Synthesis of sulfonyl azides

Article abstract of DOI:10.1055/s-2008-1072568

1-(Alkylsulfonyl)- and 1-(arylsulfonyl)benzotriazoles react with sodium azide in acetonitrile to give the corresponding alkanesulfonyl and arenesulfonyl azides. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1072568

PAPER
1201
Synthesis of Sulfonyl Azides
S
ynthesis of Sulfo
l
nyl
A
zi
a
de
s
n Katritzky,*a Khalid Widyan,a,b Kapil Gyandaa
a
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA
Fax +1(352)3929199; E-mail: katritzky@chem.ufl.edu
Department of Chemistry, Tafila Technical University, Tafila 66110, Jordan
b
Received 1 August 2007; revised 4 January 2008
vide efficient N-sulfonylation of amines and C-sulfonyla-
tion of nitriles, heteroaromatics, sulfones and esters to
produce a-cyanoalkyl sulfones, sulfonylheteroaromatics,
a-sulfonylalkyl sulfones and esters of a-sulfonyl acids, re-
spectively.17 They are also useful in the synthesis of
N-acylbenzotriazole from the corresponding carboxylic
acid.18–20 Herein we report the application of 1-sulfonyl-
benzotriazoles to the preparation of sulfonyl azides.
Abstract: 1-(Alkylsulfonyl)- and 1-(arylsulfonyl)benzotriazoles
react with sodium azide in acetonitrile to give the corresponding
alkanesulfonyl and arenesulfonyl azides.
Key words: synthesis, 1-sulfonylbenzotriazoles, sulfonyl azides,
sodium azide, Grignard reagent
Sulfonyl azides (RSO2N3) are valuable reagents for diazo
transfer to the a-methylene position of carbonyl com-
pounds such as b-oxo esters and oxo sulfones.1,2 Charette
and co-workers reported trifluoromethanesulfonyl azide
(triflyl azide, 1), a highly electrophilic diazo-transfer re-
agent, gives good results with activated acetic acid esters
and ketones (Figure 1).3,4 3-Pyridinesulfonyl azide (2) ap-
pears to be more efficient for radical azidating than 4-
(methoxycarbonyl)benzenesulfonyl azide and 3- and 4-
carboxybenzenesulfonyl azides.5,6 Sulfonyl azides [espe-
cially 2,4,6-triisopropylbenzenesulfonyl azide (3)] have
been used in the a-azidation of amide enolates and ester
enolates in the synthesis of a-amino acid derivatives.7
O
(RSO2)2O
R
S
NHNH2
NaNO2
O
NaN3
R
(iii)
(ii)
O
S
O
O
O
R
NaN3
(i)
NaN3
(iv)
S
S
N3
R
S
X
R
O
O
O
O
X = Cl, F
Scheme 1 Survey of various syntheses of sulfonyl azides
1-Sulfonylbenzotriazoles 4 are accessible from aryl- and
alkyllithium or Grignard reagents by reaction with sulfur
dioxide and 1-chlorobenzotriazole (Table 1).16
Treatment of 4 with sodium azide (1.5 equiv) in acetoni-
trile for 3–10 hours under reflux gave the sulfonyl azides
5 in synthetically useful yields (Table 2). This approach
affords a variety of novel alkanesulfonyl and heteroarene-
sulfonyl azides (compounds 5b, 5e, 5f, 5h, 5i and 5k–n)
and improved the yields for compounds 5a and 5g (the
yield for compound 5a is not reported in the literature).
An advantage of our procedure is the use of 1-sulfonyl-
benzotriazoles which are crystalline compounds, easily
accessible, and stable to storage over years. Furthermore,
this approach avoids the use of hydrazides and NO+ equiv-
alents, and multistep syntheses.
O
S
O
S
O
S
N3
N3
CF3
N3
N
O
O
O
1
3
2
Figure 1
The reaction of sodium azide with a sulfonyl halide is the
most direct synthetic approach to sulfonyl azides
(Scheme 1).6,8–10 Less common approaches include reac-
tions of sulfonyl anhydrides and a-disulfones with sodium
azide.11–13 Diazotization of sulfonyl hydrazides with NO+
has also been employed but requires the availability of the
hydrazides.14,15 All these procedures may suffer from the
unavailability of starting materials or their difficulty in
preparation, thus a new and convenient method for the
preparation of sulfonyl azides would be advantageous.
The present procedure requires only simple manipulations
and low-priced reagents; thus, it should be appropriate for
providing highly demanded derivatives. The present work
provides additional evidence for the good leaving ability
of a benzotriazole group.
In conclusion, a new method for the synthesis of a variety
of alkanesulfonyl, arenesulfonyl and heteroarenesulfonyl
azides has been developed using 1-sulfonylbenzotri-
azoles. This approach broadens the range of available sul-
fonyl azides, which are compounds of major synthetic
importance.
Recently, we developed a general and facile method for
the preparation of 1-sulfonylbenzotriazoles 4 as a practi-
cal alternative to the frequently labile and often difficult to
access sulfonyl halides.16 1-Sulfonylbenzotriazoles 4 pro-
SYNTHESIS 2008, No. 8, pp 1201–1204
x
x
.
x
x
.2
0
0
8
Advanced online publication: 27.03.2008
DOI: 10.1055/s-2008-1072568; Art ID: M05707SS
© Georg Thieme Verlag Stuttgart · New York

1202
A. Katritzky et al.
PAPER
Table 1 Preparation of 1-(Alkylsulfonyl)- and 1-(Arylsulfonyl)benzotriazoles 4
O
N
BtCl, Et3N
N
SO2
+
R
M
R
S
O
4
N
4
R
M
Yielda (%)
Mp (°C)
Lit. mp (°C)
Ref.
a
b
c
d
e
f
n-butyl
Li
68
74
90
80
22
85
73
82
75
50
60
11
45
35
oil
oil
16
16
16
16
16
16
16
16
17
16
17
–
cyclohexyl
4-tolyl
MgCl
MgBr
Li
118–119
131–132
142–144
131–133
108–109
130–132
146–149
147–148
128–130
96–97
117–119
133–134
143–144
131–132
107–109
132–135
147–150
147–148
128–129
147–148
2-thienyl
1-methyl-1H-indol-2-yl
2-furyl
Li
Li
g
h
i
2-pyridyl
Li
1-methyl-1H-imidazol-2-yl
2-benzofuryl
Li
Li
j
3-pyridyl
Li
k
l
5-ethyl-2-furyl
2-thiazolyl
Li
b
Li
114–116
104–106
114–116
–
b
m
n
5-methyl-2-thienyl
5-methyl-2-furyl
Li
–
–
b
Li
–
–
a Isolated yields.
b Novel compound.
Table 2 Preparation of Alkanesulfonyl and Arenesulfonyl Azides 5
O
S
N
N
O
S
NaN3
N
R
N3
R
O
MeCN
O
4
5
This work
Time (h)
Literature
Methodb
5
R
Yielda (%) Mp (°C)
Yield (%)
Mp (°C)
oil
Ref.
c
a
b
c
d
e
f
n-butyl
3
6
86
55
88
70
30
68
90
45
23
45
40
oil
(i)
–
–
–
21
–
d
cyclohexyl
4-tolyl
oil
–
4
oil
(iii)
(i)
–
96
85
–
22–25
31–33
14
22
–
2-thienyl
4
30–32
oil
d
1-methyl-1H-indol-2-yl
2-furyl
6
–
d
6
oil
–
–
–
–
g
h
i
2-pyridyl
3
oil
(i)
–
66
–
–
23
–
d
1-methyl-1H-imidazol-2-yl
2-benzofuryl
7
39–41
58–60
oil
–
d
7
–
–
–
–
j
3-pyridyl
6
(i)
–
80
–
oil
24
–
d
k
5-ethyl-2-furyl
10
oil
–
d
l
2-thiazolyl
8
10
10
25
30
40
oil
oil
oil
–
–
–
–
–
–
–
–
–
–
d
m
n
5-methyl-2-thienyl
5-methyl-2-furyl
–
d
–
a Isolated yields.
b See Scheme 1.
c Yield not reported.
d Novel compound.
Synthesis 2008, No. 8, 1201–1204 © Thieme Stuttgart · New York

PAPER
Synthesis of Sulfonyl Azides
1203
1
Melting points are uncorrected. H (300 MHz) and 13C (75 MHz)
NMR spectra were recorded on a Varian 300 MHz spectrometer in
CDCl3 solution with TMS as internal standard. THF was distilled
from sodium benzophenone ketyl prior to use. All reactions were
performed under a nitrogen atmosphere and in oven-dried glass-
ware. Column chromatography was performed on silica gel, 200–
425 mesh. HRMS were recorded with a Thermoscientific DSQ
mass spectrometer in CI mode.
solved in Et2O (100 mL), then washed with dilute aq Na2CO3
(2 × 50 mL) and H2O (2 × 50 mL). The organic layer was dried
(MgSO4) and filtered. The solvent was evaporated under reduced
pressure and the residue was purified by column chromatography
(hexane–Et2O, 2:1) to give the sulfonyl azide.
1-Butanesulfonyl Azide (5a)21
Pale yellow oil; yield: 86%.
1H NMR (300 MHz, CDCl3): d = 0.99 (t, J = 7.3 Hz, 3 H), 1.45–
1.55 (m, 2 H), 1.85–1.97 (m, 2 H), 3.28–3.36 (m, 2 H).
1-Sulfonylbenzotriazoles 4a–k were prepared according to previ-
ously published procedures.16,17
13C NMR (75 MHz, CDCl3): d = 13.4, 21.2, 25.2, 55.7.
1-Sulfonylbenzotriazoles 4l–n; General Procedure
SO2 was bubbled into a soln of an organometallic reagent (14
mmol) in anhyd THF (50 mL) at –78 °C under N2 atmosphere until
a sample of the soln no longer gave a basic pH test. 1-Chlorobenzo-
triazole (2.14 g, 14 mmol) was added in one portion at r.t., and the
mixture was stirred for 2 h. Et3N (1.84 mL, 14 mmol) was added,
followed by stirring at r.t. for 16 h. H2O (ca. 150 mL) was added to
the reaction mixture and the product was extracted with EtOAc
(3 × 100 mL). The combined organic layers were washed with H2O
(2 × 50 mL) and brine (2 × 50 mL), then dried (MgSO4) and fil-
tered. After concentration, the residue was purified either by recrys-
tallization or by column chromatography over silica gel (200–425
mesh).
Cyclohexanesulfonyl Azide (5b)
Colorless oil; yield: 55%.
1H NMR (300 MHz, CDCl3): d = 1.19–1.43 (m, 3 H), 1.52–1.86 (m,
3 H), 1.87–2.01 (m, 2 H), 2.21–2.39 (m, 2 H), 3.16–3.28 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 24.7, 24.9, 26.2, 65.6.
HRMS: m/z [M + H]+ calcd for C6H12N3O2S: 190.0645; found:
190.0661.
4-Toluenesulfonyl Azide (5c)14
Colorless oil; yield: 88%.
1H NMR (300 MHz, CDCl3): d = 2.49 (s, 3 H), 7.41 (d, J = 8.1 Hz,
2 H), 7.85 (d, J = 8.4 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 21.7, 127.5, 130.3, 135.4, 146.2.
1-(2-Thiazolylsulfonyl)-1H-1,2,3-benzotriazole (4l)
White solid; yield: 11%; mp 114–116 °C.
1H NMR (300 MHz, CDCl3): d = 7.55 (t, J = 7.5 Hz, 1 H), 7.74 (t,
J = 7.5 Hz, 1 H), 7.82 (d, J = 2.9 Hz, 1 H), 7.96 (d, J = 2.9 Hz, 1 H),
8.13 (d, J = 8.2 Hz, 1 H), 8.20 (d, J = 8.2 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 103.3, 112.5, 120.7, 126.4, 128.0,
130.9, 131.9, 145.6.
2-Thiophenesulfonyl Azide (5d)
Pale yellow microcrystals; yield: 70%; mp 30–32 °C (Lit.22 31–33
°C).
1H NMR (300 MHz, CDCl3): d = 7.20–7.24 (m, 1 H), 7.78–7.86 (m,
2 H).
13C NMR (75 MHz, CDCl3): d = 128.0, 134.7, 135.1, 138.1.
Anal. Calcd for C9H6N4O2S2: C, 40.59; H, 2.27; N, 21.04. Found:
C, 40.92; H, 2.08; N, 20.77.
1-Methyl-1H-indole-2-sulfonyl Azide (5e)
Pale yellow oil; yield: 30%.
1-(5-Methyl-2-thienylsulfonyl)-1H-1,2,3-benzotriazole (4m)
White solid; yield: 45%; mp 104–106 °C.
1H NMR (300 MHz, CDCl3): d = 3.99 (s, 3 H), 7.21–7.30 (m, 1 H),
7.40–7.54 (m, 3 H), 7.76 (d, J = 8.1 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 31.3, 110.5, 112.2, 121.7, 123.2,
124.5, 126.9, 130.8, 139.7.
1H NMR (300 MHz, CDCl3): d = 2.50 (s, 3 H), 6.79 (d, J = 3.2 Hz,
1 H), 7.50 (t, J = 8.1 Hz, 1 H), 7.68 (t, J = 8.0 Hz, 1 H), 7.77 (d,
J = 3.8 Hz, 1 H), 8.06–8.13 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 15.8, 112.0, 120.5, 125.9, 126.8,
130.2, 131.2, 132.8, 136.4, 145.4, 152.9.
HRMS: m/z [M]+ calcd for C9H8N4O2S: 236.0362; found: 236.0357.
Anal. Calcd for C11H9N3O2S2: C, 47.30; H, 3.25; N, 15.04. Found:
C, 47.67; H, 3.16; N, 14.87.
2-Furansulfonyl Azide (5f)
Pale yellow oil; yield: 68%.
1H NMR (300 MHz, CDCl3): d = 6.62–6.64 (m, 1 H), 7.26–7.28 (m,
1 H), 7.70 (s, 1 H).
1-(5-Methyl-2-furanylsulfonyl)-1H-1,2,3-benzotriazole (4n)
White solid; yield: 35%; mp 114–116 °C.
1H NMR (300 MHz, CDCl3): d = 2.32 (s, 3 H), 6.21 (d, J = 3.4 Hz,
1 H), 7.42 (d, J = 3.5 Hz, 1 H), 7.52 (t, J = 7.9 Hz, 1 H), 7.69 (t,
J = 7.8 Hz, 1 H), 8.08 (d, J = 8.4 Hz, 1 H), 8.13 (d, J = 8.4 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 111.9, 119.4, 146.3, 148.2.
HRMS: m/z [M]+ calcd for C4H3N3O3S: 172.9895; found: 172.9887.
13C NMR (75 MHz, CDCl3): d = 14.0, 109.0, 112.1, 120.5, 123.0,
125.9, 130.3, 131.5, 142.5, 145.4, 160.9.
2-Pyridinesulfonyl Azide (5g)23
Pale yellow oil; yield: 90%.
1H NMR (300 MHz, CDCl3): d = 7.60–7.70 (m, 1 H), 8.00–8.04 (m,
2 H), 8.80 (d, J = 4.5 Hz, 1 H).
Anal. Calcd for C11H9N3O3S: C, 50.18; H, 3.45; N, 15.96. Found:
C, 50.29; H, 3.39; N, 15.85.
13C NMR (75 MHz, CDCl3): d = 122.0, 128.3, 138.5, 150.6, 156.9.
Sulfonyl Azides 5a–n; General Procedure
Warning: Due to the explosive character of sulfonyl azides, all
work should be performed in a fume hood, and drying of these com-
pounds should be performed at room temperature.
1-Methyl-1H-imidazole-2-sulfonyl Azide (5h)
Colorless solid; yield: 45%; mp 39–41 °C.
1H NMR (300 MHz, CDCl3): d = 3.97 (s, 3 H), 7.12 (s, 1 H), 7.23
(s, 1 H).
NaN3 (97 mg, 1.5 mmol) was added to a soln of a 1-sulfonylbenzo-
triazole 4a–n (1 mmol) in MeCN (10 mL). One drop of H2O was
added and the mixture was heated under reflux for the time indicat-
ed in Table 2. The solvent was evaporated and the residue was dis-
13C NMR (75 MHz, CDCl3): d = 35.4, 126.5, 129.9, 140.7.
Synthesis 2008, No. 8, 1201–1204 © Thieme Stuttgart · New York

1204
A. Katritzky et al.
PAPER
HRMS: m/z [M + H]+ calcd for C4H6N5O2S: 188.0237; found:
5-Methyl-2-furansulfonyl Azide (5n)
188.0238.
Pale yellow oil; yield: 40%.
1H NMR (300 MHz, CDCl3): d = 2.44 (s, 3 H), 6.22–6.25 (m, 1 H),
7.18 (d, J = 3.6 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 14.0, 108.5, 121.1, 143.9, 160.0.
HRMS: m/z [M]+ calcd for C5H5N3O3S: 187.0046; found: 187.0054.
2-Benzofuransulfonyl Azide (5i)
Pale yellow solid; yield: 23%; mp 58–60 °C.
1H NMR (300 MHz, CDCl3): d = 7.42 (td, J = 7.0, 1.0 Hz, 1 H),
7.55–7.68 (m, 3 H), 7.76 (d, J = 8.1 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 112.7, 115.1, 123.5, 124.9, 125.2,
129.2, 147.8, 156.2.
References
Anal. Calcd for C8H5N3O3S: C, 43.05; H, 2.26; N, 18.83. Found: C,
43.45; H, 2.05; N, 18.47.
(1) Ye, T.; McKervey, M. A. Chem. Rev. 1994, 94, 1091.
(2) Harned, A. H.; Sherrill, W. M.; Flynn, D. L.; Hanson, P. R.
Tetrahedron 2005, 61, 12093.
(3) Charette, A. B.; Wurz, R. P.; Ollevier, T. J. Org. Chem.
2000, 65, 9252.
3-Pyridinesulfonyl Azide (5j)24
Pale yellow oil; yield: 45%.
1H NMR (300 MHz, CDCl3): d = 7.61 (dd, J = 8.1, 4.9 Hz, 1 H),
8.24–8.27 (m, 1 H), 8.95–8.97 (dd, J = 4.8, 1.1 Hz, 1 H), 9.20 (d,
J = 2.0 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 124.1, 135.0, 135.3, 148.0, 155.1.
(4) Wurz, R. P.; Lin, W.; Charette, A. B. Tetrahedron Lett.
2003, 44, 8845.
(5) Panchaud, P.; Renaud, P. Adv. Synth. Catal. 2004, 346, 925.
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(11) Laurent, N.; Lafont, D.; Boullanger, P.; Mallet, J. M.
Carbohydr. Res. 2005, 340, 1885.
5-Ethyl-2-furansulfonyl Azide (5k)
Pale yellow oil; yield: 40%.
1H NMR (300 MHz, CDCl3): d = 1.31 (t, J = 7.6 Hz, 3 H), 2.74–
2.80 (q, J = 7.6 Hz, 2 H), 6.24 (d, J = 3.6 Hz, 1 H), 7.19 (d, J = 3.6
Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 11.4, 21.7, 106.9, 120.9, 143.9,
165.1.
(12) Liu, Q.; Tor, Y. Org. Lett. 2003, 5, 2571.
(13) Farng, L.-p. O.; Kice, J. L. J. Am. Chem. Soc. 1981, 103,
1137.
HRMS: m/z [M + H]+ calcd for C6H8N3O3S: 202.0281; found:
202.0307.
(14) Stefane, B.; Kocevar, M.; Polanc, S. J. Org. Chem. 1997, 62,
7165.
(15) Ofitserov, V. I.; Moksushin, V. S.; Pushkareva, Z. V.;
Nikiforova, N. N. Khim. Geterotsikl. Soedin. 1976, 8, 1119.
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Chem. 2004, 69, 1849.
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Tao, H. J. Org. Chem. 2005, 70, 9191.
(18) Katritzky, A. R.; Abdel-Fattah, A. A. A.; Akhmedova, R. G.
ARKIVOC 2005, (vi), 329.
2-Thiazolesulfonyl Azide (5l)
Pale yellow oil; yield: 25%.
1H NMR (300 MHz, CDCl3): d = 7.83–7.84 (m, 1 H), 8.11 (d,
J = 2.6 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 126.8, 145.3, 162.6.
HRMS: m/z [M + H]+ calcd for C3H3N4O2S2: 190.9692; found:
190.9675.
5-Methyl-2-thiophenesulfonyl Azide (5m)
Pale yellow oil; yield: 30%.
1H NMR (300 MHz, CDCl3): d = 2.60 (s, 3 H), 6.85–6.90 (m, 1 H),
7.63 (d, J = 3.8 Hz, 1 H).
(19) Katritzky, A. R.; Hoffmann, S.; Suzuki, K. ARKIVOC 2004,
(xii), 14.
(20) Katritzky, A. R.; Wang, M.; Zhang, S. ARKIVOC 2001, (ix),
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(23) Buolamwini, J. K.; Knaus, E. E. Eur. J. Med. Chem. 1993,
28, 447.
13C NMR (75 MHz, CDCl3): d = 15.8, 126.5, 134.4, 135.3, 151.6.
HRMS: m/z [M]+ calcd for C5H5N3O2S2: 202.9818; found:
202.9822.
(24) Cremlyn, R. J.; Jones, G. P.; Swinbourne, F. J.; Yung, K.
Phosphorus Sulfur Relat. Elem. 1980, 8, 189.
Synthesis 2008, No. 8, 1201–1204 © Thieme Stuttgart · New York