Synthesis, reactivity, electrochemical and crystallographic studies of diferrocenoyl diselenide and ferrocenoyl selenides

Article abstract of DOI:10.1016/j.jorganchem.2004.06.054

Diacyl diselenide (8), diacyl selenide (9) and acyl selenol esters (10 - 12) incorporating the ferrocenoyl substituent have been synthesized from ferrocene carboxylic acid (13). The new compounds (8- 10) have been characterized by multinuclear NMR (¹H, ¹³C, ⁷⁷Se), IR spectroscopy and electrospray mass spectrometry. All compounds (8 - 13) undergo a one electron reversible oxidation at significantly more positive potential than ferrocene. The structures of the diselenide and selenide (8 and 10) have been confirmed by single crystal X-ray diffraction. The absolute structure parameter of 8 indicates that it crystallizes in an enantiomerically pure form. The peroxidase-like activities of the diselenide (8) and selenides (9 - 12) have been determined by the thiol assay.

Full text of DOI:10.1016/j.jorganchem.2004.06.054

Journal of Organometallic Chemistry 689 (2004) 3046–3055
www.elsevier.com/locate/jorganchem
Synthesis, reactivity, electrochemical and crystallographic studies of
diferrocenoyl diselenide and ferrocenoyl selenides
a
Sangit Kumar , Santosh K. Tripathi , Harkesh B. Singh , Gotthelf Wolmersha¨user
a
a,*
b
a
Department of Chemistry, Indian Institute of Technology, Bombay, Mumbai 400 076, India
b
Fachbereich Chemie, Universita¨t Kaiserslautern, Postfach 3049, Kaiserslautern 67653, Germany
Received 14 May 2004; accepted 29 June 2004
Available online 5 August 2004
Abstract
Diacyl diselenide (8), diacyl selenide (9) and acyl selenol esters (10–12) incorporating the ferrocenoyl substituent have been
synthesized from ferrocene carboxylic acid (13). The new compounds (8–10) have been characterized by multinuclear NMR
(1H, 13C, 77Se), IR spectroscopy and electrospray mass spectrometry. All compounds (8–13) undergo a one electron reversible
oxidation at significantly more positive potential than ferrocene. The structures of the diselenide and selenide (8 and 10) have
been confirmed by single crystal X-ray diffraction. The absolute structure parameter of 8 indicates that it crystallizes in an enan-
tiomerically pure form. The peroxidase-like activities of the diselenide (8) and selenides (9–12) have been determined by the thiol
assay.
ꢀ 2004 Elsevier B.V. All rights reserved.
Keywords: Selenol esters; Ferrocene; Thiol peroxidase; X-ray crystal structures
1. Introduction
eral procedures have been developed to prepare these es-
ters [8,9].
The acyl selenides are useful synthetic intermediates
and are employed as building blocks for the synthesis
of heterocyclic compounds (oxazole, b-lactone) [1],
asymmetric aldol reactions [2] and precursors for acyl
radical chemistry [3,4]. Acyl selenides and selenol esters
can produce acyl radicals under mild conditions, which
can be used in a large variety of inter- and intramolecu-
lar reactions [5]. Acyl selenides are also well known for
their liquid crystalline properties [6]. In recent years,
selenol esters and their analogues have attracted much
attention from chemists interested in aspects of their
structures [7]. Due to their potential applications, sev-
Besides that, selenol esters have also been used as
glutathione peroxidase (GPx) mimics for the decomposi-
tion of hydrogen peroxides [10]. Compounds with a Se–
C bond exhibit significant GPx activity, if the Se–C
bond is easily cleaved by GSH. For example, some sele-
nol esters and a-(arylselenenyl) ketones (1–7) exhibit
glutathione peroxidase-like (GPx) activity by reacting
with GSH to produce catalytically active species (vide
infra). Our group has reported that diselenides having
a ferrocene-like redox active group show much better
activity in the thiol assay than the diselenides based on
benzene [11]. In this paper, we report the synthesis, char-
acterization and the thiol peroxidase-like activity of dif-
errocenoyl diselenide (8), diferrocenoyl selenide (9) and
ferrocenoyl selenol esters (10–12) where the selenium is
not directly attached to a cyclopentadienyl (Cp) ring
(Chart 1).
*
Corresponding
author.
Tel.:
+912225767190;
fax:
+912225723480/25767152.
E-mail address: chhbsia@chem.iitb.ac.in (H.B. Singh).
0022-328X/$ - see front matter ꢀ 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2004.06.054

S. Kumar et al. / Journal of Organometallic Chemistry 689 (2004) 3046–3055
3047
equiv. of I2/KI gave the orange coloured diferrocenoyl
diselenide (8) in 20% yield. Alternatively diferrocenoyl
diselenide (8) was synthesized in good yield (96%) by the
reaction of Li2Se2 [13] and ferrocenoyl chloride. 2:1 Molar
reaction of ferrocenoyl chloride with LiAlHSeH gave the
diferrocenoyl selenide (9) in 90% yield (Scheme 1).
O
O
O
SeR
Ph
PhSe
Se )
R
2
3 R = phenyl
Fe
1 R = methyl
2 R = tbutyl
4 R = 4-OMe-phenyl
5 R = 4-NO2-phenyl
6 R = thienyl
8
The synthesis of diacyl selenides has been a subject of
several recent reports [14]. Jensen et al. [8d] have
reported the existence of unstable dibenzoyl selenide,
which was obtained by the elimination of hydrogen sele-
nide from selenobenzoic acid at room temperature.
Kato et al. [14] have reported the synthesis of diacyl sele-
nides by the reaction of O-silyl selenocarboxylates with
acyl chlorides. Here preparation of diferrocenoyl sele-
nide (9) could be easily achieved in one pot and good
yields. Ferrocenoyl(2-methylnaphthyl) selenide (10)
was synthesized by the reaction of the lithium selenolate
with ferrocenoyl chloride. Bis(2-methylnaphthyl) disele-
nide [15] was reduced by using 2 equiv. of lithium super-
hydride, [Li(C2H5)3BH] to afford the selenolate.
Similarly ferrocenoyl selenol esters 11 and 12 were
synthesized by the reduction of the corresponding dise-
lenides, bis(2,6-dimethyl-4-tert-butylphenyl) diselenide
[11a] and diphenyl diselenide. Ferrocenoyl selenol esters
7 R = naphthyl
O
O
) Se
2
SeR
Fe
Fe
9
10 R = 2-methylnaphthyl
11 R = 2,6-dimethyl-4-tert-butylphenyl
12 R = phenyl
Chart 1. Selenol esters having GPx-like activity.
2. Results and discussion
2.1. Synthesis
The equimolar reaction of ferrocenoyl chloride [12]
with LiAlHSeH [9] and subsequent quenching with 1
Scheme 1. Synthesis routes to diferrocenoyl diselenide (8) and ferrocenoyl selenides (9–12).

3048
S. Kumar et al. / Journal of Organometallic Chemistry 689 (2004) 3046–3055
(10–12) were purified by column chromatography and
obtained in good yields (55–94%).
(10–12) and ferrocene carboxylic acid (13) were investi-
gated by cyclic voltammetery in CH3CN solution.
The electrochemical behavior of ferrocene derivatives
(8–13) is in accordance with the monometallic nature of
the compound. The cyclic voltammogram of diferroce-
noyl diselenide (8) is shown as an example in Fig. 1
and the half wave potentials (E1/2) of compounds (8–
13) are listed in Table 1. Each of the cyclic voltammo-
grams of the ferrocenoyl compounds (8–13) showed a
well-defined single electron wave that was reversible in
nature, although peak separations were generally some-
what greater than the 59 mV expected theoretically
[17,18]. The E1/2 values for these compounds are consid-
erably more positive than the corresponding value for
ferrocene. This may be due to the strong electron with-
drawing nature of the carboxylic and selenol ester
groups, which are bonded directly to the Cp ring, mak-
ing the oxidation more difficult than that of unsubsti-
tuted ferrocene. It is interesting to note here that E1/2
values of diferrocenoyl selenide (9) and ferrocenoyl sele-
nol esters (10–12) are significantly lower than the E1/2
values of 8. The difference in E1/2 between [FcC(O)Se]2
(8) and [FcC(O)]2Se (9) was 39 mV. Morley et al. [17]
have reported that the E1/2 difference between (FcSe)2
and FcSenBu was 80 mV and Shu et al. [18] have re-
ported 125 mV E1/2 difference for the same compounds.
The smaller difference in E1/2 between 8 and 9 as
2.2. NMR and IR spectroscopic studies
1
The H NMR spectra show one singlet (4.28–4.43
ppm) due to the unsubstituted Cp ring and two pseu-
do-triplets (4.58–5.01 ppm) due to the mono-substi-
tuted Cp ring in compounds (8–12). In the 77Se
NMR spectra, diferrocenoyl selenide (9) shows a signal
at 763 ppm whereas diferrocenoyl diselenide (8) shows
a signal at 581 ppm. A downfield shift for the selenide
(9) as compared to the diselenide (8) is in contrast with
the diaryl selenides where generally the reverse trends
in 77Se NMR chemical shifts were found [11c,16].
The downfield shift of diferrocenoyl selenide (9) may
be due to the presence of two electron withdrawing
>C‚O groups (both groups are bonded to a single
selenium). However, the chemical shift of 9 is in close
agreement with those of the reported diacyl selenides
(765 38 ppm) [8a]. The 77Se chemical shift for diferr-
ocenoyl diselenide (581 ppm) is significantly upfield
shifted compared to the corresponding value reported
for dibenzoyl diselenide (615 ppm), bis(4-chloro-
benzoyl) diselenide (621 ppm), bis(2-methoxybenzoyl)
diselenide (615 ppm), bis(phenylacetyl) diselenide
(644 ppm) and bis(2-methoxybenzoyl) diselenide
(599 ppm) [7c]. The upfield shift of 8 may be due to
the more electron donating nature of the ferrocenoyl
group as compared to the phenyl substituents. Ferroce-
noyl selenol esters (10–12) show 77Se NMR chemical
shifts at 502, 405 and 628 ppm, respectively. These val-
ues are upfield shifted as compared to diferrocenoyl
selenide (9).
In the IR spectra, the mC‚O vibration for diferrocenyl
diselenide (8), diferrocenoyl selenide (9) and ferrocenoyl
selenol esters (10–12) are found in the range of 1670–
1716 cmꢀ1 and are shifted to higher frequency range
17–63 cmꢀ1 as compared to the parent compound 13
(mC‚O = 1653 cmꢀ1).
2.3. Electrospray mass (ES-MS) spectrometry study
The electrospray mass of 8, 9 and 11 show the corre-
sponding molecular ion peaks centered at m/z = 585.8,
505.9 and 454.0, respectively. In ES-MS of 8, 9 and 11
a peak at m/z = 213 with 100% intensity was observed;
this corresponds to the ferrocenoyl fragment [Fe(g5-
C5H5)(g5-C5H4C‚O)]+ and suggests that its formation
is easily possible under electrospray mass spectrometry
conditions.
Fig. 1. Cyclic voltammogram of diferrocenoyl diselenide (8).
Table 1
E1/2 and 77Se NMR chemical shifts of ferrocenoyl selenides
Compounds
E1/2 (mV)
77Se NMR (ppm)
8
9
413
374
367
359
380
284
581
763
502
405
628
–
2.4. Electrochemical studies
10
11
12
13
The redox properties of diferrocenoyl diselenide (8),
diferrocenoyl selenide (9), ferrocenoyl selenol esters

S. Kumar et al. / Journal of Organometallic Chemistry 689 (2004) 3046–3055
3049
compared to (FcSe)2 and FcSenBu may be due to the
presence of a >C‚O group between selenium and the
Cp ring.
The initial reduction rates for previously reported
diphenyl-, diferrocenyl- and dinaphthyl diselenides were
also measured out under similar conditions to compare
their catalytic activities with diferrocenoyl diselenide (8),
diferrocenoyl selenide (9) and ferrocenoyl selenol esters
(10–12). It is interesting to note that diselenide (8)
[65.53 4.45 lM minꢀ1] was found to be a ꢁ2.5 and
ꢁ2 times more efficient catalyst than diphenyl diselenide
[23.87 1.08 lM minꢀ1] and diferrocenyl diselenide
[34.01 0.39 lM minꢀ1], respectively, and also better
than dinaphthyl diselenide [53.07 5.39 lM minꢀ1] in
the reduction of H2O2 with PhSH as a co-substrate
[15]. The peroxidase-like activity of 8 indicates that dia-
cyl diselenides can act as catalysts in the thiol assay to
decompose the hydrogen peroxide in the same way as
more commonly studied diaryl and dialkyl diselenides.
Surprisingly diferrocenoyl selenide (9) and ferrocenoyl
selenol esters (10–12) did not show any activity in the
thiol assay even after 2- to 4-fold increase in the concen-
tration of the catalyst. Engman et al. [10] have demon-
strated that and selenol esters and a-(arylselenenyl)
ketones (1–7) convert the H2O2 into H2O at the expense
of glutathione and thus can act as mimics of the GPx en-
zyme. The rapid cleavage of the carbon–selenium bond
of selenol esters (1–2) and a-(arylselenenyl) ketones (3–
7) takes place by glutathione and give the catalytic reac-
tive intermediates [benzene selenolate, benzene selenenic
acid and S-(phenylselenenyl) glutathione] (Scheme 2).
Thus facile cleavage of the carbon–selenium [–C(O)–
SeR] bond is responsible for the GPx-like activity of
selenol esters (1–2) [10]. To understand the poor activity
of the ferrocenoyl selenol esters (10–12), the reaction of
12 with benzene thiol was carried out in methanol and
0.1 M phosphate buffer solution. No formation of the
expected benzene selenolate (based on the formation
of its oxidized product; diphenyl diselenide) and ferro-
cenecarboxaldehyde was observed even after 1 h as
monitored by TLC (Scheme 3), and thus indicating no
cleavage of C(O)–SeR in ferrocenoyl selenol ester (12).
Concerning the reactions of ferrocenoyl selenol esters
(10–12) and a-(arylselenenyl) ketones (1–2) a note must
be added that in the two systems different thiols (ben-
zenethiol and glutathione) and different selenol esters
were used.
Establishing the correlation between 77Se NMR
chemical shifts and E1/2 is difficult, although it is notice-
able that the diferrocenoyl diselenide (8), which shows a
significantly upfield 77Se chemical shift (581 ppm), has
the highest E1/2 value in this series. Furthermore, the
77Se chemical shifts (ppm) and E1/2 are in the same order
for 10, 11 and 12. This relationship indicates that ferr-
ocenoyl derivatives with upfield chemical shifts are diffi-
cult to oxidize on the electrochemical scale and this is in
accordance with the report of Morley et al. [17]. A sec-
ond wave was not observed initially in the case of all the
compounds (8–12). To find the second wave, the cyclic
voltammograms of these compounds were recorded over
a much wider range. The results from additional exper-
iments suggest that there is a second feature in the cyclic
voltammograms of these compounds. However, this fea-
ture was not well defined and occurred at 1.60–1.90 V; it
was electrochemically irreversible, since there was no
corresponding reduction found. The additional feature
may be due to the selenium acting as redox centre.
2.5. Initial reduction rates (v0)
The catalytic activity of 8–12 was studied according
to the method reported by Tomoda et al. [19] using ben-
zene thiol (PhSH) as a glutathione alternative. The ini-
tial rates (v0) for the reduction of H2O2 (3.75 mM) by
benzene thiol (1 mM) in the presence of various catalysts
(0.1 mM) (Eq. (1)) were determined in methanol med-
ium by monitoring the UV absorption at 305 nm due
to the formation of diphenyl disulfide (Fig. 2).
Catalyst
2PhSH þ H2O2 ! PhS–SPh þ 2H2O
ð1Þ
0.15
0.10
0.05
0.00
2.6. Crystallographic studies
2.6.1. Crystal structure of 8
A perspective view of diferrocenoyl diselenide (8) is
shown in Fig. 2, and the corresponding bond lengths
and angles are listed in Table 2. The coordination geom-
etry around the selenium atom is T-shaped where each
selenium is bonded to a selenium, a carbon and an oxy-
0
50
100
150
200
Time (s)
˚
gen atom. The Se–Se distance of 2.282(7) A relates well
to the corresponding values reported for diaryl disele-
Fig. 2. A plot of absorbance at 305 nm vs. time due to formation of
diphenyl disulfide.
˚
nides, which range from 2.29 to 2.39 A [11a]. This value

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S. Kumar et al. / Journal of Organometallic Chemistry 689 (2004) 3046–3055
Ph Se
PhSeSePh
O
O
GSH
Se
+
GSSePh
R
Ph
R
O
G S
SG
+
Ph Se
R
O
GSH
GSH
PhSe SePh
O
PhSe
R
1-2
O
SeR
R2Se2
+
Ph
Ph
CH3
3-7
Scheme 2. GPx activity of a-(arylselenol) ketones (1–7).
O
O
SeR
H
PhSH
Fe
Fe
+
R2Se2
10 R = 2-methylnaphthyl
11 R = 2,6-dimethyl-4-tert-butylphenyl
12 R = phenyl
Scheme 3. Reaction of selenol esters (10–12) with benzene thiol.
which are significantly shorter than the sum of their
˚
van der Waals radii (3.40 A) [20]. These values are
slightly longer than the corresponding mean value re-
ported for bis(2-methoxybenzoyl) diselenide (3.138(5)
Table 2
˚
Significant bond lengths (A) and angles (ꢁ) for 8 and 10
Compound (8)
Se(1)–Se(2)
C(11)–Se(1)
2.282(7) C(11A)–C(10A)
1.970(5) Se(2)ꢂ ꢂ ꢂO(2)
1.455(6)
2.780(4)
3.199(4)
93.6(16)
36.6(3)
˚
A) [7c]. These distances are also longer than the 1,4
C(11)–O(1)
C(11)–C(10)
1.182(6) Se(2)ꢂ ꢂ ꢂO(1)
intramolecular distance between selenium and the oxy-
gen of
1.465(6) O(1)ꢂ ꢂ ꢂSe(2)–C(11A)
2.789(9) Se(2)ꢂ ꢂ ꢂO(2)–C(11A)
3.198(4) C(11)–Se(1)–Se(2)
a methoxy group in (R,R)-bis{2-[1-(hyd-
˚
Se(1)ꢂ ꢂ ꢂO(1)
roxyl)ethyl]-6-methoxyphenyl}diselenide (2.977 A) [21]
and the distance between Se and O in selenazafurin
Se(1)ꢂ ꢂ ꢂO(2)
98.4(13)
O(1)ꢂ ꢂ ꢂSe(1)–C(11)
O(2)ꢂ ꢂ ꢂSe(1)–C(11A)
37.7(2)
94.9(13)
C(11)–Se–Se–C(11A) ꢀ89.1(18)
˚
(3.012 A) [22] but smaller than that in 5-amino-
˚
selenazafurin (3.314(4) A) [23]. Intramolecular short dis-
Compound (10)
Se(1)–C(11)
Se(1)–C(12)
C(11)–O
tances between Se(1)ꢂ ꢂ ꢂO(1) and Se(2)ꢂ ꢂ ꢂO(2) are also
1.919(2) C(10)–C(11)
1.945(3) C(11)–Se–C(12)
1.203(3) Se(1)–C(11)–C(10)
1.462(3)
99.2(11)
113.3(18)
˚
found and these distances (2.789(9) and 2.780(4) A)
are significantly shorter than the distances between
Se(1)ꢂ ꢂ ꢂO(2) and Se(2)ꢂ ꢂ ꢂO(1). The short distances be-
tween Se(1)ꢂ ꢂ ꢂ O(1) and Se(2)ꢂ ꢂ ꢂO(2) may be due to
the geometrical arrangement of the –C(O)Se– group.
The most interesting feature of this structure is that
compound 8 crystallizes in a chiral space group Pna21
with an orthorhombic crystal system. Refinement of
the Flack enantiopole parameter [24] shows that
is also close to the mean value reported for the diacyl
diselenide, bis(2-methoxybenzoyl) diselenide (2.311(9)
˚
A) [7c] (see Fig. 3).
The intramolecular distances of Se(1)ꢂ ꢂ ꢂO(2) and
˚
Se(2)ꢂ ꢂ ꢂO(1) are 3.198(4) and 3.199(4) A, respectively,

S. Kumar et al. / Journal of Organometallic Chemistry 689 (2004) 3046–3055
3051
Fig. 3. Molecular structure of 8 (hydrogen atoms are removed for clarity).
compound (8) has crystallized in an enantiomerically
pure form. Diferrocenoyl diselenide (8) also shows opti-
cal activity in solution. The torsion angle [C(11)–Se(1)–
Se(2)–C(11A) = ꢀ89.1(18)o] is significantly less than the
corresponding value reported for bis(2-methoxybenzoyl)
diselenide [104.8 (2)o]. However, this value is well within
the range of those reported for diaryl diselenides
(87.5(0)–95.6(3)o) [11a]. The torsion angle in 8, C(11)–
Se(1)–Se(2)–C(11A) indicates the skew conformation.
This is in accordance with theoretical ab initio MO
and NBO (natural bond orbital) calculations on diacyl
dichalcogenides. Kato et al. [7c] have reported that the
skew conformation is more stable than the planar in
the case of the diselenide based on the 2-meth-
oxybenzoyl group.
In this molecule no intermolecular Oꢂ ꢂ ꢂH hydrogen
bonding was observed.
3. Experimental
3.1. General comments
All reactions were carried out under nitrogen or ar-
gon using standard vacuum-line techniques. Solvents
were purified by standard procedures [28] and were
freshly distilled prior to use. Ferrocene carboxylic acid
[12], bis(2-methylnaphthyl) diselenide [15], bis(2,6-di-
methyl-4-tert-butylphenyl) diselenide [11a] were pre-
pared by following the literature methods. Melting
points were recorded in capillary tubes and are uncor-
rected. The IR spectra were recorded as KBr pellets
Another feature in the structure is the existence of
Hꢂ ꢂ ꢂO‚C intermolecular hydrogen bonding (Fig. 4).
The intermolecular distance between carbonyl oxygen
1
on a Nicolet Impact 400 FTIR spectrometer. The H
NMR and 13C NMR spectra were obtained at 300
MHz in CDCl3 on a Varian VXR 300S spectrometer.
˚
and hydrogen [O(2)ꢂ ꢂ ꢂH–C(9b) = 2.552(8) A] relates
˚
well to the disulfide analogue of 8 (2.542 A) [25]. Inter-
1
molecular hydrogen bonding between the Cp hydrogens
and O/N atoms has been reported in the ferrocene car-
boxaldehyde derivative, 4Õ-formyl-4-biphenylferrocene
[26].
The H and 13C NMR chemical shifts are cited with re-
spect to SiMe4 as internal standard. The 77Se NMR
spectra were obtained at 95.35 MHz, respectively, in
CDCl3 on a Bruker AMX500 spectrometer using diphe-
nyl diselenide as external standard. The chemical shifts
are reported relative to dimethyl selenide (77Se) by
assuming that the resonance of the standard is at 461
ppm. Elemental analyses were performed on a Carlo–
Erba model 1106 elemental analyzer. Optical rotations
were measured by a JASCO Model DIP 370 digital
polarimeter. Electrospray mass spectra (ES-MS) were
performed at room temperature on a Q-Tof micro
(YA-105) mass spectrometer. The m/z values are quoted
with reference to isotopomers containing 80Se; calcu-
lated and observed isotope distribution patterns were
in good agreement. Cyclic voltammetry: CHI660 scan-
ning potentiostat; Pt working and auxiliary electrodes;
Ag/Ag+ (0.1M AgNO3 in CH3CN) as reference elec-
2.6.2. Crystal structure of 10
The perspective view of 10 is shown in Fig. 5. The sig-
nificant bond lengths and angles are listed in Table 3.
The compound crystallizes in the monoclinic crystal sys-
tem with 4 molecules per unit cell. The Se–C bond dis-
˚
tances [Se–C(11), 1.919(2); Se–C(12), 1.945(3) A] are
within the range of reported oxazolinylferrocenyl phenyl
selenide and oxazolinylphenyl benzyl selenide (1.906(4)
˚
and 1.928(4) A) [16,27]. The C(11)–O(1) distance
˚
(1.203(3) A) is shorter than the corresponding distance
of diferrocenoyl diselenide (10). The C(11)–Se–C(12)
bond angle [99.2(11)ꢁ] is comparable with reported dia-
ryl and ferrocenyl aryl selenides [100.2(12) and 96.2(2)ꢁ].

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S. Kumar et al. / Journal of Organometallic Chemistry 689 (2004) 3046–3055
Fig. 4. Packing diagram of 8 showing C–Hꢂ ꢂ ꢂO intermolecular hydrogen bonding.
trode; 0.1 M [NBu4][ClO4] in CH3CN as a supporting
electrolyte; scan rate 200 mVsꢀ1; under these conditions
[Fe(C5H5)2]/ [Fe(C5H5)2]+ has E1/2 = +0.60 mV.
were added to the reaction mixture. The reaction mix-
ture was stirred at 0 ꢁC for 2 h, then extracted with
CH2Cl2 and washed with 1% NaHSO3 and water.
Standard work-up gave the crude solid of 8. This was
purified by flash chromatography on silica gel with hex-
ane and ethyl acetate (2:1) to give 8 (0.18 g, 30%) as a
red solid.
3.2. Preparation of diferrocenoyl diselenide (8)
3.2.1. Method (A)
Grey selenium (0.8 g, 1 mmol) was added portion
wise to LiAlH4 (0.04 g, 1 mmol) in THF with stirring
under an argon atmosphere. Gas evolution occurred,
and the suspension turned dark brown-red. The LiA-
lHSeH thus formed was stirred for at least 30 min. Ferr-
ocenoyl chloride (1 mmol), which was prepared by the
reaction of ferrocene carboxylic acid (0.23 g, 1 mmol)
and oxalyl chloride (0.9 mL, 1 mmol) in situ, was added
to the solution of LiAlHSeH (1 mmol). The reaction
mixture was stirred at 0 ꢁC for 1 h. Iodine (0.13 g,
1.0 mmol) and KI (0.04 g, 0.2 mmol) in THF (15 mL)
3.2.2. Method (B)
Grey selenium (0.8 g, 1 mmol) was added portionwise
to 1.2 mL of Li(C2H5)3BH (1.2 mmol, 1 M solution in
THF) with stirring under an argon atmosphere. Gas
evolution occurred, and the suspension turned dark
brown-red. The Li2Se2 thus formed was stirred for at
least 30 min. Ferrocenoyl chloride (1 mmol) in 5 mL
THF was added to the suspension of Li2Se2 at 0 ꢁC
and stirred for 1 h. The reaction mixture was stirred
for a further 3 h at room temperature. The reaction

S. Kumar et al. / Journal of Organometallic Chemistry 689 (2004) 3046–3055
3053
Fig. 5. Molecular structure of 10.
(t, 4H), 4.95 (t, 4H); ES-MS m/z 585.1 (M+, 25), 231.2
(30), 213 (100), 185 (10); IR (KBr) m 3112, 2940, 2848,
Table 3
Crystal data and structure refinement for 8 and 10
1683, 1440, 1242, 1045, 841, 775, 676, 499 cmꢀ1
.
Compound
8
10
Empirical formula
Formula weight
Crystal system
Space group
C
22H18 Fe2O2Se2
C22H18FeOSe
433.17
Monoclinic
P21/c
583.98
Orthorhombic
Pna21
3.3. Preparation of diferrocenoyl selenide (9)
˚
a (A)
12.3711(8)
12.4168(10)
13.1517(11)
90
10.8664(8)
14.2021(8)
12.2651(8)
90
Ferrocenoyl chloride (1 mmol) in 5 mL THF was
added to the suspension of LiAlHSeH at 0 ꢁC prepared
as in Section 3.2.1 and stirred for 1 h. The reaction mix-
ture was further stirred for 3 h at room temperature. The
standard work-up gave a red coloured solid. The crude
product was purified by column chromatography on sil-
ica gel by using hexane/ ethyl acetate (2:1) and gave the
two fractions (i) diferrocenoyl diselenide (0.01 g), (ii) dif-
errocenoyl selenide (9), which was crystallized from hex-
ane/CH2Cl2 to afford dark red plates. Yield: 0.46 g, 90%,
m.p. 174–176 ꢁC; Anal. Calc. for C22H18O2Fe2Se: C,
52.33; H, 3.59. Found: C, 52.23; H, 3.47; 1H NMR
(CDCl3) d 4.34 (s, 10H), 4.58 (t, 4H), 4.86 (t, 4H); 13C
NMR (CDCl3) d 69.74, 70.05, 70.83, 71.25, 72.90,
81.69, 187.98; ES-MS m/z 505.9 (M+, 10), 230.0 (30)
213 (100), 185 (10), 136 (20); IR (KBr) m 2927, 2847,
˚
b (A)
˚
c (A)
a (ꢁ)
b (ꢁ)
c (ꢁ)
90
90
108.972(8)
90
3
˚
V (A )
2020.2(3)
4
1.920
1790.0(2)
4
1.607
Z
Dcalc. (Mg/m3)
Abs. coeff. (mmꢀ1
Obs. refl. [I > 2r(I)]
Final R (F) [I > 2r(I)]a
wR (F2) [I > 2r(I)]
Absolute str. parameter
Data/restraints/parameters
Goodness-of-fit on F2
a
)
5.055
29188
2.882
27378
0.0280
0.0537
0.023(12)
3946/1/253
0.0325
0.0799
–
3781/0/227
1.018
0.895
P
P
Definitions: RðF oÞ ¼ kF o j ꢀ j F ck= j F o j and wRðF 2oÞ ¼
P
P
2
2
1=2
f
½wðF 2o ꢀ F c2Þ ꢃ= ½wðF 2c Þ g
:
1709, 1431, 1237, 1035, 831, 761, 487 cmꢀ1
.
mixture was poured in saturated aqueous solution of
brine and left overnight. The solidified product was sep-
arated by filtration and dried under vacuum. The crude
product was purified by flash chromatography on silica
gel with hexane and ethyl acetate (2:1) to give 8 as a red
solid. Compound 8 was recrystallized from hexane and
CH2Cl2 to afford red needles. Yield: 0.56 g (96%),
[a]D25 = ꢀ4.88 (0.037 c, CHCl3), m.p. 163–165 ꢁC; Anal.
Calc. for C22H18O2Fe2Se2: C, 45.26; H, 3.10. Found: C,
3.4. Preparation of 1-(2-methylnaphthyl) ferrocenoyl
selenide (10)
To a cold solution of bis(2-methylnaphthyl) disele-
nide [10d] (0.44 g, 1 mmol) in THF, Li(C2H5)3BH
(2.2 mL, 2.2 mmol, 1 M solution in THF) was added
portionwise under an argon atmosphere at 0 ꢁC and stir-
red for 1 h at this temperature. Ferrocenoyl chloride
(2 mmol) was added to the reaction mixture at 0 ꢁC.
1
44.97; H, 2.92; H NMR (CDCl3) d 4.39 (s, 10H), 4.60

3054
S. Kumar et al. / Journal of Organometallic Chemistry 689 (2004) 3046–3055
The reaction mixture was stirred for 1 h at 0 ꢁC and 3 h
at room temperature. The mixture was extracted with
diethyl ether and washed with saturated NaCl solution.
The organic layer was dried over sodium sulfate and
evaporated to dryness. The residue was purified by flash
chromatography on silica gel with CH2Cl2/ hexane (1:1).
The compound (10) was recrystallized from CH2Cl2/
hexane (1:2) to afford crystals of 10 as dark red plates.
Yield: 0.82 g (94%), m.p. 156–157 ꢁC; Anal. Calc. for
C22H18OFeSe: C, 61.01; H, 4.18. Found: C, 60.89; H,
the peroxidase activity, the rates were corrected for the
background reaction between H2O2 and PhSH. The ac-
tual concentration of PhSH in the kinetic apparatus was
measured from the 305 nm absorbance, and rates were
corrected for any variation in the concentration of
PhSH. The molar extinction coefficient of PhSSPh
(ꢀ1 = 1.24 · 103 Mꢀ1cmꢀ1) at the wavelength was much
larger than that of PhSH (e2 = 9 Mꢀ1cmꢀ1). The concen-
tration of diphenyl disulfide was, therefore, calculated
from the absorbance (A) according to the following
equation: C = A/(e1 ꢀ 2e2) ꢄ a/e1. The concentration of
the H2O2 stock solution was determined by permanga-
nate titration.
1
4.17; H NMR (CDCl3) d 2.71 (s, 3H), 4.33 (s, 5H),
4.62 (t 2H), 5.01 (t, 2H), 7.48–7.51 (m, 4H), 7.82 (t,
1H), 8.44 (d, 1H); IR (KBr) m 3104, 3039, 2920, 2848,
1670, 1433, 1236, 1032, 946, 782, 449 cmꢀ1
.
3.8. X-ray crystallography
3.5. Synthesis of 2-(2,6-Dimethyl-4-tert-butylphenyl)
ferrocenoyl selenide (11)
The diffraction measurements were performed on a
STOE (Darmstadt, Germany) IPDS imaging plate single
crystal diffractometer at room temperature with graph-
Compound 11 was prepared by a similar method as
described for 10 using bis(2,6-dimethyl-4-tert-butylphe-
nyl) diselenide [10c]. The standard work-up gave a red
oil. The crude product was purified by flash chroma-
tography by using hexane/ ethyl acetate (5:1) to afford
a red oil, which solidified on standing and was recrys-
tallized from hexane. Yield: 0.5 g (55%), m.p. 78–81
ꢁC; Anal. Calc. for C23H26OFeSe: C, 60.96; H, 5.78.
Found: C, 60.87; H, 5.66; 1H NMR (CDCl3) d 1.32
(s, 12H), 2.48 (s, 6H), 4.30 (s, 5H), 4.52 (t, 2H), 4.89
(t, 2H), 7.20 (s, 1H), 7.25 (s, 1H); 13C NMR (CDCl3)
d 24.82, 24.88, 29.78, 31.34, 34.52, 69.22, 70.18,
70.69, 72.00, 87.78, 81.78, 124.58, 125.16, 142.76,
152.35; ES-MS m/z 454.0 (M+, 20), 213 (100), 186
(90), 136 (10); IR (KBr) m 3106, 3068, 2830, 1680,
˚
ite-monochromated Mo K a radiation (k = 0.7107 A).
The structures were solved by direct methods and full-
matrix least-squares refinement on F2 (program
SHELXL-97) [29]. Hydrogen atoms were localized by
geometrical means. A riding model was chosen for
refinement. The isotropic thermal parameters of the H
atoms were fixed at 1.5 times (CH3 groups) or 1.2 times
U(eq) (Ar–H) of the corresponding C atom. Some de-
tails of the data collection and refinement are given in
Table 3.
Acknowledgements
1441, 1258, 949, 768, 499 cmꢀ1
.
This work was supported by the Department of Sci-
ence and Technology, New Delhi (DST grant to
H.B.S.) and Council of Scientific and Industrial Re-
search (CSIR), Government of India, New Delhi (Senior
Research Fellowship to S.K.).
3.6. Synthesis of phenyl ferrocenoyl selenide (12)
The compound was synthesized by the reduction of
diphenyl diselenide following the method as described
for 10. The crude product was purified by flash column
chromatography using hexane/CH2Cl2 (1:2). The com-
pound (12) was recrystallized from hexane/CH2Cl2 to
give red plates. Yield: 0.66 g (89%), m.p. 90–92 ꢁC; Anal.
Calc. for C17H14OFeSe: C, 55.33; H, 3.82. Found: C,
Appendix A. Supporting material
NMR and electrospray mass spectra of compounds 8–
12 and thiol peroxidase activity data of compound (8)
may be obtained from http://www.sciencedirect.com.
Crystallographic data for the structural analyses have
been deposited with the Cambridge Crystallographic
Data Centre; CCDC Nos. 238713 and 238714 for com-
pounds 8 and 10, respectively. Copies of this information
may be obtained free of the charge from The Director,
CCDC, 12 Union Road, Cambridge, CB2 1 EZ, UK
(fax: +/44-1223-336033; email: deposit@ccdc.cam.ac.uk
or http://www.ccd.cam.ac.uk). Supplementary data asso-
ciated with this article can be found, in the online version
at doi:10.1016/j.jorganchem.2004.06.054.
1
54.89; H, 3.65; H NMR (CDCl3) d 4.28 (5H, s), 4.53
(t, 2H), 4.86 (t, 2H), 7.38–7.40 (m, 3H), 7.58–7.60
(m,2H); IR (KBr) m 2933, 2848, 1716, 1440, 1236,
1045, 834, 769, 492 cmꢀ1
.
3.7. PhSH assay
The reactions of model compounds with benzenethiol
(PhSH) and H2O2 were studied by following the appear-
ance of the disulfide absorption at 305 nm, at 25 ꢁC.
Each initial velocity was measured at least 6 times and
calculated from the first 5–10% of the reaction. For

S. Kumar et al. / Journal of Organometallic Chemistry 689 (2004) 3046–3055
3055
(b) M. Koketsu, F. Nada, S. Hiramatsu, H. Ishihara, J. Chem.
Soc., Perkin Trans. 1 (2002) 737.
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