Synthesis of functionally substituted furan and resorcinol derivatives from dimethyl 3-oxopentanedioate

Article abstract of DOI:10.1134/S1070428017060239

The alkylation of dimethyl 3-oxopentanedioate with 1,2-dibromoethane and 1,2,3-tribromopropane afforded C,C-(cyclopropane derivative) and C,O-dialkylation products. The initial trioxo compound underwent partial self-condensation to produce resorcinol deri

Full text of DOI:10.1134/S1070428017060239

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2017, Vol. 53, No. 6, pp. 950–952. © Pleiades Publishing, Ltd., 2016.
Original Russian Text © V.M. Ismailov, G.G. Ibragimova, N.D. Sadykhova, Z.A. Mamedova, N.N. Yusubov, 2017, published in Zhurnal Organicheskoi
Khimii, 2017, Vol. 53, No. 6, pp. 933–935.
SHORT
COMMUNICATIONS
Synthesis of Functionally Substituted Furan and Resorcinol
Derivatives from Dimethyl 3-Oxopentanedioate
V. M. Ismailov, G. G. Ibragimova, N. D. Sadykhova, Z. A. Mamedova, and N. N. Yusubov*
Baku State University, ul. Z. Khalilova 23, Baku, AZ-1148 Azerbaijan
*e-mail: yniftali@gmail.com
Received January 18, 2017
Abstract—The alkylation of dimethyl 3-oxopentanedioate with 1,2-dibromoethane and 1,2,3-tribromo-
propane afforded C,C- (cyclopropane derivative) and C,O-dialkylation products. The initial trioxo compound
underwent partial self-condensation to produce resorcinol derivative.
DOI: 10.1134/S1070428017060239
A convenient procedure for the synthesis of func-
tionally substituted furans is based on the alkylation of
β-dicarbonyl compounds with 1,2,3-trihaloalkanes [1].
Reactions of polycarbonyl compounds with di- and
trihaloalkanes allow alternative pathways which may
be varied by changing the conditions and reactant
nature.
C,C-dialkylation product) and methyl 2-(2-methoxy-2-
oxoethyl)-4,5-dihydrofuran-3-carboxylate (3, C,O-di-
alkylation product) (Scheme 1). Presumably, the
primary C-alkylation product (A) undergoes further
intramolecular C- or O-alkylation, yielding diester 2
or 3. The product structure was confirmed by 1H NMR
1
spectra. The H NMR spectrum of 2 displayed four
singlets due to protons of the methoxy and methylene
groups, while the spectrum of 3 showed three singlets
and two multiplets. Analogous reaction was described
in [2, 3]; it was carried out in the presence and in the
absence of acetals and ortho esters, and only C,C-di-
alkylation product was isolated.
Herein, we describe a one-step synthesis of func-
tionally substituted furan and resorcinol derivatives by
alkylation of dimethyl 3-oxopentanedioate (1) with di-
and trihaloalkanes.
Tricarbonyl compound 1 reacted with 1,2-dibromo-
ethane in DMSO in the presence of potassium carbo-
nate at 50–60°C to give a mixture of methyl 1-(3-me-
thoxy-3-oxopropanoyl)cyclopropane-1-carboxyate (2,
The reaction of 1 with 1,2,3-tribromopropane af-
forded dimethyl 2-(2-bromoprop-2-en-1-yl)-3-oxopen-
Scheme 1.
O
O
O
O
O
O
O
O
OMe
K2CO3, DMSO
Br
+
Br
MeO
OMe
MeO
OMe
MeO
OH
Br
Br
1
A
–Br–
–Br–
COOMe
COOMe
O
O
O
MeO
OMe
O
2
3
950

SYNTHESIS OF FUNCTIONALLY SUBSTITUTED FURAN
951
Scheme 2.
O
O
O
Me
COOMe
COOMe
K2CO3, DMSO
Br
1
+
+
MeO
OMe
Br
Br
O
CH2
Br
4
5
Scheme 3.
COOMe
Me
COOMe
COOMe
OH
K2CO3, DMSO, ∆
1
+
HO
OH
HO
COOMe
COOMe
6
7
tanedioate (4) and methyl 4-methyl-2-(2-methoxy-2-
oxoethyl)furan-3-carboxylate (5) (Scheme 2). Furan 5
is likely to be formed according to the mechanism
proposed previously [1], which implies rearrangement
of primary alkylation product 4, intramolecular O-al-
kylation, and prototropic isomerization. Compound 4
was converted completely to substituted furan 5 in the
a mixture of 0.05 mol of diester 1 and 0.05 mol of
calcined potassium carbonate in 100 mL of DMSO.
The mixture was stirred for 3 h at 20°C and for 5 h at
70°C, cooled, and treated with water and diethyl ether
(3×100 mL). The combined extracts were dried over
anhydrous MgSO4, the solvent was distilled off, and
the residue was distilled under reduced pressure.
presence of K2CO3 in DMSO at 60°C (4 h), which
confirmed the proposed mechanism.
Methyl 1-(3-methoxy-3-oxopropanoyl)cyclopro-
pane-1-carboxylate (2). Yield 2.6 g (15%), bp 95°C
1
In these experiments, acidification of the aqueous
phase with aqueous HCl led to separation of amor-
phous crystals which were identified as a mixture of
two resorcinol derivatives. By recrystallization we
isolated dimethyl 2,4-dihydroxy-6-(2-methoxy-2-oxo-
ethyl)- and 2,4-dihydroxy-6-methylbenzene-1,3-dicar-
boxylates 6 and 7 (Scheme 3). Presumably, diester 6 is
formed via intermolecular Claisen condensation of
compound 1 with subsequent intramolecular alkyla-
tion, dehydration, and prototropic isomerization.
Partial hydrolysis and decarboxylation of 6 during the
reaction yields compound 7.
(3 mm). H NMR spectrum, δ, ppm: 1.48 s (4H,
CH2CH2), 3.60 s (3H, CH3O), 3.65 s (3H, CH3O),
3.68 s (2H, CH2CO). Found, %: C 56.34; H 5.42.
C9H12O5. Calculated, %: C 56.19; H 5.71.
Methyl 2-(2-methoxy-2-oxoethyl)-4,5-dihydro-
furan-3-carboxylate (3). Yield 2.2 g (12%), bp 115°C
1
(3 mm). H NMR spectrum, δ, ppm: 2.7 m (2H,
CH2C=), 3.50 s (3H, CH3O), 3.65 s (3H, CH3O), 3.68 s
(2H, CH2CO), 4.40 m (2H, CH2CO). Found, %:
C 55.81; H 5.43. C9H12O5. Calculated, %: C 56.19;
H 5.71.
Dimethyl 2-(2-bromoprop-2-en-1-yl)-3-oxopen-
tanedioate (4). Yield 2.7 g (14%), bp 85°C (3 mm).
Found, %: C 40.44; H 4.63; Br 27.56. C10H13BrO5.
Calculated, %: C 40.95; H 4.43; Br 27.30.
The low yields of the alkylation products of 1 with
mono- and polyhaloalkanes suggest a concurrent proc-
ess involving only compound 1 and no alkylating
agent. By special experiment we showed that com-
pound 1 in the absence of alkylating agent undergoes
self-condensation to give substituted resorcinol potas-
sium salt; acidification of the latter with aqueous HCl
yields compounds 6 and 7. The formation of triester 6
from compound 1 in the presence of sodium metal was
reported in [2].
Methyl 2-(2-methoxy-2-oxoethyl)-4-methylfur-
an-3-carboxylate (5). Yield 6.1 g (31%), bp 120°C
(3 mm). 1H NMR spectrum, δ, ppm: 2.10 s (3H, CH3),
3.60 s (3H, CH3O), 3.75 s (3H, CH3O), 3.90 s (2H,
CH2CO), 7.10 s (1H, CH=). 13C NMR spectrum, δC,
ppm: 9.78 (CH3), 34.05 (CH2CO), 51.13 (CH3O),
52.21 (CH3O), 121.22 (C4), 139.11 (C3), 154.90 (C5),
165.00 (C=O), 169.20 (C=O). Found, %: C 56.39;
H 5.26. C10H12O5. Calculated, %: C 56.60; H 5.66.
Alkylation of dimethyl 3-oxopentanedioate (1)
(general procedure). 1,2-Dibromoethane or 1,2,3-tri-
bromopropane, 0.05 mol, was added with stirring to
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 6 2017

ISMAILOV et al.
952
Dimethyl 2,4-dihydroxy-6-(2-methoxy-2-oxo-
(C=O). Found, %: C 55.00; H 5.00. C11H12O6. Calcu-
lated, %: C 54.87; H 5.11.
The H and 13C NMR spectra were recorded from
solutions in CDCl3 on a Bruker A-300 spectrometer at
300 and 75 MHz, respectively; the chemical shifts
were measured relative to tetramethylsilane.
ethyl)benzene-1,3-dicarboxylate (6) and dimethyl
2,4-dihydroxy-6-methylbenzene-1,3-dicarboxylate
(7). A mixture of 10 g (0.05 mol) of compound 1 and
15 g of potassium carbonate in 50 mL of DMSO was
stirred for 5 h at 60–70°C. The mixture was cooled,
treated with water, and acidified with aqueous HCl.
The precipitate (a mixture of 6 and 7) was recrystal-
lized from ethanol to isolate 4.2 g (52%) of compound
1
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