A simple one-pot method for the preparation of allyl azides from allyl alcohols using triphosgene: Synthesis of N1-cinnamyl azetidin-2-ones

Article abstract of DOI:10.1055/s-2004-820046

A simple and efficient one-pot method for the preparation of allyl azides from allyl alcohols using triphosgene and sodium azide is described. An application of cinnamyl azide for the synthesis of various N1 -cinnamyl azetidin-2-ones is also described.

Full text of DOI:10.1055/s-2004-820046

LETTER
979
A Simple One-Pot Method for the Preparation of Allyl Azides from Allyl
Alcohols Using Triphosgene: Synthesis of N1-Cinnamyl Azetidin-2-ones
Synthesis of
N
1-Ci
.
nnamyl
A
zet
J
idin-2-on
a
e
s
yanthi, V. K. Gumaste, A. R. A. S. Deshmukh*
Division of Organic Chemistry (Synthesis), National Chemical Laboratory, Pune – 411 008, India
Fax +91(20)25893153; fax 25893355; E-mail: arasd@dalton.ncl.res.in
Received 9 January 2004
Dedicated to Dr. S. Rajappa on the occasion of his 70th birthday.
Abstract: A simple and efficient one-pot method for the prepara-
tion of allyl azides from allyl alcohols using triphosgene and sodi-
um azide is described. An application of cinnamyl azide for the
synthesis of various N1-cinnamyl azetidin-2-ones is also described.
Key words: allyl azides, allyl alcohols, azetidin-2-ones, triphos-
gene
Recently we have shown the versatility of triphosgene
[bis(trichloromethyl)carbonate]1 as an acid activator in
the construction of b-lactam ring via ketene-imine cy-
cloaddition using Staudinger reaction.2 We have also used
this reagent for the preparation of various azidoformates3
Scheme 1
and acyl azides4. In this communication we wish to report
a simple and efficient one-pot method for the preparation
cinnamyl azidoformate was found to be a minor product
(20% by GLC and 1H NMR).11
of allyl azides directly from allyl alcohols using triphos-
gene and sodium azide. Although, allyl azides are impor-
tant synthetic intermediates5 and a source for synthetically
useful allyl amines,6 there are very few methods available
for their preparation from allyl acetates,8 allyl halides9 and
allysilanes.10 There are also some reports on one-pot con-
version of allyl alcohols to allyl azides.7
Cinnamyl azide (1) could be obtained in excellent isolated
yield (80%) and very high purity (>98%, GLC) by a little
modification in the experimental procedure. Accordingly
a solution of cinnamyl alcohol and triethylamine in ace-
tone was added to a stirred solution of triphosgene in ace-
tone at 0 °C followed by the addition of sodium azide in
one portion. The reaction mixture was stirred at room tem-
perature for 12 hours and the usual work-up gave excel-
lent yield of cinnamyl azide of high purity.12
In a recent communication we have shown that the reac-
tion of triphosgene with the aliphatic alcohols in the pres-
ence of sodium azide and triethylamine gives
azidoformates in excellent yields.3 However, under simi-
lar reaction conditions, when triphosgene was added
slowly to a mixture of cinnamyl alcohol, triethylamine
and sodium azide in acetone at 0 °C, cinnamyl azide (1)
was obtained as a major product (80%) while the expected
The formation of 1 could be through the allyl carbocation
generated from trichloromethyl allyl carbonate or allyl
chloroformate with the evolution of carbon dioxide fol-
lowed by nucleophilic addition of azide ion (Scheme 1).
Scheme 2
SYNLETT 2004, No. 6, pp 0979–0982
0
6.
0
5.
2
0
0
4
Advanced online publication: 25.03.2004
DOI: 10.1055/s-2004-820046; Art ID: G01404ST
© Georg Thieme Verlag Stuttgart · New York

980
A. Jayanthi et al.
LETTER
Table 1 Preparation of Allyl Azides Using Triphosgene and Sodium Azide
Entry
Substrate
Product
Yield (%)a
1
2
80
90
3
66
4
5
60
91
6
7
8
66b
50c
46
8
63
64
10
a Isolated yields.
b Mixture of geranyl azide (66%, E/Z, 60:40) and linalyl azide (10%).
c Mixture of primary azide and tertiary azide (75:25).
This is evident from the fact that the reaction of geraniol and 4). Benzyl alcohol also gave benzyl azide in very
with triphosgene in the presence of sodium azide under good yield when reacted with triphosgene and sodium
similar reaction conditions gave E/Z mixture (60:40) of azide (Table 1, entry 10). The low yields of azides in case
geranyl azides (66%) along with small amount of linalyl of lower allyl alcohols may be due to low reactivity of al-
1
azide (10%), which was confirmed from the H NMR cohols and the volatile nature of the allyl azides formed.
spectrum of the reaction product (Scheme 2).
In fact we could not isolate allyl azides from lower allyl
alcohols such crotyl, allyl and methallyl alcohols.14
Attempts to separate linalyl azide and geranyl azide from
the mixture were unsuccessful. Prenol also gave insepara- After developing an efficient method for allyl azides we
ble mixture of primary and tertiary allyl azides (75:25) in were interested in their application for synthetic utility. As
low isolated yield (50%).
a part of our on going research program on the synthesis
of polycyclic b-lactams15 via radical cyclization reaction
we were in need of N1-allyl substituted b-lactams. We
have successfully utilized allyl azides for the synthesis of
N1-allyl-b-lactam substrates (Scheme 3) required for in-
tramolecular radical cyclization study.
Several allyl azides were prepared by this method in good
to moderate yields (Table 1).13 1-Phenyl-3-methyl prop-
2-en-1-ol and 3-phenyl-1-methyl prop-2-en-1-ol gave
same, 3-phenyl-1-methyl prop-2-en-1-azide, product
through a common stable carbocation (Table 1, entries 3
Scheme 3
Synlett 2004, No. 6, 979–982 © Thieme Stuttgart · New York

LETTER
Synthesis of N1-Cinnamyl Azetidin-2-ones
981
Table 2 Synthesis of N-Cinnamyl Azetidin-2-ones (4a–g)
Entry
Compound
R1
R2
Yield (%)a,b
Mp (°C)
1
2
3
4
5
4a
4b
4c
4d
4e
Ph
OCH2Ph
OPh
74
84
84
72
76
140–141
160–161
90–92
Ph
Ph
OMe
2-BrPh
OCH2Ph
OCH2Ph
120–122
142–143c
6
4f
4-MeOPh
4-MeOPh
OMe
61
78
122–123
120–121
7
4g
OCH2Ph
a Isolated yields.
b All the compounds gave satisfactory elemental analyses and spectral data.
c Mp of one of the diastereomers isolated from (1:1) diastereomeric mixture.
(4) Gumaste, V. K.; Bhawal, B. M.; Deshmukh, A. R. A. S.
Tetrahedron Lett. 2002, 43, 1345.
The iminophosphorane 2, obtained from cinnamyl azide
and triphenylphosphine, was treated with aldehyde to get
aza-Wittig product 3, which was found to be unstable and
used as such without purification. The cycloaddition reac-
tion of imine 3 with ketene, generated from acid chloride
and triethylamine, gave cis-N-cinnamyl-b-lactams (4a–g)
in good yields (Table 2).16 The chiral iodoaldehyde de-
rived from D-glucose17 was also used for the preparation
of N-cinnamyl imine 3e, which on further reaction with
ketene gave 1:1 diastereomeric mixture of cis-b-lactams
4e in very good yield (Table 2, entry 5). Both the diaste-
reomers could be separated by careful column chromatog-
raphy. Further work on the application of other allyl
azides for the synthesis of N-allyl azetidin-2-ones is in
progress.
(5) (a) Patai, S. The Chemistry of Azido Group; Interscience:
New York, 1971, 83–85. (b) Molina, P.; Alajarin, M.;
Lopez-Leonardo, C. Tetrahedron Lett. 1991, 32, 4041.
(6) Cheikh, R. B.; Chaabouni, R.; Laurent, A.; Mison, P.; Nafti,
A. Synthesis 1983, 685.
(7) (a) Crandall, J. K.; Michaely, W. J. J. Org. Chem. 1984, 49,
4244. (b) Kanai, T.; Kanagawa, Y.; Ishii, Y. J. Org. Chem.
1990, 55, 3274. (c) Sampath Kumar, H. M.; Subba Reddy,
B. V.; Anjaneyulu, S.; Yadav, J. S. Tetrahedron Lett. 1998,
39, 7385. (d) Malkov, A. V.; Spoor, P.; Vinader, V.;
Kocovsky, P. J. Org. Chem. 1999, 64, 5308. (e) Reddy, G.
V. S.; Venkatrao, G.; Subramanyam, R. V. K.; Iyengar, D. S.
Synth. Commun. 2000, 30, 2233. (f) Chandrasekhar, S.;
Raza, A.; Takhi, M. Tetrahedron: Asymmetry 2002, 13, 423.
(8) (a) Murahashi, S. I.; Taniguchi, Y.; Imada, Y.; Tanigawa, Y.
J. Org. Chem. 1989, 54, 3292. (b) Murahashi, S. I.;
Tanigawa, Y.; Imada, Y.; Taniguchi, Y. Tetrahedron Lett.
1986, 27, 227. (c) Safi, M.; Fahrang, R.; Sinou, D.
Tetrahedron Lett. 1990, 31, 527.
In summary, we have demonstrated a one-pot method for
the preparation of allyl azides from allyl alcohols using
triphosgene and sodium azide and shown the utility of cin-
namyl azide for the synthesis of N-cinnamyl-b-lactams.
(9) (a) Priebe, H. Acta Chem. Scand., Ser. B 1984, 38, 895.
(b) Kozaburo, N.; Hiroshi, K. Chem. Lett. 1982, 1477.
(10) (a) Arimoto, M.; Yamaguchi, H.; Fujita, E.; Nagao, Y.;
Ochiai, M. Chem. Pharm. Bull. 1989, 37, 3221.
Acknowledgment
(b) Arimoto, M.; Yamaguchi, H.; Fujita, E.; Ochiai, M.;
Nagao, Y. Tetrahedron Lett. 1987, 28, 6289.
Authors thank DST, New Delhi for financial support and AJ thanks
CSIR, New Delhi for research fellowship.
(11) Spectral data for cinnamyl azidoformate: colorless oil. IR
(CHCl3): 2175, 2135, 1730, 1500, 1448, 1236, 966 cm–1. 1H
NMR (300 MHz, CDCl3): d = 4.88 (d, J = 6.0 Hz, 2 H),
6.25–6.35 (m, 1 H), 6.73 (d, J = 16.0 Hz, 1 H), 7.20–7.45
(m, 5 H).
(12) Cinnamyl azide (1) and other allyl azides were found to be
stable at r.t. but for safety reason they were stored in the
refrigerator. [CAUTION: We did not observe any untoward
incidence while working with allyl azides. However, the use
of hood and safety shield is recommended, as azides are
known for their explosive property].
References
(1) (a) Cotarca, L.; Delogu, P.; Nardelli, A.; Sunjic, V. Synthesis
1996, 553. (b) Heintzelman, G. R.; Fang, W. K.; Keen, S. P.;
Wallace, G. A.; Weinreb, S. M. J. Am. Chem. Soc. 2001,
123, 8851. (c) White, J. D.; Hansen, J. D. J. Am. Chem. Soc.
2002, 124, 4950.
(2) (a) Krishnaswamy, D.; Bhawal, B. M.; Deshmukh, A. R. A.
S. Tetrahedron Lett. 2000, 41, 417. (b) Krishnaswamy, D.;
Govande, V. V.; Gumaste, V. K.; Bhawal, B. M.;
Deshmukh, A. R. A. S. Tetrahedron 2002, 58, 2215.
(3) Patil, R. T.; Ghazala, P.; Gumaste, V. K.; Bhawal, B. M.;
Deshmukh, A. R. A. S. Synlett 2002, 1455.
(13) Typical Experimental Procedure for the Preparation of
Cinnamyl Azide (1): To a stirred solution of triphosgene
(1.48 g, 5 mmol) in acetone (20 mL) was added a solution of
cinnamyl alcohol (1.34 g, 10 mmol) and Et3N (1.51 g, 15
Synlett 2004, No. 6, 979–982 © Thieme Stuttgart · New York

982
A. Jayanthi et al.
LETTER
mmol) at 0 °C. The reaction mixture was stirred for 20 min
and then at r.t. for 3 h. It was cooled to 0 °C and sodium azide
(1.30 g, 20 mmol) was added in one portion. It was stirred at
this temperature for 1 h and kept at r.t. for 12 h. To the
reaction mixture H2O (20 mL) was added and extracted with
Et2O (3 × 20 mL). The organic layer was washed with brine
(20 mL) and dried over anhyd Na2SO4. The solvent was
removed under reduced pressure at r.t. to get pure cinnamyl
azide(1) as yellow oil (1.28 g, 80%). [CAUTION: We did
not observe any untoward incidence while working with
allyl azides. However, the use of hood and safety shield is
recommended, as azides are known for their explosive
property.] IR (CHCl3): 2100, 1492, 1448, 1350, 1236, 968
cm–1. 1H NMR (300 MHz, CDCl3): d = 3.96 (d, J = 6.0 Hz,
2 H), 6.15–6.35 (m, 1 H), 6.67 (d, J = 17.0 Hz, 1 H), 7.10–
7.55 (m, 5 H). MS: m/z (%) = 159 (15) [M+], 130 (57), 117
(100), 104 (74).
reaction mixture was refluxed for 6 h. The reaction mixture
was cooled to 0 °C and benzaldehyde (0.212 g, 2 mmol) was
added to the reaction mixture. It was stirred at r.t. for 12 h.
Solvent was removed under reduced pressure and the residue
containing imine 3a and triphenylphosphine oxide was
dissolved in dry CH2Cl2 (20 mL) and directly used for the
next reaction without isolation of the imine 3a since it was
found to be unstable.
To the above solution of imine in CH2Cl2, Et3N (0.91 g, 9
mmol) was added and the solution was cooled to –15 °C. A
solution of benzyloxyacetyl chloride in CH2Cl2 (10 mL) was
added slowly with stirring in about 30 min and the reaction
mixture was allowed to warm up to r.t. and stirred for 18 h.
It was washed with H2O (20 mL), sat. NaHCO3 solution (20
mL), brine (10 mL) and dried over anhyd Na2SO4. Solvent
was removed under reduced pressure and the crude product
was purified by column chromatography to get white solid
b-lactam 4a in 74% yield. White solid, mp 140–141 °C. IR
(CHCl3): 1751 cm–1. 1H NMR (200 MHz, CDCl3): d = 3.60
(dd, J = 7.8 and 15.1 Hz, 1 H), 4.18 (d, J = 11.2 Hz, 1 H),
4.25 (d, J = 11.2 Hz, 1 H), 4.34–4.41 (m, 1 H), 4.79 (d,
J = 4.4 Hz, 1 H), 4.92 (d, J = 4.4 Hz, 1 H), 5.96–6.11 (m, 1
(14) In these cases, N,N-dimethyl carbamoyl azide was obtained
as a by-product, which was arising from the reaction of Et3N,
triphosgene and sodium azide with the loss of ethyl group.
This reaction will be studied in detail and results will be
communicated in future.
(15) (a) Joshi, S. N.; Puranik, V. G.; Deshmukh, A. R. A. S.;
Bhawal, B. M. Tetrahedron: Asymmetry 2001, 12, 3073.
(b) Joshi, S. N.; Phalgune, U. D.; Bhawal, B. M.; Deshmukh,
A. R. A. S. Tetrahedron Lett. 2003, 44, 1827.
(16) Typical Experimental Procedure for the Preparation of
N-Cinnamyl Azetidin-2-one (4a): To a solution of
cinnamyl azide (0.318 g, 2 mmol) in toluene (20 mL) was
added triphenylphosphine (0.524 g, 2 mmol) and the
H), 6.39 (d, J = 15.6 Hz, 1 H). 6.94–7.40 (m, 15 H). 13
C
NMR (125 MHz, CDCl3): d = 42.1, 61.6, 72.1, 83.6, 122.1,
126.3, 127.7, 127.8, 128.0, 128.1, 128.3, 128.4, 128.5,
134.2, 136.1, 136.3, 166.7. MS: m/z = 369 (M+). Anal. Calcd
for C25H23NO2: C, 81.27; H, 6.27; N, 3.79. Found: C, 81.44;
H, 6.33; N, 3.67.
(17) Garegg, P. J.; Samuelsson, B. J. Chem. Soc., Perkin Trans. 1
1980, 2866.
Synlett 2004, No. 6, 979–982 © Thieme Stuttgart · New York