Direct synthesis of 2,3,5-trichloro-4,4-dimethoxy-and 2,5-dichloro-3,4,4- trimethoxycyclopent-2-en-1-ones from hexachlorocyclopentadiene and some aspects of their reactivity

Article abstract of DOI:10.1134/S1070428008090042

2,3,5-Trichloro-4,4-dimethoxy-and 2,5-dichloro-3,4,4-trimethoxycyclopent-2- en-1-ones were synthesized directly by treatment of hexachlorocyclopentadiene with methanol in the presence of potassium hydroxide at room temperature or on heating and subsequent

Full text of DOI:10.1134/S1070428008090042

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 9, pp. 1271–1277. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © N.A. Ivanova, K.S. Kislitsina, M.S. Miftakhov, 2008, published in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 9,
pp. 1287–1293.
Direct Synthesis of 2,3,5-Trichloro-4,4-dimethoxy-
and 2,5-Dichloro-3,4,4-trimethoxycyclopent-2-en-1-ones
from Hexachlorocyclopentadiene and Some Aspects
of Their Reactivity
N. A. Ivanova, K. S. Kislitsina, 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 July 17, 2007
Abstract—2,3,5-Trichloro-4,4-dimethoxy- and 2,5-dichloro-3,4,4-trimethoxycyclopent-2-en-1-ones were syn-
thesized directly by treatment of hexachlorocyclopentadiene with methanol in the presence of potassium
hydroxide at room temperature or on heating and subsequent acidification of the reaction mixture. Reactions of
2,3,5-trichloro-4,4-dimethoxycyclopent-2-en-1-one with some reducing agents and nucleophiles were studied.
DOI: 10.1134/S1070428008090042
Highly functionalized cyclopentane building blocks
possess a broad synthetic potential and are promising
for subsequent versatile transformations; they are quite
valuable initial compounds for the synthesis of cyclo-
pentane derivatives. Such compounds are oxygenated
chlorocyclopentenones I which were obtained by us
previously from hexachlorocyclopentadiene [1]. They
attract interest as key intermediate products in the syn-
thesis of chlorine-containing natural compounds (such
as chlorovulones [2], punaglandins, cryptosporiopsin
[3], etc.), design of heterocycles and new bioactive
cyclopentanoids, etc. In continuation of our studies in
this line, the present article reports on a practical
procedure for the preparation of the simplest chloro-
cyclopentenone building block II and new cyclopen-
tanetrione derivative, 2,5-dichloro-3,4,4-trimethoxy-
cyclopent-2-en-1-one (III), using low-expensive tech-
nical chemicals (KOH, MeOH, H2SO4) and some reac-
tions of trichlorocyclopentenone II.
In the synthesis of cyclopentenone II, a mixture of
hexachlorocyclopentadiene and potassium hydroxide
at a ratio of 1:(7–10) in methanol was stirred for 10 h
at 55°C, cooled to 0°C, acidified with 50% sulfuric
acid, and stirred for 8 h at 60°C. After appropriate
treatment of the reaction mixture, chlorocyclopen-
tenone II was isolated by vacuum distillation in more
than 70% yield (Scheme 1). This one-step procedure is
simpler and more practical than the known methods
[5–7]. By carrying out analogous reaction under more
severe conditions (70–80°C), the reactant ratio and
concentrations remaining the same, we obtained previ-
ously unknown trimethoxycyclopentenone III.
Compound II was brought into several transforma-
tions typical of trichlorocyclopentenones I (Scheme 2)
[1]. Trichlorocyclopentenone II was readily reduced
with sodium tetrahydridoborate to produce stereo-
chemically pure cyclopentenol IV in a high yield. The
cis orientation of the hydroxy group and chlorine atom
O
O
O
R
Cl
Cl
Cl
Cl
Cl
Cl
OMe
OMe
OMe
Cl
Cl
MeO
OMe
OMe
OMe
I
II
III
R = aryl, furyl, allenyl, benzyl, etc.
1271

IVANOVA et al.
1272
Scheme 1.
O
(1) KOH–MeOH, 55°C, 10 h
(2) H+, H2O, 60°C, 8 h
Cl
Cl
Cl
OMe
Cl
Cl
Cl
OMe
Cl
Cl
II
O
Cl
Cl
(1) KOH–MeOH, 70°C, 20 h
(2) H+, H2O, 60°C, 8 h
Cl
OMe
OMe
MeO
III
in the 5-position followed from the coupling constant
J1, 5 equal to 5.0 Hz in H NMR spectrum [8]. The
same product was obtained by reduction of II with
NaBH(OAc)3, but in this case the reaction required
more severe conditions (boiling tetrahydrofuran).
Chemoselective hydrodechlorination of trichloro-
ketone II with formation of expected dichlorocyclo-
pentenone V was effected by the action of CrCl2 [9].
Analogous reactions with zinc in methanol in the
absence and in the presence of ammonium chloride
were less effective. In the first case, the conversion of
II did not exceed 70%, and in the second, compound
III was formed as by-product (Scheme 2).
to the corresponding aminocyclopentenones VI–VIII.
With a view to extend the series of nucleophiles, we
examined reactions of II with oxygen, sulfur, and
phosphorus reagents (Scheme 3). Strong nucleophiles,
such as sodium benzenethiolate and sodium methoxide
reacted with trichlorocyclopentenone II to give prod-
ucts of replacement of the chlorine atom at C3 (addi-
tion–elimination pattern), sulfide IX and trimethoxy-
cyclopentenone III, respectively. In the reaction with
a neutral nucleophile, triethyl phosphite, the process
followed the Arbuzov reaction scheme with formation
of phosphonate X as result of replacement of the
5-chlorine atom.
1
Reactions of trichlorocyclopentenone II with nitro-
gen-centered nucleophiles, such as methylamine, di-
methylamine, and (+)-1-phenylethanamine, followed
the nucleophilic addition–elimination pattern, leading
We also performed deketalization of trichlorocyclo-
pentenone II and cyclopentenol IV. Compound II did
not change under standard acid hydrolysis conditions.
We succeeded in obtaining symmetric diketone XI
Scheme 2.
OH
O
NaBH4, MeOH, 0°C, 2 h
or NaBH(OAc)3, THF, Δ, 10 h
Cl
Cl
Cl
Cl
MeNH2 ·HCl, KOH, MeOH
Me2NH·HCl, KOH, MeOH
(+)-PhCH(Me)NH2, PhH
OMe
OMe
Cl
MeNH
OMe
OMe
IV
VI
O
O
CrCl2, Me2CO/HCl, 5 h
or Zn, MeOH, Δ, 24 h
Cl
Cl
Cl
II
OMe
OMe
Cl
Me2N
OMe
OMe
V
VII
O
Cl
Cl
Zn–NH4Cl, MeOH, 20°C, 2 h
III
+ V
Ph
OMe
OMe
NH
Me
VIII
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 9 2008

DIRECT SYNTHESIS OF 2,3,5-TRICHLORO-4,4-DIMETHOXY-...
Scheme 3.
1273
EXPERIMENTAL
O
The IR spectra were recorded on UR-20 and
Specord M-80 instruments from samples prepared as
films (neat) or dispersed in mineral oil. The 1H and 13C
NMR spectra were measured on a Bruker AM-300
spectrometer at 300.13 and 75.47 MHz, respectively,
using CDCl3 as solvent and reference (δ 7.27 ppm,
δC 77.00 ppm). The mass spectra (electron impact, 20
or 70 eV) were obtained on an MKh-1306 instrument,
ion source temperature 75–100°C. The progress of re-
actions was monitored by TLC on Silufol plates using
hexane–ethyl acetate as eluent; spots were detected by
treatment with an alkaline solution of potassium per-
manganate [11].
Cl
Cl
KOH, MeOH, 20°C
OMe
MeO
OMe
III
O
Cl
Cl
PhSH, MeONa, 20°C
II
OMe
PhS
OMe
IX
O
Cl
P(O)(OEt)2
2,3,5-Trichloro-4,4-dimethoxycyclopent-2-en-1-
one (II). A mixture of 27.3 g (0.1 mol) of hexachloro-
cyclopentadiene and 56.0 g (1.0 mol) of potassium
hydroxide in 250 ml of methanol was stirred for 24 h
at room temperature. The mixture was then cooled to
0°C, 50% sulfuric acid was slowly added under stirring
to pH 1, the mixture was stirred for 10 h at 50°C, and
the precipitate (NaCl) was filtered off. The filtrate was
concentrated under reduced pressure and extracted
with ethyl acetate (3×50 ml). The combined extracts
were washed with a 10% aqueous solution of sodium
hydrogen carbonate and a saturated solution of sodium
chloride, dried over MgSO4, and concentrated, and the
residue was distilled under reduced pressure, a fraction
boiling at 100–103°C (0.2 mm) being collected. Yield
18.4 g (75%), colorless oily substance, which crystal-
lized on storage to form colorless crystals with mp 52–
54°C, Rf 0.42 (petroleum ether–ethyl acetate, 9:1). IR
(EtO)3P, MeCN, 50°C
OMe
Cl
OMe
X
only after prolonged keeping of II in concentrated
sulfuric acid [10] (Scheme 4). By contrast, chloro-
cyclopentenol IV was readily hydrolyzed in aqueous–
organic medium in the presence of a mineral acid
(Scheme 4). The reaction was accompanied by cis–
trans isomerization; the major product was trans
isomer XII (J4,5 = 2.5 Hz), while the fraction of cis
isomer XIII did not exceed 10% (according to the
1H NMR data).
Thus we have developed a preparatively convenient
one-pot procedure for the transformation of hexa-
chlorocyclopentadiene into functionalized chlorometh-
oxycyclopentenones II and III that are attractive from
the synthetic viewpoint. Their synthetic potential has
been demonstrated by various reactions of 2,3,5-tri-
chloro-4,4-dimetoxycyclopent-2-en-1-one (II).
1
spectrum, ν, cm–1: 1050, 1596, 1636, 1752. H NMR
spectrum, δ, ppm: 3.53 s (3H, OCH3), 3.51 s (3H,
OCH3), 4.64 s (1H, 5-H). 13C NMR spectrum, δC, ppm:
52.03 (OCH3), 52.07 (OCH3), 62.19 (C5), 100.49 (C4),
Scheme 4.
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
H2SO4 (concd.), 0°C
OMe
OMe
Cl
Cl
O
II
XI
OH
OH
OH
Cl
Cl
Cl
Cl
Cl
Cl
20% HCl–Me2CO, 20°C
+
OMe
OMe
Cl
Cl
O
Cl
O
IV
XII
9:1
XIII
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 9 2008

IVANOVA et al.
1274
133.77 (C2), 157.65 (C3), 186.17 (C1). Mass spectrum,
m/z (Irel , %): 249 (7.5), 247 (22.3), 245 (27.3) [M]+,
218 (31.4), 216 (93.6), 214 (100) [M – OCH3]+, 212
(19.8), 210 (30.9) [M – Cl]+, 190 (4.9), 188 (14.0), 186
(15.5) [M – CH3O – CO]+, 136 (6.1), 134 (13.8), 112
(2.5), 110 (9.7), 108 (13.3), 97 (31.9), 89 (7.4), 87
(22.8), 69 (11.9), 59 (17.7) [OCOCH3]+, 55 (11.1), 41
(8.0), 38 (5.5), 36 (14.8) [HCl]+, 28 (23.9). Found, %:
C 34.10; H 2.82; Cl 43.46. C7H7Cl3O3. Calculated, %:
C 34.25; H 2.87; Cl 43.33.
The solvent was distilled off under reduced pressure,
a saturated solution of sodium chloride was added to
the residue, and the mixture was extracted with ethyl
acetate (3×10 ml). The combined extracts were washed
with a saturated solution of sodium chloride, dried
over MgSO4, and concentrated, and the residue was
subjected to column chromatography on silica gel
using petroleum ether–ethyl acetate (7:3) as eluent.
Yield 0.19 g (95%), colorless crystals, mp 82–84°C,
Rf 0.57 (petroleum ether–ethyl acetate, 7:3, double
elution). IR spectrum, ν, cm–1: 1090, 1640, 3400.
1H NMR spectrum, δ, ppm: 2.56 d (1H, OH, J =
10.5 Hz), 3.46 s (3H, OCH3), 3.47 s (3H, OCH3),
4.50 d (1H, 5-H, J = 5.0 Hz), 4.65 d.d (1H, 1-H, J =
2,5-Dichloro-3,4,4-trimethoxycyclopent-2-en-1-
one (III). a. Following an analogous procedure, a mix-
ture of 3.0 g (0.01 mol) of hexachlorocyclopentadiene
and 4.2 g (0.08 mol) of potassium hydroxide in 10 ml
of methanol was heated for 10 h at 70–80°C. After
standard treatment, the residue was subjected to
column chromatography on silica gel using petroleum
ether–ethyl acetate (8:2) as eluent to isolate 2.40 g
(80%) of compound III as a yellow oily substance,
Rf 0.31 (petroleum ether–ethyl acetate, 9:1, double
elution).
13
10.5, 5.0 Hz). C NMR spectrum, δC, ppm: 50.81 and
51.89 (OCH3), 65.33 (C5), 73.13 (C1), 103.97 (C4),
130.86 (C3), 136.09 (C2). Found, %: C 33.83; H 3.54;
Cl 42.86. C7H9Cl3O3. C7H9Cl3O3. Calculated, %:
C 33.97; H 3.67; Cl 42.97.
b. A solution of 0.1 g (0.4 mmol) of trichlorocyclo-
pentenone II in 3 ml of anhydrous THF was cooled to
0°C, 0.75 g (2 mmol) of NaBH(OAc)3 was added
under argon, and the mixture was stirred for 5 h at
room temperature. The mixture was diluted with 5 ml
of acetone and treated as described above in a to
isolate 0.08 g (80%) of compound IV.
b. A solution of 6.72 g (12.0 mmol) of potassium
hydroxide in 50 ml of methanol was added under stir-
ring to a solution of 1.0 g (4.0 mmol) of trichlorocyclo-
pentenone II in 30 ml of methanol, and the mixture
was stirred at room temperature until the initial com-
pound disappeared completely (2 h, TLC). The solvent
was distilled off under reduced pressure, a saturated
solution of sodium chloride was added to the residue,
and the mixture was neutralized with 10% hydro-
chloric acid to pH 7 and extracted with ethyl acetate
(3×10 ml). The combined extracts were washed with
a saturated solution of NaCl, dried over MgSO4, and
concentrated, and the residue was subjected to column
chromatography on silica gel using petroleum ether–
ethyl acetate (8:2) as eluent. Yield 0.78 g (88 %). IR
2,3-Dichloro-4,4-dimethoxycyclopent-2-en-1-one
(V). a. An aqueous solution of CrCl2 [9], 30 ml, was
added to a solution of 6.0 g (24.1 mmol) of trichloro-
cyclopentenone II in 60 ml of acetone under stirring at
20°C in a stream of argon. The mixture was stirred for
3 h (TLC), the precipitate was filtered off, the filtrate
was concentrated under reduced pressure, a saturated
solution of sodium chloride was added to the residue,
and the mixture was extracted with ethyl acetate (3×
30 ml). The combined extracts were washed with
a 10% aqueous solution of sodium hydrogen carbonate
to pH 7 and a saturated solution of sodium chloride,
dried over MgSO4, and concentrated. The product was
isolated by column chromatography on silica gel using
petroleum ether–ethyl acetate (9:1) as eluent. Yield
5.0 g (96%), yellow oily substance, Rf 0.33 (petroleum
ether–ethyl acetate, 9:1, double elution). IR spectrum,
ν, cm–1: 1080, 1600, 1740. 1H NMR spectrum, δ, ppm:
1
spectrum, ν, cm–1: 1080, 1610, 1740. H NMR spec-
trum, δ, ppm: 3.46 s (3H, OCH3), 3.50 s (3H, OCH3),
13
4.42 s (3H, OCH3), 4.48 s (1H, 5-H). C NMR spec-
trum, δC, ppm: 51.70 and 52.02 (OCH3), 57.79 (OCH3),
60.44 (C5), 100.13 (C4), 108.14 (C2), 171.94 (C3),
187.05 (C1). Found, %: C 39.83; H 4.06; Cl 29.30.
C8H10Cl2O4. Calculated, %: C 39.86; H 4.18; Cl 29.41.
13
2.81 s (2H, 5-H), 3.65 s (6H, OCH3). C NMR spec-
1r,5c-2,3,5-Trichloro-4,4-dimethoxycyclopent-2-
en-1-ol (IV). a. A solution of 0.2 g (0.8 mmol) of tri-
chlorocyclopentenone II in 10 ml of methanol was
cooled to 0°C, 0.11 g (2.4 mmol) of sodium tetrahy-
dridoborate was added, the mixture was stirred for
0.5 h at 0°C and for 1.5 h at room temperature, and
10 ml of acetone was added under continuous stirring.
trum, δC, ppm: 45.29 (C5), 51.26 and 51.28 (OCH3),
102.22 (C4), 134.99 (C2), 158.57 (C3), 191.30 (C1).
Found, %: C 39.76; H 3.96; Cl 33.46. C7H8Cl2O3. Cal-
culated, %: C 39.84; H 3.82; Cl 33.60.
b. Trichlorocyclopentenone II, 0.1 g (4.1 mmol),
was dissolved in 5 ml of methanol, 0.92 g (16.4 mmol)
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 9 2008

DIRECT SYNTHESIS OF 2,3,5-TRICHLORO-4,4-DIMETHOXY-...
1275
of zinc dust and 0.05 g of ammonium chloride were
added under stirring, and the mixture was stirred for
1 h on heating under reflux. The precipitate was fil-
tered off, the solvent was distilled off from the filtrate
under reduced pressure, a saturated solution of sodium
chloride was added to the residue, and the mixture was
extracted with ethyl acetate (3×5 ml). After standard
treatment, column chromatography on silica gel using
petroleum ether–ethyl acetate (9 :1) as eluent gave
0.04 g (45%) of dichlorocyclopentenone V.
ethyl acetate (1:1) as eluent. Yield 0.16 g (76%),
yellow crystals, mp 89–90°C, Rf 0.4 (petroleum ether–
ethyl acetate, 1:1). IR spectrum, ν, cm–1: 1080, 1360,
1
1400, 1600, 1705. H NMR spectrum, δ, ppm: 3.27 s
(3H, OCH3), 3.37 br.s (6H, NMe2), 3.52 s (3H, OCH3),
13
4.59 s (1H, 5-H). C NMR spectrum, δC, ppm: 41.74
(NMe2), 51.49 and 52.88 (OCH3), 60.72 (C5), 102.57
(C2), 103.29 (C4), 159.68 (C3), 183.84 (C1). Found, %:
C 42.65; H 5.02; Cl 27.78; N 5.38. C9H13Cl2NO3. Cal-
culated, %: C 42.54; H 5.16; Cl 27.90; N 5.51.
2,5-Dichloro-4,4-dimethoxy-3-methylamino-
cyclopent-2-en-1-one (VI). Trichlorocyclopentenone
II, 0.2 g (0.8 mmol), was dissolved in 5 ml of metha-
nol, 0.27 g (4 mmol) of methylamine hydrochloride
and 0.22 g (4 mmol) of potassium hydroxide were
added at 20°C, and the mixture was stirred for 2 h at
room temperature. The solvent was distilled off under
reduced pressure, the residue was treated with 5 ml of
a saturated solution of sodium chloride, and the mix-
ture was extracted with ethyl acetate (3×10 ml). The
combined extracts were washed with 10% hydro-
chloric acid to pH 7 and with a saturated solution of
sodium chloride, dried over MgSO4, and concentrated,
and the product was isolated by column chromatog-
raphy on silica gel using petroleum ether–ethyl acetate
(1:1) as eluent. Yield 0.13 g (66%), colorless crystals,
mp 95–96°C, Rf 0.4 (petroleum ether–ethyl acetate,
1:1). IR spectrum, ν, cm–1: 1080, 1360, 1600, 1705,
2,5-Dichloro-4,4-dimethoxy-3-(1-phenylethyl-
amino)cyclopent-2-en-1-one (VIII). (+)-1-Phenyl-
ethanamine, 0.13 ml (1.6 mmol), was added at 20°C
under stirring in a stream of argon to a solution of
0.2 g (0.8 mmol) of trichlorocyclopentenone II in 3 ml
of anhydrous benzene, and the mixture was stirred for
1.5 h. The solvent was distilled off under reduced pres-
sure, the residue was treated with a saturated solution
of sodium chloride, and the mixture was extracted with
ethyl acetate (3×10 ml). The combined extracts were
washed with a saturated solution of sodium chloride,
dried over MgSO4, and concentrated, and the product
was isolated by column chromatography on silica gel
using petroleum ether–ethyl acetate (1:1) as eluent.
Yield 0.15 g (55%), orange oily substance, Rf 0.63
(petroleum ether–ethyl acetate, 1:1). IR spectrum, ν,
1
cm–1: 1000, 1080, 1580, 1620, 1710, 3300. H NMR
spectrum, δ, ppm: 1.65 d (3H, CH3, J = 6.7 Hz), 3.42 s
and 3.48 s (3H each, OCH3), 4.42 s (1H, 5-H), 5.60 q
(1H, NCH, J = 6.7 Hz), 5.75 m (1H, NH), 7.30–7.40 m
(5H, C6H5). 13C NMR spectrum, δC, ppm: 23.22 (CH3);
51.83 and 52.59 (OCH3); 59.90 (NCH); 60.16 (C5);
98.10 (C2); 100.75 (C4); 125.66, 127.71, and 128.77
(Carom); 142.01 (C2); 142.2 (Ci); 158.82 (C3); 185.45
(C1). Found, %: C 54.63; H 5.23; Cl 21.64; N 4.16.
C15H17Cl2NO3. Calculated, %: C 54.56; H 5.19;
Cl 21.47; N 4.24.
1
3320. H NMR spectrum, δ, ppm: 1.65 s (3H, NCH3),
3.35 s (3H, OCH3), 3.45 s (3H, OCH3), 4.59 s (1H,
5-H), 7.10 br.s (1H, NH). 13C NMR spectrum, δC, ppm:
30.09 (NCH3), 51.49 and 52.88 (OCH3), 60.51 (C5),
96.47 (C2), 100.23 (C4), 160.61 (C3), 183.72 (C1).
Found, %: C 40.14; H 4.54; Cl 29.67; N 5.74.
C8H11Cl2NO3. Calculated, %: C 40.02; H 4.62;
Cl 29.5; N 5.83.
2,5-Dichloro-3-dimethylamino-4,4-dimethoxy-
cyclopent-2-en-1-one (VII). Trichlorocyclopentenone
II, 0.2 g (0.8 mmol), was dissolved in 5 ml of metha-
nol, 0.13 g (1.6 mmol) of dimethylamine hydro-
chloride and 0.1 g (1.6 mmol) of potassium hydroxide
were added under stirring at 20°C, and the mixture was
stirred for 2 h at room temperature. The solvent was
distilled off under reduced pressure, the residue was
treated with 5 ml of a saturated solution of sodium
chloride, and the mixture was extracted with ethyl
acetate (3×10 ml). The combined extracts were washed
with 10% hydrochloric acid to pH 7 and with a saturat-
ed solution of sodium chloride, dried over MgSO4, and
concentrated, and the product was isolated by column
chromatography on silica gel using petroleum ether–
2,5-Dichloro-4,4-dimethoxy-3-phenylsulfanyl-
cyclopent-2-en-1-one (IX). Benzenethiol, 0.12 ml
(1.1 mmol), was added dropwise under stirring to a so-
lution of 0.06 g (1 mmol) of sodium methoxide in 3 ml
of anhydrous methanol, the mixture was kept for
20 min, and the resulting solution of sodium benzene-
thiolate was added to a solution of 0.5 g (2.0 mmol) of
trichlorocyclopentenone II in 10 ml of anhydrous
methanol. When the reaction was complete (3 h; TLC,
petroleum ether–ethyl acetate, 8:2), the mixture was
treated with a saturated solution of sodium chloride,
the solvent was distilled off under reduced pressure,
and the product was extracted into ethyl acetate (3×
10 ml). The combined extracts were washed with a sat-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 9 2008

IVANOVA et al.
1276
urated solution of sodium chloride, dried over MgSO4,
and concentrated, and the residue was recrystallized
from petroleum ether (bp 40–70°C). Yield 0.65 g
(90%). Colorless crystals, mp 80–82°C, Rf 0.34 (pe-
troleum ether–ethyl acetate, 8:2). IR spectrum, ν,
C 30.24; H 0.59; Cl 53.41. C5HCl3O2. Calculated, %:
C 30.11; H 0.51; Cl 53.33.
2,3,5β-Trichloro-4α-hydroxycyclopent-2-en-1-
one (XII) and 2,3,5α-trichloro-4α-hydroxycyclo-
pent-2-en-1-one (XIII). Trichlorocyclopentenol IV,
1.0 g (0.8 mmol), was dissolved in 30 ml of acetone,
and 15% hydrochloric acid was added dropwise under
stirring until pH 1. The mixture was stirred at room
temperature until the initial compound disappeared
completely (3 h; TLC, petroleum ether–ethyl acetate,
7:3) and neutralized with a 10% aqueous solution of
sodium hydrogen carbonate to pH 7. The solvent was
distilled off under reduced pressure, the residue was
treated with a saturated solution of sodium chloride,
and the mixture was extracted with ethyl acetate (3×
15 ml). The combined extracts were washed with a sat-
urated solution of sodium chloride, dried over MgSO4,
and concentrated, and the residue was subjected to
column chromatography on silica gel using petroleum
ether–ethyl acetate (8:2) as eluent to isolate 0.7 g
(90%) of a mixture of stereoisomers XII and XIII at
a ratio of 9:1.
1
cm–1: 1060, 1550, 1590, 1730. H NMR spectrum, δ,
ppm: 3.49 s (3H, OCH3), 3.50 s (3H, OCH3), 4.52 s
(1H, 5-H), 7.40 m (3H, Harom), 7.55 m (2H, Harom).
13C NMR spectrum, δC, ppm: 51.70 and 52.15 (OCH3);
61.43 (C5); 103.65 (C4); 126.44, 128.96, 130.00, and
134.65 (Carom); 129.48 (C2); 162.93 (C3); 187.05 (C1).
Found, %: C 48.80; H 3.92; Cl 22.35; S 10.18.
C13H12Cl2O3S. Calculated, %: C 48.92; H 3.79;
Cl 22.21; S 10.05.
Diethyl (3,4-dichloro-5,5-dimethoxy-2-oxocyclo-
pent-3-en-1-yl)phosphonate (X). Triethyl phosphite,
0.33 ml (1.6 mmol), was added under stirring to a solu-
tion of 0.2 g (0.8 mmol) of trichlorocyclopentenone II
in 3 ml of anhydrous acetonitrile, and the mixture was
stirred for 5 h at 50°C. The solvent was distilled off
under reduced pressure, the residue was treated with
a saturated solution of sodium chloride, and the prod-
uct was extracted into ethyl acetate (3×10 ml). The
combined extracts were washed with a saturated solu-
tion of sodium chloride, dried over MgSO4, and con-
centrated, and the residue was subjected to column
chromatography on silica gel using chloroform–metha-
nol (50:1 to 30:1) as eluent to isolate 0.07 g (30%) of
phosphonate X as a yellow oily substance, Rf 0.34
(petroleum ether–ethyl acetate, 1:1). IR spectrum, ν,
2,3,5β-Trichloro-4α-hydroxycyclopent-2-en-1-
one (XII). Yellow oily substance, Rf 0.42 (petroleum
ether–ethyl acetate, 8:2, double elution). IR spectrum,
1
ν, cm–1: 1089, 1636, 1747, 3440. NMR spectrum, δ,
ppm: 3.58 d (1H, OH, J = 5.3 Hz), 4.43 d (1H, 5-H,
J = 2.5 Hz), 4.95 d.d (1H, 4-H, J = 2.5, 5.3 Hz).
13C NMR spectrum, δC, ppm: 60.92 (C5), 78.51 (C4),
132.78 (C2), 161.71 (C3), 188.20 (C1). Found, %:
C 29.98; H 1.39; Cl 52.67. C5H3Cl3O2. Calculated, %:
C 29.81; H 1.50; Cl 52.80.
1
cm–1: 1031, 1269, 1638. H NMR spectrum, δ, ppm:
1.38 t (6H, CH3, J = 4.5 Hz), 3.42 s (6H, OCH3),
4.25 q (4H, OCH2, J = 7 Hz), 5.79 s (1H, 5-H). Found,
%: C 38.24; H 4.83; Cl 20.35; P 9.05. C11H17Cl2O6P.
Calculated, %: C 38.06; H 4.94; Cl 20.43; P 8.92.
2,3,5α-Trichloro-4α-hydroxycyclopent-2-en-1-
one (XIII). Yellow oily substance, Rf 0.31 (petroleum
ether–ethyl acetate, 8:2, double elution). IR spectrum,
ν, cm–1: 1090, 1616, 1738, 3430. 1H NMR spectrum, δ,
ppm: 4.72 d (1H, 5-H, J = 5.8 Hz), 5.00 d (1H, 4-H,
2,4,5-Trichlorocyclopent-4-ene-1,3-dione (XI).
A mixture of 0.1 g (0.4 mmol) of trichlorocyclopen-
tenone II and 3 ml of concentrated sulfuric acid was
kept for 1 h at 0°C. The product was extracted into
chloroform (3 ×5 ml), the combined extracts were
neutralized with a saturated solution of sodium hydro-
gen carbonate, washed with a saturated solution of
sodium chloride, dried over MgSO4, and concentrated,
and the residue was subjected to column chromatog-
raphy on silica gel using chloroform–methanol (9:1)
as eluent. Yield 0.08 g (90%), brown oily substance,
Rf 0.73 (chloroform–methanol, 9:1). IR spectrum, ν,
13
J = 5.8 Hz). C NMR spectrum, δC, ppm: 57.66 (C5),
70.33 (C4), 129.88 (C2), 158.78 (C3), 183.72 (C1).
REFERENCES
1. Akhmetvaleev, R.R., Akbutina, F.A., Ivanova, N.A., and
Miftakhov, M.S., Izv. Ross. Akad. Nauk, Ser. Khim., 2001,
no. 9, p. 1417.
2. Iguchi, K., Kaneta, S., Yamada, Y., Honda, A., and
Mori, Y., Tetrahedron Lett., 1985, vol. 26, p. 5787.
3. Suzuki, M., Morita, Y., Yanagisawa, A., Baker, B.J.,
Scheuer, P.J., and Noyori, R., J. Org. Chem., 1988,
vol. 53, p. 286.
1
cm–1: 1458, 1605, 1720, 1740. H NMR spectrum:
δ 4.76 ppm, s (1H, 2-H). 13C NMR spectrum, δC, ppm:
4. McGahren, W.J., van den Hende, J.H., and
62.58 (C2), 151.17 (C4, C5), 183.78 (C1, C3). Found, %:
Mitscher, L.A., J. Am. Chem. Soc., 1969, vol. 91, p. 157.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 9 2008

DIRECT SYNTHESIS OF 2,3,5-TRICHLORO-4,4-DIMETHOXY-...
1277
5. Zefirov, N.S., Kirpichenok, M.A., and Shestakova, T.G.,
9. Rosenkranz, G., Manzera, O., Gatica, I., and Djeras-
Zh. Org. Khim., 1983, vol. 19, p. 535.
si, K., J. Am. Chem. Soc., 1950, vol. 72, p. 4077.
6. Zefirov, N.S., Kirpichenok, M.A., and Shestakova, T.G.,
10. von Roedig, A., and Markl, G., Justus Liebigs Ann.
Chem., 1962, vol. 659, p. 1.
Dokl. Akad. Nauk SSSR, 1982, vol. 262, p. 890.
7. Akhmetvaleev, R.R., Imaeva, L.R., and Miftakhov, M.S.,
Russ. J. Org. Chem., 1997, vol. 33, p. 1267.
8. Tolstikov, G.A., Ismailov, S.A., Vel’der, Ya.L., and Mif-
11. Kirchner, J.G., Thin-Layer Chromatography, Perry, E.S.,
Ed., New York: Wiley, 1978, 2nd ed. Translated under
the title Tonkosloinaya khromatografiya, Moscow: Mir,
1981, vol. 1, p. 269.
takhov, M.S., Zh. Org. Khim., 1990, vol. 26, p. 672.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 9 2008