Synthesis of kairomones and their analogs from 2-acylcyclohexane-1,3-diones with an unsaturated acyl side chain

Article abstract of DOI:10.1134/S1070428008100084

Natural 2-[(9Z)-1-oxooctadec-9-en-1-yl]-, 2-[(9Z,12Z)-1-oxooctadeca-9,12- dien-1-yl]-, and 2-[(9Z,12Z,15Z)-1-oxooctadeca-9,12,15-trien-1-yl]cyclohexane-1, 3-diones (components of flour moth Ephestia kuehniella kairomones) and some their analogs were synthesized from cyclohexane-1,3-diones and long-chain unsaturated carboxylic acid chlorides.

Full text of DOI:10.1134/S1070428008100084

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 10, pp. 1444–1450. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © F.A. Lakhvich, I.I. Petrusevich, N.G. Ogeiko, A.N. Sergeeva, 2008, published in Zhurnal Organicheskoi Khimii, 2008, Vol. 44,
No. 10, pp. 1468–1468.
Synthesis of Kairomones and Their Analogs from 2-Acylcyclo-
hexane-1,3-diones with an Unsaturated Acyl Side Chain
F. A. Lakhvich, I. I. Petrusevich, N. G. Ogeiko, and A. N. Sergeeva
Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus,
ul. Akademika Kuprevicha 5/2, Minsk, 220141 Belarus
e-mail: ogeiko@rambler.ru
Received December 25, 2007
Abstract—Natural 2-[(9Z)-1-oxooctadec-9-en-1-yl]-, 2-[(9Z,12Z)-1-oxooctadeca-9,12-dien-1-yl]-, and
2-[(9Z,12Z,15Z)-1-oxooctadeca-9,12,15-trien-1-yl]cyclohexane-1,3-diones (components of flour moth Ephestia
kuehniella kairomones) and some their analogs were synthesized from cyclohexane-1,3-diones and long-chain
unsaturated carboxylic acid chlorides.
DOI: 10.1134/S1070428008100084
The presence of a cyclic β,β′-tricarbonyl fragment
is typical of many biorganic compounds produced by
plants, microorganisms, and insects [1, 2]. Among
these, the most interesting are kairomones isolated
recently from some Lepidoptera and Hemiptera species
and protecting substances, namely 2-acylcyclohexane-
1,3-diones and their 4-hydroxy derivatives having in
the side acyl chain saturated or unsaturated C12, C14,
C16, C18, or C20 fragments with different positions and
configurations of the double bonds [3, 4]. Analogous
compounds were also isolated from plants [5, 6]; how-
ever, their biological function still remains unclear. At-
tempts to synthesize compounds I (X = H, R = C17H33,
C17H31) gave no results of preparative value [7].
R = n-C11H23, n-C13H27, n-C15H31, n-C17H35, n-C19H39,
n-C21H43) and their analogs differing by the structure
of the side chain or cyclic fragment (having one or two
methyl groups on C5 in the cyclohexane ring) [9].
OH
O
R
O
X
I
The present article describes the synthesis of natu-
ral 2-acylcyclohexane-1,3-diones having an unsaturat-
ed acyl side chain and synthetic approaches to their
analogs. By reactions of β-diketones IIa–IIc with
oleoyl, linoleoyl, linolenoyl, and undec-10-enoyl
chlorides III–VI we synthesized the corresponding
enol esters VII–X (Scheme 1) in 87–100% yield. Their
structure was unambiguously confirmed by the IR and
Following a simple procedure for the synthesis of
cyclic β-triketones via O→C migration of the acyl
group in enol esters derived from cyclohexane-1,3-
diones, which was developed by us previously [8], we
obtained a series of natural compounds like I (X = H,
Scheme 1.
H
·
·
·
O
O
O
O
Et3N, MeCN, Me2C(OH)CN
or DMAP, NaOAc
O
R3
Pyridine, CHCl3
+
R3COCl
R1
R2
R1
R2
R1
R2
XIa–XIc, XIIa–XIIc
XIIIa–XIIIc, XIVa–XIVc
O
O
R3
O
IIa–IIc
III–VI
VIIa–VIIc, VIIIa–VIIIc
IXa–IXc, Xa–Xc
R1 = R2 = H (a); R1 = Me, R2 = H (b); R1 = R2 = Me (c); III, VII, XI, R3 = (9Z)-C17H33; IV, VIII, XII, R3 = (9Z,12Z)-C17H31;
V, IX, XIII, R3 = (9Z,12Z,15Z)-C17H29; VI, X, XIV, R3 = CH2=CH(CH2)8.
1444

SYNTHESIS OF KAIROMONES AND THEIR ANALOGS
1445
Scheme 2.
O
O
Pyridine, CHCl3
O
+
(9E)-C17H33COCl
R1
R2
R1
R2
Me
( )6
O
O
IIa, IIc
XV
XVIa, XVIc
OH
O
Me
DMAP, NaOAc
( )6
R1
R2
O
XVIIa, XVIIc
1H NMR data which were consistent with available
published data for structurally related compounds.
However, we failed to effect O–C isomerization of
enol esters VII–X by the action of AlCl3. After treat-
ment of the reaction mixture under the conditions de-
scribed in [9] for decomposition of the complex with
aluminum chloride (with a mixture of ice and concen-
trated hydrochloric acid), we isolated initial β-di-
ketones IIa–IIc and the corresponding fatty acids.
on heating for 0.5–6 h. The yields of 2-acylcyclo-
hexane-1,3-diones XI–XIV, XVII, and XXV–XXVII
reached 100% in acetonitrile in the presence of
2-hydroxy-2-methylpropanenitrile and triethylamine
[10, 11]. The synthesis of XIa and XIIa according to
the procedure described in [8] through O–C isomeriza-
tion of enol esters VIIa and VIIIa in the presence of
4-(pyrrolidin-1-yl)pyridine ensured only 30% yield of
the target triketones [12].
Attempted direct acylation of dihydroresorcinol
(IIa) with oleic anhydride in the presence of boron tri-
fluoride–ether complex [7] resulted in the formation of
a mixture of 2-oleoylcyclohexane-1,3-dione (XIa) and
its E isomer XVIIa in an overall yield of 18%. O–C
Isomerization of enol ester VIIa to 2-oleoylcyclo-
hexane-1,3-dione (XIa) occurred in 66% yield when
the substrate was fused with anhydrous sodium acetate
at 160–180°C in an inert atmosphere. The reaction was
not accompanied by isomerization of the double bond;
this was proved by independent synthesis of the corre-
sponding E isomer XVIIa. For this purpose, enol ester
XVIa obtained by acylation of β-diketone IIa with
(9E)-octadec-9-enoyl chloride (XV) was subjected to
O–C isomerization by the action of sodium acetate
under the same conditions (Scheme 2).
As we showed previously [9], the reactions of un-
symmetrical β-diketone, methyl 2,2-dimethyl-4,6-di-
oxocyclohexane-1-carboxylate (XVIII) with acid chlo-
rides III, IV, and VI gave mixtures of regioisomeric
enol esters XIX–XXI and XXII–XXIV due to acyla-
tion of two isomeric enols derived from the initial
β-diketone. The ratio of isomers XIX–XXIV can be
determined on the basis of signal intensities of the CH
and CH2 protons in the cyclohexene ring. However,
O–C isomerization of enol esters XIX–XXIV leads to
the same triketones XXV–XXVII; therefore, prelimi-
nary separation of isomeric enol esters is unnecessary
(Scheme 3).
Following the above procedure, the O–C isomeriza-
tion of enol esters VIIa and VIIb obtained from di-
ketones IIa and IIb and oleic and linolenic acid chlo-
rides III and IV gave 87–100% of the corresponding
β-triketones which were identical to the natural com-
pounds.
The presence in the IR spectrum of XVIIa of
an absorption band at 965 cm–1 and the absence of
such band in the spectrum of XIa, as well as the
chemical shifts of the double-bonded carbon atoms in
the 13C NMR spectra (δC 32.5 ppm for XVIIa and
27.0 ppm for XIa) indicated that in both cases the
configuration of the double bond is conserved.
With a view to obtain analogs of kairomones XIa
and XIIa, differing by the structure of the side chain
and cyclic fragment, we synthesized enol esters IXb,
IXc, Xb, and Xc by reactions of cyclohexane-1,3-di-
ones IIb and IIc with linolenic acid chloride (V) and
undec-10-enoyl chloride (VI). Their structure was con-
Further optimization of the conditions for O–C-iso-
merization of enol esters VII–X, XVI, and XIX–
XXIV showed that the best results are obtained using
4-dimethylaminopyridine (DMAP) as catalyst. In this
case, the reaction is carried out in benzene or toluene
1
firmed by the IR and H NMR spectra. The IR spectra
of IXb, IXc, Xb, and Xc contained absorption bands
due to stretching vibrations of the ester (1765 cm–1)
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 10 2008

LAKHVICH et al.
1446
Scheme 3.
O
O
O
MeOCO
Me
Pyridine, CHCl3
O
O
+
R3COCl
+
Me
Me
Me
Me
O
O
R3
O
R3
Me
COOMe
XVIII
COOMe
XIX–XXI
III, IV, VI
XXII–XXIV
· · ·
· · ·
OH
O
O
OH
O
O
O
O
R3
MeO
Me
Me
R3
MeO
Me
Me
R3
Me
Me
O
O
O
COOMe
A
B
XXV–XXVII
and conjugated carbonyl groups (1680 cm–1) and
elemental compositions of the products coincided with
those calculated for the assumed structures. The sol-
vents were dehydrated and purified according to stand-
ard procedures. The progress of reactions was moni-
tored by TLC on Silufol UV-254 plates using hexane–
diethyl ether (1:1).
1
C–O–C fragment (1120 cm–1). In the H NMR spectra
of these compounds we observed signals from the
olefinic proton at δ 5.68–5.90 ppm, terminal methyl
group at δ 0.88–0.89 ppm, and methyl groups in the
cyclohexane ring at δ 1.10–1.12 ppm. Protons in the
other molecular fragments had their usual chemical
shifts.
O-Acyl derivatives VIIa–VIIc, VIIIa–VIIIc,
IXa–IXc, Xa–Xc, XVIa, XVIc, and XIX–XXIV
(general procedure). A solution of 0.11 mol of carbox-
ylic acid chloride III–VI or XV in chloroform was
added dropwise over a period of 1.5 h under stirring at
room temperature to a mixture of 0.1 mol of the
corresponding diketone IIa–IIc or XVIII and 0.1 mol
of pyridine in anhydrous chloroform. The mixture was
diluted with chloroform, treated in succession with
dilute (1:10) hydrochloric acid, a saturated solution of
sodium carbonate, and water (100 ml each), dried over
magnesium sulfate, and filtered, and the filtrate was
evaporated.
Enol esters IXb, IXc, Xb, and Xc were subjected to
O–C isomerization by the action of DMAP or 2-hy-
droxy-2-methylpropanenitrile, and the resulting β-tri-
ketones XIIIb, XIIIc, XIVb, and XIVc (yield 75–
100%) were characterized by IR and 1H NMR spectra.
The spectral data indicated that the products exist in
the enol form with strong intramolecular hydrogen
bond. The enol proton resonated in the 1H NMR spec-
tra in a very weak field (δ 17–18 ppm), and the IR
spectra contained absorption bands at 1560 and
1670 cm–1 due to stretching vibrations of the chelated
and conjugated carbonyl groups.
3-Oxocyclohex-1-en-1-yl (9Z)-octadec-9-enoate
(VIIa). Yield 98%. IR spectrum, ν, cm–1: 1765 (C=O,
ester), 1680 (C=O), 1645 (C=C), 1120 (C–O–C).
1H NMR spectrum, δ, ppm: 0.88 t (3H, CH3, J =
6.5 Hz), 1.33 br.s (20H, CH2), 1.65–1.68 m (2H, CH2),
1.97–2.01 m (4H, CH2), 2.07–2.09 m (2H, CH2), 2.41 t
(2H, CH2, J = 7.0 Hz), 2.45 t (2H, CH2, J = 7.0 Hz),
2.93 t (2H, CH2, J = 7.5 Hz), 5.31–5.33 m (2H, CH),
5.88 s (1H, CH). Found, %: C 76.55; H 10.71.
C24H40O3. Calculated, %: C 76.68; H 10.76.
Biological testing of the synthesized compounds
showed that they exert synergistic or inhibitory effect
on known insect pheromones or kairomones, depend-
ing on the dose, formulation composition, and mode of
administration.
EXPERIMENTAL
The NMR spectra were recorded on Bruker AT-200,
Bruker WM-360, and Bruker BioSpin Avance-500
spectrometers from solutions in chloroform-d using
tetramethylsilane as internal reference. The IR spectra
were measured on a UR-20 instrument from samples
prepared as KBr pellets or films (neat). The melting
points were determined on a Boetius hot stage. The
5-Methyl-3-oxocyclohex-1-en-1-yl (9Z)-octadec-
9-enoate (VIIb). Yield 95%. IR spectrum, ν, cm–1:
1765 (C=O, ester), 1675 (C=O), 1645 (C=C), 1120
(C–O–C). 1H NMR spectrum, δ, ppm: 0.88 t (3H, CH3,
J = 6.5 Hz), 1.10 d (3H, CH3, J = 6.5 Hz), 1.24 br.s
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 10 2008

SYNTHESIS OF KAIROMONES AND THEIR ANALOGS
1447
(20H, CH2), 1.58–1.60 m (2H, CH2), 1.92–1.96 m (4H,
CH2), 2.09–2.11 m (1H, CH), 2.31–2.33 m (2H, CH2),
2.40–2.42 m (2H, CH2), 2.53 t (2H, CH2, J = 7.5 Hz),
5.21–5.24 m (2H, CH), 5.68 s (1H, CH). Found, %:
C 76.87; H 10.84. C25H42O3. Calculated, %: C 76.78;
H 10.86.
cm–1: 1770 (C=O, ester), 1685 (C=O), 1650 (C=C),
1130 (C–O–C). 1H NMR spectrum, δ, ppm: 0.98 t (3H,
CH3, J = 7.0 Hz), 1.33 br.s (12H, CH2), 1.65–1.68 m
(2H, CH2), 2.08 m (4H, CH2), 2.41 t (2H, CH2, J =
6.5 Hz), 2.46 m (2H, CH2), 2.53 t (2H, CH2, J =
7.0 Hz), 2.81 t (2H, CH2, J = 7.5 Hz), 5.33–5.37 m
(6H, CH), 5.89 s (1H, CH). Found, %: C 77.38;
H 9.74. C24H36O3. Calculated, %: C 77.31; H 9.68.
5,5-Dimethyl-3-oxocyclohex-1-en-1-yl (9Z)-octa-
dec-9-enoate (VIIc). Yield 97%. IR spectrum, ν, cm–1:
1765 (C=O, ester), 1680 (C=O), 1645 (C=C), 1120
(C–O–C). 1H NMR spectrum, δ, ppm: 0.89 t (3H, CH3,
J = 6.5 Hz), 1.11 s (6H, CH3), 1.25 br.s (20H, CH2),
1.64–1.68 m (2H, CH2), 1.98–2.02 m (4H, CH2), 2.26 s
(2H, CH2), 2.41 s (2H, CH2), 2.45 t (2H, CH2, J =
7.5 Hz), 5.30–5.35 m (2H, CH), 5.91 s (1H, CH).
Found, %: C 77.18; H 10.96. C26H44O3. Calculated, %:
C 77.14; H 10.60.
5, 5-Dimethyl-3-oxocyclohex-1-en-1-yl
(9Z,12Z,15Z)-octadeca-9,12,15-trienoate (IXc). Yield
94%. IR spectrum, ν, cm–1: 1770 (C=O, ester), 1685
1
(C=O), 1650 (C=C), 1125 (C–O–C). H NMR spec-
trum, δ, ppm: 0.98 t (3H, CH3, J = 7.0 Hz), 1.11 s (6H,
CH3), 1.33 br.s (12H, CH2), 1.68 m (2H, CH2), 2.08 m
(4H, CH2), 2.27 s (2H, CH2), 2.41 s (2H, CH2), 2.81 t
(2H, CH2, J = 7.5 Hz), 5.30–5.37 m (6H, CH), 5.90 s
(1H, CH). Found, %: C 77.95; H 10.06. C26H40O3.
Calculated, %: C 77.88; H 10.16.
3-Oxocyclohex-1-en-1-yl (9Z,12Z)-octadeca-9,12-
dienoate (VIIIa). Yield 98%. IR spectrum, ν, cm–1:
1770 (C=O, ester), 1680 (C=O), 1645 (C=C), 1125
(C–O–C). 1H NMR spectrum, δ, ppm: 0.89 t (3H, CH3,
J = 6.5 Hz), 1.31 br.s (14H, CH2), 1.65–1.68 m (2H,
CH2), 1.97–2.01 m (4H, CH2), 2.07–2.09 m (2H, CH2),
2.41 t (2H, CH2, J = 7.0 Hz), 2.45 t (2H, CH2, J =
7.0 Hz), 2.45 t (2H, CH2, J = 7.0 Hz), 2.77 t (2H, CH2,
J = 7.5 Hz), 5.29–5.36 m (4H, CH), 5.88 s (1H, CH).
Found, %: C 76.96; H 10.23. C24H38O3. Calculated, %:
C 76.90; H 10.21.
3-Oxocyclohex-1-en-1-yl undec-10-enoate (Xa).
Yield 94%. IR spectrum, ν, cm–1: 1765 (C=O, ester),
1
1680 (C=O), 1645 (C=C), 1125 (C–O–C). H NMR
spectrum, δ, ppm: 1.33 br.s (10H, CH2), 1.65–1.68 m
(2H, CH2), 2.04–2.08 m (2H, CH2), 2.41 t (2H, CH2,
J = 7.0 Hz), 2.46 t (2H, CH2, J = 7.0 Hz), 2.51–2.53 m
(2H, CH2), 2.81 t (2H, CH2, J = 7.5 Hz), 4.95 d.d (2H,
CH2, J = 17.0, 28.0 Hz), 5.71–5.75 m (1H, CH), 5.89 s
(1H, CH). Found, %: C 73.34; H 9.41. C17H26O3. Cal-
culated, %: C 73.38; H 9.40.
5-Methyl-3-oxocyclohex-1-en-1-yl (9Z,12Z)-octa-
deca-9,12-dienoate (VIIIb). Yield 96%. IR spectrum,
ν, cm–1: 1765 (C=O, ester), 1675 (C=O), 1650 (C=C),
5-Methyl-3-oxocyclohex-1-en-1-yl undec-10-
enoate (Xb). Yield 98%. IR spectrum, ν, cm–1: 1770
(C=O, ester), 1670 (C=O), 1645 (C=C), 1125
1
1120 (C–O–C). H NMR spectrum, δ, ppm: 0.89 t
1
(C–O–C). H NMR spectrum, δ, ppm: 1.12 d (3H,
(3H, CH3, J = 6.5 Hz), 1.12 d (3H, CH3, J = 6.5 Hz),
1.30 br.s (16H, CH2), 1.58–1.60 m (2H, CH2), 1.92–
1.96 m (4H, CH2), 2.09–2.11 m (1H, CH), 2.31–
2.33 m (2H, CH2), 2.40–2.42 m (2H, CH2), 2.53 t (2H,
CH2, J = 7.5 Hz), 5.21–5.33 m (4H, CH), 5.68 s (1H,
CH). Found, %: C 77.27; H 10.38. C25H40O3. Calcu-
lated, %: C 77.20; H 10.30.
CH3, J = 6.5 Hz), 1.33 br.s (10H, CH2), 1.51–1.56 m
(2H, CH2), 1.91–1.98 m (2H, CH2), 2.11–2.14 m (1H,
CH), 2.48–2.50 m (4H, CH2), 2.54 t (2H, CH2, J =
7.5 Hz), 4.90 d.d (2H, CH, J = 17.0, 28.0 Hz), 5.70–
5.74 m (1H, CH), 5.90 s (1H, CH). Found, %: C 73.93;
H 9.65. C18H28O3. Calculated, %: C 73.86; H 9.60.
5,5-Dimethyl-3-oxocyclohex-1-en-1-yl undec-10-
enoate (Xc). Yield 98%. IR spectrum, ν, cm–1: 1765
(C=O, ester), 1680 (C=O), 1645 (C=C), 1120
5,5-Dimethyl-3-oxocyclohex-1-en-1-yl (9Z,12Z)-
octadeca-9,12-dienoate (VIIIc). Yield 97%. IR spec-
trum, ν, cm–1: 1770 (C=O, ester), 1680 (C=O), 1650
1
1
(C–O–C). H NMR spectrum, δ, ppm: 1.12 s (6H,
(C=C), 1120 (C–O–C). H NMR spectrum, δ, ppm:
CH3), 1.34 br.s (10H, CH2), 1.65–1.68 m (2H, CH2),
2.01–2.04 m (2H, CH2), 2.42 s (2H, CH2), 2.46 s (2H,
CH2), 2.54 t (2H, CH2, J = 7.5 Hz), 4.95 d.d (2H, CH2,
1J = 17.0, 2J = 28.0 Hz), 5.78–5.80 m (1H, CH), 5.90 s
(1H, CH). Found, %: C 74.47; H 9.87. C19H30O3. Cal-
culated, %: C 74.41; H 9.84.
0.91 t (3H, CH3, J = 6.5 Hz), 1.11 s (6H, CH3),
1.31 br.s (16H, CH2), 1.68 m (2H, CH2), 1.98–2.03 m
(4H, CH2), 2.26 s (2H, CH2), 2.41 s (2H, CH2), 2.45 t
(2H, CH2, J = 7.5 Hz), 5.30–5.35 m (4H, CH), 5.90 s
(1H, CH). Found, %: C 77.56; H 10.51. C26H42O3. Cal-
culated, %: C 77.50; H 10.48.
3-Oxocyclohex-1-en-1-yl (9Z,12Z,15Z)-octadeca-
9,12,15-trienoate (IXa). Yield 92%. IR spectrum, ν,
3-Oxocyclohex-1-en-1-yl (9E)-octadec-9-enoate
(XVIa). Yield 75%, mp 25°C. IR spectrum, ν, cm–1:
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 10 2008

LAKHVICH et al.
1448
1770 (C=O, ester), 1685 (C=O), 1645 (C=C), 1120
(C–O–C). 1H NMR spectrum, δ, ppm: 0.89 t (3H, CH3,
J = 6.5 Hz), 1.33 br.s (20H, CH2), 1.62–1.66 m (2H,
CH2), 1.97–2.07 m (4H, CH2), 2.07–2.09 m (2H, CH2),
2.45 t (2H, CH2, J = 7.0 Hz), 2.52 t (2H, CH2, J =
7.0 Hz), 2.83 t (2H, CH2, J = 7.5 Hz), 5.34–5.38 m
(2H, CH), 5.89 s (1H, CH). Found, %: C 76.55;
H 10.71. C24H40O3. Calculated, %: C 76.52; H 10.64.
3-ene-1-carboxylate (XXIV). Yield 94%. IR spec-
trum, ν, cm–1: 1765 (C=O, ester), 1680 (C=O), 1645
(C=C), 1120 (C–O–C). H NMR spectrum, δ, ppm:
1
1.08 s and 1.10 s (6H, CH3), 1.34 br.s (10H, CH2),
1.64–1.68 m (2H, CH2), 1.98–2.02 m (2H, CH2), 2.41 s
and 2.46 s (2H, CH2), 2.45 t (2H, CH2, J = 7.5 Hz),
3.26 s and 3.30 s (1H, CH), 3.73 s and 3.75 s (3H,
CH3), 4.95 d.d (2H, CH2, J = 17.0, 28.0 Hz), 5.78–
5.80 m (1H, CH), 5.91 s and 5.93 s (1H, CH). Found,
%: C 69.20; H 8.85. C21H32O5. Calculated, %: C 69.11;
H 8.81.
5,5-Dimethyl-3-oxocyclohex-1-en-1-yl (9E)-octa-
dec-9-enoate (XVIc). Yield 97%, mp 36–39°C. IR
spectrum, ν, cm–1: 1770 (C=O, ester), 1680 (C=O),
1
1645 (C=C), 1115 (C–O–C). H NMR spectrum, δ,
Triketones XIa–XIc, XIIa–XIIc, XIIIa–XIIIc,
XIVa–XIVc, XVIIa, and XXV (general procedure).
a. A mixture of 0.0032 mol of compound VIIa and
0.0032 mol of anhydrous (fused) sodium acetate was
heated for 30 min 160–170°C in an inert atmosphere
until it became a homogeneous liquid. The dark red
melt was cooled and dissolved on grinding in 150 ml
of diethyl ether, the solution was washed with water
(2×50 ml) and dried over magnesium sulfate, the sol-
vent was removed, and the residue (if necessary) was
purified by column chromatography on silica gel L
(40–100 μm). Elution with hexane–ether (2:1) gave
0.8 g (66%) of XIa as an oily substance which crystal-
lized on storage in a refrigerator, mp 10°C.
ppm: 0.88 t (3H, CH3, J = 6.5 Hz), 1.11 s (6H, CH3),
1.29 br.s (20H, CH2), 1.65–1.68 m (2H, CH2), 1.95–
1.99 m (4H, CH2), 2.28 s (2H, CH2), 2.41 s (2H, CH2),
2.44 t (2H, CH2, J = 7.5 Hz), 5.30–5.38 m (2H, CH),
5.89 s (1H, CH). Found, %: C 77.18; H 10.96.
C26H44O3. Calculated, %: C 77.10; H 10.84.
Methyl 6,6-dimethyl-2-[(9Z)-octadec-9-enoyl-
oxy]-4-oxocyclohex-2-ene-1-carboxylate (XIX) and
methyl 6,6-dimethyl-4-[(9Z)-octadec-9-enoyloxy]-2-
oxocyclohex-3-ene-1-carboxylate (XXII). Yield 87%.
IR spectrum, ν, cm–1: 1765 (C=O, ester), 1680 (C=O),
1
1645 (C=C), 1120 (C–O–C). H NMR spectrum, δ,
ppm: 0.87 t (3H, CH3, J = 6.5 Hz); 1.08 s, 1.11 s,
1.14 s, and 1.17 s (6H, CH3); 1.28 br.s (20H, CH2);
1.64–1.68 m (2H, CH2); 1.98–2.02 m (4H, CH2);
2.41 s and 2.46 s (2H, CH2); 2.45 t (2H, CH2, J =
7.5 Hz); 3.26 s and 3.30 s (1H, CH); 3.73 s and 3.75 s
(3H, CH3); 5.30–5.35 m (2H, CH); 5.91 s and 5.93 s
(1H, CH). Found, %: C 72.69; H 10.02. C28H46O5. Cal-
culated, %: C 77.56; H 10.12.
b. Enol ester VIIa–VIIc, VIIIa–VIIIc, IXa–IXc,
Xa–Xc, XVIa, XIX, or XXII, 0.001 mol, was dis-
solved in 100 ml of benzene, 0.007 mol of 4-dimethyl-
aminopyridine was added, and the mixture was heated
for 1–6 h under reflux (the progress of the reaction was
monitored by TLC). The mixture was cooled and
treated with dilute hydrochloric acid and water (100 ml
each), the organic phase was dried over magnesium
sulfate, and the solvent was removed to obtain com-
pounds XIa–XIc, XIIa–XIIc, XIIIa–XIIIc, XIVa–
XIVc, XVIIa, and XXV which were purified by pre-
parative column chromatography (silica gel, 100 µm,
hexane–diethyl ether, 9:1).
Methyl 6,6-dimethyl-2-[(9Z,12Z)-octadeca-9,12-
dienoyloxy]-4-oxocyclohex-2-ene-1-carboxylate
(XX) and methyl 6,6-dimethyl-4-[(9Z,12Z)-octa-
deca-9,12-dienoyloxy]-2-oxocyclohex-3-ene-1-car-
boxylate (XXIII). Yield 94%. IR spectrum, ν, cm–1:
1765 (C=O, ester), 1680 (C=O), 1645 (C=C), 1120
(C–O–C). 1H NMR spectrum, δ, ppm: 0.89 t (3H, CH3,
J = 6.5 Hz); 1.08 s, 1.11 s, 1.14 s, and 1.16 s (6H,
CH3); 1.33 br.s (16H, CH2); 1.64–1.68 m (2H, CH2);
1.98–2.02 m (4H, CH2); 2.41 s and 2.46 s (2H, CH2);
2.45 t (2H, CH2, J = 7.5 Hz); 3.26 s and 3.30 s (1H,
CH); 3.73 s and 3.75 s (3H, CH3); 5.30–5.35 m (4H,
CH); 5.91 s and 5.93 s (1H, CH). Found, %: C 73.01;
H 9.63. C28H44O5. Calculated, %: C 73.10; H 9.58.
c. Enol ester VIIa–VIIc, VIIIa–VIIIc, IXa–IXc,
Xa–Xc, XVIa, XIX, or XXII, 0.001 mol, was dis-
solved in 10 ml of acetonitrile, 0.002 mol of triethyl-
amine and 0.1 ml of 2-hydroxy-2-methylpropanenitrile
were added, and the mixture was stirred for 18 h.
Volatile substances were distilled off on a rotary evap-
orator, the oily residue was dissolved in 100 ml of
chloroform, the solution was washed with dilute
(1 : 10) hydrochloric acid (3 × 100 ml) and water
(2×100 ml) and dried over magnesium sulfate, the
solvent was removed, and the residue was purified by
column chromatography (hexane–diethyl ether, 9:1) to
Methyl 6,6-dimethyl-4-oxo-2-(undec-10-enoyl-
oxy)cyclohex-2-ene-1-carboxylate (XXI) and methyl
6,6-dimethyl-2-oxo-4-(undec-10-enoyloxy)cyclohex-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 10 2008

SYNTHESIS OF KAIROMONES AND THEIR ANALOGS
1449
isolate compounds XIa–XIc, XIIa–XIIc, XIIIa–
XIIIc, XIVa–XIVc, XVIIa, and XXV.
3.04 t (2H, CH2, J = 7.5 Hz), 4.92–5.05 m (6H, CH),
18.33 s (1H, OH). Found, %: C 77.38; H 9.74.
C24H36O3. Calculated, %: C 77.31; H 9.68.
2-[(9Z)-Octadec-9-enoyl]cyclohexane-1,3-dione
(XIa). Yield 66 (a), 87 (b), 99% (c). IR spectrum, ν,
5,5-Dimethyl-2-[(9Z,12Z,15Z)-octadeca-9,12,15-
trienoyl]cyclohexane-1,3-dione (XIIIc). Yield 83%
(b). IR spectrum, ν, cm–1: 1675 (C=O), 1575 (C=O,
chelated). 1H NMR spectrum, δ, ppm: 0.98 t (3H, CH3,
J = 7.0 Hz), 1.08 s (6H, CH3), 1.34 br.s (12H, CH2),
1.60–1.61 m (2H, CH2), 2.02–2.08 m (4H, CH2), 2.35 s
(2H, CH2), 2.53 s (2H, CH2), 3.02 t (2H, CH2, J =
7.5 Hz), 5.28–5.37 m (6H, CH), 18.27 s (1H, OH).
Found, %: C 77.95; H 10.06. C26H40O3. Calculated, %:
C 77.88; H 10.16.
1
cm–1: 1670 (C=O), 1565 (C=O, chelated). H NMR
spectrum, δ, ppm: 0.90 t (3H, CH3, J = 6.5 Hz),
1.30 br.s (20H, CH2), 1.65–1.68 m (2H, CH2), 1.67–
2.05 m (4H, CH2), 2.07–2.09 m (2H, CH2), 2.33 t (2H,
CH2, J = 7.0 Hz), 2.50 t (2H, CH2, J = 7.0 Hz), 3.03 t
(2H, CH2, J = 7.5 Hz), 5.31–5.33 m (2H, CH), 18.28 s
(1H, OH). Found, %: C 76.55; H 10.71. C24H40O3. Cal-
culated, %: C 76.52; H 10.74.
5-Methyl-2-[(9Z)-octadec-9-enoyl]cyclohexane-
1,3-dione (XIb). Yield 89 (b), 99% (c). IR spectrum, ν,
2-(Undec-10-enoyl)cyclohexane-1,3-dione
1
cm–1: 1670 (C=O), 1560 (C=O, chelated). H NMR
(XIVa). Yield 100% (b). IR spectrum, ν, cm–1: 1670
spectrum, δ, ppm: 0.88 t (3H, CH3, J = 6.5 Hz), 1.07 d
(3H, CH3, J = 6.5 Hz), 1.26 br.s (20H, CH2), 1.58–
1.62 m (2H, CH2), 1.92–1.96 m (4H, CH2), 2.09–
2.11 m (1H, CH), 2.22–2.28 m (2H, CH2), 2.57–
2.59 m (2H, CH2), 2.90 t (2H, CH2, J = 7.5 Hz), 5.21–
5.23 m (2H, CH), 18.85 s (1H, OH). Found, %:
C 76.87; H 10.84. C25H42O3. Calculated, %: C 76.84;
H 10.86.
1
(C=O), 1560 (C=O, chelated). H NMR spectrum, δ,
ppm: 1.36 br.s (10H, CH2), 1.65–1.68 m (2H, CH2),
2.04–2.08 m (2H, CH2), 2.51 t (2H, CH2, J = 7.0 Hz),
2.68 t (2H, CH2, J = 7.0 Hz), 2.71–2.74 m (2H, CH2),
3.04 t (2H, CH2, J = 7.5 Hz), 4.92 d.d (2H, CH2, J =
17.0, 28.0 Hz), 5.81–5.84 m (1H, CH), 18.33 s (1H,
OH). Found, %: C 73.34; H 9.41. C17H26O3. Calculat-
ed, %: C 73.31; H 9.38.
5,5-Dimethyl-2-[(9Z)-octadec-9-enoyl]cyclo-
hexane-1,3-dione (XIc). Yield 70 (b), 99% (c). IR
spectrum, ν, cm–1: 1670 (C=O), 1565 (C=O, chelated).
1H NMR spectrum, δ, ppm: 0.90 t (3H, CH3, J =
6.5 Hz), 1.10 s (6H, CH3), 1.25 br.s (20H, CH2), 1.58–
1.60 m (2H, CH2), 1.98–2.02 m (4H, CH2), 2.33 s (2H,
CH2), 2.45 s (2H, CH2), 3.02 (2H, CH2, J = 7.5 Hz),
5.00–5.02 m (2H, CH), 18.24 s (1H, OH). Found, %:
C 77.18; H 10.96. C26H44O3. Calculated, %: C 77.16;
H 10.92.
5,5-Dimethyl-2-(undec-10-enoyl)cyclohexane-
1,3-dione (XIVc). Yield 100% (b). IR spectrum, ν,
1
cm–1: 1670 (C=O), 1560 (C=O, chelated). H NMR
spectrum, δ, ppm: 1.12 s (6H, CH3), 1.34 br.s (10H,
CH2), 1.63–1.68 m (2H, CH2), 2.01–2.04 m (2H, CH2),
2.38 s (2H, CH2), 2.56 s (2H, CH2), 3.05 t (2H, CH2,
J = 7.5 Hz), 4.95 d.d (2H, CH2, J = 17.0, 28.0 Hz),
5.80–5.84 m (1H, CH), 18.30 s (1H, OH). Found, %:
C 74.47; H 9.87. C19H30O3. Calculated, %: C 74.41;
H 9.84.
2-[(9Z,12Z)-Octadeca-9,12-dienoyl]cyclohexane-
1,3-dione (XIIa). Yield 100% (b). IR spectrum, ν,
2-[(9E)-Octadec-9-enoyl]cyclohexane-1,3-dione
(XVIIa). Yield 100% (b). IR spectrum, ν, cm–1: 1670
1
cm–1: 1670 (C=O), 1560 (C=O, chelated). H NMR
1
(C=O), 1560 (C=O, chelated). H NMR spectrum, δ,
spectrum, δ, ppm: 0.91 t (3H, CH3, J = 6.5 Hz),
1.30 br.s (14H, CH2), 1.65–1.68 m (2H, CH2), 1.97–
2.07 m (6H, CH2), 2.50 t (2H, CH2, J = 7.0 Hz), 2.66 t
(2H, CH2, J = 7.0 Hz), 2.76 t (2H, CH2, J = 7.0 Hz),
3.02 t (2H, CH2, J = 7.5 Hz), 5.29–5.36 m (4H, CH),
18.28 s (1H, OH). Found, %: C 76.96; H 10.23.
C24H38O3. Calculated, %: C 76.94; H 10.11.
ppm: 0.90 t (3H, CH3, J = 6.5 Hz), 1.20 br.s (20H,
CH2), 1.60–1.62 m (2H, CH2), 1.97–2.07 m (6H, CH2),
2.48 t (2H, CH2, J = 7.0 Hz), 2.65 t (2H, CH2, J =
7.0 Hz), 3.01 t (2H, CH2, J = 7.5 Hz), 5.34–5.38 m
(2H, CH), 18.27 s (1H, OH). Found, %: C 76.55;
H 10.71. C24H40O3. Calculated, %: C 76.45; H 10.70.
2-[(9Z,12Z,15Z)-Octadeca-9,12,15-trienoyl]-
cyclohexane-1,3-dione (XIIIa). Yield 87% (b). IR
spectrum, ν, cm–1: 1675 (C=O), 1570 (C=O, chelated).
1H NMR spectrum, δ, ppm: 0.98 t (3H, CH3, J =
7.0 Hz), 1.32 br.s (12H, CH2), 1.58–1.61 m (2H, CH2),
2.06–2.08 m (4H, CH2), 2.41 t (2H, CH2, J = 6.5 Hz),
2.49–2.51 m (2H, CH2), 2.68 t (2H, CH2, J = 7.0 Hz),
Methyl 2,2-dimethyl-5-[(9Z)-octadec-9-enoyl]-
4,6-dioxocyclohexane-1-carboxylate (XXV). Yield
75% (b). IR spectrum, ν, cm–1: 1670 (C=O), 1565
1
(C=O, chelated). H NMR spectrum, δ, ppm: 0.88 t
(3H, CH3, J = 6.5 Hz), 1.08 s and 1.12 s (6H, CH3),
1.30 br.s (20H, CH2), 1.64–1.68 m (2H, CH2), 1.98–
2.02 m (4H, CH2), 2.41 s and 2.46 s (2H, CH2), 3.00 t
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 10 2008

LAKHVICH et al.
1450
5. Mudd, A., J. Chem. Soc., Chem. Commun., 1978,
(2H, CH2, J = 7.5 Hz), 3.26 s and 3.30 s (1H, CH),
3.73 s and 3.75 s (3H, CH3), 5.30–5.35 m (2H, CH),
18.17 s and 18.24 s (1H, OH). Found, %: C 72.69;
H 10.02. C28H46O5. Calculated, %: C 72.60; H 10.14.
p. 1075.
6. Kato, M.J., Lopes, L.M.X., Fo, H.F.P., Yoshida, M., and
Gottlieb, O.R., Phytochemistry, 1985, vol. 24, p. 533.
7. Mudd, A., J. Chem. Soc., Perkin Trans. 1, 1981,
p. 2357.
REFERENCES
8. Akhrem, A.A., Lakhvich, F.A., Budai, S.I., Khlebni-
cova, T.S., and Petrusevich, I.I., Synthesis, 1978, p. 925.
9. Lakhvich, F.A., Petrusevich, I.I., and Sergeeva, A.N.,
1. Lakhvich, F.A. and Khlebnikova, T.S., Vestsi Nats. Akad.
Navuk Belarusi, Ser. Khim., 1996, no. 4, p. 101.
Russ. J. Org. Chem., 1995, vol. 31, p. 1473.
10. Oliver, J.E., Synthesis, 1990, p. 1117.
2. Rubinov, D.B., Rubinova, I.L., and Akhrem, A.A., Khim.
Prirodn. Soedin., 1995, p. 635.
3. Oliver, J.E., Lusby, W.R., and Neal, J.W., J. Chem. Ecol.,
11. Zaitsev, V.G., Polozov, G.I., and Lakhvich, F.A., Tetra-
hedron, 1994, vol. 50, p. 6377.
1990, vol. 16, p. 2243.
4. Corbet, S.A., Nature, 1971, vol. 232, p. 481.
12. Mudd, A., J. Chem. Ecol., 1985, vol. 11, p. 51.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 10 2008