1-Substituted 5-aminotetrazoles: Syntheses from CNN3 with primary amines

Article abstract of DOI:10.1021/ol8019742

(Chemical Equation Presented) 1-Substituted 5-aminotetrazoles were prepared in situ by an excellent reaction of cyanogen azide and primary amines to generate an imidoyl azide as an intermediate in acetonitrile/water. After cyclization, the intermediate ga

Full text of DOI:10.1021/ol8019742

ORGANIC
LETTERS
2008
Vol. 10, No. 20
4665-4667
1-Substituted 5-Aminotetrazoles:
Syntheses from CNN3 with Primary
Amines
Young-Hyuk Joo and Jean’ne M. Shreeve*
Department of Chemistry, UniVersity of Idaho, Moscow, Idaho 83844-2343
jshreeVe@uidaho.edu
Received August 23, 2008
ABSTRACT
1-Substituted 5-aminotetrazoles were prepared in situ by an excellent reaction of cyanogen azide and primary amines to generate an imidoyl
azide as an intermediate in acetonitrile/water. After cyclization, the intermediate gave 1-substituted aminotetrazole in good yield. This protocol
also was utilized in the syntheses of bis- and tris(1-substituted 5-aminotetrazole) derivatives.
Aminotetrazoles are an interesting class of heterocycles that
exhibit an unusually wide range of applications such as high
energy density materials (HEDM),1 useful ligands in coor-
dination chemistry,2 in bioorganic chemistry,3 and as drugs
in pharmaceuticals.4 Additionally, aminotetrazoles have
proven to be valuable for the preparation of their substituted
analogues5 and other nitrogen-containing heterocycles.6
More than 120 years ago, 1-substituted 5-aminotetrazole
derivatives were prepared by the treatment of potassium
aminotetrazolate with an alkyl halide.7 In 1932, further
investigation into the synthesis of methyl aminotetrazoles
led to their generation through the high-temperature cycload-
dition of sodium azide to monomethyl-thiourea in alcohol.8
There are several reports in the literature describing the in
situ generation of 1-substituted aminotetrazoles via the
(1) (a) Singh, R. P.; Verma, R. D.; Meshri, D. T.; Shreeve, J. M. Angew.
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Angew. Chem., Int. Ed. 2008, 47, 3330–3347. (c) Singh, R. P.; Gao, H.;
Meshri, D. T.; Shreeve, J. M. In High Energy Density Materials; Klapo¨tke,
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T. M. In High Energy Density Materials; Klapo¨tke, T. M., Ed.; Springer:
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Naud, D. L. 2001, US 6214139; Chem. Abstr. 2001, 134, 282929. (d)
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Weigand, J. Inorg. Chem. 2005, 44, 8044–8052.
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Krause, B. R.; Stanfield, R. L.; Dominick, M. A.; Neub, M. J. Med. Chem.
1996, 39, 4382–4395. (b) Bavetsias, V.; Marriott, J. H.; Melin, C.; Kimbell,
R.; Matusiak, Z. S.; Boyle, F. T.; Jackman, A. L. J. Med. Chem. 2000, 43,
1910–1926. (c) Upadhayaya, R. S.; Jain, S.; Sinha, N.; Kishore, N.; Chandra,
R.; Arora, S. K. Eur. J. Med. Chem. 2004, 39, 579–592. (d) Castro, J. L.;
Ball, R. G.; Broughton, H. B.; Russell, M. G. N.; Rathbone, D.; Watt, A. P.;
Baker, R.; Chapman, K. L.; Fletcher, A. E.; Smith, S. J.; Marshall, G. R.;
Ryecroft, W.; Matassa, V. G. J. Med. Chem. 1996, 39, 842–849.
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nakrishnareddy, G. Tetrahedron Lett. 2007, 48, 7038–7041. (b) Purchase,
C. F., II; White, A. D.; Anderson, M. K.; Bocan, T. M. A.; Bousley, R. F.;
Hamelehle, K. L.; Homan, R.; Krause, B. R.; Lee, P.; Mueller, S. B.; Speyer,
C.; Stanfield, R. L.; Reindel, J. F. Bioorg. Med. Chem. Lett. 1996, 6, 1753–
1758. (c) Yamazaki, K.; Hasegawa, H.; Umekawa, Ueki, K.; Y.; Ohashi,
N.; Kanaoka, M. Bioorg. Med. Chem. Lett. 2002, 12, 1275–1278. (d) Vieira,
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62b, 1343–1352. (c) Geisberger, G.; Klapo¨tke, T. M.; Stierstorfer, J. Eur.
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10.1021/ol8019742 CCC: $40.75
Published on Web 09/25/2008
2008 American Chemical Society

alkylation of 5-aminotetrazole with alkyl halides. However,
selective alkylation of aminotetrazoles is not possible because
of the competitive formation of 1- and 2-alkylated-5-
aminotetrazoles.4a,9 These isomers were separable by crystal-
lization or column chromatography in very low yields.
Another method for the synthesis of mono-, di-, and
trisubstituted 5-aminotetrazoles is described using the mer-
cury(II)-promoted attack of an azide anion on a thiourea.10
The reaction proceeds through a guanyl azide intermediate
which subsequently undergoes cyclization to the tetrazole.
Di- and trisubstituted (benzotriazolyl)-carboximidamides
from (benzotriazolyl)carboximidoyl chlorides (various sub-
stituents as alkyl, aryl, or heteroaryl) with sodium azide
provide access to 1,N,N-trisubstituted 5-aminotetrazoles.5
Reactions were performed at room temperature, and the
aminotetrazole derivatives were obtained in 41-90% yield.
Many methods for the synthesis of substituted aminotetra-
zoles are known,11 but due to their importance, the develop-
ment of new synthetic approaches using special reaction
conditions continues as an active research area.
Scheme 1. Addition of a Primary Amine to Cyanogen Azide
through the Intermediacy of an Imidoyl Azide and 1-Substituted
5-Aminotetrazoles
Recently, we have reported energetic nitrogen-rich
derivatives of 1,5-diaminotetrazole generated in situ from
cyanogen azide12,13 and hydrazine derivatives.14 However,
amine derivatives are more suitable (commercial and inex-
pensive) and provide a variety of useful starting materials
as possible replacements for 1,5-diaminotetrazoles. Our
continuing interest in the development of 1-substituted
5-aminotetrazole compounds, which can be used for high-
energy density materials or biologically active organic
materials, has now been extended by the utilization of an
excellent in situ method which involves reactions of cyano-
gen azide and primary amines (Scheme 1).
The commercially available amine compounds were
reacted with 2-3 equiv of cyanogen azide dissolved in
acetonitrile/water solution (4:1) to give initially the
imidoyl azide as an intermediate. Subsequent cyclization
of the intermediate led to the 1-substituted monoaminotet-
razoles 1-7 in good yields [17 (61%), 29b (53%), 3 (70%),
4 (73%), 5 (74%), 6 (62%), 7 (52%)]. It is important to
note that the synthesis of cyanogen azide from cyanogen
bromide and sodium azide in dry acetonitrile should be
performed with extreme care12b,14 (see Supporting Informa-
tion).
It is noteworthy that the current method can be
efficiently applied to the preparation of bis(1-substituted-
5-aminotetrazoles). Diamine compounds with 5-6 equiv
of cyanogen bromide and excess sodium azide led to
products in good yields [89c (71%), 99c (84%), 10 (73%),
11 (72%), 12 (79%)] of bis(aminotetrazole) 8-12. Re-
moval of the acetonitrile/water solvent from the reaction
mixture by air drying is followed by additional washing
with acetonitrile and water (1:4). The structures of all
(8) Stolle, R.; Ehrmann, K.; Rieder, D.; Wille, H.; Winter, H.; Henke-
Stark, F. J. Prak. Chem. 1932, 134, 282–309.
(9) (a) Henry, R. A.; Finnegan, W. G J. Am. Chem. Soc. 1954, 76, 926–
928. (b) Finnegan, W. G.; Henry, R. A J. Org. Chem. 1959, 24, 1565–
1567. (c) Barmin, M. I.; Gromova, S. A.; Mel’nikov, V. V. Russ. J. Appl.
Chem. 2001, 74, 1156–1163.
1
aminotetrazole derivatives are supported by IR and H,
13C{1H}, and 15N NMR spectroscopic data as well as
(10) Batey, R. A.; Powell, D. A. Org. Lett. 2000, 2, 3237–3240.
(11) (a) Finnegan, W. G.; Henry, R. A.; Lieber, E. J. Org. Chem. 1953,
18, 779–791. (b) Percival, D. F.; Herbst, R. M J. Org. Chem. 1957, 22,
925–933. (c) Norris, W. P.; Henry, R. A. J. Org. Chem. 1964, 29, 650–
660. (d) Demko, Z. P.; Sharpless, K. B. J. Org. Chem. 2001, 66, 7945–
7950. (e) Himo, F.; Demko, Z. P.; Noodleman, L.; Sharpless, K. P. J. Am.
Chem. Soc. 2003, 125, 9983–9987. (f) Butler, R. N.; Scott, F. L J. Org.
Chem. 1966, 31, 3182–3187. (g) Peet, N. P J. Heterocycl. Chem. 1987, 24,
223–225.
1
elemental analysis (see Supporting Information). The H
and 13C{1H} NMR spectra for 11 could not be recorded
owing to its poor solubility in deuterated solvent. The
three-substituted aminotetrazole 13 was obtained by
reacting cyanogen azide with tris(aminoethyl)amine in
water/acetonitrile using an analogous procedure (yield:
54%).
(12) (a) Marsh, F. D.; Hermes, M. E. J. Am. Chem. Soc. 1964, 86, 4506–
4507. (b) Marsh, F. D. J. Org. Chem. 1972, 37, 2966–2969. (c) McMurry,
J. E.; Coppolino, A. P. J. Org. Chem. 1973, 38, 2821–2827. (d) Banert, K.;
Joo, Y.-H.; Ru¨ffer, T.; Walfort, B.; Lang, H. Angew. Chem., Int. Ed. 2007,
46, 1168–1171.
In Figure 1, the 15N NMR spectra of 6 (top) at -333.89,
-162.15, -89.60, -24.54, -7.32 ppm and 13 (bottom)
with six signals at -351.98, -334.39, -173.92, -89.30,
-20.52, and 6.87 are depicted. The signals of the primary
amine appear as expected at high field in spectra with
(13) Cyanogen azide, a colorless oil, was first isolated from the reaction
of sodium azide and cyanogen chloride. The synthesis of cyanogen azide
from sodium azide and cyanogen bromide and its reaction and characteriza-
tion as well as handling were reported.12a
(14) Joo, Y.-H.; Twamley, B.; Garg, S.; Shreeve, J. M. Angew. Chem.,
Int. Ed. 2008, 47, 6236–6239.
1
1
triplets (6: JN,H ) 87 Hz; 13: JN,H ) 87 Hz). The
4666
Org. Lett., Vol. 10, No. 20, 2008

difference for the reaction, the scaled zero points energies
(B3LYP/6-31+G**), and other thermal factors (B3LYP/
6-31+G**). All of the 1-substituted 5-aminotetrazoles
exhibit positive heats of formation with 2-13 having
values between 33.3 and 863.7 kJ·mol-1. Density is one
of the most important physical properties of energetic
materials. The densities of most of the new aminotetra-
zoles range between 1.294 and 1.585 g·cm-3. By using
the experimental values for the densities of the 5-ami-
notetrazoles, 2-13, the detonation pressures (P) and
velocities (D) were calculated based on traditional
Chapman-Jouget thermodynamic detonation theory using
Cheetah 4.0 and 5.0 (see Supporting Information).17 For
compounds 8-13, the calculated detonation pressures lie
in the range between 14.61 and 19.88 GPa (comparable
to TNT ) 19.5 GPa and ADN ) 23.7 GPa). Detonation
velocities are found between 7177 and 7719 ms-1 (com-
parable to TNT ) 6881 m·s-1 and ADN ) 8074 m·s-1).
For initial safety testing, the impact sensitivity was tested
according to BAM methods.18 All compounds are insensi-
tive toward impact with sensitivities >40 J (comparable
to TNT ) 15 J and TATB ) 50 J).
In conclusion, we have developed a new method for the
efficient preparation of 1-substituted 5-aminotetrazoles from
cyanogen azide and amines. The reaction conditions for the
formation of the final 1-substituted 5-aminotetrazoles are
mild, and purification is simple. This synthesis of aminotet-
razole derivatives could be utilized to prepare a variety of
bioorganic compounds or organocatalysts as ligands. We are
currently focusing our attention on efforts to discover
compounds with high nitrogen content via this cyclization
reaction and on application of the reaction for efficient
syntheses of compounds that are useful for HEDM.
Figure 1.
15N NMR spectra of 6 and 13 (delay of 10 s between
pulses).
assignments are given based on the values of the chemical
shifts of substituted aminotetrazole on comparison with
the literature.11e,14,15 For compound 13, the N2 resonance
(t, 3JN,H ) 1.6 Hz, N2) is split into triplets due to the coupling
with the protons of -CH2-. The N1 resonance was shown
as slightly broadened by coupling with protons of ethylene.
The signal for the N3 resonance was a singlet with no proton
coupling observed.
The heats of formation for 2-13 were calculated with
Gaussian 0316 and are summarized in Table 1. These
values were computed by using the method of isodesmic
reactions. The enthalpy of an isodesmic reaction (∆Hr298
)
is obtained by combining the MP2/6-311+G** energy
Acknowledgment. The authors gratefully acknowledge the
support of DTRA (HDTRA1-07-1-0024), NSF (CHE-0315275),
and ONR (N00014-06-1-1032).
Table 1. Physical Properties of 1-Substituted 5-Aminotetrazole
Derivatives 2-13
Supporting Information Available: The experimental
procedures, analytical data, and NMR spectra of products.
This material is available free of charge via the Internet at
http://pubs.acs.org.
a
c
yield
[%]
Tm
[°C]
densityb
∆fH°298
∆fH°298
[kJ·g-1
]
compd
[g·cm-3
]
[kJ·mol-1
]
2
3
4
5
6
7
8
9
10
11
12
13
53
70
73
74
62
52
71
84
73
72
79
54
160
166
202
159
193
194
274
287
1.511
1.503
1.294
1.432
1.398
1.382
1.567
1.567
1.585
1.460
1.453
1.492
33.3
226.7
213.8
226.7
260.2
300.7
536.6
513.9
323.2
454.7
436.5
863.7
0.258
1.97
1.40
1.37
1.38
1.72
2.74
2.44
1.43
1.82
1.74
2.47
OL8019742
(15) (a) Berger, S.; Braun, S.; Kalinowski, H.-O. NMR-Spektroskopie
Von Nichtmetallen, Band 2,15N-NMR-Spektroskopie, Georg Thieme Verlag,
Stuttgart: New York, 1992; pp 36-38. (b) Orendt, A. M.; Michl, J.; Reiter,
J. Magn. Reson. Chem. 1989, 27, 1–3.
(16) Frisch, M. J., et al. Gaussian 03, revision D.01. See Supporting
Information for full reference.
(17) (a) Fried, L. E.; Glaesemann, K. R.; Howard, W. M.; Souers, P. C.
CHEETAH 4.0 User’s Manual; Lawrence Livermore National Laboratory,
2004. (b) Bastea, S.; Fried, L. E.; Glaesemann, K. R.; Howard, W. M.;
Souers, P. C.; Vitello, P. A. CHEETAH 5.0 User’s Manual; Lawrence
Livermore National Laboratory, 2007.
256
346(dec.)
242
(18) (a) www.bam.de. (b) A portion of 20 mg of aminotetrazoles 2-13
was subjected to a drop-hammer test using a 10 kg weight dropped 40 cm
height. A range in impact sensitivities from reference: Galvez-Ruiz, J. C.;
Holl, G.; Karaghiosoff, K.; Klapötke, T. M.; Loehnwitz, K.; Mayer, P.;
Noeth, H.; Polborn, K.; Rohbogner, C. J.; Suter, M.; Weigand, J. J. Inorg.
Chem. 2005, 44, 4237-4253. (Insensitive > 40 J; less sensitive g 35 J;
sensitive g 4 J; very sensitive e 3 J).
123
a Thermal decomposition temperature under nitrogen gas (DSC, 10
°C/min). b Gas pycnometer (25 °C). c Heat of formation (using 83.68
kJ·mol-1 for the enthalpy of sublimation for each compound; calculated
via Gaussian 03).
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