Synthesis of Fencholenic Aldehyde from α-pinene Epoxide on Modified Clays

Article abstract of DOI:10.1007/s10600-018-2506-9

The conditions for isomerization of α-pinene epoxide (2,3-epoxypinane) on modified clays that gave comparatively high contents (33.0%) of fencholenic (iso-campholenic) aldehyde in the product mixture were determined. An effective method for isolating it w

Full text of DOI:10.1007/s10600-018-2506-9

DOI 10.1007/s10600-018-2506-9
Chemistry of Natural Compounds, Vol. 54, No. 5, September, 2018
SYNTHESIS OF FENCHOLENIC ALDEHYDE FROM α-PINENE
EPOXIDE ON MODIFIED CLAYS
1
1
1
A. Yu. Sidorenko, Zh. V. Ignatovich, A. L. Ermolinskaya,
1
2
1*
A. V. Kravtsova, A. V. Baranovskii, E. V. Koroleva,
and V. E. Agabekov
1
The conditions for isomerization of α-pinene epoxide (2,3-epoxypinane) on modified clays that gave
comparatively high contents (33.0%) of fencholenic (iso-campholenic) aldehyde in the product mixture were
determined. An effective method for isolating it was proposed. The structure of iso-campholenic aldehyde
was confirmed by analyzing 2D NOESY and HMBC NMR spectra.
Keywords: fencholenic aldehyde, campholenic aldehyde, isomerization, α-pinene epoxide.
Epoxides are accessible reactive compounds that are converted by Lewis and Bronsted acids into aldehydes, ketones,
or alcohols [1–3]. Thus, α-pinene epoxide (2,3-epoxypinane) is produced by chemical processing of turpentine and acts as a
source for trans-carveol [4], pinocarveol [5], and campholenic aldehyde, which are used to synthesize fragrances and formulate
perfumes. Campholenic aldehyde is used to produce compounds with sandalwood scents (sandalore, brahmanol, bogdanol, etc.)
and can be obtained in 85.0% yield from isomerization of 2,3-epoxypinane in the presence of acidic catalysts, e.g., ZnCl [6, 7].
2
Fencholenic (iso-campholenic) aldehyde was first reported in 1961 [8] and is also of interest for preparing new
fragrances. However, its fraction is usually small in the product mixture from isomerization of 2,3-epoxypinane. For example,
isomerization of 2,3-epoxypinane in the presence of montmorillonite clays K-10, Filtrol-105, and Tonsil LF-80 gave fencholenic
aldehyde in 11–19% yield in a mixture with campholenic aldehyde (27–40%) and other isomerization products [9]. Pinocarveol,
a difficultly accessible starting compound, was used to synthesize fencholenic aldehyde [10].
OH
O
O
3
4
5
O
O
OH
2
1
7
OH
O
OH
8
9
6
1) Institute of the Chemistry of New Materials, National Academy of Sciences of Belarus, 36 F. Skoriny St., Minsk,
220141, e-mail: evk@ichnm.basnet.by; 2) Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus,
5 Kuprevicha St., Minsk, 220141. Translated from Khimiya Prirodnykh Soedinenii, No. 5, September–October, 2018,
pp. 758–761. Original article submitted May 2, 2018.
©
0009-3130/18/5405-0893 2018 Springer Science+Business Media, LLC
893

TABLE 1. Contents of α-Pinene Epoxide Isomerization Products at 30°C in Cyclohexane over Clays Dried at 150°C for 2–4 h, %
Reaction time,
Clay
Unident.
2
3
4
5
6
7
8
9
min
K-10
K-30
L-1
IL-RS
Halloysite
10
10
30
15
30
14.8
14.2
13.8
13.1
15.0
0.5
0.3
1.2
0.9
0.4
40.4
41.0
40.1
38.0
40.6
21.0
20.8
28.0
27.9
18.7
9.9
9.4
7.3
8.8
11.2
3.0
3.1
2.5
2.9
2.8
5.8
6.2
4.3
4.8
5.9
2.5
2.6
1.4
1.4
1.8
2.0
2.3
1.3
2.1
3.5
TABLE 2. Contents of Aldehydes 4 and 5 in α-Pinene Epoxide Isomerization Products in the Presence of Illite Clay L-1, %
Solvent
Reaction time, min
– ratio
4 5
4
5
Toluene
Benzene
Cyclohexane
CH2Cl2
10
30
30
30
240
34.6
43.6
40.1
41.0
16.4
16.2
10.5
28.0
11.2
11.1
2.1:1
4.2:1
1.4:1
3.7:1
1.5:1
-Decane*
n
______
*43.4% conversion of α-pinene epoxide.
The goals of the present work were to optimize the conditions for isomerizing α-pinene epoxide into iso-campholenic
aldehyde and to develop a method for isolating it from the reaction mixture.
α-Pinene epoxide (1) was isomerized at 30°C in the presence of clay (3.0%) as a catalyst. Illite clays, sepiolite, and
glauconite were treated beforehand with HCl solution (10%), rinsed to remove traces of HCl, and dried at 50–200°C to
increase their activity [11]. The solvents were cyclohexane, decane, toluene, benzene, and CH Cl . Compositions of reaction
2
2
mixtures were determined by GC. Acomplicated reaction-product mixture was formed over all studied clays for isomerization
of 1. The main products were campholenic (4, up to 41%) and iso-campholenic aldehydes (5, up to 28.0%) (Table 1). Besides
them, the product mixture included trans-carveol (2, 13.1–15.0%), trans-sorberol (6, 7.3–11.2%), and small amounts of
pinocarveol (3) and iso-pinocamphone (7). p-Cymene (8) and pinol (9) were secondary isomerization products of
2,3-epoxypinane and were formed by dehydration of hydroxylated products [4].
Isomerization of α-pinene epoxide (1) was complete (99.9% conversion) after 10–30 min over montmorillonites
K-10 and K-30 and illites L-1, IL-RS, and halloysite (Table 1). The conversion was incomplete even after reacting for 4 h for
montmorillonite KSF, sepiolite, and glauconite. The contents of campholenic aldehyde (4) in the isomerization products were
about equal. However, the greatest amounts of iso-campholenic aldehyde formed over clays L-1 and IL-RS (Table 1).
Isomerization over clay L-1 of α-pinene epoxide in benzene, toluene, and CH Cl gave significantly lower amounts
2
2
of iso-campholenic aldehyde (5) in the product mixture than if cyclohexane was used (Table 2). The ratio of the amounts of
campholenic–iso-campholenic aldehydes (1.5:1) in n-decane was close to that in cyclohexane (1.4:1). Thus, a nonpolar
solvent enhanced the formation of iso-campholenic aldehyde.
Increasing the preliminary drying temperature of clay L-1 increased the content of 4 and decreased that of 5 in the
reaction mixture. Thus, practically equal amounts of the aldehydes (33–35%) formed on catalyst dried at 50°C. The content
of iso-campholenic aldehyde decreased to 25% if the drying temperature was increased to 200°C. The yield of fencholenic
aldehyde on illite IL-RS heat-treated at 50°C was 32%.
Bronsted and Lewis acids are known to catalyze isomerization of α-pinene epoxide [4]. Acidic hydroxyls,
coordinatively unsaturated and exchangeable catalyst cations, and polarized water molecules in the clay can act as such
centers [12]. Recently, the yield of iso-campholenic aldehyde was shown by us to increase if the acidity was decreased and
the ratio of Lewis–Bronsted centers in the clays was increased [11]. The proton-donating properties of water molecules
3+
3+
associated with exchangeable cations (primarily Al ) and Al cations on faces of tetrahedral layers of the clay minerals
increased with decreasing degree of hydration, i.e., with increased drying temperature [12]. However, the amount of
iso-campholenic aldehyde (5) decreased with increasing drying temperature for the illite clays. It could be proposed that
α-pinene epoxide isomerized into iso-campholenic aldehyde in the presence of polarized water molecules located on
the surface of the illite clay, i.e., weak Bronsted centers.
894

Obviously, the first step of the isomerization was reaction of a proton with the α-pinene epoxide oxirane ring to open
1
7
2
it and form carbocation A. Rearrangement of A on the clays could occur via migration of the C –C bond to cationic C to
2
3
form ion B. Cleavage of the C –C bond in cation B and subsequent loss of a proton formed campholenic aldehyde 4. An
1
6
2
alternative pathway for conversion of A is shifting of the C –C bond to C to form carbocation C, which rearranged similarly
to B to give iso-campholenic aldehyde 5. The A→B,C conversion in the presence of illite clay dried at 50°C occurred with the
same rate. Pathway A→B began to dominate if the drying temperature was increased to 200°C and the strength of the acidic
center increased because the strong Bronsted acidic centers enhanced formation of 4 [11].
OH
+
3
-H
C-C
1
5
O
3
O
+
OH
+H
1
B
4
7
OH
5
+
A
1
-H
1
5
C-C
3
O
5
C
Thus, isomerization of 1 into 5 was more effective in cyclohexane over weakly acidic illite clay catalysts.
The product yields were up to 33%.
A method for separating 5 from the reaction mixture was developed. An aldehyde fraction containing 90%
iso-campholenic aldehyde and 2% campholenic aldehyde could be separated from the other products.
The structures of the isomeric aldehydes were established using convergent synthesis of 4 according to the literature
method of Arbuzov [7]. The compound had physicochemical properties (IR, PMR, and mass spectra) that agreed with
the literature so it was used as a reference for spectra of 4 and 5 isolated from the isomerization reaction products. Also,
a convergent synthesis of 5 via isomerization of 2,3-epoxypinane (1) in the presence of BF ⋅Et O according to the literature
3
2
was attempted [13]. However, 4 was formed in 46% yield in this instance and had physicochemical properties identical to
those of campholenic aldehyde synthesized by the literature method [7].
PMR spectra of isomeric aldehydes 4 and 5 differed considerably with respect to the chemical shift of the H atom on
the ring double bond. Thus, H-3 of iso-campholenic aldehyde (5) was shielded by three methyls and had chemical shift δ 5.13 ppm
in the PMR spectrum. This differed by 0.1 ppm from the chemical shift δ 5.23 ppm of the less shielded H atom of 4. The
chemical shifts of the aldehyde H atoms were the same for the isomers. The methyl resonances differed by 0.03–0.05 ppm;
3
geminal protons H-5 and the chain, by 0.01–0.05 ppm. The vicinal SSCC J of H-4 with the neighboring H-5 ring protons in
4
4 and the J constant of H-3 in 5 were <1 Hz.
13
C NMR spectra of 4 and 5 showed considerably different resonances for all three methyls and C-3, C-4, and C-5 of
the cyclopentane ring. However, this did not allow any definite conclusions about the structures of the isomers to be drawn.
Two-dimensional NMR spectroscopy was used to establish unambiguously the spectral and structural correlations of
the isomeric aldehydes. Final conclusions were made based on an analysis of NOESY and HMBC spectra because COSY
spectra gave ambiguous assignments. Cross peaks of a proton and methyl on the double bond with the C-5 protons were
observed for both isomers without coupling to the C-1 proton. The most informative difference between the isomers in the
HMBC spectra was a cross peak between the C-2 methyl protons and the methine C atom (135.77 ppm) in 5. These protons in
4 coupled with quaternary C-3 (148.12 ppm). C-3 in the NOESY spectrum of 5 had cross peaks with all methyl protons
whereas the C-4 proton in 4 coupled with the C-3 methyl protons and the C-5 methylene protons. Based on these results, it was
considered proved that the methyl of 4 was situated on C-3; of 5, on C-4.
Thus, isomerization of 2,3-epoxypinane (1) in the presence of BF ⋅Et O according to the literature method [13] gave
3
2
campholenic aldehyde (4). As a result, the method described by us for preparing iso-campholenic aldehyde was more effective.
EXPERIMENTAL
The isomerization catalysts for α-pinene epoxide (Sigma-Aldrich, 98%) were commercial montmorillonites (K-10,
K-30, Al-Pillared Mont., KSF), sepiolite and halloysite (Sigma-Aldrich), natural illites L-1 (Belarus) and IL-RS (Russia), and
Belarusian glauconite from Loev deposit. The catalytic activity of the clays, except for K10, K-30, andAl-Pillared Mont., was
increased by treatment with HCl (10%, 5 mL/g) at 90°C for 3 h, rinsing thoroughly to remove acid, and drying at 50–200°C.
895

The quantitative composition of the reaction mixture was determined by GC using a Khromos GKh-1000 chromatograph with
a flame-ionization detector and Zebron ZB-5 capillary column (30 m × 0.25 mm 0.25 μm) and the literature method [11].
–1
IR spectra were taken from films on a Bruker Tensor 27 FT-IR spectrometer in the range 400–4000 cm . PMR and
13
C NMR spectra were recorded on an Avance 500 spectrometer (Bruker BioSpin) at operating frequency 500.0 and
1
13
125.7 MHz for H and C, respectively, using a Z-gradient 5-mm broad-band observe (BBO) probe. Spectra were recorded
13
from CDCl solutions with residual solvent resonances [δ 7.26 (1H, CDCl ); 77.16 ( CDCl )] as internal standards. Correlation
3
3
3
spectra (HSQC, COSY, HMBC, NOESY) were recorded and processed using standard software (Bruker BioSpin). Spin–spin
coupling constants (SSCCs) were given in Hz; chemical shifts, in ppm on the δ scale. Chromatographic analysis and mass
spectral measurements used a Thermo Scientific Trace GC Ultra/DSQ II quadrupole GC-MS with direct sample introduction.
Elemental analysis was performed on a vario MICRO element (CHNS) analyzer.
Isomerization of α-Pinene Epoxide (1). Compound 1 (2.0 g) was treated with solvent (total mixture volume of
20 mL), heated to 30°C, treated with catalyst (0.06 g, 3.0%), and stirred. The composition of the reaction mixture was
monitored using GC. The solvents were dry cyclohexane, n-decane, toluene, benzene, and CH Cl .
2
2
Isolation of iso-Campholenic Aldehyde (5). The mixture (20 mL) of α-pinene epoxide isomerization products
containing 35% campholenic aldehyde (4) and 33% iso-campholenic aldehyde (5) according to GC data was filtered to remove
clay. The solvent was evaporated to produce a transparent oil (2 g) that was treated with H O (3 mL) and dropwise with an
2
aqueous solution of sodium metabisulfite (Na S O , 2 g, 0.01 mol). The suspension was stirred for 2 h. Side products from
2
2 5
the isomerization were extracted by petroleum ether (2 × 10 mL) and EtOAc (3 × 10 mL) and discarded. The aqueous layer
was made basic using saturated aqueous Na CO solution to pH 8 and stirred for 1 h. Products were extracted by petroleum
2
3
ether (2 × 10 mL) and EtOAc (2 × 10 mL). The solvent was evaporated to afford a transparent oil (0.48 g, 24% yield) with a
pine scent that contained 89–90% iso-campholenic and ~2% campholenic aldehyde according to GC data.
2-(2,2,3-Trimethylcyclopent-3-en-1-yl)acetaldehyde (campholenic aldehyde) (4) was prepared by the literature
method [7]. α-Pinene epoxide (2 g) in anhydrous benzene (5 mL) was treated with ZnCl (0.2 g), heated on an oil bath at 80°C
2
for 20 min, and evaporated to give a transparent colorless oil (2 g) containing 80–84% campholenic aldehyde according to GC
data. The reaction product was purified by fractional vacuum distillation [bp 120°C (10 mm)] to afford a colorless oil (1.4 g,
–1
70% yield) that contained 92% campholenic aldehyde. IR spectrum (KBr, ν, cm ): 3441, 2957–2928, 1725 (Ñ=Î), 1629
1
(Ñ=Ñ), 1464, 1362. Í NMR spectrum (500 MHz, CDCl , δ, ppm, J/Hz): 0.79 (3Í, s, ÑÍ -2), 1.01 (3Í, s, ÑÍ -2), 1.62 (3Í,
3
3
3
s, ÑÍ -3), 1.88 (1Í, m, Í-5), 2.28 (1Í, dd, J = 4.3, 8.8, Í-1), 2.38 (2Í, m, Í-5, Í Ñ-ÑÍÎ), 2.52 (1Í, dd, J = 2.4, 15.6,
3
2
13
Í Ñ-ÑÍÎ), 5.23 (1Í, s, Í-4), 9.80 (1Í, s, ÑÍÎ). C NMR spectrum (125 MHz, CDCl , δ, ppm): 12.75 (ÑÍ , Ñ-3), 20.16
2
3
3
(ÑÍ , Ñ-2), 25.75 (ÑÍ , Ñ-2), 35.65 (ÑÍ , Ñ-5), 44.33 (ÑÍ, Ñ-1), 45.24 (ÑÍ , Ñ-ÑÍÎ), 47.05 (Ñ, Ñ-2), 121.69 (ÑÍ, Ñ-4),
3
3
2
2
+
148.12 (Ñ, Ñ-3), 203.21 (ÑÍ, ÑÍÎ). Mass spectrum, m/z (I , %): [M] 152.18 (4), 119.07 (6), 108.06 (100), 93.04 (87),
rel
81.03 (15), 67.02 (20), 41.02 (18). C H O.
10 16
2-(2,2,4-Trimethylcyclopent-3-en-1-yl)acetaldehyde (iso-campholenic aldehyde) (5), colorless oil. IR spectrum
–1
1
(KBr, ν, cm ): 3432, 2956–3025, 1725 (Ñ=Î), 1657 (Ñ=Ñ), 1447, 1361. Í NMR spectrum (500 MHz, CDCl , δ, ppm, J/Hz):
3
0.80 (3H, s, ÑÍ -2), 1.02 (3H, s, ÑÍ -2), 1.65 (3H, s, ÑÍ -4), 1.98 (1Í, dd, J = 15.4, 8.5, Í-5), 2.31 (1Í, m, Í-1), 2.35 (1Í,
3
3
3
13
m, Í Ñ-ÑÍÎ), 2.39 (1Í, m, Í-5), 2.51 (1Í, d, J = 14.9, Í Ñ-ÑÍÎ), 5.13 (1Í, s, Í-3), 9.78 (1Í, s, ÑÍÎ). C NMR spectrum
2
2
(125 MHz, CDCl , δ, ppm): 16.73 (ÑÍ , Ñ-4), 22.56 (ÑÍ , Ñ-2), 28.13 (ÑÍ , Ñ-2), 42.16 (ÑÍ , Ñ-5), 43.72 (ÍÑ, Ñ-1), 45.20
3
3
3
3
2
+
(ÑÍ , Ñ-ÑÍÎ), 46.35 (Ñ, Ñ-2), 135.77 (ÍÑ, Ñ-3), 136.79 (Ñ, Ñ-4), 203.17 (ÑÍ, ÍÑÎ). Mass spectrum, m/z (I , %): [M]
2
rel
152.06 (28), 137.04 (31), 119.05 (12), 108.07 (100), 95.06 (92), 93.02 (96), 90.99 (32), 81.02 (18), 76.97 (18), 67.01 (38),
40.98 (22). C H O.
10 16
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