Synthesis of azidochloromethane and azidobromomethane

Article abstract of DOI:10.1016/j.tetlet.2010.03.094

By treatment of tris(azidomethyl)amine with dry hydrogen halide, azidochloromethane and azidobromomethane were prepared. The former product, which is more stable than the latter, was isolated as a colorless liquid. The desired azidohalomethanes are intermediates in the nucleophilic substitution of dihalomethanes to generate diazidomethane but could not be detected in this transformation.

Full text of DOI:10.1016/j.tetlet.2010.03.094

Tetrahedron Letters 51 (2010) 2880–2882
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Tetrahedron Letters
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Synthesis of azidochloromethane and azidobromomethane
a
b
b
b
Klaus Banert a, , Young-Hyuk Joo , Tobias Rüffer , Bernhard Walfort , Heinrich Lang
*
a Chemnitz University of Technology, Organic Chemistry, Strasse der Nationen 62, 09111 Chemnitz, Germany
b Chemnitz University of Technology, Inorganic Chemistry, Strasse der Nationen 62, 09111 Chemnitz, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
By treatment of tris(azidomethyl)amine with dry hydrogen halide, azidochloromethane and azidobro-
momethane were prepared. The former product, which is more stable than the latter, was isolated as a
colorless liquid. The desired azidohalomethanes are intermediates in the nucleophilic substitution of
dihalomethanes to generate diazidomethane but could not be detected in this transformation.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 15 March 2010
Accepted 22 March 2010
Available online 27 March 2010
Keywords:
Azides
Hazardous compounds
Nucleophilic substitution
Triazoles
The family of simple azidomethanes was completely character-
ized starting with the early work on methyl azide published by
Dimroth and Wislicenus.1 Diazidomethane (3) and triazidome-
thane were generated from methylene chloride (1a) or bromide
(1b) and bromoform, respectively (Scheme 1). These transforma-
tions were performed by Hassner and co-workers with the help
of a polymeric azide reagent.2 Recently, tetraazidomethane was
isolated as a dangerous explosive colorless liquid.3
If dichloromethane (1a) is used as a solvent in the synthesis of
azides, the unwanted formation of hazardous compound 3 is pos-
sible.2,4 Thus, several explosions were reported and attributed to
the surprising generation of diazide 3.5 Azidochloromethane (2a)
was included into the corresponding warnings although this com-
pound, like azidobromomethane (2b), was never detected or pre-
pared by another method (Scheme 1).6 However, the equilibrium
structure and the force constants of 2a were calculated in the
MNDO approximation.7 In this Letter, we report the synthesis
and characterization of azides 2a,b.
By NMR analysis of the transformation1a?3, Hassner recognized
already that no signal of intermediate 2a could be registered.2b He
assumed that the second displacement on 2a probably proceeded
faster than the first chlorine substitution. Thus, we started with
the mixed dihalomethane 1c and hoped that the iodine displace-
mentstep1c?2awouldnotbe significantlyslowerthanthereaction
2a?3. However, wecouldnotdetectanytraceof2a, whentreatment
of 1c with a substoichiometric amount of hexadecyltributylphos-
phonium azide8 in chloroform was monitoredby NMR spectroscopy,
which led quantitatively and under mild conditions (18 h at 20 °C) to
the diazide 3.
After this frustration, we thought that the synthesis of 2a and
2b can only be successful if the halide is introduced after the for-
mation of the azido group by nucleophilic substitution. Thus, we
reacted triazide 4b9 (Scheme 2), which is easily accessible from tri-
chloride 4a,10 with dry hydrogen chloride in chloroform or hexane
(20 min at 20 °C) to obtain a mixture of 2a and 3 after workup (so-
lid, anhydrous K2CO3, and re-condensation). These products could
be separated conveniently by preparative gas chromatography
(packed column, 1 m, Carbowax, 30 °C) to get 2a and 3 as explosive
colorless liquids (caution!).11 When the mixture of 2a and 3,
resulting from 4b and hydrogen chloride, was worked up and then
treated with cyclooctyne,12 the triazoles 8a (11% based on 4b), 9,
and 10 were isolated. Cycloaddition product 10 could be prepared
quantitatively (based on 3) if an excess of cyclooctyne was used. All
new compounds were characterized by the usual spectroscopic
data,13 and the structure of 8a was additionally confirmed by
single crystal X-ray diffraction analysis (Fig. 1).14 When 4b was
reacted with an excess of phenylsulfenyl chloride15 (chloroform,
20 °C) instead of hydrogen chloride, the formation of 2a (8%), 3
(21%), and 4a (60%) was observed. Other
a-azido amines such as
716,17 could also be utilized to generate mixtures of 2a and 3.
However, the yield of 2a (61%) was rather low. Treatment of 4b
with hydrogen bromide in anhydrous tetrachloromethane or
* Corresponding author. Tel.: +49 371 531 31463; fax: +49 371 531 21229.
E-mail address: klaus.banert@chemie.tu-chemnitz.de (K. Banert).
Scheme 1.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.03.094

K. Banert et al. / Tetrahedron Letters 51 (2010) 2880–2882
2881
Scheme 2.
indicated unambiguously the structures of 1H-1,2,3-triazoles. In
contrast to this, cycloaddition of 4b at cyclooctyne is accompanied
by a rapid rearrangement reaction leading to the 2H-1,2,3-triazoles
5 (17% yield) and 6 (25%). The molecular structure of 5 was con-
firmed by single crystal X-ray diffraction analysis (Fig. 1).14
In conclusion, we have shown that azidochloromethane (2a)
and azidobromomethane (2b) can be synthesized from triazide
4b. Possibly, these products are able to enrich the multifarious
chemistry of organic azides.18
References and notes
1. Dimroth, O.; Wislicenus, W. Ber. Dtsch. Chem. Ges. 1905, 38, 1573–1576.
2. (a) Hassner, A.; Stern, M. Angew. Chem. 1986, 98, 479–480. Angew. Chem., Int. Ed.
Engl. 1986, 25, 478–479; (b) Hassner, A.; Stern, M.; Gottlieb, H. E.; Frolow, F. J.
Org. Chem. 1990, 55, 2304–2306.
3. Banert, K.; Joo, Y.-H.; Rüffer, T.; Walfort, B.; Lang, H. Angew. Chem. 2007, 119,
1187–1190. Angew. Chem., Int. Ed. 2007, 46, 1168–1171.
4. (a) Bretherick, L. Chem. Eng. News 1986, 64, 2; (b) am Ende, D. J.; Vogt, P. F. Org.
Process Res. Dev. 2004, 8, 1045–1048; (c) Fotsing, J. R.; Banert, K. Eur. J. Org.
Chem. 2005, 3704–3714; (d) Fotsing, J. R.; Hagedorn, M.; Banert, K. Tetrahedron
2005, 61, 8904–8909; (e) Beckmann, H. S. G.; Wittmann, V. Org. Lett. 2007, 9, 1–
4; (f) Fotsing, J. R.; Banert, K. Synthesis 2006, 261–272.
5. (a) Dharanipragada, R.; VanHulle, K.; Bannister, A.; Bear, S.; Kennedy, L.; Hruby,
V. J. Tetrahedron 1992, 48, 4733–4748; (b) Peet, N. P.; Weintraub, P. M. Chem.
Eng. News 1993, 71, 4; (c) Hruby, V. J.; Boteju, L.; Li, G. Chem. Eng. News 1993, 71,
2; (d) Peet, N. P.; Weintraub, P. M. Chem. Eng. News 1994, 72, 4; (e) Conrow, R.
E.; Dean, W. D. Org. Process Res. Dev. 2008, 12, 1285–1286.
Figure 1. ORTEP diagrams (50% probability level) of the molecular structures of 8a
(above) and 5 (below). For 5, disordered atoms have been omitted for clarity.
6. Titz, A.; Radic, Z.; Schwardt, O.; Ernst, B. Tetrahedron Lett. 2006, 47, 2383–2385.
7. Glidewell, C.; Holden, H. D. J. Mol. Struct. (THEOCHEM) 1982, 89, 325–332.
8. Review: Banert, K. Synthesis 2007, 3431–3446.
9. Klapötke, T. M.; Krumm, B.; Scherr, M.; Steemann, F. X.; Banert, K.; Joo, Y.-H.
Chem. Eur. J. 2009, 15, 11341–11345.
10. (a) Fluck, E.; Meiser, P. Angew. Chem. 1971, 83, 721–722. Angew. Chem., Int. Ed.
Engl. 1971, 10, 653; (b) Fluck, E.; Meiser, P. Chem. Zeit. 1971, 95, 922; (c) Fluck,
E.; Meiser, P. Chem. Ber. 1973, 106, 69–77.
chloroform (4 °C, 30 min) led to the bromo compound 2b, which
was less stable than 2a and could only be characterized in solu-
tion.13 Cycloadduct 8b was isolated in 14% yield, when 4b was re-
acted with hydrogen bromide followed by conversion with
cyclooctyne. NMR data13 of the heterocycles 8a, 8b, 9, and 10

2882
K. Banert et al. / Tetrahedron Letters 51 (2010) 2880–2882
11. Caution should be exercised during isolation of explosive azides. Especially, 2a,
2b, and 3 are dangerous compounds, which should be handled in solution.
12. Tietze, L. F.; Eicher, T. Reaktionen und Synthesen im Organisch-Chemischen
Praktikum und Forschungslaboratorium, 2nd ed.; Thieme: Stuttgart, 1991, p 40.
= 2095 cmÀ1 (N3), 1235
~
m
1.48–1.53 (m, 2H), 1.68–1.75 (m, 2H), 1.85–1.91 (m, 2H), 2.80–2.83 (m, 2H),
2.85–2.89 (m, 2H), 5.93 (s, 2H). 13C NMR (CDCl3): d = 21.59 (t), 24.26 (t), 24.49
(t), 25.55 (t), 25.86 (t), 27.65 (t), 38.60 (t, 1JCH = 169.8 Hz), 133.78 (s), 145.67 (s).
MS (ESI) m/z (%) = 244.1 (100) [M+H, 79Br]+, 246.1 (90) [M+H, 81Br]+. HR MS
(ESI) m/z = 244.0496 [calcd C9H14BrN3 244.0444].
13. Azidochloromethane (2a): Colorless liquid. IR (CDCl3):
(N3). 1H NMR (CDCl3): d = 5.00 (s, 2H). 13C NMR (CDCl3): d = 61.43 (t,
1JCH = 171.2 Hz).
1-Azidomethyl-4,5,6,7,8,9-hexahydro-1H-cycloocta-1,2,3-triazole (9): Colorless
À1
liquid. IR (CDCl3):
= 2101 cm (N3), 1234 (N3). 1H NMR (CDCl3): d = 1.43–
~
m
À1
(N3). 1H NMR (CDCl3):
1.56 (m, 4H), 1.73–1.81 (m, 2H), 1.81–1.87 (m, 2H), 2.79–2.83 (m, 2H), 2.90–
~
m
Azidobromomethane (2b): IR (CDCl3):
= 2138 cm
d = 4.99 (s, 2H). 13C NMR (CDCl3): d = 50.05 (t, JCH = 173.5 Hz).
2.94 (m, 2H), 5.50 (s, 2H). 13C NMR (CDCl3): d = 21.39 (t), 24.43 (t), 24.73 (t),
1
1
Tris-[(4,5,6,7,8,9-hexahydro-2H-cycloocta-1,2,3-triazol-2-yl)methyl]amine
(5):
25.85 (t), 26.28 (t), 28.04 (t), 61.05 (t, JCH = 158.0 Hz), 133.46 (s), 145.69 (s).
~
white solid. Mp: 86–89 °C. IR (CDCl3):
m
= 2935 cmÀ1, 2856, 2238. 1H NMR
Bis-(4,5,6,7,8,9-hexahydro-1H-cycloocta-1,2,3-triazol-1-yl)methane (10): Colorless
(CDCl3): d = 1.43 (m, 12H), 1.69 (br. m, 12H), 2.73 (m, 12H), 5.54 (s, 6H). 13C
crystals. Mp: 149–152 °C. IR (CDCl3):
= 2934 cmÀ1, 2858, 2236. 1H NMR
~
m
1
NMR (CDCl3): d = 23.63 (t), 25.39 (t), 28.47 (t), 69.26 (tquin, JCH = 152.9 Hz,
(CDCl3): d = 1.32–1.41 (m, 8H), 1.55–1.63 (m, 4H), 1.67–1.75 (m, 4H), 2.83–2.87
(m, 4H), 2.93–2.97 (m, 4H), 6.61 (s, 2H). 13C NMR (CDCl3): d = 21.29 (t), 24.35
(t), 24.78 (t), 25.65 (t), 26.21 (t), 27.97 (t), 57.71 (t, 1JCH = 155.2 Hz), 134.44 (s),
145.92 (s). MS (ESI) m/z (%) = 315.2 (100) [M+H]+. C17H26N6 (314.44) calcd: C,
64.94; H, 8.33; N, 26.73; found: C, 64.76; H, 8.42; N, 25.87.
3JCH = 4.6 Hz), 146.32 (s). MS (ESI) m/z (%) = 545.4 (100) [M+K]+. C27H42N10
(506.70) calcd: C, 64.00; H, 8.35; N, 27.64; found: C, 63.80; H, 8.32; N, 27.09.
Azidomethyl-{bis-[(4,5,6,7,8,9-hexahydro-2H-cycloocta-1,2,3-triazol-2-yl)methyl]}
= 2935 cmÀ1, 2857, 2106 (N3). 1H NMR
~
m
amine (6): yellow liquid. IR (CDCl3):
(CDCl3): d = 1.40 (m, 8H), 1.67 (m, 8H), 2.75 (m, 8H), 4.44 (s, 2H), 5.37 (s, 4H).
13C NMR (CDCl3): d = 23.49 (t), 25.25 (t), 28.46 (t), 68.16 (t), 68.91 (t), 146.94 (s).
1-Chloromethyl-4,5,6,7,8,9-hexahydro-1H-cyclÀo1octa-1,2,3-triazole (8a): Colorless
1H NMR (CDCl3): d = 1.41–1.56
~
m = 3118 cm .
14. CCDC-767597 (8a) and CCDC-767598 (5) contain the supplementary
crystallographic data and can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
15. Barrett, A. G. M.; Dhanak, D.; Graboski, G. G.; Taylor, S. J. Org. Synth. Coll. Vol.
1993, 8, 550–551.
crystals. Mp: 63 °C. IR (CDCl3):
(m, 4H), 1.70–1.78 (m, 2H), 1.84–1.92 (m, 2H), 2.83–2.92 (m, 4H), 5.94 (s, 2H).
13C NMR (CDCl3): d = 21.46 (t), 24.32 (t), 24.59 (t), 25.83 (t), 25.87 (t), 27.78 (t),
16. Böhme, H.; Morf, D. Chem. Ber. 1958, 91, 660–662.
17. We prepared 7 from (N,N-dimethyl)methyleneammonium chloride and
1
52.82 (t, JCH = 167.2 Hz), 133.81 (s), 145.73 (s). MS (ESI) m/z (%) = 200.1 (18)
[M+H]+, 363.2 (100) [2 M – Cl]+. C9H14N3Cl (199.69) calcd: C, 54.14; H, 7.07; N,
21.04; found: C, 54.77; H, 7.16; N, 20.54.
sodium azide in dichloromethane (20 °C, 30 min, then reflux, 2 h) with 97%
yield.
1-Bromomethyl-4,5,6,7,8,9-hexahydro-1H-cycloocta-1,2,3-triazole (8b): Colorless
= 2935 cmÀ1, 2858. 1H NMR (CDCl3): d = 1.38–1.44 (m, 2H),
~
m
18. Organic Azides – Syntheses and Applications; Bräse, S., Banert, K., Eds.; John
Wiley & Sons Ltd: Chichester, 2009.
oil. IR (CDCl3):