Praseodymium trifluoromethylsulfonate as an efficient and recyclable catalyst for the synthesis of α-aminonitriles

Article abstract of DOI:10.1081/SCC-200051702

Praseodymium trifluoromethylsulfonate (triflate) has been found to be an efficient and recyclable catalyst for the synthesis of α-aminonitrile by a one-pot, three-component condensation of aldehydes, amines, and trimethylsilyl cyanide at room temperature.

Full text of DOI:10.1081/SCC-200051702

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Praseodymium Trifluoromethylsulfonate as
an Efficient and Recyclable Catalyst for the
Synthesis of α‐Aminonitriles
Surya K. De a & Richard A. Gibbs a
a Department of Medicinal Chemistry and Molecular Pharmacology, School
of Pharmacy, Purdue Cancer Center , Purdue University , West Lafayette,
Indiana, USA
Published online: 21 Aug 2006.
To cite this article: Surya K. De & Richard A. Gibbs (2005) Praseodymium Trifluoromethylsulfonate as
an Efficient and Recyclable Catalyst for the Synthesis of α‐Aminonitriles, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 35:7, 961-966, DOI: 10.1081/
SCC-200051702
To link to this article: http://dx.doi.org/10.1081/SCC-200051702
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Synthetic Communicationsw, 35: 961–966, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200051702
Praseodymium Trifluoromethylsulfonate
as an Efficient and Recyclable Catalyst
for the Synthesis of a-Aminonitriles
Surya K. De and Richard A. Gibbs
Department of Medicinal Chemistry and Molecular Pharmacology,
School of Pharmacy, Purdue Cancer Center, Purdue University,
West Lafayette, Indiana, USA
Abstract: Praseodymium trifluoromethylsulfonate (triflate) has been found to be an
efficient and recyclable catalyst for the synthesis of a-aminonitrile by a one-pot,
three-component condensation of aldehydes, amines, and trimethylsilyl cyanide at
room temperature.
Keywords: Aldehydes, amines, praseodymium triflate, recyclability, trimethylsilyl
cyanide
In view of the tremendous versatility of a-aminonitriles in synthetic organic
chemistry as important intermediates for the synthesis of amino acids[1] and
nitrogen-containing heterocycles,[2] a plethora of procedures has been
reported for their preparation.[3–10] The classical Strecker reaction is
generally carried out with alkaline cyanides in aqueous solution. Among
various cyanide-ion sources, trimethylsilyl cyanide is a more reactive
reagent than hydrogen cyanide, sodium cyanide, or potassium cyanide.
However, many of these methods have some drawbacks such as low yields
of the products, long reaction times, harsh reaction conditions, difficulties in
Received in the USA December 10, 2004
Address correspondence to Surya K. De, Department of Medicinal Chemistry and
Molecular Pharmacology, School of Pharmacy, Purdue Cancer Center, Purdue
University, West Lafayette, IN 47907, USA. Fax: 765-494-1414; E-mail: skd125@
pharmacy.purdue.edu

962
S. K. De and R. A. Gibbs
workup, the requirement for an inert atmosphere, and the use of stoichio-
metric[10] and/or relatively expensive reagents.[8,9] Moreover, many of the
catalysts used for these reactions are deactivated or sometimes decomposed
by amines and water that are present during imine formation. Therefore,
there is need to search for a better catalyst in terms of operational simplicity,
reusability, and economic viability.
Most recently, lanthanide triflates have been introduced as promising
mild and selective reagents in organic synthesis.[11] The catalyst praseody-
mium triflate is commercially available, five times less expensive than
scandium triflate, and can be used for the preparation of a-aminonitriles
through a one-pot, three-component coupling of aldehydes, amines, and tri-
methylsilyl cyanide. Whereas most conventional Lewis acids are decomposed
in the presence of water, Pr(OTf)3 is stable in water and does not decompose
under aqueous workup conditions. Thus, recycling is often possible. The
reaction of benzaldehyde and aniline with TMSCN in the presence of a
catalytic amount of Pr(OTf)3 afforded the corresponding 2-(N-anilino)-2-
phenylacetonitrile in 89% yield. Thus, various aromatic, aliphatic, and hetero-
cyclic aldehydes were coupled with a wide range of amines and trimethylsilyl
cyanide in a one-pot operation in the presence of a catalytic amount of
Pr(OTf)3 to give the corresponding a-aminonitriles. No undesired side
product (such as cyanohydrin trimethyl silyl ether, an adduct between the
aldehyde and trimethylsilyl cyanide) was observed because the rapid
formation of the imine intermediate. The attempted aminocyanation of
ketones did not afford the desired products in satisfactory yield. However,
acid-sensitive aldehydes such as furfuraldehyde afforded the desired product
in high yield (Scheme 1). The results shown in Table 1 clearly indicate the
scope and generality of the reaction with respect to various aldehydes and
amines.
In comparison with other catalysts such as Sc(OTf)3,[8] InCl3,[9] and KSF-
clay,[10] which are recently reported in the aminocyanation of benzaldehyde,
Pr(OTf)3 employed here shows more catalytic reactivity than InCl3 and
KSF-clay in terms of the amount of catalyst and yields of the product
(Table 2).
In conclusion, a very simple, mild, and practical method has been
developed for the synthesis of a-aminonitriles through a one-pot, three
component coupling of aldehydes, amines, and trimethylsilyl cyanide using
Scheme 1.

Praseodymium Trifluoromethylsulfonate
963
Table 1. Pr(OTf)3 catalyzed synthesis of a-amino nitriles with trimethylsilyl cyanide
Time Yielda
Entry Aldehyde
Amine
(h)
(%)
1
2
3
4
5
6
7
Benzaldehyde
Aniline
Aniline
10
89/82b
81/76b
77
4-Chlorobenzaldehyde
Isobutyraldehyde
Decylaldehyde
3-Methoxybenzaldehyde
Furfural
11
12
10
8
Benzyl amine
Aniline
79
91
Benzyl amine
Benzyl amine
Benzyl amine
8
82
86
Thiophene
2-carboxaldehyde
Benzaldehyde
9
8
9
Morpholine
Pyrrolidine
10
8
78
81
74
88
77
79
81
Butyraldehyde
Benzaldehyde
Benzaldehyde
10
11
12
13
14
Furfurylamine
3-Methoxybenzyl amine
Butyl amine
10
10
10
9
Benzaldehyde
2,4-Dimethoxybenzaldehyde 3,4,5-Trimethoxyaniline
4-Methylbenzaldehyde Aniline
10
aAll products were characterized by comparison of their mp, IR, and 1H NMR
spectra with those of authentic samples (Refs.[9,10]).
bIsolated yield with reused catalyst.
a catalytic amount of praseodymium triflate. Further, the catalyst can be
readily recovered and reused, thus making the procedure more environmen-
tally acceptable.
EXPERIMENTAL
All products are known and were identified by comparing of their spectral data
and physical properties with those of authentic samples.[9,10] The progress of
Table 2. Comparison of the effect of catalysts in the synthesis of 2-(N-benzylamino)-
2-phenylacetonitrile
Catalyst load
(mol%)
Time
(h)
Yield
(%)
Catalyst
Sc(OTf)3
InCl3
10
20
5
88 (Ref.[8]
73 (Ref.[9]
)
)
30
more than 100
10
KSF-clay
Pr(OTf)3
4.5
10
87 (Ref.[10]
89
)

964
S. K. De and R. A. Gibbs
reaction was monitored by thin-layer chromatography on silica gel. All yields
refer to isolated products.
Typical Procedure
A mixture of benzaldehyde (212 mg, 2 mmol), benzyl amine (214 mg,
2 mmol), and trimethylsilyl cyanide (300 mg, 3 mmol) in dry acetonitrile
(2 mL) was stirred in the presence of anhydrous commercially available
(Aldrich) praseodymium triflate (118 mg, 10 mol%) at room temperature.
After completion of reaction (TLC), the reaction mixture was extracted with
ethyl acetate (2 ꢀ 20 mL). The organic layer was washed with water
(20 mL) and satd. brine (20 mL), dried (MgSO4), and concentrated in vacuo.
The residue was chromatographed over silica gel (30% ethyl acetate in
hexane) to afford the pure product. The aqueous layer containing the
catalyst can be evaporated under reduced pressure (20 mm Hg pressure,
1008C temperature) to give a white solid, which is reused for the next
reaction. The IR spectrum of the recovered catalyst was identical to that of
the commercially available catalyst (Aldrich). The catalyst can be recycled
and reused three times without any significant loss of activity.
Product characterization data: 2-(N-Anilino)-2-phenylacetonitrile
1
(entry 1) H NMR (300 MHz, CDCl3) d 4.02 (br s, 1 H), 5.40 (s, 1 H), 6.74
(d, J ¼ 7.8 Hz, 2 H), 6.89 (t, J ¼ 7.8 Hz, 1 H), 7.24 (t, J ¼ 7.8 Hz, 2 H),
7.41–7.49 (m, 3 H), 13C NMR (75 MHz, CDCl3) d 50.6, 114.8, 118.8,
120.6, 127.7, 129.7, 130.1, 130.2, 134.5, 145.6; EIMS m/z 208 (Mþ), 180,
116, 91, 77, 55; HRMS calcd. for C14H12N2 208.1004, found 208.1006.
1
2-(N-Anilino)-2-(4-chlorophenyl)acetonitrile (entry 2) H NMR
(300 MHz, CDCl3) d 4.01 (br s, 1 H), 5.39 (s, 1 H), 6.75 (d, J ¼ 8Hz, 2H), 6.91
(t, J ¼ 7.8Hz, 1H), 7.15 (t, J ¼ 7.9Hz, 2H), 7.38 (d, J ¼ 7.8 Hz, 2 H), 7.61
(d, J ¼ 8Hz, 2H); 13C NMR (75 MHz, CDCl3) d 49.7, 114.2, 117.7, 120.8,
128.5, 129.4, 129.6, 132.3, 135.5, 144.4; EIMS m/z 242 and 244 (Mþ), 149,
114, 91, 77, 59; HRMS calcd. for C14H11ClN2 242.0610, found 242.0608.
1
2-(N-Benzylamino)-2-isopropylacetonitrile (entry 3) H NMR (300 MHz,
CDCl3) d 1.08 (d, J ¼ 6.5 Hz, 3 H), 1.09 (d, J ¼ 6.5 Hz, 3 H), 1.56 (br s,
1 H), 1.97–2.02 (m, 1 H), 3.24 (d, J ¼ 6 Hz, 1 H), 3.80 (d, J ¼ 13 Hz, 1 H),
4.07 (d, J ¼ 13 Hz, 1 H), 7.24–7.43 (m, 5 H); 13C NMR (75 MHz,
CDCl3) d 18.2, 19.3, 31.3, 51.8, 56.3, 119.3, 127.5, 128.4, 128.7, 138.4;
EIMS m/z 188 (Mþ); HRMS calcd. for C12H16N2 188.1313, found 188.1316.
1
2-(N-Anilino)-2-decylacetonitrile (entry 4) H NMR (300MHz, CDCl3)
d 0.91 (t, J ¼ 6.7 Hz, 3 H), 1.18–1.38 (m 12 H), 1.50–1.64 (m. 2 H),
1.81–1.91 (m, 2 H), 3.81 (br s, NH), 4.02–4.15 (m, 1 H), 6.61 (d, J ¼ 8 Hz,
2 H), 6.81 (t, J ¼ 7.8 Hz, 1 H), 7.21 (t, J ¼ 7.8 Hz, 2 H); EIMS m/z 258
(Mþ), 185, 155, 121, 77, 55. HRMS calcd. for C17H26N2 258.2095, found
258.2092.

Praseodymium Trifluoromethylsulfonate
965
1
2-(N-Benzylamino)-2-(3-methoxyphenylacetonitrile (entry 5) H NMR
(300 MHz, CDCl3) d 1.84 (br s, 1 H), 3.76 (s, 3 H), 3.95 (AB, q, J ¼ 13 Hz,
2 H), 4.65 (s, 1 H), 6.85 (dd, J ¼ 2.4, 9 Hz, 1 H), 7.14–7.36 (m, 2 H),
7.28–7.43 (m, 6 H); 13C NMR (75 MHz, CDCl3) d 51.6, 53.9, 55.7, 113.4,
114.8, 119.2, 119.8, 128.5, 129.7, 128.8, 130.4, 136.7, 138.6, 160.4; EIMS
m/z 252 (Mþ), 122, 91, 77; HRMS calcd. for C16H16N2O 252.1262,
found 252.1258.
1
2-(N-Benzylamino)-2-furfurylacetonitrile (entry 6) H NMR (300MHz,
CDCl3) d 1.95 (br s, 1 H), 3.94 (AB, q, J ¼ 13 Hz, 2 H), 4.75 (s, 1 H),
6.27–6.32 (m, 1 H), 7.16–7.52 (m, 7 H); 13C NMR (75 MHz, CDCl3) d 47.9,
51.4, 109.2, 111.5, 127.5, 127.8, 128.5, 128.9, 138.2, 143.8, 147.9; EIMS
m/z 212 (Mþ); HRMS calcd. for C13H12N2O 212.0950, found 212.0955.
1
2-(N-Benzylamino)-2-thiophenylacetonitrile (entry 7) H NMR
(300 MHz, CDCl3) d 2.02 (br s, 1 H), 3.96 (AB, q, J ¼ 13Hz, 2 H), 4.91
(s, 1 H), 6.94–6.98 (m, 1 H), 7.21–7.45 (m, 7 H); 13C NMR (75 MHz, CDCl3)
d 49.7, 51.4, 118.4, 126.7, 127.3, 128.3, 128.7, 128.9, 129.2, 138.4, 138.9;
EIMS m/z 228 (Mþ); HRMS calcd. for C13H12N2S 228.0721, found 228.0725.
2-(N-Morpholino)-2-phenylacetontrile (entry 8) 1H NMR (300 MHz,
CDCl3) d 2.51–2.63 (m, 4 H), 4.68–4.79 (m, 5 H), 7.35–7.56 (m, 5 H); 13C
NMR (75 MHz, CDCl3) d 50.4, 62.1, 62.8, 115.7, 128.5, 129.4, 129.8,
133.1; EIMS m/z 202 (Mþ), HRMS calcd. for C12H14N2O 202.1106, found
202.1109.
2-n-Propyl-2-(N-pyrrolidino)acetonitrile
(entry
9) 1H
NMR
(300 MHz, CDCl3) 0.98 (t, J ¼ 7.7 Hz, 3 H), 1.42–1.51 (m, 2 H), 1.69–1.89
(m, 6 H), 2.62–2.71 (m, 4 H), 3.75 (t, J ¼ 7.5 Hz, 1 H); 13C NMR (75 MHz,
CDCl3) d 11.6, 17.4, 21.4, 32.9, 47.9, 53.2, 94.4; EIMS m/z 152 (Mþ),
HRMS calcd. for C9H16N2 152.1313, found 152.1311.
2-(N-furfurylamino)-2-phenylacetonitrile (entry 10) 1H NMR
(300 MHz, CDCl3) 1.82 (br s, 1 H), 4.01 (s, 2 H), 4.79 (s, 1 H), 6.21–6.41
(m, 2 H), 7.31–7.56 (m, 6 H); EIMS m/z 212 (Mþ), 186, 81, 77; HRMS
calcd. for C13H12N2O 212.0949, found 212.0951.
1
2-(N-3-Methoxybenzylamino)-2-phenylacetonitrile (entry 11) H NMR
(300 MHz, CDCl3) d 1.86 (br s, 1 H), 3.81 (s, 3 H), 3.94 (AB, q, J ¼ 13 Hz,
2H), 4.71 (s, 1H), 6.81–6.96 (m, 3H), 7.24 (t, J ¼ 7.8Hz, 1H), 7.30–7.58
(m, 5 H); 13C NMR (75 MHz, CDCl3) 51.4, 53.7, 55.6, 96.6, 113.4, 114.2,
119.1, 120.9, 127.6, 129.4, 130.1, 135.4, 140.1, 160.2; EIMS m/z 252 (Mþ),
122, 91, 77; HRMS calcd for C16H16N2O 252.1262, found 252.1265.
1
2-(N-n-Butylamino)-2-phenylacetonitrile (entry 12) H NMR (300 MHz,
CDCl3) d 0.92 (t, J ¼ 7.2 Hz, 3 H), 1.25–1.47 (m, 4 H), 2.68–2.78 (m, 2 H),
4.74 (s. 1 H), 7.38–7.38 (m, 3 H), 7.65–7.71 (m, 2 H); 13C NMR (75 MHz,
CDCl3) d 14.2, 20.6, 32.3, 47.5, 54.8, 119.4, 127.7, 129.3, 135.5; EIMS
m/z 188 (Mþ); HRMS calcd. for C12H16N2 188.2689, found 188.2693.
2-(N-3,4,5-Trimethoxyanilino)-2-(2,4-dimethoxyphenyl)acetonitrile
(entry 13) 1H NMR (300 MHz, CDCl3) d 3.76 (s, 3 H), 3.81 (s, 3 H), 3.82

966
S. K. De and R. A. Gibbs
(s, 6 H), 3.86 (s, 3 H), 4.18 (br s, 1 H), 5.44 (s, 1 H), 6.01 (s, 2 H), 6.46–6.53
(m, 2 H), 7.39 (d, J ¼ 9 Hz, 1 H); EIMS m/z 358 (Mþ); HRMS calcd. for
C19H22N2O5 358.1529, found 358.1531.
2-(N-Anilino)-2-(4-methylphenyl)acetonitrile (entry 14) 1H NMR
(300 MHz, CDCl3) d 2.41 (s, 3 H), 3.90 (s, 1 H), 5.41 (s, 1 H), 6.78
(d, J ¼ 8 Hz, 2 H), 6.91 (t, J ¼ 7.8 Hz, 1 H), 7.21–7.31 (m, 4 H), 7.50
(d, J ¼ 8 Hz, 2 H), 7.51 (d, J ¼ 8 Hz, 2 H); EIMS m/z 222 (Mþ), 176, 103,
77; HRMS calcd. for C15H14N2 222.1156, found 222.1158.
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