A one-pot pseudo nine-component isocyanide-based reaction: Synthesis of a new class of zinc 1,5-disubstituted 1H-tetrazol-5-yl coordination complexes

Article abstract of DOI:10.1016/j.tetlet.2011.06.017

A novel one-pot pseudo nine-component synthesis of zinc 1,5-disubstituted 1H-tetrazol-5-yl coordination complexes in good yields starting from simple and readily available substrates, including a 1,3-dicarbonyl compound, an isocyanide, N,N-dimethylformami

Full text of DOI:10.1016/j.tetlet.2011.06.017

Tetrahedron Letters 52 (2011) 4388–4391
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A one-pot pseudo nine-component isocyanide-based reaction: synthesis of
a new class of zinc 1,5-disubstituted 1H-tetrazol-5-yl coordination complexes
a,
⇑
a
a
a
b
Ahmad Shaabani , Mojtaba Mahyari , Mozhdeh Seyyedhamzeh , Sajjad Keshipour , Seik Weng Ng
a
Department of Chemistry, Shahid Beheshti University G.C., PO Box 19396-4716, Tehran, Iran
Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia
b
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel one-pot pseudo nine-component synthesis of zinc 1,5-disubstituted 1H-tetrazol-5-yl coordina-
tion complexes in good yields starting from simple and readily available substrates, including a 1,3-dicar-
bonyl compound, an isocyanide, N,N-dimethylformamide dimethyl acetal, sodium azide, and zinc
chloride in methanol at ambient temperature, is described.
Received 17 April 2011
Revised 22 May 2011
Accepted 3 June 2011
Available online 13 June 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Zinc tetrazole coordination complex
Tetrazole
Isocyanide
Multi-component
Azide
Recently a new area in tetrazole chemistry has been developed
which overlaps at the border with inorganic chemistry. Tetrazoles
which contain four electron-donating atoms in the five-membered
ring are able to coordinate to metals through different nitrogen
atoms via a covalent, ionic, or coordination bond which has led
and nitrile compounds with metal salts. Among heterocyclization
reactions for the synthesis of tetrazoles, [3+2] cycloadditions of
azides to nitriles in the presence of metal salts are the most signif-
1
–3,33
icant.
Zinc(II) is a common metal ion in the human body and is in-
volved in various biological activities, such as cellular processes,
including cell proliferation, reproduction, immune function, and
1–3
to diversity in metal-tetrazole derivatives (MTs).
It is interesting to note, that to date, numerous metal-tetrazole
coordination complexes have been synthesized. MTs are useful
coordinate compounds and are used in a wide range of applications
in many research fields. A key application of MTs is in organic syn-
thesis where they are used as starting and intermediate com-
pounds for the synthesis of N-substituted tetrazoles from various
3
4
defense against free radicals, and plays an important role in both
3
5
genetic stability and functionality. Tetrazole metal derivatives
exhibit various applications and demonstrate interesting coordina-
3
6
tion chemistry.
Isocyanide-based multicomponent reactions (IMCRs) are pow-
erful approaches to access numerous highly functionalized hetero-
cyclic molecules from readily available starting materials. In
1
–9
metal tetrazolates.
The ability of tetrazoles to form stable com-
plexes with various metal ions is used widely in photoprocesses,
1
0–14
15
37
corrosion protection of metals,
energetic compositions,
continuation of our previous work on IMCRs, and inspired by
1
6
17
38
pyrotechnics, semiconductor nanoparticles, ultra-low-density
nanostructured metal foams, gas storage, and heterogeneous
Ugi tetrazole reactions, attempts have been made to develop a
18
new route for the synthesis of zinc 1,5-disubstituted 1H-tetrazol-
5-yl compounds. The products were prepared via a one-pot process
involving a pseudo nine-component condensation reaction of var-
ious cyclic 1,3-dicarbonyl compounds 1, DMF-DMA (2), isocya-
nides 3, and sodium azide with zinc chloride in methanol
without using any catalyst or activation methods (Scheme 1).
The advantage of the IMCR strategy was the ability to assemble
the desired product in one step, in contrast to the classic method
which requires the use of more than one step. In addition, this
strategy was shown to be environmentally friendly and highly effi-
cient in that there was no need for ligand synthesis.
1
9
catalysis. For example, iron(III) complexes I and II showed high
efficiency as catalysts in the oxidation of olefins (Fig. 1).20
Methods for the synthesis of MTs can be divided into two strat-
egies. The first involves the reaction of five-substituted tetrazoles
with metal salts in the presence of bases, such as metal hydrox-
5
,21–25
26–29,6,30,31
5,32
ides,
alkoxides
, or hydrides
to afford tetrazo-
lates. The second route comprises heterocyclizations of azide ions
⇑
Corresponding author. Fax: +98 21 22403041.
E-mail address: a-shaabani@cc.sbu.ac.ir (A. Shaabani).
0
040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.06.017

A. Shaabani et al. / Tetrahedron Letters 52 (2011) 4388–4391
4389
R2
The reaction proceeded very efficiently under mild reaction
conditions at ambient temperature to produce the corresponding
products 5a–e in good yields (Fig. 2).
R1
R3
N
N
O
N
N
N
N
The structures of compounds 5a–e were deduced from their IR,
R1
N
N
Fe
R3
R2
1
13
O
mass, H and C NMR spectral data. The structure of 5a was also
determined by single crystal X-ray analysis. The ORTEP diagram
of 5a shows that two of the four-component products coordinated
to zinc and resulted in the formation an octahedral complex
O
R2
N
N
R3
N
N
R1
(
Fig. 3).
It is conceivable that the initial event is the formation of inter-
mediate 6 from condensation between the 1,3-dicarbonyl com-
1
i
2
3
1
t
2
3
R = Bu, R = CN, R = OMe (I); R = Bu, R = H, R = Ph (II)
Figure 1.
3
9
pound and DMF-DMA.
Then, on the basis of the well-
,b-
established reaction of isocyanides with electron-deficient
a
4
0
In a pilot experiment, dimedone (1a) and DMF-DMA (2) were
stirred in the absence of solvent for 1 h at ambient temperature.
After completion of the condensation reaction (monitored by
TLC),3 cyclohexylisocyanide (3a), sodium azide, and zinc chloride
were added to the reaction vessel along with methanol as the sol-
vent, and the contents stirred for 6 h. The progress of the reaction
was monitored by TLC. After completion of the reaction, the prod-
uct 5a was obtained in 83% yield.
To evaluate the use of this interesting approach, a variety of cyc-
lic and acyclic 1,3-dicarbonyl compounds and isocyanides were
examined, however, we were only able to obtain five of these prod-
ucts. The results are summarized in Table 1.
unsaturated carbonyl compounds, compound 6 coordinates with
Zn(II) and undergoes a Michael-type addition with the isocyanide
to produce intermediate 8. Next, nucleophilic attack of an azide
ion on the nitrilium moiety followed by 1,5-dipolar cycloaddition
9
4
1,42
produces intermediate 9.
Intermediate 9 can then be converted
into complex 10. It is highly possible that this species coordinates
to intermediate 6 which undergoes a second identical process. Fi-
nally, zinc retains its coordination to these ligands and produces
octahedral complexes 5a–e of zinc (Scheme 2).
In conclusion, from simple and readily available substrates un-
der mild reaction conditions using an IMCR strategy, we have
developed a pseudo nine-component isocyanide-based reaction
O
N
solvent-free
h, rt
MeOH
NaN3
ZnCl2
1
O
3
1
2
6
5
Scheme 1. Synthesis of zinc 1,5-disubstituted 1H-tetrazol-5-yl complexes 5a–e.
Table 1
Synthesis of zinc 1,5-disubstituted 1H-tetrazol-5-yl coordination complexes 5a–e
Entry
1,3-Dicarbonyl 1
R
Product
Time (h)
Yield (%)
1
2
3
4
5
Dimedone
Cy
Cy
Cy
5a
5b
5c
5d
5e
7
8
7
7.5
6.5
83
76
80
79
75
1,3-Cyclohexanedione
1,3-Cyclopentanedione
Dimedone
1,1,3,3-Tetramethylbutyl
t
1,3-Cyclopentanedione
Bu
N
O
Zn
O
N
N
O
N
O
N
N
N
N
N
O
Zn
N
N
O
Zn
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
O
O
N
O
N
N
N
O
O
O
5a
5b
5c
N
O
Zn
O
N
N
N
O
Zn
O
N
N
N
N
N
N
N
N
N
N
N
N
O
N
N
O
N
N
O
O
5d
5e
Figure 2. The structures of products 5a–e.

4
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A. Shaabani et al. / Tetrahedron Letters 52 (2011) 4388–4391
Figure 3. ORTEP diagram of 5a.
N
N
+
2+
2+
N
N
R
R
N
O
Zn
Zn
N
N
O
N
N
Zn
O
O
O
N
O
O
O
O
N Na+
N
Zn2+
O
N
O
C
N
R
O
3
1
2
8
6
7
N
+
+
+
N
N
N
N
N
R
N
N
N
N
R
N
O
R
N
R
N
O
N
O
O
1) 6
2) 3
3) NaN
Zn
N
Zn
N
N
Zn
N
N
Zn
N
N
3
O
O
O
O
N
N
O
N
N
O
R
5
a-f
10
9
Scheme 2. The proposed mechanism for the formation of complexes 5.
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reaction conditions without using any catalyst or activation meth-
ods. The complexes were obtained in good yield, and product iso-
lation was very straightforward. This approach may be useful to
chemists seeking novel synthetic fragments with unique proper-
ties for medicinal chemistry programs. Further studies and syn-
thetic applications of this chemistry are in progress in our
laboratory.
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Acknowledgment
We gratefully acknowledge the financial support from the Re-
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Supplementary data
Supplementary data associated with this article can be found, in
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