KF/clinoptilolite nanoparticles as an efficient nanocatalyst for the Strecker synthesis of α-aminonitriles

Article abstract of DOI:10.1007/s00706-020-02574-w

Abstract: Potassium fluoride impregnated on clinoptilolite nanoparticles (KF/CP NPs) have been explored to serve as an effective and inexpensive heterogeneous catalyst for the one-pot three-component Strecker synthesis of a variety of α-aminonitriles at room temperature in ethanol as a green solvent. KF/CP NPs have been synthesized using simple impregnation techniques in aqueous media from readily available inexpensive starting materials and displayed its initial catalytic activity even after five runs. The easy preparation and separation of catalyst, simple procedure, mild reaction conditions, and excellent yields of products render this method as an attractive sustainable option. Graphic abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s00706-020-02574-w

Monatshefte für Chemie - Chemical Monthly
https://doi.org/10.1007/s00706-020-02574-w
ORIGINAL PAPER
KF/clinoptilolite nanoparticles as an efcient nanocatalyst
for the Strecker synthesis of α‑aminonitriles
Razieh Oladee1 · Daryoush Zareyee1 · Mohammad A. Khalilzadeh1
Received: 8 July 2019 / Accepted: 12 March 2020
© Springer-Verlag GmbH Austria, part of Springer Nature 2020
Abstract
Potassium fuoride impregnated on clinoptilolite nanoparticles (KF/CP NPs) have been explored to serve as an efective
and inexpensive heterogeneous catalyst for the one-pot three-component Strecker synthesis of a variety of α-aminonitriles
at room temperature in ethanol as a green solvent. KF/CP NPs have been synthesized using simple impregnation techniques
in aqueous media from readily available inexpensive starting materials and displayed its initial catalytic activity even after
fve runs. The easy preparation and separation of catalyst, simple procedure, mild reaction conditions, and excellent yields
of products render this method as an attractive sustainable option.
Graphic abstract
R'
NC
O
H
NH2
TMSCN
N
H
R'
+
R
H
R
KF/CP NPs (20 mol%), EtOH, rt
Keywords Clinoptilolite · KF/CP · Aldehydes · Strecker · α-Aminonitriles · Three-component
Introduction
economical point of view. Accordingly, enormous eforts
have been devoted to the development of efcient, recy-
clable, and environmentally benign catalytic methods to
afect the Strecker reaction using nonpolluting reagents and
solvents. In this sense, we have recently reported Strecker
reaction by some heterogeneous catalysts [44, 45]. During
our ongoing eforts to search for environmentally friendly
and reusable nanocatalysts [44–50], we have found that KF/
clinoptilolite is a heterogeneous inexpensive solid cata-
lyst for some organic transformations [51–60]. Moreover,
impregnation of potassium fuoride on clinoptilolite (CP) as
a natural zeolite with a high internal surface area and high
cation exchange capability particularly for K+ is very sim-
ple without the need for any pre-activation [61, 62]. Armed
with these experiences, in the current study, with the aim of
developing a more convenient and simple approach towards
the construction of α-aminonitriles, we wish to report the
use of heterogeneous KF/CP NPs as recyclable catalyst in
the Strecker reaction (Scheme 1).
Strecker reaction [1] is one of the most straightforward and
preferred synthetic reactions in organic chemistry to aford
α-aminonitriles from the three-component coupling of an
amine, a carbonyl compound, and a cyanide source. Because
of the importance of α-aminonitriles as valuable interme-
diates for preparing S- and N-containing heterocycles [2],
versatile precursors of α-amino acids [3], and biologically
active molecules [4–7], employing new catalytic approaches
is currently a highly desirable goal and this reaction has
been considerably extended by the employment of various
catalysts, sources of amino and cyano groups, and use of
diferent solvents. Among various cyanide ion sources, tri-
methylsilyl cyanide (TMSCN) is a safer and easily handled
reagent [8–43]. Besides, performing the Strecker reaction
under green conditions using a heterogeneous catalyst will
not only improve the reaction from an ecological but also
* Daryoush Zareyee
zareyee@gmail.com
1
Department of Chemistry, Qaemshahr Branch, Islamic Azad
University, Qaemshahr, Iran
Vol.:(0123456789)
1 3

R. Oladee et al.
Scheme 1
R'
NC
O
H
NH2
TMSCN
N
R'
H
+
R
H
R
KF/CP NPs (20 mol%), EtOH, rt
change the yield of the reaction (Table 1, entry 7). A con-
trol experiment was performed in the absence of a catalyst
at room temperature and the desired product obtained in
trace amounts after 360 min (Table 1, entry 8). Interestingly,
the same reaction with CP and KF (Table 1, entries 9, 10)
yielded trace amounts and 35% of products, respectively.
Additionally, 42% of the related product obtained with using
bulk KF/CP after 240 min (Table 1, entry 11). These results
verify the catalytic efciency of KF/CP NPs. Thus, the best
results were obtained by the application of 20 mol% of KF/
CP NPs in EtOH at ambient temperature.
Table 1 Optimization conditions for reaction of benzaldehyde
(1 mmol), aniline (1 mmol), and TMSCN (2 mmol) in the presence
of diferent amounts of KF/CP NPs in diferent solvents at room tem-
perature
Entry
Catalyst/%mol
Solvent
Time /min
Yield/%a
1
2
3
4
5
6
7
8
20
20
20
20
20
10
30
–
CH2Cl2
Toluene
(Et)2O
H2O
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
90
90
240
240
35
120
50
360
360
360
240
30
50
45
Trace
92
75
91
Trace
Trace
35
At the next stage, the activity of the catalyst was tested
for the synthesis of various α-aminonitriles under optimized
reaction conditions to examine the universality of this cata-
lyst’s application (Table 2). The general efciency of this
reaction is evident from the variety of aryl aldehydes con-
taining both electron-withdrawing and electron-donating
groups which react in excellent yields within a short reac-
tion time (Table 2, entries 1–15). Also, the aniline-bearing
Br group in para-position (p-bromoaniline) concluded to
the related products with excellent yields in short reaction
times (Table 2, entries 16, 17). Noteworthy, trace amounts of
product were obtained when methyl amine and ethyl amine
were used as aliphatic amines (Table 2, entries 18, 19). How-
ever, the reaction proceeded efciently at room temperature
without the formation of any by-products. These conditions
are extremely convenient from a practical and economic
point of view since they use inexpensive recyclable KF/CP
NPs and avoid wasting reagents and allow a simple work-up
procedure. Summing up, a rapid, clean, and efcient method
for the synthesis of α-aminonitriles at room temperature is
reported and quantitative transformations achieved in short
reaction time.
9
10
11
CP (20)
KF (20)
20b
42
aIsolated yields
bBulk KF/CP was used instead of KF/CP NPs
Results and discussion
Prompted by our latest results regarding diferent heteroge-
neous catalyzed Strecker reactions [44, 45], we decided to
use KF/CP NPs for the promotion of the Strecker reaction.
The main reason for selection of KF/CP NPs as catalyst is
because of abundance, very low cost, and safety of naturally
occurring zeolite CP. The analysis of structure and size dis-
tribution of the nanoparticles (NPs) was performed by scan-
ning electron microscopy (SEM) and X-ray difraction, with
results matching the literature data. The size of prepared KF/
CP NPs was reported to be 41 nm [52–55].
For initial screening, the study was designed for the
synthesis of α-aminonitriles via Strecker reaction of ben-
zaldehyde (1.0 mmol), aniline (1.0 mmol), and TMSCN
(2.0 mmol) to investigate the suitability of KF/CP NPs
(20 mol%) as a catalyst in diferent reaction conditions
(Table 1). Our preliminary investigation showed that a yield
of 92% of the desired product was obtained when EtOH
was used as solvent at room temperature (Table 1, entry
5). Noteworthy, decreasing the amounts of KF/CP NPs
(10 mol%) gave the corresponding α-aminonitrile in 80%
yield even after prolonged reaction times (Table 1, entry 6),
and increasing the KF/CP NPs (30 mol%) did not notably
The proposed mechanism is described in Scheme 2. It
is plausible that the reaction begins with the formation of
bond between oxygen atom of carbonyl compounds and
surface of catalyst to produce iminium ion intermediates.
Then, the fuoride ion facilitates the formation of cyanide
ion and nucleophilic attack of cyanide ion to the iminium
ion intermediate leads to the formation of the corresponding
α-aminonitriles.
The possibility of the catalyst recyclability and reusabil-
ity was then investigated in this system through a series of
sequential synthesis of α-aminonitriles from benzaldehyde,
aniline and TMSCN as model substrates (Fig. 1). After
1 3

KF/clinoptilolite nanoparticles as an efcient nanocatalyst for the Strecker synthesis…
Table 2 Synthesis of α-aminonitriles from aldehydes, amine, and
Table 2 (continued)
TMSCN using KF/CP NPs in EtOH at room temperature
Reaction conditions: aldehyde (1.0 mmol), amine (1.0 mmol), and
TMSCN (2.0 mmol) with KF/CP NPs (20 mol%) in 5.0 cm3 EtOH at
room temperature
Entry Aldehyde Amine
Product
Time /min Yielda /%
O
NC
aIsolated yields
H
NH2
H
1
35
30
92
91
N
H
O
NC
H
completion of each run of reaction, hexane was added and
the reaction mixture was fltered and washed with hexane.
Then, the recovered catalyst was used in the successive runs.
The results showed that the catalyst could be efectively used
for at least fve cycles. The decrease in the yield after the
ffth use of the catalyst may be attributed to the leaching of
KF from CP. After performing the ffth cycle of the reaction,
the solid material was fltered out and then the presence of
fuoride ions in the fltrate validated by SPADNS spectro-
photometric method proved the leaching of KF during the
recycling of catalyst.
NH2
H
N
2
H
Me
Me
NH2
O
NC
H
H
N
H
3
40
90
OMe
OMe
O
NH2
NH2
NC
H
H
N
4
5
6
25
40
92
81
H
MeO
MeO
O
NC
H
H
N
H
OH
OH
O
NH2
NC
H
H
N
H
40
45
91
92
HO
HO
Conclusion
O
NH2
NH2
NC
H
H
H
N
7
8
H
Cl
Cl
In summary, this study has shown that environmentally
friendly heterogeneous KF/CP NPs catalyst can be used to
promote highly efcient one-pot, three-component Strecker
reaction of a range of aldehydes and aniline derivatives
with TMSCN in EtOH at room temperature to produce
α-aminonitriles. However, the reaction is limited to aromatic
amines. In this process, the catalyst can be easily recov-
ered and can be reused for the next reactions without any
treatment for fve consecutive runs. This method has advan-
tages such as mild conditions, high yields, short reaction
times, easy work-up, and cost efective for the synthesis of
α-aminonitriles. As a result of high efciency and activity as
well as recyclability and low cost of catalyst, further applica-
tions of this catalyst to other synthetically useful transforma-
tions are currently being investigated.
O
NC
H
N
H
30
40
94
89
Cl
Cl
O
NH2
NH2
NH2
NC
H
H
H
N
9
H
Cl
Br
Cl
O
NC
H
N
10
40
84
H
Br
O
NC
H
H
N
H
11
12
45
55
92
89
NO2
NO2
O
NH2
NH2
NC
H
H
N
H
O2
N
O2
N
O
NC
H
H
N
H
13
14
15
16
17
55
40
45
25
20
80
89
90
91
88
NC
NC
NH2
NH2
Experimental
O
O
O
NC
NC
H
O
O
H
N
H
The raw material was an Iranian commercial CP (Afrand-
tooska Company) from deposits in the region of Semnan. All
chemicals used in this work were purchased from Fluka or
Sigma-Aldrich and were employed without further purifca-
tion. The morphology of nanoparticles of KF/clinoptilolite
was characterized by scanning electron microscopy (SEM)
using a Holland Philips XL30 microscope. Crystalline struc-
ture of KF/CP (NPs) was characterized by X-ray difraction
(XRD) analysis at room temperature using a Holland Philips
Xpert X-ray powder difractometer, with CuKα radiation
(λ = 0.15406 nm). The average crystallite size was calcu-
lated using Scherrer’s formula: D=0.9λ/β cosθ. Thin-layer
chromatography (TLC) was performed using 60 mesh silica
H
S
S
H
N
H
NH2
NH2
Br
NC
H
H
N
Br
H
Br
O
NC
H
H
N
Br
H
H3
C
Me
O
O
NC
NC
H
CH3NH2
CH3
H
H
N
18
19
40
40
Trace
Trace
H
H
C2H5NH2
C2H5
N
H
1 3

R. Oladee et al.
Scheme 2
carried out in a 10 cm3 round bottom fask using 0.12 g KF/
CP NPs (20 mol%) in 5.0 cm3 ethanol at room tempera-
ture. After completion of the reaction monitored by thin-
layer chromatography, the reaction mixture was fltered and
washed with hexane to recover the catalyst. Aqueous sodium
bicarbonate (5.0 cm3 of a 5.0% solution) was then added and
the mixture extracted with hexane (3×5.0 cm3). The com-
bined organic phases were dried over anhydrous magnesium
sulfate. Then, the reaction solution was concentrated under
vacuum and materials were subjected to column chromatog-
raphy on fash silica.
93
92
92
91
100
80
60
40
20
0
88
80
1
2
3
4
5
6
Acknowledgements The authors acknowledge the Islamic Azad Uni-
versity of Qaemshahr Research Councils for support of this work.
Fig. 1 Reusability of KF/CP NPS (20 mol%) for the Strecker reaction
of benzaldehyde (1 mmol), aniline (1 mmol), and TMSCN (2 mmol)
after 35 min at room temperature
gel Merck TLC plates. All values were analyzed using an
HP GC 6890 that was equipped with a DB-5 CP column
(30 m×0.32 mm×0.5 m).
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1 3