A mild and efficient method for the preparation of acyl azides from carboxylic acids using triphosgene

Article abstract of DOI:10.1016/S0040-4039(01)02377-2

An efficient use of triphosgene for the preparation of various acyl azides from carboxylic acids and sodium azide is described.

Full text of DOI:10.1016/S0040-4039(01)02377-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 1345–1346
A mild and efficient method for the preparation of acyl azides
from carboxylic acids using triphosgene
V. K. Gumaste, B. M. Bhawal and A. R. A. S. Deshmukh*
Division of Organic Chemistry (Synthesis), National Chemical Laboratory, Pune 411 008, India
Received 8 October 2001; revised 5 December 2001; accepted 14 December 2001
Abstract—An efficient use of triphosgene for the preparation of various acyl azides from carboxylic acids and sodium azide is
described. © 2002 Elsevier Science Ltd. All rights reserved.
Over the last few years triphosgene [bis(trichloro-
methyl)carbonate] has emerged as a versatile synthetic
auxiliary for the synthesis of some important classes of
organic compounds.1 This white crystalline compound
has proved to be safe and advantageous in comparison
with its gaseous congener, phosgene. In our recent
communication2 we have reported an efficient use of
triphosgene as an acid activator in the construction of
b-lactam rings by ketene–imine cycloaddition reactions.
In this communication we wish to report the applica-
tion of triphosgene as a reagent for the preparation of
various acyl azides from carboxylic acids and sodium
azide under very mild reaction conditions.
few reports on the direct conversion of carboxylic acids
to acyl azides by using acid activators such as ethyl
chloroformate,7 diphenylphosphoryl azide (DDPA),8
phenyldichlorophosphate,9 SOCl2–DMF10 and NCS–
triphenylphosphine.11
Triphosgene is known to react with acids to produce
acid chlorides or anhydrides.12 We have successfully
employed this reagent for the direct conversion of acids
to acyl azides (Scheme 1). Various aryl as well as alkyl
carboxylic acids on reaction with triphosgene in the
presence of sodium azide and triethylamine undergo
smooth conversion to the corresponding acyl azides in
very good yields (Table 1). This method was found to
be very mild, efficient, and general as any acid could be
easily converted to its acyl azide without a Curtius
rearrangement leading to an isocyanate. The addition
of triethylamine is essential as no acyl azide formation
was observed in the absence of triethylamine.
Acyl azides are valuable synthetic intermediates.3 They
are useful for the preparation of amides and they
undergo facile thermal rearrangement to isocyanates.
Various amines, urethanes and ureas can be easily
obtained from isocyanates. Acyl azides are usually pre-
pared from acid derivatives such as acid halides and
acyl hydrazides.3,4 The combinations of chromic anhy-
dride–trimethylsilyl azide5 and triazidochlorosilane-
active manganese dioxide6 have been reported for the
preparation of acyl azides from aldehydes. There are a
Typical experimental procedure for the preparation of
benzoyl azide: To a stirred solution of benzoic acid
(0.61 g, 5 mmol) and sodium azide (0.65 g, 10 mmol) in
Scheme 1.
Keywords: acyl azides; carboxylic acids; sodium azide; triphosgene.
* Corresponding author. Fax: +91-20-5893153; 5893355; e-mail: arasd@dalton.ncl.res.in
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)02377-2

1346
V. K. Gumaste et al. / Tetrahedron Letters 43 (2002) 1345–1346
Table 1. Preparation of acyl azides from carboxylic acids and sodium azide using triphosgene
Entry no.
Substrate
Producta
Yieldb (%)
Mp (°C)c
1
2
3
4
5
6
7
8
Benzoic acid
p-Toluic acid
o-Toluic acid
Benzoyl azide
p-Toluoyl azide
o-Toluoyl azide
p-Nitrobenzoyl azide
o-Chlorobenzoyl azide
Phenoxyacetyl azide
Phenylacetyl azide
Cinnamoyl azide
3,5-Dinitrobenzoyl azide
Nonanoyl azide
81
83
79
55
59
65
85
72
50
96
94
95
Oil
88–90
90–92
p-Nitrobenzoic acid
o-Chlorobenzoic acid
Phenoxyacetic acid
Phenylacetic acid
Cinnamic acid
3,5-Dinitrobenzoic acid
Nonanoic acid
Octanoic acid
68–69 (65–66)9
62–64
Oil
86–88
82–84
9
100–102 (104–105)9
10
11
12
Oil
Oil
Oil
Octanoyl azide
Hexanoyl azide
Hexanoic acid
a All products were fully characterized by spectroscopic data (IR; 1H NMR; MS) and elemental analyses.
b Isolated yield.
c Figures in parentheses show lit. mp.
acetone (20 ml) was added triethylamine (1.01 g, 10
mmol) at 0°C. The reaction mixture was stirred at this
temperature for 15 min and a solution of triphosgene
(0.74 g, 2.5 mmol) in acetone (10 ml) was added
dropwise at 0°C over about 30 min. The reaction
mixture was slowly allowed to warm up to room tem-
perature and stirred for 24 h. The reaction mixture was
filtered to remove insoluble salts and the filtrate was
diluted with an equal volume of petroleum ether. This
solution was passed through a short silica-gel column
and the solvent was removed under reduced pressure at
room temperature to give pure benzoyl azide (0.595 g,
81%).
New York, 1971; pp. 397–405; (b) Lwowski, W. In Azides
Nitrenes; Scriven, E. F. V., Ed.; Academic: Orlando, FL,
1984; pp. 205–246; (c) Moore, H. W.; Goldish, D. M. In
Chem. Halides Pseudo-Halides Azides; Patai, S.; Rappo-
port, Z., Eds.; Wiley: Chichester, UK, 1983; Vol. 1, pp.
321–368.
4. Laszlo, P.; Polla, E. Tetrahedron Lett. 1984, 25, 3701–
3704.
5. (a) Lee, J. G.; Kwak, K. H. Tetrahedron Lett. 1992, 33,
3165–3166; (b) Reddy, P. S.; Yadagiri, P.; Lumin, S.;
Falck, J. R. Synth. Commun. 1988, 18, 545–551.
6. Elmorsy, S. S. Tetrahedron Lett. 1995, 36, 1341–1342.
7. (a) Kobyashi, S.; Kamiyama, K.; Iimori, T.; Ohno, M.
Tetrahedron Lett. 1984, 25, 2557–2560; (b) Canone, P.;
Akssira, M.; Dahouh, A.; Kasmi, H.; Boumzebrra, M.
Heterocycles 1993, 36, 1305–1314.
8. Shao, H.; Colucci, M.; Tong, S.; Zhang, H.; Castelhano,
A. L. Tetrahedron Lett. 1998, 39, 7235–7238.
9. Lago, J. M.; Arrieta, A.; Palomo, C. Synth. Commun.
1983, 13, 289–296.
In summary, we have demonstrated a general method
for the preparation of acyl azides from acids using
triphosgene as an activator.
References
10. Arrieta, A.; Aizpurua, J. M.; Palomo, C. Tetrahedron
Lett. 1984, 25, 3365–3368.
11. Froeyen, P. Phosphorous, Sulfur Silicon Relat. Elem.
1994, 89, 57–61.
1. Cotarca, L.; Delogu, P.; Nardelli, A.; Sunjic, V. Synthesis
1996, 553–576.
2. Krishnaswamy, D.; Bhawal, B. M.; Deshmukh, A. R. A.
12. Kotz, R.; Roestemadji, J.; Mobashery, S. J. Org. Chem.
S. Tetrahedron Lett. 2000, 41, 417–419.
3. (a) Patai, S. The Chemistry of Azido Group; Interscience:
1994, 59, 2913–2914.