A mild and efficient method for preparation of azides from alcohols using acidic ionic liquid [H-NMP]HSO4

Article abstract of DOI:10.1016/j.tetlet.2008.11.111

We report here an efficient method for the synthesis and characterization of [H-NMP]HSO₄ and its application as an efficient catalyst and solvent for preparation of azides from corresponding alcohols under mild conditions. This processor showed

Full text of DOI:10.1016/j.tetlet.2008.11.111

Tetrahedron Letters 50 (2009) 708–711
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A mild and efficient method for preparation of azides from alcohols
using acidic ionic liquid [H-NMP]HSO4
b
a
Abdol R. Hajipour a,b, , Asiyeh Rajaei , Arnold E. Ruoho
*
a Department of Pharmacology, University of Wisconsin, Medical School, 1300 University Avenue, Madison, 53706-1532 WI, USA
b Pharmaceutical Research Laboratory, Department of Chemistry, Isfahan University of Technology, Isfahan 84156, Islamic Republic of Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
We report here an efficient method for the synthesis and characterization of [H-NMP]HSO4 and its appli-
cation as an efficient catalyst and solvent for preparation of azides from corresponding alcohols under
mild conditions. This processor showed high chemoselectivity for conversion of various alcohols to their
corresponding azides.
Received 31 October 2008
Revised 26 November 2008
Accepted 26 November 2008
Available online 3 December 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Acidic ionic liquid
Azide
Alcohol
Chemoselective
1. Introduction
for conversion of alcohols to the corresponding azides using
NaN3 (Scheme 1).
Conversions of alcohols to their corresponding azides are very
important and essential in functional group transformation. Alkyl
azides have frequently been used for the synthesis of amino groups
and for the construction of N-heterocycles.1 There are a few re-
ported methods for preparation of alkyl azide including using Mits-
unobu reactions using hydrazoic acid as the azide source,2
oxidation–reduction condensation using a quinone derivative and
trimethylsilylazid (TMSN3),3 N-(p-toluenesulfonyl) imidazole
(TsIm)/tetrabutylammonium iodide (TBAI)/triethylamine (TEA).4
diphenylphosphorazidate (DPPA),5 zinc azid/bis pyridine complex,6
(DPPA)/1, 8-diaza bicyclo[5.4.0]undec-7-en,7, NaN3/BF3ÁET2O,8 and
other useful methods.9,2f Azides have been used for preparation of
medicines such as azido pyrimidines and purines due to their anti
HIV-1 biological activity,10 also 5-azido-5-deoxyxylofuranose has
been employed for synthesis of sugar triazole derivatives as anti
tuberculosis agents.11 Protic acidic ionic liquids (ILs) have fre-
quently been used as green solvents and catalysts in place of con-
ventional organic solvents and acid catalysts.12 In continuation of
our ongoing projects to develop efficient methods for organic func-
tional groups transformation,13–15 here we wish to report the syn-
thesis and characterization of pyrrolidinium bisulfate [H-
NMP]HSO4, which is a new acidic ionic liquid,16 as a highly chemo-
selective, inexpensive, and efficient catalyst and also as a solvent
2. Results and discussion
Initially to optimize the conversion of benzyl alcohol to benzyl
azide, we tried the reaction under solvent-free conditions and in
different solvents such as water, acetonitrile, and dichloromethane
and under different temperatures including 60, 80, 100, and 120 °C
for evaluating the acidity and applications of this Brönsted acid.
Different amounts of acidic ionic liquid and sodium azide were also
tried for optimization of the reaction conditions. We found that
reaction at 120 °C and using 3 mmol of ionic liquid, 1 mmol of ben-
zyl alcohol, and 1.5 mmol of sodium azide gave the best yield in
shorter reaction time. We applied these conditions for synthesis
of various azides from corresponding alcohols (Table 1).17
The procedure showed high chemoselectivity for azidation of
secondary benzyl alcohols in the presence of primary, tertiary ben-
zylic, and also aliphatic alcohols. As demonstrated in Table 1 in
comparison to secondary alcohols with withdrawing groups the
secondary alcohols with donor groups were reacted faster and in
HSO4
O
N
H3C
H
R-N3
R-OH + NaN3
* Corresponding author. Tel.: +98 311 391 3262; fax: +98 311 391 2350.
E-mail address: haji@cc.iut.ac.ir (A.R. Hajipour).
Scheme 1.
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.11.111

A. R. Hajipour et al. / Tetrahedron Letters 50 (2009) 708–711
709
Table 1
Conversion of various alcohols to corresponding azides with optimized procedure
Entry
Substrate
Product
Time (h)
Conversion (%)a
OH
N3
1
6
80
OH
N3
2
12
5
O2N
O2N
OH
N3
3
4
5
8
24
2
40
Cl
Cl
OH
N3
0
OH
OH
N3
100
N3
6
7
2
1
100
100
OMe
N3
OMe
OH
OMe
OMe
OH
N3
8
9
1
3
100
80
MeO
MeO
OH
Cl
N3
Cl
OH
N3
10
11
2
95
Cl
Cl
OH
Br
N3
Br
1.5
100
(continued on next page )

710
A. R. Hajipour et al. / Tetrahedron Letters 50 (2009) 708–711
Table 1 (continued)
Entry
Substrate
Product
Time (h)
Conversion (%)a
OH
N3
12
13
14
1
100
Br
Br
OH
N3
1
1
100
100
Br
Br
OH
N3
H3C
H3C
OH
N3
15
16
17
18
19
1
4
2
1
8
1
100
H3C
CH3
H3C
CH3
N3
OH
OH
40
NO2
NO2
N3
100
OH
N3
90
Cl
Cl
N3
OH
0
OH
N3
20
100
a
Conversions were determined with TLC.
higher yields. Aliphatic alcohols were not converted to their azides
under these conditions (entries 4 and 19) and using alcohols were
recovered without any conversion even in longer reaction times.
We believed that the proton of bisulfate is the proton donor due
to its higher acidity.
3. Conclusion
In conclusion, this method is a novel and convenient method for
conversion of various alcohols to the corresponding azides using
novel and inexpensive acid ionic liquid [H-NMP]HSO4. The high

A. R. Hajipour et al. / Tetrahedron Letters 50 (2009) 708–711
711
9. For example, see: (a) Mizuno, M.; Shioiri, T. Chem. Commun. 1997, 2165; (b) Yu,
C.; Liu, B.; Hu, L. Org. Lett. 2000, 2, 1959; (c) Iranpoor, N.; Firouzabadi, H.;
Akhlaghinia, B.; Nowrouzi, N. Tetrahedron Lett. 2004, 45, 3291.
10. Kim, H. O.; Park, Y. H.; Moon, H. R.; Jeong, L. S. Bioorg. Med. Chem. Lett. 2002,
2403.
11. Singh, B. K.; Yadav, A. K.; Kumar, B.; Gaikwad, A.; Sinha, S. K.; Chaturvedi, V.;
Tripathi, R. P. Carbohydr. Res. 2008, 343, 1153.
12. (a) Tamar, L. G.; Calum, J. Chem. Rev. 2008, 108, 206; (b) Johnson, K. E.; Richard,
R. M.; Pagni, M.; Bartmess, J. Monatsh. Chem. 2007, 138, 1077.
yield, green chemistry, using inexpensive and straightforward
isolation of the products are the advantages of this method over
reported procedures. The method is chemoselective for conversion
of secondary benzylic alcohols in the presence of primary benzylic
and aliphatic alcohols and also for conversion of primary benzylic
alcohols in the presence of aliphatic alcohols. In this method, the
halogen groups in benzene rings were intact during the reaction.
13. Hajipour, A. R.; Zarei, A.; Khazdooz, L.; Mirjalili, B. B. F.; Sheikhan, N.;
Zahmatkesh, S.; Ruoho, A. E. Synthesis 2005, 20, 3644.
Acknowledgments
14. (a) Hajipour, A. R.; Arbabian, M.; Ruoho, A. E. J. Org. Chem. 2002, 67, 8622; (b)
Hajipour, A. R.; Ruoho, A. E. Org. Prep. Proced. Int. 2002, 34, 647; (c) Hajipour, A.
R.; Mazloumi, G. Synth. Commun. 2002, 32, 23; (d) Hajipour, A. R.; Ruoho, A. E. J.
Chem. Res. (S) 2002, 547; (e) Hajipour, A. R.; Adibi, H.; Ruoho, A. E. J. Org. Chem.
2003, 68, 4553; (f) Hajipour, A. R.; Bageri, H.; Ruoho, A. E. Bull. Korean Chem.
Soc. 2004, 25, 1238; (g) Hajipour, A. R.; Malakutikhah, M. Org. Prep. Proced. Int.
2004, 364, 647; (h) Hajipour, A. R.; Ruoho, A. E. Sul. Lett. 2002, 25, 151; (i)
Hajipour, A. R.; Mirjalili, B. F.; Zarei, A.; Khazdooz, L.; Ruoho, A. E. Tetrahedron
Lett. 2004, 45, 6607; (a) Hajipour, A. R.; Mahboubkhah, N. J. Chem. Res. (S) 1998,
122; (b) Hajipour, A. R.; Mallakpour, E.; Adibi, H. Chem. Lett. 2000, 460; (c)
Hajipour, A. R.; Mallakpour, E.; Khoee, S. Chem. Lett. 2000, 120; (d) Hajipour, A.
R.; Mallakpour, E.; Khoee, S. Synlett 2000, 740; (e) Hajipour, A. R.; Ruoho, A. E.
Org. Prep. Proced. Int. 2005, 37, 298; (f) Hajipour, A. R.; Ruoho, A. E. Org. Prep.
Proced. Int. 2005, 37, 279.
We gratefully acknowledge the funding support received for
this project from the Isfahan University of Technology (IUT), IR Iran
(A.R.H.) and Grant GM 33138 (A.E.R.) from the National Institutes
of Health, USA. Further financial support from Center of Sensor
and green chemistry Research (IUT) is gratefully acknowledged.
References and notes
1. (a) Brase, S.; Gil, C.; Knepper, K.; Zimmermann, V. Angew. Chem., Int. Ed. 2005,
44, 5188–5240; (b) Scriven, E. F. V.; Turnbull, K. Chem. Rev. 1988, 88, 297; (c)
Boyer, J. H.; Canter, F. C. Chem. Rev. 1954, 54, 1; (d) Smith, P. A. S.. In Open Chain
Nitrogen Compounds; W.A. Benjamin: New York, 1966; Vol. II, p 211.
2. (a) Mitsunobu, O.; Wada, M.; Sano, T. J. Am. Chem. Soc. 1972, 94, 679; (b)
Hughes, D. L. Org. React. 1992, 42, 358–359; (c) Loibner, H.; Zbiral, E. Helv. Chim.
Acta 1977, 60, 417; (d) Mitsunobu, O. Synthesis 1981, 1; (e) Hughes, D. L. Org.
Prep. Proced. Int. 1996, 28, 127; (f) Saito, A.; Saito, K.; Tanaka, A.; Oritani, T.
Tetrahedron Lett. 1997, 38, 3955; (g) Mizuno, M.; Shior, T. Chem. Commun. 1997,
2165; (h) Fabiano, E.; Golding, B. T.; Sadeghi, M. M. Synthesis 1987, 190; (i)
Bessodes, M.; Abushanab, E.; Antonakis, K. Tetrahedron Lett. 1984, 25, 5899; (j)
Mitsunobu, O. Bull. Chem. Soc. Jpn. 1967, 40, 4235; (k) Lee, S.-H.; Yoon, J.; Chung,
S.-H.; Lee, Y.-S. Tetrahedron 2001, 57, 2139.
3. Kurada, K.; Hayashi, Y.; Mukaiyama, T. Tetrahedron 2007, 63, 6358.
4. Soltani Rad, M. N.; Behrouz, S.; KHalafi Nejad, A. Tetrahedron Lett. 2007, 48,
3445.
5. Lal, B.; Pramanik, B. N.; Manhas, M. S.; Bose, A. K. Tetrahedron Lett. 1977, 1977.
6. Viaud, M. C.; Rollin, P. Synthesis 1990, 130.
7. Thompson, A. S.; Humphrey, G. R.; Demarco, A. M.; Mathre, D. J.; Grabowski, J. J.
J. Org. Chem. 1993, 58, 5886.
8. Sampath Kumar, H. M.; Subba Reddy, B. V.; Anjaneyulu, S.; Yadav, J. S.
15. Hajipour, A. R.; Kooshki, B.; Ruoho, A. E. Tetrahedron Lett. 2005, 46, 5503.
16. Synthesis of acidic ionic liquid [H-NMP]HSO4: In a round-bottomed flask, to a
cold mixture of 1-methyl-2-pyrrolidone, (0.99 g) in 15 ml of dichloromethane
on an ice bath was added. One gram of concentrated sulfuric acid (98%,
d = 1.84) was added dropwise. The reaction mixture was stirred at room
temperature for 3 h, then the solvent was evaporated under reduce pressure to
produce 1.97 g of [H-NMP]HSO4 (100%). FT-IR (KBr, cmÀ1) 2300–3600 (s, Br),
1660 (s), 1509 (m), 1302 (m), 1114 (w), 962 (w), 610 (w) cmÀ1 1H NMR
.
(500 MHz, D2O): d 1.4 (m, 2H, CH2), 1.8 (t, 2H, CH2), 2.2 (s, 3H, CH3), 2.9 (t, 2H,
CH2). 13C NMR (500 MHz, D2O): d 22.22 (CH2), 35.09 (CH2), 42.10–43.51 (CH2,
CH3), 180 (C@O) ppm.
17. General procedure for the one-pot conversion of alcohol to azide: In a 25 ml
round-bottomed flask, a mixture of alcohol (1 mmol), NaN3 (1.5 mmol), and
ionic liquid [H-NMP]HSO4 (3 mmol) was stirred on an oil bath at 120 °C. The
progress of the reaction was checked with TLC (cyclohexane/ethyl acetate
70:30). When the reaction was completed, the mixture was extracted with
cyclohexane (2 Â 10 ml), filtered off the solid. The organic layer was washed
with NaOH 5% (10 ml). The organic phase was dried with MgSO4, and the
solvent was evaporated under reduced pressure. The crude product was
purified by column chromatography using silica gel (cyclohexane/ethyl acetate
70:30).
Tetrahedron Lett. 1998, 39, 7385.