Synthesis and characterization of homoannularly disubstituted and heteroannularly trisubstituted ferrocene derivatives by arsenic and silicon or by arsenic and tin

Article abstract of DOI:10.1021/om7004468

The ferrocene derivatives (5-10) homoannularly disubstituted and heteroannularly trisubstituted by two different kinds of main-group elements, i.e., arsenic (As) and silicon (Si) or tin (Sn), were synthesized from N,N-dimethylaminomethylferrocene (1) and

Full text of DOI:10.1021/om7004468

Organometallics 2007, 26, 6219-6224
6219
Synthesis and Characterization of Homoannularly Disubstituted and
Heteroannularly Trisubstituted Ferrocene Derivatives by Arsenic
and Silicon or by Arsenic and Tin
Hongguang Du,† Ki Chul Park,‡ Feng Wang,*,§ Shuming Wang,† Qun Liu, Shiwei Zhang,
Yuli Huang,† and Shujian Shi†
College of Science, Beijing UniVersity of Chemical Technology,
Beijing 100029, People’s Republic of China, Faculty of Engineering, Shinshu UniVersity, Wakasato 4-17-1,
Nagano 380-8553, Japan, College of Materials Science and Engineering, Beijing UniVersity of Chemical
Technology, Beijing 100029, People’s Republic of China, and Institute of Physical Chemistry, Peking
UniVersity, Beijing 100871, People’s Republic of China
ReceiVed May 5, 2007
The ferrocene derivatives (5-10) homoannularly disubstituted and heteroannularly trisubstituted by
two different kinds of main-group elements, i.e., arsenic (As) and silicon (Si) or tin (Sn), were synthesized
from N,N-dimethylaminomethylferrocene (1) and its diphenylarsino derivative 2 through mono- or
dilithiation, followed by substitution with the organo-substituted chlorides RmMCln [R ) alkyl, (m, n) )
(2, 2) or (3, 1)] of main-group elements M ) As, Si, or Sn. The dimethylaminomethyl (-CH2NMe2)
group of the starting compounds facilitates lithiation of the cyclopentadienyl (Cp) ring and introduces
lithium into the ortho-position of the -CH2NMe2 groups by the directing functionality. The efficiency
of the subsequent substitution reaction with the organo-substituted chlorides RmMCln is influenced not
only by their reactivity but also by the spatial factors of the main-group elements and the ferrocene
derivative molecules to be reacted. All products 5-10 were identified by elemental analysis, proton
nuclear magnetic resonance (1H NMR) spectroscopy, and mass spectrometry (MS). Furthermore, the
X-ray crystal structure of 5 was determined. The application of 5, 6, and 10 to fungicides for crop plant
diseases was examined. The results of the percent inhibition test for fungal growth have indicated that
the derivative 10 has high fungicidal activity for early tomato blight.
disubstitued ferrocenes.13-17 However, there are only a few
research works on the ferrocene derivatives substitued by two
different kinds of main-group elements. For example, Ahn et
al. have previously synthesized the ferrocene derivatives ho-
moannularly disubstituted by silicon (Si) and phosphorus (P)
or Si and sulfur (S), which are introduced into the 2,5-positions
of the cyclopentadienyl (Cp) ring substituted by the ortho-
directing groups.18 Iftime et al. have synthesized the ferrocene
derivatives heteroannularly disubstituted by Si and Sn.19 Inves-
tigations in the field of the ferrocene derivatives of arsenic (As)
have been rare since the research by Sollot et al.20 and Bishop
Introduction
Ferrocene and ferrocene derivatives are widely used in various
areas1-4 such as asymmetric catalysis, photochemistry, and
electrochemistry, due to their unique steric structures and a
variety of chemical and physical properties. Therefore, the
derivatization of ferrocene has become a significant branch of
ferrocene chemistry. To date, many ferrocene derivatives
containing main-group elements have been synthesized and
characterized, which are of great interest not only in ferrocene
chemistry but also in the chemistry of organometallics and main-
group elements. Most of the previous reports about the synthesis
of ferrocenyl organometallics and ferrocene derivatives substi-
tuted by main-group elements refer to mono-5-12 and 1,1′-
(9) Herberhold, M.; Steffl, U.; Milius, W.; Wrackmeyer, B. J. Organomet.
Chem. 1997, 533, 109.
* To whom correspondence should be addressed. E-mail: wangf@
mail.buct.edu.cn.
(10) Herberhold, M.; Steffl, U.; Milius, W.; Wrackmeyer, B. Chem.-
Eur. J. 1998, 4, 1027.
† College of Science, Beijing University of Chemical Technology.
‡ Shinshu University.
(11) Dong, T. Y.; Hwang, M. Y.; Wen, Y. S.; Hwang, W. S. J.
Organomet. Chem. 1990, 391, 377.
(12) Jakle, F.; Rulkens, R.; Zech, G.; Foucher, D. A.; Lough, A. J.;
Manners, I. Chem.-Eur. J. 1998, 4, 2117.
(13) Herberhold, M.; Steffl, U.; Milius, W.; Wrackmeyer, B. Angew.
Chem., Int. Ed. Engl. 1996, 108, 1927. Herberhold, M.; Steffl, U.; Milius,
W.; Wrackmeyer, B. Angew. Chem., Int. Ed. Engl. 1996, 35, 1803.
(14) Herberhold, M.; Milius, W.; Steffl, U.; Vitzithum, K.; Wrackmeyer,
B.; Herber, R. H.; Fontani, M.; Zanello, P. Eur. J. Inorg. Chem. 1999, 145.
(15) Wright, M. E. Organometallics 1990, 9, 853.
§ College of Materials Science and Engineering, Beijing University of
Chemical Technology.
Peking University.
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Chem. 1998, 42, 291.
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Organometallics 1996, 15, 4808.
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10.1021/om7004468 CCC: $37.00 © 2007 American Chemical Society
Publication on Web 11/03/2007

6220 Organometallics, Vol. 26, No. 25, 2007
Du et al.
et al.21 Furthermore, there is no report about the synthesis and
characterization of disubstituted ferrocene derivatives by As and
other main-group elements.
activities of ferrocene-based metal complexes is involved. Haque
et al. have reported that the ferrocene derivative manganese
complex shows the maximum antibacterial and antifungal
activities compared with other cobalt, nickel, copper, and zinc
complexes.38 Different from the research on transition-metal
complexes of ferrocene derivatives, we have tried to examine
the applicability of the ferrocene derivatives containing two
main-group elements of As, Si, and Sn to antifungal agents,
because organosilicon, organoarsenic, and organotin compounds
exhibit bioactivity such as antimicrobial and fungicidal effects
at a certain level. In this work, the fungicidal activity of 5, 6,
and 10 for crop plants was examined against fusarium head
blight of wheat, early blight of tomato, wilt disease of cotton,
ring-rot disease of apple, and brown blotch disease of peanut.
In recent years, we have investigated the ferrocene derivatives
substituted by two different main-group elements in the presence
of a strongly ortho-directing N,N-dimethylaminomethyl (-CH2-
NMe2) functionality. Here we report the synthesis of the
ferrocene derivatives (5 and 6) homoannularly disubstituted by
As and Si or by As and tin (Sn), as well as the dimethylsilicon-
and the dibutyltin-bridged bis(diphenylarsinoferrocene) deriva-
tives (7 and 8), and the heteroannularly 2,5,1′-trisubstituted
derivatives (9 and 10) of N,N-dimethylaminomethylferrocene
(1). Basically, the homoannularly disubstituted ferrocenes and
the bridged ferrocene derivatives were obtained by twice using
the well-established monosubstitution reaction of the lithium
ferrocenides prepared using n-buthyllithium (n-BuLi)22-24 with
organotin, organoarsenic, or organosilicon chlorides. Note that
organostannyl ferrocenes easily undergo a Sn-Li exchange
reaction by organolithium in relatively strong coordinating
solvents25 such as DME, THF, and Et2O, where a tin ate
complex, stabilized in the solvent, is proposed as an intermediate
for the exchange reaction. Tetraorganylsilanes also form an ate
complex with organolithium,26 which is likely to cause a
lowering of the yields of lithiation by unfavorable Si-Li
exchange reactions. As mentioned above, Iftime et al. have ably
introduced Bu3Sn- to the 1′-position of ferrocenecarbaldehydes
containing trimethylsilyl (Me3Si-) groups in the 2-position by
employing the temporary directing group lithium N-methylpip-
erazide, whose amine moiety forms a chelate complex with
organolithium reagents to lithiate selectively the 1′-position. This
work has tried to introduce Sn and As or Si and As into the
same Cp ring. To the best of our knowledge, there has been no
report about As-Li exchange reactions and the formation of
an arsenic ate complex. Thus, the possibility of the straightfor-
ward introduction of two main-group elements to the same Cp
ring was examined in the order of As and Sn and As and Si,
where the ortho-directing Me2NCH2- group would also con-
tribute to the selective lithiation of the Cp ring even in the
presence of another main-group element by its coordinating
ability. In the synthesis of the heteroannularly trisubstituted
derivatives, the dilithium ferrocenides obtained using n-BuLi
and N,N,N′N′-tetramethylethylenediamine (TMEDA)27 are used
in the heteroannular introduction of main-group elements. The
structures of all products 5-10 were characterized by elemental
Results and Discussion
Synthesis of the Ferrocene Derivatives 5-10 Containing
Arsenic and Silicon or Tin. The basic route for the synthesis
of ferrocenyl organometallics is the lithiation of ferrocene by
n-BuLi followed by the substitution reaction of the resulting
lithiated ferrocene with organometal chlorides.39-41 This is also
an important route for the introduction of main-group elements
into the Cp ring of ferrocenes. In this basic route, however,
there are problems: the reaction time of the lithiation is
relatively long, the reaction yield of the lithiated ferrocene with
the organo-substituted chlorides of main-group elements is low,
and the resulting ferrocene derivative is a mixture of mono-
substituted and disubstituted ferrocene. In contrast, the introduc-
tion of -CH2NMe2 groups into the Cp ring facilitates the
lithiation of ferrocenes to decrease the reaction time (ca. 1 h
with n-BuLi in diethyl ether).42 The directing -CH2NMe2
functionality of N,N-dimethylaminomethylferrocene (1) intro-
duces lithium into the ortho-position of the -CH2NMe2 groups.
The introduced lithium probably forms a chelation complex with
the amine nitrogen.42 The resulting 1-dimethylaminomethyl-2-
lithioferrocene undergoes substitution by the organo-substituted
chlorides of main-group elements to provide the ferrocene
derivatives (e.g., compound 2) containing main-group elements
at the ortho-positions adjacent to the -CH2NMe2 group.
Scheme 1 shows the synthetic paths of compounds 5-10.
The -CH2NMe2 group of 2 exhibits the ortho-directing
functionality similar to that observed in N,N-dimethylamino-
methylferrocene (1), as described above. Actually, the lithiation
1
analysis, H NMR, and MS. Furthermore, the X-ray crystal
structure of the product 5 was determined.
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Biochem. 2003, 96, 394.
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Transition-metal coordination complexes have been widely
studied for the development of effective bioactive agents such
as antimicrobial, antibacterial, and antitumor agents.28-37 In the
research field the investigation of antimicrobial and cytotoxic
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Merrill, R. E.; Smart, J. C. J. Organomet. Chem. 1971, 27, 241.
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M. A.; Alam, M. S. Online J. Biol. Sci. 2002, 2, 797.
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Islam, A.; Farooque, M. A.; Alam, A. Pak. J. Biol. Sci. 2004, 7, 1113.
(38) Haque, E.; Hossen F.; Islam, S.; Noman, A. S. M. Int. J. Agri. Biol.
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Org. Chem. 1959, 24, 824.
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1965, 87, 1241.

Homoannularly Disubstituted Ferrocene DeriVatiVes
Organometallics, Vol. 26, No. 25, 2007 6221
Scheme 1. Synthetic Paths of Ferrocene Derivatives 5-10
of 2 introduced lithium into the Cp ring at the ortho-position
of -CH2NMe2 groups to provide 1-dimethylaminomethyl-5-
lithioferrocene derivative 3. The substitutions of 3 with equimo-
lar amounts of trimethylchlorosilane (Me3SiCl) and tribenzyl-
stannyl chloride ((PhCH2)3SnCl) provided the ferrocene
derivatives 5 and 6 homoannularly disubstituted by As and Si
and by As and Sn in yields of 33% and 47%, respectively. The
yield of 5 is comparable to the substitution yield (37%) of
1-(N,N-dimethylaminomethyl)-2-lithioferrocene with Me3SiCl.43
In contrast, the substitution of 3 with diphenylarsino chloride
(Ph2AsCl) gave a lower yield of 20%.44
The substitution of compound 3 with half-equimolar amounts
of dimethyldichlorosilane (Me2SiCl2) and dibutylstannyl dichlo-
ride (Bu2SnCl2) provided the dimethylsilicon- and the dibutyltin-
bridged bis(diphenylarsinoferrocene) derivatives 7 and 8 in
yields of 18% and 34%, respectively. The dissociation energy
of Sn-Cl bonds is smaller than that of Si-Cl bonds.45,46
Therefore, the higher yields of 8 might result from the more
reactive Sn-Cl bond as compared to the Si-Cl bond. Further-
more, the atomic radius of tin is significantly larger than that
of silicon, so that the tetrahedral structure formed by tin has
more spatial advantage. This also would contribute to the higher
yield of 8 than that of 7. The yields of the half-equimolar
substitution are lower than those of the equimolar substitution
mentioned above. The substitution of 1-(N,N-dimethylamino-
methyl)-2-lithioferrocene with half-equimolar amounts of Me2-
SiCl2 and Bu2SnCl2 gave yields of 22%43 and 43%,47 respec-
tively. The half-equimolar substitution yields from 1-(N,N-
dimethylaminomethyl)-2-lithioferrocene are higher than those
from compound 3, which contains the bulky diphenylarsino
group. Therefore, the lowering of the half-equimolar substitution
yields from 3 is attributed to the steric hindrance caused by the
spatial bulkiness of the substituted ferrocene molecules to be
bridged.
The lithiation of 2 by n-BuLi in the presence of TMEDA
introduces lithium into the 5, 1′-positions to provide the
dilithiated ferrocene derivative 4. The substitution of 4 with two
times the equimolar amount of Me3SiCl gave the trisubstituted
derivative 9 containing a diphenylarsino (-AsPh2) group and
5,1′-bis(trimethylsilyl () -SiMe3)) groups in 33% yield. The
yield was much lower than the substitution yield (57%25) of
1-(N,N-dimethylaminomethyl)-5,1′-dilithioferrocene with Me3-
SiCl. Similarly, compound 10 was synthesized by the n-BuLi-
TMEDA procedure.27 First, N,N-dimethylaminomethylferrocene
(1) was lithiated and then substituted with Me3SiCl. After the
n-BuLi-TMEDA dilithiation of the resulting trimethylsilylfer-
rocene derivative, the substitution with two times the equimolar
amount of Ph2AsCl gave the trisubstituted derivative 10
containing a -SiMe3 group and 5,1′-bis(-AsPh2) groups in an
overall yield of 18% from 1.
In summary, the ferrocene derivatives (5-10) homoannularly
disubstituted and heteroannularly trisubstituted by As and Si
or Sn were synthesized from N,N-dimethylaminomethylfer-
rocene (1) and its diphenylarsino derivative 2 through mono-
(43) Du, H. H.; Shi, X. X.; Ye, J. D.; Shi, S. J. Chem. J. Chin. UniV.
1997, 18, 1642.
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W. Chem. J. Chin. UniV. 2001, 22, 1496.
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822.
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23, 62.
(46) Jackson, R. A. J. Organomet. Chem. 1979, 166, 17.

6222 Organometallics, Vol. 26, No. 25, 2007
Du et al.
Figure 2. Definitions of the torsion (R) and tilt (â) angles of Cp
rings.
Table 2. Selected Bond Lengths and Angles for Compound
5
Bond Lengths (Å)
Fe-C(1)
Fe-C(2)
Fe-C(3)
Fe-C(4)
Fe-C(5)
Fe-C(6)
Fe-C(7)
Fe-C(8)
Fe-C(9)
Fe-C(10)
As-C(2)
As-C(14)
As-C(20)
Si-C(5)
2.039(4)
2.043(4)
2.039(4)
2.034(4)
2.054(4)
2.032(5)
2.036(5)
2.043(5)
2.026(5)
2.045(5)
1.953(4)
1.960(4)
1.966(5)
1.866(4)
1.849(5)
1.870(7)
1.870(6)
Figure 1. ORTEP view of compound 5 with 30% probability
thermal ellipsoids.
Table 1. Crystal Data and Structure Refinement for
Compound 5
empirical formula
fw (g/mol)
C28H34AsFeNSi
543.42
temp (K)
293
cryst size (mm)
cryst syst
0.8 × 0.8 × 0.6
Si-C(11)
Si-C(12)
Si-C(13)
triclinic
space group
unit cell dimens
P1
a ) 1.0079(2) nm
b ) 1.2213(2) nm
c ) 1.2333(2) nm
R ) 73.54(3)°
â ) 70.10(3)°
γ ) 75.02(3)°
1.3467(4)
Bond Angles (deg)
C(26)-C(1)-C(2)
C(26)-C(1)-C(5)
C(1)-C(5)-Si
C(1)-C(2)-As
C(2)-C(1)-C(5)
Cp-torsion (R)
Cp-tilt (â)
126.2(4)
125.7(4)
130.6(3)
123.5(3)
108.0(4)
12
volume (nm3)
Z (molecules/cell)
D
2
calc (g/cm3)
1.340
0.18
radiation (λ, Å)
absorp coeff (mm-1
F(000)
0.71073 (Mo KR)
)
1.839
Cp protons are adjacent to each other and that the -AsPh2 group
and the -SiMe3 group are located in the ortho-positions of the
-CH2NMe2 group. The singlet peak of three methyl groups
observed at a quite high magnetic field of 0.24 ppm implies
that the three methyl groups are magnetically equivalent and
exist on the Si atom. The 1H NMR of 6 also showed an apparent
triplet peak corresponding to the seven protons of trisubstituted
564
θ range for data collection (deg)
2.18-26.00
-12 e h e 12
-12 e k e 0
-15 e l e 14
5304
5043 [R(int) ) 0.0215]
5038/0/289
1.017
R1 ) 0.0462
wR2 ) 0.1143
R1 ) 0.0959
wR2 ) 0.1389
0.497, -0.812
index ranges
no. of reflns collected
no. of indep reflns
no. of data/restraints/params
goodness of fit on F2
final R indices [I > 2σ(I)]
1
and nonsubstituted Cp rings. In the H NMR spectrum of 7, a
multiplet peak of 14 protons was observed at 4.22-4.55 ppm,
in which the outstanding singlet peak corresponding to the
nonsubstituted Cp rings was observed at 4.22 ppm. The two
methyl groups existing on the Si atom were observed indepen-
dently at 0.93 and 1.09 ppm. This indicates that the two methyl
groups are located under chemically inequivalent conditions
caused by the anisotropy of the molecular structure of 7. In the
case of 8, the two butyl groups existing on the Sn atom are
chemically inequivalent and were observed at 0.70-1.66 ppm
as a multiplet peak. In the MS spectrum of 9, the M+ peak was
R indices (all data)
largest diff peak and hole (e Å-3
)
and dilithiation and subsequent substitution with the organo-
substituted chlorides of main-group elements. The results of this
work have indicated that the substitution efficiency is largely
influenced by the spatial volumes of the main-group elements
and the lithiated ferrocene molecules.
1
confirmed at m/z ) 615. The H NMR spectrum gave two
Structural Characterization of 5-10. All ferrocene deriva-
tives 5-10 were identified by elemental analysis, 1H NMR, and
MS. The MS spectrum of 5 gave the molecular ion (M+) peak
at m/z ) 543, which substantiates the validity of the molecular
formula of 5. The 1H NMR spectrum of 5 showed a triplet peak
of seven protons at 3.83-4.02 ppm, which was not the intrinsic
triplet peak split at the intensity ratio of 1:2:1 by spin-spin
coupling but the peaks comprised of two weak peaks with almost
the same intensity and a singlet peak with high intensity. The
apparent triplet peak indicates the presence of trisubstituted and
nonsubstituted Cp rings. The tips of the two weak peaks were
slightly split, with a coupling constant 3J ) 2.6 Hz. The
observation of the spin-spin coupling indicates that the two
singlet peaks showing the -SiMe3 protons at 0.13 and 0.43 ppm,
which indicates that the two -SiMe3 groups are located under
chemically inequivalent conditions. Similarly, the 1H NMR
spectrum of 10 gave two singlet peaks showing the phenyl
protons of the chemically inequivalent -AsPh2 groups at 7.20
and 7.26 ppm. The MS analysis of 10 was performed by fast
atom bombardment mass spectrometry (FAB-MS). The FAB-
MS spectrum did not give the M+ peak but the m/z ) 727 peak
of the fragment ion losing the dimethylamino (-NMe2) group
from the molecule.
X-ray Structural Analysis of 5. The crystal data and the
structure refinement for 5 are summarized in Table 1. Compound

Homoannularly Disubstituted Ferrocene DeriVatiVes
Organometallics, Vol. 26, No. 25, 2007 6223
Table 3. Percentage of the Growth Inhibition of Crop-Blight-Inducing Fungi by Ferrocene Derivatives
head blight
(wheat)
early blight
(tomato)
wilt disease
(cotton)
ring rot
disease (apple)
brown blotch
disease (peanut)
product
Ra
Ib
R
I
R
I
R
I
R
I
5
6
21.5
21.8
19.5
0
23.8
22.7
30.9
17.1
16.5
10.7
15.6
10.6
16.7
45.9
21.2
36.8
20.1
18.9
0
0
45.4
48.6
19.5
17.2
16.9
0
27.0
35.6
36.7
14.7
14.8
14.6
0
0
0
0
10
Ac
100
100
100
100
a R: average diameter (mm) of inhibition zone. b I: percentage (%) of inhibition. c A: 50% carbendazim wettable powder as a control.
5 crystallizes from anhydrous ethanol as an brownish-yellow
crystal in the triclinic space group P1. Figure 1 shows the
ORTEP diagram of the molecular structure of 5. Selected bond
lengths and angles are listed in Table 2. The distortion of the
Cp ring arrangements is defined by Cp torsion (R) and Cp tilt
(â) angles in Figure 2. The Cp rings are arranged in a nearly
eclipsed conformation with an average torsion angle of R )
12° and have an almost parallel orientation with a tilt angle of
â ) 0.18°. The average bond length of Fe-C (Cp1-5) is 2.042
Å, which is comparable to that (2.037 Å) of Fe-C (Cp6-10).
Although the Fe-C(5) bond length (2.054 Å) of the carbon
atom bearing the -SiMe3 group is slightly longer than the
average bond length, the Fe-C(Cp) bond lengths are proved
to be not largely influenced by the incorporated -CH2NMe2,
-AsPh2, and -SiMe3 groups. The C(26)-C(C1)-C(C2) and
C(26)-C(C1)-C(C5) angles are almost equivalent (126°),
which indicates that the C(26)-C(Cp) bond is undistortedly
attached on the elongation of the axis connecting C(C1) and
the Cp ring center. The C(1)-C(2)-As angle (124°) is
slightly bent toward the C(26)-C(Cp) bond, different from
the equivalent C(26)-C(Cp)-C(Cp) angles by 2°. In contrast,
the C(1)-C(5)-Si angle (131°) is bent in the opposite
direction of the C(26)-C(Cp) bond by 5°. The irregularity of
the bending directions implies that the distortions in the bond
angles of C(1)-C(2)-As and C(1)-C(5)-Si result not
from intramolecular steric effects but from the crystal-packing
effects.
Examination of the Fungicidal Activity of 5, 6, and 10
against Fungi that Cause Crop Plant Disease. Table 3 shows
the percent inhibition of fungi growth by the ferrocene deriva-
tives 5, 6, and 10 and, for comparison, by a commercial
pesticide, carbendazim wettable powder. Compound 5 exhibited
low but unambiguous fungicidal activities against fungi bringing
on head blight of wheat, early blight of tomato, and ring-rot
disease of apple. In contrast, no fungicidal activity was observed
for fungi causing wilt disease of cotton and brown blotch disease
of peanut. Compound 6 largely improved the percent inhibition
of fungi for early blight of tomato, wilt disease of cotton, and
ring-rot disease of apple, although no improvement was
observed for head blight of wheat and brown blotch of peanut.
The ferrocene derivatives 5 and 6 homoannularly disubstituted
by organoarsenic and organosilicon or organotin were proved
to exhibit fungicidal activity except for wilt disease of cotton
and/or brown blotch disease of peanut. However, the absolute
fungicidal effects observed for 5 and 6 are lower than those of
the carbendazim wettable powder. The ferrocene derivative 10
heteroannularly trisubstituted by organosilicon and organoarsenic
further improved the percent inhibition for head blight of wheat
and early blight of tomato. Particularly, the percent inhibition
(45.9%) for early blight of tomato reaches approximately 3 to
4 times the value observed for 5 and 6. Furthermore, the
fungicidal activity of 10 for early blight of tomato is more than
twice that of the carbendazim wettable powder. The results of
the percent inhibition test for crop-blight-inducing fungi indicate
that the fungicidal activity of the ferrocene derivatives has a
close relation to the kind and number of substituted main-group
elements and the introduction position of the main-group
elements on the Cp rings of ferrocenes.
Conclusions
We have successfully synthesized the ferrocene derivatives
disubstituted (5 and 6) and trisubstituted (9 and 10) by As and
Si or Sn, as well as the dimethylsilicon- and dibutyltin-bridged
bis(diphenylarsinoferrocene) derivatives (7 and 8). The -CH2-
NMe2 group of the diphenylarsinoferrocene derivative 2 (a
starting compound of 5-9) facilitates the lithiation of the Cp
ring and introduces lithium into the ortho-position of the -CH2-
NMe2 group by the directing functionality. The monolithiation
of 2 provides the 5-lithioferrocene derivative 3 by the ortho-
directing -CH2NMe2 functionality. The dilithiation of 2 by the
n-BuLi-TMEDA procedure provides the 5,1′-dilithioferrocene
derivative 4. The equimolar substitutions of 3 with Me3SiCl
and (PhCH2)3SnCl provide the diphenylarsinoferrocene deriva-
tives 5 and 6, containing Si and Sn, respectively. The substitu-
tions of 3 with half-equimolar amounts of Me2SiCl2 and
Bu2SnCl2 provide the Me2Si- and the Bu2Sn-bridged bis-
(diphenylarsinoferrocene) derivatives 7 and 8. The equimolar
and half-equimolar substitutions gave higher yields for Sn than
for Si. In addition, the half-equimolar substitutions gave lower
yields than those of the equimolar substitutions. It is therefore
concluded that the substitution yields are influenced by the
spatial factor of the main-group elements (i.e., atomic radius)
and the ferrocene molecules (i.e., spatial bulkiness) to be reacted.
The substitution of 4 with twice equimolar amounts of Me3-
SiCl gave the trisubstituted derivative 9, containing a -AsPh2
group and 5,1′-bis (-SiMe3) groups. Compound 10 was
synthesized from 1 through monolithiation and followed by
substitution with Me3SiCl and then dilithiation and substitution
with Ph2AsCl. The substitution of the dilithiated trimethyl-
silylferrocene derivative with twice equimolar amounts of Ph2-
AsCl gave the trisubstituted derivative 10, containing a -SiMe3
group and 5,1′-bis (-AsPh2) groups. In the application of 5, 6,
and 10 as fungicides, the derivative 10 exhibited much higher
percent inhibition of fungal growth for early blight of tomato,
compared with 5 and 6. The results of the percent inhibition
test have indicated that the fungicidal activity of the ferrocene
derivatives has a close relation to the kind and number of main-
group elements and their introduction position on the Cp rings
of ferrocenes.
Experimental Section
General Remarks. All reagents were purchased from Beijing
Chemical Reagent Co. and used as received. Solvents were dried
and distilled prior to use by standard procedures. 2-(Dipheny-
larsino)-1-(N,N-dimethylaminomethyl)ferrocene (2),48 tribenzyltin
(48) Du, H. H.; Shi, S. J. Chem. J. Chin. UniV. 1993, 14, 1087.

6224 Organometallics, Vol. 26, No. 25, 2007
Du et al.
chloride,49 dibutyltin dichloride,50 N,N-dimethylaminomethylfer-
rocene (1),51 and diphenylchloroarsine52 were prepared according
to the literature. All experiments were performed under an inert
atmosphere (prepurified N2) using either standard Schlenk-line
techniques53 or an inert-atmosphere glovebox. Melting points were
determined on a microscopic apparatus without correction. Elemen-
tal analyses were performed with a Carlo Erba 1106 elemental
analyzer. 1H NMR spectra were recorded on a Bruker AC 80
spectrometer, using deuterated chloroform (CDCl3) as solvent and
tetramethylsilane (TMS) as an internal standard. Mass spectra were
recorded on a VG70 SE GC/MS gas chromatography mass
spectrometer. Crystallographic data were obtained on a Rigaku
AFC6S diffractometer (graphite monochromator, Mo KR radiation,
λ ) 0.71073 Å). All calculations were performed using the
SHELXL-93 program. The structure was solved by direct methods
and was refined using full-matrix least-squares with anisotropic
thermal parameters for all non-hydrogen atoms, and all hydrogen
atoms were included but not refined. Percent inhibition tests of
fungal growth by ferrocene derivatives were conducted using a
plating method, which was repeated nine times for each sample.
The concentration of ferrocene derivatives was 50 ppm in all runs,
and 50% carbendazim wettable powder was used as a control.
General Procedure for the Synthesis of Products 5-9.
Compound 2 and anhydrous diethyl ether (Et2O) were placed into
a three-neck round-bottom flask equipped with a dropping funnel,
a reflux condenser, and a gas inlet. n-BuLi in petroleum ether was
transferred to the flask, and the mixture was magnetically stirred
at room temperature for 1 h, followed by reflux for 15 min. The
anhydrous ether solution of organo-substituted chlorides of main-
group elements was added dropwise into the above lithiated solution
and then stirred at 34-35 °C for 20 h. After cooling, water was
added and the mixture was separated. The obtained aqueous phase
was extracted with Et2O three times. The organic phase was
gathered and dried by anhydrous magnesium sulfate (MgSO4). After
filtrating and evaporating the solvent, the crude product was purified
by alkaline alumina (Al2O3) column chromatography and/or re-
crystallization to give 5-9. The products were characterized as
follows.
81.0 °C. Anal. Calcd for C46H46NAsFeSn: C, 64.07; H, 5.38; N,
1.62. Found: C, 64.06; H, 5.53; N, 1.44. 1H NMR (δ, ppm): 7.34-
6.65 (m, 25H, Ph), 4.08-3.54 (m, 7H, Cp), 3.15-2.78 (t, 2H,
CH2N), 2.38 (s, 6H, NMe2), 1.88 (s, 6H, CH2Ph).
Bis[2-(N,N-dimethylaminomethyl)-3-(diphenylarsino)ferroce-
nyl]dimethylsilicane (7). The product was purified by alkaline
Al2O3 column chromatography with petroleum ether/EtOAc (v/v
3:1) as an eluent to give 7 as a yellow solid. Yield: 18%. Mp:
208-214 °C. Anal. Calcd for C52H56N2As2Fe2Si: C, 62.54; H, 5.65;
1
N, 2.81. Found: C, 62.32; H, 5.70; N, 2.45. H NMR (δ, ppm):
7.98-7.42 (m, 20H, Ph), 4.55-4.22 (m, 14H, Cp), 3.87 (s, 4H,
CH2), 2.21(s, 12H, NMe2), 1.09, 0.93 (2s, 6H, SiMe2).
Bis[2-(N,N-dimethylaminomethyl)-3-(diphenylarsino)ferrocenyl]-
dibutyltin (8). The product was purified by alkaline Al2O3 column
chromatography with petroleum ether/EtOAc (v/v 4:1) as an eluent
to give 8 as a yellow solid. Yield: 34%. Mp: 208-214 °C (dec).
Anal. Calcd for C58H68N2As2Fe2Sn: C, 59.37; H, 5.84; N, 2.39.
Found: C, 59.09; H, 5.90; N, 2.12. 1H NMR (δ, ppm): 7.60-6.93
(m, 20H, Ph), 4.30-3.76 (m, 14H, Cp), 3.33 (s, 4H, CH2), 1.81 (s,
12H, CH3), 1.66-0.70 (m, 18H, Bu).
2-(Diphenylarsino)-5,1′-bis(trimethylsilyl)-1-(N,N-dimethy-
laminomethyl)ferrocene (9). The product was recrystallized from
petroleum ether (60-90 °C) to give 9 as a brownish-yellow
crystalline solid. Yield: 33%. Mp: 105.5-106.5 °C. Anal. Calcd
for C31H42NFeSi2As: C, 60.48; H, 6.88; N, 2.28. Found: C, 60.63;
1
H, 6.79; N, 2.15. H NMR (δ, ppm): 7.85-7.37 (m, 10H, Ph);
4.55-3.38 (m, 6H, Cp); 3.53 (s, 2H, CH2); 2.00 (s, 6H, NMe2);
0.43,0.13 (2s, 18H, SiMe3). MS (FAB): m/z 615 (M+).
Synthesis of 2-(Trimethylsilyl)-5,1′-bis(diphenylarsino)-1-
(N,N-dimethylaminomethyl)ferrocene (10). Compound 1 (0.85
mL, 5.0 mmol) and anhydrous Et2O (10 mL) were placed into a
100 mL three-neck round-bottom flask. n-BuLi in petroleum ether
(4.0 mL, 1.3 mol/L, 5.2 mmol) was slowly added to the flask, and
the mixture was stirred at room temperature for 1 h, followed by
reflux for 15 min. Me3SiCl (0.65 mL, 5.2 mmol) dissolved in
anhydrous Et2O (10 mL) was added dropwise into the above
lithiated solution, and the mixture was stirred at 34-35 °C for 18
h. Then, a n-BuLi solution (8.0 mL, 1.3 mol/L, 10.4 mmol) and
TMEDA (0.80 mL, 5 mmol) were added, and the mixture was
stirred for 5 h. Ph2AsCl (1.90 mL, 10.2 mmol) dissolved in
anhydrous Et2O (10 mL) was added dropwise into the above
reactant solution at 34-35 °C for 24 h. After cooling, water (20
mL) was added and the mixture was separated. The aqueous phase
was extracted in anhydrous Et2O (10 mL) three times. The eluted
organic phase was gathered and dried by anhydrous MgSO4. After
evaporating the solvent, the crude product was recrystallized from
petroleum ether (60-90 °C) to give 10 as a yellow crystalline solid.
Yield: 18.0%. Mp: 167-168 °C. Anal. Calcd for C40H43NAs2-
SiFe: C, 62.27; H, 5.62; N, 1.82. Found: C, 62.28; H, 5.71; N,
1.78. 1H NMR (δ, ppm): 7.26-7.20 (2s, 20H, Ph), 4.43-3.35 (m,
6H, Cp), 3.43 (s, 2H, CH2), 1.88 (s, 6H, NMe2), 0.38 (s, 9H, SiMe3).
MS (FAB): m/z 727 (M+ - NMe2).
5-(Trimethylsilyl)-2-(diphenylarsino)-1-(N,N-dimethylami-
nomethyl)ferrocene (5). The product was purified by alkaline
Al2O3 column chromatography with petroleum ether/ethyl acetate
(EtOAc) (v/v 20:1) as an eluent and recrystallization from anhydrous
ethanol (EtOH) to give 5 as a brownish-yellow crystalline solid.
Yield: 33%. Mp: 102.5-104.5 °C. Anal. Calcd for C28H34-
NAsSiFe: C, 61.88; H, 6.31; N, 2.58. Found: C, 61.71; H, 6.26;
1
N, 2.39. H NMR (δ, ppm): 7.58-7.10 (m, 10H, Ph), 4.02-3.83
(s and d, 7H, Cp), 3.30 (s, 2H, CH2), 1.75 (s, 6H, NMe2), 0.24 (s,
9H, SiMe3). MS (EI): m/z (% relative intensity) 543 (M+, 100),
499 (11), 423 (33), 349 (37), 299 (12), 227 (5), 121 (5), 73 (26).
5-(Tribenzyltin)-2-(diphenylarsino)-1-(N,N-dimethylaminom-
ethyl)ferrocene (6). The product was purified by alkaline Al2O3
column chromatography with petroleum ether/EtOAc (v/v 4:1)
as an eluent and recrystallization from anhydrous EtOH to give 6
as a brownish-yellow crystalline solid. Yield: 47%. Mp: 79.5-
Acknowledgment. We are grateful to the National Natural
Science Foundation of China (Grant No. 29372037) for financial
support of this work.
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Supporting Information Available: Text giving details of the
characterization of 5 and tables and a CIF file giving full
crystallographic descriptions of 5. This material is available free
of charge via the Internet at http://pubs.acs.org.
OM7004468