Direct C-C-coupling of ferrocenyl- and cymantrenyllithium with 5-(het)aryl-1,2,5-oxadiazolo[3,4-b]pyrazines

Article abstract of DOI:10.1007/s11172-011-0389-z

A direct C-C-coupling of ferrocenyl- and cymantrenyllithium with 5-(het)aryl-1,2,5- oxadiazolo[3,4-b]pyrazines was accomplished. Main characteristics of the SN H-reaction products were obtained, as well as crystallographic data on the spatial structure of oxadiazolopyr-azinylferrocenes and -cymantrenes synthesized.

Full text of DOI:10.1007/s11172-011-0389-z

Russian Chemical Bulletin, International Edition, Vol. 60, No. 12, pp. 2531—2535, December, 2011
2531
Direct C—Cꢀcoupling of ferrocenylꢀ and cymantrenyllithium
with 5ꢀ(het)arylꢀ1,2,5ꢀoxadiazolo[3,4ꢀb]pyrazines*
I. A. Utepova,a A. A. Musikhina,a Yu. A. Kvashnin,b M. A. Shcherbakova,a
P. O. Serebrennikova,a G. L. Rusinov,b and O. N. Chupakhina,b
aUral Federal University,
19 ul. Mira, 620002 Ekaterinburg, Russian Federation.
Fax: +7 (343) 374 0458. Eꢀmail: utepova@mail.ustu.ru
bI. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences,
22 ul. S. Kovalevskoi, 620041 Ekaterinburg, Russian Federation.
Fax: +7 (343) 374 1189. Eꢀmail: chupakhin@ios.uran.ru
A direct C—Cꢀcoupling of ferrocenylꢀ and cymantrenyllithium with 5ꢀ(het)arylꢀ1,2,5ꢀ
oxadiazolo[3,4ꢀb]pyrazines was accomplished. Main characteristics of the SNHꢀreaction prodꢀ
ucts were obtained, as well as crystallographic data on the spatial structure of oxadiazolopyrꢀ
azinylferrocenes and ꢀcymantrenes synthesized.
Key words: ferrocenyllithium, cymantrenyllithium, 5ꢀ(het)arylꢀ1,2,5ꢀoxadiazolo[3,4ꢀb]ꢀ
H
pyrazines,  ꢀadducts, nucleophilic substitution of hydrogen.
Metallocene heterocyclic derivatives are usually obꢀ
tained by two synthetic approaches.1 Hetarylmetallocenes
can be constructed either by buildingꢀup a heterocyclic
subunit based on the groups preꢀintroduced into the subꢀ
strate (metallocene) structure, or as a result of the direct
coupling of functional blocks (metallocene and heteroꢀ
cycle) with each other. The use of the former method is
limited since it is laborꢀconsuming and in some case beꢀ
cause of impossibility to obtain metallocene synthons.
Therefore, a direct C—Cꢀcoupling of metallocenes with
heterocyclic derivatives is recently under intensive deveꢀ
lopment. Different versions of crossꢀcoupling reactions are
most frequently used as such synthetic approaches.1 In
addition, a synthetic strategy of the oxidative nucleophilic
substitution of hydrogen (SNH(AO)) can be also successꢀ
fully used for the preparation of ferrocene1,2 and cymanꢀ
trene3 heterocyclic derivatives.
According to the common knowledge, oxidative nucleoꢀ
philic substitution of hydrogen of the type SNH(AO) occurs
in two steps (Scheme 1).11 In the first step, a nucleophilic
fragment adds to the substrates 1 bearing electronꢀwithꢀ
drawing substituents to form Hꢀadducts 2. In the second
step, aromatization of these intermediates to the corresponꢀ
ding SNHꢀproducts 3 occurs upon the action of oxidants.
Scheme 1
EWG is the electronꢀwithdrawing group, Nu is the nucleophile
Ferrocene4—7 and cymantrene8,9 heterocyclic derivaꢀ
tives possess a wide range of various applied properties.
Therefore, preparation of such compounds and studies of
their properties is a relevant synthetic problem.
Results and Discussion
In the present work, we studied a possibility of the use
of 5ꢀ(het)arylꢀ1,2,5ꢀoxadiazolo[3,4ꢀb]pyrazines as subꢀ
strates in the reaction of nucleophilic substitution of hyꢀ
drogen with ferrocenylꢀ and cymantrenyllithium. Furazanoꢀ
pyrazines and their derivatives manifest high activity in
the SNHꢀreactions with different nucleophilic agents.10
Earlier, we have accomplished a series of work devoted
to the studies of reactions of ferrocenyllithium with azines
and optimization of the reaction conditions (ratio of reꢀ
agents, temperature, solvent, etc.). It was found2 that the
transformation occurs according to the mechanism deꢀ
scribed above via formation of Hꢀadducts.
When ferrocenyllithium (4) (obtained by the reacꢀ
tion of bromoferrocene with BuLi in THF at 0 C) reactꢀ
ed with oxadiazolopyrazines 5a—c as electrophilic agents,
* Dedicated to Academician of the Russian Academy of Sciences
R. Z. Sagdeev on the occasion of his 70th birthday.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2482—2486, December, 2011.
1066ꢀ5285/11/6012ꢀ2531 © 2011 Springer Science+Business Media, Inc.

2532
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 12, December, 2011
Utepova et al.
the corresponding SNHꢀproducts 6a—c were successfully
obtained (Scheme 2). 5ꢀ(Het)arylꢀ1,2,5ꢀoxadiazoloꢀ
[3,4ꢀb]pyrazines 5a—c react with ferrocenyllithium (4) in
the ratio 1 : 1 in anhydrous THF at 0 C to initially form
the salt A1, which then upon the action of the air moisture
is spontaneously hydrolyzed to the adduct B1. The latter
upon the action of DDQ is oxidized to the substitution
products 6a—c. Oxidation of the Hꢀadducts B1 can ocꢀ
cur by exposure to air, as well. Note that the reaction
results in higher yields (by 15% on average) when DDQ
was used as an oxidant.
5ꢀ(Het)arylꢀ1,2,5ꢀoxadiazolo[3,4ꢀb]pyrazines 5a,b
also react with cymantrenyllithium (7), obtained by metꢀ
allation of cymantrene with BuLi in THF at –78 C. The
lithium derivative 7 readily reacts with azines 5a,b with
the formation of azinylcymantrenes 8a,b (Scheme 3). After
electrophilic agents were added to cymantrenyllithium at
–78 C, the reaction mixture was kept for 1.5 h at this
temperature, then the temperature was gradually raised to
ambient. Earlier,3 it has been shown that these transforꢀ
mations also proceeded in two steps according to the
mechanism given in Scheme 1. Oxidation of the Hꢀadꢀ
duct B2 takes place only in the presence of DDQ. If the
reaction mixture was exposed to air for a long time, adꢀ
ducts B2 are converted to a mixture of compounds of
unestablished structure.
8a,b were isolated by column chromatography on Al2O3
and SiO2, respectively. The products synthesized are deeply
colored crystalline compounds, ranging from dark
green to dark blue in the case of hetarylferrocenes 6a—c
and being dark red in color in the case of hetarylcymanꢀ
trenes 8a,b.
The 1H NMR spectra of products 6a—c exhibit signals
for the protons of the monosubstituted ferrocene system as
a single fiveꢀproton singlet for the unsubstituted cycloꢀ
pentadienyl ferrocene fragment ( 4.1—4.2) and two tripꢀ
lets with the intensities for two protons for the monosubꢀ
stituted cyclopentadienyl fragment ( 4.4—4.7), as well as
signals for the corresponding aryl substituents. The IR
spectrum of compound 6b exhibits an absorption band
related to the stretching vibrations of the NO2 group in
the region 1530 cm–1. Mass spectra contain peaks of moꢀ
lecular ions.
1
The H NMR spectra of compounds 8a,b exhibit sigꢀ
nals characteristic of the protons of monosubstituted
cymantrene cyclopentadienyl ring as two multiplets with
intensity of two proton ( 4.8—5.2), as well as signals for
the protons of aryl substituents. Mass spectra contain peaks
of molecular ions. In the IR spectra of these compounds,
absorption bands characteristic of the corresponding viꢀ
brations of the CO group of cymantrene are observed
(1900—2020 cm–1).
Compounds 6a—c were obtained in 60—75% yields,
compounds 8a,b, in 50—60% yields. Products 6a—c and
Molecular and crystal structure of derivatives 6 and 8
were studied by Xꢀray crystallography (Figs 1 and 2).
Scheme 2
R = Ph (a), 3ꢀNO2C6H4 (b), 3ꢀthienyl (c)
Scheme 3
R = Ph (a), 3ꢀNO2C6H4 (b)

SNH reactions in furazanopyrazines
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 12, December, 2011
2533
relatively to Me4Si. IR spectra were recorded on a Bruker Alpha
IR Fourierꢀspectrometer with an FTIR accessory. Mass spectra
were recorded on a Bruker Daltonics MicrOTOFꢀQ II mass
spectrometer equipped with a source of electroꢀspray ionization,
sixꢀway stopcock, and a kd Scientific direct injection facility.
Elemental analysis was performed on a Perkin—Elmer 2400ꢀII
instrument. Melting points were measured on a Boetius apparaꢀ
tus. TLC was performed on Alugram Sil G/UV254 or Poligram
Alox N/UVꢀ254 plates, using visualization with the UV light.
Solvents were purified and dried according to the standard
procedures. Silica gel and alumina (for column chromatograꢀ
phy), ferrocene, cymantrene, and THF were purchased from
Aldrich. Other reagents and solvents are of homeꢀcountry made.
Bromoferrocene,12 5ꢀphenylꢀ1,2,5ꢀoxadiazolo[3,4ꢀb]pyrꢀ
azine (5a),13 5ꢀ(3ꢀnitrophenyl)ꢀ1,2,5ꢀoxadiazolo[3,4ꢀb]pyrazine
(5b),13 and 5ꢀ(thienꢀ3ꢀyl)ꢀ1,2,5ꢀoxadiazolo[3,4ꢀb]pyrazine (5c)10
were obtained according to the known procedures.
C(9)
C(8)
C(10)
C(1)
C(7)
C(14)
C(15)
C(4)
C(11)
C(13)
C(5)
N(4)
C(3)
C(12)
N(3)
O(1)
C(6)
N(1)
C(16)
Fe(1)
C(19)
C(2)
C(18)
N(2)
C(17)
Synthesis of compounds 6a—c (general procedure). A 1.6 M
solution of BuLi in hexane (0.63 mL, 1 mmol) was added to
a solution of bromoferrocene (1 mmol) in THF (5 mL) at 0 C
under argon, and the mixture was stirred for 10—15 min, folꢀ
lowed by addition of a solution of furazanopyrazine 5a—c
(1 mmol) in THF (5 mL). The reaction mixture was stirred for
30 min at 0 C, then for another 1 h at room temperature. Then,
a solution of DDQ (1 mmol) in THF (5 mL) was added. A susꢀ
pension that formed was immediately filtered through a layer
of Al2O3. The solution was concentrated at reduced pressure.
The thus obtained residue was subjected to preparative column
chromatography on Al2O3. The fraction that collected was conꢀ
centrated.
1ꢀ(5ꢀPhenylꢀ1,2,5ꢀoxadiazolo[3,4ꢀb]pyrazinꢀ6ꢀyl)ferrocene
(6a). Dark blue crystals. The yield was 0.29 g (75%), m.p. 226 C,
Rf 0.4 (hexane—ethyl acetate, 8 : 2). 1H NMR (DMSOꢀd6—CCl4),
: 4.13 (m, 5 H, CpH); 4.42, 4.60 (both m, 2 H each, C5H4); 7.58
(m, 5 H, Ph). IR, /cm–1: 1450, 1356, 1014. MS (EI, 70 eV),
m/z: 383 [M + H]+. Found (%): C, 62.57; H, 3.31; N, 14.46.
C20H14FeN4O. Calculated (%): C, 62.83; H, 3.66; N, 14.66.
1ꢀ[5ꢀ(3ꢀNitrophenyl)ꢀ1,2,5ꢀoxadiazolo[3,4ꢀb]pyrazinꢀ6ꢀyl]ꢀ
ferrocene (6b). Dark blue crystals. The yield was 0.30 g (70%),
m.p. 296 C, Rf 0.4 (hexane—ethyl acetate, 7 : 3). 1H NMR
(DMSOꢀd6—CCl4), : 4.19 (m, 5 H, CpH); 4.40, 4.62 (both m,
Fig. 1. Molecular structure of compound 6a in thermal ellipsoids
of 50% probability.
C(9)
C(10)
C(8)
C(5)
C(2)
C(7)
N(4)
C(6)
N(2)
C(3)
C(12)
C(11)
O(4)
C(1)
C(13)
C(15)
C(4)
N(1)
C(14)
N(3)
O(1)
C(17)
C(16)
C(18)
O(3)
2 H each, C5H4); 7.87 (m, 1 H, HAr); 8.04 (d, 1 H, HAr
,
:
3J = 8.0 Hz); 8.48, 8.54 (both m, 1 H each, HAr). IR, /cm–1
O(2)
1530, 1454, 1327, 1251. MS (EI, 70 eV), m/z: 428 [M + H]+.
Found (%): C, 56.27; H, 3.11; N, 16.62. C20H13FeN5O3. Calcuꢀ
lated (%): C, 56.21; H, 3.04; N, 16.39.
Fig. 2. Molecular structure of compound 8a in thermal ellipsoids
of 50% probability.
1ꢀ[5ꢀ(Thienꢀ3ꢀyl)ꢀ1,2,5ꢀoxadiazolo[3,4ꢀb]pyrazinꢀ6ꢀyl]ꢀ
ferrocene (6c). Dark green crystals. The yield was 0.23 g (60%),
1
In conclusion, the studies accomplished resulted in
the direct C—Cꢀcoupling of ferrocenylꢀ and cymantreꢀ
nyllithium with 5ꢀ(het)arylꢀ1,2,5ꢀoxadiazolo[3,4ꢀb]pyrꢀ
azines. Main characteristics were obtained for the proꢀ
ducts of the SNHꢀreaction, as well as crystallographic data
on the spatial structure of the synthesized oxadiazolopyrꢀ
azinylferrocenes and ꢀcymantrenes.
m.p. 220 C, Rf 0.45 (hexane—ethyl acetate, 9 : 1). H NMR
(DMSOꢀd6—CCl4), : 4.14 (m, 5 H, CpH); 4.59, 4.64 (both m,
2 H each, C5H4); 7.30 (d, 1 H, C4H3S, 3J = 4.8 Hz); 7.62 (m, 1 H,
C4H3S); 7.88 (d, 1 H, C4H3S, 3J = 2.5 Hz). IR, /cm–1
:
3095, 1633, 1495, 1446, 1381, 1236. MS (EI, 70 eV), m/z:
389 [M + H]+. Found (%): C, 55.53; H, 3.21; N, 14.51.
C18H12FeN4OS. Calculated (%): C, 55.67; H, 3.09; N, 14.43.
Synthesis of compounds 8a,b (general procedure). A 1.6 M
solution of BuLi in hexane (0.63 mL, 1 mmol) was added to
a solution of cymantrene (1.2 mmol) in THF (5 mL) at –78 C
under argon. After the mixture was stirred for 30 min, a solution
of furazanopyrazine 5a,b (1 mmol) in THF (5 mL) was added,
followed by stirring first for 1.5 h at –78 C and then for another
Experimental
1
H NMR spectra (400 MHz) were recorded on a Brukerꢀ400
AVANCE II spectrometer, chemical shifts are given in the  scale

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Utepova et al.
1 h at room temperature. The reaction mixture was workedꢀup
with a solution of DDQ in THF (7 mL), immediately filtered
through a layer of Al2O3, and concentrated at reduced pressure.
The thus obtained residue was subjected to preparative column
chromatography on SiO2. The fraction that collected was
concentrated.
1ꢀ(5ꢀPhenylꢀ1,2,5ꢀoxadiazolo[3,4ꢀb]pyrazinꢀ6ꢀyl)cymantꢀ
rene (8a). Dark red crystals. The yield was 0.22 g (55%), m.p.
188 C, Rf 0.5 (CH2Cl2). 1H NMR (CDCl3), : 4.80, 5.14
(both m, 2 H each, C5H4); 7.58 (m, 5 H, Ph). IR, /cm–1: 3090,
2025, 1935, 1432, 1259, 980. MS (EI, 70 eV), m/z: 401 [M + H]+.
Found (%): C, 53.97; H, 2.31; N, 14.06. C18H9MnN4O4. Calcuꢀ
lated (%): C, 54.00; H, 2.25; N, 14.00.
1ꢀ[5ꢀ(3ꢀNitrophenyl)ꢀ1,2,5ꢀoxadiazolo[3,4ꢀb]pyrazinꢀ6ꢀ
yl]cymantrene (8b). Dark red crystals. The yield was 0.27 g (60%),
1
m.p. 184 C, Rf 0.5 (CH2Cl2). H NMR (CDCl3), : 4.87, 5.16
(both m, 2 H each, C5H4); 7.83 (t, 1 H, HAr, 3J = 7.3 Hz); 7.99
(d, 1 H, HAr, 3J = 7.0 Hz); 8.48 (d, 1 H, HAr, 3J = 6.0 Hz); 8.55
(s, 1 H, HAr). IR, /cm–1: 2017, 1921, 1527, 1350. MS (EI, 70 eV),
m/z: 446 [M + H]+. Found (%): C, 48.27; H, 1.31; N, 15.66.
C18H8MnN5O6. Calculated (%): C, 48.54; H, 1.80; N, 15.73.
Xꢀray diffraction studies. For Xꢀray crystallography, the dark
blue plates of crystals 6a were obtained by slow concentration of
their solution in CH2Cl2, whereas the red prisms of crystals 8a by
slow concentration of their solution in Et2O. The experimental
set of reflections was obtained on a Xcalibur 3 ((Mo) diffractoꢀ
meter, graphite monochromator, T = 295(2) K, ꢀscanning, the
step of scanning 1). The structures were solved by the direct
method using the SHELXS97 program14 and refined using the
SHELXL97 program by the least squares method in the anisoꢀ
tropic (isotropic for the H atoms) fullꢀmatrix approximation
on F2. The hydrogen atoms were placed in the geometrically
calculated positions and refined in the isotropic approximation
with the dependent thermal parameters.15 The bond angles and
bond distances are close to the standard values. The oxadiazoloꢀ
pyrazine fragment is planar, with deviation of the atoms from
the meanꢀsquare plane being <0.025 Å. The plane of the phenyl
ring in compound 6a is turned with respect to the plane of the
oxadiazolopyrazine fragment by 84.5, in compound 8a, by 60.
The results of the Xꢀray diffraction studies of compounds 6a and
8a are given in Table 1.
Table 1. Principal crystallographic data and parameters of the
Xꢀray diffraction experiments for compounds 6a and 8a
Parameter
6a
8a
Formula
C20H14FeN4O C18H9MnN4O4
М
/Å
Crystal system
Space group
382.20
0.71073
Monoclinic
P21/c
400.23
0.71073
Tricl–inic
P1
a/Å
b/Å
c/Å
/deg
11.2860(13)
8.1939(9)
17.791(2)
90.00
95.830(9)
90.00
1636.7(3)
4
1.551
9.2253(4)
10.0114(4)
10.2396(4)
84.038(3)
88.523(3)
63.796(4)
843.71(6)
2
/deg
/deg
V/Å3
Z
dcalc/g cm–3
1.575
0.816
/mm–1
0.938
F(000)
784
404
The results of the Xꢀray diffraction studies were deposited
with the Cambrige Structural Database (CCDC 856598 (6a) and
CCDC 856599 (8a)). These materials are available for no charge
at www.ccdc.cam.ac.uk/data_request/cif.
Crystal size/mm
Region of scanning,
2/deg
0.25×0.16×0.02 0.22×0.14×0.03
2.74—33.51
2.87—30.50
Completeness on 2max (%)
Ranges of indices
of reflections
88.7
97.9
–17 < h < 16,
–12 < k < 10,
–27 < l < 12
15684
–13 < h < 13,
–14 < k < 14,
–14 < l < 11
12305
The authors are grateful to P. A. Slepukhin for carrying
out the Xꢀray diffraction analysis.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 10ꢀ03ꢀ00756ꢀa)
and the Council on Grants at the President of the Rusꢀ
sian Federation (Program of State Support for Young
Scientists and Leading Scientific Schools, Grants
MKꢀ1901.2011.3 and NShꢀ65261.2010.3).
Total number
of reflections
Number of independent
reflections
5751
5062
Rint
0.0271
2744
0.0190
3494
Number of reflections
with I > 2(I)
Number of refined
parameters
235
244
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Correction on absorption
Transmission (max/min)
GOOF (on F2)
RꢀFactors (on reflections
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R1
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0.0503
0.0981
wR2
max/min/e Å–3
0.414/–0.377
0.375/–0.319

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Received August 29, 2011;
in revised form November 24, 2011