4-Silapiperidine and 4-silapiperidinium derivatives: Syntheses and structural characterization

Article abstract of DOI:10.1016/j.jorganchem.2004.08.023

A series of novel 4-silapiperidine and 4-silapiperidinium derivatives, with two silicon-bound aryl groups and various N-organyl groups, have been synthesized and structurally characterized (solution ¹H, ¹³C, ¹⁹F, and

Full text of DOI:10.1016/j.jorganchem.2004.08.023

Journal of Organometallic Chemistry 690 (2005) 33–47
www.elsevier.com/locate/jorganchem
4-Silapiperidine and 4-silapiperidinium derivatives: syntheses
and structural characterization
*
Tilman Heinrich, Christian Burschka, Martin Penka, Brigitte Wagner, Reinhold Tacke
Institut fu¨r Anorganische Chemie, Universita¨t Wu¨rzburg, Am Hubland, D-97074 Wu¨rzburg, Germany
Received 11 May 2004; accepted 8 August 2004
Available online 28 September 2004
Abstract
A series of novel 4-silapiperidine and 4-silapiperidinium derivatives, with two silicon-bound aryl groups and various N-organyl
groups, have been synthesized and structurally characterized (solution 1H, 13C, 19F, and 29Si NMR spectroscopy; eight crystal struc-
ture analyses). These synthetic and structural investigations provide the basis for the development of novel silicon-based drugs
containing a 4-silapiperidine or 4-silapiperidinium skeleton.
ꢀ 2004 Elsevier B.V. All rights reserved.
Keywords: 4-Silapiperidine; 4-Silapiperidinium; Silicon; Silicon-based drugs
R1
R1 = R2 = aryl, alkyl
R3 = alkyl, H
1. Introduction
Si
N
R3
R2
Since the first 4-silapiperidines of the formula type A
have been described in the literature in the 1980s [1–3],
there have been only a few reports about further deriv-
atives of this class of compound [4–6]. The majority of
these compounds contain two phenyl (R1 = R2 = Ph)
or two methyl groups (R1 = R2 = Me) attached to the
silicon atom and various alkyl groups (R3) bound to
the nitrogen atom. Compounds of type A with R3 = H
have also been mentioned in the literature [2,4], but
there are no easily accessible publications describing
their preparation. 4-Silapiperidines have been studied
for their pharmacological activity [1,2,6] and have re-
cently also gained interest in protecting group chemistry
[5].
A
Cl
O
El
N
CH2 CH2 CH2
C
F
HO
El = C: Haloperidol (1a)
El = Si: Sila-haloperidol (1b)
In context with our research program dealing with
the development of silicon-based drugs [7,8], we have re-
cently synthesized sila-haloperidol (1b), a silicon ana-
logue of the neuroleptic haloperidol (1a). While the
synthesis of sila-haloperidol (1b) itself has already been
published [6], we here report on the synthesis and struc-
tural characterization of a series of further 4-silapiperi-
dine and 4-silapiperidinium derivatives (compounds 5,
6 Æ HCl, 8, 9, 13 Æ HCl, 15 Æ HCl Æ 0.5EtOH, 17 Æ H2O,
and 18 Æ HCl) that have been prepared in synthetic stud-
ies at the beginning of the sila-haloperidol project.
*
Corresponding author. Tel.: +49 931 888 5250; fax: +49 931 888
4609.
E-mail address: r.tacke@mail.uni-wuerzburg.de (R. Tacke).
0022-328X/$ - see front matter ꢀ 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2004.08.023

34
T. Heinrich et al. / Journal of Organometallic Chemistry 690 (2005) 33–47
of Ph2SiCl2 with vinylmagnesium chloride yielded
R
diphenyldivinylsilane (2) [9], which upon reaction with
hydrogen bromide, catalyzed by dibenzoyl peroxide,
gave bis(2-bromoethyl)diphenylsilane (3) [1]. Treatment
of 3 with benzylamine, in the presence of triethylamine,
followed by reaction with hydrogen chloride,
afforded 1-benzyl-4,4-diphenyl-4-silapiperidinium chlo-
ride (4 Æ HCl). Treatment of 4 Æ HCl with sodium
hydroxide gave the amine 4, which upon reaction with
2,2,2-trichloroethyl chloroformate [10] yielded 5. This
compound was then reacted successively with zinc/acetic
acid and hydrogen chloride to give 6 Æ HCl [11].
1-{3-[2-(4-Fluorophenyl)-1,3-dioxolan-2-yl]propyl}-
1-methyl-4,4-diphenyl-4-silapiperidinium iodide (8) and
1-[4-oxo-4-(4-fluorophenyl)butyl]-4,4-diphenyl-4-silapi-
peridine (9) were synthesized according to Scheme 2,
starting from 3 or 6 Æ HCl. Thus, treatment of 3 with 3-
[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propylamine [12],
in the presence of triethylamine, yielded 1-{3-[2-(4-fluor-
ophenyl)-1,3-dioxolan-2-yl]propyl}-4,4-diphenyl-4-sila-
piperidine (7) (Method A). Alternatively, 7 was prepared
by treatment of 6 (obtained from 6 Æ HCl by reaction with
sodium hydroxide) with 2-(3-chloropropyl)-2-(4-fluoro-
phenyl)-1,3-dioxolane [13] in the presence of potassium
iodide and potassium carbonate (Method B). Finally,
reaction of 7 with methyl iodide afforded 8, and hydroly-
sis of 7 with hydrochloric acid gave 9.
1-Benzyl-4,4-bis(4-chlorophenyl)-4-silapiperidinium
chloride (13 Æ HCl) and 4,4-bis(4-chlorophenyl)-1-sila-
piperidinium chloride (15 Æ HCl; isolated as the hemi-
ethanol solvate 15 Æ HCl Æ 0.5EtOH) were synthesized
according to Scheme 3, starting from tetramethoxysi-
lane. Thus, treatment of Si(OMe)4 with (4-chlorophe-
nyl)magnesium bromide gave bis(4-chlorophenyl)-
dimethoxysilane (10), which upon reaction with
vinylmagnesium chloride afforded bis(4-chlorophe-
nyl)divi- nylsilane (11). Treatment of 11 with hydrogen
bromide, in the presence of dibenzoyl peroxide, yielded
bis(2-bromoethyl)bis(4-chlorophenyl)silane (12) [6]. Cyc-
lization of 12 with benzylamine, in the presence of trieth-
ylamine, followed by reaction with hydrogen choride,
gave 13 Æ HCl. Treatment of 13 Æ HCl with sodium
hydroxide (formation of 13) and subsequent reaction
O
C
Si
NH
Si
N
OCH2CCl3
R
5
6: R = H
15: R = Cl
R
R
Me
N
O
O
Si
CH2 CH2 CH2
C
F
I
8: R = H
17: R = Cl
O
Si
N
CH2 CH2 CH2
C
F
9
Cl
Si
N
CH2
Cl
13
Cl
Cl
S
S
Si
N
CH2 CH2 CH2
C
F
18
2. Results and discussion
2.1. Syntheses
2,2,2-Trichloroethyl 4,4-diphenyl-4-silapiperidine-1-
carboxylate (5) and 4,4-diphenyl-4-silapiperidinium
chloride (6 Æ HCl) were synthesized according to Scheme
1, starting from dichlorodiphenylsilane. Thus, treatment
Cl
Cl
CH CH2
CH2 CH2 Br
Si
CH2=CHMgCl
HBr [DBP]
Si
Si
1) H2N CH2
2) HCl
, NEt3
CH CH2
CH2 CH2 Br
2
3
1) NaOH
2) ClC(O)OCH2CCl3
1) Zn/HOAc
2) HCl
H
O
Si
NH2
Si
N
C
OCH2CCl3
Si
N
Cl
CH2
Cl
6 • HCl
5
4 • HCl
Scheme 1.

T. Heinrich et al. / Journal of Organometallic Chemistry 690 (2005) 33–47
35
CH2 CH2 Br
NaOH
Si
NH
Si
NH2 Cl
Si
CH2 CH2 Br
3
6
6 • HCl
O
O
, NEt
F
NH2 CH2 CH2 CH2
C
Method A
O
O
3
Cl CH2 CH2 CH2
C
F, KI, K2CO3
O
O
Method B
Si
N
CH2 CH2 CH2
C
F
7
H2O [H3O+]
MeI
Me
O
O
O
Si
N
CH2 CH2 CH2
C
F
Si
N
CH2 CH2 CH2
C
F
I
8
9
Scheme 2.
Cl
Cl
Cl
Cl
CH CH2
CH CH2
OMe
OMe
CH2 CH2 Br
ClC6H4MgBr
CH2=CHMgCl
HBr [DBP]
Si(OMe)4
Si
Si
Si
CH2 CH2 Br
Cl
Cl
10
11
12
1) H2N CH2
2) HCl
, NEt3
Cl
Cl
Cl
Cl
Cl
Cl
1) NaOH
2) ClC(O)OCHClCH3
1) MeOH
2) EtOH
H
O
Si
N
Cl
Si
N
C
OCHClCH3
CH2
Si
NH2
Cl
15 • HCl • 0.5 EtOH
14
13 • HCl
Scheme 3.
with 1-chloroethyl chloroformate [14] yielded 1-chloro-
ethyl 4,4-bis(4-chlorophenyl)-4-silapiperidine-1-carb-
oxylate (14; isolated as crude product, not purified and
characterized), which upon reaction with methanol
and recrystallization of the resulting product 15 Æ HCl
from ethanol afforded 15 Æ HCl Æ 0.5EtOH.
4,4-Bis(4-chlorophenyl)-1-{3-[2-(4-fluorophenyl)-
1,3-dioxolan-2-yl]propyl}-1-methyl-4-silapiperidinium
iodide (17) was synthesized according to Scheme 4,
starting from 12. Thus, cyclization of 12 with 3-[2-(4-
fluorophenyl)-1,3-dioxolan-2-yl]propylamine [12], in
the presence of triethylamine, gave 4,4-bis(4-chlorophe-
nyl)-1-{3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl}-
4-silapiperidine (16; isolated as crude product, not
purified and characterized), which upon treatment with
methyl iodide afforded 17. Crystallization of 17 from
ethanol/ethyl acetate/water gave the hydrate 17 Æ H2O.
4,4-Bis(4-chlorophenyl)-1-{3-[2-(4-fluorophenyl)-1,3-
dithian-2-yl]propyl}-4-silapiperidinium chloride (18 Æ
HCl) was synthesized according to Scheme 5, starting
from 12. Thus, cyclization of 12 with 3-[2-(4-fluorophe-
nyl)-1,3-dithian-2-yl]propylamine (19), in the presence
of triethylamine, gave 18, which upon treatment with
hydrogen chloride afforded the hydrochloride 18 Æ HCl.
Compound 19 was synthesized in three steps, starting
from commercially available 4-chloro-1-(4-fluorophe-
nyl)butan-1-one (Scheme 5). Thus, treatment of the ke-
tone with propane-1,3-dithiol, in the presence of

36
T. Heinrich et al. / Journal of Organometallic Chemistry 690 (2005) 33–47
O
O
Cl
NH2 CH2 CH2 CH2
C
F, NEt3
CH2 CH2 Br
Si
CH2 CH2 Br
Cl
Cl
12
Cl
Cl
Me
O
O
O
O
MeI
Si
N
CH2 CH2 CH2
C
F
Si
N
CH2 CH2 CH2
C
F
I
Cl
17
16
Scheme 4.
Cl
Cl
1) 19, Et3N
2) HCl
H
S
S
CH2 CH2 Br
Si
Si
N
CH2 CH2 CH2
C
F
Cl
CH2 CH2 Br
Cl
Cl
12
18 • HCl
O
S
S
S
S
HS CH2 CH2 CH2 SH, HCl
Cl CH2 CH2 CH2
C
F
CH2 CH2 CH2
C
C
F
F
Cl
O
20
NH
O
O
S
S
N2H4 • H2O
HCl
DBU
19 • HCl
H2N CH2 CH2 CH2
C
F
N
CH2 CH2 CH2
O
19
21
Scheme 5.
hydrogen chloride, yielded 2-(3-chloropropyl)-2-(4-
fluorophenyl)-1,3-dithiane (20), which upon reaction
with phthalimide, in the presence of 1,8-diazabicy-
clo[5.4.0]undec-7-ene (DBU), afforded 2-{3-[2-(4-fluo-
ally characterized by single-crystal X-ray diffraction.
The crystal data and the experimental parameters used
for the crystal structure analyses are summarized in
Table 1; selected bond lengths and angles are given
in Table 2. The molecular structures of the respective
4-silapiperidines and 4-silapiperidinium cations are de-
picted in Figs. 1–8.
As can be seen from Figs. 1–8, the 4-silapiperidine
and 4-silapiperidinium skeletons of all compounds stud-
ied adopt a chair conformation, with very similar bond
lengths and angles. The N-organyl groups of the 4-sila-
piperidine 9 and the 4-silapiperidinium derivatives
13 Æ HCl and 18 Æ HCl occupy the equatorial position.
In the case of the 4-silapiperidinium derivatives 8 and
17 Æ H2O, the N-methyl groups are found in the equato-
rial positions, whereas the axial sites are occupied by the
larger N-organyl substituents. In the carbamate 5, the
nitrogen atom, the carbon atoms C14, C15, and C17,
and the oxygen atoms O1 and O2 are localized in a
plane (sum of angles at N, 359.9ꢁ; sum of angles at
C17, 360.0ꢁ; maximum dihedral angle, 7.2ꢁ (C14–N–
C17–O1)).
rophenyl)-1,3-dithian-2-yl]propyl}phthalimide
(21).
Treatment of 21 with hydrazine hydrate finally gave
19, which was converted to the hydrogen chloride
19 Æ HCl for analytical purposes.
Compounds 4 Æ HCl, 5, 6 Æ HCl, 8, 9, 13 Æ HCl, 15 Æ
HCl Æ 0.5EtOH, 17, 17 Æ H2O, 18 Æ HCl, 19 Æ HCl, 20,
and 21 were isolated as colorless solids, whereas 7 and
19 were obtained as highly viscous oils. The identities
of all compounds were established by elemental analyses
(C, H, N, S; except for 7 and 19) and solution NMR
studies (1H, 13C, 19F, 29Si). In addition, the crystal struc-
tures of 5, 6 Æ HCl, 8, 9, 13 Æ HCl, 15 Æ HCl, 17 Æ H2O, and
18 Æ HCl were determined.
2.2. Crystal structure analyses
Compounds 5, 6 Æ HCl, 8, 9, 13 Æ HCl, 15 Æ
HCl Æ 0.5EtOH, 17 Æ H2O, and 18 Æ HCl were structur-

Table 1
Crystal data and experimental parameters for the crystal structure analyses of 5, 6 Æ HCl, 8, 9, 13 Æ HCl, 15 Æ HCl Æ 0.5EtOH, 17 Æ H2O, and 18 Æ HCl
5
6 Æ HCl
8
9
13 Æ HCl
15 Æ HCl Æ 0.5EtOH
17 Æ H2O
18 Æ HCl
Empirical formula
Formula mass (g molꢀ1
Collection T (K)
C
19H20Cl3NO2Si
C16H20ClNSi
289.87
C29H35FINO2Si
603.57
C26H28FNOSi
417.58
C23H24Cl3NSi
448.87
C17H21Cl3NO0.5Si
381.79
C29H35Cl2FINO3Si
690.47
C29H33Cl3FNS2Si
613.12
)
428.80
173(2)
173(2)
173(2)
173(2)
173(2)
173(2)
173(2)
173(2)
˚
k (Mo Ka) (A)
Crystal system
0.71073
Monoclinic
P21c (14)
8.6449(17)
11.318(2)
20.892(4)
90
0.71073
Orthorhombic
Pna21 (33)
9.3157(10)
19.3055(17)
8.8265(9)
90
0.71073
0.71073
Monoclinic
P21c (14)
19.065(4)
10.898(2)
11.107(2)
90
0.71073
0.71073
0.71073
0.71073
Monoclinic
P2/n (13)
12.9487(18)
7.8525(8)
27.881(4)
90
Orthorhombic
P212121(19)
9.8970(7)
11.0211(12)
20.4106(16)
90
Triclinic
ꢀ
Triclinic
ꢀ
Orthorhombic
Pbca (61)
13.2957(14)
13.7808(11)
31.808(2)
90
Space group (no.)
˚
a (A)
P1 ð2Þ
P1 ð2Þ
10.002(2)
11.169(2)
18.382(4)
93.87(3)
99.96(3)
112.85(3)
1843.2(6)
4
8.4497(11)
10.9075(19)
16.276(2)
90.514(19)
91.697(15)
97.287(18)
1487.2(4)
2
˚
b (A)
˚
c (A)
a (ꢁ)
b (ꢁ)
c (ꢁ)
90.50(3)
90
90
95.032(17)
90
99.63(3)
90
90
90
90
90
90
3
˚
V (A )
2044.1(7)
4
1587.4(3)
4
2824.0(6)
4
2275.2(8)
4
2226.3(3)
4
5828.1(9)
8
Z
Dcalc (g cmꢀ3
)
1.393
1.213
1.420
1.219
1.339
1.376
1.542
1.398
l (mmꢀ1
F(000)
)
0.520
0.303
1.208
0.128
0.475
0.562
1.334
0.526
888
616
1232
888
936
796
700
2560
Crystal dimensions (mm)
0.8 · 0.7 · 0.6
4.72–56.10
ꢀ11 ꢁ h ꢁ 11,
ꢀ14 ꢁ k ꢁ 14,
ꢀ27 ꢁ l ꢁ 25
19801
0.5 · 0.5 · 0.4
4.86–53.96
ꢀ11 ꢁ h ꢁ 11,
ꢀ23 ꢁ k ꢁ 24,
ꢀ11 ꢁ l ꢁ 10
10167
0.3 · 0.2 · 0.1
3.60–49.92
ꢀ15 ꢁ h ꢁ 15,
ꢀ9 ꢁ k ꢁ 9,
ꢀ33 ꢁ l ꢁ 32
26127
0.5 · 0.3 · 0.1
4.32–49.42
ꢀ22 ꢁ h ꢁ 22,
ꢀ12 ꢁ k ꢁ 12,
ꢀ13 ꢁ l ꢁ 13
16497
0.5 · 0.5 · 0.3
4.20–51.92
ꢀ12 ꢁ h ꢁ 11,
ꢀ13 ꢁ k ꢁ 13,
ꢀ25 ꢁ l ꢁ 25
15552
0.5 · 0.5 · 0.3
4.52–49.42
ꢀ11 ꢁ h ꢁ 11,
ꢀ13 ꢁ k ꢁ 13,
ꢀ21 ꢁ l ꢁ 21
17523
0.5 · 0.3 · 0.2
4.50–53.54
ꢀ10 ꢁ h ꢁ 9,
ꢀ13 ꢁ k ꢁ 13,
ꢀ20 ꢁ l ꢁ 20
17144
0.5 · 0.2 · 0.1
4.44–52.78
ꢀ16 ꢁ h ꢁ 16,
ꢀ17 ꢁ k ꢁ 17,
ꢀ38 ꢁ l ꢁ 36
38827
2h range (ꢁ)
Index ranges
Number of collected
reflections
Number of independent
reflections
4864
3127
4902
3857
4255
5911
5820
5888
Rint
0.0547
0.0412
0.0361
0.0353
0.0306
0.0493
0.0298
0.0747
Absorption correction
Maximum/minimum
transmission
–
–
–
–
7 indexed faces
0.8389/0.5836
–
–
–
–
–
–
8 indexed faces
0.885/0.699
–
–
Number of reflections
used
4864
3127
4902
3857
4255
5911
5820
5888
Number of restraints
Number of parameters
Sa
–
1
–
–
–
–
–
–
315
178
319
271
256
421
350
337
1.042
1.032
1.031
1.033
1.030
1.015
1.070
1.020
Weight parameters a/bb
R1c[I > 2r(I)]
wR2 (all data)
0.0562/0.5082
0.0371
0.1022
–
0.0549/0.0371
0.0261
0.0708
ꢀ0.04(5)
0.0419/0.8136
0.0251
0.0680
–
0.0523/0.2944
0.0327
0.0899
–
0.0319/0.5669
0.0225
0.0596
ꢀ0.04(4)
0.0742/0.0000
0.0404
0.1131
–
0.0477/1.0666
0.0296
0.0830
–
0.0755/0.1364
0.0386
0.1081
–
d
Absolute structure
parameter
Maximum/minimum
+0.494/ꢀ0.529
+0.255/ꢀ0.226
+0.389/ꢀ0.609
+0.246/ꢀ0.209
+0.256/ꢀ0.190
+0.525/ꢀ0.446
+0.743/ꢀ0.732
+0.466/ꢀ0.612
residꢀu3al electron density
˚
(e A
)
P
2
S ¼ f ½wðF 2o ꢀ F 2c Þ ꢂ=ðn ꢀ pÞg0:5; n = number of reflections; p = number of parameters.
a
2
b
c
wꢀ1 ¼ r2ðF 2oÞ þ ðaPÞ þ bP; with P ¼ ½maxðF o2 ; 0Þ þ 2F 2cꢂ=3.
P
P
R1 = ||Fo| ꢀ |Fc||/ |Fo|.
P
P
2
2
0:5
d
wR2 ¼ f ½wðF 2o ꢀ F c2Þ ꢂ= ½wðF 2oÞ ꢂg
.

38
T. Heinrich et al. / Journal of Organometallic Chemistry 690 (2005) 33–47
Table 2
˚
Selected bond lengths (A) and angles (ꢁ) for compounds 5, 6 Æ HCl, 8, 9, 13 Æ HCl, 15 Æ HCl Æ 0.5EtOH, 17 Æ H2O, and 18 Æ HCl
5
6 Æ HCl
8
9
13 Æ HCl
15 Æ HCl Æ 0.5EtOH
17 Æ H2O
18 Æ HCl
Si–C1
Si–C7
1.8724(17)
1.8680(16)
1.8794(15)
1.8721(17)
1.464(2)
1.4678(19)
1.3389(19)
–
1.8708(14)
1.8566(14)
1.8797(16)
1.8685(15)
1.495(2)
1.495(2)
–
1.875(2)
1.875(2)
1.8811(19)
1.8759(19)
1.525(2)
1.522(2)
1.514(2)
1.506(2)
1.520(3)
1.522(3)
1.8752(16)
1.8726(16)
1.8607(15)
1.8667(15)
1.4704(18)
1.4679(19)
1.4749(18)
–
1.8753(14)
1.8639(14)
1.8774(14)
1.8734(14)
1.5072(17)
1.5100(19)
1.5114(18)
–
1.870(3)
1.859(3)
1.866(3)
1.865(3)
1.492(4)
1.490(4)
–
[1.868(3)]
1.881(3)
1.865(3)
1.877(2)
1.875(2)
1.520(3)
1.522(3)
1.520(3)
1.507(3)
1.526(3)
1.524(3)
1.872(2)
1.870(2)
1.871(2)
1.8697(19)
1.499(2)
1.507(2)
1.508(2)
–
[1.861(3)]
[1.861(3)]
[1.871(3)]
[1.493(4)]
[1.496(4)]
–
Si–C13
Si–C16
N–C14
N–C15
N–C17
N–C29
C13–C14
C15–C16
–
–
–
1.534(2)
1.533(2)
1.521(2)
1.520(2)
1.530(2)
1.534(2)
1.5212(19)
1.529(2)
1.518(4)
1.511(4)
[1.526(4)]
[1.515(4)]
1.521(3)
1.532(3)
C1–Si–C7
108.91(7)
109.96(7)
109.45(7)
111.99(7)
112.46(7)
103.98(7)
116.90(13)
119.37(13)
123.65(13)
110.27(10)
110.22(11)
111.71(13)
111.94(13)
–
112.28(6)
109.80(7)
108.97(7)
113.06(7)
110.81(6)
101.33(7)
116.54(12)
–
109.60(8)
112.03(9)
111.74 (9)
108.45(9)
111.76 (8)
103.10(8)
110.77(13)
109.77(14)
112.55(14)
115.58(13)
112.47(13)
114.56(15)
114.53(15)
105.81(14)
108.35(14)
109.33(13)
110.09(7)
109.07(7)
110.79(7)
112.06(7)
113.78(7)
100.67(7)
112.58(11)
109.50(11)
109.03(12)
110.52(10)
109.88(10)
112.98(12)
114.38(12)
–
111.46(6)
109.97(7)
111.62(7)
109.48(6)
111.32(7)
102.64(6)
112.77(11)
111.76(11)
109.02(11)
112.12(10)
113.32(10)
112.30(12)
113.10(11)
–
111.94(11)
109.88(13)
108.89(12)
110.73(12)
112.00(12)
103.03(13)
115.2(2)
–
[108.57(11)]
[110.30(12)]
[110.94(11)]
[112.21(11)]
[111.10(12)]
[103.70(12)]
[115.5(2)]
–
110.61(11)
110.54(12)
108.66(11)
113.21(11)
112.58(12)
100.83(10)
112.54(17)
113.36(18)
108.43(19)
111.11(16)
110.51(17)
115.9(2)
109.83(9)
110.63(9)
110.42(9)
109.27(9)
114.51(9)
101.94(9)
112.23(14)
111.76(13)
108.35(13)
113.53(13)
111.85(12)
112.29(15)
113.18(15)
–
C1–Si–C13
C1–Si–C16
C7–Si–C13
C7–Si–C16
C13–Si–C16
C14–N–C15
C14–N–C17
C15–N–C17
Si–C13–C14
Si–C16–C15
N–C14–C13
N–C15–C16
C14–N–C29
C15–N–C29
C17–N–C29
–
–
–
110.48(11)
110.54(10)
112.95(12)
112.32(13)
–
112.74(19)
110.48(19)
113.0(2)
112.6(2)
–
[110.31(16)]
[111.65(18)]
[111.7(2)]
[112.2(2)]
–
115.14(18)
106.56(19)
106.11(18)
109.56(17)
–
–
–
–
–
–
–
–
–
–
–
–
–
–
Fig. 1. Molecular structure of 5 in the crystal.
Fig. 2. Structure of the cation in the crystal of 6 Æ HCl.
The crystal structures of 6 Æ HCl, 13 Æ HCl, 15 Æ
HCl Æ 0.5EtOH, 17 Æ H2O, and 18 Æ HCl are governed
by hydrogen bonds [15]. In the case of 6 Æ HCl, the
cations and anions form intermolecular N–Hꢃ ꢃ ꢃCl
hydrogen bonds, resulting in the formation of infinite
chains along [100] (Fig. 9). Discrete ion pairs built up
by N–Hꢃ ꢃ ꢃCl hydrogen bonds are found in case of
hydrogen bonds, resulting in the formation of centro-
symmetric units consisting of two pairs of 4-silapipe-
ridinium cations, four chloride anions, and two
ethanol molecules (Fig. 10). For the hydrate
17 Æ H2O, intermolecular O–Hꢃ ꢃ ꢃO and O–Hꢃ ꢃ ꢃI
hydrogen bonds are found, by which the water mole-
cule connects the 4-silapiperidinium cation and the io-
dide anion (Fig. 11). Compound 18 Æ HCl forms
˚
˚
13 Æ HCl (N–H 0.933(18) A, Hꢃ ꢃ ꢃCl 2.139(18) A,
˚
Nꢃ ꢃ ꢃCl 3.0458(13) A, N–Hꢃ ꢃ ꢃCl 163.8(16)ꢁ), whereas
the crystal structure of 15 Æ HCl Æ 0.5EtOH is charac-
terized by intermolecular N–Hꢃ ꢃ ꢃCl and O–Hꢃ ꢃ ꢃCl

T. Heinrich et al. / Journal of Organometallic Chemistry 690 (2005) 33–47
39
Fig. 6. Structure of one of the two cations in the asymmetric unit in
the crystal of 15 Æ HCl Æ 0.5EtOH. The structure of the other cation
(not depicted) is very similar.
Fig. 3. Structure of the cation in the crystal of 8.
Fig. 4. Molecular structure of 9 in the crystal.
Fig. 7. Structure of the cation in the crystal of 17 Æ H2O.
3. Conclusions
In this study, a series of 4-silapiperidine and 4-sila-
piperidinium derivatives, with two silicon-bound aryl
groups and various N-organyl groups, were synthesized
and structurally characterized by solution NMR spectro-
scopy and single-crystal X-ray diffraction. These investi-
gations and the studies already reported in [6] provide
the basis for the development of further silicon-based
drugs containing a 4-silapiperidine or 4-silapiperidinium
skeleton. As demonstrated in [6], the silicon-bound aryl
groups can be removed with strong acids, such as
Fig. 5. Structure of the cation in the crystal of 13 Æ HCl.
discrete ion pairs, built by N–Hꢃ ꢃ ꢃCl hydrogen bonds
˚
˚
(N–H 1.02(2) A, Hꢃ ꢃ ꢃCl 2.01(2) A, Nꢃ ꢃ ꢃCl 3.0236(16)
˚
A, N–Hꢃ ꢃ ꢃCl 171.9(19)ꢁ).

40
T. Heinrich et al. / Journal of Organometallic Chemistry 690 (2005) 33–47
Fig. 11. Hydrogen-bonding system in the crystal of 17 Æ H2O. Selected
˚
distances (A) and angles (ꢁ): O3–H30 0.92(3), H30ꢃ ꢃ ꢃO2 2.25(3),
Fig. 8. Structure of the cation in the crystal of 18 Æ HCl.
O3ꢃ ꢃ ꢃO2 3.101(3), O3–H30ꢃ ꢃ ꢃO2 154(3); O3–H31 0.97(4), H31ꢃ ꢃ ꢃI
2.65(4), O3ꢃ ꢃ ꢃI 3.600(2), O3–H31ꢃ ꢃ ꢃI 169(3) [15]. The hydrogen atoms
(except for OH) are omitted for clarity.
trifluoromethanesulfonic acid, to generate Si-functional-
ized 4-silapiperidine and 4-silapiperidinium derivatives.
4. Experimental
4.1. Syntheses
4.1.1. General procedures
Fig. 9. Hydrogen-bonding system in the crystal of 6 Æ HCl. Selected
˚
All syntheses were carried out under dry nitrogen.
Acetone, acetonitrile, benzylamine, dichloromethane,
diethyl ether, dimethylformamide (DMF), ethanol,
methanol, n-pentane, 2-propanol, tetrahydrofuran
(THF), toluene, trichloromethane, and triethylamine
were dried and purified according to standard proce-
distances (A) and angles (ꢁ): NA–HA2 0.919(19), HA2ꢃ ꢃ ꢃClA
2.161(19), NAꢃ ꢃ ꢃClA 3.0574(15), NA–HA2ꢃ ꢃ ꢃClA 164.54(16); NB–
HB1 0.95(2), HB1ꢃ ꢃ ꢃClA 2.13(2), NBꢃ ꢃ ꢃClA 3.0766(13), NB–
HB1ꢃ ꢃ ꢃClA 175(2) [15]. The hydrogen atoms (except for NH) are
omitted for clarity.
dures and stored under nitrogen. A Buchi GKR 50
¨
apparatus was used for the bulb-to-bulb (Kugelrohr)
distillations. Melting points were determined with a
Buchi Melting Point B-540 apparatus using samples
¨
in open glass capillaries. 1H, 13C, 19F, and 29Si
NMR spectra were recorded at 22 ꢁC on a Bruker
DRX-300 NMR spectrometer (1H, 300.1 MHz; 13C,
75.5 MHz; 19F, 282.4 MHz; 29Si, 59.6 MHz) or a Bru-
ker AMX-400 NMR spectrometer (1H, 400.1 MHz;
13C, 100.6 MHz) using CDCl3, [D6]DMSO, or C6D6
as the solvent. Chemical shifts (ppm) were determined
relative to internal CHCl3 (1H, d 7.24; CDCl3), inter-
nal [D5]DMSO (1H, d 2.49; [D6]DMSO), internal
C6D5H (1H, d 7.28; C6D6), internal CDCl3 (13C, d
77.0; CDCl3), internal [D6]DMSO (13C,
d 39.5;
Fig. 10. Hydrogen-bonding system in the crystal of 15 Æ HCl Æ
˚
[D6]DMSO), internal C6D6 (13C, d 128.0; C6D6), exter-
nal CFCl3 (19F, d 0), or external TMS (29Si, d 0).
Analysis and assignment of the 1H NMR data were
0.5EtOH. Selected distances (A) and angles (ꢁ): O–H 0.84, Hꢃ ꢃ ꢃCl3
2.24, Oꢃ ꢃ ꢃCl3 3.077(5), O–Hꢃ ꢃ ꢃCl3 173; N–H1N 0.85(4), H1Nꢃ ꢃ ꢃCl30
2.43(4), Nꢃ ꢃ ꢃCl30 3.208(2), N–H1Nꢃ ꢃ ꢃCl30 153(4); N–H2N 1.00(4),
H2Nꢃ ꢃ ꢃCl3 2.12(4), Nꢃ ꢃ ꢃCl3 3.073(3), N–H2Nꢃ ꢃ ꢃCl3 161(3); N0–H1N0
0.83(4), H1N0ꢃ ꢃ ꢃCl30 2.32(4), N0ꢃ ꢃ ꢃCl30 3.143(3), N0–H1N0ꢃ ꢃ ꢃCl30
179(5); N0–H2N0 0.87(3), H2N0ꢃ ꢃ ꢃCl30A 2.35(4), N0ꢃ ꢃ ꢃCl30A
3.123(3), N0–H2N0ꢃ ꢃ ꢃCl30A 149(3) [15]. The hydrogen atoms (except
for NH and OH) are omitted for clarity.
1
supported by H,1H COSY and 29Si,1H COSY exper-
iments. Assignment of the 13C NMR data was sup-
ported by DEPT 135, 13C,1H HMQC, and 13C,1H
HMBC experiments.

T. Heinrich et al. / Journal of Organometallic Chemistry 690 (2005) 33–47
41
4.1.2. Diphenyldivinylsilane (2)
This compound was synthesized from commercially
available dichlorodiphenylsilane according to [9].
residue was then subjected to a Kugelrohr distillation
(220 ꢁC/0.01 mbar) to give 4 in 92% yield as an oily liq-
uid (13.7 g, 39.9 mmol). A solution of 4 and 2,2,2-tri-
chloroethyl chloroformate (10.0 g, 47.2 mmol) in THF
(100 ml) was then heated under reflux for 48 h. After
the mixture was cooled to 20 ꢁC, the volatile compo-
nents were removed by distillation in vacuo, and the oily
residue was dissolved in boiling 2-propanol. Slow cool-
ing of this solution to 20 ꢁC gave 5 in 78% yield as a col-
orless crystalline solid (14.5 g, 33.8 mmol); m.p. 121 ꢁC.
1H NMR (300.1 MHz, CDCl3): d 1.35–1.48 (m, 4H,
SiCH2CH2N), 3.70–3.86 (m, 4H, SiCH2CH2N), 4.78
(s, 2H, OCH2C), 7.31–7.48 (m, 6H, H-3/H-4/H-5,
SiC6H5), 7.49–7.58 (m, 4H, H-2/H-6, SiC6H5). 13C
4.1.3. Bis(2-bromoethyl)diphenylsilane (3)
This compound was synthesized from 2 according to
[1].
4.1.4. 1-Benzyl-4,4-diphenyl-4-silapiperidinium chloride
(4 Æ HCl)
Following the procedure given in [1], a mixture of 3
(30.0 g, 75.3 mmol), benzylamine (80.0 g, 747 mmol), tri-
ethylamine (23.0 g, 227 mmol), and trichloromethane
(700 ml) was heated under reflux for 16 h. After the mix-
ture was cooled to 20 ꢁC, water (500 ml) was added. The
organic phase was separated, the aqueous layer was ex-
tracted with trichloromethane (2 · 300 ml), the com-
bined organic extracts were dried over anhydrous
sodium sulfate, the solvent and the excess benzylamine
and triethylamine were removed under reduced pres-
sure, and the highly viscous residue was dissolved in ace-
tone (60 ml). A 2.0 M ethereal hydrogen chloride
solution (40.0 ml, 80.0 mmol of HCl) was added drop-
wise at 20 ꢁC, and the mixture was stirred at this temper-
ature for 24 h. The resulting precipitate was isolated by
filtration and recrystallized from 2-propanol (slow cool-
ing of a saturated boiling solution to 20 ꢁC) to give
4 Æ HCl in 75% yield as a colorless crystalline solid
(21.5 g, 56.6 mmol); m.p. 210 ꢁC. 1H NMR (300.1
NMR (75.5 MHz, CDCl3):
d
11.4 and 12.0
(SiCH2CH2N), 44.1 and 44.5 (SiCH2CH2N), 75.0
(OCH2C), 95.9 (CC Cl3), 128.2 (C-3/C-5, SiC6H5),
129.9 (C-4, SiC6H5), 134.46 (C-1, SiC6H5), 134.55 (C-
2/C-6, SiC6H5), 153.8 (CO). 29Si NMR (CDCl3): d
ꢀ14.4. Anal. Found: C, 53.2; H, 4.6; N, 2.9. Calc. for
C19H20Cl3NO2Si: C, 53.22; H, 4.70; N, 3.27%.
4.1.6. 4,4-Diphenyl-4-silapiperidinium chloride (6 Æ HCl)
A mixture of 5 (13.2 g, 30.8 mmol), zinc powder (10.0
g, 153 mmol), and acetic acid (100 ml) was stirred at 20
ꢁC for 48 h. The solid components were removed by fil-
tration, and the filtrate was concentrated under reduced
pressure to a volume of ca. 25 ml, followed by the addi-
tion of a 6 M aqueous sodium hydroxide solution (200
ml). The mixture was stirred at 20 ꢁC for 10 min and
was then extracted with diethyl ether (3 · 150 ml). The
combined organic extracts were dried over anhydrous
sodium sulfate, half of the solvent was removed under
reduced pressure, and a 2 M ethereal hydrogen chloride
solution (20.0 ml, 40.0 mmol of HCl) was added to the
stirred mixture at 20 ꢁC. The resulting precipitate was
isolated by filtration and recrystallized from ethanol
(slow cooling of a saturated boiling solution to 20 ꢁC)
to give 6 Æ HCl in 84% yield as a colorless crystalline so-
lid (7.50 g, 25.9 mmol); m.p. 223–224 ꢁC. 1H NMR
(300.1 MHz, CDCl3): d 1.65–1.81 (m, 4H, SiCH2CH2N),
3.33–3.50 (m, 4H, SiCH2CH2N), 7.33–7.47 (m, 6H, H-3/
H-4/H-5, SiC6H5), 7.50–7.58 (m, 4H, H-2/H-6, SiC6H5),
9.6 (br s, 2H, NH2). 13C NMR (75.5 MHz, CDCl3): d 9.0
(SiCH2CH2N), 44.1 (SiCH2CH2N), 128.4 (C-3/C-5,
SiC6H5), 130.4 (C-4, SiC6H5), 131.8 (C-1, SiC6H5),
134.6 (C-2/C-6, SiC6H5). 29Si NMR (CDCl3): d ꢀ16.6.
Anal. Found: C, 66.2; H, 6.8; N, 4.8. Calc. for
C16H20ClNSi: C, 66.30; H, 6.95; N, 4.83%.
MHz, [D6]DMSO):
d
1.55–1.70 (m, 2H, Si-
CHAHBCH2N), 1.81–1.98 (m, 2H, SiCHAHBCH2N),
2.90–3.08 (m, 2H, SiCH2CHAHBN), 3.53–3.67 (m, 2H,
SiCH2CHAHBN), 4.31 (d, 2JHH = 5.2 Hz, 2H,
NCH2C6H5), 7.32–7.54 and 7.65–7.73 (m, 15H, SiC6H5,
CH2C6H5), 11.4 (br s, 1H, NH). 13C NMR (75.5 MHz,
[D6]DMSO): d 7.7 (SiC2CH2N), 51.2 (SiCH2CH2N),
58.8 (NCH2C6H5), 128.1 (C-3/C-5, SiC6H5), 128.4 (C-
30/C-50, SiC6H5), 128.7 (C-2/C-6, CH2C6H5), 129.3 (C-
4, CH2C6H5), 130.0 (C-4, SiC6H5), 130.2 (C-40, SiC6H5),
130.4 (C-1, CH2C6H5), 131.4 (C-3/C-5, CH2C6H5),
131.5 (C-1, SiC6H5), 133.8 (C-10, SiC6H5), 134.3 (C-2/
C-6, SiC6H5), 134.7 (C-20/C-60, SiC6H5). 29Si NMR
([D6]DMSO): d ꢀ17.4. Anal. Found: C, 72.1; H, 6.9;
N, 3.7. Calc. for C23H26ClNSi: C, 72.70; H, 6.90; N,
3.69%.
4.1.5. 2,2,2-Trichloroethyl 4,4-diphenyl-4-silapiperidine-
1-carboxylate (5)
Compound 4 Æ HCl (16.5 g, 43.4 mmol) was added at
20 ꢁC to a mixture of a 2 M aqueous sodium hydroxide
solution (60 ml) and diethyl ether (80 ml), and the result-
ing mixture was stirred at 20 ꢁC for 30 min. The organic
phase was separated, the aqueous layer was extracted
with diethyl ether (2 · 100 ml), and the combined organic
extracts were dried over anhydrous sodium sulfate. The
solvent was removed under reduced pressure, and the
4.1.7. 1-{3-[2-(4-Fluorophenyl)-1,3-dioxolan-2-yl]pro-
pyl}-4,4-diphenyl-4-silapiperidine (7)
Method A: A mixture of 3 (5.00 g, 12.6 mmol),
3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propylamine [12]
(3.40 g, 15.1 mmol), triethylamine (3.00 g, 29.6 mmol),
acetonitrile (30 ml), and toluene (30 ml) was heated in

42
T. Heinrich et al. / Journal of Organometallic Chemistry 690 (2005) 33–47
a 250-ml autoclave at 90 ꢁC for 16 h. After the mixture
was cooled to 20 ꢁC, the precipitate was removed by fil-
tration, and water (60 ml) was added to the filtrate. The
organic phase was separated, the aqueous layer was
extracted with toluene (2 · 50 ml), and the combined or-
ganic extracts were dried over anhydrous sodium sul-
fate. The solvent was removed under reduced pressure,
and the residue was then subjected to a Kugelrohr distil-
lation (250 ꢁC/0.01 mbar) to give 8 in 67% yield as a
highly viscous liquid (3.90 g, 8.45 mmol). 1H NMR
(300.1 MHz, CDCl3): d 1.25–1.40 (m, 4H, SiCH2CH2N),
1.47–1.62 (m, 2H, NCH2CH2CH2C), 1.80–1.92 (m, 2H,
NCH2CH2CH2C), 2.36–2.47 (m, 2H, NCH2CH2CH2C),
2.73–2.86 (m, 4H, SiCH2CH2N), 3.68–3.80 and 3.93–
4.06 (m, 4H, OCH2CH2O), 6.95–7.05 (m, 2H, H-3/H-
5, CC6H4F), 7.30–7.47 (m, 8H, H-3/H-4/H-5, SiC6H5,
H-2/H-6, CC6H4F), 7.48–7.56 (m, 4H, H-2/H-6,
SiC6H5). 13C NMR (75.5 MHz, CDCl3): d 11.0 (SiCH2-
CH2N), 21.2 (NCH2CH2CH2C), 38.5 (NCH2CH2-
CH2C), 52.1 (SiCH2CH2N), 57.9 (NCH2CH2CH2C),
64.5 (OCH2CH2O), 110.1 (C2CO2), 114.9 (d,
2JCF = 21.4 Hz, C-3/C-5, CC6H4F), 127.5 (d,
3JCF = 8.4 Hz, C-2/C-6, CC6H4F), 127.9 (C-3/C-5,
SiC6H5), 129.4 (C-4, SiC6H5), 134.7 (C-2/C-6, SiC6H5),
duced pressure, and the residue was then subjected
to a Kugelrohr distillation (250 ꢁC/0.01 mbar) to give
7 in 42% yield as a highly viscous liquid (2.70 g, 5.85
mmol). C28H32FNO2Si. The NMR-spectroscopic data
of the product were identical with those obtained for
the product synthesized according to Method A. An
elemental analysis was not performed because of the
high viscosity of the product; instead, the methylam-
monium iodide 8 was analyzed (see below).
4.1.8. 1-{3-[2-(4-Fluorophenyl)-1,3-dioxolan-2-yl]pro-
pyl}-1-methyl-4,4-diphenyl-4-silapiperidinium iodide (8)
Methyl iodide (1.54 g, 10.8 mmol) was added at 20 ꢁC
to a solution of 7 (1.00 g, 2.17 mmol) in acetone (20 ml),
and the resulting mixture was stirred at 20 ꢁC for 24 h.
The solvent and the excess methyl iodide were removed
under reduced pressure, and the solid residue was dried
in vacuo and then recrystallized from ethanol/ethyl ace-
tate (2:1 (v/v)) (slow cooling of a saturated boiling solu-
tion to 0 ꢁC) to give 8 in 88% yield as a colorless
crystalline solid (1.15 g, 1.91 mmol); m.p. 186–187 ꢁC.
1H NMR (300.1 MHz, CDCl3): d 1.51–1.75 (m, 4H,
SiCH2CH2N), 1.78–2.03 (m, 4H, NCH2CH2CH2C,
NCH2CH2CH2C), 3.34 (s, 3H, NCH3), 3.57–4.04 (m,
10H, OCH2CH2O, SiCH2CH2N, NCH2CH2CH2C),
6.89–6.98 (m, 2H, H-3/H-5, CC6H4F), 7.27–7.55 (m,
12H, SiC6H5, H-2/H-6, CC6H4F). 13C NMR (75.5
MHz, CDCl3): d 6.7 (SiCH2CH2N), 16.5 (NCH2CH2-
CH2C), 36.0 (NCH2CH2CH2C), 50.1 (NCH3), 60.7
(NCH2CH2-CH2C), 61.1 (SiCH2CH2N), 64.4 (OCH2-
4
135.6 (C-1, SiC6H5), 138.5 (d, JCF = 2.9 Hz, C-1,
1
CC6H4F), 162.4 (d, JCF = 245.6 Hz, C-4, CC6H4F).
19F NMR (CDCl3): d ꢀ115.5. 29Si NMR (CDCl3): d
ꢀ15.3. C28H32FNO2Si. An elemental analysis was not
performed because of the high viscosity of the product;
instead, the methylammonium iodide 8 was analyzed
(see below).
2
CH2O), 109.0 (C2CO2), 115.1 (d, JCF = 21.4 Hz, C-3/
3
Method B: Compound 6 Æ HCl (4.00 g, 13.8 mmol)
was added at 20 ꢁC to a mixture of a 2 M aqueous
sodium hydroxide solution (30 ml) and diethyl ether
(40 ml), and the resulting mixture was stirred at 20
ꢁC for 30 min. The organic phase was separated, the
aqueous layer was extracted with diethyl ether
(2 · 50 ml), and the combined organic extracts were
dried over anhydrous sodium sulfate. The solvent
was removed under reduced pressure, and the residue
was then subjected to a Kugelrohr distillation (180ꢁC/
0.01 mbar) to give 6 in 95% yield as an oily liquid
(3.29 g, 13.1 mmol). A mixture of 6, 2-(3-chloropro-
pyl)-2-(4-fluorophenyl)-1,3-dioxolane (3.20 g, 13.1
mmol), potassium iodide (500 mg, 3.01 mmol), potas-
sium carbonate (2.50 g, 18.1 mmol), and acetonitrile
(60 ml) was heated in a 250-ml autoclave at 100 ꢁC
for 18 h. After the mixture was cooled to 20 ꢁC, the
precipitate was separated by filtration, and the solvent
of the filtrate was removed under reduced pressure,
followed by the addition of a 0.1 M aqueous sodium
hydroxide solution (60 ml) and diethyl ether (100 ml).
The organic phase was separated, the aqueous layer
was extracted with diethyl ether (2 · 50 ml), and the
combined organic extracts were dried over anhydrous
sodium sulfate. The solvent was removed under re-
C-5, CC6H4F), 127.3 (d, JCF = 8.4 Hz, C-2/C-6,
CC6H4F), 128.6 (C-3/C-5, SiC6H5), 128.7 (C-30/C-50,
SiC6H5), 130.6 (C-1, SiC6H5), 130.78 (C-4, SiC6H5),
130.80 (C-40, SiC6H5), 131.2 (C-10, SiC6H5), 134.2
(C-2/C-6, SiC6H5), 134.4 (C-20/C-60, SiC6H5), 137.5 (d,
1
4JCF = 2.9 Hz, C-1, CC6H4F), 162.5 (d, JCF = 246.7
Hz, C-4, CC6H4F). 19F NMR (CDCl3): d ꢀ114.5. 29Si
NMR (CDCl3): d ꢀ22.1. Anal. Found: C, 57.5; H, 5.8;
N, 2.4. Calc. for C29H35FINO2Si: C, 57.71; H, 5.84;
N, 2.32%.
4.1.9. 1-[4-Oxo-4-(4-fluorophenyl)butyl]-4,4-diphenyl-4-
silapiperidine (9)
2 M hydrochloric acid (2 ml) was added to a solu-
tion of 7 (1.50 g, 3.25 mmol) in acetone (20 ml), and
the mixture was then heated at 60 ꢁC for 2 h. After
the mixture was cooled to 20 ꢁC, a 6 M aqueous so-
dium hydroxide solution (6 ml) and toluene (40 ml)
were added. The organic phase was separated, the
aqueous layer was extracted with toluene (2 · 50 ml),
and the combined organic extracts were dried over
anhydrous sodium sulfate. The solvent was removed
under reduced pressure, the residue was dissolved in
2-propanol (7 ml), and the resulting solution was then
kept undisturbed at ꢀ20 ꢁC for three days to give 9 in

T. Heinrich et al. / Journal of Organometallic Chemistry 690 (2005) 33–47
43
88% yield as a colorless crystalline solid (1.20 g, 2.87
1
CHAHBCH2N), 1.82–2.00 (m, 2H, SiCHAHBCH2N),
2.90–3.08 (m, 2H, SiCH2CHAHBN), 3.52–3.67 (m,
mmol); m.p. 82 ꢁC. H NMR (300.1 MHz, CDCl3): d
3
2H, SiCH2CHAHBN), 4.30 (d, JHH = 5.2 Hz, 2H,
1.27–1.45 (m, 4H, SiCH2CH2N), 1.90–2.06 (m, 2H,
NCH2CH2CH2C), 2.50–2.63 (m, 2H, NCH2CH2-
CH2C), 2.80–2.97 (m, 4H, SiCH2CH2N), 2.98 (t,
3JHH = 6.9 Hz, 2H, NCH2CH2CH2C), 7.06–7.14 (m,
2H, H-3/H-5, CC6H4F), 7.31–7.42 (m, 6H, H-3/H-4/
H-5, SiC6H5), 7.47–7.53 (m, 4H, H-2/H-6, SiC6H5),
7.95–8.03 (m, 2H, H-2/H-6, CC6H4F). 13C NMR
NCH2C6H5), 7.37–7.58 and 7.62–7.78 (m, 13H,
SiC6H4Cl, CC6H5), 11.5 (br s, 1H, NH). 13C NMR
(75.5 MHz, [D6]DMSO): d 7.6 (SiCH2CH2N), 51.0
(SiCH2CH2N), 58.9 (NCH2CH2CH2C), 128.2 (C-3/C-
5, SiC6H4Cl), 128.5 (C-30/C-50, SiC6H4Cl), 128.7 (C-
2/C-6, CC6H5), 129.3 (C-4, CC6H5), 130.1 (C-1,
SiC6H4Cl), 130.4 (C-1, CC6H5), 131.4 (C-3/C-5,
CC6H5), 132.4 (C-10, SiC6H4Cl), 135.5 (C-4,
SiC6H4Cl), 135.7 (C-40, SiC6H4Cl), 136.2 (C-2/C-6,
SiC6H4Cl), 136.7 (C-20/C-60, SiC6H4Cl). 29Si NMR
([D6]DMSO): d ꢀ16.3. Anal. Found: C, 61.2; H, 5.5;
N, 3.1. Calc. for C23H24Cl3NSi: C, 61.54; H, 5.39;
N, 3.12%.
(75.5 MHz, CDCl3):
d 10.7 (SiCH2CH2N), 21.7
(NCH2CH2CH2C), 36.2 (NCH2CH2CH2C), 52.3
(SiCH2CH2N), 57.0 (NCH2CH2CH2C), 115.6 (d,
2JCF = 21.8 Hz, C-3/C-5, CC6H4F), 130.7 (d,
3JCF = 9.1 Hz, C-2/C-6, CC6H4F), 128.0 (C-3/C-5,
4
SiC6H5), 129.6 (C-4, SiC6H5), 133.6 (d, JCF = 3.3
Hz, C-1, CC6H4F), 134.7 (C-1/C-2/C-6, SiC6H5),
1
165.7 (d, JCF = 254.3 Hz, C-4, CC6H4F), 198.4
(CO). 19F NMR (CDCl3): d ꢀ106.1. 29Si NMR
(CDCl3): d ꢀ15.6. Anal. Found: C, 74.6; H, 6.8; N,
3.1. Calc. for C26H28FNOSi: C, 74.78, H, 6.76; N,
3.35%.
4.1.14. 4,4-Bis(4-chlorophenyl)-4-silapiperidinium chlo-
ride–semiethanol (15 Æ HCl Æ 0.5EtOH)
Compound 13 Æ HCl (2.50 g, 5.57 mmol) was added at
20 ꢁC to a mixture of a 2 M aqueous sodium hydroxide
solution (25 ml) and diethyl ether (50 ml), and the result-
ing mixture was stirred at 20 ꢁC for 30 min. The organic
phase was separated, the aqueous layer was extracted with
diethyl ether (2 · 50 ml), and the combined organic ex-
tracts were dried over anhydrous sodium sulfate. The sol-
vent was removed under reduced pressure, and the residue
was then subjected to a Kugelrohr distillation (220 ꢁC/
0.002 mbar) to give 13 in 91% yield as an oily liquid
(2.10 g, 5.09 mmol). 1-Chloroethyl chloroformate (750
mg, 5.25 mmol) was added dropwise within 5 s at 0 ꢁC
to a stirred solution of 13 in trichloromethane (30 ml).
The mixture was stirred at 0 ꢁC for 10 min and then at
65 ꢁC for a further 50 min. After the mixture was cooled
to 20 ꢁC, the solvent was removed under reduced pressure,
and the residue (1-chloroethyl-4,4-bis(4-chlorophenyl)-4-
silapiperidine-1-carboxylate (14; crude product, not puri-
fied)) was dissolved in methanol (20 ml), and the resulting
solution was stirred under reflux for 60 min (formation of
a precipitate). Approximately 10 ml of the methanol were
distilled off, and the mixture was then kept undisturbed at
ꢀ20 ꢁC for 24 h. The precipitate was isolated by filtration
and recrystallized from ethanol (slow cooling of a satu-
rated boiling solution to 20 ꢁC) to give 15 Æ HCl Æ 0.5EtOH
in 68% yield as a colorless crystalline solid (1.45 g, 3.80
4.1.10. Bis(4-chlorophenyl)dimethoxysilane (10)
This compound was prepared from tetramethoxysi-
lane according to [6].
4.1.11. Bis(4-chlorophenyl)divinylsilane (11)
This compound was prepared from 10 according to
[6].
4.1.12. Bis(2-bromoethyl)bis(4-chlorophenyl)silane (12)
This compound was prepared from 11 according to
[6].
4.1.13. 1-Benzyl-4,4-bis(4-chlorophenyl)-4-silapiperidi-
nium chloride (13 Æ HCl)
A mixture of 12 (5.00 g, 10.7 mmol), benzylamine
(14.9 g, 139 mmol), triethylamine (3.00 g, 29.6 mmol),
and trichloromethane (100 ml) was heated under re-
flux for 16 h. After the mixture was cooled to 20
ꢁC, water (100 ml) was added. The organic phase
was separated, the aqueous layer was extracted with
trichloromethane (2 · 50 ml), the combined organic
extracts were dried over anhydrous sodium sulfate,
the solvent and the excess benzylamine and triethyl-
amine were removed under reduced pressure, and the
highly viscous residue was dissolved in acetone (5
ml). A 2.0 M ethereal hydrogen chloride solution
(6.0 ml, 12.0 mmol of HCl) was added dropwise at
20 ꢁC, and the mixture was stirred at this temperature
for 24 h. The resulting precipitate was isolated by fil-
tration and recrystallized from 2-propanol by slow
evaporation of the solvent at 20 ꢁC to give 13 Æ HCl
in 65% yield as a colorless crystalline solid (3.10 g,
6.91 mmol); m.p. 220–221 ꢁC (dec.). 1H NMR
(300.1 MHz, [D6]DMSO): d 1.57–1.73 (m, 2H, Si-
1
mmol); m.p. 261–262 ꢁC (dec.). H NMR (400.1 MHz,
3
CDCl3): d 1.44 (t, JHH = 7.0 Hz, 1.5H, CH3CH2OH),
1.90–2.00 (m, 4H, SiCH2CH2N), 2.8 (br s, 0.5H,
CH3CH2OH), 3.57–3.69 (m, 4H, SiCH2CH2N), 3.92 (q,
3JHH = 7.0 Hz, 1H, CH3CH2OH), 7.58–7.63 and 7.66–
7.71 (m, 8H, SiC6H4Cl), 9.9 (br s, 2H, NH2). 13C NMR
(100.6 MHz, CDCl3):
d 8.8 (SiCH2CH2N), 18.3
(CH3CH2OH), 44.1 (SiCH2CH2N), 58.3 (CH3CH2OH)
128.9 (C-3/C-5, SiC6H4Cl), 129.7 (C-1, SiC6H4Cl), 135.9
(C-2/C-6, SiC6H4Cl), 137.2 (C-4, SiC6H4Cl). 29Si NMR

44
T. Heinrich et al. / Journal of Organometallic Chemistry 690 (2005) 33–47
(CDCl3): d ꢀ16.0. Anal. Found: C, 53.3; H, 5.5; N, 3.7.
m.p. 172–174 ꢁC. Anal. Found: C, 50.7; H, 4.9; N, 2.0.
Calc. for C29H35Cl2FINO3Si: C, 50.44; H, 5.11; N,
2.03%.
Calc. for C17H21Cl3NO0.5Si: C, 53.48; H, 5.54; N, 3.67%.
4.1.15.
4,4-Bis(4-chlorophenyl)-1-{3-[2-(4-fluorophe-
4.1.16.
4,4-Bis(4-chlorophenyl)-1-{3-[2-(4-fluorophe-
nyl)-1,3-dioxolan-2-yl]propyl}-1-methyl-4-silapiperidi-
nium iodide (17) and hydrate 17 Æ H2O
nyl)-1,3-dithian-2-yl]propyl}-4-silapiperidinium chloride
(18 Æ HCl)
A mixture of 12 (5.00 g, 10.7 mmol), 3-[2-(4-fluoro-
phenyl)-1,3-dioxolan-2-yl]propylamine [12] (2.50 g,
11.1 mmol), triethylamine (3.00 g, 29.6 mmol), acetonit-
rile (30 ml), and toluene (30 ml) was heated in a 250-ml
autoclave at 90 ꢁC for 16 h. After the mixture was
cooled to 20 ꢁC, the precipitate was removed by filtra-
tion, and water (60 ml) was added to the filtrate. The or-
ganic phase was separated, the aqueous layer was
extracted with toluene (2 · 50 ml), and the combined or-
ganic extracts were dried over anhydrous sodium sul-
fate. The solvent and the excess triethylamine were
removed under reduced pressure, and the residue (4,4-
bis(4-chlorophenyl)-1-{3-[2-(4-fluorophenyl)-1,3-dioxo-
lan-2-yl]propyl}-4-silapiperidine (16; crude product, not
purified)) was dissolved in acetone (30 ml), followed by
the addition of methyl iodide (3.60 g, 25.4 mmol). The
resulting mixture was stirred at 20 ꢁC for 24 h, the sol-
vent and the excess methyl iodide were removed under
reduced pressure, and the solid residue was dried in va-
cuo and then recrystallized from ethanol (slow cooling
of a saturated boiling solution to 20 ꢁC) to give 17 in
62% yield as a colorless crystalline solid (4.45 g, 6.62
mmol); m.p. 168–169 ꢁC. 1H NMR (300.1 MHz,
A mixture of 12 (7.20 g, 15.4 mmol), 19 (4.20 g, 15.5
mmol), triethylamine (4.50 g, 44.5 mmol), acetonitrile
(50 ml), and toluene (50 ml) was heated in a 250-ml auto-
clave at 90 ꢁC for 40 h. After the mixture was cooled to
ꢀ20 ꢁC, the precipitate was removed by filtration, and
water (60 ml) was added to the filtrate. The organic phase
was separated, the aqueous layer was extracted with tolu-
ene (2 · 50 ml), the combined organic extracts were dried
over anhydrous sodium sulfate, and the solvent was re-
moved under reduced pressure. The residue was dissolved
in diethyl ether (40 ml), and the solution was cooled to
ꢀ20 ꢁC, followed by dropwise addition of a 2.0 M ethereal
hydrogen chloride solution (10 ml, 20.0 mmol of HCl).
The mixture was stirred at ꢀ20 ꢁC for 10 min, and the pre-
cipitate was isolated by filtration, washed with diethyl
ether (2 20 ml), and recrystallized from methanol (slow
cooling of a saturated boiling solution to 20 ꢁC) to give
18 Æ HCl in 71% yield as a colorless crystalline solid
1
(6.70 g, 10.9 mmol); m.p. 233–234 ꢁC (dec.). H NMR
(300.1 MHz, [D6]DMSO): d 1.50–1.71 and 1.72–
1.97 (m, 8H, SiCH2CH2N, NCH2CH2CH2C,
SCH2CH2CH2S), 2.05–2.25 (m, 2H, NCH2CH2CH2C),
2.48–2.68 (m, 2H, SCHAHBCH2CHAHBS), 2.80–3.15
(m, 6H, SCHAHBCH2CHAHBS, SiCH2CHAHBN,
NCH2CH2 CH2C), 3.35–3.60 (m, 2H, SiCH2CHAHBN),
7.15–7.30 (m, 2H, H-3/H-5, CC6H4F), 7.40–7.60 and
7.63–7.85 (m, 10H, H-2/H-3/H-5/H-6, SiC6H4Cl, H-2/
H-6, CC6H4F), 10.9 (br s, 1H, NH). 13C NMR (75.5
MHz, [D6]DMSO): d 7.3 (SiCH2CH2N), 19.3 (NCH2CH2
CH2C), 24.3 (SCH2CH2CH2S), 26.8 (SC2CH2CH2S),
39.3 (NCH2CH2CH2C), 51.3 (SiCH2CH2N), 54.7
[D6]DMSO):
d
1.52–1.78 (m, 6H, SiCH2CH2N,
NCH2CH2CH2C), 1.84–1.95 (m, 2H, NCH2CH2CH2C),
3.00 (s, 3H, NCH3), 3.30–3.63 (m, 6H, SiCH2CH2N,
NCH2CH2CH2C), 3.62–3.74 and 3.91–4.06 (m, 4H,
OCH2CH2O), 7.12–7.23 (m, 2H, H-3/H-5, CC6H4F),
7.38–7.47 (m, 2H, H-2/H-6, CC6H4F), 7.47–7.55 (m,
4H, H-3/H-5, SiC6H4Cl), 7.57–7.73 (m, 4H, H-2/H-6,
SiC6H4Cl). 13C NMR (75.5 MHz, [D6]DMSO): d 5.3
(SiCH2CH2N), 16.0 (NCH2CH2CH2C), 36.1 (NCH2
CH2CH2C), 48.6 (NCH3), 59.4 (NCH2CH2CH2C),
59.4 (SiCH2CH2N), 64.3 (OCH2CH2O), 108.8
2
(NC2CH2CH2C), 56.5 (C2CS2), 115.3 (d, JCF = 21.4
Hz, C-3/C-5, CC6H4F), 128.2 (C-3/C-5, SiC6H4Cl),
128.4 (C-30/C-50, SiC6H4Cl), 130.1 (d, 3JCF = 8.0 Hz, C-
2/C-6, CC6H4F), 130.3 (C-1, SiC6H4Cl), 132.2 (C-10,
SiC6H4Cl), 135.5 (C-4, SiC6H4Cl), 135.6 (C-40, Si-
C6H4Cl), 136.2 (C-2/C-6, SiC6H4Cl), 136.6 (C-20/C-60,
2
(C2CO2), 115.0 (d, JCF = 21.4 Hz, C-3/C-5, CC6H4F),
3
127.5 (d, JCF = 8.0 Hz, C-2/C-6, CC6H4F), 128.3 (C-
3/C-5, SiC6H4Cl), 128.4 (C-30/C-50, SiC6H4Cl), 130.7
(C-1, SiC6H4Cl), 131.2 (C-10, SiC6H4Cl), 135.6 (C-4,
SiC6H4Cl), 135.7 (C-40, SiC6H4Cl), 136.4 (C-2/C-6,
SiC6H4Cl), 136.5 (C-20/C-60, SiC6H4Cl), 138.4 (d,
4
SiC6H4Cl), 137.5 (d, JCF = 2.9 Hz, C-1, CC6H4F),
1
161.1 (d, JCF = 244.9 Hz, C-4, CC6H4F). 19F NMR
([D6]DMSO): d ꢀ115.9. 29Si NMR ([D6]DMSO): d
ꢀ16.6. Anal. Found: C, 56.4; H, 5.4; N, 2.3; S 10.4. Calc.
for C29H33Cl3FNS2Si: C, 56.81; H, 5.42; N, 2.28; S,
10.46%.
1
4JCF = 2.9 Hz, C-1, CC6H4F), 161.8 (d, JCF = 243.8
Hz, C-4, CC6H4F). 19F NMR ([D6]DMSO): d ꢀ115.1.
29Si NMR ([D6]DMSO): d ꢀ19.1. Anal. Found: C,
51.7; H, 5.0; N, 2.1%. Calc. for C29H33Cl2FINO2Si
(Mr = 672.47): C, 51.80; H, 4.95; N, 2.08%. Crystalliza-
tion of the product (1.00 g, 1.49 mmol) from ethanol/
ethyl acetate/water (2:1:0.1 (v/v/v)) by slow evaporation
of the solvent at 20 ꢁC gave the hydrate 17 Æ H2O in 85%
yield as a colorless crystalline solid (870 mg, 1.26 mmol);
4.1.17. 3-[2-(4-Fluorophenyl)-1,3-dithian-2-yl]propyl-
amine (19)
A mixture of 21 (7.50 g, 18.7 mmol), hydrazine hy-
drate (10.0 g, 200 mmol), and ethanol (500 ml) was

T. Heinrich et al. / Journal of Organometallic Chemistry 690 (2005) 33–47
45
heated under reflux for 3 h. After the mixture was cooled
to 20 ꢁC, the precipitate was filtered off and discarded,
and the solvent of the filtrate was removed under re-
duced pressure. Diethyl ether (150 ml) and a half-
saturated aqueous sodium carbonate solution (10 ml)
were added to the solid residue, and the mixture was
stirred at 20 ꢁC for 10 min. The organic phase was sep-
arated, the aqueous layer was extracted with diethyl
ether (2 · 100 ml), the combined organic extracts were
dried over anhydrous sodium sulfate, and the solvent
was removed under reduced pressure to give 19 in 78%
yield as a yellowish, highly viscous oily liquid (3.95 g,
14.6 mmol). (This product was used for the synthesis
of 18 Æ HCl without further purification.) 1H NMR
(400.1 MHz, C6D6): d 0.9 (br s, 2H, NH2), 1.42–1.55
(m, 3H, NCH2CH2CH2C, SCH2CHAHBCH2S), 1.71–
1.85 (m, 1H, SCH2CHAHBCH2S), 2.10–2.19 (m, 2H,
NCH2CH2CH2C), 2.28–2.50 (m, 6H, SCH2CH2CH2S,
NCH2CH2CH2C), 6.96–7.04 (m, 2H, H-3/H-5,
CC6H4F), 7.94–8.01 (m, H-2/H-6, CC6H4F). 13C NMR
(100.6 MHz, C6D6): d 25.4 (SCH2CH2CH2S), 27.6
(SCH2CH2CH2S), 28.4 (NCH2CH2CH2C), 42.2
(NCH2CH2CH2C), 43.1 (NCH2CH2CH2C), 58.7
4.1.19. 2-(3-Chloropropyl)-2-(4-fluorophenyl)-1,3-dithi-
ane (20)
A mixture of 4-chloro-1-(4-fluorophenyl)butan-1-
one (15.0 g, 74.8 mmol), propane-1,3-dithiol (10.0 g,
92.4 mmol), and a 2.0 M ethereal hydrogen chloride
solution (90 ml, 180 mmol of HCl) was stirred at 20
ꢁC for three days and then cooled to 0 ꢁC, followed
by the addition of water (100 ml). The organic phase
was separated, washed with water (2 · 100 ml), and
dried over anhydrous sodium sulfate. The solvent
and the excess propane-1,3-dithiol were removed un-
der reduced pressure (crystallization of the residue
upon standing at 20 ꢁC), and the resulting solid was
washed with methanol (50 ml) and then recrystallized
from n-pentane (slow cooling of a saturated boiling
solution to 20 ꢁC) to give 20 in 82% yield as a color-
less crystalline solid (17.8 g, 61.2 mmol); m.p. 53–54
ꢁC. 1H NMR (300.1 MHz, CDCl3): d 1.66–1.78
(m, 2H, ClCH2CH2CH2C), 1.84–2.02 (m, 2H,
SCH2CH2CH2S), 2.08–2.18 (m, 2H, NCH2CH2CH2C),
3
2.60–2.74 (m, 4H, SCH2CH2CH2S), 3.39 (t, JHH = 6.4
Hz, 2H, ClCH2CH2CH2C), 6.98–7.09 (m, 2H, H-3/H-
5, CC6H4F), 7.80–7.90 (m, 2H, H-2/H-6, CC6H4F).
2
(C2CS2), 115.3 (d, JCF = 21.0 Hz, C-3/C-5, CC6H4F),
3
131.2 (d, JCF = 8.1 Hz, C-2/C-6, CC6H4F), 138.5 (d,
13C NMR (75.5 MHz, CDCl3):
d 25.0 (SCH2
CH2CH2S), 27.2 (ClCH2CH2CH2C), 27.5 (SCH2CH2
CH2S), 42.3 (NCH2CH2CH2C), 44.7 (ClCH2CH2CH2
1
4JCF = 2.9 Hz, C-1, CC6H4F), 162.0 (d, JCF = 246.5
Hz, C-4, CC6H4F). 19F NMR (C6D6): d ꢀ116.2.
C13H18FNS2. An elemental analysis was not performed
because of the high viscosity of the product. Instead, the
hydrochloride 19 Æ HCl was analyzed (see below).
2
C), 57.6 (C2CS2), 115.3 (d, JCF = 21.1 Hz, C-3/C-5,
3
CC6H4F), 130.5 (d, JCF = 8.0 Hz, C-2/C-6, CC6H4F),
4
137.2 (d, JCF = 3.3 Hz, C-1, CC6H4F), 161.7
(1JCF = 247.1 Hz, C-4, CC6H4F). 19F NMR (CDCl3):
d ꢀ115.8. Anal. Found: C, 53.9; H, 5.5; S, 22.0. Calc.
for C13H16ClFS2: C, 53.68; H, 5.54; S, 22.05%.
4.1.18. 3-[2-(4-Fluorophenyl)-1,3-dithian-2-yl]propyl-
ammonium chloride (19 Æ HCl)
4.1.20. 2-{3-[2-(4-Fluorophenyl)-1,3-dithian-2-yl]pro-
pyl}phthalimide (21)
A 2.0 M ethereal hydrogen chloride solution (1 ml,
2.00 mmol of HCl) was added dropwise to a stirred
cooled solution (–20 ꢁC) of 6 (500 mg, 1.84 mmol) in
diethyl ether (10 ml). The mixture was stirred at ꢀ20
ꢁC for 10 min, and the precipitate was isolated by filtra-
tion to give 19 Æ HCl in 96% yield as a colorless crystal-
A mixture of 20 (11.0 g, 37.8 mmol), phthalimide
(6.00 g, 40.8 mmol), 1,8-diazabicyclo[5.4.0]undec-7-
ene (5.80 g, 38.1 mmol), and DMF (80 ml) was stirred
at 45 ꢁC for three days. The mixture was then cooled
to 20 ꢁC, and water (100 ml), dichloromethane (150
ml), and 0.1 M hydrochloric acid (20 ml) were added.
The organic phase was separated, the aqueous layer
was extracted with dichloromethane (2 · 100 ml),
and the combined organic extracts were washed with
water (100 ml) and then dried over anhydrous sodium
sulfate. The solvent was removed under reduced pres-
sure, and the residue was redissolved in diisopropyl
ether (40 ml) (formation of a precipitate at 20 ꢁC
within 2 h). The product was isolated by filtration
and recrystallized from ethyl acetate (slow cooling of
a saturated boiling solution to 20 ꢁC) to give 21 in
72% yield as a colorless solid (10.9 g, 27.1 mmol);
m.p. 128–129 ꢁC. 1H NMR (300.1 MHz, CDCl3):
1
line solid (545 mg, 1.77 mmol); m.p. 168–169 ꢁC. H
NMR (300.1 MHz, [D6]DMSO): d 1.38–1.54 (m, 2H,
NCH2CH2CH2C), 1.75–1.93 (m, 2H, SCH2CH2CH2S),
2.06–2.22 (m, 2H, NCH2CH2CH2C), 2.50–2.77 and
2.80–2.95 (m, 6H, SCH2CH2CH2S, NCH2CH2CH2C),
7.17–7.28 (m, 2H, H-3/H-5, CC6H4F), 7.72–7.83 (m,
H-2/H-6, CC6H4F), 8.0 (br s, 3H, NH3). 13C NMR
(75.5 MHz, [D6]DMSO): d 22.5 (NCH2CH2CH2C),
24.5 (SCH2CH2CH2S), 26.8 (SCH2CH2CH2S), 38.3
(NCH2CH2CH2C), 39.6 (NCH2CH2CH2C), 56.6
2
(C2CS2), 115.3 (d, JCF = 21.4 Hz, C-3/C-5, CC6H4F),
3
130.2 (d, JCF = 8.4 Hz, C-2/C-6, CC6H4F), 137.6 (d,
1
4JCF = 3.3 Hz, C-1, CC6H4F), 161.1 (d, JCF = 244.9
Hz, C-4, CC6H4F). 19F NMR ([D6]DMSO): d ꢀ116.2.
Anal. Found: C, 50.8; H, 6.1; N, 4.6; S, 20.6. Calc. for
C13H19ClFNS2: C, 50.71; H, 6.22; N, 4.55; S, 20.83%.
d
1.56–1.74 (m, 2H, NCH2CH2CH2C), 1.78–1.97
(m, 2H, SCH2CH2CH2S), 1.97–2.10 (m, 2H,

46
T. Heinrich et al. / Journal of Organometallic Chemistry 690 (2005) 33–47
NCH2CH2CH2C), 2.56–2.65 (m, 4H, SCH2CH2CH2S),
3
3.53 (t, JHH = 7.0 Hz, 2H, NCH2CH2CH2C), 6.90–
CCDC-237708 (8), CCDC-237709 (9), CCDC-237710
(13 Æ HCl), CCDC-237711 (15 Æ HCl Æ 0.5EtOH), CCDC-
237712 (17 Æ H2O), and CCDC-237713 (18 Æ HCl).
Copies of the data may be obtained free of charge on
application to CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK (fax: +44 1223 336033; e-mail: deposit@
ccdc.cam.ac.uk). Supplementary data associated with
this article can be found, in the online version at
doi:10.1016/j.jorganchem.2004.08.023.
7.05 (m, 2H, H-3/H-5, CC6H4F), 7.62–7.73 (m,
2H, H-4/H-5, C(O)C6H4C(O)), 7.74–7.90 (m, 4H,
H-3/H-6, C(O)C6H4C(O), H-2/H-6, CC6H4F). 13C
NMR (75.5 MHz, CDCl3): d 23.2 (NCH2CH2CH2C),
25.0 (SCH2CH2CH2S), 27.5 (SCH2CH2CH2S), 37.6
(N- CH2CH2CH2C), 42.1 (NCH2CH2CH2C), 57.8
2
(C2CS2), 115.2 (d, JCF = 21.1 Hz, C-3/C-5, CC6H4F),
3
123.1 (C-3/C-6, C(O)C6H4C(O)), 130.6 (d, JCF = 8.0
Hz, C-2/C-6, CC6H4F), 132.0 (C-1/C-2, C(O)C6H4-
C(O)), 133.8 (C-4/C-5, C(O)C6H4C(O)), 137.0 (d,
4JCF = 2.9 Hz, C-1, CC6H4F), 161.6 (1JCF = 247.0
Hz, C-4, CC6H4F), 168.1 (CO). 19F NMR (CDCl3):
d ꢀ115.9. Anal. Found: C, 62.9; H, 5.0; N, 3.5; S,
15.8. Calc. for C21H20FNO2S2: C, 62.82; H, 5.02; N,
3.49; S, 15.97%.
References
[1] M. Gerlach, P. Jutzi, J.-P. Stasch, H. Przuntek, Z. Naturforsch. B
37 (1982) 657.
[2] J.-P. Stasch, H. Ruß, U. Schacht, M. Witteler, D. Neuser, M.
Gerlach, M. Leven, W. Kuhn, P. Jutzi, H. Przuntek, Arzneim.-
Forsch./Drug Res. 38 (II) (1988) 1075.
´ ´
[3] J. Barluenga, C. Jimenez, C. Najera, M. Yus, Synthesis (1982)
414.
4.2. Crystal structure analyses
[4] M. Kurono, Y. Kondo, Y. Baba, K. Sawai (Inventors). Sanwa
Kagaku Kenkyusho Co., Ltd., JP 4041494, February 12 1992;
Chem. Abstr. 117 (1992) 8191t.
Suitable single crystals of 5, 6 Æ HCl, 8, 9, 13 Æ HCl,
15 Æ HCl Æ 0.5EtOH, 17 Æ H2O, and 18 Æ HCl were ob-
tained by crystallization from 2-propanol (5, 9, 13 Æ
HCl, 18 Æ HCl), ethanol (6 Æ HCl, 15 Æ HCl Æ 0.5EtOH),
ethanol/ethyl acetate (2:1 (v/v)) (8), or ethanol/ethyl
acetate/water (2:1:0.1 (v/v/v)) (17 Æ H2O) at 20 ꢁC.
The crystals were mounted in inert oil (perfluoroalkyl
ether, ABCR) on a glass fiber and then transferred to
the cold nitrogen gas stream of the diffractometer
(Stoe IPDS; graphite-monochromated Mo Ka radia-
[5] B.M. Kim, J.H. Cho, Tetrahedron Lett. 40 (1999) 5333.
[6] R. Tacke, T. Heinrich, R. Bertermann, C. Burschka,
A. Hamacher, M. Kassack, Organometallics 23 (2004)
4468.
[7] Recent review dealing with silicon-based drugs: W. Bains, R.
Tacke, Curr. Opin. Drug Discovery Dev. 6 (2003) 526.
[8] Recent original publications dealing with silicon-based drugs:
(a) R. Tacke, M. Merget, R. Bertermann, M. Bernd, T. Beckers,
T. Reissmann, Organometallics 19 (2000) 3486;
(b) M. Merget, K. Gunther, M. Bernd, E. Gunther, R. Tacke,
¨ ¨
J. Organomet. Chem. 628 (2001) 183;
˚
tion (k = 0.71073 A)). The structures were solved by
direct methods [16,17]. All non-hydrogen atoms were
refined anisotropically [18]. Except for compound 5,
a riding model was employed in the refinement of
the CH hydrogen atoms. The NH and OH hydrogen
atoms were localized in difference Fourier syntheses
and refined freely, except for the OH hydrogen atom
of the solvent molecule in 15 Æ HCl Æ 0.5EtOH (riding
model).
(c) R. Tacke, T. Kornek, T. Heinrich, C. Burschka, M. Penka,
M. Pu¨lm, C. Keim, E. Mutschler, G. Lambrecht, J. Organomet.
Chem. 640 (2001) 140;
(d) J.O. Daiss, S. Duda-Johner, C. Burschka, U. Holzgrabe, K.
Mohr, R. Tacke, Organometallics 21 (2002) 803;
(e) R. Tacke, T. Heinrich, Silicon Chem. 1 (2002) 35;
(f) R. Tacke, V.I. Handmann, K. Kreutzmann, C. Keim, E.
Mutschler, G. Lambrecht, Organometallics 21 (2002) 3727;
(g) R. Tacke, V.I. Handmann, R. Bertermann, C. Burschka, M.
Penka, C. Seyfried, Organometallics 22 (2003) 916;
(h) S. Duda-Johner, J.O. Daiß, K. Mohr, R. Tacke, J. Organomet.
Chem. 686 (2003) 75;
(i) T. Heinrich, C. Burschka, J. Warneck, R. Tacke, Organome-
tallics 23 (2004) 361.
Acknowledgement
[9] S.D. Rosenberg, J.J. Walburn, T.D. Stankovich, A.E. Balint,
H.E. Ramsden, J. Org. Chem. 22 (1957) 1200.
This work was supported by the Fonds der Chemi-
schen Industrie.
[10] 2,2,2-Trichloroethyl chloroformate as N-demethylation agent:
T.A. Montzka, J.D. Matiskella, R.A. Partyka, Tetrahedron Lett.
15 (1974) 1325.
[11] For an alternative synthesis of 6 (Pd-catalyzed hydrogenation of
4; 48% yield), see: M. Gerlach, Ph.D. Thesis, University of
Wurzburg, 1982.
¨
Appendix A. Supplementary material
[12] Synthesis of 3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propylamine:
A.M. Ismaiel, J. De Los Angeles, M. Teitler, S. Ingher, R.A.
Glennon, J. Med. Chem. 36 (1993) 2519.
Crystallographic data (excluding structure factors)
for the crystal structures reported in this paper have
been deposited with the Cambridge Crystallo-
graphic Data Centre as supplementary publication
numbers CCDC-237706 (5), CCDC-237707 (6 Æ HCl),
[13] The use of the ‘‘dioxolane-protected’’ 4-chloro-(4-fluorophe-
nyl)butyrophenone proved to be necessary, since the unprotected
compound is deprotonated at C-2, leading to the formation of
6 Æ HCl and cyclopropyl(4-fluorophenyl)methanone (MS analysis).

T. Heinrich et al. / Journal of Organometallic Chemistry 690 (2005) 33–47
47
In this context, see also: W. Schliemann, A. Buge, L. Reppel,
¨
Pharmazie 35 (1980) 140.
Jeffrey, W. Saenger, Hydrogen Bonding in Biological Structures,
Springer, Berlin, 1991, pp. 15–24.
[14] 1-Chloroethyl chloroformate as N-dealkylation agent: R.A. Olof-
son, J.T. Martz, J.-P. Senet, M. Piteau, T. Malfroot, J. Org.
Chem. 49 (1984) 2081.
[16] G.M. Sheldrick, SHELXS-97, University of Go¨ttingen, Go¨ttingen,
Germany, 1997.
[17] G.M. Sheldrick, Acta Crystallogr., Sect.
467.
A
46 (1990)
[15] The hydrogen-bonding systems were analyzed by using the
program system PLATON. A.L. Spek, PLATON, University of
Utrecht, Utrecht, The Netherlands, 1998. In this context, see also:
[18] G.M. Sheldrick, SHELXL-97, University of Go¨ttingen, Go¨ttingen,
Germany, 1997.