An efficient synthesis of mono and bis-1,2,3-triazole AZT derivatives via copper(I)-catalyzed cycloaddition

Article abstract of DOI:10.1002/jccs.201190053

An efficient synthesis of novel mono and bis-1,2,3-triazoles 3'-azido-2'-deoxythymidine (AZT) derivatives via copper(I)-catalyzed 1,3-dipolar cycloaddition reaction is described. Starting from AZT and terminal alkyne derivatives, mono and bis-1,2,3-triazo

Full text of DOI:10.1002/jccs.201190053

24
Journal of the Chinese Chemical Society, 2011, 58, 24-30
Communication
An Efficient Synthesis of Mono and Bis-1,2,3-triazole AZT Derivatives via
Copper(I)-catalyzed Cycloaddition
Jin-Wei Yuan,a Ling-Bo Qu,a,b Xiao-Lan Chen,b,* Zhi-Bo Qu,b Xiang-Qian Liub and Dian-Dian Keb
aSchool of Chemistry & Chemical Engineering, Henan University of Technology,
Zhengzhou 450001, P. R. China
bDepartment of Chemistry, Zhengzhou University, Key Laboratory of Chemistry Biology and Organic
Chemistry, Zhengzhou 450052, P. R. China
Received July 27, 2010; Accepted December 8, 2010; Published Online December 28, 2010
An efficient synthesis of novel mono and bis-1,2,3-triazoles 3¢-azido-2¢-deoxythymidine (AZT) de-
rivatives via copper(I)-catalyzed 1,3-dipolar cycloaddition reaction is described. Starting from AZT and
terminal alkyne derivatives, mono and bis-1,2,3-triazole AZT derivatives are regioselectively obtained in
good yields under mild conditions using CuSO4·5H2O and sodium ascorbate as a catalyst system, and
t-BuOH/H2O (1:1, v/v) as a co-solvent. The structures of these compounds were elucidated by IR, HR MS
and NMR.
Keywords: 3¢-Azido-2¢-deoxythymidine (AZT); 1,2,3-Triazole; 1,3-Dipolar cycloaddition.
INTRODUCTION
covered by the groups of Sharpless and Meldal,11,12 is a
useful approach. This characteristic of the reaction is its
complete specificity, biocompatibility of the reactants and
high degree of dependability. Cu(I)-catalyzed 1,3-dipolar
cycloaddition is premiere example of a click chemistry em-
ployed in a wide range of applications within drug discov-
ery, including modification of cell surfaces, specific label-
ing of virus particles, proteins, oligonucleotides and syn-
thesis of new glycoproteins and dendrimers.13
Nucleoside analogues have long been used to treat
various viral-induced tumors.3¢-Azido-2¢-deoxythymidine
(AZT) (Fig. 1a), as a nucleoside analogue, has been re-
ported to possess high activity against AIDS, owing to its
potential inhibiting property to HIV reverse transcriptase.1
Azoles are the largest class of antifungal agents in clinical
use.2 1,2,3-Triazole can serve as a suitable moieties in these
drugs since it is stable to metabolic degradation and sus-
ceptible to hydrogen bonding beneficial for the affinity
with molecular targets and solubility.3,4 Compounds con-
taining a 1,2,3-triazole moiety show various biological ac-
tivities such as anti-HIV,5 anti-microbial,6 anti-allergic,7
and selective b3 adrenergic receptor agonist.8 Ribavirin
(Fig. 1b) is the first synthetic and so far the only small mol-
ecule triazole nucleoside drug for treating viral infections
caused by hepatitis C virus (HCV).9 A number of synthetic
methodologies have been developed for the preparation of
various nucleoside analogues containing 1,2,3-triazole
moiety since then.10
Generation of the 1,2,3-triazoles moiety in the 3¢-po-
sition of 2¢-deoxyribose nucleosides through the 1,3-di-
polar cycloaddition of organic azides with alkynes has been
NH2
O
O
N
NH
N
HO
HO
N
N
O
O
O
N3
HO
OH
With respect to introducing 1,2,3-triazole groups in
to organic molecules, copper(I)-catalyzed 1,3-dipolar cy-
cloaddition reaction of azides and terminal alkynes, dis-
a. AZT
b. Ribavirin
Fig. 1. The structures of AZT and Ribavirin.
Project was supported by NSFC (No. 20472076 and 21072178) and ISPHN
* Corresponding author. Tel: +86-371-67767051; Fax: +86-371-67767051; E-mail: chenxl@zzu.edu.cn

Mono and Bis-1,2,3-triazole AZT Derivatives
J. Chin. Chem. Soc., Vol. 58, No. 1, 2011 25
reported by Wigerinck P.’s and Tourirte M.’s groups.14,15
However, these cycloaddition reactions were typically car-
ried out in refluxing organic solvents (DME, toluene) con-
ditions in which labile molecules may not survive. The
cycloadditions performed under the relatively harsh reac-
tion conditions, for example, at relatively high tempera-
ture, sometimes resulted in low yields and/or poor regio-
selectivity.16 The main purpose of our work is to provide a
practical method, through 1,3-dipolar cycloaddition of
AZT with alkynes, to regioselectively synthesize a series of
novel 2¢-deoxythymidine derivatives linked with 1,2,3-tri-
azoles attached by various aromatic moieties, including
chrysin groups as shown in Scheme I, and also bis-triazole
AZT derivatives as shown in Scheme II. Interestingly
enough, it was found that, as described in the following of
this paper, even at room temperature, a regioseletive syn-
thesis of novel 1,2,3-triazole derivatives of AZT could suc-
cessfully been carried out by 1,3-dipolar cycloaddition us-
ing CuSO4/sodium ascorbate as the catalyst, t-BuOH-H2O
(1:1 v/v) as the solvent in relatively high yields. It is espe-
cially worth mentioning that the regioselective products of
1,3-dipolar cycloaddition reaction are insoluble in the reac-
tion solvent (t-BuOH-H2O (1:1 v/v)), and thus they precipi-
tates as they are formed. It is therefore easy to purify the
products by simply washing with water. Chrysin, an impor-
tant naturally occurring flavonoid, possessing multiple bio-
logical activities,17 such as antiviral,18 antibacterial,19 anti-
oxidant,20 anticancer activities,21 was also successfully in-
corporate in the related 1,2,3-triazole AZT modification by
using the reaction condition mentioned above. Finally a
series of novel target products were obtained in relatively
high yield under mild reaction conditions as described in
Scheme I Synthesis of 1,2,3-triazole AZT derivatives

26 J. Chin. Chem. Soc., Vol. 58, No. 1, 2011
Yuan et al.
Scheme II Synthesis of bis-1,2,3-triazoles AZT derivatives
the following.
ligand in organic or aqueous solvent for achieving higher
catalytic efficiency.22,24 CuSO4·5H2O and sodium ascor-
bate as a catalyst system, firstly employed by Sharpless and
co-workers for the in situ generation of Cu(I),11 has been
applied to lots of 1,3-dipolar cycloadditions with a rela-
tively high catalytic stability and efficiency.25 Also CuSO4·
5H2O and sodium ascorbate show very appreciable solubil-
ity in the properly chosen cosolvent (t-BuOH-H2O (1:1
v/v)) used in the following 1,3-dipolar cycloaddition. Con-
sidering the appreciable stability and solubility of catalysts
in the related reaction system, CuSO4·5H2O/sodium ascor-
bate was therefore chosen as an appropriate catalyst system
for the 1,3-dipolar cycloaddition.
RESULTS AND DISCUSSION
The 1,3-dipolar cycloaddition reaction of organic
azides and alkynes has recently regained attention, owing
to the discovery that the rate of the cycloaddition can be ac-
celerated greatly by Cu(I) catalysis.11,22 The active Cu(I)
ion can be generated directly from Cu(I) salts or in-situ
from Cu(II) salts in presence of a reducing agent (often so-
dium ascorbate or metallic copper). Direct use of Cu(I)
salts as catalysts should be avoided in some cases because
of their extremely low solubility in aqueous media and their
tendency to disproportionate quickly to Cu(0) and Cu(II)
under some reaction conditions.23 Also in most occasions
Cu(I) salts must be used in conjunction with a base or
The solubility of reactants involved in 1,3-dipolar
cycloaddition reaction is another major factor affecting the

Mono and Bis-1,2,3-triazole AZT Derivatives
J. Chin. Chem. Soc., Vol. 58, No. 1, 2011 27
reaction efficiency. Different solvents, such as tert-butyl
alcohol, ethanol, water and the related cosolvents seen by
previous reports were employed to carry out the 1,3-dipolar
cycloaddition.11,26 Considering poor solubility of the re-
lated aromatic reactants, especially chrysin, in pure water
and poor solubility of the Cu(II) salts in organic solvents,
t-BuOH/H2O co-solvent at ratio 1:1 (v/v) was chosen as the
reaction solvent to enhance the solubility of either the re-
lated aromatic reactants or the Cu(II) salts. As described in
the following section, the cycloaddition reaction of various
aromatic terminal alkyne and AZT was indeed proceeded
efficiently at room temperature under the designed reaction
condition using CuSO4·5H2O/sodium ascorbate as a cata-
lyst system, and t-BuOH/H2O (1:1, v/v) as a cosolvent.
The title compounds were synthesized as shown in
Scheme I and II. Under reflux condition the reaction form-
ing different aryl propargyl ethers took place using differ-
ent aromatic phenols and propargyl bromine as reactants in
acetone. Using CuSO4·5H2O and sodium ascorbate as a
catalyst system, and t-BuOH/H2O (1:1, v/v) as a solvent,
the reactions between 3¢-azido group of AZT and acetylene
group of aryl propargyl ethers 2 at room temperature led to
a series of mono and bis-1,2,3-triazole AZT derivatives via
1,3-dipolar cycloaddition reaction. The regioselective
products of 1,3-dipolar cycloaddition reaction are insolu-
ble in the reaction solvent (t-BuOH-H2O (1:1 v/v)), and
thus they precipitates as they are formed. The pure products
(3a-d) were obtained in relatively high yields after a simple
filtration and washing with water. The conversion of aryl
propargyl ether into the corresponding mono-1,2,3-triazole
AZT derivatives (3a-d) was almost quantitative and iso-
lated yields of products were high (³ 95%). The conversion
of chrysin-7-yl propargyl ether (2e) into the corresponding
1,2,3-triazole AZT (3e) was relatively low and isolated
yields of products was 72%, and the conversion of bis-
(ethynyloxy) benzene (5a-c) into the corresponding bis-
1,2,3-triazole AZT (6a-c) was comparably higher and
isolated yields of products were more than 92%.
1,4-substituted trazole products formed by 1,3-dipolar
cycloaddition reaction. NOE effects between the triazole
proton and the 4¢-proton of glucoyl were also observed,
suggesting that the triazole proton and N-substituent are in
close proximity as in the 1,4-substituted triazole.
CONCLUSION
An efficient synthesis of novel 1,2,3-triazole and
bis-1,2,3-triazoles 3¢-azido-2¢-deoxythymidine (AZT) de-
rivatives via copper(I)-catalyzed 1,3-dipolar cycloaddition
reaction is established. Mono and bis-1,2,3-triazole AZT
derivatives are regioselectively obtained in good yields un-
der mild conditions using CuSO4·5H2O and sodium ascor-
bate as a catalyst system, and t-BuOH/H2O (1:1, v/v) as a
solvent.
EXPERIMENTAL
Acetone was dried with K2CO3, and then distilled. IR
spectra were recorded on a Shimadazuir-408. 1H, 13C NMR
spectra were recorded on a Bruker Avance 400 MHz spec-
trometer operating at 400.13 and 100.61 MHz, respec-
tively, with 13C spectra being recorded as proton-decoup-
led. NMR spectra were recorded in DMSO or CDCl3 at
room temperature (20 ± 3 °C). 1H and 13C chemical shifts
are quoted in parts per million downfield from TMS. J val-
ues refer to coupling constants, and signal splitting patterns
are described as singlet (s), doublet (d), triplet (t), quartet
(q), multiplet (m), or combinations thereof. TLC was per-
formed on silica gel plates and preparative chromatograph
on columns of silica gel (200-300 mesh). High resolution
mass spectra (HR MS) were obtained on a Waters Micro-
mass Q-Tof MicroTM instrument using the ESI technique.
General procedures
Synthesis of mono-1,2,3-triazole AZT derivatives
(3a-e)
To a solution of aromatic phenols (1a-e) (1.0 mmol)
in dry acetone (10 mL) was added anhydrous potassium
carbonate (0.276 g, 2 mmol), and the mixture was stirred
for 0.5 h, then propargyl bromide (0.118 g, 1.0 mmol) were
added. The resulting mixture was stirred and refluxed for
an additional 20 h. The mixture was cooled and filtered,
and the filtrate was evaporated. The residue was dissolved
in dichloromethane(50 mL) and washed with water (2 × 50
mL) and saturated brine (1 × 50 mL). The organic phase
was dried over anhydrous sodium sulfate. The crude prod-
uct was purified with column chromatograph on silica gel
and eluted with petroleum ether:ethyl acetate (1:1, v/v), to
A high regioselectivity of the copper(I)-catalyzed
1,3-dipolar cycloaddition reaction was observed. Only 1,4-
rather than 1,5-substituted [1,2,3]-trazole was formed based
on NMR data analysis of final products. It was reported that
the triazole proton in 1,4-substituted trazoles was always
shifted considerably downfield (about 8.50 ppm) com-
pared to 1,5-substituted trazoles (about 8.23 ppm).22 The
fact that the triazole proton of products 3a-e and 6a-c were
found at 8.39-8.55 ppm gives a decisive support for the

28 J. Chin. Chem. Soc., Vol. 58, No. 1, 2011
Yuan et al.
give aryl propargyl ethers (2a-e).
Compound 3a
Compound 2a
Yieled: 96.0%; m.p. 212-213 °C; IR (KBr) n (cm-1):
3480 (NH), 1709 (C=O), 3076, 2929 (CH3), 1277 (C-O);
HR MS m/z: 430.1722 [M + H]+, (calculated for
C20H24N5O6 430.1727); 1H NMR (DMSO) d: 11.36 (s, 1H,
-NH), 8.40 (s, 1H, =CH), 7.82 (s, 1H), 6.99 (m, 2H), 6.79
(m, 2H), 6.44 (t, J = 6.8 Hz, 1H), 5.39-5.37 (m, 1H),
5.29-5.27 (m, 1H), 5.08 (s, 1H), 4.24-4.21 (m, 1H), 3.68 (s,
3H, OCH3), 3.73-3.61 (m, 2H), 2.76-2.65 (m, 2H), 1.81 (s,
3H, CH3); 13C NMR (DMSO) d: 164.2 (C=O), 154.1
(C=O), 152.5, 150.9, 143.7, 136.7, 124.5, 116.1, 115.1,
110.1, 84.9, 84.3, 62.1, 61.2, 59.7, 55.8, 37.6, 12.7 (CH3).
Compound 3b
Yellow oily liquid, yield: 96.0%; 1H NMR (CDCl3) d:
6.93 (m, 2H), 6.85 (m, 2H), 4.65 (d, J = 2.4 Hz, 2H, OCH2),
3.78 (s, 3H, OCH3), 2.51 (t, J = 2.4 Hz, 1H, ºCH). 13C
NMR (CDCl3) d: 154.5, 151.6, 116.1, 114.6, 78.9 (CHºC),
75.4 (CHºC), 56.5 (OCH2), 55.6 (OCH3).
Compound 2b
Colorless liquid, yield: 97.0%; 1H NMR (CDCl3) d:
7.29 (m, 2H), 6.91 (m, 2H), 4.66 (d, J = 2.4 Hz, 2H, OCH2),
2.57 (t, J = 2.4 Hz, 1H, ºCH); 13C NMR (CDCl3) d: 156.1
(O-C), 129.4, 126.5, 116.3, 78.3 (CHºC), 76.0 (CHºC),
56.0 (OCH2).
Compound 2c
Yieled: 95.0%; m.p. 212-213 °C; IR (KBr) n (cm-1):
3491 (NH), 1676 (C=O), 3080, 2935 (CH3), 1275 (C-O);
HR MS m/z: 434.1229 [M + H]+, (calculated for
C19H21ClN5O5 434.1231); 1H NMR (DMSO) d: 11.36 (s,
1H, -NH), 8.42 (s, 1H, =CH), 7.81 (s, 1H), 7.35 (d, J = 8.8
Hz, 2H), 7.08 (d, J = 8.4 Hz, 2H), 6.43 (t, J = 6.4 Hz, 1H),
5.39 (m, 1H), 5.31 (m, 1H), 5.15 (s, 1H), 4.21 (m, 1H), 3.71
(m, 2H), 2.74 (m, 2H), 1.80 (s, 3H, CH3); 13C NMR
(DMSO) d: 164.2 (C=O), 157.3 (C=O), 150.9, 143.1,
136.7, 129.7, 125.0, 124.8, 116.9, 110.1, 84.9, 84.3, 61.8,
61.2, 59.8, 37.6, 12.7 (CH3).
White solid, yield: 94.0%; 1H NMR (CDCl3) d: 8.25
(m, 1H), 7.75 (m, 1H), 7.42 (m, 3H), 7.31 (m, 1H), 6.85 (m,
1H), 4.80 (d, J = 2.4 Hz, 2H, OCH2), 2.49 (t, J = 2.4 Hz, 1H,
ºCH); 13C NMR (CDCl3) d: 153.4 (O-C), 134.6, 127.6,
126.6, 125.7, 125.5, 122.1, 121.3, 105.6, 78.7 (CHºC),
75.7 (CHºC), 56.2 (OCH2).
Compound 2d
White solid, yield: 95.0%; 1H NMR (CDCl3) d: 7.72-
7.76 (m, 3H), 7.43 (m, 1H), 7.36 (m, 1H), 7.16-7.21 (m,
2H), 4.78 (s, 2H, OCH2), 2.53 (s, 1H, ºCH); 13C NMR
(CDCl3) d: 155.5 (O-C), 134.3, 129.6, 129.4, 127.7, 126.9,
126.5, 124.1, 118.7, 101.5, 78.5 (CHºC), 75.0 (CHºC),
55.9 (OCH2).
Compound 3c
Yieled: 96.0%; m.p. 242-243 °C; IR (KBr) n (cm-1):
3480 (NH), 1685 (C=O), 3082, 2931 (CH3), 1273 (C-O);
HR MS m/z: 450.1773 [M + H]+, (calculated for
C23H24N5O5 450.1777); 1H NMR (DMSO) d: 11.38 (s, 1H,
-NH), 8.50 (s, 1H, =CH), 7.85 (m, 3H), 7.84 (s, 1H), 7.53
(s, 1H), 7.50 (t, J = 7.2 Hz, 1H), 7.38 (t, J = 7.2 Hz, 1H),
7.22 (d, J = 7.6 Hz, 1H), 6.47 (t, J = 6.4 Hz, 1H), 5.43 (m,
1H), 5.33 (m, 1H), 5.29 (s, 2H), 4.26 (m, 1H), 3.68 (m, 2H),
2.72 (m, 2H), 1.82 (s, 3H, CH3); 13C NMR (DMSO) d:
164.2 (C=O), 156.4 (C=O), 150.9, 143.3, 136.7, 134.6,
129.8, 129.1, 127.9, 127.2, 126.9, 127.8, 119.1, 110.1,
107.6, 84.9, 84.3, 61.6, 61.2, 59.8, 37.6, 12.7 (CH3).
Compound 3d
Yieled: 95.0%; m.p. 245-246 °C; IR (KBr) n (cm-1):
3442 (NH), 1697 (C=O), 3082, 2934 (CH3), 1270 (C-O);
HR MS m/z: 450.1775 [M + H]+, (calculated for C23H24N5O5
450.1777); 1H NMR (DMSO) d: 11.37 (s, 1H, -NH), 8.55
(s, 1H, =CH), 8.15 (d, J = 8.0 Hz, 1H), 7.88 (d, J = 8.0 Hz,
1H), 7.83 (s, 1H, 6-H), 7.48 (m, 4H), 7.20 (d, J = 7.2 Hz,
1H), 6.47 (t, J = 6.4 Hz, 1H), 5.42 (m, 1H), 5.36 (s, 2H),
5.30 (m, 1H), 4.26 (m, 1H), 3.67 (m, 2H), 2.72 (m, 2H),
1.81 (s, 3H, CH3); 13C NMR (DMSO) d: 164.2 (C=O),
Compound 2e
1
Yellow solid, yield: 96.0%; H NMR (DMSO) d:
12.81 (s, 1H, OH), 8.06-8.08 (m, 2H), 7.55-7.62 (m, 3H),
7.03 (s, 1H), 6.84 (d, J = 1.6 Hz, 1H), 6.44 (d, J = 1.6 Hz,
1H), 4.95 (s, 2H, OCH2), 3.68 (s, 1H, ºCH); 13C NMR
(DMSO) d: 182.6 (C=O), 164.0, 163.6, 161.6, 157.6,
132.6, 130.9, 129.6, 126.9, 105.8, 105.7, 99.2, 94.2, 79.5
(CHºC), 78.8 (CHºC), 56.7 (OCH2).
3¢-Azido-2¢-deoxythymine (0.134 g, 0.5 mmol) and
the corresponding aryl propargyl ether (2a-e) (0.5 mmol)
were dissolved in t-BuOH/H2O (2 mL/2 mL) co-solvent.
The reaction mixture was stirred at room temperature for
10 min, and then added CuSO4·5H2O (0.006 g, 0.025
mmol) and L-ascorbic acid sodium (0.011 g, 0.05 mmol).
The reaction mixture was stirred at room temperature until
the starting material was consumed as judged by TLC anal-
ysis. A white precipitate was generated when the reaction
was over. The precipitate was filtered, washed with ice-
cold water and dried, and the white solids (3a-e) were
obtianed.

Mono and Bis-1,2,3-triazole AZT Derivatives
J. Chin. Chem. Soc., Vol. 58, No. 1, 2011 29
153.9 (C=O), 150.9, 143.6, 136.7, 134.5, 127.9, 126.9,
126.6, 125.8, 125.3, 124.6, 122.0, 120.8, 110.1, 106.3,
84.9, 84.3, 62.2, 61.2, 59.7, 37.6, 12.7 (CH3).
Compound 6a
Yieled: 95.0%; m.p. 198-199 °C; IR (KBr) n (cm-1):
3491 (NH), 1676 (C=O), 3082, 2934 (CH3), 1275 (C-O);
HR MS m/z: 743.2510 [M + Na]+, (calculated for
C32H36N10O10Na 743.2514); 1H NMR (DMSO) d: 11.38 (s,
2H, -NH), 8.42 (s, 2H, =CH), 7.83 (s, 2H, =CHN), 6.95 (s,
4H), 6.45 (t, J = 6.4 Hz, 2H), 5.40 (m, 2H), 5.30 (m, 2H),
5.10 (s, 4H), 4.23 (m, 2H), 3.65 (m, 4H), 2.70 (m, 4H), 1.81
(s, 6H, -CH3); 13C NMR (DMSO) d: 164.2 (C=O), 152.8,
150.9 (C=O), 143.6, 136.7, 124.6, 116.0, 110.1, 84.9, 84.3,
61.9, 61.2, 59.7, 37.6, 12.7 (-CH3).
Compound 3e
Yieled: 72.0%; m.p. 223-224 °C; IR (KBr) n (cm-1):
3418 (NH), 1697 (C=O), 3080, 2930 (CH3), 1272 (C-O);
HR MS m/z: 582.1598 [M + Na]+, (calculated for
C28H254N5O8Na 582.1601); 1H NMR (DMSO) d: 12.84 (s,
1H, -OH), 11.36 (s, 1H, -NH), 8.49 (s, 1H, =CH), 8.12 (d, J
= 7.2 Hz, 2H), 7.82 (s, 1H, 6-H), 7.62 (m, 3H), 7.07 (s, 1H),
6.99 (d, J = 2.0 Hz, 1H), 6.53 (d, J = 1.6 Hz, 1H), 6.45 (t, J =
6.4 Hz, 1H), 5.38 (m, 1H), 5.30 (s, 2H), 5.29 (t, J = 4.2 Hz,
1H), 4.25 (m, 1H), 3.54 (m, 2H), 2.72 (m, 2H), 1.81 (s, 3H,
CH3); 13C NMR (DMSO) d: 182.6 (C=O), 164.5 (C=O),
164.2 (C=O), 164.0, 161.7, 157.8, 150.9, 142.5, 136.7,
132.7, 131.1, 129.6, 126.9, 125.1, 110.1, 105.9, 105.6,
99.2, 94.1, 84.9, 84.4, 62.3, 61.2, 59.8, 37.6, 12.7 (CH3).
Synthesis of bis-1,2,3-triazoles AZT derivatives (6a-c)
Synthesis of bis(ethynyloxy)benzene (5a-c) was
same as that of 2a-e.
Compound 6b
Yieled: 93.0%; m.p. 194-195 °C; IR (KBr) n (cm-1):
3480 (NH), 1710 (C=O), 3078, 2940 (CH3), 1255 (C-O);
HR MS m/z: 743.2508 [M + Na]+, (calculated for
C32H36N10O10Na 743.2514); 1H NMR (DMSO) d: 11.38 (s,
2H, -NH), 8.45 (s, 2H, =CH), 7.83 (s, 2H, =CHN), 7.25 (t, J
= 8.0 Hz, 1H), 6.75 (s, 1H), 6.68 (m, 2H), 6.45 (t, J = 6.4
Hz, 2H), 5.41 (m, 2H), 5.34 (m, 2H), 5.15 (s, 4H), 4.23 (m,
2H), 3.67 (m, 4H), 2.72 (m, 4H), 1.82 (s, 6H, -CH3); 13
C
Compound 5a
NMR (DMSO) d: 164.2 (C=O), 159.7, 150.9 (C=O), 143.3,
136.7, 130.5, 124.7, 110.1, 107.7, 102.0, 84.9, 84.3, 61.5,
61.2, 59.7, 37.6, 12.7 (-CH3).
Brown solid, yield: 96.0%; 1H NMR (CDCl3) d: 6.93
(s, 4H), 4.65 (d, J = 2.4 Hz, 4H, OCH2), 2.51 (t, J = 2.4 Hz,
2H, ºCH); 13C NMR (CDCl3) d: 152.4 (O-C), 116.0, 78.8
(CHºC), 75.4 (CHºC), 56.5 (OCH2).
Compound 6c
Yieled: 92.0%; m.p. 197-198 °C; IR (KBr) n (cm-1):
3437 (NH), 1696 (C=O), 3085, 2931 (CH3), 1274 (C-O);
HR MS m/z: 743.2520 [M + Na]+, (calculated for
C32H36N10O10Na 743.2514); 1H NMR (DMSO) d: 11.36 (s,
2H, -NH), 8.39 (s, 2H, =CH), 7.81 (s, 2H, =CHN), 7.18 (q,
J = 5.6 Hz, 2H), 6.93 (q, J = 5.6 Hz, 2H), 6.43 (t, J = 6.4 Hz,
2H), 5.37 (m, 2H), 5.28 (t, J = 5.2 Hz, 2H), 5.14 (s, 4H),
4.21 (m, 2H), 3.64 (m, 4H), 2.68 (m, 4H), 1.79 (s, 6H,
-CH3); 13C NMR (DMSO) d: 164.2 (C=O), 150.9 (C=O),
148.3, 143.5, 136.7, 124.8, 121.9, 114.9, 110.1, 84.9, 84.3,
62.2, 61.2, 59.7, 37.6, 12.7 (-CH3).
Compound 5b
Colorless liquid, yield: 95.0%; 1H NMR (CDCl3) d:
7.23 (m, 1H), 6.64 (m, 3H), 4.74 (s, 4H, OCH2), 2.53 (s,
2H, ºCH); 13C NMR (CDCl3) d: 147.6 (O-C), 122.2, 115.0,
102.0, 78.7 (CHºC), 75.9 (CHºC), 56.8 (OCH2).
Compound 5c
Colorless liquid, yield: 96.0%; 1H NMR (CDCl3) d:
6.88 (m, 2H), 6.77 (m, 2H), 4.56 (d, J = 2.4 Hz, 4H), 2.42 (t,
J = 2.4 Hz, 2H); 13C NMR (CDCl3) d: 147.5 (O-C), 121.8,
115.0, 78.4 (CHºC), 75.6 (CHºC), 56.5 (OCH2).
3¢-Azido-2¢-deoxythymine (0.134 g, 0.5 mmol) and
the corresponding bis(ethynyloxy) benzene (5a-c) (0.5
mmol) were dissolved in t-BuOH/H2O (4 mL/4 mL) co-sol-
vent. The mixture was stirred for 10 min at room tempera-
ture, and added CuSO4·5H2O (0.012 g, 0.05 mmol) and
L-ascorbic acid sodium (0.022 g, 0.1 mmol). The resulting
reaction mixture was stirred at room temperature until the
material was consumed as monitored by TLC. Aprecipitate
was generated when the reaction was over. After washing
with ice-cold water and dried, the products (6a-c) were
obtained.
ACKNOWLEDGEMENT
The authors would like to thank the National Natural
Science Foundation of China (No. 20472076 and 21072178)
and Innovation Specialist Projects of Henan Province for
their financial support.
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