Synthesis of aryl-containing isoprenoids from 1,5-dimethylcycloocta-1,5- diene

Article abstract of DOI:10.1134/S1070428010060059

A procedure has been developed for the synthesis of Pro-Drone homo analogs from the ozonolysis products of 1,5-dimethylcycloocta-1,5-diene and 1,5-dimethylcyclooctene.

Full text of DOI:10.1134/S1070428010060059

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 6, pp. 798–806. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © O.S. Kukovinets, A.G. Kukovinets, V.G. Kasradze, E.V. Salimova, M.I. Abdullin, 2010, published in Zhurnal Organicheskoi Khimii,
2010, Vol. 46, No. 6, pp. 808–815.
Synthesis of Aryl-Containing Isoprenoids
from 1,5-Dimethylcycloocta-1,5-diene
O. S. Kukovinetsa, A. G. Kukovinetsa, V. G. Kasradzeb, E. V. Salimovab, and M. I. Abdullina
a Bashkir State University, Ufa, Bashkortostan, Russia
b Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences,
pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia
e-mail: salimovaev@mail.ru
Received June 25, 2009
Abstract—A procedure has been developed for the synthesis of Pro-Drone homo analogs from the ozonolysis
products of 1,5-dimethylcycloocta-1,5-diene and 1,5-dimethylcyclooctene.
DOI: 10.1134/S1070428010060059
The most important methods for the protection of
warm-blooded animals and agricultural products from
deleterious effects, including those produced by causa-
tive organisms and insect vectors, are based on integral
approaches with the use of hormones controlling
behavioral response (pheromones) and insecticides
[1], growth and development regulators (juvenoids)
and drugs [2], etc. Here, each component should be
nontoxic and species-specific. Pro-Drone (I) and its
nor and homo analogs are among means ensuring suc-
cessful control over various dipteran pests at poultry
and fur farms [3].
derived from bromide VIII gave 2,6-dimethyl-10-(4-
isopropylphenyl)dec-1-ene (IX). In the H NMR spec-
1
trum of IX we observed two doublets at δ 1.09 and
1.28 ppm and a singlet at δ 1.70 ppm with an intensity
ratio of 1:2:1 from the methyl groups, multiplets from
methylene and methine protons (δ 1.45–1.56 ppm),
and an unresolved signal at δ 7.20 ppm from aromatic
protons. Introduction of a methoxy group into mole-
cule IX according to the procedure described in [5]
afforded target 1-(4-isopropylphenyl)-9-methoxy-5,9-
dimethyldecane (I) (Scheme 1). The IR spectrum of I
lacked absorption bands assignable to terminal double
1
bond, and its H and 13C NMR spectra contained sig-
Retrosynthetic analysis has shown that a convenient
synthon for compound I is keto acetal III obtained
previously from 1,5-dimethylcycloocta-1,5-diene (II)
[4]. By Wittig olefination of the oxo group in III with
methylidene(triphenyl)phosphorane and subsequent
removal of the dimethyl acetal protection we obtained
4,8-dimethylnon-8-enal (V) which displayed in the
IR spectrum absorption bands at 940, 1640, 3080
(terminal methylene group) and 1725 cm–1 (CHO); the
1H NMR spectrum of V contained a broadened singlet
at δ 9.6 ppm.
nals typical of a methoxy group (δ 3.03, δC 52.40 ppm)
together with signals belonging to aromatic ring. These
data confirmed the formation of homo-Pro-Drone (I)
whose overall yield was 8%, calculated on the initial
compound III. We succeeded in raising the yield of I
to 21% following an alternative procedure for the
replacement of the hydroxy group in alcohol VI by
bromine (using CBr4/PPh3).
Compound XIV was synthesized via olefination of
the oxo group in III with ethylidene(triphenyl)phos-
phorane and subsequent transformations which were
analogous to those described above for the synthesis of
compound I (Scheme 2).
Unsaturated aldehyde V was then used to synthe-
size Pro-Drone (I) homo analog. For this purpose, the
aldehyde group in V was reduced to hydroxymethyl
with sodium tetrahydridoborate, and alcohol VI thus
formed was converted into bromide VIII through in-
termediate p-toluenesulfonate VII. Alkylation of p-iso-
propylbenzyl chloride with the Grignard compound
Pro-Drone homo analogs XV and XVI having
a double bond at the 4- or 5-position of the isoprenoid
chain were synthesized from 9,9-dimethoxy-6-methyl-
non-5-en-2-one (XVII); the latter was obtained by
798

SYNTHESIS OF ARYL-CONTAINING ISOPRENOIDS
799
Scheme 1.
O
Me
Me
Me
Me
Ph3P=CH2
96%
OMe
OMe
OMe
OMe
Me
H2C
Me
II
III
IV
Me
Me
Me
Me
H+/H2O
94%
NaBH4
98%
OH
H2C
CHO
H2C
V
VI
Me
Me
TsCl, pyridine
61%
OTs
H2C
VII
58% LiBr, Me2CO
Me
Me
Me
(1) Mg, Et2O
(2) 4-ClCH2C6H4Pr-i
Me
CBr4, PPh3
92%
H2C
Br
H2C
Pr-i
VIII
IX
Me
Me
(1) Hg(OAc)2, MeOH
(2) NaBH4, NaOH, H2O
Me
MeO
62%
Pr-i
I
partial ozonolysis of 1,5-dimethylcycloocta-1,5-diene
(II) [4]. Olefination of XVII with ethylidene- or meth-
ylidene(triphenyl)phosphorane, removal of the di-
methyl acetal protection, reduction of the aldehyde
group, and treatment of alcohols XXII and XXIII with
p-toluenesulfonyl chloride in the presence of pyridine
gave 4,8-dimethylnona-4,8-dien-1-yl p-toluenesulfo-
nate (XXIV) or 4,8-dimethyldeca-4,8-dien-1-yl p-tolu-
enesulfonate (XXV), respectively. By alkylation of
XXIV and XXV with the Grignard compound derived
from p-isopropylbenzylmagnesium chloride we ob-
tained homo analogs XV and XVI (Scheme 3). Com-
pounds XV and XVI can be obtained in higher yields
when alcohols XXII and XXIII were preliminarily
Scheme 2.
(1) H+/H2O
(2) NaBH4
Me
Me
Me
Me
MeCH=PPh3
OMe
OMe
OH
Me
Me
III
X
XI
Me
Me
Me
Me
(1) TsCl, pyridine
(2) LiBr, Me2CO
or CBr4, PPh3
(1) Mg, Et2O
(2) 4-ClCH2C6H4Pr-i
Br
Me
Me
82 or 92%
48%
Pr-i
XII
XIII
Me
Me
Me
(1) Hg(OAc)2, MeOH
(2) NaBH4, NaOH
MeO
62%
Pr-i
XIV
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 6 2010

KUKOVINETS et al.
800
Scheme 3.
Me
Me
(1) O3, cyclohexane, MeOH
(2) Me2S
(3) MeOH, NH4Cl
MeO
MeO
R
Ph3P=CHR
O
II
84%
85–87%
OMe
OMe
Me
Me
Me
XVII
XVIII, XIX
Me
Me
TsCl
pyridine
O
R
HO
R
TsO
R
H+/H2O
LiAlH4
88–90%*
Me
Me
Me
XX, XXI
XXII, XXIII
XXIV, XXV
Me
Me
R
Me
MgCl
Me
48–52%
Me
Me
XV, XVI
XV, XVIII, XX, XXII, XXIV, R = H; XVI, XIX, XXI, XXIII, XXV, R = Me.
converted into bromides XXVI and XXVII and
Grignard compounds derived from the latter were sub-
jected to coupling with more reactive p-isopropyl-
benzyl chloride (Scheme 4).
measured on a Bruker AM-300 spectrometer at 300
and 75.46 MHz, respectively using CDCl3 as solvent;
the chemical shifts are given relative to tetramethyl-
silane. GLC analysis was performed on a Chrom-5
chromatograph; 1200×3-mm column, stationary phase
5% of SE-30 on Chromaton N-AW-DMCS (grain
size 0.16–0.20 mm); oven temperature 50–300°C;
carrier gas helium.
An alternative route to p-toluenesulfonates XXIV
and XXV is based on ozonolysis of 1,5-dimethyl-
cycloocta-1,5-diene (II) to obtain keto acid XXVIII
which is then converted into methyl ester XXIX. The
subsequent Wittig olefination of the oxo group with
methylidene- or ethylidene(triphenyl)phosphorane,
reduction of esters XXX and XXXI with lithium
tetrahydridoaluminate, and treatment of alcohols XXII
and XXIII with p-toluenesulfonyl chloride in pyridine
gave p-toluenesulfonates XXIV and XXV in an overall
yield of 57–62% (Scheme 5).
1-(4-Isopropylphenyl)-9-methoxy-5,9-dimethyl-
decane (I). Compound IX, 0.6 g (2.1 mmol), was
dissolved in 9 ml of anhydrous methanol, the solution
was cooled to 5°C, and 0.80 g Hg(OAc)2 was added
under argon. The mixture was stirred for 1 h, allowed
to warm up to 20°C, kept for 24 h, and cooled to 0°C,
and a mixture of 0.33 g NaBH4, 0.92 g of sodium
hydroxide, and 1.13 ml of water was added dropwise
under stirring. The mixture was kept for 1 h at 0°C and
for 2 h at 20°C, poured into water, and extracted with
ethyl acetate. The extract was washed with a saturated
solution of sodium chloride, dried over MgSO4, and
filtered, the solvent was distilled off, and the residue
EXPERIMENTAL
The IR spectra in the range from 400 to 4000 cm–1
were recorded from thin films on a Specord M-80
1
spectrometer. The H and 13C NMR spectra were
Scheme 4.
Me
(1) Mg, Et2O
R
Br
CBr4, PPh3
94%
(2) 4-ClCH2C6H4Pr-i
XXII, XXIII
XV, XVI
72%
Me
XXVI, XXVII
XV, XXII, XXVI, R = H; XVI, XXIII, XXVII, R = Me.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 6 2010

SYNTHESIS OF ARYL-CONTAINING ISOPRENOIDS
801
Scheme 5.
(1) O3, cyclohexane, AcOH
(2) AcONa, AcOH
(3) H2O
Me
Me
Me
Me
H+, MeOH
98%
O
O
II
93%
O
O
OH
OMe
XXVIII
XXIX
Me
Me
O
Ph3P=CHR
75–77%
LiAlH4
R
R
95–98%
Me
Me
OMe
OH
XXX, XXXI
XXII, XXIII
Me
TsCl, pyridine
90–98%
R
Me
OTs
XXIV, XXV
XXII, XXIV, XXX, R = H; XXIII, XXV, XXXI, R = Me.
chromatography on silica gel using hexane as eluent.
was purified by chromatography on silica gel using
petroleum ether–ethyl acetate (9:1) as eluent. Yield
0.41 g (62%). Light yellow oily substance. IR spec-
trum, ν, cm–1: 3080 w, 1600 m, 1105 s, 1005 s.
1H NMR spectrum, δ, ppm: 1.06 d (3H, 5-CH3, J =
6.0 Hz), 1.23 s and 1.25 s (3H each, 9-CH3, C10H3),
1.28 d [6H, (CH3)2CH, J = 6.0 Hz], 1.40–1.56 m (13H,
CH2, CH), 2.32 m [3H, C1H2, (CH3)2CH], 3.03 s (3H,
OCH3), 7.20 br.s (4H, Harom). 13C NMR spectrum, δC,
ppm: 18.34 q (5-CH3), 20.98 t (C7), 23.45 q (CH3CH),
28.03 t (C3), 30.53 q (C10, 9-CH3), 31.18 t (C2), 31.24 d
(C5), 33.70 d (C6H4CH), 35.61 t (C1), 36.84 t (C6),
37.33 t (C4), 44.08 t (C8), 51.14 q (OCH3), 60.84 s
(C9), 127.50 and 127.67 d (Co, Cm), 141.13 s (Ci),
148.94 s (Cp). Found, %: C 82.64; H 12.46. C22H38O.
Calculated, %: C 83.02; H 11.95.
Yield 3.8 g (96%). IR spectrum, ν, cm–1: 1640 m,
1
1135 s, 1080 s, 1020 m, 910 m. H NMR spectrum, δ,
ppm: 0.89 d (3H, CH3, J = 7.0 Hz), 1.25–1.50 m (7H,
CH, CH2), 1.60 m (2H, 8-H), 1.68 s (3H, 2-CH3),
2.26 t (2H, 3-H, J = 6.5 Hz), 3.15 s (6H, OCH3), 4.25 t
(1H, 9-H, J = 5.5 Hz), 4.80 br.s (2H, 1-H). Found, %:
C 72.61; H 12.45. C13H26O2. Calculated, %: C 72.90;
H 12.15.
4,8-Dimethylnon-8-en-1-ol (VI). Acetal IV, 2.74 g
(12.8 mmol), was dissolved in 100 ml of purified
acetone, 2.74 ml of water and 0.74 g of pyridinium
p-toluenesulfonate were added, and the mixture was
heated for 2 h under reflux. The solvent was distilled
off, the residue was dissolved in ethyl acetate, and the
solution was washed in succession with saturated solu-
tions of NaHCO3 and NaCl, dried over MgSO4,
filtered, and evaporated to obtain 2.02 g (94%) of al-
dehyde V (IR spectrum, ν, cm–1: 3050 w, 2750 m,
1725 s, 1645 s, 1180 s, 1120 m, 900 m). The latter
(without additional purification) was dissolved in
25 ml of anhydrous methanol, 0.74 g of sodium tetra-
hydridoborate was added in portions, and the resulting
suspension was stirred for 1 h and left to stand for
12 h. The mixture was treated under stirring with
12 ml of a 5% solution of acetic acid in water and
stirred for 30 min, methanol was distilled off under
reduced pressure, the residue was extracted with ethyl
acetate, the extract was dried over MgSO4 and
filtered, and the solvent was distilled off to obtain
2.09 g of a viscous oily substance which was purified
by chromatography on silica gel using petroleum
ether–ethyl acetate (3:1) as eluent. Yield 2.0 g (98%).
9,9-Dimethoxy-6-methylnonan-2-one (III) was
synthesized as described in [4].
2,6-Dimethyl-9,9-dimethoxynon-1-ene (IV).
A suspension of 7.29 g (20 mmol) of methyl(triphenyl)-
phosphonium bromide in 40 ml of anhydrous tetra-
hydrofuran was cooled to –70°C, and 10.6 ml of
a 3.3 M solution of n-butyllithium in hexane diluted
with 10 ml of anhydrous THF was added dropwise
under argon, maintaining the temperature at –60 to
–70°C. The mixture was stirred until it became bright
red (ylide formation, ~1 h) and allowed to slowly
warm up to –30°C, 4 g (18.5 mmol) of keto acetal III
was added, and the mixture was stirred for 1 h at
–30°C and left to stand for 12 h at 20°C. The mixture
was then diluted with 150 ml of hexane, stirred, and
filtered through a small layer of silica gel, the solvent
was distilled off, and the residue was subjected to
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 6 2010

KUKOVINETS et al.
802
IR spectrum, ν, cm–1: 3200–3560 br.s, 3030 w, 1645 m,
905 m. 1H NMR spectrum, δ, ppm: 0.98 d (3H, 4-CH3,
J = 6.0 Hz), 1.52–1.59 m (9H, CH, CH2), 1.72 s (3H,
8-CH3), 2.21 t (2H, 7-H, J = 7.5 Hz), 3.82 t (2H, 1-H,
J = 7.0 Hz), 4.93 br.s (2H, 9-H), 5.04 br.s (1H, OH).
Found, %: C 77.38; H 13.02. C11H22O. Calculated, %:
C 77.65; H 12.94.
0.63 g (92%). Samples of VIII obtained by the two
methods (a and b) were identical.
10-(p-Isopropylphenyl)-2,6-dimethyldec-1-ene
(IX). A solution of Grignard compound prepared from
1.5 g (6.4 mmol) of bromide VIII and 0.15 g of
magnesium in 20 ml of anhydrous THF was heated to
the boiling point, a solution of 1.34 g (8.0 mmol) of
p-isopropylbenzyl chloride in 15 ml of anhydrous THF
was added dropwise, and the mixture was heated under
reflux until compound VIII disappeared completely
(TLC, silica gel, eluent hexane). The mixture was
cooled, washed with a saturated solution of sodium
chloride, and dried over MgSO4, the drying agent was
filtered off, the solvent was distilled off, and the
residue was subjected to chromatography on silica gel
using hexane as eluent. Yield 0.77 g (42%), light
yellow oily substance. IR spectrum, ν, cm–1: 3080 w,
9-Bromo-2,6-dimethylnon-1-ene (VIII). a. Alco-
hol VI, 2.0 g (11.8 mmol), was dissolved in 26 ml of
anhydrous pyridine, the solution was cooled to 0°C,
2.3 g of p-toluenesulfonyl chloride was added under
stirring, and the mixture was stirred for 3 h at 0°C and
left to stand for 12 h at 5°C. The mixture was then
poured into 40 g of an ice–water mixture and extracted
with methylene chloride. The extract was washed in
succession with 1 N hydrochloric acid and saturated
solutions of NaHCO3 and NaCl, dried over MgSO4,
and evaporated. The residue was 2.10 g (61%) of
p-toluenesulfonate VII; IR spectrum, ν, cm–1: 3080 w,
1645 m, 1600 m, 1505 m, 900 m. Lithium bromide,
0.9 g (10.3 mmol), was dispersed in 60 ml of anhy-
drous acetone, 2.80 g (9.6 mmol) of compound VII
was added under stirring in an argon atmosphere, and
the mixture was stirred until compound VII disap-
peared completely (TLC; petroleum ether–ethyl
acetate, 6:3). The solvent was distilled off, the residue
was diluted with diethyl ether, the resulting solution
was washed in succession with saturated solutions of
NaHCO3 and NaCl and dried over MgSO4, the solvent
was distilled off, and the residue was subjected to
chromatography on silica gel using petroleum ether–
ethyl acetate (19:1) as eluent. Yield 1.14 g (58%),
yellow viscous oily liquid. IR spectrum, ν, cm–1:
1
1660 m, 1600 w, 1510 m, 910 m. H NMR spectrum,
δ, ppm: 1.09 d (3H, 6-CH3, J = 6.0 Hz), 1.28 d [6H,
(CH3)2CH, J = 6.0 Hz], 1.45–1.56 m (11H, CH2, CH),
1.70 s (3H, 2-CH3), 2.03 br.s (2H, 3-H), 2.28 and
2.36 m [10-H, (CH3)2CH], 4.85 br.s (2H, 1-H), 7.20 m
(4H, Harom). Found, %: C 88.27; H 11.91. C21H34. Cal-
culated, %: C 88.11; H 11.89.
10,10-Dimethoxy-3,7-dimethyldec-2-ene (X).
A solution of 2.7 g (12.5 mmol) of acetal III in 20 ml
of anhydrous THF was added to a solution of phos-
phorus ylide prepared from 5.2 g (14 mmol) of ethyl-
(triphenyl)phosphonium bromide and 17 ml of a 1.4 M
solution of n-BuLi in hexane at –70°C under argon in
45 ml of THF, as described above in the synthesis of
compound IV. When the reaction was complete, the
product was isolated in a similar way. Yield 2.02 g
(71%), light yellow oily liquid. IR spectrum, ν, cm–1:
1
3030 w, 1655 m, 1030 m, 905 m, 690 m. H NMR
1
spectrum, δ, ppm: 0.98 d (3H, 6-CH3, J = 6.5 Hz),
1.45–1.60 m (9H, CH2, CH), 1.72 s (3H, 2-CH3), 1.90 t
(2H, 3-H, J = 7.0 Hz), 3.37 t (2H, CH2Br, J = 7.0 Hz),
4.87 br.s (2H, 1-H). Found, %: C 56.31; H 9.23;
Br 34.44. C11H21Br. Calculated, %: C 56.65; H 9.01;
Br 34.33.
1650 w, 1135 s, 1070 s, 1060 s, 890 m. H NMR
spectrum, δ, ppm: 0.89 d (3H, 7-H, J = 7.0 Hz), 1.40–
1.55 m (9H, CH, CH2), 1.68 d (3H, 1-H, J = 6.5 Hz),
1.72 s (3H, 3-CH3), 2.03 t (2H, 4-H, J = 6.5 Hz), 3.18 s
(6H, OCH3), 4.25 t (1H, 10-H, J = 5.5 Hz), 5.06 q (1H,
2-H, J = 7.0 Hz). Found, %: C 73.84; H 12.18.
C14H28O2. Calculated, %: C 73.68; H 12.28.
b. Carbon tetrabromide, 1.35 g (4.06 mmol), was
added at 20°C to a solution of 0.5 g (2.9 mmol) of
alcohol VI and 1.02 g (3.90 mmol) of triphenyl-
phosphine in 5 ml of anhydrous methylene chloride.
The mixture was stirred for 2 h at 20°C, 30 ml of ethyl
acetate was added, and the mixture was washed in
succession with saturated solutions of NaHCO3 and
NaCl and dried over MgSO4. The solvent was distilled
off, the residue was diluted with hexane, the precipitate
was filtered off, and the filtrate was evaporated. Yield
4,8-Dimethyldec-8-en-1-ol (XI). Following the
procedure described above for the synthesis of com-
pound V, treatment of 2 g (8.8 mmol) of acetal X with
2 ml of water and 0.70 g of pyridinium p-toluene-
sulfonate in 90 ml of anhydrous acetone gave the
corresponding aldehyde which (without additional
purification) was reduced with 0.70 g of NaBH4 in
22 ml of anhydrous methanol. The mixture was treated
with 8.2 ml of a 5% solution of acetic acid in water as
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 6 2010

SYNTHESIS OF ARYL-CONTAINING ISOPRENOIDS
803
described above for the synthesis of VI. Yield 1.29 g
(80%), light yellow oily liquid. IR spectrum, ν, cm–1:
3400 br.s, 1645 m, 905 m. The product was used in
the synthesis of bromide XII without additional
purification.
Samples of XII obtained by the two methods (a and b)
were identical in spectral parameters.
11-(p-Isopropylphenyl)-3,7-dimethylundec-2-ene
(XIII) was synthesized as described above for com-
pound IX by heating a mixture of 1.68 g (10.0 mmol)
of p-isopropylbenzyl chloride and Grignard compound
prepared from 2.0 g (8.1 mmol) of bromide XII and
0.19 g of magnesium. The product was isolated by
column chromatography on silica gel using hexane as
eluent. Yield 1.17 g (48%). IR spectrum, ν, cm–1:
3080 w, 1655 m, 1600 w, 980 m. 1H NMR spectrum, δ,
ppm: 0.88 d (3H, 7-CH3, J = 6.0 Hz), 1.21 d [6H,
(CH3)2CH, J = 6.0 Hz], 1.40–1.50 m (11H, CH2, CH),
1.62 d (3H, 1-H, J = 6.5 Hz), 1.69 s (3H, 3-CH3),
1.95 t (2H, 4-H, J = 6.5 Hz), 2.35 t (2H, 11-H, J =
6.5 Hz), 2.41 m [1H, (CH3)2CH], 7.20–7.35 br.s (4H,
Harom). Found, %: C 88.08; H 12.06. C22H36. Calculat-
ed, %: C 88.00; H 12.00.
10-Bromo-3,7-dimethyldec-2-ene (XII). a. A solu-
tion of 0.24 g (1.3 mmol) of alcohol XI in 3 ml of
anhydrous pyridine was cooled to 0°C, 0.27 g of
p-toluenesulfonyl chloride was added, and the mixture
was stirred for 2 h at 0°C and left to stand for 8 h at
5°C. The mixture was poured into an ice–water mix-
ture, and the product was extracted into diethyl ether.
The extracts were combined, washed in succession
with 1 N hydrochloric acid and saturated solutions of
NaCl, NaHCO3, and NaCl again, dried over MgSO4,
filtered, and evaporated. The residue was 0.42 g of
4,8-dimethyldec-8-en-1-yl p-toluenesulfonate which
was added while stirring under argon to a suspension
of 0.12 g of lithium bromide in 15 ml of anhydrous
acetone. The mixture was stirred until 4,8-dimethyl-
dec-8-en-1-yl p-toluenesulfonate disappeared (TLC,
silica gel, petroleum ether–diethyl ether, 1:1), the
solvent was distilled off, the residue was diluted with
diethyl ether, and the resulting solution was washed in
succession with saturated solutions of Na2S2O3 and
NaCl and dried over MgSO4. The drying agent was
filtered off, and the solvent was distilled off under
reduced pressure to isolate 0.31 g of crude bromide
XII which was purified by column chromatography on
silica gel using petroleum ether as eluent. Yield 0.26 g
(82%, calculated on alcohol XI), light yellow oily sub-
stance. IR spectrum, ν, cm–1: 1640 m, 780 m, 690 m.
1H NMR spectrum, δ, ppm: 0.93 d (3H, 7-CH3, J =
6.5 Hz), 1.40–1.56 m (9H, CH, CH2), 1.62 d (3H, 1-H,
J = 7.0 Hz), 1.68 s (3H, 3-CH3), 2.28 t (2H, 4-H, J =
7.0 Hz), 3.19 t (2H, CH2Br, J = 7.5 Hz), 5.12 q (1H,
2-H, J = 7.0 Hz). Found, %: C 58.43; H 9.18; Br 32.68.
C12H23Br. Calculated, %: C 58.30; H 9.31; Br 32.39.
1-(p-Isopropylphenyl)-9-methoxy-5,9-dimethyl-
undecane (XIV) was synthesized as described above
for compound I by treatment of 0.6 g (2 mmol) of
compound XIII with 0.45 g of mercury(II) acetate,
followed by reduction of intermediate organomercury
compound with 0.33 g of NaBH4 in alkaline medium.
The product was purified by chromatography on silica
gel using petroleum ether–ethyl acetate (9:1) as eluent.
Yield 0.41 g (62%), light yellow viscous oily sub-
stance. IR spectrum, ν, cm–1: 2950 br.s, 1600 w,
1
1505 m, 1105 s. H NMR spectrum, δ, ppm: 0.89 t
(3H, C11H3, J = 6.5 Hz), 1.04 d (3H, 5-CH3, J =
7.0 Hz), 1.22 d [6H, (CH3)2CH, J = 6.0 Hz], 1.28 s
(3H, 9-CH3), 1.40–1.52 m (15H, CH, CH2), 2.43 m
[3H, (CH3)2CH, 1-H], 3.16 s (3H, OCH3), 7.20–7.40 m
(4H, Harom). Found, %: C 88.04; H 11.81. C23H40O.
Calculated, %: C 88.13; H 12.05.
10-(p-Isopropylphenyl)-2,6-dimethyldeca-1,5-di-
ene (XV). a. A solution of Grignard compound pre-
pared from 6 g (35.6 mmol) of p-isopropylbenzyl
chloride and 1 g (41.7 mmol) of magnesium in 30 ml
of anhydrous diethyl ether was cooled to –30°C,
a solution of 2 g (6.2 mmol) of p-toluenesulfonate
XXIV in 12 ml of anhydrous THF was added drop-
wise, the mixture was cooled to –70°C, 3.1 ml of
a 0.1 M solution of Li2CuCl4 in anhydrous THF was
added dropwise, and the mixture was kept for 1.5 h at
–70°C, allowed to slowly warm up to 20°C, and left to
stand for 12 h at 20°C. The mixture was then cooled to
5–10°C, 100 ml of 10% hydrochloric acid was added,
and the mixture was extracted with methylene chlo-
ride. The extract was dried over MgSO4 and filtered,
b. Carbon tetrabromide, 0.48 g (1.4 mmol), was
added at room temperature to a solution of 0.24 g
(1.3 mmol) of alcohol XI and 0.35 g (1.3 mmol) of
triphenylphosphine in 2 ml of methylene chloride, and
the mixture was stirred for 2 h at room temperature and
diluted with ethyl acetate. The organic solution was
washed in succession with saturated solutions of
NaHCO3 and NaCl, dried over MgSO4, filtered, and
evaporated, the residue was diluted with hexane, and
the precipitate was filtered off. The filtrate was evap-
orated, and the residue was purified by chromatog-
raphy as described above in a. Yield 0.30 g (92%).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 6 2010

KUKOVINETS et al.
804
the solvent was distilled off, and the residue was sub-
jected to chromatography on silica gel using hexane as
eluent. Yield 0.92 g (52%), yellow oily liquid. IR spec-
trum, ν, cm–1: 3080 w, 3020 w, 1640 m, 1605 w,
disilazane sodium salt, and 2 g (9.3 mmol) of keto
acetal XVII in 68.8 ml of anhydrous THF. Yield 1.72 g
(87%), light yellow viscous oily substance. IR spec-
trum, ν, cm–1: 3080 w, 1660 m, 1645 m, 1020 s, 910 m.
1H NMR spectrum, δ, ppm: 1.48 m (2H, 8-H), 1.57 s
and 1.62 s (3H each, 2-CH3, 6-CH3), 1.98 m (6H,
CH2C=), 3.04 s (6H, OCH3), 4.25 t (1H, 9-H, J =
5.5 Hz), 4.8 br.s (2H, 1-H), 5.18 t (1H, 5-H, J =
6.0 Hz). Found, %: C 73.12; H 11.81. C13H24O2. Cal-
culated, %: C 73.58; H 11.32.
1
1500 m, 920 m. H NMR spectrum, δ, ppm: 1.24 d
(6H, CH3, J = 6.0 Hz), 1.38 m (4H, CH2), 1.68 s and
1.72 s (3H each, 2-CH3, 6-CH3), 2.06 m (6H, CH2),
2.34 t (2H, 10-H, J = 6.8 Hz), 2.44 m (1H, C6H4CH),
4.8 br.s (2H, 1-H), 5.19 t (1H, 5-H, J = 7.0 Hz), 7.28–
7.36 m (4H, C6H4). Found, %: C 88.54; H 11.31.
C21H32. Calculated, %: C 88.73; H 11.27.
10,10-Dimethoxy-3,7-dimethyldeca-2,6-diene
(XIX) was synthesized as described above for com-
pound IV from 3.68 g (10.3 mmol) of ethyl(triphenyl)-
phosphonium bromide, 4.12 g of hexamethyldisilazane
sodium salt, and 2 g (9.3 mmol) of keto acetal XVII in
68.8 ml of anhydrous THF. Yield 1.8 g (85%), light
yellow viscous oily substance. IR spectrum, ν, cm–1:
b. A solution of 0.18 g of p-isopropylbenzyl
chloride in 15 ml of anhydrous THF was added drop-
wise to a solution of Grignard compound prepared
from 1.2 g (5.2 mmol) of bromide XXVI and 0.12 g of
magnesium in 20 ml of anhydrous THF. The mixture
was heated under reflux until the reactant disappeared
completely (TLC, silica gel, hexane) and was treated
as described above for compound IX. Yield 1.06 g
(72%). Samples of XV synthesized by the two meth-
ods (a and b) were identical in spectral parameters.
1
1660 m, 1650 m, 1020 s. H NMR spectrum, δ, ppm:
1.48 m (2H, 9-H), 1.52 s and 1.57 s (3H each, 3-CH3,
7-CH3), 1.62 d (3H, C1H3), 1.98 m (6H, CH2C=),
3.04 s (6H, OCH3), 4.25 t (1H, 10-H, J = 5.5 Hz),
5.10 t (1H, 6-H, J = 7.0 Hz), 5.28 q (1H, 2-H, J =
7.0 Hz). Found, %: C 74.12; H 11.31. C14H26O2. Cal-
culated, %: C 74.34; H 11.50.
11-(p-Isopropylphenyl)-3,7-dimethylundeca-2,6-
diene (XVI). a. Compound XVI was synthesized as
described above for diene XV by reaction of 2 g
(6.0 mmol) of p-toluenesulfonate XXV with cuprate
prepared from 2.9 ml of a 0.1 M solution of Li2CuCl4
and Grignard compound prepared from 5.8 g of p-iso-
propylbenzyl chloride and 0.97 g of magnesium. Yield
0.92 g (52%). IR spectrum, ν, cm–1: 3020 w, 1640 m,
4,8-Dimethylnona-4,8-dien-1-ol (XXII). A sus-
pension of 0.24 g (6.3 mmol) of LiAlH4 in 15 ml of
anhydrous diethyl ether was cooled to 10°C, 0.96 g
(4.9 mmol) of ester XXX in 15 ml of anhydrous di-
ethyl ether was added dropwise under stirring, and the
mixture was stirred for 0.5 h at 10°C, allowed to warm
up to 20°C, and left to stand for 12 h. The mixture was
then treated with 0.28 ml of water, the organic phase
was separated, and the product was extracted into di-
ethyl ether (2×10 ml). The combined organic extracts
were dried over MgSO4, the drying agent was filtered
off, the solvent was distilled off, and the residue,
0.93 g, was subjected to column chromatography on
silica gel using petroleum ether–ethyl acetate (3:2) as
eluent. Yield 0.78 g (95%), light yellow oily substance.
IR spectrum, ν, cm–1: 3510 br.s, 3050 w, 1642 w,
1
1600 m, 1505 m. H NMR spectrum, δ, ppm: 1.23 d
(6H, CH3, J = 6.0 Hz), 1.30 m (4H, CH2), 1.57 d (3H,
C1H3, J = 6.5 Hz), 1.68 s and 1.72 s (3H each, 3-CH3,
7-CH3), 2.03 m (6H, CH2), 2.35 t (2H, 11-H, J =
6.8 Hz), 2.43 m (1H, C6H4CH), 5.2–5.4 m (2H, 2-H,
5-H), 7.28 br.s (4H, Harom). Found, %: C 88.44;
H 11.53. C22H34. Calculated, %: C 88.59; H 11.41.
b. As described above for compound XV, the reac-
tion of 0.26 g of p-isopropylbenzyl chloride with
Grignard compound prepared from 1.8 g (7.3 mmol) of
bromide XXVII and 0.17 g of magnesium gave 1.73 g
(79%) of XVI. Samples of XVI synthesized by the two
methods (a and b) were identical in spectral param-
eters.
1
1638 m, 915 m. H NMR spectrum, δ, ppm: 1.38 m
(2H, 2-H), 1.64 s and 1.68 s (3H each, 4-CH3, 8-CH3),
1.94–1.98 m (6H, CH2C=), 3.36 t (2H, CH2OH, J =
7.0 Hz), 4.87 br.s (2H, 9-H), 5.12 t (1H, 5-H, J =
6.5 Hz), 5.36 s (1H, OH). Found, %: C 78.69; H 11.76.
C11H20O. Calculated, %: C 78.57; H 11.90.
9,9-Dimethoxy-6-methylnon-5-en-2-one (XVII)
was synthesized according to the procedure described
in [4].
9,9-Dimethoxy-2,6-dimethylnona-1,5-diene
(XVIII) was synthesized as described above for com-
pound IV from 3.54 g (10.0 mmol) of methyl(tri-
phenyl)phosphonium bromide, 4.12 g of hexamethyl-
4,8-Dimethyldeca-4,8-dien-1-ol (XXIII) was syn-
thesized as described above for compound XXII by
reduction of 1.32 g (6.3 mmol) of ester XXXI with
0.24 g of LiAlH4. Yield 1.12 g (98%). IR spectrum, ν,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 6 2010

SYNTHESIS OF ARYL-CONTAINING ISOPRENOIDS
805
1
cm–1: 3460 br.s, 1645 m, 1630 m. H NMR spectrum,
δ, ppm: 1.34 m (2H, 2-H), 1.60 d (3H, C10H3, J =
7.0 Hz), 1.64 s and 1.71 s (3H each, 4-CH3, 8-CH3),
1.90–1.95 m (6H, CH2C=), 3.38 t (2H, CH2OH, J =
7.0 Hz), 5.15 t (1H, 5-H, J = 6.5 Hz), 5.39 q (1H, 9-H,
J = 7.0 Hz), 5.34 br.s (1H, OH). Found, %: C 79.28;
H 12.03. C12H22O. Calculated, %: C 79.12; H 12.09.
dried over MgSO4, filtered, and evaporated. The resi-
due was 0.7 g of alcohol XXIII (IR spectrum, ν, cm–1:
3510 br.s, 1640 m) which was dissolved in 11.7 ml of
anhydrous pyridine. The solution was cooled to 0°C,
1.0 g of p-toluenesulfonyl chloride was added under
stirring, and the mixture was treated as described
above for compound VII to isolate 1.8 g of crude
compound XXV which was purified by column chro-
matography on silica gel using petroleum ether–ethyl
acetate (3:2) as eluent. Yield 1.14 g (88%, calculated
on alcohol XXIII), light yellow oily substance. IR
spectrum, ν, cm–1: 3080 w, 1665 w, 1605 m, 1595 m.
1H NMR spectrum, δ, ppm: 1.46 m (2H, 2-H), 1.60 d
(3H, C10H3, J = 6.5 Hz), 1.62 s and 1.68 s (6H, 4-CH3,
8-CH3), 2.0 m (6H, CH2), 2.30 s (3H, CH3C6H4), 3.69 t
(2H, CH2O, J = 7.0 Hz), 5.10 t (1H, 5-H, J = 7.0 Hz),
5.21 q (1H, 9-H, J = 6.5 Hz), 7.29 d (2H, m-H, J =
8.8 Hz), 8.02 d (2H, o-H, J = 8.8 Hz). Found, %:
C 67.94; H 8.25; S 9.04. C19H28O3S. Calculated, %:
C 67.86; H 8.33; S 9.52.
4,8-Dimethylnona-4,8-dien-1-yl p-toluenesulfo-
nate (XXIV). Acetal XVIII, 1.04 g (4.9 mmol), was
dissolved in 58 ml of anhydrous acetone, 11 ml of
water and 0.32 g of pyridinium p-toluenesulfonate
were added, the mixture was heated for 3 h under
reflux, and aldehyde XX was isolated as described
above for compound V. Yield of XX 0.69 g (IR spec-
trum, ν, cm–1: 2750 m, 1725 s). The product was dis-
solved in 15 ml of anhydrous diethyl ether, the solution
was cooled to 10°C and added dropwise to a suspen-
sion of 0.2 g of LiAlH4 in 10 ml of anhydrous diethyl
ether, and the mixture was stirred for 2 h at 10°C and
carefully decomposed by adding 0.25 ml of water. The
organic phase was separated, and the residue was
washed with diethyl ether. The combined extracts were
dried over MgSO4, filtered, and evaporated to isolate
0.67 g of alcohol XXII (IR spectrum, ν, cm–1:
3510 br.s, 3050 m). Compound XXII without prelimi-
nary purification was dissolved in 11.5 ml of anhy-
drous pyridine, the solution was cooled to 0°C, and 1 g
of p-toluenesulfonyl chloride was added. The mixture
was then treated as described above for compound VII
to isolate 1.58 g of crude product XXIV which was
purified by chromatography on silica gel using
petroleum ether–ethyl acetate (3:2) as eluent. Yield
1.16 g (90%, calculated on alcohol XXII. IR spectrum,
ν, cm–1: 3080 m, 3020 w, 1665 m, 1605 w, 1530 m,
9-Bromo-2,6-dimethylnona-1,5-diene (XXVI).
Carbon tetrabromide, 2.9 g (8.7 mmol), was added at
20°C to a solution of 1.0 g (6.0 mmol) of alcohol XXII
and 2.07 g (7.90 mmol) of triphenylphosphine in 15 ml
of methylene chloride, and the mixture was stirred for
2 h at 20°C and diluted with ethyl acetate. The organic
phase was washed with saturated solutions of NaHCO3
and NaCl and dried over MgSO4, the drying agent was
filtered off, the solvent was distilled off, the residue
was diluted with hexane, the precipitate was filtered
off, and the filtrate was evaporated to isolate 1.64 g of
crude product XXVI which was purified by column
chromatography on silica gel using hexane as eluent.
Yield 1.29 g (94%), light yellow oily liquid. IR spec-
trum, ν, cm–1: 3030 w, 1645 m, 1015 m, 905 m, 685 m.
1H NMR spectrum, δ, ppm: 1.60 m (2H, 8-H), 1.68 s
and 1.74 s (6H, 2-CH3, 6-CH3), 1.94–2.06 m (6H,
CH2), 3.35 t (2H, CH2Br, J = 7.0 Hz), 4.91 br.s (2H,
1-H), 5.13 t (1H, 5-H, J = 6.5 Hz). Found, %: C 57.06;
H 8.34; Br 34.91. C11H19Br. Calculated, %: C 57.14;
H 8.23; Br 34.63.
1
930 m. H NMR spectrum, δ, ppm: 1.46 m (2H, 2-H),
1.62 s and 1.68 s (3H each, 4-CH3, 8-CH3), 2.08 m
(6H, CH2C=), 2.30 s (3H, CH3C6H4), 3.69 t (2H,
CH2O, J = 7.0 Hz), 4.88 br.s (2H, 9-H), 5.21 t (1H,
5-H, J = 77.0 Hz), 7.29 d (2H, m-H, J = 8.8 Hz), 8.02 d
(2H, o-H, J = 8.8 Hz). Found, %: C 67.24; H 8.14;
S 9.49. C18H26O3S. Calculated, %: C 67.08; H 8.07;
S 9.94.
10-Bromo-3,7-dimethyldeca-2,6-diene (XXVII)
was synthesized from 1.1 g (6.0 mmol) of alcohol
XXIII and 2.9 g (8.70 mmol) of carbon tetrabromide
in 18 ml of anhydrous methylene chloride in the pres-
ence of 2.07 g (7.90 mmol) of triphenylphosphine. The
product was isolated and purified as described above
for compound XXVI. Yield 1.41 g (94%), light yellow
oily substance. IR spectrum, ν, cm–1: 1650 m, 1020 m,
4,8-Dimethyldeca-4,8-dien-1-yl p-toluenesulfo-
nate (XXV). A solution of 0.74 g (4.1 mmol) of alde-
hyde XXI (prepared from compound XIX according to
the procedure described above for the synthesis of XX)
in 15 ml of anhydrous diethyl ether was cooled to
10°C and added dropwise to a suspension of 0.2 g of
LiAlH4 in 10 ml of anhydrous diethyl ether. The mix-
ture was stirred for 2 h at 10°C and carefully treated
with 0.6 ml of water. The organic phase was separated,
1
680 m. H NMR spectrum, δ, ppm: 1.36 m (2H, 9-H),
1.59 d (3H, C1H3, J = 6.5 Hz), 1.65 s and 1.72 s (6H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 6 2010

KUKOVINETS et al.
806
3-CH3, 7-CH3), 1.94–2.06 m (6H, CH2), 3.38 t (2H,
CH2Br, J = 7.0 Hz), 5.2–5.3 m (2H, 6-H). Found, %:
C 58.93; H 8.39; Br 32.71. C12H21Br. Calculated, %:
C 58.78; H 8.57; Br 32.65.
phosphonium bromide and 3.32 g of hexamethyl-
disilazane sodium salt in 55 ml of anhydrous THF as
described above for compound IV. Yield 1.14 g (77%),
colorless viscous oily substance. IR spectrum, ν, cm–1:
1
3080 w, 1745 s, 1645 w, 1640 m, 915 m. H NMR
4-Methyl-8-oxonon-4-enoic acid (XXVIII).
An ozone–oxygen mixture was passed through a solu-
tion of 5 g (36.8 mmol) of 1,5-cycloocta-1,5-diene (II)
in a mixture of 50 ml of cyclohexane and 2.7 ml of
acetic acid under continuous stirring at 0–5°C until
ozone appeared at the outlet of the reactor (iodine–
starch test). The mixture was purged with argon, cyclo-
hexane was separated from the oily material by
decanting, and 8.3 ml of acetic anhydride was added to
the residue (peroxide product) under stirring at 5°C.
The mixture was allowed to warm up to 15°C, a mix-
ture of 3.6 g (57.8 mmol) of sodium acetate and 17 ml
of acetic acid was added under stirring, the mixture
was stirred for 30 min at 15°C, 8.3 ml of water was
added, and the mixture was heated for 30 min at the
boiling point, cooled to 20°C, and kept for 12 h at that
temperature. Acetic acid was distilled off under
reduced pressure, 190 ml of a 1:1 benzene–diethyl
ether mixture was added to the residue, and the precip-
itate was filtered off. The filtrate was washed with
a saturated solution of sodium chloride and dried over
MgSO4. The drying agent was filtered off, the solvent
was distilled off, and the residue was subjected to
chromatography on silica gel using petroleum ether–
ethyl acetate (3:1) as eluent. Yield 6.29 g (93%), color-
less amorphous substance. IR spectrum, ν, cm–1: 2400–
spectrum, δ, ppm: 1.64 s and 1.72 s (3H each, 4-CH3,
8-CH3), 1.98–2.45 m (8H, CH2), 3.59 s (3H, OCH3),
4.87 br.s (2H, 9-H), 5.24 t (1H, 6-H, J = 7.0 Hz).
Found, %: C 73.64; H 10.06. C12H20O2. Calculated, %:
C 73.47; H 10.20.
Methyl 4,8-dimethyldeca-4,8-dienoate (XXXI)
was synthesized by reaction of 2.0 g (10.1 mmol) of
oxo ester XXIX with ethylidene(triphenyl)phospho-
rane [generated from 3.95 g (10.6 mmol) of ethyl(tri-
phenyl)phosphonium bromide and 13 ml of a 1.4 M
solution of n-BuLi in hexane] at –70°C in 40 ml of
anhydrous THF under argon. The product was isolated
as described above for compound IV. Yield 1.59 g
(75%), colorless viscous oily substance. IR spectrum,
ν, cm–1: 1745 s, 1645 w, 1640 m. 1H NMR spectrum, δ,
ppm: 1.64 d (3H, C10H3, J = 6.5 Hz), 1.68 s and 1.72 s
(3H each, 4-CH3, 8-CH3), 1.9–2.0 m (6H, CH2), 2.42 t
(2H, 2-H, J = 7.0 Hz), 3.61 s (3H, OCH3), 5.13 t
(1H, 5-H, J = 7.0 Hz), 5.26 q (1H, 9-H, J = 6.5 Hz).
Found, %: C 74.41; H 10.36. C13H22O2. Calculated, %:
C 74.29; H 10.48.
REFERENCES
1. Silverstein, R.M., Science, 1981, vol. 213, no. 4514,
p. 1326.
1
3200 br.s, 1715 s, 1700 s, 1640 m, 900 s. H NMR
2. Serebryakov, E.P. and Promonenko, V.K., Itogi Nauki
Tekh., Org. Khim., 1989, vol. 9, p. 137.
3. Schwarz, M. and Miller, R.W., J. Med. Entomol., 1979,
vol. 15, p. 300; Ref. Zh., Khim., 1979, no. 21O340.
4. Odinokov, V.N., Zainullin, R.A., Sultanmuratova, V.R.,
and Tolstikov, G.A., Zh. Org. Khim., 1988, vol. 24,
p. 1365.
spectrum, δ, ppm: 1.62 s (3H, 4-CH3), 2.08 s (3H,
C9H3), 1.9–2.6 m (8H, CH2), 5.12 t (1H, 6-H, J =
7.0 Hz), 10.9 s (1H, COOH). Found, %: C 65.34;
H 8.56. C10H16O3. Calculated, %: C 65.22; H 8.70.
Methyl 4,8-dimethylnona-4,8-dienoate (XXX)
was synthesized by reaction of 1.5 g (7.8 mmol) of oxo
ester XXIX with methylidene(triphenyl)phosphorane
generated from 2.85 g (8.0 mmol) of methyl(triphenyl)-
5. Odinokov, V.N., Kukovinets, O.S., Zainullin, R.A., and
Tolstikov, G.A., Zh. Org. Khim., 1989, vol. 25, p. 725.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 6 2010