Microwave irradiation for accelerating synthesis of 5,6-diphenylimidazo[1, 2-a]pyrimidines based on isoflavones

Article abstract of DOI:10.1080/00397911.2010.516411

Microwave irradiation was used to accelerate the cyclocondensation of isoflavones with 2-aminoimidazole to synthesize 5,6-diphenylimidazo[1,2-a] pyrimidines. A series of 17 new compounds were characterized by Fourier transform infrared, NMR, and elemental

Full text of DOI:10.1080/00397911.2010.516411

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Microwave Irradiation for Accelerating
Synthesis of 5,6-Diphenylimidazo[1,2-
a]pyrimidines Based on Isoflavones
Wen-Yong Han a , Zun-Ting Zhang a , Li Qiu a & Gang Li a
a Key Laboratory of the Ministry of Education for Medicinal
Resources and Natural Pharmaceutical Chemistry, National
Engineering Laboratory for Resource Development of Endangered
Crude Drugs in Northwest of China, and School of Chemistry and
Materials Science, Shaanxi Normal University, Xi'an, China
Version of record first published: 22 Aug 2011.
To cite this article: Wen-Yong Han, Zun-Ting Zhang, Li Qiu & Gang Li (2011): Microwave Irradiation
for Accelerating Synthesis of 5,6-Diphenylimidazo[1,2-a]pyrimidines Based on Isoflavones, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
41:24, 3590-3599
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Synthetic Communications1, 41: 3590–3599, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.516411
MICROWAVE IRRADIATION FOR ACCELERATING
SYNTHESIS OF 5,6-DIPHENYLIMIDAZO[1,2-
a]PYRIMIDINES BASED ON ISOFLAVONES
Wen-Yong Han, Zun-Ting Zhang, Li Qiu, and Gang Li
Key Laboratory of the Ministry of Education for Medicinal Resources and
Natural Pharmaceutical Chemistry, National Engineering Laboratory for
Resource Development of Endangered Crude Drugs in Northwest of China,
and School of Chemistry and Materials Science, Shaanxi Normal University,
Xi’an, China
GRAPHICAL ABSTRACT
Abstract Microwave irradiation was used to accelerate the cyclocondensation of isoflavones
with 2-aminoimidazole to synthesize 5,6-diphenylimidazo[1,2-a]pyrimidines. A series of 17
new compounds were characterized by Fourier transform infrared, NMR, and elemental
analysis. 5-(2-Hydroxyl-4-isopropoxyphenyl)-6-phenylimidazo-[1,2-a]pyrimidine was
determined by x-ray diffraction. A variety of substrates can participate in the process with
good yields and purities, making this methodology suitable for library synthesis in drug
discovery.
Keywords Cyclocondensation; imidazo[1,2-a]pyrimidine;
irradiation
isoflavone; microwave
INTRODUCTION
The importance of the imidazo[1,2-a]pyrimidine nucleus has been well
established in pharmaceutical chemistry on account of its pharmacological activities
as antiviral,[1] anti-inflammatory,[2] antibacterial,[3] and antiarrhythmic drugs.[4]
Chemical modifications of the imidazopyrimidine ring, such as the introduction of
different substituents, have allowed expansion of the research on the structure–
activity relationship to afford new insight into the molecular interaction at the
Received January 21, 2010.
Address correspondence to Zun-Ting Zhang, Key Laboratory of the Ministry of Education for
Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for
Resource Development of Endangered Crude Drugs in Northwest of China, and School of Chemistry
and Materials Science, Shaanxi Normal University, Xi’an 710062, China. E-mail: zhangzt@snnu.edu.cn
3590

5,6-DIPHENYLIMIDAZO[1,2-a]PYRIMIDINE
3591
receptor level, revealing new information such as that imidazo[1,2-a]pyrimidines are
GABAA receptor benzodiazepine binding site ligands that can exhibit functional sel-
ectivity for the a 3 subtype over the a1 subtype.[5] Because of the range of biological
activity they exhibited, these compounds have distinguished themselves as hetero-
cycles of profound chemical and biological significance. Thus, the synthesis of these
molecules attracted our interest. The existing methods for building up the imi-
dazo[1,2-a] pyrimidine parent nucleus involve condensation of 2-aminobenzimida-
zole with acetylene esters,[6] enamino esters,[7] 1,3-diketone,[4] and a,b-unsaturated
ketones.[8] It was reported that the chromone fragment present in isoflavones can
generate a 1,3-diketone equivalent that readily react with amidines[9] and
guanidine[10] to form the corresponding 2-substituted pyrimidines. In the previous
work from our laboratory, we reported the synthesis of a number of 3,4-diarylpyr-
azoles and 4,5-diphenyl-2-pyrimidinylguanidines by using a one-pot reaction of
hydrazine[11] or bisguanidine[12] with isoflavones by conventional methods. We were
interested in the use of microwave irradiation in organic synthesis, because its use
can provide improvements in environmental and economical aspects.[13–15] More-
over, speculation about the influence of microwaves on reaction rates have been
Table 1. Synthesis of 5,6-diphenylimidazo[1,2-a]pyrimidine by cyclocondensation of various isoflavones
with 2-aminoimidazole slulfate in DMSO
Time
(min)
Yield
(%)a
Entry
Substrate
R1
R2
R3
R4
R5
R6
R7
1
2
1a
1b
1c
1d
1e
1f
H
H
H
H
H
H
H
Br
H
H
H
H
H
H
H
H
H
OiPr
OMe
OMe
OMe
OMe
OEt
OMe
OiPr
OBn
OMe
OMe
OH
H
H
H
H
H
H
H
H
H
H
H
H
iPr
H
H
H
H
iPr
H
H
H
30
35
30
35
35
30
30
35
35
40
40
45
50
55
55
55
70
70
63
72
67
76
69
65
75
66
56
58
52
49
40
42
45
29
H
H
H
H
3
H
H
OMe
OMe
OMe
OMe
H
H
4
H
OMe
OMe
H
H
5
OMe
H
H
6
H
7
1g
1h
1i
H
Me
H
H
8
H
H
H
9
H
H
OMe
OH
OH
OMe
H
H
10
11
12
13
14
15
16
17
1j
H
H
H
1k
1l
H
H
iPr
H
H
H
1m
1n
1o
1p
1q
OH
OH
H
H
H
H
H
OH
OH
OH
OH
H
OH
OH
H
H
NO2
iPr
H
H
H
OH
OH
H
aIsolated yield after silica chromatography.

3592
W.-Y. HAN ET AL.
reported whereby the reaction could proceed faster than that under conventional
conditions at the same temperature.[16–18] To the best of our knowledge, using isofla-
vone as a starting material to synthesize the fused heterocycle has not been reported
so far. Herein, we report a new strategy for the preparation of the unknown class of
5,6-diphenylimidazo[1,2-a]pyrimidine by the cyclocondensation of isoflavones (1)
with 2-aminoimi-dazole (2) (Table 1) under microwave irradiation.
RESULTS AND DISCUSSION
We turned our attention to optimize the condition of the cyclocondensations of
isoflavones (1) with 2-aminoimidazole (2) and designed a process by the cyclo-
condensation of ipriflavone (1a) with 2-aminoimidazole sulfate (2) as a model sub-
strate (Table 2). As shown in Table 2, we used NaOH as base, and solvents MeOH,
EtOH, n-BuOH, glycol, and dimethylsulfoxide (DMSO) were attempted. DMSO
gave expected result (Table 2, entry 5). A comparative reactivity study of bases in
the reaction showed that NaOH proved to be the most effective for this cycloconden-
sation (Table 2, entry 5). Further study with varying NaOH equivalents revealed that
Table 2. Optimization of cyclocondensation of ipriflavone 1a with 2-aminoimidazole sulfate 2a
Entry
Solvent
Base
Molar ratios 1a=2=base
Yield (%)b 3a
1
2
MeOH
EtOH
NaOH
NaOH
NaOH
NaOH
NaOH
K2CO3
NaOMe
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
1:1:2
1:1:2
1:1:2
1:1:2
1:1:2
1:1:2
1:1:2
1:1:3
1:1:4
1:1:5
1:2:4
1:3:4
1:4:4
NRc
NRc
18
3
n-BuOH
glycol
4
25
32
5
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
6
19
22
7
8
39
46
9
10
11
12
13
42
58
70
67
aAll reactions were carried out in the appropriate solvent (8 mL) using ipriflavone (1a, 1 mmol), 2-ami-
noimidazole sulfate (2), and base until complete disappearance of 1a (microwave irradiation for 0.5 h,
MeOH, EtOH at boiling point and n-BuOH, glycol, and DMSO at 100 ꢀC, output 240 W, TLC check).
bIsolated yield after silica chromatography.
cNo reaction.

5,6-DIPHENYLIMIDAZO[1,2-a]PYRIMIDINE
3593
4.0 equiv of base is necessary to obtain a good yield of the condensation product
(Table 2, entry 9). Finally, the ratio of 1a and 2 was also evaluated. Using the ratio
of 1a=2 (1:3), we obtained a high yield of 3a for the cyclocondensation reaction
(Table 2, entry 12).
With the optimized reaction conditions and proven results in hand, the
condensation of a variety of structurally divergent isoflavones (1) and 2-aminoimida-
zole (2) were studied to illustrate this concise and general method for the synthesis of
5,6-diphenylimidazo[1,2-a]pyrimidine. All substrates smoothly reacted to give the
corresponding 5,6-diphenylimidazo[1,2-a]pyrimidine in 30–70 min in moderate to
good yields, and the results were summarized in Table 1. All products were charac-
terized by infrared (IR), 1H NMR, 13C NMR, and elemental analysis. Single-crystal
x-ray diffraction analysis of 3a (Fig. 1) was used to corroborate the postulated
structures unequivocally, which added evidence for the structure.
In general, isoflavone 1 substituted with alkoxy and benzyoxyl groups gave
goods yields. In contrast, the presence of the hydroxyl groups gave lower yields.
As shown in Table 1, isoflavones 1a–i (Table 1, entries 1–9), which do not contain
hydroxyl groups, gave yields 3 of about 70%. Isoflavone with one hydroxyl group,
1j–m (Table 3, entries 10–13), gave yields of 3 of only about 55%, whereas those with
two free hydroxyls, 1n–p (Table 3, entries 14–16), gave yields of roughly 40%. Gen-
istein (40,5,7-trihydroxyisoflavone), 1q (Table 3, entry 17), was even more difficult to
condensate, and the yield of 3q was only 29%. The yields of 3 are directly dependent
on the number of free hydroxyl group present on the engaged isoflavone. Because the
hydroxyls of isoflavone 1 under the base condition would be oxygenions, which
possess stronger electron-donating abilities than alkoxy and benzyoxyl groups of
the isoflavone, they prevent condensation of the reaction.
To explain the mechanism for the formation of 5,6-diphenylimidazo[1,2-
a]pyrimidine (3) by the cyclocondensation of isoflavones (1) with 2-aminoimidazole
(2) in the presence of NaOH, a postulated reaction course is illustrated in Scheme 1.
It was reported that isoflavone may undergo a ring-opening reaction when refluxing
in the presence of alkali to form a b-diketone intermediate 4.[19] Subsequent attack of
the primary amine group from the 2-aminoimidazole (2) on the aldehyde carbon in 4,
followed by a ring-closure reaction between the secondary amine and the carbonyl
Figure 1. Unit of asymmetry of 3a. Hydrogen atoms were omitted for clarity.

3594
W.-Y. HAN ET AL.
Scheme 1. Proposed mechanism for the formation of 3.
carbon, produced 3. Meanwhile, the intermediate 4 at high concentration of base
may eliminate HCOOH to generate by-product 5.[19]
CONCLUSION
In summary, we have developed a simple, efficient, one-step method for the
synthesis of functionalized 5,6-diphenylimidazo[1,2-a]pyrimidine by the cyclocon-
densations of isoflavones with 2-aminoimidazole under microwave irradiation con-
ditions. These compounds present a privileged core from a biological point of
view. Also, we report here for the first time that reaction of an aminoimidazole with
isoflavones in the presence of a base affords the fused 5,6-diphenylimidazo[1,2-
a]pyrimidine. Efforts to expand the scope of the method in combination with its
application to the synthesis of pharmaceutical molecules are ongoing in our
laboratory.
EXPERIMENTAL
All other commercially obtained reagents were used as received without further
purification, including 2-aminoimidazole slulfate, ipriflavone, daiazein, genistein,
formonone, and 5-methyl-7-methoxylisoflavone. Substrates 1b, 1h, and 1m were
derived from ipriflavone. Substrates 1c, 1j, 1k, 1o, and 1p were derived from daia-
zein. Substrate 1d was derived from genistein. Substrate 1f and 1i were derived from
formonone. Substrate 1e derived from irisolidone (40,6-dialkoxy-5,7-dihydroxy-
isoflavone) was separated from the flower of pueraria lobata by our group. The
microwave-assisted reactions were performed using a MCR-3 microwave oven
quipped with a Teflon Resin plus temperature probe as sensor. Melting points were
measured on X-5 micromelting-point apparatus and were uncorrected. IR spectra
1
were recorded on a Fourier transform (FT)–IR spectrometer using KBr pellets. H
and 13C NMR spectra were recorded on a Bruker DRX-300 Avance spectrometer
at 300.00 MHz in dimethylsulfoxide (DMSO-d6) with tetramethylsilane (TMS) as
internal standard. The elemental analyses were performed with an Elementar Analy-
sensyteme GmbH Vario EL III instrument. X-ray crystallography dates were given
by a Bruker Smart-1000 CCD diffactometer.

5,6-DIPHENYLIMIDAZO[1,2-a]PYRIMIDINE
3595
General Procedure for the Condensation Reaction
The corresponding isoflavones 1 (1 mmol), 2-aminoimidazole sulfate (2,
3 mmol), sodium hydroxide (4, 5, 6, and 7 mmol were used for 0, 1, 2, and 3 free
hydroxyls, of 1, respectively), and water (1.0 mL) were mixed in DMSO (8 mL) under
microwave irradiation (output 240 W, 100 ꢀC) for 30–70 min. All reactions were
monitored by thin-layer chromatography (TLC), which showed the disappearance
of 1 that was indicative of the reaction being complete. The mixture was added to
water (30 mL) and adjusted to neutrality with a solution of 5% HCl. A precipitate
appeared and was filtered. The precipitate was dissolved in a solution of 10% HCl
(20 mL) and filtered. The mother liquid was neutralized with sodium hydroxide until
the crude product was completely precipitated. The crude product was filtered and
purified by column chromatography on silica gel using chloroform–methanol to give
the corresponding pure product.
Data for Compounds 3a–3q
5-(2-Hydroxyl-4-isopropoxyphenyl)-6-phenylimidazo[1,2-a]pyrimidine
(3a). White solid, mp 207.6–208.5 ꢀC. IR (KBr), n (cmꢁ1): 3435, 2979, 2931, 2579,
1
1612, 1487, 1178, 1119, 1110, 993, 702. H NMR (300 MHz, DMSO-d6), d (ppm):
1.26 (d, J ¼ 5.9 Hz, 6H), 4.51–4.59 (m, 1H), 6.37 (dd, J1 ¼ 8.5 Hz, J2 ¼ 1.7 Hz, 1H),
6.52 (d, 1H), 6.91 (d, J ¼ 8.5 Hz, 1H), 7.28–7.35 (m, 6H), 7.71 (s, 1H), 8.62 (s,
1H), 10.15 (s, 1H). 13C NMR (75 MHz, DMSO-d6), d (ppm): 21.6, 69.6, 102.7,
107.0, 110.0, 111.0, 122.4, 127.6, 128.3, 129.3, 131.4, 134.3, 134.9, 141.6, 147.5,
151.3, 156.5, 160.2. Anal. calcd. for C21H19N3O2: C, 73.03; H, 5.54; N, 12.17. Found:
C, 72.86; H, 5.79; N, 12.28.
5-(2-Hydroxyl-4-methoxyphenyl)-6-phenylimidazo[1,2-a]pyrimidine (3b).
White solid, mp 243.6–244.8 ꢀC. IR (KBr), n (cmꢁ1): 3493, 2961, 2931, 1613, 1492,
1437, 1206, 1033, 706. 1H NMR (300 MHz, DMSO-d6), d (ppm): 3.69 (s, 3H),
6.36 (d, J ¼ 8.4 Hz, 1H), 6.52 (s, 1H), 6.87 (d, J ¼ 8.6 Hz, 1H), 7.16–7.27 (m, 6H),
7.67 (s, 1H), 8.58 (s, 1H), 10.22 (s, 1H). 13C NMR (75 MHz, DMSO-d6), d (ppm):
55.6, 101.9, 106.1, 111.0, 111.3, 122.7, 127.9, 128.8, 129.8, 132.0, 135.0, 135.6,
141.9, 148.2, 151.6, 157.3, 162.4. Anal. calcd. for C19H15N3O2: C, 71.91; H, 4.76;
N, 13.24. Found: C, 71.72; H, 4.93; N, 13.45.
5-(2-Hydroxyl-4-methoxyphenyl)-6-(4-methoxyphenyl)imidazo[1,2-a]-
pyrimidine (3c). White solid, mp 176.6–177.5 ꢀC. IR (KBr), n (cmꢁ1): 3436, 2936,
2834, 2567, 1612, 1495, 1432, 1295, 1238, 1174, 1129, 1033, 976, 810, 745; H NMR
1
(300 MHz, DMSO-d6), d (ppm): 3.74 (s, 6H), 6.42 (d, J ¼ 8.2 Hz, 1H), 6.55 (s, 1H),
6.88 (d, J ¼ 7.6 Hz, 2H), 6.95 (d, J ¼ 8.2 Hz, 1H), 7.19 (d, J ¼ 8.0 Hz, 3H), 7.69 (s,
1H), 8.59 (s, 1H), 10.09 (s, 1H). 13C NMR (75 MHz, DMSO-d6), d (ppm): 55.1,
101.6, 105.7, 110.6, 110.7, 113.8, 121.9, 127.3, 130.5, 131.4, 134.4, 141.0, 147.7,
151.2, 156.7, 158.6, 161.8. Anal. calcd. for C20H17N3O3: C, 69.15; H, 4.93; N,
12.10. Found: C, 69.37; H, 4.79; N, 11.88.
5-(2-Hydroxyl-4,6-dimethoxyphenyl)-6-(4-methoxyphenyl)imidazo[1,2-
a]pyrimidine (3d). White solid, mp 149.7–150.9 ꢀC. IR (KBr), n (cmꢁ1): 3003,
2936, 2839, 2567, 1612, 1494, 1248, 1107, 1030, 828, 560; 1H NMR (300 MHz,

3596
W.-Y. HAN ET AL.
DMSO-d6), d (ppm): 3.51 (s, 3H), 3.71 (s, 3H), 3.73 (s, 3H), 6.15 (s, 2H), 6.87 (d,
J ¼ 8.0 Hz, 2H), 7.20 (d, 3H), 7.66 (s, 1H), 8.56 (s, 1H), 10.07 (s, 1H). 13C NMR
(75 MHz, DMSO-d6), d (ppm): 55.5, 55.6, 55.9, 90.8, 94.3 100.4, 110.9, 114.1,
114.2, 123.7, 128.2, 130.2, 134.8, 138.8, 148.3, 151.4, 157.4, 159.2, 163.2. Anal. calcd.
for C21H19N3O4: C, 66.83; H, 5.07; N, 11.13. Found: C, 66.97; H, 5.21; N, 10.93.
5-(2-Hydroxyl-4,5,6-trimethoxyphenyl)-6-(4-methoxyphenyl)imidazo[1,2-
a]pyrimidine (3e). Yellow solid, mp 153.2–154.6 ꢀC. IR (KBr), n (cmꢁ1): 3235,
2938, 1608, 1499, 1463, 1413, 1247, 1105, 1034, 831, 561; 1H NMR (300 MHz,
DMSO-d6), d (ppm): 3.33 (s, 3H), 3.54 (s, 3H), 3.67 (s, 3H), 3.73 (s, 3H), 6.33 (s,
1H), 6.84 (d, J ¼ 8.0 Hz, 2H), 7.19–7.21 (t, 3H), 7.63 (s, 1H), 8.56 (s, 1H), 9.86 (s,
1H). 13C NMR (75 MHz, DMSO-d6), d (ppm): 55.6, 56.1, 60.9, 61.0, 96.1, 104.2,
111.0, 114.0, 114.3, 123.3, 127.9, 130.4, 134.9, 138.3, 148.3, 151.4, 151.5, 152.2,
156.1, 159.3. Anal. calcd. for C22H21N3O5: C, 64.86; H, 5.20; N, 10.31. Found: C,
64.98; H, 5.45; N, 10.12.
5-(2-Hydroxyl-4-ethoxyphenyl)-6-(4-methoxyphenyl)imidazo[1,2-a]pyri-
midine (3f). Yellow solid, mp 199.4–201.5 ꢀC. IR (KBr), n (cmꢁ1): 3410, 2930, 1607,
1
1489, 1252, 1187, 1036, 831, 466; H NMR (300 MHz, DMSO-d6), d (ppm): 1.32 (s,
3H), 3.73 (s, 3H), 3.99 (d, J ¼ 5.9 Hz, 2H), 6.40 (d, J ¼ 6.8 Hz, 1H), 6.55 (s, 1H),
6.88–6.94 (t, 3H), 7.20 (d, J ¼ 8.2 Hz, 3H), 7.70 (s, 1H), 8.60 (s, 1H), 10.18 (s, 1H).
13C NMR (75 MHz, DMSO-d6), d (ppm): 15.1, 55.5, 63.6, 102.4, 106.5, 111.0,
111.2, 114.3, 122.4, 127.7, 131.0, 131.9, 134.8, 141.5, 148.2, 151.8, 157.2, 159.1,
161.6. Anal. calcd. for C21H19N3O3: C, 69.79; H, 5.30; N, 11.63. Found: C, 69.60;
H, 5.12; N, 11.87.
5-(2-Hydroxyl-4-methoxy-6-methylphenyl)-6-phenylimidazo[1,2-a]pyri-
midine (3g). White solid, mp 231.8–232.9 ꢀC. IR (KBr), n (cmꢁ1): 3407, 2964, 1614,
1585, 1491, 1445, 1332, 1271, 1143, 1038, 836, 704. 1H NMR (300 MHz, DMSO-d6),
d (ppm): 1.67 (s, 3H), 3.73 (s, 3H), 6.33 (s, 1H), 6.42 (s, 1H), 7.16 (s, 1H), 7.33 (s, 5H),
7.72 (s, 1H), 8.66 (s, 1H), 10.09 (s, 1H). 13C NMR (75 MHz, DMSO-d6), d (ppm):
18.8, 54.9, 99.0, 106.8, 110.2, 110.4, 122.8, 127.7, 128.3, 128.7, 134.8, 135.1, 137.9,
140.5, 147.8, 151.0, 156.8, 161.4. Anal. calcd. for C20H17N3O2: C, 72.49; H, 5.17;
N, 12.68. Found: C, 72.27; H, 5.02; N, 12.85.
5-(2-Hydroxyl-3-bromo-4-isopropoxyphenyl)-6-phenylimidazo[1,2-a]pyri-
midine (3h). White solid, mp 262.1–262.9 ꢀC. IR (KBr), n (cmꢁ1): 3504, 3433, 2982,
2608, 1593, 1485, 1263, 1203, 1141, 1109, 1029, 703. H NMR (300 MHz, DMSO-
1
d6), d (ppm): 1.30 (d, J ¼ 5.6 Hz, 6H), 4.58 (m, 1H), 6.68 (s, 1H), 7.24–7.31 (m,
7H), 7.70 (s, 1H), 8.59 (s, 1H), 10.45 (s, 1H). 13C NMR (75 MHz, DMSO-d6), d
(ppm): 22.1, 22.2, 71.9, 101.6, 103.1, 111.4, 112.1, 122.9, 128.1, 128.8, 129.8, 134.3,
135.1, 135.4, 140.4, 148.2, 151.5, 156.4, 156.9. Anal. calcd. for C21H18BrN3O2: C,
59.45; H, 4.28; N, 9.90. Found: C, 59.26; H, 4.41; N, 9.78.
5-(2-Hydroxyl-4-benzyloxyphenyl)-6-(4-methoxyphenyl)imidazo[1,2-a]-
pyrimidine (3i). Yellow solid, mp 157.8–158.9 ꢀC. IR (KBr), n (cmꢁ1): 3417, 3033,
2924, 1610, 1491, 1433, 1249, 1179, 1027, 834, 734; 1H NMR (300 MHz, DMSO-d6),
d (ppm): 3.74 (s, 3H), 5.07 (s, 2H), 6.52 (d, J ¼ 8.4 Hz, 1H), 6.65 (s, 1H), 6.89 (d,
J ¼ 8.4 Hz, 2H), 6.97 (d, J ¼ 8.4 Hz, 1H), 7.21 (d, J ¼ 8.7 Hz, 3H), 7.35–7.47 (m,

5,6-DIPHENYLIMIDAZO[1,2-a]PYRIMIDINE
3597
5H), 7.70 (s, 1H), 8.60 (s, 1H), 10.26 (s, 1H). 13C NMR (75 MHz, DMSO-d6), d
(ppm): 55.5, 69.8, 102.9, 106.8, 111.2, 111.5, 114.3, 122.4, 127.7, 128.1, 128.4,
128.9, 131.0, 132.0, 134.9, 137.1, 141.4, 148.2, 151.8, 157.2, 159.1, 161.4. Anal. calcd.
for C26H21N3O3: C, 73.74; H, 5.00; N, 9.92. Found: C, 73.50; H, 4.89; N, 10.12.
5-(2-Hydroxyl-4-methoxyphenyl)-6-(4-hydroxylphenyl)imidazo[1,2-a]pyri-
midine (3j). White solid, mp 272.3–273.8 ꢀC. IR (KBr), n (cmꢁ1): 3548, 2929, 2600,
1607, 1498, 1442, 1378, 1276, 1219, 1160, 1113, 1027, 956, 832, 716; 1H NMR
(300 MHz, DMSO-d6), d (ppm): 3.74 (s, 3H), 6.42 (t, 1H), 6.55 (s, 1H), 6.69 (d,
J ¼ 7.8 Hz, 2H), 6.92 (t, 1H), 7.06 (d, J ¼ 8.0 Hz, 2H), 7.21 (d, J ¼ 0.9 Hz, 1H),
7.67 (d, J ¼ 1.0 Hz, 1H), 8.57 (s, 1H), 9.54 (s, 1H), 10.17 (s, 1H). 13C HMR
(75 MHz, DMSO-d6), d (ppm): 55.1, 101.6, 105.6, 110.7, 110.9, 115.3, 122.4, 125.5,
130.5, 131.4, 134.0, 141.0, 147.7, 151.5, 156.8, 156.9, 161.8. Anal. calcd. for
C19H15N3O3: C, 68.46; H, 4.54; N, 12.61. Found: C, 68.29; H, 4.75; N, 12.46.
5-(2-Hydroxyl-4-methoxyphenyl)-6-(3,5-diisopropyl-4-hydroxyphenyl)
imidazo[1,2-a]pyrimidine (3k). White solid, mp 247.2–248.6 ꢀC. IR (KBr),
n (cmꢁ1): 3437, 2961, 1619, 1496, 1467, 1318, 1205, 1107, 1033, 880, 723; 1H
NMR (300 MHz, DMSO-d6), d (ppm): 0.99–1.07 (m, 12H), 3.18–3.27 (m, 2H),
3.72 (s, 3H), 6.42 (d, J ¼ 8.3 Hz, 1H), 6.61 (s, 1H), 6.88 (d, J ¼ 8.5 Hz, 1H), 6.92
(s, 2H), 7.23 (s, 1H), 7.67 (s, 1H), 8.19 (s, 1H), 8.69 (s, 1H), 10.24 (s, 1H). 13C
HMR (75 MHz, DMSO-d6), d (ppm): 23.2, 23.3, 26.4, 55.6, 102.1, 106.1, 111.1,
111.8, 123.1, 124.7, 126.4, 131.6, 134.7, 135.5, 141.2, 148.1, 150.6, 151.7, 157.5,
162.3. Anal. calcd. for C25H27N3O3: C, 71.92; H, 6.52; N, 10.06. Found: C, 71.78;
H, 6.35; N, 10.27.
5-(2,4-Dihydroxylphenyl)-6-(4-methoxyphenyl)imidazo[1,2-a]pyrimidine
(3l). White solid, mp 211.2–212.0 ꢀC. IR (KBr), n (cmꢁ1): 3420, 2915, 1607, 1501,
1
1395, 1248, 1177, 1097, 1026, 980, 829, 713; H NMR (300 MHz, DMSO-d6), d
(ppm): 3.74 (s, 3H), 6.23 (d, J ¼ 8.2 Hz, 1H), 6.46 (s, 1H), 6.80 (d, J ¼ 8.3 Hz, 1H),
6.89 (d, J ¼ 8.4 Hz, 2H), 7.19 (d, J ¼ 8.3 Hz, 2H), 7.24 (s, 1H), 7.69 (s, 1H), 8.59
(s, 1H), 9.79 (s, 1H), 9.98 (s, 1H). 13C HMR (75 MHz, DMSO-d6), d (ppm): 55.1,
102.9, 107.4, 109.1, 110.8, 114.0, 121.8, 127.4, 130.7, 131.2, 134.3, 141.5, 147.7,
151.2, 156.7, 158.6, 160.2. Anal. calcd. for C19H15N3O3: C, 68.46; H, 4.54; N,
12.61. Found: C, 68.58; H, 4.37; N, 12.49.
5-(2,4-Dihydroxylphenyl)-6-phenylimidazo[1,2-a]pyrimidine (3m). Yellow
solid, mp 189.1–190.3 ꢀC. IR (KBr), n (cmꢁ1): 3666, 3389, 1611, 1487, 1111, 701,
463. 1H NMR (300 MHz, DMSO-d6), d (ppm): 6.24 (d, 1H), 6.45 (d, 1H),
6.74–6.83 (m, 1H), 7.03–7.30 (s, 6H), 7.73 (t, 1H), 8.57-8.67 (m, 1H), 9.81 (d, 1H),
10.02 (d, 1H). 13C NMR (75 MHz, DMSO-d6), d (ppm): 103.3, 107.9, 109.4, 111.3,
122.6, 127.8, 128.7, 129.8, 131.8, 134.9, 135.8, 142.4, 148.2, 151.5, 157.2, 160.8. Anal.
calcd. for C18H13N3O2: C, 71.28; H, 4.32; N, 13.85. Found: C, 71.09; H, 4.56; N,
14.02.
5-(2,4-Dihydroxylphenyl)-6-(4-hydroxylphenyl)imidazo[1,2-a]pyrimidine
(3n). Yellow solid, mp 212.6–213.9 ꢀC. IR (KBr), n (cmꢁ1): 3558, 3236, 3150, 2929,
1611, 1493, 1243, 837, 555; 1H NMR (300 MHz, DMSO-d6), d (ppm): 6.22 (d,
J ¼ 6.9 Hz, 1H), 6.46 (s, 1H), 6.69 (d, J ¼ 7.7 Hz, 2H), 6.76 (d, J ¼ 8.0 Hz, 1H),

3598
W.-Y. HAN ET AL.
7.05 (d, J ¼ 7.5 Hz, 2H), 7.22 (s, 1H), 7.67 (s, 1H), 8.56 (s, 1H), 9.56 (s, 1H), 9.81 (s,
1H), 9.99 (s, 1H). 13C NMR (75 MHz, DMSO-d6), d (ppm): 103.3, 107.8, 109.7,
111.2, 115.7, 122.6, 126.2, 131.0, 131.8, 134.6, 141.8, 148.1, 151.8, 157.2, 157.3,
160.7. Anal. calcd. for C18H13N3O3: C, 67.71; H, 4.10; N, 13.16. Found: C, 67.52;
H, 4.35; N, 13.29.
5-(2,4-Dihydroxylphenyl)-6-(3-nitro-4-hydroxylphenyl)imidazo[1,2-a]-
pyrimidine (3o). Yellow solid, mp 230.2–231.5 ꢀC. IR (KBr), n (cmꢁ1): 3499, 3454,
1
1613, 1489, 1328, 1267, 1210, 1176, 719; H NMR (300 MHz, DMSO-d6), d (ppm):
6.22 (s, 1H), 6.25 (s, 1H), 6.47 (s, 1H), 6.54 (d, J ¼ 8.0 Hz, 1H), 6.59 (s, 1H), 6.78 (d,
J ¼ 8.3 Hz, 1H), 7.20 (s, 1H), 7.66 (s, 1H), 8.50 (s, 1H), 9.19 (s, 1H), 9.79 (s, 1H), 9.96
(s, 1H). 13C NMR (75 MHz, DMSO-d6), d (ppm): 103.3, 107.7, 109.9, 111.2, 114.6,
115.9, 118.4, 123.4, 126.8, 131.8, 134.4, 136.9, 141.7, 144.0, 148.1, 152.0, 157.1, 160.5.
Anal. calcd. for C18H12N4O5: C, 59.34; H, 3.32; N, 15.38. Found: C, 59.19; H, 3.46;
N, 15.51.
5-(2,4-Dihydroxylphenyl)-6-(3,5-diisopropyl-4-hydroxyphenyl)imidazo[1,2-
a]pyrimidine (3p). Yellow solid, mp 194.7–195.5 ꢀC. IR (KBr), n (cmꢁ1): 3602,
3544, 2964, 1613, 1466, 1442, 1109, 471; 1H NMR (300 MHz, DMSO-d6), d
(ppm): 1.00–1.08 (m, 12H), 3.24 (d, 2H), 6.23 (d, J ¼ 7.8 Hz, 1H), 6.50 (s, 1H),
6.73 (d, J ¼ 8.0 Hz, 1H), 6.95 (t, 2H), 7.24 (d, J ¼ 7.7 Hz, 1H), 7.68 (d, J ¼ 7.9 Hz,
1H), 8.16 (s, 1H), 8.70 (t, 1H), 9.73 (s, 1H), 10.00 (s, 1H). 13C NMR (75 MHz,
DMSO-d6), d (ppm): 23.3, 26.4, 103.1, 107.8, 110.0, 111.1, 123.0, 124.7, 126.5,
131.4, 134.6, 135.4, 141.6, 148.1, 150.6, 151.7, 157.3, 160.7. Anal. calcd. for
C24H25N3O3: C, 71.44; H, 6.25; N, 10.41. Found: C, 71.28; H, 6.41; N, 10.59.
5-(2,4,6-Trihydroxylphenyl)-6-(4-hydroxylphenyl)imidazo[1,2-a]pyrim-
idine (3q). White solid, mp 292.2–293.5 ꢀC. IR (KBr), n (cmꢁ1): 3494, 3445, 3221,
1
1643, 1512, 1438, 1267, 1184, 836; H NMR (300 MHz, DMSO-d6), d (ppm): 5.87
(s, 1H), 6.15 (s, 1H), 6.81 (s, 2H), 7.21–7.30 (m, 2H), 7.48 (d, 2H), 8.04 (d, 1H),
9.51 (s, 1H), 10.47 (s, 1H), 12.96 (s, 1H), 14.76 (s, 1H). 13C NMR (75 MHz,
DMSO-d6), d (ppm): 91.9, 98.8, 107.3, 115.4, 119.9, 124.5, 130.4, 140.0, 141.3,
143.3, 157.2, 163.3, 164.0, 180.1. Anal. calcd. for C18H13N3O4: C, 64.47; H, 3.91;
N, 12.53. Found: C, 64.62; H, 3.69; N, 12.70.
ACKNOWLEDGMENTS
This research was supported by the National Natural Science Foundation of
China (No. 20772076) and the Science and Technology Key Project of Xi’an of
Shaanxi Province (No. CXY08019).
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