT
SYNTHESIS OF NEW FLUORINE-CONTAINING
TRIAZOLO[4,5-d]PYRIMIDIN-7-ONES
Tao Wang, Xiao-Ming Xu, Xi-Xian Ke, Xue-Ying Liu, Jin Luo,
and Bei-Xin Yi
Key Laboratory of Functional Small Organic Molecules, Ministry of Education,
College of Chemistry and Chemical Engineering, Jiangxi Normal University,
Nanchang, China
GRAPHICAL ABSTRACT
Abstract The carbodiimides 3, obtained from aza-Wittig reactions of the corresponding
iminophosphorane 2 with 1 equiv. of aromatic isocyanates, were allowed to react in the pres-
ence of a catalytic amount of potassium carbonate or EtO−Na+ with p-fluorothiophenol to give
5,6-disubstituted 1,2,3-triazolo[4,5-d]- pyrimidine-7-ones 5 in satisfactory yields. Further re-
action of compounds 5 with H2O2 or Na2WO4/H2O2 generated the corresponding compounds
6 and 7 in good yields, respectively.
Keywords aza-Wittig reaction; cyclization; synthesis; 1,2,3-Triazolo[4,5-d]pyrimidine-7-ones
INTRODUCTION
The synthesis of derivatives of triazolopyrimidines has been the focus of great interest
recently. This is due, in part, to the broad spectrum of biological properties of these
compounds. Some derivatives of them have shown remarkable biological properties, such
as antitumor, antiviral, Adenosine A2A Receptor antibacterial, and anti-HIV activities,1–5
whereas others exhibit good insecticidal, growth regulator, fungicidal activities, and can act
as anti-inflammatory agents.6–14 However, only a few reports are available on the herbicidal
activities of fluorine-containing triazolo[4,5-d]pyrimidine derivatives so far.
Received 10 April 2011; accepted 16 May 2011.
We thank the National Natural Science Foundation of China (No. 20862007) and the Natural Science
Foundation of Jiangxi Province in China (No. 2010GZH0070) for financial support.
Address correspondence to Tao Wang, Key Laboratory of Functional Small Organic Molecules, Ministry
of Education, College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, 330022
China. E-mail: wangtao1962@sohu.com
155

156
T. WANG ET AL.
Fluorine is a very unique element with the highest electronegativity as well as
high thermal stability and lipophilicity, which imparts various prominent functionalities
to organofluorine compounds. Therefore, fluorinated compounds in general and fluorinated
heterocycles in particular are the topic of many investigations.15 By introducing fluorine
atoms into organic molecule compounds with improved physical, chemical, and biological
properties are obtained.16,17 Some examples have demonstrated that the incorporation of
fluorine atoms or fluorine containing substituents into certain compounds influences their
herbicidal,18,19 fungicidal,20,21 and insecticidal activity.22
The aza-Wittig reactions of iminophosphoranes have received increasing attention
in view of their utility in the synthesis of N-heterocyclic compounds.23–25 Recently, we
have become interested in the synthesis of new bioactive heterocycles, such as triazolo[4,5-
d]pyrimidine-7-ones from various iminophosphoranes, with the aim of evaluating their
biological activities. Here, we report on the synthesis of 5,6-disubstituted-3-phenyl-1,2,3-
triazolo[4,5-d]pyrimidine-7-ones via a tandem aza-Wittig and cyclization reaction. Further,
the reaction of corresponding compound 5 with H2O2 or Na2WO4/H2O2 generates the
corresponding compounds 6 and 7, respectively, in good yields.
RESULTS AND DISCUSSION
Synthesis
The iminophosphorane 2 was obtained in satisfactory yield when 126 was treated
with triphenylphosphine, hexachloroethane, and Et3N. Iminophosphorane 2 in dry methy-
lene chloride reacted with aryl isocyanates to give carbodiimides 3. The direct reaction of
carbodiimides 3 with p-fluorothiophenol did not produce the 6-aryl-5-arylthio-3,6-dihydro-
3-phenyl-1,2,3-triazolo[4,5-d]pyrimidin-7-ones 5. Even in refluxing acetonitrile the inter-
mediate 4 did not cyclize. However, the reaction took place to give 5a–5f in good yields
under heating for 2–3 h in the presence of a catalytic amount of potassium carbonate.
The formation of 5 can be rationalized in terms of an initial nucleophilic addition of p-
fluorothiophenol to the corresponding carbodiimide 3 to give the intermediate 4 which
cyclizes to give 5a–5f (Scheme◦1). Irrespective of the substituents at the cyclization was
completed smoothly at 40–50 C. The results are listed in Table 1. It is interesting to
note that the carbodiimides 3 react with p-fluorothiophenol at room temperature to give
Scheme 1

IMINOPHOSPHORANE-MEDIATED EFFICIENT SYNTHESIS
157
Table 1 Yields of compounds 5a-5f
5
Ar
Ar1
Yield (%)
a
b
c
d
e
f
Ph
Ph
Ph
4-ClC6H4
4-ClC6H4
4-ClC6H4
Ph
89
96
87
87
84
83
4-ClC6H4
3-ClC6H4
Ph
4-ClC6H4
3-ClC6H4
the intermediate 4, which does not cyclize to give 5 even in refluxing MeCN/CH2Cl2 for
24 h. Also in refluxing EtOH/CH2Cl2, only the intermediate 4 was formed. However, in
the presence of a catalytic amount of EtO−Na+, compounds 3 were converted smoothly
into the 6-aryl-5-arylthio-3,6-dihydro-3-phenyl-1,2,3-triazolo[4,5-d]pyrimidin-7-ones 5a-f
in satisfactory yields at 40–50 ◦C within 0.5–1 h.
The direct reaction of compounds 5 with H2O2 gave 6-aryl-5-arylsulfinyl-3,6-
dihydro- 3-phenyl-1,2,3-triazolo[4,5-d]pyrimidine-7-ones 6 in good yields. The results
are listed in Table 2.
When compounds 5 were treated with H2O2 in the presence of a catalytic amount
of Na2WO4, the 6-aryl-5-arylsulfonyl-3,6-dihydro-3-phenyl-1,2,3-triazolo[4,5-d]-pyrimi-
din-7-ones 7 were obtained in satisfactory yields. The results are listed in Table 3.
Scheme 3
The structure of 1,2,3-triazolo[4,5-d]pyrimidine-7-ones 5, 6, and 7 was confirmed by
their spectroscopic data. For example, the IR spectrum of 6a shows C O absorption band
at 1746 cm−1. The 1H NMR spectrum of 6a displays multiplets at δ = 7.29–7.75 ppm due
to the aromatic protons. The 13C NMR spectrum of 6a shows signals for the C O moiety
and the pyrimidine ring at 156 ppm and at 155.9, 155.0, and 116.1 ppm, respectively. The
mass spectrum of the compound displays the molecule ion peak. All fragmentation ions
are consistent with the structure and can be clearly assigned.

158
T. WANG ET AL.
Table 2 Yields of compounds 6a-f
6
Ar
Ar1
Yield (%)
a
b
c
d
e
f
Ph
Ph
Ph
4-ClC6H4
4-ClC6H4
4-ClC6H4
Ph
77
80
79
70
77
74
4-ClC6H4
3-ClC6H4
Ph
4-ClC6H4
3-ClC6H4
EXPERIMENTAL
Melting points were measured with an electrothermal melting point apparatus and
are uncorrected. Mass spectra were measured with a Finnigan Trace MS spectrometer. IR
spectra were recorded with an FTS-185 infrared spectrometer as KBr pellets. 1H and 31
C
NMR spectra were recorded in CDCl3 or d6-DMSO as solvent with a Bruker AC-P400
spectrometer. Chemical shifts are given in ppm relative to TMS. Elementary analyses were
obtained with a Vario EL III instrument. All of the solvents and materials were reagent
grade and purified according to standard procedures.
Synthesis of Iminophosphorane 2
To a solution of 1 (2.26 g, 10 mmol) in MeCN (60 mL) was added Ph3P (7.86 g,
30 mmol), C2Cl6 (7.11 g, 30 mmol), and Et3N (6.06 g, 60 mmol) in this order. The mixture
was stirred for 3 h at ambient temperature. Then, the solvent was evaporated and the residue
was recrystallized from EtOH to give 2 in 90.7% yield; mp: 206–208 ◦C; 1H NMR (CDCl3,
400 MHz): δ = 1.05 (t, J = 6.8 Hz, 3H, CH2CH3), 3.91 (q, J = 7.2 Hz, 2H, CH2CH3),
7.37–7.75 (m, 20H, arom-H); Anal. Calcd. for C29H25N4O2P: C, 70.72; H, 5.12; N, 11.38;
Found: C, 70.47; H, 5.23; N, 11.57%.
Synthesis of 3,6-diaryl-3,6-dihydro-5-[(4-fluorophenyl)thio]-
1,2,3-triazolo[4,5-d]- pyrimidin-7-ones (5): General Procedure
To a solution of iminophosphorane 2 (3 mmol) in dry methylene chloride (15 mL),
the respective phenylisocyanate (3 mmol) was added under nitrogen at room temperature.
After the reaction mixture was left unstirred for 12–13 h the solvent was removed in
vacuo and anhydrous ethanol (10 mL) was added to precipitate triphenylphosphine oxide.
After triphenylphosphine oxide was separated by filtration from the filtrate the solvent was
Table 3 Yields of compounds 7a-f
7
Ar
Ar1
Yield (%)
A
B
C
D
E
F
Ph
Ph
Ph
4-ClC6H4
4-ClC6H4
4-ClC6H4
Ph
83
85
82
75
79
75
4-ClC6H4
3-ClC6H4
Ph
4-ClC6H4
3-ClC6H4

IMINOPHOSPHORANE-MEDIATED EFFICIENT SYNTHESIS
159
evaporated to give the corresponding carbodiimide 3, which was used directly without
further purification.
To a solution of 3, prepared as described above, in MeCN (25 mL) was added
p-fluorothiophenol (3 mmol) and a catalytic amount of solid K2CO3 (0.24 g, 2 mmol).
The mixture was stirred for 2–3 h at 50◦C and filtered. From the filtrate the solvent was
evaporated and the residue was recrystallized from dichloromethane/petroleum ether to
give the corresponding pure 6-aryl-5-arylthio-3,6-dihydro-3-phenyl-1,2,3- triazolo[4, 5-
d]pyrimidin-7-one 5.
3,6-Dihydro-3,6-diphenyl-5-[(p-fluorophenyl)thio]-1,2,3-
triazolo[4,5-d]pyrimi- dine-7-one (5a)
White solid; yield 89%; mp: 250–252 ◦C; IR (KBr): ν = 1734 (C O); 1592, 1527,
1218, 714 cm−1; 1H NMR (CDCl3, 400 MHz): δ = 7.19–7.83 (m, 14H, arom-H); 13C NMR
(d6-DMSO): δ = 165.3 (C O), 155.3, 146.5, 137.8, 137.7, 137.6, 137.0, 135.8, 134.8,
130.7, 130.3, 130.2, 129.9, 129.8, 129.7, 129.3, 129.1, 128.4, 127.8, 126.4, 120.1, 120.0;
MS (EI, m/z,%): 415 (M+ 23), 414 (9), 386 (13), 219 (43), 95 (78), 92 (57), 77 (100); Anal.
Calcd. for C22H14FN5OS: C 63.60, H 3.40, N 16.86; Found C 63.22, H 3.59, N 16.97%.
6-(4-Chlorophenyl)-3,6-dihydro-5-[(p-fluorophenyl)thio]-3-phenyl-
1,2,3-triazolo-[4,5-d]pyrimidine-7-one (5b)
White solid; yield 96%; mp: 220–222 ◦C; IR (KBr): ν = 1737 (C O), 1591, 1524,
1216, 735 cm−1; 1H NMR (CDCl3, 400 MHz): δ = 7.27–7.79 (m, 13H, arom-H); 13C NMR
(d6-DMSO): 166.1 (C O), 155.2, 145.4, 137.9, 137.6, 137.3, 137.0, 135.7, 134.6, 130.7,
130.5, 130.4, 129.8, 129.6, 129.5, 129.2, 129.0, 128.5, 127.7, 126.4, 120.2, 120.0; MS (EI,
m/z,%): 449 (M+ 27), 414 (10), 386 (5), 219 (41), 111 (100), 95 (49), 92 (78), 77 (69);
Anal. Calcd. for C22H13ClFN5OS: C 58.73, H 2.91, N 15.57; Found C 58.87, H 3.04, N
15.77%.
6-(3-Chlorophenyl)-3,6-dihydro-5-[(p-fluorophenyl)thio]-3-phenyl-
1,2,3-triazolo-[4,5-d]pyrimidine-7-one (5c)
White solid; yield 87%; mp: 140–142 ◦C; IR (KBr): ν = 1750 (C O); 1594, 1524,
1215, 734 cm−1; 1H NMR (CDCl3, 400 MHz): δ = 7.20–7.81 (m, 13H, arom-H); 13C NMR
(d6-DMSO): δ = 165.5 (C O), 155.3, 146.6, 137.9, 137.7, 137.5, 137.0, 135.7, 134.5,
131.3, 130.2, 130.0, 129.7, 129.5, 129.3, 129.1, 128.8, 128.4, 127.4, 126.6, 120.6, 120.1;
MS (EI, m/z,%): 449 (M+ 43), 414 (32), 386 (6), 219 (42), 111 (100), 95 (52), 92 (79), 77
(72); Anal. Calcd. for C22H13ClFN5OS: C 58.73, H 2.91, N 15.57; Found C 58.82, H 3.02,
N 15.62%.
3-(4-Chlorophenyl)-3,6-dihydro-5-[(p-fluorophenyl)thio]-6-phenyl-
1,2,3-triazolo-[4,5-d]pyrimidine-7-one (5d)
White solid; yield 87%; mp: 272–274 ◦C; IR (KBr): ν = 1739 (C O), 1592, 1523,
1215, 719 cm−1; 1H NMR (CDCl3, 400 MHz): δ = 7.03–7.60 (m, 13H, arom-H); 13C NMR
(d6-DMSO): δ = 165.2 (C O), 155.1, 146.5, 137.7, 137.6, 137.4, 137.1, 135.2, 134.6,
130.9, 130.2, 130.0, 129.9, 129.7, 129.6, 129.3, 129.1, 128.3, 127.7, 126.3, 120.2, 120.0;
MS (EI, m/z,%): 449 (M+ 28), 414 (12), 386 (9), 219 (47), 111 (100), 95 (58), 92 (72), 77

160
T. WANG ET AL.
(65); Anal. Calcd. for C22H13ClFN5OS: C 58.73, H 2.91, N 15.57; Found C 58.60, H 2.98,
N 15.76%.
3,6-Bis(4-chlorophenyl)-3,6-dihydro-5-[(p-fluorophenyl)thio]-
1,2,3-triazolo[4,5-d]pyrimidine-7-one (5e)
White solid; yield 84%; mp: 241–243 ◦C; IR (KBr): ν = 1733 (C O); 1591, 1523,
1218, 742 cm−1; 1H NMR (CDCl3, 400 MHz): δ = 7.22–7.77 (m, 12H, arom-H); 13C NMR
(d6-DMSO): δ = 166.2 (C O), 155.5, 146.7, 140.7, 137.7, 136.3, 136.1, 135.0, 134.8,
130.7, 130.3, 130.2, 129.9, 129.8, 129.7, 129.3, 129.1, 128.4, 127.9, 124.5, 120.1, 120.0;
MS (EI, m/z,%): 485/483 (M+ 11/32), 448 (9), 420 (3), 309 (21), 219 (32), 111 (100), 95
(62), 92 (81), 77 (45); Anal. Calcd. for C22H12Cl2FN5OS: C 54.56, H 2.50, N 14.46; Found
C 54.41, H 2.30, N 14.57%.
3-(4-Chlorophenyl)-6-(3-Chlorophenyl)-3,6-dihydro-5-
[(p-fluorophenyl)thio]-
1,2,3-triazolo[4, 5-d]pyrimidine-7-one (5f)
White solid; yield 83%; mp: 216–217 ◦C; IR (KBr): ν = 1742 (C O); 1589, 1504,
1214, 735 cm−1; 1H NMR (CDCl3, 400 MHz): δ = 7.22–7.79 (m, 12H, arom-H); 13C NMR
(d6-DMSO): δ = 164.9 (C O), 155.2, 146.5, 137.9, 137.8, 137.7, 137.6, 137.2, 137.1,
135.8, 133.1, 130.6, 130.5, 130.0, 129.9, 129.8, 129.2, 129.1, 127.7, 126.0, 120.2, 120.1;
MS (EI, m/z,%): 485/483 (M+ 8/29), 448 (6), 420 (4), 309 (16), 219 (42), 111 (100), 95
(56), 92 (78), 77 (25); Anal. Calcd. for C22H12Cl2FN5OS: C 54.56, H 2.50, N 14.46; Found
C 54.41, H 2.62, N 14.58%.
Synthesis of 3,6-Diaryl-3,6-dihydro-5-[(p-fluorophenyl)sulfinyl]-
1,2,3-triazolo[4, 5-d]pyrimidin-7-ones (6): General Procedure
Compound 5 (27 mmol) and 20 mL of anhydrous acetic acid were poured into a 50
mL flask. After mixing 30% H2O2 (6.12 g, 54 mmol) was added dropwise to the reaction
mixture. The reaction mixture was stirred at 45–50 ◦C for 3 h. The progress of the reaction
was monitored by TLC. After stirring for another 0.5 h at room temperature 3.4 g of
Na2SO3 in 60 mL of water was added. The solid formed was filtered and recrystallized
from DMSO/ethanol to give pure compound 6 as a white crystalline solid.
3,6-Dihydro-3,6-diphenyl-5-[(p-fluorophenyl)sulfinyl]-
1,2,3-triazolo[4,5-d]pyri- midine-7-one (6a)
White solid; yield 77%; mp: 283–285 ◦C; IR (KBr): ν = 1746 (C O); 1595, 1524,
1218, 752 cm−1; 1H NMR (CDCl3, 400 MHz): δ = 7.29–7.75 (m, 14H, arom-H); 13C NMR
(d6-DMSO): δ = 156.0 (C O), 155.9, 155.0, 150.5, 144.1, 140.6, 135.6, 134.5, 133.6,
133.1, 133.0, 132.6, 132.2, 130.3, 130.1, 129.7, 129.4, 128.7, 127.2, 124.4, 120.8, 116.1;
MS (EI, m/z,%): 431 (M+ 14), 403 (6), 312 (11), 235 (44), 95 (68), 92 (18), 77 (100); Anal.
Calcd. for C22H14FN5O2S: C 61.24, H 3.27, N 16.23; Found C 61.11, H 3.32, N 16.33%.
6-(4-Chlorophenyl)-3,6-dihydro-5-[(p-fluorophenyl)sulfinyl]-3-phenyl-
1,2,3-tri- azolo[4,5-d]pyrimidine-7-one (6b)
◦
White solid; yield 80%; mp: >300 C; IR (KBr): ν = 1745 (C O); 1593, 1524,
1214, 737 cm−1; 1H NMR (CDCl3, 400 MHz): δ = 7.32–7.68 (m, 13H, arom-H); 13C NMR
(d6-DMSO): δ = 155.8 (C O), 155.0, 152.2, 150.3, 140.7, 135.9, 135.2, 134.5, 134.0,
133.5, 132.9, 131.1, 130.2, 129.7, 129.0, 128.6, 128.3, 127.4, 124.8, 124.4, 123.2, 116.4;

IMINOPHOSPHORANE-MEDIATED EFFICIENT SYNTHESIS
161
MS (EI, m/z,%): 465 (M+ 9), 437 (2), 326 (22), 235 (34), 111 (100), 95 (66), 92 (78), 77
(85); Anal. Calcd. for C22H13ClFN5O2S: C 56.72, H 2.81, N 15.03; Found C 56.84, H 2.94,
N 15.17%.
6-(3-Chlorophenyl)-3,6-dihydro-5-[(p-fluorophenyl)sulfinyl]-3-
phenyl-1,2,3-tri- azolo[4,5-d]pyrimidine-7-one (6c)
White solid; yield 79%; mp: 263–265 ◦C; IR (KBr): ν = 1742 (C O); 1592, 1526,
1222, 744 cm−1; 1H NMR (CDCl3, 400 MHz): δ = 7.21–7.80 (m, 13H, arom-H); 13C NMR
(CDCl3): δ = 165.5 (C O), 165.1, 163.0, 155.1, 146.5, 138.6, 135.8, 135.6, 132.8, 131.1,
129.5, 129.1, 128.4, 127.6, 127.4, 126.8, 123.3, 122.9, 122.8, 120.2, 117.0, 116.7; MS (EI,
m/z,%): 465 (M+ 17), 437 (7), 326 (19), 235 (43), 111 (100), 95 (36), 92 (58), 77 (80);
Anal. Calcd. for C22H13ClFN5O2S: C 56.72, H 2.81, N 15.03; Found C 56.79, H 2.91, N
15.08%.
3-(4-Chlorophenyl)-3,6-dihydro-5-[(p-fluorophenyl)sulfinyl]-6-
phenyl-1,2,3-tri- azolo[4,5-d]pyrimidine-7-one (6d)
White solid; yield 70%; mp: 257–259 ◦C; IR (KBr): ν = 1742 (C O); 1593, 1529,
1214, 736 cm−1; 1H NMR (CDCl3, 400 MHz): δ = 7.11–7.75 (m, 13H, arom-H); MS (EI,
m/z,%): 465 (M+ 12), 437 (5), 326 (13), 235 (23), 111 (100), 95 (61), 92 (79), 77 (75);
Anal. Calcd. for C22H13ClFN5O2S: C 56.72, H 2.81, N 15.03; Found C 56.81, H 2.95, N
15.26%.
3,6-Bis(4-chlorophenyl)-3,6-dihydro-5-[(p-fluorophenyl)
sulfinyl]-1,2,3-triazolo[4,5-d]pyrimidine-7-one (6e)
White solid; yield 77%; mp: 282–284 ◦C; IR (KBr): ν = 1741 (C O); 1591, 1526,
1216, 754 cm−1; 1H NMR (CDCl3, 400 MHz): δ = 7.26–7.84 (m, 12H, arom-H); 13C NMR
(d6-DMSO): δ = 155.8 (C O), 150.5, 149.7, 141.1, 134.8, 134.4, 132.9, 132.3, 131.0,
129.7, 129.2, 129.0, 128.3, 126.8, 124.3, 123.2, 121.6, 120.2, 120.0, 117.8, 116.4, 115.8;
MS (EI, m/z,%): 501/499 (M+ 4/16), 464 (2), 436 (7), 325 (26), 235 (41), 111 (100), 95
(36), 92 (48), 77 (55); Anal. Calcd. for C22H12Cl2FN5O2S: C 52.81, H 2.42, N 14.00;
Found C 52.92, H 2.35, N 14.23%.
3-(4-Chlorophenyl)-6-(3-chlorophenyl)-3,6-dihydro-5-[(p-fluorophenyl)
sulfinyl]- 1,2,3-triazolo[4,5-d]pyrimidine-7-one (6f)
White solid; yield 74%; mp: 259–261 ◦C; IR (KBr): ν = 1741 (C O); 1595, 1523,
1226, 751 cm−1; 1H NMR (CDCl3, 400 MHz): δ = 7.33–7.81 (m, 12H, arom-H); 13C NMR
(d6-DMSO): δ = 156.0 (C O), 154.8, 150.6, 145.9, 134.8, 134.1, 133.1, 132.7, 132.5,
130.7, 130.4, 130.0, 129.7, 129.3, 129.0, 128.8, 128.3, 127.7, 124.8, 124.4, 121.6, 120.0;
MS (EI, m/z,%): 501/499 (M+ 5/9), 464 (6), 436 (3), 325 (12), 235 (27), 111 (100), 95 (42),
92 (58), 77 (72); Anal. Calcd. for C22H12Cl2FN5O2S: C 52.81, H 2.42, N 14.00; Found C
52.93, H 2.49, N 14.15%.
Synthesis of 3,6-diaryl-3,6-dihydro-5-[(p-fluorophenyl)sulfonyl]-
1,2,3-triazolo [4,5-d]pyrimidin-7-ones (7): General Procedure
Compound 5 (27 mmol) and 20 mL of anhydrous acetic acid were poured into a
50mLflask. Thecatalyst, solidNa2WO4 (0.27g, 0.8mmol), wasaddedat roomtemperature.
After mixing 30% H2O2 (6.12 g, 54 mmol) was added dropwise to the reaction mixture.

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◦
The reaction mixture was stirred at 45–50 C for 5 h, the progress of the reaction was
monitored by TLC. After stirring for another 0.5 h at room temperature 3.4g of Na2SO3
dissolved in 60 mL of water was added. The solid formed was filtered and recrystallized
from DMSO/ethanol to give pure compound 7 as a white crystalline solid.
3,6-Dihydro-3,6-diphenyl-5-[(p-fluorophenyl)sulfonyl]-
1,2,3-triazolo[4,5-d]pyri-midine-7-one (7a)
White solid; yield 83%; mp: 275–276 ◦C; IR (KBr): ν = 1742 (C O); 1594, 1526,
1327, 737 cm−1; 1H NMR (d6-DMSO, 400 MHz): δ = 7.28–8.15 (m, 14H, arom-H); 13
C
NMR (d6-DMSO): δ = 165.4 (C O), 165.1, 162.8, 155.1, 146.5, 138.6, 138.4, 135.8,
135.6, 131.1, 131.0, 129.6, 129.4, 129.2, 127.6, 126.8, 122.8, 120.2, 120.1, 116.6, 116.2,
115.8; MS (EI, m/z,%): 447 (M+ 13), 419 (7), 370 (12), 342 (37), 250 (34), 95 (100), 92
(78), 77 (52); Anal. Calcd. for C22H14FN5O3S: C 59.05, H 3.15, N 15.65; Found C 59.21,
H 3.26, N 15.72%.
6-(4-Chlorophenyl)-3,6-dihydro-5-[(p-fluorophenyl)sulfonyl]-
3-phenyl-1,2,3-tri- azolo[4,5-d]pyrimidine-7-one (7b)
White solid; yield 85%; mp: 271–272 ◦C; IR (KBr): ν = 1747 (C O); 1566, 1525,
1334, 739 cm−1; 1H NMR (d6-DMSO, 400 MHz): δ = 7.27–7.76 (m, 13H, arom-H); 13
C
NMR (d6-DMSO): δ = 156.8 (C O), 155.2, 152.4, 150.1, 143.9, 135.8, 135.4, 134.8,
134.6, 133.7, 133.0, 131.7, 131.4, 130.7, 129.8, 129.6, 129.3, 127.0, 124.7, 124.3, 122.0,
118.2; MS (EI, m/z,%): 481 (M+ 18), 446 (9), 418 (5), 342 (27), 250 (64), 111 (100), 95
(68), 92 (51), 77 (75); Anal. Calcd. for C22H13ClFN5O3S: C 54.83, H 2.72, N 14.53; Found
C 54.90, H 2.88, N 14.66%.
6-(3-Chlorophenyl)-3,6-dihydro-5-[(p-fluorophenyl)sulfonyl]-
3-phenyl-1,2,3-tri- azolo[4,5-d]pyrimidine-7-one (7c)
White solid; yield 82%; mp: 266–267 ◦C; IR (KBr): ν = 1741 (C O); 1593, 1524,
1335, 754 cm−1; 1H NMR (CDCl3, 400 MHz): δ = 7.13–8.17 (m, 13H, arom-H); 13C NMR
(d6-DMSO): δ = 155.9 (C O), 155.0, 150.4, 146.4, 140.5, 138.5, 138.3, 135.5, 133.5,
130.4, 129.9, 129.6, 129.3, 129.0, 128.9, 128.2, 124.7, 124.3, 122.0, 120.3, 116.7, 116.4;
MS (EI, m/z,%): 481 (M+ 15), 446 (8), 418 (9), 342 (32), 250 (59), 111 (100), 95 (72),
92 (54), 77 (75); Anal. Calcd. for C22H13ClFN5O3S: C 54.83, H 2.72, N 14.53; Found C
54.90, H 2.89, N 14.70%.
3-(4-Chlorophenyl)-3,6-dihydro-5-[(p-fluorophenyl)sulfonyl]-6-phenyl-
1,2,3-tri- azolo[4,5-d]pyrimidine-7-one (7d)
White solid; yield 75%; mp: 264–265 ◦C; IR (KBr): ν = 1742 (C O); 1592, 1524,
1337, 724 cm−1; 1H NMR (CDCl3, 400 MHz): δ = 7.26–7.78 (m, 13H, arom-H); 13C NMR
(d6-DMSO): δ = 156.0 (C O), 154.7, 149.7, 140.6, 135.5, 134.9, 133.7, 129.7, 129.1,
129.0, 128.9, 128.6, 128.4, 128.1, 126.6, 123.6, 121.9, 120.5, 120.3, 117.6, 116.6, 115.9;
MS (EI, m/z,%): 481 (M+ 28), 446 (3), 418 (6), 342 (37), 250 (54), 111 (100), 95 (78),
92 (58), 77 (45); Anal. Calcd. for C22H13ClFN5O3S: C 54.83, H 2.72, N 14.53; Found C
54.91, H 2.84, N 14.60%.

IMINOPHOSPHORANE-MEDIATED EFFICIENT SYNTHESIS
163
3,6-Bis(4-chlorophenyl)-3,6-dihydro-5-[(p-fluorophenyl)sulfonyl]-
1,2,3-triazolo- [4,5-d]pyrimidine-7-one (7e)
White solid; yield 79%; mp: 273–275 ◦C; IR (KBr): ν = 1739 (C O); 1595, 1526,
1334, 734 cm−1; 1H NMR (CDCl3, 400 MHz): δ = 7.29–7.80 (m, 12H, arom-H); 13C NMR
(d6-DMSO): δ = 155.9 (C O), 154.2, 151.0, 149.1, 142.3, 140.5, 135.0, 134.6, 134.3,
132.8, 131.0, 130.7, 129.7, 129.2, 129.0, 128.8, 128.3, 126.4, 124.3, 123.2, 117.6, 116.4;
MS (EI, m/z,%): 517/515 (M+ 3/12), 480 (6), 404 (3), 376 (17), 250 (34), 111 (100), 95
(48), 92 (54), 77 (61); Anal. Calcd. for C22H12Cl2FN5O3S: C 51.18, H 2.34, N 13.56;
Found C 51.32, H 2.43, N 13.66%.
3-(4-Chlorophenyl)-6-(3-chlorophenyl)-3,6-dihydro-5-[(p-fluorophenyl)
sulfonyl]-1,2,3-triazolo[4,5-d]pyrimidine-7-one (7f)
White solid; yield 75%; mp: 257–259 ◦C; IR (KBr): ν = 1743 (C O); 1591, 1523,
1327, 762 cm−1; 1H NMR (CDCl3, 400 MHz): δ = 7.11–8.26 (m, 12H, arom-H); 13C NMR
(d6-DMSO): δ = 156.5 (C O), 155.1, 151.5, 150.0, 142.5, 141.1, 135.4, 135.1, 134.8,
134.1, 133.3, 133.1, 131.6, 131.4, 130.2, 129.7, 129.5, 129.5, 128.8, 126.9, 124.8, 124.0;
MS (EI, m/z,%): 517/515 (M+ 11/23), 480 (4), 404 (7), 376 (27), 250 (39), 111 (100),
95 (78), 92 (45), 77 (52); Anal. Calcd. for C22H12Cl2FN5O3S: C 51.18, H 2.34, N 13.56;
Found C 51.27, H 2.44, N 13.62%.
REFERENCES
1. Santana, L.; Teijeira, M.; Uriarte, E.; Balzarini, J.; De Clercq, E. Eur. J. Med. Chem. 2002, 37,
755–760.
2. Blanco, J. M.; Caamano, O.; Fernandez, F.; Garcia-Mera, X.; Hergueta, A. R.; Lopez, C.;
Rodriguez-Borges, J. E.; Balzarini, J.; De Clerco, E. Chem. Pharm. Bull. 1999, 47, 1314–1323.
3. Peng, H.; Kumaravel, G.; Yao, G.; Sha, L.; Wang, J.; Vlijmen, H. V.; Bohnert, T.; Huang, C.; Vu,
C. B.; Ensinger, C. L.; Chang, H.; Engber, T. M.; Whalley, E. T.; Petter, R. C. J. Med. Chem.
2004, 47, 6218–6229.
4. Vu, C. B.; Shields, P.; Peng, B.; Kumaravel, G.; Jin, X.; Phadke, D.; Wang, J.; Engber, T.; Ayyub,
E.; Petter, R. C. Bioorg. Med. Chem. Lett. 2004, 14, 4835–4838.
5. Zhang, N.; Kaloustian, S. A.; Nguyen, T.; Afragola, J.; Hernandez, R.; Lucas, J.; Gibbons, J.;
Beyer, C. J. Med. Chem. 2007, 50, 319–327.
6. Kleschich, W. A.; Costales, M. J.; Dunbar, J. E. Pestic. Sci. 1990, 29, 341–355.
7. Gerwick, B. C.; Subramanian, M. V.; Loney-Gallant, V. I.; Chandler, D. P. Pestic. Sci. 1990, 29,
357–364.
8. Bell, B. M.; Fanwick, P. E.; Graupner, P. R.; Roth, G. A. Org. Process Res. Dev. 2006, 10,
1167–1171.
9. Okamura, T.; Kurogi, Y.; Hashimoto, K.; Nishikawa, H.; Nagao, Y. Bioorg. Med. Chem. Lett.
2004, 14, 2443–2446.
10. Loper, B. R.; Cobb, W. T.; Anderson, K. A. J. Agric. Food Chem. 2002, 50, 2601–2606.
11. Girasolo, H. M. A.; Schillaci, D.; Salvo, C. D.; Barone, G.; Silvestri, A.; Ruisi, G. J. Organomet.
Chem. 2006, 691, 693–701.
12. Boer, S. G. J.; Thornburgh, S.; Uptake, R. J. Pest Manag. Sci. 2006, 62, 316–324.
13. Yang, G. F.; Liu, H. Y.; Yang, H. Z. Pestic. Sci. 1999, 55, 1143–1150.
14. Chen, C. N.; Lv, L. L.; Ji, F. Q.; Chen, Q.; Xu, H.; Yang, G. F. Bioorg. Med. Chem. 2009, 17,
3011–3017.
15. Dolbier, W. R. Jr. J. Fluorine Chem. 2005, 126, 157–163.

164
T. WANG ET AL.
16. Kukhar, V. P. J. Fluorine Chem. 1994, 69, 199–205.
17. Welch, J. T. Tetrahedron 1987, 43, 3123–3125.
18. Li, G. Y.; Qian, X. H.; Cui, J. N.; Huang, Q. C.; Cui, D. W. J. Fluorine Chem. 2006, 127, 182–186.
19. Liu, Y. X.; Zhao, Q. Q.; Wang, Q. M.; Li, H.; Huang, R. Q.; Li, Y. H. J. Fluorine Chem. 2005,
126, 345–348.
20. Xua, X. Y.; Qian, X. H.; Lia, Z.; Song, G. H.; Chen, W. D. J. Fluorine Chem. 2006, 127, 297–300.
21. Xua, X. Y.; Qian, X. H.; Li, Z.; Song, G. H.; Chen, W. D. J. Fluorine Chem. 2004, 125, 1159–1162.
22. Zheng, X. M.; Li, Z.; Wang, Y. L.; Chen, W. D.; Huang, Q. C. J. Fluorine Chem. 2003, 123,
163–169.
23. Zhao, J. F.; Xie, C.; Xu, S. Z.; Ding, M. W.; Xiao, W. J. Org. Biomol. Chem. 2006, 4, 130–134.
24. Bonini, C.; Auria, M. D.; Funicello, M.; Romaniello, G. Tetrahedron 2002, 58, 3507–3512.
25. Zhao, M. X.; Wang, M. X.; Yu, C. Y.; Huang, Z. T. J. Org. Chem. 2004, 69, 997–1000.
26. Csampai, A.; Turos, G.; Kudar, V.; Simon, K. Eur. J. Org. Chem. 2004, 4, 717–723.