Synthesis and structure of 2-ethoxy- and 2-aminomethylidene-3-fluoroalkyl- 3-oxopropionates

Article abstract of DOI:10.1134/S1070428007070019

Condensation of ethyl 3-polyfluoroalkyl-3-oxopropionates with excess triethyl orthoformate gave ethyl 3-polyfluoroalkyl-2-ethoxymethylidene-3- oxopropionates which reacted with primary aliphatic, aromatic, and heterocyclic amines to form ethyl 2-alkyl(ary

Full text of DOI:10.1134/S1070428007070019

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 7, pp. 945–955. © Pleiades Publishing, Ltd., 2007.
Original Russian Text © M.V. Pryadeina, Ya.V. Burgart, V.I. Saloutin, P.A. Slepukhin, O.N. Kazheva, G.V. Shilov, O.A. D’yachenko, O.N. Chupakhin, 2007,
published in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 7, pp. 951–961.
Synthesis and Structure of 2-Ethoxy- and 2-Aminomethylidene-
3
-fluoroalkyl-3-oxopropionates
a
a
a
a
b
M. V. Pryadeina , Ya. V. Burgart , V. I. Saloutin , P. A. Slepukhin , O. N. Kazheva ,
b
b
a
G. V. Shilov , O. A. D’yachenko , and O. N. Chupakhin
a
Postovskii Institute of Organic Synthesis, Ural Division, Russian Academy of Sciences,
ul. S. Kovalevskoi 20, Yekaterinburg, 620041 Russia
e-mail: saloutin@ios.uran.ru
b
Institute of Chemical Physics Problems, Russian Academy of Sciences,
pr. Akademika Semenova 1, Chernogolovka, Moscow oblast, 142432 Russia
Received November 10, 2006
Abstract—Condensation of ethyl 3-polyfluoroalkyl-3-oxopropionates with excess triethyl orthoformate gave
ethyl 3-polyfluoroalkyl-2-ethoxymethylidene-3-oxopropionates which reacted with primary aliphatic, aromatic,
and heterocyclic amines to form ethyl 2-alkyl(aryl, hetaryl)aminomethylidene-3-polyfluoroalkyl-3-oxopro-
pionates. According to the X-ray diffraction and IR data, the latter exist in the crystalline state as the corre-
sponding E isomers, while in solution (NMR data), as mixtures of Z and E isomers. Condensation of ethyl
2
-ethoxymethylidene-3-oxopropionates with secondary heterocyclic amines (morpholine and pyrrolidine) led
to the formation of 2-morpholino(pyrrolidin-1-yl)methylidene-3-fluoroalkyl-3-oxopropionates which were
shown to exist as Z isomers both in the crystalline state and in solution.
DOI: 10.1134/S1070428007070019
3
-Oxopropionates, including those containing flu-
tion scope of fluorinated 3-oxopropionates in organic
synthesis is based on introduction into their molecules
of additional functional groups. Such modification
should increase the number of potential reaction cen-
ters and give rise to new competing reaction paths. For
example, 3-oxo esters can be modified via introduction
oroalkyl groups, are widely used in synthetic organic
chemistry as convenient precursors of various acyclic,
carbocyclic, and heterocyclic compounds some of
which have found application in industry and medicine
[
1]. A promising approach to extension of the applica-
Scheme 1.
OEt
NRR'
OEt
RR'NH (IIIa–IIIi)
Et O, 20°C
RF
OEt
RF
OEt
RF
(
EtO) CH
2
3
O
O
O
O
O
O
·
·
·
H
Ia–Ic
IIa–IIc
IVa, IVb, V, VI, VIIa, VIIb, VIIIa–VIIIc,
IXa, IXb, X, XIa–XIc, XII
(
EtO) CH, RNH (IIId, IIIe)
3 2
RF
OEt
EtOH, ~80°C
VIIa, VIIIb
O
O
·
·
·
H
Ib, Id
I, II, R
pyridin-2-yl (f), pyrimidin-2-yl (g); RR′N = morpholino (h), pyrrolidin-1-yl (i); IV–X, R′ = H; IV, R = Me, R
V, R = PhCH , R = H(CF ; VI, R = Ph, R = CF ; VII, R = 4-MeC , R = HCF (a), CF (b); VIII, R = 4-MeOC
CF (a), H(CF (b), C (c); IX, R = pyridin-2-yl, R = CF (a), C (b); X, R = pyrimidin-2-yl, R = CF ; XI, RR′N = morpho-
lino, R = CF (a), H(CF (b), C (c); XII, RR′N = pyrrolidin-1-yl, R = CF
F
= CF
3
(a), H(CF
2
)
2
3
(b), C F
7
(c), HCF
2
(d); III, R′ = H, R = Me (a), PhCH
2
(b), Ph (c), 4-MeC
6
H
4
(d), 4-MeOC
6
H
4
(e),
F
= CF (a), C
3
3
F
7
(b);
2
F
2
)
2
F
3
6
H
4
F
2
3
6 4 F
H , R =
3
2
)
2
3
F
7
F
3
3
F
7
F
3
F
3
2
)
2
3
F
7
F
3
.
945

9
46
PRYADEINA et al.
into the 2-position of an alkoxy or aminomethylidene
substituent capable of being involved in further trans-
formations [2]. It is known that nonfluorinated 2-alk-
oxy- and 2-aminomethylidene-3-oxopropionates are
widely used in organic chemistry due to their versatile
synthetic potential. Available information on their fluor-
inated analogs is strongly limited. Jones [3] reported
on the synthesis of ethyl 2-ethoxymethylidene-4,4,4-
trifluoro-3-oxobutanoate for which only analytical data
were given.
CH= protons of (E)-2-arylmethylidene-3-oxopropio-
nates appear in a weaker field relative to the corre-
sponding signals of their Z isomers. An analogous pat-
tern was observed for compound IIa. In such a way we
assigned signals for the E and Z isomers of esters IIb
and IIc. It should be noted that the ratios of the E and
Z isomers of IIa–IIc were approximately equimolar.
2
-Alkyl(aryl, hetaryl)aminomethylidene-3-fluoro-
alkyl-3-oxopropionates IV–XII can be synthesized in
two ways. The first of these is based on the condensa-
tion of 2-ethoxymethylidene-3-oxopropionates IIa–IIc
with amines in diethyl ether at room temperature, and
the second is three-component condensation of 3-oxo
esters I with triethyl orthoformate and the correspond-
ing amine in boiling ethanol (Scheme 1). As amine
component we used primary aliphatic [methylamine
The present work was aimed at synthesizing
2
3
-amino- and 2-ethoxymethylidene-3-polyfluoroalkyl-
-oxopropionates and studying their structure. We have
found that ethyl 3-fluoroalkyl-3-oxopropionates Ia–Ic
react with excess triethyl orthoformate to give ethyl
2
-ethoxymethylidene-3-fluoroalkyl-3-oxopropionates
IIa–IIc (Scheme 1). In the syntheses of nonfluorinated
analogs of II [2] and ethyl 2-ethoxymethylidene-4,4,4-
trifluoro-3-oxobutanoate [3] acetic anhydride was used
to displace the reaction equilibrium via binding of the
liberated ethanol to ethyl acetate. According to our
results, compounds II can be obtained in satisfactory
yields in the absence of acetic anhydride, by heating
(
(
IIIa) and benzylamine (IIIb)], aromatic [aniline
IIIc), p-toluidine (IIId), and p-anisidine (IIIe)], and
heterocyclic amines [2-aminopyridine (IIIf) and
2
-aminopyrimidine (IIIg)] and secondary heterocyclic
amines [morpholine (IIIh) and pyrrolidine (IIIi)]. In
all cases, the products were those formed via conden-
sation of amines III at the ethoxymethylidene frag-
ment of esters II. The first procedure turned out to be
more effective; it allowed preparation of 2-aminometh-
ylidene-3-fluoroalkyl-3-oxopropionates having various
alkyl, aryl, or hetaryl substituents on the nitrogen
atom. The three-component condensation can be ac-
complished only with aromatic amines.
3
-oxo esters Ia–Ic with 4 equiv of triethyl orthoformate
with simultaneous removal of the liberated ethanol by
distillation.
Compounds IIa–IIc are light yellow oily sub-
stances; they were isolated and purified by vacuum
1
19
distillation. The H and F NMR spectra of esters IIa–
IIc in CDCl contained two sets of signals, while all
3
Compounds IVa, IVb, VI, VIIa, VIIb, VIIIb,
VIIIc, IXa, X, and XIa–XIc are crystalline sub-
stances; they were isolated and purified by recrystal-
lization. Oily esters V, VIIIa, IXb, and XII were
purified by column chromatography using chloroform
as eluent.
absorption bands belonging to characteristic groups in
their IR spectra (neat) were broadened. These data led
us to conclude that esters IIa–IIc exist as mixtures of Z
and E isomers differing by orientation of substituents
at the double C=C bond (Scheme 2).
2
-Aminomethylidene-3-oxopropionates IVa, IVb,
Scheme 2.
V, VI, VIIa, VIIb, VIIIa–VIIIc, IXa, IXb, and X can
be regarded as examples of a complex tautomeric
system, for the NH proton therein is fairly labile and is
capable of participating in various tautomeric trans-
formations, as well as in hydrogen bonding (both inter-
and intermolecular). Thus esters IV–X could give rise
to keto–enol and amino–imine tautomerism, and they
can exist as imino ketone (A), imino enol (B) and/or
amino ketone (C) tautomers (Scheme 3). In addition,
tautomer C may be Z or E isomer with respect to
substituent configuration at the double C=C bond.
Isomer Z-C should be stabilized via intramolecular
hydrogen bond with the ester oxygen atom, while in
isomer E-C analogous intramolecular hydrogen bond
OEt
EtO
O
RF
OEt
RF
OEt
O
O
O
Z-II
E-II
The E and Z isomers were distinguished by analysis
of the CH= proton signals in the H NMR spectrum
1
of ester IIa. One CH= signal located at δ 7.73 ppm is
a broadened singlet, presumably due to coupling with
fluorine nuclei in the neighboring trifluoromethyl
group; therefore, this signal was assigned to the Z
isomer. Moreover, as shown in [4, 5], signals from the
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 7 2007

SYNTHESIS AND STRUCTURE OF 2-ETHOXY- AND 2-AMINOMETHYLIDENE-...
947
Scheme 3.
The structure of compounds IVa and VIIa in crys-
tal was established by X-ray analysis. The crystalline
structure of IVa and VIIa is formed by crystallo-
graphically independent molecules (Figs. 1, 2) occupy-
ing a common position. Esters IVa and VIIa in the
crystalline state are s-cis,s-cis conformers of isomer
E-C, where the trifluoroalkyl and ethoxy groups ap-
pear in neighboring positions. As shown in Fig. 1,
translationally identical molecules of VIIa are stacked
along the b crystallographic axis, giving rise to alter-
nating layers along the c axis. The molecule is
approximately planar. The maximal deviations from
R
N
R
N
RF
OEt
RF
OEt
O
O
O
O
·
·
·
H
A
B
R
N
R
N
H
H
·
·
·
·
·
·
RF
O
O
OEt
3
the mean-square plane are 0.03 Å (C ) for the hexagon
1
1
5
2
3
3
8
O
OEt
RF
O
H N C C C O and 0.003 Å (C ) for the benzene
8
13
ring C –C . The dihedral angle between the
Z-B
E-B
1
1
5
2
3
3
8
13
H N C C C O and C –C planes is 4.3°. The intra-
3
1
molecular distance O ··· H is 1.90(3) Å, and the
angles N H O and C O H are 136.5 and 102.7°,
can be formed with participation of the fluoroacyl car-
bonyl group.
1
1
3
3
3
1
3
1
The structure of esters IV–X was studied by IR and
H, F, and C NMR spectroscopy, and X-ray anal-
12
O
F
C
1
19
13
1
3
1
C
H
3
4
1
4
11
8
C
C
ysis. In the IR spectra of compounds IV–X dispersed
in mineral oil we observed strong absorption bands due
to carbonyl stretching vibrations at 1725–1685 and
C
C
C
1
2
N
F
5
C
2
C
9
–1
–1
C
1
668–1632 cm and bands at 3278–3100 cm belong-
10
1
1
C
C
O
5
ing to stretching vibrations of amino group; these data
suggest the presence of tautomer C. The low-fre-
quency shift of the carbonyl absorption band results
from conjugation of the carbonyl groups with the
double C=C bond and intramolecular hydrogen bond-
ing with the amino group. The IR spectra of 0.01 M
H
7
C
2
O
6
C
solutions of compounds IVa and VIIIc in CHCl were
3
characterized by considerable broadening of absorp-
tion bands (see Experimental). Two sets of signals
were present in the H NMR spectra of IVa and VIIIc,
a
1
0
recorded from solutions in CDCl . Signals from
b
3
protons of the amino group and methylidene fragment
appeared in a weak field (δCH ~8.15–9.36, δNH ~9.47–
1
2.60 ppm) as doublets with a coupling constant of
~
14 Hz, which indicates trans arrangement of these
protons. Esters IV–X also showed doubled fluorine
1
9
1
resonance signals in F NMR spectra. The H NMR
spectra of IVa and VI in (CD ) CO, (CD ) SO, and
3
2
3 2
CD OD also contained two sets of signals. Therefore,
3
c
we concluded that esters IV–X in solution exist as
mixtures of Z and E isomers of tautomer C and that in
the crystalline state only one isomer of tautomer C is
present. An exception was oily ester V; according to
the IR data (neat), it is a mixture of Z and E isomers:
the spectrum contains two sets of carbonyl absorption
bands.
Fig. 1. Crystalline structure of ethyl 4,4-difluoro-2-(4-meth-
ylphenylaminomethylidene)-3-oxobutanoate (VIIa) accord-
ing to the X-ray diffraction data.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 7 2007

9
48
PRYADEINA et al.
bon atom is attached to an electron-withdrawing group,
8
and the other, to an electron-donor group. As a result
of electron density delocalization, formally double
carbon–carbon bond in such compounds becomes
partially single, and the barrier to rotation about it
decreases relative to normal olefins [7]. Presumably, in
our case crystallization gives only one conformational
E isomer. Dissolution is accompanied by isomerization
to produce a mixture of Z and E isomers. Probably, the
isomerization involves mesomeric structures shown in
Scheme 4.
C
1
N
1
H
5
C
2
2
3
O
C
O
3
1
C
C
3
4
F
C
1
F
The Z and E isomers in solution were distinguished
1
O
13
on the basis of the C NMR spectra of esters IVa and
6
C
2
VIIb. Analysis of the spectra allowed us to reveal
F
some general relations. The major tautomer is charac-
7
3
C
terized by a quartet signal from the C carbonyl carbon
atom neighboring to the trifluoromethyl group, which
is located in a weaker field, as compared to the corre-
sponding signal of the other isomer (Table 1), while
the opposite pattern is observed for the ester carbonyl
Fig. 2. Structure the molecule of ethyl 4,4,4-trifluoro-2-
methylaminomethylidene)-3-oxobutanoate (IVa) according
to the X-ray diffraction data.
(
1
carbon atom (C ). Taking into account that proton-
donor solvents induce a downfield shift of the carbonyl
carbon signal of acetone [8], we concluded that the
respectively. These data suggest formation of intramol-
3
1
3
1
downfield C signal and upfield C signal belong to the
major E isomer and that the signals arranged in the
reverse order arise from the Z isomer. This assignment
ecular hydrogen bond between O and H . According
to the X-ray diffraction data, molecules IVa are also
approximately planar. The intramolecular distance
3
1
1
1
3
5
O ··· H is 2.03(2) Å, and the angles N H O and
is additionally confirmed by the fact that the C signal
3
3
1
C O H are 132.3 and 101.5°, respectively, indicating
(double-bonded carbon atom) of the Z isomer is
a quartet (JCF ≈ 1.3 Hz for IVa) or broadened singlet
3
1
intramolecular hydrogen bonding O ···H .
(
VIIb) due to long-range coupling with fluorine nuclei
It is known [6, 7] that the barrier to rotation about
a double C=C bond considerably decreases if there
exist neighboring functional groups polarizing that
bond or the latter is a part of a conjugated system. This
is especially typical of enamino ketones and so-called
of the trifluoromethyl group.
1
In the H NMR spectra of esters IVa and VIIb
dissolved in CDCl , protons of the CH and NH groups
3
of the predominant E isomer resonate in a weaker field
relative to those of the Z isomer (see Experimental).
Larger chemical shift of the NH proton in the E isomer
indicate stronger intramolecular hydrogen bond therein
and hence its higher stability. Signals from fluorine
nuclei in the trifluoromethyl group of the Z isomers of
“
push-pull” olefins in which one double-bonded car-
Scheme 4.
R
N
R
N
H
H
1
9
·
·
·
·
·
·
IVa and VIIb appear in the F NMR spectra (CDCl )
in a weaker field relative to the CF signals from the E
3
O
O
O
O
3
isomers in which the trifluoroacetyl group is involved
in intramolecular hydrogen bond. These findings are
consistent with our previous data for fluoroalkyl-con-
taining 1,2,3-triketone 2-arylhydrazones [9]. The above
relations allowed us to assign signals to Z and E
isomers of the other esters (IVb, V, VI, VIIa, VIIIa–
VIIIc, IXa, IXb, and X). Almost all esters turned out
to exist as equilibrium mixtures of Z and E isomers,
the latter prevailing (as more stable).
RF
OEt
RF
OEt
E
R
N
R
N
H
O
H
·
·
·
O
O
O
RF
OEt
RF
OEt
Z
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 7 2007

SYNTHESIS AND STRUCTURE OF 2-ETHOXY- AND 2-AMINOMETHYLIDENE-...
949
13
Table 1. C NMR spectra (CDCl
3
C
) of compounds IVa and VIb, δ , ppm (JCF, Hz)
14
14
CH3
CH3
1
1
11
1
0
12
13
10
9
12
13
9
8
8CH3
N
CH3
8
8
N
N
N
5
5
5
2
5
2
H
H
H
H
·
·
·
·
·
·
·
·
·
·
2
·
·
2
O
O
O
O
O
O
O
O
1
3
1
3
1
3
1
3
4
4
4
4
7
6
O
CF3
7
6
O
CF3
7
6
O
CF3
7
6
O
CF3
CH CH
CH CH
CH CH
CH CH
3
2
3
2
3
2
3 2
E-IVa
Z-IVa
E-VIIb
Z-VIIb
Compound IVa
Compound VIIb
Atom
E
Z
E
Z
1
2
3
4
5
C
C
C
C
C
165.29 s
097.37 s
167.95 s
096.11 s
165.11 s
099.25 s
167.74 s
098.24 s
178.43 q (J = 35.0)
178.46 q (J = 35.5)
177.5 q (J = 34.9)
179.18 q (J = 36.4)
116.92 q (J = 287.5)
155.94 s
117.08 q (J = 287.4)
117.29 q (J = 289.9)
117.12 q (J = 290.0)
154.00 q (J = 1.7)
060.81 s11
020.79 s
164.07 s
162.72 br.s
6
S
060.53 s
060.36 s
060.90 s
7
8
9
C
C
036.78 s
036.52 s
020.85 s
013.94 s
013.78 s
137.19 s
136.55 s
13
C , C
–
–
–
–
–
–
–
–
130.58 s
130.52 s
1
0
12
C , C
118.29 s
117.83 s
1
1
C
C
135.46 s
135.73 s
1
4
013.94 s
013.75 s
We examined isomeric composition of compounds
IVa and VI in different solvents [CDCl , (CD ) CO,
increased rate of rotation about the C–N bond. An
analogous behavior is typical of N,N-dialkyl enamino
ketones and N,N-dialkyl enamino acids [7].
3
3 2
(
CD ) SO, CD OD] and found that the isomer ratio
3 2 3
almost does not depend on the solvent nature. The only
observed effect was variation of the shape of signals.
All signals were clearly resolved in weakly polar
aprotic CDCl , in polar aprotic (CD ) SO all signals
2
-Hetarylmethylidene-substituted 3-oxopropionates
XIa–XIc and XII have no NH group; therefore, they
3
3 2
1
0
C
were broadened, and in polar proton-donor CD OD
3
4
O
all CH= signals appeared as singlets, while signals
from the NH protons were almost absent (due to
exchange). The isomer ratio remained almost constant
with time: the signal intensity ratio did not change in
the NMR spectra recorded at equal time intervals.
Exceptions were esters IXa and X containing hetero-
cyclic fragments. The NMR spectra of these com-
pounds revealed displacement of the equilibrium
toward the Z isomer (Table 2).
11
1
C
9
N
C
3
5
1
O
C
8
C
3
2
C
1
C
F
2
O
4
2
C
C
3
7
F
C
F
1
6
O
C
1
We also examined by H NMR spectroscopy the
isomeric composition of ester IVa in (CD ) SO in the
temperature range from 30 to 100°C. At 70°C, signals
from the Z and E isomers coalesced, presumably due to
3
2
Fig. 3. Structure the molecule of ethyl 4,4,4-trifluoro-2-
morpholinomethylidene)-3-oxobutanoate (XIa) according
to the X-ray diffraction data.
(
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 7 2007

9
50
PRYADEINA et al.
Table 2. E/Z Isomer ratios (%) of compounds IVa, IVb, V,
VI, VIIa, VIIb, VIIIa–VIIIc, IXa, IXb, and X in solution
persed in mineral oil, thin films (neat), or 0.01 M
solutions in chloroform. The H NMR spectra were
1
according to the NMR data (CDCl
3
)
measured on a Bruker DRX-400 spectrometer at
19
4
00 MHz relative to tetramethylsilane. The F NMR
Comp. no.
R
F
R
E
Z
spectra were recorded on Tesla BS-587A (75.3 MHz)
and Bruker DRX-400 instruments (376 MHz) using
IVa
CF
3
Me
Me
CH
Ph
73 (73) 27 (27)
a
13
IVb
C
3
F
7
87
75
65
90
62
67
73
60
13
25
35
10
38
33
27
40
C F as reference. The C NMR spectra were recorded
6
6
H(CF
CF
HCF
2
)
2
2
Ph
on a Bruker DRX-400 spectrometer (100 MHz) rela-
tive to tetramethylsilane. The elemental compositions
were determined on a Carlo Erba CHNS-O EA 1108
analyzer.
V
VI
3
VIIa
2
4-MeC
4-MeC
6
H
H
4
a
VIIb
CF
CF
3
6
4
X-Ray diffraction study of a single crystal of com-
pound VIIa was performed at room temperature on
VIIIa
VIIIb
VIIIc
3
4-MeOC
4-MeOC
4-MeOC
6
6
6
H
4
4
4
H(CF
2
)
2
H
H
an Enraf–Nonius CAD-4 diffractometer (MoK irra-
α
C
3
F
7
diation, graphite monochromator, ω/2θ scanning); and
single crystals of IVa and XIa were analyzed on
b
IXa
CF
3
Pyridin-2-yl
Pyridin-2-yl
71 (66) 29 (44)
44 56
IXb
C
3
F
7
an Xcalibur 3 diffractometer at 295(2) K (MoK ir-
α
b
X
CF
3
Pyrimidin-2-yl 94 (75) 6 (25)
radiation, graphite monochromator, CCD detector,
ω/2θ scanning). The structures were solved by the
direct methods, followed by Fourier synthesis, using
SHELXS-97 software [10] and were refined by the
least-squares procedure in anisotropic full-matrix ap-
proximation for all non-hydrogen atoms using
SHELXL-97 program [10]. The coordinates of hydro-
gen atoms were determined experimentally and were
refined in isotropic approximation.
a
6
In DMSO-d .
b
In parentheses are given the isomer ratios after storage for
0 days at 20°C.
1
could give rise to only Z,E isomerism (Scheme 5).
1
19
However, the H and F NMR spectra of these com-
pounds in CDCl showed that they exist as a single
3
isomer. According to the X-ray diffraction data, ester
The principal crystallographic parameters of com-
pounds IVa, VIIa, and XIa are collected in Table 3;
the complete sets of crystallographic data were depos-
ited to the Cambridge Crystallographic Data Center
XIa in crystal is Z-isomer in s-trans,s-cis conformation
(
Fig. 3). The IR spectra of a crystalline sample of XIa
(
mineral oil) and its solution in CHCl revealed no
3
considerable differences. Therefore, we concluded that
(entry nos. CCDC 612574, CCDC 620487, and CCDC
ester XIa in CDCl also has the structure of Z isomer.
3
1
612575, respectively).
Comparison of the H NMR and IR data for com-
pounds XIa–XIc and XII showed that they have
similar structures. Unlike esters VI–X stabilized by
intramolecular hydrogen bond, compounds XI and XII
are unstable, and they readily undergo decomposition
in chloroform solution on storage.
Ethyl 2-ethoxymethylidene-4,4,4-trifluoro-3-oxo-
butanoate (IIa). A mixture of 9.2 g (0.05 mol) of ester
Ia and 29.6 g (0.2 mol) of triethyl orthoformate was
heated under reflux for 1 h with simultaneous removal
of ethanol by distillation. The mixture was then sub-
jected to fractional distillation under reduced pressure.
Yield 7.1 g (59%), bp 125–127°C (15–17 mm); pub-
lished data [3]: bp 115–120°C (10 mm). IR spectrum
Scheme 5.
–
1
N
O
N
O
(
1
(
film), ν, cm : 2987 (C–H), 1730–1712 (C=O), 1618–
1
580 (C=C), 1202–1108 (C–F). H NMR spectrum
RF
OEt
RF
OEt
CDCl ), δ, ppm: E isomer: 1.32 t and 1.41 t (3H each,
3
OCH CH , J = 7.2 Hz), 4.25 q and 4.30 q (2H each,
O
O
2
3
OCH , J = 7.2 Hz), 7.83 s (1H, CH); Z isomer: 1.29 t
E
Z
2
and 1.45 t (3H each, OCH CH , J = 7.0 Hz), 4.29 q
2
3
and 4.35 q (2H each, OCH , J = 7.0 Hz), 7.73 br.s (1H,
EXPERIMENTAL
The IR spectra were recorded in the range from 400
to 4000 cm on a Perkin–Elmer Spectrum One spec-
trometer with Fourier transform from samples dis-
2
1
9
CH). F NMR spectrum (CDCl ), δ , ppm: 86.16 s
3
F
(CF , E isomer), 89.23 br.s (CF , Z isomer). Found, %:
3
3
–1
C 45.30; H 4.71; F 23.65. C H F O . Calculated, %:
9 11 3 4
C 45.01; H 4.62; F 23.73.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 7 2007

SYNTHESIS AND STRUCTURE OF 2-ETHOXY- AND 2-AMINOMETHYLIDENE-...
951
Table 3. Crystallographic data for compounds IVa, VIIa, and XIa
Parameter
IVa
NO
225.17
Monoclinic
P2 /c
VIIa
NO
283.27
XIa
Formula
C
8
H
10
F
3
3
C
14
H
15
F
2
3
C
11
H
14
F
3
NO
4
Molecular weight
Crystal system
Space group
a, Å
281.23
Triclinic
Triclinic
⎯
⎯
1
P1
P1
10.0923(16)
11.472(3)00
08.8067(13)
90.00
07.983(2)
08.288(1)
12.139(3)
108.02(2)
091.10(2)
114.07(2)
687.5(3)
2
7.9855(16)
8.7560(15)
b, Å
c, Å
10.375(4)000
66.02(2)
89.65(3)
0080.540(15)
652.3(3)
2
α, deg
β, deg
000100.878(14)
90.00
γ, deg
3
V, Å
1001.3(3)
4
Z
λ, Å
0.71073
1.494
0.71073
1.370
0.71073
1.432
3
d
calc, g/cm
–1
μ, cm
0.148
0.114
0.135
Total reflection number
162230
2082
10725
Number of independent reflections
3158
1977
3949
Number of reflections with F
0
> 4σ(F
0
)
1057
1692
1539
Number of parameters
0176
0242
0228
2
θ
max, deg
63.60
46.94
63.44
Range of h
Range of k
Range of l
R-Factor [F
–14 ≤ h ≤ 14
–16 ≤ k ≤ 16
–12 ≤ l ≤ 12
0.039, 0.068
–8 ≤ h ≤ 8
–9 ≤ k ≤ 8
–11 ≤ h ≤ 11
–12 ≤ k ≤ 12
–15 ≤ l ≤ 14
0.0372, 0.0644
000 ≤ l ≤ 13
0
> 4σ(F
0
)], wR
2
0.032, 0.086
Ethyl 2-ethoxymethylidene-3-oxoalkanoates IIb
and IIc were synthesized in a similar way.
Ethyl 2-ethoxymethylidene-4,4,5,5-tetrafluoro-3-
oxopentanoate (IIb) was synthesized from 10.8 g
Ethyl 2-ethoxymethylidene-4,4,5,5,6,6,6-hepta-
fluoro-3-oxohexanoate (IIc) was synthesized from
4.2 g (0.05 mol) of ester Ic. Yield 9.7 g (57%),
1
bp 142–144°C (15–17 mm). IR spectrum (film), ν,
–
1
cm : 2989 (=C–H), 1732–1719 br (C=O), 1621 (C=C),
(
0.05 mol) of ester Ib. Yield 8.9 g (66%), bp 135–
40°C (115–117 mm). IR spectrum (film), ν, cm :
1
–1
1
231–1128 (C–F). H NMR spectrum (CDCl ), δ,
3
1
2
1
ppm: Z isomer (57%): 1.26 t and 1.32 t (3H each,
OCH CH , J = 7.0 Hz), 4.05 q and 4.18 q (2H each,
989 (=C–H), 1725–1711 br (C=O), 1616–1591 (C=C),
1
209–1111 (C–F). H NMR spectrum (CDCl ), δ, ppm:
2
3
3
OCH , J = 7.0 Hz), 8.00 s (1H, CH); E isomer (43%):
E isomer: 1.29 t and 1.39 t (3H each, OCH CH , J =
2
2
3
1
4
(
.17 t and 1.34 t (3H each, OCH CH , J = 7.2 Hz),
7
.2 Hz), 4.24 q and 4.29 q (2H each, OCH , J =
2
3
2
.14 q and 4.37 q (2H each, OCH , J = 7.2 Hz), 8.04 s
7
.2 Hz), 6.27 t.t.t (1H, HCF , J = 52.9, 5.8 Hz), 7.78 s
2
2
1
9
1H, CH). F NMR spectrum (CDCl ), δ , ppm:
(
1H, CH); Z isomer: 1.32 t and 1.44 t (3H each,
3 F
Z isomer (57%): 44.94 m (2F, CF ), 46.68 m (2F, CF ),
2
2
OCH CH , J = 7.2 Hz), 4.27 q and 4.35 q (2H each,
2
3
8
(
8
2.14 t (3F, CF , J = 8.5 Hz); E isomer (43%): 42.17 m
3
OCH , J = 7.2 Hz), 6.24 t.t.t [1H, H(CF ) , J = 53.0,
2
2 2
19
2F, CF ), 47.69 m (2F, CF ), 81.98 t (3F, CF , J =
5
.8 Hz], 7.77 s (1H, CH). F NMR spectrum (CDCl ),
2 2 3
3
.5 Hz). Found, %: C 38.82; H 3.11; F 39.14.
δ , ppm: E isomer: 23.10 d.m (2F, HCF , J = 52.9 Hz),
F
2
C H F O . Calculated, %: C 38.84; H 3.26; F 39.09.
3
7.87 m (2F, CF ); Z isomer: 22.87 d.m (2F, HCF , J =
11 11
7
4
2
2
5
2.9 Hz), 40.79 m (2F, CF ). Found, %: C 42.60;
Ethyl 2-alkyl(aryl, hetaryl)aminomethylidene-3-
oxoalkanoates IV–XII. a. Gaseous methylamine was
passed over a period of 30 min through a solution of
2
H 4.43; F 25.40. C H F O . Calculated, %: C 42.67;
H 4.48; F 25.31.
1
0
12
4
4
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 7 2007

9
0
52
PRYADEINA et al.
.01 mol of the corresponding ethyl 2-ethoxymethyli-
J = 9.8 Hz); Z isomer: 38.80 m (2F, 5-F), 49.39 m (2F,
4-F, J = 9.8 Hz), 82.42 t (3F, 6-F, J = 9.8 Hz). Found,
%: C 36.90; H 3.16; F 40.87; N 4.25. C H F NO .
dene-3-oxoalkanoate II in 10 ml of diethyl ether at
0°C until complete conversion of the initial ester
TLC). The mixture was evaporated, and the residue
2
(
1
0
10
7
3
Calculated, %: C 36.94; H 3.10; F 40.90; N 4.31.
was recrystallized from hexane.
Ethyl (2E)-2-benzylaminomethylidene-4,4,5,5-
tetrafluoro-3-oxopentanoate (V). Yield 2.39 g (72%)
(b), oily substance. IR spectrum (film), ν, cm : 3250
b. A mixture of 0.01 mol of ester II and 0.01 mol of
amine IIIb–IIIi in 10 ml of diethyl ether was stirred at
room temperature for 15–40 min in the synthesis of
esters VI, VIIa, VIIb, VIIIb, XIb, and XIc and for 2–
–1
(N–H); 1705 (C=O, ester); 1645 (C=O, ketone); 1594,
1
1582 (C=C, δN–H); 1267–1091 (C–F). H NMR spec-
4
h in the synthesis of esters IXa–IXb and XII. The
trum (CDCl ), δ, ppm: 7.23–7.43 m (5H, C H );
3
6
5
mixture was evaporated, and the residue was recrystal-
lized from hexane. Compounds V, VIIIa, IXb, XIa,
and XII were purified by flash chromatography on
E isomer: 1.31 t (3H, OCH CH , J = 7.2 Hz), 4.23 q
2
3
(2H, OCH , J = 7.2 Hz), 4.60 d (2H, OCH , J =
2
2
5.9 Hz), 6.68 t.t (1H, HCF , J = 53.8, 5.8 Hz), 8.16 d
2
silica gel (0.063–0.200 mm) using CHCl as eluent.
(1H, CH, J = 14.2 Hz), 10.89 br.s (1H, NH); Z isomer:
3
1
.32 t (3H, OCH CH , J = 7.1 Hz), 4.26 q (2H, OCH ,
c. A mixture of 0.01 mol of ester I, 0.02 mol of
triethyl orthoformate, and 0.01 mol of amine IIId or
IIIe in 15 ml of ethanol was heated for 12 h under
reflux. The mixture was evaporated, and the residue
was recrystallized from hexane.
2
3
2
J = 7.1 Hz), 4.59 d (2H, OCH , J = 5.9 Hz), 6.34 t.t
2
[
1H, H(CF ) , J = 53.3, 6.0 Hz], 8.06 d (1H, CH, J =
2 2
1
9
1
4.2 Hz), 9.80 br.s (1H, NH). F NMR spectrum
(
CDCl ), δ , ppm: E isomer: 23.94 d.t (2F, 5-F, J =
3 F
5
2
3.8, 7.9 Hz), 39.58 m (2F, 4-F, J = 5.8 Hz); Z isomer:
2.09 d.m (2F, 5-F, J = 53.3 Hz), 41.23 m (2F, 4-F,
Ethyl (2E)-4,4,4-trifluoro-2-methylaminometh-
ylidene-3-oxobutanoate (IVa). Yield 1.39 g (62%)
–
1
J = 6.0 Hz). Found, %: C 54.13; H 4.35; F 22.78;
N 4.27. C H F NO . Calculated, %: C 54.22; H 4.35;
F 22.87; N 4.22.
(
a), mp 92–94°C. IR spectrum, ν, cm : in mineral oil:
1
5
14
4
3
3
1
1
1
252 (N–H); 1693 (C=O, ester); 1638 (C=O, ketone);
607, 1582 (C=C, N–H); 1236–1143 (C–F); in CHCl3:
688 v.br (C=O, ester); 1648 br (C=O, ketone); 1602,
Ethyl (2E)-4,4,4-trifluoro-3-oxo-2-(phenylamino-
methylidene)butanoate (VI). Yield 1.58 g (55%) (b),
mp 66–68°C. IR spectrum (mineral oil), ν, cm : 3200,
3150 (N–H); 1715 (C=O, ester); 1644 (C=O); 1601,
1574 (C=C, δN–H); 1188–1125 (C–F). H NMR spec-
1
522 (C=C, δN–H). H NMR spectrum (CDCl ), δ,
3
–1
ppm: E isomer: 1.31 t (3H, OCH CH , J = 7.2 Hz),
2
3
3
.27 d.d (3H, NCH , J = 5.1, 0.6 Hz), 4.24 q (2H,
3
1
OCH , J = 7.2 Hz), 8.15 br.d (1H, CH, J = 14.4 Hz),
2
1
0.53 br.s (1H, NH); Z isomer: 1.33 t (3H, OCH CH ,
trum (CDCl
mer: 1.35 t (3H, OCH
OCH , J = 7.0 Hz), 8.63 d (1H, CH, J = 14.1 Hz),
3
), δ, ppm: 7.46–7.19 m (5H, Ph); E iso-
2
3
J = 7.2 Hz), 3.24 d.d (3H, NCH , J = 5.1, 0.6 Hz),
2
CH , J = 7.0 Hz), 4.30 q (2H,
3
3
4.25 q (2H, OCH , J = 7.2 Hz), 8.03 br.d (1H, CH, J =
2
2
1
9
1
4.4 Hz), 9.63 br.s (1H, NH). F NMR spectrum
12.18 br.d (1H, NH, J = 14.1 Hz); Z isomer: 1.37 t
(
(
CDCl ), δ , ppm: 89.15 s (CF , E isomer), 90.07 s
(3H, OCH CH , J = 7.1 Hz), 4.33 q (2H, OCH , J =
3 F 3
2
3
2
CF , Z isomer). Found, %: C 42.60; H 4.46; F 25.59;
7.1 Hz), 8.49 d (1H, CH, J = 14.1 Hz), 11.38 br.d (1H,
3
1
9
N 6.23. C H F NO . Calculated, %: C 42.67; H 4.48;
NH, J = 14.1 Hz). F NMR spectrum (CDCl ), δ ,
8
10
3
3
3 F
F 25.31; N 6.22.
ppm: 89.03 s (CF , E isomer), 89.98 s (CF , Z isomer).
3 3
Found, %: C 54.50; H 4.26; F 19.95; N 4.87.
C H F NO . Calculated, %: C 54.36; H 4.21;
F 19.84; N 4.88.
Ethyl (2E)-4,4,5,5,6,6,6-heptafluoro-2-methyl-
aminomethylidene-3-oxohexanoate (IVb). Yield
1
3
12
3
3
1
.75 g (54%) (a), mp 104–105°C. IR spectrum (miner-
–1
al oil), ν, cm : 3250 (N–H); 1695 (C=O, ester); 1640
Ethyl (2E)-4,4-difluoro-2-(4-methylphenyl-
aminomethylidene)-3-oxobutanoate (VIIa). Yield
1.89 g (67%) (c), mp 89–90°C. IR spectrum (mineral
(
C=O); 1600, 1578 (C=C, δN–H); 1270–1116 (C–F).
1
H NMR spectrum (DMSO-d ), δ, ppm: E isomer:
6
–
1
1
.25 t (3H, OCH CH , J = 7.0 Hz), 4.11 q (2H, OCH ,
oil), ν, cm : 3120 (N–H); 3000 (C–H); 1690 (C=O,
2
3
2
J = 7.0 Hz), 8.09 d (1H, CH, J = 14.1 Hz), 10.42 br.s
ester); 1640 (C=O, ketone); 1600, 1570 (C=C, δN–H);
1
(
1H, NH); Z isomer (13%): 1.27 t (3H, OCH CH , J =
1100–1030 (C–F). H NMR spectrum (CDCl ), δ,
2
3
3
7
.0 Hz), 3.67 q (2H, OCH , J = 7.0 Hz), 7.97 d (1H,
ppm: 7.12–7.15 m, 7.23–7.25 m (2H, C H ); E isomer:
2
6
4
1
9
CH, J = 14.1 Hz), 9.47 br.s (1H, NH). F NMR
spectrum (DMSO-d ), δ , ppm: E isomer: 39.06 m (2F,
1.36 t (3H, OCH CH , J = 7.1 Hz), 2.36 s (3H, CH ),
2
3
3
4.33 q (2H, OCH , J = 7.1 Hz), 6.88 (1H, HCF , J =
6
F
2
2
5
-F), 49.39 m (2F, 4-F, J = 9.8 Hz), 82.55 t (3F, 6-F,
54.5 Hz), 8.58 d (1H, CH, J = 13.9 Hz), 12.60 br.d
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 7 2007

SYNTHESIS AND STRUCTURE OF 2-ETHOXY- AND 2-AMINOMETHYLIDENE-...
953
(
1H, NH, J = 13.9 Hz); Z isomer: 1.39 t (3H,
(C=O, ester); 1637 (C=O, ketone); 1603, 1583, 1517
(C=C, δN–H); 1230–1147 (C–F). H NMR spectrum
1
OCH CH , J = 7.1 Hz), 2.35 s (3H, CH ), 4.35 q (2H,
2
3
3
OCH , J = 7.1 Hz), 6.60 t (HCF , J = 54.5), 8.62 d
(DMSO-d ), δ, ppm: 3.78 s (3H, OCH ), 7.00–7.02 m
2
2
6
3
(
1
3
1H, CH, J = 14.0 Hz), 11.29 br.d (1H, NH, J =
and 7.43–7.52 m (2H each, C H ); E isomer: 1.28 t
6 4
1
9
4.0 Hz). F NMR spectrum (CDCl ), δ , ppm:
(3H, OCH CH , J = 7.0 Hz), 4.19 q (2H, OCH , J =
3
F
2
3
2
4.15 d (HCF , E isomer, J = 54.5 Hz), 35.17 d (HCF ,
7.0 Hz), 6.99 t (1H, HCF , J = 53.0, 6.6 Hz), 8.44 d
2
2
2
Z isomer, J = 54.5 Hz). Found, %: C 59.21; H 5.36;
(1H, CH, J = 14.5 Hz), 12.10 br.d (1H, NH, J =
F 13.13; N 4.95. C H F NO . Calculated, %:
14.5 Hz); Z isomer: 1.15 t (3H, OCH CH , J = 6.0 Hz),
1
4
15
2
3
2
3
C 59.36; H 5.34; F 13.41; N 4.55.
4.27 q (2H, OCH , J = 6.0 Hz), 6.83 t (1H, HCF , J =
2 2
5
2.0 Hz), 8.26 br.d (1H, CH, J = 14.5 Hz), 10.97 br.d
Ethyl (2E)-4,4,4-trifluoro-2-(4-methylphenyl-
aminomethylidene)-3-oxobutanoate (VIIb). Yield
1
9
(
1H, NH, J = 14.5 Hz). F NMR spectrum (DMSO-d ),
6
–
1
δF, ppm: E isomer: 41.53 d.d (2F, 4-F, J = 14.8,
2
.11 g (70%) (b), mp 60–62°C. IR spectrum, ν, cm :
in mineral oil: 3225, 3456 (N–H); 1691 (C=O, ester);
633 (C=O, ketone); 1609, 1580 (C=C, δN–H); 1194–
144 (C–F); in CHCl : 1689 br (C=O, ester); 1637 br
7
4
.7 Hz), 25.35 d.t (2F, 5-F, J = 53.0, 7.7 Hz); Z isomer:
2.39 m (2F, 4-F), 24.11 d.m (2F, 5-F, J = 52.0 Hz).
1
1
Found, %: C 51.18; H 4.14; F 21.33; N 3.88.
C H F NO . Calculated, %: C 51.58; H 4.33;
F 21.76; N 4.01.
3
1
(C=O, ketone); 1604, 1577 (C=C, δN–H). H NMR
spectrum (CDCl ), δ, ppm: 7.08–7.15 m and 7.21–
15 15
4
4
3
7
.25 m (2H each, C H ); E isomer: 1.34 t (3H,
6 4
Ethyl (2E)-4,4,5,5,6,6,6-heptafluoro-2-(4-meth-
oxyphenylaminomethylidene)-3-oxohexanoate
(VIIIc). Yield 2.59 g (62%) (b), mp 60–62°C. IR spec-
trum, ν, cm : in mineral oil: 3206 (C–H); 1685 (C=O,
ester); 1653 (C=O, ketone); 1601, 1582, 1516 (C=C,
OCH CH , J = 7.2 Hz), 2.37 s (3H, CH ), 4.29 q (2H,
OCH , J = 7.2 Hz), 8.60 d (1H, CH, J = 14.1 Hz),
1
2
3
3
2
–
1
2.21 br.d (1H, NH, J = 14.1 Hz); Z isomer: 1.37 t
(
(
3H, OCH CH , J = 7.1 Hz), 2.36 s (3H, CH ), 4.33 q
2H, OCH , J = 7.1 Hz), 8.47 d (1H, CH, J = 14.1 Hz),
2
3
3
2
δN–H); 1274–1136 (C–F); in CHCl : 1680 br (C=O,
3
1
9
11.38 br.d (1H, NH, J = 14.1 Hz). F NMR spectrum
ester); 1631 br (C=O, ketone); 1604, 1579 (C=C,
1
(
(
CDCl ), δ , ppm: 89.07 s (CF , E isomer), 89.99 s
CF , Z isomer). Found, %: C 55.93; H 4.73; F 18.93;
3
F
3
δN–H). H NMR spectrum (CDCl ), δ, ppm: E isomer:
3
3
1.33 t (3H, OCH CH , J = 7.2 Hz), 3.83 s (3H, OCH ),
2
3
3
N 4.67. C H F NO . Calculated, %: C 55.82; H 4.68;
F 18.92; N 4.65.
14
14
3
3
4.29 q (2H, OCH , J = 7.2 Hz), 6.95 d.m (2H, C H ,
2
6
4
J = 8.9 Hz), 7.16 d.m (2H, C H , J = 8.9 Hz), 8.45 d
6
4
Ethyl (2E)-4,4,4-trifluoro-2-(4-methoxyphenyl-
aminomethylidene)-3-oxobutanoate (VIIIa). Yield
(1H, CH, J = 14.0 Hz), 12.18 br.d (1H, NH, J =
14.0 Hz); Z isomer: 1.35 t (3H, OCH CH , J = 7.1 Hz),
3.82 s (3H, OCH ), 4.32 q (2H, OCH , J = 7.1 Hz),
6.94 d.m (2H, C , J = 8.9 Hz), 7.13 d.m (2H, C
2
3
1
.46 g (46%) (b), oily substance. IR spectrum (film), ν,
3
2
–1
cm : 3226 (N–H); 2984 (C–H); 1724 (C=O, ester);
6
H
4
H ,
6 4
1
1
701 (C=O); 1634, 1607, 1581, 1516 (C=C, δN–H);
J = 8.9 Hz), 8.30 d (1H, CH, J = 14.2 Hz), 11.27 br.d
(1H, NH, J = 14.2 Hz). F NMR spectrum (CDCl3),
1
19
275–1158 (C–F). H NMR spectrum (CDCl ), δ,
3
ppm: 6.93–6.97 m and 7.13–7.20 m (2H each, C H );
δF, ppm: E isomer: 38.26 m (2F, 5-F), 48.61 q.m (2F,
4-F, J = 9.9 Hz), 81.56 t (3F, 6-F, J = 9.9 Hz);
Z isomer: 37.58 m (2F, 5-F), 49.22 q.m (2F, 4-F, J =
9.6 Hz), 81.68 t (3F, 6-F, J = 9.6 Hz). Found, %:
C 46.10; H 3.40; F 31.61; N 3.25. C H F NO . Cal-
6
4
E isomer: 1.34 t (3H, OCH CH , J = 7.0 Hz), 3.83 s
2
3
(
(
3H, OCH ), 4.29 q (2H, OCH , J = 7.0 Hz), 8.54 d
3 2
1H, CH, J = 14.1 Hz), 12.27 br.d (1H, NH, J =
4.1 Hz); Z isomer: 1.37 t (3H, OCH CH , J = 7.0 Hz),
1
3
8
1
8
2
3
16 14
7
4
.82 s (3H, OCH ), 4.32 q (2H, OCH , J = 7.0 Hz),
culated, %: C 46.05; H 3.38; F 31.87; N 3.36.
3
2
.41 d (1H, CH, J = 14.3 Hz), 11.39 br.d (1H, NH, J =
Ethyl (2E)-4,4,4-trifluoro-3-oxo-2-(pyridin-2-yl-
aminomethylidene)butanoate (IXa). Yield 1.61 g
1
9
4.3 Hz). F NMR spectrum (CDCl ), δ , ppm:
3
F
9.14 s (CF , E isomer), 90.04 s (CF , Z isomer).
3
3
(
56%) (b), mp 72–73°C. IR spectrum (mineral oil), ν,
Found, %: C 52.85; H 4.32; F 17.68; N 4.35.
C H F NO . Calculated, %: C 53.00; H 4.45;
–1
cm : 3251 (N–H); 1702 (C=O, ester); 1633 (C=O,
1
4
14
3
4
ketone); 1607, 1591, 1561 (C=C, C=N, δN–H); 1198–
F 17.96; N 4.41.
1
1
113 (C–F). H NMR spectrum (CDCl ), δ, ppm:
3
Ethyl (2E)-4,4,5,5-tetrafluoro-2-(4-methoxy-
phenylaminomethylidene)-3-oxopentanoate (VIIIb).
Yield 2.06 g (59%) (b), 1.50 g (43%) (c), mp 89–91°C.
E isomer: 1.36 t (3H, OCH CH , J = 7.0 Hz), 4.32 q
2
3
(2H, OCH , J = 7.0 Hz), 7.08 br.d (1H, 3′-H, J
=
2
3′,4′
8.0, J3′,5′ = 0.8 Hz), 7.19 d.d.d (1H, 5′-H, J5′,4′ = 7.4,
J5′,6′ = 4.8, J5′,3′ = 0.8 Hz), 7.76 d.d.d (1H, 4′-H, J4′,3′
–
1
IR spectrum (mineral oil), ν, cm : 2986 (C–H); 1700
=
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 7 2007

9
8
54
PRYADEINA et al.
.0, J4′, 5′ = 7.4, J4′, 6′ = 1.2 Hz), 8.44 d.d (1H, 6′-H,
7.2 Hz), 4.33 q (2H, OCH , J = 7.2 Hz), 7.11 t (1H,
2
J6′, 5′ = 4.8, J6′, 4′ = 1.8 Hz), 9.36 d (1H, CH, J =
5′-H, J = 4.9 Hz), 8.64 d (2H, 4′-H, 6′-H, J = 4.9 Hz),
9.29 d (1H, CH, J = 13.5 Hz), 11.68 d (1H, NH, J =
13.5 Hz); Z isomer: 1.38 t (3H, OCH CH , J = 7.2 Hz),
13.3 Hz), 12.08 br.d (1H, NH, J = 13.3 Hz); Z isomer:
1
.38 t (3H, OCH CH , J = 7.0 Hz), 4.35 q (2H, OCH ,
2
3
2
2
3
J = 7.0 Hz), 6.96 br.d (1H, 3′-H, J3′, 4′ = 8.2, J3′, 5′
=
4.36 q (2H, OCH , J = 7.2 Hz), 7.15 t (1H, 5′-H, J =
2
0
.8 Hz), 7.14 d.d.d (1H, 5′-H, J5′,4′ = 7.4, J5′,6′ = 4.8,
J5′,3′ = 0.8 Hz), 7.73 d.d.d (1H, 4′-H, J4′,3′ = 8.0, J4′,5′
.4, J4′, 6′ = 1.2 Hz), 8.41 d.d (1H, 6′-H, J6′, 5′ = 4.8,
J6′, 4′ = 1.2 Hz), 9.23 d (1H, CH, J = 13.1 Hz),
4.9 Hz), 8.61 d (2H, 4′-H, 6′-H, J = 4.9 Hz), 9.14 d
(1H, CH, J = 13.1 Hz), 11.21 d (1H, NH, J = 13.1 Hz).
=
1
9
7
F NMR spectrum (CDCl ), δ , ppm: 88.53 s (CF ,
3 F 3
E isomer), 89.94 s (CF , Z isomer). Found, %: C 45.66;
3
1
9
11.41 br.d (1H, NH, J = 13.1 Hz). F NMR spectrum
H 3.28; F 19.69; N 14.64. C H F N O . Calculated,
11
10
3
3
3
(
(
CDCl ), δ , ppm: 88.79 s (CF , E isomer), 90.15 s
%: C 45.68; H 3.49; F 19.71; N 14.53.
3
F
3
CF , Z isomer). Found, %: C 49.99; H 3.79; F 19.75;
3
Ethyl (2Z)-4,4,4-trifluoro-2-(morpholinomethyli-
dene)-3-oxobutanoate (XIa). Yield 2.08 g (74%) (b),
N 9.63. C H F N O . Calculated, %: C 50.01;
H 3.85; F 19.77; N 9.72.
1
2
11
3
2
3
–1
mp 65–67°C. IR spectrum, ν, cm : in mineral oil:
Ethyl (2E)-4,4,5,5,6,6,6-heptafluoro-3-oxo-2-
pyridin-2-ylaminomethylidene)hexanoate (IXb).
3005 (C–H), 1699 (C=O, ester), 1644 (C=O, ketone),
1575 (C=C), 1205–1114 (C–F); in CHCl : 1701 (C=O,
ester), 1665 (C=O, ketone), 1570 (C=C). H NMR
(
3
1
Yield 2.39 g (62%) (b), mp 65–67°C. IR spectrum
–1
(
(
1
film), ν, cm : 3271 (N–H); 1668 (C=O, ester); 1668
spectrum (CDCl ), δ, ppm: 1.31 t (3H, OCH CH , J =
3
2
3
C=O, ketone); 1608, 1562, 1476 (C=C, C=N, δN–H);
7
.2 Hz), 3.48 m and 3.81 m (4H each, CH CH ), 4.22 q
2 2
1
230–1120 (C–F). H NMR spectrum (CDCl ), δ,
3
(2H, OCH CH , J = 7.2 Hz), 7.64 s (1H, CH).
2
3
19
ppm: E isomer: 1.35 t (3H, OCH CH , J = 7.2 Hz),
4
2
3
F NMR spectrum (CDCl ): δ 89.62 ppm, s (CF ).
3 F 3
.31 q (2H, OCH , J = 7.2 Hz), 6.99 br.d (1H, 3′-H,
2
Found, %: C 46.92; H 4.98; F 20.16; N 4.89.
C H F NO . Calculated, %: C 46.98; H 5.02;
J3′,4′ = 8.0, J3′,5′ = 0.8 Hz), 7.13 d.d.d (1H, 5′-H, J5′,4′
.0, J5′,6′ = 4.8, J5′,3′ = 0.7 Hz), 7.76 d.d.d (1H, 4′-H,
J4′,3′ = 8.0, J4′,5′ = 7.0, J4′,6′ = 1.7 Hz), 8.44 d.d (1H,
=
1
1
14
3
4
7
F 20.27; N 4.98.
Ethyl (2Z)-4,4,5,5-tetrafluoro-2-(morpholino-
methylidene)-3-oxopentanoate (XIb). Yield 1.96 g
6
1
1
′-H, J6′,5′ = 4.8, J6′,4′ = 1.7 Hz), 9.28 d (1H, CH, J =
3.2 Hz), 11.95 d (1H, NH, J = 13.2 Hz); Z isomer:
.36 t (3H, OCH CH , J = 7.2 Hz), 4.34 q (2H, OCH ,
–
1
(
70%) (b), mp 50–52°C. IR spectrum, ν, cm (mineral
2
3
2
oil): 3017 (C–H), 1691 (C=O, ester), 1653 (C=O),
J = 7.2 Hz), 6.94 br.d (1H, 3′-H, J3′, 4′ = 8.0, J3′, 5′
=
1
1
571 (C=C), 1214–1075 (C–F). H NMR spectrum
0
.8 Hz), 7.12 d.d.d (1H, 5′-H, J5′,4′ = 7.1, J5′,6′ = 4.8,
J5′,3′ = 0.7 Hz), 7.72 d.d.d (1H, 4′-H, J4′,3′ = 8.0, J4′,5′
.1, J4′, 6′ = 1.7 Hz), 8.40 d.d (1H, 6′-H, J6′, 5′ = 4.8,
J6′,4′ = 1.4 Hz), 9.14 d (1H, CH, J = 13.0 Hz), 11.28 d
(
CDCl ), δ, ppm: 1.31 t (3H, OCH CH , J = 7.2 Hz),
3
2
3
=
3
.79 m and 3.45 m (4H each, CH CH ), 4.23 q (2H,
2 2
7
OCH CH , J = 7.2 Hz), 6.33 t.t (1H, HCF , J = 53.3,
2
3
2
19
1
9
5
.9 Hz), 7.58 s (1H, CH). F NMR spectrum (CDCl ),
(
1H, NH, J = 13.0 Hz). F NMR spectrum (CDCl3),
δF, ppm: E isomer: 38.17 m (2F, 5-F), 48.25 q.m (2F,
-F, J = 9.8 Hz), 81.52 t (3F, 6-F, J = 9.8 Hz);
Z isomer: 37.24 m (2F, 5-F), 49.03 q.m (2F, 4-F, J =
.5 Hz), 81.61 t (3F, 6-F, J = 9.5 Hz). Found, %:
C 43.43; H 2.67; F 34.10; N 7.18. C H F N O . Cal-
3
δF, ppm: 22.23 d.m (2F, 5-F, J = 53.3 Hz), 40.26 m (2F,
4-F). Found, %: C 51.09; H 5.32; F 26.92; N 4.74.
4
C H F NO . Calculated, %: C 51.25; H 5.38;
12 15
4
4
F 27.02; N 4.98.
9
1
4
10
7
2
3
Ethyl (2Z)-4,4,5,5,6,6,6-heptafluoro-2-(morpho-
linomethylidene)-3-oxohexanoate (XIc). Yield 2.44 g
(64%) (b), mp 65–67°C. IR spectrum (mineral oil), ν,
culated, %: C 43.42; H 2.60; F 34.34; N 7.23.
Ethyl (2E)-4,4,4-trifluoro-3-oxo-2-(pyrimidin-2-
ylaminomethylidene)butanoate (X). A mixture of
2
–
1
cm : 3004 (C–H); 1724 (C=O, ester); 1703 (C=O);
1
.40 g (0.01 mol) of ester IIa and 0.95 g (0.01 mol) of
1647, 1633, 1555 (C=C); 1256–1117 (C–F). H NMR
pyrimidin-2-amine in 10 ml of 1,4-dioxane was heated
for 48 h under reflux. The mixture was evaporated, and
the residue was recrystallized from hexane. Yield
spectrum (CDCl
7.2 Hz), 3.46 m and 3.80 m (4H each, CH
(2H, OCH CH , J = 7.2 Hz), 7.56 s (1H, CH).
F NMR spectrum (CDCl ), δ , ppm: 37.27 m (2F,
3
), δ, ppm: 1.29 t (3H, OCH
2
CH
3
, J =
CH
), 4.23 q
2
2
2
3
1
9
1
.30 g (45%), mp 108–110°C. IR spectrum (mineral
3
F
–1
oil), ν, cm : 3278 (N–H); 3104 (C–H); 1716 (CO,
5-F), 48.18 m (2F, 4-F, J = 9.8 Hz), 81.42 t (3F, 6-F,
J = 9.8 Hz). Found, %: C 40.90; H 3.68; F 34.80;
N 3.69. C H F NO . Calculated, %: C 40.96; H 3.70;
ester); 1657 (C=O, ketone); 1596, 1574, 1553 (C=C,
1
C=N, δN–H); 1220–1113 (C–F). H NMR spectrum
1
3
14
7
4
(
CDCl ), δ, ppm: E isomer: 1.37 t (3H, OCH CH , J =
F 34.88; N 3.67.
3
2
3
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 7 2007

SYNTHESIS AND STRUCTURE OF 2-ETHOXY- AND 2-AMINOMETHYLIDENE-...
955
Ethyl (2Z)-4,4,4-trifluoro-3-oxo-2-(pyrrolidin-1-
ylmethylidene)butanoate (XII). Yield 1.54 g (58%)
pal, J., and Thomas, D., Org. Prep. Proced. Int., 1982,
vol. 15, p. 327; Chem. Abstr., 1982, vol. 97, no. 181887.
3. Jones, R.G., J. Am. Chem. Soc., 1951, vol. 73, p. 3684.
–
1
(
b), oily substance. IR spectrum (film), ν, cm : 3010
(
1
C–H), 1706 (C=O, ester), 1654 (C=O), 1574 (C=C),
4. Danion-Bougot, R. and Carrie, R., C.R. Acad. Sci., Ser.
C, 1967, vol. 264, p. 457; Currie, D.J., Lough, C.E.,
McClusky, F.K., and Holmes, H.L., Can. J. Chem.,
1
200–1150 (C–F). H NMR spectrum (CDCl ), δ,
3
ppm: 1.31 t (3H, OCH CH , J = 7.2 Hz), 2.03 t (2H,
CH , J = 6.7 Hz), 3.14 m (2H, CH ), 3.29 t.t (2H, CH ,
J = 6.7, 7.2 Hz), 3.76 t (2H, CH , J = 7.2 Hz), 4.22 q
(
spectrum (CDCl ): δ 89.55 ppm, s (CF ). Found, %:
C 49.62; H 5.65; F 21.30; N 5.53. C H F NO . Cal-
culated, %: C 49.81; H 5.32; F 21.49; N 5.28.
2
3
1
969, vol. 47, p. 3147.
2
2
2
5
6
7
. Pryadeina, M.V., Kuzueva, O.G., Burgart, Ya.V., and Sa-
loutin, V.I., Russ. J. Org. Chem., 2002, vol. 38, p. 224.
. Potapov, V.M., Stereokhimiya (Stereochemistry),
Moscow: Khimiya, 1988, p. 263.
. Oki, M., Applications of Dynamic NMR Spectroscopy to
Organic Chemistry, Deerfield Beach: VCH, 1985,
pp. 77, 112.
2
19
2H, OCH , J = 7.2 Hz), 7.89 s (1H, CH). F NMR
2
3
F
3
13
14
7
4
This study was performed under financial support
by the Russian Foundation for Basic Research (project
nos. 05-03-32384, 06-03-08141-ofia), by the Program
for State Support of Leading Scientific Schools
8
. Ionin, B.I., Ershov, B.A., and Kol’tsov, A.I., YaMR-
spektroskopiya v organicheskoi khimii (NMR Spectros-
copy in Organic Chemistry), Leningrad: Khimiya, 1983,
p. 46; Levy, G.C., Lichter, R.L., and Nelson, G.L.,
Carbon-13 Nuclear Magnetic Resonance Spectroscopy,
New York: Wiley, 1980, p. 143.
(
project no. 9178.2006.3), and by the Foundation for
Support of Russian Science.
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Chupakhin, O.N., Russ. J. Org. Chem., 2007, vol. 43,
p. 380.
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2
. Pashkevich, V.M. and Saloutin, V.I., Usp. Khim., 1985,
vol. 54, p. 1997.
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 7 2007