Microwave promoted palladium-catalyzed Suzuki-Miyaura cross-coupling reactions of 6-chloropurines with sodium tetraarylborate in water

Article abstract of DOI:10.1016/j.tet.2011.09.082

An efficient method for the synthesis of 6-arylpurines (nucleosides) was developed via Suzuki-Miyaura cross-coupling reactions of 6-chloropurines (nucleosides) and sodium tetraarylborate in neat water (ethanol). The process gave good to high isolated yiel

Full text of DOI:10.1016/j.tet.2011.09.082

Tetrahedron 67 (2011) 9099e9103
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Microwave promoted palladium-catalyzed SuzukieMiyaura cross-coupling
reactions of 6-chloropurines with sodium tetraarylborate in water
,
a
b
a
a
a
Gui-Rong Qu a , Peng-Yang Xin , Hong-Ying Niu , Xin Jin , Xiao-Ting Guo , Xi-Ning Yang ,
*
Hai-Ming Guo a
,
*
a College of Chemistry and Environmental Science, Key Laboratory of Green Chemical Media and Reactions of Ministry of Education, Henan Normal University,
Xinxiang 453007, Henan, China
b School of Chemistry and Chemical Engineering, Henan Institute of Science and Technology, Xinxiang 453003, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 1 August 2011
Received in revised form 16 September 2011
Accepted 20 September 2011
Available online 25 September 2011
An efficient method for the synthesis of 6-arylpurines (nucleosides) was developed via SuzukieMiyaura
cross-coupling reactions of 6-chloropurines (nucleosides) and sodium tetraarylborate in neat water
(ethanol). The process gave good to high isolated yields within a short reaction time under microwave
irradiated conditions.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Palladium-catalyzed
SuzukieMiyaura coupling
6-Chloropurines
Sodium tetraarylborate
Water
Microwave-assisted synthesis
1. Introduction
Based on the review of related literatures, we found that there
are few reports on using sodium tetraarylborate as an arylation
Purine bases and nucleosides have broad application in bi-
ological and pharmaceutical chemistry.1 Especially, purine de-
rivatives with various substituents (such as C-, N-, O-, S-
substituents) at C6 have attracted much more attention in het-
erocyclic compounds because of their unique bioactivities.2 Re-
cently, many reports show that the 6-arylpurine derivatives possess
anti-HCV, cytostatic, and antimycobacterial activities.3 Up to now,
several methodologies were described for the preparation of 6-
arylpurine analogues and nucleosides, such as CeOH bond activa-
tion,4 Kumada coupling reaction,5 Negishi coupling reaction,6 Stille
coupling reaction,7 and SuzukieMiyaura cross-coupling reaction as
another methodology was also developed by several groups, es-
pecially by Hocek’s group8 and Lakshman’s group.9 For example,
Hocek and co-workers reported the synthesis of 6-aryl and heter-
oarylpurine analogues in good yields via cross-coupling reactions
of 6-chloropurines with diverse aryltrifluoroborates using H2O and
MeCN as cosolvent.10
agent for the synthesis of 6-arylpurine derivatives except that Vil-
lemin et al. reported the synthesis of 9-benzyl-6-phenylpuruine in
monomethylformamide.11 Compared with arylboronic acid and
aryltrifluoroborates, sodium tetraarylborate have better atom
economy and good solubility in water, which allow the reaction to
be conducted in neat water under mild reaction conditions.
Over the past few decades, water have been reported to be
a perfect solvent because of its safe, environmentally benign and
cheap properties.12 To the best of our knowledge, no successful
SuzukieMiyaura cross-coupling reaction of 6-chloropurines (nu-
cleosides) with arylation reagents in neat water has been described.
The use of both water as solvent and sodium tetraarylborate as
arylation reagent makes the reaction process more attractive. Based
on our preliminary work on the synthesis of various nucleoside
analogues,13 herein, a green and efficient protocol for the synthesis
of 6-arylpurine nucleosides was described via the SuzukieMiyaura
cross-coupling reactions of 6-chloropurine nucleosides and sodium
tetraarylborate in neat water.
Initially, we tried to optimize the catalytic system and reaction
conditions on the model reaction of 9-benzyl-6-chloro-9H-purine
with sodium tetraphenylborate. Several classic palladium catalysts
for the SuzukieMiyaura reaction were used in this experiment. As
* Corresponding authors. Tel.: þ86 373 3329255; fax: þ86 373 3329276; e-mail
addresses: quguir@sina.com (G.-R. Qu), guohm518@hotmail.com (H.-M. Guo).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.09.082

9100
G.-R. Qu et al. / Tetrahedron 67 (2011) 9099e9103
Table 2
shown in Table 1, Pd(PPh3)4 did not give any product (entry 1), and
PdCl2 gave a trace yield of 3a (entry 2). When we used Pd(OAc)2 or
Pd(dppf)Cl2 as catalyst, a small amount of 3a was obtained (entries
3 and 4). On the other hand, the reaction in the presence of
Pd(PPh3)2Cl2 gave 3a in moderate yield (entry 5), so we chose
Pd(PPh3)2Cl2 as the suitable catalyst. Next, we investigated the ef-
fect of bases. Unfortunately, K2CO3, Cs2CO3, and K2HPO4 did not
give acceptable amount of 3a (entries 6e8), and Na2CO3 only gave
47% yield (entry 5). Because the yield was not satisfied, we decided
to prolong the reaction time. When the reaction time was 20 min,
the yield was low (entry 9, 61%). By increasing the reaction time to
30 min, the yield reached 85% (entry 10). When the reaction time
was 40 min, no significant change in the yield was observed (entry
11, 87%). Reducing the amount of 2a also led to lower yield (entry
12, 65%). Therefore, Pd (PPh3)2Cl2 as the catalyst, Na2CO3 as base
and the reaction time 30 min were the optimized reaction
conditions.
The reaction of Ph4BNa with various 6-chloropurinesa
Entry
Product
R
Yieldb (%)
1
2
3a
3b
85
73
Table 1
3
3c
88
Optimization of reaction conditionsa
4
5
6
3d
3e
3f
98
93
90
Entry
Catalyst
Base
Time (min)
Yieldb (%)
7c
3g
3h
61
92
1
2
3
4
5
6
7
8
Pd(PPh3)4
PdCl2
Pd(OAc)2
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
K2CO3
Cs2CO3
K2HPO4
Na2CO3
Na2CO3
Na2CO3
Na2CO3
10
10
10
10
10
10
10
10
20
30
40
30
0
Trace
10
23
47
Trace
0
Pd(dppf)Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
8
0
a
9
61
85
87
65
Reaction conditions: 1 (0.25 mmol), 2a (0.0938 mmol), Pd(PPh3)2Cl2 5 mol %
based on 1, Na2CO3 (0.5 mmol), solvent: H2O (2 mL), MWI 400 W 100 ꢀC for 30 min.
10
11
12c
b
Isolated yields based on 1.
c
Solvent: EtOH (2 mL), MWI 400 W 90 ꢀC for 30 min.
a
Reaction conditions: 9-benzyl-6-chloro-9H-purine (0.25 mmol), sodium tetra-
phenylborate (0.0938 mmol), catalyst 5 mol % based on 9-benzyl-6-chloro-9H-pu-
rine, base (0.5 mmol), MWI 400 W 100 ꢀC.
(entries 1e6). When we used protected 6-chloropurine nucleoside
as the substrate, the reactions proceeded to give the desired
product in a moderate yields in ethanol (entries 7e10). This might
be due to the relatively poor solubility of sodium carbonate in
ethanol.
b
Isolated yields based on 9-benzyl-6-chloro-9H-purine.
Sodium tetraphenylborate (0.08 mmol) was used.
c
2. Results and discussion
3. Conclusion
To evaluate the generality of the reaction, a number of 6-
chloropurine derivatives with various substituents, including
a sugar carbon substituent at N9, were subjected to the optimized
reaction conditions, affording the desired 6-phenylpurine de-
rivatives in good to excellent isolated yields (61e98%) (Table 2). The
type of substituent at N9 had a little impact on the yield of the
products: the alkyl-substituted substrates gave higher yields, while
the sugar-substituted substrates gave lower yields. When acety-
lated nucleosides (1g) was subjected to the reaction in water, the
CeN glycosidic bond breaking product was obtained. So we used
ethanol as solvent, and then 6-arylpurine nucleoside (3g) was ob-
tained in an acceptable yield (entry 7). Unfortunately, unprotected
6-chloropurine nucleoside gave the CeN glycosidic bond breaking
product both in water and in ethanol.
Intrigued by the results described above, a series of sodium
tetraarylborate were chosen as aryl agents to probe whether the
SuzukieMiyaura reactions could be easily accessed. The results are
shown in Table 3. As expected, when we used 9-benzyl-6-chloro-
9H-purine as the starting material, the reactions proceeded
smoothly to give the corresponding products in good to high yields
We have developed a general, rapid, and eco-friendly protocol
for the synthesis of 6-arylpurines between 6-chloropurine ana-
logues and sodium tetraarylborate under microwave irradiation in
neat water, which avoids the use of toxic solvents, such as aceto-
nitrile, toluene, tetrahydrofuran, 1,4-dioxane or tetrahydropyran.
Furthermore, most of the reactions involved are efficient, giving the
desired compounds in higher yields within short reaction time.
This environmentally friendly procedure represents a promising
green route for the synthesis of these important 6-arylpurine
(nucleoside) compounds.
4. Experimental section
4.1. General information
Melting points were recorded with a micro melting point ap-
paratus and uncorrected. NMR spectra were recorded with a 400
NMR spectrometer for 1H NMR, 100 MHz for 13C NMR. Proton

G.-R. Qu et al. / Tetrahedron 67 (2011) 9099e9103
9101
Table 3
glass vials. The temperature was measured with an IR sensor on
the outer surface of the reaction vials.
The reaction of 6-chloropurines with various sodium tetraarylboratea
4.2. General procedure for the synthesis of NaBAr4
Slow addition of a solution of (60 mmol) of aryl bromides in THF
(20 mL) to Mg turnings (0.60 mol) in THF (5 mL), followed by
refluxing for 1 h, gave a dark gray solution of the aryl Grignard
reagent. After the vial was cooled to room temperature, and then
B(OCH3)3 (0.125 mol) was slowly added to the mixture. The reaction
mixture was stirred until the vial was cooled to room temperature.
Then the reaction mixture was added to Na2CO3 (6.25 g) in water
(50 mL), stirred for 30 min. The resulted mixture was extracted
with ethyl acetate (4ꢁ50 mL) and the combined organic layer was
dried over Na2SO4 and concentrated in vacuo. The residue was
recrystallized from petroleum ether.
Entry
1
Ar
Product
5a
Yieldb (%)
96
2
3
5b
5c
97
92
4.3. General procedure for the SuzukieMiyaura cross-
coupling reaction
9-Benzyl-6-chloro-9H-purine (0.25 mmol) and sodium tetra-
phenylborate (0.0938 mmol) were put in a 10 mL glass vial, and
then Na2CO3 (0.5 mmol), Pd(PPh3)2Cl2 (0.0125 mmol), and water
(2 mL) was added. Then the resulted turbid solution was put into
the cavity of the microwave synthesis apparatus and irradiated at
400 W at 100 ꢀC for 30 min under nitrogen atmosphere. After
completion of the reaction, the vial was cooled to room tempera-
ture. The reaction mixture was extracted with ethyl acetate
(3ꢁ5 mL). The organic layers were collected, combined, dried over
anhydrous Na2SO4, and concentrated under vacuum. The resulted
residue was purified by column chromatography over silica gel
(petroleum ether/ethyl acetate) to give the desired products 3a.
4
5
5d
5e
83
78
6
5f
94
72
7c
5g
4.3.1. 9-Benzyl-6-phenyl-9H-purine(3a). White solid, mp 110e112 ꢀC;
1H NMR (400 MHz, CDCl3)
d
9.06 (s, 1H), 8.79 (q, J¼3.2 Hz, 2H), 8.08 (s,
1H), 7.58e7.52 (m, 3H), 7.36e7.30 (m, 5H), 5.45 (s, 2H). 13C NMR
8c
9c
5h
5i
70
63
(100 MHz, CDCl3) d 154.9, 152.5, 144.2, 135.6, 135.2, 131.0, 130.9, 129.8,
129.1, 128.7, 128.6, 127.8, 47.2. HRMS: calcd for C18H15N4 [MþH]þ
287.1291, found 287.1296.
4.3.2. 9-(2-Chlorobenzyl)-6-phenyl-9H-purine (3b). White solid,
mp 142e144 ꢀC; 1H NMR (400 MHz, CDCl3)
d
9.05 (s, 1H), 8.79e8.77
(m, 2H), 8.20 (s, 1H), 7.59e7.52 (m, 3H), 7.43 (t, J¼7.6 Hz, 1H),
7.31e7.24 (m, 3H), 5.59 (s, 1H). 13C NMR (100 MHz, CDCl3)
155.0,
10c
5j
54
d
152.6, 152.5, 144.3, 135.6, 133.5, 132.7, 131.0, 130.8, 130.3, 130.1,
130.0, 129.8, 128.7, 127.5, 44.9. HRMS: calcd for C18H14ClN4 [MþH]þ
321.0902, found 321.0906.
a
Reaction conditions: 4 (0.25 mmol), 2 (0.0938 mmol), Pd(PPh3)2Cl2 5 mol %
based on 4, Na2CO3 (0.5 mmol), solvent: H2O (2 mL), MWI 400 W 100 ꢀC for 30 min.
b
Isolated yields based on 4.
Solvent: EtOH (2 mL), MWI 400 W 90 ꢀC for 30 min.
c
4.3.3. 6,9-Diphenyl-9H-purine (3c). White solid, mp 122e123 ꢀC;
1H NMR (400 MHz, CDCl3)
d
9.10 (s, 1H), 8.82 (q, J¼3.3 Hz, 2H), 8.41
(s, 1H), 7.76 (q, J¼3.2 Hz, 2H), 7.65e7.53 (m, 5H), 7.51 (t, J¼7.6 Hz,
1H). 13C NMR (100 MHz, CDCl3)
156.2, 155.5, 153.1, 143.3, 135.5,
chemical shifts
d were given in parts per million relative to tet-
ramethylsilane (0.00 ppm) in CDCl3 or to the residual proton
signals of the deuterated solvent CD3OD (3.31 ppm). High reso-
lution mass spectra were taken with a 3000 mass spectrometer,
using Waters Q-TofMS/MS system. For column chromatography
200e300 mesh silica gel (GF254) was used as the stationary phase.
All reactions were monitored by thin layer chromatography (TLC).
All reagents and solvents were purchased from commercial
sources and purified commonly before used. All microwave irra-
diation experiments were carried out in the cavity of a commer-
cially available single-mode microwave synthesis apparatus
equipped with a high sensitivity infrared sensor for temperature
control and measurement (MAS-I, Sineo Microwave Chemical
Technology Co. Ltd., Shanghai, PR China) with continuous irradi-
ation power from 0 to 600 W. The reactions were carried out in
d
131.5, 131.1, 130.0, 129.8, 128.7, 128.6, 123.8. HRMS: calcd for
C17H13N4 [MþH]þ 273.1135, found 273.1142.
4.3.4. 9-Methyl-6-phenyl-9H-purine
(3d). White
8.89 (s,1H), 8.67 (d, J¼7.2 Hz,
solid,
mp
112e114 ꢀC; 1H NMR (400 MHz, CDCl3)
d
2H), 7.87 (s, 1H), 7.47e7.41 (m, 3H), 3.68 (s, 3H). 13C NMR (100 MHz,
CDCl3)
d 154.2, 152.6, 152.2, 144.7, 135.6, 130.8, 129.6, 128.5, 29.6.
HRMS: calcd for C12H11N4 [MþH]þ 211.0978, found 211.0986.
4.3.5. 9-Ethyl-6-phenyl-9H-purine (3e). White solid, mp 67e68 ꢀC;
1H NMR (400 MHz, CDCl3)
d
8.93 (s, 1H), 8.72 (d, J¼7.6 Hz, 2H), 7.99
(s, 1H), 7.49e7.42 (m, 3H), 4.19 (q, J¼7.2 Hz, 2H), 1.44 (t, J¼7.6 Hz,
3H). 13C NMR (100 MHz, CDCl3)
154.5, 152.2, 152.1, 143.8, 135.7,
d

9102
G.-R. Qu et al. / Tetrahedron 67 (2011) 9099e9103
131.1, 130.8, 129.7, 128.5, 38.8, 15.2. HRMS: calcd for C13H13N4
47.5. HRMS: calcd for
423.1041.
C
20H13F6N4 [MþH]þ 423.1039, found
[MþH]þ 225.1135, found 225.1142.
4.3.6. 6-Phenyl-9-propyl-9H-purine (3f). Light yellow powder, mp
4.3.14. 9-Benzyl-6-(4-ethylphenyl)-9H-purine (5f). White solid, mp
105e106 ꢀC; 1H NMR (400 MHz, CDCl3)
9.02 (s, 1H), 8.72 (d,
78e80 ꢀC; 1H NMR (400 MHz, CDCl3)
d
8.96 (s, 1H), 8.73 (d,
d
J¼7.2 Hz, 2H), 8.02 (s, 1H), 7.52e7.45 (m, 3H), 4.16 (t, J¼7.2 Hz, 2H),
J¼8 Hz, 2H), 8.05 (s, 1H), 7.38 (d, J¼8.4 Hz, 2H), 7.33e7.27 (m, 5H),
1.88 (q, J¼7.3 Hz, 2H), 0.90 (t, J¼7.2 Hz, 3H). 13C NMR (100 MHz,
5.41 (s, 2H), 2.72 (q, J¼7.6 Hz, 2H), 1.27 (t, J¼7.6 Hz, 3H). 13C NMR
CDCl3)
d
154.6, 152.4, 152.2, 144.3, 135.7, 131.0, 130.9, 129.7, 128.6,
(100 MHz, CDCl3) d 154.9, 152.6, 152.4, 147.7, 143.9, 135.3, 133.1,
45.5, 23.2, 11.2. HRMS: calcd for C14H15N4 [MþH]þ 239.1291, found
130.7, 129.8, 129.1, 128.5, 128.3, 127.8, 47.2, 29.0, 15.5. HRMS: calcd
239.1295.
for C20H19N4 [MþH]þ 315.1604, found 315.1608.
4.3.7. 2-(Acetoxymethyl)-5-(6-phenyl-9H-purin-9-yl)tetrahydrofu-
4.3.15. 2-(Acetoxymethyl)-5-(6-p-tolyl-9H-purin-9-yl)tetrahydrofu-
ran-3,4-diyl diacetate (3g). Light yellow oil; 1H NMR (400 MHz,
ran-3,4-diyl diacetate (5g). Colorless oil; 1H NMR (400 MHz,
CDCl3)
d
9.02 (s, 1H), 8.73 (q, J¼3 Hz, 2H), 8.28 (s, 1H), 7.58e7.52 (m,
CDCl3)
d
9.02 (s, 1H), 8.73 (q, J¼3 Hz, 2H), 8.28 (s, 1H), 7.58e7.52
3H), 6.29 (d, J¼5.2 Hz, 1H), 6.01 (t, J¼5.2 Hz, 1H), 5.70 (t, J¼4.8 Hz,
1H), 4.48e4.45 (m, 2H), 4.39 (q, J¼6 Hz, 1H), 2.14 (d, J¼10.4 Hz, 6H),
(m, 3H), 6.29 (d, J¼5.2 Hz, 1H), 6.01 (t, J¼5.2 Hz, 1H), 5.70 (t,
J¼4.8 Hz, 1H), 4.48e4.45 (m, 2H), 4.39 (q, J¼6 Hz, 1H), 2.14 (d,
J¼10.4 Hz, 6H), 2.07 (d, J¼6 Hz, 3H). 13C NMR (100 MHz, CDCl3)
2.07 (d, J¼6 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d 170.3, 169.6, 169.4,
155.5, 152.7, 152.0, 142.6, 135.3, 131.6, 131.2, 129.8, 128.7, 86.4, 80.3,
73.1, 70.6, 63.1, 20.8, 20.6, 20.4. HRMS: calcd for C22H23N4O7
[MþH]þ 455.1561, found 455.1564.
d 170.4, 169.6, 169.4, 155.5, 152.6, 142.9, 142.3, 135.7, 132.6, 131.4,
129.8, 129.5, 128.7, 86.3, 80.3, 73.1, 70.7, 63.1, 21.9, 20.8, 20.6, 20.4.
HRMS: calcd for C23H24N4NaO7 [MþNa]þ 491.1537, found
491.1545.
4.3.8. 9-Butyl-6-phenyl-9H-purin-2-amine (3h). White solid, mp
108e110 ꢀC; 1H NMR (400 MHz, CDCl3)
d
8.62 (q, J¼3.2 Hz, 2H), 7.80
4.3.16. 2-(Acetoxymethyl)-5-(6-m-tolyl-9H-purin-9-yl)tetrahydrofu-
(s, 1H), 7.54e7.49 (m, 3H), 5.21 (s, 2H), 4.11 (t, J¼7.2 Hz, 2H),
ran-3,4-diyl diacetate (5h). Light yellow oil; 1H NMR (400 MHz,
1.89e1.81 (m, 2H),1.43e1.33 (m, 2H), 0.97 (t, J¼7.6 Hz, 3H). 13C NMR
CDCl3)
d
8.98 (s, 1H), 8.54 (d, J¼7.6 Hz, 2H), 8.48 (s, 1H), 8.26 (s, 1H),
(100 MHz, CDCl3)
d
159.3, 155.5, 154.4, 142.0, 135.6, 132.6, 130.7,
7.41 (t, J¼7.6 Hz, 1H), 7.30 (d, J¼7.6 Hz, 1H), 6.26 (d, J¼5.2 Hz, 1H),
5.99 (t, J¼5.6 Hz, 1H), 5.68 (t, J¼5.2 Hz, 1H), 4.45e4.41 (m, 2H), 4.36
(q, J¼6 Hz, 1H), 2.44 (s, 3H), 2.10 (d, J¼10 Hz, 6H), 2.04 (d, J¼5.6 Hz,
129.5, 128.5, 128.0, 125.6, 43.2, 31.8, 19.9, 13.6. HRMS: calcd for
C15H18N5 [MþH]þ 268.1557, found 268.1560.
3H). 13C NMR (100 MHz, CDCl3)
d 170.3, 169.6, 169.4, 155.6, 152.6,
4.3.9. 9-Benzyl-6-p-tolyl-9H-purine
126e128 ꢀC; 1H NMR (400 MHz, CDCl3)
J¼8.4 Hz, 2H), 8.07 (s, 1H), 7.37e7.30 (m, 7H), 5.45 (s, 2H), 2.44
(s, 3H). 13C NMR (100 MHz, CDCl3)
154.9, 152.6, 152.4, 143.9,
(5a). White
solid,
mp
151.9, 142.6, 138.3, 135.2, 132.0, 131.6, 130.0, 128.6, 127.2, 86.3, 80.3,
73.0, 70.6, 63.0, 21.6, 20.8, 20.5, 20.4. HRMS: calcd for
C23H24N4NaO7 [MþNa]þ 491.1537, found 491.1541.
d
9.03 (s, 1H), 8.70 (d,
d
141.4, 135.2, 132.9, 130.7, 129.7, 129.4, 129.1, 128.5, 127.8, 47.2,
21.7. HRMS: calcd for C19H17N4 [MþH]þ 301.1448, found
301.1450.
4.3.17. 2-(Acetoxymethyl)-5-(6-(4-ethylphenyl)-9H-purin-9-yl)-tet-
rahydrofuran-3,4-diyl diacetate (5i). Light yellow oil; 1H NMR
(400 MHz, CDCl3)
d
9.00 (s, 1H), 8.67 (d, J¼8 Hz, 2H), 8.26 (s, 1H),
7.39 (d, J¼8 Hz, 2H), 6.29 (d, J¼5.2 Hz, 1H), 6.01 (t, J¼5.6 Hz, 1H),
5.71 (t, J¼5.2 Hz, 1H), 4.46 (q, J¼4.1 Hz, 2H), 4.39 (q, J¼5.9 Hz,
1H), 2.73 (q, J¼7.6 Hz, 2H), 2.14 (d, J¼10 Hz, 6H), 2.08 (d,
J¼6.8 Hz, 3H), 1.28 (t, J¼7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3)
4.3.10. 9-Benzyl-6-m-tolyl-9H-purine
(5b). White solid, mp
9.05(s,1H), 8.61 (d, J¼7.6 Hz,
136e137 ꢀC; 1H NMR (400 MHz, CDCl3)
d
2H), 8.55 (s,1H), 8.09 (s,1H), 7.45 (t, J¼7.6 Hz,1H), 7.36e7.30 (m, 6H),
5.46 (s, 2H), 2.48 (s, 3H). 13C NMR (100 MHz, CDCl3)
d
155.1, 152.6,
d 170.3, 169.6, 169.4, 155.6, 152.7, 151.9, 147.9, 142.3, 132.8, 131.4,
152.5, 144.1, 138.3, 135.5, 135.2, 131.9, 131.0, 130.0, 129.1, 128.6, 128.5,
127.8, 127.2, 47.2, 21.6. HRMS: calcd for C19H17N4 [MþH]þ 301.1448,
found 301.1451.
129.8, 128.3, 86.3, 80.3, 73.1, 70.6, 63.1, 29.0, 20.8, 20.6, 20.4, 15.4.
HRMS: calcd for C24H26N4NaO7 [MþNa]þ 505.1694, found
505.1697.
4.3.11. 9-Benzyl-6-(3,5-dimethylphenyl)-9H-purine (5c). Light yel-
4.3.18. 2-(Acetoxymethyl)-5-(6-(3,5-bis(trifluoromethyl)phenyl)-9H-
purin-9-yl)tetrahydrofuran-3,4-diyl diacetate (5j). Light yellow oil;
low powder, mp 144e145 ꢀC; 1H NMR (400 MHz, CDCl3)
d
9.05 (s,
1H), 8.41 (s, 2H), 8.08 (s, 1H), 7.37e7.26 (m, 5H), 7.17 (s, 1H), 5.44
(s, 2H), 2.45 (s, 6H). 13C NMR (100 MHz, CDCl3)
155.3, 152.5,
1H NMR (400 MHz, CDCl3)
d 9.35 (s, 2H), 9.05 (s, 1H), 8.36 (s, 1H),
d
8.01 (s, 1H), 6.31 (d, J¼5.2 Hz, 1H), 6.02 (t, J¼5.2 Hz, 1H), 5.71 (t,
144.0, 138.2, 135.5, 135.2, 132.8, 130.9, 129.1, 128.5, 127.85, 127.5,
47.2, 21.5. HRMS: calcd for C20H19N4 [MþH]þ 315.1604, found
315.1613.
J¼4.8 Hz, 1H), 4.51e4.46 (m, 2H), 4.41 (q, J¼5.4 Hz, 1H), 2.16 (d,
J¼9.2 Hz, 6H), 2.10 (s, 3H). 13C NMR (100 MHz, CDCl3)
d 170.5, 169.7,
169.5, 152.6, 152.5, 151.3, 143.7, 137.3, 132.1, 131.8, 129.8, 124.6, 121.9,
86.6, 80.4, 73.1, 70.6, 63.0, 20.8, 20.5, 20.4. HRMS: calcd for
C24H20F6N4NaO7 [MþNa]þ 613.1128, found 613.1136.
4.3.12. 9-Benzyl-6-(4-methoxyphenyl)-9H-purine (5d). White solid,
mp 143e144 ꢀC; 1H NMR (400 MHz, CDCl3)
d
8.99 (s, 1H), 8.81 (q,
J¼3 Hz, 2H), 8.60 (s, 1H), 7.36e7.30 (m, 5H), 7.07 (q, J¼7.3 Hz, 2H),
5.46 (s, 2H), 3.89 (s, 3H). 13C NMR (100 MHz, CDCl3)
162.0, 154.6,
Acknowledgements
d
152.6, 152.3, 143.6, 135.3,131.5,130.4, 129.1,128.5,128.3,127.8,114.1,
55.4, 47.2. HRMS: calcd for C19H17N4O [MþH]þ 317.1397, found
317.1400.
We are grateful for financial support from the National Nature
Science Foundation of China (Grant Nos 20802016, 21072047, and
21072047), the Program for New Century Excellent Talents in
University of Ministry of Education (No. NCET-09-0122), Excellent
Youth Foundation of Henan Scientific Committee (No.
114100510012), the Program for Changjiang Scholars and In-
novative Research Team in University (IRT1061), the National Stu-
dents Innovation Experiment Program, and the Excellent Youth
Program of Henan Normal University.
4.3.13. 9-Benzyl-6-(3,5-bis(trifluoromethyl)phenyl)-9H-purine
(5e). White solid, mp 125e128 ꢀC; 1H NMR (400 MHz, CDCl3)
d
9.43
(s, 2H), 9.10 (s, 1H), 8.17 (s, 1H), 8.01 (s, 1H), 7.39e7.33 (m, 5H), 5.52
(s, 2H). 13C NMR (100 MHz, CDCl3)
153.0, 152.5, 150.9, 145.1, 137.7,
134.8, 132.1, 131.8, 131.2,129.8, 129.2, 128.8, 127.9, 124.7,124.1, 122.0,
d

G.-R. Qu et al. / Tetrahedron 67 (2011) 9099e9103
9103
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hedron 1994, 50, 9743e9756; (d) Prasad, A. S. B.; Stevenson, T. M.; Citineni, J. R.;
Nyzan, V.; Knochel, P. Tetrahedron 1997, 53, 7237e7254.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tet.2011.09.082.
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