PAPER
Syntheses of 5-Amino-1-aryltetrazoles
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Anal. Calcd for C8H8ClN5O6 (305.6): C, 31.44; H, 2.64; N, 22.91.
Found: C, 31.52; H, 2.69; N, 22.79.
Anal. Calcd for C10H13N5O (219.2): C, 54.78; H, 5.98; N, 31.94.
Found: C, 54.61; H, 5.95; N, 31.99.
1-Aryl-4-tert-butyltetrazolium Perchlorates 7d–f; General
Procedure
N-Methyl-1-(4-nitrophenyl)-1H-tetrazol-5-amine (9c)
Yield: 67%; mp 284–286 °C (dec.).
A solution of 1-aryltetrazole 2 (2.0 mmol) and 1,1-dimethylethanol
(450 mg, 6.1 mmol) in HClO4 (70%, 2 mL) was kept at r.t. for 5 d.
The mixture was diluted with H2O (10 mL) and cooled to 10 °C. The
precipitate was filtered, washed with H2O and Et2O and dried at re-
duced pressure to furnish the tetrazolium salts 7d–f that were used
in the next stage without further purification.
1H NMR (DMSO-d6): d = 2.92 (d, J = 4.6 Hz, 3 H, CH3), 7.21 (q,
J = 4.5 Hz, 1 H, NH), 7.90 (d, J = 8.9 Hz, 2 H, Ar), 8.44 (d, J = 9.0
Hz, 2 H, Ar).
13C NMR (DMSO-d6): d = 30.1, 124.6, 125.0, 138.1, 146.8, 155.2.
Anal. Calcd for C8H8N6O2 (220.2): C, 43.64; H, 3.66; N, 38.17.
Found: C, 43.62; H, 3.70; N, 38.04.
4-tert-Butyl-1-phenyl-1H-tetrazolium Perchlorate (7d)
Yield: 97% (contains ca. 16% of 1,3-isomer).
1H NMR (CD3CN): d = 1.86 (s, 9 H, t-C4H9), 7.74–7.94 (m, 5 H,
Ar), 10.61 (s, 1 H, CH).
13C NMR (CD3CN): d = 29.1, 31.3, 118.4, 123.4, 131.7, 133.5,
140.2.
N-tert-Butyl-1-phenyl-1H-tetrazol-5-amine (9d)
Yield: 62%; mp 114–115 °C (Lit.5e mp 113–114 °C).
N-tert-Butyl-1-(4-ethoxyphenyl)-1H-tetrazol-5-amine (9e)
Yield: 65%; mp 141–143 °C.
1H NMR (DMSO-d6): d = 1.36 (t, J = 6.9 Hz, 3 H, CH3), 1.37 (s, 9
H, t-C4H9), 4.10 (q, J = 6.8 Hz, 2 H, CH2), 6.14 (s, 1 H, NH), 7.11
(d, J = 8.4 Hz, 2 H, Ar), 7.43 (d, J = 8.3 Hz, 2 H, Ar).
Anal. Calcd for C11H15ClN4O4 (302.7): C, 43.64; H, 4.99; N, 18.51.
Found: C, 43.53; H, 5.08; N, 18.47.
13C NMR (DMSO-d6): d = 14.3, 28.1, 51.8, 63.3, 115.1, 125.8,
126.2, 153.6, 158.8.
4-tert-Butyl-1-(4-ethoxyphenyl)-1H-tetrazolium Perchlorate
(7e)
Yield: 99% (contains ca. 26% of 1,3-isomer).
Anal. Calcd for C13H19N5O (261.3): C, 59.75; H, 7.33; N, 26.80.
Found: C, 59.62; H, 7.26; N, 26.67.
1H NMR (CD3CN): d = 1.42 (t, J = 7.0 Hz, 3 H, CH3), 1.84 (s, 9 H,
t-C4H9), 4.17 (q, J = 7.0 Hz, 2 H, CH2), 7.21 (d, J = 9.1 Hz, 2 H,
Ar), 7.81 (d, J = 9.2 Hz, 2 H, Ar), 10.48 (s, 1 H, CH).
13C NMR (CD3CN): d = 14.8, 28.9, 32.4, 65.3, 116.9, 118.2, 125.0,
125.1, 146.7.
N-tert-Butyl-1-(4-nitrophenyl)-1H-tetrazol-5-amine (9f)
Yield: 61%; mp 183–185 °C (darkens), 205–207 °C (melts with
dec.).
1H NMR (DMSO-d6): d = 1.40 (s, 9 H, t-C4H9), 6.75 (s, 1 H, NH),
7.90 (d, J = 8.8 Hz, 2 H, Ar), 8.44 (d, J = 8.8 Hz, 2 H, Ar).
13C NMR (DMSO-d6): d =28.5, 52.7, 125.4, 125.5, 139.1, 147.3,
159.9.
Anal. Calcd for C13H19ClN4O5 (346.8): C, 45.03; H, 5.52; N, 16.16.
Found: C, 45.17; H, 5.54; N, 16.11.
4-tert-Butyl-1-(4-nitrophenyl)-1H-tetrazolium Perchlorate (7f)
Yield: 95% (contains <1% of 1,3-isomer).
1H NMR (CD3CN): d = 1.87 (s, 9 H, t-C4H9), 8.17 (d, J = 9.3 Hz, 2
H, Ar), 8.57 (d, J = 9.3 Hz, 2 H, Ar), 10.76 (s, 1 H, CH).
13C NMR (CD3CN): d = 28.7, 68.3, 118.0, 124.3, 126.8, 140.5.
Anal. Calcd for C11H14N6O2 (262.3): C, 50.38; H, 5.38; N, 32.04.
Found: C, 50.34; H, 5.36; N, 31.91.
1-Methyl-N-(4-nitrophenyl)-1H-tetrazol-5-amine (10c)
Yield: 78%; mp 284–286 °C (dec.).
Anal. Calcd for C11H14ClN5O6 (347.7): C, 38.00; H, 4.06; N, 20.14.
Found: C, 37.89; H, 4.10; N, 20.02.
1H NMR (DMSO-d6): d = 3.99 (s, 3 H, CH3), 7.86 (d, J = 9.2 Hz, 2
H, Ar), 8.27 (d, J = 9.2 Hz, 2 H, Ar), 10.17 (s, 1 H, NH).
13C NMR (DMSO-d6): d = 32.1, 116.0, 124.6, 140.2, 145.5, 151.1.
5-Aminotetrazoles 9a–f, 10c, 10f; General Procedure
A stirred mixture of tetrazolium salt 7a–f (1.5 mmol), NaN3 (3.0
mmol, 195 mg) and triethylammonium chloride (3.0 mmol, 414
mg) in MeCN (2 mL) was treated dropwise with DMSO (2 mL). On
the completion of vigorous gas evolution, the mixture was heated to
70 °C and stirred at this temperature for 2 h. In the syntheses of the
compounds 10c and 10f, the temperature was kept at 85 °C for 4 h.
The mixture was allowed to cool and diluted with brine (40 mL).
The precipitate was filtered, washed with H2O and dried at reduced
pressure to give 5-aminotetrazole. Analytical samples were ob-
tained after recrystallization from i-PrOH.
Anal. Calcd for C8H8N6O2 (220.2): C, 43.64; H, 3.66; N, 38.17.
Found: C, 43.73; H, 3.62; N, 38.22.
1-tert-Butyl-N-(4-nitrophenyl)-1H-tetrazol-5-amine (10f)
Yield: 69%; mp 205–207 °C (dec.).
1H NMR (DMSO-d6): d = 1.70 (s, 9 H, t-C4H9), 7.46 (d, J = 9.2 Hz,
2 H, Ar), 8.19 (d, J = 9.2 Hz, 2 H, Ar), 9.26 (s, 1 H, NH).
13C NMR (DMSO-d6): d = 28.0, 60.3, 116.0, 125.0, 140.2, 147.7,
150.3.
Anal. Calcd for C11H14N6O2 (262.3): C, 50.38; H, 5.38; N, 32.04.
Found: C, 50.44; H, 5.29; N, 32.00.
N-Methyl-1-phenyl-1H-tetrazol-5-amine (9a)
Yield: 60%; mp 133–134 °C (Lit.5e mp 133–134 °C).
1-(4-Ethoxyphenyl)-N-methyl-1H-tetrazol-5-amine (9b)
Yield: 92%; mp 155–157 °C.
References
(1) For reviews of tetrazole chemistry, see: (a) Butler, R. N. In
Comprehensive Heterocyclic Chem. II, Vol. 4; Katritzky, A.
R.; Rees, C. W.; Scriven, E. F. V., Eds.; Pergamon: Oxford,
1996, 621. (b) Wittenberger, S. J. Org. Prep. Proced. Int.
1994, 26, 499. (c) Herr, R. J. Bioorg. Med. Chem. 2002, 10,
3379. (d) Voitekhovich, S. V.; Gaponik, P. N.; Ivashkevich,
O. A. Russ. Chem. Rev. 2002, 71, 721.
1H NMR (DMSO-d6): d = 1.35 (t, J = 6.9 Hz, 3 H, CH3), 2.85 (d,
J = 4.6 Hz, 3 H, CH3), 4.10 (q, J = 6.9 Hz, 2 H, CH2), 6.70 (q,
J = 4.4 Hz, 1 H, NH), 7.11 (d, J = 8.8 Hz, 2 H, Ar), 7.43 (d, J = 8.7
Hz, 2 H, Ar).
13C NMR (DMSO-d6): d = 14.4, 30.1, 63.5, 115.3, 125.6, 126.3,
155.7, 159.1.
Synthesis 2006, No. 8, 1307–1312 © Thieme Stuttgart · New York