Ferrocenyl pyrazolines: Preparation, structure, redox properties and DFT study on regioselective ring-closure

Article abstract of DOI:10.1016/j.jorganchem.2009.09.007

Cyclocondensation of 1-phenyl-3-ferrocenyl-2-propen-1-one (1) with RNHNH2 hydrazines and the substituent-dependent product distribution were investigated. With methylhydrazine, formation of two regioisomeric pairs of pyrazolines and pyrazoles was observed

Full text of DOI:10.1016/j.jorganchem.2009.09.007

Journal of Organometallic Chemistry 694 (2009) 4185–4195
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Ferrocenyl pyrazolines: Preparation, structure, redox properties and DFT study
on regioselective ring-closure q
Virág Zsoldos-Mády a, Oliver Ozohanics b, Antal Csámpai b, Veronika Kudar b, Dávid Frigyes b, Pál Sohár a,b,
*
a Protein Modelling Group, Hungarian Academy of Sciences, Eötvös Loránd University, H-1518 Budapest 112, POB 32, Hungary
b Institute of Chemistry, Department of Inorganic Chemistry, Eötvös Loránd University, H-1518 Budapest 112, POB 32, Hungary
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 14 July 2009
Received in revised form 27 August 2009
Accepted 3 September 2009
Available online 10 September 2009
Cyclocondensation of 1-phenyl-3-ferrocenyl-2-propen-1-one (1) with RNHNH2 hydrazines and the sub-
stituent-dependent product distribution were investigated. With methylhydrazine, formation of two reg-
ioisomeric pairs of pyrazolines and pyrazoles was observed. The ratio of the products varied with the
solvent and temperature. Transformation of 5-ferrocenyl-N-substituted pyrazolines into pyrazoles was
systematically studied and DDQ was found to be the most suitable reagent. Mechanism of the cyclization
reactions taking place under kinetic- and thermodynamic controls was supported with DFT calculations.
The energy-dependence of the transformation of pyrazoline to pyrazole was investigated also by EI MS.
Structure determination of the new compounds was performed by IR, MS and NMR methods including
2D-HMQC, 2D-HMBC, DEPT and DIFFNOE measurements. For two compounds structures were also
proved by X-ray diffraction.
Keywords:
Ferrocenes
Pyrazoles
NMR
X-ray
Ó 2009 Elsevier B.V. All rights reserved.
MS and IR study
DFT calculation
1. Introduction
group also several ferrocene containing pyrazole derivatives were
recently prepared as potential biologically active molecules [7,13–
Among the nitrogen heterocycles the 1-H pyrazoles and their
4,5-dihydro-derivatives have outstanding synthetic and biological
significance [2]. Some of them have antibacterial, antimycotic or
anticancer effect and several 1,3,5-triaryl-pyrazoles are used as
anti-inflammatory and anti-rheumatic agents [2,3]. Recently new
pyrazole derivatives were prepared as reverse transcriptase inhib-
itors for the treatment of HIV disorders [4]. Several 1-methyl-3,5-
15].
Earlier studies indicated, that cyclocondensation of diaryl-
propenones with hydrazines may lead to pyrazolines and/or pyra-
zoles, depending on the reaction conditions [2,16]. The present
work aimed detailed investigation on the formation of ferrocenyl
pyrazolines having different substituents at N ꢀ 1, starting from
the easily available 3-ferrocenyl-1-aryl-propenones. Furthermore,
we aimed a comparative study on the transformation of the pyraz-
olines into the corresponding pyrazoles. The experimental results
were supported also by DFT calculations. As the stereochemistry
has an important role in bioactivity, to clear the 3D-structures
NMR-measurements, and in the case of some molecules also
X-ray analysis were carried out.
diaryl-pyrazoles were patented as c-secretase inhibitors and were
claimed useful for the treatment of Alzheimer’s disease [5]. Fur-
thermore, series of substituted phenylpyrazoles were developed
as very effective and selective inhibitors of factor Xa, an important
serine protease [6].
4,5-Dihydro-1-H-pyrazoles can be prepared advantageously by
reacting 1,10-diaryl-prop-2-en-1-ones (chalcones, Ar–CH@CH–CO–Ar0)
with hydrazine derivatives [2,7,8]. Incorporation of the three-
dimensional ferrocenyl group instead of a flat aryl or hetaryl substi-
tuent into the molecule can result in favourable change of biological
properties [9–11]. Ferrocenyl-substituted pyrazoles are intensively
studied nowadays by numerous research groups [6,8,10,12]. In our
2. Results and discussion
2.1. Syntheses
Reaction of 3-ferrocenyl-1-phenyl-prop-2-en-1-one (1) with
aqueous hydrazine in ethanol resulted in 5-ferrocenyl-3-phenyl-
4,5-dihydro-1H-pyrazole (2a) in good yield, in accordance with
earlier findings [17]. These types of pyrazolines with free NH group
were described occasionally as unstable materials, but they are
more stable in the dry state [8]. Acetylation of 2a can be advanta-
q
Study on ferrocenes, Part 23. Part 22. See Ref. [1].
* Corresponding author. Address: Protein Modelling Group, Hungarian Academy
of Sciences, Eötvös Loránd University, H-1518 Budapest 112, POB 32, Hungary. Tel.:
+36 1 372 2911; fax: +36 1 372 2592.
E-mail address: sohar@chem.elte.hu (P. Sohár).
0022-328X/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2009.09.007

4186
V. Zsoldos-Mády et al. / Journal of Organometallic Chemistry 694 (2009) 4185–4195
geously carried out with acetic anhydride in pyridine at 0 °C,
resulting in the stable N-acetyl derivative 2b in good yield (Scheme
1). We found this mild acetylation method a good alternative to
previous procedures which used boiling acetic anhydride for the
preparation of N-acetyl-pyrazolines [17,18].
The N-phenyl-pyrazoline 2c was prepared by reacting 1 with
phenylhydrazine in acetic acid–ethanol–water [18a], and the new
N-(p-nitrophenyl)-pyrazoline (2d) was prepared analogously. In
this latter case a 4-hydroxylated pyrazoline (11) as by-product
could also be isolated. Formation of 11 can be explained by radical
oxidation in the presence of p-nitrophenylhydrazine having been
in excess in the reaction mixture.
To find the best procedure for the transformation of ferrocenyl-
pyrazolines to pyrazoles, compounds 2c and 2d were used as mod-
el compounds. A variety of reagents were published for the dehy-
droaromatisation of pyrazolines [2,19], but in our case – because
of the sensitivity of the ferrocenyl group to oxidation – only some
of the methods seemed to be applicable. Our first attempts, to carry
out the transformation of pyrazolines with N-bromo-succinimide
(NBS) in analogous circumstances as described [20], gave poor re-
sults. By reacting 2c with NBS in carbon tetrachloride as solvent,
using pyridine as base, 3c was formed in 29% yield even with a sig-
nificant excess of the reagent. From 2d the pyrazole 3d was iso-
lated only in 8% yield with NBS. Next, we tried the
dehydroaromatisation of 2c by sonication-assisted oxidation with
copper(II) nitrate trihydrate, which has recently been published
as advantageous reagent for such type of transformations [21].
However, employing this method, 3c could be prepared only in
moderate yield (37%).
aromatisation propensity of 5-ferrocenyl-3-phenyl pyrazolines
2b–d. The N-phenyl-derivative 2c reacted smoothly with 1.2 equiv.
of DDQ even at RT, in dichloromethane or in benzene solution and
gave the desired pure, crystalline pyrazole 3c in about 80% yield.
The progress of the reaction could be followed visually not only
by TLC, but also by the amount of the precipitated greyish-green so-
lid (quinone–hydroquinone-type complex). Under similar condi-
tions 2d did not react at all, even after addition of 2.0 equiv. of
DDQ to the mixture. However, in toluene at reflux temperature, in
the presence of 1.2 equiv. of DDQ, the reaction was complete within
2 h and 3d could be isolated after purification in 76% yield. The N-
acetyl-pyrazoline 2b reacted also moderately, the dehydroaromat-
isation has been carried out only at higher temperature (ꢁ80 °C) in
benzene or in toluene solution, by gradual addition of the solution
of 1.3 equiv. of DDQ, and pyrazole 3b was isolated in 42% yield.
From our findings it can be seen, that pyrazolines 2b and 2d, having
electron-withdrawing substituent at the N atom, show decreased
reactivity towards oxidation with DDQ in non-polar solvents.
We investigated the reaction of 1 with methylhydrazine, too,
under different conditions and observed formation of more com-
plicated mixtures. Two regioisomeric pairs of N-methyl-pyrazo-
lines (2e and 4e) and N-methyl-pyrazoles (3e and 5e) could be
identified as hitherto unknown new compounds, but the ratio of
the products varied depending on the solvent and temperature.
All reactions were conducted under nitrogen. In boiling ethanol,
with 6.5 equiv. of methylhydrazine (added in two portions), the
main isolated products were 5-ferrocenyl-pyrazoline 2e (23%
yield) and 3-ferrocenyl-pyrazole 5e (43% yield). Although the ‘‘re-
verse” 3-ferrocenyl-pyrazoline (4e) could be indicated by TLC in
notable amount in the mixture, during work-up and purification
a significant part of that was transformed into the corresponding
pyrazole 5e even when chromatography on Silica gel was made
As quinone-type reagents in some cases proved to be also suit-
able for oxidation of pyrazolines [2,14,19,22], we resorted to 2,3-di-
chloro-5,6-dicyano-1,4-benzoquinone (DDQ) and investigated the
R
R
C
N
N
N
N
Fe
R'
Fe
R'
A
B for
b-type
R
R'
R'NHNH2
compd.
R
R
R'
H
H
2a
2b
2c
H
H
H
H
Ac
Ph
p-NO2-Ph
Me
Ph
Ph
α-Py
p-NO2-Ph
H
Ac
Ph
p-NO2-Ph
Me
Ph
3b
3c
3d
3e
8a
H
H
H
2d
2e
CO
Fe
p-OH
7a
7b
9b
10b
p-OH
8b p-OAc
p-OAc
p-OAc
p-OAc
Ph
1
6
(R = H)
(R = OH)
A
R'NHNH2
D
HO
N
N
N
N
N
N
Fe
Me
Me
Fe
Fe
NO2
4e
5e
11
Reaction conditions:A) Hydrazinolysis of 1 or 6 with RNHNH2: EtOH, RT for 2a; AcOH, reflux for 2b; AcOH-EtOH-H2O, reflux for 2c, 2d,
7a+8a, 9a, 10a; MeOH, 40oC for 2e-5e; toluene, reflux for 4e+5e; B) Acetylation of 2a, 7a, 9a and 10a to 2b, 7b, 9b and 10b with Ac2O in
pyridine at 0oC; C) Dehydroaromatization of pyrazolines 2 to pyrazoles 3 a) with Cu(NO3)2.3H2O under sonication, CH2Cl2 for 3c; b) N-bromo-
succinimide, CCl4, reflux for 3c and 3d; c) DDQ, CH2Cl2 or toluene, RT for 3c; toluene, reflux for 3b, 3d and 8b; partial spontaneous oxidation
during the reaction for 8a, 3e and 5e; D) 11: by-product at the preparation of 2d.
Scheme 1.

V. Zsoldos-Mády et al. / Journal of Organometallic Chemistry 694 (2009) 4185–4195
4187
under nitrogen. During purification of the yellow crude products
reconversion to chalcone 1 was also observed. This fact indicates
that some of the first steps of the reaction should be reversible.
When reaction of 1 was carried out with 6.5 equiv. of meth-
ylhydrazine in methanol below 40 °C, the main product was 2e.
In the next experiment, the solvent was changed to toluene, and
solution of methylhydrazine (5.5 equiv.) was added to the boiling
solution of 1 in two portions. In that case the main product was
the ‘‘reverse” pyrazoline 4e and during the reaction the amount
of 5e was gradually increasing. During purification by column
chromatography this spontaneous dehydroaromatisation process
was continued, affording 5e in 58% yield, while 4e was isolated
in pure form only in 8% yield. The regioisomeric 2e and 3e were
present only in a fewer amount. Our observations suggest that 1-
methyl-3-ferrocenyl-pyrazoline 4e is formed under thermody-
namic control.
keeping with our preparative experiments, the results (
R
c2
=
LUMO
0.193 for C-b and 0.150 for C@O) suggest that 1 has increased reac-
tivity on the b-carbon atom in the orbital-controlled [28] addition
towards the more nucleophilic methylated nitrogen of methylhydr-
azine (R
c2HOMO = 0.244 on NHMe and 0.076 on NH2 as calculated by
the same method).
Corroborating with the formation of 4e at elevated temperature,
the free energy data obtained for the primary adducts (I–IV,
R0 = Me, Ar = Ph, Scheme 2, Table 1) suggest that under thermody-
namic control the reaction of 1 and methylhydrazine must proceed
along pathway D via the most stable adduct IV with slightly in-
creased entrophy resulted from nucleophilic attack of the NH2
group on the b-carbon atom, which undergoes cyclocondensation
and sequentional tautomerization affording the pyrazoline with
reversed substitution pattern (IV ? VIII ? IX ? X ? 4e). The rela-
tive free energy values also demonstrate that allyl alcohol type
intermediates II and III formed upon the addition on the carbonyl
group of 1 are less stable by ca 55–75 kJ/mol than the b-adducts
referring to the little contribution of pathways 1 ? II ? VI ? 2e
and 1 ? III ? VII ? 4e, respectively, to the formation of pyrazoline
products.
In principle alternative pathways B and C can not be ruled out
completely for the formation of 2a–e, 7a,b and 4e, respectively,
but they might play only negligible roles in these cyclization
reactions.
The regioisomeric pyrazolines (2e and 4e), both in crude mix-
ture or in isolated crystalline form, were transformed into the cor-
responding pyrazole compounds (3e and 5e) with DDQ in good
yield.
2.1.1. DFT study on cyclization reactions
In order to propose reaction mechanisms being in accord with
our experimental observations, four possible pathways (A–D,
Scheme 2) were taken into account for the formation of pyrazolines
with alternative substitution patterns. On the basis of our earlier re-
sults [15] it can be assumed that cyclizations conducted at lower
temperature in protic media take place along pathway A via the fast
orbital-controlled conjugate addition of the substituted nitrogen
leading to b-adducts type I of which cyclization and subsequent
dehydration result in 3-ferrocenyl-pyrazolines (I ? V ? 2a–e,
7a,b). By means of theoretical modelling of simplified models (1-
arylprop-2-en-1-ones) we have earlier shown [15] that kinetically
controlled cyclization of neutral chalcones with methylhydrazine
proceeds through b-adducts analogous to I. Following the same
way of interpretation, employing simple FMO theory [23] within
the frame of DFT [24] which proved to be sufficient to account for
positional selectivity [15,25], the local electrophilicity inside the
enon moiety was characterized by the relevant LUMO electron
deficiency values concentrated on the potential electrophilic centra
It is noteworthy, that pyrazoline ? pyrazole transformation
was also observed during MS measurements of several models
(see later).
In order to get new ferrocenyl-aryl-heterocycles having func-
tionalisable groups at the phenyl moiety and also for biological
purposes, some further pyrazoline derivatives were prepared. From
3-ferrocenyl-1-(p-hydroxyphenyl)-prop-2-en-one (6) [14] with
4.5 equiv. of phenylhydrazine in boiling acetic acid–ethanol–water
mixture the N-phenyl-5-ferrocenyl-pyrazoline derivative (7a) was
(
R
c2LUMO on C-b and C@O) in the optimized structure of 1 obtained
at B3LYP level of theory [26] using 6ꢀ31G(d,p) basis set [27]. In
Fc
Ar
Ar
Fc
-H2O
-2H
OH
2a-e, 7a-b
3e, 8a
O
N
N
NH
R'
R'
NH2
I
V
A
NH2NHR'
-H2O
Ar
Ar
Fc
Fc
Fc
fast
B
C
NH-NHR'
HO
II
N
R'HN
VI
β
Ar
Fc
O
5e
-2H
4e
1, 6
-H2O
Ph
Fc
Ph
N(Me)-NH2
N
HO
HN
Me
NH2NHMe
slow
III
VII
D
Ph
Ph
Fc
Fc
Fc
Ph
Fc
Ph
-H2O
OH
Me
N
O
HN
IX
N
HN
N
HN
VIII
N
Me
H
Me
MeHN
IV
X
Ar = Ph, p-HO-Ph; R' = H, Me, Ph, p-NO2-Ph, α-Py
Scheme 2.

4188
V. Zsoldos-Mády et al. / Journal of Organometallic Chemistry 694 (2009) 4185–4195
The methyl singlet of the acetyl group in the 1H NMR spectrum
of 3b is downfield-shifted by 0.61 ppm compared to 2b as a conse-
quence of the acidic character (ꢀI-effect) of Nꢀ1 in the heteroaro-
matic pyrazole ring, while this N atom has a slightly basic nature in
the pyrazoline ring. The same reason explains the high frequency
of the amide-I band of 3b (1735 cmꢀ1, while this band is at
1649 cmꢀ1 in the IR spectrum of 2b.)
Table 1
Free energy-, entrophy- and ZPEa values of I–IV (Ar = Ph).b
G (au)
S (cal/molK)
G–G(III) (kJ/mol)
ZPE (kJ/mol)
I
II
III
IV
–2223.387466
–2223.371006
–2223.367793
–2223.392133
156.85
158.92
156.98
162.51
–63.89
–8.43
0
999.66
996.82
996.57
997.91
–76.14
The N-methyl 1H NMR signal of 3e and 5e is also significantly
downfield-shifted, which is characteristic of heteroaromatic sys-
tems [29a] relative to 2e (by 1.31 and 1.14 ppm) or 4e (by 1.40
and 1.23 ppm). The difference (upfield-shift in 4e and 5e by 0.09
and 0.17 ppm) between the regioisomeric pairs 2e–4e and 3e–5e
is due to the anisotropic shielding [29b] of the benzene ring in
pos. 5 in 4e and 5e.
a
Zero-point energy.
Calculated by B3LYP/6-31G(d,p).
b
formed as main product in 58% yield and the corresponding pyra-
zole (8a) was isolated as minor product in 6.3% yield. The 5-ferroce-
nyl-3-(p-hydroxyphenyl)-pyrazoline 7a, on standing at RT, slowly
decomposes, but in refrigerator in inert atmosphere it could be
stored for longer time. Acetylation of 7a with acetic anhydride in
pyridine at 0 °C led to the corresponding 5-ferrocenyl-3-(p-acet-
oxyphenyl)-pyrazoline (7b) as stable product in good yield. In a
similar way, reaction of 6 with p-nitrophenylhydrazine or with
2-hydrazinopyridine and subsequent acetylation of the crude prod-
ucts resulted in the corresponding stable 5-ferrocenyl-3-(p-acet-
oxyphenyl)-pyrazolines 9b and 10b. Pyrazoline 7b was converted
to the corresponding pyrazole 8b with 1.8 equiv. of DDQ, by reflux-
ing in benzene, in good yield (72%). The structures of all new com-
pounds were determined by NMR, IR, MS and in case of compounds
2d and 8a also by X-ray diffraction.
The C/Hꢀ20,50 and C/Hꢀ30,40 atom pairs give separated signals
for pyrazolines (except for 1H NMR signals of 2a,b because of acci-
dental isochrony [29c]) due to molecular asymmetry (Cꢀ5, for 11
also Cꢀ4 are chiral centra).
The Cꢀ10 chemical shift is significantly higher for pyrazolines
(86–91 ppm, while 75.4 0.2 ppm for pyrazoles) in accord with
the literature, because of the different a
-effects [29d,30] of sp3 and
sp2 carbon substituents [31]. The only irregular shift (78.3 ppm) of
4e is a further proof of the isomeric structure. In accord, the Cꢀ1 line
of the 5-phenyl group is also downfield-shifted as the consequence
of sp3-type carbon-substituent (141.5 ppm, while all other com-
pounds have line in the 122.4–134.2 ppm interval).
The structure of 11 was deduced from the following facts:
Apart from the signals of the phenyl, para-nitro-phenyl and
ferrocenyl substituents, three hydrogens are present in this mole-
cule one of which is a hydroxyl-H (as proved by the HMQC mea-
surement and the broad shape of its doublet signal in the 1H
NMR spectrum). The doublet split of this signal confirms the pres-
ence of a CHOH group in accordance with the downfield-position
of the C-line (69.7 ppm). Here, it is to be noted, that the assign-
ments of the pyrazoline C’s and H’s were proved by HMQC and
2.2. Structures and spectroscopy
2.2.1. NMR spectroscopy
The structures of the new compounds follow from the spectral
data (Tables 2–4) straightforwardly. Only a few additional remarks
are necessary:
Table 2
1H NMR dataa of compounds 2a–e, 3b–e, 4e, 5e, 7a,b, 8a,b, 9b, 10b and 11.b
CH2 (Pos. 4)d
H–5e
H–20,50
H–30,40
H–1–5
Cpf
H–2‘,6
H–3,5
H–4
H–2,6
H–3,5
H–4
OH
s (1H)
c
Compound
CH3
s (3H)
Pyrazoline ring
Substituted Cp ring
3/5-Phenyl/aryl groupg
N-aryl/
a
-pyridyl ringh
2a
2b
2c
2d
2e
3b
3c
3d
3e
4e
5e
7a
7b
8a
8b
9b
10b
11
–
2.19
–
3.05, 3.34
3.56, 3.82
3.78, 3.82
3.85, 4.04
3.15, 3.57
6.85
6.85
6.93
6.82
2.81, 3.34
6.53
5.85
5.37
5.06
5.49
3.91
–
–
–
–
3.94
–
4.67
4.39
4.15
4.21
4.18
4.17
4.24
4.22
4.16
4.12
4.18
4.19
4.17
4.05
4.22
4.23
4.13
4.09
4.12
4.15
4.17
7.67
7.87
7.86
7.94
7.68
7.90
7.95
7.93
7.80
7.47
7.56
7.70
7.88
7.71
7.92
7.83
7.89
8.02
ꢁ7.4i
ꢁ7.5i
7.47
7.53
7.39
7.47
7.45i
7.47
7.39
7.38
7.50
6.88
7.24
6.54
7.16
7.17
7.15
7.45
–
–
–
–
7.22
7.24
–
–
–
7.27
8.07
–
4.14
–
6.85
4.15i, 4.24
4.21, 4.58
4.25, 4.33
4.72
4.15i
7.39
7.49
7.33
7.41
7.36
7.39
7.28
7.30
7.44
–
–
–
–
–
–
7.50
–
–
–
–
–
–
–
–
–
9.80
–
9.53
–
–
–
3.91, 4.13
ꢁ4.19
4.36
2.67
2.80
–
–
–
7.42
–
–
–
–
6.70
6.73
7.49
–
–
4.22i
ꢁ7.45i
–
4.32
4.68
4.52, 4.55
4.65
4.28
4.40
4.33
4.25
7.56
–
–
8.21
–
–
–
7.17
7.18
7.52
3.98
2.58
3.81
–
2.30
–
2.32
2.22
2.22
–
–
3.68, 3.86
3.74, 3.92
7.01
5.13
5.23
–
3.96, 4.42
3.98, 4.44
4.27
4.10, 4.15
4.10, 4.15
4.20
7.09
7.13
7.41
ꢁ7.42i
7.16
7.20
7.19
6.79
–
4.21i
4.19i
3.57, 3.77
3.75, 3.96
5.86
5.52
5.40
4.95
3.91, 4.47
3.84, 4.49
3.87, 4.34
3.97, 4.02
4.03, 4.11
4.15, 4.25
7.46
7.98
8.12
6.61
–
–
–
2.44k
a
In CDCl3 (2a,c, 3b–d, 8b and 11) or DMSO-d6 (2b,d,e, 3e, 4e, 5e, 7a,b, 8a, 9b and 10b) solution at 500 MHz. Chemical shifts in ppm (dTMS = 0 ppm), coupling constants in
Hz.
b
Assignments were supported by HMQC (except for 3b,e) and for 2a,b and 7a also by COSY measurements.
Acetyl (b-type compounds) or N-methyl group (e-type compounds).
c
d
Two dd’s (2 ꢂ 1H), 2J: 17.9 0.1 (2b–d), 16.2 (2e, 4e), 17.3 (7a,b), 17.7 (9b), 3J (upfield dd): 4.0 0.2 (2b,d), 6.0 (2c), 13.6 (2e), 14.6 (4e), 5.2 (7a,b), 4.5 (9b), 3J (downfield
dd): 11.5 0.2 (2b–d, 7a,b, 9b), 9.8 (2e, 4e), coalesced to ꢁd and ꢁt (2a, 10b), ꢁd for 11, J: ꢁ8, s (1H) for pyrazoles (3b–e, 5e, 8a,b).
e
dd (1H), coalesced to ꢁd (10b), d, J: 1.5, (11).
f
Unsubstituted cyclopentadiene ring.
g
Pos. 5 for 4e and 5e.
h
H-3-5 signals (
Coalesced signals.
a-pyridyl, ꢁd, ꢁdt, ꢁt) for 9b, H–6: 8.05, ꢁd.
i
k
ꢁd, J: ꢁ8.

V. Zsoldos-Mády et al. / Journal of Organometallic Chemistry 694 (2009) 4185–4195
4189
Table 3
13C NMR chemical shifts (in ppm, dTMS = 0 ppm)a of compounds 2a–e, 3b–e, 4e, 5e, 7a,b, 8a,b, 9b, 10b and 11.b,c
d
Compound
CH3
C–3
C–4
C–5
C–10
C–20,50
C–30,40
C–1–5
C–1
C–2,6
C–3,5
C–4
C–1
C–3,5
C–3,5
C–4
Cpe
Pyrazoline ring
Substituted Cp ring
3-/5-Phenyl/aryl groupf
N-phenyl/
a
-pyridylg ring
2a
2b
2c
2d
2e
3b
3c
3d
3e
4e
5e
7a
7b
8a
8b
9b
10b
11k
–
22.6
–
151.7
155.4
147.8
154.1
149.8
153.4
152.1
153.4
149.4
150.9
149.3
149.1
147.8
151.6
151.3
150.6
153.4h
40.7
40.0
42.6
42.4
59.6
55.9
59.8
58.8
90.9
88.2
91.0
88.9
86.0
75.4
75.3
75.6
75.4
78.3
79.9
90.5
90.1
75.5
75.2
89.0
88.8
ꢁ85
66.4, 66.8
66.6, 70.9
68.5, 68.8
66.5, 70.1
66.8, 70.3
69.3
68.5, 68.7
68.5, 68.6
67.4, 68.1
68.6, 69.2
68.6, 69.0
69.13
68.9
69.4
69.1
69.6
69.4
70.3
70.3
70.5
70.2
69.96
70.1
69.5
69.5
70.5
70.3
69.4
69.7
69.2
133.4
132. 2
133.3
132.3
133.8
132.3
133.6
132.9
134.2
141.5
131.1
124.4
131.0
124.9
131.5
130.7
129.9
126.5
127.5
126.2
127.4
126.5
126.6
126.2
126.4
125.8
128.3
129.3
128.3
127.7
127.5
126.7
128.1
128.6
126.2
128.9
129.7
129.1
129.8
129.4
129.2
129.0i
129.2
129.4
129.4
129.7
116.5
123.1
116.2
122.1
123.1
123.3
129.6
129.1
131.1
129.0
130.8
129.2
129.5
128.3i
128.9
128.2
128.4
129.2
159.1
151.5
158.2
150.8
151.9
152.5h
130.4
–
–
–
–
–
–
–
–
145.8
149.3
–
114.6
113.2
–
129.2
126.5
–
119.7
138.5
–
–
41.5
24.6
–
40.4
68.9
109.6
104.2
107.4
103.4
45.0
104.4
42.5
42.2
104.1
104.1
40.4
42.4
83.4
146.8
143.5
143.7
142.8
73.5
144.5
59.2
59.7
143.4
143.6
57.7
58.9
67.9
–
–
–
–
69.05h
69.13h
140.5
145.4
–
–
–
145.9
145.4
141.1
140.8
156.1
149.2h
126.7
125.3
–
–
–
114.3
114.7
127.2
127.3
109.5
126.5
126.9
129.2i
124.6
–
128.5i
146.4
–
–
69.5
68.7
67.3, 67.6
67.1
70.1
69.7
70.0, 70.1
68.9
38.9
42.4
38.3
–
21.8
–
21.6
21.8
21.8
–
–
–
–
–
66.9, 70.1
66.9, 70.3
69.4
68.1, 68.7
68.1, 68.9
68.0
129.5
129.6
129.8
129.2
138.1
113.2
113.0
119.0
119.6
129.1
128.6
115.1
138.5
69.07h
69.11h
66.9, 71.3
66.5, 68.5
66.8, 68.5
68.4
69.2, 70.3
68.8, 69.0
a
b
c
d
e
f
In CDCl3 (2a,c, 3b–d, 8b and 11) or DMSO-d6 (2b,d,e, 3e, 4e, 5e, 7a,b, 8a, 9b and 10b) solution at 125 MHz.
Assignments were supported by DEPT (except for 3e and 11), HMQC (except for 3b,e) and HMBC (except for 2a,b, 9b and 10b) measurements.
Further signals: C@O: 170.9 (3b), 170.0 (7b, 9b and 10b), 169.8 (8b).
Acetyl (b-type compounds) or N-methyl group (e-type compounds).
Unsubstituted cyclopentadiene ring.
Pos. 5 for 4e and 5e.
g
h
i
a-Pyridyl (9b): C–2 - C–5, C–6: 148.1.
Interchangeable assignments.
Due to the low concentration of the measured solution the lines of quaternary carbons were not identifiable in the 13C NMR spectrum.
Table 4
Characteristic IR frequencies [cmꢀ1] of compounds 2a–e, 3b–e, 4e, 5e, 7a,b, 8a,b, 9b, 10b and 11 (in KBr discs).
Compound
m
C@O banda
masNO2 and
msNO2 band
mC–O band
c
CArH bandb
c
CArH bandb
c
CArCArbandc
masCp–Fe–Cp and tilt of Cp
2a
2b
2c
2d
2e
3b
3c
3d
3e
4e
5e
7a
7b
8a
8b
9b
10b
11
–
1649
–
–
–
1735
–
–
–
–
–
–
1761
–
1750
1751
1753
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
836
–
745
762
746, 758
763, 749
761
769
764
769
768
774
775
751
752
767
767
913d
–
695
691
707, 690
693
696
693
694
690
695
702
706
693
691
698
690
764d
–
508, 490
510, 487, 462
500, 484
487
490
502, 478
503
1595, 1318
–
–
–
–
1519, 1341
854
–
–
501
504
–
–
–
–
–
–
–
–
–
509, 486
509, 487
496
496, 479
505, 485
532, 503
512, 492
526, 490
489
–
833
845
836
851
855
840
834
1198, 1103
1263, 1236
1215, 1203, 1017
1195, 1008
1198, 1002
–
1507, 1495, 1305
–
–
Further bands:
mNH: 3308, sharp (2a), ꢁ3420, broad (7a), 3600–3000, diffuse (8a), ꢁ3400, broad (11).
a
Amide (2b, 3b) or ester group (7b, 8b, 9b, 10b).
Para-di- or mono-substituted benzene.
Mono-substituted benzene.
b
c
d
a-Pyridyl group.
HMBC measurements. e.g., The Cꢀ4 line (at 83.4 ppm) has long-
range coupling to the ortho-H’s of the phenyl group at 8.02 ppm.
The downfield-position of the latter signal is proof of the conjuga-
tion of the phenyl with the C@N double bond.
2.2.2. Electron impact mass spectrometry
The electron impact (EI) mass spectra of ferrocenyl pyrazolines
and ferrocenyl pyrazoles were also recorded. Among them we
comparatively studied regioisomeric pairs of some pyrazolines
(2e, 4e and 13a, 13b [7], see Schemes 1 and 3), as well as pyrazoles
(3e, 5e). For ferrocenyl–pyrazolines, including 2a–c, were previ-
ously published MS data [32], but to our knowledge, no reports
have appeared on ferrocenyl–pyrazoles.
Taking the coupling between Hꢀ4 and Hꢀ5 and the Cꢀ10 shift
of the substituted Cp ring (confirming sp3-type carbon-substitu-
tion) into consideration the structure of this intermediate is
unambiguous.
It is noteworthy that the quaternary carbon lines, due to very
low concentration of the solution of 11, were not identifiable, how-
ever, the HMBC cross peaks to Hꢀ4 and Hꢀ20,50 enable us to deter-
mine the approximately position of line Cꢀ10.
In the mass spectra of ferrocenyl pyrazolines the molecular ion
is present. These substances show medium fragmentation, mostly
dominated by fragments due to the ferrocene moiety. Although
there is no universal rule for any fragmentation pathways, a com-

4190
V. Zsoldos-Mády et al. / Journal of Organometallic Chemistry 694 (2009) 4185–4195
2.2.3. X-ray studies
X-ray crystal structure analysis of 2d and 8a revealed the struc-
tures depicted in Figs. 2 and 3, respectively. The selected bond
parameters are listed in Table 5.
N
N
N
N
N
In both crystal structures the two cyclopentadienyl rings (C1–
C2–C3–C4–C5 and C6–C7–C8–C9–C10) of the ferrocene moiety
are parallel, the plane angle between them is 4.4(3)° in 2d and
1.0(9)° in 8a. The conformation of the ferrocene in both molecules
is eclipsed.
Fe
Fe
N
13a
13b
The molecules of 2d have chirality, but in the crystal there was a
racemate. The conformation of N1 atom is nearly planar, as it also
can be seen from the NMR shifts and from the sum of angles
(356.9°). And because of this nitrogen atom planarity the pyrazo-
line ring is almost planar, it has only a little envelope structure
with the C11 atom on the tip (0.125 Å above the plane of the other
four atoms of the ring). The angle between the least-squares planes
of the pyrazoline and the p-nitrophenyl rings is 16.8(4)°, and be-
tween pyrazoline and phenyl rings is 12.9(4)°.
Scheme 3.
mon spectral feature is the presence of a peak at 186 amu, which
can be assigned to the ferrocene ion (FcH+). This peak is absent
in the spectra of ferrocenyl–pyrazoles. The [M–2]+ ion can be found
and in most cases is more intensive than that according to the 54Fe
isotope containing ion. The hydrogen molecule loss is rather unu-
sual in EI MS. To clarify this point, energy dependent measure-
ments were performed for compound 2c. Varying the electron
energy from 6 to 75 eV there is a strong dependence of the inten-
sity of the [M–2]+ ions peak on electron energy: at the lowest ener-
gies no fragmentation occurs, i.e. the [M–2]+ peak is absent, then
the intensity rises to a maximum after which it tends to a lower
constant value, as other fragmentation pathways start up. Fig. 1
shows the energy dependence of some common peaks of ferroce-
nyl–pyrazolines.
An important question related to the studied molecules is the
possibility to discriminate 5-ferrocenyl and 3-ferrocenyl com-
pounds. The appearance of the ions at 212 (FcC2H3+) or 211
(FcCN+) amu is a good method to distinguish these compounds.
+
FcC2H3 appears in case of 5-ferrocenyl-pyrazolines, whereas
FcCN+ is typical for 3-ferrocenyl compounds. Information about
Nꢀ1 substitutent of the ring is given by the loss of the R0NH moi-
ety, which usually occurs from the molecular ion.
Ferrocenyl pyrazoles show low degree of fragmentation. As
mentioned before, the ferrocene ion is not present. In the case of
pyrazoles it is hard to differentiate between 5-ferrocenyl and 3-
ferrocenyl compounds. One difference between them is that 3-ferr-
ocenyl-pyrazoles have higher degree of fragmentation than the iso-
mer 5-ferrocenyl ones. Another way to distinguish these
compounds is the appearance of the FcC2H+ ion at 210 amu in case
of 5-ferrocenyl-pyrazoles, but usually it is of low intensity.
Fig. 2. The ortep drawing of compound 2d (the ellipsoid probability is 30%). Only
non-hydrogen atoms are labelled.
N
Fc
N
0.2
0.0
30
60
Electron energy / eV
Fig. 1. Energy dependence of the intensity of some peaks of 2c (4 – M+, s – [M–2]+,
h – FcC2H3+, 5 – FcH+, } – CpFe+).
Fig. 3. The ortep drawing of compound 8a (the ellipsoid probability is 30%). Only
non-hydrogen atoms are labelled.

V. Zsoldos-Mády et al. / Journal of Organometallic Chemistry 694 (2009) 4185–4195
4191
Table 5
Selected bond lengths, angles and torsion angles for 2d and 8a.
2d
8a
2d
8a
Bond lengths [Å]
O(1)–C(17)
C(23)–N(3)
N(1)–C(13)
N(1)–N(2)
N(2)–C(11)
Compound
1.370(15)
Bond lengths [Å]
N(2)–C(20)
C(10)–C(11)
C(13)–C(14)
C(12)–C(13)
C(11)–C(12)
Compound
1.367(7)
1.497(8)
1.438(8)
1.483(8)
1.548(8)
2d
1.413(16)
1.475(16)
1.474(16)
1.396(16)
1.376(17)
8a
1.480(8)
1.303(6)
1.392(6)
1.504(7)
2d
1.331(15)
1.368(13)
1.374(14)
8a
Angles [°]
C(13)ꢀN(1)ꢀN(2)
N(1)ꢀN(2)ꢀC(11)
N(1)ꢀC(13)ꢀC(12)
N(1)ꢀC(13)ꢀC(14)
C(12)ꢀC(13)ꢀC(14)
C(11)ꢀC(12)ꢀC(13)
N(2)ꢀC(11)ꢀC(12)
N(2)ꢀC(11)ꢀC(10)
C(12)ꢀC(11)ꢀC(10)
109.0(5)
113.0(4)
112.6(6)
121.8(6)
125.6(5)
105.4(5)
99.3(5)
105.5(10)
110.8(10)
111.2(11)
120.7(11)
128.0(12)
105.9(12)
106.5(11)
123.4(12)
129.8(11)
Torsion angles [°]
C(13)ꢀN(1)ꢀN(2)ꢀC(11)
C(13)ꢀN(1)ꢀN(2)ꢀC(20)
N(2)ꢀN(1)ꢀC(13)ꢀC(12)
N(2)ꢀN(1)ꢀC(13)ꢀC(14)
C(15)ꢀC(14)ꢀC(13)ꢀN(1)
C(19)ꢀC(14)ꢀC(13)ꢀN(1)
N(1)ꢀN(2)ꢀC(20)ꢀC(25)
N(1)ꢀN(2)ꢀC(20)ꢀC(21)
C(22)ꢀC(23)ꢀN(3)ꢀO(1)
2.5(6)
163.9(5)
3.2(7)
ꢀ178.3(5)
ꢀ168.0(6)
15.4(9)
ꢀ1.4(14)
ꢀ178.5(11)
0.8(14)
ꢀ176.6(11)
ꢀ144.3(13)
37.5(18)
15.5(8)
ꢀ59.8(17)
110.8(5)
115.6(5)
ꢀ162.7(5)
120.9(13)
ꢀ0.8(9)
In 8a the aromatic character of the pyrazole moiety can be seen
from the planarity of the ring and from the bond distances in it (see
Table 5.). The extended conjugation including the cyclopentadi-
enyl, pyrazole and the two phenyl moieties cannot realize because
of sterical effects. The angle between the least-squares planes of
the central pyrazole and the 4-hydroxy-phenyl rings is 37.4(6)°,
and between the pyrazole and the phenyl rings is 57.8(6)°. In the
crystals of 8a the planar chirality appears, because of this the space
group is acentric (P212121).
6 to 75 eV. In the case of compounds 2e, 4e and 8b the fragment
compositions were confirmed by accurate mass measurements.
The X-ray measurements were made on a Rigaku AFC6S diffrac-
tometer with graphite monochromated Cu
K
a
radiation
(k = 1.54178 Å). Cell constants and an orientation matrix for data
collection were obtained from a least-squares refinement using
the setting angles of carefully centred reflections. The crystals of
2d and 8a were mounted on a glass fibre. The data were collected
at a temperature of 293 K using the
x/2h scan technique. Crystal
The main crystal building forces are the dispersion interactions
between the ferrocene and phenyl moieties, and the hydrogen
bonds. In the crystal of 2d the hydrogen bonded molecules (be-
tween C19–H19 and O2 [2 – x, 1 ꢀ y, 1 ꢀ z] atoms) form dimers,
while in the crystal of 8a (hydrogen bond between the O1–H1A
and N1 [ꢀx + 1.5, ꢀy + 2, z ꢀ 0.5] atoms) these molecules form H-
bonded chain. The parameters of the hydrogen bonds are summa-
rized in Table 6. In both cases there are distinct layers of the apolar
ferrocenes and the other three rings of the molecules, but in 2d
perpendicular, in 8a parallel to the ac plane of the unit cell.
data for 2d: C25H21FeN3O2, Fwt: 451.3, yellow plate, size:
0.5 ꢂ 0.3 ꢂ 0.1 mm, monoclinic, space group P21/n (No. 14),
a = 17.347(2) Å, b = 6.000(4) Å, c = 19.524(2) Å, b = 94.98(1)°,
V = 2024(1) Å3, Z = 4, DC = 1.481 Mg/m3, 3628 reflections, 3503 un-
ique and 1344 > 2r(I). Crystal data for 8a: C25H20FeN2O, Fwt:
420.2, orange plate, size: 0.75 ꢂ 0.25 ꢂ 0.07 mm, orthorombic,
space group P212121 (No. 19), a = 13.04(2) Å, b = 25.17(2) Å,
c = 5.94(2) Å, V = 1949(6) Å3, Z = 4, DC = 1.432 Mg/m3, 3818 reflec-
tions, 3221 unique and 1195 > 2
out by use of the software supplied with the diffractometer. The
linear absorption coefficient, for Cu radiation is
r(I). Data processing was carried
l
,
Ka
6.202 mmꢀ1 for 2d and 6.345 mmꢀ1 for 8a. An empirical absorp-
tion correction based on azimuthal scans of several reflections
was applied. Structure solutions with direct methods were carried
out with the teXsan Crystal Structure Analysis Package [33].
Refinements were carried out using the SHELXL-97 [34] program
by the full matrix, least-squares method on F2. All non-hydrogen
atoms were refined anisotropically. Hydrogen atoms were gener-
ated based upon geometric evidence and their positions were re-
fined by the riding model. The final R1 = 0.0545 and wR2 = 0.1238
3. Experimental
General: IR spectra were recorded with a Bruker IFS-55 FT-spec-
trometer using KBr pellets. The 1H and 13C NMR spectra were ob-
tained at 500 and 126 MHz by a Bruker DRX-500 spectrometer in
CDCl3 or DMSO-d6 solution, with the deuterium signal of the sol-
vent as the lock and Me4Si as internal standard. The standard Bru-
ker micro program NOEMULT.AU to generate NOE was used with a
selective pre-irradiation time. DEPT spectra were run in a standard
for 3503 > 2
ness-of-fit = 0.91 for 2d. The final R1 = 0.0810 and wR2 = 0.1874 for
1195 > 2 (I) intensity data, number of parameters = 263, good-
ness-of-fit = 0.93, absolute structure parameter Flack
x = 0.021(17) [35] for 8a.
r(I) intensity data, number of parameters = 281, good-
manner, using only the
H = 135° pulse to separate CH/CH3 and CH2
r
lines phased ‘‘up” and ‘‘down”, respectively. The 2D-HMQC spectra
were obtained by using the standard Bruker pulse program
HXCO.AU.
Electron impact mass spectra (70 eV) were recorded on a Kratos
MS-80 and a Fisons TRIO 1000 mass spectrometer using direct
evaporation. The source temperature was between 200 and
230 °C. During the energy dependent measurement the source
temperature was kept at 80 °C and the electron energy varied from
TLC was performed on aluminium plates precoated with Silica
gel 60 F254 (E. Merck) and were developed with solvent or solvent
mixtures: A, CH2Cl2; B, 7:3 n-hexane–EtOAc; C, 95:5 CH2Cl2–EtOAc;
D, 4:1 CH2Cl2–EtOAc, the spots were detected visually or by UV
light at 254 nm and 366 nm, respectively. Column chromatography
was made on Silica gel (E. Merck, 0.020–0.043 mesh). M.p. data
were measured in capillary tubes and are not corrected.
Syntheses: Formylferrocene, p-hydroxyacetophenone, phen-
ylhydrazine, methylhydrazine, p-nitrophenylhydrazine, 2-hydrazi-
nopyridine, N-bromo-succinimide and DDQ were purchased from
Sigma–Aldrich. Procedures for the preparation of 3-ferrocenyl-1-
aryl-prop-2-en-1-ones 1 [7,36] and 6 [14], respectively, were de-
scribed earlier. Compounds 2a–c were prepared by modification
of known procedures [18].
Table 6
Hydrogenꢀbonds in 2d and 8a.
Donor–Hꢃ ꢃ ꢃAcceptor
C19ꢀH19ꢃ ꢃ ꢃO2 (a) in 2d
O1ꢀH1Aꢃ ꢃ ꢃ N1 (b) in 8a
d (D–H)
d (Hꢃ ꢃ ꢃA)
2.60
2.09
d (Dꢃ ꢃ ꢃA)
3.232(8)
2.898
<(D–Hꢃ ꢃ ꢃA)
125.4
167.2
0.93
0.82
Symmetry transformations: (a) ꢀx + 2, ꢀy + 1, ꢀz + 2; (b) ꢀx + 1.5, ꢀy + 2, z ꢀ 0.5.

4192
V. Zsoldos-Mády et al. / Journal of Organometallic Chemistry 694 (2009) 4185–4195
3.1. 5-Ferrocenyl-3-phenyl-4,5-dihydro-1H-pyrazole (2a)
C25H21FeN3O2 (451.31): C, 66.53; H, 4.69; N, 9.31. Found: C, 66.35;
H, 4.81; N, 9.43%. MS: 451(91) M+, 449(23) [M–H2]+, 419(55),
314(29) [M–R0NH]+, 248(23) [M–C5H5–R0N]+, 212(100) [FcC2H3]+,
210(26) [FcC2H]+, 186(73) [FcH]+, 121(93) [CpFe]+.
To a stirred suspension of 1 (1.22 g, 3.86 mmol) was added
dropwise 55% aqueous solution of hydrazine hydrate (16 mL) and
the mixture was refluxed for 2.5 h, filtered and cooled. The sepa-
rated pale yellow crystals of 2a were filtered and washed with cold
ethanol. Yield 1.15 g (90%), m.p. 105–107 °C (decomp.). In our
experience, compound 2a can be stored without decomposition
for years in refrigerator. MS: 330 (100) [M+], 328(19) [M–2]+,
314(6) [M–R0NH]+, 265(4) [M–C5H5]+, 263(5) [M–2–C5H5]+, 227
(12) [M–RPhCN]+, 212(34) [FcC2H3]+, 186(51) [FcH]+, 121(49)
[CpFe]+, 56(25) [Fe]+.
From the reaction a less moving component was also isolated
by chromatography and was crystallized from petroleum ether to
give brown crystals (11, 31 mg, 1.4%), m.p. 186–188 °C; Rf 0.24
(solvent A). MS (C25H21FeN3O3): 467 (M+), 449 (M–H2O). The pyra-
zole compound 3d was also detected in the mother liquor.
3.5. 1-Acetyl-5-ferrocenyl-3-phenyl-1H-pyrazole (3b)
To a solution of 1-acetyl-5-ferrocenyl-3-phenyl-4,5-dihydro-
1H-pyrazole (2b, 300 mg, 0.81 mmol) in benzene (20 mL) was
dropped a solution of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone
(DDQ, 100 mg) in benzene (8.5 mL) and the reaction mixture was
heated to reflux temperature. After 1 h, an identical portion of
DDQ solution was added and 1 h later further 35 mg DDQ in
3 mL benzene (total amount of DDQ 235 mg, 1.03 mmol, in
20 mL benzene, total reflux time 4 h), than the mixture was cooled
to RT. It was filtered through Silica gel, washed with dichlorometh-
ane and the crude product was purified by repeated column chro-
matography using dichloromethane and then dichloromethane–
3.2. 1-Acetyl-5-ferrocenyl-3-phenyl-4,5-dihydro-1H-pyrazole (2b)
3.2.1. Procedure A
To a cooled solution of acetic anhydride (0.8 mL) in dry pyridine
(1 mL) was added compound 2a (0.109 g, 0.33 mmol) and the mix-
ture was stirred at 0 °C for 5 h, and then it was allowed to stand in
refrigerator for 24 h. The solution was poured into ice–water and
the solidified crude product (0.112 g, 91.1%) was purified by col-
umn chromatography using dichloromethane as eluent. Crystalli-
zation from ethanol gave yellow crystals of pure 2b (0.094 g,
76.5%), m.p. 184–185 °C, Rf 0.24 (solvent A), lit. m.p. 180–181 °C
[18b]. For an alternative recent preparation and X-ray data of 2b
see [12b] with lit. m.p. 184–185 °C. MS: 372(100) [M+], 370(8)
[M–H2]+, 307(58) [M–C5H5]+, 288(1) [M–42]+, 287(8) [M–43]+,
269(26) [M–RPhCN]+, 212(4) [FcC2H3]+, 186 (5) [FcH]+, 121(23)
[CpFe]+, 56(15) [Fe]+.
ethyl-acetate 9:1 as eluent. Although
a significant amount
(130 mg) of the starting material 2b was recovered, longer reaction
time or reflux in toluene instead of benzene did not give better re-
sults. Product 3b was crystallized from petroleum ether to give
dark-orange rhomboid crystals (70 mg, reduced yield 42%), m.p.
133–134 °C; Rf 0.83 (solvent A). Anal. Calc. for C21H18FeN2O
(370.23): C, 68.13; H, 4.90; N, 7.57. Found: C, 67.98; H, 4.99; N,
7.46%. MS: 370(65) M+, 328(100) [M–42]+, 263(10) [M–42–
C5H5]+, 207(4) [M–42–FeCp]+, 121(35) [CpFe]+, 56(14) [Fe]+,
43(97) [Ac+].
3.2.2. Procedure B
Realizing the reaction in larger scale, in some cases crystals of
2b were spontaneously separated from the reaction mixture. After
filtration and washing with cold ethanol–water (7:3), pure product
was obtained in ꢁ55% yield. The mother liquor of the reaction was
worked up, as described in Section 3.2.1, resulting in further crop
of 2b, total yield 75%.
3.6. 5-Ferrocenyl-1,3-diphenyl-1H-pyrazole (3c)
3.6.1. Method A: dehydroaromatisation with DDQ
To a stirred solution of 5-ferrocenyl-1,3-diphenyl-4,5-dihydro-
1H-pyrazole (2c, 0,15 g, 0,37 mmol) in dichloromethane (6 mL)
was added a solution of DDQ (0,11 g, 0,48 mmol) in dichlorometh-
ane (10 mL). In a few minutes dark greyish-green precipitate (qui-
none–hydroquinone complex) separated from the homogeneous
reaction mixture. After 1 h stirring TLC (solvent A) indicated com-
plete reaction. The solid was filtered and washed several times
with dichloromethane. The filtrate was evaporated and purified
by column chromatography using benzene as eluent. After evapo-
ration pure 3c (139 mg, 79%) was obtained as pale yellow syrup,
which slowly crystallized from methanol, m.p. 100–101 °C; Rf
0.69 (solvent A). Anal. Calc. for C25H20FeN2 (404.29): C, 74.27; H,
4.99; N, 6.93. Found: C, 74.72; H, 5.08; N, 6.96%. MS: 404(14) M+,
339(9) [M–C5H5]+, 121(4) [CpFe]+, 56(6) [Fe]+, 210(10) [FcC2H]+,
374 (100) [M–30]+.
3.3. 5-Ferrocenyl-1,3-diphenyl-4,5-dihydro-1H-pyrazole (2c)
3-Ferrocenyl-1-phenyl-prop-2-en-1-one (1, 1.51 g, 4.77 mmol)
and phenylhydrazine (1.75 g, 16.2 mmol) was added to a mixture
of abs. ethanol (22 mL), dist. acetic acid (15 mL) and water (5 mL)
and the reaction was boiled for 4 h under argon, by protecting from
light. The separated yellow product was washed with cold etha-
nol–water and recrystallized from ethanol–water, to give pure 2c
as yellow needles (1.47 g, 76%), m.p. 158–159 °C; Rf 0.92 (solvent
A). Anal. Calc. for C25H22FeN2 (406.31): C, 73.90; H, 5.46; N, 6.89.
Found: C, 73.45; H, 5.79; N, 6.73%. MS: 406(100) [M+], 404(39)
[M–H2]+, 376(2) [M–30]+, 374(8) [M–30–2]+, 341(4) [M–C5H5]+,
339(6) [M–H2–C5H5]+, 314(26) [M–R0NH]+, 285(3) [M–FeCp]+,
283(2) [M–H2–FeCp]+, 249(28) [M–C5H5–R0N]+, 212(86) [FcC2H3]+,
186(53) [FcH]+, 121(97) [CpFe]+, 56(29) [Fe]+.
3.6.2. Method B: dehydroaromatisation with Cu(II)-nitrate and
sonication
3.4. 5-Ferrocenyl-1-(4-nitrophenyl)-3-phenyl-4,5-dihydro-1H-
pyrazole (2d)
To a solution of pyrazoline 2c (0.30 g; 0.74 mmol) in dichloro-
methane (10 mL) was added Cu(NO3)2ꢃ3H2O (0.36 g, 1.48 mmol)
and the reaction mixture was sonicated at RT and monitored by
TLC (solvent A). After 2 h further amounts of Cu(NO3)2ꢃ3H2O
(0.18 g, 0.74 mmol) and dichloromethane (8 mL) were added and
sonication was continued for 2 h, then the mixture was allowed
to stand at RT for 14 h. Addition of newer portion of the reagent
(0.74 mmol), sonication for further 2 h and standing at RT for
14 h resulted in complete reaction. The mixture was filtered,
washed with dichloromethane, evaporated and purified by column
chromatography using dichloromethane as eluent. Repeated
3-Ferrocenyl-1-phenyl-prop-2-en-1-one (1, 1.00 g, 3.16 mmol)
and 4-nitrophenylhydrazine was boiled in a mixture of ethanol
(15 mL), distilled acetic acid (22 mL) and water (3 mL) for 3 h un-
der argon, while TLC (solvent A) indicated complete reaction. After
cooling dark yellow crystals separated, which were filtered and
washed with cold ethanol–water to give pure 2d (1.045 g, 73%).
From the mother liquor further crop of 2d was isolated and puri-
fied by column chromatography using dichloromethane as eluent,
total yield 81%; m.p. 225–226 °C; Rf 0.85 (solvent A). Anal. Calc. for

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4193
chromatography with toluene resulted in pure product as pale yel-
low syrup, which on trituration with cold methanol gave crystal-
line 3c (0.11 g, 37%), m.p. 100–101 °C, identical with the product
described in Section 3.6.1.
tals of the regioisomeric pyrazoline (4e, 0.021 g, 1.3%), m.p. 126–
127 °C; Rf 0.81 (solvent B). Anal. Calcd for C20H20FeN2 (344.24): C,
69.78; H, 5.86; N, 8.14. Found: C, 69.89; H, 5.63; N, 8.18%. MS:
344(41) M+, 342(50) [M–H2]+, 277(8) [M–H2–C5H5]+, 267(100)
[M–RC6H4]+, 221(3) [M–H2–FeCp]+, 211(6) [FcCN]+, 210(2)
[FcC2H]+, 186(6) [FcH]+, 121(26) [CpFe]+, 56(13) [Fe]+.
The third component was crystallized from n-hexane to give 3e
pyrazole (0.07 g, 4%), yellow crystals, m.p. 90–91 °C; Rf 0.71 (sol-
vent B). Anal. Calcd. for C20H18FeN2 (342.22): C, 70.19; H, 5.30; N,
8.19. Found: C, 69.92; H, 5.42; N, 8.12%. MS: 342(100) M+, 277(3)
[M–C5H5]+, 221(3) [M–FeCp]+, 210(4) [FcC2H]+, 121(31) [CpFe]+,
56(15) [Fe]+.
The most slowly moving main product was crystallized from n-
hexane (or from ethyl-acetate) resulting in orange crystals of the
regioisomeric pyrazole (5e, 0.70 g, 43%), m.p. 139–140 °C; Rf 0.57
(solvent B). Anal. Calcd. for C20H18FeN2 (342.22): C, 70.19; H,
5.30; N, 8.19. Found: C, 70.01; H, 5.39; N, 8.03%. MS: 342(100)
M+, 277(5) [M–C5H5]+, 221(12) [M–FeCp]+, 121(38) [CpFe]+,
56(10) [Fe]+.
The N-methyl-pyrazolines (2e and 4e) during chromatography,
or standing in solution even at RT, spontaneously were partly
transformed to the corresponding pyrazoles 3e and 5e, respec-
tively, and reconversion of chalcone 1 was also observed at purifi-
cation of the yellow crude product mixture. A further by-product
was isolated in traces during chromatography and was supposed
to be 5-ferrocenyl-3-phenyl-1-H-pyrazole (see at 3e, but R = H,
R0 = H), on the basis of the MS spectrum, m/z = 328 (M+).
3.6.3. Method C: dehydroaromatisation with N-bromo-succinimide
To a suspension of pyrazoline 2c (0.30 g; 0.74 mmol) in anhy-
drous carbon tetrachloride (15 mL) was added N-bromo-succini-
mide (NBS, 0.15 g, 0.84 mmol) and three drops of dry pyridine
and the mixture was refluxed under nitrogen and was monitored
by TLC (solvent A). After 4 h further amounts of NBS
(0.075 g;0.42 mmol), CCl4 (5 mL) and two drops of dry pyridine
were added and after 10 h boiling, repeated addition of the same
amount of reagents was carried out and boiling was continued
for further 10 h. The hot solution was decanted from the separated
dark-brown oil and extracted with hot carbon tetrachloride
(2 ꢂ 8 mL). The united solutions were evaporated and the crude
oily product was purified by column chromatography (toluene)
to give pure 3c (0.086 g, 29%), identical with the product described
in Section 3.6.1.
3.7. 5-Ferrocenyl-1-(4-nitrophenyl)-3-phenyl-1H-pyrazole (3d)
To the stirred solution of 2d (40 mg; 0.088 mmol) in toluene
(20 mL) was added dropwise
a solution of DDQ (24 mg;
0.106 mmol) in toluene (12 mL) and the mixture was heated on a
bath at 120 °C for 3 h and then further heated at 100 °C for 3 h,
by that time greyish-green precipitate was separated from the
homogeneous reaction mixture and TLC (solvent A) indicated com-
plete reaction. The solid was filtered and washed several times
with dichloromethane. The filtrate was evaporated and purified
by column chromatography using dichloromethane as eluent and
was crystallized by treating petroleum ether to give pure 3d
(30 mg, 76%) in the form of orange crystals, m.p. 183–184 °C, Rf
0.74 (solvent A). Anal. Calc. for C25H19FeN3O2 (449.29): C, 66.83;
H, 4.26; N, 9.35. Found: C, 66.52; H, 4.37; N, 9.56%. MS: 449(14)
M+, 419 (100) [M–30]+, 384(10) [M–C5H5]+, 298(3) [M–30–FeCp]+,
210(10) [FcC2H]+, 121(4) [CpFe]+, 56(9) [Fe]+.
3.8.2. Method B
To the boiling solution of 1 (0.25 g, 0.79 mmol) in toluene
(8 mL) was added
a solution of methylhydrazine (0.10 g,
2.17 mmol) in toluene (2 mL) and the reaction mixture was re-
fluxed under nitrogen. After 1 h, methylhydrazine (0.10) was
added again to the hot solution and refluxing was continued for
further 1.5 h. TLC (solvent B) revealed the formation of a mixture
with the predominance of 4e and 5e. Repeated chromatography
(n-hexane–ethyl-acetate 7:3) under nitrogen resulted in 4e pyraz-
oline as orange crystals from petroleum ether (0.021 g, 8%) and 5e
as dark-orange crystals (0.158 g, 58%) from hexane, identical with
the corresponding products described in Section 3.8.1. A significant
transformation of 4e–5e was observed during chromatography.
Pyrazoline 2e (29.7 mg, 11%) and pyrazole 3e (8.1 mg, 3%), respec-
tively, were also isolated from the mixture.
Dehydroaromatisation with N-bromo-succinimide: Reaction of 2d
with NBS in carbon tetrachloride, as described at the preparation of
3c (Method C), after chromatography (dichloromethane) and crys-
tallization resulted in 3d in 8% yield.
3.8. Reaction of 3-ferrocenyl-1-phenyl-prop-2-en-1-one (1) with
methylhydrazine; preparation of 5-ferrocenyl-3-phenyl-1-methyl-4,5-
dihydro-1H-pyrazole (2e); 5-ferrocenyl-3-phenyl-1-methyl-1H-pyra-
zole (3e); 3-ferrocenyl-5-phenyl-1-methyl-4,5-dihydro-1H-pyrazole
(4e) and 3-ferrocenyl-5-phenyl-1-methyl-1H-pyrazole (5e)
3.9. Reaction of 1-ferrocenyl-3-(p-hydroxyphenyl)-prop-2-en-1-one
(6) with phenylhydrazine; preparation of 5-ferrocenyl-3-(4-hydroxy-
phenyl)-1-phenyl-4,5-dihydro-1H-pyrazole (7a) and 5-ferrocenyl-3-
(4-hydroxyphenyl)-1-phenyl-1H-pyrazole (8a)
3.8.1. Method A
To a solution of compound 6 (0.35 g, 1.05 mmol) in a mixture of
ethanol (10 mL), acetic acid (3.75 mL) and water (3.75 mL) was
added phenylhydrazine and the reaction mixture was heated un-
der reflux in nitrogen atmosphere for 3 h, by which time the colour
of the solution became yellow and TLC (solvent B) indicated com-
plete reaction. After standing in refrigerator for 5 h, the mixture
was evaporated to give a dark-brown syrup. It was dissolved in
ethyl-acetate and extracted with water. The organic phase was
dried and evaporated to give oily-solid crude product, which was
purified by repeated column chromatography using n-hexane–
ethyl-acetate (7:3 ? 1:9) as eluent. The faster moving yellow prod-
uct was crystallized from ethyl-acetate–n-hexane (7a, 0.26 g, 58%)
m.p. 110–111 °C; Rf 0.71 (solvent C). Anal. Calcd. for C25H22FeN2O
(422.31): C, 71.10; H, 5.25; N, 6.63. Found: C, 70.87; H, 5.44; N,
6.26%. MS: 422(69) M+, 420(82) [M–H2]+, 357(3) [M–C5H5]+,
355(8) [M–H2–C5H5]+, 330(19) [M–R0NH]+, 303(5) [M–RPhCN]+,
301(8) [M–FeCp]+, 299(4) [M–H2–FeCp]+, 266(20) [M–C5H5–R0N]+,
To a solution of chalcone 1 (1.50 g, 4.74 mmol) in ethanol
(40 mL) was added methylhydrazine (1.418 g, 30.8 mmol) and
the mixture was heated under reflux for 1 h, by that time TLC (sol-
vent B) indicated complete conversion. Formation of four main
products and several by-products was observed. Separation of
the components was made by repeated column chromatography
(n-hexane–ethyl-acetate 3:1) under nitrogen. The fast moving
product was crystallized from ethyl-acetate to give pure pyrazoline
(2e, 0.37 g, 23%), in the form of yellow crystals, m.p. 114–115 °C; Rf
0.86 (solvent B). Anal. Calcd for C20H20FeN2 (344.24): C, 69.78; H,
5.86; N, 8.14. Found: C, 69.29; H, 5.83; N, 8.22%. MS: 344(76) M+,
342(20) [M–H2]+, 314(5) [M–R0NH]+, 277(3) [M–H2–C5H5]+,
249(5) [M–C5H5–R0N]+, 212(33) [FcC2H3]+, 186(100) [FcH]+,
121(72) [CpFe]+, 56(16) [Fe]+.
The second moving material after separation and crystallization
from ethyl-acetate–petroleum ether gave yellowish-orange crys-

4194
V. Zsoldos-Mády et al. / Journal of Organometallic Chemistry 694 (2009) 4185–4195
212(69) [FcC2H3]+, 210(31) [FcC2H]+, 186(79) [FcH]+, 121(100)
[CpFe]+, 56(38) [Fe]+.
C, 66.83; H, 5.16; N, 9.29%. MS: 465(10) M+, 463(2) [M–H2]+, 400(3)
[M–C5H5]+, 304(25) [M–RPhCN]+, 212(16) [FcC2H3]+, 210(5)
[FcC2H]+, 186(3) [FcH]+, 121(48) [CpFe]+, 56(17) [Fe]+, 43(100) Ac+.
The second moving product gave orange crystals (8a, 0.028 g,
6.3%) from n-hexane, m.p. 225–226 °C; Rf 0.28 (solvent C). Anal.
Calcd for C25H20FeN2O (420.29): C, 71.44; H, 4.80; N, 6.67. Found:
C, 71.15; H, 5.02; N, 6.45%. MS: 420(100) M+, 355(6) [M–C5H5]+,
299(3) [M–FeCp]+, 210(39) [FcC2H]+, 186(11) [M–C5H5–R0N]+,
121(31) [CpFe]+, 56(14) [Fe]+.
3.13. 3.3.6. 3-(4-Acetoxyphenyl)-5-ferrocenyl-1-(4-nitrophenyl)-4,5-
dihydro-1H-pyrazole (10b)
Compound 6 (0.50 g, 1.5 mmol) was dissolved in a mixture of
ethanol (9 mL), acetic acid (3 mL) and water (0.75 mL), p-nitro-
phenylhydrazine (0.482 g, 3.15 mmol) was added and the suspen-
sion was refluxed under nitrogen for 6 h and then it was allowed to
stand at RT for 20 h. On the basis of TLC analysis (solvent D), fur-
ther amount of p-nitrophenylhydrazine (0.06 g, 0.39 mmol), etha-
nol (3 mL), acetic acid (1.5 mL) and water (1.0 mL) was added to
the mixture and heating was continued for further 7 h. On cooling
orange crystals separated, which were filtered and washed with
cold methanol–water (1:1) to give 0.57 g (81%) 3-(p-hydroxy-
phenyl)-5-ferrocenyl-pyrazoline derivative (14, see at 10b, but
R = p-OH, R0 = p-NO2Ph). Crude 14 was acetylated with acetic anhy-
dride (2 mL) and pyridine (3.25 mL) by stirring for 4 h at RT and
then storing the reaction mixture at 0 °C for 20 h. The separated
red crystals were filtered, washed with methanol–water (1:1)
and recrystallized from ethyl-acetate–n-hexane to give pure 10b
(0.388 g, 51%, yield calculated for chalcone 6), m.p. 236–237 °C;
Rf 0.57 (solvent A). Anal. Calc. for C27H23FeN3O4 (509.34): C,
63.67; H, 4.55; N, 8.25. Found: C, 63.96; H, 4.46; N, 8.49%. MS:
509(6) M+, 479(15) [M–30]+, 477(5) [M–30–2]+, 330(9) [M–42–
R0NH]+, 212(23) [FcC2H3]+, 210(4) [FcC2H]+, 186(18) [FcH]+,
121(43) [CpFe]+, 56(17) [Fe]+, 43(100) Ac+.
3.10. 3-(4-Acetoxyphenyl)-5-ferrocenyl-1-phenyl-4,5-dihydro-1H-
pyrazole (7b)
Compound 7a (0.300 g, 0.71 mmol) was acetylated with dist.
acetic anhydride (1 mL) in dry pyridine (1.7 mL) for 48 h at 0 °C
and then at RT for 2 h, by which time TLC (solvent A) indicated
complete reaction. The mixture was poured into ice–water and
the solidified material was filtered and washed several times with
cold water to give 0.30 g crude product. Purification by column
chromatography (dichloromethane) resulted in yellow crystals of
7b (0.226 g, 68.5%), m.p. 193–194 °C; Rf 0.74 (solvent A). Anal. Calc.
for C27H24FeN2O2 (464.35): C, 69.84; H, 5.21; N, 6.03. Found: C,
69.98; H, 5.47; N, 6.18%. MS: 464(72) M+, 462(21) [M–H2]+,
422(7) [M–42]+, 420(9) [M–42–H2]+, 330(34) [M–42–R0NH]+,
212(85) [FcC2H3]+, 186(97) [FcH]+, 121(100) [CpFe]+, 56(24) [Fe]+.
3.11. 3-(4-Acetoxyphenyl)-5-ferrocenyl-1-phenyl-1H-pyrazole (8b)
To a stirred solution of 3-(p-acetoxyphenyl)-5-ferrocenyl-1-
phenyl-4,5-dihydro-1H-pyrazole (7b, 70 mg, 0.151 mmol) in ben-
zene (10 mL) was dropped a solution of DDQ (61 mg, 0.269 mmol)
in benzene (5 mL) and the mixture was refluxed for 2 h, by which
time TLC (solvent A) indicated complete reaction. The suspension
was filtered through Silica gel and washed with dichloromethane
and subsequently dichloromethane–ethyl-acetate (95:5). The fil-
trates were evaporated and purified by repeated column chroma-
tography using dichloromethane and then dichloromethane–
ethyl-acetate (98:2). Crystallization from dichloromethane by add-
ing a few petroleum ether resulted in pure 8b (50 mg, 72%) as or-
ange crystals, m.p. 187–188 °C; Rf 0.27 (solvent A). Anal. Calc. for
C27H22FeN2O2 (462.33): C, 70.14; H, 4.80; N, 6.06. Found: C,
69.78; H, 5.01; N, 6.36. MS: 462(64) M+, 420(24) [M–42]+, 397(2)
[M–C5H5]+, 210(2) [FcC2H]+, 121(32) [CpFe]+, 56(9) [Fe]+, 43(100)
Ac+.
3.14. 5-Ferrocenyl-3-phenyl-1-(2-pyridyl)-4,5-dihydro-1H-pyrazole
(13a)
Preparation of this compound was described earlier [7].
MS: 407(56) M+, 405(16) [M–H2]+, 340(33) [M–H2–C5H5]+,
342(19) [M–C5H5]+, 314(11) [M–R0NH]+, 304(100) [M–RPhCN]+,
286(4) [M–FeCp]+, 212(21) [FcC2H3]+, 121(90) [CpFe]+, 56(34) [Fe]+.
3.15. 3-Ferrocenyl-5-phenyl-1-(2-pyridyl)-4,5-dihydro-1H-pyrazole
(13b)
Preparation of this compound was described earlier [7].
MS: 407(100) M+, 405(18) [M–H2]+, 342(37) [M–C5H5]+, 314(5)
[M–R0NH]+, 304(7) [M–RPhCN]+, 250(7) [M–C5H5–R0N]+, 211(23)
[FcCN]+, 121(49) [CpFe]+, 56(25) [Fe]+.
3.12. 3-(4-Acetoxyphenyl)-5-ferrocenyl-1-(2-pyridyl)-4,5-dihydro-
1H-pyrazole (9b)
4. Supplementary data
To the solution of compound 6 (0.50 g, 1.5 mmol) in a mixture
of ethanol (6 mL), acetic acid (3 mL) and water (3 mL) was added
2-hydrazinopyridine (0.343 g, 3.14 mmol) and the solution was
heated under reflux in nitrogen atmosphere for 5 h and then al-
lowed to stand at RT for 20 h. As TLC (solvent D) showed incom-
plete reaction, further amount of 2-hydrazinopyridine (0.21 g,
1.9 mmol), ethanol (3 mL), acetic acid (1.5 mL) and water
(1.0 mL) was added to the mixture and heating was continued
for further 7 h. On cooling yellow crystals separated, which were
filtered and washed with cold methanol–water (1:1) to give
0.373 g (58.6%) of the 3-(p-hydroxy-phenyl)-5-ferrocenyl-pyrazo-
CCDC 735603 and 735604 contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
Acknowledgements
This work was supported by the Hungarian Scientific Research
Fund (OTKA T-043634, K60679 and K68887). The authors express
their thanks to Dr. Medzihradszky-Schweiger for analyses.
line derivative (12, see at 9b, but R = p-OH, R0 =
a-Py). Acetylation
of crude 12 was made by stirring in a mixture of acetic anhydride
(1.3 mL) and pyridine (2.2 mL) for 4 h at RT and then storing the
reaction at 0 °C for 20 h. The separated yellow crystals were fil-
tered, washed with methanol–water (1:1) and recrystallized from
ethyl-acetate–n-hexane to give pure 9b (0.349 g, 50%, yield calcu-
lated for chalcone 6), m.p. 199–200 °C; Rf 0.34 (solvent C). Anal.
Calc. for C26H23FeN3O2 (465.33): C, 67.11; H, 4.98; N, 9.03. Found:
References
[1] B. Fábián, A. Csámpai, T.Zs. Nagy, M. Czugler, P. Sohár, Synthesis, ring trans-
formations, IR-, NMR- and DFT -study of heterocycles with two ferrocenyl units.
Study on ferrocenes, Part 22. J. Organomet. Chem. 694 (2009) 3732–3741.
[2] (a) L. Jet, in: A.R. Katritzky, C.A. Ramsden, E.F.V. Scriven, R. Taylor (Eds.),
Comprehensive Heterocyclic Chemistry III, vol. 4, Elsevier, Oxford, 2008, pp. 1–
141. and references therein;

V. Zsoldos-Mády et al. / Journal of Organometallic Chemistry 694 (2009) 4185–4195
4195
(b) J. Elguero, in: CHCC II, vol. 3, 1996, pp. 1–75.;
(b) A.M. Osman, K.M. Hassan, M.A. EL-Maghraby, Indian J. Chem. 14B (1976)
282–285. CAN 85:160286; AN 1976:560286.
[19] B. Stanovnik, J. Svete, Sci. Synth. 12 (2002) 15–225. and references therein.
[20] W. Ried, R. Lantzsch, Chem. Ber. 102 (1969) 378–379.
(c) K. Kirschke, in: E. Schaumann (Ed.), Houben-Weyl: Methoden der
Organischen Chemie, vol. E8b, Thieme, Stuttgart, 1994, pp. 399–763.;
(d) A. Lévai, Chemistry of Heterocyclic Compounds, vol. 33, Springer, New
York, 1997.
[21] S. Mallouk, K. Bougrin, H. Doua, R. Benhida, M. Soufiaoui, Tetrahedron Lett. 45
(2004) 4143–4148. and references therein.
[3] D. Azarifar, H. Gasemnejad, Molecules
8 (2003) 642–648. and references
}
therein. CAN 141:54242; AN 2004:563443.
[22] A. Lévai, A.M.S. Silva, D.C.G.A. Pinto, J.A.S. Cavaleiro, I. Alkorta, J. Elguero, J. Jeko,
[4] J.P. Dunn, J.H. Hogg, T. Mirzadegan, S. Swallow, PCT Int. Appl. (2004). WO 2004-
EP1477 20040217. CAN 141:243549; AN 2004:718518.
[5] A. Madin, M.P. Ridgill, PCT Int. Appl. (2004). WO 2004039370 A1 20040513.
CAN 140:406803; AN 2004:387261.
Eur. J. Org. Chem. (2004) 4672–4679. and references therein.
[23] (a) K. Fukui, Molecular Orbitals in Chemistry, Physics and Biology, Academic,
New York, 1964;
(b) K. Fukui, Acc. Chem. Res. 4 (1971) 57–64;
[6] J.R. Pruitt, D.J.P. Pinto, R.A. Galemmo Jr., R.S. Alexander, K.A. Rossi, B.L. Wells, S.
Drummond, L.L. Bostrom, D. Burdick, R. Bruckner, H. Chen, A. Smallwood, P.C.
Wong, M.R. Wright, S. Bai, J.M. Luettgen, R.M. Knabb, P.Y.S. Lam, R.R. Wexler, J.
Med. Chem. 46 (2003) 5298–5315.
(c) K. Fukui, Acc. Chem. Res. 14 (1981) 363–368.
[24] (a) R.G. Parr, W. Yang, Density Functional Theory of Atoms and Molecules,
University Press, New York, 1989;
(b) T. Zeigler, Chem. Rev. 91 (1991) 651–667.
[7] V. Kudar, V. Zsoldos-Mády, K. Simon, A. Csámpai, P. Sohár, J. Organomet. Chem.
690 (2005) 4018–4026. and references therein.
[8] E.I. Klimova, E.A. Vázquez López, T. Klimova, C.A. Toledano, R.A. Toscano, M.
Martinez Garcia, J. Heterocyclic. Chem. 42 (2005) 265–271. and references
therein.
[9] L. Delhaes, H. Abessolo, C. Biot, L. Berry, P. Delcourt, L. Maciejewski, J. Brocard,
D. Camus, D. Dive, Parasitol. Res. 87 (2001) 239–244. PubMed ID 11293573;
AN 2001323549.
[25] (a) P. Senet, J. Chem. Phys. 107 (1997) 2516–2524;
(b) R. Contreras, P. Fuentealba, M. Galván, P. Pérez, Chem. Phys. Lett. 304
(1999) 405–413;
(c) P. Fuentealba, P. Pérez, R. Contreras, J. Chem. Phys. 113 (2000) 2544–2551.
[26] (a) A.D. Becke, J. Chem. Phys. 98 (1993) 5648–5652;
(b) C. Lee, W. Yang, R.G. Parr, Phys. Rev. B 37 (1988) 785–789.
[27] W.J. Hehre, L. Radom, P.V.R. Schleyer, J.A. Pople, Ab initio Molecular Orbital
Theory, Wiley, New York, 1986.
[10] J. Fang, Z. Jin, Z. Li, W. Liu, J. Organomet. Chem. 674 (2003) 1–9. and references
therein.
[11] (a) D.R. van Staveren, N. Metzler-Nolte, Chem. Rev. 104 (2004) 5931–5985;
(b) K.E. Dombrowski, W. Baldwin, J.E. Sheats, J. Organomet. Chem. 302 (1986)
281–306.
[12] (a) M. Zora, A.N. Pinar, M. Odabasoglu, O. Büyükgüngör, G. Turgut, J.
Organomet. Chem. 693 (2008) 145–154. and references therein;
(b) N. Karadayt, G.T. Chin, S. Demirel, A. Cakici, O. Büyükgüngör, Acta
Crystallogr. E 65 (2009) m127–m128. and references therein.
[13] Á. Abrán, A. Csámpai, Z. Böcskei, P. Sohár, Tetrahedron 55 (1999) 5441–5448.
[14] V. Zsoldos-Mády, A. Csámpai, R. Szabó, E. Mészáros-Alapi, J. Pásztor, F. Hudecz,
P. Sohár, ChemMedChem 1 (2006) 1119–1125.
[28] (a) G. Klopman, J. Am. Chem. Soc. 90 (1968) 223–234;
(b) L. Salem, J. Am. Chem. Soc. 90 (1968) 543–552.
[29] (a) P. Sohár, Nuclear Magnetic Resonance Spectroscopy, vol. 2, CRC Press, Boca
Raton, Florida, 1983. p. 90;
(b) P. Sohár, Nuclear Magnetic Resonance Spectroscopy, vol. 1, CRC Press, Boca
Raton, Florida, 1983. p. 35;
(c) P. Sohár, Nuclear Magnetic Resonance Spectroscopy, vol. 1, CRC Press, Boca
Raton, Florida, 1983. p. 69;
(d) P. Sohár, Nuclear Magnetic Resonance Spectroscopy, vol. 2, CRC Press, Boca
Raton, Florida, 1983. p. 153.
[30] F.W. Wehrli, T. Wirthlin, Interpretation of Carbon-13 NMR Spectra, Heyden,
London, 1976. p. 36.
[15] L. Ga˘ina˘, A. Csámpai, Gy. Túrós, T. Lovász, V. Zsoldos-Mády, I.A. Silberg, P.
[31] E. Pretsch, T. Clerc, J. Seibl, N. Simon, Tabellen zur Strukturaufklärung
organischer Verbindungen mit spektroskopischen Methoden, Springer,
Berlin, 1976. p. C120.
[32] A.N. Nesmeyanov, D.V. Zagorevskii, Y.S. Nekrasov, V.N. Postnov, A.M. Baran, J.
Organomet. Chem. 201 (1980) 293–300.
Sohár, Org. Biomol. Chem. 4 (2006) 4375–4386.
[16] (a) A.R. Katritzky, M. Wang, S. Zhang, M. Voronkov, P. Steel, J. Org. Chem. 66
(2001) 6787–6791. and references therein;
(b) D.C.G.A. Pinto, A.M.S. Silva, J.A.S. Cavaleiro, J. Elguero, Eur. J. Org. Chem.
(2003) 747–755. and references therein;
(c) P.W. Kenny, M.J.T. Robinson, Tetrahedron Lett. 27 (1986) 6277–6280.
[17] E.I. Klimova, G.M. Martinez, B.T. Klimova, Z.C. Damian, S. Ortega, I.D. Mendez,
P.R. Gutiérrez, G.R.A. Vazquez, Synthesis 13 (2002) 1891–1897. and references
therein.
[33] teXsan for Windows version 1.06: Crystal Structure Analysis Package,
Molecular Structure Corporation (1997–1999).
[34] G.M. Sheldrick, University of Göttingen, Germany, 1997.
[35] H.D. Flack, Acta Crystallogr. A. 39 (1983) 876–881.
[36] K. Shibata, I. Katsuyama, M. Matsui, H. Muramatsu, Bull. Chem. Soc. Jpn. 63
(1990) 3710–3712. and references therein. CAN 114:102321; AN
1991:102321.
[18] (a) A.N. Nesmeyanov, V.N. Postnov, V.N. Klimova, V.A. Szazonova, Izv. Akad.
Nauk. SzSzSzR. Ser. Khim. (1979) 239–242. CAN 90:168710; AN 1979:168710;