Ionic liquid 1-(4-nitritobutyl)-3-methylimidazolium chloride as a new reagent for the efficient N-nitrosation of secondary amines under mild conditions

Article abstract of DOI:10.1007/s00706-011-0574-7

1-(4-Nitritobutyl)-3-methylimidazolium chloride has been developed as a new reagent for efficient nitrosation of secondary amines at 0 °C to room temperature. A variety of N-nitrosamines were prepared in excellent yields by use of this task-specific ionic liquid under mild and heterogeneous conditions.

Full text of DOI:10.1007/s00706-011-0574-7

Monatsh Chem (2012) 143:467–470
DOI 10.1007/s00706-011-0574-7
ORIGINAL PAPER
Ionic liquid 1-(4-nitritobutyl)-3-methylimidazolium chloride
as a new reagent for the efficient N-nitrosation of secondary
amines under mild conditions
•
Hassan Valizadeh Hamid Gholipour
•
Ashkan Shomali
Received: 24 December 2010 / Accepted: 12 July 2011 / Published online: 16 August 2011
Ó Springer-Verlag 2011
Abstract 1-(4-Nitritobutyl)-3-methylimidazolium chlo-
ride has been developed as a new reagent for efficient
nitrosation of secondary amines at 0 °C to room tempera-
ture. A variety of N-nitrosamines were prepared in
excellent yields by use of this task-specific ionic liquid
under mild and heterogeneous conditions.
synthesized flavones in [bmim]BF4 ionic liquid. Hajipour
and co-workers reported a convenient method for prepa-
ration of aldoximes in the presence of in-situ-prepared
ionic liquids [9]. Very recently we used an imidazolium-
based phosphinite ionic liquid (TSIL-OPPh2) as a weak
Lewis base catalyst and reaction medium for the Biginelli
and Knoevenagel reactions and also in the synthesis of
nitrones [10–12]. We also used a task-specific phosphinite
ionic liquid as reagent and reaction medium for one-pot
Horner–Wadsworth–Emmons-type reactions under micro-
wave irradiation [13].
Keywords N-Nitrosation Á Secondary amines Á
N-Nitrosoamines Á Task-specific ionic liquid
Introduction
N-Nitrosation of amines is an important reaction in
organic synthesis. N-Nitrosoamines, which are important
organic compounds because of their strong mutagenic and
carcinogenic properties [14], have attracted much interest
in recent years. These compounds have vasorelaxant
activity and have been used as pesticides [15]. A variety of
N,N-bonded functionality has been synthesized from these
useful synthetic intermediates. A variety of nitrosating
agents have been reported for nitrosation of amines. The
most general reagent, nitrous acid, is generated from
sodium nitrite and mineral acid in water or in mixed
alcohol–water solvents [16]. Other nitrosating reagents
Room-temperature ionic liquids (RTILs) are a powerful
alternative to conventional molecular organic solvents or
catalysts because of specific properties such as undetect-
able vapor pressure, wide liquid range, and ease of
recovery and reuse [1–5]. Incorporation of additional
functional groups as a part of the cation and/or anion of
ionic liquids has led to functionalized ionic liquids, so-
called task-specific ionic liquids (TSILs), which have
recently attracted chemists’ interest. TSILs have been used
not only as alternative green solvents, but also as reagents
and/or catalysts in synthetic organic chemistry. Wang and
Li used TSIL as Lewis base, ligand, and reaction medium
for the palladium-catalyzed Heck reaction [4]. Paun and
Barklie reported the basic ionic liquid-catalyzed Knoeve-
nagel condensation reaction [6]. Tajik and co-workers
reported the nitration of phenols using an acidic ionic
liquid under mild conditions [7]. Pawar et al. [8]
Me
Cl
N
N
O
IL-ONO =
NO
IL-ONO, HCl
0-25 °C
R1R2NH3 Cl
R1R2N-N=O
H. Valizadeh (&) Á H. Gholipour Á A. Shomali
Department of Chemistry, Faculty of Sciences,
Azarbaijan University of Tarbiat Moallem, Tabriz, Iran
e-mail: hvalizadeh2@yahoo.com
1a-1n
2a-2n
Scheme 1
123

468
H. Valizadeh et al.
Yielda/%
Table 1 1-(4-Nitritobutyl)-3-methylimidazolium chloride as a new reagent for efficient N-nitrosation of secondary amines
Entry
Substrate
Product
Time/min
1
2
3
4
5
6
7
8
Me2NH
Et2NH
Me2NNO
2a
2b
2c
2d
2e
2f
70
70
60
60
70
65
65
70
92
92
94
94
95
97
95
89
Et2NNO
Bu2NH
Bu2NNO
i-Pr2NH
Ph2NH
i-Pr2NNO
Ph2NNO
(PhCH2)2NH
PhNHMe
(PhCH2)2NNO
PhN(NO)Me
2g
2h
N
H
N
NO
9
PhCH2NHEt
PhCH2NHMe
PhCH2N(NO)Et
PhCH2N(NO)Me
2i
65
70
85
90
92
85
10
11
2j
2k
NHMe
Me
N
NO
Cl
Cl
12
2l
90
90
NHMe
Me
N
NO
O2N
O2N
13
14
2m
90
70
89
93
NHMe
Me
N
NO
NO2
NO2
2n
NNO
NH
a
Isolated yield
include nitrosyl salts [17], alkyl nitrites [18], dinitrogen
tetroxide [19], oxyhyponitrite [20], Fremy’s salt [21],
N-haloamides and sodium nitrite under phase-transfer
conditions [22], bis(triphenylphosphine) ammonium
nitrite [23], solid acids [24–26], and sodium nitrite
(NO?ÁcrownÁH(NO3)2- ) [27], silica chloride/NaNO2 [28],
and polymeric nitrosation reagents [29, 30].
N-nitrosamines by reaction of secondary amines with a
task-specific nitrite ionic liquid as reagent in a solventless
system (Scheme 1).
Results and discussions
We wished to develop a new nitrosating agent. In a
continuation of our study of organic reactions under green
conditions [10–13], we wish to report here the synthesis of
The ionic liquid 1-(4-nitritobutyl)-3-methylimidazolium
nitrite (IL-ONO) was synthesized in accordance with our
very recent publication [31].
123

Ionic liquid 1-(4-nitritobutyl)-3-methylimidazolium chloride as a new reagent
469
IL-ONO was then evaluated as nitrosonium source for the
nitrosation of secondary amines. Nitrosation of dibenzyl-
amine was chosen as a model study. A solution of 4.94 g
IL-ONO (22.5 mmol) and 0.92 cm3 HCl (37%, 30 mmol) in
5 cm3 water was added dropwise to a flask containing a
stirred aqueous solution of 2.95 g dibenzylamine (15 mmol)
and 1.23 cm3 HCl (37%, 40 mmol) at 0 °C. TLC monitoring
showed completion of the reaction in 1 h. The stable
secondary amines, for example 2i, exist as two rotational
isomers because of restricted rotation of the N–N bond.
Conclusion
In summary, the task-specific nitrite ionic liquid 1-(4-ni-
tritobutyl)-3- methylimidazolium chloride has been used as
an effective reagent for nitrosation of secondary amines
under mild heterogeneous conditions. The advantages of
this procedure are mild reaction conditions, short reaction
times, simple work-up procedure, free of organic solvent,
and good yields. Therefore, we believe that the new syn-
thetic method reported here would greatly contribute to
environmentally greener and safer processes.
1
N-nitroso product was characterized by H NMR spectros-
copy and comparison of its melting point with the reported
value. Different types of secondary amine were subjected to
nitrosation in the presence of IL-ONO. The nitrosation
reactions were performed at 0–25 °C and took place with
good to excellent yields (Table 1). A competitive reaction
performed between diphenylamine and anisole showed the
chemoselectivity of this method. It was observed that amine
nitrosation occurred whereas anisole remained intact in the
reaction mixture after 1 h. Melting/boiling points of
the products are listed in Table 2. The results showed that
N-nitrosation occurred faster than electrophilic aromatic
nitrosation. Water-insoluble amines were reacted effec-
tively under heterogeneous conditions. NMR spectra
showed that products of asymmetrically substituted
Experimental
All reagents were purchased from Merck and used without
further purification. Infrared spectra were recorded in KBr
and were determined on a Perkin–Elmer FT-IR spectrom-
1
eter. H NMR spectra were obtained in CDCl3 solution
from a Bruker Avance AC-400 MHz and 13C NMR spectra
at 100 MHz on the aforementioned instrument. Elemental
analysis was carried out on a Perkin–Elmer 240C elemental
analyzer and is reported in percentage atomic abundance.
All melting points were measured in open glass-capillaries
using a Stuart melting-point apparatus.
Table 2 Physical data for products 2a–2n
Product Melting point/°C
Boiling point/°C/mbar
Found Reported
Found
Reported
2a
2b
–
–
–
–
154 (1,013)
152.5 (1,013) [32]
177 (1,013) [32]
175–177
(1,013)
General procedure for nitrosation of secondary amines
using IL-ONO
2c
2d
2e
–
–
102–104 (11) 103–104 (11) [32]
44–46 47–48 [32]
–
–
–
–
64–66 65–66.5
[16]
Secondary amine (15 mmol) and concentrated hydrochloric
acid (40 mmol) were added to water or mixed alcohol–water
(5 cm3) and mixed vigorously at 0 °C. While stirring the
mixture, a solution of 4.94 g IL-ONO (22.5 mmol) in 3 cm3
water was added slowly. The reaction mixture was left
stirring at room temperature for the time shown in Table 1.
The products were isolated by filtration and washed three
times with cold water to afford the crude N-nitrosamines.
The crude products were purified by recrystallization from
ethyl acetate–n-hexane. Products 2 h and 2n were purified
by flash chromatography on silica gel.
2f
57.5–59 57–59 [33]
–
–
2ga
–
–
–
–
129–131 (25) 129 (25) [32]
2h
215 (1,013)
213–214 (1,013)
[32]
[34]g
2i
2jb
–
–
–
–
312 (1,013)
299 (1,013)
298–299.2 (1,013)
[35]
[36]g
2kc
2ld
2me
2nf
a
–
–
309 (1,013)
–
99–102 103 [37]
–
–
–
–
–
349 (1,013)
316 (1,013)
[38]g
[39]g
Acknowledgments Financial support of this work by the research
affairs of Azarbaijan University of Tarbiat Moallem is gratefully
acknowledged.
The ratio of the two isomers is 3.02:1
The ratio of the two isomers is 2.89:1
The ratio of the two isomers is 2.29:1
The ratio of the two isomers is 2.9:1
The ratio of the two isomers is 3:1
The ratio of the two isomers is 2.45:1
Reference to NMR data
b
c
d
e
f
References
1. Gong K, Fang D, Wang H-L, Zhou X-L, Liu Z-L (2009) Dyes
Pigm 80:30
g
123

470
H. Valizadeh et al.
2. Le Z-G, Chen Z-C, Hu Y, Zheng Q-G (2004) Synthesis 2809
3. Yue C, Mao A, Wei Y, Lu¨ M (2008) Catal Commun 9:1571
4. Wang L, Li H, Li P (2009) Tetrahedron 65:364
5. Macfarlane DR, Pringle JM, Johansson KM, Forsyth SA, Forsyth
M (2006) Chem Commun 1905
6. Paun C, Barklie J, Goodrich P, Gunaratne HQN, McKeown A,
22. Nakajima M, Warner JC, Anselme JP (1984) Tetrahedron Lett
25:2619
23. Fanning JC, Keefer LK, Larry K (1987) J Chem Soc Chem
Commun 955
24. Zolfigol MA (1999) Synth Commun 29:905
25. Zolfigol MA, Ghaemi E, Madrakian E, Kiany-Borazjani M
(2000) Synth Commun 30:2057
ˆ
Parvulescu VI, Hardacre C (2007) J Mol Catal A Chem 269:64
7. Tajik H, Niknam K, Parsa F (2009) J Iran Chem Soc 6:159
8. Bhosale RS, Sarda SR, Giram RP, Raut DS, Parwe SP, Ardhapure
SS, Pawar RP (2009) J Iran Chem Soc 6:519
26. Zolfigol MA, Shirini F, Ghorbani Choghamarani A, Taqiannasab
A, Keypour H, Salehzadeh S (2000) J Chem Res (S) 420
27. Zolfigol MA, Zebarjadian MH, Chehardoli G, Keypour H,
Salehzadeh S, Shamsipur M (2001) J Org Chem 66:3619
28. Zolfigol MA, Shirini F, Choghamarani AG (2002) Synth Com-
mun 32:1809
29. Zarchi MAK, Noei J (2009) J Appl Polym Sci 114:2134
30. Roche D, Lardy C, Tournier L, Prunier M, Valeur E (2010)
Tetrahedron Lett 51:2277
9. Hajipour AR, Rafiee F, Ruoho AE (2010) J Iran Chem Soc 7:114
10. Valizadeh H, Shockravi A (2009) Heteroatom Chem 20:284
11. Valizadeh H, Gholipour H (2010) Synth Commun 40:1477
12. Valizadeh H (2010) Heteroatom Chem 21:78
13. Valizadeh H, Shockravi A (2009) Synth Commun 39:4341
14. Garcia-Rio L, Leis JR, Issglesias E (1997) J Org Chem 62:4712
15. Nudelman NS, Bonatti AE (2000) Synlett 1825 (references cited
therein)
31. Valizadeh H, Shomali A (2010) Dyes Pigm. doi:10.1016/
j.dyepig.2010.11.010
16. Vogel AI, Tatchell AR, Furnis BS, Hannaford AJ, Smith PWG
(1986) Vogels text book of practical organic chemistry, 4th edn.
Longman, London
32. Hou J-Y, Wang Y-L, Wang J-Y (2003) J Chem Res (S) 626
33. Smith JRL, Nee MW, Noar JB, Bruice TC (1984) J Chem Soc
Perkin Trans 2 255
17. Olah GA (1979) Aldrichimica Acta 12:43
34. Iranpoor N, Firouzabadi H, Nowrouzi N (2008) Tetrahedron Lett
49:4242
35. Seebach D, Enders D (1975) Chem Ber 108:1293
36. Loeppky RN, Elomari S (2000) J Org Chem 65:96
37. Gowenlock BG, Pfab J, Young VM (1997) J Chem Soc Perkin
Trans 2 915
18. Lecher H, Siefhen W (1926) Chem Ber 59:2594
19. Makhora NN, Karpov GA, Mikhailyuk AN, Bova AE,
Khmel’nitskii LI, Novikov SS (1978) lzv Akad Nauk SSSR Ser
Khim 1:226
20. Chang SK, Harrington GW, Rothstein M, Shergalis WA, Swern
D, Vohra SK (1979) Cancer Res 39:3871
38. Giumanini AG, Verardo G (1997) Can J Chem 75:469
39. Yu Y, Ostresh JM, Houghten RA (2003) J Org Chem 68:183
´
21. Castedo L, Riguera R, Vazquez MP (1983) J Chem Soc Chem
Commun 301
123