Acid-catalyzed isomerization of caryophyllene in the presence of SiO2 and Al2O3 impregnated with sulfuric acid

Article abstract of DOI:10.1007/s11172-018-2179-3

The conversion of caryophyllene upon contact with Al₂O₃ and SiO₂ impregnated with sulfuric acid was carried out, and the components of the resulting mixtures were identified. Having in hands such “standard” mixtures greatl

Full text of DOI:10.1007/s11172-018-2179-3

Russian Chemical Bulletin, International Edition, Vol. 67, No. 6, pp. 1051—1058, June, 2018
1051
Acid-catalyzed isomerization of caryophyllene
in the presence of SiO2 and Al2O3 impregnated with sulfuric acid
E. P. Romanenko and A. V. Tkachev
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences,
9 prosp. Akad. Lavrent´eva, 630090 Novosibirsk, Russian Federation.
Fax: +7 (383) 330 9752. E-mail: atkachev@nioch.nsc.ru
The conversion of caryophyllene upon contact with Al2O3 and SiO2 impregnated with
sulfuric acid was carried out, and the components of the resulting mixtures were identified.
Having in hands such "standard" mixtures greatly facilitates identification of components of
sesquiterpene fractions of essential oils and other mixtures of natural origin. The catalytic activ-
ity of silica gel impregnated with sulfuric acid (H+-SiO2) in the acid-catalyzed isomerization
of caryophyllene is significantly higher than that for H+-Al2O3 and is comparable with the
activity of concentrated sulfuric acid.
Key words: sesquiterpenoids, caryophyllene, isomerization, acid catalysis.
Sesquiterpenoids are a very important group of plant
metabolites. Although the content of these compounds in
natural sources is often low, they play a very impor-
tant biological role. Among them, caryophyllene, i.e.,
1R,4E,9S-4,11,11-trimethyl-8-methylidenebicyclo[7.2.0]-
undec-4-ene (1), takes a special place.1—8 One of the
barriers to practical application of sesquiterpenoids is the
insufficient knowledge of their metabolic characteristics.9
This kind of studies is restrained, in particular, by the lack of
simple methods for the obtaining the "standard" mixtures
containing various caryophyllene derivatives. The need for
these mixtures is substantiated by the fact that sesquiter-
penoids, because of the variety of their structures, close
retention parameters, and similar mass spectra,10 represent
the group of compounds most complicated for analysis.
In the present work, we describe access to the mixtures
of caryophyllene compounds using acid-catalyzed conver-
sions in the presence of Al2O3 and SiO2 impregnated with
sulfuric acid. A determining factor influencing the reaction
course with these catalysts can be not only the concentra-
tion of the reagents on the surface of the adsorbent, but
also the nature of the latter. Reactions in the presence of
SiO2 and Al2O3 often proceed under mild conditions, they
are characterized by higher chemo-, regio- and stereo-
selectivity of transformations and simple procedures for
isolation of products in comparison with similar homo-
geneous reactions.11—15
from 1 to 20 wt.%. The following samples of catalysts
were obtained: H+-Al2O3(5%), H+-Al2O3(20%), H+-SiO2
(1%)
and H+-SiO2(5%). The isomerization of caryophyllene 1
was carried out by reacting its solution in hexane with the
acid impregnated sorbent at 20 or 68 °C; the contact time
of the substrate solution with the catalyst ranged from
1—5 min to 72 h. The individual components were isolated
from the product mixtures by a combination of column
chromatography on SiO2 or AgNO3/SiO2 and preparative
gas chromatography.
The acid-impregnated alumina H+-Al2O3 has a low
activity with respect to caryophyllene 1 (Table 1, en-
tries 1—8): when the catalyst with a 5% acid content (H+-
Al2O3(5%)) was used, the conversion of caryophyllene 1
after 24 h at 20 °C did not exceed 10% (entry 1). A complete
conversion was reached after increasing the reaction tem-
perature (entry 4), with a mixture of six alcohols (2—7)
and eleven hydrocarbons (8—16) being formed. The struc-
tures of caryolan-1-ol (2),16—18 isocaryolan-8-ol (3),16
clovan-2β-ol (4),19,20 caryophyllen-8β-ol (5),21 caryo-
phyllen-4β-ol (6),22 isocaryophyllene (8),19,23 isomeric
dienes 9, 10,23 clovene (11),19,24 3,8-cyclocaryophyll-4-
ene (12),19 isomeric 5,8-cyclocaryophyllenes 13, 14,19
Δ
8,9-isocaryolane (15),23 and α-neoclovene (16)19 were
established based on the comparison of their mass spectra
and linear retention indices with those described in the
work.25 The structure of ginsenol (7) was established by
the comparison of its NMR spectra with the spectra de-
scribed in the literature.26
Results and Discussion
Analysis of scientific literature devoted to the study of
acid-catalyzed transformations of mono-, sesqui- and
diterpenoids shows that the formation of final products is
explained by the following processes: (1) intramolecular
The catalysts were prepared by impregnation of the
sorbent (Al2O3 or SiO2) with an aqueous solution of H2SO4
and subsequent removal of water; the acid content ranged
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1051—1058, June, 2018.
1066-5285/18/6706-1051 © 2018 Springer Science+Business Media, Inc.

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Romanenko and Tkachev

Acid-catalyzed isomerization of caryophyllene
Russ. Chem. Bull., Int. Ed., Vol. 67, No. 6, June, 2018
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Romanenko and Tkachev
cyclizations of unsaturated compounds; (2) rearrange-
ments caused by migration of a hydride ion and/or alkyl
groups; (3) reactions involving water (formation of alcohols
from the corresponding carbocations); (4) intermolecular
reactions of a hydride ion addition to carbocations to form
saturated compounds (the reaction medium components
may serve as sources of hydride ions); (5) intermolecular
reactions of proton elimination from the allylic-type carbo-
cations to form dienes (other compounds present in the
reaction medium may act as proton acceptors).
The first stage of the reaction of caryophyllene 1 with
the acid catalyst is the competitive protonation of endo-
and exocyclic double bonds (Scheme 1). Subsequent de-
protonation (or several successive protonation-deproton-
ation steps) of carbocations A and B leads to a mixture of
dienes 8—10, while the addition of water gives alcohols 5
and 6. These reactions are reversible, and the accumulation
of these products is observed only at low conversion. In
addition, dienes 9 and 10 can be irreversibly consumed in
the intramolecular carbocyclization leading to tricyclic
olefins 12 and 16. The cyclization of carbocation B gives
two isomeric tricyclic alkenes 13 and 14. The results pre-
sented in Table 1 indicate the reversibility of the formation
of these products.
In the thermodynamically controlled reaction, carbo-
cation A also undergoes carbocyclization, which, depend-
ing on the carbocation conformation, results in caryolan-
1-ol 2 or clovene 11 as the major products (the content
of caryolan-1-ol 2 in the product mixture can reach
50%). Apart from that, carbocation A through the inter-
mediate diene bearing two exocyclic bonds can un-
dergo ring closure to isocaryolan-8-ol 3, with no inter-
mediate diene being detected in the mixture in appre-
ciable amounts.
mixture with the catalyst H+-SiO2 is long or when the
reaction is carried out at an elevated temperature (en-
tries 16, 17), compounds 17—21 become the predominant
reaction products.
The structure of compounds 1727 and 1824 was estab-
lished based on the comparison of their NMR spectra with
the spectra described in the literature. The structure of
isocaryolane 19 was established based on the NMR spec-
troscopy data and confirmed by the synthesis of an authen-
tic sample by the reduction of isocaryolan-9-one (22) with
hydrazine.28
Neoclovane 20 is one of the isomeric products of the
catalytic hydrogenation of α-neoclovene. In the synthesis
of neoclovane by reduction of two stereoisomeric ketones
25 and 26 with the N2H4/KOH system, only isomer 27
is formed. This occurs due to the epimerization of ke-
tones in the alkaline medium to form a more stable ke-
tone 25 with trans-arrangement of the methyl groups
(Scheme 2).
The structure of tricyclic saturated sesquiterpenoid 21
was inferred from the NMR spectroscopy data. The forma-
tion of this compound can be ascertained by Scheme 3.
The four-membered ring expansion in the cation with
the caryolane skeleton C to the five-membered ring
of the epiclovane skeleton G with subsequent expan-
sion of one of its six-membered rings leads to the forma-
tion of tricyclo[5.3.2.04,11]dodecane core H. A series
of several sequential 1,2-shifts of hydrogen and a methyl
group in the latter leads to carbocation I, which is an di-
rect precursor of tricycloalkane 21. Carbocations H
and I, as well as the products of their reactions with
nucleophiles, were described previously in the work17
studied the behavior of 1-substituted caryolanes in super-
acidic media.
The general regularities of the reaction carried out in
the presence of H+-Al2O3 (see Table 1, entries 1—8) cor-
respond to those observed in the homogeneous version of
the reaction in the H2SO4—diethyl ether or H2SO4—ace-
tone (entries 9—12).
The precursor of tricyclic diene 17 is carbocation D
with a clovane framework. A series of several successive
1,2-shifts of hydrogen and a methyl group and abstraction
of the hydride ion from the intermediately formed olefin
lead to allylic ion J, the direct precursor of compound 1724
(Scheme 4).
In addition to cation I, the carbocations with the
caryolane (C), isocaryolane (E), and neoclovane (F) cores
(precursors of compounds 18—20) act as the hydride ion
acceptors (see Scheme 1).
The activity of the acid impregnated silica gel H+-SiO2
in the reaction with caryophyllene 1 (see Table 1, en-
tries 13—17) is significantly higher than that of H+-Al2O3:
the starting caryophyllene 1 was detected only in the ex-
periments using the catalyst with a low acid content
H+-SiO2
(entries 13 and 14). The set of reaction
The higher catalytic activity of H+-SiO2 as compared
to H+-Al2O3 has already been noted in the literature on
the example of sorbents impregnated with phosphoric29
or phosphotungstic acid.30 Apparently, this is explained
by a weaker interaction of the impregnated acid with the
surface of silica gel than with the surface of alumina.31,32
In addition, a partial solubility of the substrate upon im-
pregnation with a strong mineral acid considerably con-
tributes to the lowering of the activity of H+-Al2O3. For
example, when 5% sulfuric acid is used to prepare the
catalyst, up to 45% of the impregnated acid is consumed
(1%)
products obtained with H+-SiO2(1%) does not fundamen-
tally differ from that obtained with H+-Al2O3.
On going to the catalyst with higher acid content
H+-SiO2
(see Table 1, entries 15—17), new compo-
(5%)
nents appear in the reaction products: tricyclic diene
(1R,8R)-3,4,8-trimethyltricyclo[6.3.1.01,5]dodeca-3,5-
diene (17) and four saturated tricyclic sesquiterpenoids,
caryolane (18), isocaryolane (19), neoclovane (20), and
(1R,3R,4S,7S,11S)-3,7,11-trimethyltricyclo[5.3.2.04,11]-
dodecane (21). When the contact time of the reaction

Acid-catalyzed isomerization of caryophyllene
Russ. Chem. Bull., Int. Ed., Vol. 67, No. 6, June, 2018
1055
Scheme 2
Reagents and conditions: i. H2, Pd/C, EtOAc; ii. 1) BF3•Et2O, LiAlH4; 2) H2O2, NaOH; iii. CrO3, HOAc, H2O; iv. N2H4•H2O,
KOH, triethylene glycol.
to dissolve Al2O3, so that the actual amount of the acid
on the sorbent surface is less than 3 wt.%.
The composition of the reaction mixture obtained by
the isomerization of caryophyllene 1 in the two-phase
system H2SO4—hexane (see Table 1, entry 18) is qualita-
tively the same observed for the H+-SiO2—hexane system
(entries 16, 17): after 3 h of reflux of the reaction mixture,
compounds 17, 18, and 21 are the predominant compo-
nents. A similar behavior in the studied reaction of H2SO4
and H+-SiO2 confirms the literature data14,15 on the com-
mensurability of the catalytic activity of concentrated
sulfuric acid and H+-SiO2.
Scheme 3

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Russ. Chem. Bull., Int. Ed., Vol. 67, No. 6, June, 2018
Romanenko and Tkachev
Scheme 4
N-AW-DMCS or 15% Carbowax 600/Chromaton N-AW-DMCS
column, 4.5 m×1.6 mm, carrier gas nitrogen at a flow rate of
60 mL min–1, column temperature of 150—200 °C.
Analytical TLC was performed on Sorbfil pre-coated plates;
the spots were visualized by spraying the plates with an ethanolic
solution of vanillin (0.5 g of vanillin and 5 mL of concentrated
H2SO4 in 100 mL of EtOH).
Experimental
(–)-Caryophyllene 1 with a parameter [α]15
–9.78 was
578
obtained by rectification in vacuo of the nonphenolic fraction of
clove oil. To prepare sorbents impregnated with sulfuric acid, TU
6-09-3916-75 alumina and KSK silica gel with the particle size
of 0.002-0.040 mm were used. All solvents were used freshly
distilled.
Preparation of H+-Al2O3 catalysts (general procedure). The
H+-Al2O3
catalyst with 5% content of acid was obtained by
(5%)
Reaction mixtures were analyzed by chromatography-mass
spectrometry using a Hewlett Packard G1081A instrument con-
sisting of an HP 5890 series II gas chromatograph and an HP MSD
5971 mass selective detector (70 eV); an HP5 column (5% of diphen-
yl- and 95% of dimethylsiloxane): 30 m×00.25 mm×0 0.25 μm;
carrier gas helium at a flow rate of 1 mL min–1; the column
temperature was programmed as follows: 2 min at 50 °C, tem-
perature increase at a rate of 10 deg min–1, 5 min at 280 °C;
temperature of ion source was 173 °C. Data were collected at
a rate of 1.2 scan s–1 in the mass range of 30—650 a.m.u. A mixture
of normal hydrocarbons C8—C24 was added to the test samples
as a standard for determining linear retention indices. The iden-
tification of the mixture components was based on a comparison
of their mass spectra and retention indices with the correspond-
ing data for the reference compounds. The content of the com-
ponents in the mixture was calculated by the peak areas without
correction coefficients.
NMR spectra were recorded on a Bruker DRX-500 spectro-
meter (500.132 (1H) and 125.758 МHz (13C)) at 25 °C in CDCl3
or in a mixture of CDCl3—CCl4 (1 : 1) using a sample concentra-
tions of 25—50 mg mL–1. Residual signals of the solvents were
used as a reference: δH 7.24 (CHCl3) and δC 76.90 (CDCl3).
Signals were assigned using 13С NMR spectra recorded in
a J-modulation mode and the following 2D spectra: (1) 1H—1H
homonuclear correlation, (2) 13C—1H hetеrоnuclear correlation
on direct spin-spin coupling constants (J = 135 Hz), and (3)
13C—1H hetеrоnuclear correlation on indirect spin-spin coupling
constants (J = 10 Hz).
the addition of 5% aqueous H2SO4 (10.0 g) to Al2O3 (10.0 g).
The mixture was stirred at room temperature for 30 min. Water
was evaporated on a rotary evaporator. The resulting catalyst was
dried at 130 °C for 10 h. The H+-Al2O3
catalyst with 20%
(20%)
content of acid was prepared similarly using 20% aq. H2SO4.
Preparation of H+-SiO2 catalysts (general procedure). The
H+-SiO2
catalyst with 5% content of acid was obtained by
(5%)
the addition of 2.5% aq. H2SO4 (20.0 g) to SiO2 (10.0 g). The
mixture was stirred at room temperature for 30 min. Water was
evaporated on a rotary evaporator. The resulting catalyst was
dried at 130 °C for 10 h. The H+-SiO2(1%) catalyst with 1% con-
tent of acid was prepared similarly using 0.5% aq. H2SO4.
Isomerization of caryophyllene (1) on H+-Al2O3 or H+-SiO2
(general procedure). A solution of caryophyllene 1 (25.0 mg,
0.122 mmol) in hexane (0.8 mL) was applied to a chromato-
graphic column (5 mm in diameter) containing H+-Al2O3 or
H+-SiO2 (0.50 g). After standing at 20 °C for a control time, the
column was washed with hexane (5 mL) and EtOAc (5 mL) (in
the case of H+-Al2O3) or acetone (5 mL) (in the case of H+-SiO2).
The experiments in which the contact time of the solution of
compound 1 with the catalyst was over 24 h, as well as the ex-
periments at elevated temperature, were carried out in a flat-
bottom flask with stirring (the solvent volume 2.5 mL). The results
of the experiments are presented in Table 1.
The isomerization of caryophyllene 1 in the H2SO4—acetone
(H2SO4—diethyl ether) system was carried out similarly to the
described procedure.19
Isomerization of caryophyllene (1) in the H2SO4—hexane
system (general procedure). Sulfuric acid (0.5 mL, 9.33 mmol)
was added to a solution of caryophyllene 1 (50.0 mg, 0.245 mmol)
in hexane (2 mL). The mixture was refluxed with vigorous stirring
for 3 h. The organic solution was separated, the residue was di-
luted with water (2 mL), extracted with hexane (3×1 mL) and
diethyl ether (3×1 mL). The combined organic fractions were
washed with water and dried with MgSO4.
Optical rotation angles were measured on a Polamat A po-
larimeter at λ = 578 nm.
Components of the mixtures were separated by (1) column
chromatography on KSK silica gel with a particle size of
0.140—0.315 mm activated at 130 °C for 6 h, (2) column chrom-
atography on silica gel impregnated with 10% AgNO3, and (3)
preparative gas chromatography on a 15% OV-101/Chromaton

Acid-catalyzed isomerization of caryophyllene
Russ. Chem. Bull., Int. Ed., Vol. 67, No. 6, June, 2018
1057
Isocaryolane (19). A mixture of isocaryolan-9-one 22 (54 mg,
0.24 mmol) obtained by isomerization of caryophyllene oxide
on H+-SiO2,33 hydrazine hydrate (250 μL, 5.14 mmol), and
КОН (100 mg, 1.78 mmol) in triethylene glycol (2 mL) was
refluxed at 130 °C for 1 h. Then, water and excessive hydrazine
hydrate were evaporated. The residue was heated at 180—190 °C
for 5 h. The reaction mixture was diluted with water (3 mL),
extracted with hexane (4×2 mL), the combined extracts were
washed with water (3×1 mL) and dried with MgSO4. A light
yellow oil (34 mg) was obtained after evaporation of the solvent.
Purification by column chromatography (SiO2, eluent hexane)
gave isocaryolane 19 (26 mg) as a colorless oil. 1H NMR
(CDCl3—CCl4 (1 : 1)), δ: 0.74 (s, 3 H, C(15)H3); 0.96 (s, 3 H,
C(14)H3); 0.98 (s, 3 H, C(13)H3); 1.61 (m, 1 H, H(5)); 1.98
(m, 1 H, H(8)); 2.05 (dt, 1 H, H(2), J = 11.4 Hz, J = 8.0 Hz).
13C NMR (CDCl3—CCl4 (1 : 1)), δ: 19.7 (t, C(10)); 20.9
(q, C(13)); 26.0 (t, C(6)); 27.9 (q, C(15)); 30.1 (t); 30.8 (q, C(14));
31.4 (s, C(1)); 32.2 (d, C(8)); 32.9 (t); 34.0 (s, C(4)); 36.7
(t, C(3)); 39.6 (t); 41.5 (t); 41.8 (d, C(2)); 47.6 (d, C(5)).
α-Neoclovene (16). A solution of isocaryophyllene 8 (1.0 g,
4.9 mmol) in diethyl ether (5 mL) was added dropwise to a solu-
tion of H2SO4 (5.0 g) in diethyl ether cooled to 0 °C with vigor-
ous stirring. The reaction mixture was maintained at this tem-
perature for 1 h and neutralized with 15% aq. NaOH. The or-
ganic layer was separated, the aqueous layer was extracted with
diethyl ether (4×5 mL), the combined organic fractions were
washed with water (3×5 mL) and dried with anhydrous MgSO4.
Evaporation of the solvent gave 1.0 g of a residue. The hydro-
carbon fraction (652 mg) was separated from the mixture by
column chromatography (SiO2, eluent hexane, then EtOAc).
α-Neoclovene 16 (235 mg) was separated from the mixture of
hydrocarbons by preparative gas chromatography (a 15% OV-101/
Chromaton N-AW-DMCS column, column temperature 150 °C).
Reduction of α-neoclovene (16) with hydrogen was carried out
according to the procedure described in the work,34 which re-
sulted in a mixture of two isomeric neoclovanes with the linear
retention indexes of 1464 and 1482. The mass spectra of the
neoclovanes obtained agree with those described earlier.35
Hydroboration—oxidation of α-neoclovene (16). To a stirred
solution of α-neoclovene 16 (100 mg, 0.29 mmol) in anhydrous
diethyl ether (6 mL) cooled to 0 °C, BF3•Et2O (100 μL,
0.81 mmol) was added followed by addition of LiAlH4 (40 mg,
1.05 mmol) in small portions. The mixture was kept at this tem-
perature for 2 h, followed by addition of 3 М aq. NaOH (0.8 mL)
and H2O2 (0.1 mL, 0.98 mmol) and stirring at 20 °C for 3 h.
The organic layer was separated, washed with saturated aq. FeSO4
(1 mL), 0.5 М aq. HCl (1 mL), and water (2×1 mL), dried with
anhydrous MgSO4. Evaporation of the solvent gave 94 mg of
a mixture of alcohols as a colorless oil. The mixture of alcohols
was separated by column chromatography (SiO2, gradient elution
with a mixture of hexane—CH2Cl2 (100 : 0→0 : 100)) to obtain
alcohol 23 (39.5 mg, 36%) and alcohol 24 (18.8 mg, 17%) (m.p.
140—142 °C). The NMR spectra of these alcohols agree with
those described in the literature.34
MgSO4. Ketone 25 (28 mg, 91%) was obtained after evaporation
of the solvent.
Ketone 26 (15.0 mg, 82%) was obtained similarly from alco-
hol 24 (18.5 mg).
(1R,2S,6S,7S)-2,6,8,8-Tetramethyltricyclo[5.2.2.01,6]undec-
ane (27), neoclovane. A mixture of ketone 25 (10.5 mg, 0.05 mmol),
N2H4•H2O (50 μL, 1.03 mmol), KOH (40 mg, 0.71 mmol), and
triethylene glycol was heated at 180—190 °C for 4 h. After cool-
ing, the mixture was diluted with water (2 mL) and extracted with
hexane (6×1 mL). The combined extracts were washed with
water (3×1 mL) and dried with anhydrous MgSO4. Tricycloalkane
27 (6.0 mg, 61%) was obtained after evaporation of the solvent.
1H NMR (CDCl3), δ: 0.71 (d, С(12)H3, J12,2 = 6.8 Hz); 0.99
(s, С(14)H3); 1.03 (s, С(13)H3); 1.12 (d, H(9), J9,9´ = 12.0 Hz);
1.16 (s, С(15)H3); 1.40 (dd, H(9´), J9´,9 = 12.0 Hz, J9´,10 = 3.3 Hz);
1.44 (ddq, H(2), J2,3α = 4.8 Hz, J2,3β = 11.5 Hz, J1,12 = 6.8 Hz).
13C NMR (CDCl3), δ: 17.8 (q, C(12)); 18.7 (q, C(13)); 21.4
(t, C(11)); 22.0 (t, C(4)); 25.4 (t, C(10)); 29.5 (t, C(3)); 29.8
(t, C(5)); 31.7 (q, C(14)); 31.8 (q, C(15)); 32.2 (d, C(2)); 36.4
(s, C(8)); 49.7 (s, C(6)); 50.3 (t, C(9)); 51.5 (s, C(1)); 55.5
(d, C(7)). МS, m/z (Irel (%)): 206 [M]+ (25), 191 (58), 178 (13),
177 (10), 164 (13), 163 (84), 151 (20), 150 (73), 149 (20), 136
(20), 135 (52), 124 (37), 123 (53), 122 (43), 121 (47), 110 (17),
109 (86), 108 (33), 107 (79), 105 (14), 97 (17), 96 (26), 95 (63),
94 (84), 93 (65), 91 (35), 83 (16), 82 (70), 81 (100), 80 (15), 79
(44), 77 (27), 69 (51), 67 (45), 65 (10), 55 (46), 53 (18), 43 (13),
41 (55), 39 (16).
Neoclovane 27 (8.8 mg, 65%) was obtained by the reduction
of ketone 26 (14.5 mg) by a similar procedure.
(1R,3R,4S,7S,11S)-3,7,11-Trimethyltricyclo[5.3.2.04,11]-
dodecane (21). [α]14578 –6.18 (c 4.85, CCl4). 1H NMR (CDCl3),
δ: 0.81 (d, С(13)H3, J13,3 = 6.8 Hz); 0.83 (s, C(15)H3); 0.91
(s, C(14)H3); 2.32 (ddddd, H(1), J = 3.0 Hz, J = 4.8 Hz,
J = 9.1 Hz, J = 9.1 Hz, J = 11.9 Hz). 13C NMR (CDCl3), δ: 12.4
(q, C(13)); 23.0 (t, C(9)); 23.9 (q, C(14)); 26.4 (t, C(5)); 31.2
(t, C(10)); 33.3 (s, C(7)); 35.1 (t, C(12)); 35.2 (t, C(6)); 35.9
(q, C(15)); 36.7 (t, C(2)); 37.4 (d, C(1)); 40.1 (s, C(4)); 44.3
(d, C(3)); 44.8 (t, C(8)); 47.4 (d, C(11)). МS, m/z (Irel (%)): 206
(48), 192 (15), 191 (97), 177 (16), 164 (25), 163 (80), 150 (10),
149 (31), 137 (20), 136 (12), 135 (39), 123 (13), 122 (16), 121 (47),
120 (5), 119 (5), 111 (10), 110 (11), 109 (71), 108 (31), 107 (70),
106 (7), 105 (8), 97 (7), 96 (33), 95 (95), 94 (17), 93 (55), 92 (9),
91 (32), 83 (13), 82 (22), 81 (70), 80 (11), 79 (36), 78 (8), 77 (28),
69 (35), 68 (24), 67 (64), 65 (12), 57 (9), 56 (5), 55 (68), 54 (5),
53 (29), 51 (5), 43 (24), 42 (8), 41 (100), 40 (8), 39 (29), 32 (19).
Evaluation of the solubility of the sorbent during the prepara-
tion of the catalyst. A freshly prepared H+-Al2O3
catalyst
(5%)
(2.5 g) was washed with water (10×10 ml) until neutral pH of the
washings was reached. The washings were concentrated in vacuo
to a volume of 50 mL. In the concentrate obtained, the concen-
tration of Al3+ was determined by a known procedure,36 as well
as the concentration of H+: C(Al3+) = 0.0075—0.0082 mol L–1
(which corresponds to the consumption of H2SO4 43—47%),
C(H2SO4) = 0.0135—0.0140 mol L–1 (52—54% from the theo-
retical). In a similar procedure with H+-SiO2(5%), no silicon
ions were detected in the solution, with С(H2SO4) = 0.0210—
0.0260 mol L–1 (80—100% from the theoretical).
The linear retention indices of caryophyllene (1) and its iso-
merization products 2—20 are as follows (in ascending order): 1360
(11), 1367 (13), 1371 (14), 1380 (12), 1408 (18), 1412 (8), 1415
(19), 1415 (15), 1422 (1), 1434 (10), 1451 (9), 1451 (16), 1455
Oxidation of alcohols 23 and 24. A solution of CrO3 (34 mg,
0.34 mmol) in a mixture of AcOH (200 μL) and water (100 μL)
was added dropwise to a solution of alcohol 23 (31 mg, 0.14 mmol)
in AcOH (1.7 mL). The mixture was maintained at 16 °C for
10 h, diluted with water (1.5 mL), and extracted with hexane
(6×1.5 mL). The combined extracts were washed with aq.
NaHCO3 (4×1 mL) and water (3×1 mL), dried with anhydrous

1058
Russ. Chem. Bull., Int. Ed., Vol. 67, No. 6, June, 2018
Romanenko and Tkachev
(17), 1482 (20), 1576 (2), 1581 (5), 1583 (3), 1605 (6), 1630 (7),
1635 (4).
19. L. Fitjer, A. Malich, C. Paschke, S. Kluge, R. Gerke,
B. Rissom, J. Weiser, M. Noltemeyer, J. Am. Chem. Soc.,
1995, 117, 9180.
20. K. Tanaka, Y. Matsubara, Nippon Kagaku Kaishi, 1976, 1883.
21. S. Shankar, R. M. Coates, J. Org. Chem., 1998, 63, 9177.
22. A. V. Tkachev, Yu. V. Gatilov, I. K. Korobeinicheva, Zh. V.
Dubovenko, V. A. Pentegova, Chem. Nat. Compd., 1983,
19, 154.
23. T. M. Homenko, D. V. Korchagina, Yu. V. Gatilov, I. Yu.
Bagryanskaya, A. V. Tkachev, A. I. Vjalkov, O. B. Kun, V. L.
Salenko, Zh. V. Dubovenko, V. A. Barkhash, J. Org. Chem.
USSR, 1990, 26, 1839.
References
1. A. V. Tkachev, Chem. Nat. Compd. (Engl.Transl.), 1987,
23, 393.
2. I. G. Collado, J. R. Hanson, A. J. Macias-Sanchez, Nat.
Prod. Rep., 1998, 15, 187.
3. M. G. Sarpietro, A. Di Sotto, M. L. Accolla, F. Castelli,
Thermochim. Acta, 2015, 600, 28.
4. R. Medeiros, G. F. Passos, C. E. Vitor, J. Koepp, T. L.
Mazzuco, L. F. Pianowski, M. M. Campos, J. B. Calixto,
Br. J. Pharmacol., 2007, 151, 618.
24. V. P. Gatilova, D. V. Korchagina, T. V. Rybalova, Yu. V.
Gatilov, Zh. V. Dubovenko, V. A. Barkhash, J. Org. Chem.
USSR, 1989, 25, 285.
5. L. Langhasova, V. Hanusova, J. Rezek, B. Stohanslova,
M. Ambroz, V. Kralova, T. Vanek, J. Dong Lou, Zh. Li Yun,
J. Yang, L. Skalova, Ind. Crops Prod., 2014, 59, 20.
6. A.-L. Klauke, I. Racz, B. Pradier, A. Markert, A. M. Zimmer,
J. Gertsch, A. Zimmer, Eur. Neuropsychopharmacol., 2014,
24, 608.
7. J. Gertsch, M. Leonti, S. Raduner, I. Racz, J.-Zh. Chen,
X.-Q. Xie, K.-H. Altmann, M. Karsak, A. Zimmer, Proc.
Natl. Acad. Sci. USA, 2008, 105, 9099.
8. G.-Q. Zheng, P. M. Kenney, L. K. Lam, J. Nat. Prod., 1992,
55, 999.
9. K. Fidyt, A. Fiedorowicz, L. Strządała, A. Szumny, Cancer
Med., 2016, 5, 3007.
10. W. A. König, N. Bülow, Y. Saritas, Flavour Fragrance J., 1999,
14, 367.
11. V. A. Basiuk, Russ. Chem. Rev., 1995, 64, 1003.
12. A. K. Banerjee, M. S. Laya, W. J. Vera, Russ. Chem. Rev.,
2001, 70, 971.
13. J. M. Riego, Z. Sedin, J. M. Zaldivar, N. C. Marziano,
C. Tortato, Tetrahedron Lett., 1996, 37, 513.
14. N. C. Marziano, C. Tortato, L. Ronchin, F. Martini, C. Bian-
chi, Catal. Lett., 1999, 58, 81.
15. N. C. Marziano, C. Tortato, L. Ronchin, C. Bianchi, Catal.
Lett., 2000, 64, 15.
25. A. V. Tkachev, Issledovaniye letuchikh veshchestv rasteniy
[Investigation of Volatile Substances of Plants], Offset, Novo-
sibirsk, 2008, 969 pp. (in Russian).
26. H. Iwabuchi, M. Yoshikura, W. Kamisako, Chem. Pharm.
Bull., 1988, 36, 2447.
27. G. A. Nisnevich, V. I. Makalskii, D. V. Korchagina, Yu. V.
Gatilov, I. Yu. Bagryanskaya, V. A. Barkhash, Russ. J. Org.
Chem., 1994, 30, 165.
28. I. G. Collado, J. R. Hanson, R. Hernandez-Galan, P. B.
Hitchcock, A. J. Macias-Sanchez, J. C. Racero, Tetrahedron,
1998, 54, 1615.
29. G. Ramis, P. F. Rossi, G. Busca, V. Lorenzelli, A. L. Ginestra,
P. Patrono, Langmuir, 1989, 5, 917.
30. L. R. Pizzio, C. V. Caceres, M. N. Blanco, Appl. Catal., A,
1998, 167, 283.
31. G. Busca, G. Ramis, V. Lorenzelli, P. F. Rossi, A. L. Ginestra,
P. Patrono, Langmuir, 1989, 5, 911.
32. C. M. Fougret, W. F. Holderich, Appl. Catal., A, 2001,
207, 295.
33. E. P. Romanenko, A. V. Tkachev, Chem. Sustain. Dev.,
2007, 571.
34. W. Parker, R. A. Raphael, J. S. Roberts, J. Chem. Soc. C,
1969, 2634.
35. K. Yoshihara, Y. Hirose, Bull. Chem. Soc. Jpn., 1975, 48, 2078.
36. G. Charlot, Les metodes de la chemie analytique: analyse
quantitative minrale, Masson etcie, Paris, 1961, 1024 p.
16. A. V. Tkachev, V. I. Mamatyuk, Zh. V. Dubovenko, J. Org.
Chem. USSR, 1990, 26, 1469.
17. V. P. Gatilova, D. V. Korchagina, I. Yu. Bagryanskaya,
Yu. V. Gatilov, Zh. V. Dubovenko, V. A. Barkhash, V. A.
Koptyug, J. Org. Chem. USSR, 1985, 21, 5.
18. V. Lamare, A. Archelas, R. Faure, M. Cesario, C. Pascard,
R. Furstoss, Tetrahedron, 1989, 45, 3761.
Received June 23, 2017;
in revised form December 5, 2017;
accepted December 27, 2017