Utility of allylic azides for the synthesis of fused triazoles and tetrazoles via intramolecular cycloaddition

Article abstract of DOI:10.1055/s-0029-1218847

The synthesis of a variety of annulated triazoles and tetrazoles from differently substituted allyl azides, afforded from the Baylis-Hillman adduct of acrylates, using intramolecular cycloaddition approach is described. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1218847

PAPER
2731
Utility of Allylic Azides for the Synthesis of Fused Triazoles and Tetrazoles via
Intramolecular Cycloaddition1
F
use
d
T
riazoles an
m
d
T
etrazoles via Int
i
ramole
c
ular
Ca
ycloaddition Mishra,a Samiran Hutait,a Subhendu Bhowmik,a Neeraj Rastogi,b Raja Roy,b Sanjay Batra*a
a
Medicinal and Process Chemistry Division, Central Drug Research Institute, PO Box 173, Lucknow 226001, India
Centre of Biomedical Magnetic Resonance, Sanjay Gandhi Post-Graduate Institute of Medical Sciences Campus, Raebareli Road,
Lucknow 226 014 UP, India
b
Fax +91(522)2623405; fax +91(522)2623938; E-mail: batra_san@yahoo.co.uk
Received 6 April 2010
within 30 minutes. The alcohol 3f was reacted with prop-
argyl bromide in the presence of sodium hydride to yield
4f, which then served as the substrate for intramolecular
dipolar cycloaddition. Unfortunately, 4f was found to be
unstable and, therefore, it was subjected to further reac-
tion without purification. Refluxing compound 4f in tolu-
ene for five hours furnished a mixture of two products
which were separated via a careful column chromatogra-
phy. Based on the spectral analysis, we expected these
compounds to be the E- and Z-isomers of the expected an-
nulated triazole 5f. In order to confirm the assigned struc-
ture and investigate the relative stereochemistry of these
two products, detailed NMR experiments were per-
Abstract: The synthesis of a variety of annulated triazoles and tet-
razoles from differently substituted allyl azides, afforded from the
Baylis–Hillman adduct of acrylates, using intramolecular cycload-
dition approach is described.
Key words: Baylis–Hillman, allyl azide, cycloaddition, triazole,
tetrazole
Recent times have witnessed a stupendous increase in the
number of applications of azide derivatives for the synthe-
sis of a plethora of 1,2,3-triazole derivatives; this is be-
cause they are of use in several spheres including
bioconjugation,2 material,3 and medicinal chemistry.4
Generally, syntheses of 1,2,3-triazoles have been
achieved either through Husigen5 or click reactions.6 Due
to the importance of triazoles and their annulated ana-
logues, investigations with newer substrates to accom-
plish the synthesis of diverse derivatives is an active area
of research. We have been interested in the synthesis of
heterocycles from intermediates offered via Baylis–
Hillman chemistry and during the course of this program
we became interested in the synthesis of annulated 1,2,3-
triazoles. The literature includes several strategies for ob-
taining triazoles using Baylis–Hillman derivatives, which
essentially employ intramolecular or intermolecular cy-
cloaddition reactions.7 We, thus, embarked on an intramo-
lecular cycloaddition approach wherein we utilized the
ester moiety to obtain the acetylene or the azide unit for
the synthesis of [1,2,3]triazolo[5,1-c][1,4]oxazepines and
[1,2,3]triazolo[1,5-a][1,4]diazepines. During the course
of the study it became apparent that substrates generated
in this work could be extended for the synthesis of an an-
nulated tetrazole system through the cycloaddition reac-
tion. We report results of our studies in this direction.
1
formed. Combined application of H, 13C, and 2D NMR
(viz. HSQC, HMBC, and NOESY) spectra revealed that
the less polar compound was the E-isomer (E)-5f
(Figure 1) whereas the polar analogue was the Z-isomer of
(Z)-5f (Figure 2).
OAc
CO2Me
CH2OH
iii
70–83%
R
R
i
ii
CO2Me
R
68–86%
85–90%
N3
2a–i
N3
3a–i
1a–i
O
O
R
CH2O
N3
+
iv
R
R
N
N
N
N
N
N
E
5a–i
Z
4a–i
vi
47–81%
26–46%
vi
v
O
N
7a,f
O
Ph
90–95%
R
N
N
N
N
N
6a
89%
7a,f
Synthesis
of
7-benzylidene-4,6,7,8-tetrahy-
49–50%
dro[1,2,3]triazolo[5,1-c][1,4]oxazepine: We initiated
our study with the synthesis of allyl azides via an earlier
reported procedure.8 We selected azide 2f to optimize the
reaction conditions (Scheme 1). Reduction of the ester
group in 2f with diisobutylaluminum hydride smoothly
produced the alcohol 3f stereoselectively as the E-isomer
+
(Z)-5a,f
Scheme 1 Reagents and conditions: (i) NaN3, DABCO, THF–H2O,
r.t., 2 min; (ii) DIBAL-H, toluene, 0 °C to r.t., 30 min; (iii) propargyl
bromide, NaH, THF, r.t., 2 h; (iv) toluene, 90 °C, 5–7 h; (v) 10% Pd/C,
MeOH, 50 psi, r.t., 2 h; (vi) DBU, THF, 80 °C, 24 h. (For key to R
refer to Table 1.)
SYNTHESIS 2010, No. 16, pp 2731–2748
Advanced online publication: 29.06.2010
DOI: 10.1055/s-0029-1218847; Art ID: P05410SS
x
x.
x
x
.
2
0
1
0
In order to assess the general applicability of our protocol
several azides 2a–e,g–i were subjected to a similar se-
© Georg Thieme Verlag Stuttgart · New York

2732
A. Mishra et al.
PAPER
Table 1 Crude Products 5; Yields and E/Z Ratio (1H NMR)
6
O 5
7
O
7'
4
1'
Crude product
R
Yield (%)
Ratioa E/Z
3a
8
N
N
N
2'
3
8a
5a
5b
5cb
5d
5e
Ph
97
92
90
88
90
96
71
81
83
52:48
53:47
60: 40
50: 50
56: 44
56: 44
100:0
100:0
58: 42
4'
N
N
1
3'
N
2
2-ClC6H4
2-FC6H4
4-ClC6H4
4-FC6H4
4-MeC6H4
2,4-Cl2C6H3
2,6-Cl2C6H3
2-thienyl
HMBC correlations
NOESY correlations
Figure 1 (1) (E)-5f with numbering. (2) Selected correlations in
HMBC and NOESY spectra of 5f.
5f
4'
3'
5g
5h
5ib
2'
5
O
6
O
1'
7'
4
7
3a
3
8
N
N
N
8a N
1
N
a Ratio of diastereomers based on 1H NMR of crude product.
b Diastereomers could not be separated via column chromatography.
2
N
HMBC correlations
NOESY correlations
sulfonamide.10 Treatment of 8a with propargyl bromide in
the presence of sodium hydride gave 9a (Scheme 2). Re-
duction of the ester group in 9a with diisobutylaluminum
hydride followed by sequential mesylation and azidation
yielded the required substrate 12a. Cycloaddition reaction
by heating 12a in toluene resulted in a mixture of two
products. These products were separated via column chro-
matography in 55% and 40% yields and established to be
the E- and Z-isomers, respectively, of the expected tria-
zolodiazepine 13a. The scope of the protocol was studied
by subjecting different substrates 8c,d,f,g to a similar se-
ries of reactions (Scheme 2, Table 2). Interestingly here
also reaction for substrate 8g with a 2,4-dichlorophenyl
group was observed to be highly stereoselective to afford
(E)-13g exclusively. Subsequently the effect of DBU on
(E)-13g was examined. In contrast to results achieved
with 5, here the isomerization reaction produced two
products which were identified as 14g and 15g. Although
it is known that under the influence of base detosylation
occurs,11 we did not observe the formation of detosylated
product during this reaction.
Figure 2 (1) (Z)-5f with numbering. (2) Selected correlations in
HMBC and NOESY spectra of 5f.
quence of reactions (Scheme 1, Table 1). Notably howev-
er we discovered that the stereoselectivity of the products
obtained via cyclization was influenced by the substitu-
tion present on the phenyl ring (5g and 5h, Table 1). To
provide chemical support for the existence of 5a–f,i as a
mixture of E- and Z-isomers, in a representative experi-
ment, (E/Z)-5a was subjected to catalytic hydrogenation
in the presence of palladium-on-carbon to afford 6a in
92% yield. Alternatively, treatment of (E/Z)-5a with DBU
was expected to furnish a single product due to isomeriza-
tion of the double bond.9 Therefore, (E/Z)-5f was treated
with DBU under heating at reflux. Unexpectedly, this re-
action yielded a mixture of two products, which were es-
tablished to be 7f and (Z)-5f. This result implied that in the
presence of DBU, the (E)-5f undergoes isomerization to
afford 7f but (Z)-5f is unaffected. Further experimental
support to this observation was gained via another set of
experiments wherein (E)-5f and (Z)-5f were independent-
ly treated with DBU. It was observed that (E)-5f under-
went smooth isomerization to produce 7f in four hours
whereas (Z)-5f remained unaffected (16 h). Study with an-
other set of isomers of 5a gave similar results to afford a
mixture of 7a and (Z)-5a, which were readily separated.
This finding inferred that in these compounds the isomer-
ization is favored in the E-isomer as compared to the Z-
isomer.
Table 2 Crude Products 13; Yields and E/Z Ratio (1H NMR)
Crude product
R
Yield (%)
Ratioa E/Z
58:42
13a
13c
13d
13f
13g
Ph
95
85
94
90
83
2-FC6H4
4-ClC6H4
4-MeC6H4
2,4-Cl2C6H3
90:10
57:43
50:50
Synthesis
of
7-Arylidene-5,6,7,8-tetrahydro-4H-
This success
100:0
[1,2,3]triazolo[1,5-a][1,4]diazepine:
a For isolated yields of 13 (E and Z) refer to the experimental section.
prompted us to investigate a similar strategy for another
allyl azide that could be generated from the allylamine of
adduct of acrylate. For this sequence the optimization
study was carried out using 1a. Initially, tosyl derivative
8a was obtained via reaction between 1a and 4-toluene-
Application of the protocol was further investigated using
allylamine 16. Treatment of 1g with 4-toluenesulfon-
amide in the presence of DABCO under aqueous condi-
Synthesis 2010, No. 16, 2731–2748 © Thieme Stuttgart · New York

PAPER
Fused Triazoles and Tetrazoles via Intramolecular Cycloaddition
2733
solely as the E-isomer (Scheme 3, Table 3). Subsequent-
ly, in a representative reaction, treatment of 23g with
DBU resulted in the formation of a mixture of 25g and
26g. In order to create the more diversity benzylamine
was replaced by propylamine to synthesize 20a,e–h. A
similar set of reactions produced 24a,e–h in good yields.
OAc
R
NHTs
TsN
i
ii
CO2Me
CO2Me
CO2Me
R
80%
R
1a,c,d,f,g
16g
17g
iv
75-80%
CO2Me
iii
CO2Me
NTs
CH2OH
NTs
R
iii
70–83%
ii
69-91%
CH2OMs
CH2OH
NHR2
R1
R1
R1
ii
i
R
R
NHTs
85–90%
N3
75–89%
N3
N3
3a,e–h
19a,e–h R2 = Bn
8a,c,d,f,g
9a,c,d,f,g
10a,c,d,f,g
18a,e–h
20a,e–h R2 = Pr
v
R1
NR2
N
R1
NR2
CN
N
iv
v
iii
74–88%
N
R
CH2OMs
NTs
CH2N3
NTs
12a,c,d,f,g
N
N
87% (1:1)
N
75–95%
vii
vi
N3
N
N
R
R
21a,e–h R2 = Bn
22a,e–h R2 = Pr
23a,e–h R2 = Bn
Ts
24a,e–h R2 = Pr
viii
E
11a,c,d,f,g
42–83%
R1
NR2
R1
NR2
R
+
N
N
N
+
N
N
N
N
N
N
N
N
N
N
N
N
R
R
+
N
N
N
N
26g
25g
N
Ts
Ts
Ts
Scheme 3 Reagents and conditions: (i) MsCl, Et3N, CH2Cl2, r.t., 30
min; (ii) R2NH2, KI, THF, 80 °C, 2 h; (iii) CNBr, NaHCO3, MeOH,
r.t., 15 min; (iv) DMF, 90 °C, 2 h; (v) DBU, THF, 80 °C, 24 h (For
key to R1 and R2 refer to Table 3.)
Z
14g
15g
7–42%
13a,c,d,f,g
Scheme 2 Reagents and conditions: (i) TsNH2, DABCO, THF–
H2O, r.t., 2 h; (ii) propargyl bromide, K2CO3, DMF, r.t., 2 h; (iii)
DIBAL-H, toluene, 0 °C to r.t., 30 min; (iv) TsNH2, K2CO3, THF, 75
°C, 2 h; (v) MsCl, Et3N, CH2Cl2, 0 °C to r.t., 30 min; (vi) NaN3, DMF,
r.t., 1 h; (vii) toluene, reflux, 6–7 h; (viii) DBU, THF, 80 °C, 24 h.
(For key to R refer to Table 2.)
Table 3 Products; Isolated Yields and E/Z Ratio (1H NMR)a
Product
23a
23e
R1
R2
Bn
Bn
Bn
Bn
Bn
Pr
Yield (%) Ratio E/Z
Ph
76
88
86
88
93
86
86
84
83
85
67:33
54:46
71:29
100:0
100:0
67:33
67:33
58:42
68:32
100:0
4-FC6H4
4-MeC6H4
2,4-Cl2C6H3
2,6-Cl2C6H3
Ph
tions gave the tosyl derivative 16g (Scheme 2).
Substituting the NH group in 16g with propargyl bromide
afforded the tertiary amide 17g. Reducing the ester group
in 17g with diisobutylaluminum hydride, however, result-
ed in formation of 10g instead of the expected alcohol.
23f
23g
23h
24a
24e
Synthesis of 6-Arylidene-4-alkyl-4,5,5,6-tetrahydro-
tetraazolo[1,5-a]pyrimidines: Based on our previous ex-
perience with N-allylcyanamides,12 it occurred to us that
substrates afforded during this endeavor can be employed
to achieve the synthesis of annulated tetrazoles. Tetra-
zoles are another important class of molecule that have
found significant application as pharmacological agents.13
Accordingly, an optimization study with 3f was initiated.
Reacting 3f with mesyl chloride in the presence of trieth-
ylamine in dichloromethane afforded the mesyl derivative
18f (Scheme 3). Substituting mesyl group with benzyl-
amine produced secondary amine 19f in 77% yield. Com-
pound 19f was readily transformed to cyanamide 21f by
reaction with cyanogen bromide in the presence of sodium
hydrogen carbonate in methanol. Heating 21f in N,N-di-
methylformamide at 90 °C for two hours yielded the an-
nulated tetrazole 23f as a mixture of E- and Z-isomers.
Despite several attempts, both the isomers in this case
could not be separated. The protocol was found to be gen-
eral over several substrates and here too the 2,4-dichlo-
rophenyl or 2,6-dichlorophenyl groups furnished products
4-FC6H4
4-MeC6H4
2,4-Cl2C6H3
2,6-Cl2C6H3
Pr
24f
Pr
24g
Pr
24h
Pr
a The isomers are inseparable.
Though benzylamine and propylamine worked well for
the strategy, the reaction of 4-toluenesulfonamide with the
mesylate 18 did not proceed smoothly forcing us explore
an alterative route. As a consequence the alcohol 3f was
transformed into allyl bromide 27f by reaction with phos-
phorus tribromide in dichloromethane. Substitution reac-
tion of 27f with 4-toluenesulfonamide proceeded
smoothly to yield allyl azide 28f (Scheme 4). The reaction
of cyanogen bromide in the presence of sodium hydride
resulted in the formation of cyanamide 29f, which on
Synthesis 2010, No. 16, 2731–2748 © Thieme Stuttgart · New York

2734
A. Mishra et al.
PAPER
were performed on a Carlo Erba 108 or an Elementar Vario EL III
microanalyzer.
heating in N,N-dimethylformamide at 90 °C readily yield-
ed (E)-30f exclusively. This protocol was also found to be
of a general nature as evident from the preparation of
30a,e and 30g also. For this set of compounds, 30e and
30g were obtained as a mixture of E- and Z-isomers which
could not be separated, but 30a was isolated as the E-iso-
mer exclusively (Scheme 4, Table 4).
(E)-2-(Azidomethyl)-3-phenylprop-2-en-1-ol (3a); Typical Pro-
cedure for 3a–i, 10a,c,d,f,g
To a stirred soln of 2a (2.10 g, 9.68 mmol) in toluene (50 mL), was
added 1.0 M DIBAL-H in toluene (19.36 mL, 19.36 mmol) at 0 °C
under N2. The mixture was stirred at r.t. for 30 min (TLC monitor-
ing). When the reaction was complete, it was quenched with MeOH
(30 mL) and the separated precipitate was filtered through Celite.
The filtrate was evaporated to afford the crude product as oil. Puri-
fication by column chromatography (silica gel, 100–200 mesh,
EtOAc–hexanes, 1:4) furnished 3a (1.51 g, 83%) as reddish brown
oil; Rf = 0.30 (EtOAc–hexanes, 1:4).
CH2OH
CH2Br
NHTs
R
R
R
i
ii
45–60%
80–90%
N3
N3
N3
3a,e–g
27a,e–g
28a,e–g
IR (neat): 2102 (N3), 3443 cm–1 (OH).
R
NTs
R
NTs
CN
iv
1H NMR (300 MHz, CDCl3): d = 1.79 (s, 1 H, OH), 4.10 (s, 2 H,
CH2), 4.35 (d, J = 1.1 Hz, 2 H, CH2), 6.83 (s, 1 H, =CH), 7.23–7.32
(m, 3 H, ArH), 7.35–7.40 (m, 2 H, ArH).
13C NMR (75 MHz, CDCl3): d = 48.8, 65.9, 127.6, 128.5, 128.8,
131.2, 132.1, 135.3, 135.7.
iii
N
75–90%
75–90%
N
N
N3
29a,e–g
N
30a,e–g
Scheme 4 Reagents and conditions: (i) PBr3, CH2Cl2, 0 °C to r.t.,
30 min; (ii) TsNH2, NaH, DMF, r.t., 2 h; (iii) CNBr, NaH, CH2Cl2, 2
h; (iv) DMF, 90 °C, 2 h. (For key to R refer to Table 4.)
MS (ES+): m/z = 190.0 [M+ + 1].
Anal. Calcd for C10H11N3O: C, 63.48; H, 5.86; N, 22.21. Found: C,
63.46; H, 5.74; N, 22.18.
Table 4 Crude Products 30; Yields and E/Z Ratio (1H NMR)a
(E)-2-(Azidomethyl)-3-(2-chlorophenyl)prop-2-en-1-ol (3b)
Colorless oil; yield: 0.71 g (80%); Rf = 0.33 (EtOAc–hexanes, 1:4).
IR (neat): 2101 (N3), 3487 (OH) cm–1.
1H NMR (300 MHz, CDCl3,): d = 3.99 (s, 2 H, CH2), 4.38 (d, J =
1.1 Hz, 2 H, CH2), 6.83 (s, 1 H, =CH), 7.23–7.28 (m, 3 H, ArH),
7.34–7.43 (m, 2 H, ArH).
Product
30a
R
Yield (%)
Ratio E/Z
100:0
Ph
80
76
78
84
30e
4-FC6H4
4-MeC6H4
2,4-Cl2C6H3
67:33
30f
100:0
13C NMR (CDCl3, 75 MHz): d = 48.8, 65.2, 117.8, 126.7, 127.9,
129.1, 129.6, 130.5, 134.2, 137.2.
30g
71:29
MS (ES+): m/z = 224.1 (M+ + 1).
a The isomers are inseparable.
Anal. Calcd for C10H10ClN3O: C, 53.70; H, 4.51; N, 18.79. Found:
C, 53.68; H, 4.62; N, 18.82.
In summary we have developed a synthesis of new annu-
lated triazole and tetrazole derivatives from different allyl
azides afforded from Baylis–Hillman chemistry. This fur-
ther demonstrates the synthetic utility of Baylis–Hillman
derivatives for heterocyclic synthesis. Moreover the work
presented here shows that the diastereoselectivity of the
afforded annulated triazoles was influenced by the nature
of substitutions present on the aromatic ring present in the
molecule. Moreover it was observed that the isomeriza-
tion of the exocyclic double bond in products synthesized
herein is influenced by the stereochemistry. All com-
pounds reported in this study were evaluated for antimi-
crobial activity, but no significant activity was detected.
(E)-2-(Azidomethyl)-3-(2-fluorophenyl)prop-2-en-1-ol (3c)
Brown oil; yield: 1.00 g (76%); Rf = 0.35 (EtOAc–hexanes, 1:4).
IR (neat): 2106 (N3), 3483 (OH) cm–1.
1H NMR (200 MHz, CDCl3): d = 1.80 (s, 1 H, OH), 3.97 (s, 2 H,
CH2), 4.39 (s, 2 H, CH2), 6.77 (s, 1 H, =CH), 7.17–7.29 (m, 3 H,
ArH), 7.43 (m, 1 H, ArH).
13C NMR (CDCl3, 50 MHz): d = 49.4, 65.6, 127.3, 127.6, 129.8,
129.9, 131.6, 133.1, 134.8, 135.2, 138.5.
MS (ES+): m/z = 208.1 (M+ + 1).
Anal. Calcd for C10H10FN3O: C, 57.97; H, 4.86; N, 20.28. Found:
C, 58.25; H, 4.92; N, 20.40.
(E)-2-(Azidomethyl)-3-(4-chlorophenyl)prop-2-en-1-ol (3d)
Orange oil; yield: 0.15 g (68%); Rf = 0.25 (EtOAc–hexanes, 1:4).
IR (neat): 2102 (N3), 3439 cm–1 (OH).
1H NMR (200 MHz, CDCl3): d = 1.70 (s, 1 H, OH), 4.05 (s, 2 H,
CH2), 4.34 (s, 2 H, CH2), 6.76 (s, 1 H, =CH), 7.17 (d, J = 8.4 Hz, 2
H, ArH), 7.34 (d, J = 8.5 Hz, 2 H, ArH).
13C NMR (50 MHz, CDCl3): d = 49.0, 66.1, 129.0, 129.1, 129.4,
130.2, 130.5, 134.0, 134.5, 136.5.
MS (ES+): m/z = 224.0 [M+ + 1].
Melting points are uncorrected and were determined in capillary
tubes on an apparatus containing silicon oil. IR spectra were record-
ed using a Perkin Elmer’s RX I FTIR spectrophotometer. 1H and 13
C
NMR spectra were recorded on either a Bruker DPX-200 FT, a
Bruker Avance DRX-300 or a Bruker Avance 400 spectrometer, us-
ing TMS as an internal standard. The 13C NMR spectra of fluoro de-
rivatives contain more signals due to carbon–fluoro coupling.
Representative spectral data for compounds 4 are provided, as these
compounds were found to have a short shelf-life. ESMS were re-
corded on a Micromass Quadro-II LCMS system. HRMS spectra
were recorded as EI-HRMS on a Jeol system. Elemental analyses
Anal. Calcd for C10H10ClN3O: C, 53.70; H, 4.51; N, 18.79. Found:
C, 53.79; H, 4.42; N, 18.82.
Synthesis 2010, No. 16, 2731–2748 © Thieme Stuttgart · New York

PAPER
Fused Triazoles and Tetrazoles via Intramolecular Cycloaddition
2735
(E)-2-(Azidomethyl)-3-(4-fluorophenyl)prop-2-en-1-ol (3e)
Brown oil; yield: 1.02 g (68%); Rf = 0.35 (EtOAc–hexanes, 1:4).
Anal. Calcd for C8H9N3OS: C, 49.21; H, 4.65; N, 21.52. Found: C,
49.01; H, 4.72; N, 21.48.
IR (neat): 2103 (N3), 3481 cm–1 (OH).
(E)-3-Phenyl-2-{[(prop-2-ynyl)tosylamino]methyl}prop-2-en-1-
ol (10a)
White solid; yield: 1.50 g (74%); mp 85–87 °C; Rf = 0.27 (EtOAc–
hexanes, 1:4).
1H NMR (200 MHz, CDCl3): d = 1.84 (s, 1 H, OH), 4.07 (s, 2 H,
CH2), 4.35 (s, 2 H, CH2), 6.78 (s, 1 H, =CH), 7.02–7.10 (m, 2 H,
ArH), 7.19–7.22 (m, 2 H, ArH).
13C NMR (50 MHz, CDCl3): d = 49.2, 65.5, 127.1, 127.5, 129.8,
129.9, 131.6, 133.1, 134.7, 135.0, 138.3.
IR (KBr): 3304 (≡CH), 3420 cm–1 (OH).
1H NMR (300 MHz, CDCl3): d = 1.75 (t, J = 2.4 Hz, 1 H, ≡CH),
2.41 (s, 3 H, CH3), 2.84 (s, 1 H, OH), 4.00 (d, J = 2.3 Hz, 2 H, CH2),
4.06 (s, 2 H, CH2), 4.33 (s, 2 H, CH2), 6.84 (s, 1 H, =CH), 7.15 (d,
J = 7.0 Hz, 2 H, ArH), 7.21–7.30 (m, 5 H, ArH), 7.69 (d, J = 8.3 Hz,
2 H, ArH).
MS (ES+): m/z = 208.1 [M+ + 1].
Anal. Calcd for C10H10FN3O: C, 57.97; H, 4.86; N, 20.28. Found:
C, 58.22; H, 4.73; N, 20.44.
13C NMR (75 MHz, CDCl3): d = 21.6, 36.3, 43.1, 64.7, 73.9, 76.1,
(E)-2-(Azidomethyl)-3-(4-methylphenyl)prop-2-en-1-ol (3f)
Brown oil; yield: 0.76 g (72%); Rf = 0.33 (EtOAc–hexanes, 1:4).
IR (neat): 2103 (N3), 3781 cm–1 (OH).
127.1, 127.7, 128.2, 128.8, 129.6, 131.9, 135.4, 135.7, 135.9, 143.9.
MS (ES+): m/z = 356.0 [M+ + 1].
1H NMR (200 MHz, CDCl3): d = 1.86 (s, 1 H, OH), 2.36 (s, 3 H,
CH3), 4.10 (s, 2 H, CH2), 4.39 (s, 2 H, CH2), 6.65 (s, 1 H, =CH),
7.17–7.24 (m, 4 H, ArH).
Anal. Calcd for C20H21NO3S: C, 67.58; H, 5.95; N, 3.94. Found: C,
67.65; H, 5.76; N, 4.04.
13C NMR (50 MHz, CDCl3): d = 21.6, 49.3, 66.5, 127.2, 129.1,
(E)-3-(2-Fluorophenyl)-2-{[(prop-2-ynyl)tosylamino]meth-
yl}prop-2-en-1-ol (10c)
White solid; yield: 0.90 g (83%); mp 89–90 °C; Rf = 0.20 (EtOAc–
hexanes, 1:4).
129.3, 129.5, 129.6, 131.8, 133.2.
MS (ES+): m/z = 204.1 [M+ + 1].
Anal. Calcd for C11H13N3O: C, 65.01; H, 6.45; N, 20.68. Found: C,
65.30; H, 6.24; N, 20.53.
IR (KBr): 3302 (≡CH), 3403 cm–1 (OH).
1H NMR (300 MHz, CDCl3): d = 1.66 (t, J = 2.3 Hz, 1 H, ≡CH),
2.40 (s, 3 H, CH3), 2.83 (t, J = 6.8 Hz, 1 H, OH), 3.99 (t, J = 2.8 Hz,
4 H, 2 CH2), 4.36 (d, J = 5.9 Hz, 2 H, CH2), 6.72 (s, 1 H, =CH),
6.97–7.27 (m, 6 H, ArH), 7.69 (d, J = 8.3 Hz, 2 H, ArH).
13C NMR (75 MHz, CDCl3): d = 21.5, 36.1, 43.4, 64.3, 73.6, 75.9,
115.3, 115.6, 123.5, 123.7, 123.8, 124.6, 127.7, 129.1, 129.2, 129.5,
130.9, 135.4, 138.1, 143.8, 158.4, 161.7.
(E)-2-(Azidomethyl)-3-(2,4-dichlorophenyl)prop-2-en-1-ol (3g)
Brown oil; yield: 0.32 g (70%); Rf = 0.38 (EtOAc–hexanes, 1:4).
IR (neat): 2100 (N3), 3443 cm–1 (OH).
1H NMR (300 MHz, CDCl3): d = 1.81–1.85 (m, 1 H, OH), 3.97 (s,
2 H, CH2), 4.39 (d, J = 4.6 Hz, 2 H, CH2), 6.77 (s, 1 H, =CH), 7.19–
7.21 (m, 1 H, ArH), 7.27–7.29 (m, 1 H, ArH), 7.44 (d, J = 2.0 Hz, 1
H, ArH).
MS (ES+): m/z = 374.0 [M+ + 1].
13C NMR (75 MHz, CDCl3): d = 48.7, 65.1, 126.7, 127.1, 129.5,
131.2, 132.7, 134.2, 134.6, 137.9.
Anal. Calcd for C20H20FNO3S: C, 64.32; H, 5.40; N, 3.75. Found:
C, 64.68; H, 5.66; N, 3.69.
MS (ES+): m/z = 258.1 [M+ + 1].
(E)-3-(4-Chlorophenyl)-2-{[(prop-2-ynyl)tosylamino]meth-
yl}prop-2-en-1-ol (10d)
White solid; yield: 1.31 g (70%); mp 121–122 °C; Rf = 0.24
(EtOAc–hexanes, 1:4).
Anal. Calcd for C10H9Cl2N3O: C, 46.53; H, 3.51; N, 16.28. Found:
C, 46.74; H, 3.67; N, 16.01.
(E)-2-(Azidomethyl)-3-(2,6-dichlorophenyl)prop-2-en-1-ol (3h)
Brown oil; yield: 1.35 g (75%); Rf = 0.38 (EtOAc–hexanes, 1:4).
IR (neat): 2105 (N3), 3450 cm–1 (OH).
1H NMR (300 MHz, CDCl3): d = 1.96 (s, 1 H, OH), 3.81 (s, 2 H,
CH2), 4.42 (d, J = 1.1 Hz, 2 H, CH2), 6.52 (s, 1 H, =CH), 7.20 (t,
J = 8.2 Hz, 1 H, ArH), 7.35 (d, J = 7.9 Hz, 2 H, ArH).
13C NMR (50 MHz, CDCl3): d = 50.0, 64.6, 124.1, 128.4, 129.7,
134.0, 135.2, 140.1.
MS (ES+): m/z = 258.0 [M+ + 1].
IR (KBr): 3305 (≡CH), 3433 cm–1 (OH).
1H NMR (300 MHz, CDCl3): d = 1.66 (t, J = 2.3 Hz, 1 H, ≡CH),
2.42 (s, 3 H, CH3), 4.00 (d, J = 1.9 Hz, 2 H, CH2), 4.02 (s, 2 H, CH2),
4.32 (s, 2 H, CH2), 6.78 (s, 1 H, =CH), 7.09 (d, J = 8.2 Hz, 2 H,
ArH), 7.24–7.28 (m, 4 H, ArH), 7.68 (d, J = 8.2 Hz, 2 H, ArH).
13C NMR (75 MHz, CDCl3): d = 21.6, 36.4, 43.1, 64.6, 74.0, 76.1,
127.7, 128.4, 129.6, 130.2, 130.6, 133.1, 134.4, 135.3, 136.6, 144.0.
MS (ES+): m/z = 390.1 [M+ + 1].
Anal. Calcd for C20H20ClNO3S: C, 61.61; H, 5.17; N, 3.59. Found:
C, 61.85; H, 4.87; N, 3.74.
Anal. Calcd for C10H9Cl2N3O: C, 46.53; H, 3.51; N, 16.28. Found:
C, 46.35; H, 3.58; N, 16.30.
(E)-3-(4-Methylphenyl)-2-{[(prop-2-ynyl)tosylamino]meth-
yl}prop-2-en-1-ol (10f)
Off white solid; yield: 0.71 g (76%); mp 95–97 °C; Rf = 0.23
(EtOAc–hexanes, 1:4).
(E)-2-(Azidomethyl)-3-(thiophen-2-yl)prop-2-en-1-ol (3i)
Colorless oil yield: 1.50 g (86%); Rf = 0.20 (EtOAc–hexanes, 1:4).
IR (neat): 2102 (N3), 3439 cm–1 (OH).
1H NMR (300 MHz, CDCl3): d = 1.74 (s, 1 H, OH), 4.29 (s, 2 H,
CH2), 4.34 (d, J = 4.6 Hz, 2 H, CH2), 6.87 (s, 1 H, =CH), 7.05–7.07
(m, 2 H, ArH), 7.34–7.36 (m, 1 H, ArH).
13C NMR (50 MHz, CDCl3): d = 49.1, 66.3, 123.8, 126.7, 127.5,
128.9, 133.4, 138.1.
IR (KBr): 3302 (≡CH), 3452 cm–1 (OH).
1H NMR (300 MHz, CDCl3): d = 1.80 (t, J = 2.4 Hz, 1 H, ≡CH),
2.31 (s, 3 H, CH3), 2.43 (s, 3 H, CH3), 2.87 (t, J = 7.2 Hz, 1 H, OH),
4.01 (d, J = 2.3 Hz, 2 H, CH2), 4.07 (s, 2 H, CH2), 4.32 (d, J = 6.4
Hz, 2 H, CH2), 6.79 (s, 1 H, =CH), 7.04–7.10 (m, 4 H, ArH), 7.25–
7.27 (m, 2 H, ArH), 7.70 (d, J = 8.3 Hz, 2 H, ArH).
MS (ES+): m/z = 196.0 [M+ + 1].
Synthesis 2010, No. 16, 2731–2748 © Thieme Stuttgart · New York

2736
A. Mishra et al.
PAPER
13C NMR (75 MHz, CDCl3): d = 21.1, 21.5, 36.3, 43.3, 64.9, 73.9,
76.3, 127.7, 128.7, 128.9, 129.5, 129.6, 132.0, 132.8, 135.0, 135.4,
136.8, 143.8.
(E)-2-{3-Azido-2-[(prop-2-ynyloxy)methyl]prop-1-
enyl}thiophene (4i)
Brown oil; yield: 0.75 g (74%); Rf = 0.57 (EtOAc–hexanes, 1:9).
MS (ES+): m/z = 370.0 [M+ + 1].
IR (neat): 1081 (–O–), 2102 (N3), 3304 cm–1 (≡CH).
Anal. Calcd for C21H23NO3S: C, 68.27; H, 6.27; N, 3.79. Found: C,
68.15; H, 6.36; N, 3.81.
1H NMR (200 MHz, CDCl3): d = 2.47 (t, J = 2.3 Hz, 1 H, ≡CH),
4.21–4.23 (m, 6 H, 3 CH2), 6.87 (s, 1 H, =CH), 7.02–7.08 (m, 2 H,
ArH), 7.34 (dd, J1 = 4.9 Hz , J2 = 1.0 Hz, 1 H, ArH).
(E)-3-(2,4-Dichlorophenyl)-2-{[(prop-2-ynyl)tosylamino]meth-
yl}prop-2-en-1-ol (10g)
White solid; yield: 1.02 g (71%); mp 109–110 °C; Rf = 0.24
(EtOAc–hexanes, 1:4).
13C NMR (50 MHz, CDCl3): d = 49.0, 57.5, 72.8, 75.1, 77.8, 125.9,
126.9, 127.4, 129.2, 130.5, 137.9.
MS (ES+): m/z = 234.1 [M+ + 1].
IR (KBr): 3304 (≡CH), 3406 cm–1 (OH).
Anal. Calcd for C11H11N3OS: C, 56.63; H, 4.75; N, 18.01. Found:
C, 56.74; H, 4.70; N, 18.14.
1H NMR (300 MHz, CDCl3): d = 1.68 (t, J = 2.4 Hz, 1 H, ≡CH),
2.41 (s, 3 H, CH3), 2.85 (s, 1 H, OH), 3.91 (s, 2 H, CH2), 4.00 (d,
J = 2.3 Hz, 2 H, CH2), 4.37 (s, 2 H, CH2), 6.72 (s, 1 H, =CH), 7.05
(d, J = 8.3 Hz, 1 H, ArH), 7.16 (dd, J1 = 8.2 Hz , J2 = 2.0 Hz, 1 H,
ArH), 7.26–7.28 (m, 2 H, ArH), 7.37 (d, J = 2.0 Hz, 1 H, ArH), 7.69
(d, J = 8.3 Hz, 2 H, ArH).
13C NMR (75 MHz, CDCl3): d = 21.6, 36.0, 42.8, 64.1, 73.7, 75.7,
126.7, 127.7, 128.0, 129.1, 129.6, 131.6, 133.0, 133.8, 134.6, 135.3,
137.9, 144.0.
(E)-7-Benzylidene-7,8-dihydro-4H,6H-[1,2,3]triazolo[5,1-
c][1,4]oxazepine [(E)-5a] and (Z)-7-Benzylidene-7,8-dihydro-
4H,6H-[1,2,3]triazolo[5,1-c][1,4]oxazepine [(Z)-5a]; Typical
Procedure for 5a–i, 13a,c,d,f,g
Compound 4a (1.20 g, 5.29 mmol) was dissolved in anhyd toluene
and heated at reflux for 7 h. Then the mixture was cooled to r.t. and
solvent was evaporated to obtain a residue, which was purified by
column chromatography (silica gel, 230–400 mesh) to furnish pure
(E)-5a (EtOAc–CHCl3, 3:97) (0.60 g, 50%) and (Z)-5a (EtOAc–
CHCl3, 3:97) (0.45 g, 38%).
MS (ES+): m/z = 424.1 [M+ + 1].
Anal. Calcd for C20H19Cl2NO3S: C, 56.61; H, 4.51; N, 3.30. Found:
C, 56.95; H, 4.32; N, 3.36.
(E)-5a
White solid; mp 103–104 °C; Rf = 0.24 (EtOAc–CHCl3, 3:97).
IR (KBr): 1090 cm–1 (–O–).
1H NMR (300 MHz, CDCl3): d = 4.57 (s, 2 H, CH2), 4.85 (s, 2 H,
CH2), 5.29 (s, 2 H, CH2), 6.86 (s, 1 H, =CH), 7.20 (s, 1 H, ArH),
7.23 (d, J = 1.4 Hz, 1 H, ArH), 7.32–7.42 (m, 3 H, ArH), 7.54 (s, 1
H, ArH).
13C NMR (75 MHz, CDCl3): d = 49.5, 62.1, 78.9, 128.6, 129.0,
129.1, 130.6, 132.0, 134.8, 135.4, 136.0.
MS (ES+): m/z = 228.1 [M+ + 1].
(E)-1-{3-Azido-2-[(prop-2-ynyloxy)methyl]prop-1-enyl}-4-
chlorobenzene (4d); Typical Procedure for 4a–i
To a stirred soln of 3d (0.50 g, 2.24 mmol) in anhyd THF (10 mL)
was added NaH (0.09 g, 3.36 mmol, 60% in oil). After 10 min, 80%
propargyl bromide in toluene (0.32 mL, 2.69 mmol) was added and
the mixture was stirred at r.t. for 2 h. When the reaction was com-
plete, the solvent was removed and the residue was diluted with
EtOAc (20 mL) and H2O (20 mL). The aqueous layer was separated
and extracted with EtOAc (3 × 10 mL). The combined organic lay-
ers were dried (anhyd Na2SO4) and concentrated to obtain the crude
product, which was purified by column chromatography (silica gel,
100–200 mesh, EtOAc–hexanes, 3:97) yielded pure 4d (0.41 g,
70%) as a colorless oil; Rf = 0.73 (EtOAc–hexanes, 1:9).
Anal. Calcd for C13H13N3O2: C, 68.70; H, 5.77; N, 18.49. Found: C,
68.87; H, 5.85; N, 18.37.
IR (neat): 1086 (–O–), 2099 (N3), 3299 cm–1 (≡CH).
(Z)-5a
White solid; mp 105–106 °C; Rf = 0.24 (EtOAc–CHCl3, 3:97).
IR (KBr): 1099 cm–1 (–O–).
1H NMR (300 MHz, CDCl3): d = 4.69 (s, 2 H, CH2), 4.77 (s, 2 H,
CH2), 5.26 (s, 2 H, CH2), 6.93 (s, 1 H, =CH), 7.17 (d, J = 7.2 Hz, 2
H, ArH), 7.31 (s, 1 H ArH), 7.37 (d, J = 7.4 Hz, 2 H, ArH), 7.47 (s,
1 H, ArH).
13C NMR (75 MHz, CDCl3): d = 55.4, 63.1, 71.7, 128.2, 128.5,
129.0, 131.1, 131.9, 134.8, 134.9, 135.1.
MS (ES+): m/z = 228.1 [M+ + 1].
1H NMR (300 MHz, CDCl3): d = 2.45 (s, 1 H, ≡CH), 3.99 (s, 2 H,
CH2), 4.23 (d, J = 1.8 Hz, 4 H, CH2), 6.76 (s, 1 H, =CH), 7.19 (d,
J = 8.4 Hz, 2 H, ArH), 7.33 (d, J = 8.4 Hz, 2 H, ArH).
13C NMR (50 MHz, CDCl3): d = 48.8, 55.7, 72.6, 75.5, 96.6, 128.9,
129.1, 129.4, 130.5, 130.8, 132.2, 133.9.
MS (ES+): m/z = 262.1 [M+ + 1].
Anal. Calcd for C13H12ClN3O: C, 59.66; H, 4.62; N, 16.06. Found:
C, 59.72 H, 4.54; N, 16.18.
(E)-1-{3-Azido-2-[(prop-2-ynyloxy)methyl]prop-1-enyl}-2-fluo-
robenzene (4c)
Orange oil; yield: 0.30 g (83%); Rf = 0.65 (EtOAc–hexanes, 1:9).
Anal. Calcd for C13H13N3O: C, 68.70; H, 5.77; N, 18.49. Found: C,
68.89; H, 5.89; N, 18.41.
IR (neat): 1087 (–O–), 2102 (N3), 3306 cm-1 (≡CH).
1H NMR (300 MHz, CDCl3): d = 2.45 (t, J = 2.3 Hz, 1 H, ≡CH),
3.98 (s, 2 H, CH2), 4.24 (d, J = 2.3 Hz, 2 H, CH2), 4.28 (d, J = 0.8
Hz, 2 H, CH2), 6.77 (s, 1 H, =CH), 7.24–7.32 (m, 4 H, ArH).
13C NMR: not recorded due to the unstable nature of compound.
MS (ES+): m/z = 246.1 [M+ + 1].
(E)-7-(2-Chlorobenzylidene)-7,8-dihydro-4H,6H-[1,2,3]triazo-
lo[5,1-c][1,4]oxazepine [(E)-5b]
White solid; yield: 0.17 g (49%); mp 127–128 °C; Rf = 0.24
(EtOAc–CHCl3, 3:97).
IR (KBr): 1046 cm–1 (–O–).
1H NMR (200 MHz, CDCl3): d = 4.57 (d, J = 1.1 Hz, 2 H, CH2),
4.85 (s, 2 H, CH2), 5.30 (s, 2 H, CH2), 6.86 (s, 1 H, =CH), 7.20–7.24
(m, 1 H, ArH), 7.28–7.45 (m, 3 H, ArH), 7.55 (s, 1 H, ArH).
13C NMR (75 MHz, CDCl3): d = 49.3, 61.9, 78.7, 128.4, 128.8,
128.9, 130.4, 131.8, 134.6, 135.3, 135.8.
Anal. Calcd for C13H12FN3O: C, 63.66; H, 4.93; N, 17.13. Found:
C, 63.74; H, 4.82; N, 17.25.
Synthesis 2010, No. 16, 2731–2748 © Thieme Stuttgart · New York

PAPER
Fused Triazoles and Tetrazoles via Intramolecular Cycloaddition
2737
MS (ES+): m/z = 262.1 [M+ + 1].
HRMS (EI): m/z [M]+ calcd for C13H12ClN3O: 261.0669; found:
261.0669.
DART-HRMS (ESI+): m/z [M + H]+ calcd for C13H13ClN3O:
262.07471; found: 262.07288.
(E)-7-(4-Fluorobenzylidene)-7,8-dihydro-4H,6H-[1,2,3]triazo-
lo[5,1-c][1,4]oxazepine [(E)-5e]
White solid; yield: 0.10 g (50%); mp 98–99 °C; Rf = 0.23 (EtOAc–
CHCl3, 3:97).
IR (KBr): 1084 cm–1 (–O–).
(Z)-7-(2-Chlorobenzylidene)-7,8-dihydro-4H,6H-[1,2,3]triazo-
lo[5,1-c][1,4]oxazepine [(Z)-5b]
White solid; yield: 0.15 g (43%); mp 98–99 °C; Rf = 0.24 (EtOAc–
CHCl3, 3:97).
IR (KBr): 1046 (–O–) cm–1.
1H NMR (300 MHz, CDCl3): d = 4.56 (s, 2 H, CH2), 4.85 (d, J = 1.4
Hz, 2 H, CH2), 5.27 (d, J = 1.5 Hz, 2 H, CH2), 6.80 (s, 1 H, =CH),
7.06–7.12 (m, 2 H, ArH), 7.20 (d, J = 1.9 Hz, 2 H, ArH), 7.54 (s, 1
H, ArH).
13C NMR (75 MHz, CDCl3): d = 49.5, 62.2, 78.9, 116.1, 116.4,
130.8, 130.9, 131.0, 132.2, 134.3, 136.1, 161.2, 164.5.
1H NMR (200 MHz, CDCl3): d = 4.69 (d, 2 H, CH2), 4.77 (s, 2 H,
CH2), 5.26 (s, 2 H, CH2), 6.93 (s, 1 H, =CH), 7.17 (d, J = 6.5 Hz, 2
H ArH), 7.36 (d, J = 6.3 Hz, 2 H ArH), 7.48 (s, 1 H, ArH).
13C NMR (75 MHz, CDCl3): d = 55.5, 63.2, 71.8, 128.3, 128.6,
129.1, 131.2, 132.0, 134.9, 135.2.
MS (ES+): m/z = 246.1 [M+ + 1].
MS (ES+): m/z = 262.1 [M+ + 1].
Anal. Calcd for C13H12FN3O: C, 63.66; H, 4.93; N, 17.13. Found:
C, 63.71; H, 4.83; N, 17.07.
DART-HRMS (ESI+): m/z [M + H]+ calcd for C13H13ClN3O:
262.07471; found: 262.07288.
(Z)-7-(4-Fluorobenzylidene)-7,8-dihydro-4H,6H-[1,2,3]triazo-
lo[5,1-c][1,4]oxazepine [(Z)-5e]
White solid; yield: 0.08 g (40%); mp 100–101 °C; Rf = 0.23
(EtOAc–CHCl3, 3:97).
IR (KBr): 1046 cm–1 (–O–).
1H NMR (300 MHz, CDCl3): d = 4.65 (d, J = 1.1 Hz, 2 H, CH2),
4.78 (s, 2 H, CH2), 5.25 (s, 2 H, CH2), 6.88 (s, 1 H, =CH), 7.06 (t,
J = 8.7 Hz, 2 H, ArH), 7.13–7.18 (m, 2 H, ArH), 7.48 (s, 1 H, ArH).
13C NMR (75 MHz, CDCl3): d = 55.4, 63.1, 71.6, 115.4, 115.7,
130.7, 130.8, 130.89, 130.94, 131.2, 131.8, 133.9, 134.8, 160.8,
164.1.
(E/Z)-7-(2-Fluorobenzylidene)-7,8-dihydro-4H,6H-[1,2,3]tria-
zolo[5,1-c][1,4]oxazepine [(E/Z)-5c]
White solid; yield: 0.20 g (80%); ratio of diastereomers 2:1; mp
137–138 °C; Rf = 0.22 (EtOAc–CHCl3, 3:97).
IR (KBr): 1097 cm–1 (–O–).
1H NMR (200 MHz, CDCl3): d = 4.56 (s, 2 H, CH2), 4.60 (d, J = 1.0
Hz, 2 H, CH2), 4.77 (s, 2 H, CH2), 4.86 (s, 2 H, CH2), 5.25 (s, 2 H,
CH2), 5.28 (s, 2 H, CH2), 6.86 (s, 1 H, =CH), 6.90 (s, 1 H, =CH),
7.04 (s, 1 H, ArH), 7.08 (s, 1 H, ArH), 7.13–7.20 (m, 3 H, ArH),
7.28–7.36 (m, 3 H, ArH), 7.48 (s, 1 H, =CH), 7.53 (s, 1 H, ArH).
13C NMR (50 MHz, CDCl3): d = 49.4, 55.3, 62.1, 63.1, 72.0, 76.8,
78.3, 127.8, 127.9, 128.0, 130.3, 130.4, 130.5, 130.6, 130.7, 131.3,
131.7, 131.8, 132.7, 135.7.
MS (ES+): m/z = 246.1 [M+ + 1].
Anal. Calcd for C13H12FN3O: C, 63.66; H, 4.93; N, 17.13. Found:
C, 63.69; H, 4.87; N, 17.10.
MS (ES+): m/z = 246.2 [M+ + 1].
HRMS (EI): m/z [M]+ calcd for C13H12FN3O: 245.0964; found:
245.0993.
(E)-7-(4-Methylbenzylidene)-7,8-dihydro-4H,6H-[1,2,3]triazo-
lo[5,1-c][1,4]oxazepine [(E)-5f]
White solid; yield: 0.13 g (52%); mp 106–107 °C; Rf = 0.23
(EtOAc–CHCl3, 3:97).
IR (KBr): 1010 cm–1 (–O–).
(E)-7-(4-Chlorobenzylidene)-7,8-dihydro-4H,6H-[1,2,3]triazo-
lo[5,1-c][1,4]oxazepine [(E)-5d]
White solid; yield: 0.18 g (50%); mp 118–119 °C; Rf = 0.23
(EtOAc–CHCl3, 3:97).
IR (KBr): 1048 cm–1 (–O–) .
1H NMR (300 MHz, CDCl3): d = 4.57 (s, 2 H, CH2), 4.87 (s, 2 H,
CH2), 5.28 (s, 2 H, CH2), 6.81 (s, 1 H, =CH), 7.17 (d, J = 8.4 Hz, 2
H ArH), 7.37–7.40 (m, 2 H, ArH), 7.56 (s, 1 H, ArH).
1H NMR (300 MHz, CDCl3): d = 2.36 (s, 3 H, CH3), 4.55 (s, 2 H,
CH2), 4.84 (s, 2 H, CH2), 5.29 (s, 2 H, CH2), 6.82 (s, 1 H, =CH), 7.11
(d, J = 7.6 Hz, 2 H, ArH), 7.20 (d, J = 7.4 Hz, 2 H, ArH), 7.53 (s, 1
H, ArH).
13C NMR (75 MHz, CDCl3): d = 21.6, 49.7, 62.0, 79.0, 129.0,
129.85, 129.90, 132.0, 132.1, 135.6, 136.1, 138.7.
13C NMR (75 MHz, CDCl3): d = 49.2, 62.0, 78.6, 129.2, 130.2,
131.2, 131.9, 133.0, 133.9, 134.5, 135.8.
MS (ES+): m/z = 242.0 [M+ + 1].
MS (ES+): m/z = 262.1 [M+ + 1].
DART-HRMS (ESI+): m/z [M + H]+ calcd for C14H16N3O:
242.1934; found: 242.12781.
HRMS (EI): m/z [M]+ calcd for C13H12ClN3O: 261.0669; found:
261.0669.
(Z)-7-(4-Methylbenzylidene)-7,8-dihydro-4H,6H-[1,2,3]triazo-
lo[5,1-c][1,4]oxazepine [(Z)-5f]
White solid; yield: 0.10 g (40%); mp 106–107 °C; Rf = 0.23
(EtOAc–CHCl3, 3:97).
IR (KBr): 1100 cm–1 (–O–).
(Z)-7-(4-Chlorobenzylidene)-7,8-dihydro-4H,6H-[1,2,3]triazo-
lo[5,1-c][1,4]oxazepine [(Z)-5d]
White solid; yield: 0.16 g (46%); mp 89–90 °C; Rf = 0.23 (EtOAc–
CHCl3, 3:97).
IR (KBr): 1048 cm–1 (–O–).
1H NMR (300 MHz, CDCl3): d = 2.36 (s, 3 H, CH3), 4.69 (s, 2 H,
CH2), 4.76 (s, 2 H, CH2), 5.24 (s, 2 H, CH2), 6.89 (s, 1 H, =CH), 7.07
(s, 2 H, ArH), 7.18 (d, J = 5.3 Hz, 2 H, ArH), 7.46 (s, 1 H, ArH).
13C NMR (75 MHz, CDCl3): d = 21.6, 55.8, 63.5, 72.1, 129.3,
129.6, 131.5, 132.4, 135.2, 135.5, 138.6.
1H NMR (300 MHz, CDCl3): d = 4.64 (s, 2 H, CH2), 4.78 (s, 2 H,
CH2), 5.25 (s, 2 H, CH2), 6.87 (s, 1 H, =CH), 7.11 (d, J = 7.7 Hz, 2
H, ArH), 7.35 (d, J = 8.4 Hz, 2 H, ArH), 7.48 (s, 1 H, ArH).
13C NMR (75 MHz, CDCl3): d = 55.5, 63.3, 71.7, 128.8, 130.3,
131.3, 132.8, 133.4, 133.8, 134.3, 134.8.
MS (ES+): m/z = 242.0 [M+ + 1].
MS (ES+): m/z = 262.1 [M+ + 1].
Synthesis 2010, No. 16, 2731–2748 © Thieme Stuttgart · New York

2738
A. Mishra et al.
PAPER
Anal. Calcd for C14H15N3O: C, 69.69; H, 6.27; N, 17.41. Found: C,
69.87; H, 6.38; N, 17.25.
MS (ES+): m/z = 381.1 [M+ + 1].
Anal. Calcd for C20H20N4O2S: C, 63.14; H, 5.30; N, 14.73. Found:
C, 63.21; H, 5.27; N, 14.73.
(E)-7-(2,4-Dichlorobenzylidene)-7,8-dihydro-4H,6H-[1,2,3]tri-
azolo[5,1-c][1,4]oxazepine [(E)-5g]
White solid; yield: 0.05 g (71%); mp 98–99 °C; Rf = 0.24 (EtOAc–
CHCl3, 3:97).
IR (KBr): 1010 cm–1 (–O–).
(Z)-7-Benzylidene-5-tosyl-5,6,7,8-tetrahydro-4H-[1,2,3]triazo-
lo[1,5-a][1,4]diazepine [(Z)-13a]
White solid; yield: 0.16 g (40%); mp 162–163 °C; Rf = 0.23
(EtOAc–CHCl3, 3:97).
1H NMR (300 MHz, CDCl3): d = 4.63 (s, 2 H, CH2), 4.89 (s, 2 H,
CH2), 5.20 (s, 2 H, CH2), 6.86 (s, 1 H, =CH), 7.08 (d, J = 8.3 Hz, 1
H, ArH), 7.33 (d, J = 8.4 Hz, 1 H, ArH), 7.46 (s, 1 H, ArH), 7.59 (s,
1 H, ArH).
1H NMR (300 MHz, CDCl3): d = 2.41 (s, 3 H, CH3), 4.37 (s, 2 H,
CH2), 4.53 (s, 2 H, CH2), 5.00 (s, 2 H, CH2), 6.92 (s, 1 H, =CH), 7.17
(d, J = 7.4 Hz, 2 H, ArH), 7.33–7.40 (m, 4 H, ArH), 7.50 (s, 1 H,
ArH), 7.55 (d, J = 7.4 Hz, 3 H, ArH).
13C NMR (75 MHz, CDCl3): d = 49.2, 62.1, 78.0, 127.6, 129.6,
13C NMR (75 MHz, CDCl3): d = 21.6, 41.5, 49.9, 55.3, 127.1,
128.5, 128.6, 128.8, 128.9, 129.8, 130.0, 131.6, 132.4, 134.4, 136.8,
144.3.
131.1, 131.3, 131.9, 132.7, 134.4, 135.1, 135.6.
MS (ES+): m/z = 296.1 [M+ + 1].
MS (ES+): m/z = 381.1 [M+ + 1].
Anal. Calcd for C13H11Cl2N3O: C, 52.72; H, 3.74; N, 14.19. Found:
C, 52.32; H, 4.04; N, 14.49.
Anal. Calcd for C20H20N4O2S: C, 63.14; H, 5.30; N, 14.73. Found:
C, 63.21; H, 5.27; N, 14.73.
(E)-7-[2,6-Dichlorobenzylidene]-7,8-dihydro-4H,6H-[1,2,3]tri-
azolo[5,1-c][1,4]oxazepine [(E)-5h]
White solid; yield: 0.65 g (81%); mp 110–112 °C; Rf = 0.21
(E/Z)-7-(2-Fluorobenzylidene)-5-tosyl-5,6,7,8-tetrahydro-4H-
[1,2,3]triazolo[1,5-a][1,4]diazepine [(E/Z)-13c]
(EtOAc–CHCl3, 3:97).
IR (KBr): 1095 cm–1 (–O–).
1H NMR (300 MHz, CDCl3): d = 4.68 (d, J = 1.0 Hz, 2 H, CH2),
4.88 (s, 2 H, CH2), 5.00 (s, 2 H, CH2), 6.64 (s, 1 H, =CH), 7.22–7.25
(m, 1 H, ArH), 7.35–7.37 (m, 2 H, ArH), 7.48 (s, 1 H, ArH).
13C NMR (75 MHz, CDCl3): d = 49.3, 61.9, 77.8, 128.3, 129.4,
130.1, 131.3, 132.4, 134.7, 135.0, 135.5.
MS (ES+): m/z = 296.1 [M+ + 1].
DART-HRMS (ESI+): m/z [M + H]+ calcd for C13H12Cl2N3O:
White solid; yield: 0.51 g (85%); ratio of diastereomers 10:1; mp
150–152 °C; Rf = 0.24 (EtOAc–CHCl3, 3:97).
1H NMR (300 MHz, CDCl3): d = 2.34 (s, 3 H, CH3), 2.43 (s, 3 H,
CH3), 4.27 (s, 2 H, CH2), 4.36 (s, 2 H, CH2), 4.57 (s, 2 H, CH2), 4.74
(s, 2 H, CH2), 5.01 (d, J = 8.3 Hz, 4 H, 2 CH2), 6.88 (s, 2 H, 2 =CH),
7.07–7.20 (m, 14 H, ArH), 7.32–7.36 (m, 4 H, ArH).
13C NMR (75 MHz, CDCl3): d = 21.5, 22.7, 41.4, 50.1, 50.2, 55.0,
115.7, 116.0, 122.0, 122.2, 124.20, 124.24, 126.9, 127.1, 129.58,
129.61, 129.8, 130.0, 130.5, 130.6, 130.8, 131.6, 132.6, 135.3,
144.3, 158.0, 161.3.
MS (ES+): m/z = 399.2 [M+ + 1].
296.0357; found: 296.0323.
Anal. Calcd for C20H19FN4O2S: C, 60.29; H, 4.81; N, 14.06. Found:
C, 60.34; H, 4.72; N, 14.17.
(E/Z)-7-(2-Thiophenylidene)-7,8-dihydro-4H,6H-[1,2,3]triazo-
lo[5,1-c][1,4]oxazepine [(E/Z)-5i]
Brown oil ; yield: 0.21 g (78%); ratio of diastereomers 3:2; Rf = 0.24
(EtOAc–CHCl3, 3:97).
IR (neat): 1102 cm–1 (–O–).
(E)-7-(4-Chlorobenzylidene)-5-tosyl-5,6,7,8-tetrahydro-4H-
[1,2,3]triazolo[1,5-a][1,4]diazepine [(E)-13d]
White solid; yield: 0.43 g (54%); mp 184–186 °C; Rf = 0.25
(EtOAc–CHCl3, 3:97).
1H NMR (300 MHz, CDCl3): d = 2.32 (s, 3 H, CH3), 4.30 (s, 2 H,
CH2), 4.71 (s, 2 H, CH2), 4.96 (s, 2 H, CH2), 6.70 (s, 1 H, =CH), 6.97
(d, J = 7.7 Hz, 2 H, ArH), 7.16 (d, J = 7.0 Hz, 2 H, ArH), 7.26–7.34
(m, 2 H, ArH), 7.51 (t, J = 7.9 Hz, 2 H, ArH), 7.57 (s, 1 H, ArH).
13C NMR (75 MHz, CDCl3): d = 21.4, 41.2, 49.4, 57.2, 127.1,
129.0, 129.8, 130.0, 132.5, 133.3, 134.5, 135.2, 135.7, 144.2.
MS (ES+): m/z = 415.1 [M+ + 1].
1H NMR (300 MHz, CDCl3): d = 4.52 (d, J = 0.8 Hz, 2 H, CH2),
4.81 (s, 4 H, 2 CH2), 4.86 (s, 2 H, CH2), 5.25 (s, 2 H, CH2), 5.46 (s,
2 H, CH2), 6.85 (s, 1 H, =CH), 6.95 (s, 1 H, =CH), 7.00 (d, J = 3.3
Hz, 1 H, ArH), 7.04–7.07 (m, 2 H, ArH), 7.14 (d, J = 3.5 Hz, 1 H,
ArH), 7.36–7.39 (m, 2 H, ArH), 7.44 (s, 1 H, ArH), 7.49 (s, 1 H,
ArH).
13C NMR (50 MHz, CDCl3): d = 49.3, 55.0, 61.5, 64.2, 72.1, 76.5,
78.3, 125.9, 127.3, 127.6, 127.7, 129.5, 129.6, 130.7, 131.5, 134.3,
135.5, 137.0, 137.6.
Anal. Calcd for C20H19ClN4O2S: C, 57.90; H, 4.62; N, 13.50.
Found: C, 57.86; H, 4.73; N, 13.45.
MS (ES+): m/z = 234.0 [M+ + 1].
DART-HRMS (ESI+): m/z [M]+ calcd for C11H12N3OS: 234.0701;
found: 234.0675.
(Z)-7-(4-Chlorobenzylidene)-5-tosyl-5,6,7,8-tetrahydro-4H-
[1,2,3]triazolo[1,5-a][1,4]diazepine [(Z)-13d]
White solid; yield: 0.32 g (40%); mp 185–186 °C; Rf = 0.23
(EtOAc–CHCl3, 3:97).
1H NMR (300 MHz, CDCl3): d = 2.42 (s, 3 H, CH3), 4.30 (s, 2 H,
CH2), 4.53 (s, 2 H, CH2), 5.02 (s, 2 H, CH2), 6.86 (s, 1 H, =CH), 7.11
(d, J = 8.1 Hz, 2 H, ArH), 7.26–7.36 (m, 4 H, ArH), 7.50 (s, 1 H,
ArH), 7.56 (d, J = 8.0 Hz, 2 H, ArH).
(E)-7-Benzylidene-5-tosyl-5,6,7,8-tetrahydro-4H-[1,2,3]triazo-
lo[1,5-a][1,4]diazepine [(E)-13a]
White solid; yield: 0.22 g (55%); mp 164–165 °C; Rf = 0.27
(EtOAc–CHCl3, 3:97).
1H NMR (300 MHz, CDCl3): d = 2.31 (s, 3 H, CH3), 4.31 (s, 2 H,
CH2), 4.72 (s, 2 H, CH2), 4.99 (s, 2 H, CH2), 6.76 (s, 1 H, =CH),
7.02–7.04 (m, 2 H, ArH), 7.16 (d, J = 8.1 Hz, 2 H, ArH), 7.30–7.38
(m, 4 H, ArH), 7.51 (d, J = 8.3 Hz, 1 H, ArH), 7.56 (s, 1 H, ArH).
13C NMR (75 MHz, CDCl3): d = 21.4, 41.1, 49.5, 57.3, 126.4,
127.1, 128.5, 128.6, 128.8, 128.9, 129.8, 132.4, 133.4, 134.2, 135.7,
136.6, 144.2.
13C NMR (75 MHz, CDCl3): d = 21.5, 41.6, 49.8, 55.3, 127.0,
128.8, 129.1, 130.0, 130.2, 131.7, 132.3, 132.8, 134.4, 135.1, 135.2,
144.4.
MS (ES+): m/z = 415.1 [M+ + 1].
Synthesis 2010, No. 16, 2731–2748 © Thieme Stuttgart · New York

PAPER
Fused Triazoles and Tetrazoles via Intramolecular Cycloaddition
2739
Anal. Calcd for C20H19ClN4O2S: C, 57.90; H, 4.62; N, 13.50.
Found: C, 57.86; H, 4.73; N, 13.45.
7-(4-Methylbenzyl)-4H,6H-[1,2,3]triazolo[5,1-c][1,4]oxazepine
(7f); Typical Procedure for 7a,f, 14g, 15g, 25g, 26g
To a stirred soln of (E/Z)-5f (0.10 g, 0.41 mmol) in anhyd THF (5
mL) was added DBU (0.09 mL, 0.62 mmol) and the mixture was
heated at 80 °C in an oil bath. (E)-5f was consumed to give product
within 2 h, (Z)-5f was unreacted. The reaction was continued for 24
h (TLC monitoring). THF was evaporated under vacuum and the
residue was extracted with EtOAc (3 × 20 mL). The combined or-
ganic layers were washed with brine (30 mL), dried (anhyd
Na2SO4), and concentrated to give crude product. Purification by
column chromatography (silica gel, 100–200 mesh, EtOAc–hex-
anes, 2:3) afforded 7f (0.049 g, 49%) as a white solid and also (Z)-
5f (0.047 g, 48%) as a white solid; mp 95–98 °C; Rf = 0.26 (EtOAc–
hexanes, 2:3).
(E/Z)-7-(4-Methylbenzylidene)-5-tosyl-5,6,7,8-tetrahydro-4H-
[1,2,3]triazolo[1,5-a][1,4]diazepine [(E/Z)-13f]
Colorless oil; yield: 0.66 g (83%); ratio of diastereomers 1:1;
Rf = 0.24 (EtOAc–CHCl3, 3:97).
1H NMR (300 MHz, CDCl3): d = 2.36 (s, 6 H, 2 CH3), 2.38 (s, 6 H,
2 CH3), 4.31 (s, 4 H, 2 CH2), 4.39 (s, 2 H, CH2), 4.53 (s, 2 H, CH2),
4.72 (s, 4 H, 2 CH2), 6.69 (s, 1 H, =CH), 6.75 (s, 1 H, =CH), 6.90–
6.96 (m, 4 H, ArH), 7.09 (d, J = 7.9 Hz, 4 H, ArH), 7.16–7.28 (m, 4
H, ArH), 7.51–7.59 (m, 6 H, ArH).
13C NMR (50 MHz, CDCl3): d = 21.8, 22.0, 30.1, 41.8, 41.9, 50.5,
50.7, 55.4, 55.5, 124.6, 127.39, 127.40, 127.6, 130.1, 130.4, 130.9,
131.0, 131.2, 132.1, 133.1, 135.6, 144.7.
IR (KBr): 1031 cm–1 (–O–).
1H NMR (200 MHz, CDCl3): d = 2.34 (s, 3 H, CH3), 3.37 (s, 2 H,
CH2), 4.43 (s, 2 H, CH2), 4.79 (s, 2 H, CH2), 7.13 (s, 4 H, =CH,
ArH), 7.34 (s, 1 H, ArH), 7.48 (s, 1 H, ArH).
13C NMR (50 MHz, CDCl3): d = 21.5, 39.4, 63.7, 74.8, 117.9,
121.8, 129.0, 130.0, 130.9, 131.6, 134.4, 136.6, 137.2, 156.7.
MS (ES+): m/z = 395.3 [M+ + 1].
Anal. Calcd for C21H22N4O2S: C, 63.94; H, 5.62; N, 14.20. Found:
C, 64.12, H, 5.53; N, 14.31.
(E)-7-(2,4-Dichlorobenzylidene)-5-tosyl-5,6,7,8-tetrahydro-4H-
[1,2,3]triazolo[1,5-a][1,4]diazepine [(E)-13g]
White solid; yield: 0.25 g (83%); mp 150–152 °C; Rf = 0.30
(EtOAc–CHCl3, 3:97).
1H NMR (300 MHz, CDCl3): d = 2.42 (s, 3 H, CH3), 4.15 (s, 2 H,
CH2), 4.55 (s, 2 H, CH2), 5.03 (s, 2 H, CH2), 6.90 (s, 1 H, =CH), 7.15
(d, J = 8.3 Hz, 1 H, ArH), 7.25–7.30 (m, 4 H, ArH), 7.43 (d, J = 2.0
Hz, 1 H, ArH), 7.52–7.54 (m, 2 H, ArH).
MS (ES+): m/z = 242.0 [M+ + 1].
Anal. Calcd for C14H15N3O: C, 69.69; H, 6.27; N, 17.41. Found: C,
69.35; H, 6.43; N, 17.15.
7-Benzyl-4H,6H-[1,2,3]triazolo[5,1-c][1,4]oxazepine (7a)
White solid; yield: 0.047 g (47%); mp 90–92 oC; Rf = 0.23 (EtOAc–
hexanes, 2:3).
13C NMR (75 MHz, CDCl3): d = 21.6, 41.4, 49.9, 55.0, 127.0,
127.2, 129.6, 130.1, 130.7, 131.3, 132.0, 132.4, 132.8, 134.3, 134.9,
135.2, 144.5.
IR (KBr): 1083 cm–1 (–O–).
1H NMR (200 MHz, CDCl3): d = 3.39 (s, 2 H, CH2), 4.46 (s, 2 H,
CH2), 4.81 (s, 2 H, CH2), 7.16–7.18 (m, 5 H, CH and ArH), 7.35 (s,
1 H, ArH), 7.50 (s, 1 H, =CH).
MS (ES+): m/z = 449.2 [M+ + 1].
Anal. Calcd for C20H18Cl2N4O2S: C, 53.46; H, 4.04; N, 12.47.
Found: C, 53.15; H, 4.32; N, 12.55.
13C NMR (CDCl3, 50 MHz): d = 39.9, 63.5, 73.9, 120.5, 129.0,
130.0, 130.9, 131.6, 133.4, 136.4, 137.3.
MS (ES+): m/z = 228.1 [M+ + 1].
7-Benzyl-7,8-dihydro-4H,6H-[1,2,3]triazolo[5,1-c][1,4]ox-
azepine (6a)
Anal. Calcd for C13H13N3O: C, 68.70; H, 5.77; N, 18.49. Found: C,
68.88; H, 5.89; N, 18.40.
To a soln of diastereomeric mixture of 5a (0.10 g, 0.44 mmol) in
MeOH was added 10% Pd/C (0.01 g) under N2. Thereafter, the at-
mosphere of the vessel was replaced by H2 gas and reaction was car-
ried out on the Parr assembly at 24 mbar at r.t. for 2 h. The catalyst
was then filtered through Celite and the filtrate was evaporated on a
rotavapor under reduced pressure to yield a residue that was puri-
fied by recrystallization or column chromatography (silica gel,
EtOAc–hexanes, 1:1), to give pure 6a (0.09 g, 89%) as white solid;
mp 113–115 °C; Rf = 0.31 (EtOAc–hexanes, 1:1).
(Z)-7-(2,4-Dichlorobenzylidene)-5-tosyl-5,8-dihydro-4H-
[1,2,3]triazolo[1,5-a][1,4]diazepine (14g)
White solid; yield: 0.048 g (48%); mp 153–154 °C; Rf = 0.30
(EtOAc–hexanes, 1:1).
1H NMR (300 MHz, CDCl3): d = 2.36 (s, 3 H, CH3), 3.46 (s, 2 H,
CH2), 4.25 (s, 2 H, CH2), 4.72 (s, 2 H, CH2), 6.87 (s, 1 H, =CH),
7.07–7.15 (m, 3 H, ArH), 7.22–7.28 (m, 3 H, ArH), 7.44 (d, J = 2.0
Hz, 1 H, ArH), 7.49 (s, 1 H, ArH).
13C NMR (75 MHz, CDCl3): d = 21.5, 37.3, 42.3, 51.9, 122.8,
124.9, 126.7, 127.7, 129.6, 130.0, 131.9, 132.0.
MS (ES+): m/z = 449.2 [M+ + 1].
IR (KBr): 1090 cm–1 (–O–).
1H NMR (300 MHz, CDCl3): d = 2.22–2.26 (m, 1 H, CH), 2.45–
2.60 (m, 2 H, CH2), 3.93 (dd, J1 = 12.7 Hz, J2 = 5.9 Hz, 1 H, CH2),
4.03 (dd, J1 = 12.7 Hz, J2 = 2.4 Hz, 1 H, CH2), 4.56 (dd, J1 = 14.3
Hz, J2 = 6.6 Hz, 1 H, CH2), 4.63 (d, J = 1.8 Hz, 1 H, CH2), 4.68 (s,
1 H, CH2), 4.80 (d, J = 14.7 Hz, 1 H, CH2), 7.14–7.17 (m, 2 H,
ArH), 7.21–7.27 (m, 1 H, ArH), 7.29–7.34 (m, 2 H, ArH), 7.58 (s,
1 H, ArH).
13C NMR (75 MHz, CDCl3): d = 35.1, 40.3, 53.7, 63.0, 77.8, 127.0,
129.0, 129.4, 133.0, 136.6, 138.5.
MS (ES+): m/z = 230.2 [M+ + 1].
Anal. Calcd for C20H18Cl2N4O2S: C, 53.46; H, 4.04; N, 12.47.
Found: C, 53.15; H, 4.32; N, 12.55.
(Z)-7-(2,4-Dichlorobenzylidene)-5-tosyl-5,6-dihydro-4H-
[1,2,3]triazolo[1,5-a][1,4]diazepine (15g)
White solid; yield: 0.046 g (46%); mp 150–152 °C; Rf = 0.29
(EtOAc–hexanes, 1:1).
1H NMR (300 MHz, CDCl3): d = 2.40 (s, 3 H, CH3), 3.54 (s, 2 H,
CH2), 4.86 (s, 2 H, CH2), 4.97 (s, 2 H, CH2), 6.64 (s, 1 H, =CH), 7.09
(d, J = 8.3 Hz, 1 H, ArH), 7.21–7.25 (m, 4 H, ArH), 7.31 (s, 1 H,
ArH), 7.43 (d, J = 2.1 Hz, 1 H, ArH), 7.50 (d, J = 8.3 Hz, 1 H, ArH).
Anal. Calcd for C13H15N3O: C, 68.10; H, 6.59; N, 18.33. Found: C,
68.33; H, 6.41; N, 18.53.
13C NMR (75 MHz, CDCl3): d = 29.7, 39.0, 48.9, 126.7, 126.8,
127.6, 129.88, 129.90, 131.1, 131.2, 132.0, 132.2, 135.1.
Synthesis 2010, No. 16, 2731–2748 © Thieme Stuttgart · New York

2740
A. Mishra et al.
PAPER
Methyl (E)-3-(4-Chlorophenyl)-2-{[(prop-2-ynyl)tosylami-
MS (ES+): m/z = 449.2 [M+ + 1].
no]methyl}prop-2-enoate (9d)
Yellow solid; yield: 2.20 g (88%); mp 110–110 °C; Rf = 0.23
(EtOAc–hexanes, 3:17).
Anal. Calcd for C20H18Cl2N4O2S: C, 53.46; H, 4.04; N, 12.47.
Found: C, 53.15; H, 4.32; N, 12.55.
4-Benzyl-6-(2,4-dichlorobenzyl)-4,5-dihydrotetrazolo[1,5-a]py-
rimidine (25g) and 4-Benzyl-6-(2,4-dichlorobenzyl)-4,7-dihy-
drotetrazolo[1,5-a]pyrimidine (26g)
White solid; yield: 0.087 g (87%); ratio 25g/26g 1:1; mp 142–143
°C; Rf = 0.23 (EtOAc–hexanes, 1:1).
IR (KBr): 1714 (CO2CH3), 3307 cm–1 (≡CH).
1H NMR (300 MHz, CDCl3): d = 1.82 (t, J = 2.4 Hz, 1 H, ≡CH),
2.41 (s, 3 H, CH3), 3.79 (s, 3 H, OCH3), 4.06 (d, J = 2.4 Hz, 2 H,
CH2), 4.23 (s, 2 H, CH2), 7.22 (d, J = 8.2 Hz, 2 H, ArH), 7.32–7.40
(m, 4 H, ArH), 7.51 (d, J = 8.3 Hz, 2 H, ArH), 7.82 (s, 1 H, =CH).
13C NMR (75 MHz, CDCl3): d = 21.5, 37.6, 42.8, 52.3, 73.7, 128.0,
128.5, 128.7, 129.3, 131.0, 132.9, 135.0, 135.1, 142.3, 143.7,
167.5.
IR (KBr): 1614 cm–1 (C=N).
1H NMR (200 MHz, CDCl3): d = 3.39 (s, 2 H, CH2), 3.44 (s, 2 H,
CH2), 3.95 (s, 2 H, CH2), 4.64 (s, 2 H, CH2), 4.85 (s, 4 H, 2 CH2),
5.96 (s, 1 H, =CH), 6.75–6.76 (s, 1 H, =CH), 7.11 (dd, J1 = 8.2 Hz,
J2 = 1.9 Hz, 2 H, ArH), 7.19–7.24 (m, 4 H, ArH), 7.32–7.35 (m, 8
H, ArH), 7.39–7.42 (m, J = 2.0 Hz, 2 H, ArH).
13C NMR (50 MHz, CDCl3): d = 45.5, 50.5, 54.2, 126.7, 127.5,
128.2, 128.6, 128.9, 129.2, 130.0, 131.1, 132.0, 134.8, 135.2, 135.7,
155.7.
MS (ES+): m/z = 417.9 [M+ + 1].
Anal. Calcd for C21H20ClNO4S: C, 60.35; H, 4.82; N, 3.35. Found:
C, 60.54; H, 4.93; N, 3.23.
Methyl (E)-3-(4-Methylphenyl)-2-{[(prop-2-ynyl)tosylami-
no]methyl}prop-2-enoate (9f)
Orange-white solid; yield: 2.00 g (91%); mp 104–105 °C; Rf = 0.26
MS (ES+): m/z = 372.2 [M+ + 1].
(EtOAc–hexanes, 3:17).
IR (KBr): 1712 (CO2CH3), 3306 cm–1 (≡CH).
Anal. Calcd for C18H15Cl2N5: C, 58.08; H, 4.06; N, 18.81. Found:
C, 58.26; H, 4.17; N, 18.64.
1H NMR (300 MHz, CDCl3): d = 1.82 (t, J = 2.3 Hz, 1 H, ≡CH),
2.39 (s, 3 H, CH3), 2.40 (s, 3 H, CH3), 3.77 (s, 3 H, OCH3), 4.05 (d,
J = 2.3 Hz, 2 H, CH2), 4.30 (s, 2 H, CH2), 7.20–7.22 (m, 4 H, ArH),
7.32 (d, J = 7.9 Hz, 2 H, ArH), 7.55 (d, J = 8.2 Hz, 2 H, ArH), 7.85
(s, 1 H, =CH).
13C NMR (75 MHz, CDCl3): d = 21.4, 21.5, 37.4, 43.0, 52.1, 73.4,
126.7, 128.1, 129.2, 129.8, 131.5, 135.3, 139.3, 143.4, 144.0, 168.0.
Methyl (E)-3-Phenyl-2-{[(prop-2-ynyl)tosylamino]meth-
yl}prop-2-enoate (9a); Typical Procedure for 9a,c,d,f,g and 17g
To a stirred soln of 8a (2.23 g, 6.46 mmol) in anhyd DMF (10 mL)
was added K2CO3 (1.34 g, 9.69 mmol) and the mixture was stirred
for 10 min. Then 80% propargyl bromide in toluene (1.16 mL, 7.75
mmol) was added and mixture was stirred at r.t. for 2 h. When the
reaction was complete, the mixture was diluted with H2O (40 mL)
and extracted with EtOAc (3 × 30 mL). The combined organic lay-
ers were dried (anhyd Na2SO4) and concentrated to obtain the crude
product, which was purified by column chromatography (silica gel,
100–200 mesh, EtOAc–hexanes, 1:9) to yield pure 9a (1.97 g, 80%)
as a yellow solid; mp 90–91 °C; Rf = 0.25 (EtOAc–hexanes, 3:17).
MS (ES+): m/z = 397.8 [M+ + 1].
Anal. Calcd for C22H23NO4S: C, 66.48; H, 5.83; N, 3.52. Found: C,
66.35; H, 5.88; N, 3.34.
Methyl (E)-3-(2,4-Dichlorophenyl)-2-{[(prop-2-ynyl)tosylami-
no]methyl}prop-2-enoate (9g)
IR (KBr): 1712 (CO2CH3), 3308 cm–1 (≡CH).
1H NMR (300 MHz, CDCl3): d = 1.78 (t, J = 2.3 Hz, 1 H, ≡CH),
2.39 (s, 3 H, CH3), 3.79 (s, 3 H, OCH3), 4.07 (d, J = 2.4 Hz, 2 H,
CH2), 4.27 (s, 2 H, CH2), 7.19 (d, J = 8.1 Hz, 2 H, ArH), 7.39 (s, 5
H, ArH), 7.50 (d, J = 8.3 Hz, 2 H, ArH), 7.89 (s, 1 H, =CH).
13C NMR (75 MHz, CDCl3): d = 21.5, 37.6, 42.9, 52.2, 73.5, 128.1,
128.5, 128.9, 129.3, 129.6, 134.5, 135.3, 143.5, 143.7, 167.8.
White solid; yield: 1.40 g (80%); mp 131–132 °C; Rf = 0.25
(EtOAc–hexanes, 3:17).
IR (KBr): 1722 (CO2CH3), 3304 cm–1 (≡CH).
1H NMR (300 MHz, CDCl3): d = 1.75 (t, J = 2.4 Hz, 1 H, ≡CH),
2.40 (s, 3 H, CH3), 3.81 (s, 3 H, OCH3), 4.03 (d, J = 2.4 Hz, 2 H,
CH2), 4.14 (s, 2 H, CH2), 7.22 (d, J = 8.1 Hz, 2 H, ArH), 7.28 (d,
J = 1.0 Hz, 2 H, ArH), 7.45 (s, 1 H, ArH), 7.53 (d, J = 8.3 Hz, 2 H,
ArH), 7.83 (s, 1 H, =CH).
13C NMR (75 MHz, CDCl3): d = 21.6, 37.3, 42.7, 52.4, 73.5, 127.0,
128.0, 129.37, 129.41, 130.3, 131.66, 131.67, 134.8, 135.2, 135.4,
139.7, 143.7, 166.9.
MS (ES+): m/z = 383.9 [M+ + 1].
Anal. Calcd for C21H21NO4S: C, 65.78; H, 5.52; N, 3.65. Found: C,
65.89; H, 5.73; N, 3.60.
Methyl (E)-3-(2-Fluorophenyl)-2-{[(prop-2-ynyl)tosylami-
no]methyl}prop-2-enoate (9c)
White solid; yield: 1.30 g (69%); mp 92–93 °C; Rf = 0.25 (EtOAc–
hexanes, 3:17).
MS (ES+): m/z = 451.8 [M+ + 1].
Anal. Calcd for C21H19Cl2NO4S: C, 55.76; H, 4.23; N, 3.10. Found:
C, 55.68; H, 4.38; N, 3.19.
IR (KBr): 1716 (CO2CH3), 3310 cm–1 (≡CH).
1H NMR (300 MHz, CDCl3): d = 1.75 (t, J = 2.3 Hz, 1 H, ≡CH),
2.39 (s, 3 H, CH3), 3.80 (s, 3 H, OCH3), 4.06 (d, J = 2.3 Hz, 2 H,
CH2), 4.19 (s, 2 H, CH2), 7.07–7.20 (m, 4 H, ArH), 7.34–7.41 (m, 2
H, ArH), 7.50 (d, J = 8.3 Hz, 2 H, ArH), 7.82 (s, 1 H, =CH).
13C NMR (75 MHz, CDCl3): d = 21.5, 37.5, 43.14, 43.17, 52.2,
73.4, 115.5, 115.8, 122.4, 122.6, 124.0, 124.1, 128.0, 129.3, 130.4,
130.7, 130.8, 130.96, 131.01, 135.3, 136.4, 136.5, 143.5, 158.4,
161.7, 167.1.
Methyl 2-{(2,4-Dichlorophenyl)[(prop-2-ynyl)tosylami-
no]methyl}acrylate (17g)
White solid; yield: 1.40 g (80%); mp 131–132 °C; Rf = 0.32
(EtOAc–hexanes, 3:17).
IR (KBr): 1722 cm–1 (CO2CH3).
1H NMR (300 MHz, CDCl3): d = 2.06 (t, J = 2.4 Hz, 1 H, ≡CH),
2.44 (s, 3 H, CH3), 3.60 (s, 3 H, OCH3), 4.05–4.29 (m, 2 H, CH2),
5.87 (d, J = 1.3 Hz, 1 H, CH), 6.32 (s, 1 H, =CH2), 6.62 (s, 1 H,
=CH2), 7.22–7.30 (m, 4 H, ArH), 7.37 (d, J = 8.4 Hz, 1 H, ArH),
7.70 (d, J = 8.3 Hz, 2 H, ArH).
MS (ES+): m/z = 402.2 [M+ + 1].
Anal. Calcd for C21H20FNO4S: C, 62.83; H, 5.02; N, 3.49. Found:
C, 62.66; H, 5.10; N, 3.42.
Synthesis 2010, No. 16, 2731–2748 © Thieme Stuttgart · New York

PAPER
Fused Triazoles and Tetrazoles via Intramolecular Cycloaddition
2741
13C NMR (75 MHz, CDCl3): d = 21.8, 36.6, 52.4, 59.4, 73.1, 127.4,
128.1, 129.4, 129.9, 130.7, 131.1, 134.2, 134.9, 137.4, 138.0, 143.8,
165.8.
1H NMR (200 MHz, CDCl3): d = 3.43 (d, J = 0.6 Hz, 2 H, CH2),
3.47 (d, J = 1.3 Hz, 2 H, CH2), 3.73 (s, 2 H, CH2), 3.84 (s, 2 H, CH2),
4.04 (s, 4 H, 2 CH2), 6.61 (s, 1 H, =CH), 6.71 (s, 1 H, =CH), 6.94–
7.09 (m, 4 H, ArH), 7.17–7.37 (m, 14 H, ArH).
13C NMR (75 MHz, CDCl3): d = 47.3, 49.7, 53.0, 53.2, 53.5, 55.8,
115.3, 115.4, 115.7, 123.8, 124.0, 124.2, 127.1, 127.2, 128.0, 128.2,
128.3, 128.4, 128.5, 128.6, 129.2, 129.3, 129.4, 130.7, 137.0, 139.7.
MS (ES+): m/z = 451.8 [M+ + 1].
Anal. Calcd for C21H19Cl2NO4S: C, 55.76; H, 4.23; N, 3.10. Found:
C, 55.68; H, 4.38; N, 3.19.
3-(Methylsulfonyloxy)-1-phenyl-2-{[(prop-2-ynyl)tosylami-
no]methyl}prop-1-ene (11a); Typical Procedure for 11a,c,d,f,g
and 18a,e–h
MS (ES+): m/z = 297.1 [M+ + 1].
Anal. Calcd for C17H17FN4: C, 68.90; H, 5.78; N, 18.91. Found: C,
69.05; H, 6.03; N, 18.67.
To a stirred soln of 10a (0.80 g, 2.25 mmol) in anhyd CH2Cl2 (40
mL) was added Et3N (0.48 mL, 3.38 mmol) and then MsCl (0.22
mL, 2.93 mmol) in CH2Cl2 (15 mL) was added dropwise at 0 °C.
The mixture was stirred at r.t. for 30 min. When the reaction was
complete it was quenched with H2O (30 mL) and partitioned in a
separating funnel. The organic layer was collected and the aqueous
layer was extracted with CHCl3 (2 × 20 mL). The combined organic
layers were washed with brine (50 mL), dried (anhyd Na2SO4), and
concentrated to give crude 11a which was used in next step without
purification.
(E/Z)-2-(Azidomethyl)-N-benzyl-3-(4-methylphenyl)prop-2-en-
1-amine [(E/Z)-19f]
Brown oil; yield: 1.60 g (77%); ratio of diastereomers 5:4; Rf = 0.29
(EtOAc–hexanes, 1:4).
IR (neat): 2098 (N3), 3372 cm–1 (NH).
1H NMR (300 MHz, CDCl3): d = 2.36 (s, 6 H, 2 CH3), 3.48 (s, 2 H,
CH2), 3.74 (s, 2 H, CH2), 3.78–3.83 (m, 4 H, 2 CH2), 4.05 (s, 2 H,
CH2), 4.09 (s, 2 H, CH2), 4.84 (br s, 2 H, 2 NH), 6.64 (s, 1 H, =CH),
6.73 (s, 1 H, =CH), 7.10–7.44 (m, 16 H, ArH), 7.79 (s, 2 H, ArH).
13C NMR (75 MHz, CDCl3): d = 21.5, 21.6, 49.9, 53.3, 53.5, 53.6,
54.4, 127.3, 127.4, 128.4, 128.6, 128.88, 128.93, 129.0, 129.1,
129.2, 129.4, 129.5, 130.18, 130.20, 132.0, 134.9, 136.6, 139.7,
140.7.
3-Azido-1-phenyl-2-{[(prop-2-ynyl)tosylamino]methyl}prop-1-
ene (12a); Typical Procedure for 12a,c,d,f,g
To a stirred soln of 11a (0.65 g, 1.50 mmol) in DMF (5 mL) was
added NaN3 (0.20 g, 3.00 mmol) in H2O (1.0 mL) and mixture was
allowed to react at r.t. for 1 h. When the reaction was complete, the
mixture was diluted with H2O (20 mL) and extracted with EtOAc
(20 mL). The aqueous layer was separated and extracted with
EtOAc (3 × 10 mL). The combined organic layers were dried (an-
hyd Na2SO4) and concentrated to crude 12a which was used in next
step without purification.
MS (ES+): m/z = 293.1 [M+ + 1].
Anal. Calcd for C18H20N4: C, 73.94; H, 6.89; N, 19.16. Found: C,
73.76; H, 6.95; N, 19.20.
(E/Z)-2-(Azidomethyl)-N-benzyl-3-(2,4-dichlorophenyl)prop-2-
en-1-amine [(E/Z)-19g]
Brown oil; yield: 0.80 g (78%); ratio of diastereomers 4:1; Rf = 0.30
(E,Z)-2-(Azidomethyl)-N-benzyl-3-phenylprop-2-en-1-amine
[(E/Z)-19a]; Typical Procedure for 19a,e–h and 20a,e–h
(EtOAc–hexanes, 1:4).
To a stirred soln of 18a (1.50 g, 5.62 mmol) in anhyd THF (15 mL)
was added BnNH2 (1.8 mL, 16.85 mmol) and KI (cat.) and the mix-
ture was heated at 80 °C in an oil bath for 2 h. When the reaction
was complete (TLC monitoring), THF was evaporated under vacu-
um and the residue was extracted with EtOAc (3 × 30 mL). The
combined organic layers were washed with brine (50 mL), dried
(anhyd Na2SO4), and concentrated to yield the crude product. Puri-
fication by column chromatography (silica gel, 100–200 mesh,
EtOAc–hexanes, 1:4) afforded the diastereomeric mixture of (E/Z)-
19a (1.25 g, 80%) as brown oil; Rf = 0.26 (EtOAc–hexanes, 1:4).
IR (neat): 2102 (N3), 3433 cm–1 (NH).
1H NMR (200 MHz, CDCl3): d = 3.34 (d, J = 0.7 Hz, 2 H, CH2),
3.50 (s, 2 H, CH2), 3.69 (s, 2 H, CH2), 3.85 (s, 2 H, CH2), 3.95 (s, 2
H, CH2), 4.12 (d, J = 1.0 Hz, 2 H, CH2), 4.84 (d, J = 1.3 Hz, 2 H, 2
NH), 6.63 (s, 1 H, =CH), 6.76 (s, 1 H, =CH), 7.14–7.44 (m, 16 H,
ArH).
13C NMR (75 MHz, CDCl3): d = 46.9, 49.4, 53.0, 53.3, 55.7, 126.8,
127.0, 127.2, 127.5, 127.6, 128.0, 128.2, 128.3, 128.4, 128.5, 128.6,
129.3, 129.4, 129.8, 130.8, 131.3, 131.4, 133.1, 133.3, 133.9, 134.0,
134.3, 134.5, 137.4, 139.6, 139.9.
IR (neat): 2101 (N3), 3451 cm–1 (NH).
1H NMR (200 MHz, CDCl3): d = 3.49 (s, 4 H, 2 CH2), 3.73 (s, 2 H,
CH2), 3.85 (s, 2 H, CH2), 4.07 (s, 2 H, CH2), 4.08 (s, 2 H, CH2), 6.67
(s, 1 H, =CH), 6.77 (s, 1 H, =CH), 7.22–7.44 (m, 20 H, ArH).
13C NMR (50 MHz, CDCl3): d = 49.6, 53.4, 54.0, 56.6, 56.8, 126.6,
127.1, 127.2, 127.4, 127.5, 128.1, 128.2, 128.3, 128.4, 128.5, 128.6,
128.8, 128.9, 129.0, 129.2, 129.5, 130.9, 131.6, 131.7, 135.2, 135.4,
136.4, 140.2.
MS (ES+): m/z = 347.1 [M+ + 1].
Anal. Calcd for C17H16Cl2N4: C, 58.80; H, 4.64; N, 16.13. Found:
C, 59.10; H, 4.45; N, 16.32.
(E)-2-(Azidomethyl)-N-benzyl-3-(2,6-dichlorophenyl)prop-2-
en-1-amine [(E)-19h]
Brown oil; yield: 0.83 g (80%); Rf = 0.31 (EtOAc–hexanes, 1:4).
MS (ES+): m/z = 279.1 [M+ + 1].
IR (neat): 2109 (N3), 3448 cm–1 (NH).
1H NMR (200 MHz, CDCl3): d = 3.55 (s, 2 H, CH2), 3.80 (s, 2 H,
CH2), 3.88 (s, 2 H, CH2), 6.47 (s, 1 H, =CH), 7.15–7.23 (m, 2 H,
ArH), 7.26–7.37 (m, 6 H, ArH).
13C NMR (50 MHz, CDCl3): d = 50.6, 52.4, 53.2, 125.1, 127.5,
128.4, 128.7, 128.9, 129.5, 134.5, 135.3, 139.5, 140.6.
Anal. Calcd for C17H18N4: C, 73.35; H, 6.52; N, 20.13. Found: C,
73.62; H, 6.50; N, 20.41.
(E/Z)-2-(Azidomethyl)-N-benzyl-3-(4-fluorophenyl)prop-2-en-
1-amine [(E/Z)-19e]
Brown oil; yield: 1.47 g (75%); ratio of diastereomers 1:1; Rf = 0.27
(EtOAc–hexanes, 1:4).
MS (ES+): m/z = 347.1 [M+ + 1].
IR (neat): 2101 (N3), 3421 cm–1 (NH).
Anal. Calcd for C17H16Cl2N4: C, 58.80; H, 4.64; N, 16.13. Found:
C, 59.02; H, 4.93; N, 15.87.
Synthesis 2010, No. 16, 2731–2748 © Thieme Stuttgart · New York

2742
A. Mishra et al.
PAPER
(E/Z)-2-(Azidomethyl)-3-phenyl-N-propylprop-2-en-1-amine
[(E/Z)-20a]
CH2), 4.08 (s, 2 H, CH2), 6.61 (s, 1 H, =CH), 6.69 (s, 1 H, =CH),
7.17–7.26 (m, 4 H, ArH), 7.43 (s, 2 H, ArH).
Brown oil; yield: 1.00 g (89%); ratio of diastereomers 1:1; Rf = 0.24
(EtOAc–hexanes, 1:4).
IR (neat): 2101 (N3), 3295 cm–1 (NH).
13C NMR (75 MHz, CDCl3): d = 11.7, 11.8, 22.9, 23.0, 47.6, 49.4,
51.0, 51.3, 53.6, 55.5, 126.8, 127.0, 127.2, 128.0, 129.3, 129.4,
131.3, 131.5, 133.3.
1H NMR (200 MHz, CDCl3): d = 0.95 (t, J = 7.5 Hz, 6 H, 2 CH3),
1.50–1.65 (m, 4 H, 2 CH2), 2.47–2.55 (m, 2 H, CH2), 2.63 (t, J = 6.5
Hz, 2 H, CH2), 3.08–3.12 (m, 4 H, 2 CH2), 3.46 (s, 2 H, CH2), 4.03–
4.06 (m, 2 H, CH2), 4.66 (br s, 2 H, 2 NH), 6.67 (s, 1 H, =CH), 6.76
(s, 1 H, =CH), 7.27–7.35 (m, 10 H, ArH).
13C NMR (50 MHz, CDCl3): d = 11.5, 12.1, 23.3, 23.8, 40.6, 35.4,
51.5, 51.8, 127.69, 127.75, 128.7, 128.8, 129.15, 129.20, 132.0,
135.0, 135.2, 136.6.
MS (ES+): m/z = 299.1 [M+ + 1].
Anal. Calcd for C13H16Cl2N4 C, 52.19; H, 5.39; N, 18.73. Found: C,
52.32; H, 5.57; N, 18.72.
(E)-2-(Azidomethyl)-3-(2,6-dichlorophenyl)-N-propylprop-2-
en-1-amine [(E)-20h]
Green oil; yield: 1.00 g (75%); Rf = 0.29 (EtOAc–hexanes, 1:4).
IR (neat): 2102 (N3), 3445 cm–1 (NH).
1H NMR (200 MHz, CDCl3): d = 0.95 (t, J = 7.4 Hz, 3 H, CH3),
1.50–1.58 (m, 2 H, CH2), 2.66 (t, J = 6.9 Hz, 2 H, CH2), 3.53 (s, 2
H, CH2), 3.76 (s, 2 H, CH2), 6.43 (s, 1 H, =CH), 7.14–7.22 (m, 1 H,
ArH), 7.32–7.36 (m, 2 H, ArH).
MS (ES+): m/z = 231.0 [M+ + 1].
Anal. Calcd for C13H18N4: C, 67.80; H, 7.88; N, 24.33. Found: C,
67.92; H, 7.56; N, 24.52.
(E/Z)-2-(Azidomethyl)-3-(4-fluorophenyl)-N-propylprop-2-en-
1-amine [(E/Z)-20e]
Brown oil; yield: 1.00 g (88%); ratio of diastereomers 1:1; Rf = 0.23
(EtOAc–hexanes, 1:4).
13C NMR (50 MHz, CDCl3): d = 12.2, 23.6, 50.6, 51.3, 53.1, 124.6,
128.3, 129.5, 134.6, 135.3, 139.7.
MS (ES+): m/z = 299.0 [M+ + 1].
IR (neat): 2101 (N3), 3296 cm–1 (NH).
Anal. Calcd for C13H16Cl2N4: C, 52.19; H, 5.39; N, 18.73. Found:
C, 52.10; H, 5.42; N, 18.44.
1H NMR (300 MHz, CDCl3): d = 0.97 (t, J = 7.3 Hz, 6 H, 2 CH3),
1.54–1.64 (m, 4 H, 2 CH2), 2.51 (t, J = 7.2 Hz, 2 H, CH2), 2.61 (t,
J = 7.2 Hz, 2 H, CH2), 3.10–3.14 (m, 4 H, 2 CH2), 3.42–3.44 (m, 2
H, CH2), 4.01 (s, 2 H, CH2), 4.25 (br s, 2 H, 2 NH), 6.60 (s, 1 H,
=CH), 6.70 (s, 1 H, =CH), 7.01–7.07 (m, 4 H, ArH), 7.18–7.25 (m,
4 H, ArH).
13C NMR (75 MHz, CDCl3): d = 11.5, 12.1, 23.6, 23.8, 40.7, 45.4,
51.7, 52.0, 115.4, 115.5, 115.8, 116.0, 130.3, 130.6, 130.7, 130.9,
131.0, 132.6, 135.8, 136.0.
(E/Z)-N-[2-(Azidomethyl)-3-phenylprop-2-enyl)-N-benzylcyan-
amide [(E/Z)-21a]; Typical Procedure for 21a,e–h and 22a,e–h
To a stirred soln of mixture of (E/Z)-19a (0.90 g, 3.24 mmol) in
MeOH (15 mL) was added CNBr (0.41 g, 3.89 mmol) and NaHCO3
(0.27 g, 3.24 mmol) and the mixture was stirred at r.t. for 15 min.
When the reaction was complete, MeOH was removed and the res-
idue was diluted with EtOAc (40 mL) and H2O (40 mL). The aque-
ous layer was separated and extracted with EtOAc (4 × 20 mL). The
combined organic layers were dried (anhyd Na2SO4) and evaporat-
ed under vacuum to obtain a residue, that was purified by column
chromatography (silica gel, EtOAc–hexanes, 3:17) to yield (E/Z)-
21a (0.76 g, 78%) as a brown oil; ratio of diastereomers 1:1;
Rf = 0.32 (EtOAc–hexanes, 1:4).
IR (ES+): m/z = 249.0 [M+ + 1].
Anal. Calcd for C13H17FN4: C, 62.88; H, 6.90; N, 22.56. Found: C,
62.98; H, 7.07; N, 22.63.
(E/Z)-2-(Azidomethyl)-3-(4-methylphenyl)-N-propylprop-2-en-
1-amine [(E/Z)-20f]
Red oil; yield: 0.90 g (69%); ratio of diastereomers 4:1; Rf = 0.20
(EtOAc–hexanes, 3:1).
IR (neat): 2100 (N3), 2211 cm–1 (CN).
1H NMR (200 MHz, CDCl3): d = 3.77 (t, J = 1.0 Hz, 4 H, 2 CH2),
4.06–4.10 (m, 6 H, 3 CH2), 4.27 (s, 2 H, CH2), 6.76 (s, 1 H, =CH),
6.93 (s, 1 H, =CH), 7.14–7.42 (m, 20 H, ArH).
13C NMR (75 MHz, CDCl3): d = 47.7, 48.7, 55.1, 55.4, 55.6, 117.7,
128.0, 128.2, 128.59, 128.62, 128.7, 128.76, 128.80, 128.85,
128.93, 129.0, 129.1, 129.7, 129.8, 134.1, 134.4, 134.9, 135.8,
136.2.
IR (neat): 2101 (N3), 3292 cm–1 (NH).
1H NMR (300 MHz, CDCl3): d = 0.97 (t, J = 7.4 Hz, 6 H, 2 CH3),
1.57–1.67 (m, 4 H, 2 CH2), 2.32 (s, 3 H, CH3), 2.35 (s, 3 H, CH3),
2.52 (t, J = 7.1 Hz, 1 H, CH2), 2.61 (t, J = 7.1 Hz, 1 H, CH2), 3.07–
3.14 (m, 4 H, 2 CH2), 3.45 (d, J = 7.3 Hz, 2 H, CH2), 4.01 (s, 2 H,
CH2), 4.05 (s, 2 H, CH2), 4.42 (br s, 2 H, 2 NH), 6.61 (s, 1 H, =CH),
6.71 (s, 1 H, =CH), 7.09–7.16 (m, 8 H, ArH).
MS (ES+): m/z = 304.2 [M+ + 1].
Anal. Calcd for C18H17N5: C, 71.27; H, 5.65; N, 23.09. Found: C,
71.16; H, 5.74; N, 23.20.
13C NMR (75 MHz, CDCl3): d = 11.5, 23.8, 40.6, 45.4, 111.4,
127.8, 129.1, 129.4, 129.5, 132.5.
(E/Z)-N-[2-(Azidomethyl)-3-(4-fluorophenyl)prop-2-enyl]-N-
benzylcyanamide [(E/Z)-21e]
Brown oil; yield: 0.49 g (74%); ratio of diastereomers 1:1; Rf = 0.32
MS (ES+): m/z = 245.1 [M+ + 1].
Anal. Calcd for C14H20N4: C, 68.82; H, 8.25; N, 22.93. Found: C,
68.72; H, 8.35; N, 22.91.
(EtOAc–hexanes, 1:4).
IR (neat): 2103 (N3), 2214 cm–1 (CN).
(E/Z)-2-(Azidomethyl)-3-(2,4-dichlorophenyl)-N-propylprop-2-
en-1-amine [(E/Z)-20g]
Brown oil; yield: 0.70 g (78%); ratio of diastereomers 1:1; Rf = 0.34
(EtOAc–hexanes, 1:4).
1H NMR (300 MHz, CDCl3): d = 3.73 (s, 2 H, CH2), 3.80 (s, 2 H,
CH2), 4.03 (s, 2 H, CH2), 4.08 (s, 4 H, 2 CH2), 4.26 (s, 2 H, CH2),
6.67 (s, 1 H, =CH), 6.82 (s, 1 H, =CH), 7.08–7.18 (m, 8 H, ArH),
7.28–7.30 (m, 4 H, ArH), 7.36–7.40 (m, 6 H, ArH).
13C NMR (50 MHz, CDCl3): d = 48.7, 48.8, 49.4, 55.0, 55.1, 55.6,
116.0, 116.4, 122.9, 124.5, 124.6, 128.6, 128.9, 129.0, 129.1, 129.3,
129.5, 130.4, 130.5, 130.6, 130.7, 130.9, 131.0, 132.6, 134.4, 134.7,
162.8.
IR (neat): 2102 (N3), 3451 cm–1 (NH).
1H NMR (200 MHz, CDCl3): d = 0.85–0.99 (m, 6 H, 2 CH3), 1.34–
1.59 (m, 4 H, 2 CH2), 2.47 (t, J = 7.1 Hz, 2 H, CH2), 2.64 (t, J = 7.5
Hz, 2 H, CH2), 3.33 (s, 2 H, CH2), 3.49 (s, 2 H, CH2), 3.93 (s, 2 H,
Synthesis 2010, No. 16, 2731–2748 © Thieme Stuttgart · New York

PAPER
Fused Triazoles and Tetrazoles via Intramolecular Cycloaddition
2743
MS (ES+): m/z = 322.2 [M+ + 1].
6.82 (s, 1 H, =CH), 6.94 (s, 1 H, =CH), 7.23–7.26 (m, 5 H, ArH),
7.30–7.41 (m, 5 H, ArH).
13C NMR (50 MHz, CDCl3): d = 11.4, 11.5, 21.2, 21.4, 49.1, 49.3,
53.5, 53.7, 55.4, 56.7, 128.4, 128.5, 129.0, 129.1, 129.2, 130.5,
135.3, 135.7, 136.3.
Anal. Calcd for C18H16FN5: C, 67.28; H, 5.02; N, 21.79. Found: C,
67.42; H, 5.13; N, 21.52.
(E/Z)-N-[2-(Azidomethyl)-3-(4-methylphenyl)prop-2-enyl]-N-
benzylcyanamide [(E/Z)-21f]
Brown oil; yield: 0.42 g (78%); ratio of diastereomers 1:1; Rf = 0.34
(EtOAc–hexanes, 1:4).
MS (ES+): m/z = 256.2 [M+ + 1].
Anal. Calcd for C14H17N5: C, 65.86; H, 6.71; N, 27.43. Found: C,
66.04; H, 6.92; N, 27.30.
IR (neat): 2102 (N3), 2213 cm–1 (CN).
1H NMR (300 MHz, CDCl3): d = 2.32 (s, 3 H, CH3), 2.36 (s, 3 H,
CH3), 3.75 (d, J = 2.3 Hz, 2 H, CH2), 3.78 (s, 2 H, CH2), 4.07–4.11
(m, 6 H, 3 CH2), 4.25 (d, J = 3.0 Hz, 2 H, CH2), 6.71 (s, 1 H, =CH),
6.88 (s, 1 H, =CH), 7.06–7.19 (m, 8 H, ArH), 7.29–7.37 (m, 10 H,
ArH).
13C NMR (75 MHz, CDCl3): d = 21.6, 21.7, 48.2, 48.4, 54.5, 54.6,
55.7, 55.8, 127.0, 129.0, 129.1, 129.2, 129.3, 129.5, 129.65, 129.71,
130.0, 131.7, 134.89, 138.93.
(E/Z)-N-[2-(Azidomethyl)-3-(4-fluorophenyl)prop-2-enyl]-N-
propylcyanamide [(E/Z)-22e]
Colorless oil; yield: 0.90 g (84%); mixture of diastereomers 10:7;
Rf = 0.25 (EtOAc–hexanes, 1:4).
IR (neat): 2101 (N3), 2210 cm–1 (CN).
1H NMR (300 MHz, CDCl3): d = 0.96 (t, J = 7.4 Hz, 3 H, CH3),
1.03 (t, J = 7.4 Hz, 3 H, CH3), 1.68–1.71 (m, 2 H, CH2), 1.73–1.83
(m, 2 H, CH2), 2.94 (t, J = 7.4 Hz, 2 H, CH2), 3.06 (t, J = 7.4 Hz, 2
H, CH2), 3.80–3.83 (m, 4 H, 2 CH2), 4.09 (d, J = 5.1 Hz, 4 H, 2
CH2), 6.79 (s, 1 H, =CH), 6.90 (s, 1 H, =CH), 7.06–7.12 (m, 4 H,
ArH), 7.21–7.28 (m, 4 H, ArH).
13C NMR (50 MHz, CDCl3): d = 11.4, 11.5, 21.2, 21.4, 49.0, 49.2,
53.7, 53.9, 55.4, 56.6, 115.8, 116.3, 130.7, 130.8, 130.9, 131.0,
131.1, 131.4, 134.5, 135.2, 165.2.
MS (ES+): m/z = 318.2 [M+ + 1].
Anal. Calcd for C19H19N5: C, 71.90; H, 6.03; N, 22.07. Found: C,
72.12; H, 6.32; N, 21.94.
(E/Z)-N-[2-(Azidomethyl)-3-(2,4-dichlorophenyl)prop-2-enyl]-
N-benzylcyanamide [(E/Z)-21g]
Brown oil; yield: 0.75 g (87%); ratio of diastereomers 2:1; Rf = 0.29
(EtOAc–hexanes, 1:4).
IR (neat): 2102 (N3), 2211 cm–1 (CN).
1H NMR (200 MHz, CDCl3): d = 3.51 (d, J = 8.1 Hz, 2 H, CH2),
3.64 (s, 2 H, CH2), 3.79 (s, 2 H, CH2), 3.96 (s, 2 H, CH2), 4.09 (s, 2
H, CH2), 4.28 (s, 2 H, CH2), 6.69 (s, 1 H, =CH), 6.83 (s, 1 H, =CH),
7.05–7.17 (m, 4 H, ArH), 7.31–7.51 (m, 12 H, ArH).
13C NMR (50 MHz, CDCl3): d = 48.2, 49.1, 54.7, 54.9, 55.5, 55.7,
127.5, 127.6, 128.9, 129.1, 129.2, 129.3, 129.4, 129.5, 129.9, 130.0,
131.6, 131.9, 132.3, 132.4, 132.7, 132.8, 134.6, 134.9.
MS (ES+): m/z = 274.2 [M+ + 1].
Anal. Calcd for C14H16FN5: C, 61.52; H, 5.90; N, 25.62. Found: C,
61.35; H, 6.10; N, 25.69.
(E/Z)-N-[2-(Azidomethyl)-3-(4-methylphenyl)prop-2-enyl]-N-
propylcyanamide [(E/Z)-22f]
Red oil; yield: 0.80 g (86%); mixture of diastereomers 10:6;
Rf = 0.27 (EtOAc–hexanes, 1:4).
IR (neat): 2101 (N3), 2210 cm–1 (CN).
1H NMR (200 MHz, CDCl3): d = 0.93–1.05 (m, 6 H, 2 CH3), 1.56–
1.80 (m, 4 H, 2 CH2), 2.37 (s, 6 H, 2 CH3), 2.90 (t, J = 7.1 Hz, 2 H,
CH2), 3.03 (t, J = 7.5 Hz, 2 H, CH2), 3.82 (s, 4 H, 2 CH2), 4.06 (s, 2
H, CH2), 4.12 (s, 2 H, CH2), 6.78 (s, 1 H, =CH), 6.89 (s, 1 H, =CH),
7.17–7.26 (m, 8 H, ArH).
MS (ES+): m/z = 372.2 [M+ + 1].
Anal. Calcd for C18H15Cl2N5: C, 58.08; H, 4.06; N, 18.81. Found:
C, 58.23; H, 3.87; N, 18.69.
(Z)-N-[2-(Azidomethyl)-3-(2,6-dichlorophenyl)prop-2-enyl]-N-
benzylcyanamide [(Z)-21h]
Brown solid; yield: 0.69 g (88%); mp 142–143 °C; Rf = 0.29
13C NMR (50 MHz, CDCl3): d = 11.4, 11.5, 21.2, 21.4, 21.7, 49.2,
49.3, 53.4, 53.7, 55.6, 56.8, 129.1, 129.2, 129.7, 129.8, 132.4,
135.7, 136.4, 138.5.
(EtOAc–hexanes, 1:4).
IR (KBr): 2113 (N3), 2211 cm–1 (CN).
1H NMR (200 MHz, CDCl3): d = 3.85 (s, 4 H, 2 CH2), 4.30 (s, 2 H,
CH2), 6.45 (s, 1 H, =CH), 7.20–7.28 (m, 1 H, ArH), 7.36–7.41 (m,
7 H, ArH).
13C NMR (50 MHz, CDCl3): d = 49.9, 53.8, 55.1, 128.6, 128.8,
129.2, 129.3, 129.5, 130.2, 133.1, 134.6, 134.7, 135.1.
MS (ES+): m/z = 372.2 [M+ + 1].
MS (ES+): m/z = 270.2 [M+ + 1].
Anal. Calcd for C15H19N5: C, 66.89; H, 7.11; N, 26.00. Found: C,
67.07; H, 6.96; N, 26.15.
(E/Z)-N-[2-(Azidomethyl)-3-(2,4-dichlorophenyl)prop-2-enyl]-
N-propylcyanamide (22g)
Brown oil; yield: 0.66 g (87%); mixture of diastereomers 10:8;
Rf = 0.29 (EtOAc–hexanes, 1:4).
IR (neat): 2103 (N3), 2212 cm–1 (CN).
Anal. Calcd for C18H15Cl2N5: C, 58.08; H, 4.06; N, 18.81. Found:
C, 58.14; H, 3.93; N, 18.76.
1H NMR (200 MHz, CDCl3): d = 0.89–1.05 (m, 6 H, 2 CH3), 1.54–
1.65 (m, 2 H, CH2), 1.70–1.81 (m, 2 H, CH2), 2.88 (t, J = 7.3 Hz, 2
H, CH2), 3.05 (t, J = 7.4 Hz, 2 H, CH2), 3.69 (s, 2 H, CH2), 3.86 (s,
2 H, CH2), 3.97 (s, 2 H, CH2), 4.10 (s, 2 H, CH2), 6.73 (s, 1 H, =CH),
6.81 (s, 1 H, =CH), 7.15–7.31 (m, 4 H, ArH), 7.45 (s, 2 H, ArH).
13C NMR (75 MHz, CDCl3): d = 11.3, 11.5, 21.2, 21.4, 49.2, 49.5,
53.4, 53.7, 54.8, 56.0, 117.4, 117.6, 127.6, 128.8, 129.0, 129.6,
130.0, 131.3, 131.6, 131.9, 132.45, 132.54, 133.1, 133.2, 134.8,
134.9, 135.19, 135.24.
(E/Z)-N-[2-(Azidomethyl)-3-phenylprop-2-enyl]-N-propyl-
cyanamide [(E/Z)-22a]
Brown oil; yield: 0.84 g (80%); mixture of diastereomers 2:1;
Rf = 0.30 (EtOAc–hexanes, 1:4).
IR (neat): 2100 (N3), 2210 cm–1 (CN).
1H NMR (300 MHz, CDCl3): d = 0.94 (t, J = 3.8 Hz, 3 H, CH3),
1.02 (t, J = 7.4 Hz, 3 H, CH3), 1.57–1.64 (m, 2 H, CH2), 1.72–1.79
(m, 2 H, CH2), 2.90 (t, J = 7.4 Hz, 2 H, CH2), 3.04 (t, J = 7.4 Hz, 2
H, CH2), 3.83 (s, 4 H, 2 CH2), 4.08 (s, 2 H, CH2), 4.12 (s, 2 H, CH2),
MS (ES+): m/z = 324.2 [M+ + 1].
Synthesis 2010, No. 16, 2731–2748 © Thieme Stuttgart · New York

2744
A. Mishra et al.
PAPER
Anal. Calcd for C14H15Cl2N5: C, 51.86; H, 4.66; N, 21.60. Found:
C, 51.97; H, 4.82; N, 21.43.
(E/Z)-4-Benzyl-6-(4-methylbenzylidene)-4,5,6,7-tetrahydrotet-
razolo[1,5-a]pyrimidine [(E/Z)-23f]
Brown oil; yield: 0.30 g (86%); ratio of diastereomers 5:2; Rf = 0.23
(EtOAc–hexanes, 1:1).
IR (neat): 1610 cm–1 (C=N).
(Z)-N-[2-(Azidomethyl)-3-(2,6-dichlorophenyl)prop-2-enyl]-N-
propylcyanamide [(Z)-22h]
Colorless oil; yield: 0.86 g (80%); Rf = 0.27 (EtOAc–hexanes, 1:4).
IR (neat): 2102 (N3), 2212 cm–1 (CN).
1H NMR (200 MHz, CDCl3): d = 1.01 (t, J = 7.4 Hz, 3 H, CH3),
1.71–1.81 (m, 2 H, CH2), 3.07 (t, J = 7.3 Hz, 2 H, CH2), 3.81 (s, 2
H, CH2), 3.93 (s, 2 H, CH2), 6.48 (s, 1 H, =CH), 7.21 (d, J = 8.8 Hz,
1 H, ArH), 7.37 (d, J = 7.4 Hz, 2 H, ArH).
13C NMR (75 MHz, CDCl3): d = 11.5, 21.3, 49.9, 53.0, 55.3, 117.9,
128.2, 128.4, 128.5, 129.7, 130.2, 133.1, 135.0, 135.1.
1H NMR (200 MHz, CDCl3): d = 2.35–2.37 (m, 6 H, 2 CH3), 3.88
(s, 2 H, CH2), 4.00 (s, 2 H, CH2), 4.69 (s, 2 H, CH2), 4.77 (s, 2 H,
CH2), 4.96 (s, 2 H, CH2), 5.14 (s, 2 H, CH2), 6.73 (s, 1 H, =CH),
6.83–6.92 (m, 2 H, =CH, ArH), 7.05–7.08 (m, 4 H, ArH), 7.18–7.38
(m, 13 H, ArH).
13C NMR (50 MHz, CDCl3): d = 21.7, 45.7, 45.9, 52.2, 54.4, 123.1,
126.0, 128.6, 128.9, 129.0, 129.2, 129.3, 129.7, 129.9, 130.1, 131.9,
132.1, 132.3, 135.9, 138.9.
MS (ES+): m/z = 324.1 [M+ + 1].
MS (ES+): m/z = 318.2 [M+ + 1].
Anal. Calcd for C14H15Cl2N5: C, 51.86; H, 4.66; N, 21.60. Found:
C, 51.82; H, 4.74; N, 21.54.
HRMS (EI): m/z [M]+ calcd for C19H19N5: 317.1640; found:
317.1691.
(E/Z)-4-Benzyl-6-benzylidene-4,5,6,7-tetrahydrotetrazolo[1,5-
a]pyrimidine [(E/Z)-23a]; Typical Procedure for 23a,e–h,
24a,e–h, and 30a,e–g
(E)-4-Benzyl-6-(2,4-dichlorobenzylidene)-4,5,6,7-tetrahydro-
tetrazolo[1,5-a]pyrimidine [(E)-23g]
White solid; yield: 0.53 g (88%); mp 156–157 °C; Rf = 0.21
(EtOAc–hexanes, 1:1).
Compound (E/Z)-21a (0.50 g, 1.65 mmol) was dissolved in anhyd
DMF and heated at 90 °C for 2 h. Then the mixture was cooled to
r.t., diluted with H2O (30 mL), and extracted with EtOAc (30 mL).
The aqueous layer was separated and extracted with EtOAc (3 × 20
mL). The combined organic layers were dried (anhyd Na2SO4) and
evaporated to furnish a residue, which was purified by column chro-
matography (silica gel, 230–400 mesh, EtOAc–hexanes, 3:7) to fur-
nish (E/Z)-23a (0.38 g, 76%) as a brown oil; ratio of diastereomers
2:1; Rf = 0.23 (EtOAc–hexanes, 1:1).
IR (KBr): 1614 cm–1 (C=N).
1H NMR (300 MHz, CDCl3): d = 3.81 (s, 2 H, CH2), 4.68 (s, 2 H,
CH2), 5.03 (d, J = 1.2 Hz, 2 H, CH2), 6.72 (d, J = 8.3 Hz, 1 H, ArH),
6.80 (s, 1 H, =CH), 7.03 (dd, J1 = 8.2 Hz, J2 = 2.0 Hz, 1 H, ArH),
7.26–7.29 (m, 2 H, ArH), 7.32–7.34 (m, 3 H, ArH), 7.40 (d, J = 2.0
Hz, 1 H, ArH).
13C NMR (50 MHz, CDCl3): d = 45.5, 50.5, 54.2, 126.7, 127.5,
128.2, 128.6, 128.9, 129.2, 130.0, 131.1, 132.0, 134.8, 135.2, 135.7,
155.7.
IR (neat): 1662 cm–1 (C=N).
1H NMR (300 MHz, CDCl3): d = 3.91 (d, J = 1.0 Hz, 2 H, CH2),
4.01 (d, J = 0.8 Hz, 2 H, CH2), 4.70 (s, 2 H, CH2), 4.79 (s, 2 H, CH2),
5.00 (d, J = 1.3 Hz, 2 H, CH2), 5.16 (d, J = 1.7 Hz, 2 H, CH2), 6.79
(s, 1 H, =CH), 6.89 (s, 1 H, =CH), 7.01–7.03 (m, 1 H, ArH), 7.19
(d, J = 6.8 Hz, 2 H, ArH), 7.28–7.45 (m, 17 H, ArH).
MS (ES+): m/z = 372.2 [M+ + 1].
Anal. Calcd for C18H15Cl2N5: C, 58.08; H, 4.06; N, 18.81. Found:
C, 58.23; H, 4.19; N, 18.69.
13C NMR (50 MHz, CDCl3): d = 45.3, 45.5, 50.4, 51.9, 54.0, 54.1,
123.7, 124.0, 128.17, 128.22, 128.3, 128.5, 128.6, 128.7, 128.8,
128.9, 129.0, 131.7, 131.9, 134.85, 134.90, 135.6, 155.6.
(E)-4-Benzyl-6-(2,6-dichlorobenzylidene)-4,5,6,7-tetrahydro-
tetrazolo[1,5-a]pyrimidine [(E)-23h]
White solid; yield: 0.65 g (93%); mp 150–151 °C; Rf = 0.35
(EtOAc–hexanes, 1:1).
MS (ES+): m/z = 304.2 [M+ + 1].
IR (KBr): 1621 cm–1 (C=N).
Anal. Calcd for C18H17N5: C, 71.27; H, 5.65; N, 23.09. Found: C,
71.14; H, 5.34; N, 23.14.
1H NMR (300 MHz, CDCl3): d = 3.96 (s, 2 H, CH2), 4.72 (d, J = 1.5
Hz, 2 H, CH2), 4.82 (s, 2 H, CH2), 6.58 (s, 1 H, =CH), 7.22–7.30 (m,
1 H, ArH), 7.34–7.38 (m, 7 H, ArH).
13C NMR (50 MHz, CDCl3): d = 46.1, 51.2, 54.3, 126.4, 128.5,
128.6, 128.7, 128.8, 129.3, 130.6, 132.5, 135.0, 135.8, 155.7.
MS (ES+): m/z = 372.2 [M+ + 1].
DART-HRMS (ESI+): m/z [M + H]+ calcd for C18H16Cl2N5:
(E/Z)-4-Benzyl-6-(4-fluorobenzylidene)-4,5,5,6-tetrahydrotet-
razolo[1,5-a]pyrimidine [(E/Z)-23e]
Brown oil; yield: 0.53 g (88%); ratio of diastereomers 5:4; Rf = 0.19
(EtOAc–hexanes, 1:1).
IR (neat): 1620 cm–1 (C=N).
1H NMR (300 MHz, CDCl3): d = 3.88 (s, 2 H, CH2), 3.92 (d, J = 0.9
Hz, 2 H, CH2), 4.69 (s, 2 H, CH2), 4.78 (s, 2 H, CH2), 5.00 (s, 2 H,
CH2), 5.02 (d, J = 1.3 Hz, 2 H, ArH), 6.72 (s, 1 H, =CH), 6.80 (s, 1
H, =CH), 6.88 (t, J = 7.4 Hz, 1 H, ArH), 6.98–7.18 (m, 5 H, ArH),
7.29–7.40 (m, 12 H, ArH).
372.07828; found: 372.07608.
(E/Z)-6-Benzylidene-4-propyl-4,5,6,7-tetrahydrotetrazolo[1,5-
a]pyrimidine [(E/Z)-24a]
Brown oil; yield: 0.65 g (86%); ratio of diastereomers 2:1; Rf = 0.23
13C NMR (50 MHz, CDCl3): d = 45.8, 46.0, 50.4, 51.9, 54.2. 54.3,
116.2, 116.3, 122.6, 122.8, 124.5, 124.7, 124.8, 125.0, 126.4, 126.5,
128.4, 128.5, 128.7, 129.0, 129.2, 130.5, 130.8, 130.9, 135.7, 155.5,
155.7, 158.8, 158.9, 161.3, 161.4.
(EtOAc–hexanes, 1:1).
IR (neat): 1665 cm–1 (C=N).
1H NMR (300 MHz, CDCl3): d = 0.88 (t, J = 7.4 Hz, 3 H, CH3),
0.99 (t, J = 7.4 Hz, 3 H, CH3), 1.61–1.79 (m, 4 H, 2 CH2), 3.43 (t,
J = 7.5 Hz, 2 H, CH2), 3.52 (t, J = 7.5 Hz, 2 H, CH2), 4.03 (d, J = 0.7
Hz, 2 H, CH2), 4.13 (s, 2 H, CH2), 4.99 (d, J = 1.3 Hz, 2 H, CH2),
5.13 (d, J = 1.6 Hz, 2 H, CH2), 6.87 (s, 1 H, =CH), 6.91 (s, 1 H,
=CH), 7.21 (d, J = 7.1 Hz, 4 H, ArH), 7.34–7.44 (m, 6 H, ArH).
MS (ES+): m/z = 322.3 [M+ + 1].
Anal. Calcd for C18H16FN5: C, 67.28; H, 5.02; N, 21.79. Found: C,
67.60; H, 4.79; N, 21.82.
Synthesis 2010, No. 16, 2731–2748 © Thieme Stuttgart · New York

PAPER
Fused Triazoles and Tetrazoles via Intramolecular Cycloaddition
2745
13C NMR (75 MHz, CDCl3): d = 11.0, 11.2, 20.1, 20.2, 45.3, 46.0,
50.0, 52.0, 52.1, 52.6, 123.7, 128.2, 128.4, 128.6, 128.7, 128.8,
131.3, 131.6, 134.7, 135.0.
Anal. Calcd for C14H15Cl2N5: C, 51.86; H, 4.66; N, 21.60. Found:
C, 51.92; H, 4.43; N, 21.73.
(E)-6-(2,6-Dichlorobenzylidene)-4-propyl-4,5,6,7-tetrahydro-
tetrazolo[1,5-a]pyrimidine [(E)-24h]
Brown oil; yield: 0.64 g (85%); Rf = 0.30 (EtOAc–hexanes, 1:4).
IR (neat): 1624 cm–1 (C=N).
MS (ES+): m/z = 256.2 [M+ + 1].
Anal. Calcd for C14H17N5: C, 65.86; H, 6.71; N, 27.43. Found: C,
65.99; H, 6.81; N, 27.24.
(E/Z)-6-(4-Fluorobenzylidene)-4-propyl-4,5,6,7-tetrahydrotet-
razolo[1,5-a]pyrimidine [(E/Z)-24e]
Brown oil; yield: 0.73 g (86%); ratio of diastereomers 2:1; Rf = 0.30
(EtOAc–hexanes, 1:1).
1H NMR (300 MHz, CDCl3): d = 1.00 (t, J = 7.4 Hz, 3 H, CH3),
1.73–1.80 (m, 2 H, CH2), 3.57 (t, J = 7.7 Hz, 2 H, CH2), 4.10 (s, 2
H, CH2), 4.72 (s, 2 H, CH2), 6.67 (s, 1 H, =CH), 7.29 (s, 1 H, ArH),
7.38 (d, J = 8.4 Hz, 2 H, ArH).
IR (neat): 1664 cm–1 (C=N).
13C NMR (75 MHz, CDCl3): d = 11.1, 20.2, 45.6, 51.7, 52.0, 125.6,
128.3, 130.1, 130.2, 132.1, 134.7, 155.1.
1H NMR (300 MHz, CDCl3): d = 0.88 (t, J = 7.4 Hz, 3 H, CH3),
0.98 (t, J = 7.4 Hz, 3 H, CH3), 1.61–1.77 (m, 4 H, 2 CH2), 3.43 (t,
J = 7.6 Hz, 2 H, CH2), 3.51 (t, J = 7.5 Hz, 2 H, CH2), 4.02 (d, J = 0.6
Hz, 2 H, CH2), 4.09 (d, J = 0.7 Hz, 2 H, CH2), 4.98 (d, J = 1.2 Hz,
2 H, CH2), 5.10 (d, J = 1.5 Hz, 2 H, CH2), 6.83 (s, 1 H, =CH), 6.87
(s, 1 H, =CH), 7.07–7.21 (m, 8 H, ArH).
13C NMR (75 MHz, CDCl3): d = 11.0, 11.1, 11.2, 20.1, 20.2, 20.9,
45.2, 45.9, 52.0, 52.1, 52.5, 115.5, 115.7, 115.8, 115.9, 116.0,
116.2, 117.9, 123.8, 127.6, 127.7, 130.2, 130.4, 130.46, 130.51,
130.6, 130.8, 131.0, 164.1.
MS (ES+): m/z = 324.2 [M+ + 1].
Anal. Calcd for C14H15Cl2N5: C, 51.86; H, 4.66; N, 21.60. Found:
C, 51.90; H, 4.50; N, 21.48.
(E)-6-Benzylidene-4-tosyl-4,5,6,7-tetrahydrotetrazolo[1,5-a]py-
rimidine [(E)-30a]
White solid; yield: 0.49 g (82%); mp 156–157 °C; Rf = 0.24
(EtOAc–hexanes, 3:7).
IR (KBr): 1665 cm–1 (C=N).
MS (ES+): m/z = 274.2 [M+ + 1].
1H NMR (300 MHz, CDCl3): d = 2.43 (s, 3 H, CH3), 4.61 (s, 2 H,
CH2), 5.16 (d, J = 1.5 Hz, 2 H, CH2), 7.03 (s, 1 H, =CH), 7.18 (d,
J = 6.4 Hz, 2 H, ArH), 7.30–7.43 (m, 5 H, ArH), 8.04 (d, J = 8.3 Hz,
2 H, ArH).
Anal. Calcd for C14H16FN5: C, 61.52; H, 5.90; N, 25.62. Found: C,
61.43; H, 5.94; N, 25.46.
(E/Z)-6-(4-Methylbenzylidene)-4-propyl-4,5,6,7-tetrahydrotet-
razolo[1,5-a]pyrimidine [(E/Z)-24f]
Brown oil; yield: 0.64 g (84%); ratio of diastereomers 10:7;
13C NMR (75 MHz, CDCl3): d = 21.8, 46.4, 52.0, 121.1, 126.6,
128.7, 128.8, 129.07, 129.10, 129.8, 130.1, 134.5, 145.8.
MS (ES+): m/z = 368.2 [M+ + 1].
Rf = 0.32 (EtOAc–hexanes, 1:1).
IR (neat): 1619 cm–1 (C=N).
Anal. Calcd for C18H17N5O2S: C, 58.84; H, 4.66; N, 19.06. Found:
C, 58.95; H, 4.74; N, 18.84.
1H NMR (300 MHz, CDCl3): d = 0.89 (t, J = 7.4 Hz, 3 H, CH3),
0.99 (t, J = 7.4 Hz, 3 H, CH3), 1.55–1.78 (m, 4 H, 2 CH2), 2.38 (s, 3
H, CH3), 2.39 (s, 3 H, CH3), 3.44 (t, J = 7.6 Hz, 2 H, CH2), 3.49–
3.54 (m, 2 H, CH2), 4.02 (s, 2 H, CH2), 4.13 (s, 2 H, CH2), 4.97 (d,
J = 1.3 Hz, 2 H, CH2), 5.14 (d, J = 1.6 Hz, 2 H, CH2), 6.83 (s, 1 H,
=CH), 6.87 (s, 1 H, =CH), 7.10 (d, J = 8.0 Hz, 4 H, ArH), 7.16–7.23
(m, 4 H, ArH).
(E/Z)-6-(4-Fluorobenzylidene)-4-tosyl-4,5,6,7-tetrahydrotet-
razolo[1,5-a]pyrimidine [(E/Z)-30e]
Brown oil; yield: 0.19 g (76%); ratio of diastereomers 10:7;
Rf = 0.21 (EtOAc–hexanes, 3:7).
IR (neat): 1664 cm–1 (C=N).
1H NMR (300 MHz, CDCl3): d = 2.43 (s, 3 H, CH3), 2.44 (s, 3 H,
CH3), 4.60 (s, 2 H, CH2), 4.76 (s, 2 H, CH2), 5.14 (d, J = 1.3 Hz, 2
H, CH2), 5.30 (s, 2 H, CH2), 7.00 (s, 2 H, 2 =CH), 7.09–7.20 (m, 6
H, ArH), 7.26–7.36 (m, 6 H, ArH), 7.82 (d, J = 8.3 Hz, 2 H, ArH),
8.04 (d, J = 8.3 Hz, 2 H, ArH).
13C NMR (50 MHz, CDCl3): d = 30.1, 46.6, 52.2, 116.3, 116.8,
128.4, 129.0, 130.4, 130.8, 131.0, 133.7.
13C NMR (75 MHz, CDCl3): d = 11.0, 11.2, 20.1, 20.2, 29.1, 29.3,
45.3, 46.1, 50.0, 52.0, 52.1, 52.6, 123.0, 123.4, 128.6, 128.7,
129.39, 129.44, 131.1, 131.4, 131.9, 132.1, 138.2, 138.4.
MS (ES+): m/z = 270.2 [M+ + 1].
DART-HRMS (ESI+): m/z [M + H]+ calcd for C15H20N5: 270.17187;
found: 270.17281.
MS (ES+): m/z = 386.2 [M+ + 1].
(E/Z)-6-(2,4-Dichlorobenzylidene)-4-propyl-4,5,6,7-tetrahydro-
tetrazolo[1,5-a]pyrimidine [(E/Z)-24g]
Brown oil; yield: 0.50 g (83%); ratio of diastereomers 5:3; Rf = 0.23
(EtOAc–hexanes, 1:1).
Anal. Calcd for C18H16FN5O2S: C, 56.09; H, 4.18; N, 18.17. Found:
C, 55.89; H, 4.27; N, 18.25.
IR (neat): 1617 cm–1 (C=N).
(E)-6-(4-Methylbenzylidene)-4-tosyl-4,5,6,7-tetrahydrotetrazo-
lo[1,5-a]pyrimidine [(E)-30f]
Brown oil; yield: 0.39 g (78%); Rf = 0.23 (EtOAc–hexanes, 3:7).
IR (neat): 1666 cm–1 (C=N).
1H NMR (200 MHz, CDCl3): d = 2.38 (s, 3 H, CH3), 2.42 (s, 3 H,
CH3), 4.59 (s, 2 H, CH2), 5.16 (s, 2 H, CH2), 6.99 (s, 1 H, =CH),
7.05–7.09 (m, 2 H, ArH), 7.21–7.36 (m, 2 H, ArH), 7.45–7.52 (m,
2 H ArH), 8.02–8.13 (m, 2 H, ArH).
1H NMR (300 MHz, CDCl3): d = 0.90 (t, J = 7.4 Hz, 3 H, CH3),
0.99 (t, J = 7.4 Hz, 3 H, CH3), 1.58–1.66 (m, 2 H, CH2), 1.72–1.79
(m, 2 H, CH2), 3.44 (t, J = 7.6 Hz, 2 H, CH2), 3.55 (t, J = 7.5 Hz, 2
H, CH2), 3.95 (d, J = 0.6 Hz, 2 H, CH2), 4.07 (d, J = 0.8 Hz, 2 H,
CH2), 4.97 (d, J = 1.6 Hz, 2 H, CH2), 5.04 (d, J = 1.3 Hz, 2 H, CH2),
6.87 (s, 2 H, 2 =CH), 7.11 (d, J = 8.3 Hz, 2 H, ArH), 7.31 (dd,
J1 = 8.3 Hz, J2 = 1.9 Hz, 2 H, ArH), 7.49 (t, J = 2.2 Hz, 2 H, ArH).
13C NMR (50 MHz, CDCl3): d = 11.3, 11.4, 20.4, 20.5, 45.5, 46.6,
50.0, 52.3, 52.4, 52.5, 126.8, 127.0, 127.6, 127.9, 130.1, 130.2,
130.9, 131.3, 131.9, 132.2, 134.9, 135.3, 135.5, 155.2, 155.4.
13C NMR (75 MHz, CDCl3): d = 21.7, 29.7, 47.0, 51.9, 62.0, 123.0,
128.5, 128.6, 129.6, 130.0, 130.1, 139.2.
MS (ES+): m/z = 382.2 [M+ + 1].
MS (ES+): m/z = 324.2 [M+ + 1].
Synthesis 2010, No. 16, 2731–2748 © Thieme Stuttgart · New York

2746
A. Mishra et al.
PAPER
Anal. Calcd for C19H19N5O2S: C, 59.82; H, 5.02; N, 18.36. Found:
C, 59.89; H, 5.13; N, 18.30.
IR (neat): 2101 (N3), 3415 cm–1 (NH).
1H NMR (200 MHz, CDCl3): d = 2.45 (s, 6 H, 2 CH3), 3.74 (d,
J = 6.0 Hz, 2 H, CH2), 3.79 (d, J = 6.4 Hz, 2 H, CH2), 3.96 (d,
J = 5.0 Hz, 4 H, 2 CH2), 4.73 (t, J = 5.8 Hz, 1 H, NH), 4.82 (t,
J = 6.2 Hz, 1 H, NH), 6.63 (s, 1 H, =CH), 6.65 (s, 1 H, =CH), 6.96–
7.16 (m, 9 H, ArH), 7.28–7.35 (m, 3 H, ArH), 7.68 (d, J = 8.3 Hz, 2
H, ArH), 7.80 (d, J = 8.3 Hz, 2 H, ArH).
13C NMR (50 MHz, CDCl3): d = 21.9, 42.1, 48.3, 49.3, 56.3, 115.7,
116.1, 127.6, 130.2, 130.7, 130.9, 131.7, 132.4, 132.8, 137.4, 144.3.
MS (ES+): m/z = 361.1 [M+ + 1].
(E/Z)-6-(2,4-Dichlorobenzylidene)-4-tosyl-4,5,6,7-tetrahydro-
tetrazolo[1,5-a]pyrimidine [(E/Z)-30g]
White solid; yield: 0.46 g (84%); ratio of diastereomers 5:2; mp
158–159 °C; Rf = 0.22 (EtOAc–hexanes, 3:7).
IR (KBr): 1663 cm–1 (C=N).
1H NMR (200 MHz, CDCl3): d = 2.42 (s, 6 H, 2 CH3), 4.57 (s, 2 H,
CH2), 4.67 (s, 2 H, CH2), 4.99 (s, 2 H, CH2), 5.07 (s, 2 H, CH2), 6.95
(s, 1 H, =CH), 7.04 (s, 2 H, =CH, ArH), 7.27–7.36 (m, 7 H, ArH),
7.50 (s, 2 H, ArH), 7.91 (d, J = 6.6 Hz, 2 H, ArH), 8.03 (d, J = 7.3
Hz, 2 H, ArH).
Anal. Calcd for C17H17FN4O2S: C, 56.65; H, 4.75; N, 15.55. Found:
C, 56.95; H, 4.59; N, 15.57.
13C NMR (50 MHz, CDCl3): d = 22.1, 46.2, 46.6, 51.9, 124.3,
127.9, 128.2, 128.8, 128.9, 130.4, 130.5, 130.7, 130.8, 131.2, 131.6,
134.2, 135.0, 136.2, 146.3.
(E/Z)-2-(Azidomethyl)-3-(4-methylphenyl)-N-tosylprop-2-en-1-
amine [(E/Z)-28f]
Colorless oil; yield: 1.00 g (50%); ratio of diastereomers 2:1;
Rf = 0.21 (EtOAc–hexanes, 1:4).
MS (ES+): m/z = 436.0 [M+ + 1].
HRMS (EI): m/z [M]+ for C18H16Cl2N5O2S: 435.0324; found:
IR (neat): 2102 (N3), 3458 cm–1 (NH).
435.0329.
1H NMR (300 MHz, CDCl3): d = 2.31 (s, 3 H, CH3), 2.34 (s, 3 H,
CH3), 2.43 (s, 3 H, CH3), 2.44 (s, 3 H, CH3), 3.77 (d, J = 6.2 Hz, 2
H, CH2), 3.92–3.96 (m, 2 H, CH2), 4.08 (d, J = 6.1 Hz, 4 H, 2 CH2),
4.63 (t, J = 5.8 Hz, 1 H, NH), 4.74 (t, J = 6.2 Hz, 1 H, NH), 6.62 (s,
1 H, =CH), 6.64 (s, 1 H, =CH), 6.97–7.03 (m, 3 H, ArH), 7.08–7.16
(m, 4 H, ArH), 7.26–7.33 (m, 4 H, ArH), 7.67 (d, J = 8.1 Hz, 2 H,
ArH), 7.75–7.80 (m, 3 H, ArH).
13C NMR (50 MHz, CDCl3): d = 21.6, 21.9, 42.3, 47.5, 48.5, 56.4,
127.6, 128.3, 129.0, 129.58, 129.61, 129.8, 130.15, 130.21, 133.6,
134.0, 144.1.
(E/Z)-2-(Azidomethyl)-3-bromo-1-phenylprop-2-ene
[(E/Z)-27a]; Typical Procedure for 27a,e–g
To a stirred soln of 3a (1.00 g, 5.29 mmol) in anhyd CH2Cl2 (20 mL)
was added dropwise a soln of PBr3 (1.71 mL, 6.35 mmol) in CH2Cl2
(15 mL) at 0 °C and the mixture was stirred at r.t. for 30 min. When
the reaction was complete, it was quenched with ice water (30 mL)
and partitioned in a separating funnel. The organic layer was col-
lected and the aqueous layer was extracted with CHCl3 (2 × 20 mL).
The organic layers were combined, washed with brine (50 mL),
dried (anhyd Na2SO4), and concentrated to afford the crude product,
which was purified by column chromatography (silica gel, 100–200
mesh, EtOAc–hexanes, 1:19) to yield pure 27a (1.06 g, 80%) as a
brown oil.
MS (ES+): m/z = 357.1 [M+ + 1].
Anal. Calcd for C18H20N4O2S: C, 60.65; H, 5.66; N, 15.72. Found:
C, 60.52; H, 5.84; N, 15.81.
(E)-2-(Azidomethyl)-3-(2,4-dichlorophenyl)-N-tosylprop-2-en-
1-amine [(E)-28g]
Colorless viscous oil; yield: 0.75 g (45%); Rf = 0.23 (EtOAc–
(E/Z)-2-(Azidomethyl)-3-phenyl-N-tosylprop-2-en-1-amine
[(E/Z)-28a]; Typical Procedure for 28a,e–g
To a stirred soln of 27a (1.50 g, 5.95 mmol) in anhyd DMF (10 mL)
was added NaH (0.24 g, 5.95 mmol, 60% in oil). After 5 min,
TsNH2 (1.12 g, 6.55 mmol) was added and mixture stirred at r.t. for
2 h. When the reaction was complete, the mixture was diluted with
H2O (30 mL) and extracted with EtOAc (30 mL). The aqueous layer
was separated and extracted with EtOAc (3 × 20 mL). The com-
bined organic layers were dried (anhyd Na2SO4) and concentrated
to obtain the crude product, which was purified by column chroma-
tography (silica gel, 100–200 mesh, EtOAc–hexanes, 1:4) to furnish
(E/Z)-28a (1.00 g, 49%) as a colorless oil; ratio of diastereomers
10:7; Rf = 0.23 (EtOAc–hexanes, 1:4).
hexanes, 1:4).
IR (neat): 2102 (N3), 3292 cm–1 (NH).
1H NMR (200 MHz, CDCl3): d = 2.43 (s, 3 H, CH3), 2.88 (s, 2 H,
CH2), 2.95 (s, 2 H, CH2), 4.97 (t, J = 6.3 Hz, 1 H, NH), 6.60 (s, 1 H,
=CH), 7.02 (d, J = 8.1 Hz, 1 H, ArH), 7.21–7.40 (m, 4 H, ArH), 7.79
(d, J = 7.7 Hz, 1 H, ArH), 8.01 (s, 1 H, ArH).
13C NMR (50 MHz, CDCl3): d = 21.9, 50.2, 53.1, 126.9, 127.7,
129.0, 129.5, 129.7, 130.0, 130.7, 132.9, 133.1, 138.3, 138.6, 145.6.
MS (ES+): m/z = 411.1 [M+ + 1].
IR (neat): 2100 (N3), 3424 cm–1 (NH).
Anal. Calcd for C17H16Cl2N4O2S: C, 49.64; H, 3.92; N, 13.62.
Found: C, 49.75; H, 3.83; N, 13.80.
1H NMR (300 MHz, CDCl3): d = 2.45 (s, 6 H, 2 CH3), 3.78–3.82
(m, 4 H, 2 CH2), 3.98 (s, 4 H, 2 CH2), 4.66 (t, J = 6.0 Hz, 1 H, NH),
4.77 (t, J = 6.1 Hz, 1 H, NH), 6.68 (s, 1 H, =CH), 6.70 (s, 1 H, =CH),
7.09–7.16 (m, 4 H, ArH), 7.28–7.38 (m, 10 H, ArH), 7.68 (d, J = 8.3
Hz, 2 H, ArH), 7.81 (d, J = 8.3 Hz, 2 H, ArH).
13C NMR (50 MHz, CDCl3): d = 21.6, 21.9, 42.3, 47.5, 48.5, 56.4,
127.6, 128.3, 129.0, 129.6, 129.8, 130.2, 133.6, 134.0,,144.1.
(E/Z)-N-[2-(Azidomethyl)-3-phenylprop-2-enyl]-N-tosylcyan-
amide [(E/Z)-29a]; Typical Procedure for 29a,e–g
To a stirred soln of (E/Z)-28a (0.70 g, 2.05 mmol) in anhyd CH2Cl2
(20 mL) was added NaH (0.16 g, 4.09 mmol, 60% in oil). After 5
min, CNBr (0.28 g, 2.67 mmol) was added and mixture was stirred
at r.t. for 2 h. When the reaction was complete, CH2Cl2 was re-
moved from the mixture and the residue was diluted with EtOAc
(30 mL) and H2O (30 mL). The aqueous layer was separated and ex-
tracted with EtOAc (3 × 20 mL). The combined organic layers were
dried (Na2SO4) and then concentrated to obtain the crude product,
which was purified by column chromatography (silica gel, 100–200
mesh, EtOAc–hexanes, 3:7) to yield (E/Z)-29a (0.56 g, 75%) as a
colorless oil; ratio of diastereomers 10:7; Rf = 0.24 (EtOAc–
hexanes, 1:4).
MS (ES+): m/z = 343.1 [M+ + 1].
Anal. Calcd for C17H18N4O2S: C, 59.63; H, 5.30; N, 16.36. Found:
C, 59.69; H, 5.41; N, 16.27.
(E/Z)-2-(Azidomethyl)-3-(4-fluorophenyl)-N-tosylprop-2-en-1-
amine [(E/Z)-28e]
Colorless oil; yield: 0.40 g (60%); ratio of diastereomers 1:1;
Rf = 0.25 (EtOAc–hexanes, 1:4).
IR (neat): 2103 (N3), 2230 cm–1 (CN).
Synthesis 2010, No. 16, 2731–2748 © Thieme Stuttgart · New York

PAPER
Fused Triazoles and Tetrazoles via Intramolecular Cycloaddition
2747
1H NMR (300 MHz, CDCl3): d = 2.49 (s, 6 H, 2 CH3), 3.93 (s, 2 H,
CH2), 3.98 (s, 2 H, CH2), 4.19 (s, 4 H, 2 CH2), 6.81 (s, 1 H, =CH),
6.98 (s, 1 H, =CH), 7.16–7.19 (m, 4 H, ArH), 7.27–7.45 (m, 10 H,
ArH), 7.78 (dd, J1 = 8.5 Hz, J2 = 2.1 Hz, 2 H, ArH), 7.90 (dd,
J1 = 8.2 Hz, J2 = 2.0 Hz, 2 H, ArH).
13C NMR (50 MHz, CDCl3): d = 21.9, 47.9, 38.2, 54.4, 54.5, 108.4,
127.6, 127.9, 128.08, 128.13, 128.4, 128.6, 128.7, 128.8, 128.9,
130.6, 130.7, 133.7, 134.5, 138.0, 138.1, 146.9.
Anal. Calcd for C18H15Cl2N5O2S: C, 49.55; H, 3.47; N, 16.05.
Found: C, 49.43; H, 3.65; N, 16.12.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
Acknowledgment
MS (ES+): m/z = 368.2 [M+ + 1].
Four of the authors (A.M., S.H., S.B., and N.R.) gratefully acknow-
ledge the financial support from CSIR, New Delhi. Authors grate-
fully acknowledge SAIF Division of CDRI for providing the
spectroscopic data. This work was funded by a grant from DST,
New Delhi.
Anal. Calcd for C18H17N5O2S: C, 58.84; H, 4.66; N, 19.06. Found:
C, 59.06; H, 4.93; N, 18.73.
(E/Z)-N-[2-(Azidomethyl)-3-(4-fluorophenyl)prop-2-enyl]-N-
tosylcyanamide [(E/Z)-29e]
Colorless oil; yield: 0.30 g (77%); ratio of diastereomers 1:1;
Rf = 0.27 (EtOAc–hexanes, 1:4).
References
IR (neat): 2103 (N3), 2229 cm–1 (CN).
(1) This is CDRI communication No. 7938.
1H NMR (200 MHz, CDCl3): d = 2.50 (s, 6 H, 2 CH3), 3.94 (d,
J = 6.6 Hz, 4 H, 2 CH2), 4.15 (d, J = 6.3 Hz, 4 H, 2 CH2), 6.76 (s, 1
H, =CH), 6.94 (s, 1 H, =CH), 7.00–7.20 (m, 8 H, ArH), 7.42 (t,
J = 7.3 Hz, 4 H, ArH), 7.79 (d, J = 7.9 Hz, 2 H, ArH), 7.89 (d,
J = 8.0 Hz, 2 H, ArH).
13C NMR (50 MHz, CDCl3): d = 22.2, 48.0, 48.4, 54.7, 54.8, 115.9,
116.4, 128.2, 128.37, 128.41, 130.7, 130.9, 131.0, 131.1, 133.4,
134.0, 137.2, 137.3, 147.2, 147.3, 165.4.
(2) See, for example: (a) El-Sagheer, A. H.; Brown, T. J. Am.
Chem. Soc. 2009, 131, 3958. (b) Maltzahn, G. V.; Ren, Y.;
Park, J. H.; Min, D. H.; Kotamraju, V. R.; Jayakumar, J.;
Fogal, V.; Sailor, M. J.; Ruoslahti, E.; Bhatia, S. N.
Bioconjugate Chem. 2008, 19, 1570. (c) Moses, J. E.;
Moorhouse, A. D. Chem. Soc. Rev. 2007, 36, 1249; and
references cited therein. (d) Lutz, J.-F.; Zarafshani, Z. Adv.
Drug Delivery Rev. 2008, 60, 958; and references cited
therein. (e) Galibert, M.; Dumy, P.; Boturyn, D. Angew.
Chem. Int. Ed. 2009, 48, 2576.
MS (ES+): m/z = 386.0 [M+ + 1].
(3) See, for example: (a) Hansen, T. S.; Daugaard, A. E.;
Hvilsted, S.; Larsen, N. B. Adv. Mater. (Weinheim, Ger.)
2009, 21, 4483. (b) Nandivada, H.; Jiang, X. W.; Lahann, J.
Adv. Mater. (Weinheim, Ger.) 2007, 19, 2197. (c) Wu, P.;
Feldman, A. K.; Nugent, A. K.; Hawker, C. J.; Scheel, A.;
Voit, B.; Pyun, J.; Fréchet, J. M. J.; Sharpless, K. B.; Fokin,
V. V. Angew. Chem. Int. Ed. 2004, 43, 3928. (d) Aucagne,
V.; Hanni, K. D.; Leigh, D. A.; Lusby, P. J.; Walker, D. B.
J. Am. Chem. Soc. 2006, 128, 2186. (e) Ye, C. F.; Gard, G.
L.; Winter, R. W.; Syvret, R. G.; Twamley, B.; Shreeve, J.
M. Org. Lett. 2007, 9, 3841.
(4) Representative citations: (a) Kolb, H. C.; Sharpless, K. B.
Drug Discovery Today 2003, 8, 1128. (b) Maurya, S. K.;
Gollapalli, D. R.; Kirubakaran, S.; Zhang, M.; Johnson, C.
R.; Benjamin, N. N.; Hedstrom, L.; Cuny, G. D. J. Med.
Chem. 2009, 52, 4623. (c) Puig-Basagoiti, F.; Qing, M.;
Dong, H.; Zhang, B.; Zou, G.; Yuan, Z.; Shi, P.-Y. Antiviral
Res. 2009, 83, 71. (d) Mohapatra, D. K.; Maity, P. K.;
Shabab, M.; Khan, M. I. Bioorg. Med. Chem. Lett. 2009, 19,
5241. (e) Gill, C.; Jadhav, G.; Shaikh, M.; Kale, R.;
Ghawalkar, A.; Nagargoje, D.; Shiradkar, M. Bioorg. Med.
Chem. Lett. 2008, 18, 6244. (f) Aufort, M.; Herscovici, J.;
Bouhours, P.; Moreau, N.; Girard, C. Bioorg. Med. Chem.
Lett. 2008, 18, 1195. (g) Al-Masoudim, N. A.; Al-Soud, Y.
A. Tetrahedron Lett. 2002, 43, 4021. (h) Brockunier, L. L.;
Parmee, E. R.; Ok, H. O.; Candelore, M. R.; Cascieri, M. A.;
Colwell, L. F.; Deng, L.; Feeney, W. P.; Forrest, M. J.; Hom,
G. J.; MacIntyre, D. E.; Tota, L.; Wyvratt, M. J.; Fisher, M.
H.; Weber, A. E. Bioorg. Med. Chem. Lett. 2000, 10, 2111.
(i) Alvarez, R.; Velazquez, S.; San, F.; Aquaro, S.; De, C.;
Perno, C. F.; Karlsson, A.; Balzarini, J.; Camarasa, M. J.
J. Med. Chem. 1994, 37, 4185. (j) Genin, M. J.; Allwine, D.
A.; Anderson, D. J.; Barbachyn, M. R.; Emmert, D. E.;
Garmon, S. A.; Graber, D. R.; Grega, K. C.; Hester, J. B.;
Hutchinson, D. K.; Morris, J.; Reischer, R. J.; Ford, C. W.;
Zurenko, G. E.; Hamel, J. C.; Schaadt, R. D.; Stapert, D.;
Yagi, B. H. J. Med. Chem. 2000, 43, 953.
Anal. Calcd for C18H16FN5O2S: C, 56.09; H, 4.18; N, 18.17. Found:
C, 56.15; H, 4.25; N, 18.02.
(E/Z)-N-[2-(Azidomethyl)-3-(4-methylphenyl)prop-2-enyl]-N-
tosylcyanamide [(E/Z)-29f]
Colorless oil; yield: 0.56 g (80%); ratio of diastereomers 1:1;
Rf = 0.28 (EtOAc–hexanes, 1:4).
IR (neat): 2101 (N3), 2228 cm–1 (CN).
1H NMR (200 MHz, CDCl3): d = 2.34 (s, 6 H, 2 CH3), 2.48 (s, 6 H,
2 CH3), 3.90 (s, 2 H, CH2), 3.98 (s, 2 H, CH2), 4.20 (s, 2 H, CH2),
4.49 (s, 2 H, CH2), 6.77 (s, 1 H, =CH), 6.94 (s, 1 H, =CH), 7.02–
7.45 (m, 12 H, ArH), 7.77–7.91 (m, 4 H, ArH).
13C NMR (50 MHz, CDCl3): d = 21.2, 21.78, 21.82, 47.8, 48.1,
54.0, 54.5, 54.6, 126.9, 127.9, 128.0, 128.6, 128.8, 128.9, 129.0,
129.3, 129.4, 129.7, 130.4, 130.5, 133.6, 133.9, 138.1, 138.2, 138.6,
139.4.
MS (ES+): m/z = 382.0 [M+ + 1].
Anal. Calcd for C19H19N5O2S: C, 59.82; H, 5.02; N, 18.36. Found:
C, 59.73; H, 5.06; N, 18.30.
(E)-N-[2-(Azidomethyl)-3-(2,4-dichlorophenyl)prop-2-enyl]-N-
tosylcyanamide [(E)-29g]
Colorless oil; yield: 0.60 g (90%); Rf = 0.30 (EtOAc–hexanes, 1:4).
IR (neat): 2101 (N3), 2228 cm–1 (CN).
1H NMR (300 MHz, CDCl3): d = 2.49 (s, 3 H, CH3), 3.89 (s, 2 H,
CH2), 4.21 (s, 2 H, CH2), 6.74 (s, 1 H, =CH), 7.10 (d, J = 8.3 Hz, 1
H, ArH), 7.25–7.26 (m, 1 H, ArH), 7.43–7.46 (m, 3 H, ArH), 7.90
(d, J = 8.4 Hz, 2 H, ArH).
13C NMR (75 MHz, CDCl3): d = 22.2, 48.6, 54.2, 108.5, 127.6,
128.4, 130.1, 130.9, 131.0, 131.6, 131.9, 133.9, 135.0, 135.7, 147.2.
MS (ES+): m/z = 436.0 [M+ + 1].
Synthesis 2010, No. 16, 2731–2748 © Thieme Stuttgart · New York

2748
A. Mishra et al.
PAPER
(8) Patra, A.; Bhaduri, A. P.; Batra, S. Synlett 2002, 1819.
(9) Kim, K. H.; Lee, H. S.; Kim, J. N. Tetrahedron Lett. 2009,
50, 1249.
(5) (a) Huisgen, R.; Guenter, S.; Leander, M. Chem. Ber. 1967,
100, 2494. (b) Huisgen, R. Angew. Chem., Int. Ed. Engl.
1963, 2, 565; Angew. Chem. 1963, 75, 604. (c) Huisgen, R.
J. Org. Chem. 1968, 31, 2291. (d) Huisgen, R. J. Org.
Chem. 1976, 41, 403. (e) Huisgen, R. 1,3-Dipolar
(10) Kim, J. N.; Chung, Y. M.; Im, Y. J. Tetrahedron Lett. 2002,
43, 6209.
Cycloaddition Chemistry; Padwa, A., Ed.; Wiley-
(11) (a) Bajwa, J. S.; Chen, G.-P.; Prasad, K.; Repic, O.;
Blacklock, T. J. Tetrahedron Lett. 2006, 47, 6425. (b) Park,
D. Y.; Lee, M. J.; Kim, T. H.; Kim, J. N. Tetrahedron Lett.
2005, 46, 8799.
Interscience: New York, 1984. (f) Huisgen, R. The
Adventure Playground of Mechanisms and Novel Reactions:
Profiles, Pathways and Dreams; Seeman, J. I., Ed.;
American Chemical Society: Washington DC, 1994.
(6) See, for example: (a) Kolb, H. C.; Finn, M. G.; Sharpless, K.
B. Angew. Chem. Int. Ed. 2001, 40, 2004. (b) Tron, G. C.;
Pirali, T.; Billington, R. A.; Canonico, P. L.; Sorba, G.;
Genazzani, A. A. Med. Res. Rev. 2008, 28, 278; and
references cited therein. (c) Lewis, W. G.; Green, L. G.;
Grynszpan, F.; Radiæ, Z.; Carlier, P. R.; Taylor, P.; Finn, M.
G.; Sharpless, K. B. Angew. Chem. Int. Ed. 2002, 41, 1053.
(d) Kalisiak, J.; Sharpless, K. B.; Fokin, V. V. Org. Lett.
2008, 10, 3171. (e) Becer, C. R.; Hoogenboom, R.;
Schubert, U. S. Angew. Chem. Int. Ed. 2009, 48, 4900.
(f) Brawn, R. A.; Welzel, M.; Lowe, J. T.; Panek, J. S. Org.
Lett. 2010, 12, 336.
(7) (a) Park, S. P.; Ahn, S.-H.; Lee, K.-J. Tetrahedron 2010, 66,
3490. (b) Song, Y. S.; Lee, K. J. J. Heterocycl. Chem. 2006,
43, 1721. (c) Ji, S. H.; Hong, W. P.; Ko, S.-H.; Lee, K. J.
J. Heterocycl. Chem. 2006, 43, 799. (d) Chandrasekhar, S.;
Basu, D.; Rambabu, C. Tetrahedron Lett. 2006, 47, 3059.
(e) Sreedhar, B.; Reddy, P. S.; Kumar, N. S. Tetrahedron
Lett. 2006, 47, 3055. (f) Declerck, V.; Toupet, L.; Martinez,
J.; Lamaty, F. J. Org. Chem. 2009, 74, 2004.
(12) (a) Nag, S.; Mishra, A.; Batra, S. Eur. J. Org. Chem. 2008,
4334. (b) Mishra, A.; Batra, S. Synthesis 2009, 3076.
(13) See, for example: (a) Aldhoun, M.; Massi, A.; Dondoni, A.
J. Org. Chem. 2008, 73, 9565. (b) Kimura, T.; Shuto, D.;
Hamada, Y.; Igawa, N.; Kasai, S.; Liu, P.; Hidaka, K.;
Hamada, T.; Hayashi, Y.; Kiso, Y. Bioorg. Med. Chem. Lett.
2005, 15, 211. (c) Srihari, P.; Dutta, P.; Rao, R. S.; Yadav, J.
S.; Chandrasekhar, S.; Thombare, P.; Mohapatra, J.;
Chatterjee, A.; Jain, M. R. Bioorg. Med. Chem. Lett. 2009,
19, 5569. (d) Nelson, D. W.; Gregg, R. J.; Kort, M. E.;
Medrano, A. P.; Voight, E. A.; Wang, Y.; Grayson, G.;
Namovic, M. T.; Donnelly-Roberts, D. L.; Niforatos, W.;
Honore, P.; Jarvis, M. F.; Faltynek, C. R.; Carroll, W. A.
J. Med. Chem. 2006, 49, 3659.
Synthesis 2010, No. 16, 2731–2748 © Thieme Stuttgart · New York