Convenient synthesis of 5-benzyl-2,3,5-trichloro-4,4-dimethoxycyclopent-2- en-1-one and some its reactions

Article abstract of DOI:10.1007/s11178-008-3001-8

5-Benzyl-2,3,5-trichloro-4,4-dimethoxycyclopent-2-en-1-one was synthesized by reaction of 1,2,3,4-tetrachloro-5,5-dimethoxycyclopentadiene with benzyl alcohol in methylene chloride in the presence of powdered sodium hydroxide and benzyltrimethylammonium c

Full text of DOI:10.1007/s11178-008-3001-8

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 3, pp. 321–324. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © F.A. Gimalova, V.A. Egorov, E.G. Galkin, M.S. Miftakhov, 2008, published in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 3,
pp. 329–332.
Convenient Synthesis of 5-Benzyl-2,3,5-trichloro-4,4-dimethoxy-
cyclopent-2-en-1-one and Some Its Reactions
F. A. Gimalova, V. A. Egorov, E. G. Galkin, and M. S. Miftakhov
Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences,
pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia
e-mail: bioreg@anrb.ru
Received March 30, 2007
Abstract—5-Benzyl-2,3,5-trichloro-4,4-dimethoxycyclopent-2-en-1-one was synthesized by reaction
of 1,2,3,4-tetrachloro-5,5-dimethoxycyclopentadiene with benzyl alcohol in methylene chloride in the presence
of powdered sodium hydroxide and benzyltrimethylammonium chloride as phase-transfer catalyst. Deprotec-
tion of the title compound gave 2-benzyl-2,4,5-trichlorocyclopent-4-ene-1,3-dione which was subjected to
unusual intramolecular carbocyclization initiated by molecular iodine.
DOI: 10.1134/S1070428008030019
We recently [1] described convenient procedures
for the transformations of hexachlorocyclopentadiene
into practically important trichlorocyclopentenones I
containing various substituents on C5. In continuation
of our studies on the synthetic potential of intramolec-
ular carbocyclizations of trichlorocyclopentenones
[2, 3], in the present work we focused on 5-benzyl
derivative II. We anticipated that the presence in its
molecule of two oxygen-containing centers and benzyl
substituent will ensure generation and subsequent
closure of oxycarbenium intermediates with formation
of linearly fused tricyclic systems such as compound
III (Scheme 1).
the synthesis of a required amount of compound II. It
involved the use of anhydrous dimethyl sulfoxide and
preparation of sodium phenylmethanolate. We have
found that benzyl derivative II can be successfully
synthesized in a simpler way, under standard condi-
tions of phase-transfer catalysis using KOH or NaOH,
benzyl alcohol, and phase-transfer catalyst (Scheme 2).
The yields of compound II thus obtained were com-
parable with those reported in [4], but the use of tetra-
hydrofuran or methylene chloride as solvent instead of
difficultly removable DMSO considerably simplified
the isolation procedure.
Scheme 2.
Scheme 1.
MeO
OMe
O
Cl
Cl
Cl
Cl
R
Cl
Cl
OMe
OMe
Cl
O
PhCH2OH, 50% NaOH
BTMAC, THF
I
Cl
Cl
O
O
Cl
Cl
OMe
OMe
Cl
Cl
Cl
II, 40–50%
OMe
OMe
OMe
Cl
Cl
Having developed a convenient procedure for the
preparation of ketone II we proceeded with studying
possible ways of its carbocyclization. To generate
carbenium ion at the acetal moiety of II we tried con-
II
III
The procedure proposed previously [4] turned out
to be inconvenient from the preparative viewpoint for
321

GIMALOVA et al.
322
Scheme 3.
O
O
Cl
Cl
Cl
Cl
90% H2SO4 or TiCl4/PhMe
II
–Me+
Cl
O
Cl
O
Me
A
IV, 78%
Scheme 4.
O
Cl
O
O
Cl
Cl
(1) I2, MeCN, Na2CO3
(2) Aqueous HCl
Cl
Cl
CH2N2
Cl
V
IV
+
Cl
Cl
MeO
O
HO
O
VII
V
VI
centrated sulfuric acid and titanium(IV) chloride.
However, in no case the expected primary carbocation
A was transformed into tricyclic compound III.
Instead, loss of methyl cation led to the formation of
cyclopentenedione derivative IV (Scheme 3). We suc-
ceeded in effecting the desired intramolecular cycliza-
tion with compound IV. For this purpose, it was treated
with molecular iodine in acetonitrile. The reaction was
slow, and it afforded 67% of enol V (67%) together
with a minor amount of tricyclic compound VI. The
structure of enol V was confirmed via methylation
with diazomethane, which gave methoxy diketone VII
in almost quantitative yield (Scheme 4).
have found no published analogies of intramolecular
cyclization like IV→VI. We believe that the following
mechanism is possible. The reaction of compound IV
with I2 gives rise to iodoxycarbenium ion B which is
more stable than carbocation A (no elimination of I+
occurs). Cation B undergoes intramolecular cyclization
to produce tertiary hypoiodite C, and homolytic dis-
sociation of the O–I bond gives alkoxy radical D.
Fragmentation of the latter (presumably through inter-
mediate E), followed by retro-aldolization–cyclization,
yields tertiary alcohol F which is converted into
tertiary chloride VI upon treatment of the reaction
mixture with hydrochloric acid (Scheme 5).
The mechanisms of formation of compounds V and
VI are not clear. Hydroxy ketone V could be formed as
a result of alkaline hydrolysis of IV at the C3–Cl bond
due to the presence of traces of moisture in the reaction
mixture, though this version is strongly doubtful. As
concerns the formation of tricyclic product VI, we
While searching for other versions of intramolec-
ular cyclization, ketone II was reduced to secondary
alcohol VIII with sodium tetrahydridoborate, and alco-
hol VIII was brought into the Ritter reaction [5] with
a view to generate iminocarbenium ion G. We believed
that the latter is capable of being converted into the
Scheme 5.
O
Cl
O
O
Cl
Cl
Cl
Cl
IV
Cl
O
O·· ·Iδ+
HO
O
I
I–
Cl
HO
I
Iδ–
B
C
Cl
Cl
O
O
Cl
Cl
O
Aq. HCl
Cl
Cl
VI
Cl
·
O
OH
Cl
Cl
O
D
E
F
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 3 2008

CONVENIENT SYNTHESIS OF 5-BENZYL-2,3,5-TRICHLORO-4,4-DIMETHOXY-...
323
Scheme 6.
OH
O
Cl
Cl
Cl
Cl
NaBH4, EtOH, 0°C
H2SO4, MeCN
II
OMe
Cl
Cl
OH
IX
OMe
VIII
Me
Amide
N
a
Cl
VIII
Cl
a
Heterocycle
Cl
O
G
corresponding amide or undergoing heterocyclization
(Scheme 6). However, no expected transformation
products of cation G were detected. The only product
of the Ritter reaction was hydroxy ketone IX. Pre-
sumably, secondary carbocation G is not generated
from alcohol VIII under these conditions.
ν, cm–1: 511, 678, 835, 1201, 1270, 1234, 1568, 1724,
1
1741. H NMR spectrum, δ, ppm: 3.54 s (2H, CH2),
13
6.97 m (2H) and 7.22 m (3H, C6H5). C NMR spec-
trum, δC, ppm: 41.81 (CH2); 62.94 (C2); 128.45, 129.08,
129.86, 131.63 (Carom); 150.96 (C5, C4); 186.74 (C1, C3).
b. Compound II, 0.14 g (0.42 mmol), was dissolved
in 10 ml of toluene, 0.28 g (1.45 mmol) of TiCl4 was
added, and the mixture was heated under reflux until
the initial compound disappeared (~4–5 h, TLC). The
mixture was then poured into ice water, the organic
layer was separated, and the aqueous phase was ex-
tracted with chloroform (3×10 ml). The extracts were
combined with the organic phase, washed with a solu-
tion of NaHCO3 and a saturated solution of NaCl,
dried over MgSO4, and evaporated, and the residue was
purified by recrystallization. Yield 0.06 mg (~50%).
EXPERIMENTAL
The IR spectra were recorded on UR-20 and
Specord M-80 spectrometers from samples prepared as
1
thin films or dispersed in mineral oil. The H and
13C NMR spectra were measured on a Bruker AM-300
instrument at 300 and 75.47 MHz, respectively, using
CDCl3 as solvent and TMS as internal reference. The
mass spectra (electron impact, 70 eV) were obtained
on a Thermo Finnigan MAT 95XP spectrometer (ion
source temperature 200°C, sample injection tempera-
ture 5–270°C, temperature ramp 22 deg/min). Thin-
layer chromatography was performed using Silufol and
Sorbfil plates; spots were detected by calcination or
spraying with an alkaline solution of potassium per-
manganate.
Reaction of compound IV with iodine. Com-
pound IV, 0.38 g (1.31 mmol), was dissolved in 10 ml
of acetonitrile, 1.4 g (13.1 mmol) of anhydrous
Na2CO3 and 1.66 g (6.53 mmol) of I2 were added, and
the mixture was stirred for ~2 h (until the initial com-
pound disappeared according to the TLC data). The
solvent was evaporated, the residue was treated with
hydrochloric acid to pH 7 and extracted with chloro-
form (3×5 ml), and the extracts were combined,
washed in succession with a solution of Na2S2O3
(5 ml) and a saturated solution of NaCl (2×5 ml), dried
over MgSO4, and evaporated. The residue was sub-
jected to column chromatography on silica gel using
ethyl acetate–petroleum ether (1:20) as eluent to
isolate 0.06 g (~15%) of compound VI. The aqueous
phase was acidified to pH 3 with 30% hydrochloric
acid and extracted with chloroform (4×5 ml), the ex-
tract was dried over MgSO4, and evaporated, and the
2-Benzyl-2,4,5-trichlorocyclopent-4-ene-1,3-di-
one (IV). a. Compound II, 0.2 g (0.66 mmol), was
added to 5 ml of concentrated sulfuric acid cooled to
0°C, and the mixture was stirred for 2 h at 0°C and for
3–4 h at room temperature and extracted with chloro-
form (4×5 ml). The extracts were combined, washed
with a solution of sodium chloride and a 5% solution
of sodium hydrogen carbonate, dried over MgSO4, and
evaporated. The residue was recrystallized from ethyl
acetate–petroleum ether (1:10). Yield 0.14 g (78%),
colorless crystals, sublimes above 100°C. IR spectrum,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 3 2008

GIMALOVA et al.
324
residue was recrystallized from ethyl acetate–petrole-
um ether (1:10). Yield of compound V 0.24 g (~67%).
extracted with chloroform (4×5 ml). The extracts were
combined, washed with a saturated solution of NaCl,
dried over MgSO4, and evaporated. Yield 0.06 g
2-Benzyl-2,5-dichloro-4-hydroxycyclopent-4-ene-
1,3-dione (V). Pale pink crystals, mp 157–160°C
(from diethyl ether). IR spectrum, ν, cm–1: 509, 601,
706, 748, 850, 1034, 1152, 1261, 1315, 1359, 1458,
1
(60%), oily substance. H NMR spectrum, δ, ppm:
2.20 d (1H, OH, J = 10.50 Hz), 3.32 d (1H, J =
14.50 Hz) and 3.43 d (1H, CH2, J = 14.90 Hz), 3.48 s
(3H) and 3.57 s (3H, OCH3), 4.40 d (1H, OCH, J =
10.41 Hz), 7.31 m (5H, C6H5). 13C NMR spectrum, δC,
ppm: 42.49 (CH2); 51.25, 51.96 (OMe); 77.25 (C1);
81.85 (C5); 104.93 (C4); 127.03, 127.61, 130.98, 135.17
(Carom); 136.12 (C2, C3).
1
1622, 1641, 1701, 1761, 3061, 3088, 3446. H NMR
spectrum (acetone-d6), δ, ppm: 3.44 d.d (2H, CH2,
J = 13.1, 8.3 Hz), 6.99 br.s (2H) and 7.23 m (3H,
C6H5). 13C NMR spectrum (acetone-d6), δC, ppm: 40.83
(CH2); 63.49 (C2); 126.15 (C5); 127.67, 128.30, 129.66,
132.47 (Carom); 164.21 (C4); 186.28, 189.07 (C1, C3).
5-Benzyl-2,3,5-trichloro-4-hydroxycyclopent-2-
en-1-one (IX). A solution of 0.14 g (0.42 mmol) of
compound VIII in 1 ml of acetonitrile was cooled to
0°C, 0.3 g (2.92 mmol) of concentrated sulfuric acid
was added dropwise, and the mixture was heated to
35°C, stirred for 3 h at that temperature, cooled, and
treated with 3 ml of ice water. Solid sodium carbonate,
0.2 g, was then added in portions, and the mixture was
stirred for 5–10 min and extracted with diethyl ether
(3×5 ml). The extracts were combined, dried over
MgSO4, and evaporated, and the residue was subjected
to flash chromatography on silica gel using ethyl
acetate–petroleum ether (1:1) as eluent. Yield 0.08 g
2,3,3a,8a-Tetrachloro-8,8a-dihydrocyclopenta-
[a]inden-1-one (VI). Colorless crystals, mp 105–
106.5°C (from diethyl ether). IR spectrum, ν, cm–1:
673, 702, 887, 1132, 1192, 1238, 1377, 1463, 1587,
1
1753. H NMR spectrum, δ, ppm: 3.64 d (1H, J =
17.98 Hz) and 3.85 d (1H, CH2, J = 17.97 Hz); 7.22–
7.42 m (2H), 7.42 m (1H), and 7.73 m (1H, C6H4).
13C NMR spectrum, δC, ppm: 42.98 (CH2); 74.75 (C8a);
80.78 (C3a); 125.21, 125.64, 128.73, 131.33, 136.96,
138.49 (Carom); 131.52 (C2); 161.02 (C3); 188.49
(C=O). Mass spectrum, m/z: 306, 308, 310 [M]+, 271,
273, 275 [M – Cl]+, 236, 238 [M – 2Cl]+, 243 [M –
Cl – CO]+, 173 [M – CO – 3Cl]+.
1
(~70%), pale yellow oily substance. H NMR spec-
trum, δ, ppm: 2.71 d (2H, OH, J = 10.60 Hz), 3.36 d
(1H, J = 14.0 Hz) and 3.64 d (1H, CH2, J = 14.0 Hz),
4.79 d (1H, OCH, J = 10.60 Hz), 7.21 m (2H) and
7.32 m (3H, C6H5). 13C NMR spectrum, δC, ppm:
41.42 (CH2); 72.67 (C4); 73.99 (C5); 128.01, 129.02,
130.58, 133.33 (Carom); 131.92 (C2); 161.66 (C3);
189.01 (C1).
2-Benzyl-2,5-dichloro-4-methoxycyclopent-4-
ene-1,3-dione (VII) was obtained by treatment of
0.1 g (0.36 mmol) of compound V with diazomethane.
1
Yield 0.1 g (>95%), yellow oily substance. H NMR
spectrum, δ, ppm: 3.49 d.d (2H, CH2, J = 16.1,
13.0 Hz), 4.26 s (3H, OCH3), 7.03 m (2H) and 7.24 m
(3H, C6H5). 13C NMR spectrum, δC, ppm: 41.59 (CH2);
60.68 (OCH3); 63.97 (C2); 127.40 (C5); 128.18, 128.85,
129.98, 132.40 (Carom); 163.19 (C4); 186.71, 189.09
(C1, C3).
REFERENCES
1. Akhmetvaleev, R.R., Akbutina, F.A., Ivanova, N.A., and
Miftakhov, M.S., Izv. Ross. Akad. Nauk, Ser. Khim., 2001,
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2. Ivanova, N.A., Shainurova, A.M., Spirikhin, L.V., and
Miftakhov, M.S., Izv. Ross. Akad. Nauk, Ser. Khim., 1998,
p. 2552.
5-Benzyl-2,3,5-trichloro-4,4-dimethoxycyclo-
pent-2-en-1-ol (VIII). A suspension of 0.02 g
(0.59 mmol) of NaBH4 in 5 ml of methanol was cooled
to 0°C, a solution of 0.1 g (0.59 mmol) of compound
II in 3 ml of ethanol was added, and the mixture was
stirred until the initial compound disappeared (TLC).
The mixture was treated with 2 ml of water, the
organic solvent was evaporated, and the residue was
3. Ivanova, N.A., Shainurova, A.M., and Miftakhov, M.S.,
Russ. J. Org. Chem., 2000, vol. 36, p. 434.
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 3 2008