1-butyl-3-methylimidazolium nitrite as a reagent for the efficient n-nitrosation of secondary amines

Article abstract of DOI:10.1007/BF03245916

1-Butyl-3-methylimidazolium nitrite, [bmim]NO₂ was used as a new effective reagent for the preparation of N-nitrosamines from the corresponding secondary amines at 0 °C to room temperature, under mild conditions in good to excellent yields.

Full text of DOI:10.1007/BF03245916

J. Iran. Chem. Soc., Vol. 8, No. 3, September 2011, pp. 857-861.
JOURNAL OF THE
Iranian
Chemical Society
1
-Butyl-3-methylimidazolium Nitrite as a Reagent for the Efficient N-Nitrosation of
Secondary Amines
H. Valizadeh* and H. Gholipour
Department of Chemistry, Faculty of Sciences, Azarbaijan University of Tarbiat Moallem, Tabriz, Iran
(
Received 10 December 2010, Accepted 18 January 2011)
1
-Butyl-3-methylimidazolium nitrite, [bmim]NO was used as a new effective reagent for the preparation of N-nitrosamines
2
from the corresponding secondary amines at 0 °C to room temperature, under mild conditions in good to excellent yields.
Keywords: N-Nitrosation, Secondary amines, N-Nitrosoamines, Task-specific ionic liquid
INTRODUCTION
been successfully used as solvents and/or catalysts in several
classical organic processes [17-19]. Ionic liquids containing
specific functional groups, known as task-specific ionic liquids
(TSILs), can be used as reagent and/or catalyst and as reaction
medium, which further enhances the versatility of ionic liquids
[20-22]. Haihong and co-workers used task-specific basic
ionic liquid immobilized on mesoporous silicas as an efficient
and reusable catalyst for Knoevenagel condensation in
aqueous media [23]. Hajipour et al. prepared aldoximes using
in situ prepared ionic liquids under convenient conditions [24].
N-Nitrosoamines as important organic compounds have
attracted considerable interest in recent years due to their
strong mutagenic and carcinogenic properties [1] and are
prepared via the N-nitrosation of amines. These compounds
are involved in vasorelaxant activity and have been used as
pesticides [2]. These useful synthetic intermediates have been
used for the synthesis of various N,N-bonded functionalities.
From among a variety of reported nitrosating agents, nitrous
acid, generated from sodium nitrite and mineral acid in water
or in mixed alcohol-water solvents, is mostly used for the
nitrosation of amines [3]. Nitrosyl salts [4], alkyl nitrites [5],
dinitrogen tetroxide [6], oxyhyponitrite [7], Fremy’s salt [8],
N-haloamides and sodium nitrite under phase-transfer
Recently we used the TSIL-OPPh as a weak Lewis base
2
catalyst and reaction medium for the Biginelli and
Knoevenagel reactions as well as in the synthesis of nitrones
[25-27]. We also reported the diazotization of anilines using a
new nitrite ionic liquid (IL-ONO) and the subsequent azo-
coupling for the efficient preparation of azo dyes [28]. We
wish to report here the efficient N-nitrosation of secondary
amines 1a-n using task-specific nitrite ionic liquid,
conditions [9], bis(triphenylphosphine) ammonium nitrite
-
[
10], solid acids [11-13], [NO+. Crown. H (NO
silica chloride/NaNO
reagents in literature. The application of N
reactions was recently reported by Shiri et al. [16].
3
)
2
] [14], and
2
[15] are also reported as nitrosating
/NO in organic
2
O
4
2
[bmim]NO under mild conditions. (Scheme 1).
2
On the other hand, room temperature ionic liquids are very
attractive alternatives to volatile solvents due to their very low
vapor pressure and being thermally stable. Ionic liquids have
EXPERIMENTAL
General
All reagents were purchased from Merck Company and
used without further purification. Infrared spectra were
*Corresponding author. E-mail: h-valizadeh@azaruniv.edu

Valizadeh & Gholipour
Found (%): C, 52.12; H, 8.21; N, 22.58.
General Procedure for N-Nitrosation Using New
Nitrite Ionic Liquid
Method A. Secondary amine (10 mmol) and concentrated
hydrochloric acid (12.5 mmol) were mixed in water or
alcohol-water solvent and stirred vigorously at 5 °C. While
Scheme 1. 1-Butyl-3-methylimidazolium nitrite as a new
reagent for the nitrosation of secondary amines
stirring the mixture, a solution of [bmim]NO (11 mmol) in
2
water (3 ml) was added gently and stirring was continued for
3
0 min at 5-25 °C. The precipitate, N-nitrosamine, was filtered
recorded in KBr and were determined on a Perkin Elmer FT-
1
13
and washed with cold water. For the soluble nitrosamines in
water, NaCl was added for precipitation of the products. The
crude product was recrystallyzed from EtOH/AcOEt to obtain
pure nitrosamine. If required, this product is further purified
by flash chromatography on silica gel using ethylacetate/
petroleum ether (1:7) as eluent.
IR spectrometer. H and C NMR spectra were recorded on a
Bruker Avance AC-400 MHz using CDCl or DMSO-d as the
3
6
deuterated solvent and TMS as the internal standard.
Elemental analyses were carried out on a Perkin-Elmer 240C
elemental analyzer and are reported in percent atomic
abundance. All melting points were measured in open glass-
capillaries using Stuart melting point apparatus.
Method B. A mixture of secondary amine (10 mmol),
[
bmim]NO (11 mmol) and acetic acid (12.5 mmol) in
2
dichloromethane (5 ml) was stirred vigorously at room
temperature till the completion of the reaction as indicated by
TLC. After the completion of the reaction, the solvent was
evaporated and the crude product was purified by
recrystallization from EtOH/EtOAc to obtain the related N-
nitroso product 2a-n (Table 1). If required, this product was
further purified by flash chromatography on silica gel using
ethylacetate/petroleum ether (1:7) as eluent.
Preparation of 1-Butyl-3-methylimidazolium Nitrite,
[
bmim]NO2
1
-Butyl-3-methylimidazolium chloride was prepared from
the reaction of N-methylimidazole with n-butylchloride at 80
C under neat conditions. Sodium nitrite (23 mmol) was added
°
to a solution of this freshly prepared ionic liquid (20 mmol) in
dichloromethane (10 ml) and stirred for 24 h at room
temperature. The suspension was filtered to remove the
precipitated sodium chloride salt and the organic layer was
washed with water (3 × 8 ml) to the extent that no
precipitation of AgCl occurred in aqueous phase on addition
RESULTS AND DISCUSSION
of a concentrated AgNO solution. The solvent and other
The ionic liquid, 1-butyl-3-methylimidazolium nitrite was
prepared from 1-butyl-3-methylimidazolium chloride by the
exchange of chloride anion with nitrite anion in contact with
sodium nitrite solution at room temperature in 80% yield. The
3
volatile materials were removed from organic layer under
vacuum and the resulting ionic liquid was stirred with
activated charcoal for 12 h, after which the ionic liquid was
passed through a short alumina column(s) (acidic and/or
neutral) to give a colorless ionic liquid, which was dried at 100
[bmim]NO was then evaluated as the nitrosonium source for
2
the nitrosation of secondary amines in the presence of an acid.
As a typical experiment, dibenzylamine was chosen as a
model secondary amine. While stirring the mixture of an
equimolar amount of dibenzylamine and HCl 37% in water,
°C under vacuum for 24 h or until there was no visible signs of
water in the IR spectrum. Yields 80%. IR (KBr): 1652, 1617,
-
1
1
1
1
532, 1350, 1190 Cm ; H NMR (400 MHz, DMSO-d ) δ
6
.05 (3H, t, -CH ), 1.41 (2H, m, CH ), 1.76 (2H, m, CH ), 3.83
[bmim]NO was added at 5-25 °C. TLC monitoring showed
2
3
2
2
(
(
3H, s, N-CH ), 3.97 (2H, t, -N-CH ), 7.21 (1H, d, Ar-H), 7.40
the completion of the reaction after 25 min and the related N-
nitrosamine product, N-nitrosodibenzylamine 2f, was isolated
in 85% yield. The stable N-nitroso product was characterized
3
2
1H, d, Ar-H), 9.12 (1H, broad, Ar-H). 13C NMR (100 MHz,
) 11.7, 18.3, 25.6, 36.4, 37.8, 124.7, 126.8, 140.0.
Anal. Calcd. (%) for C : C, 51.88; H, 8.16; N, 22.69.
DMSO-d
6
1
H
15
N
3
O
2
by FT-IR and H NMR spectroscopy and elemental analysis.
8
8
58

1-Butyl-3-methylimidazolium Nitrite as a Reagent
Table 1. 1-Butyl-3-Methylimidazolium Nitrite as a New Reagent for the Efficient N-Nitrosation of Secondary Amines
Entry
Substrate
Nitrosamine
Product
number
Time(min)
Yield (%)a
Method Method Method Method
A
B
A
B
1
2
3
4
5
6
7
Me NH
2
Me NNO
2
2a
2b
2c
2d
2e
2f
30
30
35
30
25
30
32
35
35
45
40
30
40
40
89
85
88
82
91
90
92
86
86
88
84
88
88
90
2
2
Et
NH
Et NNO
Bu NH
Bu NNO
2
2
(i-propyl)
2
NH
(i-propyl) NNO
2
Ph NH
Ph NNO
2
2
(PhCH ) NH
(PhCH ) NNO
2
2
2 2
PhNHMe
PhN(NO)Me
2g
8
2h
40
50
83
80
N
H
N
NO
9
PhCH NHEt
PhCH
PhCH
2
N(NO)Et
2i
2j
30
35
35
45
85
83
82
80
2
1
0
1
PhCH NHMe
2
N(NO)Me
2
NHMe
NHMe
Me
N
1
NO
2K
30
35
88
87
Cl
Cl
Me
N
NO
1
2
3
2l
32
30
40
35
92
90
91
85
O
2
N
O
2
N
Me
N
NHMe
1
NO
2m
NO
2
NO
2
14
2n
35
35
87
87
NH
NNO
aIsolated yield.
Optimization of the reaction conditions was studied with
different molar ratios of the HCl, ionic liquid and
dibenzylamine. The best ratio was found to be 1.25:1.10:1.
Under optimized conditions, the product 2f was prepared in
nitrosation of secondary amines, since a comparatively higher
yield was produced in a shorter reaction time (Method B,
Table 1). This ionic liquid was then used for the nitrosation of
different secondary amines under optimized conditions via the
two methods. For comparison, the results from the two
methods are presented in Tables 1 and 2.
Chemoselectivity of these methods was determined via the
competitive reaction which took place between diphenylamine
and anisole. It was observed that N-nitrosation versus
9
0% yield (Method A, Table 1). We examined this procedure
in various organic solvents using several organic acids such as
AcOH, benzenesulfonic acid and benzoic acid as catalysts.
From the results obtained, it was clear that the reaction in
dichloromethane using AcOH should be the one for the
8
59

Valizadeh & Gholipour
Table 2. Melting/Boiling Points of the Products
Product number Melting point (°C)
-1
Boiling point (°C mmHg )
Found
-
Reported [Lit.]
-
Found
154/774
Reported [Lit.]
152.5/774 [29]
2
2
2
2
2
2
2
2
2
2
2
2
2
a
b
c
d
e
f
-
-
175-177
177 [29]
-
-
115/14
116-117.5/14 [30]
44-46
46-48 [29]
-
-
-
64-66
65-66.5 [3]
-
57.5-59
57-59 [31]
-
-
a
g
h
i
-
-
129/19
127-128/19 [29]
213-214 [29]
309-310.5 [32]
298-299.2 [33]
Colorless oil ([34]
-
-
-
215
-
-
312
299
b
j
-
-
c
k
-
-
Colorless oil
-
d
l
100-101
-
103 [35]
-
e
m
Pale yellow oil
Pale yellow oil
(
[36]
f
2
n
-
-
Colorless oil
Colorless oil ([37]
a
b
c
The ratio of two isomers is 3.02:1. The ratio of two isomers is 2.89:1. The ratio of two isomers is
.29:1. The ratio of two isomers is 2.9:1. The ratio of two isomers is 3:1. The ratio of two isomers is
.45:1.
d
e
f
2
2
electrophlic aromatic nitrosation occurred selectively and
anisole remained intact in the reaction mixture after 1 h.
In summary, task-specific ionic liquid, 1-butyl-3-
methylimidazolium nitrite was used as an effective
nitrosonium source for the nitrosation of secondary amines
under convenient conditions. The advantages of this protocol
are mild reaction conditions, short reaction times, simple
work-up procedure and good to excellent yields.
for Research of Azarbaijan University of Tarbiat Moallem is
gratefully acknowledged.
REFERENCES
[1]
[2]
[3]
[4]
L. Garcia-Rio, J.R. Leis, E. Issglesias, J. Org. Chem. 62
(1997) 4712.
N.S. Nudelman, A.E. Bonatti, Synlett. (2000) 1825, and
references cited therein.
th
ACKNOWLEDGMENTS
Vogels Text Book of Practical Organic Chemistry 4
ed., Longman, London and New York, 1986.
G.A. Olah, Aldrichimica. Acta 12 (1979) 43.
The partial financial assistance from the Vice Chancellor
8
60

1-Butyl-3-methylimidazolium Nitrite as a Reagent
[
[
5]
6]
H. Lecher, W. Siefhen, Chem. Ber. 59 (1926) 2594.
N.N. Makhora, G.A. Karpov, A.N. Mikhailyuk, A.E.
Bova, L.I. Khmel’nitskii, S.S. Novikov, lzv. Akad.Nauk
SSSR, Ser. Khim. 1 (1978) 226.
S.K. Chang, G.W. Hrrington, M. Rothstein, W.A.
Shergalis, D. Swern, S.K. Vohra, Cancer. Res. 39
(2009) 159.
[22] J.-M. Xu, B.-K. Liu, W.-B. Wu, C. Qian, Q. Wu, X.-F.
Lin, J. Org. Chem. 71 (2006) 3991.
[23] H. Zhao, N. Yu, Y. Ding, R. Tan, C. Liu, D. Yin, H.
Qiu, D. Yin, Microporous, Mesoporous Materials 136
(2010) 10.
[
7]
(
1979) 3871.
[24] A.R. Hajipour, F. Rafiee, A.E. Ruoho, J. Iran. Chem.
Soc. 7 (2010) 114.
[25] H. Valizadeh, A. Shockravi, Heteroatom. Chem. 20
(2009) 284.
[26] H. Valizadeh, H. Gholipour, Synth. Commun. 40
(2010) 1477.
[27] H. Valizadeh, Heteroatom. Chem. 21 (2010) 78.
[28] H. Valizadeh, A. Shomali, Dyes Pigments, 2010,
Accepted for Publication. doi: 10.1016/j.dyepig.
2010.11.010.
[
[
[
8]
9]
L. Castedo, R. Riguera, M.P. Vázquez, J. Chem. Soc.
Chem. Commun. (1983) 301.
M. Nakajima, J.C. Warner, J.P. Anselme, Tetrahedron
Lett. 25 (1984) 2619.
10] J.C. Fanning, L.K. Keefer, K. Larry, J. Chem. Soc.
Chem. Commun. (1987) 955.
11] M.A. Zolfigol, Synth. Commun. 29 (1999) 905.
12] M.A. Zolfigol, E. Ghaemi, E. Madrakian, M. Kiany-
Borazjani, Synth. Commun. 30 (2000) 2057.
[
[
[
13] M.A. Zolfigol, F. Shirini, A. Ghorbani-Choghamarani,
A. Taqiannasab, H. Keypour, S. Salehzadeh, J. Chem.
Res. (S) (2000) 420.
14] M.A. Zolfigol, M.H. Zebarjadian, G. Chehardoli, H.
Keypour, S. Salehzadeh, M. Shamsipur, J. Org. Chem.
[29] I. Heilbron, H.M Bunbury, Dictionary of Organic
Compounds, London, 1953.
[30] F.L. Boca Raton, CRC Handbook of Chemistry and
Physics, CRC Press, 1979.
[31] J.R.L. Smith, M.W. Nee, J.B. Noar, T.C. Bruice, J.
Chem. Soc. Perkin Trans. 2 (1984) 255.
[32] http://www.lookchem.com/N-nitroso-n-ethyl-
benzylamine.
[33] D. Seebach, D. Enders, Chem. Ber. 108 (1975) 1293.
[34] M.B. Kroeger-Koepke, A.W. Andrews, R.J. Kupper,
S.R. Koepke, C. Michejda, J. Mutat. Res. 89 (1981)
255.
[
6
6 ( 2001) 3619.
[
[
[
[
15] M.A. Zolfigol, F. Shirini, A.G. Choghamarani, Synth.
Commun. 32 (2002) 1809.
16] M. Shiri, M.A. Zolfigol, G.H. Kruger, Z.
Tanbakouchian, Tetrahedron 66 (2010) 9077.
17] M. Movahedi, E. Kowsari, A.R. Mahjoub, I. Yavari,
Materials Lett. 62 (2008) 3856.
18] F. Dong, G. Kai, F. Zhenghao, Z. Xinli, L. Zuliang,
Catal. Commun. 9 (2008) 317.
[35] B.G. Gowenlock, J. Pfab, V.M. Young, J. Chem. Soc.
Perkin Trans. 2 (1997) 915.
[
[
19] S.R. Roy, A.K. Chakraborti, Org. Lett. 12 (2010) 3866.
20] A.R. Hajipour, F. Rafiee, J. Iran. Chem. Soc. 6 (2009)
[36] R.L. Williams, R.J. Pace, G.L. Jeacocke, Spectrochim.
Acta 20 (1964) 225.
6
47.
[37] D. Seebach, D. Enders, Angew. Chem. Int. Ed. Engl. 11
(1972) 301.
[
21] H. Tajik, K. Niknam, F. Parsaa, J. Iran. Chem. Soc. 6
8
61