Ferric perchlorate - Catalyzed one-pot synthesis of α-aminonitriles using trimethylsilylcyanide

Article abstract of DOI:10.1080/00397910701462732

A simple and efficient one-pot method has been developed for the synthesis of α-aminonitriles from aldehydes, amines, and trimethylsilyl cyanide in the presence of a catalytic amount of ferric perchlorate. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701462732

Synthetic Communicationsw, 37: 2543–2548, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701462732
Ferric Perchlorate–Catalyzed One-Pot
Synthesis of a-Aminonitriles using
Trimethylsilylcyanide
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
Abstract: A simple and efficient one-pot method has been developed for the synthesis
of a-aminonitriles from aldehydes, amines, and trimethylsilyl cyanide in the presence
of a catalytic amount of ferric perchlorate.
Keywords: aldehydes, amines, a-aminonitriles, ferric perchlorate, trimethylsilyl
cyanide
a-Aminonitriles are important intermediates for the synthesis of a-amino
acids[1] and various nitrogen-containing heterocycles[2] such as imidazoles
and thiadiazoles. They are usually prepared by the nucleophilic addition of
cyanide anion to the imines.[3] The classical Strecker reaction is generally
carried out with alkaline cyanides in aqueous solution. Subsequently,
several modifications of the Strecker reaction have been reported using a
variety of cyanating agents such as a-trimethylsiloxynitriles and diethyl phos-
phorocyanidate under various reaction conditions.[4] The use of trimethylsilyl
cyanide is a safer and more effective cyanide anion source for the nucleophilic
addition reactions of imines under mild conditions.[5] However, many of these
methods involve the use of expensive reagents and extended reaction times,
harsh conditions, and tedious aqueous workup, leading to the generation of
Received in Poland October 6, 2006
Address correspondence to Majid M. Heravi, Department of Chemistry, School of
Sciences, Azzahra University, Vanak, Tehran, Iran. E-mail: mmh1331@yahoo.com
2543

2544
H. A. Oskooie et al.
a large amount of toxic waste. Also, recent one-pot procedures have been
developed for this transformation.[6]
Recently we have reported the ability of ferric perchlorate as catalyst for
transformations in organic syntheses.[7] In continuation of our work to develop
new synthetic methodologies,[8] we herein report that ferric perchlorate, which
acts as a mild Lewis acid, might be a useful and inexpensive catalyst for the
synthesis of a-aminonitrile.
The reaction of aldehydes and amines with trimethylsilylcyanide (TMSCN)
in thepresence ofa catalytic amount offerric perchlorate affordedthecorrespond-
ing a-aminonitriles in acetonitrile as a solvent in high yields (Scheme 1,
Table 1). The reaction is successful using amines with a variety of aldehydes
but not ketones. These three-component coupling reactions proceeded effi-
ciently at ambient temperature with high selectivity. No cyanohydrin tri-
methylsilyl ethers (an adduct between an aldehyde and trimethylsilyl cynide)
were obtained under these reaction conditions. This is because of the rapid
formation and activation of the imines by ferric perchlorate. The reactions are
clean and highly selective, affording exclusively a-aminonitriles in high yields
in a relatively short reaction time. This method is equally effective with
aldehydes bearing electron-withdrawing substituents in the aromatic ring.
In summary, we describe a simple, convenient, and practical method for
the synthesis of a-aminonitriles through a one-pot, three-component coupling
of aldehydes, amines, and trimethylsilyl cyanide using ferric perchlorate. The
major advantage of this method is that it is truly a one-pot procedure that does
not require a separate step to prepare an imine for subsequent use. The signifi-
cant 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 relatively nontoxic reagents and solvents.
EXPERIMENTAL
General Procedure for the Preparation of a-Aminonitriles
A mixture of aldehyde (1 mmol), amine (1 mmol), trimethylsilyl cyanide
(1.1 mmol), and Fe(ClO4)3 (0.1 mmol, 0.05 g) in acetonitrile (5 mL) was
stirred at room temperature for an appropriate time (Table 1). After com-
pletion of the reaction, as monitored by thin-layer chromatography (TLC), a
Scheme 1.

Table 1. Ferric perchlorate–promoted synthesis of a-aminonitriles using trimethylsilyl cyanide
Mp (8C)
Entry
Aldehyde
Benzaldehyde
Benzaldehyde
Amine
Aniline
Time (h)
Observed
Found
Yield (%)
1
2
3.0
3.0
4.0
2.5
2.0
5.0
70–73
Oil
73–74[9]
95
83
94
95
70
90
80
92
88
96
83
94
97
85
80
91
86
Furfurylamine
Aniline
Yellow liq.[9]
3
4-Chlorobenzaldehyde
4-Chlorobenzaldehyde
4-Chlorobenzaldehyde
2- Chlorobenzaldehyde
2- Chlorobenzaldehyde
4-Methyl benzaldehyde
4-Methyl benzaldehyde
4-Methoxybenzaldehyde
2-Ethoxybenzaldehyde
4-Isoprpylbenzaldehyde
4-Isoprpylbenzaldehyde
4-Nitrobenzaldehyde
4-Nitrobenzaldehyde
2-Naphtaldehyde
105–108
90–102
Oil
109–112[9]
—
4
4-Chloroaniline
Furfurylamine
4-Chloroaniline
Aniline
5
—
—
6
95–100
150–158
74–76
103–110
92–96
Oil
7
—
76–78[9]
—
94–95[9]
Yellow liq.[9]
8
Aniline
4-Chloroaniline
Aniline
4.0
4.0
3.0
3.0
3.0
2.5
5.0
6.0
5.0
4.0
9
10
11
12
13
14
15
16
17
Furfurylamine
Aniline
63–72
Oil
Oil
—
—
—
—
—
—
Furfurylamine
Furfurylamine
4-Chloroaniline
4-chloroanilin
4-chloroanilin
160–200
115–120
71–77
4-Methoxybenzaldehyde

2546
H. A. Oskooie et al.
10% NaHCO3 solution (15 mL) was added. Workup and purification over
silica gel gave the corresponding a-aminonitriles in high yields.
Spectral Data for Selected Compounds
2-(N-Anilino)-2-(4-chlorophenyl)acetonitrile (entry 3). 1H NMR (300 MHz,
CDCl3) d 4.01 (br s, 1H), 5.39 s, 1H), 6.75 (d, J ¼ 8 Hz, 2H), 6.91
(t, J ¼ 7.8 Hz, 1H), 7.15 (t, J ¼ 7.9 Hz, 2H), 7.38 (d, J ¼ 7.8 Hz, 2H), 7.61
(d, J ¼ 8 Hz, 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 (M þ ), 149,
114, 91, 77, 59.
1
2-(N-furfurylamino)-2-phenylacetonitrile (entry 2). H NMR (300 MHz,
CDCl3) 1.82 (br s, 1H), 4.01 (s, 2H), 4.79 (s, 1H), 6.21–6.41 (m, 2H),
7.31–7.56 (m, 6H); EIMS m/z 212 (M þ), 186, 81, 77.
REFERENCES
1. Shafran, Y. M.; Bakulev, V. A.; Mokrushin, V. S. Synthesis and properties of
a-Aminonitriles. Russ. Chem. Rev. 1989, 58, 148.
2. (a) Weinstock, L. M.; Davis, P.; Handelsman, B.; Tull, R. A general synthetic
system for 1,2,5-thiadiazoles. J. Org. Chem. 1967, 32, 2823; (b) Matier, W. L.;
Owens, D. A.; Comer, W. T.; Deitchman, D.; Ferguson, H. C.;
Seidehamel, R. J.; Young, J. Antihypertensive agent: Synthesis and biological
properties of 2-amino-4-aryl-2-imidazolines. J. Med. Chem. 1973, 16, 901.
3. (a) Strecker, A. General catalyst for the asymmetric Strecker reaction. Ann. Chem.
Pharm. 1850, 75, 27; (b) Mai, K.; Patil, G. Facile synthesis of aminonitriles. Tetra-
hedron Lett. 1984, 25, 4583; (c) Harusawa, S.; Hamada, Y.; Shioiri, T. Diethyl
phosphorocyanidated (DEPC): A novel reagent for the classical Strecker’s
a-amino nitrile synthesis. Tetrahedron Lett. 1979, 20, 4663.
4. (a) Mai, K.; Patil, G. Facile synthesis of aminonitriles. Tetrahedron Lett. 1984, 25,
4583; (b) Harusawa, S.; Hamada, Y.; Shioiri, T. Diethyl phosphorocyanidated
(DEPC): A novel reagent for the classical Strecker’s a-amino nitrile synthesis.
Tetrahedron Lett. 1979, 20, 4663.
5. (a) Chakraborty, T. K.; Reddy, G. V.; Hussain, K. A. Diastereoselective Strecker
synthesis using a-phenylglycinol as chiral auxiliary. Tetrahedron Lett. 1991, 32,
7597; (b) Leblanc, J.; Gibson, H. W. Synthesis of a-aminonitriles by self-
catalyzed, stoichiometric reaction of primary amines, aldehydes, and trimethylsily
cyanide. Tetrahedron Lett. 1992, 33, 6295; (c) Heydari, A.; Fatemi, P.;
Alizadeh, A. Lithium perchlorate/diethylether–catalyzed aminocyanation of
aldehydes. Tetrahedron Lett. 1998, 39, 3049.
6. (a) Kobayashi, S.; Ishitani, H.; Ueno, M. Facile synthesis of a-amino nitriles using
lanthanide triflate as a Lewis acid catalyst. Synlett 1997, 115; (b) Kobayashi, S.;
Busujima, T.; Nagayama, S. Scandium triflate–catalyzed Strecker-type reactions
of aldehydes, amines, and tributyltin cyanide in both organic and aqueous
solutions: Achievement of complete recovery of the tin compounds toward

One-Pot Synthesis of a-Aminonitriles
2547
environmentally friendly chemical. J. Chem. Soc., Chem. Commun. 1998, 981;
(c) Subba Reddy, B. V.; Eeshwaraiah, B.; Srinivas, M. Montmorillonite KSF
clay catalyzed one-pot synthesis of a-aminonitriles. Tetrahedron 2004, 60,
1767–1771; (d) De, S. K.; Gibbs, R. A. Bismuth trichloride catalyzed synthesis
of a-aminonitriles. Tetrahedron Lett. 2004, 45, 7407–7408; (e) De, S. K.
Nickel(II) chloride catalyzed one-pot synthesis of a-aminonitriles. J. Mol. Cata.
A: Chem. 2005, 225, 169–171; (f) Ranu, B. C.; Dey, S. S.; Hajra, A. Indium tri-
chloride catalyzed one-step synthesis of a-amino nitriles by a three-component
condensation of carbonyl compounds, amines and potassium cyanide. Tetrahedron
´
´
2002, 58, 2529–2532; (g) Martınez, R.; Ramo, D. J.; Yus, M. Catalyst-free multi-
component Strecker reaction in acetonitrile. Tetrahedron Lett. 2005, 46,
8471–8474.
7. (a) Heravi, M. M.; Behbahani, F. K.; Oskooie, H. A.; Hekmatshoar, R. Mild and
efficient tetrahydropyranylation of alcohols and dehydropyranylation of THP
ethers catalyzed by ferric perchlorate. Tetrahedron Lett. 2005, 46, 2543–2545;
(b) Heravi, M. M.; Behbahani, F. K.; Oskooie, H. A.; Hekmatshoar, R. Catalytic
aromatization of Hantzsch 1,4-dihydropyridines by ferric perchlorate in acetic
acid. Tetrahedron Lett. 2005, 46, 2775–2777; (c) Heravi, M. M.;
Behbahani, F. K.; Oskooie, H. A.; Hekmatshoar, R. Ferric perchlorate: A novel
and highly efficient catalyst for direct acetylation of THP ethers with acetic
acid. J. Mol. Cat. A: Chem. 2006, 244, 8–10; (d) Heravi, M. M.;
Behbahani, F. K.; HekmatShoar, R.; Oskooie, H. A. Catalytic acetylation of
alcohols and phenols with ferric perchlorate in acetic acid. Catal. Commun.
2006, 7, 136–139; (e) Heravi, M. M.; Behbahani, F. K.; Oskooie, H. A.;
Hekmatshoar, R. Ferric perchlorate catalyzed one-pot synthesis of 3,4-dihydropyr-
imidin-2(1H)-Ones and thiones: An expedient protocol for the Biginelli reaction.
Mendeleev Commun. Submitted.
8. (a) Bamoharram, F. F.; Heravi, M. M.; Roshani, M.; Gharib, A.; Jahangir, M.
Preyssler catalyst [NaP5W30O110]
142: A green, efficient and reusable catalyst for
esterification of salicylic acid with aliphatic and benzylic alcohols. Appl. Cata.
2006, 302, 42; (b) Heravi, M. M.; Hekmatshoar, R.; Pedram, L. Synthesis of
N-arylphthalimides catalyzed by 1,4-diazabicyclo[2,2,2]octane [DABCO] in sol-
ventless system. J. Mol. Catal. A: Chem. 2005, 231, 89; (c) Asadolah, K.;
Heravi, M. M. Bismuth (III) nitrate supported onto silica gel, a new catalyst for
acetylation of alcohols and phenols under microwave irradiation. Phosphorus,
Sulfur Silicon Relat. Elem. 2004, 179, 2335–2339; (d) Bigdeli, M. M.;
Nahid, M. A.; Ajami, D. Sulphuric acid adsorbed on silica gel: An efficient
catalyst for the protection and deprotection of alcohols with dihydropyran.
Indian. J. Chem. Sect. 1999, 38, 1285–1286; (e) Heravi, M. M.; Bakhtiari, K.;
Bamoharram, F. F. 12-Molybdophosphoric acid: A recyclable catalyst for the
synthesis of Biginelli-type 3,4-dihydropyrimidine-2(1H)-ones. Catal. Commun.
2006, 7, 373; (f) Bamoharram, F. F.; Heravi, M. M.; Roshani, M.; Gharib, A.;
Jahangir, M. A catalytic method for synthesis of g-butyrolactone, 1-caprolactone
and 2-cumaranone in the presence of Preyssler’s anion, [NaP5W30O110]
142, as a
green and reusable catalyst. J. Mol. Catal. A: Chem. 2006, 252, 90;
(g) Bamoharram, F. F.; Heravi, M. M.; Roshani, M.; Tavakoli, N. N-oxidation
of pyridine carboxylic acids using hydrogen peroxide catalyzed by a green hetero-
polyacid catalyst: Preyssler’s anion, [NaP5W30O110]14. J. Mol. Catal. A: Chem.
2006, 252, 219; (h) Tajbakhsh, M.; Heravi, M. M.; Mohajerani, B.;
Ahmadi, A. N. Natural HEU type zeolite catalyzed Biginelli reaction for the
synthesis of 3,4-dihydropyrimidin-2(1H) one derivatives. J. Mol. Catal. A:

2548
H. A. Oskooie et al.
Chem. 2005, 236, 213; (i) Heravi, M. M.; Motamedi, R.; Siefi, N.;
Bamoharram, F. F. Catalytic synthesis of 6-aryl-1H-pyrazolo[3,4-d]pyrimidin-
4[5H]-ones by heteropolyacid: H14[NaP5W30O110] and H3PW12O40. J. Mol.
Catal. 2006, 249, 1; (j) Oskooie, H. A.; Heravi, M. M.; Bakhtiari, K.;
Zadsirjan, V.; Bamoharram, F. F. H14[NaP5W30O110] as an efficient catalyst for
the one-pot synthesis of a-amino nitriles. Synlett 2006, 1768–1770.
9. Yadav, J. S.; Subba Reddy, B. V.; Eeshwaraiah, B.; Srinivas, M. Montmorillonite
KSF clay catalyzed one-pot synthesis of a-aminonitriles. Tetrahedron 2004, 60,
1767–1771.