Heterocyclization of N-(1-chloro-2,2,2-trifluoroethylidene)carbamates with β-enaminoesters - A novel synthetic strategy to functionalized trifluoromethylated pyrimidines

Article abstract of DOI:10.1016/j.tet.2012.07.099

A novel synthetic strategy to 4-trifluoromethyl substituted 2-oxo-1,2-dihydropyrimidine-5-carboxylates has been developed based on the cyclocondensation of β-enaminoesters with N-(1-chloro-2,2,2- trifluoroethylidene)carbamates.

Full text of DOI:10.1016/j.tet.2012.07.099

Supporting Information
Heterocyclization of N-(1-chloro-2,2,2-trifluoroethylidene)carbamates with β-
enaminoesters – a novel synthetic strategy to functionalized trifluoromethylated
pyrimidines
Volodymyr A. Sukach*, Viktor M. Tkachuk, Eduard B. Rusanov, Gerd-Volker Röschenthaler,
Mykhaylo V. Vovk
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Murmans’ka 5, Kyiv
02094, Ukraine
School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, 28759 Bremen,
Germany
*
Corresponding author. Fax: +380(44)5732643; e-mail: vsukach@bigmir.net
X-ray Structure determination for compound 5a.
Crystal data: C10
H
11
B
2
F
3
N
2
O
3
1
, M 285.83, monoclinic, space group P2 /c, а = 4.8955(6),
3
-3
b = 11.0400(15), c = 21.316(3) Å,  = 93.177(4)º, V = 1150.3(3)Å , Z = 4, d
c
= 1.56 g·cm ,  =
-
1
0
.148 mm , F(000) = 584, crystal size ca. 0.19 х 0.27 х 0.35 mm. All crystallographic
measurements were performed at room temperature on a Bruker Smart Apex II diffractometer
operating in the  and  scans mode. The intensity data were collected within the max  26.38
using Mo-K radiation ( = 0.71078 Å). The intensities of 5640 reflections were collected (2164

unique reflections, Rmerg = 0.0202).
The structure was solved by direct methods and refined by the full-matrix least-squares
technique in the anisotropic approximation for non-hydrogen atoms using the Bruker SHELXTL
1
program package . All hydrogen atoms were refined isotropically. In the refinement 2164
reflections (1539 reflections with I  (I)) were used. Convergence was obtained at R1 =
0
.0588 and wR2 = 0.1039, for all reflection and R1 = 0.0374 and wR2 = 0.0921, GOF = 1.007
for observed (207 parameters; observed/variable ratio 7.4; the largest and minimal peaks in the
3
2
2
final difference map 0.18 and –0.18 e/Å , weighting scheme is as follows:  = 1/[ (Fo ) +
2
2
2
0
.0509P +0.2021P], where Р = (Fo + 2Fc )/3). Full crystallographic details have been deposited

at Cambridge Crystallographic Data Centre (CCDC). Any request to the CCDC for these
materials should quote the full literature citation and reference number CCDC 878801.
X-ray Structure determination for compound 5l.
Crystal data: C35
H
30
F
6
N O
4 6
, M 716.63, monoclinic, space group P2
1
/c, а = 20.2101(4), b
3
-3
=
=
11.0539(2), c = 15.0422(3) Å,  = 100.384(1)º, V = 3305.40(11)Å , Z = 4, d = 1.44 g·cm , 
c
-1
0.121 mm , F(000) = 1480, crystal size ca. 0.19 х 0.27 х 0.35 mm. All crystallographic
measurements were performed at room temperature on a Bruker Smart Apex II diffractometer
operating in the  and  scans mode. The intensity data were collected within the range  
2
8.94 using Mo-K radiation ( = 0.71078 Å). The intensities of 35627 reflections were

collected (8636 unique reflections, Rmerg = 0.0509).
The structure was solved by direct methods and refined by the full-matrix least-squares
technique in the anisotropic approximation for non-hydrogen atoms using the Bruker SHELXTL
1
program package . The Et group one of the independent molecule is disordered over two position
with occupancy of 50%. The hydrogen atoms that supported N atoms where found in difference
Fourier maps and refined isotropically, rest ones is placed geometrically and refined as “riding”
model. In the refinement 8636 reflections (4990 reflections with I  (I)) were used.
Convergence was obtained at R1 = 0.1126 and wR2 = 0.1924, for all reflection and R1 = 0.0565
and wR2 = 0.1544, GOF = 1.061 for observed (467 parameters; observed/variable ratio 10.7; the
3
largest and minimal peaks in the final difference map 0.64 and –0.36 e/Å , weighting scheme is
2
2
2
2
2
as follows:  = 1/[ (Fo ) + (0.1P) ], where Р = (Fo + 2Fc )/3). Full crystallographic details
have been deposited at Cambridge Crystallographic Data Centre (CCDC). Any request to the
CCDC for these materials should quote the full literature citation and reference number CCDC
8
78802.
1
.Sheldrick, G. M. (2008). Acta Cryst. A 64, 112-122.
1
13
H and C–NMR spectra of compounds 5, 7, 9-12, 14

F
F
F
O
VS059
O
N
N
O
5a
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0

F
F
F
O
phvs059-C13
O
N
N
O
5a
170
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10

F
F
F
PHvs-072
O
O
N
N
O
5
b
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0

F
F
F
O
PHvs072-C13
O
N
N
O
5
b
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10

F
F
F
O
O
N
N
O
5c
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0

F
F
F
O
PHvs035-C13
O
N
N
O
5
c
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10

F
F
F
O
PHvs071
O
N
N
O
5
d
O
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0

F
F
F
O
PHvs064-C13
O
N
N
O
d
5
O
170
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10

F
F
F
O
phvs089v.fid
O
N
N
O
5
e
O
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0

F
F
F
O
PHvs089c-C13
O
N
N
O
5
e
O
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10

F
F
F
O
phvs085v - копия
O
N
N
O
5
f
O
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0

PHvs085c-C13
F
F
F
O
O
N
N
O
5
f
O
(
with toluene)
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10

PHvs154v.fid
F
F
F
O
O
N
N
O
H
5
g
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5

PHvs035-C13
F
F
F
O
O
N
N
O
H
5
g
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10

PHvs109v.fid
F
F
F
O
O
N
N
O
5
h
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5

F
F
F
O
O
N
N
O
5
h
170
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10

F
F
F
O
O
N
N
O
5
i
O
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0

F
F
F
O
O
N
N
O
5i
O
170
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10

F
F
F
O
O
N
N
O
5j
O
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0

F
F
F
O
O
N
N
O
5j
O
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10

F
F
F
O
O
N
N
O
Cl
5k
10.0
9.0
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0

F
F
F
O
O
N
N
O
Cl
5k
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10

F
F
F
O
O
N
N
O
H
5l
14.0
13.0
12.0
11.0
10.0
9.0
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0

F
F
F
O
O
N
N
O
H
5
l
170
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10

F
F
F
O
O
N
N
O
H
O
5m
14.0
13.0
12.0
11.0
10.0
9.0
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0

F
F
F
O
O
N
N
O
H
O
5
m
180
170
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10

F
F
F
O
O
N
N
O
5
n
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0

F
F
F
O
O
N
N
O
5
n
170
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10