Silica supported lanthanum triflate mediated synthesis of 5-substituted-1H tetrazoles

Article abstract of DOI:10.1016/j.tetlet.2014.04.101

Silica supported lanthanum triflate (Ln(OTf)₃-SiO₂) promoted synthesis of 5-substituted 1H-tetrazoles via [3+2] cycloaddition between aromatic/heteroaromatic nitriles and sodium azide is a high product yielding, facile, and straightf

Full text of DOI:10.1016/j.tetlet.2014.04.101

Accepted Manuscript
Silica supported lanthanum triflate mediated synthesis of 5-substituted-1H tet-
razoles
Gangadhar A. Meshram, Shruti S. Deshpande, Pramod A. Wagh, Vipul A. Vala
PII:
S0040-4039(14)00738-2
DOI:
http://dx.doi.org/10.1016/j.tetlet.2014.04.101
TETL 44563
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
6 February 2014
29 April 2014
29 April 2014
Please cite this article as: Meshram, G.A., Deshpande, S.S., Wagh, P.A., Vala, V.A., Silica supported lanthanum
triflate mediated synthesis of 5-substituted-1H tetrazoles, Tetrahedron Letters (2014), doi: http://dx.doi.org/
10.1016/j.tetlet.2014.04.101
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Silica supported lanthanum triflate mediated
synthesis of 5-substituted-1H tetrazoles
Gangadhar Meshrama,*, Shruti Deshpandea Pramod Wagha, Vipul Amratlala
2

Tetrahedron Letters
journal homepage: www.els evier.com
Silica supported lanthanum triflate mediated synthesis of 5-substituted-1H tetrazoles
Gangadhar A. Meshrama, ∗ , Shruti S. Deshpandea, Pramod A. Wagha and Vipul A. Valaa
a
Department of Chemistry, University of Mumbai, Vidyanagari, Kalina, Santacruz (E), Mumbai- 400 098, INDIA
ARTICLE INFO
ABSTRACT
Article history:
Received
Silica supported lanthanum triflate (Ln(OTf)3- SiO2) promoted synthesis of 5-substituted 1H-
tetrazoles via [3+2] cycloaddition between aromatic/ heteroaromatic nitriles and sodium azide is
a high product yielding, facile and straightforward procedure. Non toxicity, recovery and
reusability for three continuous cycles are the noteworthy features of the currently employed
heterogeneous catalyst.
Received in revised form
Accepted
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
5-Substituted 1H-tetrazoles
Ln(OTf)3- SiO2
[3+2] cycloaddition
Nitriles
Sodium azide
∗Corresponding author. Tel.: +0-222-654-3565; fax: +91-022-265-28547; e-mail: meshramga@chem.mu.ac.in
1

Tetrazoles, rich in nitrogen content and bearing low molecular
weight, have gained wide recognition as highly versatile moiety
in organic, organometallic and medicinal chemistry. Interest in
tetrazole chemistry over the recent decade received momentum
as this functionality offers a more favorable pharmacokinetic
profile, mainly due to the widespread incorporation of tetrazole
scaffold into angiotensin II antagonist structures viz. losartan,
valsartan and BMS- 183920 etc.1 and as metabolically stable
carboxylic acid surrogates2. Tetrazoles have also been frequently
used as lipophilic spacers, ligands, precursors to a variety of
nitrogen heterocycles in coordination chemistry3,4 and in material
sciences including photography, information recording systems,
propellants and special explosives5.
comparably shorter reaction time, use of Ln(OTf)3 as a mild
lewis acid catalyst, ease of separation and reusability of the
catalyst in comparison to homogneous systems and good
generality and efficiency towards a wide of range of substrates.
In an effort to develop an innovative and efficient
heterogeneous catalytic system for [3+2] cycloaddition between
benzonitrile and sodium azide to yield 5- phenyl-1H tetrazole, we
have examined various parameters such as efficiency of the
catalyst and its reusability, effective catalyst loading, solvent and
temperature effect.
In order to get an insight into the effect of catalyst on the
yield of 5-phenyl-1H tetrazole, different silica supported Lewis
acids such as BiCl3-SiO2, Ln(OTf)3-SiO2, SbCl3-SiO2 (Table 1)
were screened. Our investigations revealed that, Ln(OTf)3-SiO2 in
Several sophisticated strategies have been posited in the
literature for the synthesis of the aforementioned molecule.
Treatment of primary amines with orthocarboxylic acid esters /
azides in presence of varied catalysts viz. imidazolium ionic
o
DMF: MeOH (4:1) at 100 C was by far the most sustainable
catalytic system that afforded the desired product in comparably
higher yields. The needfulness of the catalyst was realized, when
the controlled reaction conducted under identical conditions
devoid of Ln(OTf)3-SiO2 gave no addition product, despite
prolonged reaction time. Catalyst loading was yet another
essential factor favoring the yield of the reaction. Use of 200mg
of catalyst rendered maximum product yield of 88 % (Table 1).
Lower conversions (65- 72%) were obtained when amount of
catalyst used was 100mg to 150mg, whereas, further increase in
the amount of catalyst did not show any considerable
improvement in the yield.
7
8
liquids6, Yb(OTf)3 and In(OTf)3 yields 1-substituted tetrazoles.
[3+2] cycloaddition between organic / inorganic azides or
hydrazoic acid and corresponding nitriles produces 5-substituted
1H-tetrazoles. Numerous protocols for this conventional
synthesis includes employment of various homogenous catalytic
10
systems such as Cu2O,9 BF3.OEt2
,
Pd(OAc)2/ ZnBr2,11
Zn(OTf)3,12 AlCl3,13 Pd(PPh3)4,14 TMSN3 / TABF,15 and boron
azides.16 Much to our dismay, these typical procedures suffer
from prolonged reaction time, poor selectivity, high temperature,
toxic waste generation, separation and recovery of the catalyst,
thereby obviating the need for development of safe
heterogeneous catalytic systems. Solid support based
heterogeneous catalysts are currently under intense focus as they
are capable of driving several impracticable organic
transformations faster and under mildest possible conditions.
They seek advantages such as easy recovery and recyclability
with minimal waste generation when compared with the
conventional homogeneous catalysts. Alternatively, numerous
heterogeneous catalysts such as ZnS nanospheres,17 Cu-Zn alloy
nanopowder,18 CoY Zeolite,19 Sb2O3,20 CuFe2O4 nanoparticles,21
zeolite/ sulfated zirconia,22 CdCl2,23 phospomolybdic acid,24
FeCl3- SiO2,25 Fe2O3,26 BaWO4,27 Zn/ Al hydrotalcite,28 and
amberlyst-1529 were reported in the literature. However, high
energy barrier involved for the [3+2] cycloaddition and
sluggishness of the reaction except when potent electron
withdrawing groups are associated with the nitriles, make some
of these protocols synthetically futile necessitating more than12
hours of heating at higher temperatures. Lack of heat control and
reproducibility are amongst few drawbacks of microwave
assisted synthesis. Thus, development of highly expedient
heterogeneous catalytic system for the synthesis of 5-substitued
tetrazoles becomes essentially desirable. Lanthanide triflates,
efficient and mild Lewis acids are known to promote diverse
organic reactions including Friedel- Crafts, Baylis Hillman,
aromatic nitration, and Diels-Alder reactions in catalytic
quantities.
Table1.Effect of various reaction parameters on the formation
of tetrazoles 3a from 1aa
Entry
Catalyst
Solvent (ratio)
DMF
Yield b (%)
26c
1
BiCl3-SiO2
(100mg)
2
BiCl3-SiO2
(100mg)
SbCl3-SiO2
(100mg)
DMF:MeOH(4:1)
DMF
33
3
Traced
29
4
SbCl3-SiO2
(100mg)
DMF:MeOH(4:1)
DMF
5
Ln(OTf)3-SiO2
(100mg)
63
6
Ln(OTf)3-SiO2
(100mg)
DMF:H2O(4:1)
DMF:i-PrOH(4:1)
DMF:MeOH(4:1)
DMF:MeOH(4:1)
DMF:MeOH(4:1)
DMF:MeOH(4:1)
68
7
Ln(OTf)3-SiO2
(100mg)
Ln(OTf)3-SiO2
(100mg)
59
8
79
9
Ln(OTf)3-SiO2
(150mg)
81
10
11
Ln(OTf)3-SiO2
(200mg)
88
Ln(OTf)3-SiO2
(250mg)
85
a The reaction between 1a and sodium azide (2 equiv) was performed in the
presence of the various catalysts in 5mL solvent at 100oC for 12h.
b Isolated yield.
c& d Silica supported BiCl3 and SbCl3 were prepared by impregnating
respective catalyst (0.5mmol) on 1g silica gel (200-300 mesh).
In our zest to explore and develop synthetic protocols
involving environmentally benign and reusable heterogeneous
catalysts, we report herein silica supported Ln(OTf)3 mediated
synthesis of 5-substituted-1H tetrazole via [3+2] cycloaddition
between sodium azide and various aromatic nitriles.30 This
protocol offers several advantages over the existing methods such
as safe alternative to hazardous hydrazoic acid, higher yields in
The solvent has profound influence on the product yields. The
synergy of the combination of DMF and MeOH in the ratio 4:1
drives the transformation effortlessly to yield 88% of 5-phenyl-
1H tetrazole at 100oC (Table1). To study the varying effect of the
temperature, the reaction was initially carried out at room
temperature and then elevated to 80 oC, 100oC and 120 oC
respectively. It was explicit from Table 2 that yield of the
CN
R
N
o
reaction was considerably enhanced at 100 C. The yield remains
almost constant at further elevated temperature.
Ln(OTf)3
N
R
NaN3
+
DMF: MeOH, 100oC
NH
N
3a-3l
1a-1l
2
Scheme 1: Synthesis of 5-substiuted tetrazoles via [3+2]
cycloaddition between nitriles and sodium azide
2

Table 2. Effect of temperature on the formation of 3a from 1aa
Entry
1
2
3
4
4
5
CN
N
N
8.5
10
247-249
156-157
81
74
Temperature
Room
800C
1000C
1200C
N
temperature
N
H
1d
Yieldb
-----------
56
88
86
3d
N
CN
N
a The reaction between 1a and sodium azide (2 equiv) was performed in the
presence of Ln(OTf)3-SiO2 (200mg) in DMF:MeOH (5mL, 4:1) for 12h.
N
N
H
1e
3e
b Isolated yield.
N
CN
N
6
7
7
8
220-222
181-183
87
83
Significance of heterogeneous catalyst over the homogeneous
counterpart is its ease of separation and reusability without loss
of activity. In relevance with this, we successfully achieved the
recovery of catalyst from reaction mixture by simple filtration
and the solid residue obtained was subjected to centrifugal
N
N
H
O2
N
1f
3f
O2
N
N
CN
N
N
N
H
o
OHC
3g
washing with ethanol (2x15mL) by drying in an oven at 100 C
1g
OHC
for 3-4 hours. This assisted in keeping the catalyst surface active.
It is noteworthy, that the recycled catalyst retained optimum
activity until 4th cycle after which a drop in yield was observed.
N
CN
N
8
9
8.5
233-234
130-131
80
77
N
N
H
HO
3h
1h
CN
HO
N
Table 3. Reusability of Ln(OTf)3-SiO2in the synthesis of 3a
from 1aa
N
10.5
N
N
H
1st
2nd
3rd
4th
5th
OH
Run
3i
1i
OH
Yieldb
88
85
82
78
62
10
7.5
202-204
82
N
N
CN
a The reaction between 1a and sodium azide (2 equiv.) was performed in the
presence of Ln(OTf)3-SiO2 (200mg) in DMF:MeOH (5mL, 4:1) at 100 0C.
Br
S
Br
S
1j
3j
HN
N
N
CN
N
b Isolated yield.
N
NH
11
12
8
205-207
174-176
83
73
N
H
3k
1k
N
H
N
N
We investigated the substrate scope and generality of the
protocol by employing structurally divergent benzonitriles
bearing activating and deactivating groups and few
heteroaromatic nitriles. The methodology worked well for most
of the aromatic and heteroaromatic nitriles which gave excellent
yields over 80% and all the reactions proceeded to completion
within 7 to 10 hours. As depicted in Table 2, best percentage
conversions were obtained for nitriles with electron withdrawing
substituents viz. –NO2, -Cl, -Br as compared to electron donating
groups. Hetetroaromatics (entries 10, 11) gave respectably good
yields. Not only the nature of the substituent in benzonitrile, but
also the position of the substituent is known to affect the reaction
yield. Relatively lower yield in case of 2-hydroxy benzonitrile
(77%, entry 9) and 2-methyl benzonitrile (74%, entry 5) was
obtained in comparison with their para substituted analogues
(entries 8, 4). Low yield accompanied with longer reaction time
may be attributed to the steric hindrance by the orthosubtituents
that hampered the tetrazole formation. The current protocol was
however inefficient for benzyl nitrile and other aliphatic nitriles.
CN
N
NH
9.5
N
1l
N
3l
The reaction between various nitriles (1a-1l) and sodium azide (2 equiv.) was
performed in the presence of Ln(OTf)3-SiO2 (200mg) in DMF:MeOH (5mL,
4:1) at 1000C.
b Isolated yield.
Sharpless et al. have reported previously in the study of azide-
nitrile cycloaddition catalyzed by Zn2+, that co-ordination of the
nitrile substrate to the Lewis acidic zinc is the source of the
catalysis in the formation of 1H tetrazoles which is supported by
model calculations using density functional theory and
corroborated with experimental rate studies.31 In our case, we
suspect similar kind of interaction between Lewis acidic Ln3+
and nitriles which might promote [3+2] cycloaddition to render
5-substituted tetrazoles in excellent yields.
In conclusion, we report a facile and atom economical
synthesis of 5 substituted 1H tetrazoles from various aromatic/
heteroaromatic nitriles and sodium azide with Ln(OTf)3- SiO2 as
an effective heterogeneous catalyst. This present protocol serves
the purpose of completing the cycloaddition process in shorter
time, eliminating the hazards of direct use of hydrazoic azid,
enhancement of yield, separation and reusability of the catalyst
for four subsequent cycles with appreciably high yields. This
straightforward and simple procedure may supersede most of the
conventional procedures involving homogeneous catalytic
systems and find widespread application into organic synthesis
for preparing tetrazoles.
Table 2. Ln(OTf)3-SiO2 promoted synthesis of 5-substituted
tetrazoles 3a-3l
Entry Substrate
Product
Time
(h)
Mp (oC)
Yie
ld
(%)
N
N
CN
N
7.5
8
214-215
251-252
88
84
N
H
1
3a
1a
N
CN
N
2
N
N
H
Cl
1b
3b
Cl
CN
N
N
3
7
268-269
86
N
N
H
Br
1c
3c
Br
3

Preparation of Ln(OTf)3- SiO2 catalyst
17. Lang, L.; Li, B.; Liu, W.; Jiang, L.; Xu, Z.; Yin, G.
Chem. Commun. 2010, 46, 448.
To a solution of Ln(OTf)3 (0.5mmol) in EtOH (10mL) was
added silica gel (1g, 200-300 mesh) and stirred at room
temperature for 4-5 hours. The solvent was evaporated under
reduced pressure rendering a white free flowing powder. It was
kept under vacuum at room temperature.
18. Aridoss, G.; Laali, K. K. Eur. J. Org. Chem. 2011,
6343.
19. Rama, V.; Kanagaraj, K.; Pitchumani, K. J. Org. Chem.
2011, 76, 9090.
20. Venkateshwarlu, G.; Rajanna, K. C.; Saiprakash, P. K.
Synth. Commun. 2009, 39, 426.
Acknowledgments
21. Sreedhar, B.; Suresh Kumar, A.; Yada, D. Tetrahedron
Lett. 2011, 52, 3565.
The authors are thankful to the Department of Chemistry,
University of Mumbai, and Micro-analytical laboratory for
technical assistance.
22. Teimouri, A.; Chermahini, A. N.; Polyhedron, 2011,
30, 2606.
23. Venkateshwarlu, G.; Premlatha, A.; Rajanna, K. C.;
Saiprakash, P. K. Synth. Commun. 2009, 39, 4479.
24. Takale, S.; Manave, S.; Phatangare, K.; Padalkar, V.;
darvatkar, N.; Chaskar, A. Synth. Commun. 2012, 42,
2375.
References and notes
1. (a) Smith, R. D.; Dunica, 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; (b) Chiu, A. T.; Dunica, J. V.; McCall, D. E.;
Wong, P. C.; Price, W. A., Jr.; Thoolen, M. J. M. C.;
Carini, D. J.; Johnson, A. L.; Timmermans, P. B. M. W.
M. J. Pharmacol. Exp. Ther. 1989, 250, 867; (c)
Buehlmayer, P.; Criscione, L.; Fuhrer, W.; Furet, P.;
DeGasparo, M.; Stutz, S.; Whitebread, S. J. Med.
Chem. 1991, 34, 3105.
25. Nasrollahzadeh, M.; Bayat, Y.; Habibi, D.; Moshaee, S.
Tetraheron Lett. 2009, 50, 4435.
26. Qi, G.; Dai, Y. Chin. Chem. Lett. 2010, 21, 1029.
27. He, J.; Li, B.; Chen, F.; Xu, Z.; Yin, G. J. Mol. Catal.
A. 2009, 304, 135.
28. Lakshmi Kantam, M.; Shiv Kumar, K. B.; Phani Raja,
K. J. Mol. Catal. A. 2006, 247, 186.
29. Shelkar, R.; Singh, A.; Nagarkar, J. Tetrahedron Lett.
2013, 54, 106.
2. Myznikov, L. V.; Hrabalek, A.; Koldobskii, G. I. Chem.
Heterocycl. Compd. 2007, 43, 1.
3. Huisgen, R.; Sauer, J.; Sturn, H. J.; Markgraf, J. H.
Chem. Ber. 1960, 93, 2106.
30. Typical procedure for the synthesis of 5-phenyl-1H-
tetrazole
4. Moderhack, D. J.; Prakt. Chem. 1988, 340, 687.
5. (a) Brown, M. U.S. Patent 3,338,915, 1967; Chem.
Abstr. 1968, 87299.; (b) Ostrovskii, V. A.; Pevzner, M.
S.; Kofmna, T. P.; Shcherbinin, M. B.; Tselinskii, I. V.
Targets Heterocycl. Syst. 1999, 3, 467; (c) koldobskii,
G. I.; Otrovskii, V. A. Usp. Khim. 1994, 63, 847.
6. Dighe, S. N.; Jain, K. S.; Srinivasan, K. V. Tetrahedron
Lett. 2009, 50, 6139.
A mixture of benzonitrile (1mmol), sodium azide
(2mmol), Ln(OTf)3- SiO2 (200mg) and DMF: MeOH (
4:1, 5mL) in a pressure vial was initially stirred at
room temperature. After 30 min, the temperature of the
o
reaction mixture was raised to 100 C and stirred for
another 7 hours. After consumption of 1a (as indicated
by TLC), the catalyst was separated by filtration and the
filtrate was treated with ethyl acetate (15mL). The
organic layer was washed with 4N HCl (20mL). The
resultant organic layer was separated and the aqueous
layer was extracted with ethyl acetate (15mL). The
combined organic layer was washed with water (2 x
10mL), dried over anhydrous sodium sulphate and
concentrated to afford white crystalline solid.
7. Su, W.; Hong, Z.; Shan, W.; Zhang, X. Eur. J. Org.
Chem. 2006, 2723.
8. Kundu, D.; Majee, A.;Hajra, A. Tetrahedron Lett. 2009,
50, 2668.
9. Jin, T.; Kitahara, F.; Kamjio, S.; Yamamoto, Y.
Tetrahedron Lett. 2008, 49, 2824
5-phenyl-1H tetrazole(3a)
IR (KBr, cm-1): 3331, 2907, 2850, 2611,
1607, 1485, 1433, 1050, 828, 742. 1 H NMR
(300 MHz, CDCl3): 8.04 8.007 (m, 1H),
7.611- 7. 574 (m, 2H). 1 3 C NMR (75 MHz,
CDCl3): 156.03, 131.19, 129.08, 126.805,
123.924. MS: m/z = 146 [M]+.
10. Kumar, A.; Narayanan, R.; Shechter, H. J. Org. Chem.
1996, 61, 4462.
11. Yizhong, Z.; Yiming, R.; Chun, C. Helv. Chim. Acta
2009, 92, 171.
12. Hajra, S.; Sinha, D.; Bhowmick, M. J.Org. Chem. 2007,
72, 1852.
31. Himo, F.; Demko, Z. P.; Noodleman, L.; Sharpless, K.
B. J. Am. Chem. Soc. 2003, 125, 9983.
13. Matthews, D. P.; Green, J. E.; Shuker, A. J. J. Comb.
Chem. 2000, 2, 19.
14. Gyoung, Y. S.; Shim, J. G.; Yamamoto, Y. Tetrahedron
Lett. 2000, 41, 4193.
15. Amantini, D.; Beleggia, R.; Fringuelli, F.; pizzo, F.;
Vaccoro, L. J. Org. Chem. 2004, 69, 2896.
16. Yao, Y.; Zhou, Y.; Lin, B.; Yao, C. Tetrahedron Lett.
2013, 54, 6779.
4

CN
R
N
Ln(OTf)3
N
R
NaN3
+
DMF: MeOH, 100oC
NH
N
3a-3l
1a-1l
2
Scheme 1: Synthesis of 5-substiuted tetrazoles via [3+2] cycloaddition between nitriles and sodium azide
5

Table1.Effect of various reaction parameters on the formation of tetrazoles 3a from 1aa
Entry
Catalyst
Solvent (ratio)
Yield b (%)
1
BiCl3-SiO2
(100mg)
DMF
26c
2
BiCl3-SiO2
(100mg)
DMF:MeOH(4:1)
DMF
33
3
SbCl3-SiO2
(100mg)
Traced
29
4
SbCl3-SiO2
(100mg)
DMF:MeOH(4:1)
DMF
5
Ln(OTf)3-SiO2
(100mg)
63
6
Ln(OTf)3-SiO2
(100mg)
DMF:H2O(4:1)
DMF: i-PrOH(4:1)
DMF:MeOH(4:1)
DMF:MeOH(4:1)
DMF:MeOH(4:1)
DMF:MeOH(4:1)
68
7
Ln(OTf)3-SiO2
(100mg)
Ln(OTf)3-SiO2
(100mg)
59
8
79
9
Ln(OTf)3-SiO2
(150mg)
81
10
11
Ln(OTf)3-SiO2
(200mg)
Ln(OTf)3-SiO2
(250mg)
88
85
a The reaction between 1a and sodium azide (2 equiv) was performed in the presence of the various catalysts in 5mL solvent at 100oC for
12h.
b Isolated yield.
c& d Silica supported BiCl3 and SbCl3 were prepared by impregnating respective catalyst (0.5mmol) on 1g silica gel (200-300 mesh).
Table2. Effect of temperature on the formation of 3a from 1aa
Entry
1
2
3
4
Temperature
Room
800C
1000C
1200C
temperature
Yieldb
-----------
56
88
86
a The reaction between 1a and sodium azide (2 equiv) was performed in the presence of Ln(OTf)3-SiO2 (200mg) in DMF:MeOH (5mL, 4:1)
for 12h.
b Isolated yield.
Table3. Reusability of Ln(OTf)3-SiO2in the synthesis of 3a from 1aa
Run
1st
2nd
3rd
4th
5th
Yieldb
88
85
82
78
62
a The reaction between 1a and sodium azide (2 equiv) was performed in the presence of Ln(OTf)3-SiO2 (200mg) in DMF:MeOH (5mL, 4:1)
at 1000C.
b Isolated yield.
Table4.Ln(OTf)3-SiO2 promoted synthesis of 5-substituted tetrazoles 3a-3l
Entr
y
Substrate
Product
Tim
e (h)
Mp (oC)
214-215
251-252
Yiel
d
(%)
N
N
CN
N
7.5
8
88
84
1
2
N
H
3a
1a
N
CN
N
N
N
H
Cl
1b
Cl
6

CN
N
N
3
7
268-269
86
N
N
H
Br
1c
3c
Br
CN
N
N
4
5
8.5
10
247-249
156-157
81
74
N
N
H
3d
1d
N
CN
N
N
N
H
1e
3e
N
CN
N
6
7
7
8
220-222
181-183
87
83
N
N
H
O2N
1f
3f
O2N
N
CN
N
N
N
H
OHC
3g
1g
OHC
N
CN
N
8
9
8.5
233-234
130-131
80
77
N
N
H
HO
3h
1h
CN
HO
N
N
10.5
N
N
H
OH
3i
1i
OH
10
11
7.5
8
202-204
205-207
82
83
N
N
CN
Br
S
Br
S
1j
3j
HN
N
N
N
CN
N
NH
N
H
3k
1k
N
H
N
N
CN
N
NH
12
9.5
174-176
73
N
1l
N
3l
The reaction between various nitriles (1a-1l) and sodium azide (2 equiv.) was performed in the presence of Ln(OTf)3-SiO2 (200mg) in
DMF:MeOH (5mL, 4:1) at 1000C.
b Isolated yield.
7