Facile and quantitative synthesis of 1,3-diazaheterocycle-fused 1,2,3-triazole derivatives using fluoroalkanesulfonyl azide as a diazo transfer reagent

Article abstract of DOI:10.1055/s-0030-1260043

A series of 1,3-diazaheterocycle-fused 1,2,3-triazoles were conveniently and quantitatively prepared by 1,3-dipolar cycloaddition of heterocyclic ketene aminals with fluoroalkanesulfonyl azide, followed by elimination of fluoroalkanesulfonyl amide at room

Full text of DOI:10.1055/s-0030-1260043

PAPER
1717
Facile and Quantitative Synthesis of 1,3-Diazaheterocycle-Fused 1,2,3-
Triazole Derivatives Using Fluoroalkanesulfonyl Azide as a Diazo Transfer
Reagent
1
,3-Diazah
i
eteroc
w
eriazoles i Gu, Wanting Xiong, Zhenhua Zhang, Shizheng Zhu*
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
345 Lingling Road, Shanghai 200032, P. R. of China
Fax +86(21)64166128; E-mail: zhusz@sioc.ac.cn
Received 28 February 2011; revised 31 March 2011
for example, 4-nitrophenyl azide gave exclusively 1,4,5-
Abstract: A series of 1,3-diazaheterocycle-fused 1,2,3-triazoles
were conveniently and quantitatively prepared by 1,3-dipolar cy-
cloaddition of heterocyclic ketene aminals with fluoroalkanesulfo-
nyl azide, followed by elimination of fluoroalkanesulfonyl amide at
room temperature without any catalyst.
trisubstituted 1,2,3-triazoles while 4-methoxyphenyl
azide afforded two products A (n = 2, 13% yield; n = 3,
31% yield) and B (n = 2, 18% yield; n = 3, 21% yield).
Recently Lin et al.1b reported an efficient one-pot three-
component method to prepare these compounds in about
90% yield (Scheme 2).
Key words: fluoroalkanesulfonyl azide, ketene aminals, 1,3-dipo-
lar cycloaddition, heterocycles, 1,3-diazaheterocycle-fused 1,2,3-
triazole
In continuation of our investigation on the fluoroalkane-
sulfonyl azides (RfSO2N3),5 we found that they react
readily with heterocyclic ketene aminals at room temper-
ature affording dipolar [3+2] cycloaddition products.
These eliminate fluoroalkanesulfonyl amide (RfSO2NH2)
to form the title products in quantitative yields. Due to the
higher polarity of the by-product RfSO2NH2, the product
was easily isolated from the reaction mixture. Herein we
wish to report these results.
In recent years, considerable attention has been devoted to
the development of new efficient methodology for the
preparation of heterocycle-fused 1,2,3-triazole deriva-
tives.1 These fused N-heterocyclic compounds possess
substantial biological activities including antitumor,2 anti-
microbial,3 and antifungal.4 Many methods for the synthe-
sis of 1,2,3-triazole derivatives have been reported. For
example, Huang and Wang1a first reported the diazahet-
erocycle-fused 1,2,3-triazole compounds, which were ob-
tained as a by-product from 1,3-dipolar cycloaddition of
aryl azides with benzoyl-substituted heterocyclic ketene
aminals (Scheme 1).
Fluoroalkanesulfonyl azides 1 (RfSO2N3) were prepared
from the reaction of the corresponding fluoroalkanesulfo-
nyl fluoride RfSO2F with NaN3 at room temperature in
MeCN.5a Fluoroalkanesulfonyl fluoride (RfSO2F) is much
cheaper than tetrafluoroisophalonitrile used in Lin’s pro-
tocol. The cyclic 1,1-enediamines such as 2-[(substituted-
benzoyl)methylene]hexahydropyrimidines 2 and 2-[(sub-
stituted-benzoyl)methylene]imidazolidines 3 were syn-
They found that the ratio of the two products depended on
the structure of the substitutuent group of the aryl azide,
O
H
Ph
H
N
H
N
N
Ph
+
COPh
(CH2)n
N3
R
(CH2)n
N
R
+
(CH2)n
N
H
H
N
N
N
N
N
N
A
B
n = 2, 3
89–13%
0–21%
Scheme 1 Reaction between cyclic 1,1-enediamines and aryl azides
F
F
O
H
N
O
H
N
NC
CN
NC
F
CN
F
R
DMF, r.t.
10 h
COR
NaN3
+
+
+
F
N
n
n
N
H
H
NH2
N
N
F
F
R = Me, 4-ClC6H4
4-MeC6H4
89–92% yield
86–90% yield
4-MeOC6H4
n = 1, 2
Scheme 2 Synthesis of heterocycle-fused 1,2,3-trizaole derivatives
SYNTHESIS 2011, No. 11, pp 1717–1722
x
x.
x
x
.
2
0
1
1
Advanced online publication: 13.05.2011
DOI: 10.1055/s-0030-1260043; Art ID: H23511SS
© Georg Thieme Verlag Stuttgart · New York

1718
J. Gu et al.
PAPER
thesized from the cyclocondensation of 1,3- gave the same good yield as the reaction conducted at
diaminopropane or ethylenediamine [NH2(CH2)nNH2 room temperature. Thus, in MeCN at room temperature,
(n = 2 or 3)] with a-oxoketene dithioacetals [Ar- the reaction of 1c (0.6 mmol) with 2a (0.5 mmol) was over
COCH=C(SMe)2] according to the literature method.6
in two hours (monitored by TLC and 19F NMR spectrum
analysis). Column chromatography using petroleum
ether–ethyl acetate (2:1) as eluent gave 4a in 99% yield.
According to the optimized reaction conditions (Table 1,
entry 8), a variety of heterocyclic ketene aminals were
treated with the fluoroalkanesulfonyl azides 1 to give the
product 4 or 5 in quantitative yield. It is worth mentioning
that heterocyclic ketene aminals with various substituents
and different ring sizes (n = 1, 0) were all good substrates
for this reaction (Table 2).
Initially, the reactions of azide I(CF2)2O(CF2)2SO2N3 (1c)
with the ketene 2a or 3a were chosen as models to test this
protocol under different conditions (Table 1).
As shown in Table 1, different solvents, such as THF, tol-
uene, and MeCN were used at different reaction tempera-
tures. It was found that MeCN was the best solvent to
afford the product 4a or 5a, and using a small excess of
azide at room temperature, the reaction gave the best yield
of the desired product. Higher reaction temperature
(70 °C) decreased the yield, while lower temperature
(0 °C) decreased the reaction rate. The reaction went to
completion within five to six hours at 0 °C in MeCN and
A proposed mechanism for this stepwise reaction is de-
picted in Scheme 3. The stepwise mechanism employed
in this case involves the initial formation of 7 from the re-
action of 2 or 3 with the fluoroalkanesulfonyl azide 1
Table 1 Reaction of 1c with 2a or 3a under Different Conditions
O
O
H
N
HN
RfSO2N3
+
RfSO2NH2
+
n
N
N
n
6c
H
HN
Rf = I(CF2)2O(CF2)2 1c
N
2a n = 1
3a n = 0
4a n = 1
5a n = 0
Entry
Solvent
2 or 3
2a
Mole ratioa
1:1
Temp (°C)
Time (h)
Product
4a
Yield (%)b
1
2
3
4
5
6
7
8
9
THF
0
r.t.
70
r.t.
r.t.
80
0
5
2
1
2
3
1
6
2
2
84
88
THF
2a
1:1
4a
THF
2a
1:1
4a
77
THF
2a
1.2:1
1.2:1
1.2:1
1.2:1
1.2:1
1.2:1
4a
94
toluene
toluene
MeCN
MeCN
MeCN
2a
4a
80
2a
4a
76
2a
4a
98
2a
r.t.
r.t.
4a
99
3a
5a
~100
a Mole ratio of azide 1 to ketene 2 or 3.
b Isolated yield, calculated based on the amount of 2a or 3a.
R
RfO2S
O
N
N
R
O
H
N
RfSO2N3
N
N
N
O
HN
HN
1
H
N
N
n
MeCN, r.t.
NH
n
H
n
H
R
SO2Rf
NH
2 n = 1
3 n = 0
8
7
R
O
N
O
H
R
N
N
N
N
H
NHSO2Rf
NH
n
N
– RfSO2NH2
N
6
n
9
4 or 5
Scheme 3 A possible mechanism for the formation of 4 or 5
Synthesis 2011, No. 11, 1717–1722 © Thieme Stuttgart · New York

PAPER
1,3-Diazaheterocycle-Fused 1,2,3-Triazoles
1719
(RfSO2N3) via an intermolecular 1,3-dipolar cycloaddi- roalkanesulfonyl amide 6 (RfSO2NH2) and cycloconden-
tion. The nitrogen–nitrogen bond breaks to form the inter- sation to obtain the target product 4 or 5.
mediate of 8, and the nitrogen atom of intermediate 8
attacks the N≡N bond to form 9, followed by loss of fluo-
Table 2 Synthesis of Diazaheterocycle-Fused 1,2,3-Triazoles 4 and 5a
O
R
O
H
R
N
HN
HN
MeCN
r.t., 2 h
+
RfSO2N3
RfSO2NH2
+
n
n
N
N
6a–c
H
Rf = C4F9 (1a)
N
HC2F4OC2F4 (1b)
IC2F4OC2F4 (1c)
2a–g n = 1
3a–g n = 0
4a–g n = 1
5a–g n = 0
Entry
2 or 3
Azide
Product
Mp (°C)
Yield (%)
99
O
N
O
H
154–156
N
HN
1
2a
1a
4a
157.5–158.5c
N
HN
N
154–156
2
3
2a
2a
1b
1c
4a
4a
99
99
157.5–158.5c
154–156
157.5–158.5c
O
N
O
H
N
H
193–195
N
4
3a
1a
5a
99
199.5–201c
N
H
N
N
193–195
5
6
3a
3a
1b
1c
5a
5a
99
199.5–201c
193–195
100
199.5–201c
O
O
H
168–170
171–172c
N
MeO
HN
7
8
2b
2c
2d
2e
2f
1a
1a
1a
1a
1a
4b
4c
4d
4e
4f
99
96
98
99
96
MeO
N
N
HN
N
O
O
H
152–155
155–156c
N
HN
HN
N
N
N
O
O
H
N
O2N
HN
HN
9
223–225
170–172
170–172
O2N
N
N
N
O
O
H
N
Br
HN
HN
10
11
Br
N
N
N
O
O
H
N
F
HN
HN
F
N
N
N
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1720
J. Gu et al.
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Table 2 Synthesis of Diazaheterocycle-Fused 1,2,3-Triazoles 4 and 5a (continued)
O
R
O
H
R
N
HN
HN
MeCN
r.t., 2 h
+
RfSO2N3
RfSO2NH2
+
n
n
N
N
6a–c
H
Rf = C4F9 (1a)
N
HC2F4OC2F4 (1b)
IC2F4OC2F4 (1c)
2a–g n = 1
3a–g n = 0
4a–g n = 1
5a–g n = 0
Entry
2 or 3
Azide
Product
Mp (°C)
247–248
Yield (%)
89
Cl
O
F
F
Cl
O
H
12
2g
1a
4g
N
HN
HN
N
N
Cl
Cl
N
O
N
O
H
N
H
MeO
N
13
14
15
16
17
3b
3c
3d
3e
3f
1a
1a
1a
1a
1a
5b
5c
5d
5e
5f
207–209
~100
99
MeO
N
H
N
N
O
O
H
H
224–227
229–231c
N
N
N
H
N
N
N
O
O
H
N
H
O2N
N
249–251
214–216
222–224
94
O2N
N
H
N
N
N
O
O
H
H
Br
N
N
98
Br
N
N
H
N
N
O
O
H
H
F
F
N
N
98
F
F
N
H
N
N
N
N
N
Cl
Cl
Cl
O
N
O
H
H
18
3g
1a
5g
263–265
88
N
N
N
H
Cl
a Mole ratio of 1:2 or 3 is 1.2:1.
b Isolated yield, calculated based on the amount of 2 or 3.
c See reference 1a.
The reaction was also carried out in one pot using the three In summary, we have developed a convenient synthesis of
components, heterocyclic ketene aminals 3a, fluoroal- biologically significant diazaheterocycle-fused 1,2,3-tria-
kanesulfonyl fluoride (RFSO2F), and sodium azide in zole derivatives in quantitative yields at room temperature
MeCN at room temperature. However, even after using an without any catalyst. This method is applicable to various
excess of I(CF2)2O(CF2)2SO2F (1.2 equiv) and NaN3 (1.5 heterocyclic ketene aminals and fluoroalkanesulfonyl
equiv) under stirring for 48 hours, only about 68% of 2a azides and is suitable for combinatorial and parallel syn-
(1.0 equiv) was transformed to the product 4a, which was thesis in new drug discovery. Thus, a library of 1,3-diaza-
isolated in 54% yield (Scheme 4). Considering that the re- heterocycle-fused
1,2,3-triazole
derivatives
was
action of NaN3 with RfSO2F in MeCN was complete with- constructed in a facile manner by this protocol.
in 24 hours at room temperature, it was supposed that in
the one-pot reaction process the formed fluoroalkane-
sulfonyl amide (RfSO2NH2) delayed the formation of
RfSO2N3, due to its weaker acidity.
Unless otherwise indicated, chemicals and solvents were purchased
from commercial suppliers and purified by standard techniques. Pe-
troleum ether used refers to the fraction boiling in the range 60–90
Synthesis 2011, No. 11, 1717–1722 © Thieme Stuttgart · New York

PAPER
1,3-Diazaheterocycle-Fused 1,2,3-Triazoles
1721
O
H
N
O
MeCN
HN
HN
RfSO2F
+
NaN3
+
RfSO2NH2
+
r.t., 48 h
1c
N
H
N
Rf = I(CF2)2O(CF2)2
N
2a
4a 54%
Scheme 4 One-pot synthesis of 4a
°C. Flash column chromatography was performed using silica gel.
For TLC, compounds were visualized by irradiation with UV light.
For NMR spectroscopy, samples were dissolved in CDCl3 or
DMSO-d6 and recorded at r.t. The 1H NMR (300 MHz), 13C NMR
(100 MHz), and 19F NMR (282 MHz) spectra were recorded on a
Bruker AM-300 UltraShield, 300 MHz, 400 MHz, high-perfor-
mance digital FT-NMR spectrometer with TMS as the internal stan-
dard. All chemical shifts (d) are given in ppm. Data are reported as
follows: chemical shift, number of hydrogens, multiplicity
(s = single, d = doublet, t = triplet, q = quartet, br = broad, and
m = multiplet) and coupling constants (Hz). Melting points were
determined on a Mel-Temp apparatus and are uncorrected. IR spec-
tra were obtained with a Nicolet AV 360 spectrophotometer. Low-
resolution mass spectra (LRMS) and high-resolution mass spectra
(HRMS) were obtained on Finnigan GC-MS 4021 and MAT-8430
instruments using the electron-impact ionization technique (70 eV)
or electrospray ionization. Elemental analyses were performed by
Shanghai Institute of Organic Chemistry.
CH2N), 3.89 (3 H, s, OCH3), 3.54–3.49 (2 H, m, CH2N), 2.20 (2 H,
quint, J = 6.0 Hz, CH2).
3-(4¢-Methylbenzoyl)-4,5,6,7-tetrahydro[1,2,3]triazolo[1,5-
a]pyrimidine (4c)
Yield: 116 mg (96%); white solid; mp 152–155 °C (Lit.1a mp 155–
156 °C).
1H NMR (300 MHz, CDCl3): d = 8.40 (2 H, d, J = 8.4 Hz), 7.30 (2
H, d, J = 8.4 Hz), 6.70 (1 H, br s, NH), 4.37 (2 H, t, J = 6.0 Hz,
CH2N), 3.52 (2 H, t, J = 6.0 Hz, CH2N), 2.42 (3 H, s, ArCH3), 2.20
(2 H, quint, J = 6.0 Hz, CH2).
3-(4¢-Nitrobenzoyl)-4,5,6,7-tetrahydro[1,2,3]triazolo[1,5-a]py-
rimidine (4d)
Yield: 134 mg (98%); pale yellow solid; mp 223–225 °C.
IR (KBr): 3399, 1637, 1576, 1519, 1342, 1200 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.64 (2 H, d, J = 8.7 Hz), 8.33 (2
H, d, J = 8.7 Hz), 6.72 (1 H, br s, NH), 4.41 (2 H, t, J = 6.0 Hz,
CH2N), 3.58 (2 H, br s, CH2N), 2.25 (2 H, t, J = 5.1 Hz, CH2).
13C NMR (75 MHz, DMSO-d6): d = 181.3, 149.1, 145.8, 142.4,
130.6, 127.5, 123.3, 42.8, 38.2, 19.5.
Heterocycle-Fused 1,2,3-Triazole Derivatives; 3-(4¢-Bromoben-
zoyl)-4,5,6,7-tetrahydro[1,2,3]triazolo[1,5-a]pyrimidine (4e);
Typical Procedure
To a solution of 2e (140 mg, 0.5 mmol) in MeCN (10 mL) was add-
ed nonafluorobutanesulfonyl azide (1a; 270 mg, 0.6 mmol) and the
mixture stirred at r.t. for 2 h. The reaction was monitored by TLC.
After completion of the reaction, the resulting mixture was concen-
trated under reduced pressure, and the residue was then purified by
flash chromatography (petroleum ether–EtOAc, 2:1) to provide 4e
as a pale yellow solid product; yield: 148 mg (99%); mp 170–
172 °C.
MS (EI): m/z = 273 (M+, 22), 244 (59), 205 (18), 91 (49), 43 (100).
HRMS (EI): m/z calcd for C12H11N5O3: 273.0862; found: 273.0866.
3-(4¢-Fluorobenzoyl)-4,5,6,7-tetrahydro[1,2,3]triazolo[1,5-
a]pyrimidine (4f)
Yield: 118 mg (96%); white solid; mp 170–172 °C (Lit.1f mp 163–
164 °C).
IR (KBr): 3324, 2973, 1665, 1423, 1341, 1139, 1067 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.59–8.54 (2 H, m), 7.17 (2 H, t,
J = 9.0 Hz), 6.70 (1 H, br s, NH), 4.39 (2 H, t, J = 6.0 Hz, CH2N),
3.56–3.51 (2 H, m, CH2N), 2.22 (2 H, quint, J = 6.0 Hz, CH2).
19F NMR (282 MHz, CDCl3): d = –109.0 (m, ArF).
1H NMR (300 MHz, CDCl3): d = 8.39 (2 H, d, J = 8.7 Hz), 7.63 (2
H, d, J = 8.7 Hz), 6.68 (1 H, br s, NH), 4.38 (2 H, t, J = 5.7 Hz,
CH2N), 3.53 (2 H, t, J = 5.7 Hz, CH2N), 2.22 (2 H, quint, J = 5.7 Hz,
CH2).
13C NMR (100 MHz, CDCl3): d = 183.9, 146.2, 136.0, 131.6, 131.4,
128.4, 127.3, 43.2, 38.8, 20.4.
3-(2¢,6¢-Dichloro-3¢-fluorobenzoyl)-4,5,6,7-tetrahydro[1,2,3]tri-
azolo[1,5-a]pyrimidine (4g)
Yield: 140 mg (89%); white solid; mp 247–248 °C.
IR (KBr): 3345, 1652, 1611, 1452, 1437, 1264, 1202 cm–1.
MS (ESI): m/z = 306.9 ([M + H]+).
Anal. Calcd for C12H11BrN4O: C, 46.93; H, 3.61; N, 18.24. Found:
C, 46.77; H, 3.53; N, 18.49.
1H NMR (300 MHz, CDCl3): d = 7.34 (1 H, q, J = 4.5 Hz), 7.17 (1
H, t, J = 8.4 Hz), 6.45 (1 H, br s, NH), 4.38 (2 H, t, J = 6.0 Hz,
CH2N), 3.60–3.55 (2 H, m, CH2N), 2.25 (quint, 2 H, J = 5.7 Hz,
CH2).
13C NMR (75 MHz, CDCl3): d = 183.4, 156.9 (d, J = 248.9 Hz),
145.1, 139.0, 129.0 (d, J = 7.3 Hz), 128.1, 126.6, 126.5, 117.6 (d,
J = 22.9 Hz), 43.1, 38.6, 20.3.
3-Benzoyl-4,5,6,7-tetrahydro[1,2,3]triazolo[1,5-a]pyrimidine
(4a)
Yield: 113 mg (99%); white solid; mp 154–156 °C (Lit.1a mp
157.5–158.5 °C).
1H NMR (300 MHz, CDCl3): d = 8.47 (2 H, dd, J = 1.8, 8.1 Hz),
7.56–7.47 (3 H, m), 6.73 (1 H, br s, NH), 4.37 (2 H, t, J = 6.0 Hz,
CH2N), 3.54–3.49 (2 H, m, CH2N), 2.20 (2 H, quint, J = 6.0 Hz,
CH2).
19F NMR (282 MHz, CDCl3): d = –116.3 (q, J = 3.9 Hz, ArF).
MS (EI): m/z = 318/316/314 (M+, 2/12/20), 279 (14), 251 (100), 223
(30), 191 (22), 41 (70).
3-(4¢-Methoxybenzoyl)-4,5,6,7-tetrahydro[1,2,3]triazolo[1,5-
HRMS (EI): m/z calcd for C12H9Cl2FN4O: 314.0137; found:
314.0136.
a]pyrimidine (4b)
Yield: 128 mg (99%); white solid; mp 168–170 °C (Lit.1a mp 171–
172 °C).
1H NMR (300 MHz, CDCl3): d = 8.56 (2 H, d, J = 9.0 Hz), 6.99 (2
H, d, J = 9.0 Hz), 6.70 (1 H, br s, NH), 4.38 (2 H, t, J = 6.0 Hz,
Anal. Calcd for C12H9Cl2FN4O: C, 45.74; H, 2.88; N, 17.78. Found:
C, 46.24; H, 3.11; N, 17.63.
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J. Gu et al.
PAPER
3-Benzoyl-5,6-dihydro-4H-imidazo[1,2-c][1,2,3]triazole (5a)
Yield: 107 mg (99%); white solid; mp 193–195 °C (Lit.1a mp
199.5–201 °C).
3-(2¢,6¢-Dichloro-3¢-fluorobenzoyl)-5,6-dihydro-4H-imida-
zo[1,2-c][1,2,3]triazole (5g)
Yield: 132 mg (88%); white solid; mp 263–265 °C.
1H NMR (300 MHz, CDCl3): d = 8.48–8.45 (2 H, m), 7.58–7.48 (3
H, m), 5.50 (1 H, br s, NH), 4.54–4.40 (4 H, m, 2 CH2N).
IR (KBr): 3360, 1652, 1605, 1452, 1432, 1301, 1272, 1188, 1010
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.34 (1 H, q, J = 4.5 Hz), 7.18 (1
H, t, J = 8.4 Hz), 5.36 (1 H, br s, NH), 4.52 (4 H, br s, 2 CH2N).
19F NMR (282 MHz, CDCl3): d = –116.3 (q, J = 3.9 Hz, ArF).
3-(4¢-Methoxybenzoyl)-5,6-dihydro-4H-imidazo[1,2-
c][1,2,3]triazole (5b)
Yield: 122 mg (~100%); white solid; mp 207–209 °C (Lit.1a mp
215–216 °C).
MS (EI): m/z = 304/302/300 (M+, 1/4/6), 237 (100), 209 (17), 189
1H NMR (300 MHz, CDCl3): d = 8.56 (2 H, d, J = 9.0 Hz), 6.99 (2
H, d, J = 9.0 Hz), 5.33 (1 H, br s, NH), 4.54–4.39 (4 H, m, 2 CH2N),
3.89 (3 H, s, OCH3).
(79), 163 (17), 111 (24).
Anal. Calcd for C11H7Cl2FN4O: C, 43.88; H, 2.34; N, 18.61. Found:
C, 44.19; H, 2.50; N, 18.31.
3-(4¢-Methylbenzoyl)-5,6-dihydro-4H-imidazo[1,2-c][1,2,3]tria-
zole (5c)
Acknowledgment
Yield: 113 mg (99%); pale yellow solid; mp 224–227 °C (Lit.1a mp
229–231 °C).
1H NMR (300 MHz, CDCl3): d = 8.40 (2 H, d, J = 7.2 Hz), 7.30 (2
H, d, J = 7.2 Hz), 5.37 (1 H, br s, NH), 4.48 (2 H, d, J = 6.8 Hz,
CH2N), 4.43 (2 H, d, J = 6.8 Hz, CH2N), 2.42 (3 H, s, ArCH3).
We gratefully acknowledge the financial support from National
Natural Science Foundation of China (No.21032006 and
No.20972178).
References
3-(4¢-Nitrobenzoyl)-5,6-dihydro-4H-imidazo[1,2-c][1,2,3]tria-
zole (5d)
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Yield: 122 mg (94%); yellow solid; mp 249–251 °C.
IR (KBr): 3197, 1639, 1581, 1519, 1430, 1349, 1295, 1172 cm–1.
1H NMR (300 MHz, DMSO-d6): d = 8.49 (2 H, d, J = 8.7 Hz), 8.39
(2 H, d, J = 8.7 Hz), 7.73 (1 H, br s, NH), 4.49 (2 H, t, J = 9.0 Hz,
CH2N), 4.29 (2 H, t, J = 9.0 Hz, CH2N).
13C NMR (75 MHz, DMSO-d6): d = 181.8, 156.0, 149.8, 142.4,
131.3, 125.5, 123.9, 53.1, 44.8.
MS (EI): m/z = 222 (57), 144 (7), 105 (100), 77 (57).
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Chem. 2008, 16, 4829.
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Barbachyn, M. R.; Emmert, D. E.; Garmon, S. A.; Graber, D.
R.; Grega, K. C.; Hester, J. B.; Hutchinson, D. K.; Morris, J.;
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HRMS (EI): m/z calcd for C11H9N5O3: 259.0705; found: 259.0709.
3-(4¢-Bromobenzoyl)-5,6-dihydro-4H-imidazo[1,2-c][1,2,3]tria-
zole (5e)
Yield: 143 mg (98%); pale yellow solid; mp 214–216 °C.
IR (KBr): 3380, 1783, 1643, 1159, 1104, 1069, 1010 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.38 (2 H, d, J = 8.7 Hz), 7.63 (2
H, d, J = 8.7 Hz), 5.38 (1 H, br s, NH), 4.48 (4 H, dd, J = 6.9, 14.1
Hz, 2 CH2N).
13C NMR (100 MHz, CDCl3): d = 183.5, 155.7, 135.3, 131.8, 131.6,
128.0, 126.8, 53.0, 44.8.
MS (EI): m/z = 294/292 (M+, 21/21), 265 (42), 236 (27), 183 (100),
157 (44), 102 (34).
Anal. Calcd for C11H9BrN4O: C, 45.07; H, 3.09; N, 19.11. Found:
C, 44.86; H, 3.19; N, 19.14.
3-(4¢-Fluorobenzoyl)-5,6-dihydro-4H-imidazo[1,2-c][1,2,3]tria-
zole (5f)
Yield: 114 mg (98%); pale yellow solid; mp 222–224 °C.
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Huang, Q.-C. J. Fluorine Chem. 2000, 106, 133. (d) Zhu,
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(6) (a) Huang, Z.-T.; Wamhoff, H. Chem. Ber. 1984, 117, 622.
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1527.
IR (KBr): 3344, 1628, 1600, 1428, 1230, 1154 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.60–8.55 (2 H, m), 7.18 (2 H, t,
J = 8.4 Hz), 5.30 (1 H, br s, NH), 4.49 (4 H, dd, J = 6.0, 14.7 Hz, 2
CH2N).
19F NMR (282 MHz, CDCl3): d = –106.2 (m, ArF).
MS (EI): m/z = 232 (M+, 9), 204 (22), 176 (17), 121 (100), 95 (43),
75 (20).
Anal. Calcd for C11H9FN4O: C, 56.89; H, 3.91; N, 24.13. Found: C,
57.28; H, 4.22; N, 23.74.
Synthesis 2011, No. 11, 1717–1722 © Thieme Stuttgart · New York