Synthesis of aminotetrazolyl esters from cyanogen azide with amino esters

Article abstract of DOI:10.1002/ejoc.201201153

Several α-amino esters (and their hydrochloride salts) were treated with cyanogen azide at ambient temperature in a mixture of water and acetonitrile to form chiral 5-aminotetrazole derivatives in good yields (47-69 %). The cyanogen azide was prepared from cyanogen bromide and sodium azide. Other functionalized α-amino esters (cysteine, arginine, histidine, and serine) were formed in only trace amounts and were difficult to purify by column chromatography. All 5-aminotetrazoles (i.e., 1-8) were characterized by IR spectroscopy, ¹H, ¹³C, and ¹⁵N NMR spectroscopy, and elemental analysis. The structures of 3-7 were obtained by single-crystal X-ray structure analysis. 5-Aminotetrazolyl esters were prepared by a reaction between cyanogen azide and an amino ester to give 1-substituted aminotetrazoles in good yields. Compounds were fully characterized, and the structures of 3-7 were supported by single-crystal X-ray structure analysis. Heats of formation for all compounds were calculated by the Gaussian 03 program and differential scanning calorimetry. Copyright

Full text of DOI:10.1002/ejoc.201201153

FULL PAPER
DOI: 10.1002/ejoc.201201153
Synthesis of Aminotetrazolyl Esters from Cyanogen Azide with Amino Esters
Young-Hyuk Joo,*[a] Soo Gyeong Cho,[b] Eun Mee Goh,[b] Damon A. Parrish,[c] and
Jean’ne M. Shreeve*[d]
Keywords: Synthetic methods / Nitrogen heterocycles / Azides / Amines
Several α-amino esters (and their hydrochloride salts) were
treated with cyanogen azide at ambient temperature in a
mixture of water and acetonitrile to form chiral 5-amino-
tetrazole derivatives in good yields (47–69%). The cyanogen
azide was prepared from cyanogen bromide and sodium az-
ide. Other functionalized α-amino esters (cysteine, arginine,
histidine, and serine) were formed in only trace amounts and
were difficult to purify by column chromatography. All 5-
aminotetrazoles (i.e., 1–8) were characterized by IR spec-
troscopy, 1H, 13C, and 15N NMR spectroscopy, and elemental
analysis. The structures of 3–7 were obtained by single-crys-
tal X-ray structure analysis.
1- and 2-alkylated-5-aminotetrazoles. Separating the iso-
mers was realized by fractional crystallization or fractional
distillation, but in low yields. In the past few years, the most
convenient route to 1-substituted 5-aminotetrazoles was
through the addition of a primary amine to cyanogen azide,
which was an efficient reagent under noncatalytic mild con-
ditions.[6]
Herein, we describe the work leading to a series of 5-
aminotetrazole derivatives of α-(5-aminotetrazolyl) esters.
5-Aminotetrazole esters may be of interest as a new class
of organo materials or biologically active organic materials,
which are realized in good yields through straightforward
routes.
Introduction
Currently, as the most widely used type of tetrazole or
aminotetrazole, substituted aminotetrazoles have been in-
vestigated for their use in bioorganic[1] and inorganic mate-
rials[2] as well as for their interesting applications to such
matters as high energy density materials (HEDMs).[3] In re-
cent years, many research groups have reported on a variety
of applications for effective organocatalysts such as the
tetrazole or triazole analogue of proline.[4] Many different
synthetic methods and applications are known for substi-
tuted tetrazoles and are of considerable interest for medici-
nal and biological uses. Because of the importance of sub-
stituted tetrazoles, the development of new synthetic ap-
proaches with special reaction conditions continues to be
an active area of research.
Results and Discussion
In 1969, the first investigation into the synthesis of ester-
substituted aminotetrazoles led to their generation through
alkylation of the triethylammonium salt of tetrazole with
either ethyl bromoacetate or methyl chloroacetate.[5] How-
ever, the selective alkylation of aminotetrazoles was not
possible because of the competitive formation between the
The previously reported synthesis of 5-aminotetrazole
compounds through the reaction of cyanogen azide[7] with
primary or secondary amines is very useful for the prepara-
tion of highly energetic materials.[6,8] We found that a vari-
ety of α-amino esters served as versatile intermediates for
the synthesis of 1-substituted 5-aminotetrazoles, which
could be used for biologically active organic materials. Syn-
thetic reactions to give functionalized aminotetrazoles have
now been extended by employing an excellent in situ
method that involves reactions between cyanogen azide and
primary amines (see Scheme 1).
At ambient temperature, the α-amino ester or its hydro-
chloride was dissolved in a mixture of water/acetonitrile in
the presence of cyanogen azide, which was synthesized at
0 °C from cyanogen bromide and dry sodium azide in dry
acetonitrile, and was cleanly converted into the aminotet-
razolyl ester (see Scheme 1). In cases where the amino acid
was protected by a methyl or ethyl group and was not un-
usually hindered, the reaction yields were 47–69% (1[5a]
(47%), 2 (60%), 3 (69%), 4 (65%), 5 (61%), 6 (56%), 7
[a] Department of Energetic Materials & Pyrotechnics, Hanwha
Corporation Defence R&D Center,
Daejeon, 305-156, Korea
Fax: +82-42-8292623
E-mail: joo2011@hanwha.co.kr
Homepage: www.hanwha.com
[b] Defense Advanced R&D Center, Agency for Defense
Development,
Daejeon 305-600, Korea
[c] Naval Research Laboratory, Code 6030
Washington, DC 20375-5001, USA
[d] Department of Chemistry, University of Idaho,
Moscow, ID 83844-2343, USA
Fax: +1-208-8859146
E-mail: jshreeve@uidaho.edu
Homepage: www.webpages.uidaho.edu/~jshreeve
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201201153.
688
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 688–692

Synthesis of Aminotetrazolyl Esters
(53%), 8 (68%)]. The attractiveness of this route stems from
the ease with which the amino ester precursors can undergo
a one-step synthesis to form the aminotetrazole derivatives.
Unfortunately, other functionalized amino esters (e.g., cys-
teine, serine, arginine, and histidine) were formed in only
trace amounts and are purified with great difficulty using
column chromatography. In contrast to other products,
compound 5 formed the R enantiomer during the reaction.
All of the α-(aminotetrazolyl) esters were characterized by
the usual spectroscopic methods, and in the case of 3–7,
characterization was done by single-crystal X-ray diffrac-
tion analysis (see Figure 1).
Data collection was performed, and the unit cell was ini-
tially refined using APEX2 (v 2.1-0).[9a] The data reduction
was performed using SAINT (v. 7.34A)[9b] and XPREP
(v. 2005/2).[9c] Corrections were applied for Lorentz, polar-
ization, and absorption effects using SADABS (v. 2004/
1).[9d] The structure was solved and refined with the aid of
the programs from the SHELXTL-plus (v. 6.12) system of
programs.[9e] The full-matrix least-squares refinement on F2
included the atomic coordinates and anisotropic thermal
parameters for all of the non-hydrogen atoms. The H atoms
were included using a riding model. Selected data and pa-
rameters for the X-ray determinations are given in Table 1.
The crystallographic data obtained for 3–7 were compared
to those for 5-amino-1-vinyltetrazole[10] and 1,5-diaminote-
trazole (see Table 1 and Figure 1).[11,12] Not surprisingly the
bond lengths for N-4–C-5 [1.345(6) Å] and C-5–N-15
[1.346(6) Å] of 6, for example, are nearly equal, because the
approximate planar geometry of the 5-amino group results
from the considerable conjugation in the N-4–C-5–N-15
fragment. However, the bond length of N-2–N-3
Scheme 1. Synthesis of 5-aminotetrazol-1-yl esters by cyclization.
For the synthesis of 5*, neutral l-tyrosine methyl ester was used.
Figure 1. Single-crystal X-ray diffraction analysis of 5-aminotetrazole derivatives 3–7.
Eur. J. Org. Chem. 2013, 688–692
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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689

Y.-H. Joo, J. M. Shreeve et al.
FULL PAPER
Table 1. Crystallographic data for 3–7.
3
4
5
6
7
Empirical formula
Formula weight
Space group
a [Å]
b [Å]
c [Å]
C6H11N5O2
185.20
C2
14.548(3)
10.364(2)
12.129(3)
90
C8H15N5O2
213.25
P212121
5.9590(12)
8.9155(18)
42.852(9)
90
C11H13N5O3
263.26
P212121
6.6796(13)
11.582(2)
15.963(3)
90
C7H13N5O2S
231.28
P212121
5.515(5)
9.037(5)
22.386(8)
90
C7H11N5O4
229.21
P212121
6.0246(4)
7.0045(4)
24.8977(16)
90
α [°]
β [°]
99.691(3)
90
1802.6(7)
8
90
90
2276.6(8)
8
90
90
1234.9(4)
4
90
90
90
90
γ [°]
V [Å3]
1115.6(12)
4
1050.67(11)
4
Z
λ [Å]
T [K]
0.71073
100(2)
1.365
0.71073
100(2)
1.224
0.71073
100(2)
1.416
0.71073
173(2)
1.377
0.71073
293(2)
1.449
Dcalcd. [gcm–3]
μ [mm–1]
R1 [I Ͼ 2σ (I)][a]
wR2 [I Ͼ 2σ (I)][b]
CCDC number[c]
0.106
0.093
0.107
0.281
0.120
0.0308
0.0758
892135
0.0367
0.0842
892136
0.0286
0.0725
892137
0.0549
0.0989
892138
0.0375
0.0952
892139
2 2
[a] R1 = Σ||Fo| – |Fc||/Σ|Fo|. [b] wR2 = {Σ[w(Fo2 – Fc ) ]/Σ[w(Fo2)2]}1/2. [c] CCDC contains the supplementary crystallographic data for this
paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
[1.305(5) Å] is slightly shorter than the adjacent single to tetrazole appear at the highest field in all of the spectra.
bonds of N-1–N-2 [1.364(5) Å] and N-3–N-4 [1.363(5) Å]. In the coupled 15N NMR spectrum for compound 5, the
The bond lengths of N-2–N-3 for structures 3–7 lie between N-5 resonance is a triplet (1JN,H = 88 Hz), as expected. The
1.280(14) and 1.305(5) Å, which are typical values observed signals for N-2 and N-3 appear at the lowest field because
for 5-aminotetrazoles. The amino group in 6b forms an of electronegativity effects. The assignments were made on
intermolecular interaction because of the weak hydrogen the basis of the literature values for the chemical shifts of
bonding of N-15···N-3_#1 [3.873(6) Å; symmetry transfor- aminotetrazole.[6,8]
mation used to generate equivalent atoms: #1 = x – 1/2,
The calculations for the heats of formation, which is one
–y + 5/2, –z.].
of the important characteristics for aminotetrazoles, were
In Figure 2, the 15N NMR spectra of aminotetrazole de- performed by using the Gaussian 03 (Revision D.01) pro-
rivatives 3–5 and 7 were measured in CD3CN or [D6]- gram.[13] The geometric optimization of the structures and
DMSO solution, and the chemical shifts are given with re- frequency analyses were carried out by using the B3LYP
spect to CH3NO2 as the external standard. In each 15N functional with the 6-31+G** basis set,[14] and single-point
NMR spectrum, there are the five signals for the amino- energies were calculated at the MP2/6-311++G** level. All
tetrazole. The signals for the amine group (i.e., N-5) bonded of the optimized structures were characterized as true local
energy minima on the potential-energy surface without
imaginary frequencies. The heats of formation for the com-
pounds were computed by using the method of isodesmic
reactions (see Supporting Information). The enthalpy of an
isodesmic reaction (ΔHr298°) was obtained by combining
the MP2/6-311++G** energy difference for the reaction,
the scaled zero-point energies (B3LYP/6-31+G**), and
other thermal factors (B3LYP/6-31+G**).
Table 2. Physical properties of aminotetrazolyl esters 1–8.
Compound
Yield
[% ]
Density[a]
[gcm–3]
M.p.[b]
[°C]
ΔHf[c]
[kJmol–1]
1
2
3
4
5
6
7
8
47
60
69
65
61
56
53
68
–
–
188
151
130
166
159
88
–59.08
–93.21
–132.27
–171.61
–177.80
13.96
1.365
1.224
1.416
1.377
1.449
–
134
166
–452.54
192.78
[a] Calculated from X-ray structural data. [b] DSC. [c] Determined
by using Gaussian 03.
Figure 2. 15N NMR spectra of 3–5 and 7.
690
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Eur. J. Org. Chem. 2013, 688–692

Synthesis of Aminotetrazolyl Esters
Ethyl 2-(5-Amino-1H-tetrazol-1-yl)acetate (2): White solid (60%);
Tetrazole compounds (1–5 and 7) exhibited negative
heats of formation, whereas 6 and 8 had positive heats of
formation (see Table 2). All of the tetrazoles were studied
by differential scanning calorimetry (DSC), which showed
that 1–8 had melting points between 88 and 188 °C (see
Table 2). The densities of most of the new aminotetrazoles
ranged between 1.224 and 1.449 gcm–3, which were deter-
mined by single-crystal X-ray structure analysis.
m.p. 151 °C. IR (KBr): ν = 3368, 3266, 3164, 2999, 2961, 2907,
˜
1744, 1651, 1591, 1492, 1376, 1229, 1098, 1024 cm–1. 1H NMR
(300 MHz, [D6]DMSO): δ = 6.80 (s, 2 H, NH2), 5.10 (s, 2 H, CH2),
4.17 (q, 3J = 7.1 Hz, 2 H, CH2), 1.21 (t, 3J = 7.1 Hz, 3 H,
CH3) ppm. 13C NMR (75.5 MHz, [D6]DMSO): δ = 166.6, 156.1,
61.5, 45.8, 13.9 ppm. C5H9N5O2 (171.16): calcd. C 35.09, H 5.30,
N 40.92; found C 34.93, H 5.25, N 41.19.
Ethyl (S)-2-(5-Amino-1H-tetrazol-1-yl)propanoate (3): White solid
(69%); m.p. 130 °C. [α]2D0 = –96.7 (c = 1.0, DMSO). IR (KBr): ν =
˜
3332, 3185, 2985, 1744, 1652, 1589, 1225, 1084, 1023 cm–1. 1H
3
NMR (300 MHz, [D6]DMSO): δ = 6.74 (s, 2 H, NH2), 5.27 (q, J
Conclusions
= 7.3 Hz, 1 H, CH), 4.14 (dq, 2J = 2.4 Hz, 3J = 7.1 Hz, 2 H, CH2),
1.71 (d, 3J = 7.3 Hz 3 H, CH3), 1.17 (t, 3J = 7.1 Hz, 3 H, CH3) ppm.
In summary, under noncatalytic mild conditions, cyano-
gen azide was an efficient reagent for the synthesis of read- 13C NMR (75.5 MHz, [D6]DMSO): δ = 168.7, 155.7, 61.6, 52.9,
16.1, 13.9 ppm. 15N NMR (50.7 MHz, [D6]DMSO): δ = 12.8,
ily purified 1-substituted 5-aminotetrazoles from primary
–19.4, –84.7, –129.1, –168.0, –332.5 ppm. C6H11N5O2 (185.18):
amino esters. The general procedure described herein is ap-
calcd. C 38.91, H 5.99, N 37.82; found C 38.69, H 6.07, N 37.94.
plicable to both amino esters and other primary amines to
lead, in each case, to the preparation of 5-aminotetrazole
derivatives in good yields.
The structure of 3 was supported by single-crystal X-ray structure
analysis.
Methyl (S)-2-(5-Amino-1H-tetrazol-1-yl)-4-methylpentanoate (4):
White solid (65%); m.p. 166 °C. [α]2D0 = –63.3 (c = 1.0, DMSO). IR
(KBr): ν = 3338, 3161, 2961, 2872, 1757, 1653, 1592 cm–1. 1H
˜
NMR (300 MHz, [D6]DMSO): δ = 6.83 (s, 2 H, NH2), 5.25 (dd, 3J
Experimental Section
3
= 4.1 Hz, J = 11.2 Hz, 1 H, CH), 3.69 (s, 3 H, OCH3), 2.25 (m, 1
Safety Precautions: Pure cyanogen azide is extremely dangerous
and toxic. When utilizing the substance as a reactant, it must al-
ways be dissolved in a solvent as a dilute solution. During the reac-
tion, trace amounts of moisture resulted in the formation of the
sodium 5-azidotetrazolate byproduct, and this highly explosive and
shock-sensitive solid was subsequently isolated.[7,15] Manipulations
must be carried out in a fume hood. Any excess amount of cyano-
gen azide in acetonitrile may be destroyed by adding it to tri-
phenylphosphane or norbornene.[16]
H, Ha), 1.95 (m, 1 H, Hb), 1.29 (m, 1 H), 0.86 (s, 3 H, CH3), 0.84
(s, 3 H, CH3) ppm. 13C NMR (75.5 MHz, [D6]DMSO): δ = 169.2,
156.0, 55.6, 52.8, 38.3, 24.3, 22.5, 20.6 ppm. 15N NMR (50.7 MHz,
[D6]DMSO): δ = 12.3, –16.4, –83.5, –129.1, –167.3, –332.9 ppm.
C8H15N5O2 (213.24): calcd. C 45.06, H 7.09, N 32.84; found C
44.97, H 7.09, N 31.86. The structure of 4 was supported by single-
crystal X-ray structure analysis.
Methyl (R)-2-(5-Amino-1H-tetrazol-1-yl)-3-(4-hydroxyphenyl)prop-
anoate (5): At 0 °C, cyanogen bromide (10 mmol) was dissolved in
dry acetonitrile (50 mL). To this solution was added dry sodium
azide (40 mmol). The reaction mixture was stirred at 0 °C for 4 h.
The inorganic salt was removed by filtration. (Caution! After fil-
tration, the salt was quickly dissolved in cold water.) The cyanogen
azide solution was added to a solution containing l-tyrosine methyl
ester (5.0 mmol) in acetonitrile (50 mL) at 0 °C. After stirring over-
night at ambient temperature, the solvent was allowed to evaporate
into the air. The product was purified by washing it with water and
acetonitrile to give 5 (61%) as a light yellow solid; m.p. 159 °C.
1
General Methods: H, 13C, and 15N NMR spectroscopic data were
recorded at 300.13, 75.48, and 50.69 MHz, respectively, with
300 MHz (Bruker AVANCE 300) and 500 MHz (Bruker AVANCE
500) spectrometers. CD3CN or [D6]DMSO was used as the solvent
and locking solvent. The melting and decomposition points were
obtained with a differential scanning calorimeter (TA Instruments
Company, Model Q10) at a scan rate of 10 °Cmin–1. IR spectra
were recorded, using KBr pellets for solids, with a BIORAD model
3000 FTS spectrometer. Elemental analyses were determined using
an Exeter CE-440 elemental analyzer.
[α]2D0 = –1.59 (c = 1.0, DMSO). IR (KBr): ν = 3465, 3319, 3255,
˜
General Procedure: At 0 °C, cyanogen bromide (10 mmol) was dis-
solved in dry acetonitrile (50 mL). To this solution was added dry
sodium azide (40 mmol). The reaction mixture was stirred at 0 °C
for 4 h. The inorganic salt was removed by filtration. (Caution! Af-
ter filtration, the salt was quickly dissolved in cold water.) The
cyanogen azide solution was added to a solution containing the
amino ester (for 1–4, 6, and 7, 5.0 mmol; for 8, 2.5 mmol) in water
(15 mL) at 0 °C. [For the ammonium chloride, NaOH (4.5 mmol)
was required.] After stirring overnight at ambient temperature, the
solvent was allowed to evaporate into the air. The product was
purified by washing it with water and acetonitrile.
3198, 3018, 2957, 2897, 2815, 2751, 2693, 2619, 1761, 1641, 1516,
1464, 1283, 1249, 1229, 1175 cm–1. 1H NMR (300 MHz, [D6]-
DMSO): δ = 9.24 (br. s, 1 H, OH), 6.89–6.92 (AAЈXXЈ system, 2
H, Ar), 6.66 (s, 2 H, NH2), 6.60–6.63 (AAЈXXЈ system, 2 H, Ar),
5.46 (dd, J = 4.8 Hz, J = 10.8 Hz, 1 H, CH), 3.71 (s, 3 H, CH3),
3.30–3.48 (m, 2 H, CH2) ppm. 13C NMR (75.5 MHz, [D6]DMSO):
δ = 168.4, 156.2, 156.0, 129.8, 125.9, 115.2, 58.6, 52.9, 34.9 ppm.
15N NMR (50.7 MHz, [D6]DMSO): δ = 8.1 (N-3), –23.6 (N-2),
–90.9 (N-4), –174.5 (m, N-1), –333.4 (t, 1J = 88 Hz, NH2) ppm.
C11H13N5O3 (263.25): calcd. C 50.19, H 4.98, N 26.60; found C
49.89, H 4.82, N 26.07. The structure of 5 was supported by single-
crystal X-ray structure analysis.
3
3
Methyl 2-(5-Amino-1H-tetrazol-1-yl)acetate (1): White solid (47%);
m.p. 188 °C. IR (KBr): ν = 3335, 3250, 3153, 2988, 2950, 1737,
(S)-Methyl 2-(5-Amino-1H-tetrazol-1-yl)-4-(methylthio)butanoate
(6): Colorless crystals (56%); m.p. 88 °C. [α]2D0 = –10.6 (c = 1.0,
˜
1
1659, 1643, 1589, 1491, 1412, 1377, 1236, 990, 813 cm–1. H NMR
(300 MHz, [D6]DMSO): δ = 6.80 (s, 2 H, NH2), 5.12 (s, 2 H, CH2),
DMSO). IR (KBr): ν = 3329, 3171, 2952, 2923, 1751, 1648, 1579,
˜
3.71 (s, 3 H, CH3) ppm. 13C NMR (75.5 MHz, [D6]DMSO): δ = 1440, 1296, 1275, 1236, 1179, 1123 cm–1. 1H NMR (300 MHz,
167.1, 156.1, 52.5, 45.7 ppm. C4H7N5O2 (157.13): calcd. C 30.58,
H 4.49, N 44.57; found C 30.36, H 4.35, N 44.22.
[D6]DMSO): δ = 6.82 (s, 2 H, NH2), 5.35 (m, 1 H), 3.69 (s, 3 H,
OCH3), 2.31–2.54 (m, 4 H), 2.03 (s, 3 H, SCH3) ppm. 13C NMR
Eur. J. Org. Chem. 2013, 688–692
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(75.5 MHz, [D6]DMSO): δ = 168.7, 156.2, 56.0, 52.9, 29.3 (2 C),
14.4 ppm. C7H13N5O2S (231.28): calcd. C 36.35, H 5.67, N 30.28;
found C 36.41, H 5.67, N 29.82. The structure of 6 was supported
by single-crystal X-ray structure analysis.
(S)-Dimethyl 2-(5-Amino-1H-tetrazol-1-yl)succinate (7): White solid
(53%); m.p. 134 °C. [α]2D0 = –67.6 (c = 1.0, DMSO). IR (KBr): ν =
˜
3344, 3173, 2963, 1747, 1661, 1588, 1469, 1439, 1375, 1290, 1236,
1174, 1085, 1015, 988, 858 cm–1. 1H NMR (300 MHz, [D6]DMSO):
3
3
δ = 6.90 (s, 2 H, NH2), 5.55 (dd, J = 7.5 Hz, J = 7.6 Hz, 1 H),
3
3.69 (s, 3 H, OCH3), 3.60 (s, 3 H, OCH3), 3.30 (d, J = 7.7 Hz, 2
H) ppm. 13C NMR (75.5 MHz, [D6]DMSO): δ = 169.6, 167.7,
155.9, 53.6, 53.0, 51.9, 34.6 ppm. 15N NMR (50.7 MHz, [D6]-
DMSO): δ = 11.3, –17.6, –84.5, –129.1, –164.2, –332.6 ppm.
C7H11N5O4 (229.19): calcd. C 36.68, H 4.84, N 30.56; found C
36.13, H 4.69, N 30.16. The structure of 7 was supported by single-
crystal X-ray structure analysis.
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Methyl 2,6-Bis(5-amino-1H-tetrazol-1-yl)hexanoate (8): White solid
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Madison, Wisconsin, 2004; e) SHELXTL, v. 6.12b, Bruker
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(68%); m.p. 166 °C. IR (KBr): ν = 3349, 3175, 2953, 1753, 1656,
˜
1588, 1457, 1270, 1212, 1122, 1080, 1005 cm–1. 1H NMR
(300 MHz, [D6]DMSO): δ = 6.82 (s, 2 H, NH2), 6.64 (s, 2 H, NH2),
3
5.24 (dd, 3J = 7.4 Hz, J = 7.4 Hz, 1 H), 4.04 (t, 3J = 7.1 Hz, 2 H),
3.67 (s, 3 H, OCH3), 2.17–2.24 (m, 2 H, CH2), 1.71 (m, 2 H), 1.12–
1.32 (m, 2 H) ppm. 13C NMR (75.5 MHz, [D6]DMSO): δ = 168.7,
156.1, 155.2, 56.9, 52.7, 44.0, 29.4, 27.6, 22.2 ppm. C9H16N10O2
(296.29): calcd. C 36.48, H 5.44, N 47.27; found C 36.35, H 5.49,
N 47.31.
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Supporting Information (see footnote on the first page of this arti-
cle): 1H and 13C NMR spectra of tetrazoles 1–8, isodesmic reaction
scheme, and computational data.
Acknowledgments
The authors gratefully acknowledge the support of the Office of
Naval Research, Dr. Clifford Bedford (grant number N00014-10-
0097) and the Agency for Defense Development (Korea).
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Received: August 24, 2012
Published Online: December 7, 2012
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