Synthesis of 1,3,4,6-tetraoxo compounds

Article abstract of DOI:10.1134/S1070363216110050

The two-step method of synthesis of 1,3,4,6-tetraoxocompounds with different terminal substituents is developed. By condensation of alkyl methyl ketones with dimethyl oxalate new 1,6-dialkyl-substituted 1,3,4,6-tetraoxohexanes are obtained. The esters of 3,4,6-trioxoalkanoic acids are synthesized by the condensation reaction of alkyl acetates with dialkyl oxalates and alkyl methyl ketones. By the reaction of ethyl acetate with diethyl oxalate and methyl acetate the mixed diester of 3,4-dioxo-1,6-hexanedioic (ketipic) acid has been first prepared. Specific structural features of the synthesized compounds are discussed basing on the data of the IR, NMR, and XRD diffraction (XRD) analysis.

Full text of DOI:10.1134/S1070363216110050

ISSN 1070-3632, Russian Journal of General Chemistry, 2016, Vol. 86, No. 11, pp. 2427–2436. © Pleiades Publishing, Ltd., 2016.
Original Russian Text © P.P. Mukovoz, V.О. Koz’minykh, А.V. Gorbunova, P.А. Slepukhin, О.S. El’tsov, I.N. Ganebnykh, А.V. Kuzmin, 2016, published in
Zhurnal Obshchei Khimii, 2016, Vol. 86, No. 11, pp. 1784–1793.
Synthesis of 1,3,4,6-Tetraoxo Compounds
P. P. Mukovoza*, V. О. Koz’minykhb, А. V. Gorbunovac, P. А. Slepukhind,e,
О. S. El’tsove, I. N. Ganebnykhd,e, and А. V. Kuzminf
a Moscow Technological Institute, Orenburg Branch, pr. Pobedy 75, Orenburg, 460018 Russia
*e-mail: mpp27@mail.ru
b Perm State Humanitary Pedagogical University, Perm, Russia
c Orenburg State University, Orenburg, Russia
d I.Ya. Postovskii Institute of Organic Synthesis, Ural Branch of Russian Academy of Sciences, Yekaterinburg, Russia
e Ural Federal University named after the first President of Russia B.N. Yeltsin, Yekaterinburg, Russia
f Institute of Solid State Physics of Russian Academy of Sciences, Chernogolovka, Russia
Received April 14, 2016
Anhydroustract—The two-step method of synthesis of 1,3,4,6-tetraoxocompounds with different terminal
substituents is developed. By condensation of alkyl methyl ketones with dimethyl oxalate new 1,6-dialkyl-
substituted 1,3,4,6-tetraoxohexanes are obtained. The esters of 3,4,6-trioxoalkanoic acids are synthesized by the
condensation reaction of alkyl acetates with dialkyl oxalates and alkyl methyl ketones. By the reaction of ethyl
acetate with diethyl oxalate and methyl acetate the mixed diester of 3,4-dioxo-1,6-hexanedioic (ketipic) acid
has been first prepared. Specific structural features of the synthesized compounds are discussed basing on the
data of the IR, NMR, and XRD diffraction (XRD) analysis.
Keywords: 1,6-dialkyl-1,3,4,6-tetraoxohexanes, esters of 3,4-dihydroxy-2,4-hexadiene-1,6-dioic and
3,4-dihydroxy-6-oxo-2,4-alkadienoic acids
DOI: 10.1134/S1070363216110050
1,3,4,6-Tetraoxocarbonyl compounds are reactive
species which are used in organic synthesis, including
the synthesis of biologically active compounds [1–3].
The data on 1,3,4,6-tetracarbonyl compounds with
different terminal substituents are limited to the
methods of synthesis of 1,6-diarylsubstituted [4–8], 1-
alkyl-6-arylderivatives of 1,3,4,6-tetraoxohexane [9,
10] or the esters of 6-aryl-3,4,6-trioxohexanoic acid
[11]. The known methods are not universal and do not
have preparative value [12].
prepare 1,6-dialkyl-1,3,4,6-tetraoxohexanes or esters
of 3,4,6-trioxoalkanoic acids by one-step condensation
of two different methylenecarbonyl compounds with
dialkyl oxolates in the presence of two-fold excess of
condensing agent. Performing the reaction in two steps
with successive introduction of equimolar amounts of
different methylenecarbonyl compounds and dialkyl
oxolate was neither successful.
The formation of substantial amounts of by-
products in the one-step method is due to the reaction
of dialkyl oxolates with only one of the two methylene-
carbonyl compounds that leads to the formation of the
1,3,4,6-tetracarbonyl compounds possessing C3–C4-
axial symmetry. The presence of by-products in the
two-step method is connected with the reversibility of
the condensation reaction and the presence of both
unreacted methylenecarbonyl compounds in the
reaction mixture. Another possible reason of inap-
plicability or low efficiency of the above methods is
the accumulation of alcohol in the reaction mixture
The one-step condensation of two-fold excess of
methylenecarbonyl compounds with dialkyl oxolates
in the presence of excess of condensing agents is a
well known preparative method for the synthesis of
1,3,4,6-tetracarbonyl compounds [1, 12, 13]. This
method allows to obtain 1,6-diaryl- and 1,6-dialkyl-
1,3,4,6-tetraoxohexanes or esters of 3,4-dioxo-1,6-
hexanedioic (ketipic) acid in good yields, but it cannot
be applied to the synthesis of 1,3,4,6-tetraoxosystems
with different terminal substituents. Thus, we failed to
2427

2428
MUKOVOZ et al.
Scheme 1.
O
R1
Me
Me
R2
AlkO
OAlk
+
+
O
O
O
H
(1) AlkONa, t
(2) NaH, t
O
O
O
O
R1
R1
R2
+2H+
R2
_2Na+
_AlkOH
O
O
O
O
H
B
А
1а_1d, 2а_2d, 3а_3c
R1 = Me (1а, 1b), Et (1c, 1d), ОМе (2а, 2b, 2c, 3а, 3b), OEt (2d), R2 = Me (2а, 2d), Et (1а, 2b), Pr (1b, 1c, 2c), C5H11 (1d),
OEt (3а, 3c).
formed due to elimination of alkoxy groups. The
molecules of alcohol prevent the anhydroustraction of
proton from the methylele-active reagent by the
alkoxide anion, shifting the equilibrium to the starting
reagents. Thus, in alcohol medium, the condensation of
a methylenecarbonyl compound with dialkyl oxolates
proceeds smoothly only till the stage of formation of
1,2,4-tricarbonyl systems and does not give 1,3,4,6-
tetracarbonyl compounds [14].
synthesized in 57–68% yields (7–13% for compounds
2а–2c [15, 16]). Note that compound 2d was prepared
for the first time.
By the reaction of ethyl acetate with diethyl oxolate
and methyl acetate we have first synthesized the mixed
diester of 3,4-dihydroxy-2,4-hexadiene-1,6-dioic (3,4-
dioxo-1,6-hexanedioic) acid 3а in 61% yield (Scheme 1).
The reaction of alkyl acetates with dialkyl oxolates
affords alkyl esters of 3,4-dihydroxy-2,4-hexadiene-1,6-
dioic acid 3b, 3c in 55–67% yield (42–49% [17, 18]).
In the present work we describe a simple and
convenient method for the synthesis of 1,3,4,6-tetra-
carbonyl compounds by two-step condensation of
alkyl methyl ketones or alkyl acetates with dialkyl
oxolates in the presence of condensing agents different
in each stage. In such a method the effectiveness of the
synthesis is increased due to a decrease in the
accumulation of the alcohol in the reaction system,
which allows the preparation of 1,3,4,6-tetracarbonyl
compounds, both with identical and different terminal
substituents, in preparative yields.
Compounds 1а–1d, 2а–2d, 3а–3c are colorless
crystalline substances insoluble in water and readily
soluble in most organic solvents. Their structure was
1
determined by the methods of IR, H NMR spectro-
scopy, mass spectrometry and XRD analysis. The IR
spectra of compounds 1а–1d contain broadened bands
νОН in the range 3300–2400 cm–1, broadened bands of
oxo groups C1(6)=O of the acyl fragments at 1623–
1607 cm–1, as well as wide bands of multiple bonds at
1568–1567 cm–1, which is consistent with the enol
structure 1A (Scheme 2). Strong broadening and the
shift to the low frequencies of the bands νОН are
indicative of the presence of hydrogen bonds in the
molecules of compounds 1а–1d, while the low
frequency of the С=О groups is due to the conjugation
with the C=C bonds in the dioxodienol fragment. For
comparison, the anhydrousorption bands of the C3–C4-
axial symmetrical 1,3,4,6-tetraoxohexanes appear in
similar ranges: at 3200–3253 (ОН), 1556–1607 (С=О)
and 1556–1607 cm–1 (С=C) [13, 19, 20].
By the two-step reaction of different alkyl methyl
ketones with dimethyl oxolate we have first syn-
thesized 1,6-dialkyl-1,3,4,6-tetraoxohexanes 1а–1d in
64–83% yields. The first stage was carried out by
condensation of equimolar amounts of one alkyl
methyl ketone with dimethyl oxolate and sodium
methoxide, and the second step was performed by
adding equimolar amount of another alkyl methyl
ketone and sodium hydride to the mixture.
By the two-step reaction of different alkyl acetates
with the corresponding dialkyl oxolates and alkyl
methyl ketones the esters of 3,4-dihydroxy-6-oxo-2,4-
alkadienoic (3,4,6-trioxo-alkanoic) acids 2а–2d were
The structure of compound 1c was established by
XRD method. In the crystal compound 1c exists in the
form (2Z,4Z)-1,6-dioxo-3,4-dienol 1A (Scheme 2) with
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SYNTHESIS OF 1,3,4,6-TETRAOXO COMPOUNDS
Fig. 1. XRD structure of compound 1c with thermal ellipsoids of 50% probability.
the s-trans configuration of the С3–С4 bond (Fig. 1).
Nonhydrogen atoms of molecule 1c lie in one plane
within 0.15Å, the carbonyl groups of the acyl
fragments form with the enol hydroxy groups two six-
membered OH-chelate rings closed by intramolecular
hydrogen bonds with the OH···О=C.
the refinement with population coefficient of 0.5. The
arising disordering is, apparently, due to specific
features of the crystal packing (Fig. 2).
In chloroform solution compounds 1а–1d, as in the
solid state exist in the dienol form 1A, similar to the
C3–C4-axial symmetrical 1,3,4,6-tetraoxohexanes [13,
1
Two OH-chelate fragments in the 1,6-dioxo-3,4-
dienol motif in molecule 1c have practically equal
bond lengths [C3=O2 1.247, С3–С4 1.441, C4=C5 1.346,
С5–O1 1.334, O1–H1 0.89 Å].
19, 20]. In the H NMR spectra of compounds 1а–1d,
apart from the signals of alkyl groups, a singlet of two
olefin protons at 6.33 ppm and a broadened singlet of
two protons of the enol hydroxy groups at 14.62–
14.68 ppm are present, which confirms the structure of
tautomer 1A.
The alkyl substituents in the bis-chelate fragment
are statistically disordered between two positions with
population coefficients 0.5, therefore, the final
structure is the result of superposition of two
molecules with different orientation of the alkyl
substituents. The coordinates of the atoms, except for
the terminal groups, practically coincide. Besides,
practically equal are the coordinates of the carbon
atoms of the methylene link of the n-propyl substituent
and the methyl group of the ethyl substituent;
therefore, the total population of this position and two
protons connected with it are taken as 1, and proton
H1A located on the axis of bond С1–С6 was included in
It should be specially noted that in solutions of
compounds 1а–1d in a nonpolar solvent (chloroform)
the signals of the chemically different protons C2(5)
H
or C3(4)OH give singlets in the 1Н NMR spectrum. This
is an unexpected result since in the spectra of the
structurally similar and also having the bis-chelate
structure esters of 3,4-dihydroxy-6-oxo-2,4-alkadi-
enoic acids the C2(5)H and C3(4)OH protons are magne-
tically nonequivalent and have different chemical
shifts: 5.83–6.25 (С2Н), 6.25–7.17 (C5H), 11.52–12.18
(C3OH), 14.65–16.22 ppm (C4OH) [15, 16].
Scheme 2.
O
O
H
O
O
O
O
OH
OH
R1
R1
R2
O
R1
O
R2
R2
O
O
O
O
O
O
H
R1
R2
O
B
A
C
D
H
O
O
O
R1
R1
R2
R2
O
O
O
O
H
E
F
R1 = Me, Et, R2 = Et, Pr, C5H11 (1а, 1d), R1 = OMe, OEt, R2 = Me, Et, Pr (2а, 2d), R1, R2 = OMe, OEt (3а, 3c).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 11 2016

2430
MUKOVOZ et al.
Fig. 2. Fragment of molecular packing in the crystal of compound 1c.
Unlike the C3–C4-axial symmetrical 1,3,4,6-tetra-
Thus, in nonpolar chloroform, compounds 2а–2d, as
well as the structurally similar 1,3,4,6-tetracarbonyl
compounds 1а–1d, exist exclusively in the dioxodienol
form 2A, whereas in DMSO solution, exclusively as
the oxofuran tautomer 2D (Scheme 2), whose structure
oxohexanes, which in nonpolar chloroform exist in the
form of several minor tautomers (linear and cyclic
derivatives of ketoform 1B, Scheme 2) [13, 20],
compounds 1а–1d in chloroform solution do not form
these forms, as proved by the anhydrousence of the
1
was discussed earlier [13, 20]. Note that in the Н
1
corresponding signals in the H NMR spectra. In a
NMR spectra (CDCl3) of triketoesters 2а–2d, unlike
tetraketones 1а–1d, the chemical shifts of the proton
signals of the С2(5)Н and С3(4)OН groups are
substantially different (С2Н and C5H 0.09–0.31 ppm,
С3ОН and С4ОН 3.02–3.14 ppm), suggesting essential
difference in the magnetic surrounding (R1 = OAlk,
R2 = Alk) between the two chelate fragments of the
molecule [15, 16].
1
polar solvent (DMSO-d6), according to the H NMR
data, compounds 1а–1d exist in the equilibrium
between several forms (Scheme 2), among which the
oxofuran regioisomeric structures 1C (45–57%) and
1D (27–39%) predominate, whereas the dienol form
1A is present as a minor tautomer (14–19 %).
The structure of the cyclic regioisomers 1C and 1D
is proved by the presence in the spectrum of two
doublets at 2.87–2.88 and 2.98–3.01 ppm (J = 15.4–
16.5 Hz), corresponding to the methylene protons of
the Alk1(2)COCH2 group, the singlet of olefin proton of
the oxofuran cycle at 5.47–5.53 ppm, and a broadened
singlet of the hydroxyl proton of the hemiacetal
fragment at 7.76–7.84 ppm.
In the solid phase the structure of compounds 2а–2d
was earlier studied only by IR spectroscopy [15, 16].
To prove the structure of triketoesters 2 we determined
the structure of compounds 2а, 2b by XRD analysis.
According to XRD analysis the molecules of
compounds 2а, 2b exist in the form of (2Z,4Z)-1,6-
dioxo-3,4-dienol 2A (Fig. 3, Scheme 2), having the
structure similar to that of the known tetraketones 1
[21, 22]. Molecules 2а and 2b are planar (within
0.2 Å), the С1(6)=O carbonyl groups form with the
С3(4)OН hydroxyl groups two six-membered OH-
chelate rings closed by intramolecular hydrogen bonds
of the OH···О=C type. The chelate fragments in the
molecules of compounds 2а, 2b are turned out to the
trans-configuration with respect to each other, similar
to the known structural analogs 1 [19, 21, 22]. As
distinct from tetraketone 1c, the effect of two different
substituents (R1 = OAlk, R2 = Alk) in the molecules of
The presence of the dienol form 1A in solutions of
compounds 1а–1d in DMSO-d6 is proved by the
presence of proton signals of the alkyl groups and a
singlet of two olefin protons at 6.38–6.44 ppm. The
signals of the enol hydroxy groups cannot be observed
due to the strong broadening caused, apparently, by
fast exchange of protons with the solvent.
Earlier, we have established qualitative dynamic
prototropic ring-chain transformations of compounds
2а–2d in solutions in polar and nonpolar solvents.
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2431
SYNTHESIS OF 1,3,4,6-TETRAOXO COMPOUNDS
Fig. 3. XRD structure of compound 2a with thermal ellipsoids of 50% probability.
Fig. 4. XRD structure of compound 2b with thermal ellipsoids of 50% probability.
compounds 2а, 2b on the bis-chelate fragment is more
clearly pronounced, as proved by the values of the
bond lengths in the two OH-chelate rings (see the
table). The differences are, however, small, thus
indicating the formation of a common π-system in the
bis-chelate fragment of the molecule.
By the IR spectroscopy data, compound 3а in the
crystal, like esters 3b, 3c [17, 18], has the enol
structure. The IR spectrum of compound 3а contains a
broadened νОН band in the range 3300–2600 cm–1, the
Selected bond lengths in compounds 2а and 2b
2а
2b
In the crystal the molecules of compounds 2а, 2b
are organized in a layer packing formed due to an
extended system of intermolecular hydrogen bonds of
the type OH···О=C between the protons of the
hydroxyl groups and carbonyl oxygen of the ester
group, as well as due to weak van der Waals
interactions between the alkyl fragments.
С1=О1
С6=О5
С1–С2
С5–С6
С2=С3
С4=С5
С3–O3
С4–O4
O3–H3
O4–H4
1.228
1.246
1.454
1.444
1.340
1.352
1.346
1.334
0.89
С1=О5
С6=О3
С1–С2
С5–С6
С2=С3
С4=С5
С3–O2
С4–O4
O2–H2
O4–H4
1.226
1.246
1.456
1.450
1.348
1.357
1.343
1.333
0.85
The structure of compounds 2а–2d was also
confirmed by the data of high-resolution mass spectro-
metry obtained in the electrospray mode in acetonitrile
solution, where characteristic signals of ions [M + H]+
or [M + Na]+ as well as cluster ions [2M + H]+ and
[2M + Na]+ were observed.
1.02
0.84
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2432
MUKOVOZ et al.
Fig 5. XRD structure of compound 3b with thermal ellipsoids of 50% probability.
Fig. 6. Hydrogen bonds in the crystal of compound 3b.
band of ester carbonyl groups C1(6)=O at 1645 cm–1, a
broadened band of multiple bonds at 1590 cm–1, and
the νС–ОR band at 1182 cm–1, proving the enol structure
of the compound. Broadening of the ОН group bands
and their shift to the low-frequency field are indicative
of the presence of hydrogen bonds in the molecule of
compound 3а, and the low frequency of the carbonyl
groups, of their conjugation with the C=C bonds in the
enol fragments. Note that the corresponding anhyd-
rousorption bands of the known ketipinates 3 existing
in the solid state in form 3A (Scheme 2) appear in a
close region: 3480–3380 (ОН), 1660–1638 (С=О),
1630–1589 cm–1 (С=C), and 1194–1166 cm–1
(C–OAlk) [14, 17, 18].
in the trans-configuration to each other and are closed
by intramolecular hydrogen bonds OH···О=C. The
lengths of the double (C=C, C=O) and ordinary bonds
(C–C, C–O) in the OH-chelate fragments in compound
3b are slightly shorter (by 0.08–0.19 Å) than those in
compound 2а, formed with participation of the ester
carbonyl group of the MeOC=O fragment, which is
indicative of a stronger degree of conjugation in the bis-
chelate system of compound 3b (C1=O2 1.220, С1–С2
1.435, C2=C3 1.329, С3–O1 1.337 Å). The enol hyd-
roxyl protons in compound 3b are located at the
central oxygen atoms, as in 2а, as witnessed by the
values of bond lengths of the ketoenol fragments
(O1–H1 0.97 and O3–H3 0.89 Å).
To prove the structure of ketipinates 3 we deter-
mined the structure of compound 3b by XRD analysis
(for compound 3а we failed to prepare crystals suitable
for the XRD analysis). From XRD analysis (Fig. 5),
compound 3b in the crystal exists in the form of
symmetric (2Z,4Z)-1,6-dioxo-3,4-dienol 3A (Scheme 2).
The molecule is planar (within 0.2 Å), the six-
membered chelate cycles formed with the participation
of the ester carbonyl groups and the enol hydroxyls are
In the crystal, the molecules of compound 3b are
organized in a layer packing (Fig. 6) formed due to an
extended system of intermolecular hydrogen bonds
between the hydroxyl protons and the ester oxygens as
well as between the olefin protons and the hydroxyl
oxygens.
Earlier it was shown that compounds 3 exist in
solution in the equilibrium tautomeric forms (3A, 3E)
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SYNTHESIS OF 1,3,4,6-TETRAOXO COMPOUNDS
[14, 17], which are the enol derivatives of tetraoxo
form 3B (Scheme 2). Cyclic oxofuran tautomers,
which are typical for compounds 1, 2, were not
detected in solutions of compounds 3b, 3c.
acetonitrile and injected with the rate 240 μL/h by a
syringe pump 100 (KD Scientific Inc.). Positive ions
were registered in the electrospray mode with standard
ionic source in the range of masses 50–1300 Da using
parameters of the pre-installed method Direct Infusion
100–1000. Elemental analysis was performed on a
LEСO CHNS-932 instrument. Purity of the obtained
products was confirmed by TLC on Sorbfil UV-254
plates in the systems hexane–acetone 5 : 1; 3 : 1;
chloroform–hexane 10 : 1; chloroform.
1
From the H NMR spectroscopy data, in nonpolar
solvents compound 3а exists exclusively in the dienol
form 3A, whereas in polar solvents several equilibrium
tautomeric forms (3A, 3B, 3E, 3F, Scheme 2) are
1
present. In the H NMR spectrum of compound 3а in
CDCl3, apart from the signals of alkoxy groups, a
singlet of two olefin protons at 5.88 ppm and a
broadened singlet of two protons of the enol hydroxy
groups at 11.74 ppm are observed, corresponding to
tautomer 3A. As in compounds 1а–1d, the signals of
chemically nonequivalent protons C2(5)H or C3(4)OH
are present in the spectrum as singlets. No other equi-
librium tautomeric forms of compound 3а, or its
homologs 3b or 3c were found in the chloroform solution.
XRD analysis was performed on an automated
difractometer Xcalibur 3, ω-scanning with 1○ step,
monochoromator МоKα. For compounds 2а, 2b, 3b
empirical correction for extinction was introduced, for
compound 1c no correction was made. The structures
were determined by the direct method and refined by
the full-matrix least-squares method with respect to F2
in the anisotropic approximation for all nonhydrogen
atoms. CH hydrogen atoms were placed in the
geometrically calculated positions and refined in the
isotropic approximation, the positions of OH protons
were refined independently. All calculations were
performed using the program package Olex2 [23, 24].
1
In the H NMR spectrum in DMSO-d6 of com-
pound 3а, in addition to the signals of alkoxy groups
and the signals of form 3A [30%, C2(5)H 5.82 ppm,
C3(4)OH 11.61 ppm], the singlets of olefin protons С2Н
5.76 ppm (3F, 20%) and 5.78 ppm (3E, 15%),
methylene protons С5Н2 3.89 ppm (3F) and δ 3.92
ppm (3E), and hydroxyl protons С3ОН 11.35 (3F) and
11.52 ppm (3E) are observed, corresponding to two
regioisomeric ketoenol tautomers 3E, 3F, as well as a
singlet of methylene protons С2(5)Н2 3.82 ppm of
tautomer 3B.
Compound 1c: triclinic, P-1, Т 295(2) K, a 4.6434(9),
b 4.7505(12), c 13.583(3) Å, α 92.703(19)○, β 92.638(17)○,
γ 101.701(19)○, μ 0.091 mm–1. 2643 total reflections
(3.01○ < θ < 26.34○), 1122 independent reflections
(Rint 0.0248), including 537 with I > 2σ(I). Final
refinement parameters: R1 0.0981, wR2 0.1520 (on all
reflections), R1 0.0496, wR2 0.1388 [on reflections
with I > 2σ(I)], S 1.005.
In the mass spectra of compounds 3а–3c charac-
teristic signals of ions [M + H]+ or [M + Na]+, as well as
of cluster ions [2M + H]+ and [2M + Na]+ are observed.
Compound 2а: monoclinic, P21/c, Т 150(1) K, a
8.0551(5), b 13.3557(10), c 8.0649(6) Å, β 103.458(8)○,
μ 0.124 mm–1. 4757 total reflections (6.02○ < 2θ <
56.56○), 2096 independent reflections (Rint 0.0216),
including 2423 with I > 2σ(I). Final refinement
parameters: R1 0.0517, wR2 0.1406 (on all reflections),
R1 0.0780, wR2 0.1625 [on reflections with I > 2σ(I)],
S 1.007.
Therefore, the investigated 1,3,4,6-tetraoxo com-
pounds is a typical example of substituted polyenes.
All studied compounds exist in the planar bis-1,3-
ketoenol form with enolizable oxo groups in positions
3, 4 and s-trans arrangement of the double bonds in the
system of conjugation of the tetraoxo compound.
Compound 2b: monoclinic, P21/c, Т 120(1) K, a
10.1363(9), b 9.9888(7), c 9.4856(7) Å, β 98.458(8)○,
μ 0.115 mm–1. 3900 total reflections (5.76○ < 2θ <
56.56○), 2287 independent reflections (Rint 0.0216),
including 1579 with I > 2σ(I). Final refinement
parameters: R1 0.0817, wR2 0.1579 (on all reflections),
R1 0.0510, wR2 0.1345 [on reflections with I > 2σ(I)], S
1.001.
EXPERIMENTAL
IR spectra were taken on a Bruker Alpha IR Fourier
spectrometer in the attenuated total reflection mode
1
with ZnSe windows. H NMR spectra were registered
on a Bruker AVANCE II spectrometer (400 МHz),
internal reference tetramethylsilane. High resolution
mass spectra were recorded on a quadruple time-of-
flight mass spectrometer maXis impact HD, Bruker
Daltonik GmbH. The samples were dissolved in
Compound 3b: triclinic, P-1, Т 295(2) K, a 3.9776(8),
b 5.0316(9), c 11.646(2) Å, α 98.990(14)○, β 90.864(15)○,
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MUKOVOZ et al.
γ 103.671(15)○, μ 0.131 mm–1. 2164 total reflections
(3.55○ < θ < 28.27○), 1107 independent reflections
(Rint 0.0210), including 415 with I > 2σ(I). Final
refinement parameters: R1 0.0443, wR2 0.0811 (on all
reflections), R1 0.1016, wR2 0.0839 [on reflections
with I > 2σ(I)]. Full set of structural data is deposited
to the Cambridge Crystallographic Database Center
(CCDC 1043555, 1405972, 1406315, 1030426 for
compounds 1c, 2а, 2b, 3b, respectively).
CH2CH3, J = 7.3 Hz, form 1D, 32%), 1.10 t (3H,
CH2CH3, J = 7.5 Hz, form 1A, 17%), 2.17 s (3H, CH3,
form 1A), 2.19 s (3H, CH3, form 1C), 2.20 s (3H, CH3,
form 1D), 2.44 q (2H, CH2CH3, J = 7.5 Hz, form 1A),
2.48 q (2H, CH2CH3, J = 7.3 Hz, form 1D), 2.50 q
(2H, CH2CH3, J = 7.2 Hz, form 1C), 2.88 d, 2.98 d
(2H, CH2, J = 16.0 Hz, forms 1C, 1D), 5.52 s (1H,
CH, form 1C), 5.53 s (1H, CH, form 1D), 6.43 s (2H,
=CH, form 1A), 7.84 s (1H, OH, forms 1C, 1D).
Found, %: С 58.60; H 6.61. C9H12O4. M 184.19.
Calculated, %: С 58.69; H 6.57. M 184.19.
Synthesis of 1,6-dialkyl-1,3,4,6-tetraketones (1а–
1d), esters of 3,4,6-trioxoalkanoic (2а–2d) and 3,4-
dioxo-1,6-hexanedioic acids (3а–3c). Mixture of
50 mL of tetrahydrofuran, 2.0 g (50 mmol) of 60%
suspension of sodium hydride in mineral oil, 2.0 mL of
anhydrous methanol (for compounds 1а–1d, 2а–2c,
3b) or 2.9 mL of anhydrous ethanol (for compounds
2d, 3а, 3c) and refluxed for 30 min for the formation
of the corresponding sodium alkoxide. Then the
mixture of 5.9 g (50 mmol) of dimethyl oxolate (for
compounds 1а–1d, 2а–2c, 3b) and 4.5 mL (50 mmol)
of 2-butanone (for compounds 1а, 1c) or 5.3 mL
(50 mmol) of 2-pentanone (for compound 1b) or
7.1 mL (50 mmol) of 2-heptanone (for compound 1b)
or 4.0 mL (50 mmol) of methyl acetate (for compound
2а–2c, 3b) or the mixture of 6.8 mL (50 mmol) of
diethyl oxolate and 4.6 mL (50 mmol) of ethyl acetate
(for compounds 2d, 3а, 3c) was added and refluxed for
30 min. After that, to the reaction mixture was added
2.0 g (50 mmol) of 60% suspension of sodium hydride
in mineral oil and 3.7 mL (50 mmol) of acetone (for
compounds 1а, 1b, 2а, 2d) or 5.3 mL (50 mmol) of 2-
pentanone (for compounds 1c, 2c) or 4.5 mL
(50 mmol) of 2-butanone (for compounds 1d, 2b) or
4.0 mL (50 mmol) of methyl acetate (for compounds
3а, 3b) or 4.6 mL (50 mmol) of ethyl acetate (for
compound 3c) and refluxed for 1 h. The solvent was
removed, to the residue 100 mL of cooled 15%
hydrochloric acid was added, the formed precipitate
was filtered, dried, and crystallized from ethanol or
ethyl acetate.
(2Z,4Z)-1-Methyl-6-propyl-3,4-dihydroxy-2,4-hexa-
diene-1,6-dione (1b). Yield 6.73 g (68%); mp 69–70°С.
IR spectrum, ν, cm–1: 3300–2400 (ОH) 3101 (СН),
1607 (C=O), 1568 (C=C), 1463, 1377, 1247, 1188,
1145, 1095, 1084, 1040, 1027, 989, 900, 841. 1Н NMR
spectrum (CDCl3), δ, ppm: 0.96 t (3H, CH2CH2CH3,
J = 7.8 Hz), 1.68 m (2H, CH2CH2CH3), 2.24 s (3H,
CH3), 2.46 t (2H, CH2CH2CH3, J = 7.8 Hz), 6.33 s
(2H, =CH), 14.68 br.s (2H, OH), form 1A (100 %). 1Н
NMR spectrum (DMSO-d6), δ, ppm: 0.81 t (3H,
CH2CH2CH3, J = 7.5 Hz, form 1A, 19%), 0.84 t (3H,
CH2CH2CH3, J = 7.8 Hz, form 1C, 46%), 0.87 t (3H,
CH2CH2CH3, J = 7.8 Hz, form 1D, 34%), 1.42 m (2H,
CH2CH2CH3, form 1A), 1.58 m (2H, CH2CH2CH3,
forms 1C, 1D), 2.12 s (3H, CH3, form 1A), 2.14 s (3H,
CH3, form 1C), 2.15 s (3H, CH3, form 1D), 2.45 t (2H,
CH2CH2CH3, J = 7.8 Hz, form 1C), 2.46 t (2H,
CH2CH2CH3, J = 7.8 Hz, form 1D), 2.87 d, 3.00 d
(2H, CH2, J = 16.5 Hz, forms 1C, 1D), 5.47 s (1H,
=CH, form 1C), 5.48 s (1H, =CH, form 1D), 6.38 s
(2H, =CH, form 1A), 7.76 s (1H, OH, forms 1C, 1D).
Found, %: С 60.63; H 7.15. C10H14O4. M 198.22.
Calculated, %: С 60.59; H 7.12. M 198.22.
(2Z,4Z)-1-Ethyl-6-propyl-3,4-dihydroxy-2,4-hexa-
diene-1,6-dione (1c). Yield 7.42 g (70%); mp 103–
105°С. IR spectrum, ν, cm–1: 3300–2400 (ОH), 3098
(СН), 1609 (C=O), 1568 (C=C), 1460, 1378, 1292,
1
1144, 1095, 1058, 1000, 878, 807. Н NMR spectrum
(CDCl3), δ, ppm: 0.96 t (3H, CH2CH2CH3, J =
7.8 Hz), 1.16 t (3H, CH2CH3, J = 7.8 Hz), 1.68 m (2H,
CH2CH2CH3), 2.46 t (2H, CH2CH2CH3, J = 7.8 Hz),
2.52 q (2H, CH2CH3, J = 7.8 Hz), 6.33 s (2H, =CH),
(2Z,4Z)-1-Methyl-6-ethyl-3,4-dihydroxy-2,4-hexa-
diene-1,6-dione (1а). Yield 5.89 g (64%); mp 43–44°С.
IR spectrum, ν, cm–1: 3300–2400 br (ОH.), 3110 (СН),
1623 (C=O), 1567 (C=C), 1463, 1377, 1244, 1184,
1140, 1095, 1056, 991, 921, 895, 806. 1Н NMR
spectrum, δ, ppm: 1.16 t (3H, CH2CH3, J = 7.5 Hz),
2.24 s (3H, CH3), 2.52 q (2H, CH2CH3, J = 7.5 Hz),
6.33 s (2H, =CH), 14.62 br.s (2H, OH), form 1A
1
14.62 br.s (2H, OH), form 1A (100%). Н NMR
spectrum (DMSO-d6), δ, ppm: 0.85
t
(3H,
CH2CH2CH3, J = 7.2 Hz, form 1C, 45%), 0.90 t (3H,
CH2CH3, J = 7.2 Hz, form 1D, 39%), 0.94 t (3H,
CH2CH2CH3, J = 7.5 Hz, form 1A, 14%), 0.96 t (3H,
CH2CH3, J = 7.3 Hz, form 1D), 1.09 t (3H, CH2CH3,
J = 7.4 Hz, form 1A), 1.16 t (3H, CH2CH3, J = 7.3 Hz,
1
(100%). Н NMR spectrum (DMSO-d6), δ, ppm: 0.90 t
(3H, CH2CH3, J = 7.2 Hz, form 1C, 47%), 0.91 t (3H,
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SYNTHESIS OF 1,3,4,6-TETRAOXO COMPOUNDS
form 1C), 1.45 m (2H, CH2CH2CH3, form 1A), 1.46 m
(2H, CH2CH2CH3, form 1C), 1.61 m (2H, CH2CH2CH3,
form 1D), 2.46 t (2H, CH2CH2CH3, J = 7.2 Hz, form
1C), 2.48 t (2H, CH2CH2CH3, J = 7.2 Hz, form 1D),
2.51 q (2H, CH2CH3, J = 7.3 Hz, form 1D), 2.52 q
(2H, CH2CH3, J = 7.3 Hz, form 1C), 2.58 t (2H,
CH2CH2CH3, J = 7.5 Hz, form 1A), 2.63 q (2H,
CH2CH3, J = 7.4 Hz, form 1A), 2.87 d, 2.99 d (2H,
CH2, J = 15.6 Hz, forms C, 1D), 5.52 s (1H, =CH,
forms 1C, 1D), 6.43 s (2H, =CH, form 1A), 7.79 s
(1H, OH, forms 1C, 1D). Found, %: С 62.29; H 7.55.
C11H16O4. M 212.24. Calculated, %: С 62.25; H 7.60.
M 212.24.
spectrum, ν, cm–1: 3300–2400 (ОH), 2995 (СН3), 2911
(СН2), 2855, 1633 (C1=O), 1607 (C6=O), 1575 (C=C),
1475, 1374, 1222, 1084, 1030, 981, 908, 795, 727. Н
1
NMR spectrum (CDCl3), δ, ppm: 1.33 t (3Н,
OСН2СН3, J = 7.2 Hz), 2.25 s (3Н, СН3), 4.27 q (2Н,
OСН2СН3, J = 7.2 Hz), 5.97 s (1Н, С2Н), 6.26 s (1Н,
С5Н), 11.73 s (1Н, С3ОН), 14.75 s (1Н, С4ОН), form
1
2A (100%). Н NMR spectrum (DMSO-d6), δ, ppm:
1.13 t (3Н, OСН2СН3, J = 7.2 Hz), 2.17 s (3Н, СН3),
2.81 d, 2.87 d (2Н, С2Н2, J = 15.3 Hz), 4.00 q (2Н,
OСН2СН3, J = 7.2 Hz), 5.50 s (1Н, С5'Н), 7.84 s (1Н,
С3'ОН), form 2D (100 %). Found: m/z 201.0758 [M +
H]+. Calculated for С9Н13О5+: 201.0757.
(2Z,4Z)-1-Ethyl-6-pentyl-3,4-dihydroxy-2,4-hexa-
diene-1,6-dione (1d). Yield 9.96 g (83%); mp 40–42°С.
IR spectrum, ν, cm–1: 3300–2400 (ОH), 3098 (СН),
1615 (C=O), 1568 (C=C), 1464, 1378, 1246, 1143,
1094, 1058, 1003, 886, 810. 1Н NMR spectrum
(CDCl3), δ, ppm: 0.84 t (3H, (CH2)4CH3, J = 7.0 Hz),
1.14 t (3H, CH2CH3, J = 7.8 Hz), 1.12–1.34 m [8H,
(CH2)4CH3], 2.52 q (2H, CH2CH3, J = 7.8 Hz), 6.33 s
Methyl Ethyl (2Z,4Z)-3,4-dioxo-1,6-hexane-
dioate (3а). Yield 6.59 g (61%); mp 64–66°С. IR
spectrum, ν, cm–1: 3300–2600 (ОH), 3128 (СН), 2982,
2951, 2854, 1645 (C=O), 1590 (C=C), 1447, 1375,
1182, 1083, 1014, 829. 1Н NMR spectrum (CDCl3), δ,
ppm: 1.33 t (3Н, OСН2СН3, J = 7.6 Hz), 3.82 s (3Н,
ОСН3), 4.28 q (2Н, OСН2СН3, J = 7.6 Hz), 5.88 s
1
(2Н, =СН), 11.74 s (2Н, ОН), form 3A (100%). Н
1
(2H, =CH), 14.65 br.s (2H, OH), form 1A (100%). Н
NMR spectrum (DMSO-d6), δ, ppm: 1.19 t (3H,
CH2CH3, J = 7.3 Hz, form 3B, 35%), 1.20 t (3H,
CH2CH3, J = 7.3 Hz, forms 3E, 3F), 1.26 t (3H,
CH2CH3, J = 7.3 Hz, form 3A, 30%), 3.65 s (3H, CH3,
form 3B), 3.75 s (3H, CH3, form 3F, 20%), 3.76 s (3H,
CH3, form 3E, 15%), 3.79 s (3H, CH3, form 3A), 3.82
s (4H, СН2, form 3B), 3.89 s (2H, С5Н2, form 3F),
3.92 s (2H, С5Н2, form 3E), 4.11 q (2H, CH2CH3, J =
7.3 Hz, forms 3E, 3F), 4.12 q (2H, CH2CH3, J = 7.3
Hz, form 3B), 4.23 q (2H, CH2CH3, J = 7.3 Hz, form
3A), 5.76 s (1H, С2Н, form 3F), 5.78 s (1H, С2Н, form
3E), 5.82 s (2H, =СН, form 3A), 11.35 s (1H, С3ОН,
form 3F), 11.52 s (1H, С3ОН, form 3E), 11.61 s (2H,
ОН, form 3A). Found: m/z 217.0703 [M + H]+.
Calculated for С9Н13О6+: 217.0707.
NMR spectrum (DMSO-d6), δ, ppm: 0.88 t [3H,
(CH2)4CH3, J = 7.2 Hz, form 1C, 57%], 0.91 t [3H,
(CH2)4CH3, J = 6.0 Hz, form 1D, 27%], 0.92 t [3H,
(CH2)4CH3, J = 7.0 Hz, form 1A, 16%], 1.09 t (3H,
CH2CH3, J = 7.0 Hz, form 1A), 1.13 t (3H, CH2CH3,
J = 6.0 Hz, form 1D), 1.16 t (3H, CH2CH3, J = 7.2 Hz,
form 1C), 1.19–1.68 m [8H, (CH2)4CH3, forms 1A,
1C, 1D], 2.42–2.68 m (2H, CH2CH3, forms 1A, 1C,
1D), 2.88 d, 3.01 d (2H, CH2, J = 15.4 Hz, forms 1C,
1D), 5.51 s (1H, CH, form 1C), 5.52 s (1H, CH, form
1D), 6.44 s (2H, =CH, form 1A), 7.79 s (1H, OH,
forms 1C, 1D). Found, %: С 64.90; H 8.45. C13H20O4.
M 240.30. Calculated, %: С 64.98; H 8.39. M 240.30.
Methyl (2Z,4Z)-3,4-dihydroxy-6-oxo-2,4-hepta-
dienoate (2а). Yield 6.32 g (68%); mp 98–100°С.
Found: m/z 209.0420 [M + Na]+. Calculated for
С8Н10NaО5+: 209.0420.
Dimethyl (2Z,4Z)-3,4-dioxo-1,6-hexanedioate (3b).
Yield 5.56 g (55%); mp 120–122°С. Found: m/z
225.0370 [M + Na]+. Calculated for С8Н10NaО6+:
225.0367.
Methyl (2Z,4Z)-3,4-dihydroxy-6-oxo-2,4-octa-
dienoate (2b). Yield 5.70 g (57%); mp 76–78°С.
Found: m/z 201.0761 [M + H]+. Calculated for
С9Н13О5+: 201.0757.
Diethyl (2Z,4Z)-3,4-dioxo-1,6-hexanedioate (3c).
Yield 7.71 g (67%); mp 77–78°С. Found: m/z
253.0674 [M + Na]+. Calculated for С10Н14NaО6+: 253.
0671.
Methyl (2Z,4Z)-3,4-dihydroxy-6-oxo-2,4-nona-
dienoate (2c). Yield 6.85 g (64%); mp 67–68°С.
Found: m/z 237.0737 [M + Na]+. Calculated for
С10Н14NaО5+: 237.0733.
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MUKOVOZ et al.
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