Copper-catalyzed click synthesis of functionalized 1,2,3-triazoles with 3,4-dihydropyrimidinone or amide group via a one-pot four-component reaction

Article abstract of DOI:10.1016/j.tet.2012.10.097

A Cu (I) generated in situ from Cu(OAc)₂·H ₂O/sodium ascorbate catalyzed one-pot multicomponent reaction for the synthesis of a series of N-functionalized 1,2,3-triazoles with 3,4-dihydropyrimidione from 3,4-dihydropyrimidiones, paraformaldehyde, sodium azide and alkynes is described. Remarkably N-functionalized 1,2,3-triazoles with amide were prepared by this method. This procedure eliminates the need to handle organic halides or organic azides, as they are generated in situ, making this already powerful click process even more user-friendly and safe.

Full text of DOI:10.1016/j.tet.2012.10.097

Tetrahedron 69 (2013) 881e887
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Copper-catalyzed click synthesis of functionalized 1,2,3-triazoles
with 3,4-dihydropyrimidinone or amide group via a one-pot
four-component reaction
,
b
,
a
,
,
,
,b,
Zheng-Jun Quan a , Qiong Xu b, Zhang Zhang a b, Yu-Xia Da a b, Xi-Cun Wang a
*
*
a Key Laboratory of Eco-Environment-Related Polymer Materials, Ministry of Education, China, Gansu 730070, PR China
b Gansu Key Laboratory of Polymer Materials, College of Chemistry and Chemical Engineering, Northwest Normal University, Anning East Road 967#, Lanzhou,
Gansu 730070, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 3 July 2012
Received in revised form
28 September 2012
Accepted 9 October 2012
Available online 8 November 2012
A Cu (I) generated in situ from Cu(OAc)2$H2O/sodium ascorbate catalyzed one-pot multicomponent
reaction for the synthesis of a series of N-functionalized 1,2,3-triazoles with 3,4-dihydropyrimidione
from 3,4-dihydropyrimidiones, paraformaldehyde, sodium azide and alkynes is described. Remarkably
N-functionalized 1,2,3-triazoles with amide were prepared by this method. This procedure eliminates the
need to handle organic halides or organic azides, as they are generated in situ, making this already
powerful click process even more user-friendly and safe.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
1,2,3-Triazoles
Cu (I)-catalyzed azideealkyl cycloadition
N3-substituted dihydropyrimidinones
Amides
1. Introduction
problematic due to their potential explosive or unstable nature. For
example, three-component copper catalyzed reactions in which
Multicomponent reactions (MCRs) were increasingly important
in organic and medicinal chemistry, because they offered significant
advantages over conventional linear-type syntheses.1 For example,
MCRs themselves were chemo- and regioselective, convergent step-
efficient procedures and took place with high atom economy.2
Another important feature implied the diminution of waste
production due to the decrease of synthetic or isolation steps along
with saving time.3
Since copper (I)-catalyzed azideealkyne cycloaddition (CuAAC)
was reported independently by the groups of Sharpless and Meldal
in 2002.4 It proceeded highly regioselectively when using terminal
alkynes, thereby lead to exclusively 1,4-disubstituted 1,2,3-triazoles
as the sole products. The N-heterocyclic compound of 1,2,3-
triazoles has rapidly become one of the most popular structures
owing to their diverse uses, ranging from medicinal,5 material,6 to
biological7 research. Recent efforts have been aimed at the in-
vestigation of the chemical and biological properties of this unique
heterocycle.8 A few methods were designed to circumvent the
handling of azides, whose synthesis and isolation can be
azides were generated in situ from corresponding alkyl or aryl
halides and sodium azide in the presence of terminal alkynes gave
access to diversely substituted 1,2,3-triazoles.9
3,4-Dihydropyrimidinones (DHPMs) have attracted consider-
able interest due to their interesting pharmacological properties,
such as calcium channel modulator, antihypertensive, a1a-adren-
ergic agonists mitotic kinesin inhibitor and hepatitis B virus repli-
cation suppressor.10 Among DHPM derivatives, most of the
pharmacologically attractive forms are N3-substituted analogues.11
For example, N3-functionalized 4-aryl-3,4-dihydropy rimidine-2
(1H)-ones exhibited a broad range of biological effects11b and
have recently appeared as, e.g., antihypertensive agents SQ32547,
SQ32926 and a1a-adrenergic receptor antagonists.12
We recently reported
a regioselective synthesis of the
N3-functionalized DHPMs by reaction of DHPMs with para-
formaldehyde and various reagents in the presence of trimethyl
chlorosilicane (TMSCl).13 In the context, we became interested
in combining click chemistry (azideeacetylene cycloadditions)
with MCR strategies. Herein, we reported an efficient app-
roach for the one-pot synthesis of libraries including both 3,4-
dihydropyrimidinones/amides and 1,2,3-triazole rings in their
structures.
* Corresponding authors. Tel./fax: þ86 931 7971971; e-mail addresses: quanzhen
gjun@hotmail.com (Z.-J. Quan), wangxicun@nwnu.edu.cn (X.-C. Wang).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.10.097

882
Z.-J. Quan et al. / Tetrahedron 69 (2013) 881e887
2. Results and discussion
ineffective and most starting materials (2) were recovered (entry
4). Improved yields were obtained when Cu(OAc)2$H2O/NaAsc and
CuSO4$5H2O/NaAsc were screened (entries 5 and 6). The reaction
was obviously enhanced by addition of Et3N (entries 7e8). Thus we
used Cu(OAc)2$H2O/NaAsc as the optimal catalyst system.
Initially, the desired products 4aed were synthesized via the
1,3-dipolar cycloaddition between N3-azide functionalized DHPMs
2aed, which can be conveniently prepared according to our reported
process,13 with phenylacetylene 3a using water as the reaction
medium in the presence of 10 mol % of CuI (Scheme 1).
With the optimized conditions in hand, we used DHPMs and
diverse set of alkynes to test the reaction scope. In general, good to
excellent yields were obtained under the standard reaction con-
ditions. Therefore, a variety of triazoles 4 were obtained (Table 2),
displaying both electron-rich (entries 1e4) as well as functional-
ized electron-deficient (entries 5 and 6) aryl-substituents of
DHPMs, while o-chloro group on the phenyl ring give a slightly
lower yield (entry 5). Sulfur-containing analogues of DHPMs 1
exhibited a slightly lower reactivity, the yields of the desired
products decreased about 20% (entries 9 and 10). The structures of
the final product 4d were characterized by X-ray crystallographic
analysis (Fig. 1).14 Good to moderate yields of desired 1,2,3-triazole
derivatives were obtained employing terminal alkynes with dif-
ferent groups, including alkyl and aryl alkynes (entries 11e15).
Quinazolinones 5 were also exposed to the standard reaction
conditions, resulting in the formation of N-functionalized quina-
zolinones with 1,2,3-triazole derivatives 6aec (Scheme 3). It is
noteworthy that this four-component one-pot synthesis involved
the formation of three CeN bonds in a highly selective fashion. It
was obvious that the one-pot method didn’t need the separation of
organic azides and had greater advantages due to simplifying the
experimental procedure.
O
Ar
O
Ar
N
N
EtO
Me
N
N3
EtO
Me
N
N
CuI
Ph
+
Ph
water, rt, 6h
N
H
O
N
H
O
3a
4a-d
2a-d
Ar = Ph (2a, 4a), 4-MeC6H4 (2b, 4b)
Ar = 4-ClC6H4 (2c, 4c), 4-MeOC6H4 (2d, 4d)
4a: 64 %, 4b: 68 %
4c: 62 %, 4d: 66 %
Scheme 1. Fractional-step synthesis of triazoles using N3-azide functionalized DHPMs.
Then, we moved to the development of the one-pot three-step
version of this transformation. By heating the mixture of DHPM 1
with paraformaldehyde in the presence of TMSCl in dichloro-
methane (DCM) at 35 ꢀC for 24 h and subsequently adding NaN3 for
another 12 h gave the intermediate 2. Without isolation of the
compound 2, then phenylacetylene 3a, triethylamine (Et3N) and
10 mol % CuI were added to the reaction mixture and the mixture
was stirred at refluxing for another 1.5 h giving the cycloaddition
products 4aed in a total yields of 67e72% (Scheme 2).
O
Ar
O
Ar
i) (CH2O)n, TMSCl
DCM, 35 °C, 24 h
N
N
EtO
Me
N
N
EtO
Me
NH
3a
Ph
Ph
N
H
4
O
ii) NaN3
CuI, Et3N, 35 °C, 1.5 h
N
H
O
DCM, 35 °C, 12 h
1
4a: 67 %, 4b: 70 %
4c: 67 %, 4d: 72 %
Ar = Ph (1a, 4a), 4-MeC6H4 (1b, 4b)
Ar = 4-ClC6H4 (1c, 4c), 4-MeOC6H4 (1d, 4d)
Scheme 2. One-pot three-step synthesis of triazoles from DHPMs.
Subsequently, we probed a modular synthesis of triazoles 4
through a click chemistry of four components by a one-pot two-
step method. Treatment the DHMP 1a with paraformaldehyde and
TMSCl in DCM at 35 ꢀC for 12 h and subsequently adding NaN3 and
phenylacetylene 3a for another 8 h gave the product 4a. Various
copper salts were tested, Cu (I) salts, for example, CuCl, CuBr and
CuI all gave good yields (Table 1, entries 1e3). Cu(OAc)2$H2O was
To explore the scope of differentiated substrates in the one-
pot two-step reaction, extensive amides 7 were exposed to the
standard reaction conditions at rt, resulting in the formation of
1,2,3-triazole products 8aee (Table 3). As depicted in Table 3,
all the two-step reactions can be carried out at room temper-
ature (rt) within shorter reaction times (total 12 h) and good
yields of azideealkyne cycloaddition products were obtained.
Table 1
Optimization of the sequential azideealkyne cycloadditiona
O
Ph
O
Ph
N
N
a) (CH2O)n, TMSCl
DCM, 35 °C, 12 h
b) NaN3,
conditions
Ph 3a EtO
Me
N
N
EtO
Me
NH
Ph
N
O
N
H
O
H
4a
1a
Entry
Catalysts (mol %)
Base
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
CuI (10)
CuBr (10)
CuCl (10)
Cu(OAc)2$H2O (20)
Cu(OAc)2$H2O (20)/NaAsc (40)
CuSO4$5H2O (20)/NaAsc (40)
Cu(OAc)2$H2O (20)/NaAsc (40)
Cu(OAc)2$H2O (20)
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
d
8
8
8
8
8
8
12
12
73
72
70
48
76
73
10
5
d
a
Reaction conditions: the compound 2a was prepared to our previous procedure and not isolated. DHPM (1a, 0.5 mmol), phenylacetylene (3a, 0.6 mmol), triethylamine
(1 mmol), catalyst, 35 ꢀC.
b
Isolated yields.

Z.-J. Quan et al. / Tetrahedron 69 (2013) 881e887
883
Table 2
Sequential copper-catalyzed synthesis functionalized 1,2,3-triazolesa
Ar
O
Ar
O
a ) (CH2O)n , TMSCl, DCM, 35 °C, 12 h
N
N
N
EtO
Me
NH
EtO
Me
N
b) NaN3,
R, Et3N
R
N
H
X
Cu(OAc)2·H2O/NaAsc, 35 °C, 8 h
N
H
X
1
4
Entry
Ar
Ph
R
X
Product
Yield (%)b
1
2
3
4
5
6
7
8
Phenyl
Phenyl
Phenyl
Phenyl
Phenyl
Phenyl
Phenyl
Phenyl
Phenyl
Phenyl
Pentyl
Pentyl
(4-Nitrophenoxy)methyl
(4-Nitrophenoxy)methyl
(4-Formylphenoxy)methyl
O
O
O
O
O
O
O
O
S
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
76
73
72
68
65
72
75
72
57
56
73
70
73
71
69
4-MeC6H4
4-ClC6H4
4-NO2C6H4
2-ClC6H4
4-MeOC6H4
4-BrC6H4
4-FC6H4
4-MeC6H4
4-MeOC6H4
Ph
9
10
11
12
13
14
15
S
O
O
O
O
O
4-MeC6H4
4-MeC6H4
4-MeOC6H4
Ph
a
One-pot reaction conditions: (a) DHPMs (0.5 mmol), paraformaldehyde (2 mmol), TMSCl (1.25 mmol), DCM (5 mL), 35 ꢀC, 12 h; (b) NaN3 (1 mmol), alkynes (0.6 mmol),
Cu(OAc)2$H2O (0.1 mmol)/NaAsc (0.2 mmol), Et3N (1 mmol), 35 ꢀC, 8 h.
b
Isolated yields of the one-pot method.
they are generated in situ, making this already powerful click
process even more user-friendly and safe.
4. Experimental section
4.1. General
Melting points were determined on an XT-4 electrothermal
micromelting point apparatus and uncorrected. NMR spectra were
recorded at 400 (1H) and 100 (13C) MHz, respectively, on a Varian
Mercury plus-400 instrument using CDCl3 and DMSO-d6 as solvent
and TMS as internal standard. IR spectra were obtained using an
Alpha centauri FTIR spectrophotometer and only major peaks were
reported in cmꢁ1. Mass-spectra were recorded on a TRACE DSQ
instrument. Elemental analyses were performed on a Carlo-Erba
1106 Elemental Analysis instrument. TLC was performed on
Fig. 1. X-ray crystal structure of 4d.
5ꢂ10 cm aluminium plates coated with silica gel 60F-254 in an
The unsaturated N-methylcinnamamide was also well tolerated
(entry 2), as substituted N-methylbenzamide and N-methyl-2-
phenoxyacetamide (entries 3e5).
appropriate solvent. All reagents were obtained commercially and
used without further purification.
3. Conclusion
4.2. General procedure for the synthesis of N3-functionalized
pyrimidines with 1,2,3-triazole 4
In summary, we have developed a one-pot two-step protocol for
the synthesis of a series of functionalized 1,2,3-triazoles derivatives
in good yields. Especially, N-functionalized 1,2,3-triazoles with
amide or DHPM were prepared by this method. This procedure
eliminates the need to handle organic halides or organic azides, as
The mixture of 3,4-dihydropyrimidinone (0.5 mmol), para-
formaldehyde (2 mmol) and trimethyl chlorosilicane (1.5 mmol) in
CH2Cl2 (5 mL) was stirred vigorously for 12 h at 35 ꢀC. Then, sodium
azide (1 mmol), acetylene (0.6 mmol), triethylamine (1 mmol),
O
Ar
O
Ar
N
a) (CH2O)n, TMSCl, dioxane, 35 °C, 12 h
N
NH
N
N
b) NaN3,
Cu(OAc)2 H2O/NaAsc, 35 °C, 8 h
R, Et3N
R
N
H
O
N
H
O
5
6
Ar = Ph; R = Ph (5a, 6a) Ar = Ph; R = 4-NO2C6H4OCH2 (5b, 6b)
Ar = 4-MeC6H4; R = 4-NO2C6H4OCH2 (5c, 6c)
6b: 70%
6a: 73%
6c: 71%
Scheme 3. One-pot two-step synthesis of functional triazoles from quinazolinones.

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Z.-J. Quan et al. / Tetrahedron 69 (2013) 881e887
Table 3
Sequential synthesis of N-functionalized 1,2,3-triazoles with amide
O
O
Ph
a ) (CH2O)n, TMSCl, DCM, rt, 4 h
b) NaN3,
Et3N
Cu(OAc)2
R1
N
H
R1
N
N
N
Ph,
H2O/NaAsc, rt, 8 h
N
7
8
•
Entry
1
Material
Product
Yielda (%)
78
7a
8a
2
3
4
69
73
72
7b
7c
8b
8c
7d
7e
8d
8e
5
71
a
Isolated yield under the reaction condition: (a) amides (0.5 mmol), paraformaldehyde (2 mmol), TMSCl (1.25 mmol), DCM (5 mL), rt, 4 h; (b) NaN3 (1 mmol), alkynes
(0.6 mmol), Cu(OAc)2$H2O (0.1 mmol)/NaAsc (0.2 mmol), Et3N (1 mmol), rt, 8 h.
Cu(OAc)2$H2O (0.01 mmol) and sodium ascorbate (0.02 mmol) were
added into the mixture. After completion monitored by TLC, the re-
action mixture was quenched into 15 mL of saturated aqueous NH4Cl
solution, mixedandseparated.Theaqueousphasewasextractedwith
3ꢂ15 mL of CH2Cl2 and the combined organic phases were dried over
Na2SO4 and concentrated. The products were separated by silica gel
column chromatography eluted with ethyl acetate/petroleum ether.
For the analogous reaction of theN-methyl carbamate7(0.5mmol),
thereactionwasperformedatrtfor4h(firststep)and8h(secondstep)
giving the products 8.
(s, 1H, CH), 7.79 (d, J¼8.4 Hz, 2H, ArH), 7.44e7.30 (m, 5H, ArH), 7.11
(d, J¼8 Hz, 2H, ArH), 6.10 (d, J¼14 Hz, 1H, CH2), 5.53 (d, J¼14 Hz, 1H,
CH2), 5.52 (s, 1H, CH), 4.06e4.01 (m, 2H, CH2), 2.37 (s, 3H, CH3), 2.27
(s, 3H, CH3), 1.16 (t, J¼7.2 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3)
d
¼164.82, 152.58, 148.39, 144.55, 138.37, 137.68, 130.24, 129.39,
128.78, 128.23, 127.55, 125.70, 120.09, 102.86, 60.23, 60.09, 57.73,
21.06,18.44,14.04; IR (KBr): 3223, 3104, 2984,1708, 1686, 1641, 1460,
1248, 1084, 768 cmꢁ1; EI-MS m/z: 431 (Mþ), 285 (100%); Anal. Calcd
for C24H25N5O3 (431.19): C, 66.81; H, 5.58; N, 16.23. Found: C, 66.88;
H, 5.57; N, 16.19.
4.2.1. Ethyl 6-methyl-2-oxo-4-phenyl-3-[(4-phenyl-1H-1,2,3-triazol-
1-yl)methyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate (4a). White
solid, mp 210e212 ꢀC; yield: 76% (ethyl acetate/petroleum ether:
4.2.3. Ethyl 6-methyl-2-oxo-4-(4-chlorophenyl)-3-[(4-phenyl-1H-1,2,
3-triazol-1-yl)methyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate
(4c). White solid, mp 208e210 ꢀC; yield: 72% (ethyl acetate/petro-
1/3); 1H NMR (400 MHz, CDCl3)
d
¼7.95 (s, 1H, CH), 7.80 (d, J¼8.8 Hz,
leum ether: 1/3); 1H NMR (400 MHz, CDCl3)
d¼7.94 (s, 1H, CH), 7.79
2H, ArH), 7.44 (br s,1H, NH), 7.42e7.26 (m, 8H, ArH), 6.13 (d, J¼14 Hz,
1H, CH2), 5.57 (s, 1H, CH), 5.48 (d, J¼14 Hz, 1H, CH2), 4.06e4.01 (m,
2H, CH2), 2.36 (s, 3H, CH3), 1.15 (t, J¼7.2 Hz, 3H, CH3); 13C NMR
(d, J¼7.2 Hz, 2H, ArH), 7.59 (s, 1H, NH), 7.44e7.28 (m, 7H, ArH), 6.12
(d, J¼14 Hz, 1H, CH2), 5.55 (s, 1H, CH), 5.48 (d, J¼14 Hz, 1H, CH2),
4.12e3.98 (m, 2H, CH2), 2.36 (s, 3H, CH3), 1.16 (t, J¼7.2 Hz, 3H, CH3);
(100 MHz, CDCl3)
d
¼164.75, 152.33, 148.44, 144.63, 140.58, 130.23,
13C NMR (100 MHz, CDCl3)
d
¼164.54, 152.02, 148.60, 144.74, 139.09,
128.80, 128.77, 128.54, 128.28, 127.71, 125.74, 120.16, 102.74, 60.33,
60.27, 57.64, 18.51, 14.03; IR (KBr): 3218, 3102, 2965, 1708, 1687, 1632,
1456, 1241, 1082, 801 cmꢁ1; EI-MS m/z: 417 (Mþ), 271 (100%); Anal.
Calcd for C23H23N5O3 (417.18): C, 66.17; H, 5.55; N, 16.78. Found: C,
66.25; H, 5.47; N, 16.80.
134.43, 130.10, 129.08, 128.95, 128.84, 128.37, 125.75, 120.11, 102.11,
60.42, 59.67, 57.58, 18.62, 14.07; IR (KBr): 3236, 3122, 2978, 1702,
1681, 1654, 1456, 1261, 1086, 766 cmꢁ1; EI-MS m/z: 453 (Mþþ2), 451
(Mþ), 305 (100%); Anal. Calcd for C23H22ClN5O3 (451.14): C, 61.13; H,
4.91; N, 15.50. Found: C, 61.21; H, 4.81; N, 16.01.
4.2.2. Ethyl 6-methyl-2-oxo-4-(4-methylphenyl)-3-[(4-phenyl-1H-1,2,
3-triazol-1-yl)methyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate
(4b). White solid, mp 204e206 ꢀC; yield: 73% (ethyl acetate/petro-
4.2.4. Ethyl 6-methyl-2-oxo-4-(4-nitrophenyl)-3-[(4-phenyl-1H-1,2,
3-triazol-1-yl)methyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate
(4d). White solid, mp 243e244 ꢀC; yield: 68% (ethyl acetate/petro-
leum ether: 1/2); 1H NMR (400 MHz, CDCl3)
d¼8.09 (s, 1H, NH), 7.90
leum ether: 1/3); 1H NMR (400 MHz, CDCl3)
d¼8.14 (d, J¼8.8 Hz, 2H,

Z.-J. Quan et al. / Tetrahedron 69 (2013) 881e887
885
ArH), 7.92 (s, 1H, CH), 7.73 (d, J¼8.4 Hz, 2H, ArH), 7.67 (s, 1H, NH),
7.43e7.32 (m, 5H, ArH), 6.08 (d, J¼14 Hz, 1H, CH2), 5.70 (s,1H, CH), 5.61
(d, J¼14 Hz, 1H, CH2), 4.10e4.06 (m, 2H, CH2), 2.39 (s, 3H, CH3), 1.19
Calcd for C23H22FN5O3 (435.17): C, 63.44; H, 5.09; N, 16.08. Found:
C, 63.59; H, 4.98; N, 16.29.
(t, J¼7.2Hz, 3H, CH3);13C NMR (100 MHz, DMSO-d6)
d¼164.46, 151.30,
4.2.9. Ethyl 6-methyl-1-[(4-phenyl-1H-1,2,3-triazol-1-yl)methyl]-2-
thioxo-4-p-tolyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate
(4i). White solid, mp 134e136 ꢀC; yield: 57% (ethyl acetate/petro-
148.86, 147.72, 146.80, 146.75, 130.24, 128.84, 128.13, 128.02, 125.26,
123.70,121.34,100.20, 59.81, 59.04, 58.80,17.65,14.06; IR (KBr): 3224,
3130, 2988, 1699,1672, 1641, 1448, 1344, 1244,1117, 769 cmꢁ1; EI-MS
m/z: 462 (Mþ), 300 (100%); Anal. Calcd for C23H22N6O5 (462.16):
C, 59.73; H, 4.79; N, 18.17. Found: C, 59.81; H, 4.70; N, 18.26.
leum ether: 1/6); 1H NMR (400 MHz, CDCl3)
d¼8.26 (s, 1H, CH), 7.81
(s, 1H, NH), 7.80 (d, J¼8.4 Hz, 2H, ArH), 7.44e7.27 (m, 5H, ArH), 7.12
(d, J¼8.4 Hz, 2H, ArH), 6.82 (d, J¼14 Hz, 1H, CH2), 5.92 (d, J¼14 Hz,
1H, CH2), 5.67 (s, 1H, CH), 4.13e4.02 (m, 2H, CH2), 2.34 (s, 3H, CH3),
2.26 (s, 3H, CH3), 1.19 (t, J¼7.2 Hz, 3H, CH3); 13C NMR (100 MHz,
4.2.5. Ethyl 6-methyl-2-oxo-4-(2-chlorophenyl)-3-[(4-phenyl-1H-1,2,
3-triazol-1-yl)methyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate
(4e). White solid, mp 201e203 ꢀC; yield: 65% (ethyl acetate/petro-
CDCl3)
d
¼176.64, 164.43, 148.19, 140.90, 138.80, 136.97, 130.17,
129.56, 128.77, 128.26, 127.53, 125.79, 120.61, 104.40, 62.44, 60.59,
60.23, 21.07, 18.12, 14.05; IR (KBr): 3126, 3097, 2923, 1703, 1679,
1647, 1535, 1454, 1240, 1159, 1095, 763 cmꢁ1; EI-MS m/z: 447 (Mþ),
302 (100%); Anal. Calcd for C24H25N5O2S (447.17): C, 64.41; H, 5.63;
N, 15.65. Found: C, 64.53; H, 5.57; N, 15.78.
leum ether: 1/3); 1H NMR (400 MHz, CDCl3)
d¼7.99 (s, 1H, NH), 7.96
(s, 1H, CH), 7.80 (d, J¼8.4 Hz, 2H, ArH), 7.51 (d, J¼6.8 Hz, 1H, ArH),
7.42 (t, J¼8 Hz, 2H, ArH), 7.38e7.22 (m, 5H, ArH), 6.15 (s, 1H, CH),
6.09 (d, J¼14 Hz, 1H, CH2), 5.53 (d, J¼14 Hz, 1H, CH2), 4.05e3.98 (m,
2H, CH2), 2.39 (s, 3H, CH3), 1.12 (t, J¼7.2 Hz, 3H, CH3); 13C NMR
(100 MHz, CDCl3)
d
¼164.62, 152.02, 145.62, 145.64, 137.88, 133.13,
4.2.10. Ethyl 6-methyl-3-[(4-phenyl-1H-1,2,3-triazol-1-yl)methyl]-2-
thioxo-4-(methoxylphenyl)-1,2,3,4-tetrahydropyrimidine-5-
carboxylate (4j). White solid, mp 165e167 ꢀC; yield: 56% (ethyl ace-
130.77, 130.30, 130.12, 129.89, 128.79, 128.21, 127.55, 125.71, 120.20,
101.21, 60.30, 58.02, 57.90, 18.41, 13.98; IR (KBr): 3225, 3119, 2989,
1703, 1688, 1651, 1458, 1273, 1082, 792 cmꢁ1; EI-MS m/z: 453
(Mþþ2), 451 (Mþ), 305 (100%); Anal. Calcd for C23H22ClN5O3
(451.14): C, 61.13; H, 4.91; N, 15.50. Found: C, 61.21; H, 4.70; N, 15.89.
tate/petroleum ether: 1/6); 1H NMR (400 MHz, CDCl3)
d¼8.27 (s, 1H,
CH), 7.99 (s, 1H, NH), 7.80 (d, J¼7.2 Hz, 2H, ArH), 7.44e7.30 (m, 5H,
ArH), 6.85e6.82 (m, 3H, ArH, CH2), 5.92 (d, J¼14 Hz,1H, CH2), 5.65 (s,
1H, CH), 4.15e4.01 (m, 2H, CH2), 3.72(s, 3H, CH3), 2.35(s, 3H, CH3),1.18
4.2.6. Ethyl 6-methyl-2-oxo-4-(4-methoxylphenyl)-3-[(4-phenyl-1H-
1,2,3-triazol-1-yl)-methyl]-1,2,3,4-tetrahydropyrimidine-5-
carboxylate (4f). White solid, mp 190e192 ꢀC; yield: 72% (ethyl
(t, J¼7.6 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3)
¼176.51, 164.47,
d
159.86, 148.22, 140.83, 132.08, 130.15, 128.98, 128.78, 125.29, 125.80,
120.59,114.21, 104.47, 62.31, 60.56, 60.39,18.04,14.17, 14.05; IR (KBr):
acetate/petroleum ether: 1/3); 1H NMR (400 MHz, CDCl3)
d¼7.95 (s,
3124, 3095, 2956, 1708, 1689, 1652,1539, 1460,1244, 1161, 763 cmꢁ1
;
1H, NH), 7.92 (s, 1H, CH), 7.79 (d, J¼8.4 Hz, 2H, ArH), 7.44e7.31 (m,
5H, ArH), 6.83 (d, J¼8.4 Hz, 2H, ArH), 6.11 (d, J¼14 Hz, 1H, CH2), 5.53
(d, J¼14 Hz, 1H, CH2), 5.50 (s, 1H, CH), 4.11e3.96 (m, 2H, CH2), 3.73
(s, 3H, CH3), 2.37 (s, 3H, CH3), 1.16 (t, J¼7.2 Hz, 3H, CH3); 13C NMR
EI-MS m/z: 463 (Mþ), 333 (100%); Anal. Calcd for C24H25N5O3S
(463.17): C, 62.18; H, 5.44; N, 15.11. Found: C, 62.31; H, 5.35; N, 15.26.
4.2.11. Ethyl
6-methyl-2-oxo-3-[(4-pentyl-1H-1,2,3-triazol-1-yl)
(100 MHz, CDCl3)
d
¼164.83, 159.61, 152.40, 148.43, 144.29, 132.74,
methyl]-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate
(4k). White solid, mp 131e133 ꢀC; yield: 73% (ethyl acetate/petro-
130.22, 128.94, 128.79, 128.26, 125.71, 120.08, 114.03, 102.96, 60.23,
59.76, 57.59, 55.20, 18.46, 14.06; IR (KBr): 3214, 3094, 2956, 1707,
1686, 1638, 1461, 1242, 1086, 772 cmꢁ1; EI-MS m/z: 447 (Mþ), 301
(100%); Anal. Calcd for C24H25N5O4 (447.19): C, 64.42; H, 5.63; N,
15.65. Found: C, 64.53; H, 5.59; N, 15.73.
leum ether: 1/4); 1H NMR (400 MHz, CDCl3)
d¼8.54 (s, 1H, NH), 7.44
(s,1H, CH), 7.42e7.28 (m, 5H, ArH), 6.04 (d, J¼14 Hz,1H, CH2), 5.51 (s,
1H, CH), 5.43 (d, J¼13.6 Hz,1H, CH2), 4.09e3.99 (m, 2H, CH2), 2.66 (t,
J¼7.6Hz, 2H, CH2), 2.38 (s, 3H, CH3),1.67e1.60 (m, 2H, CH2),1.37e1.31
(m, 4H, eCH2CH2e), 1.15 (t, J¼7.2 Hz, 3H, CH3), 0.90 (t, J¼7.6 Hz, 3H,
4.2.7. Ethyl 6-methyl-2-oxo-4-(4-bromophenyl)-3-[(4-phenyl-1H-1,2,
3-triazol-1-yl)-methyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate
(4g). White solid, mp 201e203 ꢀC; yield: 75% (ethyl acetate/petro-
CH3); 13C NMR (100 MHz, CDCl3)
d
¼164.89, 152.57, 149.18, 144.66,
138.22,137.76,129.35,127.57,121.02,102.80, 60.19, 59.87, 57.38, 31.47,
28.96, 25.59, 22.38, 21.13, 18.40, 14.04, 13.98; IR (KBr): 3230, 3101,
3028, 2958, 1712,1682, 1639, 1472, 1240, 1085, 761, 703 cmꢁ1; EI-MS
m/z: 411 (Mþ), 271 (100%); Anal. Calcd for C22H29N5O3 (411.23):
C, 64.21; H, 7.10; N, 17.02. Found: C, 64.31; H, 7.01; N, 17.15.
leum ether: 1/3). 1H NMR (400 MHz, CDCl3)
d
¼7.93 (s, 1H, CH), 7.79
(d, J¼7.2 Hz, 2H, ArH), 7.69 (s, 1H, NH), 7.46e7.33 (m, 5H, ArH), 7.30
(d, J¼8 Hz, 2H, ArH), 6.12 (d, J¼14 Hz, 1H, CH2), 5.54 (s, 1H, CH), 5.48
(d, J¼14 Hz, 1H, CH2), 4.10e4.00 (m, 2H, CH2), 2.36 (s, 3H, CH3), 1.17
(t, J¼7.6 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3)
d¼164.53, 152.04,
4.2.12. Ethyl
6-methyl-2-oxo-3-[(4-pentyl-1H-1,2,3-triazol-1-yl)
148.68, 144.79, 139.61, 131.91, 130.09, 129.37, 128.85, 128.37, 125.76,
122.59,120.10,102.43, 60.43, 59.74, 57.60,18.61,14.08; IR (KBr): 3220,
3118, 2974, 1701, 1683, 1653, 1458, 1260, 1082, 764 cmꢁ1; EI-MS m/z:
497 (Mþþ2), 495 (Mþ), 350 (100%); Anal. Calcd for C23H22BrN5O3
(495.09): C, 55.65; H, 4.47; N,14.11. Found: C, 55.76; H, 4.36; N,14.26.
methyl]-4-p-tolyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate
(4l). White solid, mp 142e144 ꢀC; yield: 70% (ethyl acetate/petro-
leum ether: 1/4); 1H NMR (400 MHz, CDCl3)
d¼8.09 (s, 1H, NH), 7.44
(s, 1H, CH), 7.29 (d, J¼8 Hz, 2H, ArH), 7.12 (d, J¼7.6 Hz, 2H, ArH), 6.02
(d, J¼14 Hz, 1H, CH2), 5.47 (s, 1H, CH), 5.41 (d, J¼14.4 Hz, 1H, CH2),
4.08e3.99 (m, 2H, CH2), 2.66 (t, J¼8.8 Hz, 2H, CH2), 2.35 (s, 3H, CH3),
2.33 (s, 3H, CH3), 1.65e1.61 (m, 2H, CH2), 1.37e1.31 (m, 4H,
eCH2CH2e), 1.16 (t, J¼7.6 Hz, 3H, CH3), 0.90 (t, J¼7.2 Hz, 3H, CH3);
4.2.8. Ethyl 6-methyl-2-oxo-4-(4-flourophenyl)-3-[(4-phenyl-1H-1,2,
3-triazol-1-yl)-methyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate
(4h). White solid, mp 206e209 ꢀC; yield: 72% (ethyl acetate/pe-
13C NMR (100 MHz, CDCl3)
d
¼164.85, 152.74, 149.18, 145.05, 140.73,
troleum ether: 1/3). 1H NMR (400 MHz, CDCl3)
d
¼7.95 (s, 1H, CH),
128.68,128.41, 127.66, 121.01,102.57, 60.18, 60.14, 57.40, 31.42, 28.93,
25.56, 22.36, 18.30, 14.00, 13.95; IR (KBr): 3234, 3114, 2954, 1713,
1686, 1641, 1554, 1470, 1236, 1088, 792, 709 cmꢁ1; EI-MS m/z: 425
(Mþ), 285 (100%); Anal. Calcd for C23H31N5O3 (425.24): C, 64.92; H,
7.34; N, 16.46. Found: C, 65.03; H, 7.25; N, 16.59.
7.79 (d, J¼8 Hz, 2H, ArH), 7.61 (s, 1H, NH), 7.44e7.32 (m, 5H, ArH),
7.01 (t, J¼8.8 Hz, 2H, ArH), 6.13 (d, J¼14 Hz, 1H, CH2), 5.56 (s, 1H,
CH), 5.48 (d, J¼14 Hz, 1H, CH2), 4.12e3.97 (m, 2H, CH2), 2.37 (s, 3H,
CH3), 1.15 (t, J¼7.2 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3)
d
¼164.60, 152.06, 148.56, 144.55, 136.46, 130.13, 129.55, 129.47,
128.84, 128.35, 125.72, 120.11, 115.80, 115.59, 102.72, 60.35, 59.60,
57.51, 18.57, 14.05; IR (KBr): 3235, 3114, 2964, 1702, 1680, 1643,
1465, 1241, 1113, 772 cmꢁ1; EI-MS m/z: 435 (Mþ), 289 (100%); Anal.
4.2.13. Ethyl
6-methyl-2-oxo-4-p-tolyl-3-[(4-(4-(nitrophenoxy)
methyl)-1H-1,2,3-triazol-1-yl)methyl]-1,2,3,4-tetrahydropyrimidine-
5-carboxylate (4m). White solid; mp 194e196 ꢀC; yield: 73% (ethyl

886
Z.-J. Quan et al. / Tetrahedron 69 (2013) 881e887
acetate/petroleum ether: 1/3); 1H NMR (400 MHz, CDCl3)
d¼8.21
1H, CH2), 5.60 (s, 1H, CH), 5.50 (d, J¼12.8 Hz, 1H, CH2), 5.26 (s, 2H,
CH2), 2.42e2.26 (m, 2H, CH2), 2.22e2.11 (m, 2H, CH2), 1.09 (s, 3H,
(d, J¼9.2 Hz, 2H, ArH), 7.87 (s, 1H, CH), 7.58 (s, 1H, NH), 7.28
(d, J¼7.6 Hz, 2H, ArH), 7.13 (d, J¼8 Hz, 2H, ArH), 7.08 (d, J¼7.6 Hz, 2H,
ArH), 6.07 (d, J¼13.6 Hz,1H, CH2), 5.50 (s,1H, CH), 5.46 (d, J¼13.6Hz,
1H, CH2), 5.26 (s, 2H, CH2), 4.09e4.00 (m, 2H, CH2), 2.34 (s, 3H,
CH3), 2.32 (s, 3H, CH3), 1.17 (t, J¼7.6 Hz, 3H, CH3); 13C NMR
CH3), 0.95 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3)
d¼193.18,163.00,
152.31, 148.09, 142.18, 139.89, 128.88, 128.52, 127.24, 125.92, 114.78,
110.13, 109.88, 62.03, 58.64, 58.21, 50.07, 40.10, 32.79, 29.25, 27.18;
IR (KBr): 3232, 3112, 2960, 1679, 1677, 1636, 1595, 1497, 1443, 1377,
1248, 1110, 784 cmꢁ1; EI-MS m/z: 502 (Mþ), 281 (100%); Anal. Calcd
for C26H26N6O5 (502.20): C, 62.14; H, 5.21; N,16.72. Found: C, 62.23;
H, 5.11; N, 16.79.
(100 MHz, CDCl3)
d
¼164.78, 163.06, 152.30, 144.27, 143.32, 138.46,
137.54, 129.47, 127.54, 125.95, 123.86, 114.79, 102.94, 62.29, 60.33,
60.26, 57.80, 21.15, 18.53, 14.06; IR (KBr): 3230, 3112, 2980, 1716,
1688, 1641, 1472, 1224, 1085, 792 cmꢁ1; EI-MS m/z: 506 (Mþ), 271
(100%); Anal. Calcd for C25H26N6O6 (506.19): C, 59.28; H, 5.17; N,
16.59. Found: C, 59.36; H, 5.07; N, 16.71.
4.2.18. 7,7-Dimethyl-3-((4-((4-nitrophenoxy)methyl)-1H-1,2,3-
triazol-1-yl)methyl)-4-p-tolyl-3,4,7,8-tetrahydroquinazoline-
2,5(1H,6H)-dione (6c). White solid, mp 220e222 ꢀC; yield: 71%
(ethyl acetate/petroleum ether: 1/2); 1H NMR (400 MHz, CDCl3)
4.2.14. Ethyl 6-methyl-2-oxo-4-(4-methoxylphenyl)-3-[(4-(4-(nitroph-
enoxy)methyl)-1H-1,2,3-triazol-1-yl)methyl]-1,2,3,4-tetrahydropyrimi-
dine-5-carboxylate (4n). White solid, mp 180e182 ꢀC; yield: 71%
(ethyl acetate/petroleum ether: 1/2); 1H NMR (400 MHz, CDCl3)
d
¼8.21 (d, J¼9.2 Hz, 2H, ArH), 7.85 (s, 1H, CH), 7.75 (s, 1H, NH), 7.30
(d, J¼8 Hz, 2H, ArH), 7.13 (d, J¼8 Hz, 2H, ArH), 7.07 (d, J¼9.2 Hz, 2H,
ArH), 6.13 (d, J¼14.0 Hz, 1H, CH2), 5.53 (s, 1H, CH), 5.43
(d, J¼14.0 Hz, 1H, CH2), 5.26 (s, 2H, CH2), 2.40e2.23 (m, 2H, CH2),
2.31 (s, 3H, CH3), 2.21e2.10 (m, 2H, CH2), 1.08 (s, 3H, CH3), 0.96 (s,
d
¼8.21 (d, J¼9.2 Hz, 2H, ArH), 7.87 (s, 1H, CH), 7.87 (s, 1H, NH), 7.32
(d, J¼8.8 Hz, 2H, ArH), 7.08 (d, J¼7.4 Hz, 2H, ArH), 6.83 (d, J¼8.8 Hz,
2H, ArH), 6.06 (d, J¼14 Hz, 1H, CH2), 5.49 (d, J¼13.6 Hz, 1H, CH2), 5.48
(s,1H, CH), 5.26 (s, 2H, CH2), 4.10e4.01 (m, 2H, CH2), 3.79 (s, 3H, CH3),
2.35 (s, 3H, CH3), 1.17 (t, J¼7.6 Hz, 3H, CH3); 13C NMR (100 MHz,
3H, CH3). 13C NMR (100 MHz, CDCl3)
d
¼193.19, 163.02, 147.82,
143.21, 138.42, 136.92, 129.59, 127.28, 125.94, 123.82, 114.78, 110.20,
109.73, 62.31, 58.33, 57.88, 50.09, 40.15, 32.80, 29.27, 27.22, 21.16; IR
(KBr): 3231, 3102, 2951, 1682, 1675, 1647, 1589, 1481, 1439, 1341,
1253, 1097, 792 cmꢁ1; EI-MS m/z: 516 (Mþ), 295 (100%); Anal. Calcd
for C26H26N6O5 (516.21): C, 62.78; H, 5.46; N, 16.27. Found: C, 62.85;
H, 5.39; N, 16.31.
CDCl3)
d¼164.81, 1163.04, 159.66, 152.37, 144.18, 143.33, 141.88,
132.61, 128.88, 125.93, 123.82, 114.78, 114.08, 102.99, 62.26, 60.31,
60.01, 57.77, 55.27, 18.46, 14.08; IR (KBr): 3228, 3112, 2963, 1709,
1689, 1645, 1465, 1238, 1113, 1082, 796 cmꢁ1; EI-MS m/z: 522 (Mþ),
301 (100%); Anal. Calcd for C25H26N6O7 (522.19): C, 57.47; H, 5.02; N,
16.08. Found: C, 57.59; H, 4.92; N, 16.17.
4.2.19. N-Methyl-N-((4-phenyl-1H-1,2,3-triazol-1-yl)methyl)benza-
mide (8a). White solid, mp 121e123 ꢀC; yield: 78% (ethyl acetate/
4.2.15. Ethyl 6-methyl-3-[(4-(4-formylphenoxy)methyl)-1H-1,2,3-
triazol-1-yl]methyl]-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-
carboxylate (4o). White solid, mp 165e167 ꢀC; yield: 69% (ethyl
petroleum ether: 1/3); 1H NMR (400 MHz, CDCl3)
d
¼8.25 (s, 1H,
CH), 7.88 (d, J¼8 Hz, 2H, ArH), 7.47e7.34 (m, 8H, ArH), 6.02 (s, 2H,
CH2), 3.15 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3)
d¼148.41, 134.04,
acetate/petroleum ether: 1/2); 1H NMR (400 MHz, CDCl3)
d¼9.90 (s,
130.78, 130.22, 128.85, 128.32, 127.39, 125.97, 125.76, 120.80, 60.37,
37.11; IR (KBr): 3055, 2962, 1641, 1620, 1552, 1477, 1460, 1392, 1236,
1068, 874 cmꢁ1; EI-MS m/z: 292 (Mþ), 105 (100%); Anal. Calcd for
1H, CHO), 7.86 (s, 1H, CH), 7.85 (d, J¼7.2 Hz, 2H, ArH), 7.54 (s, 1H,
NH), 7.40e7.28 (m, 5H, ArH), 7.10 (d, J¼8.8 Hz, 2H, ArH), 6.06
(d, J¼14 Hz, 1H, CH2), 5.54 (s, 1H, CH), 5.49 (d, J¼14 Hz, 1H, CH2),
5.27 (s, 2H, CH2), 4.10e4.01 (m, 2H, CH2), 2.35 (s, 3H, CH3), 1.16
C17H16N4O (292.13): C, 69.85; H, 5.52; N, 19.17. Found: C, 69.96; H,
5.42; N, 19.26.
(t, J¼7.2 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3)
¼190.76, 164.70,
d
163.06, 152.24, 144.50, 143.77, 140.51, 132.00, 130.34, 128.77, 128.55,
127.59, 123.68, 115.01, 102.82, 61.95, 60.55, 60.33, 57.89, 18.55,
14.05; IR (KBr): 3230, 3109, 2850, 1689, 1643, 1556, 1461, 1244, 1157,
875, cmꢁ1; EI-MS m/z: 475 (Mþ), 271 (100%); Anal. Calcd for
C25H25N5O5 (475.19): C, 63.15; H, 5.30; N, 14.73. Found: C, 63.29;
H, 5.21; N, 14.82.
4.2.20. 4-Chloro-N-methyl-N-((4-phenyl-1H-1,2,3-triazol-1-yl)
methyl)benzamide (8b). White solid, mp 152e154 ꢀC; yield: 69%
(ethyl acetate/petroleum ether: 1/3); 1H NMR (400 MHz, CDCl3)
8.22 (s, 1H, CH), 7.78 (d, J¼7.6 Hz, 2H, ArH), 7.46e7.26 (m, 7H, ArH),
5.99 (s, 2H, CH2), 3.14 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3)
d
¼171.54, 148.38, 136.99, 132.36, 130.13, 128.95, 128.83, 128.33,
125.71, 120.78, 60.30, 37.10; IR (KBr): 3051, 2968, 1649, 1604, 1552,
1458, 1375, 1227, 1074, 768 cmꢁ1; EI-MS m/z: 328 (Mþþ2), 326
(Mþ), 139 (100%); Anal. Calcd for C17H15N4O (326.09): C, 62.48; H,
4.63; N, 17.15. Found: C, 62.52; H, 4.55; N, 17.23.
4.2.16. 7,7-Dimethyl-4-phenyl-3-((4-phenyl-1H-1,2,3-triazol-1-yl)
methyl)-3,4,7,8-tetrahydroquinazoline-2,5(1H,6H)-dione
(6a). White solid, mp 172e174 ꢀC; yield: 73% (ethyl acetate/pe-
troleum ether: 1/2); 1H NMR (400 MHz, CDCl3)
d
¼8.32 (br s, 1H,
NH), 7.96 (s, 1H, CH), 7.80 (d, J¼7.2 Hz, 2H, ArH), 7.46e7.31 (m, 8H,
ArH), 6.18 (d, J¼14 Hz, 1H, CH2), 5.64 (s, 1H, CH), 5.50 (d, J¼14 Hz,
1H, CH2), 2.43e2.27 (m, 2H, CH2), 2.22e2.11 (m, 2H, CH2), 1.09
4.2.21. N-Methyl-2-phenyl-N-((4-phenyl-1H-1,2,3-triazol-1-yl)
methyl)acetamide (8c). White solid, mp 98e100 ꢀC; yield: 73% (ethyl
acetate/petroleum ether: 1/3); 1H NMR (400 MHz, CDCl3)
d¼8.06
(s, 3H, CH3), 0.96 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3)
d¼193.13,
(s,1H, CH), 7.83 (d, J¼7.6 Hz, 2H, ArH), 7.46e7.27 (m, 6H, ArH), 7.20 (d,
152.56, 148.11, 140.06, 130.27, 128.91, 128.82, 128.53, 128.31, 127.41,
125.77, 120.26, 110.15, 58.59, 57.97, 50.11, 40.12, 32.78, 29.34, 27.17;
IR (KBr): 3226, 3118, 2955, 2887, 1689, 1668, 1641, 1554, 1450, 1337,
1259, 1089, 769 cmꢁ1; EI-MS m/z: 427 (Mþ), 281 (100%); Anal. Calcd
for C25H25N5O2 (427.20): C, 70.24; H, 5.89; N,16.38. Found: C, 70.31;
H, 5.76; N, 16.72.
J¼7.2Hz, 2H,ArH), 5.88 (s, 2H, CH2), 3.74 (s, 2H, CH2), 3.19 (s, 3H, CH3);
13C NMR (100 MHz, CDCl3)
d
¼172.54, 148.30, 133.54, 130.26, 129.38,
128.84, 128.80, 128.24, 127.21, 125.70, 120.55, 60.57, 40.71, 35.56; IR
(KBr):3061, 2967,1646,1629,1478,1398,1236,1072, 874 cmꢁ1; EI-MS
m/z: 306 (Mþ), 119 (100%); Anal. Calcd for C18H18N4O (306.15):
C, 70.57; H, 5.92; N, 18.29. Found: C, 70.69; H, 5.81; N, 18.36.
4.2.17. 7,7-Dimethyl-3-((4-((4-nitrophenoxy)methyl)-1H-1,2,3-
triazol-1-yl)methyl)-4-phenyl-3,4,7,8-tetrahydroquinazoline-
2,5(1H,6H)-dione (6b). White solid, mp 196e199 ꢀC; yield: 70%
(ethyl acetate/petroleum ether: 1/2); 1H NMR (400 MHz, CDCl3)
4.2.22. N-Methyl-2-phenoxy-N-((4-phenyl-1H-1,2,3-triazol-1-yl)
methyl)acetamide (8d). White solid, mp 125e127 ꢀC; yield: 72%
(ethyl acetate/petroleum ether: 1/3); 1H NMR (400 MHz, CDCl3)
d
¼8.00 (s, 1H, CH), 7.81 (d, J¼8.8 Hz, 2H, ArH), 7.45e7.26 (m, 5H,
d¼8.21 (d, J¼8.4 Hz, 2H, ArH), 8.03 (s, 1H, CH), 7.91 (s, 1H, NH),
ArH), 6.99 (t, J¼7.4 Hz, 1H, ArH), 6.92 (d, J¼8 Hz, 2H, ArH), 5.87
7.41e7.29 (m, 5H, ArH), 7.07 (d, J¼8 Hz, 2H, ArH), 6.15 (d, J¼13.2 Hz,
(s, 2H, CH2), 4.73 (s, 2H, CH2), 3.24 (s, 3H, CH3); 13C NMR (100 MHz,

Z.-J. Quan et al. / Tetrahedron 69 (2013) 881e887
887
6. (a) Li, H. M.; Cheng, F. O.; Duft, A. M.; Adronov, A. J. Am. Chem. Soc. 2005, 127,
14518e14524; (b) Rozkiewicz, D. I.; Janczewski, D.; Verboom, W.; Ravoo, B. J.;
Reinhoudt, D. N. Angew. Chem., Int. Ed. 2006, 45, 5292e5296; (c) Wyszogrodzka,
M.; Haag, R. Chem.dEur. J. 2008, 14, 9202e9214; (d) Gadzikwa, T.; Farha, O. K.;
Malliakas, C. D.; Kanatzidis, M. G.; Hupp, J. T.; Nguyen, S. T. J. Am. Chem. Soc.
2009, 131, 13613e13615; (e) Golas, P. L.; Matyjaszewski, K. Chem. Soc. Rev. 2010,
39, 1338e1354.
CDCl3)
d
¼169.47, 157.39, 148.40, 130.09, 129.64, 128.79, 128.29,
125.69, 121.97, 120.44, 114.53, 66.65, 60.45, 34.41; IR (KBr): 3056,
2964, 1641, 1591, 1461, 1323, 1234, 1068, 871 cmꢁ1; EI-MS m/z: 322
(Mþ), 107 (100%); Anal. Calcd for C18H18N4O2 (322.14): C, 67.07; H,
5.63; N, 17.38. Found: C, 67.19; H, 5.53; N, 17.49.
7. (a) Hahn, M. E.; Muir, T. W. Trends Biochem. Sci. 2005, 30, 26e34; (b) Heal, W. P.;
Wickramasinghe, S. R.; Leatherbarrow, R. J.; Tate, E. W. Org. Biomol. Chem. 2008,
6, 2308e2315; (c) Ahsanullah; Schmieder, P.; Kuhne, R.; Rademann, J. Angew.
Chem., Int. Ed. 2009, 48, 5042e5045; (d) Schneider, G. Nat. Rev. Drug Discovery.
2010, 9, 273e276.
8. (a) Chemama, M.; Fonvielle, M.; Arthur, M.; Valery, J. M.; Etheve-Quelquejeu, M.
Chem.dEur. J. 2009, 15, 1929e1938; (b) Nahrwold, M.; Bogner, T.; Eissler, S.;
Verma, S.; Sewald, N. Org. Lett. 2010, 12, 1064e1067; (c) Michaels, H. A.;
Murphy, C. S.; Clark, R. J.; Davidson, M. W.; Zhu, L. Inorg. Chem. 2010, 49,
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1252e1261.
4.2.23. N-Methyl-N-((4-phenyl-1H-1,2,3-triazol-1-yl)methyl)cinna-
mamide (8e). White solid, mp 129e131 ꢀC; yield: 71% (ethyl ace-
tate/petroleum ether: 1/3); 1H NMR (400 MHz, CDCl3)
CH), 7.85 (d, J¼8 Hz, 2H, ArH), 7.80 (d, J¼15.4 Hz, 1H, CH), 7.58e7.51
(m, 2H, ArH), 7.47e7.27 (m, 6H, ArH), 6.84 (d, J¼15.4 Hz, 1H, CH),
5.99 (s, 2H, CH2), 3.33 (s, 3H, CH3), 13C NMR (100 MHz, CDCl3)
d
¼8.13 (s,1H,
d
¼167.57, 148.28, 145.23, 134.46, 130.30, 128.81, 128.10, 125.69,
120.59, 115.62, 60.75, 35.13; IR (KBr): 3024, 2920, 1677, 1639, 1600,
1498, 1446, 1253, 1068, 875 cmꢁ1; EI-MS m/z: 318 (Mþ), 107 (100%);
Anal. Calcd for C19H18N4O (318.15): C, 71.68; H, 5.70; N, 17.60.
Found: C, 71.79; H, 5.61; N, 17.49.
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We are thankful for the financial support from the National
Nature Science Foundation of China (Nos. 20902073 and 21062017),
the Natural Science Foundation of Gansu Province (No.
096RJZA116), and the Scientific and Technological Innovation En-
gineering program of Northwest Normal University (Nos. nwnu-
kjcxgc-03-64, nwnulkqn-10-15).
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Supplementary data
These data include the copies of the NMR of the compounds
described in this article. Supplementary data related to this article
can be found online at http://dx.doi.org/10.1016/j.tet.2012.10.097.
References and notes
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14. Crystal data for 4d: formula: C23H22N6H5; unit cell parameters: a¼29.117 (17),
b¼12.967 (8), c¼12.067 (8);
a
¼90,
b
¼90, ¼90. These data can be obtained free
g
of charge. CCDC 856182 (4d) contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from the Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.