Highly efficient synthesis of 5-substituted 1H-tetrazoles catalyzed by Cu-Zn alloy nanopowder, conversion into 1,5- and 2,5-disubstituted tetrazoles, and synthesis and NMR studies of new tetrazolium ionic liquids

Article abstract of DOI:10.1002/ejoc.201100957

A series of 5-substituted 1H-tetrazoles were synthesized through [3+2] cycloaddition reactions between nitriles RCN and NaN₃ in the presence of Cu-Zn alloy nanopowder as catalyst. The 1,5-dibutyl, 1-butyl-5-hexyl, 2,5-dibutyl, and 2-butyl-5-hexyl derivatives were then used as building blocks to synthesize several novel tetrazolium ionic liquids (ILs) with EtSO ₄^-, OTf^-, and NTf₂^- counterions. Whereas alkylation of the 2,5-dialkyltetrazoles selectively gave the N-4 alkylated onium salts, with the 1,5-dialkyl derivatives approximately 1:1 mixtures of two tetrazolium salts were formed by alkylation at N-3 and N-4. The triflate and ethyl sulfate salts are room-temperature ILs that are hydrophilic, whereas the NTf₂ salts are low-melting ILs and are hydrophobic. The resulting tetrazolium-based ionic liquids were studied by various multinuclear and 2D NMR techniques including natural abundance ¹⁵N and ¹H/¹⁵N correlations.

Full text of DOI:10.1002/ejoc.201100957

FULL PAPER
DOI: 10.1002/ejoc.201100957
Highly Efficient Synthesis of 5-Substituted 1H-Tetrazoles Catalyzed by Cu–Zn
Alloy Nanopowder, Conversion into 1,5- and 2,5-Disubstituted Tetrazoles, and
Synthesis and NMR Studies of New Tetrazolium Ionic Liquids
Gopalakrishnan Aridoss[a] and Kenneth K. Laali*[a]
Keywords: 1H-Tetrazole synthesis / Cu/Zn alloy nanopowder / Cycloaddition / Ionic liquids / 15N NMR spectroscopy
A series of 5-substituted 1H-tetrazoles were synthesized
through [3+2] cycloaddition reactions between nitriles RCN
and NaN3 in the presence of Cu–Zn alloy nanopowder as
catalyst. The 1,5-dibutyl, 1-butyl-5-hexyl, 2,5-dibutyl, and 2-
butyl-5-hexyl derivatives were then used as building blocks
to synthesize several novel tetrazolium ionic liquids (ILs) with
onium salts, with the 1,5-dialkyl derivatives approximately
1:1 mixtures of two tetrazolium salts were formed by alky-
lation at N-3 and N-4. The triflate and ethyl sulfate salts are
room-temperature ILs that are hydrophilic, whereas the NTf2
salts are low-melting ILs and are hydrophobic. The resulting
tetrazolium-based ionic liquids were studied by various mul-
tinuclear and 2D NMR techniques including natural abun-
–
EtSO4–, OTf–, and NTf2 counterions. Whereas alkylation of
1
the 2,5-dialkyltetrazoles selectively gave the N-4 alkylated
dance 15N and H/15N correlations.
Introduction
TMSN3/iron salts/DMF,[10] and NaN3/mesoporous ZnS
nanospheres/HCl/DMF systems.[11] Application of a scal-
able high-temperature microreactor for the synthesis of 5-
substituted 1H-tetrazoles in either a batch or a continuous
flow system utilizing NaN3/AcOH has also been re-
ported.[12]
Although copper- and zinc-based molecular catalysts
have been employed for decades in a wide variety of organic
transformations, there has been intense recent research
interest in their more efficient application in the nanopartic-
ulate forms.[11,13] The utility of bimetallic catalysts has been
demonstrated in important transformations such as
Ullmann reactions (Cu–Zn nanocatalyst),[14] propar-
gylation of ketones (Cu–Zn couple),[15] industrial methanol
synthesis (ZnO supported Cu),[16] and in certain cross-cou-
pling reactions (Cu–Ni–C).[17] The potential for synergic ef-
fects between two metals led us to explore the efficacy of
bimetallic Cu–Zn nanoparticles in [3+2] cycloaddition reac-
tions between nitriles and azides for the construction of 5-
substituted 1H-tetrazoles.
In this two-part study we first report on a convenient,
high-yielding synthesis of a host of 5-substituted 1H-tetra-
zoles through the employment of commercially available,
cheap, Cu–Zn alloy nanopowder. This procedure offers easy
product isolation and reuse of the catalyst. In the second
part we report on the synthesis and characterization of a
series of new tetrazole-based onium salts with OTf, EtSO4,
and NTf2 counterions as room-temperature or low-melting
ionic liquids.
The 1H-tetrazole functional group is recognized as a
highly versatile moiety in organic, organometallic, and me-
dicinal chemistry.[1] With a high nitrogen content and low
molecular weight, the tetrazole moiety – in particular its
amino and nitro derivatives, and their derived onium salts –
have become interesting targets for possible application in
high-energy chemistry.[2]
Various methods for the synthesis both of 5-substituted
and of 1-substituted 1H-tetrazoles have been developed.
For the 1-substituted systems, treatment of primary amines
with orthocarboxylic acid ester/sodium azide and employ-
ment of metallic triflates or imidazolium ionic liquids (ILs)
are among the more recently reported methods.[3] In a re-
cent study from this laboratory[4] we reported on the use of
orthocarboxylic acid esters/TMSN3 in Brønsted acidic
ILs – namely [EtNH3][NO3] and [PMIM(SO3H)][OTf] – for
the facile construction of 1-substituted 1H-1,2,3,4-tetra-
zoles, with recycling and reuse of the ILs. [3+2] Cycload-
ditions between nitriles and azides constitute an efficient
and widely used preparative method for the construction of
5-substituted-1H-tetrazoles. Since the 2001 paper by
Demko and Sharpless on the use of NaN3/ZnBr2 in water,[5]
several other preparative methods have been reported.
These include TMSN3/TBAF/solventless,[6] NaN3/Zn/Al
hydrotalcite/DMF,[7]
TMSN3/Cu2O/DMF/MeOH,[8a]
TMSN3/Me3Al/toluene/reflux,[8b] NaN3/tungstates/DMF,[9]
[a] Department of Chemistry, University of North Florida,
1 UNF Drive, Jacksonville, Florida 32224, USA
Fax: +1-904-620-3535
A number of energetic tetrazolium salts with 3,5-dinitro-
1,2,4-triazolate and other counterions have been reported
in several recent papers by Shreeve et al., who used 5-ami-
E-mail: kenneth.laali@UNF.edu
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201100957.
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G. Aridoss, K. K. Laali
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notetrazole as a key building block.[2] The focus of the cur- ficiently, forming the corresponding 5-aryl-1H-tetrazoles
rent study was to exploit the widely applicable method for with isolated yields in the 68–96% range (Table 2, En-
the preparation of the 5-substituted 1H-tetrazoles reported tries 2–8). With phthalonitrile, the isolated monotetrazole
here in order to gain access to tetrazolium-based ILs that product reacted further under the same set of conditions to
might find applications as catalysts and solvents in organic give the corresponding bis-tetrazole (Table 2, Entries 9 and
synthesis.
10). Tetrazole derivatives of bicyclic and polycyclic aro-
matics were synthesized conveniently by this method
(Table 2, Entries 11–13). Representative heterocyclic aro-
matic tetrazoles were also prepared in respectable isolated
yields (Table 2, Entries 14–16). Benzylnitrile reacted ef-
ficiently, allowing the synthesis of the 5-benzylic derivative
(Table 2, Entry 17). In representative cases, aliphatic nitriles
also reacted, but with heptanenitrile the isolated yield was
lower (Table 2, Entries 18 and 19).[18] With p-aminobenzo-
nitrile only a trace of the tetrazole was obtained (Table 2,
Entry 20),[19] and with cyclohexanecarbonitrile and ada-
mantane-1-carbonitrile the reactions did not proceed
(Table 2, Entries 21 and 22). The reported yields for o-nitro-
benzonitrile[1c,9,10] and o-methoxybenzonitrile[8b] do not
indicate any noticeable drop in the levels of conversion due
to steric effects, but a low yield reported for o-bromobenzo-
nitrile[10] and the lack of reaction with cyclohexanecar-
bonitrile and adamantane-1-carbonitrile in this study do
suggest that increased steric crowding can have a notable
effect on the yields.
Results and Discussion
Synthesis of 5-Substituted 1H-Tetrazoles
Initially, a comparative study focusing on the synthesis of
5-phenyltetrazole was carried out with use of three different
heterogeneous catalysts – Cu–Sn alloy, Cu–Zn couple, and
Cu–Zn alloy nanopowder – and NaN3 in DMF at reflux
(Table 1). The results indicated that Cu–Zn alloy was supe-
rior, providing higher isolated yields in shorter times and
with smaller quantities of the catalysts. Recycling and reuse
of the catalyst was also tested in two subsequent cycles and
showed minimal decreases in the isolated yields (see
Table 1). Under these conditions, NaN3 was found to be
superior to TMSN3.
Table 1. Comparative study of catalysts for the synthesis of 5-phen-
yltetrazole.[a]
Entry
Catalyst
Azide Time
Yield
[%]
source
[h]
1
2
3
4
5
6
Cu–Sn alloy[b] (100 mg)
Cu–Zn couple[c] (100 mg)
Cu–Zn alloy[d] (100 mg)
Cu–Zn alloy[d] (50 mg)
Cu–Zn alloy[d] (38 mg)[e]
Cu–Zn alloy[d] (38 mg)
NaN3
NaN3
NaN3
NaN3
NaN3
TMSN3
28
20
10
10
10
24
52
78
89
Scheme 1. Synthesis of 5-substituted tetrazoles catalyzed by Cu–Zn
alloy nanopowder.
92
95 (92[f], 84[g])
53
[a] Benzonitrile (2 mmol) + azide source (2.8 mmol) + catalyst
(x mg) + DMF (6 mL) at 120 °C. [b] Bronze – spherical powder –
200 mesh (Product No. 520365, Aldrich). [c] Prepared by the re-
ported procedure.[15] [d] Nanopowder, Ͻ150 nm particle size, 56–
60% (Cu basis), 37–41% (Zn basis) (procured from Aldrich prod-
uct No. 593583). [e] Further decreases in catalyst amount lowered
the yields and increased the reaction times. [f, g] These yields corre-
spond to the second and third runs, respectively, with the recycled
catalyst.
Synthesis of 1,5- and 2,5-Substituted Tetrazoles
Treatment of 5-substituted 1H-tetrazoles, prepared in
situ as shown in Scheme 2, with benzyl bromide or n-butyl
bromide gave the corresponding 1,5- (isomers a) and 2,5-
disubstituted (isomers b) derivatives as mixtures in which
the b isomers were the major products. The highest percen-
tage of an a isomer was obtained in the case of furanyl-
On the basis of this survey study, the RCN/NaN3/Cu–Zn tetrazole (Table 3, Entry 5).
alloy nanopowder/DMF system was selected as the method
Dialkylated tetrazole derivatives were also synthesized by
of choice (Scheme 1) for examination of the scope of this treatment of the corresponding tetrazoles with Et3N/nBuBr
transformation (Table 2). Benzonitrile derivatives bearing a in acetonitrile as solvent (see Experimental Section and
host of activating and deactivating substituents reacted ef- Table 3). The resulting isomeric dialkylated mixtures were
Scheme 2. One-pot syntheses of isomeric 1,5- and 2,5-disubstituted tetrazoles.
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Highly Efficient Synthesis of 5-Substituted 1H-Tetrazoles Catalyzed by Cu–Zn
Table 2. Scope of [3+2] cycloaddition reactions between nitriles and NaN3 catalyzed by Cu–Zn alloy nanopowder.
[a] A trace of bis-tetrazole derivative was formed with a 1:1 molar ratio of nitrile to sodium azide. An increase in the molar ratio of azide
resulted in increased formation of the monotetrazole derivative with only 15% of the disubstitution product. NR – no reaction.
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Table 3. One-pot syntheses of 1,5- (a) and 2,5-substituted (b) tetrazoles catalyzed by Cu–Zn alloy nanopowder.
[a] Isomer ratio determined by GC–MS. [b] With NEt3, isomers were formed in 1:0.57 ratio (relative yield: 62:34). [c] With NEt3, isomers
were formed in 1:0.73 ratio (relative yield: 52:38).
conveniently separated by conventional chromatography. In cible with Et2O, whereas the triflates and ethyl sulfate salts
the 13C NMR spectra the tetrazole ring carbons are very are hydrophilic and immiscible with Et2O. These attributes
distinct, appearing at ca. 155 ppm in isomers a and at ca. make them promising as solvents/catalysts for organic syn-
167 ppm in isomers b.
With the 1,5- and 2,5-disubstituted derivatives at hand cedures, in line with those of imidazolium ILs.
we focused our attention on the synthesis of tetrazolium- The ethyl sulfate salts 32a/32aЈ (1:1) and the NTf2 salts
based ionic liquids for possible application as catalysts and 34a/34aЈ (1:1) were subjected to a detailed 2D NMR study
thesis, offering the possibility for simple workup pro-
solvents in organic synthesis.
(TOCSY, COSY, NOESY, HSQC, and HMBC – Fig-
ures S1–S7 in the Supporting Information) to allow specific
assignment of the positions of the ethyl groups and the pro-
ton signals in the 1:1 mixtures (Tables S1 and S2 in the Sup-
porting Information).
Synthesis of New Tetrazolium-Based Ionic Liquids
Four dialkyltetrazoles bearing aliphatic chains – 1,5-di-
butyl- (28a, Scheme 3), 1-butyl-5-hexyl- (29a), 2,5-dibutyl-
Formation of pairs of isomeric onium salts was further
(28b), and 2-butyl-5-hexyltetrazole (29b) – were selected as confirmed by 15N NMR, which showed two sets of four
building blocks for the synthesis of ionic liquids.
nitrogen resonances (Table 6). Unambiguous assignment of
Whereas alkylation of the 2,5-dialkyltetrazoles selectively the individual nitrogen resonances was achieved through
1
gave onium salts alkylated at N-4, with the 1,5-dialkyl de- the H/15N HMBC spectra (Figures S12/S13 and S25/S26
rivatives almost 1:1 mixtures of two tetrazolium salts were in the Supporting Information) recorded for compounds
formed by alkylation at N-3 and N-4 (Table 4). The triflate 28a/28b, 32a/32aЈ, and 32b (HMBC correlations are given
salts were prepared by treatment with EtOTf in DCM, in Tables S3–S5 in the Supporting Information).
whereas the ethyl sulfate salts were synthesized by alky-
In the 15N NMR spectrum of 32a/32aЈ (Figure S18/Table
lation with diethyl sulfate in toluene. Metathesis with S4 in the Supporting Information), one of the nitrogen sig-
LiNTf2 furnished the corresponding NTf2 salts. The triflate nals (N-1) is buried under the signal from CD3CN solvent.
and ethyl sulfate salts were room-temperature ionic liquids, This was confirmed by re-recording the spectrum in CDCl3
1
whereas the NTf2 salts were low-melting ILs (see Experi- (Figure S19 in the Supporting Information). In the H/15N
mental). As with most imidazolium and pyridinium ILs, the HMBC spectrum (Figure S25 in the Supporting Infor-
tetrazolium salts prepared in this study exhibit good solu- mation) the nitrogen resonance at –91.73 ppm exhibited a
bility in acetonitrile, acetone, and dichloromethane strong cross-peak with the ethyl protons, whereas no such
(Table 5). The NTf2 salts are hydrophobic and partially mis- correlation was detected with either of the n-butyl groups
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Highly Efficient Synthesis of 5-Substituted 1H-Tetrazoles Catalyzed by Cu–Zn
Table 4. Synthesis of tetrazolium-based ionic liquids.
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Scheme 3. Synthesis of isomeric 1,5- and 2,5-disubstituted tetrazole-based ionic liquids.
Table 5. Miscibilities of tetrazolium ILs in various solvents.[a]
Entry
Ionic liquid
Toluene
DCM
Hexane
Acetone
Acetonitrile
Water
Ether
1
2
3
4
5
6
30a/aЈ and 30b
31a/aЈ and 31b
32aaЈ and 32b
33a/aЈ and 33b
34a/aЈ and 34b
35a/aЈ and 35b
NM
NM
NM
NM
M
M
M
M
M
M
M
NM
NM
NM
NM
NM
NM
M
M
M
M
M
M
M
M
M
M
M
M
M
M
M
M
NM
NM
NM
NM
NM
NM
PM
PM
M
[a] M – miscible; NM – not miscible; PM – partially miscible.
(of the major isomer). On this basis, this signal was assigned
Electrospray mass spectra of the ILs in the positive ion
to N-3. In the other isomer, the signal at –135.02 ppm mode showed intense signals for intact cations and rela-
showed a strong cross-peak with the ethyl protons in ad- tively less intense cation/molecule cluster ions. In the nega-
dition to the n-butyl CH2 group (attached directly to the tive ion mode, apart from the anions, observation of anion/
ring carbon), so this nitrogen signal was assigned to N-4 molecule cluster ions was noteworthy.
(which bears the ethyl group). A clear trend of substituent
effects on the 15N NMR chemical shifts is observed in going
from the dialkyltetrazole precursors to the N-ethylated salts
Summary
(see Table 6). Except for N1, which is somewhat deshielded, The facile and quite general method for the synthesis of 5-
the Δδ15N values exhibit an upfield trend in going from substituted 1H-tetrazoles described above, together with the
dialkyltetrazoles to the tetrazolium ILs (the upfield shifts in relatively straightforward syntheses of 1,5- and 2,5-dialkyl
the 15N values are most pronounced for the nitrogen atoms derivatives, provided the starting points for the synthesis of
undergoing alkylation), whereas Δδ13C values for the ring new tetrazolium-based ionic liquids with OTf, EtSO4, and
1
carbon remain relatively unchanged. Similar anion de- NTf2 counterions. Natural-abundance 15N NMR and H/
shielding and cation shielding trends can be deduced from 15N 2D NMR correlations were successfully utilized to ana-
the 15N NMR spectra of systems reported by Shreeve et lyze the resulting tetrazolium ILs and for specific assign-
al.[2f,2g,2h]
ment of the nitrogen chemical shifts.
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Highly Efficient Synthesis of 5-Substituted 1H-Tetrazoles Catalyzed by Cu–Zn
Table 6. 15N (and 13C) NMR chemical shifts for the tetrazole moiety in N-alkyltetrazoles and their ionic liquids.[a,b]
[a] Δδ15N NMR values: cation minus neutral. [b] To the best of our knowledge the 15N NMR chemical shift of NTf2– has not been reported.
In the 15N NMR spectrum of 34a/34aЈ in CD3CN (Figure S21 in the Supporting Information) and in CDCl3 (Figure S22 in the Supporting
Information) no signal attributable to the anion was detectable. For the tetrazolium salt 34b (Figure S23 in the Supporting Information)
the 15N spectrum recorded in CD3CN did not exhibit a signal for the anion, whereas in CDCl3, (Figure S24 in the Supporting Information)
a small peak at –243.07 was observed. This chemical shift is close to the reported value of –237.1 ppm for (C2F5SO2)2N–.[27]
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H) ppm. 13C NMR (125 MHz, [D6]DMSO): δ = 55.46 (OCH3),
114.87, 116.29, 128.65, 154.72 (br.), 161.48 ppm.
We plan to incorporate these ILs into our synthetic/
mechanistic projects that continue to focus on electrophilic
and onium ion chemistry in ILs.[4,20]
5-(4-Fluorophenyl)tetrazole (4): Yield 68% (0.22 g), off-white solid,
1
m.p. 191–192 °C. H NMR (500 MHz, [D6]DMSO): δ = 7.46 (t, J
= 9.0 Hz, 2 H), 8.08–8.10 (m, 2 H) ppm. 13C NMR (125 MHz, [D6]-
DMSO): δ = 116.61 (d, J = 22.25 Hz), 128.66 (d, J = 4.25 Hz),
129.48 (d, J = 8.75 Hz), 154.79 (br.), 163.65 (d, J = 247.63 Hz, C–
F) ppm. 19F NMR (470.2 MHz, CDCl3): δ = –109.62 (m) ppm. IR
Experimental Section
(CH Cl ): ν = 2924, 1663, 1611, 1499, 1242, 1161 cm–1. MS (EI):
˜
2
2
General: The reagents employed were high-purity commercial sam-
ples and were used without further purification. Column
chromatography was performed on silica gel (32–63 particle size).
Melting points were recorded with a MEL-TEMP apparatus and
are uncorrected. Both 1D and 2D NMR spectra were recorded in
CDCl3, CD3CN, or [D6]DMSO with a Varian INOVA 500 MHz
instrument. Chemical shifts were referenced to internal solvent sig-
m/z (%) = 164 [M]+, 136 (100) [M – N2]+, 121 [M – HN3]+, 109,
95 [M – tetrazole]+, 75, 57.
5-[4-(Trifluoromethyl)phenyl]tetrazole (5):[10] Yield 93% (0.39 g),
1
white solid, m.p. 220–221 °C. H NMR (500 MHz, [D6]DMSO): δ
= 7.98 (d, J = 8.0 Hz, 2 H), 8.25 (d, J = 8.0 Hz, 2 H) ppm. 13C
NMR (125 MHz, [D6]DMSO): δ = 123.87 (q, J = 271 Hz, CF3),
126.43 (q, J = 3.75 Hz), 127.79, 128.46, 130.99 (q, J = 31.94 Hz),
155.30 (br.) ppm. 19F NMR (470.2 MHz, CDCl3): δ = –61.58
(s) ppm.
1
1
nals: H at δ = 7.26 ppm/13C at δ = 77.16 ppm for CDCl3, H at δ
= 1.94 ppm/13C at 1.32 and 118.26 ppm for CD3CN, and 1H at
2.50 ppm/13C at δ = 39.52 ppm for [D6]DMSO. 19F spectra were
referenced relative to external CFCl3. The 15N NMR spectra were
recorded at 50.66 MHz with CD3CN and CDCl3 as solvents.
Chemical shift values are referenced to external nitromethane
(neat). IR spectra (solution) were obtained with a SHIMADZU
FT-IR spectrophotometer. The IR and mass data for the new com-
pounds are reported. GC–MS analyses were performed with a
HP 5890 series II GC coupled to a HP 5972 series mass selective
detector instrument. Electrospray mass spectra were recorded with
a Bruker-Esquire system in both positive and negative ion modes.
The designations C+ (cation) and A– (anion) are used in reporting
of electrospray-MS data.
4-(Tetrazol-5-yl)benzaldehyde (6):[21] Yield 91% (0.31 g), white so-
lid, m.p. 184–185 °C. 1H NMR (500 MHz, [D6]DMSO): δ = 8.11
(d, J = 8.0 Hz, 2 H), 8.24 (d, J = 8.0 Hz, 2 H), 10.08 (s, 1 H,
–CHO) ppm. 13C NMR (125 MHz, [D6]DMSO): δ = 127.60,
129.53, 130.37, 137.60, 155.40 (br.), 192.69 (–CHO) ppm.
5-(4-Acetylphenyl)tetrazole (7):[6] Yield 77% (0.29 g), white solid,
1
m.p. 171–173 °C. H NMR (500 MHz, [D6]DMSO): δ = 2.64 (s, 3
H, –COCH3), 8.14–8.19 (m, 4 H) ppm. 13C NMR (125 MHz, [D6]-
DMSO): δ = 26.90 (COCH3), 127.20, 129.18, 130.15, 138.44,
155.31 (br.), 197.45 (COCH3) ppm.
5-(4-Nitrophenyl)tetrazole (8):[6] Yield 96% (0.37 g), yellow solid,
m.p. 217 °C. 1H NMR (500 MHz, [D6]DMSO): δ = 8.28 (d, J =
8.8 Hz, 2 H), 8.42 (d, J = 8.8 Hz, 2 H) ppm. 13C NMR (125 MHz,
[D6]DMSO): δ = 124.57, 128.17, 130.63, 148.71, 155.41 (br., C-
N4) ppm.
General Procedure for the Synthesis of 5-Substituted Tetrazoles
(Compounds 1–22): Cu–Zn alloy nanopowder (38 mg) was added
to a mixture of the nitrile (2 mmol) and sodium azide (2.8 mmol)
in DMF (6 mL) and the mixture was stirred under ambient condi-
tions for the specified time and temperature (Table 2, monitoring
by TLC). After completion, the resulting mixture was allowed to
cool to room temperature and the catalyst was separated by centri-
fugation and washed with ethyl acetate (three times). The resulting
centrifugate was treated with HCl (5 n, 10 mL) and ethyl acetate
(used to wash the catalyst) with stirring. The organic layer was
separated and the aqueous solution left behind was extracted fur-
ther with ethyl acetate. The combined organic extracts were washed
with water and concentrated to furnish the desired tetrazole. Most
of the compounds were obtained in pure form after simple tritura-
tion with hexane, whereas a few others were purified by column
chromatography (32–63 particle size; hexane/ethyl acetate 1:1). In
a representative case (Table 1), the recovered catalyst was reused in
two successive runs without any significant decrease in the product
yields.
5-(2-Benzonitrile)tetrazole (9):[22] Yield 75% (0.26 g), white solid,
1
m.p. 220–221 °C. H NMR (500 MHz, [D6]DMSO): δ = 7.77 (dt,
J = 1, 7.8 Hz, 1 H), 7.92 (dt, J = 1.2, 7.8 Hz, 1 H), 8.07 (t, J =
8.8 Hz, 2 H) ppm. 13C NMR (125 MHz, [D6]DMSO): δ = 110.69
(C–CN), 117.72 (C–CN), 128.05, 130.18, 131.86, 134.29, 135.43,
156.00 (br., C-N4) ppm.
1,2-Bis(5-tetrazolyl)benzene (10):[5,22] Yield 88% (0.38 g), yellow so-
1
lid, m.p. 226–229 °C. H NMR (500 MHz, [D6]DMSO): δ = 7.80–
7.83 (m, 2 H), 7.90–7.93 (m, 2 H) ppm. 13C NMR (125 MHz, [D6]-
DMSO): δ = 124.55, 130.77, 131.34, 154.87 (br., C-N4) ppm.
5-[2-(4Ј-Methyl)biphenyl]tetrazole (11):[6] Yield 82% (0.39 g), pale
yellow solid, m.p. 151 °C. 1H NMR (500 MHz, [D6]DMSO): δ =
2.30 (s, 3 H, –CH3), 6.97 (d, J = 7.9 Hz, 2 H), 7.13 (d, J = 7.9 Hz,
2 H), 7.55 (t, J = 6.8 Hz, 2 H), 7.63–7.71 (m, 2 H) ppm. 13C NMR
(125 MHz, [D6]DMSO): δ = 20.89 (CH3), 123.33, 127.77, 128.69,
129.12, 130.86, 131.10, 131.29, 136.52, 137.10, 141.67, 155.12 (br.,
C-N4) ppm.
5-(Phenanthren-9-yl)tetrazole (12):[23] Yield 78% (0.38 g), white so-
lid, m.p. 239–241 °C. 1H NMR (500 MHz, [D6]DMSO): δ = 7.76
(t, J = 7.5 Hz, 2 H), 7.84 (q, J = 8.3 Hz, 2 H), 8.13 (d, J = 8.0 Hz,
1 H), 8.37 (s, 1 H), 8.49 (d, J = 8.00 Hz, 1 H), 8.95 (d, J = 8.18 Hz,
1 H), 9.0 (d, J = 8.0 Hz, 1 H) ppm. 13C NMR (125 MHz, [D6]-
DMSO): δ = 120.60, 123.14, 123.58, 125.95, 127.70, 127.73, 127.75,
128.31, 128.88, 129.41, 130.05, 130.20, 130.68, 155.13 (br., C-N4,
two coinciding carbon resonances) ppm.
5-Phenyltetrazole (1):[6] Yield 95% (0.27 g), white solid, m.p. 215–
216 °C. 1H NMR (500 MHz, [D6]DMSO): δ = 7.57–7.63 (m, 3 H),
8.01–8.03 (m, 2 H) ppm. 13C NMR (125 MHz, [D6]DMSO): δ =
124.56, 127.41, 129.88, 131.71, 155.76 (br.) ppm.
5-(3-Methoxyphenyl)tetrazole (2):[6] Yield 89% (0.31 g), off-white
1
solid, m.p. 158 °C. H NMR (500 MHz, [D6]DMSO): δ = 3.83 (s,
3 H, –OCH3), 7.19 (dd, J = 2.5 8.5 Hz, 1 H), 7.54 (t, J = 8.1 Hz,
1 H), 7.55–7.60 (m, 2 H) ppm. 13C NMR (125 MHz, [D6]DMSO):
δ = 55.81 (OCH3), 111.82, 116.81, 119.43, 125.01, 131.12, 155.43
(br.), 159.70 ppm.
5-(4-Methoxyphenyl)tetrazole (3):[5] Yield 90% (0.32 g), white solid,
1
m.p. 230–232 °C. H NMR (500 MHz, [D6]DMSO): δ = 3.82 (s, 3
5-(9-Anthryl)tetrazole (13):[23] Yield 14% (0.07 g), yellow solid, m.p.
270–271 °C. 1H NMR (500 MHz, [D6]DMSO): δ = 7.44 (d, J =
H, –OCH3); 7.14 (d, J = 9.0 Hz, 2 H), 7.96 (d, J = 9.0 Hz, 2
6350
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 6343–6355

Highly Efficient Synthesis of 5-Substituted 1H-Tetrazoles Catalyzed by Cu–Zn
8.5 Hz, 2 H), 7.54–7.61 (m, 4 H), 8.22 (d, J = 8.5 Hz, 2 H), 8.91
(s, 1 H) ppm. 13C NMR (125 MHz, [D6]DMSO): δ = 118.08,
124.41, 125.87, 127.72, 128.77, 129.66, 130.39, 130.50, 152.54 (br.,
C-N4) ppm.
bonate, and brine and dried with MgSO4. The solvent was removed
under reduced pressure to furnish the corresponding N-alkylated
tetrazole as a mixture of two isomers. The individual isomers were
conveniently separated by chromatography with hexane/ethyl acet-
ate (1:0.5).
5-(2-Furyl)tetrazole (14):[6] Yield 92% (0.25 g), off-white solid, m.p.
1
206–208 °C. H NMR (500 MHz, [D6]DMSO): δ = 6.76 (dd, J =
2) Starting from a Tetrazole: Compounds 28a/28b and 29a/29b can
also be prepared by starting from the corresponding tetrazoles with
use of NEt3 as catalyst. Triethylamine (1 mmol) was added to the
appropriate tetrazole 18 or 19 (2 mmol) in MeCN, and the reaction
mixture was stirred initially for about half an hour. nBuBr
[(2.1 mmol)] was then added dropwise with stirring at room temp.
followed by reflux for 3 to 4 h. Upon completion of reaction, the
resulting mixture was allowed to cool to room temp., poured into
cold water, and extracted three times with ethyl acetate. The com-
bined organic phase was washed with water and brine and dried
with Na2SO4. Upon removal of solvent under reduced pressure the
desired N-butyltetrazoles were isolated as isomeric mixtures, which
were then separated as described above.
2.0, 3.0 Hz, 1 H), 7.25 (dd, J = 0.5, 3.5 Hz, 1 H), 8.02 (dd, J = 0.5,
1.5 Hz, 1 H) ppm. 13C NMR (125 MHz, [D6]DMSO): δ = 112.91,
113.43, 140.34, 146.53, 148.73 (br., C-N4) ppm.
3-(Tetrazol-5-yl)pyridine (15):[6] Yield 72% (0.21 g), white solid,
1
m.p. 241–242 °C. H NMR (500 MHz, [D6]DMSO): δ = 7.64 (dd,
J = 5.0, 8.0 Hz, 1 H), 8.39 (dt, J = 1.5, 8.0 Hz, 1 H), 8.76 (br. s, 1
H), 9.22 (br. s, 1 H) ppm. 13C NMR (500 MHz, [D6]DMSO): δ =
121.45, 124.38, 134.47, 147.60, 151.63, 154.46 (br., C-N4) ppm.
2-(2H-tetrazol-5-yl)pyrazine (16):[5] Yield 81% (0.24 g), off-white
solid, m.p. 187–188 °C. 1H NMR (500 MHz, [D6]DMSO): δ = 8.88
(s, 2 H), 9.40 (s, 1 H) ppm. 13C NMR (500 MHz, [D6]DMSO): δ =
140.00, 143.39, 144.89, 146.83, 153.55 (br.) ppm.
1-Benzyl-5-phenyltetrazole (23a):[24] Yield 13% (0.06 g), white
microcrystals, m.p. 87–88 °C. 1H NMR (500 MHz, CDCl3): δ =
5.61 (s, 2 H, –CH2), 7.14–7.16 (m, 2 H), 7.32–7.36 (m, 3 H), 7.48–
7.51 (m, 2 H), 7.54–7.59 (m, 3 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 51.46 (CH2), 123.88, 127.27, 128.87, 128.97, 129.29,
5-Benzyltetrazole (17):[6] Yield 80% (0.26 g), white solid, m.p. 124–
125 °C. 1H NMR (500 MHz, [D6]DMSO): δ = 4.29 (s, 2 H,
–CH2Ph), 7.24–7.27 (m, 3 H), 7.32–7.35 (m, 2 H) ppm. 13C NMR
(500 MHz, [D6]DMSO): δ = 28.91 (–CH2Ph), 127.04, 128.67,
128.74, 136.00, 155.17 (br., C-N4) ppm.
129.30, 131.45, 134.03, 154.81 ppm. IR (CH Cl ): ν = 3063, 3032,
˜
2
2
2918, 2849, 1472, 1454, 1402, 1107 cm–1. MS (EI): m/z (%) = 236
5-Butyltetrazole (18):[6] Yield 84% (0.21 g), white crystalline solid,
m.p. 42 °C. 1H NMR (500 MHz, [D6]DMSO): δ = 0.88 (t, J =
7.5 Hz, 3 H, –CH2CH2CH2CH3), 1.3 (sextet, J = 7.3 Hz, 2 H,
[M]+, 179, 91 (100) [C7H7]+, 77, 65, 51.
2-Benzyl-5-phenyltetrazole (23b):[25] The literature did not provide
NMR spectroscopic data. Yield 70% (0.33 g), white microcrystals,
m.p. 61–62 °C. 1H NMR (500 MHz, CDCl3): δ = 5.81 (s, 2 H,
–CH2), 7.34–7.44 (m, 5 H), 7.45–7.50 (m, 3 H), 8.13–8.15 (m, 2
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 56.95 (CH2), 127.01,
127.50, 128.51, 128.98, 129.08, 129.15, 130.44, 133.50, 165.59 ppm.
–CH2CH2CH2CH3), 1.66 (quint.,
–CH2CH2CH2CH3), 2.86 (t,
CH2CH3) ppm. 13C NMR (500 MHz, [D6]DMSO): δ = 13.48
(–CH2CH2CH2CH3), 21.51 (–CH2CH2CH2CH3), 22.36
J
=
7.5 Hz,
2
H,
J
= 7.5 Hz, 2 H, –CH2CH2-
(–CH2CH2CH2CH3), 29.09 (–CH2CH2CH2CH3), 155.73 (C-
N4) ppm.
IR (CH Cl ): ν = 3067, 3034, 1530, 1497, 1466, 1449, 1044,
˜
2
2
5-Hexyltetrazole (19): Yield 62% (0.19 g), colorless oil, 1H NMR
1028 cm–1. MS (EI): m/z (%) = 236 [M]+, 207, 179 (100), 165, 91
[C7H7]+, 77, 63, 51.
(500 MHz, CDCl3):
δ
=
0.84 (t,
J
=
7.0 Hz,
3
H,
–CH2CH2CH2CH2CH2CH3), 1.24–1.3 (m, 4 H, –CH2CH2CH2-
CH2CH2CH3), 1.36–1.40 (m, 2 H, –CH2CH2CH2CH2CH2CH3),
1.86 (quint., J = 7.5 Hz, 2 H, –CH2CH2CH2CH2CH2CH3), 3.1 (t,
J = 7.8 Hz, 2 H, –CH2CH2CH2CH2CH2CH3) ppm. 13C NMR
(500 MHz, CDCl3): δ = 14.06 (–CH2CH2CH2CH2CH2CH3), 22.51
(–CH2CH2CH2CH2CH2CH3), 23.60 (–CH2CH2CH2CH2CH2-
CH3), 27.76 (–CH2CH2CH2CH2CH2CH3), 28.79 (–CH2CH2-
CH2CH2CH2CH3), 31.34 (–CH2CH2CH2CH2CH2CH3), 157.08
1-Benzyl-5-(4-methoxyphenyl)tetrazole (24a):[24] Yield 14% (0.07 g),
white solid, m.p. 105–106 °C. 1H NMR (500 MHz, CDCl3): δ =
3.86 (s, 3 H, –OCH3); 5.61 (s, 2 H, –CH2), 6.99 (d, J = 8.8 Hz, 2
H), 7.15–7.17 (m, 2 H), 7.34–7.38 (m, 3 H), 7.54 (d, J = 8.8 Hz, 2
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 51.39 (CH2), 55.60
(OCH3), 114.79, 115.86, 127.17, 128.84, 129.33, 130.50, 134.21,
154.66, 162.02 ppm. IR (CH Cl ): ν = 2922, 2841, 1611, 1478,
˜
2
2
1447, 1258, 1179, 1020 cm–1. MS (EI): m/z (%) = 266 [M]+, 224
(C-N ) ppm. IR (CH Cl ): ν = 2957, 2928, 2859, 1668, 1559, 1460,
˜
4
2
2
[M – N3]+, 209, 195, 119 [M – BnN2]+, 91 (100) [C7H7]+, 65.
1254, 1057 cm–1. MS (EI): m/z (%) = 111 [M – propyl]+, 97 [M –
butyl]+, 84 [M – tetrazole]+, 69 [M – hexyl]+, 55 (100), 43, 39.
2-Benzyl-5-(4-methoxyphenyl)tetrazole (24b): Yield 65% (0.35 g),
spongy, white solid, m.p. 117–118 °C. 1H NMR (500 MHz,
CDCl3): δ = 3.86 (s, 3 H, –OCH3); 5.78 (s, 2 H, –CH2), 6.98 (d, J
= 8.8 Hz, 2 H), 7.34–7.42 (m, 5 H), 8.07 (d, J = 8.8 Hz, 2 H) ppm.
13C NMR (125 MHz, CDCl3): δ = 55.50 (CH2), 56.84 (OCH3),
114.37, 120.11, 128.49, 128.52, 129.03, 129.13, 133.61, 161.37,
General Procedure for the Synthesis of 1,5- and 2,5-Disubstituted
Tetrazoles (23a/23b to 29a/29b)
1) One-Pot Reaction Starting from a Nitrile: Cu–Zn alloy nano-
powder (38 mg) was added to a mixture of a nitrile (2 mmol) and
sodium azide (2.8 mmol) in DMF (6 mL) and the mixture was
stirred at 90–120 °C until the TLC confirmed complete conversion
of the nitrile. At that point the reaction mixture was allowed to
cool to room temperature and benzyl bromide (1.2 equiv. relative to
tetrazole product) or butyl bromide (1.2 equiv. relative to tetrazole
product) was added. The contents were further stirred at 80 °C un-
til completion (monitoring by TLC; see Table 3). After completion,
the catalyst was separated off by centrifugation and washed with
ethyl acetate (3 times). Water was added to the centrifugate and
organics were extracted into ethyl acetate (three times). The com-
165.48 ppm. IR (CH Cl ): ν = 2924, 1614, 1466, 1254, 1028,
˜
2
2
833 cm–1. MS (EI): m/z (%) = 207, 180, 165, 103, 91 (100)
[C7H7]+, 77, 63, 50.
1-Benzyl-5-[4-(trifluoromethyl)phenyl]tetrazole (25a): Yield 5%
(0.03 g), white solid, m.p. 103–104 °C. 1H NMR (500 MHz,
CDCl3): δ = 5.64 (s, 2 H, CH2), 7.14–7.16 (m, 2 H), 7.36–7.38 (m,
3 H), 7.72 (d, J = 8.3 Hz, 2 H), 7.77 (d, J = 8.3 Hz, 2 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 51.75 (CH2), 123.56 (q, J =
271.7 Hz, –CF3), 126.34 (q, J = 3.6 Hz), 127.16, 129.18, 129.50,
bined organic extracts was then washed with water, hydrogencar- 129.52, 133.45 (q, J = 32.4 Hz), 133.67, 153.72 (two coinciding car-
Eur. J. Org. Chem. 2011, 6343–6355
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6351

G. Aridoss, K. K. Laali
FULL PAPER
bon resonances) ppm. 19F NMR (470.2 MHz, CDCl3): δ = –63.17
2,5-Dibutyltetrazole (28b): Yield 51% (0.19 g), with NEt3 as cata-
(s) ppm. IR (CH Cl ): ν = 2922, 2851, 1449, 1425, 1323, 1171, lyst: Yield 62% (0.23 g), colorless liquid, 1H NMR (500 MHz,
˜
2
2
1123, 1067 cm–1. MS (EI): m/z (%) = 304 [M]+, 275, 248, 179, 91
CDCl3): δ = 0.90* (t, J = 7.0 Hz, 3 H), 0.91* (t, J = 7.0 Hz, 3 H),
1.28–1.40 (m, 4 H), 1.73** (quint., J = 8.2 Hz, 2 H), 1.94** (quint.,
J = 7.5 Hz, 2 H), 2.84 (t, J = 7.8 Hz, 2 H), 4.52 (t, J = 7.3 Hz, 2
H) ppm. 13C NMR (500 MHz, CDCl3): δ = 13.44, 13.78, 19.67,
(100) [C7H7]+, 77, 65, 51.
2-Benzyl-5-[4-(trifluoromethyl)phenyl]tetrazole (25b): Yield 77%
1
(0.47 g), white solid, m.p. 73–74 °C. H NMR (500 MHz, CDCl3):
22.30, 25.21, 30.26, 31.35, 52.66, 166.94 ppm. IR (CH Cl ): ν =
˜
2
2
δ = 5.83 (s, 2 H, –CH2), 7.36–7.45 (m, 5 H), 7.73 (d, J = 8.3 Hz, 2
H), 8.26 (d, J = 8.1 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3):
δ = 57.16 (CH2), 124.01 (q, J = 270.3 Hz, –CF3), 125.99 (q, J =
3.7 Hz), 127.31, 128.60, 129.23, 129.25, 130.87, 132.21 (q, J =
32.4 Hz), 133.22, 164.41 ppm. 19F NMR (470.2 MHz, CDCl3): δ =
2961, 2934, 2874, 1495, 1466, 1402, 1358, 1026 cm–1. MS (EI): m/z
(%) = 183 [M + 1]+, 154 [M – N2]+, 111 (100) [M – C5H12]+, 84,
57, 41. * Overlapping signals; ** partially resolved.
1-Butyl-5-hexyltetrazole (29a): Yield 11% (0.05 g), with NEt3 as
1
catalyst: Yield 38% (0.13 g), colorless liquid. H NMR (500 MHz,
–62.90 (s) ppm. IR (CH Cl ): ν = 2924, 1545, 1427, 1323, 1167,
˜
2
2
1125, 1067, 853 cm–1. MS (EI): m/z (%) = 275, 248, 179, 91 (100)
CDCl3): δ = 0.82* (t, J = 7.0 Hz, 3 H), 0.90 (t, J = 7.5 Hz, 3 H),
1.23–1.37 (m, 8 H), 1.75 (quint., J = 7.7 Hz, 2 H), 1.82 (quint., J
= 7.5 Hz, 2 H), 2.76 (t, J = 8 Hz, 2 H), 4.19 (t, J = 7.5 Hz, 2
H) ppm. 13C NMR (500 MHz, CDCl3): δ = 13.43, 13.97 19.66,
22.42, 23.17, 27.15, 28.80, 31.31, 31.64, 46.71, 154.79 ppm. IR
[C7H7]+, 77, 65, 51.
4-(1-Benzyltetrazol-5-yl)benzaldehyde (26a): Yield 10% (0.05 g),
white solid, m.p. 117–118 °C. 1H NMR (500 MHz, CDCl3): δ =
5.66 (s, 2 H, –CH2), 7.14–7.16 (m, 2 H), 7.35–7.37 (m, 3 H), 7.78
(d, J = 8.3 Hz, 2 H), 8.01 (d, J = 8.6 Hz, 2 H), 10.10 (s, 1 H,
–CHO) ppm. 13C NMR (125 MHz, CDCl3): δ = 51.85 (CH2),
127.22, 129.19, 129.50, 129.75, 130.29, 133.64, 138.13, 154.55 (br.),
191.20 (two coinciding carbon resonances, –CHO) ppm. IR
(CH Cl ): ν = 2959, 2932, 2872, 2860, 1518, 1462, 1464, 1092 cm–1.
˜
2
2
MS (EI): m/z (%) = 211 [M + 1]+, 153 [M – butyl]+, 112, 85, 55,
41 (100). * Partially resolved.
2-Butyl-5-hexyltetrazole (29b): Yield 33% (0.14 g) [with NEt3 as
catalyst: Yield 52% (0.22 g)], colorless liquid, 1H NMR (500 MHz,
CDCl3): δ = 0.83 (t, J = 7.3 Hz, 3 H), 0.91 (t, J = 7.3 Hz, 3 H),
1.24–1.35 (m, 8 H), 1.73 (quint., J = 7.5 Hz, 2 H), 1.90–1.96 (m, 2
H), 2.83 (t, J = 7.8 Hz, 2 H), 4.52 (t, J = 7.0 Hz, 2 H) ppm. 13C
NMR (500 MHz, CDCl3): δ = 13.43, 14.08, 19.66, 22.56, 25.51,
(CH Cl ): ν = 2922, 2851, 1703 (–C=O), 1614, 1449, 1206 cm–1.
˜
2
2
MS (EI): m/z (%) = 264 [M]+, 235 [M – CHO]+, 208, 179, 130, 91
(100) [C7H7]+, 77, 65, 51.
4-(2-Benzyltetrazol-5-yl)benzaldehyde (26b): Yield 64% (0.34 g),
1
white solid, m.p. 239–241 °C (dec.). H NMR (500 MHz, CDCl3):
28.14, 28.86, 31.35, 31.49, 52.64, 166.88 ppm. IR (CH Cl ): ν =
˜
2
2
δ = 5.83 (s, 2 H, CH2), 7.35–7.45 (m, 5 H), 7.99 (d, J = 8.5 Hz, 2
H), 8.32 (d, J = 8.5 Hz, 2 H), 10.07 (s, 1 H, –CHO) ppm. 13C
NMR (125 MHz, CDCl3): δ = 57.20 (CH2), 127.55, 128.61, 129.23,
129.26, 130.33, 132.92, 133.18, 137.53, 164.52, 191.78
2959, 2930, 2872, 2860, 1495, 1466, 1358, 1026 cm–1. MS (EI): m/z
(%) = 211 [M + 1]+, 167 [M – propyl]+, 153 [M – butyl]+, 139 [M –
pentyl]+, 112, 97, 69, 55, 41 (100).
General Procedure for the Synthesis of Tetrazolium Triflates
(Table 4): Ethyl triflate (1.1 mmol) was slowly added under nitrogen
to the appropriate 1,5- (28a, 29a) and 2,5-disubstituted tetrazole
(28b, 29b) (1 mmol) in dry DCM with stirring at ambient tempera-
ture. Stirring was continued for about 9 h (a purple color developed
after an hour and the color became more intense over time). Upon
completion, the excess solvent was removed under reduced pres-
sure, leaving behind the purple colored triflate salt as a resinous
liquid. This was washed with toluene and dried under reduced pres-
sure and in vacuo at 60 °C to furnish 30a/30b and 31a/31b salts as
pale brown liquids (room-temperature ILs).
(–CHO) ppm. IR (CH Cl ): ν = 3032, 2922, 2832, 1699 (–C=O),
˜
2
2
1613, 1535, 1202, 835 cm–1. MS (EI): m/z (%) = 235 [M – CHO]+,
208, 178, 104, 91 (100) [C7H7]+, 77, 63, 50.
1-Benzyl-5-(2-furyl)tetrazole (27a): Yield 30% (0.14 g), white solid,
1
m.p. 86 °C. H NMR (500 MHz, CDCl3): δ = 5.87 (s, 2 H, –CH2),
6.62 (dd, J = 1.80, 3.5 Hz, 1 H), 7.23 (dd, J = 0.7, 3.7 Hz, 1 H),
7.26–7.30 (m, 2 H), 7.31–7.35 (m, 3 H), 7.68 (dd, J = 0.7, 1.9 Hz,
1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 52.09 (CH2), 112.58,
115.16, 127.75, 128.83, 129.13, 134.02, 139.63, 145.52, 146.47 ppm.
IR (CH Cl ): ν = 3134, 1620, 1518, 1456, 1445, 1223, 1163,
˜
2
2
1009 cm–1. MS (EI): m/z (%) = 226 [M]+, 169, 141, 91 (100)
1,5-Dibutyl-3-ethyltetrazolium Triflate (30a) and 1,5-Dibutyl-4-eth-
yltetrazolium Triflate (30aЈ): Isomeric mixture (1:1). Yield 96%
(0.35 g), pale brown liquid, 1H NMR (500 MHz, CD3CN): δ = 0.97
(t, J = 7.3 Hz, 6 H), 0.98 (t, J = 7.5 Hz, 6 H), 1.40–1.55 (m, 8 H),
1.61 (t, J = 7.3 Hz, 3 H), 1.65 (t, J = 7.3 Hz, 3 H), 1.63–1.70 (m,
2 H), 1.77–1.83 (m, 2 H), 1.91–2.00 (m, 4 H), 3.04 (t, J = 7.7 Hz,
2 H), 3.17 (t, J = 8.2 Hz, 2 H), 4.48 (t, J = 7.3 Hz, 2 H), 4.49 (t, J
= 7.5 Hz, 2 H), 4.54 (q, J = 7.3 Hz, 2 H), 4.82 (q, J = 7.3 Hz, 2
H) ppm. 13C NMR (500 MHz, CD3CN): δ = 13.49, 13.63, 13.66,
13.68, 13.78, 13.99, 20.07, 20.14, 22.36, 22.54, 23.10, 23.76, 28.57,
28.81, 30.87, 31.11, 47.04, 51.06, 51.24, 53.92, 121.89 (q, J =
318.4 Hz, -CF3), 154.40, 162.60 ppm. 19F NMR (470.2 MHz,
[C7H7]+, 77, 65, 53.
2-Benzyl-5-(2-furyl)tetrazole (27b):[26] The literature ref. did not
1
provide characterization data. Yield 48% (0.22 g), pale red oil. H
NMR (500 MHz, CDCl3): δ = 5.79 (s, 2 H, –CH2), 6.54 (dd, J =
1.8, 3.5 Hz, 1 H), 7.11 (dd, J = 0.9, 3.55 Hz, 1 H), 7.34–7.42 (m, 5
H), 7.57 (dd, J = 0.8, 1.8 Hz, 1 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 57.02 (CH2), 111.53, 111.81, 128.56, 129.15, 133.16,
142.94, 144.36, 158.69 (two coinciding carbon resonances) ppm. IR
(CH Cl ): ν = 3131, 1630, 1514, 1499, 1456, 1431, 1227, 1179,
˜
2
2
1003 cm–1. MS (EI): m/z (%) = 226 [M]+, 170, 141, 115, 91 (100)
[C7H7]+, 65, 53, 39.
CD CN): δ = –79.37 (s) ppm. IR (CH Cl ): ν = 3422, 2967, 2878,
˜
3
2
2
1,5-Dibutyltetrazole (28a): Yield 11% (0.04 g), with NEt3 as cata-
lyst: Yield 34% (0.12 g), colorless liquid, 1H NMR (500 MHz,
CDCl3): δ = 0.92 (t, J = 7.3 Hz, 3 H), 0.93 (t, J = 7.3 Hz, 3 H),
1.30–1.44 (m, 4 H), 1.74–1.88 (m, 4 H), 2.79 (t, J = 7.8 Hz, 2 H),
4.21 (t, J = 7.0 Hz, 2 H) ppm. 13C NMR (500 MHz, CDCl3): δ =
13.50, 13.68, 19.72, 22.32, 22.93, 29.26, 31.70, 46.78, 154.86 ppm.
1466, 1262, 1225, 1161, 1030 cm–1. MS (ESI+): m/z (%) = 571 [CA/
C]+, 211 (100) [C]+, 155 [M – butyl]+, 84. MS (ESI–): m/z (%) =
509 [CA/A]–, 149 (100) [A]–.
2,5-Dibutyl-4-ethyltetrazolium Triflate (30b): Yield 95% (0.34 g),
1
pale brown liquid, H NMR (500 MHz, CD3CN): δ = 0.97 (t, J =
IR (CH Cl ): ν = 2961, 2934, 2874, 1518, 1462, 1424, 1381, 1238,
7.3 Hz, 3 H), 0.98 (t, J = 7.4 Hz, 3 H), 1.38–1.51 (m, 4 H), 1.59 (t,
J = 7.2 Hz, 3 H), 1.78–1.84 (m, 2 H), 2.01–2.07 (m, 2 H), 3.03 (t,
J = 7.7 Hz, 2 H), 4.54 (q, J = 7.3 Hz, 2 H), 4.78 (q, J = 7.2 Hz, 2
˜
2
2
1086 cm–1. MS (EI): m/z (%) = 183 [M + 1]+, 153 [M – ethyl]+, 140
[M – N3]+, 125 [M – butyl]+, 112, 84, 55, 41 (100).
6352
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 6343–6355

Highly Efficient Synthesis of 5-Substituted 1H-Tetrazoles Catalyzed by Cu–Zn
H) ppm. 13C NMR (500 MHz, CD3CN): δ = 13.52, 13.67, 13.77,
19.91, 22.56, 23.77, 28.46, 30.85, 47.26, 57.94, 121.43 (q, J =
(t, J = 7.5 Hz, 3 H), 1.0 (t, J = 3.5, J = 7.6 Hz, 3 H), 1.24 (t, J =
7.0 Hz, 3 H), 1.42–1.55 (m, 4 H), 1.61 (t, J = 7.3 Hz, 3 H), 1.80–
317.9 Hz, –CF3), 162.54 ppm. 19F NMR (470.2 MHz, CD3CN): δ 1.86 (m, 2 H), 2.03–2.09 (m, 2 H), 3.07 (t, J = 7.7 Hz, 2 H), 3.97
= –79.43 (s) ppm. IR (CH Cl ): ν = 3414, 2967, 2880, 1535, 1470,
(q, J = 7.3 Hz, 2 H), 4.58 (q, J = 7.2 Hz, 2 H), 4.81 (t, J = 7.1 Hz,
˜
2
2
1279, 1242, 1225, 1167, 1030 cm–1. MS (ESI+): m/z (%) = 571 [CA/ 2 H) ppm. 13C NMR (500 MHz, CD3CN): δ = 13.54, 13.67, 13.80,
C]+, 211 [C]+ (100), 155 [C – butyl]+, 84. MS (ESI–): m/z (%) = 509
15.37, 19.91, 22.56, 23.76, 28.42, 30.81, 47.25, 57.89, 64.55,
[CA/A]–, 149 (100) [A]–.
162.51 ppm. IR (CH Cl ): ν = 3426, 2963, 2936, 2876, 1535, 1466,
˜
2 2
1167, 1017, 916 cm–1. MS (ESI+): m/z (%) = 547 [CA/C]+, 211
(100) [C]+, 155 [M – butyl]+, 127, 84. MS (ESI–): m/z (%) = 125
[A]–, 111, 97 (100).
1-Butyl-3-ethyl-5-hexyltetrazolium Triflate (31a) and 1-Butyl-4-
ethyl-5-hexyltetrazolium Triflate (31aЈ): Isomeric mixture (1:1).
1
Yield 95% (0.37 g), brown liquid, H NMR (500 MHz, CD3CN):
δ = 0.90 (t, J = J = 7.2 Hz, 3 H), 0.91 (t, J = J = 7.2 Hz, 3 H), 0.97
(t, J = 7.3 Hz, 3 H), 0.98 (t, J = 7.3 Hz, 3 H), 1.32–1.37 (m, 8 H),
1.42–1.51 (m, 8 H), 1.61 (t, J = 7.4 Hz, 3 H), 1.65 (t, J = 7.4 Hz,
3 H), 1.65–1.72 (m, 2 H), 1.82 (quint., J = 7.6 Hz, 2 H), 1.91–2.00
(m, 4 H), 3.03 (t, J = 7.7 Hz, 2 H), 3.16 (t, J = 8.3 Hz, 2 H), 4.48
(t, J = 7.5 Hz, 2 H), 4.49 (t, J = 7.5 Hz, 2 H), 4.54 (q, J = 7.4 Hz,
2 H), 4.81 (q, J = 7.3 Hz, 2 H) ppm. 13C NMR (500 MHz,
CD3CN): δ = 13.49, 13.63, 13.65, 13.99, 14.25, 14.28, 20.06, 20.13,
22.56, 23.08, 23.12, 24.01, 26.53, 26.88, 28.99, 29.48, 30.89, 31.12,
31.81, 31.89, 47.03, 51.06, 51.23, 53.91, 121.64 (q, J = 319.3 Hz,
–CF3), 154.39, 162.61 ppm. 19F NMR (470.2 MHz, CD3CN): δ =
1-Butyl-3-ethyl-5-hexyltetrazolium Ethyl Sulfate (33a) and 1-Butyl-
4-ethyl-5-hexyltetrazolium Ethyl Sulfate (33aЈ): Isomeric mixture
1
(1:1). Yield 73% (0.26 g), pale brown liquid, H NMR (500 MHz,
CD3CN): δ = 0.93 (t, J = 7.1 Hz, 6 H), 0.99 (t, J = 7.4 Hz, 3 H),
1.0 (t, J = 7.3 Hz, 3 H), 1.21 (t, J = 7.1 Hz, 6 H), 1.34–1.39 (m, 8
H), 1.44–1.53 (m, 8 H), 1.63 (t, J = 7.3 Hz, 3 H), 1.68 (t, J =
7.3 Hz, 3 H), 1.67–1.73 (m, 2 H), 1.84 (quint., J = 7.6 Hz, 2 H),
1.94–2.03 (m, 4 H), 3.07 (t, J = 7.7 Hz, 2 H), 3.23 (t, J = 8.3 Hz,
2 H), 3.89 (q, J = 7.1 Hz, 4 H), 4.52 (q, J = 6.9 Hz, 4 H), 4.57 (q,
J = 7.4 Hz, 2 H), 4.84 (q, J = 7.2 Hz, 2 H) ppm. 13C NMR
(500 MHz, CD3CN): δ = 13.49, 13.66, 13.69, 13.98, 14.27, 14.29,
15.50, 20.08, 20.15, 22.65, 23.09, 23.13, 24.04, 26.50, 26.87, 29.02,
29.50, 30.85, 31.09, 31.83, 31.90, 47.00, 51.03, 51.22, 53.85, 63.63
(two coinciding carbon resonances), 154.51, 162.59 ppm. IR
–79.44 (s) ppm. IR (CH Cl ): ν = 3408, 2963, 2936, 2876, 1533,
˜
2
2
1464, 1275, 1225, 1163, 1030 cm–1.
2-Butyl-4-ethyl-5-hexyltetrazolium Triflate (31b): Yield 96%
1
(CH Cl ): ν = 3408, 2959, 2934, 2874, 1535, 1466, 1246, 1225, 1167,
(0.38 g), brown liquid, H NMR (500 MHz, CD3CN): δ = 0.91 (t,
˜
2
2
1020, 916 cm–1.
J = 7.1 Hz, 3 H), 0.97 (t, J = 7.8 Hz, 3 H), 1.32–1.37 (m, 4 H),
1.39–1.48 (m, 4 H), 1.58 (t, J = 7.4 Hz, 3 H), 1.82 (quint., J =
7.6 Hz, 2 H), 2.00–2.06 (m, 2 H), 3.02 (t, J = 7.7 Hz, 2 H), 4.53 (q, J
= 7.3 Hz, 2 H), 4.78 (t, J = 7.3 Hz, 2 H) ppm. 13C NMR (500 MHz,
CD3CN): δ = 13.50, 13.69, 14.27, 19.88, 23.13, 23.99, 26.41, 28.99,
30.85, 31.88, 47.23, 57.92, 121.69 (q, J = 319.3 Hz, –CF3),
162.52 ppm. 19F NMR (470.2 MHz, CD3CN): δ = –79.44 (s) ppm.
2-Butyl-4-ethyl-5-hexyltetrazolium Ethyl Sulfate (33b): Yield 75%
(0.27 g), pale brown liquid, 1H NMR (500 MHz, CD3CN): δ = 0.91
(t, J = 7.5 Hz, 3 H), 0.97 (t, J = 7.4 Hz, 3 H), 1.25 (t, J = 7.1 Hz,
3 H), 1.33–1.36 (m, 4 H), 1.41–1.48 (m, 4 H), 1.59 (t, J = 7.1 Hz,
3 H), 1.82 (quint., J = 7.7 Hz, 2 H), 2.04 (quint., J = 7.4 Hz, 2 H),
3.03 (t, J = 7.6 Hz, 2 H), 4.02 (q, J = 7.1 Hz, 2 H), 4.55 (q, J =
7.3 Hz, 2 H), 4.78 (t, J = 7.2 Hz, 2 H) ppm. 13C NMR (500 MHz,
CD3CN): δ = 13.53, 13.69, 14.29, 15.26, 19.90, 23.13, 24.01, 26.38,
29.00, 30.82, 31.89, 47.25, 57.91, 65.45, 162.52 ppm. IR (CH2Cl2):
IR (CH Cl ): ν = 3414, 2961, 2936, 2876, 1535, 1468, 1277, 1225,
˜
2
2
1163, 1030 cm–1.
General Procedure for the Synthesis of Tetrazolium Ethyl Sulfates
(Table 4): Diethyl sulfate (1.2 mmol) was slowly added with stirring
at ambient temperature to a solution of the appropriate 1,5- (28a,
29a) or 2,5-disubstituted tetrazole (28b, 29b) (1 mmol) in toluene,
followed by stirring under reflux for about 8 h. Upon cooling to
room temp. the corresponding tetrazolium salts separated out as
insoluble liquids. They were further washed with toluene and dried
under reduced pressure and in vacuo at 60 °C to furnish the onium
salts 32a/32aЈ (1:1 isomer mixture), 32b and 33b as room-tempera-
ture ILs.
ν = 3406, 2959, 2934, 2874, 1535, 1462, 1234, 1161, 1044, 860 cm–1.
˜
General Procedure for the Synthesis of Tetrazolium Bis(trifluorome-
thanesulfonyl)imides (Table 4): The metathesis reaction was carried
out by addition of an aqueous solution of Li[NTf2] (1 mmol in
8 mL of deionized H2O) to an aqueous solution of the appropriate
tetrazolium ethyl sulfate 32a/32aЈ, 32b, 33a/33aЈ, or 33b (1 mmol,
8 mL of deionized H2O) and stirred at 30–35 °C. Upon completion
(turbid solution turns to clear, 7–8 h), the onium salts 34a/34aЈ,
34b, 35a/35aЈ, and 35b separated as sticky semi-solids. After re-
peated washing with water, the salts were dissolved in toluene or
MeCN and evaporated to remove the last traces of water. Final
vacuum drying at 80 °C gave colorless semi-solids upon standing
at room temperature.
1,5-Dibutyl-3-ethyltetrazolium Ethyl Sulfate (32a) and 1,5-Dibutyl-
4-ethyltetrazolium Ethyl Sulfate (32aЈ): Isomeric mixture (1:1).
Yield 77% (0.26 g), pale brown liquid, 1H NMR (500 MHz,
CD3CN): δ = 0.98 (t, J = 7.3 Hz, 6 H), 0.99 (t, J = 7.3 Hz, 6 H),
1.20 (t, J = 7.2 Hz, 6 H), 1.42–1.55 (m, 8 H), 1.61–1.70 (m, 2 H),
1.62 (t, J = 7.3 Hz, 3 H), 1.66 (t, J = 7.3 Hz, 3 H), 1.78–1.84 (m,
2 H), 1.92–2.01 (m, 4 H), 3.05 (t, J = 7.7 Hz, 2 H), 3.20 (t, J =
8.2 Hz, 2 H), 3.91 (q, J = 7.2 Hz, 4 H), 4.50 (t, J = 7.6 Hz, 2 H),
4.51 (t, J = 7.5 Hz, 2 H), 4.55 (q, J = 7.2 Hz, 2 H), 4.82 (q, J =
7.3 Hz, 2 H) ppm. 13C NMR (500 MHz, CD3CN): δ = 13.51, 13.66,
13.68, 13.71, 13.80, 13.99, 15.48, 20.1, 20.17, 22.45, 22.57, 23.13,
23.80, 28.58, 28.83, 30.88, 31.10, 47.06, 51.09, 51.28, 53.92, 63.98,
1,5-Dibutyl-3-ethyltetrazolium Bis(trifluoromethanesulfonyl)imide
(34a) and 1,5-Dibutyl-4-ethyltetrazolium Bis(trifluoromethanesul-
fonyl)imide (34aЈ): Isomeric mixture (1:1): Yield 98% (0.48 g), col-
orless semi-solid, m.p. 60 °C. 1H NMR (500 MHz, CD3CN): δ =
0.97 (t, J = 7.3 Hz, 6 H), 0.98 (t, J = 7.3 Hz, 6 H), 1.41–1.55 (m,
8 H), 1.61 (t, J = 7.3 Hz, 3 H), 1.66 (t, J = 7.3 Hz, 3 H), 1.61–1.70
(m, 2 H), 1.77–1.84 (m, 2 H), 1.91–2.00 (m, 4 H), 3.03 (t, J =
7.7 Hz, 2 H), 3.14 (t, J = 8.3 Hz, 2 H), 4.47 (t, J = 7.6 Hz, 2 H),
4.48 (t, J = 7.4 Hz, 2 H), 4.53 (q, J = 7.3 Hz, 2 H), 4.81 (q, J =
7.3 Hz, 2 H) ppm. 13C NMR (500 MHz, CD3CN): δ = 13.53, 13.60,
13.63, 13.65, 13.76, 14.03, 20.07, 20.14, 22.32, 22.54, 23.12, 23.76,
28.61, 28.83, 30.93, 31.15, 47.08, 51.11, 51.27, 53.98, 120.94 (q, J
= 318.4 Hz, –CF3), 154.34, 162.62 ppm. 19F NMR (470.2 MHz,
154.52, 162.62 ppm. IR (CH Cl ): ν = 3433, 2963, 2938, 2876,
˜
2
2
1535, 1466, 1242, 1167, 1017, 916 cm–1. MS (ESI+): m/z (%) = 547
[CA/C]+, 211 (100) [C]+, 155 [C – butyl]+, 84. MS (ESI–): m/z (%)
= 125 [A]–, 97 (100).
2,5-Dibutyl-4-ethyltetrazolium Ethyl Sulfate (32b): Yield 79%
(0.27 g), pale brown liquid, 1H NMR (500 MHz, CD3CN): δ = 0.99
Eur. J. Org. Chem. 2011, 6343–6355
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6353

G. Aridoss, K. K. Laali
FULL PAPER
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CD CN): δ = –80.17 (s) ppm. IR (CH Cl ): ν = 2967, 2940, 2880,
˜
3
2
2
1533, 1468, 1348, 1186, 1136, 1055 cm–1.
2,5-Dibutyl-4-ethyltetrazolium Bis(trifluoromethanesulfonyl)imide
(34b): Yield 97% (0.47 g), colorless semi-solid, m.p. 32 °C. 1H
NMR (500 MHz, CD3CN): δ = 0.97 (t, J = 7.5 Hz, 3 H), 0.98 (t,
J = 7.3 Hz, 3 H), 1.40–1.53 (m, 4 H), 1.59 (t, J = 7.3 Hz, 3 H),
1.78–1.84 (m, 2 H), 2.01–2.07 (m, 2 H), 3.03 (t, J = 7.7 Hz, 2 H),
4.53 (q, J = 7.2 Hz, 2 H), 4.78 (q, J = 7.2 Hz, 2 H) ppm. 13C NMR
(500 MHz, CD3CN): δ = 13.52, 13.72, 13.77, 19.93, 22.57, 23.79,
28.50, 30.88, 47.31, 58.02, 120.98 (q, J = 319.4 Hz, –CF3),
162.58 ppm. 19F NMR (470.2 MHz, CD3CN): δ = –80.13 (s) ppm.
[2]
IR (CH Cl ): ν = 2963, 2936, 2876, 1533, 1468, 1351, 1186, 1136,
˜
2
2
1057 cm–1.
[3]
1-Butyl-3-ethyl-5-hexyltetrazolium
Bis(trifluoromethanesulfonyl)-
imide (35a) and 1-Butyl-4-ethyl-5-hexyltetrazolium Bis(trifluoro-
methanesulfonyl)imide (35aЈ): Isomeric mixture (1:1): Yield 98%
(0.51 gm), colorless semi-solid, m.p. 45 °C. 1H NMR (500 MHz,
CD3CN): δ = 0.91 (t, J = 7.1 Hz, 3 H), 0.92 (t, J = 7.1 Hz, 3 H),
0.98 (t, J = 7.5 Hz, 3 H), 0.99 (t, J = 7.5 Hz, 3 H), 1.32–1.37 (m,
8 H), 1.43–1.51 (m, 8 H), 1.61 (t, J = 7.2, 3 H), 1.66 (t, J = 7.4 Hz,
3 H), 1.65–1.70 (m, 2 H), 1.82 (quint., J = 7.6 Hz, 2 H), 1.91–2.00
(m, 4 H), 3.03 (t, J = 7.6 Hz, 2 H), 3.14 (t, J = 8.3 Hz, 2 H), 4.48
(t, J = 7.5 Hz, 2 H), 4.49 (t, J = 7.5 Hz, 2 H), 4.53 (q, J = 7.2 Hz,
2 H), 4.82 (q, J = 7.3 Hz, 2 H) ppm. 13C NMR (500 MHz,
CD3CN): δ = 13.52, 13.62, 13.65, 14.03, 14.26, 14.29, 20.08, 20.15,
22.55, 23.10, 23.14, 24.04, 26.56, 26.92, 29.01, 29.52, 30.93, 31.18,
31.81, 31.90, 47.10, 51.13, 51.29, 53.99, 120.96 (q, J = 318.9 Hz, –
CF3), 154.37, 162.66 ppm. 19F NMR (470.2 MHz, CD3CN): δ =
[4]
[5]
[6]
[7]
[8]
[9]
J. He, B. Li, F. Chen, Z. Xu, G. Yin, J. Mol. Catal. A 2009,
304, 135–138.
–80.12 (s) ppm. IR (CH Cl ): ν = 2963, 2936, 2876, 1466, 1351,
˜
2
2
1188, 1136, 1057 cm–1. MS (ESI+): m/z (%) = 757 [CA/C]+, 239 [10]
J. Bonnamour, C. Bolm, Chem. Eur. J. 2009, 15, 4543–4545.
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Chem. Int. Ed. 2010, 122, 7255–7259.
(100) [C]+, 183 [C – butyl]+, 155. MS (ESI–): m/z (%) = 799 ([C]+
[11]
and 2[A]–), 280 (100) [A]–.
[12]
2-Butyl-4-ethyl-5-hexyltetrazolium
Bis(trifluoromethanesulfonyl)-
imide (35b): Yield 98% (0.51 g), colorless semi-solid, m.p. 36 °C.
1H NMR (500 MHz, CD3CN): δ = 0.91 (t, J = 7.1 Hz, 3 H), 0.97
(t, J = 7.5 Hz, 3 H), 1.32–1.37 (m, 4 H), 1.39–1.48 (m, 4 H), 1.58
(t, J = 7.2 Hz, 3 H), 1.82 (quint., J = 7.4 Hz, 2 H), 2.00–2.06 (m,
2 H), 3.02 (t, J = 7.7 Hz, 2 H), 4.52 (q, J = 7.3 Hz, 2 H), 4.78 (t,
J = 7.2 Hz, 2 H) ppm. 13C NMR (500 MHz, CD3CN): δ = 13.49,
13.72, 14.26, 19.88, 23.13, 23.98, 26.43, 28.99, 30.86, 31.87, 47.24,
57.96, 120.93 (q, J = 318.8 Hz, -CF3), 162.53 ppm. 19F NMR
[13]
[14]
F. Alonso, Y. Moglie, G. Radivoy, M. Yus, Tetrahedron Lett.
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V. Engels, F. Benaskar, N. Patil, E. V. Rebrov, V. Hessel, L. A.
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X. Ma, J. X. Wang, S. Li, K. H. Wang, D. Huang, Tetrahedron
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(470.2 MHz, CD CN): δ = –80.19 (s) ppm. IR (CH Cl ): ν = 2963,
˜
3
2
2
2936, 2876, 1533, 1468, 1348, 1186, 1136, 1055 cm–1. MS (ESI+):
m/z (%) = 757 [CA/C]+, 239 [C]+ (100), 183 [C – butyl]+, 155. MS
(ESI–): m/z (%) = 799 ([C]+ and 2[A]–), 280 (100) [A]–.
ˇ
[17]
[18]
B. H. Lipshutz, D. M. Nihan, E. Vinogradova, B. R. Taft, Z. V.
Supporting Information (see footnote on the first page of this arti-
cle): NMR spectra and the 2D NMR correlations for representative
compounds.
Bosˇkovic´, Org. Lett. 2008, 10, 4279–4282.
Acetonitrile and propionitrile did not react. Similar results
(Ͻ5% conversion) with propionitrile and isopropyl nitrile in
the presence of tungstates were reported in ref.[9]
Similar results were reported previously (see ref.[21]) for p-ami-
no- and o-aminobenzonitrile in the presence of NaN3/montmo-
rillonitrile K-10 or kaolin.
[19]
[20]
Acknowledgments
We thank the University of North Florida for support, Dr. Nelson
Zhao of this department for NMR assistance, and Dr. Mahinda
Gangoda (Kent State University) for recording the ES-MS spectra.
a) K. K. Laali, V. J. Gettwert, J. Org. Chem. 2001, 66, 35–40;
b) K. K. Laali, V. J. Gettwert, J. Fluorine Chem. 2001, 107, 31–
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Received: June 30, 2011
Published Online: September 27, 2011
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