Synthesis and Wittig Reaction of Formylated (Trifluoromethylfuryl)methanephosphonates

Article abstract of DOI:10.1134/S1070363218020093

Methods of synthesis of 4-functionalyzed (5-trifluoromethylfur-2-yl)methanephosphonates and (5-methyl-2-trifluoromethylfur-3-yl)methanephosphonate are developed. Their formylation with ethyl formate in the presence of sodium foil is studied. Spectral char

Full text of DOI:10.1134/S1070363218020093

ISSN 1070-3632, Russian Journal of General Chemistry, 2018, Vol. 88, No. 2, pp. 241–250. © Pleiades Publishing, Ltd., 2018.
Original Russian Text © E.P. Doronina, L.M. Pevzner, V.A. Polukeev, M.L. Petrov, 2018, published in Zhurnal Obshchei Khimii, 2018, Vol. 88, No. 2,
pp. 262–272.
Synthesis and Wittig Reaction of Formylated
(Trifluoromethylfuryl)methanephosphonates
E. P. Doroninaa, L. M. Pevznera*, V. A. Polukeevb, and M. L. Petrova
a St. Petersburg Institute of Technology (Technical University), Moskovskii pr. 26, St. Petersburg, 190013 Russia
*e-mail: pevzner_lm@list.ru
b Institute of Experimental Medicine, St. Petersburg, Russia
Received June 6, 2017
Abstract—Methods of synthesis of 4-functionalyzed (5-trifluoromethylfur-2-yl)methanephosphonates and
(5-methyl-2-trifluoromethylfur-3-yl)methanephosphonate are developed. Their formylation with ethyl formate
in the presence of sodium foil is studied. Spectral characteristics of tautomers of obtained derivatives of
phosphonoacetic aldehyde are evaluated. It is shown that interaction of obtained formyl derivatives with
ethoxycarbonylmethylenetriphenylphosphorane regardless of the structure of the furan fragment leads to
4-furylsubstituted alkyl 4-(diethoxyphosphoryl)but-3-enoate, the abnormal product of Wittig reaction.
Keywords: trifluoromethylfuranes, methanephosphonates, formylation, tautomerism, Wittig reaction
DOI: 10.1134/S1070363218020093
Recently we have found that diethyl (5-trifluoro-
methylfur-2-yl)methanephosphonate prepared from the
corresponding bromomethylfuran via the Arbuzov
reaction can be formylated at the active methylene
group to give trifluoromethylfuryl derivative of
phosphonoacetic aldehyde. This compound is
completely enolized. Despite of this fact the above-
mentioned compound reacts with ethoxycarbonyl-
methylenetriphenylphosphorane to give the abnormal
product of Wittig reaction, ethyl 4-(5-trifluoro-
methylfur-2-yl)-4-(diethoxyphosphoryl)but-3-enoate
[1, 2]. This reaction was thoroughly studied by an
example of ethoxycarbonylfuryl and cyanofuryl deri-
vatives of (diethoxyphosphoryl)acetic aldehyde [3]. It
occurred that in all cases the abnormal product was
preferable, but if the electron-acceptor group and
phosphorus-containing substituent occupy neighboring
positions of the furan ring the formation of usual
product of the Wittig reaction, 4-furylsubstituted
4-(diethoxyphosphoryl)but-2-enoate was also observed.
In the last case trifluoromethyl group was adjacent to
the active methylene one. Evaluation of its effect on
the Claisen formylation and the subsequent Wittig
reaction presented special interest.
First step in solving these problems was the
synthesis of alkyl (5-trifluoromethylfur-2-yl)methane-
phosphonates containing ethoxycarbonyl or cyano
group in the furan ring. Evidently their presence would
increase CH-acidity of the furan-CH2P fragment and
facilitate its participation in ester condensation.
Ethyl 2-trifluoromethyl-5-methyl-3-furoate 1 was
chosen as the starting substance. By bromination with
NBS in the presence of AIBN it was converted to the
known bromide 2 [4]. Phosphorylation of the latter
with triethyl phosphite via the Arbuzov reaction gave
phosphonate 3 in 63% yield (Scheme 1). In NMR
spectra of this compound the signal of phosphorus
nucleus was observed at 20.76 ppm, the doublet of
protons of P–CH2-furan fragment was located at
3.20 ppm (JPH = 20.8 Hz), and the signal of the cor-
responding carbon atom, at 20.42 ppm (1JPC = 142.8 Hz).
The signal of fluorine nuclei was registered at –61.18 ppm.
In this work we have continued studies of this
reaction range with the participation of derivatives of
diethyl (5-trifluoromethylfur-2-yl)methanephosphonate
containing additional electron-acceptor substituent that
is the ester or nitrile group in the furan ring, and also
diethyl (2-trifluoromethylfur-3-yl)methanephosphonate.
We presumed that diethyl (4-cyano-5-trifluoro-
methylfur-2-yl)methanephosphonate 4 must be the
most available via the sequence of transformations
241

242
DORONINA et al.
Scheme 1.
EtOOC
F3C
EtOOC
F3C
EtOOC
F3C
NBS
P(OEt)3
Br
PO(OEt)2
AIBN
O
O
O
1
2
3
Scheme 2.
H2NOC
NC
NC
ClOC
NBS
PCl5
NH4OH
Br
O
6
O
7
AIBN
O
5
O
F3C
F3C
F3C
F3C
Scheme 3.
EtOOC
CF3
HOOC
ClOC
CF3
KOH_EtOH
HCl_EtOH
CH3COONa
CH3COOH
SOCl2
DMF
OCOCH3
2
CH2OH
CH2Cl
O
O
O
CF3
8
9
10
including the dehydration of amide 6 to nitrile 7, the
bromination of the latter at methyl group and
prosphorylation of bromide 8 using the Arbuzov
reaction (Scheme 2).
[5] acetate 8 was obtained. Its hydrolysis with ethanol
solution of potassium hydroxide at room temperature
gave hydroxyl acid 9 in a 94% yield. By boiling this
acid with thionyl chloride in benzene in the presence of
DMF the chloride of 2-trifluoromethyl-5-chloromethyl-3-
furoic acid 10 was synthesized in a 48% yield. The
Starting acid chloride 5 was prepared according to a
described protocol [4] from ester 1. Treating its cold
benzene solution with 25% ammonia gave the cor-
1
singlet of chloromethyl group protons in its H NMR
1
spectrum was located at 4.61 ppm. The signal of the
corresponding carbon atom appeared at 35.45 ppm,
and of the carbonyl carbon atom, at 158.85 ppm. The
signal of fluorine nuclei was found at –62.79 ppm.
responding amide 6 in 68% yield. In the H NMR
spectrum of this substance two broad signals at 7.48
and 7.81 ppm were present. That proves the formation
of a primary amide group. Amide 6 was converted to
nitrile 7 by treating with phosphorus pentachloride by
boiling in tetrachloromethane for 2.5 h. The target
product was isolated by a vacuum distillation in a 62%
yield. The formation of a nitrile group was confirmed
by the appearance of a characteristic signal of carbon
atom at 110.44 ppm (CN), the disappearance of the
carbonyl group signal at 162.12 ppm and by the
upfield shift of the signal of C3 carbon atom of the
furan ring from 125.68 ppm in the starting amide to
99.67 ppm in the reaction product. All attempts to
brominate nitrile 7 with NBS failed. Regardless of
used amount of AIBN only starting substance was
isolated from the reaction mixture.
Treating benzene solution of acid chloride 10 with
ammonia at 4–5°C lead to amide 11 in 48% yield
(Scheme 4). Under these conditions the chloromethyl
group did not take part in the reaction. Dehydration of
amide 11 to nitrile was carried out by treating with
phosphorus pentachloride in phosphorus oxychloride-
carbon tetrachloride mixture. This system was found to
be much more efficient than phosphorus pentachloride
in tetrachloromethane or benzene. Instead of usually
observed 50–60% yield nitrile 12 was obtained in 92%
yield. Its isolation was also simple. As a rule, dehyd-
rochlorination of the majority of imidoyl chloride
formed in the reaction of phosphorus pentachloride
with amide proceeds while distillation at about 100°C.
In the case under consideration this process takes place
directly in the reaction mixture. It is proved by more
intense evolution of hydrogen chloride and absence of
Because of that another pathway beginning from
transformation of methyl group in the furan ring was
developed (Scheme 3). By treating bromide 2 with
sodium acetate in acetic acid according to the protocol
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SYNTHESIS AND WITTIG REACTION
243
Scheme 4.
NC
H2NOC
NH4OH
POCl3 + PCl5
10
O
O
CH2Cl
CH2Cl
CF3
CF3
11
12
NC
NC
P(OEt)3
NaI
O
O
CH2PO(OEt)2
CH2I
CF3
CF3
13
14
Scheme 5.
HOCH2
ClCH2
(EtO)2OPCH2
F3C
SOCl2
C5H5N
NaPO(OEt)2
LiAlH4
1
O
16
O
17
O
15
F3C
F3C
solid phase after removing the solvent. Evidently,
phosphorus oxychloride also reacts with amide and
forming phosphoric acid dichloride catalyzes dehydro-
chlorination of imidoyl chloride. Simultaneously
reaction of phosphorus pentachloride with phosphoric
acid dichloride takes place, its only product being
phosphorus oxychloride. Signal of the nitrile group
carbon atom in the 13C NMR spectrum of compound
12 was observed at 109.64 ppm.
phosphorus atom in this compound was observed at
19.71 ppm, the doublet of phosphonomethyl group
protons was found at 3.29 ppm (JPH = 21.2 Hz), and
the signal of the corresponding carbon atom, at
26.66 ppm (1JPC = 142.9 Hz).
The synthesis of diethyl (2-trifluoromethyl-5-me-
thylfur-3-yl)methanephosphonate 15 began by reduc-
tion of ester 1 to alcohol 16 with lithium aluminum
hydride (Scheme 5). The target product was isolated
by vacuum distillation in a 70% yield. The signal of
hydroxymethyl group protons in this substance was
observed at 4.59 ppm and of the corresponding carbon
atom, at 55.10 ppm. 3-Chloromethylfuran 17 was
prepared in a 48% yield by treating ethyl acetate
solution of alcohol 16 and pyridine with thionyl
chloride. The formation of chloromethyl fragment was
confirmed by the signal of chloromethyl group protons
at 4.51 ppm and of the corresponding carbon atom, at
34.89 ppm. Phosphorylation of chloride 17 was carried
out under conditions of the Michaelis–Becker reaction
with sodium diethyl phosphite in benzene at 80°C for
16 h. Phosphonate 15 was isolated by vacuum distilla-
tion in a 69% yield.
Chloromethyl derivative 12 had the desired struc-
ture, but such compounds enter the Arbuzov reaction
only at 160–170°C what may provoke their decom-
position. Therefore we tried to prepare much more
active iodomethyl derivative 13 by means of the
Finkelstein reaction. The substitution of chlorine for
iodine was carried out at room temperature in the dark
using saturated acetone solution of sodium iodide
dihydrate. The target product 13 was obtained in 57%
yield. The signal of iodomethyl group protons was
observed at 4.38 ppm, that of the corresponding carbon
atom, at –11.88 ppm, and of the nitrile group carbon
atom, at 109.72 ppm. As compared to another known
iodomethylfurans compound 13 is relatively stable
towards light.
Hence, two new phosphonates 3 and 14 were
synthesized. In these substances phosphonomethyl
group is located in the position 2 of the furan ring. It is
exposed to combined acidifying action of trifluoro-
methyl and ethoxycarbonyl or cyano groups. New
phosphonate 15 contained phosphonomethyl group in
Phosphorylation of amide 13 was carried out by
treating with triethyl phosphite under heating and
distillation of evolving ethyl iodide from the reaction
mixture (Scheme 4). Phosphonate 14 was isolated by a
vacuum distillation in a 51% yield. The signal of the
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244
DORONINA et al.
Scheme 6.
EtOOC
F3C
EtOOC
F3C
O
O
(1) EtOCHO, Na
(2) HCl
P(OEt)2
P(OEt)2
3
O
O
OH
H
18a
H
HO
18b
Scheme 7.
NC
NC
O
O
(1) Na + EtOCHO
(2) HCl
P(OEt)2
P(OEt)2
14
O
O
F3C
F3C
OH
H
H
19a
HO
19b
the position 3 of the furan ring which was acidified
only by the action of 2-trifluoromethyl group. Next
step of our work was the formylation of these
compounds under the conditions of Claisen reaction.
(18a) and at 92.02 ppm (1JPC = 202.8 Hz) (18b).
Signals of carbon atom bound with oxygen are found
at 160.83 and 161.03 ppm (2JPC = 20.6 Hz) respec-
tively [6–8].
The formylation of phosphonate 3 was carried out
according to protocol [1] in benzene at phosphonate :
sodium : ethyl formate molar ratio 1.0 : 1.2 : 2.0
(Scheme 6). In the course of the reaction the
dissolution of sodium and insignificant heat evolution
in the course of ~4 h was observed. Sodium enolate
was not isolated from the reaction mixture. After
extraction of reaction products with water and
acidifying of extract with hydrochloric acid to pH 2–3
formyl derivative 18 was isolated in a 48% yield.
The formylation of phosphonate 14 was carried out
analogously. Formyl derivative 19 was isolated in a
39% yield (Scheme 7). In 31P NMR spectrum of
obtained compound two signals at 17.37 and
19.06 ppm with the intensity ratio 0.2 : 1.0 are
presented. In 19F NMR spectrum the signals of tri-
fluoromethyl groups with the same ratio of intensities
are located at –63.56 and –63.48 ppm. In the 1H NMR
spectrum of this preparation two doublets at 7. 79 ppm
(JPH = 10.4 Hz) and 7.92 ppm (JPH = 39.2 Hz) with the
intensity ratio 0.2 : 1.0 and the broadened signal at
11.75 ppm are found. Hence, compound 19 is also a
mixture of Z-enol 19a and E-enol 19b [6–8]. Similarly
to the previous case Z-enol is the main product. In the
13C NMR spectrum signals of carbon atoms directly
In the 31P NMR spectrum of the obtained prepara-
tion two signals at 18.42 and 19.88 ppm with the
intensity ratio 0.2 : 1.0 were observed. 19F NMR spec-
trum contained two signals at –61.36 and –61.33 ppm
1
with the same ratio of intensities. In the H NMR
bound with phosphorus are located at 91.09 ppm (1JPC
=
spectrum two doublets at 7.73 (JPH = 10.4 Hz) and
7.87 ppm (JPH = 38.4 Hz) with the intensity ratio
0.2 : 1.0 and the broadened signal at 11.58 ppm are
present. These data show that formyl derivative 18 is
completely enolyzed in solution. It exists as a mixture
of isomers with Z- (18a) and E-location (18b) of di-
ethoxyphosphoryl and hydroxy groups, Z-isomer being
the main form. Signals of H3 proton of the furan ring in
these compounds also differ. They appear at 6.54 ppm
for Z-enol and at 7.03 ppm for E-enol. In the 13C NMR
spectrum signals of carbon atom directly bound with
phosphorus are located at 91.09 ppm (1JPC = 180.5 Hz)
180.5 Hz) (19a) and 91.75 ppm (1JPC = 179.1 Hz)
(19b). Signals of carbon atoms bound with oxygen are
registered at 164.87 pm (2JPC = 1.1 Hz) and
162.30 ppm (2JPC = 20.7 Hz) respectively [7]. Nucleus
of the carbon atom of the nitrile group resonates at
110.18 ppm.
By the formylation of phosphonate 15 according to
the above-described protocol formyl derivative 20
(Scheme 8) was obtained. In 31P NMR spectrum of this
preparation three signals at 16.19, 22.04, and
21.44 ppm with the intensity ratio 0.3 : 0.7 : 1.0 were
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SYNTHESIS AND WITTIG REACTION
245
Scheme 8.
O
O
O
P(OEt)2
P(OEt)2
P(OEt)2
HO
H
O
(1) Na + EtOCHO
(2) HCl
OH
F3C
H
F3C
15
O
O
O
F3C
20b
20a
20c
observed. In 19F NMR spectrum three signals at
–61.27, –60.11, and –63.43 ppm with the same intensity
ratio were present. In the H NMR spectrum a doublet
coupling with fluorine. Quartet of =CH–O fragment is
located at 163.77 ppm (5JFC = 2.4 Hz). This signal is
not split from phosphorus what is characteristic of
Z-enol forms [7, 8]. Signal of H4 proton of the furan
ring of Z-enol 20b is located at 6.50 ppm.
1
at 4.53 ppm (JPH = 28.0 Hz) and a singlet of the same
intensity at 9.76 ppm were registered. In the 13C NMR
spectrum signals of the corresponding carbon atoms
were located at 50.12 ppm (1JPC = 129.6 Hz) and
191.75 ppm (2JPC = 4.3 Hz). These spectral data show
that not only E- and Z-enols, but also the aldehyde
form containing PCH–CHO fragment is present [7].
The signal of the furan ring proton corresponding by
intensity to the aldehyde proton signal was located at
6.40 ppm, and of methyl group, at 2.37 ppm. The
described set of signals characterizes aldehyde 20a
which is present in the mixture in the smallest amount.
More intense set of proton signals includes a singlet at
Hence, the structure of trifluoromethylfuryl deri-
vatives of phosphonoacetic aldehyde strongly depends
on the structure of substituents in the furan ring. If the
substituents in the furan ring are remote from the
phosphorus-containing fragment as in 5-trifluoro-
methylfuryl derivative [1] or in 4,5-disubstituted phos-
phonates 18, 19, these substances are completely
enolized in chloroform. In all the cases Z-isomer
prevails. CH-acidity of 2-trifluoromethyl-5-methylfur-
3-yl derivative is evidently lower. Therefore in the
equilibrium mixture in chloroform a significant
amount of aldehyde form appears there though enol
ones still prevail. Probably because of sterical factors
E-isomer becomes the main one, but its prevalence is
not large.
6.01 ppm (H4-furan) and a doublet at 7.61 ppm (JPH
=
10.0 Hz). These signals can be attributed to E-enol
20b. Hydroxyl proton of this enol form evidently
easily exchanges with deuterium because the residual
1
signal of chloroform in the H NMR spectrum of
Formyl derivatives 18–20 were involved in Wittig
reaction with ethoxycarbonylmethylenetriphenylphos-
phorane analogously to [3]. The reaction was carried
out in benzene at boiling at phosphonate : phosphorane
molar ratio = 1 : 1.2 (Scheme 9). The reaction progress
was monitored by means of 31P NMR spectroscopy.
phosphonate 20 is much more intense, than in all the
other cases. Signal of carbon atom directly bound with
phosphorus belonging to 20b form was located at
89.90 ppm (1JPC = 181.4 Hz). Doublet of =CH–O
carbon atom of this form was observed at 159.55 ppm
with the characteristic coupling constant 25.9 Hz [7].
All components of the signal are broadened due to the
coupling with fluorine nuclei. Third set of signals of
protons with relative intensity 0.7 included broad
doublet at 11.17 ppm and a doublet of doublets at
7.24 ppm. A large coupling constant of the last signal
(40.0 Hz) is characteristic of the olefin proton trans-
located to phosphorus which belongs to Z-enol 20b.
This proton interacts with the exchange proton of enol
hydroxyl group. As the signals are broadened, the
convergence of the coupling constant values is not
strict its average meaning being 12.0 Hz. In the 13C
NMR spectrum the signal of the carbon atom directly
In the reaction of compound 18 the abnormal
product of Wittig reaction, ethyl E-4-(4-ethoxycar-
bonyl-5-trifluoromethylfur-2-yl)-4-(diethoxyphosphoryl)-
but-3-enoate is formed in 80% yield (Scheme 9). In the
1H NMR spectrum of this substance two doublets of
Scheme 9.
EtOOC
COOEt
Ph3P=CH__COOEt
18
O
F3C
bound with phosphorus appears at 91.34 ppm (1JPC
205.7 Hz). Its components are broadened because of
=
(EtO)2OP
21
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246
DORONINA et al.
doublets at 3.60 (JHH = 7.0, JPH = 3.2 Hz) and
3.89 ppm (JHH = 7.0, JPH = 3.2 Hz) with the intensity
ratio 1 : 0.4 and total intensity 2H were present. A
doublet of triplets with total intensity corresponding to
1H was located at 7.13 ppm (JHH = 7.0, JPH = 23.2 Hz).
These data show the formation of olefin fragment with
phosphorus trans-located with respect to ethoxycar-
bonylmethylene group [8]. The compound probably
exists as a mixture of two spectroscopically different
conformers. It is confirmed also by the presence of two
phosphorus signals at 11.87 and 14.03 ppm (0.4 : 1.0)
in 31P NMR spectrum and two signals of fluorine at
–61.55 and –61.68 ppm (0.4 : 1.0) in 19F NMR
spectrum. At the same time the side chain is
characterized in the 13C NMR spectrum by one set of
signals including doublets at 35.71 ppm (PC=CHCαH2,
Hence, the formation of alkyl E-4-(furyl)-4-(di-
ethoxyphosphoryl)but-3-enoates in the reaction of
phosphorylated derivatives of furylacetic aldehyde is a
general rule for a broad range of 2- and 3-substituted
furan derivatives containing ester, nitrile, or trifluoro-
methyl group in the ring.
EXPERIMENTAL
1H, 13C, and 31P NMR spectra were taken on a
Bruker DPX-400 spectrometer [400.13 (1H), 161.97
(31P), 100.16 MHz (13C) respectively]. Melting points
were measured on a Boёtius apparatus.
Ethyl 5-[(diethoxyphosphoryl)methyl]-2-(trifluoro-
methyl)-3-furoate (3). To 4.0 g (13.29 mmol) of
bromide 2, 2.8 mL of triethyl phosphite was added.
The reaction mixture was heated to 160°C until the end
of ethyl bromide evolution. Vacuum distillation of
reaction mixture gave 3.02 g (63%) of phosphonate 3
1
3JPC = 18.0 Hz), 121.79 ppm (=CP, JPC = 185.6 Hz),
and 142.10 ppm (=CH, 2JPC = 7.2 Hz).
The reaction of nitrile 19 with ethoxycarbonylme-
thylenetriphenylphosphorane was carried out analogously,
but only triphenylphosphine oxide was isolated from
the reaction mixture. Evidently, the product of
condensation of this substance with phosphorane still
more eagerly undergoes polymerization than the com-
pounds containing no trifluoromethyl group [3].
1
as yellow oil of bp 154°C (1 mmHg). H NMR
spectrum, δ, ppm (J, Hz): 1.25 t (3H, CH3-ester, JHH
=
7.2), 1.28 t (6H, CH3-phosphonate, JHH = 7.2), 3.20 d
1
(2H, CH2P, JPH = 20.8), 4.08 q (2H, OCH2-ester,
JHH = 7.6), 4.09–4.11 m (4H, OCH2-phosphonate),
3
6.66 d (1H, H4-furan, JPH = 3.6). 13C NMR spectrum
(CDCl3), δС, ppm (J, Hz): 13.78 (CH3-ester), 16.15 d
In the reaction of formyl derivative 20 the abnormal
product 22 is also formed in a 61% yield (Scheme 10).
It has E-configuration as is well confirmed by spectral
data. Hence, despite of the presence of aldehyde 20a in
the equilibrium mixture of tautomers of phosphonate
20 and the occupation of position 2 of the furan ring
with substituent, Wittig condensation proceeds
unambiguously. As there is no strong base in the
reaction mixture, but-3-enoate derivative is formed
directly in the course of the reaction and not as a result
of subsequent prototropic isomerization. Note that
neighboring position of trifluoromethyl group and the
reaction center does not influence the result of the
reaction. It characterizes the difference of its effect
from that provided by the ester and nitrile group as
found previously [3].
3
1
(CH3-phosphonate, JPC = 3.2), 20.42 d (CH2P, JPC
=
142.8), 61.35 (OCH2-ester), 62.58 d (OCH2-phos-
phonate, 2JPC = 6.1), 62.61 (OCH2-phosphonate, 2JPC
=
3
6.0), 110.94 d (C3-furan, JPC = 6.7), 118.35 q (CF3,
1JFC = 267.4), 120.72 (C4-furan), 142.47 d.q (C5-furan,
2JCF = 42.6, 3JPC = 2.7), 148.16 d (C2-furan, 2JPC = 8.7),
160.50 (C=O). 19F NMR spectrum (CDCl3), δF, ppm:
–61.18(CF3). 31P NMR spectrum (CDCl3), δP, ppm:
20.76.
5-Methyl-2-(trifluoromethyl)furan-3-carboxamide
(6). In 10 mL of benzene was dissolved 1.39 g
(6.4 mmol) of acid chloride 5, the solution was cooled
on an ice bath and was treated with 3 mL of 25%
ammonia. The reaction mixture was stirred for 1h at
10°C. The obtained precipitate was filtered off and
dried in air until the constant mass. Yield 0.8 g (68%),
1
white powder. H NMR spectrum (DMSO-d6), δ, ppm
(J, Hz): 2.35 s (1H, CH3), 6.62 s (1H, H4-furan), 7.48 s
(1H, NH2), 7.81 s (1H, NH2). 13C NMR spectrum
(DMSO-d6), δC, ppm (J, Hz): 13.47 (CH3), 108.29 (C4-
Scheme 10.
PO(OEt)2
Ph3P=CH__COOEt
1
furan), 119.39 q (CF3, JFC = 266.3), 125.68 br.s (C3-
20
EtOOC
2
furan), 135.19 q (C2-furan, JFC = 43.3), 154.32 (C5-
furan), 162.12 (С=O). 19F NMR spectrum (DMSO-d6),
δF, ppm: –60.13 (CF3).
O
F3C
22
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SYNTHESIS AND WITTIG REACTION
247
5-Methyl-2-(trifluoromethyl)-3-cyanofuran (7).
To the suspension of 2.8 g (15.6 mmol) of amide 6 in
40 mL of carbon tetrachloride 3.26 g (15.6 mmol) of
phosphorus pentachloride was added in small portions
at vigorous stirring. The mixture formed was refluxed
with stirring for 2.5 h. Vacuum distillation gave 1.7 g
(62%) of nitrile 7 as a colorless oil with sweet scent,
bp 102–104°C (10 mmHg). 1H NMR spectrum
(CDCl3), δ, ppm (J, Hz): 2.43 s (1H, CH3), 6.37 s (1H,
H4-furan). 13C NMR spectrum (CDCl3), δС, ppm (J,
Hz): 13.33 (CH3), 99.67 (C3-furan), 108.74 (C4-furan),
5-(Chloromethyl)-2-(trifluoromethyl)furan-3-
carboxamide (11). To the cooled solution of 5.1 g
(21.9 mmol) of acid chloride 10 in 30 mL of benzene 4
mL of 25% ammonia was added. Five minutes later the
formation of white precipitate was observed. The
reaction mixture was stirred for 1.5 h at 5°C, the
precipitate was filtered off and dried in air until
constant mass. Yield 2.18 g (48%), white crystals, mp
60–62°C. 1H NMR spectrum (DMSO-d6), δ, ppm
(J, Hz): 4.91 s (2H, CH2Cl), 7.07 s (1H, H4-furan),
7.69 s (1H, NH2), 8.07 s (1H, NH2). 13C NMR
spectrum (DMSO-d6), δC, ppm (J, Hz): 36.78 (CH2Cl),
1
110.44 (CN), 117.70 q (CF3, JFC = 267.6), 145.22 q
2
1
(C2-furan, JFC = 42.9), 156.74 (C5-furan). 19F NMR
111.66 (C4-furan), 119.07 q (CF3, JFC = 266.8),
3
spectrum (CDCl3), δF, ppm: –63.75 (CF3).
125.83 q (C3-furan, JFC = 2.4), 139.71 q (C2-furan,
2JFC = 41.8), 152.67 (C5-furan), 161.68 (С=O). 19F
NMR spectrum (DMSO-d6), δF, ppm: –60.44 (CF3).
5-(Hydroxymethyl)-2-(trifluoromethyl)-3-furoic
acid (9). A mixture of 12.83 g (46 mmol) of
acetoxymethylfuran 8 and 5.7 g (101.2 mmol) of
potassium hydroxide in 50 mL of ethanol was stirred at
room temperature for a day. At the beginning a small
heat evolution was observed, the temperature of the
reaction mixture rose to 30°C. On the next day the
reaction mixture was acidified with saturated ethanol
solution of hydrogen chloride until pH 2, potassium
chloride precipitate was filtered off and washed with
15 mL of ethanol. Joined filtrates were evaporated to
dryness, the crystals formed were suspended in
chloroform, filtered, and dried in air until constant
mass. Yield 9.06 g (94%), light yellow crystals, mp
157°C. 1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz):
4.47 s (2H, CH2), 6.76 s (1H, H3-furan). 13C NMR spec-
trum (DMSO-d6), δC, ppm (J, Hz): 55.56 (CH2ОН),
5-(Chloromethyl)-2-(trifluoromethyl)-3-cyano-
furan (12). To a solution of 1.96 g (8.61 mmol) of
amide 11 in 7 mL of phosphorus oxychloride 30 mL of
carbon tetrachloride and 1.8 g (8.63 mmol) of
phosphorus pentachloride were added. The reaction
mixture was refluxed with stirring for 3 h, volatile
products were removed at a reduced pressure, and the
residue was distilled in a vacuum to give 1.65 g (92%)
of compound 12, light yellow liquid with bp 78–80°C
1
(1 mmHg). H NMR spectrum (CDCl3), δ, ppm (J,
Hz): 4.59 s (2H, CH2Cl), 6.75 s (1H, H4-furan). 13C
NMR spectrum (CDCl3), δС, ppm (J, Hz): 36.25
3
(CH2Cl), 100.06 q (C3-furan, JFC = 2.2), 109.64
(С≡N), 111.68 (C4-furan), 117.33 q (CF3, 1JFC = 268.7),
146.91 q (C2-furan, 2JFC = 43.2), 154.32 (C5-furan). 19F
NMR spectrum (CDCl3), δF, ppm: –63.77 (CF3).
1
110.06 (C4-furan), 119.05 q (CF3, JFC = 267.0),
3
121.95 q (C3-furan, JFC = 2.5), 140.81 q (C2-furan,
5-(Iodomethyl)-2-(trifluoromethyl)-3-cyanofuran
(13). To a solution of 3.24 g (17.41 mmol) of sodium
iodide dihydrate in 20 mL of acetone the solution of
1.83 g (8.74 mmol) of chloride 12 in 10 mL of acetone
was added. The reaction mixture was kept in the dark
for a day and then poured in 50 mL of 10% sodium
sulfite solution. The solution formed was extracted
with chloroform (25, 10, 10 mL), the extract was
washed with brine and dried over calcium chloride in
the dark. Chloroform was removed at a reduced
pressure, and the residue was kept in a vacuum
(1 mmHg) in the dark at room temperature for 1 h.
Yield 1.38 g (54%), yellow syrup. Liberation of iodine
under the action of light is rather slow. 1H NMR
spectrum (CDCl3), δ, ppm (J, Hz): 4.38 s (2H, CH2I),
6.70 s (1H, H4-furan). 13C NMR spectrum (CDCl3), δС,
2JFC = 41.5), 158.31 (C5-furan), 162.15 (С=O). 19F
NMR spectrum (DMSO-d6), δF, ppm: –60.27 (CF3).
5-(Chloromethyl)-2-(trifluoromethyl)-3-furoyl
chloride (10). To the suspension of 9.06 g (43 mmol)
of hydroxyl acid 9 in 30 mL of benzene the solution of
6.3 mL (86 mmol) of thionyl chloride in 20 mL of
benzene and 3 drops of DMF were added. The mixture
obtained was refluxed with stirring for a day. On the
next day vacuum distillation of reaction mixture gave
5.12 g (48%) of acid chloride 10 as yellow liquid of bp
1
88°C (1 mmHg). H NMR spectrum (CDCl3), δ, ppm
(J, Hz): 4.61 s (2H, CH2Cl), 6.99 q (1H, H4-furan, JHF
=
0.8). 13C NMR spectrum (CDCl3), δС, ppm (J, Hz):
35.45 (CH2Cl), 113.03 (C4-furan), 117.56 q (CF3, 1JFC
=
3
269.3), 123.83 q (C3-furan, JFC = 2.1), 144.19 q (C2-
2
furan, JFC = 44.0), 152.33 (C5-furan), 158.85 (С=O).
ppm (J, Hz): –11.88 (CH2I), 100.45 q (C3-furan, 3JFC
2.2), 109.72 (С≡N), 110.10 (C4-furan), 117.44 q (CF3,
=
19F NMR spectrum (CDCl3), δF, ppm: –62.79 (CF3).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 2 2018

248
DORONINA et al.
2
1JFC = 268.4), 146.05 q (C2-furan, JFC = 43.2), 155.97
(C5-furan). 19F NMR spectrum (CDCl3), δF, ppm:
–63.67 (CF3).
left overnight. On the next day it was washed with
7 mL of 5% hydrochloric acid, with 10 mL of
saturated sodium hydrogen carbonate solution, and
then with 10 mL of brine. The solution obtained was
dried over sodium sulfate and distilled in a vacuum to
give 1.17 g (48%) of chloride 17 as colorless oil with
Diethyl [5-(trifluoromethyl)-4-cyanofur-2-yl]me-
thanephosphonate (14). A mixture of 1.38 g
(4.59 mmol) of nitrile 13 and 2 mL of triethyl
phosphite was heated with stirring. The liberation of
ethyl iodide began at 110°C and completed at 160°C.
Total reaction time was 8 min. Vacuum distillation
gave 0.73 g (51%) of phosphonate 14 with bp 144–
1
bp 57°C (1 mmHg). H NMR spectrum (CDCl3), δ,
ppm (J, Hz): 2.34 s (3H, CH3), 4.51 s (2H, CH2Cl),
6.20 s (1H, H4-furan). 13C NMR spectrum (CDCl3), δС,
ppm (J, Hz): 13.28 (CH3), 34.89 (CH2Cl), 108.67 (C4-
furan), 119.58 q (CF3, 1JFC = 266.0), 124.92 (C3-furan),
135.93 q (C2-furan, 2JFC = 40.8), 155.01 (C5-furan). 19F
NMR spectrum (CDCl3), δF, ppm: –61.95 (CF3).
1
145°C (1 mmHg), light yellow viscous oil. H NMR
spectrum (CDCl3), δ, ppm (J, Hz): 1.34 t (6H, CH3,
2
JHH = 7.2), 3.29 d (2Н, СН2Р, JPH = 21.2), 4.12–4.19
m (4H, OCH2), 6.63 d (1H, H3-furan, JPH = 3.2). 13C
3
Diethyl
[2-(trifluoromethyl)-5-methylfur-3-yl]
methanephosphonate (15). To a solution of sodium
diethyl phosphite prepared from 1.5 mL of diethyl
hydrogen phosphite and 0.2 g of sodium in 20 mL of
benzene the solution of 1 g (5.03 mmol) of chloride 17
in 5 mL of benzene was added. The reaction mixture
was refluxed with stirring for 16 h, washed with 5 mL
of water, and dried over sodium sulfate. Vacuum
distillation gave 0.99 g (69%) of phosphonate 15 as
light yellow liquid of bp 115°C (1 mmHg). 1H NMR
spectrum (CDCl3), δ, ppm (J, Hz): 1.27 t (3H, CH3-
phosphonate, JHH = 7.2), 1.28 t (3H, CH3-phosphonate,
NMR spectrum (CDCl3), δС, ppm (J, Hz): 16.32 d
1
(CH3, 3JPC = 4.0), 26.66 d (CH2P, JPC = 142.9), 62.92
2
3
d (OCH2, JPC = 5.9), 100.22 q (C4-furan, JFC = 2.5)
109.99 (С≡N), 110.95 d (C3-furan, JPC = 6.6), 117.54
3
q (CF3, 1JFC = 268.2), 145.93 q (C5-furan, 2JFC = 42.6),
151.27 d (С2-furan, JPC = 8.0). 19F NMR spectrum
2
(CDCl3), δF, ppm: –63.73 (CF3). 31P NMR spectrum
(CDCl3), δP, ppm: 19.71.
[2-(Trifluoromethyl)-5-methylfur-3-yl]methanol
(16). To a suspension of 1 g (26.3 mmol) of lithium
aluminum hydride in 20 mL of diethyl ether the
solution of 3.92 g (17.7 mmol) of ester 1 in 10 mL of
diethyl ether was added at vigorous stirring at a rate
providing a slight boiling of the solvent. After that the
reaction mixture was stirred for a day. On the next day
15 mL of ethyl acetate was added dropwise with
stirring, and then saturated water solution of
ammonium chloride was added in small portions until
coagulation of grey inorganic precipitate. The organic
phase was decanted and dried over sodium sulfate.
Vacuum distillation gave 2.22 g (69%) of alcohol 16 as
JHH = 7.2), 2.29 s (3H, CH3), 3.04 d (2Н, СН2Р, JРH
=
21.6), 4.05–4.10 m (4H, OCH2), 6.16 s (1H, H4-furan).
13C NMR spectrum (CDCl3), δС, ppm (J, Hz): 13.40
3
(CH3), 16.23 d (CH3-phosphonate, JPC = 5.3), 22.95 d
1
(CH2P, JPC = 142.2), 62.26 d (OCH2-phosphonate,
3
2JPC = 6.2), 109.88 d (C4-furan, JPC = 3.0), 119.94 q
1
2
(CF3, JFC = 267.1), 118.78 d (C3-furan, JPC = 8.6),
136.45 d.q (C2-furan, JFC = 40.0, JCP 11.7), 154.38
(C5-furan). 19F NMR spectrum (CDCl3), δF, ppm:
–61.54 (CF3). 31P NMR spectrum (CDCl3), δP, ppm:
24.22.
2
3
1
colorless oil of bp 89–91°C (1 mmHg). H NMR
Ethyl 5-[1-(diethoxyphosphoryl)-2-oxoethyl]-2-
(trifluoromethyl)-3-furoate (18). To a solution of
3.0 g (8.38 mmol) of phosphonate 3 and 1.35 mL of
ethyl formate in 20 mL of benzene 0.23 g (10 mg-at)
of sodium foil was added. The reaction mixture was
stirred until complete dissolution of sodium and left
overnight. On the next day it was extracted with water
(2×10 mL), the water extract was washed with 10 mL
of ethyl acetate, acidified to pH 2–3 with hydrochloric
acid, and saturated with sodium chloride. The reaction
product was extracted with chloroform (3×10 mL) and
dried over sodium sulfate. Solvent was removed on a
rotary evaporator, and the residue was kept in a
vacuum (1 mmHg) at room temperature for 1 h. Yield
spectrum (CDCl3), δ, ppm (J, Hz): 2.31 s (3H, CH3),
2.62 s (1H, OH), 4.59 s (2H, CH2О), 6.16 s (1H, H4-
furan). 13C NMR spectrum (CDCl3), δС, ppm (J, Hz):
13.27 (CH3), 55.10 (CH2О), 107.93 (C4-furan), 119.87
q (CF3, 1JFC = 266.7), 128.02 (C3-furan), 134.94 q (C2-
2
furan, JFC = 40.9), 154.61 (C5-furan). 19F NMR
spectrum (CDCl3), δF, ppm: –61.58 (CF3).
2-(Trifluoromethyl)-3-(chloromethyl)-5-methyl-
furan (17). To a solution of 2.22 g (12.2 mmol) of
alcohol 16 and 1.2 mL of pyridine in 20 mL of ethyl
acetate the solution of 0.9 mL of thionyl chloride in 10 mL
of ethyl acetate was added dropwise with stirring and
cooling. The reaction mixture was stirred for a day and
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 2 2018

SYNTHESIS AND WITTIG REACTION
249
3
1.44 g (46%), light yellow viscous oil. In chloroform
compound 18 exists as a mixture of Z-enol 18a and
E-enol 18b in 1 : 0.2 ratio. 1H NMR spectrum (CDCl3),
δ, ppm (J, Hz): common signals: 1.27–1.33 m (9H,
CH3-ester, CH3-phosphonate) 4.06–4.21 m (6H, OCH2-
2JPC = 1.1); 19b: 16.40 d (CH3, JPC = 5.9), 62.75 d
(OCH2, 2JPC = 5.7), 91.75 d (CP, 1JPC = 179.1), 110.01
d (C3-furan, JPC = 8.3), 162.30 d (=С–OH, JPC
=
3
2
20.7). 19F NMR spectrum (CDCl3), δF, ppm: –61.48
(CF3, 19a), –61.56 (CF3, 19b). 31P NMR spectrum
(CDCl3), δP, ppm: 17.37 (19b), 19.06 (19а).
ester, OCH2-phosphonate), 11.58 br.s (1Н, OH); 18a:
2
6.54 s (1H, H3-furan), 7.87 d (1H, =СН–О, JPH
=
Diethyl 1-[5-methyl-2-(trifluoromethyl)fur-3-yl]-
2-oxoethylphosphonate (20). To a solution of 1.14 g
(4.01 mmol) of phosphonate 15 and 0.7 mL of ethyl
formate in 10 mL of benzene 0.1 g (4.34 mg-at) of
sodium foil was added. The reaction mixture was
stirred until complete dissolution of sodium and left
overnight. On the next day the reaction mixture was
extracted with water (3×5 mL), water extract was
washed with 5 mL of ethyl acetate, saturated with
sodium chloride, and acidified with hydrochloric acid
to pH 2–3. The reaction product was extracted with
chloroform and dried over sodium sulfate, the solvent
was removed on a rotary evaporator, and the residue
was kept in a vacuum (1 mmHg) at room temperature
for 1 h. Yield 0.36 g (26%), yellow viscous oil. In the
solution compound 20 exists as a mixture of aldehyde
20a, E-enol 20b and Z-enol 20c in 0.3 : 1.0 : 0.7 ratio.
1H NMR spectrum (CDCl3), δ, ppm (J, Hz): common
signals: 1.29 t (3H, CH3-phosphonate, JHH = 7.2), 1.35
t (3H, CH3-phosphonate, JHH = 7.0), 3.99–4.23 m (4H,
OCH2-phosphonate); 20а: 2.37 s (3H, CH3), 4.53 d
38.4); 18b: 7.03 (1H, H3-furan), 7.73 d (1H, =СН–О,
2JPH = 10.4). 13C NMR spectrum (CDCl3), δС, ppm
(J, Hz): common signals: 13.89 (CH3-ester), 16.04 d
3
(CH3-phosphonate, JPC = 6.4), 61.5 (OCH2-ester),
2
63.07 d (OCH2-phosphonate, JPC = 4.7), 118.57 q
(CF3, JFC = 267.5), 141.05 q (C5-furan, JFC = 42.2),
1
2
149. 85 d (C2-furan, 2JPC = 16.5), 163.99 (C=O); 18a:
1
3
91.09 d (CP, JPC = 180.5), 110.57 d (C3-furan, JPC
=
7.6), 121.02 (C4-furan), 160. 83 (=С–OH); 18b: 92.02
d (CP, JPC = 202.8), 110.08 d (C3-furan, JPC = 5.9),
120.75 (C4-furan), 161. 03 d (=С–OH, 2JPC = 20.6). 19F
NMR spectrum (CDCl3), δF, ppm: –61.33 (CF3, 18a),
–61.36 (CF3, 18b). 31P NMR spectrum (CDCl3), δP,
ppm: 18.42 (18b), 19.88 (18a).
1
3
Diethyl 1-[4-cyano-5-(trifluoromethyl)fur-2-yl]-
2-oxoethylphosphonate (19). To a solution of 0.68 g
(2.18 mmol) of phosphonate 14 and 0.4 mL of ethyl
formate in 20 mL of benzene 0.06 g (2.6 mg-at) of
sodium foil was added, and the reaction mixture was
stirred for 6 h. Dissolution of sodium proceeded with
slight heat evolution. On the next day the reaction
mixture was extracted with water (2×10 mL), water
extract was washed with 5 mL of ethyl acetate and
acidified with hydrochloric acid to pH 3. The mixture
formed was saturated with sodium chloride and
extracted with chloroform (3×8 mL). The extract was
dried with sodum sulfate, the solvent was removed on
a rotary evaporator, and the residue was kept in a
vacuum (1 mmHg) at room temperature for 1 h. Yield
0.29 g (39%), light yellow viscous oil. In chloroform
compound 19 exists as a mixture of Z-enol 19a and
E-enol 19b in 1 : 0.2 ratio. 1H NMR spectrum
(CDCl3), δ, ppm (J, Hz): common signals: 4.08–4.24
m (4H, OCH2), 11.75 br.s (1H, OH); 19a: 1.37 t (6H,
CH3, JHH = 7.0), 6.30 s (1H, H3-furan), 7.92 d (1H,
=СН–О, JPH = 39.2); 19b: 1.27 t (6H, CH3, JHH = 7.0),
6.93 (1H, H3-furan), 7.78 d (1H, =СН–О, JPH = 10.4).
13C NMR spectrum (CDCl3), δС, ppm (J, Hz): common
(1H, PCH, JPH = 28.0), 6.40 s (1H, H4-furan), 9.76 s
1
(1H, CHO); 20b: 2.32 s (3H, CH3), 6.01 s (1H, H4-
furan), 7.61 d (1H, =СН, 2JPH = 10.0). 20c: 2.32 s (3H,
CH3), 6.50 s (1H, H4-furan), 7.24 d.d (1H, =CH–О, JPH
=
40.0, JHН = 12.0), 11.17 d (OH, JHН = 12.0). 13C NMR
spectrum (CDCl3), δС, ppm (J, Hz): common signals:
3
16.06 d (CH3-phosphonate, JPC = 6.9), 16.10 d (CH3-
3
phosphonate, JPC = 6.8), 16.24 d (CH3-phosphonate,
3JPC = 5.8), 16.39 d (CH3- phosphonate, JPC = 5.9),
3
2
63.49 d (OCH2-phosphonate, JPC = 7.0), 63.77 d
2
(OCH2-phosphonate, JPC = 7.0), 61.95 d (CH2O-
phosphonate, 2JPC = 5.1), 62.54 d (CH2O-phosphonate,
2JPC = 4.9); 20a: 13.55 (CH3), 50.12 d (PC, JPC
=
1
129.6), 109.28 d (С4-furan, 3JPC = 2.2), 118.39 d.q (C3-
2
3
1
furan, JPC = 7.7, JFC = 3.0), 119.72 q (CF3, JFС
265.7), 136.68 d.q (C2-furan, JFC = 40.0, JCP 10.3),
2
3
154. 92 (C5-furan), 191.75 (C=O); (20b): 13.50 (CH3),
88.90 d (PC=, JPC = 181.4), 110.10 s (C4-furan),
1
signals: 100.59 q (С4-furan, JCF = 2.2), 110.18 (CN),
119.86 (CF3, 1JFC = 267.2), 121.56 d.q (C3-furan, 2JPC
=
=
=
=
=
3
117.69 q (CF3, 1JFC = 267.6), 144.14 q (C5-furan, 2JFC
=
7.9, JFC = 2.3), 135.72 (C2-furan, JFC = 39.9, JPC
3
2
3
42.9), 152. 81 d (C2-furan, 2JPC = 17.2); 19a: 16.11 d
10.9), 154.11 (C5-furan), 159.55 br.d (=С–OH, JPC
2
3
2
1
(CH3, JPC = 6.4), 63.31 d (OCH2, JPC = 4.9), 90.09 d
(CP, 1JPC = 180.5), 106.12 (C3-furan), 164.87 d (=С–OH,
25.9); (20c): 13.50 (CH3), 91.34 br.d (PC, JPC
205.7), 110.10 s (C4-furan), 119.86 q (CF3, JFC
1
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 2 2018

250
DORONINA et al.
2
3
267.2), 121.56 d.q (C3-furan, JPC = 7.9, JFC = 2.3),
furan), 3.06 d.d (2H, CР=CHCH2, JHH = 7.0, JPH =
135.72 (C2-furan, 2JFC = 39.9, 3JPC = 10.9), 154.11 (C5-
3.4), 4.00–4.08 m (4H, OCH2-phosphonate), 4.09 q
(2H, OCH2-ester, JHH = 7.2), 5.97 s (1H, H4-furan),
6.99 d.t (1H, PC=CH, 1JPH = 21.6, JHH = 7.0). 13C NMR
4
furan), 163.77 q (=С–OH, JFC = 2.4). 19F NMR
spectrum (CDCl3), δF, ppm: –60.11 (CF3, 20c), –61.27
(CF3, 20a), –63.43 (CF3, 20b). 31P NMR spectrum
(CDCl3), δP, ppm: 16.19 (20a), 21.44 (20b), 22.04 (20c).
spectrum (CDCl3), δС, ppm (J, Hz): 13.41 (СН3-furan),
3
13.99 (СH3-ester), 16.12 d (СH3-phosphonate, JPC
=
6.4), 35.28 d (PC=CHCαH22, 3JPC = 18.1), 61.05 (CH2О-
Ethyl E-4-[4-carbethoxy-5-(trifluoromethyl)fur-
2-yl)]-4-(diethoxyphosphoryl)but-3-enoate (21). A
mixture of 0.65 g (1.86 mmol) of ethoxycarbonylme-
thylenetriphenylphosphorane, 0.6 g (1.35 mmol) of
formyl derivative 18, and 10 mL of benzene was
stirred for 8 h at 70°C, diluted with 25 mL of light
petroleum ether, and left overnight for crystallizaton of
triphenylphosphine oxide. The precipitate formed was
filtered off, and the solvent was removed from filtrate
at a reduced pressure. The residue was kept in a
vacuum (1 mmHg) at room temperature for 1 h. Yield
ester), 62.29 d (CH2OP, JPC = 5.5), 109.60 d (С4-
furan, 3JPC = 1.8), 119.36 d.q (CF3, 1JFC = 266.6, 4JPC
=
1.5), 120.99 d.q (С3-furan, JPC = 10.1, JFC = 2.4),
2
3
124.69 d (=CP, JPC = 188.1), 135.96 d.q (С2-furan,
1
3JPС 8.9, JFС 43.1), 141.97 d (=СН, JPC = 10.9),
154.89 (C5-furan), 169.37 (C=O). 19F NMR spectrum
(CDCl3), δF, ppm: –62.59 (CF3). 31P NMR spectrum
(CDCl3), δP, ppm: 14.37.
2
2
ACKNOWLEDGMENTS
1
1.11 g (80%), yellow oil. H NMR spectrum (CDCl3),
δ, ppm (J, Hz): 1.25–1.37 m (12H, СH3-ester, СH3-
phosphonate), 3.60 d.d (1.4H, CР=CHCH2, JHH = 7.0,
The work was carried out within the framework of
the basic part of the State project of the Ministry of
education and science of Russia, project no
4.5554.2017/8.9.
J
PH = 3.2), 3.89 d.d (0.6H, PC=CHCH2, JHH = 7.0, JPH =
3.2), 4.08–4.21 m (8H, OCH2-ester, OCH2-phos-
phonate), 7.06 s (1H, H3-furan), 7.13 d.t (1H, PC=CH,
1JPH = 23.2, JHH = 7.0). 13C NMR spectrum (CDCl3),
δС, ppm (J, Hz): 13.91 (СH3-ester), 14.07 (СH3-ester),
REFERENCES
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3
16.2 d (СH3-phosphonate, JPC = 6.2), 35.71 d
(PC=CHCαH2, JPC = 18.0), 61.31 (CH2О-ester), 61.65
3
2
(CH2О-ester), 62.49 d (CH2OP, JPC = 4.7), 62.78 d
(CH2OP, JPC = 5.3), 113.74 (С3-furan), 120.82 br.s
2
(С4-furan), 118.40 q (CF3, JFC = 267.9), 121.79 d
1
1
2
(=CP, JPC = 185.6), 142.10 d (=СН, JPC = 7.2),
3. Pevzner, L.M., Russ. J. Gen. Chem., 2017, vol. 87,
142.82 q (С5-furan, JFC = 42.9), 149.75 d (C2-furan,
2
no. 7, p. 1516. doi 10.1134/S107036321707012X
2JPC = 21.6), 160.43 (furan-C=O), 169.57 (C=O). 19F
NMR spectrum (CDCl3), δF, ppm: –61.55 (CF3, 0.4),
–61.68 (CF3, 1.0). 31P NMR spectrum (CDCl3), δP,
ppm: 11.87 (0.4), 14.03 (1.0).
4. Bambury, R.E., Yaktin, H.K., and Wyckoff, K.K.,
J. Heterocycl. Chem., 1968, vol. 5, p. 95. doi 10.1002/
jhet.557005115
5. Lyalin, V.V., Grigorash, R.V., Alekseeva, L.M., and
Yagupolskii, L.M., Zh. Org. Khim. USSR, 1984, vol. 20,
no. 4, p. 769.
6. Pretsch, E., Bühlmann, P., and Affolter, C., Structure
Determination of Organic Compounds: Tables of Spectral
Data, New York: Springer, 2000.
Ethyl E-4-[5-methyl-2-(trifluoromethyl)fur-3-yl]-
4-(diethoxyphosphoryl)but-3-enoate (22). This com-
pound was prepared analogously from 0.33 g (0.94 mmol)
of ethoxycarbonylmethylenetriphenylphosphorane and
0.26 g (0.80 mmol) of formyl derivative 20. Yield 0.19 g
(61%), light brown oil. 1H NMR spectrum (CDCl3), δ,
ppm (J, Hz): 1.19 t (3H, СH3-ester, JHH = 7.2), 1.25 t
(6H, СH3-phosphonate, JHH = 7.0), 2.29 s (3Н, СН3-
7. Pevzner, L.M., Russ. J. Gen. Chem., 2014, vol. 84,
no. 11, p. 2147. doi 10.1134/S1070363214110118
8. Breuer, E. and Moshe, R., Israel J. Chem., 1981,
vol. 27, no. 1, p. 45. doi 10.1002/ijch.198000008
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