Synthesis and Structure of Biologically Active 1,2-Bis(2-oxocycloalkyl)ethane-1,2-diones and 3,4-Dioxo-4-(2-oxocycloalkyl)butanoic Acid Esters

Article abstract of DOI:10.1134/S107036321901002X

A two-step procedure has been proposed for the synthesis of 1,2-bis(2-oxocycloalkyl)ethane-1,2-diones and 3,4-dioxo-4-(2-oxocycloalkyl)butanoic acid esters by condensation of cycloalkyl ketones with dimethyl oxalate or of alkyl acetates with dialkyl oxala

Full text of DOI:10.1134/S107036321901002X

ISSN 1070-3632, Russian Journal of General Chemistry, 2019, Vol. 89, No. 1, pp. 8–13. © Pleiades Publishing, Ltd., 2019.
Russian Text © P.P. Mukovoz, E.S. Dankovtseva, V.P. Mukovoz, V.V. Abramova, D.S. Korol’kova, A.N. Sizentsov, E.A. Danilova, 2019, published in
Zhurnal Obshchei Khimii, 2019, Vol. 89, No. 1, pp. 11–18.
Synthesis and Structure of Biologically Active
1,2-Bis(2-oxocycloalkyl)ethane-1,2-diones
and 3,4-Dioxo-4-(2-oxocycloalkyl)butanoic Acid Esters
P. P. Mukovoza*, E. S. Dankovtsevaa, V. P. Mukovoza, V. V. Abramovaa,
D. S. Korol’kovab, A. N. Sizentsovb, and E. A. Danilovac
a All-Russian Research Institute of Phytopathology, ul. Institut 5, Bol’shie Vyazemy, Moscow oblast, 143050 Russia
*e-mail: mpp27@mail.ru
b Orenburg State University, pr. Pobedy 13, Orenburg, 460018 Russia
c Ivanovo State University of Chemistry and Technology, Sheremetevskii pr. 7, Ivanovo, 153000 Russia
Received May 14, 2018; revised May 14, 2018; accepted May 20, 2018
Abstract—A two-step procedure has been proposed for the synthesis of 1,2-bis(2-oxocycloalkyl)ethane-1,2-
diones and 3,4-dioxo-4-(2-oxocycloalkyl)butanoic acid esters by condensation of cycloalkyl ketones with
dimethyl oxalate or of alkyl acetates with dialkyl oxalates and cycloalkyl ketones, respectively. The structure of
1
the synthesized compounds has been discussed on the basis of their IR, H NMR, and mass spectra, and their
antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Salmonella typhimurium strains has
been estimated.
Keywords: 1,3,4,6-tetracarbonyl compounds, cycloalkyl ketones, 1,2-bis(2-oxocycloalkyl)ethane-1,2-diones,
3,4-dioxo-4-(2-oxocycloalkyl)butanoic acid esters
DOI: 10.1134/S107036321901002X
It is known that 1,3,4,6-tetracarbonyl compounds
obtained by condensation of methylene carbonyl com-
pounds (alkyl methyl ketones or alkyl acetates) with
dialkyl oxalates (Claisen condensation) are succes-
sfully used in organic synthesis for the preparation of
practically important products and biologically active
substances [1, 2].
We failed to obtain the corresponding 1,3,4,6-tetra-
ketones by condensation of cyclopentanone or cyclo-
hexanone with dimethyl, diethyl, dipropyl, or dibutyl
oxalate under the reported conditions; obviously, the
procedures described in [3–5] are not universal. The
reactions were accompanied by tar formation, and we
succeeded in isolating from the reaction mixtures only
2-oxo-2-(2-oxocycloalkyl)acetic acids [6] that are
products of decomposition of the corresponding commercial
esters. Presumably, the efficiency of the procedures
proposed in [3, 5] is insufficient due to low reactivity
of cycloalkyl ketones in comparison to alkyl methyl
ketones and alkyl acetate (classical reagents in the
Claisen condensation), as well as due to the fact that
the synthesis is carried out in one step. Dis-advantages
of one-step methods of synthesis of 1,3,4,6-tetracar-
bonyl compounds, in particular accumulation in the re-
action system of alcohol resulting from elimination of
alkoxy groups from the reactants, as well as long re-
action time promoting formation of by-products in low-
boiling solvents, were discussed by us previously [2].
Published data on the synthesis of 1,3,4,6-tetra-
carbonyl compounds from cycloalkyl ketones as active
methylene component are limited to a few studies
where reactions of diethyl oxalate with ketones of the
terpene series (camphor, norcamphor, nopinone) have
been described [3–5]. These reactions afforded some
1,3,4,6-tetracarbonyl compounds containing cyclo-
aliphatic fragments in the tetracarbonyl moiety, 1,2-bis-
[(1R,4R)-4,7,7-trimethyl-3-oxobicyclo[2.2.1]hept-2-yl]-
ethane-1,2-dione [3–5], 1,2-bis(3-oxobicyclo[2.2.1]-
hept-2-yl)ethane-1,2-dione [5], and 1,2-bis[(1R,5R)-6,6-
dimethyl-2-oxobicyclo[3.1.1]hept-3-yl]ethane-1,2-
dione [5]. There are no published data on the synthesis
of 1,3,4,6-tetracarbonyl compounds by condensation of
other cycloalkyl ketones (e.g., cyclopentanone or cyclo-
hexanone) with dialkyl oxalates.
To eliminate the above drawbacks, we have
developed a simple and convenient two-step procedure
8

SYNTHESIS AND STRUCTURE OF BIOLOGICALLY ACTIVE
9
Scheme 1.
R2
(CH2)n
(CH2)n
O
O
O
(1) MeONa, t
(2) NaH, t
H2C
R1
MeO
R1
_3MeOH
_2H+
_2Na+
OMe +
+
O
O
O
O
R2
1a_2c
O
R1 + R2 = (CH2)m, m = 3, n = 1 (1a); R1 + R2 = (CH2)m, m = 4, n = 2 (1b); R1 = OMe, R2 = H, n = 1 (2а); R1 = OMe, R2 = H,
n = 2 (2b); R1 = OEt, R2 = H, n = 1 (2c).
for the preparation of C3–C4-axisymmetric and unsym-
metrical 1,3,4,6-tetracarbonyl compounds containing
cycloaliphatic fragments in the tetracarbonyl moiety. A
peculiar feature of the proposed procedure is the use of
a minimum amount of a relatively high-boiling solvent
(1,4-dioxane) and of different condensing agents in the
first and second steps, namely sodium alkoxide in the
first step and sodium hydride in the second step. These
conditions simultaneously ensured maintenance of a
high concentration of the reactants and reduced the
accumulation of alcohol (departing group) which
reacted with sodium hydride in the second step. A
relatively high boiling temperature of the solvent (101°C)
considerably improves the efficiency due to shortening
of the reaction time (15–20 min), which minimizes
formation of by-products [2, 7].
The two-step reactions of alkyl acetates with
dialkyl oxalates and cycloalkyl ketones afforded 29–
41% of previously unknown 3,4-dioxo-4-(2-oxocyclo-
alkyl)butanoic acid esters 2a–2c. In the first step, alkyl
acetate reacted with the corresponding dialkyl oxalate
and sodium alkoxide, and subsequent addition of
equimolar amounts of cyclopentanone or cyclo-
hexanone and sodium hydride led to the formation of
the target esters (Scheme 1).
Compounds 1a, 1b, and 2a–2c are colorless
crystalline solids that are insoluble in water and
soluble in most organic solvents. Their structure was
1
determined on the basis of IR, H NMR, and high-
resolution mass spectra.
Unlike all known tetracarbonyl compounds which
exist in crystal as dioxodienol tautomers (bis-H-
chelates), crystalline compounds 1a and 1b have
tetraketone structure 1A (Scheme 2). This follows
from their IR spectra which show absorption bands at
2971–2854 cm–1 typical of stretching vibrations of
methylene groups of the cycloaliphatic fragments and
two relatively high-frequency carbonyl bands at 1728–
1727 and 1689–1680 cm–1 due to unconjugated
C1(6)=O and C3(4)=O carbonyl groups [2, 9, 8–12]. A
strong band at 1460–1455 cm–1 corresponding to
By the two-step reactions of cycloalkyl ketones
with dimethyl oxalate we have synthesized for the first
time 1,2-bis-(2-oxocycloalkyl)ethane-1,2-diones 1a
and 1b in 34 and 27% yield, respectively (Scheme 1).
The first step was the condensation of cyclopentanone
or cyclohexanone and dimethyl oxalate (reactant ratio
1:1) in the presence of an equimolar amount of sodium
methoxide. In the second step, equimolar amounts of
the corresponding cycloalkyl ketone and sodium
hydride were added to the reaction mixture.
Scheme 2.
H
(CH2)n
O
O
(CH2)n
O
O
O
O
(CH2)n
O
O
(CH2)n
H
1A
1B
H
O
O
H
O O
O
OH
(CH2)n
(CH2)n
O
(CH2)n
(CH2)n
O
O
O
O
(CH2)n
O
1C
H
(CH2)n
1E
1D
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 1 2019

10
MUKOVOZ et al.
scissoring vibrations of the methylene groups
confirmed the presence of methylene chains closed to
form aliphtaic rings [8]. The IR spectra of 1a and 1b
contain no absorption bands in the regions 3400–2500
(νOH) and 1400–1200 cm–1 (δOH, in-plane), which
rules out enol structure of their molecules in crystal.
The tetraketone structure of 1a and 1b is also
confirmed by the absence of bands in the region 1600–
1450 cm–1 typical of the diene fragment of known
tetracarbonyl compounds in the enol form [1, 2, 8–14].
2A. The IR spectra of crystalline samples of 2a–2c
showed a broadened low-frequency OH stretching
band in the region 3400–2900 cm–1, a strong absorp-
tion band at 1201–1176 cm–1 due to in-plane bending
vibrations of the O–H groups, and bands typical of
C–H stretching vibrations of alkoxy and endocyclic
methylene groups (2956–2852 cm–1). The low
frequency and broadening of the νOH band suggests
OH···O=C intramolecular hydrogen bonding in the
dioxodienol fragment of 2a–2c with the formation of
two H-chelate rings. Structure 2A is also supported by
the presence of low-frequency ester carbonyl
stretching band at 1639–1632 cm–1 (C1=O) and
broadened band at 1553–1548 cm–1 due to the C6=O
ketone carbonyl conjugated with the diene fragment.
The band at 1129–1079 cm–1 was assigned to
stretching vibrations of the ester C–O–C group.
Similar spectral patterns were observed for structural
analogs of compounds 2a–2c, 3,4,6-trioxoalkanoic
[3300–2400 (OH), 1653–1633 (AlkOC=O), 1616–
1607 (AlkC=O), 1580–1566 cm–1 (C=C)] [1, 2] and 3,4-
dioxohexanedioic acid esters [3480–2600 (OH), 1660–
1638 (AlkOC=O), 1630–1589 (C=C), 1236–1166 cm–1
(AlkO–C)] [2, 7, 12] and 1,6-dialkyl-1,3,4,6-tetra-
ketones [3300–2400 (OH), 1623–1607 (C=O), 1568–
1557 cm–1 (C=C)] [2, 14, 15], which also have the
structure of Z,Z′-dioxodienol tautomers in crystal.
Unlike crystalline state, compounds 1a and 1b in
solution in both polar (DMSO-d6) and nonpolar
solvents (CDCl3) exist in the dioxodienol bis-OH-
chelate form 1B which is typical of tetracarbonyl
1
compounds (Scheme 2). The H NMR spectra of 1a
and 1b contain methylene proton signals of the
cycloaliphatic fragments at δ 1.90–3.00 ppm and a
singlet in the region δ 9.10–13.80 ppm due to two
magnetically equivalent C3(4)OH enol hydroxy groups
of the C3–C4-axisymmetric Z,Z′-dienol tautomer 1B. It
1
should be noted in the H NMR spectra of structurally
related 1,6-dialkyl-1,3,4,6-tetraketones, signals of the
C3(4)OH protons of the Z,Z′ tautomer were located in a
close region, at δ 14.60–14.92 ppm [2, 8–14].
There are no signals downfield from δ 15.50 ppm,
which could be assigned to E,E′-dienol tautomer 1C
(Scheme 2). This structure is untypical of all known
tetracarbonyl compounds but was identified for struc-
turally related 1,2-bis[(1R,4R)-4,7,7-trimethyl-3-oxo-
bicyclo[2.2.1]hept-2-yl]ethane-1,2-diones [3–5]. Fur-
1
According to the H NMR data (CDCl3), com-
pounds 2a–2c in nonpolar solvents are represented by
oxo tautomer 2A (17–11%) and dioxodienol structure
2B (89–83%, Scheme 3); the latter is typical of
nonpolar solutions of most known tetracarbonyl
compounds [1, 2, 12, 13, 15]. Tautomer 2B in CDCl3 is
characterized by methylene proton signals of the
cycloaliphatic fragment at δ 0.91–3.00 ppm, signals of
the alkoxy group, C2H singlet at δ 5.54–5.97 ppm, and
two signals of nonequivalent enolic C3OH and C4OH
groups at δ 11.35–11.91 and 13.09–13.67 ppm. In the
1H NMR spectra of analogs of 2a–2c, 3,4-dioxo-
hexanedioic acid esters, the C2(5)H and C3(4)OH signals
are located at δ 5.79–5.88 and 11.64–11.80 ppm, respec-
tively [2, 12]. Minor oxo tautomer 2A in CDCl3 gives
rise to signals at δ 0.85–2.90 ppm due to methylene
protons of the cycloaliphatic fragment and singlets at
δ 3.84–3.93 (C2H2) and 3.27–3.51 ppm (C5H).
1
thermore, the H NMR spectra of 1a and 1b lacks
signals in the region δ 3.00–4.00 ppm characteristic of
tetraketone structure 1A and probable keto–enol
tautomer 1D found in solution of 3,4-dioxohexanedioic
acid esters [2, 7, 12].
1
In the H NMR spectra of 1a and 1b in DMSO-d6
we observed no hemiacetal OH signal at δ 8.00–
7.00 ppm; this signal is typical of ring oxofuran
tautomer 1E present in solutions of most known
1,3,4,6-tetraketones in DMSO [2, 12, 14, 15].
The structure of 1a and 1b is also confirmed by the
high-resolution mass spectra (electrospray ionization
from acetonitrile solution) which displayed protonated
molecular ion peaks [M + H]+.
As follows from the 1H NMR spectra of
compounds 2a–2c in DMSO-d6, the major tautomer in
polar solvents is keto–enol 2C (79–56%, Scheme 3),
and structure 2D differing by the position of the enol
fragment is the minor one (21–44%). The major
Compounds 2a–2c may be regarded as intermediate
structures between their closest analogs, 3,4,6-tri-
oxoalkanoic acid esters [1, 2], and tetraketones 1
[14, 15]. Like most known tetracarbonyl compounds,
esters 2a–2c in crystal have Z,Z′-dioxodienol structure
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 1 2019

SYNTHESIS AND STRUCTURE OF BIOLOGICALLY ACTIVE
11
Scheme 3.
H
(CH2)n
O
O
(CH2)n
O
O
OAlk
OAlk
O
O
O
O
2A
(CH2)n
2B
H
O
OH
H
(CH2)n
O
O
O
O
(CH2)n
O
O
OAlk
OAlk
O
O
O
H
O
OAlk
2E
2C
2D
tautomer is characterized by signals of the C2H proton
at δ 5.64–5.85 ppm and enol C3OH proton at δ 11.90–
11.98 ppm, as well as by a singlet at δ 3.58–3.62 ppm
due to C5H. Characteristic signals of minor tautomer
2D are those of two equivalent methylene protons on
C2 (δ 3.75–3.77 ppm) and enol C4OH group (δ 8.10–
8.15 ppm). The absence of a signal at 8.00–7.00 ppm,
which could be assigned to hemiacetal hydroxy group,
excludes the presence of oxofuran tautomer 2E typical
of structurally related 3,4,6-trioxoalkanoic acid esters
in polar solvents [2, 13].
1a, 1b, and 2a with respect to Salmonella typhimu-
rium. Presumably, the antimicrobial activity of the
examined compounds is determined by the presence of
cycloaliphatic fragments in their molecules; such
fragments are also present in the molecules of some
known biologically active compounds (camphor,
jasmone, tetracycline, etc.). Compounds 1a, 2a, and 2c
containing a cyclopentane fragment showed the
highest antimicrobial activity.
In summary, we have developed a simple and
convenient two-step procedure for the synthesis of
1,3,4,6-tetracarbonyl compounds containing cyclo-
aliphatic fragments as a part of the tetracarbonyl
moiety. The procedure implies carrying out the
reaction in a minimum amount of 1,4-dioxane with the
use of different condensing agents in the first and
second steps. It makes it possible to obtain 1,3,4,6-
tetracarbonyl compounds which were previously
inaccessible by other methods. The synthesized
compounds possess antimicrobial activity which is
likely to originate from the presence of cycloaliphatic
fragments in their molecules. Compounds containing a
cyclopentanone fragment exhibit the highest
antimicrobial activity.
The mass spectra of 2a–2c showed the correspond-
ing [M + H]+ and [M + Na]+ ion peaks.
Compounds 1a, 1b, and 2a–2c were tested for anti-
microbial activity against gram-positive (Staphylo-
coccus aureus P–209) and gram-negative bacteria
(Escherichia coli M17, Salmonella typhimurium
14028S WT). It was found that the activity of 1a, 2b,
and 2c against S. aureus is comparable to the activity
of ethacridine lactate (see the table). The activity of 2a
and 2c against E. coli exceeded that of ethacridine
lactate and were comparable to that of nitrofurazone. A
similar level of activity was revealed for compounds
Antimicrobial activity (minimum inhibitory concentration, μg/mL) of compounds 1a, 1b, and 2a–2ca
Compound
St. aureus P–209
E. coli M17
2000
S. typhimurium 14028S WT
1a
1b
2a
2b
2c
500
1000
125
500
No activity
500
500
500
No activity
500
2000
No activity
1000
1000
Ethacridine lactate
Nitrofurazone
500
2000
1000
125
500
125
a
Statistically significant data with respect to control (p = 0.001).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 1 2019

12
MUKOVOZ et al.
10 min without heating. The solvent was evaporated,
EXPERIMENTAL
100 mL of cold 15% aqueous HCl was added to the
residue, and the precipitate was filtered off on cooling
and extracted with ethyl acetate on cooling. The
extract was dried over anhydrous magnesium sulfate
on cooling and evaporated, and the residue was
crystallized from ethanol or ethyl acetate.
The IR spectra of crystalline samples were recorded
on a Bruker Alpha spectrometer with Fourier
transform, equipped with a ZnSe ATR accessory
1
(incidence angle –45°). The H NMR spectra were
measured from solutions in CDCl3 and DMSO-d6 on a
Bruker Avance II spectrometer at 400 MHz relative to
tetramethylsilane as internal standard. The mass
spectra were obtained on a Bruker Daltonik MaXis
Impact HD quadrupole time-of-flight mass spectro-
meter (electrospray ionization from solutions in
acetonitrile, flow rate 240 μL/h; default parameters for
infusion analysis of small molecules; external mass
calibration according to an improved quadratic method
using an Agilent Technologies calibration solution, part
no. G1969-85000.
1,2-Bis(2-oxocyclopentyl)ethan-1,2-dione
(1a).
Yield 4.11 g (34%), mp 62–63°C. IR spectrum, ν, cm–1:
2971 (CH2, asym.), 2903 (CH2, sym.), 1727 (C1=O,
C6=O), 1680 (C3=O, C4=O), 1460 (δCH2, scissor.),
1165, 1082, 1011, 839 (C–C, skeletal). 1H NMR
spectrum, δ, ppm: in CDCl3 (1B, 100%): 1.97 m (4H,
4′-H), 2.48 t (4H, 3′-H, J = 7.5 Hz), 3.00 t (4H, 5′-H,
J = 7.5 Hz), 13.67 s (2H, OH); in DMSO-d6 (1B,
100%): 1.96 m (4H, 4′-H), 2.47 t (4H, 3′-H, J =
7.4 Hz), 2.93 t (4H, 5′-H, J = 7.4 Hz), 9.10 s (2H, OH).
Mass spectrum: m/z: 223.0967 [M + H]+; calculated for
C12H15O4: 223.0965.
The antimicrobial activity of compounds 1a, 1b,
and 2a–2c was evaluated by the serial dilution method
in meat infusion broth at a bacterial load of
5×109 CFU/mL. Each experiment was performed in
triplicate. The minimum inhibitory concentrations
were determined. The inhibitory effect was confirmed
by inoculation into solid nutrient media from each test
tube. Nitrofurazone and ethacridine lactate were used
as reference drugs. The results were statistically
processed by calculating Student t-test using XL 2012
program. The effect was considered to be reliable at
p < 0.001.
1,2-Bis(2-oxocyclohexyl)ethane-1,2-dione (1b).
Yield 3.38 g (27%), mp 18–20°C. IR spectrum, ν, cm–1:
2925 (CH2, asym.), 2854 (CH2, sym.), 1728 (C1=O,
C6=O), 1689 (C3=O, C4=O), 1455 (δCH2, scissor.),
1172, 1125, 1076, 1033, 975, 932, 886, 837 (C–C,
1
skeletal)]. H NMR spectrum, δ, ppm: in CDCl3 (1B,
100%): 1.90 m (8H, 4′-H, 5′-H), 2.41 t (4H, 6′-H, J =
7.6 Hz), 2.87 t (4H, 3′-H, J = 7.6 Hz), 13.80 s (2H,
OH); in DMSO-d6 (1B, 100%): 1.86 m (8H, 4'-H,
5′-H), 2.38 t (4H, 6′-H, J = 7.3 Hz), 2.78 t (4H, 3′-H, J
= 7.3 Hz), 9.72 s (2H, OH). Mass spectrum: m/z:
251.1279 [M + H]+; calculated for C14H19O4:
251.1278.
1,2-Bis(2-oxocycloalkyl)ethane-1,2-diones 1a and
1b and alkyl 3,4-dioxo-4-(2-oxocycloalkyl)butane-
ates 2a–2c (general procedure). A mixture of 20 mL of
1,4-dioxane, 2.0 g (50 mmol) of a 60% suspension of
sodium hydride in mineral oil, and 2.0 mL of
anhydrous methanol (in the synthesis of 1a, 1b, 2a,
and 2b) or 2.9 mL of anhydrous ethanol (in the
synthesis of 2c) was refluxed for 10 min to obtain the
corresponding sodium alkoxide. A mixture of 5.9 g
(50 mmol) of dimethyl oxalate (1a, 1b, 2a, 2b) and
4.4 mL (50 mmol) of cyclopentanone (1a) or 5.2 mL
(50 mmol) of cyclohexanone (1b) or 4.0 mL
(50 mmol) of methyl acetate (2a, 2b) or 4.6 mL
(50 mmol) of ethyl acetate (2c) was added, the mixture
was refluxed for 10 min, 2.0 g (50 mmol) of a 60%
suspension of sodium hydride in mineral oil was
added, and a mixture of 10 mL of 1,4-dioxane and
4.4 mL (50 mmol) of cyclopentanone (1a, 2a, 2c) or
5.2 mL (50 mmol) of cyclohexanone (1b, 2b) was then
added. The resulting mixture was refluxed for 5 min;
in the synthesis of 1b, the mixture was stirred for 7–
Methyl 3,4-dioxo-4-(2-oxocyclopentyl)butanoate
(2a). Yield 4.35 g (41%), mp 38–40°C. IR spectrum, ν,
cm–1: 3400–2900 br (OH), 3123 (=C–H), 2953 (CH3,
asym.), 2922 (CH2, asym.), 2852 (CH2-, sym.), 1639
(C1=O), 1548 br (C6=O), (C=C), 1443 (δCH3, asym.),
1353 (δCH3, sym.), 1181 (δC–OH, in-plane), 1079
(C–O–C, ester), 1022, 943, 921, 910, 872, 819 (C–C,
skeletal). 1H NMR spectrum, δ, ppm: in CDCl3: 1.77 m
(2H, 4′-H, 2A, 12%), 2.00 m (2H, 4′-H, 2B, 88%), 2.36
m (2H, 3′-H, 2A), 2.50 m (2H, 3′-H, 2B), 2.90 m (2H,
5′-H, 2A), 3.00 m (2H, 5′-H, 2B), 3.51 s (1H, 5′-H,
2A), 3.78 s (3H, OCH3, 2A), 3.82 s (3H, OCH3, 2B),
3.84 s (2H, 2-H, 2A), 5.97 s (1H, 2-H, 2B), 11.91 s
(1H, 3-OH, 2B), 13.38 s (1H, 4-OH, 2B); in DMSO-
d6: 1.98 m (2H, 4′-H, 2B, 56%), 2.00 m (2H, 4′-H, 2D,
44%), 2.45 m (2H, 3′-H, 2B), 2.49 m (2H, 3′-H, 2D),
2.89 m (2H, 5′-H, 2C), 2.98 m (2H, 5′-H, 2D), 3.62 m
(1H, 5-H, 2C), 3.70 s (3H, OCH3, 2C), 3.77 s (2H,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 1 2019

SYNTHESIS AND STRUCTURE OF BIOLOGICALLY ACTIVE
13
2-H, 2D), 3.80 s (3H, OCH3, forma 2D), 5.85 s (1H,
2-H, 2C), 8.10 s (1H, 4-OH, 2D), 11.90 s (1H, 3-OH,
2C). Mass spectrum, m/z: 213.0756 [M + H]+,
235.0578 [M + Na]+; calculated for C10H13O5: 213.0758.
Mass spectrum, m/z: 227.0915 [M + H]+, 249.0735
[M + Na]+; calculated for C11H15O5: 227.0914.
CONFLICT OF INTEREST
No conflict of interest was declared by the authors.
REFERENCES
Methyl 3,4-dioxo-4-(2-oxocyclohexyl)butanoate
(2b). Yield 3.05 g (27%), mp 26–28°C. IR spectrum, ν,
cm–1: 3400–2900 br (OH), 3114 (=C–H), 2955 (CH3,
asym.), 2924 (CH2-, asym.), 2854 (CH2, sym.), 1632
(C1=O), 1554 br (C6=O, (C=C), 1450 (δCH3, asym.),
1360 (δCH3, sym.), 1201 (δC–OH, in-plane), 1129
(C–O–C, ester), 1021, 977, 960, 930, 775 (C–C,
skeletal). 1H NMR spectrum, δ, ppm: in CDCl3: 0.85 m
(4H, 4′-H, 5′-H, 2A, 17%), 0.91 m (4H, 4′-H, 5′-H, 2B,
83%), 2.03 m (2H, 3′-H, 2A), 2.10 m (2H, 3′-H, 2B),
2.50 m (2H, 6′-H, 2A), 2.55 m (2H, 6′-H, 2B), 3.27 s
(1H, 5-H, 2A), 3.71 s (3H, OCH3, 2A), 3.87 s (3H,
OCH3, 2B), 3.93 s (2H, 2-H, 2A), 5.11 s (1H, 2-H,
2B), 11.35 s (1H, 3-OH, 2B), 13.09 s (1H, 4-OH, 2B);
in DMSO-d6: 0.99 m (4H, 4′-H, 5′-H, 2C, 79%), 1.12
m (4H, 4′-H, 5′-H, 2D, 21%), 2.24 m (2H, 3′-H, 2C),
2.31 m (2H, 3′-H, 2D, 2.82 m (2H, 6′-H, 2C), 2.93 m
(2H, 6′-H, 2D), 3.58 m (1H, 5-H, 2C), 3.72 s (3H,
OCH3, 2C), 3.75 s (2H, 2-H, 2D), 3.81 s (3H, OCH3,
2D), 5.82 s (1H, 2-H, 2C), 8.15 s (1H, 4-OH, 2D),
11.98 s (1H, 3-OH, 2C). Mass spectrum, m/z: 227.0914
[M + H]+, [M + Na]+; calculated for C11H15O5: 227.0914.
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Ethyl 3,4-dioxo-4-(2-oxocyclopentyl)butanoate
(2c). Yield 4.07 g (36%), mp 73–75°C. IR spectrum, ν,
cm–1: 3400–2900 br (OH), 3118 (=C–H), 2956 (CH3,
asym.), 2920 (CH2, asym.), 2856 (CH2, sym.), 1636
(C1=O), 1553 br (C6=O, (C=C), 1453 (δCH3, asym.),
1359 (δCH3, sym.), 1176 (δC–OH, in-plane), 1087
(C–O–C, ester), 1011, 965, 915, 887, 869 (C–C,
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1
skeletal). H NMR spectrum, δ, ppm: 1.19 t (3H,
CH2CH3, J = 7.4 Hz, 2A, 11%), 1.22 t (3H, CH2CH3,
J = 7.5 Hz, 2B, 89%), 1.77 m (2H, 4′-H, 2A), 2.00 m
(2H, 4′-H, 2B, 12%), 2.36 m (2H, 3′-H, 2A), 2.50 m
(2H, 3′-H, 2B), 2.90 m (2H, 5′-H, 2A), 3.00 m (2H, 5′-
H, 2B), 3.43 s (1H, 5-H, 2A), 3.87 s (2H, 2-H, 2A),
4.20 q (2H, CH2CH3, J = 7.4 Hz, 2A), 4.22 q (2H,
CH2CH3, J = 7.5 Hz, 2B), 5.54 s (1H, 2-H, 2B), 11.75
s (1H, 3-OH, 2B), 13.67 s (1H, 4-OH, 2B); in DMSO-
d6: 1.08 t (3H, CH2CH3, J = 7.3 Hz, 2C, 61%), 1.10 t
(3H, CH2CH3, J = 7.3 Hz, 2D, 39%), 1.71 m (2H,
4′-H, 2C), 1.74 m (2H, 4′-H, 2D), 2.38 m (2H, 3′-H,
2C), 2.41 m (2H, 3′-H, 2D), 2.85 m (2H, 5′-H, 2C),
2.90 m (2H, 5′-H, 2D), 3.60 m (1H, 5-H, 2C), 3.76 s
(2H, 2-H, 2D), 4.01 q (2H, CH2CH3, J = 7.3 Hz, 2C),
4.05 q (2H, CH2CH3, J = 7.3 Hz, 2D), 5.64 s (1H, 2-H,
2C), 8.13 s (1H, 4-OH, 2D), 11.97 s (1H, 3-OH, 2C).
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 1 2019