Catalyst-free synthesis of N-rich heterocycles via multi-component reactions

Article abstract of DOI:10.1016/j.tet.2012.02.051

Efficient and straightforward methods for the synthesis of 5-substituted 1H-tetrazoles via multi-component reaction of α-dicarbonyl compounds, 2,3-diaminomaleonitrile and sodium azide without any catalyst has been reported. These general protocols provide a wide variety of N-rich heterocyclic compounds (1H-tetrazole-5-yl) pyrazines and di(1H-tetrazole-5-yl) pyrazines, in good to excellent yields.

Full text of DOI:10.1016/j.tet.2012.02.051

Tetrahedron 68 (2012) 3351e3356
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Catalyst-free synthesis of N-rich heterocycles via multi-component reactions
,
a
b
a,
*
Zeinab Noroozi Tisseh a, Minoo Dabiri a , Mohsen Nobahar , Ali Abolhasani Soorki , Ayoob Bazgir
*
a Department of Chemistry, Shahid Beheshti University G.C., Tehran 1983963113, Iran
b Research Institute of Applied Sciences, Academic Center for Education, Culture and Research, Shahid Beheshti University, Tehran, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Efficient and straightforward methods for the synthesis of 5-substituted 1H-tetrazoles via multi-
component reaction of -dicarbonyl compounds, 2,3-diaminomaleonitrile and sodium azide without
any catalyst has been reported. These general protocols provide a wide variety of N-rich heterocyclic
compounds (1H-tetrazole-5-yl) pyrazines and di(1H-tetrazole-5-yl) pyrazines, in good to excellent
yields.
Received 1 November 2011
Received in revised form 31 January 2012
Accepted 21 February 2012
Available online 25 February 2012
a
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Tetrazole
Pyrazine
Multi-component
Azide
1. Introduction
the presence of hydrazoic acid, which is toxic and explosive. In
addition, all of the known methods use organic solvents, in par-
One of the main challenges in medicinal chemistry is the design
and synthesis of biologically active molecules. Multi-component
reactions (MCRs), because of their productivity, simple pro-
cedures, convergence, facile execution, and atom economy,1 are one
of the best tools in the synthesis of diverse and complex com-
pounds as well as small and drug like heterocycles.2 In this context,
tetrazole derivatives show interesting features that make them
attractive for use in MCRs.
Tetrazoles are a class of heterocycles with a wide range of ap-
plications that are receiving considerable attention. This functional
group has a role in coordination chemistry as ligands,3 in materials
science as specialty explosives and information recording systems,
as good potential inhibitors and as intermediates in a variety of
synthetic transformations. Moreover, the tetrazole groups have
found use in pharmaceuticals as lipophilic spacers and carboxylic
acid surrogates. Also the tetrazole ring appears in some well-
known drugs.4 Therefore, a number of methods have been repor-
ted for the preparation of tetrazoles.5 One of the major synthetic
routes to tetrazole formation is the [2þ3] cycloaddition of an
organonitrile and an azide salt.6
ticular, dipolar aprotic solvents, such as DMF.7,3b Recently, Sharpless
and co-workers reported an improved preparation of tetrazoles by
the reaction of nitriles and NaN3 in the presence of Zn (II) salts in
water. In the case of sterically hindered aromatic or deactivated
alkyl nitriles, high temperature (140e170 ꢀC) and long reaction
times are required.8
Thus, the development of a convenient and safe process for the
preparation of new tetrazole derivatives is an interesting problem
for investigation. Although limited number of isocyanide-based
multi-component reactions have been reported for the synthesis
of tetrazoles,9 to the best of our knowledge, the synthesis of tet-
razole fused heterocycles via diaminomaleonitrile-based multi-
component reactions has not been reported yet.
Therefore, as part of our program aimed for the preparation of
new heterocycles,10 guided by observation that the presence of two
or more different heterocyclic moieties in a molecule often en-
hances the biological profile remarkably, we investigated herein, an
efficient synthesis of terazoles containing pyrazine moiety via
diaminomaleonitrile-based multi-component reactions. We seek to
replace the environmentally harmful solvents, i.e., DMF with di-
methyl sulfoxide (DMSO) as an environmentally friendly solvent.
According to the U.S. Food and Drug Administration (FDA) solvent
classification based on their possible risk to human health, DMSO
belong to class 3, which is defined as solvent with low toxic potential
(solvent with low toxic potential to humans; no health-based ex-
posure limit is needed).11
However, many of these protocols have some disadvantages,
such as the use of toxic metals, strong Lewis acid, expensive re-
agents, low yield, harsh reaction conditions, water sensitivity, and
* Corresponding authors. Fax: þ98 21 22431661; e-mail address: a_bazgir@
sbu.ac.ir (A. Bazgir).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.02.051

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Z.N. Tisseh et al. / Tetrahedron 68 (2012) 3351e3356
2. Results and discussion
aureus ATCC 25923 (Gram-positive bacteria), Candida albicans ATCC
10231, and Saccharomyses cerevisiae ATCC 9763 (fungi). The mini-
mum inhibitory concentration (MIC) of the synthesized compounds
determined by microdillution method12 (Table 4). As can be seen
from Table 4, good to improved antibacterial activity was observed
for mostof the compounds 5 against all species of Gram-positive and
Gram-negative bacteria and fungi used in the study. Compounds 3
don’t have anyactivityagainst all microorganisms used in this study.
The choice of an appropriate reaction medium is of crucial
importance for successful synthesis. Initially, the three-component
reaction of oxalaldehyde 1a, 2,3-diaminomaleonitrile 2, and so-
dium azide as a simple model substrate was investigated in dif-
ferent solvents without any catalyst (Table 1). The desired product
was scarcely obtained in non-polar solvents (entries 8e10) and
even methanol, ethanol, and water as a polar protic solvent failed
to produce the desired product in good yield (entries 5e7). It was
found that DMSO is the best solvent with respect to reaction yield
(entry 2). We performed the model reaction using different
quantities of reagents in DMSO (entries 1e3). The best result
was obtained with a 1:1:1.5 ratio of oxalaldehyde 1a, 2,3-
diaminomaleonitrile 2, and sodium azide.
3. Conclusion
In conclusion, an efficient, catalyst-free and convenient method
for the preparation of tetrazoles containing pyrazine in DMSO is
reported. To the best of our knowledge, it is the first example of
a multi-component reaction to synthesis of these compounds. The
present green synthesis shows attractive characteristics, such as
one-pot conditions, short reaction times, easy work-up/purification
and reduced waste production without using any catalyst or addi-
tive agent.
Table 1
Model reaction, conditions, and yielda
4. Experimental
4.1. General
Melting points were measured on an Electrothermal 9100 ap-
paratus and are uncorrected. 1H and 13C NMR spectra were recor-
ded on a BRUKER DRX-300 AVANCE spectrometer at 300.13 and
75.47 MHz, respectively. 1H and 13C NMR spectra were obtained on
solutions in DMSO-d6. IR spectra were recorded using a BOMEM
MB-Series. Elemental analyses were performed using a Heracus
CHNeO-Rapid analyzer.
Entry
Conditions
NaN3 (mmol)
Yield (%)
1
2
3
4
5
6
7
8
9
10
DMSO (100 ꢀC)
DMSO (100 ꢀC)
DMSO (100 ꢀC)
DMF (100 ꢀC)
H2O (reflux)
MeOH (reflux)
EtOH (reflux)
Benzene (reflux)
Toluene (reflux)
CHCl3 (reflux)
1
1.5
2
1.5
1.5
1.5
1.5
1.5
1.5
1.5
63
91
90
84
43
Trace
Trace
Trace
Trace
Trace
The chemicals used in this work were obtained from Fluka and
Merck and were used without purification.
4.1.1. Typical procedure for the preparation of 3-(1H-tetrazole-5-yl)
pyrazine-2-carbonitrile (3a). A mixture of oxalaldehyde (1 mmol),
2,3-diaminomaleonitrile (1 mmol), and sodium azide (1.5 mmol) in
DMSO (2 mL) was stirred at 100 ꢀC for 3 h. After completion of the
reaction confirmed by TLC (eluent: EtOAc/n-hexane, 1:1), the sol-
vent was removed. To the residue was added 10 mL of 2 N HCl with
vigorous stirring causing the 3-(1H-tetrazole-5-yl) pyrazine-2-
carbonitrile 3a as cream powder (0.16 g, yield 91%). Mp
178e180 ꢀC; [found: C, 41.55; H, 1.68; N, 56.54. C6H3N7 requires C,
41.62; H, 1.75; N, 56.63%]; Rf (EtOAc/n-hexane, 1:1) 0.45; nmax (KBr):
a
Oxalaldehyde (1 mmol), diaminomaleonitrile (1 mmol). Reaction time¼3 h.
To explore the scope and limitations of this reaction, the pro-
cedure was extended to various aliphatic and aromatic
a-dicar-
bonyl compounds 1aee and corresponding (1H-tetrazole-5-yl)
pyrazine-2-carbonitrile 3aee were synthesized in DMSO at 100 ꢀC
(Table 2). The reaction proceeded very cleanly in the absence of any
catalyst. The catalyst-free reactions carried out in DMSO are safe,
non-toxic, environmentally friendly, and inexpensive. The absence
of catalyst for the reaction avoids the use of moisture-sensitive
heavy metals, such as Lewis acids.
Mechanistically, the formation of products can be rationalized
by initial formation of pyrazine-2,3-dicarbonitrile 4 by a conden-
sation reaction of 1 and 2. Subsequent [2þ3] cycloaddition reaction
of 4 with the sodium azide to afford product 3 (Scheme 1). To clarify
the proposed mechanism, first, the pyrazine-2,3-dicarbonitrile 4a
was synthesized from condensation of 1a and 2, subsequently re-
action of 4a with sodium azide afforded corresponding product 3a.
During our investigation on the synthesis of tetrazoles fused
pyrazine, we found that increasing the reaction time and amount of
the sodium azide afforded new tetrazoles, di(1H-tetrazole-5-yl)
pyrazines 5aeg, in good to excellent yields under same reaction
conditions (Table 3).
Encouraged by these results, ninhydrin 6 was selected as
dicarbonyl compound, the reactions proceeded very efficiently and
led to the formation of the corresponding di(1H-tetrazole-5-yl)-9H-
indeno[2,1-b]pyrazin-9-one 7 in 89% yield (Scheme 2).
Finally, selective synthesized compounds were screened for an-
timicrobial activity. The microorganisms used in this study were
Escherichia coli ATCC 25922, Pseudomonas aeruginusa ATCC 85327,
(Gram-negative bacteria), Bacillus subtilis ATCC 465, Staphylococcus
3401, 2128, 1673, 1540 cmꢁ1
; dH (300 MHz, DMSO-d6) 8.73 (1H, s,
CH), 8.94 (1H, s, CH); dC (75 MHz, DMSO-d6) 117.2, 126.4, 143.9,
147.9, 148.1, 158.0; MS, m/z: 173 (Mþ).
4.1.2. 5,6-Dimethyl-3-(1H-tetrazole-5-yl)pyrazine-2-carbonitrile
(3b). Cream powder (0.17 g, yield 83%). Mp 199e201 ꢀC; [found: C,
47.66; H, 3.59; N, 48.81. C8H7N7 requires C, 47.76; H, 3.51; N,
48.73%]; Rf (EtOAc/n-hexane, 1:1) 0.41; nmax (KBr): 3426, 2230,
1600, 1549 cmꢁ1
; dH (300 MHz, DMSO-d6) 2.63 (3H, s, CH3), 2.69
(3H, s, CH3); dC (75 MHz, DMSO-d6) 22.2, 22.7, 116.0, 123.9, 139.4,
153.0, 156.3, 157.8; MS, m/z: 201 (Mþ).
4.1.3. 5,6-Diphenyl-3-(1H-tetrazole-5-yl)pyrazine-2-carbonitrile
(3c). Light yellow powder (0.28 g, yield 88%) mp 163e165 ꢀC;
[found: C, 66.53; H, 3.35; N, 30.20. C18H11N7 requires C, 66.45; H,
3.41; N, 30.14%]; Rf (EtOAc/n-hexane, 1:1) 0.43; nmax (KBr): 3425,
2237, 1524, 1448 cmꢁ1
; dH (300 MHz, DMSO-d6) 7.40e7.62 (10H, m,
HeAr); dC (75 MHz, DMSO-d6) 115.9, 124.4, 128.8, 128.9, 130, 130.4,
130.7, 136.5, 136.6, 139.7, 153.2, 153.5, 154.3; MS, m/z: 325 (Mþ).
4.1.4. 5,6-Bis(4-fluorophenyl)-3-(1H-tetrazole-5-yl)pyrazine-2-
carbonitrile (3d). Cream powder (0.29 g, yield 81%). Mp

Z.N. Tisseh et al. / Tetrahedron 68 (2012) 3351e3356
3353
Table 2
Synthesis of (1H-tetrazole-5-yl) pyrazine-2-carbonitrile 3.
Product
Time (h)
Yield (%)
91
3
3a
3.5
83
88
3b
3
3c
3.5
81
3d
3.5
78
3e
Scheme 1. Proposed mechanism of the reaction.
130e132 ꢀC; [found: C, 59.73; H, 2.45; N, 27.08. C18H9F2N7 requires
C, 66.45; H, 3.41; N, 30.14%]; Rf (EtOAc/n-hexane, 1:1) 0.51; nmax
C, 62.33; H, 3.92; N, 25.44%.]; Rf (EtOAc/n-hexane, 1:1) 0.47; nmax
(KBr): 3469, 2225, 1606, 1549 cmꢁ1
dH (300 MHz, DMSO-d6) 3.79
(3H, s, OCH3), 3.80 (3H, s, OCH3), 6.97e7.63 (8H, m, HeAr); dC
(75 MHz, DMSO-d6) 55.7, 55.8, 114.4, 114.5, 116.1, 123.3, 128.8, 129,
131.5, 131.7, 132, 138.7, 152.7, 153.4, 161, 161.4; MS, m/z: 385 (Mþ).
;
(KBr): 3442, 2237, 1606, 1498 cmꢁ1
;
dH (300 MHz, DMSO-d6) 7.29
(4H, m, HeAr), 7.54 (2H, m, HeAr), 7.66 (2H, m, HeAr); dC (75 MHz,
DMSO-d6) 116.3, 124.3, 132.4, 132.5, 132.8, 132.9, 133, 139.5, 152.6,
152.9, 153.4, 161.8, 162; MS, m/z: 361 (Mþ).
4.1.6. Typical procedure for the preparation of 2,3-di(1H-tetrazole-5-
yl)pyrazine (5a). A mixture of oxalaldehyde (1 mmol) 2,3-
diaminomaleonitrile (1 mmol), sodium azide (3 mmol) in DMSO
(2 mL) was stirred at 100 ꢀC for 6 h. After completion of the reaction
4.1.5. 5,6-Bis(4-methoxyphenyl)-3-(1H-tetrazole-5-yl)pyrazine-2-
carbonitrile (3e). Yellow powder (0.30 g, yield 78%). Mp
124e126 ꢀC; [found: C, 62.45; H, 3.99; N, 25.51. C20H15N7O2 requires

3354
Z.N. Tisseh et al. / Tetrahedron 68 (2012) 3351e3356
Table 3
Synthesis of di(1H-tetrazole-5-yl) pyrazines 5
Product
Time (h)
Yield (%)
6
93
5a
5b
5c
5d
6.5
6.5
81
83
6
85
92
6.5
5e
5f
7.5
7.5
81
88
5g
confirmed by TLC (eluent: EtOAc/n-hexane, 1:1), the solvent was
evaporated under reduced pressure. To the participate was added
20 mL of 2 N HCl with vigorous stirring causing the 2,3-di(1H-
tetrazole-5-yl) pyrazine to precipitate. The precipitate was filtered
and dried in a drying oven to furnish the 2,3-di(1H-tetrazole-5-yl)
5a as white powder (0.20 g, yield 93%). Mp 257e259 ꢀC; [found: C,
33.25; H, 1.82; N, 64.73. C6H4N10 requires C, 33.34; H, 1.87; N,
64.80%.]; Rf (EtOAc/n-hexane, 1:1) 0.56; nmax (KBr): 3469, 2225,
1606, 1549 cmꢁ1
;
dH (300 MHz, DMSO-d6) 3.79 (3H, s, OCH3), 39.09
(2H, s, HeAr); dC (75 MHz, DMSO-d6) 140.2, 146.5, 153.7; MS, m/z:
216 (Mþ).
4.1.7. 2,3-Dimethyl-5,6-di(1H-tetrazole-5-yl) pyrazine (5b). Cream
powder (0.20 g, yield 81%). Mp 230e232 ꢀC; [found: C, 39.22; H,
3.23; N, 57.27. C8H8N10 requires C, 39.34; H, 3.30; N, 57.35%.]; Rf
(EtOAc/n-hexane, 1:1) 0.51; nmax (KBr): 3425, 1631, 1543 cmꢁ1
; dH

Z.N. Tisseh et al. / Tetrahedron 68 (2012) 3351e3356
3355
Scheme 2. Synthesis of di(1H-tetrazole-5-yl)-indenopyrazin 6.
Table 4
MIC ( g/ml) values of products
C, 56.19; H, 3.67; N, 32.60. C20H16N10O2 requires C, 56.07; H,
m
3.76; N, 32.69%.]; Rf (EtOAc/n-hexane, 1:1) 0.48; nmax (KBr): 3538,
1543, 1454 cmꢁ1
; dH (300 MHz, DMSO-d6) 3.78 (6H, s, OMe), 6.99
Microorganisms
Products
(4H, d, J 8.1 Hz, HeAr), 7.47e7.60 (4H, m, HeAr); dC (75 MHz,
DMSO-d6) 55.7, 114.4, 129.4, 131.5, 131.7, 132.0, 151.8, 160.9; MS,
m/z: 428 (Mþ).
5a 5b
5e
5f
5g
64
32 64 256
3a 3b 3c 3e
Bacillus subtilis
Staphylococcus aureus
Escherichia coli
Pseudomonas aeruginosa
Candida albicans
*
64 128 64
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
32
*
32
32
*
128
32
32
32
*
*
*
128
*
32
64
64
32 32
32 32
4.1.13. 2,3-Di(1H-tetrazole-5-yl)-9H-indeno[2,1-b]pyrazin-9-one
(7). Yellow powder (0.28 g, yield 89%). Mp 256e258 ꢀC; [found: C,
48.95; H, 1.96; N, 43.94. C13H6N10O requires C, 49.06; H, 1.90; N,
44.01%.]; Rf (EtOAc/n-hexane, 1:1) 0.52; nmax (KBr): 3440, 1735,
Saccharomyses cerevisiae 32
*Not Active.
1601, 1570 cmꢁ1
; dH (300 MHz, DMSO-d6) 7.71e7.76 (1H, m, HeAr),
7.85e7.92 (2H, m, HeAr), 8.00e8.03 (1H, m, HeAr); dC (75 MHz,
DMSO-d6) 123.1, 125.1, 133.8, 135.6, 137.3, 139.3, 139.6, 141.4, 149.7,
154.0, 154.3, 160.1, 188.6; MS, m/z: 318 (Mþ).
(300 MHz, DMSO-d6) 2.69 (6H, s, 2CH3); dC (75 MHz, DMSO-d6)
22.2, 136.4, 153.6, 155.6; MS, m/z: 244 (Mþ).
4.1.8. 2-Ethyl-3-methyl-5,6-di(1H-tetrazole-5-yl)pyrazine
(5c). White powder (0.21 g, yield 83%). Mp 199e201 ꢀC; [found: C,
41.73; H, 3.97; N, 54.29. C9H10N10 requires C, 41.86; H, 3.90; N,
54.24%.]; Rf (EtOAc/n-hexane, 1:1) 0.45; nmax (KBr): 3456, 1568,
Acknowledgements
We gratefully acknowledge financial support from the Research
Council of Shahid Beheshti University.
1500 cmꢁ1
; dH (300 MHz, DMSO-d6) 1.31 (3H, t, J 7.1 Hz, CH3), 2.72
(3H, s, CH3), 3.02 (2H, q, J 7.1 Hz, CH2); dC (75 MHz, DMSO-d6) 11.6,
21.8, 27.6, 136.2, 136.5, 153.4, 153.5, 155, 159.1; MS, m/z: 258 (Mþ).
References and notes
4.1.9. 5-Phenyl-2,3-di(1H-tetrazole-5-yl)pyrazine (5d). White pow-
der (0.25 g, yield 85%). Mp 194e196 ꢀC; [found: C, 49.40; H, 2.82; N,
47.85.C12H8N10 requires C, 49.32; H, 2.76; N, 47.93%.]; Rf (EtOAc/n-
1. (a) Orru, R. V. A.; De Greef, M. Synthesis 2003, 1471; (b) Schreiber, S. L.
Science 2000, 287, 1964; (c) Zhu, J.; Bienayme, H. Multicomponent Reactions;
Wiley-VCH: Weinheim, Germany, 2005; (d) Domling, A. Chem. Rev. 2006,
ꢀ
106, 17.
hexane, 1:1) 0.53; nmax (KBr): 3545, 1543, 1435 cmꢁ1
; dH (300 MHz,
ꢀ
2. (a) Lieby-Muller, F.; Constantieux, T.; Jean Rodriguez, J. J. Am. Chem. Soc. 2005,
127, 17176; (b) Rivera, D. G.; Wessjohann, L. A. J. Am. Chem. Soc. 2006, 128, 7122;
(c) Chebanov, V. A.; Saraev, V. E.; Desenko, S. M.; Chernenko, V. N.; Knyazeva, I.
V.; Groth, U.; Glasnov, T. N.; Kappe, C. O. J. Org. Chem. 2008, 73, 5110; (d)
Groenendaal, B.; Vugts, D. J.; Schmitz, R. F.; de Kanter, F. J. J.; Ruijter, E.; Groen,
M. B.; Orru, R. V. A. J. Org. Chem. 2008, 73, 719; (e) Willy, B.; Muller, T. J. J. Eur. J.
Org. Chem. 2008, 4157.
DMSO-d6) 7.59e7.62 (3H, m, HeAr), 8.25e8.40 (2H, m, HeAr),
9.65e9.71 (1H, m, HeAr); dC (75 MHz, DMSO-d6) 129.6, 129.8, 131.9,
132.1, 133.8, 134.3, 137.9, 139.2, 140.5, 143.4, 145.0, 152.5; MS, m/z:
292 (Mþ).
€
3. (a) Li, J.-R.; Tao, Y.; Yu, Q.; Bu, X.-H.; Sakamoto, H.; Kitagawa, S. Chem.dEur. J.
2008, 14, 2771; (b) Wittenberger, S. J. Org. Prep. Proced. Int. 1994, 26, 499; (c)
Gaponik, P. N.; Voitekhovich, S. V.; Ivashkevich, O. A. Russ. Chem. Rev. 2006,
75, 507.
4. Smith, R. D.; Denuncia, J. V.; Lee, R. J.; Christ, D. D.; Chiu, A. T.; Carini, D. J.;
Herblin, W. F.; Timmermans, P. B. M. W. M.; Wexler, R. R. Methods Neurosci.
1993, 13, 258.
5. Katritzky, A. R.; Cai, C.; Meher, N. K. Synthesis 2007, 1204 and references cited
there in.
6. Magnus, P.; Taylor, G. M. J. Chem. Soc., Perkin Trans. 1 1991, 2657; (b) Jin, T.;
Kamijo, S.; Yamamoto, Y. Tetrahedron Lett. 2004, 45, 9435; (c) Lang, L.; Li, B.; Liu,
W.; Jiang, L.; Xu, Z.; Yin, G. Chem. Commun. 2010, 448.
7. (a) Bernstein, P. R.; Vacek, E. P. Synthesis 1987, 1133; (b) Koguro, K.; Oga, T.;
Mitsui, S.; Orita, R. Synthesis 1997, 910; (c) Larhed, M.; Hallberg, A. J. Org. Chem.
1996, 61, 9582; (d) Sauer, J.; Huisgen, R.; Strum, H. J. Tetrahedron 1960, 11, 241;
(e) Wirth, K. J.; Paehler, T.; Rosenstein, B.; Knobloch, K.; Maier, T.; Frenzel, J.;
Brendel, J.; Busch, A. E.; Bleich, M. Cardiovasc. Res. 2003, 60, 29.
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Chem., Int. Ed. 2001, 40, 2004; (b) Himo, F.; Demko, Z. P.; Noodleman, L.;
Sharpless, K. B. J. Am. Chem. Soc. 2003, 125, 9983; (d) Demko, Z. P.; Sharpless, K.
B. Angew. Chem. 2002, 114, 2214.
4.1.10. 2,3-Diphenyl-5,6-di(1H-tetrazole-5-yl)pyrazine (5e). Cream
powder (0.34 g, yield 92%). Mp 257e259 ꢀC; [found: C, 58.59; H,
3.23; N, 38.10. C18H12N10 requires C, 58.69; H, 3.28; N, 38.03%.]; Rf
(EtOAc/n-hexane, 1:1) 0.45; nmax (KBr): 3538, 1543, 1454 cmꢁ1
; dH
(300 MHz, DMSO-d6) 7.40e7.42 (6H, m, HeAr), 7.60e7.62 (4H, m,
HeAr); dC (75 MHz, DMSO-d6) 128.8, 130.2, 130.3,136.7,137.0,152.9,
153.6; MS, m/z: 368 (Mþ).
4.1.11. 2,3-Bis(4-fluorophenyl)-5,6-di(1H-tetrazole-5-yl)pyrazine
(5f). Cream powder (0.33 g, yield 81%). Mp 207e209 ꢀC; [found: C,
53.54; H, 2.44; N, 34.71. C18H10F2N10 requires C, 53.47; H, 2.49; N,
34.64%.]; Rf (EtOAc/n-hexane, 1:1) 0.51; nmax (KBr): 3538, 1543,
1454 cmꢁ1
; dH (300 MHz, DMSO-d6) 7.26e7.32 (4H, m, HeAr),
7.64e7.69 (4H, m, HeAr); dC (75 MHz, DMSO-d6) 132.5, 132.7, 132.8,
133.3, 133.4, 152.0, 153.6; MS, m/z: 404 (Mþ).
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