Substituted Butanolides and Butenolides: XVII. Substituted 3-(Furan-2-ylmethylidene)furan-2(3H)-ones and 3-(Furan-2-ylmethylidene)dihydrofuran-2(3H)-ones

Article abstract of DOI:10.1134/S1070428018070102

A number of furan-2-ylmethylidene-substituted lactones were synthesized by condensation of 5-alkylfuran-2(3H)-ones and 4-alkyldihydrofuran-2(3H)-ones with 5-substituted furan-2-carbaldehydes. The reactivity of furan-2(3H)-ones was higher than that of furan-2(5H)-ones due to formation of intermediate conjugated anion. The condensation of 4-alkyldihydrofuran-2(3H)-ones with furan-2-carbaldehydes required more severe conditions than the condensation with furan-2(3H)-ones. The substituent in the furan ring affects the reaction time and yield.

Full text of DOI:10.1134/S1070428018070102

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2018, Vol. 54, No. 7, pp. 1031–1034. © Pleiades Publishing, Ltd., 2018.
Original Russian Text © L.A. Badovskaya, L.N. Sorotskaya, N.D. Kozhina, T.Ya. Kaklyugin, 2018, published in Zhurnal Organicheskoi Khimii, 2018,
Vol. 54, No. 7, pp. 1027–1030.
Substituted Butanolides and Butenolides:
XVII.* Substituted 3-(Furan-2-ylmethylidene)furan-2(3H)-ones
and 3-(Furan-2-ylmethylidene)dihydrofuran-2(3H)-ones
a
a
a
a
L. A. Badovskaya , L. N. Sorotskaya ,* N. D. Kozhina , and T. Ya. Kaklyugina
a
Kuban State Technological University, ul. Moskovskaya 2, Krasnodar, 350072 Russia
*
e-mail: Sorotskaja@rambler.ru
Received December 29, 2017
Abstract—A number of furan-2-ylmethylidene-substituted lactones were synthesized by condensation of
-alkylfuran-2(3H)-ones and 4-alkyldihydrofuran-2(3H)-ones with 5-substituted furan-2-carbaldehydes. The
5
reactivity of furan-2(3H)-ones was higher than that of furan-2(5H)-ones due to formation of intermediate
conjugated anion. The condensation of 4-alkyldihydrofuran-2(3H)-ones with furan-2-carbaldehydes required
more severe conditions than the condensation with furan-2(3H)-ones. The substituent in the furan ring affects
the reaction time and yield.
DOI: 10.1134/S1070428018070102
While developing concepts of the condensation of
furan-2-ones and dihydrofuran-2-ones with carbonyl
compounds, we studied reactions of 5-alkylfuran-
presence of sodium acetate or triethanolamine as
catalyst [4]. Among furancarbaldehydes, furfural and
its 5-iodo and 5-nitro derivatives were used.
2
5
(3H)-ones and 4-alkyldihydrofuran-2(3H)-ones with
-substituted furan-2-carbaldehydes with the goal of
In order to exclude the use of toxic benzene, sim-
plify the reaction conditions, and obtain new 5-alkyl-
finding out peculiar features of the condensation of
lactones differing from furan-2(5H)-one by the posi-
tion or presence of C=C double bond in the lactone
ring. We obtained new ylidene-substituted lactones that
are promising as potential biologically active com-
pounds and intermediate products for organic synthe-
sis. We previously reported the synthesis of 5-[aryl-
3
-(furan-2-ylmethylidene)furan-2(3H)-ones, 5-alkyl-
furan-2(3H)-ones 1 and 2 were brought into conden-
sation with substituted furan-2-carbaldehydes 3a–3h in
ethanol at room temperature in the presence of piperi-
dine as catalyst (Scheme 1). In all cases, the initial
lactone was taken in excess, the ratio furan-2(3H)-one‒
aldehyde‒catalyst being 1:0.5:0.25.
The reaction time and yield did not depend on the
nature of alkyl substituent in the lactone ring but
depended on the substituent in the furan ring of 3. The
reactions of 1 and 2 with 5-arylfurancarbaldehydes
required a longer time than with furfural and its 5-alkyl
(
hetaryl)methylidene]furan-2(5H)-ones on the basis of
unsub-stituted furan-2(5H)-one [2, 3].
The reactions of a number of aromatic aldehydes
and furancarbaldehydes with alkyl- and arylfuran-2-
ones were carried out in benzene on heating in the
Scheme 1.
O
X
+
R
O
X
CHO
–H O
R
O
O
O
2
O
1
, 2
3a–3h
4a–4d, 5a–5d
1
, R = Me; 2, R = Bu; 3, X = H (a), Me (b), Cl (c), Br (d), Ph (e), 4-MeC
6
H
4
(f), 4-BrC
6
H
4
(g), 4-O
2
NC
6
H
5
(h);
(d).
4
, R = Me, X = H (a), Me (b), Cl (c), Br (d); 5, R = Bu, X = Ph (a), 4-MeC
6
H
4
(b), 4-BrC
6
H
4
(c), 4-O
2
NC
6
H
4
*
For communication XVI, see [1].
1
031

1
032
BADOVSKAYA et al.
and 5-halo derivatives. Electron-donating substituents
in both furan and benzene rings accelerated the reac-
tion and increased the yield of the condensation prod-
ucts. Electron-withdrawing nitro group in aldehyde 3h
appreciably inhibited the reaction, and the yield of 5d
was lower than the yields of 5a and 5b. Analogous
substituent effects were observed in the reactions of
furan- and 5-arylfuran-2-carbaldehydes with furan-
Scheme 3.
R
+
O
X
CHO
O
O
6
, 7
3b, 3d
R
O
O
X
2
(5H)-ones [2]. However, in the latter case the yields
of ylidene derivatives having no aryl substituent in the
-position were considerably lower than in the reac-
–
H O
2
O
8
a–8b, 9
5
tions with furan-2(3H)-ones. The higher reactivity of
furan-2(3H)-ones can be rationalized by higher acidity
of the 2-H proton therein due to direct electron-with-
drawing effect of the neighboring C=C double bond
and oxo group which is a stronger electron acceptor
than the carbonyl oxygen atom in furan-2(5H)-one.
As a result, conjugation-stabilized anion A is generated
from furan-2(3H)-ones more readily than from furan-
6, R = cyclo-C
6
H
11; 7, R = PhCH
2
6 11
; 8, R = cyclo-C H ,
2
X = Me (a), Br (b); 9, R = PhCH , X = Me.
3
d with alkyldihydrofuran-2(3H)-ones 6 and 7 re-
quired more severe conditions and longer reaction
time. The reaction occurred on heating to 70°C in the
presence of a strong base (sodium ethoxide).
All the synthesized compounds are yellow or
orange crystalline solids, readily soluble in chloroform,
benzene, toluene, acetone, and boiling ethanol, poorly
soluble in diethyl ether, and insoluble in water. Their
electronic absorption spectra displayed the main maxi-
mum at λ 330‒450 nm and lower maxima at λ 240‒
290 nm. The UV absorption maxima of butanolides 8
and 9 with a saturated lactone ring were observed
at shorter wavelengths (Δλmax ≤50 nm) than those of
analogous ylidenefuran-2(3H)-ones 4 and 5. The
reason is that the double bond in the lactone ring of 4
and 5 is included in the common conjugation system.
This is consistent with the fact that in the UV spectra
of aryl-3-(furan-2-ylmethylidene)furan-2(5H)-ones [2],
in which the conjugation system is more even than
in isomeric (furan-2-ylmethylidene)furan-2(3H)-ones,
longwave shift of the absorption maximum was
observed.
2
(5H)-one (Scheme 2). Intermediate formation of
conjugated anion is followed from the unusual path
of the reaction of furan-2(5H)-one with cyclic tertiary
enamines [5].
Scheme 2.
H
H
H
HB+
–
H+ + B:
+
B:
O
O
O
O
O
O
A
The anion acts as nucleophile toward the carbonyl
group of furancarbaldehydes. The adduct thus formed
loses water molecule to produce 3-(furan-2-ylmethyli-
dene)furan-2(3H)-ones 4a–4d and 5a–5d, which is
energetically favorable due to formation of a conjuga-
tion system comprising the entire molecule.
The IR spectra of compounds 4, 5, 8, and 9 showed
an absorption band at 1740‒1780 cm , which is typi-
Taking the aforesaid into account, it became
possible to explain why neither furan-2(5H)-ones nor
furan-2(3H)-ones reacted with aliphatic and alicyclic
aldehydes under the conditions of facile condensation
with furancarbaldehydes.
–1
cal of C=O stretching vibrations of lactones. This band
was not split as in the spectra of ylidenefuran-2(5H)-
ones, in which the carbonyl group is conjugated with
the C=C double bond. The νC=O frequency of saturated
lactones 8 and 9 is lower than that of compounds 4 and
having an endocyclic double bond conjugated with
the carbonyl group. In addition, absorption bands at
630–1665 (νC=C), 1215–1230, 1100–1125, and
160–1190 cm (ν C‒O‒C, ν C‒O, lactone) were
An indirect support of the proposed mechanism is
provided by comparison of the above discussed reac-
tions of furan-2(5H)-ones and furan-2(3H)-ones with
the condensation of 4-substituted tetrahydrofuran-2-
ones with furancarbaldehydes (Scheme 3).
5
1
1
–
1
Anion A could not be generated in the reaction with
dihydrofuran-2(3H)-ones, and the conjugation system
of 3-(furan-2-ylmethylidene)dihydrofuran-2(3H)-ones
present in the IR spectra of 4, 5, 8, and 9, as well as
bands belonging to vibrations of C‒O‒C groups and
C–H bonds of the furan and benzene rings (3100‒
3140, 1010‒1025, 1030‒1080, 750‒760 cm ). The
structure of compounds 4, 5, 8, and 9 was also con-
–
1
8
a, 8b, and 9 does not include the lactone ring. There-
fore, the condensation of furancarbaldehydes 3b and
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 7 2018

SUBSTITUTED BUTANOLIDES AND BUTENOLIDES: XVII.
1033
1
firmed by H NMR spectra; as examples, the spectra of
5
0.01 mol of 5-alkylfuran-2(3H)-one 1 or 2 in 25 mL of
ethanol, and 0.005 mol of furancarbaldehyde 3 was
then added with stirring. The mixture was stirred for
a and 8a are considered below.
H2
H2
O
1
h at room temperature and was then kept in a re-
H1
H1
H3
H3
H4
frigerator for crystallization. The precipitate was fil-
tered off, the mother liquor was evaporated by half,
and the residue was kept in a refrigerator to obtain
an additional amount of the product. The product was
recrystallized from ethanol.
H4
Cy
H5
H6
O
Ph
Me
Bu
O
O
O
O
5
a
8a
b. A solution of 0.01 mol of dihydrofuran-2(3H)-
one 6 or 7 and 0.005 mol of furancarbaldehyde 3 in
Protons on the double-bonded carbon atom in
unsaturated lactones resonate in a fairly narrow range,
δ 6.6–7.4 ppm. The 1-H signal (as most deshielded) is
located in a weaker field, signals from protons in the
furan and benzene rings appear in their usual positions.
The butyl substituent in the lactone ring of 5a gave
signals in the region δ 0.90‒3.65 ppm (a complex
multiplet). The 1-H proton of 8 and 9 resonated almost
in the same region as the corresponding proton of 4
and 5. The 4-H proton is coupled with 5-H and 6-H,
and its signal is shifted significantly upfield relative to
the 4-H signal of unsaturated lactones. The 5-H and
1
0 mL of ethanol was cooled in an ice bath, and 2 mL
(
0.007 mol) of a 25% solution of sodium ethoxide in
ethanol was added dropwise. Ethanol, 20 mL, was then
added, and the mixture was stirred for 1.5 h at room
temperature and for 2 h at 50‒60°C until the initial
aldehyde disappeared. The mixture was treated with
1
0% sulfuric acid to neutral reaction, stirred for 1 h,
and evaporated by 50‒70%. The residue was kept in
a refrigerator, and the precipitate was filtered off and
recrystallized from ethanol.
3
-[(Furan-2-yl)methylidene]-5-methylfuran-
6
-H signals of 8 and 9 constitute the AB part of ABX
2
(3H)-one (4a). Yield 75%, yellow crystals, mp 76‒
spin system (where X is 4-H) typical of 3-substituted
butanolides. Protons of the methyl group in the furan
ring appear at δ 2.35 ppm.
7
7°C (from EtOH). UV spectrum (EtOH): λ 368 nm
max
–1
(logε 4.28). IR spectrum, ν, cm : 3100 (C‒H), 1765
C=O), 1630 (C=C), 1225, 1160, 1125 (C‒O‒C), 1030,
(
The condensation products of substituted buten-
olides and butanolides with furancarbaldehydes con-
tain highly reactive lactone and furan rings and are
promising as intermediate products for synthetic
organic chemistry and potentially biologically active
compounds.
1020, 750. Found, %: C 68.53; H 4.63. C10
culated, %: C 68.18; H 4.55.
5-Methyl-3-[(5-methylfuran-2-yl)methylidene]-
furan-2(3H)-one (4b). Yield 85%, yellow crystals,
mp 108‒109°C (from EtOH). UV spectrum (EtOH):
H O . Cal-
8 3
–1
λmax 383 nm (logε 4.30). IR spectrum, ν, cm : 3110
(
(
C‒H), 1760 (C=O), 1640 (C=C), 1220, 1160, 1120
C‒O‒C), 1040, 1020, 760. Found, %: C 69.51;
EXPERIMENTAL
H 5.32. C H O . Calculated, %: C 69.47; H 5.26.
11
10
3
The UV spectra were measured on a Specord UV-
Vis spectrophotometer from solutions in ethanol with
3
-[(5-Chlorofuran-2-yl)methylidene]-5-methyl-
furan-2(3H)-one (4c). Yield 60%, yellow crystals,
mp 107‒108°C (from EtOH). UV spectrum (EtOH):
–
5
a concentration of 10 M. The IR spectra were record-
ed on a Specord UR-20 spectrometer from samples
–1
λmax 376 nm (logε 4.30). IR spectrum, ν cm : 3110
1
dispersed in mineral oil. The H NMR spectra were
(
(
C‒H), 1780 (C=O), 1650 (C=C), 1220, 1160, 1120
C‒O‒C), 1065, 1010, 755. Found, %: C 56.94;
taken on Bruker WM-250 and AC-300 spectrometers
at 250 and 300 MHz, respectively, using CDCl as
3
H 3.37; Cl 16.89. C H ClO . Calculated, %: C 57.01;
10
7
3
solvent and tetramethylsilane as internal standard.
H 3.32; Cl 16.86.
5
-Butylfuran-2(3H)-one [6], 4-cyclohexyl- and
3
-[(5-Bromofuran-2-yl)methylidene]-5-methyl-
4
2
-benzyldihydrofuran-2(3H)-ones [7], and 5-arylfuran-
-carbaldehydes [8] were synthesized according to
furan-2(3H)-one (4d). Yield 62%, yellow crystals,
mp 111‒112°C (from EtOH). UV spectrum (EtOH):
–1
known procedures.
λmax 380 nm (logε 4.32). IR spectrum, ν, cm : 3120
(C‒H), 1780 (C=O), 1650 (C=C), 1210, 1160, 1120
(C‒O‒C), 1070, 1010, 760. Found, %: C 47.00;
H 2.78; Br 31.43. C H BrO . Calculated, %: C 47.06;
Condensation of 5-alkylfuran-2(3H)-ones 1 and
2
7
and 4-substituted dihydrofuran-2(3H)-ones 6 and
with furancarbaldehydes (general procedure).
1
0
7
3
a. Piperidine, 0.0025 mol, was added to a solution of
H 2.74; Br 31.37.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 7 2018

1
034
BADOVSKAYA et al.
5
-Butyl-3-[(5-phenylfuran-2-yl)methylidene]-
(1H, 4-H), 3.96 m (1H, 6-H), 4.08 m (1H, 5-H), 6.00 d
(1H, 3-H), 6.40 d (1H, 2-H), 6.87 d (1H, 1-H).
Found, %: C 73.88; H 7.63. C H O . Calculated, %:
furan-2(3H)-one (5a). Yield 70%, yellow crystals,
mp 91‒92°C (from EtOH). UV spectrum (EtOH):
λmax 330 nm (logε 4.00). IR spectrum, ν, cm : 3100
1
6
20
3
–1
C 73.85; H 7.69.
(
(
C‒H), 1760 (C=O), 1645 (C=C), 1220, 1160, 1120
C‒O‒C), 1055, 1025, 750. H NMR spectrum, δ,
3
-[(5-Bromofuran-2-yl)methylidene]-4-cyclo-
1
hexyldihydrofuran-2(3H)-one (8b). Yield 50%,
yellow crystals, mp 137‒138°C (from EtOH). UV
spectrum (EtOH): λ
trum, ν, cm : 3125 (C‒H), 1750 (C=O), 1665 (C=C),
215, 1170, 1100 (C‒O‒C), 1060, 1025, 1050
(C‒O‒C). H NMR spectrum, δ, ppm: 1.10‒2.40 m
ppm: 1.20–3.25 m (9H, Bu), 6.61 s (1H, 4-H), 6.98 s
1H, 1-H), 6.99 d (1H, 3-H), 7.05 d (1H, 2-H), 7.32–
.85 m (5H, Harom). Found, %: C 77.15; H 6.18.
C H O . Calculated, %: C 77.55; H 6.12.
(
7
332 nm (logε 4.36). IR spec-
max
–1
1
9
18
3
1
1
5
-Butyl-3-{[5-(4-methylphenyl)furan-2-yl]-
methylidene}furan-2(3H)-one (5b). Yield 80%,
yellow crystals, mp 104‒105°C (from EtOH). UV
(10H, CH in C H ), 2.50 s (1H, CH in C H ), 3.70 s
2
6
11
6
11
(1H, 4-H), 4.21 m (1H, 6-H), 4.60 m (1H, 5-H), 6.50 d
(1H, 3-H), 6.70 d (1H, 2-H), 7.33 d (1H, 1-H). Found,
%: C 55.32; H 5.25; Br 24.67. C H BrO . Calculated,
spectrum (EtOH): λ
trum, ν, cm : 3120, 3100 (C‒H), 1760 (C=O), 1650
380 nm (logε 4.40). IR spec-
max
–
1
15
17
3
(
C=C), 1230, 1165, 1120 (C‒O‒C), 1080, 1030, 760.
%: C 55.38; H 4.23; Br 24.61.
1
H NMR spectrum, δ, ppm: 1.00–3.55 m (9H, Bu),
4
-Benzyl-3-[(5-methylfuran-2-yl)methylidene]-
2
7
7
.5 m (3H, CH ), 6.61 s (1H, 4-H), 6.96 s (1H, 1-H),
.05 d (1H, 3-H), 7.09 d (1H, 2-H), 7.28 d (2H, Harom),
.69 d (2H, Harom). Found, %: C 77.25; H 6.55.
3
dihydrofuran-2(3H)-one (9). Yield 80%, yellow
crystals, mp 116‒118°C (from EtOH). UV spectrum
–1
(
EtOH): λmax 330 nm (logε 4.40). IR spectrum, ν, cm :
C H O . Calculated, %: C 77.32; H 6.39.
2
0
20
3
3
140 (C‒H), 1740 (C=O), 1665 (C=C), 1215, 1190,
1
3
-{[5-(4-Bromophenyl)furan-2-yl]methylidene}-
-butylfuran-2(3H)-one (5c). Yield 73%, yellow
crystals, mp 210‒211°C (from EtOH). UV spectrum
1155 (C‒O‒C), 1055, 1025, 1010. H NMR spectrum,
5
δ, ppm: 2.40 s (3H, CH ), 2.80 s (1H, 4-H), 3.11 m
3
(
2H, CH Ph), 4.10 m (1H, 6-H), 4.20 m (1H, 5-H),
2
–1
(
EtOH): λmax 385 nm (logε 4.45). IR spectrum, ν, cm :
6.25 d (1H, 3-H), 6.83 d (1H, 2-H), 7.18 d (1H, 1-H),
.13 m (5H, Ph). Found, %: C 76.21; H 5.95.
C H O . Calculated, %: C 76.12; H 5.97.
3
100 (C‒H), 1770 (C=O), 1650 (C=C), 1220, 1165,
7
1
1110 (C‒O‒C), 1035, 1010, 760. H NMR spectrum, δ,
1
7
16
3
ppm: 0.90–3.60 m (9H, Bu), 6.61 s (1H, 4-H), 6.69 s
(
(
1H, 1-H), 7.09 d (1H, 3-H), 7.16 d (1H, 2-H), 7.62 d
2H, Harom), 7.77 d (2H, Harom). Found, %: C 61.18;
REFERENCES
H 4.52; Br 21.52. C H BrO . Calculated, %: C 68.13;
H 4.56; Br 21.45.
1. Tyukhteneva, Z.I. and Badovskaya, L.A., Russ. J. Org.
Chem., 2002, vol. 38, p. 1042.
19
17
3
2
. Sorotskaya, L.N., Badovskaya, L.A., Kaklyugina, T.Ya.,
Belen’kii, L.I., Ignatenko, A.V., Krutoshikova, A., and
Panieva, L.A., Zh. Org. Khim., 1989, vol. 25, p..
. Kaklugina, T.Ya., Badovskaya, L.A., Sorotskaya, L.N.,
and Kozhina, N.D., Collect. Czech. Chem. Commun.,
1986, vol. 51, p. 2181.
5
-Butyl-3-{[5-(4-nitrophenyl)furan-2-yl]methyli-
dene}furan-2(3H)-one (5d). Yield 65%, orange
crystals, mp 220‒222°C (from EtOH). UV spectrum
EtOH): λmax 450 nm (logε 4.10). IR spectrum, ν, cm :
130 (C‒H), 1775 (C=O), 1655 (C=C), 1220, 1160,
110 (C‒O‒C), 1035, 1020, 760. H NMR spectrum, δ,
ppm: 1.20–3.65 m (9H, Bu), 6.63 s (1H, 4-H), 7.35 s
1H, 1-H), 7.00 d (1H, 3-H), 7.11 d (1H, 2-H), 8.02 d
2H, Harom), 8.29 d (2H, Harom). Found, %: C 67.20;
H 5.09; N 4.17. C H NO . Calculated, %: C 67.26;
H 5.01; N 4.13.
–1
3
(
3
1
1
4
5
. Marrian, D.H., Russel, P.B., and Todd, A.R., Biochem. J.,
1
949, vol. 45, p. 533.
(
(
. Naidenov, Yu.V., Badovskaya, L.A., Belen’kii, L.I.,
Struchkov, Yu.T., Lozovskii, A.A., Chernega, A.N., and
Antipin, M.Yu., Zh. Org. Khim., 1991, vol. 27, p. 1715.
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Ostroumov, I.G., Chem. Heterocycl. Compd., 1987,
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. Muzychenko, G.F., Glukhovtsev, V.G., Ignatenko, A.I.,
Kozhina, N.D., Nikishin, G.I., Badovskaya, L.A.,
and Kul’nevich, V.G., USSR Inventor’s Certificate
no. 806683, 1981; Byull. Izobret., 1981, no. 7.
1
9
17
3
6
7
4
-Cyclohexyl-3-[(5-methylfuran-2-yl)methyli-
dene]dihydrofuran-2(3H)-one (8a). Yield 82%,
yellow crystals, mp 150‒151°C (from EtOH). UV
spectrum (EtOH): λ
trum, ν, cm : 3125 (C‒H), 1750 (C=O), 1650 (C=C),
220, 1180, 1120 (C‒O‒C), 1050, 1010. H NMR
330 nm (logε 4.37). IR spec-
max
–
1
1
1
spectrum, δ, ppm: 1.20‒1.90 m (10H, CH in C H ),
8. Jurášek, A., Kada, R., Nartvoň, A., and Uher, M., Základy
organickej syntézy, Praha, 1975, p. 389.
2
6
11
2
.32 s (3H, CH ), 2.52 s (1H, CH in C H ), 3.49 s
3 6 11
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 7 2018