Chlorotrimethylsilane-mediated synthesis of 2-aryl-1-chloro-1- heteroarylalkenes

Article abstract of DOI:10.1055/s-2007-990791

The condensation of (chloromethyl)heterarenes with aromatic aldehydes was investigated, resulting in a simple and flexible general procedure for the synthesis of 2-aryl-1-chloro-1-heteroarylalkenes. The best reaction conditions were found to be heating in N,N-dimethylformamide in the presence of chlorotrimethylsilane as a promoter and water-scavenger. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-990791

PAPER
3163
Chlorotrimethylsilane-Mediated Synthesis of 2-Aryl-1-chloro-1-heteroaryl-
alkenes
C
hlorotrimeth
e
r
diated
S
g
ynthesis of
2
e
-Aryl-1-c
h
y
loro-1-heteroarylalk
V
ene
s
. Ryabukhin,a,b Andrey S. Plaskon,a,b Dmitriy M. Volochnyuk,*a,c Andrey A. Tolmachevb
a
b
c
Enamine Ltd., 23 Alexandra Matrosova st., 01103 Kiev, Ukraine
National Taras Shevchenko University, 62 Volodymyrska st., 01033 Kiev, Ukraine
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Murmanska 5, 02094 Kiev, Ukraine
Fax +380(44)5373253; E-mail: D.Volochnyuk@enamine.net
Received 3 June 2007; revised 21 June 2007
In the present work, the results of studying the Knoevena-
gel condensation using chloromethyl-substituted hetero-
cycles and the corresponding alcohols and their tosylates
are reported.
Abstract: The condensation of (chloromethyl)heterarenes with
aromatic aldehydes was investigated, resulting in a simple and
flexible general procedure for the synthesis of 2-aryl-1-chloro-1-
heteroarylalkenes. The best reaction conditions were found to be
heating in N,N-dimethylformamide in the presence of chlorotri-
methylsilane as a promoter and water-scavenger.
We have previously shown17 that (benzothiazolyl)metha-
nol 1 reacts with benzaldehyde in the presence of
chlorotrimethylsilane18,19 in a pressure tube affording
(benzothiazolyl)ethanone 3 (Scheme 2). An attempt to ap-
ply this approach to (benzimidazolyl)methanol 2 resulted
in the formation of (1-chlorovinyl)benzimidazole 5 as the
major product instead of (benzimidazolyl)ethanone 4 un-
der the same conditions. We hypothesized that formation
of compound 5 could be rationalized by substitution of the
silylated hydroxy group with chlorine in intermediates 6.
For indirect confirmation of our hypothesis we decided to
perform the reaction of (chloromethyl)benzimidazole 7
with benzaldehyde under similar conditions. The sole
product 5 was formed in 84% preparative yield.
Key words: (chloromethyl)heterocycles, aromatic aldehydes,
Knoevenagel condensation, 2-aryl-1-halo-1-heteroarylalkene, chlo-
rotrimethylsilane
1-Halo-1-heteroarylalkenes I have attracted much atten-
tion due to their diverse biological activity.1–4 The biolog-
ical activity of this type of compound is generally defined
by the nature of the heterocycle, however, the presence of
the halide influences the activity parameters and is neces-
sary for QSAR building. These compounds also have in-
terest as dyes.5
There are some approaches to these substances reported in
the literature (Scheme 1). These are: introduction of the
halide atom into the heteroaryl-substituted alkenes II us-
ing halogenating agents (route 1);1a,d,6 elimination of
HHal from 1,2-dihalo-1-heteroarylalkanes III (route 2);7
hydrohalogenation of alkynes IV (route 3);8 elimination
of HHal from 1,1-dihalo-1-heteroarylalkanes V (route 4);9
from 1,1,1-trichloromethyl derivatives VI (route 5);10 het-
eroarylation of tributylhalostannanes VII (route 6);2a,11
halogenation of tributylstannanes VIII (route 7);4,12 and
reaction of 1,1-dihaloalkenes IX with heteroarylzinc com-
pounds X (route 8).13 There are also some useful ap-
proaches to 1-halo-1-heteroarylalkenes that use
cyclization reactions at the last step of the synthe-
sis.1b,c,2b,14 However, the most facile and promising meth-
od for the preparation of these compounds is the
condensation of (halomethyl)heterarenes XII with alde-
hydes (route 9).1e,3a,15,16 The condensation should be per-
formed under acidic conditions because under basic
conditions the intermediate hydrins XI undergo cycliza-
tion into oxiranes via Darzens reaction.15b However, this
approach has only been applied to a few heterocycles and
has not been widely utilized.
The result obtained with (chloromethyl)benzimidazole 7
was extended to a set of chloromethyl derivatives of other
heterocycles 8–22. In all cases shown in Table 1, the reac-
tion proceeds in high preparative yields forming the cor-
responding chloroalkene derivative 24–38 as the sole
reaction product. It should be noted that these compounds
have the Z configuration as was confirmed by NOE exper-
iments on three compounds of this series (Figure 1).
Among the chloromethyl derivatives of p-electron-with-
drawing heterocycles that were unsuccessful in this reac-
tion was 2-(chloromethyl)-1-methyl-1H-imidazole. In
weak NOE
Cl
H
Cl
N
N
Cl
H
H
H
H
H
H
strong NOE
NOESY
weak NOE
strong NOE
strong NOE
26
25
CH3
N
S
HN
O
H
H
Cl
SYNTHESIS 2007, No. 20, pp 3163–3170
Advanced online publication: 21.09.2007
x
x.
x
x
.
2
0
0
7
31
DOI: 10.1055/s-2007-990791; Art ID: P07207SS
© Georg Thieme Verlag Stuttgart · New York
Figure 1

3164
S. V. Ryabukhin et al.
PAPER
Hal
Hal
H
R
Het
R
Het
Het
Hal
Hal
R
IV
Cl
Cl
V
Het
Cl
III
II
VI
route 4
route 3
R
route 2
route 5
Hal
route 1
Het
route 6
Bu3Sn
VII
R
R
Het
Hal
I
route 10
route 7
route 8
route 9
OH
Het
Bu3Sn
Hal
+
R
Het
O
R
Het
Hal
Hal
XIII
XII
VIII
Hal
R
R
this work
IX
+
XI
HetZnBr
Hal
X
Het
XII
Scheme 1
:Cl–
OTMS
R
nucleophilic substitution/
elimination
N
N
OTMS
OTMS
6
direct elimination
of (TMS)2O
O
N
i
Cl
N
OH
N
X
+
N
H
N
H
R
X = NH
R
5
4
1: X = S
2: X = NH
1:4
Ref. 17
X = S
i
i
O
N
S
Cl
N
R = 4-ClC6H4
N
H
3
7
R
Scheme 2 Reagents and conditions: (i): PhCHO, DMF, TMSCl, 100 °C, 6 h, pressure tube.
this case, a complicated mixture of products with no trace the initial silylation on heterocyclic nitrogen of the start-
of the target chlorovinyl derivative was formed. This was ing (halomethyl)hetarene 8–22 followed by addition of al-
accounted for by the insufficiently low acceptor proper- dehyde to 41 resulting in the intermediate 40 (Scheme 3)
ties of the imidazole ring in comparison to other heterocy-
cles in Table 1.
Unfortunately, we did not succeed in extending this ap-
proach to other types of CH-acidic chloromethyl deriva-
We propose that the process can run via two pathways. tives. Under similar conditions 4-nitrobenzoyl chloride
The first implies that initially formed O-silyl derivative 39 and monochloroacetic acid amides do not enter into the
undergoes silylation at the heterocyclic nitrogen resulting reaction with aldehydes, while chloroacetic ester and
in the formation of disilyl derivative 40. Extrusion of chloroacetophenones give complicated product mixtures,
hexamethyldisilazane gives the target 2-aryl-1-chloro-1- with no target products being detected.
heteroarylalkenes 24–38. The second pathway includes
Synthesis 2007, No. 20, 3163–3170 © Thieme Stuttgart · New York

PAPER
Chlorotrimethylsilane-Mediated Synthesis of 2-Aryl-1-chloro-1-heteroarylalkenes
3165
Table 1 Preparation of 2-Aryl-1-chloro-1-heteroarylalkenesa
N
N
X
TMSCl
DMF
Y
O
+
X
Cl
Cl
Y
8–22
23a–e
24–38
Y = a: H, b: OMe, c: Cl, d: NO2, e: COOMe
Starting material
23
Product
Yieldb (%)
82
Cl
N
N
23b
O
OMe
O
Cl
8
9
24
Cl
23c
23a
23b
78
75
74
Cl
Cl
N
Cl
N
25
Cl
N
N
10
26
Cl
N
N
O
O
OMe
Cl
Ph
Ph
11
27
Cl
N
O
N
N
N
NO2
23d
83
O
F
Cl
F
12
28
Ph
Cl
N
O
Ph
N
O
23e
23b
85
87
N
N
COOMe
Cl
13
29
N
Cl
N
N
N
BnNH
BnNH
S
Cl
S
OMe
O
O
N
14
30
O
O
N
HN
HN
23a
23b
23e
77
96
86
Cl
Cl
MeS
MeS
15
31
O
O
NH
N
Cl
NH
OMe
Cl
Cl
N
O
16
17
32
33
O
O
N
Cl
O
COOMe
N
Synthesis 2007, No. 20, 3163–3170 © Thieme Stuttgart · New York

3166
S. V. Ryabukhin et al.
PAPER
Table 1 Preparation of 2-Aryl-1-chloro-1-heteroarylalkenesa (continued)
N
N
X
TMSCl
DMF
Y
O
+
X
Cl
Cl
Y
8–22
23a–e
24–38
Y = a: H, b: OMe, c: Cl, d: NO2, e: COOMe
Starting material
23
Product
Yieldb (%)
O
O
NH
Cl
NH
23b
91
N
OMe
Cl
S
N
S
18
34
O
O
NH
N
Cl
S
NH
23b
23e
95
78
S
OMe
Cl
N
19
35
H2N
NH2
EtOOC
N
Cl
EtOOC
N
Me
N
COOMe
Cl
O
N
O
Me
20
36
O
N
O
COOMe
Br
N
23e
23c
75
89
Br
N
Cl
Cl
N
21
37
Cl
Cl
N
Cl
N
22
38
a Satisfactory microanalysis obtained: C 0.33; H 0.45; N 0.25.
b Yields refer to pure isolated products.
A further disadvantage of this approach is that some
(chloromethyl)hetarenes are difficult to access or have
low stability. For example, the 2-(chloromethyl)benzo-
thiazole possesses low stability under the reaction condi-
tions. In this case, to obtain the corresponding chlorovinyl
derivative we decided to use an approach similar to that
used for the preparation of vinyl chloride 5 from (benzim-
idazolyl)methanol 2 (Scheme 2). In order to increase the
nucleofugicity of the leaving group in intermediates of
type 6, the hydroxylic group of the starting (benzothiaz-
olyl)methanol 1 was tosylated. Using the tosylate 42 gave
chloro derivative 43 in 93% preparative yield. We assume
that the reaction proceeds via an intermediate 44, the nu-
cleophilic substitution of the tosylate group leads to inter-
mediate 45. The confirmation of the generality of this
reaction is the transformation of tosylate 46, which is a
quinoline derivative, into chlorovinyl derivative 38 in
95% yield (Scheme 4). Compound 38 has also had its Z
configuration confirmed by NOE experiments.
N
A
Cl
TMSCl
Ar
ArCHO
TMSCl
TMS
O
TMSO
Ar
TMS
39
– TMS2O
8–22
24–38
N
Cl
SiMe3
A
TMSCl
N
40
ArCHO
TMSCl
A
Cl
41
Scheme 3
finity of fluorine to silicon. We carried out the reaction of
(fluoromethyl)benzothiazole 47 with aldehyde 23b. How-
ever, substitution of fluorine does not occur and the fluo-
rovinyl derivative 48 was isolated in 85% yield
(Scheme 5).
We attempted to extend this approach and introduce,
through the tosyl derivative, bromine and iodine to the
We also tried to use fluorine as a nucleofuge for which a
trimethylsilyl group is a good acceptor due to the high af-
Synthesis 2007, No. 20, 3163–3170 © Thieme Stuttgart · New York

PAPER
Chlorotrimethylsilane-Mediated Synthesis of 2-Aryl-1-chloro-1-heteroarylalkenes
3167
double bond using bromotrimethylsilane and iodotrimeth- a promoter and water-scavenger. The methodology is ap-
ylsilane (generated in situ from TMSCl and NaI in plicable to a wide variety of (chloromethyl)heterarenes
DMF),20 respectively, instead of chlorotrimethylsilane. and delivers the target products in good yields. The chem-
However, in the case of bromotrimethylsilane the reaction ical procedure is very simple and could be easily adapted
proceeds unselectively giving a mixture of products. The to semi-automated solution-phase parallel synthesis of 2-
target bromovinyl 49 was identified by HPLC MS spectra aryl-1-chloro-1-heteroarylalkene libraries.
of the product mixture; however it could not be isolated.
In the case of iodotrimethylsilane, the reduction to alkene
50 occurs in 72% yield (Scheme 6).
All commercially available starting materials (Aldrich, Fluka,
Enamine Ltd) were used without additional purification. All sol-
vents were purified by standard methods. All procedures were car-
ried out under open atmosphere with no precautions taken to
exclude ambient moisture. Melting points were measured with a
Buchi melting points apparatus and are uncorrected. 1H NMR (400
MHz and 500 MHz) were recorded on a Varian Mercury-400 spec-
trometer and Bruker Avance DRX 500 spectrometer with TMS as
an internal standard. 13C NMR (125 MHz) were recorded on a Bruk-
er Avance DRX 500 spectrometer with TMS as an internal standard.
19F NMR (470 MHz) were recorded on a Bruker Avance DRX 500
spectrometer with CFCl3 as an internal standard. NOE and NOESY
experiments were recorded on a Bruker Avance DRX 500 spec-
trometer. LC/MS spectra were recorded using chromatography/
mass spectrometric system that consists of high-performance liquid
chromatograph Agilent 1100 Series equipped with diode-matrix
and mass-selective detector Agilent LC\MSD SL. The parameters
of chromatography-mass analysis: column: Zorbax SB-C18, 1.8
mm, 4.6 mm × 15 mm; eluent, A: MeCN–H2O (95:5) + 0.1% TFA;
B: H2O + 0.1% TFA; flow rate: 3 mL/sec; volume of injected sam-
ple: 1 mL; UV detectors: 215, 254, and 265 nm; ionization method:
CI under atmospheric pressure (APCI); ionization mode, simulta-
neous scanning of positive and negative ions in the mass range of
80–1000. According to HPLC-MS data all the synthesized com-
pounds have purity >98%. Branson 2510E-MT ultrasonic bath was
used.
Cl
N
S
OTs
N
i
93 %
OMe
S
42
43
:Cl–
Cl
N
OTs
N
– OTs–
Ar
OTMS
S
S
Ar
OTMS
44
45
strong NOE
Cl
H
i
OTs
N
Cl
95%
N
H
46
38
H
H
weak
NOE
strong
NOE
2-Aryl-1-halo-1-heteroarylalkenes 5, 24–38, and 48, and 1-Aryl-
2-heteroarylalkene 50; General Procedure
Scheme 4 Reagents and conditions: (i) 23b (for 43) or 23c (for 38),
DMF, TMSCl, 100 °C, 6 h, pressure tube.
(Chloromethyl)heterocycle 7, 8–22 or (fluoromethyl)benzothiazole
47 (2 mmol) and an appropriate aromatic aldehyde 23a–e (2 mmol)
were placed in a 15-mL pressure tube and dissolved in DMF (2–3
mL). TMSCl (6 mmol) (TMSI in the case of 50) was added drop-
wise to the soln. The tube was thoroughly sealed and heated on a
water bath for 6–15 h. After cooling the flask was opened (Caution!
Excessive pressure.) and the mixture was poured into H2O (15 mL)
and allowed to stand at 20 °C in an ultrasonic bath for 1 h. The pre-
cipitate formed was filtered and washed with small amount of i-
PrOH. Recrystallization from an appropriate solvent yielded target
compounds 5, 24–38, 48, and 50 (see Table 1 and Schemes 5
and 6).
F
N
S
F
N
S
i
OMe
85%
47
48
Scheme 5 Reagents and conditions: (i) 23b, DMF, TMSCl, 100 °C,
6 h, pressure tube.
Br
N
S
i
one of the products
observed in reaction
mixture, separation
failed
2-[(Z)-1-Chloro-2-(4-chlorophenyl)vinyl]-1H-benzimidazole
Hydrochloride (5)
Yield: 84%; mp 242–243 °C (MeCN).
1H NMR (400 MHz, DMSO-d6): d = 7.36 (m, 2 H, 5,6-HBIm), 7.60
(d, 3JH,H = 8.5 Hz, 2 H, 3,5-HAr), 7.67 (m, 2 H, 4,7-HBIm), 7.94 (d,
3JH,H = 8.5 Hz, 2 H, 2,6-HAr), 8.18 (s, 1 H, CH).
13C NMR (125 MHz, DMSO-d6): d = 115.0, 117.0, 125.7, 129.5,
132.1, 132.4, 133.5, 134.7, 135.5, 147. 7.
MS (APSI): m/z = 289 [M + 1]+.
49
50
42
N
S
ii
Scheme 6 Reagents and conditions: (i) 23a, DMF, TMSBr, 100 °C,
6 h, pressure tube; (ii) 23a, DMF, TMSI, 100 °C, 6 h, pressure tube.
2-[(Z)-1-Chloro-2-(4-methoxyphenyl)vinyl]benzoxazole (24)
Yield: 82%; mp 123–124 °C (EtOH).
In summary, we have developed efficient methodology
for the preparation of 2-aryl-1-chloro-1-heteroarylalkenes
from (chloromethyl)heterarenes or (tosyloxymeth-
yl)hetarenes and aldehydes using chlorotrimethylsilane as
1H NMR (400 MHz, DMSO-d6): d = 3.83 (s, 3 H, OCH3), 7.08 (d,
3JH,H = 8.9 Hz, 2 H, 3,5-HAr), 7.44 (m, 2 H, 5,6-HBOx), 7.76 (d,
Synthesis 2007, No. 20, 3163–3170 © Thieme Stuttgart · New York

3168
S. V. Ryabukhin et al.
PAPER
N-Benzyl-5-[(Z)-1-chloro-2-(4-methoxyphenyl)vinyl]-1,3,4-
3JH,H = 7.6 Hz, 1 H, 4-HBOx), 7.80 (d, 3JH,H = 7.6 Hz, 1 H, 7-HBOx),
8.01 (d, 3JH,H = 8.9 Hz, 2 H, 2,6-HAr), 8.07 (s, 1 H, CH).
thiadiazole-2-carboxamide (30)
Yield: 87%; mp 165–166 °C (MeCN).
13C NMR (125 MHz, DMSO-d6): d = 55.9, 111.3, 114.8, 114.9,
120.5, 125.6, 125.9, 126.5, 132.9, 133.6, 141.8, 150.9, 160.8, 161.2.
1H NMR (500 MHz, DMSO-d6): d = 3.82 (s, 3 H, OCH3), 4.47 (d,
3
3JH,H = 5.4 Hz, 2 H, CH2), 7.07 (d, JH,H = 8.2 Hz, 2 H, 3,5-HAr),
MS (APSI): m/z = 286 [M + 1]+.
7.25 (m, 1 H, 4-HPh), 7.33 (s, 4 H, 2,3,5,6-HPh), 7.95 (d, 3JH,H = 8.2
Hz, 2 H, 2,6-HAr), 8.06 (s, 1 H, CH), 9.85 (br s, 1 H, NH).
2-[(Z)-1-Chloro-2-(4-chlorophenyl)vinyl]pyridine Hydro-
chloride (25)
Yield: 78%; mp 82–83 °C (EtOH).
1H NMR (400 MHz, DMSO-d6): d = 7.44 (m, 1 H, 5-HPy), 7.53 (d,
3JH,H = 8.2 Hz, 2 H, 3,5-HAr), 7.89 (m, 2 H, 2,6-HAr), 7.94 (m, 2 H,
3,4-HPy), 8.07 (s, 1 H, CH), 8.66 (m, 1 H, 6-HPy).
13C NMR (125 MHz, DMSO-d6): d = 43.2, 55.9, 114.8, 116.8,
125.7, 127.5, 128.0, 128.8, 132.88, 132.92, 139.1, 157.9, 161.3,
165.8, 172.3.
MS (APSI): m/z = 386 [M + 1]+.
6-[(Z)-1-Chloro-2-phenylvinyl]-2-(methylsulfanyl)pyrimidin-
4(3H)-one (31)
Yield: 77%; mp 244–245 °C (EtOH).
13C NMR (125 MHz, DMSO-d6): d = 121.2, 124.3, 127.0, 129.0,
130.7, 132.0, 133.6, 133.7, 138.1, 149.7, 153.7.
MS (APSI): m/z = 250 [M + 1]+.
1H NMR (500 MHz, DMSO-d6): d = 2.60 (s, 3 H, SCH3), 7.42 (t,
3
3JH,H = 7.6 Hz, 1 H, 4-HPh), 7.47 (t, JH,H = 7.6 Hz, 2 H, 3,5-HPh),
4-[(Z)-1-Chloro-2-phenylvinyl]pyridine Hydrochloride (26)
Yield: 75%; mp 214–215 °C (EtOH).
1H NMR (500 MHz, DMSO-d6): d = 7.46 (d, 3JH,H = 7.8 Hz, 1 H, 4-
HPh), 7.51 (t, 3JH,H = 7.8 Hz, 2 H, 3,5-HPh), 7.92 (d, 3JH,H = 7.8 Hz, 2
H, 2,6-HPh), 8.09 (s, 1 H, CH), 8.27 (d, 3JH,H = 5.4 Hz, 2 H, 3,5-HPy),
8.90 (d, 3JH,H = 5.4 Hz, 2 H, 2,6-HPy).
7.84 (d, 3JH,H = 7.6 Hz, 2 H, 2,6-HPh), 8.22 (s, 1 H, CH), 12.88 (br s,
1 H, NH).
13C NMR (125 MHz, DMSO-d6): d = 13.6, 107.0, 127.7, 129.1,
130.0, 130.7, 131.6, 134.1, 157.3, 163.2, 165.7.
MS (APSI): m/z = 279 [M + 1]+.
13C NMR (125 MHz, DMSO-d6): d = 122.5, 126.8, 129.1, 130.3,
2-[(Z)-1-Chloro-2-(4-methoxyphenyl)vinyl]quinazolin-4(3H)-
one (32)
Yield: 96%; mp 213–214 °C (DMF–MeOH).
130.6, 133.4, 134.2, 145.6, 150.3.
MS (APSI): m/z = 216 [M + 1]+.
1H NMR (400 MHz, DMSO-d6): d = 3.86 (s, 3 H, OCH3), 6.98 (d,
3JH,H = 8.9 Hz, 2 H, 3,5-HAr), 7.46 (t, 3JH,H = 8.0 Hz, 1 H, 7-HQnz),
7.70 (t, 3JH,H = 8.0 Hz, 1 H, 6-HQnz), 7.77 (d, 3JH,H = 8.0 Hz, 1 H, 8-
2-[(Z)-1-Chloro-2-(4-methoxyphenyl)vinyl]-5-phenyloxazole
(27)
Yield: 74%; mp 95–96 °C (EtOH).
H
Qnz), 7.89 (d, 3JH,H = 8.9 Hz, 2 H, 2,6-HAr), 7.91 (s, 1 H, CH), 8.14
1H NMR (400 MHz, DMSO-d6): d = 3.86 (s, 3 H, OCH3), 6.99 (d,
(d, 3JH,H = 8.0 Hz, 1 H, 5-HQnz), 12.08 (br s, 1 H, NH).
3
3JH,H = 8.9 Hz, 2 H, 3,5-HAr), 7.35 (t, JH,H = 7.2 Hz, 1 H, 4-HPh),
13C NMR (125 MHz, DMSO-d6): d = 55.8, 114.7, 121.5, 126.3,
126.40, 126.42, 127.6, 128.0, 132.6, 133.2, 135.2, 148.5, 150.8,
160.8, 162.2.
7.46 (t, 3JH,H = 7.2 Hz, 2 H, 3,5-HPh), 7.64 (s, 1 H, 4-HOx), 7.76 (d,
3JH,H = 7.2 Hz, 2 H, 2,6-HPh), 7.88 (d, 3JH,H = 8.9 Hz, 2 H, 2,6-HAr),
7.91 (s, 1 H, CH).
MS (APSI): m/z = 313 [M + 1]+.
13C NMR (125 MHz, DMSO-d6): d = 55.9, 114.7, 115.1, 124.7,
125.0, 126.3, 127.5, 129.4, 129.6, 130.5, 132.4, 151.9, 158.6, 160.8.
MS (APSI): m/z = 312 [M + 1]+.
Methyl 4-[(Z)-2-Chloro-2-(4-oxo-4H-3,1-benzoxazin-2-yl)vi-
nyl]benzoate (33)
Yield: 86%; mp 264–265 °C (DMF–MeOH).
2-[(Z)-1-Chloro-2-(4-nitrophenyl)vinyl]-5-(4-fluorophenyl)-
1,3,4-oxadiazole (28)
Yield: 83%; mp 181–182 °C (EtOH).
1H NMR (400 MHz, DMSO-d6): d = 7.37 (d, 3JH,H = 3JH,F = 8.5 Hz,
2 H, 3,5-HAr), 8.16–8.26 (m, 5 H, 2,6-HAr, 2,6-HAr¢,CH), 8.33 (d,
3JH,H = 8.8 Hz, 2 H, 3,5-HAr¢).
13C NMR (125 MHz, DMSO-d6): d = 117.3 (2JC,F = 22.1 Hz),
117.6, 120.0 (4JC,F = 3.1 Hz), 124.3, 130.2 (3JC,F = 9.4 Hz), 131.7,
132.0, 139.5, 148.0, 162.6, 164.5, 165.0 (1JC,F = 250.8 Hz).
1H NMR (400 MHz, DMSO-d6): d = 3.87 (s, 3 H, OCH3), 7.24 (t,
3
3JH,H = 8.5 Hz, 1 H, 6-HHet), 7.67 (t, JH,H = 8.5 Hz, 1 H, 7-HHet),
7.98 (d, 3JH,H = 8.7 Hz, 2 H, 2,6-HAr), 8.04 (d, 3JH,H = 8.7 Hz, 2 H,
3,5-HAr), 8.05 (m, 1 H, 8-HHet), 8.10 (s, 1 H, CH), 8.66 (d,
3JH,H = 8.5 Hz, 1 H, 4-HHet).
13C NMR (125 MHz, DMSO-d6): d = 52.8, 117.4, 120.4, 124.2,
126.1, 129.8, 130.8, 130.9, 131.8, 133.8, 134.8, 137.7, 140.6, 160.3,
166.1, 170.1.
MS (APSI): m/z = 342 [M + 1]+.
19F NMR (470 MHz, DMSO-d6): d = –106.9.
MS (APSI): m/z = 346 [M + 1]+.
2-[(Z)-1-Chloro-2-(4-methoxyphenyl)vinyl]-5,6-dimethyl-
thieno[2,3-d]pyrimidin-4(3H)-one (34)
Yield: 91%; mp 257–258 °C (DMF–MeOH).
Methyl 4-[(Z)-2-Chloro-2-(3-phenyl-1,2,4-oxadiazol-5-yl)vi-
nyl]benzoate (29)
Yield: 85%; mp 146–147 °C (EtOH).
1H NMR (400 MHz, DMSO-d6): d = 3.91 (s, 3 H, OCH3), 7.50–7.59
(m, 3 H, 2,6-HAr, 4-HPh), 8.04–8.12 (m, 6 H, 3,5-HAr, 2,3,5,6-HPh),
8.24 (s, 1 H, CH).
1H NMR (400 MHz, DMSO-d6): d = 2.42 (s, 3 H, CH3), 2.45 (s, 3
H, CH3), 3.86 (s, 3 H, OCH3), 6.96 (d, 3JH,H = 8.9 Hz, 2 H, 3,5-HAr),
7.86 (d, 3JH,H = 8.9 Hz, 2 H, 2,6-HAr), 11.98 (br s, 1 H, NH).
13C NMR (125 MHz, DMSO-d6): d = 13.2, 13.3, 55.8, 114.6, 120.7,
122.4, 126.3, 129.4, 131.1, 132.5, 133.0, 150.3, 159.0, 160.8, 161.9.
13C NMR (125 MHz, DMSO-d6): d = 52.9, 116.7, 126.2, 127.7,
128.8, 129.9, 131.3, 132.4, 133.8, 136.0, 137.2, 166.1, 169.0, 173.7.
MS (APSI): m/z = 347 [M + 1]+.
MS (APSI): m/z = 341 [M + 1]+.
2-[(Z)-1-Chloro-2-(4-methoxyphenyl)vinyl]thieno[3,2-d]pyrim-
idin-4(3H)-one (35)
Yield: 95%; mp 260–261 °C (DMF–MeOH).
Synthesis 2007, No. 20, 3163–3170 © Thieme Stuttgart · New York

PAPER
Chlorotrimethylsilane-Mediated Synthesis of 2-Aryl-1-chloro-1-heteroarylalkenes
3169
1H NMR (400 MHz, DMSO-d6): d = 3.85 (s, 3 H, OCH3), 6.96 (d,
3JH,H = 8.8 Hz, 2 H, 3,5-HAr), 7.36 (d, 3JH,H = 5.0 Hz, 1 H, 4-HTh),
7.84–7.91 (m, 3 H, 2,6-HAr, CH), 7.99 (d, JH,H = 5.0 Hz, 1 H, 4-
2-[(E)-2-Phenylvinyl]benzothiazole (50)
Mp 104–105 °C (EtOH) (Lit. 104,21a 112,21b 109–110,21c 98–
10021d).
3
HTh), 12.35 (br s, 1 H, NH).
13C NMR (125 MHz, DMSO-d6): d = 55.8, 114.7, 121.2, 122.2,
125.8, 126.3, 132.5, 133.2, 136.0, 152.8, 157.7, 158.5, 160.9.
1H NMR data of this compound were in agreement with previously
reported data.21
APSI-MS: [M + 1]+ = 238.
MS (APSI): m/z = 319 [M + 1]+.
2-Aryl-1-chloro-1-heteroarylalkenes 38 and 43; General Proce-
dure
Ethyl 4-Amino-2-{(Z)-1-chloro-2-[4-(methoxycarbonyl)phe-
nyl]vinyl}-6-methylfuro[2,3-d]pyrimidine-5-carboxylate (36)
Yield: 78%; mp 189–190 °C (MeCN).
2-(Tosyloxymethyl)hetarenes 42 or 46 (2 mmol) and an appropriate
aromatic aldehyde 23b,c (2 mmol) were placed in a 15-mL pressure
tube and dissolved in DMF (2–3 mL). TMSCl (6 mmol) was added
dropwise to the soln. The tube was thoroughly sealed and heated on
a water bath for 8 h. After cooling the flask was opened (Caution!
Excessive pressure.) and the mixture was poured into H2O (15 mL)
and allowed to stand at 20 °C in an ultrasonic bath for 1 h. The pre-
cipitate formed was filtered and washed with small amount of i-
PrOH. Recrystallization from an appropriate solvent yielded target
compounds 38 (95% yield) and 43 (93% yield).
3
1H NMR (400 MHz, DMSO-d6): d = 1.34 (t, JH,H = 7.2 Hz, 3 H,
OCH2CH3), 2.67 (s, 3 H, CH3), 3.86 (s, 3 H, OCH3), 4.33 (q,
3
3JH,H = 7.2 Hz, 2 H, OCH2CH3), 7.95 (d, JH,H = 8.8 Hz, 2 H, 2,6-
HAr), 7.97–8.05 (m, 4 H, 3,5-HAr, NH2), 8.20 (s, 1 H, CH).
13C NMR (125 MHz, DMSO-d6): d = 14.4, 15.1, 52.7, 62.1, 98.3,
108.5, 129.7, 129.8, 130.5, 132.1, 139.0, 157.5, 158.2, 160.5, 162.8,
164.6, 165.8, 166.2.
MS (APSI): m/z = 416 [M + 1]+.
2-[(Z)-1-Chloro-2-(4-methoxyphenyl)vinyl]benzothiazole (43)
Yield: 93%; mp 121–122 °C (MeCN).
Methyl 4-[(Z)-2-(7-Bromo-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-
yl)-2-chlorovinyl]benzoate (37)
Yield: 75%; mp 222–223 °C (DMF–MeOH).
1H NMR (400 MHz, DMSO-d6): d = 3.87 (s, 3 H, OCH3), 6.98 (d,
3JH,H = 8.9 Hz, 2 H, 3,5-HAr), 7.39 (t, 3JH,H = 7.9 Hz, 1 H, 5-HBTz),
3
3
1H NMR (400 MHz, DMSO-d6): d = 3.89 (s, 3 H, OCH3), 6.91 (s, 1
7.50 (t, JH,H = 7.9 Hz, 1 H, 6-HBTz), 7.89 (d, JH,H = 8.9 Hz, 2 H,
2,6-HAr), 7.96 (d, 3JH,H = 7.9 Hz, 2 H, 4,7-HBTz), 8.05 (s, 1 H, CH).
H, 3-HHet), 7.67 (d, 3JH,H = 9.5 Hz, 1 H, 9-HHet), 7.98 (d, 3JH,H = 8.4
3
13C NMR (125 MHz, DMSO-d6): d = 55.9, 114.8, 121.2, 122.8,
123.4, 126.0, 126.1, 127.4, 130.3, 132.7, 135.4, 153.8, 161.0, 167.2.
MS (APSI): m/z = 302 [M + 1]+.
Hz, 2 H, 2,6-HAr), 8.04 (d, JH,H = 8.4 Hz, 2 H, 3,5-HAr), 8.10 (dd,
3JH,H = 9.5 Hz, 4JH,H = 2.3 Hz, 1 H, 8-HHet), 8.34 (s, 1 H, CH), 8.96
(d, 4JH,H = 2.3 Hz, 1 H, 6-HHet).
13C NMR (125 MHz, DMSO-d6): d = 52.7, 100.6, 126.5, 127.26,
127.32, 128.1, 128.9, 129.6, 129.7, 129.9, 130.7, 140.2, 158.1,
159.6, 161.8, 173.1.
Acknowledgment
MS (APSI): m/z = 419 [M + 1]+.
The authors acknowledge V. V. Polovinko (Enamine Ltd.) for spec-
tral measurements and Dr. A. N. Kostyuk for helpful discussions
and suggestions upon preparation of the manuscript.
2-[(Z)-1-Chloro-2-(4-chlorophenyl)vinyl]quinoline Hydro-
chloride (38)
Yield: 89%; mp 95–96 °C (MeCN).
3
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Synthesis 2007, No. 20, 3163–3170 © Thieme Stuttgart · New York

3170
S. V. Ryabukhin et al.
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Synthesis 2007, No. 20, 3163–3170 © Thieme Stuttgart · New York