Nafion-Fe: A new efficient "green" lewis acid catalyst for the ketonic strecker reaction

Article abstract of DOI:10.1007/s10562-012-0958-2

The synthesis of various α-aminonitriles, precursors of α-amino acids has been carried out in moderate to high yields and high purity by the Strecker reaction from ketones, aliphatic/aromatic amines and TMSCN using a new "green" Lewis acid catalyst, Nafion-Fe (iron Nafionate, Fe(III) salt of Nafion-H, a solid polymeric perfluoroalkanesulfonic acid) under conventional thermal as well as microwave conditions. Microwave and solvent-free conditions applied in this method shorten the reaction times, improve the yields and diminishes the formation of side products. Strecker reaction occurs smoothly with secondary aliphatic amines also under these conditions which is not common under conventional conditions.

Full text of DOI:10.1007/s10562-012-0958-2

Catal Lett (2013) 143:303–312
DOI 10.1007/s10562-012-0958-2
Nafion–Fe: A New Efficient ‘‘Green’’ Lewis Acid Catalyst
for the Ketonic Strecker Reaction
•
G. K. Surya Prakash Inessa Bychinskaya
•
•
Eric R. Marinez Thomas Mathew
•
George A. Olah
Received: 13 December 2012 / Accepted: 24 December 2012 / Published online: 31 January 2013
Ó Springer Science+Business Media New York 2013
Abstract The synthesis of various a-aminonitriles, pre-
cursors of a-amino acids has been carried out in moderate
to high yields and high purity by the Strecker reaction from
ketones, aliphatic/aromatic amines and TMSCN using a
new ‘‘green’’ Lewis acid catalyst, Nafion–Fe (iron Nafio-
nate, Fe(III) salt of Nafion–H, a solid polymeric perfluo-
roalkanesulfonic acid) under conventional thermal as well
as microwave conditions. Microwave and solvent-free
conditions applied in this method shorten the reaction
times, improve the yields and diminishes the formation of
side products. Strecker reaction occurs smoothly with
secondary aliphatic amines also under these conditions
which is not common under conventional conditions.
It is a multicomponent reaction (MCR) involving three
substrates: an aldehyde or ketone, an amine and a cyanide
reagent. Historically, it is the first example of a MCR [2].
With the increasing demand for sustainable chemistry, MCR
became prominent in organic synthesis [3–8].
The Strecker reaction of aldehydes is very common and
occurs smoothly in the presence of various types of cata-
lysts [9–18]. After the development of an efficient protocol
for ketonic Strecker reaction utilizing Ga(OTf)3 as the
catalyst in our group [18], reports started to appear on
Strecker reaction of ketones with anilines [19–21] and with
benzylamines [22] under mild conditions. However, there
are not many reports on the direct Strecker reaction of
ketones with primary and secondary aliphatic amines.
Generally Strecker synthesis using ketones is performed
step-wise [19–21, 23–26] or under high pressure [27, 28].
Increasingly, green chemistry based protocols have become
crucial in sustainable development [29–31]. Therefore,
finding a suitable environmentally benign heterogeneous
solid acid catalyst, which can be easily separated and
recycled, is highly desirable [32–36]. Solid acids, such as
clays, ion-exchange resins and zeolites are extensively
applied in organic synthesis [34]. They have been proved to
be cost-effective, environmentally benign, and facilitate the
reaction process with ease.
Keywords Nafion–Fe Á Strecker reaction Á
a-Aminonitriles Á Sustainable development Á
Microwave irradiation
1 Introduction
The Strecker reaction is a powerful chemical tool for the
synthesis of a-aminonitriles, precursors of a-aminoacids [1].
G. K. Surya Prakash (&) Á I. Bychinskaya Á T. Mathew (&) Á
G. A. Olah
Encouraged by our previous results in Strecker synthesis
employing solid Brønsted acid catalyst Nafion–H [37], and
the successful application of mercury(II), chromium(III)
and cerium(IV) impregnated Nafion–H in various organic
transformations (hydration, nitration, oxidation) [38], we
decided to prepare various metal salts of Nafion–H (metal
Nafionates) by metal exchange using Nafion–K and cor-
responding metal halides. As one among them, iron(III)
Nafionate (Nafion–Fe) was prepared and its catalytic effi-
cacy has been investigated for the Strecker reaction.
Department of Chemistry, Loker Hydrocarbon Research
Institute, University of Southern California, Los Angeles,
CA 90089-1161, USA
e-mail: gprakash@usc.edu
T. Mathew
e-mail: tmathew@usc.edu
E. R. Marinez
Department of Chemistry and Biochemistry, California State
University, Long Beach, 1250 Bellflower Boulevard,
Long Beach, CA 90840-950, USA
123

304
G. K. Surya Prakash et al.
series of novel protocols for various organic transforma-
tions utilizing iron salts have appeared in the last few years
[40]. Due to such distinct characteristics, the new catalyst
is expected to find wide applications in the field of green
chemistry and make significant contribution in satisfying
the requirements for sustainable synthesis.
CF
O
(CF2 CF2) x
CF2
y
K
(CF2
CF2
SO3
CF O) m
CF3
CF2
CH2Cl2
FeBr3
(CF2
CF CF2
CF2) x
y
2 Results and Discussion
Fe
SO3
O
(CF2 CF
CF2 CF2
O) m
We have probed the catalytic potential of Nafion–Fe by
performing the Strecker reaction with various aldehydes and
ketones with aniline and TMSCN for the formation of
a-aminonitriles. Initially the reaction was carried out with
benzaldehyde derivatives at 60 °C in dichloromethane
(Scheme 2). The reactions were found to be very clean and
after the reactions, the purification of the products were
achieved by simple trituration with hexanes giving the
products in good to excellent yields in high purity (Table 1).
Based on our previous experience [18], CH2Cl2 was cho-
sen as the most suitable and efficient solvent due to its min-
imum interaction with catalyst as well as the substrates unlike
toluene or acetonitrile. The reactions proceeded smoothly and
clean products were obtained in almost all cases.
CF3
3
Nafion-Fe Solid Resin
Scheme 1 Preparation of Nafion–Fe
Nafion–Fe was prepared from finely powdered Nafion–K
by simple cation exchange reaction with FeBr3 in CH2Cl2
(Scheme 1).
The exchange of potassium to iron was confirmed using
elemental analysis. The data showed a high degree of
exchange, leaving only a minimal amount of potassium.
The morphology of the catalyst was preserved during its
preparational procedures as manifested by the comparison
of SEM images of the original Nafion–K and Nafion–Fe
samples (Fig. 1). Elemental analysis of Nafion–Fe shows
the incorporation of 2.9 % of Fe.
Next, we tested the recyclability of Nafion–Fe. The
catalyst was found to be very stable and recyclable. After
each run, the catalysts was filtered off and washed few
times with CH2Cl2 and dried. The sample was reused for
seven consecutive times and in all cases, 100 % conversion
was observed showing that the catalytic efficacy remains
almost unchanged (Scheme 3). However, the elemental
analysis of the catalyst after seven cycles showed that a
partial leaching of the metal content possibly by hydrolysis
of the catalyst to Nafion–H.
Fe(III) salt of Nafion–H, can be considered as the Lewis
acid version of the corresponding Brønsted acid Nafion–H,
and possesses all advantageous properties of Nafion–H. It
is highly active, non-toxic, thermally and aqueous stable,
easily accessible, and environmentally friendly. Low cat-
alyst loading is required for the reactions and the catalyst
can be recycled. Iron(III) is a strong and hard Lewis acid
and can serve as a potent catalyst for the carbonyl group
activation [39]. Besides that, iron is the most abundant
transition metal in the nature, making it easily accessible
with low cost, low toxicity, environmentally friendly
character and sustainability. As a result, the chemist’s
attention towards iron-catalysis is constantly growing and a
After developing the successful ketonic Strecker reaction
protocol using Ga(OTf)3 as catalyst [18, 41], we were in
search of other convenient and easily recyclable Lewis acid
systems. Results from the Nafion–Fe catalyzed Strecker
reaction with aldehydes prompted us to screen various
Fig. 1 a SEM image of
Nafion–K beads and b Nafion–
Fe prepared from Nafion–K
123

Nafion–Fe catalyzed Strecker reaction
305
Scheme 2 Nafion–Fe catalyzed
Strecker reaction of
benzaldehydes
NH2
CHO
CN
Nafion-Fe
N
R
+
+
TMSCN
R
H
CH2Cl2, 60 oC, 4 h
Table 1 Nafion–Fe catalyzed
Strecker reactions using
benzaldehydes and aniline
Entry
1
Aldehyde
Product
CN
Yield (%)
95
CHO
CHO
N
H
CN
N
H
2
3
4
5
90
88
85
82
Cl
Cl
Br
CN
CHO
CHO
N
H
Br
CN
N
H
O2N
O2N
CN
CHO
CHO
N
H
NC
NC
CN
N
H
6
63
F
F
Scheme 3 Recylability of
Nafion–Fe
CN
CHO
NH2
+
Nafion-Fe
CH2Cl2, 60 oC, 4 h
N
H
+
TMSCN
2
Run
3
4
5
7
6
1
Conversion of
aldehde (%)
100
100
100
100
100
100
100
123

306
G. K. Surya Prakash et al.
Scheme 4 Nafion–Fe catalyzed
Strecker reaction of various
ketones with amines
O
CN
Nafion-Fe
+ R2-NH2
TMS-CN
+
R1
R
R1
CH2Cl2, 80 oC, 6 h
N
R
R1
H
Table 2 Nafion–Fe catalyzed
Strecker reaction using ketones
and aniline
Entry
1
Yield (%
88a
Ketone
O
Product
CN
H3C
N
H
H3C
CH3
H3C
CN
O
H3C
2
3
4
90
N
H
C2H5
C2H5
H3C
CH3
CN
O
O
FH2C
96b
90
N
H
CH2F
H3C
CN
N
H
O
O
CN
H3C
5
62
CH3
N
H
CN
C2H5
6
7
57
70
N
H
C2H5
O
H3C
CN
CH3
N
H
CN
O
N
H
a
8
67
At 60 °C
at room temperature
b
ketones for the challenging ketonic Strecker reaction with
different amines in the presence of Nafion–Fe keeping
TMSCN as cyanide source (Scheme 4). The ketonic Strec-
ker reactions were initially conducted with aniline as the
amine. Though the reactions required higher temperature
and prolonged reaction time, the expected products were
obtained in good yields with many substrates (Table 2).
Steric as well as electronic factors play a significant role
in this reaction. In the case of propiophenone, the yield was
found to be moderate, while a significant increase in yield
was observed when phenylacetone was used (Table 2,
entries 6, 7). In the case of a-tetralone, due to steric factor
resulting from the close proximity of the fused benzene
ring and ring hydrogen, the desired product was not
observed even at higher temperature and prolonged reac-
tion times (100 °C for 24 h). However, b-tetralone
(Table 2, entry 8) reacted smoothly under the regular
conditions. Encouraged by the results from the reaction of
aliphatic ketones, especially 2-butanone and aniline
(Table 2, entry 2), we checked the feasibility and catalytic
potential of Nafion–Fe in the reactions of 2-butanone with
various amines and also found them efficient (Table 3).
As mentioned in our previous studies [37], the Strecker
reaction of ketones and aliphatic amines under conventional
conditions led to mixtures with considerable drop in selec-
tivity towards the desired product. In order to further increase
the yields and to reduce reaction times, a few experiments
were carried out under microwave irradiation. Indeed, it was
123

Nafion–Fe catalyzed Strecker reaction
307
Table 3 Nafion–Fe catalyzed
Strecker reaction of 2-butanone
and amines
Product
Entry
1
Amine
Yield (%)
H
N
CN
C2H5
NH2
90
CH3
CH3
H
N
NH2
CH3
CN
2
C2H5
CH3
68
H
CN
C2H5
CH3
N
NH2
NH2
80
70
3
4
O2N
O2N
H
N
CN
C2H5
CH3
H3CO
H3CO
H
N
NH2
CN
C2H5
CH3
5
6
72
Cl
Cl
CN
C2H5
20a
NH
N
N
CH3
CN
C2H5
39a
7
NH
a
1
Crude yield, calculated by H
NMR
CH3
found that yields enhanced significantly (Table 4, entries
1–9). The Strecker reactions of 2-butanone with aliphatic as
well as aromatic amines under microwave conditions pro-
ceeded smoothly with high yields of the products.
pyrrolidine can be conveniently carried out in one-pot fashion
leading to pharmaceutically useful intermediates.
For a better comparison of the catalytic potential and
efficacy of Nafion–Fe with other catalysts including the
Ga(OTf)3 and Nafion–Ga (another efficient Lewis acid
version of Nafion–H) Strecker reaction of cyclohexanone
with morpholine and TMSCN was studied (Table 5) under
microwave conditions. Nafion–Fe was found to be the most
efficient catalyst in this particular case.
In many cases, we found that the yield of the desired
products was improved significantly (Table 4, entries 3, 4).
ThecitedexampleshighlightthecatalyticpotentialofNafion–
Fe under microwave irradiation. In addition to significant
yield enhancement, the use of microwave irradiation and
solvent-free conditions allowed us to reduce reaction times
substantially. In the case of ketones, reactions are completed
in 1–2 h, whereas under conventional conditions it took 6 h to
achieve similar results. In case of aldehydes, reactions are
completed in 7 min, while under regular conditions they
require 4 h. In a blank reaction (without the catalyst) full
conversion was not achieved, even under prolonged micro-
wave irradiation. In most cases under Nafion–Fe catalysis the
reactions turned out to be very clean, even the crude products
were found to be analytically pure in many cases. One of the
significant aspects of this methodology is that the Strecker
synthesis using various ketones and morpholine as well as
3 Experimental
3.1 General
The aldehydes, ketones, amines, and NafionÒ SAC-13 were
purchased from Sigma-Aldrich (Milwaukee, WI). Nafion-
Fe was prepared from NafionÒ–K (potassium salt). The
fluorinated ketones and TMSCN were purchased from
other commercial sources. The solvent used in all three-
component reactions was dichloromethane (CH2Cl2).
123

308
G. K. Surya Prakash et al.
Table 4 Microwave irradiation
assisted Strecker reaction
catalyzed by Nafion–Fe
Amine
Entry Ketone/Aldehyde
Product
CN
Yield (%)
97 (90)a
O
NH2
1
H3C
C2H5
N
H3C
H3C
C2H5
C2H5
H
CN
O
NH2
CH3
77 (68)
H3C
C2H5
2
N
H
CH3
CN
O
O
H3C
C2H5
3
4
47 (20)b
N
H3C
H3C
C2H5
C2H5
N
H
CN
NH
56 (39)b
80 (67)
H3C
C2H5
N
O
CN
NH2
NH2
5
N
H
O
CN
C2H5
78 (57)
6
7
N
H
C2H5
CN
O
CHO
49 (37)b
N
N
H
O
CN
CHO
NH2
NH2
N
H
87 (63)c
8
F
F
CN
CHO
N
96 (82)c
9
H
NC
NC
O
C2H5
O
CN
72
C2H5
N
10
N
H
O
O
CN
O
N
O
76
85
a
Values in parentheses are
yields under conventional
conditions
11
12
N
H
O
b
CN
Crude yields, calculated by
1H NMR
c
NH
N
Reaction time 7 min.
Control experiment was conducted using Ga(OTf)3 as the
catalyst for comparison.
1H, 13C and 19F NMR spectra were recorded on Varian
NMR spectrometers at 400 MHz. 1H NMR chemical shifts
were determined relative to internal tetramethylsilane at d
0.0 or to the signal of residual CHCl3 in CDCl3 (d 7.26),
13C NMR chemical shifts were determined relative to tet-
ramethylsilane at d 0.0 or to the 13C signal of CDCl3 at d
77.0. 19F NMR chemical shifts were determined relative to
CFCl3 at d 0.0. Biotage Initiator 1 was used for microwave
irradiation. Elemental analysis data for Nafion–Fe were
obtained from Galbraith Laboratories Inc. The surface
123

Nafion–Fe catalyzed Strecker reaction
309
mixture was then filtered, the solid residue (catalyst) was
washed with CH2Cl2 (3 9 15 mL) and retained for recy-
cling. The filtrate was collected and the solvent was
removed under reduced pressure to obtain the product.
Further purification (if necessary) can be carried out by
trituration of the residue with excess hexanes followed by
evaporation of hexanes.
Table 5 Comparison of the catalytic activity of various catalysts in
the Strecker synthesis
O
CN
O
catalyst
N
+
+
TMSCN
O
neat, MW, 100 oC, 1h
N
H
Entry
Catalyst
Yield (%)
3.4 The Strecker synthesis using microwave irradiation
1
2
3
4
5
6
a
Nafion–Fe
Nafion–H
76
35
46
10a
42
51
To a microwave vial containing Nafion–Fe (100 mg),
1 mmol of ketone and 1 mmol of an amine (1.2 mmol in the
case of pyrrolidine) were added and stirred. To the mixture,
TMSCN (0.2 mL, 1.6 mmol) was then added, the vial was
sealed, placed in a microwave and heated for 1 h (2 h in the
case of propiophenone with cyclopentylamine, 2-butanone
with pyrrolidine) at 100 °C. The catalyst was filtered off the
reaction mixture, washed with CH2Cl2 and retained for
recycling. The filtrate was collected and the solvent was
removed under reduced pressure. In most cases the products
were obtained in analytically pure form. When excess of
amine was used, an aqueous work-up was performed.
Nafion–H/molecular sieves
Molecular sieves
Nafion–Ga
Ga(OTf)3
Conversion, side products were also observed
morphology of the catalysts was studied by means of
scanning electron microscopy (SEM) at the Center for
Electron Microscope and Microanalysis at University of
Southern California. High resolution mass spectra were
recorded in ESI mode on a high resolution mass spec-
trometer at the Mass Spectrometry facility, University of
Arizona.
3.5 Spectral Data
3.2 Preparation of Nafion–Fe from NafionÒ–K
3.5.1 2-Phenyl-2-(phenylamino)acetonitrile (Table 1,
entry 1 [20, 27, 37, 41])
In a 250 mL round-bottomed flask, 5 g of NafionÒ–K
powder (\250 lm) and 5 g of anhydrous FeBr3 were
placed, 150 mL of 1,2-dichloroethane was then added and
the mixture was kept under reflux for 48 h. After cooling
the mixture to room temperature, the resulting solids were
filtered using a Bu¨chner funnel, washed with fresh portion
of 1,2-dichloroethane (2 9 25 mL) and then with deion-
ized water in portions (*300 mL in total) to remove
excess of FeBr3 till the filtrate turned colorless and neutral
(checked with pH paper). The catalyst further was washed
with acetone (reagent grade, 100 mL) to remove remaining
water, transferred to a 50 mL round-bottomed flask and
dried at room temperature for 16 h under vacuum using a
P2O5 trap. Nafion–Fe(III) was obtained as a light brown
powder (5.15 g).
1H NMR (400 MHz, CDCl3): d 3.85 (brs, 1H, NH), 5.16 (s,
1H), 6.52 (d, J = 7.9 Hz, 2H), 6.66 (t, J = 7.4 Hz, 1H),
7.03 (t, J = 7.9 Hz, 2H), 7.16–7.22 (m, 3H), 7.33–7.35 (m,
2H); 13C NMR (100.6 MHz, CDCl3): d 50.2, 114.2, 118.3,
120.3, 127.3, 129.4, 129.5, 129.6, 134.0, 144.7.
3.5.2 2-(4-Chlorophenyl)-2-(phenylamino)acetonitrile
(Table 1, entry 2 [37, 42])
1H NMR (400 MHz, CDCl3): d 4.03 (d, J = 8.5 Hz, 1H,
NH), 5.42 (d, J = 8.5 Hz, 1H), 6.77 (d, J = 7.9 Hz, 2H),
6.92 (t, J = 7.3 Hz, 1H), 7.28 (m, 2H), 7.44 (d,
J = 8.5 Hz, 2H), 7.55 (d, J = 8.5 Hz, 2H). 13C NMR
(100.6 MHz, CDCl3): d 49.6, 114.3, 117.8, 120.6, 128.6,
129.5, 129.6, 132.4, 135.9, 144.3.
3.3 General Method for the Nafion–Fe(III) Catalyzed
Strecker Reactions of Aldehydes and Ketones
3.5.3 2-(4-Bromophenyl)-2-(phenylamino)acetonitrile
(Table 1, entry 3 [37, 42])
A mixture of aldehyde or ketone (1 mmol of acetone,
1.5 mmol in the case of 2-butanone) and amine (1 mmol)
dissolved in CH2Cl2 (4 mL) was added to Nafion–Fe
(100 mg) in a pressure tube with a magnetic stir bar.
TMSCN (0.3 mL, 2.4 mmol) was added and the pressure
tube was closed. The mixture was stirred at 60 °C for 4 h
(for aldehydes) or at 80 °C for 6 h (for ketones). The
1H NMR (400 MHz, CDCl3): d 4.02 (brs, 1H, NH), 5.39
(d, J = 8.5 Hz, 1H), 6.75 (m, 2H), 6.88–6.93 (m, 1H),
7.24–7.29 (m, 2H), 7.41–7.49 (m, 2H), 7.52–7.60 (m, 2H);
13C NMR (100.6 MHz, CDCl3): d 49.7, 114.3, 117.7,
120.6, 123.7, 128.9, 129.6, 132.5, 133.0, 144.3.
123

310
G. K. Surya Prakash et al.
2
1
3.5.4 2-(4-Nitrophenyl)-2-(phenylamino)acetonitrile
(Table 1, entry 4 [18])
(d, JCF = 20.5 Hz), 85.2 (d, JCF = 185.1 Hz), 119.0 (d,
3JCF = 3.7 Hz), 119.1, 122.3, 129.6, 142.8. 19F NMR
1
(376.4 MHz, CDCl3): d -223.1 (t, JFH = 46.6 Hz).
1H NMR (400 MHz, CDCl3): d 4.09 (d, 1H, NH), 5.51 (d,
J = 8.9 Hz, 1H), 6.70 (d J = 7.9 Hz, 2H), 6.88 (t,
J = 7.7 Hz, 1H), 7.19–7.24 (m, 3H), 7.76–7.78 (m, 2H),
8.24–8.27 (m, 2H); 13C NMR (100.6 MHz, CDCl3): d 49.9,
114.7, 117.3, 121.3, 124.6, 128.4, 129.9, 140.8, 144.0, 148.7.
3.5.10 1-(Phenylamino)cyclohexanecarbonitrile
(Table 2, entry 4 [18, 20])
1H NMR (400 MHz, CDCl3): d 1.12–1.15 (m, 1H),
1.45–1.60 (m, 7H), 2.15–2.18 (m, 2H), 3.6 (brs, 1H, NH),
6.69–6.77 (m, 3H), 7.03–7.11 (m, 2H); 13C NMR
(100.6 MHz, CDCl3): d 22.2, 24.9, 36.6, 54.3, 117.4,
120.4, 121.2, 129.2, 143.6.
3.5.5 2-(4-Cyanophenyl)-2-(phenylamino)acetonitrile
(Table 1, entry 5 [43])
1H NMR (400 MHz, CDCl3): d 4.10 (d, J = 8.7 Hz, 1H,
NH), 5.47 (d, J = 8.7 Hz, 1H), 6.69 (d, J = 8.1 Hz, 2H),
6.87 (t, J = 7.2 Hz, 1H), 7.21(t, J = 8.1 Hz, 2H), 7.61–7.73
(m, 4H); 13C NMR (100.6 MHz, CDCl3): d 57.1, 115.7,
119.9, 120.7, 124.8, 128.6, 129.0, 129.2, 139.8, 143.4.
3.5.11 2-Phenyl-2-(phenylamino)propionitrile
(Table 2, entry 5 [18, 20])
1H NMR (400 MHz, CDCl3): d 1.93 (s, 3H), 4.20 (s, 1H,
NH), 6.46 (d, J = 7.7 Hz, 2H), 6.73 (t, J = 7.3 Hz, 1H),
7.04 (t, J = 7.2 Hz, 2H), 7.27–7.35 (m, 3H), 7.54–7.56 (m,
2H); 13C NMR (100.6 MHz, CDCl3): d 33.4, 57.1, 115.7,
119.9, 120.7, 124.8, 128.6, 129.0, 129.2, 139.8, 143.4.
3.5.6 2-(3-Fluorophenyl)-2-(phenylamino)acetonitrile
(Table 1, entry 6 [44])
1H NMR (400 MHz, CDCl3): d 4.06 (brs, 1H, NH), 5.38
(s, 1H), 6.70 (d, J = 7.7 Hz, 2H), 6.85, (t, J = 7.7 Hz, 1H),
7.07, (t, J = 7.7 Hz, 1H), 7.21 (t, J = 8.0 Hz, 2H), 7.25 (d,
3.5.12 2-Phenyl-2-(phenylamino)butyronitrile
(Table 2, entry 6 [18, 27])
J = 9.8 Hz, 1H), 7.33–7.40 (m, 2H). 13C NMR (100.6 MHz,
4
49.9 (d, JCF = 2.0 Hz), 114.3, 114.6
CDCl3):
d
(d, 2JCF = 22.3 Hz), 116.7(d, 2JCF = 22.3 Hz),117.9,120.7,
1H NMR (400 MHz, CDCl3): d 1.07 (t, J = 7.4 Hz, 3H),
2.05-2.25 (m, 2H), 4.35 (s, 1H), 6.55 (m, 2H), 6.79
(t, J = 7.4 Hz, 1H), 7.09–7.13 (m, 2H), 7.34–7.45 (m, 3H),
7.61 (d, J = 8.24 Hz, 2H); 13C NMR (100.6 MHz,
CDCl3): d 8.9, 38.4, 62.4, 115.8, 119.8, 120.0, 125.7,
128.7, 129.0, 129.2, 138.4, 143.7.
4
3
122.9 (d, JCF = 3.1 Hz), 129.7, 133.1 (d, JCF = 8.2 Hz),
136.4 (d, 3JCF = 7.4 Hz), 144.4, 163.2 (d, 1JCF = 248.5 Hz).
19F NMR (376.4 MHz, CDCl3): d -111.3 (m, 1F).
3.5.7 2-Methyl-2-(phenylamino)propionitrile
(Table 2, entry 1 [20, 27, 37])
3.5.13 2-Methyl-3-phenyl-2-(phenylamino)propionitrile
(Table 2, entry 7 [45])
1H NMR (400 MHz, CDCl3): d 1.67 (s, 6H), 3.69 (brs, 1H,
NH), 6.88–6.92 (m, 3H), 7.22–7.26 (m, 2H). 13C NMR d
28.2, 49.0, 117.5, 120.8, 122.1, 129.3, 143.4.
1H NMR (400 MHz, CDCl3): d 1.57 (s, 3H). 3.08
(d, J = 13.6 Hz, 1H), 3.23 (d, J = 13.6 Hz, 1H), 3.62 (brs,
1H, NH), 6.85–6.89 (m, 3H), 7.18–7.21 (m, 2H), 7.22–7.24
(m, 2H), 7.27–7.32 (m, 3H). 13C NMR (100.6 MHz,
CDCl3): d: 26.0, 45.4, 53.1, 117.9, 121.0, 121.3, 127.9,
128.7, 129.4, 130.7, 133.7, 143.6.
3.5.8 2-Methyl-2-(phenylamino)butyronitrile (Table 2,
entry 2 [20, 27])
1H NMR d 1.10 (t, J = 7.1 Hz, 3H), 1.59 (s, 3H),
1.82–2.02 (m, 2H), 3.59 (brs, 1H, NH), 6.85–6.88 (m, 3H),
7.19–7.23 (m, 2H). 13C NMR (100.6 MHz, CDCl3): d 8.62,
25.3, 33.7, 53.6, 117.5, 120.8, 121.5, 129.4, 143.8.
3.5.14 2-Phenylamino-2-(1,2,3,4-tetrahydronaphthalene)
carbonitrile (Table 2, entry 8 [21])
3.5.9 3-Fluoro-2-methyl-2-(phenylamino)propionitrile
(Table 2, entry 3 [18, 37])
1H NMR (400 MHz, CDCl3): d 2.26–2.29 (m, 2H), 2.78–2.93
(m, 2H), 3.04 (d, J = 16.4 Hz, 1H), 3.42 (d, J = 16.4 Hz,
1H), 3.68 (brs, 1H, NH), 6.80–6.85 (m, 3H), 6.96–7.03 (m,
2H), 7.05–7.10(m, 2H), 7.14–7.18 (m, 2H). 13C NMR
(100.6 MHz, CDCl3): d 25.2, 31.8, 40.9, 52.0, 117.3, 120.8,
121.2, 126.6, 127.2, 129.0, 129.4, 130.5, 134.1, 143.6.
1H NMR (400 MHz, CDCl3): d 1.67 (m, 3H), 3.86 (brs,
1H, NH), 4.55 (dd, JHF = 46.6 Hz, JHH = 7.2 Hz, 2H),
6.94–7.02 (m, 3H), 7.23–7.31 (m, 2H). 13C NMR
3
(100.6 MHz, CDCl3): d 22.3 (d, JCF = 3.81 Hz), 53.6
123

Nafion–Fe catalyzed Strecker reaction
311
3.5.15 2-Methyl-2-(2-methylphenylamino)butyronitrile
(Table 3, entry 2)
3.5.21 2-(Morpholin-4-yl)-2-phenylacetonitrile (Table 4,
entry 7 [47])
1H NMR (400 MHz, CDCl3): d 1.16 (t, J = 7.5 Hz, 3H),
1.69 (s, 3H), 1.93–2.13 (m, 2H), 2,18 (s, 3H), 3.54 (brs, 1H,
NH), 6.84 (t, J = 7.3 Hz, 1H), 7.14 (d, J = 8.2 Hz, 2H),
7.18–7.22 (m, 1H). 13C NMR (100.6 MHz, CDCl3): d 8.5,
17.8, 25.3, 33.7, 52.9, 114.6, 119.8, 121.6, 124.8, 127.0,
130.8, 141.8. HRMS (ESI): m/z found for MH? 189.13868,
calculated for C12H17N2 189.13862.
1H NMR d 2.57–2.60 (m, 4H), 3.69–3.76 (m, 4H), 4.82 (s,
1H), 7.38–7.44 (m, 3H), 7.52–7.55 (m, 2H). 13C NMR d
50.1, 62.6, 66.8, 115.3, 128.1, 129.0, 129.3, 132.6.
3.5.22 2-(Morpholin-4-yl)-2-phenylbutyronitrile (Table 4,
entry 10)
1H NMR d 1.00 (t, J = 7.4 Hz, 3H), 1.43 (s, 3H), 1.82 (q,
J = 7.4 Hz, 2H), 2.61 (m, 4H), 3.74 (m, 4H). 13C NMR d
8.8, 39.3, 49.7, 66.6, 76.3, 120.9, 125.2, 128.6, 128.7,
141.0.
3.5.16 2-Methyl-2-(4-nitrophenylamino)butyronitrile
(Table 3, entry 3)
1H NMR d 1.17 (t, J = 7.5 Hz, 3H), 1.72 (s, 3H),
1.93–2.14 (m, 2H), 4.55 (brs, 1H, NH), 6.85 (d,
J = 9.2 Hz, 2H), 8.14 (d, J = 9.2 Hz, 2H). 13C NMR d
8.6, 25.0, 33.4, 52.6, 105.2, 113.9, 120.0, 126.1, 139.9,
149.6. HRMS (ESI): m/z found for MH? 220.10799, cal-
culated for C11H14N3O2 220.10805.
3.5.23 1-(Morpholin-4-yl)cyclohexanecarbonitrile
(Table 4, entry 11 [45, 47])
1H NMR d 1.23–1.31 (m, 1H), 1.47–1.55 (m, 4H),
1.59–1.65 (m, 1H), 1.72–1.79 (m, 2H), 2.07–2.11 (m, 2H),
2.62–2.64 (m, 4H), 3.70–3.76 (m, 4H). 13C NMR d 22.2,
25.0, 33.6, 47.1, 61.2, 67.1, 119.1.
3.5.17 2-(4-Methoxyphenylamino)-2-methylbutyronitrile
(Table 3, entry 4)
1H NMR d 1.13 (t, J = 7.5 Hz, 3H), 1.52 (s, 3H), 1.77-2.02
(m, 2H), 3.35 (brs, 1H, NH), 3.77 (s, 3H), 6.83 (d,
J = 9.0 Hz, 2H), 6.97 (d, J = 9.0 Hz, 2H). 13C NMR d
8.6, 25.0, 33.6, 55.5, 55.6, 114.5, 122.1, 123.1, 136.7,
155.7. HRMS (ESI): m/z found for MH? 205.1333, cal-
culated for C12H16N2O 205.13354.
3.5.24 1-(Pyrrolidin-1-yl) cyclohexanecarbonitrile
(Table 4, entry 12 [47–49])
1H NMR d 1.19–1.26 (m, 1H), 1.47–1.62 (m, 5H),
1.68–1.74 (m, 2H), 1.77–1.81 (m, 4H), 2.02–2.05 (m, 2H),
2.67–2.70 (m, 4H). 13C NMR d 22.4, 23.4, 25.0, 35.9, 48.0,
62.3, 119.8.
3.5.18 2-(4-Chlorophenylamino)-2-methylbutyronitrile
(Table 3, entry 5)
1H NMR d 1.13 (t, J = 7.5 Hz, 3H), 1.61 (s, 3H),
1.84–2.04 (m, 2H), 3.67 (brs, 1H, NH), 6.84 (d,
J = 8.9 Hz, 2H), 7.20 (d, J = 8.9 Hz, 2H). 13C NMR d
8.6, 25.1, 33.5, 53.6, 118.6, 121.3, 125.7, 129.4, 142.5.
4 Conclusion
In conclusion, we have developed a convenient protocol for
Strecker reaction of various ketones with anilines and
amines using the environmentally benign, recyclable Lewis
acid catalyst Nafion–Fe. We were able to significantly
reduce reaction times and obtained products of high purity
under solvent-free and microwave conditions. Our method
also provides an efficient alternate route for the existing
high pressure and stepwise methodologies for the Strecker
reaction of ketones and secondary amines. Simple reaction
set-up, easy work-up procedure, mild reaction conditions,
shorter reaction times, high purity of the products are the
notable features of the described methodology. Nafion–Fe
being a reusable, environmentally benign, highly effective
and easily accessible catalyst can make a significant con-
tribution in green chemistry field and satisfy the growing
demand for environmentally benign and clean synthetic
processes.
3.5.19 2-Methyl-2-(piperidin-1-yl)butyronitrile (Table 3,
entry 6 [46])
1H NMR d 1.00 (t, J = 7.4 Hz, 3H), 1.43 (s, 3H), 1.82 (q,
J = 7.4 Hz, 2H), 2.6–2.63 (m, 4H), 3.73–3.75 (m, 4H). 13
NMR d 7.7, 21.6, 30.2, 47.7, 60.3, 67.1, 120.0.
C
3.5.20 2-Methyl-2-(pyrrolidin-1-yl)butyronitrile (Table 3,
entry 7 [47])
1H NMR d 1.00 (t, J = 7.5 Hz, 3H), 1.48 (s, 3H),
1.66–1.76 (m, 1H), 1.80–1.88 (m, 4H), 1.85–1.91 (m, 1H),
2.69–2.72 (m, 4H). 13C NMR d 8.3, 23.5, 23.6, 32.4, 48.8,
61.3, 120.4.
123

312
G. K. Surya Prakash et al.
Acknowledgments Financial support from the Loker Hydrocarbon
Research Institute is gratefully acknowledged.
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