Synthesis of fused [5,5]-1,2,4-triazoles via tandem thioimidate cyclopropane rearrangement-cyclization

Article abstract of DOI:10.1080/00397910600941414

The synthesis of fused [5,5]-1,2,4-triazoles via a tandem cyclopropane rearrangement-cyclization sequence is described. Optimization of the cyclization reaction was achieved thermally using iPrOH as the solvent in the presence of TEA. This method was appl

Full text of DOI:10.1080/00397910600941414

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Synthesis of Fused [5,5]‐1,2,4‐Triazoles
via Tandem Thioimidate Cyclopropane
Rearrangement–Cyclization
Christina Ng Di Marco a & Scott D. Kuduk a
a Department of Medicinal Chemistry, Merck Research Laboratories, West
Point, Pennsylvania, USA
Version of record first published: 23 Nov 2006.
To cite this article: Christina Ng Di Marco & Scott D. Kuduk (2006): Synthesis of Fused [5,5]‐1,2,4‐Triazoles
via Tandem Thioimidate Cyclopropane Rearrangement–Cyclization, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 36:22, 3377-3386
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Synthetic Communicationsw, 36: 3377–3386, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600941414
Synthesis of Fused [5,5]-1,2,4-Triazoles via
Tandem Thioimidate Cyclopropane
Rearrangement–Cyclization
Christina Ng Di Marco and Scott D. Kuduk
Department of Medicinal Chemistry, Merck Research Laboratories,
West Point, Pennsylvania, USA
Abstract: The synthesis of fused [5,5]-1,2,4-triazoles via a tandem cyclopropane
rearrangement–cyclization sequence is described. Optimization of the cyclization
reaction was achieved thermally using iPrOH as the solvent in the presence of TEA.
This method was applied to the preparation of 3-substituted-7-aryl-pyrrolo-1,2,4-
triazoles in good to excellent yields.
Keywords: Cyclizations, cyclopropane, fused-ring systems, rearrangements, triazoles
The synthesis of fused 1,2,4-triazoles has attracted considerable attention
because of the varied biological activities of these compounds.[1] In connec-
tion with an ongoing synthesis program, we were interested in preparing
fused [5,5]-1,2,4-triazoles. A typical approach to 1,2,4-fused triazoles
involves the condensation of an imino ether or thioether with an acyl
hydrazide to provide an amidrazone intermediate that undergoes cyclodehy-
dration to yield the triazole.[2] Recently, we reported that the thioimidate
cyclopropane rearrangement is an efficient method for the synthesis of 2,3-
diaminodihydropyrroles.[3] As shown in Scheme 1, we envisioned that the
initial product of the rearrangement, S-methyl thioimidate I, could also
serve as a useful intermediate in the preparation of fused [5,5]-1,2,4-
Received in the USA April 27, 2006
Address correspondence to Christina Ng Di Marco, Department of Medicinal
Chemistry, Merck Research Laboratories, WP14-3, Sumneytown Pike, P.O. Box 4,
West Point, Pennsylvania 19486, USA. E-mail: christina_ng@merck.com
3377

3378
C. N. Di Marco and S. D. Kuduk
Scheme 1. Thioimidate cyclopropane rearrangement–cyclization.
triazoles such as II. As such, a tandem rearrangement–cyclization sequence
would represent a viable method for the synthesis of this type of fused
[5,5]-1,2,4-triazole. Herein, we describe the execution of this plan and
report our results to prepare 3-substituted-7-aryl-pyrrolo-1,2,4 triazoles
using this approach.
The methyl iodide–mediated rearrangement of thioamide 1 proceeded
smoothly in acetone at 608C to afford HI salt 2a in essentially quantitative
yield (Scheme 2). The reaction of 2a with benzhydrazide to form triazole
3a was then investigated in various solvents and temperatures. Results
are shown in Table 1.
The condensation of thio-imino ethers with hydrazides to form triazoles
can be capricious and in some cases requires extensive heating in solvents
such as DMF, leading to only moderate isolated yields.[4] Accordingly, we
chose to investigate microwave heating as an approach to improve the rate
and efficiency of this transformation. Initial attempts involved reaction of
HI salt 2a with 1.5 equivalents of the hydrazide in the absence of base.
Reaction progress was monitored by liquid chromatography/mass spec-
trometry (LC/MS). Low yields (ꢀ15%) and multiple side products were
observed when the mixtures were subjected to heating via microwave in
various solvents for 30 min (entries 1–4). For reactions carried out in
N,N-dimethylformamide (DMF), the primary side products 4 and 5 resulted
from hydrolysis and incorporation of a formyl group due to decomposition
of the solvent under the experimental conditions that were employed.
Addition of triethylamine did not improve either the conversion of the
reactions or the purity of the products with microwave heating (entry 5).
Scheme 2. Synthesis of 3,7-diphenyl-pyrrolo-1,2,4-triazole.

Synthesis of Fused [5,5]-1,2,4-Triazoles
3379
Table 1. Optimization of triazole 3a synthesis
Entry Solvent Additive
Temp (8C)
t (h) Conversion (%)a Yield (%)b
1
2
DMSO
EtOH
DMF
—
—
180 (mwave)
180 (mwave)
180 (mwave)
180 (mwave)
180 (mwave)
120
0.5
0.5
0.5
0.5
0.5
3
,5
,5
15
,5
,5
,5
—
—
3
—
—
15
—
4
iPrOH
DMSO
DMF
5
TEA
—
—
—
6
7
DMF
TEA
—
150
120
24
72
,5
.97
,15
.97c
.97
66
—
8
DMSO
DMSO
DMSO
iPrOH
iPrOH
24
72
48
24
3
9
TEA
K2CO3
—
120
120
71
—
10
11
12
180
150
—
.97
TEA
Notes: Reaction conditions: 0.10 M solutions, sealed vials.
aConversion based on LC/MS.
bIsolated yield.
cTotal conversion. Contains mixture of 3a:6:7 (see Scheme 3).
As a consequence of the poor results obtained using microwave tech-
nology, we next evaluated the cyclization under standard thermal conditions.
Employing polar aprotic solvents such as DMF or dimethylsulfoxide
(DMSO) in the absence of base, we again observed poor yields (entries 6,
8). Use of the inorganic base potassium carbonate also led to slow reaction
times and incomplete conversions even after extended reaction times (entry
10). By contrast, addition of triethylamine (2.0 eq.) in DMF or DMSO led
to efficient conversions under these thermal conditions (entries 7, 9) to
provide 3a in 66% isolated yield. As previously described, reactions in
DMF also produced side products 4 and 5, which were not observed when
DMSO was employed as the solvent. Additionally, an increase in overall
reaction yield was obtained with DMSO. Because thermal cyclizations of ami-
drazones have been previously reported in alcohols,[1b,4] the use of isopropa-
nol was examined, and this led to the best conversions and highest product
yields (.97%). The high yield is noteworthy because cyclizations to form
fused [5,5]-1,2,4-triazoles have been reported to proceed in low yields, as a
result of ring strain.[2a,5] It is interesting to note that in the absence of base,

3380
C. N. Di Marco and S. D. Kuduk
Scheme 3. Formation of triazole isomer.
the reaction in isopropanol proceeded slowly and resulted in a mixture of
desired product 3a, uncyclized intermediate 6, and isomer 7 (Scheme 3).
The structure of the unanticipated isomer 7 was determined through the
assignment of proton and carbon chemical shifts from the analysis of
HMQC and HMBC spectra. The two-, three-, and four-bond HMBC corre-
lations and ROEs are consistent with the structure depicted.
We propose that regioisomer 7 is formed as a consequence of the
formation of isopropyl imidate 8 (Scheme 4). (Heating 2 in iPrOH at 1808C
afforded isopropyl imidate 8.) The resultant steric hindrance provided by
the isopropyl group at the 2-position leads to ring-opening of the pyrrolidine
core. The hydrazide preferentially attacks at the 5-position, which is activated
by virtue of the adjacent protonated imine nitrogen. Subsequent condensation
of the hydrazide with the isopropyl imidate in 9, followed by cyclodehydra-
tion, affords isomer 7. This isomer is not observed under basic conditions or
with the nonnucleophilic solvents DMF and DMSO.
Having improved the conditions (iPrOH, TEA, 1508C) for synthesizing
1,2,4-triazoles, we next sought to explore the scope of our protocol for the
preparation of other 3-substituted 1,2,4-triazoles (Table 2). Yields were
notably higher for reactions conducted in iPrOH relative to those observed
in DMSO (Table 2, entries 1–4), which is consistent with the results
obtained with benzhydrazide. The fastest reaction rates were observed with
the least sterically hindered hydrazide 3g. As predicted by its decreased
nucleophilicity, the analog bearing the trifluoromethyl group, 3e, was the
least reactive of the substrates which were examined. Extended reaction
times were required to form products with aromatic hydrazides bearing
pyridyl (3c, d) and phenyl (3a, f, h) substituents. To further expand upon
the diversity of this reaction, various 3-phenyl-pyrrolo-1,2,4-triazole
Scheme 4. Proposed mechanism for formation of triazole isomer.

Synthesis of Fused [5,5]-1,2,4-Triazoles
3381
Table 2. Synthesis of substituted pyrrolo-1,2,4-triazolesa
Entry
Product
R1 ¼
3-Ph
3-Ph
R2 ¼
Ph
t (h)
Yield (%)b
1
2
3a
7
4
.97 (71)
.97 (14)
.97 (54)
87 (37)
52
3b
3c
Me
3
3-Ph
3-Ph
2-pyridyl
3-pyridyl
CF3
24
7
4
3d
3e
5
3-Ph
3-Ph
24
24
2
6
3f
3g
p-OMePh
H
.97
69
7
3-Ph
3-Ph
8
3h
3i
p-NO2Ph
t-Bu
Ph
6
92
9
3-Ph
5-Ph
3
.97
75
10
11
12
13
12a
12b
12c
12d
24
24
24
24
3-(p-OMe-Ph)
5-CO2Bnc
3-NHCBz
Ph
Ph
58
70
Ph
39
aReaction conditions: iPrOH, TEA, 1508C (sealed vial).
bYields in parentheses are for reactions run in DMSO.
cProduct formed is the isopropyl ester from transesterification with solvent.
analogues from other thioimidate cyclopropane rearrangement products (2b–
e, Table 2) were prepared in fair to good yields (12a–d, Table 2).
In summary, an efficient method for the synthesis of fused [5,5]-1,2,4-
triazoles via tandem thioimidate cyclopropane rearrangement–cyclization is
described. The cyclization of the amidrazone intermediate was improved
through the use of iPrOH in the presence of TEA. This versatile approach
was used to prepare a number of 3-substituted-7-aryl-pyrrolo-1,2,4-triazoles
in good to excellent yields.
EXPERIMENTAL
Materials
All reagents were purchased from Aldrich Chemical Company (USA) or
1
Acros Organics (USA). All the solvents used were of analytical grade. H
and 13C (400-MHz) NMR spectra were recorded on a Varian VXR 400 spec-
trometer unless otherwise noted. The chemical shifts are reported in d (ppm)

3382
C. N. Di Marco and S. D. Kuduk
using the d 0.00 signal of Me4Si as an internal standard. High-resolution MS
data were obtained on a Bruker Daltonics FTICR/MS. High pressure liquid
chromatography (HPLC) spectra were recorded on a Hewlett-Packard 1100
with a CombiScreen Pro C-18 column. The purity of compounds were
assessed by analytical HPLC: 1) Linear gradient over 10 min of CH3CN/
0.1% trifluoroacetic acid (TFA) and H2O/0.1% TFA 10:90 to 95:5 and
2 min at 95:5; flow rate 1.0 mL/min, detection at 215 and 254 nm (YMC-
Pack Pro C18, 50 ꢁ 4.6 mm column). 2) Linear gradient over 3.5 min of
CH3CN/0.1% TFA and H2O/0.1% TFA 5:95 to 95:5; flow rate 1.5 mL/
min, detection at 215 nm (YMC-Pack Pro C18, 50 ꢁ 4.6 mm column).
Microwave reactions were carried out using a Biotage Initiator SW version
1.1 build 2795.
General Procedure for the Synthesis of 3-Substituted-7-aryl-
pyrrolo-1,2,4-triazoles
To a solution of 1-phenyl-1-cyclopropanecarboxylic acid (24.0 g, 148 mmol)
in DCM (200 mL) containing DMF (0.5 mL), oxalyl chloride (24.4 g,
193 mmol) was added dropwise. After 1 h, the reaction was concentrated in
vacuo, and the resultant residue was redissolved in DCM (500 mL) and
saturated with NH3(g). After 1.5 h, the reaction was quenched with water
and extracted with DCM. The organic layer was dried over Na2SO4,
filtered, and concentrated in vacuo to provide 1-phenylcyclopropanecarboxa-
mide as an off-white solid. Crude 1-phenylcyclopropanecarboxamide (12.0 g,
74.4 mmol) was suspended in THF (200 mL). Lawesson’s reagent (18.0 g,
44.7 mmol) was added, and the reaction was heated to 708C for 1 h. The
mixture was cooled to room temperature and concentrated in vacuo. The
resultant residue was subjected to silica-gel chromatography eluted with
20–75% EtOAc in hexanes to provide 1-phenylcyclopropanecarbothioamide
1 as an off-white solid. Yield: 10.5 g, 80%, mp 108–1098C. 1H NMR
(400 MHz, CDCl3): d 7.47 (br s, 1H), 7.38–7.46 (m, 4H), 7.32–7.35
(m, 1H), 6.56 (br s, 1H), 2.07 (q, J ¼ 7.1 Hz, 2H), 1.36 (q, J ¼ 7.1 Hz, 2H).
13C NMR (400 MHz, CDCl3): d 139.54, 131.23, 129.56, 128.64, 38.00,
22.42. HRMS calcd. for C10H12NS (M þ 1): 178.0685. Found: 178.0681.
.
Anal. calcd for C10H11NS 0.10 H2O: C, 67.07; H, 6.30; N, 7.82. Found: C,
66.99; H, 6.17; N, 7.62.
Under nitrogen, 1 (4.1 g, 22.9 mmol) was dissolved in dry acetone
(150 mL). Iodomethane (4.9 g, 34.4 mmol) was added, and the solution was
then heated at 458C. After 1.5 h, a precipitate crashed out of the reaction
solution. The reaction continued to be heated for another 1.5 h until com-
pletion as determined by LC/MS. The reaction solution was concentrated in
vacuo to provide 5-(methylthio)-4-phenyl-3,4-dihydro-2H-pyrrolium iodide
2 as a yellow solid. Yield: 7.3 g, .97%. 1H NMR (500 MHz, CDCl3):
d 7.41–7.46 (m, 3H), 7.25 (m, 2H), 4.51 (t, J ¼ 9.2 Hz, 1H), 4.44 (m, 1H),

Synthesis of Fused [5,5]-1,2,4-Triazoles
3383
4.27 (m, 1H), 3.06 (s, 3H), 2.90 (m, 1H), 2.47 (m, 1H). 13C NMR (400 MHz,
CDCl3): d 195.74, 136.62, 129.28, 128.74, 128.67, 56.72, 53.25, 31.67, 14.73.
HRMS calcd. for C11H13NS (M þ 1): 192.0841. Found: 192.0860.
To a solution of 2 (0.100 g, 0.313 mmol) in iPrOH (3 mL), benzhydrazide
(0.064 g, 0.47 mmol) and triethylamine (0.090 mL, 0.65 mmol) were added.
The reaction was heated in a sealed 20-mL scintillation vial at 1508C for
7 h, then cooled to room temperature, and concentrated in vacuo. The
resultant residue was subjected to silica-gel chromatography eluted with
0–3% MeOH in DCM to provide 3,7-diphenyl-6,7-dihydro-5H-pyrrolo
[2,1-c][1,2,4]triazole 3a.
Spectral Data and Elemental Analyses
1
3a: Off-white solid. Yield: .97%, mp 123–1258C. H NMR (400 MHz,
CDCl3): d 7.89 (d, J ¼ 7.1 Hz, 2H), 7.46–7.52 (m, 3H), 7.35–7.36 (m, 4H),
7.26–7.31 (m, 1H), 4.57 (d, J ¼ 7.8 Hz, 1H), 4.23–4.37 (m, 2H), 3.16–
3.35 (m, 1H), 2.72–2.88 (m, 1H). 13C NMR (400 MHz, CDCl3): d 137.54,
131,68, 129.65, 129.32, 128.16, 127.44, 127.36, 127.22, 45.31, 40.04,
38.66. HRMS calcd. for C17H16N3 (M þ 1): 262.1339. Found: 262.1332.
.
.
Anal. calcd. for C17H15N3 2.0H2O 0.4CH2Cl2: C, 63.08; H, 6.02; N,
12.68. Found: C, 63.17; H, 5.72; N, 13.08.
3b: Beige solid. Yield: .97%, mp 115–1168C. 1H NMR (400 MHz, CDCl3):
d 7.33–7.38 (m, 2H), 7.30–7.33 (m, 1H), 7.27–7.29 (m, 2H), 4.62
(t, J ¼ 8.2 Hz, 1H), 4.10–4.19 (m, 2H), 3.28–3.35 (m, 1H), 2.83–2.90
(m, 1H), 2.68 (s, 3H). 13C NMR (400 MHz, CDCl3): d 137.12, 129.33,
128.22, 127.33, 43.09, 40.44, 38.16, 9.86. HRMS calcd. for C12H14N3
(M þ 1): 200.1182. Found: 200.1177.
3c: Yellow oil. Yield: .97%. 1H NMR (400 MHz, CDCl3): d 8.62
(d, J ¼ 4.6 Hz, 1H), 8.34 (d, J ¼ 3.9 Hz, 1H), 7.80–7.84 (m, 1H), 7.33–
7.36 (m, 4H), 7.28–7.32 (m, 2H), 4.54–4.64 (m, 2H), 4.44–4.48 (m, 1H),
3.25–3.32 (m, 1H), 2.76–2.84 (m, 1H). 13C NMR (400 MHz, CDCl3): d
165.02, 150.21, 149.44, 147.67, 139.78, 137.15, 129.16, 127.67, 127.60,
124.10, 121.93, 46.42, 45.62, 39.93, 39.41. HRMS calcd. for C16H15N4
(M þ 1): 263.1291. Found: 263.1284.
1
3d: Beige solid. Yield: 87%, mp 163–1658C. H NMR (400 MHz, CDCl3):
d 9.06 (d, J ¼ 1.5 Hz, 1H), 8.71 (dd, J ¼ 1.7, 4.9 Hz, 1H), 8.32–8.34
(m, 1H), 7.44–7.47 (m, 1H), 7.36–7.39 (m, 4H), 7.28–7.32 (m, 1H), 4.60
(t, J ¼ 7.9 Hz, 1H), 4.36–4.40 (m, 1H), 4.28–4.33 (m, 1H), 3.31–3.38
(m, 1H), 2.85–2.92 (m, 1H). 13C NMR (400 MHz, CDCl3): d 151.01,
146.92, 139.02, 134.30, 129.22, 127.80, 127.59, 124.23, 124.01, 44.31,
39.67, 39.22. HRMS calcd. for C16H15N4 (M þ 1): 263.1291. Found:

3384
C. N. Di Marco and S. D. Kuduk
.
263.1285. Anal. calcd. for C16H14N4 0.15CH2Cl2: C, 70.52; H, 5.24; N,
20.37. Found: C, 70.36; H, 5.34; N, 20.11.
3e: Yellow oil. Yield: 52%. 1H NMR (400 MHz, CDCl3): d 7.37–7.39
(m, 2H), 7.29–7.36 (m, 3H), 4.58 (t, J ¼ 8.0 Hz, 1H), 4.22–4.31 (m, 1H),
4.15–4.22 (m, 1H), 3.29–3.37 (m, 1H), 2.83–2.92 (m, 1H). 13C NMR
(400 MHz, CDCl3): d 129.16, 127.93, 127.24, 43.77, 39.64, 38.65. HRMS
calcd. for C12H11F3N3 (M þ 1): 254.0900. Found: 254.0891.
3f: White solid. Yield: .97%, mp 156–1588C. 1H NMR (400 MHz, CDCl3):
d 7.82 (d, J ¼ 8.9 Hz, 1H), 7.74 (d, J ¼ 6.9 Hz, 1H), 7.32–7.35 (m, 4H),
7.27–7.30 (m, 1H), 7.00 (d, J ¼ 8.9 Hz, 1H), 6.92 (d, J ¼ 7.0 Hz, 1H), 4.57
(t, J ¼ 7.9 Hz, 1H), 4.23–4.34 (m, 2H), 3.27–3.35 (m, 1H), 2.77–2.86
(m, 1H). 13C NMR (400 MHz, CDCl3): d 162.48, 137.50, 129.22, 129.15,
128.03, 127.48, 115.11, 55.64, 45.34, 39.96, 38.50. HRMS calcd. for
C18H18N3O (M þ 1): 292.1445. Found: 292.1442.
1
3g: Beige solid. Yield: 69%, mp 74–768C. H NMR (400 MHz, CDCl3):
d 9.00, (s, 1H), 7.31–7.39 (m, 4H), 7.24–7.26 (m, 1H), 4.65 (t, J ¼ 8.0 Hz,
1H), 4.39–4.43 (m, 1H), 4.27–4.34 (m, 1H), 3.29–3.37 (m, 1H), 2.83–2.92
(m, 1H). 13C NMR (400 MHz, CDCl3): d 138.83, 137.45, 129.44, 128.29,
127.36, 44.13, 39.84, 38.34. HRMS calcd. for C11H12N3 (M þ 1): 186.1026.
Found: 186.1019.
1
3h: Beige solid. Yield: 92%, mp 208–2108C. H NMR (400 MHz, CDCl3):
d 8.37 (d, J ¼ 9.0 Hz, 2H), 8.10 (d, J ¼ 9.0 Hz, 2H), 7.34–7.38 (m, 4H),
7.29–7.32 (m, 1H), 4.61 (d, J ¼ 8.0 Hz, 1H), 4.41–4.45 (m, 1H), 4.30–4.39
(m, 1H), 3.34–3.40 (m, 1H), 2.87–2.95 (m, 1H). 13C NMR (400 MHz,
CDCl3): d 165.42, 148.46, 148.29, 138.59, 133.12, 129.06, 127.68, 127.35,
126.89, 124.42, 44.39, 39.47, 38.98. HRMS calcd. for C17H15N4O2 (M þ 1):
.
307.1190. Found: 307.1173. Anal. calcd. for C17H14N4O2 0.4H2O: C, 65.12;
H, 4.76; N, 17.87. Found: C, 65.11; H, 4.53; N, 18.01.
1
3i: Yellow oil. Yield: .97%. H NMR (400 MHz, CDCl3): d 7.25 ¼ 7.36
(m, 5H), 4.48 (t, J ¼ 7.9 Hz, 1H), 4.16–4.20 (m, 1H), 4.07–4.14 (m, 1H),
3.21–3.25 (m, 1H), 2.71–2.78 (m, 1H), 1.21 (s, 9H). 13C NMR (400 MHz,
CDCl3): d 129.18, 127.75, 127.69, 46.46, 39.62, 39.09, 28.76, 27.33, 8.82.
HRMS calcd. for C15H20N3 (M þ 1): 242.1652. Found: 242.1648.
12a: Off-white solid. Yield: 75%, mp 53–558C. 1H NMR (400 MHz, CDCl3):
d 7.56 (d, J ¼ 7.9 Hz, 2H), 7.28–7.40 (m, 6H), 7.04 (d, J ¼ 7.4 Hz, 2H),
5.77–7.79 (m, 1H), 3.40–3.46 (m, 1H), 3.33–3.38 (m, 2H), 2.09–2.81
(m, 1H). 13C NMR (400 MHz, CDCl3): d 137.40, 131.69, 129.86, 129.46,
129.22, 127.63, 125.43, 123.42, 62.52, 39.45, 20.62. HRMS calcd. for
C17H16N3 (M þ 1): 262.1339. Found: 262.1342.

Synthesis of Fused [5,5]-1,2,4-Triazoles
3385
12b: White solid. Yield: 58%, mp 193–1968C. 1H NMR (400 MHz, CDCl3):
d 7.87–7.89 (m, 2H), 7.54–7.57 (m, 3H), 7.23 (d, J ¼ 8.6 Hz, 2H), 6.89
(d, J ¼ 8.8 Hz, 2H), 4.66 (t, J ¼ 8.1 Hz, 1H), 4.41–4.49 (m, 2H), 3.81
(s, 3H), 3.30–3.37 (m, 1H), 2.85–2.92 (m, 1H). 13C NMR (400 MHz,
CDCl3): d 164.22, 159.33, 131.25, 129.80, 128.58, 127.04, 124.96, 114.61,
55.47, 45.03, 39.26, 38.88. HRMS calcd. for C18H18N3O (M þ 1):
292.1445. Found: 292.1459.
1
12c: Yellow oil. Yield: 70%. H NMR (400 MHz, CDCl3): d 7.78–7.80
(m, 2H), 7.57–7.59 (m, 3H), 5.57 (dd, J ¼ 3.7, 9.3 Hz, 1H), 4.87–4.94
(m, 1H), 3.17 (t, J ¼ 8.0 Hz, 2H), 2.93–2.97 (m, 1H), 1.09
(d, J ¼ 6.4 Hz, 2H), 1.03 (d, J ¼ 6.4 Hz, 2H). 13C NMR (400 MHz,
CDCl3): d 167.30, 131.39, 129.38, 126.93, 124.66, 71.28, 58.60, 34.09,
21.42, 21.12, 20.60. HRMS calcd. for C15H18N3O2 (M þ 1): 272.1394.
Found: 272.1396.
12d: White solid. Yield: 39%, mp 210–2138C. 1H NMR (400 MHz,
CDCl3): d 7.78–7.83 (m, 2H), 7.41–7.49 (m, 3H), 7.28–7.39 (m, 5H),
5.10 (s, 2H), 4.37–4.40 (m, 1H), 4.18–4.22 (m, 1H), 3.37–3.40 (m, 1H),
3.20–3.37 (m, 1H), 2.78–2.79 (m, 1H). 13C NMR (400 MHz, CDCl3): d
131.11, 129.46, 128.75, 128.41, 128.19, 126.87, 125.37, 67.34, 45.85,
44.80, 37.21. HRMS calcd. for C19H19N4O2 (M þ 1): 335.1503. Found:
335.1497.
2,7-Diphenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazole (7)
To a solution of 2 (0.050 g, 0.16 mmol) in iPrOH (3 mL), benzhydrazide
(0.032 g, 0.23 mmol) was added. The reaction was heated via microwave at
2008C for 1 h, then cooled to room temperature, and concentrated in vacuo.
The resultant residue was subjected to silica-gel chromatography eluted
with 0–30% EtOAc in hexanes to provide 7 as a yellow oil. Spectral data
1
and elemental analyses are given as follows: Yield: 0.010 g, 25%. H NMR
(400 MHz, CDCl3): d 8.09–8.12 (m, 2H), 7.33–7.44 (m, 6H), 7.28–7.30
(m, 2H), 4.48 (t, J ¼ 7.6 Hz, 1H), 4.33–4.39 (m, 1H), 4.20–4.27 (m, 1H),
3.22–3.31 (m, 1H), 2.66–2.74 (m, 1H). 13C NMR (400 MHz, CDCl3): d
130.38, 130.10, 129.60, 129.33, 129.19, 128.98, 128.00, 127.45, 126.92,
126.68, 45.92, 40.57, 36.28. HRMS calcd. for C17H16N3 (M þ 1): 262.1339.
Found: 262.1338.
ACKNOWLEDGMENT
The authors thank S. N. Pitzenberger and S. Vargas for NMR determinations
and M. G. Bock for helpful discussions and support.

3386
C. N. Di Marco and S. D. Kuduk
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