Mesoporous AlPO4: A highly efficient heterogeneous catalyst for synthesis of 5-substituted 1H-tetrazoles from nitriles and sodium azide via [3 + 2] cycloaddition

Article abstract of DOI:10.1246/cl.2012.814

The mesoporous AlPO₄ with high surface area and fine mesoporous structure was prepared by a soft template method and showed excellent catalytic performance for synthesis of 5-substituted 1H-tetrazoles from various nitriles and sodium azide with

Full text of DOI:10.1246/cl.2012.814

doi:10.1246/cl.2012.814
814
Published on the web August 1, 2012
Mesoporous AlPO4: A Highly Efficient Heterogeneous Catalyst
for Synthesis of 5-Substituted 1H-Tetrazoles from Nitriles
and Sodium Azide via [3 + 2] Cycloaddition
Man Ai,1,2 Leiming Lang,1,2 Baojun Li,1,2 and Zheng Xu*1,2
1State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering,
Nanjing University, Nanjing 210093, P. R. China
2Nanjing National Laboratory of Microstructure, School of Chemistry and Chemical Engineering,
Nanjing University, Nanjing 210093, P. R. China
(Received March 30, 2012; CL-120272; E-mail: zhengxu@nju.edu.cn)
The mesoporous AlPO4 with high surface area and fine
mesoporous structure was prepared by a soft template method
and showed excellent catalytic performance for synthesis of
5-substituted 1H-tetrazoles from various nitriles and sodium
azide with excellent yields (91%-98%). The heterogeneous
AlPO4 catalyst is a good candidate to substitute metal salts or
other heterogeneous catalyst and has potential value for industry
application.
In the nearest decades, research on tetrazoles has been
attracting great attention, due to its wide applications,1 such as
metabolically stable surrogates for carboxylic acid,2 lipophilic
spacers in pharmaceuticals, as well as special explosive and
information recording systems in material science.3
The most conventional way to synthesize 5-substituted 1H-
tetrazoles is via [3 + 2] cycloaddition of nitriles and sodium
azides.4 However new challenges have arisen since the use of
strong Lewis acids or expensive and toxic metals may lead to the
production of hydrazoic acid.5 Recently, several new catalytic
systems have been developed to overcome these disadvantages.
Jursic and his colleagues have effectively synthesized
5-substituted 1H-tetrazoles with TMSN3 and TBAF instead of
metal salts in micellar media.6 The same method was also carrid
out by Pizzo and co-workers under solvent-free conditions.7a
Sharpless and co-workers reported a safer and more convenient
method for this reaction using a stoichiometric amount of Zn(II)
salts in water.7b,7c
Although those homogeneous catalysts exhibit excellent
activity in the reaction, the separation and recovery of the
catalyst is still a big challenge. In this concern, novel
heterogeneous catalysts are urgently needed. Currently several
heterogeneous catalysts were reported for the synthesis of
5-substituted 1H-tetrazoles in DMF, including Zn/Al hydro-
talcite,8a nanocrystalline ZnO,8b or Cu2O.8c In recent years, great
interest has been focused on the study of novel heterogeneous
catalysts in our group. Previously, we have synthesized the
tetrazoles with high yields in heterogeneous catalytic systems
using tungstate salts9a and mesoporous ZnS9b as catalyst. In
this paper, mesoporous AlPO4 (MA) was reported as a new
heterogeneous catalyst with large surface area for the synthesis
of 5-substituted 1H-tetrazoles from nitriles and sodium azide in
DMF.
Figure 1. (a), (b) TEM images of mesoporous AlPO4.
(c) XRD pattern in small-angle region and (d) N2 adsorption-
desorption isotherms at 77 K, the inset is the pore size
distribution of mesoporous AlPO4.
of MA shows diffraction peaks and their relative intensities are
in good agreement with the standard XRD pattern of AlPO4
(JCPDS: 760234), which shows that the synthesized product is
high purity AlPO4. TEM images of the MA (Figures 1a and 1b)
indicated that the catalyst exhibited worm-like mesoporous
structures, which well agreed with the XRD at small angle
(Figure 1c). As we all know, the surface area and pore structure
of a catalyst are important for catalytic activity. The mesoporous
structure can provide larger BET surface area and more active
sites, which can improve the catalytic activity. N2 adsorption-
desorption isotherms showed that AlPO4 presented large BET
surface area (370 m2 g¹1) (Figure 1d). The pore size distribution
(inset of Figure 1d) showed the evidence of narrow uniform
pore with about 10 nm pore diameter.
In order to get optimum conditions for the reaction, the
amount of MA catalyst, the reaction temperature and time,
and the solvent were evaluated. The results are summarized in
Table 1, including yields, turnover numbers (TON), and turn-
over frequency (TOF). Entry 1 in Table 1 shows that no reaction
occurred without MA catalyst while 5-phenyltetrazole can be
obtained in 92% yield when 0.1 g of MA was added as catalyst
(Table 1, Entry 2). Further increasing the amount of MA
The mesoporous AlPO4 was prepared by a soft template
method in ethanol solution containing P123, H3PO4, and AlCl3,
following aging and calcination (see SI).10 XRD (Figure S1)10
Chem. Lett. 2012, 41, 814-816
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

815
Table 1. Catalytic performance of MA under various reaction
Table 2. Preparation of 5-substituted 1H-tetrazoles with vari-
ous aluminum catalystsa
parametersa
Catal.
/g
t
T
Yield
TON
TOF
Yield
/%c
TON
/mol mol
TOF
/10¹3 © h
Catalystb
Entry
Solvent
Entry
¹1
¹1
/%b /mol mol /10¹3 © h
¹1
¹1
/h /°C
d
1
2
3
4
0
0.1
0.2
12 120 DMF
12 120 DMF
12 120 DMF
0
92
95
76
90
94
96
65
82
0
0
234
121
386
229
143
61
165
208
221
206
1
2
3
4
5
6
7
AlPO4
AlCl3
77
78
82
35
7.8
0
2.349
2.379
2.501
1.068
0.2379
0
196
198
208
88.9
19.8
0
2.806
1.449
4.636
2.745
2.867
2.928
1.983
2.501
2.653
2.471
Al2(SO4)3
Al(OH)3
£-Al2O3
Na3PO4
Al
0.05 12 120 DMF
5c 1.0
12 120 DMF
24 120 DMF
48 120 DMF
12 100 DMF
12 140 DMF
6
7
8
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0
0
0
aReaction conditions: benzonitrile (2.5 mmol), NaN3 (2.6
9
b
mmol), DMF (5 mL), reaction time 12 h, 120 °C. Amount of
10
11
12
13
12 120 DMSO 87
Al3+ used is equivalent to that of 0.1 g of AlPO4. Isolated
c
12 120 NMP
12 120 H2O
12 120 DMF
81
Trace
85d
yields (average of two runs). dPrepared by precipitation
method.
2.59
216
aReaction conditions: benzonitrile (2.5 mmol), MA (0.1 g), and
NaN3 (2.6 mmol) were stirred in 5 mL of DMF for 12 h at
120 °C. bIsolated yield (average of two runs). cReaction
conditions: benzonitrile (25 mmol), MA (1.0 g), and NaN3
(26 mmol) were stirred in 50 mL of DMF for 12 h at 120 °C.
dYield for the third time use.
Table 3. The synthesis of 5-substituted 1H-tetrazole with
AlPO4 under various substratesa
H
R
N
R
N
N
AlPO4
DMF
NaN3
CN
+
N
Starting
material
Yield
TON
TOF
Entry
1
Product
/%b /mol mol–1 /10–3 × h–1
(Table 1, Entry 3) or amplifying 10 times the amount of the raw
materials (Table 1, Entry 5), has no significant change for the
yield of 5-phenyltetrazole, whereas decreasing the amount of
MA leads to decrease the yield a lot (Table 1, Entry 4). Entries
2, 6, and 7 in Table 1 show the optimum reaction time for the
reaction is 12 h, further extended reaction time has little effect on
the reaction yield. The optimum reaction temperature is 120 °C,
either decreasing or increasing the reaction temperature has an
unfavorable influence on the reaction (Table 1, Entries 2, 8, and
9). In addition, the solvent also played a remarkable role
(Table 1, Entries 2 and 10-12). The experimental results show
that DMF, DMSO, and NMP are good solvent with 92%, 87%,
and 81% yields, respectively, under the optimum conditions.
Among them, DMF is more preferable, whereas water is not
suitable for the reaction (Table 1, Entry 12). Comprehensively,
the optimum reaction conditions for synthesis of 5-phenyl-
tetrazole are as follows: 0.1 g of MA as catalyst, reacting for
12 h, reaction temperature 120 °C, and DMF as solvent. The
recycle experiments show that the MA exhibits a good reused
performance and reaction yield still remain 85% after reuse for
the third time (Table 1, Entry 13). It indicates that the prepared
MA is quite stable in the reaction process with good recycla-
bility which is crucial for industrial application.
In order to evaluate the catalytic performance of the MA, a
series of aluminum salts and oxide and various benzonitrile
derivatives as the starting materials were tested under the
optimum reaction conditions. The results are listed in Table 2.
Compared with the MA, AlPO4 prepared by precipitation with
low BET surface area (21 m2 g¹1, Figure S2)10 exhibits relatively
low catalytic activity (Table 2, Entry 1). AlCl3 and Al2(SO4)3
exhibited moderate catalytic performance (Table 2, Entries 2
and 3), while Al(OH)3 and £-Al2O3 showed lower catalytic
capability than AlPO4 (Table 2, Entries 4 and 5). Using Na3PO4
as a catalyst, no detectable reaction takes place, indicating that
92
82
2.806
2.501
234
208
2
3
93
2.836
237
4
5
6
90
75
2.745
2.288
229
191
88
2.684
221
7
8
9
87
90
2.654
2.745
221
229
91
2.776
231
10
11
89
98
2.715
2.989
226
249
aReaction conditions: benzonitrile derivative (2.5 mmol), NaN3
(2.6 mmol), AlPO4 (0.1 g), DMF (5 mL), reaction time 12 h,
b
120 °C. Isolated yields (average of two runs).
Chem. Lett. 2012, 41, 814-816
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

816
the catalytic active component of AlPO4 is Al3+ rather than
PO4 (Table 2, Entry 6). Using aluminum metal as a catalyst,
17, 151. c) D. Moderhack, J. Prakt. Chem./Chem.-Ztg.
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3¹
also no catalytic reaction can be observed, which further
indicates that the catalytic active species is Al3+ but not the
neutral aluminum atom (Table 2, Entry 7). All these results
indicate that the MA is a promising highly active catalyst, which
not only exhibits unique catalytic performance, but also is easily
separated and reused.
Furthermore, various benzonitrile derivatives were used as
the starting materials and the results are listed in Table 3.
Although the reaction yields for various benzonitrile derivatives
are all over 75%, the substituent effect still can be seen on the
reaction. As shown in Table 3, the electron-donating substituent
is of great advantage to the reaction and the pyridol nitrile is
most favorable one, while the NO2-group is harmful for the
reaction.
In summary, we demonstrated that the mesoporous AlPO4
with high surface area and fine mesoporous structure exhibits
excellent catalytic performance for the synthesis of 5-substituted
1H-tetrazoles. Also as a heterogeneous catalyst, the mesoporous
AlPO4 exhibits an excellent recoverability and ease of reusage
which is crucial for industrial application.
2
3
4
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6
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We acknowledge the financial support from the National
Natural Science Foundation of China under the Major Research
Project (No. 2007CB936302).
a) J. He, B. Li, F. Chen, Z. Xu, G. Yin, J. Mol. Catal. A:
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10 Supporting Information is available electronically on the
CSJ-Journal Web site, http://www.csj.jp/journals/chem-lett/
index.html.
Chem. Lett. 2012, 41, 814-816
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/