Lithium perchlorate suspend in methylene chloride, a mild, efficient and reusable catalyst for the synthesis of ferrocene aminonitrile derivatives

Article abstract of DOI:10.1016/j.jorganchem.2004.08.030

A practical and efficient method for the synthesis of α-aminonitriles of ferrocene by one-pot three-component reaction of ferrocenecarboxaldehyde, trimethylsilyl cyanide and amines catalyzed by lithium perchlorate suspend in CH₂Cl₂ is reported under mild and neutral reaction conditions in high yields and short reactions times.

Full text of DOI:10.1016/j.jorganchem.2004.08.030

Journal of Organometallic Chemistry 690 (2005) 76–78
www.elsevier.com/locate/jorganchem
Lithium perchlorate suspend in methylene chloride, a mild,
efficient and reusable catalyst for the synthesis of ferrocene
aminonitrile derivatives
*
Rozbeh Yousefi, Najmedin Azizi, Mohammad R. Saidi
Depatment of Chemistry, Sharif University of Technologhy, P.O. Box 11365-9516, Tehran 11365, Iran
Received 12 July 2004; accepted 18 August 2004
Available online 25 September 2004
Abstract
A practical and efficient method for the synthesis of a-aminonitriles of ferrocene by one-pot three-component reaction of ferr-
ocenecarboxaldehyde, trimethylsilyl cyanide and amines catalyzed by lithium perchlorate suspend in CH2Cl2 is reported under mild
and neutral reaction conditions in high yields and short reactions times.
ꢀ 2004 Elsevier B.V. All rights reserved.
Keywords: Trimethylsilyl cyanide; Ferrocenecarboxaldehyde; Lithium perchlorate, a-Aminonitriles of ferrocene
1. Introduction
azoles, imidazoles, etc. with biological activities [7].
Moreover, a-aminonitriles derived from ferrocenecar-
boxaldehyde are used as chiral auxiliaries in some asym-
metric syntheses such as the Ugi four-component
condensation reaction, and the potential of these com-
pounds as new types of ligands has been reported re-
cently in copper-catalyzed reaction [8–10].
The classical Strecker reaction is generally carried out
with alkaline cyanides in aqueous solution which have
some limitations. Thus, several modifications of the
Strecker reaction have been reported using a variety of
cyanating agent such as a-trimethylsiloxynitriles and
diethyl phosphorocyanidete under various reaction con-
ditions [11]. Trimethylsilylcyanide (TMSCN) is a cya-
nide anion source, which provides promising and safer
routes to these compounds [12]. There are two common
reported methods for the synthesis of aminonitriles of
ferrocene in the literature; nucleophilic displacement of
acetate with methanolic amines in the corresponding
acetoxy ferrocenylacetonitriles and one-pot reaction
of ferrocene-carboxaldehyde, NaHSO3, NaCN and
amines. However, the reported procedures have long
The Mannich reaction provides an excellent method
for carbon–carbon bond formation and its importance
were reflected in the ever-increasing number of suitable
substrate and reaction conditions, which have been
developed since long ago [1]. Several important experi-
mental modifications of Mannich reaction have been re-
ported in the past decade, which involve the use of
preformed iminium salts [2]. The preformed iminium
salts can be prepared by a number of different methods,
including the reaction of acetyl chloride with aminals [3],
trifluroacetic anhydride with N-oxides [4] and trichloro-
methylsilane with aminal and aminol ethers [5].
The Strecker reaction provides one of the most effi-
cient methods for the synthesis of a-aminonitriles, which
are useful intermediates in the synthesis of amino acids
[6] and nitrogen containing heterocycles, such as thiadi-
*
Corresponding author. Tel.: +98 21 600 5718; fax: +98 21 601
2983.
E-mail address: saidi@sharif.edu (M.R. Saidi).
0022-328X/$ - see front matter ꢀ 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2004.08.030

R. Yousefi et al. / Journal of Organometallic Chemistry 690 (2005) 76–78
77
Table 1
a-Aminonitriles derived from ferrocenecarboxaldehyde
reaction time, tedious work up conditions and low yields
in the latter case [9].
Therefore, the development of novel and practical
method for the cyanation under mild conditions has at-
tracted much attention in organic synthesis.
N H
H
N
N
O
N
N
NR2
N
4a
4b
4c
4d
4e
100
4f
98
Yields
Recently, concentrated solutions of LiClO4 in diethyl
ether (LPDE) have been used in various organic trans-
formation [13,14]. On the other hand, a catalytic amount
of LiClO4 suspended in dichloromethane has also been
reported to provide a mild and effective medium for some
well-known reactions, such as Mannich, Mukaiyama al-
dol, or Diels–Alder reactions [15]. In this paper, a much
more simple, general and new catalytic route for the syn-
thesis of a-aminonitriles of ferrocene via one-pot three
component reactions of amine, ferrocenecarboxaldehyde
and trimethylsilylcyanide in dichloromethane in the pres-
ence of catalytic amount of LiClO4 is described.
100
98
100
100
H
H
H
N
N H
N H
H
NR2
N
N
N
4j
95
4k
(S)- 98b
4l
(R)- 98b
4g
4h
4i
93a
96
Yields
95
a
Reaction time 80 min.
de 100:0 (measured by NMR).
b
2. Experimental
2.1. General
In the first step, we used catalytic amount of LiClO4
in a range of different solvents at room temperature.
Among the solvents examined (acetonitrile, dichloro-
methane, acetone, toluene and petroleum ether), CH2Cl2
gave the best result. Concentrated solution of LPDE (ca.
5 M) also gave the corresponding a-aminonitriles of fer-
rocene in good yields, but preparation and handling of 5
M LiClO4 solution in ether is an inherent disadvantage
of such a reaction. Optimum conditions found to be 2
equivalent of LiClO4 in CH2Cl2 as solvent. With these
results in hand, addition of TMSCN in the present of
catalytic amount of LiClO4 to other iminium salts or
imines, prepared in situ, were studied using the optimal
reaction conditions, Scheme 1. In all cases, a nearly
quantitative conversion of the iminium salts or imines
to the corresponding a-aminonitriles of ferrocene was
observed. The reactions are clean and highly selective
for affording exclusively a-aminonitriles of ferrocene in
high yields and short time. The reaction conditions are
mild enough to perform these reactions in the presence
of either acid or base sensitive functional groups. Fur-
thermore, this method is equally effective for the aro-
matic, aliphatic, hindered, and unhindered amines. The
yields of products were not affected by the nature of
amines. A summary of the results is shown in Table 1.
In conclusion, this method has the advantages of
inexpensive reagents, simple operation, improved yields,
enhanced rates and simple experimental work up
procedures.
IR spectra were taken on Matt Son 1000 Unicam
FTIR, 1H and 13C NMR spectra were recorded on Bru-
ker 500 MHz Ultra Shield. All reactions were performed
under argon. Dichloromethane was refluxed and dis-
tilled over phosphorus pentoxide. Column chromatog-
raphy was performed on Merck silica gel 60.
Chemicals were purchased from Fluka, Merck, and used
as received.
2.2. General procedure
The ferrocencarboxaldehyde (0.5 mmol), LiClO4 (1
mmol) and CH2Cl2 (3 mL) were placed in a 50 mL flask
and stirred for 3 min, then an amine (0.8 mmol) were
added via syringe, after 5 min, TMSCN (0.7 mmol)
was added and the mixture was stirred at r.t. for about
20–30 min, after the completion of the reaction, CH2Cl2
(10 mL) was added, and lithium perchlorate was filtered
off. Then the organic layer washed with aqueous NaH-
CO3 (2 · 10 mL), water (2 · 10 mL), and dried over
Na2SO4. The reaction product was recovered by simple
removal of solvent and purified by column chromatog-
raphy on silica gel, eluting with petroleum ether/EtOAc,
if necessary. All compounds were characterized on the
basis of their spectroscopic data (IR, NMR), and by
comparison with those reported in the literature [9,10].
2.2.1. Caution
Although we did not have any accident while using
LiClO4, it is advisable to dry lithium perchlorate in a
fume hood using a suitable lab-shield.
NR2
CN
O
H
LiClO4
2.2.2. Spectroscopic data
Fe
Fe
+
(CH3)3SiCN
R2NH
+
4k: d 1.47 (d, J = 6.4 Hz, 3H), 1.87 (br, NH), 4.09–
4.50 (m, 11H), 7.30–7.46 (m, 5H); 4l: d 1.47 (d, J = 6.5
Hz, 3H), 1.61 (br, NH), 4.09–4.46 (m, 11H), 7.30–7.45
(m, 5H).
CH2Cl2 r. t.
1
2
4
3
Scheme 1.

78
R. Yousefi et al. / Journal of Organometallic Chemistry 690 (2005) 76–78
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Chem. 32 (1967) 2823.
Acknowledgement
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(c) M. Sawamura, Y. Ito, Chem. Rev. 92 (1992) 857.
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58 (1989) 148.
We are grateful to Volkswagen-Stiftung (I/78849)
Federal Republic of Germany, for financial support to-
wards the purchase of equipments and chemicals.
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