Synthesis and Selected Reactions of 2(3)-Furoyl Phosphonates Functionalyzed at the Neighbor Position of the Furan Ring

Article abstract of DOI:10.1134/S1070363219080103

Reactions of 2-and 3-furoyl chlorides having chloromethyl or butylthiomethyl group in the adjacent position of the furan ring as well as of analogous N-morpholinomethylfuroyl chloride hydrochlorides with triethyl phosphite have been studied. The synthesized chloromethylfuroyl phosphonates have given the corresponding products of nucleophilic substitution in the reactions with sodium azide and potassium thiocyanate in the case of 4-chloromethyl-3-furoyl phosphonate. In the reaction of 3-chloromethyl-2-furoyl phosphonate with sodium azide, cleavage of the P-C bond takes place simultaneously with nucleophilic substitution. Potassium thiocyanate forms 3-thiocyanatomethyl-2-furoyl phosphonate in the reaction with this substance. The synthesized stable furoyl phosphonates enter the Wittig reaction with resonance-stabilized phosphoranes to give phosphorylated furylalkenes. If these compounds carry a chloromethyl group in the furan ring, they react with sodium azide and potassium thiocyanate to give the corresponding products of nucleophilic substitution. Analogously, aminomethyl derivatives have been obtained in the reaction with morpholine at room temperature.

Full text of DOI:10.1134/S1070363219080103

ISSN 1070-3632, Russian Journal of General Chemistry, 2019, Vol. 89, No. 8, pp. 1604–1619. © Pleiades Publishing, Ltd., 2019.
Russian Text © The Author(s), 2019, published in Zhurnal Obshchei Khimii, 2019, Vol. 89, No. 8, pp. 1216–1232.
Synthesis and Selected Reactions of 2(3)-Furoyl Phosphonates
Functionalyzed at the Neighbor Position of the Furan Ring
L. M. Pevznera* and N. B. Sokolovaa
a St. Petersburg State Institute of Technology (Technical University), Moskovskii pr. 26, St. Petersburg, 190013 Russia
*e-mail: pevzner_lm@list.ru
Received February 8, 2019; revised February 8, 2019; accepted February 14, 2019
Abstract―Reactions of 2-and 3-furoyl chlorides having chloromethyl or butylthiomethyl group in the adjacent
position of the furan ring as well as of analogous N-morpholinomethylfuroyl chloride hydrochlorides with triethyl
phosphite have been studied. The synthesized chloromethylfuroyl phosphonates have given the corresponding
products of nucleophilic substitution in the reactions with sodium azide and potassium thiocyanate in the case of
4-chloromethyl-3-furoyl phosphonate. In the reaction of 3-chloromethyl-2-furoyl phosphonate with sodium azide,
cleavage of the P–C bond takes place simultaneously with nucleophilic substitution. Potassium thiocyanate forms
3-thiocyanatomethyl-2-furoyl phosphonate in the reaction with this substance. The synthesized stable furoyl phos-
phonates enter the Wittig reaction with resonance-stabilized phosphoranes to give phosphorylated furylalkenes.
If these compounds carry a chloromethyl group in the furan ring, they react with sodium azide and potassium
thiocyanate to give the corresponding products of nucleophilic substitution.Analogously, aminomethyl derivatives
have been obtained in the reaction with morpholine at room temperature.
Keywords: furoyl chlorides, Arbuzov reaction, furoyl phosphonates, Wittig reaction, nucleophilic substitution
DOI: 10.1134/S1070363219080103
We have recently investigated the methods of synthesis
and chemical properties of furoyl phosphonates bearing a
functional group remote from the phosphorus-containing
substituent [1, 2]. Extending those studies, we turned to
furoyl phosphonates with a substituent adjacent to the
acyl phosphonate group. This study aimed to elucidate
the influence of the neighbor substituent on the course
of the Arbuzov reaction and to investigate nucleophilic
substitution reactions in such furoyl phosphonates when
the adjacent substituent was a chloromethyl group. It
was also proposed to study the features of the Wittig
reaction with resonance-stabilized phosphoranes for the
above-mentioned furoyl phosphonates, as well as the
nucleophilic substitution reactions of phosphorylated
chloromethylfurylalkenes formed via the Wittig process.
Acyl chlorides 1, 3, and 5 were chosen as the starting
compounds for the preparation of chloromethylfuroyl
phosphonates. The reaction was carried out at the acid
Scheme 1.
CH2Cl
PO(OEt)2
CH2Cl
P(OEt)3
O
COCl
O
O
1
2
ClOC
O
CH2Cl
P(OEt)3
CH2Cl
OP
(EtO)2
O
O
3
4
1604

SYNTHESIS AND SELECTED REACTIONS OF 2(3)-FUROYL PHOSPHONATES
1605
Scheme 2.
O
Cl
PO(OEt)2
COCl
O
9
PO(OEt)3
O
5
CH2Cl
COCl
O
u
COOH
PO(OEt)2
P(OEt)3
SOCl2
DMF
Cl
O
Cl
O
Cl
O
8
6
7
chloride : triethyl phosphite molar ratio of 1 : 1.05 in
benzene at room temperature. In the case of acid chlorides
1 and 3, the corresponding furoyl phosphonates 2, 4 were
obtained in 96 and 98% yield, respectively (Scheme 1).
proton at 6.56 ppm, and the signals of the furan ring
carbon atoms nuclei were located at 108.34 (C4), 120.25
(C3), 135.88 (C5), and 160.82 ppm (C2).
The Arbuzov reaction of acid chloride 8 with triethyl
phosphite was carried out at room temperature in ben-
zene and led to the formation of furoyl phosphonate 6
in 98% yield (Scheme 2). It turned out to be labile and
could not be distilled in vacuum. While handling, it was
split with air moisture with liberation of diethyl hydro-
gen phosphite and acid 7. The NMR spectra contained a
signal of phosphorus nucleus at –2.19 ppm, a broadened
signal of the methyl group was observed at 2.55 ppm, and
the signal of the furan ring proton H3 was found at 6.95
ppm. The signals of the furan ring carbon atoms nuclei
were located at 107.16 (C4, 3JPC = 2.0 Hz), 122.06 (C3,
1
The H NMR spectrum of compound 2 contained two
signals of chloromethyl group at 4.76 and 4.82 ppm. The
furan ring proton H4 was also revealed by two signals
at 6.78 ppm (br. s) and 6.80 ppm (d, JHH = 2.6 Hz). The
only broadened signal of the H5 furan ring proton was
located at 7.66 ppm.
The reaction of 2-chloromethyl-3-furoyl chloride
5 under those conditions occurred differently. A stable
substance with bp 144–146°C (1 mmHg) was isolated
from the reaction mixture. Chemical shift of phosphorus
in that substance was –2.33 ppm, characteristic of acyl
phosphonates. Its 1H NMR spectrum contained a signal
of the methyl group protons at 2.59 ppm, and the signal
of the furan ring proton was located at 7.06 ppm. The 13C
2JPC = 68.8 Hz), 135.57 (C5), and 160.36 ppm (C2, 3JPC
=
14.5 Hz). The signal of the carbonyl group carbon atom
was found at 193.24 ppm (1JPC 184.2 Hz). Hence, stability
and spectral properties of the obtained compounds were
clearly different. That is why the substance obtained from
acid chloride 5 via the Arbuzov reaction was considered
to be 2-methyl-4-chloro-3-furoyl phosphonate.
NMR spectrum contained the signals of the furan ring
2
carbon atom nuclei at 121.16 (C4), 122.63 (C3, JPC
=
=
3
68.7 Hz), 142.76(C5), and 162.54 ppm (C2, JPC
14.5 Hz). The signal of the carbonyl group carbon atom
nucleus was found at 193.12 ppm (1JPC = 184.1 Hz).
High-resolution mass spectrometry data showed that the
molecule contained one chlorine atom. We suggested that
the formed substance was 2-methyl-5-chloro-3-furoyl
phosphonate 6 and carried out its counter synthesis start-
ing from the reported 2-methyl-5-chloro-3-furoic acid 7
[3]. Its refluxing in benzene with thionyl chloride in the
presence of DMF led to the formation of labile acid chlo-
ride 8 with bp 69°C (1 mmHg) in 24% yield (Scheme 2).
The NMR spectra contained the signal of the furan ring
Furoyl phosphonates 2 and 4 were involved in nucleo-
philic substitution reactions with potassium thiocyanate
and sodium azide. The reaction of compound 2 with
potassium thiocyanate was carried out in acetonitrile at
room temperature (Scheme 3). The thiocyanate : phos-
phonate molar ratio was 2 : 1, potassium iodide was used
as catalyst (10 mol %). Thiocyanate 10 was the reaction
product (83% yield). The formation of the C–S bond was
confirmed by means of NMR spectroscopy. The signal of
protons of the H2CS fragment was located at 4.33 ppm,
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1606
PEVZNER, SOKOLOVA
Scheme 3.
CH2SCN
PO(OEt)2
KSCN
KI
O
O
2
10
N
CH2
3
NaN3
KI
+
HPO(OEt)2
N3
O
O
11
and the signal of the corresponding carbon atom was
observed at 28.27 ppm. The signal of the CN carbon atom
was revealed at 111.68 ppm.
13 was formed in 88% yield. It was decomposed when
heated above 50oC.
Further, we decided to investigate the applicability of
theArbuzov reaction for obtaining of aminomethylfuroyl
phosphonates starting from aminomethylfuroyl chlorides
hydrochlorides analogously to [2]. Hydrochlorides 14–16
were prepared from halomethyl derivatives of the cor-
responding furoates (Scheme 5). The reaction scheme is
exemplified by the synthesis of compound 14. The reac-
tion of bromide 17 with morpholine was carried out at
room temperature in benzene during 10 h, the obtained
amino ester 18 was hydrolyzed for 8 h with ethanolic
solution of potassium hydroxide at 80°C and then treated
with 2 mol of hydrogen chloride solution in ethanol. Crys-
talline hydrochloride of the amino acid 19 was isolated
via evaporation of the ethanolic solution and treatment
of the residue with 1 : 1 vol/vol mixture of acetone and
ethyl acetate. For conversion into acid chloride 14, it was
refluxed for 6 h in thionyl chloride.
The reaction with sodium azide was carried out simi-
larly, but the process was complete in a week because of
low solubility of azide in acetone (Scheme 3). It turned
out that the cleavage of the P–C bond with the elimina-
tion of sodium diethyl phosphite occurred, along with
substitution of halogen. Sodium diethyl phosphite reacted
with air moisture to give diethyl hydrogen phosphite (PH,
6.79 ppm, 1JPH = 692.8 Hz, δP 7.33 ppm). The formation
of the azidomethyl group was confirmed by the presence
of the signal of the methylene group protons at 4.64
ppm and the signal of the corresponding carbon atom at
45.60 ppm. Chemical shifts of the azido group nitrogen
atoms were evaluated by means of NH-correlations, N1
249 and N2 73 ppm, in agreement with the reference
data [4]. The IR spectrum contained an absorption band
at 2102 cm–1, characteristic of aliphatic azido group [5].
The formation of acylazido group via the cleavage of the
P–C bond was confirmed by the presence of the bands at
2141 (acyl azide) and 1687 cm–1 (C=O), in good agree-
ment with the reference data [6] on furoyl azides. Overall,
the obtained data allowed assignment of structure 11 to
the obtained diazide. Since we failed to remove diethyl
hydrogen phosphite from compound 11, its yield (70%)
was calculated on the basis of relative intensities of the
signals of furan and diethyl hydrogen phosphite in the 1H
NMR spectrum and total mass of the sample.
Scheme 4.
O
CH2SCN
OP
(EtO)2
KSCN
KI
O
12
4
O
NaN3
KI
Chloromethylfuroyl phosphonate 4 was completely
converted to thiocyanatomethyl derivative 12 under the
analogous conditions (24 h, yield 99%) (Scheme 4). The
reaction of compound 4 with sodium azide was completed
in 48 h at room temperature, the azidomethyl derivative
N
CH2
3
(EtO)2OP
O
13
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SYNTHESIS AND SELECTED REACTIONS OF 2(3)-FUROYL PHOSPHONATES
1607
Scheme 5.
HCl
N
O
N
O
Br
CH2
HN
O
(1) KOH, EtOH
(2) HCl, EtOH
COOMe
COOMe
O
O
COOH
O
17
18
19
HCl
N
N
O
O
, N(Et)
P(OEt)3
3
SOCl2
O
N(Et) ·HCl
ꢀ
3
PO(OEt)2
O
COCl
14
O
O
20
Scheme 6.
O
P(OEt)2
O
COCl
O
O
N(Et)
·HCl
P(OEt)
,
3
3
N
N
ꢀ
N(Et)3
O
O
HCl
21
15
Scheme 7.
O
HCl
COCl
, N(Et)
P(OEt)3
N
PO(OEt)2
N
3
·HCl
N(Et)
ꢀ
O
O
3
O
O
22
16
The reaction of furoyl chloride hydrochloride 14 with
triethyl phosphite was carried out in benzene at the acid
chloride : phosphite molar ratio of 1 : 1.02 in the pres-
ence of 1 mol of triethylamine at room temperature for
12 h. The major reaction product occurred to be mixed
anhydride of furoic and phosphoric acids 20, which
was isolated in 78% yield (Scheme 5). The signal of
the phosphorus in its NMR spectrum was observed at
0.98 ppm, and singlet of the carbonyl carbon atom nucleus
was found at 151.51 ppm.
Furoyl chloride 16 formed furoyl phosphonate 22 in
86% yield under the same conditions (Scheme 7). The
signal of phosphorus nucleus in the 31P NMR spectrum
was found at –3.19 ppm, the doublet of carbonyl carbon
atom was located at 194.06 ppm (1JPC = 179.5 Hz), and
the doublet of the C3 carbon atom of the furan ring was
observed at 125.59 ppm (2JPC = 69.4 Hz).
Hence, the reaction of morpholinomethylfuroyl chro-
ride hydrochloride with triethyl phosphite proceeded
likely via two pathways. One of them consisted in deal-
kylation of triethyl phosphite with triethylamine hydro-
chloride to give ethyl chloride and ester salt of diethyl
phosphite. The phosphorus atom of the latter preferably
existed in the three-coordinate state. Further nucleophilic
substitution of chlorine yielded mixed ester anhydride of
carboxylic and phosphorous acid. Depending on the ease
of oxidation, that compound was found as such (product
21) or as the phosphate (product 20). The alternative
The reaction of acid chloride 15 was carried out
similarly, but the major product was mixed anhydride of
furoic and phosphorous acids 21 (yield 65%, Scheme 6).
Chemical shift of phosphorus in that compound was
138.74 ppm, in good agreement with the reported data on
mixed anhydrides of carboxylic and phosphorous acids
[7]. The 13C NMR spectrum contained the signal of the
carbonyl carbon atom nucleus at 160.54 ppm.
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PEVZNER, SOKOLOVA
Scheme 8.
O
O
BuSH
2C
ClH2C
COOEt
BuSH
O
2C
BuSH
OEt
(1) KOH, EtOH
(2) HCl
OH
K
2CO3
O
O
O
25
24
26
BuSH
2C
BuSH
2C
COCl
P(OEt)3
SOCl2
DMF
PO(OEt)2
O
O
27
23
pathway was the Arbuzov reaction (product 22). In the
case of 2,3-disubstituted furans, the first pathway was the
of the substituent on the reaction with triethyl phosphite
was revealed only for morpholinomethylfuroyl chlorides.
major one, whereas the second pathway was predominant
for the 3,4-disubstituted substrates.
The synthesized furoylphosphonates were introduced
in the Wittig reaction with resonance-stabilized phos-
phoranes (Scheme 10). The reaction was carried out in
boiling benzene, the phosphonate : phosphorane molar
ratio being 1 : 1.1. The reaction progress was monitored
by 31P NMR spectroscopy following gradual decrease in
the intensity of the acyl phosphonate phosphorus signal.
The next stage of this study was investigation of furoyl
phosphonates bearing a butylthiomethyl substituent ad-
jacent to the acyl phosphonate position. The synthesis of
the starting acid chlorides was carried out according to the
same scheme which is shown in Scheme 8 for compound
23. Halomethylfuroate 24 gave butylthiomethyl deriva-
tive 25 in 84% yield when treated with butanethiol at the
halide : thiol molar ratio = 1 :1.1 in acetonitrile at 30–40°C
in the presence of solid potassium carbonate. The product
hydrolysis with ethanolic potassium hydroxide solution
followed by acidifying gave acid 26 in 67% yield. Sub-
sequent treatment with thionyl chloride in benzene in the
presence of DMF at boiling led to furoyl chloride 27 in
96% yield. Acid chloride 28 was obtained similarly. In
the case of acid 30, the reaction with thionyl chloride was
complex. Singlet of protons of the furan-CH2S fragment
and triplet of protons of the SCH2 of butyl substituent
The reaction was complete in 9–10 h, no certain de-
pendence on the structure of substrate and nature of the
phosphorane was found. The reaction proceeded stere-
oselectively to give the compounds with trans-location
of the phosphonate and carbonyl group with respect to
the double bond.
The reaction of acyl phosphonate 2 with acetylmethy-
lenetriphenylphosphorane 32 resulted in the formation
of unsaturated ketone 33. The signal of the phosphorus
nucleus of that compound was observed at 12.71 ppm,
the signal of the protons of the ketone methyl group was
located at 2.05 ppm, and a doublet of olefinic proton was
observed at 7.13 ppm (JPH = 22.0 Hz). A broad signal of
the carbon atom of the ketone methyl group was found at
29.68 ppm, a doublet of the C1 carbon atom at the double
bond was observed at 131.77 ppm (2JPC = 3.1 Hz), a dou-
blet of the C1 carbon atom at the double bond was found
1
were absent in the H NMR spectrum of the obtained
compound. Instead of those, several multiplets were ob-
served at 3.6–3.9 ppm. While handling, that sample was
rapidly converted into fragile insoluble mass evidencing
the formation of a crosslinked polymer.
Acid chlorides 23 and 28 reacted with triethyl phos-
phite at room temperature via theArbuzov scheme to give
acyl phosphonates 27, 29 bearing butylthiomethyl group
in the positions 4 or 2 of the furan ring (Scheme 9). Yield
of obtained compounds was 96 and 95%, respectively.
Scheme 9.
O
COCl
PO(OEt)2
CH2SBu
P(OEt)3
Hence, a series of 2- and 3-furoyl phosphonates hav-
ing functional group in the adjacent position of the furan
ring was prepared via the Arbuzov reaction. The effect
CH2SBu
O
O
29
28
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SYNTHESIS AND SELECTED REACTIONS OF 2(3)-FUROYL PHOSPHONATES
1609
Scheme 10.
CH2SCN
PO(OEt)2
O
O
KSCN
CH2Cl
PO(OEt)2
O
34
Ph3P
Ph P=O
3
2 +
ꢀ
O
O
N
CH2
3
32
NaN3
PO(OEt)2
O
3
3
O
35
at 128.97 ppm (1JPC = 179.0 Hz), and a doublet of the
carbon atom of the ketone carbonyl group was observed
at 198.67 ppm (3JPC = 20.2 Hz).
ditions. The yield of 4-furylbut-3-en-2-one 37 was 80%,
and that of 3-(furyl)acrylate 38 was 86% (Scheme 11).
Those substances were stable in air and in solutions at
moderate heating.
Considering that thiocyanatomethylfuroyl phospho-
nate 10 decomposed under the probed conditions of the
Wittig reaction, and analogous azidomethyl derivative
was not formed via nucleophilic substitution of chlorine
in compound 2, we involved the unsaturated ketone 33
in the reactions with potassium thiocyanate and sodium
azide (Scheme 10). The substitution was carried out in
acetonitrile at the phosphonate : nucleophile molar ratio of
1 : 2 in the presence of 10 mol % of potassium iodide. The
reaction of potassium thiocyanate with halomethylketone
33 was complete during a day at room temperature and
proceeded exclusively at the sulfur atom. Thiocyanate
34 was isolated in 54% yield. The formation of thiocya-
nate group was confirmed by the presence of the signal
of thiocyanatomethyl group protons at 4.21 ppm, the
signal of the corresponding carbon atom at 29.51 ppm,
and the signal of the carbon atom of the –SCN fragment
at 112.68 ppm.
4-Substituted 3-furoyl phosphonates 4, 12 and 27
were also introduced in the reactions with phosphoranes
32 and 36 under the above-used conditions. The yield of
the chloromethyl (39, 40) and butylthiomethyl (42, 43)
derivatives was of 80–90%, while the yield of thiocyana-
tomethyl derivative 41 was as low as 54% (Scheme 12).
Chloromethyl derivatives 39, 40 were involved in the
nucleophilic substitution reactions with amines. It was
found that those reactions were complicated at elevated
temperatures, but at 25°C smooth substitution of chlorine
with morpholine residue occurred. The corresponding un-
saturatedaminophosphonatesofthefuranseries44,45were
Scheme 11.
O
Ph3P
PO(OEt)2
CH2SBu
O
ꢀ
Ph3P=O
The reaction of compound 33 with sodium azide was
carried out at 70°C due to low solubility of the azide in
acetonitrile. The reaction was complete in 9 h and was
accompanied by considerable decomposition. The signal
of the azidomethyl group protons in the NMR spectrum
of the product was revealed at 4.25 ppm, and that of the
corresponding carbon atom was found at 45.59 ppm.
O
37
EtO
O
29
O
PO(OEt)2
CH2SBu
Ph3P
OEt
ꢀ
Ph3P=O
2-Butylthiomethyl-3-furoyl phosphonate 29 reacted
with acetylmethylene- 32 and ethoxycarbonylmethylene-
triphenylphosphorane 36 under the above-described con-
O
38
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1610
PEVZNER, SOKOLOVA
Scheme 12.
O
(EtO)2OP
XH
O
Ph3P
2C
XH
2C
Y
PO(OEt)2
Y
O
O
O
ꢀ43
39
4, 12, 27
Y = Me, OEt; X = Cl (4), NCS (12), BuS (27); X = Cl, Y = Me (39), OEt (40); X = NCS, Y = Me (41); X = BuS, Y= Me (42),
OEt (43).
Scheme 13.
HN
O
OP
(EtO)2
O
N
Y
O
(EtO)2OP
XH
O
2C
Y
44, 45
O
O
(EtO)2OP
39, 40
N3
NaN3
KI
Y
O
O
46
X = Me (39, 44, 46), OEt (40, 45).
obtained in 85 and 55% yield, respectively (Scheme 13).
Lower yield of ester 45 as compared to ketone 44 could
be due to its partial hydrolysis during isolation.
course of the Arbuzov reaction in the case of functional-
ized furoyl chlorides as well as the Wittig reaction in the
case of furoyl phosphonates. It is found that in the case
of 2-chloromethyl-3-furoyl chloride theArbuzov reaction
was accompanied by the shift of the halogen from the side
chain to the position 4 of the furan ring. It was established
that hydrochlorides of N-morpholinomethylfuroyl chlo-
rides showed dual reactivity in the reaction with triethyl
phosphite. 2,3-Disubstituted furans formed mixed anhy-
drides of phosphorous and carboxylic acid which were
further oxidized into the derivatives of phosphoric acid,
but 3,4-disubstituted isomer formed furoyl phosphonate.
The presence of sulfide group in the side chain did not
affect the course of the Arbuzov reaction.
Chloromethylketophosphonate 39 was also introduced
in the reaction with sodium azide. Considering that ther-
mal lability of furoyl phosphonate 13 did not permit its
use in the Wittig reaction, the above-mentioned process
was the only approach to the corresponding unsaturated
azidomethylfurylphosphonates. As before, the reaction
was carried out at the chloride : azide : potassium iodide
molar ratio of 1 : 2 : 0.1. In was found that the reaction
product was decomposed in acetonitrile at 80°C, but the
substitution proceeded smoothly in acetone at 20°C and
was complete in a week. The phosphorylated azidoketone
46 was isolated in 95% yield (Scheme 13). The signal of
the azidomethyl group protons in its NMR spectrum was
observed at 4.18 ppm, and the signal of the corresponding
carbon atom was found at 44.82 ppm.
Azidomethyl and thiocyanatomethyl groups might
decrease thermal stability of furoyl phosphonates as
well as of phosphorylated alkenes, which prevented the
use of the Wittig reaction for the preparation of certain
representatives of such furylalkenes. An alternative
approach to those substances was using the analogous
Hence, the presence of the adjacent group in the furan
ring of furoyl phosphonates significantly influenced the
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SYNTHESIS AND SELECTED REACTIONS OF 2(3)-FUROYL PHOSPHONATES
1611
chloromethyl derivatives in nucleophilic substitution
reactions. In certain cases, they proceeded smoothly only
at room temperature in polar aprotic solvents, the duration
being prolonged.
Н5-furan). 13С NMR spectrum (CDCl3), δС, ppm: 51.67
(СН3О), 52.98 (NСН2-furan), 53.50 (NСН2-morpholine),
66.94 (ОСН2-morpholine), 113.94 (С4-furan), 131.96
(С3-furan), 140.59 (С5-furan), 145.14 (С2-furan), 159.60
(С=О).
EXPERIMENTAL
Ethyl 2-(N-morpholinomethyl)-3-furoate was ob-
tained from ethyl 2-bromomethyl-3-furoate. Yield 87%,
light yellow oil. 1H NMR spectrum (CDCl3), δ, ppm: 1.33
t (3Н, СН3, JНН = 7.2 Hz), 2.52 t (4Н, NСН2-morpholine,
1H, 13C, 31P, and 15N NMR spectra were recorded us-
ing a Bruker AVANCE-400 spectrometer [400.13 MHz
(1Н), 100.16 MHz (13C), 161.67 МHz (31P), and
40.54 MHz (15N)]. IR spectra were recorded using a
Shimadzu IR Tracer 100 spectrometer with a DCIR
Specas adapter (diamond window). High-resolution
mass spectra were measured using a Bruker MicrOTOF
mass spectrometer. Melting points were measured using
a Boёtius apparatus.
JНН = 4.4 Hz), 3.68 t (4Н, ОСН2-morpholine, JНН
4.4 Hz), 3.91 s (2Н, NСН2-furan), 4.27 q (2Н, СН2О,
НН = 7.2 Hz), 6.66 d (1Н, Н4-furan, JНН = 2.0 Hz), 7.33
=
J
d (1Н, Н5-furan, JНН = 2.0 Hz). 13С NMR spectrum
(CDCl3), δС, ppm: 14.29 (СН3-ester), 46.33 (NСН2-
furan), 53.54 (NСН2-morpholine), 60.33 (СН2О-ester),
66.64 (ОСН2-morpholine), 110.69 (С4-furan), 116.73
(С3-furan), 141.80 (С5-furan), 157.06 (С2-furan), 163.60
(С=О).
2-Methyl-5-chloro-3-furoyl chloride (8). 0.4 mL
of thionyl chloride and 1 drop of DMF were added to a
suspension of 0.90 g of 2-methyl-5-chloro-3-furoic acid
in 10 mLof benzene. The formed mixture was refluxed for
8 h, the volatile products were distilled off, and the residue
was distilled in vacuum. Yield 0.20 g (20%), colorless
oil, bp 69°C (1 mmHg). 1H NMR spectrum (CDCl3), δ,
ppm: 2.60 s (3Н, СН3-furan), 6.56 s (1Н, Н4-furan). 13С
NMR spectrum (CDCl3), δС, ppm: 14.30 (СН3-furan),
108.34 (С4-furan), 120.25 (С3-furan), 135.88 (С5-furan),
160.82 (С2-furan), 161.03 (С=О).
Ethyl 4-(N-morpholinomethyl)-3-furoate was ob-
tained from ethyl 4-chloromethyl-3-furoate. Yield 65%,
light brown oil. 1H NMR spectrum (CDCl3), δ, ppm: 1.32
t (3Н, СН3, JНН = 7.2 Hz), 2.50 t (4Н, NСН2-morpholine,
JНН = 4.4 Hz), 3.62 s (2Н, NСН2-furan), 3.68 t (4Н,
ОСН2-morpholine, JНН = 4.4 Hz), 4.27 q (2Н, СН2О,
JНН = 7.2 Hz), 7.35 br. s (1Н, Н5-furan), 7.90 d (1Н,
Н2-furan, JНН = 1.2 Hz). 13С NMR spectrum (CDCl3),
δС, ppm: 14.30 (СН3-ester), 52.03 (NСН2-furan), 53.52
(NСН2-morpholine), 60.20 (СН2О-ester), 67.01 (ОСН2-
morpholine), 118.34 (С3-furan), 121.53 (С4-furan),
142.46 (С5-furan), 148.83 (С2-furan), 163.41 (С=О).
Synthesis of (N-morpholino)methyl derivatives
of alkyl furoates (general procedure). 25 mmol of
morpholine was added with stirring to a solution of
10 mmol of alkyl halomethylfuroate in 40 mLof benzene.
When the chloride was consumed, the reaction mixture
was refluxed for 8 h with stirring. The bromomethyl
compounds reacted within 10 h at room temperature.
After the reaction was complete, the obtained mixture
was extracted with 10% hydrochloric acid (3×10 mL),
aqueous extract was washed with 7 mL of ethyl acetate
and then treated with sodium carbonate under vigorous
stirring to pH 9–10. The formed oil was extracted with
chloroform (3×15 mL), the extract was washed with
10 mLof brine and dried over sodium sulfate. Chloroform
was distilled off, and the residue was kept in vacuum
(1 mmHg) at room temperature.
Hydrolysis of alkyl (N-morpholinomethyl)furoates
(general procedure). 15 mol of anhydrous potassium
hydroxide was added to a solution of 10 mmol of (N-
morpholinomethyl)furoate in 50 mL of ethanol. The
formed mixture was refluxed for 8 h with stirring, satu-
rated solution of hydrogen chloride in ethanol containing
25 mmol of hydrogen chloride was added, and the mixture
was stirred for 30 min. Potassium chloride was filtered
off and washed with 20 mL of ethanol. The obtained
ethanolic solution was evaporated to dryness, and the
residue was triturated with a solvent specified below for
each substance. The obtained crystals were filtered off
and dried in air to constant mass.
Methyl 3-(N-morpholinomethyl)2-furoate (18) was
obtained from methyl 3-bromomethyl-2-furoate. Yield
62%, light brown oil. H NMR spectrum (CDCl3), δ,
ppm: 2.46 br. s (4Н, NСН2-morpholine), 3.68 br. s (4Н,
ОСН2-morpholine), 3.73 s (2Н, NСН2-furan), 3.89 s
(3Н, СН3О), 6.58 br. s (1Н, Н4-furan), 7.47 br. s (1Н,
3-(N-Morpholinomethyl)-2-furoic acid hydrochlo-
ride (19) was crystallizes from 1 : 1 acetone–ethyl acetate.
Yield 93%. Decomposes at 200°C. H NMR spectrum
1
1
(DMSO-d6) δ, ppm: 3.06 br. t (4Н, NСН2-morpholine,
JНН = 4.4 Hz), 3.13 br. t (4Н, ОСН2-morpholine, JНН =
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 8 2019

1612
PEVZNER, SOKOLOVA
4.4 Hz), 4.51 s (2Н, NСН2-furan), 7.18 d (1Н, Н4-furan,
JНН = 2.0 Hz), 7.98 d (1Н, Н5-furan JНН = 2.0 Hz), 11.95
br. s (1Н, ОН). 13С NMR spectrum (DMSO-d6), δС,
ppm: 50.29 (NСН2-furan), 51.32 (NСН2-morpholine),
63.40 (ОСН2-morpholine), 115.46 (С4-furan), 122.12
(С3-furan), 143.82 (С5-furan), 146.68(С2-furan), 159.97
(С=О).
4-(N-Morpholinomethyl)-3-furoyl chloride hy-
drochloride (16). Yield 97%, white crystals, mp 182°C
(hexane).
Synthesis of butylthiomethyl derivatives of alkyl
furoates (general procedure). 11 mmol of butanethiol
and 22 mmol of anhydrous potassium carbonate were
added to a solution of 10 mmol of halomethylfuroate in
40 mL of acetonitrile. The reaction mixture was stirred
at 30–40°C for 3–4 h until complete liberation of carbon
dioxide. Inorganic salts were filtered off and washed with
10 mL of acetonitrile. The formed solution was evapo-
rated, the residue was dissolved in 30 mL of chloroform
and washed with 20 mLof water and 20 mLof brine.After
drying over calcium chloride, chloroform was distilled
off, and the residue was kept in vacuum (1 mmHg) for 1
h at room temperature.
2-(N-Morpholinomethyl)-3-furoic acid hydrochlo-
ride was crystallized from 2 : 1 acetone–ethyl acetate.
1
Yield 67%. Decomposes at 185°C. H NMR spectrum
(DMSO-d6) δ, ppm: 3.20 br. s (4Н, NСН2-morpholine),
3.83 br. s (4Н, ОСН2-morpholine), 4.64 s (2Н, NСН2-
furan), 6.83 d (1Н, Н4-furan, JНН = 2.0 Hz), 7.93 d (1Н,
Н5-furan JНН = 2.0 Hz), 9.73 br. s (1Н, ОН). 13С NMR
spectrum (DMSO-d6), δС, ppm: 42.97 (NСН2-furan),
51.36 (NСН2-morpholine), 63.53 (ОСН2-morpholine),
111.92 (С4-furan), 121.50 (С3-furan), 145.67 (С5-furan),
148.48(С2-furan), 164.04 (С=О).
Ethyl 4-(butylthiomethyl)-3-furoate (25) was ob-
tained from ethyl 4-chloromethyl-3-furoate. Yield 84%,
1
light yellow oil. H NMR spectrum (CDCl3), δ, ppm:
4-(N-Morpholinomethyl)-3-furoic acid hydrochlo-
ride was crystallized from ethyl acetate. Yield 95%.
Decomposes above 250°C. 1H NMR spectrum (DMSO-
d6) δ, ppm: 3.09 br. s (4Н, NСН2-morpholine), 3.90 br. s
(4Н, ОСН2-morpholine), 4.40 s (2Н, NСН2-furan), 8.14
d (1Н, Н5-furan, JНН = 1.6 Hz), 8.42 d (1Н, Н2-furan,
JНН = 1.6 Hz), 11.44 br. s (1Н, ОН). 13С NMR spec-
trum (DMSO-d6), δС, ppm: 48.58 (NСН2-furan), 51.05
(NСН2-morpholine), 63.15 (ОСН2-morpholine), 113.77
(С4-furan), 119.05 (С3-furan), 147.48 (С5-furan), 150.23
(С2-furan), 164.57 (С=О).
0.91 t (3Н, С4Н3-butyl, JНН = 7.2 Hz), 1.34 t (3Н, СН3,
JНН = 7.2 Hz), 1.40 sextet (2Н, С3Н2-butyl, JНН = 7.2 Hz,
1.57 quintet (2Н, С2Н2-butyl, JНН = 7.2 Hz), 2.50 t (2Н,
С1Н2S-butyl, JНН = 7.2 Hz), 3.78 s (2Н, furan-СН2S),
4.31 q (2Н, СН2О, JНН = 7.2 Hz), 7.39 d (1Н, Н5-furan,
JНН = 1.6 Hz), 7.98 d (1Н, Н2-furan, JНН = 1.6 Hz). 13С
NMR spectrum (CDCl3), δС, ppm: 13.67 (С4Н3-butyl),
14.27 (СН3-ester), 22.01 (С3Н2-butyl), 24.98 (С1Н2S-
butyl), 31.42 (С2Н2-butyl), 31.68 (furan-СН2S), 60.30
(СН2О), 117.50 (С4-furan), 122.81 (С3-futan), 141.95
(С5-furan), 149.09 (С2-furan), 163.22 (С=О).
Synthesis of (N-morpholinomethyl)furoyl chlorides
hydrochlorides (general procedure). Hydrochloride
of the corresponding (N-morpholinomethyl)furoic acid
(10 mmol) was suspended in 30 mL of thionyl chloride.
The obtained mixture was refluxed with vigorous stirring
for 8 h.After removal of thionyl chloride, the residue was
triturated with hexane. The formed crystals were filtered
off, washed with hexane, and kept in vacuum (1 mmHg)
for 20 min at room temperature. The obtained compounds
were completely hydrolyzed with residual moisture while
dissolution in DMSO. Due to that, their spectral data were
identical to those of corresponding acid hydrochlorides.
Ethyl 2-(butylthiomethyl)-3-furoate was obtained
from ethyl 2-bromomethyl-3-furoate. Yield 98%, light
1
yellow oil. H NMR spectrum (CDCl3), δ, ppm: 0.90 t
(3Н, С4Н3-butyl, JНН = 7.2 Hz), 1.36 t (3Н, СН3, JНН
=
7.2 Hz), 1.38 sextet (2Н, С3Н2-butyl, JНН = 7.2 Hz),
1.56 quintet (2Н, С2Н2-butyl, JНН = 7.2 Hz), 2.55 t (2Н,
С1Н2S-butyl, JНН = 7.2 Hz), 4.08 s (2Н, furan-СН2S),
4.31 q (2Н, СН2О, JНН = 7.2 Hz), 6.68 d (1Н, Н4-furan,
JНН = 1.8 Hz), 7.32 d (1Н, Н5-furan, JНН = 1.8 Hz). 13С
NMR spectrum (CDCl3), δС, ppm: 13.62 (С4Н3-butyl),
14.32 (СН3-ester), 21.96 (С3Н2-butyl), 27.06 (С1Н2S-
butyl), 31.47 (С2Н2-butyl), 31.72 (furan-СН2S), 60.41
(СН2О), 110.86 (С4-furan), 114.51 (С3-furan), 141.39
(С5-furan), 158.74 (С2-furan), 163.53 (С=О).
3-(N-Morpholinomethyl)-2-furoyl chloride hydro-
chloride (14). Yield 88%, mp 165°C (ethyl acetate–hex-
ane 1 : 3).
Methyl 3-(butylthiomethyl)-2-furoate was obtained
from methyl 3-bromomethyl-2-furoate; the residue after
distillation of chloroform was distilled in a vacuum.
2-(N-Morpholinomethyl)-3-furoyl chloride hydro-
chloride (15). Yield 79%, light grey crystals, mp 146°C
(hexane).
1
Yield 70%, light yellow oil, bp 154°C (1 mmHg). H
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SYNTHESIS AND SELECTED REACTIONS OF 2(3)-FUROYL PHOSPHONATES
1613
NMR spectrum (CDCl3), δ, ppm: 0.86 t (3Н, С4Н3-butyl,
JНН = 7.0 Hz), 1.36 sextet (2Н, С3Н2-butyl, JНН = 7.0 Hz),
1.54 quintet (2Н, С2Н2-butyl, JНН = 7.0 Hz), 2.44 t (2Н,
С1Н2S-butyl, JНН = 7.0 Hz), 3.90 s (3Н, СН3О), 3.92 s
(2Н, furan-СН2S), 6.58 br. s (1Н, Н4-furan), 7.47 br. s
(1Н, Н5-furan). 13С NMR spectrum (CDCl3), δС, ppm:
13.63 (С4Н3-butyl), 21.94 (С3Н2-butyl), 25.90 (С1Н2S-
butyl), 31.26 (С2Н2-butyl), 31.34 (furan-СН2S), 51.73
(СН3О), 113.95 (С4-furan), 132.99 (С3-furan), 140.08
(С5-furan), 145.29 (С2-furan), 159.59 (С=О).
(2Н, С3Н2-butyl, JНН = 7.0 Hz), 1.56 quintet (2Н, С2Н2-
butyl, JНН = 7.0 Hz), 2.65 t (2Н, С1Н2S-butyl, JНН
7.0 Hz), 3.94 s (2Н, furan-СН2S), 6.64 d (1Н, Н4-furan,
НН = 7.0 Hz), 7.57 d (1Н, Н5-furan, JНН = 7.0 Hz), 11.63
br. s (1Н, ОН). 13С NMR spectrum (CDCl3), δС, ppm:
13.64 (С4Н3-butyl), 21.96 (С3Н2-butyl), 25.94 (С1Н2S-
butyl), 31.32 (С2Н2-butyl), 31.32 (furan-СН2S), 114.41
(С4-furan), 135.48 (С3-furan), 139.36 (С5-furan), 146.58
(С2-furan), 164.31 (С=О).
=
J
Synthesis of (butylthiomethyl)furoyl chlorides
(general procedure). 13 mmol of thionyl chloride and
2 drops of DMF were added at vigorous stirring to a
solution of 10 mmol of (butylthiomethyl)furoic acid in
40 mL of benzene. The mixture was refluxed with stir-
ring for 8 h, volatile products were removed in vacuum,
and the residue was kept in vacuum (1 mmHg) for 1 h at
room temperature.
Alkaline hydrolysis of alkyl (butylthiomethyl)-
furoates (general procedure). 12 mmol of potassium
hydroxide was added to a solution of 10 mmol of alkyl
(butylthiomethyl)furoate in 50 mL of ethanol. The mix-
ture was refluxed for 8 h, and then ethanol was distilled
off. The residue was dissolved in 15 mL of water and
washed with 8 mL of ethyl acetate. The aqueous solu-
tion was acidified with concentrated hydrochloric acid to
pH 2–3 and extracted with chloroform (3×15 mL). The
extract was dried with sodium sulfate, chloroform was
removed, and the residue was kept in vacuum (1 mmHg)
for 1 h at room temperature.
4-(Butylthiomethyl)-3-furoyl chloride (23). Yield
1
96%, light yellow oil. H NMR spectrum (CDCl3), δ,
ppm: 0.93 t (3Н, С4Н3-butyl, JНН = 7.2 Hz), 1.42 sextet
(2Н, С3Н2-butyl, JНН = 7.2 Hz), 1.58 quintet (2Н, С2Н2-
butyl, JНН = 7.2 Hz), 2.52 t (2Н, С1Н2S-butyl, JНН
=
4-(Butylthiomethyl)-3-furoic acid (26). Yield 67%,
7.2 Hz), 3.79 s (2Н, furan-СН2S), 7.49 d (1Н, Н5-furan,
НН = 1.4 Hz), 8.23 d (1Н, Н2-furan, JНН = 1.4 Hz). 13С
1
light yellow crystals, mp 62-63°C. H NMR spectrum
J
(CDCl3), δ, ppm: 0.93 t (3Н, С4Н3-butyl, JНН = 7.2 Hz),
1.42 sextet (2Н, С3Н2-butyl, JHH = 7.2 Hz), 1.59 quintet
(2Н, С2Н2-butyl, JНН = Hz), 2.53 t (2Н, С1Н2S-butyl,
JНН = 7.2 Hz), 3.80 s (2Н, furan-СН2S), 7.44 (1Н, Н5-
furan), 8.11 (1Н, Н2-furan), 8.91 br. s (1Н. ОН). 13С NMR
spectrum (CDCl3), δС, ppm: 13.72 (С4Н3-butyl), 22.03
(С3Н2-butyl), 24.81 (С1Н2S-butyl), 31.40 (С2Н2-butyl),
31.71 (furan-СН2S), 117.22 (С3-furan), 122.98 (С4-furan),
142.37 (С5-furan), 150.65 (С2-furan), 168.73 (С=О).
NMR spectrum (CDCl3), δС, ppm: 13.67 (С4Н3-butyl),
21.97 (С3Н2-butyl), 24.70 (С1Н2S-butyl), 31.35 (С2Н2-
butyl), 31.87 (furan-СН2S), 123.06 (С4-furan), 128.34
(С3-furan), 143.36 (С5-furan), 154.47 (С2-furan), 159.18
(С=О).
2-(Butylthiomethyl)-3-furoyl chloride (28). Yield
1
89%, light yellow oil. H NMR spectrum (CDCl3), δ,
ppm: 0.91 t (3Н, С4Н3-butyl, JНН = 7.2 Hz), 1.39 sextet
(2Н, С3Н2-butyl, JНН = 7.2 Hz), 1.56 quintet (2Н, С2Н2-
2-(Butylthiomethyl)-3-furoic acid. Yield 69%, light
yellow crystals, mp 35°C. 1H NMR spectrum (CDCl3), δ,
ppm: 0.90 t (3Н, С4Н3-butyl, JНН = 7.2 Hz), 1.38 sextet
(2Н, С3Н2-butyl, JНН = 7.2 Hz), 1.57 quintet (2Н, С2Н2-
butyl, JНН = 7.2 Hz), 2.56 t (2Н, С1Н2S-butyl, JНН
=
7.2 Hz), 4.01 s (2Н, furan-СН2S), 6.81 d (1Н, Н4-furan,
НН = 2.0 Hz), 7.37 d (1Н, Н5-furan, JНН = 2.0 Hz). 13С
J
NMR spectrum (CDCl3), δС, ppm: 13.62 (С4Н3-butyl),
21.91 (С3Н2-butyl), 27.16 (С1Н2S-butyl), 31.35 (С2Н2-
butyl), 32.04 (furan-СН2S), 112.78 (С4-furan), 118.76
(С3-furan), 141.90 (С5-furan), 161.56 (С2-furan), 161.98
(С=О).
butyl, JНН = 7.2 Hz), 2.56 t (2Н, С1Н2S-butyl, JНН
=
7.2 Hz), 4.09 s (2Н, furan-СН2S), 6.72 br. s (1Н, Н4-
furan), 7.36 br. s (1Н, Н5-furan), 11.63 br. s (1Н, ОН).
13С NMR spectrum (CDCl3), δС, ppm: 13.62 (С4Н3-
butyl), 21.96 (С3Н2-butyl), 26.93 (С1Н2S-butyl), 31.48
(С2Н2-butyl), 31.78 (furan-СН2S), 111.02 (С4-furan),
113.69 (С3-furan), 141.75 (С5-furan), 160.56 (С2-furan),
169.48 (С=О).
Reaction of furoyl chlorides with triethyl phosphite
(general procedure). 10.5 mmol of triethyl phosphite
was added to a solution of 10 mmol of the correspond-
ing furoyl chloride in 30 mL of benzene. The reaction
mixture was stirred for 1–2 h and left overnight. On the
next day, benzene was distilled off, and the residue was
kept in vacuum (1 mmHg) for 1 h at room temperature.
3-(Butylthiomethyl)-2-furoic acid. Yield 71%, light
yellow crystals, mp 40°C. 1H NMR spectrum (CDCl3), δ,
ppm: 0.88 t (3Н, С4Н3-butyl, JНН = 7.0 Hz), 1.37 sextet
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 8 2019

1614
PEVZNER, SOKOLOVA
1
14.5 Hz), 193.12 d (С=О, JРС = 184.1 Hz). 31Р NMR
Diethyl 3-chloromethyl-2-furoyl phosphonate (2).
Yield 96%, light brown oil. 1H NMR spectrum (CDCl3),
δ, ppm: 1.39 t (6Н, СН3, JНН = 7.2 Hz), 4.32 d. q (4Н,
СН2ОР, JНН = 7.2 Hz, JРН = 14.8 Hz), 4.75 s (1Н,
СН2Cl), 4.82 s (1Н, СН2Cl), 6.78 br. s (0.5 Н, Н4-furan),
6.80 d (0.5 Н, Н4-furan, JНН = 2.6 Hz), 7.66 br. s (1Н,
Н5-furan). 13С NMR spectrum (CDCl3), δС, ppm: 16.39
spectrum (CDCl
found 303.0160, calculated for С10Н14ClО5Р 303.0167
[M + Na]+.
3), δР, ppm: –2.31. Mass spectrum, m/z:
Diethyl 4-(butylthiomethyl)-3-furoyl phospho-
nate (27). Yield 96%, yellow syrup. 1H NMR spectrum
(CDCl3), δ, ppm: 0.89 t (3Н, С4Н3-butyl, JНН = 7.2 Hz),
1.31–1.41 m (8Н, СН3-phosphonate + С3Н2-butyl),
1.55 quintet (2Н, С2Н2-butyl, JНН = 7.2 Hz), 2.49 t (2Н,
С1Н2S-butyl, JНН = 7.2 Hz), 3.78 s (2Н, furan-СН2S),
4.23 d. q (4Н, СН2ОР, JНН = 7.2 Hz, JРН = 15.2 Hz), 7.22
d (1Н, Н2-furan, JРН = 1.6 Hz), 7.43 s (1Н, Н5-furan). 13С
NMR spectrum (CDCl3), δС, ppm: 13.66 (С4Н3-butyl),
16.35 d (СН3-phosphonate, 2JРС = 5.6 Hz), 21.96 (С3Н2-
butyl), 25.21 (С1Н2S-butyl), 31.42 (С2Н2-butyl), 31.79
(furan-СН2S), 64.07 d (СН2ОР, JРС = 6.9 Hz), 122.37
d (С4-furan, 3JРС = 11.1 Hz), 125.05 d (С3-furan, 2JРС
69.4 Hz), 142.31 d (С5-furan, JРС = 1.1 Hz), 155.43 d
(С2-furan, 3JРС = 4.1 Hz), 194.02 d (С=О, 1JРС = 179.4
Hz). 31Р NMR spectrum (CDCl3), δР, ppm: –3.40.
2
d (СН3-phosphonate, JРС = 5.8 Hz), 35.90 (СН2Cl),
36.36 (СН2Cl), 64.28 d (СН2ОР, 2JРС = 7.1Hz), 115.43
3
(С4-furan), 134.19 d (С3-furan, JРС = 8.7 Hz), 147.42
d (С2-furan, 2JРС = 60.1 Hz), 147.45 d (С2-furan, 2JРС
=
60.1 Hz), 147.79 (С5-furan), 148.21 (С5-furan), 187.38
d (С=О, 1JРС = 187.6 Hz). 31Р NMR spectrum (CDCl3),
δР, ppm: –2.31.
Diethyl 4-chloromethyl-3-furoyl phosphonate (4).
Yield 98%, light brown oil. 1H NMR spectrum (CDCl3),
δ, ppm: 1.38 t (6Н, СН3, JНН = 7.2 Hz), 4.21–4.29 m (4Н,
СН2ОР ), 4.72 br. s (2Н, СН2Cl), 7.56 d. t (1Н, Н5-furan,
2
=
3
J
РН = 2.8 Hz, JНН = 1.4 Hz), 8.79 d (1Н, Н2-furan, JРН
=
1.6 Hz). 13С NMR spectrum (CDCl3), δС, ppm: 16.36 d
(СН3-phosphonate, 2JРС = 5.7 Hz), 36.26 (СН2Cl), 64.27
Diethyl 2-(butylthiomethyl)-3-furoyl phospho-
nate (27). Yield 95%, yellow syrup. 1H NMR spectrum
(CDCl3), δ, ppm: 0.90 t (1.5Н, С4Н3-butyl, JНН = 7.2 Hz),
0.91 t (1.5Н, С4Н3-butyl, JНН = 7.2 Hz), 1.34 t (3Н, СН3,
JНН = 7.2 Hz), 1.39 t (3Н, СН3, JНН = 7.2 Hz), 1.35–1.41
d (СН2ОР, JРС = 7.1 Hz), 122.15 d (С4-furan, 3JРС
=
2
10.8 Hz), 124.66 d (С3-furan, JРС = 69.8 Hz), 143.28
2
(С5-furan), 155.34 d (С2-furan, JРС = 4.1 Hz), 194.10
3
d (С=О, 1JРС = 181.6 Hz). 31Р NMR spectrum (CDCl3),
δР, ppm: –3.69.
m (2Н, С3Н2-butyl), 1.55 quintet (1Н, С2Н2-butyl, JНН
=
Diethyl 2-methyl-5-chloro-3-furoyl phosphonate
(6). Yield 96%, light brown oil. H NMR spectrum
(CDCl3), δ, ppm: 1.41 t (6Н, СН3, JНН = 7.0 Hz),
7.2 Hz), 1.56 quintet (1Н, С2Н2-butyl, JНН = 7.2 Hz), 2.54
t (1Н, С1Н2S-butyl, JНН = 7.2 Hz), 2.56 t (1Н, С1Н2S-
butyl, JНН = 7.2 Hz), 4.00 s (1Н, furan-СН2S), 4.01 s (1Н,
1
2.55 s (3Н, СН3-furan), 4.27 d. q (4Н, СН2ОР, JНН
=
furan-СН2S), 4.26 d. q (4Н, СН2ОР, JНН = 7.2 Hz, JРН =
7.0 Hz, JРН = 14.8 Hz), 6.95 s (1Н, Н4-furan). 13С NMR
spectrum (CDCl3), δС, ppm: 14.59 (СН3-furan), 16.34
14.4 Hz), 6.80 d (1Н, Н4-furan, JРН = 2.0 Hz), 7.21 d (1Н,
Н5-furan, JРН = 2.0 Hz). 13С NMR spectrum (CDCl3), δС,
ppm: 13.61 (С4Н3-butyl), 16.40 d (СН3-phosphonate,
2JРС = 5.7 Hz), 21.90 (С3Н2-butyl), 21.92 (С3Н2-butyl),
27.14 (С1Н2S-butyl), 27.61 (С1Н2S-butyl), 31.34
(С2Н2-butyl), 31.44 (С2Н2-butyl), 31.93 (furan-СН2S),
2
d (СН3-phosphonate, JРС = 5.6 Hz), 64.05 d (СН2ОР,
2JРС = 7.1 Hz), 107.16 d (С4-furan,3JРС = 2.0 Hz), 122.06
d (С3-furan, 2JРС = 68.8 Hz), 135.57 (С5-furan), 160.36 d
(С2-furan,3JРС =14.5Hz),193.25d(С=О,1JРС =184.2Hz).
31Р NMR spectrum (CDCl3), δР, ppm: –2.18.
2
32.03 (furan-СН2S), 63.95 d (СН2ОР, JРС = 7.1 Hz),
111.41 d (С4-furan, 3JРС = 2.6 Hz), 120.54 d (С3-furan,
2JРС = 68.6 Hz), 141.86 (С5-furan), 160.40 d (С2-furan,
Diethyl 2-methyl-4-chloro-3-furoyl phosphonate
(9). The residue after removal of solvents was distilled
in vacuum. Fraction with bp 144–146°C (1 mmHg) was
collected, yield 37%, colorless oil. 1H NMR spectrum
(CDCl3), δ, ppm: 1.32 t (6Н, СН3, JНН = 7.0 Hz), 2.59
s (3Н, СН3-furan), 4.10 d. q (4Н, СН2ОР, JНН = 7.0 Hz,
1
3JРС = 9.0 Hz), 193.94 d (С=О, JРС = 183.5 Hz). 31Р
NMR spectrum (CDCl3), δР, ppm: –2.09.
Reaction of (N-morpholinomethyl)furoyl chlorides
hydrochlorides with triethyl phosphite (general pro-
cedure). 11 mmol of triethylamine was added with stir-
ring at room temperature to a suspension of 10 mmol of
hydrochloride 14–16 in 30 mL of benzene. The reaction
mixture was stirred for 20 min at room temperature, and
then 10.2 mmol of triethyl phosphite was added. The
J
РН = 14.8 Hz), 7.06 s (1Н, Н5-furan). 13С NMR spectrum
(CDCl3), δС, ppm: 14.74 (СН3-furan), 16.36 d (СН3-
2
2
phosphonate, JРС = 5.7 Hz), 64.07 d (СН2ОР, JРС
=
=
=
7.2 Hz), 121.16 (С4-furan), 122.63 d (С3-furan, JРС
68.7 Hz), 142.75 (С5-furan), 162.54 d (С2-furan, 3JРС
2
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 8 2019

SYNTHESIS AND SELECTED REACTIONS OF 2(3)-FUROYL PHOSPHONATES
1615
mixture was stirred for 3–4 h and left overnight. On the
next day, triethylamine hydrochloride was filtered off,
the filtrate was evaporated, and the residue was kept in a
vacuum (1 mmHg) for 1 h at room temperature.
potassium thiocyanate and 1 mmol of potassium iodide
were added at room temperature at vigorous stirring to a
solution of 10 mmol of chloromethylfuroyl phosphonate
2,4 in 30 mL of acetonitrile. The reaction mixture was
stirred at room temperature for 24 h, the precipitate was
filtered off, and the filtrate was evaporated. The residue
was dissolved in 30 mL of chloroform, washed with
10 mLof water and 10 mLof brine, and dried over sodium
sulfate. After removal of chloroform, the residue was
kept in vacuum (1 mmHg) for 1 h at room temperature.
Mixed anhydride of 3-(N-morpholinomethyl)-2-fu-
roic and diethylphosphoric acids (20). Yield 78%, light
brown oil.1H NMR spectrum (CDCl3), δ, ppm: 1.30 t (6Н,
СН3, JНН = 7.0 Hz), 2.53 br. s (4Н, NСН2-morpholine),
3.71 br. s (4Н, ОСН2-morpholine), 3.84 s (2Н, NСН2-
furan), 4.08 d. q (4Н, СН2ОР, JНН = 7.0 Hz, JРН = 15.2 Hz),
6.76 br. s (1Н, Н4-furan), 7.42 br. s (1Н, Н5-furan).
13С NMR spectrum (CDCl3), δС, ppm: 16.10 d (СН3-
phosphonate, 2JРС = 6.7 Hz), 53.31 (NСН2-furan), 53.39
Diethyl 3-(thiocyanatomethyl)-2-furoyl phospho-
nate (10). Yield 83%, light brown oil.1H NMR spectrum
(CDCl3), δ, ppm: 1.28–1.38 m (6Н, СН3), 4.29 d. q (4Н,
СН2ОР, JНН = 7.0 Hz, JРН = 14.8 Hz), 4.29 s (2Н, СН2S),
6.76 d (1Н, Н4-furan, JНН = 1.6 Hz), 7.70 d (1Н, Н5-
furan, JНН = 1.6 Hz). 13С NMR spectrum (CDCl3), δС,
ppm: 16.39 d (СН3-phosphonate, 2JРС = 5.7 Hz), 28.27
(СН2S), 64.66 d (СН2ОР, 2JРС = 7.2 Hz), 111.67 (SCN),
114.69 d (С4-furan, 4JРС = 1.3 Hz), 131.40 d (С3-furan,
3JРС = 8.4 Hz), 148.07 (С5-furan), 148.19 d (С2-furan,
2
(NСН2-morpholine), 63.58 d (СН2ОР, JРС = 5.8 Hz),
66.63 (ОСН2-morpholine), 115.11 (С4-furan), 128.28
(С3-furan), 143.83 (С5-furan), 147.10 (С2-furan), 153.51
(С=О). 31Р NMR spectrum (CDCl3), δР, ppm: -0.98.
Mixed anhydride of 2-(N-morpholinomethyl)-
3-furoic and diethylphosphorous acids (21). Yield 65%,
light brown oil.1H NMR spectrum (CDCl3), δ, ppm: 1.28
t (6Н, СН3, JНН = 7.2 Hz), 2.57 t (4Н, NСН2-morpholine,
1
2JРС = 59.6 Hz), 187.38 d (С=О, JРС = 188.0 Hz). 31Р
JНН = 4.4 Hz), 3.71 t (4Н, ОСН2-morpholine, JНН
4.4 Hz), 3.86 d. q (4Н, СН2ОР, JНН = 7.2 Hz, JРН
=
=
NMR spectrum (CDCl3), δР, ppm:–2.68.
Diethyl 4-(thiocyanatomethyl)-3-furoyl phospho-
nate (12). Yield 99%, light brown oil.1H NMR spectrum
(CDCl3), δ, ppm: 1.37 t (6Н, СН3, JНН = 7.2 Hz), 4.19 s
(2Н, СН2S), 4.21–4.28 m (4Н, СН2ОР), 7.60 s (1Н, Н5-
furan), 8.82 (1Н, Н2-furan). 13С NMR spectrum (CDCl3),
δС, ppm: 16.34 d (СН3-phosphonate, 2JРС = 5.7 Hz), 28.14
(СН2S), 64.36 d (СН2ОР, 2JРС = 7.1 Hz), 112.29 (SCN),
118.99 d (С4-furan, 3JРС = 10.8 Hz), 123.88 d (С3-furan,
2JРС = 68.5 Hz), 143.24 (С5-furan), 155.77 d (С2-furan,
14.8 Hz), 3.98 s (2Н, NСН2-furan), 6.74 d (1Н, Н4-furan,
JНН = 2.0 Hz), 7.44 d (1Н, Н5-furan, JНН = 2.0 Hz).
13С NMR spectrum (CDCl3), δС, ppm: 16.90 d (СН3-
phosphonate, 2JРС = 5.0 Hz), 53.25 (NСН2-morpholine),
53.34 (NСН2-furan), 57.99 d (СН2ОР, 2JРС = 11.9 Hz),
66.76 (ОСН2-morpholine), 110.55 (С4-furan), 115.47
(С3-furan), 142.52 (С5-furan), 158.50 (С2-furan), 160.54
(С=О). 31Р NMR spectrum (CDCl3), δР, ppm: 138.75.
Diethyl 4-(N-morpholinomethyl)-3-furoyl phos-
phonate (22). Yield 86%, light brown syrup. 1H NMR
1
3JРС = 4.0 Hz), 194.71 d (С=О, JРС = 183.0 Hz). 31Р
NMR spectrum (CDCl3), δР, ppm:–3.22.
spectrum (CDCl3), δ, ppm: 1.33 t (6Н, СН3, JНН
=
7.2 Hz), 2.51 br. s (4Н, NСН2-morpholine), 3.64 br. s
(2Н, NСН2-furan), 3.69 br. s (4Н, ОСН2-morpholine),
4.10 d. q (4Н, СН2ОР, JНН = 7.2 Hz, JРН = 14.4 Hz),
7.44 s (1Н, Н5-furan), 8.14 d (1Н, Н5-furan). 13С NMR
spectrum (CDCl3), δС, ppm: 16.36 d (СН3-phosphonate,
2JРС = 5.5 Hz), 51.70 (NСН2-furan), 53.48 (NСН2-
morpholine), 53.54 (NСН2-morpholine), 63.61 d (СН2ОР,
2JРС = 5.8 Hz), 66.94 (ОСН2-morpholine), 67.02 (ОСН2-
morpholine), 121.33 (С4-furan), 125.59 d (С3-furan, 2JРС =
Reaction of furoyl phosphonate 2 with sodium
azide. 0.43 g (6.6 mmol) of sodium azide and 0.05 g
(0.3 mmol) of potassium iodide were added with stirring
to a solution of 0.93 g (3.3 mmol) of furoyl phosphonate
2 in 15 mL of acetone. The mixture was stirred at room
temperature for a week, the inorganic salts were filtered
off, and the filtrate was evaporated. The residue was dis-
solved in 20 mLof chloroform, the obtained solution was
washed with 5 mL of water and 5 mL of brine, and dried
over sodium sulfate. Chloroform was removed, and the
residue was kept in vacuum (1 mmHg) for 1 h at room
temperature. Light brown oil, 1.10 g, was obtained. It
consisted of 3-(azidomethyl)-2-furoyl azide and diethyl
hydrogen phosphite. According to 1H NMR data, molar
69.4 Hz), 142.69 (С5-furan), 155.24 d (С2-furan, 3JРС
=
1
4.1 Hz), 194.06 d (С=О, JРС = 179.5 Hz). 31Р NMR
spectrum (CDCl3), δР, ppm: –3.19.
Reaction of chloromethylfuroyl phosphonates with
potassium thiocyanate (general procedure). 20 mmol of
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 8 2019

1616
PEVZNER, SOKOLOVA
ratio of components was 1 : 0.6. Calculated yield of furoyl
azide 11 70%.
off, and the residue was kept in vacuum (1 mmHg) during
1 h at room temperature.
Diethyl hydrogen phosphite. 1H NMR spectrum
(CDCl3), δ, ppm: 1.32 t (6Н, СН3, JНН = 7.2 Hz), 4.29
d. q (4Н, СН2ОР, JНН = 7.2 Hz, JРН = 16.0 Hz), 6.80 d
(Р-Н, JРН = 692.8 Hz). 31Р NMR spectrum (CDCl3), δР,
ppm: 7.35.
4-(3-Chloromethylfur-2-yl)-4-(diethoxyphos-
phoryl)-but-3-ene-2-one (33) was prepared from furoyl
phosphonate 2. Yield 61%, light brown syrup. 1H NMR
spectrum (CDCl3), δ, ppm: 1.28–1.37 m (6Н, СН3-
phosphonate), 2.05 s (3Н, СН3-ketone), 4.07–4.18 m (4Н,
СН2О-phosphonate), 4.49 s (2Н, CH2Cl), 6.57 br. s (1Н,
Н4-furan), 7.13 d (1Н, =СН, JРН = 22.0 Hz), 7.52 br. s
(1Н, Н5-furan). 13С NMR spectrum (CDCl3), δС, ppm:
3-(Azidomethyl)-2-furoyl azide (11). IR spectrum, ν,
сm–1: 2102 (N3 of azidomethyl group), 2141 (N3 of acyl
azide), 1687 (С=О). 1Н NMR spectrum (CDCl3), δ, ppm:
4.62 s (2Н, СН2N3), 6.65 br. s (1Н, Н4-furan), 7.54 br. s
(1Н, Н5-furan). 13С NMR spectrum (CDCl3), δС, ppm:
45.64 (СН2N3), 113.68 (С4-furan), 131.71 (С3-furan),
141.20 (С5-furan), 146.93 (С2-furan), 162.90 (С=О). 15N
NMR spectrum (CDCl3), δN, ppm: 249 (N1-azidomethyl),
73 (N3-azidomethyl).
2
16.26 d (СН3-phosphonate, JРС = 6.9 Hz), 29.68 br. s
2
(СН3-ketone), 37.05 (CH2Cl), 63.24 d (СН2ОР, JРС
=
5.9 Hz), 63.63 d (СН2ОР, 2JРС = 5.9 Hz), 112.98 d (С4-
furan, 4JРС = 1.5 Hz), 123.37 d (С3-furan, 3JРС = 5.7 Hz),
128.97 d (=СР, 1JРС = 179.0 Hz), 131.77 d (=СН, 2JРС
=
3.1 Hz), 143.95 d (С5-furan, 3JРС = 2.3 Hz), 144.54 d
3
(С2-furan, 3JРС = 7.3 Hz), 198.67 d (С=О, JРС = 20.2
Diethyl 4-(azidomethyl)-3-furoyl phosphonate
(13). 1.20 g (18.4 mmol) of sodium azide and 0.15 g (0.9
mmol) of potassium iodide were added with stirring to
a solution of 2.60 g (9.2 mmol) of furoyl phosphonate 4
in 25 mL of acetonitrile. The mixture was stirred for 48
h at room temperature and the formed precipitate was
filtered off. The filtrate was evaporated, the residue was
dissolved in 40 mL of chloroform, washed with 10 mL
of water and with 10 mL of brine, and dried over sodium
sulfate. Chloroform was removed, and the residue was
kept in vacuum (1 mmHg) for 1 h at room temperature.
Yield 2.33 g (8.1 mmol, 88%), light brown oil. 1H NMR
Hz). 31Р NMR (CDCl3), δР, ppm: 12.71.
4-(2-Butylthiomethylfur-3-yl)-4-(diethoxyphos-
phoryl)but-3-en-2-one (37) was prepared from furoyl
phosphonate 29. Yield 80%, yellowish brown syrup. 1H
NMR spectrum (CDCl3), δ, ppm: 0.85 t (3Н, С4Н3-butyl,
JНН = 7.2 Hz), 1.32 t (6Н, СН3, JНН = 7.2 Hz), 1.37 sextet
(2Н, С3Н2-butyl, JНН = 7.2 Hz), 1.55 quintet (2Н, С2Н2-
butyl, JНН = 7.2 Hz), 2.12 s (СН3-ketone), 2.59 t (2Н,
С1Н2S-butyl, JНН = 7.2 Hz), 3.63 s (2Н, furan-СН2S),
4.08–4.16 m (4Н, СН2ОР), 6.66 d (1Н, Н4-furan, JРН
=
2.0 Hz), 7.01 d (1Н, , =СН, JРН = 23.2 Hz), 7.33 d (1Н,
Н5-furan, JРН = 2.0 Hz). 13С NMR spectrum (CDCl3),
δС, ppm: 13.67 (С4Н3-butyl), 15.92 d (СН3-phosphonate,
2JРС = 7.5 Hz), 16.36 d (СН3-phosphonate, 2JРС = 6.1 Hz),
21.91 (С3Н2-butyl), 27.03 (С1Н2S-butyl), 30.45 (СН3-
ketone), 31.35 (С2Н2-butyl), 32.38 (furan-СН2S), 62.95
spectrum (CDCl3), δ, ppm: 1.36 t (6Н, СН3, JНН
=
7.2 Hz), 4.08–4.18 m (4Н, СН2ОР), 4.49 s (2Н, СН2N3),
7.49 s (1Н, Н5-furan), 8.80 s (1Н, Н2-furan). 13С NMR
spectrum (CDCl3), δС, ppm: 16.32 d (СН3-phosphonate,
2JРС = 5.6 Hz), 45.01 (СН2N3), 64.29 d (СН2ОР, 2JРС
=
2
3
d (СН2ОР, JРС = 6.2 Hz), 112.09 d (С4-furan, JРС
=
7.0 Hz), 119.66 d (С4-furan, 3JРС = 10.8 Hz), 124.81 d
2.6 Hz), 114.29 d (С3-furan, JРС = 8.2 Hz), 131.98 d
(=СН, 2JРС = 2.6 Hz), 132.64 d (=СР, 1JРС = 178.1 Hz),
141.94 (С5-furan), 150.90 d (С2-furan, 3JРС = 10.0 Hz),
2
2
(С3-furan, JРС = 69.4 Hz), 142.70 (С5-furan), 155.44
3
1
d (С2-furan, JРС = 4.5 Hz), 194.22 d (С=О, JРС
=
181.6 Hz). 31Р NMR spectrum (CDCl3), δР, ppm: –3.71.
199.56 d (С=О, JРС = 22.1 Hz). 31Р NMR spectrum
3
Reaction of furoyl phosphonates with resonance-
stabilized phosphoranes 32 and 36 (general procedure).
11 mmol of phosphorane 32 or 36 was added with stirring
to a solution of 10 mmol of furoyl phosphonate in 20 mL
of benzene. The mixture was refluxed with stirring for
9–10 h, the reaction progress was monitored by means
of 31P NMR spectroscopy. After disappearance of the
signal of phosphorus nucleus from furoyl phosphonate,
the reaction mixture was diluted with 75 mL of hexane,
stirred for 30 min, and left overnight. On the next day, the
solution was decanted, benzene and hexane were distilled
(CDCl3), δР, ppm: 14.77.
Ethyl 3-(2-butylthiomethylfur-3-yl)-3-(diethoxy-
phosphoryl)acrylate (38) was prepared from furoyl
phosphonate 29. Yield 86%, yellowish brown syrup. 1H
NMR spectrum (CDCl3), δ, ppm: 0.85 t (1.5Н, С4Н3-
butyl, JНН = 7.2 Hz), 0.91 t (1.5Н, С4Н3-butyl, JНН
=
7.2 Hz), 1.21 t (3Н, СН3-ester, JНН = 7.2 Hz), 1.33 t (6Н,
СН3, JНН = 7.2 Hz), 1.33–1.35 m (2Н, С3Н2-butyl), 1.48
quintet (1Н, С2Н2-butyl, JНН = 7.2 Hz), 1.55 quintet (1Н,
С2Н2-butyl, JНН = 7.2 Hz), 2.47 t (1Н, С1Н2S-butyl,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 8 2019

SYNTHESIS AND SELECTED REACTIONS OF 2(3)-FUROYL PHOSPHONATES
1617
JНН = 7.2 Hz), 2.55 t (1Н, С1Н2S-butyl, JНН = 7.2 Hz),
3.70 s (1Н, furan-СН2S), 3.74 q (1Н, СН2О-ester, JНН
7.2 Hz), 3.96 s (1Н, furan-СН2S), 3.99 q (1Н, СН2О-ester,
НН = 7.2 Hz), 4.09–4.20 m (4Н, СН2ОР), 6.37 d (0.5Н,
Н4-furan, JРН = 2.0 Hz), 6.68 d (0.5Н, Н4-furan, JРН
2.0 Hz), 6.89 d (1Н, , =СН, JРН = 22.4 Hz), 7.26 d (0.5Н,
Н5-furan, JРН = 2.0 Hz), 7.38 d (0.5Н, Н5-furan, JРН
7.9 Hz), 134.01 d (=СН, 2JРС = 11.1 Hz), 135.34 d (=СР,
1JРС = 179.0 Hz), 141.61 d (С2-furan, 3JРС = 6.1 Hz),
=
142.03 (С5-furan), 164.06 d (С=О, 3JРС = 28.1 Hz). 31
NMR spectrum (CDCl3), δР, ppm: 13.40.
Р
J
=
4-(4-Thiocyanatomethylfur-3-yl)-4-(diethoxyphos-
phoryl)but-3-en-2-one (41) was prepared from furoyl
=
1
phosphonate 12. Yield 54%, brown syrup. H NMR
2.0 Hz). 13С NMR spectrum (CDCl3), δС, ppm: 13.72
(С4Н3-butyl), 13.85 (С4Н3-butyl), 14.00 (СН3-ester),
14.69 (СН3-ester), 15.94 d (СН3-phosphonate, 2JРС = 7.4
spectrum (CDCl3), δ, ppm: 1.34 t (6Н, СН3-phosphonate,
JНН = 7.2 Hz), 2.20 s (3Н, СН3-ketone), 4.10–4.19 m
(4Н, СН2О-phosphonate), 4.14 s (2Н, CH2SCN), 7.09
d (1Н, , =СН, JРН = 22.8 Hz), 7.63 br. s (1Н, Н5-furan),
7.71 br. s (1Н, Н5-furan). 13С NMR spectrum (CDCl3),
2
Hz), 16.37 d (СН3-phosphonate, JРС = 6.3 Hz), 21.94
(С3Н2-butyl), 21.96 (С3Н2-butyl), 27.18 (С1Н2S-butyl),
27.27 (С1Н2S-butyl), 31.25 (С2Н2-butyl), 31.38 (С2Н2-
butyl), 32.08 (furan-СН2S), 61.00 (СН2О-ester), 62.97
d (СН2ОР, 2JРС 6.2 Hz), 112.08 d (С4-furan, 3JРС = 2.5
Hz), 114.34 d (С3-furan, 2JРС = 8.2 Hz), 133.52 d (=СН,
2JРС = 11.7 Hz), 136.74 d (=СР, 1JРС = 177.8 Hz), 141.45
(С5-furan), 150.00 d (С2-furan, 3JРС = 10.2 Hz), 164.26
2
δС, ppm: 16.37 d (СН3-phosphonate, JРС = 5.9 Hz),
28.21 (CH2SCN), 30.81 d (СН3-ketone, 4JРС = 1.3 Hz),
63.32 d (СН2ОР, 2JРС = 6.5 Hz), 112.22 (SCN), 117.63
d (С3-furan, 2JРС = 8.6 Hz), 119.84 d (С4-furan, 3JРС
=
3.8 Hz), 130.35 d (=СР, 1JРС = 180.3 Hz), 131.97 d (=СН,
2JРС = 2.7 Hz), 142.73 d (С2-furan,3JРС = 8.0 Hz), 142.87
3
d (С=О, JРС = 28.3 Hz). 31Р NMR spectrum (CDCl3),
3
(С5-furan), 199.08 d (С=О, JРС = 21.0 Hz). 31Р NMR
δР, ppm: 14.14.
spectrum (CDCl3), δР, ppm: 13.82.
4-(4-Chloromethylfur-3-yl)-4-(diethoxyphos-
phoryl)but-3-en-2-one (39) was prepared from furoyl
phosphonate 4. Yield 84%, brown syrup. 1H NMR spec-
trum (CDCl3), δ, ppm: 1.31 t (6Н, СН3-phosphonate,
4-(4-Butylthiomethylfur-3-yl)-4-(diethoxyphos-
phoryl)but-3-en-2-one (42) was prepared from furoyl
phosphonate 27. Yield 84%, yellowish brown syrup. 1H
NMR spectrum (CDCl3), δ, ppm: 0.90 t (3Н, С4Н3-butyl,
JНН = 7.2 Hz), 1.31 t (6Н, СН3, JНН = 7.2 Hz), 1.36 sextet
(2Н, С3Н2-butyl, JНН = 7.2 Hz), 1.54 quintet (2Н, С2Н2-
butyl, JНН = 7.2 Hz), 2.15 s (СН3-ketone), 2.44 t (2Н,
С1Н2S-butyl, JНН = 7.2 Hz), 3.49 s (2Н, furan-СН2S),
4.13 d. q (4Н, СН2ОР, JНН = 7.3 Hz, JРН = 14.0 Hz), 7.04
d (1Н, =СН, JРН = 23.2 Hz), 7.47 br. s (1Н, Н5-furan),
7.49 d (1Н, Н5-furan, JРН = 2.8 Hz). 13С NMR spectrum
(CDCl3), δС, ppm: 13.67 (С4Н3-butyl), 13.69 (С4Н3-
butyl), 16.33 d (СН3-phosphonate, 2JРС = 6.2 Hz), 21.96
(С3Н2-butyl), 24.96 (С1Н2S-butyl), 30.57 d (СН3-ketone,
4JРС = 1.3 Hz ), 31.23 (С2Н2-butyl), 31.43 (furan-СН2S),
JНН = 7.2 Hz), 2.16 s (3Н, СН3-ketone), 4.08–4.17 m (4Н,
СН2О-phosphonate), 4.49 s (2Н, CH2Cl), 7.08 d (1Н, ,
=СН, JРН = 23.2 Hz), 7.34 br. s (1Н, Н5-furan), 7.52 br.
s (1Н, Н5-furan). 13С NMR spectrum (CDCl3), δС, ppm:
16.30 d (СН3-phosphonate, 2JРС = 6.3 Hz), 30.70 d (СН3-
ketone, 4JРС = 1.3 Hz), 36.03 (CH2Cl), 63.11 d (СН2ОР,
2JРС = 6.3 Hz), 117.82 d (С3-furan,2JРС = 8.2 Hz), 122.74
d (С4-furan, 3JРС = 4.3 Hz), 130.91 d (=СР, 1JРС = 179.1
Hz), 131.95 d (=СН, 2JРС = 2.4 Hz), 142.26 d (С2-furan,
3JРС = 7.3 Hz), 142.55 (С5-furan), 199.00 d (С=О,
3JРС = 21.5 Hz). 31Р NMR spectrum (CDCl3), δР,
ppm.:14.22.
2
63.01 d (СН2ОР, JРС = 6.1 Hz), 118.33 d (С3-furan,
2JРС = 8.3 Hz), 122.27 d (С4-furan, 3JРС = 4.3 Hz), 131.58
d (=СР, 1JРС = 178.4 Hz), 131.96 d (=СН, 2JРС = 2.7 Hz),
Ethyl 3-(4-chloromethylfur-3-yl)-3-(diethoxy-
phosphoryl)acrylate (40) was prepared from furoyl
phosphonate 4. Yield 91%, brown syrup. 1H NMR spec-
3
141.66 (С5-furan), 141.98 d (С2-furan, JРС = 7.2 Hz),
3
199.15 d (С=О, JРС = 22.0 Hz). 31Р NMR spectrum
trum (CDCl3), δ, ppm: 1.17 t (3Н, СН3-ester, JНН
=
(CDCl3), δР, ppm: 14.67.
7.0 Hz), 1.29 t (6Н, СН3-phosphonate, JНН = 7.2 Hz),
4.06–4.13 m (6Н, СН2О-phosphonate, СН2О-ester),
4.40 s (2Н, CH2Cl), 6.89 d (1Н, =СН, JРН = 22.4 Hz),
7.32 s (1Н, Н5-furan), 7.50 s (1Н, Н5-furan). 13С NMR
spectrum (CDCl3), δС, ppm: 13.90 (СН3-ester), 16.30 d
(СН3-phosphonate, 2JРС = 6.2 Hz), 35.95 (CH2Cl), 61.10
Ethyl 3-(4-butylthiomethylfur-3-yl)-3-(diethoxy-
phosphoryl)acrylate (43) was prepared from furoyl
phosphonate 27. Yield 86%, yellowish brown syrup. 1H
NMR spectrum (CDCl3), δ, ppm: 0.89 t (1.5Н, С4Н3-
butyl, JНН = 7.2 Hz), 1.19 t (3Н, СН3-ester, JНН = 7.2 Hz),
1.36 sextet (2Н, С3Н2-butyl, JНН = 7.2 Hz), 1.53 quintet
(2Н, С2Н2-butyl, JНН = 7.2 Hz), 2.45 t (2Н, С1Н2S-butyl,
2
(СН2О-ester), 63.16 d (СН2ОР, JРС = 6.3 Hz), 122.94
d (С4-furan, 3JРС = 5.1 Hz), 124.01 d (С3-furan, 3JРС
=
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 8 2019

1618
PEVZNER, SOKOLOVA
JНН = 7.2 Hz), 3.44 s (2Н, furan-СН2S), 4.09–4.15 m (6Н,
СН2ОР, СН2О-ester), 6.88 d (1Н, , =СН, JРН = 22.4 Hz),
was kept in a vacuum (1 mmHg) for 1 h at room tem-
perature. Yield 0.20 g (38%), light brown syrup. 1H NMR
spectrum (CDCl3), δ, ppm: 1.35 t (6Н, СН3-phosphonate,
7.45 br. s (1Н, Н5-furan), 7.47 d (1Н, Н2-furan, JРН
=
2.8 Hz). 13СNMR spectrum (CDCl3), δС, ppm: 13.69
(С4Н3-butyl), 13.95 (СН3-ester), 16.34 d (СН3-
phosphonate, 2JРС = 6.1 Hz), 21.97 (С3Н2-butyl), 27.02
(С1Н2S-butyl), 31.30 (С2Н2-butyl), 31.67 (furan-СН2S),
J
НН = 7.0 Hz), 2.11 br. s (3Н, СН3-ketone), 4.09–4.20 m
(4Н, СН2О-phosphonate), 4.25 br. s (2Н, CH2N3), 6.61
d (1Н, Н4-furan, JНН = 1.2 Hz), 7.14 d (1Н, , =СН, JРН
=
22.4 Hz), 7.58 d (1Н, Н5-furan, JНН = 1.2 Hz). 13С NMR
spectrum (CDCl3), δС, ppm: 16.35 d (СН3-phosphonate,
2JРС = 6.5 Hz), 30.97 (СН3-ketone), 45.57 (CH2N3), 63.66
2
60.96 (СН2О-ester), 63.03 d (СН2ОР, JРС = 6.2 Hz),
118.23 d (С3-furan, 2JРС = 7.3 Hz), 122.65 d (С4-furan,
3JРС = 5.2 Hz), 133.61 d (=СН, 2JРС = 11.5 Hz), 135.87
2
d (СН2ОР, JРС = 5.4 Hz), 113.99 (С4-furan), 121.75 d
d (=СР, JРС = 178.3 Hz), 141.17 (С5-furan), 141.28
(С3-furan, 3JРС = 4.7 Hz), 128.13 d (=СР, JРС = 180.7
1
1
d (С2-furan, JРС = 6.0 Hz), 164.17 d (С=О, JРС
=
Hz), 131.81 d (=СН, 2JРС = 2.2 Hz), 144. 48 d (С5-furan,
4JРС = 2.8 Hz), 145.13 d (С2-furan, 2JРС = 7.2 Hz), 198.28
3
3
28.4 Hz). 31Р NMR spectrum (CDCl3), δР, ppm: 13.90.
3
d (С=О, JРС = 20.9 Hz). 31Р NMR spectrum (CDCl3),
4-(3-Thiocyanatomethylfur-2-yl)-4-(diethoxyphos-
phoryl)but-3-en-2-one (34). 0.34 g (3.5 mmol) of potas-
sium thiocyanate and 0.34 g (0.17 mmol) of potassium
iodide were added to a solution of 0.55 g (1.7 mmol) of
phosphonate 33 in 10 mLof acetonitrile. The mixture was
stirred for a day at room temperature, the precipitate was
filtered off, and the filtrate was evaporated. The residue
was dissolved in 20 mLof chloroform, washed with 5 mL
of water and with 5 mL of brine, and dried over sodium
sulfate. The solvent was removed, and the residue was
kept in vacuum (1 mmHg) for 1 h at room temperature.
δР, ppm: 12.87.
4-(4-Azidomethylfur-3-yl)-4-(diethoxyphospho-
ryl)but-3-en-2-one (46). 1.00 g (15.2 mmol) of so-
dium azide and 0.03 g (0.17 mmol) of potassium iodide
were added at room temperature to a solution of 2.45 g
(7.6 mmol) of phosphonate 39 in 50 mL of acetone. The
mixture was stirred for a week at room temperature,
and then the precipitate was filtered off. The filtrate
was evaporated, the residue was dissolved in 60 mL of
chloroform, washed with 20 mL of water and 20 mL of
brine, and dried over sodium sulfate.After removal of the
solvent, the residue was kept in vacuum (1 mmHg) for
1 h at room temperature. Yield 2.37 g (95%) light brown
syrup. 1H NMR spectrum (CDCl3), δ, ppm: 1.30 t (6Н,
СН3-phosphonate, JНН = 7.2 Hz), 2.15 br. s (3Н, СН3-
ketone), 4.09–4.14 m (4Н, СН2О-phosphonate), 4.18 br.
s (2Н, CH2N3), 7.14 d (1Н, , =СН, JРН = 23.6 Hz), 7.36
br. s (1Н, Н5-furan), 7.41 br. s (1Н, Н2-furan). 13С NMR
spectrum (CDCl3), δС, ppm: 16.31 d (СН3-phosphonate,
2JРС = 6.0 Hz), 30.91 (СН3-ketone), 44.82 (CH2N3), 63.10
1
Yield 0.32 g (54%), light brown syrup. H NMR spec-
trum (CDCl3), δ, ppm: 1.32 t (6Н, СН3-phosphonate,
JНН = 7.2 Hz), 2.07 s (3Н, СН3-ketone), 4.09–4.17 m
(4Н, СН2О-phosphonate), 4.14 s (2Н, CH2SCN), 6.66
d (1Н, Н4-furan, JНН = 2.0 Hz), 7.07 d (1Н, =СН, JРН
=
22.0 Hz), 7.50 d (1Н, Н5-furan, JНН = 2.0 Hz). 13С NMR
spectrum (CDCl3), δС, ppm: 16.31 d (СН3-phosphonate,
2JРС = 5.9 Hz), 29.51 (CH2SCN), 30.96 (СН3-ketone),
63.26 d (СН2ОР, 2JРС = 5.8 Hz), 112.68 (SCN), 113.07
d (С4-furan, 4JРС = 1.6 Hz), 121.07 d (С3-furan, 3JРС
=
4.6 Hz), 128.25 d (=СР, JРС = 181.0 Hz), 131.88 d
(=СН, 2JРС = 3.1 Hz), 144.32 d (С5-furan,4JРС = 2.3 Hz),
d (СН2ОР, JРС = 6.2 Hz), 117.75 d (С3-furan, JРС
=
1
2
2
7.9 Hz), 120.57 d (С4-furan, 3JРС = 4.7 Hz), 131.16 d
(=СР, 1JРС = 179.3 Hz), 131.93 d (=СН, 2JРС = 2.8 Hz),
144.54 d (С2-furan, 2JРС = 7.1 Hz), 198.92 d (С=О, 3JРС
=
3
19.9 Hz). 31Р NMR spectrum (CDCl3), δР, ppm: 12.45.
141.87 (С5-furan), 142.11 d (С2-furan, JРС = 6.9 Hz),
3
198.57 d (С=О, JРС = 21.6 Hz). 31Р NMR spectrum
4-(3-Azidomethylfur-2-yl)-4-(diethoxyphospho-
ryl)but-3-en-2-one (35). 0.21 g (3.5 mmol) of sodium
azide and 0.03 g (0.17 mmol) of potassium iodide were
added at room temperature to a solution of 0.52 g
(1.6 mmol) of phosphonate 33 in 10 mL of acetonitrile.
The mixture was stirred for 9 h at 70°C, and then the
precipitate was filtered off. The filtrate was evaporated,
the residue was dissolved in 20 mLof chloroform, washed
with 5 mL of water and 5 mL of brine, and dried over
sodium sulfate. After removal of the solvent, the residue
(CDCl3), δР, ppm: 14.20.
Reaction of chloromethyl derivatives 39, 40 with
morpholine (general procedure). 20 mmol of morpholine
was added with stirring to a solution of 10 mmol of chlo-
romethylfuran 39 or 40 in 30 mLof benzene. The mixture
was left at room temperature for 4 days and then extracted
with 5% hydrochloric acid (3×15 mL). The extract was
alkalified to pH = 9 by addition of sodium carbonate in
small portions with stirring. The mixture was saturated
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 8 2019

SYNTHESIS AND SELECTED REACTIONS OF 2(3)-FUROYL PHOSPHONATES
1619
2
with sodium chloride and extracted with chloroform
(3×20 mL). The extract was dried over sodium sulfate,
chloroform was removed, and the residue was kept in
vacuum (1 mmHg) for 1 h at room temperature.
66.95 (ОСН2-morpholine), 118.44 d (С3-furan, JРС
=
7.3 Hz), 121.51 d (С4-furan,3JРС 5.2 Hz), 132.09 d (=СН,
2JРС = 11.5 Hz), 136.12 d (=СР, 1JРС = 178.9 Hz), 141.01
d (С2-furan, JРС = 6.1 Hz), 141.35 (С5-furan), 164.17
d (С=О, JРС = 28.5 Hz). 31Р NMR spectrum (CDCl3),
3
3
4-[4-(N-Morpholinomethyl)fur-3-yl]-4-(dieth-
oxyphosphoryl)but-3-en-2-one (44) was prepared from
compound 39. Yield 85%, light brown syrup. 1H NMR
spectrum (CDCl3), δ, ppm: 1.30 t (6Н, СН3-phosphonate,
JНН = 7.2 Hz), 2.16 br. s (3Н, СН3-ketone), 2.86 d (4Н,
NСН2-morpholine, JНН = 4.8 Hz), 3.19 s (2Н, NСН2-
furan), 3.62 d (4Н, ОСН2-morpholine, JНН = 4.8 Hz),
4.05–4.15 m (4Н, СН2О-phosphonate), 6.98 d (1Н, ,
=СН, JРН = 23.6 Hz), 7.38 br. s (1Н, Н5-furan), 7.39
δР, ppm: 14.20.
FUNDING
This study was carried out in the scope of basic part
of state project of Ministry of Education and Science of
the Russian Federation (project no 4.5554.2017/8.9) using
the equipment of the Engineering Center of St. Petersburg
State Institute of Technology (Technical University) and
the Resource Center of St. Petersburg State University
“Methods of Analysis of Composition of Substance.”
d (1Н, Н2-furan, JНН = 1.6 Hz). 13С NMR spectrum
2
(CDCl3), δС, ppm: 16.34 d (СН3-phosphonate, JРС
=
6.1 Hz), 30.66 (СН3-ketone), 46.40 (NСН2-furan), 53.66
2
(NСН2-morpholine), 62.90 d (СН2ОР, JРС = 6.4 Hz),
CONFLICT OF INTEREST
No conflict of interest was declared by the authors.
REFERENCES
2
66.84 (ОСН2-morpholine), 118.65 d (С3-furan, JРС
=
7.8 Hz), 121.69 d (С4-furan, 3JРС = 4.8 Hz), 132.03 d
(=СН, 2JРС = 2.6 Hz), 132.06 d (=СР, 1JРС = 178.6 Hz),
141.05 d (С2-furan, JРС = 8.5 Hz), 141.99 (С5-furan),
3
198.77 d (С=О, JРС = 22.4 Hz). 31Р NMR spectrum
3
1. Pevzner, L.M., Ponyaev, A.I., Russ. J. Gen. Chem., 2019,
vol. 89, no. 1, p. 49. doi 10.1134/S1070363219010080
(CDCl3), δР, ppm: 14.89.
2. Pevzner, L.M., Russ. J. Gen. Chem., 2019, vol. 89,
Ethyl 3-[4-(N-morpholinomethyl)fur-3-yl]-3-
(diethoxyphosphoryl)acrylate (45) was prepared from
compound 40. Yield 55%, light brown syrup. 1H NMR
spectrum (CDCl3), δ, ppm: 1.18 t (3Н, СН3-ester), 1.29 t
(6Н, СН3-phosphonate, JНН = 7.2 Hz), 2.85 d (4Н, NСН2-
morpholine, JНН = 4.6 Hz), 3.22 s (2Н, NСН2-furan),
3.63 d (4Н, ОСН2-morpholine, JНН = 4.6 Hz), 4.04–4.15
m (6Н, СН2О-phosphonate, СН2О-ester), 6.80 d (1Н,
=СН, JНН = 22.8 Hz), 7.35 br. s (1Н, Н5-furan), 7.38 br.
no. 2, p. 244. doi 10.1134/S1070363219020129
3. US Patent 5840917A, 1998
4. Levy, G.C. and Lichter, R.L., Nitrogen-15 Nuclear
Magnetic Resonance Spectroscopy, New York: Wiley
Interscience, 1979, p. 102.
5. Mel’nykov, V.V., Baeva, L.F., and Gidaspov, B.V., Zh.
Prikl. Spectroskop., 1973, vol. 18, no. 1, p. 87.
6. Pevzner, L.M., Russ. J. Gen. Chem., 2011, vol. 81, no. 1,
s (1Н, Н2-furan). 13С NMR spectrum (CDCl3), δС, ppm:
p. 56. doi 10.1134/S1070363211010099
2
13.98 (СН3-ester), 16.35 d (СН3-phosphonate, JРС
=
7. Pudovik, A.I., Batyeva, E.S., Nizamov, I.S., Zametdino-
va, G.U., and Al’fonsov, V.A., Bull. Acad. Sci. USSR. Div.
Chem. Sci., 1988, vol. 37, no. 2, p. 389.
6.2 Hz), 46.43 (NСН2-furan), 53.60 (NСН2-morpholine),
2
60.87 (СН2О-ester), 62.90 d (СН2ОР, JРС = 6.1 Hz),
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 8 2019