An improved synthesis of 1,2,4-triazoles using Ag2CO3

Article abstract of DOI:10.1016/S0040-4020(00)00726-2

An improved synthesis of 1,3,5-trisubstituted 1,2,4-triazoles via Ag₂CO₃ mediated cyclization of triazenes has been developed. This approach is flexible and compatible with a wide range of functional groups. The reaction was complete within 3 h and the products were isolated in moderate to high yields. The influence of the β-substituents of the amines on the triazole formation was also studied. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00726-2

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 8071±8076
An Improved Synthesis of 1,2,4-Triazoles using Ag2CO3
*
K. Paulvannan, Tao Chen and Ron Hale
Affymax Research Institute, 3410 Central Expressway, Santa Clara, CA 95051, USA
Received 3 July 2000; accepted 15 August 2000
AbstractÐAn improved synthesis of 1,3,5-trisubstituted 1,2,4-triazoles via Ag2CO3 mediated cyclization of triazenes has been developed.
This approach is ¯exible and compatible with a wide range of functional groups. The reaction was complete within 3 h and the products were
isolated in moderate to high yields. The in¯uence of the b-substituents of the amines on the triazole formation was also studied. q 2000
Elsevier Science Ltd. All rights reserved.
Introduction
condition make the Buzykin's approach synthetically very
attractive. Despite the mild reaction conditions, to the best
of our knowledge, the synthetic scope and the functional
group tolerance of this reaction have not been fully
exploited. As part of our efforts directed toward the iden-
ti®cation of novel biologically active compounds from
combinatorial libraries of small molecules, we became
interested in investigating the synthetic scope of the
Buzykin's triazole synthesis. In this paper we report our
®ndings on this study and also disclose an ef®cient
Ag2CO3 mediated 1,2,4-triazole synthesis.
Compounds with 1,2,4-triazole moiety have received
considerable attention among medicinal chemists because
molecules with these structural features have been found to
display a wide range of potent biological activities, such as
antihypertensive,1 antifungal2 and antibacterial3 activities.
Appropriately functionalized 1,2,4-triazoles, such as
4-[3,5-bis (2-hydroxyphenyl)-1,2,4-triazol-1-yl]-benzoic
acid, have been shown to selectively form a complex with
iron(III), which is useful in iron overload therapy.4 Consid-
ering the important biological properties of 1,2,4-triazole
compounds, several ef®cient triazole syntheses have been
reported.5
Results and Discussion
Most of the previously reported triazole syntheses made use
of the hydrazonyl chloride 1, readily prepared in a single
step from the corresponding hydrazone, as a common
synthetic intermediate. Conde and co-workers prepared tri-
azole by heating a mixture of the hydrazonyl chloride 1 and
aromatic or aliphatic nitrile in o-dichlorobenzene at 120±
1308C in the presence of one equiv of AlCl3 (Scheme 1).5a
The triazole 2 is formed via a 1,3-dipolar cycloaddition of
nitrilimine, generated in situ from 1 and AlCl3, to nitrile.
Our study began with the preparation of the hydrazonyl
chloride 7a (Scheme 2). Condensation of benzaldehyde
(4) and phenylhydrazine (5a) in benzene gave the hydrazone
Instead of AlCl3, triethylamine (TEA)6 and Ag2CO3 have
7
also been used to generate the nitrilimine intermediate. In an
alternative two-step approach, Buzykin et al. ®rst prepared a
triazene intermediate 3 from the reaction of 1 with a primary
amine and TEA, which was then treated with a solution of
30% hydrogen peroxide/ aqueous KOH to yield the triazole
2 in moderate yield (Scheme 1).5e,5f In this route, the triazole
is believed to form via an azoimine formation, tautomeriza-
tion, cyclization and oxidation.5f Commercial availability of
a large selection of primary amines and the mild reaction
Keywords: hydrazone; nitrilimines; cycloaddition; triazoles.
* Corresponding author. Tel.: 1408 522-5759; fax: 1408-481-9558;
e-mail: kumar_paulvannan@affymax.com
Scheme 1. Preparation of triazole.
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00726-2

8072
K. Paulvannan et al. / Tetrahedron 56 (2000) 8071±8076
Scheme 2. (a) Benzene, rt, 12 h; (b) 1.5 equiv. of NCS, 3 equiv. of DMS, CH2Cl2 08C to 2788C to rt; (c) 1.1 equiv. of 8, 1.1 or 2.2 equiv. of TEA, CH3CN, rt;
12 h; (d) 30% H2O2/sat KOH (90:10 v/v), CH3CN, 08C to rt; (e) 1.2 equiv. of Ag2CO3, CH3CN, 2 h.
6a. After removal of the solvent, the hydrazone 6a was
taken in CH2Cl2 and allowed to react with a N-chlorosuc-
cinimide (NCS)/dimethyl sul®de (DMS) complex under
Patel's reaction conditions8 with slight modi®cation to
furnish the hydrazonyl chloride 7a in 69% yield (for two
steps) after chromatographic puri®cation. The hydrazonyl
chloride 7a was then subjected to triazole formation follow-
ing Buzykin's procedure.5f Accordingly, reaction of 7a with
Table 1. Preparation of triazoles
Entry
Compound
R1
R2
Yield %a
1
2
10a
10b
H
H
Ph±
Ph±CH2±
8a
8b
69 (16)b
62 (8)b
3
4
5
6
10c
10d
10e
10f
H
8c
8d
8e
8f
5 (6)b
H
H
H
40
CH2vCH±
51
47
7
10g
H
8g
37
8
9
10
11
12
10h
10i
10j
10k
101
H
MeO2C±CH2±CH2±
Ph±
Ph±CH2±
Ph±
Ph±CH2±
8h
8a
8b
8a
8b
73
66
48
78
60
OMe
OMe
NO2
NO2
a Overall yield for two steps 7.
b H2O2/KOH method.

K. Paulvannan et al. / Tetrahedron 56 (2000) 8071±8076
8073
Scheme 3. Formation of 1,3-disubstituted triazoles.
1.1 equiv. of benzylamine (8a) and 1.1 equiv. of triethyl-
amine (TEA) in acetonitrile for 24 h provided the triazene
9a. Without puri®cation, the crude triazene 9a in aceto-
nitrile was treated with a solution of aqueous KOH
(5±10% v/v)/30% H2O2 to yield the corresponding triazole
10a in 16% overall yield from 7a, after column chroma-
tography (Table 1, entry 1). It should be noted that after
the addition of KOH/H2O2 mixture the reaction becomes
vigorous and additional precaution should be taken to
avoid any over¯ow or spill by performing the reaction
in a bigger reaction ¯ask at lower temperature (,08C). To
our disappointment, under similar reaction conditions,
2-phenylethylamine (8b) and 2,2-diphenylethylamine (8c)
yielded the corresponding triazoles 10b and 10c in 8 and 6%
yields, respectively (Scheme 2, Table 1, entries 2 and 3).
Isolation of 10b and 10c in low yields was mainly due to the
formation of unidenti®ed side products. One of the identi-
®ed side products was 1,3-disubstituted 1,2,4-triazole 11
(Scheme 3). In the case of amine 8c, in addition to 10c
and 11, benzophenone (12) was also isolated. Furthermore,
when the triazene 9c and KOH/H2O2 were allowed to react
for a longer time (.24 h) the side product 11 was isolated as
the major product and no desired triazole 10c was observed.
When benzylamine (8a) was used no side product 11 was
detected. The isolation of the side products 11 and 12 could
be explained via a two-step, one-pot reaction sequence
(Scheme 3). The ®rst step involves the introduction of a
hydroxyl group at the a-methylene/methine carbon to give
an alcohol intermediate 13 which immediately undergoes a
base promoted fragmentation to yield the undesired side
products 11 and 12. However, no further mechanistic
study was carried out to con®rm this proposed mechanism.
Investigation of the reaction with a range of primary amines
indicated that the nature of the substituent on the b-position
of the amine 8 had a signi®cant impact on the yield of 11
(Scheme 3, R1ˆR2ˆPh 60% yield; R1ˆPh, R2ˆH 6%
yield). Isolation of 11 in moderate yield (60%) from 7a
and 8c suggests that this approach can be used as an alter-
native to the existing routes to prepare 1,3-disubstituted
1,2,4-triazoles. In addition to side products formation,
building blocks with carbon±carbon double bond, thioether,
tertiary amine and ester functionalities could not be used
under the KOH/H2O2 conditions because they were suscept-
ible to either oxidation or hydrolysis. Limited functional
group compatibility and isolation of triazoles in low yields
made Buzykin's approach unsuitable for combinatorial
library preparation. These limitations led us to examine an
alternative reaction condition that would tolerate a wide
range of funtionalities and provide triazoles in synthetically
useful yield.
Based on the above results, we reasoned that replacing the
KOH/H2O2 mixture with a milder reagent would make this
approach compatible with more functionalities and suppress
the side product formation. We began our investigation by
treating the triazene 9a with various organic and inorganic
reagents, such as TEA, DIEA, KF, NaHCO3, Cs2CO3,
K2CO3 and Ag2CO3. Accordingly, the triazene 9a in
CH3CN was treated with 1.5 equiv. of the reagent and the
reaction progress was monitored by thin layer chroma-
tography (TLC) and LC/MS. Among all the reagents
examined, Ag2CO3 smoothly promoted the cyclization and
provided the triazole 10a in 69% yield over the two steps
from 7a (Scheme 2, Table 1, entry 1). The reaction was very
clean and complete within 3 h. In the absence of Ag2CO3,
only a trace of the triazole 10a was observed, indicating that
Ag2CO3 was necessary to convert the triazene 9a into tri-
azole 10a. Presumably, the oxidizing property of Ag2CO3
may have contributed in the cyclization of the triazene 9a to
the triazole 10a via an azoimine formation, tautomerization,
cyclization and oxidation, as proposed by Buzykin.5f To the
best of our knowledge, this is the ®rst example of silver
carbonate promoted synthesis of triazole from triazene. In
addition to promoting the triazole formation under mild
reaction condition, use of solid Ag2CO3 simpli®es the
work-up procedure by eliminating the aqueous work-up.
Removal of CH3CN followed by puri®cation of the crude
mixture provided the triazole 10a.
In order to examine the synthetic scope and the functional
group tolerance of the Ag2CO3 mediated synthesis, the reac-
tion sequence was studied with a variety of primary amines
8b±h and hydrazines 5b,c (Table 1, entries 2±12). Treat-
ment of amines 8b±h with hydrazonyl chloride 7a provided
the corresponding triazenes 9b±h, which were then treated
with Ag2CO3 to give the desired triazoles 10b±h (Table 1
entries 2±8). As shown in Table 1, in most of the cases, the
desired triazoles were isolated in synthetically useful yields.
The amines 8b and 8c provided the corresponding triazoles
10b and 10c in 62% and 5% yields, respectively. To our
disappointment, use of Ag2CO3 failed to improve the yield
of 10c and the side product 11 was isolated as the major
product (.60%). No further optimization study was carried
out to suppress the side product 11 formation. In the case of
amines 8f and 8g, the corresponding triazoles 10f and 10g
were isolated in moderate yields without any N-oxide
formation, whereas Buzykin's KOH/H2O2 route yielded
the corresponding N-oxides along with 10f and 10g. The
ester and vinyl functionalities present in the triazoles 10e
and 10h, respectively, could be used as handles to introduce
additional structural diversity.

8074
K. Paulvannan et al. / Tetrahedron 56 (2000) 8071±8076
Given the success in isolating the triazoles in moderate
yields, we then examined the in¯uence of electronically
different hydrazines on the triazole formation. The hydra-
zonyl chlorides 7b9 and 7c, prepared from 4-methoxy and 4-
nitrophenylhydrazine (5b) and (5c), respectively, were
subjected to the triazole synthesis with amines 8a and 8b.
Under the above reaction conditions, the cyclization
proceeded smoothly and yielded the corresponding triazoles
10i±l in moderate yields (Scheme 2, Table 1, entries 9±12),
indicating that the electronic effect did not have any major
impact on the triazole formation.
General procedure for the preparation of triazoles 10a±l
Ag2CO3 method. To a solution of hydrazonyl chloride 7
(1.64 mmol, 1.0 equiv.) in CH3CN (8 mL) were added
amine 8 (1.1 equiv.) and TEA (1.1 equiv.; 2.2 equiv. for
amine 8h) and the reaction mixture was stirred at rt for
12 h to yield the triazene 9 (1.64 mmol). After removal of
the solvent, the crude 9 was taken in fresh CH3CN (8 mL)
and Ag2CO3 (0.68 g, 2.46 mmol, 1.5 equiv.) was added and
the reaction mixture was stirred at room temperature for
2±3 h. The solvent was evaporated and the residue was
puri®ed by ¯ash column chromatography (hexane/EtOAc)
to provide triazole 10.
Conclusion
KOH/H2O2 method. To a solution of crude triazene 9
(1.64 mmol) in CH3CN (7 mL) at 08C was added 7 mL of
a (90:10 v/v) mixture of 30% H2O2 and sat. KOH (5 g in
10 mL of H2O) and the reaction mixture was stirred at rt
until disappearance of the triazene 9. The reaction mixture
was then diluted with EtOAc and washed with water. The
solvent was evaporated and the residue was puri®ed by ¯ash
column chromatography (hexane/EtOAc) to afford triazole
10.
We have described an improved synthesis of 1,3,5-trisub-
stituted 1,2,4-triazoles via Ag2CO3 mediated cyclization of
triazene. The reaction was fast and, in most cases, the tri-
azoles were isolated in synthetically useful yields. The
impact of the b-substituent of the amine on the yield of
the triazole has been studied. This approach is compatible
with a wide range of functional groups, which is a valuable
advantage over the previously reported method. Commer-
cial availability of a diverse collection of primary amines
and aldehydes makes this route suitable for the preparation
of large numbers of triazoles. This approach is also
amenable to scale-up. We are currently optimizing the tri-
azole synthesis on solid support and the results will be
published in due course.
Compound 10a. IR (neat): nmax 3383, 1493, 1474, 1440,
1394, 1341 cm21; 1H NMR (CDCl3) d: 7.34±7.50 (m, 11H),
7.54±7.58 (m, 2H), 8.22±8.26 (m, 2H); 13C NMR (CDCl3)
d: 125.5, 126.7, 128.1, 128.7, 128.9, 129.1, 129.5, 130.1,
130.9, 138.4, 154.9, 162.1; HRMS (FAB) calcd for
C20H16N3 (M1H) 298.1344, found 298.1350.
Experimental
General methods
All solvents and reagents were purchased from commercial
sources and used without further puri®cation. H NMR
1
spectral data were obtained on a Varian Gemini 400 instru-
ment with the solvents noted. Chemical shifts were reported
in the d scale in ppm relative to TMS (0.00 ppm) as internal
standard. 13C NMR spectra were obtained by using the
above instrument operating at 100 MHz with solvents noted.
General procedure for the preparation of hydrazonyl
chloride 7a±c
Compound 10b. Mp 83±848C; IR (neat): nmax 3377, 3056,
1
3025, 1595, 1501, 1448, 1348 cm21; H NMR (CDCl3) d:
To a solution of benzaldehyde (4) (1.0 g, 9.43 mmol,
1.0 equiv.) in benzene (40 mL) was added hydrazine 5
(9.43 mmol, 1.0 equiv.) and the reaction mixture was stirred
at rt for 12 h. Removal of the solvent provided the crude
hydrazone 6, which was used in the next step without further
puri®cation. To a solution of NCS (1.89 g, 14.15 mmol,
1.5 equiv.) in CH2Cl2 (25 mL) at 08C was added dimethyl-
sul®de (1.76 g, 28.29 mmol, 3.0 equiv.) and the reaction
mixture was stirred for 15 min at this temperature and
then cooled to 2788C. To this solution was added the hydra-
zone 6 (9.43 mmol, 1.0 equiv.) in CH2Cl2 (25 mL) and the
reaction mixture was stirred for 1 h at this temperature and
then allowed to warm to rt and stirred at rt for 2 h. The
solvent was evaporated and the residue was puri®ed by
¯ash column chromatography (hexane/EtOAc 98:2 to
90:10) to afford the hydrazonyl chloride 7.
4.23 (s, 2H), 7.16±7.18 (m, 2H), 7.22±7.29 (m, 3H), 7.36±
7.38 (m, 2H), 7.41±7.48 (m, 6H), 8.17±8.20 (m, 2H); 13C
NMR (CDCl3) d: 32.7, 125.5, 126.7, 127.1, 128.6, 128.7,
128.8, 129.2, 129.4, 129.5, 131.0, 136.1, 137.5, 155.1,
161.8; HRMS (FAB) calcd for C21H18N3 (M1H)
312.1501, found 312.1503.

K. Paulvannan et al. / Tetrahedron 56 (2000) 8071±8076
8075
Compound 10c. IR (neat): nmax 3417, 1640, 1494,
Compound 10g. IR (neat): nmax 3409, 1680, 1494, 1441,
1196, 1123 cm21 1H NMR (DMSO-d6) d: 2.61 (t,
1
1441 cm21; H NMR (DMSO-d6) d: 5.47 (s, 1 H), 7.21±
;
7.49 (m, 18H), 8.17 (m, 2H); 13C NMR (DMSO-d6) d: 48.4,
126.0, 126.7, 127.2, 128.5, 128.7, 128.9, 129.3, 129.4,
129.5, 131.1, 137.4, 140.5, 157.1, 161.8; HRMS (FAB)
calcd for C27H22N3 (M1H) 388.1814, found 388.1910.
Jˆ4.8 Hz, 4H), 3.67 (s, 2H), 3.69 (t, Jˆ4.8 Hz, 4H),
7.38±7.53 (m, 6H), 7.72±7.76 (m, 2H), 8.13±8.17 (m,
2H); 13C NMR (DMSO-d6) d: 53.0, 53.2, 66.8, 124.8,
126.5, 128.6, 128.9, 129.3, 129.4, 130.6, 137.6, 152.0,
161.4; HRMS (FAB) calcd for C19H21N4O (M1H)
321.1715, found 321.1713.
Compound 10d. IR (neat): nmax 3317, 3065, 2966, 2926,
1
1593, 1501, 1441, 1355, 1109 cm21; H NMR (CDCl3) d:
1.37 (d, Jˆ6.8 Hz, 6H), 3.16 (m, 1H), 7.36±7.57 (m, 8H),
8.14±8.17 (m, 2H); 13C NMR (CDCl3) d: 21.8, 26.0, 125.7,
126.6, 128.6, 129.1, 129.2, 129.5, 131.2, 137.7, 161.5,
162.0; HRMS (FAB) calcd for C17H18N3 (M1H)
264.1501, found 264.1495.
Compound 10h. Mp 78±798C; IR (neat): nmax 3436, 1733,
1646, 1494, 1434, 1355 cm21; 1H NMR (CDCl3) d: 2.95 (t,
Jˆ7.3 Hz, 2H), 3.12 (t, Jˆ7.3 Hz, 2H), 3.68 (s, 3H), 7.36±
7.54 (m, 8H), 8.12 (m, 2H). 13C NMR (CDCl3) d: 21.9, 31.4,
51.8, 125.0, 126.4, 128.5, 128.9, 129.2, 129.5, 130.9, 137.3,
155.2, 161.3, 172.5; HRMS (FAB) calcd for C18H18N3O2
(M1H) 308.1399, found 308.1400.
Compound 10e. Mp 75±778C; IR (neat): nmax 3516, 1640,
1
1487, 1441, 1341 cm21; H NMR (CDCl3) d: 5.68 (dd,
Jˆ10.8, 1.8 Hz, 1H), 6.53 (dd, Jˆ17.4, 1.8 Hz, 1H), 6.64
(dd, Jˆ17.4, 10.8 Hz, 1H), 7.41±7.56 (m, 8H), 8.18±8.22
(m, 2H); 13C NMR (CDCl3) d: 121.7, 123.8, 125.4, 126.6,
128.6, 129.1, 129.4, 129.5, 130.8, 137.1, 152.9, 161.8;
HRMS (FAB) calcd for C16H13N3 (M1H) 248.1188,
found 248.1197.
Compound 10i. Mp 95±978C; IR (neat): nmax 3410, 3059,
1
2833, 1640, 1507, 1474, 1440, 1288, 1242 cm21; H NMR
(DMSO-d6) d: 3.85 (s, 3H), 6.93 (d, Jˆ8.8 Hz, 2H), 7.31±
7.46 (m, 8H), 7.55 (m, 2H), 8.21 (m, 2H); 13C NMR
(DMSO-d6) d: 55.7, 114.7, 126.7, 127.0, 128.2, 128.7,
129.0, 129.5, 130.0, 131.0, 131.5, 154.8, 159.9, 161.8;
HRMS (FAB) calcd for C21H18N3O (M1H) 328.1450,
found 328.1452.
Compound 10f. Mp 124±1268C; IR (neat): nmax 3397,
1
1646, 1487, 1441, 1408, 1348 cm21; H NMR (CDCl3) d:
7.31 (ddd, Jˆ8.0, 4.8, 0.8 Hz, 1H), 7.39±7.49 (m, 8H), 7.89
(dt, Jˆ7.8, 2.0 Hz, 1H), 8.19±8.23 (m, 2H), 8.63 (dd,
Jˆ4.8, 2.0 Hz, 1H), 8.77 (d, Jˆ2.0 Hz, 1H); 13C NMR
(CDCl3) d: 123.2, 124.3, 125.4, 126.5, 128.6, 129.3,
129.5, 129.6, 130.3, 136.0, 137.7, 149.3, 150.6, 151.9,
162.2; HRMS (FAB) calcd for C19H15N4 (M1H)
299.1297, found 299.1298.
Compound 10j. IR (neat): nmax 3377, 2833, 1633, 1514,
1
1448, 1348, 1249 cm21; H NMR (DMSO-d6) d: 3.85 (s,
3H), 4.17 (s, 2H), 6.94 (m, 2H), 7.15 (m, 2H), 7.20±7.26 (m,
5H), 7.38±7.46 (m, 3H), 8.15 (m, 2H); 13C NMR (DMSO-
d6) d: 32.6, 55.7, 114.6, 126.6, 127.0, 128.6, 128.7, 128.8,
129.4, 130.4, 131.1, 136.2, 155.3, 160.2, 161.6; HRMS
(FAB) calcd for C22H20N3O (M1H) 342.1606, found
342.1598.

8076
K. Paulvannan et al. / Tetrahedron 56 (2000) 8071±8076
Goldschmidt, R. M.; Loeloff, M. J.; Webb, G. C.; Barrett, J. F.
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R.; Schnebli, H. P. Angew. Chem., Int. Ed. Engl. 1999, 38, 2568.
5. (a) Conde, S.; Corral, C.; Madronero, R. Synthesis 1973, 28.
(b) Broggini, G.; Garanti, L.; Molteni, G.; Zecchi, G. Synthesis
1995, 1483. (c) Neidlein, R.; Sui, Z. Helv. Chim. Acta. 1991, 74,
501. (d) Hoque, A. K. M. M.; Kovelesky, A. C.; Lee, W.; Shine,
H. J. Tetrahedron Lett. 1985, 26, 5655. (e) Buzykin, B. I.;
Bredikhina, Z. A.; Molodykh, A. V. Bull. Acad. Sci. USSR 1991,
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M. K.; Weber, P. C.; Alexander, R. S.; Kettner, C. A.; Pruitt,
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Bioorg. Med. Chem. Lett. 1998, 8, 775. (h) Farag, A. M.; Shawali,
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Compound 10k. Mp 162±1648C; IR (neat): nmax 3390,
1600, 1520, 1487, 1441, 1341, 1275 cm21 1H NMR
;
(DMSO-d6) d: 7.39±7.49 (m, 6H), 7.51±7.54 (m, 2H),
7.58±7.62 (m, 2H), 8.18±8.22 (m, 2H), 8.24±8.28 (m,
2H); 13C NMR (DMSO-d6) d:124.8, 125.2, 126.7, 127.6,
128.7, 129.0, 129.1, 129.9, 130.1, 130.7, 142.9, 146.8,
155.3, 162.6; HRMS (FAB) calcd for C20H15N4O2 (M1H)
343.1195, found 343.1197.
Compound 10l. Mp 152±1548C; IR (neat): nmax 3364,
7. (a) Broggini, G.; Garanti, L.; Molteni, G.; Zecchi, G.
Tetrahedron: Asymmetry 1999, 10, 487. (b) Broggini, G.;
Casalone, G.; Garanti, L.; Molteni, G.; Pilati, T.; Zecchi, G. Tetra-
hedron: Asymmetry 1999, 10, 4447. (c) Broggini, G.; Bruche, L.;
Garanti, L.; Zecchi, G. J. Chem. Soc., Perkin Trans. 1 1994, 433.
(d) Broggini, G.; Garanti, L.; Molteni, G.; Zecchi, G. Heterocycles
2000, 53, 831. (e) Broggini, G.; Garanti, L.; Molteni, G.; Zecchi, G.
Heterocycles 2000, 53, 917.
1
1593, 1527, 1487, 1448, 1348 cm21; H NMR (DMSO-d6)
d: 4.33 (s, 2H), 7.18±7.34 (m, 5H), 7.44±7.51 (m, 3H),
7.60±7.64 (m, 2H), 8.18±8.21(m, 2H), 8.30±8.33 (m,
2H); 13C NMR (DMSO-d6) d: 33.2, 124.8, 124.9, 126.6,
127.4, 128.3, 128.7, 129.0, 129.8, 130.2, 135.2, 142.3,
147.0, 155.1, 162.3; HRMS (FAB) calcd for C21H17N4O2
(M1H) 357.1352, found 357.1345.
8. Patel, H. V.; Vyas, K. A.; Pandey, S. P.; Fernandes, P. S.
Tetrahedron 1996, 52, 661.
Acknowledgements
9. Treatment of hydrazine 6b with NCS/DMS, under our modi®ed
reaction condition, gave a separable mixture of 7b and 14.
The authors thank Dr Dennis Solas, Dr Ted Baer and Dr
Mike C. Needels for helpful suggestions. The authors also
thank Mr Daniel Sedehi, Northwestern University, for his
assistance in this project.
References
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