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
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