Synthesis of bis-ferrocenylpyrazoles via ferrocenylalkylation reaction

Article abstract of DOI:10.1007/s00706-016-1895-3

Abstract: Regioselective synthesis of bis-ferrocenylpyrazole derivatives in biphasic aquatic–organic system under catalysis with HBF₄ was carried out. The regioselectivity of these reactions depending on the electronic effects of substituents i

Full text of DOI:10.1007/s00706-016-1895-3

Monatsh Chem (2017) 148:925–932
DOI 10.1007/s00706-016-1895-3
ORIGINAL PAPER
Synthesis of bis-ferrocenylpyrazoles via ferrocenylalkylation
reaction
Alexey N. Rodionov1
•
Maria D. Gerasimova1 Elena Yu. Osipova1 Alexander A. Korlyukov
•
•
•
Alexander S. Peregudov1 Alexander A. Simenel1
1
•
Received: 21 October 2016 / Accepted: 10 December 2016 / Published online: 23 March 2017
Ó Springer-Verlag Wien 2017
Abstract Regioselective synthesis of bis-ferrocenylpyra-
zole derivatives in biphasic aquatic–organic system under
catalysis with HBF4 was carried out. The regioselectivity
of these reactions depending on the electronic effects of
substituents in pyrazole moiety was studied.
[1–5] and drugs [6] greatly reduced their toxicity. Fur-
thermore, the antitumor activity in vitro and in vivo
[7–14] of ferrocene derivatives was thoroughly studied.
Ferrocenium salts are able to inhibit DNA synthesis by
blocking proliferation [15–17] or by cleavage of the
DNA helix [18]. Besides ferrocene, heterocyclic com-
pounds are effective against mice solid tumors [7, 19]
and human tumor cells [6].
Graphical abstract
A large number of pyrazole derivatives have attracted
lots of attention for the construction of new heterocyclic
compounds [20–25] in which the pyrazole moieties are
used as ligands because of their conjugated heterocycles
and the ability to coordinate metal ions in a variety of
ways, in particular as robust bridging ligands with rigidity
and a moderate acceptor capability [16, 17]. Therefore,
pyrazole derivatives also play a significant role in the field
of functional materials. Ferrocene derivatives of pyrazole
also demonstrate biological activity. The antitumor activity
of amino acid derivatives of ferrocenyl-arylpyrazoles was
studied [26]. Moreover, in [27], bisferrocene pyrazole
derivatives exhibit MLCT (metal to ligand charge transfer)
and p ? p* transitions.
Keywords Metallocenes Á Organometallic compounds Á
Sandwich complexes Á Heterocycles Á
2D NMR spectroscopy Á X-ray structure determination
Introduction
Taking into account the above, we studied the regiose-
lectivity of the alkylation reaction of asymmetrically
substituted pyrazoles 2 and 3a–3d by ferrocenyl carbinols
3a–3d under phase transfer catalysis (HBF4 in aqueous–
organic medium) to synthesize bis-ferrocenylpyrazoles,
containing two active sites in one molecule, which can
together or separately interact with the cell due to the
presence of the labile C–N bond. In this way, the ferro-
cenylalkyl moiety may interact with nucleobases, making
realkylation reaction and blocking DNA transcription and
translation.
Ferrocene derivatives exhibit a wide range of biological
activity. To date, only one ferrocene compound is known
to be used in clinical practice, but along with it there are
many ferrocene derivatives with proved biological
activity. Likewise it was earlier acknowledged that fer-
rocene incorporation in different organic molecules
& Elena Yu. Osipova
jdyotvet@yandex.ru
1
A.N. Nesmeyanov Institute of Organoelement Compounds of
Russian Academy of Sciences, Moscow, Russian Federation
123

926
A. N. Rodionov et al.
carbocations [37–44], which interact with nucleophiles.
Ferrocenylalkylation of moderate strength nitrogen bases
are carried out with equimolar amount of strong acid
(HBF4 or HClO4), but the regioselectivity of this modifi-
cation of ferrocenylalkylation reaction has been
insufficiently investigated to the present.
Results and discussion
Ferrocenylpyrazoles 2a–2d were obtained by the reaction
of 1,3-dicarbonylic derivatives of ferrocene 1b–1d (or its
synthetic analog 1a) with hydrazine hydrate in boiling
ethanol during acetic acid catalysis (Schemes 1, 2).
Ferrocenylalkylation reaction of pyrazoles 2a, 2c pro-
ceeds regioselectively in 50–85% yields, leading to a single
product (Scheme 3). The structures of compounds synthe-
sized (4a–4d and 5a–5d) were assigned based on the data
of 1H and 13C NMR and 1H/13C-heteronuclear correlations.
Particularly in the HMBC spectrum of 1 N-(ferro-
Ferrocenylalkylation reactions in various modifications
are widely used for introducing the ferrocenylalkyl group
in different nucleophiles [28–31]. Obtained in this manner,
nitrogen-containing heterocyclic derivatives possess anti-
tumor activity [2–5] and are the structural units of different
ferrocenyl ligands, which are used in asymmetric catalysis
[32–36]. One of the most convenient and selective method
of ferrocenylalkyl incorporation in different nucleophile
agents, particularly nitrogen-containing heterocycles, is
phase transfer acid-catalyzed ferrocenylalkylation reaction,
the essence of which is to generate stable ferrocenyl
cenylethyl)-3-ferrocenylpyrazole
(4b),
there
are
correlations between quadruplet at 5.41 ppm attributed to
the CH linked to the ferrocene residue, and C-5 carbon
atom of pyrazole (127.2 ppm) and, vice versa, correlation
between the doublet at 7.21 ppm attributed to the C(5)H of
the pyrazole residue and CH linkage carbon atom
(57.06 ppm). There are no correlations between the proton
of CH linkage and C(3) atom of the pyrazole. The struc-
tures of the other bis-ferrocenyl pyrazole derivatives were
proved in the same way. Moreover, the X-ray determina-
tion of molecular and crystal structure of N-
(ferrocenylmethyl)-3-ferrocenylpyrazole (4a) was carried
out. Thus, ferrocenylalkylation of 3-ferrocenylpyrazole and
3-ferrocenyl-5-methylpyrazole proceeds in the most remote
position from the bulky ferrocenyl residue. The alkylation
of this nitrogen atom is not sterically hindered (Fig.1).
Earlier, it was shown that ferrocenylalkylation under
phase transfer catalysis of asymmetrically substituted
heterocycles is generally dependent on the electronic
effects of substituents [45] and proceeds in the position
most remote from strong electron-withdrawing groups. It
was proven by our results on ferrocenylalkylation of
3-ferrocenyl-5-(trifluoromethyl)pyrazole in methylene
dichloride with various ferrocenylcarbinols in the presence
of aqueous tetrafluoroboronic acid (Scheme 4).
Scheme 1
O
N
N
N
H
.
NH2NH2 H2O
Fe
Fe
EtOH
1a
2a
The structures of the compounds synthesized (6a–6d)
were assigned in the same way. Ferrocenylalkylation of
123

Synthesis of bis-ferrocenylpyrazoles via ferrocenylalkylation reaction
927
Fig. 1 Molecular
cenylpyrazole (4a)
structure
of
N-(ferrocenylmethyl)-3-ferro-
3-ferrocenyl-5-(trifluoromethyl)pyrazole proceeds in the
position most remote from the electron-withdrawing group
(CF3). Thus, the direction of alkylation in this case was
determined by the electronic effects of the trifluoromethyl
substituent (Figs. 2, 3).
Fig. 2 Molecular
cenylpyrazole (6a)
structure
of
N-(ferrocenylmethyl)-3-ferro-
X-ray
X-ray diffraction studies of 4a, 6a, and 6b have revealed that
the bond length and the angles of the pyrazole and ferrocene
moieties vary in ranges that are typical for compounds of
similar types. The presence of CF3 groups led to minor
shortening of the C–C bond in the pyrazole ring of 6a and 6b
as compared to 4a. Besides, in 6a and 6b, the ferrocenyl
substituents are very close to each other and the repulsion
between those bulky groups caused slight elongation of the
However, the ferrocenylalkylation reaction of 3-(car-
boxyethyl)-5-ferrocenylpyrazole (2d) under phase transfer
catalysis proceeds on both nitrogen atoms, and the ratio of
the products of alkylation is approximately 1:1 (Scheme 5).
This indicates that the ester group has a weaker electron-
withdrawing effect than the CF3 group, and the two factors
(electronic and steric) influence the selectivity of the
alkylation reaction in aqueous–organic media.
123

928
A. N. Rodionov et al.
substituents in pyrazole, the steric factor plays a leading
role. In case of electron-withdrawing ones, the regiose-
lectivity depends on the strength of the substituent.
Experimental
The solvents were purified by standard techniques. Ferro-
cenylmethanol
3a
was
obtained
from
trimethylferrocenylmethylammonium iodide according to a
well-known procedure [46]. Other ferrocenylcarbinols 3b–
3d were synthesized from the corresponding acylferrocenes
by reduction with lithium aluminum hydride in THF
[2, 47, 48]. Ferrocenyl containing b-diketone and their
synthetic analogs were synthesized by the modified method
[49].
Melting points were determined with a Stuart Scientific
SMP30. 1H and 13C NMR spectra were recorded on Bruker
DRX-400 and Bruker DRX-500 spectrometers at 400.13
(500.13) MHz and 100 (125.76) MHz for protons and 13C,
respectively, at 30 °C in CDCl3. Chemical shifts (d) are
reported in ppm relative to CHCl3 (7.28 and 77.00 ppm for
1H and 13C, respectively). 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 spectrophotometer using a KBr disk.
EI mass spectra were taken on a Finnigan Polaris Q
Fig. 3 Molecular structure of N-(ferrocenylethyl)-3-ferrocenylpyra-
zole (6b)
˚
N1–C1 bond (by 0.03–0.04 A, Table 1) in comparison with
4a where the ferrocenyl substituents is N1 and C2 atoms.
Conclusion
In summary, we studied the regioselectivity of the ferro-
cenylalkylation reaction in acid phase transfer catalysis to
produce bis-ferrocenylpyrazoles. In the case of donating
Scheme 5
Et
COO
Et
COO
Et
COO
N
N
NH
N
N
H
N
O
Fc
+
HBF4
+
Fe
Fe
Fe
Fe
Fc
H
l
C
2C 2
8a
7a
2d
3a
Table 1 Selected bond length
˚
in 4a, 6a, and 6b/A
4a
6a
6b
N1–N2
N1–C1
N2–C3
N2–C14
C1–C2
C2–C3
C1–C4
1.3579 (17)
1.3359 (19)
1.351 (2)
N1–N2
N1–C1
N1–C15
N2–C3
C1–C2
C2–C3
C3–C4
1.345 (5)
1.368 (5)
1.473 (5)
1.334 (5)
1.391 (5)
1.396 (6)
1.488 (6)
N1–N2
N1–C1
N1–C5
N2–C3
C1–C2
C1–C17
C3–C4
1.3510 (14)
1.3708 (14)
1.4717 (14)
1.3296 (15)
1.3901 (16)
1.4625 (16)
1.4895 (17)
1.4524 (19)
1.410 (2)
1.366 (2)
1.457 (2)
123

Synthesis of bis-ferrocenylpyrazoles via ferrocenylalkylation reaction
929
Uiso(H) = 1.5Ueq(CH3)]. Preparation of graphic materials
was performed using the OLEX2 software package [54].
Crystallographic data for the structural analysis of 4a, 6a,
and 6b have been deposited with the Cambridge Crys-
Table 2 Crystallograhic data and experimental parameters of X-ray
study of compounds 4a, 6a, and 6b
4a
6a
6b
Brutto formula
Formula weight
Space group
Z
C24H22Fe2N2 C25H21F3Fe2N2 C26H23F3Fe2N2
tallographic
Data
Centre
(CCDC
Nos.
450.13
P21/c
4
518.14
P-1
2
532.16
1484643–1484646).
P-1
2
General procedure for the synthesis
of ferrocenylpyrazoles [55, 56]
˚
a/A
13.3166 (7) 8.9664 (18)
9.6370 (5) 10.044 (2)
14.9582 (8) 12.220 (2)
9.5257 (6)
10.5762 (7)
12.2530 (8)
113.1730 (10)
90.8330 (10)
˚
b/A
˚
c/A
To ferrocenyl containing b-diketone (10 mmol) dissolved
in 100 cm3 alcohol, 0.85 cm3 hydrazine hydrate (85%,
15 mmol) was added with continuous stirring. Afer
refluxing for 4 h, the solvent was removed in vacuum, and
the residue was recrystallized from aqueous ethanol (90%).
a/°
b/°
90
77.183 (4)
72.266 (4)
101.0400
(10)
c/°
V/A
90
88.884 (4)
105.8490 (10)
1081.26 (12)
1.635
3
˚
1884.09 (17) 1020.8 (4)
d
calc/g cm-3
1.587
15.52
928
1.686
14.64
528
3-Ferrocenyl-1H-pyrazole (2a)
Yield: 87%; brown crystals; m.p.: 145 °C (Ref. [55, 56]
146 °C).
l/cm-1
U (000)
2hlan/°
13.85
544
52
52
52
3-Ferrocenyl-5-(trifluoromethyl)-1H-pyrazole (2b)
Yield: 82%; orange crystals; m.p.: 160 °C (Ref. [27]
160 °C).
Reflections
collected
30,385
10,511
14,515
Independent
reflections
7389
5885
4441
2940
6635
6053
3-Ferrocenyl-5-methyl-1H-pyrazole (2c)
Yield: 85%; dark yellow crystals; m.p.: 162–163 °C (Ref.
[57, 58] 164 °C).
Reflections with
I [ 2r(I)
Parameters
253
289
299
Ethyl 3-Ferrocenyl-1H-pyrazole-5-carboxylate (2d)
Yield: 89%; dark orange crystals; m.p.: 196–198 °C (Ref.
[59, 60] 197 °C).
R1 [I [ 2r(I)]
wR2 (all indep.
reflections)
0.0356
0.0922
0.0463
0.1196
0.0268
0.0696
GOF
1.044
0.868
1.053
General procedure for alkylation
of ferrocenylpyrazoles
Residual electron
density/
0.713/-0.304 1.834/-0.663 0.459/-0.568
e A-3(qmin/qmax
)
˚
To a mixture of 1.0 mmol ferrocenyl alcohol and 1.0 mmol
of the corresponding pyrazoles in 1 cm3 of methylene
chloride, 0.18 cm3 of 48% aqueous fluoroboric acid
(1.0 mmol) was added with vigorous stirring. Stirring was
continued for 5–10 min after which 10 cm3 of water and
10 cm3 of diethyl ether were added. The resulting mixture
was washed with water (2 9 15 cm3) and the organic layer
was separated and dried over CaCl2. The solvent was
removed in vacuo.
spectrometer at 70 eV and the temperature of the ion
chamber was 250 °C.
Single crystals suitable for X-ray diffraction analysis
were obtained by recrystallization from chloroform. X-ray
diffraction measurements were carried out using Bruker
Smart 1000 CCD and Bruker Smart Apex II CCD
diffractometers at 120 K. The frames were integrated
using APEX2 program packages [50]. The correction for
absorption was made using the SADABS program [51].
The selected bond lengths are summarized in Table 1,
while the details of crystallographic data and experi-
mental conditions are given in Table 2. The structures
were solved by the direct method by SHELXT program
[52] and refined by full-matrix least-squares technique
against F2 in the anisotropic–isotropic approximation
using SHELXL program [53]. All hydrogen atoms were
placed in geometrically calculated positions and refined in
rigid body model [Uiso(H) = 1.2Ueq(CH, CH2),
1-(Ferrocenylmethyl)-3-ferrocenyl-1H-pyrazole
(4a, C24H22Fe2N2)
Yield 67%; bronze oil; 1H NMR (400 MHz, CDCl3):
d = 7.26 (d, J = 2 Hz, 1H, Pz), 6.27 (d, J = 2 Hz, 1H,
Pz), 5.07 (s, 2H, CH2), 4.70 (s, 2H, Fc), 4.30 (s, 2H, Fc),
4.27 (s, 2H, Fc), 4.20 (m, 7H, Fc), 4.09 (s, 5H, Fc) ppm;
13C NMR (100 MHz, CDCl3): d = 148.8, 128.2, 103.3,
84.3, 79.4, 69.4, 68.9, 68.3, 68.2, 68.0, 66.5, 48.6 ppm; MS
(70 eV): m/z = 450 (M?, 100).
123

930
A. N. Rodionov et al.
3-Ferrocenyl-1-(1-ferrocenylethyl)-1H-pyrazole
(4b, C25H24Fe2N2)
5-Methyl-1-(1-ferrocenylethyl)-3-ferrocenyl-1H-
pyrazole (5b, C26H26Fe2N2)
1
Yield 60%; dark orange oil; H NMR (400 MHz, CDCl3):
Yield 46%; orange oil; 1H NMR (400 MHz, CDCl3):
d = 6.05 (s, 1H, Pz), 5.27 (q, J = 7 Hz, 1H, CH), 4.73 (s,
1H, Fc), 4.64 (s, 1H, Fc), 4.29 (s, 1H, Fc), 4.24 (s, 2H, Fc),
4.22 (s, 5H, Fc), 4.13–4.17 (m, 2H, Fc), 4.08 (s, 5H, Fc),
4.04 (s, 1H, Fc), 2.23 (s, 3H, CH3), 1.86 (d, J = 7 Hz, 3H,
CH3) ppm; 13C NMR (100 MHz, CDCl3): d = 148.2,
137.9, 103.2, 90.9, 79.8, 69.5, 69.0, 68.2, 67.4, 67.2, 66.7,
66.6, 66.5, 53.8, 20.8, 11.7 ppm; MS (70 eV): m/z = 478
(M?, 99).
d = 7.20 (d, J = 2.2 Hz, 1H, Pz), 6.25 (d, J = 2.2 Hz, 1H,
Pz), 5.38 (q, J = 7 Hz, 1H, CH), 4.71 (m, 2H, Fc),
4.26–4.24 (m, 4H, Fc), 4.19 (m, 7H, Fc), 4.08 (s, 5H, Fc),
1.83 (d, J = 7 Hz, 3H, CH3) ppm; 13C NMR (100 MHz,
CDCl3): d = 149.3, 127.3, 102.8, 89.4, 79.3, 69.5, 69.0,
68.5, 68.3, 67.8, 67.7, 66.6, 66.5, 66.3, 57.2, 21.7 ppm; MS
(70 eV): m/z = 464 (M?, 97).
3-Ferrocenyl-1-(1-ferrocenylbenzyl)-1H-pyrazole
(4c, C30H26Fe2N2)
5-Methyl-1-(1-ferrocenylbenzyl)-3-ferrocenyl-1H-
pyrazole (5c, C31H28Fe2N2)
1
Yield 80%; red-brown oil; H NMR (400 MHz, CDCl3):
d = 7.33–7.27 (m, 3H, Ph), 7.22 (d, J = 2.2 Hz, 1H, Pz),
7.20–7.18 (m, 2H, Ph), 6.52 (s, 1H, CH), 6.31 (d,
J = 2.2 Hz, 1H, Pz), 4.77 (s, 1H, Fc), 4.70 (s, 1H, Fc), 4.27
(s, 2H, Fc), 4.27–4.24 (m, 5H, Fc), 4.19 (s, 5H, Fc), 4.11 (s,
1H, Fc), 4.07 (s, 5H, Fc) ppm; 13C NMR (100 MHz,
CDCl3): d = 149.8, 141.0, 129.3, 128.4, 127.8, 127.5,
103.1, 88.0, 79.2, 69.6, 69.3, 69.0, 68.6, 68.4, 68.1, 67.7,
66.9, 66.5, 65.7, 53.6 ppm; MS (70 eV): m/z = 526 (M?,
93).
Yield 61%; orange crystals; m.p.: 144 °C; 1H NMR
(400 MHz, CDCl3): d = 7.15–7.45 (m, 5H, Ph), 6.35 (s,
1H, Pz), 6.13 (s, 1H, CH), 4.74 (s, 2H, Fc), 4.62 (s, 1H, Fc),
4.26 (m, 4H, Fc), 4.21 (s, 1H, Fc), 4.14 (s, 1H, Fc), 4.12 (s,
5H, Fc), 4.09 (s, 5H, Fc), 2.22 (s, 3H, CH3) ppm; 13C NMR
(100 MHz, CDCl3): d = 148.6, 141.3, 138.8, 128.3, 127.4,
127.3, 103.4, 88.8, 69.5, 69.1, 68.7, 68.5, 68.3, 67.5, 66.7,
62.4, 12.2 ppm; MS (70 eV): m/z = 540 (M?, 91).
5-Methyl-1-(2-methyl-1-ferrocenylpropyl)-3-
ferrocenyl-1H-pyrazole (5d, C28H30Fe2N2)
1-(2-Methyl-1-ferrocenylpropyl)-3-ferrocenyl-1H-
pyrazole (4d, C27H28Fe2N2)
Yield 85%; red crystals; m.p.: 130 °C; 1H NMR
(400 MHz, CDCl3): d = 7.48 (s, 1H, Pz), 6.38 (s, 1H, Pz),
4.78 (s, 2H, Fc), 4.55 (s, 1H, Fc), 4.40 (s, 1H, Fc), 4.30 (s,
2H, Fc), 4.22 (s, 2H, Fc), 4.10 (s, 5H, Fc), 3.96 (s, 5H, Fc),
2.17 (m, 1H, CH), 0.84 (d, J = 8 Hz, 3H, CH3), 0.74 (d,
J = 8 Hz, 3H, CH3) ppm; 13C NMR (100 MHz, CDCl3):
d = 194.6, 171.3, 117.7, 93.3, 91.2, 91.2, 78.6, 74.5, 69.8,
68.5, 67.4, 66.7, 66.3, 53.5, 46.8, 21.7, 14.5 ppm; MS
(70 eV): m/z = 506 (M?, 90).
Yield 71%; orange crystals; m.p.: 139 °C; 1H NMR
(400 MHz, CDCl3): d = 7.48 (s, 1H, Pz), 6.38 (s,1H, Pz),
4.78 (s, 2H, Fc), 4.55 (d, J = 9.4 Hz, 1H, CH), 4.40 (s, 1H,
Fc), 4.30 (s, 2H, Fc), 4.23 (s, 1H, Fc), 4.20 (s, 1H, Fc),
4.13–4.10 (m, 6H, Fc), 3.96 (s, 5H, Fc), 2.22–2.13 (m, 1H,
CH), 0.84 (d, J = 6.6 Hz, 3H, CH3), 0.74 (d, J = 6.6 Hz,
3H, CH3) ppm; 13C NMR (100 MHz, CDCl3): d = 148.8,
128.9, 102.7, 89.7, 79.8, 70.0, 69.5, 69.0, 68.8, 68.4, 68.3,
68.2, 66.8, 66.7, 66.6, 66.5, 36.4, 20.5, 20.1 ppm; MS
(70 eV): m/z = 492 (M?, 100).
1-(Ferrocenylmethyl)-5-ferrocenyl-3-
(trifluoromethyl)-1H-pyrazole (6a, C25H21F3Fe2N2)
5-Methyl-1-(ferrocenylmethyl)-3-ferrocenyl-1H-
pyrazole (5a, C25H24Fe2N2)
Yield 83%; orange crystals; m.p.: 165 °C; 1H NMR
(400 MHz, CDCl3): d = 6.58 (s, 1H, Pz), 5.15 (s, 2H,
CH2), 4.50 (s, 2H, Fc), 4.38 (s, 2H, Fc), 4.20 (s, 5H, Fc),
4.15 (s, 5H, Fc), 4.12 (m, 4H, Fc) ppm; 13C NMR
(100 MHz, CDCl3): d = 142.3, 141.2 (q, J = 38 Hz,
C(Pz)), 121.5 (q, J = 269 Hz, CF3), 104.3, 83.6, 74.1,
69.8, 69.2, 68.9, 68.3, 68.0, 49.7 ppm; MS (70 eV): m/
z = 518 (M?, 95).
Yield 50%; orange crystals; m.p.: 152 °C; 1H NMR
(400 MHz, CDCl3): d = 6.05 (s, 1H, Pz), 4.99 (s, 2H,
CH2), 4.66 (s, 2H, Fc), 4.22–4.25 (m, 7H, Fc), 4.08–4.14
(m, 7H, Fc), 2.29 (s, 3H, CH3) ppm; 13C NMR (100 MHz,
CDCl3): d = 148.8, 138.2, 103.3, 84.3, 79.4, 69.4, 68.9,
68.3, 68.2, 68.0, 66.5, 48.7, 11.4 ppm; MS (70 eV): m/
z = 464 (M?, 100).
123

Synthesis of bis-ferrocenylpyrazoles via ferrocenylalkylation reaction
931
1-(1-Ferrocenylethyl)-5-ferrocenyl-3-
(trifluoromethyl)-1H-pyrazole (6b, C26H23F3Fe2N2)
Ethyl 1-(ferrocenylmethyl)-3-ferrocenyl-1H-pyrazole-
5-carboxylate (8a, C27H26Fe2N2O2)
Yield 51%; orange powder; m.p.: 157 °C; 1H NMR
(400 MHz, CDCl3): d = 6.59 (s, 1H, Pz), 5.53 (q,
J = 7 Hz, 1H, CH), 4.54 (s, 1H, Fc), 4.47 (s, 1H, Fc), 4.39
(s, 2H, Fc), 4.23 (s, 1H, Fc), 4.22 (s, 5H, Fc), 4.16 (s, 1H,
Fc), 4.12 (s, 5H, Fc), 3.89 (s, 1H, Fc), 1.84 (d, J = 7 Hz,
3H, CH3) ppm; 13C NMR (100 MHz, CDCl3): d = 141.9,
103.9, 91.2, 76.9, 74.5, 69.8, 69.4, 69.2, 69.0, 68.9, 68.1,
67.0, 66.9, 66.7, 53.5, 21.7 ppm; MS (70 eV): m/z = 532
(M?, 97).
Yield 27%; orange crystals; m.p.: 139 °C; 1H NMR
(500 MHz, CDCl3): d = 6.88 (s, 1H, Pz), 5.20 (s, 2H,
CH2), 4.49 (s, 2H, Fc), 4.44 (q, J = 7.1 Hz, 2H, CH2),
4.37 (s, 2H, Fc), 4.19 (s, 5H, Fc), 4.14 (s, 5H, Fc), 4.11
(s, 2H, Fc), 4.09 (s, 2H, Fc), 1.43 (t, J = 7.1 Hz, 3H,
CH3) ppm; 13C NMR (125 MHz, CDCl3): d = 162.7,
142.3, 142.1, 109.0, 83.5, 74.5, 69.8, 69.3, 69.1, 68.9,
68.5, 68.0, 60.9, 50.0, 14.5 ppm; MS (70 eV): m/z = 522
(M?, 74).
Acknowledgements The reported study was funded by the Russian
Foundation for Basic Research (RFBR), according to the research
project No. 16-33-60163 (mol_a_dk).
5-Ferrocenyl-1-(1-ferrocenylbenzyl)-3-
(trifluoromethyl)-1H-pyrazole (6c, C31H25F3Fe2N2)
Yield 51%; orange powder; m.p.: 169 °C; 1H NMR
(400 MHz, CDCl3): d = 7.23–7.31 (m, 3H, Ph), 7.14 (d,
J = 7 Hz, 2H, Ph), 6.70 (s, 1H, Pz), 6.47 (s, 1H, CH), 4.65 (s,
1H, Fc), 4.60 (s, 1H, Fc), 4.51 (s, 1H, Fc), 4.44 (s, 2H, Fc),
4.25 (s, 5H, Fc), 4.18 (s, 1H, Fc), 4.16 (s, 1H, Fc), 4.08 (s, 1H,
Fc), 3.94 (s, 5H, Fc) ppm; 13C NMR (100 MHz, CDCl3):
d = 142.9, 141.3 (q, J = 38 Hz, C(Pz)), 140.9, 135.5,
128.4, 127.5, 127.0, 121.6(q, J = 269 Hz, CF3), 104.2, 89.1,
74.6, 69.9, 69.8, 69.6, 69.5, 69.3, 69.2, 69.1, 68.7, 68.5, 66.9,
61.5, 29.7 ppm; MS (70 eV): m/z = 594 (M?, 100).
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