A Facile one-pot three-component synthesis of 5-(trifluoromethyl)-4,7- dihydro-[1,2,4]-triazolo[1,5-a]pyrimidine derivatives in ionic liquid

Article abstract of DOI:10.1002/cjoc.201180412

An efficient one-pot synthesis of 5-(trifluoromethyl)-4,7-dihydro-7-aryl- [1,2,4]triazolo[1,5-a]pyrimidine derivatives was performed via the reaction of aryl aldehyde, 3-amino-1,2,4-triazole and ethyl 4,4,4-trifluoro-3-oxobutanoate or 4,4,4-trifluoro-1-phenylbutane-1,3-dione in ionic liquid. This method has the advantages of short synthetic route, operational simplicities, mild reaction conditions, high yields and eco-friendliness.

Full text of DOI:10.1002/cjoc.201180412

FULL PAPER
A Facile One-Pot Three-Component Synthesis of
5-(Trifluoromethyl)-4,7-dihydro-[1,2,4]-triazolo[1,5-a]pyrimidine
Derivatives in Ionic Liquid
Li, Tuanjiea(李团结)
Yao, Changsheng*,b(姚昌盛)
Lei, Songa(雷松)
Yu, Chenxiaa(于晨侠)
Tu, Shujianga(屠树江)
a School of Chemistry and Engineering, Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional
Materials, Xuzhou Normal University, Xuzhou, Jiangsu 221116, China
b School of Chemistry and Engineering, Key Laboratory of Biotechnology for Medicial Plant, Xuzhou Normal
University, Xuzhou, Jiangsu 221116, China
An efficient one-pot synthesis of 5-(trifluoromethyl)-4,7-dihydro-7-aryl-[1,2,4]triazolo[1,5-a]pyrimidine de-
rivatives was performed via the reaction of aryl aldehyde, 3-amino-1,2,4-triazole and ethyl 4,4,4-trifluoro-3-
oxobutanoate or 4,4,4-trifluoro-1-phenylbutane-1,3-dione in ionic liquid. This method has the advantages of short
synthetic route, operational simplicities, mild reaction conditions, high yields and eco-friendliness.
Keywords multicomponent reaction, trifluoromethyl, triazolo[1,5-a]pyrimidine, ionic liquid
Introduction
as long reaction time, complicated procedures, low
yields, operational complexity and the narrow applica-
tion scope of substrates. As the consequence, a simple,
rapid, and efficient procedure is still highly desirable for
the synthesis of these important heterocyclic com-
pounds.
Ionic liquids as substitutes for volatile organic sol-
vents are used as green media for various organic trans-
formations because of their unique properties of non-
volatility, nonflammability, recyclability and homoge-
nous media. On the other hand, multi-component reac-
tions (MCRs) as resource- and time-effective and eco-
nomically favorable processes are wildly performed in
the synthesis of heterocyclic compounds.12 Many MCRs
were carried out efficiently in ionic liquids.13 However,
to the best of our knowledge, there is no report on the
preparation of 5-(trifluoromethyl)-4,7-dihydro-7-aryl-
[1,2,4]-triazolo[1,5-a]pyrimidine derivatives by MCRs
in ionic liquids.
As part of our continued interests in the synthesis of
heterocyclic compounds via MCR in ionic liquids,14
herein we report an efficient one-pot three-component
synthesis of 5-(trifluoromethyl)-4,7-dihydro-7-aryl-
[1,2,4]-triazolo[1,5-a]pyrimidine derivatives by treat-
ment of aldehydes with 3-amino-1,2,4-triazole and ethyl
4,4,4-trifluoro-3-oxobutanoate or 4,4,4-trifluoro-1-
phenylbutane-1,3-dion in ionic liquid. This synthetic
reaction is shown in Scheme 1.
Since many 1,2,4-triazolo[1,5-a]pyrimidine deriva-
tives possess biological activities and are used as anti-
cancer agents,1 inhibitors of the MDM2-p53 pro-
tein-protein interaction,2 antituberculosis agents3 and
dehydrogenase inhibitors4 etc., the structural modifica-
tion of these nitrogen-containing heterocyclic scaffolds
is of considerable interest for both organic and medici-
nal chemistry. They were synthesized by reaction of
aldehydes with 3-amino-1,2,4-triazole and ethyl aceto-
acetate or cyclic β-diketones via the Biginelli-like reac-
tion.5-9 The introduction of a trifluoromethyl group into
organic molecules often changes their physical, chemi-
cal, and physiological properties.10 The trifluoromethy-
lation of 1,2,4-triazolo[1,5-a]pyrimidine may provide a
new potential biological compound library for biomedi-
cinal screening. However, only a few studies on the
synthesis of 5-(trifluoromethyl)-4,7-dihydro-[1,2,4]-
triazolo[1,5-a]pyrimidine derivatives have been de-
scribed in the literature. Pryadeina and co-workers11
first reported the synthesis of these derivatives by the
reaction of fluorinated 3-oxo esters with aldehyde and
3-amino-1,2,4-triazole or 2-benzylidene-2-fluoroacyl
esters with 3-amino-1,2,4-triazole. Their procedure un-
derwent two steps and the cyclocondensation reactions
were realized by using ethanol or DMF as solvent and
hydrochloric acid or sulfamic acid as catalyst. Besides,
the present method has some other disadvantages such
*
E-mail: csyao@xznu.edu.cn; Tel.: 0086-0516-83500065; Fax: 0086-0516-83500065
Received April 25, 2011; revised May 20, 2011; accepted July 15, 2011.
Project supported by the National Natural Science Foundation of China (No. 200810102050), the Major Basic Research Project of the Natural
Science Foundation of the Jiangsu Higher Education Institutions (No. 09KJA430003), the Natural Science Foundation of Xuzhou City (No.
XM09B016), Graduate Foundation of Xuzhou Normal University (No. 2010YLB029) and Qing Lan Project (No. 08QLT001).
Chin. J. Chem. 2011, 29, 2427— 2432
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
2427

Li et al.
FULL PAPER
Scheme 1
＋
－
Under the optimal conditions ([bmim ][ BF ], 110
4
℃), a series of 5-(trifluoromethyl)-4,7-dihydro-7-aryl-
[1,2,4]-triazolo[1,5-a]pyrimidine derivatives (Table 3,
4a—4m) were synthesized with good yields via the
one-pot reactions of aryl aldehydes with 3-amino-1,2,4-
triazole and ethyl 4,4,4-trifluoro-3-oxobutanoate. The
results reveal that both electron-rich aryl aldehyde and
electron-deficient aryl aldehyde in the multicomponent
reactions afforded the corresponding products with good
yields efficiently under the same conditions. In order to
expand the scope of this method, the replacement of
ethyl 4,4,4-trifluoro-3-oxobutanoate with 4,4,4-tri-
fluoro-1-phenylbutane-1,3-dione was examined. To our
delight, the reactions proceeded steadily to afford a se-
ries of new triazolopyrimidine compounds 4n—4s (Ta-
ble 3) with good to excellent yields at 80 ℃. Moreover,
the results also show that the electronic nature of sub-
stituents of the aromatic aldehyde had no significant
effect on the reaction in the viewpoint of yields.
H
N
O
O
Ionic Liquid
N
+
+
H2N
ArCHO
F3C
R
N
1
2
3
O
Ar
N
R
N
N
F3C
N
H
4
Results and discussion
In order to choose the optimal solvent, the reaction
of phenyl aldehyde (1 mmol) with 3-amino-1,2,4-tria-
zole (1 mmol), and ethyl 4,4,4-trifluoro-3-oxobu-
tanoate (1 mmol) was examined at 100 ℃ in different
solvents. The results in Table 1 show that the desired
In this study, all of the products were characterized
product＋ 4a was given with higher yield (85%) in
1
－
4
by IR and H NMR spectral data as well as elemental
[bmim ＋ ][ BF ] than other counterparts. Thus,
－
4
analyses. To further elucidate the structure of products,
a single crystal of compound 4k was prepared and its
structure was established by X-ray crystallographic
analysis. The molecular structure of 4k is shown in Fig-
ure 1.
[bmim ][ BF ] was used as solvent for further
optimization of reaction conditions, the same reaction
was carried out at temperature ranging from 80 to 130
℃, with an increment of 10 ℃ each time.
Table 1 Solvent effect on the synthesis of 4aa
Entry
Solvent
Time/h
Yield/%
81
＋
－
1
2
3
4
5
[byp ][ BF
]
－
4
7
7
9
7
8
8
4
＋
[bmim ][ BF
]
85
CH3CN
EtOH
HOAc
DMF
60
70
73
6
64
＋
[byp ][ BF ], 1-butylpyridinium tetrafluoroborate; [bmim＋]•
a
－
4
－
4
[ BF ], 3-butyl-1-methyl-1H-imidazol-3-ium tetrafluoroborate.
As shown in Table 2, the yield of product 4a in-
creased, and the reaction time was shortened with the
temperature increasing from 80 to 110 ℃, while the
yield significantly decreased when the temperature was
further increased to 120 and 130 ℃. Therefore, 110 ℃
was chosen as reaction temperature for all further MCR
reactions in ionic liquid.
Figure 1 The structure of compound 4k.
The recovery and reuse of solvent are highly prefer-
able in terms of green chemistry. Therefore, with the
success of the above reactions, we further studied the
Table 2 Temperature effect on the synthesis of 4a
Entry
Tem./℃
Time/h
Yield/%
73
reuse of the reaction solve＋nt. It turned out that the re-
1
2
3
4
5
6
80
12
10
7
－
covery and reuse of [bmim ][ BF ] is not only conven-
4
90
80
ient but also efficient. Thus, at completion monitored by
TLC, the reaction mixture was cooled to room tempera-
ture, then poured into water. The solid product was col-
lected by filtration and recrystallized from ethanol to
100
110
120
130
85
6
92
5
75
5
70
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© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 2427— 2432

Synthesis of 5-(Trifluoromethyl)-4,7-dihydro-[1,2,4]-triazolo[1,5-a]pyrimidine Derivatives
＋
－
Table 3 Synthesis of 4 in ionic liquid ([bmim ][ BF ])
4
Product No.
Ar
R
Time/h
Yielda/%
m.p./℃
145—146 (Ref 11: 157—159)
180—182
4a
C6H5
OC2H5
OC2H5
OC2H5
OC2H5
OC2H5
OC2H5
OC2H5
OC2H5
OC2H5
OC2H5
OC2H5
OC2H5
OC2H5
C6H5
6
7
6
6
7
7
6
7
7
6
6
6
7
9
8
9
8
9
8
92
4b
2,4-Cl2C6H3
4-NO2C6H4
4-FC6H4
85
4c
87
245—246
4d
85
209—211
4e
3-BrC6H4
86
193—195
4f
4-BrC6H4
88
241—242
4g
3-FC6H4
86
182—184
4h
3-NO2C6H4
2-FC6H4
84
248—249
4i
88
156—157
4j
3,4-(OCH2O)C6H3
2-ClC6H4
87
197—199
4k
86
191—193
4l
3-ClC6H4
85
184—186
4m
2,4-(NO2)2C6H3
4-NO2C6H4
C6H5
85
214—216
4n
85
222—223
4o
C6H5
82
231—233
4p
3,4-(OCH2O)C6H3
3-BrC6H4
C6H5
86
248—249
4q
C6H5
82
222—224
4r
4-FC6H4
C6H5
83
232—234
4s
3-FC6H4
C6H5
84
265—266
a Isolated yields.
give the pure product. The filtrate was washed with ace-
tic ester, concentrated under reduced pressure, and dried
in vacuo at 100 ℃ for several hours to obtain the re-
usable solvent. Studies by using phenyl aldehyde,
3-amino-1,2,4-triazole and ethyl 4,4,4-trifluoro-3-oxo-
butanoate as model substrates show that the recovered
solvent could be successively recycled in subsequent
reactions without remarkable decrease in its efficiency.
The results of the reuse of the ionic liquid are summa-
rized in Table 4. Even in the fourth round, the yield of
the product 4a is fairly high.
Scheme 2
OH
O
O
O
F3C
R
O
- H2O
2
F3C
Ar
R
Ar
H
Ionic Liquid
OH
1
5
Ar
O
R
N
O
O
N
R
F3C
N
N
Ar
N
O
H2N
NH2
CF3
N
H
6
7
3
＋
－
4
Table 4 Study on the reuse of ionic liquid ([bmim ][ BF ])
O
Ar
O
Ar
Round
1
2
3
4
N
N
N
N
- H2O
R
N
R
4a yield/%
92
89
84
78
N
F3C
N
F3C
N
H
H
OH
4
Although the detailed mechanism of the above reac-
tion remains to be fully clarified, the formation of
8
trifluoromethylated 1,2,4-triazolo[1,5-a]pyrimidine
4
5-(trifluoromethyl)-4,7-dihydro-7-aryl-[1,2,4]-triazolo[1,
could be explained by the reaction sequence presented
in Scheme 2.15 Knoevenagel condensation between aryl
aldehyde and trifluoromethylated building block 2 gave
intermediate 6. Michael addition between 6 and 3 then
afforded the intermediate 7, which subsequently under-
went intramolecular cyclization and dehydration to give
the ultimate compounds 4.
5-a]pyrimidine derivatives in ionic liquid medium
＋
－
[bmim ][ BF ]. This protocol has the advantages of
4
short synthetic route, operational simplicities, mild re-
action conditions and high yields. Furthermore, the
ionic liquid was chosen as a kind of green solvent,
which could be reused for several rounds without sig-
nificant loss of activity.
Conclusions
Experimental
In summary, we have developed an efficient and en-
vironmentally benign procedure for synthesizing
All chemicals were purchased from commercial
sources and purified by recrystallization or distillation.
Chin. J. Chem. 2011, 29, 2427— 2432
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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2429

Li et al.
FULL PAPER
Infrared (IR) spectra were recorded on a TENSOR 27
spectrophotometer in KBr pellet and a－re reported in
(br, 1H, NH); IR (KBr) v: 3374, 3220, 3104, 2983, 2814,
2361, 2341, 1723, 1600, 1530, 1509, 1489, 1453, 1418,
1394, 1373, 1350, 1305, 1207, 1184, 1139, 1100, 1072,
1011, 992, 881, 836, 805, 784, 728, 715, 705, 647 cm .
Anal. calcd for C15H12F4N4O2: C 50.57, H 3.39, N 15.73;
found C 50.55, H 3.41, N 15.80.
1
terms of frequency of absorption (cm 1). H NMR
－1
spectra were measured on a Bruker DPX 400 MHz
spectrometer in DMSO-d6 with chemical shift (δ) rela-
tive to TMS as internal standard. Elemental analyses
were determined by using a Perkin-Elmer 240c elemen-
tal analysis instrument. Melting points were determined
in open capillaries and are uncorrected. The single crys-
tal diffraction data were gathered on a Rigaku Saturn
diffractometer.
Compound 4e 1H NMR (DMSO-d6, 400 MHz) δ:
1.00 (t, J＝7.6 Hz, 3H, CH3), 4.00 (q, J＝6.8 Hz, 2H,
CH2), 6.48 (s, 1H, CH), 7.25 (s, 1H, CH), 7.34 (s, 1H,
ArH), 7.54 (d, J＝7.6 Hz, 2H, ArH), 7.82 (s, 1H, ArH),
12.63 (br, 1H, NH); IR (KBr) v: 3220, 3106, 2990, 2877,
2813, 2361, 1719, 1662, 1600, 1559, 1475, 1435, 1418,
1391, 1354, 1300, 1210, 1141, 1103, 1072, 1024, 995,
975, 900, 882－, 847, 803, 778, 727, 715, 695, 682, 653,
642, 618 cm 1. Anal. calcd for C15H12BrF3N4O2: C
43.19, H 2.90, N 13.43; found C 43.22, H 2.85, N 13.35.
Compound 4f 1H NMR (DMSO-d6, 400 MHz) δ:
1.00 (t, J＝7.6 Hz, 3H, CH3), 4.00 (q, J＝6.8 Hz, 2H,
CH2), 6.46 (s, 1H, CH), 6.80 (s, 1H, CH), 7.24 (d, J＝
7.6 Hz, 2H, ArH), 7.59 (d, J＝7.6 Hz, 2H, ArH), 12.54
(br, 1H, NH); IR (KBr) v: 3222, 3110, 2985, 2817, 1721,
1660, 1601, 1561, 1472, 1428, 1417, 1389, 1354, 1301,
1212, 1137, 1099, 1070, 1021, 991, 8－94, 867, 854, 803,
General procedure for the synthesis of benzo[4,5]-
imidazo[1,2-a]pyrimidine derivatives (4a—4x)
Aryl aldehyde 1 (1 mmol), ethyl 4,4,4-trifluoro-
3-oxobutanoate or 4,4,4-trifluoro-1-phenylbutane-1,3-
dione 2 (1 mmol) and 3-amino-1,2,4-triazole 3 (1 mmol)
＋
－
were mixed in 3 mL [bmim ][ BF ]. Then, the mixture
4
was stirred for a certain time (monitored by TLC) at 110
℃ or 80 ℃. The result mixture was cooled to room
temperature and poured into 20 mL of water. The solid
product was collected by filtration and recrystallized
from ethanol to give the pure compound 4. The filtrate
was washed with acetic ester for several times, concen-
trated under reduced pressure, and dried in vacuo at 100
℃ for several hours to give the reusable solvent.
1
762, 721, 716, 703, 682, 649, 642 cm . Anal. calcd for
C15H12BrF3N4O2: C 43.19, H 2.90, N 13.43; found C
43.21, H 2.91, N 13.41.
Compound 4a 1H NMR (DMSO-d6, 400 MHz) δ:
1.00 (t, J＝7.6 Hz, 3H, CH3), 4.00 (q, J＝6.8 Hz, 2H,
CH2), 6.45 (s, 1H, CH), 7.25—7.27 (m, 2H, ArH),
7.32—7.39 (m, 3H, ArH＋CH), 7.79 (s, 1H, ArH),
11.62 (br, 1H, NH); IR (KBr) v: 3218, 3112, 2983, 2869,
1712, 1600, 1458, 1416, 1369, 1305, 1256, 1207, 1180,
1171, 1142, －1115, 1024, 993, 880, 843, 749, 723, 708,
Compound 4g 1H NMR (DMSO-d6, 400 MHz) δ:
1.00 (t, J＝7.6 Hz, 3H, CH3), 4.00 (q, J＝6.8 Hz, 2H,
CH2), 6.49 (s, 1H, CH), 7.09—7.21 (m, 3H, ArH＋CH),
7.40—7.46 (m, 1H, ArH), 7.82 (s, 1H, ArH), 11.69 (br,
1H, NH); IR (KBr) v: 3107, 2987, 2876, 2809, 2361,
1719, 1612, 1559, 1507, 1489, 1453, 1420, 1393, 1370,
1354, 1338, 1305, 1266, 1229, 1201, －1162, 1117, 1097,
1
1
697, 675 cm . Anal. calcd for C15H13F3N4O2: C 53.26,
994, 872, 785, 756, 725, 691, 652 cm . Anal. calcd for
H 3.87, N 16.56; found C 53.20, H 3.76, N 16.63.
C15H12F4N4O2: C 50.57, H 3.39, N 15.73; found C 50.55,
H 3.37, N 15.75.
Compound 4b 1H NMR (DMSO-d6, 400 MHz) δ:
1.00 (t, J＝6.8 Hz, 3H, CH3), 3.94—4.01 (m, 2H, CH2),
6.90 (s, 1H, CH), 7.44—7.49 (m, 2H, ArH), 7.64 (s, 1H,
CH), 7.80 (s, 1H, ArH), 11.74 (br, 1H, NH); IR (KBr) v:
3218, 3107, 2981, 2805, 1712, 1602, 1540, 1475, 1419,
1390, 1368, 1336, 1269, 1201, 1139, 1105, 1007, 991,
Compound 4h 1H NMR (DMSO-d6, 400 MHz) δ:
1.00 (t, J＝7.6 Hz, 3H, CH3), 4.00 (q, J＝6.8 Hz, 2H,
CH2), 6.71 (s, 1H, CH), 6.90 (s, 1H, CH), 7.73 (d, J＝
8.4 Hz, 2H, ArH), 8.24 (d, J＝8.0 Hz, 2H, ArH), 12.72
(s, 1H, NH); IR (KBr) v: 3221, 3101, 3069, 2987, 2876,
2816, 1717, 1614, 1558, 1539, 1477, 1447, 1418, 1353,
1305, 1269, 1163, 1101, 1015, 99－1, 926, 876, 813, 786,
736, 728, 709, 684, 650 cm 1. Anal. calcd for
C15H12F3N5O4: C 47.00, H 3.16, N 18.27; found C 47.04,
H 3.21, N 18.22.
－1
875, 832, 810,785, 721, 715, 682, 641 cm . Anal. calcd
for C15H11Cl2F3N4O2: C 44.25, H 2.72, N 13.76; found
C 44.32, H 2.52, N 13.70.
Compound 4c 1H NMR (DMSO-d6, 400 MHz) δ:
1.00 (t, J＝6.8 Hz, 3H, CH3), 4.00 (q, J＝6.8 Hz, 2H,
CH2), 6.62 (s, 1H, CH), 7.54 (d , J＝8.0 Hz, 2H, ArH),
7.68 (s, 1H, CH), 8.24 (d, J＝8.0 Hz, 2H, ArH), 12.68
(br, 1H, NH); IR (KBr) v: 3218, 3107, 2986, 2873, 2814,
1717, 1600, 1520, 1473, 1453, 1418, 1394, 1352, 1305,
1269, 1207, 1186, 1158, 1142, 1105, 1021, 992, 873,
Compound 4i 1H NMR (DMSO-d6, 400 MHz) δ:
1.00 (t, J＝7.6 Hz, 3H, CH3), 4.00 (q, J＝6.8 Hz, 2H,
CH2), 6.68 (s, 1H, CH), 7.18—7.23 (m, 2H, ArH),
7.36—7.43 (m, 2H, ArH), 7.80 (s, 1H, CH), 11.55 (br,
1H, NH); IR (KBr) v: 3109, 2983, 2869, 2803, 1733,
1601, 1552, 1507, 1490, 1418, 1380, 1352, 1338, 1305,
1245, 1210, 1201, 1158, 1040, 997,－944, 928, 879, 823,
－1
851, 822, 800, 727,715, 695, 675, 646 cm . Anal. calcd
for C15H12F3N5O4: C 47.00, H 3.16, N 18.27; found C
47.12, H 3.06, N 18.30.
1
800, 779, 726, 707, 655, 636 cm . Anal. calcd for
Compound 4d 1H NMR (DMSO-d6, 400 MHz) δ:
1.00 (t, J＝6.8 Hz, 3H, CH3), 4.00 (q, J＝6.8 Hz, 2H,
CH2), 6.49 (s, 1H, CH), 6.85 (s, 1H, CH), 7.05 (d, J＝
7.6 Hz, 2H, ArH), 7.32 (d, J＝7.6 Hz, 2H, ArH), 12.68
C15H12F4N4O2: C 50.57, H 3.39, N 15.73; found C 50.53,
H 3.42, N 15.68.
Compound 4j 1H NMR (DMSO-d6, 400 MHz) δ:
1.00 (t, J＝7.2 Hz, 3H, CH3), 4.00 (q, J＝6.8 Hz, 2H,
2430
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© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 2427— 2432

Synthesis of 5-(Trifluoromethyl)-4,7-dihydro-[1,2,4]-triazolo[1,5-a]pyrimidine Derivatives
CH2), 6.02 (s, 2H, CH2), 6.37 (s, 1H, CH), 6.74 (d, J＝
8.0 Hz, 1H, ArH), 6.79 (s, 1H, ArH), 6.88 (d, J＝8.0 Hz,
1H, ArH), 7.79 (s, 1H, ArH), 11.55 (br, 1H, NH); IR
(KBr) v: 3217, 3107, 2985, 2903, 2360, 1867, 1717,
1607, 1547, 1510, 1490, 1418, 1380, 1352, 1338, 1245,
1230, 1196, 1158, 1040, 997, 944, 928, 879, 823, 800,
779, 726, 707, 655, 636 cm － 1. Anal. calcd for
C16H13F3N4O4: C 50.27, H 3.43, N 14.66; found 50.31,
H 3.40, N 14.71.
H 3.55, N 15.17.
Compound 4p 1H NMR (DMSO-d6, 400 MHz) δ:
5.96 (d, J＝7.2 Hz, 2H, OCH2O), 6.33 (s, 1H, CH), 6.53
(dd, J1＝6.4, 1.6 Hz, 1H, ArH), 6.65 (d, J＝1.6 Hz, 1H,
ArH), 6.75 (d, J＝8.0 Hz, 1H, ArH), 7.47 (t, J＝8.0 Hz,
2H, ArH), 7.63 (t, J＝7.2 Hz, 1H, ArH), 7.77 (s, 1H,
CH), 7.80 (d, J＝8.0 Hz, 2H, ArH), 11.45 (br, 1H, NH);
IR (KBr) v: 3105, 3038, 2979, 2869, 2789, 1651, 1604,
1561, 1504, 1449, 1417, 1385, 1349, 1319, 1281, 1247,
1204, 1181, －1102, 1041, 931, 805, 791, 753, 726, 701,
Compound 4k 1H NMR (DMSO-d6, 400 MHz) δ:
1.00 (t, J＝7.6 Hz, 3H, CH3), 4.00 (q, J＝6.8 Hz, 2H,
CH2), 6.83 (s, 1H, CH), 7.37—7.47 (m, 4H, ArH), 7.78
(s, 1H, ArH), 11.62 (br, 1H, NH); IR (KBr) v: 3110,
2987, 2872, 2801, 2361, 1985, 1938, 1721, 1602, 1542,
1509, 1485, 1453, 1420, 1389, 1352, 1338, 1294, 1266,
1219, 1201, 1187, 1094, －1008, 993, 886, 864, 821, 762,
1
687, 638 cm . Anal. calcd for C20H13F3N4O3: C 57.98,
H 3.16, N 13.52; found C 57.94, H 3.20, N 13.55.
Compound 4q 1H NMR (DMSO-d6, 400 MHz) δ:
6.48 (s, 1H, CH), 7.11 (d, J＝8.0 Hz, 1H, ArH), 7.24 (t,
J＝8.0 Hz, 1H, ArH), 7.30 (s, 1H, CH), 7.44—7.50 (m,
3H, ArH), 7.66 (t, J＝7.2 Hz, 1H, ArH), 7.80 (t, J＝3.6
Hz, 3H, ArH), 11.42 (br, 1H, NH); IR (KBr) v: 3110,
3053, 2989, 2870, 2812, 2350, 1667, 1614, 1559, 1470,
1451, 1438, 1420, 1355, 1316, 1296, 1268, 1247, 1202,
1179, 1137, 1108, 1070, 1027, 997,－923, 867, 788, 738,
1
725, 701, 678, 644 cm . Anal. calcd for C15H12Cl-
F3N4O2: C 48.34, H 3.25, Cl 9.51, N 15.03; found C
48.35, H 3.24, Cl 9.50, N 15.10.
Compound 4l 1H NMR (400 MHz, DMSO-d6) δ:
1.00 (t, J＝7.6 Hz, 3H, CH3), 4.00 (q, J＝6.8 Hz, 2H,
CH2), 6.50 (s, 1H, CH), 7.21—7.23 (m, 1H, ArH),
7.38—7.42 (m, 3H, ArH), 7.83 (s, 1H, ArH), 11.72 (br,
1H, NH); IR (KBr) v: 3220, 3107, 2983, 2875, 1723,
1616, 1562, 1501, 1477, 1419, 138, 1365, 1354, 1342,
1299, 1256, 1232, 1201, 1166, 1098, 1015, 993, 972,
1
725, 691, 669, 645, 625, 599 cm . Anal. calcd for
C19H12BrF3N4O: C 50.80, H 2.69, N 12.47; found C
50.77, H 2.71, N 12.50.
Compound 4r 1H NMR (DMSO-d6, 400 MHz) δ:
6.46 (s, 1H, CH), 7.07—7.16 (m, 4H, ArH), 7.48 (t, J＝
7.6 Hz, 2H, ArH), 7.65 (t, J＝7.6 Hz, 1H, ArH), 7.76 (s,
1H, CH), 7.78 (s, 2H, ArH), 11.47 (br, 1H, NH); IR
(KBr) v: 3045, 2986, 2870, 2811, 1672, 1605, 1560,
1511, 1450, 1421, 1353, 1315, 1305, 1272, 1247, 1226,
1207, 1189, 1177, 1144, 11－12, 1000, 914, 856, 809, 793,
－1
890, 874, 801, 775, 713, 690, 651 cm . Anal. calcd for
C15H12ClF3N4O2: C 48.34, H 3.25, Cl 9.51, N 15.03;
found C 48.37, H 3.21, Cl 9.48, N 15.07.
Compound 4m 1H NMR (DMSO-d6, 400 MHz) δ:
1.00 (t, J＝7.6 Hz, 3H, CH3), 3.97—4.01 (m, 2H, CH2),
7.25 (s, 1H, CH), 7.83 (d, J＝8.4 Hz, 1H, CH), 7.90 (s,
1H, ArH), 8.52 (dd, J1＝8.4, 2.4 Hz, 1H, ArH), 8.74 (d,
J＝2.0 Hz, 1H, ArH), 12.17 (br, 1H, NH); IR (KBr) v:
3205, 3099, 2987, 2871, 1702, 1611, 1530, 1510, 1475,
1413, 1392, 1357, 1334, 1310, 1256, 1228, 1201, 1184,
1094, 994, 870, 837, 821, 797, 779, 743, 734, 725, 705,
1
749, 725, 688, 637, 615 cm . Anal. calcd for C19H12F4-
N4O: C 58.77, H 3.11, N, 14.43; found C 58.74, H 3.13,
N 14.40.
Compound 4s 1H NMR (DMSO-d6, 400 MHz) δ:
6.48 (s, 1H, CH), 6.92—6.97 (m, 2H, ArH), 7.07—7.11
(m, 1H, ArH), 7.29—7.34 (m, 1H, ArH), 7.48 (t, J＝8.0
Hz, 2H, ArH), 7.62—7.68 (m, 1H, Ar), 7.78 (d, J＝1.2
Hz, 1H, CH), 7.80 (s, 2H, ArH), 11.49 (br, 1H, NH); IR
(KBr) v: 3224, 3104, 3044, 2985, 2793, 2348, 1653,
1614, 1561, 1488, 1452, 1420, 1356, 1279, 1230, 1184,
1150, 1121, 1075, 1030, 995, 947, 925, 905, 858, 814,
－1
653, 636 cm . Anal. calcd for C15H11F3N6O6: C 42.07,
H 2.59, N 19.62; found C 42.09, H 2.61, N 19.59.
Compound 4n 1H NMR (DMSO-d6, 400 MHz) δ:
6.66 (s, 1H, CH), 7.40 (d, J＝8.0 Hz, 2H, ArH), 7.50 (t,
J＝8.0 Hz, 2H, ArH), 7.66 (s, 1H, CH), 7.82 (d, J＝7.0
Hz, 3H, ArH), 8.15 (d, J＝8.0 Hz, 2H, ArH), 11.57 (br,
1H, NH); IR (KBr) v: 3108, 3041, 2985, 2867, 2807,
1652, 1559, 1524, 1450, 1428, 1414, 1351, 1319, 1277,
1208, 1147, 1074, 1002, 992, 859, 837, 812, 764, 739,
－1
789, 761, 745, 726, 690, 649, 638, 627, 597 cm . Anal.
calcd for C19H12F4N4O: C 58.77, H 3.11, N 14.43; found
C 58.75, H 3.10, N 14.44.
－1
Crystallographic data
727, 694, 627, 597 cm . Anal. calcd for C19H12F3N5O3:
C 54.95, H 2.91, N 16.86; found C 54.93, H 2.31, N
16.88.
The single-crystal growth was carried out in ethanol
at room temperature. X-ray crystallographic analysis
was was performed using a Rigaku Saturn diffractome-
ter. Crystal data for 4k: C15H12ClF3N4O2, crystal dimen-
sion 0.26 nm×0.22 nm×0.20 mm, monoclinic, space
group P121/n1, a＝9.8927(12) Å, b＝6.8055(6), c＝
24.403(3) Å, β＝92.166 (6)°, V＝1621.6(3) Å3, Mr＝
372.74, Z＝4, Dc＝1.527 g/cm3, λ＝0.71070 Å, μ(Mo
Compound 4o 1H NMR (DMSO-d6, 400 MHz) δ:
6.41 (s, 1H, CH), 7.05 (d, J＝8.0 Hz, 2H, ArH), 7.27 (m,
3H, ArH), 7.46 (t, J＝8.0 Hz, 2H, ArH), 7.64 (s, 1H,
CH), 7.78 (t, J＝8.0 Hz, 3H, ArH), 11.42 (s, 1H, NH);
IR (KBr) v: 3103, 2978, 2863, 2803, 1650, 1602, 1561,
1490, 1449, 1419, 1350, 1320, 1309, 1281, 1243, 1203,
1178, 1146, 1121, 1074, 1015, 1003－, 992, 920, 884, 820,
－ 1
1
Kα)＝0.285 mm , F(000)＝760, S＝1.081, R1 ＝
803, 753, 726, 699, 686, 623 cm . Anal. calcd for
0.0467, wR2＝0.1208.
C19H13F3N4O: C 61.62, H 3.54, N 15.13; found C 61.59,
Chin. J. Chem. 2011, 29, 2427— 2432
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
2431

Li et al.
FULL PAPER
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(E1104251 Zhao, X.; Fan, Y.)
2432
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Chin. J. Chem. 2011, 29, 2427— 2432