Amine exchange reactions in ionic liquid

Article abstract of DOI:10.1080/10426500802339865

An operationally simple, inexpensive, efficient, and environmentally friendly protocol for the amine exchange reactions of 3-N,N- dimethylaminopropiophenone and N,N-dimethylaminomethylferrocene with primary aryl amines is developed using the ionic liquid

Full text of DOI:10.1080/10426500802339865

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Phosphorus, Sulfur, and Silicon
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Amine Exchange Reactions in
Ionic Liquid
Gajanan Rashinkar a , Santoshkumar Pore a
Rajeshree Salunkhe a
&
a Department of Chemistry , Shivaji University ,
Kolhapur, India
Published online: 22 Jun 2009.
To cite this article: Gajanan Rashinkar , Santoshkumar Pore & Rajeshree Salunkhe
(2009) Amine Exchange Reactions in Ionic Liquid, Phosphorus, Sulfur, and Silicon and
the Related Elements, 184:7, 1750-1758, DOI: 10.1080/10426500802339865
To link to this article: http://dx.doi.org/10.1080/10426500802339865
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Phosphorus, Sulfur, and Silicon, 184:1750–1758, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802339865
Amine Exchange Reactions in Ionic Liquid
Gajanan Rashinkar, Santoshkumar Pore,
and Rajeshree Salunkhe
Department of Chemistry, Shivaji University, Kolhapur, India
An operationally simple, inexpensive, efficient, and environmentally friendly pro-
tocol for the amine exchange reactions of 3-N,N-dimethylaminopropiophenone and
N,N-dimethylaminomethylferrocene with primary aryl amines is developed using
the ionic liquid [bmim]PF as a solvent. The recovered ionic liquid can be reused
6
for several cycles with constant activity.
Keywords Amine exchange reactions; 1-butyl-3-methyl imidazolium hexafluorophos-
phate; Mannich bases
INTRODUCTION
Secondary alkyl amines in general are commonly employed for
aminomethylation reactions following the early work of Carl Man-
nich. More recent investigations of the aminomethylation reaction
have substantiated that less common alkyl amines,1 amino acids,2 or
phthalimide3 can be used effectively as amine components in the clas-
sical Mannich reaction. Until the mid-1970s, aryl amines were spo-
radically reported to react with various functionalities like phenols4
and heterocyclic compounds.5,6 More recently, arylaminomethylation
of acetophenones has been studied extensively by the addition to a
Schiff base generated in situ.7–9 The amine exchange reaction, which
consists of the interaction between an alkyl amine Mannich base and
an aryl amine as reported by Singh and Singh,10 also provides a route
to aryl amine Mannich bases.
With green chemistry becoming a central issue in the 21st cen-
tury, much effort has been made on reducing, recycling, or eliminating
Received 2 January 2008; accepted 12 July 2008.
Address correspondence to Rajeshree Salunkhe, Department of Chemistry, Shivaji
University, Kolhapur–416004, (MS) India. E-mail: gsrchemsuk@yahoo.co.in
1750

Amine Exchange Reactions
1751
+
N
N
PF6
FIGURE 1 [bmim] PF6.
the use of toxic chemicals in synthetic chemistry. An intriguing line
of inquiry in green chemistry is the use of room temperature ionic
liquids (RTILs) for organic reactions instead of traditional solvents.
The tempting properties of RTILs such as negligible vapor pressure,
large liquidus range, high thermal stability, large electrochemical win-
dow, and the ability to solvate compounds of varying polarity have
made them an environmentally friendly reaction medium for organic
synthesis.11
Here we report an operationally simple, inexpensive, efficient, and
ecofriendly protocol for the amine exchange reaction in an ionic liquid,
1-butyl-3-methyl imidazolium hexafluorophosphate [bmim]PF6 (Fig-
ure 1), as a solvent.
RESULTS AND DISCUSSION
We first focused on the amine exchange reaction between 3-N,N-
dimethylaminopropiophenone 1 and aniline. Since mixtures of prod-
ucts usually are obtained in amine exchange reactions, the outcome
of this reaction was of particular interest. The reaction proceeded
smoothly in [bmim]PF6 at room temperature yielding the expected
β-anilinopropiophenone 3a in 92% yield without any side products.
Subsequently, the reaction of compound 1 with a variety of aryl amines
2a–h was investigated (Scheme 1). In most cases, respective products
were obtained in good to excellent yields (Table I).
O
O
Me
[bmim] PF
6
NHAr
+
N
Ar - NH
2
RT
Me
3a-h
2a-h
1
SCHEME 1

1752

1753

1754
G. Rashinkar et al.
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
78%
58%
39%
24%
12%
RT
30
40
50
60
Te mpe rature (°C)
FIGURE 2 Amine exchange reaction of N,N-dimethylaminomethylferrocene
with aniline in [bmim]PF6 at different temperatures. Reactions were performed
for 48 h. aIsolatedyields.
In order to check the general applicability of this protocol, we reacted
N,N-dimethylaminomethylferrocene 4 with aryl amines in [bmim]PF6.
Preliminary investigations carried out at room temperature did not
yield quantitative results. The reaction between 4 and aniline was
performed at different temperatures. The best results were obtained
◦
when the reaction was carried out at 60 C (Figure 2). Using the opti-
mized experimental conditions, we checked the feasibility of the method
by reacting 4 with the aryl amines 2a–e (Scheme 2). The results are
summarized in Table II and confirm the general applicability of the
protocol.
Me
[bmim] PF
6
H - Ar
N
N
+
2a-e
60 °C
Me
Fe
Fe
5a-e
4
SCHEME 2
For arylamines, the effect of steric demand on the yield appeared
to be of greater importance than electronic effects. For instance, the
reaction of 1 with p-substituted anilines showed comparable results,

Amine Exchange Reactions
1755
TABLE II Amine Exchange Reactions of
N,N-Dimethylaminomethylferrocene with Aryl Amines in [bmim]PF6a
Productb (5)
Time (h)
48
Yieldc (%)
78
Mpd (◦C)
a
b
c
d
e
83–85
(82–84)13
46
49
40
38
77
79
73
80
126–128
(126–128)13
48–50
(50–52)13
63–64
(62–64)13
123–125
(124–126)13
Fc = C5H5FeC5H4
aReactions were carried out at 60◦C.
bAll products were characterized by 1H NMR and IR spectroscopy as well as by
mass spectrometry.
cIsolated yields.
dLiterature values in parenthesis.
while the sterically hindered 2-naphthylamine afforded a lower yield
of the respective product.
We observed that [bmim]PF6 recovered after the reaction can be
recycled and reused without any significant loss in chemical yield
of the products. The use of recycled [bmim]PF6 was investigated
by the reaction of 1 with aniline. High yields were obtained un-
til the fourth regeneration of [bmim]PF6. The results are shown in
Figure 3.
It is noteworthy to mention that the above method provides
an alternative ecofriendly and economical route for the synthe-
sis of N-arylaminomethylferrocenes, which are otherwise obtained
by NaBH4/LiAlH4 reduction of ferrocenylaldimines, resulting from
the reaction between ferrocenecarboxyaldehyde and aryl amines
(Scheme 3).13

1756
G. Rashinkar et al.
NH 2
O
O
[bmim] PF
RT
6
Me
Me
NH
N
+
92
92
90
88
86
84
82
80
78
76
74
86
84
83
80
0
1
2
Regeneration
3
4
FIGURE 3 Use of recycled [bmim]PF6. Reactions were performed at room
temperature for 24 h. aIsolated yields.
ArNH2
LiAlH4 / NaBH4
Fc-CHO
Fc- CH=N-Ar
Fc-CH2-NMe2
Fc-CH2-NH-Ar
ArNH2
[bmim] PF6
SCHEME 3 Synthesis of N-arylaminomethylferrocenes.
CONCLUSION
We have developed an operationally simple, efficient, and ecofriendly
methodology for amine exchange reactions in the ionic liquid
[bmim]PF6. The proposed method is quite general and works with di-
verse aryl amines. The mild conditions and high yields of the products
not only make this protocol an alternative route to the conventional
methods, but it also becomes significant under the umbrella of environ-
mentally greener and safer processes.

Amine Exchange Reactions
1757
EXPERIMENTAL
Melting points were determined in an open capillary and are uncor-
rected. IR spectra were recorded on Perkin-Elmer Spectrum One FTIR
1
spectrophotometer using KBr pellets. H NMR spectra were recorded
with a Varian Mercury YH-300 instrument using CDCl3 as solvent and
TMS as internal reference. Mass spectra were recorded with a Shi-
madzu QP2010 GCMS with an ion source temperature of 200◦C.
The ionic liquid [bmim]PF6,14 3-N,N-dimethylaminopropiop-
henone,15 and N,N-dimethylaminomethylferrocene16 were synthesized
following procedures reported in the literature. All other chemicals
were obtained from commercial suppliers and used without further
purification.
Amine Exchange in [bmim]PF6: General Procedure
A mixture of 3-N,N-dimethylaminopropiophenone (1 mmol) or N,N-
dimethylamino-methylferrocene (1 mmol) and the aryl amine (1 mmol)
in 1 mL of [bmim]PF6 was stirred at the appropriate temperature
(Tables I and II). After completion of the reaction, as indicated by TLC,
the resulting mixture was extracted from the ionic liquid phase using
Et2O (3 × 10.0 mL). Evaporation of the organic solvent afforded the
crude product, which was purified by column chromatography on silica
gel using petroleum ether (60–80 ◦C):ethyl acetate (9:1).
Spectral Data of Representative Compounds
1-Phenyl-3-phenylamino-propan-1-one (3a)
White solid; IR (KBr) (υmax,cm1): 3408 (N-H), 1677 (C=O); 1H-NMR
(300 MHz, CDCl3): δ = 3.28 (t, 2H, CH2-N), 3.60 (t, 2H, CH2-CO), 4.11
(bs, 1H, NH), 6.61 (m, 3H, arom-H) 7.18 (m, 3H, arom-H), 7.42 (d, 2H,
arom-H), 7.89 (d, 2H, arom-H); MS (EI): m/z - 225 (M+).
3(4ꢀ-chlorophenylamino)-1-phenylpropan-1-one (3b)
1
White solid; IR(KBr) (υmax,cm1): 3394 (N-H), 1670 (C=O); H-NMR
(300 MHz, CDCl3): δ = 3.27 (t, 2H, CH2-N), 3.57 (t, 2H, CH2-CO), 4.12
(bs, 1H, NH), 6.60 (d, JHH = 8.4 Hz, 2H, arom-H) 7.12 (m, 3H, arom-H),
7.38 (d, 2H, arom-H), 7.91 (d, JHH = 8.2 Hz, 2H, arom-H). MS (EI) : m/z
- 259 (M+).
(N-p-Chlorophenyl)aminomethylferrocene (5b)
1
Yellow solid; IR(KBr) (υmax,cm1): 3421 (N-H); H-NMR (300 MHz,
CDCl3): δ = 3.92 (s, 2H, Fc-CH2), 4.10 (bs, 1H, NH), 4.15 (s, 2H, Fc),

1758
G. Rashinkar et al.
4.17 (s, 5H, Fc), 4.22 (s, 2H, Fc), 6.56 (d, JHH = 8.4 Hz, 2H, arom-H),
7.12 (d, JHH = 8.1 Hz, 2H, arom-H); MS (EI): m/z - 326 (M+).
(N-p-Nitrophenyl)aminomethylferrocene (5e)
Yellow solid; IR(KBr) (υmax,cm1): 3409 (N-H), 1519 (NO2)asym, 1340
(NO2)sym; 1H-NMR (300 MHz, CDCl3): δ = 4.02 (s, 2H, Fc-CH2-N), 4.09
(bs, 1H, NH), 4.12 (s, 2H, Fc), 4.27 (s, 5H, Fc), 4.68 (s, 2H, Fc), 7.23 (d,
JHH = 8.8 Hz, 2H, arom-H), 8.08 (d, JHH = 8.8 Hz, 2H, arom-H); MS
(EI): m/z - 337 (M+).
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