Synthesis and unusual ring transformation of 1-acyl-3- (ferrocenylmethylidene)-piperazine-2,5-diones

Article abstract of DOI:10.1016/j.jorganchem.2013.08.019

The reaction of 1,4-diacyl-piperazine-2,5-diones with ferrocenecarbaldehyde in the presence of ^tBuOK in ^tBuOH-DMF at room temperature afforded 1-acyl-3-(ferrocenylmethylidene)-piperazine-2,5-diones in 69-79% yields. The attempted N(4)-acylation of these compounds with carboxylic acids (2 equiv.) in the presence of N,N′-diisopropylcarbodiimide (2 equiv.) and 4-(dimethylamino)pyridine (3 equiv.) in dichloromethane at room temperature showed that the expected 1,4-diacylated products are initially formed, but undergo further transformations leading to compounds featuring conjugated ferrocenylmethylidene, azlactone (oxazolone) and oxazole units. As shown on the basis of one example, the azlactone ring in these compounds is opened in a room-temperature reaction with hydrazine, thus yielding the corresponding acyl hydrazide. The crystal structure of the starting material and the product of this reaction were confirmed by X-ray diffraction.

Full text of DOI:10.1016/j.jorganchem.2013.08.019

Journal of Organometallic Chemistry 745-746 (2013) 373e378
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Synthesis and unusual ring transformation of 1-acyl-3-
(
ferrocenylmethylidene)-piperazine-2,5-diones
Anna Wieczorek , Damian Pla z_ uk , Janusz Zakrzewski *, Anna Makal b,
a
a
a,
b
Krzysztof Wo ꢀz niak
Department of Organic Chemistry, Faculty of Chemistry, University of Łód ꢀz , Tamka 12, 91-403 Łód ꢀz , Poland
a
b
Faculty of Chemistry, Warsaw University, ul. Pasteura 1, 02-093 Warszawa, Poland
a r t i c l e i n f o
a b s t r a c t
t
Article history:
Received 30 May 2013
Received in revised form
The reaction of 1,4-diacyl-piperazine-2,5-diones with ferrocenecarbaldehyde in the presence of BuOK in
t
BuOHeDMF at room temperature afforded 1-acyl-3-(ferrocenylmethylidene)-piperazine-2,5-diones in
9e79% yields. The attempted N(4)-acylation of these compounds with carboxylic acids (2 equiv.) in the
6
31 July 2013
0
presence of N,N -diisopropylcarbodiimide (2 equiv.) and 4-(dimethylamino)pyridine (3 equiv.) in
dichloromethane at room temperature showed that the expected 1,4-diacylated products are initially
formed, but undergo further transformations leading to compounds featuring conjugated ferroce-
nylmethylidene, azlactone (oxazolone) and oxazole units. As shown on the basis of one example, the
azlactone ring in these compounds is opened in a room-temperature reaction with hydrazine, thus
yielding the corresponding acyl hydrazide. The crystal structure of the starting material and the product
of this reaction were confirmed by X-ray diffraction.
Accepted 8 August 2013
Keywords:
Ferrocene
Piperazine-2,5-dione
Azlactone
Oxazole
Ring-opening
Cyclization
Ó 2013 Elsevier B.V. All rights reserved.
1. Introduction
enhanced anti-microtubule and anticancer properties, similar to or
higher than those of 2.
The search for ferrocenyl compounds exhibiting anticancer ac-
tivity [1e5] continues to be an appealing current field within bio-
organometallic chemistry [6e12]. From a synthetic viewpoint the
main effort has been focused on modifying known anticancer drugs
by introducing cytotoxic ferrocenyl groups into their structures.
The best known example of such an approach is synthesis of the
ferrocifene family, ferrocenyl analogs of an anti-breast cancer drug
e tamoxifen [13].
By continuing our research on cytotoxic ferrocenyl compounds
[14e17], we became interested in the synthesis of ferrocenyl de-
rivatives of 2,6-dimethylenepiperazine-2,5-dione 1. Compounds
having this skeleton are abundant in nature [18,19] and display a
wide spectrum of biological activities. Plinabulin (NPI-2355) 2 ex-
hibits strong anti-microtubule activity and cytotoxicities in the
nanomolar range [20e22]; it is currently under phase 2 clinical
trials as a vascular disrupting agent (VDA) [23]. We thought that
type 1 compounds having a cytotoxic ferrocene moiety attached to
We intended to prepare compounds 1 via a common route, a
two-fold aldol condensation of 1,4-diacetyl-piperazine-2,5-dione
Scheme 1, 4a) (prepared from glycine anhydride 3) with appro-
(
priate aldehydes [18,21,24]. However, during the course of the
synthetic work, we have found that the product of the condensa-
tion of 4a with ferrocenecarbaldehyde, 1-acetyl-3-(ferrocenylme-
0
thylidene)-piperazine-2,5-dione 5a, treated with acetic acid, N,N -
a
3,6-dimethylene-piperazine-2,5-dione template would have
diisopropylcarbodiimide (DIC) and 4-(dimethylamino)pyridine
(DMAP) underwent an unusual transformation into compound 7a
featuring two oxazole rings. Similar reaction was observed with
various carboxylic acids. Herein we wish to report preliminary re-
sults concerning the scope and mechanism of this reaction.
*
Corresponding author.
E-mail address: janzak@uni.lodz.pl (J. Zakrzewski).
0
022-328X/$ e see front matter Ó 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jorganchem.2013.08.019

374
A. Wieczorek et al. / Journal of Organometallic Chemistry 745-746 (2013) 373e378
0
Scheme 1. Synthesis of compounds 5aed and their transformation into 7aed; DIC ¼ N,N -diisopropylcarbodiimide; DMAP ¼ 4-(dimethylamino)pyridine.
2
. Results and discussion
To gain insight into the substrate scope of the discovered reac-
tion we synthesized a series of 1,4-diacyl-piperazine-2,5-diones
4bed by refluxing piperazine-2,5-dione (glycine anhydride) with
corresponding acid anhydrides (reactions performed without a
solvent). The desired 4bed were isolated in excellent yields. These
compounds reacted with ferrocenecarbaldehyde under the condi-
tions described above for the synthesis of 5a, thus giving the ex-
pected 3-ferrocenylmethylene derivatives 5bed in good yields
(72e77%). Then we performed a reaction of 5bed with carboxylic
acids (having the same R group as the substrate to avoid the
eventual formation of regioisomeric 2,5-disubstituted oxazoles) in
the presence of DIC and DMAP. We isolated compounds 7bed,
albeit in lower yields (10e13%).
A plausible mechanism for the transformation 6aed / 7ae
d of is proposed in Scheme 2. Its key step involves C(6)-acylation,
formation of a bicyclic oxazoloepiperazine intermediate, opening
of the piperazine ring and re-cyclization yielding azlactone
moiety.
Compounds 7aed contain a reactive azlactone (oxazolone) ring
which opens up numerous possibilities for synthetic trans-
formations [25e28]. We performed a reaction of 7a with hydrazine,
yielding hydrazide 8 featuring an N-acylated ferrocenyl anhy-
droalanine skeleton in 96% yield (Scheme 3).
2.1. Chemical synthesis
We have found that 4a reacts with ferrocenecarbaldehyde in
t
t
the presence of BuOK in BuOHeDMF at room temperature to
afford the expected 3-ferrocenylmethylidene derivative 5a in 79%
yield.
However, attempts to attach a second unsaturated group to C(6)
via reaction of 5a with various heteroaromatic aldehydes gave only
trace amounts of the expected products. A similar decrease in
reactivity of type 5 monounsaturated piperazine-2,5-diones in a
second aldol condensation was reported earlier [21]. Since we
thought that this may be due to decreased reactivity of the C(6)
methylene group resulting from deacetylation of N(4), we tried to
re-acetylate this nitrogen with acetic anhydride, but the reaction
afforded only trace amount of the desired compound.
Therefore, we decided to check the reaction of 5a with acetic acid
0
in the presence of N,N -diisopropylcarbodiimide (DIC) and 4-(dime-
thylamino)pyridine (DMAP). The reaction was performed in
dichloromethane at room temperature at the molar ratio of 5a:
AcOH:DIC:DMAP ¼ 1:2:3:3 and monitored by TLC. Surprisingly, we
found that although the expected 1,4-diacetyl derivative 6a was
initially formed (and was isolated as red crystals in 40% yield when
the reaction was quenched after 1 h), it underwent subsequent
transformation on overnight standing into blue microcrystalline
oxazole-substituted unsaturated azlactone 7a, isolated in a 44% yield.
Control experiment showed that transformation 6a / 7a takes place
only in the presence of all reactants (i.e. acid, DIC and DMAP). We
attempted to stop the reaction at the formation of 6a using equimolar
amounts of reactants, but under these conditions it was formed in a
deceptively low yield (<5%).
2.2. X-ray structure of 7a and 8
Unambiguous identification of compound 7a and 8 required,
apart from spectroscopic data, a single-crystal X-ray structure
(Figs. 1 and 2, respectively).
The structure of 7a shows the (Z)-configuration of the exocyclic
(C11eC12) ethylene bond. The tricyclic system composed of a
substituted Cp ring, C11 and two oxazole rings is practically planar,
The chemistry of piperazine-2,5-diones has been extensively
studied and various ring-opening reactions were reported [18,24].
However, to the best of our knowledge what we report in this work
e a ring opening followed by a domino reaction forming two
conjugated oxazole rings e is unprecedented.
thus indicating the
p
-conjugation between these units that brings
max 544 nm,
about the intense color of this compounds (
l
3
ꢀ1
ꢀ1
3
¼ 4654 dm mol cm in 1,2-dichloroethane).
The structure of 8 reveals a distortion from the expected
coplanarity of the Cp ligand with the adjacent unsaturated acyl

A. Wieczorek et al. / Journal of Organometallic Chemistry 745-746 (2013) 373e378
375
O
O
O
R
O
O
R
O
O
O
+
-
Fc
N
R
O
R
Fc
R
N
O
Fc
N
N
N
R
N
R
R
C(6)-acylation
O
O
O
O
6a-d
O
R
O
R
O
R
H+
+
+
+
Fc
R
N
Fc
R
N
Fc
R
N
O
O
O
-
H2O
N
N
N
-
O
O
O
O
O
O
O
R
R
R
O
O
+
Fc
O
Fc
O
O
N
N
N
R
O
R
N
R
R
N
N
N
O
O
R
-
R
7a-d
N+
Scheme 2. Plausible mechanism for the transformation 6aed / 7aed.
hydrazide system; whereas the plane of the ethylenic (C11eC12)
4. Experimental section
ꢁ
bond is twisted by about 9 , the carbonyl group plane forms an
ꢁ
angle of about 55 with this plane. On the other hand, the carbonyl
4.1. General
group is practically coplanar with the oxazole ring (an angle of
about 6 ). These distortions are probably of steric origin.
ꢁ
1H and 13C NMR spectra were recorded on a Bruker ARX 600
1
13
spectrometer (600 MHz for H and 151 MHz for C). Chemical
1
shifts in H spectra were referenced relative to the solvent signals:
1
13
3
. Conclusion
CDCl
3
d
¼ 7.27 ppm for H and
d
¼ 77.20 ppm for C. Spectra were
recorded at room temperature (291 K), chemical shifts are in ppm
and coupling constants in Hz. EI and HR-EI and HRMS-EI analyses
were performed in positive mode at 75 eV on mass spectrometer
In conclusion, we discovered an unusual reaction of 1-acyl-3-
ferrocenylmethylene-piperazine-2,5-diones involving ring-open
ing followed by a domino cyclization that forms two oxazole
rings. The reactive oxazolone moiety that is present in the products
of this reaction (7aed) is expected to undergo various ring-opening
reactions (as evidenced by the reaction of 7a with hydrazine) which
may open up new routes to ferroceneepeptido conjugates.
Furthermore, the oxazolone ring may also serve as a template in
diversity-oriented synthesis of heterocycles [29e33] and natural
products [25e34]. Finally, 7aed are potential redox-active biden-
tate ligands for metal ions.
Fig. 1. ORTEP view of 7a. Thermal ellipsoids have been set at the 50% probability level.
ꢁ
ꢁ
Selected bond distances (A) and dihedral angles ( ): C11eC12 1.3545(19); C12eN1
.4097(18); N1eC14 1.2892(18); C14eO2 1.3891(16); O2eC13 1.3891(16); C13eO1
.2015(17); C14eC15 1.4461(19); C15eN2 1.4028(18); N2eC18 1.2907(18); C18eC19
.482(2); C18eO3 1.3753(17); O3eC16 1.3740(16); C16eC17 1.478(2); C15eC16
.3615(19); C12eC11eC6eC10 7.3(2); C6eC11eC12eN1 ꢀ1.4(2); N1eC14eC15eN2
0.2(2) (for detailed crystallographic data see the Supplementary materials).
1
1
1
1
Scheme 3. Ring-opening reaction of azlactone 7a with hydrazine.

376
A. Wieczorek et al. / Journal of Organometallic Chemistry 745-746 (2013) 373e378
2
CH
ꢂ CH
2
-
b
); 1.33e1.42 (m, 4H, 2ꢂ CH
). C NMR: 174.26 (CO); 166.05 (CO); 47.68 (C-3 and C-6);
); 26.62 (CH ); 22.37 (CH ); 13.95 (CH );
2
-
g
); 0.93 (t, J ¼ 7.3, 6H, 2ꢂ
1
3
3
d
38.71 (CH
2
-a
2
-b
2
-g
3
Elemental analysis: Found: C, 59.52; H, 7.91; N, 9.89; C14
requires: C, 59.56; H, 7.85; N, 9.92.
22 2 4
H N O
4.1.4. 1,4-Dihexanoylpiperazine-2,5-dione (4d)
It was prepared using the same procedure as 4a starting from
3
1
.50 g (13 mmol) of glycine anhydride and 15 cm of hexanoic
1
anhydride. Yield: 3.80 g (94%). White powder. H NMR:
d
4.58 (s,
); 1.63e1.71 (m, 4H,
and 2ꢂ CH ); 0.87e0.94
174.30 (CO); 166.06 (CO); 47.69 (C-3
); 31.42 (CH or ); 24.24 (CH ); 22.57
); 14.05 (CH ). Elemental analysis: Found: C, 61.78; H,
.42; N, 9.07. C16 requires: C, 61.91; H, 8.44; N, 9.03.
4
H, H-3 and H-6); 2.95 (t, J ¼ 7.5, 4H, 2ꢂ CH
2
-a
2
ꢂ CH ); 1.31e1.37 (m, 8H, 2ꢂ CH
2
-b
2
-
g
2
-d
13
(
m, 6H, 2ꢂ CH
and C-6); 38.98 (CH
CH or
3
). C NMR: d
2
-a
2
-g
d
2
-b
(
2
-
g
d
3
8
26 2 4
H N O
4.1.5. 1-Acetyl-3-ferrocenylmethylidene-2,5-piperazinedione (5a)
Potassium t-butoxide (0.74 g, 6.6 mmol) was added to a solution
of 4a (1.31 g, 6.6 mmol) and ferrocenecarbaldehyde (1.00 g,
.7 mmol) in the mixture of DMF (12 ml) and tert-butanol (15 ml).
The resulting mixture was stirred at room temperature overnight
and the reaction was quenched by adding of H O (50 ml) and acetic
acid (5 ml). The product was extracted with dichloromethane, the
extract washed with water, brine, dried over Na SO and evapo-
4
Fig. 2. ORTEP view of 8. Thermal ellipsoids have been set at the 50% probability level.
ꢁ
ꢁ
Selected bond distances (A) and dihedral angles ( ): C1eC11 1.465(3); C11eC12
.339(3); C12eC13 1.498(3); C13eN1 1.331(3); N1eN2 1.419(2); C12eN3 1.410(2); N3e
C14 1.360(3); C14eO1 1.227(2); C14eC15 1.470(3); C15eC16 1.347(3); C16eC17
.473(3); C16eO3 1.378(2); O3eC18 1.369(3); C18eC19 1.487(3); C18eN4 1.284(3);
2
1
2
4
1
N4eC15 1.403(3); C5eC1eC11eC12 25.4(3); C1eC11eC12eC13 171.17(19); C11eC12e
C13eO2 ꢀ125.3(2); N3eC12eC13eO2 40.8(3); C13eC12eN3eC14 42.7(3); C12eN3e
C14eO1 5.7(3); O1eC14eC15eC16e1.2(3) (for detailed crystallographic data see the
Supplementary materials).
rated to dryness. The crude product was purified by column chro-
matography on silica gel using dichloromethaneeethyl acetate
(
10:1) as eluent and then crystallized from ethyl acetateen-hexane.
1
Yield: 1.31 g (79%). Red crystals. H NMR: d 8.14 (br. s., 1H, NH); 6.95
(
s, 1H, H-vinyl); 4.49 (s, 6H, 4ꢂ H-Cp and H-6); 4.24 (s, 5H, Cp); 2.63
13
Finnigan MAT 95, Elemental analysis was performed by the Labo-
ratory of Microanalysis at the Centre of Molecular and Macromo-
lecular Studies in qód ꢀz , Poland. Thin-layer chromatography (TLC)
3
(s, 3H, CH ). C NMR: d 172.7 (CO); 162.5 (CO); 160.1 (CO); 123.5 (C-
3); 121.0 (CH-vinyl); 75.9 (Cp-ipso); 71.2 (Cp); 69.9 (Cp); 69.6 (Cp);
46.4 (C-6); 27.3 (CH ); Elemental analysis: Found: C, 57.95; H, 4.62;
N, 7.92. C17 16FeN requires: C, 57.98; H, 4.58; N, 7.95.
3
was performed on aluminum sheets precoated with Merck 5735
Kieselgel 60F254. Column chromatography was carried out on silica
gel 60 (0.040e0.063 mm, 230e400 mesh, Fluka). Dichloromethane
was distilled from calcium hydride and stored over activated mo-
lecular sieves 4 A (8e12 mesh). Reactions with ferrocenyl com-
pounds were carried out under argon using the standard Schlenk
technique. Chemicals and solvents (HPLC grade) were purchased
from SigmaeAldrich or AK Scientific (USA) and used as received.
H
2 3
O
4.1.6. 3-Ferrocenylmethylidene-1-isobutyrylpiperazine-2,5-dione
(5b)
It was prepared using the same procedure as 5a starting from 4b
1
(1.67 g, 6.6 mmol). Yield: 1.19 g (67%). Red crystals. H NMR:
d 8.06
(s, 1H, NH); 6.96 (s, 1H, CH-vinyl); 4.49 (s, 2H, Cp); 4.48 (s, 2H, Cp);
4.47 (s, 2H, H-6); 4.25 (s, 5H, Cp); 3.71 (dt, J ¼ 13.6, 6.8,1H, CH); 1.24
1
3
(
d, J ¼ 6.8, 6H, 2ꢂ CH
3
); C NMR: d 180.8 (CO); 162.9 (CO); 160.1
4.1.1. 1,4-Diacetylpiperazine-2,5-dione (4a)
(CO); 123.8 (C-3); 120.9 (C-vinyl); 76.1 (Cp-ipso); 71.2 (Cp); 69.9
(Cp); 69.6 (Cp); 48.1; 46.8 (C-6); 36.2 (CH); 19.7 (CH ); Elemental
requires: C,
A mixture of glycine anhydride 1.50 g (13 mmol) and acetic
3
ꢁ
anhydride (15 ml) was heated at 220 C (oil bath temperature) for
analysis: Found: C, 59.96; H, 5.51; N, 7.31. C19
2 3
H20FeN O
2
h. The resulting solution was then cooled and an excess of acetic
60.02; H, 5.30; N, 7.37.
anhydride was removed under reduced pressure. The crude prod-
uct was crystallized from n-hexaneeethyl acetate (1:1) Yield: 3.62 g
4.1.7. 3-Ferrocenylmethylidene-1-pentanoylpiperazine-2,5-dione
(
79%) of a bright yellow crystals. NMR and IR spectra of the product
(5c)
were identical with those of an authentic sample [34].
It was prepared using the same procedure as 5a starting from 4c
1.86 g, 6.6 mmol). Yield: 1.34 g (72%). Orange crystals. H NMR:
1
(
4
.1.2. 1,4-Diisobutyrylpiperazine-2,5-dione (4b)
It was prepared using the same procedure as 4a, starting from
.00 g (26 mmol) of glycine anhydride and 30 cm of isobutyric
d
8.1 (s, 1H, NH); 6.94 (s, 1H, CH-vinyl); 4.49 (s, 2H, H-6); 4.49 (d,
J ¼ 1.9, 2H, Cp); 4.48 (d, J ¼ 1.9, 2H, Cp); 4.25 (s, 5H Cp); 3.00 (t,
J ¼ 7.2, 2H, CH ); 1.69 (dt, J ¼ 15.1, 7.5, 2H, CH ); 1.37e1.45 (m,
2H, CH 176.1 (CO); 162.7
); 0.96 (t, J ¼ 7.3, 3H, CH
(CO); 160.1 (CO); 123.7 (C-3); 120.7 (CH-vinyl); 76.0 (Cp-ipso); 71.2
(Cp); 69.9 (Cp); 69.5 (Cp); 46.5 (C-6); 39.1 (CH ); 27.1 (CH );
22.5 (CH ); 14.0 (CH ); Elemental analysis: Found: C, 60.98;
H, ꢀ5.71; N, 7.09. C20 22FeN requires: C, 60.93; H, 5.62; N, 7.11.
3
3
2
-a
2
-b
1
13
anhydride. Yield: 5.70 g (85%). Bright yellow powder. H NMR:
d
4.58
2
-
g
3
); C NMR: d
(
1
6
s, 4H, H-3 and H-6); 3.68 (dt, J ¼ 13.5, 6.8, 2H, 2ꢂ CH); 1.21 (d, J ¼ 6.8,
1
3
2H, 4ꢂ CH
3
). C NMR:
d
178.71 (CO); 165.93 (CO); 48.13 (C-3 and C-
2
-a
2
-b
); 36.04 (CH); 19.27 (CH
3
); Elemental analysis: Found: C, 56.65; H,
requires: C, 56.68; H, 7.13, N, 11.02.
2
-
g
3
7.13. N, 10.87. C12
H
18
N
2
O
4
H
2 3
O
4
.1.3. 1,4-Divalerylpiperazine-2,5-dione (4c)
It was prepared using the same procedure as 4a starting from
4.1.8. 3-Ferrocenylmethylidene-1-hexanoylpiperazine-2,5-dione
(5d)
3
1.50 g (13 mmol) of glycine anhydride and 15 cm of valeric an-
It was prepared using the same procedure as 5a starting from 4d
1
1
hydride. Yield: 3.39 (89%). White powder. H NMR:
d
4.58 (s, 4H, H-
(2.05 g, 6.6 mmol). Yield: 1.42 g (74%). Orange crystals. H NMR:
3
and H-6); 2.94 (t, J ¼ 7.3, 4H, 2ꢂ CH ); 1.65 (dt, J ¼ 15.1, 7.53, 4H,
2
-
a
d 8.09 (bs, 1H, NH); 6.94 (s, 1H, CH-vinyl); 4.49 (s, 2H, H-6); 4.49 (t,

A. Wieczorek et al. / Journal of Organometallic Chemistry 745-746 (2013) 373e378
377
Table 1
Crystal data and structure refinement for 7a and 8.
7
a
8
C
Empirical formula
Formula weight
C
19
H
16FeN
2
O
3
19 4 3
H20FeN O
408.24
376.19
Temperature
Wavelength
Crystal system, space group
Unit cell dimensions
100(2) K
0.71073 A
Monoclinic, P-1
100(2) K
0.71073 A
Monoclinic, P 1 21/c 1
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
a ¼ 7.0637(2) A
a
¼ 75.546(3)
a ¼ 9.7340(12) A
a
¼ 90
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
b ¼ 10.7280(4) A
b
g
¼ 80.034(4)
b ¼ 23.8380(5) A
b
¼ 95.436(9)
ꢁ
ꢁ
ꢁ
c ¼ 10.8421(4) A
¼ 79.213(3)
c ¼ 7.7331(4) A
g
¼ 90
ꢁ
3
ꢁ
3
Volume
Z
Calculated density
Absorption coefficient
F(000)
774.62(5) A
2
1786.3(2) A
4
3
3
1.613 mg/m
0.995 mm
388
1.518 mg/m
0.873 mm
848
ꢀ
1
ꢀ1
Crystal size
Theta range for data collection
Limiting indices
Reflections collected/unique
Completeness to theta¼
Absorption correction
Max. and min. transmission
Refinement method
Data/restraints/parameters
0.16 ꢂ 0.04 ꢂ 0.04 mm
0.11 ꢂ 0.08 ꢂ 0.04 mm
ꢁ
ꢁ
2.96e32.31
2.10e28.72
ꢀ10 ꢃ h ꢃ 10, ꢀ15 ꢃ k ꢃ 15, ꢀ15 ꢃ l ꢃ 16
19,709/5182 [R(int) ¼ 0.0349]
32.31; 93.9%
ꢀ12 ꢃ h ꢃ 12, ꢀ31 ꢃ k ꢃ 31, ꢀ10 ꢃ l ꢃ 10
27,218/4429 [R(int) ¼ 0.0471]
25.00; 99.8%
Semi-empirical from equivalents
0.96 and 0.95
Semi-empirical from equivalents
1.0 and 0.97
Full-matrix least-squares on F2
5182/16/290
Full-matrix least-squares on F2
4429/0/273
2
Goodness-of-fit on F
1.036
1.062
Final R indices [I > 2sigma(I)]
R indices (all data)
Largest diff. peak and hole
R1 ¼ 0.0324, wR2 ¼ 0.0690
R1 ¼ 0.0348, wR2 ¼ 0.0703
R1 ¼ 0.0456, wR2 ¼ 0.0739
R1 ¼ 0.0532, wR2 ¼ 0.0848
ꢁ
ꢀ3
ꢁ
ꢀ3
0.515 and ꢀ0.329 e. A
0.419 and ꢀ0.346 e. A
þ
J ¼ 1.9, 2H, Cp); 4.48 (t, J ¼ 1.9, 2H, Cp); 4.25 (s, 5H, Cp); 2.99 (t,
J ¼ 7.5, 2H, CH ); 1.65e1.74 (m, 2H, CH ); 1.28e1.41 (m, 4H,
CH and CH
62.7 (CO); 160.1 (CO); 123.7 (C-3); 120.7 (CH-vinyl); 76.0 (Cp-
ipso); 71.2 (Cp); 69.9 (Cp); 69.5 (Cp); 46.5 (C-6); 39.3 (CH ); 31.5
CH or ); 24.7 (CH ); 22.6 (CH or ); 14.1 (CH ); Elemental
analysis: Found: C, 61.80; H, 6.02; N, 6.82. C21 24FeN O requires: C,
C, 60.66; H, 4.29; N, 7.45. EI-HRMS: Found: 376.0510 (M ).
þ
2
-
a
2
-
b
C
19
H16FeN
2
O
3
requires 376.0500 (M ).
1
3
2
-
g
2 3
-d); 0.84e0.96 (m, 3H, CH ); C NMR: d 176.1 (CO);
0
0
0
1
4.1.11. 4-Ferrocenylmethylidene-2 ,5 -diisobutyryl-[2,4 -bioxazol]-
5(4H)-one (7b)
2
-a
(
2
-
g
d
2
-b
2
-g
d
3
It was prepared using the same procedure as 7a starting from of
H
2
5b (382 mg, 2.0 mmol) and of isobutyric acid (278
m
l, 3.0 mmol).
1
61.78; H, 5.93; N, 6.86.
Yield: 59 mg (14%). Dark purple crystals. H NMR: d 7.22 (s, 1H, CH-
vinyl); 5.06 (s, 2H, Cp); 4.66 (s, 2H, Cp); 4.20 (s, 5H, Cp); 3.83 (td,
0
0
0
4
.1.9. 1,4-Diacetyl-3-ferrocenylmethylidenepiperazine-2,5-dione
J ¼ 7.0, 13.9, 1H, 2 -CH(CH
3
)
2
); 3.16 (td, J ¼ 7.0, 13.9, 1H, 5 -
0
(
6a)
To a solution of 5a (352 mg,1.0 mmol), DMAP (244 mg, 2.0 mmol),
and acetic acid (172 l, 3.0 mmol) in dichloromethane (10 ml), DIC
79 mg (470 l, 3.0 mmol), was added and the resulting solution was
CH(CH
CH(CH
3
)
)
2
); 1.40 (d, J ¼ 7.2, 6H, 2 -CH(CH
3
)
2
); 1.39 (d, J ¼ 7.2, 6H, 5 -
13
0
0
3
2
); C NMR:
d
168.1 (C-5 ); 166.8 (CO); 162.2 (C-2 ); 156.2
0
m
(C-2); 135.7 (CH-vinyl); 129.4 (C-4); 122.4 (C-4 ); 73.1 (Cp); 72.5
(Cp); 70.4 (Cp); 28.7 (5 -CH(CH
0
0
0
3
m
3
)
2
), 26.7 (2 -CH(CH
3
)
2
); 20.7 (2 -
0
stirred at 1 h at room temperature. Then the reaction was quenched
by adding water (20 ml), and the product was extracted with
dichloromethane. The organicsolutionwaswashed with water, brine,
dried and evaporated. The crude product was purified by column
CH(CH
3
)
2
); 20.4 (5 -CH(CH
3
)
2
); Elemental analysis: Found: C, 63.72;
requires: C, 63.90; H, 5.60; N, 6.48.
H, 5.74; N, 6.23. C23
H
24FeN
2
O
3
0
0
0
4.1.12. 4-Ferrocenylmethylidene-2 ,5 -divaleryl-[2,4 -bioxazol]-
5(4H)-one (7c)
chromatography on silica gel using dichloromethaneeethyl acetate
1
(
20:1) as eluent. Red crystals. Yield: 155 mg (40%). H NMR 7.47 (s,1H,
It was prepared using the same procedure as 7a starting from 5c
CH-vinyl), 4.57 (br. s., 2H, H-6), 4.52 (t, J ¼ 1.7 Hz, 2H, Cp-
J ¼ 1.7 Hz, 2H, Cp- ), 4.19 (s, 5H, Cp), 2.59 (s, 3H,1-COCH ), 2.56 (s, 3H,
); C NMR 171.36 (1-COCH ); 167.20 (C-5); 166.94 (4-
); 165.11 (C-2); 138.28 (CH-vinyl); 121.02 (C-3); 75.67 (Cp-
ipso); 72.22 (Cp- ); 70.77 (Cp- ); 70.17 (Cp); 47.00 (C-6); 27.05 (4-
COCH ); 26.08 (1-COCH ); Elemental analysis: Found: C, 57.80; H,
.58; N, 7.10. C19 18FeN requires: C, 57.89; H, 4.60; N, 7.11.
b
), 4.36 (t,
(394 mg, 2.0 mmol) and valeric acid (326 ml 3.0 mmol). Yield: 87 mg
1
a
3
(16%). Purple crystals. H NMR:
d
7.21 (s, 1H, H-vinyl); 5.07 (br. s., 2H,
13
0
4
-COCH
3
3
Cp); 4.64 (s, 2H, Cp); 4.20 (s, 5H, Cp); 3.11 (t, J ¼ 7.7, 2H, 2 -CH
2
-
a
); 2.81
0
0
0
COCH
3
(t, J¼ 7.7, 2H, 5 -CH
2
-
a
); 1.69e1.83(m, 4H, 2 -and5 -CH
2
-
b
); 1.40e1.47
); 0.96 (t, J ¼ 7.3,
0
0
0
b
a
(m, 4H, 2 - and 5 -CH
2
-g); 0.99 (t, J ¼ 7.3, 3H, 2 -CH
3
0
13
0
0
3
3
3H, 5 -CH
3
); C NMR:
d
166.7 (CO); 164.6 (C-5 ); 158.3 (C-2 ); 156.1 (C-
0
4
H
2
O
4
2); 135.7 (CH-vinyl); 129.4 (C-4); 124.1 (C-4 ); 76.6 (Cp-ipso); 73.1
0
0
0
(
CH
Cp); 72.5 (Cp); 70.4 (Cp); 30.0 (2 -CH
2
-b
); 29.2 (5 -CH
2
-
b
); 28.0 (5 -
0
0
0
0
0
0
0
0
4
.1.10. 1,4-Ferrocenylmethylidene-2 ,5 -dimethyl-[2,4 -bioxazol]-
(4H)-one (7a)
2
-a
); 26.2 (2 -CH
2
-
a
); 22.5 (2 - or 5 -CH
2
-g
); 22.4 (2 - or 5 -CH
2
-g
);
0
0
0
0
5
3 3
13.9 (2 - or 5 -CH ); 13.8 (2 - or 5 -CH ); Elemental analysis: Found: C,
Obtained using the procedure described above after overnight
2 3
65.31; H, 6.29; N, 6.01. C25H28FeN O requires C, 65.23; H, 6.13; N, 6.09.
standing of the reaction mixture. Yield: 165 mg (44%). Dark blue
1
0
0
0
crystals. H NMR:
d
7.24 (s, 1H, CH-vinyl); 5.08 (s, 2H, Cp); 4.65 (t,
4.1.13. 4-Ferrocenylmethylidene-2 ,5 -dihexanoyl-[2,4 -bioxazol]-
5(4H)-one (7d)
0
0
J ¼ 1.9, 2H, Cp); 4.20 (s, 5H, Cp); 2.69 (s, 3H, 2 -CH
3
); 2.51 (s, 3H, 5 -
1
3
0
0
CH
3
). C NMR:
d
166.7 (CO); 161.1 (C-5 ); 155.8 (C-2); 154.2 (C-2 );
It was prepared by the same procedure as 7a starting from of 5d
(408 mg, 2.0 mmol) and hexanoic acid (376 ml, 3.0 mmol). Yield:
73 mg (15.0%). Purple crystals. H NMR:
5.07 (br. s., 2H); 4.65 (s, 2H); 4.20 (s, 5H); 3.11 (t, J ¼ 7.5, 2H, 2 -CH
0
136.1 (CH-vinyl); 129.2 (C-4); 124.7 (C-4 ); 76.5 (Cp-ipso); 73.2
0
0
1
(
Cp); 72.6 (Cp); 70.4 (Cp); 14.0 (2 -CH
3
); 12.4 (5 -CH
16FeN
3
); Elemental
: requires:
d
ppm 7.22 (s, 1H, H-vinyl);
0
analysis: Found: C, 60.65; H, 4.32; N, 7.23. C19
H
2
O
3
2
-

378
A. Wieczorek et al. / Journal of Organometallic Chemistry 745-746 (2013) 373e378
0
0
0
0
a
b
CH
(
(
); 2.82 (t, J ¼ 7.7, 2H, 5 -CH
2
-
a
g
); 1.76e1.84 (m, 4H, 2 - and 5 -CH
2
-
Appendix A. Supplementary material
0
); 1.38e1.44 (m, 4H, 2 -CH
2
-
and CH
2
-d
); 1.34e1.38 (m, 4H, 5 -
13
2
-
g
and CH
2
-
d
); 0.88e0.95 (m, 6H, 2ꢂ CH
3
); C NMR:
d
166.7
CCDC 938751 and 938752 contain the supplementary crystal-
lographic date for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via www.
ccdc.cam.uk/data_request/cif.
0
0
CO); 164.6 (C-5 ); 158.3 (C-4 ); 156.1 (C-2); 135.7 (CH-vinyl); 129.4
0
C-4); 124.1 (C-2 ); 76.6 (Cp-ipso); 73.1 (Cp); 72.5 (Cp); 70.4 (Cp);
0
0
0
0
0
0
3
2
5
2
1.54 (2 - or 5 -CH
2
-g
, or 2 - or 5 -CH
2
-
d
); 31.5 (2 - or 5 -CH
2
-
g
, or
0
0
0
0
0
0
0
- or 5 -CH
2
-
d
); 28.3 (5 -CH
2
-
a
); 27.7 (2 - or 5 -CH
2
-
b
); 26.8 (2 - or
0
0
0
0
0
0
-CH
2
-b
); 26.5 (2 -CH
2
-a
); 22.5 (2 - or 5 -CH
2
-
g
, or 2 - or 5 -CH
2
-
d
);
);
References
0
0
0
2.4 (2 - or 5 -CH
2
-g
, or 2 - or 5 -CH
Elemental analysis: Found: C, 66.38; H, 6.89; N, 5.61. C27
requires: C, 66.40; H, 6.60; N, 5.74.
2
-
d
); 14.1 (CH
3
); 14.1 (CH
32FeN
3
H
2
O
3
[1] C. Ornelas, New J. Chem. 35 (2011) 1973e1985.
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[
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SO
4
, and evaporated. Crystallization from dichloro-
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1
H NMR:
Cp); 4.28 (bs, 5H, Cp); 2.59 (s, 3H, CH
71.4; 167.2; 166.9; 165.2; 138.4; 121.0; 72.9; 71.4; 70.9; 47.2; 27.1;
6.1 Elemental analysis: Found: C, 56.01; H, 5.14. C19 20FeN
d
7.42 (bs, 1H, CH); 4.58 (bs, 4H, Cp, NH
2
); 4.45 (bs, 2H,
4
98e501.
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3
); 2.56 (s, 3H, CH ); C NMR:
3
1
1
2
[
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4 3
O
requires: C, 55.90; H, 4.94. Unfortunately we were unable to obtain
a correct value for nitrogen; HRMS (EI): Found: 408.0885 (M ).
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þ
þ
C
19
H20FeN
4
O
3
requires 408.0875 (M ).
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[
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ꢁ
refined with restraint placed on the CeH distance only: 0.95(2) A
ꢁ
for hydrogens bound to aromatic C atoms and 0.98(2) A for hy-
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Acknowledgments
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This research was financially supported by the National Science
Centre (NCN) grant DEC-2011/01/B/ST5/03933.