Heterocyclization of 2-chloro-1-cyano-1-diethoxyphosphoryl-2- trifluoromethylethylene and 2-chloro-2-chlorodifluoromethyl-1-cyano-1- diethoxyphosphorylethylene

Article abstract of DOI:10.1007/s11172-005-0073-2

The reactions of 2-chloro-1-cyano-1-diethoxyphosphoryl-2- trifluoromethylethylene (2a) and 2-chloro-2-chlorodifluoromethyl-1-cyano-1- diethoxyphosphorylethylene (2b) with arylamines, arylhydrazines, amidines, 2-aminopyridines, and 5-aminopyrazoles were studied. Alkenes 2a, b can serve as precursors of aminopyrazoles, pyrimidines, pyrido[1,2-a]pyrimidines, and pyrazolo[1,5-a]pyrimidines modified with the fluoroalkyl and diethoxyphosphoryl groups. Intermediates of some heterocyclization reactions were detected by NMR spectroscopy. The structures of the compounds were confirmed by X ray diffraction analysis.

Full text of DOI:10.1007/s11172-005-0073-2

2060
Russian Chemical Bulletin, International Edition, Vol. 53, No. 9, pp. 2060—2070, September, 2004
Heterocyclization of 2ꢀchloroꢀ1ꢀcyanoꢀ1ꢀdiethoxyphosphorylꢀ
2ꢀtrifluoromethylethylene and 2ꢀchloroꢀ2ꢀchlorodifluoromethylꢀ
1ꢀcyanoꢀ1ꢀdiethoxyphosphorylethylene
A. F. Shidlovskii,ꢀ A. S. Peregudov, B. B. Averkiev, M. Yu. Antipin, and N. D. Chkanikovꢀ
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Fax: +7 (095) 135 6489. Eꢀmail: nchkan@ineos.ac.ru
The reactions of 2ꢀchloroꢀ1ꢀcyanoꢀ1ꢀdiethoxyphosphorylꢀ2ꢀtrifluoromethylethylene (2a)
and 2ꢀchloroꢀ2ꢀchlorodifluoromethylꢀ1ꢀcyanoꢀ1ꢀdiethoxyphosphorylethylene (2b) with
arylamines, arylhydrazines, amidines, 2ꢀaminopyridines, and 5ꢀaminopyrazoles were studied.
Alkenes 2a,b can serve as precursors of aminopyrazoles, pyrimidines, pyrido[1,2ꢀa]pyrimidines,
and pyrazolo[1,5ꢀa]pyrimidines modified with the fluoroalkyl and diethoxyphosphoryl groups.
Intermediates of some heterocyclization reactions were detected by NMR spectroscopy. The
structures of the compounds were confirmed by Xꢀray diffraction analysis.
Key words: 2ꢀchloroꢀ1,1ꢀdicyanoꢀ2ꢀtrifluoromethylethylene, 2ꢀchloroꢀ1ꢀcyanoꢀ1ꢀdiꢀ
ethoxyphosphorylꢀ2ꢀtrifluoromethylethylene, 2ꢀchloroꢀ2ꢀchlorodifluoromethylꢀ1ꢀcyanoꢀ1ꢀ
diethoxyphosphorylethylene, aminopyrazoles, pyrimidines, pyrido[1,2ꢀa]pyrimidines, pyrꢀ
azolo[1,5ꢀa]pyrimidines, heterocyclization, Xꢀray diffraction analysis.
Scheme 1
2ꢀChloroꢀ1,1ꢀdicyanoꢀ2ꢀtrifluoromethylethylene (1)
serves as a convenient precursor of trifluoromethylꢀsubꢀ
stituted derivatives of pyrazole,1a,b quinoline,1b pyrimiꢀ
dine,1c coumarin,1d and pyrido[1,2ꢀa]pyrimidine.1e In the
present study, we examined the possibility of using
2ꢀchloroꢀ1ꢀcyanoꢀ1ꢀdiethoxyphosphorylꢀ2ꢀtrifluoromeꢀ
thylethylene (2a) and 2ꢀchloroꢀ2ꢀchlorodifluoromethylꢀ
1ꢀcyanoꢀ1ꢀdiethoxyphosphorylethylene (2b) as precursors
of heterocyclic compounds modified with both the fluoroꢀ
alkyl and diethoxyphosphoryl groups. In our opinion, this
problem is of interest in the context of research on bioꢀ
logical activities of fluorineꢀcontaining heterocycles2 and
a search for new biologically active phosphonates.3 Only
alkene 2a has been described in the literature.4 However,
we found no data on the reactivity of 2a.
X = F (a), Cl (b)
geometric isomers was made based on the 19F NMR specꢀ
trum. The signal for the fluorine atom in the E isomer
appears as a doublet with the spinꢀspin coupling constant
4JF,P = 2.0 Hz, whereas the signal for this atom in the
Z isomer appears as a singlet.
Compounds 2a and 2b, like 2ꢀchloroꢀ1,1ꢀdicyanoꢀ2ꢀ
trifluoromethylethylene (1), react with arylamines already
at room temperature to form 2ꢀarylaminoꢀ1ꢀcyanoꢀ1ꢀ
diethoxyphosphorylꢀ2ꢀpolyfluoroalkylethylenes 3a—g and
4a—g in high yields (Scheme 2, Table 1). High reactivity
of vinyl chlorides 2a and 2b is, evidently, explained by a
twoꢀstep scheme of the reaction with amines involving
the addition of amine to highly electrophilic acrylonitrile
Results and Discussion
2ꢀChloroꢀ2ꢀchlorodifluoromethylꢀ1ꢀcyanoꢀ1ꢀdiꢀ
ethoxyphosphorylethylene (2b) was prepared analogously
to trifluoromethylꢀsubstituted alkene 2a by condensation
of methyl chlorodifluoroacetate with diethoxyphosphorylꢀ
acetonitrile followed by the replacement of the hydroxy
group of the enolate that formed by the chlorine atom
under the action of phosphorus pentachloride (Scheme 1).
Like alkene 2a, its chlorodifluoromethyl analog 2b
was prepared as a mixture of Z,E isomers in a ratio
E : Z = 5 : 1 (for 2a, E : Z = 4.8 : 1). The assignment of the
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1977—1986, September, 2004.
1066ꢀ5285/04/5309ꢀ2060 © 2004 Springer Science+Business Media, Inc.

Reactions of polyfluoroalkyl vinylphosphonates
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 9, September, 2004
2061
Table 1. Physicochemical characteristics of compounds 3a—g
and 4a—g
derivatives 2a and 2b followed by elimination of hydrogen
chloride to form enamines 3 and 4, respectively.
Comꢀ
pound
R1
R2
R3
Yield
(%)
M.p.
/°С
Scheme 2
3а
3b
3c
3d
3e
3f
3g
4а
4b
4c
4d
4e
4f
H
H
H
H
H
H
H
71
61
62
76.5
118
99
74
76
75
77
OMe
OPh
H
H
Me
Cl
74.5
61.5
83.5
84
70
79
77.5
78.6
81
79
75
—(CH=CH—)2
Cl
H
H
H
H
H
Cl
H
H
H
H
H
H
OMe
OPh
H
H
Me
Cl
96
—(CH=CH—)2
140.5
115.5
75
Cl
H
H
Cl
H
H
42
79
4g
96
The overall view of molecule 3b is shown in Fig. 1.
The central nitrogen atom, N(2), has a planar configuraꢀ
tion (the sum of the bond angles is 360(3)°). According to
the structural formula, this atom can be involved in conꢀ
jugation with both the phenyl fragment and the C(6)=C(7)
double bond. Analysis of the molecular geometry demonꢀ
strates that the N(2) atom is involved in conjugation only
with the double bond, because the N(2)—C(7) bond length
is 1.337(4) Å, whereas the N(2)—C(10) bond length is
1.446(4) Å. The angle between the planes of the valence
bonds about the N(2) and C(7) atoms is 8(2)°, whereas
the angle between the plane of the benzene ring and the
plane of the bonds about the N(2) atom is 82(1)°.
The benzene ring is almost perpendicular to the plane
of the conjugated system involving the N(2), C(7), and
C(6) atoms. The angle between the mean plane passing
through the N(2), C(6), C(7), C(8), C(9), and P(1) atoms
and the plane of the benzene ring is 89.6(1)°. This orienꢀ
tation is determined by the presence of forced nonbonded
contacts with the trifluoromethyl group (C(15)...F(2),
2.949(4) Å; C(11)...F(3), 3.076(4) Å), whose lengths are
Unlike alkenes 2a and 2b existing as mixtures of two
stereoisomers (readily interconvertable), enamines 3 and 4
derived from these compounds exist exclusively as the
Z isomer, which is, apparently, thermodynamically more
stable due to intramolecular hydrogen bonding. The forꢀ
mation of the Z isomers and the presence of a hydrogen
bond were confirmed by the results of Xꢀray diffraction
analysis of compound 3b and NMR spectroscopic studꢀ
ies. The 19F NMR spectra of compounds 3 and 4 have a
singlet with a width at half height of 1 Hz. It is known4
that the cis arrangement of the trifluoromethyl and
4
phosphonate groups is characterized by JF,P = 2.0 Hz.
Consequently, the trifluoromethyl and phosphonate
groups in compounds 3 and 4 are in the trans arrangement.
F(1)
F(2)
N(1)
C(8)
C(4)
C(9)
C(6)
O(4)
C(15)
C(3)
C(14)
C(13)
C(5)
C(7)
F(3)
C(10)
P(1)
O(2)
N(2)
O(3)
C(1)
O(1)
C(12)
C(11)
C(2)
Fig. 1. Overall view of molecule 3b.

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Shidlovskii et al.
N(2)
H(2)
P(1)
O(2)
H(2A)
O(2A)
P(1A)
N(2A)
Fig. 2. Hydrogen bond network in the structure of 3b.
Scheme 3
smaller than the sum of the van der Waals radii of these
atoms (3.17 Å).5 This orientation of the trifluoromethyl
group gives rise to the intramolecular F(1)...C(8) contact
(2.516(4) Å), which prevents the trifluoromethyl group
from being rotated in spite of the fact that this group is
generally disordered. An analogous effect is observed, for
example, in the 7ꢀaminoꢀ2ꢀ(4ꢀchlorophenyl)ꢀ6ꢀdiethoxyꢀ
phosphorylꢀ5ꢀtrifluoromethylpyrazolo[1,5ꢀa]pyrimidine
molecule (see below), in which the trifluoromethyl group
is also not disordered due to the presence of intramolecuꢀ
lar contacts, and has also been noted in the earlier reꢀ
search.6
It should be noted that there is the intramolecular
N(2)—H(2)...O(2) hydrogen bond (N...O, 2.762(4) Å;
H...O, 2.01(4) Å; N—H...O, 145(4)°) in molecule 3b.
These atoms are also involved in the weaker intermolecuꢀ
lar N(2)—H(2)...O(2) hydrogen bond (–x + 1, –y, –z + 2)
(N...O, 3.091(4) Å; H...O, 2.48(4) Å; N—H...O, 128(4)°;
see Fig. 2). In the crystal packing, the H(15A) atom (at
the C(15) atom of the benzene ring) forms a shortened
contact with the O(1) atom of the methoxy group (C...O,
3.423(4) Å; H...O, 2.54 Å; C—H...O, 158°).
Like 2ꢀchloroꢀ1,1ꢀdicyanoꢀ2ꢀtrifluoromethylethylꢀ
ene (1), compounds 2a and 2b react with arylhydrazines
to give 5ꢀaminopyrazole derivatives 5a—g and 6a—d
(Scheme 3, Table 2).
The conditions of this reaction are more drastic than
those of the reaction with alkene 1. For the reaction of
alkene 2a with 2,6ꢀdichloroꢀ4ꢀtrifluoromethylphenylꢀ
hydrazine to be brought to completion, prolonged refluxꢀ
ing (16—20 h) in carbon tetrachloride is required, whereas
the reaction of dicyanoethylene 1 with 2,6ꢀdichloroꢀ4ꢀ
trifluoromethylphenylhydrazine is completed at room
temperature in several hours. The chlorine atom is rapidly
replaced with the primary amino group of arylhydrazines
X = F (2a, 5), Cl (2b, 6)
to give products, which are slowly transformed into
5ꢀaminoꢀ1ꢀarylꢀ4ꢀdiethoxyphosphorylꢀ3ꢀpolyfluoroalkylꢀ

Reactions of polyfluoroalkyl vinylphosphonates
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 9, September, 2004
2063
Table 2. Physicochemical characteristics of compounds 5a—g
and 6a—d
Table 3. Physicochemical characteristics of compounds 9a—d
Comꢀ
pound
R1
R2
R3
Yield
(%)
M.p.
/°С
Comꢀ
pound
R1
R2
R3
R4
Yield
(%)
M.p.
/°С
9a
9b
9c
9d
H
H
Me
H
H
H
H
Me
H
Me
H
40
22
74
53.5
89
75
81
67
5а
5b
5c
5d
5e
5f
5g
6a
6b
6c
6d
H
H
H
Cl
H
Cl
H
H
H
H
Cl
H
H
Cl
H
H
H
H
H
H
H
H
H
Cl
H
H
CF3
CF3
NO2
H
Cl
CF3
CF3
H
H
H
H
H
Cl
H
H
H
H
Cl
44
76
63
71
56
55
67
62
41
37
35
*
*
*
*
H
*
139.5
130.5
*
*
*
*
2ꢀaminopyridines proceeds at the exocyclic nitrogen atom
of the amidine system and is accompanied by intramoꢀ
lecular cyclization of the nitrile group at the endocyclic
nitrogen atom. 2ꢀChloroꢀ1ꢀcyanoꢀ1ꢀdiethoxyphosphorylꢀ
2ꢀtrifluoromethylethylene (2a) reacts analogously to give
substituted pyrido[1,2ꢀa]pyrimidines 9a—d in 20—75%
yields (Scheme 5, Table 3). The reaction of sterically
hindered 2ꢀaminoꢀ6ꢀmethylpyridine with alkene 2a stops
at enamine 10 and is not accompanied by intramolecular
cyclization. The structure of compound 10 was confirmed
by 1H NMR spectroscopy as well as by the fact that its IR
spectrum shows an absorption band at 2200 cm–1 characꢀ
teristic of the nitrile group. Enamine 10 is slowly hydroꢀ
lyzed in air to give 6ꢀmethylꢀ2ꢀtrifluoroacetylaminoꢀ
pyridine and diethoxyphosphorylacetonitrile.
* The amorphous compound.
pyrazoles (5 and 6). In the case of the 2,6ꢀdichloroꢀ4ꢀ
trifluoromethylphenylhydrazine derivative, the formation
of intermediate enamine 7 (see Scheme 3) was detected
by NMR monitoring (see the Experimental section). Cyꢀ
clization to 5ꢀaminopyrazole derivatives 5 and 6 is, apꢀ
parently, hindered due to intramolecular hydrogen bondꢀ
ing between the oxygen atom of the diethoxyphosphoryl
group and the hydrogen atom of the amino group of the
intermediate enamine. This assumption can be made based
on the aboveꢀmentioned data for the Z isomers of stable
enamines 3 and 4.
Scheme 5
We also studied the reactions of cyanoethylene 2a with
amidines and amidineꢀcontaining heterocycles. The reꢀ
actions of 2a with acetamidine and benzamidine at 20 °C
afforded 4ꢀaminoꢀ5ꢀdiethoxyphosphorylꢀ6ꢀtrifluoroꢀ
methylpyrimidines 8a—b, which were isolated in moderꢀ
ate (20—40%) yields (Scheme 4). In the 1H NMR spectra
of these pyrimidines, the signal for the NH2 group apꢀ
pears as two singlets at δH 8.81 and 5.67 for 8a and at
δH 8.72 and 6.21 for 8b. Consequently, there is an inꢀ
tramolecular hydrogen bond between the hydrogen atom
of the amino group and the oxygen atom of the diethoxyꢀ
phosphoryl group in compounds 8a,b, like that observed
in enamines 3 and 4.
Scheme 4
The reactions of 5ꢀaminoꢀ1Hꢀpyrazoles with polyꢀ
fluoroalkylꢀsubstituted dicyanochloroethylenes have not
been studied earlier. First, we examined the reaction
with 2ꢀchloroꢀ1,1ꢀdicyanoꢀ2ꢀtrifluoromethylethylene (1).
At room temperature, this reaction afforded pyrazoꢀ
R = Me, (8a), Ph (8b)
Earlier,1e we have demonstrated that the reaction of
2ꢀchloroꢀ1,1ꢀdicyanoꢀ2ꢀtrifluoromethylethylene (1) with

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Russ.Chem.Bull., Int.Ed., Vol. 53, No. 9, September, 2004
Shidlovskii et al.
lo[1,5ꢀa]pyrimidine derivatives 11a—d. The structures of
compounds 11 were determined by 1H and 13C NMR
spectroscopy (the assignment of the signals in the
13C NMR spectra was made based on the data published
in the literature7). The reaction of 5ꢀaminoꢀ3ꢀ(4ꢀchloroꢀ
phenyl)pyrazole with alkene 2a proceeds analogously, alꢀ
though much more slowly, to give pyrazolo[1,5ꢀa]pyrimꢀ
idine 12. Intermediate enamine 13 (Scheme 6) was
detected by NMR monitoring (see the Experimental
section).
The unit cell of compound 12 (Fig. 3) contains two
crystallographically independent molecules (A and B),
which are characterized by virtually identical geometry.
The molecules differ only in the dihedral angle between
the benzene ring and the plane of the bicyclic fragment
(7.5(1)° for A and –11.0(1)° for B) and the orientation of
the ethyl group at the O(3) atom. The conjugation of the
amino group with the bicyclic fragment leads to shortenꢀ
ing of the C(3)—N(4) bond to 1.326(3) Å (1.330(3) Å
in B), which corresponds to the standard value (1.34 Å)
for the C(sp2)—N(sp2) bond length,8 and elongation of
the C(1)—C(3) bond to 1.424(3) Å (1.430(3) Å in B)
compared to the average value (1.38 Å) based on the data
retrieved from the Cambridge Structural Database (CSD)9
(335 pyrimidine fragments). In both independent molꢀ
ecules, there is an intramolecular hydrogen bond between
the amino group and the O(1) atom. The parameters of
this bond are as follows: N...O, 2.712(2) Å; H...O,
2.02(3) Å; N—H...O, 138(2)° for A; and N...O,
2.732(2) Å; H...O, 1.97(3) Å; N—H...O, 143(2)° for B. In
both molecules, the trifluoromethyl group, like that in the
structure of 3b, is ordered. This fact is attributable to the
steric effect. The distances from the F(1) and F(3) atoms
to the O(2) atom (2.760(2) and 2.728(2) Å in molecule A
and 2.727(2) and 2.787(2) Å in molecule B, respectively)
are smaller than the sum of the van der Walls radii of these
atoms (2.99 Å).5
Scheme 6
In the crystal structure of 12, the hydrogen atoms of
the amino group, which are not involved in intramolecuꢀ
lar hydrogen bonding, form the N(4)—H(4B)...O(1´) and
N(4´)—H(4B´)...O(1) (x + 1, y, z) hydrogen bonds with
the O(1) atom of another independent molecule (Fig. 4)
(N...O, 2.879(2) Å; H...O, 2.07(2) Å; N—H...O, 156(2)°
for A; and N...O, 2.858(2) Å; H...O, 2.07(3) Å; N—H...O,
159(3)° for B).
We also attempted to prepare 4ꢀaminoquinoline
derivatives 14 starting from 2ꢀarylaminoꢀ1ꢀcyanoꢀ
1ꢀdiethoxyphosphorylꢀ2ꢀtrifluoromethylethylenes
3
R = H (a), Me (b), 4ꢀOMeC6H4 (c), 4ꢀClC6H4 (d)
(Scheme 7). It is known that heating of 2ꢀarylaminoꢀ1,1ꢀ
C(7)
C(8)
N(4)
O(1)
O(3)
C(13)
C(14)
N(2)
C(3)
Cl(1)
P(1)
N(1)
C(12)
C(15)
O(2)
C(5)
C(1)
C(2)
C(16)
C(11)
C(10)
C(17)
C(6)
C(9)
F(1)
F(3)
C(4)
F(2)
N(3)
Fig. 3. Overall view of molecule 12.

Reactions of polyfluoroalkyl vinylphosphonates
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 9, September, 2004
2065
P(1´)
O(1´)
N(4´A)
H(4´C)
P(1´A)
O(1´A)
N(4´)
H(4´B)
H(4AA)
H(4A)
H(4´D)
H(4´A)
O(1A)
P(1A)
H(4BA)
N(4A)
O(1)
P(1)
H(4B)
N(4)
Fig. 4. Hydrogen bond network in the structure of 12. Symmetrically related molecules generated from two independent molecules by
the translation along the a axis are indicated by thin lines.
dicyanoꢀ2ꢀtrifluoromethylethylenes in diphenyl ether
gave rise to 4ꢀaminoꢀ3ꢀcyanoꢀ2ꢀtrifluoromethylquinoline
derivatives.1b An attempt to apply this procedure to the
synthesis of 3ꢀdiethoxyphosphorylꢀsubstituted 4ꢀaminoꢀ
2ꢀpolyfluoroalkylquinolines 14 was unsuccessful. We also
failed to prepare the target compounds in the presence of
polyphosphoric acid esters.
Experimental
The 1H, 13C, and 31P NMR spectra were recorded on a
Bruker AMXꢀ400 spectrometer operating at 400.13, 100.61, and
160.62 MHz, respectively. The 19F NMR spectra were meaꢀ
sured on a Bruker WPꢀ200SY spectrometer (188.31 MHz).
The H and 13C chemical shifts were determined relative to
1
the residual signal of the deuterated solvent and recalculated
with respect to SiMe4. For the spectra measured with the use of
CCl4 as the solvent, the chemical shifts were determined relative
to the residual signal of D2O as the external standard (4.52 ppm).
The 19F and 31P chemical shifts were determined relative to
CF3COOH and 85% H3PO4, respectively, as the external stanꢀ
dard. The IR spectra (ν/cm–1) were measured on a URꢀ20 specꢀ
trometer.
Scheme 7
The crystals of compounds 3b and 12 were studied by Xꢀray
diffraction analysis. Xꢀray diffraction data for crystals of 3b
and 12 were collected on a SMART CCD 1000 diffractometer
at 110 K. The structures were solved by direct methods and
refined by the fullꢀmatrix leastꢀsquares method. The nonꢀ
hydrogen atoms were refined anisotropically. The hydrogen
atoms in the structure of 12 were revealed from the difference
electron density map and refined isotropically. The coordinates
of the hydrogen atoms in the structure of 3b (except for the
hydrogen atom of the amino group, which was located from the
difference electron density map) were calculated geometrically
and refined using the riding model. The main parameters of the
structure refinement are given in Table 4. All calculations were
carried out using the SHELXTL PLUS program package.10
2ꢀChloroꢀ1,1ꢀdicyanoꢀ2ꢀtrifluoromethylethylene (1) was synꢀ
thesized according to a procedure described earlier.1a
To summarize, we demonstrated that cyanoethylꢀ
enes 2a and 2b containing the diethoxyphosphoryl group,
like 2ꢀchloroꢀ1,1ꢀdicyanoꢀ2ꢀtrifluoromethylethylene (1),
serve as promising precursors of trifluoromethylꢀ or
chlorodifluoromethylꢀsubstituted nitrogenꢀcontaining
heterocycles. The replacement of one cyano group in the
starting alkenes with the diethoxyphosphoryl group leads
to an increase in the reaction time of heterocyclization
with various amino compounds and sometimes hinders
this heterocyclization.
2ꢀChloroꢀ1ꢀcyanoꢀ1ꢀdiethoxyphosphorylꢀ2ꢀtrifluoromethylꢀ
ethylene (2a)4 was prepared as a mixture of Z,E isomers
(E : Z = 4.8 : 1 was established by 19F and 31P NMR spectroꢀ
scopy). The yield was 37%, b.p. 85—90 °C (1 Torr). 19F NMR

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Russ.Chem.Bull., Int.Ed., Vol. 53, No. 9, September, 2004
Shidlovskii et al.
Table 4. Crystallographic characteristics and details of Xꢀray
diffraction study and refinement of the structures of 3b and 12
added dropwise with stirring to a solution of the corresponding
arylhydrazine (2 mmol) in CCl4 (8 mL) at 20 °C. The reaction
mixture was refluxed for 4—16 h. The precipitate that formed
was filtered off and washed with diethyl ether. The solvent was
removed in vacuo. The product was isolated by preparative TLC
on silica gel using a 2 : 1 ethyl acetate—light petroleum mixture
as the eluent. These reactions afforded compounds 5a—g and
6a—e (see Tables 2 and 6).
1ꢀCyanoꢀ2ꢀ[N´ꢀ(2,6ꢀdichloroꢀ4ꢀtrifluoromethylphenyl)hydrꢀ
azino]ꢀ1ꢀdiethoxyphosphorylꢀ2ꢀtrifluoromethylethylene (7). The
product was detected by 1H, 19F, and 31P NMR spectroscopy.
19F NMR (CDCl3), δ: 9.77 (s, 3 F, CF3); 15.10 (s, 3 F, ArCF3).
31P NMR (CDCl3), δ: 13.00 (m, 1 P, P(O)(OEt)2). 1H NMR
(CDCl3), δ: 1.34 (t, 6 H, OCH2CH3, J = 7.2 Hz); 4.23 (m, 4 H,
OCH2CH3); 7.53 and 10.19 (both s, 1 H each, NH—NH); 7.60
(s, 2 H, Ar).
Reaction of 2ꢀchloroꢀ1ꢀcyanoꢀ1ꢀdiethoxyphosphorylꢀ2ꢀtriꢀ
fluoromethylethylene (2a) with amidines. A solution of 2ꢀchloroꢀ
1ꢀcyanoꢀ1ꢀdiethoxyphosphorylꢀ2ꢀtrifluoromethylethylene (2a)
(0.95 mmol) in acetonitrile (2 mL) was added dropwise with
stirring to a solution of the corresponding amidine (1.8 mmol) in
acetonitrile (3 mL) at 0—10 °C. The reaction mixture was stirred
at 20 °C for 3 h. The solvent was removed in vacuo and the
residue was washed with water. The product was isolated by
preparative TLC on silica gel using a 2 : 1 ethyl acetate—light
petroleum mixture as the eluent. These reactions afforded comꢀ
pounds 8a—b.
4ꢀAminoꢀ5ꢀdiethoxyphosphorylꢀ2ꢀphenylꢀ6ꢀtrifluoromethylꢀ
pyrimidine (8a). The yield was 42%, m.p. 51 °C. Found (%):
C, 47.87; H, 4.55; N, 11.30. C15H17F3N3OP. Calculated (%):
C, 48.01; H, 4.57; N, 11.20. 19F NMR (CCl4), δ: 12.72 (s, 3 F,
CF3). 31P NMR (CCl4), δ: 18.47 (s, 1 P, P(O)(OEt)2). 1H NMR
(CCl4), δ: 1.21 (t, 6 H, OCH2CH3, J = 7.2 Hz); 3.95 and 4.02
(both m, 2 H each, OCH2CH3); 5.67 and 8.81 (both br.s,
1 H each, NH2); 7.23—8.25 (m, 9 H, Ar).
Parameter
3b
12
Molecular formula C15H18F3N2O4P
C17H17ClF3N4O3P
448.77
Molecular weight
Crystal system
Space group
a/Å
b/Å
c/Å
378.28
Monoclinic
P21/n
8.021(3)
19.932(7)
11.361(5)
90
Triclinic
P–1
6.745(2)
12.730(3)
22.771(6)
77.259(5)
88.392(5)
86.487(6)
1903.2(8)
4
α/deg
β/deg
100.47(1)
90
1786(1)
4
2.05
1.407
γ/deg
V/Å3
Z
µ(MoꢀKα)/cm–1
dcalc/g cm–3
2θmax/deg
3.41
1.566
60
52
Number of reflections
Number of independent
reflections
15767
3517
22838
11019
Rint
0.0383
2040
0.0343
7428
Number of reflections
with I ≥ 2σ(I )
Number of parameters
R [F 2 ≥ 2σ(F 2)]
wR (F 2), all data
242
0.0668
0.1502
655
0.1321
0.0509
4
(without a solvent), δ: E isomer: 14.83 (d, 3 F, CF3, JF,P
=
1.9 Hz); Z isomer: 11.70 (s, 3 F, CF3). 31P NMR (without a
solvent), δ: E isomer: 2.57 (br.s, 1 P, P(O)(OEt)2); Z isomer:
4.36 (s, 1 P, P(O)(OEt)2).
2ꢀChloroꢀ2ꢀchlorodifluoromethylꢀ1ꢀcyanoꢀ1ꢀdiethoxyphosꢀ
phorylethylene (2b) was prepared analogously to 2a as a mixture
of Z,E isomers (E : Z = 5.0 : 1 was established by 19F and
31P NMR spectroscopy). The yield was 30%, b.p. 100—103 °C
(1 Torr). 19F NMR (CDCl3), δ: E isomer: 25.59 (d, 3 F, CF3,
4JF,P = 2.0 Hz); Z isomer: 21.96 (s, 3 F, CF3). 31P NMR
(CDCl3), δ: E isomer: –1.25 (br.s, 1 P, P(O)(OEt)2); Z isomer:
0.66 (s, 1 P, P(O)(OEt)2). 31P NMR (CDCl3), δ: a mixture
of Z,E isomers: 1.43 (m, 6 H, OCH2CH3); 4.32 (m, 4 H,
OCH2CH3).
Reaction of alkenes 2a and 2b with arylamines. A solution of
2ꢀchloroꢀ1ꢀcyanoꢀ1ꢀdiethoxyphosphorylꢀ2ꢀtrifluoromethylꢀ
ethylene (2a) or 2ꢀchloroꢀ2ꢀchlorodifluoromethylꢀ1ꢀcyanoꢀ1ꢀ
diethoxyphosphorylethylene (2b) (1.5 mmol) in diethyl ether
(5 mL) was added dropwise with stirring to a solution of the
corresponding arylamine (3 mmol) in diethyl ether (10 mL) at
20 °C. The reaction mixture was stirred at 20 °C for 3 h. The
precipitate that formed was filtered off and washed with diethyl
ether. The solvent was removed in vacuo and the residue was
washed with water and light petroleum. The product was dried
on a filter. These reactions afforded compounds 3a—g and 4a—g
(see Tables 1 and 5)
4ꢀAminoꢀ5ꢀdiethoxyphosphorylꢀ2ꢀmethylꢀ6ꢀtrifluoromethylꢀ
pyrimidine (8b). The yield was 20%, m.p. 75 °C. Found (%):
C, 38.99; H, 4.85; N, 13.42. C10H15F3N3OP. Calculated (%):
C, 38.85; H, 4.83; N, 13.42. 19F NMR (CCl4), δ: 12.77 (s, 3 F,
CF3). 31P NMR (CCl4), δ: 18.14 (s, 1 P, P(O)(OEt)2). 1H NMR
(CCl4), δ: 1.18 (t, 6 H, OCH2CH3, J = 7.2 Hz); 2.31 (s, 3 H,
Me); 3.91 and 3.96 (both m, 2 H each, OCH2CH3); 6.21 and
8.72 (both br.s, 1 H each, NH2).
Reaction of 2ꢀchloroꢀ1ꢀcyanoꢀ1ꢀdiethoxyphosphorylꢀ2ꢀtriꢀ
fluoromethylethylene (2a) with 2ꢀaminopyridines. A solution of
compound 2a (0.68 mmol) in acetonitrile (1.5 mL) was added
dropwise with stirring to a solution of the corresponding
2ꢀaminopyridine (1.36 mmol) in acetonitrile (4 mL) at 0—10 °C.
The reaction mixture was stirred at 20 °C for 2—3 h. The preꢀ
cipitate that formed was filtered off and washed with acetoniꢀ
trile. The solvent was removed in vacuo. The product was isoꢀ
lated by preparative TLC on silica gel using a 2 : 1 ethyl acꢀ
etate—light petroleum mixture as the eluent. These reactions
afforded compounds 9a—d (see Tables 3 and 7).
1ꢀCyanoꢀ1ꢀdiethoxyphosphorylꢀ2ꢀ[2ꢀ(6ꢀmethylpyridyl)]ꢀ2ꢀ
trifluoromethylethylene (10). A solution of 2ꢀchloroꢀ1ꢀcyanoꢀ1ꢀ
diethoxyphosphorylꢀ2ꢀtrifluoromethylethylene (2a) (0.3 g,
1.03 mmol) in acetonitrile (1.5 mL) was added dropwise with
stirring to a solution of 2ꢀaminoꢀ6ꢀmethylpyridine (0.21 g,
1.94 mmol) in acetonitrile (4 mL) at 0—10 °C. The reaction
mixture was stirred at 20 °C for 3 h. The precipitate that formed
Reaction of alkenes 2a and 2b with arylhydrazines. A solution
of 2ꢀchloroꢀ1ꢀcyanoꢀ1ꢀdiethoxyphosphorylꢀ2ꢀtrifluoromethylꢀ
ethylene (2a) or 2ꢀchloroꢀ2ꢀchlorodifluoromethylꢀ1ꢀcyanoꢀ1ꢀ
diethoxyphosphorylethylene (2b) (1 mmol) in CCl4 (3 mL) was

Reactions of polyfluoroalkyl vinylphosphonates
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 9, September, 2004
2067
1
Table 5. H, 19F, and 31P NMR spectra (CDCl3, δ, J/Hz) and results of elemental analysis for compounds 3a—g and 4a—g
Comꢀ
poꢀ
und
1H NMR
δ
δ
Found
Molecular
formula
F
P
(%)
N
(s, CF2X) (s, P(O)(OEt)2)
Calculated
C
H
3a 1.45 (t, 6 H, OCH2CH3, J = 7.2); 4.27 (m, 4 H,
OCH2CH3); 7.14 (d, 2 H, Ar, J = 7.5); 7.30—7.40 (m,
3 H, Ar); 10.71 (br.s, 1 H, NH)
3b 1.45 (t, 6 H, OCH2CH3, J = 7.2); 3.82 (s, 3 H,
OMe); 4.26 (m, 4 H, OCH2CH3); 6.87, 7.06 (both d,
2 H each, Ar, J = 8.7); 10.60 (br.s, 1 H, NH)
3c 1.45 (t, 6 H, OCH2CH3, J = 7.2); 4.27 (m, 4 H,
OCH2CH3); OCH2CH3); 6.96—7.40 (m, 9 H, Ar);
10.65 (br.s, 1 H, NH)
18.61
18.43
18.33
17.90
17.03
16.03
16.40
16.11
16.21
14.94
48.30 4.63 7.98
48.28 4.63 8.04
C14H16F3N2O3P
C15H18F3N2O4P
C20H20F3N2O4P
C18H18F3N2O3P
C14H14Cl2F3N2O3P
47.90 4.95 7.59
47.63 4.80 7.41
54.39 4.48 6.49
54.55 4.58 6.36
3d 1.50 (t, 6 H, OCH2CH3, J = 7.2); 4.34 (m, 4 H,
OCH2CH3); 7.27—7.92 (m, 7 H, Ar);
53.80 4.55 6.97
54.28 4.55 7.03
10.95 (br.s, 1 H, NH)
3e 1.46 (t, 6 H, OCH2CH3, J = 7.2); 4.29 (m, 4 H,
OCH2CH3); 7.14 (d, 1 H, Ar, J = 7.79); 7.23 (t,
1 H, Ar, J = 7.8); 7.45 (d, 1 H, Ar, J = 7.8);
10.67 (br.s, 1 H, NH)
40.29 3.34 6.72
40.31 3.38 6.72
3f
1.45 (t, 6 H, OCH2CH3, J = 7.2); 2.36 (s, 3 H,
Me); 4.26 (m, 4 H, OCH2CH3); 7.01, 7.16 (both d,
2 H each, Ar, J = 8.1); 10.64 (br.s, 1 H, NH)
18.54
18.81
28.23
28.07
28.16
27.42
27.01
28.17
28.25
16.16
17.81
16.62
16.95
16.54
16.76
15.52
16.88
16.14
50.13 4.98 7.93
49.73 5.01 7.73
C15H18F3N2O3P
3g* 1.62 (t, 6 H, OCH2CH3, J = 7.2); 4.38 (m, 4 H,
OCH2CH3); 7.47, 7.22 (both d, 2 H each, Ar, J = 8.7);
10.77 (br.s, 1 H, NH)
4а 1.46 (t, 6 H, OCH2CH3, J = 7.2); 4.27 (m, 4 H,
OCH2CH3); 7.20 (d, 2 H, Ar, J = 7.8); 7.30—7.40 (m,
3 H, Ar); 10.70 (br.s, 1 H, NH)
4b 1.46 (t, 6 H, OCH2CH3, J = 7.2); 3.82 (s, 3 H,
OMe); 4.27 (m, 4 H, OCH2CH3); 6.87, 7.11 (both d,
2 H each, Ar, J = 8.7); 10.58 (br.s, 1 H, NH)
4c 1.46 (t, 6 H, OCH2CH3, J = 7.2); 4.27 (m, 4 H,
OCH2CH3); 6.97—7.39 (m, 9 H, Ar);
44.08 4.40 7.64
43.94 3.95 7.32
C14H15ClF3N2O3P
C14H16ClF2N2O3P
C15H18ClF2N2O4P
C20H20ClF2N2O4P
C18H18ClF2N2O3P
C14H14Cl3F2N2O3P
C15H18ClF2N2O3P
C14H15Cl2F2N2O3P
46.00 4.40 7.64
4.11 4.42 7.68
45.35 4.66 7.10
45.64 4.60 7.10
53.21 4.55 6.05
52.59 4.41 6.13
10.64 (br.s, 1H, NH)
4d 1.46 (t, 6 H, OCH2CH3, J = 7.2); 4.28 (m, 4 H,
OCH2CH3); 7.31—7.87 (m, 7 H, Ar);
52.10 4.37 6.68
52.12 4.37 6.75
10.85 (br.s, 1 H, NH)
4e 1.47 (t, 6 H, OCH2CH3, J = 7.2); 4.29 (m, 4 H,
OCH2CH3); 7.21—7.48 (m, 3 H, Ar);
38.69 3.15 6.38
38.78 3.25 6.46
10.66 (br.s, 1 H, NH)
4f
1.45 (t, 6 H, OCH2CH3, J = 7.2); 2.37 (s, 3 H,
Me); 4.27 (m, 4 H, OCH2CH3); 7.08, 7.17 (both d,
2 H each, Ar, J = 8.1); 10.64 (br.s, 1 H, NH)
47.77 4.80 7.50
47.57 4.79 7.40
4g 1.39 (t, 6 H, OCH2CH3, J = 7.2); 4.21 (m, 4 H,
OCH2CH3); 7.07, 7.28 (both d, 2 H each, Ar, J = 8.7);
10.58 (br.s, 1 H, NH)
42.13 3.80 7.05
42.13 3.79 7.02
* The spectrum was recorded in CCl4.
was filtered off and washed with acetonitrile. The solvent was
removed in vacuo and the residue was washed with water and
light petroleum. The product was isolated by preparative TLC
on silica gel using a 2 : 1 ethyl acetate—light petroleum mixture
as the eluent. The yield of compound 10 was 0.27 g (77%).
Found (%): C, 46.31; H, 4.72; N, 11.59. C14H17F3N3OP. Calꢀ
culated (%): C, 46.29; H, 4.72; N, 11.57. 19F NMR (CDCl3), δ:
17.74 (s, 3 F, CF3). 31P NMR (CDCl3), δ: 14.36 (s, 1 P,
P(O)(OEt)2). 1H NMR (CDCl3), δ: 1.43 (t, 6 H, OCH2CH3,
J = 7.2 Hz); 2.48 (s, 3 H, Me); 4.24 (m, 4 H, OCH2CH3); 6.83
and 6.99 (both d, 1 H each, H(3), H(5), J = 7.8 Hz); 7.58 (t,
1 H, H(4), J = 7.8 Hz), 10.64 (br.s, 1 H, NH). IR, ν/cm–1: 2900
(NH, broad), 2200 (CN).
In air, compound 10 underwent slow hydrolysis to give 6ꢀmeꢀ
thylꢀ2ꢀtrifluoroacetylaminopyridine (19F NMR (CDCl3), δ: 1.92
(s, 3 F, CF3); 1H NMR (CDCl3), δ: 2.49 (s, 3 H, Me); 6.45—7.59

2068
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 9, September, 2004
Shidlovskii et al.
1
Table 6. H, 19F, and 31P NMR spectra (CDCl3, δ, J/Hz) and results of elemental analysis for compounds 5a—g and 6a—d
Comꢀ
poꢀ
1H NMR
19F NMR
31P NMR
Found
Molecular
formula
(%)
(s, CF2X) (s, P(O)(OEt)2)
Calculated
und
C
H
N
F
Cl
—
5a
1.36 (t, 6 H, OCH2CH3, J = 7.2);
4.10, 4.17 (both m, 2 H each,
OCH2CH3); 5.50 (br.s, 2 H,
NH2); 7.44—7.57 (m, 5 H, Ar)
1.18 (t, 6 H, OCH2CH3, J = 7.2);
3.84, 3.90 (both m, 2 H each,
OCH2CH3); 5.41 (br.s, 2 H,
NH2); 7.31, 7.41 (both d, 2 H each,
Ar, J = 8.7)
14.96
15.39
12.40
14.23
46.10 4.76 11.50
46.29 4.72 11.57
—
C14H17F3N3O3P
5b*
42.19 4.18 10.49 13.86 9.43
42.28 4.05 10.57 14.33 8.91
C14H16ClF3N3O3P
5c*
5d*
5e*
5f
1.18 (t, 6 H, OCH2CH3, J = 7.2);
3.82, 3.86 (both m, 2 H each,
OCH2CH3); 5.42 (br.s, 2 H,
NH2); 7.19—7.49 (m, 4 H, Ar)
1.18 (t, 6 H, OCH2CH3, J = 7.2);
3.86, 3.91 (both m, 2 H each,
OCH2CH3); 5.18 (br.s, 2 H,
NH2); 7.24—7.40 (m, 4 H, Ar)
1.20 (t, 6 H, OCH2CH3, J = 7.2);
4.20, 4.27 (both m, 2 H each,
OCH2CH3); 5.59 (br.s, 2 H,
NH2); 7.96 (s, 4 H, Ar)
15.38
15.42
14.11
14.40
14.14
11.61
9.25
42.54 4.20 10.61 13.99 9.35
42.28 4.05 10.57 14.33 8.91
C14H16ClF3N3O3P
C14H16ClF3N3O3P
C15H16F6N3O3P
42.32 4.14 10.49 14.03 9.71
42.28 4.05 10.57 14.33 8.91
15.40,
15.23
41.76 3.68 9.74 25.71
41.78 3.74 9.74 26.43
—
1.36 (t, 6 H, OCH2CH3, J = 7.2);
4.09, 4.16 (both m, 2 H each,
OCH2CH3); 5.30 (br.s, 2 H,
NH2); 7.79 (s, 2 H, Ar)
14.76,
14.45
35.25 2.71 8.11 20.82 11.53 C15H14Cl2F6N3O3P
36.02 2.82 8.40 22.79 14.18
5g** 1.19 (t, 6 H, OCH2CH3, J = 7.2);
4.02, 4.11 (both m, 2 H each,
OCH2CH3); 5.30 (br.s, 2 H,
NH2); 7.00, 7.72 (both d,
13.07
41.11 3.84 13.71 12.82
41.19 3.95 13.72 13.96
—
C14H16F3N4O5P
2 H each, Ar, J = 8.4)
6a
6b
6c
1.42 (t, 6 H, OCH2CH3, J = 7.2);
4.14, 4.23 (both m, 2 H each,
OCH2CH3); 5.59 (br.s, 2 H,
NH2); 7.50—7.62 (m, 5 H, Ar)
1.42 (t, 6 H, OCH2CH3, J = 7.2);
4.14, 4.23 (both m, 2 H each,
OCH2CH3); 5.59 (br.s, 2 H,
NH2); 7.58 (s, 4 H, Ar)
1.38 (t, 6 H, OCH2CH3, J = 7.2);
4.12, 4.20 (both m, 2 H each,
OCH2CH3); 5.61 (br.s, 2 H,
NH2); 7.75, 7.81 (both d,
29.56
29.35
44.02 4.44 11.14
44.28 4.51 11.07
—
—
—
—
—
—
C14H17ClF2N3O3P
C14H16Cl2F2N3O3P
C15H16ClF5N3O3P
9.88
9.60
40.53 3.97 10.06
40.60 3.89 10.15
15.02 (s,
3 F, CF3);
29.15 (s, 2 F,
CF2Cl)
40.40 3.56 9.46
40.24 3.60 9.39
2 H each, Ar, J = 8.44)
6d
1.43 (t, 6 H, OCH2CH3, J =
7.2); 4.15, 4.23 (both m, 2 H each,
OCH2CH3); 5.44 (br.s, 2 H,
NH2); 7.85 (s, 2 H, Ar)
14.42 (s, 3 F,
CF3);
29.01 (s, 2 F,
CF2Cl)
9.50
34.74 2.74 8.19
34.87 2.73 8.13
—
—
C15H14Cl3F5N3O3P
* The spectrum was recorded in CCl4.
** The spectrum was recorded in C6D6.

Reactions of polyfluoroalkyl vinylphosphonates
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 9, September, 2004
2069
1
Table 7. H, 19F, and 31P NMR spectra (CDCl3, δ, J/Hz) and results of elemental analysis for compounds 9a—d
Comꢀ
poꢀ
1H NMR
δ
δ
Found
Molecular
formula
F
P
(%)
Calculated
und
C
H
N
9а 1.37 (t, 6 H, OCH2CH3, J = 7.2); 2.55 (s, 3 H, Me); 4.17,
4.23 (both m, 2 H each, OCH2CH3); 7.23 (d, 1 H, Ar, J = 8.9);
7.89 (dd, 1 H, Ar, J = 6.0, 8.9); 7.58, 9.54 (both d, 1 H each,
Ar, J = 6.0); 10.01 (br.s, 1 H, NH)
13.10 13.86
44.60 4.38 12.00 C13H15F3N3O3P
44.71 4.33 12.03
9b 1.37 (t, 6 H, OCH2CH3, J = 7.2); 2.55 (s, 3 H, Me); 4.17,
4.23 (both m, 2 H each, OCH2CH3); 7.14 (t, 1 H, Ar, J = 6.8);
7.71, 9.36 (both d, 1 H each, Ar, J = 6.8); 9.91 (br.s, 1 H, NH)
9c 1.36 (t, 6 H, OCH2CH3, J = 7.2); 2.45 (s, 3 H, Me); 4.15,
4.22 (both m, 2 H each, OCH2CH3); 7.72, 7.75 (both d, 1 H each,
Ar, J = 9.1); 9.32 (s, 1 H, Ar); 9.87 (br.s, 1 H, NH)
9d 1.36 (t, 6 H, OCH2CH3, J = 7.2); 2.50 (s, 3 H, Me);
4.15, 4.23 (both m, 2 H each, OCH2CH3); 7.37 (br.s, 1 H, Ar);
7.04, 9.37 (both d, 1 H each, Ar, J = 7.2); 9.87 (s, 1 H, NH)
13.12 14.23
13.12 14.32
13.06 14.16
46.12 4.72 11.45 C14H17F3N3O3P
46.29 4.72 11.57
46.17 4.76 11.51 C14H17F3N3O3P
46.29 4.72 11.57
46.20 4.70 11.64 C14H17F3N3O3P
46.29 4.72 11.57
(m, 3 H, Ar); 15.39 (br.s, 1 H, NH)) and diethoxyphosphorylꢀ
acetonitrile. The structure of the latter was confirmed by 1H and
31P NMR spectroscopy in a special experiment with the addiꢀ
tion of an authentic sample.
dropwise with stirring to a solution of 5ꢀaminoꢀ3ꢀ(4ꢀmethoxyꢀ
phenyl)ꢀ1Hꢀpyrazole (0.24 g, 1.3 mmol) and triethylamine
(0.13 g, 1.3 mmol) in acetonitrile (15 mL) at 20 °C. The reaction
mixture was stirred at 20 °C for 2 h. The precipitate that formed
was filtered off and washed with water and light petroleum. The
product was dried in a desiccator over P2O5 to prepare 0.28 g
of 7ꢀaminoꢀ2ꢀ(4ꢀchlorophenyl)ꢀ6ꢀcyanoꢀ5ꢀtrifluoromethylpyrazoꢀ
lo[1,5ꢀa]pyrimidine (11d). The mother acetonitrile liquor was
concentrated to 1/3 of the initial volume and poured into water.
The precipitate that formed was filtered off and washed with
light petroleum. The product was dried in a desiccator over
P2O5, which gave additionally 0.10 g of compound 11d. The
total yield was 0.38 g (86%), sublim.t. 225 °C. Found (%):
C, 49.90; H, 2.05; F, 16.85; N, 20.74. C14H7F3N5. Calcuꢀ
lated (%): C, 49.80; H, 2.09; F, 16.88; N, 20.74. 19F NMR
(DMSOꢀd6), δ: 9.77 (s, 3 F, CF3). 1H NMR (DMSOꢀd6), δ:
7.37 (s, 1 H, H(3)); 7.59 and 8.13 (both d, 2 H each, Ar, J =
8.8 Hz); 9.25 (s, 2 H, NH2).
7ꢀAminoꢀ2ꢀ(4ꢀchlorophenyl)ꢀ6ꢀdiethoxyphosphorylꢀ5ꢀtriꢀ
fluoromethylpyrazolo[1,5ꢀa]pyrimidine (12). A solution of
2ꢀchloroꢀ1ꢀcyanoꢀ1ꢀdiethoxyphosphorylꢀ2ꢀtrifluoromethylꢀ
ethylene (2a) (0.23 g, 0.79 mmol) in acetonitrile (5 mL) was
added dropwise with stirring to a solution of 5ꢀaminoꢀ3ꢀ
(4ꢀchlorophenyl)ꢀ1Hꢀpyrazole (0.15 g, 0.79 mmol) and triethylꢀ
amine (0.08 g, 0.79 mmol) in acetonitrile (10 mL) at 20 °C. The
reaction mixture was stirred at 20 °C for 7 days. The solvent was
removed in vacuo and the residue was washed with water and
light petroleum. Compound 12 containing a small amount of an
impurity (TLC data) was obtained in a yield of 0.22 g (63%).
Additional purification by preparative TLC on silica gel (ethyl
acetate—light petroleum, 2 : 1, as the eluent) afforded comꢀ
pound 12 in a yield of 0.19 g. The total yield was 55%,
m.p. 128.5 °C. Found (%): C, 45.40; H, 3.66; N, 12.62.
Reaction of 2ꢀchloroꢀ1,1ꢀdicyanoꢀ2ꢀtrifluoromethylethylene
(1) with 5ꢀaminoꢀ1Hꢀpyrazoles. A. A solution of compound 1
(1.6 mmol) in dichloromethane or chloroform (5 mL) was added
dropwise with stirring to a solution of the corresponding
aminopyrazole (3.2 mmol) in dichloromethane or chloroform
(20—30 mL) at 20 °C. The reaction mixture was stirred at 20 °C
for 2—3 h. The precipitate that formed was filtered off and
washed with water and light petroleum. The product was dried
in a desiccator over P2O5. These reactions afforded comꢀ
pounds 11a—c.
7ꢀAminoꢀ6ꢀcyanoꢀ5ꢀtrifluoromethylpyrazolo[1,5ꢀa]pyrimꢀ
idine (11a). The yield was 68%, sublim.t. 195 °C. Found (%):
C, 42.36; H, 1.78; F, 24.97; N, 30.83. C8H4F3N5. Calcuꢀ
lated (%): C, 42.30; H, 1.77; F, 25.09; N, 11.20. 19F NMR
(DMSOꢀd6), δ: 9.75 (s, 3 F, CF3). 1H NMR (DMSOꢀd6), δ:
6.86 (s, 1 H, H(3)); 8.38 (s, 1H, H(2)); 9.40 (s, 2 H, NH2).
13C NMR (DMSOꢀd6), δ: 70.5 (s, C(6)); 101.4 (s, C(3)); 114.2
(s, CN); 121.5 (q, CF3, 1JC,F = 276 Hz); 147.0 (q, C(5), 2JC,F
=
34 Hz); 147.1 (s, C(7)); 148.1 (s, C(2)); 152.6 (s, C(3a)).
7ꢀAminoꢀ6ꢀcyanoꢀ2ꢀmethylꢀ5ꢀtrifluoromethylpyrazoꢀ
lo[1,5ꢀa]pyrimidine (11b). The yield was 53%, sublim.t. 200 °C.
Found (%): C, 44.67; H, 2.51; F, 23.60; N, 29.04. C9H6F3N5.
Calculated (%): C, 44.82; H, 2.51; F, 23.63; N, 29.04. 19F NMR
(DMSOꢀd6), δ: 9.78 (s, 3 F, CF3). 1H NMR (DMSOꢀd6), δ:
2.45 (s, 3 H, Me); 6.64 (s, 1 H, H(3)); 9.16 (s, 2 H, NH2).
7ꢀAminoꢀ6ꢀcyanoꢀ2ꢀ(4ꢀmethoxyphenyl)ꢀ5ꢀtrifluoromethylꢀ
pyrazolo[1,5ꢀa]pyrimidine (11c). The yield was 89%, sublim.t.
235 °C. Found (%): C, 54.07; H, 3.02; F, 16.75; N, 21.01.
C
15H10F3N5O. Calculated (%): C, 54.06; H, 3.02; F, 17.10;
N, 21.01. 19F NMR (DMSOꢀd6), δ: 9.79 (s, 3 F, CF3),).
1H NMR (DMSOꢀd6), δ: 3.83 (s, 3 H, OMe); 7.07 and 8.04
(both d, 2 H each, Ar, J = 8.7 Hz); 7.24 (s, 1 H, H(3)); 9.17
(s, 2 H, NH2).
C
18H21ClF3N4O3P. Calculated (%): C, 46.51; H, 4.55; N, 12.05.
19F NMR (DMSOꢀd6), δ: 14.95 (s, 3 F, CF3). 31P NMR
(DMSOꢀd6), δ: 19.53 (s,
P, P(O)(OEt)2). 1H NMR
1
(DMSOꢀd6), δ: 1.26 (t, 6 H, OCH2CH3, J = 7.2 Hz); 4.10 (m,
4 H, OCH2CH3); 7.33 (s, 1 H, H(3)); 7.59 and 8.13 (both d,
2 H each, Ar, J = 7.8 Hz); 8.78 and 9.54 (both s, 1 H each,
B. A solution of 2ꢀchloroꢀ1,1ꢀdicyanoꢀ2ꢀtrifluoromethylꢀ
ethylene (1) (0.25 g, 1.3 mmol) in acetonitrile (5 mL) was added

2070
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 9, September, 2004
Shidlovskii et al.
3
NH2). 13C NMR (DMSOꢀd6), δ: 21.0 (d, OCH2CH3, JC,P
=
=
2. (a) R. Filler, J. Fluorine Chem., 1986, 33, 361; (b) K. Tanura,
H. Mizukami, K. Maeda, H. Watanabe, and K. Uneyama,
J. Org. Chem., 1993, 58, 32 (and references cited therein).
3. (a) R. Engel, Chem. Rev., 1977, 349; (b) F. Palasios, A. Ochoa
de Renata, and J. Oyarzabal, Tetrahedron, 1999, 5947;
(c) M. R. Harnden, A. Parkin, M. J. Parrat, and R. M.
Perkins, J. Med. Chem., 1993, 36, 1345; (d) A. A. Thomas
and K. B. Sharpless, J. Org. Chem., 1999, 64, 8379; (e) Eur.
Pat. 528,760; Chem. Abstr., 1993, 119, 72837b; (f) Ger.
Pat. 3,736,113; Chem. Abstr., 1990, 112, 112068.
4. Ya. G. Bal´on, B. N. Kozhushko, Yu. A. Paliichuk, and
V. A. Shokol, Zh. Obshch. Khim., 1992, 62, 2530 [Russ. J. Gen.
Chem. USSR, 1992, 62, 2089 (Engl. Transl.)].
7 Hz); 66.2 (d, OCH2CH3, 2JC,P = 4 Hz); 85.5 (d, C(6), 1JC,P
192 Hz); 101.4 (s, C(3)); 125.8 (q, CF3, 1JC,F = 276 Hz); 134.1
and 133.3 (both s, CH, Ar); 139.5 and 135.7 (both s, C, Ar);
151.6 (s, C(2)); 157.3 (d, C(7), 2JC,P = 16 Hz); 160.4 (s, C(3a)).
2ꢀ[3ꢀ(4ꢀChlorophenyl)ꢀ1ꢀcyanoꢀ1Hꢀpyrazolꢀ5ꢀylamino]ꢀ1ꢀ
diethoxyphosphorylꢀ2ꢀtrifluoromethylethylene (13). The product
was detected by 19F and 31P NMR spectroscopy. 19F NMR
(CD3CN), δ: 21.45 (s, 3 F, CF3). 31P NMR (CD3CN), δ: 21.49
(s, 1 P, P(O)(OEt)2).
References
5. A. J. Bondi, J. Phys. Chem., 1964, 68, 441.
6. V. Yu. Tyutin, N. D. Chkanikov, V. N. Nesterov, M. Yu.
Antipin, Yu. T. Struchkov, A. F. Kolomiets, and A. V. Fokin,
Izv. Akad. Nauk, Ser. Khim., 993, 552 [Russ. Chem. Bull.,
1993, 42, 512 (Engl. Transl.)].
7. J. S. Bajwa and P. J. Sykes, J. Chem. Soc., Perkin Trans. 1,
1979, 3085.
8. F. H. Allen, O. Kennard, D. G. Watson, L. Brammer, A. G.
Orpen, and R. Taylor, J Chem. Soc., Perkin Trans. 2,
1987, S1.
1. (a) V. I. Krokhtyak, A. Ya. Il´chenko, and L. M.
Yagupol´skii, Zh. Org. Khim., 1980, 16, 1694 [J. Org. Chem.
USSR, 1980, 16, 1441 (Engl. Transl.)]; (b) V. I. Krokhtyak,
A. Ya. Il´chenko, and L. M. Yagupol´skii, Zh. Org. Khim.,
1981, 17, 268 [J. Org. Chem. USSR, 1981, 17, 219 (Engl.
Transl.)]; (c) A. Ya. Il´chenko, V. I. Krokhtyak, and
L. M. Yagupol´skii, Khim. Geterotsikl. Soedin., 1981, 1680
[Chem. Heterocycl. Compd., 1981, 17, 1236 (Engl. Transl.)];
(d) A. Ya. Il´chenko, R. E. Koval´chuk, V. I. Krokhtyak,
and L. M. Yagupol´skii, Zh. Org. Khim., 1981, 17, 2630
[J. Org. Chem. USSR, 1981, 17, 2348 (Engl. Transl.)];
(e) A. F. Shidlovskii, A. Yu. Sizov, L. N. Kuleshova, V. V.
Nesterov, M. Yu. Antipin, A. S. Peregudov, and N. D.
Chkanikov, Izv. Akad. Nauk, Ser. Khim., 2000, 1261 [Russ.
Chem. Bull., Int. Ed., 2000, 49, 1257].
9. F. H. Allen, Acta Crystallogr., 2002, 58, 380.
10. G. M. Sheldrick, SHELXTLꢀ97, Version 5.10, Bruker AXS
Inc., Madison (WIꢀ53719, USA), 1997.
Received May 31, 2004;
in revised form August 10, 2004