Synthesis and structure elucidation of oxidative coupling products of 2-hydroxy-1,4-naphthoquinones

Article abstract of DOI:10.1007/s11172-006-0252-9

2,3-Dihydro-3-O-(1,4-naphthoquinon-2-yl)-2-oxo-1,4-naphthoquinones are the products of oxidative coupling of substituted 2-hydroxy-1,4-naphthoquinones (regardless of the presence of peri-hydroxy groups in their structures) under the action of lead dioxide

Full text of DOI:10.1007/s11172-006-0252-9

Russian Chemical Bulletin, International Edition, Vol. 55, No. 2, pp. 301—305, February, 2006
301
Synthesis and structure elucidation of oxidative coupling products
of 2ꢀhydroxyꢀ1,4ꢀnaphthoquinones
A. Ya. Yakubovskaya,ꢀ T. Yu. Kochergina, V. A. Denisenko, D. V. Berdyshev, V. P. Glazunov, and V. Ph. Anufrievꢀ
Pacific Institute of Bioorganic Chemistry, FarꢀEastern Branch of the Russian Academy of Sciences,
1
59 prosp. 100ꢀletiya Vladivostoka, 690022 Vladivostok, Russian Federation.
Fax: +7 (423 2) 31 4050. Eꢀmail: anufriev@piboc.dvo.ru; ayakub@piboc.dvo.ru
2
,3ꢀDihydroꢀ3ꢀOꢀ(1,4ꢀnaphthoquinonꢀ2ꢀyl)ꢀ2ꢀoxoꢀ1,4ꢀnaphthoquinones are the products
of oxidative coupling of substituted 2ꢀhydroxyꢀ1,4ꢀnaphthoquinones (regardless of the presꢀ
ence of periꢀhydroxy groups in their structures) under the action of lead dioxide.
Key words: 2ꢀhydroxyꢀ1,4ꢀnaphthoquinone, 2,5(8)ꢀdihydroxyꢀ1,4ꢀnaphthoquinone,
2
,5,8ꢀtrihydroxyꢀ1,4ꢀnaphthoquinone, lead dioxide, oxidative coupling, 2,3ꢀdihydroꢀ3ꢀOꢀ
(
1,4ꢀnaphthoquinonꢀ2ꢀyl)ꢀ2ꢀoxoꢀ1,4ꢀnaphthoquinone, density functional theory.
The isolation of islandoquinone (1a) from Cetraria
islandica lichen has been reported rather recently. Comꢀ
hydroxynaphthazarin 2a under the action of PbO in aceꢀ
tic acid. This reaction has been used previously in the
2
3
1
pound 1a is binaphthazarin of the new structural type in
synthesis of binaphthoquinones 3a,b in which the Q2H
which the 2,3ꢀdihydroꢀ1,4ꢀnaphthoquinonoid (Q2H) and
fragment is linked with the 1,2ꢀnaphthoquinonyl subꢀ
stituent (Q1,2) through the ether bond. In this case,
4
1
,4ꢀnaphthoquinonoid (Q1,4) fragments are linked through
the ether bond. The structure of biquinone 1a was deterꢀ
lapachol (2b) and lawsone derivative 2c, respectively, were
the initial hydroxynaphthoquinones. Chemical methods
were used to determine the structure of the Q2H fragment
of biquinones 3a,b. The choice between the Q1,4 fragment
and alternative Q1,2 was made (in favor of the latter) on
1
mined from the data of UV and IR spectroscopy, H and
13
C NMR spectroscopy, and mass spectrometry. To reꢀ
fine some structural features of islandoquinone, its diꢀ
2
desoxy analog 1b was synthesized. The key step in the
4
synthesis of binaphthazarin 1b is the oxidative coupling of
the basis of the UV spectral data.
Since the general structure of the Q1,2—Q2H type was
ascribed to binaphthoquinones 3a,b and that of the
Q1,4—Q2H type was ascribed to binaphthazarins 1a,b, a
question arises about the influence of structural features
of the starting 2ꢀhydroxyꢀ1,4ꢀnaphthoquinones on the
structures of their oxidative coupling products.
To answer this question, we synthesized and studied
the structures of the oxidative coupling products of
2
ꢀhydroxyꢀ1,4ꢀnaphthoquinones with and without the
hydroxy group in the periꢀposition. The radical alkylation
of 2ꢀhydroxyꢀ (4a), 2,5ꢀdihydroxyꢀ (4b), and 2,8ꢀdiꢀ
hydroxyꢀ1,4ꢀnaphthoquinones (4c) under the action of
propionyl peroxide under the conditions of its thermal
decomposition afforded ethyllawsone 2d and the correꢀ
sponding hydroxyethyljuglones 2e,f (Scheme 1).
Compounds 2d—f underwent oxidative coupling unꢀ
der the action of lead dioxide in acetic acid. The strucꢀ
tures of the synthesized products were studied by UV and
1
13
IR spectroscopy, H and C NMR spectroscopy, mass
spectrometry, and quantum chemical methods.*
1
2
: R = OH (a), H (b)
: R = Et, R2 = OH (a); R1 = CH CH=CMe , R = H (b);
1
2
* Instability of the binaphthoquinones under study in the solid
state impedes analyses of their structures by the Xꢀray diffracꢀ
tion method.
2
2
R1 = nꢀC H , R = H (c)
2
5
11
3
: R = CH CH=CMe (a), nꢀC H (b)
2 2 5 11
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 294—298, February, 2006.
066ꢀ5285/06/5502ꢀ0301 © 2006 Springer Science+Business Media, Inc.
1

302
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 2, February, 2006
Yakubovskaya et al.
Scheme 1
1
2
1
2
R
R
= R = H (4a, 2d); R = OH, R = H (4b, 2e);
1
2
= H, R = OH (4c, 2f)
1
The mass spectra and H NMR spectra indicate that
the structures of the oxidative coupling products of 2ꢀhydrꢀ
oxyꢀ1,4ꢀnaphthoquinones 2d—f are dimeric. The IR specꢀ
tra of these compounds contain absorption bands of the
carbonyl groups of the quinonoid and conjugated with the
aromatic ring dihydroquinonoid fragments (see Experiꢀ
mental), absorption bands of the free C=O groups at
752—1748 cm–1, and the bands at 1287—1231 cm , the
–1
1
latest indicate that the structures of the compounds under
1
R = R2 = H (с); R1 = OH, R = H (d); R1 = H, R2 = OH (e)
2
5
study contain the ether bond. These data along with
1
,2,6,7
literature analogies
suggest that the structures of the
calculations, ∆E
8.84 kcal mol , and ∆E1e,3e ≈ 15.02 kcal mol–1.* Such a
high difference in total energies assumes the predominant
formation of products 1c—e in the reaction (according to
the calculations, the content of products 3c—e in the
≈ 17.57 kcal mol–1, ∆E1d,3d
≈
1
c,3c
products contain the 2,3ꢀdihydroꢀ2ꢀoxoꢀ1,4ꢀnaphthoꢀ
quinonoid fragment. Thus, the compounds synthesized
by the oxidative coupling of substrates 2d—f are biquinones
in which the naphthoid and 2,3ꢀdihydroꢀ1,4ꢀnaphthoꢀ
quinonoid fragments are linked through the ether bond.
The presence of the signal from the proton of the
periꢀhydroxy group at the C(5´) atom of the quinonoid
–
1
2
–
12
–22
reaction mixture is 10 —10 %).
The quantum chemical PBE/3zꢀGIAO//B3LYP/6ꢀ31
calculations of the NMR shielding constants showed that
the difference in the CS of signals from the protons of the
periꢀhydroxy groups at the C(5´) atom of the quinonoid
fragment and at the C(5) atom of the dihydroquinonoid
fragment in compound 1d is 0.65 ppm, which agrees well
with the experimental value of the relative CS in the
1
fragment (δ 12.26) in the H NMR spectrum of the
biquinone synthesized from hydroxyethyljuglone 2e indiꢀ
cates that this fragment has the Q1,4 structure and the
whole compound has a structure of 1d. In the case of
alternative product 3d, the signal from the proton of the
periꢀhydroxy group at the C(5´) atom in the Q1 fragment
,2
1
8
H NMR spectrum (∆δ 0.75).
would be observed at δ ∼ 9.5.
In the 1H NMR spectrum of the product prepared
The total energy, which was calculated by us for
the earlier determined structure of biquinone 1b, is by
27.39 kcal mol lower than the total energy of the corꢀ
from hydroxyethyljuglone 2f, the chemical shift (CS) of
the signal from the proton of the periꢀhydroxy group of
the quinonoid fragment at the C(8) atom is observed at δ
–
1
∼
responding structure of the Q1,2—Q2H type. This indicates
that the formation of a product of the Q1,4—Q2H type is a
general rule for oxidative coupling reactions of compounds
of this type.
Taking into account the structural similarity of
naphthoquinone 2d, lapachol (2b), and lawsone derivaꢀ
tive 2c, one can propose the structures for their oxidative
coupling products. According to the quantum chemical
calculations, the differences between the total energies of
molecules 3a,b and the corresponding structures of the
1.89 and is not characteristic.2,8 The complete analysis
1
of longꢀrange correlations in 2D HMBC experiments
13
made it possible to assign signals in the C NMR spectra
and make a choice between two alternative structures 3e
and 1e in favor of the latter.
To determine the preferential direction of dimerizaꢀ
tion, we performed the quantum chemical* conformaꢀ
tional analysis of compounds 1c—e and 3c—e due to which
the relative energies ∆E1x,3x were estimated (∆E1x,3x
=
–
1
Q1,4—Q2H type are 17.77 and 17.73 kcal mol , respecꢀ
E3x – E1x; x = c—e). According to the DFTꢀPBE/3z
*
The detailed discussion of this problem is beyond the topic of
* The additional theoretical analysis showed that the total Gibbs
the present work and will be given elsewhere. For description of
the quantum chemical calculations, see Experimental.
energies (∆G ) for the indicated structures only insignificantly
0
(by 1—6%) differ from the calculated relative energies (∆Е ).
0

Oxidative coupling of hydroxynaphthoquinones
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 2, February, 2006
303
tively. The ∆E values indicate that the structures of
biquinones 3a,b proposed earlier are improbable and
should be revised in favor of 2,3ꢀdihydroꢀ3ꢀ[(3ꢀmethylbutꢀ
to 2.5 and 10.0 Hz. Mass spectra (EI) were obtained on an
LKBꢀ9000S instrument with direct injection of a sample at an
energy of ionizing electrons of 70 eV. The reaction course and
purity of the synthesized compounds were monitored by TLC on
4
2
ꢀenyl)ꢀ1,4ꢀnaphthoquinonꢀ2ꢀyloxy]ꢀ3ꢀ(3ꢀmethylbutꢀ2ꢀ
enyl)ꢀ2ꢀoxoꢀ1,4ꢀnaphthoquinone (1f) and 2,3ꢀdihydroꢀ
ꢀ(3ꢀpentylꢀ1,4ꢀnaphthoquinonꢀ2ꢀyloxy)ꢀ2ꢀoxoꢀ3ꢀpenꢀ
tylꢀ1,4ꢀnaphthoquinone (1g).
Merck 60Fꢀ254 plates. The R values were determined in a hexꢀ
f
ane—acetone (3 : 1) system. Individual compounds were isoꢀ
lated from mixtures of the reaction products using preparative
thinꢀlayer chromatography (PTLC) on plates (20×20 cm) with
3
+
9
the nonfixed 5—40ꢀµm silica gel (H form) layer. The yields of
the prepared compounds were not optimized. The starting
1
0
2
ꢀhydroxyꢀ1,4ꢀnaphthoquinone (4a), 2,5ꢀdihydroxyꢀ1,4ꢀ
1
1
naphthoquinone (4b), and 2,8ꢀdihydroxyꢀ1,4ꢀnaphthoquinone
4c) were synthesized according to known procedures. The
1
1
(
geometries of compounds 1b—g and 3a—e were optimized by
the density functional theory (DFT) with the PBE correlation
1
2
functional in the triplyꢀsplit valence basis set of atomic orbitꢀ
1
3
als (3z) using the PRIRODA program (DFTꢀPBE/3z). To
estimate relative energies (∆E), isomers characterized by the
lowest total energy were selected of all possible conformations of
compounds 1b—g and 3a—e differing in mutual orientation of
the Q2H and Q1,2, Q1,4 fragments and arrangement of the alkyl
substituents relatively to these fragments. The relative energy for
each compound was calculated with account for corrections to
zeroꢀpoint vibrational energies (ZPE) (∆Е = Etot(Q1,2—Q2H) –
R = CH CH=CMe (f), nꢀC H (g)
2
2
5 11
Biquinones 1c—g are probably the recombination
products of radicals of the A and B types formed upon
hydrogen atom abstraction from the starting substrates
2
b—f (Scheme 2).
Etot(Q1,4—Q2H), where Etot = E + ZPE are the total energies,
0
Thus, the products of oxidative coupling of 3ꢀethylꢀ2ꢀ
and E are the total electronic energies). Relative CS were calꢀ
0
hydroxyꢀ (2d), 3ꢀethylꢀ2,5ꢀdihydroxyꢀ (2e), and 3ꢀethylꢀ
,8ꢀdihydroxyꢀ1,4ꢀnaphthoquinones (2f) under the acꢀ
culated using the PRIRODA program by the DFT method with
the PBE functional in the triplyꢀsplit valence basis set of Gaugeꢀ
invariant atomic orbitals (GIAO) in geometries optimized by
2
tion of PbO in acetic acid, as well as those of described
2
2
14
hydroxynaphthazarin 2a and hydroxyꢀ1,4ꢀnaphthoꢀ
quinones 2b,c, are the corresponding biquinones 1b—g
the GAMESS program package using the DFT method with
4
15
the B3LYP exchangeꢀcorrelation functional in the 6ꢀ31G baꢀ
sis set (PBE/3zꢀGIAO//B3LYP/6ꢀ31 calculations).
containing the 1,4ꢀnaphthoquinonoid fragment.
CꢀAlkylation of hydroxynaphthoquinones 4a—c with propionyl
peroxide (general procedure). Propionyl peroxide was added
dropwise to a boiling solution of substrate 4a—c (1.0 mmol) in
Experimental
t
Bu OH (30 mL), monitoring the reaction course by TLC. The
Melting points of the synthesized compounds were deterꢀ
mined on a Boetius apparatus and are uncorrected. IR spectra
were recorded on a Bruker Vector 22 FTIR spectrometer in
CDCl and CCl . UV spectra were measured in a Cecil CE 7200
reaction was stopped when the conversion reached ∼ 80%. The
solvent was removed in vacuo, and the residue was chromatoꢀ
graphed by PTLC in a hexane—acetone (3 : 1) system.
3ꢀEthylꢀ2ꢀhydroxyꢀ1,4ꢀnaphthoquinone (2d) was synthesized
by the ethylation of lawsone (4a). The yield was 155 mg (77%),
3
4
spectrophotometer in hexane in quartz cells with a layer thickꢀ
ness of 1.0 mm. NMR spectra were detected on Bruker Avance
R 0.43, m.p. 134—137 °C (cf. Ref. 16: m.p. 137.5—138.5 °C).
f
1
13
–1
DPXꢀ300 (300.13 ( H) and 75 MHz ( C)) and Bruker Avance
IR (CCl ), ν/cm : 3406 m (βꢀOH); 1661 vs, 1654 vs (C=O);
4
1
13
DRXꢀ500 (500.13 ( H) and 125 MHz ( C)) spectrometers in
acetoneꢀd6 and CDCl using Me Si as internal standard. The
1623 vw, 1596 s (C=C). UV (hexane), λmax/nm: 241, 250, 271,
1
280, 327, ∼ 380. H NMR (300 MHz, CDCl ), δ: 1.15 (t, 3 H,
3
4
3
2
D COSYꢀ45, HSQC, and HMBC experiments were carried
Me, J = 7.6 Hz); 2.63 (q, 2 H, CH , J = 7.6 Hz); 7.34 (s, 1 H,
2
out according to standard procedures at room temperature. The
HMBC experiments were conducted with optimization for the
longꢀrange spinꢀspin coupling constant (SSCC) values equal
βꢀOH); 7.67, 7.75 (both td, 1 H each, H(6) and H(7), J1 =
7.5 Hz, J = 1.5 Hz); 8.07, 8.12 (both dd, 1 H each, H(8) and
2
1
H(5), J = 7.5 Hz, J = 1.5 Hz). H NMR (acetoneꢀd ), δ: 1.10
1
2
6
Scheme 2

304
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 2, February, 2006
Yakubovskaya et al.
(
t, 3 H, Me, J = 7.5 Hz); 2.58 (q, 2 H, CH , J = 7.5 Hz); 7.79,
and H(7)); 8.03 (dd, 1 H, H(8´), J = 8.1 Hz, J = 1.4 Hz); 8.22
2
1
2
13
7
1
7
.85 (both td, 1 H each, H(6) and H(7), J1 = 7.6 Hz, J2
=
(m, 1 H, H(5)); 8.41 (m, 1 H, (H8)). C NMR (125 MHz), δ:
7.5 (C(10)); 12.4 (C(10´)); 17.5 (C(9´)); 31.0 (C(9)); 93.2 (C(3));
126.2 (C(8´)); 126.5 (C(5´)); 128.4 (C(5)); 129.0 (C(8));
130.6 (C(8´a)); 131.6 (C(4´a)); 132.9 (C(6´)); 133.0 (C(8a));
134.0 (C(4a)); 134.4 (C(7´) and C(3´)); 134.8 (C(7)); 136.1
(C(6)); 150.8 (C(2´)); 180.6 (C(1)); 182.3 (C(4´)); 184.3 (C(2));
.5 Hz); 8.04, 8.07 (both dd, 1 H each, H(8) and H(5), J =
1
13
.6 Hz, J = 1.5 Hz); 9.48 (br.s, 1 H, βꢀOH). C NMR (75 MHz,
2
CDCl ), δ: 12.6 (C(10)); 16.7 (C(9)); 125.9 (C(3)); 126.0 (C(8));
3
1
(
26,7 (C(5)); 129.5 (C(8a)); 132.8 (C(7)); 133.0 (C(4a)); 134.8
C(6)); 152.7 (C(2)); 181.5 (C(1)); 184.5 (C(4)). Mass specꢀ
trum, m/z (Irel (%)): 203 [M + 1]+ (20), 202 [M]+ (100), 201
22), 190 (17), 174 (11), 173 (13).
ꢀEthylꢀ2,5ꢀdihydroxyꢀ1,4ꢀnaphthoquinone (2e) was syntheꢀ
sized by the ethylation of 2ꢀhydroxyjuglone (4b). The yield was
184.2 (C(1´)); 189.1 (C(4)). Mass spectrum, m/z (I (%)):
rel
+
(
402 [M] (12), 203 (22), 202 (100), 201 (57), 190 (19), 173
3
(24), 172 (31).
3ꢀ(3ꢀEthylꢀ5ꢀhydroxyꢀ1,4ꢀnaphthoquinonꢀ2ꢀyloxy)ꢀ3ꢀethylꢀ
2,3ꢀdihydroꢀ5ꢀhydroxyꢀ2ꢀoxoꢀ1,4ꢀnaphthoquinone (1d) was synꢀ
thesized by the oxidative coupling of substrate 2e. The yield was
–
1
1
3
33 mg (61%), R 0.37, m.p. 172—174 °C. IR (CCl ), ν/cm :
f
4
397 m (βꢀOH); 1659 s, 1624 s (C=O); 1599 w, 1576 vw (C=C).
1
UV (hexane), λmax/nm: 205, 244, 370, 430, ∼ 460. H NMR (300
93 mg (43%), R 0.30, m.p. 80—85 °C. Found (%): C, 66.15;
f
MHz, CDCl , 40 °C), δ: 1.16 (t, 3 H, Me, J = 7.6 Hz); 2.61 (q,
H, 4.42. C H O . Calculated (%): C, 66.36; H, 4.18. IR (CCl ),
3
24 18
8
4
–
1
2
1
7
H, CH , J = 7.6 Hz); 7.27 (dd, 1 H, H(6), J = 8.0 Hz, J =
ν/cm : 1750 m, 1702 s, 1656 s, 1629 vs (C=O); 1598 m, 1578 w
(C=C). UV (hexane), λmax/nm: 265, 290, 369, 440, 480.
2
1
2
.2 Hz); 7.41 (s, 1 H, C(2)OH); 7.52 (t, 1 H, H(7), J = 8.0 Hz);
.63 (dd, 1 H, H(8), J = 8.0 Hz, J = 1.2 Hz); 12.49 (s, 1 H,
1
H NMR (300 MHz, CDCl ), δ: 1.08, 1.28 (both t, 3 H each,
1
2
3
13
C(5)OH). C NMR (75 MHz, CDCl , 40 °C), δ: 12.6 (C(10));
Me, J = 7.5 Hz); 2.16 (m, 2 H, CH ); 2.82 (q, 2 H, CH , J =
3
2
2
1
6.2 (C(9)); 114.6 (C(4a)); 119.1 (C(6)); 125.6 (C(3)); 126.2
7.5 Hz); 7.21 (dd, 1 H, H(6´), J = 8.2 Hz, J = 1.2 Hz); 7.26
1 2
(
C(8)); 129.5 (C(8a)); 134.9 (C(7)); 153.4 (C(2)); 161.4 (C(5));
(dd, 1 H, H(8´), J = 7.5 Hz, J = 1.2 Hz); 7.41 (t, 1 H, H(7´),
1 2
1
2
80.8 (C(1)); 190.7 (C(4)). Mass spectrum, m/z (I (%)):
J = 7.9 Hz); 7.46 (dd, 1 H, H(6), J = 8.2 Hz, J = 1.2 Hz); 7.79
(t, 1 H, H(7), J = 7.9 Hz, J = 8.2 Hz); 7.95 (dd, 1 H, H(8),
1 2
rel
1 2
20 [M + 2] (5), 219 [M + 1]+ (54), 218 [M]+ (100), 190
+
(
5), 175 (7).
ꢀEthylꢀ2,8ꢀdihydroxyꢀ1,4ꢀnaphthoquinone (2f) was syntheꢀ
sized by the ethylation of 3ꢀhydroxyjuglone (4c). The yield was
J1 = 1.3 Hz, J2 = 7.5 Hz); 11.50, 12.26 (both s, 1 H each,
+
3
αꢀOH). Mass spectrum, m/z (I (%)): 435 [M + 1] (5), 434
rel
+
[M] (14), 406 (2), 391 (3), 219 (17), 218 (100), 199 (8), 190
–
1
1
3
(
(
70 mg (78%), R 0.38, m.p. 140—143 °C. IR (CCl ), ν/cm
:
(9), 189 (10), 175 (38).
f
4
425 m (βꢀOH); 1654 m, 1628 sh.s (C=O); 1601 w, 1577 w
3ꢀ(3ꢀEthylꢀ8ꢀhydroxyꢀ1,4ꢀnaphthoquinonꢀ2ꢀyloxy)ꢀ3ꢀethylꢀ
2,3ꢀdihydroꢀ8ꢀhydroxyꢀ2ꢀoxoꢀ1,4ꢀnaphthoquinone (1e) was synꢀ
thesized by the oxidative coupling of substrate 2f. The yield was
1
C=C). UV (hexane), λmax/nm: ∼ 220, ∼ 245, 282, 413. H NMR
300 MHz, CDCl ), δ: 1.14 (t, 3 H, Ме, J = 7.6 Hz); 2.61 (q,
3
2
2
7
H, CH , J = 7.6 Hz); 7.18 (dd, 1 H, H(5), J = 7.6 Hz, J =
80 mg (37%), R 0.31, m.p. 187—192 °C. Found (%): C, 66.28;
2
1
2
f
.2 Hz); 7.23 (s, 1 H, C(2)OH); 7.60 (t, 1 H, H(6), J = 7.6 Hz);
.64 (dd, 1 H, H(7), J = 7.6 Hz, J = 2.2 Hz); 11.07 (s, 1 H,
H, 4.25. C H O . Calculated (%): C, 66.36; H, 4.18. IR (CCl ),
2
4
18
8
4
–
1
ν/cm : 1752 m, 1710 s, 1656 sh.s, 1628 vs (C=O); 1595 s, 1574
m (C=C). UV (ethanol), λmax/nm: 230, 284, 400. H NMR
1
2
13
1
αꢀOH). C NMR (75 MHz, CDCl , 40 °C), δ: 12.5 (C(10));
3
1
6.8 (C(9)); 113.0 (C(8a)); 119.6 (C(5)); 123.0 (C(7)); 127.3
(500 MHz, CDCl ), δ: 1.08 (t, 3 H, Me, J = 7.5 Hz); 1.26 (t,
3
(
C(3)); 132.9 (C(4a)); 137.5 (C(6)); 152.4 (C(2)); 161.2 (C(8));
3 H, Me, J = 7.6 Hz); 2.14 (q, 2 H, CH , J = 7.5 Hz); 2.82 (q,
2
1
[
83.6 (C(1)); 184.9 (C(4)). Mass spectrum, m/z (I (%)): 219
2 H, CH , J = 7.6 Hz); 7.08 (d, 1 H, H(7´), J = 8.1 Hz); 7.44
rel
2
1
M + 1] (22), 218 [M]+ (100), 203 (9), 189 (11), 176 (11), 175
+
(d, 1 H, H(7), J = 8.1 Hz); 7.54 (t, 1 H, H(6´), J = 8.1 Hz);
1
(
33), 163 (7).
7.62 (dd, 1 H, H(5´), J = 7.6 Hz, J = 1.2 Hz); 7.76 (dd, 1 H,
1
2
Oxidative coupling of hydroxyethylnaphthoquinones 2d—f.
Freshly prepared PbO2 (96 mg, 0.4 mmol)17 was added with
vigorous stirring to a solution of hydroxyethylnaphthoquinone
H(5), J = 7.6 Hz, J = 1.2 Hz); 7.84 (t, 1 H, H(6), J = 8.1 Hz);
1 2
10.83, 11.89 (both s, 1 H each, C(8´)OH and C(8)OH).
1
3
C NMR (125 MHz), δ: 7.6 (C(10)); 12.3 (C(10´)); 17.7
2
d—f (0.3 mmol) in glacial acetic acid (2 mL) heated to the
(C(9´)); 31.4 (C(9)); 93.4 (C(3)); 114.1 (C(8´a)); 117.0 (C(8a));
119.6 (C(5´)); 120.6 (C(5)); 124.0 (C(7´)); 124.7 (C(7)); 132.2
(C(4´a)); 134.0 (C(4a)); 135.9 (C(3´)); 137.3 (C(6´)); 139.0
(C(6)); 151.0 (C(2´)); 161.8 (C(8´)); 164.6 (C(8)); 183.2 (C(4´));
184.4 (C(1)); 184.8 (C(2)); 186.5 (C(1´)); 188.3 (C(4)). Mass
boiling temperature. The reaction mixture was vigorously stirred
for 3—5 min, cooled, and filtered. The filtrate was evaporated at
temperatures <70 °C, and the residue was diluted with water
(
30 mL) and extracted with Et O (3×10 mL). The organic layer
2
+
+
was dried with Na SO4 and concentrated in vacuo, and the
resulting residue was chromatographed in hexane—acetone
spectrum, m/z (I (%)): 435 [M + 1] (8), 434 [M] (18), 433
2
rel
+
[M – 1] (9), 406 (24), 405 (19), 219 (17), 218 (100), 217 (85),
(
4 : 1) and then benzene—hexane (2 : 1) systems.
ꢀ(3ꢀEthylꢀ1,4ꢀnaphthoquinonꢀ2ꢀyloxy)ꢀ3ꢀethylꢀ2,3ꢀdiꢀ
216 (10), 188 (18).
3
hydroꢀ2ꢀoxoꢀ1,4ꢀnaphthoquinone (1c) was synthesized by the
oxidative coupling of substrate 2d. The yield was 109 mg (54%),
Rf 0.27, m.p. 65—69 °C. Found (%): C, 71.38; H, 4.80.
C H O . Calculated (%): C, 71.64; H, 4.51. IR (CDCl ),
This work was financially supported in part by
the Council on Grants of the President of the Russian
Federation (Program of State Support for Leading Sciꢀ
entific Schools of the Russian Federation, Grant
NSh 1237.2003.3), the FarꢀEastern and Siberian Branches
of the Russian Academy of Sciences (Initiative Project
No. 06ꢀIIꢀSOꢀ05ꢀ020), and the Presidium of the Russian
Academy of Sciences (Program "Molecular and Cell Bioꢀ
logy," Grant 06ꢀIꢀP10ꢀ019).
2
4
18
6
3
–
1
ν/cm : 1748 w, 1702 s, 1651 vs (C=O); ∼ 1605 m, 1595 s,
1
3
7
580 w (C=C). UV (hexane), λmax/nm: 230, 250, 260, 280, 340,
1
90. H NMR (500 MHz, CDCl ), δ: 1.08 (t, 3 H, Me, J =
3
.5 Hz); 1.26 (t, 3 H, Me, J = 7.6 Hz); 2.13 (m, 2 H, CH ); 2.84
2
(
q, 2 H, CH , J = 7.6 Hz); 7.51 (td, 1 H, H(6´), J = 7.6 Hz, J =
2
1
2
1
.3 Hz); 7.64 (m, 2 H, H(5´) and H(7´)); 7.93 (m, 2 H, H(6)

Oxidative coupling of hydroxynaphthoquinones
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 2, February, 2006
305
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Received August 4, 2005;
in revised form December 24, 2005