Boric acid catalysed synthesis of α-Aminonitriles by a three-component reaction at room temperature

Article abstract of DOI:10.3184/174751912X13352842814921

A simple, efficient, and cost-effective method has been developed for the one-pot, three-component condensation reaction of trimethylsilyl cyanide, aldehydes and aromatic amines using boric acid as a heterogeneous solid acid catalyst, under solvent-free conditions. α-Aminonitriles were synthesised relatively quickly in good yields at room temperature.

Full text of DOI:10.3184/174751912X13352842814921

326 RESEARCH PAPER
JUNE, 326–327
JOURNAL OF CHEMICAL RESEARCH 2012
Boric acid catalysed synthesis of α-aminonitriles by a three-component
reaction at room temperature
Zahed Karimi-Jaberi,* and Abdolaziz Bahrani
Department of Chemistry, Firoozabad Branch, Islamic Azad University, PO Box 74715-117 Firoozabad, Fars, Iran
A simple, efficient, and cost-effective method has been developed for the one-pot, three-component condensation
reaction of trimethylsilyl cyanide, aldehydes and aromatic amines using boric acid as a heterogeneous solid acid
catalyst, under solvent-free conditions. α-Aminonitriles were synthesised relatively quickly in good yields at room
temperature.
Keywords: α-aminonitriles, boric acid, trimethylsilyl cyanide, solvent-free conditions
α-Aminonitriles are not only versatile intermediates for the
synthesis of α-amino acids,1 and various nitrogen containing
heterocycles,2,3 such as imidazoles and thiadiazoles but also
show a valuable dual reactivity, which has a wide range of
synthetic applications.4 In addition, the α-aminonitrile moiety
has been found to occur in saframycin A, a natural product
with anti-tumour activity, and in phtalascidin, a synthetic
analogue, which exhibits even greater potency.5 The Strecker
reaction,6 provides one of the most important methods for
the synthesis of α-aminonitriles. Numerous modifications
have been made to the original Strecker reaction, using a vari-
ety of cyanating agents such as hydrogen cyanide, sodium
or potassium cyanide, Bu3SnCN, bis(dialkylamino)cyanobora
nes, diethylphosphorocyanidate, and trimethylsilyl cyanide
(TMSCN).7–11 TMSCN is a safer, more effective, and more
easily handled anion source compared to others. The efficiency
of the reaction has been increased by the use of various
catalysts.7–19
However, these methodologies show varying degrees of
success as well as limitations due to the use of toxic organic
solvents, expensive catalysts, prolonged reaction times,
and the requirement for special apparatus, or harsh reaction
conditions. Thus, there is a need for an alternative route for
the production of α-aminonitriles, which overcomes these
limitations.
Following our systematic studies directed towards the
development of practical, safe, and environmentally-friendly
procedures for one-pot multi-component reactions,20–23 we
have developed the first procedure for a boric acid promoted
reaction of aldehydes, amines, and TMSCN leading to the
synthesis of α-aminonitriles under solvent-free conditions at
room temperature (Scheme 1).
To optimise the reaction conditions, treatment of benzalde-
hyde and aniline with TMSCN was used as a model reaction.
Reactions under different conditions and with various molar
ratios of substrates in the presence of boric acid revealed
that boric acid gave the corresponding α-aminonitrile in
88% yield in 10 min under solvent-free conditions at room
temperature.
To show the generality of the present method the optimised
system was utilised for the synthesis of other α-aminonitrile
derivatives. Various examples illustrating this novel and
general method for the synthesis of α-aminonitriles are
summarised in Table 1.
Various functionalities present in the aryl aldehydes, such as
chloro, fluoro and methyl groups as well as arylamines such as
chloro, bromo and methylaniline were tolerated under these
conditions at room temperature (Table 1).
The catalytic system also worked well with aliphatic alde-
hydes to generate the corresponding products with good yields
(entries 11 and 12, Table 1). Even with an α,β-unsaturated
aldehyde, a good yield of the desired product (80%) was
obtained without the formation of other side products (Table 1,
entry 12).
To illustrate the need of boric acid for these reactions an
experiment was conducted in the absence of boric acid. The
yield in this case was about 10% after 1 hour. Obviously, the
boric acid is an important component of the reaction.
1
All products were identified by H NMR, 13C NMR and
IR spectroscopic methods and the results were confirmed
by comparison with those available in the literature. Table 2
compares the features of the previously reported procedures
with those of the present methodology for the reaction of
benzaldehyde, aniline and trimethylsilyl cyanide.
Boric acid (H3BO3) is a useful and environmentally-benign
catalyst which can effectively promote organic reactions
such as the aza-Michael addition,24 the Mannich reaction,25 and
the synthesis of alkylidene bisamides.26 It has been utilised
by our group for the synthesis of dibenzoxanthenes,20 α-
aminophosphonates,21 and dihydroquinazolinones.22 It offers
milder conditions relative to common mineral acids. Boric
acid is a readily available and inexpensive reagent and can
conveniently be handled and removed from the reaction
mixture. Hence, the remarkable catalytic activities together
with its operational simplicity make it the most suitable cata-
lyst for the synthesis of α-aminonitriles.
In conclusion this paper describes a convenient and efficient
process for the synthesis of α-aminonitriles by a one-pot reac-
tion of trimethylsilyl cyanide, aldehydes and aromatic amines
in the presence of boric acid at room temperature under
solvent-free conditions. This method offers some advantages
in terms of simplicity of performance, short reaction times,
solvent-free condition, low cost, and it follows along the
line of green chemistry. The catalyst is readily available and
inexpensive and can conveniently be handled and removed
from the reaction mixture.
Experimental
Chemicals were purchased from Merck, Fluka and Aldrich Chemical
Companies. IR spectra were run on a Shimadzu IR spectroscopy. The
1H and 13C NMR was run on Bruker Avance 300 (300 MHz). Melting
points were recorded on an Electrothermal type 9100 melting point
apparatus in open capillary tubes and are uncorrected.
Synthesis of α-aminonitriles 3a–l; general procedure
Scheme 1
A mixture of the aldehyde (2 mmol), boric acid (0.2 g), amine
(2.4 mmol) and trimethylsilyl cyanide (2.4 mmol) was stirred at room
temperature for the appropriate time indicated in Table 1.
* Correspondent. E-mail: z.karimi@iauf.ac.ir

JOURNAL OF CHEMICAL RESEARCH 2012 327
Table 1 Synthesis of α-aminonitriles using boric acid as catalyst
Entry
R
R′
Product
Time/min
Yield/%
M.p. /°C
Lit. M.p./°C
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
Ph
3a
3b
3c
3d
3e
3f
3g
3h
3i
10
15
10
20
10
15
15
15
25
15
30
30
88
85
85
70
82
75
85
90
82
75
77
80
80–82
98–100
110–112
117–119
76–77
90–93
92–94
70–72
84–86
96–98
Oil
80–827
98–1009
109–11212
115–1177
76–7812
91–937
4-FC6H4
4-ClC6H4
2,4-Cl2C6H3
4-CH3C6H4
Ph
Ph
Ph
4-ClC6H4
4-FC6H4
CH3(CH2)8
trans-PhCH=CH
Ph
4-BrC6H4
3,4-(CH3)2C6H3
2-CH3C6H4
4-CH3C6H4
2-ClC6H4
Ph
92–947
72–7312
84–8511
95–9712
Oil12
10
11
12
3j
3k
3l
Ph
117–119
117–11918
Table 2 Comparison of efficiency of various catalysts in the
synthesis of α-aminonitrilesa
J = 8.0 Hz, 2H). 13C NMR (CDCl3): δ 143.4, 134.7, 131.3, 130.0,
129.8, 127.9, 127.7, 124.1, 120.4, 118.9, 112.2, 50.7, 17.8; IR (KBr):
υ 3365, 2935, 2857, 2237, 1605, 1517, 1461, 1275, 1035, 791 cm−1.
2-(N-2-Chloroanilino)-2-(4-fluorophenyl)acetonitrile (3j): White
Conditions
Time/h Yield/%
Ref.
8
1
crystalline solid; H NMR (CDCl3): δ 4.66 (d, J = 8.1 Hz, 1H), 5.45
Silica-based scandium (III)
interphase
14
94
(d, J = 8.1 Hz, 1H), 6.91–6.95 (m, 2H), 7.15–7.35 (m, 4H), 7.59–7.69
(m, 2H); 13C NMR (75.4 MHz, CDCl3): δ 144.3, 136.0, 135.5, 132.4,
130.0, 129.8, 128.5, 127.7, 120.5, 117.8, 114.2, 49.5; IR (KBr):
υ 3410, 2931, 2230, 1610, 1520, 1461, 1269, 1051, 790 cm−1.
Montmorillonite KSF, CH2Cl2
BiCl3, CH3CN
Silica sulfuric acid, CH2Cl2
NiCl2, CH3CN
RhCl3.3H2O, CH3CN
[bmim][ClO4]
H3BO3
3.5
10
6
12
1
0.5
10 min
90
84
88
92
86
86
88
12
13
14
15
16
Received 20 February 2012; accepted 20 March 2012
Paper 1201175 doi: 10.3184/174751912X13352842814921
Published online: 4 June 2012
17
This work
a Times and yields refer to the reaction of benzaldehyde, aniline
and TMSCN.
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