Simple route to ferrcenyl(alkyl)imidazoles

Article abstract of DOI:10.1016/S0022-328X(02)02038-7

A suitable method for the synthesis of ferrocenyl(alkyl)imidazoles is proposed. The treatment of α-ferrocenylcarbinols with N,N′-carbonyldiimidazole affords the title compounds, are in more than 80% yields.

Full text of DOI:10.1016/S0022-328X(02)02038-7

Journal of Organometallic Chemistry 665 (2003) 13Á14
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www.elsevier.com/locate/jorganchem
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Simple route to ferrocenyl(alkyl)imidazoles
Alexander A. Simenel, Elena A. Morozova, Yulia V. Kuzmenko, Lubov’ V. Snegur *
A.N. Nesmeyanov Institute of Organo-Element Compounds, Academy of Sciences of Russia, 28 Vavilov St., 11991 Moscow, Russian Federation
Received 19 April 2002; accepted 15 October 2002
Abstract
A suitable method for the synthesis of ferrocenyl(alkyl)imidazoles is proposed. The treatment of a-ferrocenylcarbinols with N,N?-
carbonyldiimidazole affords the title compounds, are in more than 80% yields.
# 2002 Published by Elsevier Science B.V.
Keywords: Ferrocene derivatives of azoles; a-Ferrocenylalkylation; Imidazole; N,N?-Carbonyldiimidazole
1. Results and discussion
cenylalkylating agent in water at 100 8C we obtained a
mixture of mono- and bis-ferrocenylmethyl derivatives
of imidazole, ( yields 30 and 15%, respectively) [9]. Other
ferrocenyl(alkyl)ammonium salts are unstable and their
synthesis is difficult [10]. Therefore, the homologues
The acid-catalyzed ferrocenylalkylation reaction
using a-ferrocenylcarbinols in aqueous-organic is one
of the most convenient methods for introducing ferro-
cenylalkyl groups into various nucleophilic substrates
[1]. The ferrocenyl(alkyl)azoles FcCH(R)Az and the
salts of azoles [(FcCHR)2Az]ꢀBF4ꢁ were synthesized
(Fc, ferrocenyl; AzH, pyrazoles, polyfluoro benzimida-
FcCH(R)Im (RꢂMe, Et and so on) were not prepared.
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In the present work we propose a new method for the
introducing of imidazolyl groups into ferrocenylalkyl
compounds by the ferrocenylalkylation reaction of
N,N?-carbonyldiimidazole. The mixture of equimolar
amounts of ferrocenylcarbinols and N,N?-carbonyldii-
midazole in methylene dichloride was boiled for 1 h. 1N-
Ferrocenyl(alkyl)imidazoles were synthesized in high
yields. We are planning to investigate these compounds
as biologically active components.
zoles, triazoles, benzotriazoles) [2Á4] in this way. Some
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of these compounds were found to exhibit antitumor
activity [5,6]. The ferrocene derivatives of benzimida-
zoles are also of interest as ligands in metal complexes
for catalysis [7].
However, under acidic conditions ferrocenylalkyla-
tion of imidazole was not realized because of the
protonation of his N-basic center (basic pKa 7.00). At
the same time imidazole is actually one of the most
significant heterocycles in biology. Therefore, it was
important to synthesize its ferrocene derivatives in order
to study potential ferrocene containing drugs.
Earlier the ferrocenyl(ethyl)imidazole FcCH(CH3)Im
was obtained from the reaction between ferroceny-
l(ethyl)benzotriazole FcCH(CH3)BTr and imidazole in
methanol under acidic conditions (CH3COOH or HCl)
in lowish yields (30%) [8]. Using trimethylferroce-
nyl(methyl)ammonium iodide FcCH2NMe3I as a ferro-
It is important to note, that this simple procedure
allows us to realize the ferrocenylalkylation reaction of
N,N?-carbonyldiimidazole selectively. Actually 1N-fer-
rocenyl(alkyl)imidazole was the only product formed.
* Corresponding author
E-mail address: snegur@ineos.ac.ru (L.V. Snegur).
0022-328X/02/$ - see front matter # 2002 Published by Elsevier Science B.V.
PII: S 0 0 2 2 - 3 2 8 X ( 0 2 ) 0 2 0 3 8 - 7

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A.A. Simenel et al. / Journal of Organometallic Chemistry 665 (2003) 13Á14
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2. Experimental
4.92 (t, 1H, CH); 6.89 (s, 1H, CH); 7.01 (s, 1H, CH);
7.52 (s, 1H, CH).
1H-NMR spectra were obtained on ‘Bruker-200-WP’.
Mass spectra were measured on ‘Kratos MS-890’
spectrometer (ionizing strain 70 eV), IR spectra were
recorded on IR-20 spectrometer (Karl Zeiss).
Dichloromethane was dried over CaCl2. N,N?-Car-
bonyldiimidazole (CDI) was purchased from Lancaster
and used without purification. Ferrocenylmetanol 1a
was obtained from trimethylferrocenylmethylammo-
nium iodide [11], carbinols 1b, c, d were received by
acylation of ferrocene by corresponding acid chlorides
[12] with the subsequent reduction by lithium aluminium
hydride in diethyl ether [3,13], 2-ferrocenyl-2-hydroxy-
2.5. Ferrocenyl(benzyl)imidazole (2d)
Yield: 82%. Yellow crystals, m.p. 91Á
(%): 342 (75) [M]ꢀ. IR (KBr, n, cmꢁ1): 3111, 2944,
2872, 1518, 1472, 1140, 1123, 1015, 927, 840, 740Á710.
1H-NMR (CDCl3, d, ppm): 4.10Á
4.25 (m, 9H, Fc); 6.15
(s, 1H, CH); 6.82 (s, 1H, CH); 7.05 (s, 1H, CH); 7.14Á
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92 8C, MS m/z
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7.30 (m, 5H, Ph); 7.45 (s, 1H, CH).
2.6. Ferrocenyl(iso-propyl)imidazole (2e)
propane 1e*by reaction of ferrocene with acetone in
sulfuric acid [14].
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Yield: 80%. Yellow crystals, m.p. 104Á105 8C, MS m/
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z (%): 294 (23) [M]ꢀ. IR (KBr, n, cmꢁ1): 3118, 3090,
3011, 1510, 1482, 1398, 1380, 1281, 1215, 1116, 1087,
1010, 910, 850, 830Á
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815, 724, 510, 482. 1H-NMR
2.1. General procedure
(CDCl3, d, ppm): 1.45 (s, 6H, CH3), 4.10Á
9H, Fc); 6.89 (s, 1H, CH); 6.93 (s, 1H, CH); 7.38 (s, 1H,
CH).
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4.19 (m,
The mixture of equimolar amounts of ferrocenylcar-
binol and N,N?-carbonyldiimidazole in anhydrous
CH2Cl2 was refluxed for 1 h. The resulting mass was
cooled, 50 ml ether was added and then flushed by 20%
solution of phosphoric acid (2ꢃ
phase was alkalized up to pH 5 and then extracted by
CH2Cl2 (2ꢃ50 ml). An organic layer was dried over
anhydrous sodium sulphate. Solvents were removed in
vacuo. The resulting product was dried over CaCl2.
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50 ml). An aqueous
Acknowledgements
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This work has been partially supported by The
Scientific Training Center of Biomedical Chemistry
(Grant No A0078, the Federal Target Program ‘Inte-
gration’).
2.2. Ferrocenyl(methyl)imidazole (2a)
Yield: 80%. Yellow crystals, m.p. 65 8C, MS m/z
(relative intensity, %): 266 (100) [M]ꢀ. IR (KBr, n,
References
cmꢁ1): 3150Á
/
2970, 1690Á
/
1520, 1450, 1220Á
/
1100, 1110Á
/
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1
1000, 830, 491. H-NMR (CDCl3, d, ppm): 4.15Á
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4.12
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m/z (%): 280 (38) [M]ꢀ. IR (KBr, n, cmꢁ1): 3118, 2992,
2940, 2868, 1671, 1510, 1415Á1390, 1240, 1115, 1090,
1010, 923, 840, 754, 641. H-NMR (CDCl3, d, ppm):
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orange crystals, m.p. 75Á76 8C, MS
/
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CH); 7.44 (s, 1H, CH).
2.4. Ferrocenyl(butyl)imidazole (2c)
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Yield: 78%. Dark brown oil, MS m/z (%): 308 (100)
[M]ꢀ. IR (KBr, n, cmꢁ1): 3109, 2972, 2885, 1692, 1511,
1425, 1292, 1174, 1118, 1090, 1040Á
1H-NMR (CDCl3, d, ppm): 0.93 (m, 3H, CH3); 1.15 (m,
2H, CH2); 2.00 (m, 2H, CH2); 4.05Á4.15 (m, 9H, Fc);
/1020, 923, 835, 754.
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