Cycloacylation of chloro-substituted hydroquinone dimethyl ethers with dichloromaleic anhydride

Article abstract of DOI:10.1007/s11172-016-1402-3

Under the drastic conditions of Zahn—Ochwat cycloacylation of 2-chloroand 2,3-dichlorohydroquinones with dichloromaleic anhydride (a melt of anhydrous AlCl₃ and NaCl, 185—195 °C), the substrates undergo various degrees of disproportionation, which reduces the yields of the target triand tetrachloronaphthazarins. Quantum chemical calculations showed that the cycloacylation in question proceeds as a double aromatic electrophilic substitution of the vicinal protons with the corresponding oxocarbenium ions (acylium cations).

Full text of DOI:10.1007/s11172-016-1402-3

Russian Chemical Bulletin, International Edition, Vol. 65, No. 4, pp. 993—1003, April, 2016
993
Cycloacylation of chloroꢀsubstituted hydroquinone dimethyl ethers
with dichloromaleic anhydride
V. L. Novikov, N. N. Balaneva, O. P. Shestak, V. Ph. Anufriev, and V. P. Glazunov
G. B. Elyakov Pacific Institute of Bioorganic Chemistry, FarꢀEastern Branch of the Russian Academy of Sciences,
159 prosp. 100 let Vladivostoku, 690022 Vladivostok, Russian Federation.
Fax: +7 (423) 231 4050. Eꢀmail: shestak@piboc.dvo.ru
Under the drastic conditions of Zahn—Ochwat cycloacylation of 2ꢀchloroꢀ and 2,3ꢀdiꢀ
chlorohydroquinones with dichloromaleic anhydride (a melt of anhydrous AlCl3 and NaCl,
185—195 °C), the substrates undergo various degrees of disproportionation, which reduces the
yields of the target triꢀ and tetrachloronaphthazarins. Quantum chemical calculations showed
that the cycloacylation in question proceeds as a double aromatic electrophilic substitution of
the vicinal protons with the corresponding oxocarbenium ions (acylium cations).
Key words: chlorohydroquinones, dichloromaleic anhydride, cycloacylation, Zahn—Ochwat
reaction, aromatic electrophilic acylation, chloronaphthazarins, disproportionation, homolysis,
heterolysis, quantum chemical calculations.
2,3,6ꢀTrichloroꢀ and 2,3,6,7ꢀtetrachloroꢀ5,8ꢀdihydrꢀ
oxyꢀ1,4ꢀnaphthoquinones (chloronaphthazarins 1 and 2)
are convenient starting compounds in the synthesis of sea
urchin pigments such as spinochrome D (3) and spinoꢀ
chrome E (4), respectively. The latter can be obtained
from compounds 1 and 2 in two steps: via nucleophilic
substitution of chlorine atoms with methoxy groups and
subsequent cleavage of the corresponding methyl ethers 5
and 6 upon treatment with acids (Scheme 1).
This synthetic pathway of metabolites 3 and 4 is apꢀ
parently the shortest from all the possible approaches.
Polyhydroxyꢀ1,4ꢀnaphthoquinones produced by sea urꢀ
chins are of considerable practical interest, since they
exhibit high antioxidant activity1—7 and can be used in
medicine and veterinary for treatment of different human
and animal diseases related to the oxidative stress.
7ꢀEthylꢀ2,3,5,6,8ꢀpentahydroxyꢀ1,4ꢀnaphthoquinone
(echinochrome A), one of the sea urchin pigments, was
used as a basis to develop agents of the Histochrome®
series successfully used in cardiology for treatment of carꢀ
diac ischemia and acute myocardial infarction and in
ophthalmology for treatment of various eye diseases, inꢀ
cluding degenerative processes such as cataract.8
Scheme 1
The most convenient approach to the synthesis of comꢀ
pounds 1 and 2 could have been a double acylation reacꢀ
tion (cycloacylation) of chlorohydroquinone and 2,3ꢀdiꢀ
chlorohydroquinone, respectively, with dichloromaleic
anhydride. The first synthesis of 5,8ꢀdihydroxyꢀ1,4ꢀnaphꢀ
thoquinone (naphthazarin) via cycloacylation of hydroꢀ
quinone with maleic anhydride (Zahn—Ochwat reaction)
was described in the work.9 Since that time, this reaction
became a basic method for the synthesis of functionally
substituted naphthazarins. When maleic,9—14 methylꢀ
maleic (citraconic),10,15 and chloromaleic15—17 anhydrides
are used as acylating agents, the yields of naphthazarins
vary from very low to moderate (~5—45%). The applicaꢀ
tion of more active and more stable under drastic condiꢀ
tions dichloromaleic anhydride sharply increases yields of
functionally substituted naphthazarins. For the first time,
this was shown in the condensation of dichloromaleic
R = H (1, 3, 5), Cl (2), OH (4), OMe (6)
Reagents and conditions: i. MeOH, CsF, Al2O3, 90—95 °C;
ii. 48% aq. HBr, Δ.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 0993—1003, April, 2016.
1066ꢀ5285/16/6504ꢀ0993 © 2016 Springer Science+Business Media, Inc.

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Russ.Chem.Bull., Int.Ed., Vol. 65, No. 4, April, 2016
Novikov et al.
anhydride with 1,2ꢀdihydroxyꢀ3,4ꢀdimethoxybenzene:16,17
the yield of 6,7ꢀdichloroꢀ2,3ꢀdihydroxynaphthazarin was
75%. In the case of cycloacylation of hydroquinone dimeꢀ
thyl ether, the yield of 2,3ꢀdichloronaphthazarin was close
to quantitative (97%).18 The potential of dichloromaleic
anhydride as an acylating agent in the cycloacylation reꢀ
actions of monoꢀ, 2,3ꢀdiꢀ, 2,5ꢀdiꢀ, and 2,3,5ꢀtrisubstitutꢀ
ed hydroquinones is studied for quite a number of subꢀ
strates.16—24 As a rule, the hydroquinones bear alkyl, hyꢀ
droxy, and alkoxy electronꢀdonating groups. Haloꢀsubꢀ
stituted hydroquinones were used in these reactions
much less often. Cycloacylation of 2ꢀchlorohydroquinone
with dichloromaleic anhydride is described in several
works19—21,23,24 and in the patent literature,25—28 whereas
acylation of 2,3ꢀdichlorohydroquinone is considered only
in the work.19 In these works, the authors concentrated
only on the isolation of the target triꢀ and tetrachloronaphꢀ
thazarins, paying virtually no attention to the inꢀdepth
studies of the reaction courses.
only hydroquinone methyl ethers 7 and 8 (Scheme 2). The
reactions were carried out with an excess of anhydride 9
(molar ratio 7 (or 8) : 9 = 1 : 2) in the melt of the mixture
of anhydrous AlCl3 and anhydrous NaCl (molar ratio 2 : 1)
upon heating within the range from 170 to 220 °C. The
reaction time varied from 1.5 to 10 min.
The results of the reaction of 2ꢀchlorohydroquinone
dimethyl ether (7) with anhydride 9 are given in Table 1.
Scheme 2
Results and Discussion
The purpose of the present work is to in detail study the
influence of reaction conditions of cycloacylation of
2ꢀchloroꢀ and 2,3ꢀdichlorohydroquinones with dichloroꢀ
maleic anhydride on the yield of the target compounds, to
establish structures of all the reaction products, and to
clarify mechanisms of their formation.
R = H (7), Cl (8);
R
1 = Cl, R2 = H (1); R1 = R2 = Cl (2); R1 = R2 = H (10)
In the known cycloacylation reactions of hydroquinoꢀ
nes with maleic anhydrides, both the free hydroquinones
and their derivatives (acetates and methyl ethers) were
used. Using the reaction of dichloromaleic anhydride with
unsubstituted hydroquinone as an example, we have shown
that in the case of hydroquinone dimethyl ether the yield
of 2,3ꢀdichloronaphthazarin was 98%, whereas for free
hydroquinone and its diacetate the yield decreased to 72
and 64%, respectively.19 Therefore, in our studies we used
Reagents and conditions: 1) AlCl3, NaCl, Δ; 2) 10% aq. HCl.
The data in Table 1 show that the optimal yields of
trichloronaphthazarin 1 can be obtained by running the
reaction in the temperature range from 175 to 185 °C,
with the heating time from 5 to 10 min. Under these conꢀ
ditions, the highest yield of product 1 was 61%. At higher
temperature (215—220 °C), the yield of 1 did not exceed
48%, which was somewhat higher than in the case when
Table 1. Composition and yields of products of cycloacylation of hydroquinone dimethyl ethers 7 and 8 with dichloromaleic
anhydride 9
Substrate
T/°C
t/min
Product yields (%)*
11
1
2
10
Other products
7
170—175
170—175
180—185
180—185
190—195
215—220
180—185
175—180
175—180
3
7
5
10
5
5
10
1.5
3
43.0
54.0
55.0
61.0
51.0
48.0
42.0
34.0
52.0
0.5
1.0
1.0
1.0
2.0
3.0
2.5
32.0
1.0
6.0
7.0
7.5
9.0
9.5
10.0
2.0
—
—
—
—
—
—
—
1.5
2.5
3.0
4.0
—
—
—
12 (20.0), 13 (10.0), 14 (5.0), 15 (3.0), 16 (1.0)
12 (1.0), 17 (30.0)
7**
8
—
0.5
6.0
17 (38.0), 23 (3)
* Isolated product yields calculated on reacted substrate.
** With additive of anhydrous FeCl3 (molar ratio AlCl3 : NaCl : FeCl3 = 8 : 4 : 1).

Cycloacylation of chlorohydroquinones
Russ.Chem.Bull., Int.Ed., Vol. 65, No. 4, April, 2016
995
free chlorohydroquinone was used as the substrate under
the same conditions (39%).25,26 The moderate yields of
the target product 1 can be explained by the side processes
of the formation of products 2, 10, and 11, which enꢀ
hanced as the temperature increased from 170 to 220 °C.
The attempt to increase the yield of product 1 by the addiꢀ
tion to the reaction mixture of a Lewis acid such as anhyꢀ
drous FeCl3 has proved unsuccessful. The yield of product 1
was only 42% (see Table 1). Apparently, this is partially due
to the fact that in the presence of FeCl3, the melt of AlCl3
and NaCl became very dense, which made it
very difficult to evenly stir the reaction mixꢀ
ture. As a result of this, a fair part of subꢀ
strate 7 was not involved in the condensation
with anhydride 9, rather it was converted to
chlorohydroquinone 12 via the O—Me
bond cleavage upon the action of AlCl3.
It is interesting to establish the mechanisms of the
formation of both the major and the side reaction
products of cycloacylation of substrates 7 and 8 with
anhydride 9.
In the melt, AlCl3 exists as a dimer forming probably
an ion pair.29 At the same time, as it is known, solid anhyꢀ
drous AlCl3 is considerably better conductor of electric
current than the melted salt, that, apparently, can be exꢀ
plained by the transition from an ionic structure to the
molecular one.30,31 It is also known that acyl halides and
anhydrides form complexes with Lewis acids having the
structure of oxocarbenium ion salts.32,33 In the case of
anhydride 9, the reaction with the ion pair of aluminum
trichloride should lead to the formation of the double salt A
(Scheme 3), which can exist in both Zꢀ and Eꢀform.
Earlier, it was suggested that the reaction of the double
salt A with the corresponding hydroquinone (for example,
7) gives the acylation product EꢀB with transꢀconfiguraꢀ
tion of the double bond of the acyl chain, which under the
reaction conditions isomerizes to form the intermediate
ZꢀB.15,34,35 It was believed that this intermediate is stabiꢀ
lized via the formation of a bond between the aluminum
atom of the salt group at position 3´ and the oxygen atom
of the OAlCl2 group at position 1. The second act of acylꢀ
ation of the aromatic ring in the intermediate ZꢀB leads to
the ring closure with the formation of a cyclic product in
the form of complex C, which after decomposition with
an acid gives the target naphthazarin.
The side processes became even more
significant when 2,3ꢀdichlorohydroquinone dimethyl ether
(8) was used as the substrate (see Scheme 2). Running the
reaction at 175—180 °C for 1.5 min gave a mixture of
approximately equal amounts of the target tetrachloroꢀ
naphthazarin 2 and, quite unexpectedly, trichloronaꢀ
phthazarin 1 (see Table 1). An increase in the reaction
time at this temperature to 3 min led to a decrease in the
yield of the target product 2 to 1%, with the yield of prodꢀ
uct 1 increasing to 52%. The separation of the mixture of
reaction products also gave 2,3ꢀdichloronaphthazarin (10)
(6%) and indenonecarboxylic acid (11) (0.5%) (see Table 1).
The structure of all the reaction products was unambiꢀ
guously found based on the IR spectra, 1D and 2D 1H and
13C NMR spectra, as well as mass spectra.
In a model experiment, we tested a possibility of the
formation of the double salt EꢀA in the course of ring
opening in anhydride 9. Heating anhydride 9 in the melt
of anhydrous AlCl3 and NaCl at 180—185 °C for 7 min
Scheme 3

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Novikov et al.
gave only 2,3ꢀdichloromaleic acid. From this it follows
that the formation of the intermediate EꢀB and its further
isomerization to ZꢀB are possible only with participation
of hydrogen chloride liberated in the course of acylation of
substrate 7, whereas the existence of the equilibrium
distance less than 2.3 Å. There are two ways to remove this
group: either through the heterolysis of the C(4´)—OAlCl2
bond in the intermediate ZꢀB, or through its homolysis.
The first of them is given in Scheme 4.
According to the traditional notions about mechanism
of the Friedel—Crafts acylation of arenes,36,37 the reacꢀ
tion of oxocarbenium ion (acylium cation) ZꢀA with the
substrate 7 gives the monoacyl derivative E through the
intermediate formation of σꢀcomplex D (for convenience,
the step of the formation of πꢀcomplex is not shown) (see
Scheme 4). The protonation of the oxygen atom in carbꢀ
oxylate anion of intermediate E should give oxonium catꢀ
ion F, the heterolysis of the C(4´)—O bond in which would
lead to the formation of oxocarbenium ion G. Further
transformation of intermediate G to naphthazarin interꢀ
mediate I should follow a similar pathway as in the formaꢀ
tion of intermediate E in the acylation of substrate 7 with
oxocarbenium ion ZꢀA. To approximately assess the energy
requirements in the sequence of reactions E → F → G →
→ H → I, we carried out quantum chemical calculations
by B3LYP/6ꢀ311G(d) method, using approaches described
in the works.38,39
→
EꢀB
ZꢀB is a result of additionꢀelimination of HCl at
←
the conjugated double bond of intermediate B.
The mechanism of cyclization of 3ꢀbenzoylacrylic acid
salts of type ZꢀB to naphthazarin complexes of type C is
still unclear. This issue is a key moment in the cycloacylaꢀ
tion reactions of hydroquinones with maleic anhydrides.
Computer modeling of spatial structure of intermediꢀ
ate ZꢀB (see Scheme 3) showed that the reaction centers
C(6) and C(4´) cannot be closer than 4 Å apart because of
the strong steric interactions between the OAlCl2 funcꢀ
tional groups at atoms C(1) and C(4´). This cannot happen
even if a MeO group is at position 1 instead of the OAlCl2
group. This circumstance excludes the possibility of ring
closure in the intermediate ZꢀB through, for example, the
attack by the bond C(1)=C(6) on the electrophilic center
C(4´). Only the absence of the OAlCl2 group at position 4´
gives the opportunity for the reaction centers C(6) and
C(4´) in such an intermediate to approach each other to the
The results of these calculations are given in Table 2.
Scheme 4

Cycloacylation of chlorohydroquinones
Russ.Chem.Bull., Int.Ed., Vol. 65, No. 4, April, 2016
997
Table 2. Enthalpy (ΔHr) of reactions (1)—(4)
Table 3. Enthalpy (ΔHr) of reactions (5)—(9)
Reaction
ΔHr/kcal mol–1
Reaction
ΔHr/kcal mol–1
E + HAlCl4 → F + AlCl4– (1)
F → G + HOAlCl2 (2)
G → H (3)
77.8
98.5
–46.8
–145.5
Е → J + Cl2AlO• (5)
J → K (6)
147.6
–43.0
–79.6*
–67.6**
–12.0**
K + Cl2AlO• → I + HOAlCl2 (7)
К + Cl2AlO• → L (8)
L → I + HOAlCl2 (9)
H → I + HAlCl4 (4)
* Direct conversion K → I.
** Indirect conversion K → I.
The reactions (1) and (2) require heating, the reacꢀ
tions (3) and (4) proceed with evolution of heat. A total
enthalpy of the fourꢀstep sequence of reactions E → F →
→ G → H → I is –16.0 kcal mol–1
.
lute values of enthalpies of these processes is equal to
41.0 kcal mol–1. Therefore, both the initial step of acylaꢀ
tion of hydroquinones with dichloromaleic anhydride and
the step of cyclization of forming intermediate with the
structure of βꢀaroylacryl acid salt should follow a classic
mechanism of Friedel—Crafts aromatic electrophilic acylꢀ
ation. Thus, the mechanism of Zahn—Ochwat cycloacylꢀ
ation reaction of hydroquinones with maleic anhydrides
essentially is a double Friedel—Crafts acylation.
The formation of indenonecarboxylic acid 11, one of
the side products of cycloacylation reaction of substrate 7
with anhydride 9, can be regarded as the cyclization of
intermediate EꢀB with transꢀconfiguration of the double
bond in the side chain (see Scheme 3). The conversion of the
latter to product 11, apparently, can proceed via the attack
by the C(1)=C(6) bond on the electrophilic center C(3´)
(the transformation chain EꢀB → L → M → N → 11)
(Scheme 6). In the most favorable conformation of interꢀ
mediate EꢀB, the distance between the reaction centers
C(6) and C(3´) is 2.80 Å, whereas the distance between
A primary act of acylation of substrate 7 with acylium
cation ZꢀA should be directed at paraꢀposition to the chloꢀ
rine atom. As it is known, the Cl atom, simultaneously
exhibiting –Iꢀ and +Mꢀeffects, directs electrophilic subꢀ
stitution at oꢀ and pꢀpositions due to the +Mꢀeffect, howꢀ
ever, no substitution at oꢀposition was observed.
The homolytic mechanism of the C(4´)—OAlCl2 bond
cleavage in intermediate E is represented by Scheme 5.
Electron energies of free radicals were calculated by
the (U)B3LYP/6ꢀ311G(d) method. The calculation reꢀ
sults are given in Table 3.
A total enthalpy of threeꢀstep conversion E → J → K →
→ I is 25.0 kcal mol–1. A total enthalpy of fourꢀstep conꢀ
version E → J → K → L → I has the same value. The
evaluation of total enthalpies of two pathways of cyclizaꢀ
tion of 3ꢀaroylacrylic acid salts of type E to naphthazarin
intermediates of type I allows us to draw a conclusion that
the ionic mechanism of this process is energetically more
favorable than the radical one. The difference in the absoꢀ
Scheme 5

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Novikov et al.
Scheme 6
M: R = H or Me
C(6)—H and C(3´)—Cl is 1.25 Å. The favorable spatial
arrangement of these atoms allows one to suggest that the
cyclization of intermediate EꢀB can also proceed through
the direct attack by the electron density of the C(6)—H
bond on atom C(3´) with the extrusion of the HCl moleꢀ
cule (EꢀB→M).
Both compounds treated with heat in the melt of anꢀ
hydrous AlCl3 and NaCl at 180—185 °C for 10 min showed
1
high stability. In the H NMR spectrum of the product
obtained from substrate 1 after the workꢀup of the reacꢀ
tion mixture, the signals of the trace amounts of tetraꢀ
chloronaphthazarin 2 (0.7%) and 2,3ꢀdichloronaphthazꢀ
arin 10 (0.2%) were found (Scheme 7). The appearance of
compound 2 can be considered as a result of the attack of
an H• atom formed by the homolysis of the bond in the
hydrogen chloride molecule, which is liberated in the
course of the reaction, on atom C(6) of the substrate, the
further addition of radical Cl• at position 7 of the radical
intermediate, and the oxidation of forming dihydro derivꢀ
ative with air oxygen. Compound 10 appeared as a result
of the homolysis of the C(6)—Cl bond in the substrate and
the attack by the H• atom on the radical formed. The data
on the homolysis energies for different bonds in compounds
in question are given in Table 4. The formation of the
trace amounts of compounds 1 and 10 in the case of tetraꢀ
chloronaphthazarin 2 can be explained similarly.
The results of the model experiments described above
clearly show that the formation of considerable amounts
of side products during cycloacylation of substrates 7 and
8 with anhydride 9 are directly related to the processes of
transformation of the substrates to be acylated. In this
connection, we carried out model experiments dealing with
the stability of substrates 7 and 8 under the reaction conꢀ
ditions. Heating the substrate 7 in the melt of anhydrous
AlCl3 and NaCl at 180—185 °C for 7 min led to the transꢀ
formation of 81% of diether 7 to the corresponding chloroꢀ
hydroquinone 12, whereas 19% of substrate 7 underwent
The formation of unequal amounts of tetrachloronaphꢀ
thazarin 2 and 2,3ꢀdichloronaphthazarin 10 in the cycloꢀ
acylation of chlorohydroquinone 7 with anhydride 9 (see
Table 1) allows one to draw a conclusion that this is not
a result of disproportionation of two molecules of trichloroꢀ
naphthazarin 1, which would give their equal amounts,
but some other process. We have already mentioned earliꢀ
er that the cycloacylation of 1,2ꢀdihydroxyꢀ3,4ꢀdimethꢀ
oxybenzene with monochloromaleic anhydride leads to
the formation of a mixture of 6,7ꢀdichloroꢀ2,3ꢀdihydroxyꢀ
naphthazarin, 6ꢀchloroꢀ2,3ꢀdihydroxynaphthazarin, and
2,3ꢀdihydroxynaphthazarin (molar ratio of 1 : 2 : 1, respecꢀ
tively).16,17 The authors suggested that the formation of
such a mixture is a result of disproportionation of two
molecules of the target product of condensation of 6ꢀchloroꢀ
2,3ꢀdihydroxynaphthazarin. The same picture was obꢀ
served in cycloacylation of chlorohydroquinone with maꢀ
leic anhydride, when a mixture of 2,3ꢀdichloronaphthꢀ
azarin 10, monochloronaphthazarin, and naphthazarin
was obtained in the molar ratio of 1 : 2 : 1, respectively.17
If trichloronaphthazarin 1 itself theoretically can unꢀ
dergo disproportionation, tetrachloronaphthazarin 2 should
not give this reaction at all. Nontheless, we tested stabiliꢀ
ties of compounds 1 and 2 under conditions of cycloacylꢀ
ation reaction.

Cycloacylation of chlorohydroquinones
Russ.Chem.Bull., Int.Ed., Vol. 65, No. 4, April, 2016
999
Table 4. Enthalpy of homolytic dissociation (D) of C—H and
C—Cl bonds in compounds 1, 2, 7, and 8 calculated by the
(U)B3LYP/6ꢀ311G(d) method
Scheme 8
Comꢀ
pound
D/kcal mol–1
C(2)—Cl C(3)—H C(5)—H C(6)—H C(6)—Cl C(7)—H
1*
2*
7
—
—
—
113.0
—
—
—
109.6
109.3
—
—
108.9
—
88.1
—
—
109.2
86.1
89.2
87.1
—
—
—
8
—
* In the form of aluminum complexes of type C (see Scheme 3).
Scheme 7
R = Me (7, 8, 18—20), H (12—16)
Reagents and conditions: (i) AlCl3, NaCl, 180—185 °C, 7 min.
Scheme 9
Reagents and conditions: i. Homolysis, DHCl = 95.7 kcal mol–1
ii. AlCl3, NaCl, 180—185 °C, 10 min.
;
disproportionation with the formation of a mixture of hyꢀ
droquinones 13 (50%), 14 (29%), 15 (14%), and 16 (6%)
(Scheme 8).
The calculations data obtained by the (U)B3LYP/6ꢀ
311G(d) method showed that the C(2)—Cl bond of the
substrate should undergo homolysis the easiest, then the
C(6)—H and C(5)—H bonds, and the most difficult the
C(3)—H bond (see Table 4). The enthalpy values of the
homolysis of C—H bonds (DCH) in compound 7 show
that no formation of 2,3ꢀdichlorohydroquinone (16)
should take place, however, the actual ratio of obtained
dichlorohydroquinones 14, 15, and 16 does not correꢀ
spond to that predicted based on the DCH value.
R = Me (7, 8, 21, 22), H (12, 16, 17, 23)
Reagents and conditions: i. AlCl3, NaCl, 180—185 °C, 1.5 min;
ii. AlCl3, NaCl, 180—185 °C, 3 min.

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Novikov et al.
Apparently, the ratio of products of disproportionation
of substrate 7 observed in the experiment is a result of the
strong influence of high reaction temperature on the
homolytic substitution of hydrogen atoms in substrate 7 upon
the action of radicals Cl•. At increased temperature, the
attack of these radicals becomes less selective and its effiꢀ
ciency depends less on the relative differences in the elecꢀ
tron density in oꢀ, mꢀ, and pꢀpositions of compound 7.
Substrate 8 has proved to be more inclined to disproꢀ
portionation. Its heating in the melt of anhydrous AlCl3
and NaCl at 180—185 °C for 1.5 min led to the transforꢀ
mation of 35% of diether 8 to the corresponding 2,3ꢀdiꢀ
chlorohydroquinone (16), whereas 65% of substrate 8 underꢀ
went disproportionation with the formation of a mixture
of hydroquinones 12 (49%) and 17 (50%) (Scheme 9).
An increase in the reaction time to 3 min led to the
formation of only trace amounts of 2,3ꢀdichlorohydroꢀ
quinone (16). The substrate 8 was practically entirely conꢀ
verted to the mixture of chlorohydroquinone (12) (42%),
trichlorohydroquinone (17) (40%), and a small amounts
of tetrachlorohydroquinone (23) (6%) and hydroquinone
(13) (5%). The formation of hydroquinones 12 and 17 is
a result of disproportionation of two molecules of 2,3ꢀdiꢀ
chlorohydroquinone (16), whereas hydroquinones 13 and
23 are formed by a weakly pronounced radical substitution
of a hydrogen atom at position 6 of compound 17 by the
chlorine atom of compound 12.
Later, the whole set of hydroquinones 12—16 was
found among the products of acylation of substrate 7 with
anhydride 9 in the presence of FeCl3. From this fact it
follows that when the cycloacylation process of the subꢀ
strate is hindered for some reasons, the radical reactions
of disproportionation of haloꢀsubstituted hydroquinones
begin to actively take place.
The results of these model experiments allow us to
explain why considerable amounts of tetrachloronaphthꢀ
azarin 2 and 2,3ꢀdichloronaphthazarin 10 are formed in
the course of cycloacylation of substrate 7. The first is the
product of acylation of substrate 8 (or 16) present in the
reaction mixture, whereas the second is obtained from
substrate 18 (or 13). Similarly, the appearance among the
products of acylation of substrate 8 such compounds as
trichloronaphthazarin 1 and 2,3ꢀdichloronaphthazarin 10
is due to the presence of substrates 7 (or 12) and 18 (or 13)
in the reaction mixture.
such as hydroquinones 12, 13, and 16, a radical substituꢀ
tion of a chlorine atom of compound 2 with the hydrogen
atom take place with the formation of compound 1. Comꢀ
pound 2 has the lowest enthalpy of the homolytic dissoꢀ
ciation of the C—Cl bond among all the compounds unꢀ
der study (see Table 4).
It should be noted that out of hydroquinones 14, 15,
and 17 formed in the radical disproportionation processes
of substrates 7 and 8 during acylation with anhydride 9,
only monoꢀCꢀacyl derivatives are formed, which do not
undergo further conversion to the corresponding naphthꢀ
azarins, whereas hydroquinone 23 does not give the
Cꢀacylation reaction at all.
The facts listed above allow us to draw a conclusion
that the reason for the formation of mixtures of products
during cycloacylation of monoꢀ and 2,3ꢀdichloroꢀsubstiꢀ
tuted hydroquinones with dichloromaleic anhydride unꢀ
der drastic conditions is the tendency of substrates to disꢀ
proportionation. As a result, instead of one starting hydroꢀ
quinone the reaction mixture contains two or three hydroꢀ
quinones, from which the mixtures of products 1, 2, and
10 are formed. It was found that under certain conditions
of cycloacylation reaction, tetrachloronaphthazarin 2 can
be converted to trichloronaphthazarin 1 as a result of
radical substitution of a chlorine atom with the hydrogen
atom. The formation of side products decreases in differꢀ
ent degree the yields of the target triꢀ and tetrachloroꢀ
naphthazarins.
The results of our studies allow us to explain the forꢀ
mation of a mixture of products in the cycloacylation of
chlorohydroquinone with maleic anhydride.17 The disproꢀ
portionation of the substrate gives a mixture of 2,3ꢀdichloꢀ
rohydroquinone and hydroquinone, whose acylation with
the anhydride gives a mixture of naphthazarin and 2,3ꢀdiꢀ
chloronaphthazarin, together with the target 2ꢀchloroꢀ
naphthazarin.
The situation is more complex in the case of cycloacylꢀ
ation of 1,2ꢀdihydroxyꢀ3,4ꢀdimethoxybenzene with monoꢀ
chloromaleic anhydride.16,17. If trichloronaphthazarin 1,
as it was mentioned above, does not undergo disproporꢀ
tionation under the cycloacylation reaction conditions,
why the target product of this reaction, i.e., 6ꢀchloroꢀ2,3ꢀ
dihydroxynaphthazarin should undergo it? It is possible
that the formation of a mixture of 6,7ꢀdichloroꢀ2,3ꢀdihydrꢀ
oxynaphthazarin, 2,3ꢀdihydroxynaphthazarin, and the
target product (molar ratio 1 : 1 : 2) observed in this case is
a result of disproportionation of monochloromaleic anꢀ
hydride to dichloromaleic and maleic anhydrides, which,
acylating the substrate, give the mixture of the indicated
products. However, this suggestion requires experimental
confirmation.
In the case of substrate 8, the reaction time has a strong
influence on the composition of the products formed. If
after 1.5 min, a mixture of approximately equal amounts
(molar ratio) of compounds 1 and 2 is formed, then after
3 min compound 1 becomes a predominant product, whereas
compound 2 virtually completely disappears. We already
mentioned above that in the model experiment, tetraꢀ
chloronaphthazarin 2 showed high stability under the
cycloacylation reaction conditions. In the case in quesꢀ
tion, its absence in the reaction mixture can be explained
by the fact that in the presence of hydrogen atom donors
The results of the present study allow us to state that
the first step of cycloacylation of chlorohydroquinones
with dichloromaleic anhydride proceeds as electrophilic
substitution of a proton in the aromatic ring of the subꢀ
strate with the oxocarbenium ion (acylium cation) formed

Cycloacylation of chlorohydroquinones
Russ.Chem.Bull., Int.Ed., Vol. 65, No. 4, April, 2016
1001
The elution with the mixture of hexane—acetone (8 : 1) gave
2,6ꢀdichlorohydroquinone (15) (0.048 g, 14%), colorless crystals,
m.p. 163—165 °C (Ref. 42: 164 °C). IR (CDCl3), ν/cm–1: 3601,
3549, 2925, 2861, 1499, 1450, 1336, 1304, 1270, 1237, 1194,
by the anhydride ring opening upon the action of alumiꢀ
num trichloride, i.e. as a traditional Friedel—Crafts acylꢀ
ation of arenes. The second step of cycloacylation related
to the ring closure in the formed cisꢀ3ꢀ[4ꢀchloro(3,4ꢀdiꢀ
chloro)ꢀ2,5ꢀdihydroxy]benzoylꢀ2,3ꢀdichloroacrylic acid
salt proceeds according to the results of theoretical calcuꢀ
lations, also following the mechanism of electrophilic acylꢀ
ation of arenes.
1
1175, 1039. H NMR (CDCl3), δ: 5.35 (br.s, 1 H, C(1) OH);
5.45 (br.s, 1 H, C(4) OH); 6.81 (s, 2 H, H(3), H(5)). 13C NMR
(CDCl3), δ: 115.6 (C(3), C(5)); 121.9 (C(2), C(6)); 142.8 (C(1));
148.8 (C(4)). 1H NMR (DMSOꢀd6), δ: 6.75 (s, 2 H, H(3), H(5));
9.24 (br.s, 1 H, C(1) OH); 9.57 (br.s, 1 H, C(4) OH). 13C NMR
(DMSOꢀd6), δ: 115.4 (C(3), C(5)); 123.2 (C(2), C(6)); 141.7
(C(1)); 150.8 (C(4)).
Experimental
The elution with the mixture of hexane—acetone (7 : 1) gave
2,3ꢀdichlorohydroquinone (16) (0.019 g, 6%), colorless crystals,
1
Melting points were determined on a Boetius heating stage
and were not corrected. IR spectra were recorded on a Bruker
Equinox 55 spectrophotometer in solutions in CDCl3 or in KBr
m.p. 142—144 °C (Ref. 43: 144 °C). H NMR (DMSOꢀd6), δ:
6.76 (s, 2 H, H(5), H(6)); 9.25 (s, 2 H, 2 OH). 13C NMR
(DMSOꢀd6), δ: 115.3 (C(5), C(6)); 119.0 (C(2), C(3)); 147.3
(C(1), C(4)).
1
pellets. H and 13C NMR spectra were recorded on a Bruker
AVANCE DPXꢀ300 spectrometer (1H, 300.13 MHz; 13C,
75.47 MHz) in solutions in CDCl3 or DMSOꢀd6. Internal stanꢀ
dard Me4Si. To unambiguously assign signals of 1H and 13C
The elution with the mixture of hexane—acetone (5 : 1) gave
2ꢀchlorohydroquinone (12) (1.17 g, 81%), colorless crystals,
m.p. 101—102 °C, identical to commercial product (Alfa Aesar).
1H NMR (DMSOꢀd6), δ: 6.56 (dd, 1 H, H(5), J = 9.1 Hz,
J = 2.8 Hz); 6.71 (d, 1 H, H(3), J = 2.8 Hz); 6.77 (d, 1 H, H(6),
J = 9.1 Hz); 9.01 (br.s, 1 H, C(1) OH); 9.21 (br.s, 1 H, C(4)
OH). 13C NMR (DMSOꢀd6), δ: 114.8 (C(5)); 116.1 (C(6)); 117.3
(C(3)); 119.6 (C(2)); 145.6 (C(1)); 150.3 (C(4)).
1
nuclei, different procedures of 1D and 2D H and 13C NMR
spectroscopy were used (DEPTꢀ135, COSYꢀ45, HSQC, and
HMBC). Mass spectra (EI, 70 eV) were obtained on an AMD
604 S instrument (8 kW) with direct injection of the samples.
Elemental analysis was performed on a Flash EA1112 C,H,Nꢀ
analyzer. Reaction progress and individuality of obtained comꢀ
pounds were monitored by TLC on Silufol UV 254 plates in
the systems benzene—hexane (4 : 1) and hexane—acetone
(2 : 1)—(1 : 1). Individual compounds were isolated from mixꢀ
tures of reaction products by column chromatography on the
columns with SiO2 (Alfa Aesar, 70—230 μm), eluting with mixꢀ
tures of hexane or benzene with acetone. The yields of comꢀ
pounds were not optimized. Compounds 7 and 9 were commerꢀ
cially available (Lancaster, Aldrich). Compound 8 was obtained
by methylation of 2,3ꢀdichlorohydroquinone 16 synthesized from
hydroquinone 13 according to the known procedure.40 Industrial
dichloromaleic anhydride 9 before use was mixed with an equal
(w/w) amount of P2O5 and sublimed at atmospheric pressure at
the temperature close to the melting point of the anhydride.
Anhydrous powdered AlCl3 and anhydrous NaCl were used in
the work. Quantum chemical calculations were performed using
the GAUSSIAN 03 software package.41
Disproportionation of 2ꢀchloroꢀ1,4ꢀdimethoxyhydroquinone
(7) under cycloacylation reaction conditions. Substrate 7 (1.73 g,
10.0 mmol) was added to the melt of anhydrous AlCl3 (8.54 g,
64.0 mmol) and NaCl (1.87 g, 32.0 mmol) with vigorous stirring
at 150 °C, the temperature of the mixture was increased to
180—185 °C and maintained for 7 min. Then, the mixture was
cooled to room temperature, and diluted with 10% aqueous HCl
(60 mL) and distilled water (60 mL). The reaction products were
extracted with AcOEt (5×20 mL), the combined extracts were
washed with saturated aqueous NaCl (3×15 mL) and dried with
Na2SO4, the solvent was evaporated at reduced pressure, the
residue was subjected to chromatography on a column with SiO2.
The elution with the mixture of hexane—acetone (9 : 1) gave
2,5ꢀdichlorohydroquinone (14) (0.096 g, 29%), colorless crystals,
m.p. 168—170 °C, identical to commercial product (Alfa Aesar).
1H NMR (CDCl3), δ: 5.57 (br.s, 2 H, 2 OH); 7.03 (s, 2 H, H(3),
H(6)). 13C NMR (CDCl3), δ: 115.0 (C(3), C(6)); 119.9 (C(2),
C(5)); 145.7 (C(1), C(4)). 1H NMR (DMSOꢀd6), δ: 6.92 (s, 2 H,
H(3), H(6)); 9.75 (s, 2 H, 2 OH). 13C NMR (DMSOꢀd6), δ: 117.0
(C(3), C(6)); 118.3 (C(2), C(5)); 145.9 (C(1), C(4)).
The elution with the mixture of hexane—acetone (4 : 1) gave
hydroquinone (13) (0.105 g, 50%), colorless crystals, m.p.
170—172 °C, identical to commercial product (Alfa Aesar).
1H NMR (CDCl3), δ: 4.45 (br.s, 2 H, 2 OH); 6.72 (s, 4 H, H(2),
H(3), H(5), H(6)). 13C NMR (CDCl3), δ: 116.1 (C(2), C(3),
1
C(5), C(6)); 149.4 (C(1), C(4)). H NMR (DMSOꢀd6), δ: 6.56
(s, 4 H, H(2), H(3), H(5), H(6)); 8.56 (s, 2 H, 2 OH). 13C NMR
(DMSOꢀd6), δ: 115.7 (C(2), C(3), C(5), C(6)); 149.8 (C(1), C(4)).
Disproportionation of 2,3ꢀdichloroꢀ1,4ꢀdimethoxyhydroquinone
(8) under cycloacylation reaction conditions. Substrate 8 (2.07 g,
10.0 mmol) was added to the melt of anhydrous AlCl3 (8.54 g,
64.0 mmol) and NaCl (1.87 g, 32.0 mmol) with vigorous stirring
at 150 °C, the temperature of the mixture was increased to
180—185 °C and maintained for 1.5 min. The treatment similar
to that described above for substrate 7 gave a mixture of products,
which was subjected to chromatography on a column with SiO2.
The elution with the mixture of hexane—acetone (10 : 1)
gave 2,3,5ꢀtrichlorohydroquinone (17) (0.69 g, 50%), colorless
crystals, m.p. 134—136 °C (Ref. 44: 136 °C). 1H NMR (DMSOꢀd6),
δ; 7.09 (s, 1 H, H(6)); 9.65 (br.s, 1 H, C(1) OH); 9.80 (br.s, 1 H,
C(4) OH). 13C NMR (DMSOꢀd6), δ: 115.5 (C(6)); 118.4 (C(2));
120.2 (C(5)); 121.3 (C(3)); 145.2 (C(4)); 146.8 (C(1)).
The elution with the mixture of hexane—acetone (7 : 1) gave
compound 16 (0.63 g, 35%), the elution with the mixture of
hexane—acetone (5 : 1) gave compound 12 (0.46 g, 49%) identiꢀ
cal to the sample described above.
Cycloacylation of 2ꢀchlorohydroquinone dimethyl ether (7).
A mixture of substrate 7 (1.38 g, 8.0 mmol) and anhydride 9
(2.67 g, 16.0 mmol) was added to the melt of anhydrous AlCl3
(8.54 g, 64.0 mmol) and NaCl (1.87 g, 32.0 mmol) with vigorous
stirring at 150 °C, the temperature of the mixture was increased
to the values given in Table 1 and maintained for the indicated
time. Then, the reaction mixture was cooled to room temperaꢀ
ture, diluted with 10% aqueous HCl (50 mL), and was allowed to
stand for 12 h. The product formed was separated, washed with
hot (55—60 °C) water (10×40 mL), dried to the constant weight,
and subjected to chromatography on a column with SiO2.

1002
Russ.Chem.Bull., Int.Ed., Vol. 65, No. 4, April, 2016
Novikov et al.
The elution with the mixture of hexane—benzene (10 : 1)
gave 2,3,6,7ꢀtetrachloroꢀ5,8ꢀdihydroxyꢀ1,4ꢀnaphthoquinone (2)
(0.013—0.079 g, 0.5—3%), Rf 0.65 (benzene—hexane (4 : 1)), red
(10×40 mL), dried to the constant weight, and subjected to chroꢀ
matography on a column with SiO2.
The elution with the mixture of hexane—benzene (10 : 1)
gave compound 2 (0.066 g, 2.5%), the elution with the mixture
of hexane—benzene (4 : 1) gave compound 1 (0.99 g, 42%), the
elution with benzene gave compound 10 (0.045 g, 2%) identical
to the sample described above.
needles, m.p. 256—258 °C (Ref. 45: 258 °C). IR (CDCl3), ν/cm–1
:
3400—2250 (αꢀOH), 1627 (C=O, C=C), 1568 (C=C), 1405.
1H NMR (CDCl3), δ: 12.88 (s, 2 H, 2 αꢀOH). 13C NMR (CDCl3),
δ: 109.2 (C(4a), C(8a)); 139.1 (C(2), C(3), C(6), C(7)); 167.2
(C(1), C(4), C(5), C(8)). MS, m/z (Irel (%)): 327/329/331/333/
335 [M + 1]+ (58), 326/328/330/332/334 [M]+ (100), 292/294/
296/298 [M – Cl + 1]+ (20), 291/293/295/297 [M – Cl]+ (61),
257/259//261 [M – 2Cl + 1]+ (5), 256/258//260 [M – 2Cl]+ (17).
The elution with the mixture of hexane—benzene (4 : 1) gave
2,3,6ꢀtrichloroꢀ5,8ꢀdihydroxyꢀ1,4ꢀnaphthoquinone (1) (1.01—1.43 g,
43—61%), Rf 0.48 (benzene—hexane (4 : 1)), red needles,
The combined acidic mother liquor and washing water (460 mL)
were extracted with AcOEt (6×50 mL), the combined extracts
were washed with saturated aqueous NaCl (3×50 mL), and dried
with Na2SO4. The solvent was evaporated at reduced pressure, the
residue was subjected to chromatography on a column with SiO2.
The elution with the mixture of hexane—acetone (9 : 1) gave
compound 14 (0.057 g, 5%), the elution with the mixture of
hexane—acetone (8 : 1) gave compound 15 (0.034 g, 3%), the
elution with the mixture of hexane—acetone (7 : 1) gave comꢀ
pound 16 (0.011 g, 1%), the elution with the mixture of hexꢀ
ane—acetone (5 : 1) gave compound 12 (0.232 g, 20%), and the
elution with the mixture of hexane—acetone (4 : 1) gave comꢀ
pound 13 (0.07 g, 10%) identical to the sample described above.
Cycloacylation of 2,3ꢀdichlorohydroquinone dimethyl ether
(8). A mixture of substrate 8 (2.07 g, 10.0 mmol) and anhydride 9
(3.34 g, 20.0 mmol) was added to the melt of anhydrous AlCl3
(8.54 g, 64.0 mmol) and NaCl (8.54 g, 64.0 mmol) with vigorous
stirring at 150 °C, the temperature of the mixture was increased
to 175—180 °C and maintained for 1.5 min. The workꢀup similar
to that described above for cycloacylation of substrate 7 gave
a mixture of products, which was subjected to chromatography
on a column with SiO2.
m.p. 174—176 °C (Ref. 24: 174—176 °C). IR (CDCl3), ν/cm–1
:
3350—2200 (αꢀOH), 1628 (C=O, C=C), 1566 (C=C), 1493,
1
1401. H NMR (CDCl3), δ: 7.45 (s, 1 H, H(7)); 12.31 (s, 1 H,
C(8) OH); 12.74 (s, 1 H, C(5) OH). 13C NMR (CDCl3), δ: 109.6
(C(8a)); 110.8 (C(4a)); 130.6 (C(7)); 137.5 (C(6)); 141.5 (C(3));
142.5 (C(2)); 159.6 (C(5)); 162.8 (C(8)); 174.4 (C(1)); 175.2
(C(4)). MS, m/z (Irel (%)): 293/295/297/299 [M + 1]+ (13), 292/
294/296/298 [M]+ (100), 258/260/262 [M – Cl + 1]+ (11), 257/
259/261 [M – Cl]+ (14), 223/225 [M – 2Cl + 1]+ (15), 222/224
[M – 2Cl]+ (18).
The elution with benzene gave 2,3ꢀdichloroꢀ5,8ꢀdihydroxyꢀ
1,4ꢀnaphthoquinone (10) (0.124—0.207 g, 6—10%), Rf 0.30
(benzene—hexane (4 : 1)), red needles, m.p. 194—196 °C (from
1,4ꢀdioxane) (Ref. 10: 192 °C, Ref. 18: 198—199 °C). IR
(CDCl3), ν/cm–1: 3400—2250 (αꢀOH), 1625 (C=O, C=C), 1571
1
(C=C), 1403. H NMR (CDCl3), δ: 7.33 (s, 2 H, H(6), H(7));
The elution with the mixture of hexane—benzene (10 : 1)
gave compound 2 (1.05 g, 32%), the elution with the mixture of
hexane—benzene (4 : 1) gave compound 1 (0.34 g, 34%) identiꢀ
cal to the sample described above.
12.34 (s, 2 H, 2 αꢀOH). 13C NMR (CDCl3), δ: 110.4 (C(4a),
C(8a)); 131.1 (C(6), (C(7)); 142.9 (C(2), (C(3)); 161.1 (C(5),
(C(8)); 177.2 (C(1), (C(4)). MS, m/z (Irel (%)): 259/261/263
[M + 1]+ (59), 258/260/262 [M]+ (100), 257/259/261 [M – 1]+
(45), 224/226 [M – Cl + 1]+ (19), 223/225 [M – Cl]+ (22), 222/
224 [M – Cl – 1]+ (17).
The combined acidic mother liquor and washing water (460 mL)
were extracted according to procedure described above for cycloꢀ
acylation of substrate 7 in the presence of FeCl3 to isolate
a mixture of products, which was subjected to chromatography
on a column with SiO2. The elution with the mixture of hexꢀ
ane—acetone (10 : 1) gave hydroquinone 17 (0.238 g, 34%), the
elution with the mixture of hexane—acetone (5 : 1) gave hydroꢀ
quinone 12 (0.01 g, 1%) identical to the sample described above.
The same amount of the reagents heated at 175—180 °C for
the longer time of 3 min led to the formation of a mixture of
products, which was subjected to chromatography on a column with
SiO2. The elution with the mixture of hexane—benzene (10 : 1)
gave compound 2 (0.033 g, 1%), the elution with the mixture of
hexane—benzene (4 : 1) gave compound 1 (1.51 g, 52%), the
elution with benzene gave compound 10 (0.152 g, 6%), and the
elution with the mixture of benzene—acetone 1 : 1 gave comꢀ
pound 11 (0.014 g, 0.5%) identical to the sample described above.
The elution with the mixture of benzene—acetone (1 : 1)
gave 2,5ꢀdichloroꢀ4,7ꢀdihydroxyꢀ3ꢀhydroxycarbonylindenꢀ1ꢀone
(11) (0.024—0.065 g, 1.5—4%), Rf 0.50 (hexane—acetone (1 : 1))
reddish yellow needles, m.p. >350 °C. IR (KBr), ν/cm–1: 3377
(OH), 3214 (OH), 3280—2150 (COOH), 2923, 2853, 2361, 1698
(C=O), 1681 (C=O), 1619 (C=C), 1572, 1438, 1385, 1302, 1288,
1
1240, 1181, 1163, 1143, 1047, 1032, 881, 777, 743. H NMR
(DMSOꢀd6), δ: 6.02 (br.s, 1 H, C(4) OH); 6.95 (s, 1 H, H(6));
10.77 (br.s, 1 H, C(3) COOH); 16.00 (s, 1 H, C(7) OH). 13C NMR
(DMSOꢀd6), δ: 111.3 (C(7a)); 122.7 (C(6)); 123.8 (C(3a)); 131.8
(C(2)); 134.1 (C(5)); 142.8 (C(3)); 143.0 (C(4)); 151.0 (C(7));
166.9 (COOH); 185.3 (C(1)). MS (EI, 15 eV), m/z (Irel (%)):
275/277/279 [M + 1]+ (31), 274/276/278 [M]+ (100), 273/275/
277 [M – 1]+ (26). Found (%): C, 43.76; H, 1.50; Cl, 25.53.
C10H4Cl2O5. Calculated (%): C, 43.67; H, 1.47; Cl, 25.78.
Cycloacylation of 2ꢀchlorohydroquinone dimethyl ether (7) in
the presence of FeCl3. A mixture of substrate 7 (1.38 g, 8.0 mmol)
and anhydride 9 (2.67 g, 16.0 mmol) was added to the melt of
anhydrous AlCl3 (8.54 g, 64.0 mmol), NaCl (1.87 g, 32.0 mmol).
and anhydrous FeCl3 (1.30 g, 8.0 mmol) with vigorous stirring
at 150 °C, the temperature of the mixture was increased to
180—185 °C and maintained for 10 min. Then, the reaction
mixture was cooled to room temperature, treated with 10% aqueꢀ
ous HCl (60 mL), and allowed to stand for 12 h. The product
formed was separated, washed with hot (55—60 °C) water
This work was financially supported by the Russian
Academy of Sciences (Grant FEB of RAS No. 15ꢀ1ꢀ
5ꢀ0321).
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Received July 20, 2015;
in revised form February 10, 2016