Facile generation of vicinal bromoazides from olefins using TMSN3 and TsNBr2 without any catalyst

Article abstract of DOI:10.1016/j.tetlet.2009.06.059

A very rapid and efficient method has been developed for the synthesis of vicinal bromoazides directly from olefin using N,N-dibromo-p-toluenesulfonamide (TsNBr₂) without any catalyst. The reaction is extremely fast which goes into completion instantaneously to produce bromoazides. This procedure is applicable to various olefins such as cinnamates, chalcone, styrenes, and acrylate to give the corresponding 1,2-bromoazide in an excellent yield.

Full text of DOI:10.1016/j.tetlet.2009.06.059

Tetrahedron Letters 50 (2009) 5083–5087
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Tetrahedron Letters
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Facile generation of vicinal bromoazides from olefins using TMSN3
and TsNBr2 without any catalyst
*
Indranirekha Saikia, Prodeep Phukan
Department of Chemistry, Gauhati University, Guwahati 781 014, Assam, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A very rapid and efficient method has been developed for the synthesis of vicinal bromoazides directly
from olefin using N,N-dibromo-p-toluenesulfonamide (TsNBr2) without any catalyst. The reaction is
extremely fast which goes into completion instantaneously to produce bromoazides. This procedure is
applicable to various olefins such as cinnamates, chalcone, styrenes, and acrylate to give the correspond-
ing 1,2-bromoazide in an excellent yield.
Received 3 April 2009
Revised 11 June 2009
Accepted 12 June 2009
Available online 16 June 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Bromoazidation
Trimethylsilyl azide (TMSN3)
N,N-Dibromo-p-toluenesulfonamide
(TsNBr2)
Bromoazide
Olefin
a,b-Unsaturated carbonyl compounds
Acrylates
Styrene
Organic azides are versatile building blocks with a diverse range
which was generated in situ from NBS and NaN3.16 Olah employed
NBS and TMSN3 for the bromoazidation of alkenes in the presence
of Nafion-H in DME/H2O.17 However this procedure was reported
only for 1,2-disubstituted and trisubstituted alkenes and there
was no reaction with terminal alkenes. Recently, Hajra et al
reported a method for 1,2-bromoazidation of alkenes using NBS
and TMSN3 in the presence of Zn(OTf)2 catalyst,18,19 however, me-
tal triflates are highly expensive. Although, this method works well
of applications in organic chemistry,1 with a use as intermediates
for the construction of synthetically and biologically important
compounds such as amines2 and heterocycles.3 In recent past, azi-
do compounds have also been gaining importance as the key inter-
mediates in the emerging field of ‘click chemistry’.4 Haloazidation
is an important organic transformation for simultaneous introduc-
tion of halogen and azide functionality onto an olefin. The resulting
haloazides can be subjected to further synthetic manipulations to
achieve a variety of compounds such as vinyl azide,5 amines,6 azir-
idins,7 and tetrazoles.8 Vicinal iodoazidation is known in the liter-
ature for a long time. Hantsch reported for the first time in 1900 a
strategy for the synthesis of 1,2-iodoazides using silver azide and
iodine in ether.9 1,2-Iodoazides can also be synthesized by treating
ICl/NaN3,10 PhI(OAc)2/Et4NX/TMSN3,11 CAN/NaI/NaN3,12 IPy2BF4/
TMSN3,13 and Oxone/wet Al2O3/KI/NaN314 with alkenes under var-
ious conditions. Poor selectivity and instability of these iodoazides
are the main problems of these methods. Later, Hassner developed
a procedure for vic-bromoazidation of alkene by addition of bro-
mine azide generated from bromine and sodium azide.15 This pro-
cedure requires the use of excess hydrazoic acid to suppress the
formation of dibromo compounds. A similar procedure was also re-
ported by Krief for bromoazidation of alkenes by bromine azide
with terminal and 1,2-disubstituted olefins,
a,b-unsaturated car-
bonyl compounds take much longer time and require higher tem-
perature to achieve a good yield. Moreover, for chalcone, the
reaction does not go into completion even after a long reaction
time at a high temperature with a poor yield. Bromoazidation with
a
,b-unsaturated carboxylic acid derivatives also takes much longer
time even at a higher temperature.19Therefore, the development of
efficient methods for vicinal bromoazidation of alkenes, particu-
larly in the case of a,b-unsaturated alkenes, remains a challenging
task. We are reporting herein a rapid and efficient procedure for
the vicinal bromoazidation of alkenes using N,N-dibromo-p-tolu-
ene sulfonamide (TsNBr2) as bromine source and TMSN3 as azide
source (Scheme 1). This reaction works well with all kinds of al-
kenes including
a,b-unsaturated carbonyl compounds at room
temperature within a very short time, without any catalyst.
N,N-Dibromo-p-toluenesulfonamide is known for a long time
for aminobromination reaction in organic synthesis. Since the
discovery of this reagent by Kharasc,20 it has been utilized for
* Corresponding author. Tel.: +91 94351 11114.
E-mail address: pphukan@yahoo.com (P. Phukan).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.06.059

5084
I. Saikia, P. Phukan / Tetrahedron Letters 50 (2009) 5083–5087
was carried out by adding TMSN3 to the solution of ethylcinnamate
N3
TsNBr2, TMSN3
MeCN, rt
in acetonitrile followed by the addition of TsNBr2. The whole pro-
cess was carried out at room temperature under nitrogen atmo-
sphere. The reaction was studied by using 1.1 equiv of TMSN3
(based on the olefinic substrate) and 1.2 equiv of TsNBr2. We ob-
served that after addition, the olefin disappears instantaneously,
which was confirmed by monitoring the reaction by TLC. The reac-
tion mixture was stirred for another 10 min. After usual work-up
the corresponding bromoazide was obtained in an excellent yield.
The reaction was further studied using different solvents such as
dichloromethane, toluene, carbon tetrachloride, dimethylformam-
ide, and acetone under the same reaction conditions (Table 1). Both
acetonitrile and dichloromethane gave similar results for the azi-
dobromination reaction. However, use of other solvents such as
toluene, carbon tetrachloride, DMF, and acetone was not fruitful
(Table 1).
The reagent is much faster than NBS for bromoazidation reac-
tion. Secondly, for NBS-assisted bromoazidation reaction, it is nec-
essary to add a suitable catalyst to promote the reaction.17,18 But,
in this case, reaction goes into completion without any catalyst.
This process was extended to a variety of olefins in acetonitrile
as solvent. The results are summarized in Table 2. Initially, we
examined the reaction for different cinnamic esters. It can be seen
from Table 2 that various cinnamic esters bearing functional
groups such as –CH3, –OMe, –Cl, and –F reacted successfully to give
the corresponding 1,2-bromoazide in high yields irrespective of the
substituent position on the aromatic ring.24 Cinnamic esters having
both electron-withdrawing and electron-donating groups could
also be converted to the corresponding products in high yields.
The reaction is regioselective, however, moderate stereoselectivity
R'
R'
R
R
Br
R = Aryl, H
R' = Aryl, alkyl, COR, COOR
Scheme 1.
Table 1
Synthesis of bromoazides in different solvents
Entry
Solvent
Yield (%)
1
2
3
4
5
6
CH3CN
CH2Cl2
Toluene
CCl4
DMF
Acetone
76
76
58
61
58
39
Reaction conditions: olefin (1 mmol), TMSN3 (1.1 mmol), TsNBr2 (1.2 mmol), sol-
vent (2 mL), rt, 10 min.
aminobromination of a variety of olefinic substrates.21 Recently,
we have also developed a method for the synthesis of bromohy-
drins and alkoxy bromides using TsNBr2.22 The brominating agent
TsNBr2 employed for this purpose was prepared from Chloramine-
T by following literature procedure.23
To begin with, a study on the bromoazidation reaction was car-
ried out with ethyl cinnamate as a model substrate. The reaction
Table 2
a
Bromoazidation of various alkenes with TsNBr2 and TMSN3
Entry
Alkene (a)
Product (b)
Yieldb
76
anti/syn ratioc
N3
O
O
1
70:30
OC2H5
OC2H5
Br
O
N3
O
OC2H5
OC2H5
2
78
73:27
Br
H3C
H3C
OMe
N3
O
OMe
O
3
4
5
85
86
83
64:36
56:44
nd
OMe
O
OMe
O
Br
Cl
N3
Cl
OC2H5
OC2H5
Br
Br
Cl
Cl
F
O
N3
O
OC2H5
OC2H5
F

I. Saikia, P. Phukan / Tetrahedron Letters 50 (2009) 5083–5087
5085
Table 2 (continued)
Entry
Alkene (a)
Product (b)
Yieldb
84
anti/syn ratioc
O
N3
O
6
7
nd
nd
OC2H5
OC2H5
Br
Br
Br
O
N3
O
OC2H5
OC2H5
85
Br
Cl
F
Cl
F
O
N3
O
OMe
OMe
8
9
85
83
69:31
80:20
Br
Br
Br
O
N3
O
Cl
Cl
OMe
OMe
Br
MeO
MeO
OMe N3
O
OMe
O
10
70
>99.1
OMe
OMe
Br
OMe
OMe
MeO
MeO
N3
O
O
11
12
13
52
85
69
nd
OC2H5
OC2H5
O
O
Br
N3
>99:1
>99.1
—
Br
O
O
N3
Br
N3
14
15
82
77
Br
Br
N3
—
(continued on next page)

5086
I. Saikia, P. Phukan / Tetrahedron Letters 50 (2009) 5083–5087
Table 2 (continued)
Entry
Alkene (a)
Product (b)
Yieldb
78
anti/syn ratioc
O
N3
O
16
17
—
OC2H5
OC2H5
Br
N3
Br
49
—
Br
N3
18
48
50
—
—
N3
O
O
19
Br
a
Reaction condition: olefin (1 mmol), TMSN3 (1.1 mmol), TsNBr2 (1.2 mmol), MeCN (2 mL), rt, 10 min.
Isolated yield after chromatographic purification.
anti/syn ratio was determined from NMR spectral data; nd: not determined.
b
c
was obtained for most of the cases. Bromoazides produced from
In conclusion, an efficient protocol for vicinal bromoazidation of
olefins has been established by using N,N-dibromo-p-toluenesul-
fonamide in acetonitrile at room temperature without the use of
any catalyst. The procedure is extremely fast, easy to perform at
room temperature, and applicable to various olefins such as cinna-
mates, chalcone, styrenes, and acrylate to give corresponding 1,2-
bromoazide in high yields. However, the reaction is not very effec-
tive in the case of aliphatic alkenes such as cyclohexene and 1-oc-
tene. The study in this area is in progress.
cinnamic esters have anti/syn ratio of about 3:1 which was deter-
mined from the 1H NMR analysis. Interestingly, the reaction is
highly stereoselective in case of 20,40,60-trimethoxycinnamate
yielding only the erythro-b-azido-a-bromo isomer as evident by
the analysis of 1H NMR data. The same result of exclusive
anti-selectivity was also observed in the case of stilbene and chal-
cone (Table 1, entry 9). After being successful in the case of cin-
namic esters, stilbene, and chalcone, we extended the procedure
to styrenes and ethyl acrylate, which produced the corresponding
bromoazide in high yields. The procedure was further examined
in the case of 3-(2-furyl) acrylate, cyclohexene, allyloxybenzene,
and 1-octene. But the reaction was not successful with these sub-
strates. Lower yield of the corresponding product was observed in
all the cases.
Acknowledgment
Financial support from DST (Grant No. SR/S1/RFPC-07/2006) is
gratefully acknowledged.
A probable mechanistic pathway to explain the regio- and ste-
reoselectivity of the bromohydrins and bromoethers is depicted
in Scheme 2. A three-membered cyclic bromonium ion intermedi-
ate 20 is formed at the initial stage of the reaction due to electro-
philic addition of the Br+ ion (generated from TsNBr2) onto the
olefin.25 The regioselectivity can be explained by considering the
References and notes
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O
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Scheme 2. Probable mechanistic pathway.

I. Saikia, P. Phukan / Tetrahedron Letters 50 (2009) 5083–5087
5087
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15 minutes. The reaction mixture was taken up in ethyl acetate, dried over
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2106.4, 1743, 1265.6, 1022, 740.4; 1H NMR (CDCl3, 400 MHz) d: 7.46–7.32 (m,
5H), 5.21 (d, J = 6.5 Hz, 1H), 4.39 (d, J = 9.5 Hz, 1H), 4.34–4.29 (m, 2H), 1.34 (t,
J = 3.6, 3H); 13C NMR (CDCl3, 100 MHz) d: 14.1, 49.5, 52.6. 62.5, 67.2, 128.3, 128.3,
128.8, 129.0, 129.5. GC–MS (M/Z%): 269 (M+ꢀ28, N2 elimination, 62), 271 (62),
195 (62), 197 (59), 189 (33), 162 (26), 143 (59), 116 (87), 90 (100), 63 (44), 29
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) m
400 MHz) d: 7.39–7.23 (m, 4H), 5.12 (d, J = 9.2 Hz, 1H), 4.367 (d, J = 9.2 Hz, 1H),
3.83 (s, 3H); 13C NMR (CDCl3, 100 MHz) d:168.0, 138.8, 130.3, 129.8, 128.7, 126.7,
67.3, 53.4, 53.3, 48.2; GC–MS (M/Z%): 289 (M+ꢀ28, N2 elimination, 37), 291 (44),
231 (67), 229 (56), 204 (11), 182 (10), 153 (100), 139(16), 123 (51), 116(34), 89
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) m
d: 1.331 (t, J = 7.2 Hz, 3H), 3.93–3.88 (q, J = 8.4 Hz, 2H), 4.28 (t, J = 7.6 Hz, 1H). 13C
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