Synthesis and biological activity of permethrinic acid analogs containing various substituents in position 2 of the cyclopropane ring

Article abstract of DOI:10.1134/S107042800808006X

A number of permethrinic acid ethyl ester derivatives having various substituents [Et, Pr, Ph, Ph(CH₂) _n (n = 1, 2), etc.] in position 2 of the cyclopropane ring were synthesized, and their insecticidal acivity against typhoid flies, rice weevils, and bean aphides, as well as juvenoid activity on flour beetle chrysalises, was studied. The newly synthesized compounds turned out to exhibit weak insecticidal activity against standard insects but pronounced juvenile hormone activity, which differentiates them from permethrinic acid esters.

Full text of DOI:10.1134/S107042800808006X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 8, pp. 1139–1149. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © N.S. Mirzabekova, N.E. Kuz’mina, O.I. Lukashov, N.A. Sokolova, S.N. Golosov, P.V. Kazakov, T.G. Perlova, V.V. Potapova, V.A.
Kheinman, G.B. Ivanova, 2008, published in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 8, pp. 1153–1163.
Synthesis and Biological Activity of Permethrinic Acid
Analogs Containing Various Substituents in Position 2
of the Cyclopropane Ring
N. S. Mirzabekovaa, N. E. Kuz’minaa, O. I. Lukashova, N. A. Sokolovaa, S. N. Golosova,
P. V. Kazakova, T. G. Perlovab, V. V. Potapovab, V. A. Kheinmanb, and G. B. Ivanovab
a State Research Institute of Organic Chemistry and Technology, shosse Entuziastov 23, Moscow, 111024 Russia
e-mail: nsm21@yandex.ru.
b All-Russian Research Institute of Chemical Means for Plant Protection, Moscow, Russia
Received July 12, 2007
Abstract—A number of permethrinic acid ethyl ester derivatives having various substituents [Et, Pr, Ph,
Ph(CH2)n (n = 1, 2), etc.] in position 2 of the cyclopropane ring were synthesized, and their insecticidal acivity
against typhoid flies, rice weevils, and bean aphides, as well as juvenoid activity on flour beetle chrysalises,
was studied. The newly synthesized compounds turned out to exhibit weak insecticidal activity against standard
insects but pronounced juvenile hormone activity, which differentiates them from permethrinic acid esters.
DOI: 10.1134/S107042800808006X
Pyrethroids are analogs of naturally occurring
pyrethrins (A) that are esters derived from substituted
cyclopropanecarboxylic acid; these compounds are
isolated from flowers of some Chrysanthemum spe-
cies, and they exhibit insecticidal activity.
other hand, the possibility for obtaining biologically
active pyrethroid structures with different functional
substituents in position 2 of the cyclopropane fragment
(trifluoromethyl, cyano, phenyl) was noted in some
publications [7–11].
With the goal of studying the structure–activity
relations in the series of cyclopropanecarboxylic acid
esters we synthesized permethrinic acid ethyl ester
[ethyl 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-
1-carboxylate] analogs containing various substituents
(alkyl and aralkyl groups) in position 2 of the cyclo-
propane ring. For this purpose, ketones I were brought
into reaction with ethyl (diethoxyphosphoryl)acetate to
obtain substituted acrylic acid ethyl esters II [12]
(Scheme 1). Selective reduction of the ester group in II
with lithium tetrahydridoaluminate [13] gave the corre-
sponding unsaturated alcohols III which were acylated
with triethyl orthoacetate; the reaction involved
Claisen-type rearrangement of intermediate acetal to
give ethyl pent-4-enoates IV [14]. Catalytic addition of
bromotrichloromethane at the double bond of esters IV
resulted in the formation of ethyl 4-bromo-6,6,6-tri-
chlorohexanoates V. Finally, dehydrohalogenation and
cyclization of esters V by the action of ethanolic
sodium ethoxide afforded the desired ethyl 2,2-disub-
stituted 3-(2,2-dichlorovinyl)cyclopropane-1-carbox-
ylates VI.
Me
Me
2
Me
Me
*
*
O
3
1
*
R
CH2
O
O
A
R = Me, MeOCO.
Published data on the synthesis and properties of
pyrethroids [1–5] indicate that all cyclopropanecar-
boxylic acid derivatives possessing strong insecticidal
activity have a common structural fragment, namely
geminal methyl groups in position 2 of the cyclo-
propane ring. The role of this structural fragment has
not been clearly understood. It was presumed that the
geminal methyl groups maintain spatial configuration
of the cyclopropane moiety in active molecules [2].
Both methyl groups are likely to be responsible for
biological activity of pyrethroids, for all known deriva-
tives having no methyl groups are inactive [6]. On the
1139

MIRZABEKOVA et al.
1140
Scheme 1.
EtO
EtO
OEt
t-BuOK
R1
OEt
LiAlH4
R1
OH
O
P
+
R1
R2
O
O
R2
O
R2
I
II
III
Br
R1
O
CH2
OEt
MeC(OEt)3, H+
CBrCl3
OEt
Cl3C
OEt
H2C
R1
R2
R1
R2
R2
O
O
IV
R2
V
R1
EtONa, EtOH
Cl2C
OEt
O
VI
R1, R2 = Me, Et, Pr, Ph, PhCH2, PhCH2CH2; R1R2 = (CH2)n, n = 4, 5.
The products were isolated from reaction mixtures
by standard procedures, including vacuum distillation,
crystallization, and chromatographic separation using
silica gel columns. The structure and purity of the iso-
lated compounds were determined using various ana-
lytical methods, such as thin-layer, liquid, and gas–
liquid chromatography, NMR spectroscopy, and mass
spectrometry.
ing was performed using threshold concentrations
determined for each kind of activity and each system-
atic group of insects and mites [19, 20]. The results
showed that replacement of two geminal methyl
groups in position 2 of the cyclopropane ring by other
alkyl, cycloalkyl, or ω-phenylalkyl groups leads to
compounds possessing a weak insecticidal activity
against test insects as compared to permethrinic acid
ethyl ester taken as reference. On the other hand,
unlike the latter, the examined compounds turned out
to exhibit pronounced juvenile hormone activity (score
5–7 according to Schmialek). The compounds also
showed weak phytotoxicity against plant leaves.
The structure of permethrinic acid ethyl ester ana-
logs VI was studied using one- and two-dimensional
1
NMR techniques (1H, 13C, DEPT, H 2D-COSY,
1
1H–13C 2D-CHCORR, H 2D-ROESY) [15, 16]. We
thus succeeded in assigning proton and carbon signals
to particular isomers. Stereoisomers of compounds
possessing two chiral centers were traditionally de-
noted as cis and trans. In compounds having three
chiral centers, the ester group was selected as refer-
ence, and orientation of the other substituents with
respect to the ester group was denoted by prefixes “c”
EXPERIMENTAL
The NMR spectra were recorded on a Bruker
Avance-300 spectrometer at 300 MHz using CDCl3 as
solvent and tetramethylsilane as internal reference. The
IR spectra were measured on a Perkin–Elmer 1720
spectrometer from solutions in carbon tetrachloride or
neat substances (film). The mass spectra (electron
impact) were obtained on a Fisons Trio 1000 GC–MS
system (quadrupole mass analyzer; SPB-1 capillary
column, 25 m×0.2 mm, stationary phase SE-54, film
thickness 0.35 μm; carrier gas helium). Gas–liquid
chromatography was performed on a Varian 3900 gas
chromatograph equipped with a flame-ionization de-
tector and a 15-m WCOT fused silica capillary column
(injector temperature 200°C, detector temperature
220°C; split ratio 100, flow rate 1 ml/min, carrier gas
nitrogen, 25 ml/min; hydrogen glow rate 25 ml/min,
air flow rate 300 ml/min). HPLC analysis was per-
1
and “t” [17]. The H and 13C NMR spectra of stereo-
isomers of compounds VIa–VIk are given in Experi-
1
mental.* The relations holding in the H and 13C
chemical shifts of substituents in the cyclopropane
ring, located cis and trans with respect to the ester
group, were described by us previously [18].
The isolated permethrinic acid ethyl ester analogs
were tested for enteric, systemic, and juvenile activity
in model insects (sensitive laboratory populations
belonging to different systematic groups) and for acari-
cidal activity in sensitive laboratory mites. The screen-
* The complete NMR spectra of the newly synthesized compounds
are available from the authors by e-mail: nsm21@yandex.ru.
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SYNTHESIS AND BIOLOGICAL ACTIVITY OF PERMETHRINIC ACID ANALOGS
1141
formed on a Millikhrom AO-2 liquid chromatograph
equipped with a spectrophotometric detector and a C18
reversed-phase column; eluents: A (aqueous phase):
90% buffer (100 ml of distilled water, 0.2 ml of 10%
trimethylamine, and 100 μg of heptanesulfonic acid) +
10% acetonitrile or distilled water without ionogenic
compounds (constant pH value); B (organic phase):
90% acetonitrile + 10% distilled water; the eluent
composition was programmed in a gradient mode (50
to 80% in 25 min, followed by keeping for 15 min).
The progress of reactions was monitored by TLC on
Silica gel 60 F254 plates (Merck) using hexane–ben-
zene (1:1) or benzene–diethyl ether (9:1) as eluent;
spots were visualized under UV light or by treatment
with a solution of phosphomolybdic acid. Ethyl
4-bromo-6,6,6-trichlorohexanoates V and ethyl cyclo-
propanecarboxylates VI were isolated from the reac-
tion mixtures by column chromatography on silica gel
60 (0.040–0.063 mm; Merck) using Kontes glass col-
umns (300×48 mm i.d.).
2.01 q (2H, CH2), 2.43 q (2H, CH2), 3.97 q (2H,
CH2O), 5.41 s (1H, CH=). Found, %: C 69.51;
H 10.34. C9H16O2. Calculated, %: C 69.23; H 10.25.
Ethyl 3-methylhex-2-enoate (ΙΙb). Yield 67%,
bp 56–63°C (1–2 mm), nD20 = 1.4420, purity 98%. IR
spectrum, ν, cm–1: 1732 (C=O), 1670 (C=C). 1H NMR
spectrum, δ, ppm: 0.81 t (3H, CH3), 1.23 t (3H, CH3),
1.61 s (3H, CH3), 1.85 m (2H, CH2), 2.07 t (2H, CH2),
3.87 q (2H, CH2O), 5.23 s (1H, CH=). Found, %:
C 69.51; H 10.34. C9H16O2. Calculated, %: C 69.23;
H 10.25.
Ethyl 3-propylhex-2-enoate (ΙΙc). Yield 54%,
bp 78–79°C (1–2 mm), nD20 = 1.4419, purity 94%. IR
spectrum, ν, cm–1: 1730 (C=O), 1670 (C=C). 1H NMR
spectrum, δ, ppm: 0.81 t (6H, CH3), 1.22 t (3H, CH3),
1.87 m (4H, CH2), 2.04 m (4H, CH2), 3.91 q (2H,
CH2O), 5.33 s (1H, CH=). Found, %: C 71.96;
H 10.54. C11H20O2. Calculated, %: C 71.73; H 10.86.
Ethyl 3-ethylhex-2-enoate (ΙΙd). Yield 76%,
bp 59–60°C (1–2 mm), nD20 = 1.4431, purity 97%.
IR spectrum, ν, cm–1: 1735 (C=O), 1671 (C=C).
1H NMR spectrum, δ, ppm: 0.90 t (6H, CH3), 1.27 t
(3H, CH3), 1.57 m (2H, CH2), 1.96 m (2H, CH2),
2.42 m (2H, CH2), 3.93 q (2H, CH2O), 5.42 d (1H,
CH=). Found, %: C 71.83; H 10.24. C10H18O2. Calcu-
lated, %: C 70.58; H 10.58.
Initial ketones I, 2-phenylethanol, 4-phenylbutan-2-
one, ethyl (diethoxyphosphoryl)acetate, triethyl ortho-
acetate, bromotrichloromethane, 2-aminoethanol, po-
tassium tert-butoxide, lithium tetrahydridoaluminate,
copper(I) chloride, and sodium ethoxide were com-
mercial products. Diethyl ether, benzene, tert-butyl
alcohol, hexane, and phenol were purified by standard
procedures [21]. Ethanol was dehydrated according to
the procedure described in [13].
Ethyl 3-methylpent-2-enoate (ΙΙe). Yield 55%,
bp 53–55°C (3–4 mm), nD20 = 1.4421, purity 96%. IR
spectrum, ν, cm–1: 1734 (C=O), 1672 (C=C). 1H NMR
spectrum, δ, ppm: 0.94 t (3H, CH3), 1.14 t (3H, CH3),
1.85 s (3H, CH3), 2.02 m (2H, CH2), 3.95 q (2H,
CH2O), 5.47 s (1H, CH=). Found, %: C 67.81; H 9.45.
C8H14O2. Calculated, %: C 67.60; H 9.85.
Ethyl β,β-substituted acrylates IIa–IIk (general
procedure). Potassium tert-butoxide, 170 mmol, was
added in portions under vigorous stirring to a mixture
of 150 ml of anhydrous benzene, 140 mmol of ethyl
(diethoxyphosphoryl)acetate, and 140 mmol of the cor-
responding ketone I, maintaining the temperature of
the reaction mixture not exceeding 25–30°C. The mix-
ture was stirred for 10–12 h at room temperature and
poured into a beaker containing crushed ice. When the
ice melted, the mixture was transferred into a separa-
tory funnel, the upper organic layer was separated,
washed with distilled water (2×50 ml), and dried over
magnesium sulfate, the solvent was distilled off under
reduced pressure on a rotary evaporator, and the
residue was distilled in a vacuum (1–2 mm). The
concentration of the main substance in the product was
determined by HPLC.
Ethyl cyclopentylideneacetate (ΙΙf). Yield 56%,
bp 200–201°C (760 mm), nD20 = 1.4691, purity 90%. IR
spectrum, ν, cm–1: 1730 (C=O), 1670 (C=C). 1H NMR
spectrum, δ, ppm: 1.10 t (3H, CH3), 1.65 m (4H, CH2),
2.31 t (2H, CH2), 2.63 t (2H, CH2), 4.03 q (2H, CH2O),
5.52 m (1H, CH=). Found, %: C 70.51; H 9.34.
C9H14O2. Calculated, %: C 70.12; H 9.09.
Ethyl cyclohexylideneacetate (ΙΙg). Yield 86%,
bp 92–95°C (3–4 mm), nD20 = 1.4771, purity 98%. IR
spectrum, ν, cm–1: 1735 (C=O), 1670 (C=C). 1H NMR
spectrum, δ, ppm: 1.06 t (3H, CH3), 1.50 m (6H, CH2),
2.27 t (2H, CH2), 2.58 t (2H, CH2), 3.91 q (2H, CH2O),
5.61 m (1H, CH=). Found, %: C 71.85; H 9.74.
C10H16O2. Calculated, %: C 71.42; H 9.52.
Ethyl 3-ethylpent-2-enoate (ΙΙa). Yield 54%,
bp 63–67°C (3–4 mm), nD20 = 1.4423, purity 98%. IR
spectrum, ν, cm–1: 1734 (C=O), 1675 (C=C). 1H NMR
spectrum, δ, ppm: 0.83 t (6H, CH3), 1.10 t (3H, CH3),
Ethyl 3-methyl-4-phenylbut-2-enoate (ΙΙh). Yield
82%, bp 103–105°C (1–2 mm), nD20 = 1.5140, purity
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 8 2008

MIRZABEKOVA et al.
1142
93%. IR spectrum, ν, cm–1: 1734 (C=O), 1675 (C=C).
1H NMR spectrum, δ, ppm: 1.05 t (3H, CH3), 2.01 s
(3H, CH3), 3.15 s (2H, CH2), 3.95 q (2H, CH2O), 5.51 s
(1H, CH=), 7.05 m (5H, C6H5). Found, %: C 76.85;
H 7.54. C13H16O2. Calculated, %: C 76.47; H 7.84.
5.22 m (1H, CH=). Found, %: C 73.24; H 12.34.
C7H14O. Calculated, %: C 73.68; H 12.28.
3-Methylhex-2-en-1-ol (IIΙb). Yield 81%, bp 69–
70°C (1–2 mm), nD20 = 1.4495, purity 94%. IR spec-
trum, ν, cm–1: 3339 (OH), 1665 (C=C). 1H NMR spec-
trum, δ, ppm: 0.96 t (3H, CH3), 1.61 m (2H, CH2),
2.02 s (3H, CH3), 2.37 m (2H, CH2), 3.75 s (1H, OH),
3.97 d (2H, CH2O), 5.37 m (1H, CH=). Found, %:
C 73.88; H 12.52. C7H14O. Calculated, %: C 73.68;
H 12.28.
Ethyl 3-benzylpent-2-enoate (ΙΙi). Yield 65%,
bp 115–117°C (1–2 mm), nD20 = 1.5143, purity 96%. IR
spectrum, ν, cm–1: 1735 (C=O), 1674 (C=C). 1H NMR
spectrum, δ, ppm: 0.84 t (3H, CH3), 1.02 t (3H, CH3),
2.03 q (2H, CH2), 3.12 s (2H, CH2), 3.92 m (2H,
CH2O), 5.51 s (1H, CH=), 7.03 m (5H, C6H5). Found,
%: C 76.35; H 8.52. C14H18O2. Calculated, %: C 77.06;
H 8.25.
3-Propylhex-2-en-1-ol (IIΙc). Yield 81%, bp 68–
69°C (1–2 mm), nD20 = 1.4534, purity 97%. IR spec-
trum, ν, cm–1: 3338 (OH), 1664 (C=C). 1H NMR spec-
trum, δ, ppm: 0.86 m (6H, CH3), 1.51 m (2H, CH2),
1.85 m (2H, CH2), 2.15 m (2H, CH2), 2.31 m (2H,
CH2), 3.21 s (1H, OH), 4.08 d (2H, CH2O), 4.81 d.d
(1H, CH=). Found, %: C 76.46; H 12.32. C9H18O. Cal-
culated, %: C 76.05; H 12.67.
Ethyl 3-methyl-5-phenylpent-2-enoate (ΙΙj).
Yield 76%, bp 114–116°C (1–2 mm), nD20 = 1.5130,
purity 96%. IR spectrum, ν, cm–1: 1734 (C=O), 1672
1
(C=C). H NMR spectrum, δ, ppm: 0.99 t (3H, CH3),
1.82 s (3H, CH3), 2.31 m (4H, CH2), 3.69 q (2H,
CH2O), 5.23 s (1H, CH=), 6.92 s (5H, C6H5). Found,
%: C 76.41; H 8.44. C14H18O2. Calculated, %: C 77.06;
H 8.25.
3-Ethylhex-2-en-1-ol (IIΙd). Yield 85%, bp 62–
63°C (1–2 mm), nD20 = 1.4524, purity 98%. IR spec-
trum, ν, cm–1: 3338 (OH), 1665 (C=C). 1H NMR spec-
trum, δ, ppm: 0.90 t (3H, CH3), 1.04 t (3H, CH3),
1.78 m (2H, CH2), 2.06 m (2H, CH2), 2.25 m (2H,
CH2), 3.58 s (1H, OH), 4.15 d (2H, CH2O), 5.39 m
(1H, CH=). Found, %: C 75.38; H 12.35. C8H16O. Cal-
culated, %: C 75.00; H 12.50.
Ethyl 3-phenylbut-2-enoate (ΙΙk). Yield 63%,
bp 111–112°C (1–2 mm), nD20 = 1.5255, purity 95%. IR
spectrum, ν, cm–1: 1735 (C=O), 1671 (C=C). 1H NMR
spectrum, δ, ppm: 1.27 t (3H, CH3), 2.53 s (3H, CH3),
4.45 q (2H, CH2O), 4.52 t (1H, CH=), 7.15–7.25 m
(5H, C6H5). Found, %: C 76.04; H 7.74. C12H14O2.
Calculated, %: C 75.78; H 7.36.
3-Methylpent-2-en-1-ol (IIΙe). Yield 73%, bp 45–
48°C (1–2 mm), nD20 = 1.4511, purity 94%. IR spec-
trum, ν, cm–1: 3335 (OH), 1662 (C=C). 1H NMR spec-
trum, δ, ppm: 1.05 t (3H, CH3), 2.01 s (3H, CH3),
2.06 m (2H, CH2), 3.39 s (1H, OH), 4.17 d (2H,
CH2O), 5.20 d.d (1H, CH=). Found, %: C 72.35;
H 12.44. C6H12O. Calculated, %: C 72.00; H 12.00.
Substituted alkenols IIIa–IIIk (general proce-
dure). A solution of 50 mmol of ester IIa–IIk in 50 ml
of anhydrous diethyl ether was added under stirring to
a suspension of 30 mmol of LiAlH4 in 50 ml of anhy-
drous diethyl ether; the rate of addition was selected
so that to maintain the mixture weakly boiling. The
mixture was stirred for 4 h at room temperature, cooled
with ice water, and 100 ml of 10% sulfuric acid was
added dropwise to decompose excess reducing agent
(until the precipitate dissolved completely). The prod-
uct was extracted into diethyl ether (3×100 ml), the
combined extracts were dried over magnesium sulfate,
the solvent was distilled off under reduced pressure,
and the residue was subjected to vacuum distillation.
The concentration of the main substance in the product
was determined by HPLC.
2-(Cyclopentylidene)ethanol (IIΙh). Yield 76%,
bp 66–67°C (1–2 mm), nD20 = 1.4873, purity 96%. IR
1
spectrum, ν, cm–1: 3320 (OH), 1650 (C=C). H NMR
spectrum, δ, ppm: 1.47 m (4H, CH2), 2.31 m (4H,
CH2), 3.31 s (1H, OH), 4.11 d (2H, CH2O), 5.42 d.d
(1H, CH=). Found, %: C 75.25; H 10.44. C7H12O.
Calculated, %: C 75.00; H 10.71.
2-(Cyclohexylidene)ethanol (IIΙg). Yield 78%,
bp 80–84°C (1–2 mm), nD20 = 1.4936, purity 90%. IR
1
spectrum, ν, cm–1: 3325 (OH), 1650 (C=C). H NMR
3-Ethylpent-2-en-1-ol (IIΙa). Yield 76%, bp 55–
56°C (1–2 mm), nD20 = 1.4516, purity 99%. IR spec-
trum, ν, cm–1: 3335 (OH), 1665 (C=C). 1H NMR spec-
trum, δ, ppm: 0.85 m (6H, CH3), 1.93 q (2H, CH2),
2.06 q (2H, CH2), 3.48 s (1H, OH), 4.13 d (2H, CH2O),
spectrum, δ, ppm: 1.48 m (2H, CH2), 1.53 m (4H,
CH2), 2.17 m (2H, CH2), 2.48 m (2H, CH2), 3.40 s
(1H, OH), 3.92 d (2H, CH2O), 5.36 d.d (1H, CH=).
Found, %: C 76.38; H 11.47. C8H14O. Calculated, %:
C 76.19; H 11.11.
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SYNTHESIS AND BIOLOGICAL ACTIVITY OF PERMETHRINIC ACID ANALOGS
1143
3-Methyl-4-phenylbut-2-en-1-ol (IIΙh). Yield
93%, bp 104–106°C (1–2 mm), nD20 = 1.5470, purity
87%. IR spectrum, ν, cm–1: 3340 (OH), 1665 (C=C).
1H NMR spectrum, δ, ppm: 1.55 s (3H, CH3), 3.18 s
(2H, CH2), 4.12 d (2H, CH2O), 4.31 s (1H, OH), 5.45 t
(1H, CH=), 7.05 m (5H, C6H5). Found, %: C 81.22;
H 8.49. C11H14O. Calculated, %: C 81.48; H 8.64.
The concentration of the main substance in the product
was determined by HPLC.
b. A mixture of 85 mmol of compound IIIa–IIIk,
170 mmol of triethyl orthoacetate, and 0.8 mmol of
phosphoric acid was heated for 2 h at 120°C under
stirring with simultaneous removal of ethanol liberated
during the reaction. When ethanol was no longer dis-
tilled off, the temperature of the mixture was raised to
150°C, and the mixture was heated for 8 h at that tem-
perature (TLC) and distilled under reduced pressure to
isolate unreacted triethyl orthoacetate and ester IVa–
IVl. The concentration of the main substance in the
product was determined by HPLC.
3-Benzylpent-2-en-1-ol (IIΙi). Yield 93%, bp 113–
115°C (1–2 mm), nD20 = 1.5270, purity 92%. IR spec-
trum, ν, cm–1: 3341 (OH), 1662 (C=C). 1H NMR spec-
trum, δ, ppm: 1.01 t (3H, CH3), 2.12 m (2H, CH2),
3.21 m (2H, CH2), 3.96 d (2H, CH2O), 4.20 s (1H,
OH), 6.10 d.d (1H, CH=), 7.05 m (5H, C6H5). Found,
%: C 81.47; H 9.36. C12H16O. Calculated, %: C 81.81;
H 9.09.
Ethyl 3,3-diethylpent-4-enoate (IVa). Yield 70%,
bp 78–80°C (1–2 mm), nD20 = 1.4364, purity 94%. IR
1
spectrum: ν 1645 cm–1 (C=C). H NMR spectrum, δ,
3-Methyl-5-phenylpent-2-en-1-ol (IIΙj). Yield
95%, bp 120–122°C (1–2 mm), nD20 = 1.5344, purity
90%. IR spectrum, ν, cm–1: 3340 (OH), 1665 (C=C).
1H NMR spectrum, δ, ppm: 1.92 s (3H, CH3), 2.03 m
(2H, CH2), 2.91 m (2H, CH2), 4.50 s (1H, OH), 4.11 d
(2H, CH2O ), 5.90 t (1H, CH=), 6.72 m (5H, C6H5).
Found, %: C 81.57; H 8.56. C10H12O. Calculated, %:
C 81.08; H 8.10.
ppm: 0.69 t (6H, CH3), 0.98 m (2H, CH2), 1.11 t (3H,
CH3), 1.23 m (2H, CH2), 2.08 s (2H, CH2), 4.06 q
(2H, CH2O), 4.27 m (2H, =CH2), 5.57 m (1H, CH=).
Found, %: C 72.04; H 11.14. C11H20O2. Calculated, %:
C 71.73; H 10.86.
Ethyl 3-methyl-3-propylpent-4-enoate (IVb).
Yield 63%, bp 78–81°C (1–2 mm), nD20 = 1.4435, purity
92%. IR spectrum: ν 1644 cm–1 (C=C). 1H NMR spec-
trum, δ, ppm: 0.81 t (3H, CH3), 0.91 m (2H, CH2),
1.06 s (3H, CH3), 1.11 t (3H, CH3), 1.21 m (1H, CH2),
1.39 m (1H, CH2), 2.09 d (1H, CH2), 2.21 d (1H, CH2),
4.13 q (2H, CH2O), 4.62 m (2H, =CH2), 5.48 m (1H,
CH=). Found, %: C 72.12; H 11.07. C11H20O2. Calcu-
lated, %: C 71.73; H 10.86.
3-Phenylbut-2-en-1-ol (IIΙk). Yield 90%, bp 101–
103°C (1–2 mm), nD20 = 1.5267, purity 93%. IR spec-
trum, ν, cm–1: 3342 (OH), 1664 (C=C). 1H NMR spec-
trum, δ, ppm: 1.53 s (3H, CH3), 3.98 s (2H, CH2O),
4.10 s (1H, OH), 5.47 t (1H, CH=), 7.07 m (5H, C6H5).
Found, %: C 81.58; H 9.39. C12H16O. Calculated, %:
C 81.81; H 9.09.
Ethyl pent-4-enoates IVa–IVl (general proce-
dures). a. A mixture of 50 mmol of alkenol IIIa–IIIk,
60 mmol of triethyl orthoacetate, and 0.75 mmol of
phenol was stirred for 9–10 h on heating at 135–140°C
with simultaneous removal of ethanol liberated during
the process. When ethanol was no longer distilled off
(~0.05 mol), the mixture was heated for 3–5 h at 140–
150°C, cooled, and dissolved in 100 ml of diethyl
ether, and the solution was stirred, the formation of
compounds IV being monitored by TLC. When the
Claisen rearrangement was complete, the mixture was
cooled to room temperature, treated with 1 N hydro-
chloric acid (2×50 ml) to decompose unreacted tri-
ethyl orthoacetate, and washed with a saturated solu-
tion of sodium hydrogen carbonate (2×50 ml) and
water (2×50 ml). The ether layer was separated, dried
over magnesium sulfate, and evaporated on a rotary
evaporator under reduced pressure. The residue was
subjected to either vacuum distillation or chromato-
graphic separation in a column charged with silica gel.
Ethyl 3,3-dipropylpent-4-enoate (IVc). Yield
77%, bp 63–65°C (4–5 mm), nD20 = 1.4312, purity 94%.
1
IR spectrum: ν 1642 cm–1 (C=C). H NMR spectrum,
δ, ppm: 0.77 d.t (6H, CH3), 0.83 m (4H, CH2), 1.25 t
(3H, CH3), 1.26 m (2H, CH2), 1.46 m (2H, CH2),
2.21 s (2H, CH2), 4.15 q (2H, CH2O), 4.77 m (2H,
=CH2), 5.63 m (1H, CH=). Found, %: C 73.94;
H 11.46. C13H24O2. Calculated, %: C 73.58; H 11.32.
Ethyl 3-ethyl-3-propylpent-4-enoate (IVd). Yield
59%, bp 82–84°C (1–2 mm), nD20 = 1.4410, purity 95%.
1
IR spectrum: ν 1645 cm–1 (C=C). H NMR spectrum,
δ, ppm: 0.78 m (6H, CH3), 0.86 m (2H, CH2), 1.11 m
(2H, CH2), 1.21 t (3H, CH3), 1.46 m (2H, CH2), 2.11 d
(1H, CH2), 2.19 d (1H, CH2), 4.13 q (2H, CH2O),
5.02 m (2H, =CH2), 5.72 m (1H, CH=). Found, %:
C 72.99; H 11.53. C12H22O2. Calculated, %: C 72.72;
H 11.11.
Ethyl 3-ethyl-3-methylpent-4-enoate (IVe). Yield
60%, bp 82–84°C (1–2 mm), nD20 = 1.4410, purity 95%.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 8 2008

MIRZABEKOVA et al.
1144
1
IR spectrum: ν 1644 cm–1 (C=C). H NMR spectrum,
δ, ppm: 0.77 t (3H, CH3), 1.06 s (3H, CH3), 1.14 m
(1H, CH2), 1.23 t (3H, CH3), 1.33 m (1H, CH2), 2.15 d
(1H, CH2), 2.23 d (1H, CH2), 4.09 q (2H, CH2O),
5.08 m (2H, =CH2), 5.86 m (1H, CH=). Found, %:
C 70.27; H 10.35. C10H18O2. Calculated, %: C 70.58;
H 10.58.
C 78.43; H 9.37. C16H22O2. Calculated, %: C 78.04;
H 8.94.
Ethyl 3-methyl-3-phenylpent-4-enoate (IVk).
Yield 60%, bp 71–73°C (1–2 mm), nD20 = 1.4626, purity
89%. IR spectrum: ν 1641 cm–1 (C=C). 1H NMR spec-
trum, δ, ppm: 1.07 t (3H, CH3), 1.48 s (3H, CH3),
2.12 d (1H, CH2), 2.32 d (1H, CH2), 3.91 q (2H,
CH2O), 5.05 m (2H, =CH2), 6.02 d.d (1H, CH=),
7.28 m (5H, C6H5). Found, %: C 77.54; H 8.59.
C14H18O2. Calculated, %: C 77.06; H 8.25.
Ethyl (1-vinylcyclopentyl)acetate (IVf). Yield
72%, bp 87–90°C (1–2 mm), nD20 = 1.4292, purity 92%.
1
IR spectrum: ν 1645 cm–1 (C=C). H NMR spectrum,
δ, ppm: 1.09 t (3H, CH3), 1.62 m (2H, CH2), 1.67 m
(2H, CH2), 1.69 m (2H, CH2), 1.91 m (2H, CH2),
2.12 s (2H, CH2), 3.87 q (2H, CH2O), 4.99 d.d (2H,
=CH2), 5.63 t (1H, CH=). Found, %: C 72.38; H 9.55.
C11H18O2. Calculated, %: C 72.52; H 9.89.
Ethyl 3-phenylpent-4-enoate (IVl). Yield 52%,
bp 102–104°C (1–2 mm), nD20 = 1.4853, purity 93%. IR
1
spectrum: ν 1639 cm–1 (C=C). H NMR spectrum, δ,
ppm: 1.21 t (3H, CH3), 2.51 m (1H, CH2), 2.71 m (1H,
CH2), 3.67 m (1H, CH), 3.97 q (2H, CH2O), 4.97 m
(2H, =CH2), 5.95 m (1H, CH=), 7.3 m (5H, C6H5).
Found, %: C 77.25; H 8.24. C13H16O2. Calculated, %:
C 76.47; H 7.84.
Ethyl (1-vinylcyclohexyl)acetate (IVg). Yield
76%, bp 66–69°C (1–2 mm), nD20 = 1.4525, purity 87%.
1
IR spectrum: ν 1645 cm–1 (C=C). H NMR spectrum,
Ethyl 4-bromo-6,6,6-trichlorohexanoates Va–Vl
(general procedure). A mixture of 130 mmol of
bromotrichloromethane, 43 mmol of ethyl pentenoate
IVa–IVl, 45 mmol of 2-aminoethanol, 1 mmol of
copper(I) chloride, and 310 mmol of tert-butyl alcohol
was heated to the boiling point (84–85°C) and was
maintained boiling under stirring for 6 h. The progress
of the reaction was monitored by GLC (sample were
withdrawn from the mixture in 2 h and then every 1 h
until the reaction was complete). Excess tert-butyl
alcohol and bromotrichloromethane were removed
under reduced pressure on a rotary evaporator, and the
residue was purified by preparative column chroma-
tography on silica gel. The purity of the products was
determined by HPLC.
δ, ppm: 1.11 t (3H, CH3), 1.41 m (6H, CH2), 1.45 m
(2H, CH2), 1.50 m (2H, CH2), 3.95 q (2H, CH2O),
5.01 m (2H, =CH2), 5.63 d.d (1H, CH=). Found, %:
C 73.27; H 9.86. C12H20O2. Calculated, %: C 73.46;
H 10.20.
Ethyl 3-benzyl-3-methylpent-4-enoate (IVh).
Yield 85%, bp 104–106°C (1–2 mm), nD20 = 1.4956,
purity 95%. IR spectrum: ν 1639 cm–1 (C=C). 1H NMR
spectrum, δ, ppm: 1.11 t (3H, CH3), 1.19 s (3H, CH3),
2.16 d (1H, CH2), 2.36 d (1H, CH2), 2.47 d (1H, CH2),
2.87 d (1H, CH2), 4.04 q (2H, CH2O), 5.00 m (2H,
=CH2), 5.69 m (1H, CH=), 7.08 m (5H, C6H5). Found,
%: C 77.72; H 8.91. C15H20O2. Calculated, %: C 77.58;
H 8.62.
Ethyl 3-benzyl-3-ethylpent-4-enoate (IVi). Yield
82%, bp 90–93°C (1–2 mm), nD20 = 1.4950, purity 93%.
Ethyl 4-bromo-6,6,6-trichloro-3,3-diethylhexan-
oate (Va). Yield 73% (51% after chromatographic
1
IR spectrum: ν 1640 cm–1 (C=C). H NMR spectrum,
1
purification), purity 98%. H NMR spectrum, δ, ppm:
δ, ppm: 0.82 t (3H, CH3), 1.06 m (2H, CH2), 1.11 t
(3H, CH3), 2.0 m (1H, CH2), 2.02 d (1H, CH2), 2.56 d
(1H, CH2), 2.80 d (1H, CH2), 4.08 q (2H, CH2), 4.97 m
(2H, CH2=), 5.71 m (1H, =CH), 6.98 d (2H, C6H5),
7.15 m (3H, C6H5). Found, %: C 78.34; H 9.25.
C16H22O2. Calculated, %: C 78.04; H 8.94.
0.83 t (6H, CH3), 1.23 t (3H, CH3), 1.28 m (2H, CH2),
1.53 m (2H, CH2), 2.37 s (2H, CH2), 3.26 m and
3.36 m (1H each, 5-H), 4.07 q (2H, CH2O), 4.21 d
(1H, CHBr). Found, %: C 37.41; H 4.94; Br 21.03;
Cl 27.98. C12H20BrCl3O2. Calculated, %: C 37.68;
H 5.27; Br 20.89; Cl 27.80.
Ethyl 3-methyl-3-(2-phenylethyl)pent-4-enoate
Ethyl 4-bromo-6,6,6-trichloro-3-methyl-3-pro-
(IVj). Yield 78%, bp 125–127°C (1–2 mm), nD20
=
pylhexanoate (Vb). Yield 78% (62% after chromato-
1
1.4943, purity 95%. IR spectrum: ν 1640 cm–1 (C=C).
1H NMR spectrum, δ, ppm: 1.25 s (3H, CH3), 1.30 t
(3H, CH3), 1.63 m (1H, CH2), 1.83 m (1H, CH2),
2.12 d (1H, CH2), 2.38 d (1H, CH2), 2.61 m (2H,
CH2CH2), 4.15 q (2H, CH2O), 5.10 m (2H, =CH2),
5.96 m (1H, CH=), 7.35 m (5H, C6H5). Found, %:
graphic purification), purity 97%. H NMR spectrum,
δ, ppm: 0.86 t (3H, CH3), 1.14 s (3H, CH3), 1.24 t (3H,
CH3), 1.32 m (2H, CH2), 1.44 m (1H, CH2), 1.54 m
(1H, CH2), 2.44 d (1H, CH2), 2.58 d (1H, CH2),
3.04 d.d and 3.19 d (1H each, 5-H), 4.12 q (2H,
CH2O), 4.35 m (1H, CHBr). Found, %: C 37.34;
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SYNTHESIS AND BIOLOGICAL ACTIVITY OF PERMETHRINIC ACID ANALOGS
1145
H 5.11; Br 21.17; Cl 28.10. C12H20BrCl3O2. Calculat-
ed, %: C 37.68; H 5.27; Br 20.89; Cl 27.80.
Ethyl 3-benzyl-4-bromo-6,6,6-trichloro-3-meth-
ylhexanoate (Vh). Yield 75% (52% after chromato-
1
graphic purification), purity 98%. H NMR spectrum,
Ethyl 4-bromo-6,6,6-trichloro-3,3-dipropylhex-
δ, ppm: 1.21 t (3H, CH3), 1.32 s (3H, CH3), 2.49 d
(1H, CH2), 2.64 d (1H, CH2), 2.79 d (1H, CH2), 2.98 d
(1H, CH2), 3.09 d and 3.25 m (1H each, 5-H), 4.01 q
(2H, CH2O), 4.27 m (1H, CHBr), 7.18 m (5H, C6H5).
Found, %: C 44.37; H 4.31; Br 18.72; Cl 24.95.
C16H20BrCl3O2. Calculated, %: C 44.59; H 4.64;
Br 18.58; Cl 24.73.
anoate (Vc). Yield 69% (49% after chromatographic
purification), purity 98%. H NMR spectrum, δ, ppm:
1
0.75 t (6H, CH3), 1.02 t (3H, CH3), 1.10 m (2H, CH2),
1.15 m (2H, CH2), 1.25 m (2H, CH2), 1.38 m (2H,
CH2), 2.26 s (2H, CH2), 3.12 d.d and 3.25 d (1H each,
5-H), 3.92 q (2H, CH2O), 4.28 d (1H, CHBr). Found,
%: C 40.75; H 5.68; Br 19.74; Cl 26.07. C14H24BrCl3O2.
Calculated, %: C 40.92; H 5.84; Br 19.48; Cl 25.94.
Ethyl 3-benzyl-4-bromo-6,6,6-trichloro-3-ethyl-
hexanoate (Vi). Yield 63% (47% after chromato-
Ethyl 4-bromo-6,6,6-trichloro-3-ethyl-3-propyl-
1
graphic purification), purity 97%. H NMR spectrum,
hexanoate (Vd). Yield 73% (58% after chromato-
δ, ppm: 0.95 t (3H, CH3), 1.18 t (3H, CH3), 1.26 m
(1H, CH2), 1.43 m (1H, CH2), 2.17 m (2H, CH2),
2.68 m (2H, CH2), 3.15 d and 3.65 d.d (1H each, 5-H),
4.10 q (2H, CH2O), 4.68 m (1H, CHBr), 7.42 m (5H,
C6H5). Found, %: C 45.62; H 5.07; Br 18.23; Cl 24.16.
C17H22BrCl3O2. Calculated, %: C 45.89; H 4.94;
Br 17.99; Cl 23.95.
1
graphic purification), purity 98%. H NMR spectrum,
δ, ppm: 0.90 t (6H, CH3), 1.21 m (1H, CH2), 1.26 t
(3H, CH3), 1.30 m (1H, CH2), 1.48 m (1H, CH2),
1.52 m (1H, CH2), 2.38 d (1H, CH2), 2.51 d (1H, CH2),
3.16 d and 3.29 m (1H each, 5-H), 4.02 q (2H, CH2O),
4.57 m (1H, CHBr). Found, %: C 40.54; H 5.62;
Br 19.63; Cl 26.21. C12H22BrCl3O2. Calculated, %:
C 39.34; H 5.54; Br 20.17; Cl 26.86.
Ethyl 4-bromo-6,6,6-trichloro-3-methyl-3-(2-
phenylethyl)hexanoate (Vj). Yield 68% (48% after
1
Ethyl 4-bromo-6,6,6-trichloro-3-ethyl-3-methyl-
chromatographic purification), purity 96%. H NMR
hexanoate (Ve). Yield 81% (57% after chromato-
spectrum, δ, ppm: 1.19 m (6H, CH3), 1.54 m (1H,
CH2), 1.81 m (1H, CH2), 2.38 d (1H, CH2), 2.51 d (1H,
CH2), 2.59 d.d (2H, CH2), 3.09 d and 3.22 m (1H each,
5-H), 4.05 m (2H, CH2O), 4.53 m (1H, CHBr), 7.12 m
(5H, C6H5). Found, %: C 45.57; H 5.12; Br 18.14;
Cl 24.22. C17H22BrCl3O2. Calculated, %: C 45.89;
H 4.94; Br 17.99; Cl 23.95.
1
graphic purification), purity 96%. H NMR spectrum,
δ, ppm: 0.95 t (3H, CH3), 1.13 s (3H, CH3), 1.26 t (3H,
CH3), 1.37 m (1H, CH2), 1.61 m (1H, CH2), 2.37 d
(1H, CH2), 2.48 d (1H, CH2), 3.19 d and 3.32 m (1H
each, 5-H), 4.07 q (2H, CH2O), 4.48 m (1H, CHBr).
Found, %: C 35.64; H 4.71; Br 21.98; Cl 29.12.
C11H18BrCl3O2. Calculated, %: C 35.82; H 4.88;
Br 21.70; Cl 28.90.
Ethyl 4-bromo-6,6,6-trichloro-3-methyl-3-phen-
ylhexanoate (Vk). Yield 65% (49% after chromato-
1
Ethyl 2-[1-(1-bromo-2,2,2-trichloroethyl)cyclo-
graphic purification), purity 93%. H NMR spectrum,
pentyl]acetate (Vf). Yield 77% (55% after chromato-
graphic purification), purity 98%. H NMR spectrum,
δ, ppm: 0.97 t (3H, CH3), 1.68 s (3H, CH3), 2.63 d
(1H, CH2), 2.78 d (1H, CH2), 3.18 d and 3.31 m (1H
each, 5-H), 4.16 q (2H, CH2O), 4.75 m (1H, CHBr),
7.29 m (5H, C6H5). Found, %: C 43.13; H 4.12;
Br 19.39; Cl 25.73. C15H18BrCl3O2. Calculated, %:
C 43.21; H 4.32; Br 19.20; Cl 25.57.
1
δ, ppm: 1.27 t (3H, CH3), 1.46 m (2H, CH2), 1.55 m
(2H, CH2), 1.68 m (4H, CH2), 2.47 s (2H, CH2), 3.26 d
and 3.39 d.d (1H each, 5-H), 4.08 q (2H, CH2O),
4.51 m (1H, CHBr). Found, %: C 37.52; H 4.51;
Br 21.22; Cl 28.31. C12H18BrCl3O2. Calculated, %:
C 37.84; H 4.73; Br 21.02; Cl 27.98.
Ethyl 4-bromo-6,6,6-trichloro-3-phenylhexano-
ate (Vl). Yield 73% (52% after chromatographic
1
purification), purity 94%. H NMR spectrum, δ, ppm:
Ethyl 2-[1-(1-bromo-2,2,2-trichloroethyl)cyclo-
1.12 t (3H, CH3), 2.72 m (2H, CH2), 3.15 m and
3.32 m (1H each, 5-H), 3.72 m (1H, CH), 4.04 m (2H,
CH2O), 4.82 m (1H, CHBr), 7.38 m (5H, C6H5).
Found, %: C 41.54; H 3.76; Br 20.06; Cl 26.64.
C14H16BrCl3O2. Calculated, %: C 41.73; H 3.97;
Br 19.87; Cl 26.45.
hexyl]acetate (Vg). Yield 78% (64% after chromato-
graphic purification), purity 97%. H NMR spectrum,
1
δ, ppm: 1.07 t (3H, CH3), 1.49 m (6H, CH2), 1.58 m
(2H, CH2), 1.65 m (2H, CH2), 2.43 s (2H, CH2),
3.13 m and 3.26 m (1H each, 5-H), 3.85 q (2H, CH2O),
4.58 m (1H, CHBr). Found, %: C 39.41; H 4.87;
Br 20.43; Cl 27.21. C13H20BrCl3O2. Calculated, %:
C 39.54; H 5.06; Br 20.27; Cl 26.99.
Ethyl cyclopropanecarboxylates VIa–VIk (gen-
eral procedure). A solution of 110 mmol of sodium
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MIRZABEKOVA et al.
1146
ethoxide prepared from 2.53 g of metallic sodium and
100 ml of anhydrous ethanol was added to a solution
of 50 mmol of ester Va–Vl in 200 ml of anhydrous
ethanol, cooled to 0°C. The mixture was slowly (over
a period of 1 h) allowed to warm up to room tempera-
ture under stirring and was then heated for 1 h under
reflux (the solution turned colorless, and a solid sepa-
rated). The mixture was evaporated to a volume of
30 ml, 100 g of ice was added, and the mixture was
neutralized with ice-cold 1 N hydrochloric acid and
extracted with diethyl ether (2×100 ml). The ether
extract was washed with a saturated solution of sodium
hydrogen carbonate (2 × 50 ml) and a solution of
sodium chloride (2 ×50 ml) and dried over sodium
sulfate. The solvent was distilled off under reduced
pressure on a rotary evaporator, and the residue was
subjected to column chromatography on silica gel. The
products were light yellow oily substances (yield 45–
55% after chromatographic purification). Their purity
was determined by HPLC.
3-H), 4.03 q (2H, OCH2), 6.24 d (1H, CH=); c-Me-t-
Pr-t-CHCCl2: 0.89 t (3H, CH3), 1.10 s (3H, CH3),
1 22 t (3H, OCH2CH3), 1.35 m (2H, CH2), 1.47 m (1H,
CH2), 1.48 d (1H, 1-H), 1.49 m (1H, CH2), 2.06 t (1H,
3-H), 3.99 q (2H, OCH2), 5.49 d (1H, CH=); t-Me-t-
Pr-c-CHCCl2: 0.92 t (3H, CH3), 1.02 s (3H, CH3),
1.15 t (3H, CH3), 1.17 m (1H, CH2), 1.22 m (1H, CH2),
1.30 m (2H, CH2), 1.48 d (1H, 1-H), 2.10 t (1H, 3-H),
4.02 q (2H, OCH2), 5.47 d (1H, CH=). 13C NMR spec-
trum, δC, ppm: c-Me-t-Pr-c-CHCCl2: 12.2, 13.6, 14.3,
19.7, 28.7, 31.3, 31.8, 44.4, 60.3, 120.3, 125.0, 170.8;
t-Me-c-Pr-c-CHCCl2: 13.9, 14.4, 19.7, 25.7, 28.5, 29.9,
30.2, 31.8, 60.1, 120.4, 125.0, 170.0; c-Me-t-Pr-t-
CHCCl2: 14.0, 14.3, 17.1, 19.6, 32.7, 32.9, 34.8, 35.4,
60.6, 121.7, 127.1, 170.9; t-Me-t-Pr-c-CHCCl2: 13.6,
14.2, 19.8, 19.8, 32.4, 32.7, 34.6, 38.7, 60.4, 121.8,
128.3, 171.2. Mass spectrum, m/z: 263 [M]+. Found,
%: C 54.51; H 7.08; Cl 27.77. C12H18Cl2O2. Calculat-
ed, %: C 54.33; H 6.79; Cl 26.79. M 263.20.
Ethyl 3-(2,2-dichlorovinyl)-2,2-dipropylcyclo-
propane-1-carboxylate (VIc). Yield 63% (52% after
chromatographic purification), purity 95%. IR spec-
Ethyl 3-(2,2-dichlorovinyl)-2,2-diethylcyclopro-
pane-1-carboxylate (VIa). Yield 73% (47% after
chromatographic purification), purity 96%. IR spec-
1
trum: ν 1619 cm–1 (C=C). H NMR spectrum, δ, ppm:
1
trum: ν 1619 cm–1 (C=C). H NMR spectrum, δ, ppm:
cis isomer: 0.72 t (3H, CH3 ), 0.75 t (3H, CH3), 1.02 m
(1H, CH2), 1.07 t (3H, CH3), 1.25 m (1H, CH2), 1.27 m
(2H, CH2), 1.37 m (1H, CH2), 1.42 m (1H, CH2), 1.48 t
(2H, CH2), 1.62 d (1H, 1-H), 1.84 t (1H, 3-H), 3.95 q
(2H, OCH2), 6.23 d (1H, CH=); trans isomer: 0.70 t
(3H, CH3), 0.73 t (3H, CH3), 1.14 m (3H, CH3), 1.16 m
(1H, CH2), 1.19 m (1H, CH2), 1.21 m (1H, CH2),
1.24 m (1H, CH2), 1.28 m (1H, CH2), 1.35 m (1H,
CH2), 1.39 m (1H, CH2), 1.43 d (1H, 1-H), 2.03 d.d
(1H, 3-H), 3.95 q (2H, OCH2), 5.44 d (1H, CH=).
13C NMR spectrum, δ, ppm: cis isomer: 14.0, 14.1,
14.2, 19.2, 19.3, 27.0, 31.1, 32.0, 35.1, 40.5, 60.2,
120.1, 124.9, 170.5; trans isomer: 13.9, 14.0, 14.2,
19.3, 19.5, 31.3, 32.2, 34.5, 34.9, 36.72, 60.5, 121.3,
127.1, 170.8. Mass spectrum: m/z 293 [M]+. Found, %:
C 57.62; H 7.32; Cl 24.67. C14H22Cl2O2. Calculated,
%: C 57.33; H 7.50; Cl 24.23. M 293.26.
cis isomer: 0.71 t (3H, CH3 ), 0.79 t (3H, CH3), 1.10 t
(3H, CH3), 1.12 m (1H, CH2), 1.40 m (1H, CH2),
1.54 m (2H, CH2), 1.64 d (1H, 1-H), 1.86 t (1H, 3-H),
3.97 q (2H, OCH2), 6.24 d (1H, CH=); trans isomer:
0.68 t (3H, CH3), 0.76 t (3H, CH3), 1.07 t (3H, CH3),
1.14 m (1H, CH2), 1.35 m (1H, CH2), 1.37 m (1H,
CH2), 1.43 d (1H, 1-H), 1.52 m (1H, CH2), 2.03 d.d
(1H, 3-H), 3.95 q (2H, OCH2), 5.45 d (1H, CH=).
13C NMR spectrum, δC, ppm: cis isomer: 10.2, 10.3,
10.4, 17.1, 30.5, 31.3, 31.9, 37.4, 60.3, 120.2, 124.8,
170.5; trans isomer: 10.3, 10.5, 14.2, 21.6, 25.1, 32.5,
34.5, 39.0, 60.5, 121.4, 127.1, 170.9. Mass spectrum:
m/z 265 [M]+. Found, %: C 54.44; H 7.17; Cl 27.84.
C12H18Cl2O2. Calculated, %: C 54.33; H 6.79;
Cl 26.79. M 265.21.
Ethyl 3-(2,2-dichlorovinyl)-2-methyl-2-propyl-
cyclopropane-1-carboxylate (VIb). Yield 64% (49%
after chromatographic purification), purity 94%. IR
Ethyl 3-(2,2-dichlorovinyl)-2-ethyl-2-propyl-
cyclopropane-1-carboxylate (VId). Yield 63% (54%
after chromatographic purification), purity 94%. IR
1
spectrum: ν 1619 cm–1 (C=C). H NMR spectrum, δ,
1
spectrum: ν 1619 cm–1 (C=C). H NMR spectrum, δ,
ppm: c-Me-t-Pr-c-CHCCl2: 0.80 t (3H, CH3), 1.09 s
(3H, CH3), 1.14 t (3H, CH3), 1.34 m (2H, CH2), 1.40 m
(1H, CH2), 1.42 m (1H, CH2), 1.70 d (1H, 1-H), 1.89 t
(1H, 3-H), 4.09 q (2H, OCH2), 6.19 d (1H, CH=);
t-Me-c-Pr-c-CHCCl2: 0.85 t (3H, CH3), 1.07 s (3H,
CH3), 1.18 t (3H, CH3), 1.25 m (1H, CH2), 1.28 m (1H,
CH2), 1.36 m (2H, CH2), 1.73 d (1H, 1-H), 1.92 t (1H,
ppm: c-Et-t-Pr-c-CHCCl2: 0.80 t (3H, CH3), 0 82 t
(3H, CH3), 1.14 t (3H, CH3), 1.26 m (2H, CH2), 1.28 m
(2H, CH2), 1.39 m (2H, SH2), 1.73 d (1H, 1-H), 1.99 t
(1H, 3-H), 4.01 q (2H, OCH2), 6.18 d (1H, CH=).
13C NMR spectrum, δC, ppm: 10.8, 13.9, 14.1, 19.4,
29.9, 31.6, 31.9, 34.9, 43.8, 60.1, 121.2, 124.8, 172.1.
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SYNTHESIS AND BIOLOGICAL ACTIVITY OF PERMETHRINIC ACID ANALOGS
1147
Mass spectrum: m/z 279 [M]+. Found, %: C 56.21;
H 7.38; Cl 25.77. C13H20Cl2O2. Calculated, %: C 55.91;
H 7.16; Cl 25.44. M 279.23.
Ethyl 2-benzyl-3-(2,2-dichlorovinyl)-2-methyl-
cyclopropane-1-carboxylate (VIh). Yield 63% (51%
after chromatographic purification), purity 96%. IR
1
spectrum: ν 1620 cm–1 (C=C). H NMR spectrum, δ,
Ethyl 3-(2,2-dichlorovinyl)-2-ethyl-2-methyl-
cyclopropane-1-carboxylate (VIe). Yield 70% (52%
after chromatographic purification), purity 96%. IR
ppm: c-Me-t-Bzl-c-CHCCl2: 1.13 s (3H, CH3), 1.18
t (3H, CH3), 1.93 d (1H, 1-H), 2.15 t (1H, 3-H), 2.61 d
(1H, CH2Ph), 2.71 d (1H, CH2Ph), 4.05 q (2H, OCH2),
6.29 d (1H, CH=), 7.10–7.24 m (5H, Ph); t-Me-c-Bzl-
c-CHCCl2: 1.04 s (3H, CH3), 1.15 t (3H, CH3), 1.89 d
(1H, 1-H), 2.08 t (1H, 3-H), 2.9 d (1H, CH2Ph), 3.08 d
(1H, CH2Ph), 4.05 q (2H, OCH2), 6.49 d (1H, CH=),
7.09–7.23 m (5H, Ph); c-Me-t-Bzl-t-CHCCl2: 1.08 s
(3H, CH3), 1.18 t (3H, CH3), 1.85 d (1H, 1-H), 2.27 t
(1H, 3-H), 2.60 d (1H, CH2Ph), 2.67 d (1H, CH2Ph),
4.07 q (2H, OCH2), 5.69 d (1H, CH=), 7.12–7.26 m
(5H, Ph); t-Me-c-Bzl-t-CHCCl2: 1.00 s (3H, CH3),
1.18 t (3H, CH3), 1.66 d (1H, 1-H), 2.48 t (1H, 3-H),
2.84 d (1H, CH2Ph), 2.95 d (1H, CH2Ph), 4.07 q
(2H, OCH2), 5.53 d (1H, CH=), 7.12–7.26 m (5H, Ph).
13C NMR spectrum, δC, ppm: c-Me-t-Bzl-c-CHCCl2:
13.0, 14.2, 30.2, 30.7, 31.6, 47.1, 60.6, 120.8, 124.8,
126.7–137.8, 170.9; t-Me-c-Bzl-c-CHCCl2: 14.4, 25.7,
29.1, 31.8, 32.8, 34.0, 60.4, 121.0, 124.9, 126.5–137.9,
171.0; c-Me-t-Bzl-t-CHCCl2: 14.4, 17.4, 32.2, 32.8,
34.5, 42.0, 60.9, 122.2, 126.5–138.5, 126.6, 171.2;
t-Me-c-Bzl-t-CHCCl2: 14.5, 19.9, 32.4, 33.4, 34.7,
38.9, 60.7, 122.3, 126.5–138.5, 126.9, 171.1. Mass
spectrum: m/z 313 [M]+. Found, %: C 61.55; H 6.09;
Cl 22.99. C16H18Cl2O2. Calculated, %: C 61.34; H 5.75;
Cl 22.68. M 313.24.
1
spectrum: ν 1619 cm–1 (C=C). H NMR spectrum, δ,
ppm: c-Me-t-Et-c-CHCCl2: 0.82 t (3H, CH3), 1.04 s
(3H, CH3), 1.12 t (3H, CH3), 1.24 m (2H, CH2), 1.65 d
(1H, 1-H), 1.87 t (1H, 3-H), 4.09 q (2H, OCH2), 6.20 d
(1H, CH=); t-Me-c-Et-c-CHCCl2: 0.82 t (3H, CH3),
1.04 s (3H, CH3), 1.18 t (3H, CH3), 1.73 d (1H, 1-H),
1.92 t (1H, 3-H), 4.03 q (2H, OCH2), 6.24 d (1H,
CH=); c-Me-t-Et-t-CHCCl2: 0.80 t (3H, CH3), 1.05 s
(3H, CH3), 1.07 t (3H, CH3), 1.17 m (1H, CH2), 1.28 m
(1H, CH2), 1.42 d (1H, 1-H), 2.04 m (1H, 3-H), 3.95 q
(2H, OCH2), 5.44 d (1H, CH=). 13C NMR spectrum,
δC, ppm: c-Me-t-Et-c-CHCCl2: 10.4, 11.7, 14.3, 30.6,
32.2, 32.9, 35.5, 60.3, 120.3, 124.9, 171.2; t-Me-c-Et-
c-CHCCl2: 10.5, 14.2, 24.9, 31.1, 31.6, 32.4, 35.1,
60.2, 120.2, 125.0, 170.4; c-Me-t-Et-t-CHCCl2: 10.6,
14.3, 16.4, 29.5, 32.9, 33.6, 34.4, 60.5, 121.5, 127.09,
170.8. Mass spectrum: m/z 251 [M]+. Found, %:
C 52.90; H 6.64; Cl 28.56. C11H16Cl2O2. Calculated,
%: C 52.58; H 6.37; Cl 28.28. M 251.17.
Ethyl 2-(2,2-dichlorovinyl)spiro[2.4]heptane-1-
carboxylate (VIf). Yield 58% (44% after chromato-
graphic purification), purity 95%. IR spectrum:
1
ν 1615 cm–1 (C=C). H NMR spectrum, δ, ppm: 1.27 t
(3H, CH3), 1.56 d (1H, 1-H), 1.69 m (4H, CH2), 1.73 d
(2H, CH2), 1.79 t (2H, CH2), 2.38 d.d (1H, 2-H),
4.15 q (2H, OCH2), 5.52 d (1H, CH=). 13C NMR spec-
trum, δC, ppm: 14.3, 25.5, 26.2, 29.9, 32.1, 33.1, 34.1,
36.2, 60.4, 121.4, 126.9, 170.3. Mass spectrum:
m/z 263 [M]+. Found, %: C 54.46; H 5.82; Cl 27.38.
C12H16Cl2O2. Calculated, %: C 54.75; H 6.08; Cl 26.99.
M 263.13.
Ethyl 2-benzyl-3-(2,2-dichlorovinyl)-2-ethyl-
cyclopropane-1-carboxylate (VIi). Yield 59% (45%
after chromatographic purification), purity 95%. IR
1
spectrum: ν 1620 cm–1 (C=C). H NMR spectrum, δ,
ppm: c-Et-t-Bzl-c-CHCCl2: 0.85 t (3H, CH3), 1.18 t
(3H, CH3), 1.44 m (1H, CH2), 1.50 m (1H, CH2),
1.83 d (1H, 1-H), 2.12 t (1H, 3-H), 2.60 d (1H,
CH2Ph), 2.77 d (1H, CH2Ph), 4.02 q (2H, OCH2),
6.33 d (1H, CH=), 7.09–7.25 m (5H, Ph); c-Bzl-t-Et-c-
CHCCl2: 0.83 t (3H, CH3), 1.07 m (1H, CH2), 1.18 t
(3H, CH3), 1.38 m (1H, CH2), 1.85 d (1H, 1-H), 2.06 t
(1H, 3-H), 2.92 d (1H, CH2Ph), 3.05 d (1H, CH2Ph),
4.05 q (2H, OCH2), 6.45 d (1H, CH=), 7.02–7.20 m
(5H, Ph); c-Et-t-Bzl-t-CHCCl2: 0.82 t (3H, CH3),
1.14 t (3H, CH3), 1.35 m and 1.42 m (1H each, CH2),
1.80 d (1H, 1-H), 2.25 t (1H, 3-H), 2.66 m (1H,
CH2Ph), 2.68 m (1H, CH2Ph), 4.08 q (2H, OCH2),
5.65 d (1H, CH=), 7.09–7.23 m (5H, Ph); c-Bzl-t-Et-t-
CHCCl2: 0.83 t (3H, CH3), 1.18 t (3H, CH3), 1.20 m
(1H, CH2), 1.25 m (1H, CH2), 1.68 d (1H, 1-H),
Ethyl 2-(2,2-dichlorovinyl)spiro[2.5]octane-1-
carboxylate (VIg). Yield 57% (44% after chromato-
graphic purification), purity 96%. IR spectrum:
1
ν 1615 cm–1 (C=C). H NMR spectrum, δ, ppm: 1.07 t
(3H, CH3), 1.36 m (2H, 6-H), 1.47 m (1H, 4-H or
8-H), 1.48 m (2H, 5-H or 7-H), 1.53 m (2H, 5-H or
7-H), 1,59 m (1H, 8-H or 4-H), 1.61 m (1H, 4-H or
8-H), 1.63 m (1H, 8-H or 4-H), 1.69 m (1H, 1-H),
2.24 d.d (1H, 2-H), 4.11 q (2H, OCH2), 5.59 d (1H,
CH=). 13C NMR spectrum, δC, ppm: 14.32, 25.4, 25.5,
26.0, 29.9, 32.5, 32.6, 33.0, 36.9, 60.4, 121.9, 126.5,
170.4. Mass spectrum: m/z 277 [M]+. Found, %:
C 56.08; H 6.15; Cl 24.67. C13H18Cl2O2. Calculated,
%: C 56.31; H 6.49; Cl 25.63. M 277.21.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 8 2008

MIRZABEKOVA et al.
1148
CHCCl2: 14.4, 22.0, 32.7, 34.3, 38.5, 60.9, 120.9–
138.9, 124.1, 126.9, 170.8. Mass spectrum: m/z 229
[M]+. Found, %: C 60.57; H 5.82; Cl 23.36.
C15H16Cl2O2. Calculated, %: C 60.20; H 5.35; Cl 23.74.
M 299.21.
2.49 m (1H, 3-H), 2.90 d (1H, CH2Ph), 2.98 d (1H,
CH2Ph), 4.07 q (2H, OCH2), 5.57 d (1H, CH=), 7.10–
7.26 m (5H, Ph). 13C NMR spectrum, δC, ppm: c-Et-t-
Bzl-c-CHCCl2: 10.3, 14.3, 18.5, 29.7, 31.0, 36.6, 42.6,
60.5, 120.5, 120.6–138.9, 124.6, 170.5; c-Bzl-t-Et-c-
CHCCl2: 10.4, 14.3, 30.3, 31.0, 31.3, 31.6, 36.7,
60.6, 120.6, 120.8–138.7, 124.9, 171.5; c-Et-t-Bzl-t-
CHCCl2: 10.8, 14.4, 22.4, 31.7, 34.7, 37.9, 38.4, 60.8,
118.6–138.1, 122.4, 126.3, 170.7; c-Bzl-t-Et-t-
CHCCl2: 10.6, 14.4, 25.5, 32.7, 34.3, 34.5, 60.7, 122.3,
123.5–138.5, 126.9, 171.1. Mass spectrum: m/z 327
[M]+. Found, %: C 62.64; H 6.37; Cl 22.12.
C17H20Cl2O2. Calculated, %: C 62.38; H 6.11; Cl 21.71.
M 327.27.
Assessment of acaricidal activity. Experiments
were performed under laboratory conditions on stand-
ard sensitive laboratory strains of typhoid fly Musca
domestica L., rice weevils Calandra oryzae L., bean
aphides Aphys fabae Stock., and twospotted spider
mite Tetranychus urticae Koch. Tests for juvenile
hormone activity were performed on chrysalises of
flour beetle Tenebrio molitor L. The acute phyto-
toxicity was studied on hydrangea or cucumber leaves.
All experiments were carried out in triplicate.
Ethyl 3-(2,2-dichlorovinyl)-2-methyl-2-(2-phen-
ylethyl)cyclopropane-1-carboxylate (VIj). Yield 53%
(45% after chromatographic purification), purity 95%.
This study was performed under financial support
by the International Scientific and Technical Center
(project no. 2480.2003).
1
IR spectrum: ν 1621 cm–1 (C=C). H NMR spectrum,
δ, ppm: c-Me-t-(CH2)2Ph-c-CHCCl2: 1.21 t (3H,
CH2CH3), 1.33 s (3H, CH3), 1.59 d (1H, 1-H), 1.78 m
and 1.80 m (1H each, CH2), 2.24 t (1H, 3-H), 2.68 m
(1H, CH2Ph), 2.78 m (1H, CH2Ph), 4.10 q (2H, OCH2),
5.58 d (1H, CH=), 7.11–7.25 m (5H, Ph). 13C NMR
spectrum, δC, ppm: c-Me-t-(CH2)2Ph-c-CHCCl2: 14.4,
17.2, 32.5, 32.9, 33.0, 34.6, 60.8, 122.0, 126.0–141.9,
127.0, 170.8. Mass spectrum: m/z 327 [M]+. Found, %:
C 62.44; H 6.32; Cl 21.97. C17H20Cl2O2. Calculated,
%: C 62.38; H 6.11; Cl 21.71. M 327.27.
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spectrum: ν 1621 cm–1 (C=C). H NMR spectrum, δ,
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OCH2), 5.65 d (1H, CH=), 7.09–7.23 m (5H, Ph);
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CH3), 1.68 d (1H, 1-H), 2.48 t (1H, 3-H), 4.08 q (2H,
OCH2), 5.56 d (1H, CH=), 7.10–7.23 m (5H, Ph).
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124.6, 170.5; t-Me-c-Ph-c-CHCCl2: 14.3, 23.54, 31.3,
31.6, 36.7, 60.6, 120.8–138.7, 122.3, 124.8, 171.5;
c-Me-t-Ph-t-CHCCl2: 14.4, 21.4, 31.7, 34.7, 38.4,
60.8, 118.6–138.1, 121.6, 126.3, 170.7; t-Me-c-Ph-t-
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