Synthesis of phenylazides and 1-phenyl-1,2,3-triazoles bearing (E)-2-halovinyl group

Article abstract of DOI:10.1007/s11172-010-0100-9

Treatment of (E)-3-(4-azidophenyl)and (E)-3-(2-azidophenyl)acrylic acid with N-halosuccinimides in the presence of LiOAc afforded high yields of phenylazides containing (E)-2-halovinyl group. The latter were transformed to different phenyl-1,2,3-triazoles

Full text of DOI:10.1007/s11172-010-0100-9

Russian Chemical Bulletin, International Edition, Vol. 59, No. 2, pp. 452—456, February, 2010
452
Synthesis of phenylazides and 1ꢀphenylꢀ1,2,3ꢀtriazoles
bearing (E)ꢀ2ꢀhalovinyl group
W. Zhang,a,b C. Su,a C. Kuang,a and Q. Yangc
aDepartment of Chemistry, Tongji University,
1239 Siping Road, 200092 Shanghai, China.
Fax: +86 (21) 659 83191. Eꢀmail: kuangcx@tongji.edu.cn
bDepartment of Chemistry, Jiaozuo Teachers College,
998 Shanyang Road, 450001 Jiaozuo Henan, China
cSchool of Pharmacy, Fudan University,
138 Yixueyuan Road, 200032 Shanghai, China.
Fax: +86 (21) 542 37692
Treatment of (E)ꢀ3ꢀ(4ꢀazidophenyl)ꢀ and (E)ꢀ3ꢀ(2ꢀazidophenyl)acrylic acid with Nꢀhaloꢀ
succinimides in the presence of LiOAc afforded high yields of phenylazides containing
(E)ꢀ2ꢀhalovinyl group. The latter were transformed to different phenylꢀ1,2,3ꢀtriazoles bearing
(E)ꢀhalovinyl group by the CuIꢀcatalyzed reaction of 1,3ꢀdipolar cycloaddition.
Key words: phenylazides, 1,2,3ꢀtriazoles, (E)ꢀvinyl halides, 1,3ꢀdipolar cycloaddition.
Scheme 1
Aromatic azides are versatile synthetic intermediates
in organic and biоorganic chemistry.1 Their use as reacꢀ
tants for the introduction of photoaffinic label of biоmoleꢀ
cules is especially important.2 1,2,3ꢀTriazoles are widely
used as pharmaceutical drugs and agrochemical materiꢀ
als.3 Discovery of a CuIꢀcatalyzed 1,3ꢀdipolar cycloaddiꢀ
tion of azides and terminal alkynes4 provided further use
of 1,2,3ꢀtriazoles for biоconjugation, search for medical
drugs,5 in material science,6 and combinatorial chemisꢀ
try7. In addition, a number of compounds containing
1,2,3ꢀtriazole fragment exhibited a wide range of biоlogiꢀ
cal activity: antibacterial,8 herbicide and fungicide,9 antiꢀ
allergic,10 and antiꢀHIV.11
At the same time, (E)ꢀvinyl halides are extremely useꢀ
ful building blocks in organic synthesis and serve as vinylꢀ
anion precursors12 and bridging components in the tranꢀ
sition metal catalyzed coupling reactions.13 This stimulꢀ
ates requirements in the easily available 1,2,3ꢀtriazoles
bearing (E)ꢀhalovinyl group, and, consequently, neccesꢀ
sity to develop reliable and efficient methods for the synꢀ
thesis of phenylazides containing (E)ꢀhalovinyl group.
In the present work, we describe a simple method deꢀ
veloped for the stereoselective synthesis of phenylazides 2
containing (E)ꢀhalovinyl group from easily available
(E)ꢀ3ꢀ(4ꢀazidophenyl)ꢀ and (E)ꢀ3ꢀ(2ꢀazidophenyl)acrylic
acids 1 (Scheme 1). Phenylꢀ1,2,3ꢀtriazoles 3 bearing
(E)ꢀhalovinyl group were synthesized by the CuIꢀcataꢀ
lyzed reaction of 1,3ꢀdipolar cycloaddition4 of the correꢀ
sponding azides 2 and terminal alkynes in high yields.
We started from the study of the reaction of acid 1a
with NBS. The reaction proceeds in a MeCN—H2O solꢀ
Reagents and conditions: i. LiOAc, MeCN—H2O (9 : 1, v/v),
~20 or 80 °C. ii. R—C≡CH, CuI, sodium ascorbate, DMSO, ~20 °C.
1: 4ꢀN3 (a), 2ꢀN3 (b);
2: 4ꢀN3, X = Br (a); 2ꢀN3, X = Br (b); 4ꢀN3, X = I (c);
4ꢀN3, X = C l (d)
3
R
X
3
R
X
a
b
c
d
e
f
EtO2C
HOH2C
nꢀC5H11
Ph
4ꢀBrC6H4
4ꢀ(PhNHSO2)C6H4 Br
Br
Br
Br
Br
Br
g
h
i
j
k
4ꢀ(PhN(Me)SO2)C6H4 Br
EtO2C
HOH2C
EtO2C
EtO2C
Br
Br
I
Cl
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 442—446, February, 2010.
1066ꢀ5285/10/5902ꢀ0452 © 2010 Springer Science+Business Media, Inc.

Phenylꢀ1,2,3ꢀtriazoles bearing (E)ꢀ2ꢀhalovinyl group Russ.Chem.Bull., Int.Ed., Vol. 59, No. 2, February, 2010
453
Table 2. Synthetic conditions and yields of phenylꢀ1,2,3ꢀtriꢀ
azoles 3a—k
vent mixture (9 : 1, v/v) with LiOAc as a catalyst to yield
phenylazide 2a in 96% yield (Table 1, entry 1). Though,
the MeCN—H2O solvent mixture (9 : 1, v/v) has proved
the most favorable reaction medium for the stereoconꢀ
trolled synthesis of (E)ꢀarylvinylhalides 2, a dropwise adꢀ
dition of a solution of NBS in MeCN to the reaction
mixture considerably increased efficiency of the reaction.
The reaction of acid 1b with NBS under the same condiꢀ
tions as for acid 1a also led to compound 2b in high yield
(see Table 1, entry 2). The reaction of compounds 1a,b
with NBS can be performed at room temperature for only
10 min after addition of NBS to obtain high yields of the
corresponding phenylazides 2a,b, in this case no irradiaꢀ
tion with microwaves is required as in the known proceꢀ
dure.14 However for the reaction of acid 1a with NIS
(NCS) yielding compounds 2c,d in satisfactory yields, elꢀ
evated temperature is required (80 °C, 1 h) (see Table 1,
entries 3 and 4).
Further, we considered a CuIꢀcatalyzed reaction of
1,3ꢀdipolar cycloaddition of phenylazides 2 and terminal
alkynes. (E)ꢀ1ꢀAzidoꢀ4ꢀ(2ꢀbromovinyl)benzene (2a) was
chosen as a model reactant in the reaction with ethyl proꢀ
piolate. The reaction proceeded for 12 h in DMSO at
room temperature under nitrogen to form triazole 3a in
95% yield (Table 2, entry 1).
Versatility and limitations of this method were thorꢀ
oughly studied using different alkynes as an example unꢀ
der the same conditions as for the reaction of phenylazide
2a with ethyl propiolate. Aliphatic alkynes (propꢀ2ꢀynꢀ1ꢀ
ol and heptꢀ1ꢀyne) gave triazoles 3b,c in 89 and 87% yields,
respectively (see Table 2, entries 2 and 3). Aromatic alkynes
(ethynylbenzene and 1ꢀbromoꢀ4ꢀethynylbenzene) yielded
products 3d,e in 88 and 85% yield, respectively (see Table 2,
entries 4 and 5). This method has proved very efficient
even for the sterically hindered aromatic alkynes, such as
Nꢀphenylꢀ4ꢀethynylbenzenesulfonamide and Nꢀmethylꢀ
Nꢀphenylꢀ4ꢀethynylbenzenesulfonamide, from which triꢀ
azoles 3f,g were obtained in 84 and 82% yields (see Table 2,
entries 6 and 7).
Entry Azide
R
Proꢀ
ducta,b
Yieldc
(%)
(in R—C≡CH)
1
2
3
4
5
6
7
8
2a
2a
2a
2a
2a
2a
2a
2b
2b
2c
2d
EtO2C
HOH2C
nꢀC5H11
3a
3b
3c
3d
3e
3f
3g
3h
3i
95
89
87
88
85
84
82
84
83
92
91
Ph
4ꢀBrC6H4
4ꢀ(PhNHSO2)C6H4
4ꢀ(PhN(Me)SO2)C6H4
EtO2C
9
10
11
HOH2C
EtO2C
EtO2C
3j
3k
a
Reaction conditions: 2 (1 mmol), R—C≡CH (1.05 mmol),
DMSO (5 mL), sodium ascorbate (0.15 mmol), CuI (0.15 mmol),
N2, ~20 °C, 12 h.
b E : Z > 99 : 1 (1H NMR data).
c Calculated on phenylazide 2.
We also studied behavior of (E)ꢀ1ꢀazidoꢀ2ꢀ(2ꢀbromoꢀ
vinyl)benzene (2b) in the reactions with ethyl propiolate
and propꢀ2ꢀynꢀ1ꢀol. The same conditions as for 2a proꢀ
duced compounds 3h,i in 84 and 83% yields, respectively
(see Table 2, entries 8 and 9).
As we expected, the reaction of ethyl propiolate with
compounds 2c,d led to triazoles 3j,k in good yields (see
Table 2, entries 10 and 11).
In conclusion, we developed simple method for the
synthesis of phenylazides containing (E)ꢀhalovinyl group
under mild conditions and in high yields by the reaction of
easily available (E)ꢀ3ꢀ(4ꢀazidophenyl)ꢀ and (E)ꢀ3ꢀ(2ꢀ
azidophenyl)acrylic acids with Nꢀhalosuccinimides (NBS,
NIS, and NCS). In addition, a series of phenylꢀ1,2,3ꢀ
triazoles bearing (E)ꢀhalovinyl group was synthesized by
the CuIꢀcatalyzed reaction of 1,3ꢀdipolar cycloaddition of
the corresponding azides and terminal alkynes.
Table 1. Synthetic conditions and yields of phenylazides 2a—d
Experimental
Entry
Subꢀ
strate
NꢀHalosucꢀ
cinimide
Synthetic Proꢀ
conditionsa ductb
Yieldc
(%)
Melting points were determined on a A. Krüss Optronic
GmbH KSPII apparatus and uncorrected. IR spectra were obꢀ
tained on a Nexus FTꢀIR spectrophotometer. 1H and 13C NMR
spectra were recorded on a Bruker AMꢀ300 and Bruker AMꢀ500
spectrometer using Me4Si as an internal standard. Elemental
analysis was performed on a Perkin—Elmer 2400 CHNS eleꢀ
mental analyzer. Commercially available reactants were used as
purchased. All the reactions were monitored by TLC on Huangꢀ
haiGF 254 plates with silica gel. Column chromatography
was performed on silica gel (300—400 mesh) under moderate
pressure.
1
2
3
4
1a
1b
1a
1a
NBS
NBS
NIS
A
A
B
B
2a
2b
2c
2d
96
93
90
91
NCS
a A: 1 (1.1 mmol), LiOAc (0.2 mmol), MeCN—H2O solvent
mixture (10 mL, 9 : 1, v/v), NBS (1 mmol) in MeCN (5 mL),
~20 °C, 10 min; B: 1 (1.1 mmol), LiOAc (0.2 mmol),
MeCN—H2O solvent mixture (10 mL, 9 : 1, v/v), NIS or NCS
(1 mmol) in MeCN (5 mL), 80 °C, 1 h.
Synthesis of (E)ꢀ3ꢀ(4ꢀazidophenyl)ꢀ and (E)ꢀ3ꢀ(2ꢀazidoꢀ
phenyl)acrylic acids 1a,b. Zinc powder (3.900 g, 60 mmol) was
added to a stirred suspension (100 mL) of 3ꢀ(4ꢀ or 2ꢀnitroꢀ
b E : Z > 99 : 1 (1H NMR data).
c Calculated on Nꢀhalosuccinimide.

454
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 2, February, 2010
Zhang et al.
phenyl)acrylic acid (5.790 g, 30 mmol) in AcOH—H2O (9 : 1,
v/v) obtained from 4ꢀ or 2ꢀnitrobenzaldehyde according to
a standard procedure.15 The reaction mixture was stirred for 0.5 h at
~20 °C and filtered. The filtrate was cooled to 0 °C in an ice
bath, followed by a dropwise addition of a solution of sodium
nitrite (2.484 g, 36 mmol) in water (20 mL). The mixture was
stirred for 10 min at 0 °C, sodium azide (2.340 g, 36 mmol) in
water (20 mL) was added dropwise to it. After the reaction was
completed, the solvent was evaporated. The combined organic
layers were washed with brine (2×100 mL) and cold water
(100 mL) and dried with anhydrous Na2SO4. Crude product was
obtained after evaporation of the solvent, which was recrystalꢀ
lized from AcOEt—hexane to give acid 1a or 1b as a brown solid
residue (90%). Compound 1a: m.p. 197.3—197.5 °C (cf. Ref. 16:
195—196 °C). Compound 1b: m.p. 185.5—186.1 °C (cf. Ref. 16:
186 °C).
Synthesis of phenylazides 2a—d containing (E)ꢀhalovinyl group
(general procedure). NꢀHalosuccinimide (1 mmol) in MeCN
(5 mL) was added dropwise to a stirred suspension of compound
1 (1.1 mmol) in MeCN—H2O (10 mL, 9 : 1, v/v) and LiOAc
(0.2 mmol). After addition of Nꢀhalosuccinimide was completꢀ
ed, the reaction mixture was stirred for 10 min at ~20 °C
(for NBS) or 1 h at 80 °C (for NIS and NCS). The solvent was
evaporated. The residue was diluted with AcOEt (30 mL) and
filtered. The filtrate was washed with brine (2×30 mL) and cold
water (30 mL) and dried with anhydrous Na2SO4. Crude prodꢀ
uct was obtained after evaporation of the solvent, which was
purified by column chromatography (silica gel, light petroleum)
to obtain phenylazide 2a—d.
were added to a stirred solution of phenylazide 2 (1 mmol) in
DMSO (5 mL). The reaction mixture was stirred for 12 h at ~20 °C
under nitrogen. The solvent was evaporated. The residue was
diluted with AcOEt (30 mL) and filtered. The filtrate was
washed with brine (2×30 mL) and cold water (30 mL) and
dried with anhydrous Na2SO4. Crude product was obtained after
evaporation of the solvent, which was purified by column
chromatography (silica gel, AcOEt—light petroleum) to obtain
triazole 3a—k.
Ethyl (E)ꢀ1ꢀ[4ꢀ(2ꢀbromovinyl)phenyl]ꢀ1,2,3ꢀtriazoleꢀ4ꢀcarbꢀ
oxylate (3a). Light yellow solid product, Rf 0.55 (AcOEt—light
petroleum, 1 : 4), m.p. 179.2—179.6 °C. Found (%): C, 48.44;
H, 3.73; Br, 24.83; N, 13.02. C13H12BrN3O2. Calculated (%):
C, 48.47; H, 3.75; Br, 24.80; N, 13.04. 1H NMR (500 MHz,
CDCl3), δ: 1.37 (t, 3 H, CH3, J = 7.0 Hz); 4.40 (q, 2 H, CH2, J =
= 7.0 Hz); 6.84 (d, 1 H, =CHBr, J = 14.0 Hz); 7.09 (d, 1 H,
ArCH=, J = 14.0 Hz); 7.42 (d, 2 H, Ar, J = 8.5 Hz); 7.67 (d, 2 H,
Ar, J = 8.5 Hz); 8.44 (s, 1 H, N=NꢀCH=). 13C NMR (125 MHz,
CDCl3), δ: 14.31, 61.55, 108.89, 121.06, 125.21, 127.46, 135.56,
135.79, 137.15, 140.97, 160.53.
(E)ꢀ{1ꢀ[4ꢀ(2ꢀBromovinyl)phenyl]ꢀ1,2,3ꢀtriazoleꢀ4ꢀyl}meꢀ
thanol (3b). White solid product, Rf 0.48 (AcOEt—light petroꢀ
leum, 1 : 5), m.p. 166.8—167.2 °C. Found (%): C, 47.11; H, 3.57;
Br, 28.56; N, 15.01. C11H10BrN3O. Calculated (%): C, 47.16;
H, 3.60; Br, 28.52; N, 15.00. 1H NMR (300 MHz, DMSOꢀd6),
δ: 4.71 (s, 2 H, CH2); 7.11 (d, 1 H, =CHBr, J = 14.0 Hz); 7.18
(d, 1 H, ArCH=, J = 14.0 Hz); 7.56 (d, 2 H, Ar, J = 9.0 Hz);
7.82 (d, 2 H, Ar, J = 9.0 Hz); 8.40 (s, 1 H, —N=NꢀCH=).
13C NMR (75 MHz, CDCl3), δ: 55.62, 108.69, 120.30, 120.44,
127.55, 135.78, 135.85, 136.53, 149.49.
(E)ꢀ1ꢀ[4ꢀ(2ꢀBromovinyl)phenyl]ꢀ4ꢀpentylꢀ1,2,3ꢀtriazole (3c).
White solid product, Rf 0.65 (AcOEt—light petroleum, 1 : 5),
m.p. 99.6—100.1 °C. Found (%): C, 56.22; H, 5.65; Br, 24.99;
N, 13.09. C15H18BrN3. Calculated (%): C, 56.26; H, 5.67; Br,
24.95; N, 13.12. 1H NMR (300 MHz, DMSOꢀd6), δ: 0.91 (t, 3 H,
CH3, J = 7.0 Hz); 1.24—1.26 (m, 2 H, CH3CH2); 1.23—1.40
(m, 4 H, (CH2)2); 1.72—1.77 (m, 2 H, CH2); 2.79 (t, 2 H, CH2,
J = 8.0 Hz); 6.86 (d, 1 H, =CHBr, J = 14.0 Hz); 7.17 (d, 1 H,
ArCH=, J = 14.0 Hz); 7.43 (d, 2 H, Ar, J = 8.5 Hz); 7.70 (d, 2 H,
Ar, J = 8.5 Hz); 7.71 (s, 1 H, N=N—CH=). 13C NMR (75 MHz,
CDCl3), δ: 13.95, 22.39, 25.60, 29.03, 31.04, 107.96, 118.47,
120.52, 127.24, 135.81, 135.98, 136.76, 149.34.
(E)ꢀ1ꢀAzidoꢀ4ꢀ(2ꢀbromovinyl)benzene (2a). Red liquid, Rf 0.85
(light petroleum). Found (%): C, 42.99; H, 2.81; Br, 35.31;
N, 18.90. C8H6BrN3. Calculated (%): C, 42.88; H, 2.70; Br,
1
35.66; N, 18.75. H NMR (500 MHz, CDCl3), δ: 6.66 (d, 1 H,
=CHBr, J = 14.0 Hz); 6.91 (d, 2 H, Ar, J = 8.5 Hz); 6.99 (d, 1 H,
ArCH=, J = 14.0 Hz); 7.21 (d, 2 H, Ar, J = 8.5 Hz). 13C NMR
(125 MHz, CDCl3), δ: 105.28, 118.38, 126.45, 131.77, 135.09,
138.86.
(E)ꢀ1ꢀAzidoꢀ2ꢀ(2ꢀbromovinyl)benzene (2b). Red liquid, Rf
0.80 (light petroleum). Found (%): C, 43.02; H, 2.85; Br, 35.20;
N, 18.93. C8H6BrN3. Calculated (%): C, 42.88; H, 2.70; Br,
1
35.66; N, 18.75. H NMR (500 MHz, CDCl3), δ: 6.86 (d, 1 H,
=CHBr, J = 14.0 Hz); 7.08—7.05 (m, 2 H, Ar); 7.30 (d, 1 H,
ArCH=, J = 14.0 Hz); 7.32—7.34 (m, 2 H, Ar). 13C NMR
(125 MHz, CDCl3), δ: 107.76, 117.64, 123.94, 126.39, 128.35,
131.31, 135.86.
(E)ꢀ1ꢀ[4ꢀ(2ꢀBromovinyl)phenyl]ꢀ4ꢀphenylꢀ1,2,3ꢀtriazole (3d).
Yellow solid product, m.p. 215.4—216.0 °C, Rf 0.70 (AcOEt—light
petroleum, 1 : 4). Found (%): C, 58.89; H, 3.70; Br, 24.56;
N, 12.85. C16H12BrN3. Calculated (%): C, 58.91; H, 3.71; Br, 24.50;
N, 12.88. 1H NMR (500 MHz, CDCl3), δ: 6.90 (d, 1 H, =CHBr,
J = 14.0 Hz); 7.16 (d, 1 H, ArCH=, J = 14.0 Hz); 7.37—7.49
(m, 5 H, Ar); 7.78 (d, 2 H, Ar, J = 8.5 Hz); 7.91 (d, 2 H, Ar,
J = 8.5 Hz); 8.19 (s, 1 H, N=N—CH=). 13C NMR (125 MHz,
CDCl3), δ: 108.28, 117.25, 120.73, 125.90, 127.38, 128.53,
128.95, 130.89, 135.79, 136.41, 136.57, 146.62.
(E)ꢀ1ꢀAzidoꢀ4ꢀ(2ꢀiodovinyl)benzene (2c). Purple liquid, Rf 0.87
(light petroleum). Found (%): C, 35.33; H, 2.06; I, 46.76; N,
15.79. C8H6IN3. Calculated (%): C, 35.45; H, 2.23; I, 46.82;
N, 15.50. 1H NMR (500 MHz, CDCl3), δ: 6.78 (d, 1 H, =CHI, J =
= 15.0 Hz); 6.96 (d, 2 H, Ar, J = 8.5 Hz); 7.27 (d, 2 H, Ar, J =
8.5 Hz); 7.37 (d, 1 H, Ar=CH, J = 15.0 Hz). 13C NMR (125 MHz,
CDCl3), δ: 76.23, 119.27, 127.34, 134.57, 139.93, 143.81.
(E)ꢀ1ꢀAzidoꢀ4ꢀ(2ꢀchlorovinyl)benzene (2d). Yellow liquid,
Rf 0.87 (light petroleum). Found (%): C, 53.65; H, 3.49; Cl, 19.30;
N, 23.51. C8H6ClN3. Calculated (%): C, 53.50; H, 3.37; Cl, 19.74;
N, 23.40. 1H NMR (500 MHz, CDCl3), δ: 6.59 (d, 1 H, =CHCl,
J = 14.0 Hz); 6.77 (d, 1 H, ArCH=, J = 14.0 Hz); 6.96 (d, 2 H, Ar,
J = 8.5 Hz); 7.21 (d, 2 H, Ar, J = 8.5 Hz). 13C NMR (125 MHz,
CDCl3), δ: 118.50, 119.36, 127.44, 131.68, 132.22, 139.71.
Synthesis of triazoles 3a—k (general procedure). Alkyne
(1.05 mmol), sodium ascorbate (0.15 mmol), and CuI (0.15 mmol)
(E)ꢀ1ꢀ[4ꢀ(2ꢀBromovinyl)phenyl]ꢀ4ꢀ(4ꢀbromophenyl)ꢀ1,2,3ꢀ
triazole (3e). Yellow solid product, Rf 0.50 (AcOEt—light petroꢀ
leum, 1 : 4), m.p. 206.3—206.9 °C. Found (%): C, 47.40; H, 2.72;
Br, 39.56; N, 10.33. C16H11Br2N3. Calculated (%): C, 47.44;
1
H, 2.74; Br, 39.45; N, 10.37. H NMR (300 MHz, DMSOꢀd6),
δ: 7.32 (d, 1 H, =CHBr, J = 14.0 Hz); 7.46 (d, 1 H, ArCH=,
J = 14.0 Hz); 7.72 (d, 2 H, Ar, J = 8.1 Hz); 7.75 (d, 2 H, Ar,
J = 8.1 Hz); 7.90 (d, 2 H, Ar, J = 8.5 Hz); 7.94 (d, 2 H, Ar,
J = 8.5 Hz); 9.38 (s, 1 H, N=N—CH=). 13C NMR (75 MHz,

Phenylꢀ1,2,3ꢀtriazoles bearing (E)ꢀ2ꢀhalovinyl group Russ.Chem.Bull., Int.Ed., Vol. 59, No. 2, February, 2010
455
CDCl3), δ: 109.41, 120.33, 121.63, 127.53, 127.85, 128.88,
129.81, 131.49, 132.09, 136.18, 136.37, 146.75.
H, 4.35; Cl, 12.81; N, 15.10. C13H12ClN3O2. Calculated (%):
C, 56.22; H, 4.36; Cl, 12.77; N, 15.13. 1H NMR (500 MHz,
CDCl3), δ: 1.44 (t, 3 H, CH3, J = 7.0 Hz); 4.47 (q, 2 H, CH2,
J = 7.0 Hz); 6.77 (d, 1 H, =CHCl, J = 14.0 Hz); 6.88 (d, 1 H,
ArCH=, J = 14.0 Hz); 7.48 (d, 2 H, Ar, J = 8.5 Hz); 7.74 (d, 2 H,
Ar, J = 8.5 Hz); 8.51 (s, 1 H, N=N—CH=). 13C NMR (125 MHz,
CDCl3), δ: 14.30, 61.52, 120.96, 121.04, 125.21, 127.46, 131.69,
135.72, 136.13, 140.94, 160.52.
(E)ꢀ4ꢀ{1ꢀ[4ꢀ(2ꢀBromovinyl)phenyl]ꢀ1,2,3ꢀtriazolꢀ4ꢀyl}ꢀNꢀ
phenylbenzenesulfonamide (3f). Yellow solid product, Rf 0.65
(AcOEt—light petroleum, 2 : 3), m.p. 247.2—247.7 °C. Found (%):
C, 54.84; H, 3.54; Br, 16.66; N, 11.61. C22H17BrN4O2S. Calcuꢀ
lated (%): C, 54.89; H, 3.56; Br, 16.60; N, 11.64. 1H NMR
(300 MHz, DMSOꢀd6), δ: 7.03—7.24 (m, 5 H, Ar); 7.32 (d, 1 H,
=CHBr, J = 14.0 Hz); 7.45 (d, 1 H, ArCH=, J = 14.0 Hz); 7.75
(d, 2 H, Ar, J = 8.7 Hz); 7.87 (d, 2 H, Ar, J = 8.7 Hz); 7.93 (d, 2 H,
Ar, J = 8.4 Hz); 8.08 (d, 2 H, Ar, J = 8.4 Hz); 9.43 (s, 1 H,
N=NꢀCH=). 13C NMR (75 MHz, CDCl3), δ: 110.14, 120.73,
120.81, 121.42, 124.66, 126.23, 128.04, 128.20, 129.61, 134.73,
136.03, 136.31, 136.59, 138.07, 139.28, 146.24.
(E)ꢀ4ꢀ{1ꢀ[4ꢀ(2ꢀBromovinyl)phenyl]ꢀ1,2,3ꢀtriazolꢀ4ꢀyl}ꢀNꢀ
methylꢀNꢀphenylbenzenesulfonamide (3g). Light yellow solid
product, Rf 0.50 (AcOEt—light petroleum, 1 : 2), m.p.
201.3—201.8 °C. Found (%): C, 55.71; H, 3.79; Br, 16.25;
N, 11.27. C23H19BrN4O2S. Calculated (%): C, 55.76; H, 3.87;
Br, 16.13; N, 11.31. 1H NMR (500 MHz, CDCl3+ DMSOꢀd6),
δ: 3.25 (s, 3 H, CH3); 6.95 (d, 1 H, =CHBr, J = 14.0 Hz);
7.11—7.12 (m, 2 H, Ar); 7.18 (d, 1 H, ArCH=, J = 14.0 Hz);
7.29—7.34 (m, 3 H, Ar); 7.52 (d, 2 H, Ar, J = 8.5 Hz); 7.62
(d, 2 H, Ar, J = 8.5 Hz); 7.83 (d, 2 H, Ar, J = 8.5 Hz); 8.04
(d, 2 H, Ar, J = 8.5 Hz); 8.61 (s, 1 H, N=NꢀCH=). 13C NMR
(125 MHz, CDCl3), δ: 29.30, 108.50, 119.33, 120.57, 125.82,
126.52, 127.40, 128.35, 128.87, 134.72, 135.63, 136.18, 136.43,
137.69, 138.17, 141.25, 146.51.
Ethyl (E)ꢀ1ꢀ[2ꢀ(2ꢀbromovinyl)phenyl]ꢀ1,2,3ꢀtriazoleꢀ4ꢀcarbꢀ
oxylate (3h). Brown oil, Rf 0.45 (AcOEt—light petroleum, 1 : 3).
Found (%): C, 48.42; H, 3.74; Br, 24.88; N, 13.03. C13H12BrN3O2.
Calculated (%): C, 48.47; H, 3.75; Br, 24.80; N, 13.04. 1H NMR
(500 MHz, CDCl3), δ: 1.45 (t, 3 H, CH3, J = 7.0 Hz); 4.48
(q, 2 H, CH2, J = 7.0 Hz); 6.84 (s, 2 H, =CH); 7.41 (d, 1 H, Ar,
J = 7.5 Hz); 7.50—7.55 (m, 2 H, Ar); 7.61 (d, 1 H, Ar, J = 7.5 Hz);
8.31 (s, 1 H, N=N—CH=). 13C NMR (125 MHz, CDCl3), δ:
14.24, 61.50, 111.30, 126.39, 127.16, 129.20, 129.33, 130.75,
130.96, 131.83, 133.37, 140.45, 160.44.
(E)ꢀ{1ꢀ[2ꢀ(2ꢀBromovinyl)phenyl]ꢀ1,2,3ꢀtriazolꢀ4ꢀyl}methꢀ
anol (3i). Brown oil, Rf 0.55 (AcOEt—light petroleum, 1 : 2).
Found (%): C, 47.12; H, 3.58; Br, 29.08; N, 15.02. C11H10BrN3O.
Calculated (%): C, 47.16; H, 3.60; Br, 28.52; N, 15.00. 1H NMR
(500 MHz, CDCl3), δ: 4.85 (s, 2 H, CH2); 6.72 (d, 1 H, =CHBr,
J = 14.0 Hz); 6.81 (d, 1 H, ArCH=, J = 14.0 Hz); 7.31—7.50
(m, 4 H, Ar); 7.71 (s, 1 H, N=N—CH=). 13C NMR (125 MHz,
CDCl3), δ: 56.16, 110.57, 123.99, 126.42, 127.00, 129.09, 130.15,
131.47, 131.64, 134.14, 147.97.
The authors are grateful to the Center of Instrumental
Analysis of Tongji University (China).
This work was financially supported by the Natural
Science Fund of China (Grant 30873153), the Natural
Science Fund of Shanghai (Grant 06ZR14085) and the
Fund of Scientific Studies of the Ministry of Education
for the Support of Chinese Grantꢀaided Students Returned
from Abroad.
References
1. K. Barral, A. D. Moorhouse, J. E. Moses, Org. Lett., 2007, 9,
1809; S. Bräse, C. Gil, K. Knepper, V. Zimmermann, Anꢀ
gew. Chem., Int. Ed., 2005, 44, 5188; E. F. V. Scriven,
K. Turnbull, Chem. Rev., 1988, 88, 297.
2. H. Bayley, J. V. Staros, in Azides and Nitrenes, Ed. E. F. V.
Scriven, Academic Press, Orlando, 1984, 433; A. Radominsꢀ
ka, R. R. Drake, Methods Enzymol., 1994, 230, 330; J. S.
Fedan, G. K. Hogaboom, J. P. O´Donnell, Biochem. Pharꢀ
macol., 1984, 33, 1167.
3. A. R. Katritzky, Y. Zhang, S. K. Singh, Heterocycles, 2003,
60, 1225.
4. C. W. Tornøe, C. Christensen, M. J. Meldal, J. Org. Chem.,
2002, 67, 3057; V. V. Rostovtsev, L. G. Green, V. V. Fokin,
K. B. Sharpless, Angew. Chem., Int. Ed., 2002, 41, 2596.
5. H. C. Kolb, K. B. Sharpless, Drug Discov. Today, 2003,
8, 1128.
6. P. Wu, A. K. Feldman, A. K. Nugent, C. J. Hawker,
A. Scheel, B. Voit, J. Pyun, J. M. J. Frechet, K. B. Sharpless,
V. V. Fokin, Angew. Chem., Int. Ed., 2004, 43, 3928;
B. Helms, J. L. Mynar, C. J. Hawker, J. M. J. Frechet, J. Am.
Chem. Soc., 2004, 126, 15020; A. Scheel, H. Komber, B. Voit,
Macromol. Rapid Commun., 2004, 25, 1175; M. Parent,
O. Mongin, K. Kamada, C. Katan, M. BlanchardꢀDesce,
Chem. Commun., 2005, 2029; D. J. V. C. van Steenis, O. R.
P. David, G. P. F. van Strijdonck, J. H. van Maarseveen,
J. N. H. Reek, Chem. Commun., 2005, 4333.
Ethyl (E)ꢀ1ꢀ[4ꢀ(2ꢀiodovinyl)phenyl]ꢀ1,2,3ꢀtriazoleꢀ4ꢀcarbꢀ
oxylate (3j). Light yellow solid product, Rf 0.55 (AcOEt—light
petroleum, 1 : 4), m.p. 187.1—187.4 °C. Found (%): C, 42.25;
H, 3.26; I, 34.42; N, 11.36. C13H12IN3O2. Calculated (%):
C, 42.30; H, 3.28; I, 34.38; N, 11.38. 1H NMR (500 MHz, CDCl3),
δ: 1.44 (t, 3 H, CH3, J = 7.0 Hz); 4.47 (q, 2 H, CH2, J = 7.0 Hz);
7.02 (d, 1 H, =CHI, J = 15.0 Hz); 7.47 (d, 2 H, Ar, J = 8.5 Hz);
7.48 (d, 1 H, ArCH=, J = 15.0 Hz); 7.74 (d, 2 H, Ar, J = 8.5 Hz);
8.52 (s, 1 H, N=N—CH=). 13C NMR (125 MHz, CDCl3), δ:
14.28, 61.50, 79.23, 120.91, 125.19, 127.31, 135.77, 138.72,
140.91, 143.22, 160.48.
7. S. Löber, P. RodriguezꢀLoaiza, P. Gmeiner, Org. Lett., 2003,
5, 1753; K. Harju, M. Vahermo, I. Mutikainen, J. YliꢀKauꢀ
haluoma, J. Comb. Chem., 2003, 5, 826; B. Khanetskyy,
D. Dallinger, C. O. Kappe, J. Comb. Chem., 2004, 6, 884;
C. W. Tornoe, S. J. Sanderson, J. C. Mottram, G. H. Coombs,
M. Meldal, J. Comb. Chem., 2004, 6, 312.
8. M. J. Genin, D. A. Allwine, D. J. Anderson, M. R. Barꢀ
bachyn, D. E. Emmert, S. A. Garmon, D. R. Graber, K. C.
Grega, J. B. Hester, D. K. Hutchinson, J. Morris, R. D.
Reischer, D. Stper, B. H. Yagi, J. Med. Chem., 2000, 43, 953.
9. H. Wamhoff, in Comprehensive Heterocyclic Chemistry, Eds
A. R. Katritzky, C. W. Rees, Pergamon, Oxford, 1984, 669.
10. D. R. Buckle, C. J. M. Rockell, H. Smith, B. A. Spicer,
J. Med. Chem., 1986, 29, 2262.
Ethyl (E)ꢀ1ꢀ[4ꢀ(2ꢀchlorovinyl)phenyl]ꢀ1,2,3ꢀtriazoleꢀ4ꢀcarbꢀ
oxylate (3k). Light yellow solid product, Rf 0.65 (AcOEt—light
petroleum, 1 : 4), m.p. 161.3—162.7 °C. Found (%): C, 56.20;

456
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 2, February, 2010
Zhang et al.
11. R. Alvarez, S. Velazquez, A. SanꢀFelix, S. Aquaro, E. De
Clercq, C. F. Perno, A. Karlsson, J. Balzarini, M. J. Camaꢀ
rasa, J. Med. Chem., 1994, 37, 4194.
12. F. A. Davis, G. S. Lal, J. Wei, Tetrahedron Lett., 1988,
29, 4269.
15. J. McNulty, J. A. Steere, S. Wolf, Tetrahedron Lett., 1998,
39, 8013.
16. K. A. N. Rao, P. R. Venkataraman, J. Indian Chem. Soc.,
1938, 15, 194.
13. J. Tsuji, Palladium Reagent and Catalysts, Innovations in
Organic Synthesis, Wiley, Chichester, 1995; F. Diederich,
P. J. Stang, MetalꢀCatalyzed CrossꢀCoupling Reactions, Wiꢀ
ley—VCH, Weinheim, 1998.
14. C. Kuang, Q. Yang, H. Senboku, M. Tokuda, Synthesis, 2005,
8, 1319.
Received February 3, 2009;
in revised form May 4, 2009