Synthesis and properties of 5-ferrocenyl-1H-pyrazole-3-carbaldehydes

Article abstract of DOI:10.1016/j.jorganchem.2010.11.018

New ferrocene derivatives - ethyl esters of 1-aryl-5-ferrocenyl-1H- pyrazole-3-carboxylic acids were synthesized. The corresponding aldehydes were obtained from acid esters in two steps. The reductive amination reaction of 5-ferrocenyl-1-phenyl-1H-pyrazole-3-carbaldehyde was studied. Several of these compounds were investigated by cyclic voltammetry. All of them exhibited a reversible one-electron oxidation-reduction wave owing to the ferrocene-ferricinium redox couple with a positive shift (0.51-0.69 V) compared with that of ferrocene (0.46 V). The X-ray crystal structure of the ethyl ether 1-(3-chloro-2-fluorophenyl)-5-ferrocenyl-1H-pyrazole-3-carboxylic acid is also presented.

Full text of DOI:10.1016/j.jorganchem.2010.11.018

Journal of Organometallic Chemistry 696 (2011) 2108e2115
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Synthesis and properties of 5-ferrocenyl-1H-pyrazole-3-carbaldehydes
,
a,
Alexey N. Rodionov a , Alexander A. Simenel b, Alexander A. Korlyukova, Vadim V. Kachala c,
*
Svetlana M. Peregudova a, Kira Ya. Zherebker a, Elena Yu. Osipova a
a A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 28 Vavilov St., 119991 GSP-1 Moscow, Russian Federation
b Moscow State Mining University, 6 Leninsky Ave., Moscow 119991, Russian Federation
c N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky Ave., 119991 Moscow, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
New ferrocene derivatives e ethyl esters of 1-aryl-5-ferrocenyl-1H-pyrazole-3-carboxylic acids were synthe-
sized. The corresponding aldehydes were obtained from acid esters in two steps. The reductive amination
reaction of 5-ferrocenyl-1-phenyl-1H-pyrazole-3-carbaldehydewasstudied.Severalofthesecompoundswere
investigated by cyclic voltammetry. All of them exhibited a reversible one-electron oxidationereduction wave
owing to the ferroceneeferricinium redox couple with a positive shift (0.51e0.69 V) compared with that of
ferrocene (0.46 V). The X-ray crystal structure of the ethyl ether 1-(3-chloro-2-fluorophenyl)-5-ferrocenyl-1H-
pyrazole-3-carboxylic acid is also presented.
Received 24 May 2010
Received in revised form
31 October 2010
Accepted 12 November 2010
Keywords:
Ferrocene
Pyrazoles
Ó 2010 Elsevier B.V. All rights reserved.
Reductive amination
Cyclic voltammetry
X-ray structure determination
1. Introduction
[1,5-a]pyrazin-4(5H)-one derivatives demonstrated antitumor
ꢀ
ꢀ
activity [3]. Besides, Vukicevic et al. showed that FPCA derivatives of
the amino acids (especially those containing heteroaromatic rings
such as histidine and tryptophan) appeared to be the most active
against myelogenous leukemia K562 cell lines with a better cytotoxic
potential than the starting FPCA precursor [4].
Ferrocene-heterocyclic compounds are of great interest both as
exhibiting biological activity and as ligands for asymmetric catal-
ysis. Earlier, heterocyclic ferrocene-containing compounds were
shown to exhibit a wide range of biological activities such as
antianemic, antibacterial, antitumor, and fungicidal ones [1e4].
Besides, ligands having ferrocenylheterocyclic moieties are suitable
for the reactions of hydration, allylation, silylation, cyanation and
many others [5,6].
The including of pyrazoles as key motifs in biologically active
compounds has grown rapidly in the past decade. Both the phar-
maceutical and agrochemical industries employ them as the central
building blocks for the synthesis of compound libraries. At present,
commercial drugs on the base of pyrazole are widely used in the
clinical practice, e.g., sildenaphyl (ViagraÔ), phenybutasole (an
antiphlogistic drug), or herbicidal diphenzoquat.
Therefore, the purpose of this study was the development of the
method for synthesis of isomeric ferrocenylpyrazolecarbaldehydes
and investigation of their reactivity in the reaction of direct reductive
amination. In the present paper we report the obtainment of
N-substituted 5-ferrocenyl-1-aryl-1H-pyrazole-3-aldehydes and the
corresponding ethyl carboxylates, the cyclic voltammetry study of
several compounds synthesized and X-ray determination of the
molecular structure of ethyl ether 1-(3-chloro-2-fluorophenyl)-5-
ferrocenyl-1H-pyrazole-3-carboxylic acid.
2. Results and discussion
Recently, it was shown that the derivatives of 3-ferrocenyl-1-
phenyl-1H-pyrazole-4-carbaldehyde (FPCA), i.e. the products of
reductive amination by different amines (especially tret-butilamine
and cyclohexylamine) exhibited antimicrobial activity comparable
with amikacin and tetracycline [2] in tests on a wide range of
microorganisms, whereas 5-alkyl-2-ferrocenyl-6,7-dihydropyrazolo
2.1. Synthesis of ethyl esters of 5-ferrocenyl-1H-azole-3-carboxylic
acids
The condensation of 1,3-dicarbonyl compounds and hydrazine
or monosubstituted hydrazines is known to be the most suitable
method for the synthesis of pyrazole ring. Ethyl ester of ferroce-
noylpyruvic acid was used as the starting materials. The Claisen
condensation of acetylferrocene (1) and diethyl oxalate in the
* Corresponding author.
E-mail address: rodalex@ineos.ac.ru (A.N. Rodionov).
0022-328X/$ e see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2010.11.018

A.N. Rodionov et al. / Journal of Organometallic Chemistry 696 (2011) 2108e2115
2109
presence of NaOEt was reported to furnish ethyl 2,4-dioxo-4-fer-
rocenylbutanoate (2) (52%) [7]. To choose a base e solvent system
providing the best results we have tested several reaction systems
(Scheme 1). In general, it turned out that the reactions produced
the corresponding product in good yields in almost all tested base
systems.
The use of potassium tert-butoxide in benzene allows a facile
isolation and purification of the intermediate potassium salt of
ethyl 2,4-dioxo-4-ferrocenylbutanoate. Addition of an equimolar
amount of acetic acid to the suspension of salt in CH2Cl2 eliminated
the free ester (89% overall yield). The presence of a broad singlet at
15 ppm (OH proton) and a singlet (1H) at 6.54 ppm in the 1H NMR
spectrum recorded in CDCl3 solution at room temperature proves
that the ester 2 exists entirely in enol form.
on 1H NMR-data), with ethyl ester 5-ferrocenyl-1-methyl-3-pyr-
azole carboxylic acid 3k being the major one (Scheme 3). Crystal-
lization from ethanol-chloroform mixture (50/1) repeated twice
allowed us to separate 3k in analytically pure form. The reaction of
2 and methyl hydrazine in glacial acetic acid leads to the formation
of ethyl ester 5-ferrocenyl-1-methyl-3-pyrazole carboxylic acid 3k
in 85% yield; its structure was assigned on the basis of 1H and 13C
NMR spectra, and 1H/13
correlations.
C (HSQC and HMBC) heteronuclear
2.2. Synthesis of aldehydes
The corresponding alcohols were obtained in 90e95% yields by
reduction of esters 3aek with LiAlH4 in a THF-1,4-dioxane mixture.
Esters of 5-ferrocenyl-1-aryl-1H-pyrazole-3-carboxylic acids
were synthesized in high to quantitative yields by the condensation
between ethyl 2,4-dioxo-4-ferrocenylbutanoate 2 (enol form) and
monosubstituted arylhydrazines. Noteworthy, the reaction with
catalytic amounts of acetic acid in boiling ethanol affords one
isomer only (Scheme 2). The structures of compounds were
assigned on the basis of 1H and 13C NMR spectra, 1H/13C hetero-
nuclear correlations, and NOE-experiments. The coupling of ethyl
esters of acetyl- or benzoylpyruvic acid with monoarylhydrazine
yields pyrazoles with the same arrangement of substituents in the
heterocyclic fragment [8e10].
(5-Ferrocenyl-1-phenyl-1H-pyrazol-3-yl)methanol
4a
was
chosen as a model compound for carrying out the oxidation reaction
(Scheme 4). The use of the Corey’s reagent (pyridinium chlor-
ochromate) in dichloromethane at room temperature in argon
atmosphere allows preparation of the target aldehyde in 12% yield
[11]. The PfitznereMoffatt oxidation (DMSO-DCC) [12] and oxidation
with MnO2 in CH2Cl2 at room temperature [13] lead to the formation
of aldehyde in similar yields (85 and 87%, respectively), the former
mode requiring an additional purification of the product. The puri-
fication was carried out either via the bisulphite derivative or by
means of column chromatography (SiO2, eluent e chloroform).
Other aldehydes, i.e. 1-aryl-5-ferrocenyl-1H-pyrazole-3-alde-
hydes, 5-ferrocenyl-1-methyl-1H-pyrazole-3-aldehyde and 5-fer-
rocenylisoxazole-3-aldehyde were obtained similarly. The overall
yields of the products from reduction and oxidation reactions were
82e94% (Scheme 5).
The 1H NMR spectra of compounds shows several sets of signals
assigned,respectively, totheprotonsofsubstitutedandunsubstituted
cyclopentadienyl rings (3.90e4.44 ppm), the CH-pyrazole proton
(6.54e7.13 ppm), and the protons of the ethyl and aryl substitutes. The
assignments of the signals in the 13C NMR spectra of ferrocenyl-
compounds were based on the HSQC spectra. In NOE-experiments,
the interaction between protons of the aryl substituent and those of
the substituted cyclopentadienyl ring revealed that counted in favor
the assigned structures of ethyl esters of 1-aryl-5-ferrocenyl-1H-
pyrazole-3-carboxylic acids. Moreover, for ethyl 1-(2-fluoro-3-chlor-
ophenyl)-5-ferrocenyl-3-pyrazolecarboxylate 3j, the molecular
structure was determined by means of X-ray analysis (Fig.1). It can be
mentioned that pyrazole and one of Cp moieties are almost coplanar
(the magnitude of the respective interplanar angle is 4.8ꢀ). At the
same time, the phenyl group is perpendicular to the plane of the
pyrazole moiety. The reason of these structural peculiarities is
the presence of Cl and F atoms which increase the steric hindrance in
3-ethylcarboxypyrazole fragment.
2.3. Reductive amination of 5a
The reactions of aldehydes or ketones with ammonia, primary
or secondary amines in the presence of reducing agents to give
primary, secondary, or tertiary amines, respectively, known as
reductive aminations (of the carbonyl compounds) or reductive
alkylations (of the amines) are among the most useful and impor-
tant tools in the synthesis of different kinds of amines. The
reductive amination reaction described as a direct reaction without
prior formation of the intermediate imine or iminium salt when
a carbonyl compound and an amine are mixed with the proper
reducing agent. The stepwise or indirect reaction involves the
formation of the intermediate imine followed by reduction in
a separate step.
The reaction of 2 with hydroxylamine hydrochloride leads to the
single product, ethyl ester 5-ferrocenyl-3-isoxazole carboxylic acid
3l (Scheme 5). At the same time, the condensation of 2 and methyl
hydrazine in boiling ethanol with catalytic amounts of acetic acid
yielded a mixture of two possible isomers with a ratio 60:40 (based
The obtainment of amino derivatives of 3-ferrocenyl-1-phenyl-4-
formylpyrazole that exhibited antimicrobial activity was reported in
a recently published paper [2]. These amino derivatives were
Scheme 1. Formation of ethyl 2,4-dioxo-4-ferrocenylbutanoate 2.

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A.N. Rodionov et al. / Journal of Organometallic Chemistry 696 (2011) 2108e2115
Scheme 2. Synthesis of esters of 5-ferrocenyl-1-aryl-1H-pyrazole-3-carboxylic acids.
prepared in overall yields of 80% by a two-step protocol. We have
prepared isomeric aminomethyl derivatives in the yields up to 92%
via a one-step procedure.
The primary and non-hindered secondary amines were used
successfully in these reactions (Scheme 6). However, the sterically
hindered diisopropylamine proved to yield another product, the
corresponding alcohol 4a.
and a representative cyclic voltammetric scan (CV) for 3l is
shown in Fig. 2.
All the compounds exhibit reversible one-electron waves. The
electrode potentials for all investigated compounds showed
a positive shift compared to that of ferrocene (0.46 V) indicative of
the electron withdrawing effect of the heterocyclic substituent, the
electron withdrawing effect of the isoxazole substituent being
greater than that of the pyrazole one. This is most likely connected
with the more electron-accepting effect of the isoxazole ring. The
introduction of electron-donating (CH3O-, 3d) or electron-with-
drawing groups (Cl-, F- 3j) to the phenyl ring of pyrazole derivatives
exerts no effect on the value of oxidation potentials. The electrode
potentials for all investigated species are comparable to those
previously reported for analogous compounds [4]. We can suggest
that this is a common property of all ferrocenyl-azole compounds
of such type.
2.4. Electrochemistry
It is well known that ferrocene is easily oxidized to the ferrici-
nium cation by one-electron oxidants [14]. The redox-potentials for
the ferroceneeferricinium couple range from 0.3 to 0.5 V. The
redox-potentials for ferrocene derivatives change within wider
limits. The potential depends on the electron-donating or electron
withdrawing abilities of the substituents. Thus, the redox proper-
ties can be rather strongly affected by altering the substituent
nature.
3. Experimental
The anodic electrochemistry of some compounds was investi-
gated by cyclic voltammetry in MeCN solution with [n-Bu4N][PF6]
as a supporting electrolyte. The results are summarized in Table 1
Melting points were determined with a Boethius microstage
and are uncorrected. 1H and 13C NMR spectra were recorded on
a Bruker DRX-300 and Bruker DRX-500 spectrometers at 300.13
(500.13) MHz and 75.5 (125.76) MHz for protons and 13C, respec-
tively, at 30 ꢀC in CDCl3 and DMSO. Chemical shifts are given in ppm
relative to solvent residual protons. The full assignments of all
reported NMR signals were made by the use of 1D and 2D NMR
experiments such as HSQC, HMBC, COSY, and NOESY correlation
techniques. IR spectra were recorded on a Carl Zeiss UR-20 spec-
trometer using a KBr disk. EI mass spectra were taken on a FIN-
NIGAN POLARIS Q spectrometer at 70 eV and the temperature of
the ion chamber 250ꢀS. The solvents were purified by standards
techniques. All reagents employed were purchased from Acros
Organics and used without purification.
3.1. Synthesis of ferrocenoylpyruvic acid ethyl ester (2)
To the suspension of 24.64 g (0.22 mol) of t-BuOK in benzene
(300 ml) was added acetylferrocene 45.6 g (0.2 mol). Diethyl
oxalate 27 ml (0.22 mol) was then added dropwise. The reaction
mixture was refluxed for 2 h and cooled to rt. The potassium salt
was filtered off, washed with ether, and suspended in CH2Cl2. The
CH2Cl2 suspension was treated with glacial acetic acid up to pH ¼ 5
and washed with water, saturated NaHCO3 and brine. The organics
were dried over Na2SO4, solvent was removed in vacuo. Deep
purple crystals, yield 89%, m.p. 77 ꢀC (m.p. 68e70 ꢀC [6]). 1H NMR
(500 MHz, CDCl3): 1.38 (t, J ¼ 7 Hz, 3H, CH3); 4.19 (s, 5H, Fc); 4.34 (q,
J ¼ 7 Hz, 2H, CH2); 4.62 (s, 2H, Fc); 4.85 (s, 2H, Fc); 6.54 (s, 1H, CH);
14.95 (br.s, 1H, OH). 13C NMR (126 MHz, CDCl3): 14.0, 62.2, 69.3,
Fig. 1. The molecular structure of 3j presented in thermal ellipsoids at 50% probability.
Principal bonds (Å and ꢀ): O(1)ꢁC(14) 1.339(3), O(1)eC(15) 1.452(3), O(2)eC(14) 1.200
(3), N(1)eN(2) 1.356(3), N(1)eC(11) 1.377(3), N(1)eC(17) 1.432(3), N(2)eC(13) 1.329
(3), Cl(1)eC(19) 1.728(3), F(1)eC(18) 1.341(3).

A.N. Rodionov et al. / Journal of Organometallic Chemistry 696 (2011) 2108e2115
2111
Scheme 3. Condensation of 2 with methyl hydrazine.
70.5, 73.4, 77.4, 100.0, 162.6, 163.6, 197.7. EIMS, m/z (RI%): 328 (Mþ,
62); 254 ([MeC2H4eCO2]þ, 100); 228 ([FcC(O)CH3]þ, 8); 213
([FcCO]þ, 17); 185 ([Fc]þ, 17).
3.2.3. Ethyl 5-ferrocenyl-1-p-tolyl-1H-pyrazole-3-carboxylate (3c)
Orange crystals, yield: 91%, m.p. 135e136 ꢀC. 1O NMR (500 MHz,
CDCl3): 1.44 (t, J ¼ 7 Hz, 3H, CH3); 2.42 (s, 3H, CH3); 4.07 (s, 5H, Fc);
4.14 (s, 2H, Fc); 4.20 (s, 2H, Fc); 4.46 (q, J ¼ 7 Hz, 2H, CH2); 7.02 (s,1H,
Pz); 7.24e7.26 (m, 4H, Ar).13C NMR(126 MHz, CDCl3): 14.4, 21.2, 61.0,
68.4, 68.9, 69.8, 73.5, 108.1, 126.4, 129.4, 137.4, 138.9, 143.7, 143.9,
126.2. Anal. Calcd. for C23H22FeN2P2: S, 66.68; O, 5.35; N, 6.76; Fe,
13.48. Found: S, 66.71; O, 5.38; N, 6.69; Fe,13.2. EI/MS, m/z (RI%): 414
(Mþ, 100); 386 ([MeC2H4]þ, 17); 342 ([MeC2H4eCO2]þ, 19); 277
([MeC2H4eCO2eCp]þ, 23).
3.2. General procedure 1. Synthesis of ethyl ferrocenylpyrazole-
carboxylate (3aek)
To a solution of ethyl ester of ferrocenoylpyruvic acid (2) (1.64 g,
5mmol)in20mlofethanolwasunderargonaddedthecorresponding
monosubstituted hydrazines hydrochlorides or hydroxylamine hyd-
rochloride (5.1 mmol). The resulting mixture was then heated while
refluxing for 4 h. Upon completion of the reaction, the mixture was
cooled to 0 ꢀC, the precipitate was isolated by filtration, washed with
cold ethanol (10 ml), recrystallized from ethanol and dried by Na2SO4.
3.2.4. Ethyl 5-ferrocenyl-1-(4-methoxyphenyl)-1H-pyrazole-3-
carboxylate (3d)
Deep orange crystals, yield: 86%, m.p. 170e171 ꢀC. 1O NMR
(500 MHz, CDCl3): 1.40 (t, J ¼ 7 Hz, 3H, CH3); 3.86 (s, 3H, CH3); 4.06
(s, 5H, Fc); 4.13 (s, 2H, Fc); 4.20 (s, 2H, Fc); 4.41 (q, J ¼ 7 Hz, 2H, CH2);
6.93 (d, J ¼ 8.3 Hz, 2H, Ar); 7.00 (s, 1H, Pz); 7.29 (d, J ¼ 8.3 Hz, 2H,
Ar). 13C NMR (126 MHz, CDCl3): 14.4, 55.5, 61.0, 68.4, 68.8, 69.8,
73.5, 107.8, 114.0, 128.0, 132.9, 143.8, 144.0, 159.9, 162.6. Anal. Calcd.
for C23H22FeN2P3: S, 64.20; O, 5.15; N, 6.51; Fe, 12.98. Found: S,
64.41; O, 5.14; N, 6.54; Fe,12.8. EI/MS, m/z (RI%): 430 (Mþ, 100); 402
([MeC2H4]þ, 13); 358 ([MeC2H4eCO2]þ, 13); 293 ([MeC2H4e
CO2eCp]þ, 11).
3.2.1. Ethyl 5-ferrocenyl-1-phenyl-1H-pyrazole-3-carboxylate (3a)
Orange crystals, yield 95%, m.p. 151e152 ꢀC. 1O NMR (500 MHz,
CDCl3): 1.43 (t, J ¼ 7.1 Hz, 3H, CH3); 4.06 (s, 5H, Fc); 4.13 (s, 2H, Fc);
4.19 (s, 2H, Fc); 4.45 (q, J ¼ 7.1 Hz, 2H, CH2); 7.03 (s,1H, Pz); 7.39e7.43
(m, 5H, Ph). 13C NMR (126 MHz, CDCl3): 14.4, 61.1, 68.6, 68.9, 69.8,
73.6, 108.4, 126.6, 128.8, 139.8, 143.8, 144.1, 162.3. EI/MS, m/z (RI%):
400 (Mþ,100); 372 ([MeC2H4]þ, 20); 328 ([MeC2H4eCO2]þ, 20);263
([MeC2H4eCO2eCp]þ, 23).
3.2.5. Ethyl 1-(4-tert-butylphenyl)-5-ferrocenyl-1H-pyrazole-3-
carboxylate (3e)
3.2.2. Ethyl 5-ferrocenyl-1-(naphthalen-1-yl)-1H-pyrazole-3-
carboxylate (3b)
Yellow crystals, yield: 92%, m.p. 124e125 ꢀC. 1O NMR (300 MHz,
CDCl3): 1.36 (s, 9H, CH3); 1.40 (t, J ¼ 7 Hz, 3H, CH3); 4.08 (s, 5H, Fc);
4.18 (s, 2H, Fc); 4.22 (s, 2H, Fc); 4.41 (q, J ¼ 7 Hz, 2H, CH2); 7.00 (s,
1H, Pz); 7.29 (d, J ¼ 8.1 Hz, 2H, Ar); 7.42 (d, J ¼ 8.1 Hz, 2H, Ar). 13C
NMR (75 MHz, CDCl3): 14.4, 31.24, 34.71, 60.9, 68.5, 68.9, 69.9, 73.7,
108.1, 125.7, 126.0, 137.3, 143.7, 143.9, 152.2, 162.6. Anal. Calcd. for
C26H28FeN2P2: S, 68.43; O, 6.18; N, 6.14; Fe, 12.24. Found: S, 68.18;
O, 6.10; N, 5.98; Fe, 11.6. EI/MS, m/z (RI%): 456 (Mþ, 100); 428
([MeC2H4]þ, 19); 384 ([MeC2H4eCO2]þ, 6); 263 ([MeC2H4e
CO2eCp]þ, 8).
Orange crystals, yield 89%, m.p. 200e201 ꢀC. 1O NMR (300 MHz,
CDCl3): 1.42 (t, J ¼ 6.5 Hz, 3H, CH3); 3.90 (br.s, 2H, Fc); 3.96 (s, 5H,
Fc); 4.05 (s, 2H, Fc); 4.44 (q, J ¼ 6.5 Hz, 2H, CH2); 7.13 (s,1H, Pz); 7.29
(d, J ¼ 7.5 Hz, 1H, Ar); 7.49e7.56 (m, 4H, Ar); 7.95 (d, J ¼ 7 Hz, 1H,
Ar); 8.04 (m, 1H, Ar). 13C NMR (75 MHz, CDCl3): 14.5, 61.1, 67.6, 69.0,
69.9, 72.6, 106.7, 122.9, 125.0, 125.9, 126.9, 127.5, 128.1, 130.3, 130.8,
134.0, 136.6, 144.6, 145.9, 162.7. Anal. Calcd. for C26H22FeN2P2: S,
69.35; O, 4.92; N, 6.22; Fe, 12.40. Found: S, 69.26; O, 4.91; N, 6.08;
Fe, 12.5. EI/MS, m/z (RI%): 450 (Mþ, 100); 422 ([MeC2H4]þ, 14); 378
([MeC2H4eCO2]þ, 10); 313 ([MeC2H4eCO2eCp]þ, 17).
Scheme 4. Synthesis of aldehydes 5a.

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Scheme 5. Synthesis of ferrocenylisoxazoles 3le5l.
3.2.6. Ethyl 5-ferrocenyl-1-(3-fluorophenyl)-1H-pyrazole-3-
carboxylate (3f)
4.25 (s, 2H, Fc); 4.45 (q, J ¼ 7 Hz, 2H, CH2); 7.04 (s, 1H, Pz); 7.23 (d,
J ¼ 7 Hz, 1H, Ar); 7.32e7.35 (m, 1H, Ar); 7.40 (d, J ¼ 7.5 Hz, 1H, Ar);
7.50 (c, 1H, Ar). 13C NMR (126 MHz, CDCl3): 14.4, 61.2, 68.8, 69.1,
69.9, 73.4, 109.0, 124.6, 126.7, 129.0, 129.7, 134.5, 140.7, 143.9, 144.5,
162.4. Anal. Calcd. for C22H19ClFeN2P2: S, 60.79; O, 4.41; N, 6.44;
Fe, 12.85. Found: S, 60.58; O, 4.39; N, 6.24; Fe, 12.6. EI/MS, m/z (RI
%): 434 (Mþ, 100); 406 ([MeC2H4]þ, 25); 362 ([MeC2H4eCO2]þ,
24); 297 ([MeC2H4eCO2eCp]þ, 22).
Deep orange crystals, yield: 85%, m.p. 143e144 ꢀC. 1O NMR
(500 MHz, CDCl3): 1.43 (t, J ¼ 7 Hz, 3H, CH3); 4.10 (s, 5H, Fc); 4.19 (s,
2H, Fc); 4.24 (s, 2H, Fc); 4.44 (q, J ¼ 7 Hz, 2H, CH2); 7.03 (s, 1H, Pz);
7.12e7.18 (m, 3H, Ar); 7.38 (m, 1H, Ar). 13C NMR (126 MHz, CDCl3):
14.4, 61.1, 68.8, 69.0, 69.9, 73.4, 109.0, 113.9 (d, J ¼ 24.4 Hz), 115.7 (d,
J ¼ 21.0 Hz), 122.1, 130.0 (d, J ¼ 8.8 Hz), 141.0 (d, J ¼ 10.1 Hz), 143.8,
144.4, 161.3 (d, J ¼ 249.1 Hz), 162.4. Anal. Calcd. for C22H19FFeN2P2:
S, 63.18; O, 4.58; N, 6.70; Fe, 13.35. Found: S, 63.28; O, 4.51; N,
6.69; Fe, 13.35. EI/MS, m/z (RI%): 418 (Mþ, 100); 390 ([MeC2H4]þ,
24); 346 ([MeC2H4eCO2]þ, 27); 281 ([MeC2H4eCO2eCp]þ, 27).
3.2.10. Ethyl 1-(3-chloro-2-fluorophenyl)-5-ferrocenyl-1H-
pyrazole-3-carboxylate (3j)
Yellow powder, yield: 84%, m.p. 177e178 ꢀC. 1O NMR (300 MHz,
CDCl3): 1.41 (t, J ¼ 7 Hz, 3H, CH3); 4.08 (s, 5H, Fc); 4.13 (s, 2H, Fc);
4.24 (s, 2H, Fc); 4.42 (q, J ¼ 7 Hz, 2H, CH2); 7.02 (s, 1H, Pz); 7.22 (m,
1H, Ar); 7.37 (m, 1H, Ar); 7.55 (m, 1H, Ar). 13C NMR (75 MHz, CDCl3):
14.4, 61.2, 67.5, 69.3, 69.9, 72.3, 107.4, 122.2 (J ¼ 16.3 Hz), 124.4
(J ¼ 5.3 Hz), 128.1, 129.2 (J ¼ 12.3 Hz), 132.0, 145.3, 145.7, 152.2
(J ¼ 254.1 Hz), 162.2. Anal. Calcd. for C22H19ClFFeN2P2: S, 58.37; O,
4.01; N, 6.19; Fe,12.34. Found: S, 58.41; O, 4.04; N, 6.25; Fe, 12.3. EI/
MS, m/z (RI%): 452 (Mþ, 100); 424 ([MeC2H4]þ, 21); 380
([MeC2H4eCO2]þ, 24); 315 ([MeC2H4eCO2eCp]þ, 27).
3.2.7. Ethyl 5-ferrocenyl-1-(4-fluorophenyl)-1H-pyrazole-3-
carboxylate (3g)
Yellow crystals, yield: 91%, m.p. 145 ꢀC. 1O NMR (500 MHz,
CDCl3): 1.39 (t, J ¼ 7.1 Hz, 3H, CH3); 4.06 (s, 5H, Fc); 4.10 (s, 2H, Fc);
4.20 (s, 2H, Fc); 4.41 (q, J ¼ 7.1 Hz, 2H, CH2); 7.00 (s, 1H, Pz); 7.08 (t,
J ¼ 8.4 Hz, 2H, Ar); 7.32e7.35 (m, 2H, Ar). 13C NMR (126 MHz,
CDCl3): 14.3, 61.0, 68.5, 68.9, 69.8, 73.2, 108.4, 115.6 (d, J ¼ 22.7 Hz),
128.2, 128.3, 135.7, 143.8 (d, J ¼ 27.7 Hz), 161.3 (d, J ¼ 249.5 Hz),
162.4. Anal. Calcd. for C22H19FFeN2P2: S, 63.18; O, 4.58; N, 6.70; Fe,
13.35. Found: S, 63.21; O, 4.67; N, 6.58; Fe, 13.3. EI/MS, m/z (RI%):
418 (Mþ, 100); 390 ([MeC2H4]þ, 26); 346 ([MeC2H4eCO2]þ, 28);
281 ([MeC2H4eCO2eCp]þ, 24).
3.2.11. Ethyl 5-ferrocenyl-1-methyl-1H-pyrazole-3-carboxylate
(3k)
Yellow crystals, yield: 75%, m.p. 139e140 ꢀC. 1O NMR (300 MHz,
CDCl3): 1.39 (t, J ¼ 7 Hz, 3H, CH3); 4.02 (s, 3H, CH3); 4.16 (s, 5H, Fc);
4.36 (s, 2H, Fc); 4.38 (q, J ¼ 7 Hz, 2H, CH2); 4.51 (s, 2H, Fc); 6.83 (s,1H,
Pz). 13C NMR (75 MHz, CDCl3): 14.3, 38.5, 60.8, 68.3, 69.2, 69.6, 73.8,
108.2, 142.3, 142.8, 162.4. Anal. Calcd. for C17H18FeN2P2,0.5H2O: S,
58.81; O, 5.52; N, 8.07; Fe,16.08. Found:S, 59.06; O, 5.55; N, 7.92; Fe,
16.9. EI/MS, m/z (RI%): 338 (Mþ, 100); 310 ([MeC2H4]þ, 28); 265
([MeC2H4eCO2]þ, 27); 201 ([MeC2H4eCO2eCp]þ, 22).
3.2.8. Ethyl 1-(2-chlorophenyl)-5-ferrocenyl-1H-pyrazole-3-
carboxylate (3h)
Yellow powder, yield: 84%, m.p. 146 ꢀC. 1O NMR (500 MHz,
CDCl3): 1.44 (t, J ¼ 7 Hz, 3H, CH3); 4.11 (s, 5H, Fc); 4.14 (br.s, 2H, Fc);
4.22 (s, 2H, Fc); 4.45 (q, J ¼ 7 Hz, 2H, CH2); 7.02 (s, 1H, Pz); 7.42e7.51
(m, 3H, Ar); 7.57 (d, J ¼ 7.5 Hz, 1H, Ar). 13C NMR (126 MHz, CDCl3):
14.4, 61.1, 67.7, 69.4, 70.2, 72.8, 106.9, 127.5, 130.0, 130.3, 131.1, 133.1,
137.9, 144.8, 145.4, 162.5. Anal. Calcd. for C22H19ClFeN2P2: S, 60.79;
O, 4.41; N, 6.44; Fe,12.85. Found: S, 60.64; O, 4.44; N, 6.29; Fe,12.9.
EI/MS, m/z (RI%): 434 (Mþ, 100); 406 ([MeC2H4]þ, 12); 362
([MeC2H4eCO2]þ, 5); 297 ([MeC2H4eCO2eCp]þ, 17).
3.2.12. Ethyl 5-ferrocenylisoxazole-3-carboxylate (3l)
Deep orange crystals, yield: 86%, m.p. 92e93 ꢀC. 1O NMR
(500 MHz, CDCl3): 1.43 (t, J ¼ 7.2 Hz, 3H, CH3); 4.14 (s, 5H, Fc); 4.44
(s, 2H, Fc); 4.46 (q, J ¼ 7.2 Hz, 2H, CH2); 4.77 (s, 2H, Fc); 6.54 (s, 1H,
Az). 13C NMR (126 MHz, CDCl3): 14.1, 62.1, 67.2, 69.9, 70.0, 70.4, 98.4,
156.7, 160.2, 173.8. Anal. Calcd. for C17H18FeN2P2,H2O: S, 56.00; O,
4.99; N, 4.08. Found: S, 55.69; O, 4.99; N, 4.09. EI/MS, m/z (RI%):
325 (Mþ, 100); 297 ([MeC2H4]þ, 10); 253 ([MeC2H4eCO2]þ, 44);
188 ([MeC2H4eCO2eCp]þ, 22).
3.2.9. Ethyl 1-(3-chlorophenyl)-5-ferrocenyl-1H-pyrazole-3-
carboxylate (3i)
Orange crystals, yield: 86%, m.p. 121e122 ꢀC. 1O NMR (500 MHz,
CDCl3): 1.44 (t, J ¼ 7 Hz, 3H, CH3); 4.12 (s, 5H, Fc); 4.18 (s, 2H, Fc);
Scheme 6. Reductive amination of 5a.

A.N. Rodionov et al. / Journal of Organometallic Chemistry 696 (2011) 2108e2115
2113
104.7, 126.0, 129.3, 137.7, 138.1, 142.8, 152.6. EI/MS, m/z (RI%): 372 (Mþ,
100); 370 ([Me2H]þ, 27); 352 ([MeCH2O]þ, 5); 307 ([MeCp]þ, 8).
Table 1
Electrochemical data of some compounds.
ꢀ
N
Oxidation F1/2, V
D
F1/2, V
Reduction Fr, V
3.3.4. (5-Ferrocenyl-1-(4-methoxyphenyl)-1H-pyrazol-3-yl)
methanol (4d)
3a
3d
3j
3l
4a
4l
0.69
0.54
0.57
0.64
0.51
0.59
0.54
0.46
0.23
0.08
0.11
0.18
0.05
0.13
0.08
Orange powder, yield: 96%, m.p. 150e151. 1O NMR (500 MHz,
CDCl3): 3.44 (br.s, 1H, OH); 3.83 (s, 3H, CH3); 4.05 (s, 5H, Fc); 4.12 (s,
2H, Fc); 4.17 (s, 2H, Fc); 4.71 (s, 2H, CH2); 6.49 (s, 1H, Pz); 6.91 (d,
J ¼ 8.8 Hz, 2H, Ar); 7.25 (d, J ¼ 8.8 Hz, 2H, Ar). 13C NMR (126 MHz,
CDCl3): 55.4, 58.6, 68.3, 68.5, 69.6, 74.4, 104.2, 113.8, 127.6, 133.2,
142.9, 152.4, 159.3. EI/MS, m/z (RI%): 386 (Mþ, 100); 384 ([Me2H]þ,
12); 356 ([MeCH2O]þ, 4); 321 ([MeCp]þ, 12).
ꢁ1.97
ꢁ2.05
5a
FcH
3.3. General procedure 2. Synthesis of alcohols 4ael
3.3.5. (1-(4-tert-Butylphenyl)-5-ferrocenyl-1H-pyrazol-3-yl)
methanol (4e)
Ethyl 5-ferrocenyl-3-carboxylates 3ael (5 mmol) dissolved in
anhydrous THF (50 ml) were slowly added to a stirred solution of
lithium aluminum hydride (0.2 g, 5 mmol) in the 1,4-dioxane
(50 ml). The mixture was refluxed for 1 h, stirred overnight at room
temperature, cooled with an ice bath and treated by brine (0.5 ml).
The resulting mixture was filtered, the inorganic precipitate was
washed three times with diethyl ether, the solution was dried
(sodium sulfate), and the solvent evaporated under reduced pres-
sure to give the fine products.
Dark orange oil, yield: 85%.1O NMR (500 MHz, CDCl3): 1.37 (s, 9H,
CH3); 2.04 (br.s, 1H, OH); 4.08 (s, 5H, Fc); 4.17 (s, 2H, Fc); 4.20 (s, 2H,
Fc); 4.75 (s, 2H, CH2); 6.52 (s,1H, Pz); 7.26 (d, J ¼ 8.3 Hz, 2H, Ar); 7.42
(d, J ¼ 8.3 Hz, 2H, Ar). 13C NMR (126 MHz, CDCl3): 31.3, 34.7, 58.8,
68.5, 68.6, 69.7, 74.6, 104.7, 125.6, 125.7, 137.5, 142.8, 151.4, 152.5. EI/
MS, m/z (RI%): 414 (Mþ,100); 412 ([Me2H]þ,10); 349 ([MeCp]þ,14).
3.3.6. (5-Ferrocenyl-1-(3-fluorphenyl)-1H-pyrazol-3-yl)methanol
(4f)
Dark orange oil, yield: 90%. 1O NMR (300 MHz, CDCl3): 2.83 (br.s,
1H, OH); 4.10 (s, 5H, Fc); 4.18 (s, 2H, Fc); 4.22 (s, 2H, Fc); 4.74 (s, 2H,
CH2); 6.55 (s, 1H, Pz); 7.03e7.11 (m, 3H, Ar); 7.29e7.39 (m, 1H, Ar).
13C NMR (75 MHz, CDCl3): 58.8, 68.7, 68.9, 69.8, 74.6, 105.8, 113.1 (d,
J ¼ 14.5 Hz), 114.6 (d, J ¼ 12.5 Hz), 122.4, 129.7 (d, J ¼ 5.3 Hz), 141.3
(d, J ¼ 5.7 Hz), 142.8, 153.1, 161.3 (d, J ¼ 147.7 Hz). EI/MS, m/z (RI%):
376 (Mþ, 100); 311 ([MeCp]þ, 8).
3.3.1. (5-Ferrocenyl-1-phenyl-1H-pyrazol-3-yl)methanol (4a)
Yellow powder, yield: 95%, m.p. 105e106. 1O NMR (500 MHz,
CDCl3): 2.67 (br.s, 1H, OH); 4.07 (s, 5H, Fc); 4.14 (s, 2H, Fc); 4.18 (s,
2H, Fc); 4.75 (s, 2H, CH2); 6.53 (s, 1H, Pz); 7.33e7.42 (m, 5H, Ar). 13
C
NMR (126 MHz, CDCl3): 52.7, 67.8, 68.5, 69.2, 78.3, 118.4, 125.7,
125.7, 127.6, 129.3, 140.1, 150.7, 155.2. Anal. Calcd. for
C20H18FeN2P,1/3H2O: S, 65.95; O, 5.17; N, 7.69. Found: S, 65.94; O,
5.04; N, 7.26. EI/MS, m/z (RI%): 358 (Mþ, 100); 356 ([Me2H]þ, 16);
293 ([MeCp]þ, 7).
3.3.7. (5-Ferrocenyl-1-(4-fluorphenyl)-1H-pyrazol-3-yl)methanol
(4g)
Dark orange oil, yield: 95%. 1O NMR (300 MHz, CDCl3): 2.56 (br.s,
1H, OH); 4.09 (s, 5H, Fc); 4.18 (s, 2H, Fc); 4.20 (s, 2H, Fc); 4.70 (s, 2H,
CH2); 6.54 (s, 1H, Pz); 7.08e7.12 (m, 2H, Ar); 7.32e7.39 (m, 2H, Ar).
EI/MS, m/z (RI%): 376 (Mþ, 100); 311 ([MeCp]þ, 10).
3.3.2. (5-Ferrocenyl-1-(naphthalen-1-yl)-1H-pyrazol-3-yl)
methanol (4b)
Orange oil, yield: 89%. 1O NMR (500 MHz, CDCl3): 1.92 (br.s, 1H,
OH); 4.16 (s, 5H, Fc); 4.39 (s, 2H, Fc); 4.90 (s, 2H,); 4.93 (s, 2H, Fc);
7.48e7.57 (m, 2H, Ar); 7.87e7.96 (m, 4H, Ar); 8.04 (s,1H, Ar); 8.13 (s,
1H, Ar). 13C NMR (126 MHz, CDCl3): 56.2, 67.4, 68.9, 69.4, 77.6, 115.6,
118.2, 120.7, 125.7, 126.9, 127.3, 127.8, 127.9, 129.4, 131.7, 133.7, 137.4,
150.3. EI/MS, m/z (RI%): 408 (Mþ, 100); 406 ([Me2H]þ, 14); 343
([MeCp]þ, 9).
3.3.8. (1-(2-Chlorophenyl)-5-ferrocenyl-1H-pyrazol-3-yl)methanol
(4h)
Orange oil, yield: 94%. 1O NMR (500 MHz, CDCl3): 3.32 (br.s, 1H,
OH); 4.02 (s, 5H, Fc); 4.03 (s, 2H, Fc); 4.11 (s, 2H, Fc); 4.64 (s, 2H,
CH2); 6.52 (s, 1H, Pz); 7.29e7.41 (m, 3H, Ar); 7.49 (d, J ¼ 7.5 Hz, Ar).
13C NMR (75 MHz, CDCl3): 58.5, 67.4, 68.8, 69.8, 73.4, 103.3, 127.5,
130.1, 130.2, 130.7, 133.0, 138.1, 144.5, 153.6. EI/MS, m/z (RI%): 392
(Mþ, 100); 390 ([Me2H]þ, 20); 327 ([MeCp]þ, 8).
3.3.3. (5-Ferrocenyl-1-(p-tolyl)-1H-pyrazol-3-yl)methanol (4c)
Orange oil, yield: 93%.1O NMR(500 MHz, CDCl3): 2.39(s, 3H, CH3);
3.39 (br.s,1H, OH); 4.05 (s, 5H, Fc); 4.13 (s, 2H, Fc); 4.16 (s, 2H, Fc); 4.71
(s, 2H, CH2); 6.50 (s, 1H, Pz); 7.18 (d, J ¼ 8.5 Hz, 2H, Ar); 7.30 (d,
J¼8.4Hz,2H, Ar).13CNMR(126MHz, CDCl3):21.1, 58.7,68.5, 69.7, 74.6,
3.3.9. (1-(3-Chlorophenyl)-5-ferrocenyl-1H-pyrazol-3-yl)methanol
(4i)
Orange oil, yield: 90%. 1O NMR (500 MHz, CDCl3): 3.20 (br.s, 1H,
OH); 4.10 (s, 5H, Fc); 4.16 (s, 2H, Fc); 4.22 (s, 2H, Fc); 4.73 (s, 2H,
CH2); 6.50 (s, 1H, Pz); 7.16 (d, J ¼ 7.5 Hz, Ar); 7.26e7.30 (m, 1H, Ar);
7.32 (d, J ¼ 8.5 Hz, Ar); 7.42 (s, 1H, Ar). 13C NMR (126 MHz, CDCl3):
58.6, 68.6, 68.8, 69.8, 74.5, 105.8, 124.0, 126.0, 127.9, 129.6, 134.3,
141.0, 142.9, 153.3. EI/MS, m/z (RI%): 392 (Mþ, 100); 390 ([Me2H]þ,
22); 327 ([MeCp]þ, 5).
3.3.10. (1-Methyl-5-ferrocenyl-1H-pyrazol-3-yl)methanol (4k)
Orange powder, yield: 96%, m.p. 106e107. 1O NMR (300 MHz,
CDCl3): 2.54 (br.s, 1H, OH); 3.92 (s, 3H, CH3); 4.16 (s, 5H, Fc); 4.33 (t,
2H, J ¼ 1.8 Hz, Fc); 4.47 (t, 2H, J ¼ 1.8 Hz, Fc); 4.67 (s, 2H, CH2); 6.30
(s, 1H, Pz). 13C NMR (75 MHz, CDCl3): 26.8, 58.3, 68.2, 68.8, 69.4,
74.4, 104.2, 142.0, 151.0, 159.3. EI/MS, m/z (RI%): 296 (Mþ, 100); 384
([Me2H]þ, 13); 231 ([MeCp]þ, 4).
Fig. 2. Cyclic voltammogram for ferrocenylisoxazole 3l in MeCN.

2114
A.N. Rodionov et al. / Journal of Organometallic Chemistry 696 (2011) 2108e2115
3.3.11. (5-Ferrocenylisoxazol-3-yl)methanol (4l)
3.4.6. 5-Ferrocenyl-1-(3-fluorphenyl)-1H-pyrazole-3-carbaldehyde
(5f)
Dark orange powder, yield: 90%, m.p. 103e104 ꢀC. 1O NMR
(500 MHz, CDCl3): 2.28 (br.s, 1H, OH); 4.15 (s, 5H, Fc); 4.42 (s, 2H,
Fc); 4.74 (s, 2H, CH2); 4.79 (s, 2H, Fc); 6.22 (s, 1H, CH). 13C NMR
(126 MHz, CDCl3): 57.1, 67.0, 68.5, 69.8, 70.8, 96.7, 163.7, 172.1. Anal.
Calcd. for C14H13FeNP2: S, 59.40; O, 4.63; N, 4.95; Fe, 19.73. Found:
S, 59.22; O, 4.61; N, 4.65; Fe, 19.7.
Orange powder, yield: 84%, m.p. 118e120 ꢀC. IR: 1705 cmꢁ1 (CO).
1O NMR (500 MHz, CDCl3): 4.12 (s, 5H, Fc); 4.20 (s, 2H, Fc); 4.27 (s,
2H, Fc); 7.03 (s, 1H, Pz); 7.16e7.17 (m, 3H, Ar); 7.40e7.41 (m, 1H, Ar);
10.04 (s, 1H, CHO). 13C NMR (126 MHz, CDCl3): 69.0, 69.2, 69.9, 73.3,
105.9, 113.4 (d, J ¼ 25.5 Hz), 115.8 (d, J ¼ 21 Hz), 130.2 (d, J ¼ 9 Hz),
140.7 (d, J ¼ 10.5 Hz), 144.6, 151.7, 161.5 (d, J ¼ 247.5 Hz), 186.8. EI/
MS, m/z (RI%): 374 (Mþ, 100); 309 ([MeCp]þ, 5).
3.4. General procedure 3. Synthesis of aldehydes 5ael
To avigorously stirred suspension of manganese (IV) oxide (0.87 g,
10 mmol) in dry methylene chloride (10 ml) was dropwise added
a solution of the appropriate alcohols 4ael (2 mmol) in methylene
chloride (10 ml). The resulting slurry was stirred at room temperature
for3 h. Addition ofdiethyl ether (20ml)followedby filtration through
a Celite pad and concentration invacuoaffordedazolealdehydes5ael.
3.4.7. 5-Ferrocenyl-1-(4-fluorphenyl)-1H-pyrazole-3-carbaldehyde
(5g)
Orange powder, yield: 82%, m.p.124e125 ꢀC. IR: 1704 cmꢁ1 (CO).
1O NMR (500 MHz, CDCl3): 4.09 (s, 5H, Fc); 4.15 (s, 2H, Fc); 4.25 (s,
2H, Fc); 7.01 (s, 1H, Pz); 7.13 (t, J ¼ 8.5 Hz, 2H, Ar); 7.35e7.40 (m, 2H,
Ar); 10.02 (s, 1H, CHO). 13C NMR (126 MHz, CDCl3): 68.8, 69.0, 69.8,
73.2, 105.3, 115.9 (d, J ¼ 23.9 Hz), 127.8 (d, J ¼ 8.8 Hz), 135.7, 144.7,
151.5, 161.5 (d, J ¼ 250.7 Hz), 186.8. Anal. Calcd. for C20H15FFeN2P:
S, 64.20; O, 4.04; N, 7.49; Fe, 14.92. Found: S, 64.14; O, 4.05; N,
7.61; Fe, 15.0. EI/MS, m/z (RI%): 374 (Mþ, 100); 309 ([MeCp]þ, 6).
3.4.1. 5-Ferrocenyl-1-phenyl-1H-pyrazole-3-carbaldehyde (5a)
Orange powder, yield: 86%, m.p. 142 ꢀC. IR: 1700 cmꢁ1 (CO). 1O
NMR(300MHz,CDCl3):4.09(s, 5H, Fc);4.16(s, 2H,Fc);4.23(s, 2H, Fc);
7.03 (s,1H, Pz); 7.37e7.41 (m, 2H, Ar); 7.47e7.49 (m, 3H, Ar); 10.04 (s,
1H, CHO). 13C NMR (126 MHz, CDCl3): 68.9, 69.1, 70.0, 73.5, 105.2,
126.0,129.0,139.6,144.6,151.5,187.0. Anal. Calcd. for C20H16FeN2P: S,
67.44; O, 4.53; N, 7.86; Fe,15.68. Found: S, 67.52; O, 4.60; N, 7.76; Fe,
15.17. EI/MS, m/z (RI%): 356 (Mþ, 100); 391 ([MeCp]þ, 9).
3.4.8. 5-Ferrocenyl-1-methyl-1H-pyrazole-3-carbaldehydꢁe1(5k)
Orange powder, yield: 94%, m.p. 98 ꢀC. IR: 1694 cm (CO). 1O
NMR (300 MHz, CDCl3): 4.03 (s, 3H, CH3); 4.22 (s, 5H, Fc); 4.43 (s,
2H, Fc); 4.56 (s, 2H, Fc); 6.79 (s,1H, Pz); 9.93 (s,1H, CHO). EI/MS, m/z
(RI%): 294 (Mþ, 100).
3.4.2. 5-Ferrocenyl-1-(naphthalen-1-yl)-1H-pyrazole-3-
carbaldehyde (5b)
3.4.9. 5-Ferrocenylisoxazole-3-carbaldehyde (5l)
Deep orange powder, yield: 87%, m.p. 187e189 ꢀC. IR: 1713 cmꢁ1
(CO). 1O NMR (300 MHz, CDCl3): 3.84 (br.s, 2H, Fc); 3.96 (s, 5H, Fc);
4.08 (s, 2H, Fc); 7.11 (s, 1H, Pz); 7.37e7.41 (m, 2H, Ar); 7.47e7.49 (m,
3H, Ar); 10.04 (s, 1H, CHO). 13C NMR (76 MHz, CDCl3): 67.7, 69.2,
69.8, 72.1, 103.1, 122.5, 125.0, 125.6, 127.1, 127.8, 128.3, 130.4, 130.5,
134.1, 136.2, 146.8, 151.9, 187.1. Anal. Calcd. for C24H18FeN2P: S,
70.95; O, 4.47; N, 6.90; Fe, 13.75. Found: S, 70.59; O, 4.41; N, 6.71;
Fe, 14.0. EI/MS, m/z (RI%): 406 (Mþ, 100); 341 ([MeCp]þ, 24).
Orange powder, yield: 87%, m.p.140e141 ꢀC. IR: 1691 cmꢁ1 (CO).
1O NMR (500 MHz, CDCl3): 4.15 (s, 5H, Fc); 4.67 (s, 2H, Fc); 4.79 (s,
2H, Fc); 6.51 (s, 1H, Az); 10.16 (s, 1H, CHO). 13C NMR (150 MHz,
CDCl3): 67.3, 69.6, 70.0, 70.5, 94.7, 162.5, 174.3, 185.0. Anal. Calcd. for
C14H11FeNP2: S, 59.82; O, 3.94; N, 4.98. Found: S, 59.74; O, 3.91; N,
4.95. EI/MS, m/z (RI%): 281 (Mþ, 100); 253 ([MeCO]þ, 54); 309
([MeCOeCp]þ, 42).
3.5. General procedure for reductive amination
3.4.3. 5-Ferrocenyl-1-(p-tolyl)-1H-pyrazole-3-carbaldehyde (5c)
Orange powder, yield: 90%, m.p. 140e141 ꢀC. IR: 1710 cmꢁ1 (CO).
1O NMR (300 MHz, CDCl3): 2.44 (s, 3H, CH3); 4.08 (s, 5H, Fc); 4.16 (t,
J ¼ 1.7 Hz, 2H, Fc); 4.22 (t, J ¼ 1.7 Hz, 2H, Fc); 7.01 (s, 1H, Pz); 7.27
(m, 4H, Ar); 10.03 (s, 1H, CHO). 13C NMR (76 MHz, CDCl3): 21.2, 68.7,
69.0, 69.9, 73.3, 104.9, 125.8, 129.6, 137.1, 139.2, 144.6, 151.3, 187.1.
Anal. Calcd. for C21H18FeN2P: S, 68.13; O, 4.90; N, 7.57; Fe, 15.2.
Found: S, 68.19; O, 4.91; N, 7.44; Fe, 15.08. EI/MS, m/z (RI%): 370
(Mþ, 100); 305 ([MeCp]þ, 12).
Ferrocenylformylpyrazole 5a (1 mmol 0.356 g) and the corre-
sponding amine (1.2 mmol) were mixed in 1,2-dichloroethane
(35 ml) for 1 h at rt and treated with sodium triacetoxyborohydride
(0.3 g, 1.4 mmol). The mixture was refluxed for 1 h. The reaction
mixture was quenched by adding aqueous saturated NaHCO3, and
the product was extracted with dichloromethane (2 ꢂ 30 ml). The
organic layers were combined, washed with small amounts of
brine, and dried over Na2SO4. The solvent was evaporated and the
residue purified by means of column chromatography (SiO2, eluent
CHCl3eMeOH 9/1).
3.4.4. 5-Ferrocenyl-1-(4-methoxyphenyl)-1H-pyrazole-3-
carbaldehyde (5d)
Orange powder, yield: 87%, m.p. 174 ꢀC. IR: 1703 cmꢁ1 (CO). 1O
NMR (300 MHz, CDCl3): 3.87 (s, 3H, CH3); 4.07 (s, 5H, Fc); 4.15 (s, 2H,
Fc); 4.22 (s, 2H, Fc); 6.96 (d, J ¼ 8.6 Hz, 2H, Ar); 6.99 (s,1H, Pz); 7.30 (d,
J ¼ 8.6 Hz, 2H, Ar); 10.02 (s,1H, CHO).13C NMR (76 MHz, CDCl3): 55.5,
68.6, 69.0, 69.8, 73.2, 104.6, 114.1, 127.4, 132.6, 144.7, 151.2, 159.9,
187.1. EI/MS, m/z (RI%): 386 (Mþ, 100); 321 ([MeCp]þ, 11).
3.5.1. 3-(t-Butylaminomethyl)-5-ferrocenyl-1- phenyl-1H-pyrazole
(6a)
Orange powder, yield: 72%, m.p. 200e202 ꢀC. 1O NMR
(500 MHz, CDCl3): 1.43 (s, 9H, CH3); 4.06 (s, 5H, Fc); 4.10 (s, 2H, Fc);
4.12 (s, 2H, Fc); 4.14 (s, 2H, CH2); 7.01 (s, 1H, Pz); 7.30e7.42 (m, 5H,
Ar). 13C NMR (126 MHz, CDCl3): 12.8, 26.8, 39.6, 68.4, 68.6, 69.6,
74.0, 107.2, 126.0, 128.1, 128.6, 139.8, 143.2, 146.1. Anal. Calcd. for
C24H27FeN3P: C, 69.74; H, 6.58; N,10.17. Found: S, 69.89; O, 6.51; N,
10.08. EI/MS, m/z (RI%): 413 (Mþ, 28); 341 ([Me((CH3)3NH2)]þ, 100).
3.4.5. 1-(4-tert-Butylphenyl)-5-ferrocenyl-1H-pyrazole-3-
carbaldehyde (5e)
Orange powder, yield: 92%, m.p.169e170 ꢀC. IR: 1700 cmꢁ1 (CO).
1O NMR (300 MHz, CDCl3): 1.38 (s, 9H, CH3); 4.09 (s, 5H, Fc); 4.19 (t,
J ¼ 1.9 Hz, 2H, Fc); 4.24 (t, J ¼ 1.9 Hz, 2H, Fc); 7.01 (s, 1H, Pz);
7.29e7.34 (m, 2H, Ar); 7.46e7.50 (d, J ¼ 8.6 Hz, 2H, Ar); 10.03 (s, 1H,
CHO). 13C NMR (76 MHz, CDCl3): 31.3, 34.8, 68.8, 69.0, 69.9, 73.3,
104.9, 125.5, 126.0, 137.0, 144.6, 151.3, 152.4, 187.2. EI/MS, m/z (RI%):
412 (Mþ, 100); 347 ([MeCp]þ, 8).
3.5.2. 3-(n-Butylaminomethyl)-5-ferrocenyl-1-phenyl-1H-pyrazole
(6b)
Orange oil, yield: 81%. 1O NMR (500 MHz, CDCl3): 0.87 (t, 3H,
CH3); 1.23e1.28 (m, 2H, CH2); 1.30e1.35 (m, 2H, CH2); 1.48e1.53
(m, 2H, CH2); 3.28 (s, 2H, CH2); 4.08 (s, 5H, Fc); 4.17 (s, 2H, Fc); 4.25
(s, 2H, Fc); 6.66 (s, 1H, Pz); 7.32e7.35 (m, 2H, Ar); 7.46e7.50 (m, 3H,

A.N. Rodionov et al. / Journal of Organometallic Chemistry 696 (2011) 2108e2115
2115
Ar). 13C NMR (126 MHz, CDCl3): 13.7, 19.8, 30.6, 47.0, 48.8, 68.1, 68.5,
3.6. Electrochemistry
69.5, 74.3, 106.8, 126.0, 128.1, 128.8, 140.0, 143.5, 146.2. EI/MS, m/z
(RI%): 413 (Mþ, 30); 342 ([Me(C3H7CH]NH)]þ, 100).
The electrochemical (cyclic voltammetry) measurements were
performed on a IPC-Pro potentiostat. The working electrode was
a glassy carbon disk (s ¼ 2 mm), the auxiliary electrode was
a platinum plate. All the potential values were referred to the
Saturated Calomel Electrode (SCE). The experiments were carried
out at c ¼ 2$10ꢁ3 M under argon in deoxygenated acetonitrile
solution containing 0.1 M [(n-Bu)4N]PF6, as a supporting electro-
3.5.3. 5-Ferrocenyl-1-phenyl-3-(pyrrolidin-1-ylmethyl)-1H-
pyrazole (6c)
Orange oil, yield: 87%. 1O NMR (500 MHz, CDCl3): 1.90 (m, 4H,
CH2); 2.96 (m, 4H, CH2); 3.95 (s, 2H, CH2); 4.04 (s, 5H, Fc); 4.10 (s,
2H, Fc); 4.14 (s, 2H, Fc); 6.70 (s, 1H, Pz); 7.28e7.35 (m, 5H, Ar). 13C
NMR (126 MHz, CDCl3): 23.3, 51.9, 53.0, 68.4, 68.5, 69.7, 74.3, 107.2,
125.8, 127.9, 128.6, 139.9, 142.8, 147.0. EI/MS, m/z (RI%): 413 (Mþ,
35); 341 ([MeC4H9N]þ, 100).
lyte. The scan rate was 0.2 Vsꢁ1
.
3.7. X-ray analysis of compound 3j
3.5.4. 5-Ferrocenyl-1-phenyl-3-(piperidine-1-ylmethyl)-1H-
pyrazole (6d)
Crystallographic data for 3j: crystals of C22H18ClFFeN2O2 are
monoclinic, space group C2/c, a ¼ 13.500 (3) Å, b ¼ 16.398 (4) Å,
Orange powder, yield: 89%, m.p. 178 ꢀC. 1O NMR (500 MHz,
CDCl3): 1.49 (m, 2H, CH2); 1.71e1.76 (m, 4H); 2.68 (m, 4H); 3.78 (s,
2H, CH2); 4.04 (s, 5H, Fc); 4.14 (s, 2H, Fc); 4.15 (s, 2H, Fc); 6.67 (s, 1H,
Pz); 7.31e7.39 (m, 5H, Ar). 13C NMR (126 MHz, CDCl3): 23.5, 24.8,
53.8, 55.7, 68.4, 68.6, 69.6, 74.5, 107.3, 125.9, 127.8, 128.6, 140.0,
142.6, 147.5. Anal. Calcd. for C25H27FeN3P: C, 70.59; H, 6.40; N, 9.88.
Found: S, 70.29; O, 6.31; N, 9.86. EI/MS, m/z (RI%): 424 ([MeH]þ,
100); 342 ([MeC5H9N]þ, 46).
c ¼ 17.622 (4) Å,
b
¼ 99.028 (5)ꢀ, V ¼ 3852.5 (16) Å3, Z ¼ 8, M ¼ 452.68,
dcalc ¼ 1.278 g cmꢁ3
,
m
(MoK
a
) ¼ 0.95 mmꢁ1, F(000) ¼ 1856. Inten-
sities of 21982 reflections were measured with a Bruker Smart 1000
diffractometer at 100K [l(MoKa) ¼ 0.71073 Å], and 5589 indepen-
dent reflections (Rint ¼ 0.0574) were used in the further refinement.
The structure was solved by direct method. All non-hydrogen atoms
were refined in anisotropic approximation against F2. Hydrogen
atoms were refined in the rigid body approximation with the Uiso(H)
parameters equal to 1.2 Ueq(C) and 1.5 Ueq(C) for methyl group, where
Ueq(C,) respectively are the equivalent thermal parameters of the
carbon and nitrogen atoms to which the corresponding H atoms are
bonded. The refinement converged to wR2 ¼ 0.0775 and GOF ¼ 1.020
for all independent reflections [R1 ¼ 0.0477 was calculated against
3.5.5. 5-Ferrocenyl-1-phenyl-3-(morpholine-1-ylmethyl)-1H-
pyrazole (6e)
Orange powder, yield: 91%, m.p. 116e118 ꢀC. 1O NMR (500 MHz,
CDCl3): 2.59 (m, 4H); 3.63 (s, 2H, CH2); 3.77e3.79 (m, 4H); 4.04 (s,
5H, Fc); 4.13 (s, 2H, Fc); 4.16 (s, 2H, Fc); 6.50 (s,1H, Pz); 7.33e7.41 (m,
5H, Ar). 13C NMR (126 MHz, CDCl3): 55.4, 56.2, 66.8, 68.3, 68.5, 69.7,
74.7, 106.5, 125.9, 127.7, 128.5, 140.1, 142.3, 149.1. Anal. Calcd. for
C24H25FeN3P: S, 67.46; O, 5.90; N, 9.83. Found: S, 67.02; O, 5.84; N,
9.43. EI/MS, m/z (RI%): 427 ([M]þ, 44); 342 ([MeC4H7NO]þ, 100).
F for 3356 observed reflections with I > 2s(I)].
Acknowledgments
This work was partially supported by the Russian Academy of
Sciences (Presidium Programs «Support for Young Scientists» and
«Fundamental Sciences e for Medicine»), the Department of
Chemistry and Materials Science (Project 10), and the Russian
3.5.6. 5-Ferrocenyl-1-phenyl-3-(4-methylpiperidine-1-ylmethyl)-
1H-pyrazole (6f)
Orange powder, yield: 89%, m.p. 109e111 ꢀC. 1O NMR (500 MHz,
CDCl3): 0.96 (d, J ¼ 6.3, 3H, CH3); 1.50 (m, 1H, CH); 1.61e1.75 (m,
4H); 2.48e2.44 (m, 2H); 3.22e3.25 (m, 2H); 3.92 (s, 2H, CH2); 4.06
(s, 5H, Fc); 4.14 (s, 2H, Fc); 4.17 (s, 2H, Fc); 6.80 (s, 1H, Pz); 7.29e7.40
(m, 5H, Ar). 13C NMR (126 MHz, CDCl3): 21.1, 29.5, 32.1, 52.7, 54.6,
68.5, 68.7, 69.8, 74.1, 107.8, 125.9, 128.0, 128.7, 139.9, 143.1, 145.8. EI/
MS, m/z (RI%): 439 ([M]þ, 18); 342 ([MeC6H11N]þ, 100).
ꢀ
Foundation for Basic Research (RFBR N 09-03-00535).
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CH2); 3.78 (s, 3H, CH3); 3.93 (br.s, 2H, CH2); 4.06 (s, 5H, Fc); 4.13 (s,
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