H2SO4/Silicagel: Highly efficient catalyst for the synthesis of α-aminonitriles using trimethysilyl cyanide

Article abstract of DOI:10.1007/s00706-007-0740-0

The multicomponent Strecker reaction using trimethylsilyl cyanide was performed at room temperature and α-aminonitriles were prepared in excellent yields in the presence of a catalytic amount of H₂SO ₄ adsorbed on silica gel.

Full text of DOI:10.1007/s00706-007-0740-0

Monatshefte fu¨r Chemie 139, 27–29 (2008)
DOI 10.1007/s00706-007-0740-0
Printed in The Netherlands
H2SO4=Silicagel: Highly Efficient Catalyst for the Synthesis
of a-Aminonitriles Using Trimethysilyl Cyanide
ꢀ
Hossien A. Oskooie, Majid M. Heravi , Akbar Sadnia, Fatemeh Jannati,
and Farahnaz K. Behbahani
Department of Chemistry, School of Sciences, Azzahra University, Vanak, Tehran, Iran
Received April 30, 2007; accepted June 12, 2007; published online November 21, 2007
# Springer-Verlag 2007
Summary. The multicomponent Strecker reaction using tri-
some of the Lewis acids used as well as their hydro-
methylsilyl cyanide was performed at room temperature and
ꢀ-aminonitriles were prepared in excellent yields in the pres-
ence of a catalytic amount of H2SO4 adsorbed on silica gel.
lysis products are toxic [20]. Therefore, there is a
further scope to explore milder, safer, and more ef-
ficient protocols for this reaction. One of the initial
drawbacks of this reaction is the use of highly tox-
ic cyanide derivatives. In order to avoid partially
this inconvenience, the use of trimethylsilyl cyanide
(TMSCN) has been introduced. The synthetic utility
of supported reagents has been demonstrated during
the past ten years [21].
In recent years it has been shown that sulfuric acid
adsorbed on silica gel can be used as a multipurpose
acid catalyst [22]. In continuation of our interest per-
forming reactions on solid supports [23], we now re-
port in this paper the synthesis of ꢀ-aminonitriles
using trimethylsilyl cyanide catalyzed by sulfuric acid
adsorbed on silica gel as an easily available, inexpen-
sive, and relatively green catalyst.
Keywords. Trimethylsilyl cyanide; ꢀ-Aminonitriles; H2SO4=
silica gel; Strecker reaction; Multi component reactions.
Introduction
The Strecker reaction, discovered in 1850 [1], has
been recognized as the first multicomponent reaction
[2] published ever and has a central importance to
the life sciences [3]. The three-component coupling
of an amine, a carbonyl compound (generally an
aldehyde), and either hydrogen cyanide or its alka-
line metal cyanides to give ꢀ-aminonitriles [4] con-
stitutes an important indirect route in the synthesis
of ꢀ-amino acids [5, 6].
More recent protocols involve the use of strong
Lewis acids, such as lithium perchlorate [7], polymeric
scandium triflamide [8], vanadyl triflate [9], nickel(II)
chloride [10], zinc halides [11], ruthenium(III) chlo-
ride [12], praseodymium triflate [13], ytterbium
triflate [14], bismuth(III) chloride [15], montmoril-
Results and Discussion
The reaction of aldehydes and amines with TMSCN
in the presence of a catalytic amount of H2SO4=
silicagel afforded the corresponding ꢀ-aminonitriles
in acetonitrile as the solvent in high yields (Scheme 1,
Table 1). The reaction is successful using amines
with a variety of aldehydes, but not with ketones.
These three-component coupling reactions proceeded
efficiently at room temperature with high selectivity.
No cyanohydrin trimethylsilyl ethers (an adduct be-
lonite KSF [16], iodine [17], H14[NaP5W30O110
]
[18], and Fe(ClO4)3 [19]. However, in some cases,
the protocols require tedious work-up leading to
the generation of large amounts of waste. Moreover,
ꢀ
Corresponding author. E-mail: mmh1331@yahoo.com

28
H. A. Oskooie et al.
Scheme 1
Table 1. H2SO4 adsorbed on silica gel catalyzed synthesis of ꢀ-aminonitriles using trimethylsilyl cyanide (TMSCN)
Entry
Aldehyde
Amine
Time=min
Product
mp=ꢁC
Yield=%
Observed
Ref.
1
2
3
4
5
6
7
8
9
Ph–CHO
Ph–CHO
Cl–Ph–CHO
Ph–NH2
furfurylamine
Ph–NH2
furfurylamine
Ph–NH2
Ph–NH2
60
65
90
75
75
60
20
30
60
60
90
1a
1b
1c
1d
1e
1f
1g
1h
1i
70–73
oil
105–108
oil
74–76
92–96
63–72
80–86
oil
73–74 [9]
yellow liq. [9]
109–112 [9]
–
76–78 [9]
94–95 [9]
93
98
96
90
90
92
90
30
96
20
94
Cl–Ph–CHO
4-Me–Ph–CHO
4-MeO–Ph–CHO
4-iPrPh–CHO
4-iPrPh–CHO
4-iPrPh–CHO
4-NO2–Ph–CHO
4-MeO–Ph–CHO
Ph–NH2
–
–
–
–
–
4-Cl–Ph–NH2
furfurylamine
4-Cl–Ph–NH2
4-Cl–Ph–NH2
10
11
1j
1k
oil
71–77
tween an aldehyde and TMSCN were obtained under
these reaction conditions. This is due to the rapid
formation and activation of the imines by H2SO4=
silica gel. The reactions are clean and highly se-
lective affording exclusively ꢀ-aminonitriles in high
yields in a relatively short reaction time. This meth-
od is equally effective with aldehydes bearing elec-
tron withdrawing substituents in the aromatic ring.
In conclusion, we report a simple, convenient, and
practical method for the synthesis of ꢀ-aminonitriles
through a one-pot three-component coupling of alde-
hydes, amines, and TMSCN using H2SO4=silica gel
as the catalyst. The major advantage of this method
is that it is truly a one-pot procedure and that it
does not require a separate step to prepare an imine
for subsequent use. The significant features of this
method include: operational simplicity, inexpensive
reagents, no need for any additive to promote the
reaction, high yields of products, and the use of rel-
atively non-toxic reagents and solvents.
Experimental
General Procedure for the Preparation of ꢀ-Aminonitriles
A mixture of 1 mmol aldehyde, 1 mmol amine, 108 mg TMSCN
(1.1mmol), and 0.5g H2SO4=silica gel in 5 cm3 acetonitrilewas
stirred at room temperature for an appropriate time (Table 1).
After completion of the reaction, as monitored by TLC, the
catalyst was recovered by filteration and 15 cm3 of a 10% soln.
of NaHCO3 were added to the filtrate. Then the organic phase
was separated and dried (MgSO4). Filtration and evaporation of
the solvent gave the ꢀ-aminonitriles as crude products. Further
purification by chromatography (eluent: petroleum ether=ethyl
acetate) afforded ꢀ-aminonitriles in good yields (Table 1).
Adsorbtion of Sulfuric Acid on Silica Gel
A solution of 2 cm3 conc. H2SO4 in 20 cm3 acetone is added to
a dispersion of 100g silica gel (Merk 60, 70–230) in 200cm3

Catalyst for the Synthesis of ꢀ-Aminonitriles
29
acetone and stirred at room temperature for 1 h. The solvent is
removed under reduced pressure. A yellow–brown powder is
obtained, which can be stored in a desiccator for long periods
of times without any appreciable loss of activity.
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2-(Furfurylamino)-2-(4-chlorophenyl)acetonitrile
(1d, C13H11N2ClO)
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IR (KBr): ꢁꢀmax ¼ 3298, 2917, 2840, 2226, 1695, 1580, 1455,
1214, 1131, 1019, 960, 775 cmꢂ1; 1H NMR (CDCl3): ꢂ ¼ 2.30
(brs, 1H, NH), 4.0 (s, 2H), 5.08 (s, 1H), 6.40–6.60 (m, 2H),
6.75–6.90 (d, 2H), 7.40–7.60 (d, 2H) ppm.
[12] De SK (2005) Synth Commun 35: 653
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2-(Phenylamino)-2-(4-isopropylphenyl)acetonitrile
(1g, C17H18N2)
1
IR (KBr): ꢁꢀmax ¼ 3332.0, 3025.13, 2953.0, 2223.52 cmꢂ1; H
NMR (CDCl3): ꢂ ¼ 1.18 (d, 6H), 1.77 (m, 1H), 3.68(d, 1H), 5.25
(d, 1H), 6.68 (d, 2H), 6.76 (t, 1H), 6.9 (d, 2H), 7.1 (d, 2H) ppm.
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4595
2-(4-Chlorophenylamino)-2-(phenyl)acetonitrile
(1h, C14H11N2Cl)
IR (KBr): ꢁꢀmax ¼ 3340.061, 3038.33, 2963.53, 2233.32 cmꢂ1
;
1H NMR (CDCl3): ꢂ ¼ 1.20 (d, 6H), 1.80 (m, 1H), 3.70 (d,
1H), 5.38 (d, 1H), 6.78 (d, 2H), 6.85 (d, 1H), 7.10 (d, 2H), 7.5
(d, 2H) ppm.
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2-(Furfurylamino)-2-(phenyl)acetonitrile (1i, C13H12N2O)
IR (KBr): ꢁꢀmax ¼ 3300, 2920, 2841, 2223, 1681, 1565, 1442,
1214, 1131, 1014, 910, 755 cmꢂ1; 1H NMR (CDCl3): ꢂ ¼ 1.77
(brs, 1H, NH), 3.9 (s, 2H), 4.0 (s, 1H), 6.15–6.35 (m, 2H),
7.0–7.25 (m, 4H) ppm.
2-(4-Chlorophenylamino)-2-(4-nitrophenyl)acetonitrile
(1j, C15H13N2ClO)
IR (KBr): ꢁꢀmax ¼ 3431, 2927, 2869, 2239, 1600, 1517 cmꢂ1
;
1H NMR (CDCl3): ꢂ ¼ 4.07 (d, 1H), 5.39 (d, 1H), 6.70 (d,
2H), 6.90 (d, 2H), 7.20 (d, 2H), 7.47 (d, 2H), 7.9 (m, 2H) ppm.
2-(4-Chlorophenylamino)-2-(4-methoxyphenyl)acetonitrile
(1k, C15H13N2ClO)
[22] a) Heravi MM, Ajami D, Ghassemzadeh M (1999)
Synth Commun 29: 1013; b) Bigdeli MA, Nahid N,
Heravi MM (2000) Iran J Chem Chem Eng 19: 37;
c) Chavez F, Suarez S, Diaz MA (1994) Synth Commun
24: 2325
IR (KBr): ꢁꢀmax ¼ 3380, 3053, 2922, 2241, 1601, 1500, 1451,
1295, 1117, 1041, 925, 762 cmꢂ1; H NMR (CDCl3): ꢂ ¼ 3.80
(s, 3H), 4.0 (d, 1H), 5.30 (d, 1H), 6.8 (d, 2H), 6.90 (d, 2H),
7.25 (d, 2H), 7.50 (d, 2H) ppm; 13C NMR (proton decoupled,
CDCl3): ꢂ ¼ 49.0, 55.8, 113.5, 114.0, 117.9, 119.5, 126.3,
129.0, 129.8, 145.0, 160.1 ppm.
[23] a) Heravi MM, Ajami D, Mojtahedi MM, Tabar Hydar K
(1998) J Chem Res: 620; b) Heravi MM, Kiakoojori R,
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Ajami D (1998) J Chem Res: 718; d) Heravi MM, Ajami
D, Tabar Hydar K (1998) Monatsch Chem 129: 1305;
e) Tajbakhsh M, Heravi MM (1999) Synth Commun
22: 135; f) Mirza Aghyan M, Heravi MM (1999)
Synth Commun 29: 785; g) Heravi MM, Ajami D,
Ghassemzadeh M (1999) Synthesis 3: 393; h) Heravi
MM, Ajami D, Mojtahedi MM, Ghassemzadeh M
(1999) Tetrahedron Lett 40: 561; i) Oskooie HA,
Alimohammadi Z, Heravi MM (2006) Heteroatom
Chem 17: 699; j) Heravi MM, Sabaghian AJ, Bakhtiari
K, Ghassemzadeh M (2006) J Brazil Chem Soc 17: 614;
k) Heravi MM, Tajbakhsh M, Ahmadi AN, Mohajerani B
(2006) Monatsh Chem 137: 175
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